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Dumitru 2nd Ed
Dumitru 2nd Ed
MEDICINE
Second Edition
LECTRODIAGNOSTIC
EDICINE
Second Edition
San Antonio.Texas
ANTHONY A. AMATO, MD
Associate Professor
Department of Neurology
Boston, Massachusetts
Institute of Neurology
Note to the reader: Although the infonnation in this book has been carefully reviewed for correctness of dosage and in
dications, neither the authors nor the publisher can accept any legal responsibility for any errors or omissions that may
be made. Neither the publisher nor the authors make any warranty, expressed or implied, with respect to the material
contained herein. Before prescribing any drug, the reader must review the manufacturer's current product infonnation
(package inserts) for accepted indications, absolute dosage recommendations, and other infonnation pertinent to the safe
and effective use of the product described.
1. Electrodiagnosis. I. Dumitru, Daniel. II. Zwarts, Machiel J., 1953- III. Amato,
Anthony A., 1960
[DNLM: L Electrodiagnosis-methods. 2. Nervous System Physiology. 3.
RC71.DS7 200 1
616.07'547-dc 21
2001026407
© 2002 by Hanley & Belfus, Inc. All rights reserved. No part of this book may be reproduced, reused, republished, or
transmitted in any fonn, or stored in a data base or retrieval system, without written pennission of the publisher.
You never know when happiness might rise. mysterious and black.
called Comfort, a small park with a white Then his sister comes along.
that it's almost spring. A bit breezy Two cats now sit beneath
I am extremely grateful to my mentors and good friends, Jerry Mendell, M.D., John Kissel,
M.D., Zarife Sahenk, M.D., and Richard Barohn M.D., who taught me the art of evaluating and
treating patients with neuromuscular disorders.
AAA
lowe gratitude to my colleagues, and the technicians and secretaries of the department of
Clinical Neurophysiology and the physics-technical group for their support and inspiration. The
cooperation of the neurologists and other members of the Neuromuscular Centre Nijmegen is
greatly appreciated.
MZ
Contents
Part I FUNDAMENTAL PRINCIPLES
Nerve and Muscle Anatomy and Physiology ...................... 3
Daniel Dumitru, M.D., Ph.D., and Andrew J. Gitter, M.D.
3 Instrumentation ............................................ . 69
Daniel Dumitru, M.D., Ph.D., and Machiel J. Zwarts, M.D., Ph.D.
vii
viii - CONTENTS
Generation
Index 1489
x
Preface
Welcome to the second edition of Electrodiagnostic Medicine. I am gratified that the first edi
tion was very well received by the electrodiagnostic medicine community worldwide. Every effort
has been made for the second edition to continue in the same tradition of excellence.
Perhaps one of the most significant changes in the second edition is the addition of an interac
tive cross-platform (PC or Mac) CD ROM. The CD contains the Needle Electromyography chapter
found in this textbook with links to specific waveforms described in the text. After reading about
the waveform, one can simply click on the linked waveform to play it. It is also possible to play
each of the waveforms in any sequence independent of the text. The waveforms are needle elec
tromyographic recordings from patients examined by the editors with a narrated description of the
waveforms' pertinent electrophysiologic findings. Essentially any waveform, normal or patho
logic, likely to be encountered in clinical practice is represented, in addition to several artifact
recordings. If the practitioner has a PC-based electrodiagnostic instrument, it is possible to down
load the CD onto the instrument and compare those waveforms recorded from one's patients with
those on the CD.
Another major addition to the textbook is a more detailed assessment of the individual disor
ders' histopathology, molecular biology, and genetics. The most current information available re
garding the multitude of diseases described within the book is included replete with numerous
references. As in the first edition, an emphasis is placed on corresponding figures and tables to aid
in the understanding of disease pathophysiology. Every chapter in the text was continually updated
up to the point of publication.
In this edition, two additional editors have joined me to bring a more complete perspective to
electrodiagnostic medicine. Anthony A. Amato, M.D., contributed his expertise in neuromuscular
disorders to ensure that the genetic and molecular biology aspects of the diseases discussed are ac
curate and up to date. Machiel Zwarts, M.D., Ph.D., ensured that the information contained in the
text was comprehensively addressed from a clinical neurophysiology standpoint and added a
European perspective on the electrophysiologic diagnosis of neuromuscular disorders. Further,
several new chapter authors have been added to ensure that a broad approach to neuromuscular
disease is presented to the practitioner.
Considerable effort has been made to ensure that the textbook, while broad in scope, remains
practical and readable. Although the book has clearly developed into a major reference text, it is
still possible to read it from cover to cover. This is due in large part to significant editing to ensure
a uniform writing style irrespective of multiple authors. As with the first edition, an emphasis re
mains on the complete description of a disorder in plain language supported by figures and infor
mative tables. It is my contention that the patient cannot truly be served unless the practitioner
acquires a thorough understanding of a disorder. The second edition of Electrodiagnostic Medicine
continues in the tradition of the first edition in providing the practitioner with the most comprehen
sive information and literature citations available in the field.
xl
PART
FUNDAMENTAL
PRINCIPLES
Chapter I
and Physiology
CHAPTEROUTUNE
Muscle Tissue
The Membrane Potential Muscular Components • Electrical Activity
Membrane Potential Generation • Nerve Cells • Action
Potential • Action Potential Propagation Conclusion
The practice of electrodiagnostic medicine requires knowl substance has a (1) polar or hydrophilic ("water-loving") aspect
edge of nerve and muscle physiology. During the course of an and a (2) nonpolar or hydrophobic ("water-fearing") part. Most
electrodiagnostic medicine examination, the practitioner inves plasma membrane phospholipids have a polar head group attached
tigates either directly or indirectly nerve and muscle action po to two nonpolar tail moieties (Fig. 1-1). If amphipathic lipid mole
tentials. This chapter reviews the basic principles of cell cules are placed in a water solution, they spontaneously coalesce
membranes, membrane potentials, action potential generation so that the nonpolar tail groups form an interior compartment ex
and propagation, nerve-muscle interaction, and muscle physiol cluding water, thereby exposing the polar head groups to the water
ogy. Understanding normal function allows greater appreciation environment.43 Two self-sealing lipid arrangements may occur.
and insight into the pathophysiologic processes and electrodiag The first is a spherical micelle, which forms when the lipid tails
nostic manifestations of nerve and muscle disease. congregate within a sphere and the polar groups face outward. The
second spontaneous lipid aggregate is a bilayer.
Lipid Bilayer. The outer cell membrane is a lipid bilayer, a
NERVOUS TISSUE dual sheet of phospholipid molecules aligned so that the hy
drophobic tails contact each other forming a nonpolar region
PLASMA MEMBRANE free of water. The polar head groups are exposed to the sur
rounding aqueous environment (Fig. I-1B). The usual width of
The plasma membrane forms the outer boundaries of the cell this structure in most cells approaches 75 angstroms (1 A =
thus defining intracellular and extracellular contents. It serves to: 10-10 meters {m}) and is known as a unit membrane. 62 The
(1) maintain the cell's integrity, (2) produce and sustain ion con lipid bilayer possesses a high degree of fluidity and may be
centration gradients and electric charge differences across the thought of as a two-dimensional liquid in which the lipid mole
cell, (3) control nutrition intake and waste disposal, and (4) assist cules have constrained mobility characteristics. First, a lipid
in the cell's interaction with its environment. All plasma mem molecule can rotate about its long axis very rapidly (Fig. I-IC).
branes share three basic structural molecules: lipids, proteins, Secondly, the lipid molecule can diffuse in a lateral direction. A
and carbohydrates. Lipid and protein each constitute approxi third, and rare occurrence, is for a lipid molecule to "flip-flop"
mately 45-49% with carbohydrate accounting for the remaining from one side of the bilayer to the other (Fig. 1-1C).I 5 Inter
2-10% of the cell membrane's molecular composition. 13 spersed within the bilayer are cholesterol molecules that are be
There are three different types of lipids forming the plasma lieved to add stability to the bilayer. Glycolipids exist only on
membrane: phospholipids, cholesterol, and glycolipids. 62 These the outer surface of the bilayer covalently bound to carbohydrate;
three lipid molecules are amphipatbic. 13•23 An amphipathic their true r:nction is not fully understood. Cholesterol, present
3
4 - PART I FUNDAMENTAL PRINCIPLES
Phospholipid Fluid mosaic structure passing through the hydrophobic region. Two types of trans
membrane or transport proteins are used to facilitate move
choline
ment of these substances through the plasma membrane. 3,49
glycerol
1 Channel proteins extend across the lipid bilayer and have a
water-filled central tunnel or pore that allows the passage of spe
folty OCld
cific ions or molecules (Fig. 1-2). A second type of transport pro
tein, carrier protein, binds the substance to be transported and
undergoes a conformational change to effect transmembrane
crossing. These protein transport mechanisms are selective for the
A B particular ion or molecule to be delivered across the membrane.
lipid mobility Substances can pass through the cell membrane by either dif
translational movement flip'flop~
fusion or active transport.22 Diffusion is the movement of in
~-m~
dividual molecules driven by the thermal and kinetic energy of
matter's random movement, either directly through the inter
c molecular spaces of the plasma membrane's lipid portion, or in
conjunction with a channel or carrier protein. Active transport
requires an energy source other than kinetic energy to move a
Figure I-I. The Plasma Membrane. A, Molecular model of a
substance across the plasma membrane "uphill" against an
phospholipid molecule (phosphatidylcholine) consisting of a hy
energy gradient, e.g., from low to high ion concentration.22
drophilic "head" group (choline and glycerol) and a hydrophobic "tail"
portion (fatty acid). Phosphatidylcholine is only one of many possible Diffusion
phospholipids. B, Representation of the fluid mosaic model of the
An ion or molecule may cross the cellular membrane by
plasma membrane. A lipid bilayer is pictured with membranous and
either simple diffusion or facilitated diffusion (Fig. 1-2). In
trans membranous proteins. C, Translational and flip-flop degrees of
simple diffusion a substance crosses the plasma membrane rely
freedom available to the phospholipid molecule in the bilayer. (From
ing solely upon thermal-induced random kinetic motion without
Barchi RL: Excitation and conduction in nerve. In Sumner AJ (ed):The
the need for carrier proteins. The rate of simple diffusion de
Physiology of Peripheral Nerve Disease. Philadelphia, WB. Saunders,
pends on the (1) kinetic energy present in the system, (2)
1980, pp 1-40, with permiSSion.)
number of openings (channel proteins) in the membrane avail
able to the ion or molecule, and (3) how much of the substance
within the bilayer increases the plasma membrane's stability as is present, Le., the concentration gradient across the membrane
wen as reduces permeability to small water-soluble molecules. for a particular substance. 22 Facilitated diffusion, however, re
quires that the molecule or ion first bind a carrier protein prior
TRANSPORTTHROUGH THE CELL MEMBRANE to passing through the membrane.
Simple Diffusion. Simple diffusion allows substances to cross
While the lipid bilayer provides structure for the cell mem through the cell membrane by either passing through the lipid bi
brane, proteins imbedded in, or projecting through, the bilayer layer directly or by using a transmembrane protein channeL It is
carry out the active processes necessary for the cell to function. 62 possible to measure the transport properties of the lipid bilayer by
in order for the cell to function, a wide variety of substances rang removing the membrane proteins. The primary factor that deter
Ing from simple ions to complex glycoproteins must pass through mines the ease with which a substance moves through the bilayer
the plasma membrane. Lipid-soluble molecules can enter or exit is its lipid solubility. Molecules such as oxygen, nitrogen, and
the cell directly across the cell membrane. The lipid bilayer, how carbon dioxide are highly lipid-soluble and pass directly through
ever, prevents relatively large water-soluble molecules from the cell membrane without difficulty. Although water is not
highly lipid-soluble, it penetrates the lipid bilayer relatively easily
because of its small size and high kinetic energy.20 It is possible,
therefore, for small molecules with a low lipid solubility to cross
Channel the cell membrane. As a molecule's size increases, its ability to
I protein diffuse in or out of the cell diminishes markedly (Table 1-1).22
ImH(S~ I~
\~~/ ::~:ng
Substance Diameter (nm) Relative Permeability
Water molecule 0.30 1.0
~ '---~.:-
I
Urea molecule 0.36
Hydrated chloride ion 0.386
0.0006
0.00000001
~\~
'~¥W
.. M
W~V
Hydrated potassium ion 0.396 0.0000000006
Hydrated sodium ion 0.512 0.0000000002
/ conformational
Glycerol 0.62 0.0006
ooV~
change
Glucose 0.86 0.000009
As an example, consider the glial cell described previously. Table 1·2. Cellular Ionic Concentrations and Equilibrium
For an ion such as K+ with a charge of 1+, the valance value Z = Potentials
1+. At a temp of 20°C, the quantity RTIZF reduces to 26 milli Intracellular Extracellular Equilibrium
volts (mV). In vivo, the glial cell exists in an environment with (mmoIlL) (mmoIlL) Potential (mY)
intracellular K+ concentration approximately 20 times greater
than the extracellular K+ concentration. Under these conditions, Squid Axon
the Nernst equation would predict a transmembrane equilibrium Na+ 50 440 +55
potential of: K+ 400 20 -76
CI 52 560 -66
Em =-(26 mY) (In 2? )=-16 mV Organic anions 385
Mammalian Axon
In this example, maintenance of the equilibrium potential de Na+ 10 145 +56
pends only upon the passive electrical and diffusion forces and K+ 160 4 -102
does not require additional energy other than thermal energy Cr 3 114 -76
driving diffusion. This can be appreciated by considering an ex anions 163 34
periment in which a microelectrode is inserted into the glial cell
so that it does not disrupt the plasma membrane or other cellular
mechanisms. Suppose a small positive current is injected into the cell membrane at equilibrium is much more permeable to
the cell partially depolarizing it, i.e., the intracellular space be K+ than Na+ with an intermediate permeability to Cl-.30
comes less negative than the resting potential. The negative The consequences of having multiple ions contribute to the
electrical force preventing potassium ion efflux is reduced and eqUilibrium potential is more complex but the same basic prin
potassium ions diffuse out of the cell toward the low K+ concen ciples outlined by the Nerst equation apply.3o.31 As previously
tration extracellular space. Potassium leaves the cell until described for K+ ions, each ion species has its own unique equi
enough positive potassium cations are lost to balance the posi librium potential that depends on that ion's concentration inside
tive charge injected and return the transmembrane potential to and outside the cell. A nerve axon's equilibrium potential is pro
-16 mV. Now, suppose the cell is hyperpolarized (i.e. the intra portional to not only K+, but also Na+ and CI-.
cellular space becomes more negative than the resting potential If the cell membrane were permeable only to Na+ ions (this
of -16mV) by injecting negative charges into the cell. The in can be accomplished by blocking other ion channels with neu
crease in electrical negativity inside the cell creates an electrical rotoxins) a resting equiHbrium potential of + 55 mV would be
force that attracts potassium ions from the extracel1ular space. generated. This reflects the diffusion and electrical forces acting
Potassium ions diffuse into the cell through the ion channels on the sodium ion in a manner analogous to the potassium ion.
until transmembrane potential is once again restored to the equi Because of the steep concentration gradient of Na+ from a
librium level of - 16mV. The equilibrium potential is the electri
cal potential (voltage) across the cell membrane at which the
force driving potassium ions from a high intracellular to low ex \
-80 \
tracellular concentration is just balanced by an inward electrical \
\
force acting on the positive potassium ion. -70 \
\
\
\
NERVE CELLS ">E \
- -50 \ 4°C
Using the Nernst equation to predict the resting membrane ,g \
\
potential of nerve cells, Julius Bernstein in 1902 suggested a ~ -40 \
nerve's resting membrane potential depended upon the selec \
&. ~
tive permeability of K+.8 This prediction would require that the !! - 30
transmembrane potential of neural tissue varies directly with
changes in the intra/extracellular concentration of K+. For glial i~
-20
higher extracellular to a low intracellular concentration, diffu phosphate bonds of ATP to maintain the ion concentration gra
sion forces drive Na+ into the cell (Table 1-2). As the Na+ dients across the plasma membrane. The Na+- K+-ATP pump
cations diffuse into the cell and accumulate, the inside of the imports 2 potassium ions for every 3 sodium ions it exports to
cell becomes positively charged, repelling further Na+ entry. the extracellular region. Due to the unequal transport of ions
The competing effects of electrical and diffusion forces on Na+ across the cell membrane (more positive charges exported than
ion flow are balanced at the transmembrane potential of + 55 imported), the pump generates a small electrogenic offset that
mV. The opposite polarity of the transmembrane potential for lowers the resting membrane potential several millivolts below
Na+ compared to K+ reflects the opposite concentration gradi that predicted by the Goldman-Hodgkin-Katz equation.
ents for these ions. Unlike the K+ and Na+ ions, the chloride anion is not subject
IYpically nerve cells have a resting potential that is approxi to active transport, but is free to be distributed by purely passive
mately 60-70 m V negative intracellularly, placing the actual forces. Chloride anions are by default in equilibrium with re
membrane potential in between the individual ion membrane spect to the axon's membrane. The actual transmembrane con
potentials. At this resting membrane potential, the potassium centrations of CI- are determined by the resting membrane
ion is close to its equilibrium voltage, while the sodium ion is potential and are adjusted accordingly. As a result, Na+ and K+
more than 100 mV from achieving its equilibrium potential. As are actively distributed, whereas Cl- is passively distributed.
a result, there remains a strong electrical gradient, in addition to
the concentration gradient, that favors Na+ movement into the ACTION POTENTIAL
cell. The Na+ that diffuses into the cell under these conditions
has the same effect as the injected current in the above-noted One of the fundamental purposes of the nervous system is
experiment, i.e., the membrane potential deviates from the communication, both within an organism as well as between the
potassium eqUilibrium potential toward the sodium ion's equi organism and its environment. The nervous system has devel
librium potential (a less negative value). The loss of some of the oped a relatively simple yet highly efficient means of relaying
negative intracellular potential allows some potassium to exit information and reacting to stimuli by means of electrical im
the cell. This exiting positive potassium charge acts to balance pulses. These self-sustaining impulses are based on ion perme
the influx of positive sodium ions. A new equilibrium potential ability shifts and are known as action potentials. In 1849 the
(e.g., - 60 mY) is achieved at which the K+ efflux equals the German physiologist Emil DuBois-Reymond first described the
Na+ influx. The resting membrane potential is not halfway be production of action potentials by axons.40 It has taken approxi
tween the two ions' equilibrium potential because the mem mately 130 years to begin to appreciate the molecular mecha
brane is not equally permeable to both ions; it is much more nisms responsible for the generation and propagation of action
permeable to potassium, and therefore closer to the potassium potentials.
equilibrium potential. Permeability depends on the number of Ionic Hypothesis. K. S. Cole and H. J. Curtis in 1938 pro
channels available for a particular ion. The resting membrane duced action potentials in squid axons while performing intra
potential determined by the simultaneous effects of K+, Na+, cellular recordings. '2 The squid axon was used because it was
and Cl- ions was first described by Goldman and depends on the large enough to allow the intra-axonal placement of the rela
ion's permeability (p) and the transmembrane ion concentra tively large recording electrodes available at the time. These
tions. The relationship dictating the resting membrane potential
is referred to as the Goldman-Hodgkin-Katz equation: 21 INSIDE Membrane OUTSIDE
15
u
Em = RT In (PK[K:Ji + PN.[Na:1i + Po [CI-le) E
<I>
F PKlK le PNa[Na]e PdCI-]i K+
.c.
u
~ "2
From this equation, it can be seen that the membrane poten t; C
<I>
J!
tial is influenced heavily by the most permeable ion. For nerve <I>
8.
and muscle, the resting membrane potential is closest to K+, the ~a
most permeable ion. s:
Because the resting membrane potential of the cell is not the +
same as either the Na+ or K+ equilibrium potentials, a small Na+ No
ion influx balanced by K+ ion efflux is constantly occurring. 15
Without a cellular mechanism to compensate for this, the intra u
...
.,c_ ·9r-
J f
the cell membrane increased its ionic conductance. This finding A
established that the action potential is directly dependent upon .c'=>
the transmembrane movement of ions. Determining the exact .--
e;e
.'fli
56 mV Oeool.ril.Cion
1
ion(s) involved in action potential generation began with the -65~
work of Hodgkin and Katz, who noted a reduction in the squid
axon's action potential magnitude if the Na+ concentration of
the solution bathing the axon was reduced.25 Combining the in B
solution i
C In -I
•
amount of current injected can be regulated to match the current ..•
~ o 3
flow caused by ion movement across the cell membrane. The
end result is the ability to directly record the amount of current
.
c
.l;
rome Imsl
:i
was abruptly changed from its resting potential of - 65 m V to
-9 mV and held there with the voltage clamp (Fig. I-8A). To
D Out I
maintain the transmembrane potential at - 9 m V, the voltage
clamp injected a biphasic current into the cell. During the first Calculated
between
tial, the voltage clamp needed to inject negative charges into the BandC
of TEA
I
exists that the action potential is mediated by abrupt changes in
. ion flow controlled by specific membrane channels for Na+ and
r
~
K+. The opening and closing of these Na+ and K+ channels
depend on the transmembrane voltage, i.e., the channels are
voltage-gated. Experimental studies using patch-clamp tech
niques that isolate small patches of the cell membrane surface
EK have demonstrated that an unmyelinated nerve has approxi
mately 5-500 Na+ channels per square micrometer (flm 2) of
membrane, which are open for approximately 0.7 ms during the
course of an action potentia1.50.51.60 The channel is either fully
opened or fully closed with no intermediate states of partial
opening. Radioactively labeling tetrodotoxin and applying it to
a nerve membrane has confirmed the density of Na+ channels.58
The voltage-gated Na+ and K+ channels are separate from
o 2 4 each other and different from the passive Na+ and K+ "leak"
TIME rna channels that are responsible for the resting steady-state mem
o 25 !SO 7S brane potential. Although individual voltage-gated channels
DISTANCE (mm) have not been directly visualized, their functional subcompo
nents have been identified and their role in the process of gener
Figure 1-9. Action potential.Action potential produced by the
ating an action potential has been well established. The
depolarization of a giant squid axon. Note that the Na+ channels are
potassium ion channel appears to exist in two voltage-depen
first open for less than I ms (see time scale at bottom) and produce
dent conformational states, an open or activated state and a
the initial rise of the action potential. The Na+ channels then close and
closed or deactivated state. The physical site of the activation
the delayed opening of the K+ channels influences the action potential
gate remains uncertain, but it is believed to be located within the
and produces its decline back toward the resting membrane potential.
ion channel pore near the extracellular opening. Sodium chan
Because the K+ channels stay open slightly longer than that required
nels have a similar activation gate, but display greater electro
to reach the previous resting level. the cell is slightly hyperpolarized.
physiologic complexity that indicates they also exist in a third
The local currents (inward flow of only Na+) are shown and extend
conformational state in which the channel is inactivated and
over a distance close to 30 mm. (From Hille B: Introduction to physiol
not permeable even though the activation gate may be open.
ogy of excitable cells. In Patton HD, Fuchs AF, Hille B, et al (eds):
This can be accomplished by the inclusion of a separate inacti
Textbook of Physiology. 21 st ed. Philadelphia, W.B. Saunders, 1989, pp
vation gate, typically conceptualized as a ball and chain or
1-80. with permission.)
hinged lid that blocks ion flow by occluding the inner opening
of the channel.
there is a brief initial inward flow of positive ions followed by a Variations in conformation states and the temporal character
delayed sustained outward flow of positive ions (Fig. 1-8B). istics of channel opening and closing underlie the generation of
If the solution bathing the cell is replaced with one devoid of the action potential. Initially, the nerve is in a resting state with
Na+ but does contain an impermeable cation such as choline, the a membrane potential of - 90 mV (mammalian nerves). Na+ and
inward-directed positive current no longer occurs (Fig. I-8C). K+ ions are passively diffusing across the membrane in their 3:2
The outward positive current, however, remains unchanged. This ratio balanced by the electrogenic Na+-K+-ATP pump creating a
result implies that Na+ mediates the inward but not the outward resting steady state (individual ions moving across the cell
current. By manipulating ion concentrations and substituting membrane, but no net change in charge). The voltage-gated Na+
ions species in the bathing solutions, Hodgkin and Huxley and K+ channels are closed (Fig. 1-10). If the transmembrane
demonstrated that depolarization triggers an initial short-lived voltage is reduced by 15-20 m V toward a threshold value of
inward Na+ current and a somewhat delayed and prolonged out approximately 65 to - 70 mV, the voltage-gated Na+ channel
ward K+ current (Fig. 1-8C, 1-8D). The action potential, then, is senses the threshold voltage change and rapidly undergoes a
a transient reversal of transmembrane potential producing an ini conformational change that activates and opens the Na+ channel
tial depolarization through an inward-directed Na+ ion flow, fol (Fig. 1-10). The membrane permeability to Na+ is increased by
lowed by a repolarizing outward-directed K+ current (Fig. 1-9). a factor of 5,000 times allowing rapid sodium entry into the
Tetrodotoxin, a purified poison from the puffer fish has been cell. 22 Approximately 1 ms later the Na+ gate becomes inacti
employed to confirm the results of Hodgkin and Huxley.58 vated and the rapid sodium influx is halted. During the interval
Tetrodotoxin specifically binds to the voltage-gated Na+ chan between activation and inactivation, the Na+ channel allows for
nel and blocks it from opening. This blockade allows investiga a transient flow of ions that shifts the cell membrane toward the
tors to eliminate the sodium current and directly investigate the Na+ eqUilibrium potential, depolarizing the membrane to a volt
various parameters of the potassium current. One may also age of approximately + 40 mV. Inactivation occurs through a
apply tetraethylammonium (TEA) to selectively "lock the K+ gating mechanism that is distinct from the action of the activation
Chapter I NERVE AND MUSCLE ANATOMY AND PHYSIOLOGY - II
~[p~
perpolarized state generated by the prolonged K+ channel
opening and the associated outward K+ ion flow.
The total number of intracellular potassium ions that leave
the cell during the generation of an action potential is small and
only reduces the intracellular concentration by approximately
0.03 to 0.0003 percent. 34 This concentration difference is most
Resting
likely not experimentally detectable. As the voltage-dependent
Activated (-90 to +35 mV
(-90mV) (-90 to +35 mV) delayed) gates open and close, ion permeability is dramatically altered
for a brief period but only a small number of ions pass through
the membrane relative to the size of the intracellular and extra
cellular ion pools. Relating this to the Goldman-Hodgkin-Katz
equation, it is the alterations in ion permeability or conductance
that cause the dramatic shifts in the transmembrane potential
rather than any significant ion concentration change (Fig. 1-9).
may help to determine ion selectivity and differences in gating ACTION POTENTIAL PROPAGATION
mechanisms between the various members of the voltage-gated
channel family.9 Passive Current Potentials
Gene cloning and mutagenesis studies are used to map the The ability of a membrane to abruptly depolarize in response
key function of ion selectivity, voltage sensing. activation, and to a threshold voltage change is an essential feature that allows
inactivation gating to structural subunits of the ion channel. for propagation of action potentials along a nerve or muscle
Although considerable understanding of ion channels exists, de fiber. Experimental studies using unmyelinated squid axons and
tails of the molecular shape, movement, and action that create microelectrode injection of depolarizing currents have been
the various functions are incompletely understood. The alpha used to define the events that lead to action potential conduc
subunit alone appears to be capable of forming a functional ion tion. When microelectrodes have been placed within the axon
channel displaying both selectivity and gating properties.
Connecting the S5 and S6 transmembrane segment is a peptide
chain named the H5 or P loop (Fig 1-11).9.46 The P loop is RESTING OPEN INACTIVATED
thought to project inward and line the water-filled central pore
of the ion channel. Resembling an hourglass, the central pore
has relatively inert hydrophobic characteristics except in the
narrow portion where the ion selectivity filter may be located
(Fig. 1-11 B). While the precise mechanism of ion selection is
unknown, filter characteristics include a physical size that
favors one particular ion over others and electrically charged
residues within the channel pore that stabilize appropriately
sized hydrated cations allowing them to pass through an other
wise hydrophobic channel,9·16,46
In generating an action potential, the voltage-gating mecha
nism creates a physical conformational change in response to a Figure I -12. The model for sodium channel activation and
threshold alteration in the transmembrane potential. This thresh inactivation. In response to membrane depolarization, S4 segments
old potential needs to be "sensed" by the ion channeL Experi move outward, reSUlting in opening of the channel pore. Inactivation
mental data indicate that voltage sensing is a function of the S4 occurs when the intracellular linker segment between domains 3 and 4
transmembrane segment, which has a unique repeating structure closes over the intracellular mouth of the pore, blocking the flow of
of lysine or arginine amino acid residues that are electrically ions. (From Ragsdale DS,Avoli M: Sodium channels as molecular targets
charged (Fig 1-11). In response to a threshold depolarization, for antiepileptic drugs. Brain Res Rev 1998;26: 16-28. with permission.)
Chapter 1 NERVE AND MUSCLE ANATOMY AND PHYSIOLOGY - 13
A ~ @
~
l5_
fY
,
~.o_
~
DISTANCE ( mm I
along its length, the magnitude of the resting membrane poten space. This process of current flow is known as a local cirenit
tial as one moves away from the site of stimulation can be current. This type of current flow is also seen in electrical cir
recorded. If a brief subthreshold positive current is injected into cuits that use capacitors (discussed below).
the axon, the sequentially located microelectrodes record an ex In addition to this capacitive local current flow,24.S6 a small
ponential decline in the transmembrane voltage with distance outward-directed current flows through open ion (mainly K+)
(Fig. 1_13).24 This decline in potential is known as an electro channels. Because only a limited number of potassium channels
tonic potential and results from a diminishing positive current are available, the membrane offers some resistance to this path
density the further one gets from the point of current injec of current flow. In unmyelinated axons, most of the current that
tion.24.29 As the injected current spreads away from the entry
site, it attempts to flow along the path of least resistance. In the l' .......................................... ..
case of the axon, the current essentially has two choices, to flow A
either down the length of the axon or through the plasma mem
brane into the extracellular space.
Positive charge introduced into a localized segment of an
axon, whether injected experimentally or due to Na+ influx from
the opening of an ion channel, creates a region that is more pos
itive or depolarized relative to adjacent segments. This extra
positive charge will flow longitudinally (moving charge is
called a current) into the more negative surrounding portions of
the axon through both intra-axonal and transmembrane routes.
c ()::::::::~:::::::. )
Transmembrane current flow begins as the positive charge ------------~--------- .
. . . . . . . . ++----+.+++ .....
spreading from the site of injection into more negative adjacent '..J' "-.../
~
regions balances (or neutralizes) an equivalent number of the .+--------- --------./"'.••
normally present intracellular negative charges that are main o --+.++++++.+.+++.~++--
"-.../
positive sodium ions aligned on the extracellular side of the
membrane is reduced (Fig. 1-14). The extracellular positive Na+ Figure 1·14. Local circuit current. Local circuit current demon
ions are then free to move away from the membrane. The result strating movement of positive charges into the excitable tissue and
is current flow without the need for ions to actually pass through then depolarizing adjacent regions of the fiber. (From Guyton AC:
the membrane. Positively charged ions moving intracellularly Textbook of Medical Physiology. 9th ed. Philadelphia. W.B. Saunders.
induce the flow of different positive ions in the extracellular 1996. pp 43-55. with permission.)
14 - PART 1 FUNDAMENTAL PRINCIPLES
is injected is carried away by local current transmembrane plate. Charge accumulates until the two plates have a voltage
mechanisms. The remaining current that did not exit though the difference equal to the battery, at which point equilibrium
membrane is free to proceed further down the axon into the next exists. If the voltage across the plates is suddenly changed, for
adjacent segment The same process of local circuit currents is example if the negative plate is suddenly made more positive,
repeated as intracellular anions are balanced and extracellular the loss of the negativity will reduce the electrical forces that at
Na+ is no longer as tightly bound to the immediate vicinity of tract and hold positive charges onto the other plate, freeing
the membrane and flows away. At each subsequent segment of some of them to flow away (Fig. 1-15). This is very similar to
membrane less current is available, making the magnitude of what occurs in axon membranes. Indeed the cell membrane ef
the transmembrane voltage change smaller and smaller as it fectively acts as a capacitor by separating intracellular negative
moves down the axon. The process repeats until there is no charges from extracellular positive charges. The inner portion of
longer any appreciable current the lipid bilayer is hydrophobic and nonpolar, which means that
The value of local current flow is that it allows transmem it does not conduct or hold a charge well, thereby serving as a
brane current flow without the need for open voltage-gated ion good insulator. The outer and inner surfaces of the membrane,
channels. Current flows across the membrane without ions actu however, are polar and charged, which means that they can act
ally passing through the membrane because the membrane acts as the plates of a capacitor to hold charge. An injection of posi
like an electrical device known as a capacitor. A capacitor is an tive charges into the cell allows current to flow by discharging
electronic device capable of storing and separating opposite po the membrane capacitor. This discharge occurs when positive
larity charges (Fig. 1-15).37 Simplified, a capacitor consists of charges are added to the inside of the membrane, allowing posi
two metal plates separated by an insulating material. If these tive charges to be removed from the outer membrane (Fig. 1
two plates arc connected to a voltage source such as a battery, 13). The relative electrical resistance of the various pathways
current initially flows onto the two plates. Positive charges ac for current flow dictates the preferential path of current flow:
cumulate on one of the plates and negative charges on the other transmembrane versus longitudinal flow. In unmyelinated axons
the intracellular resistance of the axoplasm is high because the
Out axon diameter is very small. As a result, current preferentially
A
discharges the membrane capacitor or flows through the mem
brane's aqueous "resistor" channels (a small effect). The net
result of current loss through adjacent sequential portions of
Current the membrane is a transmembrane potential difference that di
g enerator minishes exponentially down the length of the axon. This is
known as an electrotonically declining potential difference
(Fig. 1-13).
In
Active Currents in Unmyelinated Nerve
Suppose adequate positive current is injected into a nerve to
Out raise the transmembrane potential to threshold. Once threshold
B is reached, the voltage-gated Na+ channels open. The open
sodium channels allow positive Na+ ion charges to enter and
spread into adjacent segments of the axon's interior. This influx
of Na+ creates a capacitive local current flow through the adja
Current
R cent segments of membrane that alters the transmembrane volt
generator
age enough to reach threshold in these neighboring regions.
New voltage-gated Na+ channels open in the neighboring mem
brane allowing the process to repeat. This repetitive process re
sults in a continuous and complete depolarization of the entire
In
axon membrane as the action potential propagates away from
the stimulus site (Fig. 1-14). The sequential membrane activa
Figure '~'5. Capacitance and resistance. A, Simple circuit dia tion for each small region of axon takes a finite amount of time
gram depicting a capacitor connected to a current source. Positive as the depolarizing current: (1) first spreads to adjacent portions
charges build up on the capacitor connected to the wire labeled "in;' of membrane, (2) discharges the capacitor portion of the adja
producing a net positive charge on the plate.An equal number of posi cent membrane, (3) newly activated voltage-gated Na+ channels
tive charges are withdrawn (same as adding negative charges) from the undergo a conformational change, and (4) additional Na+ ions
capacitor labeled "out," creating a net negative charge on the plate. enter the axon. In unmyelinated axons, the cumulative time for
Although the two capacitor plates are separated by a nonconducting action potential generation by this process results in the slow
medium. current effectively flows across the capacitor because the conduction velocity of 10 -15 meters/second for fibers for
charges added to the "in" plate are removed from the "out" plate. axons with a diameter of 10 micrometers (/l).6
Charges flow until both plates equal the voltage of the current gener Each action potential generated by a particular membrane
ator. This process of charging the capacitor takes some time. S, The region is identical to the action potential from which it was gen
membrane also has passive channels through which current may flow erated; this phenomenon is called the all-or-none principle. 37
and effectively act as resistor. The cell membrane may be considered In unmyelinated axons, action potential propagation occurs as
to act as a capacitor and resistor in parallel. (From Koester J: Resting each small area of nerve activates its neighbor in a continuous
membrane potential and action potential. In Kandel ER. Schwartz JH fashion. These currents are active in the sense that they produce
(eds): Principles of Neural Science. 2nd ed. New York. Elsevier, 1985, pp a self-sustaining alteration in the transmembrane voltage as op
49-57, with permission.) posed to the passive spread over relatively small distances as in
Chapter I NERVEAND MUSCLE ANATOMY AND PHYSIOLOGY - 15
II
lil
h lL-_____________________________________
Figure ,-, 7. Saltatory conduction. A, In a myelinated nerve, the local circuit currents primarily flow into one node of Ranvier and extend
longitudina"y down the axon. exiting at the next node of Ranvier.There is a small amount of current lost in the internode region but not enough
to reduce the amount of current below necessary to depolarize the next node in line. B.A demonstration of the saltatory nature of conduction in
myelinated nerve. (From Koester J: Voltage-gated channels and the generation of the action potential. In Kandel ER, Schwartz JH (eds): Principles
of Neural Science. 2nd ed. New York. Elsevier. 1985. pp 75-86, with permission.)
even if ions could penetrate the axon membrane. Because of close together slow conduction by requiring unnecessary action
these electrical characteristics of the internodal axon membrane. potential generation at unneeded nodes. Investigators have
the inward Na+ current through a node of Ranvier spreads longi found that a nearly linear relationship between axonal diameter
tudinally toward the next node without the internodal membrane and internodal length is present. The apparent optimal inter
depolarizing. The nodal membrane contains a large number of nodal length is about 100 (75-175) times the axon's diame
Na+ ion channels compared to a similarly sized region of un ter. 52.57 An axon with a diameter of 10 ~m has an internode
myelinated membrane, which enhances sodium influx during length of approximately 1 mm. For a typical action potential ve
depolarization. The process is repeated until the end of the axon locity of 50 mls and duration of 0.5 milliseconds (ms), the
is reached (Fig. J-17A). action potential extends over 25 internodes (nerve conduction
Myelination significantly increases the impulse propagation velocity =distance/time; 50 mls = D/0.5 ms 25 mm). The in
velocity allowing speeds of up to 100 mls or more.22.37.66 The ternodes serving the entire action potential over this span are in
myelin eliminates the need to depolarize the internodal mem various stages of depolarization and repolarization (Fig. 1-18).
brane. The intracellular current quickly proceeds to the next Myelinated nerve consists of two components, myelin and
node where an action potential is generated (Fig. 1-17B). The axon, with an optimal ratio between them. For a given diameter
action potential essentially jumps from one node to the next. of axon, increases in myelin thickness create two opposing ef
This process is known as saltatory conduction (from Latin fects on conduction velocity. Increased thickness of myelin re
saltare. to jump or leap).6.2 2 In some mammalian nerves (includ duces internodal membrane capacitance, lessening local current
ing human), the nodal membrane does not appear to have volt leak, and increases propagation velocity. At the same time, axon
age-gated K+ channels. Repolarization is theorized to occur diameter is reduced, resulting in increased internal resistance
through a sodium back-leak or handled by the Na+-K+-ATP and decreased conduction velocity. Theoretical calculations pre
pump.63.66.67 Recall that depolarization and repolarization can 1ict that optimal conduction velocity occurs with a ratio of ap
occur through the alteration of sodium permeability according proximately 60% axon and 40% myelin. This agrees closely
to the Goldman-Hodgkin-Katz equation. Sodium channel inac with experimental measurements that have shown the ratio of
tivation decreases sodium permeability and allows the mem axon to myelin in various species is approximately 0.6. 61
brane to return to its resting state by the passive equilibration of Myelination effectively solves the problem of increasing con
sodium and potassium ions through the protein "leak" channels duction velocity without excessively increasing axon diameter.
of the membrane. The giant squid axon has a diameter of about 1000 ~m and con
ducts impulses at 25 mlS.6.29.37 A myelinated nerve with a diame
Optimizing the Myelinated Nerve ter of 20 ~m can have conduction velocities approaching 100
The distance between adjacent nodes of Ranvier influences mls. The result of myelination is a 50-fold reduction in diameter
conduction velocity. If the nodes are spaced too far apart, prop with a 4-fold increase in conduction velocity.6.22
agation may cease because the slowly declining intra-axonal Neural Classification. Two classification schemes have
current may be of insufficient magnitude to traverse an inter been developed to categorize the relationship between nerve
node and depolarize the next node in line. Node" that are too conduction velocity and fiber diameter. Erlanger and Gasser
Chapter I NERVE AND MUSCLE ANATOMY AND PHYSIOLOGY - 17
NEUROMUSCULAR TRANSMISSION
Skeletal muscles must first be activated by an electrical im
pulse prior to performing their essential function of moving our
joints. Large myelinated motor axons divide into a variable
number of fine terminal nerve branches, depending upon the
muscle, prior to synapsing with a muscle fiber. Large muscles
that perform gross movements, e.g., gastrocnemius, have a high
number of individual muscle fibers (greater than several hun
dred) innervated by each axon. Conversely, muscles requiring
fine motor control have a low terminal innervation ratio (ratio
of muscle fibers innervated by one axon) approaching one-to
one in the extraocular and vocal muscles. Each terminal branch
-60 attaches to a single muscle fiber at a specific region approximat
ing its mid-point referred to as the end-plate or neuromuscular
junction.48 Only about 2% of muscle fibers have more than one
Figure 1-18. Longitudinal expansion of the action potential. neuromuscular junction and these are found in especially long
The action potential's depolarization and repolarization is not an in muscles like the sartorius. 19
stantaneous event, but extends over a finite period of time during Neuromuscular Junction Anatomy. When a large myeli
which the impulse continues to propagate. As a result of this propaga nated motor axon approaches a muscle fiber, it divides into mul
tion, some portion of the nerve is depolarized while there are other tiple small nerve twigs that run along the muscle's surface for a
aspects of the nerve repolarizing over a somewhat longer time course. short distance before ending. The terminal portion of each axon
This has the effect of distributing the entire action potential over mul contains neurotubules and neurofilaments from the axon, multi
tiple internodes. The dashed lined represent the internodes over ple mitochondria for metabolic energy production, and large
which an action potential extends (about 25 internodes). (From Brown numbers of membrane-bound spheres 300-500 A in diameter
WF:The Physiological and Technical Basis of Electromyography. Boston, called synaptic vesicles, containing the neurotransmitter
Butterworth. 1984. pp 1-35. with permission.) acetylcholine (ACh).19 The region of the muscle fiber lying
under the nerve twig is called the motor end-plate (Fig. 1-19
and 1-20). Within this region of muscle are several muscle fiber
developed the first system. IS It considers both sensory and nudei, mitochondria, ribosomes, and pinocytotic vesicles. 48
motor fibers, and uses a combination of capital letters and lower Covering the entire end-plate are cytoplasmic extensions of the
case Greek letters. The second classification, by Lloyd and Schwann cell associated with the nerve twig innervating the
Hunt, uses Roman numerals I-IV and just considers sensory particular muscle fiber. The nerve's end portion, axon terminal,
fibers (Table 1-3).44 Nerve fibers belonging to groups A-8 and is not actually in contact with the muscle cell membrane but
I-III are myelinated, while categories C and IV designate un separated from it by a distance of about 50-75 nm. 19,48 This sep
myelinated nerve fibers. Larger fibers have greater conduction aration, the primary synaptic cleft, appears as an irregular
velocities than smaller fibers and myelinated axons conduct im region on electron microscopy and consists of multiple invagi
pulses faster than unmyelinated axons. nations into the muscle fiber creating secondary synaptic clefts
Figure 1-19. Neuromuscular junction.A neuromuscular junction involving skeletal muscle.A,A longitudinal section through the end-plate of
two terminal axons showing the presynaptic and postsynaptic regions overlying skeletal muscle. B, Overview of the same region in A. C, Close-up
of the neuromuscular junction detailing the synaptic vesicles, terminal axon lying in the synaptic trough and the subneural clefts. (From Fawcett
DW: Bloom and Fawcett:A Textbook of Histology. Philadelphia, w'B. Saunders. 1986, with permission.)
or subneural clefts 0.5-1.0 11m deep (Fig. 1-19).48 The postsy remarkable accomplishments. An action potential is propagated
naptic membrane corrugation serves to increase the end-plate along the axon into each of the multiple terminal axon twigs.
surface area. The ACh receptors are located on the summits of The action potential's conduction velocity slows considerably
the postsynaptic folds and are optimally positioned opposite the in the axon terminals to about 10-20 mls from the greater than
ACh release sites of the presynaptic membrane. 50 mls in the main axon. 35 The smaller diameter of the axon
twigs and loss of myelination near the neuromuscular junction
ELECTROCHEMICAL CONDUCTION causes conduction velocity to decrease. When the action poten
tial depolarizes the terminal axon, sodium conductance is in
The process of transferring electrical impulses from the in creased. In addition, Ca++ conductance also dramatically
nervating axon to its muscle fiber is one of the body's truly increases secondary to the presence and opening of Ca++ channels,
permitting calcium ions to enter the terminal portion of the axon. ACETYLCHOLINE RECYCLING
Calcium ion entry is critical to the process of neuromuscular
transmission; when CaH is removed from the extracellular The neurotransmitter ACh is confined within synaptic vesi
space, transmission ceases. Magnesium ions (Mg++) have been cles contained in the terminal axon. Confining acetylcholine in
shown to compete with Ca++ entry and can block the effects of vesicles likely (I) protects the molecules from breakdown by
Ca++. 13,14 Although the exact mechanism is unknown, Ca++ facili the small amount of an acetylcholinesterase (AchE) enzyme
tates fusion of the ACh-containing vesicles with the presynaptic present in the axon terminal, and (2) optimizes the necessary
membrane of the terminal axon. Once the vesicles have fused amount of transmitter released relative to the finite number of
with the nerve terminal membrane, ACh discharges into the vesicle binding sites. 22 Approximately 10,000 molecules of
synaptic cleft. An action potential releases between 100 and 200 acetylcholine are contained within a single synaptic vesicle and
vesicles at each axon terminal in amphibians compared to less are referred to as a quantum of acetylcholine. 41
than 100 vesicles in mammals. 37 ,48 The Ca++ persists in the axon At rest, there is spontaneous random release of synaptic vesi
terminal for approximately 200 ms keeping the axon terminal in cles or quanta. Spontaneous release is believed to reflect the
a "hyperexcitable state," enhancing the release of ACh if a presence of an intracellular resting level of Ca++ in the axon ter
second action potential depolarizes the axon within this time minal necessary for the normal physiologic functioning of the
frame. 15 mitochondria. 4 With release, ACh from one vesicle diffuses
The ACh quickly diffuses across the synaptic cleft (0.2-0.8 across the synaptic cleft heading for their receptors on the post
ms )36,54,56 to bind with ACh receptors. These receptors are large synaptic membrane of the end-plate (Fig. 1-21). Acetylcholin
transmembrane proteins that contain both a binding site for esterase enzyme molecules, in addition to their location in the
ACh and an ion channel. The ACh receptors are located primar axon terminal, are also evenly distributed throughout the pri
ily but not exclusively on the summits of the secondary synap mary and secondary synaptic clefts, weakly attached to the sar
tic clefts at an approximate density of 20,000 to 25,000 colemma. 48 It is estimated that there are between 3,000 and
receptors per 11m2 of membrane,32.54 These receptors are li 6,000 AChE molecules per 11m2 in the postsynaptic mammalian
gand-activated rather than voltage-gated. The surface portion membrane.? Hydrolysis of the acetylcholine molecules into
of the protein acts as a receptor for the ACh molecule. When choline and acetate begins soon after they are released into the
the ACh ligand fuses with its receptor, a conformational change cleft region. The surviving acetylcholine is free to bind to its re
occurs in the channel portion of the receptor that opens the ion ceptor, resulting in a small amount of postsynaptic membrane
gate for about 1 ms,22 depolarization (Fig. 1-21). The magnitude of the intracellularly
The channel opening is large enough to allow transmembrane recorded depolarization resulting from the remaining acetyl
flow of Na+, K+, and Ca++ cations. When open, the channel choline molecules is about 1 mV; it is referred to as a miniature
allows nonspecific cation influx; however, anions are not per end-plate potential (MEPP)18 and occurs approximately once
mitted to pass as the inner wall of the channel is negatively
charged and repels anions such as Cl-, Similar to the nerve fiber
membranes, the major ion influx causing depolarization is Na+,
Although the K+ ion can easily fit through the open channel, the
resting membrane potential of - 90 m V to - 80 m V for muscle
is close to the equilibrium potential of K+, which restricts large
potassium effluxes. Calcium ions are present outside of the
muscle and do enter the muscle to some extent, but the concen
tration is 50 times less than that of Na+.
The Na+ normally entering the end-plate region is sufficient
to depolarize the adjacent muscle fiber membrane. The quantity
of Na+ that normally enters through the ion channels reverses
the transmembrane potential of the end-plate region by as much
as 75 mY. This greatly exceeds the threshold voltage of approx
imately 15 mV needed to initiate the positive feedback loop of
sodium activation. The voltage difference between the threshold
level and the final magnitude of the end-plate potential is re
ferred to as the neuromuscular junction's safety factor. This
large safety factor ensures that even under normal physiologic
repetitive nerve action potential generation during which the
amount of ACh released from the axon terminal decreases,
enough ACh continues to be emitted to exceed threshold.
Localized non-propagating reversals (depolarization) of the
muscle end-plate'S transmembrane potential by any amount is
referred to as the end-plate potential (EPP). The spread of this
potential is purely by electrotonic means over the end-plate Figure 1-21. ACh release and synthesis. Sequential steps in
I '
region. If enough ACh is released to reach or exceed threshold, volved in the ACh cycle in the electrochemical transmission in muscle
the EPP is quickly overtaken by the generation of an action po activation. ACh, acetylcholine, AChE, acetylcholine esterase, AChR,
tential. This action potential then results in depolarization of the acetylcholine receptor. CoA, coenzyme A, Ch. choline. See text for ex
muscle membrane surrounding the end-plate and an all-or-noth planation of process and Figure 1-20. (From McComas AJ:
ing propagating impulse is initiated in the muscle fiber (see Neuromuscular Function and Disorders. Boston, Butterworth. 1977,
Muscle Tissue). with permission.)
20 - PART I FUNDAMENTAL PRINCIPLES
MUSCLE TISSUE
50A The primary function of muscle tissue is to create forces that
allow for efficient movement. This section covers the mecha
Figure 1-23. Model ofthe nicotinic acetylcholine receptor. nisms by which muscular tissue contracts and generates tension.
The model includes the quaternary structure (clockwise arranged sub Basic muscle histology and architecture, the fundamental elec
units a, 0'. p, and IX; the 'Y subunit in front is removed). the helix TM2 trical properties of muscle membranes, the neuromuscular
forming the channel wall, the negative charges arranged in three rings, synapse, and excitation/contraction coupling are reviewed.
which determine channel conductivity and selectivity, and the binding Since the basic concepts of nerve and muscle membrane physi
sites for the a-neurotoxins at the subunit interfaces (Tx). (From ology are relatively similar, only the specific details of muscle
Fawcett DW: Bloom and Fawcett: A Textbook of Histology. electrophysiology are noted. Additional details of muscle elec
Phiiadelphia,w'B. Saunders, 1986, with permission.) trophysiology can be found in standard physiology texts. 19•22,23
Chapter I NERVE AND MUSCLE ANATOMY AND PHYSIOLOGY - 11
Myofibrils
Figure 1-24. Muscle tissue. Section through skeletal muscle demonstrating the various subcomponents of muscle tissue. In mammalian muscle
the T tubule would align with the All bands as opposed to the Z line as shown above. The mammalian skeletal muscle, therefore. would have two T
tubules per sarcomere (Z line to Z line). (From Fawcett OW: Bloom and Fawcett: A Textbook of Histology. Philadelphia. W.B. Saunders, 1986, with
permission.)
22 - PART I FUNDAMENTAL PRINCIPLES
SKELETAL MUSCLE
Muscle Fasciculus
J
,
esesses
, s , ,J l aes ••• s
p , s •
l
l
... 1/ t .......... \J M
e
F G H I
• •• .:-:.:.
~-. /
I "''''...
"' ...,
...: ...
• • ••
•••••••• -:-:.:.:-
.:-:.:-
.' 'e::o N
• • •••• Ll9'"
U:~1Il
••• Met'omyOlill
Figure 1-25. Skeletal muscle subcomponents. Increasing magnification of the skeletal muscle's subcomponents. (From Fawcett DW: Bloom
and Fawcett: A Textbook of Histology. Philadelphia, W.B. Saunders, 1986, with permission.)
called T (transverse) tubules and allow the extracellular space out from the tail through an arm segment. One myosin filament
to extend all the way across the muscle fiber from one side to contains about 200 of these single-tailltwo-head molecules,
the other. 19•22 The T tubules contain extracellular fluid and form with the heads projecting outward from the central conglomera
an intricate channel system throughout the muscle's interior tion of tails forming the main filament. The head and its project
(Fig. 1-24). The sarcolemma is covered externally by a 50-nm ing part are referred to as a cross-bridge; it has two flexible
thick basement membrane, which is composed of polysaccha hinges, one at the head/arm and the other at the annIfilament in
rides and protein. 48 The basement membrane provides support terface (Fig. 1-2ti). Each myosin head acts as an ATPase to
for the muscle fiber and may act as a catchment area to prevent cleave a molecule ofATP.22 The energy liberated by this process
effluxing ions from diffusing too far from the sarcolemma. Just is used to maintain the cross-bridge in the extended or "cocked"
on the interior of the sarcolemma and suspended from it are the position. The entire myosin filament is twisted about a central
muscle cell's nuclei. Multiple nuclei are dispersed along the axis allowing the cross-bridges to extend longitudinally and cir
length of the muscle fiber. cumferentially 360 0
•
Contained within the muscle cell are myofibrils, the struc The actin filament is composed of three subcomponents:
tures responsible for muscle contraction (Fig. 1-25). Myofibrils actin, tropomyosin, and troponin (Fig. 1-26). Two helical
consist of two large polymerized protein molecules forming the strands of F-actin, composed of pol ymerized G-actin molecules,
myosin and actin filaments. A myosin molecule consists of a form the primary structure of the actin filament. Each G-actin
single tail attached to two head portions, each of wl.ich extends molecule contains one molecule of ADP. Wound loosely within
Chapter I NERVE AND MUSCLE ANATOMY AND PHYSIOLOGY - 2l
Heavy
_meromyoSin __
IHMM
HMMS-2 S-1
160.0001 «20,000)
light meromyosin
Cv.lO.OOIll
A
Myosin molecule
Myosin filament
I
MbA
Actin filament
D E
Figure 1-26. Myofilament structure. Proposed composition of the myofilaments involved in muscle contraction and the molecular basis of
contraction. A, Subcomponents of the myosin molecule. B, Foreshortened arrangement of the myosin filament. C,The actin filament's double heli
cal composition with the troponin complex attached. D-E, Hypothesized mechanism of Ca++ binding to the troponin/tropomyosin complex re
sulting in a conformational change exposing actin's active site. The myosin head attaches to the actin and moves this filament along. (From Fawcett
DW: Bloom and Fawcett A Textbook of Histology. Philadelphia. WB. Saunders, 1986, with permission.)
the helical structure of the F-actin are two strands of a tropo The larger myosin and smaller actin filaments interdigitate,
myosin molecule. The tropomyosin molecules are believed to giving the myofibrils their characteristic alternate light and dark
overlie "active sites" on the actin molecules. It is these "active bands (Fig. 1-25). The light bands consist only of actin filaments
sites" that are the linkage sites for the myosin cross bridges. and are "isotropic" to polarized light, hence they are called I
Troponin, the third subcomponent of the actin filament, is at bands. One end of the actin filaments is firmly anchored to the Z
tached two thirds down the tropomyosin molecule and consists disc and the other end projects out between myosin filaments.
of three globular proteins: troponin I, T, and C (Fig. 1-26). These Z discs extend from myofibril to myofibril across the di
Troponin I binds strongly to actin, troponin T is attached to ameter of a muscle fiber. The region of muscle or myofibril be
tropomyosin, while troponin C has a large affinity for Ca++. The tween two Z discs is called a sarcomere (Fig. 1-25). The light or
troponin complex attaches the tropomyosin molecules to the I band is flanked by two dark bands composed of overlapping
actin molecules, thereby forming the complete actin filament. actin and myosin filaments that are "anisotropic" to polarized
24 - PART I FUNDAMENTAL PRINCIPLES
light, hence A bands. The interaction between the myosin cross of the neuromuscular junction area. An induced action potential
bridges and actin filaments causes the muscle fiber to shorten or then propagates along the sarcolemma. Voltage-gated Na+ chan
contract because the above-noted filaments slide past each other. nels open, further altering the transmembrane potential and
Down the middle of an A band lies the H zone, which is merely opening additional voltage-sensitive Na+ channels. The in
a lighter-colored region where actin filaments do not abut each wardly directed Na+ current then spreads longitudinally down
other in a muscle longer than its resting length (Fig. 1-25).22 the muscle fiber and completes a local circuit current by ~is
Sarcoplasm is the intracellular fluid surrounding the myofib charging the capacitance of the membrane. In unmyelinated
ril. This fluid contains the aqueous ions of potassium, magne nerve, discharging the regional membrane capacitance takes
sium, phosphate, sodium, and multiple enzymes. 48 Large time, contributing to the slow conduction velocities of 25-30
numbers of mitochondria are suspended in the sarcoplasm and m/s. Muscle fibers conduct action potentials similarly to un
lie in and about the myofibrils (Fig. 1-24). Mitochondria sug myelinated nerves; they do not possess myelin and, therefore,
gest that the muscle cell requires substantial energy for the con must rely upon each segment of membrane depolarizing the ad
traction process. The myofibrils are also surrounded by an jacent regions. Of interest is the observation that muscle fibers
intricate series of channels called the sarcoplasmic reticulum. of comparable size to unmyelinated nerve have slower action
Longitudinal sarcoplasmic reticulum channels end in a rela potential conduction velocities. 22 The reason for this is the in
tively large common terminal cisternae at either end of the sar creased surface area of muscle membrane due to the T tubule
comere (Fig. 1-24). Within the muscle fiber, T tubules are system. With more membrane to depolarize, a larger capacitor
closely associated with terminal cisternae at each demarcation must be discharged. Discharging a larger capacitor, or bringing
between the A and I bands. Two terminal cisternae are in close more membrane to threshold, takes more time. Slowed muscle
association with one T tubule to form a so-called triad. fiber depolarization results in an action potential duration about
Although these three structures are in very close association, 5 times greater than nerve, and conduction velocities on the
there are no known channels connecting them. The triad is criti order of 3-5 rnIs for mammalian muscle. 22
cally positioned next to where the muscle fiber's mechanism The unique properties of T tubules result in a number of note
produces the necessary forces for contraction. The T tubule is worthy effects. Because of the rather small confines of the T
believed to conduct an action potential into the depths of the tubule system, effluxing K+ accumulates in the region just out
muscle and into the terminal cisternae. side of the sarcolemma during repolarization. The increased
concentration of K+ just outside the membrane during the latter
ELECTRICAL ACTIVITY portion of repolarization tends to depolarize the cell again, i.e.,
the localized extracellular accumulation of K+ alters the concen
Resting Membrane Potential tration gradient across this portion of the membrane, altering
Inserting a microelectrode into a mammalian muscle cell re the transmembrane potential. Recall from the Goldman
veals a resting membrane potential of approximately 80 to 90 Hodgkin-Katz equation that increasing the extracellular concen
m V negative compared to the extracellular space. By measuring tration of K+ tends to make the transmembrane voltage more
the concentrations of various ions inside and outside of the positive, i.e., a bias toward depolarization. Accumulated K+ can
muscle cell (Table 1-2) and using the Goldman-Hodgkin-Katz diffuse back into the cell following repolarization and again de
equation, it is possible to calculate the resting membrane poten polarize this aspect of the membrane. This effect can actually be
tial and arrive at - 90 m V. The basis of the resting membrane observed as an afterdepolarization on the falling phase of a
potential in muscle is very similar to that for nerve. muscle's action potential. 48 This afterdepolarization can last for
The sarcolemma is a semipermeable membrane that allows several hundred milliseconds and may summate with repetitive
chloride and potassium ions to pass but restricts the movement activity. Fibers may become self-activating and continue to fire
of extracellular sodium cations and intracellular anions. in a self-sustaining manner. This may be the explanation of
Remember that the sarcolemma also has a rather large portion some myotonic conditions in which chloride conductance is re
extending into the muscle fiber itself. Investigations have duced (see Chapter 27). Nature has obviated repetitive muscle
demonstrated that the T tubules possess permeability to K+ ap firing from T tubule K+ accumulation by providing the sar
proximately twice that for the surface portion of the sar colemma with a 10 times greater Cl- than K+ conductance. The
colemma. 23 .47 There is, however, a rather slow effect on the increased Cl- conductance allows for a relatively large influx of
membrane potential when the extracellular potassium concen negative chloride ions to assist in repolarization. An inward neg
tration is reduced. The narrow T tubules restrict the rapid diffu ative current essentially means that only a small amount of K+
sion of K+ through the ion channels and into the extracellular ions need efflux from the cell to repolarize the transmembrane
space. The restriction is a result of a build-up of positive charges potential back to the resting level following depolarization. The
that hinder continued efflux. Just as for nerve, the resting mem increased Cl- conductance tends to reduce the total amount of
brane potential for muscle approaches the equilibrium potential K+ accumulation and minimize any chance of repetitive activity
for potassium, but is a bit off when the extracellular concentra due to potassium ion build-up.
tion of potassium is reduced. The implication is that a second
Excitation-Contraction Coupling
ion is responsible for just a portion of the resting membrane po
tential. As for nerve, the second ion turns out to be sodium. Excitation
Voltage clamp experiments and ion channel poisons have docu An action potential is initially produced at the end-plate
mented voltage-gated sodium and potassium gates in the sar region, which then propagates along the muscle membrane and
colemma similar to those in unmyelinated nerve. 21 extends into the T tubule system. Once in the T tubule, the
action potential causes calcium release from the sarcoplasmic
Action Potential Propagation reticulum's terminal cisternae (Fig. 1_27).22,23 Although the
As stated previously, an action potential traveling down a exact mechanism of calcium release is unclear, junctional feet
nerve can enter the end-plate region and result in a depolarization projecting from the cisternae to the T tubules presumably assists
Chapter I NERVE AND MUSCLE ANATOMY AND PHYSIOLOGY - 25
,,-- ....
I "
Actin filaments
in calcium release. 48 The sarcoplasmic reticulum contains large in sarcomere shortening: excitation/contraction coupling. In the
quantities of Ca++ that are released to bathe the myofibrils. The absence of ATP, the actin and myosin molecules remain in the
muscle continues to contract as long as Ca++ is present. The Ca++ joined position resulting in rigor mortis.
ions surround the myofibrils in sufficient quantities to facilitate
contraction for approximately 1/30 second. At the end of this
period, a Ca++ pump rapidly sequesters the calcium ions back CONCLUSION
into the sarcoplasmic reticulum reducing the concentration of
Ca++ below that necessary for continued contraction (Fig. 1-27). All practitioners wishing to practice electrodiagnostic medi
cine must understand the fundamentals of nerve and muscle
Contraction physiology. During the course of an electrodiagnostic medicine
Once the calcium ions have been released from the sarcoplas examination, the practitioner investigates either directly or indi
mic reticulum, up to four Ca++ ions are proposed to bind rectly nerve and muscle resting membrane potentials and the
strongly to troponin c. 48 Calcium ion binding apparently results generation of action potentials. The manner in which nerve and
in a conformational change of the troponin complex that alters muscle respond to the investigative procedures of the practitioner
the relationship of tropomyosin to actin (Fig. 1-26). In the in both health and disease can only be fully appreciated through
process of changing position, the tropomyosin is thought to an understanding of nerve and muscle physiology. The electrodi
expose "active" sites on the G-actin molecule. These active sites agnostic medicine principles discussed in the remainder of this
on the actin molecule are believed to be adenosine diphosphate text are based on the concepts delineated in this chapter.
(ADP) molecules. Although the exact mechanism of contraction
is unknown, the "walk-along" hypothesis proposes that as soon
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26 - PART I FUNDAMENTAL PRINCIPLES
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Chapter 2
CHAPTER OUTLINE
Nerves and muscles are bioelectric source generators. They VOLUME CONDUCTION THEORY
consist of multiple subcomponent fibers generating transmem
brane action potentials through which ionic currents spread VOLUME CONDUCTORS AND ELECTROPHYSIOLOGIC
into the extracellular tissue. An extracellular recording from RECORDING PRINCIPLES
these currents is typically obtained by an electrode placed on
the skin surface, or a needle electrode inserted through the Volume conduction theory describes the three-dimensional
skin and placed in close proximity to the nerve or muscle spread of electrical current (current:;; charge movement) in any
fibers. The ensuing waveform depends on the summation of conducting medium. 14•19,33 It is governed by the laws of electro
individual electric current fields generated by the transmem statics. Lorente de N6 made an extensive study of this subject in
brane action potentials of the excited neural or muscular tis 1947. 82 Due to the various physical shapes and the heteroge
sues. These waveforms have unique shapes and sizes in both neous and anisotropic properties of the human body as a volume
normal and pathologic conditions. Any clinician practicing conductor, the solutions to this problem in terms of physics and
electrodiagnostic medicine should possess a thorough under intuition are not trivial. The fundamental principles of volume
standing of action potential generation and why these poten conductor theory may be understood by considering a simple
tials appear as they do to properly formulate a diagnosis. A example of a beaker containing a dissolved table salt solution
flawed understanding of waveform morphology may result in (NaCl). Sodium chloride dissolves and forms individual posi
an erroneous medical impression. tive sodium ions (Na+) and negative chloride ions (CI-). These
The subtleties of near-field and far-field waveforms as they ions are electrically charged and mobile in solution, and hence
relate to both innervated and denervated tissues are explored in capable of mediating an electric current. If we now connect two
more detail in the appendix to this chapter. wires to the positive and negative terminals of a battery and
27
28 - PART I FUNDAMENTAL PRINCIPLES
./' Current source mobile in the solution, they form current pathways in three di
mensions between the two battery poles. In Figure 2-2 current
lines are shown schematically with an increasing and decreas
ing amount of space separating them. The amount of separation
from one current line to the next depicts the current density
which is greater near the battery poles than further away. 14. 19:82
We can use the beaker example to explore a number of con
cepts important to the understanding of volume conduction. The
two battery poles essentially act as a dipole (+,-) where current
Electrode flows from the positive to the negative pole. 38 Let us focus on
just the dipole with its accompanying current (Fig. 2-2).
Extending out from the dipole at right angles to the current lines
is a set of lines referred to as isopotentiallines. 38 One isopoten
Line of highest
current density
tialline represents a constant potential or voltage magnitude
along its entire length. The potential's magnitude associated
with a specific line decreases as one proceeds toward the zero
Current paths isopotentialline midway between the two poles (Fig. 2-2).
The spatial gradient is defined as the rate of change of a p0
tential in a volume conductor as a function of distance.38 The
spatial gradient is high when differences in potential are large
Figure 2-1. Volume Conductor. A current source is immersed in between adjacent points. The concept of a spatial gradient can be
a beaker containing an electrolytic solution that serves as a good used to define different aspects of the potential distribution asso
volume conductor. Note that the current lines fan out into the volume ciated with a current source in a volume conductor. The designa
conductor as well as align directly between the two battery poles. tion near field defines a region of the volume conductor
(From De Lisa JA, Brozovich FV:Volume conduction in electromyogra surrounding a current source where the spatial gradient from the
phy: Experimental and theoretical review. Electromyogr elin Neuro current source is relatively high. 38,lol Potentials recorded in this
physiol 1983;23:651-673, with permission.) portion of the volume conductor are called near-field potentials.
Signals detected at some distance from the current source where
place the bared tips in the beaker containing the salt solution, the potential gradient is low are known as far-field potentials. 38
the positive ions (cations) and negative ions (anions) are at A number of electrodes can be placed at various locations in
tracted to the negative pole (cathode) and positive pole (anode) the volume conductor around a dipole current source (Fig. 2-2).
of the battery, respectively (Fig. 2-1).19 Because the ions are It can be inferred from the above that if two electrodes are lo
cated on two different isopotential lines, a potential difference
will be detected. No potential difference will be detected be
tween two electrodes on the same isopotential line, no matter
how far apart they are or how large the voltage magnitudes. In
E Figure 2-2, none of the electrodes are on exactly the same
\ isopotential line. Therefore, a potential difference exists be
tween any two electrode pairs. This observation suggests that a
potential difference, albeit small, in some electrode pairings
(montages), will be measured between any electrode combina
tion shown. The potential difference between each electrode
pair, however, is not the same, and different amplitudes can be
anticipated with each different electrode montage.
Consider two electrodes positioned close together on differ
ent isopotentiallines, for example C and D in Figure 2-2, but lo
cated relatively far from the dipole current source. These two
electrodes constitute a bipolar recording montage, i.e., two
electrodes in close proximity to each other with respect to an
electrical generator.58.59.71,72 If the potential difference between
the two electrodes is negligible, as is the case far from the elec
trical generator, the detected waveform will also be of small
+ size. In other words, if the spatial gradient of the voltage distrib
ution is low, there is a very small difference in potential detected
Figure 2-2. Dipole current/voltage distribution. Distribution of by two electrodes relatively close together.
current lines about a dipole generator in a good volume conductor. A bipolar electrode montage located somewhat closer to the
The current lines extend between the positive and negative poles, dipole generator can detect a larger potential difference between
while the isopotentiallines are perpendicular to the current lines. Five the two electrodes (Fig. 2-2, electrodes A and B). In this in
recording electrodes are positioned at various locations within the stance, the potential difference is relatively large because the
volume conductor. Electrodes A and B are in a region of a high current spatial potential gradient is high near the impulse generator. As
spatial gradient but C, D, and E are in a relatively lower spatial gradi a result, the voltage difference between the two electrodes (A
ent. (From Dumitru D, Jewett DL: Far-field potentials. Muscle Nerve minus B) is relatively large and yields a larger potential than C
1993;16:237-254, with permission.) minus D. Bipolar recordings, therefore, are useful in documenting
Chapter 2 ELECTRICAL SOURCES AND VOLUME CONDUCTION - 29
the presence or absence of electrical activity in the localized with reversed polarity (swapping electrodes at the amplifier).
region of the electrodes when they are in the near-field, but on So, the distance between the electrodes and the exact positions
different isopotential lines. This fact can be taken advantage of have a pronounced influence on the measured signals.
when attempting to minimize stimulus artifact by rotating the Furthermore, the physical dimensions of the electrodes are im
stimulus anode about the cathode, thereby attempting to alter portant. It can be generally assumed that the electrode records
the stimulator's isopotential lines so that both recording elec the average of the potential field under its surface. The mea
trodes are located on the same isopotentialline of the stimulus sured signal can be influenced considerably when large-size
artifact (see Chapter 3). electrodes are in a region with high spatial gradients.
If one of the electrodes close to the generator source (A or B) In electrodiagnostic medicine, an electrical signal is usually
is used with an electrode further away (C, D, or E), then A or B displayed on the instrument's screen. If the net voltage differ
are said to be "referenced to" C, D, or E. This type of recording ence between the two recording electrodes is negative, the in
is referred to as a referential recording montage or a monopo strument's trace moves upward (negative up) or downward
lar recording montage. 70•72 The electrode A or B, positioned in (positive up). The actual direction of travel is determined by the
a high spatial gradient region, is "referenced" to an electrode lo manner in which the investigator connects the electrodes to the
cated in an area with a low spatial gradient. A larger potential instrument and is merely a matter of convention. Practitioners
difference exists between A or B connected to C, D, or E com of electrodiagnostic medicine use the convention of "negative
pared to a bipolar recording between either A and B, or C and up" and "positive down." Unless otherwise stated, this conven
D. This is because a referential electrode montage usually com tion is used throughout this book. The just discussed volume
pares a region of high to one of low voltage, i.e., after having conduction as explained by the beaker salt solution can also be
passed many isopotential lines, the result is a large measured viewed as a filtering process. The advantage of this approach is
potential difference. So, referential montages may record poten that filtering is usually rather familiar to the electrodiagnostic
tials with larger amplitudes than bipolar montages if one of the physician. The conducting medium acts as a spatial low-pass
electrodes is positioned in the same location for both types of (high-frequency) filter resulting in smoothing of the signals.
recordings, e.g., montage A-E (e.g., a monopoiar needle elec This implies that the further away the recording electrodes are
trode) compared to montage A-B (e.g., a concentric needle from the source, the lower the amplitudes are with a more pro
electrode). 8 nounced effect on the high-frequency parts of the original
Electrode terminology can be rather confusing. One electrode signal. The electrode size and interelectrode positions also act
of a pair is typically referred to as an "active electrode" and the as spatial filters. The spatial filter characteristics turn into an
other as a "reference electrode." The term "active" is used by equivalent temporal filtering as soon as, and merely when, one
convention when this electrode is located in the neighborhood deals with the travelling aspect of an action potential. It is im
of the electrical generator where the spatial gradient is high. The portant to realize, however, that although increasing the distance
reference electrode is usually placed where the spatial gradient between source and recording electrode deeply influences the
is lower than that for the active electrode. The active electrode is shape of the waveform, time relations are not influenced. Thus,
plugged into the (+) amplifier port that magnifies the signal un measuring a travelling nerve action potential from nearby with
changed, while the reference electrode is connected to the (-) needle electrodes or at large distances with a surface electrode
amplifier port that magnifies and inverts the signal (see Chapter (at a level perpendicular to the direction of the action potential)
3).30 The two magnified signals are summated (active minus ref gives different shapes and amplitUdes, but nearly identical la
erence) and displayed or used for further analysis. This proce tencies for the different waveform subcomponents.
dure is called differential amplification (see Chapter 3). All
recording montages can be said to consist of an active and refer Action Potential Source Generation
ence electrode, although in bipolar recordings the active elec All living cells possess the unique characteristic of a resting
trode is compared to a reference electrode, which is also membrane potential with the intracellular region negative (ap
relatively close to the impulse generator. proximately - 90 mY) compared to the extracellular space. 2•67
One may also consider a referential far-field montage (Fig. 2 The cell membrane is responsible for developing and sustaining
2). Electrode C or D may be connected to electrode E to com this transmembrane voltage difference because of its semiperme
prise a far-field referential montage. Since both electrodes able nature. Most cells contain a high intracellular concentration
(either Cor D connected to E) are in a region of low spatial gra of positive potassium ions (K+) and negatively charged proteins.
dient, it is hard to define which of the two is the "reference" In the resting state, the semipermeable membrane allows intra
electrode. Finally, the distinction between the "active" and "ref cellular potassium ions to exit the cell "down" a high intracellu
erence" electrodes also becomes blurred in bipolar montages lo lar to low extracellular concentration gradient. 2 •67 This process
cated in a region where the spatial gradient does not change continues until it is balanced by an inward electrical attraction
significantly (Fig. 2-2, C and D). Therefore, the distinction is from the intracellular protein anions that cannot exit the cell. A
inadequate in many occasions. The terms E-l (electrode 1) and net negative charge results when a dynamic equilibrium is estab
E-2 (electrode 2), or 01 (grid 1) and 02 (grid 2) may be better lished between the forces driving K+ out of the cell (concentra
descriptors for recording electrodes where the observed wave tion gradient) and an inwardly directed force (electrical gradient)
form is a result of E-I minus E-2, formerly "active" minus "ref from the anions attracting the K+ into the cell.
erence." The terminology E-l and E-2 is preferred over 01 and The resting membrane potential is influenced to a small
02 since the latter terms refer to vacuum tube amplifiers, which degree by the relatively impermeable positive sodium ions
are no longer used as electrodiagnostic equipment. (Na+). There are two strong forces driving sodium into the cell.
As is obvious from the above explanation, the same active The first is the concentration gradient, high extracellular and
bioelectric source can be recorded as a flat line (both electrodes low intracellular Na+ concentration, and the second is the nega
on an isopotential line), with high amplitude (one electrode in a tive intracellular potential, Le., electrical gradient. Although rel
high spatial gradient and the other in a low spatial gradient), or atively impermeable, small quantities of Na+ do leak into the
30 - PART I FUNDAMENTAL PRINCIPLES
cell tending to alter the resting membrane potential. A steady back to - 90 mV (Fig. 2-3A).48.89 The cell, therefore, produces a
state situation with a constant resting membrane potential is positive monophasic intracellular action potential beginning at
maintained by actively pumping K+ into the cell and pumping - 90 mV, increasing to about + 40 mV, and then returns to - 90
out Na+ from the cell (the sodium-potassium ATPase pump).2.62 mV.99 The action potential's appearance as characterized by its
This steady-state voltage approaches the equilibrium potential amplitude, duration, rapid rise, and relatively slow baseline
of K+ with a minor modification due to the influence of Na+ (see return is directly dependent upon the temporal aspects of Na+
Chapter 1). and K+ activation/inactivations7 (Fig. 2-3A). For a more detailed
Nerve and muscle cel1s are known as excitable cells because description of the resting membrane potential and the action po
transient action potentials can be induced via an active process tential generation in both myelinated and unmyelinated nerve,
that is based on the behavior of the voltage-gated ion channels see Chapter 1.
in the membrane. If the resting membrane potential is depolar
ized to dJe threshold level (approximately - 65 mY), following Local Circuit Currents
appropriate chemical, mechanical, or electrical stimuli, such an The impermeable protein anions located within excitable tis
action potential is produced.2.19.67 The action potential arises sues attract extracellular positive ions, primarily Na+, because
from an alteration in voltage-gated channels control1ing the per of its abundance, and cause them to align along the extracellular
meability of Na+ and K+. At the threshold voltage, the voltage surface of the cell's membrane. In effect, there is a series of neg
gated sodium channels open allowing Na+ to enter and further ative and positive charges aligned along the cell's length sepa
depolarize the cell, thereby inducing more sodium gates to open rated by the membrane (Fig. 2-3B). During an action potential,
in a positive feedback manner driving the intracellular voltage inwardly flowing positive Na+ ions proceed longitudinally
toward + 55 mV (sodium equilibrium potential; Fig. 2-3A). This along the interior of the axon. These additional intracellular
process of depolarization lasts about 0.1 ms in mammalian positive charges balance a portion of the intracellular anions,
nerves and travels along the nerve fiber. 89•90•113 The cell's resting which attracted the extracellular Na+. The transmembrane elec
membrane potential depolarizes from - 90 m V to approxi trical attraction for Na+ is subsequently reduced allowing those
mately + 40 mV.66 A delayed increase in K+ permeability lasting extracellular Na+ ions increased freedom to move away from the
about 0.4 ms in mammalian unmyelinated nerve in conjunction immediate vicinity. The increased permeability of the depolar
with inactivation of the sodium gates restores the membrane ized membrane permits those now even more mobile Na+ ions
-Monophasic Potential
o
o--------~------~~----------
+
Figure .2-3. Action potential generation in an unmyeli
nated nerve.A,Alterations of Na+ conductance above thresh
old results in depolarization. while increased K+ conductance
c helps establish the resting membrane potential. The net result of
these two processes is a monophasic positive intracellular
action potential. B, The transmembrane dipolar arrangement of
intracellular and extracellular ions is depicted. C, Local circuit
currents distributed within a thin film of saline surrounded by a
poor volume conductor (mineral oil). Note how the local cir
cuit currents are confined to the saline and "hug" the membrane
surface. Four sequential electrode locations sample the extra
cellular potential within the saline film. In a good volume con
ductor. such as the body. the local circuit current expands away
B
from the nerve surface. D.A monophasic extracellular wave
PotassiumEffm form resulting from the local circuits that corresponds to the
intracellular action potential. (From Dumitru D:Volume conduc
• • • ++ . . . . . . . . ++ + ........... .
• No K tion: Theory and application. In Dumitru D (ed): Clinical
I
•
I
Electrophysiology. Philadelphia, Hanley & Belfus. 1989. pp
A + : 665-681, with permission.)
E
O~--------~4-~~-------------
I
.
I
,Ih \ ,
: 1 \ ...... .J...
1------., :.~ \ : '-, " J~ \ I .,
~. I
'J
....... _
.,
....... ~gl(
............
•
to enter the cell intensified through the already open Na+ chan current, results in a potential rise (positive potential). So, a
nels. This sequence of extracellular Na+ entering the cell and movement against current flow (opposite the local circuit cur
neutralizing the transmembrane attraction toward extracellular rent's direction) produces a positive trace deflection on the in
Na+ ions thereby allowing them to move away from the mem strument, while travel in the direction of current flow (in the
brane's surface and also to enter the cell is referred to as a local same direction as the local circuit current) results in a negative
circuit (Fig. 2-3C; also see Chapter 1).2.67 This local circuit screen trace deflection.
leads to relatively more positive charges intracellulariy and The concept of moving with or against the direction of the
fewer positive charges extracellularly adjacent to the depolar current may be considered from two perspectives. First, let us
ized portion of membrane. That portion of membrane where ex imagine that an action potential is propagating along a nerve or
tracellular Na+ ions are no longer held to the surface of the muscle toward a non-moving electrode. In this instance, the
membrane, but are free to enter the cell through the local circuit local circuit currents associated with the action potential will
current constitutes the current source. The region of membrane pass by the electrode. The direction of current flow with respect
through which the sodium ions enter the cell (open voltage-de to the electrode, in or out of the cell, will determine the direc
pendent gates) is called a current sink. 2.67 The source current tion of the upward or downward deflection. Second, we may
tends to depolarize the cell's adjacent membranous regions sur consider an action potential with its local circuit currents direc
rounding the current sink by reducing the local surface positive tion of travel suspended or "frozen" for an instant in time. The
charge and reversing the intracellular to extracellular voltage re electrode can then be moved past the local circuit currents to de
lationship. The self-sustaining nature of these processes results scribe what it measures at that moment for which the action p0
in action potential propagation. tential is suspended. The results from both scenarios are
The current sink from a propagating action potential permits equivalent with respect to the action potential's configuration.
positive sodium ions to extend not only into that portion of Whether the electrode moves by a non-moving action potential,
nerve or muscle previously depolarized, but also into the region or the action potential propagates past a non-moving electrode,
of the tissue about to be depolarized i.e., a bidirectional intra the net waveform result is the same. For discussion purposes, it
cellular current flow. Extracellularly, the sodium ions are is often easier to consider the local circuit currents of an action
moving into the sink from portions of the volume conductor potential at one moment in time and move an electrode through
both preceding and following the traveling action potential. In the local circuit currents. The assumption is that the local circuit
effect, there are two intra-/extracellular local circuit currents currents do not change with action potential propagation along
associated with a propagating action potential (Fig. 2-3C).2.67 the course of the excitable tissue examined.
This observation leads to the common source description of a
travelling action potential consisting of a "source-sink-source"
arrangement. 94 LOCAL CIRCUIT CURRENTS INYOLUME
CONDUCTORS
Circuit Model of Waveform Morphology
Consider a simple battery circuit with one resistor (Fig. 2 Waveform Morphology in a Restricted-Volume
4).39 The direction of the current in the circuit is from the posi Conductor
tive to the negative battery pole across the resistor. The current An excitable cell surrounded by a thin film of saline can be
across the resistor results in a voltage drop. Point A (Fig. 2-4A) placed in a liquid with a high electric resistance, such as mineral
is at a higher voltage than point B. When proceeding in the di oil (Fig. 2-3C). Mineral oil is a poor conductor because it con
rection of current across the resistor, the recording instrument tains few ions and, therefore, has a negligible electrical conduc
records a negative deflection. Moving from the negative to posi tivity (i.e., a high resistance). If an action potential is induced in
tive battery terminal across the resistor, opposite to the flow of a muscle or nerve fiber suspended in mineral oil, the local cir
cuit currents are restricted to the thin film of saline solution. 21
All current is then flowing along the immediate surface of the
A B cell and does not expand into the oil suspension. A referential
I- I electrode montage with the E-l electrode located in close prox
A ~ ~ imity to the tissue's surface records a monophasic negative
electrode is over the proximal extent of the negative sink (Fig. Waveform Morphologies in Large-Volume Conductors
2-3, C and D). We will now surround the nerve or muscle cell with a sub
Continued electrode movement results in meeting a current in stantially larger amount of saline and investigate the action po
the opposite direction coming from the trailing current source tential's extracellular morphology. To simplify the discussion,
heading into the current sink. It is important to note the relation again consider the action potential to be suspended at an instant
ship between the direction of electrode movement and current di in time, and move a referential recording electrode through. the
rection, i.e., now traveling in opposite directions. According to action potential's local circuit currents. In a good volume con
the resistor circuit model, when the current and electrode direc ductor, the local circuit current lines no longer immediately tum
tion of travel are opposite, a positive screen deflection ensues. In in toward the current sink, but first travel away from the current
our example, the trace deflection is indeed now heading in the sink and fan out an appreciable distance from the cell's surface
less negative direction (Fig. 2-3, C and D). The current density of into the volume conductor, and then head back into the current
the trailing local circuit current is less dense and has a greater spa sink (Figs. 2-2 and 2_5).54.83 Additionally, as one approaches the
tial extent accounting for the trace's comparatively slower return current sink from any direction, the current density increases
to baseline. As the trailing source current diminishes, the instru because the source currents are "focused" into the sink region.
ment's trace settles back to baseline. The net result in a poor The extracellularly recorded waveform morphology in a good
volume conductor is a monophasic negative extracellular wave volume conductor also may be explained with the assistance of
form produced by a monophasic positive intracellular potential. 21 the resistor circuit model (Fig. 2-5, A-D).32 The electrode
o o
Volume
Conductor
Level 3 (:30mm)
~WI2{5{O:?mml
Levell . 0=~m~m~I______~==~~~~~~~~~~;:~~:;2:=- ___________
Nerve
A B C D
;
-l ~ .."
It
"
Level I ., \!" 'V*'
1
100
T .,"
".'
!
'. "
.,~
.'
I
.,......
i
Level 2 11 '\.
"V
I
"f
'H
\f
•
'\
,
, iV
'.;
:
"
"
:
II
....
:
,,
, \
I
, .
: \
,,
I ,
, . I
..
,
,
\
Level 3 ..... "" .......... .,1
\:::::::..........
Figure 2-5. Action potential field distribution. Computer-simulated current field distribution surrounding a suspended action potential
propagating from right to left. Levels 1-3 represent sequential electrode positions and their accompanying waveforms (A through C) at progres
Sively greater distances from the nerve's surface. The three levels of recording were simulated at 0.5, 5.0, and 30 mm from the nerve. (From
Dumitru D:Volume conduction:Theory and application. In Dumitru D (ed): Clinical Electrophysiology. Philadelphia, Hanley & Belfus, 1989, pp
665-681. with permission.)
Chapter 2 ELECTRICAL SOURCES AND VOLUME CONDUCTION - II
moving from left to right first detects local circuit current lines To the right of the second zero isopotentialline, the current
moving out and away from the membrane's surface opposite the and electrode are still traveling in opposite directions and the
direction of electrode passage. A positive deflection results. The trace continues below the baseline. As the electrode continues
magnitude of the positive deflection grows as the electrode gets to proceed to the right, it is again perpendicular to the current
closer to the current sink. The peak of the positive deflection is flowing away from the membrane's surface and a third and final
achieved when the electrode is situated just perpendicular to the inflection point is noted. For the remainder of the action poten
local circuit current lines, i.e., when the current is neither travel tial, the local circuit current flows out from the membrane away
ing against nor with the direction of electrode movement. The from the current sink prior to curving back toward the mem
ions are not moving away from or toward the sink, but straight brane. In this region, the electrode and current flow move in the
up relative to the membrane's surface. When the electrode is same direction and the trace proceeds in the negative (less posi
over this perpendicular aspect of the current flow, the trace stops tive) direction toward the baseline. The current density then di
moving in the positive direction. Just to the right of this perpen minishes and the trace settles back to baseline. The end result is
dicular zone, the electrode is still in a region of high current a triphasic waveform: positive-negative-positive (Fig. 2-5 D).
density, but progressing in the direction of current flow. The A crucial notion is that the same intracellular positive
electrode in our example now moves into a region being less monophasic action potential produces different extracellular
positive than previously; this is reflected in the instrument's waveform morphologies depending upon the surrounding
trace now moving in the less positive direction and beginning to medium (Figs. 2-3D and 2-5D, Levels 1-3). In a restricted con
approach the baseline (Fig. 2-SA). ducting medium, a monophasic negative extracellular potential
With continued movement, the electrode encounters a zero is recorded, whereas in a large volume conductor, a triphasic
isopotet;ltialline, and the trace crosses the baseline. As the elec initially positive extracellular waveform is detected.
trode travels to the right of the zero isopotentialline, it continues This statement may be further conceptualized by considering
to detect a current moving in the same direction. The trace rises our previous example of a nerve coated with a thin salt solution
above the baseline. A negative potential is recorded (Fig. 2-SB). (Fig. 2-6). Initially, the local circuit currents are confined to the
The second inflection point is reached when the electrode is again immediate region surrounding the nerve's extracellular surface.
perpendicular to the direction of current flow. This time, however, The isopotential lines demarcating the current sink and its two
the current is flowing into the membrane as opposed to that of the source current regions, two zero isopotentiallines, essentially
first inflection point when it was flowing away from the mem hug the membrane's surface (Fig. 2-6A). If the amount of
brane's surface. Immediately to the right ofthis perpendicular volume conductor surrounding the nerve is moderately in
electrode/current flow relationship, the electrode again encoun creased, the local circuit current expands into the added region
ters current flowing toward it, signifying a region of diminishing and both zero isopotential lines move away from the mem
negative potential, thereby describing a less negative deflection branes surface with slightly more elevation for the leading
(Fig. 2-5C). With electrode advancement, the instrument's trace zero isopotential line because of the increased current density
continues in this direction until the second zero isopotentialline (Fig. 2-6B). The electrode now detects a portion of the initial
is encountered, at which time the baseline is again reached. positive current flow resulting in a positive deflection. Next, a
A ...._.............._._................... 11 mm
,) +0
c
11mm
Figure 2-6. Volume conductor Influence on waveform morphology. A. Nerve surrounded by a thin film of conducting medium similar
to that described in Figure 2-3. Note how the zero Isopotential lines are markedly curved so that only the negative sink portion of the action po
tential is capable of being detected by the recording electrode. The end result is a monophasic negative potential. a,Adding more conducting
medium allows the local circuit currents to expand further from the membrane's surface resulting in a concomitant elevation of both, but prefer
entially the leading zero isopotential Iines.A biphasic positive/negative potential ensues. C, Significantly increasing the surrounding volume conduc
tor permits the local circuit currents to move comparatively further from the nerve's surface fully exposing the leading and trailing positive source
currents to the recording electrode. The end result is the expected triphasiC waveform. (Modifled from de Weerd JPC:Volume conduction and
electromyography. In Notermans SLH (ed): Current Practice of Clinical Electromyography. Amsterdam. Elsevier, 1984. pp 9-28.)
34 - PART I FUNDAMENTAL PRINCIPLES
negative deflection is observed. The low density of the trailing action potential's characteristics for the first several action po
local circuit current with only a mild elevation of the zero isopo tentials generated. 109.1 10
tentialline allows a minimal, if any, trailing positive current to
be detected. The end result in this case is an initially positive
biphasic potential. Finally, if a sufficient amount of volume con WAVEFORM MORPHOLOGY IN NERVE
ductor surrounds the nerve, the zero isopotentiallines extend
away from the membrane's surface to allow complete recording SENSORY NERVE ACTION POTENTIALS (SNAPS)
of both the initial and trailing positive source currents, produc
ing a triphasic (positive-negative-positive) potential (Figs. 2-5 Clinical Recordings
and 2-6C). The waveform arising from a referentially recorded digital
As discussed above, the morphology of the extracellularly SNAP is triphasic (Fig. 2-7B). 8 The observed SNAP potential is
recorded waveforms depends upon the direction of travel for the the summation of triphasic waveforms from thousands of individ
electrode with respect to the current as well as the characteris ual nerve fibers each contributing a triphasic waveform, A nerve
tics of volume conductor present. The amplitude of the ob fiber's action potential approximates 0.5 ms in duration. This 0.5
served potential is directly related to the current density. 19.20 The ms intracellular monophasic action potential may result in an ex
current density decreases with an increase in distance from the tracellular triphasic waveform of about 2.0 ms in duration when
generator. Sequential electrode placement at distances further recorded in a good volume conductor because of the longitudinal
from the current generator results in potentials with an earlier local circuit current's spatial expanse preceding and following the
and smaller positive deflection, and a reduced negative peak negative sink.s If this potential propagates with a conduction ve
amplitude displaced toward the geometric center of current sink locity of 50 mfs, it has a spatial extent within the volume conduc
(Fig. 2-5, levels 1-3).54 The terminal positive phase is also re tor extending along the nerve for about 100 mm {NCV =Dff;
duced in magnitUde. These observations are a result of the 50,000 mmflOOO ms =D/2.0 ms; D = 100 mm}. As the sensory
wider, less dense, and more symmetric current field formed in nerve is composed of thousands of fibers with different conduc
the volume conductor further from the current generator. tion velocities, the result is an overlapping of multiple waveforms,
each with slightly different spatial distributions,?3 The composite
Waveform Asymmetry SNAP can have a duration of 3.0 ms and more (Fig. 2-7).
The triphasic appearance of extracellularly recorded poten
tials with a referential electrode montage near the generator's SNAP Morphology
source demonstrate a rather distinctive asymmetry (Fig. 2-5D). The morphology of antidromic and orthodromic bipolar
The triphasic waveform's first positive phase is larger in magni SNAP waveform recordings is typically biphasic and does not
tude and shorter in duration than the terminal positive phase. have the aforementioned triphasic waveform (Fig. 2-7A).8 The
Also, the time from the first positive peak to the subsequent neg
ative peak, rise time, is shorter than that from this negative peak
to the second positive peak. An intracellular nerve action poten
tial has a duration (T) approximating 0.5 ms89•90,113 and can prop
agate at a nerve conduction velocity (NCV) of 50 meters/second
(mfs), which produces a negative sink with a spatial extent (D) of
about 25 millimeters (mm) {NCV = Dff; 50 mfs = D/O.5 ms; D
= 25 mm}. Sodium activation (open Na+ channels) has a dura
tion of about 0.1 ms, which represents a spatial expanse along
the nerve of approximately 5 mm. Therefore, when the action B
potential is considered from a spatial perspective, most of the
Na+ channels are open for the first 5 mm of the current sink
while the remaining 20 mm (0.4 ms) of the current sink encom
passes repolarization, This observation suggests that the local
circuit current lines are spatially directed and compressed about
the initial portion of the propagating current sink; this is where
the Na+ gates are opened.54 The initial region of current compres
sion causes the local circuit current lines to fan out and flow
-.J20 Il V
1ms ~
/\
VD
away from the beginning portion of the current sink compared to
the terminal area. 21 This difference in current density is directly
reflected in the slope of the rise and fall of the intracellular action Figure 2-7. SNAP morphology. Median nerve stimulation at the
potential (Fig. 2-3A). Once the gates have closed, the potential is wrist with an antidromic sensory recording montage. Active (A) and
reduced by an effluxing current2.lt •67 (e.g., potassium) or a reference (R) recording electrodes are located on the third and fifth
sodium back leak. 3 •12 Therefore, the asymmetric extracellular digits. A. Bipolar recording results in a biphasic SNAP. B,Active elec
triphasic waveform results from the slope characteristics of the trode on the proximal third digit referenced to the fifth digit results in
intracellular action potential, which depends on the spatial distri a triphasic SNAP. C,When the active electrode is located on the fifth
bution of open sodium channels. digit and referenced to the distal third digit, an inverted and slightly de
Of interest, in a number of myelinated nerves, repolarization layed (compared to waveform in B) triphasic potential is observed. D,
does not occur through a potassium ion efflux, but through a Electronic summation of traces Band C yields the potential recorded
sodium ion back leak. 3,12.84,93 The potassium current is replaced in trace A (From Dumitru D:Volume conduction:Theory and applica
by an effluxing sodium current The blocking of potassium volt tion.ln Dumitru D (ed): Clinical Electrophysiology. Philadelphia, Hanley
age-gated channels produces no significant alteration in the & Belfus, 1989,pp 66S-681.with permission.)
Chapter 2 ELECTRICAL SOURCES AND VOLUME CONDUCTION - 15
biphasic, negative-positive potential is a result of the bipolar It is also possible to predict the optimum interelectrode sepa
recording technique and not a violation of the previously pre ration to maximize the biphasic potential's amplitude in a bipo
sented extracellular action potential properties. Biphasic SNAP lar recording montage. The critical factor in this instance is the
waveforms can be easily understood by investigating bipolar rise time, baseline to negative peak, of the biphasic potential.
and referential recording montages for median nerve stimula The recording electrodes must be located at a distance greater
tion at the wrist8 (Fig. 2-7). Initially, two ring recording elec than the spatial extent represented by the rise time's duration.
trodes can be placed on the third digit (bipolar montage) with The rise time of most SNAPs approach O.S ms,14 which repre
the E-l electrode (active electrode) proximal. When the median sents a longitudinal extent of 40 mm for a conduction velocity
nerve is excited at the wrist, a clearly biphasic response is ob of 50 mls {50,000 mmlIOOO ms = D/O.S ms; D 40 mm}. If the
tained (Fig. 2-7 A). Next, the distal E-2 recording electrode (ref two recording electrodes are separated by a distance less than
erence electrode) is relocated to the fifth digit that is innervated 40 mm, components recorded by one electrode will overlap
by the ulnar nerve, thereby precluding median nerve activity with those recorded by another electrode resulting in mutual
from influencing the potential at this electrode. This allows one cancellation (differential amplification) of those components
to record a median nerve response from the E-l electrode with and producing a potential with a smaller amplitUde. Continued
out any contribution from E-2. When the median nerve is again interelectrode separation toward 100 mm now approaches a ref
stimulated, the observed waveform is triphasic, positive-nega erential montage and the two triphasic potentials in Figure 2-7
tive-positive (Fig. 2-7B). One can conclude, therefore, that the Band C become detectable. The potential from E-l precedes
bipolar recording in some way produces the biphasic and not that from E-2, as the two electrodes no longer interact.
the expected triphasic waveform.
Continuing with the median nerve example, we can now Distance Effects on Dispersion and Phase Cancellation
place the E-I electrode on the fifth digit and keep the E-2 elec We can return to the bipolar antidromic recording example to
trode on the third digit's distal portion. This referential montage investigate the effect different stimulus sites have on SNAP con
should record electrical activity only from the E-2 electrode. figuration. Activating the median nerve at the wrist yields the
Following median nerve stimulation, an inverted (E-2 elec expected biphasic SNAP. Relocating the electrical stimulator
trode), somewhat smaller and slightly delayed triphasic poten sequentially at more proximal activation sites results in a series
tial compared to the previous triphasic waveform is observed of SNAPs with a progressively declining amplitude, and area to
(Fig. 2-7C). In essence, this is the same potential as that the negative phase (Fig. 2-S). This observation may be under
recorded in the referential montage of Figure 2-7B with several stood if one recalls that the duration of an intracellular action
exceptions. Specifically, the potential is (1) smaller because potential of a single mammalian nerve approximates 0.5 ms and
fewer nerve fibers are present more distally near the fingertip, results in an extracellular triphasic waveform of about 2.0 ms in
(2) a little more delayed temporally as more distance is tra a volume conductor. A bipolar recording of this extracellular
versed in reaching the finger tip, and (3) inverted because it is waveform results in a biphasic potential with a negative dura
fed to the amplifier through the inverting port (E-2). tion close to that of 0.5 ms. The negative spike of the individual
In the bipolar recording example above (Fig. 2-7A), the wave axon (about 0.5 ms) is approximately one-third of the whole
form from the fingertip is electronically added to the waveform nerve SNAP (roughly 1.5 ms).88
recorded at the digit's proximal portion. The waveform at the fin Another important factor is the range of conduction velocities
gertip approximates that from the more proximal location, but it between the fastest- and slowest-conducting fibers, which can
is inverted and slightly delayed in time. Adding one to the other be more than 25 mlS.27.28 This range in velocities results in tem
produces a biphasic potential. It is the slight temporal delay and poral dispersion and consequently in asynchronous arrival of
smaller amplitude of the distal potential that prevents mutual single-fiber action potentials at the recording electrode. 99 In
cancellation. The initial positive phase is eliminated and the neg combining the observation of relatively short action potential
ative peak amplitude is somewhat smaller and occurs slightly durations with the relatively large amount of temporal disper
earlier in time than for the proximal triphasic potential. This sion, a significant amount of overlap between the negative and
process can be simulated by electronically adding what the E-2 positive phases of individual axons occurs (Fig. 2-9). The over
electrode alone recorded (Fig. 2-7C) to the waveform obtained lap of positive and negative peaks produces phase cancellation
solely by the E-l electrode (Fig. 2-7B), resulting in what was resulting in a lower amplitude and area than might be expected
originally detected by the bipolar recording (Figs. 2-7D and 2 from the thousands of single nerve fibers excited. It can be seen
7A, respectively).8 Therefore, bipolarly recorded waveforms are that as the distance between the stimulus and recording sites in
usually biphasic because of the cancellation effect of some simi creases, more temporal dispersion and phase cancellation would
lar components being eliminated in differential amplification. be anticipated, thus producing progressively longer SNAP dura
In a bipolar montage, the recorded waveform only achieves tions and declining amplitudes and areas for SNAP potentials.
its full triphasic morphology and maximum amplitude when the This is indeed the finding in clinical studies.73-75.88
E-2 electrode contributes minimally to the response, i.e., the
electrode montage approaches a referential recording. The pre FAR-FIELD POTENTIALS
ceding example of an action potential with an extracellular
waveform 2.0 ms in duration propagating at 50 mls demon Evoked Potentials
strates that the minimum interelectrode separation required to A far-field potential is simply the waveform detected when
optimally resolve the triphasic waveform is just over 100 mm. both electrodes are located in the far field of the current's spatial
In this scenario, where the E-2 electrode is located 100 mm gradient arising from an action potential. Far-field potentials
from E-l along the nerve's length, it does not record any portion were first described in brainstem auditory evoked responses
of the neural impulse's waveform until it has completely passed (BAERs), which are waveforms generated from the auditory
the E-l electrode, thereby acting as a referential montage. pathway secondary to acoustic stimulation. 60 •61 ,86 Actually, not
However, few individuals possess a digit longer than 100 mm. all BAER potentials are far-field potentials because wave I is
36 - PART I FUNDAMENTAL PRINCIPLES
___f'\ ~-Iv-
-~t-,--~
p I,mv
5m~
V 120P~
5ms
'{,' l20pV
5ms
Figure 2-8. Distance effects on CHAP/SNAP waveforms. Simultaneous recordings of the CMAP from the thenar eminence and SNAP
from the second and third digits following stimulation of the median nerve at the palm. wrist, elbow. and axilla. Note that the CMAP declines min
imally, but there is a rather noticeable reduction in the SNAP's amplitude and area. (From Kimura J. Machida M, Ishida 1; et al: Relation between size
of compound sensory or muscle action potentials. and length of nerve segment. Neurology 1986;36:647~52. with permission.)
generated in the auditory nerve, and as a near-field, it is absent system. Interestingly, for wave II it has been elegantly shown
from the contralateral ear. For the other waves, it is true that the that it arises at the junction between cerebrospinal fluid and
neural generators are deep within the skull, and the recording brainstem due to the sudden change in conductivity of the
electrodes are located far from the current source on the skull's volume conductor,85 For the later components, the origin is
vertex and earlobes. 36 Seven potentials are usually produced in probably a dipolar field due to the dipolar source activity of
response to auditory clicks given to one of the ears. Lesions large clusters of neurons.
compromising the neural components of the auditory pathway. Far-field potentials also were described in somatosensory
e.g., multiple sclerosis or an acoustic neuroma, result in either evoked potential (SEP) recordings,'6,17.'8,23,24 Following exci
delayed or absent wavefonns. 98,'03 BAERs are, therefore. useful tation of a peripheral nerve, electrical responses can be
in the diagnosis of pathology involving the central nervous recorded over not just the distal limb, but also proximally in
.....
depicting phase cancellation effects resulting from in
creased distance and the results of differences be
,
#\
5 ----:-0--=.tf{.;i"'ff
o .un1 vr.. m
tween the fast and slow conducting nerve fibers.With
distal stimulation. the phases from the individual
SNAPs summate. whereas with increased distance
tht> phases separate enough by the time they reach
the recording electrodes to summate less or even
cancel. (From Kimura J, Machida M. Ishida T. et al:
Relation between size of compound sensory or
muscle action potentials. and length of nerve seg
ment. Neurology 1986;36:647~2. with permission.)
.
t
"
S t -11------ -,j \ .r-"
, u
Chapter 2 ELECTRICAL SOURCESANDVOLUME CONDUCTION - 17
the supraclavicular area, the cervical spine, and from the scalp A series of electrodes can be located along the course of this
overlying the somatosensory cortex of the brain. In short, an nerve and into the distal extent of the second digit beyond the
SEP may be thought of as simply conduction along a long anatomic distributiori of the nerve. An additional electrode may
nerve pathway for both the peripheral and central nervous be located on the fifth digit and should show no response when
system. Stimulation of the median nerve produces four posi the radial nerve is electrically activated. First, the series of adja
tive potentials preceding the arrival of the impulse at the so cent recording electrodes can be arranged in a sequential bipo
matosensory cortex. 23 •24 The interesting finding regarding the lar montage. The radial nerve is excited and a biphasic radial
far-field potentials is that they were all positive in polarity and nerve SNAP is obtained from each pair of electrodes (Fig. 2-10;
had the same respective latencies despite different electrode left panel). The SNAP's peak latency increases with each elec
locations. This observation suggested that these far-field po trode pair as the induced impulse propagates distally. These are
tentials were not localized phenomena, but extended an appre completely anticipated results. Secondly. each electrode along
ciable distance and appeared instantaneously throughout the the course of the nerve may be connected in tum to the fifth
body. Because the far-field potentials might facilitate diagno digit comprising a referential montage. In this instance, radial
sis of lesions affecting the somatosensory pathway, attempts nerve stimulation produces the anticipated triphasic waveform
were made to define their site of origin. Using SEP far-field with a progressively increasing peak latency. However, two
potentials to localize neural pathway pathology is a difficult non-moving positive and negative potentials with the same re
task because far-field generator sites do not always have a spective latency were noted despite different electrode locations
direct neurophysiologic basis, and variable waveform mor (Fig. 2-10; right panel). These referentially observed potentials
phology and latency can occur with alterations in body posi are by definition far-field potentials because they had a distribu
tion. 4 2,71,114 It is possible to gain an appreciation of far-field tion outside of the nerve's anatomic course, and did not change
potential properties from a number of interesting peripheral latency despite different electrode locations. 7o Comparing when
nerve experiments. the far-field potentials first appeared with the anatomic location
of the electrode determined the anatomic site for some of these
Peripheral Nerve Observations far-field generators. The forearm/hand junction (wrist) and
Let us consider an experiment involving the superficial radial metacarpophalangeal joint were suggested as sites of generation
nerve in the upper limb.7° This nerve is subcutaneous and sub for at least two of the observed far-field potentials. Additional
ject to both stimulation and recording from the mid-forearm peripheral nerve recordings with referential montages of both
into the proximal interphalangeal region of the first three digits. the hand and remainder of the upper limb produced a theory of
' _ _ _ _ _oe:::===_
( _ J )_( -.) t' .... (-1)- II
( .
(-1)_(_1)
)-(-,)
(., j -( 0)
~~===~ l-')- II
( .)- v
(.,) - II
(.2)-(.')
(.,)- v
( .)-(.1)
( •• )-( .1) (.:t) - v
(••)-(..) .,"-_JlI. ( ••)- v
(.,)-(.s)
.
( .,)-( )
(-')-(.7)
.. (+s)- y
( ...) - y
(.,)- v
( •• ) - II
1.0 ....
Dipolar RecordIng
Figure 2-10. Peripheral nerve far-field potentials. Sensory nerve potentials across the hand along the second digit in a normal subject
recorded antidromically after stimulation of the superficial radial nerve 10 cm proximal to the radial styloid. In a bipolar recording (left), the initial
negative peaks, N I (arrow pointing up), showed a progressive increase in latency and reduction in amplitude distally and no response was
recorded beyond -1.ln a referential recording (right), biphasic peaks, P I-N I and PII-NII (arrows pointing down), showed greater amplitude distally,
with a constant latency irrespective of the recording sites along the digit. The onset of PI extended proximally to the recording electrodes near
the wrist (small arrows pointing down), whereas PII first appeared at the base of the digit. (From Kimura J. Mitsudome A,Yamada 1; Dickins QS:
Stationary peaks from a moving source in far·field recordings. Electroencephalogr Clin Neurophysiol 1984;58:35 1-361, with permission.)
38 - PART I FUNDAMENTAL PRINCIPLES
far-field potential production that should apply to both the cen long as one of the electrodes is on the opposite side of the bound
tral and peripheral nervous systems as well as to muscle tissue. ary or measuring some portion of the voltage difference's near
It has been postulated that as a traveling wave of depolariza field, a far-field potential can be detected. A successful model to
tion reaches (1) an heterogeneity of a volume conductor, e.g., qualitatively explain far-field potentials has been developed and
wrist or shoulder, (2) transitions in extracellular conductivities of is known as the leading/trailing dipole model.26.63.65
the volume conductor, (3) a change in the anatomic orientation
of a traveling action potential, and/or (4) the origination and/or The Leading/Trailing Dipole Model
termination of excitable tissue, a voltage difference arises at An action potential can schematically be described as consist
these "boundary zones."26.63.68.69,71 The voltage difference, in the ing of a centrally located current sink flanked by two current
case of property changes in the volume conductor as an underly sources, i.e., source-sink-source (+ - +: a tripole). The intracellu
ing cause (see below) also referred to as boundary or junctional larly directed current entering through the sink region extends
potentials, temporarily exist and extend instantaneously both proximally and distally. There are two complete local circuit
throughout the volume conductor for the time an action potential currents in effect splitting the sink into two negative regions (Fig
passes through the transition region arising from one of the 2_3C).2,14,26,66 The traditional source-sink-source, therefore, can
above four conditions. As long as a referential montage is placed also be thought of as a source-sinklsink-source (+ -, - +: a linear
so that the two electrodes are encompassing the relevant bound quadrupole or double dipole).25,92 This double dipole is referred
ary, a far-field potential will be recorded. The electrode loca to as a leading and trailing dipole depending on the direction of
tion's importance cannot be underestimated. If both of the propagation. Each dipole produces a dipole moment, which is
electrodes are in the far-field, but on the same side of the bound the product of the individual charge magnitude and the charge
ary zone and record the same potential, a far-field waveform is separation. The two dipole moments of an action potential have
not observed. It is eliminated in differential amplification. As opposite directions and balance each other. 64 When an action po
tential encounters one of the four boundary conditions previously
described, the leading/trailing dipole moments no longer balance.
E·1
A It is the potential difference associated with a dipole moment im
balance that is recorded as a far-field potential.
E·2 --f) + + : I) Differences in Volume Conductor Size and Tissue
E·1 Resistances
B Let us consider an induced action potential as it traverses two
E·2 -f) +-; + I) cylindrical volumes (Fig. 2-11). Initially, the propagating action
potential is completely contained within the smaller cylinder
E·1
and its associated current field is also confined in this space.
C The leading and trailing dipole moments exactly balance each
E.2-f}
+--+
I) ----....r other with a net zero potential in the far field. No voltage is
measured between the two recording electrodes E-I and E-2.
The instrument's trace remains flat (Fig. 2-IIA). As the action
-J
E·1 potential continues to propagate, it will reach the transition zone
D between the two volumes. For this discussion, we will consider
E·2 ---f) +
I) that point in time when the entire leading dipole is in the large
cylinder while the total trailing dipole remains in the smaller
E·1 cylinder (Fig. 2-11B). The leading dipole's current field is also
E
E.2-f) I) -,)l preferentially located in the large cylinder, whereas the trailing
dipole's current field is confined within the smaller cylinder.
Realize that the two dipoles should be considered as current
sources. The current strength is not influenced by the extracel
Figure 2-11. Size changes producing far-field potentials. An lular situation. That means that the potential they set up is en
action potential represented by a leadingltrailing dipole propagates tirely dependent on the resistance in the extracellular medium
along a nerve from the small to the large cylinder. A, The nerve is con· (Ohm's law: voltage = current x resistance).62 The resistance in
tained within the small cylinder and the differential amplifier does not the smaller cylinder is higher than that in the large cylinder. In
record a potential with the trace remaining flat. a,An instant in time the situation of Fig. 2-11 B the two dipoles are not completely
when the leading dipole is in the large cylinder while the trailing dipole balancing each other in the extracellular potential. In Figure 2
is still within the small cylinder. The amplifier records a potential differ liB an arbitrary magnitude is recorded between the E-l and the
ence from an imbalance in the dipole moments and the trace de E-2 electrodes in the far field. Continued impulse propagation
scribes a positive deflection. C, Continued neural propagation again results in both the leading and trailing dipoles now completely
allows the leading and trailing dipole moments to balance when the entering the large cylinder (Fig. 2-11 C). At some distance
nerve is completely within the large cylinder and the amplifier records beyond the boundary zone (several radii of the small cylinder),
no potential with a flat trace. D. The leading dipole has been extin the leading and the trailing dipole set up the s;'me (lower than in
guished at the nerve's end while the trailing dipole is still present.An the small cylinder) potential difference between E-! and E-2.
imbalance in dipole moments is again recorded by the amplifier and The potentials set up by the two dipoles are again balanced
the trace moves in the negative direction. E,When the impulse is no since the extracellular resistances with respect to the leading
longer present, the trace returns to baseline.Two far-field monophasic and trailing dipoles are equal again.
potentials of opposite polarity is the net result in the above combina Instead of changing the size of the volume conductor, one can
tion of boundary conditions. also consider a situation in which the specific resistance of the
Chapter 2 ELECTRICAL SOURCESANDVOLUME CONDUCTION - 39
(bent nerve) producing the far-field potential. If the E-l and E-2 capable of reaching the muscle membrane's threshold level. As
electrode locations are reversed, they will record potentials with a result, the depolarization is localized to the endplate region
the same magnitude but of opposite polarity to the above exam and represents a miniature endplate potential (MEPP).
ple. This observation implies that the polarity of the far-field po Clinically, multiple MEPPs are usually observed with an intra
tentials depends on the orientation of the electrodes and not the muscular recording electrode and the sound is referred to as
direction of impulse propagation. 1OO This principle should apply endplate noise or a "sea shell murmur." Numerous MEPPs. are
to all far-field-causing phenomena. As in the case of the action detected despite a firing frequency of 0.2 Hz per endplate be
potential termination, we here again have a "real" temporally ef cause the recording electrode is relatively large with respect to
fective dipole in the source characteristics causing the far field. the endplate region and detects multiple endplates firing simul
taneously (Fig. 2-13B).
A
0
+
0
:JL
J
+
+
B
B
Because the tenninal source current is effectively compressed negative trace deflection suggests that the current sink is pass
between the current sink and the endplate zone, it must "fit" into ing by the electrode. A complete absence of a tenninal positive
a smaller area that may tend to increase the trailing source's cur phase implies that the final source current never passed by the
rent density. An increased current density usually results in a recording electrode. This would suggest that a biphasic initially
larger potential. The decreased density of the trailing source positive potential could occur if a muscle action potential pos
current further along the fiber results in a comparatively smaller sessed leading source and sink currents but not a term\nal
final positive phase. The combination of a small tenninal posi source current with respect to the recording electrode. This pos
tive phase and baseline noise may at times prevent recording the sibility might occur if an action potential propagated up to, but
third phase allowing the wavefonn to appear biphasic. 30.43.96 not past, the E-1 electrode because the electrode damaged the
Considering bioelectric source and volume conduction con fiber rendering it incapable of sustaining an action potential past
cepts, a biphasic, initially negative potential could be produced if the injury point. A waveform recorded from an injured muscle
the E-l recording electrode were located in the area of muscle fiber may produce a biphasic initially positive potential. A
where the current sink is generated. In this situation, the elec second situation with similar results might occur if the record
trode will first detect the intracellularly directed Na+ current pro ing electrode is placed in proximity to the musculotendinous
ducing a negative trace deflection. As the current sink progresses region. 1,41 Again, the source and sink currents would approach
bidirectionally out into the muscle fiber, the recording electrode and reach the recording surface of the electrode. The tenninal
observes the two tenninal source currents and records a positive source current, however, would dissipate as soon as the current
deflection. The final potential recorded is a biphasic potential sink was extinguished as it encountered the tennination of ex
with an initial negative phase. We have already described poten citable tissue (muscle's tendon).
tials with a similar appearance arising because of terminal nerve
irritation from the electrode as opposed to voluntary contraction, MOTOR UNIT POTENTIAL MORPHOLOGY
i.e., endplate spikes. Placing a recording electrode in the end
plate zone, therefore, and eliciting a voluntary contraction results Anatomy. One anterior hom cell gives rise to a peripheral
in the expected biphasic single-muscle-fiber potentia!s.43.96 nerve fiber that splits into multiple terminal sprouts, each of
A positive deflection of the trace suggests that the source cur which innervate one muscle fiber (Fig. 2-17). The anterior hom
rent is approaching the recording electrode. The subsequent cell, its peripheral nerve, and all the single muscle fibers sup
plied by that nerve is referred to as a motor unit. 21 When the
anterior hom cell fires, or the axon that arises from it is stimu
lated, all of the muscle fibers belonging to that motor unit depo
cb
larize. The electrical activity from all these muscle fibers
summate to produce a motor unit action potential (MUAP).
A ...'-.. The anatomic distribution of the tenninal axon sprouts with re
, " spect to the muscle fibers they innervate is quite interesting and
particularly relevant to the morphologic characteristics of the
6mm MUAP.
The length of an individual terminal axon sprout from the
cD
point it divides to the endplate is quite variable for each muscle
fiber innervated. As a result, the spatial extent of the endplate
B ...... -.
' " region from one motor unit approximates 5 mm longitudinally
, " along the muscle.4-6·50 Additionally, the muscle fibers of a single
motor unit are randomly distributed in an oval territory approxi
mately 4-6 mm in diameter (Fig. 2-17). The random distribu
tion implies that the single muscle fibers may be in groups of
different numbers or singly arranged within the 4-6 mm. Five to
ten different motor units may share this area. The muscle fibers
constituting a single motor unit are randomly interspersed with
the muscle fibers of the other motor units sharing its oval terri
tory, When considering the morphology of a motor unit poten
tial with respect to volume conduction, one must consider the
'cD"
D'" ',.,'
, .
(1) geometric arrangement of individual fibers not only to each
other but neighboring fibers as well, (2) maximum spatial dis
placement between the two ends of a motor unit's endplate
region, (3) length of the tenninal axon sprouts, (4) relationship
of the recording electrode to the various groups of motor unit
fibers (Fig. 2-17 A-D), (5) conduction velocities of tenninal
axons and muscle fibers, and (6) neuromuscular junction trans
~20IJV
5ms mission times.
Amplitude/Rise Time. The morphology of a MUAP can be
Figure 2-17. Motor unit territory, Muscle fibers belonging to one described in terms of its amplitude (maximum peak-to-peak
motor unit are randomly distributed within a 6-mm oval territory. trace displacement), rise time (temporal aspect of a potential's
Four separate MUAP waveforms (aU representing the same motor peak: duration of initial positive to subsequent negative peak or
unit) are recorded from four (A-D) different locations close to (A) or baseline to negative peak), duration (departure from and return
within (B-D) the motor unit. to baseline), and number of phases (baseline crossing plus one)
Chapter 2 ELECTRICAL SOURCES AND VOLUME CONDUCTION - 4)
J
+ CMAP
o
.;
~~~~~~~---r~~~~~--~~~ CMAP
Figure 2-22. Biphasic CMAP. A,A surface electrode is located over the endplate region of a skeletal muscle. Activation of the peripheral
nerve supplying that muscle results in a current sink being generated in the endplate zone. The trace describes an initial upward or negative de
flection. B, Propagation of the muscle action potentials allows the recording electrode to detect their terminal source currents and produce a
positive deflection which eventually settles to baseline for a MUAP.A summation of those MUAPs from all of the more or less synchronously ex
cited nerve fibers leads to a biphasic negative-positive CMAP.
negative deflection. This situation may arise from trauma to the the abductor digiti minimi and stimulating the ulnar nerve. 40 A
area distorting the muscle tissue, profound muscle atrophy, or similar appearing potential, intramuscular nerve action po
attempted recording from a muscle with a poorly defined motor tential, may be observed with a recording electrode located a
point, such as some of the circular facial muscles. bit more distally than that over the abductor pollicis brevis'
If the CMAP is recorded with a high amplifier sensitivity motor point. g This muscle can have a rather diffuse region
(500-1,000 !..lVIdivision) from the thenar or hypothenar mus which can generate a CMAP with an initial negative deflection,
cles, a small (l0-50 !..lV) negative waveform preceding the thus accounting for a similarly appearing potential preceding
CMAP can be seen (Fig. 2-24).3! This potential can create a sit the CMAP with a distinctly different origin. The intramuscular
uation in which a small positive deflection appears to precede nerve action potential arises from the recurrent branch of the
the CMAP, causing the investigator to incorrectly conclude that median nerve in the midpalm region.40 This response is a near
E-l is not on the motor point. This negative waveform is the 80 field potential as opposed to the premotor potential which is a
called premotor potential. 8.3 ! The premotor potential originat far-field potential. The best course of action is to recognize the
ing from the thenar muscle group to median nerve stimulation premotor potential for what it is, and then measure the latency
has been extensively investigated. Investigators have demon to the take-off of the large negative potential initiating the
strated that the potential is derived from sensory fibers.1 9 The CMAP. Of course, one must ensure that the E-I electrode is op
premotor potential to the thenar eminence has also been claimed timally placed over the motor point prior to concluding that all
to be the palmar cutaneous branch of the median nerve, but this possible positive deflections are the premotor potential.
has been refuted. 3! Although the origin of this potential is some Just like SNAPs, distally recorded CMAPs may also demon
what in dispute, it arises from the sensory branches innervating strate a decrement in amplitude and area with more proximal
various portions of the palmar aspects of the hand. 47 The premo stimulation sites, but the magnitude of this drop does not ap
tor potential is in fact a far-field potential arising from the sen proach that seen in SNAPs. The duration of a single-muscle
sory branches innervating the thumb as they pass from the fiber action potential is substantially longer than that of a single
relatively flat volume of the palm into the cylindrical volume of nerve fiber. As previously stated, the individual muscle fibers
the first digit. 40 This situation also occurs when recording over belonging to one motor unit are separated by terminal nerves of
Chapter 2 ELECTRICAL SOURCESANDVOLUHE CONDUCTION - 47
500~V/cm
200~V/cm
50~V/cm
FAR-FIELD POTENTIALS
One may assume that obvious volume conduction phenom
ena should pertain to not only neural, but muscular tissue as
well. It may be reasonable to conclude that if far-field potentials
Figure 2-23. Triphasic CHAP.A,The surface electrode is located are produced in nerves, they also may be generated in muscles.
to one side of the muscle's motor point. Upon depolarization of the Computer simulations have predicted that muscle far-field po
nerve innervating the muscle, some portion of the source current may tentials should occur.5O The leading/trailing dipole model pre
be detected by the electrode. An initial downward deflection of the dicts that whenever the leading and tailing dipole moments do
trace results. B, Subsequent propagation of the muscle's action poten not balance, a far-field potential should be observed. This situa
tials then produces the expected local circuit sink and terminal source tion could be predicted to occur when a muscle action potential
currents. C, The final result is a waveform that is triphasic with an ini extinguishes at the musculotendinous junction. Indeed, far-field
tial positive deflection of the trace. muscle potentials have been demonstrated in the human biceps
muscle (Fig. 2_26).34,101 The explanation is essentially the same
as previously elucidated in the examples on nerve conduction.
different lengths and comprise an endplate with a certain
amount of spatial expanse. This separation of endplates and dif FIBRILLATION POTENTIALS
ferent lengths of nerve fibers results in some desynchrony at the
recording site even when the different muscle fibers are simulta When a muscle fiber is no longer in contact with its nerve
neously activated. After excitation of the motor axons, all of the supply, the resting membrane potential begins to oscillate
muscle fibers innervated by those nerve fibers depolarize and toward the threshold level. As threshold is reached, the single
the sum total of voltages add both spatially and temporally to muscle fiber spontaneously fires at regular and sometimes irreg
form the CMAP. The net result is a temporal and spatial disper ular rates ,9, 10 and an action potential propagates from the end
sion of the waveforms arising from the depolarized muscle plate region or possibly other sensitized areas along the length
fibers. The dispersive effects of time and distance produce a of the fiber (fibrillation).lo,lOs,l06 Fibrillation potentials are
phase cancellation effect at the motor unit level and result in simply spontaneous depolarizations of a single muscle fiber and
MUAPs with a negative spike duration approaching 5-6 ms. 88 will demonstrate waveform morphologies similar to those ex
Motor nerve conduction velocities display about half the tempo pected of single muscle fibers voluntarily activated. Fibrillation
ral distribution (12-13 mls) of sensory fibersP.2 8 Because of the potentials may not only occur spontaneously but also after elec
longer duration of MUAPs, compared to single-nerve-fiber po trode movement in pathologic tissue. Characteristically, the fib
tentials and this relatively little temporal dispersion of the indi rillation potential is of short duration (less than 5 ms), less than
vidual motor axons (Fig. 2-25), a CMAP with essentially the 1 mV in amplitude, and can fire at rates between 1-15
same duration and only little decrement following more proxi time/second (Hertz, Hz). They have a typical high-pitched
mal activation is seen. That CMAP generation can be quite "tick" sound like "rain on a tin roof' if amplified through a
complicated in a realistic situation can be nicely illustrated in 10udspeaker.1O A recording electrode located in the endplate
48 - PART I FUNDAMENTAL PRINCIPLES
Individual Summated
responses response
F f~ 0 lfV ,
,
S~? 0 ~'1) 0
,,
'- '
F~~ t &I~
S~t 0) t------
,,
,
,
,
Figure 2-25. CMAP phase cancellation. Stimulating the nerve distally (open arrows upper traces) results in the discharge of two MUAPs
with a slightly different latency after the stimulus that summate to produce a CMAP with approximately double amplitude. Proximal stimulation
(closed arrows lower traces) again results in two CMAPs that still summate in phase because of the long duration of the MUAP's negative phases.
The temporal dispersion of individual action potentials only minimally alters the CMAP. (From Kimura J, Machida M, Ishida 1; et al: Relation be
tween size of compound sensory or muscle action potentials, and length of nerve segment. Neurology 1986;36:647-652, with permission.)
zone of a denervated muscle records biphasic fibrillation poten recording electrode outside of the endplate zone, but far from
tials similar to the normal endplate spikes already discussed. A the tendinous region detects either biphasic (positive-negative)
or triphasic (positive-negative-positive) potentials. Approxi
mately 30% of fibrillation potentials are triphasic. 9.10 The fibril
lation potential may appear biphasic and initially positive if
recorded from the musculotendinous junction. The same
volume conductor explanations applied to single muscle fibers
can again be used for the fibrillation potential. A more detailed
explanation of fibrillation potentials is provided in the appendix
to this chapter.
motor endplate
----.-.
POSITIVE SHARP WAVES
Jasper and Ballem first described a potential recorded from
16mm denervated muscle with a large primary sharp positive deflec
tion followed by a small or absent negative potential and called
120~v it the positive sharp wave (PSW).57 This waveform is believed
I-----i
to have the same clinical significance as the fibrillation poten
1Sms tiaIP9,81,84 The true nature of the positive sharp wave is not yet
fully explained, but bioelectric source and volume conductor
tendon theory can be used to speculate on the possible nature of this in
teresting and clinically useful potential. Previous discussion
Figure 2-26. Muscle far-field potential. Measurement of the spa suggests that a positive trace deflection implies that a source
tiotemporal profile along the skin surface of a motor unit action po current is approaching the recording electrode, A subsequent
tential of the biceps brachii muscle. An array of 16 surface electrodes small negative potential indicates that the initial aspect of the
is located in parallel with the main direction of the fibers. The E-2 elec current sink is detected by the recording electrode, Simply, the
trode for all signals was placed on the ipsilateral elbow. Note the prop action potential approaches, but does not or just barely reaches
agating character of the main negative (upward) peak in two directions the electrode's recording surface, It has been suggested that the
starting at the end plate region (7th electrode) and the non-moving pathologically involved muscle fiber is adversely affected by
positive far-filed peak at the end of the waveform at all locations indi the deforming forces of an intramuscularly placed electrode
cating the extinction of the tripolar current source profile. (From such that a region of perielectrode conduction failure is in
Stegeman DF, Dumitru D, King JC, Roeleveld K: Near- and far-fields: duced,9 The positive sharp wave, therefore, may be a "blocked"
Source characteristics and the conducting medium in neurophysiology. fibrillation potential that cannot conduct past the recording elec
J Clin Neurophysiol 1997; 14:429-442, with permission.) trode (Fig. 2-27). This explanation, however, suggests that the
Chapter 2 ELECTRICAL SOURCES AND VOLUME CONDUCTION - 49
.. Direction of Trovel
A
Waveform
.:
,/~-~
.......---------''''""~ . . J f L - - - - - - - - . . J +"\
..:i
I.
I'
I'
::
~
Figure 2-27, Positive sharp wave. The generation of a positive sharp wave using volume conduction theory. A, The local source currents of a
fibrillation (single muscle fiber) approach a monopolar recording electrode (M) placed against a single muscle fiber.The initial source current is de
tected resulting in a positive trace deflection. The needle has caused a portion of the single muscle fiber to be compressed and no longer capable
of conducting action potentials (hashed region). B, Only a portion of the current sink can reach the recording electrode, resulting in a small nega
tive trace deflection. C, Because the current sink dissipates, the trace settles back to baseline describing a primarily positive potential or positive
sharp wave. (From Dumitru D:Volume conduction:Theory and application. In Dumitru D (ed): Clinical Electrophysiology. Philadelphia, Hanley &
Belfus, 1989, pp 665-681, with permission.)
PSW would have a duration no longer than that of a fibrillation and invert the negative spike (cannula = E-2), making it appear
potential instead of 2: 20 ms. Occasionally short-duration PSWs positive and thereby potentially simulating a positive sharp
can be observed and this may be the likely explanation, i.e., a wave. 76 The above three potentials can be distinguished from a
blocked fibrillation potential. A more detailed explanation of positive sharp wave in that they are MUAPs and subject to vol
the PSW is provided in this chapter's appendix. untary control, whereas a positive sharp wave is not. Asking the
Amplified through a loudspeaker, positive sharp waves have patient to contract and relax the muscle under investigation
a regular firing rate (1-20 Hz) that sounds like a dull thud and should result in a positive potential with variable firing rate,
can have durations of between several milliseconds to 100 ms. while a positive sharp wave typically fires regularly. If any
Although observed to fire spontaneously, PSWs also can be pro doubt remains, the electrode should be repositioned.
voked by electrode movement. Continued research into this fun
damental and interesting potential is required to more fully
elucidate its true pathophysiologic basis.41 PITFALLS AND POSSIBLE SOURCES OF
A number of other potentials can be observed that have a ERROR
morphology similar to a positive sharp wave but may have dis
tinctly different origins. As we have already described, a MUAP STIMULATION
recorded from the tendinous region also can have an initial pos
itive deflection followed by a negative potential because the A nerve is usually stimulated by electrodes located on the
current sink cannot pass beyond the recording electrode. 66 It is skin surface. The cathode produces a depolarizing current,
highly possible for the recording electrode to damage a number which is passively conducted through the skin into the human
of muscle fibers in close proximity to the recording surface pro body. A portion of this current excites neural tissue in its vicin
ducing action potential blockade. An additional possibility is for ity provided the current strength is sufficient to depolarize the
the cannula of a concentric needle recording electrode (see nerve fibers to threshold. The induced current exits the body at
Chapter 3) to be preferentially located in the motor unit territory the anode. Although it is theoretically possible to prevent neural
50 - PART I FUNDAMENTAL PRINCIPLES
conduction at the anode because of a hyperpolarizing current In addition to a longitudinal spread of the current field, a
about the anode, anodal block, the nerve is seldom prevented radial expansion of the depolarizing current also may be antici
from conducting an impulse past the anode. Anodal block has pated, particularly when using high stimulus intensities. An in
been shown to not occur during routine electrodiagnostic medi creased radial distribution of current can excite neighboring
cine studies. 29 In fact, the anode can actually depolarize the nerves, especially in small anatomic regions containing numer
nerve and possibly excite it at an unanticipated location leading ous nerves such as the wrist. Coactivation of multiple nerves
to confusion with respect to latency measurements and conduc leads to the depolarization of numerous muscle groups, includ
tion velocities (see Chapter 3). It is important to recognize that ing ones that might obliterate the desired response. This possi
the site of neural excitation and location of the superficially ap bility is demonstrated with an actual case in which the
plied cathode only correspond with weak stimulus intensities individual sustained significant trauma to the ulnar nerve in the
approximating 4 milliamperes (mA).s If we assume a standard forearm. An absent ulnar nerve SNAP and very small CMAP
distance of nerve conduction, elevating the current's intensity to was obtained with activation of the ulnar nerve. These findings
a supramaximal stimulus level (15-20 rnA), 20% greater than suggest profound axonal degeneration that was confirmed by
that required to excite all of the nerve's largest fibers, the site of profuse fibrillation potentials and positive sharp waves with
activation is displaced approximately 3 mm from the cathode. s only a few MUAP detected with a needle electrode in the first
The nerve is excited away from the cathode resulting in a reduc dorsal interosseous and ulnar innervated hypothenar muscles.
tion in conduction time (the "virtual cathode" effect). Fre Stimulating the median and ulnar nerves in the mid-palm region
quently, pathologic nerves require higher stimulus intensities while recording over the same nerves at the wrist l02 revealed in
for activation occasionally approaching 60 rnA, which can po teresting results (Fig. 2-28, A-D). Excitation of the ulnar nerve
tentially displace the site of neural excitation 12 mm.s If undue over the fourth palmar interspace while recording over the ulnar
current spread along the nerve is suspected, this potential source nerve proximally, resulted in an apparent normal response. This
of error regarding the exact location of axonal excitation can be result is inconsistent with profound axonal loss in the ulnar
reduced if a needle cathode is used. The near-nerve cathode en nerve and requires an explanation. Stimulating the median
sures a lower stimulus intensity as current is no longer re nerve in the second palmar interspace but recording from the
quired to pass a long way through the volume-conducting tissue. ulnar nerve at the wrist also produced a normal waveform.
It also diminishes artifact from the stimulating pulse itself, and Again, activating the fourth interspace but recording from the
better localizes the desired site of neural activation. A monopo median nerve yielded a normal appearing potential. Finally,
lar needle (see Chapter 3) is recommended as the cathode. stimulating the second interspace and recording over the median
nerve also produced a normal waveform. Given that the ulnar
nerve is pathologically involved, it is reasonable to conclude
that stimulating the fourth interspace with sufficient current did
not activate the ulnar nerve, but actually depolarized the nearby
median nerve in the palm. Once the median nerve was excited,
A it followed its normal course and produced the expected re
sponse at the wrist. Additionally, the current field in the fourth
palmar interspace activated the median nerve. The resulting
B median nerve waveform at the wrist was of a sufficient magni
tude to radially spread to the electrode located over the ulnar
nerve producing a potential at this site following a fourth palmar
interspace stimulus. In pathologic and occasionally normal oc
casions, it is important to be aware of the stimulating current
strength to avoid a volume-conducted extension of the depolar
c izing current and its resultant neural or muscular response that
extends to unintended regions of the body.
RECORDING
It is important to understand that placing an electrode on the
skin over a specific muscle does not ensure that the only re
o sponse detected will arise form the intended tissue. Recall from
the preceding section that if the depolarizing stimulus is strong
enough, multiple nerves can be activated. Also, it has already
Figure 2-28. Volume conducted stimulation and recording. been pointed out that a positive deflection may precede the an
Median and ulnar nerve palmar stimulation with wrist recording over ticipated biphasic negative-positive CMAP. Relocating the
the median and ulnar nerves. A, Stimulation of the fourth palmar inter active electrode over the muscle's motor point eliminates the
space and recording over the ulnar nerve at the wrist. B, Excitation of initial positive phase as the recording electrode is now directly
the second palmar interspace with the same recording montage as in over the current sink.
A. C, The fourth palmar interspace is stimulated and the recording The possibility of multiple CMAP waveforms summating in
electrodes are placed over the median nerve. D, Stimulating the the volume conductor of the body can be reduced by placing a
second palmar interspace with the same recording position as C.A recording electrode intramuscularly.48 This ensures that the ma
large current intensity was used to obtain all responses. (From jority of the investigated waveform is arising from excitable
Dumitru D, Delisa JA: Volume conduction. Muscle Nerve tissue immediately surrounding the electrode. The observed
1991; 14:605-624. with permission.) CMAP amplitude, however, is no longer an accurate reflection
Chapter 2 ELECTRICAL SOURCES AND VOLUME CONDUCTION - 51
~5000~V J10mv
2ms Sma
~-----
Amplitude
B Latency Peak
Trace Baseline
onset to
to peak
peak
ms mV
Figure 2·29. Volume conducted recording. A, Recording of a A 3.5 11 21
CMAP with the active electrode on the midpoint of the first dorsal in B 3.5 5 9
terosseous muscle and the reference electrode on the second
metacarpophalangeal joint. B. Relocating the reference electrode to
Figure 2-30. Effect of reference electrode. A,Active electrode
the first metacarpophalangeal joint.
located on the motor point of the abductor pollicis brevis and refer
ence electrode placed on the distal aspect of the first digit. B,
of the total number of muscle fibers activated within the Relocating the reference electrode onto the muscle tissue. (From
muscle. 56 This is because the intramuscular recording electrode Dumitru D. Walsh NE: Practical instrumentation and common sources
has a more limited recording area and is preferentially influ of error. Am J Phys Med Rehabil 1988;67:55-65, with permission.)
enced by the tissue in the immediate vicinity of the small
recording surface.
In addition to accurate placement of the E-} recording elec that there is a possibility of axonal loss when indeed the small
trode, equal attention must be given to the location of the E-2 or amplitude is an artifact from poor recording techniques in a
reference electrode. Remember that the E-2 electrode should be volume conductor. The primary factors in electrode placement
of a sufficient distance from the E-l electrode so as to not for CMAP observations is to place E-! on the motor point, and
record similar data because this impairs the differential amplifi E-2 away from the tissue to be excited; the 4-cm30 separation
cation (see Chapter 3). In the volume conductor of the body, the used in SNAP recordings becomes irrelevant for motor studies.
E-2 electrode is just as capable of recording source and sink The most important factor is to ensure a reference location away
currents as the E-} electrode. This possibility can be easily from active tissue to reduce volume-conducted potentials, but
demonstrated by a simple example. Let us suppose that a close enough to take advantage of common mode rejection of
recording of the first dorsal interosseous (FDI) CMAP is de environmental noise. In the hand, for example, plaftng the
sired. The E-! electrode is located over the midpoint of this active recording electrode on the thenar eminence and the refer
muscle in an attempt to record from the motor point. It is now ence electrode on the metacarpophalangeal joint satisfies both
necessary to place the E-2 electrode in a convenient location, requirements.
such as the second metacarpophalangeal joint region. In volume conduction, recording from and stimulating ex
Stimulating the ulnar nerve at the wrist results in an initial posi citable tissues is a trade-off. Enough stimulation must be used
tive deflection (Fig. 2-29A). The possibility arises that E-l is to excite all of the fibers within a nerve, but not enough current
not on the motor point and so it is relocated to several locations to coactivate multiple nerves resulting in too many tissues depo
to no avail; the initial positive phase persists. Upon moving the larizing. Interpreting waveform recordings can also be haz
reference electrode to the first metacarpophalangeal joint ardous as many tissues overlap in the volume conductor of the
region, the desired biphasic negative-positive CMAP with a body and cannot simply be ignored. Localized intramuscular
slightly reduced amplitude compared to those obtained previ recordings can usually assure one whether a specific muscle has
ously is observed (Fig. 2-29B). It should now be obvious that depolarized, but the amplitude recorded less well reflects the
the E-2 electrode records a CMAP from an unintended muscle muscle as a whole.
that is activated prior to the FDI. Because the first activated
muscles were recorded from the reference electrode, they pro
duced a positive deflection. The source and sink currents from CONCLUSION
the multiple muscles activated to summate somewhat, causing
the CMAP with an initial positive phase to be larger than the An appreciation of the principles discussed in this chapter
biphasic response CMAP. This example suggests that the refer permits the practitioner the ability to better comprehend the
ence electrode contributed to the CMAP. generation of the morphology of any waveform observed. This
It is necessary to realize that the majority of electrodes are knowledge is of use in not only identifying specific potentials,
relatively small compared to the muscles from which they are but gaining insight into their generation in both normal and
recording. Locating both electrodes over the muscle to be acti pathologic situations. It is possible to use volume conduction to
vated can produce CMAPs with amplitudes smaller than antici one's advantage by systematically applying the knowledge
pated (Fig. 2-30). A small amplitude may cause one to conclude gained in this chapter. On the other hand, the unsuspecting or
S2 - PART I FUNDAMENTAL PRINCIPLES
uninfonned clinician is subject to multiple potential errors with 28. Dorfman LJ: The distribution of conduction velocities (DCV) in peripheral
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30. Dumitru D, Walsh NE: Practical instrumentation and common sources of error.
Am J Phys Med 1988;67:55-65.
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Appendix
APPENDIX OUTLINE
The leading/trailing dipole (L/fD) modefI gives a deceptively relatively close to an active fiber. When an electrode records
simple yet powerful explanation for many electrophysiologic phe electrical activity close to the tissue of interest, the waveform
nomena. We may characterize nerve or muscle fiber electrical ac can be referred to as a near-field waveform. 21 We will also
tivity as consisting of a central negative current sink surrounded discuss far-field waveforms and sources after the groundwork
and supplied by positive current sources. Since the majority of for near-field sources and their associated waveforms have
action potentials propagate for at least a short time during their ex been described.
istence, a direction of propagation is implied. This directional For the purposes of this discussion, the LrrD model will be
quality stems from the fact that action potentials begin at some de described with respect to muscle fibers only. However, the same
fined location and extinguish at another. In addition to propagation principles apply to nerve fibers as well. We may begin by con
direction, action potentials also have spatial characteristics, i.e., sidering an innervated single muscle fiber with a neuromuscular
they span a defined section of the sustaining nerve or muscle fiber. junction located midway between the fiber's two musculotendi
These two action potential qualities permit one to use a two-di nous junctions (Fig. I). Initially, the opening of acetylcholine
mensional action potential description whereby its central (nega receptors produces an inwardly directed sodium ion current
tive) sink region is flanked by a leading (direction in which the forming a negative voltage current sink (Fig. IA). The sur
action potential is heading) and trailing (direction from which the rounding region of muscle membrane acts as the positive volt
action potential originated) positive source, creating the traditional age source "feeding" the negative sink, thereby generating the
tripole (+ - +) model. I6 For conceptual convenience, the tripole growing quadrupole (+ - - +). This quadrupole grows in magni
(+ - +) is converted into a quadrupole (+ - - +) with a designated tude as the sodium current maximizes (Fig. IB). A recording
leading dipole (LD: + -) and a trailing dipole (TD: - +). Finally, electrode is positioned directly over the neuromuscular junction
this quadrupole is spread out over a region of membrane creating region with a distant reference electrode forming a so-called
a spatially distributed compound source (the LrrD model). "referential" or monopolar recording montage. This electrode
records the initial negative voltage, which results in a negative
or upwardly directed deflection on the recording oscilloscope
NEAR-FIELD WAVEFORMS (Fig. lA and B; E-IA). The negative deflection continues to
grow in magnitude proportional to that of our developing nega
INNERVATED MUSCLE FIBERS tive sink. Action potential propagation from the neuromuscular
junction out onto the muscle membrane results in the action po
The LlTD model will first be used to describe a number of tential's trailing dipole (TD) becoming manifest about the neu
anticipated waveforms recorded with an electrode positioned romuscular junction coincident with membrane repolarization
54
Appendix THE LEADINGITRAILING DIPOLE MODEL AND NEAR-FIELD/FAR-FIELDWAVEFORMS - 55
...
1 2
A
A
~10J.lV
B 2ms
1 2 3 4
Figure 3. Orthodromic SNAP. A. Orthodromic median nerve
sensory action potential recorded from the wrist following third digit
B stimulation. B, Relocating the active electrode slightly off the nerve
generates the same potential in A with the exception of an initial posi
tive deflection.
JSma
!IV detect the action potential's initial positivity to the same degree
and the waveform from the same nerve now appears differently,
i.e., it becomes triphasic.
In innervated muscle tissue, the above three potential mor
phologies effectively describe all waveforms likely to be encoun
tered depending on the electrode's recording location (Fig. 4).
D
Any additionally observed waveform morphologies are likely a
result of two or more single muscle fiber potentials summating
to yield a more complex appearing potential (Fig. 5A and B).4
The same three fundamental waveforms are also recorded in
neural tissue, provided comparable recordings are performed. 12
Hg 2. Endplate spike. A. Protypical end plate spikes are shown
witn a small (A-I) and relatively more prominent (A-2) so-called "pre
potential" representing the membrane approaching threshold. B.A
series of endplate spikes detected from an end plate region with slight
needle movement showing a biphasic endplate spike transition to a
triphasic end plate spike. C. Endplate spikes also may have an initial pos
itive deflection appearing as a short-duration "positive sharp wave:' D.
It is also possible to record a series of end plate spikes appearing as a
run of "positive sharp waves:' (From Dumitru D. King JC. Stegeman
OF: Endplate spike morphology:A clinical and simulation study. Arch
Phys Med Rehabil 1998;79:63+-640, with permission.)
arrived at, but did not propagate past the electrode. The quali
fiers noted in this description relate to referential recordings
with a reference (E-2) electrode far from the active source.
Exceptions to the above may result from differential amplifica
tion ofbipolarly derived action potentials (see Chapter 3). For
example, recording an orthodromic sensory nerve action poten
tial (SNAP) from the median nerve at the wrist with both the
active and reference electrodes spaced close together and
pressed firmly over the nerve, typically results in a biphasic ini figure 4. Single muscle fiber recording. A muscle fiber is de
tially negative waveform (Fig. 3A). This initial negativity arises picted with a series of recording electrodes located at the endplate
from the fact that the approaching positivity of the LD is de region and musculotendinous junction as well as several positions be
tected with relatively the same magnitude by both recordin s tween. Note that there are three primary morphologies (biphasic ini
electrodes, and is eliminated as a common mode signal. tially negative, triphasic initially positive. and biphasic initially positive)
Therefore, observing a biphasic initially negative SNAP with an that depend on the electrode's recording location with respect to the
obvious action potential propagating toward the recording elec action potential. (From Oumitru D, King JC. Stegeman OF: Endplate
trode is not a violation of the above theory. Also, if one were to spike morphology: A clinical and simulation study. Arch Phys Med
displace the active electrode slightly off the nerve in 01lr preceding Rehabil 1998;79:63+-640, with permission.)
Appendix THE LEADINGITRAILING DIPOLE MODELAND NEAR-FIELD/FAR-FIELDWAVEfORMS - 57
~
longer can be blocked by the poison tetrodotoxin. 24 The im
portant issue regarding the altered sodium channels is that
they display somewhat different kinetics and result in a less
negative resting membrane potential (closer to membrane
. + ,
~_v
. 3
threshold) and may have less effective sodium inactivation +
characteristics compared to the wild-type sodium channels.
C 0
These properties alter the initial portion of the lAP slightly in
that the rise time to peak depolarization requires just a bit ..... .....
more time than found in innervated tissue. This alteration in
time to peak depolarization, however, does not result in a dra
matic lAP alteration or its corresponding portion of the extra
cellularly recorded waveform. 3 !
On the contrary, the newly synthesized voltage-gated potas
sium channels dramatically alter the lAP's configuration, par E (+ -!C- +1 F ~-::--...:+.:.:.H+,--
fJ;' _ _ _ _ _ _ __
ticularly with respect to its terminal portion. The potassium
channels synthesized following denervation are not only volt /~
!fo -l(- +I
age-gated, but are calcium-activated and identified because of
their binding affinity to the bee venom apamin, which is not the Figure 6. Intracellular action potential. A, An lAP recorded
property of the wild types of potassium channels. 8•17,2o These from an innervated rat skeletal muscle is shown with a clear monopha
channels are referred to as SK3 (small-conductance (S) potas sic morphology. a, The lAP from a denervated rat skeletal muscle
sium (K) channels) which result in a prolonged hyperpolariza demonstrates a readily apparent hyperpolarization phase of long dura
tion of the lAP (Fig. 6A and B), It is the hyperpolarization tion resulting in a biphasic action potential. C and D, Multiplying both
phase that may contribute to the repetitive nature of sponta action potentials by a conduction velocity of 3.7 m/s generates the
neous depolarizations of the denervated muscle membrane. 24 spatial representation of the two action potentials in A and S, respec
The above description of the altered lAP can be used to better tively. E and F;The leading/trailing dipole representation of the respec
understand why fibrillation potentials and positive sharp waves tive action potentials in C and D is depicted. (From Dumitru D, King
display their respective morphologies. We may first multiply the JC, Rogers WE, Stegeman DF: Positive sharp wave and fibrillation po
lAP profile for both the innervated and denervated muscle fibers tential modeling. Muscle Nerve 1999;22:242-251, with permiSSion.)
58 - PART I FUNDAMENTAL PRINCIPLES
distance per time, or its velocity, is the first derivative of its a passive current within and across its membrane over the spec
motion. If we want to know the car's acceleration between ified crushed region. This type of membrane termination effect
points A and B, then we speak of how the velocity is changing for an lAP is called a "crushed end" or "compressed end."5
over time, Le., the car's rate of rate of change. Let us assume the We may now consider the effect a cut versus a crushed end
car traveled at a constant velocity of 60 mileslhour and, there has on an lAP when it encounters either of these termination ef
fore, its acceleration was 0 mileslhourlhour. In short, when the fects. At this point, we will consider an innervated lAP's inter
velocity is not changing, irrespective of its magnitude, or chang action with a cut and crush end to simplify the explanation and
ing only very little, the acceleration (rate of rate of change) is later consider a denervated lAP terminating at a crush region.
zero or very small, respectively. We may now apply this knowl As noted briefly above, suppose an action potential is propagat
edge to the lAP. ing toward the musculotendinous junction or, when considering
Recall that the lAP is represented in our LffD model as a nerve tissue, the terminal aspect of the nerve. A consequence of
change of voltage (increasing and decreasing) over some speci the LffD model for the transmembrane current is a triangular
fied membrane length. The rate at which this voltage changes lAP since the second derivative of a triangle just is the schema
over distance within the muscle or nerve fiber is proportional to tized double dipole used in this model. The lAP's voltage pro
the intra-axial current and may be thought of as the lAP's first file goes linearly from resting membrane potential (- 90 mV) to
derivative. 15 Second, we know that this current must exit the maximal depolarization (- + 30 to + 40 mV), and is followed by
fiber to complete the local circuit currents. The current exiting a linear repolarization back to the resting membrane level (- 90
the fiber is known as the transmembrane current or the rate at mV) (Fig. 7A). The location of the poles of the double dipole is
which the intra-axial current is changing from inside to outside indicated along the x-axis in Fig. 7A. The lAP in Fig. 7A may
the fiber, i.e., the lAP's second derivative. Therefore, how the be conceptualized as existing just prior to encountering the ab
lAP appears extracellularly depends on its transmembrane CUf sence of excitable tissue at the musculotendinous junction.
rent profile, otherwise represented as the lAP's second deriva Continued lAP propagation results in the lAP's depolarization
tive. If the transmembrane current changes significantly, a phase, and therefore the LD shortening, as there is no longer
relatively large extracellular waveform is detected. Similarly, if any tissue to sustain continued action potential propagation
the transmembrane current changes little, a negligible extracel (Fig. 7B). This process continues until the LD is completely
lular waveform is observed. gone (Fig. 7C). The TO now dissipates as its sustaining mem
It is next necessary to consider the types of action potential brane undergoes repolarization and its corresponding length de
termination that may exist. We have already addressed the most creases until it is completely gone (Fig. 7C-D). An electrode
common type of termination an action potential can encounter, located at this transition zone records a biphasic initially posi
namely the musculotendinous junction. Tendon does not pos tive potential with a terminal negative phase (Fig. 1; E-lc).
sess voltage-gated ion channels and, therefore, cannot sustain The effect a crush end has on lAP termination is quite differ
an action potential. The abrupt termination of excitable tissue in ent from that of the cut end. For our purposes, we are defining a
a complete absence of ion channels is referred to as a "cut end" crushed membrane as a region of nerve or muscle tissue with
01 "sealed end."5 On the other hand, various experiments can an intracellular space but with a complete absence of functional
II ,.; a hemostat to crush previously normal tissue, resulting in membrane voltage-gated ion channels. This means that that
the absence of voltage-gated channels but the continued pres region of crush membrane can sustain passive currents flowing
ence of a fiber with an intact interior. 9 The crushed region of across it (intracellular to extracellular) only to complete a local
fiber cannot mediate an action potential; however, it can sustain circuit current to some other region of membrane with voltage
gated ion channels. In this case, the quadrupole (+ - - +) ap
proaches a small region of crush membrane (Fig. 7E). The
A
(+
~i ___ ..)(- ~
E ~ll
0""".-""*:
---,-,(=------.. +-i
initial portion of the LD enters the crush zone because it con
sists of the initial passive current flow (Fig. 7F). Recall that only
I I I the negative sink depends on the opening of voltage-gated
I I I
I " sodium channels, while the source currents feeding the sink are
B ~n_
~ *"
F~~______::~:l
~ ~~~
primarily passive in nature and simply pass through the mem
brane to complete the local circuit current to the negative sink.
I
I
I I
I I
This process continues as the lAP propagates, with the LD
I " shrinking in size but not dissipating. The effect of a shrinking
~--- ~-. LD with continued current flow sustains a complete triangular
lAP and a balance between the LD and TO. The lAP propagates
c (+ .~ G (+ .~_: t)
I I
up to the crush zone until the portion where the open sodium
I
I
I
I
I
I
channels begin (Pig. 7G). At this point, the action potential
~: comes to a standstill. Because there is still an LD to balance the
D (+~---- H------~I+..___:.v:::....-=.;.>:;.,..~ TO, the entire quadrupole simply dissipates with repolarization
and a proportional simultaneous shrinking of the LD and TO
Figure 7. Intracellular action potential. A-D,An lAP is repre until they are both gone (Fig. 7H). An electrode positioned at
sented by the UTD model as a triangular intracellular voltage profile the crush zone's termination will detect the lAP's LD and
(cut end, see text). E-H, The region of membrane that is crushed :s record an initial positive deflection (Fig. 8C; E-1c). The magni
that portion between the vertical dashed lines. Note that this region is tude of this initially recorded positivity continues to increase
smaller than the length of the LD in this case but it may be larger as until the region of open sodium channels reaches the crush zone
well. (From Dumitru D, King JC, Rogers WE, Stegeman DF: Positive (Fig. 8C-E; E-1c). At this point, the action potential dissipates.
sharp wave and fibrillation potential modeling. Muscle Nerve Since the electrode still "sees" the LD's positivity, it records a
1999;22:242-251, with permission.) decline in the magnitude of the positive voltage (Fig. 8E; E-lc).
Appendix THE LEADINGITRAILING DIPOLE MODEL AND NEAR-FIELD/FAR-FIELDWAVEFORMS - 59
E-1A E-18 E-1C E-1D E-1E E-1A E-18 E-1C E-10 E-1E
• •
A
{-+l ~J
B
( +l J
c (+ -)e +)
F (+
-x+ -l(- +
+
~l
-.
.....
~o,.mv
""IrO
-.
-x+. . .
-)(- -H
j 1
,~------
G 1
(+ -)(+ -x -H
H
(+ "1
j 1 1
(- -I1H f-l
j 1 1
J l f f
LCl
(- +)(+ -)
K
(- <l~ oj
L
1~1
Lil
Figure 9. Single muscle fiber simulation.A schematic is shown with a recording electrode in close proximity to the fiber at the following lo
cations: fiber's origin (0 mm: E.I,J, fiber's midpoint (25 mm: E·l s), just proximal to the fiber's termination (49.75 mm: E-I d, fiber termination (50
mm: E-I D)' and just beyond the fiber's termination (50.35 mm: E-I E)' The potentials recorded from these locations are depicted to the right for the
corresponding electrode locations. A crush-type termination is modeled. (From Dumitru D, King JC, Rogers WE, Stegeman DF: Positive sharp wave
and fibrillation potential modeling. Muscle Nerve 1999;22:242-251, with permission.)
W;g' 7E-H and 9F; E-t D)' The electrode records a relatively (Fig. 9E; E-l E)' In this model, an electrode positioned directly
large positive deflection. Membrane repolarization with a corre at the crush zone termination records a rather large amplitude
sponding dissipation of the lAP's LD and TD results in a de positive sharp wave, while an electrode a few hundred microns
cline of the waveform's initial positive deflection (Fig. 9G; beyond the crush zone detects a potential with a smaller ampli
E-t D), When the lAP's leading quadrupole has completely dis tude. Therefore, the model assumes that the electrode crushes
sipated, the trailing quadrupole approaches the crush zone (Fig. the membrane a few hundred microns prior to the electrode in
9H; E-Id. The lAP's hyperpolarization phase represented by order to generate waveforms with amplitudes correlated to those
the trailing quadrupole has its LD enter the crush zone, magni clinically observed.s
fying the LD's current density. As a result, the electrode now
detects an appreciable negative voltage associated with the trail
ing quadrupole's LD negativity, thereby generating a negative NEAR·FIELD AND FAR-FIELD WAVEFORMS
spike (Fig. 91-L; E-t D)' This negative phase is of long duration
since the hyperpolarization phase lasts for such a long time. The FAR-FIELD THEORY
total waveform is identical in appearance to that of the prototyp
ical positive sharp wave. It is the combination of the lAP as con In addition to explaining near-field waveforms, the L/TD
sisting of a depolarization and hyperpolarization phase as well model also can be used to conceptualize the generation of far
as the crush zone mechanism that is proposed to account for the field potentials. In this section, the Ur'D model is used to better
formation of the positive sharp wave. The crush zone is hypoth appreciate the mator unit action potential's (MUAP) near-field
esized to occur from an adverse interaction between the muscle and far-field component waveforms. For this discussion, the
membrane and comparatively large exploring monopolar or MUAP is defined as the summated electrical activity recorded
concentric needle electrode. If there is little membrane affected, by an intramuscular electrode arising from most of the muscle
a fibrillation potential is recorded. However, if a crush type of fibers comprising a single motor unit. A motor unit consists of a
insult is produced by the electrode, the same lAP generates a single motor neuron and all of the muscle fibers it supplies.
positive sharp wave. This model successfully explains both Prior to progressing any further, it is necessary to briefly
types of waveforms (fibrillation potentials and positive sharp review a few aspects of far-field potential production. Un
waves) originating from denervated muscle tissue as derived fortunately, there is no universally accepted definition of a far
from the same lAP. An electrode located at any location distal to field potential_ Perhaps the most appropriate explanation at this
the crush zone records a waveform with the same morphology time is to simply state that a far-field potential is the waveform
as an electrode at the crush zone itself, but of a smalkr magnitude recorded at some distance from the generator source when the
Appendix THE LEADINGITRAILING DIPOLE MODEL AND NEAR-FIELD/FAR-FIELDWAVEFORMS - 61
A.
A.
+ I
I
I
+
I
I
I
I
I
I
t
I
I
B. •
I
B. I
t
+ +
c. c.
+
+
++ +
Figure I to Dipole source. A.A dipole source is depicted generat Figure 12. Dipole source. A, A dipole source is shown with its
ing both a near-field and far-field voltage distribution in an infinite cylin constituent near-field and far-field voltage distributions. B, This oppo
drical volume conductor. B. An equivalent dipolar source oriented sitely oriented dipole source is approximately half the magnitude of
opposite to that in A with its accompanying voltage profile is shown. that shown in A and may have resulted from it crossing into a larger
C. Summating the two voltage distribution of the oppositely oriented volume conductor and hence lower voltages. C, Summation of the un
dipoles generates a triphasic waveform. (From Stegeman Df, Dumitru equal voltages constituting the quadrupole action potential results in
D. KingJC. Roeleveld K: Near- and far-fields: Source characteristics and the net generation of a far-field potential because of a superimposed
the conducting medium in neurophysiology. J Clin Neurophysiol net dipole source. (From Stegeman Df, Dumitru D, King JC, Roeleveld
1997; 14:429-442, with permission.) K: Near- and far-fields: Source characteristics and the conducting
medium in neurophysiology. J Clin Neurophysiol 1997;' 4:429-442,
sources generate no far-field potentials, i.e., their identical far with permission.)
field subcomponents exactly cancel each other.
The next logical question is what happens when the LD and be considered as a balanced quadrupole before and after en
TD far-field regions do not exactly cancel each other. It is possi countering the transition region. Over this region, however, the
ble for an action potential to encounter several situations or action potential becomes a quadrupole with an imbalance be
transitions that lead to an imbalance between its LD and TD. tween its LD and TD. This implies that there is a superimposed
For example, an action potential may propagate across two non-propagating dipole source at the junction or boundary be
compartments of differing sizes (e.g., hand to finger), enter a tween the two differing volume conductor regions. In situations
region of high or low resistance within the same compartment of changing extracellular conditions (size changes, resistance
(e.g., a nerve passing through a muscle), change direction (e.g., changes), it would be wrong to state that the dipole moments of
ulnar nerve across the flexed elbow), or reach the end of ex the propagating source itself are unbalanced; rather, there is an
citable tissue (e.g., musculotendinous junction). It is the transi imbalance in the extracellular domain encountered during pas
tion between these differing circumstances that produces an sage of the dipoles. The term "virtual source" was previously
imbalance between the leading and trailing dipoles at the transi used in the main t~xt of the chapter. It is this superimposed non
tion zone. One of the dipole's (e.g., trailing dipole) may be un propagating dipole source that generates the detected far-field
changed from our previous example and display its potential and is recorded along the limb both proximal to and
subcomponent near-field and far-field voltage distributions (Fig. distal to the transition zone with an appropriate recording mon
12A). However, the leading dipole may have entered an adjoin tage. Of note, the far-field polarity will be opposite on one side
ing cylindrical compartment of larger volume with an associ of the transition region compared to the other. The best elec
ated smaller voltage for both its near-field and far-field trode montage to detect a far-field potential is to place the two
components (Fig. 12B). Summating both of these dipoles leads recording electrodes on opposite sides of the dipole source;
to a net far-field potential since the LD's far-field voltage fails however, other montages also can show far-field potentials. 9
to completely balance or cancel the TD's far-field voltage (Fig. The far-field potential will be generated for as long as the dipole
12C). There is a commensurate change in the near-field wave source is present, which in turn depends on how long it takes for
form morphology as well (Figs. IIC and 12C). The source can the action potential to completely cross the transition zone. In
Appendix THE LEADINGrrRAIUNG DIPOLE MODEL AND NEAR-FIELDfFAR-FIELDWAVEFORMS - 63
our example, as the action potential exits the finger, the LOfTD muscle's insertion reveal the anticipated triphasic waveform
balance is again established and the far-field potential dissipates appearance with a small positive potential incorporated into the
commensurate with the decline of the superimposed dipole MUAP's terminal positive phase (Fig. 14C and D). If the same
source. The above explanation applies to all muscle or nerve MUAP is recorded from different longitudinal locations along
near-field and far-field sources with an associated "ten com the muscle fiber, each further displacement from the endplate,
mandments" of far-field potential generation (Table 1). the MUAP's main negative spike becomes more delayed. This
is to be expected since it takes longer for the action potential's
MOTOR UNIT ACTION POTENTIAL negative sink to reach the electrode. However, the small positive
potential and terminal aspect of the MUAP displays a constant
We can now apply the above information regarding near-field latency (Fig. 14C and D). Similarly, the MUAP's onset also re
and far-field sources to a more accurate description of MUAPs. mains constant. It is also important to note that these MUAPs
OUf beginning point is always the lAP source for a single fiber, demonstrate a total potential duration approaching 30 ms Of
which in this case is a single muscle fiber. The traditionally used more as opposed to the anticipated lOoms MUAP duration. 2•3•6,14
lAP to model single muscle fiber potentials is that of Rosen Volume conduction models can be used to successfully simulate
falck l9•26 and is about 4-5 ms long (Fig. 13A). However, actual and explain these clinical findings (Fig. 14A and B).6,11
intracellular recordings of human skeletal muscle reveal an Let us suppose an action potential is initiated at the neuro
lAP with a very prolonged repolarization phase (greater than 20 muscular junction of a 50-mm simulated half muscle fiber (Fig.
ms) derived from the combined repolarization of the surface 15A). As previously discussed, a quadrupole develops about the
membrane and the transverse tubule system (Fig. 13B). It is neuromuscular junction with a leading dipole located to the left
possible to model this action potential (Fig. 13C) and then at and right of the neuromuscular junction. An electrode posi
tempt to explain clinical MUAP observations based on the tioned above the neuromuscular junction detects the quadru
LffO model representation of the human lAP (Fig. 130). pole's negative voltage sink, thereby recording an initial
Monopolar needle electrode recordings of MUAPs obtained negative deflection (Fig. 15A; E-IA)' The quadrupole's LD then
from the biceps brachii muscle with a reference electrode on the propagates onto the muscle membrane and subsequently a TO is
64 - PART I FUNDAMENTAL PRINCIPLES
c
~
~14,6I1V
B 0'
10ms 10ms
1 2 3 1 2 3
Figure 14. Clinically obtained and simulated MUAPs. A and B, Simulated MUAPs recorded 25 mm and 30 mm distal to a muscle fiber's
endplate region. C and 0, Clinically recorded MUAPs from the biceps brachii muscle. Vertical dashed lines I and 2 represent the onset of the near·
field and far-field potentials, respectively. The last vertical dashed line (3) signifies the potential's termination.
E-1A
, E-1S E-1C
• , , E-1A E-1S E-1C
A1:
I
+ I
I
I
I
I
I j
Otrrm 25trrrn 3()Irrrn
I I
501nTn ~~.y
~
I I I I
I I I 20...
B+:+
i
+ : I
,
I
I I '\
'"
,
I I
~
I I I
I
J
I I I
C+:+
wi
I
:-- + I
'\
• I
I
L
I
J j
I
D+~
I
:t I
l
I I
JL J
I <={+I-}=>
E+:+
I I
F ~+
, <=I+:-l=>L J J
~{J,-F> l
I
I
! J
I
G I
+I
I I
Figure'S.
H I
I
tel; & s
.c:{+I.p:..
L-J.-l
Motor unit action potentials. The LiTD model is used to explain the clinically recorded MUAPs. A 50 mm hemi-fiber muscle
length is depicted with action potential initiation at the neuromuscular junction (0 mm). Three point electrodes (E. IA, E-I B, and E·I d are posi
tioned at 0 mm, 25 mm, and 30 mm, respectively. with the recorded waveforms displayed to the right. In E-H the superimposed dipole source (+
-) is shown which generates the small-amplitude far-field potential. (From Dumitru D, King JC. Rogers WE: Motor unit action potential compo·
nents and physiologic duration. Muscle Nerve 1999;22:733-741, with permission.)
Appendix THE lEADINGfTRAILING DIPOLE MODELAND NEAR-FIELD/FAR-FIElDWAVEFORMS - 6S
generated. The recording electrode now detects the TD's posi reflects the timeframe of lAP depolarization and repolarization.
tivity and documents a positive phase (Fig. lSB; E-IA)' It is im If the above MUAPs were recorded with a concentric needle
portant to note that the lAP has a total duration approximating electrode, the terminal far-field potential component would be
30 ms because of the above-noted transverse tubular repolariza very small or simply not appreciated because both the active
tion contributing to the overall lAP duration. If we assume the (core) and reference (cannula) of the concentric electrode are
lAP is propagating at 3.7 mis, it has an overall spatial expanse located in the far-field region. 6
of about lIS mm. This means that if the muscle fiber were infi
nitely long, the entire action potential would occupy lIS mm of COMPOUND MUSCLEACTION POTENTIAL
the muscle's length. Since the muscle fiber in our simulation is
only SO mm long, by the time the lAP's LD reaches the fiber's The logical sequence of beginning with the lAP, describing
termination, the entire membrane is supporting a single action its associated extracellular waveform, and summating all the
potential (Fig. ISC-H). Therefore, the recording electrode E-I A single muscle fibers comprising a single motor unit to generate
in our example (Fig. IS) describes a potential with an initial a MUAP ends with describing the summation of all the MUAPs
negative deflection followed by a terminal positive phase. constituting a compound muscle action potential (CMAP). The
There are two additional electrodes positioned about the urn model can be used to describe both the near-field and far
fiber's middle in our example (Fig. IS; E-IB and E-ld. As the field CMAP subcomponents. We may use the prototypical
lAP's LD approaches the electrode at 2S mm (E-) B), it records CMAP recording from the abductor pollicis brevis (APB) fol
the initial positive voltage (Fig. ISB). Continued lAP propaga lowing median nerve wrist activation to begin.
tion permits the same electrode to then detect the quadrupole's In order to record the APB's CMAP, an active recording elec
negative poles while the E-Ie electrode documents the leading trode is positioned over the muscle's motor point (muscle mid
positive voltage (Fig. lSC; E-IB and E-Id. Passage of the lAP belly) with a reference electrode located on the first digit distal
then results in the E-IB electrode observing the TD's declining to the metacarpophalangeal joint. The anticipated CMAP shape
negative voltage, while the E-Ie electrode detects the quadru
pole's negative voltage (Fig. lSC; E-Id. Just before the lAP's
LD encounters the fiber's termination, these two electrodes
record a terminal positive phase of slightly different magnitude A
(Fig. ISD). So far, the electrodes record the anticipated triphasic
potential. However, when the quadrupole's LD encounters the ~2mv
musculotendinous junction, an interesting series of events
occurs.
Since there is no longer any active tissue over which the lAP
can propagate, its LD begins to collapse (Fig. 7A-D).
Dissipation of the LD creates a situation where the LD no B
longer balances the TD, resulting in the emergence of a super
imposed dipole source at the musculotendinous junction (Figs.
-mJ1mv
12C and ISE). This dipole source grows in magnitude as the im
balance between the LD and TD increases with a maximum
dipole source magnitude coincident when the LD has just com C
pletely disappeared (Fig. lSF). Because the dipole source is lo ~2mv
cated in the cylindrically shaped limb, it generates a far-field 0
potential. All three recording electrodes (E-IA' E-IB' and E-Ic)
are located in the positive region of the superimposed dipole ~2mv
source and record a positive waveform deflection (Fig. 15E-F).
The maximum positive peak of the far-field potential occurs
when the LD has just completely dissipated. Since the lAP's TD
can no longer propagate, it simply declines, which requires its
complete duration of 30 ms to accomplish. Recall that the LD E
has a duration of about 1 ms while the TD has a duration of ap .-J.mv
10.,.
proximately 30 ms. Therefore, the dipole source gradually dissi
pates with its positive pole facing the three electrodes also
slowly diminishing in magnitude (Fig. ISF-H; E-IA' E-IB' E
Ie). The net result is a waveform with an initial negative deflec Figure 16. Compound muscle action potentials. A, Biphasic
tion when recorded at the endplate but an initial positive initially negative CMAP obtained from the APB with an active elec
deflection outside of the endplate region. The portion of the trode on the muscle's motor point and a reference on the distal
waveform from initial baseline onset to initiation of the positive thumb. B, Similar recording montage as in A; however, 30 stimuli were
far-field potential represents the near-field component of the averaged and the sweep speed was slowed to 10 msldiv. C, Biphasic
single muscle fiber discharge (Fig. 14A-B). The portion of the initially negative CMAP from the ADM with a bilobed negative spike.
waveform from far-field potential onset to waveform termina D, Relocating the active electrode from the ADM to the lateral epi
tion signifies the waveform's far-field potential component (Fig. condyle reveals a quadraphasic initially negative far-field potential. E,
14A-B). Summating the electrical potentials of all the single Same recording as that in C, but with a sweep speed of 10 ms/div.
muscle fibers comprising a motor unit generates the MUAP Note: N I and N2 refer to the first and second negative peaks while
with its near-field and far-field subcomponents (Fig. 14C and P 1-P2 refer to the first through second positive peaks. The designation
D). Since the total lAP is about 30 ms, the total MUAP duration "F" demarcates the CMAP's associated F-wave.
66 - PART I FUNDAMENTAL PRINCIPLES
!~J
2
A
B
_ •.
11
J
y
,....
t=J. tion between the terminal positive repoiarization phase for the
waveform and the initiation of the far-field potential. With a
short fiber length (Fig. 17A; # I and #2), the action potential en
counters the fiber's termination shortly after forming the wave
e
!\r-
t=
form's negative spike with a subsequent fusion of the fi~r's
0
E
u
~
'--
~\-
(Figs. 16A and 17 A). Therefore, the terminal positive phase
i
'v+--- (Fig. 16A; PI) for the APB CMAP represents some portion of
~L
F
G :/~
JL the anticipated membrane repolarization as well as the sum
mated far-field potentials of all the APB's fibers encountering
:/
I;
j
_.~,/
Jl(M / ~/
the musculotendinous junction because of the short fiber length.
Altering the sweep speed for the APB recording from 3
H
/1 i /B;;a
L----L~ ~ litV
,I '
/ /'
ms/div to 10 ms/div reveals that the CMAP's termination re
quires approximately 62 ms with respect to the waveform's
l l /~ 8 -Jl~~%?
onset (Fig. 16B). Again, this finding can be explained by con
/ sidering the single muscle fiber LlTD explanation (Fig. 15).
J
K
f L "8
~'--/ jlL;;? Recall that the waveform's long terminal phase arises from the
action potential's long repolarization phase that only becomes
~
L
~
~-'/'
i;;:::=1
:/E
-J\-L;;?
fl :/8
manifest during the formation of a quadrupole imbalance. This
same situation applies to the CMAP's summated action poten
tials. However, instead of the 30-ms duration, the CMAP has a
"
L----+./'~-
,
------J b, / / terminal phase approximately twice that long. This can be ex
M
~
'l----
!/S
~ // -
-Jl ''/9
" //'
plained by considering that there is in effect a double discharge
occurring in the muscle following median nerve wrist activa
tion. The fibers are all excited initially by the neural stimulus,
Figure 17. Single muscle fiber simulations. A series of 13 single and then a small percentage of fibers are secondarily activated
muscle fiber lengths (10-130 mm) are shown inA-M with a recording (F-wave, Fig. 16B; "F"). Combining the far-field potentials
electrode positioned at the muscle's endplate (column I) and midway from both activations and averaging a number of responses per
between the endplate and musculotendinous junction (column 2) with mits detection of the CMAP's far-field potential and its associ
a reference at infinity. Note how the far-field potential (small positive ated long return to baseline.
peak) is merged with the short fiber length (10 mm) and is progres The CMAP derived from the abductor digiti minimi (ADM)
sively displaced from it as the muscle fiber length increases from 10 and other hypothenar muscles following ulnar nerve stimulation
mm to 130 mm for both electrode locations. (From Dumitru D. King usually demonstrates an initially negative biphasic CMAP;
JC: Motor unit potential duration and muscle length. Muscle Nerve however, the negative spike is typically bi-Iobed or has a notice
1999;22:1188-1195, with permission.) able "hump" in its rising phase (Fig. 16C). This waveform's
morphology has been attributed to the active recording elec
conforms to that of a biphasic initially negative potential (Fig. trode positioned over several muscles in the hypothenar emi
16A). This waveform morphology is essentially the same as that nence yielding two negative peaks. However, a similar shape is
previously described for an electrode located over the muscle's not seen for the APB's CMAP, which also arises from several
endplate region (Fig. 15; E-l A)' It is important at this juncture to muscles. Relocating the active electrode from the abductor
point out the differences between endplate recordings per ADM motor point to the lateral epicondyle reveals primarily a
formed for the single muscle fiber in Figure 15 and the CMAP triphasic initially positive waveform (Fig. 16D). Since the active
from the APB (Fig. 16A). The single muscle fiber waveform re electrode is on the lateral epicondyle and the reference electrode
veals a distinct positive far-field potential with respect to the ini on the distal fifth digit, the observed waveform must be a far
tially negative near-field waveform originating from the field potential. Investigations have concluded that the CMAP's
endplate. However, the APB waveform similarly has the ini second negative peak is derived from the medial interos
tially negative onset, but a negative spike that seamlessJy blends seousllumbrical muscle's action potentials dissipating at their
into a terminal positive phase (Fig. 16A; Nl-Pl). This discrep respective musculotendinous junctions forming far-field poten
ancy can be understood if one considers the effect of different tials that coincide with the ADM's near-field waveforms. IO• 13
fiber lengths on the ensuing waveform morphology. Let us con The net result is a CMAP with a bi-Iobed negative spike par
struct a series of single muscle fibers ranging in length from 10 tially derived from the hypothenar muscles' near field (Fig.
mm to 130 mm (Fig. 17). We can then place a recording elec 16C; Nt) and interosseousllumbrical muscles' far-field compo
trode at the muscle fiber's endplate (Fig. 17A-M; #1) and nents (Fig. 16C; N2). This waveform's terminal positive phase
halfway between the endplate and the fiber's musculotendinous is likely derived from the same mechanism generating the
junction (Fig. 17A-M; #2) for each fiber length. The far-field APB's terminal positive phase, i.e., dissipation of the ADM's
potential demonstrates the same duration for each fiber length action potentials at its musculotendinous junctions. Finally, al
since it depends on the lAP shape beginning when the action tering the sweep speed of the ADM recording also reveals a
potential encounters the musculotendinous junction. If the fiber long terminal positive phase duration approaching 60 ms (Fig.
is long, it will take a relatively long time before the action po 16E; "F") with an explanation similar to that previously given
tential initiated at the endplate terminates at the musculotendinous for the APB.
Appendix THE LEADINGfTRAILlNG DIPOLE MODEL AND NEAR-FIELD/FAR-FIELDWAVEFORMS - 67
The above discussion clearly shows that the intuitive notion 7. Dumitru D, King IC: Motor unit potential duration and muscle lengtb. Muscle
Nerve 1999;22:1188-1195.
of recording the CMAP from the ADM when the active (El) 8. Hugues M, Schmid H, Romey G, et al: The Ca2+-dependent slow K+ conduc
electrode is placed over the hypothenar eminence is a miscon tance in cultured rat muscle cells: Characterization with apamin. EMBO J
ception. The recorded CMAP is a complex mixture of both 1982;1:1039-1042.
near- and far-field contributions from all ulnar-innervated hand 9. Jewett DL, Deupree DL: Far-field potentials recorded from action potentials and
from a tripole in a hemicylindrical volume. Electroencephalogr Clin Neuro
muscles. Depending on the number and configuration of mus physioI1989;72:439-449.
cles innervated by a particular nerve the CMAP can have differ 10. Kincaid IC, Brasher A, Markand ON: The influence of tbe reference electrode on
ent forms and distribution. This was shown by recording CMAP configuration. Muscle Nerve 1993;16:392-396.
II. Lateva ZC, McGill KC: The physiological origin of the slow afterwave in
CMAP's at mUltiple electrode positions over the hand and foot muscle action potentials. Electroencepha!ogr Clin Neurophysiol 1998; I 09:462
area and stimulating the ulnar, median, peroneal, and tibial 469.
nerve resulting in CMAP cartography. The distribution of an 12. Lorente de No' R: A study of nerve physiology. Studies of tbe Rockefeller
area of a high and well-defined negative peak was remarkably Institute for Medical Research 1947;132:384--482.
13. McGill KC, Lateva L£: The contribution of tbe interosseous muscles to tbe hy
different for the studied nerves, being small for the median and pothenar compound muscle action potential. Muscle Nerve 1999;22:6-15.
peroneal and large for the tibial and ulnar nerves. 25 14. Nandedkar SD, Dumitru D, King JC: Concentric needle electrode duration mea
surements and uptake area. Muscle Nerve 1997;20:1225-1228.
15. Noble D: Application of Hodgkin-Huxley equations to excitable tissues. Physiol
Rev 1966;46:1-50.
CONCLUSION 16. Nunez PL: Electric Fields of tbe Brain: The Neurophysiology of EEG. New
York, Oxford University Press. 1981;82--83.
The leading/trailing dipole model can be used to described a 17. Prinbow D. Iohnson-Pais T, Bond cr, et al: Skeletal muscle and smail-conduc
tance calcium-activated potassium channels. Muscle Nerve 1999;22:742-750.
number of near-field and far-field waveforms observed during 18. Purves D, Sakman D: Membrane properties underlying spontaneous activity of
the routine electrodiagnostic medicine examination. The above denervated muscle fibers. J PhysioI1974;239:125-153.
defined principles can be applied to situations not detailed in 19. Rosenfalck P: Intra- and extracellular potential fields of active nerve aod muscle
fibers. A physico-matbematical analysis of different models. Acta Physiol Scand
this discussion to explore new aspects of near-field and far-field 1969;(Suppl 321):1-168.
sources in biologic systems. The interested reader is encouraged 20. Schmid-Antomarchi H, Renaud J, Romey G, et al: The all-or-none role of inner·
to apply the simple quadrupole model when familiar or even vation in expression of apamin receptor and of apamin-sensitive Ca2+-activated
K+ channels in mammalian skeletal muscle. Proc Natl Acad Sci USA 1985;
new waveforms are observed. 82:2188-2191.
21. Stegeman DF, Dumitru D, King IC, Roeleveld K: Near and far fields: Source
characteristics and the conducting medium in neurophysiology. I Clin
REFERENCES Neurophysioll997; 14:429-442.
22. Thesleff S: Physiologic effects of denervation on muscle. Ann N Y Acad Sci
l. Dumitru D, Jewett DL: Far-field potentials. Muscle Nerve 1993;16:237-254. 1974;228:89-103.
2. Dumitru D, King JC, Nandedkar SD: Motor unit action potential duration 23. Thesleff S, Ward MR: Studies on tbe mechanism of fibrillation potentials in den
recorded by monopolar and concentric needle electrodes: Physiologic implica ervated muscle. J PhysioI1975;244:313-323.
tions. Am I Phys Med Rehabil 1997;76:488-493. 24. Thesleff S: Fibrillation in denervated mammalian muscle. In Culp WJ, Ochoa J
3. Dumitru D. King IC. Nandedkar SD: Motor unit action potentials recorded ",itb (eds): Abnormal Nerves and Muscle Generators. New York, Oxford University
concentric electrodes: physiologic implications. Electroencephalogr Clin Neuro Press, 1982, pp 678-694.
physioll997;105:333-339. 25. Van Dijk JG, van Benten I, Kramer CG. Stegeman DF: CMAP amplitude cartog
4. Dumitru D, King IC, Stegeman DF: Endplate spike morphology: A clinical and raphy of muscles innervated by tbe median, ulnar, peroneal, and tibial nerves.
simulation study. Arch Phys Med Rehabill99B;79:634-640. Muscle Nerve 1999;22:378-389.
5. Dumitru D, King IC, Rogers WE, Stegeman DF: Positive sharp wave and fibril 26. Van Veen BK, Wolters H, Wallinga W, et aI: The bioelectric source in computing
lation potential modeling. Muscle Nerve 1999;22:242-251. single muscle fiber action potentials. Biophys I 1993;64: 1492-1498.
6. Dumitru D, King IC, Rogers WE: Motor unit action potential components and 27. Wiechers DO: Electromyographic insertional activity in normal limb muscles.
physiologic duration. Muscle Nerve 1999;22:733-741. Arch Phys Med RehabilI979;60:359-363.
Chapter 3
Instrumentation
CHAPTER OUTI_INE
Stimulators
Amplification • Input Impedance
Performing an electrodiagnostic medicine consultation re number of signal acquisitions to make it more distinct from
quires a thorough understanding of how the electrophysiologic random background noise, i.e., average a number of trials and
instrument processes and displays biologic signals. This knowl improve the signal-to-noise ratio. Visual and acoustic informa
edge will help the practitioner avoid misinterpreting erro tion required to diagnose potential pathology can be gathered as
neously derived data due to instrumentation errors as possible it occurs spontaneously from voluntary activity or evoked
pathology. The basic principles covered in this chapter are through a time-locked depolarizing stimulus delivered from the
shared by the majority of instruments likely to be used. instrument's stimulator. The most important aspect to remember
Recording electrodes located in or on the patient detect the rela regarding instrumentation is that the skills necessary to practice
tively small voltage changes associated with a nerve or muscle electrodiagnostic medicine ultimately depend on the practi
action potential and convey them to an amplifier (Fig. 3-1). tioner and not the instrument irrespective of its sophistication.
Following amplification, the signal is filtered to remove any ex
traneous electrical activity that may distort the waveform under
investigation. The real-time (analog) information can then be BASIC ELECTRONIC CIRCUIT PRINCIPLES
presented acoustically and visually. The signal is usually con
nected to an audio speaker so that the sound associated with an ELECTRONIC CIRCUITS (OHM'S LAW)
action potential can be appreciated. The analog data can also be
presented visually in one or both of the following formats. An Only a basic understanding of electronic circuitry is required
analog waveform can be displayed on a cathode ray tube (CRT) to adequately appreciate the electrophysiologic instrument's
for immediate visual inspection, or with a minimal delay trans function and effect on biologic signals. We can begin with a
formed into a binary (digital) signal through an analog-to-dig simple circuit containing a battery (E) (voltage/current source)
ital (AID) converter and then displayed (Fig. 3-1). Once the connected to a resistor through wires (Fig. 3-2A). The battery is
waveform is digitized, it is possible to store and summate a symbolized by a series of short and long horizontal lines. The
69
70 - PART I FUNDAMENTAL PRINCIPLES
Fillers (C) circuit or to each of its parts. A unit of resistance is the ohm and
~~~I~f.i~~ ~~!: CRT (E) is defined as: I ohm = I voltll ampere. IS A symbol for ohm is
.------+-!,~+ ' the Greek letter omega (Q). If two resistors are placed sequen
tially in the above circuit, they are said to be in series. The cur
o---::r--r-o
~ rent passing through each resistor is the same, but the battery's
source voltage is equal to the sum of the voltage drops across
Active each resistor (Fig. 3-2B). The total voltage of the circuit is equal
Palienl(A) to the sum of the voltages across each resistor in the circuit:
Etotal = EI + E2 and substituting the current and resistance for
each resistor component in the circuit results in Etotal = IRI +
IR 2. By factoring out the constant current term, resistances in
series can be summated: Etotal = I(R I + R2). A circuit with sev
Figure 3-1. Schematic representation of the electrophysio eral resistors in series, therefore, may act as a voltage divider
logic instrument's component parts, Electrodes in or on the pa in that the total voltage drop across all of the resistors consists
tient (A) detect action potentials and transmit them to a differential of the sum of the voltage dropping across each resistor (Etotal =
amplifier (B). The differential signal is filtered (C) and then fed to both El + E2 +...+ En)·
the loudspeaker (F) for aural analysis as well as to the analog-to-digital In addition to a resistor, one can also place a capacitor in a
converter (D) for a digital representation of the analog signal. The circuit (Fig. 3-2C). A capacitor is a device that stores charge.
signal is then ready for visual display on the cathode ray tube (E). Typically, a capacitor consists of a pair of parallel metal plates
Excitation of the peripheral nervous system is possible with the stimu separated by an insulator, i.e., a material that conducts current
lator (G). (From Dumitru D,Walsh NE: Electrophysiologic instrumen poorly.IS The insulator, also called a dielectric, may be air, oil,
tation. In Dumitru D (ed): Clinical Neurophysiology. Philadelphia, glass, wax paper, or some other poorly conducting material. The
Hanley & Belfus, 1989, with permission.) capacitor's capacitance (C) is the property that determines its
ability to accumulate charge and is defined as the ratio of the
charge on either plate to the potential difference across both
short line is the negative terminal while the long line is the pos plates. If an open switch is placed in the circuit, an open circuit
itive terminal. A resistor (R) is a relatively poor conductor that exists and current will not flow. When the switch is first closed,
offers a quantifiable hindrance to the flow of charge and is sym the circuit is completed and current flows from the positive bat
bolized by a jagged line in circuit diagrams (Fig. 3-2).IS The tery terminal to the capacitor plate to which it is connected. This
flow of unit charge per unit time is called current (I). It is as plate then accumulates a positive charge until the voltage across
sumed that the wires connecting the resistor and battery offer the capacitor plate is equal to the potential of the battery. A sim
minimal opposition to current flow. By convention, current ilar process occurs at the capacitor's plate connected to the neg
flows from the positive to negative battery terminal across the ative battery terminal except that the charges are negative.
resistor, whereas in metallic circuits electrons travel in the op During the charging process, although current did not actually
po"ite direction. If one measures the current passing through the cross the capacitor, a potential across the capacitor developed in
resistor when the voltage applied across the resistor is changed, that positive charges accumulated on one plate and were re
the current is found to be directly proportional to the applied moved (accumulation of negative charges) from the other plate.
voltage. This qualitative statement may be expressed quantita As it takes a finite time to charge the capacitor, current only
tively by a mathematical expression. The current (I) is equal to flows during this charging process. If the switch is again
the voltage (E) times a constant (g) called conductance that is a opened, the capacitor will hold its charge until it is discharged
property of the resistor: I = g x E. It is more common, however, by some external process where the plates are connected by
to use the inverse of the conductance (lIg) i.e., the resistance some form of electrical conductor, e.g., a wire.
(R) of the resistor (R = lIg). The mathematical expression I = g
x E then becomes: I = EIR or E = I x R (Ohm's law). A restate ALTERNATING CURRENT (AC) CIRCUITS
ment of the mathematics is that the current in a circuit is directly
proportional to the voltage applied to the circuit and inversely In the above discussion, Ohm's law is described for circuits
proportional to the circuit's resistance (I = EIR). This relation in which the applied voltage remains constant. In biologic sys
ship is named for Georg Ohm and may be applied to an entire tems, however, the signals of interest may have a fluctuating or
alternating voltage or current source. Consideration of alternat
ing current circuits gives one a more realistic appreciation of
A B c events associated with biologic current flows, i.e., action poten
tials. If a circuit orly contains a resistive component, Ohm's law
can be used with minimal modification. In an AC circuit, the
hindrance a circuit element provides to AC current is no longer
called resistance (R) but impedance (Z).IS.S3 A capacitor, how
ever, behaves somewhat differently than a resistor in an alternat
ing circuit. The alternating current generator (counterpart to the
Figure 3-2. Simple circuit diagrams. A, The current source (bat DC circuit's battery) causes electrons to surge back and forth
tery) generates a voltage difference that drops across the resistor. through the generator to one capacitor plate and then the other,
=
Recall Ohm's law for a direct (E I x R) and alternating (E I x Z) = i.e., charge/discharge. During the charging phase, like charges
current. B,An additional resistor has been placed in the circuit and a accumulate on the capacitor's plates that tend to repel continued
voltage drop occurs across each resistor forming a voltage divider. C, charge addition. As a result, the current in the circuit is some
One of the resistors in B has been replaced with a capacitor. what smaller than it might be if the capacitor were not present.
Chapter 1 INSTRUMENTATION - 71
A B c D
e e e e .... e e ...
e ... e ...... et&+
e e e e ..... e e <IIIHI.
e .. e • e e ....
e e e e ..... e e ••
e .... e • e e ... .
e • e e .... e e ... .
e ... e ... e ..
e CIt e e ... e e e ....
Figure 3-3. Formation of an electrode potential. A, Ions flow from the electrode into the electrolyte solution. B,The ions accumulate in the
electrolyte solution and an uneven charge distribution develops. C,lons flow from the metal surface into solution and from the solution back into
the metal at unequal rates. D.A situation develops at some time where an ionic equilibrium may not be present. Movement of the electrode will
cause this voltage difference to discharge possibly interfering with recording of the potential under investigation. (From Cooper R: Electrodes.Am J
EEGTech 1963;3:91-101, with permission.)
The opposition a capacitor has to an alternating current is called hindrance (impedance) to the energy contained within a wave
its capacitive reactance (Xc) and for our purposes represents form. The skin/electrode interface may have an impedance
the capacitor's impedance (Z). The capacitive reactance's units ranging from 500 0 to 9 MO (M: mega or million) depending
are ohms and its magnitude is expressed mathematically as : Xc upon the measurement location. 39,54 One way to improve the
= 1I(21tfC) =Z. Although this formula looks imposing, there are signal's amplitude is to apply an electrolyte cream between the
two simple concepts to remember. First, as the capacitance (C) recording electrode and skin's surface stratum corneum layer.
increases, the reactance or impedance to current flow decreases, The ions within the electrolyte improve the transmission of
i.e., mathematically the denominator increases in magnitude, biologic signals through the skin to the electrode's metal sur
therefore the net result or impedance must decrease. Second, the face. With time, however, a chemical reaction occurs at the elec
capacitive reactance (Xc) is frequency (f)-dependent. In a direct trolyte/electrode interface and a voltage difference or electrode
current (DC) circuit, the frequency of the current is zero and the bias potential can be produced. 14 The electrode potential is be
reactance becomes infinite, implying that a constant (DC) cur lieved to arise from two opposing processes: metallic ions pass
rent will not flow across the capacitor in the steady state. This ing from the electrode into solution, and the subsequent
suggests that low frequencies have difficulty crossing a capaci deposition of metallic ions back onto the electrode (Fig. 3-3).
tor. On the other hand, high frequencies reduce the capacitive The rates of these two ionic movements are not necessarily
reactance so that little opposition to current flow is present, al equal and if there are more ions leaving the metal than return
lowing these frequencies of current to pass without diffi ing, an excess of positive ions will be in solution compared to
culty.15,53 Magnetic fields induced by alternating current flow the electrode's surface. This charge separation generates the
also oppose the current emanating from the generator. For prac electrode bias potential. Slight movement of the electrode can
tical purposes, this inductive reactance can usually be ignored cause this voltage to suddenly discharge and disturb the wave
in the human body.47 The opposition to an alternating current, forms under investigation. A special cup-shaped electrode
therefore, is called impedance (Z) and composed of the resis design can minimize this possible discharge voltage artifact (see
tive and capacitive elements in a circuit. Ohm's law can be ap below).
plied to biologic systems using impedance and is usually A second way to reduce the skin's impedance is to gently
written as: E = I x Z. remove several layers of the stratum corneum by mild abrasion
with a pumice solution or fine sandpaper. The smaller the po
tential to be recorded, the more important it becomes to reduce
ELECTRODES the skin's impedance. When performing routine nerve conduc
tion studies, it is rarely necessary to aggressively abrade the
SURFACE ELECTRODES skin. The amplitude of somatosensory evoked potentials, how
ever, may be less than a microvolt and require the skin's imped
The action potential's magnitude generated by different ex ance to be reduced below 5,000 0. 48
citable tissues in the body may vary between several tenths of a
microvolt (J.lV) to possibly 50 millivolts (mV).34 In order for Electrode Types
these signals to be analyzed, they must be recorded with an Surface electrodes are used to evaluate sensory nerve and
electrode. This electrode can be located on the skin surface or motor muscle compound action potentials, somatosensory
inserted through the skin and placed in close proximity to either evoked peripheral and cortical potentials, and occasionally sum
the nerve or muscle generator. As surface electrodes are used mated motor unit action potential activity. Because different
for many recording purposes, we must consider one of the recordings are made from various regions of the body, a large
major partitions between the action potential and recording variety of electrodes are necessary, e.g., discs, disc electrodes
electrode, i.e., the skin. Although the skin performs vitally im embedded in a plastic bar, self-retaining clips, adjustable wire
portant biologic functions, it does have a tendency to reduce the nooses, or saline-soaked felt pads. Aside from the saline pads,
amplitude of the potentials under investigation when surface most electrodes are made from a metal that readily conducts
electrodes are used. The potential's magnitude is diminished for current (e.g., silver, gold, tin, stainless steel, platinum, lead, or
surface recordings because the skin offers a certain amount of nichrome).
72 - PART I FUNDAMENTAL PRINCIPLES
A commonly used surface electrode is a flat or cup-shaped amplitudes also applies for these self-adhesive electrodes. A
disc with a diameter ranging from 0.5 to 2.5 cm. The electrode single study has found that for a limited number of examined
that is cup-shaped or one with a small depression in its center motor and sensory studies, the potentials latencies were equiva
may obtain recordings with less artifact than simply a flat sur lent for the standard stainless steel electrodes and self-adhesive
face. This is because the electrode's central depression can be types. 3 Aside from the above-noted amplitude differences with
filled with the electrolyte and any movement between the skin respect to size, all amplitude measurements were still well
and electrode occurs at the skin/electrolyte interface away from within reference values irrespective of the electrode type used.
the recessed electrolyte/electrode interface. 14•34 Because move It is still a good practice to establish one's own reference popu
ment occurs away from the region of the electrolyte/electrode lation when using a new type of electrode.
interface, there is less likelihood of discharging the electrode
bias potential. Electrical Continuity
Aside from the self-retaining electrodes, adhesive tape is After appropriate electrodes have been chosen, a good prac
commonly used to secure the recording electrodes to the skin. tice is to routinely assess their inherent electrical continuity and
Collodion, a quick-drying liquid adhesive may be used in the the electrode/skin contact. It is necessary to check the electrical
recording of evoked potentials. 48 Although this is a relatively integrity of recording electrodes because the wires underneath
common practice, it is potentially untidy, gives off malodorous the intact plastic coating can unknowingly break. The recording
fumes, requires a drying apparatus, and is somewhat time-con electrode's resistance is measured with an ohmmeter. The ohm
suming. Securing electrodes with Collodion offers the advan meter passes a direct current through the wire and measures the
tage of stable and relatively artifact-free recordings that can be resistance. 15 Intact electrode leads should have a resistance less
performed over a prolonged period. An alternative to Collodion than several thousand ohms.48 If the resistance is noted to be
for the recording of evoked potentials is a thick and sticky elec greater than this value, a faulty lead is likely present and the
trolyte cream applied to the electrode, which is then covered electrode should be discarded.
with cotton and tape to maintain the electrodes' position. When the electrode is secured to the skin's surface, the elec
An important aspect of the electrode is also the cable con trical continuity between the skin and electrode can be assessed
necting the electrodes to the amplifier. This is often a source of by measuring the impedance. Most modern instruments have
artifacts by picking up electromagnetic radiation from the envi built-in impedance meters that allow the practitioner to easily
ronment. It can be circumvented by not using unnecessarily determine the impedance by passing a weak alternating current
long cables of equal length. The use of twisted cables can of a fixed frequency through the electrodes. 48 The alternating
promote the pickup of similar amounts of electromagnetic radi current is chosen because it is more representative of a time
ation which by way of the common mode rejection (see varying biologic signal. Additionally, alternating current limits
Amplifiers) will be adequately suppressed. It is also important the polarizing effect a direct current may have on the electrodes.
to arrange the wires in such a way that cables from the stimula As previously stated, it is common practice to record the imped
tor and recording part of the equipment are neatly separated and ance when performing evoked potentials. One prefers to keep
do not cross. the impedance between 1,000 nand 5,000 n for evoked poten
tial studies. 48 If an impedance less than 1,000 n is observed, it
Electrode Size is possible that an undesired conduction pathway such as excess
An important but all too infrequently discussed aspect of electrolyte gel on the skin's surface or perspiration linking both
recording surface action potentials, in particular CMAPs, is the electrodes is present. An impedance greater than 5,000 n for
effect electrode size has on the potential. There can be consider surface electrodes can attenuate the signal. Impedances signifi
able inter-trial variation on CMAP parameters27 and certainly cantly larger than 5,000 n despite adequate skin preparation
one contributing factor is electrode size. 2 ,56,57,59 In general, larger may suggest a loose electrode/skin contact or broken lead wire.
compared to smaller recording electrodes result in CMAPs with It is important that both electrodes have a similar impedance
slightly smaller amplitUdes and area and slower conduction ve when in contact with the skin otherwise an impedance mis
locities, but no clinically significant difference regarding onset match can reduce common mode rejection (see Amplifiers) and
latency or negative spike duration. This is understandable if one increase 60-cycle interference, adversely affecting the desired
considers the fact that a larger electrode will obviously record signal.
from a larger region of the volume conductor, thus averaging
out the different contributions from individual motor units. Electrode Separation
Further, the summated electrical activity from a muscle will be Surface electrodes are usually placed in specific locations to
"averaged out" over a larger piece of metal, thereby decreasing optimize waveform recordings. In assessing compound muscle
the overall CMAP's amplitude compared to a smaller electrode action potentials (CMAPs), the active or E-I electrode is
size. It has been shown for CMAP amplitudes that larger elec placed on the mu;;cle's motor point and the reference or E-2
trode size results in lower CMAP amplitudes and reduced vari electrode is located in an electrically inactive region (see
ability; however, the effects on possible diagnostic utility is Chapter 2). This electrode montage will maximize the poten
unknown. 57 At present, there remains a lack of uniformity of tial's magnitude as it minimizes common mode signals from
opinion and hence practices regarding the preferred size for sur being recorded (see Amplifiers). The effect various electrode
face electrodes. locations have on CMAPs can be readily demonstrated (Figs.
Manufacturers have introduced self-adhesive silver-silver 3-4A and B). When the E-I electrode is placed over the
chloride (Ag/AgCI) electrodes for nerve conduction studies muscle's motor point and E-2 distally away from activated
similar to those used for years in the electrocardiology (EKG) muscle tissue, a large biphasic CMAP is recorded. Relocating
laboratory. These electrodes are quite flexible and can be easily the E-2 electrode onto the same muscle as E-l results in a
altered in shape by cutting them to fit any desired region. The marked CMAP amplitude reduction, minimal peak latency
above general principles of larger electrodes yielding smaller shortening, but no effect on the onset latency.
Chapter] INSTRUMENTATION - 73
~----- 4.0 cm may result in similar signals being recorded from both
electrodes, resulting in an amplitude reduction. This finding is
easily demonstrated by evoking an antidromic SNAP and se
quentially increasing the interelectrode separation in l.O-em in
Amplitude crements (Fig. 3-SA).IS Changing the interelectrode distance
Latency Peak from 1.0 to 4.0 cm does not alter the onset latency but increases
Trace Baseline
onset to the peak latency by 10% while the amplitude increases 53%.
to peak The SNAP's onset latency does not change because the active
peak
electrode did not change and, therefore, the distance between
ms mV the site of neural activation and the E-I electrode remained con
A 3.5 11 21 stant. The SNAP's amplitude increases because the reference
B 3.5 5 9 electrode records less of what the active electrode detects. i.e.,
the SNAPs rising negative phase. Since less similar information
Figure 3-4. Effect of interelectrode separation on the ampli is recorded, less of the same information is eliminated by the
tude of the compound muscle action potential (CHAP). A, differential amplifiers resulting in a larger potential. Similarly,
CMAP detected from the thenar muscles following median nerve acti the peak latency increases in latency since the SNAP's peak is
vation: E-I on the muscle's motor point and E-2 at a distant location permitted more time to develop since less of it is eliminated as a
away from activated muscle tissue. B. CMAP observed when E-2 is lo common mode signal (see Amplifiers). Beyond 4.0 cm of elec
cated on the thenar muscles near E-I. Note the reduction in ampli trode separation these waveform parameters change minimally.
rude. (From Dumitru D,Walsh NE: Electrophysiologic instrumentation. Therefore, electrodes that are too close together shorten the
In Dumitru 0 (ed): Clinical Neurophysiology. Philadelphia, Hanley & peak latency and reduce the amplitude, but do not affect the
Belfus. 1989, with permission.) onset latency. A slower maximal fiber conduction velocity
allows one to place the electrodes closer together without com
promising the amplitude. The same principle applies to ortho
dromic recording techniques.
It can be appreciated from the above examples that proper
electrode placement is crucial to accurately record waveforms.
Errors usually result when the electrodes are too close together.
A reduction in amplitude may cause one to inappropriately
assume that some form of pathology has resulted in the loss of
excitable tissues when in fact this observation is an artifact re
sulting from too short an interelectrode separation. It is also
possible to record too short a peak latency when there may be
actual prolongation. This misreading of latency can result in an
artifactually normal result and thus true pathology may be
missed.
NEEDLE ELECTRODES
Latency Electrode Types/Impedance
Interelectrode
Trace Amplitude Needle electrodes are usually chosen so as to approach the
distance Onset Peak bioelectric signal's generator source. Near-nerve needle elec
em ms i-I V trodes can be used to record from or stimulate single peripheral
nerves (see Chapter 2). Intramuscular electrodes are used to
A 1.0 2.7 3.0 56
record single-muscle-fiber waveforms or the summated electri
B 2.0 2.7 3.1 72
cal activity of multiple muscle fibers forming the motor unit
C 3.0 2.7 3.3 77 action potential (MUAP). Subdermal electrodes also are avail
D 4.0 2.7 3.3 86 able to record somatosensory, auditory, and visual evoked po
E 5.0 2.7 3.3 86 tentials. The following are commonly used in clinical practice:
monopolar needles, standard concentric needles, single-fiber
Figure 3.5. The effect of varying Interelectrode separation needles, and subdermal electroencephalographic needles.
on an antidromic median nerve SNAP. Sequentially increasing The use of a needle electrode implies that it is placed into the
the electrode separation from 1.0 cm to 5.0 cm produces the body's volume conductor and is in contact with the extracellular
above-detailed latency and amplitude changes. (From Dumitru 0, fluid, an electrolytic solution. A chemical reaction between the
Walsh NE: Electrophysiologic instrumentation. In Dumitru 0 (ed): electrode's metal surface and the surrounding electrolytic solu
Clinical Neurophysiology. Philadelphia, Hanley & Belfus. 1989. with tion can occur for needle electrodes just as it does for the sur
perm ission.) face electrode/electrolyte cream interface. The needle electrode,
74 - PART I FUNDAMENTAL PRINCIPLES
similar to the surface electrode, has the property of impedance detected in the uptake area. Compared to standard concentric
consisting of resistance, capacitive reactance, and inductance needle electrodes, monopolar needle MUAP recordings have
(usually negligible). As expected, the capacitive reactance is in been reported to yield somewhat longer durations and larger
versely proportional to the signal's frequency content amplitudes. 12 Studies demonstrated up to 40% of normal
Monopolar Needle Electrode. The monopolar needle was MUAPs (depending upon the muscle) recorded with a monopo
first used in electromyographic (EMG) analysis by Jasper and lar needle are polyphasic versus 3-20% for standard concet:ltric
Ballem. 31 A monopolar needle is made of solid stainless steel needle electrodes.6.7.10.29.55 Additional investigations have found
12-75 mm in length and 0.3-0.5 mm in diameter. The entire that although monopolar needle recordings yielded significantly
needle is sheathed in Teflon except of the distal tip, which is higher amplitudes and more polyphasic MUAPs compared to
bare metal for 25-50 /Jll1 or more. 10. II The actual recording sur concentric needle recordings, the MUAP's duration for both
face is cone-shaped with a sharp tip and an area approximately needles were not significantly different. 3O.43 The disparate
0.17 mm2 • The monopolar electrode is less expensive and gen MUAP duration findings of various studies may stem from how
erally better tolerated by the patient but less durable than the the MUAPs were recorded with respect to the rise time, i.e.,
concentric needle electrode (see below).51.53 However, today's recording methodologies. Maximizing amplitude and minimiz
manufacturing techniques permit disposable monopolar elec ing rise time « 500 115) suggests that one is very close to a
trodes to have good recording characteristics for one-time use. select population of muscle fibers. Ignoring these parameters
Monopolar needle electrodes produce relatively little patient would yield potentially different results with respect to total
discomfort because the sharp pointed tip pierces the skin easily MUAP amplitude and possibly duration. At the present time,
and the shaft's Teflon coating glides readily through muscle commercially available monopolar needles appear to give
tissue. With repeated use of the electrode, the Teflon may peel MUAPs with larger amplitudes. more phases and turns, but sim
back from the tip or crack and flake along the shaft of the ilar durations compared to MUAPs recorded with standard con
needle; however, when disposable electrodes are used, this con centric needle electrodes.30.34.43
cern is eliminated. 53 If a monopolar needle electrode is used The monopoiar needle's impedance was found to be consis
several times (following sterilization), the Teflon may peel off tently lower than that of concentric needle electrodes. 61 At a
the needle's tip and the recording area subsequently increases. It single frequency of 10 cycles/second (Hertz-Hz), the dry
has been demonstrated that progressive Teflon removal from the monopolar needle's impedance was about 1.4 Mil while that of
needle tip to twice the recording surface area of normal results the concentric needle was 4.7 MO. Placing both electrodes in a
in significant MUAP amplitude reduction. I I The amplitude is saline bath for 20 minutes significantly reduced both electrode's
believed to be reduced because the removal of Teflon increases impedances. Although previous studies demonstrated a higher
the metal recording area over which an action potential is dis impedance for monopolar needles than concentric electrodes,6.29
tributed. The MUAP's duration does not change until the ex more recent investigations have not confirmed this finding.
posed length of the needle tip reaches 10 times the original A monopolar needle requires a surface reference and ground
length. At 10 times the exposed needle length, the MUAP area electrode to obtain successful recordings. 32 This may be consid
begins to decline as does the number of turns and phases. ered a minor inconvenience compared to concentric needle elec
The intramuscular sampling area of a monopolar needle is trodes. The reference electrode can be located near the needle's
spherically shaped and hence nondirectional.5 1 The uptake insertion site or over a distant tendinous (electrically silent)
area's radius is approximately 1.5 times that of a standard con region. It is possible for a reference electrode located close to
centric needle electrode (Fig. 3-6A).52 The spherical recording the needle site to record voluntary activity and increase the
area can produce MUAPs with larger amplitudes than those recording's noise level. A too distant reference placement may
recorded with the standard concentric needle electrode, possibly also record more distant coactivated MUAPs or diminish com
because electrical activity from more single muscle fibers is mon mode rejection. It is best to completely relax the limb
A B c o
E-l E-I
~E-! E-2
Figure 3-6. Pictorial depiction of the different needle recording electrodes available and their uptake areas. A, Monopolar needle
electrodes require a separate reference and ground electrode. B,A standard concentric needle electrode is depicted that uses the cannula as a
reference but does need a separate surface ground. C, Single-fiber electrode with E-I as a side port-pickup and the cannula that serves as the ref
erence is shown. Again, a separate ground electrode is required. D, Bipolar concentric needle electrode is described with two recording ports
close to each other. The cannula is the ground while the two central wires are the active and reference electrode. (Modified from Dumitru D,
Walsh NE: Electrophysiologic instrumentation. In Dumitru D (ed): Clinical Neurophysiology. Philadelphia, Hanley & Belfus, 1989, with permission.)
Chapter 3 INSTRUMENTATION - 75
except for the muscle being examined and locate the reference Just as in monopolar recordings, the ground electrode should be
over a nearby bony prominence or tendon. If this fails to reduce placed in a convenient location. The cannula's entire surface is
distant activity, locating the reference or B-2 electrode immedi capable of detecting electrical activity. Whatever portion of the
ately adjacent to the needle insertion site may reduce the muscle cannula is placed into the body has the potential of detecting
activity. The ground electrode is usually placed in a convenient electrical activity. As a result, the cannula's distal portion and
location. It may be of some assistance to use a second subcuta active recording surface may record similar data. The informa
neous monopolar needle instead of a surface disc electrode tion recorded by the cannula, however, is averaged over the
when interference becomes a significant problem. This is be metal surface exposed within the volume conductor that tends
cause the two different electrodes (monopolar and surface disc) to reduce the signal's amplitude compared to that detected at the
are recording slightly different "noise" potentials which are active electrode's surface. In differential amplification, common
being amplified as opposed to rejected. data from both the cannula and active surface lead to common
The monopolar needle may be used occasionally as a cathode mode rejection that tends to reduce the MUAP's amplitude and
to perform near-nerve excitation.s.44.58.60 Caution has been rec background noise compared to monopolar recordings. The end
ommended in stimulating nerves with a needle electrode. 53 The result is a somewhat "quieter" baseline with potentially less
small tip of the needle can concentrate the stimulating current electrical noise and reduced MUAP amplitudes.
over a highly localized region, thereby increasing the current Inserting the cannula deeper into the examined muscle theo
density to a level that may injure nervous tissue. It is suggested retically results in MUAPs slightly larger in amplitude and
that prior to stimulation the Teflon be removed 3-4 mm from longer in duration than those recorded more superficially.6,8 The
the tip to reduce the current density. Stimulating with a deeper the cannula is in the volume conductor, the more metal
monopolar needle is used apparently without detectable neuro lic surface is available for the detected signal to be averaged
trauma by reducing the excitation pulse's duration to 0.05 over.6,38 This is assumed to reduce the signal's amplitude
ms.43.60 It is not necessary to remove the Teflon from a monopo recorded by the cannula and fed into the amplifier, which in turn
lar needle used as a cathode provided the stimulus duration is means there is less in common with the active recording elec
maintained at 0.05 ms or less. trode. 32 As fewer similar signals are subtracted through differen
Commercial needle manufacturers now provide disposable tial amplification, the observed MUAP increases in amplitude.
monopolar needle electrodes at reasonable cost. Disposable This effect does not occur with monopolar needles.
needle electrodes (monopolar and standard concentric) have A study comparing various electrical properties (impedance,
become more popular in light of the prevalence of infectious noise, interference sensitivity, and signal distortion) among five
blood-borne diseases. 33 Although needle quality varies among brands of commercially available concentric needle electrodes
the different companies, those from more reputable firms revealed considerable variability.16 It was concluded that ob
appear to provide stable noise-free recordings comparable to served differences stemmed from diversity in manufacture, ma
those obtained from reusable electrodes. If disposable needle terials, construction, and design. Electrolytic treatment appears
electrodes are used, there is no need to worry about Teflon peel to improve the recording characteristics of all needle brands and
ing with repeated use or infectious disease problems. diminishes the inter-brand electrical variance. The various nee
Standard Concentric Needle Electrode. The standard dles' recording characteristics may affect the MUAP's parame
concentric needle electrode was introduced by Adrian and ters and affect comparison of reference data from one laboratory
Bronk. l This electrode is essentially a hollow stainless steel hy to another. Commercially available disposable concentric
podermic needle (cannula) with a centrally located platinum or needle electrodes adequately compete with nondisposable elec
nichrome-silver wire 0.1 mm in diameter insulated from the trodes with respect to electrical stability and signal fidelity, thus
cannula by a nonconducting epoxy resin. The cannula is bare permitting their use from both a cost-effective and communica
metal with a diameter of 0.3-1.0 mm and a length similar to that ble disease aspect.
of the monopolar needle. 12•41 The tip of the concentric needle Monopolar vs. Standard Concentric Needle Electrodes.
electrode has a beveled cutting edge with a 15-20° angle. 41 The One may anticipate that the ideal needle recording electrode to
150-J..IIll diameter central wire's recording surface is oval-shaped assess MUAPs does not exist. The monopolar and standard con
with an exposed surface of 150 J..IIll by 580 J..IIll (0.08 mm2).12 centric needle electrodes each possess inherent advantages and
The three-dimensional recording region of the concentric disadvantages. To some extent, they both demonstrate variation
needle is a hemisphere with a radius range of 1.0--2.5 mm (Fig. in recording characteristics among different manufacturers. The
3-6B).41 The hemispheric uptake area suggests that the concen directional and depth-dependent properties of the concentric
tric needle has directional recording properties. The cannula's needle should be kept in mind when quantifying MUAP proper
beveled tip acts as a shield preventing the single muscle fibers' ties.6.8 Standard concentric needle recordings may be somewhat
voltages opposite the recording surface from contributing to the more free of electrical interference and background noise than
detected MUAP waveform. This "shield" aspect of the concen monopolar needles, but possess a cutting edge that may damage
tric electrode applies only to the fibers contributing to the tissue. The standard concentric needle does not require an addi
MUAP's negative spike, i.e., within 300 J..IIll of the electrode's tional electrode (reference) that needs to be periodically relo
core. The directional recording characteristics of the standard cated on the patient, but it is more painful than the monopolar
concentric needle electrode are, therefore, quite different from needle. 51 Although the concentric needle may have a slightly
that of the monopolar needle as they relate to those few fibers more uniform recording surface, the sensitive diagnostic para
contributing to the MUAP's negative spike. The recording of meter of MUAP duration appears essentially the same for both
fewer total muscle fibers within the roughly 300-J..IIll hemisphere types of electrodes. 30 In the final analysis, personal preference
uptake area may result in smaller MUAP amplitudes compared and training biases seems to be the dominant factors in deter
to monopolar recordings. mining the type of electrode used in clinical practice. The com
In concentric needle observations. the cannula serves as the petent practitioner, however, should be thoroughly familiar with
reference electrode but a separate ground electrode is required. using both types of electrodes. A sound practice is to develop
76 - PART I FUNDAMENTAL PRINCIPLES
reference data for both types of electrodes in one's practice set electrode should possess an input impedance of 10 MQ or
ting and not mix and match MUAP parameters between labora more,49
tories and needle types. It is the preference of one of the authors Bipolar Concentric Needle Electrode. A bipolar concen·
(DO) to use monopoiar needles when performing routine needle tric needle electrode is similar to a standard concentric needle
electromyographic examinations of multiple muscles, but to use electrode except that a second nichrome-silver wire is located
a concentric electrode when performing quantitative analysis of within the cannula and serves as the electrode's reference (fig.
individual MUAPs from a limited number of muscles. 3-60).6 This reference (E-2) wire is separated from the active
Physical modeling of monopolar and concentric needle elec (E-l) wire and cannula by a nonconducting epoxy resin similar
trodes have verified some but refuted other assumptions made to that of a standard concentric needle. Although the bipolar
in computer models of these two electrodes. 21 - 24 ,35,42 The physi concentric needle is rarely used, some of its properties are worth
cal modeling of the uptake area for these two electrodes verifies discussing. Unlike the standard concentric needle, the bipolar
in that the concentric electrode has essentially a hemispherical concentric needle does not require a separate ground electrode
recording area regarding the fibers comprising the main spike because the cannula serves this function. The active (E-I) and
for the recorded MUAP. Similarly, the monopolar needle reveals reference (E-2) electrodes are located less than a millimeter
a somewhat spherical recording uptake area for the fibers con apart, which enables them to record similar data from a very lo
tributing to the MUAP's negative spike. However, with respect calized or selective region within the volume conductor. As one
to the MUAP's duration, both electrodes' active recording sur would imagine, there is very little electrical noise in these
faces record from a spherical uptake area. The concept of the recordings, Motor unit action potentials observed with a bipolar
cannula shielding the concentric electrode's core from the fibers concentric needle consist of electrical activity from relatively
"behind" it appears not to be true. This is demonstrated by the few fibers and appear very different than those from monopolar
fact that rotating a concentric needle electrode while recording or standard concentric needle recordings. 6,38.46 The duration and
from the same MUAP does not lead to any alteration in the amplitude of a bipolarly recorded potential are markedly re
MUAP's duration. Another interesting aspect of these two elec duced. Additionally, the bipolar concentric electrode is consid
trode types is the fact that most studies have revealed that the erably larger than a monopolar or concentric needle and can be
monopolar needle electrode on average records MUAPs with relatively more painful.
larger peak-to-peak negative spike amplitudes. The physical Snbdermal Electroencephalographic Electrodes. Snb
models show that for a single fiber the same distance from dermal electroencephalographic needles are 10-20 mm long
either needle's active recording surface, the concentric needle and 0.8 mm in diameter and made of stainless steel or plat
records a larger amplitude. However, the rate at which the am inum/iridium primarily used to record evoked potentials. 48
plitude for this single fiber declines with distance is much These electrodes are usually placed just under the scalp and
greater for the concentric electrode. Therefore, large MUAP held in place with tape. The impedance of these needles ranges
amplitudes recorded by monopolar needle electrodes arise be between 3,000 and 10,000 Q but yield evoked potentials that are
cause of the larger recording territory and hence more fibers not significantly different than those obtained by surface elec
within it contributing to the MUAP spike, which more than trodes with impedances less than 5,000 Q.4,21.63 Comparable
makes up for the relatively larger amplitude per fiber recorded evoked potentials can be obtained with needle electrodes of
by the concentric electrode. Finally, actual measurements of higher impedance than surface electrodes because the needle is
MUAPs recorded with concentric needle electrodes in superfi placed within the volume conductor and bypasses the skin. The
cial compared to deeper muscle regions failed to support the signal in effect is detected without difficulty by the needle elec
concept that the more deeply recorded MUAPs should have trodes whereas a surface electrode must have the skin's surface
longer durations and larger amplitudes. 26 The clinical studies barrier considerably reduced to detect the same signal. The in
showed no difference between these two sets of MUAPs with herent impedance of the needle electrodes' metal (stainless steel
respect to duration or amplitude parameters. This is likely a and platinum/iridium) is larger than that of the surface elec
result of modem instruments using averagers capable of opti trodes (gold and silver), and the needle has a considerably
mizing the signal-to-noise ratio sufficiently to detect slight dif smaller surface area than the surface discs. Surface area is a
ferences between the core and cannula signals irrespective of major determining factor when considering impedance and the
tissue depth. smaller the area of exposed recording surface, the larger the im
Single.Fiber Electrode. The single·fiber electrode is basi pedance as it is more difficult for current to flow. These two fac
cally a modified standard concentric needle electrode (Fig. 3 tors, surface area and metal type, most likely account for the
6C),49 The central wire exits approximately 4 mm proximal and different impedances between needle and surface recording
opposite the beveled tip through a side-port in the cannula in electrodes. However, as long as the amplifier's impedance is
stead of extending along the length of the cannula to the beveled substantially larger than that of the needle electrode, an undis
tip.62 While the active recording surface approximates 25 J..llll in torted signal is obtained. The needle electrode does not require
diameter, the cannula's diameter is about 0.5 mm. A separate the skin to be abraded or an elaborate means of securing it to the
ground electrode is required while the cannula serves as the E-2 skull; application is thus relatively easy. The asserted threat of
electrode. The diameter of the E-l recording surface approaches increased infection rates with needle electrodes has not been
that of a single muscle fiber and improves the selectivity of this documented and remains only speculation. 21 It should be real
electrode to record primarily from one muscle fiber. The uptake ized that with a larger number of recording channels-for ex
region of E-l is a hemisphere with a diameter approximating ample in sensory evoked potentials-the use of multiple needle
300 J..llll. 50 The combination of a small active recording surface insertions may become cumbersome. Of note, both electrodes
and an elevated low-frequency filter of 500-1000 Hz enables should be properly sterilized if reused because the surface elec
the single-fiber electrode to record from very small areas. A trode requires skin abrasion exposing it to the patient's serum,
small recording surface gives the single-fiber electrode a large and in this respect is just as contaminated as the needle elec
impedance, which requires that any amplifier connected to this trode piercing the patient's skin. Any device or substance used
Chapter 3 INSTRUMENTATION - 77
AMPLIFIERS
AMPLIFICATION
As previously stated, the magnitude of biologic signals can
range from microvolts to millivolts. Following signal detection
Latency
by the electrodes, the biologic signals must be significantly am Trace Sensitivity Amplitude
plified prior to analysis. One can express amplification in tenns Onset Peak
of gain or sensitivity. Gain may be simply stated as the ratio of
the amplifier's output to its input signal. s3 For example, suppose p.V/div ms p.V
an input signal of 10 JlV emerges from the amplifier's output as A 20 2.8 3.4 78
1 V. The gain in this case is 100,000 (output/input = 1 B 50 2.8 3.4 78
V/O.OOOOI V = 100,000). It is important to note that there are no C 100 2.8 3.4 78
units to the gain value because it is a ratio. Sensitivity, on the
other hand, is the ratio of the input voltage to the size of a CRT figure 3-8. Amplifier sensitivity effect on SNAP wavefonn.
deflection. The CRT's deflection is typically measured in cen Similar to Figure 7 except that the amplifier sensitivity is altered for a
timeters (cm). An amplifier with a sensitivity setting of 10 SNAP. No difference is noted for the various amplifier settings. (From
JlV/cm (10 f.lV/division) means that an input signal of 10 f.lV Dumitru D,Walsh NE: Electrophysiologic instrumentation. In Dumitru
will result in a 1 cm CRT deflection, or each division on the D (ed): Clinical Neurophysiology. Philadelphia, Hanley & Belfus, 1989,
CRT will represent a display magnitude of 10 f.lV (10 f.lV/div). with permission.)
Observing the gain or sensitivity at which a particular re
sponse is elicited is not a trivial matter. In electrodiagnostic med
icine one important parameter is the onset latency of the If we begin at an amplifier sensitivity of 500 f.lV/div, the
compound muscle action potential (CMAP). It is easy to demon CMAP's onset latency is measured at 3.4 ms. Sequentially de
strate the variability of the CMAP onset latency when the same creasing the amplifier's sensitivity results in a progressive in
potential is observed at multiple sensitivity settings (Fig. 3-7).18 crease in the waveform's onset latency to 3.8 ms at 10,000
f.lVIdiv. This example demonstrates the necessity of recording
the amplifier's sensitivity in reporting data from one investiga
tion to another, and also emphasizes the importance of reproduc
ing another laboratory's instrument settings when using their
reference data. Significant shifts in onset or peak latencies are
~ not observed for sensory nerve action potentials, most likely be
2ms cause these waveforms are rather small to begin with and the in
cremental change in sensitivity is comparably smaller than
described above for CMAPs (Fig. 3-8).
INPUT IMPEDANCE
o Amplifiers, in addition to electrodes, also possess an imped
ance. Similar to electrodes, the amplifier's resistance and capaci
tance are considered important parameters, but the inductance is
of negligible magnitude at biologic frequencies of interest. The
electrode and amplifier in combination with the biologic signal
Trace form a relatively simple electronic circuit that obeys Ohm's law:
Sensitivity Latency onset Amplitude
E = I x R. Recall that biologic signals vary over time. Circuits
ms measuring biologic signals approach AC circuits in which the
f.lVldiv mV
A 3.4 term resistance (R) is replaced by impedance (Z) to take into ac
500
B 1,000 3.5
count both factors of resistance and capacitive reactance so that
C 5,000 3.7
Ohm's law becomes E =I x Z. The action potentials in the body
23 serve as the battery or voltage source (EtotaJ ), while the imped
D 10,000 3.8 23 ance for the recording electrode (z"lec) and amplifier (Zamp) can
be simplified for discussion purposes as two separate compo
Figure 3-7. Amplifier sensitivity effect on CHAP onset la nents in series (Fig. 3-9). In this simple series circuit, the current
tency. Decreasing the amplifier's sensitivity (A-D) demonstrates a from the biologic source is the same across both z,,'ec and Zamp;
prolongation in the CMAP's onset latency (table). (Modified from however, there is a different voltage drop across each of them
Dumitru D,Walsh NE: Electrophysiologic instrumentation. In Dumitru summating to the signal generated in the body, i.e., Etolal .53 As
D (ed): Clinical Neurophysiology. Philadelphia, Hanley & Belfus, 1989, stated in the introduction, the total voltage drop in the whole cir
with permission.) cuit is divided among the individual voltage drops across each of
78 - PART I FUNDAMENTAL PRINCIPLES
100 mY 20 Mn 10 Mn 33.3 mY
100 mY 10 Mn 10 Mn 50.0 mY
100 mY 5Mn 10Mn 66.7 mY
100 mY IMn 10Mn 99.9 mY
=
Using the voltage divider equation (E.",p E.- Xz..,.;Z.lec + z..,p) one can see
that most of the biologic signal will be detected by the amplifier when the im
pedance of the electrode is Significantly less than that of the amplifier.
A B
"v
20 Y
200.000p.V
eM RR = 10,000
I
Figure 3-10. The results ofdifferentlaJ amplification are depicted.A,A signal is connected to both amplifiers in a common mode (same
signal to each amplifier) manner. The gain is one. B. In the difference mode montage the gain in 10,000.The common mode rejection ration
(CMRR) is 10,000 to I. (From Dumitru D.Walsh NE: Electrophysiologic instrumentation. In Dumitru D (ed): Clinical Neurophysiology. Philadelphia.
Hanley & Belfus, 1989, with permission.)
mismatch that results in slightly different signals being pre HIGH- AND LOW-FREQUENCY FILTERS
sented to the amplifier. These unwanted differences are magni
fied and not canceled. If one wishes to eliminate our BIOLOGIC SIGNALS
environmentally prevalent 60-Hz interference presenting to both
electrodes, the more alike the electrodes are, the greater the Biologic signals observed in electrodiagnostic medicine can
chance of more perfectly subtracting 60 Hz as a common mode be thought of as the sum of time varying sinusoidal waveforms
signal. Two electrodes constructed of different materials may with different frequencies whereby their individual phases and
amplify undesired environmental noise because of an imped amplitudes summate or cancel to reproduce the original wave
ance mismatch. form.47 An analysis of these potentials can be considered if one
The effectiveness of an instrument's differential amplifica conceptualizes them to consist of an infinite series of sine waves
tion can be quantified by its common-mode rejection ratio with different amplitudes and frequencies. This complex mathe
(CMRR). The CMRR is the summated output of the amplifiers matical process of harmonic or frequency spectrum analysis
when a signal is amplified differentially compared to when the can be simplified for discussion purposes. 47 Let us consider a
same signal is presented in common mode. For example. if a 20 series of five sine waves with particular frequencies, arbitrary
J.lV signal is presented to both the E-l and E-2 ports (common amplitUdes scaled relative to each other, and all in phase with
mode) of an amplifier with respective amplifications of 10,000 respect to each other (Fig. 3-11A). The individual waveforms in
and 9,999. the amplified summated output signal is 20 IlV (Fig. our example have specific frequency characteristics. We define
3-10). In this instance the common mode gain is 1 (20 11V120 a frequency as the number of times the same event or cycle
J.lV = 1). Let us now apply this same 20 J.lV potential differen occurs in one second, i.e., cycles/second. As noted above, one
tially, i.e., 20llV is fed into the noninverting amplifier port and cycle per second is called a hertz and abbreviated Hz.15 In elec
o J.IV is presented to the inverting amplifier port. The same am trophysiology, events take place over relatively short time spans
plifiers now yield a summated potential with a magnitude of and can have frequencies of thousands (kilo or simply Uk") of
200,000 J.lV resulting in a differential to common mode gain times per second (kilohertz or kHz). Summating all of the
ratio of 10,000 (200,000 IlV/20 IlV = 10,000). This ratio is the given waveforms in our example on a point-for-point basis re
CMRR, or in this instance 10,000 to 1. Another way of thinking sults in a net waveform approximating a square wave. It is im
about the CMRR is that any difference detected between elec portant to appreciate how choosing the appropriate number of
trodes is amplified 10,000 times more than when the same sine waves with individual frequencies generates a summated
signal is detected at both electrodes. The majority of commer waveform whose appearance is distinctly different than each
cially available instruments have CMRRs of 10,000: I or subcomponent waveform (Fig. 3-IIA).
greater. It is common to express the CMRR as a decibel (dB) From the above discussion it can be seen that our square wave
power function, where a dB 20 log CMRR. In the above ex actually consists of a series of subcomponent waveforms of both
ample, 20 log 10,000 = 80 dB (20l0g10,000 = 20l0g104 = relatively high and low frequencies. Adding more appropriate
4(20)log1O =80 db). subcomponent higher frequency waveforms results in a final
80 - PART I FUNDAMENTAL PRINCIPLES
followed by the capacitor, we can measure the voltage drop of the capacitor and resistor, we can allow most of the low fre
across the capacitor by connecting an amplifier across the two quencies to drop across the capacitor by increasing its imped
terminals of the capacitor. The voltages contained within the ance greater than that of the resistor described above so that the
mixed-frequency signal representing the waveform must be di only signals measured by the amplifier are low frequencies. In
vided between two voltage drops: one across the resistor and the this way, the low frequencies can be amplified and detected by
other across the capacitor. Remember that a voltage divider is the instrument. In short, the high frequencies were not allowed
formed by these two "in series" electronic components. The to pass onto the amplifier, but the low frequencies dropped their
higher frequencies in the signal are not impeded by the capaci voltage across the capacitor thereby being amplified and subse
tor because the equation Zc = 1/(21tfC) tells us that as Hf' in quently observed, i.e., a low-pass filter. The amplifier measures
creases, the capacitor's impedance diminishes. Therefore, the voltage across the capacitor. If all of the voltage dropped across
capacitor does not impede the higher frequencies contained in the capacitor, then it is high on one side of the capacitor and es
the waveform and there is no voltage drop across the capacitor sentially zero on the other side. The amplifier subtracts the zero
for the amplifier to measure. All of the voltage for the high fre voltage from the high voltage for the passing low frequencies
quencies drops across the resistor and never gets to the ampli and the voltage amplified is effectively the same as that in the
fier. Another way of thinking of this concept is to realize that body.
the capacitor offers minimal resistance to current flow for the If the order of the resistor and capacitor is reversed, the am
high-frequency signal. Since the total voltage is divided be plifier records any voltage drop occurring across the resistor
tween the resistor and capacitor, a minimal resistance to the ca (Fig. 3-13B ). The voltage divider equation must be rewritten to
pacitor means that most, if not all, of the voltage drop in the reflect our measuring amplifier now placed across the:
circuit must occur across the resistor. The amplifier, however, is
not placed across the resistor and therefore this voltage drop is E _ &olal xZR
amp- ZR+ZC
not detected resulting in a "filtering" of these signals, preclud
ing them from being observed on the CRT. This can be ex For a mixed signal, the subcomponent high frequencies will
pressed mathematically by using the voltage divider equation pass unimpeded across the capacitor (impedance drops to zero
discussed previously where the waveform's voltage detected at by 1/(27tfC) to drop their voltages across the resistor to be mea
the amplifier (Eamp) is expressed in terms of the waveform's sured by the amplifier. This is because Eamp =EwtaJ as '4I(ZR +
voltage content for a particular frequency <EtotaJ and the imped =
0) 1. The waveform's subcomponent low frequencies all drop
ances of the resistor (ZR) and capacitor (Zc): across the capacitor, but since the amplifier is not connected
across it, we are not able to detect this voltage drop. For the low
E _ &otaIXZc frequencies, the impedance of the capacitor (Zc) is significantly
amp- ZR+Zc
greater than ZR causing Eamp to approach 0, because Erotal x ZR
For a high frequency, the capacitor's impedance approaches divided by the large quantity Zc equates to a very small number.
zero (plug zero into the above equation in place of Zc in the nu The end result is a high-pass or low-frequency filter.
merator and denominator) and the voltage observed by the am A completely different approach regarding the filtering of bi
plifier also approaches zero, thereby eliminating the high ologic signals is the application of digital filtering, which is in
frequencies, i.e., Eamp =0 or close to it. creasingly used in modern apparatuses. Digital filtering can be
Low frequencies may be allowed to pass onto the amplifier if done in both the time and frequency domain. A simple example
the resistor's impedance is substantially lower than that of the is to calculate the average values of the previous and next signal
capacitor. In this case, the voltage for the low frequencies in the value resulting in a smoothing of the signal. The digital repre
mixed signal pass onto the amplifier without change because sentation of the signal can be transformed to the frequency
the above equation reduces to Eamp =Biotal when Zc» ZR be domain enabling the selective removal of chosen frequencies.
= =
cause Zc/(ZR + Ze) ZclZc 1. The high frequencies experi After this, the signal is shown again as a function of time.
ence a voltage drop across the resistor, but since the amplifier is Digital filtering results in complete and sharp removal of the
not connected across the resistor, they are not observed. The low chosen frequency bands, in contrast with the hardware filtering
frequencies, however, could pass across the resistor but not the just described. Analog filters are subject to drift and variations
capacitor, because the equation 1/(21tfc) states that for low fre in frequency response due to temperature changes. Digital fil
quencies an impedance is present. Depending on the characteristics ters are very stable and do not change with time.
A B
Zc
To To
CRT CRT
Figure 3-13. Two resistor/capacitor (RC) circuits are depicted representing analog filters.A,A high-frequency (low-pass) filter is
formed and the high frequencies drop across the resistor while the low frequencies drop across the capacitor to pass onto the amplifier. S,The
low frequencies drop across the capacitor (low-frequency filter) while the high frequencies drop across the resistor to be passed onto the ampli
fier (high-pass filter).
82 - PART I FUNDAMENTAL PRINCIPLES
\
sponse seems smaller and appears to be developing a third or
negative phase. Quantitatively, the amplitude has decreased
16.9% while the peak latency has shortened 6.0%, but the onset
latency has not changed. A 28.5% reduction in negative spike
duration has also occurred. An additional 3-fold increase in the
low-frequency filter (300 Hz) produces a 53.8% reduction in
amplitude and a 9.0% shortening of the peak latency compared
to a waveform recorded with a lO Hz low-frequency filter. The
onset latency remains unchanged, but the negative spike dura
o 00
tion has decreased 42.8% from the first response. Note that the
Frequency
morphology of the potential is now clearly triphasic: negative
Figure 3-14. Frequency bandwidth. Simple diagram representing positive-negative.
a bandwidth "viewed" by the instrument once the filters have re We may return to the concept of segmental subcomponent
stricted the frequencies passing onto the amplifier. (From Dumitru D. frequencies to explain why the above SNAP underwent the ob
Walsh NE: Practical instrumentation and common sources of error. served changes when elevating the low-frequency filter. The
Am J Phys Med Rehabil 1988;67:55-65. with permission.) waveform'S initial departure from the baseline occurs over a rel
atively short time period. This portion of the waveform has min
imal amplitude contribution from the low frequencies contained
Most commercially available instruments consist of variable in the potential, i.e., the higher frequencies predominantly influ
low- and high-frequency filter systems that can be adjusted by ence this aspect of the waveform. Because elevating the low
the clinician to optimize the frequency content of the signal frequency filter does not affect high frequencies, it should now
under investigation and limit undesired noise. This low- and be clear why the onset latency (high frequency) of the potential
high-frequency filter combination constitutes a "window" to ob did not change. In short, the waveform's onset goes from a flat
serve a relatively limited frequency domain referred to as a baseline to an abrupt negative deflection over a relatively short
bandwidth (Fig. 3-14). The frequencies above and below the
bandwidth's limitations are severely attenuated by the low- and
high-frequency filters, respectively. It is important to note at this
point that low and high are relative terms that depend on the J20p.V
content of the waveform under investigation. Because filters can 2ms
potentially eliminate important waveform subcomponent fre ~
quencies if set improperly, the waveform's morphology can be
significantly altered. The clinician, therefore, must be thor
oughly familiar with the effects high- and low-frequency filters
have on normally recorded signals.
J1-
by high frequencies. Since we elevated the low-frequency filter,
there was no effect on the high frequencies with the potential's Sms
onset remaining unchanged. This exemplifies why the low-fre
~
quency filter is also called a high-pass filter.
Although the negative peak's inflection point has a short time
span (high frequency), that portion of the waveform preceding
and following the peak covers more time and is influenced by
~
the summated magnitudes of the relatively lower frequencies
(Fig. 3-11). We might anticipate that elevating the low-fre
quency filter would prohibit the frequencies that require more
time to be resolved from contributing to the waveform. In one
sense, the low frequencies are being sequentially extracted, re Low Latency
sulting in a waveform with a progressively greater amount of Trace frequency Amplitude
high frequencies. Preventing electrical signals from contribut filter Onset Peak
ing to the potential's total signal content would be expected to Hz ms mV
result in a smaller potential, i.e., removing frequencies from the
waveform means there is less contained in the observed signal. A 1 3.5 6.7 21
In other words, removing signals from the waveform would be B 10 3.5 6.3 21
expected to reduce and not increase its magnitude. Additionally, C 100 3.5 5.0 11
that portion of the waveform from which the low-frequency sig
nals were removed could also be expected to occur sooner in Figure 3-16. Low-frequency filter elevation effect on a
time, because the remaining higher frequencies now have a CHAP. Elevating the low-frequency filter on a CMAP has very clear
greater influence thus biasing the potential to a higher-fre effects similar to those observed for the SNAP. (From Dumitru D,
quency content than previously. Higher frequencies occur more Walsh NE: Practical instrumentation and common sources of error.
rapidly per unit of time than lower frequencies, thereby biasing Am J Phys Med Rehabil 1988;67:55-65, with permission.)
the portion of the waveform with less low frequencies to occur
sooner in time. These two observations are reflected in a SNAP
with less amplitude and a shorter peak latency. Additionally, re onset latency. The slow return of the potential (low frequen
moval of low-frequency signals also results in a negative spike cies) is also truncated, thereby reducing the observed poten
that requires less time to develop. Aside from the onset latency tial's total duration (Figs. 3-15 and 3-16).
(high frequencies), the entire waveform shifts left on the CRT,
i.e., it occurs sooner (Fig. 3-15). HIGH-FREQUENCY (LOW-PASS) FILTER
The observation of a third phase being produced with eleva
tion of the low-frequency filter also can be explained by con As previously stated, biologic waveforms have both low
sidering the concept of subcomponent frequencies. Increasing and high-frequency subcomponents. The high frequencies of
the low-frequency filter essentially removes the low frequen most waveforms are contained in the portions of the potential
cies contributing to the waveform. The waveform, therefore, that change rapidly, e.g., rise time and inflection points. 20 As it
now consists preferentially of higher frequencies. The remain is reasonably easy to change an instrument's filter settings, the
ing higher frequencies are no longer influenced by the lower clinician should be aware of how a high-frequency filter that is
ones and can be observed. Higher frequencies cycle or recur set too low can distort a waveform. The most practical way to
repeatedly more often over the same time period compared to demonstrate these waveform changes is to evoke an an
the low frequencies and therefore have more phases. By re tidromic SNAP or CMAP and sequentially lower the high-fre
moving the low frequencies from a waveform, one would an quency filter in the following steps: 10,000, 2,000, 1,000, and
ticipate that the remaining potential would display more 500 Hz. 18,45 The low-frequency filter remains at 10Hz through
phases. Another way of thinking about this process is that sig out the entire example. Similar waveform parameters to those
nals resembling the DC component (relatively low frequency) previously discussed will be investigated: onset latency, peak
of the potential are extracted, leaving the signals that more latency, negative spike duration, and amplitude (Figs. 3-17 and
closely resemble AC (relatively high frequency). In reality we 3-18).
are speaking about voltages versus current, as this is what the Lowering the high-frequency filter incrementally progres
instrument actually measures. An alternating voltage tends to sively removes the waveform's higher frequencies, leaving a
have the same amount of magnitude above and below the potential with a relatively lower frequency content below the
baseline. A waveform that consists primarily of higher fre upper cut-off limit. One could anticipate that lower frequencies
quencies or alternating voltages begins to resemble a sinu occur over a relatively longer period of time compared to
soidal curve. This is exemplified by elevating the low-frequency higher ones. The portions of the waveform that remain for ob
filter while recording a CMAP (Fig. 3-16A-C). Note how the servation may very well occur comparatively later in time.
CMAP begins to resemble an alternating sinusoidal curve as These predicted findings are indeed found clinically (Fig. 3
more and more low frequencies are prohibited from contribut 17).18 A 20-fold decrease in the high-frequency filter from
ing to the potential. The end result of this process is an addi 10,000 Hz to 500 Hz results in an II % delay in the onset la
tional phase. Increasing the low-frequency filter above the tency and a 27% prolongation in the peak latency. The ampli
frequencies contained in a waveform decreases amplitude, tude decreased about 16% while the negative spike duration
shortens peak latency (pbase lead), decreases negative spike increased 30%. Similar changes are demonstrated for a CMAP
duration, increases phases, but does not significantly affect with the exception that the amplitude changes little, if at ail, as
84 - PART I FUNDAMENTAL PRINCIPLES
~
J10mV used. A notch filter is a filter with the selective ability to
5ms remove only designated frequencies from the waveform. The
~
50/60-Hz signal originating from some power source contami
nates the potentials under investigation. It is also possible in
some instruments to impose a notch filter during the sensory
and motor conduction portion of the examination, although
little signal distortion usually occurs to either SNAPs or
CMAPs during the nerve conduction examination from notch
filter application. Similarly, little signal distortion occurs to
High Latency fibrillation potentials or MUAPs following implementation of
Trace frequency Amplitude a 60 Hz notch filter. However, it is possible to distort the posi
filter Onset Peak tive sharp wave somewhat during the needle electromyo
graphic examination if a 60-Hz notch filter is used (Fig. 3-19).
Hz ms mV The frequency content of this signal certainly contains fre
A 10,000 3.3 6.9 21 quencies in the 50-60 Hz range with a distinct "notch" noted
B 2,000 3.5 7.1 21 in the terminal negative phase of the positive sharp wave. As
C 1,000 3.8 7.3 21 long as the practitioner is aware of potential signal distortion
D 500 4.2 7.5 21 that can occur with notch filters, they can be used rather effec
tively. Not uncommonly, immediately following insertion of
figure 3-'8. High-frequency filter effect on a CHAP. Minor the needle electromyographic electrode into muscle tissue, a
changes in the CMAP are described as the high-frequency filter is low considerable 6O-Hz signal may be observed which responds to
ered, suggesting that this waveform contains a substantial amount of the notch filter. However, after a few minutes the interference
frequencies below 500 Hz. (From Dumitru D,Walsh NE: Practical in may subside, most likely a result of a reduction in needle im
strumentation and common sources of error. Am J Phys Med Rehabil pedance following an interaction with body fluids. Therefore,
1988;67:55-65, with permission.) from time to time during the needle examination it may be
Chapter 3 INSTRUMENTATION - 85
A
SOUND
After the biologic signal has been amplified, but before it is
digitally processed, the energy from the signal is converted into
~50I.IV sound through a loudspeaker. The sound of MUAPs is particu
larly important to both potential recognition and criteria for
10ms analysis. Normal and pathologic muscle potentials investigated
with needle electrodes produce very characteristic sounds that
help identify them. Biologic signals, therefore, are analyzed
from both a visual and acoustic standpoint. The proximity of a
potential also can be qualitatively judged by its sound proper
ties. High-pitched sharp sounds signify that the needle electrode
B is very near the site of action potential generation. Low-pitched
rumblings suggest that one is relatively far from the site of elec
trical activity. A clinician's training is not completed until one
J50I.IV
can identify normal and abnormal potentials by both sight and
5ms sound.
handles this is usually not transparent to the user. It is the re CMAPs. For example, a sensitivity of 1,000 /lV/diY results in
sponsibility of the clinician to understand and use the correct the amplitude marker progressing vertically in 9.7 /lV incre
preset conditions of the apparatus. ments (1,000 IlV/div x 10 div/screen xl screen/l024 points =
Unfortunately, the majority of instruments available can pro 9.7/lV/div). Similarly, a sensitivity of 10,000 /lV/div causes the
vide approximately 600-1024 discrete vertical resolution or amplitude scale to change in 97 /lV steps. As noted above, using
amplitude points representing either millivolts or microvolts too low sensitivity (waveform occupying a small portion of. the
with respect to the screens resolution. 13 In this case, the screen screen) does not permit one to assign enough points of resolu
resolution is obviously considerably lower than that of the AID tion to differentiate relatively small changes in the waveform
converter. This limitation in screen resolution is often made (Fig. 3-20).
worse by the habit of many manufacturers to display the signals
in windows covering only part of the screen. The clinician has HORIZONTAL RESOLUTION
the responsibility of manipulating the instrument's gain or sen
sitivity so that the complete waveform occupies approximately Two relatively simple requirements must be fulfilled for ade
one-half the CRT's vertical height. If the amplifier's sensitivity quate horizontal waveform analysis: (1) total screen analysis
is adjusted so that the waveform completely fills the CRT, any time must be sufficient to encompass the entire potential under
variation in the signal or baseline may overwhelm the number investigation; and (2) screen resolution (dwell time or the in
of vertical resolution points. This can cause the waveform to verse of the sampling frequency) must be sufficient to resolve
extend beyond the upper and lower extremes of the CRT, result the signal's most rapid changes. The horizontal portion of the
ing in a loss of potentially valuable information (Fig. 3-20). A CRT screen is a time scale usually measured in milliseconds
waveform that occupies significantly less than one-half the CRT and divided into 10 equal divisions. The number of resolution
screen can have significant portions of its signal distributed be points across the total screen is fixed by the manufacturer and
tween resolution points and again be lost to measurement. typically contains 512 or 1024 data points to resolve the wave
Fortunately, because the AID converter's resolution far exceeds form. The clinician has the option of designating the amount of
that of the screen, it is possible for instruments manufactured time allotted for analysis over the screen's width, i.e., the time
presently to sample the waveform at a high resolution and dis chosen by the instrument's operator determines oyer how much
play the waveform at many different sensitivities without com time the limited number of data resolution points are distrib
promising the waveform's morphology significantly until the uted. Assigning relatively large time intervals to the whole
extremes of the AID converter's resolution is reached. screen results in less resolution to accurately define minor
The above concepts can be clarified if one considers an in waveform changes. The resolving power of the instrument is re
strument to contain 1024 points of vertical resolution for a duced because each individual point on the screen is expected to
screen with 10 vertical divisions. If the sensitivity is initially set cover more time. However, decreasing the total screen time
at 10 /lV/diy, as used in sensory nerve conduction studies, the allows each point to be responsible for smaller portions of the
instrument's amplitude markers can move in 0.097 /lV incre waveform, thereby increasing the likelihood of detecting minor
ments. This incremental amplitude designation can be calcu signal variations. This can be understood by providing a few
lated as follows: 10 /lV/div x 10 div/screen x 1 screen/1024 simple examples.
points = 0.097 /lV/point. If the sensitivity is changed to 1 Let us assume that there are 1000 points of resolution across
/lV/div, the amplitude marker now travels vertically in 0.009/lV the screen. If we adjust the instrument so that an entire screen is
jumps (l/lV/div x 10 div/screen xl screenl1024 points = 0.009 assigned 1,000 ms (1 second), our sweep speed is 100 ms/div
/lV/pt). An amplifier with less sensitivity is used for evaluating (1,000 ms/10 divisions = 100 ms/div). The instrument's resolu
tion for the present set of parameters can be calculated by con
sidering the number of points and time across the entire CRT
B c
..
screen. The CRT screen's resolution is 1,000 points of resolu
tion per 1,000 ms or 1 pointll ms (1,000 points/1 ,000 ms = 1
. ,., j
pointll ms). Recall that the dwell time is the time that passes
before the computer analyzes the next point and in this case is 1
ms per 1 point (1 ms/1 point). The sampling rate or sampling
r\ /
f I
E F frequency has already been stated at 1,000 points/l sec (i.e.,
1,000 Hz), and is the reciprocal of the dwell time or number of
\
~-.!
I
i \
\!
\ .. j
points sampled each second. The sampling frequency is typi
cally expressed in hertz (cycles/second) and for our example it
becomes: 1,000 points/1 ,000 ms = 1,000 points/l sec = 1,000
Figure 3-20. The effect of analog-to-digital conversion on Hz. If for the same 1,000 CRT screen points we can now assign
signal of different amplitude. Sine waves of three amplitudes (A. B, a total of 100 ms across the screen, a new dwell time of 0.1
C) are digitized using vertical intervals of equal size. At each step, the ms/point is created (100 ms/1,000 points =0.1 ms/point). The
amplitude, marked by a dot, is measured.These measures are shown at new sampling frequency is 10,000 Hz (l pointlO.l ms x 1,000
the bottom (0, E. F) where the dots are connected by straight dashed ms/1 sec = 10,000 points/1 sec = 10,000 Hz). It can be seen
lines.The' signal in trace "A" exceeds the vertical range of the digitizer from the above example that for the same number of points
and is distorted in the digital representation in trace "0". The signal in across the screen, the resolution is increased by assigning less
trace "8" fills about one-half of the digitizer range and is fairly well re time to the same number of points. The resolution increased 10
solved in trace "E". The signal in trace "C" fills only a small portion of fold for one-tenth as much time, i.e., from 1 ms/l point (1,000
the total vertical range and is poorly resolved in trace "F". (Modified Hz) to 0.1 msll point (10,000 Hz). In other words, for a CRT
from Spehlmann R: Evoked Potential Primer. Stoneham, MA, screen of 100 ms there are 10 resolution points every 1 ms in
Butterworth-Heinemann, 1985.) stead of 1 resolution point every 1 ms as there are for a total
Chapter 3 INSTRUMENTATION - 87
A B c
has an upper limit subcomponent frequency of 5,000 Hz (1 rise
=
time/O.2 ms X 1,000 msll sec 5,000 rise timesll sec 5,000 =
•
Hz). The minimum sampling frequency (Nyqvist frequency) is
twice the highest subcomponent frequency, yielding 10,000 Hz
.....J (2 x 5,000 Hz = 10,000 Hz). To ensure an accurate reproduction
o 2. 4 6 a 10 0 2 . . G 8 10 o 2 8 6 e 10 '''' of the signal, a sampling frequency of 3 times the Nyqvist fre
(ms) (ma) (rna)
quency (30,000 Hz, or 6 times the rise time frequency) may be
D E F used. A sampling frequency of 30,000 Hz means that the wave
/. i\ ,1\" form is sampled once every 0.033 ms (30,000 Hz = 30,000
\ f\ !\ pointsll,OOO ms = 1 point/0.033 ms). If the screen contains
\j V V\ 1,000 resolution points, our sweep speed (number of ms/divi
sion) should be set at 3.3 ms/div (0.033 ms/] point x 1,000
FIgure 3-21. The relationship between sampling rate and points/l screen x 1 screenllO divisions = 3.3 msldiv) to provide
signal frequency. Effects of different signal frequencies at the same a sampling frequency of 30,000 Hz. An instrument with 1,000
sampling rate. Sine waves at three different frequencies (traces A. S, C) points of resolution across the screen and a sweep speed of 3.3
are sampled at the same rate. At each sampling interval. their ampli ms/div should adequately resolve the given rise time of a single
tude is marked by a dot. These dots, connected by straight dashed lines muscle fiber potential without difficulty. If our instrument had
are shown as a digital display at the bottom (traces O. E, F). The sine 500 points of resolution for the same waveform, we would need
wave in trace "An is sampled about 14 times per cycle and well de a sweep speed of 1.65 ms/div (0.033 ms/point x 500 points/I
picted in the digital representation in trace "0".The sine wave in trace screen x 1 screenllO div = 1.65 msldiv). This finding simply im
"S". being sampled at a rate only 6 time higher than its own frequency. plies that an instrument with half as many screen resolution
is depicted with less but still fair detail after digitization as shown in points requires a sweep speed twice as fast as a comparable in
trace "E".ln contrast, the sine wave in trace "C", being slightly above strument with twice as many resolution points for the same op
the critical value of one-half the sampling rate is not resolved ade timal signal reproduction. In short, increasing the sweep speed
quately in the digital representation in trace "F" showing fewer peaks decreases the total time assigned to the screen, thereby allowing
than the analog waveform and is an example of aliasing. (Modified from the same number of resolution points to be applied over a
Spehlmann R: Evoked Potential Primer. Stoneham, MA. Butterworth shorter interval. For example, changing the sweep speed from 5
Heinemann, 1985.) msldiv to 1 msldiv is what is meant by "increasing" the sweep
speed. Screen resolution and waveform subcomponent fre
quency resolution are interrelated (Table 3-3). This process re
CRT screen time of 1,000 ms. The more points per millisecond, sults in assigning more resolution points to better define rapidly
the greater the resolution of the screen, which in tum allows the changing portions of the waveform. Incidentally, a high-fre
instrument to better define portions of the waveform occurring quency filter setting of at least 10,000 (2 x 5,OOO-rise time)
very rapidly (high-frequency subcomponents). If the high fre should be provided to avoid waveform distortions from too low
quencies are adequately resolved, there is no difficulty in accu a high-frequency filter.
rately defining the low frequencies as there are more than
enough points of resolution for the slowly changing aspects of LATENCY MEASUREMENT
the waveform.
Recall that a biologic waveform may be considered to consist Another important issue to consider with respect to horizontal
of a series of low- and high-frequency subcomponent sine screen resolution is the accurate measurement of waveform la
waves. To display a sine wave digitally, a minimum of two reso tency parameters. It can be helpful to know the time of occur
lution points are required per cycle. As a result, the instrument's rence for particular portions of a waveform, e.g., onset or peak
sampling frequency must be at least twice the highest subcom latency. Should a clinically relevant aspect of a potential that re
ponent frequency of that sine wave to minimally resolve the quires measurement lie between two horizontal resolution points,
signal. This critical sampling frequency is known as the Nyqvist one must take the next available higher or lower screen point The
frequency.48 The Nyqvist sampling frequency only provides the sweep speed also affects the accuracy of time measurements. For
minimum resolution frequency and does not guarantee that the
waveform will be sufficiently reproduced without distortion. It Horizontal Screen Resolution
Table 3·3.
is a good practice to ensure that the instrument's sampling fre
quency is several multiples of the Nyqvist frequency. If the sam Required
pling frequency of the instrument is insufficient to resolve the Rise Waveform High Sampling Sweep
signal's subcomponent frequencies, the recorded waveform will Time Frequency Frequency Resolution Frequency Speed
be distorted (Fig. 3-21). This distortion has the effect of not (ms) (Hz) (Hz) Points (Hz) (ms/div)
recording all of the signal with a potential for missing various 0.2 5,000 10,000 1000 20,000 S.O
components. A reduction in the waveform's components, partic 10,000 500 20,000 2.5
0.2 5,000
ularly if entire phases are eliminated, has a tendency to make
the waveform appear as if it contains lower frequencies than it 0.2 5,000 10,000 250 20,000 1.25
really does. The effect of reducing a waveform frequency con 0.5 2,000 4,000 1000 12,000 8.3
tent through inappropriately low sampling frequencies is called 0.5 2,000 4,000 500 12,000 4.2
aliasing. A few simple examples may help explain this impor
The high-frequency filter (HF) is 50% greater than the high·frequency content
tant concept. of the waveform under discussion to prevent any filter distortion. A screen
Let us begin with a single muscle fiber potential with a rise width of 10 divisions is assumed for these examples. The rise time estimates
time (high-frequency SUbcomponent) of 0.2 ms. The rise time the highest frequency portion of the waveform.
88 - PART I FUNDAMENTAL PRINCIPLES
~50 #LV
ANALOG DIGITAL
STIMULUS.
-A,/D
,! ' . : '
•
•
; .!•! , RESPONSE 1
CONVERSION
..
BINS
- ; ! . !
RESPONSE 2
EPOCH
o 100
, 200msec
D/A
CONVERSION
- ••
Rl
Figure 3-23. Analog-to-digital conversion.Two rather "noisy" analog signals are digitized through AID conversion.The two digital responses
+ ~...+ Rn
n
are then summated. Random signals phase cancel while similar signals summate.The summated response is then divided by 2 and the process is re
peated. For however many averages are performed, the composite signal is divided by the total number of waveforms so that each waveform has
equal weight in the final averaged waveform.The final digital waveform is then converted back into an analog signal.This sequence of events depicts
the manner in which potentials are averaged to improve the signal-to-noise ratio. (Modified from Spehlmann R: Evoked Potential Primer. Stoneham,
MA, Butterworth-Heinemann, 1985.)
or negative. An example is the measurement of medium- and let us assume a single stimulus is delivered to a nerve and the
long-latency reflexes. In this case it is necessary to rectify the ensuing signal has an amplitude of2 tJ.V, while the noise ampli
signal before averaging, i.e., to make all voltage differences be tude is 4 tJ.V. The SIN ratio is equal to 112 (SIN = {2 tJ.V x
tween the two recording electrodes of the same sign (either (..Jl)}/4 tJ.V = 112), which means that the surrounding noise is
positive or negative). In this way a modulation of the EMG twice as big as the signal and will obviously obscure the signal
output can be measured by adding up all stimulus-related am from optimal analysis. If we now perform 4 averages, the SIN
plitude changes in the surface EMG. ratio improves to 1 (SIN = {2 tJ.V x (..J4)}/4 tJ.V = I), implying
that the comparative, one trace versus 4, SIN has been en
Signal-to-Nolse (SIN) Ratio hanced by a factor of 2, i.e., the second SIN of 1 is twice that of
The purpose of averaging is to improve the signal's ampli the previous SIN of 1/2. A SIN of 1 suggests that 4 averages
tude compared to that of the surrounding noise's amplitude, have resulted in a signal that is the same size as the noise.
i.e., the signal-to-noise (SIN) ratio. Once the SIN ratio has Continued averaging to 64 trials improves the SIN by a factor
been optimized, averaging no longer provides additional infor of 8, and the signal is now 4 times that of the noise. The
mation. Unfortunately, there are a number of regularly occur number of averages required to best define a response has a
ring biologic and environmental signals (EEG, ECG, 60-Hz somewhat arbitrary end-point. If the investigator suspects that
line interference, and others) that can obscure the desired averaging is required, the number of averages should be set rel
signal even though they are not time-locked. A portion of the atively high, but stopped when the signal no longer appreciably
60-Hz interference from artificial current/voltage generators changes with additional averages and the baseline noise level
may be reduced if a stimulus rate not evenly divisible into 60 has stabilized. A good practice is to repeat a similar set of aver
is used (e.g., 2.8 Hz). Obviously, it is impossible to eliminate ages to confirm the waveform's reproducibility. In order to
all extraneous signals from contaminating the desired wave judge the relative amplitude of remaining noise in relation to
form, but averaging and appropriate stimulation rates can help the response after averaging it is very useful to have a prestim
considerably. ulus interval. This enables the clinician to estimate the amount
It is known that there is a nonlinear relationship between the of baseline noise and can be helpful in determining if a real
number of responses averaged and the SIN ratio.48 From a prac time-locked response is present in the signaL It is possible that
tical standpoint, averaging enhances the SIN ratio by a factor many thousands of averages are required to define a potential,
that is the square root of the number of averages performed rendering its recording impractical, particularly if a poor
(SIN oc ..J#averages). This statement can be expressed mathe methodology for recording is used. The clinician must ensure
matically by setting the SIN ratio equal to the signal's ampli impeccable recording technique with respect to reducing skin
tude (S) times the square root of the number of averages (vn), impedance, securing properly functioning electrodes with suf
which is then divided by the random noise's amplitude (A): ficient electrolyte cream to the patient, and providing an ade
SIN = (S x (..In)) -;. A. To illustrate the number of averages re quate stimulus to evoke the desired response. Averaging cannot
quired to make an appreciable difference in the detected waveform, replace good technique.
90 - PART I FUNDAMENTAL PRINCIPLES
CATHODE RAY TUBE (CRT) DISPLAYS then became possible for the instrument to repetitively generate
the stored signal without having to continuously shock the pa
CATHODE RAYTUBE tient. The commercially available instruments presently raster
or continuously regenerate the response multiple times per
A cathode ray tube is an electronic device that uses an elec second. The raster mechanism works by having magnetic coils
tron beam to produce a visible trace on a coated screen. IS At the instead of deflection plates (for greater control) direct the elec
narrow end of the CRT is an electron gun capable of generating tron beam to sweep horizontally across the screen for a prede
a continuous stream of electrons (Fig. 3-24). The electron beam termined number of vertical divisions approaching 256 or more.
passes through a pair of horizontal and vertical deflecting As the beam sweeps from left to right, the computer controls
plates. By changing the potential difference between the hori whether the beam is off or on. When the beam is on, the screen
zontal plates the electron beam is directed horizontally. Similar lights up. Each point of horizontal resolution may be on or off.
changes in potential on the vertical deflecting plates direct the The horizontal on or off points of resolution are sequentially ac
electron beam vertically. Simultaneously altering the potential tivated from left to right. The CRT trace is then immediately
on both sets of plates causes the electron beam to move in any brought back to the left-hand side of the screen and displaced
direction to light up the CRT's screen. The screen is coated with somewhat inferior to the next horizontal row of resolution
phosphor, which absorbs the energy from the electrons and points repeating the process. This continuous left/right and
converts it into visible light. The glow of the phosphor screen top/bottom movement traces out the memorized digital wave
persists for some time after the electrons have passed, allowing form contained in the computer's memory for the 256 or more
one to observe the beam's path. An electronic circuit connected rows. When the bottom right-hand comer of the CRT screen is
to the horizontal deflection plates causes the electron beam to reached, the entire process begins again. In short, rastering re
repetitively sweep across the screen at rates (sweep speeds) de generates the digital representation of the analog signal stored
termined by the operator. in the instrument's memory repeatedly over a very short period
of time so that the phosphor that signifies an "on" position is
ANALOG SIGNAL prevented from fading and allows the waveform to appear with
unvarying luminance. The waveform appears "frozen" on the
The original electrodiagnostic instruments used an analog or CRT screen so that the investigator can analyze any portion of
real-time signal to drive the vertical deflection plates, thereby the waveform without causing undue discomfort to the patient.
describing a voltage change over the screen's time input by the
practitioner. For observing MUAPs in needle electromyogra TRIGGER AND DELAY LINE
phy, a free-running or continuous sweep was used. When per
forming nerve conduction studies, the current stimulator A method to present a continuously firing MUAP at the same
triggered the sweep to visualize the ensuing SNAP or CMAP. place on the CRT screen was developed to assist in morphologic
Multiple stimuli were necessary because the response would analysis during analog needle electromyographic examinations.
only persist for the duration of the phosphor. The convenience Although this was a real-time signal and required the patient to
of storing or "freezing" a trace on the screen to leisurely exam continuously activate the same MUAP over time, it essentially
ine its fine details was not available. "froze" the potential on the CRT so that it could be investigated.
Some portion of the real-time MUAP, e.g., initial rise or peak
DIGITAL SIGNAL amplitude, triggered the CRT sweep to begin moving. The
signal was then fed into an electronic circuit to phase delay with
The technologic advance of AID conversion allowed the de minimal signal distortion and in a sense "run around" inside the
sired signal to be stored within the instrument's "memory." It instrument until the sweep was several divisions along the
screen. The delayed analog signal was then fed to the electron
Beam-forming mask beam so that the potential could be traced onto the screen, and
Accelerating anode
the investigator could determine the amount of delay and the
trigger criteria. The end result of this trigger and delay line was
to delay or place the repetitively triggered waveform at the same
place on the CRT's screen so that it could be studied easily.
Currently available instruments can digitally store a signifi
cant portion of an analog signal and retrieve selected portions of
this time span. Once the desired MUAP has triggered the CRT's
sweep, the instrument's computer can select a chosen time
period preceding and following the region surrounding the trig
gered potential. The instrument then presents this information
and continually updates the screen to monitor any changes in
the potential. Because the potential is in the instrument's
memory through analog to digital conversion, it can be "frozen"
on the CRT at any time. When this is accomplished, the instru
Figure 3-24. A cathode ray tube (CRT). The electron beam ment continually replenishes the chosen time period so rapidly
sweeps across the screen at regular rates by the horizontal deflection that to the human eye it appears to be stationary. With respect to
plates while the vertical deflection plates describes the waveform de the trigger and delay line, the patient is still required to continu
tected by the instrument. (Modified from Diamond SR: Fundamental ally activate the muscle under investigation. If voluntary activa
Concepts of Modern Physics. New York, AMSCO School Publications, tion ceases, the last stored potential usually remains on the
1970.) screen.
Chapter 1 INSTRUMENTATION - 91
~~
STIMULATOR TYPES
Two basic types of stimulators are commercially available:
constant-voltage and constant-current. The duration over which
a stimulus is delivered can usually be varied between 0.05 ms
and 1.0 ms. The usual standard practice in exciting peripheral
nervous tissue is to use a suprathresbold excitation, Le., a cur
Figure 3-25. Neural stimulation. A stimulator's cathode (-) and rent or voltage intensity 1(}-20% above that sufficient to depo
anode (+) are placed on the skin overlying an unmyelinated nerve. A, larize the entire nerve. This can be determined by observing the
Small amounts of current are delivered insufficient to activate the amount of stimulus required to produce an evoked nerve or
nerve. B,A larger stimulus is presented to the nerve which causes it to musc1e response that no longer increases despite more current,
depolarize.A capacitive current hyperpolarizes the neural tissue under and then providing an additional 10-20% more current. As pre
the anode while depolarization occurs about the cathode. (Modified viously stated, an impedance is always present between the
from Brown WF: The Physiological and Technical Basis of Electro stimulator's surface and the tissue to be activated. Additionally,
myography. Boston, Butterworth-Heinemann, 1984.) this impedance can vary during the course of the investigation
92 - PART I FUNDAMENTAL PRINCIPLES
or between multiple stimuli at the same site. Ohm's law, E::: I x nerve may be impaled by the needle, which apparently does not
Z, can be used to appreciate the characteristics of the two cate result in long-term sequelae. Signs and symptoms suggesting
gories of stimulators. If the impedance (Z) varies between suc nerve penetrations include paresthesias in the nerve's sensory
cessive stimuli and a constant current stimulator delivers the area, deep aching pain in muscles innervated by the nerve,
same amount of current (I) during each impulse, then the volt muscle fasciculations, and less than 1.0 rnA required to excite
age (E) output must vary. If the intervening tissue's impedance the nerve. 5 The site of stimulation is well defined by the loca
between the cathode and nerve increases or decreases, the volt tion of the needle's tip. The anode's placement should be at least
age necessary to drive the same amount of current into the body several centimeters away from the cathode and can be on the
for each impulse must also increase and decrease, respectively. skin's surface or subcutaneous. One should not use a standard
For example, a constant-current stimulator placed on the skin concentric or bipolar needle electrode to deliver a depolarizing
with a total electrode-to-nerve impedance of S,OOO 0 set to de current because of the danger of increased current densities
liver 20 milliamperes (0.02 amperes {A}) for every impulse will about the rather small cathode surface. The stimulating surface
require 100 V to drive this current into the body (E = I x Z = area of these two electrodes cannot be increased as they are
0.02 A x S,OOO 0 = 100 V). Should the impedance decrease to fixed by the manufacturer.
2,SOO 0 after several stimuli, 20 rnA will continue to be deliv When using a surface stimulator, the size of the cathode and
ered, but the voltage required for this amount of current is now anode have been suggested to be at least 3-S mm in diameter to
SOY. avoid concentrating the current density about the skin and pro
A constant-voltage stimulator emits the same voltage for each ducing pain in the patient. s It is also possible that the site of
stimulation, but may vary the amount of current required if the neural excitation does not exactly correspond to the presumed
impedance between the electrode and excitable tissue changes. site of skin cathode placement. The nerve may lie relatively
If 100 V are necessary to excite a nerve with a cathode-to-anode deep to the cathode or take an unexpected course requiring large
impedance of 10,000 0, then lOrnA is the necessary current for stimulus intensities. An increase in the stimulation's intensity or
nerve excitation. However, if the impedance increases to IO,SOO duration may cause the actual site of depolarization to spread
0, the instrument will deliver 9.S rnA for a constant 100 V stim some distance from the cathode (see Chapter 2). There are ad
ulation. Both the constant-current and constant-voltage stimula vantages and disadvantages to both surface and near-nerve
tor are adequate for routine purposes. If it becomes necessary to needle stimulation techniques (Table 3-4). It is advisable for the
quantify the amount of current delivered for a particular investi clinician to become familiar with both types of stimulation
gation, e.g., SSEp48 or facial nerve stimulation, 19 a constant-cur methods and to recognize when they are clinically appropriate.
rent device is preferred. Constant-current stimulators also may
produce less stimulus artifact (see below) than a constant-volt STIMULATOR PLACEMENT ERRORS
age stimulator. 5
Close inspection of most but not all commercially available
SURFACE VS. NEEDLE EXCITATION surface stimulator devices reveals that the cathode (black) and
anode (red) are color-coded. Additionally, a minus (-) and plus
It is possible to stimulate excitable tissues with any of the fol (+) sign are located near the cathode and anode, respectively.
lowing cathode/anode combinations: (1) cathode/anode on the During an examination, it is possible to unknowingly reverse
skin's surface, (2) monopolar near-nerve needle cathode placed the location of the cathode and anode at one or possibly more
in close proximity to the nerve and a somewhat distant com stimulation sites, resulting in potentially erroneous diagnostic
pletely bare (to spread out the current) subcutaneous anode, and conclusions. IS To illustrate this possible source of error, let us
(3) monopolar near-nerve needle cathode and a surface anode. first correctly stimulate the median nerve at the wrist 8 cm prox
Either a constant-current or constant-voltage stimulator can be imal to the abductor pollicis brevis muscle's motor point, and
used with any of the above three techniques. The first type of again at the antecubital fossa 23 cm proximal to the previous
cathode/anode combination (surface stimulation) has already excitation site. The distal and proximal latencies to the CMAP
been discussed above and is widely used because of conve
nience. A near-nerve needle cathode also can be used. Most op
Table 3-4. Surface VI. Near-Nerve Needle Stimulation··44
erators use needle cathodes because a particular nerve may be
located deep within the body and not be readily accessible (e.g., Advantage Disadvantage
spinal nerve roots) to a surface stimulator or when surface stim Surface
ulation requires excessive amounts of current to excite a nerve No need to puncture skin Uncertainty about excitation site
and subsequently causes patient discomfort. The near-nerve Time efficient Excitation requires more currentl
cathode requires a low current (voltage) intensity because the voltage to excite nerve than near·
depolarizing current density associated with the needle's tip is nerve needle and may be relatively
located next to the nerve to be excited. Less current also pro more painful
duces relatively little discomfort to the patient provided they do
Near-Nerve Needle
not mind the initial needle insertion. A needle or surface anode
Excitation of deep-lying May take more time
can be used with similar results.
nerves
Caution has been expressed regarding too high a current den
sity accumulating about the stimulating needle's tip and poten Less current density! Can pierce nerve
less pain
tially injuring the nerve. Peeling the Teflon back from a
More exact location of May scare patients
monopolar needle decreases the current density and possibly
protects the nerve from damage. 53 Also, a stimulus duration of nerve excitation (less
stimulus spread)
O.OS ms without removing the Teflon has been recommended
when using a near-nerve needle as a cathode. 44,60 Occasionally a Less stimulus artifact Possibly more expensive
Chapter 3 INSTRUMENTATION - 93
are noted to be 3.1 and 7.1 ms, respectively.18 The clinically cal us first consider the upper-limb SEP with a 50 ms analysis
culated nerve conduction velocity (NCV) over the 23-cm seg time. If the entire waveform requires at least 50 ms (latency of
ment of nerve is 58 mls (NCV = distance/time 230 mml(7.1 action potential to cortex + potential's duration =CRT screen's
ms 3.1 ms) = 58 mls). The cathode and anode are separated by analysis time: 50 ms) to be resolved, it can be thought of as re
a distance of 2.5 cm, which means that it will take the nerve's curring once every 50 ms for a frequency of 20 Hz (1/50 ms x
action potential 0.4 ms to travel this distance (58 mls =25 mmlt; looo ms/l sec = 20 Hz). If the entire screen/potential repre
t = 0.4 ms). sents 50 ms of analysis, a stimulus frequency greater than 20
If the median nerve is inadvertently excited at the wrist with Hz means that two stimuli will be given during one CRT
the stimulator's cathode and anode reversed, the distal motor la sweep. As a result, 20 Hz is the stimulus frequency's upper
tency is now 3.5 ms. The CMAP's time of onset (3.5 ms) is pro limit. Two stimuli delivered during one sweep may cause wave
longed compared to the previous value because the cathode is form distortions because the two waveforms will overlap with
no longer 8.0 cm but 10.5 cm (8.0 cm + 2.5 cm) proximal to the ensuing phase addition or cancellation. In the lower limb, the
muscle because of the added distance of the cathode/anode sep stimulation frequency's maximum is 10 Hz (11100 ms x 1000
aration. It will take 0.4 ms longer for the action potential to ms/l sec 10Hz). Although the stimulus rate upper limits
reach the muscle with the cathode and anode reversed distally. have been derived from a purely instrumentatal standpoint, ad
Stimulating the nerve correctly at the elbow now yields an inter ditional physiologic factors within the nervous system may re
stimulus time of3.6ms (7.1 ms-3.5 ms) for an NCV of 64 mls. quire lower stimulus rates « 5-7 Hz) to avoid waveform
The distal stimulation error resulted in a 6 mls elevation above distortion (see Chapter 9).48
the true conduction velocity. Reversing the cathode/anode ori
entation proximally but not distally produces a prolonged STIMULUS ARTIFACT
elbow-to-muscle latency of 7.5 ms (7.1 ms + 0.4 ms). The NCV
calculated with a proximal stimulus error is 52 mls or 6 mls less When performing peripheral nerve stimulation studies, the
than the true NCV. A consistent error of reversing the beginning of the CRT trace is typically disturbed by a relatively
cathode/anode relationship both distally and proximally cancels large potential decreasing toward the baseline from either the
the error and the correct NCV of 58 mls is obtained (NCV = positive or negative direction. This potential results from the
230/{7.1 ms + 0.4 ms} {3.1 ms + 0.4 ms} = 58 mls). The stray currents of the stimulator, or stimulus artifact, being
distal motor latency, however, remains erroneously prolonged. recorded by the instrument. Occasionally, this potential may in
This example clearly demonstrates that inadvertent reversal of terfere with the desired response as its decrementing phase co
the cathode and anode can increase or lower a nerve's NCV. If a incides with the investigated potential's onset or peak latency. It
patient has a normal NCV, it is possible to reduce it into the ab is important to know how to minimize the occurrence and detri
normal range. Likewise, an abnormally slow NCV can be ele mental effects of stimulus artifacts.
vated into the normal range, causing the investigator to overlook The stimulus artifact is nothing more than the current/volt
a disease state. The distal motor latency, although prolonged by age delivered from the stimulator's electrodes taking paths of
distal cathode/anode reversal, may lead to the same potential least resistance through the extracellular fluid and being de
errors as for NCV. tected by the recording electrodes. It precedes the action poten
tial because neural conduction is considerably slower than the
STIMULUS FREQUENCY volume-conducted stimulus artifact. Also, the stimulator effec
tively acts as a dipole current source, thus generating a far-field
The optimal rate at which a stimulus is delivered to evoke a potential (see Chapter 2) which extends instantaneously
particular response may need to be considered, particularly if throughout the body and is detected immediately by the record
the waveform has a long acquisition time. A potential may re ing electrodes. Although the stimulator is electrically isolated
quire a relatively long time to be resolved because it may have a from the instrument and its ground, a stimulus artifact is still de
long duration, arise from a polysynaptic pathway (blink reflex), tected. The phrase isolated from ground means that a stimulat
traverse the peripheral nervous system twice (F-wave; H ing pulse is generated in the stimulator through a transformer
reflex), or the site of stimulation may be far from the recording that does not require physical contact through wires but uses an
electrode location. An example of a potential that arises from electromagnetic field. An absence of physical contact within the
some of these conditions is the somatosensory evoked potential instrument reduces a portion of the artifact from being detected
in which a nerve is excited at the wrist or ankle and one set of through the instrument's wiring and limits its observation to the
recording electrodes is located on the scalp. As you might antic current effects within the body.
ipate, it will take a relatively long time for the induced action The investigator may have to effect several possible changes
potential at the wrist and ankle to reach the somatosensory at the (1) stimulus site, (2) intervening tissue between the stimu
cortex. The lower-extremity waveform may take approximately lus location and recording electrodes. and (3) at the recording
40 ms while the upper-extremity potential requires 22 ms to electrodes if the stimu1us artifact interferes with the observed
result in waveforms recorded at the brain. In pathologic condi potential (Table 3-5). The stimulator's anode can be rotated
tions these latencies can be considerably longer. Additionally, about the cathode in small increments in either the clockwise or
evoked potentials contain mostly low frequencies and as a result counter-clockwise direction until the artifact is minimized. 37
are long-duration potentials. The complete waveform may be 20 This can significantly reduce the stimulus artifact because the
ms or greater in duration. A total analysis time of 50 ms and 100 isopotentiallines between the cathode and anode are preferen
ms are usually recommended for upper- and lower-limb SEPs, tially aligned by rotation so that similar lines of potential or
respectively. near-zero potentials originating from the stimulator are placed
Given the extended analysis time required to completely re on the two recording electrodes (Fig. 3-26). Similar data pre
solve the entire SEP waveform compared to SNAPs and CMAPs, senting to the differential amplifiers will be eliminated as a
the stimulus frequency becomes an important consideration. Let common mode signal. If the stimulus artifact is large, dissimilar
94 - PART I FUNDAMENTAL PRINCIPLES
Table 3-S. Stimulus Artifact Reduction paths of current flow. Wiping the skin thoroughly with alcohol
Remove perspiration circumferentially around limb between often can prevent the stimulus artifact from preferentially trav
stimulator and recording electrodes eling over the skin to reach the recording site. The impedance
beneath the stimulating and recording electrodes should be re
Reduce impedance between skin and recording/stimulating
duced (gently abrading the skin, cleaning electrodes) so that
electrodes
both electrodes record as nearly the same signal from the stimu
Use minimal amounts of electrolyte paste lator as possible to assist in common mode rejection.
Avoid electrolyte paste between cathode and anode Remember that differences between the two recording elec
Remove all body lotion and makeup between stimulator and trodes are amplified. If there is a marked disparity of impedance
recording electrodes for E-! and E-2, the electrodes record slightly different signals
from the stimulator that will be amplified instead of rejected.
Place ground electrode between stimulator and recording
Recording electrode leads should be kept as short as possible. A
electrodes
large ground electrode placed adjacent to the E-l recording
Use just supramaximal stimulus electrode between it and the stimulator will help dampen the
Rotate anode about cathode stimulus artifact. Crossing the stimulator's cable with that of the
Use a needle cathode to approach stimulus site amplifier or electrode leads must be avoided in order to mini
mize artifacts. The stimulus artifact is a slowly changing, low
Try constant-current as opposed to constant-voltage stimulus frequency potential that can be reduced by elevating the
low-frequency filter slightly. It is important not to increase the
high-pass (low frequency) filter too much because it can distort
lines of potential extending out into the body from the cathode the signal of interest. Any or all of the above techniques can
and anode are recorded and amplified instead of being reduced help alleviate excessive stimulus artifact.
through common mode rejection. As Iowa stimulus intensity as If the above methods fail to sufficiently reduce the stimulus
possible should be used to evoke a maximal potential. One artifact, one should be aware of potential latency effects result
should also locate the cathode as close to the nerve as possible ing from superimposition of electrophysiologic waveforms and
and near-nerve needles can help reduce annoying artifacts. the artifact. 53 A negative stimulus artifact (above the baseline)
Unnecessarily large stimulus voltages can overwhelm the am decaying toward the baseline while a potential's negative phase
plifiers and prevent the nerve or muscle response from being is still rising will result in the onset latency shifting artifactually
observed. The distance between the stimulating and recording to the left, i.e., shortened. The rising phase of the waveform can
electrodes should be as large as possible to still record the de cels the descending phase of the artifact thereby decreasing the
sired signal. An increased distance allows the stimulus artifact onset latency. A negatively decaying stimulus artifact coincid
enough time to settle back to baseline before the neural impulse ing with a potential's peak shifts the peak's latency to a shorter
reaches the recording electrodes' location and evokes a re value. The declining negative aspect of the artifact cancels the
sponse. Perspiration and electrolyte gel must be removed from initial rising negative portion of the waveform, resulting in a po
the skin separating the various electrodes to eliminate aberrant tential that occurs artifactually earlier in time. On the other
hand, if the negative stimulus artifact is increasing coinciden
tally with the potential's negative peak, the entire potential
shifts to the right, increasing the onset and peak latency. Of
course, the stimulus artifact also can originate below the base
line (positive direction) and interfere with waveform recordings.
A stimulus artifact below but decaying toward the baseline can
overlap with a negative spike potential and prolong the peak la
tency. If the artifact is below the baseline but moving away from
it when a potential is rising, phase cancellation effects will
shorten the onset latency. A waveform's peak occurring with a
positively sloping stimulus artifact shortens the peak latency.
INTERFERENCE
The environment in which most electrodiagnostic examina
tions are performed contains substantial amounts of electrical
interference or noise. For our purposes we may define interfer
Figure 3-26. Anodal Rotation. An antidromic median SNAP is ence as any signal that can contaminate the desired potential
recorded with the cathode (Ca) located 7 cm from the active record whether it originates internally from the patient (biologic/artifi
ing electrode (Ac) with the reference electrode (R) located 4 cm distal cial) or some external source. A number of patient-generated
to the active electrode. The anode (Ani) is 2.5 cm proximal to the noises or artifacts can interfere with the waveform under inves
cathode. Trace A reveals the SNAP with an ill-defined onset latency, as tigation; it is helpful for the investigator to recognize them so
it is clearly affected by the stimulus artifact. Rotating the anode about that appropriate solutions can be found to reduce them. One of
the cathode in 0.5 cm increments (An2-An4) eventually results in sup the more common noises observed is movement artifact, which
pression of that portion of the stimulus artifact that interferes with can occur in two primary forms. If surface electrodes are used,
the SNAP's onset, thus permitting measurement of the parameter the patient can unintentionally cause the recording electrodes to
(traces 8-0). shift positions slightly. This movement can cause the skin to
Chapter 3 INSTRUMENTATION - 95
alter its shape creating a voltage difference between the skin and interference problems. When the source of environmental noise
electrode metal (electrode potential) with some frequency com remains unknown, one can connect the active and reference am
ponent. If this discharge has a frequency greater than the filters' plifier ports with a jumper cable and use this as an antenna to
bandwidth, a signal may be created and the potential thus inter search out the directional characteristics of the noise and try to
feres with the desired biologic response. Firmly securing the define its source. Environmental noise often can be eliminated
electrode can help reduce this problem. A second common by surrounding the examination room completely with copper
movement artifact is incomplete relaxation of muscles in close wire, forming the so-called Faraday's box. This is a rather ex
proximity to the recording electrode. The recorded MUAPs can pensive venture and can be totally defeated by not using an iso
overlap with the waveform under investigation and obliterate lated earth ground, i.e., grounding the copper shielding to a
the response. It is also possible for regularly firing MUAPs to different ground from that used by other instruments in the
be mistaken for the desired response, particularly when the true building. A simple and effective method to reduce environmen
response is pathologically absent. Turning the volume up on the tal noise is to ground the electric outlet to an isolated earth
speaker may help identify the contaminating MUAPs and the ground spike. It is also important to plug the instrument into a
patient can be instructed to relax. When performing needle elec dedicated circuit. This is an electric circuit coming straight
tromyographic examinations on muscles about the thorax, e.g., from the outside power line into your office that is used only to
pectoralis and serratus anterior muscles, a regularly recurring power the instrument. These two relatively simple procedures
waveform of rather large amplitude occasionally can be ob should take care of most environmental artifacts.
served to impede MUAP observation. This is merely the EeG
and can be ignored as it rarely poses a significant inconve
nience. Similarly, a regularly recurring spike potential indicates ELECTRICAL SAFETY
that the patient most likely has a cardiac pacemaker.
Interference arising outside of the patient is frequently ob The clinician must realize that all electrical devices leak some
served when high amplifier gains are used. The most common current to the instrument's chassis and electrodes. Although the
source of environmental interference is the 6O-Hz noise. It may manufacturer must ensure that their instruments leak minimal
be recognized by a complete cycle (peak-to-peak time interval) currents, the operator has the responsibility of ensuring periodic
every 16.7 ms (60 cycles/WOO ms 1 cyc1e/16.7 ms). The electrical safety checks of both the electrophysiologic device
sudden appearance of 6O-Hz interference during the course of and laboratory by qualified personnel. A failure of the instru
an examination should raise the possibility that an electrode has ment's safeguards with respect to electrical safety can lead to
become disconnected either from the patient or instrument (Fig. large and potentially dangerous current flows into the patient. If
3-27). It is also possible that an electrode lead has failed. An im a patient comes in contact with a metal bed or other electrical
pedance mismatch between the two electrodes can reduce instrument, a faulty ground plug can allow current to flow into
common mode rejection causing a smooth undulating sine the patient through the amplifier's ground lead. The maximum
wave. Reducing the impedance of the electrode or using the acceptable leakage current from a chassis to ground is 100 J.l,A
same type of electrode can diminish these artifacts. A rather and from the patient's input leads to ground is 50 J.l,A.S3 The fre
characteristic alternating positive/negative spike pattern of fluo quencies of current to be concerned about range from 0 to 1,000
rescent lighting also is commonly seen (Fig. 3-27). If there are Hz because they are capable of exciting nerve and muscle
no problems with the electrodes, using a simple incandescent tissue. Electrically sensitive patients (having intravenous or
light bulb with a table lamp allows one to tum off the fluores other lines that may lead to the heart, such as arterial lines or
cent lights. Also, it is possible to purchase fluorescent lights catheters) should not be exposed to more than 10 J.lA ofleakage
with low-noise condensers and this may help eliminate any current. Electrical stimulation of peripheral nerves should be
A 0
~
J20
5m.s
IN J5000I1V
IOms
Figure 3-27. Common forms of Interference observed
B E
on a CRT screen. A. Fluorescent light during an electromyo
graphic examination. B. Pure fluorescent light interference reveal ~
ing details of its usual alternating spike appearance. C,
Combination of fluorescent light and 60-Hz interference. D. J5000Jl.V
Almost pure 60-cycle interference. E. Same trace as that in 0 IOms
except a 600Hz notch filter has been introduced into the record c
ing system.
96 - PART I FUNDAMENTAL PRINCIPLES
performed away from the thorax in patients with cardiac pace 14. Cooper R: Electrodes. Am J EEG Tech 1963;3:91-101.
15. Diamond SR: Fundamental Concepts of Modem Physics. New York, AMSCO
makers. Also, prior to stimulating electrically sensitive patients, School Publications, 1970.
one should thoroughly dry the skin of any perspiration to avoid 16. Dorfman LJ, McGill KC. Cummins KL: Electrical properties of commercial con
conducting any current to the electrically sensitive area. centric EMG electrodes. Muscle Nerve 1985;8:1-8.
A few relatively simple safety measures should be employed 17. Dreyer SJ, Dumitru DD, King JC: Anodal block versus anodal stimulation: Fact
or fiction. Am J Phys Med Rehabi11993;72:10-18.
to ensure optimal patient safety: 18. Dumilru D, Walsh NE: Practical instrumentation and common sources of error.
I. It is necessary to have the device routinely inspected by Am 1 Phys Med RehabilI988;67:55-65.
qualified personnel familiar with measuring current leakage and 19. Dumitru 0, Walsh NE, Porter LD: Electropbysiologic evaluation of the facial
nerve in Bell's palsy. Am J Phys Med Rehabil 1988;67:137-144.
defective electrical instruments. 20. Dumitru D, Walsh NE: Electrophysiologic instrumentation. In Dumitru 0 (ed):
2. The electrical outlet into which the instrument is con Clinical Electrophysiology: Physical Medicine and Rehabilitation State of the
nected also should be checked for electrical safety. Art Reviews. Philadelphia, Hanley & Belfus, 1989.
3. In order to avoid power surges, the device should be 21. Dumitru D, Lester J: Comparison of SEP surface and needle electrodes. Arch
Phys Med Rehabil 1991 ;72:989-992.
turned on or off, respectively, prior to attaching and after remov 22. Dumitru D, King JC, Nandedkar SD: Motor unit action potentials recorded with
ing electrodes. concentric electrodes: Physiologic implications. Electroencephalogr Clin Neuro
4. Avoid using extension cords, as they may increase leakage physiol 1997;105:333-339.
23. Dumitru D, King JC, Nandedkar SD: Concentric/monopolar needle electrode
currents.5 3 modeling: Spatial recording territory and physiologic implications. Electro
5. All electrical devices that are to be attached to the patient encephalogr Clin Neurophysiol 1997;105:370-378.
must be plugged into the same outlet to share a common ground. 24. Dumitru D, King lC, Nandedkar SO: Comparison of single-fiber and macro elec
6. Attach only one ground to a patient during the examination. trode recordings: Relationship to motor unit action potential duration. Muscle
Nerve 1997;20: 1382-1388.
Close attention to technical details will ensure the safe acqui 25. Dumitru D. King JC, Nandedkar SD: Concentric and single fiber electrode spa
sition of data with minimal risks to the patient. tial recording characteristics. Muscle Nerve 1997;20: 1525-1533.
26. Dumitru D, King lC: Concentric needle recording characteristics related to depth
of tissue penetration. Electroencephalogr Clin Neurophysiol 1998; J09: 124-134.
27. Pleasel AF, Tuck RR: Variability of repeated nerve conduction studies. Electro
CONCLUSION encephalogr Clin Neurophysiol 1991 ;81 :417-420.
28. Gitter AJ, Stolov WC: AAEM minimonograph #16: Instrumentation and mea
An important but frequently overlooked aspect of the electro surement in electrodiagnostic medicine-part II. Muscle Nerve 1995;18:
812-824.
diagnostic medicine examination is the practitioner's under 29. Guld C: On the influence of the measuring electrodes on duration and amplitude
standing of the instrument. This is unfortunate because a faulty of muscle action potentials. Acta Physiol Scand 195 I ;25(Suppl 89}:30-32.
comprehension of how the instrument modifies biologic signals 30. Howard JE, McGill KC, Dorfman LJ: Properties of motor unit action potentials
recorded with concentric and monopolar needle electrodes. Muscle Nerve
certainly can result in significant distortions of the acquired 1988;11:1051-1055.
data. Distorted waveforms can readily lead to a misinterpreta 31. Jasper H, Ballem G: Unipolar electromyogram of nonnal and denervated human
tion of the data and lead to a false positive or negative diagnosis. muscle. 1 Neurophysiol 1949; 12:231-244.
A diligent attempt to understand the material presented in this 32. Johnson EW: The EMG examination. In Johnson EW (ed): Practical
Electromyography, 2nd ed. Baltimore, Williams & Wilkins, 1988.
chapter should provide the practitioner with sufficient informa 33. Karam DB: AIDS and the electromyographer. Arch Phys Med Rehabil
tion to avoid many potential instrumentation errors. 1986;67 :491.
34. Kimura 1: Electrodiagnosis in Diseases of Nerve and Muscle: Principles and
Practice. Philadelphia, F.A. Davis, 1983.
REFERENCES 35. King JC, Dumitru D. Stegeman D: Monopolar needle electrode spatial recording
characteristics. Muscle Nerve 1996; 19: 1310-1319.
1. Adrian ED, Bronk DV: Discharge of impulses in motor nerve fibers. 1 Physiol 36. Kohara N, Kaji R, Kimura J: Comparison of recording characteristics of mono
1929;67:119-151. polar and concentric needle electrodes. Electroencephalogr Clin Neurophysiol
2. Barkhaus PE, Nandedkar SD: Recording characteristics of the surface EMG 1993;89:242-246.
electrodes, Muscle Nerve 1994;17:1317-1323. 37. Komfield MJ, Cerra 1, Simons DG: Stimulus artifact reduction in nerve conduc
3. Barohn RJ, Jackson CE, Adams KK, Gronseth GS: An electrophysiologic com tion. Arch Phys Med Rehabil 1985;66:232-235.
parison of stainless steel and adhesive recording electrodes for nerve conduction 38. Kosarov D. Gydikov A: The influence of the volume conduction on the shape of
studies, Muscle Nerve 1995;18:1218-1219, the action potentials recorded by various types of needle electrodes in normal
4. Braddom RL: Somatosensory, brainstem, and visual evoked potentials. In human muscle. Electromyogr Clin NeurophysioI1975;15:319-335.
Johnson EW (ed): Practical Electromyography. Baltimore, Williams & Wilkins, 39. Lawler JC, Davis MJ. Everton CG: Electrical characteristics of the skin. J Invest
1988, pp 369-416. Denn 1960;34:301-308.
5. Brown WF: The Physiological and Technical Basis of Electromyography. 40. Misulis KE: Basic electronics for clinical neurophysiology. J Clin Neurophysiol
Boston, Butterworth Publishers, 1984. 1989;6:41-74.
6. Buchthal F, Guld C, Rosenfalck P: Action potential parameters in normal human 41. Nandedkar SD, Sanders DB, Stalberg EV, Andreassen S: Simulation of concen
muscle and their dependence on physical variables. Acta Physiol Scand 1954;32: tric needle EMG motor unit action potentials. Muscle Nerve 1988;11: 151-159.
200-218. 42. Nandedkar SD, Dumitru D, King IC: Concentric needle electrode duration mea
7. Buchthal P, Rosenfalck P: Action potential parameters in different human mus surement and uptake area. Muscle Nerve J 997;20: 1225-1228.
cles. Acta Psychiatr Neurol Scand 1955;30:125-131. 43. Pease WS, Bowyer BL: Motor unit analysis: Comparison between concentric
8. Butler BP, Ball RD, Albers JW: Effect of electrode type and position on motor and monopolar electrodes. Am 1 Phys Med Rehabil 1988;67:2-6.
unit action potential configuration. Muscle Nerve 1982;5:S95-S97. 44. Pease WS, Fatehi MT, Johnson EW: Monopolar needle stimulation: Safety con
9. Chu J, Chan RC: Changes in motor unit potential parameters in monopolar siderations. Arch Phys Med Rehabil1989;70:412-414.
recordings related to filter settings of the EMG amplifier. Arch Phys Med 45. Pease WS, Pitzer NL: Electronic filter effects on nonnal motor and sensory nerve
RehabiI1985;66:60I-<i04. conduction tests. Am J Phys Med RehabilI990;69:28-31.
10. Chu J, Johnson RJ: Electrodiagnosis: An Anatomical and Clinical Approach. 46. Pollack V: The waveshape of action potentials recorded with different types of
Philadelphia, J.B. Lippincott, 1986. electromyographic needles. Med Bioi Eng 1971 ;9:657-664.
II. Chu J, Chan RC, Bruyninckx F: Progressive Teflon denudation of the monopolar 47. Reiner S, Rogoff lB: Instrumentation. In Johnson EW (cd): Practical Electro
needle: Effects on motor unit potential parameters. Arch Phys Med Rehabil myography. Baltimore, Williams & Wilkins, 1980.
1987:68:36-40. 48. Spehlmann R: Evoked Potential Primer. Stoneham, MA. Butterworth Publishers,
12. Chu 1, Chan RC, Bruyninckx F: Effects of the EMG amplifier filter settings on 1985.
the motor unit action potential parameters recorded with concentric and monopo 49. Stalherg EV, Trontelj J: Single Fiber Electromyography. Woking, UK. Mirvalle
lar needles. Electromyogr Clin Neurophysiol 1986;26:627-639. Press, 1979.
13. Cole JL: Equipment parameter determinants in evoked potential studies. Bull 50. Stalberg EV: Macro EMG: A new recording technique. J Neurol Neurosurg
Am Soc Clin Evoked Potentials 1984:3:3-11. Psychiatry 1980;43:475-482.
Chapter 3 INSTRUMENTATION - 97
51. Stalberg EV, Chu J, Bril V, et al: Automatic analysis of the EMG interference 58. Weber RJ, Piero D: Entrapment syndromes. In Johnson EW (ed): Practical
pattern. Electroenceph Clin NeurophysioI1983;56:672-681. Electromyography. Baltimore, Williams & Wilkins, 1980.
52. Stalberg EV: Personal communication. 59. Wee AS, Ashley RA: Relationship between the size of the recording electrodes
53. Stolov W: Instrumentation and measurement in electrodiagnosis. Mini and morphology of the compound muscle action potential. Electromyogr Clin
monograph #16, American Association of Electromyography and Electrodiag Neurophysioll990;30:165-168.
nos is, Rochester, MN, 1981. 60. Wongsam PE, Johnson EW, Weinerman JD: Carpal tunnel syndrome: Use of
54. Swain!D, Wilson GR, Crook SC: A simple method of measuring the electrical palmar stimulation of sensory fibers. Arch Phys Med Rehabil 1983;64:16
resistance of the skin. J Hand Surg 1985;IO-B:319-323. 19.
55. Thage 0, Trojaborg W, Buchthal F: Electromyographic findings in polyneuropa 61. Wiechers DO, Blood JR, Stow RW: EMG needle electrodes: Electrical imped
thy. Neurology 1963; 13:273-278. ance. Arch Phys Med Rehabil 1979;60:364-369.
56. Tjon-A-Tsien AML, Lemkes HHPJ, van der Kamp-Huyts AJC, van Dijk JG: 62. Wiechers DO: Single fiber electromyography. In Johnson EW (ed): Practical
Large electrodes improve nerve conduction repeatability in controls as well as in Electromyography, 2nd ed. Baltimore, Williams & Wilkins, 1988.
patients with diabetic neuropathy. Muscle Nerve 1996;19:689-695. 63. Zablow L, Goldenshohn ES: A comparison between scalp and needle electrodes
57. Van Dijk JG, Tjon-A-Tsien A, van der Kamp W: CMAP variability as a function for the EEG. Electroenceph Clin Neurophysiol 1969;26:530--533.
of electrode site and size. Muscle Nerve 1995;18:68-73.
Appendix
APPENDIX OUTLINE
Electronic Devices
Series Circuit
Alternating Current Switches • Diodes • Amplifiers • Differential Amplifiers •
Exercise 2 Inductors
Cathode RayTube • Digital Processors (Computers)
Ground Filters Conclusion
This primer is written to explain as intuitively as possible orbiting negative electrons. Electron is the Greek word for
electricity and the function of the circuit elements: capacitors, amber. The amount of attraction is called voltage or electrical
inductors, resistors, rectifiers, switches, and amplifiers. These potential. Objects that have this attraction possess charge that
circuit elements are concepts that help explain how and why may be positive or negative. Negative charge is the amount of
electronic devices and biologic organisms react as they do to negative electrons present that are not balanced by protons.
electrical influences. All electronic devices can be simplified to Positive charge is the amount of excess protons not balanced by
variations of these six circuit elements. A working knowledge electrons. Objects that have excess positive or negative charge
of these circuit elements can help one understand and anticipate are said to be electrically "charged." Since electrons move more
the electrical behavior of the body, filters, and electrophysio freely than protons, positive charge is usually due to a deficit of
logic instruments. electrons rather than a surplus of protons (Fig. 2).2 The concepts
Since the circuit elements are really mathematical concepts of charge and electrical potential are analogous to the more
that help us understand how biologic and other real-life systems readily appreciated concepts of mass and gravitational poten
respond electrically, occasionally mathematical expressions are tial. An object with mass in earth's gravitational field are at
used. These cannot be read in the usual scanning fashion. tracted from a higher (gravitational potential) to a lower
Mathematical expressions are written in tightly compacted sym position (Fig. 3). The greater the mass (in kilograms), the
bolism and each symbol must be read as a word with each equa greater the force of attraction (in Newtons) to the earth.
tion read as a complete sentence. Exercises are provided to help Similarly, an object with a property called positive charge tends
one appreciate the usefulness of the mathematical expressions to move from a higher to lower electrical potential. I Oppositely,
in sol ving basic electrical problems. These exercises, once an object with negative charge tends to move from a lower
worked through, will also help one to more fully understand the (more negative) potential to a higher (more positive) potential.
concepts discussed as tools to be applied to electrophysiologic The greater the magnitude of the charge, the greater the magni
phenomena. tude of force, or voltage, of attraction.
The nylon comb being pulled through dry hair results in re
moving electrons from the comb's atoms, and the comb be
ELEMENTAL FORCES comes positively charged (Fig. 1). When small objects, with
their atoms and their mobile electron clouds, are brought near,
Ancient Greeks found that by rubbing amber with a woolen the objects' electrons are attracted to the comb's excess positive
cloth, small objects such as bits of paper would be attracted to charges and migrate to occupy more of that side of those atoms.
the amber. This effect can also be seen in passing a nylon comb This results in the small objects' atoms becoming relatively p0
through dry hair (Fig. 1) that is subsequently attracted to the larized, i.e., with a more negative side near the positively
comb. This phenomenon is called electrostatic attraction. I The charged comb, leaving the more positive side of the atoms far
cause of electrostatic attraction relates to the basic structure of ther away from the comb. This electrostatic attraction is in
atoms and an elemental force of attraction between two sub versely related to the distance separating the charges {Le., the
atomic particles. Positive protons in the center of an atom attract amber or comb will pick up paper from nearby but not from far
98
Appendix BASIC ELECTRICITY PRIMER - 99
away). The more negative side of the paper is closer and thereby +
more attracted to the comb than the more distant positive side is
repulsed, and so the uncharged paper clings. When combing wet
hair, the electrons removed flow back to the comb through the
conductive water and the comb does not become charged.
Likewise, if the charged comb is connected to the earth, e.g.,
dipping it into water in a sink, the excess charges are dispersed
leaving essentially no charge and subsequently the paper bits
will not cling. This charge dissipation is commonly experienced
when one walks on a nylon carpet on a dry day and touches a
light switch plate. The excess electrons, mechanically removed
from the carpet by one's shoes, conduct through the body to the Electrostatic
earth. The crackle and spark are the result of these electrons
"discharging" to the plate. Similar build-up of charges on a
more massive scale occurs in the development of thunder clouds
~ ....
:.£)·0::
'" ., 0
~
/
,.~,
_..........., ,
B
nano (to-I2).
I /".,,-,' \
(i ((:19 ~ \ )
RESISTANCE
The coulomb of positive charge isolated from the coulomb of
negative charge above have an electric field of attraction between 11 Eledrons (·11 charges)
\\\-/11
\ '- '-..;:/
,'--_/
/
..........
10 Electrons
- /
( - 10 charges)
them that totals 1 volt. If a path is provided along which charges 11 Protons (+11 chalg8S) 11 Protons (+10 charges)
could move, the negative charges, excess electrons, would flow, o charge +1 charge
or conduct, to the positive charges, which are atoms deficient in
electrons. This charge flow, or current, would continue until both
locations became uncharged, or neutral. At that point, no voltage
of attraction would be present between the two neutrally charged
c D
locations. However, if the one coulomb of charge buildup was
progressively replaced as the charges left and the electrons arriv
ing at the positively charged area were removed as fast as they
arrived, the attraction, or voltage, between the two locations
would continue unchanged. This is what a battery does. It main
tains a constant voltage between two locations despite current
flow. This is similar to a water pump that maintains pressure or
push to keep water current flowing (Figs. 5 and 6).2 A voltage figure 2. Forming a positive ion. A, Schematic of a balanced
source, such as a battery, has a cathode that replaces the elec sodium ion.Valence electrons are the outer more easily mobile elec
trons and an anode that removes the electrons that have flown to trons. B, Sodium atom now shown missing an electron. C,A resulting
it. Since electrons have negative charge, positive current is con positively charged ion results. D,This ion is now electrically equivalent
sidered to flow in the opposite direction from the negative elec to 1 positive charge. (From Cromwell L,Arditti M.Weibell FJ, et al:
tron flow, i.e., from anode to cathode (Fig. 6). In biologic Medical Instrumentation For Health Care. Englewood Cliffs. NJ,
systems, both positive and negative charges are present and Prentice-Hall. 1976. with permission.)
100 - PART I FUNDAMENTAL PRINCIPLES
but having a larger cross-sectional area can more readily accom (symbolized as "R"). Written mathematically, this is I = EIR, or
modate greater charge flow. Such a pathway is said to have less =
rewritten: E IR, which is called Ohm's law. 2 This simple
resistance to current flow. . equation becomes very useful in understanding how one should
Resistance is the description of how difficult it is for charge to expect certain circuits to behave, including those made by at
move through a certain path. This is analogous to the resistance taching an electrophysio!ogic instrument to a living body. The
to water flow caused by the pipes in a water circuit. A narrow units of resistance are ohms, symbolized as "n." Rewriting from
pipe resists the flow of water more than a wider pipe (Fig. 7). A Ohm's law: R == Ell, or 1 n = 1 VII A. Commonly used units of
very tight restriction in the water circuit may almost entirely de resistance include ill, which is 103 nand Mn, which is 1()6 n.
termine the amount of flow for a given pump pressure in a water Charges accumulate on the amber and woolen cloth since
circuit (i.e., the resistance of the rest of the pipe is relatively they do not allow easy movement of charges, and thus can hold
negligible compared to the constriction). Even this flow, how static charges more easily. They have very high resistance to
ever, can be increased by increasing the pump's pressure. Flow current flow and are called nonconductors or dielectrics.
can also be increased by opening the restriction (decreasing the Electrons are much more free to move in metals than in normal
resistance); thus, water flow is proportional to the pump pres saline, where sodium and chloride ions transports the charges.
sure, but inversely proportional to resistance. Similarly, electri Metal has very low resistance, and normal saline has higher re
cal current flow (symbolized as "I") is proportional to voltage sistance, although both are considered good conductors.
(symbolized as "E"), but inversely proportional to resistance Conductors can vary greatly in their resistance properties (Table
1). Often the resistance of metals, such as copper or aluminum
wire, is so much lower than that of the biologic materials that it
is considered negligible, or having essentially zero ohms (indi
cated by the straight lines in Fig. 6).2.6
Electrons EXERCISE I
deficiency
(positive Ions)
In Figure 6, the battery provides a constant voltage of 12 V
A B across the resistance which is 2 n. How much current flows?
P = Pump pressure
= ygh E = Voltage
= Potential = Electrical
to move potential
h water to move
current
+
+
P
t
Water
Answer: (Ohm's law) E = IR pole), the circuit is called a series circuit. Instead of the one re
12 V = I x 2 n; I = 12 VI2 n = 6A. Six amperes flow. sistor of Figure 6, two or more may be present (Fig. 8).
Each resistor adds to the circuit's overall resistance. Thus the
If the resistance is increased to 4 kn, how much current resistance (R) from the voltage source's anode to it's cathode, is
flows? RI + R 2; R = RI + R 2. Likewise, the current flow will be E = IR,
E = IR; 12 V = I x 4000 n; I = 0.003 A or 3 rnA. so E = I (R 1 + R2) and I = E/R; therefore, I = E/(RI + R2)'
Series circuits are useful because certain predictions can be
The voltage is now reduced to 4 m V; how much current made about the electrical potential occurring across each re
flows? sister in the circuit. Since by Ohm's law:
E = IR; 4 mV= 0.004 V = I x 4000 n. 1= E=IR,
therefore E = IR 1+ IR2 •
and
+
E R or
El = R RIR E
1+ 2
Thus, E} is proportional to E attenuated by a constant ratio of
R}/(R} + R 2).
~-------I This can be used as a voltage divider since R} and R} + R2
can be chosen to divide E into any portion desired, noting that
e- = actual direction charges R/(R 1 + R 2) is always 1 or less. For example, if R} = In and R2
(electrons) are flowing = 9n then RI + R2 = IOn and E} = (1/10) E or 1/10th ofE. This
Figure 6. Electrical current flow. The battery creates a "push," of concept is often used to control or attenuate the amount of volt
magnitude E, to move positive charges from its cathode (negative port) age applied, for instance across a speaker to control the volume
to its anode (positive port), which then flow down the electrical poten of sound produced (Fig. 9).
tial gradient back to the cathode by means of a resistor. Charge flow, or
current (I), is considered the direction of flow of positive charges. EXERCISE 2 (FIG. 10)
However, the charges that most easily flow through metallic wires are
electrons, which have negative charge. The electrons are actually moving
What is E2?
in the opposite direction to what is defined as positive current flow. Answer: Ez = (RzI{R} + R2})E; Ez = (2nJ{ln + 2n}) 9V = 6V.
R .. Orifice resistance A
P=Pump
W • Water flow
+
I
E
pressure
W=..E. or
A
~
(r
R1
+ +
A, .1!> }E'
E E =9V
R2
R2·211 }E2
Figure , O. Series circuit problem is shown with a battery of 9 V and
two resistors in series. What is the current (I) flowing in the circuit
Figure B. A series circuit is depicted (two resistors connected to and how much voltage drops across each resistor?
gether in series).
Varying
or
Voltage -
Speaker
Source
Figure II. Schematic for ground, or ground symbol. is depicted. This
point marks a common connection to the earth, which is usually as
Figure 9. Adjusting the voltage applied to a speaker by means of a sumed to be a relative zero potential.
variable resistor. potentiometer, is shown. As the potiometer's resis
tance increases, more of the applied voltage is dropped across this
larger resistor, the speaker resistance remaining constant, resulting in
reduced voltage across the speaker and a lower volume of sound pro
duced. The "volume" control knob on a radio is the potentiometer in
this circuit.
Appendix BASIC ELECTRICITY PRIMER - 103
Hl
+
+ E=9V
E=9V
2!l
F'pre 13. A parallel circuit (resistors have been connected to
gether in parallel) is shown.
Figure '2. The circuit of figure 10 with grounding shown. The point alternating electrical voltage to all appliances, lights, etc. (Fig.
marked with the ground symbol has now been conductively connected 14).
to the earth.
(lW{10+2n})9V =3 V.
What is ~ (which equals EI lrotal)?
Answer: =
II = ElRI 10 VIlO 0 IA =
=
12 =EIR2 IOVIlOO= 1 A
GROUND Ilotal = I] + 12 = 2A.
Positive charge
frltotal
Insulator
(air or thin
~
E= 10V
+
100
Negative charge
dielectric)
T
Symbol
+
water Storage Dam and Capacitance
E
i:l P - (water capacitance) x W Jl. VMfj- C xI
i:lt i:lt
Figure I B. The height of water behind a dam is proportional to the
potential gravitational energy of that water. The amount of water
Figure 16. Balanced bridge circuit. Unknown resistance, Rx, can be stored at any given water height reflects the capaCity of the reservoir
determined indirectly by adjusting the potentiometer, R"ot> so that Ev behind the dam. JUSt as with an electrical capacitor, the greater the
goes to zero voltage. At this point both parallel circuits represent amount of charge/water stored for a given potential electrical(volt
=
equal voltage dividers, thus Rx R"ot. The potentiometer's resistance is age)/gravitational(height) energy, the greater the capacitance/capacity.
often marked on its adjusting screw or the potentiometer can be re As charge/water is removed from the capacitor/reservoir, the poten
moved from the circuit and its impedance measured directly. tial electrical(voltage)/gravitational(height) energy decreases.
Appendix BASIC ELECTRICITY PRIMER - 105
R1 = 1 kn ; R2 = 2 kn or R2 = 1 kn
I
C 1 = O.1 ....F; C2 = O.1 ....F or C 2 = O.~F
to the lesser rate of charge flow. If the capacitor less readily ac Figure 2'. Current flow decay rates for different reSistor/capacitor
cepts charge (small capacitance), then the voltage across it pairs for the Figure 19 circuit. Note the product of the resistance and
builds up more quickly and the current stops sooner. A higher capacitance determine how fast the current approaches zero.
capacitance allows more charges to accumulate before its volt
age equals that of the voltage applied (similar to a large capacity without infinite current flow occurring. Thus capacitors can
reservoir accepting more water inflow before cresting the dam blunt or "filter" rapid voltage changes. For instance, given a
in Figure 18). How fast the capacitor charges is thus inversely square wave voltage source, the blunting of the rapid voltage
proportional to both Rand C. The value RC ='t, tau, is called changes of the square wave occur as shown in Figure 23.
the time constant of an R and C pair. The larger 't is, the longer The voltage change across a large capacitor for a given
time a given resistor and capacitor pair takes to charge or dis amount of charge shift is relatively small. At high frequencies
charge (Fig. 21 ).1 there is less time for charge movement, even with high currents.
Should the voltage source be replaced by a simple wire, the At high frequencies only small voltage shifts occur across a ca
charges on the capacitor will flow back through the R j and the pacitor despite possibly high alternating currents. This is similar
wire to the opposite plate where they are attracted, eventually to what occurs with a very small resistor. The capacitor's imped
neutralizing both sides and the voltage across the capacitor will ance (resistance of a capacitor to current flow) at high frequen
again return to zero resulting in zero current flow (Fig. 22). cies is low. Indeed, at an infinite frequency there would be no
Capacitors are useful because they can store energy.2 This time to move charge, thus no voltage change and the impedance
energy is actually stored in the electric field of mutual attraction of the capacitor would approach zero. At low frequencies (e.g., 0
between the charges on the separated foil plates. A defibrillator Hz or direct current) such as the battery/resistor/capacitor circuit
is an example of a clinical device that uses capacitor energy. A in Figure 19, once the capacitor is charged sufficiently to equal
selected amount of energy (in joules) is stored on a capacitor the battery's voltage, no current flows. Therefore, the capacitor's
that is connected to the defibrillator paddles through a push impedance approaches infinite resistance to current flow at 0 Hz.
button switch, which can be discharged through a patient At low frequencies, a capacitor has high impedance. Thus, ca
(equals R in Figure 22) at a relatively known rapid rate. 1 pacitor impedance varies inversely with frequency (Fig. 24). The
Since the capacitor's voltage depends on charge accumulation, =
frequency equivalent to Ohm's law is Vc IcZc' where Zc, the
the voltage across a capacitor cannot change instantaneously impedance of the capacitor, is a function of frequency.
I
I (mA)
9mA o
-9
o rnA 1.--_ _ _ _ _ _ _ _ __
a t = time
t = time
Figure 22. The current flow upon replacing the voltage source, E.
Figure 20. Current flow as charge accumulates (and voltage builds =
with a straight wire at time t 0 seconds. Initially the current flows at
up) on the capacitor immediately after applying the 9 volts shown in - 9 rnA since the current flows in an opposite direction from the pos
the circuit of Figure 19.With no charge on the capacitor initially, the itive current flow when the capacitor was charging up to equal the 9V
greatest voltage difference is seen across RI of Figure 19 and the great voltage source. As current flows. less charges are on the capacitor
est current flow occurs. As the voltage increases across the capacitor, plates and the capacitor voltage falls resulting in less current through
less voltage is present across the resistor, R I • and less current flows. the resistor, eventually approaching zero current flow as the capacitor
eventually approaching zero current flow. discharges.
106 - PART 1 FUNDAMENTAL PRINCIPLES
+lV_JJ_IJ
E ~l-~-.::J--O--C-· C Ec
Ec =_-__ L1---L_~·5V
V---V---- -O.5V
Figure 23. The smoothing of the leading edges of a square wave
input to a resistor/capacitor circuit as seen across the capacitor.
ALTERNATING CURRENT t
Most bioelectric phenomena of interest vary with time and
their electric potentials are not static as with a battery. Examples Water Momentum and Inductance
include action potentials of nerves or muscles. Even in most
power circuits, such as electric or florescent lights, voltages Figure 25. Analogy of a water fountain to an inductor. The momen
vary with time (in the United States at 60 Hz and in Europe at tum of the water in motion will allow it to continue to rise and then
50 Hz). When signals vary with time they can do so slowly, in fall back to the ground even if the push or pump is suddenly turned
which case they are said to have low frequency content. An ex off.An inductor will Similarly cause electrical current to continue to
ample is the surface recording of the compound muscle action flow momentarily even when the voltage originally causing the flow is
potential, with typical rise times of 5 ms and 15-20 ms dura turned off. The water's flow continues using up its kinetic energy.
tion. This means frequencies (the inverse of cycle time) are in whereas the electrical current flow uses up its magnetic energy to mo
the 50-200 Hz range, e.g., (l/5 ms) (lOOOms/lsecond) = mentarily continue its flow. Inductance is the property of how much
200/second 200Hz. Signals that change rapidly have higher magnetic energy is stored for a given current flow. This is similar to
frequency content. An example is the 250 microsecond rise time how powerful is the pump creating the fountain's ejection velocity. A
required in a single-fiber electromyographic study, indicating faster pump generates more kinetic energy for the same amount of
frequencies of 4 kHz or more, e.g., (11250 J.1S) (1()6lls/1 sec) = water and a larger inductor results in more magnetiC energy for the
4,OOO/sec =4 kHz. same amount of current flow.
Bioelectric signals usually have many different frequencies
that join to make up the complex waveforms seen.l The pres
ence of capacitance in a circuit such as the body can lead to dis itself can slow the rise time (especially attenuating the high fre
tortion of the actual signal due to its variable impedance at quencies) of single-fiber action potentials as observed when
different frequencies, thereby acting as a variable voltage di recording at a distance from the actual fiber. Muscle tissue
vider, altering the relative magnitudes of the frequencies ob offers various paths for current flow. The bilipid membranes of
served from the biologic signal of interest. Tissue capacitance the many adjacent muscle fibers can act as capacitors, each ac
cepting a certain amount of current flow before local voltage
changes in response to that current flow due to charge accumu
lation on these capacitors. This differs from the extracellular
pathways that are essentially resistive. Along these pathways
voltage varies directly and instantaneously with current flow in
Capacitor
=
accord with Ohm's law (E IR). The electrical model, or equiv
Impedance
alently acting electrical circuit, for a needle electrode five fibers
(Zd from a single-muscle-fiber action potential being recorded
looks like Figure 26. The crisp rapid rise of a single-fiber action
potential at the input of Figure 26 results in a slower rise at point
A. The current flow must accumulate on capacitor A before
voltage of point A changes. The voltage at point A then causes
f = frequency current to flow through resistor B, but the voltage at point B will
not rise as fast since current must accumulate on capacitor B
Figure 24. Variable capacitor impedance to current flow at differing before the voltage at point B changes. Each additional fiber
frequencies. The capacitor has infinite resistance at zero hertz (no (equivalent R-C circuit) results in further slowing of the rise
direct current, DC, can flow across the capacitors insulating dielec time. This delay or slowing of the rise time is one effect of
tric).At infinite frequency there is no time for charge movement to tissue capacitance that increases with distance between the bio
occur, so no voltage changes can occur. With no voltage change re logic signal source and measuring electrode in muscle tissue.
gardless of current magnitude, zero resistance is implied for the capac Each resistor and capacitor represents the extracellular pathway
itor at infinite frequency. past the fiber and the capacitance of that fiber's local membrane,
Appendix BASIC ELECTRICITY PRIMER - 107
A B C 0 E
+ +
Ein Eout
I I I I I
Figure 26. Electrical model of the behavior expected for five muscle fibers from the recorded active fiber. Each fiber's bilipid membrane serves
as a capacitor which can shunt current away from the recording electrode at Eo"!:' The extracellular fluid has a discrete resistance for the path
past each fiber. This results in a series of resistor/capacitor Circuits, one for each fiber.
respectively. Each resistor and capacitor couple is simply a du will not allow instantaneous current change without an infinite
plication of the simplest form of a low-pass filter arrangement. voltage being applied. An example is unplugging a home
Having several low-pass filters in a row causes the higher fre vacuum cleaner while it is running. One is attempting to instan
quencies to be progressively attenuated. Through this model one taneously change the current flow to zero in a device that due to
can better appreciate why muscle tissue acts as a low-pass filter, its motor has high inductance. The result is that vacuum cleaner
especially with increasing distances, and why slower rise times inductor's magnetic field energy creates a high voltage to resist
result. 3 the instantaneous decrease in current, resulting in a spark to the
wall socket (i.e., resulting in a slower decrement than instanta
neous). A similar principle is used with an automobile engine's
INDUCTORS coil to cause a spark across the spark plugs.
In biologic tissue, three-dimensional current flow occurs. In a
Just as objects with mass tend to remain in motion (Newton's metallic wire current is very concentrated and relatively large
first law), electrical current flow tends to resist change. A water magnetic fields circle it that decline rapidly with distance (Fig.
pump creating a fountain cannot instantaneously stop the flow of 27). The current flow in a volume conductor such as biologic
current (the water already in motion will continue to rise and then tissue can be considered a collection of many single lines of
fall over several seconds after the pump has been turned off) (Fig. current flow. Any two adjacent lines of current flow have mag
25). Similarly, the flow of electrical current resists instantaneous netic fields that cancel each other and add together outside of
change. This resistance to current change is called inductance both lines. With many adjacent lines of current in a three-di
and is usually such a small effect in biologic systems that it is mensional volume conductor the cancellation becomes defuse
negligible. Inductances are, however, important for understanding so that a significant magnetic field exists only outside of all the
the principles of isolated preamplifiers and transformers. lines of current. This places the magnetic field very far from the
Electrical inductance provides a voltage kick analogous to the center of all of these contributing lines of current, which due to
kick of a fireman's hose with an on/off nozzle attached. When distance makes the resulting magnetic field very small. The
the nozzle is opened it kicks back as the water current resist its magnetic field strength is also small because current flow in bi
initial flow. Rapidly closing the nozzle results in a kick in the ologic tissues is very small (microamperes as opposed to tens of
opposite direction. The resistance to water current flow changes amperes in the engine coil). These factors make the inductance
is due to the momentum of the water. The kinetic energy stored effects of normal biologic substrates at electrophysiologic fre
in its flow provides the kick to the nozzle. In electrical circuits, quencies negligible. At high frequencies such as used in mag
current flow builds up energy in a magnetic field that surrounds netically coupled short wave or microwave diathermy, the
the path of the current flow (Fig. 27).2 body's inductance effect does become significant.
With a coil, greater magnetic field amplitudes can be Since inductors resist changes in current per change in time,
achieved with the same amount of current flow due to summa inductance (L) is inversely proportional to AIlAt. Large induc
tion of the magnetic fields from each turn of the current path. tors allow less AliAt per voltage applied than small inductors.
This results in larger resistance to current change as energy Applying more voltage allows a more rapid current change, or
from the magnetic field must be built up or dissipated over time AllAt is proportional to E. Thus, AllAt =ElL.
before the current change can occur. Similar to a capacitor not At high frequencies of applied voltage across an inductance
allowing instantaneous changes in voltage across it, an inductor there is little time for the current to change and thus the alternating
tions in the space between them and thus cancellation of the mag \
netic field intensity in this region. The magnetic fields do align in /!(}
direction over a larger circle (thus weaker field due to distance) ~ = MagnetiC field
around both current lines. C.A coil allows multiple turns of a current
path to summate the magnetic fields down the central axis of the
coli. This allows buildup of a larger magnetic field per amount of cur
tI = Current flow
rent flow (i.e., more energy stored). Since this buildup is what is re
(r-----'""
Varying Magnet
Voltage Inductor. L } El Coil -'""'7~
Source
Magnet
Figure 28. A simple resistor/inductor circuit.
Voltage generated
as long as coil
current magnitude remains small. At infinite frequencies, the rotates
impedance of an inductor approaches infinity. The body's small
inductance becomes significant at the high frequencies of short Figure 30. The dynamo, or generator, is shown. By forcing the coil
wave diathermy, but not at the lower frequencies analyzed in to rotate in a constant magnetic field, the amount of magnetic field
electrodiagnostic evaluations. Applying 0 Hz voltage, no through the center of the coils will continually change. This induces a
change in current is being attempted after the constant DC cur sinusoidal current that increases and decreases in an attempt to
rents begin and thus the inductor's impedance is zero at 0 Hz. negate the flux changes through the coil. This is similar to Newton's
Thus, inductor impedance varies directly with frequency. second law. The attempt to place a magnetic energy field through the
Recognizing capacitor and inductor responses at zero and infi coil is resisted by the build up of sufficient current to create an equal
nite frequency helps one more easily understand their effects in and opposite magnetic field resulting in no net magnetic field build up
any particular circuit. in the coil. This requires energy that is provided by the force applied to
An inductor/resistor series circuit also acts as a variable volt spin the coil. (From Bergveld P: Electromedical Instrumentation: A
age divider over frequency due to the inductor's variable imped Guide for Medical Personnel. New York, Cambridge University Press,
ance over frequency, similar to the variable voltage dividers 1980, with permission.)
over frequency one can produce with resistor/capacitor circuits
(Figs. 23 and 28). also serve to amplify or attenuate original signal according to
Since change in the stored magnetic field energy is what is the ratio of turns. This is how neighborhood transformers
resisted, one circuit can be connected to another by coupling reduce (or transform) high-voltage power lines of 10,000 volts
only this magnetic field. Figure 29 shows such a coupler, called to 120 volts AC for in home use.
a transformer. I ,2 Isolation transformers allow one circuit to Electric generators, or dynamos, create current flow by me
follow changes in another without being directly wired together. chanically forcing a coil past a stationary magnet (Fig. 30). As
This helps to reduce some sources of electrical noise. the magnetic field is encountered, the generator's coil has cur
In Figure 29, the current 12 is greater than I) proportionally to rents induced that try to oppose the changing magnetic field
the number of turns since two full turns of 12 magnetic field strength. The current will flow in one direction as the magnetic
must cancel three full turns of I] magnetic field to maintain no field increase is being resisted, and then as the magnetic field
magnetic field change. The current required is 3/2 times larger, declines with movement of the coil's center away from the
i.e., 12 = 1.5 I). Thus transformers can both allow indirect or magnet, a current will be induced in the other direction trying to
electrically isolated interconnections between circuits, and can maintain the magnetic field. This is why spinning circular gen
erators (Fig. 30) intrinsically result in alternating current (AC)
as their primary output. I
FIL"rERS
Filters are often used to restrict the frequency content of the
signals evaluated. The desire is not to eliminate the biologic
signal's frequency, since this would distort the true potential's
waveform, but instead to minimize the effect of noise that may
t
Coil 1 Iron core
t
Coil 2
distort the true biologic potential's waveform. Noise is any po
tential measured that does not represent the actual biologic
event of interest. Unfortunately, noise is universally present but
Figure 29. Coupling circuits through an inductor's magnetic fields, can be attenuated by proper use of filtering without distorting
the transformer, is shown. The iron core concentrates the magnetic the potential of interest.
field so that almost all of the magnetic field generated by the coil la All resistances generate a certain amount of noise due to the
beled II tries to penetrate the central axis of coil L2. This results in thermal agitation of their atoms and electron clouds. This
current building up in coil L2 that tries to resist the magnetic field noise power is distributed uniformly over all frequencies and
being generated by current II flowing through coil LI.The resulting is proportional to the absolute temperature of the resistor. The
current 12 is said to be induced and is proportional to II by the ratio of voltage amplitude of this noise (EN) is defined by the equa
the number of turns of the second coil to the first (since the magnetic tion: EN 2 = 8KTBR, where K is Boltzmann's constant (1.38 x
fields of each try to be equal and are proportional to the the current IQ-23joulesfDKelvin), T is the absolute temperature in OK, B is
flowing and number of turns). the recording bandwidth, and R is the resistance of the biologic
Appendix BASIC ELECTRICITY PRIMER - 109
0
Frequency. Hz 1 1
F ---or--
L 21tRC 21tRL
+
R Eoul EoutiEin
0
Frequency, Hz 1
FH - -
21tRC or 21tRL
A B C
Figure 32. High-pass (allow high frequencies through unattenuated) and low-pass (allow low frequencies through unattenuated) filters. A.
Resistor/capacitor filter circuits. a,lnductor/resistor filter circuits. C, Frequency response of these equivalent circuits. Note the opposite locations
for capacitor and inductors relative to the resistor for each type. This is due to their opposite high- versus low-frequency impedance characteris
tics. FL and FH define the lowest and highest frequencies that pass relatively unattenuated in the high-pass and low-pass filters. respectively.
110 - PART 1 FUNDAMENTAL PRINCIPLES
The concepts of the capacitor and inductor allow us to see DIGITAL FILTERING
how filters can be made. Since capacitors and inductors have
variable impedance over frequencies, they can be used with a The majority of electrophysiologic instruments now use digi
resistor to make either high-pass or low-pass filters depending tal processing, including sampling the real-time (or analog)
on the circuit arrangement (Fig. 32).' signal at set intervals (which are points in time that occur at the
For the high-pass filter (which blocks the lower frequencies inverse of the sampling rate, I.e., 10 kHz sampling rates m~ans
from being transferred through the circuit), the capacitor pro values are taken each 0.1 ms) and digital, i.e., computerized
vides near-infinite impedance at the low frequencies, resulting mathematical filtering. The analog, or continuous real-time fil
in a very attenuated output. However, at high frequencies, ters described above suffer from phase distortion effects so that
almost no impedance is seen across the capacitor and negligible the frequencies near the cut-off settings of FL or FH are both at
attenuation occurs. The impedance of the capacitor equals the tenuated (typically to 0.707 of their value without the filter) and
impedance of the resistor at F L - An attenuation of 0.5 would phase-delayed or phase-advanced, which results in distortion of
therefore be expected, since half the voltage drop would occur these signals near the limits of our cut-offs. If the biologic
over the resistor and half across the capacitor. Due to phase ef signal of interest has frequencies near these cut-offs, the filter
fects (the voltage across the resistor varies directly and instanta will distort the resulting signal transferred from Yin to Vout'
neously with current, whereas the voltage across the capacitor is Digital filtering takes advantage of a digital processor's ability
delayed relative to current flow since charge must accumulate to store data, which can mean that prediction about future
on the capacitor before its voltage changes), the attenuation at values can be made (since time zero can be set arbitrarily at any
frequency FL is actually 0.707 _Considerations of capacitor and stored data value). A more perfect decreased phase distortion
inductor impedances near zero and near infinite frequencies filter with sharper roll-off can be constructed using powerful
help one to deduce the resulting attenuation expected over fre mathematical digital processing with the advantages of such
quency (called the transfer function or frequency response of predictive properties.
VoulVnJ·' One major pitfall to digital filtering is that only frequencies
below 112 the sampling rate, which is called the Nyqvist fre
quency, can be theoretically reconstructed. Any frequency con
BANDPASS FILTERS tent above 112 the sampling rate gets processed as though it
occurs at a frequency equal to the difference between true fre
The filter with the response comparable to that displayed quency coming into the device and some multiple of the sam
Figure 33 is called a band-pass filter. It is constructed by seri pling frequency, always resulting in an interpreted frequency
ally connecting a low-pass filter with its highest-frequency cut between zero and the Nyqvist frequency. This is similar to the
off, FH, to a high-pass filter with lowest cut off frequency, FL ; strobe effect where an accelerating rotating wheel appears to
where FH is greater than FL and the range from FL to FH is the speed up correctly, but then falsely appears to slow down and
band pass or frequency range allowed to pass through (Fig. 33). then reverse directions as the rotating frequency approaches and
Most electrophysiologic studies are performed with band-pass exceeds 112 the strobe light's (sampling) frequency. As the
filters in which both FL and FH are selectable. speed exceeds the strobe's sampling rate, it again appears to
speed up. but again slows and reverses as the speed exceeds one
and one half the strobe rate. This process repeats with increas
1.0 ing rotational speed or cycles per second. Thus one can only in
.707
terpret the true speed for zero to 112 sampling rate range of
HPF frequencies. Since low frequencies are of interest in electro
EoutJEIn physiologic studies, only the range from zero to the Nyqvist fre
quency (112 the sampling rate) is resolvable and higher
OL-____~------------____~__ frequencies must be first analog filtered out before the digital
Fl Frequency, Hz
filtering computer processing occurs. The processing error that
occurs for frequencies presented above the Nyqvist frequency is
1.01-----------.......
called aliasing and is a problem inherent to sampling. For
.707 - - - - - . - - - -..----.~.---.--..,-. tunately, modern digital equipment allows very fast sampling so
LPF e...;e,.. the range of biologic frequencies of interest is usually much
below the Nyquist frequency for most devices. However, analog
OL-_ _ _ _ _ _ _ _ _~~~~~ low-pass prefiltering with cut-off below the Nyqvist frequency
FH Frequency. Hz to eliminate all frequency content at or above 112 the sampling
rate before sampling occurs is still necessary. If this limitation is
not observed, severe distortion of the actual signal can occur as
1.0 higher frequencies become interpreted as lower-frequency con
Band .707 tent of the signal.6
Pass e...;e,.. Another limitation to digital filtering has to do with the fre
FiHer quency domain mathematics inherent to the process.s To com
pletely transform the incoming real-time analog signal into the
O~___~-------~--- full frequency domain it must be observed for all time, past and
FH Frequency. Hz
future. Since we do not have that much time or knowledge, we
Figure 33. Band-pass fllters.A low-pass filter (LPF) in series with a compromise by using a segment of time called a window. which
high-pass filter (HPF) result in the band-pass filter (if FL < FH ; other is the time required for one trace to sweep across the electrodi
wise all frequencies would be attenuated). agnostic instrument's video screen. It is then assumed that this
Appendix BASIC ELECTRICITY PRIMER - III
trace repeats and has repeated forever. This means the most fun ORIGINAl RECONSTRUCTED
SQU_RE WAVE SQUARE WNIE
damental frequency within this analog signal segment is lIT,
y
where T is the time duration, or time window, we have chosen. Y
I I
The resulting analysis and computations result in creating r--~I~-....,}"'I'" of A
values only at frequencies that are multiples of this fundamental I
I
frequency. This limits how accurately we can reproduce the I
analog signal after applying the desired digital filtering. I
Additionally, due to discontinuities at the edges (where the be .
I
msec. 5 41 5 45
1.0
I
Figure 35. The diode (0). or rectifier is dia
grammed. This unique device has essentially no resis
r. Diode. D
Ein
-1.0
0+--\--+---1t-.----#
Time
Signal to Noise =
DIFFERENTIAL AMPLIFIERS
SIN = Vex100 I VNC x100 = 1mVl1mV = 1.0
---tI> Sample ---tI> Sample & Hold --to> Digitize to --to> DIA, Digital to --to> Low Pass
Binary Code Analog Conversion Filter Smoothing
of Output
1st digit
0:: positive
1:: negative
nme Amplitude
0.0 10000
Vas 0.1 10010
0.2 10010
0.3 10000
0.4 00011
0.5 00001
0.6 00011
0.7 10001
0.8 10101
0.9 11010
1.0 11100
1.1 11001'
1.2 10011
1.3 10001
1.4 10000
1.5 10000
Figure 38. Digital processing of a real-time (analog) signal is shown. The signal is sampled and held until the computers' cycle time allows the dis
crete value for that particular time to be recorded. It is then encoded into binary numbers that digital processors can manipulate. If sampled fast
enough, the real-time signal can be reproduced by DIA conversion and smoothing with low-pass filtering, although time-delayed. Since this delay
can be arbitrarily long. digital processors make excellent delay lines for trigger and delay operations or data storage.
114 - PART 1 FUNDAMENTAL PRINCiPlES
only certain discreet values for amplitudes, usually over a 2 8 predict the electrical behavior of biologic tissues. Electro
(256) to 2 16 (64,000) range of values. This is due to the neces physiologic studies inherently require appreciation of the electri
sary binary encoding. The process of turning a continuous real cal events under study. Analyzing such events in terms of simple
time signal into a series of binary numbers that a computer can circuit elements can help solidify one's understanding of the
analyze requires an analog-to-digital converter, or AID (pro meaning of the recorded bioelectrical potentials and possible
nounced "A to D"). This device samples the real-time signal at electrophysiologic pitfalls involved in interpreting such signals.
discrete intervals and rounds its magnitude off to the nearest
digital value (Fig. 38). An inverse device, the D/A (pronounced
"D to A") or digital-to-analog converter, creates analog stair REFERENCES
step values that change at each sample interval. This stair-step
output can be smoothed by analog filters, usually low-pass fil L Bergveld P: Electromedical Instrumentation: A Guide for Medical Personnel. New
York, Cambridge Uuiversity Press, 1980.
ters, to look very similar to the original input if no other pro 2. Cromwell L, Arditti M, Weibell PI, et a1: Medical Instrumentation For Health
cessing was performed on the signal digitally (Fig. 38).6 Care. Englewood Cliffs. NJ, Prentice-Hall, 1976.
3. de Weerd JPC: Volume conduction and electromyography. In Notermans SLH:
Current Practice of Clinical Electromyography. New York, Elsevier. 1984, pp
9-28,
CONCLUSION 4. Geddes LA, Baker LE: Principles of Applied Biomedical Instrumentation, 3rd ed.
New York, John Wiley & Sons. 1989.
Basic conceptualizations of electricity and the electrical cir 5. Maccabee PJ, Hassan NF: AAEM Minimonograph #39: Digital Filtering: Basic
Concepts and Application to Evoked Potentials. Muscle Nerve 1992;15:865-875.
cuit elements like resistors, capacitors, inductors, rectifiers, am 6. Nunez PL: Electric Fields oflhe Brain. New York, Oxford University Press, 1981,
plifiers, and switches can be powerful tools to understand and p80.
Chapter 4
Neural insult can be conceptualized as occurring over local of injury, the axon itself is damaged, and the entire nerve (axon
ized individual nerve segments (focal process), or affecting ex plus myelin sheath) undergoes disintegration distal to the injury
tensive portions of the peripheral nervous system (generalized and must be completely regenerated prior to the return of func
process). Localized neural insults can produce three broad cate tion. A more generalized neural injury can produce either of the
gories of nerve injury (Table 4-1). latter two types of nerve damage but may be more prone to pro
1. Minimal neural insnlt: rapidly reversible conduction ducing severe axonal loss or generalized demyelination as op
block with focal action potential propagation failure secondary posed to a focal loss of conduction because of its generalized
to short periods of ischemia. There is the possibility of nerve nature.
conduction slowing if incomplete neural blockade is present Although there are a multitude of specific entities that can
with sparing of the relatively slower conducting fibers, Le., pref affect the anatomic and physiologic status of peripheral nerves,
erential blockade of the fastest-conducting fibers. the nerves' response to an insult is limited (Table 4-1). For ex
2. Intermediate neural injury: failure or slowing of action ample, a traumatic injury may disrupt the structural integrity of
potential propagation secondary to focal demyelination without an entire peripheral nerve whereby the axon and surrounding
axonal damage producing a prolonged conduction block and re myelin demonstrate predictable changes (see below). On the
duced nerve conduction velocity (NCV). other hand, a toxic substance may preferentially affect just the
3. Severe neural insnlt: action potential propagation failure axon with resulting denervation of the muscle fibers and the
with axonal damage, i.e., Wallerian degeneration. supplied sensory end organs. A few hereditary and acquired
In the first two designations of action potential propagation disorders specifically affect the myelin enveloping the periph
failure, there is a temporary loss of neural conduction across a eral nerves resulting in slowing of neural conduction. Other
focal lesion while the axon's structural integrity is preserved. In hereditary neuropathies and most acquired neuropathies are as
this situation, it is possible for the enveloping myelin sheath to sociated with a primary axonopathy. Finally, there are meta
be spared or disrupted, but with restoration of blood flow or bolic diseases that can disrupt both the axon and myelin,
myelin recovery, nerve conduction is restored. In the third type producing a combined demyelinating and axonal injury.
115
116 - PART I FUNDAMENTAL PRINCIPLES
Table 4-1. PERIPHERAL NERVOUS SYSTEM RESPONSE Table 4-2. Pathological Basis of Altered Action Potential
TO INSULT Propagation
neural regions affected. 22,26,65,74 The majority of work investigat distally.47 As time progresses within the first several days, the
ing the various aspects of Wallerian degeneration has been per myelin continues to retract producing further node of Ranvier
formed in animals and not in humans. Despite this limitation, widening, and there is an accompanying increase in the
the majority of animal findings are believed to be directly ap Schmidt-Lantermann incisures.312 It appears that the larger
plicable to humans. nerve fibers demonstrate this myelin alteration prior to it being
observed in the comparatively smaller nerves. During this time,
Sequential Changes the Schwann cell's nucleus enlarges and there is an increased
Axonal Component. A nerve fiber consists of a single axon amount of visible chromatin. Of note,· the endoneurial fibrob
with its investing myelin sheath. A peripheral nerve trunk is lasts begin to proliferate (Fig. 4-1). If there has been sufficient
comprised of multiple nerve fibers, both myelinated and un trauma to surrounding tissues, the vascular structures demon
myelinated, If the nerve trunk is compressed to the extent that strate endothelial swelling and multiplication of adventitial
the supporting connective tissue structures are not disrupted, but cells. 32 By 72 hours, the myelin sheath formerly comprising the
the axon is injured, then axonal degeneration ensues. This type internode region now forms segmented ovoids engulfing the
of injury can be reproduced experimentally by crushing the previously noted axonal segments (Fig. 4_1).243 These myelin
nerve with a hemostat. At the site of crush, endoneurial edema ovoids containing fragments of axon are noted to be present
can be observed within 1-2 hours as well as a surrounding zone within 72 hours in all transected nerves. There are also noted to
of hyperemia. 204,225 The endoneurial edema occurs because of be myelin ovoids without axonal fragments. Also, multiple and
the capillaries' increased permeability secondary to the induced distinct nucleoli are observed in the Schwann cell nuclei.
trauma. 133 .227 By several hours, the axon within and surrounding Beginning approximately 4 days after insult, the Schwann cell
the crushed region is beginning to break apart. At about 72 nuclei start mitotic activity and produce an increase in the
hours following the crush, Schwann cells are in the process of amount of cytoplasm. 2M ! The Schwann cells then continue to
digesting myelin and axonal SUbcomponents, and preparing the undergo significant mitosis and proliferate. This is particularly
endoneurial sheath for the regeneration of axonal sprouts from noticeable at the severed nerve ends where these cells are at
above the lesion site. 46•132 tempting to bridge any gap that may be present if the nerve is
Immediately following transection, as opposed to the less severed.1,192 At about 10 days, the entire axon length distal to the
severe crush injury, a small amount of intra-axonal fluid leaks lesion has been converted into a series of myelin ovoids. The
from both the proximal and distal severed ends of the nerve segments of the axon contained within the myelin ovoids even
(Fig. 4_1).195.328 The severed nerve ends retract secondary to the tually disappear, prompting some investigators to refer to the
elastic properties of the endoneurium.242.281 The inciting trauma ovoids as "digestive chambers."243 The Schwann cells contain
also disrupts capillaries, which results in a localized hemor ing the remnants of axon and myelin are referred to as
rhage and increased permeability of the surrounding vascula "myelophages" and the peak of myelin chemical breakdown
ture. Macrophages and mast cells then invade the injury site. occurs about 14 days after the inciting incident.
Within a few hours of injury, the portion of nerve no longer in The inciting traumatic event has caused mast cells to enter
contact with the cell body begins to demonstrate a diffuse the tissue and release histamine and serotonin, thus generating
swelling. Approximately 7-10 hours after the insult, an eleva further edema, capillary seepage, and the entrance of macro
tion in the amount of intra-axonal osmophilic particles and vac phages into the traumatized region. 8•226 Mast cell numbers con
uoles are noted. It is believed that this accumulation of particles tinue to increase after the insult and maximize by day 4, and
represents endoplasmic reticulum dilatation and mitochondrial maintain this level until approximately day 15 with a continued
swelling and has been definitively observed by 19 hours.114.189 reduction thereafter, reaching normal numbers by about 4
There is also noted to be an aggregation of the neurofilamentous weeks. 282 The above-described processes occur within the
material. At this point, there are no gross light microscopic nerve's endoneurial tube. During this degeneration process, the
structural abnormalities beyond the region of damage. By 48 Schwann cells and invading macrophages from the site of ac
hours, however, a number of additional changes are noted. companying vascular injury ingest the myelin and disintegrat
Specifically, the axon appears rather pale and somewhat more ing axonal fragments. 21.102,134.i84,327 These fragments have usually
swollen and is more difficult to stain with routine tech been completely removed by 35 days. After about 4-5 days, the
niques.20.194 Within the nodal and paranodal regions mitochondr endoneurial tube contains a mass of proliferating Schwann cells
ial aggregations appear. The neurofibrils begin to disintegrate ingesting axonal components and myelin, macrophages, myelin
and decompose into their subcomponents. At about 48-72 ellipsoids, and lipid droplets. At 2-4 weeks this mass of
hours, the axons begin to fragment and form spiral or hook-like Schwann cells and minor amounts of cellular debris forms the
segments (Fig. 4-1). Axonal discontinuities originate initially at so-called bands of BOOgner (Fig. 4-1 ).41 It has been estimated
the nodes of Ranvier and later further subdivide the axonal seg that the number of nuclei approximately 25 days after injury is
ments by forming breaks at the internodal regions. Within 96 8 times greater than is normally present within the endoneurial
hours, the entire axon is completely disintegrated and confined tube. The proliferation of nuclei persists at 225 days but is re
to small myelin ovoid fragments. At 7 days, there is noted to be duced to approximately 5 times normal. The number of en
a complete absence of axon organelles.!88 Although there is con doneurial tube nuclei is directly dependent upon the amount of
siderable overlap, the breakdown of the axon may precede that debris required to be ingested. As the axonal material and
of the myelin by a short period. myelin are reduced, there is a concomitant reduction in the cel
Myelin Component. Within the first 24-36 hours, and re lular mitotic activity.123 The endoneurial tube shrinks to a diam
ported to have begun by 6-16 hours of neural insult, the myelin eter of about 10 11m and can remain in this condition and size
begins to retract from the axons at the nodes of Ranvier.46.243 for many months. awaiting the return of an axon from p"roximal
One group of investigators has observed myelin degeneration to the site of injury. After about a year, however, the endoneurial
within 2 minutes following a crush injury.322.323 This myelin re tube is encompassed by surrounding connective tissue and
traction is initiated at the site of the lesion and then progresses begins to be further reduced to approximately half its original
118 - PART I FUNDAMENTAL PRINCIPLES
B
>,c:::.
'),
...
,'t $Ii
>1'
.,...
S;
~ :::s::
Figure 4-,. Wallerian degeneration following neural section. A,
Region of nerve under consideration including that portion of nerve tran
sected and viewed in more detail below (region between horizontal lines).
B, Magnified portion of nerve between horizontal lines to be included in the
injury zone. C.Appearance of nerve within first day following injury. Leakage
of axoplasm from proximal stump and separation of proximal and distal as
peets of nerve. D. On day 2 follOWing trauma, the neurofibrils in the distal
axon and for a small distance proximally have disappeared. There is also
some shrinkage of the axon that appears rather irregular. Myelin is also be
ginning to retract from the nodes of Ranvier. E, By day 3, there is fragmenta
tion of the axon and myelin. Schwann cells undergo mitosis and proliferation
and begin to digest the previous myelin components. F. On about day 8 the
axon fragments have been digested and Schwann cells are attempting to
bridge the gap between the 2 neural portions. Regeneration of proximal
axon portion is noted with several neurites branching and evincing distally
along the outer margins of the myelin ellipsoids. G.At approximately day 12
there is a lessening of the gap separating the two nerve portions and there
is continued advancement of the growth cone. H, In this particular instance
the gap separating the two neural aspects is dosed by the proliferation of
Schwann cells and fibroblasts, which occurs roughly by day 20. The mass of
Schwann cells (and in neural section fibroblasts) forms the band of Bungner
into which the growing axon penetrates. In this particular diagram a neurite
is seen to not only enter the band of Bungner but also form an aberrant
G
route external to the nerve proper. I, On day 100 the neural continuity is
established and all debris has been removed. Neural diameter remains less
than the original size and myelination is not yet present. J, Certainly by day
200 the myelin is established but at a significantly reduced thickness when
H compared to preinjury values.There is also noted to be a decrease in the in
ternodal distance, Le., an increase in the internodes over the same length of
nerve. Modified from Bots G Th: Pathology of nerves. In Vinken PJ, Bruyn
GW (eds): Handbook of Clinical Neurology,Vol. 7, Diseases of Nerves (Part
1).Amsterdam, North-Holland Pub. Co., 1970. pp 197-243.
cross-sectional area.2.149.279 With respect to the axonal fragmen portions of the nerve is examined to gain a better appreciation
tation, it is believed that this process occurs simultaneously over of the histologic basis for clinical and electrophysiologic find
the entire length of the distal aspect of the nerve. The myelin ings noted in peripheral nerve injuries.
changes, however, may proceed in a more proximal to distal se Nerve Fiber Degeneration. In addition to the neural
quence somewhat lagging behind the axonal segmentation changes occurring distal to the injury site, there are degenera
process,I21·257 or occurring concomitantly with axonal disrup tive alterations of the nerve also transpiring for a variable dis
tion.2O.243 The actual sequence remains debatable. tance proximal to the injury site. Depending upon the degree of
damage inflicted on the nerve, there is a similar pattern of
Retrograde Neural Changes Wallerian degeneration progressing along the nerve proximally.
An insult to the peripheral nervous system typically results in Minor injuries that do not disrupt the endoneurium, such as a
a reaction to the inciting trauma not only distal to the injury but crush, lead to proximal Wallerian degenerative changes extend
proximal as welL This proximal reaction can be localized to ing for several millimeters. Lesion producing severe disruption
three regions: (1) peripherally; at and about the injury (within or transection of the entire nerve can generate retrograde degen
several centimeters) as well as major portions of the nerve prox erative changes extending for several centimeters.67.193.281
imal to the injury zone (nerve fiber degeneration), (2) cell body Proximal to the injury the axons become swollen, which may be
no longer connected to its axon (axonal reaction), and (3) neural a result of both edema formation and blocked axoplasmic flow
synapses (trans-synaptic neuronal reaction).281 Each of these (Fig. 4-1). The support for axonal transport disruption is based
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 119
but do demonstrate the other characteristics of the reaction to one axonal sprout present for any period of time. Within a short
nerve injury. time there is resorption of the multiple axonal sprouts and the
Chromosynthesis Phase. If a cell and its extensions are formation of one dominant axon. After 24 hours, the advancing
completely located within the central nervous system, degener terminal axons appear as small terminal buds with mUltiple
ation is the likely result of neural injury. The majority of cells smaller club-like terminal axonal branches extending into the
projecting peripheral nervous system axons, however, experi damaged area by 3-8 days (Fig, 4-1). The distal expansio~ of
ence a recovery phase. Complete recovery is dependent on the the axon tip or growth cone as directed by the cell body serves
axon proximal to the site of injury bridging the injured site and to increase the longitudinal extent of the axoplasm. 2s1 The
establishing physiologic continuity with its appropriate end growth cone extends several extensions referred to as filopodia
organ. The beginning of chromosynthesis is usually demarcated or neurites. Elongation of the regenerating axon is accom
by the earliest change noted in the neuron, which is a reforma plished by an ameboid type of motion of the filopodia. In minor
tion of the granular Nissl substance. Nissl substance formation traumatic injuries with no disruption of the endoneurial tube
is first observed at about 2-3 weeks following injury if there has structure, axon tips have been detected below the injury site
been little disruption of the endoneurial tube. Recovery then within 4-10 days subsequent to the incident,79.125,133.216.275 It is
proceeds and requires approximately 10 weeks for the cell to possible for the advancing axonal tip to arrive at the distal por
again appear as it did prior to the injury (Fig. 4-2). In severe tion of the endoneurial tube when the Schwann cells still con
nerve trauma with disruption of supporting connective tissue tain debris from the previous axon. In this case, there is little, if
structures, it may take more than 4 months before the neuron any, hindrance to axonal penetration offered by the partially di
demonstrates signs of recovery. An additional early sign of neu gested axonal fragments and myelin,60,281
ronal recovery is that the nucleus returns to the central portion If there has been sufficient trauma to the nerve resulting in
of the cell and the swelling resolves. 68 ,69,281 Also, neurofibrils are scar formation with a gap between the two nerve ends, success
reformed and the Golgi system, again, becomes perinuclear. ful regeneration depends upon the length of time since the injury,
The extent to which a cell experiences the axonal reaction de age of the subject, and content of the scar. Axonal sprouts may
pends upon the severity of injury,41 the subject's age,122 and the appear within 6 hours of injury.233 One axon can give rise to mul
distance between the cell body and level of injury.294 tiple collateral sprouts thus forming an intra-endoneurial tube
Degenerative Phase. Should the injury be severe enough plexus by 48 hours with only a few collaterals eventually pene
that continuity is not established peripherally, then the cell body trating the zone of injury to enter the distal band of BOngner. Up
is likely to proceed from the chromatolytic to the degenerative to 50 axonal sprouts have be observed to arise from 1 axon and
phase (Fig. 4-2), Degeneration is highly variable and may occur more than one of these sprouts may enter the same endoneurial
in weeks or require several months. 281 Experiments attempting tube. 62,314 It is then possible for up to four of these axonal sprouts
to define the extent of cell body loss have demonstrated a range to acquire a myelin sheath, but one eventually dominates, pre
of 6_50%.15,256 The extent of degeneration is dependent upon serving the ratio of one axon per endoneurial tube. Occasionally,
lesion severity. it may be possible for two or more axonal sprouts to remain
Trans-synaptic Neuronal Reaction. Perineuronal glial within one endoneurial tube and successfully reinnervate an end
cells demonstrate an increase in number and size within 24-48 organ (e.g" muscle). Although not proven, this may be the expla
hours of injury, 167.229 Both microgliacytes and astrocytes partici nation of the axon reflex. The terminal buds are then converted
pate in this reaction. In rather severe lesions, the microglial cells into terminal repeatedly branching forks by 30 hours, trying to
appear to cause a separation of the affected neuron's synaptic penetrate the wound region containing necrotic tissue by passing
connections with other cells. 199 This action may help in isolating directly through or around it in an attempt to re-enter the en
the reactive neuron from receiving input by way of neurotrans doneurial tube. Within the first 3 days, the wound region is filled
mitters, thus allowing it a quiescent period to primarily perform with exudate (blood and plasma) and a fibroblastic network,32If
the necessary repairs of its peripheral extension. The actual the axon sprout encounters a substance inhibitory to further
process and substances responsible for this reaction are not en progress (e.g., blood clot, fibrous tissue, fat. scar, etc.), it may bi
tirely known. Recovery results in a return of the preinjury state furcate, double back, go around the obstruction, or form a termi
with synaptic terminals being established requiring approxi nal bulb or spiral of Perroncito (Fig. 4-3). Following neural
mately 4 months after anatomic recovery,245 These same cells transection or neural repair, it has been estimated that about 116
may function in a phagocytic role should the neuron degenerate. to In of nerve fibers may eventually terminate in the desired end
organ. 243 By day 5, Schwann cells have penetrated the wound
NEURAL REGENERATION region and allowed axonal branch passage to be much easier. It
is unclear exactly what factor(s) guide the neurites across the in
The origin of neural regeneration is that portion of the axon jured site to reach the distal site of the axon. For narrow nerve
proximal to the lesion location contained within the undamaged gaps, fibroblastic tissue rapidly unites the two nerve ends and
endoneurial tube (Table 4-2). Within 6 hours following an injury neurites may follow the fibroblastic bridges. Rather wide gaps
severe enough to result in Wallerian degeneration, the terminal lead to neuroma formation and thus permit only a few axons to
portion of the intact proximal nerve stump becomes differenti bridge the gap. In optimal situations with only minimal gaps, it
ated from that portion of the nerve about to begin the previously may take up to 8-15 days for the growing axons to reach the en
described degeneration process. The distal portions of the sur doneurial tubes. The regenerating axons usually have a diameter
viving viable aXons begin to swell and each axon may give rise of roughly 0.5-3.0 JlIll and penetrate the scar region at 0.15-0.24
to two or more axon branches or sprouts, which have been re mmJday, but can reach speeds of 2.5-4.0 mmJday once in the
ferred to as neurofibrillar brushes.32,m In simple lesions with distal portions of the endoneurial tubes. 243 Individual human
little edema formation and preservation of the endoneurial tube, nerves have various growth rates: median (2.0-4.5 mmlday),
terminal portions of the regenerating axons penetrate the dam ulnar (1.5 mm/day) and radial (4.0-5.0 mmlday),17 The rate of
aged area and beyond by 24 hours, and there is rarely more than axonal growth is proportional to the distance of the growth cone
Chapter.. PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 121
from the cell body. The closer the injury to the cell body, the b
faster the rate of growth with a proportional slowing the further
the insult is from the cell body. Also, at any given distance from
the cell body, the rate of axonal growth is the same irrespective
of the original lesion site for a particular nerve. Therefore, for
proximal lesions, the rate of axonal growth is faster than for the
more distal locations, i.e., the growth rate slows as the growth
cone advances.181
When the axon tip finally reaches the distal aspect of the en
doneurial tube containing the Schwann cells, there is an align
ment of Schwann cells about the advancing axon. Once aligned,
the Schwann cell begins to rotate about the axon to form a mul
tilayered structure of the myelin sheath. The formation of the
myelin sheath about the axon is approximately 9-20 days
behind the advancing font of the axon. 139.240.264 Myelination,
therefore, follows the progression of the axon distally at a rate
of approximately 4 mmlday.239 The natural separation between
the Schwann cells forms the node of Ranvier, while the seg
ment of myelin containing the Schwann cell nucleus is called
the internode region. Unlike the internode segment prior and
proximal to the injury, there is a shorter distance from one node
of Ranvier to the next.144.157.293 In other words, there are more
nodes of Ranvier over the regenerated nerve compared to the
region prior to the injury (Fig. 4-1). It may take approximately
one year or more for the myelination to fully mature. 250
Within about 3 months following the injury, the denervated
endoneuria I tubes are 3 Ilm in diameter or smaller. 279 This repre
sents the maximum shrinkage of the endoneurial tubes and they
stabilize at this diameter. Upon neural re-entry into the en
doneurial tube, the bands of Biingner or Schwann cell mass
helps guide the returning axon. It is unlikely, however, for the
Figure 4-3. Endoneural tube disorganization. Following neural
endoneurial tube to ever regain its diameter prior to neural
transection there is often major disorganization of the endoneurial
injury.s If the endoneurial tubes are not reinnervated by approx
tubes as well as interposed connective tissue between the 2 ends of
imately 1-1.5 years after denervation, they are less susceptible
the severed nerve. The axon attempts to grow from the central por
to receiving an axon because of Schwann cell replacement by
connective tissue. 2s1 tion of the injured nerve (A) across the scar region (C) to reach the
In lesions primarily involving crush, cold, concussion, or distal aspect of the nerve (B). There is a significant amount of disorga
compression, the endoneurial tubes remain intact and there is nization with respect to the regrowth of the neurites. Some do indeed
cross the scar with some bifurcation prior to entering distal en
relatively little difficulty in the axon regrowing across the dam
aged section. Therefore, the nerve re-establishes contact with doneurial tubes (c) but multiple others are misdirected (a) or simply
proliferate in connective tissue forming the so-called spiral of
the original end organ to again reinnervate the intended struc
Perroncito (d). (From Bots G Th: Pathology of nerves. In Vinken PJ,
ture. When there is physical separation between the cell body
and end organ, reinnervation is less assured. There is a distinct Bruyn GW (eds): Handbook of Clinical Neurology,Vol 7. Diseases of
possibility for the newly formed neurites to enter inappropriate Nerves (Part I). Amsterdam. North-Holland Pub. Co.. 1970, pp
endoneurial tubes (Fig. 4-4). For example, sensory neurites may 197-243.)
enter an endoneurial tube destined to end in a muscle fiber
while a motor neurite can be directed to a sensory end organ. In If the axon eventually reaches the end organ, the process of
both cases, the regeneration is useless-or even counterproduc axonal maturation is capable of proceeding. The axon begins to
tive-because the inappropriate end organ is reached. The fac increase in diameter in a proximal-to-distal direction. 149 The
tors redirecting neurites toward appropriate endoneurial tubes is Schwann cells forming the bands of Biingner begin to increase
less than 100% effective and poorly understood. There is a com in size and become longitudinally oriented about the newly
petitive process in muscle tissue following a partial injury to a formed axon. There may be more than one neurite within a
motor nerve. While the axonal sprouts are regrowing down the single endoneurial tube. The eventual fate of these neurites may
endoneurial tube, collateral sprouting is also occurring within be that two individual myelinated nerves are formed or they
the muscle tissue. Intact nerves send out collateral sprouts to may combine into a single axon. As previously noted, the
reinnervate neighboring muscle fibers.82.147 In this case, it is en Schwann cells begin to rotate about the axon in the process of
tirely possible for there to be little muscle tissue left to reinner myelin formation. Schwann cell nuclei take on a more elon
vate by the original nerve as the process of collateral sprouting gated appearance in this alignment process. As myelination pro
has already accomplished the required reinnervation. It is also gresses, segmentation of the myelin begins with a single
possible for remaining sensory nerves to increase their area of Schwann cell comprising an internode region and nodes of
distribution somewhat to provide cutaneous sensibility to a pre Ranvier accounting for the production of the internodes. The
viously denervated region of skin prior to neural regrowth from process of myelination may begin as early as 3-4 weeks follow
the injured site.276.313 ing a transection starting proximally and progressing distally.2Q9
122 - PART I FUNDAMENTAL PRINCIPLES
figure 4-4. Nerve transection.There is sprouting of multiple neurites from a single axon (spr) surrounded by a common basallamina.At the
end of each sprout or neurite there is a growth cone (gc).The sprouts cross the injured zone associated with Schwann cells (Schw) attempting to
reach the distal nerve stump. Found within the injury zone are macrophages (m), fibroblasts (fb), mast cells (me), and blood elements. Upon reach
ing the distal nerve stump, the sprouts attach and enter the band of BUngner.lt is rather obvious how misdirection of axonal sprouts is a common
occurrence. (From Lundborg G: Nerve Injury and Repair. Edingurgh. Churchill Livingstone, 1988, with permission.)
If there has been enough neural trauma to result in a separa the nerve, which requires the Schwann cell to ingest and then
tion of the nerve, the chances of successful reinnervation are de resynthesize a new myelin layer. Usually, only one or a few in
creased. As time passes, there continues to be collagen ternodal segments are affected in segmental demyelination,
deposition within and about the endoneurial tube, resulting in a which is quite different from the degree of Schwann cell alter
progressive thickening of this structure.159.279 Should reinnerva ation noted in Wallerian degeneration. 235
tion occur within the first year, the final axonal diameter may be The process of segmental demyelination is typically re
reduced to 75% of the original diameter, but this does not stricted to a focal segment limited to several internodes of
appear to impede neurite penetration or the nerve's eventual nerve, although multiple proximal and distal foci can be pre
physiologic properties,75.279 The final result of regeneration is sent. The nerve's axon and myelin not immediately adjacent to
usually a nerve fiber that is smal1er in diameter, thinly myeli the damaged region are relatively unaffected. Through an un
nated, and associated with shorter internodes. known process, the majority of the above nerve diseases exert a
direct toxic effect on the Schwann cell itself or the myelin
SEGMENTAL DEMYELINATION sheath while sparing the axon. Of course, if the demyelinating
disease is particularly profound, it is possible for the axon to be
As noted above, if the axon is injured, one can anticipate the secondarily injured, resulting in Wallerian degeneration.
characteristic pattern of Wallerian degeneration to ensue. It is Unlike Wallerian degeneration, it is much more difficult to
rather common, however, for a nerve to be affected by a disease accurately document a characteristic pattern of changes with
process or other insult that does not damage the axon, but pref segmental demyelination because of the variable nature of the
erentially injures the nerve's myelin (Table 4-2). In this in types of diseases capable of generating this lesion. Initially, the
stance, the damaged myelin is removed and replaced in the myelin sheath begins to appear somewhat granular with moder
process known as segmental demyelinationlremyelination (Fig. ately sized vacuoles and lipid droplets compared to the rather
4-5). Throughout the demyelinationlremyelination process, the larger ovoids seen in Wallerian degeneration (Fig. 4_5).120 In ex
axon and surrounding endoneurial connective tissue remain perimental segmental demyelinating investigations (e.g., diph
undisturbed and intact. A few of the diseases known to produce theric polyneuropathy), 5-8 days following injection of a toxin,
varying degrees of demyelination are: Guillain-Barre syndrome, initial separation of the myelin lamellae were noted at the nodes
chronic inflammatory demyelinating polyradiculoneuropathy, of Ranvier and Schmidt-Lantermann incisures, and these
diabetes mellitus, leukodystrophies, and several forms of changes correlated with the subject's clinical symptoms. 309•316 In
Charcot-Marie-Tooth disease (Table 4_3).6Q·91.1 15.122.287.296.311.325 In experimental allergic neuritis, the first changes noted were sep
short, if a nerve experiences an insult that does not produce aration of the terminal myelin loops in the paranodal region. 14
Wallerian degeneration, chances are that at least segmental de Within 7 days of these observations, the myelin sheath began to
myelination may appear. This insult results in a malfunction of disintegrate. The Schwann cells increased in number beginning
the Schwann cell to either maintain or continue to produce for a about the nodes of Ranvier. By 8 days following the onset of
period of time, the protein and lipoprotein synthesis required to myelin breakdown, macrophages and Schwann cells began in
sustain a myelin sheath.49 It is also possible for compressive or gesting the myelin and other breakdown products. The axon and
ischemic episodes to structurally derange the myelin surrounding immediately surrounding myelin layer were essentially spared
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 123
III
IV
V
==========~~s:a 19 '*
Figure 4-5. Segmental demyelination. I, Overall view of the nerve prior to injury with the section contained within the box magnified in the
subsequent sections. II. Region of nerve (one internode) affected by a disease process resulting in myelin breakdown of this segment only. III. Myelin
is being digested and there is proliferation of Schwann cells. IV, The myelin has been completely removed. V. Remyelination is complete. Note that
over this segment previously containing one intemode. there are now three intemodes. (Modified from Bots G Th: Pathology of nerves. In Vinken PJ,
Bruyn GW (eds): Handbook of Clinical Neurology.Vol. 7, Diseases of Nerves (Part I). Amsterdam. North-Holland Pub. Co., 1970. pp 197-243.)
in most segmental demyelinating processes. The general ap neural insult. The degree to which a nerve is damaged has impli
pearance of the affected portion of nerve was that of a relatively cations with respect to its present function and potential for re
thinly myelinated nerve, often surrounded by Schwann cells and covery. There are two general classification systems (Table 4-4).
macrophages ingesting the affected myelin. Once the affected One is that of Seddon, which considers neural injury from the
myelin was significantly removed. Schwann cells proliferated perspective of a combination of functional status and histologic
and began to remyelinate the affected segment of nerve, usually appearance. Although there are a number of factors that may
by 14 days. Just as in Wallerian degeneration, there were signif affect the nerve, the devised terminology primarily, though not
icantly more internodes and accompanying nodes of Ranvier exclusively, considers mechanical trauma (compression, stretch,
than prior to the injury (Fig. 4-5). crush, concussion, or various degrees of transection) to be the
inciting incident. In Seddon's scheme, there are three degrees or
NERVE INJURY CLASSIFICATION stages of injury to consider: neurapraxia, axonotmesis, and
neurobnesis (Table 4-4).269.270
Seddon's Classification Neurapraxia. The term neurapraxia is used to designate a
In order to intelligently communicate about nerve injuries, it mild degree of neural insult that results in impulse conduction
is appropriate to define a classification based on the amount of failure across the affected segment. It is also acceptable to simply
designate this type of neural insult as conduction block. The
Table 4·3. Human Polyneuropathies with Segmental
most important aspect of conduction block is its reversibility.
Demyelination
When conduction block affects a neural segment, the conducting
properties of the nerve above and below the lesion site are
Minimal Demyelination Significant Demyelination normal. Additionally, the continuity between the cell body and
Alcohol with related thiamin Diphtheria end organ is maintained. Wallerian degeneration does not result
deficiency Some forms of diabetic neuropathy from a conduction block, which implies axonal continuity.
Majority of toxic substances Some forms of Charcot-Marie- Investigators have mimicked this type of neural lesion by care
Acute porphyria Tooth disease (CMT I. CMT 4) fully compressing nerves to various degrees such that only a focal
Most paraneoplastic neuropathies Leukodystrophies demyelination occurs with little, if any. axonal injury.65.218 The
CMT2 Guillain-Barre syndrome end result of a local demyelinating lesion is action potential slow
AmylOid neuropathy Chronic inflammatory demyelinat ing and failure across the compressed aspect of nerve. Nerve con
Most diabetic neuropathies ing polyradiculoneuropathy duction is preserved proximally and distally to the lesion.
Uremic neuropathy Multifocal motor neuropathy In the above-noted compression injury, conduction again re
Ischemic neuropathies Neuropathies associated with turns within several weeks or months. i.e., the time required to
IgM (anti.MAG) monoclonal remyelinate the damaged neural segment. The large myelinated
gammopathies fibers are more susceptible to compression and ischemia than
Modified from Gilliatt RW: Recent advances in the pathophysiology of nerve
are the thinly myelinated and unmyelinated fibers. Conduction
conduction.ln:Desmedt JE (ed): New Developments in Electromyography and block usually affects motor fibers rather profoundly. with rela
Clinical Neurophysiology. Basel. Karger, 1973. pp l-18. tive degrees of sensory and sympathetic fiber sparing depending
124 - PART 1 FUNDAMENTAL PRINCIPLES
upon the degree of insult. Motor paralysis in conduction block block because muscle innervation is maintained, and secondly,
lesions typically lasts from 1 to 6 months, although most lesions recovery is typically rapid enough to avoid disuse atrophy.
usually resolve by 3 months.259.269,218 If sensation is affected. it Fibrillation potentials should not be observed in conduction
appears that touch perception is more profoundly altered than block as the axon is not disrupted. It is important to keep in
pain sensation. These two sensory modalities are less affected mind that a mixed lesion can exist where there is a combination
than motor control and proprioception, and return to a func of conduction block and axonal loss. In this case, it is certainly
tional status more quickly. Sympathetic fibers are the least af possible to observe fibrillation potentials,
fected by conduction block. Cutaneous sensibility is usually Conduction block is familiar to most individuals. For exam
only mildly affected and returns to normal relatively ple, sitting with one's legs crossed, such that the knee of one leg
rapidly.259,290 The severity of conduction block has been graded compresses the peroneal nerve for several minutes, results in the
according to the duration of the block: (1) brief; lasting minutes foot "falling asleep." This sensation corresponds to an ischemic
to hours, (2) moderate; blockage for up to 4 weeks, and (3) insult of minor degree to the peroneal nerve with a resultant
severe; several months duration (Table 4_4).282 Unfortunately, it conduction block. Depriving the nerve of its needed blood
is not possible to accurately grade the severity of conduction supply impedes action potential propagation across the is
block prior to it manifesting resolution. chemic segment. If the compression is of sufficient degree or
Clinically, the onset of motor control and sensory functional length of time, then the individual not only can no longer acti
loss can be either abrupt or graduaL Depending upon the degree vate the foot and toe dorsiflexorsJextensors, bUl a lack of sensa
of injury, it is possible to have only partial or complete disrup tion is present as welL The conduction block prevents both
tion of either motor or sensory modalities. This variability of motor impulses from reaching the peroneal-innervated skeletal
motor/sensory loss is believed to reside in the fact that the dif muscles as well as sensory impulses from the superficial sen
ferent fibers are more or less susceptible to injury depending sory peroneal nerve reaching the cerebral cortex. Uncrossing
upon their location within the nerve as well as focal nature of the legs allows blood flow to once again return to that segment
the lesion. Muscle wasting usually does not occur in conduction of compressed nerve with eventual return of both motor and
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 125
sensory function. Prolonged compression can eventually lead to tissue is minimized to afford easy axonal growth across the
focal demyelination and, if severe enough, axonal disruption injury site.
with secondary Wallerian degeneration. One can easily see that
the manner in which nerves respond to trauma is dependent Sunderland's Classification
upon the degree of the initial or continuing insult. A second popular and somewhat more detailed classification
Axonotmesis. The second degree of neural insult in Sed was initially proposed and subsequently modified by
don's classification is axonotmesis (Table 4_4).269.270 Axonot Sunderland (Table 4_4).280.281 This classification of nerve injury
mesis is a specific type of nerve injury in which only the axon is is based upon the results of trauma with respect to the axon and
physically disrupted, while the enveloping perineurium and its supporting connective tissue structures. Sunderland's classi
epineurium are preserved. Compression of a profound nature or fication is divided into five types of injury and depends exclu
traction on the nerve are the typical etiologies of such a lesion. sively upon which connective tissue components are disrupted
Once the axon has been disrupted, the characteristic changes (Fig. 4-6).
previously described for Wallerian degeneration occur. Type 1 Injury. Type 1 injury corresponds to Seddon's des
Recovery of function is directly dependent upon the time re ignation of neurapraxia.
quired for the process of Wallerian degeneration and neural re Type 2 Injury. Seddon's axonotmesis is subdivided into
generation to eventually reach the previously denervated motor three forms of neural insult (types 2-4). A type 2 injury involves
or sensory end organ. Of course, autonomic function is also lost loss of axonal continuity with preservation of all supporting
and must be reestablished. The fact that the endoneurium re neural structures including the endoneurium and corresponds to
mains intact is a very important aspect of this type of injury. A Seddon's axonotmesis (Table 4-4). Types 3 and 4 injuries result
preserved endoneurium means that once the remnants of the de in progressively more neural disruption. Sunderland's type 5
generated nerve have been removed, the regenerating axon injury corresponds to Seddon's neurotmesis, i.e., complete
simply has to follow its original course directly back to the ap neural disruption.
propriate end organ. With this type of injury, there is no misdi Type 3 Injury. In type 3 injury there is loss of axonal conti
rection of regenerating axons. A very good prognosis, therefore, nuity as well as the endoneurium, Le., the endoneurial tube and
is implied when neural damage results only in axonotmesis, contents (axon) are disrupted (Fig. 4-6, Table 4-4). With this
provided the distance between the lesion site and end organ is
not too long.
Clinically, because the axon is physically disrupted, one can p
Endoneurium
anticipate denervation of the corresponding musculature and
~v---:==
==-"""'......"""'....,,==== ""on with
complete absence of all sensory modalities. Additionally, there 1 ========== comple,"hHth
is an absence of autonomic control to the affected area. Due to Epineurium
the process of Wallerian degeneration, all tissues become inex
citable distal to the site of injury and the proximal neural
changes previously described ensue. The length of recovery is
entirely dependent upon the distance between the level of lesion
and the end organs. Obviously, this time interval is longer than
2 ~----:-=--=-=--=--=:=::=:______________
that previously described for conduction block. With respect to
motor recovery, the previously denervated muscles demonstrate
---_.--------=
voluntary activity in the sequential order in which they are in
nervated, Le., return is proximal to distal. It is often possible to
clinically trace the nerve's recovery based on the advancing 3 __::_=_::__:::_=
.J)~'--:::::_::: __
. ~
Tinet's sign, as the sensory fibers are sensitive to percussion at
their growing tips. Although the prognosis for recovery is very
good, there are occasions when the effects of retrograde neu
ronal degeneration has resulted in the loss of some cell bodies.
In this instance, less than complete recovery can be expected.
Neurotmesis. The greatest degree of disruption a nerve can
4 ~,~(l::::::__:_::__:_:__::-::_-_:-.:...~-
incur is designated neurotmesis and implies complete disrup -: - : --:. -
tion of not only the axon, but all supporting connective tissue
structures. 269 ,270 In this instance not only is the axon disrupted, ~
---- - -.-:::-
but the endoneurium, perineurium, and epineurium are no
longer in continuity. Neurotmesis implies the nerve is com
pletely severed even if the outward gross appearance suggests
5 ~';::~-~-~--~-
type of injury, Wallerian degeneration is to be expected as well face widespread loss of continuity and misalignment of en
as a loss of organization within the funiculus. The perineurium doneurial tubes. Additionally, because of the internal architec
and epineurium remain intact. Unfortunately, the intrafunicular tural disorganization, regenerating axons now not only enter
disorganization and hemorrhage, edema, and fibrosis tend to inappropriate endoneurial tubes, but also penetrate between fu
retard optimal neural regeneration to the original end organs. niculi to end blindly in supporting connective tissues. It is likely
Traction and compression are common etiologies for this type that many fourth-degree injuries lead to neuroma formation .be
of neural insult. cause of the above-noted mass of misdirected axons and con
Neural recovery in third-degree injuries is usually less than nective tissue proliferation. The clinical recovery of these types
optimal. Because of this injury's severity, it is to be anticipated of injuries is rather poor and often requires surgical intervention
that a number of sensory and motor neurons are lost. This loss to reduce the internal disorganization and scar tissue.
of proximal nerve cells results in a reduced number ofaxons ca Type 5 Injury. In fifth-degree injuries, the entire nerve is
pable of participating in the regenerative process. Additionally, disrupted such that there is a loss of continuity, Le., the nerve is
the entire neural recovery process is hindered and delayed be severed through all of its supporting connective tissue structures
cause of the necessary recovery time for the nerve cell bodies (Fig. 4-6, Table 4-4). The epineurium has been completely tran
that have undergone the axonal reaction. Some of these cell sected. Profound Wallerian degeneration as well as the proximal
bodies may not recover fully following the traumatic incident. A axonal reaction develop. Any functional recovery is rather rare
second impediment to maximal recovery is the intrafunicular in this type of injury. The severe axonal reaction suggests that
disorganization and scarring. Fibrosis and edema may reduce the number of surviving proximal cell bodies is significantly re
the neurites' ability to traverse the injury site. The third major duced. Also, very few of the axons capable of regeneration can
factor limiting recovery is the misalignment of endoneurial find appropriate endoneurial tubes to enter because of the phys
tubes. Axons that do recover sufficiently to penetrate the intra ical separation between the cut nerve ends and profound en
funicular disorganization may not be able to relocate their origi doneural tube misalignment. It is highly likely that the trauma
nal or similar end organ endoneurial tubes. Successful producing the injury will lead to significant scarring, thereby
regeneration across the lesion, therefore, is functionally useless further impeding any axonal regrowth through the injured area.
because of end organ misdirection. Even in the face of excellent surgical repair, the prognosis for
The importance of endoneurial tubes misalignment has optimal functional recovery is limited.
varied consequences depending upon whether the funiculus in
volved is comprised of different types of fibers or all of the NEUROPHYSIOLOGIC CORRELATES OF NERVE INJURY
same fiber type traveling to the same end organ. For example, if
a funiculus contains only motor fibers traveling to foot plantar Following either nerve crush or section, it is important for the
flexors, misdirection of different axons within this funiculus has practitioner to be aware of what can be anticipated with respect
minimal clinical consequences. The foot will still respond to the to neural conduction. The electrophysiologic correlates to
command of plantar flexion. On the other hand, if a funiculus Wallerian degeneration are primarily investigated in animal
contained motor fibers traveling to muscles with different func models, but nevertheless have direct bearing on what is occur
tions as well as cutaneous sensory fibers, misdirection ofaxons ring in humans following nerve injury. Additionally, pertinent
down inappropriate endoneurial tubes can have disastrous clini findings regarding terminal axon and neuromuscular junction
cal implications. alterations are also noted.
Recovery time in third-degree injuries is longer than that de
scribed for second-degree injuries primarily resulting from the Neural Crush
axonal reaction of the cell bodies combined with the internal fu As previously noted, the importance of crushing a nerve is
nicular disruption. Unlike second-degree injuries, the clinical that the endoneuria! tubes remain intact even though significant
recovery of motor and sensory function is expectedly less. Also, Wallerian degeneration can occur distal to the injury site. This
muscles that have been denervated longer require more time to affords the nerve the possibility of a complete return to their re
respond and subsequently recover from denervation. It may be spective end organs. Given that a patient may achieve satisfac
difficult for reinnervation to occur in the muscle secondary to tory function following reinnervation, it is of interest to examine
intervening connective tissue or fibrous muscle tissue impeding the physiologic status of neural conduction both above and
collateral sprouting. Of importance in third-degree injuries is below the crush site.
the reduced value of the Tinel's sign to demarcate the advancing Once a nerve has been sufficiently crushed to induce
progression of recovery. This is because sensory axons may Wallerian degeneration, one can first explore the effects of the
have been misdirected into inappropriate endoneurial tubes. injury on proximal nerve conduction velocity and the histologic
Thus, there may be a steady advance of the Tinel's sign but this correlates of the nerve damage. That portion of nerve proximal
is to no avail as it may be heading distally in an endoneurial to the lesion demonstrates a reduction in conduction velocity to
tube destined to end in muscle. approximately 90% of normal within 30 days of the injury.3.57,80
Type 4 Injury. The significance of the fourth-degree By 100 days, the conduction velocity has been further reduced
injury is disruption of the perineurium (Fig. 4-6, Table 4-4). to 80% of its preinjury value. This 80% value is maintained
Wallerian degeneration and loss of neuronal cell bodies occur. until about 150 days after neural trauma and then progressively
Disruption of the perineurium results in massive disorganiza increases to normal within the next 50 days, Le., 200 days fol
tion of the internal structure of the peripheral nerve trunk with lowing the original insult. These findings occur only if the re
significant hemorrhage, edema, and reactive connective tissue generating nerve below the injury site rejoins its appropriate end
proliferation involving multiple nerve fibers. This disorganiza organ. Should there be failure to re-establish peripheral continu
tion combined with the results of trauma lead to significant scar ity, the proximal nerve conduction velocity falls to about
formation. Those axons, which eventually recover sufficiently 60-70% of the original velocity and does not improve above
to attempt regrowth, must penetrate substantial scar tissue and this level even when followed for a period of 400 days.129,170 It
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 127
appears that even though a significant portion of the injured can be exemplified by a simple example. Let us assume that a
nerve may be spared proximal to the injury, it nevertheless ex 10-cm segment of nerve has been affected by some disease
periences a reduction in conduction velocity. The slowing of process that has resulted in thinning of the myelin sheath pro
proximal nerve conduction is explained if one considers the his ducing an internodal conduction time of 100 J.ls. We know that
tologic consequences of distal nerve injuries on the more proxi the normal internodal conduction time is roughly 20 J.ls, yield
mal portions of the same nerve. ing a conduction over the 10 cm segment of 50 mls (20 Ilsll
Within the first 150 days after nerve injury, the axonal diame node x 100 mm x 1 nodell mm =2 ms; NCV = 1oo mml2 ms =
ter of the proximal nerves demonstrates an 8.9% reduction in 50 mlS).246 A conduction time of 100 J.ls/node results in a con
size while the total fiber diameter diminishes by 5.3%.51 The duction velocity of 10 mls (100 Ilsll node x 100 mm x 1 nodell
myelin sheath, however, appears to increase in thickness by ap mm = 10 ms; NCV = 100 mmllO ms = 10 mls). On the other
proximately 5.9%. After 150 days, the axon diameter and total hand, if the damaged myelin is removed and matures with twice
fiber diameter begin to increase so that by 225 days the injured as many nodes of Ranvier and there is restitution of the nodal
and non injured side are of comparable diameters. There is cer and paranodal regions, a less than normal neural conduction is
tainly a correlation between fiber diameter and conduction ve also noted. The conduction velocity over the repaired segment
locity in both normal and the injured nerves. Within the first 150 is expected to approach 25 mls (20 J.lsll node x 100 mm x 2
days, both conduction velocity and axon diameter decrease. nodes/l mm = 4 ms; NCV = loo mml4 ms = 25 mls). Note that
After 150 days, axon diameter returns to normal as does nerve the thinning of myelin produces an 80% reduction in conduc
conduction velocity. tion velocity compared to a 50% reduction resulting from an in
Interestingly, following both crush injuries and nerve section, creased number of internodes. The alteration in myelin
the internodal length of the regenerated portion of nerve distal thickness can have a much more profound effect on neural con
to the injury is shortened compared to normal. The normal in duction than increasing the number of nodes. This is observed
ternodal distance in large myelinated nerve fibers is roughly be experimentally in regenerated nerves where the conduction ve
tween 0.83 mm and 1.3 mm. 154,295 Following reconstitution of locity approaches the normal conduction velocity.262 This return
the peripheral nerve distal to the injury, the average internodal of almost normal conduction may be the result of an optimiza
length is approximately 300 J.lm, Le" roughly a 2:1 or 3:1 ratio tion of the internodal length (reduced) and the regenerating
compared to normal nerve. The internodal distance of 300 J.Iffi is nerve's diameter (also reduced).33 Of course, during the re
similar to that noted in developing animals when the Schwann myelination process, there is likely to be a combination of both
cells first appear. The Schwann cells are believed to elongate an increased number of internodes and a rather thin myelin
with limb growth to achieve their adult length. 172,295 In regenera sheath producing rather profound reductions in conduction ve
tion of the injured adult nerve, limb growth has ceased and sub locity. In our example, the NCV would be reduced to 5 mls
sequently the normal separation of Schwann cells of 300 J.lm is during myelin regeneration if at some point there was a dou
re-established, thus accounting for the reduced internodal dis bling in the number of nodes with an internodal conduction time
tance. It appears, therefore, that in regenerating nerves, the in of 100 J.ls. These are of course only theoretical considerations as
ternodal distance is less important than axonal diameter in little controlled long-term information is available regarding
determining nerve conduction veiocity.33,262,305 human neural conduction during and after regeneration.
Distal to the site of injury, there is a significant difference in
the eventual conduction velocity compared to the proximal neural Neural Section
segment. The distal conduction velocity eventually reaches ap Sectioning a nerve leads to somewhat different results than
proximately 60-90% of the preinjury value,l1·59,9Q,145,155,171,172 those noted above, particularly when the proximal portion is ex
Studies in excess of one year fail to demonstrate complete re amined. Maximum conduction velocities reached in the proxi
covery of the nerve conduction velocity to normal values. The mal portion of nerves following sectioning and subsequent
primary explanation of this finding is most likely found in the regeneration approached 60-70% of normal, which is consider
histologic observations of these nerves following regenera ably less than the 90% or more previously noted.57 The reduc
tion.l44 Comparison of injured neural diameters with the control tion in velocity is most likely the result of the affected nerves
or noninjured side reveals that there is a distal tapering of the proximal to the transection failing to regain their preinjury di
nerve, Although the diameter of the nerve within a few centime ameter. 8U26 The profound nature of the insult also may lead to
ters of the injury site is similar to the size of the contralateral significant losses of motor and sensory neurons reducing the
control nerves for that level, the regenerated nerve gradually population of fastest-conducting fibers,
loses size distal to the injury. This axonal atrophy is most likely Assessing nerve conduction velocity distal to the site of nerve
a result of Wallerian degeneration, because as previously de severance reveals that less than 80% of the normal velocity is
scribed, the endoneurial tube undergoes a considerable reduc attained even at follow-up times greater than 3 years. IS
tion in size. There is an obvious failure of the regenerated nerve Histologic examination of the nerve fiber diameters reveals an
to completely re-expand the endoneurial tube. As nerve conduc interesting finding. Crushing the nerves permits an almost
tion velocity is directly proportional to neural diameter, it is not normal fiber size distribution with a bimodal peak of large and
surprising that the smaller regenerated nerves conduct at slower small fibers. The fiber size distribution after cutting a nerve pri
velocities than noninjured nerves. This reduction in velocity, marily reveals a large number of small fibers with a signifi
however, should have little effect on the observed clinical out cantly reduced popUlation of larger-size nerves. The reduction
come. Complete clinical recovery is expected given that the en in size is particularly important because the myelin thickness
doneurial tubes maintained their continuity and there is no remains thinner than normal, which may account for the re
misdirection or failure of nerve regrowth, Also, strength is not duced conduction velocity.267 The reduction in fiber diameter,
dependent on conduction velocity. therefore, most likely results in the failure of a sectioned nerve
The effects on conduction velocity of an increased number of to regain normal conduction velocities. As previously stated; an
nodes following myelin replacement compared to demyelination increased number of internodes also contributes to the amount
128 - PART I FUNDAMENTAL PRINCIPLES
of time necessary to convey an action potential over the same rate. It appears that the small myelinated fibers experience the
distance of nerve. above noted sequence of breakdown slightly ahead of the larger
myelinated fibers. Once failure of action potential propagation
DYNAMIC ELECTROPHYSIOLOGIC OBSERVATIONS is noted, there is clearly observed to be axonal fragmentation of
OFWAllERIAN DEGENERATION all fiber sizes. In this sense, failure of neural conduction is cor
related with loss of axonal continuity, i.e., once the axon is frag
The previous sections have considered the somewhat static mented, action potential propagation ceases. Also, the failure of
consequences of Wallerian degeneration and regeneration with conduction occurs along the entire nerve length simultaneously.
respect to the eventual clinical correlation to nerve conduction Of scientific interest is the issue of whether or not Wallerian
velocity. Of equal interest is the dynamic failure of both neural degeneration and consequently loss of neural excitability
action potentials and neuromuscular transmission immediately progress in a proximal to distal direction from the site of injury.
following nerve injury. To simplify these observations, the ma Sectioning a rabbit sciatic nerve and stimulating the nerve at
jority of investigators have used complete nerve section. The two sites distal to the lesion, near and far from the section, while
technique used to assess the evolution of conduction failure in recording the ensuing nerve action potential clearly reveals that
the animal model is to completely severe a selected nerve and the action potential persists longer from the distal stimulus
then activate the distal portion of this cut nerve recording both site. 48 Specifically, by 40-48 hours the proximal nerve action
nerv~ action potentials and compound muscle action potentials. potential is markedly decreased by about 70% while that arising
At selected times, the nerves are removed from a few of the ani from distal stimulation is significantly larger. The same rela
mals so that correlative histologic sections of the nerve can be tionship is noted 60 hours following neural section. By 72
made with the electrophysiologic findings. For obvious reasons, hours, both potentials have become difficult to evaluate. This
our knowledge regarding this electrophysiologic and histologic suggests that degeneration is proceeding toward the periphery
relationship is lacking in humans. The information gained from from the lesion site. 230.257 Histologic evaluation of these nerves
mammalian species is nevertheless of clinical relevance and will reveals that coincident with failure of conduction along the
be related to what limited information is available in humans. nerve is a progression of myelin retraction from the nodes of
Ranvier. 46.47 Early conduction failure (40 hours) as evidenced by
Nerve Action Potentials nerve action potential amplitude reduction (compared to the
A detailed investigation performed in rabbits allows us to ap previously noted loss of conduction at 70 hours) is proposed to
preciate the clinical findings following a nerve injury based be the result of the paranodal retraction of myelin leading to
upon the interdependence between the morphologic results of action potential failure at the widened nodes. Subsequent histo
Wallerian degeneration and the electrophysiologic conse logic investigations have failed to substantiate the centrifugal
quences of nerve breakdown. Within the first 24 hours, the direction of Wallerian degeneration and this subject remains un
nerve's conduction velocity as measured directly from nerve settled. 71 It is certainly conceivable that there may be a combi
action potentials, and thus ignoring the muscle's response, is es nation of failure at the nodes of Ranvier prior to axonal
sentially unchanged. 128 The nerve fibers demonstrate little, if fragmentation depending upon the progress of degeneration in
any, alteration in structure. At 40 hours, the nerve conduction different size fibers of a given nerve and possibly different
velocity continues to be greater than 95% of normal, but the nerves in the same and other animal species.
nerve fibers are beginning to demonstrate irregular outlines and
diffuse swellings. Of importance, however, is that the axon is Nerve·to·Muscie Transmission Failure
still intact as a thin and continuous band of axoplasm can be ob In addition to action potential propagation cessation, it is also
served. By 48 hours, neural conduction velocity is approxi necessary to consider neural transmission in the terminal axons
mately 95% of normal and neural continuity continues to be and electrochemical conduction across the neuromuscular junc
preserved. Observation 60 hours after nerve section reveals the tion following Wallerian degeneration. These processes can be
conduction velocity to be slightly less than 95% of normal, easily examined if similar methodologies to those noted above
while the nerve demonstrates some myelin retraction at the are repeated with the addition of simultaneously recording both
nodes of Ranvier. Axonal continuity is still maintained in all but nerve action potentials and compound muscle action potentials
a few of the smaller-diameter axons that are undergoing frag from nerve and muscle innervated by the sectioned nerve, re
mentation. At 70 hours, the conduction velocity is approaching spectively. Again, it is impossible to perform these investiga
80% of normal and the amplitudes of nerve action potentials are tions in humans; however, subhuman primates (e.g., baboons)
decreasing. The myelin sheath is rather swollen, but ovoids are have been studied and the results most likely parallel what is oc
not yet observed and there is an increase in the amount of curring in humans following nerve section. 107 When recording
axonal fragmentation. Seventy-two hours after neural section, from the muscle innervated by a sectioned nerve, there is a re
the nerve is no longer excitable (i.e., there is an absent response duction in the compound muscle action potential's amplitude by
to electrical stimulation). Histologically, the nerve demonstrates about 21 % at 48 hours after nerve section when stimulating
axonal swellings with significant fragmentation ofaxons, al close to the recording site. Four days after the insult, the ampli
though a few are still observed to be intact. Most of the frag tude drops to only 3% of the control value. By 6 days, a muscle
mentation is noted to first occur at the nodes of Ranvier. The response could no longer be observed in any of the experimen
myelin, however, appears intact at this time despite significant tal animals. When the same nerve is excited at a more proximal
paranodal retraction. Digestion of myelin along with axonal level, the same results are observed. The significance of this
fragments is well underway by 86 hours and the classic descrip finding is that failure of the motor response occurs below
tion ofWallerian degeneration is noted (see above). (closer to the muscle) the distal point of stimulation, i.e., in the
Several additional observations are of importance during collateral axons within the muscle or at the neuromuscular junc
Wallerian degeneration. During this process, it is clear that not tion. When the nerve conduction velocities and distal motor la
all of the myelinated fibers undergo degeneration at the same tencies are examined, it is noted that both parameters essentially
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 129
maintain their original values until the response is almost com Table 4·5. Conduction Failure Distal to Nerve Section
pletely absent. In other words, there is preservation of the Failure Time
fastest-conducting nerve fibers until the time of complete re Nerve
sponse failure.
Neural Action Potential Failure
In the above study, the nerve action potentials persist approx
Rabbit l28 Peroneal 71-78
imately 3 days longer than the muscle responses. All electrical
activity had ceased from muscle tissue by day 6, while ascend Rat l28 Peroneal 79-81
ing nerve action potentials could be recorded until day 9. Both Guinea pig l28 Peroneal 72-82
latency and conduction velocity of the nerve potentials re Cat1S7 Sciatic 72-101
Dot<> Phrenic 96
mained unchanged from the control data until complete failure
Baboon 107 Lateral popliteal 120-216
of action potential propagation occurred. These findings sub Human5I,2l4,JI7-JI9 Median, radial 168-264
stantiate the previous preservation of motor conduction until the
response has completely disappeared. Histologic observation of Sensory
the same nerves at 3 days revealed that the main nerve trunk Musde Activation Failure
only demonstrated an irregular myelin contour, especially about Rabbit l29 Peroneal 30-32
the paranodal regions. However, there was no widening about RatIOS Sciatic 24-36
the nodes of Ranvier. Importantly, the intramuscular terminal Guinea pigl60 Sciatic 40-45
axons demonstrated profound myelin fragmentation, particu Cat l91 Sciatic 69-79
larly near the neuromuscular junction. In a number of speci Baboon 107 Lateral popliteal 96-144
mens, there was complete absence of the axon's terminal Human5I,I04.123.234,317-J'9 Facial, median, ulnar 120-216
portion. Within 6 days, the more proximal portions of the nerves Motor
in the leg revealed axonal fragmentation while there was no
trace of the terminal axons within the muscle. There is clear ev
idence in this preparation to substantiate the previous finding days.53,104,I60,234,317.318.319 There is a lag of about 2-3 days for the
that neuromuscular transmission fails prior to action potential sensory response. There is noticeable amplitude loss between
propagation in the proximal portions of the injured nerve days 5 and 7 with disappearance of the sensory response by day
trunk. 23 ,127,189,191,197,205,215,261 10 or 11. A complicating factor regarding the interpretation of
There are several additional points of interest regarding mus side-to-side amplitude comparisons is the inherent variability of
cular activation during Wallerian degeneration. During investi normal physiologic differences. This parameter has been poorly
gations of the time delay between loss of neural propagation documented and is assumed to be minimal, but in the author's
and muscle activation, there was noted to be a length-dependent experience may reach 30% or more. Further normal side-to-side
relationship between the distance separating the nerve's transec amplitude ranges need to be recorded prior to fully using the
tion site and the muscle and how long it took for loss of muscle above information.
excitation from neural stimulation. The longer the section of Consideration of the above information explains the typical
nerve between neural section and muscle, the greater amount of observation of obtaining evoked sensory responses for several
time was noted for inducing an action potential in the muscle. more days than the compound muscle action potential (CMAP).
For any given length of transected nerve, there is an additional It is noted that the motor nerve continues to conduct an impulse
45-minute delay between cutting the nerve and that nerve losing even though the neuromuscular junction disintegrates. A poten
the ability to generate a muscle action potential for each addi tial can be recorded directly from the motor nerve even though
tional centimeter of length.205 In other words, terminal intramus the CMAP may be absent on day 7. This direct motor nerve po
cular axonal destruction is delayed by 45 minutes per every tential persists until about day 10, which is similar to that for the
additional centimeter of axon length added proximal to the sensory nerve. A sensory potential, therefore, can be recorded
lesion site. The exact reason for this length-dependent sparing is for several more days after the CMAP response is absent be
unknown but is postulated to be secondary to a "trophic" influ cause the technique for recording sensory potentials is one of
ence of some material present in the axon that is transported to essentially a direct nerve response, whereas the motor technique
the periphery. This additional time appears to be related to the relies upon an intact neuromuscular junction.
velocity of fast axonal transport of some unidentified substance. From the above discussion it is evident that a proper classifi
There is an obvious species difference regarding failure of cation of nerve injuries is very important. The distinction be
action potential propagation in a nerve undergoing Wallerian tween conduction block and Wallerian degeneration may well
degeneration compared to failure of muscle activation (Table 4 be made using electrodiagnostic studies. Classifying a nerve
5). Non-primate species appear to demonstrate preservation of lesion in minimal or intermediate versus severe (Table 4-1), or
nerve action potential propagation between 71-96 hours, in Sunderland's classification between type 1 or type 2 and
whereas primates maintain neural propagation for a time period higher is typically done with the aid of neurophysiologic tech
approximating 120-264 hours, with humans at the longer aspect niques. However, the distinction between axonotrnesis and neu
of the time spectrum. Loss of muscle excitability due to disinte rotmesis is an anatomic definition and can never be made on
gration of the intramuscular terminal axons and neuromuscular neurophysiologic grounds. A well-performed classification of
junctions occurs between 30-79 hours in lower mammals. The nerve injuries is thus the result of combining electrophysiologic
same time frame in primates extends to 96-216 hours again data with the clinical context.
with humans taking the most time to demonstrate absence of
muscle activation. Following complete section of a nerve in CLINICAL CORRELATION
man, therefore, one can anticipate loss of the motor response
amplitude to begin by the third to fifth day with absence of a The above findings primarily noted in animal studies are of
compound muscle action potential between the seventh to ninth particular relevance to the investigation of human nerve lesions.
130 - PART 1 FUNDAMENTAL PRINCIPLES
It is important to keep in mind the sequence of events with respect Rest Activity
to loss of motor and sensory evoked potentials to avoid an erro Muscle PSW!Fibrillation Recruitment
neous diagnosis. An illustrative case may help one to conceptualize (R)APB 0 Normal
the various aspects of a nerve transection regarding electrophysio (R) Pronator teres 0 Normal
logic findings and the appropriate conclusions to be drawn. (R) Flexor carpi radialis 0 Normal
(R) Extensor digitorum 0 Normal
Case Example (R) First dorsal interosseous
History. A 26-year-old male construction worker sustained (day 2) 0 Absent
a severe blow and laceration to the medial aspect of the right (day 12) 0 Absent
forearm just distal to the medial epicondyle. He complained of (day 15) 2+ Absent
sensation loss along the medial aspect of the affected hand to in (R) Abductor digiti minimi
clude the fourth and fifth digits immediately following the (day 2) 0 Absent
injury. The patient also complained of difficulty forming a (day 12) 0 Absent
strong grip in the right hand. He denied any previous medical (day 15) 2+ Absent
problems or medication consumption, and had been in a state of (R) Flexor carpi ulnaris
good health prior to the accident. (day 2) 0 Absent
Physical Examination. The patient was examined within 18 (day 12) 1+ Absent
hours of the injury. There is noted to be a complete absence of (day 15) 2+ Absent
sensation to all modalities (touch, pin prick, vibration, and pro
prioception) in the distribution of the ulnar nerve in the right Surgical Exploration. Surgical exploration 4 weeks follow
hand to include the volar and dorsal aspects of the fourth and ing injury revealed a complete laceration of the ulnar nerve in
fifth digits as well as the dorsum of the hand. Manual muscle the postcondylar groove.
testing of the hand intrinsic muscles innervated by the ulnar
nerve found them to be 0/5 (adductor pollicis, first dorsal in Comment
terosseous, abductor digiti minimi, opponens digiti) while the There are a number of clinically relevant aspects to the
median-innervated muscles were 4/5. The flexor digitorum pro above-noted electrophysioiogic portion of the electrodiagnostic
fundus to the fourth and fifth digits 0/5. All remaining muscles medicine consultation. If the patient had been examined within
of the right upper limb were 5/5 and the sensation to the remain the first 4 days following injury, the ulnar CMAP amplitude
der of the hand was normal. Deep tendon reflexes to the biceps would have been normal following stimulation at the wrist, but
brachii, triceps, pronator teres, and brachioradialis was 2+12+. CMAPs would not have been obtainable following stimulation
There was noted to be clawing of the fourth and fifth fmgers. proximal to the lesion site. In addition, electromyography
Nerve Conduction Studies. Nerve conduction studies were would reveal no recruitable motor unit action potentials in the
performed in the upper limbss bilaterally. The mid-palm tem ulnar-innervated hand intrinsic muscles. It is impossible at this
perature was 32.5°C on the right and 33.0°C on the left. point to assess whether there is a partial or complete transection
of the ulnar nerve with a component of conduction block or if
DSL S Amp DML M Amp NCV
Nerve (ms) (PV) (ms) (mV) (m/s) there is a profound conduction block with minimal axonal
injury. If there had been an inability for neural conduction to
Right median 3.1 50.0 3.5 7.0 60.0 propagate across the injury site because of a conduction block
Right ulnar (below injury) (neurapraxia), the findings on days 2-4 would be anticipated.
(day 2) 3.0 20.0 2.9 6.0 62.0 The decreased ulnar motor amplitude to less than 50% of the
(day 4) 3.0 20.0 3.0 2.9 61.0 contralateral side on day 4, however, is suggestive of an axonal
(day 6) 3.2 18.0 3.2 1.2 58.0 injury.84,92,15S There is no confirmatory evidence of a specific
(-day 8) 3.4 10.0 Absent type of injury on needle electromyography at this point. The
(day 10) 3.5 6.0 Absent sensory studies are essentially normal and complimentary to the
(day 12) Absent Absent unaffected side. Note that the distal motor latency and nerve
conduction velocity are well within acceptable normal values.
Right ulnar nerve (above injury)
(day 2-12) Absent By day 6, the amplitude of the ulnar motor response to stimu
Absent
lation below the injury is now clearly abnormal and certainly
Right radial 2.9 25.0 2.1 5.0 72.0 implies that there has been a profound injury to the motor fibers.
Left ulnar 2.9 22.0 3.0 8.0 62.0 Note that the distal motor latency and nerve conduction velocity
are stilI well preserved. Again, the sensory response appears
Left median 3.2 45.0 3.3 8.5 58.0
quite normal and one may believe that the patient has only sus
DSL, distal sensory latency; S Amp, sensory amplitude; tained a partial nerve injury with sparing of the sensory fibers.
DML, distal motor latency; M Amp, motor amplitude; NCV, On day 8, there is no longer an obtainable motor response for
nerve conduction velocity; ms, milliseconds; flV, microvolts; the affected ulnar nerve. The distal motor latency and conduc
mV, millivolts; mis, meter/second. Motor and sensory ampli tion velocity were quite acceptable until the response was no
tudes are measured baseline-to-peak. Sensory latencies are mea longer detectable. As noted previously, this implies that there
sured to peak while motor latencies are measured to initial was sparing of the large and fast-conducting fibers until the
negative onset. compound muscle action potential completely disappeared.
Recall from the previous section that the reason for this obser
Needle Electromyography. A needle electromyographic in vation is most likely a result of disintegration and fragmentation
vestigation was performed on the left upper limb using a dispos of the terminal intramuscular axon branches and neuromuscular
able monopoiar needle. junctions. It appears that humans undergo phases of neural
Chapter" PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 131
response to injury similar to the lower primates. Remember that illustrates what can be expected once a patient has sustained a
the main trunk of the nerve is still excitable. This can be demon peripheraJ nerve injury. Examining the patient too early can lead
strated by performing a mixed nerve response of the ulnar to a misdiagnosis. As noted above. there is usually useful infor
nerve. Activating the ulnar nerve at the wrist and recording from mation to be gained by day 10, but the most complete data can
just below the injury would have yielded a small but detectable be gathered by about day 15. Of course, the surgeon may wish
mixed nerve response. If the ulnar nerve had been injured just to acquire neurophysiologic data prior to that time and this is
above the wrist instead of the elbow, it is highly likely that the certainly acceptable provided the practitioner is aware of what
drop in motor amplitude would have been noticed several days the gathered data means with respect to the natural progression
earlier. Recall that the preservation of the evoked motor re ofWallerian degeneration and the electrophysiologic manifesta
sponse is dependent upon the length of nerve between the site tions at each stage of neural disintegration.
of severance and the muscle.
Beginning on day 8 and beyond, the ulnar sensory response
now displays a drop in amplitude compared to the unaffected MINIMAL NEURAL INJURY
side. The sensory latency remains normal, however, and sug
gests that there is preservation of the large and fast-conducting The term minimal injury is used in the context of an insult to
fibers. This response persists beyond that of the motor because the peripheral nervous system that produces a temporary and
of a lack of a neuromuscular junction. We are recording a nerve completely reversible failure of action potential propagation
action potential, which is known to last several days longer than over a well localized neural segment (Table 4-1). It is to be un
the motor response because of the previously noted destruction derstood that there are no structural alterations in the axon, en
in the terminal muscular axons. veloping myelin sheath, or supporting connective tissue
Within the first 12-15 days, the needle electromyographic ex structures. Once the insult is removed, there is a relatively rapid
amination only reveals abnormally decreased recruitment. This return of neural function to the preinjury condition with normal
finding is certainly consistent with either a complete conduction clinical function.
block, partial axonal loss and profound conduction block, or The term conduction block refers to the inability of an action
complete axonal transection. The presence of membrane insta potential to propagate beyond a specific region of nerve. Neural
bility is only manifest quite some time after the nerve conduc conduction can fail for a number of reasons. Following nerve
tion studies have clearly demonstrated a profound abnormality. transection, an action potential is incapable of conducting
It is certainly important to find signs of muscular denervation. If across the transected nerve (see Wallerian Degeneration). If a
the motor and sensory nerve conduction studies had remained traumatic insult to a nerve over a particular location is of suffi
normal through day 15 and beyond with respect to amplitude cient force to result in disruption of the axon and investing
and the needle examination demonstrated continued absence of myelin sheath with distal disintegration of the axon, the nerve
membrane instability and voluntary motor units, conduction can no longer sustain action potential propagation distal to the
block is the likely conclusion. With the same nerve conduction injured site. Loss of myelin over a localized segment with com
studies but membrane instability, there is now the distinct possi plete preservation of axonal continuity can also result in action
bility of a mixed lesion with both axonal loss (probably mild potential blockade. Compression or its induced ischemia can
because of motor amplitude preservation) and conduction result in loss of action potential propagation. This is perhaps the
block. The observation of an absent or markedly reduced most familiar type of conduction block experienced by most in
CMAP amplitude to stimulation of a peripheral nerve distal to a dividuals at some point following the crossing of one's legs. It is
lesion strongly implies that there has been significant Wallerian rather easy to compress the common peroneal nerve about the
degeneration. When describing the impression of Wallerian de fibular head by crossing one leg over the other. The induced
generation, it is inappropriate to use the terms axonotmesis or compressive ischemia causes the peroneal nerve to experience
neurotmesis as these are histologic terms and not neurophysio conduction failure secondary to anoxic disruption of the meta
logic descriptions. The above electrophysiologic tests cannot bolic processes responsible for action potential propagation
distinguish between disruptions of specific supporting connec over the affected segment. Relief of the compression within sev
tive tissue structures. Both axonotrnesis and neurotrnesis appear eral minutes quickly restores the ability of the nerve to again
the same with respect to nerve conduction studies or needle conduct impulses. The clinical description of an inability to
electromyography. contract the muscles innervated distal to the site of compression
It can be seen from the above example that following an or sense cutaneous stimuli is a result of this temporary conduc
injury. the earliest sign ofWallerian degeneration is reduction in tion block. Temporary compression of a limb induced by a
the compound muscle action potential. One must be careful, sphygmomanometer cuff serves as the model to explore mini
however, as there is a wide range of normal with respect to mal neural injury and the transient effects of conduction block
motor amplitude and it is a good idea to compare the affected resulting from ischemia.
with the unaffected side. If a side-to-side amplitude difference
approaches 30-40%, it is safe to assume that the patient has sus TEMPORARY NEURAL ISCHEMIA
tained an axonal lesion provided excitation occurs below the
lesion site. A repeat study within 10-15 days is indicated to con In an attempt to quantify and simulate the clinical effects of
firm the original suspicion with an absent or reduced sensory re compressing one's peripheral nerve, a blood pressure cuff can
sponse and membrane instability on intramuscular needle be placed about an elevated arm. 103.190.315 The pressure in the cuff
examination. It is important not to be confused by the progres is then increased well above systolic blood pressure to approxi
sion of Wallerian degeneration. There is a natural sequence of mately 180 mmHg or more. The arm is then comfortably rested
events to be expected following neural transection with respect in a warm water bath and the subject is requested to describe the
to the nerve conduction and needle electromyographic portion ensuing results. Within 13--15 minutes there is noted to be a re
of the electrodiagnostic medicine consultation. The above case duction in sensation involving the tips of the fingers with the
112 - PART I FUNDAMENTAL PRINCIPLES
second and third digits affected first. The first and fourth digits while older subjects (61-82 years) reveal smaller increases in
then experience decreased ability to perceive superficial tactile duration. In addition to the above-noted parameters. sensory
stimulation. Finally, the fifth digit succumbs to the above-noted nerves also demonstrate prolongation of the refractory period
inability to detect sensation at the precompression level. By 17 and elevation of the stimulus threshold required to obtain a re
minutes, the palm of the hand no longer sustains its previous sponse. IOS Upon release of the compressive force, the amplitude
level of sensibility. Within 1-2 minutes of the hand's altered regained 75-85% of its original value within the first 2 minutes,
ability to detect tactile stimulation, the fingers are beginning to The increase subsequently diminishes such that the response re
undergo complete anesthesia with respect to touch sensation. gains its preischemic value only after 30 minutes following re
The sequence of decreased perception followed within several lease of the blood pressure cuff. The remaining parameters
minutes by total absence of tactile sensibility progresses proxi noted above were not examined in detail.
mally at a rate of 3-4 cm/minute. Approximately 30 minutes The above-noted changes in neural amplitude, velocity, and
after the initiation of arm compression, the entire limb distal to duration have been observed in single nerve fibers subjected to
the compression is anesthetic to touch, The loss of immediate anoxia. 326 The amplitude of the single-fiber spike progressively
recognition of a painful stimulus occurs within several minutes diminishes until it is no longer detectable following oxygen de
to that of tactile sensation and lags behind the advancing front privation. This continued decrement is believed to be related to
of decreased touch perception by 15-20 cm. Even after 40 min the progressive decline in the axonal resting membrane poten
utes of compression and complete absence of touch sensation, tiaL A commensurate decline in the single fiber conduction ve
pain can still be perceived, but the time of cognitive recognition locity is noted with the diminishing amplitude of the evoked
is delayed. Approximately 25 minutes of compression are re potentiaL This conduction velocity decrease results in an in
quired for motor power of the hand intrinsics to become absent creased temporal dispersion of the nerve's composite fiber ve
or profoundly decreased, This absence of motor function corre locities, thus contributing to the decline in the summated
sponds to the time of complete disappearance of touch percep potential observed, Action potential propagation can even cease
tion in the hand, By 30 minutes, the hand extrinsics are during anoxia despite the amplitude being 75% of the preanoxic
completely paralyzed, Following release of the cuff, the order value. 326 The sensory nerve action potential observed with elec
of functional recovery is the reverse. Altered touch sensation re trical excitation of the nerve during an ischemic episode is,
covers first in the arm followed by the forearm, hand, and fi therefore, the summation of single nerve fibers demonstrating
nally fingers, This process of recovery requires approximately individual responses to the ischemic conditions,
25-50 seconds for a compression time of 30-35 minutes, Histologic examination of animal nerves subjected to is
Unlike sensation, however, motor power requires about 17 min chemic conditions for periods of up to 4-6 hours at 250-300
utes to regain complete precompression strength, mmHg did not result in detectable structural damage. I'2 ,218
It is also possible to repeat the above experiment and record Neither demyelination nor axonal loss with Wallerian degenera
the sensory nerve action potentials to observe the electrophysio tion could be observed, The production of ischemia for this time
logic effects of limb ischemia. 43,45,213,271 Specifically, ortho period. however, may result in muscular and subcutaneous
dromic sensory nerve action potentials from the third digit to tissue edema secondary to alterations in capillary permeabil
wrist can be serially elicited while a cuff is inflated, maintained ity.32o,321 Ischemia approaching 8 hours can result in significant
above systolic pressure, and subsequently deflated. For individ neural injury.195
uals 30-59 years of age, there is a 3.2% decrease in nerve con
duction and a 7.3% amplitude decrement within the first 5
minutes of suprasystolic compression, At 10 minutes, a 5,9% INTERMEDIATE NEURAL INJURY
decrease in maximum conduction velocity and a 9.6% decrease
in the preischemic amplitude are observed. By 15 minutes, a An intermediate type of insult to the peripheral nervous
9.5% and 14.6% decrease in velocity and amplitUde, respec system may be defined as one in which an insult, commonly
tively, are apparent while at 20 minutes the decrease in NCV compression, is of a degree sufficient to result in failure of
and amplitude reaches 15.5% and 27.9%. Twenty-five minutes action potential propagation (conduction block) but not
of arterial occlusion generates a reduction in NCV and ampli Wallerian degeneration (Table 4-1). The patient typically com
tude of 22.2% and 50.4%, respectively, and at 30 minutes com plains of weakness and sensory loss. Recovery is relatively
parable NCV and amplitude values of 27.1 % and 66,1% rapid compared to Wallerian degeneration but somewhat longer
reduction are obtained, For the same time periods, individuals than an acute conduction block arising from a brief ischemic
10-28 years of age demonstrate reductions that are generally a episode.
few percent larger, while subjects 61-82 years of age reveal re This type of intermediate neural lesion was initially described
ductions several percent less. There is an apparent resistance of in 187689 and later referred to as neurapraxia by Seddon,269 The
older persons' nerves to ischemia. Compared to digit-to-wrist, pathologic basis of this neural insult became apparent when his
wrist-to-elbow sensory conduction velocities demonstrate larger tologic investigations of nerves subjected to various degrees of
percent NCV reductions for comparable time periods up to 15 compressive forces were performed in the cat. 65 Following 2
minutes for respective age groups. Beyond 15 minutes, re hours of hind limb compression with pressures between 800 and
sponses could generally no longer be observed across this seg 1200 mmHg, weakness of the musculature distal to the com
ment because of profound amplitude reduction, As noted above, pression was noted to persist for several weeks prior to com
however, wrist stimulation continued to reveal a response de plete recovery. This time period was far too short for Wallerian
spite the lack of demonstrable potentials from elbow stimula degeneration to have been the cause of paralysis, Longitudinal
tion, Over the same time frame, the duration of the sensory histologic preparations of the compressed regions demonstrated
nerve action potential incrementally increases for persons that there had been focal or segmental demyelinationlremyeli
30-59 years of age from 3.7% to 101.8% of the preischemic nation located beneath the compressive device only with axonal
value, Younger individuals (10-28 years) demonstrate a larger, sparing, i.e" an absence ofWallerian degeneration. This type of
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 133
~Jv
eral nerve lesions caused by lead intoxication. 115 The documen
tation of segmental demyelination was extremely important day I _ _ _ _...._ _
because it related a specific type of histologic nerve injury (seg
mental demyelination) to physiologic conduction block result
~~
ing in clinical weakness in the absence of Wallerian
degeneration. It also focused attention on a relatively common 3S~
type of reversible weakness: acute demyelinating block.
Continued work in compressive segmental'demyelinating le
~4-
sions has shed considerable light on the underlying anatomic
changes arising from localized pressure that produce action po
tential blockade with the associated characteristic clinical find
ings of weakness and numbness.
100
Figure 4-8. Recovery of various animals IU
Q
after conduction block generated by a tourni ::'.)
quet The muscle action potentials are recorded
from the abductor hallucis muscle with neural stim
ulation at the thigh and at the ankle. The vertical
..
!:
.s
2
c
scale shows the amplitude of the muscle response
IU
to proximal stimulation as a percentage of the re 411
sponse to distal stimulation. The horizontal scale is
in days after tourniquet application. The animal
number and duration of tourniquet application in
...,
Z
0
411
TIME IN DAYS
134 - PART I FUNDAMENTAL PRINCIPLES
resulted in 6 months of recovery time and more Wallerian de of the faster-conducting fibers may have been preferentially
generation than nerves exposed to 1 and 2 hours of compres slowed with conduction block of other fibers. The continued
sion. It can be seen that mild lesions are primarily composed of demonstration of nerve conduction slowing despite resolution
fibers demonstrating conduction block while severe lesions are of conduction blockade strongly suggests that the fastest-con
mixed. A mixed lesion is one in which there is a combination of ducting fibers had regained the ability to sustain an action po
both action potential blockade and Wallerian degeneration. In tential across the damaged segment but at a much reduced
other words, longer times of neural compression can be ex conduction velocity. The process mediating action potential
pected to generate lesions with a spectrum of nerve injury from propagation had obviously been restored but at a less than
simple action potential blockade with full recovery to Wallerian normal level. Unfortunately, the time required to achieve a max
degeneration requiring quite prolonged recovery times. imal conduction velocity was not explored. The maximum ve
Wallerian degeneration was confirmed by the demonstration of locity following compression was not achieved at 6 months and
fibrillation potentials with standard concentric needle explo mayor may not have required more time. Because the ampli
ration in the affected muscles. tude of the response immediately following compression was
In addition to the complete action potential blockade across smaller and conducted appreciably slower, it is likely that a sig
the compressed zone, a number of additional electrophysiologic nificant number of the fast-conducting fibers were blocked. One
findings were noted. 93 The nerve conduction velocity range be can only conclude that a different fiber population may have
neath the tourniquet prior to pressure elevation was 60.4-84.5 been examined with proximal and distal stimulation. As a result,
mls (mean of 70.3 mls) while that distal to the tourniquet was the practice of calculating conduction velocities across regions
58.8-80.0 mls (mean of 68.7 mls). Following inflation of the of conduction block is of questionable merit as one is compar
tourniquet for the above-noted times and subsequent deflation, ing the fastest-conducting fibers below the lesion with slower
the conduction velocity under the tourniquet was initially conducting fibers proximally. The amplitude. however, can be
13.8-44.0 mls (mean of 29.0 m/s) while that in the noncom used to gain a rough approximation of the amount of blocked
pressed segment remained essentially unchanged (56.7-79.0 fibers keeping in mind that severe lesions most likely have re
m/s; mean of 65.8 mls). Nerve conduction velocity assessment sulted in some axonal loss. After about 7-10 days, expressing
when the nerve had been determined to be recovered (absence the proximal amplitude as a percentage of the distal amplitude
of conduction block: 28-180 days) reveals the proximal con should eliminate Wallerian degeneration as a contributing factor
duction velocity range had increased but was still below pre and primarily yield information regarding conduction block.
compression values at 44.3--62.5 mls (mean of 55.1 m/s), while The reason Wallerian degeneration no longer contributes to the
the distal velocity was within acceptable variation of the pre distal potential is because the neuromuscular junctions have dis
compression values, i.e., no change. integrated and these fibers are incapable of contributing to the
Importantly, the conduction velocity through the compressed evoked muscular response to either proximal or distal neural ex
segment of nerve was dramatically slowed and showed an in citation. The same theoretical principles apply to sensory nerves
complete recovery, even though conduction block had been de with the exception that approximately 10 days are required for
termined to be resolved. This suggests that initially there may sensory nerves undergoing Wallerian degeneration to no longer
have been blockade of the fastest-conducting fibers with the be excitable.
slower fibers conducting across the lesion. Additionally, some The morphology of the compound muscle action potential
following compression revealed an interesting change com
pared to the precompression shape (Fig. 4-9). Prior to compres
. i. .__~_
sion. the evoked compound muscle action potential was the
expected biphasic, initially negative waveform. As the potential
recovered from compression, it was no longer a simple biphasic
waveform but appeared with multiple phases. As time pro
gressed and recovery proceeded, the morphology of the wave
form again assumed the anticipated biphasic response. This
finding was explained on the basis of altered conduction veloci
]
ties of the recovering fibers leading to an initial temporal dis
persion. As the fiber population assumed a more normal
distribution, the arrival of action potentials at the muscle
became more synchronous, thus generating a biphasic-appear
ing potential. The onset latency ofthe recovering waveform also
demonstrated a progressive shortening with recovery.
. .......... .... . When nerve action potentials were recorded and compared to
the pure motor response, it was observed that the afferent and ef
msec ferent nerves were affected equally by the compressive forces. 93
Thus, there appears to be no preferential injury to sensory or
Figure 4-9. CHAP conduction delay/temporal dispersion. motor nerves to compression. The demonstration that there is
Evoked muscle action potentials shown from the abductor hallucis mus electrophysiologic blockade of the action potential propagation
cles before (A) and 73 days after (B) tourniquet application at 1,000 across the site of neural compression and slowing of nerve con
mmHg for 180 minutes. Note the prolonged time of conduction and duction velocity within 24 hours of injury is incompatible with
temporal dispersion for the action potential following trauma. (From demyelination being responsible for these findings because the
Fowler TJ. Danta G, Gilliatt RW: Recovery of nerve conduction after a demyelinating process requires several days. The explanation for
pneumatic tourniquet: Observations on the hind-limb of the baboon. J these observations is found in the histologic appearance of
Neurol Neurosurg Psychiatry 1972;35:638-647, with permission.) nerves subjected to the above-noted compressive forces.
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 135
ANATOMIC FINDINGS
In the animal model of neural compression in baboons, longi
tudinal histologic sections were performed on the injured nerves
with both light and electron microscopy.217.218,219,221 The blood
pressure cuff covered an expanse of nerve approximating 5.5
cm and histologic examination was carried out just distal,
across, and immediately proximal to this segment of nerve.
-1t....-
= .;"p
CuII
:c
Careful examination of single teased nerve fibers were per -~
formed within the first several days to several weeks following
compression. Only large myelinated fibers were affected and
demonstrated a unique lesion not previously observed.
Figure 4- 1,. Region of neural intussusception occurring only
Specifically, a mild form of anatomic distortion occurred where
at the edges of the pneumatic tourniquet.Arrows indicate di
there was invagination of one paranodal region into the adjacent
rection of invagination of adjacent paranodes. (From Ochoa J. Fowler
paranodal segment (Fig. 4-10). The extent of this invagination
TJ, Gilliatt RW:Anatomical changes in peripheral nerves compressed
by a pneumatic tourniquet.J Anat 1972; I 13:433-455, with permission.)
paranode into the next .. The invagination process is noted at both entire internodal segments are demyelinated but more com
edges of the tourniquet with the invagination pointing away monly it is only the affected portion of the internodal myelin
from both edges (Fig. 4-11). The actual node of Ranvier is thus that is removed. In the lesion produced by compression main
buried beneath the paranodal myelin of the furthest of the two tained for periods of 3 hours, Wallerian degeneration between
paranodes from the pressure gradient. In order for the paranodal 0-30% was noted in some of the fibers that corresponded to the
myelin to invaginate into the adjacent node, it must be elongated electrophysiologic findings of reduced compound muscle action
as if one were to roll up a single sheet of newspaper and pull on potentials below the lesion site compared with the precompres
the inner most portion to extend it from the inside outward. This sion amplitude. 93
stretching of myelin disrupts its attachment to the axon at the The process of remyelination repairs the altered portions of
paranodalloop region. The paranodal myelin being invaginated the internodal regions. The Schwann cells apparently undergo
buckles and envelops the invaginating segment. Interestingly, mitosis and remyelinate the newly demyelinated segments, gen
the Schwann cells do not dislocate but maintain their original erating intercalated thinly myelinated segments (Fig. 4-12). It is
positions. It appears that the Schwann cells are more firmly an anticipated that these segments eventually regain the preinjury
chored to the surrounding basal lamina and investing connect myelin thickness although extended observations were not per
ing tissue. This combination of inner myelin sheath sJippage formed. Of interest is the observation in some of the compressed
and stable Schwann cell positioning creates the appearance of nerves that remyelination had not occurred 3 months after injury.
nodes of Ranvier at the sites of the compressive insults. These There was a subpopulation of fibers following compression with
areas are referred to as "pseudonodes," because there is an en evidence of intramyelin and peri axonal edema, giving the ap
compassing myelin sheath as opposed to bare axons at true pearance of a grossly swollen myelin sheath separated from but
nodes of Ranvier (Fig. 4-10), surrounding a shrunken axon (Fig. 4-13). It appears that these
Within 7-14 days of the compression, there is paranodal de swollen nerve segments are eventually invaded by macrophages,
myelination of both the stretched and invaginated myelin seg which dispose of the edematous material and restore the nerve
ments (Fig. 4-12). By 15 days, there is usually a complete absence segment to a functional level. This prolonged neural dysfunction
of invagination with only demyelination noted. Occasionally, the is proposed to be the etiology of the conduction block, which
lasts for 3-4 months when one would have anticipated neural
repair and functional conduction as opposed to continued action
potential blockade.217.218 The lesion produced beneath the edges
of the pneumatic tourniquet should be viewed as a series of indi
vidual paranodal regions, each with its own potential for a vari
able recovery time. As a result, the affected nerve cannot become
physiologically functional until all of the paranodal regions have
been repaired. One or two "delayed recovery" nodes are all that
is necessary to render this particular nerve nonfunctional. In
short, with respect to remyelination a weak link analogy can be
postulated in that " .. , a remyeUnated fiber is only as functional
as its most severely affected internode."112
An important finding of the myelin intussusception phenom
enon is that it occurs only in relatively large myelinated fibers,
diameters greater than 5 pm, with sparing of the smaller myeli
nated fibers. This is significant because it explains the finding
of absent motor function and some sensation, but the preserva
tion of pain and temperature modalities, i.e., those sensibilities
mediated by the small myelinated fibers. It is postulated that
considerably more force is required to displace the contents of
small axons compared to larger ones. Additionally, there is min
imal, if any, narrowing in the smaller axons in the paranodal
region. The smaller axons would most likely become crushed
prior to demonstrating the above invaginations so characteristi
cally noted in the larger myelinated fibers.
Using a small nylon cord to apply a compressive force about
a restricted portion of nerve in subhuman primates revealed
findings similar to those of the tourniquet but that were much
Figure 4- I 2. A series of single teased nerve fibers. A. Normal more localized.260 Additionally, there was a direct correlation to
nodal and paranodal region of a single nerve fiber. B, Mild degree of in anatomic injury, clinical findings, and electrophysiologic results
vagination of one paranodal segment into an adjacent one. C-D, to the severity of pressure per unit area. This model of anatomic
Progressively more severe intussusception compared to B.There is thin disruption of the paranodal myelin is postulated to be the mech
ning of the myelin sheath in D. E, Demyelination of the affected paean anism responsible for the paralysis and sensory findings noted
odal region. F,An example of early remyellnation with the formation of a in human pressure palsies, such as "Saturday night palsy." It is
so-called intercalated segment involving only a portion of the internodal rather difficult to prove this point in humans as one would have
region that was invaginated. (From Ochoa J, Fowler TJ, Gilliat RW: to expeditiously investigate histologically known individuals
Changes produced by a pneumatic tourniquet. In Desmedt JE (ed): New with acute pressure palSies who had coincidentally expired.
Developments in Electromyography and Clinical Neurophysiology,Vol.2. One may well ask if nerve fibers subjected to segmental
Basel, Karger, 1973,pp 17+-ISO,with permission.) demyelination without loss ofaxons demonstrate fibrillation
Chapter 4 PERIPHERAL NERVOUS SYSTEM'~ REACTION TO INJURY - 137
The Schwann cell extends for approximately 1.0 mm over the channel distribution along the various portions of the axolemma
longitudinal extent of the axon and reaches this length because is found in immunocytochemical, saxitoxin-binding, and volt
of peripheral nervous system growth elongating its original 300 age clamp methods.25.55.85.2 I 2.252.253 All of these studies strongly
/Jm length in the immature animal. 172 •295 By wrapping itself suggest that sodium channels are primarily localized in high
around the axon multiple times, a substantial thickness of density at the nodal membrane and at significantly lower den
myelin layering results. Adjacent Schwann cells with their ac sity in the internodal membrane (Fig. 4-14). Therefore, voltage
companying myelin sheath approach each other within about sensitive sodium channels are concentrated at the nodes of
1.0 /Jm or less. '9 As noted previously, this 1.0 /Jffi region of Ranvier and in very low concentrations along the internode.
axonal membrane devoid of myelin is referred to as the node of The issue of potassium channel localization is both interest
Ranvier. ing and important to understand, particularly with respect to
The axonal membrane, therefore, is enveloped by a discon mammalian as opposed to squid nerves. The use of voltage
tinuous myelin covering except at approximately I-mm inter clamps at the nodes of Ranvier demonstrates that there are very
vals where it is exposed to the extracellular environment. few if any voltage-gated potassium channels. 34.54 Two pharma
Multiple different experimental techniques have detailed the cologic agents, 4-aminopyridine (4-AP) and tetraethylammo
molecular structure of the axolemma with respect to ion gates nium (TEA), are known to specifically block rapidly activating
present along various aspects of the axon, both beneath the or "fast" potassium channels and delayed rectifying or "slow"
myelin sheaths as well as the exposed nodes of Ranvier. Various potassium channels, respectively.306 A combination of these
cytochemical investigations have demonstrated that there is a blocking agents and intra-axonal recordings of eNS myelinated
distinct difference between the axolemma of the internode (por nerve reveal that repolarization of the action potential in these
tion surrounded by myelin) compared to that of the node of fibers is not dependent upon TEA-sensitive potassium channels
Ranvier.238 The nodal membrane is found to have very similar nor is the action potential morphology altered by blocking the
characteristics to that of the initial segment of the axon (axon 4-AP-sensitive potassium channels. II7,I73.174.304 Unlike the famil
hillock) just distal to the cell body, Le., high sodium channel iar squid nerve, mammalian nerve does not depend upon potas
density.7° Also, freeze-fracture studies of the axonal membrane sium channels for repolarization but instead re-establishes the
demonstrate that the external surface of the nodal membrane resting membrane potential through sodium inactivation and
contains membranous proteins with a density approximating sodium "back-leak" currents. 34•S4
1300l/Jffi2.183.2S8 The same technique, however, reveals that the The fast 4-AP-sensitive potassium channels appear to be
internodallparanodal membrane contains a significantly re preferentially located in the paranodal and internodal axon
duced particle density of 100-2oo//Jffi2. There is a suggestion membrane, i.e., beneath the myelin sheath (Fig. 4- I 4). Although
that the physically observed particles in freeze-fracture tech the exact function performed by these fast potassium channels
niques correspond to the previously noted collections of sodium is unknown, it is postulated that they serve to stabilize the
channels in this same region. Of course, it is possible that the axonal membrane following an action potential to prevent repet
observed particles may represent a subset of sodium channels or itive firing to a single stimulus.176.254 It is also possible that there
multiple sodium channels per detected particle. Of interest is is a role for these potassium channels to help generate the rest
that nonmyelinated fibers demonstrate the above-noted particles ing membrane potential.56
contained in the external membrane surface at a density of The slow TEA-sensitive potassium channels are present in
150-3OO//Jffi2.24 Further support for the heterogeneity of sodium the axonal membrane in some mammalian myelinated fibers
(Fig. 4_14}.I3·178.179Jt appears that the slow potassium channels
are preferentially activated in prolonged depolarizations such as
those arising from high-frequency stimulation or discharge.
There is a suggestion that in repetitive firing of the axon, the
-_ .....
ON. 0Kf
slow potassium channels help to modulate the ability of the
axonal membrane to participate in successful action potential
regeneration. This is accomplished by the generation of an after
--- ----_ ...... _---- - --_ _----
---P-----' -----
OKs OrR
.... hyperpolarization that decreases the generation of an undesired
burst of action potentials resulting from the initially generated
potential, thereby resulting in a coordinated as opposed to unco
ordinated firing pattern. The actual location of these slow chan
nels is in question, but they appear to be located in both the
Figure 4-14. Hodel of proposed ion channel organization in nodal and internodal axon membrane.
myelinated mammalian nerve fibers. The sodium channels are A fourth intramembranous ion channel is believed to be pre
present in high concentration in the axonal membrane at the node of sent in mammalian myelinated nerves and referred to as an
Ranvier but are in very low density (less than necessary for action po inward rectifier channel (Fig. 4-14).13.86 Hyperpolarization of
tential propagation) in the internodal region. Potassium channels (4 the axon membrane is the stimulus that activates this channel to
AP-sensitive) are distributed in a complementary fashion to the allow an inward current into the axon. This inward current
sodium channels, i.e., abundant in the internodal region (covered by serves to prevent excessive hyperpolarization, thus regulating
myelin) but less so at the node of Ranvier. gNa, sodium channels; gKf, the excitability of the membrane, i.e., helps keep the membrane
fast (4-AP-sensitive) potassium channels; gKs, slow (TEA-sensitive) from deviating too far from the resting membrane potential and
potassium channels; giR. inward rectifier channels. (From Waxman SG: threshold level. Excessive hyperpolarization tends to prevent re
Molecular organization and pathophysiology ofaxons. In Asbury AK, current action potential propagation, particularly at intervals
McKhann GM. McDonald WI (eds): Diseases of the Nervous System: overlapping the hyperpolarized time frame. There is a sugges
Clinical Neurobiology. Philadelphia, WB. Saunders. 1992, pp 25-46. tion that both sodium and potassium ions may be permeable to
with permission.) these channels.
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 119
Electrical Aspects B
Extracellular recordings along the surface of single motor ...Ai '__
nerve fibers during action potential propagation reveal a number
of interesting findings (Fig. 4-15). Moving a recording electrode
../ \.
....f\",...,
pair across the myelinated internodal region demonstrates an ~
external longitudinal current with essentially a constant latency $""""-"
but slightly declining amplitude. At discrete intervals there is a -./"
noticeable shift in latency for the externally recorded current, ....r-;.
Figure 4-16. Equivalent circuit diagram for a nerve fiber. Axon with investing myelin sheath shown forming two nodes of Ranvier (A and
B) and an internodes segment. The equivalent circuit diagram representing the combined resistive and capacitive components of the various as
pects of the nerve fiber. Note that each node of Ranvier can be thought of as consisting of a variable resistor (~; changes with voltage level, i.e.,
sodium activation) and capacitor (CN).The internodal region of the nerve also consists of a membrane resistance (~) and membrane capacitance
(C M). The internal resistance of the axoplasm is represented by RA• The inward-directed current at node A is shown to have a rapid rise time and
relatively large amplitude.This same current is reduced in amplitude and rise time by the time it reaches node B because of having lost some of its
content through the membrane resistance and capacitance as well as axoplasm resistance. If the current at node B is of sufficient magnitude to
reach threshold, an inwardly directed current generated at node B similar to that depicted for node A will be produced to subsequently activate
the next node in line. (Modified from Rasminsky M: Pathophysiology of demyelination. In Didactic Program,AAEM, 1980. Rochester, MN,AAEM,
1980, pp 29-34.)
threshold> 1.0. Should this value fall below unity, one can an recovers to the predisease state provided the induced lesion was
ticipate failure of action potential propagation. not too severe. One of the earliest electrical abnormalities noted
in the above neural insults was slowing of nerve conduction
Anatomic/Electrical Aspects of Demyelination through the demyelinated segments.58.202.203 There was an overall
There are a number of ways to produce experimental segmental reduction in the maximum recorded conduction velocity from
demyelination of varying degrees. One method of accomplishing 94.8 mfs to 33.7 mfS.202 Also, there was a greater proportion of
focal or paranodal demyelination has already been described in fibers conducting at the slower conduction velocity than prior to
detail, i.e., compression of varying degrees arising from pneumatic the nerve insult. This suggested that there was significant slow
toumiquets or nylon bands. 218 Investigators have also used two ad ing of conduction in the fastest-conducting fibers down to the
ditional methods to induce focal demyelinating lesions with rela lower value. The slowing of conduction is not believed to result
tive axonal sparing. The first concerns induction of experimental in weakness but may account for loss of deep tendon reflexes
allergic neuritis in animals. Lesions occur in the peripheral nerve, where the synchronous arrival of impulses is important to elicit
spinal ganglia, and nerve roots as focal perivascular accumulations a response. 105,280 As previously noted, normal internodal con
of inflammatory cellS.58,135.160,185 These regions of inflammatory cel duction time is approximately 20 IlS. 278 In demyelinated nerves,
lular aggregates are associated with the focal breakdown of however, internodal conduction time can reach 500-600 IlS. If a
myelin. The other method of generating focal demyelinating le nerve were previously conducting at 60 mfs over a distance of
sions in the peripheral nervous system is through the application 200 mm, the internodal conduction time would be ] 6.7 IlS. For
of diphtheria toxin-antitoxin mixtures.201.202,309 This type of inocu this nerve, an increase in the internodal conduction time to 500
lation with 0.5-2.0 ml of the mixture results in weakness onset in IlS would result in a dramatic reduction in conduction velocity
5-10 days following injection with a continuation of symptoms to 2.0 mfs. Although most nerves continue to conduct in a salta
for an additional 5-20 days with subsequent recovery, and occa tory fashion prior to block,246 there is evidence that in a least
sional death of the animal receiving higher dosages. An additional some nerve fibers conduction may actually become continuous
method used to "dissolve" sequential layers of myelin has also across the demyelinated segment similar to normal unmyeli
been performed by using saponin, a fat solvent, on amphibian nated neural conduction. 28 In addition to action potential propa
nerves. 284 Although this is obviously not a naturally occurring dis gation slowing and blockade, there are a number of additional
ease, the method is nevertheless useful for examining conduction electrical abnormalities occurring over demyelinated segments
through controlled demyelinated regions of nerve. The end result of nerve. Close inspection of the waveform morphology of
of the above processes is an initial thinning of the internodal action potentials conducting across a demyelinated region re
myelin, usually, though not exclusively, beginning about the Para veals that there is usually a reduction in amplitude and an in
nodal region and extending varying distances along the internode. crease in the potential's duration, thus producing temporal
The myelin sheath becomes significantly thinner and may disap dispersion. The nonuniform slowing of multiple fibers results in
pear completely. Once the diseased myelin is removed through a less than synchronous arrival of action potentials at the record
phagocytosis or Schwann cell ingestion, a new myelin layer is ing site compared to the previous unaffected temporal separa
formed. As noted previously, this newly formed myelin sheath is tion of action potentials. A less synchronous arrival of
typically thinner than the original sheath and may take quite some individual action potentials disturbs the usual summation of
time, if ever, to reach the thickness of the unaffected internodal electrical impulses resulting in a smaller, polyphasic, and in
myelin sheaths. creased duration waveform.
The clinical consequences of the above-noted lesions are es Internodal conduction times in excess of 500-600 flS essen
sentially similar in that they result in weakness, which eventually tially result in failure of conduction, i.e., conduction block. 246 It
Chapter" PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 141
is the failure of action potential transmission (conduction block) to an elevation in temperature, lowering the temperature by as
that results in the observation of clinical weakness. As one little as O.5°C decreases the internodal conduction time suffi
might anticipate, if the action potential does not reach the motor ciently to ensure action potential propagation. It has been deter
nerve terminal, the muscle membrane cannot be depolarized mined that an increase in temperature results in a decrease in
and there is a lack of muscle activation with ensuing weakness. the action potential rise time, suggesting a more rapid initial in
Conduction block can be frequency-related, whereby low-fre crease in the inwardly directed sodium current.94.228.247 This
quency stimuli continue to conduct without difficulty, in con rapid rise time and quicker establishment of optimal sodium
trast to a high-frequency train of stimuli that may result in current flow decreases the internodal conduction time, thereby
action potential blockade.64 •161 ,307 This is a direct reflection of an increasing conduction velocity in normal fibers. There is also
increase in the refractory period of demyelinated nerve. 203.246.273 less time for the current to flow as well as sodium channel inac
Recall that there are few sodium channels beneath the intern tivation occurring sooner, which shuts down sodium influx and
odal membrane. Removal of the myelin sheath requires the decreases the action potential's total duration.146.153.283 This is
action potential to conduct across a segment of nerve with a compatible with action potential propagation in normal nerve
sodium channel density that is most likely too low to sustain because the safety factor is 5-7 times that absolutely needed to
action potential propagation. A small amount of demyelination ensure neural propagation. In demyelinated nerve, however,
may only serve to slow the internodal conduction time by pro current is lost through the demyelinated internodal region as
longing the time to reach threshold, but if enough of the inex well as the other factors tending to suppress conduction, result
citable membrane is exposed, action potential failure most ing in a reduced tolerance for less current flow and the rapid
likely occurs. Additionally, exposure of the potassium channels sodium inactivation (see above). The end result of temperature
in the internodal region will attempt to hold the membrane po elevation in a demyelinated nerve with a reduced safety factor
tential close to the potassium equilibrium potential, thus resist and more time required to reach threshold is less current flow
ing a move of the membrane potential toward the sodium ing for a shorter period of time compared to a lower temperature
equilibrium potential, i.e., suppressing any attempt at depolar resulting in action potential propagation failure, i.e., conduction
ization. 3m There may also be a "pump-mediated" hyperpolariza block. This is the most likely cause for the phenomena of in
tion following an action potential, which also results in a creased weakness of patients with multiple sclerosis when sub
reduction in the safety factor of transmission. 31 Recall that fol jected to an elevation in body temperature, i.e., the "hot bath
lowing an action potential, the influx of sodium acts to maxi test."124 A reduction in temperature restores action potential
mize the exchange of sodium for potassium thus leading to a propagation because sodium inactivation is slowed permitting
slight hyperpolarization in that the sodium-potassium pump current to flow for a longer period of time, thus generating suffi
overcompensates to a small degree (see Chapter 1). This hyper cient transmembrane voltage alterations to induce sodium gate
polarization is relatively short-lived, with the resting membrane activation at the next node of Ranvier.
potential eventually settling back to its steady-state level. Additional electrical abnormalities can be detected in de
There is a further relationship between this "pump" effect and myelinated nerves. Spontaneous generation of impulses have
rate-dependent conduction block of action potential transmis been observed to arise in chronically demyelinated cat dorsal
sion. 161 Most normal nerves can conduct trains of impulses at column axons. 274 There is also the phenomena of epbaptic con
rates of 50 Hz or more for time periods approaching several duction or "cross-talk" between neighboring nerves with less
hours. Following the generation of multiple action potentials, than an optimal complement of a myelin sheath. Ephaptic con
the amount of intra-axonal sodium accumulates faster than can duction is a process where impulses interact with adjacent
be removed by the sodium-potasium ATPase pump mechanism. nerves thereby setting up abnormal impulses in them, leading to
It is believed that this sodium accumulation is even greater in various sensory or motor disturbances.175.297 This finding has
demyelinated nerve still capable of mediating neural conduc been described in both acutely and chronically damaged nerves.
tion. This is because of a greater surface area of internodal The two most common occurrences of ephaptic conduction
membrane exposure and current flow. The increased intracellu were noted in nerve fibers ending in neuromas and nerve roots
lar concentration of sodium in tum stimulates the electrogenic of dystrophic mice. 177.249 There is also some evidence that de
sodium-potassium pump, thereby hyperpolarizing the mem myelination can lead to an increase in mechanosensitivity of
brane and increasing the voltage differential between the new certain nerve fibers and may account for the so-called
resting membrane potential and the threshold level,31 As a result Lhermitte's sign, paresthesias in radiculopathies, straight leg
of more current required to reach threshold because of the and arm raising signs, and other similar observations.152.303
greater voltage difference, the neural safety factor is reduced,
which then results in conduction block, i.e., a rate-dependent Computer Modeling of Myelin Loss
conduction block. Various computer models have been developed to better un
A number of interesting findings have been noted with re derstand the consequences of myelin loss on action potential
spect to varying the temperature and observing the conse propagation.180.208.301 A number of known parameters regarding
quences of this action on neural conduction velocity and myelinated nerves and action potential propagation characteris
blockade in demyelinated nerves.63.247.265 Generally, increasing tics were programmed to simulate normal action potential prop
temperature within the normal physiologic range for normal agation. Because normal neural conduction is easy to measure
nerve results in an increase in conduction velocity. In normal and quantify, it is rather simple to verify if the computer model
mammalian nerve fibers the internodal conduction time at 30°C provides accurate results when compared to reality. After
is approximately 30 J.Is, while at 37°C, it is about 20 J.Is. In de having ensured that the program is capable of predicting the an
myelinated internodes, however, the internodal conduction time ticipated results under normal conditions, the program can be
at 35°C approaches 360 J.IS. Any further increases in tempera altered with respect to various anatomic aspects of the nerve to
ture result in action potential conduction block. Once conduc simulate different disease conditions and assess whether simu
tion block is produced in some demyelinated fibers secondary lations match clinically observed results. It is then possible to
142 - PART 1 FUNDAMENTAL PRINCIPLES
change one variable at a time to investigate how these alter sodium ions mediating the current flow to "cross the nodal
ations produce the clinically recorded response. This technique membrane" through a net transfer of charge. The intracellular
has been specifically applied to learn more about action poten sodium ions "neutralize" some of the intracellular anions' at
tial failure in conditions resulting in loss of myelin, i.e., seg traction for the extracellular ions, thus allowing these ions to
mental demyelination from various diseases like compression move away from the outside of the axolemma and generating a
neuropathies and multiple sclerosis. current transfer across the membrane. This current pass~ge
Initially, a myelinated nerve is simulated where an action po across the node results in altering the transmembrane voltage. If
tential conducts with the expected characteristics of normal the voltage change is sufficient, threshold is achieved and an
neural propagation. For simplicity, an entire internodal portion action potential is generated through sodium activation of the
of myelin is then removed without altering the axon's conduct voltage-dependent sodium gates in the nodal membrane. This
ing properties. Specifically, the entire aspect of the denuded newly formed inward-directed current then repeats the process
axon is assumed to possess a sodium channel density equal to of nodal depolarization at the next node of Ranvier, producing
that of the node of Ranvier. We now know that this is incorrect the expected saltatory conduction.
but at the time of the study, this information was not available Once the internodal myelin is removed, a separate set of cir
and the investigators assumed that the internodal axolemma was cumstances now becomes operative to adversely affect action
similar to the nodal region, i.e., excitable. The action potential potential propagation. Thinning or complete removal of the
fails to conduct across the demyelinated segment to excite the myelin component does not alter the intra-axonal resistance to
nodes distal to the region of demyelination, i.e., conduction current flow or the amount of current generated at the node of
block occurs. The finding of action potential failure despite an Ranvier compared to the normal situation. There is, however, a
internodal density of sodium channels equivalent to the nodal profound effect on the internodal resistance and capacitance.
region is rather interesting and implies that even with a rela Myelin removal now permits the internodal intra-axonal current
tively high sodium channel density, neural propagation could to pass relatively unrestricted through any passive sodium chan
not cross the demyelinated region. In other words, conduction nels present in the axolemma, i.e., the membrane resistance
did not become continuous as in unmyelinated nerve despite a component is significantly lowered compared to normal. A
high sodium channel availability. The explanation for this ob greater portion of the intra-axonal current compared to normal,
servation is rather interesting and provides significant insight therefore, is dissipated through the resistive component of the
into the requirements for saltatory action potential propagation membrane. Also, the entire internodal membrane can now act as
in myelinated fibers. In order to appreciate the implications of a large set of capacitor plates and accumulate significant
this finding of action potential blockade, we must return to the amounts of extracellular ions. As the intra-axonal current now
previously discussed "electrical circuit" representation of the travels beneath the exposed internodal axolemma, a large
myelinated axon. amount of current can cross the membrane in the capacitive cur
As previously noted, depolarization of a node of Ranvier ex rent transfer. The decreased resistive and increased capacitive
cites the adjacent node by inducing an inward-directed current, aspects of the internodal membrane result in a large current loss
which travels intra-axonally toward the next node. The current across the entire internodal region. As a result, there is little cur
flow experiences a minimal loss over the internodal region rent available to generate a transmembrane voltage shift of suf
through both the capacitive and resistive components of the in ficient magnitude to activate the voltage-dependent sodium
ternodal membrane. Recall that because of the insulation prop channels at the node of Ranvier because of the diffuse loss of
erties of the internodal myelin, the capacitance is low and the current. Even if the internodal membrane had a high density of
resistance is high. In other words, there is minimal ability of the sodium channels similar to the nodal membrane (see above
intra-axonal current to escape across the axolemma and invest computer example), conduction continues to fail because there
ing myelin sheath. A finite amount of current is also dissipated is insufficient current to depolarize any aspect of the membrane.
within the axon over the internodal region because of the intra The decreased resistance and increased capacitance of the in
axonal resistance of the axoplasm. Despite the three avenues of ternodal membrane depletes the available current to such an
current loss noted, there is still 5-7 times the amount of current extent that the normal 5-7 times current safety factor is reduced
required to effect depolarization at the next available node of below 1, i.e., an insufficient amount of current is available at
Ranvier. any single region of membrane to generate an action potential.
At the nodal region, the bare axolemma allows the remaining According to computer models, 97.3% of the myelin can be re
intra-axonal current to cross the nodal membrane through its re moved and action potentials still propagate across the internodal
sistive and capacitive components. Remember that the small region. Once the myelin thickness is reduced to 2.5% of its
region ofaxolemma at the exposed membrane has some passive normal thickness, there is too much current lost across the in
sodium channels and therefore a lower resistance than the in ternodal region and the safety factor becomes unfavorable for
ternodal region, thus allowing current to cross the membrane. action potential propagation resulting in conduction block.
Additionally, the absence of myelin at the node creates a large Introducing a short internodal region of 400 IJ1l1just proximal
capacitance because it allows the extracellular sodium ions to to the demyelinated segment does not alter the above situation
accumulate about the node secondary to the intracellular attrac and there is continued conduction failure. Placing two-200 11m
tion of negative ions. The thin axolemma separating the intra internodes in the same location noted above, however, results in
cellular and extracellular fluid permits the intracellular anions the action potential propagation into and across the demyeli
to exert a larger attractive force on the extracellular positive ions nated segment. The two interesting observations in this instance
compared to the increased distance between the intra/extracellu are (1) action potential propagation across the demyelinated
lar regions across the internode. The nodal membrane behaves segment in a continuous manner similar to that in unmyelinated
as two capacitor plates with significant charges permitted to nerves, and (2) repair of conduction block. The same simulation
build up on either side, i.e., a capacitor with a high capacitance is repeated for an internodal axolemma with a significantly re
value. As a result, it is relatively easy for the intracellular duced sodium channel density. The same results of action potential
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 143
conduction across the unmyelinated segment with repair of con there is less current available at the node and it must flow for a
duction block are observed. Adding two short internodal regions longer period of time to reach threshold. The increase in time is
just proximal to the demyelinated segment results in action po reflected as a decrease in the internodal conduction velocity,
tential conduction by increasing the amount of current available thus producing a slowing of neural conduction. This is clearly
for this region, i.e., the safety factor is increased. This increase shown to be the case when conduction times approaching 600
is accomplished by the location of the two internodes. These JIS have been documented in demyelinating diseases (see
two internodal regions are simultaneously activated by the prox above). The same ideas of resistive and capacitive current loss
imal node of Ranvier. As a result of two current generators can be applied to the temperature effects with respect to con
being coincidentally activated at the same time, a large amount duction block. Increasing neural temperature reduces the safety
of current is injected into the membrane. This large influx of factor by facilitating early sodium inactivation. Less current
current is of a sufficient magnitude to tolerate a significant loss availability may result in conduction block across a partially de
across the demyelinated membrane through the resistive and ca myelinated segment because the amount of current at relatively
pacitive current loss mechanisms with enough current left over lower temperatures is just sufficient to exceed capacitive/resis
to achieve the voltage-dependent sodium channels' threshold tive internodal current loss but is insufficient at the higher tem
level at the next normal node of Ranvier/internode region. The perature. Reducing the temperature again restores neural
increased amount of current secondary to the two activated conduction as current is permitted to flow for a longer time
nodes, elevated safety factor, is now capable of repairing the period to overcome the capacitive/resistive current loss, thus
previously noted conduction block. The observation of short in reaching threshold and action potential generation.
ternodes interposed prior to a demyelinated segments has not Of course, the above computer simulations demonstrate
been clinically documented but certainly poses a method to clearly the importance of remyelination. Establishing a new in
repair conduction block. ternodal myelin thickness at least 2.7% of the original sheath
The concept of action potential failure secondary to myelin loss thickness reduces the internodal membrane capacitance and in
is referred to as impedance mismatch. An imbalance in the opti creases this region's transverse resistance sufficiently to prevent
mal impedance or various combinations of capacitances and resis enough current leakage to once again reach a safety factor com
tances with respect to current flow no longer produces an optimal patible with action potential propagation. Although the conduc
set of circumstances regarding the electrical properties of the tion velocity may be significantly slowed over this internodal
nerve favoring action potential propagation. Adding short intern region, at least conduction block has been repaired. The re
odes to supplement the amount of current available to overcome myelination is also of significance because it again isolates the
the impedance mismatch is one way of repairing action potential paranodal potassium channels from the extracellular compart
propagation. Removal of myelin from an entire internodal seg ment, thus decreasing any current loss through this mechanism
ment has been modeled on computers but there is reason to be to increase the amount of intra-axonal current available for de
lieve that more limited paranodaI demyelination can also result in polarization of the next node of Ranvier. The mechanism of
an insufficient amount of current available for action potential potassium channel blockade with 4-aminopyridine and TEA has
propagation secondary impedance mismatch. There are examples been tried experimentally to restore action potential propagation
of normally occurring regions of impedance mismatch in the pe with some success in animals. 29•3O The combination of limited
ripheral nervous system where action potential conduction can be clinical success and potentially serious side effects have de
somewhat tenuous, particularly under pathologic condi creased the initial excitement for the potential of 4-aminopyri
tions.300.302.305 The "initial segment" of the anterior horn cell is a dine to be clinically usefuI. 162,268.277 As previously noted, the
region where the nerve becomes somewhat larger and is unmyeli ability of demyelinated peripheral nerves to mediate impulses is
nated compared to its immediately adjacent distal thinner and in part dependent upon a hyperpolarization resulting from the
myelinated portion. At this transition zone the current is spread sodium-potassium pump mechanism and this has been observed
rather thin over the larger region of unmyelinated membrane, thus in the CNS.II7·223 Inhibition, at least in part, of this pnmp by the
allowing more current to escape and lower the safety factor. cardiac glycoside digitalis may be of benefit in decreasing the
Fortunately, there is believed to be an increased number of volt voltage differential between the hyperpolarized membrane po
age-dependent sodium gates most likely capable of generating a tential and the threshold level. Indeed, the administration of this
greater current flow to offset what is lost through the membrane's drug has been shown to be of benefit in both experimental ani
larger surface area. Branch points of peripheral nerves, which usu mals with demyelination and a limited number of patients suf
ally occur at the nodes of Ranvier, are also regions where there is fering from multiple sderosis.163.164.16S Additional experimental
more exposed axolemma permitting a potential for impedance insights from the above computer simulations will hopefully
mismatch. Increased neurogenic jitter and neurogenic blocking continue to bring new and exciting treatment options for pa
may be a result of action potential failure at these branch points in tients affected by various demyelinating diseases.
the collateral tree of terminal axon branch points in reinnervation
secondary to immature and poorly myelinated nerve. A third p0 CLINICAL CORRELATION
tential region of impedance mismatch is the terminal segment of
the motor nerve where there is a transition between the myelinated 1be identification of conduction block is an important aspect
and unmyelinated segment about the neuromuscular junction. of the electrodiagnostic medicine evaluation. This is because
The conduction velocity across the demyelinated segment is some inciting incident has produced a temporary and potentially
noted to be markedly reduced compared to the unaffected seg reversible blockade of neural conduction. Removal of the offend
ments. As previously noted, when the internodal myelin is re ing agent andlor protection of the injured nerve should restore
duced there is a loss of current across this region. If there is a complete neurophysiologic function to the affected structures in
degree of myelin loss capable of reducing the current somewhat nervated. 1be recognition of conduction block implies the patient
but less than the amount capable of totally eliminating the has a relatively good prognosis for recovery. On the other hand,
safety factor, a delay in conduction can be expected. Essentially, failure to remove an anatomic cause of conduction block such as
144 - PART 1 FUNDAMENTAL PRINCIPLES
a compressive ligamentous structure or repetitive motion can there were no root tension signs in the left or right upper limbs.
result in the transition of conduction block into Wallerian degen Sensation, reflex, and muscle testing in the lower limbs were
eration associated with a comparatively less optimal functional normal.
outcome. Conduction block has been considered to represent a Nerve Conduction Studies. Nerve conduction studies are
possible transition between a normal nerve and one that has been performed in the upper extremities bilaterally. The mid-palm
injured and may progress onto more profound damage such as temperature is 33SC on the right and 32.9°C on the left. .
Wallerian degeneration if some type of therapeutic intervention is
DSL S Amp DML M Amp NCV
not performed. I 12 Although this may be the case in a number of
Nerve (ms) (I1V) (ms) (mV) (m/s)
situations, it is also possible for conduction block to persist for
quite some time. As has been previously discussed, animal Right median 3.3 60.0 3.4 10.0 59.0
models of conduction block have persisted for months. 93 Right ulnar 3.2 45.0 3.1 9.0 64.0
Additionally, there are reports in humans of conduction block Right ulnar 8.5 (BE)" 66.0'
persisting from several months to as much as 4.8 years. 138•206.291 8.0 (AE)'
One method of recognizing and localizing conduction block Right ulnar CMAP (AE) duration: 6.2 ms
is to observe a marked reduction in compound muscle action Right ulnar CMAP (BE) duration: 6.0 ms
potential amplitude across a particular portion of nerve, particu Right ulnar CMAP (AE) area: 27.3 m V-ms
larly at known sites of entrapment such as the carpal or cubital Right ulnar CMAP (BE) area: 28.0 mV-ms
tunnels. For example, excitation of the ulnar nerve several cen Left median 3.1 55.0 3.2 9.5 61.0
timeters proximal and distal to the medial epicondyle may yield Left ulnar 3.4 35.0 3.3 6.5 58.0
a CMAP amplitude of 3.0 mV and 7.0 mY, respectively. This Left ulnar 6.3 (BE)' 40.0'
marked drop in amplitude suggests that there is conduction 4.0 (AE)*
block of the ulnar nerve's motor fibers in or about the ulnar Left ulnar CMAP (AE) duration: 6.0 ms
groove. Unfortunately, the correct identification of true conduc Left ulnar CMAP (BE) duration: 5.8 ms
tion block is much more complex than simply comparing Left ulnar CMAP (AE) area: 16.0 mV-ms
CMAP magnitudes. Two hypothetical cases are presented to Left ulnar CMAP (BE) area: 22.3 mV-ms
help clarify the categorization of conduction block and situa
DSL, distal sensory latency; S Amp, sensory amplitude; DML,
tions that may lead to an erroneous diagnosis of conduction
distal motor latency; M Amp, motor amplitude; NCV, nerve con
block. An ulnar nerve compromise is illustrated as this nerve is
duction velocity; ms, milliseconds; !lV, microvolts; mY, milli
frequently involved in neural compression and is a cause of fre
volts; mis, meter/second. Motor and sensory amplitudes are
quent referrals for an electrodiagnostic medicine consultation.
measured baseline-to-peak. Sensory latencies are measured to
ILLUSTRATIVE CASES peak while motor latencies are measured to initial negative onset.
Case #1 • Amplitudes and velocities across fully flexed elbow. AE,
above elbow; BE, below elbow.
History. A 22-year-old female competitive ice skater sus
tained a fall onto the ice while skating secondary to a stress fail Needle Electromyography. A needle electromyographic in
ure of one of her skate's blades. Due to the unexpected nature of vestigation was performed on the left upper limb using a dispos
the equipment failure she was unable to prepare herself for the able monopolar needle.
fall and unfortunately landed on her left elbow region.
Rest Activity
Immediately following the accident she experienced profound
Muscle PSW/Fibrillation Recruitment
pain at the elbow region with inability to feel the fourth and fifth
digits of her left hand as well as difficulty using her left hand.
(L) Abductor pollicis brevis o Normal
(L) First dorsal interosseous 2+ Reduced
As she had no difficulty skating and executing her skills she left
(L) Abductor digiti minimi 2+ Reduced
for a competition the next day. Within 2 days her localized
(L) Flexor digitorum profundus 2+ Reduced
elbow pain resolved, and the left hand numbness and weakness
improved. She was seen by a physician 3 weeks following the
(L) Flexor carpi ulnaris o Normal
initial insult. Radiographic examination of the left upper limb,
(L) Triceps o Normal
including the elbow, was normal. She was subsequently given a
(L) Cervical paraspinals o Normal
nonsteroidal anti-inflammatory medication, program of upper Summary of Findings.
limb rest, and referred for an electrodiagnostic medicine evalua 1. Normal neural conduction parameters of the left and right
tion 4 weeks after the initial elbow trauma. median sensory and motor nerves.
Physical Examination. On physical examination the patient 2. Normal neural conduction parameters of the right ulnar
demonstrated a minimal amount of tenderness about the left nerve.
medial epicondyle with no obvious signs of trauma. There was 3. The left ulnar nerve demonstrated a drop in amplitude
a mild Tinet's sign just distal to the medial epicondyle on the across the elbow region of 37%.
left. There is was also a slight decrease in sensation to touch, 4. The left compared to right ulnar nerve at the wrist reveals
pin prick, and temperature in the cutaneous distribution of the a 28% drop in amplitude.
left ulnar nerve including the dorsal ulnar cutaneous nerve. 5. There is a 28% drop in area across the left elbow region
Additionally, the flexor digitorum profundus and all hand in for the ulnar nerve CMAP.
trinsic muscles except the abductor pollicis brevis and opponens 6. Slowing of conduction for the left ulnar nerve across the
pollicis demonstrated a 3+/5 grade of strength on manual elbow region.
muscle examination. A normal grade of strength was docu 7. Membrane instability and reduced recruitment are present
mented in all remaining muscles of the left upper limb. Deep in the ulnar innervated muscles of the left upper limb below the
tendon reflexes in the upper limbs are symmetric bilaterally and innervation of the flexor carpi ulnaris.
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 145
Impression. The patient demonstrates electrophysioiogic DSL, distal sensory latency; S Amp, sensory amplitude; DML,
findings consistent with a combination of Wallerian degenera distal motor latency; M Amp, motor amplitude; NCV, nerve
tion and conduction block of the left ulnar nerve most likely lo conduction velocity; ms, milliseconds; !-lV, microvolts; mV, mil
cated about the left elbow region. livolts; mis, meter/second. Motor and sensory amplitudes are
Recommendation. The patient should rest the upper limb for measured baseline-to-peak. Sensory latencies are measured to
3-4 weeks and refrain from left upper limb strength training but peak while motor latencies are measured to initial negative
may continue to perform ice skating routines. The elbow should onset.
be well padded while skating to avoid injury should a fall occur. • Amplitudes and velocities across fully flexed elbow. AE,
A repeat study of the left ulnar nerve should be performed in ap above elbow; BE, below elbow.
proximately 3-4 weeks to monitor the nerve's electrophysiologic Needle Electromyograpby. A needle electromyographic in
status particularly with respect to conduction block. vestigation was performed on the left upper limb using a dispos
able monopolar needle.
Case #2
Rest Activity
History. A 46-year-old right-handed male with insulin-depen
Muscle PSWlFibrillation Recruitment
dent diabetes complains of numbness involving the fourth and
(L) Abductor pollicis brevis 0 Normal
fifth digits of the left upper limb for approximately 3 months. He
(L) First dorsal interosseous 1+ Mildly Reduced
states that he is not aware of any traumatic incident to the affected
(L) Abductor digiti minimi 1+ Mildly Reduced
limb that may have contributed to the problem, but that he does
(L) Flexor digitorum profundus I+ Mildly Reduced
have a habit of leaning on his left elbow. The numbness has been
(L) Flexor carpi ulnaris 0 Normal
slowly progressive in nature since starting a new job about 4
(L) Triceps 0 Normal
months ago that requires him to keep detailed ledgers of numbers.
(L) Cervical paraspinals 0 Normal
The patient also notes that he is having difficulty buttoning his
shirts with the left hand. No other medical complaints are noted. Summary of Findings.
Physical Examination. On physical examination the patient 1. Prolonged distal sensory latencis for the left sural, bilat
demonstrates decreased deep tendon reflexes of the biceps, triceps, eral median, and bilateral ulnar nerves.
and pronator teres of 1+12+ in both upper limbs. The knee and 2. Borderline nerve conduction slowing of the peroneal,
ankle reflexes are absent in the lower limbs bilaterally. There is a median, and ulnar nerves.
"stocking and glove" type of decreased sensation to touch, temper 3. Significant slowing of the left ulnar nerve across the
ature, and pin prick in the upper and lower limbs. Of note is that the elbow region.
cutaneous distribution of the left ulnar nerve is significantly more 4. The left ulnar nerve demonstrated a drop in amplitude
reduced compared to the other cutaneous regions of the upper and across the elbow region of 52%.
lower limbs tested. Manual muscle testing of the upper and lower 5. There is a 9.8% drop in area across the left elbow region
limbs reveals a 4/5 grade of strength, which is symmetric in the for the ulnar nerve CMAP.
upper and lower limbs except for the ulnar-innervated muscles of 6. Membrane instability and reduced recruitment are present
the left limb. The ulnar-innervated intrinsic and extrinsic muscles in the ulnar-innervated muscles of the left upper limb below the
demonstrate a 3/5 grade of strength. There is also mild wasting of innervation of the flexor carpi ulnaris.
the left first dorsal interosseous muscle compared to the same Impression. 1. The patient demonstrates electrophysiologic
muscle on the right. There are no upper limb root tension signs or findings consistent with a combination of Wallerian degenera
limited cervical motion. tion and conduction slowing of the ulnar nerve about the left
Nerve Conduction Studies. Nerve conduction studies are elbow region. The combination of increased temporal disper
performed in the upper limbs bilaterally. The mid-palm temper sion and decreased amplitude are suggestive of a demyelinating
ature is 32.0°C on the right and 32.5°C on the left. type of lesion at the elbow with some axonal loss. Additionally,
the drop in amplitude with a normal drop in area suggests that
DSL S Amp DML M Amp NCV
the amplitude reduction across the elbow is secondary to the
Nerve (ms) (J..lV) (ms) (mV) (m/s)
temporal dispersion and not a conduction block.
Left sural 5.1 5.0 2. There is electrophysiologic evidence to support the diag
Left peroneal 7.2 3.1 39.0 nosis of a mild generalized sensorimotor peripheral neuropathy.
Right median 4.2 20.0 4.2 8.0 50.0 This finding is consistent with the patient's history of diabetes
Right ulnar 4.1 15.0 4.0 7.0 51.0 mellitus and physical examination.
Right ulnar 7.0 (BE)' 54.0' Recommendation. The patient is instructed to avoid any
6.5 (AE)' type of compression to the left or right elbow region and to
Right ulnar CMAP (AE) duration: 7.5 ms maintain the ledgers in such a manner as to avoid further
Right ulnar CMAP (BE) duration: 7.1 ms injury to the left ulnar nerve. A repeat examination in 4-6
Right ulnar CMAP (AE) area: 28.3 mV-ms weeks is suggested to ensure that the lesion does not progress
Right ulnar CMAP (BE) area: 24.8 mV-ms further.
Left median 4.0 18.0 4.4 7.8 51.0
Left ulnar 4.3 8.0 4.5 6.5 48.0 Comment
Left ulnar 6.2 (BE)' 42.0' The above two cases illustrate a number of relevant issues re
3.0 (AE)" garding the electrophysiologic diagnosis of conduction block.
Left ulnar CMAP (AE) duration: 15.0 ms At first glance one may consider conduction block to be present
Left ulnar CMAP (BE) duration: 8.2 ms if the CMAP amplitude obtained proximal to a suspected site of
Left ulnar CMAP (AE) area: 27.5 mV-ms neural compromise is significantly reduced (greater than
Left ulnar CMAP (BE) area: 29.4 mV-ms 14-20%) compared to the amplitude just below the injury site.
146 - PART I FUNDAMENTAL PRINCIPLES
On the other hand, axonal loss results in amplitude reduction at can conclude that the same area, above and below the elbow,
all stimulus locations proximal and distal to the site of does not suggest a dropout of fibers, i.e., pseudo-conduction
injury.37.224.317 This is because the recording electrode is typi block. 222 The amplitude is reduced, therefore, secondary to the
cally located on an end organ such as skeletal muscle and marked increase in temporal dispersion of the nerve fibers con
Wallerian degeneration has rendered a number of motor units ducting across the elbow region. Increasing the range of con
nonfunctional and thus incapable of generating an action poten duction velocities across a region acts to decrease. the
tial. If proximal compared to distal focal amplitude reductions synchronous arrival of the action potentials at the end organ. A
were the only criteria used to diagnose conduction block, a less synchronous arrival of action potentials means that there is
number of patients would be misdiagnosed. The reason for this less "in-phase" summation of similar waveform aspects thereby
erroneous conclusion is that a reduction in amplitude can arise leading to phase cancellation and amplitude reduction. The
from another common occurrence besides conduction block, second patient's combination of amplitUde, area, and duration
i.e., temporal dispersion. data strongly suggest that the drop in amplitude across the
In Case I there is an obvious inciting traumatic incident most elbow is not a result of conduction block, but an increase in
likely producing the patient's complaint. Electrophysiologic eval temporal dispersion secondary to an elbow lesion, i.e., demyeli
uation reveals that the CMAP for the left ulnar nerve above com nation. This is also supported by the slowing in conduction
pared to below the elbow demonstrates a 36.5% amplitude across the elbow. In Case I, the slowing of elbow conduction is
reduction while the area increases 28.0% (larger distal compared most likely a result of blocking of the fastest fibers with only
to proximal stimulation sites) and the duration decreases 3.3%. the more slowly conducting fibers reaching the end organ, i.e.,
The ulnar CMAP at the wrist on the affected compared to unaf hypothenar muscles. In this instance. one is essentially compar
fected side reveals a 27.0% amplitude reduction. Case 2 shows ing two fiber populations to arrive at a conduction velocity. This
that the amplitude reduction across the elbow is 51.6% while area practice is of questionable value as one should not compare two
changes by only 6.4% and duration changes by 45.0%. There is a different fiber populations to arrive at a value supposedly repre
7.1 % difference between the CMAP on the symptomatic com senting the "fastest" -conducting fibers. Additionally, in Case I
pared to asymptomatic hand. These results demonstrate the con there is both CMAP (left vs. right wrist amplitude difference of
fusion possible when attempting to diagnose conduction block. 27.0%) and needle electromyographic evidence of axonal loss.
The drop in amplitude across the elbow region for the two pa The concept of phase cancellation is important and should be
tients is certainly significant and more than the 13.6% ampli understood to better comprehend the underlying mechanism
tude change possible in normal individuals (Table 4_6).223.224 producing changes in amplitude so that the distinction between
Specifically, the first patient has a 36.5% reduction and the conduction block and temporal dispersion can be made. A
second individual a 5l.6% amplitude decline. These findings simple yet elegant demonstration serves to clarify the interac
are both suspicious for a lesion producing conduction block. tion of single nerve fibers and motor units with respect to sen
The important aspect is to confirm this tentative impression. Of sory nerve action potentials (SNAPs) or muscle action
note is the difference in duration and area changes for these two potentials amplitude, duration, and area. 11I If one records an an
individuals. In the first compared to the second patient, there is tidromic SNAP from the digit and stimulates the median or
an abnormal change in area, i.e., 28% vs. 6.4%. Additionally, ulnar nerve at progressively more proximal locations (from
the duration for the across-elbow potential is normal in the first wrist to axilla), a number of characteristic changes in the wave
(3.3%) but abnormal in the second (45.0%) patient. The combi form are noted (Fig. 4-17). Specifically, the duration increases
nation of area and duration changes suggest that there is little
temporal dispersion of action potential conduction across the Ulnar Nerve Stimulation
first patient's elbow, while there is significant temporal disper
sion in the second patient. Using the normal criteria for ampli
tude, duration, and area, it is possible to distinguish the
individuals with abnormal amplitude reductions over a particu
lar anatomic region who have sustained conduction block
versus temporal dispersion (Table 4-6). The ulnar nerve CMAP
amplitude change in Case 1 is a result of conduction block be
cause the duration of the potential is comparable to that antici
pated in normal individuals. The reduction in area, however,
implies that there is a dropout of fibers that are incapable of
contributing to the CMAP amplitude. This combination of
normal duration with an abnormal area reduction is highly sug
gestive of conduction block. On the other hand, Case 2 reveals
an ulnar CMAP across the elbow with both an amplitude drop
and duration increases, but little change in area. As a result, one
Table 4·6. Ulnar Nerve Quantitative CHAP Waveform Figure 4-' 7. Ulnar nerve stimulation. Stim'llation along the
Parameterssa, I 10 course of the ulnar nerve with simultaneous recording of the CMAP
from the hypothenar eminence and the fifth-digit SNAP. Note that the
Percent Change CMAP changes little with proximal stimulation while the SNAP demon
Location Amplitude (mY) Area Duration (msec) strates significant decreases in amplitude and area, but an increase in
Above elbow-wrist 19.2 16.0 15.0 duration. (From Kimura J, Machida M, Ishida T, et al: Relation between
size of compound sensory or muscle action potentials. and length of
Above elbow-below elbow 13.6 6.7 8.3
nerve segment. Neurology 1986;36:647-652, with permission.)
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 147
dramatically and in some cases doubles while the amplitude and Summated
area are reduced by about 50%. On the other hand, the CMAP response
duration may increase only 6.0-8.0% with amplitude and area
declining approximately 10% over comparable distances.
The above findings are understandable if one recognizes that
biphasic initial1y negative potentials are recorded for both sen
sory and motor studies in most routine surface techniques. The .. ,
negative spike duration of the single-fiber sensory potential is
approximately 0.5 ms, which is about 50% of the corresponding
s--:-o-9l'1i ....
J
\.1---"
SNAP. There are thousands of biphasic single-nerve action p0
tentials with a range of conduction velocities between the
fastest and slowest approaching 25 rnls.12,73 Thus, there is signif
icant overlap of the positive spike of the first-arriving action p0
tentials with the negative spike of those traveling more slowly.
This positive/negative phase overlap results in cancellation of
these aspects of the waveforms, thereby reducing the amplitude ..
(Fig. 4-18). When the nerve is excited at more proximal loca
tions, the disparity of arrival at the recording electrode is magni
fied because of the 25 mls conduction differential. The Jess
S'""":"t-...:·1f~~ I........ j \rm
synchronous arrival of individual action potentials produces Figure 4-18. SNAP obtained with distal stimulation.There is a
considerably more phase cancellation as there is increased over certain amount of phase cancellation secondary to the disparity be
lap of the positive phases from the faster-conducting axons with tween the Single-fiber and composite potential's duration. Increasing
the negative phases of the slower-conducting axons. The net the distance between stimulation and recording sites results in signifi
result of this increased phase cancellation with progressively cantly more overlap secondary to the temporal dispersion of fastest·
more separation between the stimulating and recording elec compared to slowest.conducting fibers. This lead to phase cancellation
trodes is a reduction in amplitude and area with an increase in resulting in a potential with smaller amplitude and area but larger duo
duration. Therefore, temporal dispersion has profound effects, ration. (From Kimura J, Machida M, Ishida T, et al: Relation between size
even in normal sensory nerve, with respect to the waveform pa of compound sensory or muscle action potentials, and length of nerve
rameters. This finding of dramatic alterations in sensory wave segment. Neurology 1986;36:647~S2, with permiSSion.)
forms reduces the diagnostic applicability of sensory potentials.
As noted in the above two cases, the sensory potential findings
are essentially ignored when attempting to define conduction (see Chapter 2). The individual motor unit action potentials
block over relatively large segments of the peripheral nervous have a negative spike duration approximating 5-6 ms.
system such as above elbow-to-wrist or digit recordings. Coincidentally, the duration of the CMAP also has a negative
A significantly different situation is found for CMAPs with spike duration of 5-6 ms. As a result, the single motor units are
respect to phase cancellation and hence diagnostic utility re primarily in phase when they are generated. This is a com
garding the differentiation of conduction block from temporal pletely different mechanism from the SNAP as there is a tempo
dispersion. Recall that the CMAP is the three-dimensional sum ral component of arrival at the recording electrode combined
mation of individual biphasic motor units contained within the with a significant disparity between the SNAP and the individ
muscle. These motor units are biphasic negative-positive be ual action potential duration. In muscle, there is little phase can
cause they are recorded from the end-plate region and hence cellation with distal stimulation because of the similarity
originate beneath the recording electrode and propagate away between the individual and summated negative spike durations.
F S>-----:~:-If~~
S ~~~-----'v-{f;lf1) ~
Ii
;
....
. . ."..
..... f
..
.' . .
_"
.'
____ . .
F ~htr---+.~)
S If!.-..t----ftI~)
Figure 4-19. Compound muscle action potentials. Unlike the SNAP. the single-fiber motor unit action potential and CMAP have simnar dura·
tions creating a greater tolerance for any phase overlap, thus minimizing phase cancellation. Additionally, there is half the temporal dispersion for the
same distance resulting in little alteration in the CMAP between proximal and distal stimulation sites. (From Kimura j, Machida M, Ishida T, et al:
Relation between size of compound sensory or muscle action potentials. and length of nerve segment. Neurology 1986;36:647~52, with permission.)
148 - PART I FUNDAMENTAL PRINCIPLES
With more proximal stimulation, there is only a small fraction result from compression, but nevertheless profoundly affect
of the phase cancellation compared to the sensory potential be peripheral nerves. These conditions can be classified as entrap
cause there is only half the amount of disparity (12-13 mlS)72.73 ment neuropathies (Table 4-7). Although a complete discus
between the fastest- and slowest-conducting motor fibers as that sion of the various types and clinical presentations of
noted for sensory fibers. The combination of similar negative entrapment neuropathies is not presented in this chapter, the
spike durations for single and compound potentials plus half the basic pathophysiology and histologic appearance of compres
temporal dispersion results in the single motor unit action po sion is considered. As with acute compression neuropathies, it
tentials maintaining their "in-phase" relationship with little is difficult to perfonn histologic investigations on humans with
decrement in amplitude or area and minimal increase in dura known chronic nerve entrapment syndromes. Animal models
tion (Fig. 4-19). Because of small changes in the above three demonstrating similar pathology to that known to exist in
parameters, CMAP quantification is much more reliable diag humans is the most acceptable alternative.
nostically than the sensory nerve action potential. The concept Fortunately, an animal model of chronic nerve compression
of phase cancellation has been shown to be the most likely ex naturally occurs in the guinea-pig. In guinea-pigs aged 2 years
planation of the noted findings with respect to negative spike or older, there is known to exist a progressive compression of
amplitude, duration, and area changes by various computer the median and ulnar nerves at the wriSt. 9•IOO Histologic sections
modeling programs. 253 It should now be clear why only the of the median nerve distal, across, and proximal to the wrist in
CMAP was used in the above two case examples to assess the older animals were compared with younger specimens to assess
presence of conduction block. the amount of demyelination present. Two basic categories of
The quantitative use of CMAP area, duration, and amplitUde lesions were noted. The first consisted primarily of demyeli
appears to be rather important when the question of quantifying nated fibers at the wrist with little or no degenerative changes
conduction block arises. Unfortunately, the above CMAP para due to Wallerian degeneration. The fiber content of both large
meters have not be collected for all nerves routinely examined. (greater than 6 !lm in diameter) and small (2-5 !lm diameter)
It is the practice to generalize the findings noted in the upper nerves proximal to the wrist were unchanged. In other words,
limb to lower limb nerves;37 however, it is most appropriate to demyelination at the wrist without Wallerian degeneration does
first develop nonnative parameters prior to assuming that upper not lead to fiber loss proximal to the lesion. The second cate
and lower limbs are identical. gory of nerve lesion was found in the majority of the oldest ani
mals where the previously noted demyelination at the wrist had
progressed to Wallerian degeneration. In this instance, the fiber
CHRONIC NERVE COMPRESSION distribution of nerves well proximal to the wrist demonstrated
essentially little, if any, loss of the small fibers, but at least a
The previous discussions have primarily considered the ef 50% reduction in large fiber content. This is consistent with pre
fects of acute lesions on the peripheral nervous system. There vious work in which sectioning of the nerve with ensuing
are certainly a large number of conditions that are chronic and Wallerian degeneration resulted in reduced diameter and num
bers of nerve fibers proximal to the lesion site, most likely aris
ing from the reactive neuronal cell loss. The importance of the
Table 4-7. Chronic Nerve Compression/Entrapment finding in the guinea pig model is that chronic compression that
Syndrome Etiology causes Wallerian degeneration can produce changes in the fiber
content proximal to the site of the lesion. Unlike acute compres
I. Compression in a Fibro-Osseous Tunnel
sive lesions, the histologic appearance of nerves subjected to
Carpal tunnel syndrome Median nerve compression at wrist
chronic compression is quite different.
Cubital tunnel syndrome Ulnar nerve compression at elbow
Recall that in acute compressive lesions there is invagination
Canal of Guyon Ulnar nerve compression at wrist
of one paranodai region into the next with a polarity such that
Supinator syndrome Radial nerve compression mid
the direction of intussusception is directed away from the two
forearm in or about supinator muscle
edges of the cuff. A quite different type of lesion in the guinea
Meralgia paresthetica Lateral femoral cutaneous nerve com
pig is noted for chronic lesions. 198,220 Specifically, for distances
pression about anterior superior iliac
approximating 20 mm proximal to the wrist there is a sequential
spine
tapering of myelin for each internode region toward the lesion.
Tarsal tunnel syndrome Mediaillateral plantar nerve compression
The opposite end of the internode reveals a bulbous accumula
in foot
tion of myelin. This finding also occurs distal to the compres
II. Angulation and Stretch sion site. The bulbous end consistently pointed away from the
Tardy ulnar palsy Ulnar nerve deformed at elbow wrist region whether proximal or distal to the wrist. This polar
Thoracic outlet syndrome Angulation of lower trunk/medial ized anatomic distortion is described as a series of tadpoles on
cord of brachial plexus over cervical either side of the lesion aligned head-to-tail, with the tails di
rib or band rected toward the lesion (Fig. 4-20).221 In younger animals there
III. Recurrent External Compressive Force is an asymmetry of myelin only. As the animals age, the tadpole
Ulnar nerve at elbow Leaning on exposed ulnar nerve at lesion becomes more apparent, eventually progressing to de
the elbow with forearm pronated myelination beneath the compressive zone with remyelination.
Deep branch of ulnar nerve Repetitive trauma, e.g., carpet laying In very advanced lesions, Wallerian degeneration is observed to
in hand with implement to secure carpet
occur in the demyelinated zone.
under molding
Electron microscopy reveals the fine details of this anatomic
Modified from Gilliat RW: Chronic nerve compression and entrapment. In distortion and suggests a possible mechanism.19s.222 The abnor
Sumner AJ (ed): The Physiology of Peripheral Nerve Disease. Philadelphia, w.e. mal appearance of the myelin proximal and distal to the com
Saunders, 1980, pp 316-339. pressed region suggests that there is slippage of the internal
Chapter 4 PERIPHERAL NERVOUS SYSTEM'S REACTION TO INJURY - 149
cc:::=-==..~(c:=::~===~~(=::~-==...--==-:::::Jt.. ====:)..-====Z)~
figure 4.20. Chronic compression. A. Depiction of guinea A
pig nerve showing distortion of the myelin segments. The polar
ity of the distortion is reversed at the wrist region. B,
Continued anatomic distortion with a region of demyelina
-
e=
=
tion/remyelination beneath the carpal tunnel area as demon ::::(
strated by the small and increased number of internodes. C, B
Advanced lesion with Wallerian degeneration present. (From
Ochoa J: Nerve fiber pathology in acute and chronic compres
sion. In Omer GE, Spinner M (eds): Management of Peripheral
Nerve Problems. Philadelphia, VY.B. Saunders, 1980, pp 487-50 I.
with permission.)
e=-...... .c=:=,............-
...... ---.. < -.....
-.~.~------ ------ ...........-
__.....,., ...--------...
•••
C -----
myelin lamellae. This slippage is directed away from the lesion, largest myelinated fibers are affected first and to the greatest
thus accounting for the thinning or tadpole tail. As one pro degree in compressive lesions. 198 The pathologic basis for this
gresses toward the lesion site, the amount of myelin thinning in slowing of latency and conduction velocity is the observed de
creases to involve more of the internode. This myelin is myelination in the large myelinated and fast-conducting fibers,
subsequently "pushed" toward the opposite paranodal region, Stimulation of the median nerve during operative intervention
thus accumulating in this area and generating the bulbous end. for carpal tunnel syndrome reveals that there is slowing of con
At the bulbous paranodal site there is buckling and splitting of duction across the carpal tunnel with conduction block in about
the myelin (Fig. 4-21). 25% of fibers. ISO This finding suggests that patients who experi
The constant and repetitive compressive forces are believed to ence significant weakness most likely have had Wallerian de
generate pressure waves. The pressure waves are produced in the generation to account for this loss of muscle power. By
central regions of the compression zone and are directed both continually investigating the conduction velocity of both sen
proximal and distal to this site decreasing with distance (Fig. 4 sory and motor fibers during and after operative intervention, it
21). These directed forces then act on the nerve to "push" the is possible to determine the course of recovery for the injured
myelin away from the central regions of the entrapment. Directly nerves. Intraneural microelectrode studies have demonstrated
beneath the constricting zone there is complete demyelination that within a few minutes of surgical release previously blocked
and eventual Wallerian degeneration. On either side of the of sensory fibers begin to function,44,187 Additionally, within three
fending lesion are the progressive distortions of myelin sequen months of carpal tunnel release many patients demonstrate sig
tially tapering and buckling less and less as distance from the nificant increases in conduction velocity both distal and across
lesion increases. Unrolling the myelin sheath would reveal a dis the affected neural segment. This finding suggests that the re
placement of the inner lamellae (Fig. 4-21). In support of the ap covered nerves most likely had experienced conduction block
plicability of this model in man is the histologic finding of and/or segmental demyelination, which is within the time frame
similar anatomic distortions involving the median nerve at the of recovery. This rapid rate of recovery rules out regeneration of
wrist and ulnar fibers at the elbow,137,21().211 and the lateral femoral previously denervated nerves.
cutaneous nerve about the inguinal ligament. ls7 A further interesting observation is the slowing of motor nerve
In humans there is ample electrophysiologic evidence for conduction proximal to the presumed lesion site in compressive
conduction delay or slowing, conduction block, ectopic impulse syndromes, especially the carpal tunnel syndrome. 9,99,100.286 One
production, and Wallerian degeneration in chronic nerve entrap should not conclude that this finding is exclusively indicative of
ment syndromes.36.39.40,15o.168,286 The distal motor latency and retrograde degeneration proximal to the site of the lesion, e.g., in
conduction velocity are assessed by measuring the fastest-con carpal tunnel the median nerve for some undefined reason de
ducting motor fibers. It has been clearly demonstrated that the generates into the mid- or proximal forearm. There is no question
Table 4-8. Toxins Producing Peripheral Nerve system can be involved. Large decreases in neural conduction
Degeneration velocity can result from segmental demyelination depending
I. Industrial Chemicals upon the extent of the lesion. 76,78.287,288 In particular, patients
A. Affects Peripheral Nervous System Preferentially with chronic familial demyelinatinglremyelinating neuropathies
Lead can have conduction velocities approaching 5 mls or less.
Acrylamide Decreased conduction velocity, therefore, is a hallmark of a pro
Organophosphates found demyelinating process affecting the peripheral nerve. If
Thallium the particular process results in demyelination affecting some
B. Some Effects on Central Nervous System fibers more than others over a particular portion of the nerve,
Carbon disulfide one can anticipate not only a decrease in the conduction veloc
Methylmercury ity but also a reduced amplitude and a dispersed potential. This
Methylbromide is a result of the disparate slowing of conduction for multiple
C. Large Amounts Required fibers, thus leading to a marked increase in temporal dispersion
Arsenic with an associated reduction in potential magnitude.
Trichloroethylene
Tetrachloroethane MOTOR AND SENSORY NEURONOPATHY
2,4-0 (Dichlorophenoxyacetic acid)
Pentachlorophenol A number of disease processes or toxins directly attack the
DDT cell bodies of the peripheral nervous system. These are often re
D. Some Effects on Other Than Nervous Tissue stricted to either the motor or sensory neurons although an over
Carbon Tetrachloride lap can occur. Motor neuron diseases are well known examples
Carbon Monoxide and generally result in selective loss of motor neurons. Usually
these are sporadic cases (amyotrophic lateral sclerosis) of un
II. Pharmaceutical Substances
known cause. Other possible causes are monomelic spinal mus
Amiodarone Hydralazine
Antinucleosides Isoniazid
cular atrophy, paraneoplastic syndromes, radiation damage or as
Arsenic Nitrofurantoin
part of a more generalized degenerative neurologic disease,
such as different types of dementias. 4 ,136.143,241.255 Viral invasion
Chemotherapeutic agents Phenytoin
Chloroquine Sulfonamides
also can result in motor neuronopathy (herpes zoster or po
liomyelitis).83,131 The result is a global Wallerian degeneration of
Colchicine Thalidomide
Disulfiram Thallium
the entire axon following the death of the cell body, Elec
trophysiologically, this results in findings compatible with pure
Gold Vitamin intoxication
motor axonal loss without a proximal-distal distribution. In
Modified after Gilliatt RW: Recent advances in the pathophysiology of nerve ALS, for example, the sensory conduction and amplitudes
conduction. In Desmedt JE (ed); New Developments in Electromyography and
Clinical Neurophysiology. Basel. Karger. 1973, pp 2-18. remain normal, the motor conduction is only slightly affected,
and the CMAPs diminish in amplitude. Needle EMG shows a
combination of de- and reinnervation besides fascicula
regeneration of at least some of the lost axons. Provided the in tions. 35 ,255 In addition to the peripheral loss, there is a central
dividual has not ingested too large a quantity of the toxic mater component due to the involvement of the upper motor neuron.
ial and is capable of reconstituting the injured nerves, one can The sensory neuronopathies are a less well known, heteroge
anticipate the expected findings based on what is known from neous, and not well understood group of disorders. A selective
nerve repair after degeneration. Because the endoneurial tubes targeting of the primary sensory neurons in the dorsal root gan
were not destroyed by the toxic substance, aberrant regenera glia is found. 121 The etiology ranges from paraneoplastic, toxic,
tion should be absent. The proliferation of Schwann cells with immune-mediated to viral.12.121.324 The onset can be acute with
axonal regrowth is the expected result. Recall that the conse extensive sensory loss of all kinds of modalities within several
quence of regeneration is smaller internodal distances with thin days to insidious and slowly progressive over many years (Table
ner myelin sheaths, particularly early after the nerve is 4-9), The acute cases usually have prominent dysesthesias. 2()7
regenerated. As a result, even though the initial conduction ve Often a special class of neurons is affected, for example the
locities are little affected, once the nerves have degenerated and large-diameter neurons resulting in sensory ataxia, propriocep
undergone repair, a reduction in conduction velocity over the af tive disturbances and areflexia. The paraneoplastic sensory neu
fected segment may be observed with normal conduction proxi ronopathy associated with small-cell lung cancer is due to a
mally. For nerves experiencing only distal degeneration, a circulating anti-Hu antibody,207 In rare cases a combination of a
prolonged distal motor latency with possible dispersion of the sensory neuronopathy can be seen, and a demyelinating neu
evoked response may be observed.IOl,l4/) ropathy complicating diagnosis further. 11 In an animal model of
toxic sensory neuronopathy, it was found that megadoses of
EXTENSIVE SEGMENTAL (GENERALIZED) pyridoxine resulted in disruption of the cell metabolism fol
DEMYELINATION lowed by degeneration of the entire axons. 182 Megadosis of pyri
doxin in humans is also known to result in a severe, acute
In addition to the focal segmental demyelination caused by sensory neuronopathy.7
compression or entrapment, more extensive segmental demyeli Important findings in electrodiagnostic studies are a decline
nation can result from a number of disease processes. These in sensory amplitudes concomitant with the clinical course and
processes are associated with various peripheral neuropathies loss of H-reflexes. The distribution is not compatible with a
resulting from varied etiologies (Table 4-8). Comparatively length-dependent axonopathy. Often generalized absent sensory
more or quite extensive portions of the peripheral nervous responses are found. The motor conduction velocities and
152 - PART I FUNDAMENTAL PRINCIPLES
Table 4-9. Rate of Evolution of Sensory Neuropathies and 15. Barr ML, Hamilton JD: A quantitative study of certain morphological changes
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Rate of Evolution male and female, and the behaviour of the nucleolar satellite during accelarated
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Neurosurg Psychiatry 1977;40:50-57. 326. Wright EB: The effects of asphyxiation and narcosis on peripheral nerve polar
292. Trojaborg W: Early electrophysiologica1 changes in conduction block. Muscle ization and conduction. Am J Physiol 1947;J48:174-184.
Nerve 1978;1:400-403. 327. Young JZ: The functional repair of nervous tissue. Physiol Rev 1942;22:318-374.
293. Uchida Y. Sugioka Y: Electrodiagnosis of retrograde changes in carpal tunnel 328. Young IZ: Contraction. turgor and cytoskeleton of nerve fibres. Nature
syndrome. Electromyogr Clin Neurophysiol 1993;33:55-58. 1944;153:333-335.
294. Van Gehuchten A: Le phenomene de chromatolyse consecutif a lesion pathologique 329. Zelena 1: Neurofilaments and microtubules in sensory neurons after peripheral
ou experimentale de I' axone. Bull Acad Roy Med Belg 1897;11 :805-821. nerve section. Z Zellforsch Mikrosk Anat 1971 ;117:191-211.
PART
II
BASIC AND
ADVANCED
TECHNIQUES
Chapter 5
Historical Aspects of Nerve Conduction Common Upper Limb Nerve Conduction Studies
Upper Umb Motor Nerve Conduction Studies
Structure of the Peripheral Nervous System • Median Nerve • Ulnar Nerve • Radial Nerve • Phrenic
Unmyelinated Nerve Fibers • Myelinated Nerve Fibers Nerve
• Axonal Transport Mechanism • Periaxonal Region Upper Umb Sensory Nerve Conduction Studies
• Internodal Schwann Cell/Myelin Sheath • Nodes of Median Nerve • Ulnar Nerve • Dorsal Ulnar Cutaneous
Ranvier • Peripheral Nerve Structure • Action Nerve • Superficial Radial Nerve • Lateral Antebrachial
Potential Generation • Compound Nerve Action Cutaneous Nerve • Medial Antebrachial Cutaneous Nerve
Potential • Comparative NCS of Dual-Innervated Digits
Between 1850 and 1870, Von Helmholtz and associates deter size of the unmyelinated fiber, which necessitates electron as
mined the median nerve to have a conduction velocity of 61.0 ± opposed to light microscopy and demanding techniques to in
5.1 mls by using neural stimulation combined with measuring vestigate various electrophysiologic properties. Electron mi
the onset of the ensuing muscular contractions.345.346.347 Using croscopy, however, reveals a number of interesting structural
different methods, they also estimated sensory nerve conduction properties of unmyelinated nerve fibers.
to approximate 60 m/s..144 Major contributions to the determina The cell body of an unmyelinated nerve fiber is usually, lo
tion of neural impulse propagation were achieved in the 1920s cated at some proximal location within the central nervous
by Erlanger and Gasser89 .90 when they stratified conduction ve system or paravertebral ganglia. The peripheral extensions of
locities according to nerve fiber diameter. Further refinements these cell bodies extend to their end organ ensheathed by con
in both technique and instrumentation allowed motor nerve con secutively aligned satellite cells, i.e., Schwann cells. Unmy
duction velocities to be applied diagnostically by Hodes et al. in elinated nerve fibers usually consist of collections of multiple
1948. m.J39 With the development of instruments by Dawson 60 axons, each surrounded by a single column of Schwann cells. A
that could average multiple responses, sensory nerve conduc Schwann cell has numerous depressions within which a single
tion studies became practical clinically. Further refinements in peripheral axon is contained (Fig. 5-1). The size of unmyeli
the stimulating and recording apparatus presently permit exami nated nerve fibers ranges from 0.5 to about 2.0 l..Im. 201 Although
nation of the peripheral nervous system with good diagnostic a negative descriptor, unmyelinated nerves are axons whose
success. associated satellite Schwann cells do not normally produce an
enveloping multilayered proteophospholipid substance called
STRUCTURE OF THE PERIPHERAL NERVOUS SYSTEM myelin (see below). Developmentally, however, all axons are
initially unmyelinated. Also, there are distinct regions of myeli
The peripheral nervous system can be divided into two major nated nerves that are always unmyelinated, i.e., nodes of
classes of nerves: myelinated and unmyelinated. In this discus Ranvier, adjacent to the cell body (axon hillock), and near a
sion, unmyelinated nerves are only considered from the per motor nerve's termination at the neuromuscular junction.
spective of better understanding of myelinated nerves. The The actual structural relationship between the above noted
rationale for concentrating primarily on myelinated nerves is small axons and the Schwann cell may be imagined if a simple
that the more routine nerve conduction techniques exclusively model is considered. Let us first imagine the Schwann cell as a
assess conduction in the fastest myelinated nerve fibers. Minor two-dimensional object similar to a circle with a malleable
consideration is given to the more slowly conducting autonomic outer membrane boundary. The axon is then pressed against this
nerve fibers and techniques to examine their conduction proper boundary forming a cleft in the circle surrounding the axon.
ties at the end of this chapter. Continued pressure of the axon results in the intact outer mem
brane now completely surrounding the axon. At the circle's
Unmyelinated Nerve Fibers original point of invagination, a double-layered membrane is
The designation "nerve fiber" is understood to apply to the now formed that gives the appearance of the axon being sus
axon and its enveloping satellite cells.329 Information pertaining pended from the edge of the cell's outer boundary. This "sus
to unmyelinated nerve fibers, particularly regarding biologic pensory" region of cell membrane is known as the mesaxon and
processes, is less available than that for myelinated nerves. The is derived from the term designating the gut's mesentary (Figs.
reason for this relative paucity of information is the rather small 5-1 and 5-2). Additional axons share the same Schwann cell. In
the living organism, the Schwann cell most likely develops with
the growing axon and envelops the multiple axons it is destined
to support.
consists of smaller and more centrally located tubes. The sec extend along the entire internode.237.283.288 Schmidt-Lanterman
ondary aspects of the sarcoplasmic reticulum have been pro incisures (see below) are also isolated from the periaxonal
posed to be the source of synaptic vesicles. Ribosomes can be region.
detected in the more distal regions of the axoplasm and at
times associated with the endoplasmic reticular structures. 329 Internodal Schwann Cell/Myelin Sheath
The sarcoplasmic reticulum is believed to be one of the axon's It is suggested that there are a fixed number of Schwann c.ells
transport mechanisms. 76.77 associated with each myelinated nerve fiber at the beginning of
A number of vesicular structures are located within the axo development such that axonal growth is accompanied by elon
plasm. Chain-like composites of clear vesicles are often ob gation of the Schwann cell and its cytoplasmic territory.287.342
served near the nodes of Ranvier. II •I99 Lysosomes are typically The territory of individual Schwann cells defines the internode
identified along the length of most axons.145.300 Near the nodes length and ranges from 200 J..lm to 2,000 J..lm with a direct corre
of Ranvier, endocytotic "coated" vesicles are found and have lation between axon diameter and an internode's spatial ex
been postulated to constitute a mechanism whereby extracellu panse.199.327.359 Although the internodal length can vary
lar substances are incorporated into the axon and subsequently substantially from one axon to the next, the internodal distance
distributed through the smooth endoplasmic reticulum's trans for anyone nerve is relatively constant.
port system.249.295 Schwann Cell. The Schwann cell may be best considered if
it is thought of as unfurled from its axon similar to the unrolling
Axonal Transport Mechanism of a flag (Fig. 5-3). The flat trapezoidal Schwann cell can now
An obvious observation regarding axons is that their cell be appreciated with respect to its constituent parts. That region
bodies give rise to a peripheral extension capable of reaching of the cell's cytoplasm comprising the first wrapping around the
more than one meter in length with an accompanying axoplas axon (adaxonal) is referred to as the inner belt, while the su
mic mass significantly exceeding that of the cell body. How perficial aspect of the cell (abaxonal) containing the nucleus
does the cell body sustain the metabolic requirements of its pe and nodal villi is known as the outer belt. A less dense or semi
ripheral process? This relatively simple question has resulted in compact myelin is found in both of these areas. The compact
a number of transport mechanisms being postulated that carry myelin is located between the adaxonal and abaxonal regions. 238
various cellular materials in both directions.208.249 The or Connecting the inner and outer belts is a cytoplasmic pathway
thograde or somatofugal (away from the cell body) transport known as the Schmidt-Lanterman incisure.
systems may function at two and possibly five different rates In the adaxonal region one can observe that the Schwann cell
(0.25-3 to 400 mmJday) with one axonal protein being trans membrane and cytoplasm fonn a spiral of about one turn with
ported per system.1I9.356.357.360 Of note, the distally directed slow opposing Schwann cell plasma membrane fusing with the aid of
transport ofaxoplasmic mass movement approximating 0.25-3 tight junctions to form the inner me saxon (Fig. 5-2C). The
mm/day is about the rate of axonal regrowth following nerve Schwann cell cytoplasm in the adaxonal area contains a number
transection. 359 Generally, the retrograde or somatopetal (toward of membrane-associated particles of indetenninate function and
the cell body) axonal transport flow rates are roughly one-half no major cellular organelles. A similar fonnation of Schwann
of the orthograde flow rates. About 75% of the dry weight of the cell cytoplasm is fonned at the abaxonal region and contains a
transported material is accounted for in the fonn of tubulin and limited quantity of cytoplasm except for the perinuclear space.
neurofilamentous proteins traveling at the slowest rate of 0.25 As with the adaxonal spiral, an abaxonal cytoplasmic spiral
mm/day.16.143.208 Materials consisting of actin microfilaments exists that yields an outer mesaxon. Except for the perinuclear
with associated proteins and soluble enzymes traveling at 2-3 region, the outer plasmalemma of the Schwann cell is in close
mmJday make up the remainder of the transported substances. 16 approximation to the myelin sheath. Most of the Schwann cell's
Faster axonal transport rates require the expenditure of energy organelles, rough endoplasmic reticulum, Golgi membranes,
and are temperature-sensitive. 99 •loo The substances transported and mitochondria are gathered about its nucleus. Finger-like ex
at the relatively faster rates are glycoproteins, membranous sub tensions of the Schwann cell's membrane project into the node
components, and enzymes associated with the manufacture of of Ranvier region and are referred to as microvilli. Exterior to
transmitter substances. The actual mechanisms responsible for the Schwann cell's plasmalemma is a basal lamina investing
the faster rates of transport are unknown, but two postulates the entire nerve including the nodes of Ranvier.289
have been described. One of the transport systems is referred to Myelin Sheath. Close inspection through electron mi
as axoplasm streaming, which is thought to be a result of mi croscopy of the axon's myelin sheath reveals a continuous spiral
crotubular actin-myosin interacting with the transported sub of Schwann cell plasma membrane lamellae (Fig. 5-2C). These
stance through some type of interposed carrier system.249.276 lamellae are alternating layers of lipid and protein arising from
Support for this manner of transport is that multiple axoplasmic the Schwann cell "wrapping" its plasma membrane multiple
organelles are frequently noted to be in close association with times around the axon during the process of myelination. 111.276
microtubules and at times there appears to be a linkage between Myelin functions as an insulator for the axon allowing depolar
mitochondria and microtubules. The second type of fast axonal ization only at the regions devoid of myelin, i.e., nodes of
transport may occur within the tubular confines of the smooth Ranvier (see Chapter O. The presence of myelin, therefore,
endoplasmic reticulum. 77 causes the nerve to become depolarized at nodes of Ranvier, re
sulting in the action potential "jumping" from one node to the
Periaxonal Region next in the process of saltatory conduction. The velocity of
The periaxonal region is the space between the axolemma nerve conduction is directly related to the axon's diameter, in
and extracellular aspect of the Schwann cell's plasmalemma ap ternode length, and efficiency of myelin insulation. An optimal
proximating 20 nm. 329 This portion of the nerve is a self-con ratio of axon diameter to total fiber diameter has been postu
tained space and completely sealed from the Schwann cell lated to be 0.6.142.281 This theoretical ratio is often, but not
through mesaxon tight junctions (zona occIudens) which always, found in nature.
Chapter 5 NERVE CONDUCTION STUDIES - 163
Peripheral nervous system (PNS) myelin is composed of of ions, nutrients, and other small molecules through the com
lipids (e.g., sphingomyelin) and glycoproteins. The predomi pact myelin to the innermost layers of the myelin sheath and the
nant protein is myelin protein zero, Po, which accounts for ap axon itself. Connexin-32 also appears to be necessary for
proximately 50% of the total myeUn protein. Po is a 28-kD normal axonal structure and function. Mutations in the gene en
transmembrane protein that has an extracellular immunoglobu coding for connexin-32 located on chromosome Xp13 cause X
lin-like struture, a single transmembrane domain, and an intra linked CMT (see Hereditary Neuropathy chapter).
cytoplasmic tail. 302 It is believed that two Po molecules on Another major component of PNS myelin is myelin-associ
opposing surfaces of the myelin membrane interact at the inter ated glycoprotein (MAG).302 MAG localizes to periaxonal
period lines. 83 This interaction appears to be important in myelin sheath, noncompact myelin at Schmidt-Lanterman in
myelin compaction and stabilizing the major dense line. Of cisures, and paranodal terminal myelin loops. The protein is felt
note, mutations in the gene that encodes for Po located on chro to contribute to the stabilization of the myelin sheath. There are
mosome Iq22-23 can result in Charcot-Marie-Tooth disease no known mutations involving MAG. However, an acquired
type I B (CMTl B) or CMT3 (Dejerine-Sottas disease or con immune-mediated disorder associated with antibodies (usually
genital hypomyelinating neuropathy) (see Hereditary Neurop IgM) directed against epitope(s) on the MAG protein result in a
athy chapter). demyelinating sensorimotor polyneuropathy (see Acquired
Peripheral myelin protein-22 (PMP-22) is a 22-kD protein Neuropathy chapter).
that comprises 2-5% of PNS myelin protein. 302 The protein is A series of myelin basic proteins (MBPs) weighing 12-22
composed of four transmembrane domains, two extracellular kD account for approximately 15-20% of PNS myelin pro
loops, one intracellular loop, and two intracellular tails. PMP teins. 302 These proteins are also localized to compact myelin. A
22 localizes to the compact myelin, where, like Po, it is felt to 15-kD protein, named P 2 , comprises 1-14% ofPNS myelin pro
have a role in stablizing the myelin sheath. In addition, it ap tein. 302 Thus far, there are no known genetic or acquired periph
pears that normal expression of PMP-22 is required for in eral neuropathies related to abberant MBPs or P2 •
tegrity of the axon itself. As with Po, mutations involving the Schmidt-Lanterman Incisures. Schmidt-Lanterman in
gene encoding PMP-22 located on chromosome 17pl1.2 may cisures are direct cytoplasmic connections between the abax
result in CMT I A, hereditary neuropathy with liability to pres onal and adaxonal regions that penetrate the compact myelin
sure palsies (HNNP), or CMT3 (see Hereditary Neuropathy layer providing a cytoplasmic pathway within the Schwann cell
chapter). (Figs. 5-3 and 5-4). They may also extend for a short distance
Connexins are a family of gap junction structural proteins, involving only a few lamellae. These structures were initially
which are important in cell-to-cell communication. Connexin believed to be a result of artifacts created in the cell fixation
32 is a 32-kD myelin protein composed of four transmembrane process, but are now known to be vital regions of the living ceIL
domains.302 Six connexin-32 molecules oligomerize into a hexa The number of incisures is directly proportional to the thickness
merk structures on the Schwann celllamella. Connexin-32 is of myelin and can reach 25 incisures per internode in the
localized to the paranodal region and Schmidt-Lanterman in rat. 101,1 12,137 The incisures appear to be more prevalent in devel
cisures, where it forms intercellular channels that allow diffusion oping and remyelinating nerves following demyelination. Il3,137
164 - PART II BASIC AND ADVANCED TECHNIQUES
Figure 5-4. Myelinated nerve.A,Transverse section through a node of Ranvier with multiple Schwann cell microvilli projecting toward the ax
olemma. B, Schematic representation of a myelinated axon's paranodal region. Note how the axon is fluted and the surrounding myelin conforms
to the shape of the axon. The microvilli described above are also depicted projecting into the node of Ranver. C,A close drawing of a Schmidt
Lantermann inclsure.A microtubule is shown spiraling through the incisure. 0, The longitudinal section through a mouse myelinated nerve is
demonstrated with a Scmidt-Lantermann incisure. The drawing of the axon in the center of the diagram reveals how the distal paranodal region is
less bulbous than the proximal paranodal region with the proximal portion of the axon to the right. (From Williams PL,Warwick R, Dyson M,
Bannister LH (eds): Gray's Anatomy. Edinburgh, Churchill Uvingstone, 1989, p 900, with permission.)
Nodal Axon. The diameter of the axon narrows at the nodal The paranodal region of membrane has been suggested to be
region (nodal axon) and has been found to be reduced to one associated with action potential generation because a significant
third of the internodal area in the ventral and dorsal root fibers of concentration of sodium ions were found in the terminal loops
cats. The middle of the nodal axon, however, increases in size to of Schwann cell cytoplasm. 87,330 It is suggested that the terminal
result in the entire nodal axon appearing somewhat barrel loops are the source for the inward-directed sodium ions
shaped (Fig. 5_4).11.199 Additionally, the region of the axon through the nodal axolemma (see below). At the termination of
devoid of myelin approximates an area 20--25 11m2 or a distance an impulse, the sodium is pumped out of the axon through the
approaching 1.5 11m between the two internodes in large nodal axolemma and sequestered into the terminal loops by the
fibers.lI.m It has been demonstrated through freeze-fracture Schwann cell's microvilli, which extend into the nodal region,
teChniques that the axolemma contains on its outer surface a This postulate remains speculative and awaits further investiga
number of particles approximating a density of 1200/llm2 that tion (see below).
have been suggested to be sodium channels. 279.290 One also notes
an increase in the numbers ofaxoplasmic organelles such as en Peripheral Nerve Structure
doplasmic reticulum, lysosomal granules, glycogen, and, in par Typical peripheral nerves are structures consisting of individ
ticular, mitochondria in excess of five times that of the internodal ual nerve fibers arranged in a characteristic manner. Specifically,
axoplasm. The nodal axoplasm also has a more gelatinous con single nerve fibers are collectively arranged in large groups
sistency with comparatively higher amounts of sulfated and non known as funiculi (Fig. 5-6).324 Funiculi of different numbers
sulfated glycosaminoglycans. 2•204 Located within the boundaries and sizes may be observed in cross-section at any level along
of the basal lamina (the material covering the Schwann cell and the course of a nerve. Individual nerves and funiculi are invested
nodal region), axolemma, and paranodal myelin extensions is the and supported by connective tissue. Three distinct subcategories
gap substance. Although the composition and function of the of connective tissue have been identified in peripheral nerves:
gap substance is not completely known, it is believed to partici
pate in action potential generation.
Paranodal Region. An interesting observation may be made if EN
one considers the gross morphology of two adjacent internode re
gions in close proximity to the node of Ranvier, i.e., the paran
odaI region. There is an asymmetric paranodal enlargement of the
myelin sheath extending approximately 40 11m on either side of
the node (Fig. 5-4).133.213 Specifically, the myelin bulge is some
what larger on the proximal (closer to the cell body) than distal PE
side of the node with a distinct series of 3-6 indentations into the
bulbous myelin ends forming a crenated appearance when viewed
transversely (Fig. 5_4).269.329.358 The regions between the bulging
aspects of myelin are filled with Schwann cell cytoplasm contain
ing multiple mitochondria at 10--20 times the concentration in the
internodeY·358 Of note, the axon is fluted and surrounded by the
myelin, which conforms to its shape (Fig. 5-4). The terminal as
pects of the myelin lamellae tum acutely in toward the axolemma
to form out-pocketings or terminal cisternae of Schwann cell cyto
plasm (Fig. 5-4 and 5-5). These terminal loops of Schwann cell
cytoplasm are firmly adherent to the axolemma and their extent
defines the portion of the nerve referred to as the paranodal Figure 5-6. Nerve subcomponents. Diagrammatic representation
region.199.249 A few of the terminal loops do not reach the ax of a peripheral nerve with supporting connective tissue forming the
olemma. Additional cytoplasmic extension of the paranodal nerve's various subcomponents. Three individual fasciculi are shown.
Schwann cell plasmalemma forms several rows of microvilli that The surrounding epineurium (EP) invests the perineurium (PE), which
are directed in a radial fashion toward the nodal axolemma and forms the fasciculi of a peripheral nerve. The endoneurium (EN) ,sur
terminate in the gap substance of the node (Fig. 5-4 and 5-5). rounds individual axons within the funiculi.
166 - PART II BASIC AND ADVANCED TECHNIQUES
endoneurium, perineurium, and epineurium.324 Each axon is corrugated shape because the elastin fibers tend to shorten the
surrounded by an endoneurial sheath, where multiple axons nerve slightly, Positioning the limb where the joint angle
form the funiculi that in turn are invested by perineurial con stretches the nerve results in tension on the nerve. The nerve's
nective tissue. Multiple funiculi are invested by areolar connec undulations disappear as the slack previously present is re
tive tissue constituting the epineurium forming the peripheral moved. The epineurium's ability to endure stretching, however,
portion of the nerve proper. All three types of connective tissue is limited. Continued stretch placed on the nerve is further con
structures contain fibroblasts, collagen fibers, mast cells, and trolled by the funiculi unless their tensile strength is exceeded.
macrophages. Additionally, the perineurium contains mesothe It is believed that the epineurium with its component vessels
lial cells. and adipose tissue serves the function of cushioning and pro
Epineurium. A considerable amount of areolar connective tecting the individual nerve fibers. 324
tissue surrounds the individual funiculi defining a peripheral nerve Perineurium. Contained within the epineurium are individ
(Fig. 5-6). At the surface of the peripheral nerve this areolar con ual funiculi defined by an investing connective tissue condensa
nective tissue condenses to form a well-delineated connective tion composed of three distinguishable layers (Fig. 5-6).322 The
tissue sheath lending a specific limiting structure to the nerve. At outermost or external layer of connective tissue forms a smooth
regions of the nerve where individual branches arise, the transition from the well organized and defined perineurium with
epineurium forms clearly demarcated connective tissue condensa smaller and tightly arranged collagen fibers to the less dense
tions extending for some distance proximal to the site of the epineurium of larger and less organized collagen fibers. An in
branch's departure from the main nerve trunk. Within the termediate layer has a recognizable layer of lamellated flat per
epineurium and surrounding the individual funiculi are adipose ineurial cells. The innermost or internal layer consists of a
cells and elastin fibers. 103, 104 The amount of adipose tissue some single row of rather flat perineurial cells bound together with
what depends on the overall body fat content and is highly vari tight junctions. A potential subperineurial space separates the
able from one nerve to another. Adipose cells are rarely found in innermost aspect of the perineurium from the endoneurium.
any other portio~ of a peripheral nerve, i.e., endoneurium or per This inner layer is believed to be responsible for the "diffusion
ineurium. Also contained within the epineurium are nutrient blood barrier" of peripheral nerves. 278,293
vessels and lymphatics. The total amount of epineurium at anyone The perineurial sheath of motor fibers does not extend all the
location along the peripheral nerve is highly variable but charac way to the neuromuscular junction but ends approximately 1.5
teristically there is more epineurial tissue where nerves cross a flm from it. This is a possible entry into the perinerium for for
joint. 319 At any portion of the nerve, the amount of epineurial tissue eign substances such as bacteria or toxins. 172.283 Because of the
is inversely proportional to the number of funiculi. subperineurial space, there is believed to be some movement pos
Observing a peripheral nerve in its tissue bed reveals that it sible for the contained nerve fibers. Funiculi range from 0.04 to
appears to be somewhat convoluted. This appearance is due to 2.0 mm in diameter and the perineurium can range in thickness
the elastin contained within the epineurial tissue. When the limb from 1.3 to 100 flm. In addition to the nerve as a whole appearing
is positioned such that there is little tension on the nerve with somewhat tortuous, the funiculi also have a similar appearance
respect to joint crossings, the nerve takes on the above noted within the epineurial tissue due to the perineurium's elasticity.
Funicular arrangements in peripheral nerves are particularly
interesting. Individual funiculi repeatedly merge and separate
from their neighbors contained within the epineurium, thus
forming funicular plexi (Fig, 5_7).317.321 This results in consider
able variation of funiculi over very short distances. It is esti
mated that the longest portion of nerve with a constant pattern
of funiculi is about 15 mm, but the more typical pattern is a
change every few millimeters. At joint crossings, funiculi are
particularly small and abundant compared to other regions of
the peripheral nerve.
The perineurium serves the functions of protection and main
taining intrafunicular pressure, As previously stated, the per
ineurium is a rather dense connective tissue layer with some
elasticity as well as tensile strength. At regions of joint cross
ings the increased number of funiculi combined with an in
creased amount of epineurial tissue affords some protection
from joint movement and repeated trauma. It is also believed
that the inner mesothelial layer is a good diffusion barrier pre
venting the entrance of foreign substances. 186,238,301,303 The per
ineurium also forms an efficient barrier to the spread of
infection into the funiculi. The circumferential perineurial
layers maintain a certain level of intrafunicular pressure. This is
confirmed by an immediate herniation of the individual nerve
fibers contained within a funiculus when the perineurium is
Figure 5-7. Funicular plexus. A 3-cm segment from the musculocu breached. 306,318 The exact role this pressure plays in the func
taneous nerve of the arm demonstrating the funicular plexus formation. tioning of the axon is unclear but is believed to aid in the normal
Note how transverse section at short distances results in a different axoplasmic flow.
axonal arrangement. (From Sunderland S: Nerves and Nerve Injuries, Endoneurium. Contained within the funiculus and envest
2nd ed. Edinburgh, Churchill Livingstone. 1978. with permission.) ing the individual nerve fibers is a connective tissue known as
Chapter 5 NERVE CONDUCTION STUDIES - 167
the endoneurium (Fig. 5-6). The endoneurium fonns a fine sup was a result of the elevated electrical insulation properties of the
porting sheath about each nerve fiber and at times subdivides myelin. 209•309 He suggested that the action potential would be
the funiculi into small groups of nerve fibers by way of connec generated at the nodes of Ranvier and "skip" over the myeli
tive tissue septae.324 In addition to the connective tissue, the en nated internode regions and introduced the tenn "saltatory"
doneurial tissue contains only capillaries and some localizations with respect to action potential propagation. Approximately 25
of interstitial fluid. The endoneurium is composed of fibroblasts years elapsed before Huxley and Stampfli provided conclusive
and collagen arranged both longitudinally and obliquely. The electrophysiologic evidence of saltatory conduction in myeli
axon, Schwann cells, and associated myelin are surrounded by nated peripheral nerve fibers.149.15o Longitudinal current mea
the endoneurial tissue in a densely packed arrangement fonning surements along the excited axon's surface membrane revealed
a supporting structure referred to as the endoneurial tube. that at each node of Ranvier, the current shifted to a slightly
There is some speculation that the collagen comprising the en later time while it was constant for the entire extent of the in
doneurium is secreted not by the fibroblasts but by the Schwann ternode (Fig. 5-8). Transverse current measurements over the
cells because of the relative paucity of fibroblasts, i.e., there are same nerve demonstrated that a current entered the axon only at
9 times as many Schwann cells as fibroblasts.1· 38.328 A fine retic the nodes of Ranvier and minimal, if any, current passed
ulum of material forming a tubular sheath is located between through the heavily myelinated internodes. This e]ectrophysio
the endoneurium and the basement membrane external to the logic evidence required approximately 30 years for anatomic
Schwann cell cytoplasm known as neurilemma, Schwann evidence to provide insight regarding the actual transaxonal
sheath, or Schwann membrane. 94•324 One may also simply think pathways for ion movement.
of the endoneurium as consisting of two layers, an inner reticu One would anticipate that transaxonal current movement
lar sheath and an outer collagenous sheath. preferentially localized to the nodes of Ranvier should reveal
Individual nerve fibers located within the endoneural sheaths high densities of sodium ion channels. Indirect gating current
display undulations as do the funiculi. A small amount of stretch measurements suggest that mammalian (rabbit) myelinated pe
is therefore possible until the undulations disappear with in ripheral nerves contain approximately 82,000 sodium channels
creasing tension. Although the endoneurium has a limited per node or about 1500lllm2 of the nodal region in order to sus
amount of tensile strength, the majority of stretch is resisted by tain the observed action potentials. 45.46 In rat sciatic nerve this
the epineurium and perineurium. This is exemplified when number is on the order of 21,000 sodium channels per node
nerve roots, which lack a perineurium, fail under tensile forces while frog myelinated nodal membranes contain sodium chan
prior to peripheral nerve rupture.322.324 The endoneurium is not a nels approximating 5,OOOlllm2. 243.245 Similar electrical studies
rigid structure but confonns to its contents. Recall that there is a also suggest that the internodal density of sodium channels is
certain amount of pressure contained within the endoneurium less than 25/j.lm2 P3.274 Morphometric analysis through freeze
that helps to maintain its tubular appearance. If the axon under fracture methods demonstrated a maximum of 3,OOOlllm2 ap
goes degeneration, the endoneurium shrinks but again expands propriately sized particles in the paranodal region and
upon axonal regrowth.320 The endoneurial sheath is also be 2,OOOlllm2 particles in the nodal region that were assumed to be
lieved to serve the function of insulating neighboring nerves sodium channels.13·14.86.356 Potassium channels are sparse in the
from each other with respect to their electrical properties thus nodal region but are present in the internodal and paranodal
avoiding cross-talk or epbaptic conduction.91.llo region covered by the myelin sheath (Fig. 5-9).352.353 Electron
microscopy combined with cytochemical identification tech
Action Potential Generation
niques reveal preferential concentrations of sodium ions in the
Correlation Between Anatomy and Physiology tenninal loops of the myelin lamellae within the paranodal
In 1925, Lillie first proposed that the 10 times greater con region.86 These tenninal loops appear to serve as a reservoir for
duction of myelinated compared to unmyelinated nerve fibers the sodium ions required for nodal depolarization. Additionally,
10
----"-
-----
----'\....--
,
of a myelinated axon. The series of three measure --'
ments from each internode is essentially the same
but demonstrates a noticeable prolongation of la --'\r--
~. ,
tency fonowing each node of Ranvier. B. Recordings
demonstrating that significant current flow associ
-,
''''0''_ sl.
ated with an action potential occurs at the nodes of
Ranvier while the internode is a passive cable con
ductor, thus supporting the concept of saltatory con
•• 1
1
0
--v---
--"'"'"
______ I
• l'
f
duction. (From Stampfli R: Overview of studies on I..
I
....
the physiology of conduction in myelinated nerve
fibers. In Waxman SG, Ritchie JM (eds): Demyelinating
Diseases: Basic and Clinical Electrophysiology. New
York, Raven Press, 1981,pp I 1-23, with permission.)
--
-r--
----"-
\r
.A B
0 OS H) H 2<1 H
168 - PART II BASlCANDADVANCEDTECHNIQUES
Figure 5-10. Cyclic flow of sodium Ions during an action potential. During action potential production at the node of Ranvier, the
sodium ions contained in the junctional cleft between the axolemma and terminal loops (PN: paranodalloops) enter into the axon constituting
the inward current flow when the voltage-dependent sodium gates are opened. Following sodium inactivation, the sodium is actively transported
to the exterior of the axon through the sodium-potassium pump. The extruded sodium is then reabsorbed by the Schwann cell's increased surface
area through the microvilli (MV) and again concentrated in the junctional clefts and terminal loops that act as sodium ion reservoirs. (From
Ellisman MH: Molecular specializations of the axon membrane at nodes of Ranvier are not dependent upon myelination. J Neurocytol
1979;8:719-735, with permission.)
Chapter 5 NERVE CONDUCTION STUDIES - 169
myelinated nerves. 15 ,118,187,190 This is also consistent with what is velocity is shown to be 6 miS/lim for relatively large-diameter
presently known about mammalian myelinated nerves. There myelinated mammalian nerve fibers.148 For example, a nerve
are primarily two major groups of potassium channels, one with fiber with a diameter of approximately 8 lim would be predicted
fast gating kinetics (Kt) and a second group with slow gating ki to have a conduction velocity approaching 48 m/s. Different
netics (Ks; Fig. 5-9). The slow-gated potassium channels are lo conversion factors have been found for nerve fibers with smaller
cated primarily but not exclusively in the node of Ranvier diameters, e.g., 1.7 mlS/J.U11 for unmyelinated nerve fibers. 110,1 19
region, while the fast-gated channels are situated in the paran The above noted designation of nerve fibers by Greek letters
odal region under the myelin sheath. The slow-gated potassium has now been generally accepted as a means to classify nerves
channels most likely contribute in part to the resting membrane based on their size and associated conduction velocity. The clas
potential. However, neither channel type participate in the for sification is as follows: A-a fibers are myelinated fibers with an
mation of the propagated action potential since blocking either approximate external diameter of 6-12 lim, while A-o fibers
type does not alter the action potential's morphology. The im have diameters of about 2-6 lim. The fibers that are unmyeli
portance of the fast-gated potassium channels is primarily to nated and have external diameters of 0,5-2 lim are the C fibers.
prevent bursting or repetitive firing of the axon following action A second classification system considering only afferent fibers
potential propagation past a node of Ranvier. 351 -353 There may was introduced by Lloyd, in which Roman numerals are used. 2lO
be several subtypes of fast-gated potassium channels but their This system's classification is based on fiber diameter and its
explicit roles in action potential burst suppresion remain to be relation to the Greek letter classification is designated: 1(21-12
fully elucidated. In myelinated fibers, voltage clamp experi lim); II (12--6 lim: A-a.); III (6-1 lim: A-o); and IV « 1 lim: C
ments document that repolarization is not conveyed by a potas fibers).
sium current but occurs through sodium inactivation and a
sodium or potassium back-leak current mediated through non Fiber Diameter and Velocity Correlates
voltage-gated or passive ion channels. 25 ,44,136 Intra-axonal inves In order to compare the relationship between fiber diameters
tigations have supported these observations. 188,189 and various aspects of the compound nerve action potential in
living healthy humans. it is possible to remove 2-5 fascicles
Compound Nerve Action Potential 10-15 cm in length from the sural nerve. Microscopic analysis
Fiber Diameter and Conduction Velocity of this small portion of the nerve results in a histogram display
If a maximal depolarizing stimulus applied to a mixed periph ing the range of myelinated fiber diameters contained within the
eral nerve and the ensuing resultant action potential is recorded sural nerve (Fig. 5-1 I). For fiber diameters between 2 and 12
several centimeters distal to the activation site. a characteristic jlm, there is a bimodal distribution with respect to size and cor
spike potential is recorded. When this experiment is performed, responding numbers of nerves. 198 One group of nerve fibers
it is noted that as the distance between the stimulus and record ranges from 4 to 12 jlm, while the second major subgroup lies
ing sites increases, the observed nerve action potential changes between 2 and 4 lim. A third large category of nerve fiber diam
from a single spike into a temporally dispersed potential with eters range from approximately 0.25 to 1.5 lim. Individual nerve
several peaks separated in time (Fig. 5- 11).90,107,198 These investi fibers 11-12 jlm in diameter comprise the largest fibers exam
gations clearly demonstrate that the recorded action potential ined in any quantity.
arising from a mixed peripheral nerve is composed of multiple Recording the compound nerve action potential from the
subcomponent action potentials likely correlated to individual above nerves results in the anticipated three-peak potential. The
nerve fibers each with their own and slightly different conduc three peaks correspond to the A-a.. A-B, and C subcomponents.
tion velocities, thus yielding a compound nerve action poten By knowing the distance between the stimulation and recording
tial. The original studies were performed on frog sciatic nerves points as well as the arrival times for various waveform portions
and produced a prominent waveform designated the "A poten to the site of recording, it is relatively simple to calculate a con
tial," which consists of several subcomponent peaks referred to duction velocity for the identified subcomponents. For example,
in increasing times of arrival (decreasing conduction velocity) if the distance between the site of stimulation and recording is
by the Greek letters a., ~, 'Y, and O. In other words. the fastest 100 mm and the time it takes the leading portion of the action
conducting fibers (a. fibers) arrive at the recording site first while potential to cover this distance is 10 ms, the nerve conduction
the slowest-conducting nerves (0 fibers) are recorded later. The velocity is 10 mls (NCV = distance/time; NCV = 100 mmll0
A-a. and A-~ peaks of the compound nerve action potential ap = =
ms 10 mmlms 10 mls). In the teased sural nerve fibers, the
parently are one and the same as different investigators labeled beginning of the A -a. peak was determined to be 61 mls. The A
the same peaks differently.198 Additionally, the 'Y peak was later B peak had a conduction velocity of 19 mis, while the fastest C
shown to be a recording artifact. As a resul~ there are only two fibers propagated at 1.6 mlS.198 Because we know that the
peaks now designated in the A potential, i.e., A-a. and A-o. A fastest-conducting nerve fibers are the largest-diameter fibers.
second major peak designated the "B potential" is believed to we can align the histogram from largest to smallest and com
consist of slower-conducting fibers than those in the A potential pare the fiber diameters with the compound nerve action poten
and are found only in preganglionic autonomic fibers, which are tial's various peaks. For example, the fibers propagating at 61
small-diameter myelinated nerves. Finally, there is another class mls are the 11- and 12-lim diameter fibers. This yields a nerve
of even slower-conducting fibers known to comprise a third conduction velocity to diameter ratio of 5.3:1, which is in close
major compound nerve action potential peak and referred to as agreement with the 6.0: 1 ratio previously noted. Similar corre
the "C potential." The C potential is generated from small un lations can be drawn for other fiber diameters and velocities. In
myelinated nerve fibers that consist of sympathetic and afferent addition to examining teased fascicles in vitro, corresponding
dorsal root fibers. 198 clinical studies have also been performed in vivo on healthy
The fibers producing the A potential demonstrate a linear re sural nerves with near-nerve recording and stimulating tech
lationship between conduction velocity and external fiber diam niques. I 96-198 Findings for whole nerve are similar to those for
eter. This relationship between fiber diameter and conduction teased preparations.
170 - PART II BASIC AND ADVANCED TECHNIQUES
p,v
100
I
A
It:
~. ~4
I.tJ
0
~ It:
~
54
....
0
e ~2
:Il
"'...... :2
-
0
0
4 8 /2 I. 0 0.5 1.0 1.5 2.0
DIAMETER (pm) DIAMETER {pm)
B
~4
o
o
I.
L....."""-........_ _ _-'=1A.LJ.J.J...U-Uo..I..L.U~
12 8
DIAMETER (pm)
4
oL-__~~fiW~~~~~~~
2.0 1.5 1.0
DIAMETER (pm'
0.5 0
Figure 5-11. Compound action potential and histograms of fiber diameters of normal nerve. Myelinated fibers are represented on the
left. unmyelinated fibers on the right. (From Lambert EH, Dyck PJ: Compound action potentials of sural nerve in vitro in peripheral neuropathy. In
Dyck PJ,Thomas PI(, Lambert EH, Bunge R (eds): Peripheral Neuropathy. 2nd ed. Philadelphia.W.B. Saunders, 1984, pp 1030-1034, with permission).
Biopsy specimens from normal humans reveal that the sural nerve action potential's major spike recorded at the mid-calf is
nerve contains approximately 6600 fibers.32 About 2600 fibers about 14 J!V and is estimated to arise from 1800 large nerve
are in the 7-131J.1Il range, while roughly 4000 fibers have diam fibers. The slower components of the recorded potential (spike
eters ranging from less than 1.0 J!m to 7 J!m. Stimulating the components following the main spike) and are believed to arise
sural nerve maximally (enough current to activate all of the from fibers 7 J!m in diameter or less. At the mid-calf, the slow
fibers) and recording at two proximal sites (e.g., mid-calf, 15 est velocities averaged 15 mis, which corresponds to fibers 4
cm and popliteal fossa 50 cm) reveals a number of interesting 11m in diameter. Recording in the popliteal fossa for the same
findings (Fig. 5-12). The peak-to-peak amplitude of the compound sural nerve revealed that the amplitude of the major spike had
Chapter 5 NERVE CONDUCTION STUDIES - 171
I I
O~--r---r-~~~~U
20 18 16 14 12 10 8 6 4 2 o o 1.0 2.0 3.0
DIAMETER ( pI TIME (msl
Figure 5-13. Compound nerve action potential modeling. A series of triangles were correlated to the fiber diameter distribution of a cat
saphenous nerve and subsequently summated to yield a predicted action potential. The correlation between the predicted potential and. that actu
ally recorded agree amazingly well.The only difference is noted by the dotted line. (From Gasser HS, Grundfest H:Axon diameters in relation to the
spike dimensions and the conduction velocity in mammalian A fibers.Am J Physiol 1939; 127:393-414, with permission.)
172 - PART II BASIC AND ADVANCED TECHNIQUES
populations with respect to anticipating the effect on conduction wise to take a lesson from our surgeon colleagues regarding pa
velocity. Subsequently, more elegant and sophisticated tech tient positioning. Three principles should guide the practitioner:
niques have confirmed this deceptively simple method of sum (I) patient comfort, (2) examiner comfort, and (3) anatomic ex
mating triangles. Of note, essentially the same method is posure. As noted previously, the patient must be comfortable
employed in present-day highly sophisticated computer model with the practitioner, surroundings, explanation of procedure,
ing techniques. and physically able to relax. Patient comfort and relaxation
ensure an optimal examination. In order to collect the necessary
data, the practitioner must be comfortable. Many studies can be
BASIC NERVE CONDUCTION STUDY (NCS) quite time-consuming and the uncomfortable practitioner has a
PRINCIPLES tendency to rush the examination thus potentiating improper
data collection or an incomplete consultation. Finally, the
A nerve conduction study may be defined as the induction region of the body to be examined should be readily accessible
of a propagating action potential in the peripheral nervous to the stimulating electrodes and measurements required.
system and the subsequent recording of its neural impulse at Attempting to stimulate a nerve or measure distance in an awk
some location distant to the impulse's initiation site. One may ward position only predisposes one to experimental error (see
investigate a number of different types of nerve conduction below). Of course, proper exposure should not cause the patient
studies such as: pure motor nerve evaluations by assessing the any undue discomfort.
evoked compound muscle action potentials (CMAPs), pure Before beginning neural excitation, the patient must be
sensory nerve action potentials (SNAPs), and compound warned that an electrical impulse is about to be delivered. Many
nerve action potentials (CNAPs) from mixed (motor and sen individuals are uncomfortable with electricity and afraid of
sory) nerves. By calculating the ability of peripheral nerves to being shocked. The patient should be told what to expect when
conduct an electrical impulse, it is possible to assess their the current is delivered. Some statement such as "a tingling sen
functional status in a healthy state and responses to various sation will be felt down your hand and into your fingers (de
disease processes. Nerve conduction studies allow one to ac scribe which fingers) and your muscles might jump" should be
curately localize focal lesions or detect generalized disease given to the patient. Also, it is a good idea to begin at a zero cur
processes along accessible portions of the peripheral nervous rent intensity and slowly approach the desired intensity allow
system. By first considering the general principles pertinent ing the patient to become familiar with the electrical sensation.
to performing nerve conduction studies, we can better appre Indirect lighting may also be of help. A patient in the supine po
ciate the various factors affecting our ability to perform opti sition stares at the ceiling by default and possibly into bright
mal investigations. overhead fluorescent lights. This can be disconcerting and
simply annoying, especially if the examination begins to ap
PATIENT CONSIDERATION proach 1 hour. Considerations given to the patient as those
noted above will ultimately result in a fruitful electrodiagnostic
The practitioner must first direct attention to the patient. medicine consultation for both the patient and physician.
Placing the patient in the supine position on a comfortable
plinth allows one to examine significant portions of the periph STIMULATION
eral nervous system while at the same time affording the patient
an opportunity to maximally relax. Relaxation is of prime im For the purposes of NCS, the peripheral nervous system may
portance in optimizing the electrodiagnostic medicine examina be activated in one of two ways: (1) electrical stimulation or (2)
tion. Because the majority of electrophysiologic responses are magnetic stimulation. In this chapter magnetic stimulation is
small and significant amplification is necessary, any noise aris not covered as its full diagnostic potential with respect to pe
ing from anxiety-induced muscle contraction may well obscure ripheral nerve disease remains to be explored in more detail (see
the desired response. Patient cooperation and relaxation can chapter 10 on Magnetic Stimulation). In short, magnetic stimu
most easily be obtained by completely explaining the procedure lation cannot fully depolarize the full complement of fibers con
about to be performed in simple and understandable language. tained within a peripheral nerve.92 This technical shortcoming
A number of patients often arrive at the examiner's office misin leads to rather obvious limitations in its diagnostic usefulness.
formed by well-intentioned acquaintances or physicians with At this time the greatest utility of magnetic stimulation appears
respect to the procedures performed and the amount of discom to be limited to excitation of the cerebral cortex and possibly the
fort experienced. A full explanation of the procedure, purpose spinal cord. When referring to stimulation in this chapter, there
and importance of the examination, as well as the sensation fore, it is assumed that electrical and not magnetic excitation is
about to be experienced is important to convey. This can only be employed.
carried out with credibility if the practitioner has experienced Electrical depolarization of the peripheral nervous system
electrical excitation of the peripheral nervous system firsthand. can be accomplished by using either surface or needle elec
All practitioners, therefore, should have nerve conduction stud trodes and delivering a square wave pulse. The more commonly
ies performed on themselves prior to subjecting patients to these used type of stimulation uses a surface cathode and anode. The
procedures. After the patient has been informed as to the benign cathode or negative pole of the stimulator results in a localized
nature of the nerve conduction study and why it is important to region of negative potential while the anode produces a sur
obtain the desired information, they are usually able to cooper rounding region of excess positive potential. Current flows be
ate fully with the practitioner. tween the anode and cathode with decreasing density as
Once the electrodes have been attached to the patient (see distance from the poles increases (see Chapter 3). Should these
below) and before a nerve is excited, the limb must be properly two poles be located over excitable tissue such as peripheral
positioned. Positioning is one of the most important aspects of nerve, a region of depolarization is induced about the nerve
the nerve conduction examination. The practitioner would be under the cathode. If the cathode produces a depolarizing impulse
Chapter 5 NERVE CONDUCTION STUDIES - 173
of sufficient magnitude to exceed the transmembrane voltage intense stimulus deliveries (elevated current/voltage and/or
threshold for sodium activation, then a self-propagating action pulse duration) may be necessary in nerves difficult to excite
potential is generated. The action potential generated under the secondary to the previously noted conditions or disease states.
cathode will propagate both proximally and distally from the In these situations, consideration should be given to the amount
cathode along the nerve's longitudinal course. Those action po of stimulation required. As the current is gradually increased
tentials traveling toward the anode may be partially extin from a threshold to maximal intensity, the larger myelinated
guished at the hyperpolarized region surrounding the anode axons are activated preferentially because of their lower thresh
(anodal block) or collide with action potentials produced under 0Id.60·61.354 With supramaximal stimuli, the remainder of the rel
the anode (anodal break excitation).I40 The occurrence of atively smaller myelinated axons are excited. Also, the larger
anodal block in routine conduction studies is questionable as fibers may be preferentially activated by using submaximal cur
one can typically detect a similar response by reversing the lo rent intensities with relatively long pulse durations of 500 or
cation of the anode and cathode with the expected delay from a 1000 IlS •257.258
more distant excitation site (see Chapter 3). Anodal break exci When stimulating the peripheral nervous system, the pulse du
tation, however, is capable of producing an action potential ration should initially be set between 0.1-0.2 ms and a starting
through neural depolarization at the cessation or "break" of the current intensity of zero delivered. It is also important not to
stimulus. This process has been postulated to occur by imped change the pulse duration between different sites of neural acti
ing sodium inactivation for the duration of the hyperpolarizing vation. A gradual elevation of the current delivered allows the
pulse. 140 As a result there is an inward current flow into the patient to adjust to the stimulating pulse. The evoked response is
membrane attempting to depolarize it. Because of the anodal carefully observed to ensure that it no longer increases in magni
current, however, the nerve is prevented from generating an tude despite an increase in the current intensity. Should the re
action potential. Once the stimulus pulse is over, the sodium in sponse's amplitude continue to increase despite reaching the
activation persists long enough to result in an action potential, highest intensity on the stimulator, a longer pulse duration can
i.e., anodal break excitation. It is this action potential that may be used. The pulse duration is increased to the next highest set
collide with the one originating under the cathode. No doubt, an ting and the current intensity is again reset to zero. The above
action potential propagates away from both the cathode and process continues until a supramaximal waveform is docu
anode. mented. The frequency of stimulation is usually set to I Hz.
In addition to surface electrodes, needle electrodes may also Some practitioners prefer to stimulate not with a fixed stimulus
be used to evoke an action potential. Needle electrodes are usu frequency but by applying every stimulus manually using the
ally used when the nerve is hard to stimulate with surface elec foots witch on the EMG machine. Basically, it is important not to
trodes, although some investigators use needles routinely. If a deliver more stimuli to the patient than necessary. This implies
nerve is surrounded by excess subcutaneous tissue or edema that the investigator should have time between every stimulus to
preventing optimal stimulation with surface electrodes, a needle judge the respons and make changes with regard to stimulus pa
cathode in combination with a needle or surface anode may be rameters. Stimulus rates higher than 1 Hz are generally unneces
required. The advantage of needle stimulation is a more precise sary except with the purpose of averaging the response.
localization of the depolarizing pulse with less current/voltage If any difficulty is noted in obtaining the anticipated re
required. 28 Less current/voltage can also mean less discomfort. sponse, several procedures should be explored prior to condud·
Of course, there is a small risk of trauma to the nerve with ing that the response is absent. First, as noted above, a
needle stimulation secondary to accidental neural insertion. A supramaximal stimulus must be assured. If the current intensity
pulse duration of 50 J.ls usually suffices for needle stimulation. is maximal and a pulse duration of 0.5 ms or more is attained,
For a more detailed discussion of needle stimulation refer to one can be assured that a suprarnaximal stimulus has been de
Chapters 2 and 3. livered. The question then arises as to whether the stimulus was
The magnitude of the stimulus can be categorized qualita delivered to the nerve under investigation. Of course, one
tively in number of ways. A stimulus pulse with an intensity just should not attempt to perform an electrodiagnostic examination
capable of evoking an observable response is referred to as a without first being thoroughly familiar with peripheral nerve
threshold stimulus. I Stimulus intensities less than the thresh and muscle anatomy. Moving the cathode several centimeters
old level are called subthreshold stlmuH. Maximal stimuli are from side-to-side ensures covering the nerve's anticipated loca
those that do not produce any further increase in the response. tion. All electrode leads must be checked for continuity as the
Those stimuli at intensities between threshold and maximal stimulus may not be reaching the patient or the response may
levels are known as submaximal stimuli. Finally, a stimulus not be arriving at the instrument. Although obvious, it is always
delivered at approximately 20-33% above the maximal inten a good idea to verify that the amplifier/preamplifier is on.
sity is called a supramaximal stimulus. It is the supramaximal Finally, averaging the response several times may improve the
stimulus that is the preferred intensity to be delivered in the ma signal-to-noise ratio sufficiently to resolve a small response ob
jority of routine nerve conduction studies. One can also easily scured by baseline noise (see Chapter 3). The especially deter
quantify the stimulus used in peripheral nerve studies. An in mined practitioner may consider recording from the nerve or
strumentation parameter defining the duration during which a muscle under investigation with a needle electrode to maximize
stimulus is delivered is known as the pulse width or pulse du the response's amplitude. Should all of these measures fail to
ration and is measured in milliseconds or microseconds. A typ produce a response, it is most likely absent secondary to pathol
ical pulse duration for most nerve conduction studies is 100 J.ls ogy and not because of a technical deficiency.
or OJ ms with a range of 50-1000 J.ls. Once the practitioner has
chosen the appropriate pulse duration, greater for nerves deep RECORDING
below the skin surface, the intensity or amount of current/volt
age delivered is adjusted to a supramaximal level. Typical volt Following action potential generation it is necessary to record
age levels are between 100 and 300 volts or 5-35 rnA. More the induced response. As with stimulation, one may use either
174 - PART II BASIC AND ADVANCED TECHNIQUES
surface or needle electrodes. The optimal type of electrode de about the needle electrode now includes the slow conduction of
pends on the situation (see Chapter 3). Surface electrodes in muscle fibers (4-6 m/s) and varies from one site to another.
general are somewhat more convenient to use because they can Instead of the one latency reflecting depolarization of the end
be taped over the appropriate location and easily repositioned to plate zone, a needle located at some location in the muscle de
another location. Additionally, because the skin's protective bar pends upon slow conduction along the muscle fibers prior to
rier is not penetrated (except for somatosensory evoked poten reaching the particular location of the needle. Intramuscular
tials, see Chapter 9), there is less patient discomfort and less of needle placement, particularly a concentric needle, does have
a concern regarding blood-borne infectious agents. As their the advantage of selectively recording from a small area. This
name implies, surface electrodes are located on the body's sur can be used to one's advantage in order to avoid volume-con
face, and as a result are relatively far from the activated neural ducted responses from neighboring muscles (see Chapter 2).
or muscular tissue. This "distant" location has the advantage of When recording a response from nerve or muscle, three elec
recording the summated response from a large portion of the de trodes are required to obtain a response: active, reference, and
polarized tissue. This detected response is more representative ground electrode. The active electrode is placed as close to
of all of the tissue's fibers undergoing depolarization. As a the tissue under investigation as possible. This electrode is con
result, surface electrodes are more appropriate when the total nected to the noninverting amplifier port (see Chapter 3) and
amount of depolarization is important, thereby attempting to may be referred to by several terms in addition to active elec
quantify what portion ofaxons or muscle fibers were activated. trode. Initially the active electrode was caned G1, which arose
Needle recording electrodes, although used less frequently, from the physiology and electroencephalography literature des
also have some advantages in particular circumstances despite ignating the active electrode as Grid 1. More recently, the term
the small amount of discomfort and possible patient anxiety as Gl is also called E-1 for electrode 1 because the designation
sociated with their use. When there is excess swelling about a "active" becomes inadequate to accurately describe the situa
muscle or nerve and inadequate surface recordings are obtained, tion encountered in far-field recordings (see Chapter 2). Also,
a needle electrode may be capable of better delineating the pres this electrode may occasionally be designated the noninverting
ence or absence of a response. The advantage of a needle elec lead. The second or reference electrode is plugged into the in
trode is that it can be located next to, or within the tissue under verting amplifier port and was previously known as G2 repre
investigation and record action potentials in nerve or muscle senting the Grid 2 electrode. As with E-I, the reference
with only a few active fibers. It is possible, therefore, to docu electrode is designated E-2 or the inverting lead. This electrode
ment the presence of surviving axons or muscle fibers when sur is usually placed at some distance from the active electrode so
face recordings may detect no response. This same capability, that the information from E-I is "referenced" or compared to E
however, may also be a limitation when recording within nerve 2. Through the process of differential amplification, the ob
or muscle. Placing a needle next to the nerve may produce a rel served potential on the cathode ray tube (CRT) is really the
atively large amplitude even if surface recordings yield a small difference in voltage between the two electrodes, i.e., (E-I)
response, but slight needle movement can produce large shifts (E-2). The actual locations of these two electrodes designate
in the amplitude. Positioning the needle in the same location be whether the recording is a bipolar or referential montage (see
tween examinations to give identical amplitude readings is Chapter 2).
somewhat challenging and requires significant skill to ensure The anticipated site of E-l and E-2 placement should be
reproducibility. Surface electrodes yield more reproducible re properly prepared with fine sand paper or a commercial pumice
sults despite smaller amplitude recordings because the previ solution in order to reduce the skin's impedance if difficulty
ously noted distance effects on amplitude are comparatively with interference is encountered. Reducing skin impedance
reduced. Serial studies, particularly regarding blocked fibers, ensures that the electrical activity generated within the body is
may be difficult to perform with needle recording techniques. 25o actually recorded by the instrument to be amplified and subse
When a needle electrode is used, it must be properly sterilized quently displayed. Skin preparation is of particular importance
or discarded. when recording sensory or mixed nerve potentials because of
If a needle is located relatively close to a nerve, the observed their particularly small size. A commercial electrode paste or
response adequately reflects the number ofaxons excited (given gel is then placed on the anticipated site of electrode placement
the above noted limitations) because it records the summated to assist in the electrodelskin electrochemical coupling, thus op
response within the volume conductor. This principle is also timizing the response's presentation to the instrument.
true for recording the induced depolarization in a muscle pro
vided the needle electrode is located subcutaneously superior to MOTOR NERVE CONDUCTION STUDIES
the fascia overlying the muscle belly. Placing a needle electrode
within the activated muscle, however, does not result in re Using the above principles of peripheral nervous system stim
sponses that accurately reflect the summated electrical activity ulation and recording, it is possible to assess only the motor
arising from total muscle depolarization.147.225 This is because fibers contained within a peripheral nerve. Recall that there are
the depolarized tissue surrounding the needle's small active sur no pure motor nerves accessible to the nerve conduction tech
face preferentially contributes to the amplitude of the recorded niques. Every nerve innervating a muscle not only contains
potential while at the same time acting as a low-pass filter to motor efferents to that muscle, but also multiple sensory or affer
reduce the high-frequency spike contribution from more distant ent nerves conveying data from the muscle spindles and Golgi
muscle fibers. The subcutaneous needle, especially with a large tendon organs as well as autonomic fibers. Given this stipulation,
surface area exposed, however, is different because it is located we can nevertheless evaluate the action potential characteristics
superior to the muscle but within the body's volume conductor of the motor fibers innervating a particular skeletal muscle pro
and summates the response from the muscle similar to the sur vided recording electrodes can be placed on or in the muscle.
face electrode. Also, the onset latency can change with different The technique of performing a motor study on any peripheral
locations within the muscle because the time to depolarization nerve first begins with the proper location of recording electrodes.
Chapter 5 NERVE CONDUCTION STUDIES - 175
~5mv
demonstrates an initial upward or negative deflection in re
sponse to neural excitation and subsequent depolarization of the
entire muscle. For discussion purposes, we assume a supramax
5ms imal stimulation for all responses thereby assuring complete
neural activation for the muscle under investigation. The initial
Figure 5-15. Ulnar nerve CHAP to FDI. A, An E-I electrode is
baseline departure for the CMAP, onset latency, is negative be
located over the first dorsal interosseous' mid-belly with an E-2 elec
cause we have purposefully positioned the E-! recording elec
trode secured to the second metacarpophalangeal joint. The CMAP
trode over the muscle's endplate region (Fig. 5-16). Upon
begins with an initial positive deflection. B, Repositioning the E-2 elec
muscle depolarization, the current is directed inward at the site
trode to the first metacarpophalangeal joint results in a CMAP with an
of action potential initiation, the motor point, thus constituting a
initial negative deflection. C,An E-I is located on the radial styloid with
negative current flow. The voltage associated with the negative
an E-2 electrode positioned on the second metacarpophalangeal joint.
current is what is measured by the E-l electrode and is reflected
Note that a large potential is recorded by these two distant electrodes
as a CRT trace deflection in the negative direction. Because the
suggesting that the waveform is primarily a far-field potential.
instrument initiates the sweep at the start of the cathode's depo
Therefore, the waveform recorded in B derives in part from an FDI
larizing pulse, the CMAP's first baseline departure reflects the
near-field potential and interosseousflumbrical far-field potentials (C).
arrival time at the muscle of the fastest-conducting nerve fibers.
This time is composed of the following: latency of activation
case the muscle's motor point has been missed (Fig. 5-14B); (utilization time), neural conduction, and neuromuscular junc
however, repositioning the reference electrode may improve the tion transmission. Recall that the onset latency is dependent
situation in a few select cases (Fig. 5-15). upon the instrument's amplifier sensitivity (see Chapter 3). The
higher an amplifier's gain, the earlier a departure from the base
Parameters line can be detected. This fact emphasizes the necessity of du
A number of parameters regarding the motor nerve's CMAP plicating individual laboratories' instrument settings prior to
can be measured in an attempt to quantify the response, thus in using their reference data.
creasing its diagnostic utility. Given most instruments' capabili Following neural excitation, a CMAP is detected on the CRT
ties to automatically calculate a number of the waveform's screen. The onset latency is measured by placing the instru
parameters, a substantial amount of data can be gathered in a ment's latency marker on the region of the CMAP identified as
relatively short time. It is important to keep in mind, however, the initial departure from baseline. From the above discussion, it
that the quantification of a waveform's characteristics does not can be appreciated that there are a number of processes that must
necessarily substantiate its clinical utility. We will define a occur prior to the observation of the CMAP. Once the stimulator
number of CMAP parameters that have been shown to have has been activated, there is a certain amount of time required for
clinical relevance or may be of importance in the future. The the transmembrane voltage difference induced by the cathode to
waveform constituents to be discussed are: phase, onset latency, reach the depolarization threshold. The time to peak cathodal
termination latency, nerve conduction velocity, negative wave negativity is minimal as all commercially available instruments
form duration, amplitude, rise time, area, and stability. The clin use a square wave pulse that achieves its peak essentially instan
ical utility of a number of these parameters remains to be fully taneously. Neural propagation can be considered to have been
appreciated and awaits the quantification in both normal sub initiated once threshold is reached and sodium activation begins.
jects and patients with specific disease states. The duration of time between cathodal current initiation and that
Phase. The optimal CMAP morphology is an immediate necessary to achieve sodium activation with ensuing propagation
negative (upward rise from the CRT's baseline) deflection that is referred to as the latency of activation (utilization time) and
rises to a peak with a subsequent return to the baseline. The has a duration of approximately 0.1 ms. Once the neural im
CRT trace then continues below the baseline (positive direction) pulses are initiated, action potentials travel along the peripheral
to form a second peak. A gentle sloping return to the baseline nerve to the muscle's neuromuscular junctions. The time neces
forms the terminal aspect of the CMAP (Fig. 5-16). During the sary to reach the muscle is variable because it is directly depen
course of describing the typical CMAP, the CRT trace describes dent upon the length of nerve between the point of stimulation
a number of phases. We may define a phase as that portion of and the muscle. Upon reaching the neuromuscular junction, the
Chapter S NERVE CONDUCTION STUDIES - 177
complex process of electrochemical induction of an action po Termination Latency. The CMAP's termination latency
tential from nerve to muscle must occur. The time required to is defined as that portion of the waveform where the gradual
achieve neuromuscular transmission and muscle action poten return of the CRT trace intersects the baseline (Fig. 5-16).
tial induction with subsequent CMAP appearance on the CRT is Because the terminal portion of the CMAP's positive phase
approximately 1.0 ms. The onset latency, therefore, is the result slowly returns to the baseline, it is occasionally somewhat diffi
of neural activation at the cathode (latency of activation), action cult to decide this aspect of the waveform. That time period rep
potential conduction along the nerve, and neuromuscular junc resented between the onset and termination latency defines the
tion transmission. potential's total waveform duration.
Occasionally the CMAP does not demonstrate an abrupt neg Nerve Conduction Velocity (NCV). One of the more com
ative deflection but an initial positive deflection describing a monly calculated CMAP parameters is the rate at which a
positive phase of variable amplitude preceding the major nega neural impulse propagates along the motor fibers stimulated,
tive CMAP spike. This finding indicates that the active elec i.e., its nerve conduction velocity. The NCV is calculated by
trode detected an initial positive current source prior to dividing the distance over which an action potential travels by
detecting the negative sink (see Chapter 2). When a positive de the time required to cover this distance, i.e., NCV = D (dis
flection precedes the negative spike, one can assume that the tance)/t (time). Once the NCV for a patient is known, it can be
active electrode is not located on the muscle's motor point, or a compared to a reference database to assess whether pathology
complex interaction between the electrodes detecting both near affects the nerve under study. If the calculated NCV is less than
field and far-field potentials is occurring. Fortunately, this situa normal, one must conclude that the detected slowing is a result
tion can be easily rectified by slightly repositioning the active of demyelinationlremyelination, loss of the fastest-conducting
electrode until a negative deflection is achieved indicating a fibers, or both.
recording location over the motor point, or relocating the refer The accepted manner of determining motor conduction ve
ence electrode. Infrequently, a muscle may be encountered in locities is to stimulate the nerve at two different locations and
which the motor point simply cannot be found because of measure the distance between these stimulation sites. This dis
anatomic distortion due to a normal variation or pathology. In tance is then divided by the interval separating the two stimuli.
this instance, one should measure the onset latency to the initial Convention dictates that it is less desirable to stimulate a nerve
baseline departure in the positive direction. Consistency should in only one location and then calculate the NCV based upon the
be applied by also measuring other responses obtained from this separation between the stimulus and recording site. The ratio
muscle with different stimulation sites to the same initial posi nale in this instance is to remove the uncertainty and variability
tive deflection. of neuromuscular transmission time and latency of activation. If
A second problem may arise from the premotor potential, the NCV is to be calculated with only one stimulation site, the
which is a small sensory potential preceding the CMAP to both latency of activation and neuromuscular transmission time must
median and ulnar nerve stimulation at the wriSt.81.97.197 This po be subtracted from the onset latency, i.e., onset latency minus
tential's amplitude usually does not exceed 50-70 JlV and, 1.1 ms. By stimulating the nerve in two locations and determin
therefore, is not a problem unless high amplifier sensitivities are ing the NCV over this distance, however, the neuromuscular
used. The small negative deflection may result in the appear junction and theoretically that portion of the nerve between the
ance of a slight positive phase preceding the CMAP, thus sug distal stimulation site and the motor point is precluded from in
gesting that the recording electrode is not located on the fluencing the NCV. Because the latency of activation is assumed
muscle's motor point. If numerous attempts at repositioning the to be the same for all portions of the same nerve, it is of no con
E-l electrode fail to result in an initially negative onset, the am sequence in the final NCV determination. Although the above is
plifier sensitivity should be increased to 50 IlV/div in order to generally true, a word of caution must be expressed regarding
more closely inspect the CMAP's onset. If a small negative po the concept of eliminating the portion of the nerve between the
tential is observed, one may conclude that the premotor poten distal stimulating site and the motor point.
tial is present and one then measures to the CMAP's onset As an illustrative example, let us assume that we are record
following the premotor potential. Also, the amplifier sensitivity ing from the motor point of the median innervated thenar mus
may simply be decreased until the response is no longer visible, cles. Our two stimulation sites are just proximal to the distal
thus making CMAP onset measurement much easier. Of course, wrist crease and the antecubital fossa. Suppose a lesion exists at
altering the amplifier's sensitivity may delay the CMAP's onset the wrist just distal to the wrist stimulation site and has resulted
latency, but hopefully this will not extend into the "abnormal" in the loss of nerve fibers capable of conducting at 50
range. If it does, the increased amplifier sensitivity option may meters/second (mls) and greater, but sparing those conducting
be required. One should realize that the descending portion of 49 m/s or less. By stimulating the nerve just proximal to the
the premotor potential's negative peak can interfere with the lesion site and elbow, it is clear that the fastest fibers measur
CMAP's negative onset, thus altering the CMAP's true onset la able are 49 mls even though fibers of 50 mls and faster are com
tency. In this case, consistency is the key and the practitioner pletely intact between the two stimulus sites. Even though the
should decide the most appropriate course of action (see above) 50 mls or faster fibers are stimulated, they do not contribute to
and use this technique on all such responses (see Chapter 2). the CMAP secondary to wrist blockage. One should now recog
Irrespective of the amplifier gain used, the same setting should nize that a lesion not incorporated into the neural segment under
be used for all stimulation sites in order to calculate a valid con investigation can continue to have quite a profound impact upon
duction velocity. the NCV results.
The onset latency is frequently used for diagnostic purposes. The units placed into the NCV equation are important to con
Disease processes starting at the distal expanse of the nervous sider. The conventional manner for reporting an NCV result is in
system can usually be detected because of a prolongation in the the units of meters per second (mls). The electrodiagnostic instru
CMAP's onset latency. So-called "dying back" neuropathies ment reports time intervals in milliseconds (ms) when the onset
may manifest initially as onset latency prolongation. latencies are measured on the CRT. If one records the distance
178 - PART II BASIC AND ADVANCED TECHNIQUES
between stimulation sites in millimeters (mm), it is simple to the waveform's total duration may be increased, i.e., temporally
quickly convert to mls. For example, if the time interval for 200 dispersed.
mm is 5 ms, the NCV is 40 mls (NCV = distance (d)/time (t) = Amplitude. In addition to onset latency and NCV, the
200 mm/5 ms = (40 mmlms) x (l mllOOO mm) x (1000 ms/Is) CMAP's amplitude is one of the more frequently used parame
=40 m/s. As long as the numerator is in millimeters and the de ters in assessing pathology. There are two ways in which to mea
nominator is in milliseconds, the two numbers associated with sure the CMAP's amplitude: baseline-to-peak and peak-to-peak
the units can simply be divided and mls incorporated into the (Fig. 5-16). Baseiine-to-peak amplitudes are calculated by first
NCV. On the other hand, if the distance is in centimeters (cm), a extending an imaginary baseline with that preceding the CMAP
conversion factor is required to convert em to mm, i.e., multiply from the onset latency to an intersection with the falling negative
the result by a factor of 10. portion of the negative spike. The distance between the highest
Negative Waveform/Spike. As previously stated, by con peak of the negative spike and the imaginary baseline immedi
vention, phases comprising the CMAP above the baseline are ately beneath it represents the baseline-to-negative peak ampli
considered to be negative. In CMAP studies there is usually one tude of the CMAP. It is this amplitude that is believed to most
major negative phase, often called the CMAP's negative spike accurately represent the total number ofaxons and their inner
(Fig. 5-16). This portion of the CMAP is an important compo vated muscle fibers depolarized. This is because the negative
nent because it contains several parameters of diagnostic utility. sink contained within the motor point for all muscle fibers depo
The onset latency defines the initiation of the negative spike. larized generates a summated voltage representative of the
That portion of the negative spike opposite the potential's onset number of fibers activated. If fewer fibers are depolarized, a cor
intersecting an imaginary line drawn through the previous iso responding drop in voltage results in a lower CMAP magnitude.
electric line defines the CMAP's negative spike duration. The Peak-to-peak amplitude is calculated by first determining the
duration of the negative spike may become prolonged in dis greatest magnitudes of the major initial negative and subsequent
eases producing differential slowing or temporal dispersion of positive peaks. A horizontal line parallel to the baseline is drawn
the motor fibers' conduction times.181.182 just intersecting each of the tips of the above-noted major peaks.
Duration. The CMAP's duration can be conceptualized as The separation between these two lines signifies the CMAP's
consisting of two separate components. The first or negative peak-to-peak amplitude. Because the major positive peak arises
spike duration has previously been defined as that amount of from the two terminal source currents and propagates away from
time between the CMAP's onset latency and intersection with the electrode as well as consisting of the CMAP's far-field com
the baseline (Fig. 5-16). The second duration of possible inter ponents and possibly those of other muscles, peak-to-peak am
est is the time between CMAP onset and eventual return to plitudes do not yield a good correlation with the number of
baseline of the terminal positive phase. This is the total poten axons/muscle fibers depolarized. Also, the positive portion of the
tial's duration and is rarely considered of diagnostic benefit. In CMAP is where there is comparatively more phase cancellation
some demyelinating diseases with nerve fibers affected differently, of the positive phase of the faster fibers with the negative phase
of slower fibers. Therefore, this region of the CMAP bears less
one-to-one correspondence between amplitude and number of
B fibers depolarized. Practically, however, if good reference data
are available, either technique suffices for routine studies.
One may note that the CMAPs generated by stimulation sites
further removed from the recording site are somewhat reduced
compared to sites closer to the recording electrode. This obser
vation arises because of the temporal dispersion normally pre
sent in motor fibers. There is approximately a 13 mls difference
between the fastest- and slowest-conducting fibers in normal
motor nerves. 72,73 Over increasing distances, the separation be
A tween these population of fibers increases. As a result, the ter
c E minal positive phase of the fastest fibers will increasingly
overlap the negative spike of the slower fibers. Increasing
amounts of phase cancellation produce a potential with a reduc
tion in the baseline-to-peak and peak-to-peak amplitudes. The
minimal increase in temporal dispersion is relatively offset by
o J2000/-'V the naturally long duration of the negative spike of muscle
fibers. The net effect is a mild but noticeable amplitude reduc
2ms tion. In pathologic conditions, it may be possible for the above
noted difference between the fastest and slowest conduction ve
Figure 5-16. Thenar muscle CHAP. Example of a typical CMAP locities to increase, thus resulting in a pathologic reduction in
recorded from the thenar eminence following median nerve excitation CMAP amplitude over a commonly used distance. Also, if there
at the wrist. The time represented by the segment A-B is referred to is greater than approximately 50% reduction in CMAP for a
as the rise time, while A-C is the duration of the negative spike. proximal compared to distal stimulation site, some degree of
Segment A-E represents the duration of the total potential. The ampli conduction block of neural propagation may exist. By incre
tude of A-B is the baseline-to-peak magnitude of the potential, while mentally moving the stimulator, it is sometimes possible to lo
B-D is the peak-to-peak amplitude. The portions of the CMAP be calize the site of conduction block within a few centimeters by
tween A-C and C-E each constitute one phase of this biphasic poten monitoring for the drop in amplitude.
tial. The latency of point A is the onset latency, while point 8 Rise Time. As previously noted, if the active electrode is lo
represents the peak latency. cated directly over a muscle's motor point, the initial departure
Chapter 5 NERVE CONDUCTION STUDIES - 179
from the baseline is in the negative direction. The time required antidromic nerve conduction recording. If the nerve were stimu
for the CRT trace to describe the peak of the CMAP's negative lated at the wrist and a more proximal forearm recording site
spike, peak latency minus onset latency, is referred to as the rise chosen, induced action potentials would be propagating in the
time (Fig. 5-16). In general, the rise time's slope is proportional physiologic direction with respect to the recording electrode.
to the distance between the action potential's source and the This type of recording is called an orthodromic conduction
recording electrode. If the recording electrode is not located on technique. In the previously described motor nerve conduction
the motor point and an initial positive deflection is observed, the studies, stimulating the nerve and recording from a muscle is an
rise time in this instance is from the first positive deflection's orthodromic technique because the motor impulses are traveling
peak to the negative spike's peak. The reversal of potential from toward the muscle as they would physiologically.
positive to negative signifies that the negative current sink has Let us assume we are next going to stimulate the median nerve
reached the E-l recording electrode. sensory fibers in one of the first three digits and record from the
Area. In addition to amplitude, area is an alternative way to mixed median nerve at the wrist. This type of setup constitutes
estimate the number ofaxons/muscle fibers depolarized. The an orthodromic conduction study with a SNAP being recorded
term area as it is commonly used in electrodiagnostic medicine from a mixed nerve. Additionally, the median nerve at the wrist
actually refers to the area under the negative spike of the CMAP. can be stimulated while recording from one of the first three
Commercially available instruments can quite readily calculate digits in the hand (Fig. 5-17). We are now stimulating the mixed
the CMAP's negative spike area. Studies comparing amplitude median nerve at the wrist and recording only from an anatomic
and area for diagnostic purposes with respect to axonal loss and region where sensory fibers originating from the excited nerve
prognosis found comparable results. 361 It is important to recog are distributed. A pure sensory response occurs because only the
nize that the area of CMAPs obtained from both proximal and sensory fibers are located on the digit. In this instance, an an
distal stimulation sites is not equal. 182 This suggests that area is tidromic sensory nerve conduction study is performed.
subject to temporal dispersion effects producing phase cancella Antidromic and orthodromic techniques are equivalent with
tion just as previously described for amplitude. As with ampli respect to onset and peak latency but not amplitude. 30 Although
tude, the area under the positive portion of the CMAP is several studies suggested that the latency differed depending
potentially unreliable in estimating axonal loss when phase can upon the direction of propagation, hand temperature and record
cellation effects are prominent, as in a demyelinating neuropa ing electrode separation were not controlled.47.240.326 A subse
thy causing differential slowing (some fibers altered more than quent study documented that when these factors were
others) of affected fibers.58 controlled, there was no significant difference between these
Stability. In normal nerve and muscle, the recorded CMAP two techniques with respect to latency.49 The amplitude of digi
should maintain the same amplitude and morphology with each tal antidromic responses, when recorded with surface elec
successive stimulation. The constancy of the potential from one trodes, is generally larger than orthodromic potentials because
neural excitation to the next refers to the CMAP's stability. If the recording electrodes are closer to the subcutaneous neural
the nerve is repetitively stimulated at high rates (e.g., 50 Hz), a tissue. In orthodromic studies, the recording electrode is posi
less than 50% increase in amplitude may be noted and is re tioned over a proximally located nerve with respect to the stim
ferred to as pseudofacilitation. 254 The exact mechanism pro ulation site and thus the nerve is typically lying somewhat
ducing this phenomenon is unknown but is postulated to arise deeper in the tissue, which reduces the recorded response. 30
secondary to increased synchronization of motor unit firing. If
sequential peripheral nerve stimulation results in a CMAP B
decrement or amplitude variability, one should suspect faulty
neuromuscular junction transmission or inadequately secured
electrodes combined with movement artifact.
When using needle recordings, however, orthodromic potentials 5-17). Because of the smaller magnitude of the SNAP, an ampli
are comparatively larger than antidromic responses because the fier sensitivity of 10 or 20 f.lVldiv may be required compared to
needle can only be located near a few digital fibers in an the 500 f.lV/div or greater used for CMAPs. This results in more
tidromic studies, while it can be placed close to more fibers at a baseline noise, which at times makes it somewhat difficult to
proximal region in orthodromic investigations. Specifically, accurately determine the waveform's departure from baseline.
placing a ring electrode around a digit excites all nerve fibers Averaging 10-20 responses may remove the baseline artifact
near the ring cathode, which can be recorded with a needle situ and produce an acceptably sharp potential take-off. Historically,
ated next to the nerve at the wrist. Exciting the nerve at the wrist the aforementioned baseline/instrument noise and lack of so
(antidromic technique), however, allows one to place the needle phisticated averagers necessitated measuring SNAPs to the
next to only a few fibers in the subcutaneous tissue of the digit. peak. The peak latency is much easier to define in noisy record
As with all techniques, antidromic and orthodromic sensory ings. As instrumentation improved the ability to record optimal
recordings both have advantages and disadvantages. Antidromic SNAPs even without averaging, onset latency measurement in
sensory responses in the hand are typically larger when using creased in popularity but peak latency remains because of previ
surface electrodes than orthodromic potentials (see above). The ous convention. Of course, the peak latency does not reflect the
disadvantage of the antidromic recording is that it can occasion fastest propagating axon velocities. To some extent, the onset
ally record muscle artifacts, which may interfere with the de also is not a completely accurate descriptor of the fastest veloci
sired sensory potential. This volume-conducted muscle ties since it is an artifact of the recording electrodes and differ
response may originate from the lumbrical muscles as the ring ential amplification. The fastest recording fibers are most
electrodes are located near their insertion. The inexperienced accurately measured to the inflection of the initial positive
practitioner may also mistake the above noted muscle response phase in referential recordings (triphasic SNAP), which signi
for a sensory potential. Muscle artifact is usually not a problem fies the arrival of the negative sink at the E-l recording elec
when using orthodromic techniques as only a sensory nerve is trode. Negative onset and peak latencies are now routinely
excited, thus obviating a concomitant activation of motor measured with standardized techniques. If a triphasic SNAP is
nerves. In antidromic studies, the motor artifact is usually not a detected, the onset latency is defined as the peak of the initial
problem but can be minimized by moving the E-l electrode positive deflection. As long as these techniques are used in
slightly more distal on the digit or having the patient abduct the defining pathology and the various recording artifacts are rec
digits. Also, the motor response is usually delayed with respect ognized, it is acceptable to measure onset and peak latency. This
to the sensory response and its negative peak potential is con is in contrast to a CMAP where one attempts to always record
siderably longer in duration than the sensory response. It is rec from the muscle's motor point and hence generate an initial
ommended that the practitioner become familiar with both types negative deflection.
of techniques and employ them judiciously when appropriate Termination Latency. The termination latency of the
circumstances arise. SNAP is calculated in the same manner as that for CMAPs. As
The basic principles of nerve conduction stimulation and for CMAPs, this parameter is seldom used at the present time
recording are similar for motor and sensory studies. There are a for defining pathologic responses.
few pertinent differences necessary to point out prior to per Nerve Conduction Velocity. Calculating nerve conduction
forming either study in patients. We will review the same as velocities for sensory nerves is slightly different than the tech
pects for the SNAP components as for the CMAP with nique employed for motor nerves. The sensory nerve does not
emphasis on the aspects unique to the sensory nerve conduction contain a neuromuscular junction but the latency of activation is
study. still present. When performing sensory NCVs, either one or two
stimulation sites can be used. If one stimulus site is used, then
Parameters the distance between the stimulus and active recording electrode
Phase. The typical SNAP morphology with a bipolar record is divided by the onset latency minus 0.1 ms (latency of activa
ing montage is biphasic with an initial negative spike followed tion). When two stimulus sites are used, the latency of activa
by a positive spike (Fig. 5-17). In the case of the SNAP there is tion can be ignored as it is common to both. Because a SNAP is
no motor point from which to record and it is reasonable to often recorded from the digits where the nerve fibers are quite
question why it is biphasic and not triphasic. Indeed, one would small, it is important to realize that the distal NCV can be
anticipate that the initial positive source current should be de slower than that calculated for a proximal segment of the same
tected prior to the negative sink, thereby producing an initially nerve. This is because nerve fibers taper as they travel distally
positive triphasic SNAP. However, this is not what is observed and NCV is proportional to the nerve's diameter. This problem
in most digital nerve studies when ring and bar electrodes are is also present for motor fibers, but is less prominent as the
used. If you recall from volume conductor theory (see Chapter distal several centimeters of the nerve are common to all stimu
2), when two electrodes are placed relatively close together on lation sites and thereby not directly measured. When an NCV is
the same excited nerve, the propagating action potential is going measured, one must realize that the end result is a reflection of
to be detected at both electrodes. This is because the duration of the "average" NCV over the segment studied. The proximal
the SNAP is long enough to reach the E-2 electrode before it is portion of the nerve may be conducting slightly faster than the
completely extinguished at the E-1 electrode. The result is a distal segment, but the entire nerve segment is what is measured
cancellation of the first positive phase with an apparent initial for the calculation, thus reflecting proximal (faster) and distal
negative deflection thereby generating a biphasic potentia1. 30 (slower) aspects of the nerve.
Should the distance between the two recording electrodes be in When calculating sensory nerve NCVs, it is only appropriate
creased, or the E-2 electrode rotated off the nerve fibers, the ex to use the onset and not peak latencies. In this way, the fastest
pected triphasic morphology of the SNAP reappears (Fig. 5-17). conducting fibers are detected at both the proximal and distal
Onset Latency. Just as for CMAP studies, the onset latency sites of stimulation. Peak latencies do not reflect the fastest-con
is measured to the initial negative deflection of the SNAP (Fig. ducting fibers and are subject to uneven changes over distance
Chapter 5 NERVE CONDUCTION STUDIES - 181
because of temporal dispersion effects (see below and Chapter potentials. The end result can be a significant amount of phase
2). Peak latencies, however, can be used in isolation of onset la cancellation, generating a corresponding reduction in the
tencies and NCVs if reference data are presented for individual SNAP's amplitude.
nerves and standard distances. Rise Time. In biphasic SNAP responses the rise time is the
Negative Waveform/Spike. Because the SNAP may be time period from the potential's onset latency to negative peak
either biphasic or triphasic, the negative waveform portion of latency (Fig. 5-17). Similarly, in triphasic SNAPs, the rise time
this potential depends on the waveform's morphology. The is from the initial positive to subsequent negative peaks. The
SNAP's negative spike is that portion of the waveform between rise time is particularly important when performing near-nerve
the onset latency (initial negative or positive-to-negative deflec recordings, i.e., attempting to locate a needle active recording
tion) and where the negative spike intersects the baseline to electrode as close as possible to the nerve. In this technique, the
form the terminal positive phase (Fig. 5-17). needle electrode is placed in proximity to the nerve and moved
Duratiou. The duration of the SNAP may be either the nega in small increments while continuously stimulating the nerve.
tive spike's duration or the entire waveform's duration. The neg The optimal position for the recording electrode is determined
ative spike duration is calculated as noted above, i.e., from the by the rise time. The shortest rise time signifies that the needle
SNAP's onset to the intersection with the baseline. This para is next to the nerve. If the rise time increases, then movement is
meter is believed to be rather sensitive in assessing pathology, occurring in the direction away from the nerve instead of toward
but little reference data are available. Further work is needed in it. When using a near-nerve technique, the potential's morphol
this area to better define negative spike duration with respect to ogy is typically triphasic because the reference electrode is pur
its diagnostic utility. The total potential's duration is not rou posefully located at some distance from the nerve forming a
tinely used for diagnostic purposes. referential recording montage. Coincidentally, a maximal po
Amplitude. The SNAP's amplitude is usually measured tential amplitude usually corresponds to the shortest rise time.
from the initial baseline deflection or positive peak to subse Area. The area of the SNAP is characteristically determined
quent negative peak, i.e., baseline-to-peak or peak-to-peak. This by measuring that portion of the waveform demarcated by the
description may be somewhat confusing depending upon the negative spike. Area, like amplitude, is representative of the
SNAP's morphology and recording technique. If a bipolar number ofaxons depolarized. The area is not immune from the
recording technique is used where both electrodes are located effects of temporal dispersion arising from increases in distance
on the nerve and are relatively close together, an initial negative between the site of stimulation and recording. Care must be ex
deflection typically ensues. As already described for CMAPs, a ercised when attempting to define axonal loss based either on
more accurate reflection of the number ofaxons associated with area or amplitude for proximal sensory studies because of tem
neural depolarization is the negative spike's magnitude without poral dispersion effects.
considering the terminal positive peak. In motor fibers, collat Stability. Just as for CMAPs, the SNAP should remain es
eral sprouting of terminal axons following denervation can rein sentially unchanged from one stimulus to the next. A slight al
nervate newly denervated muscle fibers and increase the motor teration in the potential may occur secondary to baseline
units' muscle fiber content, thereby decreasing the accuracy of wavering because of the high amplifier sensitivities required to
motor amplitudes in defining axonal loss. The process of collat perform sensory studies. Should clearly recognizable changes
eral sprouting diminishes the correlation of the CMAP's ampli appear between successive stimuli, electrode movement or
tude with the number ofaxons excited over time. Sensory faulty electrode leads should be suspected, or intrinsic neural
nerves, however, do not sprout collaterals to replace lost fibers pathology causing drop-out of fibers or pathologic degrees of
but must regrow from the lesion site. Thus, a decreased ampli temporal dispersion.
tude comparatively more accurately reflects the axonal content
with respect to the number of functional nerve fibers. Therefore, COMPOUND NERVE ACTION POTENTIALS
when considering the SNAP's amplitude, one should really
measure it from initial negative onset to negative spike peak. If In addition to investigating pure motor and sensory nerve
an initial positive potential is present, as would be encountered fibers, it is also possible to study the action potentials from both
in referential recordings, or widely spaced electrode's on the sensory and motor nerve fibers simultaneously, i.e., mixed
same nerve, then the initial positive to subsequent negative peak nerves.27•39,47.114,115 When one attempts to record action potentials
most accurately reflects the number ofaxons excited. arising directly from a mixed nerve, the observed potential is
The magnitude of the SNAP's amplitude demonstrates a known as a compouud nerve action potential, mixed nerve
marked diminution from distal to proximal stimulation sites. action potential, or occasionally compound mixed nerve
This is the same phenomenon previously described for motor action potential. This technique is relatively simple and can be
nerves but is considerably more pronounced in sensory fibers. readily performed on most nerves. For example, suppose we
The explanation of the significant amplitude differences is pri wish to record the compound nerve action potential arising from
marily twofold. First, the duration of the SNAP's negative spike the median nerve in the forearm. One method is to record from
is shorter than that for the CMAP. This means there is less toler the median nerve at the antecubital fossa while stimulating this
ance for asynchronous summation at the recording electrode of nerve at the wrist. In this instance, the detected potential at the
sequentially arriving action potentials before phase cancellation elbow region consists of orthodromically conducting sensory
becomes a prominent factor (see Chapter 2). Secondly, the dis fibers and antidromically conducting motor fibers. A readily de
persion between the fastest and slowest sensory nerves is twice tectable potential is observed. The latency is usually measured
that for motor nerves at about 25 mis.n.73 When a nerve is ex to the potential's initial negative departure from the isoelectric
cited proximally, the increased distance traveled allows the tem line or first positive deflection if it is triphasic, thereby repre
poral dispersion between fast and slow fibers to become senting the fastest fibers contained in the nerve. It is also possi
prominent, which is manifested at the recording electrode as a ble to record from the wrist following stimulation at the elbow.
comparably asynchronous arrival of the multiple SNAP action The obvious difficulty commonly encountered with proximal
182 - PART" BASIC AND ADVANCED TECHNIQUES
stimulation is motor artifact arising from the activated forearm cm is to provide enough electrode separation to maximize the
muscles contaminating the mixed nerve response. Distal stimu SNAP's amplitude by ensuring that the potential's peak has
lation results in considerably less muscle artifact. passed by the E-l electrode before the initial aspect has reached
When conduction velocities are attempted for compound the E-2 electrode. If the interelectrode separation is too small,
nerve action potentials, one stimulus site is required. Recall that then the leading portion of the action potential detected by the
we are recording a response directly from a nerve without an in E-2 electrode is subtracted from the E-I electrode. ShOUld. the
tervening neuromuscular junction. As a result, the distance can peak of the action potential be under the E-I electrode at the
be directly divided by the response's latency after 0.1 ms (la same time the leading portion is under the E-2 electrode, the
tency of activation) has been subtracted. Compound nerve action amplitude of the negative spike is reduced. The magnitude of
potential data may be of benefit in the early diagnosis of periph reduction depends upon how close the two electrodes are to
eral entrapment syndromes. 312 Despite a few promising reports, each other. Four centimeters is chosen because the time neces
there are a few limitations regarding this technique. At the pre sary for the typical SNAP's peak to maximize is about 0.8 ms. If
sent time there are small numbers of normal values for only a the action potential's fastest-conducting fibers are propagating
few nerves. 39 Additionally, this technique has not been widely at 50 mis, then they have traveled 4 em in the time necessary to
applied to multiple diseases in orGer to fully characterize its clin reach the negative spike's peak (NCV 50 mls =distance/0.8
ical utility. The sensitivity and specificity of the compound nerve ms = 40 mm or 4.0 cm). Of course, it is not always feasible to
action potential must also be compared to pure sensory and achieve 4 cm of separation, e.g., short fingers in an antidromic
motor studies in pathologic situations. There have been sugges .recording. Also, it is important to remember that most elec
tions that it is inappropriate to equate compound nerve action po trodes imbedded in a plastic bar are not separated by 4 cm and
tential velocities with sensory velocities. One cannot assume that can result in artificially low amplitudes. The consequence of
the sensory fibers are preferentially the first and fastest fibers ex closely spaced electrodes is that the observation of small SNAP
cited simply because of the size principle. This cautionary note responses may cause one to erroneously conclude that axonal
is necessary because a study comparing sensory and motor loss is the reason for the amplitude reduction.
thresholds revealed that median nerve sensory thresholds were There is no optimal separation distance in motor studies. The
lower than motor fibers in only 56% of 55 digital nerves tested major consideration in studying CMAP's is to locate the E-I
and 40% of 37 nerves examined in the axilla. 30 electrode on the muscle's motor point while the reference elec
trode is placed in an electrically "silent" area, Le., on the
muscle's tendinous insertion. If the reference electrode is situ
FACTORS AFFECTING NERVE ated on muscle tissue innervated by the excited nerve, the
CONDUCTION STUDIES CMAP's amplitude will be reduced for reasons similar to those
noted above for the SNAP. Again, a low CMAP amplitude may
Prior to discussing the more commonly performed nerve con give the appearance of axonal or muscle fiber loss when it is
duction techniques, a number of issues regarding technical and merely an artifact of too closely spaced electrodes.
physiologic factors that can affect the NCS should be consid Filters. When the low-frequency (high-pass) filter is ele
ered. It is necessary for the practitioner to be cognizant of the vated above the frequencies contained in the waveform, signifi
various ways in which the measured SNAP and CMAP parame cant alterations in the potential's frequently measured
ters can be altered by either the instrument, electrodes, or pa parameters can occur. Specifically, for both SNAPs and CMAPs
tient. The reason these issues are important is because the amplitude decrease, peak latencies shorten, an extra phase
false-positive and occasionally false-negative results can arise appears, negative phase duration shortens, and the total poten
predisposing the unsuspecting clinician to an erroneous diagno tial duration decreases, but onset latency is unaffected. 7S·79 •so On
sis. Although the actual technical performance of the NCS is the other hand, lowering the high-frequency (low-pass) filter
relatively easy, the underlying physiologic mechanisms result below the frequencies contained in the waveform results in a re
ing in the detection of an impulse are by no means simple. duction in amplitude, increases in both the onset and peak laten
Careful study, however, allows one to readily comprehend these cies, and an increase in the negative spike's duration. Consult
principles and avoid diagnostic errors. Chapter 3 for a complete description of these changes and why
they occur.
INSTRUMENTATION FACTORS Amplification. Increasing the gain or sensitivity of the in
strument allows one to detect deflections from the baseline ear
One of the essential components of the electrodiagnostic lier than at comparatively lower amplifications. This has
medicine consultation is the instrument with which the patient's obvious implications regarding onset latency measurements.
electrophysiologic responses are recorded. As previously stated, Sweep Speed. When recording both SNAPs and CMAPs it
it is imperative for the practitioner to be fully aware of the in is good practice to use a sweep speed that allows the potential to
strument's capabilities and shortcomings. A poor understanding appear approximately in the middle of the CRT. This permits
of how the instrument processes the recorded signal can lead to the instrument to devote an adequate number of resolution
data misinterpretation. One of the most important concepts to points to avoid morphologic distortions secondary to subopti
remember when considering instrumentation effects is to use mal sampling frequencies. Additionally, if the sweep speed is
the same parameters at which the reference database was ac too low (e.g., 20 ms/div vs. 1 ms/div), the waveform is com
quired. Only a few of the more common instrumentation factors pressed into the stimulus artifact that can produce possible
are noted and the reader is urged to read the chapter addressing waveform distortions.
instrumentation in detail (see Chapter 3). Averaging. All commercially available instruments have the
Electrode Separation. When considering SNAPs, it is rec capability of avemging multiple stimuli in order to improve the
ommended that the active and reference interelectrode separation signal-to-noise ratio. When axonal loss results in potentials of
should meet or exceed 4 cm. 78--SO.84 This recommendation of 4 relatively small size, it is possible to erroneously consider them
Chapter 5 NERVE CONDUCTION STUDIES - 183
as part of the baseline noise, particularly if high amplifier gains placed 8 cm proximal to and directed toward the active record
are used. If these small potentials are dismissed as artifact, the ing electrode at the wrist over the median nerve and 20 cm prox
practitioner may be missing valuable diagnostic information. imal to the wrist site in the antecubital fossa. The separation
Averaging multiple response trials allows one to "extract" the between the anode and cathode is 2.0 cm. A nerve conduction
diminished potential from the surrounding background noise velocity of 50 mls is calculated with a distal CMAP onset la
that may be of equal magnitude as the response. As a result, it is tency of 3.0 ms. Suppose we now wish to repeat the study but
good practice when even the slightest doubt exists as to the inadvertently reverse the location of the cathode and anode at
presence of a response to employ the instrument's averager the wrist except with the anode now 8 cm proximal to the active
prior to concluding a potential is absent. recording electrode and hence the cathode 10 cm from E-l, The
Stimulators. Neural action potential generation occurs nerve conduction velocity is an intrinsic property of the nerve
about the region surrounding the cathode. As previously stated, and is not going to change irrespective of what we do with
convention dictates that a supramaximal stimulus be used at all recording or stimulating electrodes, thereby remaining 50 mls.
times when eliciting an action potential in the peripheral ner Originally the time required to traverse the 20 cm is 4.0 ms (50
vous system for NCV measurements. A byproduct of the stimu mls = 200 mmltime; time = 4.0 ms). By reversing the cathode
lation process may interfere with detection of the CMAP and and anode the interstimulus distance is now only 18 cm be
particularly the SNAP or compound nerve action potential. cause the cathode is 2.0 cm (cathode-anode distance) closer to
Impulse delivery from the stimulator is associated with an ini the antecubital fossa. The distal onset latency is subsequently
tial pulse of current/voltage from the cathode and anode, which prolonged by the time required for the action potential to travel
is conveyed instantaneously throughout that portion of the body the extra 2,0 cm between the cathode and anode, i.e., 0.4 ms,
enveloping the nerve, i.e., stimulus artifact. Because the Because we are hypothetically unaware of cathode/anode re
recording electrodes are located some distance from the source versal, the interstimulus distance is still measured at 20 cm
of the stimulus artifact, it can be regarded as a far-field potential when in reality it is 18 em. The actual interstimulus interval is
(see Chapter 2). A large stimulus artifact may have a sufficient no longer 4.0 ms but 3.6 ms because of the stimulus reversal
duration so as to coincide with the induced neural action poten (4.0 ms - 0.4 ms = 3.6 ms), The velocity is now increased to 55
tial. In this instance, the response of interest is either masked mls because our time has decreased (NCV = 200 mm (erro
completely or distorted to such an extent that latency and ampli neously measured)/3.6 ms = 55 mls). If this mistake is made
tude are of questionable value. There are a number of important initially as the only calculation, our NCV may be erroneously
actions the practitioner should take in order to minimize stimu high.
lus artifact. Reversing the cathode and anode also raises the possibility of
Simply, one wishes to have the stimulus artifact appear at the anode hyperpolarizing the nerve thus preventing conduction
both recording electrodes simultaneously and with the same through this segment of nerve, i.e., anodal block. The produc
magnitude. If the stimulus artifact appears equally at the E-I tion of anodal block is theoretically possible and has been suc
and E-2 electrodes, a substantial portion of the artifact will be cessfully performed in vitro.267 Anodal block does not occur in
eliminated through differential amplification and common routine clinical practice and can be ignored. By performing the
mode rejection. There are a number of ways to ensure this above noted stimulator reversal one can readily demonstrate
occurs. The impedance under both electrodes should be re that the latency prolongation is exactly what one would predict
duced and of a similar value with respect to the input imped based on distance effects of cathode/anode reversal without
ance of the amplifier thus ensuring a similar recording. Also, anodal block either blocking or slowing neural conduction.
both electrodes should be of the same type of material so the A potential problem associated with neural excitation is stim
signal is presented similarly at the amplifiers. Aberrant con ulus spread either longitudinally along the nerve beyond the site
duction pathways, surface collections of perspiration, or elec of stimulation or laterally toward other nerves. Recall that a
trode paste can preferentially convey the stimulus artifact to supramaximal excitation as previously defined is considered op
one of the two electrodes and should be avoided. A ground timal in exciting peripheral nerves. Increasing the intensity of
electrode located between the active recording electrode and stimulation can reduce the localization of neural depolarization.
stimulator also helps suppress some of the artifact. In addition A 4 times supramaximal stimulus intensity produces a decrease
to these precautions, one of the most useful ways to reduce in conduction time by approximately 0.75 ms. 262 Also, increas
stimulus artifact is to rotate the anode about the cathode, i.e., ing the stimulus intensity to just greater than supramaximal can
the cathode remains on the nerve while only the anode is repo shift the site of stimulus by 5 mm in older persons and 3 mm in
sitioned. This simple procedure helps to align the isopotential younger individuals. 30 This phenomenon is most likely sec
lines of voltage generated between the cathode and anode to ondary to the depolarizing pulse associated with the cathode ex
present in a similar manner at both recording electrodes assist tending within the body's volume conductor beyond the region
ing in common mode rejection. where the cathode contacts the patient. Nerves affected by
In addition to stimulus artifact, the practitioner should visu pathology can require significantly more current to achieve de
ally inspect the orientation of the cathode with respect to the E polarization, thereby increasing the possibility of stimulus
1 recording electrode. The cathode is usually positioned such spread and producing erroneously short latencies. Because the
that it is directed toward the E-I recording electrode. When per body's interstitial milieu is a relatively good conductor of cur
forming routine nerve conduction studies, there are only two ex rent flow, excess stimulus intensities can produce coactivation
ceptions to this rule, i.e., F waves and H-reflexes (see below). A of neighboring nerves to those intentionally excited. A typical
simple example will demonstrate the consequences of reversing example is median nerve stimulation at the wrist. If the current
the cathode and anode in relation to the active recording elec intensity is too strong, it is relatively easy to activate the ulnar
trode. 78- 8o,116,333 Let us suppose that we have located an E-l nerve. Should the median nerve conduction actually be patho~
recording electrode over the motor point of the abductor pollicis logically affected across the wrist requiring atypical current'in
brevis in the hand. For discussion purposes, the cathode is tensities for stimulation, and coincidentally, the electrode is also
184 - PART II BASIC AND ADVANCED TECHNIQUES
8 300
of variable separation results in a standard deviation 5.9 mlS.246
~IO In children, similar investigations demonstrate differences be~
500 tween successive days of up to 4 mls. It is possible to develop a
~ 5
simple formula in an attempt to quantify the amount of experi
IS 0+--.....,------"""""'1'
mental and biologic error typically present in NCVs. One can
o ID ro 30 ~ ~ W ro 80
begin by first considering the basic nerve conduction equation:
CONDUCTION VELOCITY (M I SEC)
C (nerve conduction velocity) = D (distance)/t (time).231 By
Figure 5-1 B. Conduction velocity error. A number of error taking the natural logarithm of this equation one can place it in
curves demonstrating the conduction velocity error (~C) as a func a format that can be readily differentiated, i.e., In C In D -In 1.
tion of conduction velocity at multiple distances. (From Maynard FM, Differentiating both sides of the equation results in: A (In C) = A
Stolov WC: Experimental error in determination of nerve conduction (In D) - A (In t). Because the derivative of (In x) is dx/x, we then
velocity. Arch Phys Med Rehabil 1972;53:362-372, with permission.) arrive at: AC/C = ADID Atlt. For convenience, the minus sign
in the above equation is converted to a plus sign as At can be
either positive or negative and the variables are rearranged. 231
spatially over the motor point of the adductor pollicis as well as The result is: AC = (ADID + Atlt) C. In this equation AC repre
the abductor pollicis brevis, coactivation of the ulnar nerve can sents the experimental error for a single NCV determination and
yield a false-negative onset latency. In this case a misdiagnosis is clearly dependent upon the error in measurement for both dis
might arise because the ulnar nerve's activation of the adductor tance (AD) and latency (At), and inversely dependent upon the
pollicis was recorded instead of the slowed conduction to the magnitude of the distance and conduction time. The error in
median nerve's abductor pollicis brevis muscle. Should stimu time measurement can arise from stimulus strength, identifica
lus spread be suspected, it is best to use a needle cathode and tion of the CMAP's onset, amplifier sensitivity, and subtraction
nearby surface or subcutaneous anode thus necessitating less errors. Distance measurements may result from limb position,
current, and decreasing the possibility of coactivating nerves or anatomic course of the nerve, cathode localization, skin-subcu
excessive current spread along the nerve. Neural stimulation taneous movement, skin movement during measuring, and tape
with either a needle or surface cathode at the same location pro measure reader error. The above equation attempts to better
duces no difference in the final NCV calculated. 334 define the time and distance errors in order to avoid some of
Measurement. When performing nerve conduction studies, these errors. Applying this equation in some simple examples
one must measure a number of parameters to arrive at the infor may help the practitioner conceptualize the diagnostic signifi
mation necessary for an appropriate diagnosis. Two of the most cance of time and distance errors.
fundamental parameters required in order to calculate a nerve Onset Latencies of Proximal and Distal Responses. If the
ulnar nerve is stimulated at the wrist and elbow, distal and prox
~45
SECONDS
1.0
imal onset latencies can be recorded for the abductor digiti
~ minimi's CMAP.231 At an amplifier sensitivity of 1000 flV/div
,40 the proximal and distal latencies are 5.58 ± 0.21 ms and 2.42 ±
~ 0.15 ms for a conduction time of 3.17 ± 0.25 ms, respectively,
'-35 1.25
)...
.... over a distance of 222.2 ± 1.8 mm. The manner in which the la
~30 l5 tencies were measured was by 20 skilled electromyographers
~ l75
reviewing a photograph of the trace and counting an electrical
:>:25
:;e: 2.0 time marker. Digital latency markers similar to those presently
~20 available on instruments were not used because the technology
~
2.'
did not exist at the time of the study. Given these differences,
~ 15
30
,.,
8 the principles of time error measurements continue to be valid.
4.0
~IO Because it is common to use two standard deviations, the exper
~~5.060
7.0 imental error for conduction time (At) and distance (AD) is 0.5
~ 5 ms and 3.6 mm for the nerve under investigation at an amplifier
~ o+---r---r--.--~----~--'--~~--~
o ID ro 30 40 00 ~ ro ~
setting of 1000 )lVIdiv. The experimental error for conduction,
CONOUCTION VELOCITY (hi I SEC I velocity for various conduction velocities and distances or con
duction times can be calculated, thus producing a table and
Figure 5-19. Conduction velocity error.A set of error curves family of curves (Tables 5-1 and 5-2; Figures 5-18 and 5-19).
revealing the conduction velocity error (~C) as a function of conduc The tables and experimental curves allow us to graphically visu
tion velocity at different times of conduction. (From Maynard FM. alize the relationship of experimental error to time and distance.
Stolov WC; Experimental error in determination of nerve conduction For example, if we assume a lower limit of normal conduction
velocity. Arch Phys Med Rehabil 1972;53:362-372, with permission.) for the ulnar nerve to be 50 mis, the experimental error equation
Chapter 5 NERVE CONDUCTION STUDIES - 185
provides us with some idea of the confidence with which the measured conduction velocity is normal within experimental
nerve can be judged normal based solely on experimental error. error. For a conduction distance of 150 mm, the AC is calculated
Suppose we consider a conduction distance of 250 mm for to be 13.6 mls. Our calculated conduction velocity of 60 mls
nerve fibers conducting at 60 mls with a resulting conduction may actually be as low as 46.4 mls. Because of the increased
time of 4.16 ms. Substituting the appropriate values into the ex experimental error secondary to a reduced distance of measure
perimental error equation yields: AC == 60 mls (3.6 mml250 mm ment, we no longer can state with 97% assurance that the NCV
+ 0.5 ms/4.16 ms) == 8.1 mls. The value of 8.1 mls represents we measured is normal. The experimental error tables and
two standard deviations about the calculated NCV with respect graphs (Tables 5-1 and 5-2; Figures 5-18 and 5-19) suggests that
to experimental error. Subtracting 8.1 mls from the measured 60 we should increase the distance over which the nerve's conduc
mls produces a normal conduction velocity of 51.9 mls. We can tion is calculated in order to reduce the experimental error into
state with 97% assurance (two standard deviations) that the an acceptable range, i.e., measured NCV is greater than 50 mls.
Table 5·2. Calculated Experimental Error (2 Standard Deviations) in Conduction Velocity (mls) for
Conduction Velocity. The experimental error curves for AC as standardized distances versus anatomic landmarks for recording
a function of distance and time reveal that experimental error is distal motor latencies or sensory latencies. 229,233,234 For example,
increased as the conduction velocity increases for a given dis it is intuitively obvious that there is a significant amount of in
tance or conduction time. Also, at any particular conduction ve terindividual variation regarding the size of one hand versus an
locity, the experimental error decreases as the conduction other. Examining distal motor or sensory latencies by placing
distance or time increases. In our above example, it can be seen recording or stimulating electrodes at a specified anatomic loca
that the final contribution to experimental error at 250 mm from tion or a number of centimeters proximal to it, predisposes one
distance (0.01) is less than that arising from time measurement to more variability and error. 194 A very large number of subjects
(0.12). The error in distance, therefore, contributes only 7.7% is necessary to account for the wide normal variation of hand
(0.13/0.01 x 100 = 7.7%) to the total experimental error while sizes. Also, to be completely representative, the effect of gender
time assessment contributes 92.3% to the error. This simple ex must be separately examined because of an anticipated gender
ample clearly illustrates the practical utility of being aware of ex hand size difference. Standardizing the distance over which a
perimental error and the necessity of carefully measuring distance nerve is measured, however, eliminates the above noted differ
and in particular latencies. It is also important to round off the ences and should generate much more uniform data with wider
calculated conduction velocity after the calculations. This implies applicability to the "normal" population. 194 A way to avoid this
that distances should be measured in millimeters and not rounded normal variation is to use conduction velocities. Reporting only
off to centimeters before the conduction velocity is calculated. distal motor or sensory latencies without a standard distance is
Amplifier Sensitivity. In the same investigation in which the less than optimal. It is also crucial to use standardized distances
above experimental error for time and distance were calculated, when defining reference data for sensory amplitudes. Small in
it was noted that the standard deviations at amplifier sensitivi creases in distance can profoundly affect the SNAP's amplitude.
ties of 5000, 1000, and 200 flV/div, respectively, for distal la Recording a SNAP amplitude and comparing it with a "norma
tencies were greater (6%,6%, and 9%) than those for proximal tive" data base using anatomic landmarks as opposed to stan
latencies (2%, 4%, and 4%). Additionally, the standard devia dardized distance is inappropriate.
tions or how much variation exists about the mean value, for Also, when measuring distances, one should record the dis
both proximal and distal latencies, are less at 5000 flV/div than tance between the center of two sequential cathode positions or
those at 200 flVIdiv. One explanation of these findings may be from the center of the cathode to the center of the E-l elec
that distal latencies are somewhat harder to accurately measure trode.250.333 This is because the stimulus is depolarizing the
because of the stimulus artifact typically interacting with the nerve about the cathode and is not displaced from it unless cur
onset latencies, particularly for short conduction times or rents significantly in excess of the supramaximal (as defined
recording distances. Also, at 5000 flVIdiv the onset of the po above) level are used. 116 Repositioning the anode about the cath
tential is better defined as it quickly arises from the baseline, ode does not affect the onset latency of a mixed nerve potential
while at higher sensitivities there is a more gradual baseline de thus demonstrating that neural excitation occurs in a region lo
parture as smaller changes are detected, thus resulting in more calized about the cathode and not some intermediate distance
uncertainty. Amplifier sensitivities at 1000 flV/div are interme between the cathode and anode. Stimuli delivered with 6 mm or
diate in terms of the standard deviations and is the reason some 20 mm diameter disc electrodes results in the same onset la
investigators prefer this setting to optimize onset sensitivity yet tency of the CMAP, thus suggesting that the nerve is activated at
minimize experimental error. Of course, more stimuli are re the center of each individual electrode supporting the con
quired as the amplifier must be adjusted to then record the entire tention that measurements should be performed from the center
magnitude of the potential that often exceeds the CRT's vertical of the stimulation site. 36
resolution. The sensitivity of 1000 flVIdiv is usually too high to Limb Position and Anatomic Nerve Course. A final note re
view the entire potential on the CRT. garding measurement factors affecting NCS is that of limb posi
Biologic Variation. Once the experimental error is quanti tion and anatomic course of the nerve. Studies comparing the
fied, it is then possible to calculate the amount of variation in presumed course of the forearm nerves by surface estimates
volved in nerve conduction velocities arising solely from versus actual anatomic course and length reveal that surface
"normal" biologic differences. Suppose the median nerve has a measurements are 3-8 mm shorter than the anatomic length. 36 A
conduction velocity 56.7 ± 3.8 mls64 over a distance of 250 mm I % length discrepancy in surface compared to actual length is
for a conduction time of 4.4 ms, and the distance and time errors noted in the peroneal nerve in the leg. s In addition to this, poten
noted above are operative. The experimental error contributing tial problem is the difference in surface compared to anatomic
to the conduction velocity is calculated to be 7.2 mls: AC = 56.7 measurements of nerves coursing across a joint. The most obvi
(3.6 mml250 mm + 0.5 ms/4.4 ms) 7.2 m/s. Because this ous example is that of the ulnar nerve traversing the elbow.
number represents two standard deviations, one standard devia Calculating ulnar nerve conduction across an extended com
tion is equal to 3.6 mls. The total variation is the summation of pared to flexed elbow consistently produces lower conduction
the experimental plus biologic variations, which is equivalent to velocities. 41 This slowing is obviously secondary to a measured
the square of the total variation consisting of the square of the distance too short for the actual length of nerve conveying the
standard deviations for the experimental and biologic varia electrical impulse. In the flexed position the nerve must be long
tions. 231 Applying this relationship to our data reveals that the enough to accommodate elbow flexion; therefore, the nerve be
normal biologic variation is approximately 1.2 mls: (3.8 mlS)2 = comes redundant in the extended position. Anatomic dissections
(biologic variation)2 + (3.6 mlS)2; biologic variation 1.2 mls. in cadavers confirm that the ulnar nerve buckles upon itself in
Applying these principles to any experimentally obtained data the extended positioned and unfolds with elbow flexion. 4 • 13o A
can yield the amount of variation resulting from normal in detailed discussion of the various techniques available for cal
terindividual variation and that arising from experimental error. culating ulnar nerve velocities across the elbow is presented
Standard Deviation vs. Anatomic Landmarks. An impor when ulnar nerve NCV techniques are described (see below).
tant issue with respect to measurement and NCV is the use of Obstetric calipers are recommended when attempting to measure
Chapter 5 NERVE CONDUCTION STUDIES - 187
nerve distances across a spiral pathway.250 For example, appro myelinated fibers proportional to the decreasing numbers of
priate uses of obstetric calipers may be in determining the posterior spinal nerve root fibers was noted. 51 A loss of fibers
length of radial nerve traversing the spiral groove, plantar was also noted in the peripheral and central projections of the
nerves from the sole of the foot to the medial malleolus, and acoustic nerve. Degeq~ration of the eighth nerve extensions was
transbrachial plexus measurements. also observed in the pathways through the brainstem into the
white matter of the cerebrum. l29 The optic nerve displays simi
PHYSIOLOGIC FACTORS lar changes to those previously noted for both peripheral and
central nerves,?1
There are a number of physiologic factors that have a direct Nerve Conduction Studies and Aging. One may consider
effect on nerve conduction studies. When considering physio either motor or sensory responses with respect to nerve conduc
logic factors, it is convenient for discussion purposes to divide tion studies and the effects of aging. Several generalizations can
them into those that can be altered by the practitioner and those be made regarding peripheral evoked sensory nerve actions po
intrinsic to the subject and beyond control. The most important tentials (SNAPs). The conduction velocity demonstrates a con
factor readily amenable to change is a limb's surface tempera sistent decline approximating 1-2 meters/second per decade
ture. A number of physiologic variables beyond the cpntrol of (Table 5_3).17.47,105,342 The SNAP's duration is about 10-15%,
the clinician are gender, age, height, digit circumference, and and 20% longer in the 40--60- and 70-88-year-old individuals
anomalous innervation. than the 18-25-year-old persons, respectively. Compared to the
Gender. Only a few studies have attempted to characterize 18-25-year-old group, the SNAP's amplitUde is one-half and
nerve conduction studies between males and females. There one-third, respectively, for the 40-60- and 70-88-year-old
was noted to be a slight increase in the antidromic sensory nerve groups.3O The distal sensory latencies revealed a similar prolon
amplitudes for both the median and ulnar nerves recorded from gation with age.
the digits in women. 17 Also, females demonstrated a greater The results of aging on conduction velocity have been exam
nerve conduction velocity for upper and lower limb nerves. 56•296 ined in a number of upper and lower limb nerves (Table 5-3).
Both of these differences, however, are minimized when one Motor nerve conduction velocities reveal similar changes to
considers limb length, height, and digit circumference (see sensory nerves. The newborn's motor nerve conduction veloci
below). 17.277.304 ties are about half of adult values, which are reached by 3-5
Aging. Histologic Alterations with Aging. The density of years of age. 6 After the age of 50 years, there is a progressive
large myelinated fibers in the distal portions of the sural nerve decline in the conduction velocity of the fastest motor fibers ap
increases rapidly from birth to 3 years of age and reaches a proximating 1-2 mls per decade. 120.230.246.349 There is a concur
stable adult value by 3 years. A maximum fiber density of 6480 rent increase in the distal motor latency and decrease in the
fibers/mm 2 is achieved by the third decade of life. The large motor response's amplitude with advancing age. The decrease
fiber density subsequently progressively declines to 54% (3480 in amplitude is difficult to ascertain clinically as there is such a
fibers/mm 2) of the second decade by 90 years of age. 332 After 60 wide range of normal.
years of age, stenosis of the vasa nervorum is rather pro The above nerve conduction study findings may be explained
nounced.52.332 One may conclude, therefore, that only about half to some degree by considering the histologic changes associated
of the large sensory myelinated fibers innervating the distal por with the aging of the peripheral nervous system. The maximum
tions of the lower limbs survive the aging process. Of additional
interest is the relationship between the distances separating the
nodes of Ranvier (internodal length) and diameter of myelinated Table 5-3. Decrease in HCV with Age
fibers. Below the age of 65 there is a linear correlation of intem per Decade After 20 Years of Age
odallength and diameter. At ages above 65 years there is less of Nerve NCV Range (mlsec)
a linear correlation and increased scatter of values, suggesting a Motor Nerve Conduction
shortening of the internodal length. 5.207 A lessening of the in Median 0.6-2.3
temodallength can result from demyelination and remyelina Ulnar 0.6
tion. 342 This process is ongoing with age and does not affect all Peroneal 0.4-0.8
of the large myelinated fibers equally. The above findings have Posterior Tibial 1.7
been documented in multiple peripheral nerves of both the
upper and lower limbs. Sensory Nerve Conduction
Histochemical studies of limb muscles from elderly individu With surface electrodes
als (65 years or older) without evidence of neuromuscular dis Median. orthodromic 3.0
ease revealed fiber size variation, hyaline or granular Median. antidromic 2.0
degeneration, loss of striations, clumps of pyknotic nuclei, in Ulnar. orthodromic 4.0
creased fat and connective tissue, and most significantly neuro With near-nerve techique
genic fiber type grouping. 161 .247 The fiber type grouping is more Median 1.8
pronounced in the lower than upper limbs and distally more Ulnar. up to 54 years 1.2
than proximally. The etiology of fiber type grouping was pre Ulnar. over 55 years 3.3
sumed secondary to degeneration and regeneration of the pe Ulnar 0.1
ripheral nervous system with secondary reorganization of the Sural. calf, orthodromic 0.5-1.1
muscle fibers belonging to individual motor units. Mixed Nerve Conduction
In addition to age-related changes of the peripheral nervous Median 4.0
system, the central nervous system also demonstrates alterations Ulnar 3.5
associated with aging. The most conspicuous changes were From Oh SJ: Clinical Electromyography: Nerve Conduction Studies. 2nd ed.
noted in the posterior columns. 236,251 A progressive loss of large Baltimore, Williams & Wilkins. 1993. with permission.
188 - PART II BASIC AND ADVANCED TECHNIQUES
adult nerve conduction velocities are achieved coincidentally muscles showed a systematic difference: the longer axons were
when myelination of the large fibers is completed, usually by alway slower in both the proximal and distal segment.371 This
the age of 5 years. 6.349 The subsequent reduction in sensory and was true for both arm and leg motor nerves. The additional
motor conduction velocity and amplitude with increases in the distal slowing due to tapering did not clearly add to this effect.
distal latency and response duration correlates well with ad These findings agree with anatomic studies indicating greater
vancing age. The aging nervous system demonstrates loss of nerve diameter in roots to proximal portions of the limb thap to
large fibers and evidence suggestive of progressive demyelina more distal muscles in humans. 27o Overall a slowing of 3.8 mls
tion and remyelination, particularly after the sixth decade.5.207.342 per every extra 10 cm of axonal length was found. 371 It can be
The combination of large fiber loss and segmental demyelina understood that this has a considerable impact on normal values
tionJremyelination has been suggested as possible cause leading given a range of body heights between 1.50 to 2 meters. It is be
to a slowing of conduction velocities. Buchthal has postulated lieved the previously noted gender differences for NCV are in
that the primary cause of the noted electrophysiologic changes reality height effects as women are characteristically shorter
is a direct result of an alteration in the nerve's membranous than men and display faster conduction velocities solely for this
properties required to sustain the appropriate current density reason. These height differences have not been found by all in
necessary for maximum conduction velocities. 30 vestigators and previous findings of neural conduction slowing
Digit Circumference. Females consistently demonstrate a with height have been ascribed to poor techniques and lack of
significant difference in antidromic SNAP amplitudes for the temperature controJ.336.337.371 Continued investigation is needed
ulnar and median nerves from the second and fifth digits. 17 A to further define the influence and etiology of height on NCV.
negative linear correlation exists between finger circumference Temperature. One of the most profound factors influencing
and amplitude for these two nerves. Additionally, it is known nerve conduction studies is temperature. In order to fully appre
that as the distance between the recording electrode and neural ciate the effects temperature can have on SNAP and CMAP pa
generator increases, the amplitude precipitously declines. rameters, it is perhaps best to first consider how a nerve's action
Increasing the circumference of the finger, especially with re potential morphology changes with different temperatures.
spect to subcutaneous tissue, displaces the electrode further When single myelinated fibers of the frog are cooled, a number
from the nerve. Men have significantly larger finger circumfer of interesting observations are made with respect to the nerve's
ences than women, thus providing a size difference explanation excitability and its action potential parameters. 291 As the tem
for the amplitude dissimilarities rather than an intrinsic neural perature of the nerve is lowered, the amount of current required
difference between male and female nerves. to generate an action potential increases. In other words, neural
Height. Several investigations have documented slower excitability is lowered with a reduction in temperature. This de
nerve conduction velocities in taller compared to shorter indi creased excitability is a direct temperature effect on the nerve's
viduals.34.202 This difference was found to be independent on the action potential generating mechanism at the nodes of Ranvier,
limb's temperature or subject's age. 105.106.202 Although the etiol and not a result of membrane resistance changes, i.e., the trans
ogy of this finding is unknown, an interesting hypothesis has membrane resistance is not increased by a drop in temperature.
been suggested to explain the observation. It is known that prox In addition to excitability, the morphology of an action potential
imal compared to distal nerve conduction velocities in different is profoundly affected by a drop in temperature.
nerves and more rostral nerve segments compared to distal por Effect on Action Potential. The action potential's amplitude
tions of the same nerve conduct faster.8.228.329 For example, com increases as the nerve's temperature declines. In addition to am
paring proximal median and ulnar motor NCVs to distal ones plitude, the action potential's rise and fall times are also in
revealed an 18% and 11 % greater proximal conduction velocity, creased. Specifically, the time required for the action potential
respectively.333 A 10-20% difference between proximal and to reach its peak depolarization from the resting membrane level
distal NCVs was found for lower limb sensory nerves. 8 Recall is increased approximately 33%. Also, the time necessary for
that nerve conduction velocity is proportional to axon diameter. the action potential to return to its resting level is also increased
It is suggested that the more proximal nerve fibers conduct com but much more so than the rise time (69%). Because both the
parably faster than the distal ones because the individual nerve's duration and spike height have increased, the area of the action
diameter tapers in the distal aspects of the limb, although some potential increases dramatically at lower temperatures. Similar
documentation exists to support distal tapering. 96 This is not data regarding action potential parameter changes at lower tem
universally found for all nerves. 270 Combining the above infor peratures are found in the giant axon of the squid, Le., increases
mation with the postulate that there is an abrupt decrease in the in action potential duration (rise time and descent time), spike
axonal diameter of individual nerves at some uniform distance amplitude, and area. l40 Application of the mathematical equa
from the anterior horn cell irrespective of the patient's height tions described by Hodgkin and Huxley for the giant axon of
has been suggested to account for the inverse relationship for the squid also predicts that the action potential should increase
height and NCV. If the axon suddenly decreases in diameter at a in amplitude as well as duration, and fall time greater than rise
set distance from the motor neuron, then tall persons would time, just as observed in animal preparations. Additionally, the
have a greater percentage of smaller axon diameters than short peak sodium conductance is also predicted to increase approxi
subjects for a given segment, such as the leg. The shorter per mately 38%.141
sons would still contain larger-diameter fibers when tall people Alteration of Conduction. A decrease in temperature is also
possess only small-caliber axons. Since NCV displays a linear found to alter conduction differently in nerves of various diame
relationship to axon diameter, it should not be unexpected that ters. The large-diameter fibers comprising the A group require
tall persons have demonstrably slower conductions than their less of a drop in temperature to produce action potential block
shorter counterparts. An alternative explanation is that long ade than the C fibers. Within the A fiber group, cessation of
axons are smaller and thus conduct slower from their origin. It action potential propagation following temperature reduction
was found that proximal conduction-measured by root stimu occurs first in the delta fibers and last in the alpha fibers.
lation--{)ver identical segments to proximally and distally located Comparing the motor and sensory fibers contained in the alpha
Chapter 5 NERVE CONDUCTION STUDIES - 189
size category, action potential propagation fails first in the sodium channels to flow for a longer period, i.e., by as much as
motor fibers. 74 The rate of NCV decline with a drop in tempera 3-4 times (see above). Because we know the resistance of the
ture is proportionately the same irrespective of the fiber's size, membrane changes minimally if at all, an increase in current
i.e., the rate of NCV drop per degree is the same for different should result in elevated action potential magnitude, i.e., Ohm's
nerves based on the percent of their normal NCV (see below). law states E = IR; if R is constant and I increases, then E must
Prior to myelinated nerve conduction failure at about 7-8°C, also increase. Indeed, as already demonstrated in several
NCV may be reduced to 1-2% of normal, i.e., for fibers with species, the nerve's action potential's amplitude and duration
conduction velocities of 6-100 mis, low temperatures (8-10°C) increase, particularly the action potential's decline associated
can produce conductions of 0.06 to 1.0 mlS.255.256 with sodium inactivation. Simply, if the sodium gates remain
Refractory Periods. The mechanism producing the above ef open longer, then current flows for an increased period of time,
fects may be understood jf one considers the nerve membrane's thereby generating a larger and longer action potential. Also,
refractory period. Following neural excitation, there are two failure of gate closure means there are more gates open for a
time periods of interest known as (I) the absolute refractory longer time period as not all the gates respond immediately but
period, and (2) the relative refractory period. For a short time stay open for variable time periods prior to closing. Thus, nor
period after an action potential, the nerve's membrane cannot be mally the gates that open first also close first. A drop in temper
excited irrespective of how large the depolarizing stimulus; this ature, however, causes these initially open gates to remain open
time is called the absolute refractory period. After the ab while their neighbors also begin to open, resulting in more cur
solute refractory period, a relative refractory period occurs rent flow. Therefore, delayed sodium inactivation appears to ex
during which an action potential can be induced, but only with a plain the morphologic alterations noted in action potentials with
stimulus intensity greater than that normally required. The time changes in temperature. We can now apply this information to
of the absolute refractory period is essentially the duration of whole nerves and understand the changes noted.
the action potential plus a subsequent short interval. Contained Local Cooling. Regarding sensory nerves in humans, two
within the absolute refractory period are sodium activation and different effects with respect to temperature must be considered:
sodium inactivation. The termination of the absolute refractory (1) local cooling, and (2) regional cooling. Local cooling is de
period is initiated by neural repolarization to where there are fined as decreasing the temperature of the nerve only about the
sufficient sodium gates available to again generate an action po E-! recording electrode site or for a finite distance within the
tential. In normal myelinated nerve fibers, the duration of the region of the recording electrode. If the sural nerve is recorded
action potential is about 0.4 ms with an additional 0.3-0.5 ms of posterior to the lateral malleolus and stimulated proximally,
membrane refractoriness for a total absolute refractory time of local cooling is accomplished by decreasing the temperature
roughly 1.0 ms with individual variations. The limiting factor in over the recording electrode only.203 The amplitude of the sural
how fast a nerve can conduct impulses is thus the absolute re SNAP increases as the temperature surrounding the active
fractory period resulting in a maximum firing rate of 1,000 Hz. recording electrode is decreased. Also, the rise time of the
The value in studying the refractory periods in nerve is that one SNAP is increased as the temperature is lowered. Upon rewarm
can gain indirect evidence as to how the sodium gates respond ing, the SNAP returns to its previous amplitude and rise time.
to temperature fluctuations that in turn yield information re Similar observations have been documented in other sensory
garding the mechanism of temperature effects on nerve mem nerves.18.19.2l1.214 These findings are certainly expected as the re
branes and NCVs. sponse of the entire nerve is merely the summation of what is
Decreasing the temperature surrounding human nerves alters occurring on a single-fiber bases. As previously described, indi
the absolute refractory period in a characteristic manner. vidual nerve fibers generate action potentials with increased
Lowering the temperature of median nerve fibers from 34°C to amplitudes, longer peak rise and fall times, as well longer total
20 c C results in an absolute refractory period change from 1.8 potential durations. The increased SNAP amplitude, negative
ms to 5.5 ms.63 The ulnar nerve sensory fibers demonstrated peak duration, and increased peak rise and fall times simply re
similar changes in the absolute refractory period of 0.54 ms to flect the composite changes occurring at the single fiber level
3.07 ms from 35°C to 20°C, respectively.212 Using a slightly dif because of delayed sodium inactivation. The net effect of all
ferent technique, median nerve sensory potentials demonstrated these physiologic changes is to slow the fastest-conducting
an absolute refractory period change from 0.8 ms to 1.8 ms for fibers somewhat more than the slower-conducting fibers.
temperatures of 36°C and 24°C. Relative refractory periods in Therefore, there is an increase in the temporal synchronicity
these same nerves were 2.5 ms and 10.0 ms, respectively. Mixed with which the individual nerve fiber SNAPs summate at the
ulnar nerve fibers demonstrated absolute refractory periods of recording electrode. A more synchronous arrival of individual
0.8-2.1 ms for fast-conducting fibers and 1.0-3.8 ms for fibers results in a significant increase in the composite SNAP
slower-conducting fibers.12.30.175-178.255.256 In mammalian nerves amplitude measured for all the fibers by the electrode.
the action potential occurs only at the nodes of Ranvier, which The CMAP arising from cooled muscle tissue demonstrates
contain significant numbers of sodium channels and essentially similar changes as those noted for SNAPs, although the increase
no potassium channels. 25 .46 As a result, the action potential of amplitude with cooling is less pronounced than that noted for
arises exclusively from sodium channel activation. The refrac the SNAP. 18,19.67 CMAP amplitude, duration, rise time, and area
tory period, therefore, essentially consists of sodium inactiva all increase as the muscle's temperature is reduced. Intra
tion and passive leak currents. Decreasing temperature alters muscular recordings also reveal that those motor units in close
sodium activation slightly but significantly affects sodium inac proximity to the recording electrode are also increased in the
tivation by slowing it down considerably.25.211 It has been sug same parameters noted above. 272 However, there is some dis
gested, therefore, that a prolongation of sodium inactivation is agreement in this area because one study documented a reduc
the major cause for increases in human nerve refractory periods tion in the motor unit action potential amplitude with a cooling
with cooling. The increased time of sodium gates remaining of muscular tissue. 29 It is these authors' opinion that lowering
open allows the depolarizing current associated with open muscular tissue temperature should result in an increase in the
190 - PART II BASIC AND ADVANCED TECHNIQUES
amplitude, rise time, and duration of the individual motor unit latency correlation of 0.2 ms/oC. Using this information al
action potentials as observed with needle electromyography. lowed a correction formula to be devised to correct median and
Unlike neural tissue, cooled muscular tissue demonstrates a ulnar motor or sensory NCV or distal latencies (DL) measured
resting membrane potential that fluctuates directly with alter at a particular temperature in the above-noted range to an opti
ations in temperature. 242 This fluctuation, however, is of ques mal skin temperature of 33°C, This formula is: NCV or DL(temp
tionable clinical significance at this point. Refractory periods in corrected) =CF (33°C - skin temp °C(measured» + NCV(calculateli) or
human muscle demonstrate increases in duration when the tem DL(ca1culated), where CF equals the appropriate correction
perature is lowered. 63.93 The magnitude of these temperature ef factor. 127 The same investigators also determined the correlation
fects reveals a 2.3 ms absolute refractory period at 34°C which between temperature and NCV in commonly investigated lower
is elevated to 9.3 ms at 20"C. The increased refractory period limb nerves. The peroneal nerve demonstrated a correction
suggests that the same mechanism of prolonging sodium inacti factor of 2.0 mlsl"C when the skin temperature is measured 15
vation applies to muscle membrane as well as nervous tissue. In cm above the lateral malleolus for a temperature range of
short, with respect to decreased temperature, CMAP and SNAP 26-32°C. Again a formula can be used to correct the observed
parameters demonstrate similar findings to local cooling of the NCV to a temperature of 32°C: NCV(tempcorrected) 2.0 (32°C
active tissue surrounding the recording electrode. skin temp °C(measured» + NCV(calculated). Finally, temperature cor
Relationship Between NCVand Temperature. In addition to relations for the tibial and sural nerves were also described for
the morphologic characteristics of the SNAP and CMAP, one the same surface temperature range measured 15 cm proximal
must also consider the rate at which sensory and motor action to the medial malleolus. Correction factors of 1.1 and 1.7
potentials propagate at different temperatures, i.e., the relation m/s/oC were used for the tibial and sural nerves, respectively.
ship between NCV and temperature. Based upon the single The tibial nerve correction formula is: NCV(temp corrected) = 1.1
nerve fiber's response to a lowering of temperature, prolonga (32°C - skin temp °C(measured» + NCV(Calculated)' For the sural
tion of the rise and fall time, we should be able to infer what nerve a correction formula is: NCV(temp corrected) = 1.7 (3ZOC
might be anticipated by the whole nerve's response to cooling skin temp °C(measured» + NCV(calculated)' If one is more accus
with respect to NCV. Because propagation is saltatory in myeli tomed to calculating sural nerve peak latencies for a 14-cm dis
nated nerve, the above effect of decreased temperature results in tance a correction formula may be used as follows: sural
an increase in the amount of time necessary to reach the action latencY(tempcorrected) = 1/{0.0l2 (32°C skin temp "C(me.sured» +
potential's peak at each node of Ranvier. As more time is re l/(measured latency)} .125
quired at each node, over comparable segments of nerve the Regional Cooling. As previously noted, local cooling pro
cooler nerve should have a slower conduction velocity. This is duces an increase in the duration, rise time, and amplitude of
exactly what is observed in coo] extremities when calculating both CMAPs and SNAPs. Regional cooling of a nerve segment
both sensory and motor nerve conduction velocities. over which conduction is measured, however, results in a pro
The first detailed investigation of temperature effects on longation of tbe response and possibly a slight decrease or no
NCV in human nerves revealed an NCV-to-temperature correla change in the amplitude compared to a warm limb. 310 This is a
tion of 2.4 mls/oC for median and ulnar motor conduction. 132 consistent finding provided the E-l recording site is not signifi
With every I ° drop in temperature, one could anticipate a 2.4 cantly involved in the temperature reduction. The explanation
mls decrease in the conduction velocity. Reductions in conduc for the drop in amplitude is most likely the result of a differen
tion velocity for upper limb motor nerve fibers have also been tial effect of temperature on NCVs for fast- as opposed to slow
found to approximate a decrease of 4-5% per degree conducting fibers. 62 The anticipated increase in temporal
Celsius. 56,163 Multiple investigations have revealed slightly dif dispersion would lead to a greater separation of fast and slow
ferent correlations between NCV and temperature, which is action potentials over the same nerve segment for a comparable
most likely due to different measurement techniques. One of the cooler segmental temperature. An increase in temporal disper
difficulties in attempting to define a relationship between NCV sion leads to greater phase cancellation and less phase summa
and temperature is deciding if surface, subcutaneous, or intra tion, thus producing a reduction in the evoked response
muscular temperatures are most appropriate. Because each of amplitude and area as well as a prolongation in the total poten
these three regions yields different temperatures for the same tial's duration. This concept may be better understood with an
site, it should come as no surprise that different correlations are example.
obtained for each depth. Fortunately, there is a linear correlation One way to study the effect temperature has on nerve con
between the three tissue depths justifying the use of surface duction velocity is to calculate the change over a 10° tempera
temperature measurements in attempting to calculate correction ture difference thereby producing a ratio known as QIO i.e., QIO
factors. 125 Of course, correction factors using subcutaneous and = NCV(T + lOoC)INCV(TOC)' For example, an NCV for the median
intramuscular readings are also correct. It is significantly more nerve sensory fibers at 37°C conducting over the wrist to elbow
convenient for most practitioners to use surface measurements. segment for the fast fibers is found to be 60 mls with a known
The studies that carefully attempted to control for temperature Q10 of 1.5. 62 The slow fibers are found to conduct at 30 mls for
and use standardized surface sites for measuring temperature the same temperature range with a similar QIO' The QIO is found
are described. 125- 121 to be the same for both slow- and fast-conducting fibers. 62 We
In the upper limb the relationship between temperature and can then ask, what is the temporal dispersion at 37°C and for a
NCV was investigated for the surface temperature range of 5°C drop in temperature over a 25-cm segment of nerve for the
26-33°C measured at the wrist's midline on the distal crease. fast- and slow-conducting fibers? First, we must find the tem
Calculations revealed that for median motor and sensory nerves, perature correction factor or just how much does the nerve con
NCV was altered 1.5 and 1.4 m/s/oC, respectively, while the duction velocity change per degree drop, By applying the QIO
distal latency for both changed 0.2 msfOC. The ulnar nerve ratio for a temperature range of 37°C to 27"C we discover that
demonstrated motor and sensory temperature relationships of the correction factor is 2.0 m/s/oC: (60 m/sh7'c/(Xh7'c = 1.5;
2.1 and 1.6 mls/cC, respectively, and a distal motor and sensory X27 C =40 mis, i.e., the conduction velocity for the fast fibers at
0
Chapter 5 NERVE CONDUCTION STUDIES - 191
27°C is 40 mis; (60 mis - 40 mis)110°C = 2.0 misrc. Applying correcting the NCV to a given temperature irrespective of the
the correction factor to our SoC drop yields a conduction veloc time involved. It is recommended that the practitioner use at
ity of 50 mis at a temperature of 32°C (2.0 mis/oC x 5°C = 10 least a surface temperature between the stimulating and record
mis drop in NCV, i.e., 60 mis - 10 mis = 50 mis). At 37°C the ing electrodes of 32°C and 30°C for upper and lower limbs, re
time required for the fast-conducting nerve fibers to traverse a spectively, to record data.
2S-cm neural segment is 4.2 ms (60 mis = 250 mmit; t =4.2
ms). The slow-conducting fibers cover this same segment of Anomalous Innervation
nerve at 37°C in 8.3 ms. The temporal dispersion, therefore, be There are a number of variants in both the upper and lower
tween fast and slow fibers at 37°C is 4.1 ms. The slow fibers limb with respect to muscular innervation. It is important for the
conduct at 25 mis at 32°C (apply above reasoning to arrive at practitioner to be fully aware of these so-called anomalous in
this solution) and have a correction factor of 1 misrc. Note that nervation patterns as they can often pose diagnostic challenges
for the same QIO the fast and slow fibers have different correc in various peripheral nerve injuries. We examine three upper
tion factors. Therefore, the conduction velocity for the slow and one lower limb diagnostically relevant innervation variants
fibers at 32°C is 5 mis less than at 37°C or 25 mis. At 32°C, the from an electrophysiologic perspective. The manner in which
temporal dispersion for the 25-cm cooled nerve segment be these anomalies present is stressed to avoid an erroneous con
tween the fast and slow fibers is 5.0 ms or a net increase of tem clusion given a particular set of findings.
poral dispersion of 0.9 ms. This difference increases if slower
fibers are considered, particularly at lower temperatures. It is UpperUmb
important to recognize the differential effect of temperature on Martin-Gruber Anastomosis. In the upper limb the
slow- and fast-conducting fibers through a region of cooled median and ulnar nerves normally travel as two distinct nerves
nerve producing temporal dispersion that tends to reduce the without an anatomic connection following their departure
amplitude of the recorded potential. Even though the action po from the brachial plexus. All of the forearm flexors are inner
tentials are increased for all cooled nerve fibers, the competitive vated by the median nerve except for the flexor carpi ulnaris
process with respect to amplitude of increased temporal disper (FCU) and the medial two muscle bellies of the flexor digito
sion and subsequent phase cancellation results in a compara rum profundus (FOP). It is possible for the median nerve to
tively smaller potential. This is just the opposite effect of local also supply the FOP to the fourth and fifth digits. Rarely, the
cooling that produces an increase in amplitude. If both the ulnar nerve may supply the FOP to the second digit. In the
region of nerve where the response is recorded as well as the hand, however, all of the intrinsic muscles are innervated by
portion conveying action potentials is cooled, the two opposing the ulnar nerve except for the abductor polIicis brevis (APB),
effects yield unpredictable responses; personal observations opponens pollicis (OP), one-half of the flexor pollicis brevis,
suggest that the response is delayed but the amplitude may be (superficial head) and the first two lumbrical muscles. This
larger than at a warmer temperature. classic innervation pattern generally serves the practitioner
Given the previous information regarding temperature and its quite well, but is certainly incomplete. A relatively common
profound effect on NCV, one can readily appreciate the neces communication between the median and ulnar nerves in the
sity of recording and attempting to control the temperature. A forearm is both clinically and electrophysiologically impor
cool limb, irrespective of the ambient room temperature, can tant, and should be understood by all individuals practicing
result in abnormal latencies, NCV s, and amplitudes. In short, a electrodiagnostic medicine.
normal limb can certainly yield abnormal results because of a The above-noted neural connection was first described
low temperature. An equally important issue concerns an abnor anatomically by Martin224 and Gruber121 resulting in the eponym
mal nerve, which is presumably why an individual is seeking associated with this anomaly bearing their names, i.e., Martin
the expertise of a specialist in electrodiagnostic medicine. Gruber anastomosis. The Martin-Gruber anastomosis is be
Although significant work has been performed in attempting lieved to have an autosomal dominant pattern of inheritance55
to define the necessary correction factors relating conduction and an incidence of 7.7_34%,123.153.221.315.316,355 with 68% of af
velocity with skin temperature, there remain serious questions fected persons having this anomaly bilaterally. 175 In 91 % of per
as to the relationship between abnormal nerves and how they re sons with the Martin-Gruber anomaly the anatomic connection
spond to temperature variationsJO.364 In a study carefully investi between the median and ulnar nerve is a communicating branch
gating the response of normal and abnormal nerves to reduced from the anterior interosseous nerve directly to the ulnar
limb temperature, healthy nerves responded differently than ab nerve. 3OS Because the anterior interosseous nerve does not typi
normal nerves. For the sake of brevity, let us consider only two cally convey cutaneous sensory fibers, this may explain why the
parameters, i.e., CMAP distal motor latency and SNAP ampli Martin-Gruber anastomosis typically does not affect sensation
tude. In normal persons the CMAP distal motor latency changed to the hand. Additional anatomic pathways include a branch
the expected amount of 0.28 ms/OC.19 The same parameter in from the flexor digitorum superficialis to ulnar nerve (6%) and
patients with compressive neuropathies and uremic peripheral a direct link between the main median and ulnar nerves (3%).308
neuropathies demonstrated changes of 0.40 and 0.23 ms/°C, re The nerve fibers involved in this anomaly are derived from the
spectively. SNAP amplitudes revealed an increment in normal C8/TI nerve roots, travel with the median nerve (anterior in
subjects of 1.96 J.lV1°C, while entrapment and uremic neu terosseous branch), and cross over to the ulnar nerve to primar
ropathies changed 0.94 and 0.84 J.lV/oC, respectively. Although ily supply the first dorsal interosseous (FOI) muscle 95-100%
it is recommended that applying correction factors are less time of the time, hypothenar muscles (41-61 %), and adductor polli
consuming than heating the patient,126 it is questionable how ac cis (AP) (14%).123.355 A number of reports state that the thenar
curately correction factors for temperature in normal persons muscle is innervated in the Martin-Gruber anastomosis. 175.355 It
apply to the individuals with abnormal nerves. Until more data is important to realize that this implies that the AP or flexor pol
are available regarding the best correction factor for diseased licis brevis are the muscles referred to and not the APB or OP.
nerves, warming of the limb should be considered superior to The Martin-Gruber anomaly does not refer to innervation of the
192 - PART II BASIC AND ADVANCED TECHNIQUES
typically median-innervated intrinsic hand muscles but to the positive deflection; however, with a concomitant Martin-Gruber
manner in which the ulnar-innervated hand intrinsics are sup anastomis as the motor point of the AP can occasionally align
plied by fibers that travel with the median nerve in the arm and with the surface APB recording electrode. A Martin-Gruber
forearm. anastomosis should be suspected in a median nerve lesion distal
Clinically, the Martin-Gruber anomaly is important because to the median/ulnar nerve anatomic connection when the fol
it is a way to convey innervation to the ulnar hand intrinsic lowing are observed: (l) initial positive CMAP deflection with
muscles despite an ulnar nerve lesion proximal to the commu proximal median nerve stimulation, (2) significantly elevated
nication between the median and ulnar nerve. For example, if median nerve NCV, or (3) larger proximal than distal CMAP on
the neural fibers in the anastomosis innervate the majority of median nerve stimulation. One would also anticipate that the
hand intrinsics, it is possible for the patient to sustain a com CMAP from ulnar-innervated hand intrinsic muscles with ulnar
plete lesion of the ulnar nerve at the elbow and continue to have nerve activation should be larger from the wrist compared to
a functional hand. Although the patient's strength in this case elbow stimulation. This is the expected finding and as a result is
may be somewhat reduced because of some concomitant inner often overlooked. Additionally, the ulnar nerve fibers traveling
vation from the main ulnar nerve fibers, the typical ulnar claw proximally with the median nerve may not innervate the ADQ
hand may not appear. This can give the impression of an "all and, therefore, not yield a noticeable difference. Unfortunately,
median hand" when indeed the innervation to the hand intrin the above-noted proximal and distal amplitude differences for
sics merely traveled with the median nerve proximal to the the median and ulnar nerve are not adequately quantified for the
ulnar nerve lesion. Nerve conduction studies in this patient Martin-Gruber anastomosis and are subject to the interpretation
would reveal that CMAPs are obtained from the ulnar-inner and experience of the practitioner.
vated hand intrinsic muscles to stimulation of the median nerve Ulnar-to-Median Nerve Communication. An electrophys
proximally, but not at the wrist, and a similar result with distal iologic communication conveying fibers to the median nerve
ulnar nerve excitation but not activation of the ulnar nerve from the ulnar nerve has not been documented in large detailed
above the lesion site. Needle electromyography may reveal ev series of patient studies. 178 A number of investigations using
idence of denervation in the ulnar nerve intrinsic muscles be surface electrodes or physical examination, however, have sug
cause of some fibers in the main ulnar nerve innervating the gested this type of connection. 174,191,222 These results must be
examined muscles were injured. questioned, however, because of the possibility of a connection
Observation of the Martin-Gruber anastomosis in routine between the median and ulnar nerves in the hand (see below)
nerve conduction studies requires a keen eye and knowledge of and volume conduction from various nearby muscles confusing
how the results differ compared to the classic innervation pat the electrophysiologic surface-recorded interpretation of vari
tern. Typically, the amplitude of the CMAP recorded from the ous findings. J 17 One well-documented case may represent the
APB and abductor digiti minimi (ADM) when stimulating the presence of this anastomosis. 314 The CMAP from the APB with
median and ulnar nerves, respectively, is somewhat larger dis median nerve stimulation was significantly smaller at the elbow
tally than with proximal nerve activation. This is because of less than wrist. In this case, the possibility of conduction block in
temporal dispersion of the individual action potentials with the forearm was not considered and may have explained the
distal stimulation (see Chapter 2). If a Martin-Gruber anastomo findings. In any event, prior to concluding that an ulnar-to
sis is present, the proximal CMAP with median nerve stimula median anomaly exists, other physiologic, pathologic, or tech
tion while recording from the APB is typically larger than that nical reasons should be considered.
obtained distally. This is because the nerve fibers contained in Riche-Cannieu Anomaly. Riche27I and Cannieu35 indepen
the median nerve at the elbow but destined to eventually join the dently described an anatomic communication of the median and
ulnar nerve are concomitantly activated at the elbow along with ulnar nerves in the hand between the recurrent branch of the
the median nerve fibers. The resulting volume conducted median nerve and the deep branch of the ulnar nerve. Although
CMAP from the AP, the deep head of the flexor pollicis brevis, largely ignored compared to the Martin-Gruber anastomosis, the
and possibly the FDI activated through the anastomosis sum Riche-Cannieu anastomosis is anatomically present in approxi
mates with that of the APB and OP to yield a larger proximal re mately 77% of hands. 131 The physiologic functional integrity of
sponse to antecubital fossa stimulation of the median nerve. this communication, however, remains to be documented.
When stimulating the median nerve at the wrist, the fibers trav Although there is little doubt as to the presence of this neural
eling with the median nerve destined to join the ulnar nerve connection, the exact percentage of either median or ulnar
have previously departed the median nerve proximally and are muscle fibers innervated through this anastomosis is unknown.
no longer capable of summating with the AP and OP. Clinically, it is possible for the ulnar nerve, through the
Should a lesion of the median nerve exist at the wrist (e.g., Riche-Cannieu anastomosis, to supply in part the thenar mus
carpal tunnel syndrome) with concomitant slowing of median cles normally supplied exclusively by the median nerve, thus
nerve conduction across this region, a somewhat different set of providing a dual innervation to these muscles. A complete
electrodiagnostic findings is noted. Stimulation of the median median nerve lesion at the wrist with clinical function of thumb
nerve at the wrist may result in a prolonged distal motor latency abduction and opposition has clearly been documented on mul
to the APB. Proximal median nerve excitation, however, pro tiple occasions. 48,241.280 It is this connection that most likely ac
duces a relatively normal proximal motor latency. The resultant counts for the so called "all ulnar hand." In such cases, one may
NCV is significantly increased to that above normal (50 mls) at anticipate that despite complete median nerve severance at the
times reaching 100 mls or more. It is also possible for the prox wrist, needle electromyography would reveal signs of denerva
imal motor latency to actually be shorter than the distal motor tion in the APB and OP, but a variable number of voluntary
latency.153 Additionally, one may commonly note that the motor units depending upon the extent of innervation by way
CMAP arising from proximal stimulation is not only larger than of the communicating ulnar-lo-median branch. One could con
that from the wrist, but also begins with a positive deflection. ceivably have an individual with both a Riche-Cannieu and
Proximal median nerve stimulation does not always require a Martin-Gruber anastomosis, thus allowing median nerve elbow
Chapter 5 NERVE CONDUCTION STUDIES - 193
stimulation to produce a response from the APB and OP with nerve at the ankle. Irrespective of the stimulus strength at the
variable responses from wrist stimulation. In this case, a com ankle, however, a larger response than that from the fibular head
plete severance of the median nerve at the wrist results in func should not be obtained. Clinically, a complete lesion of the deep
tional preservation of the typically median-innervated thenar peroneal nerve in the leg may spare the EDB leading one to er
muscles, i.e., an all ulnar hand. Failing to understand the Riche roneously conclude that there is an incomplete peroneal nerve
Cannieu anomaly can lead to potential confusion. It may also be lesion. Failure to recognize this anatomic variant may also pre
possible for the ulnar nerve itself to provide direct neural com dispose one to conclude that some corrective surgical procedure
munication to all of the thenar muscles obviating the necessity may have led to improvement when indeed the accessory per
of a Riche-Cannieu anastomosis, but this is a rare occurrence. 324 oneal nerve is providing the EOB's innervation. Preservation of
Finding signs of denervation in the ulnar-innervated muscles, the EDB and peroneus brevis and longus muscles despite lack
the APB, and OP would normally lead one to suspect the possi of voluntary motor unit activity in the tibialis anterior or exten
bility of a C8rrl or brachial plexus injury. A complete diagnos sor digitorum muscles should cause one to suspect the possibil
tic assessment, however, failed to reveal such a lesion in just ity of an accessory deep peroneal nerve.
such a patient. so Careful clinical examination in this person re It is relatively easy to confirm the presence of an accessory
vealed that the ulnar nerve demonstrated a lesion at the elbow. deep peroneal nerve. When one encounters a larger peroneal
Intramuscular recording techniques combined with selective nerve response from the EDB with fibular head compared to
neural blockade demonstrated a connection between the median ankle stimulation, one should first ensure proper activation of the
and ulnar nerve in the hand thus accounting for the APB and OP peroneal nerve at the ankle: Occasionally, the nerve may lie rather
findings. An initial awareness of this simple anatomic connec deep to muscular and tendinous tissues. Increasing the current
tion would have resulted in the institution of proper treatment at strength and duration should result in an increase in the magni
a more appropriate time interval. tude of the EDB's CMAP. If the response does not change, stimu
lating posterior to the lateral malleolus while recording from the
LowerUmb EDB then results in a response. Summating the EDB's CMAP
Accessory Deep Peroneal Nerve. In the lower limb an ex from both the anterior and lateral stimulation sites should slightly
tension of the superficial peroneal nerve, the accessory deep exceed that obtained from the fibular head. If signs of complete
peroneal nerve, proceeds posterior to the lateral malleolus to denervation (florid membrane instability and absent voluntary
then innervate the lateral portion of the extensor digitorum motor units) are noted in the muscles innervated by the deep per
brevis (EDB) muscle. 361 The EDB, therefore, can receive dual oneal nerve except the EDB, one should consider the possibility
innervation from both the deep peroneal nerve and the acces of an accessory deep peroneal nerve and proceed with the above
sory deep peroneal nerve. Investigations of normal populations noted stimulation technique. Caution is recommended when
have revealed that the accessory deep peroneal nerve may exist stimulating posterior to the lateral malleolus and recording from
in up to 28% of persons with 57% of those individuals having it the EDB. When an excessively strong current is used, a volume
bilaterally.I23·lsl,I96.244 There is also the suggestion that an auto conducted response from the foot intrinsic muscles other than the
somal dominant inheritance pattern may be present. 54 This EDB can be detected because of tibial nerve depolarization. The
anomaly may be a cause of confusion if the practitioner is un initial positive deflection should result in the discarding of this
aware of this variant. Specifically, stimulating the peroneal potential and not concluding that an accessory peroneal nerve is
nerve about the fibular head typically results in a CMAP from present. However, a negative deflection may be observed because
the EDB with a smaller magnitude than that evoked from the of a spatial alignment of the foot intrinsic muscles' motor point
ankle. This is a result of less temporal dispersion of action po with the recording electrode may occur. It is always a good prac
tentials distally compared with proximal nerve stimulation. A tice to place a concentric needle electrode in the muscle to verify
larger amplitude proximally may lead one to consider the possi that a volume-conducted potential is not present as the needle
bility of a less than supramaximal stimulation of the deep peroneal electrode is less prone to recording volume-conducted potentials.
Table 5-4 summarizes the different possibilities for the major cutaneous fibers of the median nerve extending from the tip of
nerves that should be considered upon encountering an unex the digits to about the interphalangeal region. However, the
pected higher or lower CMAP at distal or proximal stimula motor fibers from the C8 and TI levels innervate the hand in
tion. 365 It is always wise to have an extra channel available to trinsic muscles while C6-Tl cervical levels innervate the fore
have the possibility of simultaneous recording an extra muscle arm and hand extrinsic muscles. The motor fibers of the median
to exclude or prove costimulation or the existence of an ana nerve are commonly investigated by evaluating nerve conquc
tomic variant. tion to the median-innervated thenar muscles (APB, OP, and
one-half of the flexor pollicis brevis). Conduction studies to the
first and second lumbrical muscles are possible, but not rou
NERVE CONDUCTION TECHNIQUES tinely performed.98 When performing nerve conduction studies
to the thenar muscles, therefore, motor fibers arising primarily
Once the above-noted fundamental aspects of the peripheral from C8 and Tl are evaluated. It is possible to evaluate the am
nervous system and the various factors influencing peripheral plitude change across the transverse carpal ligament with stimu
nerve action potential propagation have been mastered, it is ap lation proximal and distal to the ligament. 259 This method of
propriate to consider diagnostic nerve conduction studies. The median nerve assessment permits one to determine if there is
technical aspects of stimulating and recording potentials from conduction block of median motor fibers as they traverse the
the peripheral nervous system are relatively straightforward. carpal tunnel region. Caution must be exercised when perform
The intent of this section is not to present an encyclopedic litany ing this study because it is relatively easy in some individuals to
of every NCS described, but to familiarize the practitioner with also activate the ulnar nerve's deep branch that lies just deep to
the more common diagnostic techniques available. Additionally, the median nerve's recurrent branch in the palm. Therefore, the
proper technical skills are stressed that can be applied to less CMAP morphology above and below the carpal ligament must
commonly used nerve conduction studies. Upper and lower be very similar, otherwise ulnar activation is likely and the re
limb motor and sensory nerves are described as well as nerve sponse can not be accurately evaluated.
root stimulation and additional techniques. Recording Electrodes. For motor nerve conduction studies.
Although there are mUltiple techniques reported to evaluate E-l is preferentially located on the muscle's motor point under
motor and sensory fibers, very few control for temperature and investigation (Fig. 5-20). The motor point of most small mus
distance, or clearly report the amplifier gain and filter settings. cles is approximately one-half the distance between the
The effects of distance and temperature on nerve conduction ve muscle's origin and insertion. Muscles with long tendons pos
locity have already been stressed. A lack of control for tempera sess somewhat more difficult motor points to define, but these
ture and distance predisposes one to a less than standardized are mentioned in detail when discussed. Prior to securing the
methodology inviting inter-individual variation, thus diminish recording electrodes to the patient, it is recommended that the
ing the sensitivity of the test. An attempt is made at including skin be slightly abraded to reduce the impedance and a mod
only the investigations using a standardized distance where icum of electrode gel be applied. Enough tape or other securing
some mention of temperature is described. material should fasten the electrodes securely to the patient to
avoid movement artifact. E-2 is best located at or just beyond
the muscle's tendinous insertion away from E-l on the first
COMMON UPPER LIMB NERVE digit. Similar comments noted above are appropriate for all
CONDUCTION STUDIES recording electrodes irrespective of the nerve being studied and
will not be repeated for each nerve discussed.
UPPER LIMB MOTOR NERVE CONDUCTION STUDIES £-1. The E-I electrode is positioned on the thenar eminence
halfway between the midpoint of the metacarpophalangeal
A pertinent aspect of performing motor nerve conduction joint's volar aspect for the first digit (thumb), and the midpor
studies is placing the E-l electrode on the muscle's motor point tion of the distal wrist crease (Fig. 5-20). This site should ap
that is innervated by the nerve under investigation. The E-2 proximate the most prominent portion of the thenar muscles.
electrode is located on a relatively electrically silent region, i.e., Slight repositioning of E-I may be necessary to obtain an opti
the tendinous insertion of the muscle studied. A ground elec mal CMAP response as defined by an immediate negative de
trode is then placed just proximal to E-l between it and the flection following median nerve excitation.
cathode. The stimulator employs a supramaximal pulse to evoke £-2. The actual distance between E-2 and E-I is really not
a CMAP from at least two and possibly more locations along critical provided the distance is not too close. The most conve
the nerve's peripheral extent. The NCS's parameters of interest nient location is just distal to the insertion of the APB approach
are: CMAP's amplitude, CMAP's onset latency, also called ing the first digit's distal interphalangeal joint (Fig. 5-20).
distal motor latency (DML), and NCV. Ground. The ground electrode should be secured to the pa
tient following appropriate skin preparation to ensure a low skin
Median Nerve impedance. The most appropriate location for any ground elec
The median nerve is a mixed nerve composed of motor fibers trode is adjacent to E-l between the stimulator's cathode and E
arising from cervical and thoracic root levels C7-Tl, and sen I. It is assumed that this is the position for all nerves examined
sory fibers from cervical levels C6-C7 .144 The median nerve's unless otherwise stated.
cutaneous distribution encompasses the volar aspect of the lat Stimulation. The cathode is positioned over the median
eral two-thirds of the hand and three and one-half digits begin nerve such that it is directed toward E-I while the anode is lo
ning with the thumb. 206 This nerve supplies C6 cutaneous fibers cated away from E-I. This distal cathode and proximal anode
to the thumb and index finger while providing C7 fibers to the relationship is assumed to be the case in all following nerves in
third and one-half of the fourth digits. Additionally, the dorsal vestigated unless specified. With respect to the median nerve,
aspect of the three and one-half digits are also innervated by the the distal site of stimulation is at the wrist between the tendons
Chapter 5 NERVE CONDUCTION STUDIES - 195
Table 5-5. Median Nerve: Motor are necessary to assess the electrical integrity of the nerve
DML (ms) Amplitude (mV) NCV (m/s) through the above-noted areas.
One of the major sources of contention regarding ulnar nerve
3.7 ± 0.3 (3.2-4.2) 13.2 ± 5.0 (.5--25) 56.7 ± 3.8 (50.0-67.3) conduction studies is the position of the elbow. Because the
8.8 ± 3.1 (3.5-15)
ulnar nerve can be compromised at the level of the elbow, it be
Mid-palm Amplitude (% change)'
comes necessary to determine the optimal position of the elbow
8 ± 8.5
when performing nerve conduction studies across this segment.
Temperature was not recorded for these values. Amplitudes are measured There is noted to be a significant difference in conduction ve
peak-to-peak except for mid-palm study. Amplifier sensitivity is set at 1,000 locity across the elbow depending on whether the elbow is
I.LV/div, and filter settings are 8 Hz to 8kHz.m.2"
• Amplitude for transcarpal values are reported in percent change with any flexed or extended, and to what degree. The nerve conduction
change greater than 25% considered abnormal. 259 DML, distal motor latency; velocity is markedly slower with elbow extension compared to
NCV, nerve conduction velocity. flexion. This finding is believed to occur because of the nerve
length required to extend across the elbow in the flexed posi
Generally, the recorded potential should appear near the middle tion without rupturing and subsequently becoming slack and
third of the CRT so as to avoid the stimulus artifact contaminat redundant with elbow extension. 41 Although the length of nerve
ing the desired response. A sweep of 2 or 5 ms/div typically does not significantly change between a point above and below
suffices for most routine studies of the forearm. Should exami the elbow, a discrepancy occurs with respect to the surface dis
nation of the arm be required, a sweep speed of 5 ms/div is pre tance measured in flexion versus extension. In extension, the
ferred to visualize the response. measured distance is shorter compared to the same points when
Perhaps the most variable and least universal instrument pa the elbow is in flexion. When calculating a nerve conduction
rameter is the high- and low-frequency filter settings. The band velocity, essentially the same time of conduction for both posi
width noted for the included reference data is 8 Hz to 8 kHz. tions is divided into a longer distance for flexion compared to
Some variation about these numbers should not dramatically extension thus resulting in a larger value for the NCV. There is
alter the CMAP morphology provided the low- and high-fre no change in the CMAP's duration or amplitude when recorded
quency responses do not restrict the bandwidth in excess of 10 in flexion compared to extension. 41 The only parameter that
Hz t05 kHz. changes is the NCV because of the difference in distance mea
Reference Values. The reference data utilized in this text is sured when the elbow is flexed. Normal values are provided for
derived using the above noted instrumentation parameters both extension and flexion for the across elbow ulnar nerve
(Table 5_5).233.234 Any significant deviation from the instrument segment (Table 5-6).41.184 A comparison of nerve conduction in
settings requires the practitioner to develop a new set of refer the distal segment of the ulnar nerve is also provided. Because
ence data. Mid-palm amplitudes are noted, however, latencies of a possibility of compromise preferentially involving the
were not reported. 259 deep branch of the ulnar nerve distal to the innervation of the
abductor digiti minimi, a technique is described comparing la
Ulnar Nerve tency differences between the abductor digiti minimi and first
The ulnar nerve is comprised of motor and sensory fibers dorsal interosseous.
originating primarily from C8 and Tl cervical root levels. l44
Cutaneous fibers of the ulnar nerve innervate the volar aspect of Ulnar Nerve Conduction: Forearm, Elbow. and Arm
the palm as well as the fifth and one-half of the fourth digits. 206 Recording Electrodes. The first technique involves ulnar
The cutaneous sensibility also innervates the dorsal aspects of nerve conduction in the forearm, across elbow, and arm seg
these digits to approximately the proximal interphalangeal joint ments recording from the abductor digiti minimi muscle. A
region. The dorsal aspect of the hand and remaining portion of second technique investigating conduction in the terminal ex
these digits is innervated by the dorsal ulnar cutaneous nerve. panse of the ulnar nerve within the hand records a CMAP from
There is believed to be a motor contribution from the C7 level, not only the previously noted muscle but also the first dorsal
particularly innervating the flexor carpi ulnaris. The muscles in interosseous. 252
nervated by the ulnar nerve in the forearm are the flexor carpi E-1. An E-l electrode is secured to the motor point of the ab
ulnaris and the flexor digitorum profundus to the fourth and ductor digiti minimi. This is accomplished by locating the
fifth digits. Anatomic variants to the flexor digitorum profundus halfway point between the distal wrist crease or pisiform bone
exist, but are not discussed in this portion of the text. All of the and the metacarpophalangeal joint of the fifth digit (Fig. 5
hand intrinsics are innervated by the ulnar nerve except for 20).41.233.234 This distance is measured on the most medial aspect
those previously noted to be supplied by the median nerve. This of the hand over the muscle's main bulk.
nerve is essentially a direct extension of the brachial plexus' E-2. The E-2 electrode can be positioned over the distal
lower trunk and medial cord. The nerve is secured at the inter aspect of the digit or just distal to the metacarpophalangeal
muscular septum in the arm (arcade of Struthers) and somewhat joint. A "bar" recording electrode should not be used to ensure
restricted between the two heads of the flexor carpi ulnaris the reference electrode is not located over muscle tissue.
muscle. Between these two anatomic regions the nerve is rela Stimulation. The ulnar nerve can be stimulated in at least
tively exposed about the ulnar groove at the elbow in that it is four locations to evaluate conduction over various neural seg
subcutaneous and vulnerable to trauma. There is also a possibil ments. 41 ,184 Let us ftrst assume that the elbow is flexed. For dis
ity that the ulnar nerve may become entrapped within the sub cussion purposes, within this text the elbvw is fully flexed to
stance of the flexor carpi ulnaris muscle. A second possible site approximately 135° with the forearm supinated (Fig. 5-21). The
of ulnar nerve compromise is at the wrist within the canal of arm and forearm are positioned for maximum patient comfort.
Guyon as the ulnar nerve traverses the region between the pisi One way to achieve this goal is to have the patient abduct the
form bone and hook of the hamate.313 Because of these possible arm 90° and rest it on a pillow such that the hand approximates
anatomic regions of compromise, electrophysiologic techniques the ipsilateral ear. This position exposes the desired stimulation
Chapter 5 NERVE CONDUCTION STUDIES - 191
sites while simultaneously relaxing the patient and allowing the ulnar groove. The two stimulus points should first be delin
easy measurement of the desired neural segments. eated on the patient. A tape measure is then secured to the
It is desirable to only stimulate the nerve at fixed distances to below-elbow site and carefully placed just posterior to the
minimize anatomic variability and inter-observer variation due medial malleolus and then proximally along the medial aspect
to distance measurement errors and uncertainty. One particular of the arm to the above-elbow site. In the flexed position, one
study is used for uniformity of data; however, one may wish to may first wish to optimize the ulnar nerve CMAP with respect
use slightly different distances for the distal site as this should to amplitude to accurately locate the ulnar nerve as it is often
not significantly affect the nerve conduction velocity. surrounded by subcutaneous tissue impeding ulnar nerve palpa
Specifically, a distance of 6.5 cm proximal to E-I along the tion. 85 Several measurements may be necessary to ensure the
ulnar nerve at the wrist is one recommendation but 8.0 cm may most accurate distance.
also be used. 41 ,184 The only caution is to use the appropriate ref The ulnar nerve can also be excited at the above-noted four
erence data for distal latencies for each respective distance. A stimulation sites with the elbow in 180 0 of extension.41.184
second site of stimulation is 4 cm distal to the medial epi Unlike elbow flexion, the stimulation sites are less well exposed
condyle. 184 The third stimulation point is at least 10 cm proxi and the examiner experiences somewhat more difficulty in at
mal to the below elbow stimulation area. Finally, the fourth tempting to measure and stimulate the appropriate neural seg
position for the stimulator is 11 cm proximal to the above-elbow ments. For localizing an entrapment of the ulnar nerve at the
site. With this technique one can assess 5 separate neural seg elbow it may be necessary to use a shorter segment over the
ments: (1) forearm, (2) across elbow, (3) arm, (4) above elbow elbow in order to measure a slowed conduction velocity. It is
to wrist, and (5) wrist to recording electrode. Of course, should also possible to stimulate the ulnar nerve in short segments of 1
the clinical situation arise, it is relatively easy to also stimulate cm over a presumed lesion to help better localize the exact site
the ulnar nerve in the axilla or its constituent fibers from supra of pathology.169 If short segmental stimulation is to be used, it is
clavicular activation. It is necessary to discuss the measurement essential to ensure accurate nerve activation. Recall that neural
technique across the elbow. excitation of a nerve that lies deep to muscle and subcutaneous
A certain amount of practice is required to accurately mea tissues (ulnar nerve deep to the flexor carpi ulnar muscle) may
sure the across-elbow segment with the elbow fully flexed. It is require an elevated stimulus intensity/duration, which predis
best to pursue the anatomic course of the nerve as it traverses poses to errors between the presumed and actual site of nerve
198 - PART" BASIC AND ADVANCED TECHNIQUES
stimulation. In the authors' opinion, it is best to perform short loss as opposed to demyelination. Therefore, the needle elec
segmental stimulation with a needle cathode to minimize the tromyographic examination usually detects an abnormality
amount of current spread between the site of skin penetration prior to the latencies reaching the above-noted abnormal values.
and neural activation.
Instrument Parameters. The amplifier sensitivity can vary Radial Nerve
between 1,000 and 5,000 IlV/div and is specified in the table de The radial nerve is a direct continuation of the posterior cord
lineating the reference data. A sweep speed of 5 ms/div is as of the brachial plexus. Cervical root levels C5-C8 and occasion
sumed for most motor studies particularly when examining the ally Tl comprise the neural fibers forming the radial nerve. 144
more proximal neural segments. Filter settings are important and After traversing the spiral groove about the humerus, the radial
should be reproduced with respect to the reference data used. nerve enters the forearm. The superficial radial nerve, a pure
Reference Values. Two sets of reference data are included sensory nerve, arises from the main trunk of the radial nerve fol
for both the flexed and extended position (Table 5_6).41.184 lowing innervation of the extensor carpi radialis longus. This
Despite different filter and gain settings there is good agreement nerve provides cutaneous sensibility to the dorsum of the hand
between the two studies. A value of less than 11.4 mls is noted not innervated by the median and ulnar sensory nerves noted
when comparing across-elbow conduction velocities with those above. The continuation of the radial nerve innervating the re
in the forearm. 184 mainder of the hand's extrinsic extensor muscles is referred to
as the posterior interosseous nerve. The terminal muscle inner
Ulnar Nerve Conduction: Hand vated by the posterior interosseous nerve (C7 and C8) is the ex
Recording Electrodes. A lesion affecting the deep palmar tensor indicis proprius.
branch of the ulnar nerve may occur distal to the innervation of Recording Electrodes. The placement of recording elec
the ADM but prior to the innervation of the AP or FDI. In this trodes for this nerve is somewhat more technically demanding
case, it would be of value to compare the time of conduction than for the median or ulnar nerves. This is because the usual
through the potentially affected deep branch to the motor inner site of E-l placement, extensor indicis proprius, is not as
vation to the ADM. A comparison technique is described to anatomically prominent as the thenar or hypothenar groups.
assist in the diagnosis of possible injury to this nerve. Bony anatomic landmarks are therefore necessary to ensure
£-1. The E-I electrode is located on the abductor digiti proper electrode placement. The commonly used techniques re
minimi as noted previously (Fig. 5-20). A second E-l electrode quire that a standard concentric needle electrode be placed
is placed over the first dorsal interosseous over the muscle's within the extensor indicis proprius muscle. A needle electrode
major protuberance. located within a muscle helps to ensure that the observed re
£-2. An E-2 for the abductor digiti minimi is positioned on sponse arises from only the desired muscle. However, because
the fifth digit distal to the muscle's insertion. The recommended of a needle E-l electrode, amplitudes are of limited value par
position for the first dorsal interosseous muscle's B-2 is on the ticularly in attempting to define axonal loss or conduction
second metacarpophalangeal joint. 252 One may wish to place E block. Recall that the muscle as a whole is not evaluated but
2 distal to the first metacarpophalangeal joint; however, in order only the fibers located within a short distance of the E-I record
to reduce an initial positive deflection occasionally observed ing surface.
with the previously noted E-2 placement. The use of surface electrodes to record the radial nerve re
Stimulation. The ulnar nerve is stimulated at the distal wrist sponse has been suggested;215.216 however, one must be prepared
crease in the original study. Although a standard distance is pre for a positive deflection as it is very difficult to locate the exten
ferred, it is acceptable to use an anatomic location in this in sor indicis proprius or any other radial nerve muscle's motor
stance because the parameter of interest is the latency difference point. This positive deflection should then be observed with all
between the two muscles. The same stimulation site is used for CMAP's from proximal stimulation sites. Additionally, the sur
each recording. A supramaximal stimulus evokes a CMAP from face electrode located in the distal forearm is subject to record
each muscle and the onset latency from the abductor digiti ing volume-conducted potentials from a different set of
minimi muscle is subtracted from the onset latency to the first radial-innervated muscles as the stimulus site progresses more
dorsal interosseous muscle. A two-channel recording is helpful proximally. This is unlike the median and ulnar nerves where
because fewer stimuli are required. the hand intrinsic muscles are relatively isolated from the fore
Instrumentation Parameters. These data were not speci arm muscles and somewhat less prone to detecting volume-con
fied in the original study. However, as long as the same parame ducted electrical activity.
ters are used for both latencies the same time difference should £-1. The central core of a standard concentric needle elec
apply. Similar instrumentation parameters to those used for the trode serves as E-I for recording the radial nerve CMAP. This
median nerve are recommended. needle electrode is inserted into the extensor indicis proprius
Reference Values. The difference between the two onset la muscle by measuring approximately 4 cm proximal to the ulnar
tencies should not exceed 2.0 ms. Additionally, when this tech styloid and 1 or 2 cm toward the radius, Le., just lateral to the
nique is applied bilaterally, the time difference between the tendon of the extensor carpi ulnans muscle. 159 The patient is re
left/right first dorsal interossei's onset latencies should not quested to repeatedly extend and relax the second digit while
exceed 1.3 ms (Table 5-6).250 A time difference exceeding those the examiner palpates for muscle contraction. 159,334 A monopolar
noted above suggests that the deep branch of the ulnar nerve needle electrode also may be used,IS3
displaying the prolonged conduction time is compromised distal £-2. If a standard concentric needle electrode is used, the
to the innervation of the hypothenar muscles. needle's cannula serves as E-2. Should a monopolar needle
In the authors' opinion, the latency between these two mus serve as E-I, a surface E-2 may be located on the fifth metacar
cles is usually normal even in persons with lesions. The major pophalangeal joint. 183
ity of canal of Guyon lesions examined by the authors have Stimulation. The radial nerve may be excited in several lo
been a result of a ganglion cyst and produced primarily axonal cations. For the technique described in this text, a needle electrode
Chapter 5 NERVE CONDUCTION STUDIES - 199
is used for stimulation purposes. At each designated stimulation filter approximating 10 Hz and a high-frequency filter in the
site a monopolar needle can be used as the cathode, and a sur range of 10 kHz should suffice.
face anode located at a convenient site near the cathode. The Reference Values. The reference data provided are applica
original description of the technique used a monopolar needle ble only when recording with intramuscular needle electrodes
with 3 mm of Teflon removed from the tip. A pulse duration of (Table 5_7).334 The amplitudes are measured peak-to-peak.
0.2 ms at an intensity of 2-4 rnA was used. It is also possible to Onset latencies are to the initial deflection of the recorded re
use a standard monopolar needle, but reduce the pulse duration sponse irrespective of its polarity.
to 0.05 ms. 260 Slightly different currents may be necessary as a
reduced stimulus duration is delivered to the nerve. Whenever a Radial Nerve: Proximal Segment
needle electrode is chosen as the cathode, one optimally posi The radial nerve is the continuation of the posterior cord and
tions the electrode by delivering a stimulus that is supramaxi is the largest branch of the brachial plexus. Nerve fibers origi
mal but with the smallest current required to achieved the result. nating from cervical segments C5-C8 and possibly from T1
This is accomplished by moving the needle in small increments comprise this peripheral nerve. 144.324 All extensor muscles of the
with each pulse delivery to ensure near-nerve placement, i.e., a arm and forearm are innervated by the radial nerve. In the axilla
supramaximal response with the minimal amount of current and proximal portion of the arm, several branches are given off
necessary. the main radial nerve trunk to innervate the various heads of the
The first stimulus site is in the forearm 8 cm proximal to the triceps muscle. 324 Examination of conduction in the radial
ulnar styloid just lateral to the extensor carpi ulnaris muscle. nerve's distal segment has been described previously; however,
The radial nerve is subcutaneous for approximately 5 cm at this in this section we examine conduction from Erb's point to the
region and should be excited easily. 159 A second stimulus loca triceps muscle, i.e., exclusively the proximal neural segment of
tion for the radial nerve is at the elbow region in the groove the radial nerve to the triceps muscle.
formed by the lateral margin of the biceps brachii tendon and Recording Electrodes. Because the triceps muscle does not
the medial border of the brachioradialis muscle 6 cm proximal have a well defined motor point as detected by surface record
to the lateral epicondyle. Radial nerve excitation is also per ing electrodes. a standard concentric or monopolar needle elec
formed in the axillary region in the depression formed by the trode is preferred for recording.
coracobrachialis and medial border of the triceps muscles. E-1. The needle electrode is located deep within the sub
When performing stimulation at these three sites it is impera stance of the triceps muscle. Three mean distances are examined
tive that the same CMAP be obtained for each neural location from Erb's point as measured with obstetric calipers to assist in
to ensure that the recording electrode did not move signifi the examination of persons with different arm lengths. These dis
cantly. The above three stimulus locations allow the practi tances are: 21.5 cm, 26.5 em, and 31.5 cm (Table 5-7).105
tioner to examine two separate segments of the radial nerve, E-2. The standard concentric needle electrode's cannula
Le., arm and forearm. Surface stimulation may replace needle serves as the E-2 electrode, while a nearby surface electrode
excitation; however, a longer pulse duration approximating 0.5 functions as E-2 in surface or monopolar needle recordings.
ms may be necessary as the radial nerve is commonly sur Stimulation. A surface cathode and anode are located at
rounded by significant muscle and adipose tissues. A fourth Erb's point. The pulse duration should be between 0.5 and 1.0
stimulus location can be performed at Erb's point. Erb's point ms with an intensity capable of producing a supramaximaI re
is just lateral to the insertion of the sternocleidomastoid muscle sponse. Firm pressure applied at Erb's point is often necessary
and a few centimeters superior to the clavicle, i.e., supraclavic to evoke an optimal response.
ular fossa. Surface stimulation should only be attempted in this Instrumentation Parameters. A sweep speed of 2 ms/div
region to avoid pneumothorax induction from a needle cath and sensitivity capable of displaying the entire response on the
ode. A pulse duration of 0.5 or 1.0 ms may be necessary to screen are sufficient to obtain the desired responses. Also, low
completely activate the posterior cord from which the radial and high-frequency filters of less than 10Hz and greater than or
nerve arises. Firm pressure on the stimulator is typically neces equal to 8 kHz, respectively, are employed.
sary to ensure that the cathode and anode are as close to the
brachial plexus as possible. Radial Nerve: Motor
Table 5-7.
Instrumentation Parameters. When measuring the dis
tance across the brachial plexus (Erb's point to axilla) or arm DML NCV Amplitude Distance
segment (axilla to elbow) the use of obstetric calipers is recom (ms) (mls) (mY) (cm)
mended to more accurately reflect the distance traversed by the Segment
nerve.I60.193.334 Recall that the radial nerve does not pursue a
straight course in the arm but passes posterior to the humerus in Erb's-Axilla 72 ± 6.3
the spiral groove. About 10° of arm abduction may assist in ex Axilla-Elbow 69 ± 5.6 II ± 7.0 15.7:1: 3.3
amining the proximal segment of the radial nerve. Optimally,
Elbow-Forearm 62:1:5.1 13 ±8.2 18.1 ± 1.5
the forearm is fully pronated and the elbow should not be flexed
more than 10° or 15°.159 Because a needle electrode is located Forearm-EIP 2.4 ± 0.5 14±8.8 6.2 ± 0.9
within the muscle tissue, a rather large response can be expected Erb's-Triceps 4.5 ±O.I 20-30
that requires a sensitivity of about 5 m VIdiv. It is important to 4.9:1:0.1 25-28
emphasize that the amplitude as recorded with needle electrodes 5.3 ± 0.12 30-33
is of limited diagnostic value with respect to assessing axonal
loss or conduction block because the entire muscle is not evalu Filter setting are not specified but those approximating a low filter of 10Hz
and a high filter of 10kHz should suffice. Erb's data from Jebsen,ls9.160 remainder
ated. Sweep speeds of either 2 or 5 ms/div are appropriate de from Trojaborg and Sindrup.lOs.m Amplitudes are measured peak-to-peak and
pending upon the length of the subject's arm. Filter settings onset latencies to the recorded potential's initial deflection. Performed with in
were not provided in the quoted study; however, a low-frequency tramuscular needle recordings.
200 - PART II BASIC AND ADVANCED TECHNIQUES
Reference Values. The onset latencies to the initial deflec medial 1-2 cm of the thenar eminence is supplied by this
tion of the recorded response are documented for the above nerve. S! A lateral branch of this nerve also innervates the proxi
noted three distances (Table 5-7) .105 mal and lateral hypothenar eminence. The remainder of the
hand and digits are innervated by the terminal sensory branches
Phrenic Nerve of the median nerve distal to the carpal tunnel. Additionally, the
The phrenic nerve is a branch of the cervical plexus com distal two-thirds of the dorsal aspect of the first three and one
posed of fibers originating from the anterior primary rami of half digits are also supplied by the cutaneous braches of the
C3/C4/C5 with occasional contribution from C2 or C6. 144 In the median nerve.
cervical region, the nerve courses medially, anterior to the ante
rior scalene muscle to lie posterior to the sternocleidomastoid Antidromic Techniques
muscle. Once it enters the thoracic cavity, the phrenic nerve As previously defined, antidromic refers to the direction of
travels between the pericardium and pleura of the mediastinum. induced impulse propagation with respect to the recording elec
The nerve then pierces the diaphragm to innervate this muscle. trodes and the direction of naturally elicited action potential
One may wish to examine this nerve in persons suspected of propagation. In this section, antidromic implies that E-l is lo
having traumatic or acquired damage to the phrenic nerve. cated distal to the cathode. The action potential generated be
Recording Electrodes. There are several techniques for neath the cathode, therefore, is recorded at a more distal
recording the CMAP from the phrenic nerve.59.m.2l3 One can location. Physiologically, however, an action potential induced
locate the recording electrodes laterally over the ribs in the mid by natural stimuli would have propagated from the recording
axillary line or centrally over the xyphoid process. Our pre electrodes to the cathode. In this sense, the recording is per
ferred technique is placement of the active electrode proximal formed such that the induced action potential travels in the op
to the xyphoid process. 20.42 The patient should be supine without posite direction (anti) to what it would naturally take.
a pillow supporting the head. Both wrist and mid-palm antidromic stimulation techniques
E- J. A surface E-l electrode is secured 5 cm proximal to the are described. It has been suggested that in median nerve en
xyphoid process following appropriate preparation of the skin. trapment at the wrist, selectively examining median nerve sen
This location suffices for both left- and right-sided phrenic sory conduction across the transverse carpal ligament increases
nerve excitation. As a surface recording is used, the recorded the diagnostic sensitivity of neural conduction. 155.362 Although
CMAP yields a response appropriate for side-to-side amplitude the original study examined subjects' third digit, it is reasonable
comparisons. to assume that the same technique also can be applied to the
E-2. The surface E-2 recording electrode is best located ipsi second digit.
lateral to the side of stimulation at the costal margin approxi Digits II and III. The straight anatomic course of the
mately 16 cm distal to the E-l electrode. median nerve's sensory fibers from the wrist to the second and
Stimulation. A surface stimulator is located just posterior to third digits allows one to easily study sensory conduction. 164
the posterior border of the sternocleidomastoid muscle at the Either the second or third digit can be used for investigating the
level ofthe cricoid cartilage or just above the clavicle. 20•59 It is median nerve's SNAP. As previously noted for motor fibers, we
not uncommon with this placement to concomitantly excite the prefer techniques that use standard distances to those employ
brachial plexus. If this occurs, the stimulator should be reposi ing anatomical landmarks. Although there are multiple investi
tioned until the patient describes a hiccup-like sensation and an gations examining median nerve sensory conduction, very few
abdominal pulsation may be palpated. 216 investigators standardize the distance over which the nerve is
Instrumentation Parameters. See radial nerve stimulation. recorded.
Reference Values. Mean onset latencies for the CAMP are Recording Electrodes. Ring or clip electrodes are secured
6.54 ± 0.77 ms (5.5-8.4 ms) with base-to-peak amplitudes of to the fingers and used for both E-I and E-2. Several technical
660 ± 201 flV (301-1198flV).42 comments are relevant to the application of the ring recording
electrodes. It is preferable to rotate the electrodes a small
UPPER LIMB SENSORY NERVE CONDUCTION STUDIES amount while at the same time applying pressure prior to finally
securing the electrodes to the digit to help reduce the skin's im
The more common sensory nerve conduction techniques of pedance. A small amount of electrolyte gel is then placed along
the major sensory nerves in the upper limb are described. Both the ring electrode and it is again slightly rotated to ensure an
orthodromic and antidromic methods of eliciting SNAPs are equal amount of recording gel around the circumference of the
presented. We do not subscribe to the philosophy that an electrode. The open portion of the ring electrode should be pos
tidromic studies are somehow inferior to orthodromic studies terior, thus maximizing contact between the active recording
because of an occasional motor artifact possibly interfering with surface and the median nerve. A piece of tissue paper should
the SNAP. Anyone attempting to practice electrodiagnostic separate the ring electrodes from the adjacent digits to minimize
medicine should be familiar with both methods of examining movement artifact secondary to the electrodes contacting other
peripheral sensory nerves to be able to use an alternative tech fingers following stimulation.
nique when a given one yields less than optimal results. E-1. The E-l ring electrode is secured to either the second or
third digit as noted above (Fig. 5-21). The actual placement
Median Nerve should be 1-2 em distal to the metacarpophalangeal joint to
The median nerve provides cutaneous sensibility to the lat minimize volume-conducted motor responses from the acti
eral aspects of the palm as well as to the volar areas of the first vated hand intrinsic muscles.
three and one-half digits. 144,206 The first cutaneous branch of the E-2. An E-2 ring electrode should be positioned 4 cm or
median nerve is the palmar cutaneous branch of the median more distal to E-l to avoid amplitude reduction and latency
nerve. This nerve innervates the skin just distal to the distal shortening secondary to differential amplification effects of
wrist crease for a distance of several centimeters. Only the common mode signals being recorded (Fig. 5_22).78.79.80
Chapter 5 NERVE CONDUCTION STUDIES - 20 I
A B
E-2
E-2
Figure 5·22. Diagrammatic representation of electrode placement for antidromic median and ulnar nerve sensory conduction
studies. A, for median nerve examination the E-I recording electrode is located on the second or third digit just distal to the metacarpopha
langeal joint region and the E-2 electrode is placed at least 4 cm more distal on the respective digit. The median nerve is excited 7 cm (52) and 14
cm (51) proximal to E-I betWeen the tendons of the FCR and PL. B, With ulnar nerve studies, the E-I is positioned on the fifth digit just distal to
the metacarpophalangeal joint with the E-2 electrode as far distal as possible. Stimulation (S) of the ulnar nerve is performed 14 cm proximal and
medial to the tendon of the FCU.
Ground. As for motor studies, the ground electrode should SNAP as it occurs within several milliseconds of the stimulus
always be located between E-l and the cathode, preferably ad artifact. The relatively small size of the SNAP requires an am
jacent to E-l. This is the assumed position for all remaining sen plifier sensitivity of 10-20 j.l.V/div. OccaSionally, an exception
sory studies noted in this text. Alternatively, placing the ground ally large SNAP may require a sensitivity of 50 j.l.V/div. Filter
on the dorsum of the hand is acceptable, provided stimulus arti settings approximating 20 Hz to 2 kHz should yield clearly re
fact is minimal. producible SNAPs.
Stimulation. The median nerve is easily excited at the wrist Reference Values. Distal sensory latencies were recorded to
14 cm proximal to E-l measured on a straight line. The cathode the peak of the negative deflection or the onset latency of the
is positioned between the tendons of the flexor carpi radialis lat initial deflection while amplitudes are calculated from the ini
erally and the palmaris longus muscles medially. A pulse dura tial deflection to the major negative spike (Table 5-8). Negative
tion of 0.1-0.2 ms using a supramaximal current intensity is spike durations were also noted. The mid-palm temperature for
necessary. The anode is located proximal to the cathode. In this the data reported exceeded 31°C.
arrangement, the cathode is directly opposite E-l on a 14 cm
line between E-l on the digit and the cathode proximally. "Inching Technique"
Should a mid-palmar stimulation be necessary, the cathode is Both orthodromic and antidromic sensory studies clearly
located 7 em proximal to E-! (anode proximal) (Fig. 5-22). This demonstrate that there is often focal slowing across the trans
stimulation site optimally falls in the mid-palm region. If the verse carpal ligament in the carpal tunnel syndrome.31.S7.179.362 A
actual measured distance of 7 cm places the cathode near the technique exciting median nerve sensory fibers in I-em incre
distal aspect of the transverse carpal ligament, the recording ments across the wrist and into the hand while recording from
electrodes should be repositioned to a more distal location thus the second digit is described, i.e., short-segment stimulation. ISO
localizing the mid-palm stimulation more toward the middle of The intent of this type of stimulation is to localize an area of
the palm. The antidromic technique quoted used a needle cath nerve that displays focal slowing thus suggesting a correlation
ode, but the authors have used a surface cathode with little diffi
CUlty. When stimulating in the mid-palm with a surface cathode,
the pulse duration may need to be increased slightly above that Table 5-8. Median Nerve: Sensory
used at the wrist because of subcutaneous tissue thickness in OL (ms)",·I64 PL (ms)49.164 Amplitude (j.I.V)"'»4 Duration (ms)49
most persons' palmar regions. Care must be exercised to not el Antidromic
evate the pulse duration too much, otherwise a more distal site 2,4 ± 0.3 3.0 ± 0.3 10-90 1.2-2.4
of excitation than anticipated may occur. The use of a needle
monopolar cathode obviates the concern for crossing the palm's Orthodromic
impedance barrier and a pulse duration of 0.05 ms typically suf 2A ± 0.3 3.0 ± 0.3 15-50
fices for generating a supramaximal response. A surface anode, Antidromic: mid-palm to 14 em162
ring electrode, located on the thumb or preferably a dispersive Mid-palm 1.6 ± 0.2 67 ± 20 1.0 ± 0.1
electrode on the dorsum of the wrist yields good results with the 14 em 3.1 ± 0.2 52 ± 13 1.1 ± 0.1
above-noted needle cathode. PfW 52 ±4% 128 ± 29%
Instrumentation Parameters. A sweep speed of I or 2 OL. onset latency; PL. peak latency; PfW. palm to wrist ratio for latency and
ms/div is recommended to optimally resolve the recorded amplitude.
202 - PART II BASIC AND ADVANCED TECHNIQUES
between an anatomic site of neural compromise and an electro or distal wrist crease for a total of 12 points of neural excita
physiologic conduction abnormality. Although the method se tion. At approximately 3 cm distal to the zero reference, the
quentially stimulates the median nerve in I-cm increments, this distal edge of the transverse carpal ligment is believed to be
study is commonly known as the "inching technique."235 present. 168.180
Recording Electrodes. As this is an antidromic technique, An important cautionary note is necessary with respect to this
recordings are performed on digital sensory nerves distal to the technique. Because the median nerve passes beneath the trans
site of stimulation. Although the original method described verse carpal ligament and then into the palm under rather thick
recordings from the second digit, the same data most likely tissues, there is a varying depth of this nerve below the skin sur
apply to the third digit as well. face along its course.275 It is often necessary to use different cur
E-1. A ring E-l recording electrode is located on the second or rent intensities and pulse widths to obtain supramaximal
third digit just distal to the metacarpophalangeal joint (Fig. 5-23). responses. There is a danger that in some persons, particularly
E-2. The E-2 electrode is positioned distal to E-l at a distance individuals with rather calloused hands, excessive current may
approximating 4 cm if possible. Because this technique is pri be required to maximally excite the median nerve in or about
marily concerned with comparative latencies and possibly am the carpal tunnel region or mid-palm. There is a possibility,
plitudes over short segments, absolute times and distances are of therefore, of stimulus spread exciting the nerve slightly more
less importance than for the previously described investigation. distally than anticipated, thus producing a region of "abnormal"
Stimulation. The stimulation sites were determined by first segmentallatencies. 180,354 Judicious use of current intensity to
localizing the distal wrist crease, which is designated the zero induce supramaximal responses in this technique, particularly
or reference mark (Fig. 5-23). The distal wrist crease approxi by the beginning practitioner who has not had much practice, is
mates the proximal edge of the transverse carpalligament. 275 A mandatory with this method of short-segment stimulation.
line overlying the median nerve, between the tendons of the Alternatively, a needle cathode can be used.
flexor carpi radialis and palmaris longus muscles proximally, Instrumentation Parameters. An amplifier sensitivity of
and the third digit distally, serves as the referential measuring 10-50 ,..tV/div and a sweep speed of 1 or 2 ms/div should result
line. Six proximal and 5 distal stimulation sites are designated in clearly defined SNAPs. Filter settings of 20 Hz to 2 kHz were
with respect to the reference line where it crosses the zero line used in the original study; however, high and low filter settings
Figure 5·23. "Inching" technique. Sensory "inching" stimulation of the median nerve can be performed with recording electrode placement
as previously described for the median nerve. The ensuing antidromic median nerve SNAPs are shown and correspond to the various stimulation
sites (horizontal lines across the palm of the hand). (From Kimura J:The carpal tunnel syndrome: Localization of conduction abnormalities within
the distal segment of the median nerve. Brain 1979; 102:619--635, with permission.)
Chapter 5 NERVE CONDUCTION STUDIES - 203
approximating these values are acceptable as comparative laten used for more proximal segments. The reason the antidromic
cies are the important parameters of interest. SNAP amplitudes are comparatively larger is because the
Reference Values. The SNAP's onset is recorded for each recording electrodes are located over the digits where the nerve
stimulus site, and the latency difference between adjacent fibers are subcutaneous and relatively close to the electrodes. In
neural excitation points is calculated. Should the onset latency orthodromic techniques, the nerve is usually deeper in the limb
be difficult to detect, one can also use the negative peak latency and subsequently farther from the recording electrodes, thus
to determine segmental conduction times. Normal sensory generating smaller amplitude responses. Orthodromic SNAPs,
axons demonstrate a segmental latency shift between 0.16 and because of their small amplitude, may be difficult to observe at
0.21 ms.180.183 Short-segment latency shifts exceeding these increasing distances from the stimulus site, e.g., when attempt
limits may be abnormal and indicate focal slowing of neural ing to calculate conduction velocities over several segments. It
conduction. Again, caution must be exercised not to use too has been recommended that needle recordings be used for or
much current and produce an erroneous segmental latency shift. thodromic studies; however, care must be exercised in near
These reference values were obtained in forearms maintained at nerve recordings. The amplitude of the recorded response is
or above 34°C with infrared heating lamps. very dependent upon the distance between the nerve and needle.
Failure to ensure a near-nerve placement at consecutive sites
Orthodromic Technique may cause one to erroneously conclude that pathology has
When performing orthodromic techniques, the median caused a comparative amplitude reduction when indeed it is a
nerve's sensory fibers in the digits are excited and the ensuing result of poor needle placement. This is particularly a problem
response is recorded at the wrist. This type of stimulation and when inexperienced examiners are following patients serially
recording is referred to as orthodromic because the induced and attempting to compare amplitudes with those previously
neural impulse propagates in the same direction as a sensory obtained, especially by a different examiner.
action potential generated by natural stimuli. Additionally, the Early studies investigating both antidromic and orthodromic
response is recorded proximal to where it is produced. In this SNAPs concluded that there was no significant difference be
way, the sensory action potential travels centripetally, Le., phys tween the two techniques with respect to latency as measured to
iologically toward the central nervous system. the potential's peak or onset.30.233.234 Later studies concluded that
Recording Electrodes. The recording electrodes are typi orthodromic median nerve studies resulted in potential latencies
cally positioned over the median nerve at the wrist. This is the significantly shorter than those obtained with antidromic tech
same general location as previously described for cathodal niques.47.326 The implication was that there is some type of poorly
placement in antidromic excitation of the median nerve. understood physiologic explanation for the way in which nerves
E-1. A surface electrode is situated over the median nerve conducted impulses in an antidromic compared to orthodromic
between the tendons of the flexor carpi radialis and palmaris manner. In reality, the difference is secondary to the technique
longus muscles. The distance between E-l and the cathode (see used to investigate neural conduction. The inter-electrode sepa
below) is standardized at 14 cm. 233 •234 ration for recording antidromic responses was 4 cm while that
E-2. Placement of the E-2 recording electrode is crucial (see used for orthrodromic studies was less. Reducing the inter-elec
below: antidromic vs. orthodromic conduction). It is recom trode separation tends to reduce the recorded potential's ampli
mended to use separate surface disc electrodes for an inter-elec tude and latency.7&-go Using similar distances between E-l and
trode separation between E-I and E-2 of 4 cm.233,234 E-2 results in similar latencies for both antidromic and ortho
Stimulation. A ring electrode secured around the second or dromic responses.49 Thus, the original investigators were correct
third digit serves as the cathode while a second ring electrode in finding that nerves conduct the same whether propagating an
several centimeters more distal on the digit is the anode. The impulse orthodromically or antidromically.
placement is the same as that noted above for E-I and E-2, re
spectively, in antidromic sensory nerve recordings. An appro Ulnar Nerve
priate pulse duration and current intensity is used to produce a The ulnar nerve's cutaneous distribution innervates the
supramaximal SNAP. medial aspect of the volar and dorsal regions of the hand not
Instrumentation Parameters. See antidromic median nerve supplied by the median or radial nerves. l44 Approximately 10
instrumentation parameters. cm proximal to the ulnar styloid, the first cutaneous branch of
Reference Values. Peak and onset latencies have been the ulnar nerve, the palmar ulnar cutaneous nerve, becomes
recorded for temperature and distance controlled orthodromic distinct and travels distally to innervate a small patch of skin on
investigations of the median nerve (Table 5-8). The reference the proximal hypothenar eminence.324 This nerve is somewhat
data vary depending on the inter-electrode separation between inconstant and is often replaced by terminal sensory ulnar nerve
E-l and E-2 (see below). fibers. Just distal to the origin of the palmar cutaneous branch of
the ulnar nerve a second cutaneous nerve, the dorsal ulnar cu
Antidromic vs Orthodromic taneous nerve, arises to supply the dorsum of the hand.
Although one may read that antidromic studies are prone to Specifically, the skin overlying the medial two metacarpal
volume-conducted muscle responses contaminating the SNAP bones is innervated by this nerve. Within the hand, the ulnar
under investigation,58.312 this criticism is infrequently of clinical nerve divides into the superficial and deep ulnar nerves. The su
significance. Locating the recording ring electrodes just distal perficial branch of the ulnar nerve innervates the hypothenar
to the metacarpophalangeal joint significantly reduces concomi eminence and provides several superficial terminal branches to
tant overlap of motor and sensory responses.217 Additionally, innervate the fifth and medial one-half of the fourth digits.
asking the patient to abduct the fingers during neural activation These superficial terminal branches also innervate the dorsal
can help minimize any contaminating motor artifact. The ampli terminal portions of the above-noted digits. The dorsal ulnar cu
tude of antidromic responses is typically larger than those ob taneous nerve provides cutaneous sensibility to the proximal re
tained through orthodromic techniques, and therefore can be gions of the digits' dorsum similar to the radial nerve's function
204 - PART II BASIC AND ADVANCED TECHNIQUES
with respect to the median nerve and the lateral three and one then flexed as noted above. These two skin designations serve
half digits. as the two stimulation sites with the elbow flexed to 135°. A
As with the median nerve, a number of nerve conduction fourth stimulation location is delineated approximately 11 cm
techniques exist to investigate the integrity of the ulnar nerve's proximal to the above elbow site. The distance between the 3
sensory fibers. An attempt is made to only note the more popu segments is then measured. It is important to calculate the dis
lar techniques controlling for distance and temperature. The in tance across the elbow in the flexed position as previously'de
terested reader is encouraged to consult several nerve fined (see ulnar nerve motor section) by following the course of
conduction manuals for additional techniques. 64 •m As for the the ulnar nerve. Once can certainly use distances less than those
median nerve, both antidromic and orthodromic methods of in described; however, recall that as the segmental distance de
vestigating the superficial terminal branches of the ulnar nerve creases, the percent measurement error increases.
are described. Additionally, nerve conduction velocities across Instrumentation Parameters. Instrument parameters simi
the elbow segment are also described to allow the practitioner lar to those noted for the median nerve's sensory fibers are used.
the opportunity to investigate ulnar nerve sensory conduction Reference Values. Distal sensory latencies are measured to
across a common site of ulnar nerve entrapment. the peak of the negative deflection (Table 5-9). When comput
ing sensory nerve conduction velocities, however, the potential
Antidromic Technique is measured to the initial deflection of the negative peak where
Recording Electrodes. The general comments regarding the waveform departs the baseline.
ring electrode application noted for median nerve sensory stud
ies also apply for ulnar nerve sensory investigations. Orthodromic Technique
E-J. The E-I recording electrode is located on the fifth digit The orthodromic technique for evaluating the ulnar nerve is
just distal to the metacarpophalangeal joint or midway along the essentially the same as that used for the median nerve.
proximal phalanx (Fig. 5-22). If motor artifact is encountered, Essentially, the E-I and E-2 ring recording electrodes are now
positioning the electrode slightly more distally may help, and used as the cathode and anode, respectively. The recording elec
asking the patient to abduct the digits can also be of assistance trodes become separate disc electrodes located on the ulnar
in some persons. nerve just lateral to the tendon of the flexor carpi ulnaris muscle
E-2. One should attempt to locate E-2 as distal on the fifth 14 cm proximal to the cathode. A supramaximal stimulus is ap
digit as possible to maximize the amplitude of the SNAP. In plied to the fifth digit. The orthodromic SNAP's latency is
other words, the optimal separation of 4 cm is preferable, but recorded to the peak while the amplitude is calculated from the
the length of the fifth digit may preclude achieving this goal. initial deflection to the negative peak (Table 5-9).
Stimulation. The ulnar nerve is stimulated with a surface
cathode 14 cm proximal to the E-l recording electrode. The Dorsal Ulnar Cutaneous Nerve
actual location of the cathode is just lateral to the tendon of the Recording Electrodes. Separate disc recording electrodes
flexor carpi ulnaris muscle (forearm supinated). The anode is are located on the hand's dorsum. Because the dorsal ulnar cuta
always positioned proximal to the cathode. neous nerve and its parent mixed nerve are in close proximity, it
When attempting to compute sensory conduction velocities is difficult to avoid concomitantly exciting both nerves. This
for various segments of the ulnar nerve, the same proximal stim simultaneous neural excitation results in the SNAP closely
ulation sites for motor studies are used. Specifically, the elbow
is flexed 135" and supinated. Again, the arm is abducted ap
proximately 90° and is rested on the same pillow supporting the
patient's head. This position clearly exposes all sites to be stim
ulated. Although the original investigation excited the ulnar
nerve digitally at 11 cm, a 14-cm distal excitation should not
alter the nerve conduction velocities for the arm, across-elbow,
and forearm regions. With the elbow first extended, a mark on
the patient's skin is made 4 cm distal to the medial epicondyle
and approximately 10 cm proximal to this site. The elbow is
E-2. The E-2 recording electrode is also a ring electrode sim roots supplying this nerve originate from C5IC6. 144 The nerve
ilar to that for E-l and is located distally on the first digit near becomes rather superficial at the lateral margin of the biceps
the base of the thumbnail. It is important to place a tissue or dry brachii tendon and forms two branches. An anterior branch pro
gauze pad between the thumb and remainder of the hand to min vides sensibility to the anterolateral aspect of the forearm proxi
imize movement artifact from the rings brushing against the mal to the wrist. A dorsal branch innervates the skin on the
palm of the hand. dorsolateral forearm. Although it is possible to examine this
Stimulation. A surface cathode can be located on the lateral nerve with an orthodromic needle technique,m an antidromic
margin of the radius 14, 16, and 18 cm proximal to E-l. The surface recording and stimulation method is described as it is
wrist is in neutral position and the thumb adducted for measur considerably easier to perform. 307
ing the above-noted distances. Recording Electrodes. Unlike a number of the previously
Instrumentation Parameters. See previously described su described studies, this method uses a plastic bar with embedded
perficial radial technique. disc electrodes 3 cm apart in order to reproduce the original
Reference Values. The methods used to calculate latencies technique. This allows one to use the reported reference data.
and amplitudes are the same as those previously described for Should one wish to use separate disc electrodes at more than 3
recordings at the wrist (Table 5-10). cm separation, slightly longer peak latencies and larger ampli
tudes can be anticipated. As always, if the original method is
Lateral Antebrachial Cutaneous Nerve modified, new reference data must be developed.
The lateral antebrachial cutaneous nerve is the cutaneous sen E-l. A line is constructed connecting a site just lateral to the
sory termination of the musculocutaneous nerve. The nerve biceps brachii tendon at the antecubital fossa and the radial
pulse at the wrist (Fig. 5-26). At 12 cm distal to the antecubital
location, the E-l electrode is secured to the forearm. 307
E-2. The E-2 electrode embedded in the plastic bar is posi
tioned on this same line distal to E-I. If a separate surface elec
trode is used, care should be taken to align both E-l and E-2 on
the above-noted line.
Stimulation. The surface cathode is located at the above
noted site just lateral to the biceps brachii tendon (Fig. 5-26).
For this technique it is crucial to have firm pressure applied to
the stimulator to position the cathode deep enough into the
arm's soft tissues and ensure close proximity to the nerve.
Should this response not be readily detected, the E-l and E-2
electrodes should be repositioned slightly prior to concluding
the response is pathologically absent. A normal contralateral
(unaffected) response helps implicate a pathologic process
rather than poor technique. The current intensity is best deliv
ered in small increments to preferentially activate the sensory
fibers of the lateral antebrachial cutaneous nerve. Too strong an
excitation pulse may coactivate the nearby median nerve with
volume-conducted potentials, overwhelming the small sensory
response.
Instrumentation Parameters. See median nerve sensory
technique.
Reference Values. Although temperature was not recorded,
the forearm should be subject to less temperature variation than
that encountered in the digits. The SNAP's onset latency was
1.8 ± 0.1 ms (1.6-2.1 ms) and the peak latency was 2.3 ± 0.1 ms
(2.2-2.6 ms).3()7 Conduction velocities using onset latencies
were 65 ± 3.6 mls (57-75 mls) and amplitudes were 24 ± 7.2
j.LV (12-50 j.LV). Left/right latency differences for both onset
and peak were 0.1 ± 0.1 ms (0.0--0.3 ms).
MEDIAL ANTEBRACHIAL CUTANEOUS NERVE
The medial antebrachial cutaneous nerve originates from the
medial cord or rarely the lower trunk, and is derived from seg
ments C8 and Tl.226.265 This nerve is subcutaneous just proximal
to the medial epicondyle and course along the medial aspect of
the arm to provide cutaneous sensation to the medial forearm.
Figure 5-26. Lateral antebrachial cutaneous nerve. When ex Recording Electrodes. As for the lateral antebrachial cuta
amining the lateral antebrachial cutaneous nerve the E-I (R.) elec neous nerve, disc electrodes embedded in a plastic bar are used.
trode is located distal to the biceps tendon (see text) while the E-2 E-l. The medial epicondyle is palpated with a line con
electrode (Rr) is situated distal to E·I. The nerve is excited just lateral structed between the medial epicondyle and ulnar styloid. The
to the biceps brachii tendon. (From Ma OM, lives on JA: Nerve E-I electrode is placed on this line 8 cm distal to the medial epi
Conduction Handbook. Philadelphia. F.A. Davis, 1983, with permission.) condyle (Fig. 5-27).
Chapter 5 NERVE CONDUCTION STUDIES - 207
Median/Radial Nerves to Digit I palmaris longus muscles. The location for the cathode is deter
As previously stated, the median and radial nerves supply the mined by measuring from E-1 to the center of the distal wrist
cutaneous innervation to the first digit. By applying electrodes crease and then proximally until 10 cm is reached. By moving
to the thumb, one can perform either orthodromic or antidromic the cathode on a line halfway between the median and radial ex
evaluations of both cutaneous nerves. Antidromic studies are citation sites, it is possible to coactivate both median and radial
preferred because they yield larger and more easily recorded nerves. This last method of stimulation is not recommended for
SNAPs.37.261.298 attempting to detect pathology.
Recording Electrodes. Ring electrodes are used to record Instrumentation Parameters. See median nerve sensory
the two nerves' SNAPs. The region of noncontact for the ring parameters.
electrodes should be the medial aspect of the thumb (hand Reference Values. When coactivating both median and su
supinated). This electrode position assists in recording the po perficial radial nerves, a characteristic pair of potentials is ob
tential from both nerves. served. Normally, either one fused response is noted or there is
£-1. The E-l ring electrode is secured to the base of the first less than a 0.5 ms difference between the two potentials' peaks
digit approximating the metacarpophalangeal joint (Fig. 5-28). (Table 5-11 ).167.260 A prolongation of one of the peaks in re
This location is similar to that noted for recording the superfi sponse to individual or dual nerve excitation more than 0.5 ms
cial radial nerve response from the thumb. 2lS suggests entrapment. Stimulating each nerve singly at their op
£-2. A ring E-2 electrode is positioned distally on the thumb timal location defines which nerve is slowed. As the median
close to the base of the thumbnail. nerve is commonly entrapped at the wrist, it is more likely that a
Stimulation. There are three stimulation sites for this tech lesion affects this nerve.
nique. First, the superficial radial nerve is excited 10 cm proxi
mal to E-l on the lateral margin of the radius (Fig. 5-28). The Median/Ulnar Nerves to Digit IV
second site of stimulation is over the median nerve proximal to The fourth digit or "ring finger" is supplied on its volar sur
the wrist between the tendons of the flexor carpi radialis and face by the median nerve on its lateral aspect and ulnar nerve on
208 - PART II BASIC AND ADVANCED TECHNIQUES
Figure 5-29. Median/ulnar mixed nerve response. Location for stimulating and recording electrodes for performing a mixed nerve evalua
tion of the median (left) and ulnar (right) nerves. (From Stevens JC: The electrodiagnosis of carpal tunnel syndrome. Muscle Nerve 1987; I0:
99-113, with permission.)
the fourth and fifth digits (Fig. 5-29). Similar statements regard of most of the reported lower limb motor studies are referred to
ing stimulation of the median nerve are equally pertinent to the standard texts. 64 •216 Five NCS techniques (femoral, peroneal,
ulnar nerve. tibial, sciatic, and pudendal nerves) are described as these
Instrumentation Parameters. A sweep speed of 2 ms/div assess most of the lesions likely to be encountered even by ex
with an amplifier sensitivity of approximately 10-20 ~V/div aminers involved in a large practice.
should suffice for obtaining clearly defined responses. Filter set
tings approximating 10 Hz and 2 kHz are recommended. Femoral Nerve
Reference Values. Negative peak latencies for the median The femoral nerve is comprised of nerve fibers originating
nerve have a mean of 1.8 ± 0.02 ms with a range of 1.5-2.2 from the dorsal aspects of the lumbar ventral primary rami
ms.312 Peak-to-peak amplitudes are noted at 100 ± 5.l ~V with a L2-L4.144 It courses through the psoas muscle and lies be
range of 50-180 ~Y. The ulnar nerve has the same normal la neath the iliacus muscle. The iliacus muscle is innervated
tency parameters as the median nerve. The ulnar nerve's peak while the nerve is located within the abdominal cavity, and it
latency should not differ from the median response by more then enters the femoral triangle. The femoral nerve travels
than 0.2 ms. Amplitudes should exceed IS J..LY. Temperatures into the leg under the inguinal ligament approximately
measured over the first dorsal interosseous muscle are recom halfway between the anterior superior iliac spine and the
mended to be between 33-36°C. pubic tubercle. Once in the leg, the femoral nerve can be lo
cated proximally by palpating the femoral artery and sweep
ing 1 or 2 cm laterally. Roughly 4-5 cm distal to the inguinal
COMMON LOWER LIMB NERVE ligament, the femoral nerve divides into an anterior and pos
CONDUCTION STUDIES terior division. The anterior division innervates the skin over
the anterolateral thigh, and also supplies the pectineus and
There are a number of relatively easy-to-perform lower limb sartorius muscles. The posterior division innervates the hip
nerve conduction techniques. Essentially, the basic principles and knee joints and the quadriceps muscle and terminates as
applied to upper limb nerve conduction studies pertain to lower the saphenous nerve.
limb nerve conductions. NCVs for lower limb nerves are gener Recording Electrodes. Unless otherwise stated, all lower
ally slower than for upper limb nerve segments. It is particularly limb recordings are performed with surface electrodes. The ma
important to master a number of motor and sensory lower limb jority of motor evoked responses are of sufficient amplitude to
nerve conduction methods because the majority of generalized be easily detected with surface electrodes. Of course, in patho
processes affecting the peripheral nervous system begin in the logic situations, should a response not be observed with surface
distal aspects of the lower limb and progress proximally. As electrodes, one may wish to consider an intramuscular needle
with upper limb NCS, the techniques attempting to standardize recording to document that a response is still present. An NCV
nerve conduction methods for distance and temperature are can be obtained with this technique.
noted. E-1. An E-I recording electrode is located over the mid-por
tion or most prominent aspect of the vastus medialis muscle. If
LOWER LIMB MOTOR NERVE CONDUCTION STUDIES an initial positive deflection is observed with neural excitation,
E-I may need to be repositioned slightly in order to generate a
There are a number of lower limb motor nerve conduction negative deflection from the baseline.
studies commonly performed. Although it is impractical to at E-2. E-2 is most conveniently secured to the patella as this is
tempt a litany of every described technique for lower limb a relatively electrically silent region.
motor studies, those believed to be used most often in clinical Stimulation. Either a needle or surface stimulator may be
practice are detailed. Practitioners interested in a compendium used. Although a surface cathode/anode are convenient for the
210 - PART II BA51C AND ADVANCEDTECHNIQUE5
practitioner, the deep location of the nerve may require high intensity are optimized by adjusting both the needle's depth and
current intensities and pulse durations. This possibility can current delivered.
result in a rather uncomfortable examination for the patient. Three stimulation sites are recommended just as for upper
Should the patient have difficulty tolerating the stimulation, a limb nerve conduction studies: above and below the inguinal
needle cathode should be considered as less current intensity is ligament, and at Hunter's canal along the medial aspect of the
necessary because the cathode is positioned next to the femoral thigh. Again, the femoral artery is located in the inguinal region
nerve. In this instance, a surface or needle anode located several at a site 1-2 cm lateral to the femoral artery. The separation be
centimeters more proximally is used. As long as one is lateral to tween the two proximal cathodal stimulation points should ap
the femoral artery, there should be little danger of piercing the proximate 5-6 cm. The original description of this technique
artery provided the needle electrodes are perpendicular to the used a mean distance between stimulation locations of 5.5 ±
skin. Even though the nerve lies rather deep, the needle is ad 1.6 cm. The total length of the femoral nerve between the prox
vanced slowly delivering a stimulating pulse of moderate inten imal stimulation site and E-l was noted to be 35.4 ± 1.9
sity. As the muscle contraction increases, the current intensity is cm.64.165.216
reduced until a small amount of current produces a large Instrumentation Parameters. The instrument's sweep
quadriceps muscle contraction. The needle location and current speed and amplifier settings were not noted in the original study
describing the above noted technique. '65 However, a sweep
speed of 2 or 5 ms/div, amplifier gain of 2,000 to 5,000 J.lVIdiv
with filter settings approximating 10 Hz to 10 kHz result in
easily obtainable CMAPs. The same parameters can be used for
all lower limb studies.
Reference Values. The latencies from above and below the
inguinal ligament to E-l are 7.1 ± 0.7 ms (6.1-8.4 ms) and 6.0 ±
s, 0.7 ms (5.5-7.5 ms), respectively. 165 Conduction velocities from
above and below the inguinailigament to the mid-thigh location
are 66.7 ± 7.4 mls (50-96 mls) and 69.4 ± 9.2 mls (50-90 mls),
respectively. The time of conduction across the inguinalliga
ment region is 1.2 ± 0.4 ms (0.8-1.8 ms).
Sciatic Nerve
The sciatic nerve is the largest nerve in the human body and
formed by nerve fibers originating from lumbosacral segments
L4-S3. 144 The muscles innervated are the medial and lateral
hamstrings as well as all of the muscles distal to the knee joint.
The above-noted root levels fuse to form the sciatic nerve as it
travels along the posterior aspect of the pelvis to enter the
S2
tibial gluteal area through the greater sciatic foramen. Traveling deep
to the gluteus maximus muscle the sciatic nerve enters the lower
limb beneath the biceps femoris muscle. At about the mid-thigh
to distal one-third of the thigh, two major divisions of the sciatic
nerve, tibial and peroneal divisions, become physically distinct
as separate nerves. The tibial division of the sciatic nerve sup
plies the long head of the biceps femoris, semitendinosus, and
semimembranosus, as well as a portion of the adductor magnus
muscles. The peroneal division innervates the short head of the
biceps femoris. Distal to the knee all muscles are innervated
either by the tibial or peroneal nerves (see below).
This nerve may be injured by traumatic dislocations of the
hip, femur fractures, pelvic ring fractures, or by local injection
injuries. When called upon to examine the sciatic nerve for the
above or other causes, the described technique may be of some
assistance in determining neural injury.
Recording Elt.ctrodes. Surface or needle electrodes may be
used to record from either the tibial or peroneal component of
the sciatic nerve. Surface recordings may offer the advantage of
using the amplitudes for diagnostic purposes.
Figure 5-30. Sciatic nerve evaluation. The sciatic nerve is stimu E- 1 Tibial Component. An E-t electrode is located over the
lated at the gluteal fold (51) using a 7S-mm monopolar needle as the abductor hallucis muscle 1 em distal and 1 em inferior to the
cathode with a surface anode positioned nearby. The tibial and per navicular bone in the foot (Fig. 5-30).
oneal nerves can then be excited at the popliteal fossa (~. Recording E-1 Peroneal Component. The E-l recording electrode is sit
electrodes are positioned on the extensor digitorum brevis and ab uated over the main bulk of the extensor digitorum brevis
ductor hallucis for examining the peroneal and tibial portions of the muscle on the foot's dorsum (Fig. 5-30).
sciatic nerve, respectively. (From Ma DM, Liveson JA: Nerve E-2 Tibial Component. E-2 is located on the medial aspect of
Conduction Handbook. Philadelphia, F.A. Davis, t 983, with permission.) the foot at the first metatarsophalangeal joint.
Chapter 5 NERVE CONDUCTION STUDIES - 211
two terminal branches, one sensory and the other motor. The with manually pressing the cathode and anode into the depth
sensory nerve provides cutaneous sensibility to the area be of the tissue medial to the biceps femoris tendon and away
tween the first and second digits while the motor branch inner from the tibial nerve. Unfortunately this does not always pro
vates the extensor digitorum brevis. During the deep peroneal duce the desired results and it may be impossible to activate
nerve's course in the leg, the following muscles are innervated: just the peroneal nerve with a surface stimulator. An alterna
tibialis anterior, extensor digitorum longus, peroneus tertius, tive technique is to locate the stimulator's cathode/anodt;: on
and extensor hallucis longus. As one of the major nerves inner the lateral aspect of the thigh at the popliteal fossa level on the
vating the lower limb, it is important to be able to assess the per skin overlying the biceps femoris tendon. Some pressure in
oneal nerve electrophysiologically. The peroneal nerve may be combination with an increased pulse width may be required to
compromised in pelvic fractures, traumatic hip fractures and obtain a response. If both surface techniques fail, the practi
dislocations, femoral fractures, and entrapment or trauma at the tioner should consider a needle cathode. A current capable of
fibular head. exciting just the peroneal nerve is delivered after the needle
Recording Electrodes. There are two common recording has been positioned over the peroneal nerve. One must exer
techniques typically employed in assessing the integrity of the cise some caution and review the pertinent anatomy to avoid
peroneal nerve. Recordings can either be obtained from the ex puncturing the popliteal vessels.
tensor digitorum brevis (EDB) or tibialis anterior (TA) muscles.
Both methods are described as they are complementary in at Tibialis Anterior
tempting to define the level of possible neural compromise as E-1. The motor point of the TA is located by placing E-1 at
well as the extent of a lesion. the junction of the muscle's proximal one-third and distal two
thirds between the tibial tuberosity and prominence of the lat
Extensor Digitorum Brevis eral malleolus over the bulk of the muscle. 68
E-1. A surface E-l recording electrode is positioned over the E-2. An E-2 electrode is positioned over the medial aspect of
main bulk of the EDB muscle (Fig. 5_30).162.216 Occasionally, the tibia about the ankle.
slight repositioning of this electrode is required to obtain a Stimulation. Same as the two proximal stimulation sites
sharp initial negative deflection. noted above for EDB recordings.
E-2. The E-2 surface electrode is located on the fifth Instrumentation Parameters. A sweep speed of 5 ms/div,
metatarsophalangeal joint or on the fifth digit. sensitivity of 1,000 ~V1div, and filter settings approximating 10
Stimulation. In evaluating conduction for the deep peroneal Hz to 10 kHz is recommended when using the reference data
nerve with recordings obtained from the EDB, three stimula noted below. Less amplifier sensitivity than noted above is often
tion sites are suggested to evaluate both proximal and distal necessary to measure the potential's full amplitude.
nerve segments. Excitation of the peroneal nerve distally is car Reference Values. Distal motor latencies and conduction
ried out by locating the cathode just lateral to the TA tendon. velocities for the EDB and TA are provided (Table 5-12). Leg
Occasionally, the nerve may be rather deep beneath subcuta temperature at the recording sites should be monitored and
neous and tendo:lous tissues requiring an elevation in the stim maintained above 29-30°C.
ulus' pulse width. The second stimulus of the same pulse
duration is delivered to the peroneal nerve a few centimeters Tibial Nerve
distal to the fibular head. Finally, the peroneal nerve is excited The tibial nerve is the medial and larger portion of the sci
a third time in the popliteal fossa as the nerve courses medial to atic nerve arising from lumbosacral nerve fibers L4-S3. 144 At
the biceps femoris tendon. This last site of stimulation is some approximately the level of the popliteal fossa, the tibial por
what difficult and requires both patience and experience to se tion of the sciatic nerve becomes a distinct nerve trunk. All
lectively depolarize the peroneal nerve. This difficulty arises posterior compartment leg muscles and foot intrinsic muscles
because of the tibial nerve's close proximity. A stimulus deliv except the EDB are innervated by the tibial nerve. The nerve is
ered to the popliteal fossa frequently activates both the per superficial in two regions, at the popliteal fossa and posterior
oneal and tibial nerves. The distally located E-l electrode then to the medial malleolus. Traveling posterior to the flexor reti
detects the depolarization associated with both the EDB and in naculum at the ankle, tarsal tunnel, the tibial nerve enters the
trinsic foot muscle innervated by the tibial nerve. This situation foot to terminate as two separate nerves, I.e., the medial and
may be detected if the CMAP from the proximal stimulation lateral plantar nerves.
site does not appear similar to the response obtained at the Recording Electrodes. There are two sites from which to
ankle. It is obviously important to only excite the peroneal record a CMAP following tibial nerve stimulation. One can ex
nerve. This may be accomplished by using just the amount of amine conduction to not only the tibial nerve segment in the leg,
current necessary to stimulate the peroneal nerve combined but also the terminal portions of the medial and lateral plantar
nerves. Routine tibial nerve conductions are performed with
recordings to the abductor haUucis (AH) muscle, medial plantar
Table 5-12. Peroneal Nerve nerve, to assess conduction in the leg (Fig. 5-30).216 Should one
DML (ms) PNCV (m/s) AMP(mV) DNCV (m/s) AMP(mV)
desire information on the lateral plantar nerve, recordings can
be performed to the abductor digiti quinti pedis.
TA Recordingoa E-1: Medial Plantar Nerve. A surface E-I electrode is lo
3.0 ± 0.6 66.3 ± 12.9 3.9 ± 1.2 cated 1 cm posterior and inferior to the navicular tubercle on the
EDB Recordinglll· 162 medial aspect of the foot (Fig. 5-30).
4.5 ± 0.8 53.9 ± 4.3 4.4 ± 1.4 51.6 ± 4.1 5.0 ± 1.5 E-2: Medial Plantar Nerve. An E-2 electrode is secured to
DML. distal motor latency; PNCY, proximal NCV from popliteal fossa to fibular the metatarsophalangeal joint or distal aspect of the first digit.
head regions; AMP, amplitude of CMAP measured from baseline to negative E-1: Lateral Plantar Nerve. The E-l recording electrode is
peak; DNC¥, distal NCV for fibular head to ankle segment. positioned immediately inferior to the lateral malleolus halfway
Chapter 5 NERVE CONDUCTION STUDIES - 213
Table 5·13. Tibial Nerve medial and lateral plantar nerves. As with previously described
DML (ms)l02 AMP' (mV)I02.162 NCV '02 nerve conduction techniques, an effort is made to present only
the methods using standard distances, surface recordings, and
MPN (8 em)
temperature controls. It is not always possible to comply with
3.4 ±0.5 11.8 ± 4.5 8.8 ± 3.4 54.9 ± 7.6 these criteria, however, and the most reliable methods in the au
LPN (8 em) thors' experience are presented.
3.6 ± 0.5
MPN (10 em) Lateral Femoral Cutaneous Nerve
3.8 ± 0.5 7.54 (3.5-22) The lateral femoral cutaneous nerve is a pure sensory nerve
LPN (10 em)
formed from the ventral primary rami of nerve roots L2 and
3.9 ± 0.5 7.25 (3.0-10.0) L3. 144 This nerve is posterior to the psoas muscle and passes
from the lateral border of the psoas muscle to traverse the ilia
DM!... distal motor latency from cathode posterior to medial malleolus to E-I; cus muscle. It then enters a tunnel in the lateral aspect of the in
MPN, medial plantar nerve; LPN, lateral plantar nerve. AMP+, amplitude of
CMAP negative spike from distal stimulation;AMpt, amplitude of CMAP nega guinalligament. Distal to emerging from this tunnel the nerve
tive spike from proximal stimulation; NCY, NCV over leg segment from may pass over or through the sartorius muscle. The lateral
popliteal fossa to ankle region. MPN and LPN designate medial and lateral femoral cutaneous nerve divides into anterior and posterior
planter nerves, respectively. Table is incomplete because only data obtained branches to provide cutaneous sensation to the anterolateral
from studies using similar techniques have been included. DML'02;AMP'61.l5O;
AMP and NCV. 162
aspect of the thigh. Injury to this nerve typically leads to altered
sensation in its cutaneous distribution and is referred to as mer
algia paresthetica. 313
between the sole of the foot and the inferior tip of the lateral Recording Electrodes. Because of the rather small ampli
malleolus approximating the abductor digit quinti pedis' motor tude of most lower limb SNAPs, the skin beneath both E-] and
point. E-2 recording electrodes should be gently abraded to reduce the
£-2: Lateral Plantar Nerve. For the lateral plantar nerve an skin impedance. Also, the patient must be completely relaxed as
E-2 electrode is positioned over the fifth metatarsophalangeal motor artifact may interfere with detection of the desired re
joint or distal portion of the fifth digit. sponse. It is important to ensure that all electrodes are properly
Stimulation. The tibial nerve is routinely excited in two po secured to the optimal location as lower limb hair may result in
sitions. A stimulus in the popliteal fossa and a second posterior loosening of the electrode/patient interface.
to the medial malleolus proximal to the flexor retinaculum E-1. A tape measure is used to form a line connecting the an
forms a segment over which the NCV can be calculated. The terior superior iliac spine with the lateral border of the patella
distal stimulus site may be either 8 em or 10 cm proximal to the (Fig. 5-32). Approximately 16-18 cm distal to the anterior su
E-l electrode location for the medial plantar nerve measured perior iliac spine on the above noted line is the designated site
over the course of the nerve 1 cm posterior to the medial malle for E·l,33
olus with the ankle in a neutral position, i.e., 90°.102 Two dis £-2. E-2 is positioned 3 cm distal to E-l on the same line
tances are provided to accommodate for various foot sizes. connecting the anterior superior iliac spine and the lateral aspect
Instrumentation Parameters. See peroneal nerve. of the patella.
Reference Values. Reference data are provided for both Ground. The ground electrode should be positioned adja
stimulation distances with respect to cathodal placement (Table cent to E-l between the cathode and E-l. Again, the underlying
5-13). Acceptable temperature ranges are 29-34°C with a mean skin must be gently abraded to improve electrical contact. This
of 32.1 ± 1.4°C inferior to the medial malleolus. '02 is the same general location for all lower limb sensory tech
niques and is assumed to apply for each method.
LOWER LIMB SENSORY NERVE Stimulation. The cathode is located approximately 1 cm
CONDUCTION STUDIES medial to the anterior superior iliac spine. Although some au
thors use a needle cathode, one may wish to consider surface
There are a number of lower limb sensory nerve conduction stimulation. When a needle cathode is employed, a monopoiar
techniques important for the electrodiagnostic medicine practi needle is inserted 1 cm medial to the anterior superior iliac
tioner. The majority of lower limb SNAPs are slightly more spine. 33 A stimulating pulse delivered at a rate of 1 Hz with a
technically demanding than upper limb sensory methods. The moderately intense current is slowly inserted perpendicular to
primary reason for this increased demand in technical profi the skin surface until a paresthesia is described by the patient in
ciency is the small size of the responses. This small size is due the distribution of the nerve. Careful manipulation of the needle
in part to the size of the nerves investigated and the fact that and current is then performed until the response is optimized. A
unlike upper limb sensory nerves, in the lower limb the sensory surface anode may be located several centimeters proximal to
nerves are surrounded by more subcutaneous tissue. Also, we the cathode. The use of a surface cathode is also acceptable and
cannot encircle these nerves with a ring electrode and maximize is positioned at the same site noted for needle placement.
the contact between the recording electrode and neural tissue. Rotating the anode about the cathode may be of great assistance
The sensory nerve techniques discussed in this section are used in minimizing shock artifact. The locations of the stimulating
to evaluate the following nerves: lateral femoral cutaneous, pos and recording electrodes obviously result in an antidromic tech
terior femoral cutaneous, saphenous, superficial peroneal, and nique. Orthodromic techniques are also described, and are es
sural nerves. Although there are methods described to assess the sentially reversing the locations of the stimulator and recording
superficial fibers of the medial and lateral plantar nerves as they electrodes. 33,285
innervate the skin to the digits, these responses are very small Instrumentation Parameters. A sweep speed of 1 or 2
and in the authors' opinion unreliable. A mixed nerve technique ms/div with an amplifier sensitivity of lOll VIdiv should be suf
is presented in detail to evaluate nerve action potentials in the ficient to optimize detection of the response. Filter settings
214 - PART II BASIC AND ADVANCED TECHNIQUES
nerve trunk. Once below the popliteal fossa, it may extend for a
variable distance sharing innervation of the calf with the sural
nerve. This nerve is occasionally injured through injection in
juries or prolonged bicycle riding. 3J3
£-1. The E-l electrode is located in the midline of the poste
'-,:
rior thigh 6 cm proximal to the mid-popliteal fossa (Fig. 5-33).82
anterior superior £-2. The original technique used a bar electrode with a separa
iliac spine
tion of 3.0 cm. A separate disc electrode may also suffice as E-2.
Stimulation. A tape measure connecting E-l with the ischial
tuberosity forms a reference line with which to locate the cath
... ~
ode (Fig. 5-33). Twelve centimeters proximal to E-l on the
above-noted line is the desired stimulation site. The cathode is
positioned proximally and usually requires rotation to arrive at
an acceptable stimulus artifact.
Instrumentation Parameters. See lateral femoral cuta
neous nerve.
Reference Values. Negative peak latencies were noted to be
2.8 ± 0.2 ms (2.4-3.2 ms) with amplitudes of 6.5 ± 1.5 IlV
(4.4-11. 0 IlV).82
Saphenous Nerve
Of all the femoral nerve branches, the saphenous nerve is the
longest and largest. l44 It is a pure sensory nerve and is com
prised of lumbar segments L31L4. The cutaneous distribution of
this nerve is distributed to two main regions. The most proximal
is the infrapatellar area while the second covers the anterome
dial and posteromedial aspects of the leg. There is also a vari
able distribution along the medial aspect of the foot
occasionally extending to the base of the first digit. Approx
imately 4-5 cm distal to the inguinal ligament is where the
saphenous nerve becomes a distinct nerve as it separates from
the main trunk of the femoral nerve. The nerve then enters the
adductor canal deep to the sartorius muscle in the anteromedial
thigh. Just superior to the medial epicondyle of the femur and
posterior to the sartorius muscle, the saphenous nerve becomes
Figure 5-32. Lateral femoral cutaneous nerve. One can stimu subcutaneous traveling between the tendons of the sartorius and
late the lateral femoral cutaneous nerve either superior or inferior to
gracilis muscles. In the leg, the saphenous nerve is located pos
the inguinal ligament with a surface or needle cathode. The E-I (Ra)
terior to the medial edge of the tibia as it courses toward the
and E-2 (Rr ) recording electrodes are located 16 cm distal to the ante
foot. About 7 cm proximal to the medial malleolus the nerve
rior superior iliac spine on a line connecting this landmark with the
proceeds anterior and distal to it into the foot. The saphenous
lateral margin of the patella. (From Ma DM, liveson JA: Nerve
nerve terminates along the medial border of the forefoot at
Conduction Handbook. Philadelphia, F.A. Davis, 1983, with permission.)
times reaching the first metatarsophalangeal joint. This nerve
may be injured in the infrapatellar region either secondary to
approaching 10 Hz and 2 kHz are recommended to resolve the physical trauma or following surgical procedures to the knee.313
SNAP. Recording Electrodes. There are two popular techniques
Reference Values. Negative peak latencies are 2.6 ± 0.2 ms used in assessing antidromic saphenous nerve conduction, i.e.,
with a range of 2.3-3.1 ms. 33 Mean conduction velocities are re proximal and distal. Either may be used and serve as an alterna
ported at 47.9 ± 3.7 mls (43-55 mls) with negative peak ampli tive procedure when one fails to produce the expected response
tudes of 10-25 1lV. in a particular patient. The proximal method may yield slightly
larger responses, but the stimulation site is harder to locate, es
Posterior Femoral Cutaneous Nerve pecially in persons with significant subcutaneous tissue about
The posterior femoral cutaneous nerve is formed by the ante the knee. Distally, the anatomic landmarks are somewhat easier
rior and posterior divisions of sacral segments S l-S3 with occa to locate, but the nerve's diameter is reduced, resulting in rather
sional contributions from L4, L5, and S4.144 Once the nerve small potentials. Patient relaxation is paramount in attempting
exits the pelvis, it passes anterior to the piriformis muscle and to record saphenous SNAPs.
posteromedial to the sciatic nerve. Inferior to the piriformis
muscle, multiple small branches are given off to innervate the Proximal Recording
perineum and inferior gluteal area. The main portion of the pos £-1. The knee is slightly flexed at 10-20°. The E-l recording
terior femoral cutaneous nerve then comes to lie in the inter electrode position is located by first palpating the tendons of the
muscular groove between the medial and lateral hamstring sartorius and gracilis muscles 1 cm proximal to the inferior
muscles. Traversing the posterior thigh in this location, the border of the patella (Fig. 5_34).216 On a line 15 cm distal to the
nerve provides cutaneous sensation to the posterior aspect of the previously noted site to the medial border of the tibia, an E-l
thigh through numerous small branches arising from the main electrode is secured to the patient. Sufficient tape is required to
Chapter S NERVE CONDUCTION STUDIES - 21 S
- LoUIIJIII Iamoral
c:utanIOu$
.......lsur.1
cutaneous
Distal Recording
E-1. For recording the saphenous nerve SNAP distally, the
E-I electrode is positioned in the anatomic depression just pos
terior to the tibialis anterior tendon 3 em proximal to the medial
malleolus' greatest prominence at the ankle region. 350
E-2. E-2 is placed posterior to the tibialis anterior tendon and
anterior to the medial malleolus' largest prominence.
Proximal Stimulation. The cathode is located at the pre
viously designated site between the sartorius and gracilis
tendons I em proximal to the inferior border of the patella
with the anode proximal (Fig. 5-34). Firm pressure combined
Figure 5-33. Posterior femoral cutaneous nerve. Recording with a pulse duration of 0.1 or 0.2 ms may be required to op
and stimulating electrode location for evaluation of the posterior timally excite the saphenous nerve in this location depending
femoral cutaneous nerve. (From Dumitru 0, Nelson MR: Posterior upon the amount of subcutaneous tissue. Stimulus artifact
femoral cutaneous nerve conduction. Arch Phys Med Rehabil may pose a particular problem with this SNAP because of the
1990;71:979-982, with permission.) small size and difficulty in obtaining the response. As a
result, the practitioner is strongly encouraged to rotate the
anode about the cathode prior to concluding that the re
maintain the electrode in the depression posterior to the tibia sponse is unobtainable.
and the practitioner may wish to apply slight pressure to this Distal Stimulatiou. Cathodal placement is 14 em proximal
electrode with a plastic pen during recording. to E-l between the medial border of the tibia and the gastrocne
E-2. A surface E-2 electrode is placed 3 em distal to E-l mius muscle in the anatomic depression between these two
along the medial border of the tibia in the anatomic depression structures. Similar comments regarding stimulus artifact noted
between the tibia and the gastrocnemius muscle. above for proximal stimulation apply.
216 - PART II BASIC AND ADVANCED TECHNIQUES
Instrumentation Parameters. See lateral femoral cuta Recording Electrodes. E-1. A bar electrode with an inter
neous nerve. electrode separation of 3 cm is located posterior to the lateral
Reference Values. With proximal stimulation, the latency malleolus with E-l proximal. E-l should be located at approxi
measured to the SNAP's onset is noted to be 2.5 ± 0.2 ms mately the level of the major prominence of the lateral malleolus.
(2.2-2.8 ms) with peak-to-peak amplitudes of 10.2 ± 2.1 ~V E-2. An E-2 electrode imbedded in the plastic bar is posi
(7.0-15.0 ~V).216 Conduction velocity for this technique is 58.8 tioned as close to the lateral malleolus as possible without com
± 2.3 mls (53.7-63.7 mls). For distal stimulation, peak latency promising E-J 's location.
is 3.6 ± 0.4 ms with a mean amplitude of 9.0 ± 3.4 ~V and con Stimulation. On a line 14 cm proximal to E-l the sural
duction velocity approximating 41.7 ± 3.4 mlS.350 nerve is stimulated with the cathode distal just lateral to the
leg's midline. Slight medialllateral movement may be necessary
Superficial Peroneal Sensory Nerve to position the cathode directly over the sural nerve. This is
The superficial peroneal sensory nerve is the cutaneous con achieved when the amplitude of the response is maximal. The
tinuation of the superficial peroneal nerve that arises from the patient should describe a paresthesia associated with the stimu
common peroneal nerve and is composed preferentially of nerve lus along the lateral aspect of the foot.
fibers originating from the L5 segment. 144 This nerve becomes Instrumentation Parameters. See lateral femoral cuta
subcutaneous in the anatomic depression between the peroneus neous nerve.
longus and extensor digitorum tendons at the proximal portion Reference Values. At 14 cm with a skin temperature of
of the distal third of the leg. It travels anterior to the extensor about 32.2 ± 1.2°C, negative peak latency of 3.5 ± 0.2 ms with a
retinaculum at the ankle as two distinct sensory branches, i.e., conduction velocity of 39.6 ± 2.3 mls and amplitude between
the intermediate and medial dorsal cutaneous nerves of the 10-50 flV is described. 292
fOOt. 154 These nerves provide cutaneous sensation to the antero
lateral aspect of the distal leg area and the majority of the foot's Medial/Lateral Plantar Compound
dorsum except for that region between the first and second Nerve Action Potentials
digits that is innervated by the deep peroneal nerve. A number of techniques exist to evaluate the sensory nerve
Recording Electrodes. A number of orthodromic and an distribution of the medial and lateral plantar nerves, but the re
tidromic techniques have been developed to examine this sponses are rather small and inconsistently obtained. Near-nerve
nerve; however, only a reliable and simple antidromic tech needle recordings have also been described for orthodromic
nique is described. 157 evaluation of the mediaillateral plantar nerves, but most practi
E-1. This method records the response only from the inter tioners prefer surface stimulation and recording. As a result, a re
mediate dorsal cutaneous branch of the superficial peroneal sen liable surface method of evaluating the mixed nerve action
sory nerve as it crosses the ankle. An E-l electrode is positioned potential of the medial and lateral plantar nerves is described.
1-2 cm medial to the lateral malleolus. It is important to note Beneath the flexor retinaculum, the tibial nerve divides into
that this technique uses a bar electrode with an interelectrode the calcaneal, medial, and lateral plantar nerves. 65 The medial
separation of 3 cm. Slight repositioning may be required to opti and lateral plantar nerves proceed into the foot to innervate the
mally locate the nerve branch under investigation secondary intrinsic foot muscles. Specifically, the medial plantar nerve
slight anatomic variations. innervates the following muscles: abductor hallucis, flexor digi
E-2. The E-2 electrode imbedded in the plastic bar is located torum brevis, flexor hallucis brevis, and first dorsal in
distally. terosseous. l44 The remaining foot muscle are innervated by the
Stimulation. The cathode is located 12 cm proximal to E-l lateral plantar nerve: abductor digiti minimi, flexor digiti
firmly pressed into the soft tissue just anterior to the anterior minimi, adductor hallucis, and flexor digitorum brevis. The
margin of the fibula. A pulse duration of 0.05 ms is recom medial and lateral plantar aspects of the foot are innervated by
mended but some individuals may require a slightly greater the medial and lateral plantar nerves, respectively. Also, the
pulse duration. medial three and one-half digits are supplied by the medial
Instrumentation Parameters. See lateral femoral cuta plantar nerve while the remainder receive cutaneous innervation
neous nerve. from the lateral plantar nerve.
Reference Values. The negative peak latency is noted to be Recording Electrodes. E-1. An E-l electrode imbedded in
2.9 ± 0.3 ms with a negative peak amplitude of 20.5 ± 6.1 ~V a plastic bar with an inter-electrode separation of 3 cm is posi
and a conduction velocity of 65.7 ± 3.7 mlS.157 tioned with E-l just proximal to the superior edge of the flexor
retinaculum over the tibial nerve. 282 This site is located by con
Sural Nerve necting an imaginary line between the posterior tip of the calca
Two branches, one from the tibial (medial sural nerve) and neus and the medial malleolus' prominence (Fig. 5-35). E-I is
the other from the peroneal (lateral sural nerve) nerve fuse just located just proximal to this line. The bar electrode is firmly
inferior to the popliteal fossa region to form the sural nerve pressed into the space posterior to the medial malleolus and se
proper. The sural nerve has representation from primarily the SI cured with as much tape as necessary to maintain close contact
nerve roOt. l44 Proximally, the sural nerve traverses the groove with the skin.
between the two head of the gastrocnemius muscle. At about the E-2. The E-2 electrode is positioned proximal to E-I on the
proximal lower third of the leg, it becomes subcutaneous and tibial nerve.
continues distally posterior to the lateral malleolus. The sural Stimulation. The site for medial plantar n..:rve excitation is
nerve then terminates along the lateral border of the foot. The located by first measuring 10 cm from E-I to th.: interspace be
cutaneous regions innervated by the sural nerve are the distal tween the first and second metatarsals on the plantar aspect of
dorsal lateral aspect of the leg and lateral portion of the foot. the foot. One then continues an additional 4 cm toward the
Although multiple techniques have been described, only a reli digits on this inter-metatarsal line to stimulate the medial plan
able antidromic method is described.292 tar nerve (Fig. 5-35). The cathode is situated such that it faces
Chapter 5 NERVE CONDUCTION STUDIES - 217
CONCLUSION
After completing this chapter, one can appreciate the intricate
interconnections between neural anatomy and impulse conduc
tion. The anatomic arrangement of the nerve on a microscopic
level serves to provide a flexible and strong "cable" system tc
convey a self-sustaining action potential. This action potentia
can be used to determine the peripheral nervous system's physi·
ologic status with respect to health or disease. Multiple tech·
niques are available to assess individual nerve integrity in bott
the upper and lower limbs. It is essential for the practitioner tc
master most of these techniques without referring to a technical
manual. This is possible only with a great deal of practice nndel
the supervision of a recognized expert. All of the previous prin
ciples of volume conduction and instrumentation converge on
the proper performance of technically demanding nerve con
duction techniques. The information gained from the nerve con
duction portion of the electrodiagnostic medicine consultation
is combined with the history and physical examination to assist
in the formation of an appropriate diagnosis.
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Chapter 6
CHAPTER OUTLINE
Once the practitioner has mastered the basic nerve conduc proximal nerves and assess neural conduction time across the
tion techniques, it is important to pursue more specialized plexus. Conduction times as opposed to conduction velocities are
methods of evaluating the peripheral nervous system. Ad preferred as it is difficult to accurately measure the neural seg
ditionally, nerves requiring needle excitation and less com ment's length. Nerve root stimulation is a relatively advanced nerve
monly studied nerves are of importance. From time-to-time conduction technique and should only be attempted once the fun
patients may present with lesions affecting specific sensory damentals of more routine procedures are mastered. Nerve roots
branches that yield small amplitude responses or require aver can be stimulated electrically with needle electrodes and magneti
aging techniques to better define the desired waveform. With cally with a coil over the skin. Because root stimulation with needle
the majority of nerve conduction studies described in this chap electrodes can be done with standard apparatus, this technique is
ter, the difficulty lies not in the inherent technique or nerve, but described in the following sections. It is presumed that with
more so in unfamiliarity. Most, if not all, of the techniques de monopolar needle stimulation the root is depolarized just proximal
scribed in this chapter can be mastered with simple practice to the intervertabral foramen.142
and repetition.
Nerve Roots CS-C6
Because the nerve roots are located under a relatively sig
MOTOR NERVE CONDUCTION STUDIES nificant amount of muscle tissue, attempts to localize just one
nerve root in a "blind" manner is rather difficult. Addi
A number of motor nerve conduction studies can be per tionally, considerable expertise in addition to adjunctive fluo
formed. By stimulating specific nerve roots or Erb's point and roscopy is required to accurately localize a particular root
recording from particular muscles, it is possible to selectively level. A more simple yet effective approach is to place the
evaluate distinct portions of the brachial or lumbosacral stimulating cathode (needle electrodes are required) just lat
plexus. Conduction times across the hial plexus also can be eral to the spinous process (see below) so that it overlies the
assessed. posterior arch of the cervical vertebrae, thus preventing the
needle from piercing the nerve root or other vital neurovascu
NERVE ROOT STIMULATION lar structures.
Recording Electrodes. When stimulating the C5-C6 nerve
The purpose of attempting to stimulate the nerve roots and roots, recordings are typically obtained from the biceps brachii
record CMAPs is primarily to evaluate conduction in various muscle. This muscle allows the practitioner to assess neural
225
226 - PART II BASIC AND ADVANCED TECHNIQUES
bony arch is contacted (Fig. 6-2). The needle cathode is then I --------.,. ~r----
withdrawn several millimeters. Again, a contralateral needle
anode is possible or an ipsilateral surface anode located several
~ ___i ~25cmi
centimeters distal to the needle insertion site. The onset latencies
for left and right abductor digiti minimi CMAPs are recorded. Stimulation of Median
A second stimulus is then applied at the axilla on a line 2S cm and Ulnar Nerves
in length from the mid-sternal notch with the arm abducted 90°
and externally rotated (Fig. 6-3). This procedure is repeated for
the contralateral limb. The onset latencies to the left and right Figure 6-3. Axilla stimulation. location for arm stimulation of
abductor digiti minimi muscles are recorded to the CMAP's ini the median and ulnar nerves used in conjunction with C8rr I nerve
tial departure from baseline. Onset latencies from axillary stim root stimulation to assess conduction time across the brachial plexus.
ulation are subtracted from the nerve root excitation latencies to The arm is externally rotated and abducted. Stimulation of the median
arrive at a transbrachial plexus conduction time. and ulnar nerves is performed 25 cm from the sternal notch over the
Instrumentation Parameters. See CS-C6 nerve root stimu neurovascular bundle in the arm. (From Maclean IC: Spinal nerve stim
lation. ulation. In AAEM Course B: Nerve Conduction Studies-A review
Reference Values. The range of conduction times across the course. Rochester, MN, American Association of Electrodiagnostic
brachial plexus is 3.7-S.S ms with a mean of 4.7 ± O.S ms (Table Medicine, 1988, with permission.)
228 - . PART II BASIC AND ADVANCED TECHNIQUES
with respect to potential pathology. Specifically, techniques fingers. A standard concentric needle electrode is then carefully
have been developed to examine a number of these proximal inserted between the two fingers until the rib is encountered and
nerves, including long thoracic, suprascapular, axillary, muscu then withdrawn just a few millimeters. The response is mea
locutaneous, and proximal radial nerves. Each of these nerves sured to the initial deflection from the baseline.
innervates a muscle that can easily be used to record from; how £-2. In a surface recording, an E-2 is positioned on the same
ever, the individual nerves are not readily accessible. As a result, rib as E-1 several centimeters anteriorly. Of course, if a standard
it becomes necessary to deliver a rather strong depolarizing concentric needle is used, the cannula serves as E-2.
pulse to the brachial plexus as a whole in an attempt to activate Stimulation. Stimulation is carried out at Erb's point with
in a supramaximal manner all of the above-noted nerves. This an intensity and pulse duration capable of delivering a supra
can be accomplished if the excitation pulse is delivered at Erb's maximal excitation. A pulse duration between O.S and 1.0 ms is
point. usually sufficient to achieve the desired result. Initially, the pa
Recording Electrodes. Because of the nature of the stimu tient can be requested to turn the head opposite to the side of
lus producing depolarization of the brachial plexus as a whole, stimulation, making accurate identification of Erb's point rela
one can record from multiple muscles simultaneously provided tively easy. Once Erb's point is localized, the patient's head can
one's instrument possesses more than one channel. This is ad be turned slightly toward the stimulus site just past midline.
vantageous because it limits the number of rather intense shocks This is necessary to relax the skin and subcutaneous tissues al
delivered to the patient. Also, the original studies described lowing the practitioner to position the cathode (distal) and
below used intramuscular recordings with standard concentric anode as deeply into the supraclavicular fossa as possible with
needle electrodes, thus limiting the utility of amplitudes. out producing undue patient discomfort. It is anticipated that the
entire plexus will be activated, but an attempt should be made to
Long Thoracic Nerve confirm contraction of the serratus anterior by palpating the
The long thoracic nerve arises directly from cervical nerve muscle over the anterolater aspect of the rib cage.
roots CS-C7 and innervates the serratus anterior muscle. 95 .96 Instrumentation Parameters. See nerve root stimulation.
This muscle is of clinical value because its nerve originates Reference Values. Onset latencies to the initial deflection of
proximal to the formation of the brachial plexus and may help the response are in the range of 2.6-4.0 ms (Table 6_2).29,111
to assess the extent of a possible brachial plexus injury. Should
this nerve be spared, it suggests that the injury site is distal to Suprascapular Nerve
the CS-C7 root level. The suprascapular nerve originates just distal to the formation
Recording Electrodes. Surface recording electrodes are of the brachial plexus' upper trunk and is composed of nerve
typically used for this study; however, there is a report of fibers from CS-C6. 96 This nerve then proceeds posteriorly
monopolar needle recordings from this muscle.29.111 The use of through the suprascapular notch to innervate the supraspinatus
surface recording electrodes is understandable given the prox muscle. The nerve continues to course around the lateral aspect
imity of this muscle to the chest wall and the potential for inad of the scapula to innervate the infraspinatus muscle. We describe
vertently piercing the intercostal space and possibly producing a latencies to both the supraspinatus and infraspinatus muscles.
pneumothorax. Recording Electrodes. The majority of recordings from
£-1. An E-1 surface recording electrode is positioned over proximal muscles following Erb's point stimulation are per
the fifth or sixth rib at the midaxillary line. In persons with sig formed with standard concentric needle electrodes, although it
nificant subcutaneous tissue, an intramuscular E-1 may be is possible to also use monopolar needles.
preferable for recording the response's latency. If a standard Supraspinatus Muscle. E-1. A standard concentric needle
concentric needle is chosen, it is imperative to use proper tech electrode is located in the supraspinatus muscle midway be
nique to avoid the possibility of inducing a pneumothorax. The tween the medial border of the scapula and the acromion.72
interspaces flanking the desired rib must be identified by palpat Using obstetric calipers, two separate distances were measured
ing the interspaces and locating the rib between the palpating from the center of the cathode/anode at Erb's point to the
recording locations for the supraspinatus muscle. The two mean
distances were 8.S cm and IO.S cm for respective E-1 locations.
Table 6-2. Erb's Point Stimulation
This allows the practitioner to choose one of the distances most
Nerve Recording Latency (ms) appropriate to the size of the patient. Surface electrodes are of
Long thoracic 29.1II Serratus anterior 2.6-4.0 questionable value for this muscle because of the overlying
Suprascapular72
trapezius muscle that may diminish the CMAP's magnitude.
Supraspinatus (8-9 cm) 2.6 ± 0.07
£-2. When using standard concentric needle electrodes, the
Supraspinatus (10-11 cm) 2.7 ± 0.07
cannula serves as the E-2 recording electrode. If a monopolar
Suprascapular72 Supraspinatus (7.4-12 cm) 2.7 ± 0.5 needle is used as E-2, it should be located several centimeters
Suprascapular72 Infraspinatus (13-15 cm) 3.4 ± 0.09 lateral to E-l. 143
Infraspinatus (16-18 cm) 3.4 ± 0.13 Stimulation. A surface cathode and anode are located at
Suprascapularl28 Infraspinatus (10.6-15 cm) 3.3 ± 0.5 Erb's point. The pulse duration should be between 0.5 and 1.0
ms with an intensity capable of producing a supramaximal re
Musculocutaneous 128.223 Biceps brachii (19-21 cm) 4.6 ± 0.14 sponse. Firm pressure applied at Erb's point is often necessary
Biceps brachii (23-25 cm) 4.7 ± 0.15 to evoke an optimal response. See long thoracic nerve for de
Biceps brachii (27-29 cm) 5.0 ± 0.13
tails of head positioning.
Axill ary72.128 Deltoid (15-16 cm) 4.3 ± 0.11 Instrumentation Parameters. See nerve root stimulation.
Deltoid (18-19 cm) 4.4 ± 0.08 Reference Values. The onset latencies to the initial deflec
Recording performed with standard concentric needle electrodes and ampli tion of the response is recorded for either distance chosen (Table
tudes not recorded. 6-2).
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 229
Infraspinatus Muscle. E-1. A standard concentric needle recorded with a concentric needle electrode can range between
electrode is inserted into the mid-portion of the infraspinatus 6 and 32 mY.
muscle 14 cm and 17 cm from the stimulation site at Erb's
point. This distance is measured with obstetric calipers. Axillary Nerve
E-2. See supraspinatus muscle. The axillary nerve, also called the circumflex nerve, is
Stimulation. See supraspinatus muscle. formed by nerve roots C5-C6.% This nerve arises from the pos
Instrumentation Parameters. See nerve root stimulation. terior cord of the brachial plexus. There are two muscles inner
Reference Values. As for the supraspinatus, the initial onset vated by the axillary nerve: teres minor and deltoid. The
latency is of interest (Table 6-2). relevant anatomy of the axillary nerve is that it courses through
the quadrilateral (quadrangular) space, i.e., teres minor supe
Musculocutaneous Nerve riorly, teres major inferiorly, surgical neck of the humerus later
The musculocutaneous nerve is the continuation of the ally, and long head of the triceps muscle medially. This nerve
brachial plexus' lateral cord and consists of fibers from nerve then travels posterolaterally around the humerus to divide into
roots C5-C7. 95 This nerve innervates the coracobrachialis, anterior and posterior neural branches to innervate the deltoid
biceps brachii, and brachialis muscles. It is possible to injure muscle. Dislocations or fractures of the humerus may injure the
this nerve as a result of shoulder dislocations. axillary nerve.
Recording Electrodes. Because of a relatively well defined Recording Electrodes. The accessibility of the deltoid
motor point along a band in the middle of the biceps brachii muscle permits surface-recording electrodes to be used. 128
muscle, surface electrodes can be used to obtain a CMAP.128 It Standard concentric needle electrodes have also been used to
is also possible, however, to use standard concentric needle record onset latencies.72
electrodes (Table 6-2). E-1. If a surface E-I electrode is chosen, it should be secured
E-1. When recording with surface electrodes E-l is located to the most prominent portion of the deltoid muscle in the upper
at the mid-point of the biceps brachii muscle. A standard con lateral aspect of the arm. The mid-portion of the muscle con
centric needle electrodes is placed in the muscle at 20 cm, 24 tains the motor point and a recording from this region should
cm, or 28 cm depending upon the patient's stature. As for the result in a well-defined negative onset. The use of a standard
suprascapular nerve, this distance is measured with obstetric concentric needle electrode requires the needle to be placed
calipers from the Erb's point stimulation site. deep in the substance of the muscle. As for needle recordings
E-2. In the surface recording technique, E-2 is located on the from other proximal muscles, there are several distances mea
biceps brachii tendon in the antecubital fossa. As previously sured with obstetric calipers from the point of stimulation to ac
noted, the cannula of the standard concentric needle electrode count for different arm lengths. The distances for E-l placement
serves as E-2. are 15.5 cm and 18.5 cmJ2
Stimulation. There are two stimulation techniques for elicit E-2. For a surface recording, E-2 is located at the tendinous
ing a CMAP from the biceps brachii muscle. It is possible to insertion of the deltoid muscle in the mid-arm area. As previ
either stimulate Erb's point l28 or directly excite the musculocu ously noted, the cannula is the E-2 electrode for concentric
taneous nerve in the anterior aspect of the axilla. 223 The latter needle recordings.
stimulation site more selectively activates the musculocuta Stimulation. See long thoracic and suprascapular nerves.
neous nerve as opposed to activating the entire brachial plexus Instrumentation Parameters. See suprascapular nerve.
and may be of use during repetitive stimulation studies obviat Reference Values. Onset latencies are similar for both stan
ing the need to excite the entire brachial plexus. Stimulation at dard concentric needle and surface recordings (Table 6-2). It is
Erb's point is performed as previously noted for the long tho important to recall that should a needle recording be used, the
racic and suprascapular nerves. needle electrode is placed deep into the substance of the muscle
When attempting to directly excite the musculocutaneous to avoid erroneously long latencies. 102 Only surface recordings
nerve in the arm, one can use either surface or needle stimula are optimal for comparing side-to-side amplitudes.
tion. For surface stimulation, the cathode is positioned close to
the insertion of the pectoralis major muscle on the humerus Nerve Root Stimulation: Lumbosacral
distal and somewhat posterior to its inferior margin, whereas the Plexus Conduction Latencies
anode is located proximally. A needle cathode is located be It is possible to evaluate conduction across the lumbosacral
tween the coracobrachialis tendon laterally and the axillary plexus by stimulating the nerve roots constituting the plexus and
artery medially just proximal to the latissimus dorsi tendon. subtracting the time of conduction from either the femoral or sci
Similar parameters for needle stimulation previously noted are atic nerves. The lumbar plexus is assessed by simultaneously ex
again used. The needle anode is located transversely at a dis citing roots L2-L4 and recording a response from the vastus
tance of 3 cm. medialis muscle. 96 The femoral nerve is depolarized in the in
Instrumentation Parameters. See suprascapular nerve. guinal region. The femoral nerve latency is then subtracted from
Reference Values. When using a surface recording elec the root latency and a conduction time across the lumbar plexus
trode the latency is measured to the initial deflection of the re results. For sacral plexus analysis, a CMAP from the AH is ob
sponse (Table 6-2). Unlike needle electrodes, the amplitude of tained following L5-S 1 nerve root activation. The sciatic nerve is
the surface-recorded CMAP best reflects the summated re then stimulated at the gluteal fold. This latency is subtracted from
sponse of the muscle and may be used for diagnostic purposes. the L5-S 1 latency for a trans-sacral plexus conduction time.
Amplitudes obtained with needle recording should be used with Recording Electrodes. Surface recording electrodes for the
caution regarding any attempt to quantify axonal loss. femoral and sciatic nerves are used to calculate lumbosacral
If the musculocutaneous nerve is directly excited in the conduction times.
axilla, one can anticipate onset latencies in the range of 1.3-3.6 Lumbar Plexus (L2-L4). E-1-E-2. See femoral nerve
ms for recording distances of 7-13 cm. 223 Peak-to-peak amplitudes (Chapter 5).
230 - PART II BASIC AND ADVANCED TECHNIQUES
Conduction Across Sacral Plexus (L5-S1). £-1-£-2. See sciatic nerve (Chap
Lumbar Plexus ter 5).
Stimulation (L2-L4). A monopolar needle electrode 75 mm
in length is used for the cathode. Approximately 2-2.5 cm lat
eral to the spinous process of the L4 vertebral body, a needle
cathode is inserted perpendicularly to the skin in a sagittal plane
(Fig. 6_4).142 The needle is positioned on the periosteum of the
vertebral arch overlying the L4 nerve root. The anode, a similar
needle electrode to the cathode, is located in the same position
on the contralateral aspect of the body. Stimulation as described
above allows one to activate the lumbar nerve roots bilaterally.
It is important to rest the tip of the cathode and anode on the
posterior bony aspect of the vertebral arch and not the inferior
or superior interspaces. Sufficient current is delivered by adjust
ing both the intensity and pulse duration to achieve a supramax
imal response. The patient should be sufficiently warned as this
can be uncomfortable.
Stimulation (L5-S1). The same needle cathode and anode
used for lumbar stimulation are also used for excitation of
L5-S 1 nerve roots (Fig. 6_5).144 In this instance, however, the
cathode/anode are inserted perpendicular to the skin surface just
medial and a bit caudal to the posterior superior iliac spine.
Similar comments noted above for L2-L4 nerve root excitation
also apply to activating L5-S1 nerve roots.
Instrumentation Parameters. See femoral and sciatic
nerve conduction study instrumentation recommendations
(Chapter 5).
Reference Values. Calculated means, ranges, and left/right
differences are provided for lumbosacral nerve root stimulation
Figure 6-4. L2/L3/L4 nerve root stimulation. Needle electrode (Table 6-3).
placement for activation of the l2/L3/l4 nerve roots. Additionally.
stimulation of the femoral nerve is depicted for the determination of CRANIAL NERVE CONDUCTION STUDIES
transplexus conduction times. (From Maclean IC: Spinal nerve stimu
lation. In AAEM Course B: Nerve Conduction Studies-A review Three of the cranial nerves can be readily studied with rou
course. Rochester, MN, American Association of Electrodiagnostic tine nerve conduction studies previously described for upper
Medicine, 1988, with permission.) and lower limb peripheral nerves. The cranial nerves discussed
in this text are: cranial nerve VII (facial nerve), cranial nerve V
(trigeminal nerve, afferent component only), and cranial nerve
Conduction Across XI (spinal accessory nerve). The techniques discussed are per
Sacral Plexus formed with surface stimulation and recordings and of proven
value in the authors' experience.
finally the parasympathetic supply to the lacrimal and salivary thereby avoiding coexcitation of the masseter muscle. 152 Of
glands. The anatomic course of the facial nerve can be separated course, the latency is significantly shortened in this case, but the
into an intracranial and extracranial portion. Intracranially. the response is acceptable for side-to-side amplitude comparisons.
seventh nerve arises from the pons to enter the facial canal via E-l. The E-l surface-recording electrode can essentially be
the internal auditory meatus. The facial canal consists of the placed on any facial muscle desired. Three commonly examined
labyrinthine. tympanic. and mastoid segments of which the muscles are the orbicularis oculi, orbicularis oris, and nasalis
labyrinthine is the smallest. 55 •56 The termination of the mastoid (Fig. 6-6). Should the orbicularis oculi be chosen for recordings,
segment, stylomastoid foramen, is where the facial nerve exits the E-I electrode is usually positioned inferior to the eye's
the skull to begin its extracranial course. After exiting the skull, lower canthus aligned with the pupil or at some point laterally
the nerve enters the substance of the parotid gland and divides to the outer margin of the eye. Some repositioning of the elec
into a number of divisions to innervate various muscles of facial trode may be required to achieve an initial negative deflection.
expression. These muscles are relatively easy to evaluate with For orbicularis oris recordings, E-l is located at the angle of the
nerve conduction techniques because of their superficial loca mouth just lateral to where the upper and lower lips join. The
tion. Also, the facial nerve can be readily excited anterior to the nasalis muscle area is perhaps the easiest region to record from
earlobe. when exciting the facial nerve (Fig. 6-6). It is located by having
Recording Electrodes. As previously noted, only surface the patient "crinkle" the nose as if a foul scent has been encoun
recordings are described as this method provides the best as tered. The prominent bulge just superior to the lateral nasal ala
sessment of the total number of muscle fibers excited. is the nasalis muscle area. The paretic side should be compared
Essentially any muscle can be used to record a CMAP follow with the normal side in order to properly position the electrode.
ing facial nerve activation. This gives the opportunity to selec Recording from the nasalis muscles usually result in the best
tively measure the different branches of the facial nerve (e.g., CMAPs.l86
zygomatic, mandibular etc.). Facial muscles do not necessarily If amplitude is not of interest when performing facial nerve
have well-defined motor points and subsequently may yield recordings, it is acceptable to use standard concentric needles
CMAPs with an initial positive deflection. One can attempt to placed into the muscle under investigation. Relatively sharp
reposition the electrodes, but this may not always result in a onsets of either a positive or negative direction should be ob
waveform with an initial negative onset. When this occurs, one tained. It is important to remember, however, that the amplitude
is advised to accept the response and measure the onset latency
to the beginning of the initial positive deflection. When calcu
lating the amplitude of any CMAP, it is better to measure the
potential from the initial negative deflection to the peak of the
negative spike. If it is impossible to obtain an initial negative
deflection, an initial positive to subsequent negative peak suf
fices. The major value in facial nerve studies with respect to
prognosis is comparing side-to-side amplitudes. 55 ,56 Hopefully,
both sides of the face have similar-appearing potentials for com
parison purposes. There may be occasions when one side of the
face has a pronounced positive deflection, whereas the con
tralateral side begins with the expected negative deflection. This
poses a significant problem for comparative evaluations. If
repositioning the E-I electrode with the positive deflection does
not resolve the problem, one cannot use two morphologically nasalis
different CMAPs for comparative purposes. All factors being
equal (recording electrode position, stimulus location, current
pulse width and intensity, and manual pressure on all elec
trodes), a marked side-to-side amplitude discrepancy of greater
than 50% is suspicious. This is a conservative estimate as
normal side-to-side variations may reach approximately
3_20%.55.56.103.104 One may wish to proceed to a different muscle
in the hope of finding relatively symmetric CMAPs for left and
right sides of the face.
A second problem in facial nerve studies is a volume-con
ducted response from the masseter. When stimulating the facial
nerve anterior to the earlobe it is relatively easy to directly acti
vate the masseter muscle. In patients with profound facial nerve
loss, a volume-conducted masseter CMAP can coincide with /
the expected facial nerve response's position and be mistaken
for a facial CMAP. The practitioner must be aware of this poten Figure 6-6. Facial nerve activation. The facial nerve is stimulated
tial problem to avoid an erroneous conclusion that there is facial either anterior or posterior to the ear (5) with subsequent recording
nerve function when indeed this nerve may have undergone from any facial muscle. In the above diagram a recording from the left
complete degeneration. Should this be encountered, it behooves nasalis (E-I:R.) is depicted with E-2 (Rr) on the superior aspect of the
the practitioner to palpate the masseter muscle for a contraction nose away from muscle tissue. We believe the posterior stimulation is
when stimulating the facial nerve. There is also a recommenda preferable. (From Ma OM, liveson JA: Nerve Conduction Handbook.
tion to excite the facial nerve as it passes beneath the zygoma, Philadelphia, F.A. Davis, 1983, with permission.)
212 - PART II BASIC AND ADVANCED TECHNIQUES
obtained with needle recordings is not valid to be used for as side-to-side amplitudes within the first 2 weeks following a
sessing axonal loss with respect to prognosis. lesion such as Bell's palsy, sparing of 10% or more ofthe re
E-2. A surface E-2 is usually located in an area devoid of sponse compared to the uninvolved side suggests a good prog
muscle if at all possible. The most likely location on the face is nosis for recovery.55.56 Normal threshold stimulation currents are
on the tip or bridge of the nose as it is mostly cartilage or bone between 3.0-8.0 rnA with a side-to-side difference less than 2.0
(Fig. 6-6). Although this location is not "electrically silent," it is mA.125
a convenient location to assist in differential amplification and
common mode rejection. Of course, should a standard concen Cranial Nerve V (Trigeminal Nerve)
tric needle be used, the cannula serves as E-2. That aspect of the trigeminal nerve capable of being exam
Ground. As with other nerve conduction techniques, the ined with peripheral nerve stimulation involves primarily the
ground electrode should be located close to E-I between it and sensory afferent fihers originating in the supraorbital nerve.
the cathode. This nerve can be located by palpating the supraorbital notch
Stimulation. Surface stimulation can be applied to one of along the medial aspect of the supraorbital ridge. Afferent im
two convenient locations. A cathode may be placed either ante pulses arising from the cutaneous distribution of this nerve,
rior or posterior to the earlobe (Fig. 6-6). Anteriorly, the cathode vertex of skull to supraorbital area, travel to their cell body lo
is pressed into the substance of the parotid gland several cen cated in the trigeminal ganglion.90 From this ganglionic region,
timeters superior to the angle of the mandible. Slight the action potentials travel into the pontine portion of the central
superior/inferior movement may be required to optimally locate nervous system and apparently diverge into two separate path
the facial nerve. Postauricular activation of the facial nerve is ways. An oligosynaptic path proceeds superiorly to synapse in
accomplished by positioning the cathode posterior to the neck the principle sensory nucleus (Fig. 6-7). A second-order path
of the mandible inferior to the mastoid process. Again, it is im way then travels caudally to synapse with the facial nerve nu
portant to avoid direct masseter activation. 42-44,74 Despite recom cleus causing depolarization of this structure with an ensuing
mendations in the literature, we strongly believe that all facial contraction of the orbicularis oculi muscle ipsilateral to the side
nerve stimulations should occur in proximity to the stylomas of excitation. A second pathway from the point of divergence in
toid foramen, i.e., behind the ear. the rostral pons courses caudally in the lateral medullary plate
Because there are several parameters one can measure fol region a variable distance (Fig. 6-7). At some point in the lower
lowing facial nerve stimulation, the characteristics of the stimu medulla and several synapses later, two separate tracts head su
lator must be specified. If facial nerve latency or amplitude is of periorly, both ipsilateral and contralateral to the side of stimula
primary interest, then either a constant-current or constant-volt tion. These two pathways eventually synapse with their
age stimulator with sufficient current intensity capable of deliv respective facial nerve nuclei and induce a contraction of both
ering a supramaximal response is all that is required. On the orbicularis oculi muscles, which is the clinically observed blink.
other hand, should one wish to measure the amount of current The above described and presumed pathway describes the elec
necessary to evoke just a minimal facial muscle contraction, a trically induced "blink reflex."125 Apparently, a relatively strong
constant-current stimulator with a pulse width of 0.2-0.5 ms is depolarization of this nerve is required to generate a blink reflex
necessary. It is very easy to stimulate the facial nerve intracra as cutaneous stimulation to the distribution of the supraorbital
nially with a magnetic stimulator. In contradistinction with nerve does not produce the clinically observed blink response.
magnetic root stimulation, it is possible to obtain maximal The above-described pathway is believed to be slightly different
CMAPs, even with low stimulus strength. The magnetic coil is than that taken by impulses generated with tactile stimulation of
positioned over the parietal region. The facial nerve is depolar the cornea, i.e., the clinical blink reflex.
ized just at the proximal part of the facial canal. 186.199 Attempting The electrical blink reflex examines the afferent trigeminal
to define the minimal amount of current that just produces a tract through the supraorbital nerve and the efferent facial
minimal twitch of a facial muscle is known as the nerve ex nerve pathway to the orbicularis oculi muscle. It is possible to
citability test (NET). elicit a blink reflex with excitation of the infraorbital and
To perform a NET study, the patient is comfortably posi mental nerves but with significantly less consistency than the
tioned with a bright light directed across the side of the face so supraorbital nerve. Facial muscles other then the orbicularis
that sharp shadows are cast by the facial structures to aid in vi oculi do not typically yield a consistent blink response.
sualizing muscle contraction. The current intensity is slowly in Because of the time resolution of the electrodiagnostic equip
creased until a minimal twitch of a facial muscle is observed. ment, it is possible to resolve both the early ipsilateral response
The current is recorded and compared with a similar procedure (Rl) and the later bilateral response (R2) (Fig. 6-7). By assess
for the unaffected side. The muscles usually observed for this ing the presence, absence, or delay of various components of
minimal twitch are the orbicularis oris and orbicularis oculi. Of the blink reflex, it is possible with some assurance to localize
course, any other muscle may be used. the lesion's presumed site. Both central nervous system and pe
Instrumentation Parameters. Facial muscle CMAPs are ripheral nerve lesion affecting the supraorbital and facial
considerably smaller than those obtained in the limbs and thus nerves can be investigated with this technique.
require a sensitivity of about 200-1,000 !lV/div. The latency is Recording Electrodes. The most efficient manner to re
rather short to the CMAP's onset necessitating a sweep speed of cord the blink reflex is using two channels to detect the three
about 1-2 ms/div. Filter settings are the same as those used for responses generated with stimulation of one supraorbital
median nerve motor studies. Stimulator parameters are noted nerve, specifically, the early ipsilateral Rl and the bilateral de
above. layed R2.113 The ipsilateral E-I to stimulation records two ip- .
Reference Values. Stimulation of the facial nerve anterior silateral facial nerve responses, R 1 and R2. The contralateral
to the ear lobe yields a mean onset latency of 3.57 ± 0.35 ms E-] only records its orbicularis oculi R2. It is also possible to
(2.8-4.1 ms). Postauricular stimulation generates a mean onset record the blink reflex with only one channel, but more stimuli
latency of 3.88 ± 0.36 ms (3.2-4.4 ms).141 When comparing are required.
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 133
Lt. At.
1. R1 2. Ipsilateral R2
----T.----~-
,-I
,LatenCY
I
,•
--------- ----
Duration
-~--------
I
I
_I
A""lItude
Figure 6-7. Blink reflex pathway. The afferent impulse traverses the supraorbital nerve and then enters the pons to divide into a rostral and
caudal pathway. The rostral fibers synapse in the principal sensory nucleus and then descend to synapse with the facial nucleus. The fibers not con
necting with the principal sensory nucleus descend in the lateral aspect of the medulla to then send a contralateral and ipsilateral group of fibers
rostrally to synapse with both the left and right facial nucleus. The facial nerve then conveys the initial ipsilateral and shorter pathway to generate
the RI while the longer bilateral pathway produces the two R2 waveforms. (From Kimura J: Electrodiagnosis in Diseases of Nerve and Muscle:
Principles and Practice. Philadelphia, F.A. Davis, 1989, with permission.)
E-1. Two E-l electrodes are located bilaterally on the pa peripheral nerves are recommended. The current intensity of the
tient. Each is positioned as if one is perfonning a facial nerve stimulator is slowly increased until stable, reproducible. and
study to the orbicularis oculi (Fig. 6-8). maximal Rl and R2 responses are obtained. Because the blink
E-2. There are a number of positions one may choose for E-2. reflex involves a multisynaptic pathway, there is some variabil
It is possible to locate E-2 on the temporal region bilaterallyl25 or ity between successive activations of the supraorbital nerve (es
just superior to the nasalis muscle (Fig. 6-8).141 One can also use pecially with respect to the R2) and at least 8-10 responses
a single E-l electrode placed on the tip of the nose and using a should be elicited with the shortest used for measurement.
"jumper" cable connect it to both E-2 ports on the instrument's Following completion of the study on one side, the contralateral
amplifier, i.e., a common reference for both channels. side is stimulated and responses recorded. Care should be exer
Ground. The ground electrode can be placed on the chin, cised at all times as it is easy to concentrate on the CRT screen
forehead, or cheek. and allow the cathode to slip inferiorly into the patient's eye.
Stimulation. The cathode is positioned directly over the A particularly annoying problem during blink reflex studies
supraorbital notch, Le., the supraorbital nerve (Fig. 6-8). With is that of stimulus artifact that can obscure the Rl response. To
the cathode in this location, the anode is directed superiorly and minimize stimulus artifact production in the face it is crucial to
laterally. It is important not to rotate the anode too far medially remove all makeup, facial oils, and perspiration. This needs to
as the contralateral supraorbital nerve will become activated be accomplished for the entire face and not just around the stim
through anodal break excitation, thus producing bilateral R 1 re ulus site as current from the stimulator will follow the path of
sponses and confusing the diagnostic utility of the blink reflex. least resistance and may still arrive at the electrodes prior to the
It may be necessary to rotate the anode about the cathode to op response, resulting in possible Rl contamination. Attention to
timize the effects of stimulus artifact, which can be a problem detail is especially important in attempting to generate optimal
because of the close association between the cathode and blink reflex responses.
recording electrode. As long as the above caution is kept in Instrumentation Parameters. The R 1 and R2 response is
mind regarding anodal break excitation. there should be no dif relatively small and requires a sensitivity of 50-200 J..l.V/div. The
ficulty with anode rotation. The stimulation site may be some delayed R2 necessitates a sweep speed of 10 ms/div. Filter set
what uncomfortable for patients and a slow stimulus rate of 1 tings are those used for routine motor studies.
Hz is preferable. Additionally. the stimulator prongs should rest Reference Values. Reference values are provided for both
lightly on the supraorbital nerve as this is a rather sensitive the ipsilateral Rl and R2. as well as the contralateral R2 (Table
structure. Stimulator parameters similar to those used for other 6-4). Because of the variability of the responses, three standard
234 - PART II BASIC AND ADVANCED TECHNIQUES
present. 125 On the other hand, should the RID ratio fall below
the expected reference values D is prolonged, implying an ab
normality of the facial nerve.
The same recording and instrumentation parameters can be
used for recording the cornea reDex. 99,132 The stimulation is
easiest done electrically with a cotton thread soaked in saUne
and positioned on the sclera with anode as a surface electrode
near the eye. The main difference from the blink reflex is that
the afferent arc consists of thin (A-delta) fibers with a slow con
duction. The Rl is normally not present and a bilateral response
of 35--50 ms is expected. It is also possible to measure reflexes
limited to the sensory and motor part of the trigeminal nerve
itself. This can be done by eliciting the masseter tendon reflex
by tapping on the chin with a reflex hammer and recording the
responses of the masseter muscle bilaterally with surface elec
trodes. The advantage of this technique in comparison to the
clinical examination is that unilateral absence or delay of the
reflex can be shown. 166 The last reflex is the masseter in
hibitory reDex. The mentalis nerve is stimulated on the left and
right with surface electrodes and recording is done bilaterally
on the masseter with surface electrodes while maximally
~1wt5
clenching the jaws, After unilateral stimulation, two phases of
EMG interruption (silent period) on both sides occur at 10--15
and 40-50 ms latencies, respectively,
Gd
Gd
Cranial Nerve XI (Spinal Accessory Nerve)
Figure 6-8. Blink reflex stimulation. Stimulation (S) of the right The cervical portion of the eleventh cranial or spinal acces
supraorbital nerve that can usually be palpated in the supraorbital sory nerve originates from cervical levels CI-C5.90 Individual
notch. Bilateral recording from the orbicularis oculi with E-I (R.) and nerve rootlets from these cervical segments proceed superiorly,
E-2 (R r ) electrodes positioned for optimal recording of the blink reflex fusing with each sequentially rostral segment until the spinal
responses. (From Ma OM, Uveson JA: Nerve Conduction Handbook. accessory nerve trunk is formed. It continues to course rostral
Philadelphia, F.A Davis, 1983, with permission.) ward entering the cranium through the foramen magnum. While
intracranial, this nerve joins with nerve fibers arising from the
tenth cranial nerve to exit the skull by way of the jugular fora
deviations are used to compute reference values. Temperature is men. Once extracranial, the spinal accessory nerve separates
not routinely measured as the face is usually quite warm. from the tenth-nerve fibers to descend into the neck to innervate
Distance is inconsequential in this study and therefore the the sternocleidomastoid and trapezius muscles. The spinal ac
above-noted anatomic landmarks are used. One can also com cessory nerve is joined by additional nerve fibers from cervical
bine information from the facial and trigeminal nerves to arrive segments CI-C4 via a communication with the cervical plexus
at an optimal ratio of latencies to the orbicularis oculi muscle. while in the neck region. These fibers preferentially innervate
Specifically, the indirect facial response through supraorbital the trapezius muscle after joining the spinal accessory nerve.
nerve excitation RI (R) is divided by the facial nerve latency to After innervating the sternocleidomastoid muscle, the spinal ac
direct activation of the facial nerve (D) to arrive at RID (Table cessory nerve is superficial just posterior to the posterior border
6-4). If RID exceeds the normal limits because R 1 is prolonged of this muscle at approximately the muscle's mid-point. The
but D is normal, a lesion involving the trigeminal nerve is likely nerve then continues distally to innervate the trapezius muscle.
The superficial location of the spinal accessory nerve posterior
Table 6·4. Blink Reflex l25 to the sternocleidomastoid muscle allows easy access to stimu
lation. As for previous NCSs, a technique using surface stimula
Latency (ms) Amplitude (mY)
tion and recording is preferred.
Ipsilateral R I 10.6 ± 0.8; < 13.1 a.l8t 0.23 Reconting Electrodes. E-1. A surface E-I electrode is lo
Ipsilateral R2 31.3 ± 3.33; < 41.0 0.53 ± 0.24 cated on the trapezius muscle approximately 5 cm lateral to the
C7 spinous process on a line between this structure and the
Contralateral R2 31.6 ± 3.78; < 43.0 0.49 ± 0.24
acromion.
UR;RI 1.2 E-2. This electrode is located over a lower thoracic spinous
UR:S;R2 5.0 process. One may also position this electrode on the acromion.
Ul:RlR;R2 8.0 Ground. Althougb one investigator recommends that
ground be located on the acromion,141 positioning it between the
RID 2.6--4.6 stimulus and E-l is preferred.
UR,left-right difference for shortest R I latencies; UR:S,left-right difference for Stimulation. The cathode is located approximately 1-2 cm
R2 responses simultaneously obtained for a particular stimulus; UL:RlR, R2 dif posterior to the posterior margin of the sternocleidomastoid
ferences for the same side obtained with opposite-side stimuli, e.g., R2 latency
on the right obtained with right-sided stimulation subtracted from R2 latency muscle mid-way between the mastoid process and the supraster
on the right obtained with left-sided stimulation; RID, RI divided by direct facial nal notch. This location approximates the superior margin of the
nerve response. thyroid cartilage. The anode is directed superior to the cathode.
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 235
Both cathode and anode should be maintained posterior to the of distal segment conduction by providing a smaller standard
sternocleidomastoid muscle as anterior placement may activate deviation and tighter normal range than distal latencies for both
the brachial plexus or phrenic nerve. If the brachial plexus is ac motor and sensory studies. 110.129 For example, let us assume that
tivated, depolarization of the supraspinatus muscle may be mis two individuals have a DML for their right median nerve of 4.0
taken for the trapezius muscle response because of its close ms. This DML would be considered normal by most practition
proximity. When the spinal accessory nerve is excited, the prac ers. There may be diagnostic significance, however, in this
titioner should observe contraction of the trapezius muscle re DML if one person had a forearm conduction velocity of 65 mls
sulting in shrugging of the shoulder ipsilateral to the side of compared to the other subject with a forearm NCV of 52 mls as
stimulation. suming the DML is measured over an 8-cm segment in both in
Instrumentation Parameters. The relatively short distance dividuals. The respective RLs would be 2.8 ms and 2.5 ms. The
between the stimulus and recording sites requires a sweep speed implication in these findings is that the comparative difference
between I and 2 ms/div. Other than sweep speed, routine motor between the predicted and actual DML is larger for the person
nerve conduction study parameters are used. with a forearm NCV of 65 mls. This suggests that the distal seg
Reference Values. The spinal accessory nerve should nor ment of nerve for the subject with a forearm NCV of 65 mls is
mally generate an onset latency of 1.8-3.0 ms. 28 This is an im conducting slower than for the individual with the lower proxi
portant technique to master because spinal accessory nerve mal NCV. The question then arises as to possible pathology af
injuries are common and this technique can be quite productive fecting the distal segment of nerve with the larger RL.
when performing repetitive nerve stimulation in neuromuscular Normative data are available for both median and ulnar nerves
junction disorders or following lesions due to surgical proce for motor and sensory studies (Table 6-5). Unfortunately, the
dures of the neck. clinical utility of the RL has only been examined in a limited
number of patients and needs further study to assess its true
clinical applicability. 110.129
MISCELLANEOUS TECHNIQUES
COLLISION TECHNIQUE
A number of specialized nerve conduction techniques may be
of clinical assistance under certain circumstances. Occasionally, Most routine studies excite the distal portions of peripheral
alternative methods may help to define a particularly challenging nerves where they are separated from neighboring nerves by
diagnosis. The residual latency, collision study, and refractory sufficient distances to allow selective neural excitation. Unless
period are electrophysiologic techniques that electrodiagnostic one is using large current intensities and durations, a single
medicine practitioners should be capable of performing. nerve can usually be examined. The selective delivery of a de
polarizing pulse becomes much more difficult when attempting
RESIDUAL LATENCY to excite nerves in a proximal location such as the axilla. The
close proximity of the median and ulnar nerves often precludes
It is weB known that nerve conduction velocities in proximal exciting either one individually. The result is a significant depo
nerve segments are greater than in the distal portion of the larization of multiple upper limb muscles with occasional over
nerve. Because NCV in general is directly proportional to axon lap of distal electrical responses. For example, suppose a
diameter, slowing is attributed to tapering of the nerve as it selective recording from the median-innervated thenar muscles
reaches the distal regions of the limb.40·41 Consequently, in an is the desired goal. This should pose no particular problem
upper limb a nerve cannot be expected to conduct with the same when activating the median nerve at the wrist or elbow provided
velocity within a few centimeters of the nerve's termination excessive current intensities are not used. The difficulty arises if
compared to a region in the forearm. However, if one were to a proximal conduction velocity of the median nerve is desired,
apply the forearm conduction velocity to the distance over i.e., axilla to elbow segment. It is highly probable that axillary
which the distal motor latency were measured, a time difference stimulation will result in coactivation of both the median and
between the predicted and observed distal motor latency would ulnar nerves as well as possibly the radial nerve. The recorded
arise. This difference is referred to as the residual latency CMAP from the thenar muscles may not be a true reflection of
(RL). I 10.129 The concept of residual latency is perhaps best un the activity arising solely from the median-innervated thenar
derstood by using an example. Let us suppose a median nerve muscles. There is a good chance that the observed CMAP re
conducts with a velocity of 60 mls in the forearm and has a flects not only the median-innervated thenar muscle electrical
distal motor latency of 4.0 ms over an 8-cm segment. If one activity, but may also contain volume-conducted potentials from
were to assume that the NCV over the distal 8 cm also was 60
mis, then the predicted distal motor latency would be 1.3 ms (60 Table 6-5. Residual Latency (ms)II0.119
mls = 8 cmIDML; DML = 1.3 ms). The difference between the
predicted and observed DMLs, residual latency, is 2.7 ms. In Control Neuropathy
other words, there is a 2.7-ms discrepancy between the observed Ulnar nerve (S) 1.3 ± 0.3 (0.8-1.8) 2A ± 1.0 (2.0-3.0)
and calculated DML. This same principle may be applied to
Ulnar nerve (M) 1.4 ± 0.8 (1.0-1.9) 3.0 ± 0.8 (2.7-3.3)
sensory as well as motor nerves only using the distal latency (to
initial takeoff of the SNAP) as opposed to the DML. A general Median nerve (S) 1.3 ± 0.3 (0.8-1.8) 3.4 ± 1.2 (2.0-4.0)
formula may be used to determine the residual latency: RL = Median nerve (M) I.S ± 0.3 (1.0-2.0) 3.3 ± 1.0 (2.7-3.8)
DL - (cathode to E-l distance in mmlforearm NCV in mmlms). Median nerve (M)t 1.9 ± 0.2 (1.4-2.S)
The proposed diagnostic utility of residual latencies is to
S, Sensory RL; M. motor RL
compare the distal aspect of the nerve segment to the more t Median nerve RL (from Kraft GH, Halvorson GA: Median nerve residual la
proximal aspect of the same nerve. Residual latency determina tency: normal value and use in diagnosis of carpal tunnel syndrome. Arch Phys
tions should theoretically eliminate the intersubject variability Med Rehabil 1983;6-'4: 221-226.)
the neighboring ulnar-innervated hand intrinsic muscles such as solely from axillary excitation. It is then possible to calculate
the first dorsal interosseous (FDI) and adductor pollicis (AP). If the conduction velocity from this segment involving only the
the action potentials conducting in the median nerve fibers median nerve fibers. Delaying the axillary stimulation slightly
reach the thenar eminence first, then a correct DML is detected compared to that delivered at the wrist results in slightly more
with an appropriate proximal median nerve conduction velocity. separation between the two recorded CMAPs should this be
The amplitude, however, may be erroneous as it reflects activity necessary in selected cases. The collision of the two ind~ced
from both median- and ulnar-innervated muscles. Depending ulnar nerve impulses is why the method is known as a collision
upon phase interactions of the two potentials, the amplitude technique. Of course, the principle of collision can be used for
may be larger or smaller than anticipated, although it is typi any nerve and not just the ulnar nerve. Additionally, applying
cally larger. This situation would change if there was preferen collision principles and appropriately separated stimulus inter
tial slowing of the median nerve conduction across the wrist vals, one also can examine slower-conducting nerve fibers by
segment; the fastest-conducting fibers would be prevented from selectively blocking the faster-conducting axons. The collision
reaching the thenar muscles either by a conduction block or technique also may be of assistance in selectively blocking con
axonal loss. duction in anomalous neural conducting pathways.76.SS.100.IS7
Stimulation of the median nerve at the wrist and elbow in the
above case would accurately reflect this slowing, yielding both REFRACTORY PERIOD
a prolonged DML and lower conduction velocity. Remember,
even though the distal segment is supposedly removed from Immediately following depolarization, that portion of an
nerve conduction velocity determinations for the elbow-to-wrist axon is completely inexcitable and cannot generate an action
segment, if the fastest fibers never reach the muscle, then the potential for a brief time. Within the next several milliseconds,
onset latency of the slower-conducting fibers determines the the axonal membrane becomes relatively excitable and can pro
CMAP's onset latencies for all stimulus sites and hence the re duce an action potential, eventually returning to its resting
spective conduction velocities. IIS When performing the axillary state. It is possible to investigate the axon's membranous elec
stimulation, it is highly likely that the coactivated ulnar nerve trical properties by delivering two successive stimuli with vary
impulses will reach the hand intrinsic muscles prior to the ing interstimulus intervals. By convention, the first excitation
median nerve because of its slowing at the wrist. If the instru pulse is referred to as the conditioning stimulus. The second
ment's sensitivity is relatively low or the ulnar nerve's nearby or test stimulus is then delivered at a predetermined interval.
muscles happen to coincidentally align their motor point with This terminology is used because the first excitation conditions
E-l, then an initial positive deflection is not observed and one the nerve, whereas the second depolarization tests the effect of
may erroneously conclude that the observed CMAP's negative the first stimulus on the nerve's voltage-dependent ion gates.
onset latency reflects median nerve conduction. The prolonged That time period after the conditioning excitation during which
antecubital median nerve latency combined with the shortened a test stimulus fails to evoke a response is referred to as the ab
axillary median nerve latency results in a rather fast axilla-to solute refractory period. A depolarization pulse, irrespective
elbow conduction velocity that is not a true reflection of the of strength, is incapable of inducing an action potential. At
median nerve's proximal neural segment conduction. Should a some point in time a test response can generate an action po
positive deflection be observed with axillary excitation, it is tential but it is smaller than the conditioning response and de
clear that one is not observing median nerve fiber excitation and layed in latency compared to the anticipated time of
no conduction velocity should be attempted. Should the positive observation with respect to when the nerve is activated. At
deflection be used to compute the conduction velocity, a similar some longer interval following the conditioning stimulus, the
situation to that described above results. The question remains, test response again resembles the conditioning response re
is it possible to examine the proximal segment of the median garding appearance latency and amplitude. That segment of
nerve without contamination from the ulnar nerve? time following the absolute refractory period and detection of a
The proximal segment of the median nerve can be investi test response identical to the conditioning potential is known as
gated by using coactivation of both the median and ulnar nerves the relative refractory time.
at appropriately separated time or distance intervals. If a supra The proposed physiologic mechanism generating the two as
maximal stimulus is delivered to the axilla and coincidentally at pects of reduced neural excitability is believed to be sodium in
the wrist to only the ulnar nerve, an interesting electrical event activation. 139 Recall that immediately following activation of
ensues. An early volume-conducted response from the ulnar-in voltage-dependent sodium gates, action potential generation,
nervated hand intrinsic muscles is recorded from E-I located on the same voltage-dependent gates close, thus significantly re
the thenar eminence secondary to ulnar nerve stimulation at the ducing sodium conductance. The closure of sodium gates is an
wrist. Because the origin of this CMAP is known to arise from intrinsic property of these proteinaceous channels and they
the ulnar nerve, it is ignored. The impulse induced at the wrist remain closed for a finite period of time irrespective of an addi
also conducts proximally along the ulnar nerve. Recall that the tional depolarizing stimulus.
axillary impulse is traveling distally in both the ulnar and It is important to remember that sodium channel opening is
median nerves. At approximately the mid-arm level, the proxi dependent upon a voltage difference and that their opening
mally and distally propagating ulnar impulses collide and anni spans a finite time period. If the voltage applied to a nerve is
hilate each other. The median nerve impulse, however, slowly and progressively increased, it is possible to exceed the
continues distally to reach the thenar eminence generating a threshold level at which an action potential is generated. This
pure median nerve response. Because the median nerve action occurs because only a few sodium channels are induced to open
potentials originated in the axilla, the CMAP produced is suffi at a time. As new channels are opened at a slightly greater volt
ciently delayed in time so as to not overlap with the volume age difference, the previously opened channels are closed or be
conducted CMAP generated at the wrist by ulnar nerve ginning to close. The process of exceeding the nerve's threshold
excitation. The end result is a pure median nerve CMAP arising without action potential production is called accommodation.
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 237
On the other hand, just after the passage of an action poten period. 4,151 People with motor neuron diseases also display pro
tial, sodium gate closure or sodium inactivation renders the longed refractory periods.
membrane incapable of sustaining action potential induction. A limited number of investigations have been performed to
This time of complete inexcitability during which the sodium determine the clinical utility of neural refractory characteristics
gates are closed accounts for the absolute refractory period. in disease states, The relative ease with which refractory periods
Sodium gate closure and subsequent opening occur over a can be applied to the peripheral nervous system with commer
finite time in that the gates do not all open and close simultane cially available equipment should allow investigators to pursue
ously, i.e., this process occurs over a little less than I ms. As this area in the future. Direct muscle stimulation reveals that in
more and more of these voltage-dependent gates begin to re muscle suffering from various forms of muscular dystrophy, the
cover from their mandatory inexcitable phase, at some point absolute and relative refractory periods are reduced compared
there is enough potentially excitable gates to again generate an to normal. 161 Denervated muscle, on the other hand, reveals a
action potential, but one of less magnitude that takes longer to prolongation in both the absolute and relative refractory times.
generate the amount of current required to excite the next node The pathophysiology underlying these changes remains to be
of Ranvier, Le., propagation. A stimulus of sufficient magni completely elucidated.
tude above the resting state's previous supramaximallevel can Refractory period observations have been performed in ani
induce a synchronous opening of the available sodium gates to mals for quite some time but this requires removal of the nerve.
produce a relatively smaJl and delayed action potential. With As this is unacceptable for human studies, a simple yet elegant
progressively longer interstimulus intervals, more and more methodology has been developed that can be performed rou
sodium gates capable of being excited become available. tinely by most practitioners with the appropriate equipment.
Correspondingly, less and less current is required to generate The actual methodology requires that one's instrument have the
an action potential. The increasing number of potential1y ex capability of delivering two stimuli with varying interstimulus
citable sodium gates allows threshold to be reached progres intervals. With this type of stimulus delivery, it is relatively
sively earlier. Also, the larger number of sodium gates allows straightforward to examine either mixed or pure sensory nerves.
more current to flow, which in turn produces a larger action po Mixed Nerve Studies. To perform mixed nerve refractory
tential until the test and conditioning waveforms are the same. period measurements, the technique of Gilliatt and Willison 75
The time between sufficient sodium gates to just generate an can be used.
action potential and enough to produce similar conditioning Recording Electrodes. E-I. The E-l surface recording
and test responses is the relative refractory period. Following electrode is located over the median nerve just proximal to the
the relative refractory period is a supernormal period during antecubital fossa.
which the propagating test stimulus conducts at a velocity E-2. A surface E-2 electrode is positioned over the insertion
somewhat greater than normalJ5 of the deltoid on the lateral aspect of the arm.
Although the above description is correct, the actual tech Ground Electrode. The ground electrode should be secured
nique requires propagated action potentials to be recorded at a to the forearm just distal to E-l.
distance from their production site. In other words, there may Stimulation. The median nerve is excited at the wrist in a
be a time where an action potential may be produced locally at similar manner to that used for routine median nerve motor
the region of axonal membrane depolarization but it is of insuf studies except the cathode is located proximal, i.e., pointing
ficient magnitude to result in propagation. Indeed, this is found toward E-l. A pulse duration of 0.2 ms may be used. Initially, a
to be the case and the time period between the absolute refrac minimum threshold and single supramaximal stimulus is deliv
tory period and the observation of a small and delayed propa ered. The supramaximal response is then used to determine the
gating action potential is known as the critical interval of optimal recording electrode position for the mixed median
conduction.213 Of course, this time interval can best be mea nerve waveform.
sured with near-nerve microelectrodes. For practical purposes, An instrument with the capability of delivering sequential
however, the absolute and relative refractory periods can be pair of stimuli from the same cathode at predetermined inter
conceptualized depending upon the detection or lack of a test stimulus intervals is required. Specifically, it is helpful if inter
stimulus following a conditioning pulse. stimulus intervals between two successive stimuli of 0.1 ms can
be delivered. A stimulus exceeding the suprathreshold magni
Clinical Utility tude 4-6 times is delivered at 0.1 ms intervals following the
By investigating the refractory periods of peripheral nerves, it conditioning stimulus to determine the absolute refractory
is possible to assess the effects of various disease states. In ex period.
perimental demyelinating diseases of the peripheral nervous Once the absolute refractory period is determined it is possi
system, experimental allergic neuritis, and diphtheria-induced ble to determine the relative refractory period. Beginning at the
demyelination, the refractory periods are significantly in point when the second response was first detected with the max
creased. 31 •32.179 In demyelination secondary to lysophosphatidyl imal stimulus, a response is attempted at the next O.l-ms inter
choline, refractory periods demonstrated a better correlation val. In this instance, however, only enough current is used to
with histologic findings than did conduction velocities. 204 Of in produce a detectable response. This procedure continues at in
terest is the finding of abnormal refractory periods in patients creasing intervals until the originally determined baseline stim
with multiple sclerosis, suggesting that peripheral nervous ulus is reached. That stimulus interval between a just visible
system membrane characteristics may be altered in this response at 4-6 times stimulus threshold to the resting value de
disease. IOI Also, in patients with various peripheral neurop fines the relative refractory period. Continuing to increase the
athies, the relative refractory period appeared to be a more sen interstimulus interval and measuring minimum stimulus excita
sitive indicator of abnormality involving neural structures than tion levels allows one to calculate the supranormal period. The
the absolute refractory period. On the other hand, hypokalemia time when the original threshold value is required to just elicit a
has been found to actually shorten the relative refractory potential defines the cessation of supranormality.
238 - PART II BASIC AND ADVANCED TECHNIQUES
It is important to note that delivery of the high-intensity cur Refractory Periods in Muscle
rents/voltages required to properly study the refractory periods In addition to measuring the refractory periods in nerve, it is
can be quite uncomfortable and not tolerated by all patients. also possible to determine the absolute and relative refractory
Additionally, proper skin site preparation with commercially periods in muscle fibers. Using the paired stimulation tech
available abrasives to reduce impedance is recommended. nique, direct muscle fiber stimulation can be performed while
Instrumentation Parameters. A sweep speed of I msldiv and recording from single muscle fibers. 161.206 The studies reveal ~hat
amplifier sensitivity of 20 J.l. V/div should suffice for most persons. the absolute refractory period in muscle with a stimulation in
Filter settings of 10-20 Hz to 2 kHz will yield detectable responses. tensity 25-35% above the conditioning stimulus is 4.12 ± 1.73
Reference Values. The absolute refractory period measured ms (2.69-8.13 ms). The relative refractory period for muscle
with above technique was found to be less than 0.6-0.7 ms.1 5 ln fibers is 5.99 ± 2.7 ms (2.88-12.40 ms). A supranormal period
other words, the second potential was first observed at an inter also can be observed at 10.19 ± 3.2 ms (4.86-15.7 ms). As for
stimulus interval of 0.6-0.7 ms. The relative refractory period nerve, the waveforms in the relative refractory period are
lasted between 2.5 and 3.5 ms. Following the relative refractory smaller and demonstrate an increase in the rise time and a
period, a supranormal time interval extended for 5-8 ms. longer total duration.
the ventral hom of the spinal cord to synapse with inhibitory in
temeurons known as Renshaw cells (Fig. 6-10). Renshaw cell
activation tends to suppress activation of motor neurons they
synapse with by generating inhibitory presynaptic potentials
(IPSPS).45,198 As an antidromic impulse traverses the axon
toward the ventral hom, the axon collateral conveys an action
potential to the Renshaw cell, which in turn tends to suppress
the motor neurons it synapses with.
The final level of excitability of the motor neuron pool, there
fore, is dependent upon multiple excitatory and inhibitory influ
ences from various aspects of the central and peripheral nervous
systems. l76•m When a mixed peripheral nerve is stimulated with
a supramaximal stimulus, the large number of antidromic motor
action potentials enter the ventral horn to find the resting mem
brane potentials of their respective motor neurons' soma at vari
ous levels. Whether a particular motor neuron generates a
recurrent discharge depends upon the level of depolarization of
the soma and its dendrites. Let us assume that the resting mem
brane potential of the axon hillock favors depolarization of this
Figure 6-10. Renshaw cell activation. The alpha motor neurons region, thus facilitating action potential propagation into the
possess a recurrent collateral portion of the axon just distal to the motor neuron soma from an antidromically induced impulse.
axon hillock, which extends to inhibitory interneurons known as This action potential then propagates into not only the main por
Renshaw cells (R). Once the recurrent collaterals activate the tion of the soma but also into the various expanses of the alpha
Renshaw cell, it in turn synapses with alpha motor neurons to gener motor neuron's dendrites (Fig. 6-11). By the time the depolar
ate inhibitory postsynaptic potentials (-), which suppress firing of ization has reached the distal portions of the dendrites, the axon
these neurons. hillock has undergone repolarization and is no longer in its re
fractory period (about 1 ms).46,47.48 The negative sinks of the den
drites are causing the ions surrounding the axon hillock to serve
other dendrites occur over the motor neuron's soma and gener as a current source for the dendritic depolarization. This tends
ate either excitatory or inhibitory impulses. 11,198 The net summa to alter the ionic distribution around the axon hillock by de
tion of excitatory and inhibitory potentials determines the creasing the positive charge on its surface. The transmembrane
overall excitability of the motor neuron and whether it generates voltage alteration may induce an action potential to occur at this
a depolarization impulse of sufficient magnitude to excite the portion of the axon, thus generating the recurrent backfiring of
axon hillock region producing a propagating action potential. the motor neuron begetting the subsequently observed F-wave
Within a short distance distal to the axon hillock, a number of (Fig. 6-11). The critical time period or "window of opportunity"
spinal motor neurons possess a recurrent coUateral, which is a between repoiarization of the axon hillock coinciding with
neural branch given off from the axon that proceeds back into soma/dendritic local circuit currents is about 10-30 IlS.195
A B c
Figure 6-1 I. Motor neuron "backfiring." Proposed mechanism of the so-called alpha motor neuron's "backfiring" to generate an F-wave. A,
Initially the action potential enters the axon hillock region and begins depolarization of the anterior horn cell's soma. Solid arrows are the sodium
ions carrying the inwardly directed current while dotted arrows are the internally directed current. B, This depolarization then extends into the
dendritic extensions of the motor neuron while the axon hillock is refractory. Because the motor neuron's dendrites are depolarizing similar to an
unmyelinated nerve, i.e., continuous and not saltatory, the axon hillock exits its refractory period while depolarization is still occurring in the den
drites. The dendrites regions of depolarization act as a current sink while the sodium ions surrounding the axon hillock serve as a current source.
C.A source current from the region of the axon hillock alters the transmembrane voltage (less pOSitive extracellular) and this tends to depolarize
the axon hillock generating an impulse propagating toward the periphery, i.e., an F-wave is then detected.
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 241
Should the soma's membrane be depolarized to an extent ex the proximal segment of the peripheral nervous system or depo
ceeding that previously described, it and the dendrites will de larize the soma preventing repolarization. 81 ,J36 Finally, there is a
polarize comparatively early and generate a local circuit current greater chance of shortening the depolarization time of the soma
during the refractory period of the axon hillock. This situation in smaller motor neurons, possibly because of suprasegmental
results in the failure of F-wave production. On the other hand, influences lowering the resting membrane threshold of the
the transition between the myelinated portion of the axon and smaller motor neuron soma. IO•IS2 It is known that smaller motor
the axon hillock does not favor conduction into the soma be neurons fire at lower thresholds than larger motor neurons giving
cause the current distribution is diluted over the nonmyelinated rise to the orderly recruitment of motor neurons, i.e., the
portion of the axon hillock. In other words, the current distribu Hennemann size principle.91 ,92 Smaller motor neurons, therefore,
tion is not concentrated at a node of Ranvier but spread out over may have resting membrane levels closer to the depolarization
the surface of the axon hillock. If the resting membrane poten threshold compared to larger ones. This may be an important
tial of the axon hillock is relatively hyperpolarized because of mechanism of recurrent discharge inhibition in smaller motor
segmental and suprasegmental influences, action potentials will neurons because recurrent collaterals are found in approximately
not cross this region to invade the soma and dendrites. In this 70-80% of them, leaving 20-30% without the possibility of re
case, an F-wave is not produced. The reason only a small current inhibition. l94 Should the threshold be lowered in smaller
number of F-waves are observed, therefore, is because of the re motor neurons, they will depolarize rather quickly, generating an
quired convergence of a number of excitatory and inhibitory in action potential in the soma-dendrite region and creating a local
fluences favoring action potential conduction across the axon circuit current incapable of exciting the axon hillock because it is
hillock with an appropriate temporal delay across the soma and still refractory. These three mechanisms or some combination
dendrites favoring reactivation of the axon hillock. This situa may be the reason why there is preferential activation of rela
tion changes from moment to moment, thereby resulting in a tively larger motor neurons generating the detectable F-waves.
different subpopulation of motor neurons amenable to depolar
ization by an antidromic means with each ensuing stimulus. Diagnostic F-Wave Techniques
The variable latency of sequentially elicited F-waves may be A number of investigators have developed several interesting
understood if one considers the motor neuron population pro methodologies in which the F-wave can be used diagnostically.
ducing the individual F-waves. Investigations in both humans The basic parameter used by all investigators is the F-wave la
and animals reveal that there is a greater chance of F-waves tency. Because sequential F-wave latencies are variable, innova
being generated by comparatively larger motor neurons. 81 ,124.169 tive strategies have been developed to address this potential
Larger motor neurons give rise to relatively large axons that problem. Some of the techniques discussed include mean F
have faster conduction velocities than smaller axons from the wave latencies over various body segments, latency ranges, F
smaller motor neurons. Also, larger motor neurons innervate wave conduction velocities, and F-wave latency ratios. Only a
more muscle fibers, thus creating larger motor units with larger few investigations, however, have addressed amplitude for diag
magnitude F-waves. The resultant F-waves detected, therefore, nostic purposes.
preferentially arise from the faster-conducting axons that have a An F-wave may be obtained from essentially any muscle pro
certain diameter range. This diameter distribution yields axons vided a supramaximal stimulation is used and the amplifier's
conveying F-waves with slightly different conduction velocities. sensitivity is sufficient to detect the response. Because of the
Since there are very few F-waves that repeat with sequential relative long duration of the CMAP the F-wave may be un
stimulation (19.5%), a large number of different F-waves are recordable in short nerve segments. The amplifier should be set
observed from the available pool of motor neurons. S1 The vari at approximately 100-200 !lV/div to ensure observation of the
able latency of F-waves represents the distribution of conduc F-wave. Of course, a sensitivity of this magnitude does not
tion velocities ofaxons mediating the recurrent responses. permit one to simultaneously observe the entire CMAP. The
Of the 1-2% of motor neurons capable of producing an F rather delayed latency of the F-wave with respect to the CMAP
wave secondary to segmental and suprasegmental inhibitory in requires a sweep speed of 5 ms/div and 10 ms/div in the upper
fluences, one may attempt to understand the preferential bias and lower limbs, respectively. The easiest muscles to record F
toward larger motor neurons generating F-waves. First, there is a waves from are the small intrinsic hand and foot muscles.
greater chance of larger motor neurons, through axon collaterals Because of this, the majority of reference data available pertain
activating Renshaw cells, inhibiting smaller ones.46,SI This is be to the following muscles: abductor pollicis brevis, abductor
cause of the faster conduction velocity of antidromic impulses in digiti minimi. extensor digitorum brevis, and abductor hallucis.
larger axons (bigger motor neurons) reaching the Renshaw cells Routine recording techniques previously described are used. It
before the smaller axons (smaller motor neurons) and exerting a is not necessary to relocate the anode distal to the cathode when
blocking influence on the smaller motor neurons. In a sense, the exciting the nerve as anodal block most likely does not occur.
faster axons compete for optimal levels of resting membrane po When stimulating the nerve, an optimal stimulus rate is 1 Hz or
tentials for recurrent motor neuron excitation with each other, less. ISO
whereas the smaller motor neurons have a reduced chance of Slight contraction of the muscle under investigation can facil
generating an F-wave. Also, it is easier for Renshaw cells to in itate the observation of F-waves should one note a decreased
hibit smaller motor neurons as there is less soma membrane to ability to record them. This is most likely mediated through in
be affected. 47 ,79 Secondly, the afferent fibers of smaller motor creased motor neuron pool excitability. Caution is required
neurons conduct slightly faster than their corresponding motor when attempting to facilitate the F-wave because amplitudes
fibers. These afferent impulses may reach the spinal cord prior to may be increased and an H-reflex (see below) may contaminate
the antidromically excited motor fibers setting up a reflex re the desired responses. The effect of facilitation, however, is not
sponse in which the small motor neuron is reflexively excited. consistent. 195 Although difficult to quantify, a reduction in the
The reflex-induced action potential from the small motor neuron numbers of F-waves following supramaximal stimulation may
would then collide and cancel the antidromic action potential in indicate pathology.
242 - PART II BASIC AND ADVANCED TECHNIQUES
The rationale for attempting to record the F-wave is multifac soleus: 2.8 ± 1.1 ms.59.169.170.171,176.177 The major limiting factor in
torial. Recall that the F-wave is a potential that represents con performing the F chronodispersion technique is that 100 F
duction from the site of stimulation to the motor neuron and waves must be acquired in order to obtain a large distribution of
back to the recording electrode, i.e., both the proximal and latency differences. Patient tolerance and the time required to
distal regions of the peripheral nervous system. As demmi calculate these data are major drawbacks to routinely using this
strated above, it is relatively easy to examine conduction in the technique despite its reported sensitivity to pathology. 170
distal portions of the peripheral nerves. Assessment of proximal Occasionally, one may wish to calculate the F-wave latency
conduction becomes technically more demanding and subject to over a localized proximal segment such as the brachial plexus.
volume conduction effects. The F-wave impulse, however, orig Obviously, stimulating the median or ulnar nerve at the wrist in
inates distally where there is less ambiguity of the nerve ex cludes the entire nerve segment from wrist to spinal cord and
cited; it also is recorded distally, with little interference from back to the muscle. By subtracting the CMAP distal motor la
neighboring muscles. Theoretically, the F-wave appears to be tency to wrist stimulation from the shortest F-wave latency and
the ideal parameter to use to assess proximal conduction. then subtracting an additional 1 ms, a conduction time for the
Although there are a number of limitations regarding the F fastest conducting F-wave from wrist to spinal cord and back to
wave (see below), this concept is generally correct. the wrist is obtained. It is necessary to reduce the conduction
time by I ms because this is believed to represent the turnaround
F-Wave Latency time for motor neuron reactivation in the spinal cord. It is impor
As previously stated, the F-wave latency varies from one tant to note that this presumed I-ms turnaround time has never
stimulus to the next (Fig. 6-9). It is important to record a suffi been documented and obviously presents itself as a potential
cient number of F-waves to ensure analysis of a representative complicating factor in various techniques using this time frame.
sample of the total available pool of motor neurons producing Further, dividing this latency by 2 allows one to determine the
F-waves. The exact number of F-waves necessary to produce a conduction time from wrist to spinal cord, the central conduc
representative number is unknown. The practicality of available tion time. In other words, the equation representing this latency
time for F-wave collection during an electrodiagnostic medicine is: central conduction time =(F-wave latency - DML - I ms)/2.
examination also must be considered. A number of investigators The problem with this method is that a small lesion in a proximal
recommended obtaining between lO and 20 F-waves per stimu portion of the peripheral nervous system could be diluted out
lus site. Although gathering still larger numbers ofF-waves may over the spinal cord to wrist distance, thereby reducing the sensi
yield a few with shorter latencies, the diagnostic utility versus tivity of this technique. An alternative method is to stimulate the
time consumed becomes prohibitive. F-wave reference data are median or ulnar nerve in the axilla and measure the F-wave over
somewhat variable from one investigator to the next not only this comparatively shorter segment. Unfortunately, the CMAP
because of the inherent variability of the response itself, but also and F-wave occur at about the same time, thus obliterating the F
because the latency depends on the stimulus site. As there are wave. A second stimulation applied at the wrist simultaneously
no universally accepted standards with respect to distance be with axillary excitation collides with the orthodromic axillary
tween the cathode and recording electrodes, the F-wave demon impulses permitting detection of the axillary F-wave through a
strates slightly different mean values from one laboratory to the collision technique. 60 A simpler method to examine the proximal
next. For the F-wave latencies reported, the median and ulnar F-wave latency is to stimulate the desired nerve in the axilla 25
nerves are excited just proximal to the distal wrist crease, cm from the sternal notch with the arm abducted 90° and the
whereas the tibial nerve is activated posterior to the superior forearm supinated.97 The shortest F-wave latency from the wrist
margin of the medial malleolus and the peroneal nerve just is then added to the previously obtained CMAP DML from
above the ankle region (Table 6-6). The previous locations of an which is subtracted the axillary CMAP latency multiplied by 2
8 cm standard distance should result in similar mean F-wave la and is called the axillary F-loop latency (AFLL): AFLL = (F
tencies. Recommended side-to-side differences for both short wave + DML) - 2 axillary latency. An axillary F-Ioop latency in
est latency and mean latency are 2.0 ms in the upper limb and excess of 11.0 ms is considered abnormal. 97•240 Because this tech
4.0 ms for lower limb intrinsic muscle studies. 63 In general, F nique involves the fastest F-waves, an attempt was made to in
wave latencies are directly related to height and limb length as crease the sensitivity by averaging 32 F-waves and measuring
anticipated given the length of the neural pathway, but there is the averaged F-wave peak latency and inserting this value into
minimal correlation to age and gender.59.126.176.177 the previously defined AFLL equation. Normal values for the
In the above technique, the shortest F-wave latency may be median and ulnar nerves were reported as 14.12 ± 0.88 ms and
used to determine pathology if a given nerve is injured. The dif 13.97 ± 0.9 ms, respectively.98
ficulty in using the shortest F-wave is that the study is biased
toward one nerve fiber. If there is significant damage to the pe F-Wove Conduction Velocity
ripheral nervous system but one or a few of the fastest-conduct Once the shortest F-wave of a series is obtained, it is possible
ing fibers survive, then a normal study is declared. A more to convert this latency into a conduction velocity. I 15.116 There are
rational approach is to consider the mean value of a group of F two major assumptions involved in using F-wave conduction
waves recorded. 212 The mean onset latency of 10 or more F velocities. The first assumption is that the shortest F-wave is de
waves is believed to be more sensitive than only considering the tected within the limited number of responses obtained, less
fastest F_wave.52.59.98 than 20, and these correspond to the motor fibers producing the
One also may attempt to measure the latencies of a large onset latency for the CMAP detected with distal stimula
number of F-waves, 100 or more, and calculate the time differ tion.13o.242 It has been clearly demonstrated that the shortest F
ence between the shortest and longest F-waves. This technique wave does not always occur within the first 20 potentials, but
has been referred to as F chronodispersion. l69 F chronodisper may require up to 100 or more responsesYi9 The second as
sion reference values for a number of muscles are known: APB: sumption requires an accurate measurement of the conducting
3.6 ± 1.2 ms; ADM: 3.3 ± 1.1 ms; EDB: 6.4 ± 0.8 ms; and pathway traversed by the impulses generating the F-wave. This
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 243
is rather easy for the limb, but the difficulty arises when proxi F-Wave Ratio
mal segments across the brachial or lumbosacral plexi are in Because of the potential for distance measurement errors in
volved. It has been determined in a very limited number of calculating F-wave conduction velocities, an alternative F-wave
anatomic specimens that measuring from the stimulus site, technique was developed that does not involve distance. 49,so It
ankle or popliteal fossa, to the Tl2 spinous process by way of was determined that if the median or ulnar nerve was stimulated
the greater trochanter approximates rather well the true at the elbow region, the time of conduction for the F-wave to the
anatomic length of the tibial nerve. 130 The same anatomic verifi spinal cord was very similar to the latency for direct motor
cation, however, has not been determined for the upper limb. nerve activation from the same site to the muscle, i.e., CMAP
Although F-wave conduction velocities have been criticized be onset latency. In other words, the F ratio is close to unity.
cause of the unnecessary addition of a potentially large error Similar findings were noted for tibial and peroneal nerve stimu
due to less than accurate distance measurements,I30,243 conduc lation while recording from the intrinsic foot muscles (Table 6
tion velocities nevertheless continue to be used. The use of F 6).119,120,121 The equation used to determine F ratios is:
wave conduction velocities has been justified on the basis of
noting that the difference in latencies between stimulating the F ratio = (F-wave latency - CMAP latency - 1 ms)/2
CMAP latency
peroneal nerve at the ankle and knee while recording from the
EDB correspond to the differences in F-wave latencies from or
these two sites, i.e., 6.5 ms and 6.4 ms, respectively. The impli
cation of this finding is that the shortest-latency motor fibers de F ratio = (F-wave latency - CMAP latency) - 1 ms
CMAP latency x 2
termining CMAP onset latency correspond to similar fast fibers
mediating the shortest F_wave,121,124 In calculating F-wave con Although it is possible to calculate F ratios with either more
duction velocities for upper limb examinations, the distance proximal or distal stimulation sites, the variability of data is
from the point of stimulation is measured to the C7 spinous minimal with elbow and popliteal fossa excitation. Motor nerve
process with the arm abducted 90°. The equation used to calcu and F-wave conduction velocities may both be abnormal yet the
late F-wave velocities for both intrinsic hand and foot muscles F ratio can be within normal limits. This suggests that not only
is: are the peripheral nerves conducting slowly over both the distal
and proximal segments, but they are slowed to a similar degree.
F-wave CV (mls) = (distance to Tl2 or C7 in mm) x 2
(F-wave latency CMAP latency - 1 ms) F-Wave Amplitudes and Persistence
Normal values for both upper and lower limb nerves at multi In disorders in which the central excitability of the motor
ple stimulation sites are provided (Table 6_6).123 The F-wave neuron pool is decreased, one could anticipate both a reduced
conduction velocity has been reported to be of value in detect number and smaller amplitude of F-waves. This has been found
ing proximal slowing in various disease states affecting the pe to be the case in patients examined immediately following a
ripheral nervous system. 58,114.1l5 There is some suggestion that unilateral stroke,58 Excitation of the cerebellum also can de
using an averaged F-wave latency to calculate F-wave conduc crease F-wave amplitude and persistence.58,66 On the other hand,
tion velocities may be of greater sensitivity in detecting abnor in patients with chronic myelopathies and spasticity, F-wave
mality compared to the shortest F-wave latency.59.98 A persistence and magnitude are increased commensurate with the
modification of the F-wave chronodispersion using the distrib elevated excitability of the motor neuron pOOPI The latencies
ution of F-wave conduction velocities (F tacheodispersion) is of F-waves in patients with upper motor neuron lesions, how
believed to be a sensitive method of defining peripheral nerve ever, may be prolonged secondary to the unmasking of smaller
conduction abnormalities but more studies are required to fully motor neurons (slower peripheral conduction) while the larger
evaluate this technique. 3o ones are blocked secondary to rapid depolarization. 60,61 It is possible
to calculate the ratio of the F-wave to that of the corresponding process affecting at least the motor aspects of the peripheral ner
CMAP (FIM ratio) in an attempt to measure the amount of the vous system.
motor neuron pool activated. Because of the variability of the F In addition to a mild diffuse peripheral nerve process, a prox
wave amplitude, mean amplitudes calculated from a series of F imal lesion in the neighborhood of the brachial plexus or more
waves appears to be the most reasonable method. 5 I.5s.62.66.67 The rostral (root level) may be amenable to diagnosis by the use of
clinical utility of F/M measurements in routine electrodiagnos F-waves. These "proximal" lesions are limited to two disorders,
tic medicine examinations remains to be demonstrated. and under specific conditions. The first is Guillain-Barre syn
drome, in which a reduced number or absence of F-waves may
F-Wave Clinical Utility be observed secondary to an early and significant blockade of
The clinical utility of various F-wave techniques is by no action potential propagation across the root region. 171 This may
means universally agreed upon by even a minority of practition be the only abnormality noted early on in some but not all pa
ers.65.185 As a result, the authors will exercise their prerogative tients with this disorder. We do not mean to imply that this is the
based on clinical experience and a review of the literature that most sensitive technique for diagnosing this entity, but rather
some readers may disagree with. that the practitioner should not forget to address these regions of
As noted above, the F-wave is a very long conduction path the nervous system in a patient that may be presenting in an
way with a variable response latency from one stimuli to the atypical manner. A second possible disorder in which F-waves
next. This is clearly a physiologic disadvantage in attempting to may be of assistance in alerting the clinician to a particular dis
localize a lesion to a focal region of the nervous system, partic ease is multifocal motor neuropathy with conduction blockY'
ularly In mild disease. This so-called disadvantage, however, Again, it should not be concluded that an absence or reduced
can be used to an advantage in some disorders. In our opinion, number of F-waves is diagnostic of this disease, but rather that
the very fact that the F-wave is traversing the peripheral nerve many practitioners do not routinely study the peripheral nervous
twice can be used to a diagnostic advantage in detecting an early system from the root to the axilla in aU patients presenting with
disease process that is diffusely distributed along the nerve and limb weakness. Conduction studies of the arm and forearm may
may not be detected by assessing a focal neural segment. One be normal, whereas the F-waves may be reduced in number or
such disease entity is diabetic neuropathy.5.164 Although appro absent. This finding should suggest that the region between the
priate reservations have been raised regarding the true sensitiv root and axilla should be studied. No doubt fibrillation poten
ity of F-waves in diagnosing early peripheral nerve disease,232 tials may be detected in distal muscles, but the F-wave can help
there is a sound physiologic basis for considering the use of F direct a more "focal" exam of the relatively proximal neural
waves in attempting to define if there is a generalized mild segments. Having said the above, not all proximal lesions are
particularly amenable to F-wave studies. For example, cervical
and lumbosacral radiculopathies certainly can result in abnor
mal F-wave studies;222.237 however, most of these patients have
more localizing findings on needle electromyography. This is
understandable since the majority of muscles are innervated by
more than one root and most radiculopathies do not produce
complete obliteration of all the nerve fibers in a nerve root. It is
not suprising, therefore, that F-waves are usually abnormal in
radiculopathies only when significant unilevel or multilevel root
disease is present. Although F-waves can be used to study focal
demyelinating lesions,64 it is not our contention that focal en
trapment neuropathies such as carpal tunnel syndrome should
be routinely assessed by F-wave studies. 159 As always, it is in
cumbant upon the practitioners to become familiar with a par
ticular technique and its available literature, and then assess
whether the technique is of value in their patient population.
H-REFLEX
A stimulus applied to the tibial nerve with a magnitude that is
subthreshold for a direct motor response usually produces a late
JIOOO/-LV response when recording from the gastrocnemius-soleus mus
5ms cles in the neighborhood of 30 ms (Fig. 6-12). This potential was
first described by Hoffmann in 1918.95 Magledary and
McDougal performed in-depth electrophysiologic investigations
of this late response by the 1950s and they designated this poten
tial the H-reflex in honor of Hoffmann.145.146 In studying both the
Figure 6-12. H-reflex.An H-reflex evoked from the gastrocnemius H-reflex and the F-wave, Magledary and McDougal defined a
soleus muscle following tibial nerve stimulation. Note that as the cur number of ways to distinguish between these two responses with
rent intensity of the stimulus is slowly increased (lower to upper similar latencies (Table 6-7). A number of clinical applications
trace) the magnitude of the H-reflex increases to a maximum (third have been developed using the H-reflex. Prior to discussing how
trace from bottom) and then decreases with continued elevations in the H-reflex may be employed in the diagnosis of potential
current strength. With a supramaximal stimulus, the H-reflex is re pathology affecting the peripheral and central nervous systems,
placed with an F-wave. it is necessary to discuss the physiology of the H-reflex.
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 245
the threshold level. Additionally, there may be motor neurons facilitatory and inhibitory influences. The progressive decline
that were not previously depolarized that can now fire because of the H-reflex and replacement by an F-wave at sequentially
less EPSP summation is required. The suprasegmental influence greater current intensities is likely a combination of collision,
of central facilitation introduces a potentially significant vari refractory alpha motor neurons, and Renshaw inhibition of the
able when attempting to quantitate the H-reflex amplitude for motor neuron pool (6-12).234.235
diagnostic purposes. Each individual possesses his or her own
level of central nervous system activity with respect to the nec Factors Affecting the H-reflex
essary amount of transmitter directed EPSPs required to poten As previously stated, the magnitude of the H-reflex is subject
tiate alpha motor neuron discharge. to the amount of current delivered to the nerve, ratio of Ia affer
The progressive reduction and eventual disappearance of the ents to motor fibers activated, interpersonal differences in
H-reflex with continued elevation in stimulus strength is poorly suprasegmental facilitatory influences. and level of muscle con
understood, but may be a result of several factors. A mechanism traction. 18) The H-reflex is commonly observed only in the gas
initially proposed relies upon the H-reflex impulses colliding trocnemius-soleus and flexor carpi radialis muscles. The
with the antidromic action potentials propagating in the motor detection of H-reflexes in these two muscles may not be ob
nerves just distal to the alpha motor neurons. 145,239 Remember served in all normal individuals, particularly in the elderly.
that action potentials are generated at the same location in both Contraction of the muscle from which the H-reflex is recorded
sensory and motor fibers, e.g., the popliteal fossa for an H and its agonists may allow an H-reflex to be recorded from
reflex recorded from the gastrocnemius-soleus muscle. If the H where it was previously absent. Again, this is because of facili
reflex impulses are to collide with the antidromic motor action tatory influences decreasing the difference between the alpha
potentials somewhere at the level of the ventral roots or distally, motor neuron's resting membrane and threshold levels. Muscle
sensory action potentials obviously have to conduct signifi contraction is found to not alter the latency of the response sig
cantly faster than the motor impulses in order to traverse and nificantly.2S Contracting the antagonist muscles tends to sup
exit the central nervous system. Recall that about 4 ms is re press the appearance of the H_reflex. 71 ,18.95,153 It is also possible
quired for the EPSP to reach its peak plus an additional 1 ms for through contraction of a muscle to observe H-reflexes where
synaptic transmission. A difference of about 5 ms is the required they are not routinely detected. 172 For example, through muscu
separation between the sensory and motor conduction times. lar contraction, H-reflexes have been detected in the tibialis an
Histologic examination of the peripheral nerves concerned has terior, abductor pollicis brevis, extensor digitorum communis,
revealed similar diameters for both motor and sensory nerves foot intrinsic muscles, and flexor digitorum profundus. 25 ,54,70,174
suggesting that they have similar conduction velocities. IS3 Patients with spasticity resulting from various upper motor
Despite the well-accepted opinion that sensory fibers generally neuron lesions may produce H-reflexes in muscles other than
conduct faster than motor fibers, this has not been found in care the soleus muscIes. 13I ,146,2JS Also, in neWborns, an H-reflex may
ful investigation of afferent and efferent conduction veloci often be seen in the small muscles of the hands and feet. and
ties. 40,41,52,IS3,217 Although it may be possible for fast-conducting usually disappears by 1 year of age.13,94,216
Ia afferents that have activated the lower threshold and rela In addition to contraction of the agonist muscles, it is also
tively smaller slower-conducting alpha motor neurons to collide possible to facilitate the H-reflex with a Jendrassik maneuver
at the ventral root region, this may not be the complete explana by asking the patient to forcefully make a fist. This is signifi
tion for all motor neurons. The fast-conducting antidromic cantly less effective in facilitating an H-reflex than a contraction
motor potentials reach the ventral root at essentially the same of the agonist muscles. 153 Significant potentiation of the H
time the afferent impulses arrive at the dorsal root. Additionally, reflex can occur with post-tetanic stimulation. 135 It is possible to
by strongly contracting the muscle, an H-reflex reappears de generate an H-reflex with a subthreshold response after a
spite a strong stimulus, thereby proving collision is not a major tetanus of 100-500 Hz for 20 seconds lasting about 10-40 sec
component of H-reflex suppression. Therefore another explana onds. The mechanism is unclear but is believed to involve
tion of this phenomenon is necessary. presynaptic facilitation,83
Let us assume that a suprathreshold stimulus is delivered to H-reflex amplitude may be affected by factors other than an
the tibial nerve in the popliteal fossa, thus activating the large Ia tagonist muscle contraction. 172 Forceful active or passive ankle
afferents as well as the large motor fibers conducting at similar flexion and contraction also can markedly reduce the tibial
velocities, In this case, the alpha motor neurons are activated by nerve's H-reflex magnitude. 53,J53 Mild passive stretching of the
the antidromic impulse as discussed previously for the F gastrocnemius-soleus muscle can either facilitate or inhibit the
wave. 112 Additionally, the recurrent collaterals mediate Renshaw H-reflex. 214,236 Vibration is an effective way to suppress the H
cell inhibition of the alpha motor neuron pool. By the time the reflex. 9,20,35,231 Applying a vibrating stimulus to the Achilles
EPSP and synaptic transmission of H-reflex impulses have con tendon in the limb under investigation results in depression of
verged on the alpha motor neuron, it is most likely no longer ca the H-reflex that may outlast the duration of the vibration by
pable of depolarizing the previously activated anterior horn several hundred milliseconds. 20s The mechanism of H-reflex
cells at lower stimulus levels because they are either in a refrac suppression is unknown but may involve presynaptic inhibition
tory state from F-wave generation or under the influence of through primary spindle afferent firing or neurotransmitter de
Renshaw inhibition. It is possible to detect an H-reflex follow pletion. 39,2l4 It is also possible to suppress the H-reflex with
ing inhibition through a supramaximal stimulus if the patient stimuli delivered at several HZ.25
contracts the agonist muscles. This finding strongly argues
against collision as a reason for obliteration of the H-reflex. Diagnostic H-Reflex Techniques
Muscle contraction should not affect whether antidromic im There are two major clinical applications of the H-reflex.
pulses collide with the orthodromic H-reflex, It appears that First, the H-reflex may be used to evaluate the status of the pe
the major component of H-reflex suppression with supramaxi ripheral nervous system with respect to proximal peripheral
mal stimulus delivery is based on the balance between central nerve conduction and potential entrapment of nerve roots, e.g.,
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 247
radiculopathies. Secondly, it is possible to examine the intricate Some investigators prefer to use a needle cathode, requiring less
interactions of segmental and suprasegmental facilitatory and stimulus. In this instance, a large electrode is secured to the patella
inhibitory influences on the two-neuron reflex arc designated to serve as the anode. Using a similar pulse width to that noted
the H-reflex. The H-reflex, therefore, can help us assess both above should not damage the nerve as a subthreshold stimulus is
the peripheral and central nervous systems in both health and used. It is our experience that should surface stimulation fail to
disease. elicit an H-reflex, needle excitation often results in a demonstrable
response. Further study, however, is required comparing the opti
Peripheral Nervous System Applications mal stimulus parameters for needle and surface stimulation.
Perhaps the most common use of the H-reflex is to assess the As stated above, the stimulus is slowly increased until a re
conduction properties of the S1 nerve root in the neural foramen sponse with a latency approximating 30 ms is detected. The cur
region to investigate the possibility of nerve root compromise. rent level is increased in small increments until a motor
A number of studies have confirmed that the primary nerve root response is just noted. One should then optimize the H-reflex by
level mediating the H-reflex is S 1 and although L5 may con decreasing or minimally increasing the current intensity until
tribute to the neural supply of the gastrocnemius-soleus muscles, it the H-reflex magnitude is maximized. Several responses are ob
does not significantly participate in the H_reflex. I.2.3.I84.191.192.200.226.227 served at this stimulus level to ensure a reproducible and stable
The H-reflex from the lower limb is also used to assess the con response. The latency is then recorded to the initial departure of
duction of proximal afferent nerves not accessible to routine the H-reflex from the baseline. This is typically although not
evaluation. Specifically. the H-reflex may demonstrate compro always a positive deflection, most likely because the electrode
mise of the proximal afferent pathways in various polyneu is preferentially detecting the response from the soleus muscle
ropathies and allow one to calculate conduction velocities in and not over its motor point. A characteristic appearance of the
these regions.80·86.224.225.238 One also may examine the H-reflex to H-reflex is a triphasic initially positive potential (Fig. 6-12). It
the flexor carpi radialis (FCR) muscle for upper limb peripheral is not unusual, however, to observe an initially negative H
nerve lesions. It is recommended to adopt a standardized reflex, In either case, the initial baseline departure denotes the
method of applying electrodes in order to minimize potential correct latency measurement. An H-reflex demonstrates a very
errors introduced by variability of anatomic landmarks. stable onset latency from one response to the next. This is quite
different than the rather variable F-wave latency with each con
H-Ref/ex: Gastrocnemius-Soleus Muscle secutive stimulus. Continued elevation of the current strength
Recording Electrodes. Surface recording electrodes are characteristically results in the disappearance of the H-reflex
preferred for this technique as they were used for the develop and the appearance of an F-wave (Fig. 6-12). The H-reflex
ment of the accompanying reference data. Because amplitudes should not be recorded if it is smaller than the M-response or
are not used, needle recordings to document H-reflex latencies demonstrates a variable latency and morphology.
are acceptable provided the same technique is used for both left
and right measurements.
The patient is positioned comfortably in the prone position so 40.14 eo
with the feet off the edge of the plinth. It is often helpful to 49
48
39
7S
place a pillow beneath the legs to cause slight knee flexion. 47 38
41 34
the leg and drawing a line across the popliteal fossa. 19,20 A line 40
33
35
30
40
32
E-l. 3' 27
29
30
with the anode distal. A pulse duration of between 0.5 ms and 1.0
ms is recommended. The current intensity is slowly increased 28
27 24
until the stimulus just activates the large Ia afferent fibers without 26
concomitant activation of the motor fibers or is just threshold for 215 22.64 20
only a few motor fibers. The stimuli should be delivered at a rate LEG LENGTH· LATENCY AGE
of 1 stimulation every 2-3 seconds to avoid suppressing the H (em) (msec) (yrs)
reflex through central mechanisms. It is often necessary to move
the stimulating electrodes either slightly medially or laterally to Figure 6-13. H-reftex nomogram.A nomogram for predicting the
optimize the cathode directly over the tibial nerve. Care should be H-reflex provided the patient's age and leg length (see text for proper
taken to avoid proceeding too far laterally as the peroneal nerve measurement) are known. (From Braddom RL, Johnson EW:
may be excited. This is relatively easy to define as the foot no Standardization of H reflex and diagnostic use in S I radiculopathy.Arch
longer plantartlexes but dorsiflexes with each stimulus. Phys Med Rehabil 1974;55: 161-166, with permission.)
248 - PART II BASIC AND ADVANCED TECHNIQUES
Instrumentation Parameters. A sweep speed of 10 ms/div right responses) smaller than 0.4 108 or 0.5 89 is considered an ab
is optimal for lower limb H-reflex examinations. Although a normal finding and suggestive of possible pathology affecting
sweep speed of 5 ms/div can be used, it is possible for this re the fibers conveying the response. Another study found an am
sponse to be greater than 50 ms in a particularly tall individual plitude ratio (right sidelleft side) of greater than 1.8 (unaffected
or in a person with a peripheral neuropathy. An amplifier sensi side/affected side) to indicate an abnormality.163 In our opinion,
tivity of 200 !J.VIdiv to 500 !J.V/div usually suffices for most re a shortcoming of these studies is a failure to fully explore. the
sponses. Filter settings commensurate with routine motor effect of central facilitation on the "normal" side-to-side ampli
studies are recommended. tude range. Specifically, in persons with a considerable side-to
Reference Values. The technique of Braddom and Johnson side difference no apparent attempt was made to facilitate the
is suggested as it represents a standardized method for obtain response and see if the side-to-side difference would diminish.
ing H-reflex latencies. 19 ,20 H-reflexes are found to correlate This is critical since patients with back pain and no radicular
highly with both age and leg length. A regression equation may axonal/demyelinating lesion may splint the painful side and in
be used to predict the optimal H-reflex latency: H-reflex (ms) = advertantly contract the affected side's foot dorsiflexors ever so
9.14 + 0.46(leg length-cm) + 0.1 (age-yrs). A nomogram based slightly, resulting in diminished H-relfex amplitude.69.156 As
upon this equation also may be used in the clinical setting as a noted above, the effect of antagonist muscles on the H-reflex is
quick reference (Fig. 6-13). When using the nomogram, a line well documented, Therefore, side-to-side amplitude differences
connecting the patient's age and leg length is constructed and for the H-reflex may be of diagnostic use, but the presently
where it crosses the middle set of values predicts the H-reflex available studies are unconvincing regarding the most appropri
latency. A mean H-reflex latency of 29.8 ± 2.74 ms is found for ate amplitude values to use clinically. Obviously, any side-to
a normal population. In this study a side-to-side difference of side amplitude comparisons are of questionable validity in
1.5 ms is predictive of an SI radiculopathy. Some investigators bilateral disease.
use as little as a 1.0 ms difference. In persons aged 60-88 years, When using left/right criteria as sensitive as 1.1 mS,89.l63 it is
an H-reflex can be obtained in up to 92% of persons with a side advisable to always use standardized distances to assist in re
to-side latency difference of 1.8 msY The normal side-to-side producibility. Using anatomic landmarks may result in undue
amplitude differences in persons between 21 and 67 years can latency differences and predispose one to false-positive or false
reach 60% (see Additional Comments for further discussion). 108 negative results.
Additional Comments. Should one have difficulty eliciting Just as for F-waves, it is possible to calculate the H-reflex con
an H-reflex, slight voluntary contraction of the muscle exam duction velocity for the proximal tibial nerve segment. A maxi
ined may facilitate its detection. Although this should not sig mal H-reflex is obtained using the above noted technique. One
nificantly affect the latency, it may be advisable to also use then elicits a maximal M-response for supramaximal excitation
slight voluntary contraction on the contralateral side, particu of the tibial nerve from the same site of stimulation used for the
larly if the left/right differences approach significance. H-reflex, i.e., the anode is rotated proximally. A time of 1 ms is
Caution should be exercised in attempting to use the H-reflex subtracted to account for central synaptic delay. The distance
amplitude for diagnostic purposes as it is highly variable and measured is from the popliteal fossa stimulation site to the TIl
subject to central nervous system influences. The amplitude is spinous process. The formula used to calculate this proximal con
also quite sensitive to electrode placement and may noticeably duction over afferent sensory and efferent motor fibers is: H
change within just a few centimeters, 147,148 If side-to-side ampli reflex CV (mls) =(distance popliteal fossa to Til x 2)/(H-reflex
tudes are to be compared, it is very important to exactly repro latency - M latency 1 ms). This technique can document slow
duce the electrodes' locations since different electrode positions ing of proximal conduction velocities in various peripheral neu
can result in considerable amplitude variations,27 As noted ropathies, such as diabetic polyneuropathy225,226 and uremic
above, several investigations have attempted to define the neuropathy.86 Of course, the same precautions regarding distance
degree of side-to-side amplitude variation in reference popula measurements noted for the F-wave also apply for the H-reflex.
tions, When comparing the smaller of the two responses to the
larger, an amplitude ratio (smallest!largest between left and H-Reflex: SI Central Loop
The traditionally performed H-reflex to the lower limb uses a
PSIS very long pathway reducing its ability to localize a lesion strictly
Stimulation to the Sl nerve root. As result, an attempt has been made to
reduce the pathway over which an H-reflex can be obtained in
the hopes of localizing a lesion to the S 1 nerve roo1. 175 This tech
nique is promising, but requires larger studies to fully assess the
sensitivity and specificity of the S 1 central loop latency.
Recording Electrodes. The recording and ground elec
trodes are positioned in the same manner as for the H-reflex ob
__.~t~j_____~~______ tained through tibial nerve stimulation (see above).
Stimulation. A monopolar needle electrode serves as the
cathode and is inserted 1 em medial to the posterior superior
iliac spine perpendicular to the patient's frontal plane, and a sur
Figure 6-14. Central 51 loop latency. The two peaks of the direct face anode is affixed to the anterior superior iliac spine. The
motor (M) response and the H-reflex (H) following S I nerve root stim cathode is gently inserted until it contacts the sacrum and is then
ulation are shown. The difference between the M and H peak latencies withdrawn slightly. A stimulus pulse duration of 1 ms is used
should be less than 8.0 ms. (From Pease WS, Kozakiewicz R, Johnson with a maximal pulse delivery of 0.5 Hz. The current is slowly
EW: Central loop of the H reflex: Normal value and use in S I radicu increased until a combined direct motor (M) and indirect H
lopathy,AmJ Phys Med RehabilI997;76:182-184,with permission). reflex (H) is obtained,
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 249
Instrument Parameters. The instrument's sweep speed is Reference Values. Onset H-reflex latencies to the rectus
set to 5 ms/div with high- and low-frequency filter settings of 10 femoris, vastus medialis, and vastus lateralis muscles are de
kHz and 20 Hz. A gain of 0.5 to l.0 mV/div is used to best visu scribed as 17.7 ± 1.8 ms, 18.4 ± 1.8 ms and 18.1 ± 1.7 ms, re
alize the response. spectively.too It is important to note that this response may not
Reference Values. An H to M latency difference of 7 ± 0.3 be obtainable even in normal individuals. Slight voluntary con
ms is anticipated in healthy individuals (Fig. 6-14). A latency of traction of the quadriceps and a lendrasik maneuver may assist
8.0 ms or greater is considered indicative of a lesion affecting in the facilitation of the response.
the proximal S 1 conducting pathway.
Central Nervous System Applications
H-Reflex: Flexor Carpi Radialis Because a portion of the H-reflex involves the central ner
Recording Electrodes. It is possible to record an H-reflex vous system, it is subject to both segmental and suprasegmen
from the FCR in most normal individuals. This muscle is inner tal influences. 6,58.71.135 This is best demonstrated by facilitation
vated by C6 and C7 nerve roots and thus the H-reflex may be of of an H-reflex with contraction of the muscle under investiga
assistance in assessing the neurophysiologic status of these two tion and inhibition with antagonist muscle contraction. It
nerve roots and possibly conduction through the brachial should be possible, therefore, to indirectly investigate various
plexus. 38,167,196.197 aspects of the central nervous system with reflex responses by
£-1. A surface E-l electrode is positioned over the belly of studying the H-reflex in both health and disease. 149,158 One
the FCR. This site is located one-third the distance from the common method of using the H-reflex for this purpose involves
medial epicondyle to the radial styloid. I06 a technique of conditioning and test stimuli similar to refrac
£-2. An E-2 is positioned over the brachioradialis muscle. tory period experiments.
Ground. The ground should be secured to the skin just prox The central motor neuron pool excitability can be investi
imal to E-I. gated by using a dual stimulation technique to document the H
Stimulation. The subject may be either supine or sitting reflex excitability or recovery curve. The recording electrodes
with the elbow slightly flexed. The cathode is located over the are positioned as noted above for peripheral nerve techniques. A
median nerve at the antecubital fossa with the anode distal. A stimulator is secured to the tibial nerve at the popliteal fossa.
pulse width of 0.5-1.0 ms is optimal and the current intensity is which has the capability of delivering square wave stimuli 1.0
slowly increased until the H-reflex is maximized with an absent ms in duration with a variable interval between successive im
or minimally present FCR CMAP. The presence of an H-reflex pulses. The initial or conditioning stimulus is delivered at or just
should be verified by increasing the stimulus intensity and ob below threshold for eliciting an H-reflex. This impulse gener
serving for a disappearance of the response and replacement by ates a number of Ia afferent action potentials that enter the cen
an F-wave. The stimuli delivery should not exceed 0.5 Hz. tral nervous system over the reflex arc to condition the alpha
Slight contraction of the FCR may be necessary to detect an H motor neuron pool without causing a motor impulse. A second
reflex in some individuals. or test stimulus is then given through the same stimulating elec
Instrumentation Parameters. A sweep speed of 5 ms/div trodes at a level sufficient to evoke a minimal direct M-re
with a sensitivity of 0.5-1.0 mVldiv and routine motor conduc sponse. Of course, this neural activation also should yield
tion filters should produce clearly recognizable H-reflexes. enough current to activate a large number of Ia afferents with
Reference Values. One may anticipate a latency to the ini the capability of generating an H-reflex independent of the con
tial baseline deflection of 15.9 ± 1.5 ms.Hl6 A side-ta-side differ ditioning impulse. The amplitude of the H-reflex produced by
ence of 0.4 ± 0.3 ms is expected. the test stimulus at increasing time intervals from the condition
ing stimulus is then plotted for each sequential time interval and
H-Reflex: QuadriCeps Muscle describes a characteristic shape reflecting central nervous
Recording Electrodes. Recording the H-reflex from the system segmental and suprasegmental interactions.
quadriceps muscle is somewhat more challenging than either Within a few milliseconds of the conditioning response, the
the gastrocnemius-soleus or FCR muscles. The femoral nerve is H-reflex magnitude is maximal (Fig. 6-15).209 Increasing the
a rather deep structure and difficult to activate with surface time interval between conditioning and test stimulus results in a
stimulation. Because of this, the current intensity is hard to in progressive amplitude decline of the H-reflex to a minimum
crementally deliver and there is little gradation between an value at approximately 75 ms. At interstimulus intervals between
absent and present direct motor response. The utility of a 100 and 200 ms the amplitude of the H-reflex again increases,
quadriceps H-reflex may be of assistance in the L31L4 nerve peaking at about 150-200 ms. As the time interval between the
root compromise.3,162 conditioning and test stimulus continues to increase, the H-reflex
£-1. An E-I electrode may be located over the main muscle amplitude demonstrates a second decline, reaching a minimum
bulk of the vastus medialis, vastus lateralis, or rectus femoris. value at 200-400 ms. The H-reflex amplitude reveals a slow and
£-2. The patella is a convenient site for E-2. progressive increase as the interstimulus time delay approaches
Ground. This electrode should be situated just proximal to 1000 ms. This H-reflex recovery curve is a graphic representa
E-l. tion of the various central nervous system interactions all con
Stimulation. The femoral nerve is excited in the inguinal verging upon the alpha motor neuron pool and reflects the CNS's
region just distal to the inguinal ligament about the region of the normal physiologic state. Although the exact mechanism gener
femoral artery. Cathodal placement is distal to the anode. A ating the above noted curve is unknown, an assumption based
pulse duration of 0.5-1.0 ms is delivered at less than 0.5 Hz upon what little is known about the peripheral/central nervous
with an intensity capable of producing an H-reflex with little, if system provides some insight into the various interactions result
any, M-response. ing in the detected H-reflex recovery curve.
Instrumentation Parameters. The same instrumentation The initial H-reflex response is believed to result from the
setup previously described for the FCR muscle can be used. conditioning stimulus' EPSPs generated by the Ia afferent input.
250 - PART II BASIC AND ADVANCED TECHNIQUES
Tendon Reflex
It is possible to record the electrical activity associated with
the reflex contraction of a muscle induced by acutely stretching
msec a tendon through percussion. A modified reflex hammer is re
quired with the ability to initiate the instrument's cathode ray
Figure 6-15. Postulated pathways mediating the H-reflex's tube sweep. Surface or needle electrodes can then record the
magnitude as elicited with conditioning stimuli. A, Solid line signifies reflex contraction of the muscle following the mechanical
that 2 of 4 la afferent fibers were excited that in turn monosynaptically energy delivered to the muscle's tendon. In brief, the tendon tap
synapse with a motor neuron (MN) but were subthreshold for evok stretches its muscle, which in turn activates the muscle spindle.
ing a response. This same la volley simultaneously proceeded rostral The muscle spindle is a specialized structure consisting of a
ward up the dorsal column tracts (DSCT) to the various structures connective tissue capsule surrounding several types of muscle
depicted in the circle. The vestibulospinal tract (VST) then conveys fibers referred to as intrafusal muscle fibers.I1·19B The intrafusal
these volleys to activate the motor neuron, forming the long-loop muscle fibers are approximately 15-30!Jm in diameter and 4-7
reflex. B. The continuous line reveals the time course of the condition mm long as opposed to the commonly thought-of muscle tissue,
ing of the observed H-reflex by the subthreshold H-reflex stimulus. It extrafusal muscle fibers, which are 50-100!Jm in diameter and
is suggested that the H-reflex amplitude curve is a composite of three several millimeters to many centimeters in length. Sensory in
conditioning factors. i.e., (I) local EPSP (see text) on motoneuron, (2) nervation to the intrafusal muscle fibers is provided by one
long-loop facilitation as shown above. and (3) depletion of transmitter larger myelinated Ia nerve that wraps around the center of the
in the synapses activated by the conditioning stimulus. (From muscle fibers several times and is called the annulospiral
Taborikova H, Sax DS: Conditioning of H-reflexes by a preceding sub ending or primary sensory ending. Stretching of the extrafusal
threshold H-reflex stimuls. Brain 1969;92:203-212, with permission.) muscle leads to a concomitant lengthening of the intrafusal
fibers, which in turn activates the annulospiral ending sending
Specifically, the effects of the conditioning stimulus cause the impulses toward the central nervous system along the Ia affer
Ia afferent-induced EPSPs to occur that have a rise time of sev ents. The Ia afferents cause EPSPs to be produced in the
eral milliseconds. The duration of the rise time produces a facil homonymous alpha motor neurons, resulting in a contraction of
itatory effect that is still present when the test stimulus' Ia the muscle stretched. The intensity of muscle contraction de
afferents arrive. They find the alpha motor neuron pool already pends upon the number and degree to which the annulospiral
in a slightly depolarized state, thereby facilitating an H-reflex endings have been activated. The above description is the clas
from the test stimulus. It is important to realize, however, that sic reflex arc familiar to all. Intrafusal muscle fibers also are in
the subthreshold conditioning stimulus has been depleting a Ia nervated by a second class of sensory fibers, group II fibers,
afferent subpopulation of neurotransmitter substance. Experi which form secondary muscle spindle endings or flower spray
mental results have demonstrated that the subthreshold stimulus endings. Because they do not directly participate in the reflex
activates about 50% of the Ia afferents, hence accounting for the arc the details of their function are not discussed. The intrafusal
50% reduction in the H-reflex by 75 ms. 209 Once the stimulus muscle fibers also possess a motor innervation by small anterior
interval has increased beyond the facilitatory effect of the Ia af horn cells referred to as gamma motor neurons. Unlike the
ferents, the full effect of the transmitter depletion becomes de alpha motor neurons with peripheral nerve fibers in the range of
tectable, reaching a maximum at about 75 ms. Despite the 12-21 !Jm, the gamma efferent diameters approximate 2-8 11m.
above-noted depletion of neurotransmitter, a second elevation in Activation of the gamma fibers also can cause the annulospiral
the H-reflex is noted peaking at about 200 ms. A long-loop fa ending to contract, thus potentiating a contraction of the eXtra
cilitatory pathway traversing up to and back down the brainstem fusal muscle fibers. The gamma fibers, therefore. exert a power
has been proposed to account for this increase in H-reflex mag ful influence on the output of the muscle spindle, which
nitude.(Fig. 6-15) Some portion of the Ia afferent input to the modulates the type of contraction resulting from a tendon tap.
central nervous system not only directly synapses with the The electrical activity associated with muscle contraction
motor neuron pool, but also ascends through the dorsal spinal arising from a tendon tap can be recorded and displays various
cerebellar tract to involve the cerebellum and reticular sub latencies depending upon the length of the afferent and efferent
stance. From these structures descending fibers may be con pathway. The impulse traverses the Ia afferents and alpha motor
veyed through the vestibulospinal tract to also facilitate firing of neurons noted above. The H-reflex has been considered the
the motor neuron pool. It is proposed that the long loop reflex electrical equivalent of the tendon reflex. An important distinc
time course coincides with and accounts for the second eleva tion between the H-reflex and the muscular contraction of a ten
tion in the H-reflex magnitude because it provides EPSPs that don tap is that the H-reflex directly activates the large Ia afferents
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 251
Tibial. Nerve
1-
~
""'t " .A
v
Figure 6-16. Axon reflex. A. Series of axon reflex re
sponses designated I. 2, and 3 demonstrating a constant la !"""" ,,,.,
tency. Note that the axon reflex can either proceed or follow
I
the F-wave. B, Diagrammatic explanation of the axon reflex '1Tt1
I ...J.
(see text). (From Kimura J: Electrodiagnosis in Diseases of
~'
Nerve and Muscle: Principles and Practice. Philadelphia, F.A.
Davis, 1989, with permission.) ..... ;[" //.
\'':
W1"ISI
'Slim
8(2) ....
{
I
j}L...J t tL_ J t ~ mv X
A M 1 2 F 3 10 ms B R ..... ohoc' stlong ShOc::k
in the nerve and bypasses the intrafusal muscle fibers. This is referred to as an axon reflex or A-wave. 68 This intermediate
view, however, may be an oversimplification. The above-noted potential is usually elicited with a submaximal stimulus and dis
"classic" description of the interaction between the Ia afferents plays a constant latency, unlike the varying F-wave. The pre
and alpha/gamma motor system may be less well understood sumed physiology of the axon reflex involves some type of
than previously thought. Human studies reveal that the fusimo neural damage with a collateral sprout from a proximal aspect
tor drive of the gamma system is not necessary to elicit a tendon of the nerve to the muscle. A submaximal stimulus distal to the
reflex. The ease with which a tendon reflex can be obtained may collateral's branch point activates a significant portion of the
be more related to the "central excitability" state of the alpha nerve but spares some fibers. The orthodromic impulses results
motor neurons than the gamma system's influence on the in a less than maximal CMAP while the antidromic impulse
muscle spindle.21.22.24 The muscle's response to a constant proceeds proximally to encounter the branch point. A portion of
tendon tap varies, suggesting that the central nervous system's the electrical impulse proceeds distally along the collateral
segmental and suprasegmental influences are important and while the remainder of the impulse continues into the CNS. The
necessary factors affecting the reflex response. The H-reflex action potentials in the collateral sprout then activate a small
demonstrates the same independence of the fusimotor system portion of the muscle resulting in the axon reflex response. The
that the tendon reflex does. Additionally, the afferent volley in major antidromic impulse backfires in the motor neuron pool to
duced by electrical stimulation for the H-reflex is a synchro then yield the F-wave. Increasing the stimulus intensity elimi
nized volley, whereas the tendon tap afferent volley is nates the axon reflex because the entire nerve is now depolarized,
considerably more dispersed in time. EPSP rise times from including the aberrant collateral branch, thus resulting in a syn
tendon percussion are 8.3 ± 2.5 ms, whereas those from the H chronous activation of the entire nerve. The antidromic impulses
reflex are 3.5-5.5 ms. The combination of dispersed action po are induced in both the collateral branch and the main nerve to
tential volleys and longer rise times for the tendon tap reflex collide proximally, thus eliminating the delayed axon reflex
suggest that it may not travel the same central pathways to action potential. Rarely, one may note that the axon reflex per
achieve the muscle contraction observed with the H-reflex. sists despite a supramaximal stimulus. In this instance the
There is sufficient time in tendon tap reflex activity, temporal mechanism for the axon reflex is obscure but may occur be
dispersion of action potential volleys combined with relatively cause the branch generating the axon reflex is somehow isolated
long EPSPs, to traverse disynaptic and trisynaptic pathways from the impulse either through connective tissue, electrical
centrally. This also applies to a lesser degree to the H-reflex. "shielding" from muscle or bone, or some other poorly under
These findings suggest that the classic acceptance of a monosy stood reason. l25
naptic reflex arc for all fibers activated by either a tendon tap or It is also possible to localize the site of the collateral sprout
H-reflex traveling a single synapse may be inaccurate.21.22.24.231 producing the axon reflex by slowly moving the site of neural
A more plausible explanation suggests that the motor neurons depolarization to sequentially more proximal locations. As the
of lowest threshold may be activated by a monosynaptic arc site of neural activation moves more proximally, the latency of
through the fastest Ia afferents, whereas motor neurons of the CMAP increases, whereas the axon reflex latency decreases
higher threshold fire through several synapses initiated by the because the branch point is closer to the cathode. When the axon
fastest Ia afferents and single synapses of relatively slower Ia reflex disappears, the stimulus is now just proximal to the branch
afferents. This central combination of synapses and rate of af point. Should the branch point depart the damaged nerve at a site
ferent conduction serve to yield a more synchronous output in more distal than the lesion, localization is not possible. This is
dependent of the fusimotor system. rather obvious as more proximal stimulation does not result in an
absent axon reflex. indicating a more distal branching. In this
Axon Reflex case, one can determine the collateral sprout's conduction veloc
A response may occasionally be observed with a constant la ity.68 Of course, should an immature collateral be present, its
tency between that of the CMAP and the F-wave or exceeding conduction velocity can be considerably slower than that of the
the F-wave. particularly from the small muscle of the hand and main portion of the nerve. In this instance, it is possible for the
rarely from the intrinsic foot muscles (Fig. 6-16). The potential axon reflex to follow instead of precede the F-wave. The presence
252 - PART II BASIC AND ADVANCED TECHNIQUES
of an axon reflex is simply a nonspecific indication that the nerve nerves influencing cutaneous blood vessels and sweat glands,
has most likely experienced some type of chronic insult that re the technique is quite demanding and limited primarily to re
sulted in a collateral sprout. An axon reflex can be seen in multi search facilities. 26,84,23o A simple method of evaluating sympa
ple chronic neuropathies such as radiculopathies. plexopathies, thetic skin activity is the galvanic skin response.l 31.178 Following
peripheral neuropathies, and motor neuron disease. 68 ,193 It is pos an emotional or noxious stimulus the sudomotor activity medi
sible to observe axon reflexes in some normal persons with rou ated by the sympathetic nervous system results in an alteration
tine nerve conduction studies because of possible subclinical in the skin's resistance to an electrical current. It is possible to
nerve injury or some other ill-defined reason. Axon reflexes, use commonly available electrodiagnostic medicine equipment
however, are a common occurrence in normal individuals when to examine a similar response mediated by the sympathetic
examined with single-fiber electromyography. Caution should system, I.e., the sympathetic skin response.
be exercised when a late potential is observed. In addition to the Recording Electrodes. The sympathetic skin response is
possibility of detecting an F-wave, H-reflex, or axon reflex, there relatively easy to perform and should be tried by beginning
are a number of potentials following a stimulus that are none of practitioners,82 Commonly available surface recording elec
the above, Additional "late" potentials can be seen with neural trodes are used. Only a few of the possible nerve techniques are
stimulation because of repetitive firing of the nerve trunk, slowly described but essentially any aspect of an limb may be used.
conducting poorly myelinated nerves, ephaptic conduction of in E-1. For upper limb median nerve studies an E-J recording
jured nerves, intramuscular ephaptic conduction loops (complex electrode is secured to the palmar surface of the hand. 202 In the
repetitive discharge), an axon loop, or other unexplained electri lower limb, an E-I electrode can be positioned to the dorsum of
cal pathways, 188 190,201 the foot for peroneal nerve stimulation and on the foot's plantar
An A-wave can be observed in many different types of lesion aspect for tibial nerve excitation.
including polyneuropathy, radiculopathy, motor neuron disease, E-2. In the upper limb, E-2 is located on the dorsum of the
Guillain-Barre syndrome, plexopathies, myopathies, and focal hand. For peroneal nerve stimulation, the plantar aspect of the
nerve injuries. 12 It is rare, however, to observe an axon reflex re foot is used, whereas the foot's dorsum is appropriate for tibial
sponse in normal individuals with the exception of an occa nerve activation.
sional A-wave detected in the foot intrinsic muscles innervated Ground. This electrode is positioned just proximal to the E
by the tibial nerve. Therefore, documenting an A-wave in any 1 electrode with respect to the cathode's location.
response other than from the tibial nerve is considered indica Stimulation. The stimulator is positioned in the routine
tive of pathology by some authors. 12 manner over the desired median nerve at the wrist and peroneal
and tibial nerves at the ankle. A stimulus is applied to each
Sympathetic Skin Response nerve with a pulse width of 0.1 ms and a current intensity ap
All of the previously described nerve conduction techniques proximating 10-20 mA or enough to elicit a slightly uncomfort
examine either sensory or motor nerve fibers or both. The pe able sensation. 180 Because the response readily habituates, the
ripheral nervous system, however, not only contains sensory stimuli are delivered at irregular intervals over several minutes.
and motor fibers, but autonomic nerves as well. The majority of There should be a pause of several seconds between successive
nerve conduction studies only evaluate the fastest-conducting stimuli. About 10 stimuli are recommended as each response
fibers and do not consider the more slowly conducting myeli can vary somewhat and only responses that are consistent are
nated or unmyelinated fibers, e.g., the sympathetic fibers con selected for analysis.
tained within the peripheral nerves. It is possible to investigate the conduction velocity of the
Initially, the autonomic nervous system could only be investi fibers mediating the sympathetic skin response (Fig. 6-17). A
gated electrophysiologically with the insertion of a fine needle second stimulus site at a more proximal location is selected
recording electrode into the substance of a peripheral autonomic once a satisfactory distal potential is obtained. The same para
nerve and recording the ensuing electrical activity, I.e., mi meters are used for proximal stimulation as described above.
croneurography.26,84,220 Although microneurography is capable Instrumentation Parameters. A sweep speed of 500
of distinguishing between the sympathetic fibers conveying im ms/div is optimal as this response is mediated by slowly con
pulses controlling intramuscular blood supply and sympathetic ducting C fibers and substantial time is required to resolve the
sympathetic skin response. Of paramount importance is the
bandpass selected for this technique. A low-frequency filter of
0.5 Hz or less is necessary as the recorded potential has signifi
cant low frequency components. The high frequency filter
should approximate 2,000 Hz. An amplifier sensitivity of
200-1,000 JlV/div usually suffices for most individuals.
Reference Values. The onset latencies for upper and lower
limb studies are 1.39 ± 0.07 seconds and 1.88 ± 0.11 seconds,
respectively.2OO Conduction velocities in the upper limb approxi
mate 1.57 ± 0.11 mls and for the lower limb are 1.02 ± 0.07 m/s.
Amplitudes are 806 ± 322 JlV and 640 ± 276 JlV in the upper
JIOOO,u.V
and lower extremities, respectively.
IOOOms Additional Comments. Although the actual technique of
eliciting a sympathetic skin response is relatively easy, the
Figure 6-'7, Sympathetic skin response. Sympathetic skin re actual response can be quite variable. 7,37.221 Habituation of the
sponse from the palm of the right hand following right median nerve response also can be a problem. 221 The practitioner should be
stimulation at the wrist (upper trace) and elbow. The conduction ve prepared for considerable amplitude variation from one re
locity of the sympathetic fibers is determined to be 1.3 m/s. sponse to the next. It is important to have the patient relaxed and
Chapter 6 SPECIAL NERVE CONDUCTION TECHNIQUES - 253
respond to as little external stimuli as possible between succes 16. Borg J: Refractory period of single motor nerve fibers in man. J Neurol
Neurosurg Psychiatry 1984;47:344-348.
sive stimuli. Temperature can have a significant effect on the re 17. Borg J: Conduction velocity and refractory period of single motor nerve fibres
sponse and should be monitored throughout the procedure with in motor neuron disease. J Neurol Neurosurg Psychiatry 1984;47:349-353.
a recommended temperature for upper and lower limb studies 18. Borg J: Conduction velocity and refractory period of single motor nerve
similar to that of routine nerve conduction studies. A correction fibres in antecedent poliomyelitis. J Neurol Neurosurg Psychiatry 1987;
50:443-446.
factor of 0.088 seconds/OC is recommended. 35 Preliminary in 19. Braddom RL, Johnson EW: Standardization of H reflex and diagnostic use in
vestigations in patients with various peripheral neuropathies SI radiculopathy. Arch Phys Med Rebabill974;55:161-166.
suggest that the sympathetic skin response may be of some as 20. Braddom RL. Johnson EW: H reflex: Review and classification with suggested
clinical uses. Arch Phys Med RehabilI974;55:412-417.
sistance in evaluating autonomic fibers in these diseases. 202 21. Burke D, McKeon B. Skuse NF: The irrelevance of fusimotor activity to the
Continued studies with this technique are required to adequately Achilles tendon jerk of relaxed humans. Ann Neurol 1981; 10:547-550.
determine its clinical utility. 22. Burke D, McKeon B. Skuse NF: Dependence of the Achilles tendon reflex on
the excitability of spinal reflex pathways. Ann Neurol 1981; 10:551-556.
23. Burke D, Gandevia SC, McKeon B: The afferent volleys responsible for spinal
proprioceptive reflexes in man. J Physiol 1983;339:535-552.
CONCLUSION 24. Burke D, Gandevia SC, McKeon B: Monosynaptic and oligosynaptic contribu
tions to human ankle jerk and H-reflex. J Neuropbysiol 1984;52:435-448.
25. Burke D, Adams RW. Skuse NF: The effects of voluntary contraction on the H
The specialized nerve conduction techniques discussed in reflex of human limb muscles. Brain 1989;112:417-433.
this chapter are complementary to those described in the previ 26. Burke D: Microneurography. impulse conduction, and paresthesias. Muscle
ous chapter. Although a number of the more specialized meth Nerve 1993;16:1025-1032.
ods of investigating the nervous system may not be used in most 27. Burke JR: Multielectrode recordings of tibial nerve H-reflexes at various triceps
surae muscle sites in the right and left legs. Electromyogr Clin Neurophysiol
patients routinely, it is nevertheless important for the practi 1997;37:277-286.
tioner to be familiar with both the methodology and utility of 28. Cherington M: Accessory nerve: Conduction studies. Arcb Neurol
these techniques in order to know when their use is most effica 1968;18:708-709. .
29. Cherington M: Long tboracic nerve: Conduction studies. Dis Nerv System
cious. These techniques should be practiced until proficiency is 1972;33:49-51.
achieved so that an absent response can be confidently declared 30. Chroni E, Panayiotopoulos CPo F tacheodispersion: Quantitative analysis of
abnormal as opposed to its absence being a result of technical motor fiber conduction velocities in patients with peripheral neuropathies.
difficulty or a lack of skill. The actual utility of the special nerve Muscle Nerve 1993;16:1302-1309.
31. Cragg BG. Thomas PK: Changes in nerve conduction in experimental allergic
conductions is discussed throughout the remainder of this text neuritis. J Neurol Neurosurg Psychiatry 1964;27:106-115.
with respect to specific disorders. 32. Davis FA: Impairment of repetitive impulse conduction in experimentally de
myelinated and pressure injured nerves. J Neurol Neurosurg Psychiatry
1972;35:537-544.
33. DeLisa lA, Mackenzie K. Baran EM: Manual of Nerve Conduction Velocity
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motor nerve fibres to the small muscles of the hand and fool. J Neurol crofilaments. Int Rev CytoI1972;33:45-75.
Neurosurg Psychiatry 1959;22:l75-181. 242. Yates SK. Brown WF: Characteristics of the F response: A single motor unit
218. Thome J: Central responses to electrical activation of the peripheral nerves sup study. J Neurol Neurosurg Psychiatry 1979;42:161-170.
plying the intrinsic hand muscles. J Neurol Neurosurg Psychiatry 1965;28: 243. Young RR, Shahani BT: Clinical value and limitations of F-wave determina
482-495. tion. Muscle Nerve 1978; I :248-249.
Chapter 7
Needle Electromyography
CHAPTER OUTLINE
Examination
Neural Generators of Abnormal Spontaneous
Muscle at Rest • Insertional Activity • Minimal to Moderate Potentials
Contraction/Recruitment • Information Synthesis Fasciculation Potentials • Myokymic Discharge • Continuous
• Impression Formulation Muscle Fiber Activity • Cramps • Multiple Discharges
• Tremor
Electrical Activity In Muscle
Electrophysiology of Muscle • Action Potential Generation Muscle Generators of Abnormal Voluntary Activity
• Local Circuit Currents· Local Circuit Model of Waveform Neural Loss • Motor Unit • MUAP Findings Following
Morphology Denervation/Reinnervation
Activity
Needle Electromyography: Relevant Issues
Single Muscle Fiber (Triphasic Waveform) • Motor Unit Pain on Needle Examination • Contraindications and
Action Potentials • Anatomy • Physiology • Recruitment Complications Related to Needle Examination • Sterilization of
Principles • Parameters Needle Electrodes • Muscle Biopsy/Serum CPK Level
Inserting a needle electrode into muscle tissue and recording PREPARATION FOR THE NEEDLE
the ensuing electrical activity is referred to as needle elec EXAMINATION
tromyography (EMG). This is one of the fundamental portions
of the electrodiagnostic medicine consultation. Clinical elec THE PATIENT
tromyography can be thought to originate with the introduction
of the concentric needle electrode by Adrian and Bronk in Prior to discussing the actual needle examination, several
1929. 2 Technological advances in electronics and microcomput general precepts must first be recognized. It is important to re
ers have enabled the development of multiple data acquisition member that the needle electromyographic examination can be
methods leading to additional ways of investigating the electri at best somewhat uncomfortable and at worst barely tolerable.
cal activity generated by the muscle fiber. We will explore A relatively pleasant and productive needle examination can be
normal and abnormal muscle electrical activity that can be de experienced by both the patient and physician. provided the
tected with a needle recording electrode placed within muscle physician considers several simple but worthwhile principles. I 12
tissue. One of the most important goals the physician can accomplish
257
258 - PART II BASIC AND ADVANCED TECHNIQUES
is to gain the confidence and cooperation of the patient. In addi monopolar and standard concentric needle electrodes, obviating
tion to a professional demeanor, communication is the single sterilization for most routine needs. It is still acceptable to use
most valuable factor in achieving meaningful data. The physi non-disposable needle electrodes, provided they are soaked in
cian should inform the patient as to the reason for performing standard bleach solution (sodium hypochlorite) for approxi
the needle examination, how the information gained may help mately 15-20 minutes, rinsed clean, and then sterilized. During
establish a diagnosis, and what may be experienced during the needle insertion, it may be of benefit to use distraction tech
examination. Informed patients are usually cooperative because niques such as applying pressure about the needle insertion site
they are participating in their care as opposed to having some with the free hand, talking to the patient about his or her various
thing done to them. interests, or other helpful maneuvers to keep the patient's mind
The patient's anxiety level may be diminished by accurately, off the needle insertions.
but not graphically, explaining that some tolerable discomfort
may at times be felt with needle insertion and movement. THE EQUIPMENT
Attempting to convince the individual that pain will not be expe
rienced is inappropriate and reduces the examiner's credibility The specific electrodiagnostic instrument one uses is usually
when pain is indeed noted. Most patients will tell the physician based more on preference than actual capabilities. Most of the
that they would like to be informed just prior to needle insertion equipment manufacturers offer virtually the same options which
in order to prepare themselves. Giving the patient the option of are adequate to perform a routine needle electromyographic ex
preparation offers some modicum of control which is often ap amination. The added expense of multicolored graphic displays
preciated. Displaying the needle electrode is usually inadvisable and various data manipulation options are often unnecessary and
unless requested because needle length is frequently translated rarely used by most practitioners. Before purchasing an instru
into pain. Many physicians refer to the needle electrode as a ment, the clinician needs to inquire about the following: (1) am
"pin" or similar term to diminish the anxiety associated with the plifier input impedance and common mode rejection ratio, (2)
designation "needle." Gauze or tissue within easy reach com variable filters, (3) analog-to-digital conversion, (4) trigger and
bined with firm pressure over the needle site following needle delay, (5) eathode ray tube (CRT) resolution, and (6) service.
electrode withdrawal is usually quite helpful in controlling pos The instrument's amplifier is one of its most important com
sible blood loss. Bloody tissues and pads should be kept from ponents. The input impedance should be greater than or equal to
patient view and disposed of efficiently to minimize anxiety. It 10 MQ thereby ensuring most of the voltage detected will be
may be difficult to tell the patient how many more muscles will amplified and not lost to the recording electrode. 75 •77.21&
need to be examined when requested to do so, but an approxi Differential amplification quality is also crucial to maximizing
mate number with an explanation for the uncertainty often the signal while eliminating common mode noise. This is usu
allows the patient to prepare adequately. Finally, the patient ally measured by the common mode rejection ratio, which
should be informed that muscle soreness for a day or two occa should exceed 10,000: 1. The practitioner must be familiar with
sionally accompanied by a small degree of bruising around the filters and their ability to help or confound the observed results.
needle site can occur. Mild over-the-counter analgesics typi Optimal filter settings for the routine (qualitative and not quan
call y suffice until the pain spontaneously resol ves. 1l2 titative) needle examination are 10-30 Hz for the low-frequency
(high-pass) filter and 10,000-30,000 Hz for the high-frequency
THE EXAMINER (low-pass) filter.1 5,218 Beware of instruments that have preset
filter settings as they may be inappropriate for the test per
The practitioner performing the needle electromyographic formed and compromise flexibility in altering the recording pa
examination is a medical consultant and should use the history rameters, particularly if there is a desire to reproduce another
and physical examination combined with the needle examina laboratory's conditions, Once the analog signal is amplified and
tion's electrical findings to arrive at an electrodiagnostic medi filtered, most modem instruments convert the analog signal into
cine diagnosis. Upon completion of the history and physical a digital representation (analog-to-digital conversion) so that it
examination, the electrodiagnostic medicine consultant should can be "frozen" on the screen and analyzed in detail. The
have a clear idea regarding which muscles should be examined process of converting an analog signal to a digital one requires
to arrive at a correct diagnosis. Informing the patient of the in an analog-to-digital converter, which effectively takes a real
tended plan is usually helpful in gaining cooperation. It is help time signal and translates it into binary code. During the needle
ful to keep in mind, however, that the electrodiagnostic examination, it is often helpful to position a motor unit action
medicine examination is a dynamic process and may require potential in the same place on the CRT screen each time it fires.
slight alterations in the exact muscles explored as information is This allows one the ability not only to obscrve the potential's
acquired. This is an important concept to convey to the patient morphology, but also look for time locked potentials (satellite
particularly when several more muscles than originally antici potentials)147 that are not part of the main complex. These time
pated require examination. If one is unsure of the reason for ex locked potentials can be misinterpreted as separate potentials on
amining the patient, the referring physician should be contacted a free running CRT screen. The trigger and delay line triggers
to avoid an unnecessary repeat study at a later time. Discussing on a particular portion of the desired potential and delays the
the patient with the referring physician can be quite productive signal while the CRT trace advances a preset amount, resulting
in considering alternative diagnostic strategies and is often ap in the potential repetitively appearing in the same place on the
preciated as a recognition of thoroughness. CRT screen each time it fires (see Chapter 3). The CRT contains
All necessary equipment should be organized for efficient discrete points of resolution to define the waveform; approxi
use. Searching for supplies while the patient is waiting to be ex mately 500 points across the screen suffices for all routine pur
amined can be quite disconcerting for everyone. It is a good poses. One of the most important considerations regarding any
practice to use disposable gloves during the needle examination. piece of equipment is the service provided by the factory. This
Most manufacturers now offer technically acceptable disposable knowledge is usually obtained by talking to colleagues who
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 259
have worked with the company in question. Finally, it is impor necessary depending upon the individual patient. When examin
tant to remember that the skill required to perform a competent ing the muscle at rest, the needle should be inserted along a par
needle examination is in the "hands" of the practitioner and not ticular line and then withdrawn to the subcutaneous position
the instrument, irrespective of its cost. and redirected along another path while still in the same muscle.
Perhaps one of the most discussed aspects regarding the Performing this several times allows one to explore rather large
needle examination is the type of needle electrode used. Most portions of the muscle while using only one skin puncture site.
routine needle examinations will be performed with either a Once the needle is within muscle tissue, pain can also be re
monopolar or concentric needle electrode. 71 ,167,180 Significant duced by avoiding structures such as the endplate region, which
energy is expended at conferences and in publications regarding yields characteristic potentials and sounds (see below), perios
the benefits and detriments of these two needle types. Unfor teum, nerves, vessels, and tendons. ll2
tunately, this issue typically becomes rather emotional and is When voluntary motor units are to be assessed, the patient
based more on what type of electrode the individual trained with must contract the muscle. It is usually best to withdraw the
as opposed to objective documentation of the electrode's merits needle to the subcutaneous position to avoid the muscle bending
or faults. It is the authors' opinion that each electrode has partic the needle or the needle tearing muscle tissue. 112 Isometric
ular characteristics that one may wish to employ for specific in muscle contractions are tolerated rather well and the needle can
dications and that the competent electrodiagnostic medicine be reinserted into muscle tissue from the subcutaneous location
practitioner should be familiar with and use both electrodes. into actively contracting muscle with relatively little muscle
The reader is referred to Chapter 3 for a detailed discussion of injury. The paraspinal muscles may occasionally present a chal
the electrodiagnostic medicine equipment. lenge to the practitioner regarding relaxation. With the patient
in the prone position, placing several pillows under the chest so
that the forehead barely touches the plinth (cervical paraspinal
THE ART OF THE NEEDLE EXAMINATION muscles) or under the abdomen so the lumbosacral region is
rather arched (lumbosacral paraspinal muscles) may help. In
The needle electromyographic examination is predicated both instances, the author has found that having the patient
upon a great deal of neuroscience, but there is also considerable place both arms off the plinth and hang limply facilitates
technical skill "in the hands" of the examiner. i.e., the "art of the paraspinal muscle relaxation. Should this not produce electrical
needle examination." There is more to the needle examination silence with the needle in the cervical paraspinal muscles,
than placing needJes into muscles and mastering the knowledge having the patient gently push the forehead against one of the
regarding anatomy and disease pathophysiology. It takes years examiner's hands may help in that the firing of the neck flexors
to gain the sense of how best to examine a particular muscle, can relax the neck extensors. In the lumbosacral region, the pa
minimize pain upon needle insertion. gain the patient's confi tient can be asked to tighten the stomach muscles against the ex
dence, possess a "feel" for what muscles will be most revealing aminer's hand to accomplish the same effect described for the
for a specific lesion in any given patient, etc. Diligent practice neck. 128 It may also help to place pillows under the patient's
and keeping informed about recent advances in electrodiagnos legs, producing slight knee flexion. The patient can then be told
tic medicine will reward the practitioner with a special ability to to gently press the knees into the plinth in an attempt to relax
assist in the diagnosis and treatment of patients afflicted with the lumbosacral paraspinal muscles. Paraspinal muscle relax
diseases of the central and peripheral nervous systems. Several ation can also be achieved at times with the patient in the side
"hints" gained from experienced electrodiagnostic medicine lying position. Muscles on either side of the spine may be
practitioners can help the relatively less seasoned examiner examined, as relaxation of a particular side is highly individual
enjoy a more productive needle examination. ized. Extensor muscles, especially of the forearm, are also often
An initial place to begin is to implement the general guide difficult to relax. In the authors' experience these motor units
lines discussed above regarding the patient and examiner. A few often stop firing when the forearm is switched from neutral to a
specifics with respect to the needle examination may also be more supinated position, such that the muscles do not act any
beneficial in minimizing patient discomfort and obtaining re longer as antigravity muscle. Additionally, a towel roll may be
vealing information. placed under the patient's wrist with the forearm supinated
It may be worthwhile in a particularly anxious patient to per thereby permitting relaxation of the forearm extensor muscles.
form the examination in a quiet location, dim the room lights, These are just a few of the helpful hints in performing the
speak in a calming tone, and keep the patient comfortable re needle examination that the authors have found useful over the
garding room temperature. Prior to piercing the skin over a se years. Of course, none of the techniques described works all the
lected muscle, it is often possible to find an area that is time in all patients. Discussing solutions to these issues with
relatively less painful than others by gently touching the skin one's colleagues can be rather helpful in trying to solve various
surface with the needle tip in several locations. This is an at problems regarding the art of the needle examination.
tempt to find a region of skin that is less wen innervated and
minimize pain upon piercing the skin. During the actual punc
turing of the skin, pinching or applying firm pressure near the PERFORMING THE NEEDLE ELECTRO·
needle site while simultaneously inserting the needle electrode MYOGRAPHIC EXAMINATION
can reduce discomfort. The author prefers to stretch the region
of skin about to be penetrated with the first and second digits of In this section, the needle electromyographic examination
the hand not holding the needle to facilitate needle insertion, refers to the qualitative needle exploration of muscle most practi
Either before the needle is inserted or while it is in the subcuta tioners think of when using the term electromyography or needle
neous tissue, the limb should be optimally positioned to en EMG. The beginning practitioner may wish to divide the needle
hance complete relaxation. Flexion or extension of the major electromyographic examination into several subcomponents to
joint(s) associated with the muscle under investigation may be assist in mastering the procedure as a whole. One of the most
260 - PART II BASIC AND ADVANCED TECHNIQUES
MUSCLE AT REST
Prior to inserting the needle electrode into the patient's muscle,
the instrument's amplifier settings must be optimized. The ampli
fier's sensitivity is adjusted to 50 IN/div, while the sweep speed
is usually 10 ms/div. 75,128,218 Sensitivities of 100 IlV/div can be
used, but care must be taken as some potentials may be rather
small and, therefore, not detected. A sweep speed of 5 ms/div has
been recommended; however, for most routine needle examina
tion, 10 ms/div is sufficient. Low filter settings of 10-30 Hz and
high filter settings of 10,000-30,000 Hz will avoid distortion of
most potentials likely to be detected. A 6O-Hz notch filter should
be avoided if at all possible to preclude signal distortion. Figure 7-1. Needle insertion. A needle recording electrode is in
The patient is usually placed either supine or prone, depend serted into four separate regions of muscle through one skin insertion
ing upon the muscle to be examined, and completely relaxed. site. Three successive depths (S) are sampled for each along each side
The individual muscle to be investigated is positioned to facili of the pyramid. (From Cohen Hl. Brumlik J: A Manual of Electro
tate relaxation. If a monopolar needle is used, the reference neuromyography. New York. Harper & Row Publishers, 1968, p 40, with
electrode is located relatively close to the site of insertion and a permission.)
ground is placed on the patient in a convenient location. A stan
dard concentric needle only requires a separate ground as the is purposefully directed through the muscle to induce electrical
cannula serves as the reference electrode. The needle should be activity that is not present spontaneously. During this portion of
quickly inserted through the skin to minimize patient discom the investigation, the instrument's settings remain unchanged
fort. As noted above, it may be helpful to spread the skin overly and the needle is sequentially inserted through the muscle in
ing the insertion site with the hand not holding the needle to 0.5-2 mm increments with a several second pause between each
make the skin taut. Loose skin tends to be dragged by the needle insertion. The exact number of serial insertions along one direc
and this impedes a quick and relatively painless insertion. As tion depends upon the muscle's thickness. Once the needle elec
the needle passes through the subcutaneous tissue, little electri trode has been positioned sufficiently deep in the muscle
cal activity is noted. A slight amount of resistance may be felt (several centimeters for limb and paraspinal muscles and sev
when the connective tissue surrounding the muscle is encoun eral millimeters for facial and sphincter muscles), the electrode
tered. A gentle thrust of the needle easily pierces this barrier and is withdrawn to the subcutaneous tissue and redirected along a
a burst of electrical activity (Insertional activity: see below) is different axis, This procedure is replicated mUltiple times until
typically seen signifying that the needle is now in muscle tissue. a somewhat pyramidal region of muscle has been examined
Healthy muscle is electrically silent at rest, provided the needle (Fig. 7-1). Note that only one skin insertion site is necessary to
electrode is not in the endplate region (see below), During this explore a relatively extensive portion of the muscle. Upon com
portion of the needle examination, the practitioner attempts to pleting this portion of the investigation, it is good practice to ex
observe spontaneous activity, i.e., electrical activity not under amine other regions of the same muscle through one or two
voluntary control or induced by the examiner. It is often helpful separate needle insertion sites, particularly if pathology is sus
during this portion of the examination if the beginning practi pected. Alternatively, the examiner performs still more redirec
tioner releases the needle electrode to avoid subtle movements tions using the same insertion. In this respect it should be noted
that may inadvertently induce electrical activity. One can then that the viewing field of the needle electrode is very limited.
be certain that any observed electrical activity is either sponta Healthy muscle tissue will produce bursts of electrical poten
neous or under voluntary control (lack of relaxation) and not ar tials (insertional activity) with each needle insertion that persists
tifactually induced by the examiner. Both normal and abnormal for only a short time following cessation of needle move
muscle activity at rest will be discussed separately. ment.232-234 The electrical potentials detected are believed to
result from the needle electrode mechanically depolarizing the
INSERTIONAL ACTIVITY muscle fibers it contacts while moving through the muscle.
These insertional potentials are also referred to as "injury poten
The second step of the needle electromyographic examination tials."232,233 The electrical activity associated with needle move
is referred to as insertional activity because the needle electrode ment may fall in the normal range (normal insertional activity),
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 261
persist following needle movement (increased insertional activ medicine consultation), data acquisition may alter the initial
ity), or barely be detected and possibly approach electrical si plan of study. It is important for the practitioner to recognize
lence (decreased insertional activity). These three possibilities that the electrodiagnostic medicine examination is dynamic and
and their clinical significance will be explored separately. can flow in a number of directions as the investigation unfolds.
One may need to modify the order of the examination, number
MINIMAL TO MODERATE CONTRACTIONI of muscles studied, or number of limbs assessed at any point
RECRUITMENT during the consultation. It is impossible, therefore, for someone
other than the practitioner to simply perform "routine" tests and
Following the muscle at rest and insertional activity assess present them for analysis at a later time. The electrodiagnostic
ment, it is then necessary to evaluate the electrical potentials medicine examination is very different from reading an electro
generated by the voluntary activation of motor units. 211 The cardiogram in isolation from the patient.
patient is instructed to gently activate the muscle by just During the course of the electrodiagnostic medicine consulta
"thinking" of a small contraction. The electrical potentials tion, needle electromyographic findings may begin to suggest a
produced by all of the single muscle fibers innervated by one particular diagnosis. The practitioner must be thoroughly famil
nerve summate to form motor unit action potentials (MUAPs) iar with both neuromusculoskeletal anatomy and pathophysiol
with characteristics that can be assessed such as morphology ogy to consider multiple avenues of exploration. Abnormalities
and recruitment.33.131 A few MUAPs regularly firing on the found in a group of muscles must be characterized as belonging
CRT screen is the desired result. The MUAPs should not vary to a particular distribution suggestive of pathology affecting a
in their amplitude from one firing to the next. The instrument root, peripheral nerve, or a more generalized process for exam
sensitivity may need to be reduced to 500 J1VIdiv or less to vi ple. The examination is complete when the acquired data can
sualize the entire potential on the screen. In the performance explain not only the patient's symptoms, but also any other ab
of routine qualitative needle electromyography, one is primar normalities uncovered during the electrodiagnostic medicine
ily looking for gross abnormalities of MUAPs such as: ampli examination. The electrical data obtained from the needle elec
tudes approaching 5 mV or more, MUAPs with more than tromyography (and nerve conduction studies) combined with
four phases (polyphasic MUAPs), MUAP durations abnor the history and physical examination is synthesized, based upon
mally long or short, and recruitment disturbances. If the the physician's expertise, to formulate an electrodiagnostic
above abnormalities are suspected, then quantitative needle medicine impression.
electromyography is recommended to accurately assess and
quantify the MUAPs' parameters. IMPRESSION FORMULATION
The motor units activated at low levels of contraction are type
I and produce the MUAPs routinely analyzed.35.183 With increas Once the data has been gathered and analyzed in the context
ing force of contraction, the initially present MUAPs increase of the patient's presenting complaint, an electrodiagnostic med
their firing rate, and additional MUAPs are recruited. A moder icine impression can be formulated. The impression may be
ate muscle contraction usually results in a significant number of simple (e.g., median nerve entrapment in the carpal tunnel) or
MUAPs on the CRT screen limiting individual MUAP analysis. complex (e.g., peripheral neuropathy combined with a radicu
Moderate to maximal contraction is recommended by some in lopathy) and should not only explain the patient's symptoms,
vestigators to evaluate the resulting overlap of multiple MUAPs but assist in the patient's management. This impression is a
known as the interference pattem. 128 The information gained result of the practitioner's expertise regarding the electric find
from an interference pattern is minimal in the authors' opinion. ings and their association with specific disease entities affecting
The extent to which an individual can obliterate the CRT base nerve and muscle tissue. The electrodiagnostic medicine practi
line is dependent upon multiple factors: patient effort, pain, tioner's impression should also be supported with appropriate
ability of the examiner to resist the muscle's contraction, and recommendations regarding prognosis, and if requested, treat
possibly other factors. It is the authors' belief that all of the nec ment options.
essary information regarding MUAP morphology and recruit
ment (see "MUAP Recruitment [Normal Muscle]" below) can
be evaluated at minimal to moderate muscle contraction for the ELECTRICAL ACTIVITY IN MUSCLE
majority of conditions. One exception to this statement would
be a type II fiber atrophy (e.g., steroid myopathy) in which nor Performance of the needle electromyographic portion of the
mally large MUAPs would be absent at maximal contraction. electrodiagnostic medicine evaluation requires a prerequisite
This finding could not be observed if only minimal to moderate knowledge of muscle tissue electrophysiology. Action potential
contractions were investigated and is essentially the only time generation in a volume conductor with its associated extracellular
the authors evaluate maximal contraction. 128 If one pursues waveform morphology is the fundamental knowledge necessary
moderate to maximal muscle contraction, however, it is neces to appreciate normal and abnormal needle electromyographic
sary to ensure superficial needle placement in the muscle to findings. Once single muscle fiber waveform generation is un
avoid bending the needle within the muscle and concomitant derstood, voluntary and spontaneous (nonvoluntary) normal and
tissue trauma. 112 pathologic electrical activity arising from single muscle fibers
can then be appropriately interpreted. Mastery of this information
INFORMATION SYNTHESIS forms the foundation upon which to formulate an appropriate
diagnosis, prognosis, and treatment plan. The electrophysiology
The needle electromyographic investigation is only one part of of muscle and single muscle fiber action potential morphology
the electrodiagnostic medicine evaluation and is directed by the in volume conductors will be briefly reviewed below. The
history and physical examination. As one proceeds through the reader is referred to Chapter 2 for a more detailed explanation
needle examination (and all other portions of the electrodiagnostic of volume conductor theory.
262 - PART II BASIC AND ADVANCED TECHNIQUES
Membrane
ing membrane potential is depolarized from -80 mV to about
Inside
-50 to -60 mY, threshold level, following an appropriate stimu
lus, an action potential is produced (Fig. 7_2A).13·21.130 The
action potential arises from an alteration in voltage-gated chan
nels controlling the permeability of Na+ and K+. At threshold,
B the sodium voltage-gated channels open allowing Na+ to enter
------. H-++++H-++++ PotassiumEfi the excitable tissue and further depolarize the cell thereby in
------:
Sodium Influx?
+ ...... + ++:'::
t iH-++++H-++++
• i
t-- - -
;
-~---- ++++ ducing more sodium gates to open in a positive feedback loop
Nai, : K
that approaches the equilibrium potential of Na+ (+55 mV), This
! process of depolarization lasts about 0.5 ms in mammalian
muscle cells and propagates along the muscle fibers constituting
A i I !
an action potential. 174.175 The cell's resting membrane potential
+ depolarizes from -80 mV to approximately +40 mV l30 A de
o ------- ----r----- L________________ _ layed increase in K+ permeability lasting about 2.0 ms in mam
Em ! ....... i' malian muscle coupled with inactivation of the sodium gates
jl \ , subsequently restores the resting membrane potential back to
,I ' \ •.. .:,
it i .'C' i .......
-80 m y'1I4.174,222 The cell, therefore, produces a positive mono
, i" \ : ... phasic intracellular action potential beginning at -80 mV, in
I ~ l' \: ··· ... ...,r-9
I : . .• \ ', ...... K creasing to about +40 mY, and returning to-80 mV (Fig. 7-2A).213
9 Ii .......•• j 'V9Na ......
o I.- .... ...r. 1 ... The action potential's appearance as characterized by its ampli
tude, duration, rapid rise and relatively slow baseline return is
Figure 7-2. A, Intracellular action potential arising from an increase directly dependent upon the temporal aspects of Na+ and K+ ac
in sodium (gNa+) and potassium (gK+) conductance. B, Region of tivation and inactivation. l69
transmembrane ion flow associated with opening of voltage-depen
dent ion gates. C, Local circuit currents generated by the opening of Local Circuit Currents
sodium gates. D, Extracellular triphasic single muscle waveform gener The impermeable protein anions located within excitable tis
ated by the monophasic intracellular action potential. sues attract extracellular positive ions, primarily Na+ because of
its abundance, and cause them to align along the extracellular
ELECTROPHYSIOLOGY OF MUSCLE surface of that cell's membrane. In effect, there is a series of
negative and positive charges (dipoles) along the length of the
Action Potential Generation cell separated by the plasma membrane (Fig, 7-2B). During the
All living cells possess the unique characteristic of a resting course of an action potential, inwardly flowing positive Na+ pro
membrane potential with the intracellular region electrically ceed bi-directionally along the axon's interior. These additional
negative (approximately -80 mV for muscle tissue) compared intracellular positive charges balance a portion of the intracellu
to the extracellular space.13.130.222 The cell's membrane is respon lar anions attracting the extracellular Na+. The transmembrane
sible for developing and sustaining a transmembrane voltage electrical attraction for the Na+ is subsequently reduced, allow
difference because of its semipermeable nature. Most cells con ing these ions an increased degree of freedom to move away
tain a high intracellular concentration of positive potassium ions from the immediate vicinity of the membrane. The increased
(cations) and negative protein ions (anions). In the resting state, penneability of the depolarized membrane region with its open
the semipermeable membrane allows intracellular potassium sodium gates permits those more mobile Na+ to now enter the
ions (K+) to exit the cell down a high intracellular to low extra cell through the open Na+ channels. This sequence of events is
cellular concentration gradient. 13•13o This process continues until referred to as a local circuit current; it specifically encompasses
it is balanced by an inward electrical attraction from the intra extracellular Na+ entering the cell and neutralizing the trans
cel1ular protein anions that cannot exit the cell. A net negative membrane attraction toward additional extracellular Na+ thereby
charge results when a balance is established between the forces allowing these ions to move away from the membrane's surface
driving K+ out of the cell (concentration gradient) and an in and also enter the cell through the open sodium channels. 15•130
wardly directed force (electrical gradient) from the anions at The extracellular Na+ that are no longer tightly bound to the mem
tracting the K+ into the cell. The resting membrane potential is brane's surface can now enter the cell through the local circuit cur
also influenced to a small degree by the relatively impermeable rent and are referred to as a current source. The region of membrane
positive sodium ions (Na+). There are two strong forces driving through which the sodium ions enter the cell (open Na+ voltage
sodium into the cell. The first is the concentration gradient, high dependent gates) is called a current sinkY·I30 The source current
extracellular and low intracellular Na+ concentration, and the will tend to depolarize the adjacent membrane regions surround
second is the negative intracellular potential or electrical gradient. ing the current sink by reversing the intracellular-to-extracellular
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 263
,
R: Analysis of the distribution of action
.... ....
currents of nerve in volume conductors.
Stud Rockefeller Inst Med Res 1947;
132:384-477.)
"\
\
I ,,
..
1 f ""j
"
"'yll
I
voltage relationship. The self-sustaining nature of these processes negative sink, but still within the region of the current source, now
results in action potential propagation. detects isopotentiallines with less positive magnitude than pre
The current sink from a propagating action potential permits viously measured. The CRT trace demonstrates a corresponding
positive sodium ions to extend not only into that portion of less positive deflection and begins heading toward the baseline.
nerve or muscle previously depolarized, but also into the region When the first zero isopotential (0 1 Fig. 7-3) line demarcating
of the tissue about to be depolarized. Extracellularly, the sodium the leading current source and sink is reached, the CRT trace
ions are moving into the sink from portions of the volume con crosses the baseline, denoting zero potential difference.
ductor both preceding and following the traveling action poten Placing the electrode just to the right of the first zero isopoten
tial. In effect, there are two local circuit currents associated with tialline (Fig. 7-3) now allows it to observe isopotentiallines of
the current sink. 13,I30 This observation leads to the common de rather low magnitude and negative potential. The CRT trace then
scription of an action potential consisting of a "source-sink proceeds above the baseline now describing a negative potential
source" (+ - +) arrangement. l94 (sodium activation/depolarization). As this region contains a
high spatial gradient of field lines, slight electrode progression
Local Circuit Model of Waveform Morphology measures field lines of rapidly increasing negativity (Fig. 7-3).
Lorente de N6 155 provided us with a detailed mapping of the The CRT trace quickly rises above the baseline. Again, as the
field lines surrounding a propagating nerve action potential in a middle region of the negative sink is reached, there is a region
volume conductor (Fig. 7-3). For this discussion, the similari where little change in the isopotentia] magnitude occurs over
ties between local circuit currents of nerve and muscle are more time and the CRT trace now defines the second inflection point
alike than different. The primary distinction between muscle or maximum negative amplitude (Fig. 7-3). Continued progres
and neural tissue is that depolarization/repolarization is approx sion allows the electrode to measure isopotential lines with a
imately 5 times longer in muscle.89.90.m.1I4.156.174.17S To assist in declining negative magnitude that is reflected in the CRT trace
the understanding of extracellular waveform morphology gen returning to baseline (sodium inactivation and potassium activa
eration, we may assume that an action potential and the isopo tion: repolarization). The second baseline crossing occurs when
tentiallines (regions of equipotential extending into the volume the electrode encounters the second zero isopotentialline (02
conductor) associated with the local circuit currents on the sur Fig. 7-3), noting the negative sink's tenninal portion.
face of a single muscle fiber are stationary or "frozen" in time Upon entering the trailing current source (positive region),
(Fig. 7_3).5.76 Note the extracellular potential field lines consti isopotential lines of increasing positivity produce a second
tute a central current sink (negative) flanked by a leading and downward deflection of the CRT trace below the baseline (Fig. 7-3).
trailing current source (positive) for the familiar tripole (+ +).6.71 The waveform's third inflection point is described as the rela
A recording electrode can then be sequentially moved through tively extended region of positive potential and demarcates the
the isopotential field lines associated with the muscle's action maximum amplitude of the potential's third phase. Note that the
potential. Initially (Fig 7-3, far left), the electrode encounters spatial gradient is rather low and spreads out over a compara
positive isopotentiallines with rather low voltage and low spa tively longer spatial extent than the initial source and subsequent
tial gradient (lines per unit distance) of the leading current sink (Fig. 7-3). The amplitude of the third phase is correspond
source. The positive potential results in a downward (positive) ingly smaller and longer in duration. Finally, as the electrode
motion of the cathode ray tube (CRT) trace (Fig. 7-3). Con reaches the terminal portion of the trailing current source, posi
tinued electrode movement detects isopotentiallines of increas tive isopotential lines of low magnitUde result in the CRT trace
ing positive magnitude and the CRT trace proceeds in the more returning to baseline. The net result of this negative current sink
positive direction. At about the middle of the leading current flanked by two current sources in a volume conductor such as
source, the isopotential region is now rather constant and the the body is a triphasic potential (Figs. 7-20 and 7-3). Single
CRT trace maintains the same level for a relatively brief time muscle fibers should, therefore, produce triphasic waveforms in
describing the waveform's first inflection point and demarcat good volume conductors such as the human body. An alterna
ing the maximum amplitude of the first or initial positive de tive and more detailed explanation of action potential morphol
flection. Displacing the recording electrode still closer to the ogy in volume conductor is provided in Chapter 2.
264 - PART II BASIC AND ADVANCED TECHNIQUES
NEEDLE INSERTIONAL ACTIVITY Figure 7-4. Insertional activity. A. Normal insertional activity re
sulting from a brief needle electrode insertion. B, Decreased inser
Placing a needle (monopolar or standard concentric) recording tional activity noted in fibrotic muscle tissue. C, Increased insertional
electrode into healthy muscle tissue and advancing it in quick, activity as routinely described by most practitioners. A large burst of
but short intervals results in brief bursts of electrical potentials electrical activity is associated with needle movement immediately fol
(Fig. 7-4A). A crisp sound is associated with needle movement lowed by florid positive sharp waves and fibrillation potentials that
as a series of negative and positive spikes are produced. These eventually result in a quiet baseline over the course of several hundred
waveforms are referred to as insertional activity and this term milliseconds to seconds.
was first introduced into the standard needle electromyographic
examination by Weddell et al. 231 The observed electrical activity is the basis for the synonymous term of "injury potentials." The
is believed to result from the needle electrode mechanically de duration of insertional activity was quantified in the needle ex
polarizing the muscle fibers surrounding its leading edge as it amination performed by clinicians practicing electrodiagnostic
pierces and pushes aside muscle tissue. l40 Minimal and localized medicine.233 The total time of activity, from the initiation of
muscle tissue damage may occur from direct needle trauma and electrical potentials and extending beyond needle movement
cessation, is less than 230 ms for monopolar needle electrode
Table 7-2. Insertional Activity,s4 insertion distances of 1-5 mm. The time of electrical activity
persisting after needle cessation has a mean of 48 ± 18 ms.232-234
Type Duration Shape Etiology The total time of insertional activity for standard concentric
Normal < 300 ms Spikes Muscle depolarization needles is reported to be less than 300 ms (Table 7-2).l(J9
Increased > 300-500 ms Spikes Normal variant The purpose of including insertional activity analysis as part
Positive waves Normal variant of the electromyographic examination is that the probing needle
Denervation may provoke transient and/or sustained membrane instability
Myopathy (fibrillation potentials and positive sharp waves: see below) prior
to these potentials being present at rest. Wiechers et al.232 clearly
Decreased Absent or Absent/spikes Fat
demonstrated in a denervated animal model that positive sharp
< 300 ms Fibrosis
waves are the fIrst sign of membrane instability followed by fib
Periodic paralysis
rillation potentials. This early membrane instability resulted only
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 265
ZONE
Once again, the location of the needle electrode is associated
with patient discomfort, and pushing the needle through this
AWAY
area usually results in considerably less pain. It is possible to
mistake endplate spikes for fibrillation potentials (see be](?w),
which are also single muscle fiber discharges, The highly irreg
ular firing rate of endplate spikes usually distinguishes these po
tentials from fibrillation potentials. The cannula's tip of a
standard concentric needle electrode placed in the endplate zone
a 100 200 may produce endplate spikes with an inverted polarity (bipha
TIME (ms) sic: positive/negative; Fig. 7-6) possibly leading to confusion
with positive sharp waves (see beIOW)}28,217 Again, the highly ir
Figure 1-6. Endplate electrode artifact. MEPPs recorded with a regular firing rate should alert one to the possibility of endplate
standard concentric needle electrode (top trace) may become in spikes. As previously stated, the needle recording electrode
verted with respect to polarity if these same potentials are preferen should be relocated if it is in the endplate zone to avoid patient
tially recorded with the needle's cannula (reference electrode). (From discomfort and waveform morphology confusion, Endplate
Brown WF: The Physiological and Technical Basis of Electromyography. spikes will also not be detected following denervation for simi
Boston, Butterworth, 1984, pp 317-368, with permission.)
lar reasons to those given for MEPPs,
Several investigators have suggested that endplate spikes may
Endplate Spikes (Biphasic Negative/Positive arise from the intrafusal muscle fibers (muscle spindles) inner
Waveform) vated by gamma motor neurons. 179 Although it is certainly pos
A needle recording electrode situated in the endplate region sible that intrafusal muscle fibers may be a source of
can detect a second spontaneous potential with a different mor spontaneous electrical activity, it is doubtful that they produce
phoogy than the MEPP. This second potential is biphasic with an the commonly encountered endplate spikes associated with
initial negative deflection and referred to as an endplate spike (see MEPPs. The reasoning for this conclusion is that endplate
Chapter 2 for a more complete discussion of this potential's mor spikes and MEPPs are frequently found in combination,20 There
phology). Compared to the MEPP, the endplate spike is longer is no question that MEPPs are generated in the endplate, Slight
in duration (3-5 ms), of moderate amplitude (100-200 ~V), and needle electrode movement typically produces endplate spikes,
fires irregularly (Fig. 7-5, Table 7-3).32 It is important to note that strongly suggesting that both potentials are produced from the
endplate spike potentials may also have a triphasic initially pos same location, i.e., extrafusal and not intrafusal muscle fibers.
itive shape, a biphasic initially positive morphology and even Also, investigators have not detected an alteration in the firing
rather complex configurations resembling a combination of the of endplate spike potentials following passive stretch or volun
two previously noted waveforms.The first of these less proto tary activity which should occur if the muscle spindle produces
typical appearances may be mistaken for a fibrillation potential endplate spikes. 21
while the second may be misinterpreted as a positive sharp
wave. SO Additionally, on rare occasions irritation of a single or a
few terminal nerve sprouts may induce the terminal nerve's MUSCLE GENERATORS OF NORMAL
parent motor unit to fire, revealing an irregular firing motor unit VOLUNTARY ACTIVITY
potential. The key to properly interpreting these waveforms is
paying particular attention to the irregular firing rate. SINGLE MUSCLE FIBER (TRIPHASIC WAVEFORM)
The endplate spike is thought to be a suprathreshold single
muscle fiber depolarization that propagates away from the Depolarization of a single muscle fiber results in a triphasic
recording electrode. It originates from the endplate zone and re extracellular waveform when recorded outside of the endplate
sults from the recording needle electrode irritating the single zone (Fig. 7_7).64.87 This triphasic potential may appear biphasic
muscle fiber's terminal axon or the presynaptic terminal (negative/positive) if the needle recording electrode is located
itself. 32,237 This irritation produces substantially more acetyl within the endplate region,20B A biphasic positive/negative
choline release than in the generation of MEPPs resulting in a single muscle fiber potential may also be observed under three
suprathreshold depolarization of the muscle fiber. 20 ,236 Just as conditions. The first condition producing a biphasic posi
tive/negative single muscle fiber potential arises when the termi
nal positive phase is rather small and lost in the baseline noise of
~200p.V the recording,S? In reality, the potential is triphasic, but the third
phase is prolonged and small enough to be mistaken as part of
Ims the baseline irregularity. A recording electrode within the mus
culotendinous region is the second condition where an initially
positive biphasic single muscle fiber potential can be recorded. 129
Finally, if the cannula's tip of a standard concentric needle elec
trode is placed in the endplate zone, a suprathreshold initially
negative biphasic potential following endplate depolarization is
inverted to produce a positive/negative waveform. 128.135 A de
Figure 7-7. Two triphasiC single muscle fiber waveforms belong tailed volume conduction description of the above potentials is
ing to the same motor unit recorded from a normal extensor digito provided in Chapter 2, A separate component of the electrodiag
rum communis muscle. nostic medicine consultation which exclusively focuses on the
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 267
single muscle fiber action potential, single fiber electromyogra Type II motor neuron
phy (SFEMG) will be discussed later (see Chapter 8).
Type I16bel
Anatomy
The concept of the motor unit was introduced by Sherrington Figure 7-B. Two motor units (type I and II) are depicted. Note
over 60 years ago. 202 The motor unit is the fundamental or quan how fibers from one motor unit are interspersed with those from an
tal element which forms the foundation upon which the nervous other motor unit. (From Oh SJ: Clinical Electromyography: Nerve
system exercises control over muscle tissue to produce move Conduction Studies, 2nd ed. Baltimore, Williams &Wilkins. 1993, with
ment. The motor unit is defined as one anterior hom cell (mo permission.)
toneuron), its peripheral nerve, and all of the individual muscle
fibers innervated by that individual motoneuron (Fig. 7-8). innervated by only one motoneuron, i.e., there is no polyneu
There are three types of motor neurons identified: alpha (skele ronal innervation in adult humans. Occasionally two neuromus
tomotor) motor neurons, beta (skeletofusimotor) motor neurons, cular junctions may be observed on a single muscle fiber;
and gamma (fusimotor) motor neurons. 161 The alpha motor neu however, both endplates originate from the same motor axon. It
rons consist of large cell bodies and fast conducting axons that is possible to estimate the number of muscle fibers innervated
only innervate the skeletal (extrafusal) muscle fibers. Alpha by one motoneuron, i.e., the innervation ratio.35
motor neurons are located in the ventrolateral horn (lamina IX, The innervation ratio can be calculated by painstakingly
Rexed classification) of the gray matter within the spinal counting the total number of muscle fibers in a particular
cord. 192 The motor neurons innervating a particular muscle are muscle and dividing by the number of large motor axons inner
clustered into vertical columns extending for a finite distance vating that muscle. The number of large motor axons in a pe
over one spinal segment. Additionally, the motor neurons inner ripheral nerve associated with a muscle is approximately 50%
vating the limbs are situated relatively laterally in the spinal with the remainder primarily consisting of afferent fibers. 81 ,82.239
cord's cervical and lumbar enlargements compared to the motor Muscle fiber numbers in motor units vary within one anatomi
neurons innervating the neck and trunk muscle. 14 It has been cally defined muscle and between different muscles. Generally,
demonstrated that the cell soma of the alpha motoneuron is
completely covered with synaptic connections to other cells Cal MNP4
except for the axon hillock which gives rise to the axon. Axon
MG - N' 337
FLEXOR HALLUCIS
LONGUS
6,3 Hz 10 Hz
SOLEUS
SOOms
Recruitment Principles
A physiologic property of motor units closely related to those
noted above is recruitment. Recruitment may be defined as: "The
successive activation of the same and additional motor units
with increasing strength of voluntary muscle contraction."l The
central nervous system can increase the strength of muscle ~on
traction in three ways: altering the number of active motor units,
changing the rate at which individual motor units fire to optimize
the summated tension generated, or combining the first two
mechanisms. 35 ,46.204 Within rather general terms, motor units are
recruited in a relatively constant manner according to their size
and the amount of tension they can generate. When a muscle is
initially activated, the first motor units to fire are usually the
weakest as defined by the tetanus tension. With an increasing
strength of contraction, larger motor units are called upon to
fire, The result is a not only an orderly addition of sequentially
largerl"stronger" motor units but also a smooth increase in
strength. The orderly recruitment of sequentially larger motor
units is referred to as the Henneman size principle described by
Henneman et aL 116,117 The order in which individual motor units
are recruited is not fixed, but can vary depending upon the type
of movement induced. 65 Although it appears that the order of re
cruitment may be rather stereotypical for the same movement,
Figure 7~' 3. Three physiologic properties of motor units are
graphically depicted. Note that motor units with relatively large tetanic
the tension for specific motor unit firing varies with the move
tension (;?: 20 gm) may either fatigue rapidly (FF: near 0.0 on fatigue ment's speed.1 00, 11 1As recruitment is one of the major portions of
scale) or display resistance to fatigue (FR: near 1.0 on fatigue scale). the needle electromyographic examination, it will be reviewed
Both of these motor units have short-twitch tension times. A third in detail with respect to normal and abnormal findings below,
motor unit type can have low tetanus tensions « 20 gm) but is resis
tant to fatigue (S: 1.0 on fatigue scale).A few motor units, F(int). have Parameters
tetanus tensions> 20 gm, fast twitch times, and intermediate fatigue The MUAP recorded with a needle electrode placed in a vol
properties. (From Burke RE.levine ON. Tsairis P, et al: Physiological untarily contracting muscle arises from the summated electrical
types and histochemical profiles in motor units of the cat gastrocne activity of all the single muscle fibers belonging to a particular
mius.J Physiol 1973;234:723-748. with permission.)
motor unit. For discussion purposes, a single motor unit within
the biceps brachii may be examined (Fig, 7-14). A single muscle
units between FF and FR is denoted F(int). Because contractile fiber in the biceps muscle extends from the origin to the inser
and metabolic properties are related, histochemical techniques tion,30 Each muscle fiber is innervated by only one terminal
reveal that mitochondrial enzymes, succinate dehydrogenase,
have higher activity in fibers that are fatigue resistant while Table 7-5. Motor Unit Characteristics
phosphorylase activity (myosin-ATPase) are high in fibers re
liant on glycolysis, Le., fatigue sensitive (Table 7_5).74 The inter Fast-Twitch Slow-Twitch Fast-Twitch
mediate fibers display metabolic pathways capable of using Oxidative Oxidative Glycolytic
both enzyme systems. (SO) GlycolytiC (FOG) (FG)
As previously noted, it is possible to tease out a single motor General Features
axon and repetitively stimulate it to metabolically drive the Red coloration Dark Dark Pale
muscle fibers belonging to that particular motor unit.12.141,142 Myoglobin High High Low
Staining these fibers for glycogen by using the PAS technique Capillaries High High Low
reveals that all of the muscle fibers innervated by the stimulated Mitochondria High High low
nerve are depleted of glycogen. This finding suggests that Fatigue Very resistant Resistant Sensitive
muscle fibers of different motor units may differ in their meta Twitch speed low Intermediate High
bolic requirements. Indeed, fast-twitch motor unit muscle fibers Tetanic force low Intermediate High
rely on glycolysis for energy while slow-twitch fibers depend Fiber diameter Small Intermediate large
upon oxidative mechanisms. 43,46 An intermediate muscle type Staining Quality
has been recognized that uses a combination of both oxidative PAS (glycogen) low High High
and glycolytic pathways to sustain its metabolic needs. These Phosphorylase low High High
motor unit metabolic characteristics have resulted in a number Myosin ATPase low High High
of classification systems (Table 7_5).15.185 Slow-twitch oxidative SOH Intermediate High low
(SO) fibers are also referred to as type I or B fibers, Fast-twitch
oxidative glycolytic (FOG) motor units may also be called type Other Classifications
IIA, type II, or C. Finally, fast-twitch glycolytic (FG) are also DubowitzlPearse73 II II
known as type lIB, type II, or A. Fast-twitch fibers are sup Brooke/Kaiser 1s IIA liB
ported by few capillaries while slow-twitch motor units are en Stein/Padykula2H B C A
veloped by a rich capillary supply consistent with their Burke43 S FR FF
metabolic requirements. Modified after McComas'·3
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 271
fiber to be activated has the longest terminal axon to neuromus fibers' action potentials will result in a coincident reduction in
cular junction length. Recall that the conduction velocity of the MUAP spike amplitUde. Additionally, larger muscle fibers pro
terminal axon is considerably faster than muscle action poten duce a larger voltage associated with depolarization compared
tial conduction. Even though a particular single muscle fiber to smaller fibers with corresponding MUAP amplitudes.27.28 A
may be activated prior to another because of a relatively short number of instrumentation factors can also affect the MUAP's
terminal axon, its muscle action potential propagates much amplitUde (see Chapter 3). Specifically, a reduction in Mt)AP
slower than a longer neighboring terminal axon. A second ter amplitude can be anticipated if: (I) the high-frequency filter is
minal axon, therefore, may proceed somewhat further to its neu reduced,5C>-58 (2) concentric as opposed to monopolar needles are
romuscular junction which is located at the edge of the endplate used,55.58.'24.m (3) comparatively larger electrode lead off surface
zone for example. If a needle electrode is located near the end is used,88 (5) a concentric needle electrode is rotated (directional
plate's perimeter and closer to the second terminal axon/muscle recording properties),24.25,47 and (6) Teflon from a monopolar
fiber combination, that portion of the MUAP resulting from this needle is removed. 59 The effect of temperature on MUAP ampli
particular single muscle fiber action potential will be observed tude is somewhat controversia1.57.124 Both amplitude reduction
prior to that of the muscle fiber excited earlier. This is because and elevation have been reported with a decrease in muscle tem
the terminal axon's conduction velocity is faster than that of ini perature.10.25.61It is the authors' opinion that MUAP amplitude
tially activated single muscle fiber which is further from the increases with temperature reductions initially, but as the tem
recording electrode. In summary, the net MUAP duration is the perature continues to decline, action potential failure occurs re
electrical summation of all muscle fibers' action potentials com sulting in MUAP amplitude reductions. MUAPs recorded in
prising one motor unit. persons greater than 65 years in general are slightly larger than
Phase. The MUAP phase is simply defined as that portion of those recorded in younger individuals. 25.55
a potential between CRT trace baseline departure and return MUAP duration is directly proportional to the width of the
(Fig. 7-15).1.212 The number of CRT baseline crossing plus one endplate zone and to a lesser extent the terminal axon conduc
yields the total number of MUAP phases. For example, if the tion velocity.25.21,28 Elevating the low-frequency filter will
MUAP crosses the CRT baseline twice, the MUAP is triphasic. remove the low-frequency content of the MUAP, initial and ter
This is the usual appearance of most MUAPs. Normal MUAPs minal phases, thereby reducing the duration. 58 Concentric
have 4 or fewer phases and MUAPs with 5 or more phases are needle electrodes may reduce the MUAP duration somewhat,
said to be polyphasic.! A small percentage of the total number although this is debatable. Cooling of the muscle produces an
recorded normal MUAPs are polyphasic depending upon the increase in MUAP duration.lo.25.61
needle electrode: monopolar (up to 30%) or concentric (up to The number MUAP phases is contingent upon the motor
15%). As previously stated, the main spike component of the unit's single muscle fiber action potential's degree of asynchro
MUAP is believed to arise from one and possibly fewer than 12 nous passage past the recording needle's active surface. The
single muscle fibers in very close « 500 11m) proximity to the greater the degree of synchronicity, the fewer the number of
needle electrode's recording surface.27.28.I05-107 The remaining phases, while greater temporal dispersion among the single
single muscle fiber action potentials located at some distance muscle action potentials increases the number of MUAP phases.
(> 500 J.1m) will be propagating toward, and away from the Factors such as aging and temperature reduction will increase
needle electrode prior to and following the formation of the the MUAP's number of phases. Elevating the low-frequency
MUAP spike. Recall from volume conduction that (l) muscle filter may also result in a greater degree of phasicity.58 Mono
tissue acts as a low pass filter and (2) single muscle fiber action polar needle recordings may have MUAPs with a higher per
potentials are triphasic. 87.88 The muscle tissue surrounding the centage of polyphasic potentials. 55
needle electrode filters out most, but not all, of the negative Recruitment (Nonnal Muscle). The physiologic principles
spike components of the action potentials arising from neigh governing the orderly recruitment of motor unit action potentials
boring muscle fibers belonging to the activated motor unit. has been briefly described above. 116.1 17 We will now turn to the
Following filtering, what remains is the low frequency initial practical assessment of MUAP recruitment during the electro
and terminal positive phases and a small negative spike of the diagnostic medicine examination. It is important for the practi
triphasic action potentials. These "distant" potentials' phases tioner to keep in mind that motor unit recruitment is a poorly
help form the initial and terminal positive phases and, to a small understood process and only a very simple explanation will be
degree, the negative phase of the nearby spike potential. The provided in this section as it pertains to the electrodiagnostic
spike portion of the MUAP also has its own initial and terminal medicine consultation. Several assumptions will be made to
positive phases. In the volume conductor, the net summation of both simplify the discussion and maintain its relevance to practi
these positive and negative waveforms depends upon the loca cal needle electromyography. Specifically, we will assume that:
tion of the needle electrode with respect to the single muscle (1) the first recruited MUAPs arise from the small and relatively
fibers; they all contribute to forming the various phases of the slow conducting type I motor units (see above) exclusively,35,46.'83
MUAP (see Chapter 2). (2) only minimal to moderate effort will be expended by the pa
Variations of Parameters. The amplitude, duration, and tient (depending upon the strength of the muscle), (3) later re
phases of normal MUAPs can vary depending upon several non cruited motor units (type II) will simply not be capable of being
pathologic variables. Maximum MUAP spike amplitude is pri analyzed, (4) subtle pathology affecting only a small portion of
marily influenced by the distance between the electrode's the muscle may be missed, (5) the first motor unit to fire con
recording surface and the electrical generator. As previously tinues to increase its firing rate with more force generation, and
noted, 90% or more of a potential's amplitude may be dimin (6) slow and constant contraction will be sufficient to demon
ished by displacing the electrode more than 500 J.1ffi away from strate motor unit recruitment abnormalities.182-'84
the active tissue's surface.l°5- 107 Amplitude is also directly re Equipment. There are no generally accepted parameters for
lated to the total number of synchronously active fibers near the evaluating MUAP recruitment. These authors use amplifier low
electrode. Decreasing the synchronous arrival of single muscle frequency filter settings of 10-30 Hz and a high-frequency filter
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 273
range of 10,000 Hz or more. A sensitivity capable of resolving Table 7.7. Human Muscle Recruitment
the entire potential is typically used and ranges from 100 to Onset Onset Recruitment Recruitment
1000 J.l V/div. A sweep speed of 20 ms/div suffices for most pur Interval Frequency Interval Frequency
poses. Either a monopolar or standard concentric needle elec Muscle (ms) (Hz) (ms) (Hz)
trode can be used.
Technique. In attempting to analyze MUAP recruitment one Facial Muscles
must realize that the main goal is to identify the first few re Frontalis 102 ± 29 9.8 46 ± 17 21.7
cruited motor unit's action potentials and measure their firing Orbicularis oris 70± 19 14.3 34 ± 10 29.4
rate. Although this may sound like a simple task, some practice All facial muscles 86 ± 29 11.6 40 ± 16 25.0
and patient cooperation are required to assess MUAP firing fre Upper Limb Muscles
quencies in a time-efficient manner. The beginning practitioner Deltoid 116± 23 8.6 84± 16 11.9
should practice this analysis on a limited basis in normal muscle Bicep 124±21 8.1 86± 14 11.6
tissue prior to investigating pathological muscle. Tricep 132± 16 7.6 84± 17 11.9
MUAP recruitment may be examined before the needle elec Brachioradialis 116 ± 22 8.6 78± 18 12.8
trode is withdrawn from the muscle under investigation just fol Pronator teres 132 ± 38 7.6 SS± 19 11.3
lowing the routine needle study. The patient is instructed that 1st dorsal 142 ± 39 7.0 98± 21 10.2
only a gentle contraction of the musc1e is required and state interosseous
ments such as " ... just think about contracting the muscle ..." Paraspinal Muscle
are often used. One would like to detect just one motor unit Multifidus I 52 ± 33 6.6 102 ± 20 9.8
firing regularly. Motor units usually begin firing irregularly at
Lower Limb Muscles
2-3 Hz and then achieve a stable and regular firing rate at 5-7
Gluteus maximus I 28 ± 30 7.8 SS± 16 11.4
Hz.35,n,182-184 The patient is then asked to increase the force of
Vastus lateralis 126 ± 30 7.8 88± 18 11.4
contraction minimally. The first recruited MUAP (MUAP A)
Biceps femoris 132 ± 29 7.6 92 ± 16 10.9
should then increase its rate of firing to between 6 Hz and 10Hz
Tibialis anterior 124 ± 26 8.1 90 ± 13 11.1
(Table 7-6). More force is usually generated initially by increas
Medial gastroc- 156 ± 29 6.4 110 ± 23 9.1
ing the firing frequency of the first recruited motor units. With a
nemius
continued modicum of increased force, the first recruited 7.2
EDB 138 ± 29 98 ± 13 10.2
MUAP eventually achieves a firing rate of about 10 Hz. At this
AI/limb 132 ± 32 7.6 90 ± 19 ILl
frequency, a second motor unit is recruited (MUAP B; Tables 7-6
muscles
and 7-7). The frequency of MUAP A when MUAP B just begins
to fire regularly is called the recruitment frequency.! Although it Modified after Petajan. l82, 184
takes some practice, the physician can recognize this event by
(1) observing the screen for a second motor unit to appear and its morphology may be altered. Care must be exercised, there
(2) listening for the change in sound associated with two fore, to ensure that the same MUAP from one motor unit is cor
MUAPs firing. The authors find the sound of the second motor rectly identified for time marker placement. The examiner and
unit to be most helpful. Once this sound is detected, the instru patient may require practice before mutual understanding arises
ment's footswitch is depressed to "freeze" the screen. The la as to what is needed to measure MUAP recruitment intervals
tency markers are positioned on two sequential MUAPs from and frequencies. Several (4-5) regions of the muscle under ex
MUAP A just before MUAP B appeared. This time difference is amination may need to be studied to gain a representative
called the recruitment interval, I the reciprocal of which yields sample of recruitment frequencies.
the recruitment frequency. Most normal muscles in humans To simplify the discussion regarding motor unit recruitment
have a recruitment interval of 100 ms with a recruitment fre in the normal situation and to lay the groundwork for abnormal
quency approximating 10Hz (1 motor unitllOO ms = 10Hz; recruitment, we will assume that the first several motor units
Table 7-7). Facial muscles have a somewhat shorter recruitment follow the above described simple rule of increasing firing rate.
interval and corresponding higher recruitment frequency. Let us return to our patient in which the first recruited MUAP
The "trick" in the above relatively straightforward procedure (MUAP A) is firing at 10Hz and the second (MUAP B) is firing
is to accurately identify sequentially firing motor units. With a at 5 Hz (Table 7-6). If the patient is requested to increase the
sweep of 20 ms/div, the MUAP is somewhat "compressed" and force production slightly, MUAP A will incrementally increase
its firing rate as will MUAP B. When MUAP A reaches 15 Hz
Table 7·6. Normal Recruitment and MUAP achieves a firing rate of 10Hz, a third motor unit
(MUAP C) begins to fire at about 5 Hz. To continue this process
Motor Unit Recruited
one more step, a further increase in muscle force production re
1st (A) 2nd (B) 3rd (C) 4th (D)
sults in the following firing frequencies: (1) MUAP A: 20 Hz,
A (5 Hz) (2) MUAP B: 15 Hz, (3) MUAP C: 10 Hz, and (4) the addition
A (10 Hz) B (5 Hz) of a fourth motor unit represented electrically by MUAP D
A (15 Hz) B (10 Hz) C (5 Hz) firing at 5 Hz (Table 7-6). Again, the sequential addition of
motor units is considerably more complex than illustrated above
A (20 Hz) B (15 Hz) C (10 Hz) 0(5 Hz)
and may not exactly follow this sequence. However, normal and
MUAP A begins firing stably at about 5 Hz.With a minimal increase in force of pathologic physiologic conditions can be conceptualized
muscle contraction. MUAP A increases its firing rate to 10Hz and MUAP B through this simple example.
begins firing stably at 5 Hz.The recruitment frequency for this muscle is 10Hz.
A still further increase In contraction causes MUAP A to fire at 15 Hz. MUAP B Although the firing frequencies noted above are rough ap
fires at 10Hz. and a new motor unit (MUAP C) is activated.This process con proximations, they can be used to formulate a few simple con
tinues as noted for MUAP D. cepts that may be used to characterize the normal recruitment of
274 - PART II BASIC AND ADVANCED TECHNIQUES
MUAPs identified on the CRT screen. The orderly recruitment abnormalities as observed in attacks of periodic paralysis
of the four motor units above can be discussed in terms of the (Table 7-2). Necrotic muscle resulting from profound ischemia
rules of five,63 i.e., motor units begin firing at stable rates of also produces little electrical activity. The author has observed
5 Hz. When the first motor unit to fire reaches 10Hz, a second that improper electrode amplifier connections may simulate de
motor unit is activated and fires at 5 Hz. Each time a motor unit creased insertional activity. Inadvertently connecting the needle
is recruited, 5 Hz is serially added to each MUAP firing fre electrode lead to the ground port while the ground and refer~nce
quency already present (Table 7-6). Using the MUAP firing rate leads are placed into the active and reference amplifier ports re
and number of different motor units on the CRT screen, one can spectively will result in a satisfactory baseline, but on inserting
formulate a recruitment ratio. Specifically, the frequency of the the needle minimal insertional activity is observed, erroneously
fastest firing MUAP divided by the number of different MUAPs producing the appearance of fibrotic muscle. A quick check on
on the screen should result in a number close to 5 (fastest the electrode connections will rectify this instrumentation
MUAP/# MUAPs = 5).63 In the above example, 4 separate motor error.
units were activated when the highest MUAP frequency ap Increased Insertional Activity. Following the insertion of a
proached 20 Hz. The recruitment ratio is 5 (20/4 = 5). If this needle electrode into normal muscle tissue, electrical activity
number approaches 10, then there are too few motor units for the persists for approximately 50 ms after the cessation of needle
greatest firing frequency and force produced. Similarly, if this movement. 232- 234 Electromyographers have noted that inser
number is reduced below 4 or 5, then there are too many motor tional activity may appear to be prolonged in a number of patho
units for the highest firing ['dte. The recruitment ratio can also be logical conditions. This finding has led to the term "increased
used to predict the number of MUAPs that should be present insertional activity" which is believed to designate abnormal
given the firing rate of the fastest MUAP. Simply, suppose a potentials after needle movement has stopped but before the
MUAP's frequency is 15 Hz. Dividing this number by 5 suggests occurrence of sustained spontaneous potentials (Fig. 7-4C,
that three separate MUAPs should be present on the CRT screen. Table 7_2).109.151 In disease states where the muscle is no longer
A last concept to consider is predicting the firing rate of innervated, the increased insertional activity supposedly com
MUAPs by looking at the CRT screen if the sweep speed is pletes a temporal continuum from the previously normal inser
known. In the above examples, how many times will a motor tional activity to the development of sustained membrane
unit firing at 20 Hz appear on the CRT screen? If the sweep instability. A controlled study investigating the duration of
speed is 10 ms/div, there are lOOms across the entire screen (10 muscle depolarization following needle movement in dener
ms/div x 10 div/screen 100 ms/screen). A motor unit firing at vated muscle did not substantiate abnormalities in insertional
20 Hz means that it is firing 20 timesll second or 20 timestl ,000 activity.232 The time period of 50 ms was the same for both the
ms. If it is firing at 20 times/l,OOO ms, this is the same as I denervated and control muscle tissue despite significant mem
time/50 ms. If the screen has 100 ms, this motor unit should brane instability. It appears that the concept of increased inser
appear twice every 100 ms or 2 MUAPs per CRT screen (1 tional activity, strictly speaking, is erroneous. Therefore, it may
MUAP/50 ms x lOOms/screen =2 MUAP/screen). Remember be more accurate to state that needle movement actually pro
that this is the same MUAP firing at a frequency that allows it to vokes either sustained or unsustained abnormal spontaneous po
appear twice during the one sweep of 100 ms. As long as the tentials when addressing insertional activity.
sweep is 10 ms/div, one only has to multiply the number of
times the same potential is present on the CRT screen by a Fibrillation Potentials
factor of 10 to arrive at its correct firing frequency. If the sweep In vitro observations reveal that following denervation for
speed is changed to 5 ms/div, the number of times the same 4-6 days or longer, the muscle fiber's resting membrane poten
MUAP appears on the CRT is multiplied by a factor of 20 to de tial begins to approach a less negative level of -60 m V com
termine the MUAP's firing rate. Note that calculating the firing pared to the normal value of -80 mV.82.221-223 Additionally, the
frequency for a particular motor unit is not the same as deter resting membrane potential begins to oscillate. As the "thresh
mining the recruitment frequency. old level" (about -60 mV) producing the all-or-none self-sus
taining action potential and the new resting membrane potential
are now similar, an oscillating membrane potential can eventu
MUSCLE GENERATORS OF ABNORMAL ally reach the membrane's depolarization threshold leveL Once
SPONTANEOUS POTENTIALS threshold is achieved, a propagating action potential is induced
and referred to as a fibrillation potential. 32 The repolarization
INSERTIONAL ACTIVITY phase of denervated muscle results in a temporarily more hyper
polarized (-75 mV or more) level than the new resting mem
Decreased Insertional Activity. Although not examined in brane potential of -60 mY. Additionally, the muscle's
a quantifiable manner, the designation "decreased insertional repolarization then affects the threshold by hyperpolarizing it
activity" may be justified. Muscle tissue that has undergone fi below -60 mY. As the hyperpolarized membrane level (-75 mV
brosis will no longer be capable of electrical activity and hence or more) begins to return toward its resting membrane level of
a decrease in needle insertional activity is noted (Fig. 7-4B). -60 m V (now less negative than the new threshold level e.g.,
The result is little if any electrical potentials detected following -65 m V), an action potential is again produced. This process
needle movement. This tissue may also have a "gritty" or fi regularly repeats on a time interval dependent upon the repolar
brous feel during needle insertion. Obviously, one must ensure ization-to-threshold turnaround time.66.220.221 The regularly oc
that the recording electrode is located in muscle tissue. A needle curring fibrillation potentials fire in a cyclical pattern. That is,
electrode inserted into subcutaneous adipose tissue or tendon they tend to suppress themselves, creating relatively quiescent
will demonstrate minimal electrical activity associated with periodS.153·154.187.188.189 These intervals of quiescent muscle may
needle insertions. One may also detect decreased insertional ac explain in part why fibrillation potentials and positive sharp
tivity in electrically silent tissue due to metabolic/electrolyte waves may be found in abundance at some times and and absent
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 275
Table 7·9. £ ...,,,II,n.. of Fibrillation Potentials'i nerve stimulation by showing an absent response above but
Characteristics not below the presumed lesion site.
Fibrillation potentials and positive sharp waves have also been
o No fibrillation potentials documented in primary muscle diseases (Table 7_8).144.171
1+ Persistent/unsustained single trains in at Although the exact mechanism of membrane instability produc
least two muscle regions tion is poorly understood, a number of proposals have been sug
2+ Moderate numbers in three or more gested. Essentially any muscle fiber deprived of its innervation
muscle areas will fibrillate. 69•7o,222 If the muscle undergoes segmental necrosis,
3+ Many in all muscle regions portions of the muscle fiber may no longer be connected to its ter
4+ CRT baseline obliterated with fibrillation minal axon. In effect, those muscle regions are now denervated.
n"'1'..n1'i"l~ in all areas of muscle examined
This process has been documented in a number of primary
muscle diseases. Also, it may be possible for inflammatory cells,
muscle fibrosis, and fiber splitting to result in the terminal axon
spontaneous muscle fiber depolarization. For example, in the becoming separated from the muscle fiber resulting in a dener
case of a radiculopathy, membrane instability may be ob vated muscle. One can also detect fibrillations in familial hyper
served in the paraspinal muscles within 7-10 days. These kaIemic periodic paralysis during attacks of paralysis. Fibrillation
same abnormal potentials are then seen in the corresponding potentials are either absent or markedly reduced between at
myotomallimb regions in approximately 21 days. If the lesion tacks. 102 The etiology of fibrillation potentials in this disease is
resolves, the membrane instability will first resolve in the most likely a metabolic abnormality of K+ and/or Cl- conduc
paraspinal muscles to be followed by resolution in the limb tance. Any metabolic abnormality adversely affecting the sodium,
muscles. Positive sharp waves and fibrillations may persist for potassium, and chloride ion gates may lead to a situation where
years following an injury resulting in axonal 108S. 136 The the resting membrane potential may become unstable to such a
mechanism whereby this finding occurs is poorly understood. degree as to result in positive sharp waves and fibrillation poten
It may be that some of the denervated muscle fibers become tial generation even in the absence of denervation. Positive sharp
sequestered by connective tissue or other denervated muscle waves and fibrillation potentials are abnormal, but they must be
associated with the denervation process thereby impeding viewed in the context of all the data collected in combination with
reinnervation. "Walled off' regions of muscle surrounded by the history and physical examination.
fibrous tissue are created through which a nerve sprout is A single investigation has suggested that it is easier to detect
prevented from entering. As long as the muscle's vasculature fibrillations potentials and positive sharp waves with a concen
survives, it may continue to fibrillate. Of course, these se tric compared to monopolar needle electrode. 201 This has not
questered muscle fibers will atrophy. Atrophic muscle pro been the experience of the author. On the contrary, it is the au
duces less of a voltage following depolarization, and one thors' experience that fibrillation potentials and positive sharp
could anticipate that these fibrillations and positive sharp waves are detected equally with either needle type, provided one
waves should decrease in amplitude over time. This has indeed is paying close attention to the loudspeaker. It is rather typical to
been found to be the case. The mean fibrillation amplitude hear these potentials prior to seeing them on the CRT. However,
during the first two months following nerve injury approxi one may hear and not see the fibrillation potentiaUpositive sharp
mated 600 flY.136 By the end of the third month the amplitude wave with a concentric electrode while being able to see and
had declined to 500 flV and reached 300 JlV at 6 months. After hear it with the monopolar electrode. As stated elsewhere in this
one year, fibrillation amplitude did not exceed 100 flY. In the book, one needle is not superior to the other; rather they each
authors' opinion, caution should be exercised in using fibrilla have unique recording characteristics which should be taken ad
tion potential following injury to date the implied lesion onset. vantage of.
Considerable more work is required to more fully substantiate
the relationship between fibrillation potential amplitude and Complex Repetitive Discharge
the lesion's ageJ9 Buchthal 36 has attempted to roughly quanti A complex repetitive discharge (CRO) is a spontaneously
tate the amount of fibrillation potentials based on the patient's firing group of action potentials formerly called bizarre high
strength (1-5 scale of Medical Research Council, 1976). The frequency discharges or pseudomyotonic discharges. 92.216 These
incidence of membrane instability was greater in muscle with potentials are not observed by direct visual inspection, but re
significant weakness (force < 4) than muscle with a grade of quire a needle recording electrode be placed into the muscle.
4+ or more. Additionally, in muscle with equal degrees of The morphology of these potentials on needle electromyo
strength there are differences in the amount of membrane in graphic examination are continuous runs of simple or complex
stability depending upon the type of neurogenic lesion. spike patterns that regularly repeat at 0.3-150 Hz (Fig. 7-17;
Attempts to further quantify the degree of fibrillation poten Table 7-10). The repetitive pattern of spike potentials has the same
tials with the amount of nerve loss are not substantiated by ex appearance with t-ach firing and bears the same relationship
perimental data and should not be attempted. Four plus (4+) with its neighboring spikes. A distinct sound likened to heavy
fibrillation potentials do not of themselves suggest complete machinery or an idling motorcycle is produced by the firing of
muscle denervation, but only that a specific region of muscle CROs. In addition to the sound and repetitive pattern, a hall
surrounding the needle electrode is deprived of its nerve mark of these waveforms is that they start and stop abruptly.92.228
supply or metabolically affected in an adverse manner. It is Complex repetitive discharges may begin spontaneously or be
also necessary to attempt to record MUAPs and examine mul induced by needle movement, muscle percussion, or muscle
tiple areas of muscle prior to concluding whether a muscle is contraction.208.210.228 Single-fiber electromyography has provided
completely denervated or not. The possibility that the absence insight into CRD production.
of motor units is due to a complete proximal conduction block Nerve block and curare do not abolish CRDs suggesting that
should alway be contemplated and can be ruled out with electrical these potentials originate in muscle tissue. 216 Single-fiber
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 277
J200,.V
Iliopsoas
brachii
IOms
Figure 7·17. Three examples (A-C) of complex repetitive dis Additional fibers excited before the principal pacemaker is re
charges. Note how the same potentials appear in the same repetitive activated form the remaining spike potentials of the CRD. A
groups. The minor differences between discharges is due to baseline
irregularities.
CRD, therefore, consists of serially activated single muscle
fibers that fire in the same pattern time after time. The CRD
continues to fire until either the principal or co-pacemaker alters
electromyography jitter variability between the individual spike the intra/extracellular ionic ratios sufficiently to block further
potentials is usually less than 5 ~S.225 When jitter values of such action potential generation, at which time abrupt cessation of
low magnitude are found, neuromuscular transmission is not in firing occurs. It is also conceivable that a discharge from an
volved in the generation of these potentials. It is postulated that other impUlse-generating site blocks the pacemaker's action po
cross-talk or ephaptic conduction between neighboring single tential through a loop collision.
muscle fibers forms the basis of the observed repetitive firing Complex repetitive discharges may be seen in a variety of
pattern. The proposed mechanism of CRD generation is as fol mostly longstanding diseases and often accompany fibrillating
lows (Fig. 7-18): (1) The action potential of a spontaneously fib potentials (Table 7-10). These potentials have been observed in
rillating single muscle fiber, principal pacemaker, ephaptically myopathies such as polymyositis and various forms of muscular
activates one or several adjacent muscle fibers at a low thresh dystrophy.92.220 There have also been reports of finding CRDs in
old region on their membranous surface; (2) One of these adja chronic denervation states such as motor neuron disease, radicu
cent muscle fibers re-activates the principal pacemaker, causing lopathies, and polyneuropathies.92
it to fire slightly earlier than it would because of its inherent fib
rillating rate. The muscle fiber that reactivates the principal Myotonic Discharge
pacemaker is called the co-pacemaker and forms a closed loop The phenomenon of delayed muscle relaxation following muscle
representing the cycle time or repetition rate of the CRD; (3) contraction is referred to as myotonia or action myotonia. 193.219
Fasciculation waveform morphology has the same characteris with these potentials is a type of sputtering often heard with a
tics as that of simple motor unit or polyphasic action potentials low-powered motor boat engine. The actual discharge may be
with respect to amplitude, duration, and phases (Fig. 7-20).227 distinguished from CROs in that myokymic discharges do not
Their discharge rate (l Hz to many per minute) is irregular and display a regular pattern of spikes from one burst to the next,
not under voluntary control; nor are they influenced by mild con nor do they typically start and stop abruptly. Physiologically,
traction of the agonist or antagonist muscles (Table 7-13). The myokymic discharges are groups of motor units, while CRDs
site of origin of fasciculation potentials remains unclear, although are groups of single muscle fibers.21o The groups of motor units
it appears that the spontaneous discharge may arise from within within a burst may fire only once or possibly several times.
the spinal cord (anterior hom cell),195 along the entire peripheral Also, the sputtering bursts of myokyrnic discharges sound quite
nerve (particularly the terminal portion),149 or at times within the different from the continuous drone of a CRD.
muscle itself.2JO Anterior horn cell, peripheral nerve, or terminal The documentation of myokymic discharges can be found in
nerve membrane variations in ex.citability have been suggested as normal individuals where the orbicularis oculi may twitch for
possible causes for the spontaneous motor unit discharges. The days.3 Myokymic discharges may appear in several patterns: 3.62
majority of fasciculation potentials observed in normal individu focal (one muscle), segmental, or generalized. Focal myokymic
als occur in the foot intrinsic muscles or gastroc-soleus muscle. l66 potentials can be observed exclusively in the face (facial myo
One may detect fasciculation potentials in a variety of dis kymia) arising from: fatigue, multiple sclerosis or a brainstem
eases as well as in normal individuals, particularly following neoplasm (Table 7-14). Segmental myokymic discharges can be
tension or anxiety, fatigue, heavy ex.ercise, coffee, smoking, or noted in syringomyelia or radiculopathies. Finally, generalized
no known associated factors (Table 7_13).67.68.166.190 Typical dis myokymic discharges have been detected in uremia, thyrotoxi
eases in which fasciculation potentials may be found include: cosis, inflammatory polyradiculoneuropathy and rare hereditary
motor neuron disorders, radiculopathies, entrapment neu disorders such as familial paroxysmal kinesigenic ataxia.23
ropathies, or cervical spondylotic myelopathy. Fasciculation po Limb myokymic discharges have also been described associated
tentials have also been described in metabolic disturbances primarily with radiation plexopathy. 3 The site of origin of the
including: tetany, thyrotoxicosis, and anticholinesterase over myokymic discharge remains unknown but has been postulated
doses. 21 Studies have attempted to distinguish between benign to arise anywhere along the motor neuron from the cell body to
and pathological fasciculation potentials. 118.146.227 To date, there the terminal axon. One theory suggests that transaxonal ephap
is no reliable way to categorize whether fasciculation potentials tic activation of neighboring axons results in the characteristic
herald a disease state by solely considering their inherent char discharges seen in myokymia,189
acteristics based on routine needle electromyography. Fascic
ulations with increased jitter and/or blocking (failure of Table 7-11. Characteristics of Fasciculation Potentials l54
neuromuscular junction transmission) on single-fiber elec
tromyography may, however, be considered abnormal. The best Appearance: Variable: normal or complex MUAPs
way to evaluate fasciculation potentials is to also analyze the Rhythm: Irregular
"company they keep." That is, a careful analysis of voluntary Frequency: 0.1 to 10 Hz
motor unit action potential morphology combined with a search Amplitude: > 300 IJV
for abnormal spontaneous potentials is required prior to con Stability: Stable
cluding that fasciculation potentials are an abnormal finding.
Observed in: a. Normal individuals
Spontaneous
MYOKYMIC DISCHARGE Following exercise
b. Lower motor neuron disorders
A readily observable vermicular (bag of live worms) or con
Amyotrophic lateral sclerosis
tinuous rippling movement of the skin, myokymia, is usually
Creutzfeldt-Jakob disease
associated with myokymic discharges. 3,62 A myokymic dis
Radiculopathy
charge is recorded when a needle recording electrode is placed
Peripheral neuropathy
into a muscle with the above noted finding. Bursts of normal ap
Entrapment neuropathy
pearing motor units with interburst intervals of silence firing at
c. Metabolic disorders
0.1-10 Hz in a semirhythmic pattern form the basis of a myo
Thyrotoxicosis
kymic discharge (Fig, 7-21; Table 7-14). Two to ten potentials
Tetany
within a single burst may fire at 20-150 Hz.62 These potentials
Anticholinesterase medication
are not affected by voluntary contraction. The sound associated
280 - PART II BASIC AND ADVANCED TECHNIQUES
I
II t tt II I t _ nIi. ~I 11111111
tI
----W~
r,!1 ,!
I ~ I ji UHH
Figure 7-21. Multiple examples of myokymic poten
tials from patients with radiation plexopathy. Note how
each burst of motor units is relatively regular, but the
MUAP content of each burst is variable. (From Albers JW,
HlIH~H~HHH ~I ~4 » HI
Allen AA. Bastron JD. et al: limb myokymia. Muscle Nerve
1981 ;4:494-504, with permission.)
--
--1 1 .'1
Multiple sclerosis
--UJ.lJ.WJ.IlUJIIIIUw\l!IWV.!.!~1 \,~(,J.... ~¥hll W""", '1.4 ... ,I" L~"'. ojo, I I I~ ~ 1,,4
Brainstem neoplasm
Normal lOOms
b. Extremity
Radiation plexopathy Figure 7-22. Neuromyotonic discharges. Recording of MUAPs
Chronic nerve compression from a patient with Isaacs syndrome. The continuous MUAP firing
Carpal tunnel syndrome eventually declines in number and amplitude as the muscle becomes
Radiculopathy exhausted. (From Daube JA: AAEM Minimonograph No. II: Needle
Examination in Electromyography. Rochester, MN, American Asso
Rattlesnake venom
ciation of Electrodiagnostic Medicine, 1979, with permission.)
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 281
CRAMPS
Cramps are sustained and possibly painful muscle contrac
tions of multiple motor units lasting seconds or minutes that
may appear in normal individuals or specific disease states (Fig.
7-23). In healthy subjects, a cramp usually occurs in the calf
muscles or other lower limb muscles following exercise, abnor
mal positioning, or maintaining a fixed position for a prolonged
period of time. 148 Cramps may also be induced by hypona Figure 7-23. Muscle cramp with MUAP frequencies between 30
tremia, hypocalcemia, vitamin deficiency, or ischemia. 67 One and 50 Hz. (From Daube JA: AAEM Minimonograph No. II: Needle
may also note the occurrence of cramps in early motor neuron Examination in Electromyography. Rochester, MN, American Asso
ciation of Electrodiagnostic Medicine. 1979, with permission.)
disease and peripheral neuropathies. Familial syndromes in
volving fasciculations and cramps; alopecia, diarrhea, and
cramps;198 and simply autosomal dominantly inherited cramps MUSCLE GENERATORS OF ABNORMAL
have been described. ISO VOLUNTARY ACTIVITY
A needle recording electrode placed into a cramping muscle
will reveal multiple motor units firing synchronously between NEURAL LOSS
40 and 60 Hz and occasionally reaching 200-300 Hz. 172 A large
portion of the muscle is simultaneously involved in a cramp as Motor Unit
opposed to the asynchronous excitation of motor units during If a muscle is completely denervated by a lesion affecting the
voluntary activation. Cramps are believed to arise from a pe motor neurons or the peripheral nerve, there will be a complete
ripheral portion of the motor unit. A cramp accompanied by absence of MUAPs. Fibrillation potentials and PSWs will appear
electrical silence is a pathological contracture as seen in Mc in great abundance following an appropriate period of time. A
Ardle's disease. '48 partial nerve lesion, however, may result in profuse fibrillations
and PSWs, with preservation of some MUAPs. A muscle that is
MUL:TIPLET DISCHARGES totally denervated can be reinnervated only by regrowth of the
peripheral nerve along its original course. A partially denervated
A clinical syndrome manifested by spontaneous muscle muscle will consist of denervated motor units and intact motor
twitching, cramps and carpo-pedal spasm is known as tetany. units. The motor units deprived of their innervation may be rein
This entity usually results from peripheral andlor central nervous nervated by one of two mechanisms. The first process involves
system irritability associated with systemic alkalosis, hypocal a regrowth ofaxons along the previous neural pathways. I IS
cemia, hyperkalemia, hypomagnesemia, or local ischemia.139 Neural regrowth occurs at approximately 3-4 mm per day.9.98
Clinically one may induce tetany by tapping the facial nerve The second manner in which denervated muscle fibers can be
(Chvostek's sign), the peroneal nerve at the fibular head (per reinnervated is through collateral sprouting. 238 That is, terminal
oneal sign), and inducing limb ischemia (Trousseau's sign).'08 axons from intact neighboring motor units sprout additional ter
In the above conditions, characteristic motor unit potentials minal axons at their branch point nodes of Ranvier. Denervated
may be observed. A single motor unit potential may fire rather muscle fibers somehow direct the growth of new terminal
rapidly with an interdischarge interval of 2-20 ms twice (dou sprouts through the remaining Schwann cell sheaths (bands of
blets) or three times (triplets) or more (multiplets) (Fig. 7_24).133,210 Bunger) resulting in muscle reinnervation.s3 The motor unit ar
These potentials can be seen following voluntary contraction or chitecture of the muscle is permanently and irreversibly altered
be observed spontaneously from induction maneuvers noted in this manner and present during the rest of this person's life.
above in which MUAPs may fire in long trains or short bursts of
5-30 Hz (tetany). As opposed to doublets and triplets, paired
discharges have an interspike interval of 20-80 ms and can arise
in similar states as previously described.
TREMOR
Involuntary activation of multiple motor units arising from
the central nervous system in a semirhytbmic pattern is called a
tremor. The individual motor units within a tremor burst do not
possess a consistent relationship of firing from one burst to the
next. The electrical activity produced from a tremor complex,
therefore, continuously changes with respect to the motor unit Figure 7-24. Doublet (top trace) and multiplets (bottom trace)
morphology contained in successive firings. 61 ,133 The sponta MUAPs resulting from voluntary contraction. (From Daube JA:AAEM
neous activity associated with a tremor may render a search for Minimonography No. I I; Needle Examination in Electromyography.
subtle abnormalities of fibrillations and positive sharp waves Rochester. MN.American Association of Electrodiagnostic Medicine,
extremely difficult. 1979. with permission.)
282 - PART II BASIC AND ADVANCED TECHNIQUES
MUAP arises from just a few single muscle fibers less than 500
11m from the needle electrode. Why should a total reduction in
the number of muscle fibers, therefore, result in a decreased
MUAP amplitude? The answer to this question has not been
fully explained but may be partially addressed. It is possible that
the spike of the motor unit does have some contribution from all
or some portion of the muscle fibers in the motor unit. This
would explain why a random loss of muscle fibers could pro
duce a small reduction in the MUAP amplitude. The histologic
finding of fiber size variation may also play some role in MUAP
amplitude. A smaller muscle fiber could be expected to generate
less voltage upon depolarization, producing a smaller MUAP ~2mv
spike. Depending upon the size of the fiber nearest the record 200 ....
ing electrode, which is the primary influence upon MUAP am
plitude, one could anticipate both normal and abnormally small Figure 7-27. MUAP variability. A,An MUAP is recorded from a
MUAPs. As the severity of the disease progresses, an increased healthy individual. Note the identical appearance of the MUAP with
number of smaller diameter fibers may occur, enlarging the per each successive discharge. B,The same MUAP recorded from a person
centage of small MUAPs. Finally, an increase in electrically with Lambert-Eaton syndrome. Note the MUAP's highly variable mag
measured fiber density can arise because of some physical col nitude with each successive discharge.
lapse of the motor unit following muscle fiber atrophy or loss,
fiber spitting, and reinnervation secondary to segmental necro total voltage associated with the observed MUAP. A slightly dif
sis. It is also possible to see normal or even large amplitude ferent voltage for each sequential MUAP firing means that the
MUAPs. Locating the needle electrode tip immediately adjacent MUAP's amplitude will vary somewhat with each discharge,
to a hypertrophic muscle fiber may result in a relatively large thereby generating the so-called MUAP variability (Fig. 7-27).
MUAPspike. This situation is completely different for the normal motor unit,
A needle recording electrode placed in a muscle affected by a which has the same appearance with each successive discharge.
myopathic disease can show all of the above noted possibilities.
Small amplitude and short duration MUAPs with an increase in ABNORMAL MUAP RECRUITMENT
the number of phases accompanied by satellite potentials have
all been documented. Most myopathies reveal both normal and Following alteration of the motor unit secondary to pathol
short duration MUAPs where the number of short duration ogy, one can expect to note abnormalities in MUAP recruit
MUAPs increase with disease progression. 34•37•40 The special ment. Distinct recruitment patterns may be observed depending
technique of single-fiber EMG has demonstrated an increase in upon the type of disorder or which portion of the motor unit is
muscle fiber density.17l Of course, the segmental necrosis could affected. Two major abnormal recruitment patterns may be de
lead to the observation of fibrillation potentials and positive sharp tected. If a lesion damages the neural portion of the motor unit,
waves. 69•70 The designations "myopathic potentials" and "brief a so-called "neurogenic recruitment" may be observed depend
small abundant polyphasic potentials" (BSAPPs) have been dis ing upon how many motor units are injured. On the other hand,
couraged in favor of more descriptive MUAP terminology re a random loss of muscle tissue (myopathy) can result in a "my
garding MUAP morphologic characteristics. This is because opathic recruitment" pattern. Although the sensitivity of recruit
MUAPs are not pathognomonic of any disease in particular, but ment patterns in various disease states is most likely less than
more accurately describe possible disease processes in general. quantifying MUAP duration,72.ls3 discussion regarding potential
findings is useful in understanding how different lesions can
MUAP Findings in Neuromuscular generate distinct recruitment findings.
Junction Disorders
There are three anatomic regions of the neuromuscular junc Neurogenic Recruitment
tion that can be considered primary areas where a disorder may If the motoneuron's neural elements (anterior hom cell, pe
occur: (1) presynaptic terminal (e.g., botulism, Lamber-Eaton ripheral nerve, terminal axons, and presynaptic aspect of the
syndrome), (2) synaptic space (e.g., organophosphate poisons, neuromuscular junction) are permanently affected by disease
congenital disorders), and (3) postsynaptic membrane (e.g., and Wallerian degeneration occurs, then all of the muscle fibers
medication, myathenia gravis). Diseases affecting the first and innervated by those injured axons will be denervated. As previ
second anatomic regions are more likely to be encountered clin ously noted, collateral sprouting will reinnervate these muscle
ically and can give rise to a particular kind of MUAP abnormal fibers comparably increasing the number of muscle fibers be
ity, i.e., motor unit variability similar to that previously longing to one motor unit. 29.238 When the patient calls upon the
described for the newly reinnervated MUAP. Normally, all of neuromuscular system to function, the interplay between the
the muscle fibers comprising a single motor unit all depolarize central nervous system and peripheral nerve-muscle compo
and summate their individual electrical signals to generate an nents through the "servo-control" mechanism of the muscle
MUAP with the same configuration and magnitude from one spindles is inextricably altered. In effect, there are fewer motor
discharge to the next. In diseased or immature neuromuscular units available with larger complements of muscle fibers com
junctions, failure of several individual muscle fibers comprising pared to the previous normal situation. The manner in which the
a motor unit to discharge with each firing of the anterior horn electrodiagnostic medicine evaluation recognizes this altered
cell results in a slightly different number of muscle fibers elec state is through observing the MUAP recruitment pattern.
trically active at any particular time for that motor unit. As We must assume that the damage inflicted upon the moto
result, each time the anterior horn cell fires, there is a different neuron is severe enough to compromise a sufficient number of
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 285
motor units to display an abnonnality in motor unit recruitment. Table 7·15. Neurogenic Recruitment
The exact number of motor units necessary to meet this assump Motor Unit Recruited
tion is unknown. For discussion purposes, let us suppose that in 1st (A) 2nd (B) 3rd (C) 4th (D)
our 4 motor unit example under "MUAP Recruitment (Nonnal
Muscle);' motor units B and C are no longer present (Table 7-15). A (20 Hz)
Placing a needle recording electrode into the affected portion of A (25 Hz) 0 0
muscle will demonstrate a characteristic recruitment order for a A (30 Hz) 0 0 0(20 Hz)
minimal muscle contraction. Initially, motor unit A will begin Motor unit A begins firing at 20 Hz because motor units Band C are not pre
firing at about 20 Hz and increase its firing frequency with an sent.When motor unit A fires at 30 Hz, motor unit 0 finally becomes active at
increase in muscular effort.12•183 Nonnally, when motor unit A 20 Hz. The recruitment pattern is altered. and fewer motor units are firing at
reaches 10Hz, a second motor unit, i.e., motor unit B should higher than anticipated rates.
begin firing. In this instance, however, motor unit B, is absent
because of disease, and motor unit A has already proceeded to a lesions, the number of motor units are unaffected, but the
rapid firing frequency to generate the force requested. The force muscle fiber content of each motor unit is reduced. [n essence,
required by the individual must be met by the only physiologic the net force output from each motor unit is diminished com
mechanism remaining, which is an increase in motor unit A's pared to normal. The manner in which the central-peripheral in
firing rate. The first motor unit increases it firing rate still fur teraction compensates for this situation is for multiple motor
ther approaching 25 Hz. Note that at 20 Hz, the recruitment units to begin firing simultaneously at high rates. This may be
ratio predicts that 4 motor units should be present. Under better understood if we return to our simple motor unit example.
nonnal conditions, when motor unit A reaches about 15 Hz, If the patient is requested to minimally contract a muscle af
motor unit C should have become activated. Unfortunately, fected by a myopathic process, the initial force output for the first
motor unit C is also affected by a disease process and cannot recruited motor unit is less than nonnally anticipated. Motor unit
fire. At this point, the recruitment ratio states that 3 motor units A flring at 5 Hz produces insufficient force to satisfy that desired
should be present (15 Hzl5 =3 motor units). As the patient tries by the patient. As a result, additional motor units..are immediately
to produce still more force, motor unit A eventually reaches 30 added so they may contribute their muscle fibers to the net force
Hz, and motor unit D now fires. It also begins firing at an in output. The result is 5 separate motor units (Table 7-16) for exam
creased rate of 20 Hz to meet the force demanded of the muscle. ple, firing at relatively high rates (15 Hz).11.183Jt is difficult for the
We now have two separate motor units firing and the recruit patient to recruit only one motor unit. The motor unit ratio states
ment frequency is 30 Hz. That is, the firing rate of the first that three motor units should be present only if the first recruited
motor unit when the second motor unit became active is 30 Hz. motor unit is firing at 15 Hz. [n our example, however, we have 5
There are a decreased number of motor units active for the fre motor units firing at 15 Hz. The final observation on the CRT
quency of the first motor unit's firing rate. This is the so-called screen is that there are too many, or an increased number of,
neurogenic recruitment pattern also referred to as "decreased motor units firing for the amount of contraction requested, i.e.,
recruitment" or "reduced recruitment." A recruitment ratio of IS motor units B-E fire earlier than nonnalleading to the tenns
(30/2 = 15) is noted in this example and is clearly abnonnal as it "early or increased recruitment." This process differs from the
is significantly greater than 5. The loss of motor units may be so "neurogenic" scenario in that additional motor units with fewer
profound in some motor neuron or peripheral nerve disorders muscle fibers per motor unit are called upon for their contribution
that muscle activation results in only one motor unit firing at to the net force output. Because the motor units contain fewer
30-40 Hz. muscle fibers and produce less force than normal, the only strat
A decreased number of motor units firing at abnonnally high egy left is to have them fire both earlier and at faster rates. In our
frequencies may also be seen in the presence of nonnal motor example, a firing rate of 15 Hz for 5 motor units results in a re
units whose neural conduction may be temporarily blocked. A cruitment ratio of 3, which is less than a nonnal ratio of 5.
potentially reversible conduction block along a nerve, neu Myopathic processes, therefore, yield recruitment ratio values
rapraxia, may occur secondary to trauma, ischemia, and other less than 5 while neurogenic diseases generate recruitment ratio
conditions. Neurapraxia may also coexist with axonal loss, values greater than 5. Of course, 5 is a rough guide and some vari
yielding a mixed lesion. A rather "pure" fonn of neurapraxia is ability (e.g., greater than 3 but less than 8) may be nonna!. This is
the common experience when a "foot goes to sleep" after the observed electrically as a rapid obliteration of the baseline sec
crossing of legs for prolonged periods. The peroneal nerve fails ondary to mulitple MUAPs being activated with just a slight in
to conduct efferent motor and afferent sensory impulses for the crease in attempted force production.
time necessary to reverse the ischemic block of neural impulses. It must be emphasized that the above description of motor unit
For the time of conduction failure, however, a number of motor recruitment is an oversimplification for illustrative purposes and
units are rendered nonfunctional. The muscle is effectively de most likely does not accurately reflect the complexities of the in
prived of multiple motor units. A recruitment pattern under con teraction between the central nervous and peripheral neuromus
ditions of neurapraxia is very similar to that seen in actual cular systems. The observations noted above can be practically
motor unit loss, i.e., decreased numbers of MUAPs firing at in
creased rates. The recruitment pattern then returns to nonnal Table 7·16. Myopathic Recruitment
when all of the nerve fibers are capable of conducting electrical Motor Unit Recruited
Myogenic Recruitment A <IS Hz) B (15 Hz) C (IS Hz) 0(15 Hz) E (IS Hz)
The random loss of muscle fibers in diseases such as poly A random loss of muscle fibers results in each motor unit containing a smaller
myositis or various muscular dystrophies will also yield charac complement of muscle fibers. For a given force output. therefore. more individ
teristic recruitment patterns. Unlike the above "neurogenic" ual motor units must fire earlier and faster than normal.
286 - PART II BASIC AND ADVANCED TECHNIQUES
applied to the first few recruited motor units to arrive at some from intramuscular pain receptors l65 and subjective patient fac
insight regarding possible lesions affecting the motor unit. The tors.103.132.206 Some of these factors impacting upon the patient's
sensitivity of motor unit recruitment analysis is unknown and view of the examination include: warnings about the test from
most likely does not precede changes in MUAP duration for as well-meaning friends or poorly informed medical personnel,
sessing pathology of the motor unit. fear of needles, sound emanating from the instrument's speaker,
fear of an unfamiliar test, etc. 206 Studies attempting to examine
RECRUITMENT IN STROKE some of these factors demonstrated that a patient's anxiety
level, perception of his or her own pain, and female gender were
There are few data examining in detail the differences in predictors of individuals who experience the most pain during
MUAP recruitment between healthy persons and those sustain an examination. IOJ,132 Although the number of examination sites,
ing a stroke. The little information present suggests that the patient's age, length of examination or wait, day of week, previ
motor units begin to fire at a lower rate (7 Hz vs. 8 Hz) in the ous examination, or time of day does not appear to adversely
hemiplegic limb, while the second recruited motor unit begins affect pain perception, several body areas were found to be
firing earlier (10Hz vs. 15 Hz) than anticipated, given the first more uncomfortable than others. Specifically, cervical
motor unit's firing rate. 99 These findings are more pronounced paraspinals were the most painful region of the body examined
in distal compared to proximal limb muscles. In all muscle followed by the lumbosacral paraspinal muscles and the hand
groups on the affected side, a diminished degree of voluntary intrinsic muscles.200
control is found, as would be anticipated. Although the examiner cannot change the individual's per
ception of pain, it may be advisable to attempt to reduce the
ADDITIONAL WAVEFORMS anxiety level. The use of analgesics has been recommended;143
however, we do not use medication during the electrodiagnostic
Three additional waveforms that may be observed during the medicine consultation. Audio analgesia in the form of music or
needle electromyographic examination are discussed. It is white noise played through headphones may be of some assis
relatively common to observed a sinusoidal wave representing tance in reducing the patient's perception ofpain.206 As has been
60 Hz interference in the U.S. and 50 Hz interference in other previously noted, information delivered in a calming and reas
parts of the world. Detection of this waveform usually means suring voice might help some persons through the consultation.
there is less than optimal impedance matching between the elec It is the belief of these authors and others 201 that monopolar nee
trodes or even an open circuit. When this waveform is recorded, dles cause less pain than standard concentric needle electrodes
all electrodes must be checked to ensure that none have de probably because Teflon reduces the needle shaft's drag on the
tached from the patient and that there is adequate electrode tissue.
paste between the electrodes and the patient. Also, a broken
wire may be present beneath the plastic coating of the elec CONTRAINDICATIONS AND COMPLICATIONS
trodes. After these obvious sources have been checked, the in RELATED TO NEEDLE EXAMINATION
strument's preamplifier should be positioned close to the patient
and away from the instrument or other potential sources of in In the authors' opinion there are no absolute contraindica
terference (monitors, printers, medical equipment, etc.). Placing tions to performing a well-directed and selective needle elec
an ungloved hand on the patient can help reduce this type of in tromyographic examination. A relative contraindication to
terference. Additional sources of interference are discussed in inserting electromyographic needles into muscle tissue is most
the chapter dealing with instrumentation. assuredly persons who have a coagulopathy either medically in
When recording with a needle electrode at essentially any loca duced or otherwise acquired. 4•48 It is certainly possible for indi
tion on the patient's torso, a regular occurring waveform that is viduals on a sufficient dosage of sodium warfarin (Coumadin)
relatively silent may be observed. Slowing the instrument's to bleed significantly following a needle study. The propensity
sweep speed will reveal that the fIring rate of this potential is about to bleed excessively following needle electromyography is in
1 Hz, i.e., the waveform is the patient's EKG. This waveform can creased in patients with a platelet count below 50,OOO/mm 3 , a
be particularly prominent when recording from the chest or back prothrombin time 1.5-2 times control values, and intravenous
when examining the shoulder rotators or the serratus anterior mus heparin with a concomitant partial thromboplastin time above
cles. A related waveform with a similar firing rate but of larger 1.5-2 times the controllevel. 4 In these patients, the referring
magnitude results when a patient has a pacemaker. This wave physician and electrodiagnostic consultant must weigh the risk
form typically has a loud high-pitched sound associated with it. benefit ratio of examining the patient with needle electrodes.
Should a study be deemed necessary, a limited number of elec
trode insertions should be performed in a well-selected popula
NEEDLE ELECTROMYOGRAPHY: tion of muscles to yield the greatest amount of information with
RELEVANT ISSUES the least number of needle punctures. It is also prudent to apply
localized pressure to the puncture site following needle re
PAIN ON NEEDLE EXAMINATION moval. A needle examination in hemophiliacs should be de
ferred unless their clotting factors are optimized.
Unfortunately the electrodiagnostic medicine consultation There may be some hesitancy in performing a needle exami
can be an uncomfortable experience for the patient. The pain nation on a limb with significant lymphedema because of an in
perceived during a study can limit the investigation and the creased risk of infection. Again, the risk-henefit ratio must be
amount of information gained. Pain perception does not solely consider prior to engaging in a needle investigation. In the au
arise from the insertion of a needle electrode. To be sure, punc thors' opinion, one should proceed with caution in such patients
turing the skin and particularly the superficial fascia accounts and perform only a limited number of needle insertions after thor
for most of the examiner-delivered pain with some contribution oughly preparing the skin insertion site with an iodine solution.
Chapter 7 NEEDLE ELECTROMYOGRAPHY - 287
Soft tissue infections secondary to needle electromyography having Jakob-Creutzfeldt disease or other disorders suspected
have been reported but are rare. Five cases of a nontuberculous of being tranmitted through slow viruses should be discarded
mycobacteria (Mycobacteriumfortuitum) were postulated to following autoclaving for 1-1.5 hours at 120°C at 20 pounds
have been the result of a needle electromyographic examination per square inch.l0l.l60 It is the authors' personal preference to use
performed by a single individual. 170 Although the sterilization disposable needle electrodes on all patients receiving a routine
procedures for the nondisposable needle were adequate, the electrodiagnostic medicine consultation. This allows one the
report appeared to implicate the needle examination as the cul ability to inform the patient that the needle about to be inserted
prit for the infections. Some electrodiagnostic medicine practi is sterile, never been used before, and will be discarded once the
tioners clean the needle insertion sites with alcohol prior to examination is completed. Most persons appreciate this consid
inserting the needle electrode. The value of this practice is ques eration. Standard concentric and monopolar needle electrodes
tionable if the intent is to sterilize the skin and may result in are now manufactured with sufficient quality control to provide
more pain upon needle insertion if the alcohol is driven into the high quality electrodes for acquiring routine data, obviating the
subcutaneous tissues when not allowed to dry. need to use nondisposable needle electrodes. Unfortunately, this
It is certainly a good practice for practitioners to employ the cannot be said of special needle electrodes such as single-fiber
use of nonsterilized gloves to protect themselves from blood and macro EMG needles, which require sterilization procedures
products and blood borne pathogens contaminating their hands as they are rather expensive to discard after one use. Most rou
following withdrawal of the needle electrode. 50.51 Once the tine sterilization procedures used in hospital settings are suffi
gloves have been used, they should be appropriately discarded. cient to destroy bloodborne pathogens including the HIV virus
It is inappropriate to wash or otherwise attempt to disinfect the and can be used for such needles with the exception noted
gloves as this may cause undetected disintegration of their in above. 5o,51 Solutions of sodium hypochlorite (household bleach)
tegrity. Use of gloves is an inconvenience as the "feel" of the in dilutions of 1: 100 to 1: 10 have been deemed effective as a
needle electrode penetrating various tissue planes or encounter germicide.
ing fibrous tissue is dulled, not to mention decreased manual The electrodiagnostic medicine practitioner is certainly at
dexterity and adhesive tape sticking to the gloves. Given all of risk for needle punctures. This is likely to occur when attempt
the preceding reasons not to use gloves, one can accommodate ing to resheathe the needle electrode either between insertions
the sensation of performing a needle examination with gloves. or when the examination is complete. 60 A good practice is to
In any event, even though the risk of human immunodificiency have some type of simple mechanical device capable of holding
virus (HIV) after skin contact with infected blood is less than the needle's protective covering so that the practitioner does not
the 0.5% for needle puncture exposure,50,51 one should never have to hold this covering and risk a self-inflicted puncture. A
apply pressure to a bleeding needle site with unprotected skin. It large sterile foam block may also serve this purpose as one can
is also good practice to wash one's hands with an appropriate readily impale the needle into the foam and move it to the next
disinfectant soap prior to and following a needle examination. needle location. Following completion of the needle study, the
Various complications have been documented to result from needle and foam block can be discarded.
the needle electromyographic examination. Urticaria changing
into vitiligo has been reported in a hysterical individual. 229 More MUSCLE BIOPSY/SERUM CK LEVEL
serious complications have been the production of pneumotho
races following needle studies. Reports document that it is pos Inserting a hypodermic needle or electromyographic needle
sible to induce a pneumothorax after inserting a needle recording electrode into muscle tissue results in fiber damage or
electrode too far superiorly above the scapular margin when at so-called "needle myopathy."94 In both humans and animals,
tempting to examine the supraspinatus muscle. 191 Placing the placing a needle electrode into various muscles produced intra
needle too far laterally from the midline when investigating cer muscular evidence of muscle fiber destruction. Muscle biopsies
vical paraspinal muscles can also penetrate the pleural performed parallel to the plane of needle insertion site revealed
cavity.122.123 Concern has also been expressed about serratus an evidence of muscle fiber necrosis within 1-24 hours and phago
terior (possible pneumothorax) and abdominal muscle (peri cytosis at these regions within 1-3 days. After 3 days biopsy
toneal cavity insertion) needle examination as well as specimens demonstrated large nuclei with prominent nucleoli
diaphragmatic investigation. 4 It is recommended that one should and accompanying basophilic cytoplasm suggesting muscle
stay rather close to the midline when studying paraspinal mus fiber regeneration. A biopsy specimen taken perpendicular to
cles, particularly in the cervical region, and place the needle the plane of the needle's tract would reveal well-localized
toward the medial border of the scapula for the supraspinatus region of muscle destruction and phagocytosis. This appearance
muscle. The authors suggest that when examining any muscle, may be mistaken for inherent muscle disease and lead to an er
particularly those prone to result in adverse consequences, the roneous diagnostic conclusion. It is recommended that muscle
amplifier should be activated immediately upon entering the biopsies not be performed on muscle irrespective of their clini
subcutaneous tissue. Once insertional activity is detected, the cal involvement if an electromyographic examination has been
plane of exploration should be altered to avoid any potentially carried out. The biopsy should instead be taken from a similarly
hazardous structures. If insertional activity disappears during involved muscle not studied with a needle electrode.
the examination, the needle should be withdrawn toward the If the patient is to undergo an electrodiagnostic medicine ex
surface and carefully repositioned. amination prior to receiving a muscle biopsy, only one side of
the body should be investigated. The practitioner should then
STERILIZATION OF NEEDLE ELECTRODES clearly state what muscles were examined on which side of the
body and communicate that these limbs should not be used for
Although there are guidelines for properly sterilizing reusable muscle biopsy. On the other hand, if a needle examination is
needle electrodes through steam autoclaving, those needles performed following a muscle biopsy, the needle should not be
known or suspected to have come in contact with patients located in muscle tissue surrounding the biopsy site. Membrane
288 - PART II BASIC AND ADVANCED TECHNIQUES
instability can be detected in muscle tissue separated from its X. Barchi RL; A mechanistic approach to the myotonic syndromes. Muscle r\erve
I 982;5:S60-S63.
nerve supply as a result of the muscle biopsy. 178 9. Berenberg RA, Forman DS. Wood OK, et al: Recovery of peripheral nerve
As previously stated, needle insertion causes rather obvious function after axonotomy. Effect of triiodothyronine. Exp Neurol 1977;57:
muscle fiber disruption on microscopic examination. It is rea 349-363
sonable to conclude that interrupting the muscle membrane 10. Bolton CF. Sawa GM. Carter K: The effects of temperalUre on human com
pound action potentials. J Neurol Neurosurg Psychiatry 1981;44:407-413.
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leased from various body tissues of which the highest content is 12. Brandstater ME. Lambert EH: Motor unit anatomy. Type and spatial arrange
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tion following an electromyographic examination could lead to 13. Brazier MAB: Electrical Activity of the Nervous System. London. Pitman
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14. Brodal A: Neurological Anatomy in Relation to Clinical Medicine. New York,
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portion of the electrodiagnostic medicine consultation are an 28. Buchthal F. Guld C, Rosenfalck P: Multielectrode study of the territory of a
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extension of the physical examination on a cellular level. It is 29. Buchthal F. Rosenfalck P: Rate of impulse conduction in denervated human
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Chapter 8
Quantitative EMG
CKAPTEIt ouTUIIE
The needle electromyographic (EMG) examination is a EMG examination to better identify and document signal abnor
powerful procedure in the diagnosis of nerve and muscle dis malities. The integration of QA and the routine examination
eases. Signals are recorded using a concentric needle or leads to "objective EMG."139 This approach helps not only to
monopolar needle electrode. The intramuscularly recorded detect abnonnalities, but in some instances to assess their sever
EMG wavefonn is assessed subjectively from its appearance on ity, status (active versus inactive), duration (acute versus
the display screen and its corresponding sound on an audio chronic) and perhaps prognosis. By practicing QA techniques,
monitor. In quantitative analysis (QA), a statistically valid one may train the eyes and ears to recognize subtle abnonnalities
sample of EMG signals is quantified manually or using auto that may otherwise be missed. Obviously, one cannot practice
mated computer-based methods. One can also use specialized every available QA technique. However, a basic understanding
electrodes to facilitate QA. Individual and mean wavefonn pa of these methods will allow the practitioner to better decide
rameter values are compared to appropriate reference values to when to order or perfonn a QA procedure and how to interpret
identify the underlying disease processes. When EMG abnor the results.
malities are obvious on the routine needle evaluation, QA may Finally, many QA techniques have recently become user
not add much to the electrodiagnostic medicine evaluation. In friendly and more automated. Additionally, the cost of instru
fact, QA is still perfonned infrequently in most clinical EMG ments that support such analyses has decreased dramatically.
settings. As a result, many electromyographers may consider The statistical treatment of data has also changed and become
QA as a specialty within the practice of EMG having little or no automatic for many applications. As a result, QA in one muscle
role in day-to-day clinical practice. In this chapter our goal is to may now require just a few minutes. This time saving gives the
dispel this "myth." practitioner an incentive to master these various techniques and
It is important to recognize that QA provides a foundation for implement them in routine EMG studies.
the routine needle EMG examination. All the criteria used in We begin by a brief description of the current concept of
signal assessment today are derived from QA studies per motor unit pathology, the routine EMG examination, and a
fonned, in some cases, up to 5 decades ago. In our experience, generic description of quantitative analysis. Next we review the
QA is particularly useful when the abnormalities on routine techniques of EMG quantification using the standard electrodes,
EMG are equivocal. QA techniques are essential when EMG is Le., eN or MN. This is limited to analysis of MUAPs and the IP
used serially to assess disease progression. The knowledge and signals. Subsequently we review techniques using special elec
techniques of QA can be easily incorporated into the subjective trodes such as single-fiber and macro EMG. We also review
293
294 - PART II BASIC AND ADVANCED TECHNIQUES
of endplates within a localized region of a muscle is referred to nerve APs from different fibers arrive at the presynaptic termi
as the endplate zone. At the arrival of a nerve AP, the nerve ter nal at different times. The time of neuromuscular transmis
minals release acetylcholine (ACh), which diffuses across the sion is quite small, but may vary among different fibers and
synaptic cleft and binds to the receptors on the postsynaptic changes from one discharge to the next in the same fiber. (Of
membrane. This depolarizes the membrane, producing the end note, this variability forms the basis for the jitter measured by
plate potential (EPP). When the EPP exceeds the muscle single-fiber EMG.) Once a muscle fiber AP is generated, its
membrane threshold level, it produces a muscle fiber AP, which propagation time to the electrode will vary due to differences in
propagates in both directions from the endplate towards the ten the propagation velocity. Large fibers conduct APs faster than
dons. The AP initiates a chain of events that leads to muscle smaller fibers. Finally, the endplates of different muscle fibers
fiber contraction. Thus, every time the motor neuron discharges, are scattered within a region of the muscle. Hence, action po
the muscle fibers in the MU respond by producing an electrical tentials from different muscle fibers must travel different dis
and a mechanical output. The MUAP is the summated electrical tances to reach the recording electrode (Fig. 8AA).
activity of an MU recorded by an EMG electrode (Fig. 8-4D). A needle EMG electrode records the summation of action po
The generation of the MUAP is shown schematically in Figure tentials from all muscle fibers in the MU, i.e., the MUAP (Fig.
8-4C, which demonstrates three imponant characteristics of the 8AD). The MUAP waveform depends not only on the position
muscle fiber potential within the MU. of the electrode in relation to the muscle fibers as described
The shape of the extracellularly recorded muscle fiber AP is above but also upon the MU architecture, i.e., the number,
biphasic or triphasic, which is quite different from the monopha size, muscle fiber distribution, and endplate distribution.
sic intracellular AP recording. 2 In extracellular recordings (Fig.
8-4C), a downward (i.e., positive) deflection is recorded when QUANTITATIVE ANALYSIS
the intracellular AP leaves the endplate and approaches the elec
trode. When the intracellular AP passes by the electrode, the Quantitative analysis may be divided into three general steps.
main positive-to-negative going spike of the extracellular AP is First the signals are acquired using standardized conditions.
generated. When the intracellular AP propagates away from the These include the size and placement of electrodes, filter set
electrode, the extracellular potential again deviates in the posi tings, and the method of signal acquisition and processing. In
tive direction and finally returns to the baseline, thus a triphasic the second step, one makes measurements of the recorded po
waveform is recorded. Clinical EMG recordings are made in the tential. This may be done manually or by using computer-based
extracellular space. In this chapter the term AP implies an extra algorithms. Manual measurements may require standardized
cellular recording unless specified otherwise. display settings such as the display gain. The computer-based
When the EMG electrode is in the endplate area, the initial measurements may use criteria that are not always known to the
positive deflection signifying AP propagation from endplate to user. Finally, one performs analysis of measurements by com
the electrode does not occur. The AP has an initial negative paring them with appropriate reference values.
(upward) deflection. An initial negative deflection is routinely We prefer to use the term reference limits instead of nonna.
observed in the compound muscle action potential (CMAP) limits for two reasons. First, the subjects recruited for develop
recordings made when the surface active electrode is placed ing the limits are not tested extensively to establish the lack of
over the endplate area of the tested muscle. any nerve or muscle disease. When one begins recordings, it is
The peak-to-peak amplitudes of APs vary considerably not uncommon to occasionally find "abnormal" EMG charac
among different fibers of the MU. This occurs due to different teristics by subjective assessments. This presents a dilemma for
distances between the active recording surface of the electrode accepting or rejecting this normal subject for the study. Second,
and the fibers of the MU (Fig. 8-4B). The electrode records a the reference values are often defined as including 90-95% of
large-amplitude AP from a fiber that is close to the recording all data recorded from the normal population. There is thus
surface (e.g., fiber #4 in Fig. 8-4). These APs are rich in high always a slight chance that a normal subject would have EMG
frequencies and have shon rise times. This gives them a high measurements outside the normal limits. Over the last five
pitched sound, often described as sharp or crisp, on the audio decades, two distinct strategies have been developed to assess
monitor. The AP of a distant muscle fiber has low amplitude QA measurements. In the first, 20 MUAPs are recorded from
(e.g., fiber #1 in Fig. 8-4). It also has a long rise time and mini different sites. The mean values of these measurements are used
mal high-frequency components, which gives APs from distant to assess abnormalities. This mean value represents the overall
fibers a "dull" sound on the audio monitor. The decline of the sampling of the tested muscle. In serial EMG studies, this
potential amplitude with radial distance depends upon the size allows one to assess changes in the MU due to disease progres
and shape of the recording electrode. In needle EMG, one may sion. However, it can be time-consuming to acquire the 20 or
use electrodes with small (single-fiber EMG), medium (concen more potentials required to compute the mean values. Using
tric or monopolar), or large (macro EMG) recording surfaces to fewer measurements may give a false high or low value of the
obtain different rates of amplitude decline, i.e., different selec mean. 61
tivity. These electrodes give complementary information about Analysis based on mean values is different from subjective
the MU, as described later in this chapter. assessment of EMG signals. In the routine EMG examination,
The peaks of individual muscle fiber APs of the MU occur at one can easily recognize potentials that are "obviously abnor
different times, indicating that they are not synchronous when mal," e.g., a giant CNEMG MUAP or blocking on single-fiber
they arrive at the recording electrode (Fig. 8-4C). The differ EMG recordings. This lead StAlberg and coworkers to develop
ence in their arrival time, called the temporal dispersion, re the outlier approach of assessment. 190.191 Instead of defining ref
sults from several physiologic factors. erence limits based on mean values, they defined the limits for
The nerve AP propagates through terminal branches of different individual potentials. A potential with measurements outside the
lengths (Fig. 8-4A). Funhermore, the AP propagation velocity reference limits is called an outlier. The limits are defined such
may vary among different terminal branches. As a result, the that all control subjects have fewer than 10% outlier potentials.
Chapter 8 QUANTITATIVE EMG - 297
When one aims to record up to 20 different potentials, a study The sweep setting is indicated in two different ways: sweep
would be abnormal when the third abnormal potential was duration or sweep speed. The two descriptions are related as
recorded. This could very well occur within the first few record follows:
ings. At this stage the quantitative procedure has reached diag
. _ Sweep duration (ms)
nostic significance and the test may be terminated. In this Sweep speed (ms/dlv) - Nurnber 0 fh'
onzon tal d'IVlSlOns
..
fashion, the time required for the test can be significantly re
duced. It is important to recognize that the reference limits for In Figure 8-5, the sweep duration is 100 ms. The 100 ms
the outlier approach are much wider than those used for mean sweep is divided into 10 horizontal divisions. This gives a
values. If one intends to follow the disease progression, how sweep speed of 10 ms/div. The duration of potential Dl in the
ever, 20 or more potentials must be acquired for analysis. top trace is roughly I division. Multiplying by the sweep speed
Both methods of analysis are used in quantitative analysis. It gives a value of 10 ms for the MUAP duration. The time inter
is important to recognize that reference values are affected by val between potentials D2 and D3 is measured as follows: After
technical factors (e.g., type of electrode, filter settings, tempera potential D2 on the third trace there are 9 divisions to the end of
ture), demographic factors (e.g., age, gender), as well as the trace. The signal continues on the fourth trace and the potential
nerve or muscle tested. One must match all of these factors D3 occurs after 1 division from left. Thus, potentials D2 and D3
before using published reference values. are separated by 10 divisions, i.e., 100 ms. When measured
more precisely using computer-aided cursors the interval was
Manual Measurements 105 ms; however, visual assessment is acceptably close to this
Quantitative analysis does not necessarily require automated value. Similarly, potentials Dl and D2 are separated by 12 divi
measurements. In fact, much of the earlier work on MUAP sions (1 on the first sweep, lOon the second and I on the third)
analysis and single-fiber EMG was performed by making or 120 ms.
manual measurements of EMG signal printouts. Although
modem instruments provide algorithms for automated analysis, MUAP Analysis
the automated measurements may not be accurate when the Measurements. Buchthal and his colleagues pioneered the
signal contains too much noise, interference, and artifacts. technique of MUAP analysis in the early 1950s by measuring
Hence one should be able to make visual assessments of time amplitude, duration, and phases (Fig. 8-6).25 The MUAP ampli
and amplitude measurements. In this chapter, the EMG signals tude is measured between the maximum negative and maxi
are shown in a raster fashion (Fig. 8-5). The signal display mum positive peaks. The MUAP onset occurs when the signal
begins with the top trace. The bottom trace is the latest-occur first deviates from the signal baseline as seen at a 100 J..lV/div
ring EMG signal. The five sweeps represent a 5OD-ms epoch of display setting. The MUAP end occurs when the waveform re
EMG for analysis and review. A grid superimposed on the dis turns and remains at the baseline. A phase represents a change
play divides the trace area in several divisions to facilitate sub in signal polarity about the baseline. A simple way of measuring
jective measurements. The display gain or sensitivity indicates
the amplitude change per vertical division. In Figure 8-5, the
Amplitude
peak-to-peak deflection of the potential on the top trace is about
T
2 divisions. MUltiplying by the gain of 100 INIdiv, the MUAP
* .--J100 ~V
amplitude is estimated to be 200 !lV.
5ms
A
01
· · . . . T
0-100 ms
· . . r
I
M I"
1-+1
-j
Spike Duration
MUAP Duration
.
100 - 200 ms
02 ,. .. .. . . . .. ..
~---- .. ----.-------------
200 - 300 ms """""'\
Y Linked Potentials
~3 ·
. /1\ B
300 -400 ms . .
400 - 500 ms r.
· · 100 ms
~O
T
m!-J 100.~V
1"'----.
... . .,MUAP Duration
.... J I Spike Duration
j,,_------+l
fjgure 8-6. MUAP measurements. Different measurements of
MUAP are illustrated using two different recorded MUAPs.ln A, turns
figure 8-5. Subjective EMG measurements. Five consecutive are indicated by T. Not all turns are identified. A questionable phase is
sweeps of the EMG signal are shown. The time of each sweep is indi indicated by #.An asterisk indicates a peak that does not qualify as a
cated on the left. Four discharges of a single MUAP are labeled 0 I, 02, tum. In B a polyphasic MUAP is seen, with many late components. The
03, and 04. See text for details. (slow wave) duration is shorter that the spike duration.
298 - PART II BASIC AND ADVANCED TECHNIQUES
phases is to count the baseline crossings in the waveform and fiber. A short rise time is therefore an indication that the record
add one. Usually phase assessment is quite simple, but signals ing electrode is placed inside the MU. In signal analysis, engi
may deviate minimally from the baseline after a crossing. This neers usually measure the rise time as the time from the baseline
is illustrated by '#' in Figure 8-6. In that MUAP one may count to the peak value of the signal. To exclude noise from these
5 phases by accepting the baseline crossing or ignore the small measurements, rise time may be defined as the time to reach
deflection of the potential and consider it to be triphasic. A 90-95% of the peak amplitude. In MUAP analysis, it is often rec
polyphasic MUAP has more than four phases. Conversely, a ommended that measured signals should have a short rise time.
simple MUAP has four or fewer phases. This is the most However, the definition of rise time is rather vague. It is usually
common form of description for the MUAP waveform. measured from the maximum positive to maximum negative
In computerized systems, the aforementioned measurements peak. This may not pose a problem for simple triphasic MUAPs;
can be made automatically. Algorithms in these systems detect however, for recordings made with the electrode in the endplate
the MUAP onset and end based on the slope of the signal and/or area, the signal may not have an initial positive peak. In a ser
its amplitude deviation from the baseline. To exclude small fluc rated or polyphasic waveform, the maximum positive and maxi
tuations about the baseline that result from noise, a minimum mum negative peaks may not occur successively. This can give
amplitude criterion should also be used in counting phases. a long rise time value (Fig. 8-6A).1O To overcome this problem,
Computers allow us to make additional measurements of the automated methods use the rate of change of voltage in a short
waveform.I84.185 A turn occurs at a peak of the MUAP. To ex segment of the MUAP to define this parameter. The rate is high
clude peaks generated by noise inherent to the recording, the when a MUAP has a short rise time and/or high amplitude.
signal must change by some threshold amplitude between suc Normally the MUAP waveform remains constant during suc
cessive turns. In Figure 8-6, the small peak in the rising edge of cessive MU discharges. Such MUAPs are called stable (Fig. 8
the waveform (indicated by the asterisk) does not fulfill this cri 7A). In contrast, an unstable MUAP changes waveform from
terion, hence it does not qualify as a tum. A MUAP is called one firing to another. This variability is quantified by a feature
serrated when it has more than five turns. A MUAP is called called jiggle, described in the single-fiber EMO section. The
complex when it is polyphasic, serrated, or both. 198 Other mea measurement of MU firing rate is discussed with the analysis
sures to describe the irregularity of MUAP shape are also de of interference pattern.
scribed. 221 Techniques. Several techniques are now available to extract
The area of the MUAP is measured between the rectified and quantify the MUAP waveform. We will focus on three dif
waveform and the signal baseline. The ratio area/amplitude ferent approaches that represent the evolution of these tech
quantifies the subjective assessment of the MUAP thickness. 131 niques. The first two methods are available on almost all
By combining the amplitude and ratio, a size index can be commercially available modern instruments. Regardless of the
computed. 172 extraction technique, the needle electrode is positioned to
In some recordings, the MUAP waveform may be divided record sharp and crisp-sounding EMO activity. This will also
into two or more portions that are separated by flat baseline increase the MUAP amplitude and reduce its rise time.
(Fig. 8-6B). In general, the longer duration portion (by visual In the manual method of analysis, the EMO is recorded at
assessment) is used for MUAP duration assessment, whereas minimal force of muscle contraction. Ideally, the signal should
the other portions are called satellite or linked potentials. A contain discharges of a single MUAP. An epoch of this signal is
satellite is separated from the main MUAP by baseline. If satel frozen on the instrument display for subjective assessment (Fig.
lite potentials are included in measurements of MUAP duration, 8-5). When the signal contains discharges of more than one
these may have very large values, which must be interpreted MUAP, manual analysis may become difficult. In Figure 8-8A,
with caution. The spike dnration is often measured between discharges of three MUAPs are identified by visual assessment
the first and last peaks of the MUAP, including any satellite or and appropriately labeled. MUAP #3 may not be used for analy
linked potentials. A spike duration that is longer than the MUAP sis due to very low amplitude. Activity from distant MUs results
duration indicates the presence of late spike components.
The rise time of the spike component of the MUAP reflects
the distance from the electrode to the nearest component muscle A B
~:3
A B
. . , (\'r-.: ' . .
.~ ~ ~ 3 2
.-l200~V mV
2m.
in small amplitude fluctuations on the baseline. making it diffi display of the MUAP on the display screen (Fig. 8-9D). One can
cult to assess the MUAP duration. Signals in B are a continua visually assess these time-locked discharges to assess MUAP
tion of the same recording but contain complex waveforms of features. This approach is often used to assess MUAPs during
long duration that are very different from the MUAPs in A. the routine needle EMG examination.
Unlike the waveforms in A. the complex waveforms in B do not For quantitative analysis, the trigger level is adjusted so that
repeat. Close scrutiny reveals that the waveforms in B are gen discharges of a single MUAP will appear time-locked on suc
erated by superimpositions of the MUAP waveforms seen in A. cessive sweeps (Fig. 8-9D). The other discharging MUAPs
This is a critical observation in manual MUAP analysis. In order appear randomly on the display. In this sense they are similar to
to be identified as a MUAP, a waveform must be seen to occur noise in the recording. When the time-locked sweeps are aver
at least three times. 3 It is quite unlikely that chance superimpo aged. the noise is reduced and a clean recording of the MUAP
sition of different MUAPs will result in identical waveforms wavefonn is obtained (Fig. 8-9E). This is similar to averaging
that are repeated within the analysis epoch. the sensory nerve action potentials to reduce the background
The manual method of MUAP extraction requires patient co noise. It is important to realize that the improvement in the
operation. Furthermore, duration measurements can be difficult signal-to-noise ratio (i.e., reduction in noise) is proportional to
when the baseline is noisy (Fig. 8-8A). A typical study may re the square root of the number of averaged sweeps. Most of the
quire over 30 minutes. noise reduction will be seen within the first 50-100 sweeps;
In the free-running mode of signal display (Fig. 8-8), individ therefore, every effort should be made to minimize the noise,
ual MUAPs appear at random positions on the sweep, making it i.e., the interfering MUAP, by having the patient sufficiently
difficult to assess their configuration (Fig. 8-9A). An amplitude relax the tested muscle. We would like to emphasize that the
trigger and delay line allow one to freeze discharges of a signal processing techniques should not be used to substitute for
MUAP on the display.39 This electronic device is operated as good recording techniques.
follows: The user defines an amplitude level (indicated by the When a triggered delay line is used, the amplitude level must
arrow in Figure 8-9B) using a control on the instrument panel. be set so that only one MUAP can trigger the sweeps, otherwise
If the EMG amplitude is less than this level, no signals are dis the sweep will be triggered by several different MUAPs and the
played. The display is "triggered" when the EMG crosses the resulting averaged signal will not be a true MUAP. Needless to
amplitude level. The signal immediately following the trigger say, this requires that the amplitude level be set high enough to
point is displayed until the sweep ends (Fig. 8-9C). The system be exceeded only by the largest-amplitude MUAP, whereas the
then waits for the next trigger to occur. When the amplitude trig lower-amplitude MUAPs are excluded from analysis. Other
ger is turned on and the amplitude level is set such that it is forms of triggering mechanisms have been developed to over
crossed by only one MUAP waveform, the EMG trace will be come this limitation. 39 A window or peak trigger defines two
drawn only when that MUAP discharges. The MUAP discharge amplitude levels and accepts only signals with maximum ampli
will occur at the same position in the display (Fig. 8-9C). This tude between these two levels. Signals that are smaller or larger
scheme does not allow visualization of the portion of the MUAP than both levels do not trigger the sweep.
waveform that precedes the trigger point. To accomplish this, This recording technique also requires considerable patient
the signals are passed through a device called a delay line, which cooperation. Furthermore, one must learn to manipulate the
adds a time delay before passing the signals to the display cir needle position and simultaneously adjust the trigger levels and
cuitry. A combination of these devices permits the time-locked control signal acquisition. Since the waveforms are displayed in
a time-locked fashion and averaged, the duration can be as
sessed better than in the manual method described earlier. A
+----Tr
c typical study may require over 20 minutes.
With access to fast digital computers, one can automate the
""'
.. ,. . . process of MUAP detection, extraction, and measurements
1 ' ' " , , considerably. This automated analysis is often called decompo
!---~
I
,\r- sition37.122 or multi-MUAP analysis (MMA).16.137 These tech
T niques are not available on most commercial systems. The basic
,,. ,
~s~P~
'""~,, r-.
d~1JI/·
'D'
strategies in this approach are as follows. First, a 5-20-second
EMG epoch is acquired and digitized (Fig. 8-1OA). Next the
signal is high-pass-filtered or differentiated (i.e., the rate of volt
...... age change is computed) to enhance the spike component of the
~
10ms r"
,v,
-oJ
signal (Fig. 8-10B). MUAP activity is detected when the
processed signal exceeds a threshold level. A portion of EMG
,B activity before and after this detection point is called a tem
.....
t ~
~
E plate. (This is very similar to the amplitude-trigger method de
scribed earlier.) After the templates in the signal have been
!1
!'
fr, ~ ~,
J ~~pv
21m identified, the first template is assigned to the "first class." The
I 20m1l I second template is compared with the first MUAP template. If it
is similar, it is assigned to the first class, otherwise it becomes
Figure '.9. Amplitude trigger and delay line. In A. a 300-ms the template of the "second class." The third template is com
epoch is shown in a free-running mode. The same signal is shown at pared with the first and second MUAP templates. It is either as
slower sweep speed in B. The arrow in B indicates the trigger ampli signed to one of those two classes or becomes the template for
tude level.The triggered sweeps are shown (C) without and (D) with the "third class." The process is repeated until all the MUAPs
a delay line. Three discharges are superimposed in D to facilitate sub have been assigned to a class (Fig. 8-1OC). Finally, the classes
jective assessment. The averaged MUAP is shown in E. that have more than a minimum number of matching templates
300 - PART II BASIC AND ADVANCED TECHNIQUES
~D
c than 12% polyphasic MUAPs. The mean values of amplitude
and duration were computed. Muscles with mean durations
within 20% of the normal mean were considered normal. Those
investigators excluded polyphasic MUAPs from calculation of
the mean MUAP duration, which gave higher diagnostic sensi
tivity for patients with myopathy,27,202,203
Figure 8·10. Principle of MMA.The signal in A is filtered (8) to While the data in Table 8-1 are impressive, it is important to
identify MUAP spikes. The dotted line represents the trigger level. The recognize some of their limitations. Although the values are tab
templates are indicated by the horizontal bars under the signal and are ulated for more than 20 age groups, data for many muscles were
labeled numerically.The templates form three classes. two representing obtained from far fewer than 20 subjects. Most likely, some of
MUAP discharges and a third that contains their superimposition (C). the values were obtained from regression analysis. This would
The first two classes have sufficient discharges to extract MUAPs (D). explain why the rate of change in duration values with age is
almost identical for many muscles. Finally, the duration values
for several muscles are extremely similar, occasionally identical
are considered to be comprised of MUAPs valid for analysis. (e,g., biceps = first dorsal interosseolls = soleus; gastrocnemius =
Their templates from the recorded signal (Fig. 8-10A) are aver extensor digitorum brevis; infraspinatus =flexor carpi ulnaris),
aged to obtain the MUAP (Fig. 8-1OD) and its features are mea Values within 20% of the mean are considered normal. Other
sured. An example of such an analysis is shown in Figure 8-11. studies show a 30% change from mean as the upper and lower
This approach requires less patient cooperation because it is normal limits (Tables 8-2 and 8-3; Figs, 8-12 and 8-13). The
not necessary to limit the activation to just one or two MUs as in change in MUAP duration with age is also less significant. 15,93,198
manual MUAP analysis. Furthermore, no instrument manipula Stewart and coworkers 198 used an amplitude-triggered delay
tion, such as trigger adjustment, is needed. One can easily line and averager to analyze MUAPs in the biceps muscle, The
obtain 3--4 different MUAPs from each recording, and with mean values of area/amplitude ratio and turns were also analyzed,
practice and experience it is possible to extract and analyze Only simple MUAPs were included in calculation of duration.
Amp Our
mV ms
t" 1c=JID CMl o:I]ITJ
12 ~1:::]1I1 12.601
1.3 ~c::Q;1IC]lQ]
Mean All c:::=:::J r=::::Q11 []]Ql
Sd All c:::=:::J c:::::Q] C]1Z]
.....n SIMPLE c=J c=::Q]] O]Q]
Sd SIMPLE c:::=:::J C]J]~
TotaIMUPs c:::=:::J c=J c:::::=J
'!foPolWbaslC c:::=:::J c:::=:::J
'!foSimple c:::=:::J c=J
Rate
~=:
, to
figure"" I. Example ofMMA,Analysis ofa IO-second epoch yielded 3 MUAPs.For each MUAp, the discharges are shown as if using a trigger
delay line. These can be seen in light gray color. The averaged MUAP is superimposed on these discharges in black.The superimposed discharges
make it easy to assess the validity of automated analysis. The tick marks represent the MUAP onset and endpoint. The MUAP measurements are
shown above the waveform and also in the result table to the right. The firing pattern is indicated in the lower right comer, where each tick mark
represents one firing of the MU within the IO-second epoch, Gaps in the firing pattern occur when the algorithm cannot resolve superimpositions
of different MUAPs,The user can edit the automated measurements or reject noisy MUAPs,
Chapter 8 QUANTITATIVE EMG - 301
sidered abnormal. CN. Concentric needle; MUAP, motor unit action potential
From Buchthal F: Electromyography in the evaluation of muscle diseases. In Fuglsang-Frederiksen A (ed): Methods in Clinical Neurophysiology. Vol. 2, Number 2-
The reference values are described graphically in Figure 8-12. of amplitUde was used to obtain a Gaussian distribution of the
These investigators found a much higher range of MUAP am data and to define reference limits. The distribution of the third
plitude (200-800 11V) than the data in Table 8-1. They also largest and third smallest amplitude values in individual deltoid
found up to 20% complex MUAPs in their normal data in con muscles of normal subjects is shown in Figure 8-14. These
trast to 12% by Buchthal and coworkers. The MUAP duration values are used to define the reference limits using the outlier
in their data increases slightly with age. The minimum to maxi principle. A study is considered abnormal when more than two
mum range is roughly ± 30% about the mean. Analysis of these outlier MUAPs are found. Some of the reference values for dif·
data is discussed later in greater detail. ferent muscles using this technique are summarized in Tables 8
The MMA technique is used extensively by Stalberg and 2-8-4.
coworkers. 193 They recorded 20-30 MUAPs from each tested Comparison of these techniques (Tables 8-2-8-4; Fig. 8-12)
muscle and found a slight increase in MUAP duration with age. demonstrates that different methods arrive at similar values for
The age dependency was different for different muscles (Fig. 8 normal MUAP duration. This is partly due to earlier attempts to
(3). This study also shows a roughly +30% variation about match the automated measurements with the reference values
mean as the normal range. The MUAP amplitude distribution was described in Table 8-1. The amplitude values are quite different
significantly skewed towards high values. Hence, the logarithm among these methods. This reflects the differences in selecting
iLLllLJ[i]ctJ,..---·~ "
I~ ~====···=··~~'I
II:]
6 .-: .,. •
• ,.' . , . 0,
.~
• • "5>.
- IO-
o 2000 h-:-I~"-L.J!JI ~----"';:'6;-'50
Amplitude{j.lVI Area {j.lV l msecl Ratio Turns Age (years)
Figure 8-12. Results of MUAP analysis. Results in a group of normal subjects are shown in the middle row. The mean values of amplitude,
area, area/amplitude ratio, and turns are presented as histograms. The arrows under the histograms indicate the normal limits. To the right, the
mean MUAP duration is plotted against age.The twO solid lines in these plots define the normal limits also. Plots like these are useful in comparing
studies from patients with myopathy (top row) and neuropathy (bottom row). (From Stewart C, Nandedkar SO, Massey JM, et al: Evaluation of an
automatic method of measuring features of motor unit action potentials. Muscle Nerve 1989; 12: 141-148. with permission.)
304 - PART II BASIC AND ADVANCED TECHNIQUES
From Bischoff C, Scllberg E, Falck B, Eeg-Olofsson K: Reference values of motor unit action potentials obtained with multi-MUAP analysis. Muscle Nerve
The statistics for the mean values from individual normal subjects is described.
From Barkhaus PE, Periquet MI. Nandedkar SD: Quantitative motor unit action potential analysis in paraspinal muscles. Muscle Nerve 1997;20:272-275. with permiSSion.
MUSCLENR: 26 Deltoideus
4.0
MUSCLENR: 26 Deltoideus
25,-----------------------------,
3.5
. .,. ~ ... •
3.0
~;:- .-!
I ••• 0- c:I • •
• .,0 "
~
2.5 S"''' ~Idb '!,D • D D
20 11 ...- a JI D
2.0
0
15 >
.::!..
1,5
~
0:::
1.0 amplitude outliers
10 sex
-e:
(\I
,5 D 3rd iowest
Ii)
<) female
~ 0.0 • :lrd highest
S ,5 o male
10 20 30 40 50 60 70 eo
c
0
e::l
'0 0
Total Popula'
Rsq ; 0,11!61
AGE
10 20 30 40 50 60 70 80
Figure 8-'4. MUAP amplitude. The outlier limits of MUAP ampli
tude in the deltoid muscle are defined based on the third largest and
third smallest value in normal subjects. Note the logarithmic scale. The
FIgure 8-13. MUAP duration. Multi-MUAP analySiS of the deltoid upper line is the upper limit of third highest ampliutdes (filled data
muscle of normal subjects shows a very slight increase in MUAP dura· symbols). The lower line is the lower limit of third lowest amplitude
tion with age. (open data symbols).
Chapter 8 QUANTITATIVE EMG - 305
normal
A B
•
I - • • •
••
~ ~
a .. a
-.0. 0
_g Q Q
a a it a • a
a _
I -
...e~ - • ....,.Q
•
n
neuropathy 0
-
25
C
••• , •
0
• • • •• •
-----:--:
0
15
---
~...
65
Aile! yeors)
-. •
•
• a
• •,f
•
•
• a
..
65
myopathy
~ +- --lfi---.-...-
--IN-- --\>-l- --M---- ~ ~ ~
-lfI--- --IN-- - - l r +
Figure 8·16. Diagnostic sensitivity of MUAP features. The
MUAP duration is plotted against age. The solid lines represent the
normal limits. See text for details. (From Stewart C, Nandedkar SO,
Massey JM, et al: Evaluation of an automatic method of measuring fea
-t+-- - I + - -t+-- -;.+- -jI..;- --t+-- tures of motor unit action potentials. Muscle Nerve 1989; 12: 141-148,
with permission.)
~ ---t/'+--- -1t- -;Iy-
MUAPs for analysis. The manual method works best when only
one MU is firing. In contrast, the MMA technique can analyze 25
3-4 different MUs in each tested epoch. The amplitude-trig
gered method is biased towards selecting the largest MUAPs. It c c c
c c c
is quite obvious that one must use reference data that match the 0 0
0
analysis technique. u
G) ~cg C
Clinical Findings. Regardless of the MUAP extraction tn 'co c
method used, many laboratories have demonstrated similar pat e ~Cr?D
D
terns of MUAP abnormalities in patients with neuromuscular
~rw.
c
diseases. 8•13•2 8.49.I03.165,192.193.194,198 We describe one such study in
greater detail to correlate the MUAP abnormalities with the MU
architecture abnormalities.
-
Q
0
....
0
::J
D
[]
C
middle row of Figure 8-12. The study by Stewart and coworkers discussion to include MUAP measurements and the disease
demonstrated increased amplitude and/or duration in patients processes that alter the MU architecture. The core of the CN is
with neuropathy; reduced amplitude and/or duration in patients covered by the cannula on one side (Figs. 8-3 and 8-18).
with myopathy; and increased incidence of polyphasic MUAPs Therefore, the cannula behaves as a shield for the high-fre
in both patient groups (Fig. 8-12). Similar findings are also re quency components of potentials arriving from the shielded
ported using other methods of quantitative MUAP analysis. side. The core records sharp, high frequency-rich potentials
These findings provide the basic criteria of MUAP assessment from muscle fibers that are in front it. For this reason, it has a
in the routine needle EMG examination. roughly hemispherical uptake area for the spike component of
The QA study by Stewart and coworkers 198 demonstrated the MUAP. It can record low-frequency components from all
some other interesting patterns of abnormality that are not read fibers around the core including those behind the cannula. 138
ily apparent. Although most patients with myopathy had normal These low-frequency components define the MUAP duration.
or reduced MUAP amplitude, a few studies showed a slight in The MUAP waveform also depends on the electrode position
crease in this feature (Fig. 8-12). The amplitude increase was relative to the endplates (Fig. 8-19).65 When recorded from the
much less than that seen in patients with neuropathy. When the endplate zone, the MUAP has an initial negative deflection (Fig.
amplitude was increased in myopathy, the MUAP area/ampli 8-19B). Away from the endplates, the MUAP has an initial posi
tude ratio was often reduced. In neuropathy, this ratio was tive deflection that signals an approaching potential volley. If the
normal or increased (Fig. 8-12). display gain setting is high, the abrupt onset of the MUAP from
In Figure 8-16, the MUAP duration is plotted against the pa the endplate area can be seen at any recording position (Fig. 8
tient's age. Horizontal lines indicate the normal limits. The filled 19B). Towards the end of the MUAp, one can also observe a pos
symbols indicate that there are abnormalities of MUAP features itive-going dip (Fig. 8-19C). This represents the arrival of the
other than duration. The data are divided into four groups based potential at the tendon. The waveform beyond this point repre
on diagnosis and muscle strength: (A) mild neuropathy, (C) sents the extinction of the action potentials. 56 If MUAPs are
moderate/severe neuropathy, (B) mild myopathy, and (D) mod recorded with high gain simultaneously at different positions
erate/severe myopathy. It is easily seen that QA has a higher di along the muscle fibers, the portions of the signal representing
agnostic sensitivity in moderately affected muscles (C, D) than onset in the endplate area and the arrival at the tendon are seen
in mildly affected muscles (A, B). In moderately affected mus simultaneously at all recording sites (Fig. 8-19B and C).
cles, the duration is more likely to be abnormal. Although the Computer simulations 132 (Fig. 8-18) indicate that the MUAP
MUAP duration was normal in many mildly involved biceps amplitude recorded by a CN depends mainly on the number and
muscles, there were abnormalities of amplitude, phases, and size of muscle fibers that lie within 0.5 mm of the recording tip.
turns (filled circles in A and B). In patients with neuropathy, The amplitude is sensitive to the size and distance of the muscle
many mildly affected muscles had MUAPs with high amplitude fibers closest to the active recording surface. Hence, a single
and duration (A). Furthermore. the relative changes in these fea muscle fiber close to the recording tip of the needle can produce
tures are quite different. The amplitude is increased almost 10 a normal or even increased MUAP amplitUde in myopathy.
fold, whereas the duration is only doubled (Fig. 8-17). Furthermore, the MUAP amplitude may change significantly
with slight changes in the recording electrode position. This is
MU Architecture and the MUAP Features demonstrated elegantly by the scanning EMG technique de
We have discussed the relationship between the shape of scribed later.
the MUAP and the MU architecture. We will now expand this MUAP amplitude is higher when the aforementioned uptake
area contains an increased number of muscle fibers from the
MU. This is likely to occur after reinnervation and/or regenera
Concenllic Needle tion of muscle fibers. Conversely, a reduced number of muscle
fibers yields a reduced MUAP amplitude. Of note, muscle hy
pertrophy generates a high AP amplitude. On the other hand, at
rophic muscle fibers have low amplitude potentials resulting in
smaller MUAPs. If the APs are synchronous, they summate
constructively, generating a high-amplitude MUAP. Increased
Duration - - - - : f - - - . J
temporal dispersion separates the individual APs, yielding
smaller MUAP amplitude.
Spike Shape _-+__-+-~"..,
high display gain (e.g., 10-20 JlV/div), one can see the potential
Amplitude --\---""""",,, onset at the endplate, its arrival at the tendon (the positive dip),
and its extinction at the tendons (Fig. 8-19, B-C). The MUAP
duration measured from its first baseline deviation (i.e., onset at
endplate) to its ultimate baseline return (i.e., potential extinction
at the tendon) is called the physiologic duration. 53- 56 This dura
tion is tens of milliseconds and reflects the time of potential
propagation, temporal dispersion of the potential, and extinction
of the potential, but contains little information about the effect
Figure B-'B. Uptake area of eN electrode. This schematic shows of pathology, hence it has minimal clinical value at this time.
the cross-section of an MU and a CN electrode tip.The shaded semicircu This technique also requires a very high signal-to-noise ratio,
lar areas enclose fibers that affect the MUAP amplitude and spike compo which cannot be easily achieved in routine clinical recordings.
nent.The shaded circle encloses the fibers that mainly define the MUAP In clinical analysis, MUAP duration is assessed at a lower
duration.These patterns were derived from computer simulations. display gain (e.g .• 100 or 200 JlV/div). This corresponds to
Chapter 8 QUANTITATIVE EMG - 307
Motor Neuron~
~on
Terminal Axon
NMJ Tendon
Branches
t t 2
t
3 4
t 5
t t 6
Electrode Position along muscle fibers.
B c
1
I\'---_---~-~I
. 1,\ • • •50ms)OOIl'l ~ '1
~~_____·__·{lIK~·__~·_____·__~_·~~~I~~·~-·---
~3______'.~~_.. ~_________ ~I~:I.I~·2~___.__~
50_m_$_20__
~ 50ms20~V
r\..: . ~Dm8'500~~ . \---,1' .
'!.
4 .
I':'-S---=---=~.:..........jl-:-...~,~~~.,----,--
lI
......
, __-I
5Dms2DOW
e . ~~ 5Om!5~
Figure 8-19. HUAP waveform at different electrode positions. In the biceps muscle of a normal subject, MUAPs were recorded at dif
ferent positions between the two tendons (8). For each MUAP the display gain (IJV/div) is indicated to the right of the trace. The vertical line
marks the same onset point at all electrode positions. Some MUAPs are shown with a higher display gain in C. The vertical line shows the same lo
cation of the potential generated when APs arrive at the tendons. The location of the needle within the MU for each MUAP is indicated in the
schematic (A).
using an amplitude threshold of about 10-20 IlV to detect the can significantly affect measurements of the total MUAP dura
onset and end of the MUAP. Measurements made in this tion, which poses a problem in duration measurements. Since
manner, conventionally called the MUAP duration, depend on these potentials are usually polyphasic because of increased
muscle fibers that are up to 2.5 mm from the recording tip of the temporal dispersion, one solution is to exclude polyphasic po
electrode. 132 This radius represents a substantial portion of the tentials from duration analysis. 8,13,27,28.202.209 Another solution is
MU territory (Fig. 8-18); therefore, changes in MUAP duration to exclude the linked potential from duration measurements.
reflect variations in the MU size. The number of MUAP phases and turns may increase due to
The MUAP duration increases if the number of muscle fibers temporal dispersion of APs from MU fibers that are within 1
from the MU that lie within the electrode territory increases due mm of the recording electrode tip.133 An increase in the number
to reinnervation, and decreases if there is a loss of muscle fibers. of fibers within this recording area improves the chance of ob
Changes in fiber size also affect MUAP duration. 133 Since hy serving a temporally dispersed MUAP. However, if these poten
pertrophic fibers generate large potentials, one would expect tials are synchronous, they yield a simple MUAP. Several
that they would produce an increase in the MUAP duration, architectural changes of the MU may increase the temporal dis
whereas atrophy of fibers should reduce the MUAP duration. persion of the MUAP: longer length of terminal axon branches
When fiber diameters vary, the temporal dispersion is signifi following reinnervation, slowed conduction in newly formed
cantly increased. The action potential of some muscle fibers axon sprouts, increased width of the endplate zone, slowed con
close to the recording tip may arrive at the electrode earlier or duction in atrophic fibers, or relatively fast potential propaga
later than other muscle fibers of the same MU because of fiber tion in hypertrophic fibers. In the case of dispersion due to fiber
size variation. A late-arriving muscle fiber potential may diameter variation, the polyphasicity is much more pronounced
appear as a satellite potential (Fig. 8-6). A single muscle fiber when the recording is performed remotely from the endplate
308 - PART II BASIC AND ADVANCED TECHNIQUES
350
70000
SF 300
60000
soooo·
Duration - - - / - - - _ j
~ 40000
Spike Shape _--+___.j,-_ _
{Tums & Phases} 30000
10000
WlC
"'"
250 500 750 1000 1250 1500 1750 2000
11 m
0.7
::L 0.02
0.6 1),()1S
0.01
zone. The number of phases is reduced if there is a severe loss ~O.5
o.oos
of muscle fibers. In this situation there may be just one muscle ~~~~~~==~~
the endplate area. For a very low threshold value (i.e., a very • • • • w • • • •
-..
N= 17 N = 11 N=6
:. •
:••
•
Formation of new I -
Loss ofMU &
Reinnervation - LossofMU &
Fractionation
N=6 N = 17 N = 13
• ••
••
I.
·1
a.
a-•
.
•• - .a••
•
••
Severe Trauma to Nerve Myopathy
figure 8-25. MU size and number in pathology. The distribution of MU size in a normal muscle is illustrated schematically. Observe the
change in the number and size of the MU due to disease processes.
three channels of bipolar EMG signals. These are used to iden The results of one such experiment in a normal subject are
tify almost every discharge of every MUAP contained in the shown in Figure 8-26. 195 This demonstrates quite vividly the
EMG signal. The force of contraction is also monitored. In a change in MU firing rate with the force of contraction. The
typical study, the subject gradually increases the force and then technique allows one to observe the high firing rate of MUs
relaxes the tested muscle. The process of decomposition is par (e.g., 30 Hz for MU 1) even at high force levels. With this tech
tially automated and does require some operator intervention. A nique we can also see that the last recruited MU stops
plot is constructed to demonstrate the relationship between the discharging first and vice versa. Although the individual MU
firing rate and force versus time. Several seconds of contraction firing rates are different, their firing rates change in parallel.
may require an analysis time of a few minutes to over an hour.
t. Biceps
50
&0
M .0
I;
A
A .s H"
N
r 30
r
0
I 30 R
e
"1 E
"G
II 20
20 •
~200PY
A
T M :
E Y
t 2_
; 10 10
5
Rgure 1-27. Recording for recruitment and firing rate analy
sis. Monopolar needle EMG recording in the biceps brachii muscle of a
o normal subject as the force of contraction was gradually increased and
2. 8 10 12 101 16 18 20 22
TIM E I H S·£ C 0 H 0 $ then decreased. Throughout the recording, the force of contraction
was minimal. Several different events can be recognized from this
Figure 8-26. Results of precision decomposition analysis. The epoch. A, Distant MU activity. B, MU # I is recruited. C, MU # 2 is re
solid line indicates the force of contraction.The dotted lines show the cruited. D, MU # 3 is recruited. E,The force of contraction is reduced.
mean firing rates of several MUs. Note the orderly recruitment and The firing rate of all MUs falls. F, MU # 3 stopped discharging. G, MU #
release of MUs, the high firing rates and the parallel change In their 2 stopped discharging. H, MU # I stopped discharging. It is difficult to
firing rates. (From Stashuk D, Deluca CJ: Update on the decomposition recognize discharges of MU # I in the presence of larger MUAPs from
and analysis of EMG Signals. In Desmedt jE (ed): Computer-Aided other MUs. MUAP identification by visual assessment of this 20
Electromyography and Expert Systems. Clinical Neurophysiology second epoch took the first author about 45 minutes. Firing rate analy
Updates. Basel, Karger, 1989, pp 39-53, with permission.) sis of these events is shown in Figure 8-28.
312 - PART II BASIC AND ADVANCED TECHNIQUES
18
16
2
,
,, ,,
•
MUll!
i.
MU.3
,,
4
•
3 4 5 6 7 8 9 10 11 12 13 14 15 16 11
Tme (Secondo)
· ·
A
· ·
.. ~1mv
· · · ~
~1~~~1~~~#~
· · - · --... . ·
B
· · · · . ·
B -...J l'-v ~
· · .
c '\ ~ 20~IJV
·
- .
I~
.10ms. ·
· ·
Figure '·30. IP signal at maximal effort. Concentric needle
EMG recording in the biceps brachii muscle of (A) a patient with my
opathy. (B) a normal subject, and (C) a patient with neuropathy. In my. FifUre 8-32. MU tiring rate assessment. In A. a Soo·ms epoch is
opathy, the IP is full with reduced amplitude. In neuropathy, the pattern shown as a single sweep. The same epoch is shown as 5 rastered
is reduced with fewer spikes and higher amplitude. For the normal IP sweeps of lOOms duration in B. Four MU discharges are recognized.
in B, a high-amplitude solitary spike (*) is easily recognized. which gives an 8-Hz firing rate.
314 - PART II BASIC AND ADVANCED TECHNIQUES
~
................. ..
............
Analysis of the IP at maximal effort requires patient coopera
tion. If the patient cannot deliver maximal effort due to pain or - ...
~
other factors, the IP may appear incomplete and have a low en ....... .
~n_t!~~_ - :.. 1
•• --------.--.---,.. 1
velope amplitude. This cannot be considered abnormal. In such ...... ~.
situations, the assessment of MU firing rate and MUAP analysis 200IIV 200IlV:
. . .. . . .
is of great value. 10ms 10rns
Pitfalls. The fuIJness and envelope amplitude measurements
are inherently subjective and hence the assessment may vary Figure 8-34. Onset and recruitment frequency. Monopolar
among different investigators. The display settings can also needle EMG recording in the biceps brachii muscle of a normal sub
affect the assessment of IP fullness. If the display gain is low ject.The onset of MU #1 is seen in A and recruitment of MU #2 is
(e.g., > 2 mV/div) one may not be able to see MUAP spikes in seen in B.
the EMG. This can give an impression of a reduced IP (Fig. 8
31 C). If the sweep duration is long, it will contain more MUAP
spikes compressed within a small portion of the display, which the interval between successive discharges of the same MU is
will make it look more dense (Fig. 8-3IB). Therefore, subjec lOOms, i.e., one sweep duration. Hence the MUAP will appear
tive IP assessment should be performed at a standardized dis at approximately the same place on each sweep (Fig. 8-33B). If
play gain and sweep speed. the discharge rate is less than 10Hz, the MUAP will appear to
shift to the right on successive sweeps (Fig. 8-33A). If the inter
IP Analysis at Minimal Effort val between successive discharges, called the interdischarge
Technique and Measurements. At minimal effort one can interval (IDI), is longer than lOOms, there may be some
recognize and quantify the recruitment of individual MUs and sweeps with no MUAP discharge (Fig. 8-33A, bottom trace).
their firing rates. 148 A simple way of estimating the MU firing Conversely, the MUAP will appear to shift to the left when the
rate is to display a 500-ms epoch on the screen. This may repre ftring rate is more than 10 Hz (Fig. 8-33B). In this case, the 1DI
sent one single sweep with a slow sweep speed (Fig. 8-32A) or is shorter than 100 ms and on some sweeps the MUAP may be
several rastered sweeps at a faster sweep speed (Fig. 8-32B). seen twice (Fig. 8-33B, top trace). When the MU firing rate is
Individual MUAP discharges are identified by visual inspection. 20 Hz, one can see two MUAP discharges on each sweep (Fig.
The number of discharges of the MU in this half-second epoch 8-37B).
is multiplied by 2 to get the firing rate. The firing rate of an MU when it is frrst recruited is called its
If the sweep duration is set to 100 ms, the MU firing rate can onset frequency (Fig. 8-34A).145 In contrast, the firing rate of
be assessed using some simple rules. At a firing rate of 10Hz, an MU when another MU is first activated is called the
recruitment frequency,145 To compute the recruitment fre
quency, the two discharges of the earlier recruited MUAP just
A B
. ~; . . . . . . . A B
~'.~.-.-.-
. l BICEPS
, 1. .
,
" .., ' . . . ~I • • • •
~vv--------
. . ' ... ,,'.. . . .... .
.'
10ms
....... , 200pV
10ms .1 A . . 2,~ ,1 A T .2 h
".~~~:-
Figure 8-33. MU firing rate assessment. In A, the MUAP is dis 10ms
charging at 8 Hz. The dotted line parallels the progressive shift in
MUAP position to the right, indicating that the firing rate is less than Figure 8-35. Recruitment ratio measurement. In A. monopo
10 Hz. In B, the position of the smaller MUAP is relatively fixed on the lar needle EMG recordings in the biceps muscle of a normal subject at
screen, paralleled by the vertical dotted line. indicating that the firing minimal effort are shown. Discharges of three MUs are identified and
rate is 10Hz.The position of the large amplitude MUAP shifts pro labeled.A similar recording from a patient with neuropathy is shown in
gressively to the left, paralleled by the other dotted line. indicating that B. The recruitment ratio is .. (Le., 12 Hzl3 MU) in A, and 9 (18 Hzl2
the rate is greater than 10Hz. MU) in B.
Chapter 8 QUANTITATIVE EMG - ll5
50 cated for different muscles. At the bottom, the measurements are compared
F= 0.58 From Petajan JH. Phillips BA: Frequency control of motor unit action potentials.
0
0 50 100 150 200 250
MSEC
(101) vary slightly from one MU discharge to next. This vari
Figure B-36. 101 analysis.A scatter plot of the interdischarge inter ability is quantified by computing the coefficient of variation of
val (101) versus the previous 101 shows (A) negative correlation and the IDI (Le., SD/mean). This calculation represents the overall
(8) positive correlation. (From Shahani BT,Wierzbicka M, Parker SW: (or long-term) variation in the firing rate. To study the instanta
Abnormal single motor unit behavior in the upper motor neuron syn neous or short-term variation, a plot of IDI versus the immedi
drome. Muscle Nerve 1991;14:64-69, with permission.) ately preceding lDI is constructed (Fig. 8-36). The correlation
coefficient and other statistics of this plot may also be com
puted. 71 ,162.216 This analysis has not been introduced into routine
before the activation of next recruited MUAP are identified assessment of the EMG pattern.
(Fig. 8-34B). The time difference between those discharges is Clinical Findings. The statistics of onset and recruitment in
the recruitment interval. When the interval is measured in mil terval in different normal muscles is summarized in Table 8-6.
liseconds, the frequency is obtained by the formula Review of the distribution of these measurements (Fig. 1 in
Petajan, 1974) suggests a normal range of 5-12 Hz for onset
Recruitment frequency (Hz) = l000/recruitment interval
frequency and 7-16 Hz for recruitment frequency. In a patient
When several MUs are discharging, the recruitment
ratio41.43 is calculated by dividing the number of discharging
Table 8-7. Antigravity Testing
MUs into the firing rate of the most rapidly discharging MU
(Fig. 8-35). Subject Group # MUs # Spikes/sec
Petajanl47.148 proposed the antigravity 45° test to assess the Control 4.2 ± 1.6 ...o± 20
recruitment. The EMG was recorded when the patient main
tained the forearm at 45° angle and overcame the gravity. He
Neuropathy 3.2 ± 1.7 29 ± 20
identified all MUs that had MUAP amplitude of more than 100 Dystrophy 8.3 ± 2.4 122 ± 42
IlV. The number of MUs, their firing rates, and the total number Polymyositis 6.8 ± 2.6 76 ± 29
of MUAP spikes per second were counted by visual inspection. The mean and standard deviation values of measurements in different patient
Even when the force of contraction is maintained constant, groups are compared. Note that only spikes with more than 100 !IV amplitude
the MU firing rate is not constant. The interdischarge intervals are used in analysis,l~1
316 - PART II BASIC AND ADVANCED TECHNIQUES
A
B A B
l--'l.~ t . -~-'tt ·
...~ .,
~I
h F ""
I~
,I I
I~··I.
1~~->1A.5-'--""-'Il't-........,.,~1-~1
. . 'n' . . .A' . A' 1. I '. .L . .* .
~~~lr-, ~ .1 .. t~_··5
i~" i i0 ~v .~. . . n 1 . l~ il mit '1',
.. r::::::r·
... ~~j
... j
1 . .. j
1 4 1 mV
\
. . . ,oms 10ms.
Figure 8-37. Firing rate analysis in disease. Concentric needle Figure ...38. Calculation of recruitment ratio in myopathy. A
EMG recording in the biceps muscle of (A) patient with neuropathy 500-ms epoch of CNEMG recording at minimal force is visually exam
and (B) patient with inflammatory myopathy. Both recordings demon inated to identify discharges of different MUAPs. In A, 5 MUAPs are
strate single fast firing units corresponding to increased recruitment identified, discharging at less than 10Hz. The recruitment ratio is less
frequency. This finding is atypical for myopathy, but can be seen in se than 2.ln B. even at minimal force, many MUs are recruited. It is rather
verely weak muscles.The asterisk indicates low-amplitude MUAPs that difficult and cumbersome to analyze this epoch for computing the re
are not easily recognized. If we could analyze them the recruitment cruitment ratio.
frequency could be normal.
group Petajan l46 found reduced values of onset and recruitment frequency. Let us assume that the second through sixth recruited
intervals. This corresponds to a higher MU firing rate (Table 8 MUs are lost. Our measurement of recruitment frequency in this
6). The increased onset and recruitment frequency is readily muscle will correspond to the firing rate of the first recruited
seen in patients with neuropathy (Fig. 8-37 A). It is more appar MU when the seventh MU just begins to discharge. The result
ent in severely affected muscles of patients with myopathy (Fig. ing higher values of recruitment frequency also mean that single
8-37B). The recruitment ratio is increased in patients with neu fast firing MUs will appear during the routine needle EMG (Fig.
ropathy (Fig. 8-35B). In patients with myopathy, the recruit 8-37 A). The reduced number of MUs allows us to observe their
ment ratio may be nonnal or reduced (Fig. 8-38). discharge at higher rates. Furthennore, the number of MU s con
The results of antigravity posture EMG recordings are sum tributing to IP is reduced. This combination leads to calculation
marized in Table 8_7. 141 The patients with myopathy recruited of an increased recruitment ratio (Fig. 8-35B).
more MUs compared to nonnal and gave increased number of The greater the loss of MUs, the easier it is to make these
spikes in the recording. A contrasting pattern was seen in pa measurements. When measuring recruitment frequency, it is not
tients with neuropathy. necessary to demonstrate recruitment of a second MU. A single
In nonnal subjects, a scatter plot of successive IDI values MU discharging at more than 20 Hz implies that the recruitment
demonstrates a negative correlation (Fig. 8-36A). In other frequency is even higher than this (Fig. 8-37A). If two MUs are
words, a short IDI is followed by a long IDI and vice versa. In discharging at more than 15-20 Hz, we know that the recruit
patients with upper motor neuron disease the MU firing rate ment ratio is increased (Fig. 8-35B).
variability is increased. A positive correlation between succes In a weak muscle, a patient with myopathy may activate sev
sive lOIs may be seen in some of these patients (Fig. 8-36B). eral MUs even at minimal effort. This results in a reduced re
Clinical Interpretation. In the free-running EMG display, a cruitment ratio. The MUAPs may appear to fire at slightly
MUAP is recognized by its main spike amplitude. As discussed higher than nonnal rates; however. because the number of dis
earlier, the MUAP amplitude is defined by the number and size charging MUs is increased, the recruitment ratio is nonnal or
of muscle fibers within approximately 0.5 mm of the electrode. reduced. In a myopathy, the primary pathologic process is
This area may contain 1-4 fibers belonging to a nonnal MU.132 muscle fiber loss. If the MU has lost 2 or 3 fibers that would
As a result, the electrode can record sharp detectable MUAPs have been close to the needle tip. it will generate a low-ampli
from over 20 different MUs that lie,near the needle tip. The dif tude MUAP that may not even be detected. If the majority of
ferent MUAPs can superimpose, making it difficult to recognize fibers are lost from a MU, the MUAP may be too small to be de
their individual wavefonns. When more than 3 MUs are re tected during the recording. This has the same effect as loss of
cruited. assessment of their wavefonns and firing rate by visual MUs and increases the calculated recruitment frequency (Fig.
observation may not be possible within the time constraints of 8-37B).
the EMG examination. Therefore, in nonnal muscles we can re Submaximal effort gives an incomplete or reduced pattern.
liably assess MU firing rates only at minimal effort, when they When this occurs, the analysis of MUAP wavefonns and firing
discharge at low rates. Precision decomposition studies, how rates can be quite useful. Patients with upper motor neuron dis
ever, reveal that nonnal MUs can discharge at much higher fre ease may not be able to recruit all their MUs and hence the IP
quencies (Fig. 8-26). pattern is incomplete. However, the MUs that are activated tend
In the clinical setting, it is possible to observe MUAPs firing to discharge at slower rates and their discharge pattern is irregu
at high rates if the number of MUs near the needle tip is re lar. In contrast, when nonnal subjects produce an IP that is in
duced, e.g., in patients with neuropathy. There is a high recruitment complete, MUAPS have nonnal waveforms and a rhythmic
Chapter 8 QUANTITATIVE EMG - 317
Attp CMU)
3.5
-3.5
o 1.00
AttDI'Turn (uU)
SOO.O
0.0
0.0 1350.0 o 0.01
Turns C....s)
0.0
0.0 1000.0
Activity C_)
Figure 8·3'. Different methods of IP analysis. An epoch of IP signal from a normal biceps brachii muscle is shown at the top. The power
spectrum of this signal is shown in the middle right plot. The dashed line in this plot indicates the median frequency. The wms and ampliwde
(TA) analysis from the same muscle is shown in the left middle plot. More than 90% of the data points fall within the normal cloud.The expert's
quantitative IP (EQUIP) analysis in the same muscle is shown in the lower two plots. The data show a normal distribution, with fewer than 10%
of the data points are outside the clouds. (From Sanders DB, Sd.lberg EV, Nandedkar SD:Analysis of electromyographic interference pattern. J
elin Neurophysiol 1996; 13: 385-400, with permission.)
firing pattern. In patients with lower motor neuron disease, the calculation of the recruitment ratio. When several MUs are dis
MUs appear to discharge faster (Le., increased recruitment fre charging, their MUAP waveforms superimpose, making it diffi
quency and ratio) and the MUAP waveform shows changes due cult to identify individual MUAPs and their firing rate,
to denervation and reinnervation. especially if the MUAP amplitude is low (Fig. 8-38B).
Pitfalls. A MUAP is recognized mainly by its spike compo
nent, which is generated by muscle fibers closest to the needle Power Spectrum Analysis
tip. The EMG signal also contains small-amplitude MUAPs of Technique and Measurements. The sound of the EMG
distant MUs that are often ignored. Unfortunately, there is no signal is very helpful in assessing the IP. Walton211 used an audio
formal criterion to include or exclude MUAPs in the firing rate spectrometer in the early 1950s to demonstrate a shift to high
analysis. This affects the assessment of the recruitment ratio and frequency components in EMG signals from patients with my
the recruitment frequency. Signals in Figure 8-35B appear to opathy. The technique of frequency spectrum analysis can now
contain discharges of a single MU firing at a high rate. be carried out quite easily using digital computers. In this
However, if one accepted the smaller amplitude MUAPs in the method, also called Fourier analysis,31,32,99 the IP signal is rep
signal, the recruitment would be considered normal. Similarly, resented as the sum of harmonically related sinusoids. A plot of
the inclusion or exclusion of MUAP 3 in Figure 8-8 affects the the power (measured as squared amplitude) for each sinusoid
318 - PART II BASIC AND ADVANCED TECHNIQUES
the values found in normal subjects and plotted against the fre
quency. The four normalized values are close to unity for
normal IP signals, and the line connecting them has a slope
close to zero. When the spectrum shifts to high frequencies, the
normalized power for that band exceeds 1 and the slope is posi
tive (Fig. 8-40). The slope of this line can also be used to assess
the severity and progression of the disease.
Clinical Findings. In myopathy the mean and median fre
quency values are increased, indicating a shift towards higher
frequencies (Fig. 8-41). In neuropathy these frequency parame
ters shift to lower values (Fig. 8-42). In all subjects, fatigue in
creases the power in the signal and shifts the spectrum towards
low frequencies. 38.105.109.218
Clinical Interpretation. The shape of the component
MUAPs affects the power spectrum. Polyphasic MUAPs with
short rise times and short durations give rise to high-frequency
components. In contrast, long-rise-time, long-duration MUAPs
give a dull sound to the EMG, Le., there is a shift to low fre
quencies. This explains the typical patterns of shift in the spec
trum observed in pathology. The total power reflects the number
of activated MUs and their MUAP amplitude, thus it increases
with force of contraction. During fatigue, the shape of the
MUAP changes due to alterations in the intracellular action po
tential. This gives a shift to low frequencies and increased
0.0 . power in the signaL Although a high-pitched souQd of the EMO
50200 800 1600 Hz is usually associated with myopathy, it may also be heard in
neuropathy due to increased incidence of polyphasic MUAPs.
Figure 8-40. IP analysis using a broadband filters. The shaded
Pitfalls. The mathematical transformation in the power spec
area represents the normal range of normalized power values in the
trum analysis makes the measurements less intuitive. For exam
four frequency bands. The line has a positive slope, indicating a shift to
ple, one can look at a signal and estimate its envelope
wards high frequencies. (From Sandstedt P. Henriksson KG, Larsson
amplitude. However, it would be difficult for many to estimate
LE: Quantitative electromyography in polymyositis and dermatomyosi
the mean or median frequencies. Finally, we are unaware of
tis.Acta Neurol Scand 1982;65:110-121,with permission.)
well-defined reference values for this technique based on a large
number of control subjects.
against its frequency is the power spectrum (Fig. 8-39). (It is cus
tomary to use logarithmic scales for these measurements to ac Turns and Amplitude Measurements at Fixed Force
commodate the wide range of frequency values.) Analysis based Technique and Measurements. Power spectral analysis,
on the spectrum is often called the frequency domain approach. though elegant and fascinating, is rather abstract and too mathe
The sum of the powers in individual sinusoids, i.e., the area matical for routine EMO assessment. In the early 1960s, it was
under the spectrum curve, is the total power in the signal. The also time-consuming, and time domain measurements were fa
median frequency divides the spectrum into two halves. The vored. These measurements are made from the actual EMO
mean frequency is computed as: (!: Frequency x Power)ffotal waveform rather than its mathematical manipulations. A simple
Power. time domain measurement is the EMG amplitude. A signal with
Fourier analysis computes the power in hundreds of narrow high median frequency should have more peaks. However, peaks
frequency bands. Considerable data are generated by this tech may also be generated by noise. To exclude noise, Willison 215 de
nique, but most are not analyzed due to practical limitations. fined the so-called turn of the IP signal (Fig. 8-43).
Instead, simple calculations, such as the mean or median fre • A turn occurs at the peak of the IP signal.
quency, are performed. Sandstedt and coworkers 159 used a • If a turn occurs at a positive-going peak, the immediately
simple approach in which the power was measured in four previous and next turns will occur on a negative going peak,
nonoverlapping bands. These measurements were normalized to and vice versa.
. . . . (flU)
.I.
-.I.
a T .... _,
a.a ~~~L-~~~~~~
D.a
Activit" <_,.l.DDD.D
Figure B-41. IP analysis in a patient with myopathy. An epoch of IP signal from the biceps brachii muscle is shown at the top. Note the low
amplitude and increased number of spikes.The power spectrum shows a shift to high frequencies (middle right plot). In the TA analysis from the
same muscle (left middle plot), more than 10% of the data points fall outside to the lower right side of the normal cloud. The EQUIP analysis
(lower two plots) demonstrates a full pattern (activity> 500 ms) with reduced amplitude and increased number of small segments (NSS) (i.e .• a
shift to high frequencies). (From Sanders DB, Sdlberg EY, Nandedkar SD:Analysis of electromographic interference pattern. j elin Neurophysiol
1996; 13:385-400. with permission.)
• Successive turns are separated by at least 100 }.tV of ampli used a fixed load for manual resistance, e.g., 2-kg weight for the
tude difference. biceps brachii. In contrast, Fuglsang-Frederiksen and col
In addition to the number of turDS per second (NT) one can leagues72•13,14,15 used 30% of the force generated by the patient's
also quantify the amplitude difference between successive turns. maximal effort as the force level for testing (Table 8-9). The
The average value of this measurement is called the mean am latter group also measured the NTIMA ratio and number of
plitude (MA). short-duration intervals. Both groups recorded the IP signals at
In the biceps muscle, the NT increases linearly with the force different sites within the tested muscle. The mean values of
of contraction until it is roughly 50% of maximum (Fig. 8-44, measurements were compared against reference values derived
Table 8-8). At higher force levels it may increase slightly further from normal subjects.
or may even decrease slightly. The MA usually increases with Clinical Findings. Willison and coworkers observed in
force through all levels of contraction. creased NT in dystrophy and increased MA in neuropa
Since the measurements depend upon the force of contraction thy.87,88,152,215 Fuglsang-Frederiksen and coworkers 72- 15 made
(Table 8~8), recordings for TIA analysis are performed at a standard similar observations. In addition, they reported an increased in
ized level of muscle activation. Willison and coworkers87,88.152.215 cidence of short-duration intervals in myopathy. They found the
320 - PART II BASIC AND ADVANCED TECHNIQUES
AMp ~(MU~~)~____-+___Neu
__ ____t~hw~__~____-+____-r-;__~~__~__--,
rropa
2.5
-2.5
o
......=J.34Mz "_U.rt=J.OIJtb
)C .--r
1.4
---
0.0
0.0 1.350.0
Turns (1'..)
--
1.0.0 000.0
-, -
..
0.0 0.0
0.0 1.000.0 0.0 1.000.0
Activity < - ) Activity <-)
figure 8-42. IP analysis in a patient with neuropathy. An epoch of IP signal from the biceps brachii muscle is shown at the top. Note the high
amplitude and reduced number of spikes. The power spectrum shows a shift to low frequencies (middle right plot). TA analysis from the same
muscle (left middle plot) shows that more than 10% of the data points fall outside on the upper side of the normal cloud. EQUIP analysis (lower two
plots) demonstrates a full pattern (activity> 500 ms) with increased amplitude and reduced NSS (i.e.• a shift to low frequencies). (From Sanders DB.
Sdlberg EY, Nandedkar SD:Analysis of electromographic interference pattern. J Clin Neurophysiol 1996; 13:38.5-400. with permission.)
Table 8·9. Reference Value of IP Analysis curved boundaries. Since the regressioI\.line continues indefi
Parameter Biceps Brachii Vastas Medialis TibialisAnterior nitely. upper limits of NT and MA are also defined to truncate
Female Male Male/Female Male/Female the cloud at the right and the top.
Clinical Findings. In patients with neuropathy (Fig. 8-42),
Subjects 28 33 12 14
some data points fall outside and on the upper side of the
NT 478 ± 67 533 ± 57 471 ± 31 438 ± 56 normal cloud. Data points inside the cloud tend to lie near the
MA 440 ± 67 542 ± 76 581 ± 103 580 ± 102 upper edge of the cloud. In contrast, in patients with myopathy
1.10 ± 0.13 1.0 ± 0.14
(Fig. 8-41), data points tend to lie near the lower border or
NT/MA 0.82 ± 0.14 0.77 ± 0.11
below the normal cloud. Some data points may lie to the right of
The mean and standard deviation of different IP measurements in normal sub the normal cloud. The normal clouds for some muscles are
jects are summarized. The force of contraction was 30% of maximal effort.
From Buchthal F: Electromyography in the evaluation of muscle diseases. In
shown in Figure 8-45.
Fuglsang-Frederiksen A (ed): Methods in Clinical Neurophysiology. Vol. 2. A study is abnormal when more than two data points out of
Number 2. DANTEC Elektronik, Skovlunde (Denmark). 1991. with permission. 20 are outside the cloud. This could occur within the first two or
three sites. in which case quantitative IP analysis in the tested
muscle can be concluded at this stage. In this respect, the quan
femoris muscle of children suspected of having neuromuscular titative analysis would not add significantly to the time of the
disease. In uncooperative subjects, the muscle activation was EMG examination.
achieved by tickling the child or having them kick a toy. Cliuical Interpretation. The contrasting patterns of data
Patients with no objective evidence of disease were considered point distribution in different disease states make TA useful in
as "apparent normal" and used to define the reference values. differentiating myopathy from neuropathy. Computer simula
The normal range of mean MAINT ratio was 0.521-1.071 J70 tions have been used to study these changes in the NT and
Gilchrist and coworkers80 also found the MAINT ratio useful in MA. J28 Initially the NT increases with the number of MU dis
the IP analysis in adult subjects. charges, i.e., the number and firing rates of the MUs. When sev
Stalberg and coworkers lS2 used a similar approach of record eral MUs discharge at high rates, their MUAPs superimpose.
ing, but a different way of assessing the abnormality of mea When large- and small-amplitude MUAPs superimpose, the re
surements. In their technique, now called turns and amplitude sulting signal resembles the larger MUAP (Fig. 8-46). The
(TA), the IP signals are recorded at different force levels rang small MUAP is masked and we cannot see its turns. In other
ing from minimal to maximal at each tested site. The turns per words, the summated waveform has fewer turns than the sum of
second (Le., NT) and mean amplitude between turns (Le., MA) turns in individual MUAPs. Hence, the NT does not change sig
are measured. A total of 20 or more data points are obtained nificantly at high force levels (Table 8-8). The reduction in NT
from 6-10 different tested sites in the muscle. A plot of MA values also corresponds to a slightly "dull" sound of the IP
versus NT is constructed. An area on this plot is defined, called recorded at high force levels.
the normal cloud, which contains more than 90% of data points The reduced NT in neuropathy reflects a reduced number of
from each normal subject (Fig. 8-39). A study is considered ab MUs. The MA is increased due to higher MUAP amplitude after
normal if more than 10% of the data points are outside the reinnervation. In contrast, the NT in myopathy is normal or in
normal cloud (Figs. 8-41 and 8-42). creased (data points to the right of the cloud). This reflects a
The normal cloud (Fig. 8-45) is defined by performing linear normal number of MUs and polyphasic waveforms. When the
regression between the NT and MA (or their logarithms) and se amplitude of MUAPs is reduced, as seen by a reduced MA,
lecting a standard deviation band that contains the desired per there is less masking of the smaller MUAPs. This also gives
centage of data points. When logarithms are used to calculate more turns in the signal.
the regression, the standard deviation bands give the clouds Pitfalls. In the TA method the normal clouds depend on the
type of electrode used, and the patient's age and gender.
Normal clouds have been defined for only a few muscles,
A B which limits the use of this technique. The normal clouds also
appear to depend upon the technique of force measurement.
Men Amplitude (IIV)
1200 1 StaIberg and coworkers l82 used manual resistance against the
patient to get the necessary force. This may not be adequate to
1000 -j
get maximum contraction of the tested muscle, especially when
the subject is stronger than the examiner. Nandedkar and
coworkers l35 had the subject pull against a strain gauge to reach
maximal effort. The latter approach gave a much higher values
of amplitude that fell outside the normal cloud of StAJberg et
T al.1 82 (Fig. 8-47). The difference was seen mainly at high force
~.. ~ 200
levels. Due to such differences, it is recommended that one de
$-rnHCi' 0, r'~
.T . 0 200 400 600 BOO 1000 velop his or her own reference values for this technique, which
T Tums I Second is a significant undertaking.
Figure 8-44. Turns and amplitude change with force. A, The Other Techn;ques Based on Turns and Amplitude
peaks in an IP signal epoch were analyzed to find turns, indicated by T. Many other strategies have been used to increase the diagnos
The asterisk indicates peaks generated by noise. B, The change in the tic sensitivity of the TA analysis and to make it independent of
number of turns and mean amplitude at two different sites is shown. force of contraction75 ,79 Liguori and coworkersl07.108 monitored
The measurements were made at minimal, mild, moderate, and maxi the NTIMA ratio as the force of contraction was increased grad
mal effort.The data points from each site are connected. ually from minimal to maximal. The peak value of the ratio was
322 - PART II BASIC AND ADVANCED TECHNIQUES
NORMAL MATERIAL
MALES FEMALES
BICEPS
EDC
QUADRICEPS
TIBIALIS ANTERIOR
Figure 1-45. Normal clouds for different muscles in CNEMG study. The cloud with square data points is used for patients over 60 years.
(From Sdlberg E, Chu j, Bri! V. et a1:Automatic analysis of the EMG interference pattern. Electroencephalogr Clin Neurophysiol 1983;56:672-681,
with permission.)
determined for each tested site. This usually occurred at moder measures the portion of a I-second epoch that contains spiky
ate effort (Table 8-8). The peak: ratio was increased in myopathy MUAP signals. The activity values range from 0 to 1000 ms.
and reduced in neuropathy. The diagnostic sensitivity was The greater the numerical value, the more full/dense the pattern
higher in patients with myopathy. by subjective assessment. As with ful1ness by subjective assess
Gilai79 plotted the total amplitude change (Le., NT x MA vs. ment, the normal value of the activity parameter differs between
the NT values). The slope of the mathematical curve fit for the muscles. The envelope amplitude was computed by discarding
data distribution was computed. The slope value was increased extreme peaks, which potentially represent superimposed
in neuropathy and decreased in myopathy. MUAP signals. l34 The NSS represents the number of short-du
ration, low-amplitude segments between successive turns. This
Expert's Quantitative IP (EQUIP) Analysis quantifies the high-pitched audio characteristics of the IP. The
Technique and Measurements. The previously discussed data for EQUIP analysis were acquired and analyzed similar to
quantitative measurements of the IP are quite different from the that of TA, i.e., by constructing plots of amplitude and NSS
subjective descriptions of the IP such as "fullness" and quality versus activity (Fig. 8-39).
of the sound. Therefore, Nandedkar and coworkersl28.129 devel Clinical Findings. This technique of analysis is called
oped three parameters of the IP to measure features of the IP expert's quantitative IP (EQUIP) since it aims to mimic the
that are subjectively assessed: activity, envelope amplitude, subjective assessment performed by an expert electromyogra
and number of small segments (NSS). The activity parameter pher. In myopathy (Fig. 8-41), the activity values are high (>
Chapter 8 QUANTITATIVE EMG - 323
8ICEPS
f\
2500
I\
------.J '---_-~ 1
~----------____ 2
---
>::0
E
'--____- - - 3
::
j
-
o
'--_----6 o Turns Usee) 1250
I
al. m (From Nandedkar SO. Sanders DB. Sdlberg EV: On the shape of
the normal turns-amplitude cloud. Muscle Nerve 1991; 14:8-13. with
permission.)
7
~
recording surface of the electrode. Hence, a newly recruited MU
may have lower- or higher-amplitude MUAPs compared with
10 other discharging MUAPs depending on how close its fibers are
to the electrode (Fig. 8-49). When the newly recruited unit lies
1----1
Sma close to the electrode, its recruitment may be recognized quite
easily on visual assessment as an increase in the envelope am
Figure 8-46. MUAP waveform interaction. A large (I) and a plitude. The small amplitude MUAPs of later recruited MUs
small (2) MUAP were summated (3-10) by computer simulation. Note contributes to the NT. NSS, activity, and fullness of the pattern,
that the summated response resembles the large MUAP when the but not to the envelope amplitude.
MUAPs occur close to each other (+-8). The summated waveform
contains fewer turns than the turns in the individual MUAPs. Note that
the amplitude of the summated MUAP (6) is not significantly greater
than that of the large component MUAP. (From Nandedkar SO.
Sanders DB. Stilberg EV: Simulation and analysis of the electromyo
graphic interference pattern. Part I: Turns and amplitUde measure
ments. Muscle Nerve 1986;9:419-426. with permission.)
A B
. . . 1'~..
. 1 . . .
~'v-:--:--:-
.
~
. ..
, .,
. 1
~500"V
~2~1l~ SOm.to
10ms
Figure 8-50. Bimodal amplitude. IP recording at maximal effort
Figure 8-49. Amplitude of second recruited MUAP. in the biceps brachii muscle of a patient with myopathy shows mostly
Monopolar needle EMG recordings at two sites (A. 8) in a normal low-amplitude MUAPs. One MUAP has a thin waveform with high am
biceps brachii muscle. In A, the MUAP of the second recruited MU plitude.Automated envelope measurements do not exclude its dis
(#2) has a smaller amplitude than the first recruited MU (# I). In B, the charges as solitary spikes. By visual assessment, one may ignore thQ.~
later-recruited MU has a higher-amplitude MUAP. MUAP and the resulting envelope is indicated by the dashed line. This
amplitUde is reduced compared to normal.
When different MUAPs superimpose, the resulting signal can
have a higher amplitude than either component MUAP. Pitfalls. For EQUIP analysis, the IP parameters were devel
Computer simulations 128 (Fig. 8-46) indicate that this occurs rel oped based on recordings in the biceps brachii muscle and
atively rarely. The peak-to-peak deflection of the MUAP (i.e., its hence may not be suitable for other muscles. This is most likely
rise time) occurs in less than a millisecond. There is a very to be true in muscles in which activity values remain low de
narrow time window, less than a few hundred microseconds, spite a "full" pattern on visual inspection. As for the TA tech
during which two MUAPs must occur to summate construc nique, normal cloud limits must be developed for other muscles
tively. The chance of several MUAPs summating in this fashion in which the technique is to be applied. 30
is low. However, when this does occur, it is recognized as a soli
tary amplitude spike. As discussed earlier, these spikes are ex Decomposition
cluded from the envelope assessment. The envelope thus reflects Technique and Measurements. With digital signal process
the upper limit of amplitude of the MUAPs contained in the IP. ing, IP signals may be decomposed into the constituent
In myopathy, MUAPs may have a bimodal amplitude distrib MUAPs.122 The approach is similar to the earlier described
ution (Fig. 8-50). The high-amplitude MUAPs have a thin multi-MUAP analysis. However, this technique is more aggres
waveform, which distinguishes them from neuropathy. Because sive in identifying MU discharges and attempts to resolve
they occur frequently within the analysis epoch, the envelope MUAP superimpositions. Dorfman and coworkers 122 have used
amplitude measurement by automated methods may be normal. this approach for signals recorded at mild to moderate (30% of
They could potentially generate a data point that lies on the maximum) force levels. On average they could obtain 7 MUAPs
upper side of the normal "turns-amplitude" cloud. This should from each epoch of analysis.
not be misinterpreted as evidence of neuropathy and myopathy The reference values of features of MUAPs measured by this
in the tested muscle. When subjective assessment is performed, technique at different force levels are given in Table 10. 94
one may measure the envelope amplitude by excluding the dis MUAP duration values at threshold force are similar to those
charges of that single MUAP (Fig. 8-50). determined by other techniques described earlier (Tables 8-1-8-3).
From Howard JE. McGill KC. Dorfman LJ: Properties of motor unit action potentials recorded with concentric and monopolar needle electrodes:ADEMG Analysis.
o AHP (uU) 2K o
Figure '·51. ADEMG in a patient with primary lateral sclerosis. The data are presented as histograms. The shaded areas represent dis
tribution in normal subjects. In the patient, the ampliwde. duration and turns are relatively normal, but the MU firing rate is reduced. (From
Dorfman L. Howard J. McGill K: Clinical studies using automatic decomposition electromyography (ADEMG) in needle and surface EMG. In
Desmedt JE (ed): Computer-Aided Electromyography and Expert Systems. Clinical Neurophysiology Updates. Amsterdam, Elsevier, 1989. pp
189-204, with permission.)
The MUAP duration appears to be less at higher force levels. and myopathy. In patients with upper motor neuron lesions,
This is contrary to expectations that larger high-force threshold firing rates were reduced (Fig. 8-51),
MUs have longer duration. This probably results from the Clinical Interpretation. The analysis strategy is similar to
higher noise in the baseline of averaged MUAPs, which requires the MUAP analysis methods described earlier.
a much higher amplitude threshold to detect the MUAP onset Pitfalls. When several MUs are discharging, one may be
and end. The MU firing rate is increased at higher force levels, able to visually recognize 2-3 different MUAPs in the epoch.
as described earlier. The data also demonstrate the differences When the decomposition algorithm presents many more
in the MUAP feature values recorded by a concentric versus MUAPs, it is necessary to validate that individual MUAPs are
monopolar needle as discussed earlier. being measured. Validation of small-amplitude MUAPs can be
Clinical Findings. Although recorded at higher force levels, time-consuming. As with all other quantitative techniques, the
analysis involves measuring individual MUAP wavefonns. The reference values have been defined for only a few muscles.
reported abnonnalities are similar to those described in the Since this technique also records the higher force threshold
MUAP section. These investigators also analyzed the MU MUs, one may not use reference values from other MUAP
firing rate and found higher than nonnal rates in neuropathy analysis techniques.
a b
1'2~~--~~------------------~-, 100~~--------------------------~
1500
....•.••••••.••...•.•.. distance beI_n thl! muscll! fibTI! and electrode recording surface. 11m
Figure 8-52. Radial decline of the extracellular AP amplitude. Results of computer simulation for a single-fiber EMG (square), concentric
needle (diamond); and macro-EMG (triangle) electrode are shown. See text for details. (From Nandedkar S, Sanders D. Sdlberg E: Selectivity of
EMG recoprding electrodes. Med Bioi Eng Comput 1985;23:536-540, with permission.)
326 - PART II BASIC AND ADVANCED TECHNIQUES
•••
••
_~1·
••
- -II$,.
• ••
_..__._
'+ ~2~PV~
1 ms
...--'*o;;..... c
..• --.
. _Ue-"_ . _
IIOl.IOoO..
•• •• 2 • , : . .
~ 1~V
B
O.5ms o
:\
Figure '-54. FD and MU fiber distribution. Real fiber density signal recordings in B. C. and D are explained using a schematic MU cross-sec
tion in A. For SimpliCity, a single MU cross section is used. The recording positions I, 2 and 3 correspond to signals in B. C, and D. respectivelly.The
semicircle with a 300-lJm radius represents the uptake area of the electrode. The FD is recorded is I in B. and 2 in C. The small time-locked po
tentials indicated by the arrow do not fulfil the FD criterion and hence only 3 fibers are registered in D
Chapter 8 QUANTITATIVE EMG - 327
10 20 30 40 50 60 70 80
90
Frontalis 1.67 1.67 1.68 1.69 1.70 1.73 1.76
Tongue 1.78 1.78 1.78 1.78 1.78 1.79 1.79
SCM 1.89 1.89 1.90 1.92 1.96 2.01 2.08
Deltoid 1.56 1.56 1.57 1.57 1.58 1.59 1.60 1.62 1.65
Biceps Brachii 1.52 1.52 1.53 1.54 1.57 1.60 1.65 1.72 1.80
EDC 1.77 1.78 1.80 1.83 1.90 1.99 2.12 2.29 2.51
ADM 1.99 2.00 2.03 2.08 2.16 2.28 2.46
Quadriceps 1.93 1.94 1.96 1.99 2.05 2.14 2.26 2.43
Tibialis Anterior 1.94 1.94 1.96 1.98 2.02 2.07 2.15 2.26
Soleus 1.56 1.56 1.56 1.57 1.59 1.62 1.66 1.71
The upper normal limit for FD is tabulated for different age groups and in different muscles.The upper limit is higher in older subjects. SCM, Sternocleidomastoid;
From Bromberg M. Scott 0: Single fiber EMG reference values: Reformatted in tabular form. Muscle Nerve 19CJ.4; 17:820-821, with permission, and from Gilchrist J.
Barkhaus P: Single fiber EMG reference values:A collaborative effort. Muscle Nerve 1992; 15: 15 1-161, with permission.
of the AP of a muscle fiber that is just 300 Jim from the elec it is called a selective recording technique. Single-fiber EMG
trode may be less than 200 IlVYs When the display is adjusted provides a significant amount of physiologic information about
to accommodate the potential of the closest muscle fibers, sig just one or a few muscle fibers, but nothing about the rest of the
nals from the distant fibers of the MU are not recognized. The motor unit. Therefore, it is primarily suitable for studying focal
recorded MUAP may represent the AP of just one muscle fiber abnormalities of MU architecture.
of the MU, hence the name of this recording technique. Since The selectivity of the electrode can be increased further by
this electrode records from only a very small portion of the MU, increasing the low-frequency setting of the band pass filter.
A
Axon
_ _ _ _ _ _. ._ _ _ _ _ _ _ _ _ _ Muscle Fiber
Motor Neuron
• SFEMG Electrode
IDI •
..
B
100 ms'
c
D
O.Sms
-----..
O.Sms
Figure a·55. SFEMG jitter recording and analysis. In A. the electrode position is illustrated schematically. In B, the EMG signal is shown in
a free-running mode. The discharges of a single MU can be recognized quite easily at this slow sweep setting. The time interval between two MU
firings is the interdischarge interval (IDI). In C, a Signal-triggered delay line is used to freeze the signal for observation. The horizontal bar repre
sents the trigger level. In D, the triggered discharges are shown in a raster mode.The first potential triggers the sweep, thus appears time-locked
on the display. The second AP occurs at a variable interval. Furthermore, it did not occur in the sweep indicated by *, i.e., it blocked.
328 - PART II BASIC AND ADVANCED TECHNIQUES
Using a bipolar configuration of the recording electrodes also MU mkrophysiology. Since that time, SFEMG has become a
reduces the uptake area. 1 Such electrodes have been used for major tool in the electrodiagnosis of disorders of the neuromus
analysis of MU firing rate. cular junction. In conjunction with other recording techniques,
In macro-EMG, the recording surface is the cannula of a it has contributed to a better understanding of MU reorganiza
modified SFEMG needle. Because of the large recording sur tion in myopathy and neuropathy.
face, this electrode records with comparatively very low ampli The SFEMG signals are quantified mainly by measuring the
tude waveforms from single muscle fibers, even when they are fiber density (FD) and jitter. The latter measurement can be
close to the electrode surface (less than a few microvolts). The performed using volitional activity or by using electrical stimu
potential of distant muscle fibers is less attenuated than with lation. The recording and measurement techniques for FO and
other electrodes (Fig. 8-52). As a result, all muscle fibers, near jitter are quite different and are discussed separately.
and distant, contribute to the macro-EMG MUAP. Since the
electrode records from a large portion of the MU, macro-EMG Fiber Density
is called a nonselective recording technique. This technique is Technique and Measurements. In fiber density measure
useful to study global abnormalities of the MU, such as change ments (Fig. 8-54), signals are recorded as the patient exerts
in the MU size. minimal force of contraction from the tested muscle. The
Besides the large size of the recording surface, a technique sweep duration is usually 10-20 ms. The display gain is ad
can become nonselective by virtue of electrode placement. As justed to visualize the entire signal on the screen. The position
seen in Figure 8-52A, the AP amplitude decreases most rapidly of the needle is adjusted to maximize the amplitude and mini
at a short distance from the fiber. Away from the fiber, the de mize the rise time of a single-muscle-fiber AP. A signal-trig
cline is much slower and the differences between AP amplitudes gered delay line is used to "freeze" discharges of this potential
recorded by different electrodes become smaller. All muscle on the display screen. APs of other muscle fibers belonging to
fibers of an MU appear roughly equidistant to a remote record the same MU appear relatively time-locked on the screen. The
ing electrode. In this case, no single-muscle-fiber AP dominates number of such time-locked potentials that have an amplitude
the MUAP, which makes the technique nonselective. For exam greater than 200 IlV and a rise time less than 300 Ils is counted.
ple, the large distance between the MU and the large recording If two APs are partially superimposed, one may not be able to
surface makes surface EMG nonselective. assess their amplitudes and waveform. Nevertheless, it is rec
Special recording techniques provide complementary infor ognized by having a distinct notch in the rising or falling edge
mation about the MU architecture. We can obtain valuable infor of the potential. Such signals are also counted in FO measure
mation about the pathophysiology and disease progression by ments (Fig. 8-540). The process is repeated at 20 sites within
combining the results of several special recording techniques. the muscle. The average of these measurements is called the
fiber density (FO).
SINGLE-FIBER EMG Clinical Findings. The FD value is always greater than 1 by
virtue of the recording technique. In normal muscles, record
Still berg and Ekstedt developed the SFEMG technique in the ings from most sites contain just the triggering potential or two
early 1960s. Significant subsequent contributions have been time-locked potentials. This gives FO values between 1 and 2.
made by collaborations between Stillberg, Trontelj, and The upper limit of FD varies among different muscles. The limit
others. 191 SFEMG demonstrated that muscle fibers of a normal is also higher for older subjects, especially after the sixth decade
MU are scattered within the muscle. This was in contrast to the of life (Table 8-11).
concept that fibers of an MU are arranged in tightly packed FD values are increased in neuropathy and increase progres
groups, or subunits. This was a significant step in understanding sively when the disease progresses slowly.18.104,IJ 1.150,175.186.191.192.200
From Bromberg M, Scott D: Single fiber EMG reference values: Reformatted in tabular form. Muscle Nerve 1994; 17:820-821. with permission. and from Gilchrist J.
Barkhaus P: Single fiber EMG reference values: A collaborative effort. Muscle Nerve 1992; 15: 151-161, with permission.
In chronic neuropathies, one occasionally finds recording sites MCD =I IPI2 - IPI j I + I IPI3 IPI21 + ... + I IP~ -.IPIN _1 lIN -1
in which more than 10 muscle fibers are time-locked to the trig
gering potentiaL In these situations it may be difficult to count where N represents the number of discharges and IPIN is the
precisely the number of potentials that fulfill the criteria of rise inter-potential interval in the Nth discharge. At least 50 intervals
time and amplitude. The FO values are also increased in some should be analyzed to compute the MCD. The mean value of
types of myopathies. The highest values are usually seen in the IPI (MIPI) is also computed. Jitter measurements are best
Ouchenne muscular dystrophy, and other forms of myopathy performed when the MIPI is between 150 and 4,000 J.lS, for rea
show much less increase. This increase is explained by abnor sons discussed later.
mal fiber distribution in the dystrophic muscle (Fig. 8-55B). Sometimes the IPI is affected by the IDI from the previous
discharge (Fig. 8-55B), which makes it vary with the MU firing
Jitter rate. This would add jitter other than that due to neuromuscular
Technique and Measurements. transmission. To reduce the effect of firing rate variability on
Volitional Mode. For jitter measurements, the needle posi the jitter calculation, one may arrange the IPI values in the as
tion is adjusted to record APs from two (or more) muscle fibers cending (or descending) order of their corresponding preceding
in one MU (Fig. 8-55, A-B). The sweep duration is usually interdischarge intervals (lOIs). The jitter calculated on this or
5-20 ms. The display gain is adjusted as necessary. One muscle dered set of IPIs is called the mean sorted ditTerence (MSD).
fiber potential is used to trigger the sweep and the signal is de We use the smaller of the MCD or MSD values to represent the
layed for display (Fig. 8-55C). The triggering potential appears jitter in the pair of potentials.
time-locked and stationary on the screen. The electrode position When jitter is greatly increased, indicating a pronounced neu
is adjusted to find a position at which each of the individual romuscular disturbance, one fiber may fail to generate a poten
spike components fulfill the criteria of being generated by a tial with some MU discharges. This is seen when some
single muscle fiber. Unlike measurements of PD, this is not nec potentials are missing in some MU discharges (Fig. 8-55). This
essarily the position at which either of the APs is maximumal. If phenomenon is called blocking.
another potential appears relatively time-locked on the display, The jitter is measured from 20 different sites in the tested
it is in the same MU as the triggering AP (Fig. 8-550). Every muscle. Reference values have been defined for the mean jitter
effort should be made to make sure that only one MU triggers from 20 recordings and also for individual values (Table 8-12).
the sweep. When several MUs are active, jitter analysis can be A study is called abnormal when the mean jitter and/or more
quite tedious, time-consuming, and subject to errors. The time than 10% recordings exceed their corresponding upper limits.
interval between the two APs, called the interpotential inter The 10% limit corresponds to 2 abnormal recordings out of
val (IPI), varies from one discharge to another. This variability 20. It is quite possible that the third abnormal recording will
is the neuromuscular jitter is quantified by the following for be seen within the first few analyses.The test has reached di
mula, which calculates the mean ditTerence between consecu agnostic significance, and may be concluded at this point. If
tive potential intervals (MCD): the mean values are to be used to assess disease progression or
A IPI
MUtf.2 B
Stimulator
Cathode
c
eSFEMG Electrode
Figure 8-56. Stimulated SFfMG recordings. In A. the technique is indicated schematically. The cathode stimulates 2 different MU axons. The
electrode registers five different single muscle fiber APs. In B, signals recorded from one normal subject contain potentials from five different
muscle fibers. The jitter is normal. These APs belong to different MUs.
330 - PART II 'BASIC AND ADVANCED TECHNIQUES
.A _L GENERAL MUSCLE o
N Jitter Block MIPI
20 40 60 80 100
1oP'1<,nJ
Figure B-57. Automated analysis of jitter. Triggered sweeps recorded by an SFEMG electrode are shown in A. The H-shaped bars indicate
the windows placed on the signals to detectAP.The signals analyzed based on the window positions and after manual editing are shown in B.The
scatter of sequenctial interpotential intervals is shown in C (sweep number on X axis,lPI on Y axis).The gray rectangle defines a ± 3 standard de
viation band about the MIPI.The numerical data are presented in D.ln this recording, the jitter is normal.
the effect of treatment, jitter should be measured in 20 potential portion of the muscle, and its position and the stimulus intensity are
pairs. adjusted to record visually identifiable single-fiber APs. Instead of
The jitter varies slightly among different muscles and tends the intramuscular stimulation, one may use surface stimulation
to increase with age. The reference values used in our laborato technique to excite the tested nerve.63
ries for patients aged 20-60 years are summarized in Table 8 Jitter recordings are made at a stimulation rate of 10Hz,
12. Other muscles, such as laryngeal muscles, are now also which approximates the volitional MU discharge rate. It is im
investigated with SFEMG.16! portant to recognize that APs time-locked to the stimulus may
One can also measure the time interval between the first and belong to different MUs.
last time-locked AP in the signal. This is the maximum IPI for
that recording. The interspike interval (lSI) is computed as
maximum IPI I (number of potential time locked potentials - I).
This parameter is often increased in myopathies (Fig. 8-62), but
also in early reinnervation.
Stimulated Mode. Jitter can also be measured following stimu
lation.191,204,205,208 The sweep duration is usually 10-20 ms, but one
may need to increase this further to view and analyze potentials
with a longer latency. The display gain is adjusted as necessary. A
monopolar needle inserted proximal to the tested muscle stimulates
the intramuscular nerve fibers; a surface electrode is taped to the
skin nearby as an anode (Fig. 8-56). Very short stimulus pulses are
used (50 f.IS) with an initial rate of 1-3 Hz. The stimulus intensity is
gradually increased to produce a small twitch of the tested muscle.
The position of the stimulating electrode is adjusted to get the best
results. which usually occurs at 5-10 rnA. The stimulating needle
is then taped in place to maintain this position while the study is
performed. The SFEMG electrode is inserted into the twitching
A B SFEMG Electrode
,I./. .v
,v: .v
v:
v: y
y
V 1 ms
,V y 1ms
V v
Figure 8-60. Split muscle fiber. The schematic illustrates the split
in muscle fiber between the endplate and recording electrode. The
Figure 8-59. Jitter and blocking. In these stimulated SFEMG two time-locked action potentials shown below have very low jitter.
recordings, jitter is normal in A.ln B, the jitter is increased and a block This recording should be excluded from jitter analysis.
is seen on the fourth trace.
To compute jitter, the IPI is measured from the sweep onset or of these windows is adjusted manually to exclude other noise and
stimulus artifact (Fig. 8-56B). The MCD and MSO are computed interference. The window, indicated by a horizontal bar in Figure 8
as described earlier. In a typical study, jitter is measured from 30 57, is usually placed at the steepest rising portion of the AP. When
endplates. The data are analyzed from the individual jitter measure the potential crosses the bar, an AP is detected. When AP is detected
ments and also from their mean value. The reference values for in both windows, the IPI is measured. The systems allow the user to
stimulated mode are described in Table 8-13,205 Theoretically, the review individual sweeps to exclude traces that are noisy.
reference values for the stimulated jitter is the voluntary jitter IV2. When the IPI is small, it is difficult to position the windows
Many commercially available systems use two time-amplitude on the rising edge (Fig. 8-540). One may use the falling edge of
windows to detect a single-fiber potential (Fig. 8-52). The position the potential or its peak to measure IPI.
A
3 2 1
c
o
Figure 8-61. Jitter and discharge rate. Stimulated SFEMG recordings in a patient with myasthenia gravis when the stimulation rate is (A) 5 Hz,
(B) 10Hz, and (C,O) 20 Hz.The first spike at the beginning of the sweep is the stimulus artifact. This recording demonstrates rate dependent jitter,
velocity recovery function. (See text for details.)
JJ2 - PART II BASIC AND ADVANCED TECHNIQUES
Intracellular Potential
(mV)
1---·2
o
Threshold
-80
A
Time
Figure 8-63. Neurogenic jitter and blocking. The SFEMG record
ings (right) contain 6 differentAPs from one MU.The middle four poten figure 8-64. Genesis of jitter. The relationship between the end
tials shift and block together.A physiologic model (left) suggests a defect in plate potential and jitter is demonstrated schematically. A. Resting
nerve AP propagation at sites indicated by the arrow. The circle indicates membrane potential, B, Endplate potential, C. Action potential. (I)
the SFEMG electrode. (From Sdlberg EY, Trontelj JV: Single Fiber Normal jitter, (2) Increased jitter, (3) blocking. The gray area repre
Electromyography. OldWoking. UK, Mirvalle Press, 1979, with permission.) sents the threshold for generating AP.
Chapter 8 QUANTITATIVE EMG - 333
~
rectly stimulated by the intramuscular monopolar needle. Since
5m.
Figure 8-69. Stimulus intensity and jitter. In this stimulated SFEMG study, the intensity was increased gradually (from top to bottom).
Responses are shown in raster and superimposed mode. See text for details.
to reach the excitation threshold of the axon varies considerably amount of jitter as the recording is being made. Any discrepan
among successive stimuli. This variability increases the calcu cies between this subjective assessment and the results of auto
lated jitter. With some stimuli the axon may not be excited, mated measurements should be resolved before accepting the
which would be seen as blocking. Also, intermittent stimulation data.
failure produces a variable firing rate for the muscle fiber, which Whereas the FD can be measured on any instrument that
introduces artifactual jitter due to the velocity recovery func offers a trigger, delay line, and a band pass setting of 500--1 0000
tion, as previously described. To avoid this pitfall, the stimulus Hz, jitter analysis requires special equipment.
should be adjusted to assure that it is optimal for each AP to be Jitter with Routine EMG Electrodes. Attempts have been
measured.208 made to study the jitter in recordings performed with concentric
In Figure 8-69, the stimulus intensity was increased gradually or a monopolar needle electrodes. This may give values that are
(top to bottom). Initially (top set of superimposed traces), the po similar to those using an SFEMG electrode. 24,64.213 However, it is
tential shows a high jitter and long latency. At higher intensity important to recognize that the eN and MN electrodes have a
(second set), the latency and jitter are reduced. In the third set re much larger uptake area. Thus, the spike component of their
cruitment of more fibers is seen, which have high jitter and MUAP is the summation of several muscle fiber APs. What ap
blocking. Increasing intensity (fourth set) reduced their jitter and pears as a single spike may not necessarily be a single muscle
there is no block. These potentials have adequate stimulation and fiber potential, but a superimposition of two or more potentials.
they can be used for jitter analysis. Another fiber is seen near the This may lead to an underestimation of the jitter. Similarly, it is
end of sweep. It has high jitter and blocking due to suboptimal not possible to measure FD with these electrodes, since their
intensity and it should not be analyzed. In the last set, the in recording surfaces are too large to resolve the MUAP into its
crease in intensity stabilizes the last potential and can be used for component APs. Therefore, we prefer to make these measure
jitter measurements. However, jitter analysis is difficult for po ments using the SFEMG needle only.
tentials in the center of the sweep where jitter appears increased
due to suboptimal stimulation of the newly recruited fibers. Relevance to Routine EMG Studies
In stimulated SFEMG, some fibers may be excited when the SFEMG is a very sensitive procedure. It demonstrates in
stimulation rate is increased (Fig. 8-61, potential 1). Their po creased FD before fiber type grouping is seen on muscle
tentials may have high jitter and blocking similar to suboptimal biopsy.90 In disorders of neuromuscular transmission, increased
stimulation described earlier. jitter is seen even when there is no weakness or decrement to
The SFEMG electrode is quite expensive and requires care repetitive nerve stimulation in the tested muscle. 82 However, in
and maintenance. Without attention, the electrode impedance creased jitter and/or FD are seen in a number of neuromuscular
may become so high that it may not be possible to get good diseases, making SFEMG diagnostically nonspecific. The re
recordings from the needle. The tip of the needle must be kept sults from SFEMG testing should be interpreted in light of in
sharp to reduce discomfort and to avoid trauma to the muscle formation from the patient history, routine EMG, and nerve
fibers during recording. conduction studies. On the other hand, because of its sensitivity,
SFEMG recording is an art that is mastered only after weeks we can say that weakness in a muscle in which jitter is normal
or months of practice. Analysis of traces can be time-consuming cannot be due to abnormal neuromuscular transmission.
when the recording contains discharges of more than one MU. Increased FD is the earliest electrodiagnostic abnormality in
It is quite frustrating to spend an hour with the patient and a reinnervated muscle. Thus, increased FD measurements can
obtain only a few pairs for jitter analysis. There may not be suf be used to demonstrate neurogenic involvement in muscles in
ficient reimbursement for the amount of time spent on analysis. which reinnervation has prevented development of weakness.
Reliance on automated measurements accounts for many of This may help in the study of motor neuron diseases, where
the errors in SFEMG analysis. The operator should be suffi neuropathic abnormalities must be demonstrated in several
ciently experienced to identify blocking, and to estimate the muscle groups.
336 - PART II BASIC AND ADVANCED TECHNIQUES
o
t
2
.----- .. , ~.
I
80
o
.... 70
I..-J~--.
60
SO Myopathy
~--,_--_r---,----r_--,_--_r--~~--~--~20
1200
c-
Jitter
-0- an. MG - - JltUr IM..n MCDI
Figure 8-11. The relationship between FD. jitter, and disease
Figure 8-10. Serial jitter studies. Serial measurements of jitter in progression. The shaded area indicates normal findings. See text for
a pregnant woman shows a concommitant change in jitter (bottom details. (From Sdlberg EY.Trontelj JV: Single Fiber Electromyography.
trace) with disease severity (top trace). (From Massey JM. Sanders DB: Old Woking. UK. Mirvalle Press. 1979. with permission.)
Single fiber electromyography in myasthenia gravis during pregnancy.
Muscle Nerve 1993; 16:458-460, with permission.)
Serial SFEMG studies may be helpful in assessing the response
to treatment, and will usually continue to show abnormal jitter
Serial FD measurements are also useful to demonstrate MU after RNS become normal. The biggest advantage to jitter mea
remodeling after nerve injury."4.199 During reinnervation, jitter surements is in the suspected MG patient with normal RNS test
and blocking are increased in newly formed endplates. This ing. Because of its great sensitivity, SFEMG demonstrates
electrophysiologic observation indicates that MU remodeling increased jitter in some muscles in virtually all patients with
has not reached its maximum and thus further improvement is MG.157 Thus, normal jitter values in appropriately tested mus
possible. When reinnervation is complete and the newly formed cles can be very helpful in excluding the disease. If jitter is
endplates are mature. the jitter returns to normal. This indicates normal in a weak muscle. the weakness is not due to abnormal
a status quo that may not be a good prognostic sign for patients neuromuscular transmission.
recovering from nerve injury. The combination of jitter and FD gives information about dis
In patients with neuromuscular junction disorders. jitter cor ease progression in patients with neurogenic diseases. In a
relates with the disease activity. When the disease is in remis slowly progressing neuropathy the FD increases significantly
sion, jitter becomes less, and may even become normal in some while the jitter remains relatively normal (Fig. 8-71, top left).
muscles. Thus, jitter measurements can be used to assess the The slow progression allows the MU to complete reinnervation.
effect of treatment (Fig. 8_70).95,113.115.154.157 SFEMG is also This increases the MU size and hence the FD. This combination
useful in assessment of botulism.36.m of findings can also indicate an old MU insult.150.155.212 In con
When repetitive nerve stimulation (RNS) demonstrates a trast, a slightly increased FD with significantly increased jitter
decrement. SFEMG may not add much to electrodiagnosis. in a weak muscle indicates an active disease process with more
~50~V :
1 ms
Chapter 8 QUANTITATIVE EMG - 337
rapid progression (Fig. 8-71, bottom right). If both FD and jitter Normal
are increased (Fig. 8-71, top right), this indicates acceleration or
recent onset of a slow disease process. 186.187
As described earlier, raising the low-frequency setting of the
band pass filter to 500 Hz attenuates signals from distant fibers.
Such a filter setting in the routine EMG recordings enhances
any irregularities in the signal. The effect is similar to remov
ing a blanket over a statue when it is unveiled. This concept is
called the blanket principle (Fig. 8_72).143 Also, this reduces
the MUAP amplitude and duration, making them appear "myo
pathic." A smooth MUAP waveform may be transformed into a 1100J.lV
signal with several peaks representing signals from individual
muscle fiber. In normal MUs, the MUAP waveform remains CAD = 0.009
relatively constant during successive discharges. This is called CCC = 0.989
a stable MUAP. When the waveform varies significantly from
one discharge to the next, the MUAP is called unstable (Figs. ALS
8-6 and 8-72). These changes in the MUAP waveform repre
sent increased jitter and blocking of the muscle fiber potentials
contributing to the MUAP, the same phenomena that can be
seen more precisely with SFEMG. After assessing MUAP sta
bility, the filter values should be returned to the default set
tings, otherwise the signals will appear to have reduced
amplitude and duration. '.
'I
When MUAPs appear unstable by visual assessment,
SFEMG also shows increased jitter and blocking. However, I
jitter as seen on SFEMG may be masked when the jittering po 11mV
tential is superimposed on normal fiber potentials. Also, as dis
cussed above, several fibers may contribute to the APs seen with CAD = 0.770
MN and CN electrodes, and it may not be valid to measure their CCC = 0.677
time variability as in SFEMG. As described previously, the
CNEMG or monopolar EMG, even with filtering, cannot be Figure 8-73. Jiggle. In the top recording, the MUAP waveform has
used to quantify the FD values. minimal variability and a jiggle of 0.009. For the recording in a patient
Stalberg and Sonoo l89 have proposed an alternative parame with ALS (bottom), the variation in waveform is obvious. The jiggle is
ter, called jiggle, to measure this instability of the entire MUAP 0.77. (From Sdlberg E,Sonoo M:Assessment of variability in the shape
waveform (Fig. 8-73). A 2.5-msec epoch centered on the peak of the motor unit action potential, the "jiggle" at consecutive dis
of the MUAP is selected for analysis. This contains mainly the charges.Muscle Nerve 1994;17:1 135-1 144, with permission.)
spike component of the MUAP. The amplitude change in suc
cessive discharges of the MUAP at each MUAP sample point is digitization, as seen in the bottom traces of Figure 8-75. This is
measured. The median value of this measurement is computed. more likely to occur at the most rapidly changing portion of the
The area under the waveform generated by connecting these signals, i.e., at the peak of the waveforms with a low rise time.
median values is divided by the area of the averaged MUAP to
quantify the jiggle, called consecutive amplitude difference
(CAD).
In some MUAPs, the instability is recognized by the variabil
ity of MUAP amplitude. This is seen easily at a slow sweep A Ir L J
speed (Fig. 8-74). This was one of the earliest EMG abnormali I· ~.
1 mV .
ties described in patients with MG.86 However, on some digital 100ms
electromyographs, amplitude variability may also be seen in
very sharp normal MUAPs. This occurs from so-called aliasing,
an artifact of digital signal processing, produced as described
below.
A digital instrument measures the instantaneous voltage of
EMG signals at regular time intervals (Fig. 8-75). Each mea
surement is called a sample and the time between successive B
samples is the sampling interval. The reciprocal value of the
sampling interval is the sampling rate. The samples are then
plotted in the same sequence as on acquisition, and are con
nected with straight lines. The resulting waveform is the digital
representation of the signal. In Figure 8-75, there is a good
match between the digitized signal and the analog waveform in Figure 8-74. Jiggle. In A, one second EMG recording from a patient
the top trace. If the sampling rate is reduced, the system may with neuropathy shows significant variability in its peak to peak ampli
fail to acquire adequate samples from the rapidly changing tude. Using a triggered delay line (8) and a faster sweep confirms the
components. This gives a distorted view of the EMG signal after variability of the MUAP waveform (C).
338 - PART /I BASIC AND ADVANCED TECHNIQUES
......
-----.,....~
aliasing errors, use faster sweeps (e.g., 2-3 ms/div) and an am
plitude trigger delay line to assess the stability. On many sys
tems, the indicated change in sweep speed increases the
sampling rate and thus reduces aliasing.
Figure 8-75. Analog to digital converison.This concept is illus SURFACE EMG AND MU NUMBER ESTIMATION
trated schematically. In solid line indicates the analog signal.The circles
are individual sample points. The sampling rate is reduced by 50% in Surface EMG recordings are routinely performed as part of the
the bottom trace.The digital signal indicated by dotted line is quite dif nerve conduction studies. The compound muscle action potential
ferent from the analog signal. (CMAP) amplitude is assessed for abnormalities of conduction., e.g.,
conduction block, and also for muscle wasting and atrophy.
Additionally, surface EMG recordings offer a noninvasive method
The peak of the MUAP appears variably among different dis of studying muscle fatigue. Multichannel recordings are useful for
charges and looks like a MUAP with varying amplitude. assessing movement disorders and characterizing tremor. Other
This problem can be resolved by increasing the sampling than the nerve conduction studies, surface EMG recordings are not
rate. The Nyquist theorem specifies that the sampling rate used in routine electrodiagnostic medicine evaluation. There is a
should be at least twice the maximum frequency in the signal. 99 great deal ofinterest in developing techniques to monitor and follow
The maximum frequency in needle EMG recordings is at least disease progression using surface recordings of EMG signals.
10 kHz. Thus the sampling rate should be at least 20 kHz, One such application of surface EMG is the technique of
preferably more than 40 kHz. If the instrument cannot support motor unit number estimation (MUNE), also known as motor
A
~~·U· ~~.~ ,,~, t··
B
~·+j"I··~, ·W
c
+~t· f .~ i· l+·t··f· t
Sweep Duration = 1 second
Figure B-77. MU depth and SMUAP amplitude. SMUAPs
recorded at minimal force of contraction from the biceps brachii
Rgure 8-76. Aliasing or jiggle? In A,a normal EMG signal containing a muscle of a normal subject as described in Figure 8-83. When the in
sharp MUAP was sampled at 50 kHz. In B. the same signal was sampled at tramuscular triggering needle tip was within 10 mm of skin surface.
3 kHz, and shows amplitude variability due to aliasing. In C, the recording the MU was identified as being superficial. Similarly, when the tip was
from a patient shows amplitude variability.This is seen when the sampling more than 20 mm from the skin surface, the MU was considered deep.
rate is 50 kHz and hence it is not a technical artifact. Without knowing the Observe the differences in the SMUAP amplitude for these MU
sampling rate. we cannot tell if this reflects pathology or aliasing. (from groups. (From Barkhaus PE. Nandedkar SO: Recording characteristics
Barkhaus PE. Nandedkar SO: In Nandedkar SO (ed): EMG on CD. CASA of the surface EMG electrodes. Muscle Nerve 1994; 17; 1317-1323,
Engineering. Hopewell Junction,Volume II, 1999, with permission.) with permission.)
Chapter 8 QUANTITATIVE EMG - 339
unit counting. Loss of MUs is an important disease process in When the skin and subcutaneous tissue is thick, the distance
patients with neuropathy. Information about the number of MU s between the electrode and the MU is increased. This yields a
in a tested muscle would be very useful in assessing the severity smaller amplitude for the SMUAPs and the corresponding
and progression of the disease process. CMAP (Fig. 8-78A). Changes in skin and subcutaneous tissue
thickness, e.g., after weight loss or gain, also affect surface
Recording Characteristics of Surface EMG Electrodes EMG measurements.
Because of its placement, the surface electrode is roughly In normal subjects there is no direct correlation between the
equidistant from all fibers in the MU. Hence all muscle fibers biceps brachii muscle strength and its CMAP amplitude (Fig. 8
contribute similarly to the surface-recorded MUAP (SMUAP), 78B). This is expected since the uptake area of the IO-mm disc is
making this a relatively nonselective recording technique. The not large enough to record from the entire biceps brachii muscle.
SMUAP amplitude and area should reflect the MU size. The electrode records from roughly the same number of genera
However, if two MUs of the same size are located at different tors among different subjects, regardless of total muscle bulk.
depths from surface, the deeper MU, being farther from the elec In patients, one can use the CMAP for the tested muscle as a
trode, has a smaller MUAP (Fig. 8-77). Barkhaus and Nandedkafl "reference" value. Changes in CMAP size reflect the progres
estimate that the 100mm disc electrode used in nerve conduction sion of certain diseases. In myopathy, they reflect mainly the
studies records mainly from muscle fibers that lie within 2 em of loss of individual muscle fibers within MUs and their atrophy.
the electrode. This recording territory is large enough to contain In neuropathy, the reduced CMAP results mainly from the loss
most muscle fibers in the small distal muscles used in nerve con of MUs. Hypertrophy of muscle fibers results in a higher
duction studies, e.g., APB, ADM, and EDB. However, this CMAP amplitude.
recording territory contains only a moderate portion of the large
limb muscles, such as the biceps brachii. To record from such MUNE Technique
muscles one should use a recording strip oriented perpendicular MUNE is a three-step process. First, the CMAP is recorded
to muscle fibers, which covers most of the muscle. Such special from the tested muscle using standard nerve conduction tech
electrodes have been used in MUNE techniques. niques. The CMAP is the sum of the SMUAPs of all MUs in the
muscle. Hence the amplitude (or the area) of the CMAP repre
(A) CMAP vs Skin Thickness sents the "electrical size" of the whole muscle. In the second
step, the electrical size of individual MUs is estimated by direct
CMAP(mV)
25.0
or indirect assessment of their individual SMUAP amplitude (or
area). Techniques that have been developed for this assessment
13
• will be discussed shortly. Finally, the CMAP amplitude (or
• 23.548
• -e.1I54 • area) is divided by the average SMUAP amplitude (or area) to
r -e.1I12
"" 1._ • estimate the number of MUs in the tested muscle, by the follow
t -5.921
...r 11 ing formula:
MUNE =CMAP amplitude (or area) I average SMUAP ampli
• • tude (or area)
We review the technique and pitfalls of different methods
used to estimate the SMUAPs and their amplitude.
0.0
0,0 SKIN_THIO< (mm) 2(10
(8) CMAP vs Resistance
CMAP(mV)
25.0
•
•
•
•
•
• •
'n
• • .~
•
~100:IJV :
2ms
0.0
0.0 RESISTANCE (Kg) 30.0
A B Fig. 8-80). When these criteria are met, the signal is considered
to be an SMUAP. We will call this response "step I."
After establishing the first MUAP, the intensity is increased
50
further. The response remains unaffected by the intensity until
the second axon is stimulated. Once again, slight changes in the
51
intensity reveal only three distinct waveforms: baseline (step 0),
the first SMUAP (step 1), and the third signal, which is consid
52
ered to be the sum oftwo SMUAPs (step 2) (Fig. 8-80, response
S2). Since no intermediate configurations of the waveform are
53 recorded, this is a stepwise change. The process can be repeated
to get additional steps in the response, resulting from the pro
gressive stimulation of additional axons (Fig. 8-80, responses
S4
S3 and S4). Dividing the final response amplitude by the
number of steps (i.e., the number of MUs) gives the average
c SMUAP amplitude. This value is used to calculate the MUNE.
Each incremental step theoretically represents stimulation of
Figure 8-S0. Incremental stimulation technique. The motor one additional axon. Individual SMUAP waveforms can be ob
nerve conduction program was used to record evoked responses tained by subtracting the waveforms produced at successive
from the APB muscle as the median nerve was stimulated at the wrist. step. For example. subtracting step 0 from step I gives the
A stepwise change in the response was observed as the stimulus in SMUAP of the first stimulated MU. Subtracting step 1 from
tensity was gradually increased. In A, two trials of each step are shown step 2 gives the SMUAP of the second stimulated axon, and so
superimposed. The average of these two trials from each step is shown on (Fig. 8-81). It is interesting to note that the amplitude of the
in superimposed fashion in B. Note the very slight change between summated SMUAPs (Trace S4 in Figure 8-81A) thus obtained
the responses when the intensity was increased. The peak-to-peak am is smaller than the sum of amplitudes of the individual
plitude at step 4 was 177 !-IV, which gives mean SMUAP amplitude of SMUAPs (Traces MI-M4 in Figure 8-81-B). This results from
41.25 ",v. In C, the CMAP at supramaximal stimulation has peak-to the phase cancellation among individual SMUAPs as they are
peak amplitude of 13.6 mV.This gives an MU count of 307. summated. Some describe this as "lack of algebraic summation
of SMUAP amplitude in the CMAP." Using the algebraic mean
Incremental Stimulation. McComas and coworkers76,117.ll9.120 of SMUAP amplitude rather than the sum will give a smaller es
pioneered MUNE by describing the technique of incl'emental timate of the MU count,47
stimulation. In this method, the surface EMG is recorded in re Although the incremental stimulation method is conceptually
sponse to nerve stimulation as the stimulus intensity is gradu simple, it is technically quite demanding. The changes in the re
ally increased. Initially, the intensity is too low to stimulate any sponse may be so small that they are not easily detected. This is
nerve fibers and the signal contains no MU activity (Fig. 8-79). more likely to occur when MU size is reduced, as in myopathy.
We will refer to this signal as "step 0" (response SO in Fig. 8 Failure to recognize small SMUAPs gives an incorrectly higher
80) and used it as the baseline. The intensity is increased until calculation of SMUAP amplitude, producing a lower MU count. 142
the EMG contains a waveform that is time-locked to the stimu Ifaxons A and B have very similar stimulation thresholds, we
lus and appears in an all-or-none fashion as the stimulus inten can observe so-called alternation in responses. Sometimes we
sity is slightly reduced or increased (Fig. 8-79, response S 1 in will record SMUAP from axon A, sometimes from axon B, and
A B
A B
50 ~----'--I M1
51
_____- - - 1 M2
52
- M3
.~:
53
2m•
S4 .~. ..~M4
[:IOO.,v :
. L-.J
2mo
A
A B
, R9IC€PS ' RSICEPS
8 ~
I-~-:
c ., ... ~
-I
... .:v~'
. .
..
2O ...V
..
~
~10jlV
.,
Sma . SInS
90
..... u .. "~ ..........n ...... _ ....................................... _ ..... _ ••
:4
III
•c
eo o
II
II
~ .... _•• n ••••••••• _.•_••••• _ ••_.n.u._H .. _n......."'.~_ ..
H' ..... 1 •
7D :3 n
._H.·._·U.... ..........___.__._.....
~
: d
n . _ ..... _
. . . . . . . . . ~ ••u
........... j •
50 :2 t
._...._...............u.u_._....__ ._............................_.; i
n
9
,
a
N level I SKP uV lIME 30 n
11
'.m....................................· ..·•.. •·• ..•..•..·..·, •
•
2 2D
._H........... H"'.n.n............. _____._......• ••• ... __··_·_·_··
!1
3
10
4
D.j-,..,"T"T'T'T"t"""""""'T'T"""""TT1rTTT"T"l"TTTT'1 Cu r ve
o 10 20 30
Figure 8-87. Evoked response amplitude versus stimulus intensiry in a patient with ALS.The evoked responses (top left) in the EDB
muscle of a patient with ALS show a stepwise change in the area (right) Four ranges for MUNE are indicated by the dashed rectangles. Note the
large step size when the area changed from roughly 60% to 80% of maximum by a minimal increase in stimulus intensity. The range used for test
ing falls at the center of such a step. (Courtesy Dr. B. Smith. Scottsdale.AZ).
Level:
St im:
10
m~It'++'flILYfIAAIf-IllWt'flrLfJhr-r-rn Ar ••
55 60 65 70 75 eo "
Figure B-88. MU estimation by the statisticaJ method. Refer to text for details. (Courtesy Dr. B. Smith. Scottsdale.AZ).
Findings in Normal Subjects and Patients to monitor changes in the CMAP size. This is certainly useful in
Using the incremental stimulation technique, McComas and the acute phase. If reinnervation is unsuccessful, as in a rapidly
coworkers found a loss of MUs in older subjects.16.117-121 This progressive neuropathy, the CMAP should also be useful to
was attributed to the normal aging process. In neuropathy, the monitor MU loss. In a slowly progressing neuropathy, reinnerva
MU count was reduced as expected. Those investigators also tion may be able to compensate for loss of MUs. This gives a
found a reduced MU count in dystrophy. This formed the basis normal CMAP size despite a reduced MU count. It is in such
for a "neurogenic hypothesis" for dystrophy.1I8 It was demon conditions that the MUNE could be of greater utility than CMAP
strated that the incremental stimulation method might miss amplitude measurements in assessing disease progression.
some small-amplitude SMUAPs. This gives higher amplitudes It is important to remember that a change in the skin and sub
for individual SMUAPs and thus a reduced MU count in dystro cutaneous tissue thickness between successive studies also af
phy, which could be interpreted as neurogenic changes. fects the CMAP measurements. When recording the CMAP,
In the last two decades, the different techniques have been neighboring muscles are also activated. The CMAP contains the
used to study other normal muscles.119.166 The findings of some volume-conducted activity of these muscles. In contrast, indi
studies are summarized in Table 8-15. All techniques have vidual MUAPs can be limited to the tested muscle. Thus, MU
demonstrated changes consistent with loss of MUs in normal counts may give overestimates. While all axons will be stimu
older subjects and in patients with neuropathy. The diagnostic lated in normal subjects, demyelinated axons may require much
sensitivity of these technique has not been compared rigorously higher intensity. If these axons are not stimulated, a smaller
with other EMO parameters such as FD. CMAP and a lower MU count are obtained.
Clinical Interpretation. It is obvious that MU counting tech MU loss can also be observed, though not quantified, with
niques are still in a developmental stage. The techniques can be other procedures. Changes in the F-wave morphology reflect re
time-consuming, tedious, susceptible to errors, and require spe organization of MU architecture due to disease processes. When
cialized hardware and software. Furthermore, the diagnostic sen MUs are large due to reinnervation, F-waves may become com
sitivity of this method has not been compared with other routine plex and have high amplitude. This change can also occur if the
test procedures. In many instances, the lower normal limit is less excitability of the motor neurons is increased so that F-waves
than half the mean value (see Table 8-15). This means that up to are generated in more MUs.
50% of MUs could be lost without reducing the MUNE below In nerve conduction studies, the probability that a given MU
normal limits. Despite these limitations, these techniques may be will generate an F-wave is small. However, because a large
useful in assessing disease progression in individual patients. number of MUs participate in the response there is a good
The MU count depends directly on the size of the CMAP. In chance that at least one of them will generate an F-wave at
patients with neuropathy, a simple way to follow the MU loss is supramaximal stimulation. In normal subjects, most stimuli
346 - PART II BASIC AND ADVANCED TECHNIQUES
generate an F-wave. When the number of MUs is reduced, it be MUNE and Disease Progression
comes more likely that none of them will generate an F-wave. Despite all of the limitations and differences among different
This is seen as a reduced percentage of F-responses. It is neces methods, the MUNE is a parameter of great value in assessment
sary to deliver a large number of stimuli to demonstrate this re of progressive degenerative diseases, e.g., amyotrophic lateral
duction. If the excitability of the neurons is reduced, the F-wave sclerosis (ALS).22 Many studies have demonstrated changes in
persistence (i.e., percentage of responses with F-waves when a CMAP, MUNE, grip strength, macro-EMG, and fiber density
large number of stimuli are delivered) also decreases. with disease progression.5,6,2o,7o,22o Among different studies, the
Loss of MU is also reflected by presence of spontaneous ac MUNE was found to be most suitable in quantifying disease
tivity, abnormal waveform of MUAPs, and incomplete or dis progression. Yuen and Olney220 also found fiber density changes
crete IP at maximal effort. useful when the disease progression was relatively slow. Yet
there is a lot still to accomplish, e,g" the intrasubject variability
needs to be reduced, Fortunately, all techniques demonstrate
greater reproducibility when the MU count is reduced, i.e., in
pathologic situations. In normal subjects, the estimates have
much higher variability.5,I9,69,llO,I4I,I68 As many methods are
available only as proprietary software, there may be method
ologic differences that are not adequately described that may
cause further confusion. Nevertheless, this is an exciting devel
opment in the electrodiagnostic techniques.
A
MACRO·EMG
Recognizing the dependence of SMUAP amplitude on the
MU location within the muscle, Stalberg lSO developed the tech
nique of macro-EMG to assess the MU size.
Technique and Measurements. The recording electrode is a
modified SFEMG needle, with a cannula insulated except for the
distal 15 mm. The active recording port of the SFEMG electrode
B SFEMG 4--------~------
A B C
C caNlula~~l100"V
10ms
-----~
---~
----~~
~---
---J'"'o-- ---"----
--...J'\- - r " - -
- - - J ' - ----./'0--
~---f'..--
!:::
--...J\-..-.- ~
-Jv-~
~--1100"V
~-----A--
D A......aged response
-~-~
ImacroMUPI
~----fL--- ---..J'-- ..--JI..
~---------
10ms
=j:=1\;
-J'-~ __
--oJ'- - .J\...
Figure 8-90. Macro-EMG.A schematic cross section of a MU with ---..r----- ~-- - - I ' - ----"--
a macro EMG electrode superimposed, and the recording montage ~--"--- ---J'---- - - - " - - ~~
(A). Note that the cannula passes through the MU territory. SFEMG
signals are shown in free-running mode (B). The discharges of a Single
~~----
--..A-..- -----"-- -J\- --J:::JSOOtl'
:10...
MU are easily recognized. In C the macro-EMG signals are shown. The
macro-MUAP (D) can be recognized in C. (From Sdlberg E: Macro Figure 8-9'. Macro·EMG MUAPs. Recordings from the biceps
EMG, a new recording technique. J Neurol Neurosurg Psychiatry brachii muscle of (A) patient with myopathy, (B) normal subject, and
1980;43:475--482, with permission.) (C) patient with neuropathy are shown.
Chapter 8 QUANTITATIVE EMG - 347
______.____ ~A-___________________ ___ 1
exits at the center of the bare distal shaft opposite the bevel. Two
channels of EMG activity are recorded (Fig. 8-90A). SFEMG sig
nals are recorded on the first channel as described earlier. For the
second channel, the cannula is used as the active recording surface
and a remote surface or monopolar needle is used as reference.
A
The SFEMG signal is used to identify individual MU activity (Fig.
8-9OB). This is used to trigger the sweep and the averager. The sig
nals from the second channel (Fig. 8-9OC) are delayed and aver
aged to extract the macro-EMG MUAP (Fig. 8-900).
Twenty or more MUAPs are recorded from different sites in 2
the tested muscle. The shape of the Macro MUAP remains rela
tively constant even when the needle position changes within
the MU territory. Thus, duplicate recordings can be identified
and excluded from analysis. For each MUAP, the amplitude and
area under the rectified waveform are measured. Due to the
skewed distribution of these parameters, the median instead of 1
mean value is used as the measure of central tendency. Normal
values are defined for the upper and lower limits of the median
as well as individual MUAP measurements. 1500 pv
Findings in Normal Subjects and Patients. In normal sub B
jects the MUAP amplitude increases with age, especially after ~ 300 p-v
the sixth decade. The limits vary among different normal mus
cles (Table 8-16). 2
In neuropathy, the macro-MUAP amplitude is increased (Fig.
8-91). Serial studies demonstrate a reduction in amplitude when
the muscle becomes severely weak (Fig. 8-95, 8-96). In myopa
thy, the macro-MUAP amplitude is normal or reduced (Fig. 8
91, 8-98). Serial studies demonstrate progressively reduced
amplitude as the weakness progresses. Figure 8-92. Conmac recordings from patients. A. Patient with
Interpretation. The macro-EMG active recording surface is myopathy; B, patient with neuropathy. For both patients, trace I is conmac
large compared to eN and MN electrode recording surfaces, potential, trace 2 is the routine concentric MUAP.The calibrations for the
making it nonselective. Thus, when the position of the electrode two patients are indicated separately. (From Gan R,Jabre jF:The spectrum
changes, the MUAP waveform remains relatively constant. This of concentric macro correlations. Part II. Patients with diseases of muscle
has been demonstrated by computer simulations l26 and also by and nerve. Muscle Nerve 1992;1 5: 108S-1 088, with permission.)
experimental recordings. 18o The macro-MUAP of high-force
threshold MUs has larger amplitudes than low-force threshold or only slightly reduced macro-MUAP size (Fig. 8-91, 8-98).
MUS.98,181 This also demonstrates that the macro-MUAP reflects These compensatory processes will also be manifest as an in
the MU size, By virtue of its construction, the electrode passes creased FD on SFEMG.92 In inclusion body myositis, serial
through most of the MU territory (Fig. 8-90). It is close to the studies demonstrate reduced macro-MUAP amplitudes as weak
muscle fibers of the MU. Therefore, the macro-MUAP stays rel ness progresses. This reflects progressive loss of muscle fibers
atively constant at different recording positions. In contrast, the and changes in fiber size (Barkhaus, personal communication).
surface MUAP depends on the MU position from the skin sur
face as well as thickness of the skin. Therefore, the macro
MUAP is a better estimator of MU size than the surface MUAP.
In neuropathy, the macro-MUAP is larger than in controls, in
dicating increased MU size due to reinnervation (Fig. 8-91).
The highest values of amplitude are recorded in patients with
slowly progressing disease where reinnervation can compensate A
The Conmac Electrode. Macro-EMG is the only technique PUTTING IT TOGETHER: QUANTITATIVE
that truly gives information about the MU size. In some condi ANALYSIS AND A MODEL FOR DISEASE
tions, other EMG techniques may demonstrate mixed features. PROCESSES
In such cases, macro-EMG could be useful in demonstrating
changes in MU size. The macro-EMG electrode is rather expen So far we have looked at the quantitative techniques and fo
sive, it is not disposable, and requires special care and mainte cused on information each provides about specific aspects of
nance as well as experience with the technique.
Iabre 96•97 developed a two-channel recording technique to
measure signals similar to the macro-EMG with a CN electrode.
The first channel records the CN EMG signals between the cen
tral wire and the cannula. The second channel records the activ
ity from the cannula with reference to a remote reference
electrode. Because the cannulas are similar in size. these record
ings give similar information to macro-EMG (Fig. 8-92), hence
the name conmac for the technique. In Figure 8-92. concentric
and conmac recordings from two different MUs are shown. 77
The top two traces are from a patient with myopathy, the bottom
traces from a patient with neuropathy. The concentric needle
recordings (A2 and B2) have complex waveform with long du
ration, satellite components, etc. This is a nonspecific finding
and cannot differentiate between a myopathy and neuropathy.
However, the conmac signal shows very low amplitude for my
opathy (trace A I) and increased amplitude in neuropathy (trace
B I). Thus, conmac is able to differentiate pathology when the
conventional recordings demonstrate nonspecific findings.
If the needle passes through the MU, the cannula is inside the
MU territory as in macro-EMG, and the macro and conmac
MUAPs should be similar (Fig. 8-90A, 8-93A). However, if the
needle tip is at the edge of the MU territory, the entire cannula is
outside the MU territory (Fig. 8-93B). This gives a low-amplitude
cannula potential. Due to these differences, one expects a slight
difference between the amplitudes of macro-EMG potentials and
the conmac recordings. 140 A reduced conmac MUAP may not
necessarily come from a small MU. The probability of such elec
trode placement (Fig. 8-93l3) is expected to be small. On the Figure 8-95. Quantitative EMG in polio. The relative change in
other hand, increased conmac MUAP amplitude would be consis nFD, and CN MUAp, and macro-MUAP amplitude in muscles with dif
tent with increased MU size regardless of the electrode position. ferent degrees of weakness from old polio is shown. (From Sanders
Macro-EMG and MU Number Estimation. Since the DB, Massey JM, et al: Quantitative electromyography after po
macro-MUAP amplitude reflects the MU size, it can be used to liomyelitis.ln Halstead LS,Wiechers DO (eds): Research and Clinical
assess loss of MUs and reinnervation. If the macro-MUAP am Aspects of the Late Effects of Poliomyelitis. Birth Defects: Original
plitude doubles, it would imply that 50% of MUs have been lost Article Series, March of Dimes. White Plains, New York, 1986, pp
and all muscle fibers have been reinnervated. In patients with 189-200, with permission.)
Chapter 8 QUANTITATIVE EMG - 349
the MU. When the information obtained from these procedures 5~--------+-~--------------~1000 ~
•ii'
is combined, a much better picture of normal and abnormal
MUs is obtained. J83-J85
Sanders and coworkers J55 examined FD, CN MUAP, and
macro-EMG MUAPs measurements in a group of patients with
•u
..
•
4
- Strength
_"acro EMG
_ CNEMG
800 -i
m
U 3 600 !:
old polio. The neighboring fiber density (nFD) is obtained by I c;)
,..
-
= Neighboring FD
subtracting 1 from the FD value. 78 It represents the fibers other
than triggering potential that lie within the uptake area of the 400 Ei
"2
electrode. The nFD, mean CN MUAP amplitude, and mean ;:;
macro-MUAP amplitude measurements were expressed as per 200 a
centage of their corresponding normal values. The data were •
divided into three groups based on strength in the tested O~
muscle. The mean values of the normalized measurements
o 1 3 5 7 9 11 13 15 17 19 21 23 25
Duration ( Months )
from these three groups are shown in Figure 8-95. In muscles
with mild weakness, the MU size (based on macro-MUAP am figure 8-96. Quantitative EMG in a patient with ALS. The rel
plitude) is slightly increased. The MU size is maximal in the ative change in muscle strength, nFO, and eN and macro-MUAP ampli
moderately weak muscles. In severely weak muscles, the MU tude in the biceps muscle of a patient with AlS over a 2-year period as
size is slightly increased from normal, but is much less than in the muscle became weaker. Note the increase and then decrease in
the moderately weak muscles. The above pattern can also be macro-MUAP amplitude when the muscle became weaker. (From
seen in some patients with ALS as their disease progresses Nandedkar SO: Quantitative electromography in clinical electrodiag
(Fig. 8-96). The fol1owing model is proposed to explain this nosis.ln Goodgold J (ed): Rehabilitation Medicine. St.louis, Mosby.
pattern of abnormalities. 190
1988, pp 68-11, with permission.)
A normal MU consists of fibers distributed randomly
within a roughly circular territory. A small portion of the
muscle cross-section contains fibers from several different EMG parameters. Thus, the EMG examination may be de
MUs. We begin with three normal MUs, as shown in Figure ferred for a few weeks, except when the weakness is severe
8-97 A. In most neuropathies, the main disease process is a and sudden. Evidence of a few active MUs in these cases is a
loss of MUs (Fig. 8-97B). Acutely after an MU is lost (#2 in good prognostic indicator.
Fig. 8-97B), we would expect to see abnormalities in the form A few days to weeks after the insult, the muscle fibers be
of a reduced MU count, increased recruitment frequency, re longing to the lost MUs are recognized from the fibrillation po
duced recruitment ratio, and a reduced IP at maximal effort. tentials and positive sharp wave recordings on routine needle
As described earlier, these are not necessarily the most sensitive EMG.
t t
F E o
figure 8-97. Concept of MU remodeling. A, Three normal MUs have overlapping territories. B. MU # 2 is lost. C, MU # I reinnervates and
shows fiber grouping in only a small portion of the MU territory. (O) MU # I is significantly enlarged. E, MU # I is lost. Some fibers (indicated by
checkered pattern) are reinnervated. F, MU # I is fractionated. See text for details.
350 - PART II BASIC AND ADVANCED TECHNIQUES
10 10 r - - - - - - - - , Scanning
.• •.",
EJeetrode
A B
!k ..
/ \
%
~
.\
•• 1
t •
/
I
~,
!l.
./
10r------~, 10.--------,
t \i .•
I I
I'
.-//
3
i
!
c : 0
L ·J
Triggering
Electrode
Normal MU Myopathy Neuropathy
Fibe< de.say
Figure 8-99. Scanning EMG. In A, the cross-section of a normal
MU is shown schematically. The triggering electrode is placed at a
Figure 8-98. Macro MUAP and FD. The FD (A. C) and median
fixed posi' :on while the scanning electrode is pulled through the MU
macro-MUAP amplitude (B. D) in normal subjects (top) and patients
territory in 50-lim increments. The various positions of the needle tip
with myopathy (below). Note the slight increase in FD in myopathy.
are correlated to the scan in Figure 8-1 OOA. In B, a cross-section of
There is a shift towards smaller macro-MUAPs. although most sub
an MU affected by a myopathy is shown. Note the areas with fiber
jects had values within the normal range. (From Nandedkar SD:
loss and fiber grouping. The dashed line represents the corridor of
Quantitative electromyography in clinical diagnosis. In Goodgold J
the scanning electrode.This MU architecture corresponds to the scan
(ed): Rehabilitation Medicine. St. Louis, Mosby. 1988, pp 68-11. with
in Figure 8-100B. Finally. the MU architecture in a neuropathy is
permission.)
shown in C. Note the fiber grouping in the bottom portion of the
territory similar to the model in Figure 8-97C. The corresponding
scan is shown in Figure 8-1 OOc.
In a few weeks, the surviving MUs begin to reinnervate the
denervated fibers from the lost MUs (Fig. 8-97C). The newly
formed collateral sprouts are short and thus only those MUs that become 10-40 times their normal size. When this occurs a small
are within the immediate vicinity of the lost MUs participate in cross section of the muscle may contain only a single MU. Ifthe
reinnervation. Therefore, the muscle fiber distribution may be CN or MN electrode is in this area, the "giant" MUAPs may be
normal in a portion of the MU territory (top half of MU #] in seen. At maximal effort, the IP may contain discharges of just
Fig. 8-97C) while there is fiber grouping in other parts (bottom one MU, i.e., discrete pattern. The recruitment frequency and
portion of MU #1 in Fig. 8·97C). Conventional recording elec ratio are increased. The FD, or CN, MN or macro-MUAP am
trodes have a small uptake area compared to the size of the MU plitude will be significantly increased. The MU-counting tech
territory. As a result, one may record normal and abnormal niques demonstrate a reduced number of MUs. On muscle
MUAPs from the same MU just by changing the electrode posi biopsy there is marked fiber type grouping.
tion. During reinnervation, the MUAP appears unstable. The If such an enlarged MU is lost (Fig. 8-97E), it represents a
earliest abnormalities during this stage are increased FD on marked decrease in the number of muscle fibers. Some fibers at
SFEMG, and polyphasic and unstable MUAPs on CN or MN the MU periphery may be reinnervated (e.g., MU # 3 or others
EMG. As reinnervation continues, fiber type grouping is seen indicated by checkered pattern), but a vast majority of fibers at
on muscle biopsy. the center are too far away to receive collateral sprouts. This
In a slowly progressing disease, reinnervation may fully com large group of fibers atrophy and remain denervated. The
pensate for the lost MUs and the surviving MUs are enlarged muscle biopsy shows grouped atrophy of muscle fibers. On
(Fig. 8-97D). It is entirely conceivable that individual MUs may EMG the MUAPs are unstable and their waveform may exhibit
A B c
significant differences. Significant spontaneous activity (e.g., pulled through the entire MU territory. The sequential plot of
fibrillations, positive sharp waves, etc.) is also observed. Loss MUAPs is called the "scan" (Fig. 8-100).
of large MUs implies reduced macro and concentric MUAP am When the needle tip is positioned deep within the muscle and
plitude. Since this loss remains uncompensated, the patient may outside the MU territory (position 1, Fig. 8-99), the potential
present with new onset or rapid progression of weakness in the registered by the cannula of the concentric needle is recorded
muscle. (Fig. 8-100A, traces at the top). This is similar to the Macro
It is also postulated that the motor neuron may not be able to EMG recordings, except the waveform appears inverted since
support nutritionally the enlarged pool of muscle fibers. Thus, the cannula is the reference electrode. As the electrode is pulled
some muscle fibers are lost, which reduces the MU size. This in steps of 50 11m, it enters the MU territory (position 2, Fig. 8
phenomenon is called fractionation (Fig. 8-97F). The newly 99). The electrode records a sharp MUAP with low rise time
denervated fibers may not become reinnervated if the remaining (Fig. 8-100A, traces in the middle of scan). Its spike component
MUs have also reached their capacity for reinnervation. This is defined by muscle fiber organization within that portion of
can also result in new onset or rapid progression of weakness. the MU territory. Therefore, the shape of the MUAP continues
Muscle biopsy will show atrophic muscle fibers, perhaps in to change as the needle is withdrawn. The last occurrence of
small to moderate groups. Some MUAPs may appear to have spike activity is seen as the electrode exits the MU territory
low amplitude and polyphasic waveform, a characteristic often (Fig. 8-100A, position 3 in Fig. 8-99). When the needle is su
associated with myopathy. Thus, severely weak muscles should perficial and outside the MU territory (position 4 in Fig. 8-99)
be avoided for EMG testing and muscle biopsy. Similar models no MUAP activity is registered (bottom-most traces in Fig. 8
have been postulated for MU remodeling by Emeryk-Szajewska l00A). This defines the diameter of the MU territory.
and Kopec. 60 The middle scan in Figure 8-100 was performed in a patient
In many myopathies muscle fibers are lost (Figs. 8-1 and 8-99). with myopathy. The size of the MU territory is not reduced.
This is compensated by regeneration and hypertrophy of fibers. However, we find sections within the scan with no MUAP activ
As a result, the number of fibers may be reduced only slightly. ity. This represents the area of the MU where muscle fibers have
The MU territory contains some areas that do not have muscle been lost, called silent areas. They cannot be recognized on the
fibers. However, we cannot recognize them on the EMG exami routine needle EMG examination. Once again a variety of
nation. Other parts of the MU territory have focal grouping of MUAP waveforms can be seen recorded from the same MU.
muscle fibers due to regeneration and or reinnervation. This com Initially, the MUAP is simple with a short duration reflecting
bination of disease processes gives increased FD on SFEMG, but loss of fibers from the MU. This is followed by a silent area also
normal or reduced macro-MUAP amplitude (Fig. 8-98).91 indicating fiber loss. Later, we can see complex waveforms of
long duration due to variability of fiber diameter. In patients
SCANNING EMG with myopathy, the number of silent areas is increased.84.91.188
The scan in Figure 8-10OC was performed in a patient with
The above concepts of MU reorganization are vividly de neuropathy. Notice that there is no significant change in the MU
scribed by a technique called scanning EMG.179 In this technique territory. Initially, the MUAP waveform is normal. Later
(Fig. 8-99), an intramuscular needle electrode is positioned to polyphasic and unstable MUAPs are found. A late component is
trigger the sweep by a MUAP from a single MU. A second elec also seen, representing the portion of MU where reinnervation
trode is inserted through the same MU territory to record activity is taking place.
from the same MU. When the MU discharges, the delayed The scanning EMO demonstrates the variability of MUAP
MUAP is recorded and displayed with a delay. The second elec waveforms within the MU. It shows that the disease processes
trode is pulled out by 50 JlItl, and another MUAP is acquired and do not affect the MU in a homogeneous fashion. It further em
displayed. The process is repeated until the electrode has been phasizes the need to search different corridors within the muscle
myasthemia gravis; MS. myasthenic syndrome;ALS. amyotrophic lateral sclerosis; GBS. Guillain-Barre syndrome;·. suitable for monitoring.
From Stalberg EV: Electrodiagnostic assessment and monitoring of motor unit changes in disease. Muscle Nerve 1991; 14:292-303. with permission.
to assess MUAPs. Different sites should be separated by a few onset, progression and prognosis of the disease making EMG an
(5-10) millimeters to avoid duplicate recordings from the same even more powerful test procedure.
MU. While quantitative analysis is a powerful tool, it is also time
consuming. Considering patient discomfort, time, diagnostic
OTHER QUANTITATIVE METHODS sensitivity and specificity, and cost and reimbursement, we
must make a judicious choice of the test procedures to be used
In this chapter we have reviewed the routinely used quantita for clinical electrodiagnosis.187.219 A technique suitable for di
tive test procedures to assess changes in the MU architecture agnosis (Table 8-17) is not necessarily suitable for follow-up
and number. The MU is also affected by other disease and monitoring the disease progression (Table 8-18). This se
processes. As an example, disuse of a limb after immobilization lection may vary among different investigators, their expertise,
results in atrophy but there is no change in muscle fiber distrib and resources. Nevertheless, the exercise allows one to gain a
ution or the number of MUs. The change in fiber size reduces better understanding of the diagnostic sensitivity and speci
its action potential propagation velocity.66.173 When the mechan ficity of the various QA procedures, and their relationship to
ical apparatus of the muscle is affected, the EMG may be the MU.
normaL Nevertheless, we could study the contractile properties
of the motor units using EMG recording procedures.33.45.50.149.217
Surface EMG offers the benefit of noninvasive and painless test ACKNOWLEDGMENTS
procedure. It would be of great interest to develop new tech
niques for diagnosis, prognosis, and monitoring different neuro The first author would like to thank Oxford Instruments for
muscular diseases.116.123.J5J With high-quality amplifiers and support in this project. The assistance by Mr. Desh Nandedkar
signal-processing techniques, we can now follow individual in drawing and editing the figures is greatly appreciated. Most
MUs as they are affected by disease processes. 48 •S3 As stated ear are reproduced with permission from the Center for Academic
lier, we may not be able to use these techniques in a routine Scholastic Achievement (www.casaengineering.com).
clinical environment. Yet it is the quantitative analysis that will
increase our understanding of the pathophysiology and progres
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lS6 - PART II BASIC AND ADVANCED TECHNIQUES
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Chapter 9
Somatosensory Evoked
Potentials
Daniel Dumitru, M.D., Ph.D.
Lawrence R. Robinson, M.D.
Machiel J. Zwarts, M.D., Ph.D.
Somatosensory evoked potentials (SEPs) are waveforms that the supervising physician must directly acquire the technical ex
can be recorded from the peripheral nerve, spinal cord, and/or pertise necessary to perform all types of SEPs (upperllower
cerebral cortex following excitation of a peripheral nerve or cu limb, dermatomal, segmental, etc.) and gain complete familiar
taneous afferents. The beginning practitioner of electrodiagnos ity with waveform interpretation and the various technical arti
tic medicine may be a bit wary of performing SEPs because of facts that may contribute to an erroneous diagnosis. Waveform
inexperience recording these responses. This may simply be a distortions may result from inappropriate filter parameters,
lack of training or, in some institutions, the SEP may be desig stimulus intensity/frequency effects, suboptimal signal-ta-noise
nated as a study obtained by electroencephalographic or elec ratio, and increased skin-electrode impedance, among other fac
trodiagnostic technicians for later waveform review by the tors influencing data acquisition. Incomplete understanding of
physician. Prior to allowing a technician to record the infonnation, these important concepts may result in a misdiagnosis, particularly
357
358 - PART II BASIC AND ADVANCED TECHNIQUES
if the SEP waveforms are examined in isolation from the patient This was the first clear demonstration of a cortical electrical
without the opportunity to collect additional information. Thus, event obtained through electronic averaging, 74,75
as for the needle EMG examination, SEPs should be viewed as The ability to electrically activate a peripheral nerve and av
a dynamic test, with the plan for a specific patient varying as erage the ensuing depolarization at some other location in the
new information is obtained. neuraxis was not available prior to 1947. Before Dawson's in
The vast SEP literature can be formidable for the novice prac strument, all evoked potentials were recorded on a freely r:un
titioner because of a lack of standardization regarding recording ning trace. The potentials were difficult to observe because of
techniques and waveform nomenclature. To some extent, the the background noise, which tended to obscure the waveforms
SEP examination can be conceptualized as simply a nerve con of interest. Unlike the comparatively larger electroencephalo
duction study over a relatively long portion of both the periph graphic potentials, which are essentially unrelated to specific
eral and central nervous systems. As most practitioners are sensory input, the few-microvolt SEP has a fixed temporal rela
rather familiar with obtaining nerve conduction velocities, the tionship to specific sensory stimuli. This temporal relationship
SEP is conceptually no more difficult. There is no reason why to external excitation results in the "evoked" aspect of the SEP.
an individual who routinely obtains nerve conduction velocity The relatively large EEG potentials combined with the environ
data cannot, with proper instruction and practice, successfully ment's electrical interference require the rather small SEPs to
acquire SEPs. be extracted from this significant background activity.
This chapter approaches the SEP examination from a practi Dawson's74.75 instrument was capable of minimizing the random
cal standpoint with the goal of demystifying SEPs and perform background electrical noise and observing time-locked SEPs
ing routine upper and lower limb studies in an efficient manner. relatively free of noise contamination. Dawson's74.75 electronic
Although there are some aspects of SEPs that are poorly under averager summated the regular occurrences, i.e., evoked wave
stood, it is not necessary for the beginner to become embroiled forms, while the random noise was reduced over time. This
in these complexities. Rather, it is far more productive to master technique improved the signal-to-noise ratio. Development of
the fundamentals of SEP techniques and data acquisition. the average response computer (ARC)54 by 1958, and further re
Because SEPs are relatively new to many individuals, a good finements in instrumentation, has permitted the pioneering work
beginning point is to briefly consider the historical aspects that of Dawson to be applied routinely in SEP investigations today.
led to the development of the modem SEP evaluation.
A. fiber ~I------------------------------II~-"------:·---.~--l
Myelinated fiben UUlDl-
diameter: i.o IS 10 5 I 1.0 0.5,.
~;------~i~----~ir-------~:------~il' \
120 90 60 JO , 1.0 0.5m1_
I i i i" I
: I I I I I
C. fiber clul:
(G...., 1-1--A~ I I II
t--A,.----4 C ,
I I I---U ____ t-Al-fl I
I I I I J •
D. function:
skin .fferents
E. Motor fiben:
From Shepherd GM: Neurobiology. New York, Oxford University Press, 1983, p 258, with permission.
sensory portion of the cerebral cortex.145.146 It is important to travel in the anterolateral aspect of the spinal cord. 22,134,330 As
distinguish which sensory fibers are activated by the designated noted above, the lemniscal tracts convey data from those so
impulse parameters and the portions of the spinal cord convey matic receptors concerned with muscle stretch, joint position,
ing these action potentials to the cerebral cortex. In this discus vibration, and tactile/pressure stimuli.56 The cell bodies of these
sion, we will use the Lloyd classiftcation207 system when first order afferent nerve fibers are contained in the dorsal root
referring to different types of sensory nerve fibers. ganglia. Following propagation through the dorsal root entry
In the cat, delivery of 1.5 to 2 times the IA fiber threshold ex zone, impulses along the lemniscal system enter the ipsilateral
clusively activates the IA fibers. 16 At stimulus intensities above 2 dorsal columns and travel rostrally (Fig. 9_1).38.135 The action
times the IA threshold, group II fibers are excited. Minimal toe potentials within these first-order nerve fibers terminate by
or thumb twitch in humans preferentially activates group I synapsing in the dorsal column nuclei, i.e., the nucleus gracilis
(12-20 1lIIl) and possibly group II (4-121lIIl) nerve fibers. 34,3s.163 and nucleus cuneatus in the lower region of the medulla (Fig.
The small group III and IV fibers (1 to 4 1lIIl; nociceptive affer 9_1).38.135.253.306.315.318
ents) require rather high (possibly painful) current intensities and Lemniscal fibers from the lower limbs are anatomically lo
are most likely not activated. Table 9-1 demonstrates that group I cated in the most medial aspects of the dorsal columns (Fig. 9
and II nerves convey vibration, proprioception, high threshold 1). These first-order fibers synapse with second-order neurons
pressure, and afferent input from the primary and secondary in the nucleus gracilis.m.m.3Is Nerve fibers conveying dorsal
muscle spindles as well as the Golgi tendon organs and pacini an column data from the upper limbs are located more laterally, but
corpuscles. Once the nerve fibers conveying this information are adjacent to the lower limb nerve fibers. Upper limb afferents to
activated, action potentials travel centripetally to enter the spinal the lemniscal system synapse in the nucleus cunea:tus, which is
cord through the medial aspect of the dorsal root entry zone. The positioned lateral to the nucleus gracilis, from which originate
above noted sensory inputs compose the lemniscal system.22.134 second-order neurons representing the upper limb.22.134.30s.315
The second-order nerve fibers from the dorsal column nuclei
CENTRAL NERVOUS SYSTEM PATHWAY immediately cross to the contralateral side of the brain stem,
forming the decussation of the medial lemniscus, and continue
The lemniscal (dorsal column) system is a term utilized to their rostral ascent as the medial lemniscus itself (Fig. 9
distinguish a portion of the afferent somatic fibers that do not 1).22.134.318 This tract terminates by synapsing in a specific region
360 - PART II BASIC AND ADVANCED TECHNIQUES
V-' posterior
nucleus of lhalamus
Nucleus
cuneatuS
Fasciculus _----_:::t::::::\"Y"y-y............
cuneatus
Cervical level
Oo<>al
.pinocetebellar
tract
------"1
Nucleus dorsalis-_~~M'
Thoracic level
ICIa"'e', column)
fasciculus
gracilis ------_~!iIJ
lumbosacral level
of the thalamus, the ventral posterolateral nucleus or VPL the lateral funiculus may convey a significant portion of the type
(Fig. 9-1). Third-order nerve fibers originating in the VPL, thal IA and II afferent information to the somatosensory
amocortical fibers, project to the postcentral gyrus of the pari cortex. 55•197,229.254 The proposed pathway is a continuation of pri
etal lobe, known as the somatosensory cortex (Fig. 9_1).123 A mary afferents that synapse at the level of Clark's column to
characteristic topographic arrangement of sensory regions is then ascend in the dorsal spinocerebellar tract and subsequently
discretely arranged along the cortex corresponding to lemniscal in the nucleus Z at the level of the medullopontine junction (see
fibers from specific portions of the body, forming the so-called Fig. 9-1).214 Nerve fibers from nucleus Z then travel to the
homunculus (Fig. 9-2).134 The somatosensory region represent medial lemniscus and ascend to the rostral region of the VPL.
ing the upper limb is located on the cortex superior to the face The traditional pathway from the VPL to the somatosensory
area. The lower limb somatosensory representation, however, is cortex then serves as the final pathway for the fibers from the
along the medial aspect of the cerebral hemisphere, separated lower limb.
from its contralateral body region in the opposite hemisphere by
the interhemispheric fissure. SEP SPINAL PATHWAY
With respect to the lower limb somatosensory information, a
second fiber route has been proposed, i.e., the spinomedul In performing SEPs, the peripheral nerve is stimulated and
lothalamic tract. 318 This view suggests that the dorsal aspect of there is no debate as to the initial presumed pathway, i.e., the
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 361
dorsal cordotomy, intradural needle recordings support the fossa 2-3 cm superior to the insertion of the posterior border of
assertion that the dorsal columns are a primary pathway con the clavicular head of the sternocleidomastoid muscle. An addi
veying SEP impulses. 121.122 tional set of electrodes is placed over the cervical spine with the
active or E-t electrode positioned over the second, fifth, or sev
enth cervical spinous process and referenced to an electrode (E-2)
NEURAL GENERATORS OF SEP located about the forehead region. 6,7 The seventh spinous pr~ess
WAVEFORMS is preferred by some investigators because of easily identifiable
bony landmarks. 326 Finally, an E-t electrode is secured to the
A neural generator may be defined as nervous tissue such as scalp overlying the contralateral somatosensory cortex referenced
axon, cell body, or synapse with the capability of generating or to the previously noted forehead region. The preceding recording
sustaining an action potential. A series of recording electrodes electrodes are most often utilized for the routine SEP examina
located on the peripheral or central nervous systems' pathway tion of most nerves excited in the upper limb.
along which the action potential propagates will document a
series of waveforms associated with the action potential as it Lower Limb
passes beneath the electrodes. The waveforms detected are re When stimulating the tibial nerve at the medial malleolus, an
ferred to as traveling waves because they represent the propa E-l recording electrode is placed over the tibial nerve at the
gating action potential. A collection of cell bodies and neural popliteal fossa and referenced to an E-2 electrode positioned at
synapses forming a nucleus can also generate a relatively well the medial aspect of the knee. 6,7 A second E-l recording elec
localized region of depolarization. The waveform produced by trode is usually located over the spinous process of the third or
this stationary collection of action potentials is a stationary fourth lumbar vertebra with an E-2 electrode on a spinous
wave. As you might expect, the waveform detected from this process 4 cm rostral, or located on the iliac crest contralateral to
type of neural generator does not propagate, but has a restricted the side of stimulation. A third E-I recording electrode is at L I
spatial distribution. Recording electrodes positioned along pe or TI2 and referenced to an E-2 electrode positioned 4 cm ros
ripheral and central neural pathways can detect both stationary trally on a spinous process or to the iliac crest contralateral to the
and traveling waves, depending upon the electrodes' location stimulated limb. The final E-l electrode is secured to the scalp
(see below). just posterior to the vertex of the skull such that it is superior to
the somatosensory cortex for both lower \limbs and is referenced
RECORDING ELECTRODE LOCATIONS to the forehead region. 6,7 Occasionally, cortical recording elec
trodes located just lateral to the vertex location may aid in the
The American Electroencephalographic Society (AES) rec detection of waveforms not optimally observed at the vertex sec
ommends a number of standard locations for electrode place ondary to individual patient anatomic variations.
ment when recording SEPS.6,7 In this section, we wiII refer to the
relevant active (E-I) and reference (E-2) recording electrodes' WAVEFORM GENERATORS: UPPER LIMB
generic anatomic positions for obtaining a waveform so that we
can discuss SEP generators. A discussion of the preferred elec Erb's Point
trode and waveform nomenclature is provided in the subsequent Within approximately 9 or to ms following median nerve ex
section. This chapter will only consider short-latency SEP re citation, a relatively large waveform with a distinct negative peak
sponses. For upper limb studies, a short-latency response is de is detected by the electrode at Erb's point (Fig. 9-3).116This po
fined as a waveform occurring within approximately 25 ms of tential is believed to represent the afferent neural volley passing
the stimulus in normal persons. 6.7 Normal lower limb short-la under the electrode at Erb's point. 48-51 ,105 This waveform is first
tency SEPs are usually generated within about 50 ms of the ex generated at the lateral margin of the clavicle as substantiated by
citing pulse. SEPs resulting from stimulation of the median direct peripheral nerve recordings. Further proof of the potential
nerve at the wrist and tibial nerve at the medial malleolus are arising from the brachial plexus is that it is absent in patients
used as SEP examples to illustrate the major SEP waveforms and with lesions of the brachial plexus but present in patients with
their associated presumed neural generators. 1l7•326 Mid-latency cervical root avulsions. 14,15,65,114,142,174,176,196,322 A root avulsion
and long-latency responses can also be recorded after peripheral spares the dorsal root ganglia, thus preserving the sensory pe
nerve stimulaton; however, these longer latency responses are ripheral nerves conveying afferent median nerve impulses.
more variable and less clinically useful compared with the short The specific fibers activated in the median nerve at the wrist
latency responses discussed below. Additional nerves and wave that yield the Erb's point waveform are muscle afferents present
forms are discussed later. It is important to remember that the at that level,54,246,284 Certainly, sensory fibers subserving cuta
latencies described below for particular waveforms may vary by neous sensation also add to the entire peripheral nerve response.
several milliseconds depending upon the exact site of stimula The root levels represented in all of these fibers no doubt cover
tion, patient's height, limb temperature, and type of recording levels through most of the brachial plexus such as C-6 and C- 7
parameters utilized. for cutaneous sensation, and C-8 and T-t for the muscular affer
ents. It is also likely that the peripheral location of the Erb's
Upper Limb point electrode permits not only the recording of orthodromic
With respect to upper limb SEPs, one of the most reliable and sensory impulses but also to some extent the antidromic motor
easiest nerves to investigate is the median nerve at the wrist. impulses induced by the electrical stimulation of the median
Usually, separate examination of left and right upper limbs is nerve. Recall that peripheral nerve excitation produces action
required for a complete investigation. The first set of electrodes potentials in both motor and sensory fibers both orthodromi
is typically placed at the left and right Erb's point. 6,7 The Erb's cally and antidromically. Essentially, the recording at Erb's
point electrode contralateral to the side of stimulation is used as point represents a mixed nerve action potential containing both
the E-2 electrode. Erb's point is that region of the supraclavicular sensory and motor impulses.
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 363
STIM "10
~~-.----~----------
+-
STIM
o 10 20
I
30
I
40
I
50 msec
I
I I
Figure 9-3. Median n.!!rve SEP. Median nerve upper limb SEP utilizing a 4-channel recording technique. The bottom trace signifies an Erb's
point recording (EP =N9; EP2-EP I) demonstrating the peripheral nerve volley. The spinal recording (C5S-FZ) demonstrating the waveform
recorded at this location. The third trace from the bottom is a far-field recording (noncephalic reference {C3'-EPI}). Top trace shows the typical
negative/positive cortical potential with a cephalic E-2 electrode (C3'-FZ). (From Spehlmann R: Evoked Potential Primer. Boston, Butterworth
Publishers. 1985. with permission.)
Cervical Spinous Process electrode array over the sternocleidomastoid muscle ipsilateral to
A prominent negative potential is usually detected by an elec the side of stimulation reveals a traveling wave just after the Erb's
trode located at the C2, C5, or C7 spinous process following point potential. This traveling PPV wave is believed to represent
median nerve excitation (Fig. 9-3). Depending upon the instru the afferent impulses propagating through the proximal portion of
ment's sensitivity and degree of background noise, the main the brachial plexus and the cervical nerve roots (Fig. 9-4, Table 9-2).
peak of this potential may occasionally be preceded and fol A traveling negative waveform (DCV), first peak of the occa
lowed by small negative peaks arising from the main negative sionally tri-peaked negative cervical spine potential, can be se
potential with latencies of approximately 12 ms and 14 ms, re quentially recorded over the cervical spinous processes at about
spectively. Considerable research has attempted to define the 11 or 12 ms (Fig. 9-3).116,131 This potential is most likely the Nil
generators of these negative peaks.
In attempting to define the neural generator(s) responsible for
the waveforms recorded from the cervical spinous processes
noted above, investigators have focused on five areas of study.
These five areas include the (1) waveform's spatial distribution,
(2) generator dipole spatial orientation, (3) associated action po
tential's refractory period, (4) effect of focal lesions, and (5)
correlation with animal data. 27o A waveform's spatial distribu
tion allows one to determine if the associated neural generator is
propagating or stationary. The orientation of the generator's
dipole, as determined by its recorded waveform's peak polarity
orientation, suggests if it is pointing in a particular direction
e.g., superior/inferior or anterior/posterior. Propagating action
potentials have refractory periods considerably shorter (3-4 ms)
than stationary generators (6-10 ms). Patients sustaining well
localized lesions of various portions of the neuraxis provide in
vestigators with valuable information regarding potential
candidates for anatomic neural generator sites. Fina1\y, experi
mental lesions placed at different locations in animals can also
contribute to possible generator site identification.
When electrodes are placed over the cervical spine and refer Figure 9-4. Traveling wave. Cervical spine to anterior neck mon
enced to the anterior portion of the neck, three negative wave tage revealing the proximal plexus volley (PPV), dorsal column volley
forms occurring after the Erb's point potential can be recorded (DCy), and the cervical potential (eERV N13). The Erb's point poten
following median nerve stimulation (Fig. 9-4). These three tial is also shown. (From Emerson RG. Seyal M, Pedley TA:
waveforms are the proximal plexus vo1\ey (PPV), dorsal column Somatosensory evoked potentials following median nerve stimulation.
volley (DCV), and the cervical potentia1.67.79.80-83,1I6 A linear I.The cervical components. Brain 1984; 107: 169-182, with permission.)
364 - PART II BASIC AND ADVANCED TECHNIQUES
Modified from Seyal M Gabor AJ: Generators of human spinal somatosensory evoked potentials. J Clin Neurophysiol 1987;4: 177-187.
peak noted in Figure 9-3 preceding the major N13 peak. There Lesion studies demonstrate that the 13a potential is absent fol
is approximately a I-ms difference between the caudal and ros lowing obliteration of the dorsal hom cells, while the 13b potential
tral aspects of the cervical spine with respect to the traveling remains unchanged. 178 Additionally, lesions in the cuneate nucleus
wave's peak latency for this potential. The refractory period of resulted in an absence of the 13b waveform but preservation of the
this waveform is short, several milliseconds, suggesting that its 13a potential. The generators of the 13a and 13b potentials, there
origin is from a conducting neural volley, presynaptic impulse, fore, are believed to be the dorsal gray of the cervical cord and the
and does not involve post-synaptic nuclear generators (Table 9 cuneate nucleus, respectively. Combined studies involving stimula
2). This traveling waveform most likely represents the afferent tion of lower limb nerves and their effect on the two 13-ms peaks
volley propagating rostrally in the dorsal columns of the cervi further substantiated the two waveforms generators noted
cal spinal cord. 62 .82 ,83,116,158,211 The dorsal root entry zoneI74.211.321 above. 26 8-271 Additionally, hypothermia reduces the amplitude of
and dorsal hom 216,266 have also been postulated as sites of origin this waveform, suggesting that synaptic transmission is involved in
for the waveform, This potential is designated NIl/NI2 by its production because a traveling wave would have increased in
some investigators. Hypothermia studies demonstrate an in magnitude similar to that found in the dorsal column studies. 298 The
crCdse of the waveform's amplitude similar to that found in dorsal columns at the superior cervical,204.303 mid-cervical,324.326.327
peripheral nerves, supporting the dorsal column volley proposi and foramen magnum 140,211 levels were also proposed as possible
tion, i.e., propagating neural volley.27,298 If the generator of this generator sites for the NI3 potential (Table 9-2). The negative peak
waveform were a post-synaptic potential in a collection of with a 14-ms latency constituting a portion of the cervical spine po
nuclei, e,g., brain stem nuclei, the amplitude should have de tential is believed to arise from the afferent neural volley propagat
creased, as this is the anticipated response of these cells to a re ing in the medial lemniscus.82.83 ,152.153.168,292 The N13 and Nl4 peaks
duction in temperature. likely represent generators below and above the foramen magnum,
The second negative peak of the major negative spinal poten respectively.327 The various subcomponents of the spinal potential
tial occurs at about 13 ms and is essentially a stationary potential can often be best observed using a noncephalic referential mon
demonstrating its greatest amplitude over the cervical root entry tage, e.g., an E-2 electrode located on the ear lobes.
zone (Fig. 9-3).82 An experimental electrode montage over the
anterior cervical region records a positive waveform with the Scalp
same latency as the negative cervical potential. 116,117 Esophageal A large negative potential usually presenting a peak latency at 19
electrodes have also documented this positive waveform. 83,86 or 20 ms after median nerve wrist stimulation is typically recorded
These findings suggest that a dipole is present in the cervical with a scalp electrode over the contralateral somatosensory cortex
region oriented such that the negative pole is directed posteriorly (see Fig. 9_3).139 The negative peak is then followed by a positive de
while the positive pole faces anteriorb:, substantiating a station flection with a peak latency approximating 22 ms. One proposal sug
ary neural generator producing the NI3 potential. gests that the negative potential originates in the primary relay nuclei
Investigations examining the refractory period of this poten of the thalamus, whereas the positive potential reflects somatosen
tial have demonstrated a relatively long refractory period, sug sory cortical activity induced by the arrival of the afferent im
gesting the involvement of synaptic transmission (Table 9-2).166 pulseS.49,51,52,140.219,227,234.235 This view is now considered less accurate
These findings have led some investigators to suggest that the than the suggestion that the large negative and subsequent positive
site of generation of this waveform is within the intemeurons of peaks both reflect cortical arrival of the impulses generated at the pe
the cervical cord's dorsal gray matter. 82 ,83 Further refinements in riphery.3.79.80,83,159,220,221.280,321 Lesions involving the postcentral sulcus
recording techniques substantiated that the 13-ms negative peak support the view of the somatosensory cortex producing the large
may also display a bifid character, 13a113b, implying two dis negative and positive potentials at 20 ms and 22 ms, respectively.
tinct generators. 2,82,174,196.281,298 These two generators appear to Occasionally, a distinct negative peak at 18 ms, 17 ms in some
have a spatial separation resulting in a temporal difference of I studies, superimposed on the larger 20-ms negative waveform
ms between the 13a and 13b peak latencies. may be observed. This 18-ms negative potential has a rather
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 365
----~"---
the thoracic spine potential demarcating central nervous
system entry of the potential volley.The top trace shows cor
tical arrival at the somatosensory cortex (CZ'-FpZ'). (From
Spehlmann R: Evoked Potential Primer. Boston, Butterworth
Publishers, 1985, with permission.)
oI 10
I
40
I
+-
STIM
wide distribution over the scalp, suggesting it arises from a (Fig. 9_6).268-271 The conduction velocity of this negative waveform
rather deep structure capable of projecting its waveform some is essentially constant along its course. This potential merges with,
what uniformly over the cranium's surface. This potential was and then departs from, the stationary waveform recorded at the
initially suggested to arise from neural activity in the thalamus twelfth thoracic spine (see below), indicating a traveling wave as
and/or thalamocortical radiations. 83 The thalamus appears to be cending the spinal cord with a conduction velocity approximating
a reasonable structure to generate this waveform given that the 61 rnlS.268 A refractory period of 1-2 ms is noted for this traveling
IS-ms negative potential precedes that of the cortical waveform. volley when determined over the sacral or thoracic region (Table 9
Various lesions in patients with thalamic pathology support the 2). A short refractory period suggests that synaptic relays are not
view that the IS-ms negative peak is associated with the thala associated with the propagation of this wavefront from the lower
mus or its projections to the cerebral corteX. 22 1.303.32S limb to the thoracic aspects of the spinal cord. The negative wave
form, therefore, recorded over the third lumbar vertebra most likely
WAVEFORM GENERATORS: LOWER LIMB represents the traveling peripheral nerve volley (cauda equina) as it
progresses through the lumbosacral plexus and nerve roots (Table
Popliteal Fossa 9_2).64.76.175 This same propagating potential, when detected over
Similar to the Erb's point recording in the upper limb, the the thoracic spines, is believed to be the traveling wavefront ofelec
popliteal fossa electrode is positioned directly over a peripheral trical activity ascending the dorsal columns.
nerve pathway. A clearly delineated negative potential that may
be preceded and followed by smaller positive deflections is usu Twelfth Thoracic Vertebra
ally obtained with this electrode montage (Fig. 9-5). The nega The T-12 recording electrode documents a well-defined nega
tive peak latency typically occurs at approximately 7-10 ms, tive potential with a peak latency of approximately 21-22 ms
depending upon the distance between the site of stimulation and (Figs. 9-5 and 9-6). As always, the exact latency of this poten
recording and nerve conduction velocity.6.7.179,282 This potential tial is dependent upon the length of the individual's leg and po
arises from the afferent neural volley traveling in the tibial nerve sition of the stimulating electrodes. Unlike the potential
as it passes beneath the recording electrodes. recorded with the L-3 electrode, the T-12 waveform has a rela
tively restricted spatial distribution. 268 The magnitude of this po
Third Lumbar Vertebra tential maximizes within 5-15 cm rostral to the L-4 spinous
An electrode located over the third or fourth (some investiga process.zs8 Locations either more superior or inferior result in a
tors prefer L4 because it is easy to locate) lumbar vertebra, with diminution of this potential's amplitude.
an E-2 electrode several levels more rostral, records a small Recordings over the anterior abdominal wall and thorax
negative potential that may occasionally be associated with a demonstrate a positive potential with the same latency and tem
preceding and/or trailing positive deflection (Fig. 9-5).62 The poral aspects as that of the negative waveform recorded from
negative peak latency normally ranges between 17 and 21 ms, the thoracolumbar spines. 267 Additionally, identical amplitude
corresponding to the length of the subjects' lower limb and site characteristics to those observed for the 22-ms negative poten
of stimulation. 282 Insight is gained into spinal generators by con tial are found for this positive potential. Similarly, findings of a
sidering the five investigative methodologies utilized for cervi positive potential with the above aspects are demonstrated with
cal spine generators previously described. an esophageal electrode.84 The dipole orientation of this potential
Sequentially placed electrodes along the spinous processes of appears to be oriented in the transverse direction (Table 9-2).
the entire spinal column demonstrates a negative waveform with a These findings support a well-localized potential originating
linear increase in peak latency from the sacral to the cervical region from the spinal cord about the T-12 region.
366 - PART II BASIC AND ADVANCED TECHNIQUES
Z
Although not routinely performed, a recording electrode
over the second cervical spine records a stationary potential
W
()
25 following bilateral tibial nerve stimulation. 268 ,21o This potential
Z demonstrates a latency of about 29 ms following activation of
~
(J) 30 the tibial nerve at the medial malleolus. The potential is first
is noted at the lower cervical region and cannot be detected
35
above the inion (Fig. 9-7), It is also possible to distinguish the
29-ms negative potential from the ascending dorsal column
volley. Animal studies reveal that the orientation of the nega
"0 tive potential is axiaL 177 A rather long refractory period is
noted for this cervical potentia1. 268,27o All of this strongly sug
.5 gests that the origin of the 29-ms negative potential is most
ROSTAAL ~I"V likely in the nucleus gracilis.
IS
lICIt . .
fication and amplitude measurement. In attempting to compare
IselIn
data from one laboratory to another, obvious difficulties arise with
respect to the occurrence of particular waveforms as they relate to ., "
II
II kllllIeII!_U~ IINIOIIIII
specific neural generators. This chapter will attempt to follow the
IS
AES guidelines as closely as possible unless otherwise stated. It is UNION•• '
cz.~
..J
hoped that the reader finds that the authors' justification for devia cz·
tions from the presented recommendations result in clarity and do
not add to the already confusing literature regarding SEPs.
Figure 9-7. Tibial nerve traveling waves. Recording along the
spinal column from sacral region to skull demonstrating various wave
NOMENCLATURE FOR RECORDING forms along the neuraxis following bilateral tibial nerve stimulation. Note
ELECTRODE SITES that the traveling neural volley ascends along the spinal axis and inter
sects the two stationary potentials at the thoracolumbar junction and
The placement of E-I and E-2 electrodes influences the de cervical region. (From SeyaJ M, Kraft LVII, Gabor AJ:A cervical synapse de
tection of different waveforms. In general, when the E-I and E pendent somatosensory evoked potential following posterior tibial nerve
2 electrodes are relatively close to each other, a bipolar stimulation. Neurology 1987;37: 1417-1421, with permission.)
montage is created. When these 2 electrodes are located close
to a neural generator, a relatively small potential devoid of elec
trical events occurring at some distance from the recording site the main cortical waveform. The site of origin for these far-field
is detected. The reason for the absence of events at a distance, potentials remains controversial and is discussed at the end of
i.e., from the far-field, is because this electrical activity is elimi this chapter, as these potentials are of little clinical utility at the
nated as a common mode signal by the differential amplifier present time with respect to identifying pathology involving the
(see Chapter 3). The net result is the detection of the difference peripheral or somatosensory neural pathways.
between the two rather closely spaced electrodes with elimina
tion of potentials observed simultaneously by both recording ELECTRODE SITE DESIGNATIONS
electrodes at a distance. Of course, if one could place both the
E-I and E-2 electrodes in the same location, no waveforms Upper Limb Stimulation
would be detected, as all signals would then be common to both Erb's Point. When performing upper limb SEP studies irre
and subsequently rejected by differential amplification. spective of whether the median or ulnar nerves at the wrist or
An E-2 electrode placed on the scalp and connected to an E-I cutaneous digital branches of these nerves are excited (or any
electrode on the scalp or cervical spine is referred to as a other upper limb pure sensory or mixed nerve, for that
cephalic reference montage. 6.7 In this type of arrangement, cor matter),281 a standard number of recording electrodes are uti
tical neural generators producing the anticipated waveforms lie lized. As previously noted, the first set of electrodes are located
relatively close to the E-I recording electrode. It is important to over the left and right Erb's point (Table 9-3).6.7 An Erb's point
keep in mind, however, that the E-2 electrode is most likely recording serves several functions: (l) documents that a periph
recording a volume-conducted response from the activated corti eral nerve volley has reached this proximal anatomic location,
cal neural generator and, therefore, is not actually electrically (2) allows one to evaluate the response with respect to slowing
silent. The end result is an SEP waveform with some activity because of limb length or decreased temperature, and (3) per
arising from the E-2 electrode. This is the type of SEP we will mits the evaluation of peripheral nerve slowing as a cause for a
discuss in the majority of this chapter. As one might anticipate, it central delay. The two electrodes positioned 2-3 cm superior to
is also possible to position an E-I recording electrode on the the clavicle and just lateral to the clavicular head of the stern
scalp over a portion of the somatosensory cortex of interest (e.g., ocleidomastoid muscle are designated EPI and EP2 for the left
upper or lower limb location) and reference this electrode to the and right sides, respectively.6.7 In general, electrodes placed on
contralateral limb with respect to stimulation. For example, one the body are given odd numbers when located left of midline
can place an E-I electrode on the right parietal somatosensory and even numbers when right of midline. 46,47.169.231 These two
cortex representing the upper limb when activating the left electrodes are typically combined for a left-right or right-left
median nerve at the wrist, and use the right wrist as the location Erb's point montage. The Erb's point electrode defined as E-I is
for the E-2 electrode. This set-up is referred to as a noncephalic ipsilateral to the stimulated limb. Should left upper limb nerves
reference or referential montage, which often produces more be stimulated, EPI is the E-I electrode and EP2 is the E-2 elec
"noise" than the bipolar montage. 6.7 In this instance, a number of trode. In this case, EPI is referenced to EP2. With right upper
positive potentials called far-field potentials are recorded preceding limb activation, EP2 is the E-I electrode, while EPI is the E-2
368 - PART II BASIC AND ADVANCED TECHNIQUES
Table 9-3. SEP Recording Electrode Placement cervical vertebra and then counting the appropriate number of
Channel # E- I Electrode E-2 Electrode spinous processes superiorly. The E-2 electrode is placed on the
scalp (see below for exact position). Irrespective of which spin
Upper Limb Montage: 4 Channels ous process is used, essentially the same potentials are observed.
I C3'/C4' FpZ'
The major negative waveform at 13 ms with superimposed 11
2 C7S FpZ'
or 12-ms, and 14-ms peaks arise from closely spaced gene~tors
3 EP (ipsilateral) EP (contralateral)
(see above) presenting with essentially the same latency from the
4 AF Olecranon
seventh to the second cervical spinous process. The amplitude of
Upper Limb Montage: 2 Channels each may vary depending upon the electrode location, with pos
I C3'/C4' EP (ipsilateral) sibly larger amplitudes recorded at C2S, as one is somewhat
2 C7S FpZ' closer to the neural generators.266.269
Lower Limb Montage: 4 Channels Scalp/lO-20 International System. The recording of corti
cal generators require the electrodes to be located on the scalp.
I CZ' FpZ' It is necessary at this juncture to examine the placement of scalp
2 TI2 or LI 4 cm superior or iliac crest electrodes as defined by the International Ten-Twenty (10
3 L3 or l4 '" cm superior or iliac crest 20) System.170.232 Approximately 10 years after the widespread
4 PF Medial knee clinical application of electroencephalography, it became obvi
Lower Limb Montage: 2 Channels ous that a standardized number of scalp recording sites were
I CZ' FpZ' necessary to promote international understanding when dis
2 TI20rli 4 cm ~Iln,""r""r or iliac crest cussing EEG pathology and possible neural generators. As a
result, the International Federation of Societies for Elec
troencephalography and Clinical Neurophysiology proposed the
electrode. Although this is a noncephalic referential montage, 10-20 system of electrode placement in 1957. 170 At the present
few far-field potentials are noted because most of the easily de time, this standard is essentially accepted throughout the world
tectable far-field SEPs are generated at or proximal to Erb's with respect to EEG electrode placements. The underlying prin
point. The waveform detected by the Erb's point electrode is a ciples governing the development of the 10-20 system are (1)
relatively large typically triphasic waveform with a prominent electrode sites are located on the scalp by using measurements
negative spike of about 10 ms (see Figs. 9-3 and 9-4). based on a percentage of the skull's size with respect to stan
Cervical Spinous Process. A single spinal electrode is usu dard landmarks (usually 10 or 20%) and not absolute distances,
ally positioned at one of several locations over the second, fifth, (2) the entire skull is represented in the system, and (3) elec
or seventh cervical spinous process and designated C2S, C5S, trode sites are labeled according to assumed cortical structures
or C7S, respectively (Table 9_3).6.7.325 These positions are easily over which the electrodes are placed. 170,232 The International 10
located by first palpating the spinous process of the seventh 20 System's true value lies in its flexibility and ease of use.
Figure 9-8. 10-20 International system. 10-20 international scalp electrode locations defining the prime designations for preferred SEP elec
trode locations. (From Nuwer MR: Recording electrode site nomenclature. J Clin Neurophysiol 1987;4: 122-133, with permission.)
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 369
Four standard landmarks are required to locate all positions Montage Recommendations. Should the practitioner have
necessary for SEP purposes. 170,232 The nasion (bridge of the the good fortune of possessing a 4-channel SEP instrument,
nose) and inion (posterior bony protuberance over the inferior each channel can record different waveforms (Table 9-3).
aspect of the occiput) are the two anatomic landmarks along the Channell may contain an E-I scalp electrode (C3' or C4') refer
skull's midsagittal plane. That region where the ears attach to enced to the midfrontal region, i.e., FpZ' (Fig. 9-3). Although
the skull, or just anterior to the tragus, form the second pair of the AES recommends FZ as the E-2 location,6.7 as previously
landmarks in the frontal plane. The ] 0-20 portion of the mea noted, FpZ' is preferred by many for ease of localization.
surement system refers to 10% and 20% of the total distance be Irrespective of location utilized, the SEP latency and to some
tween these two sets of landmarks. There is a slight difference extent amplitude should remain essentiaJly the same. One may
regarding the intent between the recording of EEGs compared aJso use the earlobe contralateral to the side of stimulation as an
with that of SEPs. Specifically, when obtaining SEPs, one E-2 site. Channel 2 may contain C3' or C4' as the E-I electrode
wishes to be as close as possible to the generators of the SEP, and the contralateraJ EP site as the E-2 electrode (Table 9-3, Fig.
i.e., the somatosensory cortex of either the upper or lower limb. 9-3). This montage is primarily used to detect far-field poten
As a result, a minor modification of the standard EEG electrode tials and will not be discussed at this time. Channel 3 is sug
locations is required to record SEPs optimally. It is necessary, gested to utilize the cervical CSS or C2S (C7S) referenced to
therefore, for those who wish to perform SEPs to become thor the scalp's FpZ'. Finally, channel 4 uses EP ipsilateral to the
oughly familiar with the 10-20 system pertinent to the recording side of stimulation as the E-l electrode while the contralateral
of SEPs (Fig. 9-8). EP serves as the E-2 electrode (Fig. 9-3). The mastoid process
Locating the optimal recording positions for upper limb SEPs may also be used as a E-2 site and may be useful for intraopera
can be performed in only a few minutes by the experienced tive studies.
practitioner. A tape measure is extended between the nasion and If an instrument with two channels is used, it is still possible
inion with the mid-point marked on the scaJp. The tape measure to obtain all the pertinent information. Recall that we are pri
is then positioned and drawn snugly between the regions where marily interested in the waveforms arising from just three
the ears join the scalp. That point at which the line extending recording sites, i.e., Erb's point, cervical spine, and somatosen
between the two ears crosses the previously defined mid-point sory cortex. Because of just two channels, one of the electrodes
of the sagittal line joining the nasion and inion designates the must perform double duty by not only acting as an E-2 elec
vertex of the skull, also called the ez electrode site (Fig. 9-8). trode, but also recording one of the desired waveforms in its
Twenty percent of the total coronal distance between the two "reference" capacity, i.e., producing an inverted response. With
ears extending from ez on this inter-ear line toward either ear two channels, the guiding principle is to use a E-2 electrode that
marks the electrode sites known as e3 and e4. Recall that odd records a waveform sufficiently displaced in time so as to not
numbers designate left-sided body electrode positions and even overlap with an E-l electrode's near-field potential. The two
numbers right-sided electrode locations; the modifier "z" indi most-displaced waveforms originate from the most physically
cates midline electrodes. 170 Therefore, C3 approximately over separated electrode locations. These are Erb's point (EP) and
lies the left and C4 the right somatosensory cortex, subserving the scaJp (C3' or C4'). Channell, therefore, uses C3'/C4' as the
the right and left upper extremities, respectively. These two E-l electrode site and EP ipsilateral to the side of stimulation as
electrode sites are standard EEG recording locations. To locate the E-2 electrode. There are two waveforms of interest on chan
the recording electrode for SEPs optimally, one must move nell; the first is an inverted Erb's point potential followed by
these two electrodes 2 cm directly posteriorly from their previ the typically appearing corticaJ potentiaJ (Fig. 9-9). As the
ously noted positions. A "prime" designation is then given to waveform recorded by EP is clearly defined, inverting its wave
these newly defined sites, such that standard upper limb scalp form should pose no difficulty in finding its peak latency.
SEP electrodes now become e3 ' and e4' (Table 9-3, Fig. 9-8). Channel 2 utilizes the standard C2S (CSS or C7S) referenced to
As previously noted, C3' and C4' are the E-l electrode record FpZ'. With this montage there are two waveforms of interest on
ing positions for the contralaterally excited median nerve. C3' is channel I, and a single waveform on channel 2 (Fig. 9-9). The
utilized for stimulation of the right upper limb nerves and C4' corticaJ potential may be somewhat larger than if a corticaJ E-2
for the left upper limb nerves. is used; however, this should not pose a problem, particularly if
The E-2 electrode is similarly located utilizing a modification side-to-side comparisons are made. A possible alternative mon
of the 10-20 system. Two midline 10-20 system electrode loca tage is C3'/C4' referenced to FpZ' on channel I and C7S to FpZ'
tions must first be located. Ten percent of the total distance be for channel 2. In this situation, if the cervical potential is
tween the nasion and inion, superior to the nasion, constitutes normaJ, the Erb's point potentiaJ may be of limited vaJue unless
an electrode site called FpZ. Twenty percent of the total dis one is particularly interested in the peripherally recorded re
tance between the above two sites, nasion and inion, from CZ sponse such as when evaluating possible brachial plexopathy or
toward the nasion designates the recording site FZ (Fig. 9-8). root avulsion.
Halfway between FpZ and FZ is the E-2 location preferred by
some investigators for SEPs and is called FpZ' .6.7 An aJternative Lower Limb Stimulation
and commonly used E-2 site is FZ. Anyone of these preceding Popliteal Fossa. In the performance of lower limb SEP stud
sites can be used for all cephalic referential recordings as it ap ies, a peripheral nerve waveform providing a "reference point"
proximates the frontal hairline and is easy to locate. Even in regarding the status of the peripheral nervous system is sug
persons with frontal balding, the former hairline is still easily gested. 6•7.232a An Erb's point recording electrode serves this pur
noted by having the patient contract the frontalis muscle. That pose in the upper limb SEP recordings ipsilateral to the side of
region of the scalp that does not "wrinkle" and is just superior stimulation. In lower limb tibial nerve SEP investigations, an E
to the frontalis muscle is about where the former frontaJ hairline 1 electrode located over the tibial nerve approximately 4 cm
was. In upper limb SEPs, therefore, C3' and C4' are referenced proximal to the popliteal crease midway between the tendons of
to FpZ' in the so-called cephalic referential montage. the semimembranous/semitendinous muscles medially and the
370 - PART II BASIC AND ADVANCED TECHNIQUES
iliac crest electrode as the reference for the same reasons previ
ously stated. It is important to note that both of these spinal elec
trodes can be used for both left and right lower limb stimulations.
It is important to recognize that the lumbosacral spine potentials
may normally be unobtainable in older or obese persons, and at
A times in healthy young individuals; hence absence of the response
should not be considered abnormal.
Scalp. An E-l electrode is attached to the scalp to record a
response from the somatosensory cortex associated with the
fibers activated in the peripheral portions of the tibial nerve, i.e.,
that portion of the cortex subserving the lower limb. The best
placement for this electrode is 2 em posterior to the vertex of
the skull (CZ) utilizing the 10-20 system and is called CZ' (Fig.
B 9_5).6.1.52.77.282 The same E-2 , FpZ', as that used for upper limb
SEP studies can also be utilized for lower limb SEP examina
tions. Because the E-l electrode (CZ') is midline and can record
the volume-conducted cortical responses from the inter-hemi
Figure 9-9. Median nerve 2-channel SEP. Waveforms recorded spheric somatosensory cortex, the same scalp montage is used
from median nerve stimulation utilizing a 2-channel instrument. for left and right tibial nerve excitation similar to the spine elec
Channel I (A) employs a non cephalic montage (C3'/C4'-EP) and dis trodes (Fig. 9-5).
plays an inverted EP potential and the expected cortical potential. Montage Recommendations. In a 4-channel recording in
Channel 2 (B) detects the cervical spine potential (C7S-FpZ'). Note strument, channel 1 is recommended to display the information
that it is possible to record all potentials of interest successfully with a obtained from CZ' referenced to FpZ' (Table 9-3, Fig. 9-5).6.7
2-channel instrument. Channel 2 can record T12S or LIS referenced to the electrode 4
cm superior to this location or the iliac crest. Channel 3 may use
tendon of biceps femoris laterally provides such a peripheral the recording of L3S or L4S referenced to the electrode placed
waveform (Fig. 9_5).1 6 •281 This electrode site is designated PF 4 em rostral to this location or the iliac crest. The fourth channel
(Table 9_3).6.7 Should any doubt exist about the proper position records the PF to medial knee waveform. In a 2-channel instru
ing of the PF electrode, an electrical stimulus delivered to the ment, it is rather difficult to obtain useful recordings from all
proper PF site results in foot plantar flexion and flexion of the four electrode positions despite various montages because of
toes. The E-2 electrode is usually placed on the medial surface electrode noise. The paraspinal muscle is particularly difficult
of the knee. to relax, but electrodes relatively close to each other help elimi
Thoracolumbar Spinous Processes. The third electrode is nate muscle artifact. Attempting to reference T12S(LIS) and
located over the third or fourth lumbar spine and referred to as L3S(L4S) to the scalp or knee may yield technically unsatisfac
L3S or L4S (Table 9-3, Fig. 9_5).6.7.52.77.282 This L3S electrode is tory recordings. The practitioner may need to record two sets of
positioned by first locating the fourth lumbar spinous process, electrodes at a time, although this will require twice the number
which is palpated midway between the iliac crests. Proceeding of stimuli. Another possibility may be to forego the PF and one
rostrally 1 spinous process allows one to locate the L3S elec of the spine sites, e.g., L3S. If the spinal potential is normal, PF
trode site rapidly. The E-2 electrode site for L3S is recom is of questionable value. Of course, if there is an abnormality in
mended to be situated over the vertebral column 4 cm superior the spinous process electrode chosen, it is then necessary to ex
to L3S. The waveform recorded from L3S permits one to calcu plore the possibility of a peripheral nerve versus plexus lesion.
late the interval between PF and L3S, yielding the conduction In this case, the needle electromyographic examination is the
time from the knee to the cauda equina region. As a result, it procedure of choice in delineating the lesion and not the SEP.
may be clinically relevant to obtain this potential in patients sus
pected of having peripheral nerve lesions. Some investigators
prefer the fourth lumbar spinous process because it is easy to SEP WAVEFORMS
locate, and this site is designated L4S. Essentially the same
waveform is observed at this location as that detected as L3S. Somatosensory evoked potentials consist of waveforms evoked
Although the above are certainly acceptable positions for the typically by an electrical stimulus applied to a peripheral nerve.
two noted electrodes, this recording tends to generate spinal wave To objectively document the integrity of the neural pathway
forms that may be rather difficult to detect because of their small under study and compare a particular potential with a reference
size. This is expected given that the two electrodes are close to data base, it is necessary to characterize the evoked potential's
gether and are rejecting common mode signals. It is the authors' waveform. Unfortunately, the manner in which the morphologic
preference to place the E-2 electrode for L3S (L4S) over the iliac characteristics of SEP waveforms are delineated is not universally
crest contralateral to the stimulated limb. 22la A somewhat larger accepted and a number of systems are currently in use. SEP
potential results without significant waveform distortion but may waveforms may be described by the following: polarity, peak
require more averages to improve the signal-ta-noise ratio. 282 nomenclature, peak latency, peak amplitude, peak-to-peak ampli
Another E-l electrode in tibial nerve recordings is located over tude, and morphology.6.1,52.91.104.105.107,250.282 As there is no consen
the twelfth spinous process and is called T12S. 6.7 Some authors sus as to how to describe waveforms, confusion with respect to
prefer to use the first lumbar vertebral spinous process (LIS) in reported waves from one investigator to the next inevitably arises.
stead of T12S. The same potential is detected at either location. It is the responsibility of the practitioner to review the pertinent
Again, the E-2 electrode is placed 4 cm rostral to this location. It literature and decide what is the most advantageous manner to
is certainly possible to also use a second or the same contralateral present the data for one's particular circumstance.
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - )71
l...o ( l f - - - - - - LN 2 - - - - - . . . . j.....:
E---LN1-.....;"'.....:
1......
, ··-r-----~2
-N1-----l-
,
,,,
··,
.
. -~----.-~-------- _____ .t.
msec
Figure 9·ID. Waveform measurement parameters. Example of recording peak latency, peak amplitUde, and peak-to-peak amplitude. The
peak latency is measured by noting the time interval between the stimulus onset and individual positive or negative waveform peaks (LN j' Lp I'
and LN2)' Peak amplitude is recorded by drawing an imaginary line through a quiet portion of the baseline to the peak ofa waveform (e.g.,AIPI)'
Peak-to-peak amplitude is calculated by identifying a particular peak, referencing it to a preceding or following peak of opposite polarity. Note that
negative deflections are above and positive deflections below the baseline, i.e., opposite to AES recommendations. (From Spehlmann R: Evoked
Potential Primer. Boston, Butterworth Publishers, 1985, with permission.)
372 - PART II BASIC AND ADVANCED TECHNIQUES
peak polarity, respectively.52,282 A number follows either the P or usually because of superimposed noise from inadequate muscle
N to signify the sequential order of peaks with the same polarity relaxation, filter settings allowing noise to contaminate the
(Fig. 9-10). For example, a waveform with an initial negative waveform's signal, not obtaining a large enough number of
potential followed by a positive potential that in tum has a repe signal averages, or some other technical problem with the in
tition of this sequence would be labeled as: Nl, PI, N2, P2. strument or electrodes. Occasionally, even after trouble shooting
Similarly, two negative peaks separated by a positive peak is and correcting the above noted problems, peak identification
designated: NI, PI, N2 (Fig. 9-10). The latency for a particular may continue to be difficult. One must initially decide if a
wave, however, is not readily apparent in this system. Also, if a waveform is present and then identify its peak.
potential's waveform for a given individual is missing, one must If there is any question as to whether a noisy tracing contains
then struggle with the sequential numbering of the remaining a true waveform, a number of options should be explored. A
peaks. recommended practice is to always perform two separate trials
A solution to this problem is attempted by designating a of each response to ensure reproducibiiity.6,7,52,282 When doubt
mean latency to be assigned to the P or N. If the negative corti remains regarding the presence or absence of a particular wave
cal waveform to median nerve wrist stimulation normally arises form, more than two averaged runs may be required to ensure a
at 20 ms, it is given the label of N20. The obvious question then waveform's existence. Other trouble shooting measures include
is, what do you call this potential if it occurs at 30 ms?52.282 performing several averaged trials without the delivery of a
Should it be referred to as "N20 occurring at 30 ms," N201N30, stimulus. An averaged trace obtained in the absence of a stimu
or simply N30? lus provides a good idea of the background noise. By compar
The system used by a growing number of investigators and ing averaged traces with and without stimulation, it may be
that recommended by the AES is a combination of all of the easier to appreciate which waveform peaks are noise compared
above proposals. 6 •7 The capital letters P and N continue to be with a true physiologic response. At times it may be helpful to
used for polarity. The characteristic or mean latency of appear contrast SEP trials recorded with a weak stimulus with those
ance for a specific peak latency is reported with a bar or line obtained utilizing a stronger excitation pulse. A recording with
drawn over the latency value. When this potential is abnormal, a weak stimulus should produce smaller waveforms, thereby en
the mean peak latency is followed by the observed latency.91 suring the presence of a possible peak in the stronger stimulus'
This is the so-called observed versus characteristic nomencla trace. This is a variation on the theme of delivering no stimulus
ture. For example, if the median nerve's cortical SEP is ob at all.
served at 30 ms, it is designated as: N20 occurring at 30 ms or Should the above methods fail to remove sufficient doubt re
N201N30. A simple way in which to report these data in an SEP garding a peak's presence, it is also possible to include a period
report is to designate a data column as N20 and place 30 ms in of time prior to the activation impulse's delivery to assess the
this column thereby assigning the recorded latency to a charac two regions of the trace with respect to noise versus stimulus
teristic waveform. related artifact. 195 Another way to attempt to eliminate stimulus
AES Recommendations. For those previously derived related events contaminating the desired waveform is to
upper and lower limb montages noted above for the median and alternate the polarity of the stimulator during data coIlec
tibial nerves, the AES6.7 recommends a number of specific des tion. 262 ,263.312 This option may result in a slightly different la
ignations for particular recording locations. In median nerve tency because of the several-centimeter difference between the
SEP studies, channel I 's C3'/C4' to FpZ' yields a major cortical two stimulus sites. One or a combination of several of the above
waveform with the designation N20. Channel 3's cervical spine techniques should convince the practitioner of the waveform's
(C2, C5, or C7) to '!:pZ' resul~in waveforms with the peak des true nature. It is also possible for the stimulus to generate suffi
ignations NIl, Nl3 and Nl4 or Nll1N13. The Erb's point cient artifact to interfere with the SEP waveform. Rotating the
recording on channel 4 remains EP and is not given a specific anode about the cathode can at times optimize the initial aspect
letter and number abbreviation. Some authors, however, refer to of the recording that is influenced by the stimulus artifact.
this potential as N9 or NlO.4,130 A difficulty often encountered in attempting to identify an
In tibial nerve SEP investigations, the popliteal fossa, third SEP peak arises in a particularly noisy tracing in which there
lumbar, and twelfth thoracic recording locations are simply re are several minor deflections of similar amplitude superimposed
ferred to by their anatomic designations as PF, L3, and TI2 p0 on a major waveform. There are four recommended methods
tentials, respectively. Letter and number assignments are one may use to assist in the identification of a peak's latency
provided for the cortically detected waveforms. The first se (Fig. 9-11).282 Let us suppose that a major SEP waveform is
quential positive/negative waveform is referred to as P37 and contaminated by sufficient noise to result in two small peaks su
N45, respectively. perimposed on a major waveform despite all attempts to mini
mize this noise. The first manner in which to arrive at a peak
PEAK LATENCY latency is simply to identify the peak with the highest amplitude
and assume that this is the primary SEP peak had noise been
Identifying a waveform's peak is obviously important, as this eliminated. A second option is to pick the first peak irrespective
is the manner in which normalcy is decided with respect to la of the subsequent peaks identified. Thirdly, the time difference
tency. Under optimal conditions, the peak of an SEP waveform of the two peaks can be split such that a point midway between
is noted as the time from the stimulus onset to the region of the the two peaks is chosen and identified as the waveform's la
maximum positive or negative sequential peak deflections (Fig. tency. Should more than two peaks appear, the difference be
9-10). In SEP studies, the instrument's latency markers begin tween the two furthest separated peaks may be chosen. The
measuring time from stimulus onset to where the practitioner fourth venue extends the slopes of the first and last minor peaks
locates the time marker on the waveform. Although this is usu above the major waveform using the point of intersection as the
ally not a problem, it can be rather difficult at times to decide peak latency for the SEP (Fig. 9-11). Of course, none of these
exactly where the waveform's peak occurs. This difficulty is measures are ideal but they are practical solutions to a difficult
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 371
lesion affects the peripheral nerve conveying the electrical im in accurately measuring the distance along the arm and central
pulse at some point distal to, or at, the Erb's point record conduction routes as well as latency delays along syn
ing. 52 •282 Also, the cervical and cortical potentials could be apses.6.7.52.104.282 Spehlmann282 has delineated general guidelines
expected to be delayed a similar amount, as the impulse cannot to help the beginner interpret the multichannel recordings with
make up the time lost peripherally in the central nervous respect to possible lesion location or instrumentation errors that
system. The interpeak latency or central conduction time be may mimic neural pathology (Table 9-4). .
tween the cervical and cortical regions as reflected by their re A similar line of reasoning to that noted above can be applied
spective interpeak latencies can be anticipated to be normal, to lower limb SEPs. The PF waveform serves as the marker for
eliminating the possibility of a centrallesion. 36 Should the EP peripheral nerve function. The latency between PF and L3
potential be normal but the cervical Nl3 potential be delayed or allows one to assess the conduction across the sacral plexus and
absent, a lesion most likely exists between the brachial plexus cauda equina. An interpeak time from L3 to Tt2 provides insight
and the posterior columns at the cervical spine where NO is into impulse propagation from the cauda equina to the entry of
generated.2&2 Also, the cortical potential would be expected to the lower aspects of the central nervous system. Central conduc
be abnormal, as the lesion is "down stream" from the scalp elec tion can be evaluated by subtracting the TI2 latency from the
trode, which reflects all previous slowing. If the N13 potential is cortical P37 peak latency. If a Tt2 potential is not recorded, the
delayed but present, the interpeak latency between the cervical L3 potential can be utilized for similar purposes. The presence,
region and the cortex would be normal, although the absolute absence, or delay of the above noted potentials can yield infor
N20 potential might be delayed. Finally, a normal EP and cervi mation regarding possible lesions affecting different aspects of
cal spine potential but abnormal scalp potential suggests a the somatosensory conduction pathway (Table 9-5).282
lesion in the somatosensory pathway rostral to the dorsal
columns in the neck, possibly involving the brain stem, thala AMPLITUDE MEASUREMENT
mus, thalamocortical radiations, or the cortex itself. 52.2&2 One
may measure conduction velocities along the somatosensory In addition to peak latency, an SEP's amplitude is also an im
pathway simply by dividing the distance between recording portant parameter to evaluate with respect to normalcy and com
sites by the interpeak latencies. However, the accuracy of such parative side-to-side measurements. The amplitude of an SEP
conduction velocities are limited by the difficulty encountered represents the magnitude of the potential difference between the
two recording electrodes and depends upon the individual mon It may be necessary to determine a "zero" baseline if the initial
tage utilized. As previously noted, the location of the two peak arises immediately from the preceding baseline (see
recording electrodes directly influences the amplitude of the above). Alternatively, the descending limb of the potential can
recorded potential. For comparison studies in individual pa be assessed by measuring the vertical displacement of a particu
tients, the same recording montage must be used to minimize lar peak with a negative to positive descent (Fig. 9-10). Finally,
the technical factors causing amplitude variation. In addition, a third option is to calculate both the ascending and descending
the criteria used (base-to-peak or peak-to-peak) should remain limbs of a peak and determine the mean of both sides of the po
consistent. Although not accepted by all investigators, side-to tential. Of course, there are difficulties with this method if a
side amplitude differences of 50% or more are considered in large peak is preceded by a smaller peak that does not achieve a
dicative of a possible abnormality. It must be recognized, prior zero baseline level. An additional objection raised to this
however, that normal persons can have considerable side-to-side method of quantifying SEP amplitudes is based upon the theo
amplitude differences, approaching 80% or more. 102 Unfor retical consideration of each peak being the result of a neural
tunately, there is no universally accepted manner in which to de generator. Measuring from one peak to the next may be combin
termine the magnitude of various waveforms. Thus, it is ing information from two different generators. The amplitude,
imperative that one standard method of amplitude determina therefore, is not representative of one group of neurons, but a
tion be chosen and the reference data for that montage used. mixture of neurons possibly from different locations. This type
Adhering to a particular recording methodology also allows the of amplitude measurement may be "mixing apples and or
practitioner to gain confidence in the method and experience in anges",2 and not representative of a true loss of neurons from a
optimizing the waveforms in either normal or pathologic situa particular site in pathologic states. Despite the theoretical objec
tions. Two widely used amplitude measurement schemes are tion, this method is recommended in assessing SEP amplitudes
presented: peak amplitude and peak-to-peak amplitude. 52•282 because it is rather easy to perform and is useful for subsequent
follow-up studies, particularly when performed by different ex
Peak Amplitude aminers. It is the authors' observation that novice practitioners
In order to evaluate an individual waveform with the "peak have less difficulty in identifying sequential peaks to calculate
amplitude" method, a reference "zero level" is required. This SEP magnitudes compared with defining a horizontal zero line
relative "zero" potential can be determined in a number of ways. from which to measure an amplitude.
Once the SEP is averaged, the practitioner can subjectively
assess what appears to be a flat horizontal baseline running WAVEFORM MORPHOLOGY
through the entire recording and designate this line as the "zero"
reference point. One may also select a relatively "quiet" time Many of the SEP waveforms for both upper and lower limbs,
period devoid of any waveforms either preceding or following including spinal potentials, have characteristic shapes. Normal
the SEP component waveforms and declare this the reference variations and subtlety of difference between normal waveforms
baseline. 282 Whatever method is used, the SEP's amplitude is and those found in pathologic situations preclude a simple ref
measured with respect to the ordained baseline signifying zero erence analysis based solely on shape. Although there has been
potential. The amplitude of an individual peak is then defined as an attempt at classifying SEP waveforms with respect to normal
the maximum vertical displacement above the zero line as mea and abnormal morphologic parameters,105,107,1ll.250 this method
sured by the instrument's amplitude marker (Fig. 9-10). ology is not widely accepted. 52,282 As a result, the shape of SEP
Specifically, one of the markers is placed on the declared zero waveforms is not heavily weighed in the criteria to decide if a
line, while the other is located on the identified SEP peak. The particular waveform should be described as abnormal.
instrument then displays the vertical displacement above the
zero line in appropriate units, i.e., microvolts. This method
works quite well for SEP recordings with very stable baselines. SEP INSTRUMENTATION
Difficulty arises, however, when the trace is rather noisy, sev
eral sequential waveforms are superimposed on each other, or MINIMAL STANDARDS
the time period preceding or following the waveform is erratic.
It is also somewhat challenging to measure peak amplitudes ac The fundamental aspects of instrumentation pertinent to the
curately if the responses are particularly small and a "wavy" recording of SEPs are essentially the same as those used for
baseline is present. Fortunately, an alternative method of assess needle electromyography and nerve conduction studies (see
ing waveform amplitudes is available. Chapter 3), with a few alterations. Minimal criteria regarding
instrumentation parameters as defined by the AES are stated in
Peak·to·Peak Amplitude this section to further clarify the instrument's specific require
Evaluating SEP's waveform with respect to amplitude by ments to obtain optimal SEP recordings free of distortion. 6•7A
using the peak-to-peak method is somewhat easier than the peak number of exceptions to the general AES guidelines for all
amplitude method discussed above. 52.282 Simply, the peak-to types of evoked potentials are delineated and personal prefer
peak amplitude is the vertical displacement of the instrument's ences are detailed. Recording parameters should be identical to
amplitude markers when placed between the maxima of consec those used for collection of reference data whenever possible,
utive SEP peaks of opposite polarity. Depending upon the wave
form's peak morphology and the practitioner's preference, there Amplifier
are a number of methods by which to calculate the peak-to-peak The minimum differential input impedance must be at least
amplitude. It is possible to place one of the instrument's ampli 10 MO, and the input signal's magnitude should be capable of
tude markers on the first positive or negative peak and the sub being amplified between 1000 and 500,000 times. 6•7,52.282 A
sequent peak of opposite polarity. This allows one to calculate common mode rejection ratio of least 10,000: 1 (80 dB) at the
the amplitude of the ascending limb of the potential (Fig. 9-10), instrument's greatest sensitivity is desirable. Multiple filter settings
376 - PART II BASIC AND ADVANCED TECHNIQUES
capable of creating a wide bandpass of 0.1 Hz to 5000 Hz are intervals the digitizer can sample, just as the horizontal (time)
suggested. Of course, the filter settings for individual SEP stud resolution is dependent upon the number of horizontal digital
ies will vary with the parameters used by the individual investi data points. The vertical resolution is defined by the number of
gator. When utilizing the above open bandpass, the instrument's vertical intervals available for the amplitude at each horizontal
inherent noise level should not exceed 3 1ly'320 data point interval. The vertical string of bits is referred to as a
word. Therefore, an 8-bit converter is an AID converter with a
Averager word length of 8 bits. An 8-bit binary number represents 28, or
The AES recommends that an averager's time (horizontal) 256 points of vertical resolution for each horizontal data point.
resolution be at least 80 Ils/data point/channel with a minimum An 8-bit digitizer has a total vertical range of 256 independent
of 250 resolution points per channel. The amplitude (vertical) voltage levels. The total number of intervals is one less than the
resolution corresponds to at least an 8-bit converter, and the number of levels, i.e., there is one interval between levels I and
maximum number of averages per waveform must meet or 2. The resolution, therefore, is 1 vertical interval out of a total of
exceed 4000 trials should circumstances warrantP The mini 255 intervals, or 0.39% of a waveform's amplitude.
mum number of channels is determined by the type of evoked The practitioner must decide on the number of stimuli to be
potentials performed. averaged for a particular SEP waveform. Although most instru
Exception is taken to these AES recommendations. Although ments have the capability of performing several thousand con
such specifications may be appropriate for auditory evoked po secutive averages, the waveform's signal-to-noise ratio
tentials given the time period of waveform production (about 8 improves only by the square root of the number of averages (see
ms or less for all waveforms), they are inappropriate for SEP Chapter 3). Thus after averaging a few hundred responses, the
studies. For example, consider the minimum requirements marginal improvement in the signal-to-noise ratio is of ques
noted above of 250 data points combined with a resolution of tionable benefit given the amount of time necessary to collect
80 lls/point/channel. These resolution parameters allow only additional data. For example, to double the signal-to-noise ratio
for a total screen analysis time of 20 ms, which is barely following 100 averages, one would need to acquire 400 sweeps.
enough to perform upper limb SEPs (i.e., 80 J1s1point/channel x To again double the signal-to-noise ratio, 1600 sweeps would
250 points = 20,000 J1s/channel =20 ms/channel), and com be necessary, and so on. Several thousand averages can also be
pletely unacceptable for lower limb SEPs. Given that lower quite time consuming. An SEP waveform is typically optimized
limb SEPs need about 100 ms total analysis time, an instru by averaging 300-500 times and performing two separate trials
ment's resolution is supposedly inadequate at 400 J1s/data point of 300-500 averages. Two trials of 500 averages is considered
(100 ms1250 points/channel = I msl2.5 points/channel 400 more reliable than one trial of 1000 averages because it verifies
Ils/point/channel). the various waveform parameters.
The authors recommend the instrument have a minimum of
250 data points of horizontal resolution for a screen time of 100 Display
ms, yielding a time resolution of 400 J1s/data point/channel. A An additional minimal instrument requirement is for some
resolution of 400 J1s/data point equates to a resolution or sam type of ongoing CRT display. The CRT should have amplitude
pli;.g frequency of 2500 Hz (1 data point/400 J.ls =2500 data and time scales that can readily be interpreted. It is also neces
points/lOOO ms = 2500 Hz). The highest frequency likely to be sary for a hard-copy of the averaged waveform to be printed out
encountered in most SEP studies is the rise time of the EP or PF and maintained in the patient's records for future reference. b.?
potential, which in the authors' opinion is less than 800 Hz. As
the given parameters of 250 data points over lOOms and 400 DESIRABLE INSTRUMENT OPTIONS
J1s/data point produce a resolution at least 3.1 times the EPIPF
rise time, these potentials should be adequately resolved. The The above instrumentation features are those minimally nec
spinal and cortical waveforms occur over much longer time peri essary to perform reasonable SEP analysis. There are, however,
ods than the EP/PF potentials and should be resolved without a number of additional instrumentation parameters that may
difficulty. Recall that at least two points of resolution are re enhance data acquisition and flexibility in difficult recording
quired to minimally resolve a waveform (Nyqvist frequency),282 conditions.
and in the above worst-case scenario, at least 3.1 points of reso
lution (2500 Hz/800 Hz = 3.1) are available. A resolution is pre Amplifier
ferred of 200 J.ls/data point for lower limb SEPs and 100 J1s1data Certainly, the greater the common mode rejection, the quieter
point (10,000 Hz) for upper limb SEPs, i.e., 100 ms/500 data the recordings, particularly in electrically noisy environments. 6•7
pointslchannel (lower limb) and 50 ms/500 data points/channel It is also helpful for the amplifier to have the capability of inter
(upper limb), or a total of 500 data points per channel. The above nally switching electrode montages and quickly measuring the
explanation deals with the minimum requirements to just resolve electrodes' impedances. From time-to-time, it may be appropri
any SEP waveform. If your instrument can produce a higher res ate to verify the calibration of the instrument, and an internal
olution of 80 lls/data point/channel, more than enough resolution device to check the calibration on the CRT screen is helpful.
is present to optimally resolve the waveform in question.
With respect to amplitude, an 8-bit analog-to-digital converter Averager
(AID converter or digitizer) is recommended. 6 ,7.282 In digital in Horizontal resolutions in excess of 500 points per channel
struments (all presently available commercial instruments), the and vertical resolutions of 10 bits or higher will improve the
digitizer samples the original analog signal at a fixed frequency. digital reproduction of the original analog signal. Variable
Each sample is converted into a digital representation of ampli sweep analysis times from 5 ms to 100 ms provide the practi
tude, i.e., a binary number. This amplitude then consists of a tioner with flexibility regarding the performance of less routine
number of binary digits or bits. The vertical resolution of the SEP studies and allow one the capability of expanding into
signal's amplitude is dependent upon the number of vertical other types of evoked potential work. A nice feature is to be able
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 377
to store the previously recorded wavefonns for on-screen com difference between the two recording electrodes, this difference
parisons between multiple traces from the same and other is amplified and can obscure the biologic signal. This is why it
sites. 6•7 A preset counter with the capability of ending data col is important, if at all possible, that the two recording electrodes
lection after a designated number of averages are acquired is for any given channel be of the same material. When the two
also a convenience. electrodes are constructed of the same metal, the bias potentials
It is helpful to exclude responses contaminated with large ar developed at their surfaces are more likely to be similar, thereby
tifacts that may continue to distort the final SEP wavefonn de allowing the instrument to eliminate the same bias potentials
spite multiple averages. An automatic artifact reject option through common mode rejection through the process of differ
accomplishes this by pennitting one to set the amplitude voltage ential amplification. When the E-l and E-2 electrode are dis
criteria beyond which a potential is not included in the averaged similar metals, different bias potentials can develop at each
response. When using an automatic reject option, care must be surface, resulting in a potential difference that is dissimilar and
exercised to not set the voltage criteria too stringently, as arti subsequently amplified. Additionally, dissimilar electrodes may
fact-free responses may also be excluded. If the instrument is have different impedances, resulting in the recording of slightly
including only a few traces to be averaged, the voltage exclu different common signals, e.g., 6O-Hz interference, thereby am
sion criteria set on the automatic reject option should be plifying this difference. This impedance mismatch results in the
checked and the environment investigated for excess noise, and recording, instead of elimination, of 60-Hz noise. The above
all electrode leads examined for discontinuity. One must also statements suggest that it is not a good practice to mix surface
consider a particularly noisy environment or a bad electrode and needle recording electrodes. Metals that are relatively pure
lead introducing excess noise into the system in such cases. and can be kept free of surface contamination are the materials
Particularly noisy traces can be improved somewhat with re of choice for electrode manufacture. Such metals are silver,
spect to mUltiple minor irregularities in the baseline by using a gold, tin, platinum, and stainless steel and considered ideal sub
so called smoothing filter. 282 This is a rather simple technique stances from which to construct electrodes because of the fol
whereby the data represented by 3 or 5 digital resolution points lowing considerations: cost, availability in pure fonn, ability to
are averaged to yield one data point. This process is repeated se resist oxidation, and minimal tissue toxicity. Gold is usually
quentially, thus reducing the small irregularities in the trace. preferred over silver for surface electrodes because it resists en
The net result is to "smooth" out the final appearance of the vironmental degradation due to oxidation and tarnishes consid
trace. This option should be used judiciously because it may erably less. 138 With respect to needle electrodes, the preferred
alter the SEP shape, amplitude, and inter-peak latency relation materials are stainless steel or platinum mixed with another
ships. Some instruments provide the practitioner the option of metal so that the needles are good conductors, and strong yet
adding or subtracting wavefonns from one channel to that of an flexible enough to penetrate tough tissues such as the scalp.
other. Finally, the ability to adjust when the collection of data Pure gold is too malleable to be used in needles.
by the averager begins with respect to the stimulus may be of
assistance in some cases, Le., data collection is delayed until the RECORDING ELECTRODES
stimulus artifact has subsided. Other options are offered by
manufacturers, but the practitioner must clearly explore how Surface Electrodes
such features will be of benefit in particular clinical settings in The most common electrodes used for recording SEPs are
relation to the additional cost to the overall unit. those typically used for EEG recordings. 52,282 These surface
electrodes are a 4-10 mm metal cup with a hole in the center
and a flat rim. A relatively long (24-48 inches) insulated wire
ELECTRODES serves as the lead that connects the metal cup to the instrument's
amplifier port. After selecting the site from which to record (10
Electrodes utilized for the detection of SEPs may be classi 20 system or other landmarks noted above), one of the most
fied into recording and stimulating electrodes. Both can be challenging aspects to novice practitioners is the optimal secur
either needle or surface electrodes. Again, there are no stan ing of electrodes to the patient.
dards regarding the particular material an electrode must con Prior to attaching surface electrodes to the patient, it is first
tain, and the type of electrode and its method of application are necessary to prepare the skin site adequately. Recall that the
primarily left to the practitioner. Because of this flexibility, one SEP potential is relatively small compared with the background
must be aware of various technical aspects regarding the multi EEG potentials, muscle activity, and other environmental noise.
ple electrodes available. As a result, the electrode must be secured to the patient such
that it is capable of optimally contacting the patient's electrolyte
COMPOSITION volume conductor conveying the various biologic signals of in
terest. This can be achieved only if the superficial layers of the
Essentially, an electrode serves the function as an intennedi skin are adequately abraded, allowing the electrolyte paste
ary between the instrument and the biologic signal of interest placed within the electrode's cupped surface to be in contact
within the body and may be defined as: " ... a metallic connec with the patient's electrolytic solution. When this contact is
tion between the complex physiological electrolyte of tissue and achieved by all electrodes, the signal of interest is recorded and
the recording circuitry."13S Recall from Chapter 3 that the noise is eliminated. It is possible to know when the electrode
metal/electrolyte interface can result in a transfer of ions be patient interface is ideal by measuring the impedance through
tween the recording electrode's metal surface and the body's two such prepared electrodes.
ionic solution, giving rise to potentials (bias potentials) at the Recall that resistance is the difficulty a current encounters in
two electrodes possibly resulting in rather large potential differ an attempt to move through a conducting medium. Resistance is
ences between the two electrodes.138 If the two electrodes are used the tenn used when dealing with direct currents but is replaced
for recording minute biologic signals and there is a measurable with the tenn impedance if alternating currents are encountered
178 - PART II BASIC AND ADVANCED TECHNIQUES
(see Chapter 3). In biologic systems, the hindrance to current stylus and applying collodian around the electrodes' rim. The
flow is discussed utilizing the concept of impedance. When de drying of collodian is hastened by blowing compressed air over
scribing the electrode-patient contact, the hindrance of flow the site or using a hair dryer.52 Once the electrode is securely in
across this interface is known as impedance. The impedance is place. it is filled with electrolyte cream through the central
clinically measured by passing a weak alternating current of a hole. Following completion of the study, the collodian is re
specified frequency through the amplifier across both recording moved by dissolving it with acetone. 137 As these materials (ace
electrodes or between each electrode and ground, and calculat tone and collodian) are volatile, adequate ventilation is
ing the magnitude of impedance to this current. It follows that if mandatory and explosion precautions must be taken. Of course,
there is minimal impedance to an impressed current flow by the all of the collodian is rarely removed and the patient should be
instrument. any currents or differences of voltage in the body instructed that several shampooings may be necessary before
passing by the electrode will also enter the instrument. If the the collodian is no longer present.
impedance is high as determined by the instrument, then most
likely. current will also not flow from the patient into the ampli Needle Electrodes
fier. Remember that current prefers the path of least resistance. As previously noted, stainless steel and platinum alloy subder
A low inter-electrode impedance provides an accessible current mal EEG needles are commercially available for SEP studies. The
path into the instrument. High inter-electrode impedance cre main rationale for using needle electrodes is primarily ease of ap
ates a situation in which the current continues to flow in the plication. 137•138,282 Subdermal needle electrodes should be placed at
body's lower impedance, instead of entering a pathway of the appropriate site just under the skin so as to enter the patient's
greater impedance, i.e., across the skin and into the instrument. electrolytic solution conveying the biologic signals. Because the
When applying surface electrodes, an alcohol swab rubbed volume conductor has been entered, the skin site does not need to
across the skin followed by a commercially available pumice is be prepared to reduce the impedance. A local antiseptic wipe is
used to abrade the skin site gently by removing several superfi used, however, prior to penetrating the skin. The elimination of
ciallayers of the skin and skin oils. It is generally accepted that skin preparation considerably reduces the time necessary to place
abrasion is considered sufficient when the impedance measured mUltiple electrodes onto the patient. Unfortunately, needle elec
across two such electrode preparation sites is between 1000 and trodes are subject to being pulled out easily. It is recommended
5000 ohms (Q).52,282 When the impedance is less than 1000 Q, that some slack be placed on the electrodes' lead wires prior to
care must be taken to avoid a situation in which the amplifier is taping them to a portion of the body such that an inadvertent pull
short-circuited through aberrant conduction pathways such as on the wire does not remove the needle.
excess perspiration or electrolyte paste between two electrodes.
In this instance, the impedance through the abnormal conduct COMPARISON OF NEEDLE AND SURFACE ELECTRODES
ing pathway is less than through the electrodes and the current
(biologic signal) would rather travel the path of least imped The impedance of needle electrodes is measured in the same
ance, thereby bypassing the instrument. If the impedance manner as that for surface electrodes. It is important to realize
through the electrode-patient interface is significantly greater that needle electrodes can have higher impedances than surface
than 5000 Q (approaching 10,000 Q or more),less biologic cur electrodes. 52•loo This may seem like a contradiction when one
rent enters the instrument and the recorded signal is attenuated. considers that the needle penetrates the skin and does not have
When abrading the patient's skin, it is important to inform the to contend with the impedance of the skin. Actually, the imped
patient of the mild discomfort about to be experienced and the ance of the surface electrodes are lower than that of the needle
development of a red and tender area about the electrode site. primarily because of the metal from which they are constructed
This area of skin may be uncomfortable for a few days, particu and the amount of exposed surface area, as well as a dipole
larly when bathing. A scab may also form over the site. The layer that forms about the electrode. That is, the impedance of
patent should be directed to treat this as a superficial wound and gold or silver is lower than stainless steel or platinum. Also, the
keep it clean and dry until healed. surface area of the needle is considerably less than that of the
Surface electrodes can be secured to patients in essentially one surface electrode, which produces an elevation in the imped
of two ways, depending upon the anticipated duration of the ance. Once the skin is abraded sufficiently, an impedance of
study. For relatively short investigations, 1-2 hours, an electrolyte 2000 Q can easily be achieved with surface electrodes. Needle
paste fills the cup aspect of the electrode and it is firmly pressed electrodes usually have impedances greater than 3000 .Q and
onto the prepared skin. A cotton ball may be placed on top of the can even reach 10,000-13,000 Q (personal observation). As
electrode to prevent the paste from drying out and allow a larger long as the input impedance of the amplifier is 10 MQ or more,
contact surface, compared with the electrode, to which tape can the higher needle impedance does not alter the signal apprecia
apply a counterpressure. Enough tape should be used to permit bly because it is in direct contact with the body's volume con
mild traction on the electrode lead and yet prevent electrode slip ductor. This is quite different than surface electrodes. When the
page. It is a good practice to allow a small amount of electrode impedance is much higher than 5000 Q for the surface elec
lead slack by taping the electrode's wire to some portion of the trode, the biologic signal is no longer reaching the surface elec
patient. This prevents the electrode from being dislodged should trode because it cannot cross the skin barrier. The needle
the wire be tugged on accidentally. Although the use of elec electrode, however, is below the skin and in contact with the bi
trolyte cream and tape is rather time efficient, this method is po ologic signal. In this instance, even though the impedance is
tentially subject to more recording and mechanical artifacts. comparatively larger than surface electrodes, the biologic signal
In the event that a period longer than 1-2 hours should be is not lost to the needle electrode because of the high amplifier
necessary, a more satisfactory method of applying electrodes is input impedance (see Chapter 3).
required. The skin site is first prepared as noted above to A number of standard textbooks on SEPs state that caution
reduce impedance. A cup electrode with a hole in the center is needs to be exercised when using needle electrodes because of
secured to the patient by holding it in place with some type of the risk of infection, discomfort, higher electrical noise. and
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 379
ease of pulling OUt.52.119.282 The supposed elevated risk of infec studies is preferred by these authors. In other regions of the
tion compared with surface electrodes has not been documented body such as Erb's point, popliteal fossa, and spinous processes,
to the authors' knowledge in either short- or long-term studies. the risk of movement or other potential complications must be
On the contrary, with the placement of needle electrodes into the weighed. As discretion at times is the better part of valor, sur
scalp of normal subjects for approximately 4 hours, no signs of face electrodes may be the most appropriate type to use in these
dermal infection were noted for a follow-up period of 1 week. loo regions, simply to avoid the possibility of complications. The
Concerns regarding contamination with the human immunodefi application of a needle electrode about the popliteal fossa may
ciency virus and the hepatitis virus are similar for both needle be appropriate, but one must be aware of the possibility of the
and surface electrodes. Recall that the impedance for surface patient flexing the knee. Should this occur while the needle is
electrodes must be reduced, and this is accomplished by abrad positioned such that a neural or vascular structure may be punc
ing the skin sufficiently to expose the patient's volume conduc tured, obvious repercussions might ensue. Similar concerns can
tor to the metal electrode. It is difficult to reduce the skin's be expressed for inserting a needle electrode in the interspinous
impedance optimally without also producing some flow of space to record spinal potentials. It is the authors' preference to
serum or possibly blood byproducts, thereby contaminating the use needle electrodes only on the scalp and place surface cup
surface electrodes similar to needle electrodes. Any recommen electrodes at all other recording locations. The difficulty of se
dations suggesting that only soap and water are necessary for curing electrodes to the scalp is significantly greater than that of
cleansing surface electrodes while more stringent practices are placement on nonhairy body regions. With practice, applying
somehow necessary for needle electrodes appear contradictory. surface electrodes to nonscalp regions can become rather easy
Once a study is over, the electrode should be carefully cleaned. and avoids possible complications noted above with the use of
A surface electrode should have the paste removed by gently needle electrodes to these same locations.
cleansing it with mild soap and warm water to remove debris
before the electrolyte dries. This electrode should then be prop STIMULATING ELECTRODES
erly sterilized per the Centers for Disease Control and Prevention
instructions. 43 •44 Needle electrodes can be handled similarly by Essentially any type of electrode, surface or needle, routinely
placing them in bleach for about 15 minutes and then steam-au used in nerve conduction studies can also be used to activate the
toclaving them. Any electrode, surface or needle, potentially ex peripheral nerve in SEP investigations.282 The major require
posed to Jakob-Creutzfeldt disease or other possible slow virus ment is to accurately locate the electrode over the appropriate
disorders should be safely and immediately discarded. 126 peripheral nerve or dermatome to be excited. Surface electrodes
Commercially available disposable needle electrodes have re may be placed over a peripheral nerve following a mild cleans
cently become available similar to disposable electromyographic ing of the skin. The degree of skin abrasion required to reduce
needles, and satisfactory recordings can be achieved. the impedance for recording sites is not necessary for the stimu
Needle electrodes may actually be more comfortable (per lus site. If t-m inordinate amount of current is used to excite a
sonal experience) than surface electrodes, as the skin does not nerve properly and the patient complains of discomfort, one
have to be abraded.loo.138 In the only study to compare scalp should first consider repositioning the electrode to optimize the
recorded SEPs utilizing surface and needle electrodes, no statis cathode over the nerve. Continued difficulty in exciting the
tically significant difference was detected between waveform nerve may be due to elevated skin impedance hindering current
latency and amplitude. 1OO Both recordings were satisfactory re from reaching the nerve. The skin may need to be abraded
garding artifacts. The conclusion that needle recordings are elec somewhat to reduce the impedance to current flow in an attempt
trically inferior to surface recordings is simply inaccurate. As to reach the nerve's depth within the tissue. When using needle
noted previously, securing the electrode's lead wire to the patient electrodes to activate a peripheral nerve, the usual caution of
will prevent inadvertent removal during the study. Gloves should near-nerve placement without piercing the nerve should be
be worn at all times when performing any study in which one taken into consideration. A needle electrode requires less cur
may be exposed to serum, blood, or its constituents. rent duration than surface electrodes, typically 50 J.lS compared
with 200 J.ls, because the needle is placed only a short distance
TYPE OF ELECTRODE APPLICATION from the nerve and does not need to "push" current across the
high-impedance barrier of the skin.
The question may arise as to which type of electrode-needle
or surface-is optimal for a specific recording location. As one STIMULATION AND GROUND ELECTRODE
might anticipate, there are no universally agreed upon stan CONSIDERATIONS
dards. Simply, one may consider this issue with respect to the
potential electrode site. That is, the placement of an electrode Stimulus Isolation/Grounding Considerations. It is recom
may be scalp or nonscalp. Additionally, if the anticipated elec mended that all stimulus units be isolated from ground.96.98.224.265
trode location is covered with hair, one may expect that secur This is easily accomplished by using a transformer in which the
ing the electrode may be difficult should one wish to not use induced current does not have a physical pathway to enter the in
coUodian. A final consideration might be the amount of poten strument. Isolating the stimulator assists in minimizing stimulus
tial movement across a particular body segment. artifact from interfering with the SEP waveform and also pro
As the scalp is usually a hairy region, the use of subdermal tects the patient from aberrant current flow. Fortunately, the
needle electrodes is an ideal consideration for ease of applica commercial standard for stimulating units utilize the concept of
tion and removal as well as patient comfort.loo.l38 Appropriate isolating the stimulator from ground.
taping ensures the successful completion of the study. Time The use of a ground electrode reduces unwanted current flows
consuming impedance reduction, possibly messy electrolyte and helps produce technically optimal recordings. The skin place
creams, and the taping of hair are avoided. The use of needle ment site should be abraded just as for the E-l and E-2 elec
electrodes for all scalp locations when performing routine SEP trodeS. 224 The ground, usually a large metal plate or circumferential
380 - PART II BASIC AND ADVANCED TECHNIQUES
band electrode, should be positioned between the B-1 electrode and signal with 60-Hz interference and average this noise into the
the stimulating electrodes.'}6·98,224 SEP response. For these reasons, stimulation rates of 5.1 or 2.8,
Stimulus Characteristics. A stimulus pulse of 200-300 IlS for example, are frequently used.
duration is preferred for most mixed nerve SEP investiga Suboptimal stimulus delivery may result in delayed cortical
tions.52.282 The stimulus intensity utilizing the above pulse width potentials of reduced amplitude or altered morphology.52.282
should produce a visible twitch of a muscle innervated by the Increasing the stimulus intensity, current or pulse duration, pro
excited mixed peripheral nerve. A moderately vigorous twitch is duces a normalization of the SEP parameters. Too Iowa stimulus
desirable, provided it does not cause the patient intolerable dis may not activate the large and fastest conducting nerve fibers (IA
comfortP The patient should feel a strong tapping and possibly afferents) but instead only excites the slower group II afferents or
a sensation of muscle contraction but not overt pain. Decreasing only a portion of the relatively slower spectrum of group IA affer
the skin impedance through mild dermal abrasion results in the ents. These slower conducting fibers take longer to reach the
need for less current and, therefore, less pain production. If sig cortex (delayed arrival), and hence may yield a comparably dif
nificant adipose tissue overlies the nerve, needle stimulation ferent appearing potential (smaller amplitude and unexpected
may be indicated. When using needle electrodes for stimulation, morphology). Although one might infer that the quality of the
the stimulus duration should be reduced to 50 J.1S or less to avoid stimulus can be objectively evaluated by observing the peripheral
neural damage, as one no longer needs a long duration to acti SEP marker potentials at EP and PF for amplitude and/or latency,
vate the nerve optimally.238 In the event that a pure sensory this unfortunately is not always true. A peripheral neuropathy
nerve or dermatome as opposed to a mixed nerve is studied, the may produce delayed or reduced amplitUde potentials that may
stimulus intensity is adjusted to 2.5-3.5 times the sensory appear quite similar to delivering a weak stimulus. A good judge
threshold. 10.11 1.1 84. IS5 Sensory threshold is defined as the current of an adequate stimulus for mixed nerve studies is observing an
intensity when the patient first describes a sensation resulting adequate muscle twitch. When performing pure sensory studies
from the stimulating pulse. Raising the current intensity to in patients with altered sensation, one may still attempt to deliver
2.5-3.5 times this value, given patient tolerance, should suffice between 2.5 and 3.5 times the sensory threshold. If this stimulus
in producing a clearly defined sensory SEP.1O·184.185 fails because of patient discomfort, increasing the stimulus inten
As previously stated, the SEP has a rather small amplitude and sity to a mild discomfort level and then reducing the current until
is easily obscured by background noise requiring large numbers a tolerable pulse is delivered can be tried. Of course, caution must
of averages. The process of data collection can take a significant always be exercised in patients with altered sensation.
amount of time. For example, 1000 averages delivered at 2 Hz re Additionally, higher intensities of stimulation may activate other
quires approximately 8 minutes to collect a response. This time structures, such as nearby mixed nerves, which could produce an
must be doubled if one is to perform two trials. Studying multiple erroneously normal response. Although one can use bilateral
nerves can take quite a long time at the above pace. It is, there stimulation to investigate the nervous system, unilateral excita
fore, desirable to increase the delivery rate of the stimulus in an tion of one nerve at a time is usually the best method to elucidate
attempt to decrease the time per examination. Unfortunately, the location of a lesion affecting a peripheral or central portion of
there are limits of how fast an exciting pulse can be delivered the nervous system. Bilateral stimulation may be used to observe
before there is a noticeable deterioration in the waveform. In the for a spinal potential during SEP intraoperative monitoring if uni
upper limb, the optimal stimulus rate is no more than 5 Hz; in the lateral stimulation does not generate a SEP.226
lower limb, this limit approaches 2-3 Hz.52.282 Although the phys Stimulator Type. Most commercially available instruments
iologic mechanism underlying these stimulation limits with re provide the practitioner with the option of using either constant
spect to waveform reproduction is unclear, one can certainly current or constant voltage stimulation. Although either may be
understand how too fast a stimulus adversely affects waveform used, a constant current stimulator is preferable because one is
resolution from purely an instrumentation standpoint. In the assured, within reason, that the same amount of stimulus is de
upper limb, an analysis time of 50 ms is typically used. livered with each pulse over time even if the impedance under
Specifically, the waveform requires 50 ms to show all of its com the stimulating electrodes change secondary to electrochemical
ponents on the CRT screen. If one delivers a stimulus prior to the effects between the metal-electrolyte-skin interface. Also, when
complete resolution of the previous potential, there is an overlap measuring side-to-side stimulus thresholds for either mixed or
of waveforms with mutual cancellation of positive and negative pure sensory studies, it is much easier to quantify the amount of
waveforms leading to significant latency and morphology alter current delivered for the duration of the study.
ation. For an analysis time of 50 ms, the theoretically maximum Typical current intensities vary between 5 rnA and 15 rnA,
rate of stimulus delivery is approximately 20 Hz (1 potential/50 depending upon the impedance between the electrodes and un
ms x 1000 msll sec = 20/sec or 20 Hz). In the lower limb, an derlying nervous tissue.282 Should the patient have a peripheral
analysis time of 100 ms is used, yielding a maximum pulse deliv neuropathy or other pathology affecting the peripheral nervous
=
ery of to Hz (l/l00 ms x 1000 ms/l sec to lsec or to Hz). The system, the utilization of longer stimulus pulse durations ap
physiologic limitations are considerably below this instrumenta proaching 500 IlS and higher amperage may be necessary. It is
tion limit. Long latency cortical potentials, greater than 50 ms advisable in such circumstances of altered pain perception to in
(upper limb), are known to follow peripheral nerve stimulation. crease the current judiciously.
The interaction of these potentials with short latency responses
from a previous stimuli may possibly reduce the theoretical upper
limits of stimulation into or below the above noted ranges. In both REFERENCE DATA AND CRITERIA
upper and lower limb investigations, the rate of stimulation FOR ABNORMALITY
should not be an integral of 60 Hz so as to minimize recording
this common environmental noise. Remember that the stimulus Optimal interpretation of SEP information depends directly
rate initiates the CRT sweep and averager. If the stimulus rate is upon a reliable reference data base. The validity of utilizing
divisible into 60, it may be possible to simulate a time-locked reference data is based upon the investigator's skill and technical
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 381
30r---~~-------r~~~~~----~--~--'-~~~
•; 25
~ ~-:~~±:::~~~~~-:~~~~;:~;:~!~s:~":"~:~g"=::·:·:.:
...... 24
.i
~
23
22
a:.. 21
1." 20
- 19
18
17
16 ................. ::::::;:::::=-.,::::.H........ I······.. ·.·.····........-'-........ __
...
.........i.......................+......................
15 ----~~~-- __~~~~~__~__~~~~__~~~____~~
140 150 110 170 180 UIO 200
A Relabt (....)
Figure 9-12. L I reference data Graphic plot of absolute latency to the II spinous process recording electrode with respect to patients'
height for posterior tibial nerve stimulation at the ankle. (From Chiappa KH: Evoked Potentials in Clinical Medicine. New York. Raven Press, 1997,
with permission.)
expertise. All beginning practitioners should develop their ref which to judge patient results. To produce valid means and stan
erence values for the commonly performed procedures if fea dard deviations, the distribution of the recorded reference data
sible. Prior to accumulating this information, it is acceptable base must be determined. If the sample is large enough and sta
to use another laboratory's published reference values if at tistical analysis reveals a normal gaussian (bell-shaped) curve,
least 20 individuals were used with age ranges comparable the standard deviation and means can be directly calculated.6,7.52
with patients examined by the practitioner and identical instru On the other hand, if normal values from SEPs, particularly
mentation parameters and technique are employed. small sample sizes, do not yield gaussian distributions, it is nec
essary to transform these data to a more normal or gaussian dis
SUBJECT SELECTION tribution through the use of various transformation functions
such as square root, logarithms, or reciprocals before determin
To develop a reference data base for an individual laboratory, ing means and standard deviations. 52 Two and one-half standard
it is critical to select an appropriate population of subjects. A deviations about the mean (98%) of the population tested is
careful family and personal history must be taken prior to in often used to represent "normal data," while a number of labo
cluding an individuaI.6.7.52.282 Ifthere is any suspicion of possible ratories utilize 3.0 standard deviations about the mean (99.5%
nerve pathology, it is best to exclude that person from the of the population tested}.6.7.52 Using only 2.0 or less standard de
"normal popUlation." It is also recommended that a complete viations is considered inappropriate by most investigators, since
history for any type of drug use (legal or illicit) be pursued, as an unacceptably high number of false-positive results will be
such use may adversely affect the SEP results. obtained. When applying standard deviations about the mean,
An ideal control population should contain a comparable one may occasionally note that a non-sensical negative number
number of age-matched males and females. In children and can be obtained, e.g., 3.0 ± 1.9. In this example, 2 standard de
adults, age-specific normal values should be determined by viations below the mean is -0.8 ms, which occurs because of
decade, including the eighth and ninth if possible. For infants, the nongaussian distribution of the data.
reference data are obtained by months, while the perinatal
period requires reference values based on weeks.58-60 Optimally,
each subgroup should contain at least 20 individuals. One FACTORS AFFECTING THE SEP
author suggests that prior to performing any SEP, one must ex
amine a minimum of 35 control individuals and use the same PATIENT COOPERATION
parameters on suspected abnormal persons. 52
One of the most important and often forgotten issues in per
ABNORMAL CRITERIA forming SEPs is the patient's understanding of, and subsequent
ability to participate in, the examination. The SEP study is often
Initially, the pool of normal values obtained must be statisti a new experience for the patient. He or she may enter the study
cally analyzed to determine a mean and standard deviation from with some level of fear and anxiety. An anxious or uncomfortable
382 - PART II BASIC AND ADVANCED TECHNIQUES
person cannot optimally participate in the study. Frequently, an not necessary.52,242.m,m Of course, should one of these agents
SEP evaluation may last one or more hours, and the patient's be used, precautions must be given to the patient regarding the
cooperation is perhaps the most crucial portion of the investiga operation of a motor vehicle or performing any activity requir
tion. Nervous patients often produce significant conscious and ing mental alertness.
unconscious muscle contractions. The electrical activity from
these contracting muscles can completely obliterate even rela PATIENT HEIGHT
tively large normal responses. Relaxation is often the key to a
successful study. One of the best ways to gain an individual's When performing lower limb SEP studies, it is important to
complete cooperation is to explain fully, in terms the patient can record the patient's height. As one might anticipate, the conduc
understand, what is about to be done and why. It is often possi tion time for tibial nerve stimulation, for example, from the
ble to visually observe a patient's facial countenance and body medial malleolus to the cortex, is longer for a comparably tall
posture relax once the individual comprehends the SEP test and than short person because of the increased length of both the pe
experiences its benign nature following the first few stimuli. It ripheral and central conduction pathways. The patient's height
is advisable to then re-zero the averager's stimulus counter at is used as a correction factor for more meaningful latencies
this point and begin data collection without interrupting the when comparing scalp, spinal, or central conduction times.
rhythm of stimulation. Graphic plots 51 (Figs. 9-12, 9-13, and 9-14) and regression
To assist in the above goal of patient cooperation and relax equations (see below) are available to assist in the determina
ation, the appearance of the room must not be underestimated. tion of reference peripheral and central peak latencies to correct
A relatively quiet, temperature-controlled, and attractively dec for height. When considering central conduction times for
orated room with neatly aligned electrodes and other equipment median nerve excitation, N13 to N20 inter-peak latency, there
conveys a professional and organized atmosphere. The patient's appears to be little correlation with arm length or height. 53 ,159,223
plinth should be comfortable, with clean bed sheets and multi Apparently, the central conduction pathway from the cervical
ple pillows. Prior to connecting the electrodes, the patient spinal cord to the cortex is relatively the same in tall and short
should be offered the opportunity to use the lavatory because individuals. The lumbar N20 to cortical P37 (P40 as designated
the test can be quite lengthy. Following the placement of elec by some authors) inter-peak latency (central conduction time)
trodes, the supine position should not be the only one consid for tibial nerve stimulation, however, is correlated with an indi
ered. It is reasonable for the patient to assume whatever is the vidual's height (Fig. 9_14).52.53
most comfortable position, provided it does not compromise the
recording of SEP potentials. In the authors' opinion, a com AGE
pletely relaxed but not asleep patient is desirable. The patient is
asked to keep track of the stimuli in some manner that is not Multiple investigations using different methodologies produce
mentally taxing, but promotes a subdued level of alertness. The conflicting results regarding the influence of age on various
use of mild hypnotics such as chloral hydrate or diphenhy SEP parameters. The affect of age on SEP cortical amplitude
dramine is recommended by some investigators, but this is usually suggests that there is a "U"-shaped curve in that infants and
to 41
....!I= 31
40
..,to- 38
~ 37
II; 38
35
34
33
32
31
30
140 150 HID 180 110 200
A
Figure 9-13. Scalp reference data: Tibial nerve. Graphic plot of absolute scalp latencies (P37) follOWing tibial nerve stimulation at the
ankle correlated with patient height. (From Chiappa KH: Evoked Potentials in Clinical Medicine, New York, Raven Press, 1997, with permission.)
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 383
25
. i . i i ... , i . i .
24 ·······-··LP-!NlP-37···¢oniluet~oD···!J!im,le····vs··:-Helght·........
......II• 20
::~;;;;:1",,::,,·=,,";+~t~::::,,]:·:·:~~t~~
21
......a 19
0
~i-j:~:~~?iii=~;:I~S~;-~~;;:f;-~~=f
0
=' 18
'U
a0
u 17
.,
~
At
18
.......
II: 15
I
~ 14 - - - . - - - - - - - - - - - - - - . - - - . : . . . . . . . . . . . . . . . . . . . . . . . . - ' ; - - - • • • • __ • • • • • • • • • • • • __ . :___ . . . . . . ___ . . . . . . . n • • • • ' ; _ • • • • • • • • _ - . - . . . . --.-.---r----~----.---- . ---..-.
~::=::~j=~:=:i=~-=-:t=:::::=r·;::;::=+=
13
12
11 j......... ........
··················~····t························t····: .... ~ .............. ~:::.! -j-...:..................""\"...:..................
Figure 9-14. Central conduction time: Tibial nerve. Graphic plot of central conduction times (P37-Ll) for tibial nerve stimulation at the
ankle correlated with height. (From Chiappa KH: Evoked Potentials in Clinical Medicine. New York, Raven Press, 1997, with permission.)
children display larger amplitudes than young and middle-aged central nervous system following tibial nerve stimulation has
adults. 57,162,2os,274 This last group, however, has smaller ampli only once been studied in depth. lSI This investigation examined
tudes than persons older than 40 years. 162 Spinal SEP potentials the conduction times along the spinal cord segment and the por
demonstrate a different pattern. In infants, the lumbar and more tion between the neck and cortex. Both segments demonstrated
rostral spinal potentials were larger than those recorded in chil slowing of conduction velocity with age. Intra-cortical conduc
dren and adultsY The cervical spinal N13 potential is similar tion time as measured by cortical inter-peak latencies e.g.,
for subjects between the ages of 10 and 39 years, but then dis N20-P22 or P37-N45, has been shown to increase with ageSO,20S
plays a steady amplitude decline for those of 40 years and as well as demonstrate no change. ISO A final consensus regard
greater. 163 The reason for these amplitude findings is unknown ing the effects of aging on central conduction is not yet at hand,
but may be related to the extent of myelination in childhood and but there appears to be a small central conduction velocity de
selective fiber loss with aging.103 cline in persons over 60 years of age.
Unlike age-related amplitude effects, the correlation between
age and conduction time (conduction velocity) is less clear. GENDER
There is agreement that the peripheral nervous system initially
demonstrates slow conduction velocities until about 4 or 5 years A few studies have attempted to compare SEP waveforms be
of age, at which time adult values are achieved. 19,127,300 Adult tween men and women, There is a consistent prolongation of
SEP conduction values are usually achieved between 5 and 8 potential latencies in men. 162,164 The increase is most likely a
years of age. The central conduction time characteristics with result of body stature, as men demonstrate statistically signifi
respect to age are less straightforward. The majority of studies cant height differences compared with women,4,53,223 The central
have focused on the time of conduction between the cervical conduction time appears to bear no relationship to the gender of
Nl3 to cortical N20 potentials following median nerve stimula the subject. I Several studies suggest that the SEP amplitudes,
tion. Several studies investigating a wide range of ages found however, are slightly larger in women, but more work is needed
that although the peripheral nerve conduction velocity slowed to substantiate these findings. 53,'64 At the present time, it seems
with increasing age, the central conduction time remained con acceptable to pool both latencies and amplitudes from men and
stant.223,333 A larger number of investigations, however, found women when developing reference data bases as long as a pop
that not only did the peripheral nerve conduction velocity slow, ulation representative of various heights is included.
but so did the central conduction velocity.4,5,93,'62"s,,290,292 One
study comparing central conduction time in younger and older TEMPERATURE
individuals found that in a population with a mean age of 31,6 ±
14.1 years, the central conduction velocity was 55,8 ± 12.1 mls Temperature is an important factor affecting nerve conduc
compared with 42.4 ± 13.1 mls for persons 74.1 ± 7.5 years. 93 tion velocity. Because the upper and lower limbs consist of sig
Another group of investigators found the central conduction nificantly less mass than the trunk, they are more prone to
time increased 0.3 ms/yr for persons between the ages of 50 and fluctuations in temperature with respect to the environment
60 years. 162 The central conduction time along the length of the under routine laboratory conditions, As a major portion of the
384 - PART II BASIC AND ADVANCED TECHNIQUES
somatosensory pathway consists of the peripheral nervous Central conduction times are also prolonged. When performing
system, and is, therefore, subject to temperature variations, it is intraoperative SEP monitoring, the avoidance of these agents
important to be cognizant of temperature's role in altering SEPs. has been recommended. I IS These effects are countered by em
A cool limb, particularly digits when performing segmental or ploying a balanced anesthesia technique that uses a strong nar
dermatomal investigations, may prolong the anticipated laten cotic in addition to a muscle relaxant plus a weak anesthetic like
cies to all SEP peaks. Although a room temperature of 20-22°C nitrous oxide,226 or low concentrations of isoflurane. The pre
is recommended,52,282 it is the authors' opinion that this precau ceding approach appears to provide the necessary anesthesia
tion by no means guarantees an acceptably warm limb. The sur without significantly compromising SEP recordings.
face temperature of the upper limb at or proximal to the site of
nerve stimulation should be maintained at 32°C or more, while SLEEP
the lower limb should be approximately 30°C or higher, This
can be accomplished with hot packs, radiant warmers, or other The ideal SEP should be free of artifact, especially that aris
means. Of course, if a laboratory has standardized its data at a ing from muscle, to produce clearly defined peaks so that laten
particular body temperature, then by all means this is the tem cies can be easily defined. Unfortunately, waveform
perature at which the data should be collected. Use of interpeak contamination from muscle electrical activity is frequently en
latencies subtracts out peripheral slowing due to cooling of the countered even in apparently relaxed patients. Attempts to cir
limbs and can be employed when it is not practical to warm the cumvent this interference by encouraging the patient to sleep
limbs. can alter waveform morphology and latency. Stage II sleep may
Central core temperature is subject to less fluctuation with re result in up to a 2.4-ms prolongation of latency in the wave
spect to emotional or environmental conditions. Studies investi forms obtained in tibial nerve SEP studies. 326 In general, sleep
gating the effects of central temperature modulation on SEP tends to reduce the amplitude and increase the latencies of
morphology or latency are limited in number. In one upper limb recorded SEPs. Sleep has been shown to reduce the amplitude
SEP study, the investigators elevated the central temperature of of dermatomal SEPs or abolish the responses altogether, and
subjects by 1°C and noted that the N13 potential's absolute la hence should be avoided when performing these studies,30 It is
tency decreased by 0.7 ms, the N19latency decreased by LO preferable to have the patients relax in the supine position but
ms, and the Erb's point potential was reduced by 0.18 ms.217 On maintain a level of alertness. This can be accomplished by
the other hand, a second investigation considered the effects of asking the patient to clench and relax the mandible several times
temperature on SEPs by measuring latencies in patients with in succession so as to be aware of how to relax these muscles.
fevers (38,0-39,7°C) and again following fever resolution,187 Additionally, this same maneuver is performed with the
No significant latency changes were noted in these patients. In frontalis and paraspinal muscles. Once the patient is aware of
cancer patients receiving whole body hyperthermia up to core these muscles and what they feel like in the relaxed state, it is
temperatures of 42°C, an absence of cortical SEPs occurred. 95 often possible to reduce muscle artifact dramatically and obtain
Whether this SEP disappearance is a result of peripheral nerve relatively quiet recordings. The patient is also asked to just be
or central pathway conduction failure is unclear. Patients receiv peripherally aware of the stimulus and make a mental note of
ing hypothermia for intractable seizure control with core tem the stimulus delivery without actually counting the number, thus
peratures lowered to 29°C demonstrated a cortical SEP latency maintaining some level of alertness. Also, encouraging the pa
prolongation and amplitude reduction.285 Again, these may be tient to fix his or her gaze or gently close the eyes can limit as
central or peripheral effects. sociated external ocular muscle artifact.
MEDICATION REPRODUCIBILITY
Although it is generally believed that medication in ambula Any technique used to diagnose a possible neural lesion must
tory patients has little effect on SEP latency, amplitude, or mor be reliable and reproducible. Unfortunately, the reliability and
phology, the relationship between various drugs and SEPs has reproducibility of SEP potentials have not been investigated
not been extensively studied. Phenobarbital in therapeutic systematically or extensively. A few anecdotal reports note that
dosages does not appear to alter the central conduction time in the SEP latencies did not reveal statistically significant changes
comatose patients,84,142,143 In cats, therapeutic levels of pentobar over time within the same patients. 29,218,310 There is a need for
bital also does not effect SEPs.291 Utilizing auditory evoked po large studies examining the variation of latencies and ampli
tentials, phenytoin has been shown to increase inter-peak tudes within the same subjects and between different individu
conduction times. 143,144 These effects were not noted for primi als over time.
done or carbamazepine, Diazepam has been recommended to One study examined spinal responses in both healthy persons
reduce muscle artifact, thereby improving SEP recordings, but and in individuals with spinal cord injuries and head injuries. 29
these authors did not report the results of latencies between sub An average test/retest period of 16.2 months demonstrated that
jects who received the drug and those who did not. 242 Should di the spinal potentials were very stable with respect to amplitude
azepam cause a patient to sleep, one may then anticipate a and latency in all groups examined. Correlation coefficients of
number of SEP changes (see below). 0.84 and 0,78 for controls and patients, respectively, were found.
The largest group of patients who have been studied with re Additional studies are needed to corroborate these results.
spect to SEP medication effects are those undergoing surgery
and who receive a general anesthetic. Essentially, the volatile
agents in high concentrations such as the halogenated hydrocar SEP TECHNIQUES
bon inhalation agents (halothane, enflurane, and isoflurane)
produce an increase in cortical potential latencies in addition to This section of the chapter is by no means meant to be an ex
a reduction in cortical potential amplitudes. 94 ,236,237.241,259,260,319 haustive litany of the multiple techniques available to elicit
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 385
SEPs. The major upper and lower limb mixed and pure sensory and the palmaris longus medially. Although it is convenient to
nerve SEP methods are described and accompanied by available place a bar electrode, cathode proximal (anode at the level of
published reference data. Although there is controversy regard the distal wrist crease), between these two tendons, separate
ing some SEP methodologies with respect to clinical applicabil disk electrodes can also be used. A bar electrode is convenient
ity, these concerns are not discussed at this time. but examined because it is easy to firmly secure this electrode combination in
in detail in later sections of the book dealing with the diagnosis place. It is a good idea to abrade the stimulation site gently with
of specific disorders. It is important for the beginner to realize an alcohol swab prior to electrode placement with adequate
that compared with nerve conduction and needle electromyo conduction paste. The impedance is usually not recorded for the
graphic techniques, diagnostic SEPs are relatively new. As a stimulation site because all that is required is submaximal nerve
result, fundamental questions relating to neural generators, vari excitation. The stimulus usually consists of a pulse duration of
ability of latencies and amplitudes, reference data, appropriate 200 J.1s delivered at 5.1 Hz or less at an intensity necessary to
applications, and other important issues remain. These knowl produce a moderately vigorous thumb twitch. 6,7,52,77
edge gaps result in multiple gray areas directly affecting diag Ground Electrode. The ground electrode should be located
nostic decisions. Tolerance for the unknown as well as a between the stimulating electrodes and the first recording elec
willingness to err on the conservative side in diagnosing pathol trodes to yield optimal waveforms. This implies that when per
ogy is mandatory when performing SEPs. forming bilateral studies, it becomes necessary to relocate the
ground electrode. It is often possible to place the ground elec
UPPER LIMB SEPS trode in the midline, for example, on the sternum or forehead.
and still record clear SEPs. Should artifact be a problem, the
Upper limb SEP techniques may be divided into three pri ground electrode may be moved to the limb between the stimu
mary categories. The first major group of studies consists of lus and recording electrodes.
stimulating a mixed peripheral nerve and recording both pe Recording Electrodes. When the median nerve is investi
ripheral and central (spinal and scalp) waveforms. Multiple gated. the placement of electrodes is usually standard as de
studies have examined the most appropriate manner in which scribed below; however, the manner in which they are
to elicit these potentials and their clinical utility. Additionally, connected to the instrument varies with the number of channels
these waveforms are relatively large and easy to obtain by the available. It is possible to obtain the necessary data with either a
novice. The second category of upper limb SEPs pertains to 4- or 2-channel instrument. The methods for utilizing both types
pure sensory nerves and are occasionally referred to as seg of instruments and electrode placement are described below.
mental SEPs. Segmental studies primarily involve the excita Erb's Point. An electrode is secured just superior to the mid
tion of a major sensory nerve composed of fibers originating portion of the clavicle, 2-3 cm superior to the bone where the
from primarily one nerve root innervating the site of stimula clavicular head of the sternocleidomastoid muscle inserts. The
tion. The third category of upper limb SEPs is dermatomal peripheral nerve volley is recorded as it traverses the brachial
SEPs, which do not involve stimulation of a nerve trunk. but plexus beneath the electrode. 6,7,177 It is a good idea to perform
rather an area of skin subserved by a given dermatome. These left/right comparisons. In a 4-channel recording, the fourth
latter two techniques are performed with the goal of recording channel records the Erb's point potential ipsilateral to the side
only from the scalp, as the peripheral and spinal potentials are of stimulation, while the opposite Erb's point electrode is uti
extremely small and often lost in the surrounding muscle and lized as the E-2 electrode. 6,7,77 In a 2-channel recording, the
environmental noise. As one would anticipate given this infor Erb's point electrode is the E-2 electrode for channel 2. The E-l
mation, a check on the peripheral nervous system is needed. electrode placed in channel I is noted below.
Peripheral nerve status can be determined through mixed nerve Cervical Spine (C2, C5, C7). The cervical spine location
SEP studies, segmental or dermatomal SEPs, or routine nerve functions as a marker from which to measure the central con
conduction velocity determinations. duction time. There are three acceptable locations for the cervi
cal electrode: over the C2, C5, or C7 spinous processes. These
MIXED NERVE SEPS three locations yield essentially the same latencies, although the
C2 region may result in slightly larger amplitudes compared
For the purposes of this discussion, a mixed nerve is defined with the other two locations. In both 2- and 4-channel record
as a major branch of the peripheral nervous system containing ing, the cervical electrode is connected to the E-l port. while
both motor and sensory fibers.33o The afferent pool of nerve FpZ' serves as the E-2 electrode. 6,7.77
fibers excited convey not only cutaneous sensation but also Scalp. Scalp electrodes record cortical SEP waveforms and
those fibers relaying information from the large muscle spindle utilize the international 10-20 system for the C3' and C4' elec
afferents. In the upper limb. two mixed nerves are typically ex trode positions.46,47,J70,232 In the 4-channel system, the first chan
cited to produce SEPs. The median and ulnar nerves are rela nel contains C3'(left) or C4'(right) referenced to FpZ'.6,7.52,282
tively easy to stimulate and result in large and reliable SEP This scalp montage should routinely yield relatively large and
waveforms from both the peripheral and central nervous sys noise-free cortical recordings. If a 2-channel system is used, the
tems. The median nerve usually produces slightly larger poten C3' or C4' electrode is placed in the E-l port of channel 1 and
tials than the ulnar nerve,n.329 as one might anticipate given its the Erb's point electrode serves as the E-2 electrode. Because
fiber content and larger cortical representation. 22 ,134,330 the Erb's point potential occurs at approximately 10 ms, while
the C3'/C4' potential is not recorded until approximately 20 ms,
Median Nerve there is no difficulty in recording both of these two potentials on
Stimulation. When performing mixed nerve SEP studies for the same channel. Of course, the Erb's point potential is in
the median nerve, one typically places the stimulating elec verted compared with its E-l port location in other montages,
trodes over the median nerve at the wriSt.5~77,174 The nerve is lo but its latency remains essentially unchanged, as does the side
cated between the tendons of the flexor carpi radialis laterally to-side amplitude comparisons for this technique (Fig. 9-9).
386 - PART II BASIC AND ADVANCED TECHNIQUES
Table 9-6. Mean Central Conduction Time (ms) used to detect far-field potentials. This is accomplished by plac
Mean CCT SD ing C3' or C4' into the E-l channel and using the contralateral
Erb's point electrode as the E-2 electrode. 6,7,52 Any other re
5.6 0.5 159
sponse the investigator is interested in examining can also be
5.6 0.6293 placed into the fourth channel. Obviously, if a 2-channel instru
5.5 0.7 106 ment is utilized, simultaneous optional recordings are limite.d.
5.7 0.6 130
Instrument Parameters. The most important aspect regard
ing instrumentation parameters is that the conditions under
5.7 0.5 302 which the reference data were originally acquired must be repro
5.7 0.5 161 duced. The performance of upper limb SEPs requires an analysis
5.3 0.5 278 time of about 50 ms, which is accomplished by a sweep speed of
5 ms/div. This total analysis time may need to be increased by 10
5.8 0.8258
ms or more with severe lesions. Filter setting of 10Hz to 3000
5.8 0.64 Hz are adequate to include the major subcomponent frequencies
5.5 0,4176 contained in the waveforms while simultaneously limiting noise.
5.1 0.9 324 A final signal amplification of about 2 11V/div usually results in a
0,4312
waveform contained on the CRT screen, but occasionally, more
5,4
or less sensitivity may be required. Depending upon the size of
5.9 0.5 39 the SEP and the background noise, between 300-500 and 1000
The central conduction time refers to the interpeak latency between N 13 and averages are sufficient to resolve most SEPs. At least two trials
N19. should be performed for each recording site. 6,7,52.282
Modified from Cant BR, Shaw NA: Central somatosensory conduction time: Reference Data. As previously noted, it is a good idea for
Method and clinical applications. In Cracco RQ, Bodis-Wollnar I (eds): Evoked
Potentials. New York, Alan R. Liss Inc., 1986, pp 58--67.
each individual to perform sufficient SEPs to obtain a reference
data base. This information should then be compared with pub
lished values. Multi~ studies have been published on the cen
Alternate Recordings. In the above-noted electrode loca tral conduction (N13-N20 latency) demonstrating a mean
tions, the 4-channel instrument has one remaining channel that conduction time of 5.6 ms (Table 9_6).112,113,160,257,293 Regression
is not utilized. This open channel can be used to monitor a equations are also available to account for height and age.223
number of other responses. It is possible to detect the median Regarding a regression equation for the EP potential latency,
nerve's peripheral response distal to the brachial plexus by one finds EP = 0.086H + 0.038A - 5.88 for men and EP =
recording at the antecubital fossa. 77 An E-l recording electrode 0.054H + O.03A - 0.59 for women, where H is the subject's
is placed on a point half-way between the medial and lateral height in centimeters and A is the age in years. An equation de
humeral epicondyles medial to the biceps brachii tendon. An E scribing an N13 latency for men is N13 = 0.099H + 0.045A
2 electrode is then located over the ulnar nerve or the olecranon 4.98, while female latencies can be described as N13 = O.064H +
process. As previously noted, the second channel can also be 0.035A + 0.78. A cortical N191atency for men can be arrived at
Ulnar Nerve
Stimulation. The ulnar nerve at the wrist can be readily
activated either just medial or lateral to the tendon of the
A flexor carpi ulnaris. Similar to the median nerve, the anode is
placed at the level of the distal wrist crease, while the cathode
is located several centimeters proximal to this site. A bar elec
trode is convenient. Gentle skin abrasion with an alcohol
EP Ni3
swab may be of assistance in reducing the current intensity
needed to excite the nerve and reduce patient discomfort. A
stimulus pulse with a duration of 200 Jls, rate of 5 Hz or less,
B and an intensity capable of producing a moderately vigorous
but nonpainful twitch of the abductor digiti minimi is usually
employed. 52.77.282
Ground. The general rule of placing the ground electrode
between the stimulating electrodes and first set of recording
electrodes should be followed. One may also wish to locate the
ground electrode in the midline on the sternum or forehead if
the level of background noise or stimulus artifact permits.
Figure 9·15. Ulnar nerve SEP. Ulnar nerve SEP utilizing a 2-chan Recording Electrodes. Similar practices as those utilized
nel technique. Note the inverted EP potential preceding the cortical for the median nerve also apply to the mixed ulnar nerve stud
response on channel I (A). The second channel (B) records the NTI ies. As always, the more channels an instrument has, the more
potential with a C7S-FpZ' montage. flexible one can be regarding how the channels are connected to
the recording sites. Identical recording sites are used for the
ulnar nerve as those for the median nerve (see above).
by using Nl9 = O.095H + 0.049A + 1.19, and for women the Erb's Point. Essentially the same type of preparation and lo
=
equation is N19 0.085H + O.043A + 2.72. The equations de cation site as that used for the median nerve are recommended.
scribe a gender difference for SEP latencies, but not all authors Because the ulnar nerve tends to produce a waveform with a
agree that gender results in a significant difference for SEP arrival slightly smaller amplitude than that obtained for the median
times. These regression equations provide expected mean values; nerve, meticulous technique is suggested. In a 4-channel instru
limits of normal depend upon the standard deviation for each ment, the E-l Erb's point electrode is referenced to Erb's point
variable. A number of investigators' reference data are included contralateral to the side of stimulation.6.7 For a 2-channel instru
for the reader to compare reproducibility between reputable labo ment, the Erb's point electrode is used as the E-2 electrode for
ratories and for technique verification purposes (Table 9-7). This channell (see median nerve) (Fig. 9-15).
table consists of data from individuals with varied heights and Cervical Spine (C2, C5, C7). Either C2S, C5S, or C7S can
ages, although the specific parameters of these persons are not be used for recording the spinal potential. With 4 channels. the
always provided. Thus, the regression equations may be of value. E-l cervical spine electrode is referenced to the forehead site,
i.e. FpZ'. In a 2-channel setup, the second channel contains the intensity is slowly increased until the patient first notes the tin
E-l cervical spine electrode, also referenced to FpZ'. gling sensation produced by the stimulating electrodes, which
Scalp. Again, the international 10-20 system is utilized to usually occurs at approximately 3-4 mA.184.185,282 This defines
place the cortical electrodes in proximity to the somatosensory the patient's sensory threshold. The stimulus intensity is then
cortex by using the C3' or C4' recording sites as for the median slowly increased to between 2 and 3 times the individual's sen
nerve. 170.232 With 4 channels, either C3' or C4' is referenced to sory threshold, which approximates 6-12 mAo If the patient
FpZ'. A 2-channel instrument requires the appropriate cortical cannot tolerate this excitation, it is decreased until a strong but
electrode to be placed into the E-l amplifier port of channel 1 tolerable pulse is delivered. Of course, if the patient is hyper
using the contralateral Erb's point electrode as the E-2 (Fig. 9 sensitive and the current is insufficient to generate maximal
15). In the 2-channel instrument. the rationale for which the SEPs, the study becomes invaJid because insufficient current in
electrodes are connected to the amplifier is the same as that for tensities result in low amplitude and delayed potentiaJs.52.282 As
the median nerve. previously noted, a constant current stimulator is preferred be
Alternate Recordings. If one has the lUXUry of 4 channels, cause this enables the practitioner to easily quantify the amount
all channels can be used. The mixed nerve action potential from of current delivered to ensure proper neural excitation with each
the ulnar nerve can be recorded by placing an E-l electrode over pulse during the study.
the ulnar nerve in the ulnar groove with an E-2 electrode located Three digits can be analyzed when performing median nerve
anteriorly between the humeral epicondyles. This is the reverse segmental studies.77.129,264,297 Ring electrodes are located on any
of the electrode orientation noted above for median nerve of the first three digits of the hand. Although some authors rec
recordings. Of course, the fourth channel can simply be turned ommended a 4-cm separation between cathode (proximal) and
off as welL anode,17 this really is not necessary for stimulation. 297 The ring
Instrument Parameters. The same parameters used for the electrodes used are the same when obtaining antidromic median
median nerve are employed. Because of the comparatively sensory nerve action potentials. The electrodes should be placed
smaller ulnar nerve amplitudes, the practitioner should be pre such that the opening of the ring's noose is located posteriorly,
pared to increase the amplifier's sensitivity. thereby maximizing contact of the cathode and anode with the
Reference Data. The ulnar nerve has not been as extensively median nerve on the volar aspect of the digit. Recall that the
studied as the median nerve. A number of investigators' pub radial nerve innervates the dorsum of the finger and is not the
lished normal values are provided to assist the reader in per nerve to be excited at this time.
forming these studies as well as to provide reference values to Ground. Because of segmental SEPs' small amplitude,
compare one's own reference data (Table 9_8).52.77.129 meticulous electrode placement is critical. It should be placed
proximal to the recording electrode. This position will vary de
SEGMENTAL SENSORY NERVE SEPS pending upon the placement of the recording electrodes. As de
scribed below, only cortical electrodes are performed and,
Somatosensory evoked potentiaJs arising from the excitation therefore, the ground is positioned on the mid-frontal region of
of sensory nerves as opposed to mixed nerves can also be the skull or on the sternum.
recorded. One can preferentially activate a peripheral sensory Recording Electrodes. The number of recording electrodes
nerve, e.g., superficiaJ radiaP7 (segmentaJ stimulation), or a por used and their location are dependent upon the particular tech
tion of the skin innervated by a nerve at a more distal site, e.g., nique. The relatively small amplitude of the segmental SEP can
lateral aspect of the foot (S-I dermatomal stimulation).184.185 render the Erb's point and cervical spine sites somewhat difficult
Generally, segmental stimulation results in more easily obtain to record. Although it is by no means impossible to obtain these
able and somewhat larger responses than dermatomal SEPs, as responses,297 there is little margin for error and meticulous tech
more nerve fibers are excited. Compared with mixed nerves, nique combined with a relaxed patient is needed. Cortical poten
few studies have documented in a controlled manner either tials, on the other hand, are significantly less difficult to record
normal values or the utility of pure sensory SEPs in diagnosing because the central amplification effect produces relatively
pathology. easily identifiable segmental cortical potentials in most pa
tients. I07 •I09 The central amplification effect merely amplifies
Median Nerve the magnitude of the corticaJ response with respect to the periph
Median nerve segmental stimulation can be performed by eral impulse. For example. if a peripheral sensory response
stimulating any of the median nerve's digital branches innervat cannot be recorded, chances are a cortical SEP will continue to
ing the first three digits of the hand. 297 The main differences be be detected because of the so-called central amplification effect.
tween median nerve wrist and digit SEP waveforms are twofold. It is the authors' experience, however, that some normal individ
First, the latency of segmental responses are slightly prolonged uals can have rather small cortical potentials.
compared with mixed nerve stimulation.77.129.264 This latency Erb's Point. This is the same location as that for mixed
prolongation is a result of the distal placement of the stimula median or ulnar nerve studies.77.264 The absence of a response at
tion site plus the small-diameter fibers in the digits conducting this location may simply be due to the small nature of the re
impulses more slowly than the larger caliber wrist fibers. The sponse combined with incomplete patient relaxation and does
second waveform difference is the comparably smaller ampli not necessarily reflect pathology_
tudes for segmental stimulation at all recording sites. Cervical Spine. An identical location as that for mixed
Stimulation. When attempting to generate segmental SEPs, median and ulnar nerve studies is used. Because of the compa
the sensory portion of the peripheral nervous system must be rably smaller segmental SEP spine amplitudes, one may wish to
preferentially activated. As a result, one does not look for a consider the C2S location if spinal recordings are attempted.
muscle twitch. Instead, a stimulus of 2.5-3 times sensory The somewhat larger amplitude at this location may assist in
threshold is applied. IO,111.Z82 Again, a stimulus pulse duration of documenting the desired waveforms more readily than at C5S
200 IlS is preferred with a rate of 5 Hz or less. The current (voltage) or C7S.264.297
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - l89
Scalp. Scalp-recorded potentials are obtained by placing the 0'(093)A + (0.155 + 0.026)AL ± 0.9l.264 Note that these equa
recording electrodes over C3' or C4' just as for the mixed tions utilize ann length and not height. Also, note the C6 spin
median nerve studies. A similar N19 or N20 waveform mor ous process is used rather than C2, C5, or C7.
phology to those for mixed median SEPs is obtained, but the la
tencies are somewhat prolonged as noted above. 297 Ulnar Nerve
Alternate Recordings. The number of channels used can be Ulnar nerve segmental SEPs are comparable in technical
less than for mixed nerve studies. Because of the smaller ampli demand with median nerve segmental studies. Segmental
tude for Erb's point and cervical spine locations, these sites may studies in general, and ulnar sensory SEPs in particular, have
be eliminated. Only 1 channel is then required to record seg been touted for a number of diagnostic uses and are dis
mental SEPs. As there is still 1 channel in a 2-channel instru cussed later. Only techniques are described in this section.
ment, a peripheral nerve recording can be obtained by locating a Once again, meticulous technique is crucial to obtaining
set of recording electrodes over the median nerve just proximal these responses.
to the medial epicondyle over the neurovascular bundle about Stimulation. One convenient way to activate ulnar sensory
the medial aspect of the ann. 77 This enables one to calculate pe fibers properly is to securely place two ring electrodes on the
ripheral nerve conduction velocities. Certainly, if a 4-channel fifth digit, with the cathode proximaJ.297 A pulse width of 200
instrument is available, it is possible, although technically diffi Ils is applied at an intensity approximating 2-3 times the sen
cult, to record not only the cortical potentials but also the pe sory threshold at a rate of 5 Hz or less as previously described
ripheral (ann and Erb's point) as well as spinal potentials. for segmental median nerve studies,77.lo7.111 Again, the gap in
Instrument Parameters. The same instrument settings used the noose portion of the electrode should be positioned posteri
for mixed nerve studies can also be employed for segmental orly. Sufficient electrode paste is placed on the electrodes to
studies. One investigator who has extensively studied segmental provide adequate electrical contact yet not ooze toward its
SEPs prefers a bandwidth of 0.5-200 HzI07 because of introduc neighboring electrode to avoid forming a conductive bridge
ing less high frequency noise yet not distorting the potential across the skin. The ring electrodes are ensured good contact
compared with the 1(}"'3000 Hz and (}"'2000 Hz bandwidths pre by rotating them several times on the finger whereby the skin
viously noted for peripheral and cortical responses, respec impedance is reduced.
tively.17,297 Slightly higher sensitivities and more averages may Ground. Similar concepts apply regarding ground electrode
be required, particularly in less than completely relaxed patients. placement as previously noted for the median nerve.
Reference Data. There is less reference data (Table 9-9) Recording Electrodes. The same electrode sites are utilized
available for segmental studies, as they have not been exten as previously described for both mixed and sensory median
sively documented in either control subjects or patients with nerve studies. An attempt at recording potentials from Erb's
various lesions. Although the technique is somewhat more de point or the cervical region is not always performed because of
manding than for mixed nerve examinations, with a little prac potential amplitude variability.297
tice rewarding recordings can be obtained. Optimal reference Erb's Point, Cervical Spine, Scalp. Identical electrode sites
values would account for various patient ages and heights, but and preparation are used for ulnar nerve sensory SEPs as those
available data often do not. Regression equations accounting for for median nerve sensory SEPs.
age and ann length (metacarpophalangeal joint to C-6 spinous Alternate Recordings. The number of recordings, as
process with ann pronated and abducted 90°) are available. For always, depends upon the number of channels available,
the first digit an equation is: N19;::; 7.17 + (0.0219 ± O.OI09)A + Possibly the most fruitful additional recording site is that of a
(0.168 ± 0.036)AL, where A is age (years) and AL is the pa peripheral nerve. 52•77 This response should be large enough to
tient's arm length (cm) using a standard deviation of + L 1 ms. 2M produce reliable amplitude and latency measuring points. The
The third digit has an equation of N19 ;::; 7.86 + (0.0299 + peripheral potential can serve as a marker for peripheral nerve
function particularly in light of the fact that the other two needle electrodes can also be utilized to produce sufficient
recording sites, Erb's point and cervical spine, are often not ob stimuli at a lower current and may be tolerated better by some
tainable even in normals. patients. 147
Instrument Parameters. Similar instrument settings uti Ground. Similar placement is used as previously recom
lized for the median nerve sensory SEPs also apply for the ulnar mended for median and ulnar nerve studies.
nerve. The most important concept to remember is that what Recording Electrodes. Erb's Point, Cervical Spine, Scalp.
ever reference data base is used, the same filter and amplifier These are the same sites used for the above-noted nerves. Again,
parameters must be used. the small nature of the responses may preclude recording of
Reference Data. If the median nerve cortical sensory SEP waveforms from these sites.
can be obtained, one can expect to detect the ulnar nerve SEP. A Alternate Recordings. If a peripheral nerve response is de
few normal studies utilizing a limited number of patients, espe sired, one can place recording electrodes halfway between the
cially of relatively younger age groups, have been published biceps tendon and the lateral epicondyle along the antecubital
(Table 9-10).77.107.111 crease. 77
Instrument Parameters. See ulnar and median nerve sen
Superficial Sensory Radial Nerve sory SEP recommendations.
SEPs obtained by stimulating the superficial radial nerve at Reference Data. As with all segmental studies, few investi
the wrist yield relatively reliable and reproducible cortical SEP gations have documented normal values for the various SEP
responses.77.107.147 Once proficiency is gained with digital nerve waveforms (Table 9-11). The interested reader is referred to the
excitation. little trouble should be experienced in performing original investigations for discussions regarding the utility of
superficial radial nerve stimulation. these procedures in various pathologic casesJ7.107,329
Stimulation. The superficial radial nerve can be excited at
the wrist about 2 em proximal to the radial styloid.77.147.329 Lateral Antebrachial Cutaneous
Readers are encouraged to develop their own reference data (Musculocutaneous Sensory) Nerve
base for this location. A 200-jls stimulating pulse delivered at 5 SEP evaluation of this nerve has been recommended to assist in
Hz or less at an intensity of 2-3 times sensory threshold results the diagnosis of peripheral nerve injuries to the musculocutaneous
in well-defined superficial radial nerve SEPs. A surface bar nerve or lesions involving the C5 nerve root. 1I1 Obtaining repro
electrode, anode distal, is preferred. However, subcutaneous ducible SEPs of this nerve may take a little practice and patience.
Stimulation. Placing the cathode 2 cm lateral to the biceps sensory evoked potential examinations involve either segmental
brachii tendon and approximately two fingerbreadths distal to or dermatomal excitation. Segmental stimulation is similar to
the antecubital crease optimally excites the lateral antebrachial that noted for upper limb studies where an accessible branch of
cutaneous nerve.77. 107 The anode is positioned distal to the cath a peripheral nerve is excited. Dermatomal studies are performed
ode. As previously noted, a bar electrode, surface disks, or sub by activating the terminal branches of peripheral nerves as they
cutaneous needles may be used. An alternative method of innervate the patch of skin representing the signature area for a
stimulating this nerve is accomplished by locating the cathode particular dermatomal distribution. It is the authors' experience
5.5 cm proximal to the radiocarpal joint, between the tendons of that lower limb dermatomal and segmental studies are some
the flexor carpi radialis and the radial artery.294 The anode is what easier to perform than upper limb segmental SEPs because
placed 2.5 cm distal to the cathode. A 200-l1s pulse duration is lower limb cortical waveforms are usually larger.
delivered at 2-3 times sensory threshold at a rate of 5 Hz or less.
One should avoid stimulating the underlying muscles (as visible Mixed Nerve Somatosensory Evoked Potentials
from a twitch) because this can generate evoked potentials due The tibial and common peroneal nerves are both relatively
to muscle spindle afferent activation that may arise from differ large, subcutaneous, and readily excited by routine peripheral
ent segmental levels than those desired. nerve stimulation techniques at easily demarcated anatomic
Ground. The ground electrode can be placed on the mid sites. The tibial nerve is found just medial to the medial malleo
portion of the biceps brachii or on the sternum as previously lus and proximally in the mid-popliteal fossa, while the
described. common peroneal nerve lies just posterior to the fibular head.
Recording Electrodes. A slight variation in the recording Stimulating electrodes placed at these sites yield large and char
electrodes is necessary to observe the peripheral nerve response acteristic cortical responses. Additionally, only one E-t scalp
(see below). The remainder of the peripheral and central elec recording site is required for left and right stimulation because
trode locations are the same as those for median and ulnar nerve. this electrode is placed just posterior to the cranium's vertex
Erb's Point, Cervical Spine. Scalp. See previous electrode (CZ'), which overlies that region of the volume conductor be
suggestions for the median sensory SEP response. tween the two cerebral hemispheres. The somatosensory cortex
Alternate Recordings. To record the peripheral nerve re representing the lower limb is located on the medial aspect of
sponse of the lateral antebrachial cutaneous nerve successfully, the brain facing the contralateral side (Fig. 9-2). Occasionally
a recording electrode should be placed medially in the deltopec one may wish to use paravertex recordings (CI'/C2') for those
toral groove at the level of the humerus' greater tubercle. 77 An cases when cortical responses are not optimally obtained or
E-2 electrode can be positioned over the ipsilateral acromion. when doubt exists as to the presence of pathology. The spinal
Instrument Parameters. See ulnar and median nerve sen potentials are somewhat more difficult to obtain than the cervi
sory SEP recommendations. cal potential in the upper limb.
Reference Data. Very few investigations have attempted to
document reference data for this nerve (Table 9_12).77.107.294 Tibial Nerve
Practitioners are encouraged to develop their own reference Stimulation. The tibial nerve can be excited at either of two
values. easily located regions, i.e., the ankle or popliteal fossa. 249.309 Both
sites yield relatively large responses, and it is recommended that
LOWER LIMB SEPs the practitioner become familiar with both techniques. Although
neither location holds a distinct advantage over the other, the
Just as for upper limb SEPs, there are several methods for ob practitioner may prefer one of the two techniques or individual
taining lower limb SEPs: mixed nerve techniques and two types patient circumstance may necessitate a specific stimulus site, e.g.,
of sensory SEP studies. The mixed nerve investigations usually a below the knee amputation requires popliteal fossa stimulation.
involve either the tibial or peroneal nerve. The tibial nerve is by Medial Malleolus. The tibial nerve can be easily located
far the most common lower limb nerve examined. Lower limb posterior to the medial malleolus by observing or palpating for
392 - PART II BASIC AND ADVANCED TECHNIQUES
the arterial pulsations in this region. Either surface or needle spinous processes. The lA spinous process is easily identified
electrodes can be used for stimulation. Should an individual by palpating the superior margins of the iliac crests with the fin
have significant adipose tissue overlying the tibial nerve, needle gers and bisecting a line between them with the thumbs palpat
electrodes may be required to deliver an adequate stimulus. In ing the intervening spinous process, Le., L4. The next most
most cases, however, a surface electrode suffices. A bar elec rostral spinous process is L3. An E-l electrode is placed over
trode (inter-electrode separation not critical) is preferred be one of these spinous processes after the skin has been appropri
cause significant pressure can be applied to the electrodes by ately abraded to reduce the impedance to less than 5000 Q. An
placing the tape over the intervening plastic bar and thereby ap E-2 electrode is then secured about 3 cm proximal to the E-J
proach the nerve. Plastic tape with a slight amount of elasticity electrode, which approximates the level of the L2 spinous
is optimal, as it develops a counterpressure when firmly secured process. Alternatively, the E-2 electrode can also be situated on
and stays in place throughout the procedure. An alternate the iliac crest contralateral to the stimulated limb. 244 ,303 The
method of stimulating the tibial nerve is to place the stimulating lumbar potentials are relatively small compared with the corti
cathode 8 cm proximal to a point located 1 cm posterior and 1 cal SEP waveforms. Preferentially increasing the gain on the
cm inferior to the navicular tubercle on the medial side of the third channel may aid in recording the lumbar potentials. It is
foot 77 This may be a bit too proximal in some patients to excite crucial for the patient to be completely relaxed, especially with
the nerve adequately because of subcutaneous tissue. Similar respect to the paraspinal muscles, to detect the lumbar potential.
stimulation parameters as those described for the median nerve Some authors recommended giving the patient medication to
can be used.52.282 A stimulus rate of between 2 and 3 Hz rather maximize relaxation.242.272.273 If sedation is administered, it is
than 5 Hz is preferred to record lower limb SEPs optimally. The incumbent upon the physician to ensure that the patient is ade
goal of the stimulating pulse is to induce a moderately vigorous quately warned regarding operating motor vehicles or perform
twitch of the great toe or abductor hallucis muscle. Should the ing any other task requiring one to be fully alert. Although
patient complain of excess stimulus discomfort, the skin should investigators report the lumbar potential being present in all
be mildly abraded to reduce the impedance and, therefore, the normal individuals, this has not been the authors' personal expe
amount of current required. If discomfort continues, the current rience, particularly in elderly subjects. 175.201,239,244 Thus, the ab
simply may be too intense for the depth of the nerve and slight sence of a potential is not diagnostic of pathology.
repositioning of the stimulus site should be tried or the use of Thoracic Spine (Ti2, Ll). Following placement of the
stimulating needle electrodes employed. lumbar electrodes, the next set of electrodes are located over the
Popliteal Fossa. The tibial nerve is excited at the popliteal thoracic spinous processes and connected to the second chan
fossa by asking the patient to first flex the leg slightly. This nel. The TI2 spinous process is found by locating the L4 spine
allows the tendons of the semitendinosus and semimembra and placing the E-l recording electrode on the fourth spinous
nosus medially and the biceps femoris laterally to become process cephalad. This TI2S electrode serves as the central con
prominent. Half-way between these tendons and 2 cm proximal duction marker for the most caudal portion of the spinal cord.
to the popliteal crease is the recommended location for the cath An E·2 electrode is usually positioned about 3 cm rostral to TI2
ode.?7 The anode is located several centimeters distal to this site. or over the TIO spinous process. The same remarks regarding
Similar stimulation parameters as those noted for the ankle are skin preparation and ease of recording for the lumbar potential
used, but more current may be required. apply to the thoracic potential. An iliac crest E-2 electrode may
Ground. As with previously delineated SEP techniques, the help record particularly small spine potentials because of the
ground should be placed between the stimulating and first set of referential nature of the recording (see above). Some authors
recording electrodes, preferably closer to the recording elec prefer the L1 as opposed to TI2 spinous process. In either case,
trodes. When recording from the lumbosacral region (see essentially the same potentials and latencies are recorded.
below), the ground can be conveniently located on the low back Scalp. An E-1 electrode is located at CZ', while the E-2 elec
region in the midline, which suffices for both left and right sided trode is placed at FpZ' for the first channel recording. This
excitations. recording montage serves both left and right tibial nerve stimu
Recording Electrodes. A 4-channel technique is recom lation, as do the spinous process electrode sites.
mended for recording lower limb SEP studies. 6•7 In order to Alternate Recordings. When the tibial nerve is stimulated
obtain the maximum amount of data from a lower limb SEP at the popliteal fossa, it is obviously impossible to record from
evaluation, one must use four recording sites. However, one this same location simultaneously. In this instance, the fourth
should not conclude that practitioners with 2-channel instru channel records a response from the sciatic notch. 77 An E-l
ments are precluded from doing acceptable lower limb SEP electrode is positioned over the sciatic notch (as described
studies (see below). below for the peroneal nerve), while the E-2 electrode may be
Popliteal Fossa (PF). When stimulating the tibial nerve located over the greater trochanter. Reducing the impedance is
about the ankle region, the first recommended recording site is crucial for successful recordings because of the amount of
the popliteal fossa. 6•7 .77 ,201.281 The potential obtained from this p0 tissue overlying the sciatic notch. Like the thoracolumbar po
sition is the propagating mixed nerve action potential initiated tentials, the sciatic notch potential may not be present in all in
posterior to the medial malleolus. The popliteal fossa potential dividuals. The use of a needle recording electrode is not
serves as the marker for peripheral nerve function. An E-l recommended. When studying the tibial nerve, some investiga
recording electrode is positioned exactly as that noted for the tors have utilized a C7-FpZ' recording montage to delineate the
stimulating cathode at the popliteal fossa as described above.?7 spinal cord voHey in the cervical region in order to calculate the
The E-2 electrode is located on the medial joint line of the knee. spinal cord conduction time. 269--271 Of note, the cervical potential
This is the electrode montage usually recorded on channel 4. is extremely small in some individuals and bilateral tibial nerve
Lumbar Spinous Process (13, LA). The third channel is used stimulation may be required to observe this potential.
to record the nerve volley traveling in the cauda equina as Instrument Parameters. As the distance for the neural
recorded by an electrode placed over the L3 (L3S) or lA (L4S) volley is greater for lower compared with upper limb studies, an
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 393
analysis time of 100 ms (sweep 10 ms/div) is required. Because Figs. 9-12,9-13, and 9-14). As previously noted, it is a good
cortical potentials are relatively large, a sensitivity of 2.0 IlV/div practice to develop one's own reference data base.
usually suffices, although one should be prepared to increase
the sensitivity. Lumbar potentials may require a final signal am Peroneal Nerve
plification of 1.0 IlV/div or possibly 0.5IlV/div. About 500 aver SEPs of the peroneal nerve can be performed as easily as
ages result in distinct cortical potentials, but 1000 or more tibial SEPs, although cortical responses are often smaller, The
averages may be necessary to resolve the spine potentials, espe authors know no advantage regarding neural information in per
cially in less than completely relaxed patients. The usually rec forming peroneal compared with tibial SEPs unless there is a
ommended filter settings of 10 Hz and 3000 Hz produce specific clinical indication to examine the peroneal nerve, e.g.,
adequate responses, although they can be a bit noisy. absent tibial nerve, lesion affecting the peroneal nerve, or a re
Decreasing the high-frequency filter to 1000 Hz will reduce the search protocol. There is comparably less SEP data available for
noise without significantly affecting the responses' latency or the peroneal than tibial nerve,20,65,255,304,307,329
amplitude. Stimulation. The peroneal nerve can be easily identified in
Reference Data. The tibial nerve has been extensively in its location posterior to the fibular head about the knee. 77 •154 A
vestigated with respect to both reference data and alterations in cathode is positioned just inferior to the fibular head, while the
pathologic states.9,11.I2.52,77 The large amplitudes and ease of de anode is placed several centimeters distal to the cathode. The
tection are major reasons this nerve has been explored in such same stimulus parameters as used for the tibial nerve are uti
detail. The beginning practitioner is strongly urged to consider lized, One should note the clinical manifestation of peroneal
beginning one's SEP experience with the tibial nerve. The refer nerve activation, i.e., primarily ankle dorsiflexion and eversion,
ence data presented are compiled from several sources and Ground. The ground electrode is again located near the first
demonstrate the consistency of the tibial response (Tables 9-13 set of electrodes at the sciatic notch, but one may wish to place
and 9-14). Regression equations considering height (cm) and the ground electrode on the back, which obviates the need of
age (years) have been formulated to assist in the development of repositioning this electrode.
reference parameters in large populations,53 In men, the spinal Recording Electrodes. The first E-J recording electrode is
potential L1 latency (N22) is found to have an ~uation of N22 slightly different than that for the tibial nerve, as stimulation is
= 0.174(H) + 0.076A - 9.2525, while P37 (40) = 0.199H + now in the popliteal fossa. A slightly more proximal site is sug
0,0852A + 3.8025, where H and A equate to height and age, re gested for peroneal nerve studies. Although 4 channels are rec
spectively. The same respective equations in women are: N22 = ommended,6.7,77 it is the authors' opinion that adequate studies
0.1619H + 0,0694A 7.5235 and P37 (40) =
0.2222H + can be carried out using 2 channels. The most important data to
0.5995A + 1.1210. Equations for the central conduction times be collected are the spinal arrival time (TI2) and cortical arrival
for men and women are N221P37 =0.944H + 0.0233A 0.2730 (P37IN45).329 If more data are required, the sciatic notch and
and N22/P37 = 0.0943H + 0.0425A 0.2076, respectively.53 lumbar potentials can be collected with a second set of stimuli,
Slight differences are believed to occur secondary to gender by inconvenient though this may be.
the investigators reporting the above regression equations. Not Sciatic Notch. Because the popliteal fossa is not available for
all authors agree with these findings (see above). Graphic plots recording. the next anatomic site of possible interest is the sci
can also be used from which the equations can be derived (see atic notch, which is recorded on channel 4.77 The E-l electrode
194 - PART II BASIC AND ADVANCED TECHNIQUES
site is located by palpating the greater trochanter and ischial morphology, latency, and amplitude as well as their anatomic
tuberosity. An imaginary line is drawn between these two areas significance. An E-2 electrode is located 3 em proximal to the
and bisected. This region should place the E-l electrode in the E-I electrode or placed on the iliac crest contralateral to the side
vicinity of the sciatic nerve as it is about to enter the pelvis. The of excitation.
greater trochanter serves as the E-2 electrode site for the sciatic Thoracic Spine (TI2). A third set of electrodes records the
notch. action potential volley traversing the spinal cord's caudal seg
Lumbar Spinous Process (L3, lA). On the third of the 4 ment from the region of TI2. The E-2 electrode again is placed
channels, the L3S or L4S spinal potential is recorded. Some in 3 cm proximal to the spinous process of the twelfth thoracic
vestigators prefer L3, while others record from the L4 spinous vertebra (about TIO) or on the iliac crest. When using the iliac
process. The potentials are essentially the same in terms of crest, one should be prepared for a relatively more noisy trace,
as there is less common mode signal between these 2 electrodes particularly as it travels posterior to the lateral malleolus. S-l
compared with the situation when both electrodes are close to nerve root fibers constitute the primary but not exclusive root
each other on the thoracic spines. level contributing to the sural nerve. 107,111.154,184
Scalp. The same locations used for tibial nerve SEPs elec Stimulation. The sural nerve can be rather easily excited by
trodes, CZ' and FpZ', are utilized for peroneal nerve cortical placing a cathode in the depression between the lateral malleo
recordings. lus and the Achilles tendon. The nerve lies in this anatomic
Alternate Recordings. As noted above, if only the cortical region and generates relatively large cortical SEPs. An anode
and Tl2 spine potentials can be recorded, sufficient data have should be placed several centimeters distal to the cathode. The
been obtained for most routine purposes. An inability to obtain a fact that the sural nerve is purely sensory requires that stimula
sciatic notch potential or lA potential does not necessarily imply tion be effected in a particular manner quite distinct from that
that an inadequate study has been performed or that the patient is used for the mixed tibial and peroneal nerves, Le., determining
abnormal. The peripheral nervous system can certainly be exam the sensory threshold and exceeding it by 2.5-3.0 times.
ined with peripheral nerve conduction techniques. Ground. The ground electrode can be located just distal to
Instrument Parameters. See tibial nerve recommendations. the popliteal fossa or on the sternum. Good skin preparation
Reference Data. As previously noted, there is not an abun should be performed at the chosen site.
dance of normal values for peroneal nerve studies (Table 9 Recording Electrodes. The recording of segmental SEPs is
15).77,329 Although this is not a technically difficult study to somewhat different than mixed nerve studies with respect to
perform, it is a good idea to practice this study on normal sub the number of channels and recording sites. The extremely
jects prior to investigating potential abnormalities of the per small amplitude of segmental spinal potentials precludes their
oneal nerve. routine detection. As a result, only I channel is routinely uti
lized by the authors to observe the cortical potential. Oc
LOWER LIMB SEGMENTAL SOMATOSENSORY casionally, a popliteal fossa recording is attempted to assess
EVOKED POTENTIALS peripheral nerve function. It is also possible to record spinal
potentials in patients capable of maintaining adequate
As previously defined, segmental SEP studies examine the paraspinal muscle relaxation.239.24o
peripheral activation of a pure sensory nerve such as the superfi Popliteal Fossa (PF). The E-I and E-2 electrode sites rec
cial radial nerve. In the lower limb, a number of segmental SEPs ommended for the sural nerve are the same as those for the
can be easily performed by the beginning practitioner. These tibial nerve. 77 Although good skin preparation is required for
studies have primarily been utilized to evaluate lumbosacral any SEP, segmental studies are particularly demanding, as the
radiculopathies. 107,111,240 The sensitivity and specificity of seg pure sensory nature of responses can at times result in a rela
mental studies with respect to lumbosacral radiculopathies tively small potential.
remain controversial. This controversy is not presently explored Scalp. Sural segmental SEPs utilize the same cortical recording
but will be discussed in the chapter considering radiculopathies. positions used for tibial nerve SEPs, Le., CZ' and FpZ'. Again, the
At this time, only the technical aspects of eliciting segmental same recording electrodes are employed for both left and right
studies and reference data are presented. limbs. The morphology of segmental cortical responses is similar
to mixed nerve SEPs, Le., there is usually an initial large positive
Sural Nerve deflection followed by a large negative deflection. If the peripheral
The sural nerve is a relatively large sensory nerve comprised nerve potential is also recorded, channel 2 is used to document this
of fibers originating from branches of both the tibial and peroneal response; otherwise, channel 1 is used. Thus, a 2-channel instru
nerves. 154,286 Anatomically, the sural nerve is rather superficial, ment is quite adequate for segmental SEP studies.
Alternate Recordings. The small amplitude of the segmen Scalp. The montage previously noted for the sural nerve, CZ'
tal response usually precludes spinal recordings. and FpZ', is also used for this nerve. The morphology of the cor
Instrument Parameters. A sweep of 10 ms/div and sensi tical response is similar to that noted for other lower limb SEP
tivity of 1-2lN/div with filter settings of 10-3000 Hz are typi responses.
cal for sural nerve segmental studies, which are the same as Alternate Recordings. Because of the small nature of the
those used for the tibial nerve. Averaging approximately 500 re spinal potentials, attempts to record from the lumbar or tho~ic
sponses typically yields good waveforms. spine are quite challenging and preclude routine observation of
Reference Data. Because of the ease of performing the sural these responses. A 2-channel instrument, therefore, is quite suf
SEP, a number of investigators have provided data for this nerve ficient for the superficial sensory peroneal nerve.
(Table 9_16).52.77.240 Instrument Parameters. The same instrument parameters
noted for the sural nerve suffice. As always, two trials of each
Superficial Sensory Peroneal Nerve response should be performed to ensure reproducibility.
The superficial sensory peroneal nerve is the cutaneous branch of Reference Data. Compared with the sural nerve, fewer stud
the superficial peroneal nerve. 154. 167,286 Approximately 12 cm proxi ies have been performed on the superficial sensory peroneal
mal to the ankle, the superficial sensory peroneal nerve pierces the nerve (Table 9_17).17.107,240 Although the technique is relatively
superficial fascia to become a cutaneous nerve. 169 This nerve pro easy, the clinical utility of SEPs from this nerve is questionable
ceeds distally to form the medial and intermediate dorsal cutaneous and hence the lack of various reference data bases.
nerves, which pass anterior to the extensor retinaculum to innervate
the foot's dorsal aspect. The cutaneous fibers of this nerve are be Saphenous Nerve
lieved to consist primarily of fibers from the L5 nerve root. It is, The saphenous nerve is the cutaneous termination of the
therefore, possible to perform an SEP from the superficial sensory femoral nerve. This nerve enters the femoral triangle along with
peroneal nerve and investigate the sensory portion of the L5 root the femoral artery and passes through Hunter's canaL 154 Distal
Stimulation. The superficial sensory peroneal nerve can be to this region, the saphenous nerve provides a cutaneous branch
anatomically located by drawing an imaginary line connecting to the medial portion of the knee known as the infrapatellar
the medial and lateral malleoli. A cathode is located at the junc branch of the saphenous nerve. 154.254 The main saphenous trunk
ture between the middle and lateral thirds of this imaginary continues distally into the leg in the groove formed by the
line.77.168 The anode is located several centimeters distally. medial aspect of the tibia and the bulk of the medial gastrocne
Electrodes imbedded in a plastic bar are convenient to use as the mius muscle. Branches of the nerve terminate on the medial
cathode and anode. The same parameters described above for aspect of the foot by passing anterior to the medial malleolus.
the sural nerve are utilized for the superficial sensory peroneal The cutaneous distribution of the descending saphenous nerve
nerve. It is also possible to stimulate the superficial peroneal is the medial aspect of the leg, ankle, and foot, sometimes
nerve 12 cm proximal to the lateral malleolus.I07.11I.24O reaching the great toe. The saphenous nerve can be excited
Ground. The ground can be on the patella or more proximally. along its course at the infrapatellar region, medial aspect of the
Recording Electrodes. The same principles described for leg, or the ankle.
the sural nerve also apply to the superficial sensory peroneal Stimulation. One may wish to excite different portions of
nerve. Only 1 channel is used to perform this study, although a the saphenous nerve along its course depending upon the possi
logical argument can be made for a 2-channel recording. ble lesion site.97 •296 The most distal aspect of the saphenous
Popliteal Fossa (PF). Channell may record potentials at the nerve can be stimulated at the ankle as it accompanies the
popliteal fossa, as the neural impulses traverse this region. To saphenous vein. 107.1II A bar electrode is convenient, but separate
detect this potential properly, it is necessary to use a rather high surface electrodes are equally effective. The patient is requested
sensitivity (1.0 j.lV/div) because of the response's small ampli to gently dorsiflex the ankle on the side of stimulation, and the
tude. Alternatively, the peripheral nerve can be examined with tendon of the tibialis anterior is palpated. If the patient is inca
routine nerve conduction techniques. pable of dorsiflexing the foot, this same site can be located
approximately one fingerbreadth anterior to the medial malleo Knee. When stimulating the saphenous nerve at either the
lus. The cathode is located at this site, i.e., just medial to the tib ankle or mid-leg level, the investigator can attempt to record
ialis anterior tendon in the soft tissue hollow formed between from the peripheral portion of the saphenous nerve as it crosses
the tibialis anterior tendon and the medial malleolus. An anode the knee joint. In this instance, an E-I electrode is positioned
is located a few centimeters distal to the cathode. medially between the tendons of the sartorius and gracilis mus
A second site of stimulation is in the groove formed by the cles 1 cm superior to the inferior border of the patella. 17 A con
medial aspect of the tibia and the medial gastrocnemius. 11•311 venient location for the E-2 electrode is the anterior aspect of
The cathode is located approximately midway between the the patella. This recording montage is connected to channel 2.
medial malleolus and medial tibial plateau. The anode is again This potential may be difficult to detect despite a successful cor
placed several centimeters distal to this site. Another author rec tical potential.
ommends that the cathode be positioned 15 cm distal to a point Scalp. The scalp location for the recording electrodes is the
between the sartorius and gracilis tendons where these muscles same as those used for the sural nerve, i.e., CZ' and FpZ'.
are 1 cm proximal to the inferior border of the patella. 71 Cortical potential morphology is similar to the sural nerve in
The infrapatellar branch of the saphenous nerve can be stud that an initial positive deflection followed by a negative deflec
ied by locating a cathode in the soft tissue depression formed by tion is typical.
the inferior border of the medial aspect of the patella and the su Alternate Recordings. The small amplitude of peripheral
peromedial aspect of the medial tibial plateau.97 ,296 The anode is and spinal potentials obviates their routine detection.
again positioned several centimeters distal to this site. Essentially, the potential typically recorded for the saphenous
The same stimulus parameters for the sural nerve are also uti nerve is the cortical potential.
lized for all portions of the saphenous nerve excited. A sensory Instrument Parameters. Saphenous nerve SEP studies re
threshold is first determined, and then a current intensity ap quire similar instrument parameters as those utilized for the
proximating 2-3 times this sensory threshold is delivered. A sural nerve. In some patients, 500 or more responses may need
small muscle twitch of the medial gastrocnemius may occasion to be averaged in order to obtain clearly recognizable responses.
ally be observed when attempting to activate the saphenous The filter setting used by individual authors may vary somewhat
nerve at mid-leg level. This is most likely direct muscle stimula and should be consulted when reproducing a technique for par
tion not involving a significant number of IA afferents and, ticular patients.
therefore, should not alter the results. Of course, should this Reference Data. There are only a limited number of normal
muscle activation be painful, the electrode should be reposi values available for the saphenous nerve at each of the three
tioned either more proximal/distal or mediaillateral until the stimulation sites (Table 9_18),71,107,240,296 Again. it is highly rec
discomfort is minimized. ommended that the individual practitioner develop laboratory
Ground. The ground electrode can be located on the ipsilat specific normal values.
eral patella or preferably closer to the recording electrodes. As
peripheral recording sites are not very successful in picking up a Lateral Femoral Cutaneous Nerve
response, the ground can often be placed on the sternum or some A direct continuation of the lumbar plexus, the lateral
other convenient location without distorting the cortical SEP. femoral cutaneous nerve consists of sensory fibers from L2 and
Recording Electrodes. There is little opportunity to per L3 nerve roots. 154.254 The nerve courses along the rim of the
form successful peripheral recordings when stimulating the pelvis to emerge through a tunnel formed by the anterior supe
saphenous nerve because of the small nature of this response. rior iliac spine and the lateral portion of the inguinal ligament.
When exciting the saphenous nerve at the knee region, the pe The nerve then descends subcutaneously along the thigh to
ripheral and spinal volley is simply too small to record over the divide, approximately 12 cm distal to the anterior superior iliac
thoracolumbar region. spine, into two branches. One branch provides cutaneous sensation
to the anterior aspect of the thigh, while the second is distrib nerve recording at the ASIS is desired, increasing the sensitivity
uted over the lateral portion of the thigh as far distal as the patel to 0.5-1.0 flV Idiv may be desirable, provided the noise level is
lar region. sufficiently controlled.
Stimulation. The lateral femoral cutaneous nerve can be ex Reference Data. Only a few authors have investigated the
cited by locating a cathode 12 em distal to the anterior superior lateral femoral cutaneous nerve and provided normal values
iliac spine and placing the anode several centimeters distal to (Table 9-19).77.107 As with the saphenous nerve, it is especially
the cathode. 77 •107 Sural nerve stimulation parameters are again important for practitioners to develop their own reference values
used to activate the lateral femoral cutaneous nerve. to ensure proper recording techniques because of the technical
Ground. In the event of using a peripheral recording loca difficulty in recording this SEP.
tion (see below), the ground should be placed just distal to this
site between the stimulating and recording electrodes. If only a DERMATOMAL SOMATOSENSORY
cortical recording montage is used, the ground can be situated EVOKED POTENTIALS
on the sternum or other convenient location.
Recording Electrodes. In the authors' opinion, the lateral SEPs obtained as a result of dermatomal compared with seg
femoral cutaneous nerve SEP waveform is somewhat more diffi mental stimulation are morphologically similar, but the two stim
cult to detect than that of all of the previously noted nerves. The ulation techniques are different. 102 When attempting to record a
reason for this is the small nature of the response at both the pe dermatomal SEP, the stimulus is applied to a region of skin that
ripheral and cortical recording locations. Complete relaxation of represents the autonomous zone of a particular nerve root. The
the patient is particularly important, as any muscle artifact will number of nerve fibers, cutaneous afferents, directly under the
impede detection of the waveform. Meticulous technique is re cathode is considerably less than when a pure sensory nerve
quired at the stimulating and recording sites with respect to ac branch believed to be composed of fibers primarily from one
curate placement of electrodes and skin preparation. nerve root is activated. The clinical utility of both segmental and
Anterior Superior Iliac Spine (ASIS). Should one wish to dermatomal studies is unclear, and the relative value of either
pursue a peripheral recording during the SEP examination, an compared with the other is also unknown. In this section, no at
E-l recording electrode can be located over the emergence of tempt is made to critically analyze the diagnostic importance of
the lateral femoral cutaneous nerve from the inguinal tunnel. 77 either technique; only the methodology of obtaining reproducible
This electrode is positioned about 1 em medial to the ASIS, results is delineated. For an appraisal of the current thinking re
while the E-2 electrode is placed over the ipsilateral greater garding the diagnostic applicability of dermatomal studies, con
trochanter. Adequate skin preparation is mandatory to observe sult the section of this text discussing radiculopathies.
this potential. Do not be surprised if this response is not ob Although a number of studies have been published expound
tained, even on the asymptomatic side. ing the merits of dermatomal SEPs with respect to correctly di
Scalp. CZ' and FpZ' are again used. Particular attention agnosing pathology,IO·184,185,252 minimal work has been done on
must be directed at getting patients to relax cervical and mas attempting to acquire reference data and develop criteria to es
seter muscles to minimize muscle artifact contaminating this tablish normality. The techniques to record dermatomal SEPs
small waveform. The first channel can be utilized for the corti are relatively straightforward. While there are some data on
cal potentials. normal values of various dermatomal SEPs, multiple reference·
Alternate Recordings. Very small lateral femoral cutaneous data bases, particularly regarding the reproducibility and normal
nerve responses preclude spinal recordings. A scalp montage of variance of the dermatomal SEPs, are noticeably absent.
C3/C4-0Z is preferred by some.295 An initial negative deflection Considerable latency (up to 8-9 ms) and amplitude (80%) side
is the first cortical response in this instance. to-side differences can occur in normal persons. IOl •I02
Instrument Parameters. The same instrumentation settings
used for the sural nerve are replicated for this nerve. The only L5 Dermatomal SEP
change required may be an increase in the number averaged to The LS dermatome's signature area is believed to be located
resolve the response, i.e., 1000. Additionally, if a peripheral about the medial aspect of the first metatarsophalangeal joint in
ASIS
(A) 2.9 ± 0.5 0.31-0.75 (8)- (C)
CZ' (P37)
30.2 ± 2.4 0.41-2.89 29.8 ± 1.6 1.5 31.8 ± 1.8
CZ' (N45)
42.5 ± 4.5 0.61-6.72
Interpeak Latency
ASI5-P37 25.2 ± 2.8
Amplitude (IN)
ASIS 0.42 ± 0.21 0.08-0.41
P37 0.32 ± 0.12 0.09-0.28
P37-N45 0.41 ± 0.19 0.15-0.41
Bandwidths for above tech~ques are:A) 10-3000 Hz ~rip~ral and 0-2000 Hz cortical responses, B) not provided, C) 0.5-200 Hz. Magnitude of cortical potentials
are baseline to peak for P37 and peak-to-peak for P37-N45. UR signifies the left/right difference.ASIS: anterior superior iliac spine. In B, a cortical montage of
C3/C4-0Z is used. As a result, an initial negative potential is detected at approximately N29. From DeUsa et al!7 (A), Synek295 (8) and Eisen,07 (C).
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 399
the foot. 125.154 A more exclusive L5 dermatomal region is be at the fifth metatarsophalangeal joint. 125.154 This portion of the
lieved to be on the dorsum of the foot between the first and foot is supplied by the sural nerve, which is thought to consist
second digit by some investigators. JO In any event, the region exclusively of fibers originating from the Sl nerve root. Aside
most likely to represent L5 is on the dorsum of the foot sur from developing a dermatomal SEP technique, there is little dis
rounding the first metatarsophalangeal joint. cussion regarding the clinical utility of S 1 dermatomal stimula
Stimulation. The stimulus parameters are similar to those tion compared with sural nerve segmental stimulation.
for segmental studies in that a pulse duration of 200 /lS is deliv Stimulation. Identical stimulus parameters are used for the
ered at a rate less than 5 Hz at between 2 and 3 times the sen S 1 dermatomal SEP as were utilized for the LS dermatomal
sory threshold. In one study, the mean sensory threshold in SEP. A cathode is placed at the level of the fifth metatarsopha
normal individuals was noted to be 4.1 ± 1.1 rnA for the L5 der langeal joint on the lateral aspect of the foot. An anode is lo
matome with a final stimulus delivery of 9.2 ± 2.6 mA.I84.lss The cated about 3 cm distal to this location. A convenient set of
cathode should be located at either the level of the first metatar stimulating electrodes is the bar electrode. Mildly abrading the
sophalangeal joint along its medial aspectl84.185.245 or in the web lateral margin of the foot beneath the electrodes helps to reduce
space between the first and second digit in the foot. to An anode skin impedance secondary to callus formation. A stimulus of
is located about 2 or 3 cm distal to the placement of the cathode. 2-3 times sensory threshold (4.2 ± l.l rnA) is used, and this has
Mild abrasion of the skin beneath the stimulating electrodes been found to be about 9.2 ± 2.6 rnA.IM
may be necessary in some individuals, as the foot can be heav Ground. The same location and parameters as those for the
ily calloused. L5 dermatome are used.
Ground. The ground electrode can be located on the ster Recording Electrodes. As with the L5 dermatomal re
num, cranium, or some other convenient location such as the ip sponses, the small number of fibers excited precludes reliable
silateral patella. It is a good idea to mildly abrade the skin under peripheral or spinal recordings. The absence of peripheral
the ground site to ensure good contact to reduce interference recording sites, however, is somewhat of a limitation in that an
and artifact because the dermatomal responses can be rather abnormal cortical response may result from abnormalities any
small, particularly in various pathologic conditions. where along the nervous system from just proximal to the site
Recording Electrodes. Stimulating a dermatome involves a of stimulation to the somatosensory cortex itself. This is one ob
small number of cutaneous afferents. This fact most likely pre vious limitation of the dermatomal response.
cludes recording reproducible peripheral or spinal responses. As Scalp. Because the somatosensory cortical representation of
a result, all investigations to date have utilized only cortical the entire foot is in the same general area, there is no difference
recording electrodes. As with other SEPs, the scalp electrodes in location for the S 1 scalp recording electrode compared with
can be either surlace or subdermal needle electrodes. the L5 electrode. As a result, the E-l electrode is placed at CZ'
Scalp. The scalp recording electrodes are positioned in the while the E-2 electrode is at FpZ'. This location should result in
same location as that used for all lower limb SEP studies. An E clearly identifiable waveforms that are similar in appearance to
1 electrode is placed at CZ', while an E-2 electrode is located at those obtained for tibial nerve stimulation.
FpZ'. This cortical montage should result in well-defined L5 Alternate Recordings. The same as those for the L5 der
dermatomal responses. Because only the cortical potentials are matomal SEP.
recorded, a single channel is all that is required. Instrument Parameters. Same as the L5 dermatomal SEP.
Alternate Recordings. There are no additional responses nor The details in the original studies need to be reviewed to fully
mally recorded for dermatomal responses. However, should more appreciate the nuances in successfully obtaining responses that
channels be available, various cortical montages can be used to conform to the waveforms as initially reported.
help identify the vertex responses, e.g., CI' or C2' referenced to Reference Data. With respect to reference data, the same
FZ or CZ' referenced to the contralateral C3'/C4' locations. 10 comments apply to S 1 dermatomal responses as those already
Instrument Parameters. An analysis time of 100 ms noted above for L5 waveforms (Table 9_21).10.184.244 The regres
(sweep of 10 ms/div) combined with 500 to 1000 averages sion equation for the SI dermatome relating age (years) and
should be sufficient to resolve most LS dermatomal responses. height (meters) is: P(40) =8.6 + 24.0 (Height) + 0.038 (Age) ±
Amplifier sensitivity of 1 or 2 11VIdiv is adequate. Two studies 2.9 ms.IM The same general rules of prolonged peak latency for
have presented reference data each using different filter settings.
One of the investigations examined the responses at various
bandwidths and concluded that there was no statistically signifi Table '·20. LS Dermatomal SEP Reference Data
cant difference in waveform parameters between filter setting of latency(ms)
5-250 Hz and 1-1S00 HZ.IM.ISS A second study utilized
30-3,000 Hz.IO As always, until more data are available, it is a To Peak UR To Peak UR
good idea to reproduce exactly the conditions under which par Recording Site
ticular data are obtained if these data are to be utilized. ez' (P37) (A)48,4 ± 3.9 -0.6 ± 1.7 (8)51.0 -(J.5S ± 2.1
Reference Data. Very few studies have systematically and ez' (N4S) 58.8 ± 4.3
clearly attempted to formulate a complete data base (Table 9
Amplitude (IJV)
20).10.184.245 Dermatomallatencies are directly correlated to age
Max Ratio
(years) and height (meters) just as are other SEPs. A regression
equation for the LS dermatomal P37(or P40) latency responses
ez' (P37) 0.09-2.36 4:1 0.6±0.4 -
is given as: P40 8.3 + 22.4 (Height) + 0.086 (Age) ± 2.7 ms.IM
ez' (P37-N4S) 0.28-4.17
L5 was stimulated at the medial aspect of the first digit for A while the first web
51 Dermatomal 5EP space was utilized for B. Magnitude of cortical potentials are baseline-to-peak
for P37 and peak-to-peak for Pl?~. Filter setting for techniques above are:
An exclusive region of dermal cutaneous innervation by the A & C) 5-250 Hz. and B) 30-3000 Hz. UR signifies the left/right difference.
S 1 nerve root is thought to occur at the lateral margin of the foot From Katifi et al.'84 (A).Aminoff et al.'· (B).
400 - PART II BASIC AND ADVANCED TECHNIQUES
Table 9-21. S I Dermatomal SEP Reference Data to between 2 and 3 times the sensory threshold delivered at less
Latency(ms) than 5 Hz is optima1.148.149 An alternate technique is to place a
bar electrode on either side of the penis consecutively to com
To Peak UR To Peak UR
pare left and right responses.
Recording Site In the female, the same stimulation parameters are employed
CZ' (P37) (A) 49.9 ± 3.9 -0.15 ± 2.3 (8) 52.3 -1.17 ± 1.7 but obviously the electrode locations must differ. Typically a.bar
CZ' (N45) 60.2 ± 4.4 electrode is placed on the labia majora for left-right comparison
Amplitude bN) studies. 15I In the authors' experience, the pudendal SEP tech
Max Ratio nique is somewhat more demanding in the female than in the
CZ' (P37) 0.26-2.84 3:1 0.5 ± 0.4 - male patient. In normal females, it is often difficult to record
CZ' (P37-N45) 0.30-5.85 either the left or right response. The main reason for this diffi
Filter settings for the above techniques are:A) 5-250 Hz and B) 30-3000 Hz.
culty may be cutaneous moisture that short-circuits the current
Magnitude of cortical potentials are baseline-to-peak for P37 and peak-to-peak across the skin's surface as opposed to activating the cutaneous
for P37-N45. LlR signifies the left/right difference. From Katifi et al.'" (A), skin afferents, i.e., in the female, it is a dermatomal response
Aminoff et al.'o (B). but segmental stimulation in the male. Proper drying of the labia
is critical to obtaining pudendal SEPs. In both the male and
an increase in age and height apply to the S 1 dermatome SEP as female patient, stimulation is only mildly uncomfortable and
they do for all other SEPs. patients often require reassurance because of the stimulator's
location. A chaperone is appropriate when performing this pro
cedure in patients of the opposite sex to the practitioner.
MISCELLANEOUS SEP TECHNIQUES Ground. A mid-sternal or abdominal ground electrode can
be utilized, and either location works equally well.
Although an SEP can be performed for just about any acces Recording Electrodes. The cortical SEPs are easily ob
sible nerve, only a few nerves have been examined with respect tained and are of sufficient amplitude to be readily recognized.
to reference data. The clinical utility of these procedures is dis The investigator '48,'49 who popularized this technique even per
cussed in detail when appropriate in other sections of this text forms spinal recordings, although it is the authors' experience
relating to specific lesions involving the nervous system. The that spinal potentials can often be difficult to document.
technique, instrumentation parameters, and reference values are Scalp. The pudendal SEP is best recorded with an E-! elec
presently described so as to allow the successful recording of trode located at CZ' referenced to FpZ'. As for all other scalp
these waveforms. SEP recordings, subdermal needle recording electrodes are pre
ferred, but surface electrodes provide equally successful re
PUDENDAL NERVE SEP sponses with proper skin preparation.
Spine (Ll). An Ll electrode can occasionally record a re
The pudendal nerve is a continuation of the sacral plexus and sponse in some men,148 but this response is rarely observed in
is formed by nerve roots S2-4. 136,154.286 The cutaneous afferent women. lSI The reason for this difference is most likely that seg
component of the pudendal nerve of interest to SEP investiga mental responses are obtained in men and hence more nerve
tions is the dorsal nerve of the penis in males and dorsal nerve fibers are activated compared with dermatomal (less nerve
of the clitoris in females. Pudendal SEPs are of interest because fiber) stimulation in women. When spinal potentials are at
they investigate the afferent component of the lower sacral tempted, they may be recorded on channel 2.
nerve roots, which are difficult to examine by other electrodiag Alternate Recordings. No other recording/stimulating
nostic techniques. Although the anal sphincter (motor compo montages have been reported.
nent S2-4) muscle can be explored with a needle electrode,314 Instrument Parameters. Because of the segmental or der
continuous tonus of this muscle often renders the study of activ matomal nature of these responses, similar instrument settings
ity at rest less than optimal. The clinical utility of pudendal as those used for dermatomal studies are recommended, specifi
SEPs is in the area of sexual dysfunction and compromise of the cally an analysis time of 100 ms (sweep of 10 ms/div) with a
lower sacral nerve roots. 136,148.149.150.151 sensitivity of ! or 2lJV/div and filter settings of 0--2000 Hz76 or
Stimulation. In males, the cutaneous portion of the puden 5-250 Hz.148 Approximately 500 averages should result in rec
dal nerve can be easily activated by placing ring electrodes ognizable and reproducible cortical waveforms. Spinal poten
around the shaft of the penis with the cathode proximal. 148,149 tials may require a sensitivity of 0.5 IJ V/div. This high
There should be several centimeters of separation between the sensitivity necessitates complete relaxation on the part of the
cathode and anode. A stimulus pulse duration of 200 IJS raised patient to minimize muscle artifact.
Reference Data. Very little reference data have been pub
lished (Table 9-22) regarding pudendal SEPs even though this
Table 9-22. Pudendal Nerve SEP Reference Data technique is frequently used with respect to urologic investiga
Latency(ms) tion. 148--ISI As with all other studies, it is recommended that prac
To Peak To Peak titioners develop their own data base from which to judge
abnormality.
Recording Site
MEN WOMEN
CZ' (P37)
TRIGEMINAL NERVE SEP
42.3 ± 1.9 39.8 ± 1.3
CZ' (N45) 52.6 ± 2.6 49.1 ±2.3 In performing trigeminal SEPs, the most common nerve
LI 9.9 ± 1.37 fibers activated are those supplying the cutaneous aspects of the
Filter setting are 5Hz to 250 Hz. From Haldeman et al.'...·I5' face, specifically the sensory divisions of the trigeminal nerve.
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 401
Table 9·23. TrigeminaJ Nerve SEP Reference Data muscle through which the nerves pass forms the so-called tarsal
latency(ms) tunnel. Techniques were developed to evaluate the above-noted
peripheral branches of the tibial nerve to possibly assist in the
To Peak LlR To Peak UR
diagnosis of plantar neuropathies.
Recording Site Stimulation. A constant-current stimulator utilizing a pulse
CS'/C6' (A) 12.5 ± 0.87 (8) 12.8 ± 0.9 0.6 ± 0.5 duration of 200 ~ delivered at 2-3 Hz with an intensity to pro
(N13) duce a moderately vigorous toe twitch of either the first digit
CS'/C6' 18.5 ± 1.51 0.55 ± 0.55 19.3 ± 1.4 0.6 ± 0.4 (medial plantar nerve) or fifth digit (lateral plantar nerve) is
(P19) used (Fig. 9-17).99 A convenient manner of exciting these nerves
C5'/C6' 26.9 ± 2.2 28.6 ± 1.7 1.2 ± 0.8 is with a bar electrode. To activate the medial plantar nerve, a
(N30) line connecting the interdigital region of the first and second toe
Amplitude (IJV) with the heel is bisected.99 The midpoint of this line is where the
N131 2.6 ± 1.1 0.51 ± 0.54 cathode is located, with the anode placed several centimeters
P19 distal. Activation of the lateral plantar nerve is achieved by
forming a similar line between the fourth and fifth digits, and
Filter settings are 2-2000 Hz (A) and 0.5-200 Hz (8). From Stohr et al. 287 (A)
and Eisen et al.'08 (8). the lateral portion of the heeL Again, the half-way point demar
cates the location where the cathode excites the lateral plantar
nerve. The calcaneal nerve is stimulated by placing a bar elec
defined and possibly far-field potentials not representative of trode on the heel a few centimeters plantar to the posterior
trigeminal neural pathway conduction with respect to specific margin of the hee1. 99 The current intensity used for calcaneal
neural structures. stimulation is 3 times the sensory threshold at this region of the
foot. Abrading the skin is recommended for all stimulating sites
MEDIAllLATERAL PLANTAR AND CALCANEAL NERVES because the plantar surface of most feet is calloused.
Additionally, the plantar aspect of the foot contains thick con
The medial/lateral plantar and calcaneal nerves are the three nective tissue, which may impede the passage of current from
terminal branches of the tibial nerve. After entering the ankle the stimulator. Although the medial and lateral plantar re
beneath the laciniate ligament (flexor retinaculum), the tibial sponses should be obtained in all normal persons, the calcaneal
nerve divides into its three terminal branches.154.286 The cal nerve response may be absent because of too much impedance
caneal nerve is a pure sensory nerve that may branch from the on the heel.
tibial nerve just proximal to, or under, the flexor retinaculum to Ground. A ground electrode is located in a convenient loca
provide cutaneous sensation to the heel of the fOOt. 78 The tibial tion such as the sternum or ipsilateral patella.
nerve then terminates in two mixed nerves, the medial and lat Recording Electrodes. The cortical recording electrodes
eral plantar nerves, which supply all of the foot intrinsic mus utilize the same placement as that for the tibial nerve. The
cles except for the extensor digitorum brevis and possibly the medial and lateral plantar, as well as calcaneal SEP waveforms,
first dorsal interosseous (deep peroneal nerve). Each nerve are similar in morphology to all other lower limb potentials.
enters the foot through its own opening in the abductor hallucis Scalp. An E-l recording electrode is placed at CZ', while a
muscle. 141 The medial plantar nerve provides cutaneous sensa E-2 electrode is located at FpZ'. The same montage is used for
tion to the medial aspect of the foot's plantar surface including recording SEPs from all three nerves. Although surface elec
the first three and one-half toes. The lateral plantar nerve sup trodes were used in the original study,99 subdermal recording
plies sensation to the remainder of the foot. The laciniate liga needle electrodes may also be used without a need to alter the
ment in combination with that region of the abductor hallucis recording/stimulating parameters.
Alternate Recordings. Although the original study did not de If two electrodes are located relatively close to each other
scribe spinal potential recordings, it is anticipated that responses and placed in the near-field, one creates a near-field bipolar
should be obtainable. Of course, one would have to establish refer recording montage. Should the E-2 electrode be displaced to
ence data for this location prior to utilizing it clinically. some region of the far-field, a referential near-field montage
Instrument Parameters. An analysis time of 100 ms exists. 189,190,I92-194 This is one way to conceptualize the differ
(sweep of 10 ms/div) and filter settings of 10-3000 Hz are the ence between bipolar and referential recording montages. If
parameters initially used. 99 A sensitivity of 1-2llV/div should both electrodes are relocated to a neural generator's far-field,
suffice for both medial and lateral plantar nerve responses; how interesting results ensue depending upon the two electrodes'
ever, 1 11 VIdiv may be necessary for the calcaneal response, as it location with respect to each other. Two electrodes relatively
is comparatively smaller. A total of 500 averages are adequate close to each other in the far-field region most likely will not
to resolve most responses, but more may be required for partic detect a waveform because the difference in potential be
ularly small calcaneal responses. tween these two locations is negligible. Another way of
Reference Data. The medial and lateral plantar nerves as saying this is to note that if the same potential exists at both
well as the calcaneal response result in typical cortical lower electrodes and differential amplification records only what is
limb SEP potentials.99 Latencies to the initial positive and sub different between the electrodes, the absence of a difference
sequent negative peaks are measured, while the amplitude noted results in no net recorded potentiaL By displacing the two
is from the first positive to following negative peaks (Table 9 electrodes rather distant from each other, but remaining in the
24).99 As only one study has been published to date regarding far-field, a small "far-field" potential may be recorded, partic
these nerves, it is a good idea for the practitioner to replicate ularly if multiple averages are summated to improve the
these data prior to diagnosing pathology. signal-to-noise ratio. Two electrodes in the far-field but dis
tant from each other will detect the small potential difference
between them; however, this difference is small and hence the
SEP APPLICATIONS necessity of averaging multiple trials. It is possible to perform
far-field SEP recordings. .
SEPs have been utilized to investigate many disorders. 39,191.203, The usual technique of clinically recording cortical SEPs is
212,225,278,302,313.317 The wide array of possible diagnostic applica to place both an E-! and E-two electrode on the scalp and
tions can be simplified by considering two major categories in record the potential difference between these two scalp loca
which SEPs may be useful: central nervous system disorders tions, e.g., C3'/C4' and FpZ' for ue.e.er limb studies. 6,7,282 The
and peripheral nervous system lesions. Potential uses of SEPs in result is an easily definable N191P22 potential. By relocating
both diagnostic and prognostic situations regarding central dis the E-2 electrode from FpZ' to the wrist contralateral to the one
orders are explored in detail when both central nervous system being stimulated, the simple N191P22 waveform becomes a
and anterior horn cell disorders are considered (see chapters re rather complex sequential array of positive and negative poten
lated to specific clinical disorders). The diverse applicability of tials preceding the N191P22 complex, which also is somewhat
SEPs with respect to peripheral nervous system pathology is altered.
considered in the remainder of this book when particular dis Specifically, following median nerve wrist stimulation with
ease entities affect various portions of the peripheral nerves. the above noted scalp-contralateral wrist montage, 4 monopha
sic positive potentials are noted (Fig. 9_18).61,62,63.80.81.82,83
SOMATOSENSORY FAR-FIELD POTENTIALS Additionally, the N191P22 complex increases in amplitude and
duration. The larger and longer duration N191P22 waveform is
The electrical field generated by neural tissue may be consid easily understood if one considers the principles of differential
ered to consist of a near-field and far-field. 165,171-173 The near amplification (see Chapter 3).96.98 Two electrodes located rela
field region is that portion of the current distribution in which tively close to a neural generator will, to some extent, share a
the associated isopotential lines change in magnitude with rela certain amount of the data, i.e., these two electrodes will detect
tively small alterations in position within the field, At some some of the same electrical potential. That portion of the elec
point, as one moves away from the neural generator's source tric field that is common to both electrodes is cancelled through
and sink currents, the isopotential field lines change little with differential amplification. The result is amplification of the re
different positions, This region of minimal potential change maining electrical activity. When one of the electrodes is re
may be referred to as the far-field aspect of that neural genera moved to a further location, there is now little electrical activity
tor, A more complete discussion of this topic may be found in in common and the entire potential as observed by the near-by
Chapter 2. electrode is amplified, producing a relatively larger potential
404 - PART II BASIC AND ADVANCED TECHNIQUES
that is also longer in duration. This is the most likely explana for the production of the four early far-field potentials preced
tion for the larger amplitude and longer duration cortical poten ing the cortical response to upper limb median nerve excitation.
tial N19/P22). The observation of 4 positive potentials is The first far-field potential demonstrates a rather consistent
somewhat more difficult to explain. peak at approximately 9 ms and is referred to as the P9 potential
Based upon the above discussion, one can conclude that when (Fig, 9-18), Electrodes located at the axilla and Erb's point,
both electrodes are located on the scalp, the four positive poten median nerve near-field recordings, demonstrated that th~ P9
tials are not observed because they are common to both record far-field potential occurred in time after the corresponding axil
ing electrodes and hence eliminated as a common mode signal, lary near-field potential, but before the Erb's point near-field
i.e., they have the same potential at each of the recording elec potential.63 ,79 The P9 neural generator is, therefore, postulated to
trodes. In other words, the two scalp electrodes are in the far occur in the proximal axilla. Because there are no known
field of four generators that produce the same potential in the synapses or nuclei in this area, the median nerve afferent volley
cranium. By relocating the E-2 electrode to the wrist (any loca itself is the most likely generator. Close inspection of the P9 po
tion will do, as long as it is not on the skull), there is now enough tential revealed that it consisted of two separate peaks in over
of a potential difference between the two electrodes to result in a 70% of individuals, referred to as P9a and P9b.328 According to
recorded waveform even though both electrodes are in the far far-field theory, an alteration in direction of the median nerve
field (see above discussion). By placing the E-2 electrode on fibers as they turned to enter the thorax from the arm results in a
some body part other than the skull, a so-called referential mon dipolar moment imbalance of current associated with the action
tage is created.192-194 The question then becomes, what are the potential.88,112,173.182 This imbalance in dipole moments is de
neural generators producing the four positive far-field potentials? tected by the differential amplifier as a difference in potential
This rather straightforward question unfortunately does not between the two referentially located electrodes producing an
have a simple answer. The full understanding of the mechanism observable waveform. The change in median nerve direction
underlying far-field potential production continues to elude in yields two far-field potentials, one within the axillary region
vestigators, but a few working models do exist (see Chapter 2). (P9a) and a second potential just distal to Erb's point (P9b).
A multitude of neural generators have been proposed to account A second far-field potential is observed at about 11 ms fol
lowing median nerve stimulation utilizing a referential montage
and is known as pIT (Fig. 9-18). A number of neural generators
have been postulated to produce this potential, including synap
tic and post-synaptic activity in the nucleus cuneatus and medial
lemniscus. 13 .14,63,79.182 Considering the conduction velocity of the
traveling neural volley, it has been suggested that this far-field
A Pz-Hand potential arose where the nerve root entered the spinal
cord. 189.289,322 The true generator of the pIT potential remains
controversial.
The third positive far-field potential following median nerve
wrist stimulation has a latency of 13 ms; hence the designation
P13 (Fig. 9-18). Multiple neural generators have been postu
B Scalp-K lated such as the synaptic and post-synaptic activity in the thala
mus, brain stem, medial lemniscus, cerebellum, and ventral
posterior thalamus. I1,63,79.166,275,316 Calculating the distance trav
eled by a neural impulse based upon averaged conduction ve
C TS-It locities suggests that the site of origin for P13 is within the
cervical-E'inal cord. 189 Agreement does not exist as to the most
likely PI3 neural generator.
An inconsistently observed fourth monophasic positive far
field potential, P14, has also had a number of possible genera
D Tl1..Jt tors (Fig. 9-18). Various sites of origin for this potential include
medial lemniscus, cerebellar connections, thalamocortical radi
ations, and the cerebellum. 13,14,79,165,316 As with the two previous
far-field potentials, pIT and P13, the region of nervous tissue re
sponsible for P14 is unknown.
Tibial nerve stimulation also revealed 4 positive far-field po
tentials when recorded with a referential scalp montage. The po
E Gluteus-It tentials have been designated P17. P24, P27, and P31 (Fig.
9_18).79,85,87,209,210.323 Postulated but by no mean accepted sites of
origin for these four respective potentials are: just distal to the
Figure 9-1B. Far-field potential: Median nerve SEPs. (A) Far sacral plexus, impulse entry into the conus medullaris. rostral
field SEP recording following median nerve wrist stimulation. Four spinal cord, and brain stem. 323 Additional work is required re
positive far-field potentials are recorded: P9, pIT, PD, and P14. (B-E) garding both upper and lower limb far-field potential production
Stimulation of the tibial nerve with a cortical referential montage to before its nature and site of origin can be fully understood.
the contralateral knee (K) demonstrating far-field potentials and their
development from the gluteal fold region along the spinal column to Clinical Utility of SEP Far-Field Potentials
the scalp: P17, P24, P27, and P3I. (Modified from Desmedt et al.,79 and A number of investigations have attempted to clinically eval
Yamada et al. 323 ) uate patients' lesions based upon SEP far-field findings. 13 .65 ,71
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 405
The most current thinking on the origin of far-field potentials is coma.33.124.161.332 Specifically, bilaterat,absence of cortical re
that an action potential undergoes a dipolar imbalance when an sponses (BACR) to median nerve stimulation is usually associ
alteration in the surrounding volume conductor's conductivity ated with a very poor prognosis. Studies have shown that, in
occurs (see Chapter 2).88,112,173 A dipolar imbalance may also be patients with nontraumatic encephalopathy, essentially com
produced when an action potential crosses the boundary be plete cortical necrosis is required to obliterate the cortical re
tween two body segments of different size or a nerve impulse sponse.256 Accordingly, the complete absence of SEP responses
changes direction. Finally, if an action potential encounters the indicates a poor prognosis for recovery from coma.
termination of active tissue such as the end of a nerve, a far-field
potential can be seen. Because far-field potentials do not have Median Nerve SEP Methodology
specific anatomic neural generators but depend upon joint posi The literature documents the use of median nerve SEPs for
tion or other variables,84,192,193 their latency and amplitude may predicting prognosis in coma. Although other nerves may pro
vary in less than predictable ways. As a result. it is recom vide similar information, the median nerve-generated cortical
mended that far-field potentials not be used for clinical diagnos SEP response is usually the most robust of all mixed-nerve
tic purposes until such time that more is understood about SEPs.
far-field generation. I 14,192.193.328
Because of this reasonable recommendation, the utilization Stimulation
of additional channels for referential montage recordings must Since patients are comatose, a motor twitch threshold is uti
be questioned. I 10.115 It is certainly acceptable to apply referential lized for setting stimulus intensity because sensory thresholds
recording techniques to experimental situations in the hope of are not useful. Typically, 1.5 times the motor threshold is used.
obtaining more information about far-field potential generators. As previously noted, stimulus rate influences the amplitude of
Utilizing noncephalic referential SEP montages effectively in the cortical response, where faster rates reduce the amplitude.
creases the noise of the trace, as common mode rejection is re For example, in normal subjects, the cortical amplitude with 6
duced and additional potentials are included from poorly Hz stimulation is about 85% of that with 3 Hz stimulation.
understood far-field generating sources. It is recommended that Thus, to compare with published studies, a consistent stimulus
the beginner initially refrain from performing noncephalic ref rate is required. For short-latency studies, most authors use a 2
erential montages and use primarily bipolar (scalp-scalp: FpZ' Hz stimulation rate, while for long-latency studies, approxi
as the E-2 for C3'IC4' and CZ') electrodes placements. Spinal mately a I Hz stimulation rate is used.
referential montages (e.g., TI2-iliac spine), however, may be of
some assistance because the rather small bipolarly recorded Recording
spinal potentials (TI2-TIO) are increased in magnitude and When studying patients with coma to ascertain prognosis, it
hence easier to detect with a referential montage. is extremely important to avoid a false-positive prediction of
nonawakening, i.e., saying someone will not awaken when they
might. False-negative predictions (i.e., saying someone might
PROGNOSTICATION OF CENTRAL awaken when they do not) are more acceptable, since patients
NERVOUS SYSTEM INJURY are not erroneously removed from life support in this instance.
In order to rely on cortical potentials, a number of recording
COMA EVALUATION sites must be used to ensure that the ascending volley actually
reaches the brain. In the trauma setting, multiple injuries to the
Clinicians caring for comatose patients are continually seek neuraxis frequently coexist. Failure to record the ascending
ing better ways to predict outcome. Methods used for this pur volley could mean that an absent cortical response may be due
pose should be sensitive for predicting nonawakening. More to an undetected spinal cord lesion, and hence, result in an erro
importantly, however, such methods need to be exquisitely spe neous false-positive prediction for nonawakening. Thus, one
cific, i.e., they should not erroneously predict nonawakening typically records from the following sites:
when the patient would actually awaken if supportive treatment 1. Peripheral nerve (axilla or Erb's point)
were provided. 2. Cervical spine (C7 spine-Fz)
A number of methods have been studied for their ability to 3. Brain stem (Fz-mastoid)
predict the prognosis of coma recovery. Clinical assessments 4. Contralateral cortex (C3' or C4'-Fz)
like the Glasgow Coma Scale and the evaluation of brain stem Responses from the first three recording sites above indicate
reflexes offer clear predictive value. as patients with low scores an intact neuraxis up to the brain stem. Unrecognized spinal
generally do worse than those with higher scores. However, cord injury and atlanto-occiptal dislocation in patients with
some patients with very low scores ultimately awaken, making traumatic brain injury referred for coma evaluation have been
the information not reliable enough to use for decisions regard detected by using these methods.
ing withdrawal of life support. Recently. creatine kinase BB Sufficient amplification, averaging, and analysis time are all
band levels in the cerebrospinal fluid (CSF-CK) have been necessary to avoid missing an otherwise present response.
shown to indicate a uniformly poor prognosis when sufficiently 'TYpically, at least 250-500 responses for each trial should be
elevated in patients with anoxic encephalopathy.183,301 This tech averaged. depending upon the level of background noise. A dis
nique, however, is not particularly sensitive for detecting non play sensitivity of 0.2-1.0 !lVIdiv is used, and analysis times
awakening and is not applicable in patients with coma due to vary from 50 to 200 ms, depending upon whether short- or long
trauma, since even focal trauma will release CSF-CK. latency responses are evaluated.
A number of electrophysiologic methods have been studied
for their ability to predict outcomes in comatose patients. Of Assessment
these methods, median SEPs have some of the strongest evi Although there are a variety of parameters that can be measured
dence to suggest their utility in predicting outcome after from cortical responses, including absolute latencies, interpeak
406 - PART II BASIC AND ADVANCED TECHNIQUES
A B c
.. . • II •
~
IvY
..
~
IvY
..
~
'fIN
..
, .. ,vY
5vY I fIN
Figure 9-19. SEP examples in patients. A shows a normal left median nerve somatosensory evoked potential (SEP) recorded from a co
matose patient who did not awaken. The first tracing is (active-reference) the C4'-Fz; the second tracing is the mastoid-Fz; the third tracing is the
C7 spine-Fz: and the fourth tracing is the axilla-shoulder. B shows a left median nerve SEP recorded from a comatose patient who did not
awaken. The cortical response is absent. Note the inverted mastoid response in the top tracing: this should not be confused with a cortical re
sponse, since the latency is too early. The first tracing is (active-reference) the C4'--Fz; the second tracing is the mastoid-Fz; the third tracing is the
C7 spine-Fz; the fourth tracing is the axilla-shoulder. C shows a left median nerve SEP recorded from a comatose padent who did awaken. The
cortical response is present and robust, and the N3 (N70) is present. Note the slower sweep speed (20 ms/div) compared with the earlier figures
at 5 ms/div.The first tracing is (active-reference) the C4'-Fz.
latencies, and amplitudes, only a few have been shown to have to be sure that the stimulus actually reaches the brain. As indi
clinical relevance. The strongest indicator of a poor prognosis is cated above, recordings should be made from the peripheral
a bilateral absence of the short-latency cortical response with nerve, cervical spine, and brain stem. In the presence of a sig
median nerve stimulation. To the authors' knowledge, no adult nificant abnormality at any of these sites, the prognosis for
patients with nontraumatic coma, and very few adult patients awakening cannot be stated confidently. Specific lesions that
with coma of traumatic onset (about 6%), ever awaken in this may interfere with recording at these subcortical sites include
setting; of those who do awaken, most have been reported to peripheral nerve lesions or polyneuropathy, brachial plexus
have severe disability.332 In some cases, baseline noise or arti injury, spinal cord injury, and brain stem lesions.
fact might obscure a very small response. Thus, for practical Most medications do not obliterate the short-latency cortical
purposes, absence of a response is often defined as potentials response with median nerve stimulation. These responses are
less 0.5 JlV in magnitude. usually easily recordable even under general anesthesia. There
Absolute peak latency, interpeak latency, and amplitude of the is less known, however, about the effect of medications on long
short-latency cortical responses have not been shown to have a latency responses.
strong prognostic significance. Although patients with normal Volume conduction of far-field potentials may also impair ac
SEPs do better, on average, than those with present but abnormal curate recording. At times, the brain stem potential recorded
responses (Fig. 9-19), the level of certainty is not usually be from the mastoid electrode may be volume conducted to the
lieved sufficient to base clinical decision-making on the results. cortical electrodes (Fig. 9-19B). This should not be confused
Recent data suggest that long-latency responses (i.e., greater with a cortical response since the latency is too short (13-14
that 75 ms in the upper limbs) may be of use in predicting out ms) for a cortical response (19-20 ms).
come as well. Two studies have demonstrated that patients with
bilaterally absent N3 or N70 do not awaken.213.277 One study Specificity and Sensitivity
found a cutoff of 118 ms 213 and another 176 ms277 for predicting When detecting nonawakening, the specificity (avoiding
nonawakening; i.e., those with latencies exceeding these values falsely predicting nonawakening) is of greater importance that
did not awaken. sensitivity (correctly predicting nonawakening). Thus, emphasis
is placed on correctly identifying nonawakening. A literature
Pitfalls search was conducted recently to review the medical literature
There are a number of potential pitfalls that may lead to a for all studies reporting the use of SEPs in prediction of out
false-positive prediction of nonawakening. First, it is important come after coma back to 1966. 251
Chapter 9 SOMATOSENSORY EVOKED POTENTIALS - 407
Articles were included if they specified the etiology of coma have a very poor prognosis for awakening. Further life-sustain
(traumatic, nontraumatic, or mixed), specified whether adults or ing measures on.these patients are futile. Patients in coma due
children or both were studied, and specified outcomes sufficient to traumatic injury with BACRs to median-nerve stimulation
to allow designation of either persistent vegetative state have a poor prognosis, with only 5% awakening but a 95% CI
(PVS)/death, or awakening. Methodology for SEPs also needed of up to 12%. These patients should be considered unlikely to
to be sufficiently specified to allow for assurance that standard awaken, and if they do awaken, they are likely to be severely
technical procedures were followed. Only English language ar disabled.
ticles were included. Excluded were single case reports, case
series with less than four patients, and articles not found in peer Traumatic Myelopathy Evaluation
reviewed journals. The authors' search recovered 51 peer-re Clinicians caring for spinal cord-injured patients are inter
viewed articles. ested in seeking better ways to predict outcome. As prediction
Hypoxic-Ischemic Coma (Adults). Of 962 adult patients methods are refined, patients and families could be given more
with hypoxic-ischemic coma who had SEPs performed, 29% information about expected functional outcome. Methods used
awakened. Of these 962 patients, 285 (29%) had bilateral ab for this purpose should be better than current clinical methods,
sence of cortical responses (BACR) to median-nerve stimula i.e., physical examination including strength, sensation, and
tion. All 285 (l 00%) either died or remained in a PVS 0-1.0%. reflex testing.
Of the 677 adults with hypoxic-ischemic coma in whom median As discussed above, SEPs are thought to travel through the
nerve SEPs were present, 41 % awoke (95% confidence interval dorsal column pathways of the spinal cord. Unfortunately, this
{Cl} 37-45%). represents a disadvantage for predicting functional outcome
Coma Due to Intracranial Bleed (Adults). Of 157 adult after spinal cord injury (SCI). The dorsal columns are not only
patients with coma due to intracranial bleed who had SEPs per topographically distinct from the more functionally significant
formed, 21 % awakened. Of these 157 individuals, 72 (46%) had motor pathways, but also have a different blood supply. Thus, it
bilateral absence of cortical responses to median nerve stimula is possible to have marked differences in the level of impair
tion; 71 of 72 (99%) either died or remained in PVS. One ment for descending motor pathways and ascending somatosen
person (1 %) awakened (95% CI 0-4.0%). Median nerve SEPs sory pathways. Clinically, this can be apparent when joint
were present in 85 of the 157 (54%) adults with coma due to in position sense is preserved in the setting of complete paralysis.
tracranial bleed. Of these 85 patients, 38% awakened (95% CI
27-48%).
Traumatic Coma (Adults). Of 711 adult patients with trau SEPS AND PROGNOSIS
matic causes of coma who had SEPs reported, 58% awakened
overall. Of these 711 patients, 226 (32%) had bilaterally absent There is good evidence of a correlation between light touch,
cortical responses to median nerve stimulation. Of the 226, vibration, joint position sense (IPS), and SEPS.30 There is also
twelve (5%) awakened (95% CI 2-8%). Of the 12 who awak good evidence that those with complete or incomplete SCI have
ened, 10 (83% of those who awakened) were reported to have smaller tibial SEP amplitudes than control subjects. 45 However,
severe disability on the Glasgow outcome scale, and, 2 of the 12 there have not been significant differences between those with
(17%) had outcomes better than severe disability. clinically complete versus incomplete SCI when examining
There are a number of caveats and limitations to this review. SEPS.45 Consequently, even in persons with chronic SCI, it is
First, there is always the possibility that reports of people awak difficult to tell the difference between poor outcomes and rela
ening after having BACR were either missed by the literature tively good outcomes using SEPs.
review or that such reports were not published. Studies attempting to predict outcome in patients with acute
Second, there is always the possibility in many of these stud SCI, using SEPs as a predictor, have produced variable results.
ies that a self-fulfilling prophecy existed. Perhaps, once median Li and colleagues,206 studying 36 patients with acute SCI, found
SEPs were noted to be absent, a full effort was not made to sus that the amplitude of the SEP at 2 weeks post-injury (taking the
tain the patient who died before being given an adequate mean ulnar and tibial responses) contributed to the prediction of
chance to awaken. Most authors indicate that SEPs did not in outcome (as measured by Barthel scores at 6 months), adding
fluence their clinical decisions, but subtle influences cannot be more than the clinical examination (Table 9-25) alone.
excluded. In contrast, Katz and colleagues l86 have found that using
Third, the follow-up period varies widely among studies and SEPs offered no added prognostic value when compared with
there could be some late awakeners unknown to the authors. the clinical examination in 57 patients with acute SCI. No pa
While most patients who eventually awaken do so within days tient with a complete SCIon initial physical evaluation ever
to weeks, there are some patients, particularly after traumatic
brain injury, who do not awaken until months after injury. Table 9-25. Predictors of Outcome in Patients
Finally, the SEP records a long segment of the nervous with Spinal Cord Injury
system, form peripheral nerve to brain. It is possible that in some
patients (particularly with traumatic injuries), a second lesion at % Outcome
the spinal cord or brain stem level could have produced absence Predictor rValue Explained PValue
of cortical responses. While most authors typically record from SEP amplitude (mean ulnar .75 56% .0001
subcortical sites to exclude these possibilities, not all do. It is and tibial)
strongly recommended that recordings from peripheral nerve, Joint position sense .64 41% .0001
cervical spine, and mastoid (reflecting brain stem function) be
included in all SEPs performed for prognostic purposes. Motor strength, joint pOSition .87 76% .0001
sense, and pinprick plus SEP
In conclusion, the data indicate that adults in coma due to
amplitude
nontraumatic causes with BACRs to median-nerve stimulation
408 - PART II BASIC AND ADVANCED TECHNIQUES
developed motor return. An initial examination demonstrating 19. Baer RD. Johnson EW: Motor nerve conduction velocity in premamre infants.
Arch Phys Med Rehabil 1965;46:698-704.
incomplete SCI heralded a result of walking or better in 56.4% 20. Bas GA, Cracco JB, Cracco RQ: Scalp-recorded short latency cortical and sub
of incomplete patients with SCI. Both the initial physical exam cortical somatosensory evoked potentials to peroneal nerve stimulation.
ination and evoked potentials were reasonable predictors of fur Electroencephalogr Clin Neurophysiol 1981 ;52: 1-8.
ther motor improvement. Evoked potentials, however, added 21. Baran EM, Daube JR: Lower extremity somatosensory evoked potentials: An
AAEM workshop. Rochester, MN, American Association of Electromyography
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examination in either complete or incomplete SCI patient 22. Barr ML, Kiernan JA: The Human Nervous System (5th ed). Philadelphia, JB
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23. Beall]E, Appelbaum AE, Foreman R, et al: Spinal cord potentials evoked by
can playa significant role in the prognosis of recovery follow cutaneous afferents in the monkey. J Neuropbysiol 1977;40: 199-211.
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means of electrical phenomena. Cbl Physiol 1890;4:473-476.
25. Beck A: Determination of localization in the brain and spinal cord by means of
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26. Beck A. Cybulski N; Further research on the electrical phenomena of the cere
Somatosensory evoked potentials involve a significant bral cortex in monkeys and dogs. Rozpr Wydz mat-przyr 1891;32:369-375.
27. Benita M, Caude H: Effects of local cooling upon conduction time and synaptic
amount of complex neural theory but are relatively easy to per transmission, Brain Res 1972;36: 135-151.
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necessary time to understand the theoretical foundation upon nerve in man. J Neurol Sci 1981;50:299-306.
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412 - PART II BASIC AND ADVANCED TECHNIQUES
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Chapter 10
Magnetic Stimulation of
the Central and Peripheral
Nervous Systems
Lawrence R. Robinson, M.D.
do not experience stimulation of nervous tissue. As described system compared to conventional methods of electrical stimula
below, the intensity of the secondarily produced electrical field tion. What then is the advantage of magnetic stimulation? The
in nervous tissue (and hence the intensity of nervous stimula principal advantage of using a magnetic stimulator lies in the
tion) is related to the rapidity of the change in magnetic field depth of penetration and its ability to penetrate intervening tis
strength. sues regardless of electrical resistance.
Figure 10-1 demonstrates the theoretical drop in field inten
GENERATION OFTHE MAGNETIC FIELD sity with stimulation at the scalp, comparing electrical with
magnetic stimulation applied at the surface; II field strength at
Formation of a brief magnetic pulse used for nervous system each depth is plotted as a percentage of surface intensity. The
stimulation starts within the main unit of the stimulator. A large electrical field drops off very rapidly with depth from the sur
bank of heavy-duty capacitors (which incidentally contribute face of the scalp, in large part due to the electrical resistance of
most of the weight to the unit) are electrically charged. When the scalp, skull, and CSF; most current is shunted along the in
triggered, these capacitors rapidly discharge through a cable tervening tissues before it ever reaches the brain. In contrast,
into a hand-held coil, producing a brief burst of very high cur while the magnetic field also drops off with distance, the rate is
rent (usually several thousand amperes). The current moving slower than for electrical stimulation. Moreover, for all practical
through the hand-held coil then produces a large (in the range of purposes, the type of tissue between the coil and the site of in
1-3 tesla) time-varying magnetic field. One tesla (T), equivalent tended stimulation is irrelevant; the drop-off is essentially the
to 10,000 G (gauss), is much larger than the Earth's magnetic same for air, bone, fat, muscle, saline, etc. Thus, to stimulate
field, which is roughly 5 x 10-5 T. The duration of the current areas of the brain or other deep nervous tissues, it takes a com
flow, and hence of the magnetic field, is very brief; it typically paratively lower surface field strength with magnetic stimula
lasts for only about 50 microseconds, although some stimula tion than for electrical stimulation, i.e., the penetration is far
tors have a decaying sinusoid wave with subsequent smaller better.
peaks. 98 •108 As a result of this brief magnetic field, a secondary As mentioned above, it should be kept in mind that the ab
electric field is produced in nearby tissues or objects that allow solute field strength (in T) is not the most important feature for
current to pass; these in effect act as secondary coils. The stimulation of nervous tissue, but it is rather the rate of change
strength of the electric field produced by this stimulation is re of the magnetic field. Thus, a 2-T stimulator is not necessarily
lated in part to the first derivative of the magnetic flux over time better than a I-T unit and could be worse if it discharges its ca
(dB/dt); the more rapidly changing the magnetic field, the pacitors more slowly. Pulse duration and shape as well as mea
stronger the intensity of the generated secondary electric field surement of induced currents in secondary coils may provide
and the consequent nervous stimulation. The strength of the in more useful information about the intensity of nervous stimula
duced current is also proportional to the conductivity of the tion provided by various units.
medium in which it is generated. Thus, in cerebrospinal fluid a
relatively high current is generated, whereas in osseous struc COIL GEOMETRIES
tures the current is negligible. The induced current has the re
verse direction of the originating current in the coil. A number of different coil geometries have been used for
magnetic stimulation. Generally the tradeoffs in choice of coils
ADVANTAGES OF MAGNETIC STIMULATION involve intensity or depth of penetration vs. focality of stimula
tion. Large diameter (e.g., 9 em) coils produce greater intensity
It is considerably more complicated and expensive to produce fields that penetrate more deeply but stimulate over a wider area
a large rapidly changing magnetic field to stimulate the nervous and are less focal than small-diameter coils. Small diameter
(e.g., 2-cm) coils, in contrast, can stimulate in a more focal fash
Induced Electric Fields (% of Surtace) ion but do not penetrate very deeply or stimulate very intensely.
For some applications, the focality of stimulation is not criti
, Surface Intensity
50.---------~------------------------------- cal since the selectivity of the testing procedure is achieved on
the recording end of the system. When measuring conduction
time of the descending motor pathways supplying the intrinsic
muscles of the hand, for example, one can place recording elec
trodes over the thenar or hypothenar muscles and stimulate over
a large area of motor cortex; although one might stimulate a
large area of cortex, only the events directed toward the hand
muscles are recorded. Additional selectivity also can be
achieved by directing facilitation (see below) to isolated groups
of muscles. In the above example, one can limit facilitation (a
small voluntary contraction) to just the thenar muscles and thus
limit the muscles activated.
20 40 50 80 100
There are, however, situations in which limitation of the area
Depth in mm of stimulation is critical. Mapping studies of the motor cortex
_ Magnetic Stim ~ ElectriC Stim require activating focal areas of the brain. Similarly, isolated pe
ripheral nerve stimulation requires focal magnetic fields to
Figure 10·'. Theoretical drop off in magnetic and electric avoid activating the nerve over a wide area or to avoid activating
field strength at varying depths from the surface of the scalp. adjacent nerves.
Field strength is plotted as a percentage of that applied at the scalp Several different strategies have been directed toward limiting
surface. spread of current in these cases. One may change the orientation
Chapter 10 MAGNETIC STIMULATION OFTHE CENTRAL AND PERIPHERAL NERVOUS SYSTEMS - 417
EQUIPMENT SAFETY
···· ·· ·· ·· •• •• ,, ,, •• ·· ·· ·· ··
0
··
z
As mentioned above, these devices release a very large cur
rent with each stimulation; this is probably several times that re , ·· ···· ·· ·• ,, •
• ·· , · ··· ·•,• ,• ,,•,,• ··· ·· ·· ··
I
quired to be lethal if one were exposed to the current directly. t I
Thus, in addition to safety concerns with respect to patients/sub
jects (see below, cortical stimulation), one should avoid the pos
sibility of injury from exposure to the currents normally
·· · · ·· · • • • ·· .· · ··
handled within the stimulator and coil. Since the capacitors
store and release a very large charge for each stimulation, man
" ·· · ·· ·· ··• ·• • •• •• •• ·· ·· ·· ··
M
t
Figure 10-3. Stimulation of the motor cortex with killed end The pathways these descending impulses take from the cortex
recording from pyramidal tracts in the baboon.A Single cortical are not definitively known. There is, however, evidence suggest
stimulation produces multiple discharges from the pyramidal tracts; ing that they travel via the corticospinal pathways. In cats, it has
the first direct wave (0) is followed by a series of periodic indirect (I) been found that the signal was strongest in the area of the spinal
waves. In the middle trace,l waves are absent as a result of cortical de cord near the corticospinal tracts and in the anterior horn cell
pression from anesthesia, but recover after anesthesia. (From Amassian area. 81 ,82 Lesioning studies have confirmed that most of the
VE, Steward M, Quirk GJ, et al: PhYSiological basis of motor effects of a signal travels in the area of the corticospinal tract. The conduc
transient stimulus to cerebral cortex. Neurosurgery 1987;20:74-93, tion velocity measured in several studies (60-70 m/s) agrees
with permission.) with propagation through fast corticospinal tract axons.
allow resolution of peripheral vs. central slowing. Thus, meth Table 10-1. Mean Values of Magnetic Cortical Stimulation
ods have been derived to subtract peripheral conduction time with Ipsilateral and Contralateral Facilitation of the Target
from the total scalp-to-muscle latency. Muscle (n = 36)
One method is to stimulate with a second magnetic or elec Ipsilateral Contralateral
trical impulse over the cervical or lumbar spine. This probably Activation (SO) Activation (SO)
activates roots distal to the neural foramen (see root stimula
tion below). Needle stimulation is usually required to activate Latency (ms)
the roots when using electrical impulses for stimulation. Cortex-APB 18.9 (1.23) 20.6 (1.20)
Another method uses F-waves elicited from electrical stimula CMCT-APB 5.7 (0.90) 7.4 (0.87)
tion at the wrist or ankle to calculate peripheral conduction Cortex-TA 25.7 (2.0) 27.8 (2.1)
time. 120 While F-waves are probably better at considering the CMCT-TA 14.7 (0.87) 14.9 (0.61)
entire length of the lower motor neuron, they have the disad Normalized amplitude (MEP/M-wave)
vantage of being slowed in some central processes (e.g., sy APB 0.39 (0.13) 0.36 (0.19)
ringomyelia); thus they could lead to an underestimation of TA 0.56 (0.28) 0.30 (0.20)
central conduction times. On the other hand, using magnetic or
CMCT, central moi:or conduction time; SD, standard deviation;APB. abductor
electrical root stimulation in the calculation adds a small pe pollicis brevis; TAo tibialis anterior.
ripheral (proximal) conduction time to the central conduction. Adapted from ZwartS MJ: Central motor conduction in relation to contra- and
Subjects find magnetic stimulation of nerve roots or F-wave iipsilateral activation. Electroencephalogr Clin Neurophysiol 1992;8S:4~29.
tion because of the possibility of movement. There are reports of Thenar 20.04 ± 1.5 46.1 ± 23.5 6.7 ± 1.2
magnetic cortical stimulation producing seizures in seizure =
(N 95) ( 16.8-23.8) (27.8-113.4) (4.9-8.8)
prone individuals; those with a risk or history of seizures should TA 27.7 ± 2,4 34.9 ± 19.7 13.1 ± 3.8"
not have cortical stimulation (see section on safety below). (N = 83) (20.2-32.5) (19.3-87.6) (10.1-16.3)
While kindling of a new seizure focus is a concern with high
Amplitudes measured peak to peak. CMCT, central motor conduction time; TAo
rates of stimulation, kindling has not been induced in animals tibialis anterior; EDC. extensor digitorum communis. Values are mean ± SO
with stimulation frequencies below 10 Hz, despite prolonged du (range). MEP: motor evoked potentials. M: compound muscle action potential;
rations. Although one study demonstrated a high frequency of CMCT: central motor conduction time.
hearing loss in rabbits exposed to repeated stimuli.37 audiologic 'Measured using F response. Mean ages (ranges) of subjects. biceps: 49.5 ± 18.5
(20-83); EDC:54.S ± 16.9 (20-83); thenar: 44.6 ± 16.8 (20-83);TA: 37.9 ± 15.0
Nevertheless, many investigators use hearing protectors during Adapted from Eisen AA. Shtybel W: Clinical experience with trancranial mag
may need to adjust the low-frequency filter accordingly and/or Spinal Cord Injury
consider the use of shielded recording cables. After complete spinal cord injury (SCI), usually no re
sponse can be obtained from muscles below the level of the
USE OF MAGNETIC CORTICAL STIMULATION lesion, while normal responses can be obtained above. One
TO ASSESS DESCENDING MOTOR PATHWAYS group58 has reported very prolonged motor responses from the
IN DISEASE STATES abductor pollicis brevis in a few clinically complete C5 Or C6
lesions, suggesting that subclinical sparing of motor tracts
Multiple Sclerosis may occur in some patients. This finding, however, is not com
monly reported.
There are a number of disease states in which magnetic corti MEPs and SEPs have been studied after inducing spinal cord
cal stimulation has been applied. Multiple sclerosis (MS), a de injury in cats.82 The MEP recorded below the lesion was the
myelinating disease of the central nervous system, is a condition most sensitive indicator of injury. On follow-up, the MEP re
in which slowing of central motor conduction time (CMCT) is sponse always returned before the animals started ambulating,
commonly reported. A number of studies have documented pro although this was often only 1-2 days before. No cats without a
longed CMCTs in patients with MS, consistent with demyelina response started to ambulate again.
tion of motor tracts.13.38.66,67,IOO,134 Some evidence suggests that Perhaps the most useful application of MEPs in patients with
MEPs are more sensitive than SEPs, with an overall incidence SCI is in detecting new neurologic compromise. There are data
of abnormality of slightly more than 70%. In a study of 83 pa suggesting that MEPs reflect the degree of descending motor
tients with definite or probable MS recording the response from tract impairment in posttraumatic syringomyeJia;86 patients with
abductor digiti minimi (ADM), responses were of very pro weakness or progressive neurologic deficit usually show a pro
longed latency; amplitudes were often reduced as well. 67 longation of CMCTs. We have also noted improvement in
Abnormalities in MEPs correlated well with brisk finger flexor CMCTs after successful decompression of posttraumatic
jerks, The incidence of electrophysiologic abnormalities com syrinx,86.87.l21 although this finding has not been universally re
paring the various evoked potentials was: MEPs 72%, VEPs ported. 97 Mapping studies (see below) also have been of interest
67%. SSEPs 59%, and BAERs 39%. In comparison, MRI of the in demonstrating changes in the motor cortex after spinal cord
brain has sensitivities of 80% or more. injury.
There is also some evidence that the degree of abnormality
on central conduction times is associated with the degree of dis Stroke
ability. In a study of 45 patients with multiple sclerosis, the pro A number of studies have looked at motor evoked potentials
longation in CMCT (from head to cervical region) correlated in patients after stroke, primarily to evaluate prognosis. In a
with the level of disability.9 study of 20 patients with chronic hemiparesis or hemiplegia, on
Others 74 have also found a good correlation between disabil the affected side, 15 patients had no response in either the APB
ity and CMCTs. Moreover, they found that patients who im or biceps brachii, 2 patients had an absent response in one
proved on steroids had a concomitant shortening in CMCT, muscle, and the remaining 3 patients had delayed responses. 14
while those who had no improvement had stable CMCTs. There was no clear correlation between electrophysiologic ab
normalities and clinical deficits; no responses were recorded in
Cervical Spondylosis some patients who had voluntary movement.
Cervical spondylosis is a very common cause of myelopathy In a study of 19 patients with recently completed stroke,
in the elderly. 19.20.77,79 While imaging modalities (CT and MRI) delays in CMCT were found predominantly in subcortical le
can detect cervical spondylosis and compression of the spinal sions, whereas those with severe cortical strokes were more
cord, these changes may be seen only in the presence of a severe likely to have absent MEP responses. 93 It was also found that
neurologic deficit. 78 •79 patients with preserved MEPs had smaller infarcts on CT and
MEPs recording from the thenar and the tibialis anterior that MEPs had a slightly better predictive value for functional
muscle appear especially sensitive for detecting myelopathy prognosis than SEPs. Cortical MEPs were present in 9 of 10 pa
secondary to cervical spondylosis,l whereas patients with tients who made some degree of functional recovery, whereas
radiculopathy alone are generally reported to have normal they were absent in 8 of 9 patients who made no recovery or
MEPs. Other muscles also can be useful in determining which died.
spinal cord levels are most affected. 27 Some evidence suggests Another study has evaluated 33 patients within 3 days after
that MEPs may be more sensitive than SEPs, possibly because stroke. 45 Two months later, those with present or prolonged
cervical spondylosis (often with prominent bony spurs project MEPs had improved motor function compared to those without
ing from the vertebral bodies) predominantly involves the an responses. MEPs may be somewhat predictive of recovery from
terolateral quadrants of the spinal cord. This could potentially dysphagia, in that those with larger increased pharyngeal repre
affect descending motor tracts in the corticospinal tracts, leav sentation in the unaffected hemisphere have a better recovery,
ing dorsal column pathways relatively unaffected. suggesting a role for the intact hemisphere reorganization in re
In one report of 67 patients with cervical spondylosis, covery.62 The largest study on 118 first-ever stroke patients stud
CMCTs were prolonged in 84% of patients with radiologic evi ied the natural history of MEP changes following stroke and the
dence of cord compression and in 22% of those without. 96 These predictive value of MEP responses. 64•65 It was shown that the
MEP abnormalities correlated well with upper motor neuron presence (delayed or normal) or absence of a response follow
Signs. Postoperatively, however, no improvement in MEPs oc ing magnetic cortex stimulation on day 1 had a strong correla
curred. In another study of subjects with asymptomatic cervical tion with outcome after 12 months. Thus, clear prognostic
spondylosis, the majority of such patients (92%) had normal information can be obtained from MEPs in patients with stroke,
MEPs, suggesting that in the absence of clinical manifestations even in a very early stage. It is not yet clear how this compares
MEPs are likely to be normal. 138 with information from clinical assessment alone.
Chapter 10 MAGNETIC STIMULATION OFTHE CENTRAL AND PERIPHERAL NERVOUS SYSTEMS - 421
Motor Neuron Disease Nevertheless, there are some reports of magnetically acti
As would be expected, MEPs are abnormal in motor neuron vated MEPs being successfully used for monitoring of invasive
disease. 41.103 Abnormalities include absence of a response, pro procedures. There is one report, for example, of MEPs recorded
longation of latency, and, most commonly, low-amplitude motor from the distal limb muscles in response to transcranial magne
responses. Slowing is thought to reflect dropout of faster-con toelectrical stimulation in 10 patients during embolization of ar
ducting axons, rather than demyelination, whereas amplitude teriovenous malformations. 123 Stable potentials in 8 of 10
changes may reflect either loss of anterior horn cells, cortico patients coincided with an uneventful neurologic outcome,
motorneurons or both. while prolongation of the CMCT in 2 patients coincided with
MEPs may be relatively sensitive for detecting upper motor transient hemiparesis, probably caused by ischemia.
neuron abnormalities in patients with motor neuron disease. For At this point it remains too early to know if magnetic stimula
instance, one group found that MEPs revealed evidence of tion of the motor cortex will be as reliable as other techniques
upper motor neuron dysfunction in 84 of 121 (69%) patients for intraoperative assessment and whether technical difficulties,
with motor neuron disease, including unsuspected upper motor particularly if effects of anesthesia, can be overcome.
neuron involvement in 6 of 22 (27%) patients who had purely
lower motor neuron syndromes clinically.l40 Increased MEP MAPPING AND ASSESSMENT OF
threshold was the abnormality observed most frequently. CORTICAL REPRESENTATION
Similar findings have been reported by others. 104
Measuring the areas representing various muscles or move
INTRAOPERATIVE MONITORING ments can be of interest both for the study of cortical physiol
ogy in normal subjects and for examining plasticity and other
The idea of using motor cortex stimulation during spinal processes after neurologic perturbations.
surgery is conceptually appealing for several reasons. First, the In animals the areas of motor cortex corresponding to various
most functionally significant impairments after intraoperative movements or muscle contractions have been studied in a vari
iatrogenic myelopathies are probably related to the resulting ety of species. 34 Typically, electrical pulses have been applied to
motor deficits; thus it would be useful to monitor these descend the exposed cerebral cortex and the resulting movements either
ing motor tracts directly. Second, due to the anatomy of the directly visually observed or recorded via EMG. While EMG
spinal cord blood supply, it is at least theoretically possible to recording is often used to record single muscle activity after
infarct the anterior two thirds of the spinal cord (via compro cortical stimulation, it should be noted that, at the cortical level,
mise of the anterior spinal artery) and preserve SEPs that ascend the organization is more "movement-specific" rather than
through the posterior columns. muscle-specific; thus there are probably multiple overlapping
Levy et al. were among the first to report on using MEPs to areas of the cortex representing each muscle. 71 Nevertheless, be
monitor the descending motor tracts during surgical procedures. cause of ease of recording and quantification, EMG recording
They reported on 98 cases of MEP monitoring with electrical of individual muscles is still used.
stimulation during neurosurgical procedures. so•s3 They found Despite the fact that mapping studies had been performed in
that the peripheral nerve response during monitoring was much mUltiple animal models over the last 100 years, mapping of the
more sensitive to injury than the spinal cord response. Rever human cortex had been generally limited to stimulation of the
sible loss of the peripheral nerve signal was not associated with exposed (usually abnormal) brain during surgical procedures. It
a postoperative deficit, suggesting that MEPs could be of value has only been through the advent of surface stimulation, at first
for intraoperative monitoring. electrical and now magnetic, that investigators could noninva
One technical problem with using MEPs in the operating room, sively map the motor cortex both in healthy individuals and in
however, has been the effects of anesthesia. Recent studies46 those with diseases or lesions. Surface electrical stimulation
demonstrated a 60% reduction in MEP amplitude to the abductor was used initially and potentially offers the advantage of more
digiti minimi with the administration of midazolam and fentanyl. focal stimulation than magnetic coils. However, with the devel
Another groupl48 has reported an average reduction of MEP am opment of more focal coils (e.g., the butterfly coil), the rela
plitudes to about 10% of preoperative values during anesthesia tively painless technique of magnetic stimulation has become
with nitrous oxide and fentanyl. Normal volunteers breathing ni widespread.
trous oxide alone had a similar marked reduction. Intravenous nar There are two alternative approaches to mapping the cortex
cotics (fentanyl, flunitrazepam, and thiopental) have had more with magnetic coil stimulation. 32•61 One technique maps out
moderate reductions in amplitude (30-50% reduction), but it is not stimulation thresholds, i.e., the center of the "map" for a given
practical to use these agents alone for the majority of neurosurgi muscle has the lowest threshold for activation (usually mea
cal or orthopedic cases; doing so carries the risk of requiring pro sured in percent of maximum output of the stimulator), with in
longed ventilatory support. In monkeys, use of etomidate has creasing thresholds as one moves out away from the center.
permitted MEPs to be recorded under anesthesia, but latencies are Because it can be difficult and time-consuming to measure
significantly prolonged (up to 10%) and amplitudes reduced (up to thresholds, this has not been the method of choice. The alterna
60%), making it of questionable value for sensitive monitoring. 56 tive method uses a standard stimulus intensity somewhat above
Enflurane or isoflurane alone also markedly reduces MEP ampli threshold and maps the amplitude of the EMG muscle response
tudes, even in subanesthetic concentrations.26.135 with stimulation over various sites; thus the center of the "map"
These problems largely do not exist with electrical. as opposed has the largest-amp1itude EMG response. The second method is
to magnetic, stimulation of the brain or spinal cord. 141 Some au quicker and more commonly used, but it is not yet clear how the
thors have reported using electrically activated motor evoked p0 two methods compare.
tentials intraoperatively; one group,I49 has reported recording Results of mapping the motor cortex in normal subjects have
from spinal cord and cauda equina. Of 40 patients, there were re been reported32.33 and are similar to those obtained with stimula
portedly no false negatives, 3 true positives and 5 false positives. tion of the exposed corteX.116.145 For the upper limb, distal muscles
422 - PART II BASIC AND ADVANCED TECHNIQUES
are represented more laterally than proximal muscles, e.g., the tourniquet are mapped, they demonstrate an increase in MEP
site for activating intrinsic hand muscles is about 7 cm lateral to amplitude within minutes. The time frame of these findings
the midline, while the biceps brachii is more medial, about 5 cm again raises the possibility of unmasking of established path
lateral to midline. Lower limb muscles are represented closer to ways. The duration of these changes in amputees has been re
the midline (near C z). ported to last more than 20 years post-amputation. 124
In general, responses are recorded only contralaterally; however, Even in normal subjects, some changes in motor maps cal). be
occasionally for proximal upper limb muscles we have recorded ip induced. Focal transcranial magnetic stimulation has been used
silateral responses, possibly from uncrossed corticospinal path to examine the effects of 120 synchronized thumb and foot
ways (unpublished observations with Dr. Greg Malloy). movements on the motor output map of the right abductor polli
Perhaps the most interesting capability provided by mapping cis brevis (APB) muscle. 84 The center of gravity (CoG) ofthe
techniques is the opportunity to noninvasively examine changes output map moved medially in the direction of the foot repre
in cortical representation after a perturbation, i.e., neuroplastic sentation area (mean movement 7 mm ) and returned to its orig
ity. This has been examined in a number of circumstances. inallocation within 1 hour after the experiment.
After spinal cord injury (SCI), muscles immediately rostral to
the level of the lesion have been examined and mapped. 36•136 INHIBITORY PHENOMENA
These investigations have demonstrated plastic changes in the
motor cortex after SCI; muscles rostral to the lesion (e.g., biceps While most of the preceding discussion has focused on exci
brachii in C6 quadriplegia) have enlarged territories compared tation of muscles resulting from stimulation of the motor cortex,
to control subjects. These changes may be seen within days there are a number of interesting inhibitory phenomena reported
after onset of SCI, raising the possibility that they represent un as well. These events have been produced from stimulation of
masking of established pathways rather than development of the motor areas of the cortex as well as other remote areas (e.g.,
new anatomic connections. It is unclear what implications these occipital cortex).
changes have for treatment or spontaneous recovery of function. Silent periods induced by stimulation of the motor cortex prob
Patients with peripheral nervous system lesions are reported ably represent one type of inhibitory phenomena. Silent periods
to have changes in cortical representation as well. Patients with are easily observed when a subject exerts a maximal voluntary
prior polio, for example, have smaller cortical areas in muscles contraction in a target muscle (e.g., APB) and a magnetic stimulus
affected by polio compared with the analagous muscles in the is applied over the contralateral motor cortex; one will record a
contralateral limb. lIO silent period during which the subject cannot continue or restart
Similar changes are reported in patients with amputations. In the contraction for up to a few hundred ms (Fig. 10-4). The silent
subjects with traumatic, surgical, or congenital amputations, period varies from one muscle to another but can last for up to 300
muscles just proximal to the amputation have enlarged maps.35 ms in the thenar muscles; 122 the duration is proportional to the size
Some of these changes probably occur very early. Brasil-Neto of cortical representation (e.g., longer in hand muscles than more
and colleagues 21 have cleverly mimicked the early changes proximal muscles), and to the intensity of magnetic stimulation.
after amputation by using an inflatable double tourniquet. which Silent periods may be altered in some disease states. They
produces anesthesia distally. When muscles just proximal to the have been reported to be prolonged in patients with hemiparesis
and shortened in those with Parkinson's disease. 63 Shortened
ECI
silent periods have been found after stroke, ALS, and cervical
StlDI,CIIAP Silent Period
myelopathy.143
Inhibitory effects produced from stimulating areas of the
cortex corresponding to language have also been observed. Using
I
special prototypical stimulators, application of rapid (25 Hz)
magnetic stimulation to the dominant side produced temporary
speech arrest. 111 These findings are of special interest because of
the potential ability to quickly determine in a noninvasive way
!
Figure 10-4. Silent periods recorded from the abductor pol.
mation. When healthy subjects are presented with three letters
(a trigram) for 14 ms on a computer screen, they can remember
and repeat these three letters with essentially perfect accuracy.
However, when a magnetic stimulation is applied over the oc
cipital cortex 40 to 120 ms after the trigram is presented, there
is significant impairment in the identification of the letters,12
lleis brevis. The subject is asked to sustain a maximal voluntary con i.e., the letters are "forgotten."
traction during which a magnetic stimulation is applied to the
contralateral motor cortex. Despite repeated trials, silent periods of
up to 300 ms are reliably produced. ECS. electromagnetic cortical STIMULATION OF THE PERIPHERAL
stimulation; CMAp, compound muscle action potential. (From NERVOUS SYSTEM
Robinson LR, Goldstein BS, UttIe JW: Silent periods after electromag
netic stimulation of the motor cortex. Am J Phys Med Rehabil When first developed, magnetic stimulators were thought to
1993;72:23-28, with permission.) hold promise for use in the peripheral nervous system (PNS) as
Chapter 10 MAGNETIC STIMULATION OFTHE CENTRAL AND PERIPHERAL NERVOUS SYSTEMS - 423
well as the brain. The potential advantages were thought similar have been no successful reports of activating the cervical spinal
to those applicable to cortical stimulation: deeper penetration of cord with magnetic stimulation, i.e., subjects do not demonstrate
stimulation and less painful stimulation. However, in contrast to lower limb movement or report upper limb paresthesias.
cortical stimulation, there are already very well established, When applying magnetic stimulation over the cervical spine,
broadly accepted methods for stimulating peripheral nerves, depolarization probably occurs at the root distal to the interver
namely electrical stimulation. Despite initial hopes, magnetic tebral foramen rather than within the spinal canal itself.24,52,109
stimulation has demonstrated a number of disadvantages that There are several lines of evidence supporting this hypothesis:
have made it far less useful in the peripheral nervous system (1) comparison with direct electrical root stimulation suggests
than initially thought. that the point of stimulation (in the cervical area) is about 7 cm
Perhaps the biggest problem with the magnetic coil is the distal to the intervertebral foramen;lIs (2) comparison with F
lack of focality of the stimulation. As opposed to many applica wave latencies suggests the depolarization point may be about 7
tions of cortical stimulation, peripheral nerve conduction stud cm from the anterior hom cell;24 and (3) modeling of current
ies require knowing the precise site of stimulation as it is critical flows from magnetic stimulation over the spine have shown that
to accurate measurement of latency and conduction velocities. the greatest current densities are in the area of the intervertebral
A number of studies have documented that several centimeters foramen (Fig. 10_5).49,89,91 The latencies of electrical and mag
of nerve length near the coil are usually depolarized and that the netic root stimulation were not significantly different, suggest
site of stimulation is variable from one stimulation to the ing an identical excitation site. Since there is no clear shift in
next. 108,109 Moreover, the site of stimulation for different fiber latency with higher magnetic stimulus strength, a preferential
populations may differ with magnetic stimulation; larger fibers site of excitation is postulated, probably at the neurofora
are probably stimulated at a greater distance from the coil than men. 50.53.142 It has also been shown that even with low magnetic
smaller fibers, producing a greater degree of temporal disper stimulus strengths, it is possible to excite sensory root fibers and
sion than with corresponding electrical stimulation. 40 While record antidromic sensory potentials with ring electrodes at the
changing the orientation, shape, or size of the coil may reduce fingers. lSI
the area of stimulation or its variability, the precision obtained For magnetic stimulation of the roots to become well ac
with this technique is still not nearly as good as for its electrical cepted, it will need to be shown to be as good as, or superior to,
counterpart.109 electrical root stimulation; the latter has been well described
Not only are latencies and velocities difficult to accurately and is clinically useful in the evaluation of plexopathies and
determine with magnetic stimulation, it is also difficult or im proximal nerve lesions. 95 While electrical stimulation requires
possible to supramaximally stimulate a single peripheral nerve needle insertion and sometimes high (uncomfortable) voltages,
without simultaneously activating nearby nerves. 28,S 1 Thus, am
plitudes of peripheral nerve responses have been less than those
with electrical stimulation and volume conduction to other
nerves has been frequently reported.
Nevertheless, there remain some potentially useful applica
tions of magnetic stimulation of peripheral nervous system that
are still being investigated. Phrenic nerve conduction studies
usually require high levels of electrical stimulation and may be
more easily performed with magnetic stimulation. s8 Facial
nerve studies also may be performed with magnetic stimula
tion. l46 With surprisingly low stimulus strength it is possible to
stimulate the peripheral part of the facial nerve within the skull
by positioning the coil over the parieto-occipital area. 57,S9,125,126,133
It is also possible to stimulate the motor cortex and measure the 200
central conduction to the facial muscles. Recording from the
nasalis muscle usually gives a clear, biphasic CMAP.I25 With 1601
magnetic stimulation the facial nerve is probably excited at the
120
transition of cerebrospinal fluid to bone in the facial canal (the
labyrinthine segment). Comparing the latency with electrical 80
mVlmm
stimulation at the stylomastoid foramen results in a transosseal
conduction time (average 1.3, SD ± 0.15 ms),125 This technique 40
provides the opportunity to asses the localization of an acute
mV/mmt 0
conduction block of the facial nerve such as in Bell's palsy. It
has been shown that an absent response at the first day predicts
-40
a poor recovery. 118,1 19 It is also possible to differentiate an in mm 0 4 8 12 16 20 24 28 J2
franuclear from a supranuclear facial nerve lesion. l44 Magnetic
stimulation to other cranial nerves and muscles is also feasible, Figure 10-5. Voltages measured across neural foramen at
for example the lingual muscles. lOS the T2-T3 level during magnetic coil stimulation. The highest
voltages are measured within the foramen (point H). The lower trace
STIMULATION OVER THE SPINE AND NERVE ROOTS demonstrates the first spatial derivative of the electric field. (From
Macabee PJ.Amassian VE. Eberle LP, et al: Measurement of the electric
A number of studies have examined the possibility of stimulat field induced into inhomogenous volume conductors by magnetic
ing over the spine using magnetic stimulation in order to evaluate coils: Application to human spinal neurogeometry. Electroencephalogr
the roots and proximal PNS.I09 To this author's knowledge, there Clin Neurophysiol 1991 ;81 :224-237, with permission.)
424 - PART II BASIC AND ADVANCED TECHNIQUES
it has the advantages of producing supramaximal stimulation. before and within 30 minutes after magnetic cortical stimulation
The advantage of magnetic stimulation is that it is relatively (mean of 35 stimuli), there was no change in EEG, verbal
painless. BI When the amplitude of the respons is not an impor memory, language fluency, visual memory, attention, or grip
tant item. magnetic stimulation seems preferable and can show strength. 22,23 While one group has reported that maximal mag
focal conduction slowing in the proximal parts of the peripheral netic stimulation can produce a mild change (10%) in short-term
nervous system. It is already an acknowledged technique for memory. it is the same with stimulation over the cortex or c~rvi
measuring the peripheral conduction time in order to calculate cal spine, suggesting this might not be a cortical effect. 54 Rapid
the conduction in central motor pathways.13 Several reports rate transcranial magnetic stimulation (stimulation frequency> 1
have shown delayed responses in lumbar root disease and plex Hz) can induce significant side effects, such as temporary hear
opathy.7,29.30.94.144 It is also suggested that the latencies of mag ing threshold changes and seizure provocation; guidelines for
netic root stimulation could replace F response determinations preventing unwanted side effects have been suggested. l13
because it is easier and faster to perform. 24 Further. if F re
sponses are absent due to disease. it is often still possible to
obtain magnetic evoked root responses. One study used the la CONCLUSION
tencies of cervical and lumbar root stimulation to assess the
homogeneity of peripheral conduction in generalized (polyneu Magnetic stimulation holds promise primarily with respect to
ropathies). focal (lumbar stenosis). and multifocal (inflamma its ability to noninvasively activate areas of the brain. Potential
tory demyelinating polyneuropathy) disease.152 However, more clinical applications include study of multiple sclerosis, spinal
studies are needed to investigate the place of this promising cord injury or other types of myelopathy, and stroke.
technique in the work -up of peripheral nerve disorders. Intraoperative monitoring may be an application if effects of
anesthesia can be adequately controlled. Interesting research ap
plications include cortical mapping. study of neuroplasticity, as
SAFETY CONSIDERATIONS well as study of inhibitory phenomena. Applications regarding
the peripheral nervous system concern the easy stimulation of
Although magnetic stimulators have been approved for use in several cranial nerves at their intracranial course and the rela
the peripheral nervous system, they are not yet FDA-approved tively painless root stimulation, providing the opportunity to
for cortical stimulation. In addition to some of the concerns assess proximal conduction.
about the electrical safety to the user mentioned earlier, there
are still a number of concerns about the safety of providing this
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Chapter II
HISTORICAL BACKGROUND used, but these reports account for only a small fraction of the
literature. For instance, cutaneous pressure can be quantified to
Over 25 years have passed since quantitative sensory test some extent with simple instruments, such as the graded
ing (QST) was introduced in human subjects.3() Since this first Semmes-Weinstein monofilaments popularized in the evalua
report, a variety of QST instruments have been developed, and tion of patients with Hansen's disease. Electrical current per
investigators have applied QST to a wide range of disorders af ception, where sensory receptors are bypassed and axons are
fecting sensory function with varying degrees of success.92 In directly depolarized by an electrical current, has also been stud
most disorders, including peripheral neuropathies with sensory ied,J3.61 but questions regarding the reliability of this approach
involvement, investigative work is predominantly descriptive, remain. 53
providing the rate of abnormalities to a particular sensory The advantages of thermal and vibratory stimuli include the
modality. In diabetic neuropathy, however, extensive work has evaluation of the entire somatosensory axis, from receptor to
defined how QST can be used in the diagnosis, staging, and cortex, and the assessment of a wide spectrum of sensory fibers
follow-up of patients, with a focus on the application of QST in (Table 11-1). Vibratory stimuli are first detected by Pacini an
clinical trials. 17,27 In several sensory disorders, QST has been corpuscles located in the skin, which in tum activate large
compared with other laboratory measurements of nerve func myelinated fibers (A beta) that carry the impulses to the dorsal
tion, including nerve conduction studies and autonomic testing, column system of the spinal cord. Thermal and painful stimuli
often showing a higher yield of abnormality. are detected by bare nerve endings and are transmitted to the
Most work with QST has concentrated on sensory impair spinoreticulothalamic tracts of the spinal cord by small myeli
ment related to peripheral neuropathies. This bias is a likely out nated (A delta) and/or unmyelinated (C) fibers, depending on
growth of the advances made in neuroradio]ogy, particularly the exact nature of the stimulus. It is important to realize that
magnetic resonance imaging. To date, these modem imaging QST does not effectively localize the site of injury along the so
techniques have shown greater utility and popUlarity in the as matosensory axis.
sessment of central nervous system disorders. 92 Threshold measurements are the most common parameter
used in QST. Although QST instruments are designed to deliver
quantitative data, test results are generated from subjective re
PHYSICAL PROPERTIES OF QST sponses, as the test subject must signal when he or she perceives
the appropriate stimulus. Therefore, methodologic differences
Temperature and vibration are the sensory modalities most or poor adherence to protocols can result in contradictory re
commonly assessed in QST. Other sensory stimuli have been sults. Subject age and height. testing site, the size and pressure
429
430 - PART II BASIC AND ADVANCED TECHNIQUES
TABLE 11·1. Sensory Receptors and Afferent Pathways QST UNITS AND EQUIPMENT
Afferent
Stimulus Receptor FiberType Central Pathways Stimulus intensity can be expressed in two types of units. An
absolute value such as a temperature or micrometer can be used.
Vibration Pacinian corpuscle A-beta Dorsal columns A second system uses "just noticeable differences," (JNDs),
Cold Naked nerve endings A-delta,C Spinothalamic tracts the minimal difference between two stimuli that permits the~ to
Warm Naked nerve endings C Spinothalamic tracts be distinguished, assuming normal sensory function. The full
Cold-pain Naked nerve endings
range of sensation, from threshold to tolerance, can be divided
A-delta,C Spinothalamic tracts
in JNDs. Expressing QST data using JNDs has a physiologic
Heat-pain Naked nerve endings A-delta,C Spinothalamic tracts advantage in that JNDs are small near the sensory threshold and
grow progressively larger at higher stimulus' intensities. 89
Applying JNDs obtained from normal controls to patients with
applied by the stimulator, and subject training all can affect sensory impairment is not a simple process, but, fortunately, has
QST results. Although QST is based on subjective responses, become available with computerized commercial systems.
data collected from cooperative patients have proven to be reli QST instruments can be divided into those that generate spe
able over time. A variety of techniques are in practice to identify cific vibratory or thermal stimuli, and those that deliver electri
poorly cooperative patients including null stimuli 23 and thresh cal impulses at a variety of frequencies to stimulate the different
old variance. 88 classes of sensory fibers. Vibratory stimuli may be produced in
a variety of ways, including vibrating electromagnets and move
ment of a surface mounted to a motorized shaft that undergoes
THE RATIONALE FOR PERFORMING QST vertical displacement proportionate to the current. Thermal
stimuli are uniformly produced using the Peltier principle, first
There are several reasons why QST is of potential value in applied to QST by Kenshalo and Bergen. 56 By alternating the
both research and routine clinical settings. First, routine nerve direction of current through a metal thermocouple (Peltier ele
conduction studies (NCS) are a poor test of small-fiber sensory ment), one can alternatively warm or cool the metal surface. The
function, while small fiber modalities (e.g., thermal and pain amount of current passing through the thermocouple will deter
thresholds) can be quantified with QST. In addition, QST also mine the actual temperature, which is transmitted to a high con
provides a measure of sensory function, something that mayor ductance material that serves as the "active surface." A heat sink
may not correlate with the physiologic properties of the nerve of circulating water sits adjacent to the thermocouple in order to
determined by NCS. As will be described later, there are many improve the efficiency and accuracy of thermal testing. The
instances where QST is more sensitive than NCS in detecting water temperature is maintained by a second thermocouple, al
sensory nerve impairment. Since most peripheral nerve disor lowing for tight control of the active surface's temperature with
ders will eventually impact both small and large sensory fibers, only small adjustments of current. A thermister on the active
QST and NCS can be viewed as complementary evaluations. surface provides continuous feedback to the current generator to
Other advantages are that QST is relatively simple to perform maintain the temperature at the desired level. System software
both in the clinic and in the field and is largely painless. can generate temperatures throughout the physiologic range
Therefore, QST has the potential to serve as a useful screening (O-50°C), alter the duration of the stimulus, and change the
and follow-up procedure in a variety of clinical settings without temperature at rates as high as 6°C per second (Fig. 11-1).
being a burden to test subjects.
ject perceives the specified sensation. Usually several trains are ..,:J
<1l 10
after four trains. 19 E
+'
In response-time exclusive or forced choice testing, the sub til
III
ject is asked whether or not a stimulus of predetermined inten l-
sity is felt. In general, if the subject perceives the first stimulus, S
the next one will be of smaller intensity. A larger stimulus
would follow a negative response. The difference between the
two consecutive stimuli is termed a "step." The sophisticated
equipment and calibration systems required to generate discrete f
+ +
f
.•..f s
+ +
f
steps are now commercially available. 22 There are several differ
ent approaches to response time-exclusive testing. 5 10 15 20
In the method of levels, each step is increased or decreased Test number
by a factor of 2 depending on the subject's prior response. For FIGURE 11-2. Graphic depiction of the 4·2·1 stepping algo
instance, if the response to the first stimulus is negative, the rithm.ln this case, cooling perception was being assessed in the hand.
stimulus is increased two-fold. If the first response is positive, Testing begins on the left side of the figure at JND level 13. Since the
the stimulus is reduced by 50%. The test is completed once the
step size has fallen to a certain level. The threshold is the mean
=
patient perceives the stimulus (5 = success, f failure to perceive), the
intensity of each successive stimulus is reduced 4 JNDs, until a turning
between the last positive and negative response. This type of point occurs at JND level 5.At that point, steps of 2 JNDs are intro
testing can be completed rapidly and, therefore, is suitable for duced. followed by I JND after the next turning point. Five null stimuli
thermal pain testing. 85.86 However, it is prone to error if the sub were inserted at random in the testing sequence and are depicted by
ject is not fully attentive to each stimulus. the zero line on the y-axis. The patient responded inappropriately to
In the staircase method, three steps are predetermined: gross, only the fourth null stimulus. Results were normal in this instance.
medium, and fine. Gross steps are used until the first turn point,
followed by medium steps, and then fine steps. Turn points refer
to the stimulus intensity where the subject either no longer per be performed with two stimulators, one active and one inactive,
ceives or begins to perceive the stimulus. After four negative re instead of using a single stimulator. 3•6
sponses using fine steps, the testing is terminated and a mean is
calculated from the "yes" and "no" responses. 29 Two or more
staircase sequences can be combined randomly in the same train REFERENCE DATA AND OTHER
to eliminate the educated guesswork that may influence subject TESTING ISSUES
responses once they recognize the basic principle of staircase
testing. While control data are available for a variety of testing meth
The 4-2-1 stepping algorithm applies the concept of JNDs. ods, sensory modalities, body sites, and patient age,4.9.14.38.46.55.87.88
Testing begins at the JND level of 13, the midpoint of the 25 it is crucial that these values only be used if the testing condi
JNDs that divide the full range of sensation for the given modal tions are carefully replicated in the QST laboratory.89 The test
ity (Fig. 11-2). Depending on the subject's response to JND ing site, rate of stimulus change, and stimulator size can all
level 13, the next step will increase or decrease four JNDs. After influence the results.4.22 In general, thresholds increase slightly
the first turn point, the step is reduced to two JNDs, and after with age, there are no significant gender or side-to-side differ
the next turn point, to one JND. The test ends after 20 stimuli ences, and response-time inclusive methods produce higher
are delivered, five of which are null. 2! The threshold is calcu threshold values. 89 Data are presented with an upper limit of
lated as a mean of the turn points at the one-JND steps. This normal representing 2 SDs or the 95th percentile. IS Thresholds
method also can be used for heat-pain testing, with the stimulus beyond this level are considered abnormal. For thermal pain
sequentially increasing to the specified point followed by a fall testing, reference data are presented with lower and upper limits
back to adaptation. To prevent skin injury, the ceiling tempera of normal to represent hyperalgesia and hypoesthesia, respec
ture is set at 50°C. tively. QST for thermal thresholds is feasible and reproducible
Forced-choice testing can also be done with dual stimuli, in children as young as age 3 years. 42.46
asking the subject to choose which of two time epochs con Overall, the sensitivity of the various QST methodologies has
tained a stimulus. Since by chance alone, the subject will be not differed significantly in studies. Results from method of
correct 50% of the time, a minimum of three of four correct re limits and forced choice testing are similar in diabetic pa
sponses is generally required before the stimulus intensity is tients. IO•59 There is good agreement between the 4-2-1 stepping
lowered. 15.50 Alternatively, the dual stimulus methodology can protocol and other types of forced-choice testing for vibratory
432 - PART II BASIC AND ADVANCED TECHNIQUES
+>
IJl CLINICAL APPLICATIONS OF QST
(lJ
f-
5 DIABETIC NEUROPATHY
Since it is so common and is frequently the subject of clinical
trials, diabetic neuropathy has been extensively studied with
f s QST. The application of QST in the evaluation of diabetic neu
+
ropathy was recommended in an international conference. I
o 5 10 15 20 Because of the insensitivity of routine nerve conduction studies
Test number to small-fiber impairment, QST of thermal thresholds can be par
ticularly useful.94 Thermal threshold abnormalities may be found
FIGUR£ 11-3. Example of an unreliable test using the 4-2-1
prior to the development of neuropathic symptoms. 30.52,93 QST
stepping algorithm to determine vibratory thresholds in the
remains more sensitive than electrophysiologic studies even in
foot. The patient responded appropriately (f = failure to perceive) to
later stages of diabetic neuropathy when there is significant large
the first two null stimuli depicted by the zero line on the y-axis.
fiber involvement,37,66 Thermal sensitivity was abnormal in 86%
However. the patient claimed to perceive (s = success) the last two
of 142 type-1 diabetics, including approximately 50% of patients
null stimuli. negating the reliability of the results. In this setting. the
who had normal NCS.65 In another study of 280 diabetics, 78%
testing procedure was again reviewed with the subject and the algo
demonstrated abnormalities on warm-cold testing and 39% on
rithm was restarted.
heat-pain. 66 Of the 46 diabetics with normal physical examina
tions, 57% had abnormal thermal testing and only 20% had
and thermal thresholds in healthy subjects and neuropathy pa nerve conduction study abnormalities. In a study of 81 diabetics,
tients.21 In addition, the 4-2-1 stepping method takes only 25% abnormalities on vibratory testing were seen in 88% of patients,
of the time required to perform other forced-choice methods. warm sensation in 78%, and cold in 77%.81 Combining thermal
Experience has shown that method of limits testing is the fastest and vibratory testing, the sensitivity for detecting neuropathy
of the algorithms. While test durations are similar for the differ was over 90% with a specificity of 77-86%. Typically, both ther
ent methodologies in normal subjects,87 forced choice may take mal and vibratory testing are abnormal; however, up to one-third
six times longer than method of limits testing in patients. \0 of patients have isolated thermal abnormalities. 37
Since QST is based on subjective responses, assessing the test Some investigators have proposed that QST serve as one of five
subject's cooperativeness is an important issue. The most evaluations in the diagnosis of diabetic neuropathy, along with
straightforward approach is to include random null stimuli in the scored symptoms, neurologic signs, nerve conduction studies, and
test sequence, something that is automatically done with comput autonomic testing. 20 Abnormalities in two or more of these evalua
erized systems. If subjects respond to null stimuli, the test instruc tions can establish the diagnosis, with NCS or autonomic studies
tions should be reviewed with them again.22 QST data will not be accounting for at least one of the abnormalities. Given the subjec
reliable in those subjects who repeatedly respond to null stimuli tive nature of QST, experts have cautioned against its use as the
(Fig. 11-3).'5.29Yarnitsky and colleagues have proposed the use of sole diagnostic criterion for diabetic neuropathy.25 From a staging
variance measurements of consecutive thermal stimuli in deter standpoint, QST has been found to correlate well with the degree
mining the level of subject cooperation with the testing. 87.88 of small-fiber impairment on examination 39 and the neuropathy
When considering the reliability or reproducibility of QST disability score. 91 In several studies, vibratory thresholds have
results, little data have been published. Reaction time-exclusive demonstrated a close relationship to a variety of measures on
methods, however, are generally favored. Reaction time-inclu motor and sensory NCS.48,57,65 In individual patients, QST thresh
sive methods have demonstrated large inter-session differences olds appear to increase over time, especially in the setting of poor
and problems with repeatability.28.87 Using method of limits test glucose control,41,75 but do not correlate well with the duration of
ing, intersession differences were 150%,28 compared to only 5% diabetes in general. 65 In a study of 405 diabetics followed for 10
using a forced-choice algorithm.50 Still, it is important to realize years or more, toe vibration thresholds were a better predictor of
that no matter what algorithm is employed, consistency of the future diabetic foot complications than standard sensory and reflex
examiner and the testing environment are crucial in generating findings on neurologic examination. I I
reproducible results. The examination room should be quiet and Although most studies have supported a role for QST in the di
free of distraction, instructions should be read at a modest pace, agnosis and staging of diabetic neuropathy, the application of QST
and the same examiner should administer the test in subsequent in the longitudinal assessment of patients enrolled in clinical trials
Chapter II QUANTITATIVE SENSORY TESTING - 433
is likely to be of greatest value. Sensory thresholds have decreased present with distal paresthesias, symmetric stocking-glove sen
in patients who received continuous subcutaneous insulin infu sory loss, and gait ataxia. 40 Vibratory thresholds were checked
sions to maintain tight control of blood glucose levels. 6 In a in 42 post-gastrectomy patients with vitamin B 12 levels less than
placebo-controlled trial, the Nerve Growth Factor Study Group 200 pglml.71 Some patients had deficits that could be explained
found that six months of treatment with recombinant human nerve by myelopathy alone whereas others had evidence of combined
growth factor resulted in a trend toward improvement in various central and peripheral degeneration. Vibratory thresholds
neuropathy measures, including cooling and heat-pain assess recorded from the foot decreased significantly in the 25 patients
ments on QST.2 However, of the QST measures, only the cooling who were compliant with vitamin BI2 injections. Likewise, neu
detection threshold was significantly different when compared to ropathy symptoms improved in this group. Neither vibratory
placebo. In the Rochester Diabetic Neuropathy Study, QST was of thresholds or neuropathic symptoms improved in the remaining
greatest value in measuring neuropathy progression when com patients.
bined with other assessments including examination findings,
NCS, and autonomic testing.25 QST has also been employed in di ALCOHOLIC NEUROPATHY
abetic neuropathy treatment trials of gamma-linoleic acid54 and
aldose reductase inhibitors. 31 Unfortunately, vibratory and thermal The neuropathy associated with longstanding alcohol abuse
testing was not found to be a sensitive indicator of improvement in involves both large and small sensory fibers, supporting a role
26 insulin-dependent diabetes patients who received combined for both vibratory and thermal QST in this clinical setting.92 In
pancreas and kidney transplantation for end-stage nephropathy. 100 men with 11-13 years of heavy alcohol consumption, foot
QST did not mirror the improvement seen in clinical and electro vibratory thresholds were significantly higher than in 52 control
physiological parameters in six patients with functioning trans subjectsJ4 Higher thresholds were seen in the alcoholic group,
plants at a mean postoperative interval of 41 months. 79 whether or not they had neuropathic symptoms, suggesting that
QST could be helpful in detecting subclinical neuropathy.
UREMIC NEUROPATHY Thermal testing was performed on a group of 50 patients with
chronic alcohol abuse of at least 7 years. Cold thresholds were
Uremic neuropathy is an axonal sensorimotor polyneuropa increased in 62%, warm thresholds in 24%, and heat-pain in
thy that predominantly affects large myelinated fibers. As a 22%.43 Complete hypoesthesia to heat-pain or cold-pain, and a
result, vibratory thresholds have been the focus of QST in this paradoxical sensation of warmth to cold stimuli were seen in
form of neuropathy. Vibratory thresholds were higher in 97 pa about 10% of patients each.
tients with chronic renal failure compared to a large control
group.67 Vibratory abnormalities correlated with the degree of HIV-RELATED NEUROPATHY
renal impairment in men but not in women. Overall, the vibra
tory testing results reflected the clinical severity of the neuropa QST has been applied in HIV-infected patients, primarily to
thy. NCS were actually more sensitive in detecting neuropathy, characterize the distal, symmetric, and painful neuropathy that
with 82% of patients showing abnormalities compared to only develops in as many as one-third of patients with advanced dis
32% on QST. In a study of 64 nondiabetic patients with chronic ease62.72.82 and to assess neurotoxicity from antiviral agents.
renal failure, clinical signs of neuropathy were present in Thermal testing, especially for warmth perception, was more
65%.60,78 NCS were again more sensitive than QST in detecting sensitive than NCS in detecting sensory nerve impairment in
neuropathy, with 90% of patients demonstrating electrophysio HIV patients. 52 Thermal thresholds were abnormal in 50% of
logic abnormalities compared to 36% on vibratory testing and symptomatic patients with normal NCS and in 30% of patients
30% on thermal testing. However, vibratory thresholds showed without symptoms. In another study of 179 HIV-seropositive
the closest correlation with clinical findings. 60 In another study, patients, vibratory thresholds had a similar rate of abnormality
vibratory testing was found to be more sensitive than using a as NCS.36 As expected, QST abnormalities were more common
tuning fork in detecting large-fiber sensory impairment in both in the 28 subjects who had progressed to AIDS-related complex
uremic and alcoholic patients. 44 Several studies have docu (ARC) or AIDS, with elevated vibratory thresholds found in
mented stabilization or improvement of vibration thresholds in 36% of these patients. Vibratory thresholds were more sensitive
uremic patients receiving hemodialysis. 12,77 than NCS in screening for subclinical neuropathy related to the
While thermal testing has largely been found to have less antiviral agent 2',3'-dideoxycytidine (ddC), but once patients
value than vibratory testing in uremic neuropathy, in one study were symptomatic, both NCS and vibratory thresholds were
42% of patients with end-stage renal failure developed a sensa abnormal in the large majority of patients. s Vibratory threshold
tion of warmth or heat to cold stimuli delivered to the feet. 90 abnormalities were a rare finding in patients receiving zidovu
This paradoxical response is seen in less than 10% of normals. dine. 8 However, thermal thresholds, which may be a more ap
The paradoxical response was the only QST abnormality in propriate test for the painful, hyperesthetic symptoms caused by
1 ) % of patients and correlated with serum creatinine levels. The this drug, were not performed.
authors suggested this response could serve as an indicator of
worsening renal failure or insufficient hemodialysis. Heat-pain CRYPTOGENIC SENSORY POLYNEUROPATHY (CSPN)
thresholds are not particularly sensitive in the detection of
uremic neuropathy, being abnormal in less than 10% of patients Chronic sensory or sensorimotor polyneuropathy of unknown
with clinically-evident neuropathy.90 cause is a common disorder that tends to present in the sixth to
seventh decade of Iife. s3 These patients represent anywhere
VITAMIN BI2 DEFICIENCY STATES from 10% to one-third of all polyneuropathies seen in referral
centers.16,58.63,68.70 Approximately 70-80% of these neuropathies
Vitamin B12 deficiency may lead to both central and periph are painfu)33.34,68,S4 and when small-fiber involvement predomi
eral nerve dysfunction. Patients with this neuropathy typically nates, electrophysiologic testing may be normal in nearly 50%
434 - PART II BASIC AND ADVANCED TECHNIQUES
of patients. 33 Therefore, QST, especially thermal testing, could mediate warmth-are less affected by compression than small
serve as a valuable laboratory assessment in these patients. unmyelinated axons that sub serve cold stimuli.
In our experience, QST for cold and vibration detection
thresholds has a slightly higher yield than NCS in the detection Illustrative Case
of abnormalities in CSPN.84 Sensory NCS were abnormal in History. A 46-year-old man presented with a 20-month his
77% of our patients, compared to QST abnormalities in 85%.84 tory of uncomfortable sensations in his feet that began duriQg a
This figure is similar to the 88% frequency of QST abnormali hospitalization for acute pancreatitis. He received total par
ties in a report of patients with idiopathic painful sensory neu enteral nutrition for three months with resolution of the foot
ropathy.69 In our CSPN population, both cold and vibration symptoms. However, several months later, the burning, stinging
thresholds were abnormal in two-thirds of patients. 84 Abnormal and shock-like sensations returned, spreading from his toes up
cold but normal vibration thresholds were seen in 9 patients, to the heels. Similar dysesthesias and numbness also developed
but abnormal vibration and normal cold thresholds in only two, in the fingertips of both hands. He denied weakness, only re
perhaps reflecting the greater degree of small-fiber impairment porting that his feet felt "tired" by the end of the day. His bowel
in these patients. In approximately 10% of patients with abnor and bladder function were unchanged. Medical history was no
mal QST, there was no evidence of neuropathy on NCS. table for a single episode of pancreatitis 2 years earlier that re
Studies of idiopathic small-fiber neuropathies in the setting of mained unexplained. He underwent a hernia repair 12 years
normal electrophysiologic testing have demonstrated thermal earlier and had pneumonia as a child. There was no history of
threshold abnormalities in anywhere from 57%47 to 100% of diabetes or ethanol abuse. He was not on any medications.
patients. 51 In another study describing 30 patients with painful, Physical Examination. On neurologic examination, cra
burning feet, only one had abnormal NCS.73 On the other hand, nial nerves were intact. Muscle bulk and tone were normal,
either warming or cooling thresholds were elevated in 12 and strength was full in both the upper and lower limbs, in
(40%) of these patients. cluding toe extensors and flexors. Deep tendon reflexes were
grade 2 except for absent responses at both ankles. Plantar re
OTHER APPLICATIONS sponses were flexor bilaterally. On sensory testing, light
touch, temperature, and pinprick were reduced in both feet up
QST has been evaluated in a variety of other neuropathic to the ankle level. Timed vibration was slightly reduced in the
states, including carpal tunnel syndrome and lumbosacral toes. Position sense was intact. His gait was normal without a
radiculopathies. Since these disorders are relatively common, Romberg sign.
QST has potential attractiveness as a mass screening tool in Laboratory Data. Laboratory testing was unremarkable, in
these clinical scenarios.92 Unfortunately, the sensitivity32.35.64 cluding 2-hour glucose tolerance testing, thyroid function, vita
and specificity of QST7.49 in carpal tunnel syndrome has been min B 12 , serum protein and immunofixation electrophoresis,
poor in several studies. For instance, thresholds in the fifth ESR, ANA, RF, SSA, SSB, HIV, and syphilis serologies. Anti
finger are often abnormal in patients with carpal tunnel syn Hu antibody testing was negative.
drome, raising serious questions about the utility of QST in this Nerve Conduction Studies. Nerve conduction studies were
mononeuropathy.1,49 Overall, there is little evidence to support performed in the right upper and lower limbs and were normal.
the use of QST in the diagnosis of carpal tunnel syndrome. It
DSL SAmp DML MAmp NCV Fwave
has a lower sensitivity than standard electrophysiologic testing (m/s) (ms)
Nerve (ms) (J!V) (ms) (mV)
and often fails to demonstrate a pattern consistent with
R median 3.5 44.3 3.9 6.9 56.4 28.3
mononeuropathy.
R ulnar 3.0 31.3 3.1 8.4 58.5 30.8
The role of QST in evaluation of lumbosacral radiculopathy
R peroneal 3.8 8.6 44.4 50.5
has not been established. Thermal thresholds for warmth were
R tibial 4.4 9.9 43.6 52.7
increased in dermatomes ipsilateral to the root compression
R sural 3.8 9.1
while heat-pain thresholds were normal ipsilaterally but surpris
ingly decreased in contralateral dermatomes. 76 The authors pro DSL, distal sensory latency; S Amp, sensory amplitude, DML,
posed that this discrepancy is related to different responses of distal motor latency; M Amp, motor amplitude; NCV, nerve
fiber types to chronic root compression. Compression of fibers conduction velocity; ms, milliseconds; 11V, microvolts; mis,
mediating warmth would manifest only ipsilateral findings. meters per second. Motor and sensory amplitudes are measured
Nociceptive fiber compression, however, would produce bilat baseline-to-peak. Sensory latencies are measured to peak, and
eral changes. The decreased heat-pain threshold on the con motor latencies are measured to initial negative onset.
tralateral side could be related to a loss of inhibition resulting
from large fiber compression. On the ipsilateral side, compres Needle Electromyography. A needle electromyographic in
sion of both large fibers and nociceptive small fibers would ef vestigation of distal muscles in the right upper and lower limbs
fectively produce a sensory equilibrium, with no significant was normal, except for rare fasciculation potentials in the ab
change in the heat-pain threshold. In another study, warm ductor hallucis.
thresholds were significantly higher on the symptomatic side
Rest MUAP Recruit-
compared to the asymptomatic limb in 40 patients with L5 or
Muscle activity Morphology ment
SI radiculopathies. 95 Cold thresholds were also significantly
R gastrocnemius Silent Normal Normal
higher on the symptomatic side in those patients with surgically
R tibialis anterior Silent Normal Normal
confirmed disk herniation. Since warm thresholds were affected
R abductor hallucis Silent Normal Normal
to a greater degree than cold thresholds, the authors hypothe
R first doral interosseous Silent Normal Normal
sized that inflammation plays a greater role than compression
in the generation of sciatic pain. This conclusion is based on Quantitative Sensory Testing. QST was performed on both
prior observations that unmyelinated axons-such as those that hands and both feet using the 4-2-1 stepping algorithm (Fig. ll-4).
Chapter II QUANTITATIVE SENSORYTESTlNG - 435
,
25 ,--------,--------r--------.--------~ over the next year. No further diagnostic work-up is recom
sti/ftull _ mended at this time. Treatment is largely symptomatic (e.g,
measured threshold -
null stiMuli + antiepileptic medications, tricyclic antidepressants, tramadol).
26
Comments
s This case illustrates the clinical utility of QST. The patient's
history and examination are suggestive of a predominantly small
...,'"z 15 fiber sensory neuropathy. The motor and sensory nerve conduc
tion studies as well as electromyography were completely
normal. As noted previously, QST is more sensitive in evaluating
individuals with small fiber neuropathies than routine nerve con
16
duction studies, which mainly assess large myelinated fibers. In
this case, the abnonnal QST was helpful in confirming the clini
cal impression that the patient had a small-fiber neuropathy.
5 Despite an extensive laboratory work-up for causes of small-fiber
neuropathy, no etiology was detennined and he was diagnosed
with cryptogenic or idiopathic sensory polyneuropathy (see
f f Chapter 23). The patient's symptoms have remained relatively
o . +.
stable and have not interfered with his daily activities. Therefore,
a 5 10 15 20 he opted not to start pharmacotherapy for symptom relief.
Test number
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Chapter 12
Intraoperative
Neurophysiologic Monitoring
John C. King, M.D.
Jaime R. L6pez, M.D.
Tod B. Sloan, M.D., Ph.D.
neurophysiologic monitoring for high-risk procedures has The function of those nervous system pathways listed in Table
become, or is emerging as, the standard of care. In 1995, 88% 12-1 should ideally be monitored continuously during the surgi
of surgeons performing scoliosis procedures routinely used cal procedure, or at least during that portion of the procedure that
intraoperative electrophysiologic monitoring. 288 Owing to in places the nervous system at greatest risk. This may involve real
creasing demand, it is important for competent clinical neuro time monitoring, such as over a loudspeaker or on a continuous
physiologists to be able to offer their expertise to help establish video display, or often by means of a periodically sampled, aver
or directly provide such services. No one is more specifically aged, and video-displayed response. Periodicity is necessary to
trained, capable of understanding the procedures. able to inter average many dozens to hundreds of stimulations to minimize
pret electrophysiologic monitoring results, and appreciative of the random environmental electrical noise that contaminates and
their limitations and potential pitfalls than electrodiagnostic obscures the eJectrophysiologic signal of interest. Sources of the
medicine consultants. electrical noise commonly encountered in the operative suite and
steps to reduce these effects are listed in Tables 12-3 to 12-6. In
NEUROPHYSIOLOGIC SYSTEMS order to permit more rapid deficit onset detection, the epochs of
MONITORED INTRAOPERATIVELY sufficient numbers of averages to produce a reliable response are
continuously repeated during the entire or key portions of the
Many types of neurophysiologic monitoring systems and surgery. Detailed reviews exist for intraoperative monitoring
techniques are available (Table 12-1). In addition to direct elec techniques, frequency of use, and their clinical utility, which are
trical stimulation of these neural pathways, other stimuli can be recommended for additional reading. 8,9,11,21,44,223,281,288,336,344
used to provoke recordable responses (Table 12-2). Those neuro
physiologic systems commonly monitored have been published
with at least case series results demonstrating effectiveness or Table 12-3. Increase in Amount of Artifact
usefulness. 1,5,13,24,27,54,80,94,102.106.1 14.132.146.162,163.165.180,201,221,227,228,233.264, Problem/Cause Detection Action
265.288,312,330,337.395-397.423,425
High-impedance Check electrode impedance Switch to duplicate
electrode electrodes
Increased EMG View input signal. check Patient may be
Table 12·2. Some Stimuli That Can be Used to
anesthetic level "light"; request in
Elicit Evoked Potentials
creased anesthesia
Visual Auditory or use NM block;
Diffuse flash Clicks increase number
Checkerboard reversal Brief tones of stimuli
Moving gratings or bars Syllables Electrocautery High-amplitude noise caus- Wait. resume when
Flickering Words ing amplifier block cautery stops and
Partial field stimuli Musical chords (saturation) amplifiers recover
Other Rhythmic. high-amplitude Turn off one source
Somatosensory Other
equipment noise.View input to of noise at a time
Median nerve Brief joint movements
determine frequency while looking at
Digital nerve Respirator air bursts
Posterior tibial nerve Olfaction
Trigeminal nerve branches Temperature = =
EMG electromyography; NM neuromuscular.
Skin dermatomes From Erwin CWO Erwin AC:The use of brain stem auditory evoked potentials in
Complex tasks
intraoperative monitoring. In Russell GB. Rodichok LD (eds): Primer of
From Nuwer MR (ed): Evoked Potential Monitoring in the Operating Room. Intraoperative Monitoring. Boston. Butterworth-Heinemann. 1995. pp 135-158.
Table 12-4. Most Common Sources of Artifacts in the (SEPs). The distal nerve (usually a compound nerve) is stimu
Operating Room lated and the cortical response monitored. This was one of the
I. The Bovie coagulator first and most common techniques used in an attempt to monitor
2. Heating devices (blood warmer, heating blanket) spinal cord function during scoliosis surgery.37.69.122a,288,290,344.375
3. Operating microscopes Intraoperative SEP monitoring results for scoliosis surgery have
4. X-ray view boxes
been studied by the Scoliosis Research Society in a large series
of 51 ,263 patients,288,290 with its sensitivity, specificity and posi
5. X-ray devices, such as a C-arm
tive as well as negative predictive values demonstrated (Table
6. The operating table itself 12-7). It is also the most common intraoperative neurophysio
7. Metal placed on or near the patient, such as spinal logic monitoring technique performed, especially during spine
instrumentation or metal head holders surgeries or direct spinal cord neurosurgical procedures that
From Rodichok LD. Schwentker MC: Special problems in the operating room. may threaten the spinal cord's function. I (r.18.22.49.66,68.73.89.95,96,123.13S.
In Russell GB, Rodichok LD (eds): Primer of Intraoperative Monitoring. Boston, 195.196,198,199.232.243.247,251,257.264.266.274.282.285.289.290.321,326.344.356.374.375.403,413.
Butterworth-Heinemann, 1995. pp 241-244. with permission. 416,430.437,439
For some spine surgeries, monitoring mUltiple threatened
SOMATOSENSORY EVOKED POTENTIALS nerve roots is also desirable, for which dermatomal somato
sensory evoked potentials (DSEPs) have been attempted. 58•406•408
Peripheral nerve through cortical sensory pathways can be A 2% incidence of nerve root deficits has been found after
monitored by means of somatosensory evoked potentials scoliosis surgery, which had not been predicted by SEP
Table 11-5. Artifactual Shift of Latency or Loss of Response During SEP/BAEP Monitoring
Problem/Cause Detection Action
Stimulus Input Defects
Cable/electrodes faulty Sudden loss of response. including first Reseal connections, verify correct placement, or
peaks and peripheral responses; change to backup cables/electrodes; Replace
verify connections/positioning. use defective cables/electrodes for next time
back up cabling/electrodes
Stimulator/click
Suspect during surgery. connect new Increase stimulus intensity; if no improvement,
transducer faulty
stimulatorltransducer to confirm connect new stimulator after testing with backup
cables/electrodes
Stimulation electrodes or Suspect during surgery. confirm by Increase stimulus intensity. improve placement and
transducer dislodged inspecting placement and securing techniques next time
Conductive loss (BAEP) Suspect during surgery, confirm by Increase stimulus intensity, improve sealing of ear
(fluid in ear canal) inspecting placement canal (adhesive dressing, etc.)
Recording Pickup Defects
Cable/electrode breakage Sudden loss of EP response with pre Check electrodes placement, use backup electrodesl
or dislodgement servation of peripheral responses cables if functional. while checking cable/electrode
(that verify input) connections. If no EP response with back ups,
notify surgeon. If during high risk maneuvers.
notify surgeon before checking back up systems.
Excessive noise Averaged response much more ragged, Increase stimulus intensity, reposition dislodged
peaks less discernible, reproducibility electrodes. verify cabling connections are secure
diminished and initial peripheral input detectable or see
above
Excessive high-frequency Check filter settings Return filter to baseline settings or decrease high
noise frequency cutoff
Excessive baseline drift Check filter settings Return filter to baseline settings or increase low
frequency cutoff
Noise masking Sudden high amplitude noise apparent Increase stimulus intensity. pause averager during
in input and averaged response drilling. and/or clear averaged response and
(drilling. cautery. etc.) restart
Slow drift over minutes Compare with previous and baseline Check with anesthesiologist for concurrent
in amplitudes or latency averages anesthetic or body temperature changes, if none
sufficient to account for changes, and at alert
thresholds, notify surgeon (possible vascular or
mild traction
From Erwin cwo Erwin AC: The use of brain stem auditory evoked potentials in intraoperative monitoring. In Russell GB. Rodichok LD (eds): Primer of
Intraoperative Monitoring. Boston. Butterworth-Heinemann. 1995, pp 135-158. with permission.
442 - PART II BASIC AND ADVANCED TECHNIQUES
Table 12-6. Procedures to Help Decrease reliable technique than the usually employed peripheral mixed
Intraoperative Artifacts nerve stimulation SEP in detecting root injuries. 151 ,154,169,298
Remove grease and abrade skin before applying disc scalp electrodes. However, if the selective root is directly stimulated, the result
Glue electrodes down with collodion. ing SEP may reliably indicate that particular root's compro
If electrodes are on overnight, re-gel and abrade scalp again in the mise. 228 ,36O Peripheral nerves at risk can also be monitored by
operating room. means of SEP, such as may occur in various orthopedic prQce
dures, e.g., total hip arthroplasty and fracture fixa
Keep electrode impedances at approximately 2000 ohms.
tions. I13 ,182,237,381,384 In addition to direct nerve compromise by
Use the shortest electrode wires that can be securely fastened out of
physical means, SEP has been used to monitor vascular proce
the way.
dures that may hemodynamically compromise spinal cord func
Use short interelectrode distances between pairs of recording tion, such as spinal cord arteriovenous malformations,
electrodes.
cardiopulmonary bypass procedures, or thoracic aortic
Braid the recording electrode wires together. aneurysm resections. 23,60,65-67,72.83,86,1 09,126,176,195,198,200,205-207,209,220,
Have back-up stimulus and recording electrodes available and already 234,244,253,280,296,340,347,353,383,426,433
in place on the patient. Owing to the anesthetic blunting effects on the cortical re
Keep recording and stimulating wires and cords as far as practical sponse, others have additionally monitored the spinal cord tracts
away from each other. directly, usually by means of peripheral nerve stimulation and
Do not cross cables or wires over other cables, especially power recording a near-field spinal cord evoked potential (SCEP)
cables. through interspinous ligament, epidural, or subdural elec
Do not kick, jar, or sway wires (secure or tape out of the surgeons trodes. 10,108,130,163,228,272,328,421-423,439 Advantages of SCEP record
and anesthetists' way). ings include less deterioration from anesthetics, less
Keep the low filter above I Hz whenever possible. deterioration at higher stimulation rates, permitting up to 3D-Hz
Unplug unused equipment (not just off). stimulation as opposed to 5 Hz or less usually required to opti
mize cortical SEP responses. 96,283,285,355,37I,395,396,409 Higher stimu
Avoid appliances with 2-pronged power plugs (ungrounded).
lation frequencies permit more rapid averaging of the evoked
Stop averaging whenever amplifiers are saturated (e.g., during
potential, obtaining results in epochs as short as 3-4 seconds,
electrocautery).
compared with 1-2 minute epochs required for cortical SEPS.285
Adjust sensitivity so that some normal trials result in artifact
A disadvantage of direct spinal cord recordings is the use of
rejection activation.
more invasive electrodes, usually being required in the opera
Use enough neuromuscular junction blocking agents (if only SEP and tive field or epidural space (Table 12-8), Direct spinal cord stim
not EMG or MEPs recorded). ulation is often possible intraoperatively and has been used with
Delay recording until several ms after the stimulus (to avoid inter cortical (SEP) recordings or recordings made directly from the
ference by the stimulus artifact). spinal cord (SCEP).262,272 The recording site for SCEP is usually
Verify adequate stimulus input by a peripheral pickup to verify stimuli more cephalad to the surgical area with cord stimulation dis
are being applied. tally. Also, recordings from distal muscles or nerves can be used
(From Nuwer MR (ed): Evoked Potential Monitoring in the Operating Room. with direct spinal cord stimulation. 2,106,152,196,23I,27I,297,299,
New York, Raven Press, 1986, p 39, with permission.) 312,397,395,396,400 Intraoperative SEP continues to be useful and
one of the most frequently used techniques for monitoring
many types of surgical procedures. SEP intraoperative mon
monitoring. 136 DSEP studies result in smaller cortical evoked itoring provides early warning of impending harm to the
responses and have not had the reproducibility and reliability
found with peripheral mixed nerve SEPS.406,408 Fortunately, con
tinuous selective electromyography has been found to be a more Table 12-8. Comparison of Cortical SEP Versus SCEP
Recording Techniques
Spinal Cord
Table 12-7. SEP Monitoring in Scoliosis Cortical SEP Evoked Potential
Sensitivity 92% Minimum time to 1-2 minutes 10-30 seconds. epidural
417*1451** produce each EP 1-2 minutes.ligamental
Specificity 98.8% Forane 0.5% Usually gone Usually preserved
50,207t /50,78 I ttt Can monitor caudal Yes Yes
Positive predictive value 42% to surgery too
41r1991* Begin monitoring At or before After wound opening
Negative predictive value 99.3% induction
50,207t /50.24 Itt Discontinue After awakening Upon wound closing
Key: * Patients with new permanent neurologic deficits (NPND) as pre monitoring
dicted by monitoring
Total number of patients with NPND Wires Hidden In surgical field
t = Patients without NPND with none predicted by monitoring Risk of damage Negligible Epidural-small
tt = Total number of patients with no monitoring prediction of deficits Ligamental-negligible
ttt = Total number of patients without NPND
* = Total number of patients with monitoring prediction of deficits From Nuwer MR: Monitoring spinal cord surgery with cortical somatosensory
From Nuwer MR: Spinal cord monitoring. Muscle Nerve 1999;22: 1620-1630. evoked potentials. In Desmedt JE (ed): Neuromonitoring in Surgery.
with permiSSion. Amsterdam. Elsevier. 1989. pp 158-164. with permission.
Chapter 12 INTRAOPERATIVE NEUROPHYSIOLOGIC MONITORING - 443
From Lee EK, Seyal M: Generators of short latency human somatosensory-evoked potentials recorded over the spine and scalp. J Clin Neurophysiol
sensory function of the spinal cord and helps to guide surgi BRAIN STEM AUDITORY EVOKED POTENTIALS
cal progress. 8 ,17,18,3I,94,264,273,274,290,425 The SEP components that
can be monitored and their field distributions are shown in The special sensory tracts involved in hearing can be moni
Table 12-9. 211 The cortical SEP waveform peaks more com tored by brainstem auditory evoked potentials (BAEPs).53,74,103,
monly monitored are the P371N45 potentials for tibial nerve 124,139,140,239,245,295,399,414,430 These are called "brain stem" because
stimulation, and the N20/P22 potentials for median nerve much of the brain stem is involved in the transmission of audi
stimulation. tory input before it is relayed to the auditory cortex, The BAEP
consists of many peaks that represent various transmission and
synaptic brain stem centers. The most important waveform
Table 12-10. Brain Stem Auditory Evoked Potentials peaks to monitor are the first (representing the auditory nerve
Field Distributions portion of the VIII cranial nerve) and the fifth (representing the
10-20 final pathway through the brain stem) (Table 12-10).97
Recording
Cz-Ai Cz-Ac ELECTROMYOGRAPHY
Wave I Upgoing. later than 1.3 ms Virtually absent
Wave II Usually present but absent If present, similar amplitude
Electromyography can evaluate irritation to peripheral motor
in some normal individuals to Cz-Ai -0.1 ms later
nerves in real time and can alert the surgeon to inadvertent trac
tion on a nerve.45,1l6,13l.140,151,170,185a.298,328. By use of multi-trace
(not an obligate wave)
real-time recordings, many different cranial or peripheral nerves
Wave III Present in normals Lower amplitude (sometimes or nerve roots can be monitored simultaneously. However, there
virtually absent). -0.0 I ms are multiple intraoperative sources of motor nerve irritation,
earlier than Ai which can include such benign events as saline nerve lavage,
Wave IV Not obligate If present, -0.0 I ms later which nevertheless create the spontaneous 'motor discharges
Wave V Obligate, largest of waves, Larger, more separated from charges are irregular rapid motor unit firings that can easily be
than Ai in the operative field, and thus multiple muscles must be moni
tored simultaneously. Unfortunately, complete lysis of a nerve
From Erwin Cw. Erwin AC:The use of brain stem auditory evoked potentials in
intraoperative monitoring. In Russell GB, Rodichok LD (eds): Primer of can occur without necessarily generating neurotonic discharges.
Intraoperative Monitoring. Boston, Butterworth-Heinemann, 1995, pp 135-158. Additionally, detection of such discharges is obscured during
with permiSSion. the electrically noisy event of electrocautery.141
444 - PART II BASIC AND ADVANCED TECHNIQUES
-
tion.312 A study of tethered cord surgery found that a response
..... recorded with a I-lOrna stimulation meant the stimulator was
directly on the nerve, whereas 11-25 ma implied near the nerve
.......
58W
but with intervening tissue, and greater than 25 rna indicated the
nerve was distant to the stimulation site. 312
Figure '2-', Neurotonic discharges. A 52-year-old female under MOTOR EVOKED POTENTIALS
going aT 12-L2 intraspinal tumor resection. The neurotonic discharges
Motor evoked potentials (MEPs) assess the motor systems
in traces 2.3,6, and 7 are seen during the time of resection.
from the motor cortex to the anterior horn cell and then by way
Recordings were done using intramuscular hook-wire electrodes of the peripheral nerves to the muscle proper. 43 ,47.70.92.127,144,
placed in the following muscles: 160,166.177.203,204.217,243,263,267,271.297,308,324,341.440,441 Avoiding paralysis is
Trace I: Left vastus lateralis Trace 5: Right vastus lateralis
Trace 2: Left tibialis anterior Trace 6: Right tibialis anterior a major intraoperative concern, and monitoring these pathways
Trace 3: Left medial Trace 7: Right medial should theoretically permit better detection of intraoperative
gastrocnemius gastrocnemius motor function 10ss.290 Animal studies suggest greater sensitiv
Trace 4: Left anal sphincter Trace 8: Right anal sphincter ity to spinal cord traction may occur with MEPs than SEPs, with
a change in the MEP at 5-10% distraction, but no change in the
NERVE CONDUCTION STUDIES SEP until 15% distraction. 335 The advantages and disadvantages
of MEP versus SEP monitoring are further discussed in Table
Nerve conduction studies (NCSs) help to quantify nerve in 12-11. Unfortunately, electrical transdermal cortical motor
tegrity. Whereas real-time EMG may detect even small irrita stimulation is painful, though not a significant obstacle in the
tions, a decline in the nerve conduction response is somewhat anesthetized patient. 42.43,47.146,172.177.335.379.410 Less uncomfortable
more proportional to the severity of compromise of the nerve magnetic stimulation systems have been developed. 127,144.172,m,
being tested. 1 13. Traction results in rapid declines within 1-2 335.341.398 However, both these techniques remain experimental in
minutes, whereas partial vascular compromise results in slowly the United States. 335 Both types of transcranial stimulation place
progressive potential declines over longer times, approaching the patient at increased risk of a seizure; however, during anesthe
10-20 minutes, although if the vasculature is completely sia this is rarely a problem. Several papers addressing the safety
oblated, immediate decline in neural function will result. If such and theoretical concerns about transcranial cortical stimulation
neural compromise persists for greater than 30 minutes, irre have been favorable. 3,26.59 Monitoring of motor pathways by means
versible neurologic insults may ensue. 65•66,I28.285 If a tourniquet is of MEPs, NCSs, or EMG requires that the motor system is not
used to exsanguinate an operative field, an additional 20 min subject to total motor blockade, and the anesthetic requirements to
utes for nerve function recovery following tourniquet release accomplish this are discussed below in Anesthesia Considerations.
may be required, making this a relative contraindication to mon
itoring. 25 NeSs can be used to evaluate improvements across ELECTROENCEPHALOGRAPHY
decompressed sites, which can help guide a surgeon as to the
adequacy of nerve decompression, as well as to monitor for Electroencephalography (EEG) is used to monitor the vascu
worsening of function. The NeS can also help identify neural lar supply to the cortex during neurosurgical procedures such as
Table 12·11. Comparison of Intraoperative SEP versus MEP Spinal Cord Monitoring Techniques
Modality Advantages Disadvantages
Somatosensory-evoked Readily available sites for stimulating and recording Requires experienced personnel and dedicated equipment
potentials (SEPs) Subcortical recordings allow use of potent inhaled agents Cortical recordings attenuated by potent inhaled agents
Generally detects spinal cord injuries May not detect isolated motor injuries
Motor-evoked Depending on stimulating and recording sites, does not May not be readily or universally available. Experienced
potentials (MEPs) require significandy more equipment than SEPs alone monitoring team requested
May be more sensitive to impending injury than SEPs Potent agents and muscle relaxants restricted in certain
Allows monitoring in selected cases with absent SEPs circumstances
Combined with SEPs, provides "whole cord" monitoring Movement during stimulation may interfere with surgery
From Adams DC. Emerson RG: Intraoperative spinal cord monitoring. Curr Opin Anaesthesiol 1996;9:372, with permission.
Chapter 12 INTRAOPERATIVE NEUROPHYSIOLOGIC MONITORING - 445
carotid endarterectomy or aneurysm clipping.4.55 .56.200.250.268.304.310. Surface electrodes may be used such as gold cup EEG elec
319.320.322.332.388.407.415,438 A window exists as cortical blood flow is trodes, bar electrodes, flat plate electrodes or standard NCS ring
compromised in which cortical electroencephalographic activ electrodes, subdermal EEG electrodes, or highly specialized
ity is diminished and then abolished prior to reaching the criti custom-made probe electrodes. However, many of these custom
cal level of blood flow and oxygen supply that leads to electrodes are becoming more generally available through elec
irreversible cell death. 352•386,387,428 The loss of EEG activity trode companies and are autoclavable for re-use. This includes
allows the surgeon to take corrective actions to improve cortical electrode forceps that can touch or hold a structure. These for
blood flow and minimize permanent neurologic ischemic post ceps are designed for stimulation, with each prong being the
operative deficits. pole of a stimulator. They can also be configured to serve as
pickup electrodes. When not being used as a stimulator or as
VISUAL EVOKED POTENTIALS sensing electrodes, these forceps can be used to dissect as with
any forceps. Often, custom hooks are used as stimulation and
Visual evoked potentials (VEPs) monitor the visual pathways pickup electrodes. Though usually spaced closer than the ideal
from the retina to the occipital visual cortex.99.270.323.382.431.435 4 em for recording, in order to better accommodate intraopera
VEPs are used infrequently, owing to both technical difficulties tive field limitations, these active and reference electrodes can
and risks. Usually, other methods can cover the same general reliably detect a response and a decrement in that response.405
operative areas. 284 Reports of intraoperative YEP monitoring Monopolar recordings with a distant reference have also been
have generally been unfavorable. 99.382 used effectively when operative fields are restricted. 68 When
used as stimulating electrodes, the shock artifact can be rather
EQUIPMENT REQUIREMENTS large if both the stimulation and pickup are occurring in the
same relatively small operative field. To minimize the shock ar
Multiple neurologic systems can be monitored by the many tifact, sometimes a monopolar cathodal stimulating electrode (a
techniques described (see Table 12-1). Certain surgical proce single hook or probe) is used with a distant anode, usually a sur
dures will require concurrent monitoring of several different face electrode. This also permits a more focal stimulation with
systems. Some techniques require electrical or other (see Table less likelihood of cross-stimulation to adjacent nerves. The spe
12-2) stimulation of a nervous structure with recording of sub cific placement and connection of these electrodes, called the
sequent time-locked responses. These responses are often of montage, are discussed with each technique.
small amplitude compared with the operating room's electri The operating environment is both electrically and mechani
cally noisy environment, requiring the averaging of many stim cally hostile. Electrodes initially secured for continuous moni
ulations to obtain a reliable response. Sources of electrical noise toring use may become dislodged during a procedure. Backup
in the operating room include ventilators, blood warmers, elec electrodes and equipment are essential to minimize technical
trocautery, and other devices used to monitor the depth of anes failure. Constant vigilance for technical failures is essential to
thesia and motor blockade (see Table 12-4).327 Other techniques prevent unnecessary alarm or delays in the surgical procedure.
require real-time display by auditory loudspeaker or continuous Protocols to minimize electrical interference and decrease intra
video trace display, and some channels may require different operative artifacts are listed in Tables 12-3, 12-5 and 12_6. 284•286
sweep speeds as well as different sensitivity settings. Fre
quently, multimodal monitoring, combining multiple displays GENERAL RESULTS AND EFFICACY
of real-time and averaged signals, is desired in order to evaluate
all or as many systems as possible that are at risk. Since some Many of the above-described techniques are sensitive but not
techniques require averaging of the response to stimulation and particularly specific. False-positive results (loss of the desired
others are real-time displays, sophisticated equipment may be response without actual pathology to the monitored system)
required that allows differing time bases (sweep speeds) and occur much more commonly (approximately 5% rate, with
triggering for each trace to be displayed concurrently. Also, the about half of these accountable to transient technical failures)
same or similar cortical structures may need to be stimulated al than true-positives (which for scoliosis surgery SEP monitoring
ternately and each side's response averaged to check both sides occurs at about a 0.4% rate).44.96.l02.290 Even a transient loss of
of the neuraxis such as when performing bilateral alternating signals places patients at greater risk of permanent deficits,
tibial or peroneal nerve stimulation. 290 Such ability to interlace though the highest risks are for those with initially easily ob
stimulations, averages, and real-time response recordings is tainable responses that gradually disappear, having about a 50%
available in the high-end electrophysiologic instrumentation risk of permanent sequelae.l02.105 Some of the "false-positive"
packages. These modem eJectrophysiologic instruments typi responses, especially with SEP, do correlate with transient post
cally have excellent noise reducing preamplification that needs operative paresthesias suggesting a partial injury, but given their
to be verified, as this is essential in the electrically noisy intra resolution, the study is considered a false-positive in terms of
operative environment. However, if just one modality is to be predicting permanent deficits. False-negative studies (maintain
assessed, such as SEPs, often the simplest of electrodiagnostic ing intact electrophysiologic responses, but the patients awaken
instruments can be used, though adequate performance again with new permanent neurologic deficits) are quite rare but do
should be verified in the operative suite. Such instruments may occur. 20,52.111.136.139.162.214,255.261.290,396,425 Many of these reported
not be as effective in rejecting noise and thus require longer av false-negative studies are not actually an electrophysiologic
eraging times, which results in less continuous monitoring. If false-negative because the monitored neurologic system was not
the attempts at intraoperative monitoring are going to be opti the system in which the deficit occurred. This emphasizes the
mized, the more sophisticated equipment becomes a necessity importance of the electrodiagnostic consultant's expertise in
in order to have adequate versatility, performance, and flexibil planning for effective intraoperative monitoring given the pro
ity to meet all demands. Specific equipment needs and proto cedure to be performed and potential structures at risk. An ex
cols are discussed further with each technique. ample is the use of SEPs, which specifically monitor sensory
446 - PART II BASIC AND ADVANCED TECHNIQUES
function and not motor function. 214 ,267 Another is the perfor entirely for approximately I of every 200 patients moni
mance of bilateral simultaneous peripheral nerve stimulation, tored.69.288.290 Given the enormous economic impact of paraple
which can lead to missing a rare hemicord dysfunction. 255 Other gia, the additional cost of intraoperative electrophysiologic
false-negatives are the late appearance of deficits that may re monitoring for even the fairly low risk procedure of scoliosis
flect the onset of edema or vascular insufficiency occurring surgery is cost-effective. One series of cervical spine surgeries
postoperatively, which could not be detected intraoperatively as compared 100 consecutive monitored cases with 0% subseq\lent
such impairments had not yet occurred. 162 adverse outcomes to the previous 218 unmonitored patients who
Often technical problems will lead to the loss of a signal intra had a 3.7% tetraplegia and 0.5% mortality adverse outcomes. 95
operatively. The search for such a technical problem must be Other disorders such as surgery for aortic coarctation (0.5%
made expediently. The location and integrity of the recording paraplegia incidence), thoracoabdominal aneurysms (up to 15 %
montage and technical system must be verified prior to alerting incidence of paraplegia), and surgical decompression for spinal
the surgeon as to a technical problem or an apparent electrophys cord tumors or trauma carry even higher risks (up to 20%) and,
iologic change. "Alert criteria" for clinically significant changes therefore, may benefit from intraoperative neurophysiologic
in the monitored responses often include a sustained loss, usu monitoring; however, such cost-effectiveness benefits have not
ally greater than 10 minutes, in part to allow investigation as to been studied as extensively.9.50,108,118
anesthetic, or technical problems than may have contributed to One assessment of cost versus liability applied the "learned
the observed changes.37M36 The clinical neurophysiologist must hand rule," which states that legal negligence occurs whenever it
verify the monitoring system's integrity and check with the anes would cost less to prevent a mishap than to pay for the damages
thesiologist for other factors,36 prior to concluding that a com predicted to result from it. 123 When restated in mathematical
promise in neurological function has been detected. Access to all symbols, whenever the cost (C) is less than the probablilty (P)
electrodes to verify correct positioning is necessary, though this multiplied by damages or the loss (L): C < P x L; then negli
is usually somewhat awkward and therefore is a contingency for gence has occurred if the cost, in this case of providing intraop
which one must plan in advance. erative neurophysiologic monitoring to such an at risk patient, is
Despite these cha])enges, significant reductions in morbidity not expended. Using one of the most reliable statistics we have,
have occurred from the increasing use of intraoperative electro that of the scoliosis group, if the risk is chosen as a very conserv
physiologic monitoring.287.29o Hearing loss has been pre ative value of 0.7% (P, without monitoring) and approximately
vented.24S.295.399,414 Paraplegia from scoliosis surgery has three quarters of a million dollars of loss occurs from paraplegia
declined from as much as 4-6.9% to 0-0.7% with the advent of (L) onset age 15,15 then any cost of less than $5240 per case to
intraoperative SEP monitoring.9S.2S1 The Multi-Center Study of provide intraoperative neurophysiologic monitoring should be
Spinal Cord Monitoring in Scoliosis Surgery found at least a expended in order to avoid this definition of negligence. II5 · 123
60% decline in morbidity with intraoperative monitoring during
scoliosis surgery, with serious neurologic deficits prevented
ANESTHESIA CONSIDERATIONS
Establishing intraoperative neurophysiologic protocols must
involve close cooperation with the anesthesiologist. Anesthesia
optimized to facilitate neurophysiologic monitoring will, never
theless, produce drug effects that alter sensory and motor
evoked responses that must be appreciated and appropriately in
terpreted by the monitoring neurophysiologist. Although some
generalizations exist about anesthesia drug effects, the relative
potency and specific location of drug actions differ between
agents, so that some discussion of each agent is necessary to
better understand the alternatives and their implications.
Some of the differences between anesthetic agents relate to
the anatomic site of the anesthetic effect. 329 Other differences
relate to the neurophysiologic site of drug action. The major
target for anesthetic action appears to be at the gamma
aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA)
receptors mediating electrolyte channels (Na+, Cl-, CA2+) at
central nervous system synapses.
In the sensory system, the response generated by synapses in
cortical structures will be the most affected, with less effect oc
~mD~~~~ curring at more peripheral structures, where fewer synapses are
MEDUL involved. 37 ! Because the most prominent anesthetic effects for
. ", mARALYSIS the sensory system is on the synaptic-rich cortically generated
lloo,.,.v responses, it is not surprising that anesthetic effects on cortical
J-t
1 sec.
"
- - - - - DEATH
GENERAUZED
SEIZURE SEP EEG
EFFECTS OF VARIOUS ANESTHETIC AGENTS n
ON AUDITORY EVOKED RESPONSE Awake
~
1 MAC ~ ~
~
1.5 MAC ~
B-S ~
Suppr.
1 MAC -----------
~
'------' 10 msec 1IN ]
~
~J
Figure 12-5. Cortical SEP and EEG recorded at various
doses of Isoflurane. (From Porkkala 1; Jantti V. Kaukinen S, Hakkinen
Figure 12-3. Cortical evoked potentials stages typical of V: Somatosensory evoked potentials during isoflurane anaesthesia.
anesthesia. (From Winters WD. Mori K. Spooner CEo Bauer RO: Acta Anaesthesiol Scand 1994;38:206-210. with permission.)
The neurophysiology of anesthesia. Anesthesiology 1967;28:65. with
permission.)
site may have one of two effects. First, partial synaptic blockade
may compound a loss of I waves, making it more difficult to
amplitude and increased latency of cortical SEP and myogenic bring the anterior hom cell to threshold. At higher doses, synap
motor evoked potential (MEP), making the anesthetic choice for tic blockade may inhibit synaptic transmission at this site re
monitoring with these electrophysiologic modalities particu gardless of the composition of the descending spinal cord volley
larly challenging. 372 of activity. The third major synaptic location for anesthetic ef
Based on the major effect of anesthetic drugs occurring at the fects in the motor pathway is at the neuromuscular junction.
synapses, three locations in the motor pathways will be the most Fortunately, with the exception of neuromuscular blocking
susceptible to anesthesia. The first location is within the motor agents and drugs, which alter acetylcholine transmission, anes
cortex where internuncial neurons and synapses participate in thetic drugs have little effect at the neuromuscular junction.
activation of the motor cortex by transcranial stimuli. When Similarly, neuromuscular blocking agents have little effect on
electrical or magnetic pulses activate pyramidal cells, they pro central nervous system synaptic transmission and axonal con
duce a direct activation of the cells producing a "D" wave and duction in motor pathways other than at the neuromuscular
activation via the internuncial pathways (dependent upon junction.
synapses) producing a series of I waves (Fig. 12-4). Weaker Finally, it should be noted that anesthetic drugs may have an
magnetic impulses appear to depend on synaptic activation for effect on evoked responses indirectly by altering other physio
production of a response. The implication of anesthetic effects logic factors that influence the provision of nutrient supply to
on these internuncial synapses is that the production of D waves the neural tracts. This is discussed in the sections that follow.
wil1 be relatively immune to anesthetic effects whereas the pro
duction of I waves will be reduced with anesthetic agents that INHALATIONALAGENTS
depress synaptic function. Of further consideration is that
synaptic function may be a delicate balance of inhibitory and Halogenated Inhalational Agents
excitatory influences. The second major sites of anesthetic Perhaps the most common anesthetics in use today are the
action in the motor system are the synapses at the anterior hom halogenated inhalational agents (desflurane, enflurane,
cell. At this location, the summated D and I waves bring the an halothane, isoflurane, sevoflurane). Paralleling their effects on
terior hom cell to threshold with a resulting peripheral nerve the EEG, all halogenated inhalational agents produce a dose-re
action potential leading to a muscle response. Anesthetics at this lated increase in latency and reduction in the amplitude of the
cortically recorded evoked potential responses (SEP, YEP,
BAEP). Although the effects of halogenated inhalational agents
appear to be dose related, the changes observed in some studies
appear to plateau at low concentrations (0.5-1 % inspired con
centration).339 Figure 12-5 shows the effects of isoflurane on
EEG and on the cortical SEP, demonstrating a parallel effect,315
Studies support differences in the potency of the halogenated
inhalational agents on the cortical SEP. The relative order seen
is isoflurane (most potent), enflurane, and halothane (least
potent).371 Studies with sevoflurane and desflurane suggest that
they are similar to isoflurane at steady state, but owing to their
more rapid onset and offset of effect (because of their relative
insolubility), they may appear to be more potent during periods
Figure 12-4. 0 wave and I waves with MEP stimulation. when concentrations are increasing.
448 - PART II BASIC AND ADVANCED TECHNIQUES
20 40 60 80
msec TIME (ms)
Figure 12-6. Influence of isoflurane alone on BAEP. Latency of
Figure 12-7. Motor evoked responses to transcranial electri
peaks III and IV-V increased at 1.0% but plateaued with increasing
cal stimulation during nitrous oxide/sufentanil anesthesia before,
anesthetic depth. (From Manninen PH, Lam AM. Nicholas JF: The ef
during, and after administration of isoflurane (0.3% end-tidal). (From
fects of isoflurane and isoflurane-nitrous oxide anesthesia on brain
Kalkman Cj, Drummond JC, Ribberink AA: Low concentrations of
stem auditory evoked potentials in humans. Anesth Analg 1985; 64:43.
isoflurane abolish motor evoked responses to transcranial electrical
with permission.)
stimulation during nitrous oxide/opioid anesthesia in humans.Anesth
Analg 1991;73:410.with permission.)
Nitrous Oxide
lOOms
Nitrous oxide produces SEP cortical amplitude reductions
and latency increases when used alone or when combined with Figure 12-10. Effect of nitrous oxide on cortical recordings
halogenated inhalational agents or opioid agents (Fig. 12-10). of posterior tibial nerve somatosensory evoked potentials. The ampli
Studies of nitrous oxide in a hyperbaric chamber confirm the tude of the response is markedly reduced over the I0-1 5 minutes fol
depressant nature of its effect at higher doses as well. 334 When lowing the introduction of nitrous oxide, and a response returns after
compared at equipotent anesthetic concentrations, nitrous oxide agent is removed. (From Sloan TB, Koht A: Depression of cortical so
produces more profound changes in cortical SEP and muscle matosensory evoked potentials by nitrous oxide. Br JAnaesth 1985;
recordings from transcranial motor stimulation than any other 57:850, with permission.)
450 - PART II BASIC AND ADVANCED TECHNIQUES
Despite the depressant effect of nitrous oxide, it has been INTRAVENOUS ANALGESIC AGENTS
used with recording of responses, particularly when combined
with opioids ("nitrous-narcotic" anesthetic technique). When Most anesthesia techniques utilize a mixture of different
combined with other agents, nitrous oxide may be "context-sen anesthetic agents such as supplementation with inhalational
sitive" in its effects, similar to its effects on the EEG (i.e., the agents (halogenated agent or nitrous oxide) with opioids or in
actual effect may vary depending on the other anesthetics al travenous sedatives (e.g., benzodiazepines, etomidate, droperi
ready present).249.369 dol. or propofol). If the inhalational agents need to be
As with sevoflurane and desflurane, nitrous oxide is rela completely avoided, intravenous agents can be combined to pro
tively insoluble. Therefore, anesthetic effects can change duce a total intravenous anesthetic (TIV A).
rapidly when concentrations are varied intraoperatively. Since a
decrease in concentration will be associated with a rapid in Opioid Agents
crease in amplitude and decrease in latency, it may "mask" am The effects of opioid analgesics (fentanyl, sufentanil, alfen
plitude and latency changes that may be occurring from tanil. remifentanil) on sensory and motor evoked responses are
concurrent neural compromise. Therefore, such changes should less adverse than inhalational agents, making them important
be avoided during critical portions of the surgery when the mon components of anesthetic planning for monitoring evoked re
itored structures may be at higher risk. sponses. 306 Effects are similar for most evoked sensory modali
Also, nitrous oxide can increase middle ear pressure and ties. Minimal changes in spinal or subcortical recordings are
hearing threshold, thereby presenting the possibility for dispro noted with some amplitude depression and latency increases in
portionate effects on BAEP and cortical auditory evoked poten cortical responses, especiaUy loss of late cortical peaks (over
tial (AEP) responses when eustachian tube dysfunction occurs. 100 ms) at doses sufficient to produce sedation (Fig. 12-11 ).184
This could result in false-positive monitoring deficits occurring As with systemic opioids, the spinal application of morphine or
in the BAEP. Therefore, avoidance of an increase in nitrous fentanyl for postoperative pain management produces minimal
oxide during critical portions of surgery requiring BAEP moni changes in the SEP and fails to alter the H-reflex. 345
toring is also important. Changes in such anesthetic agent con Opioid-based anesthesia is frequently used when cortical
centrations should be relayed from the anesthesiologist to the SEP responses and transcranial motor evoked potentials are
clinical neurophysiologist because they are required to help monitored. 305 Studies with myogenic responses from tcMEP
with correlating electrophysiologic monitoring changes to the with electrical and magnetic methods show only mild amplitude
operative environment. decreases and latency increases that permit good recording. 112.212
With respect to the latter, fentanyl has been suggested to be
useful in reducing background spontaneous muscle contractions
Cervical Cortical and associated motor unit potentials, which may further im
prove muscle recordings. Since the opioids do not guarantee se
dation or amnesia, opioid-based anesthesia must include an
additional sedative agent to produce TIVA.
Ketamine
The effects of ketamine on the evoked responses also differ
from those of inhalational agents. Ketamine can produce central
c
"E
-E
.5
nervous system excitement with associated enhancement of cor
tical sensory and myogenic responses. 369 Thus, an increase in
c: c: cortical SEP amplitude 345 and an increase in amplitude of mus
.2
.... 0 cle and spinal recorded responses following spinal stimulation
u 'fi.,
:~ :5'
i
o 25 o 60
Time (ms) Time (ms)
Figure 12-11. Changes in median nerve cervical and cortical Rgure 12-'2. Example of SCEP waveforms before and after
SEP recording with time in one patient after sufentanil 5 glkg. induction with ketamine at times 2.5. 10, 15.20. and 30 minutes.
Two baseline recordings at time zero are shown. (From Kimovec MA. (From Schubert A. Ucina MG, Lineberry PJ: The effect of ketamine on
Koht A. Sloan TB: Effects of sufentanil on median nerve somatosensory human somatosensory evoked potentials and its modification by ni
evoked potentials. Br JAnaesth 1990;65: 169. with permission.) trous oxide. Anesthesiology 1990;72:33. with permission.)
Chapter 12 INTRAOPERATIVE NEUROPHYSIOLOGIC MONITORING - 451
2
3
Figure 12-13. SEP responses recorded from the cervi
cal and cortical electrodes before (0) and at several times 4
up to 12 minutes following the injection of thiopentone (4
mg/kg). (From Sloan TB. Kimovec MA. Serpico LC: Effects of
5
thiopentone on median nerve somatosensory evoked poten 6
tials. Br JAnaesth 1989;63:51. with permission.)
7
8
9
40ms 50ms
has been seen. 174 This latter effect on muscle responses may be a silent EEG. For this reason, sensory evoked responses have
mediated by the same mechanisms that potentiate the H been used successfully to monitor neurologic function during
reflex.3.54 However, effects on subcortical and peripheral sensory barbiturate-induced coma (Fig. 12-13).362
responses are minimal (Fig. 12-12), Minimal effects are alsoob
served in myogenic tcMEP with ketamine. 112 Cervical Cortical
Because of these effects. ketamine is a desirable agent for
monitoring responses that are usually difficult to record under
anesthesia (e.g., dermatomal evoked responses and transcra
nially elicited muscle motor evoked responses). However, its
hallucinatory potential and known increase in intracranial pres
sure with intracranial pathology have led to a reluctance to uti
lize this agent routinely.
Sedative-Hypnotic Drugs
.....c:
Intravenous sedative agents are frequently used to induce or
supplement general anesthesia. If inhalational agents must be
avoided, sedative-hypnotic agents are routinely combined with
opioids or ketamine to ensure adequate sedation, anxiolysis, and
- E
c:
0
<;:.
4
~
amnesia. Although ketamine doses produce some dissociative :r...
effects in addition to analgesia, supplementation can reduce the
risk of excitatory events including hallucinations. ..
....~
QI
Droperidol
;
I-
When combined with fentanyl ("neurolept anesthesia"),
droperidol appears to have minimal effects on SEP. YEP, and
MEP.173 However, since its effect is quite long-lasting, many
anesthesiologists would prefer to utilize a more rapidly metabo
lized sedative hypnotic for TIVA.
Barbiturates
Thiopental remains a popular drug for anesthesia induction,
though transient decreases in amplitude and increases in latency o 30 0 50
of cortical sensory responses occur. Longer latency cortical TIme (ms) Time (ms)
waves are most affected. while minimal effects are seen on the
subcortical and peripheral responses. Studies with another bar Rgure 12-14. SEP responses recorded from the cervical and
biturate, phenobarbital, demonstrate that the BAEP is virtually cortical electrodes are shown before and at I-minute intervals after
unaffected at doses that produce coma; changes are not seen the injection of midazolam (.2 mglkg). (From Sloan TB. Fugina ML.
until doses sufficient to produce cardiovascular collapse are Toleikis JR: Effects of midazolam on median nerve somatosensory
reached. 242 Similarly, the SEP is unaffected at doses that produce evoked potentials. Br JAnaesth 1990;64:590. with permission.)
452 - PART II BASIC AND ADVANCED TECHNIQUES
---""""
I
10 12
10: 15:1Omg
ETOMDAT i.v.
10. 17
T1
10: 21
1O:~
21J~
J
+ II d5 Sb
t (ms I
SOMATOSENSORISCH EVOZIERTE POTENTiAtE ISEPI
Time lmo'
NACH tEOIANUSSTIMULATION
i 1.0
Regional Anesthesia E
<
Major conduction anesthesia (e.g., epidural or spinal) does !'t
' ill 0.5
not appear to be an acceptable alternative to general anesthesia Qi *
a:
for monitoring evoked responses that depend on the tracts anes *
thetized.371 This effect has also been seen with intravenous re 0
0.2 0.4 0.6 0.8
gional block and specific nerve blocks. However, local Fraction EMG Remaining
anesthesia placed away from the neural pathway mediating the
monitored evoked response (such as scalp anesthesia for awake Figure 12-/7. Plot of tcMMEP amplitude as recorded from
craniotomy) is satisfactory for monitoring unless systemic ab thenar muscles as plotted versus the fraction of a. single twitch re
sorption is substantial. maining following median nerve stimulation. (From Sloan TB. Erian R:
Effect of atracurium induced neuromuscular block on cortical motor
Muscle Relaxants evoked potentials.Anesth Analg 1993;76:979, with permission.)
Since muscle relaxants have their major site of action at the
neuromuscular junction, they have little effect on electrophysio
logic recordings such as the SEP that do not derive from muscle OTHER INTRAOPERATIVE
activity. In fact, they may improve, or be essential for, some PHYSIOLOGIC FACTORS
types of recordings where the muscle activity near the recording
electrode may create unwanted noise. This is true for epidural BLOOD FLOW
or peripheral nerve recordings where the activity of overlying
muscle obscures the response from transcranial stimulation. For As measures of neural function, the evoked responses are re
recording of these responses, complete or near-complete neuro sponsive to a variety of physiologic factors that alter neuronal
muscular blockade is highly desirable. function and viability. Numerous studies I4 ,28,29,33.392,394 have
Certainly, complete neuromuscular blockade will prevent demonstrated a threshold relationship between regional cerebral
recording of CMAP responses during MEP. However, partial blood flow and cortical evoked responses. The cortical SEP re
neuromuscular blockade has the benefit of reducing a substan mains normal until blood flow is reduced to about 20
tial portion of the movement that accompanies the testing. Some mllminllOO gm. 360 At more restricted blood flows of between 15
degree of neuromuscular blockade may facilitate some surgical and 18 mllminllOO gm of tissue, the SEP is altered and lost
procedures where muscle relaxation is needed for adequate (Fig. 12_18).31,32.64,119,134.193,213 Subcortical responses appear less
tissue retraction. sensitive, though global hypotension, affecting both subcortical
Two methods are customarily utilized to assess the degree of and cortical blood flow, is associated with cortical SEP loss at
neuromuscular blockade. The method that best quantitates the higher rates of cerebral blood flow than with middle cerebral
blockade involves measuring the amplitude of the CMAP (TI) artery occlusion, which more selectively impairs cortical than
or M-wave produced by supramaximal peripheral motor nerve subcortical blood flow} 19,213 The difference in sensitivity to is
stimulation. When neuromuscular monitoring is conducted this chemia between cortical and subcortical structures may explain
way, most monitoring protocols use neuromuscular blockade of why the central conduction time (CCT) of the SEP bears a
Tl that is 10-20% of baseline. Clinically, anesthesiologists parametric relationship to cerebral blood flow (Fig. 12-18).103.134
often assess neuromuscular blockade by counting the number of Regional factors may produce focal ischemia not predicted
twitches remaining when four motor nerve stimuli are delivered by systemic blood pressure. For example, during spinal surgery,
at a rate of 2 Hz. Measured this way, acceptable CMAP moni the effects of hypotension may be aggravated by spinal distrac
toring has been conducted with only 2 of 4 responses remain tion, such that an acceptable limit of systemic hypotension
ing47 (this corresponds to a Tl response in the range of cannot be determined without monitoring. 35•82 ,120.122 Other
10-20%). When intense neuromuscular blockade is required examples include peripheral nerve ischemia from positioning,
(e.g., recording of epidural or neurogenic responses), T1 re
sponse of less than 10%, or no more than 1 of 4 twitches, is gen
erally recommended. )-
NORMAl.
When using neuromuscular blockade, tight control of the !: flg-2(»)
!:
blockade is necessary so that excessive blockade. does not elim
inate the ability to record or mimic the loss of the response with !
neural injury (Fig. 12-17), creating a false-positive result. 366
Because of varying muscle sensitivity to muscle relaxants, the
neuromuscular blockade may need to be evaluated continuously
in the specific muscle groups used for monitoring. It is impor ASS£HT c/:/min//OO
tant to note that the use of neuromuscular blockade is controver () 10 20 .J $()
sial during monitoring of muscle responses from mechanical Ra8l0f4AL CEREBRAL BLOOD FLOW
stimulation of nerves, as partial paralysis may reduce the ability
to detect these responses (e.g., facial nerve monitoring or moni Figure'2-1I. Relationship between the SEP and EEG elec
toring for pedicle screw placement). Often muscle relaxants are trical response and regional cerebral blood flow. (From Sloan T:
avoided when monitoring these latter mechanically evoked American Society of Anesthesiologists: Refresher Courses. October
muscle EMG neurotonic responses. 1985, Lecture 21 I. with permission.)
454 - PART II BASIC AND ADVANCED TECHNIQUES
~800
:I: r o O.84
E
5600 .'
Q.
u
4
frequently drop by greater than 1°C, but peripheral nerves gradually came into use. The intraoperative application and
lifted from the body for focal stimulation may be as cool as clinical utility of EEG, BAEPs, SEPs, and EMG in a variety of
20o_30°C. 38 different surgical procedures are discussed below. The clinical
Whole body hypothermia, either inadvertent or intentional, is utility of VEPs is very limited; therefore, VEPs will be only
the most obvious temperature change that occurs during briefly discussed.
surgery. Changes in regional temperature can also occur, result The cortical EEG is produced by the spontaneously gener
ing in evoked response alterations that would not be otherwise ated electroencephalographic brain wave activity and is easily
predicted based on unchanged body (core) temperature. For ex recorded, requiring no stimulus. However, evoked potential
ample, cold irrigation solutions applied to the spinal cord,61 (EP) recordings can only be generated by applying an external
brain stem, or cortex routinely cause evoked response changes. stimulus. In general, stimulation is provided peripherally using
These cold irrigation solutions may also irritate the nerve, caus peripheral nerve electrical stimulation for SEPs, auditory clicks
ing increased muscular activity if the nerve has motor compo for BAEPs, and light flashes for VEPs. In addition to recording
nents.256 Similarly, limb cooling (as from cold intravenous EPs, spontaneous or stimulus triggered EMG can be recorded
solutions) can alter the SEP originating from stimulation to a from muscle using either intramuscular or surface electrodes.
nerve from that limb. Electrical or magnetic stimulation of peripheral nerves, nerve
With hypothermia, the tcMMEP demonstrates a gradual in roots, spinal cord, cranial nerves, or cortical structures can gen
crease in onset as temperature decreases from 38°C to 32°C erate a motor evoked response that also can be recorded from a
esophageal. An increase in stimulation threshold has also been muscle or nerve.
observed at lower temperatures. This is consistent with both
cortical initiation and peripheral conduction being affected by ISCHEMIAAND ELECTROPHYSIOLOGIC STUDIES
the temperature drop. 364
Different techniques have been used in order to identify and
OTHER PHYSIOLOGIC VARIABLES attempt to prevent damage caused by cerebral ischemia. The
most extensively studied and commonly used techniques are
Changes in a variety of other physiologic variables may EEG and SEPs. The rationale for employing electrophysiologic
produce alterations in the evoked responses during surgical techniques as a marker for ischemia is the good correlation be
monitoring. Significant reduction in blood volume can alter tween these techniques and regional cerebral blood flow
evoked responses as a result of changes in blood flow distribu (rCBF). As previously noted, studies demonstrated that in pa
tion, despite absence of significant blood pressure changes tients undergoing carotid endarterectomies (CEA), major EEG
(e.g., limb ischemia altering the SEP as blood flow to central changes occurred with rCBF < 10 mlliOO gm/min, and less
organs is spared). An increase in superior vena caval pressure severe EEG changes were seen with rCBF between 10 and 18
during cardiopulmonary bypass has been associated with SEP mUl00 gm/min, with a critical level defined as 15 ml/IOO
changes. 148 gm/min. 352,386.387 In contrast, primate studies show that SEPs are
Other physiologic events may occur too slowly to be noted as maintained at levels of rCBF ~16 mUloo gm/min but absent at
changes in the evoked response. For example, changes in glu levels below 12 mUloo gm/min. At rCBF levels between 14 and
cose,74 sodium, potassium, and other electrolytes important in 16 mIlloo gm/min, there is a sharp decline in the evoked re
the neurochemical environment are likely to also result in sponse amplitude, with a 50% amplitude reduction correspond
evoked response changes over time. ing to a rCBF of 16 mIl100 gm/min.28.30.32.391 In addition to
altering the SEP amplitude, ischemia also appears to prolong
the CCT, with a threshold rCBF «15 mUlOO gm/min) similar to
INTRAOPERATIVE NEUROPHYSIOLOGIC those previously reported for EP amplitude reduction. 134.213
MONITORING: SPECIFIC APPLICATIONS Interestingly, there is experimental evidence suggesting a dif
ferential susceptibility to local ischemia as one descends the
As previously noted, intraoperative monitoring (10M) can neuraxis, demonstrated by increasing resistance of eJectrophysi
be described as the application of neurophysiologic, usually ologic function to systemic hypotension. 32
electrophysiologic, techniques to detect changes in the func There clearly seems to be a threshold relationship between
tional state of the nervous system consistent with ischemia or cerebral blood flow and alteration of the EEG and SEP. There is
injury. Electrophysiologic techniques may also assist in localiz also a good deal of experimental evidence for a rCBF threshold
ing neural structures, identifying specific cortical functional and cellular membrane failure.15.391 An investigation has found
areas, and delineating an epileptogenic cortex. The information that at rCBF levels between 12 and 16 mUloo gm/min, the SEP
obtained may also help determine the mechanism of injury, cor was abolished and small, self-limiting increases in extracellular
related with the surgical proceedings, and serves to prevent potassium activity were detected. 30 This study further demon
damage by detecting cellular dysfunction prior to its reaching strated that the rCBF threshold range for a massive irreversible
an irreversible cell death stage. Outcome studies have in general rise in extracellular potassium, associated with structural
been promising in that intraoperative electrophysiologic studies changes of infarction, occurred between 7.6 and 11.4 mIlIOO
do make a positive difference in patient care.69.245,287.290.295.399.414 gm/min. In baboon chronic stroke models, following middle
Intraoperative neurophysiologic monitoring for surgical pro cerebral artery (MCA) occlusion, areas of infarction corre
cedures where the central and peripheral nervous systems are at sponded to blood flow levels of 10 mllloo gm/min or less.390.391
risk has become increasingly popular over the past several In acute stroke primate models, infarction occurred only in
years. 10M of facial nerve activity, utilizing EMG, was first per areas where rCBF measured ~ 12 mIll 00 gm/min (Table 12
formed in the late 19th century, and EEG was subsequently used 12).167.186.260 Thus, these findings suggest that significant (50%)
in 1965.310 Other electrophysiologic techniques such as SEPs, reduction in amplitude of the SEP, which corresponds to a rCBF
BAEPs, VEPs, and peripheral nerve compound action potentials of 14-16 mlllOO gm/min, is indicative of ischemia and is a
456 - PART II BASIC AND ADVANCED TECHNIQUES
-, H'0!illll!ll_'"
~
, , . r 'Yp
"
- - - -
These types of displays allow for easier interpretation of the cortex, which is supplied by the MCA and thus is at risk
EEG, showing ischemic changes as loss of amplitude in the during carotid cross-clamping. There are also several technical
power spectrum for all frequencies and a shift of the EEG spec advantages of SEPs over EEG for 10M, such as relative resis
trum to the lower frequency range. Several studies using com tance to general anesthesia, fewer electrode sites, easier
puterized EEG analyses have found the technique useful in recording and interpretation, and serial comparison,76.2oo,241
identifying cerebral ischemia and predicting neurologic out Moorthy et a1. were the first to report the use of median nerve
come following CEA.4,55.319.320 In fact, some investigators have SEPs during CEA and to correlate SEP changes with neuro
claimed that computer-processed EEG proved more useful than logic deterioration. 259 Subsequently, Markand reported on 38
analog EEG.4.55 However, a prospective study of 103 patients CEAs monitored with SEP.240 One patient had a sudden loss of
undergoing CEA monitored with analog EEG and DSA con consciousness and loss of the cortical SEP following carotid
cluded that DSA was not sufficiently sensitive in detecting lim cross-clamping. The SEP changes were reversed, and the pa
ited cerebral ischemia associated with mild analog EEG tient regained consciousness after shunt placement. In three
changes. 179 Thus. it appears that there is a role for computerized other cases, shunting reversed SEP changes. Other investiga
EEG analysis during CEAs, with the caveat being that it may tors have reported on the reliability and accuracy of SEPs in
lack sensitivity in detecting mHd EEG real-time pattern changes CEAs.1,76.11O,138.118.333,341,404 However, at least one study has con
consistent with cerebral ischemia. cluded that SEPs are not sensitive enough markers of cerebral
ischemia because neither 50% amplitude reduction nor in
Somatosensory Evoked Potentials crease in CCT has been established as a physiologic marker of
As previously mentioned, there is a strong correlation be intraoperative ischemia in humans. 2OO However, in this study
tween SEPs and cerebral ischemia; therefore, SEPs have SEP criteria were measured against the EEG "gold standard"
gained popUlarity as a useful 10M technique to assess cerebral instead of using neurologic outcome as an endpoint. The in
function during cerebrovascular surgery.IS8 Median nerve vestigators found that 10 out of 23 patients with EEG evidence
SEPs reflect the cerebral functional status of the primary sensory of ischemia after cross-clamping had prolongation of the CCT
458 - PART II BASIC AND ADVANCED TECHNIQUES
......
0"'0_
0 .....v
...... '
_0.. _, .
....... i
.
I
'
A ~B______________~I~ ____________~
Figure '2·22. . 2S-year-old female admitted for clipping of a
giant right MCA trifurcation aneurysm who presented with left
face and arm numbness.
Trace I: Right cortical SEP (C 4'-Fz) after left median nerve stimula
tion
Trace 2: left Erb's EP (left Erb's-fz) after left median nerve stimula
tion
Trace 3: left cortical SEP (C)'-Fz) after right median nerve stimula
tion
Trace 4: Right Erb's EP (right Erb's-fz) after right median nerve stim
ulation
A. Baseline SEPs. B, loss of right cortical SEP 2 minutes after tempo
rary clipping of the MI branch of the right MCA. C, Recovery of corti
cal SEP 2 minutes after temporary clip was removed. Patient
experienced no new postoperative neurologic deficits.
but only one had amplitude reduction of 50% or more. In con Intraoperative SEP Changes:
trast, another group stated that there is a higher incidence of Ischemia. As noted above, severe cerebral ischemia causes a
false-positives and the use of shunts with EEG, since there is reduction of the cortical SEP amplitude to s 50% of the base
less agreement in identifying EEG evidence of ischemic risk line value. In addition, the peak latency of the cortical SEP can
as compared with SEPsJ Although SEP criteria for cerebral be delayed and the CCT prolonged.
ischemia are not uniform and differ among various investiga Temperature. Hypothermia can prolong the latencies of all
tors, with some using amplitude reduction, latency delay, or peaks and needs to be taken into consideration because surgery
specific prolongation of CCT or a combination of the three to frequently leads to a I-3°C drop in the core body temperature.
signify cerebral ischemia, most studies have found that a 50% Hypotension. Can lead to amplitude reduction and/or delay
amplitude reduction of the NI9-P24 or a I-millisecond delay in the cortical SEP latencies. Critical level depends on the pa
of the CCT correlates best with postoperative neurologic tient's preoperative blood pressure.
deficits.34.77.110.142.178.179.344 Interventions. The interventions performed when SEP
A review of seven studies comprising 3028 patients re changes occur are similar to those described for EEG changes.
ported that 170 patients, or 5.6%, had a significant decline in Installation of a shunt is the most common strategy. However,
intraoperative SEPs that correlated with surgical manipula head repositioning and restoration of blood pressure may also
tion and that 34, or 20%, of the 170 patients developed signif be used.126.318
icant postoperative deficits. 99 Additionally, the reported
sensitivity and specificity in six studies, between 1985 and INTRACRANIAL NEUROVASCULAR SURGERY
1991, were 83-100% and 83-99%, respectively.2°O It was con
cluded that conventional EEG and SEP monitoring modalities The type of e\ectrophysiologic technique to be used de
during CEAs have similar sensitivity and specificity. A sepa pends on several factors, such as type of surgery, anatomic lo
rate study found that intraoperative SEP amplitude decre cation, intracranial vascular supply at risk, and preoperative
ments of 50% or more were associated with worsening of neurologic deficits. EEG monitoring has had limited use in
neurophysiologic function, determined by comparing pre aneurysm surgery because craniotomy and brain relaxation
and postoperative neurophysiologic testing. 34 These findings produce air spaces between the dura and arachnoid that inter
suggest that SEP 10M is useful in improving neurologic out fere with recording of the EEG.93 However, a combination
come during CEA (Fig. 12-21).50 of EEG and SEPs can be used to monitor MCA aneurysm
Chapter 12 INTRAOPERATIVE NEUROPHYSIOLOGIC MONITORING - 459
10. 1.05
I~~,~~~~~r+~~~-rrln~
n
.,.",
,.;,
A ,B
Figure '2-23. 48-year-old male presented with a 2.2-em anterior eommu"'Ileatlng artery aneurysm after a subarachnoid hemor
rhage.
Trace I: Right cortical (C",'-Fz) SEP after left median nerve stimulation
Trace 2: Left Erb's (C4 '-ipsilateral Erb's) SEP after left median nerve stimulation
Trace 3: Left cortical (C3'-Fz) SEP after right median nerve stimulation
Trace 4: Right Erb's (C 3'-ipsilateral Erb's) SEP after right median nerve stimulation
Trace 5: Right cortical (Cz-Fz) SEP after left posterior tibial nerve stimulation
Trace 6: Right cortical (Cz'-Fz) SEP after left posterior tibial nerve stimulation
Trace 7: Left cortical (Cz-Fz) SEP after right posterior tibial nerve stimulation
Trace 8: Left cortical (Cz'-Fz) SEP after right posterior tibial nerve stimulation
A. Baseline intraoperative SEPs. B, Five minutes after temporary clips were applied to both A I arteries, there was a 50-(,5% amplitude reduction
in the cortical SEPs after right leg stimulation. C, Removal of the temporary dips resulted in recovery of the SEPs over 21 minutes.The patient did
not develop any postoperative new neurologic deficits.
surgery.304 The EEG was used to detect burst suppression pat ANEURYSM
terns, thus allowing for the minimal dosage of thiopental re
quired to achieve neuroprotection, while SEPs monitored Middle Cerebral Artery/Internal Carotid Artery
cerebral ischemia. A review of the reported clinical outcomes in 10 studies in
MCA and internal carotid artery (lCA) vascular territories volving MCA aneurysm surgery demonstrated the reliability of
can be monitored with median nerve SEPs, since the so median nerve SEPs in predicting outcome, which ranged from
matosensory cortex representing the hand is supplied by the 78-100%,303 An investigation of intraoperative monitoring in 50
MCA. In addition, median nerve SEPs also provide informa aneurysm surgeries (12 MCA) reported that a CCT greater than
tion on the posterior cerebral artery (PCA) vascular territory 9 milliseconds (ms) correlated with postoperative neurologic
through the monitoring of thalamic activity.39 Several studies deficits,?7 In addition to prolongation of the CCT, another study
have demonstrated the utility of median nerve SEPs in pre found that a decrease in cortical SEP amplitude or disappear
dicting postoperative neurologic outcome. 39.40,81,104,105,248,258,343, ance of the cortical EP accurately predicted postoperative
392.393 deficits.104 A study of 53 MCA aneurysm procedures found new
460 - PART II BASIC AND ADVANCED TECHNIQUES
"..
A
B
Traces 7 and 8: left cortical SEPs (Cz-Fz and Cz'-Fz) after right
postoperative deficits in the following: four out of four patients identifying significant ischemia due to accidental clipping of
with a significant change in the SEP and incomplete return to blood vessels, manipulation of brain structures, and excessive re
baseline or loss of the EP; and one out of five patients with signif traction. 81 .343 In a study of 134 aneurysms, there was reported
icant SEP changes that returned to baseline. lOS In contrast, only loss or alteration of SEPs in 12 cases of temporary occlusion,
one out of 37 patients without SEP changes developed a new post two cases of accidental clipping, one case of permanent occlu
operative deficit. An investigation monitoring 37 patients undergo sion, and one case each of retraction of the MCA and cerebellar
ing aneurysm surgery (17 MCA) concluded that preservation of retraction. 343 In 15 out of 17 instances of SEP changes, the surgi
conduction, even if CCT increased to 10 ms, was associated with a cal course was altered. Changes included repositioning of vascu
good outcome. 393 However, prompt disappearance of the N20 lar clips and repositioning of retractors. In rare instances, cortical
(within 1 minute), as well as slow recovery of the SEP (> 20 min SEP changes may identify a peripheral ischemic process such as
utes), was associated with new postoperative deficits. a malfunctioning blood pressure cuff causing arm ischemia. !Os
In an attempt to determine the permissible temporary occlu
sion time in aneurysm surgery, a retrospective analysis of the re Anterior Cerebral Artery (ACA)
sults of 10M with median nerve SEPs in 97 patients undergoing A study found median nerve SEPs to be poor indicators of is
MCA and ICA surgery found the loss of the SEP in 42 patients chemia in anterior communicating artery (ACA) vascular terri
during temporary occlusion, with all but three patients recover tory.2S8 The most likely reason for lack of change is because the
ing the SEP back to baseline levels after recirculation. 253 The ACA vascular distribution does not supply the median nerve so
three patients who did not recover their SEP experienced a rapid matosensory cortex, and the cortical generators of the P40-N45
loss of the SEP (between 1 and 5 minutes) and developed post posterior tibial SEPs lie within the vascular territory of the
operative deficits. One patient without SEP changes developed ACA. Some investigators recommended SEP monitoring using
postoperative hemiplegia. The authors concluded that tempo posterior tibial nerve stimulation combined with median nerve
rary vascular occlusion is relatively safe for a period of approx stimulation, since posterior tibial nerve SEPs are inadequate in
imately 10 minutes after gradual loss of the SEP (Fig. 12-22). detecting ischemia in the recurrent artery of Heubner. 343 More
In addition to providing information about the development of recently, in a small series of 15 patients, posterior tibial nerve
cerebral ischemia during temporary clipping, SEPs are useful in SEPs were used during ACA surgery requiring temporary arterial
Chapter 12 INTRAOPERATIVE NEUROPHYSIOLOGIC MONITORING - 461
_..,......:... .......,.y;
"t..kk55p;;;.;;~:-.,~gi.======51":-:-;. °_-=========::::11
s;ocAII
occlusion to identify the onset of cerebral ischemia. 338 Sig had BAEP changes associated with a new neurologic change. 225
nificant SEP changes were seen in 11 of 15 patients. Unilateral However, lout of 17 patients had a new neurologic deficit de
A I (first branch of the ACA) occlusion led to SEP changes in spite no change in BAEP (false-negative). The investigators
four out of seven patients, while bilateral A 1 occlusion caused
changes in six of eight patients (Fig. 12-23).
Posterior Circulation
Several investigators have found 10M of vertebral-basilar
aneurysms with SEPs and BAEPs to be unreliable. 105.219.258 A
possible explanation is that ischemia, owing to basilar perforator
occlusion, may not affect the brainstem auditory or somatosen
sory pathways.93.105 However, one team of investigators found
that dual-modality monitoring (SEPs and BAEPs) was useful
during posterior fossa aneurysm surgery.239 They examined a
total of 70 aneurysms of the vertebral basilar circulation and
found that 10 patients had a change in their BAEP with six de
veloping a postoperative neurologic deficit. Fourteen patients
had SEP changes, and eight of these had new postoperative
changes. All patients who had permanent EP changes developed
postoperative neurologic deficits. They also reported that the in
cidence of false-negative and false-positive results for both
modalities was 20% and 30%, respectively. These findings sug
gest that identification of brain stem ischemia with 10M is en Figure '2-26. 25-year-old male with pontine glioma resec
hanced by using a dual-modality approach. A recent study using tion. Intraoperative monitoring of this case involved multi modality
multimodality (SEP and BAEP) monitoring for both anterior and recordings of the following:
posterior circulation aneurysms showed that posterior circulation Trace I: BAEPs after left ear stimulation
ischemic changes as well as anterior circulation ischemia were Trace 2: Right cortical SEP (C4 '-Fz) following left median nerve stim
Table 12·13. Muscles Accessible for Cranial Nerve concluded that SEP and BAEP changes were useful in predict
EMG Monitoring ing postoperative neurologic function (Fig. 12-24).
Cranial Nerve Muscles
III Inferior rectus BRAIN TUMOR SURGERY
IV Superior oblique The techniques used to monitor brain tumor surgery deJJ.end
V Masseter on the location and extent of the tumor. If the tumor is located in
the cerebrum, 10M usually involves identifying the functional
VI Lateral rectus sensory and motor cortex. This can be achieved by directly
VII Frontalis, orbicularis oculi, stimulating the cortex and observing or recording motor activity
and orbicularis oris in the face, arms, or legs of an anesthetized patient. Cortical
IX
Posterior pharyngeal muscles stimulation in an awake patient can also be used to identify the
cortical areas corresponding to language. Another method is to
X
Cricothyroid or vocalis electrically stimulate a peripheral nerve (usually the median
XI
Sternocleidomastoid or trapezius and/or posterior tibial) in a fashion similar to that used for SEPs
and record a "phase-reversal" directly from the cortex (Fig. 12
XII
T T
R
C
3m.Tri.g
100 uV Amp 1
21-----_
3 "' .. Tr 'g
100 uV Amp 3 100 uV Amp 3
3
"'. Tr ig :3 m. Tri.g
4~-----------t~------------~~------~---1
100 uV Amp 4 100 uV Amp 4
6
01'f
6
0.,.,
01'f 01'f
7 7
01'1'
8 B
A B
Di..k Sp. . . . :O r S03P1B 10.HI o i..k Sp.c.: 0 _ _ _ _ _ _ _ _ _ _ _ _--'1 S03P1B 10.HI
Figure 12-27. A 55·year-old female undergoing resection of a pontine AVM was monitored for cranial nuclei activity. The facial nerve
nucleus was localized using monopolar electrical stimulation prior to incising the pons. Evoked CMAPs were recorded using intramuscular hook
wire electrodes placed in the following muscles:
Trace I: Left orbicularis oculi
Trace 2: Left orbicularis oris
Trace 3: Left masseter
Trace 4: Right orbicularis oculi
Trace 5: Right orbicularis oris
A, Brain stem stimulation (1.0 mAlO.OS msec) showing a small response from the left orbicularis oris. B. Slight caudal movement of the stimulation
electrode reveals larger CMAP indicating the location of the nucleus. Stimulation parameters remained unchanged from the previous trace. The
AVM was not resected because it did not come to the surface and it was located directly beneath the nucleus.
Chapter 12 INTRAOPERATIVE NEUROPHYSIOLOGIC MONITORING - 463
negative-positive electrical potential, while the EP, recorded defining them as "distinctive discharges of a motor unit poten
from the precentral gyrus appear as a mirror image biphasic po tial in rapid, irregular bursts" (Fig. 12_27).68.292 In contrast,
tential (positive-negative).325 Using the phase-reversal tech CMAPs monitor integrity and continuity of the nerve from the
nique, a cortical strip or grid is placed on the cortex, in an area point of stimulation (proximal to the site of surgery) to the
thought to correspond to the somatosensory and motor cortex. muscle. The onset latency of the CMAP indicates the conduc
Peripheral nerve stimulation will produce a sensory EP easily tion time of fastest fibers, while its amplitude is approximately
recorded from the exposed cortex. If the cortical grid is lying proportional to the number of available axons. l13a. l85
across the sylvian fissure, a corresponding electrical potential of CN VIII. The need to preserve hearing in surgeries of the
opposite polarity can be recorded from the motor cortex. This cerebellopontine angle and in acoustic neuroma resections has
technique is relatively fast, reliable, and simple to perform. led to a variety of auditory evoked potential techniques. m .l5l
Tumors in the posterior fossa and in areas adjacent to cranial The most commonly used recording technique is the BAEP;
nerves will usually require multimodality monitoring using a however, other less commonly used techniques such as electro
combination of SEPs, BAEPs, and spontaneous and/or triggered cochleography (ECoG) and direct recording of nerve action
EMG (Fig. 12-26). potentials (NAP) are useful in assessing eighth nerve func
tion.151 The advantage of the BAEP is that it reflects the electri
POSTERIOR FOSSA AND CRANIAL NERVE SURGERY cal activity in the auditory nerve and auditory pathways of the
brain stem in response to cochlear stimulation. Five distinct
Posterior fossa surgery presents difficult and unique chal vertex positive waveforms can be recorded, with waves I, III,
lenges to the 10M team because various types of surgeries are and V being the most significant for 10M purposes. Waves I and
performed, each requiring a different monitoring protocol. II originate from the auditory nerve at the level of the cochlea,
Thus, the 10M protocol is designed according to the neural wave III within the lower pons, and wave V in the midbrain near
structures at risk. The most commonly used modalities are the inferior co11iculus. 53 Direct intracranial recordings NAPs
BAEPs, spontaneous and triggered EMG, and SEPS.53 It is can be obtained using a small cotton-wick electrode applied to
common to use these modalities simultaneously in order to the eighth nerve close to its entrance to the brain stem. The
monitor a larger group of neural structures. ECoG is the least commonly used modality and can be recorded
The most common use of 10M in posterior fossa surgery is using a needle electrode placed through the tympanic mem
for acoustic schwannoma resections, but monitoring is also uti brane and resting on the promontory of the middle ear. ECoG is
lized in surgeries for other types of tumors, hemifacial spasm, used to document integrity of the cochlea.
trigeminal neuralgia, and vascular structures. For monitoring CN VIII function, the BAEP seems to be the
Monitoring Cranial Nerve (CN) I. Monitoring of the most comprehensive modality because it assesses peripheral
visual pathways has been attempted using VEPs. However, and central auditory pathways, has few technical limitations,
VEPs are very sensitive to technique, anesthesia, temperature, can be used during the entire procedure, and has good correla
blood pressure, and other surgical factors and are affected in an tion with postoperative hearing status (Table 12_14).139.215 In a
unpredictable manner.99.382 One investigator stated that flash study of 90 BAEP-monitored patients compared with 90 un
VEPs are not useful for 10M during removal of visual pathway monitored historically matched controls undergoing acoustic
lesions, owing to a combination of uneventful monitoring, false neuroma surgery, it was found that BAEP monitoring reduced
positive, and false-negative cases. 382 the risk of hearing loss in patients with acoustic neuromas less
CNs III-VII and IX-XII. 10M of the motor component of than 2 cm and was statistical1y significant for tumors less than
any cranial (or peripheral) nerve is performed in essentially the 1.1 cm in diameter.l 39 In addition, BAEP monitoring improved
same fashion. The basic principle involves EMG monitoring of the chance of preserving useful hearing.
spontaneous and triggered muscle activity. Obviously, the cra Owing to the close proximity to CN VII to acoustic neuro
nial nerve(s) at risk will determine which muscles from which mas, techniques to also monitor this cranial nerve during
to record (Table 12-13). Recordings can be obtained by placing acoustic neuroma resections have been described. 62,63,l35
two intramuscular wire electrodes within the muscle or using
surface electrodes. Simultaneous spontaneous EMG and INTERVENTIONAL NEURORADIOlOGIC PROCEDURES
CMAP recordings can be obtained by using intramuscular wire
and surface electrodes. Using intramuscular electrodes in There are few reports of 10M monitoring in neuroradiologic
creases the sensitivity for detecting spontaneous EMG activity, procedures.57.79.128.302,307 However, EEG and EPs have been
while surface electrodes allow for more reliable monitoring of
CMAP amplitude and morphology.68,1I3a Additionally, a sen Table 12-14. Hearing Outcome As a Function of Presence
sory nerve conduction study has been applied for intraoperative of Evoked Potentials at End of 164 Cerebellopontine Angle
CN V monitoring. l56 Tumor Operations
Also, brain stem cranial nerve nuclei can be identified and
mapped by electrically stimulating discrete areas of the brain NI Present N I Not Present
stem. For example, direct stimulation of areas within the floor Wave V present Hearing (31) ** (none)
of the fourth ventricle can activate the trigeminal and facial Wave V not present Indeterminant (66): No hearing (67)
nuclei. Recording is performed in a manner similar to that de "Useful" hearing (38)
scribed above (Fig. 12-27). Not "useful" hearing (12)
The rational for using spontaneous EMG activity monitoring No
is based on the property that thermal, mechanical, or metabolic
From Levine RA: Monitoring auditory evoked potentials during cerebellopon
irritation of the intracranial portion of the motor CNs will lead tine angle tumor surgery. In Schramm J. Mllliler AR (eds): Intraoperative Neuro
to characteristic activity in the innervated muscles.54.l07.328a physiologic Monitoring in Neurosurgery. New York, Springer. 199 I. pp 193-204.
Some investigators termed this activity "neurotonic discharges," with permission.
464 - PART II BASIC AND ADVANCED TECHNIQUES
RIOO
.
uY
20.2
Figure 12-28. An 80-year-old female with a giant basilar aneurysm and recent subarachnoid hemorrhage treated with en
dovascular occlusion. The patient was believed to be a poor surgical candidate, and endovascular placement of coils was not possible owing to
the morphology of the aneurysm. Basilar or vertebral occlusion, as a means of reducing arterial flow and to promote thrombosis of the aneurysm,
was determined to be the best option.
Trace I: BAEP (A1-Cz) after left ear stimulation
Traces 2 and 3: Right cortical SEPs (C4-Fz and e,...-C).) after left median nerve stimulation
Trace 4: Left Erb's (left Erb's-fz) following left median nerve stimulation
Trace 5: BAEP (A2-Fz) after right ear stimulation
Traces 6 and 7: Left cortical SEPs (C 3'-fz and C]·-C.,,) after right median nerve stimulation
Trace 8: Right Erb's (right Erb's-Fz) following right median nerve stimulation
A, Baseline BAEPs and SEPs. a, Three minutes after balloon occlusion of the basilar artery. Note loss of left cortical SEP and delay and reduced
amplitude of right cortical SEPs. No significant changes were seen in the BAEPs. C, Return of SEPs to baseline levels 5 minutes after the balloon
was deflated. Occlusion of the right vertebral artery produced no significant changes in the evoked potentials, and, therefore, it was permanently
occluded. The patient experienced no new neurologic deficits.
successfully used in the monitoring of selected interventional Some investigators reported the use of SEPs in 23 embolization
procedures. The most common neuroradiologic procedures sessions performed in 17 patients. 307 In their study, two patients
monitored are carotid artery angioplasty, deliberate arterial oc were unable to undergo embolization because of positive results
clusion of a variety of extracranial and intracranial vessels, coil of the Amy tal testing. In one case, SEPs demonstrated an ampli
ing of intracerebral aneurysms, and in the glue embolization of tude reduction of greater than 50% and the results of the physi
cerebral AVMs. The modalities chosen to monitor such cases cal examination showed a new neurologic deficit after the
depend on the cerebrovascular territory at risk and whether the administration of Amytal; in the other case, only the SEPs were
patient will be awake or under general anesthesia during the used because the embolization was performed under general
procedure. The recordings are performed in a similar fashion to anesthesia. The investigators believed that the combined use of
those described in previous sections. One important exception SEPs and neurologic examination was valuable in the treatment
is in the awake patient, where neurologic examination and su of rolandic AVMs. In a series of 17 patients undergoing balloon
perselective Amytal testing can augment 10M. Amy tal testing occlusion test of the leA due to tumor infiltrate, a combination
consists of injecting a small dose of Amy tal directly in the pedi of clinical, electrophysiologic (median nerve SEPs and trans
cle that is to be embolized or the vessel that is to be occluded. cortical motor evoked potentials), and Doppler sonographic
Chapter 12 INTRAOPERATIVE NEUROPHYSIOLOGIC MONITORING - 465
n ..
. -
r'lr---...----""1
ft ..
~---""'j - ..........-----!'l..-_-"'"
•
A B
Figure 12-29. 14-year-old female with scoliosis and rapid curve progression following spinal ganglioblastoma resection and radiation ther
apy I year prior. 10M of anterior and posterior spinal fusion (T3-L3) with instrumentation was performed.
Traces 1-3: Right cortical SEPs (Cz....fz, Cz'-Fz, and C 3'-C..') after left side stimulation
Trace 4: C-7 (C7-Fz) after left side stimulation
Traces 5-7: Left cortical SEPs (Cz....fz, Cz'-Fz, and c..-C1') after right side stimulation
Trace 8: C-7 (C7-Fz) after right side stimulation
B, Loss of cortical (traces 2-3 and 6-7) and cervical spine-generated SEPs (traces'" and 8) during the placement of the second rod but prior to
distraction. Peripheral (popliteal fossa) recorded EPs are present (traces I and 5), indicating intact peripheral conduction. Scalp-recorded median
nerve SEPs (not shown) were unchanged from baseline. These findings are consistent with acute cord injury.AII spinal hardware was removed as a
result of the SEP changes and wake-up test was equivocal. Unfortunately, the patient developed postoperative severe paraparesis and lower ex
tremity sensory loss. After several weeks, she began to regain sensation and leg strength.
monitoring was used to detect severe cerebral complications.19 been used. The first technique employed was the intraoperative
These investigators concluded that neurophysiologic monitor wake-up test,21,412 The so-called wake-up test is simple; anes
ing played an important role in predicting cerebral complica thesia is discontinued at a critical stage during surgery (usually
tions after permanent occlusion of the ICA (Fig. 12-28). after distraction/derotation), and patients are asked to wiggle
In addition to EPs, EEG has also been used in cerebral and their toes. Unfortunately, the wake-up test has severallimita
carotid balloon test occlusion. In one study, continuous poly tions. It requires a cooperative patient who can comprehend,
graph and quantitative EEG were used along with repeated hear, and follow simple commands; requires presurgical re
detailed clinical examinations in 17 cases. 57 Four of 17 con hearsal; interrupts the surgical procedure; can take up to 15 min
secutive patients showed changes in either their EEG or their utes or more to complete, which means it may occur up to 20
clinical examinations during carotid occlusion. The authors minutes after the spinal distraction; and may fail to detect spinal
concluded that continuous EEG monitoring and repeated clin cord injury.78.282It is not without hazards, which may include ac
ical examinations provide useful ways of evaluating cerebral cidental extubation, vascular line interruptions, air embolisms,
circulation during carotid test occlusions. In a separate study, and dislodging the spinal instrumentation just placed, and some
the EEG was used to monitor 19 patients during cyanoacry patients may not be able to cooperate adequately.94.18o.282
late AVM embolization. 302 Focal or diffuse EEG abnormali Furthermore, the wake-up test provides only a one-time neuro
ties in the lower frequency range could be followed by logic assessment and does not allow continuous monitoring.
clinical hazards (3 out of 1] cases). Theoretically, it is possible that by the time the wake-up test is
performed, damage to the spinal cord has already occurred and
SPINAL SURGERY may be irreversible. This subsequently has led to the use of elec
trophysiologic techniques that would allow continuous monitor
The main use of 10M where the spinal cord is at risk involves ing of spinal cord function. ll2• Different strategies in stimulation
scoliosis surgery. However, some authors believe 10M should and recordings have been used; typically peripheral nerve or
be used in any patient who is at risk for injury to the spinal cord spinal epidural stimulation is performed, and recordings are ob
during any surgical procedure. 101 ,275 tained from epidural, interspinous ligaments, spinous process,
or scalp sites. 229 ,377 The most commonly used methods are the
Scoliosis Surgery spinal evoked potential (recorded from the skin, interspinous
The risk of postoperative paraplegia and paraparesis as a ligament, vertebrae, or epidural space) and the scalp-recorded
result of instrumentation procedures for scoliosis correction has SEP. Generally, tibial or peroneal nerve SEPs are used to moni
been reported to be 0.72%.230 Spinal cord injury may result from tor below the C8 level, and median or ulnar nerve SEPs are per
several factors, including compression or traction of the cord, formed to monitor above the C8 leve1. 159 The criteria for SEP
intraoperative vascular insufficiency, and trauma.99 With this in compromise is a 50% amplitude reduction or >5 ms latency
mind, several methods of monitoring spinal cord function have shift sustained for greater than 10 minutes. 376 Although SEPs do
466 - PART II BASIC AND ADVANCED TECHNIQUES
not monitor the central motor pathways, animal studies suggest PERIPHERAL NERVE SURGERIES
that SEPs are sensitive to acute spinal cord damage from either
ischemic or mechanical insults to the spinal cord (Fig. 12-29).324 Peripheral nerve surgery can be monitored with intraoperative
Several studies have demonstrated the validity of SEP moni neurophysiologic techniques, especially NCS. EMG, and SEP
toring in scoliosis surgery.94.282.288 A large multicenter survey as techniques.191.192.291.314.357.358 This monitoring has been successfully
sessed surgical outcome from centers that use SEP monitoring implemented with the benefits of helping to guide dissection,
in scoliosis surgery, obtaining data on 51,263 procedures, and identify neural structures, and evaluate for traction or vascular
found that experienced SEP monitoring teams had fewer neuro compromise. 175 •188-190.202.291.293.317.357.384.405.429 Typical procedures
logic deficits and that false-negatives occurred in only 0.063% that call for such monitoring are neurolysis, nerve grafting after
of patients. 288 The investigators recognized that intraoperative traumatic nerve injuries, excision of tumors that encroach upon or
intervention (secondary to SEP changes) may have prevented or encase nerves, resection of cysts, and nerve releases or transposi
reduced the severity of any postoperative deficit, thereby influ tions. Also surgical reexploration of scarred areas where anatomy
encing the outcome and artificially raising the number of false can be difficult to identify and the scar itself can be contributing
positive cases and undercounting true-positive cases. With this to nerve compromise and any procedure that may lead to acute
assumption, sensitivity and specificity of SEP monitoring were nerve traction or stretch such as total joint arthroplasties or joint
calculated as 92% and 98.9%, respectively. They also found a contracture releases warrant monitoring.
negative predictive value of 99.33% but only a mediocre posi Spontaneous EMG monitoring of more distally innervated
tive predictive value of 42%. They concluded that SEP monitor muscles can help to detect nerve irritation or stimulation, alert
ing detects more than 90% of the intraoperative neurologic ing a physician as to the proximity to those nerves. This is very
deficits and that SEP monitoring for scoliosis surgery is a clini similar to the techniques described above for posterior fossa
cally useful, valid procedure. tumor explorations. Additionally, triggered EMG can be used
wherein the surgeon stimulates suspected tissue and evaluates
Other Spinal Surgeries which monitored muscles become activated by that stimulation.
The use of SEPs as a measure of spinal cord function is not This is a variant of nerve conduction studies in which the mus
limited solely to scoliosis surgery. It has also been found useful cles may be studied by surface electrodes, though more often by
in other spinal surgical procedures such as spinal AVMs and intramuscular electrodes to optimize isolation of each specific
tumors, unstable fractures, resection of syringomyelia, spinal muscle. With intramuscular electrodes, free-running sponta
decompression, embolization of spinal AVMs, and in children neous EMG activity, triggered EMG data, or both can be de
undergoing selective dorsal rhizotomy.99.311.371 Nash and rived and monitored simultaneously during a procedure.
Brown 275 stated that "it is standard practice to conduct some Examples of some complex setups that can be used include
form of monitoring when performing any spinal operation that (l) brachial plexus: serratus anterior, rhomboid, supra
is associated with a high risk of neurological injury. Generally, spinatus/infraspinatus, deltoid, biceps, brachii, triceps, wrist ex
operations are considered to carry such a risk when corrective tensors, wrist flexors, thenar eminence, hypothenar eminence,
forces are being applied to the spine, the patient has pre-existing first dorsal interosseous; or from the lower limb: (2) sciatic
neurological damage, the cord is being invaded, or an os nerve: biceps femoris, peroneal component-tibialis anterior,
teotomy or other procedure is being carried out in immediate peroneus longus, extensor digitorum brevis-and tibial compo
juxtaposition to the spinal cord." In spite of the impressive track nent-gastrocnemius. 358
record of SEPs in monitoring spinal cord function. false-nega Nerve conduction studies can be used with intraoperative
tive cases have been reported and are of concern.99•288 The criti field stimulation of the nerves being explored or from stimula
cism of mixed nerve SEP spinal cord monitoring is that it tion of the nerve outside the operative field. This requires pre
measures conduction in the ascending sensory pathways located operative setup and baseline testing. If muscle relaxants can be
in the posterior columns while the anterior, motor pathways avoided, by adequate alternative anesthesia regimens, intraoper
remain unmonitored. Thus. several techniques have evolved in ative CMAP monitoring can be used. CMAPs have significant
an attempt to monitor the spinal cord motor pathways. intraoperative advantages, owing to the CMAP amplitude being
Motor evoked potentials (MEPs) can be generated by apply at least two orders of magnitude (100 times) greater than nerve
ing an electrical or magnetic stimulation transcranially to the action potentials' (NAPs) amplitudes. This feature makes
motor cortex or to the spinal cord and recording distal to the CMAP recordings easier to obtain and more resistant to the dis
spinal level of interest from the spinal cord, peripheral nerve, or torting effects of the high levels of electrical noise common to
muscle.42.160.181.217 Unfortunately, the clinical utility of MEPs is the operating room environment than are the much lower ampli
limited owing to the effect of anesthetic agents on the motor tude NAPs. However, if muscle relaxants are used, averaged
pathways, causing severe reduction of MEP amplitude. NAP amplitudes may be more reliable than the more easily
However, different anesthetic techniques are currently being in recorded CMAPs which change amplitude in response to the
vestigated that may facilitate recording of MEPs in the operat muscle blocking agent, and thereby, compound interpretation of
ing room. Transcranial electrical and magnetic stimulation is any changes in amplitude. Peripheral nerves, however, are sen
still considered experimental in the United States, and the de sitive to core body temperature changes, which can significantly
vices are not approved by the Food and Drug Administration. alter the peripheral nerve's conduction latencies and amplitudes.
Certain centers use direct spinal cord stimulation with record Because of this, any changes detected in latency or amplitude
ings obtained from the lower extremities using either surface or measured along peripheral nerve paths require obtaining the
intramuscular EMG recordings to assess the motor pathways. concurrent core body temperature to assist in interpreting
However, this technique can be technically challenging to the whether such changes are physiologic and expected, or herald a
neurophysiologist and anesthesiologist because the patient potential nerve compromise. Surface CMAPs or NAPs correlate
cannot be completely paralyzed and the level of neuromuscular wen to the number of functioning axons, making these useful
blockade must be kept constant throughout the procedure. for quantifying the degree of compromise. When the peripheral
Chapter 12 INTRAOPERATIVE NEUROPHYSIOLOGIC MONITORING - 467
5rnv~
the median, axillary, radial, and musculocutaneous nerves
POSItion ~ D msec.
~ ~::
SEP techniques incorporated for other purposes. 19 Surgical ex
ploration of the mid-forearm median nerve has been described,
.2----~:::
*3 - - - - / / \ ~~ 710
using SEP, and NCS stimulating within the operative field while
recording both outside and within the field. 358
IDp Surgery Sciatic Nerve Monitoring. Total hip arthroplasty
+4 - - - - //\~ 695
can result in compromise of the sciatic nerve, especially the per
2~O~~'O~~'!'>---_/ ~6a5
oneal portion, reported in 0.6-3.5% of cases, with almost twice that
11 LOlency
(msec) incidence after arthroplasty revision surgeries. 113.381 Table 12-15
lists some of the many potential causes of neural compromise that
Figure 12-32. Example of CHAPs in a control subject. They have been reported specifically with hip arthroplasty; however, this
were recorded from the abductor digiti quinti in response to sequen list includes common causes to be considered in many surgical pro
tial stimulation over I-cm segments of the ulnar nerve. The medial epi cedures. m In an attempt to decrease this, both NCS175·182 and SEP
condyle (ME) is considered the 0 point. and stimulation progresses techniques279.381 have been used to warn of impending compromise
from proximal (-) to distal (+). Note the rather uniform latency so that corrective action can be taken. Multiple muscle spontaneous
changes (0.05-0.25 msec over each segment shown to the left of each EMG monitoring has also been advocated. 358 The criteria for SEP
trace) and the constancy of the evoked potential's waveform. (From compromise is a 50% amplitude reduction or greater than 5 ms la
Campbell ww, Sahni SK. Pridgeon RM. Leshner RT: Intraoperative tency shift sustained for greater than 10 minutes. 376 For significant
electroneurography management of ulnar neuropathy at the elbow. NCS criteria to warrant operative changes, an evoked amplitude
Muscle Nerve 1988:1 1:75-81 ,with permission.) decrement of 75% was found to better predict those at increased
risk of compromise. No hip arthroplasty patients having decre
ments less than 75% of their baseline evoked potentials developed
5%, most often to the C8ffl roots, lower trunk, or medial cord, postoperative causalgic symptoms, yet 50% of those with greater
presumably from stretch or retractor pressure.145.153,21O,316,349 than 75% decrements complained of such symptoms postopera
Some advocate the routine monitoring of the brachial plexus in tively (Figs. 12-34 and 12-35).182
other non-brachial plexus related surgeries to avoid deficits Lower Limb Peripheral Nerve Monitoring. During in
from prolonged intraoperative positioning of the arm. 10,236.346 guinal hernia repair the ilioinguinal nerve can be placed at risk,
Upper Limb Peripheral Nerve Monitoring. Arthroplasty and monitoring techniques can help with its identification and
and even arthroscopy has also been associated with peripheral preservation. 358 Monitoring of the peroneal nerve during knee
nerve injuries. 294,373 This has lead to the successful monitoring of surgery has also been described. 429
-------r;~
r/'\'----
'____
10.40 Retraction
rA
10.00
Compression
"--..-- 9.90 Hemorrhage
-----/-'A "----- 9.10
'------riME
-I 0
~8.40
,t-'/"_..' - - - - - - - - - 7.00
Hematoma
Excessive leg lengthening
I
.,----~~ ~ '__ 690 Release of contractu res
::======-=--r~ :::
2.':::0---'---:-'1.0~""""''''·4 ----'r'
'----- 6.60
Penetrating injuries
Ischemia
Patient pOSitioning
t;. LOlency
(msecl
Surgical dissection
Fixation of components
more dispersed than that of response to distal stimulation. Patient un· Reduction maneuvers
ment of ulnar neuropathy at the elbow. Muscle Nerve 1988:11:75-81, From Goldberg G, Goldstein H:AAEM case report 32: Nerve injury associated
with permission.) with hip arthroplasty. Muscle Nerve 1998:21:519-527. with permission.
Chapter 12 INTRAOPERATIVE NEUROPHYSIOLOGIC MONITORING - 469
Stimulation
SEPs are recorded after bilateral independent median nerve Table 12-16. A Method of Placing Electroencephalograph
stimulation using standard bipolar bar surface or subdermal Electrodes by the International Ten-Twenty System
needle electrodes at the wrist Stimulation is at a rate of 3-5 Hz I. Measure the distance from the nasion to the inion and make a
with a 0.1-0.3 msec pulse duration and a constant current inten mark at SO% of this distance.
Fp I on the left and Fp2 on the right.Also mark 10% of this dis
02 on the right.
7. Mark half the distance from T3 to Fp I for F7. Repeat on the right
for the location of FB.
B. Mark half the distance from T3 to 0 I for TS. Repeat on the right
for the location ofT6.
9. Mark half the distance from Cz to T3 for C3. Repeat on the right
for the location of C4.
10. Mark half the distance from Cz to Fp for Fz. Mark half the dis
tance from Cz to Oz for Pz.
I I. Mark half the distance from C3 to Fp I for F3. Mark half the dis
tance from C3 to 01 for P3. Repeat for the right side of the head
for F4 and P4.
12. Primes indicate 2 cm posterior (toward the OCCiput) to the above
points, e.g., C3' and C4' are 2 cm horizontally more occipital than
C3 and C4 derived as above.
Figure '2-35. Recording hook electrode around exposed sci
From Schwentker Me, Forney DJ, Gieski R,Winters JI: Technical standards and
atic nerve. (From Kennedy WF, Byrne TF, Majid HA. Pavlak LL.: Sciatic techniques for basic electroencephalography. In Russell GB, Rodichok LD (eds):
nerve monitoring during revision total hip arthroplasty. Clin Orthop Primer of Intraoperative Monitoring. Boston. Butterworth-Heinemann. 1995, p
1991 ;264:223-227, with permission.) 56, with permission.
470 - PART II BASIC AND ADVANCED TECHNIQUES
CZ'-FZ
Recording
C7-FZ
The pickup electrodes can be placed outside the operative
Ipsilateral popliteal fossa-knee reference
field, in which case usual surface electrodes are most often
used, well secured to prevent being dislodged during surgeon
BAEPs and staff incidental contact and pressure. If identification of ex
EEG scalp electrodes are prepared in a similar manner as actly which branch is required, occasionally the pickup elec
listed above and electrode impedance maintained below 5 kohm. trode will be an intramuscular wire (see below). These wires
Stimulation is by ipsilateral alternating compression and rarefac al10w very precise localization of which nerve portion was stim
tion clicks at 90 dB HL of 100 /ls duration at 20 Hz rate with 70 ulated but do not permit the quantification of nerve or muscle
bB contralateral wideband pseudorandom masking noise. evoked response decrement that surface electrodes can perform.
Electrodes are placed in the vertex region at CZ and CZ' and on Intraoperative field electrodes, typically sterile hooks or special
both ears (AI and A2). Low filter is set at 150 Hz, and the bigh forceps, can be used to either stimulate or pick up a nerve or
filter at 3 kHz. Typically at least 1000 averages are required. 343 muscle response within the field of dissection. The nearer the
electrode is to the stimulated tissue, the larger the response ex
EEG pected. Averaging may not be required for near-nerve record
Usually all scalp electrodes are applied and held securely with ings but usually will be required for surface nerve evoked
collodion. Electrode impedance is maintained below 5 kohm. A potential recordings. Triggered EMG and motor evoked poten
bipolar anteroposterior 16-channel montage covering the tial recordings often do not require averaging, but multiple trials
parasagittal and temporal regions provides adequate evaluation are necessary to confirm results.
Chapter 12 INTRAOPERATIVE NEUROPHYSIOLOGIC MONITORING - 471
INTRAOPERATIVE EMG TECHNIQUES 2, Adams DC, Emerson RG: Intraoperative spinal cord monitoring. Curt Opin
Anaesthesioll996;9:37l-375,
3. Agnew WF, McCreery DB: Considerations for safety in the use of exlIacranial
Recording intraoperative isolated muscle EMG signals requires stimulation for motor evoked potentials, Neurosurgery 1987;20:143-147.
initially placing intramuscular fine wires (O.03-mm insulated 4. Ahn S. Jordan SEt Nuwer MR. et al: Computed electroencephalographic topo
nickel-chromium wires with hooked 3-mrn bared tips) into target graphic brain mapping: a new and accurate monitor of cerebral circulation and
function for patients having carotid endarterectomy. J vase Surg \988;8:247-254.
muscles through a 26-gauge needle preoperatively.378 These leads 5. Albanese SA, Spadaro JA. Lubicky JP, Henderson NA: Somatosensory cortical
are then secured so that incidental pressure does not pull out the evoked potential changes after deformity correction, Spine 1991;16(suppl):
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6. Allen GC: Assessing and responding to detected abnormalities during intraop
on the percutaneous leads. The muscle sites examined are usually erative neurophysiologic monitoring. In: Russell GB, Rodichok LD (eds):
outside the surgical area and thus not within the dissection field. Primer of Intraoperative Monitoring, Boston, Butterworth-Heinemann,I995, pp
With these electrodes, spontaneous free running EMG signals can 245-259.
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evoked potentials during carotid endarterectomy. J Neurol 1992;239:241-247,
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be used to record stimulated responses in triggered EMG mode, to ogy. Neurology 1990;40:1644-1646.
assist with dissection or nerve branch identification. 358 9. American Electroencephalographic Society: Guideline Eleven: Guidelines for
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10. Anderson SK, Loughnan BA, Hetreed MA: A technique for monitoring evoked
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ment with increasing acceptance and demand, which requires the 12. Angel A, leBeau F: A comparison of the effects of propofol with other anaes
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Scoliosis Research Society issued a position statement that intra 8:51-57,
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16. Baba H. Tomita K, Umeda S. et al: Clinical study of spinal cord evoked poten
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l. EEG, CSA, and SEP in CEA and brain surgeries that po Handbook of Spinal Cord Monitoring. London. Kluwer. 1994. pp 104-109.
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20. Ben-David B. Haller G. Taylor P: Anterior spinal fusion complicated by para
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tially involving ischemia or mechanical trauma of the spinal cord. 1987; 12:536-539,
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promising, MEPs and VEPs are still investigational. 22. Bennett HL, Benson DR: Somatosensory evoked potentials for orthopaedic
spine trauma. J Orthop Trauma 1989;3:11-18.
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24, Bieber E, Tolo V, Uematsu S: Spinal cord monitoring during posterior spinal in
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cord action potential measurement. Int Orthop 1978;2:39-46. 438. Zampella E. Morawetz RB. McDowell HA, et al: The importance of cerebral is
410. Ubags LH. Kalkman CJ. Been HD. Drummond JC: The use of a circumferential chemia during carotid endarterectomy. Neurosurgery 1991 ;29:727-731.
cathode improves amplitude of intraoperative electrical transcranial myogenic 439. Zentner J: Scalp recorded somatosensory evoked potentials in response to cauda
motor evoked responses. Anesth Analg 1996;82: 1011-1 014. equina stimulation in neurosurgical operations on the spinal cord. Br J
411. Van Beek A. Hubble B, Kinkead L. et al: Clinical use of nerve stimulation and Neurosurg 1989;3:39-44.
recording techniques. Plast Recontr Surg 1983;71:225-240. 440. Zentner J: Noninvasive motor evoked potential monitoring during neurosurgical
412. Vauzelle C, Stagnara P. Jouvinroux P: Functional monitoring of spinal cord ac operations on the spinal cord. Neurosurgery 1989; 24:709-712.
tivityduring spinal surgery. Clin Orthop 1973;93:173-178. 441. Zentner J: Motor evoked potential monitoring during neurosurgical operations
413. Veilleux M, Daube JR, Cucchiara RF: Monitoring of cortical evoked potentials on the spinal cord. Neurosurg Rev 1991; 14:29-36.
during surgical procedures on the cervical spine. Mayo Clin Proc 1987 ;62: 442. Zentner J, Albrecht T. Heuser D: Influence of halothane, enflurane, and isoflu
256-264. mne on motor evoked potentials. Neurosurgery 1992;31:298-305.
Chapter 13
Chemical Denervation
Botulinum Neurotoxins: Physiology and The Role of Needle EMG and Electrical Stimulation In
Pharmacology BTXTherapy
Structure and Activation • Cell Intoxication Technique
• Presynaptic Neurophysiologic Effects • Postsynaptic
Therapeutic Uses of Botulinum Toxin in Specific
Effects • Other Possible Effects • Autonomic Nervous
Disorders
System Effects
Cervical Dystonia • Spasmodic Dysphonia • Voice Tremor and
Stuttering • Cricopharyngeal Dysphagia • Blepharospasm
Commercial Preparations • Hemifacial Spasm • Oromandibular Dystonia • Limb Dys
Pharmacology of Commercially Available Botulinum Toxin tonia • Nondystonic Tremor • Spasticity • Detrusor-Sphincter
• Resistance and Antibody Production • Contraindications Dyssynergia • Gastrointestinal Disorders • Hyperfunctional
and Side Effects • Toxicity Facial Lines • Hyperhidrosis • Illustrative Case
Chemical denervation using botulinum toxin (BTX) has revo junction, but it also inhibits ACh release from pre- and postgan
lutionized treatment for many disorders with excessive muscle glionic nerve endings of the autonomic nervous system. 45 These
activity in common. These conditions include movement disor sites of toxin activity predict the potential indications and side
ders such as dystonia and tremor; spasticity in multiple sclero effect profiles of BTX as a therapeutic agent.
sis, cerebral palsy or stroke; and disorders of ocular motility, BTX-A is commercially produced and has been FDA-ap
including strabismus and nystagmus. There is a preliminary proved for human use in the United States since 1984.197 BTX
body of literature describing the use of BTX in pain syndromes. B is now commercially available.
including fibromyalgia and headache. BTX blocks the release
of the neurotransmitter acetycholine (ACh) from autonomic STRUCTURE AND ACTIVATION
nerve terminals as well as from the neuromuscular junction. and
is being used in novel ways to modulate autonomic functions Clostridial neurotoxins are synthesized as a single inactive
such as excessive or pathologic sweating or gastrointestinal dys 150 kDa polypeptide chain released by bacterial lysis. Bacterial
motility. or tissue proteases cleave this polypeptide into active neurotox
ins consisting of one heavy (H) 100 kDa chain and one light (L)
50 kDa chain (Fig. 13-1). BTX folds into three functionally dis
PHYSIOLOGY AND PHARMACOLOGY OF tinct domains. The carboxy-terminus of the H chain binds to
BOTULINUM NEUROTOXINS neuronal cells. The amino-tenninus of the H chain is implicated
in membrane translocation. The L chain is a zinc-endopeptidase
The bacterium Clostridium botulinum produces seven differ responsible for intracellular toxic activity. The H and L chains
ent serotypes of toxin (A. B. C, D, E, F, and 0). These serotypes are held together by an inter-chain disulfide bond. 54,148,199.218
are antigenically distinct, but have a common subunit struc Reduction of this bond inside the neuronal cell activates the L
ture. l92 Serotypes A, B, and E are linked to most cases of botu chain to express its zinc-endopeptidase activity. 148
lism in humans. Food-borne botulism is caused by ingestion of
undercooked food contaminated by neurotoxin-producing anaer CELL INTOXICATION
obic spores of Clostridium botulinum. Spores generated in
anaerobic sections of the newborn intestine cause infant botu There is a four-step process for cell intoxication by BTX: (1)
lism. BTX C has been cultured from wounds in patients with cell binding, (2) internalization, (3) membrane translocation,
wound botulism. 142 These toxins bind to nerve cells and enter the and (4) target modification in the cytosol. 14l1 BTX receptors are
cytosol to interfere with nerve transmission by blocking the exo located on the motor neuron plasmalemma at the neuromuscu
cytotic release of ACh. BTX is most potent at the neuromuscular lar junction. Oangliosides, gangliolipids containing sialic acid
479
480 - PART II BASIC AND ADVANCED TECHNIQUES
......
III..srtClflC .....
'_lOCAl...
that precedes the onset of nerve transmission blockade. During
this period the toxin is screened from the action of anti-toxin,
and internalization of the toxin by receptor-mediated endocyto
sis occurs.193 BTX inaccessibility to anti-toxin has a half-time
of approximately 5 minutes, an order of magnitude greater than
the rate at which transmission fails. This difference suggests
the presence of an intervening step between translocation
across the nerve membrane and the final lytic step resulting in
H H paralysis. In After internalization, the L chain packaged in en
'd dosomes must be moved across the endosome membrane into
the cytosol. The amino-terminus of the H chain is thought to
form transmembrane ion channels at an acidic pH allowing for
passage of the L chain and at least part of the H chain into the
cytosplasm.1 6,7S.IOS,179,188
The apparatus mediating exocytosis in the motor nerve termi
nal consists of several protein components. The toxic intracellu
lar activity of BTX is mediated by zinc-dependent specific
proteases targeting components of this apparatus. Different
FIGURE 13-1. Structure-function relationships in clostridial
BTX serotypes cleave the different components (Fig. 13-2).
neurotoxins. The 50-kDa carboxy-terminal domain of the H-chain is
BTX B, D, F, and G specifically recognize and cleave vesicle
mainly responsible for specific binding to receptors on the presynaptic
associated membrane protein (VAMP)/synapatobrevin.
membrane (top left panel). Binding is followed by internalization of the
BTX-A and E cause specific hydrolysis of SNAP·25 (synapto
toxin-receptor complex inside vesicles. The amino-terminal domain of
somal-associated protein of 25 kDa). BTX-C cleaves syn
the H-chain is thought to be involved in the membrane translocation
taxin. 148 BTX does not cleave the short polypeptides containing
of the L chain into the cytoplasm (top right).The L chain is freed in the
the cleavage site of the target proteins. Only long polypeptides
cytosol by the reduction of the interchain disulfide bond and can dis
are cleaved, suggesting that the proteases recognize other seg
play zinc-endopeptidase activity (lower panel). (From Montecucco C,
ments and/or require a specific amino acid conformation in the
Schiavo G: Mechanisms of action of tetanus and botulinum neurotox
vicinity of the cleavage site that occurs only in larger polypep
ins. Mol Microbiol 1994; I 3: 1-8, with permission.)
tides (Table 13-1). J89
From Brin MF: Botulinum toxin: Chemistry. pharmacology. toxicity. and immunology. Muscle Nerve I997;20:S 146-S 168. with permission.
fibers possessing multiple endplates that may be innervated by turns/amplitude ratio both increase after injection with BTX on
more than one axon.l The nodal and terminal axon sprouts may quantitiative electromyography (EMG).77
be present for as long as 3 years following therapeutic use of
BTX-A.l06 This axonal sprouting can be prevented by direct OTHER POSSIBLE EFFECTS
electrical stimulation of the muscle supplied by the BTX-ex
posed nerve. 34 There is no question that BTX presynaptically blocks ACh
release at the neuromuscular junction; however, some clinical
POSTSYNAPTIC EFFECTS observations pertaining to therapeutic use of BTX for dystonia
are difficult to explain by BTX action at presynaptic motor ter
Cholinergic transmission exerts trophic effects on striated minals alone. Clinical benefit following intramuscular injection
muscle and is necessary for normal muscle enzymatic activity is delayed by several days and increases over a period of weeks
and differentiation. Enzymes of energy metabolism are de while a decrease in MEPPs can be demonstrated within a few
creased in BTX-treated muscle. Visually, the muscle size and hours. l62 Dystonic spasms are reduced in both frequency and
the color difference between slow and fast muscles become less strength following treatment with BTX. Clinical weakness cor
apparent. 39.60 Type I (slow-twitch) fibers are characteristically relates only poorly with improvement in dystonic activity and
rich in succinate dehydrogenase and poor in phosphorylase.
Type II (fast-twitch) fibers stain stongly for phosphorylase and
weakly for succinate dehydrogenase.s7.'29
Histochemically, after injection with BTX, each type of fiber
shows a greater decrease in the enzyme activity normally pre
dominant in that fiber type. Atrophy involves all fiber types, but
is faster in onset and recovery in predominantly type I mus
cles.64.65.194 Light and electron-microscopy show reversible
changes in all fiber types. These changes include myofilament
loss with reduction in cross-sectional area, dense body forma
tion, lysosome accumulation, and formation of parallel tubule
clusters of sarcoplasmic reticulum origin. Levels of ACh at the
NMJ fall by 50-63% following BTX administration.6l.202 A
comparision study ofthe histologic appearance of orbicularis
oculi muscle from myectomized blepharospasm patients treated
with BTX to orbicularis oculi muscle from untreated patients
found no consistent, long-lasting alterations in muscle fiber
morphology.97
Electrophysiologically single-fiber studies show increased FIGURE 13-3. Axonal sprouting after BTX. Some sprouts (S)
jitter and blocking that is less marked with higher rates of motor from the preterminal axon (PTA) end in small dilations, presumed to
unit discharge. 176 Abnormalities in jitter can be demonstrated in be the growth cone of the axon. in a muscle after 9 BTX injections (x
muscles distant to those injected even with the small doses used 250. SCI using an antibody to PO). (From Borodic GE, Ferrante RJ.
for the treatment of hemifacial spasm. 8S Fibrillations and posi Pearce LB, Alderson K: Pharmacology and histology of botulinum
tive sharp waves similar to those seen following surgical dener toxin. In Jankovic J. Hallett M (eds):Therapy with Botulinum Toxin. New
vation are seen in muscles injected with BTX.l68 Turns and the York, Marcel Dekker. 1994, pp 119-157, with permission.)
J82 - PART II BASIC AND ADVANCED TECHNIQUES
Jinical benefit may persist for weeks or months after the reso hemifacial spasm demonstrated mild abnormalities of cardio
,ution of localized weakness. 83 These observations have vascular reflexes as a distant effect. 85
Jfompted investigators to hypothesize that alteration in afferent
nput mediated peripherally by BTX results in secondary cen
ral reorganization. 37,83,84 COMMERCIAL PREPARATIONS
BTX has direct effects on the intrafusal fibers of gamma mo
orneurons in muscle spindles. 74 ,m Physiologic changes have PHARMACOLOGY OF COMMERCIALLY AVAILABLE
)een described in the spinally mediated reciprocal inhibition of BOTULINUM TOXIN
?atients with arm dystonia treated with BTX.167 Patients with
Ipper limb dystonia demonstrate a decreased second phase of Dr, Hermann Somner first attempted to purify BTX-A in the
eciprocal inhibition as studied by conditioning the H-reflex in 1920s, but Dr, Carl Lammanna first chrystallized BTX-A bind
'orearm flexors with a radial nerve stimulus, Treatment with ing toxic units to nontoxic proteins in 1946,197 The 900-kD
3TX increased the second phase of reciprocal inhibition, There chrystallized form of BTX is used therapeutically today, This
Nas no change in the initial phase of reciprocal inhibition, form includes both the neurotoxin and nontoxic proteins, some
Nhich is normal compared to controls, The authors suggest that of which agglutinate red blood cells (hemagglutinins), Only
his concurrent indirect effect of spinal inhibition may be medi 20% of the protein in the chrystalline preparation is neuro
lted through the effect of BTX on the intrafusal neuromuscular toxic. 53 The toxin is produced through a process of anaerobic
unction, More recent work with repetitive transcortical mag fermentation under highly controlled conditions, Botox, a com
letic stimulation of the motor cortex has demonstrated that the mercially produced BTX-A product is FDA-approved for use in
ntracortical deficiency in inhibition seen in dystonia is also the United States, It is derived from the Hall strain of
xansiently normalized following treatment with BTX,37,84 Clostridium botulinum in medium containing yeast and N-Z
The amplitude of the precentral P221N30 median somatosen amine. 128 Toxin is precpitated and harvested by centrifugation,
iory evoked potential in frontal electrodes contralateral to the Crude toxin is purified by sequential precipitation and ion-ex
lirection of head movement is significantly higher than in change chromatography. The product is periodically assayed for
,'rontal electrodes ipsilateral to the direction of head movement toxin activity and purity and is ultimately mixed with serum al
n patients with cervical dystonia, This side-to-side amplitude bumin and lyophilized. 86 Lyophylization and filtration cause
jifference is not found in normal subjects. 113,1 14 Like motor dis some damage to the toxin structure, reducing the toxicity of the
,nhibition, these somatosensory evoked potential abnormalities final commercial product. 177
,n patients with cervical dystonia normalize after treatment with Differences in production methods account for the differ
BTX. The reduction in the contralateral P221N30 may reflect ences in activity and weight of BTX produced by different com
the change in the direction of head rotation, and the pattern and panies. Dysport is the BTX-A product produced commercially
force of muscle contraction after treatment, but a reduction in in the United Kingdom. The unit of measurement for BTX is
.be abnormally high level of excitability of cortex by treatment the mouse unit (U). This is a unit of potency determined by
with BTX cannot be excluded. 114 mouse assay according to published specifications. One unit of
Some animal studies suggest that intramuscularly injected BTX-A is equal to the amount of toxin that will kill 50% of a
BTX can reach the CNS. Iodine-labeled BTX-A injected into the group of 18-20 female Swiss-Webster mice. 29,98 A vial of Botox
gastrocnemius muscle of a cat produced histologic evidence of contains 100 U. A vial of Dysport contains 500 U. By definition
lccumulated radioactivity in the ipsilateral spinal cord 3-4 days it would follow that one unit of Botox and one unit of Dysport
following injection, suggesting retrograde axonal transport of should have equivalent clinical effect; however, Botox contains
the toxin takes place. 210 Despite the finding that BTX is bound greater quantities of detoxified toxin than Dysport.177 As a result
by synaptosomes in the rat brain, there is at this time no evidence 1 nanogram (ng) of Botox equals 2.5 U whereas 1 ng of Dysport
that BTX has a physiologic effect on the human brain. 15,83,153 equals 40 U.169 Clinically, a bioequivalent ratio of one Botox
unit to three Dysport units has been recommended.I37,155
AUTONOMIC NERVOUS SYSTEM EFFECTS In 1997 the FDA approved a new neurotoxin complex pre
pared from a new bulk toxin source. This toxin has less toxicity
Autonomic symptoms are also characteristic of clinical botu by weight per biologically active unit than the original Botox.
lism, Autonomic symptoms include constipation, nausea, vom The decreased neurotoxin protein per effective dose appears to
iting, abdominal cramps, heartburn, blurred vision, dry mouth, produce a similar dose-related weakness with decreased neu
micturational disturbance, and sexual dysfunction,IIO In the au tralizing antibody formation tested in an animal mode1. 4 This
tonomic nervous system BTX blocks ganglionic nerve endings, may have important implications for recommended dosing para
post-ganglionic parasympathetic nerve endings and some post digms targeted at minimizing risk of immunoresistance.
ganglionic sympathetic nerve endings. 85 ,135,170 A much higher The lyophilized toxin must be reconstituted with preserva
threshold level of electrical stimulation of parasympathetic tive-free sterile saline (Table 13-2). The reconstituted toxin is
nerves (vagus, chorda tympani, nervus erigens, and oculumotor) stable at room temperature for up to 4 hours.86 BTX-A is not
is required to produce a physiologic effect in animals intoxi flammable or volatile, but spills may result in hazardous mists
cated with BTX compared to control animals. 59 BTX blocks or aerosols. Spills may be inactivated by 0.5% hypochlorite so
contraction of isolated guinea pig vas deferens in response to lution. Toxin-containing solutions are also inactivated by heat
hypogastric nerve stimulation and piloerection in the tail skin ing, boiling, or autoclaving to 121°C for 20 minutes.I78BTX-A
obtained from cats, 170 These responses were restored with direct was approved by the FDA in the United States for treatment of
introduction of noradrenaline, There is experimental evidence strabismus, blepharospasm, and hemifacial spasm in 1989. 30,127
in animals that BTX may additionally block nonadrenergic, at For patients who become resistant to BTX-A an effective, anti
ropine-resistant autonomic neuromuscular transmission in genically distinct alternative serotype could be a welcome alter
some instances,135 Four of five patients injected with BTX for native to phenol injections, rhizotomy, or brain surgery,
Chapter 13 CHEMICAL DENERVATION - 483
TABLE 13-2. Botox Dilution Table have circulating antibodies than patients who continue to enjoy
ml Normal Salinell 00 U Botox Vial Dilution a good clinical response. 95 ,96 Antibodies to BTX-A do not block
the effects ofBTX-B and vice versa.'51
10 UfO.l ml
There are severa) assays available to detect the presence of
2 5 UfO. I ml antibodies in serum. The in vivo mouse neutralization assay is
4 2.5 UfO. I ml widely used. 29,98 In this regard, BTX-A is titrated with the serum
8 1.25 UfO.! ml of the patient suspected of having antibodies and then injected
into mice. If antibodies are present, they bind to the toxin and
10 I UfO.1 ml
protect the mouse from its lethal effects. If antibodies are
From Botox® package insert, with permission. absent, or present in low quantity, the mouse dies. A positive
mouse assay correlates well with lack of clinical response. A
BTX-B cleaves synaptobrevin, a vesicle-associated mem negative response does not exclude the presence of antibody
brane protein. ISO Unlike BTX-A, the initiation of ACh release levels sufficient to cause human resistance, but insufficient to
by BTX-B is not blocked by aminopyridines, which increase protect the mouse. The mouse assay, therefore, underestimates
impulse-evoked Ca2+ by blocking presynaptic potassium chan the presence of clinically significant immunoresistance. 29
nels. 7 BTX-B is now commercially available in the United Several immunoabsorbent assays have been developed. The cor
States, This liquid preparation must be refrigerated but does relation between these assays and clinical resistance has not
not require reconstitution. 32 The clinical effects are similar to been established. The enzyme-linked immunosorbent assay
those produced by BTX-A, but are shorter-lived. The potency (ELISA) is positive in more than half of all patients treated with
of BTX-B is also determined by mouse assay, As with Botox BTX, including those who are still clinically responsive to treat
and Dysport, the clinical effects of one unit are not equivalent. ment. 190 It is possible that these assays detect antibodies to func
In a double-blind placebo-controlled study BTX-B in doses of tionally unimportant parts of the toxin. Additionally, cross
2500-10,000 U in patients with cervical dystonia produced ef reactivity between type A and B BTX occur in systems using
fects comparable to 150-200 U of BotoX. 127 Patients with and polyclonal antibody reagents. 98
without resistance to BTX-A had similar responses. In a multi It is also possible to clinically assay for BTX activity. In the
center, randomized, double-blind, placebo-controlled clinical frontalis type A test (F-TAT) 15 U of Botox are injected unilat
study of 77 patients resistant to BTX-A, results of treatment erally in the frontalis muscle at 2 sites, If within 2 weeks the pa
with 10,000 U of BTX-B were significantly better than for pa tient is unable to wrinkle the forehead on the injected side, he or
tients receiving placebo. 32 Efficacy was determined by im she is "not resistant." These patients may desire to have the
provement on the Toronto Western Spasmodic Torticollis other frontalis muscle injected subsequently to maintain facial
Rating Scale (TWSTRS) and visual analog scales that assess symmetry. If the injected frontalis muscle moves normally, the
global patient benefit and pain. In this study, the overall esti patient is deemed clinically "resistant."29
mated duration of treatment effect was 12-16 weeks. Clinically There appears to be a correlation between the clinical and
relevant adverse events included dry mouth (17/39) and dys electrodiagnostic results of BTX injection and the antibody
phagia (11139). Dysphagia was self-limited and tolerable in af status of patients suspected of antibody-mediated resistance,
fected study subjects. In a similarly designed study, 109 The amplitude of the peroneal CMAP recorded from the exten
BTX-A-responsive patients were randomized to treatment with sor digitorum brevis (EDB) muscle was determined before and
placebo, 5,000 U BTX-B, or 10,000 U BTX-B. Efficacy signif 3-5 weeks after BTX-A injection with 200 U of Dysport. In
icantly exceeding that of placebo was demonstrated with both serum-positive nonresponders the CMAP amplitude was un
the 5,000 U and 10,000 U doses. Clinical benefit was greater changed 4 weeks post-injection. In serum-negative nonrespon
with the 10,000 U dose. Duration of effect and adverse events ders a marked decrease in the CMAP amplitude occurred,
were similar in the BTX-A responsive study to those seen in indicating that the toxin remained capable of activity at the neu
the BTX-A resistant study.27 BTX-C and BTX-F have also romuscular junction in these patients. The lack of BTX efficacy
been studied as treatments for cervical dystonia.70.91.107 The with regard to the dystonia being treated was likely related to an
clinical effects of BTX-F are not as long-lived as those pro inadequate dose or selection of suboptimal injection sites in
duced by serotype and last approximately 1 month. 29 Peroneal these patients. 1I9 Patients demonstrated to be nonresponsive by
CMAP amplitUdes studied serially over 90 days in study sub clinical assays such as the frontalis or EDB tests may benefit
jects injected in the extensor digitorum brevis muscle (EDB) from an alternate BTX serotype regardless of seronegativity or
with BTX-A and BTX-C showed a similar effect and ampli seropositivity on immunologic assays.
tude profile.7° Short intervals between injections, higher doses, and the anti
genic load per dose appear to be related to an increased risk for
RESISTANCE AND ANTIBODY PRODUCTION development of antibodies. 92 To minimize the risk of immunore
sistance it is recommended that the smallest effective dose be
A small percentage of patients receiving therapeutic BTX used at the longest possible interval. Ideally injections should
become clinically resistant. Injections no longer have clinical be 3 or more months apart, and booster injections (defined as
efficacy and injected muscles do not become weak or develop reinjection within 3 weeks of an injection) should be avoided.
atrophy. Resistance is generally thought to be due to the devel These precautions are of particular importance for doses in
opment of antibodies to the toxin, Antibody-mediated resistance excess of 100 U per session. 29.92 These recommendations have
occurs in 3-10% of patients. 29 Some antibodies are directed been based on clinical experience with the original Botox.
against the toxin, while others are directed against associated Current Botox preparations appear to be less immunogenic, po
nontoxic proteins. Only the antibodies that block the toxic tentially allowing higher doses without subtantial risk of devel
action at the NMJ are important clinica\ly.'09 Patients who have oping resistance. 4 Figure 13-4 outlines an algorithmic approach
lost their clinical response to BTX therapy are more likely to to suspected immunoresistance. Plasma exchange has been used
484 - PART II BASIC AND ADVANCED TECHNIQUES
RevIew reinieCtkm
I velopment Conference determined that the safety of BTX ther
apy during pregnancy and breastfeeding and chronically during
strategy and childhood were unknown. 48 There are insufficient data to con
tlming-modify
injection technique Imllilmenl clude that BTX can be used during pregnancy without any risk
anlmative of adverse outcome. Pregnancy, therefore, remains a relative
if needed and trealmenl
reassess role of strategies contraindication for BTX treatment. BTX injection should also
adjunetiYe therapies be avoided in patients with bleeding disorders, or taking antico
t
agulant medication, because of the possibility of excessive
bleeding or hematoma formation.
Schedule for
fDIIDW-Up
rellSlumenl TOXICITY
Ind conslder.lion
for relnlectlon
Toxic doses of BTX show variation between species.
Extrapolation from animal studies to humans must be accepted
FIGURE. 13-4. Algorithm for evaluation of patients failing to with caution. The lethal dose for humans is unknown.
respond clinically to injection with BTX-A. (From Brin MF: Maximum dosage recommendations for human clinical applica
Botulinum toxin: Chemistry. pharmacology. toxicity. and immunology. tion are based on primate studies. The intravenous and intra
Muscle Nerve 1997;20(SuppI6):SI46--SI68 with permission.) muscular LDso in monkeys is between 38-42 U/kg.I02.186
Extrapolation from this primate data to the 70 kg human sug
sucessfully to restore clinical response to BTX-A in an im gests a human LDso of approximately 3000 U. Most experts rec
munoresistant patient severely disabled by cervical dystonia. 152 ommend a maximum dose of 300-400 U per session and a
Use of an alternative serotype is an additional option. maximum of 400 U over any 3-month period. 29 Limited toxicity
data is available for intramuscularly injected BTX-B. In normal
CONTRAINDICATIONSAND SIDE EFFECTS monkeys, intramuscular doses up to 480 Ulkg total body weight
of BTX-B produced no signs oftoxicity.151
Because of the small quantities of toxin used and its avid
binding to local nerve terminal receptor sites, side effects are
generally local. Like the therapeutic benefit, adverse side effects THE ROLE OF NEEDLE
are temporary. In more than a decade of clinical use, no cases of ELECTROMYOGRAPHY AND ELECTRICAL
anaphylaxis or deaths have been attributed to BTX-A.29 STIMULATION IN BTXTHERAPY
Prospective patients should be prepared for the possibility of
excessive local weakness, the most common side effect of BTX The role of needle EMG in BTX treatment of disorders of ex
therapy. Depending on the injection site, weakness may result in cessive muscle activity has not been clearly established. EMG
functionally significant impairment such as ptosis or dysphagia. was frequently used as an adjunct to the clinical examination
With larger doses of BTX some patients may complain of non when BTX was first used to treat cervical dystonia (CD). EMG
specific malaise, myalgia, or flu-like symptoms. These symp was used both to confirm the pattern of muscle involvement,
toms may occur because some of the BTX can be taken up into and to confirm placement of BTX in targeted muscles. Over
the circulation and have effects on the autonomic nervous time, many experts became comfortable with observation and
system. Generalized pruritus without rash has been infrequently clinical examination alone to select and/or to inject muscles,
reported in patients treated with BTX.68.130 Patients receiving in using EMG only when patients failed to benefit from clinically
jection into the orbicularis oculi for blepharospasm or hemifa targeted injections, or when localization of the muscle was
cial spasm may experience a transient increase in intraocular anatomically difficult In dystonia, selection of muscles for injec
pressure due to toxin-induced effects on local cholinergic au tion is clinically based on a number of factors. Patients may iden
tonomic pathways. 139 Plexopathy or radiculopathy have been tify painful areas likely to be the locus of muscle hyperactivity.
Chapter 13 CHEMICAL DENERVATION - 485
TECHNIQUE
Localization of target muscles using EMG is straightforward.
The needle tip is positioned so that a full recruitment pattern is
seen with activation of the targeted muscle. Motor unit action
potentials (MUAPs) should have normal amplitude and short rise
times making a distinctly crisp sound. It is important to empha
size that the presence of crisp MUAPs indicates only that the
needle tip is in a contracting muscle fascicle, but does not con
firm placement in the targeted muscle. Modulation of the EMG
by active contraction or passive movement of the target muscle
is required. Fibrillation potentials and positive sharp waves will
be seen in previously injected muscle after 10--20 days but are
usually not evident after 3 months. l68 The presence of low-am FIGURE' 3-6. EMG instrument setup with active, reference,
plitude, poorly defined units that fire with a mUffled thump and ground electrodes.
486 - PART II BASIC AND ADVANCED TECHNIQUES
Levator scapulae Transverse processes of C 1-04 Superior angle of the scapula Shoulder and scapular elevation
Scalene complex Transverse processes of C 1-C7 Superior surface of first rib between Ipsilateral tum with anterocollis
the subclavian groove and the rib
tubercle
Longissimus capitis Transverse processes of the lower Mastoid process lateral to splenius Ipsilateral tilt and neck extension
cervical and upper thoracic vertebrae insertion
Semispinalis capitis Lower cervical and upper thoracic Medial part of occiput Ipsilateral tilt and neck extension
vertebrae
From Brin MF: Cervical dystonia-syllabus for treatment of dystonia. Workshop demonstrating the use of botulinum toxin. American Academy of Neurology. New
Orleans, 1999, pp 67-88. with permission.
Chapter 13 CHEMICAL DENERVATION - 487
'H___. _ Splllniwlcapilis
+4c----II_~I~·nltnaljugUlar _ _ _ _ Setlenus
~~_ _ _ T,.peZiuS
lr----"">r- 8tachill
plexus
-=--~-Omohyoid
"""........_ _ CI8Yicle
areas are painful. tight, or uncomfortable. The patient should be or hyperactive based on visible spasm, hypertrophy, or head po
asked to relax and let the head and neck deviate without com sition may be injected. In cases in which desired clinical results
pensation or resistance. The resultant head position. presence or cannot be achieved with muscle selection based on the clinical
absence of tremor, and muscle hypertrophy or apparent overac examination alone, EMG can be used to better define the pattern
tivity should be noted. The patient should be asked to demon of muscle involvement. In 72 patients with rotational torticoUis
strate any maneuver he or she has identified to reduce or stop the on clinical exam, the EMG pattern of involvement looking at
abnormal posture (geste antagonist). or any activities. such as SCM, splenius capitis, and trapezius muscles was variable. 58
writing or reading, that may exacerbate or provoke cervical dys Eight patients demonstrated electrical activity in one muscle, 39
tonia. Finally, the muscles of the neck should be palpated for had involvement of two muscles and 25 had involvement of three
tightness and tenderness. Muscles that are tight, tender, painful, muscles. It is important to reassess the pattern of muscle involve
ment at each injection session as the pattern may change with
BTX injection. 81
The SCM arises from the mastoid process and the lateral half
of the superior nuchal line. The clavicular head inserts onto the
medial third of the clavicle and sternal head inserts onto the
manubrium sterni (Fig. 13-8). Unilateral SCM activation ro
tates the chin to the contralateral side, or tilts the head down
toward the ipsilateral shoulder. Bilateral SCM activation may
propulse the head forward or pull the chin downwards. To
inject the SCM, the superior portion of muscle belly should be
grasped between two fingers. The needle is placed into the pos
terolateral fibers as close to the mastoid process as possible
(Fig. 13-9).
The splenius capitis muscle arises from the mastoid process
and the occipital bone just below the lateral third of the superior .
nuchal line. 3 It extends downward, medially. and posteriorly to
insert into the lower half of the ligamentum nuchae and onto the
spines of the seventh cervical vertebrae and the upper thoracic
vertebrae. Its location is somewhat deep. It may be palpated
posterior to the upper posterior border of the sternocleidomas
toid muscle (Fig. 13-1O). Unilateral activation of the splenius
FIGUR£ 13-9. Site of sternocleidomastoid Injection. Injection capitis muscles rotates the head ipsilaterally and tilts the head
is placed in the posterolateral fibers of the sternocleidomastoid as down toward the ipsilateral shoulder. Bilateral splenius capitis
close to the mastoid process as possible. activation extends the neck and pulls the head posteriorly. The
488 - PART II BASIC AND ADVANCED TECHNIQUES
FIGURE 13.1 I. Site ofsplenius capitis injection. The splenius FIGURE '3-13. Site of trapezius injection. (From Anderson Tl:
Spasmodic torticollis. In Moore P (ed): Handbook of Botulinum Toxin
capitis muscle can be palpated just posterior to the sternocleidomas
Treatment. Oxford, Blackwell Science, 1995, pp 103-130, with permission.)
toid at the apex of the angle between the sternocleidomastoid and
trapezius insertions. The injection is delivered at a depth of 1-2 cm
taking care to avoid the venous plexus that lies deep to the splenius superior SCM may be isolated between two fingers and the
capitis muscle. (From Anderson TJ: Spasmodic torticollis. In Moore P splenius capitis is just posterior and deep to the SCM. The sple
(ed): Handbook of Botulinum Toxin Treatment. Oxford. Blackwell nius muscle can be palpated here in the untreated patient and
Science, 1995, pp 103-130, with permission.) the injection is generally delivered 1-2.5 cm deep at this loca
tion. Care should be taken to avoid the venous plexus that lies
deep to the splenius capitis muscle (Fig. 13-11). 3
The levator scapulae muscle originates superiorly from the
transverse processes of the axis, atlas, and the third and fourth
cervical vertebrae. It inserts on the superior third of the medial
border of the scapulae. It is located behind the SCM muscle in
ferior to the splenius capitis muscle and superior to the scalene
complex. It elevates the ipsilateral shoulder and may contribute
-F--- "~..nl"s capitis
to lateral tilting of the head ipsilaterally. The levator scapulae
muscle is localized for injection inferior to the splenius capitis
muscle and superior to the scalenus complex.3 If hypertrophied
it may be palpable. This muscle may atrophy with serial injec
_ _ _ ......."..u. cefvicls
muscles with wire electodes. 103•132 For injection, patients are is used for percutaneous injection. Reference and ground elec
comfortably placed in a supine position with the neck hyperex trodes are placed on the side of the neck or on the back. After
tended. A 1.5 inch, 27 -gauge hollow Teflon-coated needle electrode cleansing with alcohol and skin infiltration with 2% lidocaine
Phonation Normal
Phonation Laryngeal Dystoma
I .F.I!!E!.: ~
......l..,n.... "Sa...... ir...
Nation.l .....ital
u~.,~. 58.'''''Sa
~
..
I
I .
I
~-- ~--~~--~~~~
l
. f
......lee/Tee. "Sapphir.~
the needle is inserted through the cricothyroid membrane 2-8 but may also result in needle tip displacement. 33 The TA, LeA,
mm to one side of midline (Fig. 13-20). Once through the mem and cricothyroid muscles are continuous with one another and
brane, the needle must be angled sharply superiorly and tun the wide field of the monopolar needle can make it difficult to
nelled submucosally laterally and superiorly toward the inferior determine in which muscle the needle tip is located. 132
fold of the vocal cord (Fig. 13-21). If the needle is in the glottic A technique for TA injection of patients with adductor laryn
space or close to the edge of the fold, phonation will be seen and geal dysphonia without EMG guidance has been described. 90
heard on the EMG monitor as a 100-200 Hz complex waveform. The patient is seated and the neck is palpated to identify the out
The needle should be directed more laterally in this event. If the line of the thyroid and cricoid cartilage. A flexible nasopharyn
needle is too far lateral, vibration of the thyroid cartilage will be goscope may be passed though the nose into the hypopharynx
picked up in the EMG signal. 132 If the needle is placed too inferi after topical anesthesia of the nose and hypopharynx with 2%
orly, the EMG will show increased activity with expiration and lidocaine spray. Toxin is injected transcutaneously through the
at the onset and termination, indicating the placement in the thyroid cartilage into the ipsilateral TA muscle. The needle is
LCA muscle. 132 A crisp MUP interference pattern appears with oriented at a 90 0 angle to the skin of the anterior neck and di
prolonged vowel production and with effort closure of the vocal rected posteriorly in the sagittal plane. The anterior commissure
cords when the needle tip is well-placed in the posterior portion of the vocal cQfd is estimated to be midway between the thyroid
of the TA muscle. There is no predominant pattern with respira notch and the bottom edge of the thyroid cartilage in the mid
tion as the TA motor units fire during inspiration and expira line. The needle is placed 5 mm lateral and 5 mm inferior to this
tion.132 Gentle phonation can confirm correct needle placement. point (Fig. 13-22). Correct depth is determined by sensing the
depth at which the needle passes through the thyroid cartilage to
permit easy injection of toxin. If the needle is in the thyroid car
tilage there will be high resistance to injection because of the
density of cartilage matrix. This resistance eases off as the
needle enters the TA muscle. This method is referred to as the
"touch-point" technique.
Indirect laryngoscopy can be used to inject BTX into the
vocal cord under direct visualization in patients who tolerate pe
rioral procedures without excessive gagging. 79 This approach
does not require EMG localization. The patient holds the tongue
out with a gauze pad while the larynx is visualized with a laryn
geal mirror. The larynx is anesthetized with 1 ml of 4% cocaine
(lidocaine or tetracaine may also be used) dripped onto the mu
cosal surface of the endolarynx. The vocal cord is penetrated on
the superior surface using a laryngeal injector device and BTX
is injected to multiple sites along the anterior-posterior axis.
Proponents of this technique used an initial unilateral dose of
FIGURE 13-21. Patient receiving transcutaneous injection of 2.5 U in 0.1 ml.78 If symptoms persist after 4 days, a patient re
the thyroarytenoid muscle with EMG guidance. ceives 3.0 U in the contralateral vocal cord. Some patients required
Chapter 13 CHEMICAL DENERVATION - 493
a third injection. The total doses used during the initial treat
ment were divided, with half being injected in each vocal cord
for subsequent treatments. Total doses ranged from 2.5 to 8 U
with an average effective dose of 4.5 U. Acoustic evaluation of
phonation involved having patients sustain the vowel "a" sound
at a comfortable intensity and pitch for as long as possible.217
The digitized signal can be evaluated for a number of acoustic
parameters. Twenty-seven patients evaluated before and 1
month following injection showed no change in signal-to-noise
ratio, jitter (frequency perturbation), shimmer (amplitude per
turbation), or standard deviation in fundamental frequency from
pretreatment measures. 79 They did have significant differences
in the timing and distortion percentages of conversational
speech and reading of a standard passage. Abnormal words de
creased by 41%. Words with voice breaks decreased 26%.
Improvements were judged to be present on voice recordings in
SO% of patients. These different techniques have not been di
rectly compared against one another for efficacy.
The PCA muscle is targeted for injection in abductor spas
modic dysphonia. Only one side is injected at a time as bilateral
PCA weakness can compromise inspiration. Reaching this
muscle located on the posterior aspect of the larynx is techni
cally more challenging than TA injection in adductor dysphonia
and may be particularly difficult in muscular or obese patients.
The patient is reclined in a supine postion with the head rotated
laterally away from the side to be injected. The larynx is manu
ally rotated away from the side to be treated. Mter the skin and
FIGURE '3-23. Photograph of injection of the posterior
subcutaneous tissue is infiltrated with 2% lidocaine, a 2.5-3.0
cricoarytenoid muscle with EMG guidance. (From Blitzer A, Brin
inch, IS-gauge, Teflon-coated hoUow needle electrode is intro
MF:The evaluation and management of abductor laryngeal dystonia. In
duced at a point midway between the hyoid bone and the cricoid
JankOViC J, Hallett M (eds):Therapy with Botulinum Toxin. New York,
cartilage, just posterior to the anterior border of the SCM Marcel Dekker. 1994, pp 451--459, with permission.)
muscle. The needle is directed obliquely in an inferior and
medial direction until it reaches the firm posterior wall of the
cricoid cartilage. The needle is then withdrawn slightly into the cases of exertional wheezing or stridor and 15 cases of dyspha
belly of the PCA muscle (Fig. 13-23). The patient is asked to gia. These effects were mild and self-limited, lasting about a
activate the PCA muscle by sniffing or inspiring deeply. A cor week. Tremor severity worsened in some cases after treatment.
responding augmentation of the crisp EMG interference pattern The investigators believe that the visible tremor present before
confirms the location of the needle tip in the PCA muscle. 19.33 treatment was made audible with PCA weakening and in
Unilateral BTX injection of 56 patients with abductor dys creased phonation.
phonia failed to produce significant improvement in 75% of pa
tients.19 If fiberoptic laryngoscopy revealed residual vocal cord VOICE TREMOR AND STUTTERING
abduction following an initial unilateral dose of 3.75 U of
Botox, patients received an additional 2.5-3.75 U on the side Work done at the National Institutes of Health with BTX in
originally injected. If the injected PCA was observed to be par jection into the TA muscle for patients with nondystonic voice
alyzed, small serial doses of 0.625-2.5 U were injected into the tremor and stuttering suggests that voice tremor patients experi
contralateral PCA. No additional injections were given if pa enced perceived benefit and reduction in speech effort of a dura
tients developed stridor or significant narrowing of the space tion comparable to that experienced by patients injected for
between the vocal cords (glottic chink). For patients who have spasmodic dysphonia. BTX injection did not appear to be of
had injection of the PCA muscles bilaterally with narrowing of benefit in the treatment of stuttering.196
the glottic opening and for patients with significant tremor, an
additional 2.5 U were injected into the cricothyroid muscle. In CRICOPHARYNGEAL DYSPHAGIA
these 56 patients, 13 had only 1 PCA injected, 13 patients had
both PCA and both cricothyroid muscles injected, and 9 had a BTX has also been used to treat swallowing disorders re
unilateral type I thyroplasty in addition to BTX injection. On a lated to excess cricopharyngeal muscle activity in seven pa
functional rating scale, the average pretreatment function was tients. Swallowing problems were caused by spasticity,
31 % of normal. The average best post-treatment function was hypertonus, or delayed relaxation of the upper esophageal
70% with an average improvement of 39%. Average pretreat sphincter and were the result of a variety of underlying prob
ment overall severity on a standardized 8-point rating scale was lems, including stroke, cancer resection, and acoustic neu
5. Overall severity post-treatment decreased to an average of 3. roma. BTX was administered under general anesthesia. Five
Patients who had isolated vocal cord spasm did better than pa of 7 patients experienced improvement or resolution of dys
tients with combined dystonias. Patients with tremor or respi phagia. ISI BTX was shown also to help dysphagia related to
ratory dyssynchrony prior to treatment also had a less cricopharyngeus muscle and pharyngoesophageal spasm in
satisfactory response to treatment. Adverse effects included 16 patients following laryngectomy.50·67
494 - PART II BASIC AND ADVANCED TECHNIQUES
FIGURE. , 3-27. Injection points used to treat blepharospasm or hemifacial spasm. Note that lateral injections can affect the ipsilateral
zygomaticus major and minor muscles that are retractors of the nasolabial fold and the lateral angle of the mouth. (From Borodic GE, Ferrante RJ,
Pearce LB. Alderson K: Pharmacology and histology of botulinum toxin. In JankOViC J, Hallett M (eds):Therapy with Botulinum Toxin. New York,
Marcel Dekker, 1994,pp I 19-1 57,with permission.)
496 - PART II BASIC AND ADVANCED TECHNIQUES
percent of patients achieved a functional cure defined as restored by different authors. Effective doses may range from 5 to 25 U
alignment persisting for at least a year after the last BTX injec of Botox per eye in blepharospasm patients. The number of in
tion. Thirty-five percent were discharged because they were sat jections may vary from 4-6 injected sites per eye (Fig. 13-27).
isfied with their alignment or wished to stop treatment. Twenty This variability in technique does not appear to significantly
five percent went on to have surgery as an alternative to BTX affect results. lOS The most common side effect of orbicularis
injections. Thirteen percent had ongoing injections. Five and a oculi injection is the development of ptosis. Ptosis is seen in. ap
half percent had surgery in combination with BTX. Less than proximately 12% of BTX treatments for blepharospasm,68 This
1% refused reinjection. Eighty-nine percent of patients had is usually mild and resolves in 1-2 weeks. If more significant
three or fewer injections. A group followed for long-term, re weakness results in functional disability, lid props or crutches
current treatment received many more injections. can be fitted to eyeglass frames and will allow the patient to see
while waiting for toxin-induced weakness to resolve.72 Other
BLEPHAROSPASM side effects include local discomfort or bruising, diplopia
(2.1 %), most often involving the inferior oblique muscle, that
Idiopathic blepharospasm is a focal dystonia. It can be lies just posterior to the orbital septum, lower facial weakness
asymmetric or even unilateral at onset. It must be distin (0.9%), and dry eyes (2.5%) or excessive tearing (epiphoria)
guished from hemifacial spasm when unilateral. Secondary (3.5%).68 I avoid injection of the medial aspect of the lower lid
blepharospasm may be seen with drugs, Wilson's disease, en to minimize risk of lacrimal pump impairment and to avoid dif
cephalitis, and Parkinson's disease. lo8 Pharmacologic treat fusion into the inferior oblique muscle. Some authors advocate
ment has been attempted with a number of medications placing all patients on artificial tears while undergoing BTX
including anticholinergics, cholinergics, dopaminergics, anti treatment. 68 Dose reductions may be considered in patients de
dopaminergics, gabaergics, and benzodiazepines. These drugs veloping problems with dry eyes due to decreased blinking. For
have not been particularly sucessfu1. 208a Surgical interventions patients who do not achieve adequate control of spasm with
include facial nerve section 38 and myectomy.141 BTX injec doses that avoid the dry eye problem, silicone punctal plugs pre
tions about the eye have been used for blepharospasm since venting tear outflow may keep the eyes wetter and allow more
1983 with an overall response rate of approximately 93% and effective doses of BTX to be used. 25 Excessive orbicularis oculi
are the recognized treatment of choice.68 weakness can result in incomplete eye closure during sleep.
The orbicularis oculi muscle is divided into 3 parts: orbital, Patients with this complication should keep the cornea moist at
preseptal, and pretarsal. Using the bony orbital rim as an night with Lacrilube and an eyepatch. BTX has been reported to
anatomic landmark, injections are made in the medial and lat cause a transient increase in intraocular pressure (lOP) of 4
eral aspects of the upper lid. Keeping the injections close to the mmHg or more in 18 of 100 patients receiving injection into or
eyelash as medial and lateral as possible and directing the bicularis oculi for essential blepharospasm. 139 The elevations
needle tip away from the center of the eye help to minimize the were demonstrated 13-15 days after treatment and resolved by
spread of toxin to the levator palpebrae superioris, and develop 28-30 days after treatment in most subjects. The increase in
ment of unwelcome ptosis. 25 Unintended penetration of the or lOP was with each injection in affected patients. In these cases,
bital septum, a thin membrane separating the eyelid proper from diffusing toxin is believed to affect autonomic cholinergic path
the orbital compartment, can result in toxin deposition posteri ways. Acetozolamide is given for 14 days to patients demon
orly and levator weakness. 68 Upper lid doses should be mini strating increased lOP after Botox injection. 139
mized in patients whose treatment is frequently complicated by
ptosis. Limiting toxin injection to the brow may be sufficient. 68 HEMIFACIAL SPASM
There is some variability in the dose and injection sites reported
Hemifacial spasm (HFS) is characterized by brief involun
tary, nonsupressible, synkinetic co-contraction of muscles in
nervated by different branches of the facial nerve. Idiopathic
cases are believed to be caused by microvascular compression
of the 7th nerve at the root entry zone resulting in a focal area
of demyelination and ephaptic nerve impulse transmission. 25
HFS due to posterior fossa mass lesions « I % of cases) re
quire neurosurgical intervention. 72 There are reports of patients
benefiting from treatment with carbamazepine. 2 Surgical de
compression for idiopathic HFS is curative 90% of the time
with low morbidity and mortality,2°S BTX therapy presents an
alternative to surgery that is simple, safe, and effective for the
majority of patients treated (Fig. 13-28). Primary HFS should
be distinguished from aberrant regeneration of the facial nerve
as a sequela of Bell's palsy that may appear clinically similar.
The injection technique and side effects of orbicularis oculi in
jection for HFS is similar to that described for blepharospasm.
In hemifacial spasm, synkinetic spasms often involve lower
FIGURE. , 3-2B. Moderate hemifacial spasm of the L face. facial muscles.
Before (left) and 2 weeks after treatment with BTX injection (right). There are a few pitfalls to avoid with treatment of lower facial
(From Bigian AW. Kim S: Management of hemifacial spasm with botu muscles. Deep injections in risorius can result in weakness of the
linum A toxin. In Jankovic J. Hallett M (eds):Therapy with Botulinum underlying buccinator muscle with biting of the inside of the
Toxin. New York, Marcel Dekker. 1994, pp 353-359, with permission.) cheek,2oaa Injections into the orbicularis oris can produce an
Chapter 13 CHEMICAL DENERVATION - 497
FIGURE 13-29. Patient before and after contralateral injection of BTX to increase facial symmetry during active expression.
A,Asymmetric exposure of teeth and depressed excursions of the nasolabial fold and lateral angle of the mouth during smiling. B,Asymmetry is
corrected by contralateral injections. (From Borodic GE: Hemifacial spasm: Evaluation and management with empahsis on botulinum toxin therapy.
In Jankovic J, Hallett M (eds): Therapy with Botulinum Toxin. New York, Marcel Dekker, 1994. pp 331-351, with permission.)
oddly shaped mouth or eversion of the lips.2°S. Injections of ele tongue movements and jaw deviation. Jaw dystonias may be
vators of the angle of the mouth such as zygomaticus major can classified as predominantly jaw opening (10), jaw closing (JC),
result in cosmetically undesirable smile asymmetry. While some or jaw deviating (JD). Physicians treating jaw dystonia with
degree of asymmetry may be present at rest, the difference is BTX must be very familiar with the local anatomy and should
generally much more apparent with active facial expression. This be prepared to manage complications of therapy. Intraoral injec
phenomenon is referred to as facial dynamic asymmetry.25 The tions should be undertaken only by a physician trained in the
patient should be reassured that the asymmetry is due to BTX in anatomy and physiology of the mouth and pharynx with equip
jection and will resolve as the effect of the medication wears off. ment to manage complications close at hand. 28
The contralateral side may be injected with BTX to produce a Pterygoid injections require EMG localization as these mus
more symmetric appearance when smiling if the degree of asym cles are deep and cannot be palpated. EMG can be used in other
metry is distressing to the patient (Fig. 13-29).25 Patients who muscles to improve accuracy and consistency and minimize
desire this intervention should be counseled that the characteris dose. Recruitment of crisp MVAPs during activation of the tar
tic appearance of their smile will change and that there may be geted muscle confirms correct placement. Toxin is diluted to 25
some impaired movement of the upper lip, likely to be most no Vlml and is distributed over 3-5 sites per muscle. Doses recom
table when speaking. Twitching in lower facial muscles will be mended for treatment of OMD are provided in Table 13-7.
adequately controlled by injections of the lower eyelids in some Serious side effects are not common and are largely related to
patients due to downward diffusion of the toxin or good control excessive local weakness. Treatment of jaw dystonia with BTX
of the eyelid "triggering" muscles. 2°S. If involvement of lower may be complicated by dysphagia, particularly with targeting of
facial muscles is mild, it is probably best to avoid lower facial in the digastric muscles. 28 Excessive weakness of jaw closure may
jections. Injection of muscles of the lower face may be needed if occur with treatment of jaw-closure dystonia. One patient has
lower facial spasms cannot be acceptably controlled with eyelid
injections. Table 13-6 provides a guideline for starting doses in TABLE 13-6. Recommened Botox Starting Doses for
several facial muscles commonly involved in HFS. Lower doses Hemifacial Spasm
may be required in patients treated for HFS secondary to Bell's
palsy as residual weakness may be present. Muscle Starting Dose
Fifty-seven patients with HFS were treated with BTX injection Orbicularis oculi 12.5-25 U in 4-5 divided doses
in an open-label study. All reported some improvement in the fre levator labii superior 5.0 U
quency and intensity of their spasms. J J The mean disability score Zygomaticus major 2.5 U
before treatment was 6.4 ± 1.2 on a rating scale for involuntary
Risorius 5.0 U
movements described by Marsden and Schachter. This scale as
signs patients a rating between 0 (lowest disability) and 8 (highest Depressor labii inferior 5.0 U
disability).137a This imprOVed to 1.5 ± 1.6 after treatment. Depressor anguli oris 5.0U
Frontalis IO.OU
OROMANDIBULAR DYSTONIA Platysma 2.SU
From Tsui JKC: Blepharospasm and hemifacial spasm. Workshop demonstrating
Oromandibular dystonia (OMD) involves lower facial mus the use of botulinum toxin. American Academy of Neurology. New Orleans. 1999.
cles of mastication and tongue musculature, producing involuntary pp 6)...66, with permission.
498 - PART II BASIC AND ADVANCED TECHNIQUES
TABLE I 3-7. Recommended Doses of Botox for by the patient. Care must be taken to distinguish dystonic
Oromandibular Dystonia muscle activity from muscle activity consciously or uncon
Muscle Median Dose ± SD Range sciously compensating for the abnormal involuntary move
ment. 168 Patients should be specifically asked to allow the
Masseter 24.5 ± 7.7 U 2.0-100.0 U affected limb to deviate without any compensatory effort so that
Temporalis 18.5 ± 11.9 U 2.0-75.0 U the dystonic movements can be observed. Having writer's
Medial pterygoid 16.3 ± 8.1 U 5.0-40.0 U cramp patients write with the unaffected hand can bring out dys
tonic movements in the hand at rest. The muscles involved in
Lateral pytergoid 15.9 ± 8.7 U 2.5-60.0 U
this activity are particularly good to target for injection. Muscle
Anterior digastric 9.8 ± 4.6 U 3.75-30.0 U targeting can be successfully based on clinical observation and
Genio/hyoglossus 18.3 ± 1.5 U 10.0-27.0 U the patient's localization of pain or tightness in most cases. 171 It
From Brin MF. Blitzer A. Herman S, Stewart C: Oromandibular dystonia: Treat is important to reassess the pattern of muscle involvement
ment of 96 patients with botulinum toxin type A. In Jankovic J. Hallett M (eds): before each injection because BTX treatment may alter the pat
Therapy with Botulinum Toxin. New York, Marcel Dekker. 1994. pp 429-425. tern of activation or unmask muscles not previously recognized
with permission. as involved. 115 EMG should be considered to define the distribu
tion of dystonic muscle activity only when injection of clini
been reported to have developed jaw closure weakness severe cally selected muscles repeatedly fails to yield the desired
enough to require use of an elastic bandage wrapped around the clinical result despite increases in dose. This procedure is tech
jaw for eating. Pterygoid injections may be complicated by rhi nically difficult, time-consuming, and usually unnecessary.
nolalia or nasal regurgitation. Adverse effects occur in 11.8% There are many pitfalls. Dystonic muscle activity cannot be dis
and 17.5% of patients in the lC and 10 groups, respectively. tinguished from voluntary muscle activity on EMG. Discomfort
Patients with mixed 10 and ID were categorized as 10. There caused by needle or wire electrodes may affect the pattern of
were 14 instances of dysphagia, but only one instance of dys muscle involvement producing misleading results. 171
phagia was severe enough to require a change in diet. Other ad The goal of BTX therapy should be clear in the mind of the
verse effects included hematoma, pain, weakness in chewing, patient and the treating physician before undertaking treatment.
nasal speech, breathy voice, and dysarthria. Thirty-seven to In a highly focal limb dystonia such as writer's cramp or a mu
45% of 96 patients improved in function with BTX injection for sician's dystonia the goal might be to improve the quality of
jaw dystonia. 28 The duration of benefit was approximately 3 writing or playing an instrument, to reduce pain, or to correct
months in patients treated for masticatory spasm. I I abnormal movements. Improved range of motion, posture, or
pain reduction may be more appropriate goals than restoration
LIMB DYSTONIA of normal function in patients with segmental or generalized
dystonia. Tremor is often a prominent feature of dystonia and
Writer's cramp is the most common focal limb dystonia. muscles involved in dystonic tremor can be treated with the
Patients typically complain of hand or forearm muscle tigtness same outcome as the underlying dystonia. 168
while writing. Abnormal involuntary postures of the fingers, EMG confirmation of needle electrode placement during in
wrist, or more proximal muscles may occur. The abnormality jections is of particular importance in the small, deep, overlap
occurs only while writing and tends to worsen with longer writ ping muscles of the arm and forearm. The anatomy of the FDS
ing efforts. The abnormality resolves with cessation of writing. muscle, a morphologically complex muscle has been de
Writing becomes slow, effortful, and may be painful over time. scribed in detail to provide guidance on the optimal injection
The patient may have difficulty holding or controlling the pen. site for each fascicle when BTX is used to treat writer's or
Other focal occupational dystonias may afflict musicians, muscician's cramp involving flexion of specific fingers. 13
golfers, and even surgeons with devastating effect. Limb dystonia Passive stretch of a muscle or muscle fasicle with the needle
may be an isolated focal problem or may be part of a segmental correctly placed will produce visible movement. This tech
or generalized dystonia. nique can be used as an alterative to EMG guidance in situa
The treatment options in limb dystonia are similar to those tions when EMG is not available. Needle position can also be
for other forms of focal dystonia. Many patients with writer's confirmed by passing a small current through the needle to
cramp will attempt to switch writing to the opposite hand as an produce muscle contraction. I 15
initial intervention. Twenty-five percent of those who do switch The most common side effect is functionally significant
hands subsequently develop dystonia in the nondominant weakness in either a targeted muscle or an adjacent muscle.
hand.138 BTX has been used to treat limb dystonia for over a Development of finger extensor weakness is commonly re
decade and has been demonstrated to be safe and effective. ported as an unintended complication of injection of the ECR.171
Evaluation focuses on selection of muscles for injection once Weakness of ulnar finger flexors can be seen with injection of
the diagnosis of dystonia is established. The patient should be FCU, and injection of one fasicle of EDC, FDS, or FDP can
examined at rest and performing tasks that bring out the dys result in weakness of adjacent fascicles. Table 13-8 provides
tonic movement such as writing or playing a musical instru some recommended doses for muscles commonly treated for
ment. Writer's cramp patients should write long enough to writer's cramp.
reproduce abnormal symptoms. Examination of other activities Eleven of 12 writer's cramp patients treated in an open-label
such as sequentially tapping the fingers on a tabletop or drawing trial with EMG-Iocalized BTX injections reported some degree
a spiral may be helpful. The affected limb should be observed of improvement. 171 Five of 15 reported weakness adversely af
for obvious distortions of posture such as finger or wrist flexion fecting function that was brief in duration (1-2 weeks). Clinical
or extension with writing. Some patients have pain or muscle benefit was sustained for 4-13 weeks, and one patient was free
tightness without any clear dystonic posturing. The limb can be of symptoms for 9 months. Twenty writer's cramp patients
palpated for muscle tightness in areas described as uncomfortable treated in a double-blind BTX investigation were assessed for
Chapter 13 CHEMICAL DENERVATION - 499
writing. 207 Evaluation included speed and accuracy of pen con TABLE 13-8. Recommended Botox Doses for
trol, completion of Gibson's maze, speed and legibility of writ Writer's Cramp
ing copying standard passage, and subjective assessment of Mean
writing. 82 All had weakness in injected muscles after receiving Starting Optimal
BTX. Speed and accuracy of pen control was significantly im Muscle Dose Dose Range
proved in the BTX-injected group. There was no corresponding
Flexor digitorum sublimis IOU 20 U 2.5-40U
improvement in the placebo group. Improvement was also sig
nificant regarding the speed of completion and reduction in Flexor digitorum profundus IOU IOU 2.5-20 U
errors on Gibson's maze for BTX-injected patients. Writing Flexor pollicis longus IOU IOU 2.5-25 U
speed improved in 7 BTX-injected patients and writing was Flexor carpi ulnaris ISU 20U 10-40 U
scored as better in 4 subjects. Patients showing improved writ
Extensor digitorum communis ISU IOU 5-20U
ing skills were those with significant wrist-joint deviation.
Writing worsened in one patient injected with BTX due to de Flexor carpi radialis 15U 25 U 10-30 U
velopment of transiently excessive local weakness. Eight of 12 Extensor carpi ulnaris ISU 20 U 10-50 U
patients reportipg pain prior to injection had relief of pain. Extensor pollicis longus 5U IOU 5-IOU
Patients receiving placebo experienced no change. There were
Extensor carpi radialis IOU 20U 10-30 U
no other side effects described. In 1996 Wissel and his col
leagues used a standardized writer's cramp rating scale (WCRS) Extensor indicis proprius 2.5 U SU 2.5-10 U
to demonstrate significant post-treatment improvement in 31 Flexor pollicis brevis 5U 5U 2.S-S U
patients treated in an open-label with Dysport injections. Thirty Extensor pollicis brevis 2.5 U 2.5 U 2.5 U
one patients demonstrated significant post-treatment improve
Adductor pollicis 2.S U 2.5 U 2.5 U
ment on the WCRS.212 The most commonly treated muscles in
this study were FCU, FCR, FDS II and III, FPL, and ECU. Pronator teres IOU 20U 10-30 U
Seventy-six percent of patients reported more than 20% subjec Supinator 15U IOU 10-15 U
tive improvement. The mean response latency was 7.6 days Interossei SU SU SU
(range 1-15 days) with a mean duration of improvement of 59.6
Lumbricals 15 U 30U 15-30 U
days (range 6-195 days). Weakness was demonstrated in 27/31
patients but only functionally relevant in 3 instances. Computer Pronator quadratus SU SU SU
based writing speed analysis was significantly improved after From Karp SI: Treatment of limb dystonia with botulinum toxin. Workshop
treatment. WCRS scores assessed through blinded videotape demonstrating the use of tobulinum toxin. American Academy of Neurology,
review by 4 independent raters showed good reliability between New Orleans. 1999. pp I 19-132. with permission.
raters and significant improvement in patients before and after
treatment. frequently does not respond to medication. Botox therapy was
In an open-label study of 18 muscians with focal dystonia af studied in an open-label trial in 78 patients with a variety of
fecting ability to play, 83% of patients had improved ability to tremors. lOS Tremor was felt to have been dystonic in 14, essential
play with at least one injection. 46 Duration of the effect was 3-4 in 12, and mixed dystonic and essential in 52 patients. Two
months. Unfortunately, for a majority of the treated patients, the thirds of the patients in this study experienced improvement in
degree of improvement was insufficient to permit the level of tremor severity of at least one point on a 0-4 scale. There was no
performance required or desired by the patient. It appears that change in tremor frequency. A single-blind, placebo-controlled
the degree of improvement obtained with BTX is generally less
than that required for a professional musician to return to his or
her premorbid level of play.168 TABLE 13-9. Recommended Doses of Botox for
Therapy for tremor must reduce the tremor and improve func Pectoralis major 30U 60U 20-200 U
tion to be considered sucessful. Functional disability resulting Pronator teres 20U 25 U 10-30U
from treatment should not exceed the benefit in reduction of
Deltoid 20U 40 U 15-60 U
tremor amplitude. The use of BTX to treat focal dystonia includ
ing that complicated by tremor has been discussed. This section Infraspinatus 30U SOU 30-60 U
primarily addresses the treatment of nondystonic limb tremor in Teres minor 30U SOU 30-60U
cluding essential and parkinsonian tremor. Essential tremor (ET)
Biceps 15U SOU 15-80U
as well as rest and action tremors associated with Parkinson's
disease (PD) generally respond well to medical management. Levator scapulae 15 U 30U 15-50 U
When medical management has proven inadequate, BTX has From Karp SI:Worshop demonstrating the use of botulinum toxin. American
been studied as a therapeutic alternative. Essential head tremor Academn)f Neurology. New Orleans, 1999, pp I 19-132. with permission.
500 - PART II BASIC AND ADVANCED TECHNIQUES
TABLE 13·10. Recommended Botox Doses for Lower (TCD), and 14 had head tremor (HT) without dystonia. Patients
Limb Dystonia in the HT group had received a variety of pharmacologic inter
Mean ventions including propranolol, primidone, trihexyPhenidyl, or
Starting Optimal tiapride without significant improvement. Clinical grading by
Muscle Dose Dose Range the Tsui scale and a 4-point pain scale was performed before
treatment and 2-3 weeks following injection along with qu&nti
Tibialis posterior SOU 200 U 40-600 U
tative tremor recordings using a bidirectional accelerometer
Extensor hallucis longus 20U 60U 30-100U placed on the forehead. 206 Muscle selection was based on visible
Tibialis anterior 100U 120U 100-140 U head deviation and palpable oscillation of cervical muscles plus
Extensor digitorum longus 15 U 55 U SO-6OU
analysis of simultaneous EMG recordings from 6 cervical mus
cles. Forty patients reported subjective improvement while three
Extensor digitorum brevis 12.SU 55 U 4O-70U TCD patients reported no improvement. Treatment significantly
Flexor digitorum longus 40U 70U 40-100 U improved both Tsui scores (10.2-5.2 in HT; 3.1-11 in TCD) and
Adductor digiti quinti 5U SOU SOU pain scale scores (1.5-0.8 in TCD; 1.0-0.4 in HT). Tremor am
plitude decreased in both groups without change in tremor fre
Gastrocnemius/soleus SOU 100U 100U
quency. Mild, transient side effects including local pain, neck
Semimembranosus 40U 40U 40U weakness, and dysphagia occurred equally in both groups (39%
Flexor brevis SOU SOU SOU TCD; 40% HT). No side effects required specific medical inter
From Karp BI:Treatment of limb dystonia with botulinum toxin. Workshop vention.213
demonstrating the use of botulinum toxin. American Academy of Neurology. BTX used in 6 PD patients and 1 ET patient produced mild to
New Orleans. 1999. pp 119-132. with permission. marked improvement with a mean change of 2.6 on a 0-4 global
rating scale in an open-label pilot study. Three showed more
than 50% improvement in tremor severity on both clinical rating
study of BTX-A subsequently involved 21 patients with dis scales and objective measurements.203 Twelve PD and 14 ET pa
abling nondystonic tremors refractory to medical manage tients were treated in a subsequent larger open-label triaJ.204 No
ment. LOI Patients were divided into two groups: patients with objective effect was seen in the PD patients as a group despite
Parkinson-like tremor and patients with ET. Half the patients ex moderate to marked improvement reported subjectively by pa
perienced> 30% benefit with placebo. Ten patients benefited by tients. Patients with distal tremors had more benefit than pa
more than 30% beyond placebo effect after treatment with BTX. tients with proximal tremors. Seven patients treated with BTX
Statistically significant improvement was demonstrated in pos in a double-blind study of parkinsonian rest tremor demon
tural tremor amplitude as measured by accelerometer, but there strated functional improvement of 24% in time to spill water
was no statistically significant improvement in rest tremor am and in maximum water spilled, and 38.6% improvement in
plitude. In this study, a standardized group of extensor and flexor maximum accelerometric displacement at one month. The
muscles was injected and a standardized initial dose of 50 U was normal saline control group experienced no effect. Benefits
divided equally between extensor and flexor muscles for the first were largely gone by 3 months. Side effects included a median
2 patients. This initial dose resulted in significant focal weakness 20% decrease in finger extensor strength that was not function
in the first 2 patients studied, and the dose was subsequently ally significant.8
halved to 25 U and distributed over a wider range of muscles. Case reports in the literature regarding the use of BTX to treat
This particular study involved a single treatment with placebo less common types of tremor include a description of successful
and with Botox for each patient. There was, therefore, no attempt treatment of hereditary trembling chin with BTX injection of
made to gradually titrate the dose upward or adjust the muscles the mentalis muscle.1l7 Vertical (yes-yes) cerebellar head tremor
selected over a series of injections to optimize the clinical result. resulting from a bilateral cerebellar infarct has been treated with
It is possible that some nonresponding patients may have im Dysport. This tremor was a 2-3 Hz rest and postural tremor
proved at higher doses of toxin. which improved markedly after injection of 80 U into the right
Ten patients with ET were studied in a placebo-controlled SCM and 120 U each into both splenius capitis muscles. Tremor
trial of Botox therapy.157 All patients had side-to-side (no-no) resolved completely 5 weeks later after injection of 80 U into
head tremors. Forty-unit doses were injected into each stern the left SCM and 80 U each into the spenius capitis muscles.16
ocleidomastoid (SCM) muscle, and 60 U doses were injected
into each splenius capitis. Placement was confirmed by EMG. SPASTICITY
Normal saline injections were used for placebo. Five of 10 pa
tients had moderate to marked improvement after a single treat Spasticity is a velocity-dependent increase in stretch reflex
ment with Botox. A single subject had mild improvement and 4 activity. Disruption of pyramidal pathways impairs or elimi
patients had no improvement. Only 1 subject had improvement nates descending inhibition of gamma motorneuron activity.
with placebo in this study. Eighty percent of subjects with mod Spastic muscle overactivity may result in contracture, abnormal
erate to marked benefit had associated objective neck weakness. posture, and pain. Both dystonia and spasticity share excessive
No subject had side effects requiring intervention. Patients with involuntary muscle contraction as the symptomatic conse
non dystonic head tremor treated in an open-label trial with quence of disordered central nervous system physiology.
BTX-A demonstrated statistically significant improvement in Imbalance in muscle tone between agonist and antagonist mus
the Webster tremor scale and in the Global Disability Scale.206 cles produces postures characteristic for spasticity. BTX can be
Targeted muscles were determined by clinical examination and used to selectively weaken muscles to improve the balance in
by tremor analysis. EMG guidance was used for toxin place muscle tone across one or more joints, but does not correct the
ment. Head tremor was quantitatively assessed in 43 patients underlying etiologic physiology and cannot directly improve
treated with Dysport. Twenty-nine had tremulous cervical dystonia function or performance.
Chapter 13 CHEMICAL DENERVATION - 501
The traditional annamentarium for phannacologic spasticity side effects. Four phannacologic agents (diazepam, dantrolene,
treatment has included systemic, regional, and localized modal baclofen, and tizanidine) are approved by the FDA for treatment
ities. Peripheral aggravators of muscle overactivity such as pres of spasticity as a symptom of a CNS disorder in adults. 89
sure sores, ingrown toenails, urinary tract infections, or BTX can be used to selectively weaken muscles to improve the
excessively restrictive clothing should be sought out and elimi balance in muscle tone across one or more joints, but does not cor
nated before considering phannacologic intervention. 88 This ag rect the underlying physiology and cannot directly improve func
gravation of muscle activity may result from stimulation of tion or performance. Targeted BTX injections may reduce
afferents such as flexor-reflex afferents. 133 Physical therapy may excessive muscle tone and associated pain, improve postural abnor
be helpful in the early management of spasticity or in chronic malities reducing the need for splinting and bracing, prevent con
patients as part of a combined approach in which physical meth tractures, reduce nursing care, and improve hygiene maintenance.
ods are used to optimize the benefits of other therapies. 190. BTX can be used together with other treatment modalities, includ
Systemic phannacologic treatments would be indicated in the ing systemic medication, intrathecal baclofen pump, or surgery.
setting of diffuse excessive muscle activity, as in anoxic, toxic, Effects and side effects are reversible so the injected muscles and
metabolic, inflammatory, degenerative, and some vascular or the dose can be adjusted over time to produce maximum benefit
traumatic conditions. Clinical conditions commonly resulting in and minimize iatrogenic functional deficits. BTX injections have
diffuse spasticity include multiple sclerosis, spinal cord injury, been studied in several neurologic disorders characterized by spas
stroke, traumatic brain injury, and cerebral palsy. Numerous ticity including multiple sclerosis, traumatic brain injury, cerebral
medications have demonstrated efficacy in reduction of muscle palsy, spinal cord injury and stroke. IO•191 Recommended doses are
stretch reflexes, but none has been established as universally ef listed in Tables 13-11 and 13-12 and Figures 13-30 and 13-31.
ficacious in reducing excessive muscle activity caused by le Placebo or 400 U of BTX were injected into thigh adductor
sions of central motor pathways, and all have potentially serious muscles (100 U in adductor brevis; 100 U in adductor longus:
502 - PART II BASIC AND ADVANCED TECHNIQUES
From Brin MF: Cervical dystonia--syllabus for treatment of dystonia:Workshop demonstrating the use of botulinum toxin. American Academy of Neurology, New
200 U in adductor magnus) in 10 nonambulatory multiple scle In an open-label injection of 100-400 of BTX into thigh ad
rosis patients with thigh adductor contractions severe enough to ductors, hamstrings, gastrocnemius-soleus, and posterior tibial
interfere with activities of daily living (ADLs) and hygiene. 191 muscle groups, 10 of 11 myelopathic patients demonstrated sig
Patients received injection with the alternative therapy at 3 nificant improvement on one or more scales during a 2 month
months in this double-blind, placebo-controlled, randomized assessment period. Patients were evaluated for tone, joint mo
study. Patients receiving BTX had a reduction in spasticity score bility, gait, and global function. 20 Seven of 12 spastic parapare
from a mean of7.9 to 4.7 at 6 weeks post-injection. The same pa sis patients receiving open-label BTX injection of thigh
tients injected with placebo had an increase in spasticity score adductors reported decreased spasticity. Eight of lOin this same
from a mean of 6.8 to 7.8 at 6 weeks. Hygiene scores also demon study reported decreased speed in ambulation.
strated a significant benefit with BTX over placebo. No adverse An open-label study evaluated BTX injection in 15 children
effects were reported. Small open-label studies also suggested with cerebral palsy (5 hemiplegic, 5 diplegic, 5 quadriplegic).5
that BTX was effective in reducing lower limb spasticily.1O·21 Patients had spasticity, dystonia, or both. Overactive muscles
Chapter 13 CHEMICAL DENERVATION - SOl
risk of excessive weakness as the muscles injected are often al Ethyl alcohol in dilutions of 35-60% has been used to achieve
ready paretic and nonfunctional. temporary nerve block in patients with spasticity. Like phenol,
alcohol denatures the protein in nerve tissue. Treatment experi
Chemical Neurolysis for Treatment of Spasticity ence with alcohol for spasticity has predominantly involved in
Chemical neurolysis with phenol and alcohol injections has tramuscular injection for the treatment of cerebral palsy in
also been used to treat spasticity. These agents can be adminis children. 88 Forty-five percent alcohol injected into the mptor
tered locally to treat spasticity, avoiding systemic side effects. point of muscles was demonstrated to reduced spasticity without
Phenol (carboxylic acid) has been widely used as an injectable affecting voluntary strength in children with cerebral palsy in the
agent in the regional treatment of spasticity.215 Phenol can be in mid-1960s. 201 Results lasted for 6-12 months with some patients
jected at the muscle's motor point or directly into nerve where it deriving benefit for as long as 2-3 years. Forty-five percent dilu
denatures the protein in nerve fibers. Phenol, in low concentra tion of alcohol injected in large quantities (10-40 ml) into multi
tion, has the properties of a local anesthetic. Protein coagulation ple sites in targeted muscles were also reported to improve
and necrosis are seen with concentrations greater than 5%.215 spasticity with preserved strength and sensation. 156 Other investi
Phenol causes protein coagulation and necrosis at concentra gators have reported shorter duration of benefit of 1-6 weeks. 40
tions greater than 5%.1l7 Alcohol can be used similarly to dehy Shortcomings of dilutions at 35-45% include pain with injec
drate nerve tissue resulting in sclerosis of the nerve fibers and tion, transient symptoms of systemic toxicity, and skin irritation
destruction of the myelin sheath. Disadvantages of phenol or al or ulceration. 40,121 Conscious sedation or general anesthesia may
cohol injections include pain and dysesthesias that may last be of benefit for the injection procedure. 121
weeks to months, variable duration of effect, and potential car Local anesthetics with a short duration of action have been
diac arrythmias. In some cases, effects can be permanent. 190a used prior to chemical neurolysis to diagnostically determine
Phenol or alcohol injections may have particular benefit in large the mechanism of impairment (increased tone versus contrac
proximal muscles that would require BTX doses exceeding rec ture) and to predict expected benefit of a longer-lasting block. 8g
ommended total doses to achieve benefit. Randomized, placebo-controlled studies are needed to confirm
Phenol has been used intrathecally, epidurally, intraneurally, the safety and efficacy of chemical neurolysis for spasticity.
perineurally, and intramuscularly for treatment of pain and spas
ticity.215 Intrathecal and epidural injections introduced in the Surgery for Spasticity
1950s are no longer in common use. Perineural, intraneural, and Surgical treatments of spasticity have been aimed at four sites
intramuscular injections are used in the treatment of spasticity of potential intervention: the brain, the spinal cord, peripheral
alone or in some cases in combination with BTX. Phenol injec nerve, and muscle. Stereotactic surgery has been performed for
tion provides temporary reduction in spasticity producing joint symptomatic treatment of dyskinesia, rigidity, and spasticity.
contracture or interfering with function and rehabilitation. Targeting is controversial as the anatomic source for spasticity is
Temporary interruption of nerve function can prevent or correct unclear. Targets have included the globus pallidus, ventrolateral
deformities due to excessive muscle tone in patients with recently thalamic nuclei, and cerebellum. Complications of central surgi
acquired spasticity in whom the ultimate neurologic outcome is cal approaches may include sensory loss, paresthesias, weakness,
uncertain and definitive orthopedic surgery is inappropriate. 8o and recurrent spasticity.I 9Oa Twenty-eight patients treated surgi
Peripheral nerve blocks provide more complete block than motor cally for cerebral palsy were followed for a mean of 21 years
point injections. 80·117 Phenol nerve injections may be performed postoperatively. Results were good in patients with moderate to
percutaneously or using open surgical procedures with direct vi severe dyskinetic cerebral palsy but poor in patients with quadri
sualization of the nerve. Open procedures are preferred to percu plegia or diplegia with spasticity. The diffuse nature of the under
taneous injection for nerves containing both sensory and motor lying brain lesions seen in patients with spasticity suggest a
function so that the motor branches can be identified and isolated limited potential for success. Generally poor clinical results bear
to prevent post-block dysesthesia and sensory loss.149 Motor this out and provide evidence that stereotactic surgery is not war
branches are identified using a nerve stimulator. Three percent ranted in the current treatment of spasticity. Selective posterior
phenol in glycerine is injected into the exposed nerve until it be rhizotomy can accelerate progression of hip subluxation causing
comes translucent and no motor response is elicited with electri instability of the hip and the lumbar spine in cerebral palsy pa
cal nerve stimulation. 80 Neutralization with alcohol limits damage tients with underlying hip dyplasia, a common comorbidity.93
to surrounding tissue when phenol is applied directly to the
nerve. 121 The affected limb may be treated with serial casting to Patient Selection in Spasticity
correct any residual fixed contractures. 80 Open treatment of the Any limitation of range of motion to be treated with BTX
musculocutaneous and tibial nerves are described in the orthope should be passively reduceable to some extent as BTX cannot
dic literature for the treatment of elbow flexion contracture and free a frozen joint or reduce contracture. Clear goals of treat
equinovarus ankle posturing, respectively.80·lso Obturator blocks ment should be delineated and might include improved func
decrease lower limb scissoring and facilitate hip abduction. tion, posture, range of motion, hygiene, and reduced pain.
Median nerve blocks relax wrist and finger flexors. Paravertebral Patients considered for BTX therapy should have been tried on
lumbar spinal nerve blocks reduce hip flexor spasticity.1l7 medical therapies and demonstrate no benefit or unacceptable
Complications include sensory loss, dyesthesias (3-10% for sen side effects. Muscles to be injected should not be excessively
sorimotor blocks), excessive weakness, and venous thrombo wasted. Prior surgical intervention should not distort the
sis. 100.134.215 A review of the use of phenol as a neurolytic agent anatomy of the area considered for injection. BTX treatment
published in 1978 concluded the following regarding peripheral can benefit carefully selected spastic adults and children.
nerve injections for spasticity: "Apparently anyone who under Concurrent physical therapy can optimize the benefit of BTX
takes to do this should consider it only as an adjunct to other treatment. Studies comparing phenol, alcohol, and BTX to one
forms of treatment. The effect will be temporary around two another to determine if subsets of patients benefit from one
months to a year, with the shorter period more likely."215 modality over another have yet to be performed.
Chapter 13 CHEMICAL DENERVATION - 50S
/
" , '" --
! . . ,,
.....
\
\~'
\
\.:
\:
/,,/
I
I
.
...
.
I
I ,
I
.- -'.
of patients reporting improvement in pain-related depression became more pronounced and persistent. Four years after symp
was significantly greater for the BTX-only group compared to tom onset he underwent excision of a right talocalcaneonavicu
the surgery-only group (80% and 64%, respectively). Results lar osteophyte with interposition of the extensor digitorum
for the surgery-BTX group were intermediate (72%). brevis muscle. Six years after symptom onset, the patient was
Improvement in pain was similar for all groups (85% for the referred for a neurology consultation. The patient was noted to
BTX group, 88% for the surgery group, and 78% for the group have subtle posturing of the right hand with stressed gait, .and
receiving both). Unfortunately no clinical or electrophysiologic decreased arm swing on the right in addition to focal dystonia
data are presented for the involved patients, treatment was not of the right foot. On note, at age 16 the patient had a history of
randomized, and the magnitude of the effect was not reported. head trauma with loss of consciousness lasting almost a month.
This study cannot be evaluated for the presence or absence of Evaluation included normal lower limb nerve conduction
confounding variables and selection bias. The clinical condition studies and needle EMG. MRI was remarkable for a small slit
of the patients prior to treatement and the magnitude of the clin like lesion in the left basal ganglia with hemosiderin products
ical benefit is not reported. This study contains insufficient in suggesting distant history of hemorrhage. An angiogram was
formation to draw any conclusion about the efficacy of BTX for normaL
pain in purported thoracic outlet syndrome. The patient was felt to have a traumatic right hemidystonia
Some patients receiving BTX injection for the treatment of most marked in the lower limb. Pharmacologic treatment was
facial wrinkles coincidentally reported improvement in tension initiated with Artane increased to a maximum dose of 32
type headaches. 42 BTX was used to paralyze temporal muscles in mg/day in 3 divided doses for the past several years. There was
6 patients with chronic tension headache (TH) to explore the role improvement in the focal dystonia, but the patient developed
of pericranial muscle tension in TH.219 Injection was unilateral, drowsiness. fatigue, and lightheadness limiting upward titration.
leaving the contralateral side as a control. There was no signifi The medical history is remarkable for Graves' disease for
cant reduction in pain intensity or pain threshold and investiga which the patient takes synthyroid replacement medication.
tors concluded that in these muscles muscle tension played only Physical Examination. The patient is alert, oriented and co
a minor role in headache pathogenesis. It was recommended that operative with the examination. Cranial nerve examination is
other neck and posterior head muscles be similarly studied. A remarkable for decreased mimetic movement of the right side of
28-year-old woman with a 5-year history of refractory cervico the face. Motor examination is remarkable for 515 strength
genic headaches following a whiplash injury was reported to proximally and distally, slight right proximal upper limb fix and
have responded dramatically to a single BTX injection into the pronator drift. Muscle tone and mass are normal. There is nearly
symptomatic trapezius muscle in 1997. 104 Injections were re constant dystonic eversion and dorsiflexion of the right foot and
quired every 3 months to maintain the benefit. In 1998 BTX was dorsiflexion of the toes that becomes more marked with walk
revisited for refractory TH.211 In some patients TH seemed to ing. Sensation to temperature and light touch is slightly de
trigger secondary headaches falling in the migraine continuum. creased over the right face and arm. Deep tendon reflexes are
Four patients with predominantly TH who had failed extensive mildly increased in the right compared to the left arm without
efforts at conventional therapy were injected in symptomatic spread or clonus. Ankle reflexes are absent bilaterally. Plantar
areas. There was a reduction in associated myalgia and a reduc responses are bilaterally flexor. Gait is remarkable for decreased
tion in the frequency and severity of migraine-type headches. arm swing on the right and dystonic posturing of the right foot.
Eight patients with TH unresponsive to amytriptyline and physi Balance and coordination are normal.
cal therapy were injected with 25 U of Dysport in frontal, tempo Nerve Conduction Studies
ral, occipital, and SCM muscles (total dose 100 U).182 Each DSL SAmp DML MAmp NCV
patient maintained a headache diary used to calculate the area (ms) (IlV) (ms) (mV) (mls)
under the headache curve (AUC) 4 weeks before and following Nerve
treatment. The AUC was significantly reduced from 404 to 196 L peroneal 3.9 2.1 46.7
following treatment. No major side effects were reported. R peroneal Surgically absent
Headache is one of the most common complaints for which pa R Sural 3.7 10
tients seek medical attention. BTX injection will never be first R H reflex latency 30.4 ms
line therapy, as conventional medical therapy will often be L H reflex latency 30.3 ms
effective, well-tolerated, and inexpensive. If the benefit sug Needle Electromygraphy. Right lower limb muscles were
gested by these small open pilot studies is confirmed in larger studied with a monopolar needle.
placebo-controlled, randomized studies there will doubltless be a Muscle Rest activity Recruitment
subset of refractory patients using large quantities of expensive Vastus medialis Normal Normal
medications or requiring sufficient emergency department, Tibialis anterior Normal Normal
clinic, and inpatient services to make efficacious use of BTX Extensor hallucis longus Normal Normal
cost-effective. The application to the treatment of headache has Extensor digitorum brevis Normal Normal
potential to greatly expand the clinical use of BTX. Medial gastrocnemius Normal Normal
L3-L5 paraspinus Normal Normal
Illustrative Case: Distal Lower !-fmb Dystonia Impression. Normal electrodiagnostic examination aside
Reason for Referral. Foot and ankle dystonia. from the anticipated absent right peroneal motor response sec
History. A 36-year-old patient first noted the onset of right ondary to the previous surgery. Subtle post-traumatic sympto
foot pain and involuntary eversion of the right foot and toe ex matic hemiparesis with right lower limn dystonia based on
tension with walking beginning at age 22. Pain was also noted history and physical examination.
in the lateral aspect of the right lower limb. The patient was Recommendations. Botulinum toxin injections of the right
treated with a heel lift and physical therapy for a number of lower limb were recommmended to permit reduction or discon
years without symptom resolution. Over time. the symptoms tinuation of pharmacologic therapy at age 29.
Chapter 13 CHEMICAL DENERVATION - 509
Treatment Course. The patient was started with an injection 4. Aoki R. Merlino G, Spanyannis A. Wheeler L: Botox (botulinum toxin type A)
purified neurotoxin complex prepared from the new bulk toxin retains the same
of 50 U of Botox in the right peroneus tertius muscle with EMG preclinical efficacy as the original but with reduced immunogenicity. Neurology
guidance. This resulted in decreased pain and reduced require 1999;52(Suppl 2):A519-A520.
ment for Artane. After 3 injection cycles, the peroneus tertius 5. Arens U, Leary PM, Goldschmidt RB: Experience with botulinum toxin in the
(PT) dose was reduced to 40 U and 25 U doses were initiated in treatment of cerebral palsy. SAMJ 1997;87:1001-1003.
6. Aronson AE, DeSanto LW: Adductor spasmodic dysphonia three years after re
peroneus longus (PL) and extensor digitorum longus (EDL). current laryngeal nerve section. Laryngoscope 1983;93:1-8.
This produced much better control of the dystonia initially with 7. Ashton AC, Dolly JO: Microtuble dissociating drugs and A23187 reveal differ
out clinically significant weakness and permitted the patient to ences in the inhibition of synaptosomal transmitter release by botulinum toxins
types A and B. J Neurochem 1991;56:827-835.
discontinue Artane altogether at peak benefit. Because of patient 8. Bain PG. Gregory R., Hyman N: Treatment of Parkinsonian tremor with botu
discomfort with the injections, Botox injection to the PL muscle linum toxin: Results of a pilot study. Presented to the Dystonia Forum in
was temporarily delayed. However, injections without this London. 1994. Cited in Findley U: Tremor. In Moore P (ed): Handbook of
muscle proved less effective. The PL injection was reinstated. Botulinum Toxin Treatment. Oxford. Blackwell Science. 1995, pp 248-262.
9. Bakry N, Kamata Y, Simpson LL: Lectins from Triticum vulgaris and Limax
The combination of 25 U doses in EDL and PL after several in flavus are universal antagonists of botulinum neurotoxin and tetanus toxin. J
jection cycles resulted in footdrop persisting between injections. Pharmacol Exp Ther 1991;258:830-836.
EDL and PL doses were lowered. The patient has been managed 10. Benecke R: Botulinum toxin for spasm and spasticity in the lower limbs. In
Jankovic J, Hallett M (eds): Therapy with Botulinum Toxin. New York. Marcel
consistently and effectively with injections every 3 months of 40 Dekker, 1994. pp 557-565.
U in PT, 20 U in EDL, and 15 U in PL with modest weakness in II. Berardelli A. Mercouri B, Priori A: Botulinum toxin for facial-oral-mandibular
toe extension that is not functionally significant. Injections are spasms and bruxism. In Jankovic J, Hallett M (eds): Therapy with Botulinum
repeated every 3 months. The patient usually notices some return Toxin. New York. Marcel Dekker, 1994, pp 361-367.
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PART
III
PATIENT
CARE-RELATED ISSUES
Chapter 14
The Electrodiagnostic
Medicine Consultation:
Approach and Report
Generation
Daniel Dumitru, M.D., Ph.D.
Patients who present for an electrodiagnostic medicine con electrodiagnostic medicine consultation is like any other con
sultation often arrive with a consultation form requesting an sultation performed by a physician and contains essentially the
evaluation for a specific problem. This problem may be stated same subcomponents: pertinent history, directed physical exam
explicitly (e.g., possible right carpal tunnel syndrome) or gener ination, specialized examination (for our purposes, nerve con
ally (e.g., right upper limb pain). In either case, the practitioner duction studies and needle electromyographic investigation),
performing the electrodiagnostic medicine consultation is re summary of findings, impression, and, if appropriate, a plan and
sponsible for defining the appropriate electrical tests based on a recommendations for follow-up. The approach described in this
well-directed history and physical examination. The referring chapter is based on the views of the first author, who practices
physician's request is important and should be used as a guide in the United States, and is not necessarily valid for other coun
for directing the consultation, but the beginning point for any tries. In the final analysis, the primary issues of referral depend
medical consultation is the patient's chief complaint. The his on the explicit or implicit rules and agreements between refer
tory and physical examination provide the practitioner with the ring and consulting physician.
necessary information to plan a comprehensive, yet focused
electrodiagnostic examination.
Once the electrodiagnostic medicine consultation is com REPORT GENERATION
pleted and all of the data are analyzed, it is necessary to com
municate the findings. Conveying this information in a concise HISTORY
and understandable format is one of the most important aspects
of the entire electrodiagnostic evaluation. The final report can As in any other medical consultation, the history is perhaps
take many acceptable forms; there is no single "correct" way in the most important portion of the electrodiagnostic consultation
which the practitioner must document the examination and its because it forms the basis for the directed physical examination
findings. The consultation advocated in this chapter assumes and all electrical investigations. The physician's extensive train
that the electrodiagnostic examination comprises only one ing in the history and pathophysiology of disease is crucial in
aspect of a complete medical consultation. In other words, the performing a complete history directed toward the patient's
SI5
516 - PART III PATIENT CARE-RELATED ISSUES
chief presenting complaint. Certainly, most patients arrive with three major categories of diagnostic techniques: (I) central/pe
a consultation that affords the practitioner some insight into ripheral neural conduction, (2) neuromuscular junction trans
what the referring physician suspects, but it is by no means an mission, and (3) needle electromyographic analysis of skeletal
acceptable replacement for the performance of a thorough his muscle. Central/peripheral neural conduction considers the
tory and physical examination. In eliciting the patient's history, following: sensory and motor nerve conduction latencies and
the practitioner should explore the chief complaint in as much velocities; waveform morphologic considerations, such as am
detail as required to ensure an adequate accumulation of infor plitude, area, and temporal dispersion; somatosensory evoked
mation directly related to the presenting symptoms. Addi potentials; refractory period analysis; and other specialized
tionally, all related information that may be tangentially relevant techniques specifically looking at central/peripheral neural con
bears consideration. Of particular importance is a thorough un duction (e.g., F-waves and H-reflexes). The investigation of
derstanding of the nervous and musculoskeletal systems and neuromuscular transmission usually involves the evaluation of
their myriad overlapping presentations. an evoked compound muscle action potential to repetitive stim
A fundamental understanding of the pathophysiology of ulation in combination with exercise. The results of this portion
neural injury and regeneration pertains directly to the patient's of the consultation can be included as a subsection of the neural
potential complaint and eventual recovery. Detailed knowledge conduction portion of the final report. It also may be necessary
of the histologic and neurophysiologic response of the periph to evaluate neuromuscular transmission by performing single
eral neuromuscular system to injury directs the types of ques fiber electromyography. In this instance, the results may be
tions asked. The gathering of historical data must be pursued grouped with the repetitive stimulation data or included with the
until the practitioner has a clear understanding of where the needle electromyographic information. Needle electromyo
physical examination should begin to confirm or exclude each graphic analysis includes insertional activity, rest activity, and
of the differential diagnoses under consideration. motor unit morphology evaluation of amplitude, duration,
shape, and recruitment.
PHYSICAL EXAMINATION Before subjecting the patient to the above procedures, it is ab
solutely necessary to explain the procedures to the patient. This
The physical examination and history allow the practitioner is perhaps the most important aspect of the entire electrodiag
to formulate a preliminary approach to the electrodiagnostic as nostic medicine consultation; its value cannot be underestimated.
sessment of the patient's neuromuscular system. Predicated on a Frequently, well-intentioned but misinformed acquaintances of
complete, yet focused history, the physical examination is di the patient may convey an entirely unrealistic picture of the elec
rected to functional aspects of the neuromusculoskeletal system trodiagnostic medicine consultation, thus instilling a significant
related to the chief complaint. The physician who is expert in amount of misinformation and unsubstantiated fear or anxiety. It
the practice of electrodiagnostic medicine must have a com is incumbent on the practitioner to educate the patient about the
mand of the anatomy and physiology of the peripheral and cen various procedures comprising the examination and its benign,
tral nervous systems beyond that of other medical practitioners. though occasionally uncomfortable, nature. A completely in
In addition, musculoskeletal injuries associated with or mimick formed and thus more relaxed patient can cooperate more fully
ing peripheral nerve injury must be mastered. with the examination and help the practitioner collect the re
Additionally, the practitioner must be prepared to examine quired data to formulate an appropriate diagnosis and prognosis.
the cutaneous distribution of every nerve supplying all aspects The practitioner also must be cognizant of the limited technical
of the human body. It is also necessary to be able to trace each understanding of most patients and should explain carefully the
and every nerve back to the spinal cord through the various sites various portions of the consultation in simple language without
of potential entrapment as well as through the plexus and root technical jargon. Both the practitioner and patient must recog
levels from which they originate. The origins, insertions, and nize and respect the patient's right to terminate the examination
methods of activation for the skeletal muscles supplying the at anytime.
limbs, thorax, and face are also basic aspects that must be mas
tered to examine physiologic status in terms of strength, range Neural Conduction
of motion, and possible patterns of substitution. In addition to A tabular format designed by the practitioner usually is the
pursuing possible peripheral causes, it is also important to keep best way to document and convey data collected during the per
in mind central lesions that may manifest with a similar clinical formance of neural stimulation. A list of the nerves studied and
presentation. In general, an appropriate physical examination is their important parameters (latency, segmental amplitudes and
regionally directed and includes inspection, palpation, range of conduction velocities, morphology, or other relevant character
motion, and neurologic testing of sensation, strength, reflexes, istics) should be clearly noted. Motor waveform magnitude is
and appropriate provocative maneuvers. A cursory examination an important way to evaluate conduction block; therefore, am
and lack of fundamental knowledge, including an understand plitude should be recorded for all stimulation sites as well as the
ing of the histopathophysiology of neuromuscular diseases, pre technique used to measure amplitude (e.g., base-to-peak vs.
cludes one from even attempting an electrodiagnostic medicine peak-to-peak). Base-to-peak amplitude assessments are recom
consultation. mended for all motor waveforms. If abbreviations are used, they
should be designated in a legend somewhere in the final report
ELECTRICAL ASSESSMENT OFTHE because the report may be reviewed by physicians who are not
NEUROMUSCULAR SYSTEM familiar with the terminology. The author discourages the use of
accompanying reference data. It is often impractical to include
Evaluating the dynamic neurophysiologic functional status of reference data only for studies performed. As a result, a rather
the peripheral nerve, neuromuscular junction, and skeletal large table of normal values may have numerous empty spaces
muscle is the diagnostic portion of the electrodiagnostic medi for nerves not examined. It unnecessarily distracts from the im
cine consultation. For discussion purposes, we may consider portant data and invites unproductive discussion about what is
Chapter 14 THE ElECTRODIAGNOSTIC MEDICINE CONSULTATION - 517
"nonnar' for individual nerves. The practitioner should develop program can provide quantitative results describing the sig
a reference database or meticulously reproduce another labora nal. The most common way is to analyze the motor units visu
tory's recording conditions before using its reference values to ally in a qualitative manner. The experienced practitioner is
decide "nonnality." Also, all studies are interpreted in conjunc usually capable ofjudging clear abnonnalities in the signal. The
tion with the history and physical examination. human brain is good at pattern recognition, and the combined
Some portion of the data table should be reserved for the tem visual and auditory information helps the practitioner to detect
perature of the limb or specific body part. The importance of possible abnonnalities. It is better to record variables concern
temperature and its various effects on neural conduction and ing the motor units (e.g., range of durations, amplitudes) in
wavefonn morphology cannot be overemphasized. A blank some quantitative way. It is inappropriate to ask the patient to
region on the report calls attention to the necessity of recording provide a moderate to strong contraction, observe an interfer
temperature, which otherwise will be conspicuous by its ab ence pattern, and report only polyphasic potentials or durations.
sence. One also may consider a similar practice for recording Overlap of multiple motor units can give the false impression of
body height, which is an important variable for interpreting con increased polyphasic potentials and "abnormal" durations and
duction velocity results. amplitudes. The presence of satellite potentials cannot be evalu
When repetitive stimulation studies are deemed appropriate, ated without the use of a trigger and delay line.
it is important to include all of the data recorded. A convenient The second manner of measuring the signal is quantitative: a
table containing both pre-exercise and post-exercise increment trigger is used to measure the duration, amplitude, and polypha
and decrement data should be documented. The percent ampli sia of at least 20 motor units. 3 Computer evaluation can be done
tude decrement between the first and fourth or fifth response is by an analysis of the interference pattern (e.g., turns, amplitude
typically described. This same infonnation is noted for each analysis) or a template method of extracting motor units.
nerve and the side of the body examined. Single-fiber jitter and Studies of the different yields of these techniques in different
fiber density data can be easily incorporated into this segment neuromuscular disorders have not provided a clear answer as to
of the consultation. the best method. In some studies, simple qualitative visual in
spection was shown to be superior to "automated decomposi
Needle Electromyography tion electromyography"15 or interference pattern (IP) analysis. 1O,28
Perhaps the most convenient way to document the needle Several studies found a comparable yield of abnonnalities with
electromyographic findings is first to list the muscles actually IP analysis and qualitative motor unit analysis. 8•9,26 At present
examined. Standard tables containing long lists of muscles are no technique has been proved superior to the others. Even quan
cumbersome and lead to confusion and waste of time. Listing a titative motor unit analysis and qualitative visual inspection
routine set of muscles is also inappropriate because it causes the were not shown to be statistically different in detecting myopa
practitioner to use the same muscles without thinking about the thy or neuropathy.20 The best manner to evaluate the EMG
most judicious use of time for a given problem. If a particular signal is still a matter of debate, and more studies are needed.
disease requires the examination of muscles other than those Globally, a sensitivity of 60-90% and a specificity of about 80%
commonly assessed, the practitioner may not think of the most are reported for the different techniques. 8•9,1O.2o In short, needle
appropriate muscle or be required to alter the set fonnat and electromyography is still an art and the best way to perfonn the
create an untidy fonn. study depends on the practitioner's experience and training and
Several columns designating the activity investigated should the capabilities of the EMG instrument. In the authors' opinion,
be included next to the list of examined muscles. Some of these a clear and consistent way of recording and reporting data (as
areas include insertional activity, rest activity (e.g., positive quantitative as possible) is important for other physicians to ap
sharp waves, fibrillation potentials, fasciculations), motor unit preciate what has been done and is necessary for follow-up
recruitment, motor unit activation (interference pattern), and, studies. It is also a good idea to state what type of needle elec
for quantitative needle electromyography, motor unit action po trode is used because it has obvious implications for motor unit
tential parameters (e.g., phases, amplitude, duration, rise time). action potential parameters, particularly amplitude and number
Atypical potentials (e.g., fasciculation potentials, complex of phases.
repetitive discharges, myokymic potentials) do not require
quantitative analysis and can simply be noted in an accompany Summary of Findings
ing paragraph describing the abnonnality at the bottom of the After collection of a significant amount of data, it is usually
columnar data. A number of important comments are appropri good practice to summarize the pertinent aspects of the infor
ate at this point. A clear distinction should be made between re mation. Portions of the examination that directly relate to the
cruitment and activation (interference pattern) analysis. patient's symptoms and findings suggestive of additional dis
Recruitment may be nonnal, increased (multiple motor units ease should be noted. This aspect of the consultation provides
firing at relatively rapid rates at low force production), or re substantiation for the rationale underlying electrical studies or
duced (decreased numbers of motor units firing at very rapid investigated muscles that may not directly correspond to the
rates with minimal to moderate force of contraction). Re original reason for the consultation request. In other words,
cruitment, which refers to the specific sequential activation of unlike an electrocardiogram, which is perfonned in a standard
motor units with increasing force production, may be quantified manner each time, the electrodiagnostic medicine consultation
by noting the recruitment interval, recruitment frequency, or re is a dynamic process that evolves with the collection and imme
cruitment ratio. Asking the patient to contract a muscle maxi diate interpretation of data.
mally and observing an interference pattern has questionable As each portion of the consultation emerges, a number of
diagnostic yield because of adverse effects of patient coopera potential disease states not in the original differential diagno
tion, pain, and other subjective factors. sis may be considered. Practitioners must be prepared to alter
The EMG signal can be interpreted by the physician in two the anticipated series of nerves or muscles examined and rely
ways (qualitative or quantitative). Alternatively, a computer on their background and understanding of the pathophysiology
518 - PART III PATIENT CARE-RELATED ISSUES
and diagnosis of disease to fonnulate the most appropriate in Additionally, a number of other disorders may emerge as a
vestigation design. This is an important reason for not per result of the electrical testing. For example, a patient may com
forming each consultation in the same manner. Dynamic plain of numbness and tingling in the first two digits of the right
interplay between the physician's diagnostic skills and the hand. After a complete electrodiagnostic medicine examination,
electrical results is required to arrive at a correct and unbi the possibilities of carpal tunnel syndrome, cervical radiculopa
ased diagnosis that best explains all of the patient's symp thy, and other entrapment neuropathies are completely ruleq out
toms. Summarizing the data often allows the opportunity to with respect to their electrical manifestations. On examining the
consider the infonnation as a whole and how it interrelates to patient, however, overt trigger points reproducing the patient's
the patient's presentation. At times, additional investigations symptoms may be found. In this instance, the appropriate elec
may be inspired by the act of summarizing results. Once the trodiagnostic medicine impression is the recognition of a
electrical studies have been structured in an organized way, nonnal study. The clinical impression based solely on the his
the process of formulating an impression is made consider tory and physical examination is a trigger-point problem. It is
ably easier. appropriate to infonn the referring physician of the possibility
of a musculoskeletal component to the patient's symptoms.
Medical Impression Some practitioners may wish to include this observation in the
The fonnulation of a medical impression involves organizing overall impression, but the first author prefers to distinguish
all of the clinical and electrical information into a single or a clearly between the two diagnoses based on electrical findings
number of diagnoses that may account for the patient's symp and findings reached by history and physical examination alone.
toms. Depending on the findings of the history, physical exami
nation, and electrical studies, the physician may wish to consider Recommendations
documenting two subcomponents in the final impression: elec The final portion of the electrodiagnostic medicine consulta
trodiagnostic medicine impression and clinical impression. tion is the recommendations section. On request or if appropri
Electrodiagnostic Medicine Impression. In a strict sense, ate, the practitioner makes a number of relevant suggestions for
the electrodiagnostic medicine impression refers primarily to patient management, based on the electrophysiologic findings.
potential diagnoses, based on the electrical infonnation ob The referring physician will value an expert opinion about vari
tained either through neural conduction or intramuscular needle ous treatment options that may benefit the patient.
placement in conjunction with the history and physical exami Because both diagnosis and prognosis often can be offered, it
nation. The impression should be worded clearly and concisely is reasonable to include a number of treatment options to which
to impart as much infonnation as possible and avoid confusion. the patient may respond best. If additional confirmatory testing
Occasionally it may be necessary to provide an explanatory nar would be beneficial, particularly in a confounding instance, the
rative if a definitive diagnosis is in doubt. This situation may most efficacious test can be recommended based on the physio
occur with mixed findings or only a few subtle abnonnalities in logic status of the nervous system and presumptive lesion loca
a scattered distribution. The practitioner must be vigilant to tion. For example, biopsy of a particular muscle may be
anomalous innervation patterns or several diseases that may suggested by electrophysiologic findings. The necessity of a
manifest in similar presentations. A good practice is to offer a return neurophysiologic evaluation and a suggested time frame
number of specific etiologies, if appropriate. also should be noted at the end of the recommendations section.
Keep in mind that the nervous system, despite its complex The first author prefers direct verbal communication with the
ity, can respond only in a limited number of ways to a multi referring physician about invasive diagnostic or therapeutic in
tude of diseases. For example, a number of heavy metals result terventions (e.g., surgery). The final decision about the neces
in primary axonal degeneration. The electrodiagnostic find sity of a surgical procedure rests solely with the referring
ings appears the same, regardless of the particular toxin. In surgeon once the pertinent infonnation has been conveyed.
this instance, the practitioner should inform the referring
physician about the potential toxins or other diseases that may Hard Copies of Waveforms
present in a similar fashion. The history and physical exami A good practice is to obtain a printout of each wavefonn for
nation are of paramount importance in deciding the possibili every stimulus site. This approach allows one to document ade
ties consistent with the electrical findings. Although the quately that every nerve stated in the report was examined. The
impression may not narrow the list to a single diagnosis, at benefit to the practitioner becomes clear when a waveform's
times it guides the referring physician in the proper direction morphology must be reviewed, particularly for comparisons
by suggesting a number of disorders and appropriate confir with waveforms from a previous examination. The waveform
matory laboratory tests. must be accurately designated at the time of the examination to
It is perfectly appropriate for the practitioner to provide the ensure accurate identification. Most instruments provide a quick
referring physician with some idea of the severity of the pathol and pennanent reproduction of the wavefonn, important para
ogy affecting the neuromuscular system. For example, in carpal meters, and recording settings with the option to name it. Some
tunnel syndrome a statement about the degree of involvement of instruments store both the electrically induced waveforms and
the sensory or motor fibers is of value. A mild prolongation of the needle examination as part of the stored report in digital
sensory fibers alone with minimal conduction block may sug fonnat for complete electronic retrieval.
gest a somewhat different therapeutic intervention than absence
of a sensory response and a prolonged motor potential.
Additionally, some indication of prognosis can often be pro EXAMPLES OF ELECTRODIAGNOSTIC
vided once the full extent of the lesion is known. MEDICINE CONSULTATIONS
Clinical Impression. The patient may present with a history
and physical examination suspicious for a particular disease that The examples below illustrate only one of many ways in
is confinned by the electrodiagnostic medicine consultation. which the practitioner can convey the necessary information.
Chapter 14 THE ELECTRODIAGNOSTIC MEDICINE CONSULTATION - 519
A few of the most expensive instruments allow the practitioner Nerve DSL SAmp DML MAmp NCV
to program individualized consultations through the use of a (ms) (JIV) (ms) (mV) (mls)
"report generation" program. As long as the essential elements LMedian 3.2 10.0 Absent
of the electrodiagnostic medicine examination are contained (2nd digit)
in the report, the final format is solely the practitioner's LMedian 3.3 9.0
choice. (3rd digit)
For discussion purposes, a number of less than ideal reports L Ulnar 3.2 35 Absent
are also included. Examining faulty consultations permits an in L Radial 3.4 10.0
vestigation of what constitutes an adequate consultation. For in LAxillary 6.5 1.0
structors responsible for training physicians to become expert in L Musculocutaneous 7.5 O.S
the performance of the electrodiagnostic consultations and RMedian 3.3 40.0 3.7 7.0 59.0
physicians presently in a training program, faulty reports are an (2nd digit)
invaluable teaching tool. RMedian 3.1 45.0
(3rd digit)
EXAMPLE I R Ulnar 3.0 32.0 2.5 6.5 62.0
R Radial 3.0 2S.0
Referring Physician: M.D. R Axillary 3.5 2.5
Referring Diagnosis. Left brachial plexus injury R Musculocutaneous 4.1 3.2
History. The patient is a 40-year-old woman who sustained DSL: distal sensory latency; S Amp: sensory amplitude; DML:
a fall onto her left shoulder after being thrown from a moving distal motor latency; M Amp: motor amplitude; NCV: nerve
vehicle 1 year before the consultation. After this incident, the conduction velocity; ms: milliseconds; IlV: microvolts; m V:
patient states that she can no longer move her entire left arm. millivolts; m/s: meter/second. Motor and sensory amplitudes
Additionally. the patient complains of painful spontaneous sen are measured baseline-to-peak. Sensory latencies are measured
sations radiating into the affected upper limb from the supra to peak and motor latencies to initial negative onset.
clavicular region. Over the past year the pain has improved Needle Electromyography. A needle electromyographic in
somewhat, as has her strength proximal to the elbow, but her vestigation is performed on the left upper limb using a dispos
distal forearm remains numb and weak. She also notes pain in able monopolar needle.
her posterior shoulder region but denies cervical pain, either Muscle Rest Activity Recruitment
spontaneous or initiated by particular movements. The only ab PSW!Fibrillation
normality after the motor vehicle accident was the inability to Supraspinatus o Normal
use the left arm. No other associated injuries or cognitive Serratus anterior o Normal
deficits were noted. The patient is quite distressed about the in Deltoid 2+ Reduced
ability to use her left hand and the arm pain, and she has diffi Biceps brachii 3+ (small amplitude) Moderately reduced
culty sleeping. Triceps 3+ (small amplitude) Markedly reduced
This patient has a history of illicit intravenous drug use and Pronator teres 3+ (small amplitude) Markedly reduced
bilateral salpingo-oophorectomy and is presently taking Pre Extensor 3+ (small amplitude) Absent
marin. She smokes approximately 1 pack of cigarettes per day communis
and drinks at least a six-pack of beer per day. Brachioradialis 3+ (small amplitude) Moderately reduced
Physical Examination. The patient is presently in no First dorsal 3+ (small amplitude) Absent
acute distress and appears generally healthy. Tenderness is interosseous
noted over the left trapezius to palpation with no abnormali Abductor pollicis 3+ (small amplitude) Absent
ties in cervical range of motion. Cervical nerve root traction brevis
signs are negative. The left upper limb reveals gross wasting Pronator quadratus 3+ (small amplitude) Absent
of the following muscles: deltoid, biceps brachii, triceps, ab C5~7 paraspinals 0 Normal
ductor pollicis brevis, and all remaining hand intrinsics. The CS-Tl paraspinals 2+ Markedly reduced
left shoulder demonstrates 160° of forward flexion, 30° of ex After examination of the above musculature, the patient
ternal rotation, 40° of internal rotation, and 145 0 of abduc requests that the examination be terminated. The designa
tion. Decreased tone is noted throughout the left upper limb. tion of small amplitude equates to < 100 IN.
Mild contractures of the left finger flexors and hand intrinsic Summary of Findings
muscles are observed. No pain is noted on passive range of 1. The sensory latencies for the above nerves are normal.
motion of the left upper limb. Sensation is decreased to 2. The sensory amplitudes for the left median and radial
painful stimuli as well as light touch in the left arm in the fol nerves are reduced compared with the right 1imb, whereas the
lowing distribution: anterolateral aspect of the forearm, pos ulnar sensory amplitudes for both limbs are comparable.
terior aspect of the forearm, dorsum of the hand, medial 3. Amplitudes and latencies for the left compared with right
region of the forearm, and volar surface of the hand. Manual axillary and musculocutaneous nerves are reduced and pro
muscle testing demonstrated a 2+/5 grade of strength in the longed, respectively.
left deltoid and biceps brachii; all remaining muscles yield a 4. The motor evoked responses for the left median and ulnar
0/5 grade of strength. The right upper limb demonstrates no nerves are absent.
abnormalities on physical examination. 5. Profound denervation of a long-standing nature is noted in
Nerve Conduction Studies. Nerve conduction studies are the designated musculature with fibrillation potentials and posi
performed in the upper limbs bilaterally. The mid-palm tem tive sharp waves of reduced amplitude.
perature is noted to be 32.5°C on the right and 33°C on the 6. A number of muscles reveal absent or markedly reduced
left. recruitment.
520 - PART III PATIENT CARE-RELATED ISSUES
Eled:rodiagnostic Impression avulsed. Prognosis for recovery is poor. On the other hand, the
1. The above findings reveal complete Wallerian degenera sensory responses for the affected median and radial nerves
tion of the nerves composed of the C8 and T1 root levels. suggests that axonal loss is distal to the nerve root level (i.e.,
Absent motor evoked responses, no voluntary motor units in distal to the dorsal root ganglion). Needle EMG findings reveal
any of the C8ffl muscles examined, and a normal ulnar sensory a pattern of abnormality consistent with a lesion in continuity
response at approximately I year after the injury suggest a C8 of the posterior and lateral cords. The sensory fibers contained
and Tl root avulsion. in the median nerve originate from C6 (second digit) and C7
2. A combination of normal upper cervical paraspinal mus (third digit), which is consistent with the above sensory and
cles, serratus anterior, and supraspinatus muscles with abnormal motor findings. The Erb's point stimulation findings are to be
ities in the biceps brachii, triceps, and pronator teres muscles expected at 1 year after injury. The prolonged latencies suggest
impies a lateral and posterior cord lesion in continuity. significant axonal loss with Wallerian degeneration and regen
Clinical Impression eration. The regenerated nerves have less than adequate myelin
1. The patient most likely suffers from a chronic pain syn and are smaller in diameter; thus, they required a compara
drome, as evidenced by her level of discomfort and difficulty tively longer time to conduct over the same distance as the non
sleeping. affected side.
2. Myofascial pain syndrome in musculature about affected Obviously the patient suffers from the sequelae of a dynamic
shoulder girdle. muscle imbalance about the affected shoulder girdle. The inter
3. The patient appears to be concerned about functional action between fully and partially innervated muscles produces
return in her hand intrinsic muscles. unbalanced forces about the shoulder. A consequence of this
Recommendations muscle imbalance is the generation of myofascial pain, in addi
1. Because the patient most likely has a C8ffl root avulsion tion to possible neuropathic pain from the nerve injury. Pain
and prognosis for functional return of hand intrinsic use is negatively affects the patient's ability to sleep, which in tum re
poor, one may wish to explain fully the consequences of the duces coping skills and functional capacity. Strong considera
above findings and explore various options for compensatory tion should be given to a comprehensive approach to physical
measures. A directed occupational therapy program may be of and mental status, particularly as it relates to pain. One also
benefit. should consider the functional status of the patient, which can
2. A comprehensive interdisciplinary pain clinic evaluation best be determined by an occupational therapist's evaluation of
may help the patient's pain complaints and sleep disturbance. how the patient compensates in activities of daily living.
The above recommendations are made with the patient's best
Comment interest in mind. The practitioner must know the source of the re
The above electrodiagnostic medicine consultation is di ferral to provide a number of recommendations without being
rected at evaluating the functional electrophysiologic status of perceived as attempting to take over the patient's management,
the brachial plexus injury that occurred approximately 1 year unless specifically requested to do so. If possible, it is a good
before the consultation. One certainly could have investigated idea to discuss verbally the complex management of individual
more muscles on needle electromyography to confirm the im patients with the referring doctor. One also may wish to consider
pression. In the authors' experience, once the patient requests meeting with the physicians before performing electrodiagnostic
that the examination be terminated, such wishes should be hon medicine consultations to arrive at a mutual understanding of
ored. There is certainly room for negotiation if 1 or 2 more mus what services the practitioner can provide.
cles or nerves would add significantly to the diagnosis; Mention is made of using a disposable needle electrode in the
however, the patient ultimately must control the decision to ter introduction of the needle EMG portion of the investigation. The
minate an examination. It is the physician's responsibility to quality of modem manufactured disposable needles is very good
inform the patient of what is known at that point so that the pa and continues to improve. Provided a good source is found, the
tient can make an informed decision. Some patients may not tol authors have been quite satisfied with the results obtained with
erate the electrical aspect of the examination but do quite well disposable needle electrodes for routine examinations.
during needle electromyography or vice versa. One may wish to
finish the portion of the test causing patient discomfort and to EXAMPLE 2
offer the other investigation. In any event, the patient is ulti
mately in control of what can be performed. Fortunately, Referring Physician: M.D.
enough information was obtained in the above examination to Referring Diagnosis. Right ulnar neuropathy
comment intelligently on both electrical and clinical findings. History. A 24-year-old, left-hand dominant man sustained
The nerve conduction data were significant for absent motor complete laceration of the right ulnar nerve just distal to the
responses in the median- and ulnar-innervated hand intrinsic elbow after a motor vehicle accident 6 months before the evalu
muscles combined with no voluntary motor units on the needle ation. Approximately 4 months ago, a delayed repair was per
EMG examination. The lack of any motor evoked potentials im formed on the nerve. The patient denies any pain involving the
plies complete Wallerian degeneration of the motor fibers con affected limb and reports absence of sensation along the medial
tained in the median and ulnar nerves. The absence of voluntary aspect of the hand and fifth digit. Additionally, the patient notes
motor units with profound membrane instability on needle significant difficulty in gripping objects with the affected hand.
EMG is consistent with total Wallerian degeneration or signifi A home program to maintain flexibility of the hand and avoid
cant conduction block and severance of at least a portion of the contractures is being performed.
nerve. The motor conduction studies confirm that the C8/Tl The patient denies use of any medication, does not smoke,
motor fibers are nonexistent. A symmetric ulnar sensory re and drinks no alcohol. Aside from the difficulty with gripping
sponse with the asymptomatic limb, combined with no motor objects, the patient denies any other medical problems and is in
responses, strongly suggests that the C8/Tl nerve roots are a good state of general health.
Chapter '4 THE ELECTRODIAGNOSTIC MEDICINE CONSULTATION - 521
Physical Examination. The patient is alert and cooperative some evidence of denervation, and the flexor carpi ulnaris
with all aspects of the history and physical examination. Mild muscle is completely normal.
clawing of the right fourth and fifth digits is noted along with Impression. The electrodiagnostic medicine findings are
significant atrophy of the first dorsal interosseous and hy consistent with complete wallerian degeneration of the ulnar
pothenar eminence. Wasting of the remaining interossei mus nerve supplying the ulnar hand intrinsic muscles with no evi
cles is also noted. All major joints proximal to the wrist dence of reinnervation at this time. Innervation of the flexor dig
demonstrate a full range of active motion. The wrist, metacar itorum profundus is only partially compromised with evidence
pophalangeal, and interphalangeal joints reveal no evidence of reduced but present voluntary motor units. The flexor carpi
of decreased passive range of motion. Sensation is absent to ulnaris appears normal.
both touch and pin-prick in the cutaneous distribution of the Recommendation
right ulnar nerve. Sensibility in the remaining aspects of the I. Repeat electrodiagnostic studies in approximately 4-6
upper limb is normal. Manual muscle testing reveals a 0/5 months to evaluate progression of reinnervation.
grade of strength for the first dorsal interosseous and abduc
tor digiti minimi muscles. Thumb abduction is 4/5 as are the Comment
long finger flexors and extensors. Strength testing in the left The above example is a relatively straightforward study de
upper limb is 515. Deep tendon reflexes of the biceps brachii, signed primarily to evaluate the dynamic physiologic status of
triceps, brachioradialis, and pronator teres are 2+12+ and the ulnar nerve. The total absence of an evoked motor response
symmetric bilaterally. is significant because it indicates the lack of any sparing of
Nerve Conduction Studies. Nerve conduction studies are motor fibers to the hypothenar muscles. Although not all of the
performed in the upper limbs bilaterally. The mid-palm temper muscle compriSing the hypothenar eminence were examined,
ature is noted to be 31.7°C on the right and 32°C on the left. the clinical examination combined with the needle investigation
Nerve DSL S Amp DML M Amp NCV of the abductor digiti minimi muscle allows one to assume that
(ms) (JlV) (ms) (mV) (mls) all muscles most likely share the same functional status. With
R Median 3.0 60.0 2.3 13.0 56.0 sparing of the opponens digiti minimi or flexor digiti minimi, a
R Ulnar Absent Absent small volume conducted response most likely would have been
R Dorsal Absent detected on neural stimulation. The absence of voluntary motor
Ulnar Cutaneous units in the first dorsal interosseous muscle confirms the suspi
L Ulnar 2.9 50.0 2.3 12.0 58.0 cion of complete Wallerian degeneration of the hand intrinsic
L Dorsal 2.3 19.0 muscles innervated by the ulnar nerve. Neural conduction stud
Ulnar Cutaneous ies reveal that the digital sensory fibers are equally compro
L Median 3.2 68.0 2.5 1l.0 55.0 mised to a severe degree, supporting the impression of complete
DSL: distal sensory latency; S Amp: sensory amplitude; DML: loss of motor and sensory ulnar nerve innervation to the hand.
distal motor latency; M Amp: motor amplitude; NCV: nerve Of importance is the finding of an absent dorsal ulnar cutaneous
conduction velocity; ms: milliseconds; ~V: microvolts; mY: nerve response. The lesion, with respect to the sensory compo
millivolts; m/s: meter/second. Motor and sensory amplitudes nent, is proximal to the origin of this nerve and has not reinner
are measured baseline-to-peak. Sensory latencies are measured vated the dorsal aspect of the hand.
to peak and motor latencies to initial negative onset. As a minor digression, it is important to emphasize the clini
Needle Electromyography. A needle EMG investigation is cal utility of the dorsal ulnar cutaneous nerve. Because it arises
performed on the right upper limb using a disposable monopo approximately 8-10 cm proximal to the ulnar styloid,29 this
lar needle. nerve provides a good anatomic landmark with respect to lesion
Muscle Rest Activity Recruitment location. Clinically, if the patient complains of absence of sen
PSW!Fibrillation sation to the medial aspect of the dorsal portion of the hand, a
First dorsal 4+ Absent lesion affecting the ulnar nerve is proximal to the origin of this
interosseous nerve. If the dorsal ulnar cutaneous response is absent, a similar
Abductor digit 4+ Absent conc1usion can be drawn. In the above case, the nerve's re
minimi sponse is unobtainable but present on the other side. We can
Flexor digitorum 1+ Reduced conclude that the lesion is significant and proximal to the origin
profundus of this nerve. It is important to document the presence of the
Flexor carpi ulnaris o Normal dorsal ulnar cutaneous nerve's response on the contralateral
Pronator teres o Normal limb to ensure that proper technique is applied and that the
Abductor pollicis o Normal nerve is truly absent on the affected side (not a result of techni
brevis cal error). The dorsal ulnar cutaneous nerve can be quite a chal
Pronator quadratus 0 Normal lenge to obtain in some persons, and a normal response from the
Summary of Findings opposite limb suggests that the response on the affected side is
I. Absent right ulnar nerve motor and sensory responses to absent secondary to pathology.
the fifth digit and dorsal ulnar cutaneous nerve. The needle EMG investigation suggests that the lesion is at or
2. Normal left median and ulnar motor and sensory responses. just distal to the separation of the fasciculi to the flexor digito
3. Right median nerve displays normal neural conduction for rum profundus, which demonstrates some evidence of denerva
both sensory and motor fibers. tion as well as the presence of voluntary motor units. The flexor
4. Needle EMG reveals an absence of voluntary motor units carpi ulnaris is completely normal. A few median-innervated
in the first dorsal interosseous and abductor digit minimi with muscles were also examined to confirm that the lesion is local
evidence of significant membrane instability. The flexor digito ized to the ulnar nerve. The pronator teres is normal, confirming
rum profundus muscle demonstrates voluntary motor units with that the lesion did not extend proximal to the elbow region to
Sll - PART III PATIENT CARE-RELATED ISSUES
affect the median nerve. The distal innervated median muscles Comment
verify preservation of the motor fibers of this nerve. Median The above report is an example of what some referring physi
neural conduction is also normal. cians may receive after an electrodiagnostic medicine request.
At this point we may comment on the lack of description with This type of note is frequently hand-written with little or no or
respect to "insertional activity." This somewhat controversial ganization, and no dictated report is provided with significantly
designation conveys no additional information beyond reporting more detail at a later time. This type of report calls into q",es
"unsustained trains of positive sharp waves" in the category tion, from the referring physician's standpoint, the practitioner's
"Rest Activity." Additionally, no comment is made about the competence. The above report has so many errors that it is diffi
number of polyphasic motor unit action potentials or motor unit cult to pick a starting point.
action potential amplitude and duration. Essentially, the para Obviously, the history is totally inadequate and begs the
meters referring to motor unit characteristics, such as duration, question whether the practitioner matriculated through a credi
amplitude, and phasicity, are best categorized as "quantitative ble medical school, let alone gained expertise in electrodiagnos
needle electromyography." "Qualitative" quantification of tic medicine. We are completely unaware of the nature,
motor unit action potential parameters is inappropriate because duration, and exacerbating conditions associated with the pa
it can be misleading and inaccurate. Unless a trigger and delay tient's back pain. There is no mention of pain location in the
line are meticulously used, one cannot be certain whether a back region (side or radiation into a limb). The information
motor unit potential is a single potential or the result of super about progression and functional compromise is understandably
imposition of multiple motor unit action potentials. When sev important. In short, the first line of this report cannot be called a
eral motor unit potentials fire independently, they are easy to history. Unfortunately, the physical examination is equally lack
superimpose. These two or more motor units appear with a ing. Manual muscle testing and sensibility examination are not
greater duration and number of phases because of electronic noted. Clearly little time or effort was given to the basic diag
summation. It is impossible to separate single motor units that nostic aspects of performing a history and physical examina
are abnormal from those that are normal but simply superim tion. Similar findings are to be anticipated for the remainder of
posed with neighboring motor units. Additionally, it is inappro the investigation.
priate to use reference tables for motor unit duration and Absolutely no neural conduction studies were attempted. A
amplitude unless the filter and gain settings are reproduced. good practice is to perform a few basic nerve conductions in at
Because the reference values for duration were derived using a least one lower limb to assess the status of the peripheral nervous
low-frequency filter of 2 Hz, whereas most practitioners use a system, which may affect the findings as whole. For example, a
low-frequency filter of at least 8 and up to 15 or 20 times this sural nerve and peroneal or tibial motor nerve conduction should
value, the "normal" motor unit potential duration values no be studied. This study affords the opportunity to evaluate the
longer apply. The same comments apply to amplitude. There presence of a sensory or sensorimotor peripheral neuropathy or
fore, semiquantitative analysis of the motor unit action potential peroneal neuropathy with numbness mimicking radiculopathy.
parameters "on the fly" with a freely running sweep or "freez The importance of substantiating the physiologic status of the
ing" of the screen is less than optimal and does not allow quan peripheral nervous system lies in the fact that the needle EMG
titative statements about the motor unit potentials. aspect of the examination is influenced by the peripheral nervous
The above two reports use a column referred to as "Recruit system's function. An axonal peripheral neuropathy as well as a
ment," which implies the orderly and sequential firing of motor radiculopathy may generate a reduced recruitment pattern, evi
units with increasing force production and must be distin dence of muscular denervation, and signs of reinnervation, such
guished from the needle EMG interference pattern. Recruitment as long-duration polyphasic motor unit potentials. In a patient
can be normal (full), increased, or decreased. Normal recruit with possible neural impingement in the back, these considera
ment means that for a given level of patient effort, an appropri tions are obviously crucial. Evaluation of an H-reflex is also a
ate number of motor units fire at anticipated rates. Reduced good idea in patients suspected of proximal neurophysiologic
recruitment means that fewer-than-anticipated motor units fire compromise, especially lesions involving the S 1 nerve root.
at very rapid rates. On the other hand, increased recruitment The needle EMG examination leaves much to be desired. We
(early recruitment) refers to multiple motor units at low levels have no idea which muscles were examined, including the
of force that fire at relatively rapid rates. Reduced recruitment paraspinal region. The report comments that the patient had an
can be seen in patients with peripheral nerve or anterior hom increased number of polyphasic motor units in the L5 myotome.
cell disease, whereas increased recruitment may be detected in As previously stated, it is inappropriate to comment on polypha
clinically significant myopathic conditions. sic motor unit action potentials unless a trigger and delay line
are used to evaluate single motor units. This report is an attempt
UNACCEPTABLE CONSULTATIONS to appear quantitative when indeed it is not. No mention is made
of positive sharp waves or fibrillation potentials, which are the
Example I foundation of attempting to define the presence of a lesion pro
History. The patient is a 55-year-old man with a complaint ducing Wallerian degeneration of the peripheral nervous sys
of low back pain. MRI shows a centrally located defect at the tem. If one is to make a diagnosis of chronic radiculopathy in
L5level. patients with a slowly progressive lesion with de nervation of
Physical Examination. Deep tendon reflexes of the patella muscle fibers and successful collateral sprouting, it is necessary
are 2+/2+; the Achilles tendon reflexes are 012+ on the left and to use a quantitative approach and measure at least 20 motor
2+12+ on the right. Straight leg raising is positive in both lower unit action potentials with respect to duration, amplitude, and
limbs. phases.
EMG. EMG of the right lower limb revealed an increased Finally, the report states that a "herniated disc" is present.
number of polyphasic motor unit potentials in the L5 myotome. This conclusion is erroneous because the electrical testing per
Impression. Right L5 herniated disc. formed cannot "see" into the patient and identify exactly what
Chapter 14 THE ELECTRODIAGNOSTIC MEDICINE CONSULTATION - 523
material may be damaging a nerve root. For the sake of argu Comment
ment, let us assume that a herniated disc was indeed applying Despite an attempt to do a somewhat credible evaluation, this
compressive force of a magnitude sufficient to produce axonal consultation falls far short of performing the minimal studies
loss. The needle EMG examination would demonstrate evi necessary to assist the referring physician. A more detailed his
dence of denervation only in the muscle examined, albeit in a tory of the patient's weakness needs to be pursued. Certainly a
myotomal distribution. The actual lesion, however, may be a number of possibilities must be explored regarding the distribu
number of other entities, such as tumor, vascular proliferation, tion of the weakness (i.e., primarily proximal about the shoulder
syrinx, or osteophyte. It is appropriate, therefore, to note that a and pelvic girdles). A family history may be of benefit. The pos
radiculopathy may be present and to list a number of causes sibility of muscle pain and other medications is also important.
consistent with the history and physical examination. The final A less than optimal history provides little guidance for the re
diagnosis noted above appears to be based on the MRI as op mainder of the examination. It is unclear why the patient was
posed to the history, physical examination, and electrodiagnos referred for an electrodiagnostic evaluation and what is being
tic findings. Because the history, physical examination, and considered.
electrodiagnostic studies are inadequate, one can only conclude The physical examination lacks both depth and breadth. The
that the MRI was used inappropriately to bias the electrical find notation of weakness must be quantified to achieve a better idea
ings. What little is present of the physical examination suggests of the actual distribution and severity of weakness. Muscle bulk
that there may be neurophysiologic compromise of the left S I and strength should be mentioned. Of particular interest is the
nerve root because of the absent ankle deep tendon reflex, but assessment of muscle function about the anterior and posterior
this is only speculation. cervical regions. The comment about sensation merely states
As noted in the first two examples, the investigated nerves that it is intact. It is unclear whether both the upper and lower
and muscles must be clearly delineated. A tabular format detail limbs were examined as well as the thorax. No mention is made
ing latencies, amplitudes, and velocities is a necessity for neural of muscular tone, pathologic reflexes, or spasticity. The history
conduction studies. For needle electromyography, a list of the and physical leave too many questions and suggest a number of
muscles for a particular limb should be included. Next to each diagnostic possibilities that must be examined.
muscle some indication of electrical activity noted at rest and on The patient's history suggests proximal weakness associated
voluntary contraction is mandatory. Finally, the electrodiagnos with vision abnormalities. In a 35-year-old woman a few of the
tic diagnosis should be based not only on the electrical findings more obvious diagnostic possibilities include myopathy (e.g.,
obtained from nerve and muscle but also on the history and polymyositis or a familial type), neuromuscular junction defect
physical examination. (e.g. myasthenia gravis or medication), peripheral neuropathy
(e.g., chronic inflammatory demyelinating polyneuropathy),
Example 2 and central nervous system diseases (e.g., multifocal demyeli
History. A 35-year-old woman complains of progressive nating type, such as multiple sclerosis). A more carefully per
difficulty with ambulation for the past 7 months. The patient formed history and physical examination may provide
states that she has difficulty arising from the commode and significant assistance in narrowing the causes to be evaluated as
combing her hair. For the past 3 months blurry vision has been part of the electrodiagnostic medicine consultation.
noted. The patient has a history of hypertension and is taking Given the above possibilities, a few more peripheral neural
appropriate medication. conductions should have been performed. Although the nerve
Physical Examination. The patient demonstrates normal conduction velocities appear within acceptable parameters, no
and symmetric deep tendon reflexes. She appears to be slightly mention is made of the proximal appearance or amplitude of the
to moderately weak about the shoulders and hips bilaterally. evoked compound muscle action potentials. A significant reduc
Sensation is intact. tion in amplitude or temporal dispersion would certainly raise
Nerve Conduction Studies. Nerve conduction studies were the possibility of segmental demyelinating regions affecting the
performed in the right upper limb. peripheral nervous system. In addition, sensory nerve action po
Nerve DSL S Amp DML MAmp NCV tentials were not attempted, thereby eliminating a significant
(ms) (flV) (ms) (mV) (m/s) amount of information about the physiologic status of the pe
R Median Not 3.3 11.0 52.0 ripheral nervous system. Serious consideration should have
Performed been given to the evaluation of proximal conduction through the
R Ulnar Not 3.1 9.0 59.0 peripheral nervous system by examining F-waves in a number
Performed of muscles. A total lack of lower limb motor or sensory nerve
R Ulnar Pre-Ex Post-Ex 1 Min 3 Min 5 Min investigations is also a significant omission. Motor and sensory
% Decrement Post Ex Post Ex Post Ex responses in addition to F-waves would have been of significant
5.0 0.0 2.0 7.0 8.0 help in completely evaluating the dynamic physiologic status of
Needle Electromyography. A needle electromyographic in both axons and myelin of the peripheral nervous system.
vestigation was performed on the right upper limb using a stan The neural conduction portion of the consultation indicates
dard monopolar needle. that this practitioner considered a neuromuscular junction
Muscle Rest Activity Recruitment defect as the cause of the patient's weakness. Unfortunately,
R Abductor digit minimi 0 Normal only one muscle was examined-and it was a distal muscle.
R Abductor poUicis brevis 0 Normal Because the decrement was less than 10%, we must assume that
Impression. Normal electrodiagnostic medicine findings on it was considered insignificant; therefore, the study was re
examination today. There does not appear to be a peripheral ported as normal. The decrement that is present, up to 8% at 5
neuropathy or myopathy to account for the patient's weakness. minutes, is certainly suspicious. It is important to recall two im
Repetitive nerve stimulation does not reveal a neuromuscular portant aspects of investigating the possibility of a neuromuscu
junction defect. lar junction defect. First, temperature is a crucial parameter to
524 - PART III PATIENT CARE-RELATED ISSUES
monitor and maintain in the physiologic range of> 32-33°C on If repetitive stimulation had been performed on the ulnar
the surface of the skin over the examined muscle. A decreased nerve with a limb temperature of 33-34°C, a 15% decrement
temperature can effectively repair or minimize the decrement would have been noted. Similar studies of the more proximal
resulting from repetitive stimulation. Secondly, distal muscles muscles also revealed significant decrements. Needle EMG ex
are characteristically less sensitive in detecting a decrement to amination showed motor unit action potentials with acceptable
repetitive stimulation even in the face of a neuromuscular junc durations and amplitudes as well as recruitment, but some
tion defect. In this patient, it is important to note and document demonstrated variability in the more proximal muscles. A more
the surface temperature of the investigated muscle. In addition, complete neural conduction evaluation did not demonstrate evi
more than a single muscle should receive repetitive stimulation. dence of segmental demyelination, and F-wave latencies were
It is necessary to perform repetitive stimulation on a shoulder normal. After appropriate treatment for a neuromuscular junc
girdle muscle, such as the deltoid, biceps brachii, or trapezius, tion defect, the visual disturbances improved.
and possibly a facial muscle, such as the nasalis. Although the
more proximal muscles are more difficult to stabilize, this is no
excuse not to attempt a study; appropriate efforts should be FORMULATING AN APPROACH
made to achieve some level of stabilization. It is also reasonable
to consider exciting one or more lower limb muscles repeti Most patients present with common complaints generated by
tively. Fortunately, the examiner extended the study of the ulnar common problems. As reported by one practitioner, the follow
nerve to 5 minutes, looking for the possibility of postactivation ing electrodiagnostic medicine impressions were documented
exhaustion. It is significant, however, that immediately after ex over the course of one year: lumbar radiculopathy (27%); cervi
ercise there is a repair of a less than diagnostic decrement with cal radiculopathy (16%); polyneuropathy (15%); carpal tunnel
increasing decrement to 5 minutes. This trend is certainly suspi syndrome (10%); other mononeuropathy (9%); myopathy (8%);
cious and suggests that more than one muscle must be exam motor neuron disease (6%); neuromuscular junction defect
ined. One must not forget that the amplitude of the muscle (4%); and plexopathy (2%).1 Aside from a few highly special
response immediately after exercise may show little decrement, ized clinics, most electrodiagnostic medicine laboratories prob
but it should be compared with the muscle's amplitude before ably have a similar patient population. The electrodiagnostic
exercise. This comparison may suggest a significant repair, even medicine expert must be prepared to pursue rare entities if the
though the expected potential decrement is absent. Additionally, occasion arises. The practitioner must be thoroughly familiar
the compound muscle action potential's amplitude at 5 minutes with the various presentations of diseases affecting the neuro
must be compared to the amplitude before exercise to consider muscular system as well as with neuromuscular anatomy and its
the possibility of a pre-exercise to post-exercise decrement, possible variations.
even though a decrement is not noted within a train of five stim Unlike an EKG or EEG, the electrodiagnostic medicine con
uli. In short, more than just one muscle should have been inves sultation cannot be standardized and performed completely by a
tigated with repetitive stimulation. technician, no matter how well trained. The dynamic nature of
The needle EMG examination was inadequate for a patient the findings as they unfold during an examination may require
who complains of upper and lower limb weakness. The proxi examination of unanticipated nerves or muscles, particularly in
mal muscles on one side of the body should have been exam the presence of unusual disease presentations, anatomic vari
ined as well as a few distal muscles of the lower limb. In this ants, or technical artifacts. Flexibility and expertise in disease
patient, it is necessary to perform a quantitative needle exami presentation are the keys to performing the electrodiagnostic
nation using the appropriate low filter settings as well as a trig medicine consultation.
ger and delay line for individual assessment of 20 different Most patients present with a complaint of pain, weakness,
motor unit action potentials with respect to amplitude, dura numbness, or some combination of the above. Given the
tion, and phases. The duration values must be compared with common electrodiagnostic medicine impressions, the following
standard reference tables. The possibility of early recruitment discussion is provided not as a "cookbook" approach to per
is also of concern. The same procedure should be considered forming a consultation but as a beginning point for the novice
with several proximal and distal muscles of the upper and practitioner. Once the approach for a general problem is initi
lower limbs on one side of the body. Motor units also must be ated, the guiding principle is to be ready to proceed in whatever
examined with respect to stability (i.e., their appearance from direction the data direct, as dictated by the practitioner's med
one firing to the next). If a neuromuscular junction defect is ical knowledge and expertise.
present, the affected muscles may show motor units that
change amplitude and duration from one firing to the next be THE PAINFUL UPPER LlMBAND CERVICAL REGION
cause single muscle fibers comprising the motor units block
and no longer contribute to the summated voltage. It is neces Let us assume that a patient presents with a complaint of pain
sary to specify which limbs were examined so that the needle affecting a single upper limb and did not experience obvious lo
trauma does not yield artifacts that may interfere with a muscle calized or diffuse trauma. A well-directed history and physical
biopsy interpretation. examination have been performed. In most cases, these two im
Finally, because the patient complains of vision disturbances, portant portions of the consultation provide enough information
one must evaluate the visual pathways. Consideration should be to perform a limited number of appropriate investigations to di
given to visual evoked potentials. Of course, if a proper history agnose the patient's problem. Occasionally, diffuse pain with
and physical examination had been performed originally, the few localizing symptoms or signs affects the limb, raising a
number of necessary studies would be significantly reduced. number of diagnostic possibilities. One of the more common
The impression formulated by this practitioner is wholly unsub diseases that may result in upper limb pain is radiculopathy.
stantiated because an insufficient number of nerves and muscles Cervical nerve roots C6 and C7 tend to be affected more often
were examined. than C5 or C8!f1. 32 The most common mononeuropathy examined
Chapter 14 THE ELECTRODIAGNOSTIC MEDICINE CONSULTATION - 525
by most practitioners is carpal tunnel syndrome. Additionally, site for possible median nerve entrapment. If the time across the
ulnar nerve compromise at the elbow should be kept in mind. A proximal 7-cm segment is less than across the distal 7-cm seg
rare but important consideration for unilateral ann pain is idio ment, it is unlikely that the fibers innervating the third digit are
pathic brachial neuritis. Generalized polyneuropathy or myopa compromised about the carpal tunnel. Of course, it may be pos
thy is unlikely to present with unilateral ann pain. sible to affect median sensory fibers preferentially to the first or
second digit in isolation, particularly early in the disease course.
NEURAL CONDUCTION On the other hand, if the latency across the proximal segment
equals or exceeds that of the distal portion, entrapment of the
Median Nerve. In evaluating the painful upper limb, the median nerve about the carpal tunnel should be considered.
authors prefers to begin with median nerve conduction evalua Both of the above situations can occur with absolute 14 cm la
tions for both motor and sensory portions of the median nerve tencies completely within the nonnal range. For example, let us
(Table 14-1). The sensory component of the median nerve is assume that the patient has a 14-cm median sensory latency of
usually evaluated with an antidromic technique at 7 cm and 14 3.4 ms (nonnal < 3.6 ms) and a 7-cm latency of 1.6 ms. The
cm from the third digit, although the second digit may be used time across the carpal tunnel region is 1.8 ms, implying that
just as easily. The rationale for the two stimuli is to detennine a conduction is preferentially slowed through the carpal tunnel. If
split time across the carpal tunnel region, which is a common the 14-cm latency is "abnonnal" but the time across the carpal
526 - PART III PATIENT CARE-RELATED ISSUES
tunnel is less than the distal latency, it is necessary to consider a frame of Wallerian degeneration and neural inexcitabiJity after
distal neuropathy affecting the median nerve, in which case a trauma. Finally, F-waves may be of assistance in defining a prox
more generalized process should be sought, or the hand may be imal compromise of the motor nerves if distal findings are mini
cold. It is mandatory to record the temperature about the record mal, as may occur in Guillain-Barre syndrome.
ing electrodes, especially in the limbs. In addition to latency, Ulnar Nerve. Once the median nerve has been evaluated, it is
one also must assess the sensory response amplitude. The 7-cm a good idea to continue to the ulnar nerve. If we assume u~nar
segment waveform should be about 10-20% larger than the sensory responses are to be pursued initially, the ulnar nerve is
wrist response because of less temporal dispersion with the stimulated 14 cm proximal to the E- 1 recording electrode on the
stimulus site closer to the recording electrode. 34 If the amplitude fifth digit for an antidromic technique. This response may be af
at 14 cm approaches 50% or less than the 7-cm segment, a con fected by a generalized process or two common localized sites of
duction block most likely exists at the wrist. This amplitude entrapment in the limb (i.e., wrist and elbow). Of course, we are
change mayor may not occur with concomitant latency alter assuming no obvious sites of pathology, such as a traumatic
ations. Unfortunately, sensory amplitude values decrease as the brachial plexus injury (see above). When a generalized process
distance between recording and stimulation sites increases. It is suspected, the median as well as lower limb nerves must be
may be perfectly normal for a response obtained with wrist examined. The two mononeuropathies that can involve the ulnar
stimulation to be significantly reduced when the median nerve nerve are lesions about the elbow (e.g., cubital tunnel) and wrist
at the antecubital fossa is excited. Both amplitUde and area de (e.g., canal of Guyon). Defining a canal of Guyon lesion can be
crease because of phase cancellation secondary to temporal dis rather difficult and requires the assistance of motor studies as
persion. If such conditions arise or findings with the above well as needle electromyography. It is important also to investi
techniques are in doubt, additional studies (e.g., orthodromic gate the dorsal ulnar cutaneous nerve by recording this response
sensory, mixed nerve responses) can be performed.27 from the dorsum of the hand while stimulating the ulnar nerve
When obvious trauma is present, such as brachial plexopa proximally. A normal dorsal ulnar cutaneous nerve response
thy, two distinct sensory responses are anticipated. If the lesion with an abnormal digital response suggests that a lesion involv
is proximal to the dorsal root ganglion, the median responses to ing the ulnar sensory fibers is present distal to the origin of the
the first and second digits (C6: upper trunk; lateral cord; dorsal ulnar cutaneous nerve and helps eliminate the elbow
median nerve) or third digit (C7: middle trunk; lateral cord; region as a possible lesion site. If the ulnar nerve is affected at
median nerve) are spared and of normal amplitude and latency. the elbow region, it is possible in selected cases to arrive at a
On the other hand, a postganglionic lesion at the trunk, cord, or pure sensory conduction of ulnar nerve fibers as they traverse the
peripheral nerve level results in a diminished sensory nerve ulnar groove. In this instance, it is necessary to record a response
action potential. In suspected brachial plexus lesions, it is nec from all stimulation sites (e.g., 4 cm distal and 10 cm proximal
essary to examine the sensory response of the second and third to the medial epicondyle) and to measure the waveform to the re
digits for the anatomic pathways conveying C6 and C7 sensory sponse's departure from the baseline as opposed to peak latency.
fibers. Averaging may be necessary as the response declines precipi
The median nerve compound muscle action potential latency tously with progressively more proximal stimulation sites. As for
and amplitude also should be investigated. Prolongation of the the median nerve, proximal sensory amplitudes over relatively
distal motor latency can occur in a localized entrapment at the long interstimulus distances are of minimal diagnostic signifi
wrist or secondary to a dying back-type of neuropathy. If either cance because of temporal dispersion and phase cancellation.
the motor or sensory responses are prolonged, additional nerves It is possible to calculate conduction velocities across the
must be investigated to confirm a generalized process. The elbow region as well as latency differences within the hand for
nificance of amplitude can be a bit confusing, depending on the ulnar nerve motor fibers. In considering ulnar groove lesions,
time frame of the investigation with respect to onset of the dis the segmental conduction may help to assess focal conduction
ease process. Within the first several weeks after a profound block or slowing secondary to demyelination. Because temporal
injury to the median nerve, the compound muscle action poten dispersion and phase cancellation are comparatively less for
tial declines commensurately with the number ofaxons lost. motor responses, amplitude is of greater value than sensory
Comparison of the unaffected and injured sides allows a rough wavefonns. In lesions about the wrist, one can evaluate latency
estimate of the amount of axonal loss by calculating a side-to differences between the compound muscle action potential as
side decrement: (amplitude (good side] - amplitude [bad side] .; recorded from the abductor digit minimi and first dorsal in
amplitude (good sideD x 100 =percent axonal loss. Within about terosseous muscles. 21 This approach may be of some help in a
4-6 weeks, however, collateral spouts from intact axons begin to lesion preferentially affecting the deep branch of the ulnar nerve
innervate the denervated muscle fibers and enlarge the number distal to the innervation of the abductor digit minimi.
of muscle fibers per motor unit. 11 The side-to-side amplitude dif Radial Nerve. The easiest aspect of the radial nerve to ex
ference then begins to diminish, and an accurate estimate of amine is the superficial sensory branch. A superficial radial
axonal loss can no longer be performed. 7 If a peripheral nerve nerve response can best be recorded with an electrode posi
lesion is suspected at a particular site, it is a good idea to attempt tioned over the nerve fibers as they cross the tendon of the ex
to stimulate above and below the injury to investigate the possi tensor pollicis longus muscle just distal to the wriSt. 18 This
bility of a conduction block. A small-amplitude proximal stimu nerve is important because it is spared with involvement at
lation, combined with a lager-amplitude stimulation distal to the common entrapment sites; it is located more proximally and
presumed site of damage (recording distally), suggests a conduc thus less subject to temperature fluctuations. It has been recom
tion block with the potential of good recovery of involved fibers. mended as a good comparison with the median nerve when
Of course, this finding implies sufficient time for axonal degen carpal tunnel syndrome is a consideration. 14 A delay of the
eration (i.e., 3-5 days after injury).'o Stimulating above and median compared with radial peak response by 0.5 ms or more
below a complete neural transection within the first several days suggests preferential compromise of the median nerve at the
may reveal little if any amplitude difference because of the time carpal tunneL
Chapter 14 THE ELECTRODIAGNOSTIC MEDICINE CONSULTATION - 527
Table 14·2. Painful Lower Limb and Related Low Back Region
Neural conduction
Peroneal motor: I. Stimulation of the peroneal nerve at the ankle (8 cm) proximal to EDB and distal to fibular head.
2. If suspect lesion at fibular head; stimulate above and below fibular head for both EDB and TA recording
sites.
3. Compare above results with similar stimuli on contralateral limb.
Peroneal sensory: I. Stimulate 12 cm proximal to ankle recording site.
2. Lesion proximal to dorsal root ganglion should not affect response.
3. If response abnormal; consider lesion distal to dorsal root ganglion and compare with contralateral
limb.
Tibial nerve: I. Stimulate tibial nerve posterior to medial malleolus 8 cm proximal to recording site over AH.
2. If root lesion or other proximal pathology suspected examine bilateral H-reflexes.
3. When foot pain is present mixed medial and lateral planter nerves excited on plantar surface of foot
with recording over tibial nerve at ankle can help.
Sural nerve: I. Record posterior to lateral malleolus and stimulate 14 cm proximal on midline of posterior leg.
2. May need to average response. Should be normal in lesion proximal to dorsal root ganglion. If absent,
consider lesion distal to dorsal root ganglion.
Femoral nerve: I. For localized femoral nerve pathology, excitation of the femoral nerve in the inguinal region with
recording from the vastus medialis can be performed.
Plexopathy: I. Can perform L5 and S1 nerve root stimulation combined with sciatic nerve excitation in attempt to
calculate conduction across sacral plexus. Similar technique for lumbar plexus by activating L3-4 nerve
roots combined with femoral nerve excitation.
Needle electromyography
Easily examined muscles I. Lumbosacral paras pinal muscles
2. Gluteus maximus (inferior gluteal N; L5. S I-S2)
3. Tensor fascia lata (superior gluteal N; L4-S I)
4. Vastus medialis (femoral N; L2-4)
5. Tibialis anterior (peroneal N; L4-5)
6. Tibialis posterior (tibial N; L5-S I)
7. Medial gastrocnemius (tibial N; S I-S2)
Abnormalities See Table I
SeeTable I
These suggestions are only generalizations. Specific lesions should be pursued with a well-directed consultation. Any combination of the above may be used in an in
dividual patient, or additional specialized techniques may be necessary, depending on the problem investigated. ED8: extensor digitorum brevis;AH: abductor hallucis;
TA: tibialis anterior. Modified from Albers JW: Common EMG problems. In AAEM Course k. Fundamentals of EMG (Fifth Annual Continuing Education Course).
Rochester. MN, 1982. pp 59-67, with permission.
Motor responses are significantly more difficult to obtain in the Needle Electromyography
radial nerve than for the ulnar or median nerve, primarily because Insertion of a needle electrode (monopolar or concentric con
the radial muscles used for recording purposes are localized within figuration) into muscle tissue with the intent of recording spon
the distal forearm. When the radial nerve is excited, especially taneous activity (normal and abnormal) as well as voluntary
proximally, volume-conducted responses from all of the excited motor units provides perhaps the most sensitive demonstration
muscle are recorded and amplitude becomes highly unreliable. As of axonal loss. In patients with a painful upper limb, it is impor
a result. needle recording electrodes are recommended for docu tant to examine muscles representative of the anterior and pos
menting latencies. Of course. amplitude is of little significance terior primary cervical rami. Posterior primary rami innervate
under such circumstances. In short, the radial motor response is the paraspinal muscles. In the cervical region, paraspinal mus
usually attempted only when a preferential lesion affecting the cles innervated by the medial branches of the posterior primary
radial nerve is suspected by history or physical examination. rami (deep unisegmentally innervated layer, representing roots
AdditionaJ Stndies. Whenever a generalized process is sus C4 through T1) can be easily investigated. A needle electrode
pected. one must consider examining the lower limbs to docu should be placed about 1 cm lateral and 1 cm inferior to the cor
ment the extent of the lesion and diagnose the full range of responding spinous process, inserted until the lamina are en
nerves affected as well as to fonnulate a prognosis for potential countered, and then withdrawn a few millimeters. Complete
problems likely to emerge in the future. If common entrapment relaxation is mandatory to observe spontaneous activity, which
neuropathies are found. serious consideration should be given may require proper positioning of the patient. In the upper limb,
to exploring the existence of these lesions in the opposite limb. nerve roots C5-Tl are represented by various muscles in the
Both carpal tunnel and ulnar neuropathies at the elbow can be limb and shoulder girdle. It is important to study at least two
noted in the contralateral limb. If a plexopathy is documented, different muscles innervated by separate nerves for each root
neural conduction through the axillary, musculocutaneous, or level. For example, in considering C51C6 root levels, the
other proximal nerves can be perfonned. 16 Both side-to-side supraspinatus (C5IC6; suprascapular nerve; upper trunk), del
amplitude and latencies are considered. If intramuscular needle toid (C5IC6; axillary nerve; upper trunk; posterior cord), and
placement is necessary (e.g .• suprascapular or long thoracic biceps brachii (C5IC6; musculocutaneous nerve; upper trunk;
nerves), only latency is assessed. lateral cord) muscles can be examined. This same principle can
528 - PART III PATIENT CARE-RELATED ISSUES
be applied for each root level and trunk/cords of the brachial from the abductor hallucis muscle. Again, a standard distance of
plexus. 8 cm proximal to the recording site on the muscle helps to min
Because of the discomfort often associated with needle exam imize intertrial variation with respect to distal motor latency. In
ination, one may wish to consider performing it after the nerve patients who complain of foot pain, one should consider the
conduction aspect of the consultation has been completed. Some possibility of tarsal tunnel syndrome. Perhaps the most reliable
patients, however, prefer needle insertion to neural excitation, technique of evaluating the medial and lateral plantar nerv~s is
and the examiner must remain flexible to meet the patient's to record the mixed nerve action potential of the tibial nerve at
needs. It is probably wise to initiate the needle examination in the ankle while stimulating the nerves in the plantar aspect of
the proximal portion of the limb and progress to the hand, which the foot. 24 This method is significantly more amenable to study
is more sensitive. One may wish to finish the investigation by in than attempting to record the pure digital sensory responses,
vestigating the cervical paraspinal muscles. which are extremely small and unreliably obtained in normal
people. Additionally, the mixed nerve response appears to be
THE PAINFUL LOWER LIMB AND LOW BACK REGION more sensitive to neural compromise than the motor evoked po
tentials to the abductor hallucis and abductor digit quinti mus
An electrodiagnostic medicine consultation of lower limb or cles. Finally, if an Sl radiculopathy is considered the cause of
low back pain is similar to that previously described for upper low back or limb pain, an H-reflex can easily be performed on
limb pain. Essentially, one must be concerned with evaluating both lower limbs as recorded from the gastrocnemius-soleus
the possibility of a radiculopathy, plexopathy, or focal mono muscle complex. As with the peroneal nerve, tibial nerve F
neuropathy (Table 14-2). The referring physician's consultation waves can be attempted and may be of benefit in lesions affect
is of great help, but the complete electrodiagnostic consultation ing the proximal portion of the nervous system.
relies primarily on the history and physical examination. The Sural Nerve. A highly reliable sensory nerve in the lower
referring consultation provides focus on the chief complaint and limb is the sural nerve, as recorded posterior to the lateral malle
reason for referral. olus when the nerve is excited 14 cm proximal to this site in the
middle of the leg. 25 A lesion affecting preferentially the S 1
Neural Conduction nerve root proximal to its dorsal root ganglion should not alter
Peroneal Nerve. A convenient place to begin the lower limb the sural nerve waveform. Plexopathies, sciatic nerve injuries,
examination is with the motor component of the peroneal nerve. or distal tibial (and possibly peroneal) mononeuropathies may
The compound muscle action potential to the extensor digitorum alter the sural nerve response. The sural nerve is rarely involved
brevis following stimulation of the peroneal nerve at the ankle in a localized entrapment neuropathy but is more likely to be in
and below the fibular head typically yields good responses. For jured by trauma.
consistency, the author prefers a standard 8-cm distance between Femoral Nerve. Occasionally, one may detect preferential
the E-l recording site and the cathode for the distal site for weakness of the knee extensors. Such weakness may occur sec
recording a distal motor latency. If a lesion at the fibular head ondary to an inguinal lesion or lumbar plexopathy or diabetic
may be the cause of foot drop, one must consider exciting the per amyotrophy. The femoral nerve can be stimulated at the in
oneal nerve both above and below the fibular head. The reason guinal region just lateral to the femoral artery while recording
for performing this type of stimulation is to assess the presence of from the vastus medialis muscle. 13 A second stimulus may be
conduction block or demyelination as the nerve is commonly applied several centimeters proximal to the inguinal activation
compromised about the fibular head. 30 In this instance, the ampli site.
tudes above and below the fibular head are compared, and con Additional Studies. When a plexopathy is seriously consid
duction velocity is determined. The proximal stimulation is a bit ered, the practitioner can calculate the conduction across the
tricky because the nerve is commonly rather deep and must be lumbosacral plexus by stimulating the appropriate nerve root
stimulated medial to the tendon of the biceps femoris at or just and peripheral nerve. 19 In the case of a lumbar plexopathy, a
proximal to the popliteal fossa. Care must be exercised to avoid recording can be performed from the vastus medialis muscle
simultaneous activation of the tibial nerve, thus generating a while stimulating the L3-4 nerve roots and femoral nerve.
volume-conducted response in the foot. It is also a good idea to Subtracting the two conduction times yields a conduction time
record from the tibialis anterior muscle, because weakness of this across the lumbar plexus. Similarly, activating the L5 and Sl
muscle is the cause of foot drop. Whenever a unilateral lesion of nerve roots and sciatic nerve in the gluteal fold while recording
the peroneal nerve is suspected, the other side should be exam from the abductor hallucis or gastrocnemius muscles can pro
ined to gain some idea about the degree of axonal loss or conduc vide a transplexus conduction time.
tion block. In addition to the motor component, one should
investigate the sensory aspect of the peroneal nerve. Stimulating Needle Electromyography
the superficial sensory peroneal nerve approximately 12 cm prox As for the upper limb, it is necessary to examine muscles in
imal to the ankle usually generates an easily detectable response nervated by both the anterior and posterior primary rami. In
when recording from the distal sensory branches at the ankle considering the posterior primary rami-innervated muscles, the
region.12 Lesions proximal to the dorsal root ganglion presenting deep paraspinal muscles (multifidi) must be investigated. This
with a foot drop (e.g., L5 radiculopathy) should not alter the su can be accomplished by inserting a needle electrode about 1-2
perficial sensory peroneal nerve response, whereas injury distal cm lateral to the spinous process for a given bony level, contact
to the dorsal root ganglion may well compromise this response. ing the lamina, and then withdrawing a few millimeters. If a
Occasionally F-waves may be of assistance, although these wave particular level is suspected, that level plus at least one segment
forms are usually associated with other abnormalities and are not above and below should be examined. If membrane instability
particularly sensitive locators of pathology. is noted at any level, paraspinallevels need to be investigated
Tibial Nerve. The tibial nerve is rather easy to examine and until an absence of abnormality is documented to appreciate
typically produces rather large motor responses when recorded fully the extent of the injury. A number of lower limb muscles
Chapter 14 THE ELECTRODIAGNOSTIC MEDICINE CONSULTATION - 529
can be examined to explore all aspects of the root distributions, parameters include not only conduction velocity but also wave
lumbosacral plexus, and peripheral nerve innervation. A few form amplitude, duration, and morphology. Preferential in
muscles to consider include the gluteus maximus (inferior volvement of motor, sensory, or both types of fibers is rather
gluteal nerve; LS, SI-S2), tensor fascia lata (superior gluteal obvious once the data have been collected. If the neural conduc
nerve; L4--S1), vastus medialis (femoral nerve; L2-L4), tibialis tion velocity is rather slow « 70-75% of lower range of
anterior (peroneal nerve; L4-LS), tibialis posterior (tibial nerve; normal), serious consideration should be given to a demyelinat
LS---5I, medial gastrocnemius (tibial nerve; SI-S2). If there is ing component affecting the nerves. On the other hand, if the
uncertainty about a particular nerve root level or peripheral amplitudes are significantly reduced, a loss ofaxons is most
nerve distribution, additional muscles from the same root or likely present. Should a low-amplitude, slowly conducting po
nerve can be examined as well as the same root level of a differ tential be identified, one should suspect a combination of de
ent peripheral nerve. For example, if an L2 root lesion is sus myelination and axonal loss.
pected, one can explore not only the vastus medialis muscle but Occasionally one may encounter a distal evoked waveform
also the iliopsoas and adductor longus muscles, thus consider with a relatively normal distal motor latency and amplitude, but
ing two muscles containing L2 root innervation but different pe proximal stimulation reveals a waveform that is highly polypha
ripheral nerve supplies. If an S-2 lesion is in the differential sic with a markedly prolonged duration. This finding suggests a
diagnosis, the external anal sphincter may be of assistance. As segmental demyelinating lesion with a differential effect on the
always, the contralateral limb should be considered when posi conduction velocity of the affected fibers. Because the fibers are
tive findings are noted to exclude the possibility of a bilateral slowed in a nonuniform manner, a significant amount of tempo
problem. ral dispersion is induced, and the range of conduction velocities
is markedly increased. This increased range of conduction is re
PERIPHERAL POLYNEUROPATHY flected in the evoked response as a reduction in amplitude and
an increase in duration and number of phases. Profound ampli
Patients believed to have a generalized peripheral neuropathy tude reduction and temporal dispersion also may indicate that a
based on history and physical examination combined with labo concomitant conduction block is present. It may not be a simple
ratory data (e.g., blood glucose level) usually do not present a task to distinguish the degree of conduction block from segmen
diagnostic challenge. In this instance, the most important aspect tal slowing with respect to amplitude reduction. 23 One also may
of the eJectrodiagnostic medicine consultation is not to diagnose note a preferential prolongation of the distal motor latencies
a peripheral neuropathy but to document its extent and severity. only. In this instance, a so-called "dying-back" neuropathy may
On the other hand, the investigation is much more difficult be manifesting at a relatively early stage. Enough nerves from
when the patient is referred for a diffuse complaint of pain or multiple limbs should be investigated to clearly differentiate
numbness in no particular distribution. It then becomes neces between a generalized process versus multiple mononeu
sary to document fully not only the presence and extent of gen ropathies (see Table 14-3). The full extent of the individual
eralized peripheral nerve involvement but also the type of nerve involvement can be determined only by collecting the
neuropathy (axonal, demyelinating, or combined) and its sever data and continuously evaluating what additional studies are
ity. The practitioner must offer a number of possible diseases most appropriate to help define the chief complaint and dura
that may be the cause of the patient's complaints based on his tion of neural involvement.
tory and physical examination. It also may be helpful to suggest Lower Limb. In the lower limb a number of nerves must be
a number of laboratory tests that may help confirm the electro evaluated to assess the extent of peripheral nerve compromise.
diagnostic impression. A relatively common situation is the pa If the distal responses are absent, it is necessary to progress to
tient who complains of a focal neurologic problem, such as more proximal muscles innervated by the nerve of interest or to
carpal tunnel syndrome, but in reality has a generalized periph examine a totally different nerve at a more proximal location.
eral nerve compromise secondary to a diffuse disease process Essentially the same nerves are examined as for investigating
with a number of superimposed entrapment neuropathies. a painful lower limb. The peroneal motor and sural sensory re
In evaluating a patient suspected of having a peripheral neu sponses are usually sufficient to appreciate the extent to which
ropathy, it is important to characterize the primary manner in the peripheral nerves are affected. If the peroneal nerve-evoked
which the nerves are affected. Specifically, is the pathology in response is relatively small and demonstrates significant slowing
juring the nerves preferentially damaging the myelin, axon, or of neural conduction associated with a prolonged sural nerve la
both? A second distinction to be made is whether motor nerves, tency and reduced amplitude, the beginning of a sensorimotor
sensory nerves, or a combination of both is predominantly in peripheral neuropathy with both demyelinating and axonal com
volved (Table 14-3). This information can help to classify the ponents is suggested. An upper limb and possibly the other lower
various types of peripheral neuropathies and assist in diagnos limb should be examined to confirm this initial impression. If, on
ing a particular disease. 5 the other hand, the peroneal and sural nerves are absent and there
is little clinical suspicion of a mononeuropathy, multiplex pattern,
Neural Conduction the tibial nerve and peroneal conduction to the tibialis anterior
Most peripheral neuropathies affect lower limb nerves before muscle must be considered. A saphenous conduction with mid
upper limb nerves. Additionally, sensory fibers are affected knee stimulation and mid-leg recording also may be attempted to
before or in association with motor fibers but typically to a examine a more proximal sensory nerve. The extent to which
greater degree. Rarely, motor fibers may be predominantly in more proximal conductions are attempted is determined by the
volved, but there is usually some minor degree of sensory in successful recording of a response. In this way, the progression
volvement as well. Because peripheral neuropathies tend to be and severity of the peripheral neuropathy emerge. If a patient
generalized but somewhat asymmetric, it may be necessary to presents with primarily burning feet and the sural and peroneal
investigate both lower limbs with respect to motor and sensory nerves are unaffected, the practitioner can pursue a more distal
conduction. The primary characteristics of neural conduction neural evaluation. The medial and lateral plantar mixed-nerve
530 - PART III PATIENT CARE-RELATED ISSUES
2. Abnormal proximal limb muscles, examine paraspinal muscles, trapezius muscle, and facial muscles.
3. abnormalities, sWdies on contralateral limb.
EDB: extensor digitorum brevis.AH: abductor hallucis. TA: tibialis anterior. ADM: abductor digiti minimi. These suggestions are only generalizations. Specific lesions
ShOI r!d be pursued with a well-directed consultation. Any combination of the above may be used in an individual patient, or additional specialized techniques may be
necessary. depending on the problem investigated. Modified from Albers JW: Common EMG problems. In AAEM Course A: Fundamentals of EMG (Fifth Annual
Continuing Education Course). Rochester. MN. 1982. pp 59-67, with permission.
responses can be examined quite easily and may be a more sen axonal loss does not yield demonstrable findings with respect to
sitive indicator of pathology in an early neuropathy that has not membrane instability (positive sharp waves/fibrillation poten
progressed as far proximal as the ankle. Caution must be exer tials) or motor unit action potential abnormalities. There may be
cised, however, because these nerves are occasionally prone to an increase in the number of polyphasic potentials secondary to
compression in the tarsal tunnel region. Bilateral absence of demyelination of the terminal axons, however, thus decreasing
these responses may allow serious consideration of a more gen the synchronicity of single muscle fiber depolarizations within a
eralized problem as opposed to localized entrapments. given motor unit. Recruitment may be abnormal in purely de
Upper Limb. The same nerves considered for the painful myelinating lesions if conduction block has affected the motor
upper limb are investigated when peripheral polyneuropathy is nerves. In axonal loss lesions, one can gain an appreciation of
suspected. The more distal nerves are explored before examin the duration of neural involvement. The appearance of recruit
ing more proximal conduction. If the upper limbs are pro ment abnormalities without positive sharp waves or fibrillation
foundly affected, the facial nerve may be assessed to determine potentials and concomitant alterations in motor unit action po
whether the disease process has progressed to involve the facial tential morphology suggests a number of possibilities. The
structures. Whenever a peripheral neuropathy is suspected, the lesion may have jt'st occurred, and there is insufficient time for
practitioner must be cognizant of coexistent entrapment axonal loss and accompanying Wallerian degeneration to mani
mononeuropathies. Compromised nerves suffering from a gen fest as membrane instability. In the authors' opinion, subtle or
eralized disease process may be more prone to the common minor lesions producing axonal loss do not result in detectable
compression sites such as the carpal tunnel or ulnar neu recruitment abnormalities even if positive sharp waves and fib
ropathies at the elbow. The radial nerve is relatively free of en rillation potentials are observed. Noticeable alteration in recruit
trapment and offers a good alternative to neural conduction ment intervals indicate that a substantial lesion is present. In the
when median or ulnar compression is suspected. above scenario, if axonal loss has resulted, positive sharp waves
and fibrillations appear within 2-3 weeks. The amplitude of
Needle Electromyography these potentials may reach several hundred microvolts. On the
The needle EMG examination is of primary value in peripheral other hand, if recruitment abnormalities are noted acutely after
neuropathies with axonal loss. Demyelination without substantial injury, the nervous system may be suffering from a temporary
Chapter 14 THE ELECTRODIAGNOSTIC MEDICINE CONSULTATION - 531
conduction block. In this instance, recovery may be significant, A much more systematic approach can be taken when weak
and recruitment patterns can return to normal within several ness arises from an abnormality of the lower motor neuron. It is
weeks with little if any development of membrane instability. helpful to consider the concept of the motor unit in attempting
Detection of recruitment abnormalities, positive sharp waves to define pathologic involvement of the peripheral neuromuscu
and fibrillation potentials of about 100 IlV or less and a few lar system. For our purposes, the motor unit may be defined as
large-amplitude and long-duration motor units suggests that the the anterior horn cell, axon, and all of the single muscle fibers
lesion was of a profound nature and is now in the old and healed innervated by that anterior hom cell. Included in this definition
or chronic (slowly progressing) stage. Small-amplitude positive are the neuromuscular junctions associated with each muscle
sharp waves and fibrillation potentials imply that the muscle fiber. Progressing from the anterior horn cell distally, one may
fibers have undergone significant atrophy and subsequently consider the following anatomic structures to be potentially af
generate only small amplitude potentials. 17 In addition, large fected by a particular disease: anterior hom cell (motor neuron
amplitude, long-duration motor unit potentials signify that the diseases), nerve root (radiculopathy), plexus (plexopathies), pe
motor unit has undergone reorganization at the single-fiber level ripheral nerve (peripheral neuropathies andlor entrapment
through collateral sprouting. This process requires several mononeuropathies), neuromuscular junction (myasthenia
months to complete. One must use careful quantitative tech gravis, myasthenic syndrome, etc.) and muscle fiber (my
niques with a trigger and delay line before concluding that an opathies). This list of possible lesion sites often helps to suggest
abnormal amount of polyphasic motor unit potentials is present. a number of potential disease states.
Between these two extremes, a range of abnormalities can be When the presenting problem is weakness, it is first neces
demonstrated, indicating that a neural lesion is in transition be sary to perform a few preliminary investigations to gather suffi
tween the acute and chronic stage. cient data to formulate an approach that is diagnostically fruitful
Lower Limb. Generally, a few distal and proximal muscles and efficient (Table 14-4). This discussion assumes that, despite
warrant examination to investigate the presence of muscle find a detailed and directed history and physical examination, a
ings noted above with respect to spontaneous activity at rest and number of possibilities may account for the clinical presenta
recruitment. A few recommended muscles include the gastroc tion, or sufficient doubt remains in the practitioner's mind that
nemius and tibialis anterior muscles distally and the vastus me it is best to pursue initially a generalized investigation.
dialis and tensor fascia lata muscles proximally. The paraspinal Occasionally, it is best not to form a preconceived notion about
muscles (L51S1 and Ll1L2) are also of importance in defining a the diagnosis and to remain open to the data as they unfold.
polyradiculoneuropathy. Examining these muscles bilaterally After a number of possibilities are eliminated through neural
helps to define the extent of the potential lesion if findings are testing, a more focused examination can be undertaken.
abnormal on a particular side. If these muscle are normal and Let us assume that a clear diagnosis does not present itself after
the clinical situation is suspicious for a distal problem, the ab a history and physical examination have been performed. It is usu
ductor hallucis may be examined, but it must be kept in mind ally a good idea to begin with assessment of the peripheral ner
that a proportion of normal persons can demonstrate positive vous system's sensory component (see Table 14-4). If the patient
sharp waves and fibrillation potentials in these muscles. states that a particular limb is involved, it is preferable to begin the
Upper Limb. The same recommendation applies to the electrodiagnostic medicine evaluation with this limb. If no particu
upper limb that was noted for the lower limb-Le., a few distal lar limb appears to be affected, the lower limbs are a good begin
and proximal muscles are investigated. The first dorsal in ning point. Because most diffuse disease processes affect the
terosseous, pronator teres, and biceps brachii are examples. If lower limb sensory nerves first, a better appreciation of neural in
any abnormalities are noted, the same muscles on the contralat volvement can be gained with a sural nerve evaluation. Because
erallimb should be examined. If findings suggest axonal loss to the presenting symptom is weakness, it is also necessary to con
the level of the proximal arm, needle examination of the cranial sider peroneal motor conduction. If the weakness is located proxi
muscles (e.g., nasalis, masseter, and tongue) and trapezius mus mally, femoral nerve conduction may be of assistance. Certainly
cles are important to define the proximal extent of the disease the same rationale applies to the upper limb regarding motor and
process. sensory studies for proximal and distal problems.
A normal sensory response with little if any abnormality of
DIFFUSE WEAKNESS motor conduction despite demonstrable weakness should raise
the suspicion of a neuromuscular junction disorder or primary
Patients presenting with a chief complaint of generalized muscle disease. Additionally, considerations should be given to
weakness, moderate to minimal poorly localized pain, and little early Guillain-Barre syndrome or systemic illness. Neuro
if any sensory disturbances can be quite a diagnostic challenge muscular junction transmission abnormalities require a repeti
even to the most experienced investigator. Essentially a disease tive stimulation evaluation of both distal and proximal muscles.
affecting any portion of the upper motor neuron or lower motor Primary muscle disorders are best confirmed with needle elec
neuron may be responsible. With respect to upper motor neuron tromyography of both the proximal and distal muscles. Any ab
disorders, one is likely to find physical evidence consistent with normality in the above nerves or muscular regions requires
upper motor neuron signs (e.g., hyperreflexia, spasticity, abnor further detailed analysis to consider specific diseases.
mal reflexes, increased tone), possibly in a distribution sugges
tive of a particular disease. With respect to the electrophysiologic MOTOR NEURON DISORDERS
examination, motor and sensory neural conduction studies are
characteristically normal in all respects. Needle electromyogra Although a number of diseases may affect the anterior hom
phy of the involved muscles may reveal diffuse membrane in cell, perhaps the most familiar is amyotrophic lateral sclerosis
stability for several months that later disappears. 22 The primary (ALS). The hallmarks of ALS are multi focal weakness with
abnormality is an alteration in motor unit action potential re sparing of sensation or only mild sensory compromise. With re
cruitment with poor and irregular firing.4 spect to neural conduction and needle electromyography, rather
532 - PART III PATIENT CARE-RELATED ISSUES
o Examine upper limb sensory nerve: e.g., median sensory to third digit, or ulnar sensory to fifth digit.
I. Upper limb weakness implies motor nerves may be affected, defect in neuromuscular transmission can be present, and a myopathy
is certainly possible.
o Examine ulnar nerve motor conduction to ADM with F-wave analysis.
o Repetitive stimulation of proximal muscles, e.g., excitation of spinal accessory with trapezius muscle recording pre-exercise and
post-exercise looking for decrement. Can also excite musculocutaneous nerve in axilla and record from biceps brachii for
repetitive stimulation.
Abnormality
I. Abnormality noted in one of the above requires more detailed investigation of affected area.
o Peripheral neuropathy requires detailed neural conduction of upper and lower limbs.
o Decrement signifies neuromuscular junction transmission failure and proximal muscles including facial muscles should be inves
tigated.
o Possible radicular pathology requires needle electromyographic analysis.
o Weakness with decreased amplitude of compound muscle action potentials but normal neural conduction of both motor and
sensory fibers should raise suspicion of primary muscle disease and the performance of a detailed quantitative needle elec
tromyographic investigation.
Needle electromyography
I. A few proximal and distal muscle should initially be assessed with particular attention paid to motor unit action potential ampli
tude, duration, phases, and initial recruitment at low levels of force production.
2. When a possible muscle disease is suspected, routine qualitative needle electromyography is insufficient.The practitioner should
use a trigger and delay line with appropriate filter settings to properly analyze the motor unit action potentials for duration (most
sensitive parameter).This cannot not be done on a freely running instrument trace.The data must then be compared with refer
ence data tables.
3. Only one side of the body should be examined so that muscle biopsies can be performed on the other side and be free of needle
artifact.
4. Possible muscle to examine include: biceps brachii, extensor digitorum communis, abductor digit minimi; tibialis anterior, vastus me
dialis, medial gastrocnemius, and gluteus medius. Facial muscles can also be investigated. It is imperative to always examine the
lumbar and cervical paraspinal muscles as these are frequently abnormal in many diseases particularly primary muscle disorders.
EDB: extensor digitorum brevis; ADM: abductor digit minimi;TA tibialis anterior. This table is meant only as a beginning approach and may change as data are ob
tained during the examination. Modified from Albers JW: Common EMG problems. In AAEM Course A Fundamentals of EMG (Fifth Annual Continuing Education
Course). Rochester, MN, 1982, pp 59-67, with permission.
characteristic findings are expected with moderate to severe dis action potential parameters and altered recruitment consistent
ease; somewhat more variable findings can be anticipated with with loss of motor units.
mild disease or at initial presentation (Table 14-5). These four criteria are helpful in attempting to diagnose ALS
Lambert's criteria continue to be useful in attempting to di as long as one keeps in mind that this is the classic presentation;
agnose ALS with electrical testing2: many patients meet some but not all of the above criteria. It may
1. Fibrillation potentials and positive sharp waves (mem require some tim~ for patients to manifest all of these findings.
brane instability, i.e., evidence of denervation) as well as fascic Until that time, clinical suspicion plus what ever findings are
ulations potentials in at least three limbs, with the bulbar muscle present must suffice.
group comprising a "limb." In 1995 revised criteria for the diagnosis of ALS were agreed
2. Sensory nerve conduction parameters within normal limits upon-the EI Escorial criteria. 6 The body is divided into four
for age. regions, and, depending on the extent of upper (UMN) and
3. Motor nerve conduction parameters within normal limits lower motor neuron (LMN) involvement, the patient is catego
for age except when amplitude is abnormal. In this instance, the rized as follows:
conduction velocity should remain above 70% of the mean for Clinically definite ALS is defined by clinical evidence alone
the nerve under study. with UMN and LMN signs in three regions.
4. Findings on needle electromyography suggestive of den Clinically probable ALS is defined by clinical evidence
ervation/reinnervation as evidenced by abnormal motor unit alone with UMN and LMN signs in at least two regions with
Chapter 14 THE ELECTRODIAGNOSTIC MEDICINE CONSULTATION - 533
Needle electromyography
I. The clinical examination should direct the muscle examined with weak or atrophic muscles examined first moving on to less weak mus
cles.
2. Abnormalities (positive sharp waves and fibrillation potentials) should be found in at least 2 muscles with different root and preferably
different peripheral nerve innervation. Head considered as an limb.
3. Should look for chronic neurogenic changes with respect to motor unit action potential parameters and recruitment. These may be
subtle findings in a slowly progressive disease.
4. Closely examine individual motor units for variation in amplitude or morphology with sequential firing as a sign of tenuous neuromuscu
lar junction transmission.
5. Appreciate widespread nature of motor neuron disorders and do not expend undue time investigating clinically uninvolved muscles.
6. Examine bulbar innervated muscles: masseter, tongue (genioglossus), nasalis, and trapezius muscle for example.
This table is meant only as a beginning approach and may change as data are obtained during the examination. Modified from Albers JW: Common EMG problems. In
AAEM Course A: Fundamentals of EMG (Fifth Anllual Continuing Education Course). Rochester, MN, 1982. pp 59-67, with permission.
some UMN signs necessarily rostral to (above) the LMN obtainable sensory potentials in the lower limb simply as a result
signs. of aging. One also must consider that patients with a peripheral
Clinically probable laboratory-supported ALS is defined neuropathy from some unrelated disease process (e.g., diabetes
when clinical signs of UMN and LMN dysfunction are present mellitus) may be affected by ALS, in which case the sensory
in only one region or when UMN signs alone are present in one findings are abnormal. Additionally, because the patient most
region and LMN signs defined by EMG criteria are present in at likely has chronic neurogenic changes secondary to a peripheral
least two limbs, with proper application of neuroimaging and neuropathy, a motor neuron disorder is difficult to discern.
clinical laboratory protocols to exclude other causes. Finally, a small population of patients with true ALS indeed have
Clinically possible ALS is defined when clinical signs of abnormal sensory responses. Certainly histologic evidence sup
UMN and LMN dysfunction are found together in only one ports pathologic involvement of the sensory system.' As a result
region; UMN signs are found alone in two or more regions; or of these potential problems, one cannot always count on the sen
LMN signs are found rostral to UMN signs and the diagnosis of sory response to provide a definitive answer.
clinically probable, laboratory-supported ALS cannot be proved Unless the motor neuron disorder is particularly aggressive
on clinical grounds in conjunction with electrodiagnostic, neu and rapidly progressive, motor conduction should be normal. If,
rophysiologic, neuroimaging, or clinical laboratory studies. on the other hand, there is significant loss of motor neurons, one
Other diagnoses must have been excluded to accept a diagnosis can anticipate that some of the fastest-conducting fibers are lost.
of clinically possible ALS. In this instance, a slowing of conduction is expected, but not
Clinically suspected ALS is a pure LMN syndrome, wherein below 70% of the lower limit of normal values. This slowing
the diagnosis of ALS cannot be regarded as sufficiently certain typically is accompanied by a reduction in the compound
to include the patient in a research study. Hence, this category is muscle action potential amplitude secondary to axonal loss.
deleted from the revised El Escorial Criteria for the Diagnosis Because multifocal motor neuropathy can mimick the clinical
ofALS. signs and symptoms of ALS, it is important to rule out conduc
A patient can move to a more certain category on the basis of tion blocks by measuring the CMAP over nerve segments in re
electrodiagnostic findings. In the electrodiagnostic criteria, gions that are clearly affected with an emphasis on proximal
signs of active (positive sharp waves and fibrillations) and conduction and stimulation. An additional finding with respect
chronic neurogenic features should be present. Chronic neuro to motor conduction is the possibility of mild to moderate
genic changes are defined as large motor unit potentials, re decrement (not greater than 20%) on repetitive nerve stimula
duced interference pattern with firing rates higher than 10Hz, tion studies. A decrement may be present because of an active
and unstable motor units. Supporting the diagnosis is the pres denervating process with collateral sprouts attempting to rein
ence of fasciculation potentials. The abnormalities should be nervate the denervated muscle fibers. For some time after the
sought in four different regions: bulbar (one affected muscle attachment of a newly formed collateral sprout, the neuromus
suffices), thoracic spinal cord region (either paraspinal at or cular transmission is tenuous. This less than stable transmission
below Th6 or in the abdominal muscles), and two affected mus across the immature neuromuscular junction results in intermit
cles in the cervical and lumbosacral spinal cord region (inner tent blocking. with the involved muscle fiber no longer con
vated by different roots and peripheral nerves). Although these tributing voltage to the overall amplitude of the compound
electrophysiologic criteria have been criticized,33 they are now muscle action potential. The end-result is a decrement on repet
applied world-wide. itive stimulation. Postactivation facilitation and exhaustion can
be found in such patients.
Neural Conduction An important concept to keep in mind with respect to both
As noted above, the anticipated findings are normal sensory neural conduction (motor and sensory) and repetitive stimula
potentials in both the upper and lower limb. Unfortunately, a tion studies is the effect of temperature. In patients with chronic
few elderly patients affected by ALS may not have readily neurogenic lesions and muscle loss, the limbs frequently
534 - PART III PATIENT CARE-RELATED ISSUES
become quite cold. It is imperative to maintain the limb at an tip of the mandible. Temporalis and masseter (cranial nerve V)
appropriate temperature to ensure minimal effects of tempera muscles also can be examined. Finally, any of the muscles of
ture on both neural conduction and repetitive stimulation. facial expression are readily accessible to needle insertion.
units. The result of these electrical "gaps" is an increase in the by conventional methods. If a myopathic process preferentially
number of phases or turns per motor unit action potential (I.e., affects type II fibers (e.g., steroid myopathy), the needle EMG
polyphasic motor unit action potentials). The loss of muscle investigation may not reveal abnormalities.
fibers per motor unit also generates a motor unit potential that is
shorter in duration. Because less force is generated per motor NEUROMUSCULAR JUNCTION
unit, more motor units must fire to produce a given amount of TRANSMISSION DISORDERS
force. The recruitment pattern observed in myopathies is, there
fore, an abundance of motor unit action potentials firing faster The most common way to evaluate neuromuscular junction
than anticipated at low levels of force production (so-called transmission is repetitively evoking a compound muscle action
"early recruitment"). At low levels of force, more motor units potential at 2-3 Hz (i.e., repetitive stimulation) (Table 14-7).
than anticipated fire rapidly with reductions in duration and am Successful repetitive stimulation requires patient cooperation
plitude but increases in the numbers of phases. Although it is and minimization of technical artifacts. Unfortunately, repeti
possible for the experienced clinician to gain an impression of tive activation of a peripheral nerve and recording of the ensu
these findings from qualitative needle EMG, quantitative analy ing compound muscle action potential can be somewhat
sis on at least a few of the affected muscles is strongly encour uncomfortable. In attempting to measure the amplitude of suc
aged to document the actual durations of the suspected motor cessive responses within a train of stimuli, it is essential that
units before diagnosing a patient with a myopathy, particularly the baseline be absolutely stable. The stability of the CRT
in mild disease. This is one of the most difficult areas of electro baseline depends directly on the patient's ability to relax and
diagnostic medicine because borderline findings often are en not to react with voluntary muscle contraction during neural
countered and no definite conclusions can be drawn. stimulation. Patient cooperation and relaxation can be achieved
Most primary muscle disorders preferentially involve proxi only if the practitioner completely explains the procedure and
mal muscles; these muscles should be studied, in addition to a the importance of complete relaxation to the success of the
few distal muscles, to gauge the extent of the disease process. study. A poor explanation of the technique invites a challeng
The shoulder girdle and proximal arm muscles are generally in ing study with gain of little useful information. Some patients
vestigated. These muscles can include the supraspinatus or infra simply cannot tolerate the procedure. If it is impossible for the
spinatus, trapezius, deltoid, biceps brachii, and triceps muscles. patient to relax, the investigation should be terminated be
It is also a good idea to examine the pronator teres, extensor dig cause little can be gained by causing undue discomfort. The
itorum communis, and first dorsal interosseous muscles. In the patient can be requested to come back another time or simply
lower limb, one should consider the gluteus medius, vastus me note for the referring physician that the patient cannot tolerate
dialis, tibialis anterior, and gastrocnemius muscles. No consulta the procedure.
tion for a myopathy is complete unless the paraspinal muscles Perhaps the most demanding portion of the repetitive stimu
have been explored in the cervical and lumbosacral regions. lation examination is reducing technical artifact. Voluntary
Consideration also can be given to a few of the thoracic muscle contraction or patient movement can render the data un
paraspinallevels. A few muscles on the contralateral side may be acceptable. Similarly, recording electrodes that are not securely
studied to document the bilateral nature of the disease, but only fastened to the patient can produce significant movement arti
muscles that are not likely to be biopsied should be examined. fact. Recording electrode motion at times can generate a series
The motor units that one can investigate in detail with respect to of waveforms that appear as if a true decremental response is
motor unit action potential parameters are type I fibers because present, creating a false-positive result. The stimulating elec
type II fibers are recruited only after type I fibers. The CRT base trodes also should be fastened to the patient to reduce move
line is usually completely obliterated when type II fibers begin ment. )f the cathode is loose, it may be displaced further from the
firing, thus rendering quantitative analysis essentially impossible nerve with each muscle contraction, thus generating a decremental
536 - PART III PATIENT CARE·RELATED ISSUES
response. Unfortunately, it is not always possible to secure elec In addition to movement, temperature is an important vari
trodes as well as one might wish. Although distal muscles can able to control. A surface temperature that is less than optimal
be secured rather well, their sensitivity is less than that of proxi « 32°C) can have profound affects on the examination. Cool
mal muscles for demonstrating neuromuscular junction trans limbs can result in a repair of the decrement so that a mild se
mission defects. quential decline in amplitUde with successive neural activation
Proximal muscle recordings require stimulation of the pe may be absent in a warmer limb. It is important to recall that
ripheral nervous system at less than ideal locations. For exam during repetitive stimulation of the peripheral nerve, the pa
ple, recording from the deltoid muscle requires the brachial tient's limb can become cool. One must continually monitor
plexus to be excited at Erb's point. This type of stimulation re limb temperature during the repetitive stimulation study to
sults in contraction of the entire arm, producing a significant ensure that a warm limb at the beginning of the study remains
amount of movement. Additionally, it is impossible to immobi so throughout the investigation.
lize the arm completely. In this instance, patient cooperation be The most common type of neuromuscular junction transmis
comes paramount to a successful recording session. The authors sion defect likely to be encountered is myasthenia gravis. This
prefer activation of the spinal accessory nerve while recording postjunctional defect may demonstrate a decremental response
from the trapezius. The patient can sit on the hand to minimize during repetitive stimulation. As noted above, both distal and
movement. A facial muscle is also of importance to attempt proximal muscles need to be examined. A second type of neuro
repetitive stimulation, particularly in a cooperative patient. The muscular junction defect is myasthenic syndrome (Lambert
only way to achieve any type of immobilization of the face is to Eaton syndrome), which is a prejunctional defect. A similar
request the patient to lie perfectly still and attempt not to react study (see below) is performed in these patients as in patients
to facial nerve excitation. suspected of having myasthenia gravis.
Chapter 14 THE ELECTRODIAGNOSTIC MEDICINE CONSULTATION - 537
Lower limb
I. Peroneal motor to EDB and consider TA with across fibular head study especially if foot drop present.
2. Superficial peroneal sensory nerve to evaluate preganglionic versus postganglionic lesion location if clinically indicated, i.e., L5
versus fibular head lesion.
3. Sural nerve response at ankle.
4. Tibial nerve stimulation for leg segment to AH.
5. May consider F-wave latencies to EDB and AH.
Needle electromyography
Upper limb
I. Muscles to examine include deltoid, biceps brachii, triceps, pronator teres, extensor digitorum communis, flexor pollicis longus, ab
ductor pollicis brevis, and C5-T I cervical paraspinal muscles.
Lower limb
I. Muscle to examine include tensor fascia lata (gluteus mediUS), vastus medialis, tibialis anterior, extensor hallucis longus, medial/lat
eral gastrocnemius. and L I-S I paraspinal muscles. Consider external anal sphincter if S2 lesions suspected or to help distinguish
motor neuron disorders.
EDB: extensor digitorum brevis;AH: abductor hallucis;TA: tibialis anterior;ADM: abductor digiti minimi;APB: abductor pollicis brevis. Other muscles on needle elec
tromyography may need to be examined depending upon the clinical findings. This table is meant only as a beginning approach and may change as data are obtained
during the examination. Modified from Albers JW: Common EMG problems. In AAEM Course A: Fundamentals of EMG (Fifth Annual Continuing Education Course).
Rochester, MN, 1982, pp 5~7, with permission.
538 - PART III PATIENT CARE-RELATED ISSUES
neuromuscular junction transmission abnormality suggests that sharp waves and fibrillation potentials in a particular myotomal
single-fiber EMG analysis should be performed. If one does not distribution is helpful in localizing a lesion affecting a given
perform this particular test, the patient should be referred to a nerve root. One also must consider more chronic lesions in
physician who is comfortable with it. Although this test is which the motor unit has been remodeled by collateral sprout
highly sensitive, it is not specific for myasthenia gravis but de ing with the expected alterations in motor unit action potential
tects subtle abnormalities of neuromuscular junction transmis amplitude, duration, and phases. The abnormalities should b~ in
sion failure. Usually the extensor digitorum communis is at least two muscles innervated by two different peripheral
examined as well as a more proximal arm muscle. The facial nerves. Occasionally, particularly in elderly patients, membrane
muscles also can be investigated. instability can be observed in multiple muscles innervated by
more than a single nerve root. In this instance, the normal sen
Needle Examination sory responses may be accompanied by absent or severely re
Although occasional positive sharp waves and fibrillation po duced compound muscle action potentials and positive sharp
tentials can be seen in neuromuscular junction disorders, such waves and fibrillation potentials at several levels in the
findings are typically the exception, not the rule. Membrane in paraspinal region. Disorders such as spinal stenosis, multilevel
stability usually is seen only in severe disease states and signifies osteoarthrosis, lateral recess stenosis, tumor compressing the
that the neuromuscular junction is so disrupted that it is no longer cauda equina, and motor neuron disorders should be considered.
physiologically attached to the muscle fiber. The primary abnor Examination of the rectal sphincter has been recommended to
mality that may be seen with needle EMG is variability of the assist in the diagnosis of motor neuron disease versus multilevel
motor unit from one firing to the next. This variability is best ob radicular involvement because the rectal sphincter should be
served by having the patient fire only one or two motor units normal in the former disease.
(minimal contraction) with a slow sweep speed (e.g., 50 ms/div) Documenting positive sharp waves and fibrillation potentials in
so that a large number of firings of the same motor unit can be ap a myotomal distribution of a magnitude exceeding 100-200 /lV,
preciated on the CRT screen. Using this technique, the changing including the paraspinal muscles, in a patient with a history and
morphology and amplitude of a single motor unit action potential physical examination compatible with a radicular insult suggests
can be appreciated. Alternatively, a trigger and delay line can be axonal loss affecting the implicated nerve roots (i.e., an acute
used to maintain the motor unit potential in the same position and lesion). Observing large-amplitude, long-duration polyphasic
observe changes in amplitude and morphology. The physiologic motor unit action potentials in a myotomal distribution is indica
basis of this phenomenon is the blocking of individual single tive of a healed lesion in which the compensatory mechanism of
muscle fibers that no longer contribute their waveform to the motor unit remodeling has repaired the initial axonal loss. Failing
motor unit potential as a whole, thus generating a slightly differ to detect positive sharp waves and fibrillation potentials, even in
ent appearance with each motor unit discharge. This finding can the presence of "chronic" motor unit changes, results in insuffi
be rather subtle and is best observed in more affected muscles. cient electrophysiologic evidence to diagnose an acute radicular
lesion. Finding increased "polyphasic" motor unit action poten
RADICULOPATHYIPOLYRADICULOPATHY tials, even in a myotomal distribution, is also insufficient evidence
of an ongoing process adversely affecting the nerve root. Far too
Neural Conduction many practitioners believe that abnormal motor unit potentials are
In a disease process that may affect multiple nerve roots in indicative of an acute lesion and justify surgery on this basis. In
nervating either the upper or lower limb, it is important to deter early radicular insults « 3-4 weeks), positive sharp waves and fib
mine initially the status of the peripheral sensory nerve-evoked rillation potentials may be absent despite axonal loss. In this case,
responses (Table 14-8). Normal sensory nerve action potentials failure to document membrane instability is a limitation of the test,
combined with sensory complaints are highly suggestive of a and clinical judgment combined with imaging studies is the most
lesion proximal to the dorsal root ganglion (e.g., a nerve root appropriate diagnostic method.
injury). If a radiculopathy or polyradiculopathy has resulted in Practitioners must understand the progression of radicular le
significant axonal loss, the anticipated effect on motor conduc sions. Most lesions affecting the nerve root, or any other aspect
tion studies is a reduction in the amplitude of the evoked com of the peripheral nervous system for that matter, are dynamic. In
pound muscle action potential. It is unusual for a unilevel other words, there is usually a process whereby the peripheral
radicular lesion to obliterate completely the evoked motor po nerve initially experiences a block of neural conduction before
tential because most muscles are innervated by more than one manifesting other types of abnormality (Table 14-9). This
nerve root. Motor nerve conduction velocities, however, should process has direct effects on the recruitment of voluntary motor
be relatively spared unless there is profound axonal loss at mul units and proximal neural conduction studies. Once axonal loss
tiple levels. Although by no means a particularly sensitive or has occurred, the process of Wallerian degeneration progresses
early finding, F-wave latencies can be prolonged in radicular in to completion in several days and affects the observation of
juries, especially if demyelination has occurred over this region. evoked motor and sensory responses. Depending on the dis
It is possible to investigate H-reflex latencies at selected root tance between the site of injury and muscle tissue, positive
levels. In the upper limb, the flexor carpi radialis H-reflex may sharp waves and fibrillation potentials may be detected in the
assist in the assessment of potential C7 radiculopathies. Lower muscles innervated by the affected nerves in 1-3 weeks.
limb lesions affecting the S 1 nerve root can be evaluated with Approximately 4-6 weeks after injury, collateral sprouting may
the tibial nerve H-reflex to the gastroc-soleus muscles. begin, thus remodeling the motor unit and affecting the morphol
ogy of the voluntary motor unit action potentials. This reinner
Needle Examination vation obviously reduces the amount of membrane instability.
The exploration of muscle tissue with a needle electrode is Once the pathophysiology of this type of injury is understood,
perhaps the most fruitful portion of the electrodiagnostic medicine the practitioner can better approach patients who appear to have
consultation for diagnosing radiculopathies. Detection of positive a unisegmental or multiple-level root injury.
Chapter 14 THE ELECTRODIAGNOSTIC MEDICINE CONSULTATION - 539
positive sharp waves; CRD: complex repetitive discharges; MUAPs: motor unit action potentials. This table is only a rough approximation and may vary with individ.
ual patients.
Modified from Albers JW: Common EMG problems. In AAEM Course A: Fundamentals of EMG (Fifth Annual Continuing Education Course). Rochester, MN, 1982, pp
24. Saeed MA, Gatens PF: Compound nerve action potentials of the medial and lat 29. Sunderland S: Nerves and Nerve Injuries, 2nd ed. Edinburgh. Churchill Living
eral plantar nerves through the tarsal tunnel. Arch Phys Med Rehabil 1982;63: stone, 1978.
304-307. 30. Wilbourn AJ: AAEM Case Report # 12: Common peroneal mononeuropathy at
25. Schuchmann lA: Sural nerve conduction: A standardized technique. Arch Phys the fibular head. Muscle Nerve 1986;9:825-836.
Med RehabiI1977;58:166-168. 31 Wilbourn AJ: The electrodiagnostic examination with myopathies. J Clin
26. Stalberg E, Chu J, Bril V, et al: Automatic analysis of the EMG interference pat Neurophysioll993;10:132-148.
tern. Electroencephalogr Clio NeurophysioI1983;56:672-681. 32. Wilbourn AJ, Aminoff MJ: AAEM Minimonograph #32: The electrophysiologic
27. Stevens JC: The electrodiagnosis of carpal tunnel syndrome. Muscle Nerve examination in patients with radiculopathies. Muscle Nerve 1998;21:1612-1631.
1997;20:1477-1486. 33. W!lbournAJ: Clinical neurophysiology in the diagnosis of amyotrophic lateral sclero
28. Stewart CR, Nandedkar SD, Massey JM, et al: Evaluation of an automatic sis: The Lambert and the EI Escorial criteria. J Neurol Sci 1998;16O(Suppll):S25-29,
method of measuring features of motor unit action potentials. Muscle Nerve 34. Wongsam PE, lohnson EW, Weinerman ID: Carpal tunnel syndrome: Use of
1989;12:141-148. palmar stimulation of sensory fibers. Arch Phys Med RehabilI983;64:16-19.
Chapter 15
Electrodiagnostic Medicine
Pitfalls
Daniel Dumitru, M.D., Ph.D.
Machiel J. Zwarts, M.D., Ph.D.
The perfonnance of electrodiagnostic medicine consultations neuromuscular disease and its electrophysiologic presentation
is well described in this work as well as other textbooks. 51 •60 requires that only persons who are medically trained in the diag
These same books adequately describe the selective perfonnance nosis of these diseases and their electrodiagnostic presentation
of nerve conduction studies (NCS), needle electromyography should perfonn an electrodiagnostic medicine consultation. Lack
(EMG), and somatosensory evoked potentials (SEPs) with re of m~~ u:aming, lack of e~pe~~ in the operation of ~lectro
spect to various clinical situations in which specific techniques phYSiologiC mstruments, and maolhty to collect electrodlagnos
can be used to define more accurately the extent of neuromuscu tic data accurately are a prescription for potential misdiagnoses
lar pathology. Unfortunately, electrodiagnostic medicine pitfalls, and hence possible patient harm. This is likely the most common
of which there are many, rarely receive adequate discussion. The pitfaJJ in electrodiagnostic medicine consultations.
expert practitioner is thoroughly familiar with the most appropri
ate electrodiagnostic techniques to diagnose specific diseases as
well as their potential shortcomings and limitations. This chapter NERVE CONDUCTION STUDIES
examines possible consequences of a less than thorough compre
hension of the more common pitfalls. Although various pitfalls Motor and sensory nerve conduction studies (NCS) are sub
are discussed in detail throughout this text, the most illustrative ject to similar pitfalls. Major potential problem areas are ex
are discussed in a separate chapter to emphasize their importance plored for both motor and sensory NCS; distinctions are drawn
and ease of identification. when appropriate (Table 15-1). The practitioner is advised to
The electrodiagnostic medicine consultation consists of two consider these broad categories whenever perfonning NCS, par
major aspects: (1) a medical history and physical examination ticularly when acquired data do not confonn to anticipated
directed at neuromuscular pathology, and (2) specific electrodi physiologic principles.
agnostic techniques to acquire infonnation about the neuro
physiologic status of nerve and muscle. The combination of INSTRUMENTATION FACTORS
clinical infonnation and electrodiagnostic data, in concert with
expert knowledge about neuromuscular disease pathophysiol A thorough understanding of the electrophysiologic instru
ogy and, if necessary, genetic and/or biopsy studies, results in ment is fundamental to the performance of an accurate and
the medical diagnosis of specific disorders. Therapeutic inter complete electrodiagnostic medicine consultation. Compre
vention is based on the fonnulated diagnosis. The complexity of hensive discussion of the instrument's function is beyond the
541
542 - PART III PATIENT CARE-RELATED ISSUES
Table IS-I. Nerve Conduction Study Pitfalls is placed as close as possible to the electrical activity of interest,
Instrumentation factors whether it arises from nerve or muscle. The reference electrode
Recording electrodes theoretically is located at a place of minimal or no electrical ac
Active/reference electrode location tivity so that the active electrode's electrical signal is "refer
Electrode stability enced" to the "electrically silent" reference electrode. In reality,
Stimulating electrodes there are no places of zero potential on the body after
Stimulus artifact nerve/muscle activation--only more or less location-dependent
Zone of depolarization electrical activity. As a result, the reference electrode theoreti
Anodal block vs. cathodal reversal cally records less of a signal than the active electrode. The fact
Electrode stability that there is no such thing as an electrically silent region on the
Amplification
body is the basis for several potential pitfalls. Both recording
Filters
electrodes are active to varying degrees; hence the preference
Nerve conduction velocity determination
for designations E-J and E-2.
Amplitude variability
Number of stimulation sites ELECTRODE LOCATION
PhySiologic factors The active and reference electrode locations, with respect to
Temperature each other and the electrical activity of interest, are crucial to
Anomalous innervation collecting accurate electrophysiologic data. Convention primar
Age ily dictates "optimal" electrode positioning for both motor and
Gender sensory NCS. The term "optimal" is relative and essentially
Height refers to the manner in which the original investigators first de
Central modulation (Facilitation) scribed or popularized a particular technique. The use of any
previously defined reference database mandates that the initial
defined parameters of data collection must be reproduced.
scope of this chapter (see Chapter 3); however, several instru
mentation factors are pertinent to the discussion ofNCS pitfalls. SENSORY NERVE CONDUCTION STUDIES
Various aspects of the instrument, including recording/stimulat
ing electrodes, filters, and amplification, can contribute to Interelectrode Separation
errors. The more common pitfalls arising from the preceding in The generally accepted separation between the active and ref
strumentation components are described below. erence electrodes for recording antidromic or orthodromic sen
sory nerve action potentials (SNAPs) is 4 cmP This
RECORDING ELECTRODES recommendation is predicated on maximizing the SNAP ampli
tude. Beyond an interelectrode separation of 4 cm, the SNAP
Active and reference electrodes are used to record the electri amplitude, as recorded from most normal persons, no longer
cal activity from nerve and muscle tissues. The active and refer continues to increase appreciably. The rise time (time it takes
ence electrodes are also referred to as the E-! (G-l) and E-2 for the SNAP to reach the negative spike's maximal amplitude)
(G-2) electrodes, respectively.29 The terms E-! and E-2 are pre is about 0.8-1.0 ms. The relationship between interelectrode
ferred because of the lack of an absolute zero potential zone (see separation and maximal amplitude/rise time is based on the
below); this chapter, however, uses the terms active and refer electrical activity recorded by a reference electrode with respect
ence because of convention and familiarity. The active electrode to the active electrode.
A--\---- 0.5 2.8 3.2 8 0.7 0.4 Figure 15-1. Antidromic median SNAP. This
When neural impulses arrive at the active electrode, the in OMet Peak Amplitude
strument displays the associated electrical activity and the ini L8tency Latency (JLV)
tial portion of the SNAP becomes manifest. If we assume that (ma) (ma)
the SNAP action potential propagates at about 50 meters/second
(mls), the travelling wavefront of this action potential achieves a
distance of 4 cm from the active electrode by the time the SNAP
peak reaches the active electrode. This distance is determined
by using the formula, nerve conduction velocity (NCV) equals
distance (D) divided by time (t):
'1(
B~
2.8
2.8
3.5
3.3
27
20
NCV =D .;- t; 50 mls =D .;- 0.8 ms, or D = 4 cm
In other words, the SNAP rise time has a physical/electrical
expanse along the nerve that approximates 4 cm. As a result, if
the reference electrode is placed at 4 cm or closer to the active
electrode, it records some portion of the SNAP's rising (nega
cJl-J 20IlV
2.8 3.5 29
tive) phase during the same time that the active electrode is also 2ms
recording a time-delayed but nevertheless rising phase. Because
the instrument uses differential amplification, similar data (in Figure , 5-2. Antidromic vs. orthodromic SNAPs. A, An an
this case, the SNAP's leading aspect) recorded from the active tidromic median nerve SNAP is recorded with an active/reference in
and reference electrodes result in cancellation of some informa terelectrode separation of .. cm. B, Orthodromic activation of the
tionP This cancellation is the so-called elimination of common median nerve over the same distance using an active/reference inter
mode signals. An interelectrode separation of less than 4 cm, electrode separation of 2.5 cm. Note the smaller amplitude and
therefore, leads to the cancellation of data contained in the shorter peak latency for the orthodromic compared with the an
SNAP and prevents the SNAP peak from maximizing because tidromic SNAP. C, Increasing the active/reference interelectrode sepa
the potential is terminated prematurely (Fig. 15-1). If data are ration of the recording electrodes in B results in similar peak latencies
eliminated as a common mode signal, the SNAP amplitude is re for both antidromic and orthodromic techniques as well as ampli
duced. Similarly, if the SNAP peak is terminated prematurely, an tudes. In this patient there is little subcutaneous tissue between the
earlier than normal peak latency is produced. The SNAP's onset recording electrodes and underlying nerve, minimizing an initial posi
latency is unaffected by an interelectrode separation of less than tive deflection for the orthodromic studies.
4 cm because the active electrode always detects the action po
tential's negative sink arrival before this aspect of the action po
Antidromic VS. Orthodromic Studies
tential reaches the more distally placed reference electrode. In
other words, the distance between the cathode (site of nerve acti A number of issues concerning orthodromic and antidromic
vation) and the active recording electrode is not altered. SNAP NCS pitfalls are relevant to electrode location. An appar
Both nerve conduction velocity and rise time directly influ ent discrepancy between antidromic and orthodromic peak
ence the "optimal" distance between active and reference elec SNAP conduction velocities is exemplified by several studies
trodes. If the maximal conduction velocity of the SNAP is 60 showing that the median nerve's antidromic SNAP peak latency
mls and the rise time remains at roughly 0.8 ms, an interelec is longer than the orthodromic SNAP peak latency over the
trode separation of 4.8 cm is necessary to maximize the SNAP's same distance. 12•64,18 Multiple theories were advanced to account
amplitude and peak latency. Because the SNAP's onset is trav for this discrepancy, but the solution is found in interelectrode
eling faster, it proceeds comparatively further along the nerve recording distance. Antidromic studies typically use digital ring
trunk, necessitating a relatively greater interelectrode separa electrodes with a separation of 4 em, whereas orthodromic stud
tion. However, a patient with a peripheral neuropathy who has a ies record the median nerve's SNAP over the wrist with a bar
maximal conduction velocity of 35 mls requires an interelec electrode using an electrode separation of roughly 2.5 cm. Use
trode separation of only 2.8 cm, assuming a SNAP rise time of of equal electrode separations for both antidromic and ortho
0.8 ms. If an increase in SNAP duration and rise time occurs dromic techniques results in SNAPs with similar peak latencies
(e.g., 1.2 ms; decreased temperature, nerve pathology), a corre (Fig. 15-2).8.13
sponding increase in electrode separation is required to resolve Antidromic SNAPs occasionally may be contaminated by
fully the SNAP amplitude and peak latency (e.g., 50 mls = D.; volume-conducted motor responses from coincidentally acti
1.2 ms = 6.0 cm of interelectrode separation). vated hand intrinsic muscles. This problem can occur with either
The effects of peak latency and amplitude have important median or ulnar nerve studies. [n most cases, it is resolved by
clinical implications. If only the onset latency or nerve conduc moving the active electrode slightly more distal on the digit or
tion velocities are measured, electrode separation is of little having the patient actively spread the fingers. Rarely, the
concern. Amplitude, however, can be significantly affected. The volume-conducted motor artifact continues to obscure the SNAP,
closer the two electrodes, the more dramatic the amplitude re in which case an orthodromic study should be performed.
duction (see Fig. 15-1). The reduced amplitude arising from Orthodromic SNAP amplitudes occasionally can be rather
electrodes that are spaced too closely, with a normal onset la small and hence somewhat hard to record. This situation results
tency may lead to the erroneous conclusion that axonal loss is from the distance between the active electrode and underlying
present. Shortened peak latency due to reduced interelectrode nerve. The amplitude of a potential declines precipitously as the
separation also may convert a borderline abnorrnallatency into active electrode is displaced from the electrical generator.
a normal latency. The wide variation in normal SNAP ampli Antidromic SNAPs can be larger than orthodromic responses be
tudes combined with an artifactually shortened latency may cause there is usually less subcutaneous tissue between the active
lead to a false-negative result. electrode and nerve in the digital regions. Orthodromic SNAPs
544 - PART III PATIENT CARE-RELATED ISSUES
c1r
the tendon of the investigated muscle to minimize volume con
duction effects from other excitable tissue (volume-conducted
muscle and far-field potentials), which can alter CMAP amplitude
3.5 6600 5.2
B~~
ings. A, Routine CMAP recording from the thenar eminence after
median nerve wrist excitation is performed with the active electrode
on the abductor pollicis brevis' motor point and a reference electrode
positioned distal on the thumb.The CMAP has an initial negative onset
C~""'I
electrodes J~v
2. Use only a small amount of electrolyte cream beneath all electrodes 1.Oms
3. Place ground electrode next to active recording electrode be
Figure 15-8. Effect of anodal rotation. An antidromic median
tween it and the cathode
SNAP is recorded with the cathode (Ca) located 7 cm from the active
4. Only use current strength and duration sufficient to achieve a recording electrode (Ac) with the reference electrode (R) located 4
supramaximal response cm distal to the active electrode. The anode (An,) is 2.5 cm proximal
5. Reduce the impedance between the skin and all electrodes to the cathode. Trace A reveals the SNAP with an ill-defined onset la
6. Elevate the low-frequency filter tency because it is clearly affected by the stimulus artifact. Rotating the
anode about the cathode in O.5-cm increments (An2-An~) eventually
7. Rotate the anode about the cathode
results in suppression of that portion of the stimulus artifact interfer
8. Use a needle cathode/(anode) ing with the SNAP's onset permitting measurement of this parameter
* Use sparingly, if at all because of tendency to distort the waveform. (Traces 8-D).
Chapter 15 ELECTRODIAGNOSTIC MEDICINE PITFALLS - 547
A~~T.r.~r----========-----------~
------------------------
desired location to excite the nerve optimally while the anode is with lesser current levels for either nerve or muscle responses. It
repositioned in small increments about the cathode, taking care may be possible, particularly in diseased nerves with elevated
not to rotate the anode so that it is between the cathode and depolarization thresholds, to reduce a borderline abnormal re
active electrode. This maneuver is successful because it at sponse latency into the normal range, producing a false-nega
tempts to align the isopotential voltages generated by the stimu tive result.
lator at the recording electrodes (Fig. 15-9). When similar
voltages arising from the stimulator align at the active and refer
ence electrodes, they are reduced or eliminated as a common Peek Latency (ma,
mode signal through differential amplification. If all of the Superficial
A~
Radial lIed.n
above maneuvers fail to eliminate the stimulus artifact, the only
remaining option may be to increase the distance between the
cathode and active electrode to increase the separation between 3.7
AJ~Vlan
the desired response and the stimulus artifact. Previously used
reference data may no longer be valid.
Peak Latency (ms) result in neural excitation at a site other than that aligned with
SUperficial
the cathode (Fig. 15-10). The variability induced by attempting
Median shortcuts of stimulating two nerves simultaneously also can
Radial
lead to false-positive results if the site of neural activation for
2.4 the radial nerve is closer to the active recording electrode while
that for median nerve excitation is further from the active
recording electrode compared with individual neural excitation
at the designated stimulus locations (Fig. 15-11). In short, it is
B 2.6 best not to attempt to activate more than a single nerve at a time
to ensure accurate data collection. Selective median and radial
nerve activation is a sensitive technique for diagnosing carpal
eve: J10l V
2.3 2.8
tunnel syndrome, but simultaneous median/radial nerve stimu
lation through volume conduction is a questionable short cut
prone to many pitfalls and should be avoided.
Stimuli delivered over multiple short interstimulus distances
across a presumed neural injury site define the so-called "inch
ing" or, in reality, "centimetering" technique. A nerve is acti
vated sequentially at 1-cm intervals, usually across the carpal or
cubital tunnel region, in an attempt to define a focal amplitude,
2ms
duration, or latency change that indicates in a more precise
Figure 15-11. Median/radial nerve stimulation.A,A recording manner (within 1-2 cm) the presumed site of neural compro
of the superficial radial nerve is performed along the radius 10 cm mise. The anatomic relationship between the median or ulnar
proximal to an active recording ring electrode located on the first nerve and its surrounding connective/muscular tissues is the
digit. A SNAP with a peak latency of 2.4 ms results. B, The median basis for a possible pitfall, predisposing the "inching" technique
nerve is also stimulated 10 cm, as measured along the course of the to false-positive studies. Specifically, there is a transition zone
median nerve, proximal to the active electrode. The generated SNAP for the median nerve as it passes beneath the proximal extent of
has a peak latency of 2.6 ms. The median/radial interpeak latency is the carpal tunnel and for the ulnar nerve between the two heads
normal at 0.2 ms. C,Activating both nerves simultaneously by produc of the flexor carpi ulnaris muscle under the intermuscular con
ing a volume-conducted response midway between both nerves at the nective tissue bridge (arcuate ligament). The amount of current
wrist produces a shortening of the superficial radial response but a required to activate the nerve supramaximaUy with a surface
lengthening of the median response creating an interpeak latency of stimulator increases significantly, predisposing to activation of
0.5 ms, which is suspicious for carpal tunnel syndrome. Performing this the nerve closer to the recording electrode and thereby produc
technique alone may lead to the conclusion that pathology is present. ing a marked interpotential latency change proximally com
pared with just distally to the connective tissue transition. This
"abnormal" latency shift arising from a volume-conducted stim
In addition, attempting to stimulate two or more nerves si ulus can mimic a latency shift secondary to neural pathology
multaneously through a volume-conducted stimulus-between thereby creating a false-positive study or possibly accentuating
the median and radial nerves at the wrist, for example-may a mild abnormality. The onset latency appears to be less variable
~
2 1 not be used. At some locations for both onset
0.1 0.2 and peak latency measurements a zero differ
4 2 0.2 0.1 ence is noted despite careful cathode placement
3 0.0 0.2 and I-cm separation, implying a volume-con
4 0.1 0.0
S ducted activation of the nerve.
Chapter 15 ElECTRODIAGNOSTIC MEDICINE PITFALLS - 549
c~-
clearly recognizable response with a normal latency and ampli
tude (Fig. 15-14). This suggests minimal, if any, pathology af
fecting the ulnar nerve. Interestingly. stimulating the second
interspace (presumably the median nerve) with the active elec
trode in the same location (over the ulnar nerve) results in a
well-defined potential of similar latency and amplitude. Stimu
lating the fourth palmar interspace but recording over the D
median nerve at the wrist also generates a large potential with
essentially the same latency as the two previous responses.
Finally. stimulating the second palmar interspace while record
ing over the median nerve at the wrist 8 cm proximal produces a
large potential with equivalent latencies to all of the previously Figure , 5-16. Facial nerve activation. A. Stimulation of the left
defined waveforms. If only the routine mixed-nerve techniques facial nerve not uncommonly results in a CMAP with an initial positive
for median and ulnar nerves are used without altering the deflection because of a diffusely localized motor point (recording from
recording and stimulating sites, a normal response for each the orbicularis oculi). In some but not all persons, relocating the active
nerve is suggested despite the obvious loss ofaxons. electrode can result in an initial negative deflettion. B, Left facial nerve
Confusion also may arise when a complete median nerve activation over the parotid gland region results in a well-defined
lesion is present at the wrist. Stimulating the median nerve at CMAP as recorded from the left nasalis muscle (reference electrode
the wrist with high-current intensities while recording from the positioned on the right nasalis muscle). C, Direct activation of the
thenar muscles can result in a relatively small-amplitude CMAP masseter muscle (cathode distal along the mandible) reveals a well-de
with an initial positive deflection (Fig. 15-15). Relocating the fined CMAP as recorded from the active electrode positioned over
active electrode usually fails to generate a CMAP with an initial the nasalis muscle, resulting in a volume-conducted, negative onset
negative deflection. It is then possible to conclude that there is CMAP from the masseter muscle. D, Stimulation posterior to the neck
sparing of some median nerve fibers, but a difficult-to-Iocate of the mandibie away from the masseter muscle results in a large
motor point when the initial positive deflection is present. nasalis muscle CMAP With a slightly different morphology compared
Stimulating the median nerve at the antecubital fossa, however, with the CMAP obtained with facial nerve activation over the parotid
fails to generate a CMAP. This can lead to the erroneous con gland anterior to the ear. The different morphologies of the two
clusion that a conduction block, in addition to a possible axon CMAPs is likely a result of some volume-conducted CMAP interfer
loss lesion (small-amplitude CMAP), in the forearm affects the ence from the masseter muscle (cathode anterior to the ear and
median nerve. However, activating the ulnar nerve at the wrist hence over the masseter muscle).
Chapter 15 ElECTRODIAGNOSTIC MEDICINE PITFALLS - 551
the recording electrodes are in the proximity of a group of mus fact that it is relatively easy to activate the masseter muscle di
cles innervated by more than one nerve. rectlyas it lies beneath the parotid gland and hence cathode (see
Fig. 15-16). The masseter muscle's CMAP can be volume-con
Direct Muscle Activation ducted to any electrode location on the face and even have an
Facial nerve studies can lead to a number of potential pitfalls. initially negative deflection in some patients. Even if the mas
It is not uncommon for some facial muscles to have poorly de seter CMAP has an initial positive deflection, it can be easily
fined motor points, especially the orbicularis oculi and oris mistaken for a facial nerve response because many persons have
muscles. As a result, facial nerve activation can produce wave facial CMAPs with initial positive deflections (see above).
forms with an initial positive deflection or bifid morphology Masseter muscle activation can be verified by palpating the
(Fig. 15-16A). Relocating the active electrode may help to muscle during stimulation or locating a needle electrode within
define a CMAP response more clearly in some patients, but not the muscle and recording a CMAP. This potential pitfall can be
in all. The difficulty arises when the left and right CMAPs have avoided in some patients by locating the cathode's stimulator
different morphologies, thereby rendering side-to-side ampli either well posterior to the neck of the mandible in an attempt to
tude comparisons for prognostic purposes of limited value. If activate the facial nerve as it exits the stylomastoid foramen
this situation arises, it is best to choose a muscle other than the (firm pressure is required) or inferior to the zygoma, thereby
orbicularis oris or oculi, such as the nasalis muscle, which has a stimulating only a few neural branches while recording from the
relatively well-defined motor point. nasalis muscle. The anode in both situations should be posi
It is certainly possible for the cathode (anode with high CUf tioned away from the masseter muscle to avoid anodal muscle
rent intensities) to activate a skeletal muscle directly when activation. Moreover, a current intensity not too much larger
placed on or in the proximity of the muscle's motor point. The than the normal side should be used to avoid a volume-con
generated CMAP can be recorded even by a distant active elec ducted depolarizing current either from the cathode or anode,
trode through volume conduction. This possibility is particu which may activate the masseter muscle. Long pulse durations
larly problematic during the investigation of patients with a and high current intensities may be required for optimal activa
facial nerve lesion. For example, in patients with Bell palsy and tion of diseased nerves, but this can lead to a possibly false-neg
progressive loss ofaxons, stimulating the facial nerve at the ative study (falsely interpreting a masseter CMAP as arising
mandible's neck region through the substance of the parotid from a facial nerve-innervated muscle), suggesting a good prog
gland on a daily or every-other-day basis allows comparison of nosis despite complete wallerian degeneration of the facial
the affected and unaffected facial muscle CMAPs to determine nerve. An absent blink reflex and no voluntary motor units on
the disease progression and degree of axonal loss. It is not un needle electromyography are not of much help because they
common for the affected CMAP first to decrease in amplitude cannot distinguish between complete axonal loss and conduc
and then to level off after several days while the patient contin tion block with some axonal loss because of the lesion's proxi
ues to display a reduction in facial muscle function. Cessation mal location. Unfortunately, in some patients the masseter
of CMAP amplitude reduction on the affected side in combina muscle is easily excited and hence results in a volume-con
tion with continued functional decline can lead to the conclu ducted CMAP that continues to interfere with the accurate doc
sion that a conduction block is present and axonal loss has umentation of a facial nerve response. In some patients,
ceased. This conclusion may be valid or completely erroneous masseter muscle activation may simply render the electrophysi
and lead to an unwarranted good prognosis. The error lies in the ologic data of limited prognostic value, although stimulating
t
Recording Stimulator
A Electrodes
B
R Ac A C
C
--0-0
Bipolar Anodal Stimutation • • S l
flV---
D ~
R Ac C A
E --0-0
Figure 15-17. Anodal stimulation.Waveforms generated by activating the superficial radial nerve with the stimulating and recording mon
tages depicted in diagrammatic fashion adjacent to the recorded potentials (C: cathode; A: anode;Ac: active recording electrode; R: reference
recording electrode). A-D, Bipolar anodal stimulating montage produces two peaks (S {short} and L {long}) as the current intensity is progres
sively increased from 20 rnA (A), 25 rnA (B). 30 rnA (C), up to 35 rnA (0). Peak L emerges first; then, with increasing current, peak S arises and in
creases in amplitude, whereas the magnitude of peak l declines. E, Sensory nerve action potential obtained with standard bipolar cathodal
stimulating technique. (From Dreyer SJ. Dumitru DD, King JC:Anodal block versus anodal stimulation: Fact or fiction. Am J Phys Med Rehabil
1993;72: 10-18, with permission.)
SS2 - PART III PATIENT CARE·RELATED ISSUES
posterior to the mandibular neck (the facial nerve as it exits the response with a shorter latency than the cathode response,
stylomastoid foramen) should help avoid masseter muscle acti which increases in amplitude with sequential current elevations.
vation in a number of patients. A simultaneous reduction in the potential is produced by the
cathode. In short, the cathode produces a response at moderate
ANODAL BLOCK/STIMULATION VS. current levels, whereas the anode can generate a potential at
CATHODE/ANODE REVERSAL higher current intensities. The action potentials from the anpde
also propagate toward the cathode and produce a partial colli
Whenever a nerve is stimulated, it is mandatory to ensure that sion blockade of cathodal action potentials. Placing the cathode
the cathode is properly positioned not only over the appropriate closest to the active electrode prevents detection of anodal
nerve but also with respect to the anode. It is easy to reverse the action potentials because of cathodal blockade (depolarization)
position of the anode and cathode inadvertently so that the and the collision between neural action potentials induced by
anode rather than the cathode is closest to the active recording the cathode and anode. Therefore, using an initial high current
electrode. Two concerns are frequently discussed when this sit intensity and long pulse duration with the anode interposed be
uation occurs: (I) anodal block and (2) latency delay. tween the active electrode and cathode may produce a bifid
SNAP response, leading to confusion (see Fig. 15-17). If the
Anodal Block shorter latency is chosen, a false-negative response can be pro
Anodal block is theorized to occur when the anode is posi duced because it arises from the anode, not the cathode.
tioned between the cathode and active electrode. Anodal current The blink reflex can result in a particularly interesting and
theoretically hyperpolarizes the neural tissue in its immediate definitely confusing set of waveforms because of an attempt to
vicinity, preventing action potential propagation past the anode minimize stimulus artifact. The rather close proximity of the
site. Stimulating the nerve with the anode closest to the active recording and stimulating electrodes creates a situation in which
electrode should result in a small or absent potential because of stimulus artifact can significantly interfere with documentation
the hyperpolarizing blockade of neural conduction. Anodal and measurement of the Rl response. In recording any facial
block has been demonstrated in animal preparations with spe nerve response, facial oils and make-up must be removed thor
cial ramp currents and direct stimulation of the exposed nerve oughly to minimize the stimulus artifact across the skin surface,
with high-intensity anodal currents. In humans, however, anodal which adversely affects waveform recognition. If a large stimu
block does not occur during routine nerve conduction studies lus artifact remains, the anode can be rotated about the cathode
using current intensities delivered by instruments and tolerated location at the supraorbital notch to reduce effectively any inter
by patients. 22 On the contrary, the anode can depolarize neural ference with the R 1 response. This procedure can generate a
tissue through an imperfectly understood mechanism. Inter blink reflex response (as recorded with two channels), revealing
posing the anode between the cathode and active electrode can an RI waveform on both channels (Fig. 15-18). The documenta
result in the production of two responses (Fig. 15-17). At mod tion of a bilateral Rl can certainly cause confusion and call into
erate current intensities, the expected cathode response is ob question the most appropriate diagnosis. The production of a bi
served. Increasing the current to maximal tolerance generates a lateral Rl response is not the result of a latent anomalous path
way but a pitfall of electrophysiologic testing. When the anode is
rotated about the cathode toward the midline and opposite side,
the anode may act to depolarize (anodal stimulation) the con
tralateral supraorbital nerve, thereby effectively producing a bi
left lateral stimulation and hence bilateral simultaneous Rl and R2.
The combination of stimulus artifact suppression through
anode rotation and anode stimulation results in the generation
right of an artifactual contralateral RI, possibly leading to a false
negative result. Specifically, if an Rl is pathologically absent on
an affected side (e.g., afferent/efferent principal sensory nucleus
brainstem pathway lesion) but the anode is rotated toward the
normal contralateral side and inadvertently activates the normal
supraorbital/seventh nerve pathway, a normal contralateral Rl
and possibly bilateral R2 can be generated with normal laten
right cies from the affected side. The Rl occurs on the side opposite
to that stimulated but may be misinterpreted as normal during
J~v
the examination or recognized as nonphysiologic later, with the
discrepancy falsely attributed to mislabeling the traces. The
1Oms end-result is a normal blink reflex study because the unaffected
supraorbital nerve is activated twice: once by the cathode over
Figure 15·18. Blink reflex. left supraorbital nerve stimulation gen the normal nerve and again by the anode rotated toward the un
erates the typical blink reflex response with an ipsilateral RI and R2 affected side. It is thus important during the performance of the
(A,). and a contralateral R2 (A~. Rotating the anode toward the right blink reflex to avoid locating the anode close to or past the mid
side while maintaining the cathode positioned over the left supraor line because the contralateral supraorbital nerve can be acti
bital nerve can result in continued cathodal excitation of the left vated by the anode, possibly leading to a false-negative study.
supraorbital nerve and anodal activation of the right supraorbital
nerve fibers. The end-result is stimulation of both right and left supra Cathode/Anode Reversal
orbital nerves with bilateral Ris and superimposed R2s (B, and 8 2) When the cathode and anode are reversed, an alteration in the
originating from both supraorbital nerves. anticipated response latency occurs, not because of anodal
Chapter 15 ELECTRODIAGNOSTIC MEDICINE PITFALLS - 553
blockade but simply because the cathode is further displaced point. In either case, a false-positive study is observed or a
from the active electrode. 23 The effects of cathode/anode rever positive result may be inappropriately accentuated.
sal apply equally to motor and sensory NCS. This effect can be
readily demonstrated by a simple example using routinely AMPLIFICATION
supramaximal current intensities. Suppose that the median
nerve is activated at the wrist 8 cm proximal to the thenar emi The amplifier is one of the basic electronic components of the
nence and again at the antecubital fossa 23 cm proximal to the instrument. Its main function is to magnify small biologic sig
wrist site. 23 The observed distal and proximal motor latencies nals so that they can be observed and analyzed. One of the pri
are 3.1 ms and 7.1 ms, respectively, with a nerve conduction ve mary parameters assessed in routine NCS is waveform onset
locity of 58 mls. A separation of 2.5 cm is present between the latency. At comparatively higher magnifications, increasingly
cathode and anode. It takes 0.4 ms for the action potential tra smaller deviations from the baseline are detected, thus tending
versing the median nerve to pass between the cathode and anode to shorten any potential's onset. As a result, the same potential
(58 mls =2.5 cmlt; t =0.4 ms). recorded at sequentially higher amplifier sensitivities reveals a
If the median nerve at the wrist is inadvertently excited with progressive shortening of onset latency (see Fig. 15-6). The
the anode at the 8-cm site as opposed to the cathode and a documentation of progressively shorter-onset latencies is of pri
supramaximal current is used, the effective site of neural acti mary concern during the investigation of CMAP distal and
vation occurs 2.5 cm more proximal than expected at 10.5 cm proximal motor latencies. If more than one stimulus site is used
from the active recording electrode. It is assumed, however, for any given nerve, all comparative latencies must be deter
that the practitioner is unaware of this cathodal mislocation. mined at the same amplifier sensitivity. A failure to do so can
The observed distal motor latency is 3.5 ms (3.1 ms + 0.4 lead to erroneous determinations of nerve conduction velocity.
ms).23 Correctly performing the antecubital stimulation (cath The concept of noncomparative latency values at different am
ode distal) results in a proximal motor latency of 7.1 ms, but plifier sensitivities is a basic aspect of instrumentation and espe
the calculated time difference is 3.6 ms (7.1 ms - 3.5 ms) in cially important to comprehend because it directly influences
stead of 4.0 ms, resulting in a conduction velocity of 64 m/s. reference data. When a particular NCS technique is used, all of
An increase of 6 m/s above that actually present is obtained. the instrumentation parameters used to arrive at the data must
Reversing the proximal cathode/anode location inadvertently be duplicated. For example, an amplifier setting of 500 )lV/div
results in a documented prolongation of the proximal motor la for determining onset latencies of the median nerve must be
tency to 7.5 ms. If the wrist stimulation is performed correctly, used by all practitioners using this reference data. Sensory stud
a conduction velocity of 6 mls less than physiologically present ies are also subject to the requirement of instrumentation para
(52 m/s) results. An inadvertent reversal of both proximal and meter duplication with an alteration particularly in onset latency
distal cathode/anode locations produces the physiologically determination with different amplifier sensitivities (Fig. 15-19).
correct conduction velocity (58 mls) as the additional 0.4 ms is Sensory nerve action potentials may be absent in patients with
subtracted. However, the absolute distal and proximal latencies peripheral nerve disease. Before concluding that a response is
continue to be prolonged. If the above example is carefully per absent, however, it is necessary to increase the amplifier's sensi
formed, mathematically predicted and experimentally observed tivity. The amplifier settings established by the factory for sen
latencies and velocities agree without invoking the concept of sory studies are frequently sufficient to demonstrate a normal
anodal block. 23 As can be seen, it is possible to produce con SNAP (10-50 IlV/div) but insufficiently sensitive to reveal small
duction velocities and latencies that may predispose to the erro amplitude SNAPs. The low amplifier settings generate a quiet
neous conclusion that disease is present (artifactually lowering baseline, which produces a "pretty" response but frequently re
conduction velocity or increasing the distal motor latency) or sults in the conclusion of an absent potential. Increasing the
absent (artifactually elevating nerve conduction velocity).
CATHODE/ANODE STABILITY
The stability of the cathode and anode is equally as impor AmplIfIer an.t Peek
tant as properly securing the active and reference recording ",VIcIn) LMency a..tency
(1M) (1M)
electrodes (see above). If the cathode is serially displaced fur
ther from the nerve during attempts to define a supramaximal
stimulus, a less than supramaximal CMAP amplitude is pro A 10 2.8 3.6
duced. This is a common occurrence because the practitioner
is frequently concentrating on the intended potential's wave
form as displayed by the instrument while applying pressure
J
1ms
to the stimulator. The combination of lateral pressure and elec B 20 2.9 3.6
trolyte cream predisposes the cathode to slip away from the
nerve. It is important to monitor cathode and anode location
constantly at the beginning, during, and at the completion of a
C~ 50 2.9 3.6
stimulation series. This potential pitfall is particularly critical D~ 100 3.0 3.6
during repetitive nerve stimulation studies (see Fig. 15-7).
Failure to secure the recording and stimulating electrodes Figure 15-19. Amplifier effects on latency. Recording an an
properly can result in a sequential reduction in the CMAP, tidromic median SNAP at different amplifier sensitivities reveals that a
possibly simulating a pathologic decrement. Either the stimu sequential reduction in amplifier sensitivity results in a progressive
lating electrodes moves off the nerve trunk, or the recording delay of the potential's onset latency (A-D). The peak latency, how
electrodes are sequentially displaced from the muscle's motor ever, is not appreciably affected by these amplifier sensitivities.
554 - PART III PATIENT CARE-RELATED ISSUES
A FILTERS
All commonly used electrodiagnostic instruments consist of
variable low- and high-frequency filters. A low-frequency filter
is also known as a high-pass filter because it permits high fre
quencies to pass unaltered but limits the recording of low fre
B quencies. Similarly, a high-frequency filter (low-pass filter)
allows low frequencies to pass unaltered but limits the amplifica
tion of high frequencies. The combination of low- and high-fre
quency filters limits the amplification of excluded frequencies
c and creates a window or bandpass of frequencies capable of
being observed. The rationale for variable filter settings is to in
clude the majority of frequencies comprising the biologic signal
of interest and to eliminate those not contained in the signal,
which are considered to be noise.
o All biologic signals can be conceptualized as composed of
variable amounts of high and low frequencies of various ampli
1r_~l
..
niques are used can a response truly be considered absent.
F...,....cy
Low
.......ncy
FllllrCHz)
Oneet
l..aItIncy
eml)
....
a...ncy
(!III)
(PY)
remain in the observed waveform. If data are removed from the
.......
..............
DunIIIan
(mI)
.1=
A 10,000 2.9 3.4 28.0 1.3 figure 15-21. Low frequency filter effect
on SNAP. Recording an antidromic median nerve
SNAP with different low-frequency filters reveals
a number of interesting waveform alterations
10,000 10 2.9 3.4 28.5 1.2
(A-D). As the low-frequency filter is elevated
from I Hz to 300 Hz, the SNAP's onset latency is
J-v
Chapter 15 ELECTRODIAGNOSTIC MEDICINE PITFALLS - 555
SNAP, less information is available to contribute to the SNAP; peak latency shortens. An extraterminal phase also arises. Onset
hence its amplitude should decline. If increasingly more low latency does not change because it is a quickly changing portion
frequencies are removed, the resulting SNAP also should con of the SNAP (contains significant high-frequency subcompo
tain comparatively more high frequencies. This suggests that nents) and is thus not affected by altering the low-frequency
the waveform should be preferentially influenced by higher fre filter. As a result, an inappropriately elevated low-frequency
quencies and occur faster or earlier in time (shorter latency) filter dramatically reduces the SNAP's amplitude while shorten
compared with the waveform with more low frequencies. The ing its peak latency. This can give the false impression of re
duration of spikes also should decrease because the remaining duced axonal content in the nerve under investigation, with a
waveform has preferentially higher frequencies. A signal with normal peak latency possibly leading to the conclusion that an
higher frequencies also should appear more like an alternating axonal process is present. If this same instrumentation error is
current signal (more phases) than a direct current signal (no replicated for all nerves examined, a widespread axonal periph
phases). Hence, the potential may increase in number of phases eral neuropathy can be erroneously diagnosed. In addition, an
compared with a potential with more low frequencies. Finally, abnormal peak latency can possibly be shortened into the
subtracting low-frequency information should truncate or normal range. Similarly, excessive temporal dispersion may be
shorten the potential's total duration (Le., a shorter onset to minimized. Thus, false-positive and false-negative results can
baseline return). be obtained, resulting in significant confusion.
Actually recording a SNAP with serial increases in the low The CMAP is even more profoundly affected than the SNAP
frequency filter demonstrates all of the above hypothesized by elevating the low-frequency filter (Fig. 15-22). All of the
findings (see Fig. 15-21). The total potential duration shortens, above SNAP alterations are replicated for CMAPs but to a greater
as does the negative spike duration. A dramatic decrease in degree. The exaggerated CMAP response is probably related to
base-to-peak and peak-to-peak amplitude is noted while the the longer duration of the CMAP (Le., relatively more pronounced
~-
LatInCy
(1lY)
FIIIr(Hz) FIIIr(HzI (mal (mal (mal
Ejjr2ma
500 3.0 3.8 21 1.5
556 - PART III PATIENT CARE-RELATED ISSUES
low-frequency components). If the CMAP is dominated by low of data results in a variable waveform amplitude reduction. The
frequencies, any alteration in the CMAP's low-frequency sub entire waveform is delayed in time, especially the onset and
components results in significant waveform distortions. peak latencies. An increase in the negative spike duration also
occurs. Because the instrument's internal noise consists primar
High-Frequency Filters ily of high frequencies, the overall appearance of the waveform
High frequencies are defined as those exceeding 500 Hz. The is more "smooth."
effects of extracting high frequencies from a waveform can be All of these effects can be observed to variable degrees when
described in a manner similar to that used for low frequencies. either a SNAP or CMAP is recorded with a low-frequency filter
A signal from which high frequencies are removed is preferen of 1 Hz with sequential lowering of the high-frequency filter
tially influenced by the remaining low frequencies. The charac from 10,000 Hz to 500 Hz (Figs. 15-23 and 15-24). The SNAP
teristic of low frequencies is that they take longer to occur. The demonstrates the above waveform alteration more readily than
effects on biologic signals are opposite effects to those de the CMAP because it contains more higher frequencies, as
scribed for elevating the low-frequency filter. Specifically, loss demonstrated by a faster rise time and shorter negative spike du
ration. The major clinical effects are a delay in onset and peak
latencies with some degree of amplitude reduction. It is possible
to prolong both of these parameters to induce a false-positive
result simulating a distal peripheral neuropathy. Of note, the
conduction velocity is not affected because both distal and prox
A Wrist 8,000 4.4 imal latencies are equally delayed and amplitude is affected
only mildly, supporting the erroneous conclusion of a possible
.-t
distal neurogenic process .
C-AV
straightforward and consists of exciting a nerve at two loca
tions, measuring the interstimulus distance, and dividing this
distance by the time difference of neural conduction between
Axilla 7.125 5.0 stimulus sites. A number of issues regarding both motor and
sensory nerve conduction determinations require discussion.
A Be
J5OOC4tV Potential NCS pitfhlls include amplitude variability with stimu
5ms lus site location and one versus two neural activation points for
velocity calculations.
Amplitude Variability
There is a physiologic decline in both SNAP and CMAP am
plitude as the site of neural activation increases with respect to
Figure 15-25. Distance effect on CHAP. Only a mild drop in am the active electrode location. The CMAP baseline-to-peak am
plitude and mild increase in negative spike duration is noted for plitude reduction should not exceed about 20-25% (tibial nerve:
CHAPs activated at common locations such as the wrist (A). elbow 41 %) of the CMAP obtained at the site closest to the active
region (B), and proximal arm or axilla (C). recording electrode for most interstimulus distances not exceeding
Chapter 15 ELECTRODIAGNOSTIC MEDICINE PITFALLS - 557
roughly 20 cm (Fig. 15-25).67 A side-to-side CMAP amplitude S1lmu1ua Amplitude . . . . " . SpIke
difference for the same nerve and comparable stimulus sites Location (JIY) Duration emsl
52 mls. These velocities remain considerably below those of the Specifically, if the interstimulus distance is decreased to 10
forearm motor studies, and the improvement is comparably less cm with the nerve maintaining the same 50 mls conduction ve
than for sensory studies with equivalent correction factors. The locity, an interstimulus time of 2.0 ms is presumed. Using the
remaining discrepancy between the double and single stimulus two standard deviation measurement errors, an overall calcu
site motor studies may result from more distal motor nerve fiber lated conduction velocity error may be as much as 20%:
tapering in the terminal intramuscular arborization, larger neu
romuscular junction delays, latencies of activation longer than Example C: NCV = (10 cm - 0.47 cm)-=
0.1 ms, or other ill-defined factors. Clearly a single stimulus site (2.0 ms + 0.26 ms) = 42 mls
for determining motor conduction velocities is inappropriate. A
parameter known as the residual latency can be calculated, Example D: NCV =(to cm + 0.47 cm) -=
which is the difference in latency between the value predicted (2.0 ms 0.26 ms) =60 mls
on the basis of a forearm velocity propagating along the distal 8
cm and the actual time measured. 50•55 In the above example the In these examples, a patient with presumed conduction veloc
residual latency is 2 ms: distal motor latency - predicted time ity of 50 mls can have a decrease or increase of roughly 10 mls
(NCV -=- distal distance) =3.3 - (6 mls -=- 8 cm) =2.0 ms. A sim (20%) by decreasing the distance from 20 cm to 10 cm. The
ilar calculation can be performed to arrive at sensory residual chance of generating a false-positive or false-negative study in
latencies. The diagnostic utility of residual latency determina creases as the error essentially doubles.
tion remains to be validated in large patient series. Such errors should be considered in comparing patient data
with reference values. Sweep speeds of 1-2 ms/div can reduce
Short Interstimulus Distances the relative latency error, but not the distance error, which re
The validity of calculated nerve conduction velocities de mains proportional to the ability to measure length accurately
pends directly on the accuracy of CMAP latency and interstim with a tape measure. Because of this limitation, relatively large
ulus distance measurements. The distal and proximal latencies rather than small interstimulus distances should be used to min
should be obtained at identical sweep speeds. An inherent vari imize NCV calculation errors. According to convention, con
ability and limit to accurate time and distance measurements duction velocities should be determined for distances greater
exist. The relevance of these limitations can be illustrated by than 10 cm. The to-cm distance is not magical, however, and
having 10 electrodiagnostic medicine practitioners measure a the larger the distance, the less the effect of small distance
set distance on a patient's forearm and determine the median errors. As large a distance as possible should be used to arrive at
nerve CMAP's onset latency at a sweep speed of 5 ms/div. The the appropriate answer to the clinical question. When "inching"
standard deviation for these latency measurements is 0.13 ms techniques are used, latency values rather than conduction ve
with the instrument's minimum cursor resolution of 0.21 ms. A locities should be used to reduce the overall error by eliminating
1-mm resolution metallic tape measure is used to determine the error introduced by measurement.
interstimulus wrist/forearm distance on a single volunteer. The
mean and standard deviation distances measured for the 10 PHYSIOLOGIC FACTORS
practitioners are 23.05 cm and 0.235 cm, respectively. If two of
the above standard deviations are used (includes 80% of mea Temperature, age, anomalous innervation, and central modu
surements), the effect of using relatively "short" interstimulus lation can influence NCS. Patient limb length (height) and
distances can be illustrated. gender may have some effect on NCS, but the degree of alter
Given an interstimulus latency difference of 4.0 ms and dis ation with these two parameters is debatable. It is important to
tance of 20 cm ± 2 standard deviations (2 standard deviations in be aware of possible NCS alterations due to physiologic vari
time =0.26 ms, 2 standard deviations in distance 0.47 cm), ables to avoid potential sources of error.
the resulting calculations reveal up to a 10% error for a nerve
conduction velocity of 50 mls derived from an interstimulus dis Temperature
tance of 20 cm and an interstimulus time interval of 4.0 ms. This Temperature is perhaps the most important and prevalent phys
10% error for the presumed NCV of 50 mls (± 5 mls: 45 mls or iologic factor affecting NCS.17 A reduction in temperature in the
55 m/s) can be demonstrated by considering a distance mea upper limb below 32°C and in the lower limb below 30°C has sig
surement 2 standard deviation greater and less than a given nificant effects on NCS parameters and hence adversely affects
value (e.g., 20 cm) in combination with an interstimulus latency data interpretation. Although these temperature limits are some
± 2 standard deviations for time: what arbitrary, it is a good idea to ensure that reference data bases
and patients' limb recording sites achieve or exceed these levels.
Example A: NCV = (20 cm - 0.47 cm) -= The major sensory or motor waveform parameters affected in
(4.0 ms + 0.26 ms) = 46 mls clude latency. conduction velocity, amplitude, and duration.
Generalized vs. Focal Cooling. A reduction in temperature
Example B: NCV = (20 cm + 0.47 cm) -= may occur in two basic fashions: (1) focal cooling, in which
(4.0 ms -0.26 ms) =55 mls only the region surrounding the recording electrodes experi
ences a temperature reduction, or (2) generalized cooling,
These two examples illustrate that both time and distance which affects a major neural segment. Focal cooling occurs
errors can combine to generate a false-negative or false-positive when a small portion of the limb under investigation experi
result. A patient's mildly abnormal conduction velocity can be ences a reduction in temperature-as when the intrinsic hand
elevated into the low normal range, or a normal conduction ve muscles preferentially experience a reduction in temperature, or
locity can be decreased into the mildly abnormal range. The the digit is cold when antidromic sensory studies are performed.
above examples also point out that as the interstimulus distance Because cooling occurs over a focal segment of nerve-about
or time intervals decrease, the possible error also increases. the recording electrodes, for example-there is a small to moderate
Chapter IS ELECTRODIAGNOSTIC MEDICINE PITFALLS - 559
Negative
OrINt Peak spike Amplitude Hev
Figure 15-27. Focal ys. generalized cooling. Temperature LatenCy lAtency duration (ml)
(J.lV)
(mI) (ml)
The superficial radial nerve is examined with an an- (mI)
tidromic technique. A, A normal response is ob
tained with a limb temperature along the nerve and
at the recording site of 33°C. B, Focally cooling the
nerve about the recording electrode to lO°C white
A-A; 33°C 2.1 2.6 1.0 22.0 67
change in nerve conduction velocity and some degree of alter different values, and it is a good idea to take the necessary time
ation in distal latency with an increase in waveform duration to warm the limb as opposed to using variable correction fac
(Fig. 15-27). The potential's amplitude and rise time, however, tors, particularly in pathologic limbs. It is possible, therefore, to
can be significantly increased. FOCal cooling along the course of misinterpret these findings as indicating a generalized pathol
the nerve results in a SNAP amplitude reduction and prolonga ogy, such as a peripheral neuropathy, when indeed a warming of
tion of the waveform, effectively acting in a manner similar to the limb returns all values to normal. When a patient's limb is to
generalized cooling but over a smaller neural segment and be warmed, care must be exercised in all patients, but particu
hence with smaller effects. We also may consider the forearm larly in those with diminished sensation, because first- and pos
and hand to be reduced in temperature when the length of nerve sibly second-degree bums can occur if the patient is left
as well as the recording electrodes is subject to temperature al unattended or the limb is not closely monitored.
teration (Fig. 15-27). Whether recording motor or sensory nerve In most clinical situations, there is a differential degree of
conductions, the nerve conduction velocity and distal/proximal cooling along the course of the nerve, with the distal region
latencies can be expected to be reduced and prolonged, respec more reduced in temperature than the proximal segments. As a
tively, for generalized cooling. result, it may be possible to see a combination of focal and gen
The above findings probably are due to a decrease in the rate eralized cooling effects. Observing a large amplitude but pro
of sodium channel opening at the nodes of Ranvier, thereby re longed latency potential should raise the suspicion of
sulting in a longer time to generate a current density and hence temperature effects. It is always necessary to measure the pa
transmembrane voltage of sufficient magnitude to depolarize tient's limb temperature about the stimulating and recording
the adjacent node of Ranvier.6 A duplication of this reduction in electrodes and to warm the limb and recording region appropri
sodium channel opening time at all nodes of Ranvier along the ately. Simply measuring the ambient room temperature and as
. affected nerve segment produces a reduction in conduction ve suming that the patient is sufficiently warm to preclude neural
locity and prolongation of latencies. The temperature-affected temperature effects are unacceptable strategies.
sodium channels also are believed to exhibit a prolonged open
time where sodium inactivation is slowed. A cooled limb
demonstrates a SNAP or mixed-nerve action potential with an
increase in duration. The amplitude of the SNAP, however, may
decrease. A CMAP recorded from a cool limb also demonstrates
an increase in duration with no change or a slight decrease in
amplitude. In summary, a generalized cooling of the limb pro
duces an increase in the SNAP or CMAP duration and onset la
tency with a reduction in conduction velocity and possibly a
decrease or no change in amplitude compared with a warm
limb. I? The SNAP or CMAP amplitude may decrease because
of an increase in the temporal dispersion or arrival times for the
individual nerve fibers at the recording site, thus potentiating ~2mv
phase cancellation. This effect is less dramatic for CMAPs lhan 2ms
SNAPs because of the CMAP's longer potential duration and
hence larger tolerance for temporal dispersive effects. These pa Figure '5-28. Temperature effect on neuromuscular trans
rameters can be quantified. Median and ulnar motor nerve con mission.A 15% decremental response is observed for ulnar nerve
duction varies approximately by 2.4 m/s/oC, whereas the stimulation in a patient with myasthenia gravis with a limb temperature
peroneal, tibial, and sciatic nerves demonstrate the respective of 36°C (left trace). Cooling of the hand to 30°C results in both a
conduction velocity alterations of 1.8 mls/oC, 1.1 m/s/oC, and larger CMAP response and a reduction in the decrement to only 6%
1.9 mlsrc. n Distal motor latencies apparently change by ap (righttrace). (From Denys EH:AAEM Minimonograph #14:The influ
proximately 0.2 ms/oC for the peroneal, ulnar, and median ence of temperature in clinical neurophysiology. Muscle Nerve
motor nerve fibers. Various investigators have found slightly 1991; 14:795-431 I, with permission.)
560 - PART III PATIENT CARE-RELATED ISSUES
B_~_
not result in a CMAP equal to or greater than that for the proxi
mal site. If the current is elevated sufficiently at the wrist, a
volume-conducted current may activate the ulnar nerve at the
wrist, resulting in a CMAP comparable to that observed with
D~~5mv
A patient with a Martin-Gruber anastomosis and ulnar nerve
lesion in or about the distal arm or proximal forearm can have a
reasonable CMAP amplitude arising from the abductor digiti
mini or first dorsal interosseous muscles after ulnar nerve stimu 5ms
lation at the wrist but not at the condylar groove. This is because a
Figure IS.30. Apparent accessory deep peroneal nerve. A,A
lesion at the postcondylar groove spares fibers joining the ulnar
CMAP recorded from the EDB after peroneal nerve activation at the
nerve in the midforearm through the median nerve (most likely
ankle. B,An EDB CMAP after peroneal nerve stimulation at the fibular
the anterior interosseous nerve). The ulnar SNAP would be
head. C,A CMAP obtained from the EDB (same electrode as in A and
absent, because the Martin-Gruber anastomosis usually conveys
B) after tibial nerve stimulation at the ankle. D, Same active electrode
only motor fibers. The confusion caused by this finding can be re
used in three previous recordings detected a CMAP after stimulation
solved if the median nerve at the antecubital fossa is stimulated
posterior to the lateral malleolus. This finding may lead to the conclu
while recording from the ulnar-innervated hand intrinsic muscles.
sion that an accessory deep peroneal nerve is present when in fact the
Riche-Cannieu Anastomosis. The connection between the
tibial nerve is activated across the ankle by stimulating posterior to
deep branch of the ulnar nerve and recurrent branch of the
the lateral malleolus.
median nerve in the hand is called the Riche-Cannieu anastomo
sis or anomaly and may occur in up to 77% of the population. 43
This anastomosis probably accounts for the so-called "all-ulnar the lateral malleolus. After stimulation at this location, the two
hand" in patients who sustain a complete laceration of the amplitUdes (ankle plus posterior to lateral malleolus CMAPs)
median nerve but still have function of thumb abduction and op summate to approximate the CMAP amplitude obtained from
position. In such patients, stimulation of the median nerve at the proximal stimulation.
wrist fails to produce a thenar eminence CMAP, but ulnar nerve A potential pitfall regarding the accessory peroneal nerve
activation at any location results in a CMAP from the opponens should be considered. Anatomic investigation revealed that the
pollicis and abductor pollicis brevis muscles. Of course, all accessory deep peroneal nerve was present in 100% of speci
median SNAPs should be absent because the Riche-Cannieu mens and provided innervation to the peroneus brevis muscle
anastomosis is a motor, not a sensory connection. A combination and supplied presumably sensory branches to the ankle region. s7
of a Martin-Gruber and Riche-Cannieu anastomoses in patients Approximately 67% of specimens revealed a motor branch to
with a documented complete lesion of the ulnar nerve at the the lateral portion of the EDB. However, the accessory deep
elbow and median nerve at the wrist can result in little functional peroneal branch has been reported in 15-28% of persons exam
loss of either the median- or ulnar-innervated hand intrinsic mus ined by electrophysiologic means. 47,58.66 In the authors' experi
cles, but the median and ulnar SNAPs would be completely ence with routine performance of a peroneal nerve conduction
absent. If this anomaly is not considered, the above and possibly to the EDB, the electrophysiologic documentation of an acces
other clinicallelectrophysiologic scenarios can result in both sory deep peroneal nerve has been considerably less than
confusion and inappropriate medical investigations. 15-28% and certainly less than 67% of examined subjects. It is
Accessory Deep Peroneal Nerve. In some persons, a motor not uncommon to observe a smaller CMAP originating from the
branch from the superficial peroneal nerve, the accessory deep EDB when the peroneal nerve is stimulated at the ankle com
peroneal nerve, can travel posterior to the lateral malleolus to pared with the fibular head region. Increasing the current and/or
innervate a portion of the EDB.I8.4().62.75 A complete laceration of the stimulus pulse width at the ankle usually restores the CMAP
the peroneal nerve at the ankle or distal to the origin of the su amplitude. In the authors' experience, the peroneal nerve may
perficial peroneal nerve from the common peroneal nerve can be somewhat difficult to excite at the ankle, and optimal activa
result in absent ankle/toe dorsiflexion with continued function tion of the peroneal nerve requires an increase in the
in the EDB. Activation of the peroneal nerve at the ankle fails to current/pulse width combined with slight stimulator reposition
produce a CMAP from the EDB, but stimulation posterior to the ing. It is also not unusual for a strong stimulus delivered poste
lateral malleolus results in a reasonable CMAP. More com rior to the lateral malleolus to evoke an initially negative CMAP
monly, a large CMAP is documented from the EDB with stimu from the EDB. In effect, the delivered current activates the tibial
lation about the fibular head, but a considerably smaller CMAP nerve, which is just a few millimeters medial to the gastroc
with ankle stimulation. All efforts at supramaximal stimulation soleus tendon with respect to the stimulator's location laterally.
at the ankle fail to restore the CMAP to an amplitude compara The active electrode positioned over the EDB is also over the
ble to that produced by proximal stimulation. This finding can motor point for some of the foot intrinsic muscles, thereby gen
result in confusion unless stimulation is performed posterior to erating an initially negative CMAP to tibial nerve stimulation
562 - PART III PATIENT CARE-RELATED ISSUES
' • ulnar SNAP onset latency increased 0.3 ms. For this same group,
W
./ . . . •.. . -... ---.a-----o,,------ elderly persons had a O.4-ms increase in the mean median nerve
Cf)
a:
W
a..
50
..• ,
.'
.... ". ".~
, .. ,
.0........t
..
.,./:1. ... __ ••• __ ••• __ ••• __ ••• __ ••6.
A
onset latencies for sensory and motor studies. 34•44,45 In the lower
limb, age has little effect on H-reflex latency but results in ap
proximately 0.9-m/s per decade decrease for the sural nerve. 36•79 It
U)
a:
W40
, is a clinical impression that the H-reflex may be less likely to be
obtained in elderly persons, but a prospective study failed to doc
I
B A' .. -A Post tibial
W
• - - . Peroneal
ument this finding.36 The sural nerve response may be more diffi
::E
•••••••.• Ulnar cult to obtain, as is the peroneal nerve CMAP, in elderly persons,
0 - 0 Median but few multivariable control prospective studies substantiate
these impressions. When elderly persons are examined, particular
3 5 7 9 11 care must be exercised in controlling limb temperature because
YEARS OF AGE the common loss of muscle mass may predispose to cool limbs.
If children are examined, adult nerve conduction velocity
Figure 15-32. Nerve conduction changes from birth to child parameters for the different nerves cannot be used. In full-term
hood. Graphic representation of nerve conduction changes from birth infants, for example, nerve conduction velocities are approxi
to childhood. At about 5-7 years of age most children reach adult mately one-half adult values and eventually reach adult veloci
nerve conduction velocity values. (From Baer RD. Johnson EW: Motor ties by about 5-7 years of age (Fig. 15-32).49 Between birth and
nerve conduction velocities in normal children. Arch Phys Med Rehabil 5 years of age a rough rule is that infants and children have
1965:46:698. with permission.) nerve conduction velocities about one-half the adult values.
Chapter 15 ELECTRODIAGNOSTIC MEDICINE PITFALLS - 563
Gender
Gender has a small but significant effect on antidromic
median, ulnar, and radial SNAP parameters. Women appear to
B _.r-_
have larger amplitudes and shorter distal latencies (faster neural
conduction) for all three nerves.4.34.45.76 Ulnar distal motor latency
and nerve conduction velocities also are found to be faster in
women. These findings hold across all adult age groups. There is
little difference for median motor studies between men and
J200 V IJ
women. The reason for faster latencies and velocities in women 5ms
is unknown. Larger-amplitude antidromic digital SNAPs for
women are theorized to result from smaller digit circumference; Figure 15-33. Effect offacilitation on H-reflex. A,An attempt at
possibly a lower subcutaneous tissue-to-nerve tissue ratio favors evoking a flexor carpi radialis H-reflex fails regardless of pulse dura
comparatively elevated SNAP amplitudes. 4 •76 In the lower limb, tion and current intensities. A CMAP from the flexor carpi radialis
there appears to be no difference in SNAP amplitude, velocity, muscle is depicted with no hint of an H-reflex. B, Facilitating the re
or latency for the sural nerve in men and women. 79 sponse (gently flexing the wrist against resistance) results in the docu
mentation of an H-reflex despite the failure of all previous attempts to
Limb Length (Height) elicit this response without facilitation.
There is general agreement that lower limb length, height, or
axonal length influence nerve conduction studies. Most studies In the case of the lower limb H-reflex, gentle plantarflexion
have found a statistically significant slowing of nerve conduction may be required, whereas in the upper limb wrist flexion should
velocity directly proportional to limb length.10.64.68.76.81 For the be attempted. In particular, the flexor carpi radialis H-reflex
general range of body heights this effect is large enough to be often requires facilitation to observe this response properly (Fig.
clinically relevant. In body heights of 5.0-6.5 feet the average 15-33). In both lower and upper limbs, practitioners frequently
motor conduction velocity of the peroneal nerve ranges from fail to use this simple yet effective maneuver when an H-reflex
about 52--43 mlsJ1 These studies have been criticized for not cannot be obtained. As a result, it is possible to conclude that an
controlling temperature, which can have a profound effect on H-reflex is absent unilaterally or bilaterally when gentle facili
conduction velocity (see above). However, the proximal conduc tation can assist in the demonstration of a readily obtainable re
tion velocity of motor nerves over identical short and long axons, sponse. The act of facilitation should not affect the H-reflex
as measured by root stimulation, was also shown to be strongly latency. However, the central modulation so intimately involved
height-dependent, exclusive of temperature effect.81 Only one in this response may have an influence on the number of ante
study controlling for temperature failed to reproduce an inverse rior horn cells receptive to the afferent stimuli and hence the po
relationship between lower limb length and neural conduction tential's amplitude. Up to a 60% difference in side-to-side
velocity.79 There is general agreement that no correlation exists amplitude can be anticipated in normal persons; facilitation ef
between upper limb length and nerve conduction velocity.45 fects, however, were not taken into consideration.48 Latency ap
pears to be a relatively stable parameter and can be used
H-REFLEX AND CENTRAL MODULATION successfully to evaluate peripheral nerve disease. Amplitude
(FACILITATION) should be used with caution because of the large side-to-side
difference as well as profound central modulating influence.
Electrophysiologic investigation of the peripheral nervous Possible false-positive results can be observed because of fail
system with NCS deals exclusively with peripheral nerves ure to use agonist muscle facilitation properly or reliance solely
except for F-waves, and H-reflexes. The F-wave is an antidrorni on side-to-side amplitude differences.
cally induced subpopulation of backfiring motor neurons, Differentiation between an H-reflex and F-wave can be diffi
whereas the H-reflex effectively involves an electrically elicited cult in some patients. The F-wave usually is observed after the
sensory-motor reflex arc. Only a subpopulation as opposed to all CMAP in any skeletal muscle when supramaximal or near
available motor neurons is activated for F-waves, most likely be supramaximal current intensities are used. The H-reflex is typi
cause Renshaw cell inhibition plays some role. On the other cally recorded from the soleus muscle, but stimulating and
hand, the H-reflex is subject to both facilitatory and inhibitory recording from the tibial nerve also can generate F-waves. It is
central nervous system modulation acting on the motor neurons' possible to conclude that an H-reflex is present when instead
resting membrane potential. H-reflexes are recorded almost ex the F-wave is observed. The practitioner must distinguish H-re
clusively from the gastrocnemius-soleus muscle complex after a flexes and F-waves when the tibial nerve is excited and record
submaximal stimulus of long pulse duration (500-1000 ~s) is ings from the gastrocnemius-soleus muscle complex are
delivered to the tibial nerve at the popliteal fossa region. examined. H-reflexes are preferentially recorded when long
Frequently, an H-reflex can be recorded from the flexor carpi ra pulse durations and minimal current intensities are used. The
dialis and quadriceps muscles. Before assuming that an H-reflex cathode must be placed over the tibial nerve in the popliteal
is absent despite appropriately delivered electrical stimuli, it is fossa. Shifting of the cathode may be required to place the cath
necessary to attempt facilitation of the response by asking the ode in the optimal position, particularly in persons with signifi
patient to contract the examined muscle and its agonists gently. cant subcutaneous tissue. Care must be taken not to position the
Too large a muscle contraction or antagonist muscle contraction cathode too far laterally because the peroneal rather than the
can diminish and even abolish the H-reflex. tibial nerve can be excited. Foot plantarflexion, not dorsiflexion,
564 - PART III PATIENT CARE-RELATED ISSUES
INSTRUMENTATION FACTORS
The needle EMG portion of the electrodiagnostic medicine
consultation is not immune to potential errors. Needle type and
filters are two of the most commonly overlooked instrumenta
tion effects on motor unit action potential parameters.
Needle Type
Two types of needle recording electrodes, monopolar and
Figure 15·34. H-relfex. An H-reflex is recorded from a person concentric needles, are available for routine examination of
without known pathology. A, The recording depicts the recording of skeletal muscle. Both types of electrodes have electrical advan
an optimal H-reflex with its amplitude considerably larger than that of tages and disadvantages that are influenced primarily by practi
the preceding soleus CMAP. 8, Exactly reproducing the parameters in tioner preference and firSt exposure as opposed to absolute
A except that the patient is asked to contract the foot dorsiflexors criteria. Monopoiar needles are solid steel wires coated in
minimally.The result is a marked decline in the H-reflex amplitude and Teflon with a small area of metal exposed at the tip. The Teflon
slight latency prolongation. C-G,The current intensity is progressively helps the needle to pass through tissue planes with little "drag,"
increased with trace C continuing to demonstrate an acceptable H thus minimizing pain. The recording surface is essentially a
reflex. The response observed in trace D is likely a combination of an cone with a spherical recording region. The motor unit action
H-reflex and F-wave. Note that the CMAP is now significantly larger potentials thus have a characteristic amplitude, duration, and
than the presumed H-reflex. In traces E-G, multiple F-waves replace number of phases. Concentric needle electrodes consist of a
the H-reflex because of the continued current elevation. hollow cannula surrounding a thin, insulated nichrome wire that
serves as the active recording surface. The concentric electrode
is the desired response. The optimal current intensity elicits has a beveled end that produces a directional hemispherical
only an H-reflex without a preceding CMAP. An acceptable cur recording territory as opposed to the monopolar spherical
rent intensity produces an H-reflex with an amplitude greater recording territory. Some practitioners believe that the concen
than the initial CMAP (Fig. 15-34A). Caution should be exercised tric needle is comparatively harder to push through tissue be
if the presumed H-reflex has the same amplitude or a smaller cause of a "drag" on the surrounding tissue and thereby may be
amplitude than the CMAP, although it is unlikely that an F
wave can have the same magnitude as the CMAP. Some persons Table 15·3. Needle Electromyography Pitfalls
may be rather tense during the H-reflex examination and con Instrumentation factors
tract the foot dorsiflexors. Whenever the antagonist muscles to Needle type
foot plantarflexion are active, the H-reflex amplitude is de Filters
pressed and may even be absent (Fig. 15-34B). The practitioner
must ensure complete relaxation of the foot dorsiflexors or ever Physiologic factors
tors, and slight facilitation may be necessary to ensure the docu Insu1flcient anatomic knowledge
mentation of an H-reflex. The current intensity should be slowly Ar!QfTI'\lous innervation
increased with a stimulus rate not exceeding 0.5 Hz until the H Motor unit action potential parameters
reflex magnitude is maximized (Fig. 15-34C). Any further in Timing of examination
crease in current intensity results in the diminution of the Fasciculation potentials
H-reflex amplitude and creation of a larger CMAP than H ~ing
reflex, accompanied by a summated waveform that represents Distribution of abnormalities
Chapter 15 ELECTRODIAGNOSTIC MEDICINE PITFALLS - 565
~
low-frequency filter of 500 Hz.
0 10,000 500 400 4.2
.J2OOp.V
1ms
more painful. 70 A recent investigation comparing pain percep quantitative MUAP analysis is performed, a low-frequency filter
tion in patients examined with disposable monopolar and con setting of 2-3 Hz is commonly used because the reference data
centric needle electrodes revealed no significant difference base for MUAP duration was developed with this setting. It can
between the two electrodes. 79 • Gender did appear to influence be difficult to eliminate low-frequency noise, which can be quite
pain perception, with females noting higher levels of discomfort prevalent during the needle EMG examination. As a result, the
than males. low-frequency filter is typically elevated to approach 20 Hz, cre
Regardless of the pain issue, several objective recording charac ating a relatively stable baseline. The MUAP's initial and termi
teristics of the two electrodes should be understood. In concentric nal positive phases are composed preferentially of low-frequency
needle recordings, the cannula serves as the reference electrode subcomponent waveforms. The elevation of the low-frequency
and averages the recorded electrical activity over the amount of filter to 20 Hz or higher has the effect of delaying the potential's
metal located in the body. As a result, it is in close proximity to initial departure from and hastening its return to baseline, thereby
the central active recording surface. The electrical activity shortening the overall MUAP duration as well as slightly reduc
recorded at the surface is similar to that averaged over the can ing its amplitude. Further elevation of the low-frequency filter
nula, thus aiding in the cancellation of common mode signals. above 20 Hz results in continued distortion of the signal through
Concentric needle recordings tend to be electrically "quieter" amplitude reduction and duration shortening (Fig. 15-35).
than monopolar needle recordings because the cannula and High Frequency Filter. The MUAP's major spike is domi
active recording surface eliminate some data as a common nated to some degree by high-frequency subcomponent wave
mode signal, whereas the monopolar needle's reference elec forms because it occurs over a relatively short time. A
trode is located on the skin at some distance from the active high-frequency filter setting of 20,000 Hz or 10,000 Hz is com
recording site, thus diminishing common mode rejection. The monly used for performing either quantitative or qualitative
different recording montage (concentric needle: bipolar mon MUAP analysis. Both of these settings result in optimal MUAP
tage; monopolar needle: referential montage) of the two needles recordings with little waveform distortion. Reducing the high
also produces different motor unit action potential (MUAP) pa frequency filter level much b.elow 10,000 Hz can produce a re
rameters. As anticipated from the larger recording territory and duction in the MUAP's spike amplitude (Fig. 15-36). Extracting
referential montage, monopolar needle recordings reveal the MUAP's high-frequency components effectively eliminates
MUAPs with larger amplitudes because comparatively fewer data that lead to a reduction in MUAP amplitude. Of interest, a
muscle fibers are in proximity to the active recording surface
for the concentric needle recordings. MUAPs also may have
T.... ,......
more phases when recorded with monopolar needles, thus in
creasing the 10-15% polyphasic potentials normally recorded
with concentric needles to about 20-30%. The duration of
HIgh
FnIqUItIICy
..... (Hz)
Low
Ftwquency
".r(Hz)
~
lilY) ,....,
DurIIIIon
1.000
20
20
2,600
2.100
3.2
3.6
Low- and High-Frequency Filters
Low- and high-frequency filter settings for needle EMG stud O-J\- 500 20 1.500 3.8
ies are not discussed as frequently as for SNAP and CMAP
studies but are nonetheless important. The practitioner must be
...J 1.OOOIIV
2ms
aware of low- and high-frequency filter MUAP effects not only
for quantitative MUAP analysis but also for routinely performed Figure '5-36. High-frequency filter effect on MUAP.
qualitative analysis. Decreasing the high-frequency filter from 10,000 Hz to 500 Hz while
Low Frequency Filter. Recording a MUAP at different low keeping the low-frequency filter constant at 20 Hz results in profound
frequency filter settings demonstrates the effect that low-fre MUAP alterations (A-D). There is a progressive reduction in negative
quency filters can have on MUAP parameters (Fig. 15-35). When spike amplitude with a commensurate increase in MUAP duration.
566 - PART III PATIENT CARE-RELATED ISSUES
high-frequency filter setting below 2,000 Hz begins to docu fraught with potential diagnostic and anatomic pitfalls that can
ment a MUAP with a progressively increasing duration. The ab have serious consequences.
sence of high-frequency subcomponent waveforms allows the
remaining low-frequency waveforms to become predominant Anomalous Innervation
because they are no longer "balanced" by the higher-frequency Three anomalous innervations are of importance to potential
waveforms. Because low-frequency waveforms have longer du pitfalls in the needle electromyographic examination. Tbese
rations, the MUAP begins to appear more like a waveform pref anomalous innervations are the Martin-Gruber anastomosis,
erentially influenced by lower frequencies. Riche-Cannieu anastomosis, and the accessory peroneal nerve.
The anatomic and electrophysiologic consequences of these
PHYSIOLOGIC FACTORS three anatomic anomalies must be understood by all electrodi
agnostic medicine practitioners.
Insufficient Anatomic Knowledge Martin-Gruber Anastomosis. In addition to the possible
Lack of knowledge about the anatomic location of muscles nerve conduction errors arising from the Martin-Gruber anasto
and surrounding vital structures can lead not only to an erro mosis (see above), important needle EMG findings can result
neous diagnosis but also to significant adverse medical conse from this anomaly and may cause confusion, depending on the
quences for the patient. Locating a needle electrode into a lesion site. For example, a complete laceration of the ulnar nerve
desired muscle can be assured only if the practitioner is thor about the postcondylar groove should result in loss of ulnar-in
oughly familiar with surface anatomy. For example, the brachio nervated intrinsic hand muscle function accompanied by a so
radialis, extensor carpi radialis longus, and extensor digitorum called ulnar claw hand (hyperextension of the fourthlfifth
communis muscles are located in close proximity to each other metacarpophalangeal joints and flexion of the proximal and
on the forearm's extensor surface. A less than complete under distal interphalangeal joints to the same digits). Needle EMG ex
standing of where they are located can result in erroneous needle amination demonstrates an absence of MUAPs and florid mem
placement. Although all of the muscles are innervated by the brane instability in the affected muscles. A person with a
radial nerve, each contains different root innervations (brachio Martin-Gruber anastomosis, however, may retain variable and at
radialis, C5/C6; extensor carpi radialis longus, C6/C7; extensor times considerable hand intrinsic muscle function despite com
digitorum communis, C7/C8) and hence different neural path plete ulnar nerve laceration at the elbow, leading one to consider
ways through the brachial plexus. Failure to locate a needle elec the possibility of an "all-median hand." Reduced recruitment and
trode properly in the expected muscle can lead to considerable positive sharp waves/fibrillation potentials may continue to be
confusion over the proper anatomic location of a peripheral observed because the hand intrinsic muscles may be dually in
nerve lesion. A needle electrode should not be placed in a muscle nervated by both neural fibers traversing the anastomosis as well
unless the practitioner knows not only surface anatomy but also as the expected anatomic route through the ulnar nerve at the
how to demonstrate that the electrode is placed in the correct p0 elbow. The exact needle EMG findings depend on the extent to
sition by asking the patient to activate the desired muscle selec which each ulnar-innervated muscle receives neural innervation
tively, generating appropriate electrical activity. Of course, the from the crossover fibers compared with noncrossover fibers.
proper identification of specific muscles is insufficient for accu Failure to consider the possibility of a Martin-Gruber anastomo
rately localizing a lesion. The root level as well as neural path sis can lead to the conclusion that the ulnar nerve at the elbow is
through either the brachial or lumbosacral plexus, for example, not completely severed, suggesting an erroneous conclusion of
also must be appreciated. Additionally. the needle electrode good recovery when indeed the sensory (absent SNAP) and
should not be located in a muscle unless the practitioner can muscle innervation (flexor carpi ulnarislflexor digitorum profun
trace the muscle's innervation from the spinal cord level, through dus to digits four and five) may recover minimally, if at all.
specific regions of the plexus, about various potential entrapment Another problem may occur when a patient with a Martin
sites, and finally into the muscle. A comprehension of both accu Gruber anastomosis has an insult to the median nerve at the ante
rate localization of a muscle through surface anatomic land cubital fossa region or higher and experiences weakness in the
marks and complete anatomic innervation is necessary to avoid ulnar-innervated hand intrinsic muscles. Needle EMG examina
misdiagnosis as well as potential harm to the patient by piercing tion confirms membrane instability in a number or all of the
vital structures. hand's ulnar-innervated muscles. Failure to consider an anomalous
The needle electrode is placed into the body and hence pene connection between the median and ulnar nerves may result in the
trates both skin and multiple tissue planes. The practitioner conclusion of a combined median and ulnar nerve lesion. Both of
must be familiar with the various neurovascular bundles travers the above possible clinical scenarios should be kept in mind in ex
ing limbs, head-neck, and truncal regions. Piercing an artery or amining patients who present with either clinical or electrophysio
vein can be uncomfortable and lead to neural compression if the logic findings that appear confusing during initial examination.
bleeding is unchecked. Inadvertent vascular or aggressive Riche-Cannieu Anastomosis. An anatomic connection be
needle penetrations in a patient with pathologic or therapeuti tween the deep ulnar nerve and recurrent motor branch of the
cally induced clotting abnormalities can pose a medical risk. median nerve in the hand can lead to considerable diagnostic
Needle placement should be performed by persons who are fa dilemmas. For example, an ulnar nerve insult at the elbow can
miliar with these complications and prepared to deal with them result in positive sharp waves and fibrillation potentials in the
appropriately. Performing needle examinations about the neck median-innervated hand intrinsic muscles.24 In this instance, an
and thorax can lead to the induction of a pneumothorax. expensive and fruitless diagnostic work-up can ensue to look for
Attention to detail and anatomic knowledge is of particular im a brachial plexus or nerve root injury. In addition, a complete lac
portance whenever muscles about the clavicular and intercostal eration of the median nerve at the wrist in a patient with a Riche
regions are examined with needle electrodes. Exploring the ab Cannieu anastomosis may be the explanation for the so-called
dominal region in a less than expert fashion may result in pene "all-ulnar hand." Although positive sharp waves and fibrillation
tration of the peritoneal cavity. Failure to consider anatomy is potentials may be detected in typically innervated thenar muscles,
Chapter 15 ELECTRODIAGNOSTIC MEDICINE PITFALLS - 567
potential when it is really a pseudopolyphasic MUAP (Fig. 15 both temporally and spatially. In general, neurogenic processes
37). A trigger and delay line can serve the same purpose by produce a reduction in recruitment (decreased numbers of MUAPs
showing the same motor unit in the same place each time it fires fire rapidly at attempts at moderate to high force production),
with an occasional overlap with another MUAP briefly appear whereas myogenic processes result in an increase in recruitment
ing as a pseudopolyphasic potential. (many MUAPs fire normally or rapidly at low and high levels of
Duration is perhaps the most sensitive electrophysioiogic force). The normal physiologic response to increasing force gen
MUAP parameter that can be measured routinely. Other parame eration is for motor units to begin firing stably at about 5 Hz.
ters, such as MUAP area or turns analysis, may be sensitive to When the first recruited motor unit reaches a firing rate of about
pathology but require sophisticated computer-aided analysis. 10 Hz in response to increasing force production, a second motor
MUAP durations are essentially the same whether measured with unit begins to fire. The rate of firing for the first motor unit (10
concentric or monopolar needle electrodes, thereby permitting a Hz), divided by the number of motor units firing (2), results in the
similar database to be used for both types of electrodes. If MUAP so-called recruitment ratio of five. Theoretically, by dividing the
duration is to be used diagnostically, appropriate reference values firing rate of the first recruited motor unit by five, a predicted
must be used as well as reproduction of instrument settings. The number of observed motor units can be determined. If a myopa
MUAP's rise time is optimized (see above) by using a trigger and thy is present, multiple motor units fire at low force production,
delay line to ensure complete visualization of the entire MUAP. resulting in a recruitment ratio less than five. If more than one
At least 20 different MUAPs should be collected, making sure to motor unit is observed at low levels of force production with a
discard all polyphasic potentials; only nonpolyphasic MUAPs are firing rate less than 10 Hz (e.g., 7 Hz + 5 = 1.4 motor units), a
used for duration analysis. It is imperative to use a low-frequency myopathy may be present. For example, if a patient with a my
filter of 2-5 Hz because higher settings invalidate the MUAP's opathy contracts a muscle minimally and three distinct motor
duration with respect to widely used reference data. The use of units are present when the first recruited motor unit fires at 6 Hz,
other filter settings requires development of a new reference data the recruitment ratio is two. For a neurogenic disease, the first re
base. Elevating the low-frequency filter shortens the MUAP's du cruited motor unit may reach 20 Hz before the second motor unit
ration, which can predispose to recording short-duration MUAPs fires, producing a recruitment ratio of 10, which is larger than the
and concluding that a myopathy is present or reducing abnor anticipated ratio of five. Unfortunately, recruitment abnormalities
mally long-duration MUAPs into the normal range. are not a particularly sensitive parameter and, unless accompa
Recruitment is the sequential addition ofMUAPs with increas nied by more obvious signs of pathology. including positive sharp
ing levels of muscular force production. MUAPs are recruited waves, fibrillation potentials, and motor unit duration changes.
rarely occur as a sole abnormality.
It is easy to overinterpret motor unit recruitment findings, which
can result in a false-positive result. For example. a needle can be
located in the first dorsal interosseous muscle while a minimal
amount of force is produced. Slowing the instrument's sweep to 20
ms/div and recording the firing of motor units permits calculation of
a recruitment ratio. Interpotential spike duration of the first recruited
motor unit may reveal a time of 154 ms, which translates to a firing
A
rate of 6.5 Hz (Fig. 15-38A). Close inspection reveals that three ad
ditional MUAPs are present The recruitment ratio in this example
is 1.6 (6.5 Hz + 4 motor units 1.6), and the predicted number of
motor units is 1.3 (6.5 Hz + 5 =1.3 motor units) instead of the doc
umented four MUAPs. If only MUAPs close to the electrode are
included in the analysis on the grounds that distant volume-con
ducted motor units may flaw the results, similar results are obtained
J200lt V (Fig. 15-38B), One can conclude only that the observed recruit
20ms ment is myopathic and the patient has a myopathy. The patient is
normal, of course, suggesting a flaw in our reasoning. It can be
difficult for some patients to recruit only a single motor unit during
even minimal contractions. Moreover, distal as opposed to proxi
mal limb muscles are more prone to false-positive results with
the above technique. In short, if recruitment abnormalities,
particularly in distal limb muscles, are not accompanied by addi
tional needle EMG abnormalities, it is unwise to base a diagnosis
Figure 15-38. Monopolar needle recording In a normal Indi solely on recruitment findings. In the authors' opinion, false-positive
vidual's first dorsal interosseous muscle. A, Minimal contraction findings suggesting a myopathy are more common than false-pos
results in a large motor unit firing at about 6.S Hz with three addi itive results implying a neuropathy. A recruitment ratio exceeding
tional MUAPs between the first and second firing of the larger MUAP. five appears to have more diagnostic validity than a ratio less than
The first firing of the large MUAP is somewhat contaminated by a dis five. So-called "myopathic" or "early" recruitment is probably of
tant MUAP.The calculated recruitment ratio of 1.6 suggests a myopa limited diagnostic value for the above reasons.
thy is present. B. If only nearby MUAPs are included in the analysis, Observing the electrical activity after asking a patient to COD
similar results are obtained, suggesting that recruitment abnormalities tract a muscle maximally creates an interference pattern and is not
without concomitant needle electromyographic abnormalities should equivalent to recruitment analysis. An interference pattern rarely
not be used to formulate a diagnosis, especially those suggesting a provides useful information and can be subject to a false-positive
myogenic process. interpretation (i.e., incomplete obliteration of the baseline). This
Chapter 15 ELECTRODIAGNOSTIC MEDICINE PITFALLS - 569
:~-~~
the clinical context warrants.
When a brief train of positive sharp waves andlor fibrillation
3_~ ~_~ fibrillation potentials and positive sharp waves in the lum
4--\r---+~---.J100~V
~ lOInS
matic persons have been reported to have membrane instability
in the lumbosacral paraspinal muscles; a larger percentage of
these "abnormalities" are supposedly noted in older than in
younger subjects. It has not been the author's experience that
anywhere near 40% of persons with back pain (not all patients
Figure '5-42. Endplate spike activity. A monopolar needle elec with back pain have radiculopathy) or without back pain have
trode positioned in a normal muscle's endplate region records a true positive sharp waves and fibrillation potentials documented
number of endplate spikes characterized by their irregular firing rate. in the lumbosacral paraspinal regions. It is rather common,
Several endplate spikes display the stereotypical biphasic initially neg however, to document runs of positive sharp wave-like and fib
ative waveform (traces I, 2. and 3). However, endplate spikes resem rillation-like potentials in the cervical and paraspinal muscles,
bling both fibrillation potentials (trace 4) and positive sharp waves sometimes lasting for seconds at a time, particularly with a
(traces 1,2, and 4) also can be observed in the endplate region, which steady hand on the needle. These waveforms, however. usually
may lead to confusion about the mistaken presence of pathologic do not fire at a slow and regular rate that can be consistently re
positive sharp waves and fibrillation potentials. In practice, the needle produced when the electrode is removed and then repositioned.
electrode should be relocated away from the endplate to avoid diag The authors contend that reports of membrane instability in
nostic confusion. large percentages of asymptomatic persons are instead records
Chapter 15 ElECTRODIAGNOSTIC MEDICINE PITFAllS - 571
of atypical endplate spikes with triphasic (see Fig. 15-41) and The patient should be completely relaxed whenever sponta
initially positive biphasic (see Fig. 15-42) morphologies.31a This neous activity is examined.
is not to say that asymptomatic persons may not have a few pos Positive sharp waves indicative of nerve or muscle pathology
itive sharp waves or fibrillation potentials in the paraspinal mus can appear somewhat distorted with a sharp negative spike after
cles, particularly elderly subjects. It is certainly reasonable that the initial positive deflection with a terminal, wide-duration,
the older a person becomes, the greater the chance of having ex second negative spike (see Fig. 15-40). The initial sharp nega
perienced back pain at some time and possibly of having some tive peak and terminal long-duration negative phase are artifacts
degree of nerve root insult with variable degrees of axonal loss, resulting from the use of a 60 Hz notch filter. The 60-Hz notch
even though the patient is asymptomatic at the time of the ex filter converts the positive sharp wave's usually well-recognized
amination. Fibrillation potentials and positive sharp waves may long-duration negative phase into two distinct negative phases.
persist for years, and some muscle fibers may not have been This can be conceptualized as selective removal by the notch
reinnervated. Similarly, careful quantitative electromyography filter of frequencies approximating 60 Hz from the positive
may reveal altered motor unit action potential parameters in sharp wave. It is as if one were simply to take a piece of the neg
such patients. A slowly progressive axonal lesion of the poste ative phase out of the waveform, leaving behind the distorted
rior primary rami may result from ossification of the mamiI potential. In some instruments the positive sharp wave may
loaccessory ligament. 38 This issue continues to be debated}6,41 appear as a distorted, initially large positive, small negative
Hopefully continued research will lead to clarification rather biphasic fibrillation potential, particularly when the low-fre
than further obfuscation. quency filter approaches 30 Hz and the 60-Hz notch filter effec
The propensity for finding positive sharp wave-like and fib tively removes the terminal negative phase. In examining any
rillation-like endplate spikes in the small intrinsic foot and hand type of muscle activity during the needle EMG examination, it
muscles as well as the paraspinal region is probably due to the is recommended not to use the notch filter because both sponta
relative concentration of endplates and hence the ease of injur neous and voluntary activity can be significantly distorted.
ing muscle tissue while simultaneously provoking spontaneous
muscle fiber discharges. It is usually quite difficult to reproduce Endplate Spikes
these waveforms, and if they are not detected again, they should Endplate spikes can have the appearance of positive sharp
be ignored. In addition, the firing rate is usually, but not always, waves and result in a possible erroneous diagnosis. It is also pos
too rapid and irregular for positive sharp waves. Positive sharp sible for endplate spikes to have a biphasic negative/positive,
waves and fibrillation potentials fire relatively slowly and rarely biphasic positive/negative, or triphasic positive/negative/positive
exceed 20 Hz; they also fire quite regularly, making the distinc morphology (see Fig. 15-42). The generally accepted dogma that
tion between pathologically significant positive sharp endplate spikes are only biphasic and begin with a negative de
waveslfibrillation potentials and triphasic and positive sharp flection is false. Observing a small-amplitude, initially positive
wave-like endplate spikes relatively easy. Atypical endplate biphasic or triphasic potential is certainly possible and should
spike waveforms have been documented in the past 9 and re not cause confusion or be misinterpreted as a fibrillation poten
ferred to as "benign" fibrillation potentials.17 Therefore, fibrilla tial. The needle's orientation in the endplate zone can create end
tion-like potentials and positive endplate spikes are recognized plate spikes with all of the above morphologies (see Chapter 2).31
by their rapid, irregular firing rate and lack of reproducibility, If a low-frequency filter of 20-30 Hz is used during needle ex
all implying that they should be ignored and considered an "in ploration, the terminal positive phase of the more routinely ob
jured" endplate spike. Waveforms with the appearance of fibril served endplate spike can be somewhat truncated and elevated
lation potentials and positive sharp waves firing regularly and above the baseline, generating an endplate spi~e that is triphasic
relatively slowly, particularly if they are reproducible, should be (negative/positive/negative). The major pitfall of initially posi
considered as evidence of true membrane instability. Of course, tive endplate spikes is the conclusion that fibrillation potentials
these findings must be placed within the proper clinical context. must be present because of their initially positive deflection,
In the final analysis, the authors believe that it is certainly possi short duration, and small amplitUde. Close inspection of these
ble to find a few "true" positive sharp waves and fibrillation po potentials, however, reveals an irregular and rapid fIring rate, fre
tentials in muscles, indicating an unstable resting membrane quently accompanied by endplate spikes with an initial negative
potential, in asymptomatic persons, but there should be some deflection. If there is any suggestion that the needle electrode is
underlying reason without suggesting that these potentials are located in the endplate zone, it should be relocated to another
"normal" findings and should be ignored. Rather, they should region of the muscle to avoid confusion.
be commented upon and put into the proper clinical context,
like all electrodiagnostic findings. Age
Prolonged needle exploration, use of a needle with a spur on The process of aging affects not only NCS but also MUAP
the tip, or aggressive needle insertion into a muscle can result in morphology.30 As humans age, a gradual loss of anterior hom
the documentation of at least a few voluntary MUAPs with an cells results in subclinical denervation of muscle fibers innervated
appearance resembling pathologic positive sharp waves (see by the degenerating anterior hom celJ.5 The denervated muscle
Fig. 15-40). If the practitioner is unaware of slight muscle con fibers are reinnervated through the process of collateral sprouting.
traction and assumes complete relaxation, it is possible to con Collateral sprouting remodels the remaining motor units so that
clude that these potentials imply some type of nerve/muscle the number of muscle fibers per motor unit increases. The remod
pathology. Asking the patient to contract the muscle minimally eled motor unit displays somewhat different electrical character
should result in no alteration of the firing frequency of patho istics compared with its previous morphology.74
logic positive sharp waves but an increase in the firing of volun Over the ages of 1-85 years the MUAP's duration increases
tary MUAPs appearing as positive sharp waves. Similarly, from 5.7 ms (1-4 years) to approximately 10 ms (85 years).7,69
requesting the patient to relax completely results in disappear This increase probably is related to a greater degree of temporal
ance of voluntary MUAPs appearing as positive sharp waves. dispersion between the various single muscle fibers' summated
572 - PART III PATIENT CARE-RELATED ISSUES
electrical activity arising from the (1) differences in the arrival a particular region of muscle distant from the needle insertion
times of the nerve impulse to the individual single muscle site. It may be necessary to use several distinct needle insertion
fiber's endplates, (2) length of the region within which the end sites to explore a muscle fully in some persons. Anomalous
plates of the motor unit are situated, (3) propagation velocity of muscle innervation also can contribute to the failure to find
the different muscle fibers, and (4) length over which the single membrane instability in anticipated muscles or observe abnor
muscle fiber action potential propagates. In light of these histo malities in unanticipated muscles. Any or all of the above postu
logic changes of denervationlreinnervation with subsequent re lates (as well as others) may produce a false-negative needle
modeling of the motor unit, one may postulate a number of exploration in a given muscle. A complete radicular needle ex
reasons for increasing MUAP duration with age. Additional amination, therefore, should include several muscles from the
changes with aging include an increase in the MUAP's ampli same myotome that are innervated by different peripheral
tude as well as elevations in single-fiber EMG-measured jitter, nerves as well as multiple insertion sites within a single muscle
blocking, and fiber density (Table 15-4).73 to avoid the possibility of false-negative studies.
Failure to recall that MUAP duration and amplitude increase
with age may lead to an erroneous conclusion of abnormally
long-duration MUAPs, suggesting a neurogenic lesion in an el SOMATOSENSORY EVOKED
derly person. Similarly, if jitter, fiber density, or neuromuscular POTENTIALS (SEPS)
blocking is evaluated without considering the physiologic con
sequences of aging, a false-positive study may result when no Upper and lower limb SEPs are subject to a number of pit
neuromuscular disease is present. Sound reference data span fallsJ2 Two major categories of pitfalls include instrumentation
ning the human life-span must be used to avoid false-positive and physiologic factors. Practitioners using SEPs in the diagno
diagnoses. sis of peripheral or central nervous system disorders must be
fully cognizant of potential errors during the course of the elec
Distribution of Abnormalities trodiagnostic medicine consultation.
The anatomic distribution of EMG abnormalities due to a
nerve lesion theoretically follows the COllrse of neural innerva INSTRUMENTATION FACTORS
tion. For example, a C6 nerve root injury producing axonal loss
should result in positive sharp waves and fibrillation potentials, Surface/Needle Recording Electrodes
followed by MUAP abnormalities, in all upper limb muscles It has been suggested that surface electrodes should be used for
composing the C6 myotome. In reality, the membrane instabil all recording sites when any type of evoked potential is obtained.
ity or MUAP abnormalities is rarely documented in all muscles Objection is raised to subdermal needle recording electrodes, pri
of a particular myotome. The reason for this finding is unclear, marily on the grounds of higher impedances and risk for infec
but a number of factors probably are involved. Each limb tion. The issue of higher impedance is irrelevant because once the
muscle typically is innervated by two and occasionally three electrode is located under the skin (within the body), the signifi
nerve root levels. It is likely that individual muscles have a pre cantly higher amplifier input impedance ensures adequate signal
dominant innervation by a single root level with variable degree reproduction. Infection has not been objectively documented. Of
of innervation from the remaining levels. A C6 nerve root insult, greater concern is the proper sterilization of all SEP electrodes
therefore, may generate membrane instability in the supra/infra because skin impedance must be reduced by either abrasion or
spinatus, biceps brachii, extensor carpi radialis, and pronator use of needle electrodes, thereby exposing both surface and
teres muscles, but little in the way of abnormalities in the del needle electrodes to the patient's serum. In short, there is no dif
toid and flexor carpi radialis muscles because of a variable ference between surface and needle recording electrodes with re
degree of C6 innervation in these two muscles in the patient spect to SEP waveform amplitude or latency.26
under investigation. A patient may have a prefixed or postfixed
brachial plexus, altering the percentage of expected nerve root High- and Low-Frequency Filters
levels in various muscles. In addition, the number ofaxons un Filter effects can be quite prowinent for SEP waveforms,
dergoing wallerian degeneration may be small and localized to just as they are for SNAP, CMAP, and MUAP potentials. As
Chapter 15 ELECTRODIAGNOSTIC MEDICINE PITFALLS - 573
High Low
Prwquwtcy
........ (Hzl
~
FlIer (Hz) "
e-I e-,
N, Amplitude
(JIV)
noted above, the use of a reference database mandates replica consequences by shortening the peak latencies and reducing the
tion of the low- and high-frequency filter settings under which SEP's amplitude.
the normal values were determined. Inappropriate filter settings High-Frequency Filter. As noted above, the predominant
can profoundly affect the SEP waveform and hence the pa frequency content of the SEP appears to be below 30 Hz.
tient's diagnosis. Without doubt some high-frequency subcomponent waveforms
Low-Frequency Filter. The SEP waveform occurs over a are contained in SEPs, and the best way to explore to what
relatively long period from initiation to termination and thereby degree is to examine the effects of lowering the high-frequency
is dominated primarily, but not exclusively, by low-frequency filter while keeping the low-frequency filter constant (Fig. 15
subcomponent waveforms. Because of the significant amount of 44). The previous example suggests that a low-frequency filter
low-frequency subcomponent waveforms, elevating the low-fre of 10 Hz should not distort the waveform too much. Low-fre
quency filter has an important effect on the SEP waveform. quency filter settings of 1 Hz are not a good idea because they
As for sensory and motor studies, the effects of altering the permit low-frequency noise, such as wire or electrode move
low-frequency filter on the waveform can best be exemplified ment, to interfere with the desired signal and 10Hz appears to
by recording a cortical SEP with different low-frequency filter be a good compromise between minimizing noise and adversely
settings while maintaining the high-frequency filter at a set level affecting the SEP. There is little practical difference between a
(Fig. 15-43). Beginning with a low-frequency filter of 1 Hz es high-frequency filter setting of 3,000 Hz and 500 Hz from the
sentially permits all of the low-frequency subcomponent wave perspective of measuring significant SEP waveform parameters.
forms to contribute to the SEP. Increasing the low-frequency The advantage of using a low-frequency filter setting of 1,000
filter by a factor of 10 has a mild effect of shortening the wave Hz or 500 Hz is the elimination of high-frequency noise in the
form's peak latency and lowers the SEP's amplitude minimally. signal that emanates from the instrument or environment. Fewer
A low-frequency filter setting of 30 Hz produces continued averages may be necessary to produce a "quiet"-appearing SEP.
peak latency shortening and significant alteration in amplitude. Lowering the high-frequency filter below 200 Hz is not recom
When the low-frequency filter is set at 100 Hz, the SEP is mended because the potential's low-frequency subcomponent
almost completely obliterated. In short, increasing the low-fre waveforms begin to be eliminated, which adversely effect the
quency filter to about 30 Hz or higher begins to have profound SEP's parameters of interest.
e-, (-,
HIgh Low Ampllb. .
FnIquIncr
P, H,
Prwquwtcy (JIV)
FIIIf(Hz) FIIMr(Hz)
0 CONCLUSION
There are many more electrodiagnostic medicine pitfalls than
Jf,OOo.lV those mentioned in this chapter. The more common and particu
larly vexing pitfalls are discussed in detail, but, the astute prac
f.OOOms
tioner should be prepared to deal with any problem that may
E lead to a false-positive or false-negative impression. Perhaps the
greatest electrodiagnostic medicine pitfall is when the examina
tion is performed by practitioners not expertly trained in either
Fl,ure 15-47. Sympathetic skin response. A-C. Sympathetic the diagnosis of neuromuscular diseases or their electrophysio
skin response from the upper limb following median nerve excitation logic appearance. It is far too easy for unqualified persons
at the wrist. Note the large degree of variability among three sequen simply to purchase an instrument and begin evaluating patients
tial stimuli. D, Elevating the low-frequency filter to Hz profoundly with possible neuromuscular disorders. Aside from this obvious
alters the response. E,A deep inspiration before stimulating the nerve shortcoming, even the expert practitioner must be aware of pit
can result in potentiation of the waveform. falls that may lead to suspect diagnoses. Expert practitioners
576 - PART III PATIENT CARE-RELATED ISSUES
must understand thoroughly both the merits and shortcomings 28. Dumitru 0, Newton BY. Dreyfuss P: Segmental vs dermatomal somatosensory
evoked potentials: Normal intertrial variation and side-to-side comparison. Am J
of any diagnostic consultation. The practitioner is encouraged Phys Med RehabiI1993;72:75-83.
to reproduce the artifactual findings discussed in this chapter to 29. Dumitru D. Jewett DL: Far-field potentials. Muscle Nerve 1993;16:237-254.
be familiar with their presentation and method of correction. An 30. Dumitru D. Gershkoff A, Walsh NE: Peripheral NervouslMuscular System. In
awareness of these pitfalls can assist in the formulation of ap Felsenthal G, Garrison SJ, Steinberg FU (eds): Rehabilitation of the Aging and
Elderly Patient. Baltimore, Williams & Wilkins. 1994, pp 227-241.
propriate and accurate diagnoses. 31. Dumitru D, King JC. Stegeman OF: Endplate spike morphology: A clinical and
simulation study. Arch Phys Med Rehabil 1998;79:634-640.
31a. Dumitru D, Diaz CA, King JC: Prevalence of denervation in paraspinal and foot
intrinsic musculature, Am J Phys Med Rehabil (in press).
ACKNOWLEDGMENT 32. Eisen A, Purves S Hoirch M: Central nervous system amplification: Its potential
in the diagnosis of early multiple sclerosis. Neurology 1982;32:359-364.
The author thanks John C. King, M.D., for help in defining the 33. Eisen A: Electrudiagnosis ofradiculopathies. Neurol Clin 1985;3:495-510.
potential sources of error resulting from distance and time mea 34. Falco FJE, Hennessey WJ, Braddom RL, et al: Standardized nerve conduction
studies in the upper limb of the healthy elderly. Am J Phys Med Rehabil 1992;
surements and collecting the data used as illustrative examples. 71 :263-271.
35. Falck B, Alaranta H: Fibrillation potentials. positive sharp waves and fascicula
tion in the intrinsic muscles of the foot in healthy subjects. J Neurol Neurosurg
Psychiatry 1983;46:681-683.
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227-235. 79a. Walker WC, Keyser-Marcus LA. Johns JS, Steel RT: Relation of e1ectromyograpbic
70. Sherman HB, Walker FO, Donofrio PD: Sensitivity for detecting fibrillation po induced pain to type of recording electrodes. Muscle Nerve 2001 ;24:417-420.
tentials: A comparison between concentric and monopolar needle electrodes. 80. Wiechers D. Guyton JD. Johnson EW: Electromyographic findings in the extensor
Muscle Nerve 1990;13:1023-1025. digitorum brevis in a normal population. Arch Phys Med RehabilI976;57:84-85.
70a. Simonetti S: Electrophysiological study of forearm sensory fiber crossover in 81. Zwarts MJ. Guechev A: The relation between conduction velocity and axonal
Martin-Gruber anastomosis. Muscle Nerve 2001;24:380-386. length. Muscle Nerve 1995;18:1244-1249.
PART
IV
CLINICAL
APPLICATIONS
Chapter 16
Neurons
Daniel Dumitru, M.D., Ph.D.
Anthony A.Amato, M.D.
CHAPTER·OuTLtNI
This chapter primarily addresses disorders involving the motor fibers originate in various regions of the cerebrum consti
upper and lower motor neurons and portions of the central ner tuting .the motor cortex that forms the corticospinal or pyrami
vous system (CNS) that can be readily evaluated with routine dal tract (Fig. 16_1).291 After descending througb the posterior
electrodiagnostic medicine techiliques. Cortical and subcortical limb of the internal capsule and mid-portion of the crus cerebri,
disorders also are discussed, but only from the perspective of these fibers form into readily recognizable fiber bundles to form
abnormalities capable of being detected with the more routine the medullary pyramid. Before leaving the medullary region,
electrodiagnostic techniques. Somatosensory evoked potentials the vast majority of these corticospinal fibers decussate to con
(SEPs) are also mentioned, primarily with respect to alterations stitute the pyramidal decussation. Upon reaching the upper
generated by spinal cord pathology. cervical region, a relatively well laminated (medial to lateral
layering of cervical to sacral fibers respectively) composition of
these fibers form the well-known lateral corticospinal tract
SPINAL CORD ANATOMY (Fig. 16_2).619 At each segmental level, the most medially lo
cated fibers depart the tract to synapse with interneurons in the
It is worth reviewing the basic anatomic relationship of the lateral regions of the ventral horn. The interneurons in turn then
major pathways and cell columns comprising the spinal cord synapse with alpha motor neurons and gamma motor neurons.
prior to considering the clinical and electrophysiologic aspects A few fibers from the corticospinal tract, those subserving fine
of disorders affecting this region of the body. For the purpose of motor skills performed by muscles in the hands and feet, bypass
this discussion, we can consider the various relevant compo the interneurons and directly synapse with their respective ven
nents of the spinal cord as consisting of descending motor (ef tral nuclei. A small portion of fibers (approximately 10% or
ferent) and ascending sensory (afferent) pathways. less) comprising the corticospinal tract do not decussate in the
medullary region and continue to descend ipsilaterally (ventral
EFFERENT PATHWAYS corticospinal tract), but upon reaching appropriate segmental
levels then decussate through the anterior white commissure to
The end result of essentially all voluntary skilled motor path synapse with their respective interneurons or motor neurons.
ways is to exert control over skeletal muscles. Descending The above noted corticospinal fibers as well as interneurons
581
582 - PART IV CLINICAL APPLICATIONS
FRONTAl LOBE
FACE
JAW
LIPS
TONGUE
PONS
UPPER
Pyr.....1CNI1
IEDULLA
pathway to lev
P-'v-
touch sensatIOn
LOWER
(r.'ays up Ind
down,ndorul
MEDlA.LA
Orey and across
to aoposne ventraf
splnotNlarnec
Iract)
Motor Unit
Probably relays
into the reticular
these modalities is the lateraJ spinothalamic tract (Fig. 16-6). making it difficult to eliminate pain sensation completely by
After entering the spinal cord via the dorsal root ganglion cell simply ablating the lateral spinothalamic tract. The second
region. these nerve fibers usually ascend 1 and possibly 2 or 3 order neuron traversing the lateral spinothalamic tract ascends
spinal segmental levels to then cross ventral to the spinal canal to the thalamus, and from there a third-order neuron may pro
(ventral white commissure) and coalesce in the ventrolateral ject to the primary somatosensory cortex. The primitive nature
aspect of the spinal cord, thereby forming the above-noted lat of the pain pathways means that there are multiple other inter
eral spinothalamic tract. An interneuron may be interposed in connections between the main pain pathway and various other
this area, thus giving rise to a second-order neuron to ascend in nuclei throughout the neuraxis. Other tracts also convey deep
the above noted tract. The fibers from the sacral regions are lo and visceral pain sensations.
cated lateral to those from the lumbar that are lateral to the tho
racic fibers, etc. The final fiber arrangement is that of a
lamination whereby the cervical fibers are most medial with the PATHOPHYSIOLOGIC REACTION TO
sacral fibers most lateral. There are several important aspects to SPINAL CORD INJURY
this basic anatomic arrangement. First, a lesion at any level not
affecting the most posterolateral aspects of the spinal cord usu In this chapter, the primary concern is spinal cord insult with
ally does not result in a loss of pain or temperature to that level. resulting peripheral motor nerve findings and disruption of cen
For example, a lesion of the lateral spinothalamic tract at TS tral afferent neural conduction. The peripheral aspects of the
does not produce reduced pain and temperature discrimination sensory system are unaffected by central nervous system injury.
at TS, but results in a reduction or absence of this modality from This is because the sensory nerves' cell bodies, dorsal root
about 17 or T8 and below contralateral to the side of the lesion. ganglion, are located outside of the spinal cord. Contained
This is because at the TS spinal level the fibers from 17 or T8 within the dorsal root ganglion are the cell bodies for peripheral
are just crossing over to join the lateral spinothalamic tract. and central extensions of the first-order neurons. As a result, the
Also, the distribution of sensory fibers, medial (cervical) to lat intact cell bodies continue to supply the metabolic requirements
eral (sacral), gives rise to the concept of sacral sparing. In of their peripheral extensions. Unfortunately, a lesion in the
brief, a lesion disrupting the central regions of the spinal cord spinal cord that disrupts continuity between the dorsal root gan
but sparing the outer margins results in relative sparing of the glion's cell body and the sensory axon's more rostral extension
tracts mediating both motor and sensory fibers that arise from results in degeneration of the isolated neural portion within the
and descend to the sacral regions; hence the term sacral sparing. central nervous system. This is because the lack of axonal conti
The fibers for pain and temperature can also enter the spinal nuity prevents the cell body from supporting the metabolic de
gray regions after crossing from the contralateral side, thus mands of the sensory axon's central aspect.
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 585
A loss of anterior horn cells has rather devastating conse reveals a characteristic finding. The elbow and Erb's point
quences on the functioning of the body segment they innervate. recording sites demonstrate normal waveforms with respect to
Once the alpha motor neuron is rendered nonviable, its periph latency, amplitude. and interpotential time intervals. Recordings
eral extension, the axon, undergoes Wallerian degeneration with from C2 and C3', however, should reveal no definable wave
resorption of the endoneurial contents and myelin sheath. As forms. These findings are associated with normal median and
anticipated, once the anterior horn cell is disrupted or degener ulnar SNAP responses as obtained from routine electrodiagnos
ates, the single muscle fibers innervated by the alpha motor tic medicine techniques. Of course, the patient has loss of poste
neuron are rendered denervated. These muscle fibers are no rior column sensation ipsilateral to the lesion at all locations
longer under voluntary or reflex control, and the patient's distal to the C4/5 level. Performing SEPs on the right limb re
strength is subsequently reduced. A progressive reduction in sults in normal waveforms at all recording locations along the
more and more alpha motor neurons eventually results in right limb, C2, and the contralateral somatosensory cortex (C4').
muscle weakness with paralysis present when there are insuffi The SEP findings are consistent with a lesion proximal to Erb's
cient numbers of motor neurons remaining to move the affected point but distal to C2. The fact that a waveform can still be
body part. The manual muscle test is a rough guide to the degree recorded implies that the sensory fibers distal to the dorsal root
of axonal loss; however, it is not possible to exactly quantify the ganglion are intact and thus a central nervous system lesion is
manual muscle test with a number of remaining anterior horn likely present. A normal peripheral SNAP finding confirms this
cells in humans. When muscle tissue is no longer innervated, it impression.
begins to atrophy with a clinically observed reduction in muscle Abnormal motor nerve conduction findings are not present
bulk. unless the alpha motor neurons or their peripheral extension are
The above pathophysiologic reactions are rather simple but injured. A reduction in or loss ofaxons does not appreciably
suffice to form a foundation upon which the remainder of this affect the rate at which the remaining axons conduct an electri
chapter relies. A consideration of the neural consequences aris cal impulse unless the fastest conducting fibers are preferen
ing from a loss of alpha motor neurons and central conducting tially injured. The only reason for a reduced rate of conduction
afferent pathways permits one to contemplate the electrophysio as measured with routine techniques is a commensurate loss in
logic correlates of neural dysfunction. the fast conducting fibers. In most disorders of the motor
neuron, peripheral neural conduction velocity is well main
tained and is not reduced by more than 20--30% of the normal
ELECTROPHYSIOLOGIC CORRELATES mean conduction velocity for the nerve under consideration.
OF SPINAL CORD INJURY There is a corresponding loss of muscle bulk secondary to the
previously noted reaction of muscle atrophy. Loss of muscle
Insult to the central afferent pathways or alpha motor neurons bulk can result in a physiologic reduction in neural conduction
can result in electrophysiologic abnormalities detectable with secondary to a drop in the affected limb's temperature simply
electrodiagnostic medicine testing. The exact electrodiagnostic because of the loss of muscle mass and its vasculature. If there
medicine findings are dependent upon the location of injury, is a relatively small degree of motor neuron loss, the process of
severity of insult regarding the number of dysfunctional neu collateral sprouting can reinnervate the neighboring denervated
rons or fibers contained within a tract, and timing of damage muscle fibers and maintain both muscle power and bulk. In this
with respect to the examination. As the number of damaged case, the compound muscle action potential (CMAP) is well
tracts or neurons increases, corresponding clinical and electro preserved and continues to be within the limits of normal. As
physiologic deficits as well as prognosis can also be anticipated more and more alpha motor neurons are lost, however, there
to worsen. comes a point at which the compensatory collateral sprouting
From the perspective of the afferent aspect of the nervous capacity of the remaining anterior hom cells is exceeded. In this
system, a distinction must be made between strictly peripheral case, a corresponding drop in the muscle's CMAP is detected.
conduction techniques (e.g., sensory nerve action potential) This assumes a slowly progressive process where failure of
and combined peripheral and central neural conduction, i.e., reinnervation results in a drop in the CMAP magnitude. If there
SEPs. If a lesion is located at some point proximal to the dorsal is an acute loss of motor neurons, the drop in CMAP amplitude
root ganglion, e.g., sensory root avulsion or spinal cord is noted within several days of the insult. The distal motor la
damage, the peripheral extension of the sensory nerve remains tency is not greatly affected by a reduction in the motor neuron
intact. As a result, the patient will have completely normal population. As the amount of motor neurons decline, however,
SNAP amplitudes, conduction velocities, and any other sensory there is a reduction in the number of observable F-waves.
parameters measured over the affected segments. These find Because there are only a few motor neurons activated from the
ings are noted despite clinical abnormalities suggesting pro large alpha motor neuron pool under normal conditions during
found loss of sensation. The findings are consistent with the F-wave studies, an overall reduction in the available motor neu
above-discussed principles of a normal peripheral sensory rons must result in a reduced frequency and amplitUde of F
nerve axon remaining as long as its parent cell body in the wave observed.
dorsal root ganglion is preserved. In addition to the above-noted neural conduction abnormali
At any point rostral to the central nervous system insult, how ties, the needle electromyographic examination can also reveal a
ever, the central extension of the sensory neuron degenerates. number of interesting findings. As the number of motor neurons
SEPs can best demonstrate the electrophysiologic correlate of is reduced, there are fewer remaining to continue to serve the
this type of insult. Let us suppose the posterior column region function of activating and controlling skeletal muscles. This im
on the left at the C4/5 level is profoundly damaged. Stimulating plies that the body must functionally compensate for the reduced
the median and ulnar nerves at the left wrist while recording alpha motor neuron pool. The remaining motor units only have 2
from the median and ulnar nerves at the elbow, Erb's point, C2 ways of making up for lost comrades with respect to force re
spinous process, and contralateral somatosensory cortex (C3') quirements, i.e., temporal and spatial recruitment. Most motor
586 - PART IV CLI NICAL APPUCATIONS
units begin firing at about 3-5 Hz but reach stable firing rates the various pathways affected and hence the lesion. When the
only at approximately 5-6 Hz. As more force is required, the ini posterior columns are affected, patients may complain of a con
tially recruited motor unit action potential (MUAP) can be ob stant tingling resembling a fine vibratory sensation distal to the
served to increase its firing rate. Upon reaching 10-12 Hz, a affected region. Additionally, a constricting feeling may be
second motor unit is recruited. The increase in firing rate of the noted as if a wide cloth band were being slowly tightened about
first MUAP is an alteration in the temporal firing or recruitment the chest, stomach, knees, or ankles. When clothes or other .ob
of the motor unit. When the second motor unit begins to fire, it is jects touch the skin, the patient may describe the touch as if it
spatially recruited to assist in the development of more force. If was occurring through several layers of clothing, Le., dull and
the second motor unit is damaged, the first motor unit may need distant, or as if the skin is being pulled taut. A demyelinating or
to increase its firing rate to 15-20 Hz before a third motor unit compressive lesion of the posterior columns can result in a tin
can be recruited. In persons with a reduction in the number of gling sensation beginning in the neck region and radiating into
anterior hom cells, an alteration in MUAP recruitment can be the upper and lower limbs following a rapid flexion of the neck,
observed in the affected segments. Specifically, when the af i.e., Lhermitte's sign. This is a nonspecific finding indicating
fected muscles are examined, there are fewer than normal motor an irritation of the posterior column pathways. A lesion within
units firing at rapid rates, i.e., reduced recruitment. After an ap the substance of the spinal cord affecting the spinothalamic
propriate time period has passed, 5-14 days in most cases, posi fibers results in a poorly localized deep aching sensation about
tive sharp waves and fibrillation potentials can be observed in the involved segment with a diffuse and nonfocal radiation. It is
the muscle supplied by the injured neural segments. also possible for the patient to describe a more superficial sen
If there are remaining viable alpha motor neurons, the above sation of a burning yet icy feeling on the skin. Frank numbness
described process of collateral sprouting begins to take effect in is usually not an initial symptom of intrinsic spinal cord pathol
order to compensate for the decreased number of functioning ogy, particularly during the early course of the disease process.
muscle fibers. This process tends to remodel the motor unit by Many times the symptoms can lead to an early diagnosis of the
increasing the number of muscle fibers per motor unit. A patient's pathology.
number of electrical consequences can be observed as a result In addition to the sensory pathways, it is also possible for
of this process. Initially, the newly formed collateral sprouts are either the descending motor pathways or alpha motor neurons
connected to the muscle fibers with tenuous neuromuscular to be affected. When the alpha motor neurons are rendered dys
junctions that have an increased variability in producing a functional, the innervated muscles usually begin to atrophy.
suprathreshold end-plate potential. The reduced end-plate Patients may not complain of weakness when the lesion is small
margin for transmission or safety factor results in an increase in or during the early course of the disease unless the affected
jitter as measured with single-fiber electromyography. Similarly. neural segments innervate the intrinsic muscles of the hands. In
if collateral sprouting occurs. there is an increase in the fiber this case, patients may note a decrease in manual dexterity and
density. An increase in the number of muscle fibers per motor an alteration in activities of daily living requiring fine motor co
unit results in MUAPs with increased amplitUdes, durations. ordination. If relatively large muscle groups concerned with
and phases. The amplitude increases simply because more volt gross activities are involved (gastrocnemius-soleus/foot plantar
age is generated with each motor unit discharge secondary to flexion), it may require significant loss of muscle function prior
more muscle fibers under control of the anterior hom cell. to the patient noting any difficulty. On the other hand, when the
MUAP duration is increased as there is more temporal disper disease process is fairly extensive or rapidly progressive, a re
sion between the first and last activated single muscle fibers re duction in function such as climbing stairs, arising from a low
sulting from a greater spatial distribution of muscle fibers and chair, or performing overhead activities may be noted. Not un
reduced conduction in the newly formed collateral sprouts. commonly, when the tibialis anterior muscle is affected, the pa
Also, there are more muscle fibers, and hence. more voltage tient may describe an increased frequency of tripping over
generated per motor unit, which permits the detection of an ear uneven pavement or small undulations in a carpeted and later
lier departure from, and comparatively later return to baseline. uncarpeted floor. Patients with lower motor neuron involvement
Reduced temporal synchrony also results in MUAPs with more also frequently complain of fasciculations and cramping.
phases. With time, there is maturation of the collateral sprouts If the upper motor neurons are involved, patients develop
and the degree of MUAP duration and phase increase may di spasticity. Patients with spasticity of the legs may describe an
minish somewhat; however, the MUAP amplitude may increase increasing difficulty ambulating. The legs appear as if they were
as a result of this improved synchrony. "stiff" with an associated increased incidence of tripping. Fine
motor movements are slowed. If the patient steps down onto the
pavement or descends a flight of stairs rather forcefully, the foot
ELECTRODIAGNOSTIC MEDICINE may begin to flex and extend uncontrollably, i.e., demonstrate
EVALUATION clonus. Over time. the patient may note that the anterior portion
of the shoe is excessively worn secondary to a stiff-legged walk
HISTORY AND PHYSICAL EXAMINATION ing style.
Unlike sensory examinations, patients can have muscle wast
In patients with progressive involvement of various aspects of ing but not necessarily be aware of the problem if it occurs
the motor and sensory tracts/nuclei within the spinal cord, a slowly and is in a noncrucial region with respect to activities of
number of symptoms and signs can be expected depending daily living. As alluded to above, when there is loss of the alpha
upon the lesion's location. A careful history is essential to inter motor neurons, the muscle fibers innervated by the correspond
pret the patient's symptoms accurately. It is often difficult for ing peripheral nerves atrophy, which can be appreciated clini
patients to accurately describe the annoying symptoms that they cally particularly when it is asymmetric. If there is a lesion at
are experiencing. The examiner must attempt to fully under some point in the central nervous system. those regions of the
stand what the patient is describing. as this can offer insight into spinal cord below the lesion are no longer under the "nonnal"
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 587
(Werdnig-Hoffmann Disease)
As directed by the history and physical examination with re Clinical Features. SMA I, Werdnig-Hoffmann disease, man
spect to the most appropriate muscle or muscle groups exam ifests within the first 6 months of life (Table 16-1 ).214.334.319.603.803
ined, a needle electromyographic examination can be quite About 30% of patients manifest in utero with decreased fetal
valuable. In lesions with significant loss of motor neurons, the movements. The incidence is approximately 1 in 25,000 live
earliest finding is a reduced recruitment of MUAPs. Fewer births with males and females being equally affected. 620 The clin
MUAPs firing at fast rates is compatible with lower motor ical features are explained by the loss of anterior horn cells and
neuron drop out or axonal loss; however, the recruitment may be cranial motor nuclei (Fig. 16-7). Infants manifest with severe
nonnal in mild lesions. Within several weeks, positive sharp generalized weakness and hypotonia. There is minimal sponta
waves and fibrillation potentials are of value in documenting the neous movements except in perhaps the hands and feet. Because
distribution of the lesion. It is also important to document the of the generalized weakness, infants assume the so-called frog
presence or absence of voluntary MUAPs. As long as there are leg posture with their hips abducted and knees flexed. Extremely
MUAPs, this implies that the lesion is incomplete with some poor head and trunk control are noted, and infants never demon
sparing of motor neurons. Fasciculation potentials can be present strate an ability to roll over or flex their heads off the bed. Most
in some lesions affecting the motor neuron. When searching for infants are never able to sit without support when placed. Infants
fasciculation potentials, it is important to place the needle in the have weak sucking motions and difficulty swallowing, and poor
muscle and remove one's hand from the electrode for approxi clearing of secretions are quite common. Fasciculations are evi
mately 1 minute in order to observe for spontaneous activity. dent in the tongue. Interestingly, the muscles of facial expression
Documenting a MUAP, nonnal or abnonnal appearing, with an are relatively preserved initially but can become affected later.
irregular firing rate usually less than 3-5 Hz is suggestive of a Unfortunately, the intercostal muscles are also extremely weak
fasciculation potential. In chronic disorders, it is possible to ob and breathing primarily arises from the diaphragm. This results
serve complex repetitive discharges as characterized by their in paradoxic breathing (abdominal protrusion and costal reces
abrupt onset and cessation describing a constant morphology. All sion with inhalation). External ocular muscles and the sphincter
of the above abnonnalities should be found in a segmental as op muscles are usually spared; however, cases of facial diplegia and
posed to peripheral nerve pattern of abnonnality. Finding re ophthalmoplegia have been reported in infants with the charac
duced CMAP amplitudes, relatively nonnal motor conduction teristic mutation in the spinal motor neuron (SMN) gene (see
velocities, membrane instability in the fonn of positive sharp below).447 Sensation appears to be relatively well preserved, and
waves, and fibrillation potentials combined with nonnal SNAPs mentation is not compromised. There is typically complete ab
is certainly suggestive of motor neuron dysfunction. sence of all deep tendon reflexes. A fine tremor of the fingers can
588 - PART IV CLINICAL APPLICATIONS
Onset 6-18 months, variable survival--most survive into 2nd or 3rd decade
Autosomal dominant
Type 2
Juvenile-early adult onset of scapuloperoneal distribution weakness
Autosomal dominant with linkage to chromosome 12q24 (? Allelic to scapuloperoneal
motor neuropathy)
Type 3
Autosomal recessive
Type 4
Type 5
Juvenile onset
? Allelic to CMTlC
Usually with infantile onset (? Allelic variants with childhood or early adult onset)
Autosomal dominant
Linkage to chromosome 12q24 in some families (? Allelic with distal SMA type 2)
Type 2
Joiat COIItraclIIrel
mplratlry .Iran
parade.icII rlljliratloA
IIIp loin... knee joIIIlI
..
XII
.
Idegeneralion of crallal luCIei I
XI. X. IX
-+
VIII. VII. VI. IV. III
"
Figure 16-7. Diagrammatic flow of clinical symptoms and signs resulting from loss of anterior horn cells and cranial nuclei. Interestingly,
despite 10$$ of spinal ganglion cells. sensation remains well preserved in patienu. (From Osawa M. Shishikura K:Werdnig-Hoffmann disease and
varianu.lnVinken PJ, Bruyn Gw, Klawans HL (eds): Handbook of Clinical Neurology,Vol 59.Amsterdam. North Holland Publishing. 1991, pp 51-80,
with permission.)
be seen secondary to hand intrinsic fasciculations (polyminimy chromotolysis, swelling, and reduction in Nissl bodies. The
oelonus). Contractures are absent in most infants; however, a phrenic (C3-5) and sacral sphincter (S2-4) motor neurons are
mild limitation of shoulder external rotation, hip abduction, or usually spared with the typical degenerative changes correlating
knee extension can be detected in some patients. Further, cases with the observed clinical presentation. Commensurate with the
of arthrogryposis due to "infantile neuronal degeneration" are loss of anterior horn cells, the ventral spinal nerve roots are at
known to be caused by mutations in the SMN gene. 76 Unfor rophic with loss of large myelinated fibers. Of interest, there is
tunately 95% of patients expire by 18 months of age as a result also evidence to suggest at least some involvement of the sen
of pulmonary compromise. sory system with a loss of spinal ganglion cells and reported
Histopathology. The histopathologic findings are directly loss of sural nerve myelinated fibers. 257,513 Musele biopsy re
dependent on the pathophysiologic process involved in this dis veals severe groups of atrophic, rounded type I and 2 fibers in
ease (Fig. 16-8). Spinal cord and brain stem examination termixed with scattered large rounded fibers (usually type I
demonstrates profound degeneration of the anterior horn cells at fibers) (Fig. 16-9).121,442 Of note, the atrophic fibers are rounded
all levels with particularly severe changes noted in the lower in appearance in contrast to the angular appearance of dener
bulbar nuclei and cervicalllumbosacral cord enlargements.40I •603 vated muscle fibers that occur with onset later in childhood or
The motor neurons reveal the typical changes expected with adulthood. Occasionally biopsies demonstrate non-specific
590 - PART IV CLINICAL APPLICATIONS
~
skeletal .....scle
sis: Progression and survival in patients
neurogetlic ••sculll' atnlp., glial bundles with glu 100gly and ala4val mutations in
large 911111PS 01 .ull atropllic tibera
hypertrophic fibers
changes such as diffuse atrophy or fiber type disproportion sec demonstrate facial muscle weakness during the course of the dis
ondary to sampling error. In such cases, a repeat biopsy later in ease, Urinary and anal sphincters are preserved, as are the exter
the course may demonstrate the characteristic abnormalities. nal ocular muscles. Fasciculations of the tongue can be
However, with DNA testing now available, there is little indica observed, Fasciculations are not commonly observed in limb or
tion for performing muscle biopsies on these patients for diag axial skeletal muscles, but a tremor of the outstretched hand may
nostic purposes at the present time. be noted just as in SMA 1. Sensation remains intact in these pa
tients. Deep tendon reflexes are diminished or absent through
Autosomal Recessive Proximal SMA Type /I (Intermediate/Chronic out. Most affected children are intellectually normal.
Childhood Form of SMA) The long-term prognosis is considerably better than for SMA
Clinical Features. Patients with SMA II have a relatively I, with many patients surviving into the second or third decade
normal neonatal period and manifest signs between the ages of of life. A large prospective study demonstrated that some pa
6 and 18 months of life (Table 16_1).214,334,379,603,702,803,911,912 They tients with SMA II demonstrate relatively little progression over
are usually able to achieve motor milestones up to that age (e,g" several years suggesting that SMA II can be a stable disorder. 379
achieving the ability to sit unaided), although they have general Life expectancy is dependent on the degree of respiratory
ized hypotonia and weakness, Weakness is symmetric and af muscle preservation. If the lung function continues to be well
fects proximal greater than distal muscles. The legs are affected preserved, survival to adulthood is likely. The oldest patient in
more than the arms, and thus affected children typically are one large prospective study lived until the age of 72 yearsJ02
brought to medical attention secondary to the failure to stand Histopathology. The histopathologic findings in SMA II
and walk independently, However, assisted standing and ambu cannot be differentiated from those of SMA 1. 401
lation may be possible in some patients, About a third of patients
Autosomal Recessive Proximal SMA Type 11/
(Kugelberg-Welander Disease)
Clinical Features. SMA type III or Kugelberg-Welander
disease manifests after 18 months of age, usually between the
ages of 3 and 30 years (see Table 16-1 ).334.379,450,451,536,702,803,915,911.912
The symptoms of this disease are highly variable among indi
viduals. Affected patients appear quite normal until early child
hood or adulthood, at which point they usually develop an
insidious onset of proximal leg weakness and atrophy. With dis
ease progression, the shoulder girdle muscles also begin to de
crease in strength and patients have difficulty performing
overhead activities and activities of daily living dealing with
dressing and grooming. Some persons complain of painful
muscle cramps. A large prospective study demonstrated that
some patients with SMA III demonstrate relatively little pro
gression over several years, suggesting that SMA III can be a
stable disorder. 379
Examination demonstrates proximal greater than distal arm
Figure 16-9. Spinal muscular atrophy type I (Werdnig-Hoff and leg weakness and atrophy, The facial, masseter, and neck
man disease), Muscle biopsy reveals marked fascicular atrophy and muscles are often weak. A generalized reduction in muscle tone
scattered hypertrophic muscle fibers, is detected. Sensation is intact to all modalities. Deep tendon
Chapter 16 DISORDERSAFFECTING MOTOR NEURONS - 591
reflexes are diminished or absent. However, there can be rela The needle electromyographic examination is abnormal in all
tive preservation of the ankle reflex until late into the disease as forms of SMA.34.121,1 22.234.340.341.343 The disease severity and rate
sociated with hypertrophy of the calves. 87 Rare patients have of progression directly influence the degree of abnormalities de
been reported with hyperactive deep tendon reflexes and an ex tected. Because of lower motor neuron loss, there is a reduction
tensor plantar response, although these features have not been in the number of MUAPs during attempts at voluntary contrac
noted in genetically confirmed cases of SMA III to our knowl tion in all forms of SMA.27,282 The remaining MUAPs fire at
edge.282.578 rapid rates (i.e., demonstrate reduced recruitment).
Histopathology. Post-mortem examination of patients An alteration in the MUAP morphology may also be appreci
with SMA III disease demonstrates a profound reduction in ated. The loss of anterior horn cells combined with compen
anterior horn cells with no evidence of demyelination of the satory attempts at functional repair through collateral sprouting
spinal cord tracts. Some patients also have a degeneration of results in an increase in the number of muscle fibers per motor
the spinal ganglion cells with Wallerian degeneration of sen unit. This process creates MUAPs with increased amplitudes
sory nerve fibers.!31 Muscle biopsy demonstrates groups of and duration. An increase in mean MUAP amplitude and dura
atrophic, angular (rather than round) fibers and fiber-type tion may be detected in all forms of SMA, but this is seen the
grouping suggestive of chronic reinnervation. 5J9 Biopsy least in SMA I and more frequently with especially large
specimens of severely weak muscles may reveal end-stage MUAP amplitudes (10--15 m V) in SMA 111. 537 The latter disease
changes: marked fiber size variation, fiber splitting, degener is more commonly associated with significant motor unit re
ative or necrotic muscle fibers, and proliferation of intersti modeling because of its chronic nature combined with less pro
tial connective and fatty tissues that can be confused with found loss of anterior horn cells. The large magnitude of loss
muscular dystrophy.727 and rapid progression of SMA I does not permit large-scale
motor unit remodeling capable of generating 10--15 mV ampli
Molecular Genetics and Pathogenesis of SMA 1-111 tude MUAPs. Along with the increased amplitude and duration
These disorders as alluded to above are allelic and due to mu of MUAPs, an increase in the number of phases may also be ob
tations in the spinal motor neuron gene (SMN) located on served. Of interest, short-duration MUAPs can be observed in
chromosome 5q13.289.444.477.478.543.9Io There are two almost identi increased numbers compared with normals in SMA. Over time,
cal SMN genes, telemeric SMN (SMNt ) and centromeric SMN there is a preponderance of long-duration potentials particularly
(SMNc)' that differ by five nucleotides. Normal individuals con in SMA III; however, the short-duration MUAPs are still pre
tain two copies of SMN t and several copies of SMNc . SMA is sent.286.727 This so-called myopathic MUAP morphology may be
caused by mutations in both SMNt alleles. Approximately 98% directly related to the degenerative muscle fiber changes and
of the causes are associated with deletions, usually involving small-caliber fibers combined with an increase in fiber size vari
exons 7 and 8, while the other 2% are the result of conversion of ation noted on muscle biopsies. Occasional multiple discharges
the SMN t genes to the SMNc sequence. The age of onset and
severity of SMA may be modified by the number of intact copies
of SMNc and other neighboring genes.529.564,719 A single infant
with a SMA I-like phenotype and no mutation in the SMN gene
was demonstrated to have a mutation in the cytochrome c oxi
dase gene. 698
SMN is present in the cytoplasm of all cells and in nuclear
structures called "gems" that associate with nuclear coiled
bodies.494.524.905 These gems and coiled bodies are believed to
serve as storage sites for spliceosomes that excise introns from
newly synthesized small nuclear RNA (snRNA) to produce
messenger RNA (mRNA). However, prior to this splicing of the
snRNA into mRNA, SMN binds to and shuttles snRNA out of
the nucleus and into the cytoplasm, where it undergoes methy
lation to form mature small nuclear ribonucelic protein (snRNP)
or "snurps."626 SMN then shuttles the mature snRNP back into
the nucleus, where splicing to mRNA occurs, Thus, the funda
mental defect in SMA appears to involve abnormal trafficking
and splicing of RNA species.
(doublets/triplets) can be seen in SMA III.614 Quantitative needle fibrillation potentials and positive sharp waves are detected.
electromyographic techniques are necessary to properly evaluate With respect to positive sharp waves and fibrillation potentials,
the mean MUAP duration for at least 20 motor units and ampli the proximal compared with distal muscles tend to have higher
tude as well as count the number of polyphasic potentials prior numbers of these abnormal waveforms, as do the lower com
to concluding a myopathic disease process is operational. pared with upper limbs in SMA III, whereas SMA I patients
If a trigger and delay line are used, late potentials or so-called have a more diffuse pattern of abnormal potentials. 341 Complex
satellite potentials can be detected (Fig. 16-10).786 These poten repetitive discharges are typically encountered in SMA III,
tials can extend for rather long time periods beyond the main whereas they are relatively rare in SMA I. This is a result of the
MUAP complex. Additionally, some of the individual wave more chronic nature of SMA III permitting the formation of
forms comprising the entire potential may be unstable and fail ephaptically activated neighboring denervated muscle fibers.
to fire with each successive depolarization of the motor unit, Only about 20% of patients with SMA I have electrically de
Le., some fibers may block. The origin of these potentials may tectable fasciculation potentials, whereas about 60% of patients
be a result of outlier fibers from a denervated motor unit taken with SMA III have fasciculation potentials. 282 Some infants with
up by an intact neighboring motor unit through collateral SMA I have spontaneously discharging MUAPs firing at 5-15
sprouting. The instability with blocking most likely signifies a Hz even in muscle believed to be at rest (e.g., during sleep).344
tenuous or newly formed neuromuscular junction with a re Single-fiber electromyography demonstrated increased jitter
duced safety factor that fails to fire with each depolarization or and fiber density secondary to the formation of new terminal
ceases to function temporarily when a critical number of depo sprouts in the process of collateral sprouting (Fig. 16
larizations has been exceeded. 11).385.743.782.786 Macro-electromyography usually reveals a dra
A number of abnormal spontaneous potentials can be ob matic increase in MUAP amplitude at time reaching 25 times
served in the various types of SMA. Perhaps the most com the normal value, again secondary to collateral sprouting and an
monly observed abnormal potentials are positive sharp waves increased number of muscle fibers per motor unit. 784.786
and fibrillation potentials. These potentials are most frequent in
SMA 1. Essentially all patients with SMA I demonstrate wide Autosomal Recessive Proximal Spinal Muscular Atrophy Type IV
spread occurrences of both positive sharp waves and fibrillation This subtype of proximal SMA refers to patients with onset
potentials in all muscles examined, including the paraspinal of symptoms after the age of 30 years. The clinical, histologic,
muscles at multiple levels. 34o,442 In SMA III, however, only and electrophysiologic features are otherwise similar to those of
about 60% of patients have readily detectable fibrillation poten SMA IIJ.93,150,334,453.592.621.911,912 Mutations in the SMN gene have
tials and positive sharp waves that are more restricted in loca been detected in some of these patients, but not in others,911.912
tion, i.e., primarily the more severely affected muscles. This suggesting genetic heterogeneity of adult-onset autosomal re
reduction in the number of these potentials is a result of the cessive SMA.
slowly progressive nature of the primary disease process.
Specifically, when anterior hom cells are lost slowly, the com Autosomal Dominant Proximal Spinal Muscular Atrophy
pensatory process of collateral sprouting can keep pace with the Autosomal dominant SMA is much less common than the
denervation and provide an efficient mechanism of reinnerva above-described cases or autosomal recessive inheri
tion. If muscle fibers are quickly reinnervated because the re tance. I28•334,622,667 Onset can be at birth or middle adult life. It is
serve capacity of anterior hom cell is good, comparatively fewer estimated that less than 2% of childhood-onset cases but as
A B c o
~ 1_"
\~""4""""-
figure 16-1 '" Single fiber recordings from a patient with SMA type III. A,A single fiber pair demonstrating increased neuromuscular
jitter and blocking indicating a newly formed neuromuscular junction. B, The increased number of waveforms noted in this recording indicates an
increase in the number of muscle fibers innervated by a terminal nerve with an increase in jitter and some blocking defining newly incorporated
muscle fibers into the motor unit. e,A highly complex potential with stable early components but unstable later components defining both an in
crease in the number of innervated muscle fibers and jitter. D, This complex waveform is highly stable with normal jitter but elevated number of
innervated muscle fibers, suggesting the process is slowly progressive allowing mawration of the newly formed neuromuscular junctions. (From
Sdlberg E, Fawcett PRW: Electrophysiological methods for the swdy of the motor unit in spinal muscular atrophy. In Gamstorp I, Sarnat HB (eds):
Progressive Spinal Muscular Atrophies. New York, Raven Press, 1984, pp 111-134, with permission.)
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 593
many as 30% of adult-onset cases are inherited in an autosomal stem.5OS In addition, there is corresponding loss in the ventral
dominant pattern. Patients manifest with proximal leg greater motor roots. The corticospinal tracts are spared; however, pallor
than arm weakness. Facial weakness may be noted. Atrophy and may be noted in the posterior columns secondary to Wallerian
fasciculations are apparent in the limbs and tongue. Deep degeneration. In this regard, there is loss of dorsal root ganglia
tendon reflexes are reduced or absent. The childhood-onset cells. Sural nerve biopsy specimens often demonstrate a loss in
cases are usually relatively mild and slowly progressive. the number of myelinated nerve fibers, axonal atrophy, minimal
Children are able to ambulate, but wheelchairs may be required axonal sprouting and slight segmental demyelinationlremyeli
in some patients in their 30s. In contrast, adult-onset cases have nation. 23,36,331,508,868.886 Muscle biopsy samples reveal grouped at
more rapid progression of weakness and life expectancy may be rophy and fiber type grouping consistent with denervation as
diminished. Muscle biopsies and electrophysiologic studies are well as non-specific myopathic features (e.g., increased central
indistinguishable from the autosomal recessive forms of proxi nuclei, fiber splitting, hypertrophic fibers, and scattered necrotic
mal SMA. This autosomal dominant form of SMA does not link fibers).23,36.331.342,436
to chromosome 5q.429 Molecular Genetics and Pathogenesis. Kennedy's disease is
caused by a mutation in the androgen receptor gene on chromo
X-Unked Bulbospinol Muscular Atrophy (Kennedy's Disease) some Xq11-12.469 The mutation is characterized by an increased
Clinical Features. Kennedy's disease is an X-linked reces size of polymorphic tandem expanded CAG repeats within the
sive form of SMA characterized by adult onset of slowly pro first exon of the androgen receptor gene. The normal number of
gressive bulbar and proximal greater than distal limb weakness CAG repeats is 22 ± 3, while in patients with the disease the
and atrophy (Table 16-1 ).1S.23.33.36,48.257,331 ,342,344,43{;,5 12,546,574,600, number of repeats ranges from 39 to over 60. 381 ,469,470 The size of
668,738,768.790,868,886 Male patients usually have the disease manifest the repeats are mildly unstable during meiosis, such that they may
in the third to fifth decade, although some individuals are symp slightly expand or occasionally contract. There is greater instabil
tomatic as early as 15 years of age, while others are asympto ity during male meiosis compared with female meiosis. The rela
matic in the seventh decade of life. The onset of symptoms and tive stability of the size of the repeat probably accounts for the
the clinical severity correlate with the size of the genetic muta lack of significant anticipation phenomena appreciated in kin
tion (see below),381 although there is significant phenotypic vari ships with Kennedy's disease as opposed to other disorders with
ability between individuals with similar sizes of mutations. 23 expanded repeats (e.g., myotonic dystrophy, Huntington's dis
Patients can present with either proximal limb (usually legs ease, forms of spinocerebellar atrophy). The size of the repeat ap
greater than arms) or bulbar weakness (e.g., dysarthria or dys pears to correlate indirectly with the onset of symptoms (Le., the
phagia). Patients may note muscle atrophy, cramps, and fascicu larger the repeat, the earlier the onset).381,469,470.512 However, the
lations. In addition, observant patients may complain of breast repeat size has much less influence on the disease severity and
enlargement (gynecomastia), which usually manifests long other associated clinical features. 23•512
before the neuromuscular symptoms present. Despite the abnor The pathogenic basis for how the expanded CAG repeat in
mal sensory conduction studies (see below), patients do not de the androgen receptor gene leads to loss of lower motor neurons
scribe sensory loss, paresthesias, or neuropathic pain. The is not known. Androgen receptors are expressed in motor neu
disease is slowly progressive; however, many patients eventu rons as well as in muscle cells. The androgen receptor functions
ally become wheelchair-dependent and some patients may re as a transcription factor for other genes. The motor neuron loss
quire a gastrostomy tube secondary to severe dysphagia. associated with Kennedy's disease is thought to arise from a
Physical examination demonstrates a combination of prefer gain offunction of the androgen receptor rather than a loss of
entially proximal arm and leg weakness associated with cranial function caused by the mutation in the gene. The mutant gene
nerve dysfunction. The orbicularis oculi and oris muscle are product may increase the transcription of the target gene(s) or
often easy to overcome. Fasciculations may be apparent in the result in abnormal binding and regulation of transcription of
chin and other facial muscles at rest or following activation other genes. Aggregates of androgen receptors have been ob
(e.g., after puckering lips). Tongue atrophy and fasciculations served in motor nuclei in the brain stem and nuclei in patients
are also relatively common. The extraocular muscles are spared. with Kennedy's disease.
In the limbs, muscle weakness, atrophy, and fasciculations are Electrophysiologic Findings. Motor and sensory nerve con
pronounced about the shoulder and pelvic girdle regions. The duction studies and needle electromyography reveal character
muscle weakness can be asymmetric. There is relatively good istic abnormalities in patients with Kennedy's disease. 15,23,33,36,48.
preservation of the hand and foot intrinsic muscles until late in 331.253.342,436.546.574,600.668,738.790,868,886 The SNAPs are often reduced in
the disease. Mild sensory loss to all modalities can be demon amplitude or unobtainable in the arms and legs. There may be
strated in the distal arms and legs. A fine postural or action mild slowing of sensory conduction and prolonged distal laten
tremor in the hands can be noted in the majority of patients. cies proportional to the degree of axon loss. The sensory abnor
Deep tendon reflexes are usually depressed or absent, and plan malities occur in patients without diabetes mellitus; therefore,
tar responses are flexor. Gynecomastia and testicular atrophy this is not the cause of the sensory abnormalities. The involve
are frequently evident. Rare female carriers may manifest with ment of the sensory nerves in the arms at the same time or prior
bulbar signs (subtle tongue atrophy and fasciculations) or proxi to involvement of the legs suggests a sensory neuronopathy that
mal weakness.314.512 is reflected on autopsy findings of the dorsal root ganglia. The
Laboratory Features. Patients may have mildly elevated jaw jerk is often spared electrophysiologically as a result of the
serum CK levels. They can also demonstrate laboratory evi fact that the afferents for the mandibular reflex are within the
dence of androgen deficiency, and there may be an increased in central nervous system. 33
cidence of diabetes mellitus. Motor nerve conduction studies are characteristically normaL
Histopathology. Autopsy studies demonstrate a marked re The only abnormality occasionally noted is a reduction in
duction of anterior hom cells in the spinal cord and motor nuclei CMAP amplitude and in some patients a commensurate slight
of the trigeminal, facial, and hypoglossal nerves in the brain reduction in conduction velocity. Repetitive stimulation studies
594 - PART IV CLINICAL APPLICATIONS
are nannal, which may be of value in patients with initial bulbar atrophic anterior horn cells along with significant loss off neu
symptoms suggesting myasthenia gravis. rons in the spinal roots, cauda equina, and dorsal root ganglia. 808
Needle electromyography reveals a widespread reduction in Molecular Genetics and Pathogenesis. This disorder has
MUAP recruitment with MUAPs of large amplitude and long been linked to chromosome 3p14.1-q13 in one large kinship.80s
duration. Fasciculation potentials are prominent findings in The gene has not been identified. The similarity between
multiple limb and bulbar muscles. Diffuse fibrillation potentials HMSNP and Kennedy's disease, which is caused by mutations
and positive sharp waves are frequently detected in all muscles (expanded CAG repeats) in the androgen receptor gene on chro
examined. Single-fiber electromyography demonstrates in mosome Xq21, suggests that a similar pathogenic mechanism
creased fiber density, jitter, and blocking. 1s may be involved.
Although female carriers usually do not manifest clinical Electrophysiologic Findings. Electrodiagnostic abnonnali
symptoms, occasional electrophysiologic abnonnalities have ties similar to those of Kennedy's disease are appreci
been documented. 314,512,546,768 Decreased amplitudes of SNAPs ated.203.38(),383,611.721,808 SNAP amplitUdes may be normal or
were found in 3 of 14 female carries in one study.512 In this reduced, while the distal latencies are normal. CMAP ampli
cohort, 8114 patients had increased amplitude MUAPs on EMG. tudes are moderately decreased, whereas conduction velocities
However, fibrillation potentials were described in the tibialis an are nonnal or only mildly diminished. Distal motor latencies are
terior muscle in only one patient and the orbicularis oculi in two preserved. Electromyography reveals diffuse fasciculation and
patients. No mention was made of the presence or absence of fibrillation potentials. Long-duration polyphasic MUAPs with
fasciculation potentials, the duration and phases of the MUAPs, decreased recruitment are also evident.
or their recruitment. Other studies have also commented on rare
decreased SNAP amplitudes or high-amplitude MUAPs in Distal Spinal Muscular Atrophy
female carriers. 314,512,546,76S Clinical Features. This is a clinically and genetically het
Treatment. There is no proven therapy to improve strength erogeneous group of disorders associated with distal limb weak
and function in patients with Kennedy's disease. Testosterone or ness and atrophy (Table 16-1 ).4,91,313,330,334.420,533.538,604.623 Some
anabolic steroids may improve muscle strength, but it is un patients have their disease manifest predominantly in the hands,
likely that this is a direct effect as the androgen receptor muta while others present with distal lower limb weakness. Further,
tion causes a gain of function of the receptor (e.g., the motor the disorders can be inherited in either an autosomal dominant
neuron cell loss is not a result of a reduced androgen effect). or recessive fashion. Onset is usually in the first or second
Physical, occupational, and speech therapy is helpful. Patients decade of life. There is some overlap between cases reported as
may require a gastrostomy tube, if their dysphagia becomes scapuloperoneal neuropathy (see below), fonns of CMT (i.e.,
severe. CMT2C and CMT2D), and different types of distal SMA.
Some individuals manifest with distal lower limb weakness.
Autosomal Dominant Bulbospinal Muscular Atrophy The anterior tibial compartment is more affected than the pos
Clinical Features. This disorder resembles Kennedy's dis terior compartment. Thus, patients often manifest with foot
ease except for the autosomal dominant inheritance and is proba drop. The disorder is rather slowly progressive and may involve
bly the same disorder as so-called proximal hereditary and some degree of muscle wasting in the hip girdle musculature.
sensory neuropatby/neuronopathy (HMSNP).203·380·383.611.721.808 Over time, the hand intrinsic, foreann muscles (extensors >
Patients usually develop proximal muscle atrophy and weak flexors), and triceps are often affected. Some of the reported
ness, legs worse than arms, after the age of 20 years (mean 45 ± cases clinically resemble what others have called scapuloper
6 years). Mild facial weakness is also present, but neck flexors oneal neuropathy.
and extensors are relatively spared. The disorder is slowly pro The second major fonn of clinical presentation is that of bi
gressive, and patients usually become nonambulatory 5-20 lateral weakness and atrophy of the hand intrinsic muscles.
years after symptom onset. Widespread fasciculations are evi Occasionally the forearm muscles, primarily but not exclusively
dent in the trunk and limbs. Dysarthria and a nasal quality to the flexor muscles, can become affected. There is little or no pro
speech may be appreciated. While mild atrophy and fascicula gression of the muscle wasting to the shoulder girdle or lower
tions are noted in the tongue, significant dysphagia is uncom limb regions.
mon. However, some patients will require tracheostomy and Physical examination demonstrates the above-noted patterns
mechanical ventilation as a result of bulbar and respiratory of muscle atrophy and weakness. A few persons do demonstrate
muscle weakness late in the course of the disease. As with significant hypertrophy of the gastrocnemius and soleus mus
Kennedy's disease, reflexes are diminished or absent, a neuro cles bilaterally.313 Pes cavus defonnities are common. Affected
genic tremor is common, and there is an association with type 2 infants may be born with arthrogryposis. 4 Some patients have
diabetes mellitus. Mild dysesthesias are present in the distal scoliosis. Sensation is completely nonnal in both the upper and
limbs. Muscle cramps are common. Sensory examination re lower limbs. One third of patients have absent ankle jerks, but
veals decreased vibratory and position sensation and, to a lesser knee and upper limb reflexes are preserved in approximately
extent diminished pain, temperature, and touch. Further, gy 80% of patients. 330 Plantar reflexes are commonly flexor; how
necomastia may be appreciated in affected males. ever, a few patients have been reported with all of the above
Laboratory Features. Serum CK is often mildly elevated. characteristic symptoms and physical findings along with ex
In addition, type 2 diabetes and hyperlipidemia may be seen. tensor plantar responses. I48a,846 These individuals may represent
Histopathology. Sural and posterior tibial nerve biopsy may fonns of hereditary spastic paraparesis that are associated with
demonstrate a loss of large and small myelinated nerve fibers concurrent distal SMA.
with preservation of unmyelinated nerve fibers. 8°S Teased nerve CMT2C is an autosomal dominant axonal fonn of CMT,
fiber preparations reveal active axonal degeneration. There is no which is clinically and genetically distinct from CMT2A and
evidence of demyelination. Muscle biopsies reveal neurogenic CMT 2B.219.544,648,904 The distinguishing feature is the occurrence
atrophy. Autopsy on one patient showed only a few remaining of vocal cord paralysis in CMT2C. The age of onset is variable,
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 595
and symptoms can begin in infancy. Infants can manifest with compared with distally. Of note, persons with distal spinal
breathing difficulties and stridor. More common is the insidious muscular atrophy may have a high incidence of carpal tunnel
onset of laryngeal weakness causing progressive hoarseness. In syndrome. 604 •846 In these individuals, the motor and sensory
addition. the diaphragm and intercostal muscles are often weak, distal latencies as well as sensory amplitudes are commensurate
leading to reduced respiratory function. Some patients will re with those anticipated for a median nerve entrapment neuropa
quire tracheostomy and mechanical ventilation. Atrophy of the thy at the wrist. Recall that a reduction in muscle bulk can lead
distal limbs is common, and patients can develop proximal and to a reduced limb temperature, and this parameter must be care
distal weakness of the arms and legs. There is mild sensory loss fully controlled when performiog both sensory and motor nerve
to all modalities, and deep tendon reflexes are reduced. Pes conduction studies.
cavus can be appreciated in some patients, but such foot defor The motor nerve conduction studies may demonstrate re
mities are not as common as seen in CMT1, CMT2A. or duced CMAP amplitudes in affected muscles. 4.90.9I ,313,330,533.623
CMT2B. Similar cases have reported in the literature as heredi The distal motor latencies and conduction velocities in both the
tary distal spinal muscular atrophy with vocal cord paraly upper and lower limbs are usually normal. The major exception
sis. 648•904 However. the presence of sensory nerve abnormalities would be that noted above for the median nerve when carpal
favors the inclusion of this disorder into the CMT category tunnel syndrome is present.
rather than as a subtype of spinal muscular atrophy.219,544 Needle electromyography reveals a reduced MUAP recruit
Distal SMA type 5 and CMT2D appear to be allelic disor ment in the affected musc1es. 4 ,90.9I,313.330,533.623 The remaining
ders co-localizing to chromosome 7p15,23J,712 CMT2D is an MUAPs are polyphasic and increased in amplitude and dura
other autosomal dominant form of CMT2, which is clinically tion. Positive sharp waves and fibrillation potentials may be ob
and genetically distinct from CMT2A, CMT2B, and CMT2C. served; however, these are not usually prominent. In particular,
Onset of the disease is usually in the late teens (range between the paraspinal muscles often lack abnormal spontaneous activ
the ages of 12 and 36 years), and the neuropathy has a slowly ity.420 This lack of florid membrane instability despite signifi
progressive course,379,712 Weakness and atrophy of the hands are cant muscle wasting is consistent with the slowly progressive
more severe than that in the distal legs, Distal hypesthesia to all nature of the disease permitting significant collateral sprouting
sensory modalities may be noted, Deep tendon reflexes are gen and hence motor unit remodeling (MUAP amplitude and dura
erally absent in the arms and reduced in the legs. Pes cavus, tion alterations). Fasciculation potentials can be observed in
hammertoes, and scoliosis are variably present. Enlarged palpa some persons. 313 A single person has been reported with contin
ble nerves are not appreciated. uous motor unit activity in the affected muscles. l36
Histopathology. Muscle biopsies demonstrate features of
chronic neurogenic atrophy.91.313 Sensory nerve biopsies are Progressive Bulbar Paralysis of Childhood
usually normal. 4 However, electron microscopy has demon Clinical Features. Progressive bulbar paralysis of childhood,
strated axonal pathology in sensory nerve biopsy specimens that also known as Fazio-Londe disease, is a very rare disor
by routine semithin sections and teased fiber analysis appeared der. I 8.63,I87.300,301.334 These patients have an uneventful delivery and
normalPI This supports the impression that there may be some initial development. Withio the first 5 years of life, usually prior to
overlap between subtypes of CMT2 and distal SMA. the age of 2 years, patients develop inspiratory stridor and a hoarse
Molecular Genetics and Pathogenesis. This is a clinically voice. Laryngoscopy reveals paretic vocal cords. Additionally,
and genetically heterogeneic group of disorders (Table 16-1). there is progressive loss of facial expression along with variable
Some kinships have autosomal dominant inheritance, while auto degrees of ptosis, masseter and temporalis muscle weakness, and
somal recessive inheritance is seen in other families. Cbromo limited abduction weakness of the eyes. The sternocleidomastoid
somal linkage has been established io a few kinships, but the exact muscle may appear weak and atrophic. Atrophy and fasciculations
genes have not as yet been identified.393 Linkage to chromosome may be observed io the tongue musculature. The patient may have
12q24 was established in one kinship with distal motor neuropa mild hypotonia or normal muscle tone. Deep tendon reflexes may
thy (SMA) type 2. Of note, this same region links to scapuloper be normal or slightly brisk, and plantar responses are flexor.
oneal SMA; therefore. they may be allelic disorders. So-called Sensation is normal throughout, iocludiog the face. A few patients
distal SMA type 5 characterized by bilateral hand weakness and demonstrate intention tremor of the upper limbs. Unfortunately,
atrophy of the thenar eminence is linked to chrOmosome 7p14-l5 most patients expire of pulmonary complications withio 2 years of
and appears to be allelic with CMf2D.231.712 Some forms of auto the clinical presentation of laryngeal stridor.
somal dominant distal SMA with hand iovolvement are also asso llistopatbology. Autopsies reveal degeneration of!8. 187,300,30I,334
ciated with hoarseness as a result of degrees of vocal cord cranial nerve motor nuclei m, IV; V, VI, VII, X, and XII. A loss
paralysis and respiratory compromise secondary to diaphragmatic of anterior hom cells in the upper cervical segments is evident;
iovolvement. 648•904 Autosomal recessive distal SMA with diaphrag however, the remainder of the spinal cord appears normal.
matic paralysis links to chromosome 11q 13-q21. One kinship with Laryngeal and cervical strap muscles demonstrate microscopic
autosomal recessive distal SMA with features of superimposed evidence compatible with profound denervation.
spastic paraparesis linked to chromosome 9p21.1-12.1 48a Molecular Genetics and Pathogenesis. The pathogenic
Electrophysiologic Findings. Sensory nerve conduction basis of the motor neuropathy is unknown.
studies are characteristically normal in the upper and lower Electrophysiologic Findings. The motor and sensory nerve
limbs with respect to all parameters: conduction velocity, am conduction studies of the limbs are normal. Stimulation of the
plitude, and distal sensory latency.4.90.91.313.330.533.623 The lack of facial nerve usually reveals a completely absent CMAP. The
abnormal sensory findings on clinical examination and on nerve needle electromyographic examination of the upper and lower
conduction studies helps to distinguish distal SMA from CMT limbs revealed only positive sharp waves and fibrillation poten
2, which it can otherwise resemble. A few patients have been re tials in a single patient, while the remaining patient examined
ported to have some degree of increased temporal dispersion re demonstrated no limb electromyographic abnormalities. Needle
garding the SNAP when the nerve is excited proximally electromyographic examination of the bulbar muscles can
596 - PART IV CLINICAL APPLICATIONS
demonstrate positive sharp waves and fibrillation potentials variant of myofibrillar myopathy). The similar clinical presenta
with reduced MUAP recruitment. tions of the above disorders result in considerable confusion in
the literature. Only when the specific gene loci are identified for
Progressive Bulbar Palsy with Deafness each of the above clinical syndromes will a better understanding
(Brown-Vialett~van Laere Syndrome) of these disorders be achieved.
Clinical Features. This rare autosomal recessive disorder is The onset of symptoms usually begins insidiously at about
characterized by the initial onset of deafness (vestibular and the second or third decade of life. Patients usually note diffi
cochlear nuclei affected) usually in the first decade of life culty involving the legs with recurrent ankle sprains, or tripping
(range 1.5-31 years) with subsequent development of facial especially during running activities. Over the course of the en
weakness, dysphagia, and dysarthria. 13 .277 •672,798 Patients may not suing several years, there is increasing trouble arising from low
only be deaf, but also experience difficulty ambulating sec chairs. At some point following the ambulatory difficulty, pa
ondary to vestibular dysfunction. This disorder is slowly pro tients note a reduced ability to perform activities requiring over
gressive, and the upper and lower limbs may become atrophic head activities. Examination reveals muscle wasting about the
and weak over many years. Sensory examination is typically shoulder girdle (pectoralis, serratus anterior, rhomboids,
normal. Initially the deep tendon reflexes can be mildly in supraspinatus, infraspinatus, trapezius, deltoid, and brachioradi
creased, but they become depressed over time. A few patients alis) muscles as well as the anterior compartment (peroneal in
can have extensor plantar responses. Patients may also have ev nervated) muscles of the legs. Ptosis and restriction of external
idence of optic nerve atrophy, retinitis pigmentosa, and cerebel ocular movements are uncommonly noted. The muscles of
lar ataxia. 416 facial expression are normal or only mildly weak, as are the
Histopathology. Pathologic examination of the brain stem sternocleidomastoid muscles; however, the remaining cranial
and spinal cord demonstrates significant loss of cranial nerve nerve musculature is spared. Hip flexion and abduction, knee
nuclei, particularly of the eighth nerve and anterior hom cells. extension, as well as ankle plantar flexion are mildly reduced.
Molecular Genetics and Pathogenesis. The pathogenic Of note, the extensor digitorum brevis and hand intrinsic mus
basis of this disorder is unknown. cles are well preserved. The unusual muscle distribution of
Electrophysiologic Findings. The sensory nerve conduction proximal upper and distal lower limb muscles is the clinical dis
studies are typically normal in both the upper and lower limbs. tinguishing characteristic of the scapuloperoneal syndromes.
A few patients can have some degree of mild reduction in SNAP Sensation to all modalities are normal. Pes cavus is evident in
amplitude and conduction velocity; however, the bulbar paraly some patients. Deep tendon reflexes are well preserved in most
sis renders nutritional intake inadequate, and a mild nutrition patients but may be reduced in advanced disease, and the plan
ally based peripheral neuropathy may account for these tar responses are flexor.
findings. Motor nerve conduction velocity is characteristically Histopathology. Muscle biopsy demonstrates small angu
normal, as is the distal motor latencies; however, the CMAP lated fibers, grouped atrophy, and fiber type grouping suggest
may be reduced in severely affected cranial or limb muscles. Of ing a primary neurogenic as opposed to myogenic process.
note, H-reflexes may be detected with ease in muscles not com Sural and superficial peroneal nerve biopsies are essentially
monly yielding this response, e.g., hand intrinsic muscles. Also, normal, confirming the lack of sensory abnormalities clinically.
F-waves can be rather large. The latencies for both of these re Autopsies have demonstrated degeneration of the anterior hom
sponses is normal. cells.
Needle electromyographic examination demonstrates a pro Molecular Genetics and Pathogenesis. The pathogenic
found reduction in MUAP recruitment in cranial innervated basis for the different forms of scapulperoneal motor neuropa
muscles. There is also a variable degree of MUAP recruitment thy or SMA is not known. An autosomal dominant family with
in limb muscles depending upon the severity of the disease scapuloperoneal SMA has been linked to chromosome 12q24.1
process. Large-amplitude long-duration polyphasic MUAPs are q24.31, but the gene has not been identified. 393
characteristically documented in both the cranial and limb mus Electrophysiologic Findings. In patients with scapuloper
culature. Positive sharp waves and fibrillation potentials are oneal SMA, the nerve conduction studies are relatively normal. 813
commonly observed in both the bulbar and limb muscles. Upper and lower limb sensory studies demonstrate normal ampli
Fasciculation potentials are only rarely detected, and single tude SNAPs as well as normal distal sensory latencies and con
fiber electromyography demonstrates an elevated fiber density duction velocities. Motor nerve conduction studies have normal
as well as increased jitter and blocking in the limb musculature. distal motor latencies and nerve conduction velocities. Peroneal
CMAP amplitudes may be reduced, but otherwise motor conduc
Scapuloperoneal Spinal Muscular Atrophy tion studies, incl~ding distal latencies and conduction velocities,
Clinical Features. Scapuloperoneal SMA is an extremely are normal.
rare disorder with reported sporadic, autosomal dominant and The needle electromyographic examination can reveal a
recessive, as well as possible X-linked forms of occurrence number of interesting findings, some of which can be quite con
(Table 16_1).237.246.4 15.416.527.545.569.665.807.813 This type of SMA is one fusing depending upon when it is performed during the patient's
of several forms of muscle weakness presenting in the scapu disease course.237.415.545,569,665,807,813 The MUAP recruitment can
loperoneal distribution of both a neurogenic and myopathic be primarily neurogenic (reduced numbers of large-amplitude
origin constituting the so-called scapuloperoneal syndromes long-duration MUAPs firing at rapid rates) or mixed (a combi
(see Chapter 27, Hereditary Myopathies): (1) scapuloperoneal nation of large-amplitude long-duration, and small-amplitude
muscular dystrophy (autosomal dominant); (2) scapuloperoneal short-duration MUAPs). Although large numbers of serial quan
spinal muscular atrophy (primarily autosomal dominant); (3) titative needle electromyographic studies have not been per
autosomal dominant neuropathic scapuloperoneal syndrome formed, there is a suggestion that different muscles in the same
with distal sensory symptoms (Davidenkow syndrome); and (4) patient can display both patterns of abnormality as well as
scapuloperoneal amyotrophy with cardiomyopathy (possible change from one to the other over time. This "impression" from
Chapter 16 DISORDERSAFFECTING MOTOR NEURONS - 597
distal motor latencies are usually normal, but may demonstrate HSP are being reclassified into various spastic paraplegia
mild slowing proportionate to the degree of axon loss. . groups (SPG) (Table 16-2).The prevalence ofHSP ranges from
The needle electromyograpnic examination is abnormal in 2.0 to 4.3 per 100,000. 530 Harding classified patients into "pure
the affected arm(s).158.194.338,358.359.643,644,769.814 The most frequently HSP," if there was only spasticity and sensory involvement; and
observed abnormality is increased amplitude and duration of the "complicated IISP,'' if there was associated optic atrophy, deaf
MUAPs in the affected muscles as well as reduced recruitment. ness, extrapyramidal disease, dementia, ataxia, peripheral neu
This pattern may be detected in more proximal muscles not ropathy, amyotrophy, or epilepsy.330 Patients are classified on
clinically observed to be wasted or weak. The contralateral the basis of age of onset: type 1, with onset before 35 years; and
limb, even when seemingly unaffected, may be abnormal in type 2, with onset greater than 35 years. With advances in ge
30-90% of patients. This finding documents that a large per netics, this classification scheme has been found to be less than
centage of patients with Hirayama's disease have bilateral but ideal because there is significant clinical and genetic hetero
asymmetric disease. Fibrillation potentials and positive sharp geneity between and within kinships with HSp'530
waves can be detected early in the disease course, but are less Physical examination reveals spastic tone in the legs with hy
common after the disorder has stabilized for a few years. Rarely, perreflexia and extensor plantar responses. The manual muscle
complex repetitive discharges are noted in the compromised test may be difficult to assess secondary to the increased tone;
limb. Examination of the lower limbs fails to demonstrate any however, weakness can be occasionally demonstrated in the
abnormalities. Single-fiber electromyography reveals increased legs. Muscle wasting and associated intrinsic minus (pes cavus)
jitter and fiber density in the affected muscles. Also, an elevated feet are commonly noted. The upper limbs are usually normal,
fiber density can be found in the clinically unaffected muscles although a few patients may have slightly increased reflexes.
on the contralateral side. However, some families with HSP have significant wasting of
the hand intrinsic muscles.7S3 Sensory loss is evident in 10-60%
Other Hereditary Multisystem Disorders of patients with "pure HSP" (more prevalent with long-standing
Affecting Motor Neurons disease) and usually involves large fiber modalities (e.g., vibra
Hereditary Spastic Paraplegia tory perception).S30 The sensory loss is believed to reflect cen
Clinical Features. The hereditary spastic paraplegias (HSP) tral rather than peripheral nerve involvement. However, sensory
are a clinically and heterogeneous group of disorders character loss can occur secondary to peripheral neuropathy in compli
ized by progressive lower limb spasticity.149,16S.284,534.624 This cated HSP. Cranial nerves are usually intact. Urinary hesitancy,
group of disorders has been subclassified by the pattern of in frequency, urgency, and incontinence develop in up to 50% of
heritance, age of onset, and the presence of additional neuro patients. S30 Rectal dysfunction is uncommon. The disease is
logic defects. s30 The disorder may be inherited in an autosomal only slowly progressive, and life expectancy is not affected. A
dominant, autosomal recessive, or X-linked nature. As linkage few patients may continue to ambulate throughout their life,
to specific chromosomes and genes have been described, the suggesting only a mild degree of disease progression.
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 599
Laboratory Features. CSF is usually normal, although in An X-linked form of HSP (SGP2) is caused by mutations in
creased protein is noted in some patients. 530 MRI scans may the proteolipid protein gene (PLP).485 Mutations in the PLP
demonstrate atrophy of the spinal cords and occasionally the gene are responsible for the CNS dysmyelinating disorder
cerebral cortex. 53O Some forms of HSP (SPOl) are associated Pelizaeus-Merzbacher disease. It is now known that PLP is also
with atrophy or agenesis of the corpus callosum.410.851 present on CNS and PNS myelin, and patients with mutations
Histopathology. Autopsy studies demonstrate the loss of affecting this gene can present with HSP associated with a de
axons in the ventral and lateral corticospinal tracts.530.814 A gen myelinating peripheral neuropathy. An additional type of com
eral reduction in the total number of myelinated fibers in the plicated X-linked HSP (SPOl) is associated with infantile onset
dorsal columns and peripheral nerves may be noted. Further, HSP, severe mental retardation. congenital musculoskeletal ab
neuronal degeneration may be appreciated in the cerebral normalities, agenesis of the corpus callosum, and hydro
cortex, basal ganglia, and brain stem in patients with compli cephalus.53O SPOI is caused by mutations in the gene encoding
cated HSP. Lewy and tau immunoreactive neurofibrillary tan for the Ll cell adhesion molecule (Ll CAM).41O.857 L 1CAM is a
gles have been described in autopsies of patients with mutation transmembrane glycoprotein that is expressed by neurons in
in the spas tin gene. 874 Schwann cells and is thought to playa role in the development
Molecular Genetics and Pathogenesis. This is a geneti of the CNS, particularly in regard to neuronal outgrowth and
cally heterogeneic group of disorders (Table 16-2). As noted pathfinding.53O
above, the disorder may be inherited in an autosomal dominant, Electrophysiologic Findings. There are very few detailed
autosomal recessive, or X-linked fashion. Autosomal dominant reports describing the electrophysiologic features of HSP. In
inheritance accounts for approximately 70% of pure HSP. Most some kinships with pure HSP, motor and sensory nerve conduc
of these autosomal dominant families are linked to mutations in tion studies are normaL534 However, in complicated HSP associ
the spastin gene located on chromosome 2p22-p21 (SOP4).874 ated with peripheral neuropathies, the nerve conduction studies
Spastin appears to be a nuclear protein with ATPase activity. are abnormal. 149 Mild reductions in motor and sensory nerve
Spastin is thought to playa role in cell cycle regulation, protein conduction velocities may be observed.485 Somatosensory
degradation, organelle biogenesis, and vesicle-mediated protein evoked potentials may be absent or delayed in the upper and
function. 530 Other autosomal dominant forms of HSP have been lower limbs suggestive of central conduction slowing.624.627
linked to various chromosomes, but the genes have yet to be Motor conduction along central pathways may also be
identified (Table 16-2).530 SIOW. 624•640 The needle electromyographic examination may
An autosomal recessive HSP (SP07) has been linked to mu demonstrate abnormal insertional activity (e.g., fibrillation and
tations in the gene encoding for paraplegin.132 Paraplegin is a fasciculation potentials), and the MUAPs can demonstrate in
nuclear-encoded mitochondrial metalloproteinase, and muta creased amplitude and duration.
tions in the gene result in impaired oxidative phosphorylation.
Another autosomal recessive form of HSP (also known as Hexosaminidase Deficiency (GM2 Gangliosidosis)
Sjogren-Larsson syndrome) is caused by mutations in the gene ClinicaJ Features. Hexosaminidase is a lysosomal enzyme
encoding for fatty aJdehyde dehydrogenase. '86 Other autoso that metabolizes highly polar lipids such as OMTganglioside
mal recessive forms of HSP have yet to be linked to various and other glycosphingolipids,134.405.695.697.819.836 The enzyme hex
genes (Table 16-2).530 osaminidase is comprised of two different subunits, a and 13,
600 - PART IV CLlNJCALAPPLlCATJONS
under the direction of specific gene loci on chromosome 15 and expected in a disease preferentially affecting motor neurons. m
5. respectively. There are at least three isoenzyme forms known Needle electromyography demonstrates fasciculation potentials,
with a well-delineated subunit composition: hexosaminidase A positive sharp waves, and fibrillation potentials. A reduced re
(a~)n, hexosaminidase B (~~)n, and hexosaminidase S(aa)n. cruitment of large-amplitude long-duration MUAPs is noted in
Hexosaminidase A in particular is required to metabolize GM r the affected muscles.
ganglioside that is believed to be bound to a protein activator
forming a complete substrate for the enzyme. Defects in the Multiple System Atrophy (Shy-Drager Syndrome)
protein activator or the subunits noted above can lead to the ac Clinical Features. Multiple system atrophy, commonly re
cumulation of the lipid materials in various tissues such as neu ferred to as Shy-Drager syndrome, is a multisystem degenerative
rons, thus producing individual lipid storage diseases with disorder of the CNS with associated features of parkinsonism
different phenotypic characteristics classified according to the and autonomic nervous system failure. 44.5o.78o The male-to
phenotype, gene locus, and allele affected. These disorders are female ratio is approximately 3: 1. The onset is usually in the
usually inherited in an autosomal recessive manner. Perhaps the sixth decade with a range of 37-75 years. A primary manifesta
best known diseases belonging to this biochemical disease cate tion of this disease is profound orthostatic hypotension that is
gory are those with cherry-red spots and infantile en progressive in nature. Initially, patients may complain only of
cephalopathies: Tay-Sachs disease (homozygous HEXa 2 mild dizziness, post-exertional weakness, dimness of vision, or
allele: therefore, absence of hexosaminidase A and S), unsteady gait particularly after physical exertion. Men often
SandhotT disease (homozygous for HEX~2 allele), and the AB note an impaired libido and impotence associated with the or
variant (deficiency of the hexosaminidase A activator protein). thostatic hypotension as an initial disease presentation. These
In these diseases, infants are quite normal until approximately symptoms progress over the course of several years to possibly
4-6 months of age except for a myoclonic jerk to loud sounds render some patients completely nonfunctional and restrieted to
and a macular cherry-red spot. They then become hypotonic and bed. Occasionally, an abrupt onset of these symptoms may be
weak with hyperreflexia, clonus, and extensor plantar re noted. Impaired sweating and poor temperature control render
sponses. By the end of the second year of life, the patients are the patient heat-intolerant. Urinary and fecal incontinence also
blind and in a vegetative state, eventually becoming decorticate becomes a significant limiting factor. In a study of this disease,
with death occurring by the sixth year, usually of some type of the following autonomic difficulties and frequency of occur
infectious process to the lung. This disease is particularly rence were noted: postural hypotension (95%), urinary dysfunc
common in persons with an Ashkenazi Jewish background. tion (65%), bowel incontinence or constipation (51 %), reduced
Neurons throughout the nervous system are grossly distorted libido or impotence (30%), and reduced ability to sweat
and filled with lipid material. Other phenotypes of the hex (11%).817 A number of somatic disturbances are also commonly
osaminidase deficiency can occur and include late-infantile or involved: gait disturbance (39%), difficulty with speech (28%),
juvenile encephalopathy (juvenile Tay-Sachs or Sandhoff dis tremor (26%), limb clumsiness (19%), handwriting difficulty
ease), juvenile or adult-onset cerebellar ataxia, adult-onset en (18%), distal limb sensory complaints and reduced sensation
cephalopathy, and a motor neuron disease type of presentation. (14%), and trouble swallowing (12%).
It is the involvement of motor neurons that is of interest in On physical examination, findings can be related to those
this chapter. The patient's parents may be of Ashkenazi origin. portions of the nervous system most commonly involved. 50 The
Patients may have a disease onset in childhood, adolescence, or corrico-bulbar and corrico-spinal abnormalities consist of gen
adulthood with a clinical presentation resembling SMA II or eralized hyperreflexia, extensor plantar responses, dysarthria,
II1.406 For example, a patient in the second or third decade may and a sucking reflex. Basal ganglia dysfunction is manifested as
present to a physician because of increasing difficulty walking masked facies, limb rigidity with or without cogwheeling, voice
with the presence of some lower limb deficits of a minor degree with a monotone quality, and resting tremor. Signs of cerebellar
for the past) 0 years. Difficulty running, jumping, and arising difficulty include intention tremor, gait ataxia, and dysarthric
from low chairs may have been present for some time. Muscle speech. Distal limb muscle wasting and fasciculations as well as
strength in the lower limbs is diminished throughout with some lax rectal tone may be detected in 59% and 71 % of patients, re
what better preservation distally. Cramps affecting the large spectively. The disease has a relentless course with progression
lower limb muscle groups may also have been present for years. of all of the above-noted symptoms and signs. By the time so
Upper limbs are relatively normal, and the only cranial nerve matic neurologic problems manifest, significant autonomic dis
abnormality is some suggestion of fasciculations. Widespread turbances have been present for quite some time. Death usually
fasciculations are noted in both the bilateral upper and lower ensues from some form of pulmonary compromise on average
limb musculature. There is usually no sensory impairment. by 7-8 years after symptoms onset, with some persons surviv
Deep tendon reflexes in the upper limbs are normal, whereas ing to 20 or 30 years.
the lower limb reflexes are decreased at the knees and absent at Histopathology. Autopsy studies demonstrate neuronal de
the ankles. Plantar responses are flexor, and pes cavus is present generation throughout the eNS. The intermediolateral cell
but without scoliosis. Intellectual function is normal. column of the spinal cord is especially affected, with up to 85%
Laboratory assay reveals a profound hexosaminidase A defi of cells no longer identifiable. The following structures can also
ciency. Autopsy studies reveal lipid accumulation in neurons of demonstrate cell loss: cerebellum's Purkinje layer, corpus stria
the cerebral cortex, anterior horn cells, autonomic ganglia, and tum, substantia nigra, vagus' dorsal motor nucleus, locus
rectal mucosa. ceruleus, spinal cord's anterior hom cells, pontine nuclei, and
Electrophysiologic Findings. Sensory and motor nerve con olivopontocerebellar tracts. The sural nerve biopsy reveals loss
duction velocities are usually normal. 406 •716 The only exception of the myelinated and unmyelinated fibers.
may be a reduced CMAP amplitude when recorded from mus Electrophysiologic Findings. There have been very few
cles with significant wasting. Median and tibial nerve so electrodiagnostic medicine reports in the literature describing
matosensory evoked potentials are also normal, as would be the findings in patients with multiple system atrophy. A few
Chapter 16 DISORDERSAFFECTING MOTOR NEURONS - 601
patients have had completely normal nerve conduction and LMN); and (4) amyotrophic lateral sclerosis (a variable com
needle electro myographic studies. 145 The sympathetic skin re bination of all of the preceding abnormalities, i.e., both UMN
sponse is likely to be absent. 902 and LMN signs affecting both the bulbar and somatic muscula
Some individuals have had normal motor nerve conduction ture).116.142,229,517.590,838,891 Individuals with progressive muscular
studies combined with needle electromyographic documenta atrophy (PMA) account for roughly 10% of all patients with
tion of reduced MUAP recruitment of both normal- and large motor neuron disease. 332,345,590,592.621,667,803,828.887 Primary lateral
amplitude long-duration polyphasic MUAPs.145.308.377,745 These sclerosis (PLS) likewise makes up at most only 1-3% of motor
persons may have electrophysiologic findings suggestive of neuron disease cases. 345 ,649.804,828,906 Progressive bulbar palsy ac
motor neuron disease. Combining the normal motor conduction counts for approximating 1-2% of motor neuron disease pa
studies and needle electromyographic evidence of denervation tients, resulting in an ill-defined annual incidence of about
and reinnervation with upper motor neuron signs suggests a di 0.21100,000 population. 116,517 For the purposes of the chapter,
agnosis of ALS. Of course, the profound autonomic findings are we will primarily concentrate on ALS with mention of addi
not usually noted in ALS, and thus the Shy-Drager syndrome tional syndromes where appropriate.
should be considered. A few patients have had reduced-ampli Amyotrophic lateral sclerosis (ALS) is a progressive, degen
tude SNAPs and slow sensory nerve conduction studies,276.800 erative disease affecting both the upper and lower motor neu
These same individuals have reduced CMAPs and slow motor rons. ALS has an incidence of 0.4-3.0 per 100,000 and a
conduction studies. Needle electromyographic examination prevalence of 4-6 cases per l00,OOO.275,315.345.4SM58,517The aver
documents positive sharp waves and fibrillation potentials com age age of ALS onset is between 52 and 66 years,230,316.412.455.669,828
bined with a reduced number of large-amplitude long-duration Most cases of ALS are sporadic, but as many as 10-15% of
MUAPs. cases are inherited, so-called familial ALS (FALS).368.568,792.828
Approximately 25% of FALS are caused by mutations in the
Polyglucosan Body Neuropathy gene encoding copper-zinc (CuJZn) superoxide dismutase
Polyglucosan body neuropathy is a variant of glycogen stor (SODl).677 There is a slight male predominance (3:2 male-to
age disease (GSD) type IV caused by a deficiency in branching female ratio) in sporadic ALS, while the male-ta-female ratio is
enzyme. Classically, branching enzyme deficiency presents in 1: 1 in familial ALS.169
infants as failure to thrive associated with liver failure and The sporadic ALS and FALS forms of ALS are clinically and
splenomegaly. Some patients have their disease manifested with pathologically similar. The median survival is approximately 3
a myopathy involving skeletal and cardiac muscle. Finally, there years. The course of ALS is relentless with a linear decline in
is a form GSD IV that presents in adults with progressive upper strength with time during the active phase of the disease. 103.345,569
and lower motor neuron loss, sensory loss, neurogenic bladder, An older age, onset in bulbar muscles, lower pulmonary function
cerebellar ataxia, and dementia in various combinations. 114,124,498,914 tests, and reduced serum chloride levels (an indicator of respira
Nerve conduction studies reveal features of an axonal sensory tory acidosis) are associated with shorter survival. 116,517.589,788 A
motor polyneuropathy, while the needle electromyography ex rare form of autosomal recessive familial and occasionally spo
amination demonstrates evidence of active denervation and radic form of ALS is known as juvenile ALS.326 It has a mean
reinnervation in a polyradicular or generalized pattern. The dis onset age of 12 years (3-25) and appears identical clinically to
order is discussed in more detail in the hereditary myopathy adult ALS except for a much slower progression. 327,328
chapter (Chapter 27) along with the laboratory, histologic, and ALS researchers from around the world gathered in EI
electrodiagnostic features. Escorial, Spain, in 1990 to devise criteria for the diagnosis of
ALS.896 A clinical diagnosis of "definite ALS" requires the pres
Amyotrophic Lateral Sderosis (ALS) ence of UMN and LMN signs in the bulbar region as well as at
Approximately 5-10% of ALS is inherited. Familial ALS least two of the three other spinal regions (i.e., cervical, tho
(FALS) is indistinguishable clinically or electrophysiologically racic, and lumbosacral). "Probable ALS" is defined by the pres
from sporadic ALS (SALS). The pathogenic basis of familial ence of UMN and LMN signs in at least two regions (some
ALS may shed insight into sporadic ALS. Therefore, we dis signs must be rostral to the LMN deficits). "Possible ALS" re
cuss FALS and SALS in the next section under the acquired quires UMN and LMN signs in only one region, UMN signs
disorders. alone in two or more regions, or is diagnosed when the LMN
signs are rostral to the UMN signs. Electrophysiologic criteria
ACQUIRED DISORDERS AFFECTING for definite LMN degeneration include: (1) the presence of fib
MOTOR NEURONS rillation potentials; (2) large amplitude, long duration MUAPs;
and (3) reduced recruitment. EMG evidence of LMN degenera
Motor Neuron Disease/Amyotrophic Lateral Sclerosis tion in two muscles supplied by two different nerve roots and
nerves in a limb can substitute for clinical evidence of LMN
Clinical Features. The terms motor neuron disease and loss in the limb. Fulfilling the EI Escorial Criteria for definite
amyotrophic lateral sclerosis (ALS) are frequently used inter or even probable ALS can be difficult even for patients with ad
changeably. Motor neuron disease, however, can be thought to vanced disease. Thus, less stringent criteria have been devised
consist of four different clinical syndromes that may all be vari and have proven useful in enrolling patients in clinical research
ations of the same basic disease: (1) progressive muscular at trials earlier in the course of their illness. 97,684 Many of the
rophy (anterior hom cell loss, no upper motor neuron recent studies have required clinical and electromyographic evi
involvement-UMN); (2) adult-onset progressive bulbar dence of LMN involvement in two regions and UMN signs in
palsy (preferential degeneration of bulbar nuclei not associated one region.
with significant spinal anterior hom cell dysfunction or upper Many patients exhibit only lower motor neuron signs or
motor neuron signs); (3) primary lateral sclerosis (corti purely upper motor neuron signs early in the course of the dis
cospinal tract involvement sparing the lower motor neurons- ease. Less than 10% of patients remain with only lower motor
602 - PART IV CLINICAL APPLICATIONS
neuron abnonnalities (PMA), and even fewer patients have well as accompanying dorsal root ganglion 10SS. 3•92.2 18.517.669.741.891
only upper motor neuron deficits (PLS) throughout the ill This suggests that ALS is a neurodegenerative disorder that is
ness.34S.804.828 Some patients with long-standing PLS went on to not restricted solely to motor neurons.
develop LMN abnormalities up to 27 years after the onset of Molecular Genetics and Pathogenesis. Only 5-10% of
UMN signs. 1I7 Some patients with FALS and defined mutations ALS is inherited. 747 Approximately 25% of cases are due to au
in the SOD 1 gene have limited, if any, clinical or pathologic in tosomal dominant mutations in the copper-zinc (CnlZn) SODI
volvement of the corticospinal tracts. 170 Therefore, PMA, PLS, gene on chromosome 21. 677 Interestingly, there is marked clini
and ALS likely represent a spectrum of the same disease rather cal heterogeneity caused by different mutations in the SODI
than distinct entities. gene. 3O,169,413 For example, patients with the A4V mutation usu
Lower motor neuron involvement manifests as weakness, at ally survive less than 1 year, whereas patients with G37R muta
rophy, and fasciculations. Muscle cramps are also quite tion have long survival periods. The D90A mutation is
common. Upper motor neuron lesions manifest as spasticity and associated with early sensory abnonnalities and a long survival
slowness of movements in addition to weakness. Deep tendon of over 15 years. The pathogenic mechanisms by which muta
reflexes are brisk and demonstrate abnormal spread, if not tions in the CulZn SODI gene lead to motor neuron cell death
actual clonus. Sometimes reflexes are not particularly hyperac has been the subject of intense research (see below).
tive secondary to severe lower motor neuron involvement. Because 75% of FALS are not the result of mutations in the
Nevertheless, the clinician may feel the reflexes are brisk com SODl gene, it is apparent that FALS is genetically hetero
pared with the degree of muscle wasting indicating probable geneic. A large autosomal dominant family with juvenile onset
upper motor neuron pathology. Upper motor neuron signs in of distal atrophy and weakness localized to chromosome 9q34
clude an increased jaw jerk, enhanced gag reflex, suck or snout has been noted. 652 In addition, autosomal recessive forms of ju
reflexes, and extensor plantar responses. The patient may have a venile-onset ALS have been linked to chromosomes 2q33-35 370
scissoring or spastic type of gait. and 15q15-q22. 351 The genes for these other fonns of FALS
In the limbs, muscle weakness and atrophy usually begin have yet to be identified. Much more work is necessary to un
asymmetrically and distally and then spread within the neuraxis ravel the etiology of the bulk of FALS.
to involve contiguous groups of motor neurons. Bulbar involve The cause of sporadic ALS is unknown. 804·891 A viral etiology
ment manifests initially as dysphagia or dysarthria. Inspection was initially fueled by a reported relationship between the po
of the tongue may reveal atrophy and fasciculations. There is liomyelitis virus or perhaps other enteroviruses and patients
relative sparing of muscles of eye movement and the urinary with ALS.66.838 One study detected enterovirus RNA sequences
sphincters. Respiratory muscles are affected late in leg-onset in cell bodies of the anterior horns in post-mortem spinal cords
patients, but occasionally can be an early manifestation in pa of 15 of 17 patients with ALS.69 However, a cause-and-effect re
tients with bulbar-onset symptoms. Rare patients present with lationship between possible viral infections and ALS has not
acute respiratory failure. 139 A few patients manifest only bulbar been finnly established.424
weakness throughout the course of the disease (progressive Approximately 1% of sporadic ALS patients have mutations
bu\barpalsy). Occasionally, patients have slowly progressive bi in the heavy chain subunit ofneurofilament protein (NF-H).258
lateral upper limb weakness and atrophy sparing of the bulbar However, the significance of this finding is not clear. Of note,
and lower limb muscles-the so-called Dail arm syndrome or mutations in NF-H have not been identified in any FALS kin
brachial amyotrophic diplegia.375.428.716 ships.674,849 Because of their clinical, histopathologic, and elec
The vast majority of patients with ALS have nonnal sensa trophysiologic similarities, insight into the pathogenic basis of
tion. However, quantitative sensory testing has revealed slight PALS may increase our understanding of the pathogenic basis of
sensory abnonnalities in about 17% of ALS patients.567 Mental the more common sporadic ALS .106 The major hypotheses re
function is well preserved in most persons; however, dementia garding the pathogenic basis of ALS include free radical-medi
may rarely occur. Patients may demonstrate a pseudobulbar ated oxidative cytotoxicity,253.677 glutamate excitoxicity,144.689-693
affect (i.e., emotional lability). mitochondrial dysfunction,S7.7IS and autoimmune disease. 765
Histopathology. Upon gross inspection of the central ner These possible hypotheses are not mutually exclusive, and the
vous system, precentral gyrus atrophy as well as reduced diam pathogenic basis of ALS may involve interplay of each or some
eter hypoglossal and anterior spinal nerve roots can be part of each mechanism (Fig. 16-14). Below we briefly outline
noted. 142,570,61S.838 A size decrease and sclerosis of the anterolat the major hypotheses in regard to the pathogenic basis of ALS.
eral spinal tracts are observed, while there is good preservation The Free Radical/Oxidative Damage Hypothesis. As noted
of the posterior columns. Microscopic inspection of the spinal above, approximately 25% of FALS are caused by mutations in
anterior hom cell and bulbar regions reveals considerable loss the gene for cytosolic, CulZn superoxide dismutase (SOD1).617
of motor nerve nuclei as well as gliosis.356.357.43O Of note, the 3rd, To date, at least 60 different mutations in SOD I have been de
4th, and 6th cranial nerve nuclei are relatively spared. Degen scribed in FALS. SOD I is a metalloenzyme of about 153 amino
eration of other types of neurons are seen as well and includes acids that is expressed in the cytoplasm in all eukaryotic cells.
those of Clarke's nucleus, the substancia nigra, and the cerebral The SODl enzyme catalyzes the conversion of superoxide
cortex. Intracytoplasmic inclusions (Le., Bunina bodies, anion to hydrogen peroxide (H20 2) (Fig. 16-14).323 Next, hy
ubiquinated skein-like inclusions, and Lewy bodies) may be drogen peroxide is converted to water in enzymatic reactions cat
seen in a motor neuron cell bodies.356.357 The proximal axons of alyzed by cytosolic glutathione peroxidase (GSHP) or
motor neurons demonstrate focal swellings composed of neuro peroxisomal catalase. These reactions are essential because su
filaments (spheroids). peroxide is a free radical capable of inducing neuronal damage.
Muscle biopsy demonstrates grouped atrophy and occasion Furthermore, superoxide anions may also be converted to highly
ally fiber type grouping consistent with a neuropathic reactive hydroxyl radicals hydroxy anions (OH-) via interaction
process.870.883 In some patients, there is evidence of mild sensory with reduced transition metals such as Fe2+ or Cu l + or via inter
fiber degeneration in the sural and superficial peroneal nerves as action with Fe3+:
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 60J
fmp.f,.d Mltoo/tondrl.
".-==~
F~=J
F"."::: ::J
--= - CELL DEATH
I
ExcllotolClclty MutantSOD1
NO
Figure 16-14. Pathogenic basis of ALS. Possible relationships between SOD 1 mutations. glutamate excitotoxicity, nitrotyrosination. and mi
tochondrial dysfunction. Normally, superoxide is detoxified by SOD I to hydrogen peroxide and that is subsequently converted to water by cata
lase and glutathione. Mutant SOD I may fail to buffer neurotoxic metals (i.e.• zinc and copper). Further, mutant SOD I may secondarily result in the
increased concentration of superoxide anions that enhance the formation of peroxynitrate. Peroxynitrates may induce cellular injury by nitrating
tyrosine residues on proteins or by increasing the formation of reactive hydroxyl radicals. Excitatory transmitters such as glutamate may induce
cytosolic calcium that initiates the cascade of proteolysis and perhaps apoptosis and enhance the formation of superoxide and nitric oxide. The
effect of glutamate toxicity and SOD I mutations may have a facilitory effect. (From Brown RH Jr:Amyotrophic lateral sclerosis: Recent insights
from genetics and transgenic mice. Cell 1995;80:687~92, with permission.)
However, superoxide dismutase and catalase activities were primary mediators of excitotoxicity. The excitatory action of
normal in both regions compared with controls. The reduction glutamate is normally terminated by its rapid removal from the
in GSHP activity in the precentral gyrus correlated with disease synapses by binding to high-affinity glutamate transporters
duration. This reduction could be an epiphenomenon or may be (EAATl, EAAT2, EAAT3). In this regard, EAAT2 and EAAT3
an important cause of cytotoxicity by increasing levels of hy are found on astrocytes, while EEAT3 is found on neurons. 69 1.692
drogen peroxide. 548 However, other investigators have not Excessive concentrations of glutamate leads to neuronal
demonstrated the reduction in GSHP activity in the CNS.273,384 death in both in vitro and in vivo models. 142 Increased activation
One study reported increased GSHP activity in the spinal cord of the glutamate receptor results in depolarization and influx of
tissue of sporadic ALS,384 while another found no significant sodium, chloride, and calcium into the cell. The influx of cal
difference in GSHP activities in the spinal cords of sporadic cium in tum is thought to activate various enzymes including
ALS compared with normal controls. 273 proteases, nucleases, and other enzymes (e.g., xanthine oxidase,
Because free radicals are highly reactive and short-lived, bio nitric oxide synthase) that increase the production of free radi
chemical markers are necessary to indirectly assess the extent of cals that ultimately lead to cell death (Fig. 16-14). In regard to
oxidative damage to DNA, proteins, and lipids. Oxidative the glutamate excitotoxicity theory, Rothstein and colleagues
damage to DNA results in the formation of 8-hydroxy-2-de demonstrated that glutamate levels are increased in the CSF and
oxyguanosine (OH8dG).26 Oxidation of proteins correlate with brain in some cases of sporadic ALS.689 Subsequently, they
the appearance of protein carbonyl groups in plasma and in showed that high-affinity glutamate uptake was decreased in
tissue. 266 As noted above, 3-nitrotyrosine is a marker for protein synaptosomes prepared from the spinal cord and motor cortex
oxidation mediated by peroxynitrite. Lipid peroxidatioIl results in subjects with ALS.690 Next, the expression of the glial (astro
in the production of malondialdehyde. 319 Oxidative stress also cytic) glutamate transporter, EAAT2 (previously known as GLT
induces the enzyme heme oxygenase-I (HO-I), whose activity 2), was found to be diminished in sporadic ALS.69t.692 In
likewise is measurable.217 contrast, EEATl and EAAT3 were normally expressed. No mu
In regard to the above discussion of biologic markers of ox tations in the gene encoding EAAT2 have been demonstrated.
idative stress, autopsy studies have demonstrated increased However, abnormally spliced mRNA transcripts for EAAT2
levels of protein carbonyl groups in the frontal cortex,89 motor were found in brain tissues of 60% of patients with sporadic
cortex,253 and spinal cords 738 in sporadic ALS patients compared ALS.488 These abnormal mRNA species contain intron 7 or skip
with patients with FALS and normal controls. One study found exon 9. Both of these aberrant mRNA transcripts form non
increased levels of OH 8dG in sporadic ALS motor cortex but functional truncated proteins that may inhibit normal EEAT2
not in FALS patients. 253 Immunohistochemical studies have mediated transport. Finally, treatment with riluzole, a glutamate
shown increased neuronal staining for HO-I, malondialdehyde, release inhibitor, modestly improves survival in ALS patients.
and OH8dG in both sporadic ALS and FALS spinal cord.56.253 The Mitochondrial Dysfunction Hypothesis. Because mito
Several groups have found increased tyrosine nitration in spinal chondria transfer electrons to oxygen, they are a likely source of
cord tissue of both sporadic ALS and FALS patients with SOD I reactive oxidants. In turn, these free radicals may impair mito
mutations as well as in transgenic mice expressing SOD I muta chondrial function.s3 Mitochondria abnormalities are evident in
tions.112.253 Beal and colleagues found significant increases in various tissues in sporadic ALS and FALS patients as well as in
concentrations of malondialdehye in the cerebral cortex and in transgenic ALS mice.57.356.577.715.856 In SALS subjects, abnormal
creased immunostaining for 3-nitrotyrosine, heme oxygenase-I, accumulation of mitochondria and reduced complex I activity
and maiondialdehyde modified protein throughout the spinal are found in motor neurons and muscle. Mitochondrial dysfunc
cord of the transgenic ALS mice. 57.5s tion may lead to ATP depletion and contribute to cell death.
Finally, the mutant SODI protein may be directly toxic to Abnormal Neurofilaments Hypothesis. Abnormal accumula
neurons. Mutant SOD appears to be pro-apoptotic, whereas tion of neurofilaments are seen in the cell body and proximal
normal SOD is anti-apoptotic.216.287 In this regard, postmortem axons of motor neurons in ALS patients' brains and spinal cords.
studies of human ALS spinal cords demonstrate DNA fragmen Approximately 1% of patients with sporadic ALS have small mu
tation that is seen with apoptosis.903 Transgenic mice with the tations in the large neurofilament subunit (NF_H).t7.258 However,
SOD 1 mutations reveal increased expression of Bad, Bax, cas there is no direct evidence that the NF-H mutations were the pri
pase-I, and caspase-3 (pro-apoptotic factors) and reduced ex mary cause of ALS in these patients. Mutations in the NF-H gene
pression of BcI-2 and BcI-xL (anti-apoptotic factors).487.859 have not been identified in any FALS kinships.674.849
Interestingly, treatment of these transgenic mice with caspase The Autoimmune Hypothesis. Some authorities postulate an
inhibitors prolongs survival in this animal model of FALS.272A87 autoimmune basis for ALS.765 Inflammatory cells and im
The Glutamate Excitotoxicity Hypothesis. There are several munoglobulins may be evident in ALS brains and spinal cords.
lines of evidence suggesting glutamate excitotoxicity in the The clinical significance of these findings are not clear, and they
pathogenesis of ALS.I44.689-692 Glutamate is the major exitatory may just represent an epiphenomenon. There is an increased in
neurotransmitter in the CNS. When the presynaptic nerve termi cidence of paraproteinemias and malignancies, in particular
nal is depolarized, glutamate is released into the synaptic cleft, lymphoproliferative disorders, in patients with ALS.269.305.907
where glutamate binds the two major categories of receptors: However, immunosuppression with corticosteroids, cyclophos
inontropic receptors and metabotropic receptors. The ionotropic phamide, plasmapheresis. and total lymphoid irradiation fail to
receptors are ligand-gated cation channels, whereas the halt the progression of the disease. 107.210,810 Also, treatment of
metabotropic receptors are linked to G-proteins and second any associated lymphoproliferative disorder likewise does not
messenger systems. The ionotropic receptors are divided into halt the progression of motor neuron loss.
three classes according to their affinities for specific agonists: Electrophysiologic Findings. The electrodiagnostic medi
(1) N-methyl-D-aspartate (NMDA); (2) a-amino-3-hydroxy-5 cine examination is important in confirming whether a patient
methyl-4-isoxaole proprionic acid (AMPA); and (3) kainate re clinically suspected of having the disease does in fact have
ceptors. The AMPA and kainate receptors are thought to be the ALS.61,181a Initial electrodiagnostic criteria required for the
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 60S
diagnosis of ALS devised by Lambert included the following dysfunction, an alteration in the slower conducting sensory
documentation: (l) positive sharp waves andlor fibrillation po nerve fibers should not be surprising. A reduction in amplitude
tentials documented in three limbs or two limbs and bulbar mus and subsequent mild slowing of SNAPs as recorded by routine
cles with the head counting as a "limb"; fasciculation potentials findings may also be possible if the patient survives long
in the upper and lower limbs, or upper!lower limbs and bulbar enough for the majority of the fastest conducting fibers to
muscles may also be detected; (2) normal sensory nerve con become affected producing both a decline in maximal conduc
duction studies; (3) normal motor nerve conduction velocities tion velocity and amplitude.327 The sympathetic skin response
unless the CMAP is significantly reduced « 30% of the mean), may be absent or prolonged in latency in ALS patients, suggest
in which case the conduction velocity may not be less than 70% ing concomitant involvement of the autonomic nervous
of the mean for the nerve under investigation; and (4) needle system. 193 More controlled studies exploring this interesting
electromyographic examination demonstrates a reduced recruit aspect of ALS electrophysiology are needed to better define the
ment with altered MUAP parameters in terms of duration and presence of subtle sensory conduction abnormalities.
amplitude.463.464 EI Escorial criteria requires (1) the presence of Evoked Potentials. Brain stem auditory evoked responses
fibrillation potentials; (2) large-amplitude, long-duration and visual evoked potentials are normal in persons with ALS.
MUAPs; and (3) reduced recruitment in two muscles supplied The results of somatosensory evoked potentials in patients with
by two different nerve roots and nerves in a limb can substitute ALS are controversial. A number of reports using both median
for clinical evidence of LMN loss in the Iimb. 896 However, many and tibial nerve SEP techniques have documented an abnormal
patients with ALS do not fulfill these electrodiagnostic criteria SEP in up to 60% of patients.85.163.180.288,432,525.653.795 It is not always
until late in the course of their disease. clear as to whether there is a central or peripheral conduction
Although a universal protocol does not exist, we perform abnormality, but in some patients a central conduction abnor
motor and sensory studies on at least one upper and lower limb. mality predominates, while in othbrs a peripheral abnormality is
Likewise, needle electromyography is done on the above limbs present. On the other hand, several well-performed investiga
as well as the thoracic paraspinal muscles. If the patient has tions have failed to document any form of abnormality with
bulbar symptoms or signs, the tongue, and facial muscles are either upper or lower limb SEP techniques.I33.202.598.606 These in
examined. At times, the question arises as to what extent the vestigations have criticized those studies finding SEP abnormal
nerve conduction changes are due to ALS versus some other ities in ALS patients as not having critically accounted for other
process. As a rough guide, the distal motor latency should not problems likely to generate an abnormal SEP. For example, not
exceed 125% of the upper limit of normal, motor conduction all investigations explored the possibility of a peripheral neu
velocity should not fall below 70% of the lower limit of normal ropathy existing concomitantly with ALS. Also, SEPs can be a
(some persons use a mean as opposed to lower limit value) but useful study in documenting cervical spondylosis. As most pa
is rarely less than 80% of the lower limit of normal, and the F tients with ALS are also likely to have age-related cervical spine
wave latency should not exceed 12% of the upper limit of abnormalities, care must be exercised in distinguishing between
normal. 161 If findings exceed these values, a peripheral neuropa abnormal SEPs arising from cervical spondylosis versus ALS.
thy may be present accounting for the changes, but this does not Loss of muscle mass can lead to reduced limb temperatures,
preclude ALS from also being present. which in turn can delay SEP waveforms. A very important
Sensory Nerve Conduction Studies. Upper and lower limb aspect to consider involves the normal aging changes affecting
sensory nerve conduction studies are generally considered to be the peripheral nervous system that may result in some SEP de
normal with respect to all SNAP parameters.18Ia.238.260.290.414 viation from anticipated normals. Those investigations taking
Similar findings have been reported in primary lateral sclero care to eliminate the above noted variables fail to find either pe
sis.703 A few investigators have reported mild to moderate SNAP ripheral or central SEP conduction defects, thus suggesting that
abnormalities as manifested by reductions in amplitude or con most patients with ALS should have normal SEP studies and
duction velocities at times approaching 22% of all ALS patients when an abnormality is detected a search for another disease
examined.I09.310.561.891 These findings have generally been criti entity should be pursued prior to attributing this finding to ALS.
cized with respect to not taking temperature sufficiently into ac Additional large-popUlation studies taking care to control for
count, entrapment neuropathies possibly being present, or multiple variables is required to fully address this issue.
failing to consider normal changes with aging as accounting for Motor Nerve Conduction. Routine motor nerve conduction
most of these SNAP problems. When all of these factors are studies usually demonstrate normal conduction velocities in most
considered, a few patients may remain with unexplainable patients with ALS and primary lateral sclerosis provided tempera
SNAP parameter abnormalities. 891 These findings are supported ture is appropriately maintained at 32°C or higher.92.703,804 There
by the variable but present abnormal histopathologic findings in can be a mild reduction in maximal motor nerve conduction veloc
some persons with unmistakable ALS. The majority of these in ities, usually less than 70% of the lower limit of normal in some
vestigations explored the maximal conduction velocities of sen persons with ALS. Of note, although the maximal mean nerve
sory nerves using surface recording techniques. If near-nerve conduction velocities in patients with ALS are within normal
needle techniques are utilized to place a recording electrode as limits, when compared with age-matched controls there is a con
close as possible to the nerve, it becomes possible to detect mul siderable reduction. 575 Similarly, minimal motor nerve conduction
tiple baseline irregularities following the major SNAP spike velocities are also reduced. The difference between the maximal
representing subpopulations of slower conducting nerve fibers and minimal nerve conduction velocities in both normal and con
undetectable with surface recording electrodesJ39 When the trols is essentially the same, indicating a uniform reduction in
slowest conducting nerve fibers are examined, 50% of patients those caliber motor fibers mediating motor nerve conduction.
with ALS demonstrated a reduction in this parameter compared A mild prolongation in the distal motor latency may also be
with a control population. Given the above-described sensory detected in these patients. !85.191 These findings directly corre
nerve histopathologic findings suggesting a sensory neuronopa spond to the amplitude of the CMAP. As the CMAP declines, a
thy in addition to the more generally accepted motor systems commensurate reduction in nerve conduction velocity may also
606 - PART IV CLINICAL APPLICATIONS
be observed. The CMAP amplitudes decline over the course of High-voltage electrical fields using either monopolar or bipo
the illness corresponding to the loss of motor units.18S.247.S75 Very lar stimulation techniques can demonstrate abnormalities of
low CMAP amplitudes (e.g., less than 20% of the lower limit of central motor conduction in patients with ALS; however, they
normal) imply profound anterior horn cell loss and are associ are uncomfortable and thus of limited clinical utility. Magnetic
ated with a poorer prognosis.1 81 cortical stimulation appears to be a useful method of exciting
F-wave latency is normal or only slightly prolonged com the motor cortex with minimal side effects. In patients with only
mensurate with axon IOSS.16.37.52.185.632 Some patients, particularly UMN signs, magnetic stimulation may fail to evoke a response
those with small-amplitude CMAPs may not have demonstrable from the abductor pollicis brevis, extensor digitorum commu
F-waves. 52 The increase in F-wave latency and decrease in con nis, and biceps brachii muscles or demonstrate central conduc
duction velocity are attributed to the progressive loss of fastest tion delay. Further, decreased, corticocortical inhibition is seen
conducting nerve fibers owing to the disease process. Increases on paired transcranial stimulations compatible with impaired
in distal motor latency is somewhat similar to a dying back neu function of inhibitory interneuronal circuits in the motor cortex
ropathy and may be a result of some form of dying back in of ALS patients.913 The utility of this transcranial magnetic stim
motor neuron disease. 92 An increase in ease of eliciting H-re ulation is in patients who are suspected of ALS but have primar
flexes in muscle not normally yielding this potential may be ob ily UMN signs (i.e., PLS), in which case routine needle
served in some patients. electromyographic and nerve conduction studies are normal. I10
Patients with ALS should not have conduction block on the Motor Unit Number Estimation (MUNE). As we know, the
motor conduction studies. There are reports of CMAPs display CMAP is obtained by supramaximal stimulation of a mixed or
ing what appears to be motor nerve conduction block.468.834.893 pure motor nerve and represents the summated electrical activ
However, these findings are criticized on the basis of the few re ity of the functional motor units of the underlying muscle. The
maining motor units displaying a resultant phase cancellation as CMAP is the summation of individual single motor unit action
a result of the normal temporal dispersion in the peripheral potentials (S-MUAP). If the average S-MUAP can be deter
nerve conduction but magnified secondary to the combination mined, one can surmise the total number of single motor units
of few remaining motor units and increased MUAP duration. 799 innervating the muscle of interest. The MUNE can be calculated
Stimulating the nerve more proximally permits the few remain form the simple formula: MUNE = CMAP amplitude or
ing motor units to progressively move out of phase with respect area/average S-MUAP amplitude or area. 2M
to each other, thus phase canceling. This is not observed under There are four widely used techniques for MUNE: (1) incre
normal conditions because of the large number of motor units mental stimulation, (2) multipoint stimulation, (3) the statistical
nullifying this effect, which becomes apparent only as the total method, and (4) spike-trigger averaging. 303 MUNE has potential
number of motor units decline. value in tracking the natural history of motor neuron survival
Repetitive Stimulation. If repetitive stimulation is performed and the effect of potential therapeutic agents in patients with
at slow rates (3 Hz) in patients with ALS, about half may ALS. Dante and McComas used incremental stimulation to
demonstrate some form of CMAP decrement between the first follow MUNE in 373 muscles in 123 ALS patients (74 patients
and fifth response. 72,I90.439,759 The character of this decrement is were studied at least twice).177 MUNE progressively declined in
similar to that observed in myasthenia gravis with respect to the majority of patients with approximately a 50% loss of motor
repair following exercise and an increase several minutes fol neurons every 6 months during the 3-year study, MUNE deter
lowing exercise. The decrement is less than 20-25% and is re mined with incremental stimulation correlates well with quanti
paired by a drop in temperature, thus necessitating the same tative muscle strength testing and survival. 40,41 Multipoint
precautions as those exercised in neuromuscular junction disor stimulation MUNE also appears reproducible and possibly
ders. A decrement is more likely to be detected in an atrophic useful in tracking motor unit loss in ALS.IOO,IOI,137,249,250,302 One
muscle and is especially likely to be recorded in persons who study noted that the rate of decline in MUNE was more sensi
have a relatively rapid form of the disease. Also, a muscle that tive than manual muscle testing of strength and measurements
has significant fasciculation potentials is more likely to demon of forced vital capacity.250 In one study, 10 ALS patients were
strate a decrement to repetitive stimulation. The recording of a studied at baseline, 3 months, and after 6 months using the sta
decrement is expected given the needle electromyographic find tistical MUNE of the adductor digiti minimi.<Xl9 MUNE declined
ings of unstable MUAPs and single-fiber electromyographic approximately 50% at 6 months, which was much more sensi
documentation of elevated jitter (see beIOW).781 All of these find tive than the mild deterioration in the CMAP and grip strength.
ings are consistent with newly formed collateral sprouts main The rate of MUNE decline correlated with a shorter survival.
taining tenuous neuromuscular junction connections subject to The statistical method also appears to be reproducible in calcu
failure secondary to a reduced safety factor. Microelectrode as lating MUNE in ALS patients, an important criterion for ALS
sessment of ALS neuromuscular junctions reveal decreases in trialS. 496,1i01 The spike-trigger averaging technique for assessing
all of the following: size of the nerve terminal, miniature end MUNE has also be employed in patients with ALS.98,99.793
plate potential amplitudes, mean quantal content, number of However, one study demonstrated there is less reproducibility
quanta available for immediate release, and mean quantal with this technique and MUNE poorly correlates with isometric
stores. All of these factors contribute to a reduced safety factor muscle strength.98
and hence the above-noted findings. sls Patients with an aggres Needle Electromyography. The needle electromyographic
sive form of the disease have a decrement because of the rapid examination is perhaps the most important of the electrophysio
ity with which anterior horn cells are lost and the formation of logic tests performed, As noted above, it is a good idea to exam
multiple new neuromuscular junctions through collateral ine at least one upper and lower limb in addition to the
sprouting, corresponding thoracic paraspinaJ muscles and bulbar muscles.
Motor Evoked Potentials. Transcranial magnetic stimula Within a limb, muscles innervated by different roots, trunks of
tion65 ,18Ia,227,228.726.804,830,832,841,913 and high-voltage electrical fields 66,386 the plexus, and nerves should be thoroughly examined for abnor- .
can be used to activate the cerebral motor cortex directly. mal spontaneous activity at rest (positive sharp waves, fibrillation
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 607
potentials, fasciculation potentials), MUAP recruitment, and muscle and left in place with the examining hand removed and
MUAP morphology. In individuals with primary lateral sclero the instrument's screen observed for approximately I minute.
sis, there are no abnormalities typically noted during needle Fasciculation potentials may arise at any location along the
electromyographic examination. 703 lower motor neuron from the anterior horn cell region to the
The demonstration of active denervation (i.e., positive sharp distal terminal nerve arborization near the neuromuscular junc
waves and fibrillation potentials) is the most important aspect of tions. I60,688,872 There is really no way to reliably distinguish be
the needle electromyographic examination in patients with tween so-called pathologic and benign fasciculation potentials
ALS.92,581,804 This general statement must be tempered with a re based solely on their morphology or discharge frequency irre
alization that ALS is a progressive disease with different electro spective of studies that claim benign compared with malignant
physiologic manifestations depending when during the disease fasciculation potentials fire rapidly (1/0.8 sec versus 1/3.5
course an individual is examined. If a patient is examined during sec).833 However, rapid firing fasciculation potentials have also
the early course of the disease process, positive sharp waves and been associated with aggressive disease states, disorders with
fibrillation potentials may be difficult to detect. The main reason high degrees of collateral sprouting and increased jitter, or
for this failure is the efficiency of collateral sprouting compared motor units with recently acquired muscle fibers through collat
with the time necessary for muscle fibers to fibrillate. It may take eral sprouting. 397 Of course, slow firing fasciculation potentials
a week or more for muscle membranes to reach a sufficient level may also be associated with disease, but more so a slowly pro
of instability in order to discharge spontaneously, whereas col gressive process and not necessarily the absence of any disease,
lateral sprouting may occur within 5-10 days. Thus, it is possi Fasciculation potentials are more stable and easier to recruit
ble in patients with slowly progressive disease to have a few voluntarily in the early phase of ALS, while they are more un
anterior horn cells fail with muscle fibers subsequently dener stable, complex, and difficult to recruit later in the course of the
vated, but the neighboring intact motor units providing collateral disease. The best method of deciding if a fasciculation potential
sprouts that reinnervate these orphaned muscle fibers. Hence, in is associated with a disease state is to critically evaluate the
these individuals membrane instability may not be prominent be company it keeps in terms of the presence of abnormal sponta
cause of efficient collateral sprouting. It is, therefore, particu neous activity (i.e., fibrillation potentials and positive sharp
larly important in persons with early disease to have a careful waves). If the single muscle fiber components of a fasciculation
and extensive examination of multiple muscles and limbs includ potential have an increase in jitter, or are observed to vary con
ing the thoracic paraspinal region and craniobulbar muscles, as siderably in shape from one discharge to the next with routine
these regions are commonly involved in ALS patients and not needle electromyography, it is likely that the potential is abnor
likely to be affected in cervical spondylosis or disk disease mas mal.876 This supposition is justified because the increase in jitter
querading as ALS.262,452,646 As the disease progresses and more as measured directly or indirectly through fasciculation poten
anterior horn cells are lost, the efficiency and capacity of surviv tial variability is a result of immature neuromuscular junctions
ing motor units to incorporate denervated muscle fibers may and motor unit remodeling, which should not be present in pa
become progressively reduced with a concomitant increase in tients with benign fasciculation potentials.
fibrillation potentials. 243 Also, although unknown, it is believed When evaluating a patient, an important aspect of the needle
that each anterior horn cell has a finite capacity of the number of electromyographic examination is MUAP recruitment analysis.
muscle fibers capable of being innervated. At some point, it is The majority of patients (86%) with ALS demonstrate recruit
conceivable that as this maximum number is approached, it may ment abnormalities, even those examined during the early
take longer to establish viable neuromuscular junctions or a course of the disease.243 Loss of anterior horn cells is noted by
steady state is reached in which new muscle fibers are acquired failure of the MUAPs innervated by those cells to fire at the ap
with the consequence of losing previously innervated muscle propriate time with respect to neighboring motor units. A rough
fibers. The net result of these admittedly speculative assertions is rule of thumb is that the mean firing frequency of the MUAPs
an increasing number of denervated muscle fibers with progres divided by the number of different MUAPs firing should
sively more time to develop spontaneously discharging muscle roughly equal 5, i.e., the recruitment ratio. 181 A reduced recruit
membranes. Therefore, patients with progressively longer dis ment in an ALS patient is exemplified by the fastest motor unit
ease durations tend to demonstrate increasing numbers of fibril firing at 20 Hz with only two motor units on the screen and a
lation potentials in more and more muscles in addition to more recruitment ratio of 10. Only the first two motor units need be
limbs with abnormalities including the cranial musculature. The recruited to calculate this number. Any ratio equaling or exceed
maximum degree of these spontaneous potentials is usually de ing 10 may be considered abnormal for limb muscles.
tected in persons having the disease for about 1.5-2 years. 243 In addition to MUAP recruitment, the MUAP's parameters
After some time, there may be a gradual decline in spontaneous should also be assessed. 120 The process of collateral sprouting
activity as there are insufficient anterior horn cells left to reinner leads to a number of characteristic findings. 806 An increase in the
vate muscle fibers, and the remaining denervated muscles fibers number of muscle fibers per motor unit usually results in more
atrophy and fibrose, thus losing the ability to fibrillate. Complex voltage being recorded and hence a large amplitude potential.
repetitive discharges also may be observed in some persons with Some individuals with ALS have been reported to have a few
ALS, although these are not particularly prominent in most pa MUAPs approaching or exceeding 10 mY. These MUAPs may
tients.235 Needle examination of the anal sphincter muscles initially be increased in duration secondary to a decreased syn
demonstrates normal findings even in patients with marked limb chronization of impulse arrival at all of the neuromuscular junc
abnormaiities. 710 tions as a result of immature collateral sprouts as well as some
Fasciculation potentials are usually the earliest abnormality muscle fiber size variation resulting in muscle fiber conduction
noted in persons with ALS, provided sufficient patience is exer velocity dispersion. The decreased synchronous firing cannot
cised. 243 ,360 The firing rate of fasciculation potentials can be only increase the potential's duration, but also lead to an increase
highly irregular, 184 When one is attempting to observe fascicula in the number of polyphasic MUAPs. With time, the temporal
tion potentials, the needle electrode must be placed within the dispersion of muscle fibers discharging decreases owing to
608 - PART IV CLINICAL APPLICATIONS
maturation of terminal sprouts and less muscle fiber size discrep most likely because of the decreased life span of patients and ag
ancy, thereby leading to a decrease in the MUAPs' duration and gressive nature of ALS. It has been estimated that between 30
phasicity with a concomitant increase in amplitude. Initially, the and 50% of anterior horn cells can be lost without an appreciable
accumulation of immature collateral sprouts may result in some loss in strength secondary to the efficiency of collateral sprout
muscle fibers with tenuous electrical connections that fail during ing; however, these figures must be viewed with some reserva
continuous firing as a result of less than adequate acetylcholine tion because they are indirect means of assessment, but may
supplies. This leads to a variable number of muscle fibers per nevertheless be of some clinical use. 329,894 In some individuals,
motor unit per discharge, thus creating an unstable MUAP. following a rise in fiber density, this parameter can be observed
Observing the sequential firing of the MUAP over time results in to decline subsequently as patients become weaker, suggesting
the same MUAP having an increased variability regarding its failure of anterior horn cells to both maintain the increased
morphology changing in amplitude and possibly the number of number of muscle fibers per motor unit and/or continue to form
phases with each discharge. Over time, the MUAP stabilizes. It collateral sproutS. 802 About 90% of patients with various stages
is possible with rapidly progressive disease, or during the end of ALS demonstrate abnormal elevations in neuromuscular jitter
stage of the process, to observe short-duration low-amplitude po measurements. Jitter may be abnormal in persons with both pri
tentials appearing "myopathic" despite a reduced recruitment. marily upper or lower motor neuron symptoms and signs as well
This is likely a result of advanced disintegration of the motor as in muscles graded as normal on manual muscle testing, In
unit with profound loss of remaining viable anterior horn cells general, patients with significant lower motor neuron compared
and hence few muscle fibers still innervated. One can also ob with upper motor neuron signs have greater abnormalities on
served multiplet (doublets and triplets) MUAPs in some persons fiber density and jitter studies. Also, in persons with rapid dis
with ALS. A trigger and delay line will reveal some MUAPs ease progression, fiber density tends to be mildly to moderately
with late components or so-called satellite potentials.615 elevated, whereas jitter is significantly elevated. On the other
Advanced Needle Techniques. Single-fiber electromyo hand, pronounced increases in fiber density with only mild to
graphic examination in persons with ALS demonstrates a moderate increases in jitter values are found in patients with a
number of findings that provide insight into the disease's patho relatively slow disease progression.
physiology.730.782.783 ,785 Fiber density is increased 2-10 times Macro-electromyography recordings in patients with ALS
above the normal value of 1.5 in affected muscles (Fig, 16-15). reveal an increase in the potential's amplitude at times ap
The fiber density within the same patient can vary considerably proaching 20 times normal. 189,785,806 The dramatic increase in
from one muscle to the next and even be normal in some mus amplitude is found only in persons with increased fiber density
cles, whereas others demonstrate considerable abnormalities. An and mild to moderate increases in jitter, i.e., slowly progressive
increase in fiber density suggests that the process of collateral disease. This is compatible with the finding of increased fiber
sprouting in most patients with ALS is operational and contributes densities suggesting more muscle fibers per motor unit within a
significantly to motor unit remodeling. The increase in fiber den given territory, thus generating more voltage per unit region of
sity in ALS, however, does not approach the levels detected in muscle, hence an increase in amplitude. In other words, collat
more chronic disorders such as poliomyelitis or syringomyelia, eral sprouting results in more electrical activity per unit region
of muscle, thus accounting for an increase in both fiber density
and macro-electromyographic potential amplitude. Normal or
A B rarely reduced macro-electromyographic potential amplitudes
may be observed in patients with moderate increases in fiber
density, and markedly elevated jitter studies accompanied by
frequent blocking, i.e., rapidly progressive disease. Scanning
electromyographic recordings in patients with ALS demon
strates that the region of space or motor unit territory is essen
tially the same as that found in normal persons. This means that
although collateral sprouting may be significant, thereby adding
more muscle fibers per motor unit, the collateral sprouting is
confined to the original motor unit's spatial territory and does
not extend an appreciable distance across muscle fascicles.
Prognosis. Clinically, it stands to reason that older persons with
more severe disease have the worst prognosis of patients with ALS.
Treatment. There is no known cure for ALS, As noted
above, various forms of immunosuppression have been tried
without any noti'.ble efficacy.107,210,735,81O In addition, various
Figure '6-'5. Single-fiber recording from the tibialis ante forms of neurotrophic factors have been studied without defini
rior muscles in a patient with ALS. (A) Increased number of tive benefit. 56,84,462,552 Although a small trial of gabapentin ap
spikes within the 300 ~m recording territory of the Single-fiber elec peared promising,553 a larger double-blind, placebo-controlled
trode.Also, note neuromuscular blocking of individual spikes within trial failed to demonstrate any improvement. 554.
the complex as well as elevated jitter. (8) Similar increase in number Two controlled trials have demonstrated that riluzole extends
of spikes within a recording territory as well as increased jitter. Note tracheostomy-free survival by 2-3 months. 64 ,495 Riluzole is
that several spikes block simultaneously, indicating a block at a termi thought to act by inhibiting the release of glutamate at pre
nal nerve branch point, i.e., neurogenic blocking, (From Scllberg E, synaptic terminals,459 Unfortunately, the studies did not find that
Sanders DB:The motor unit inALS studies with different neurophysio riluzole improves strength or the quality of life. The recom
logical techniques, In Rose FC: Research Progress in Motor Neurone mended dose is 50 mg two times per day, Liver function tests
Disease. London, Pitman, 1984, pp 105-122, with permission.) need to be monitored because riluzole is hepatotoxic,
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 609
Supportive Care. Despite the lack of effective therapy to directly resulting from tumor invasion) is controversial.
halt or reverse progression of the disease, there are many thera Although not proven beyond question as arising from pure
peutic measures that improve the quality of life in ALS pa chance or the peculiarities of selected patient populations at
tients.480.554 We recommend a muItimodality approach in highly specialized referral centers, there does appear to be some
treating patients with motor neuron disease. We see patients at association between a few disorders of the motor neuron and
least every 3 months in conjunction with physical, occupational, neoplasms of the bronchial tree or reticuloendothelial system,
speech and respiratory therapy. We have patients evaluated by especially all types of lymphoma. One may consider four gen
psychiatry, gastroenterology, pulmonary medicine, and social eral categories of motor neuron syndromes associated with the
workers as necessary. remote effects of cancer: (I) typical ALS; (2) subacute motor
Spasticity. Spastic tone can be helped with baclofen, tizani neuronopathy in conjunction with lymphoma; (3) necrotizing
dine, benzodiazepines, or dantrolene. myelopathy; and (4) motor neuron disease as a component of
Dysphagia. Because of the associated swallowing difficul paraneoplastic encephalomyelitis.25.680.681 Those individuals with
ties occurring with bulbar weakness, nutrition becomes im clinically typical ALS who also have cancer are generally con
paired. High-calorie and protein-concentrated supplementation sidered by most clinicians to have developed these two diseases
should be added. 554 When dysphagia is severe, we recommend by chance with no direct causallink.94.694.907 Nevertheless, there
feeding through a percutaneous endoscopy gastrostomy (PEG). are a few patients reported to have improved neurologically or
Some studies have demonstrated that nutrition by PEG or gas stabilized following appropriate cancer treatment.118.241,556
trojejunostomy improves quality of life and survival by a few Almost 10% of patients with ALS have a monoclonal gam
months.263.511 However, other studies have not shown any signif mopathy suggesting a possible lymphoproliferative disease
icant benefit from PEG placement.I92.193 Ideally, PEG placement (LPD). In ALS patients with paraproteinemia, a skeletal survey
should be done before forced vital capacity falls below 50% in and bone marrow evaluation should be considered to evaluate
order to reduce the risks of the surgical procedure. Importantly, for plasmacytoma, myeloma, lymphoma, and other lymphopro
PEG placement does not prevent aspiration. liferative disorders. 499•696 The frequency of LPD in patients with
Dysarthria. We routinely have patients evaluated by speech MND has not been studied in a population or case-controlled
therapy. Patients may benefit from various speech augmentation analysis, but reportedly ranges from 2.5-5%.305 The most fre
devices, switch, or light-guided scanning computerized devices. quently associated LPD with motor neuropathy are Hodgkin's
Salivation. Drooling and hypersalivation can be a problem disease (HD) and non-Hodgkin's lymphoma (NHL), but chronic
secondary to swallowing difficulties. This can be treated with lymphocytic leukemia, Waldenstrom's macroglobulineia, multi
various anticholinergic medications. We often try an antidepres ple myeloma, and osteosclerotic myeloma have also been re
sant medication (e.g., amitryptiline) that has anticholinergic ported with MND.25,305,633.124,869
properties, and patients also not uncommonly have a reactive Subacute motor neuropathy was the earliest description of
depression. a motor neuropathy with LPD.633,724.864 This motor neuropathy
Constipation. Constipation may result from weakness of the can develop at any stage and can precede the diagnosis of a
pelvic and abdominal muscles, diminished physical activity, an LPD. Patients present with a subacute onset of painless asym
ticholinergic and anti spasticity medications, and opioids. metric weakness, usually initially involving the lower limbs,
Management includes increasing dietary fiber and fluid intake, along with widespread fasciculations and diminished or absent
adding bulk-forming laxatives, and the use of suppositories or reflexes. Some patients may have sensory symptoms, although
enemas as needed. there is a lack of object sensory signs. Initial reports commented
Ventilatory Failure. Most patients with ALS die secondary on the lack of corticospinal tract abnormalities. However,
to respiratory failure. It is important to assess for symptoms of Gordon et al. reviewed 26 patients with LPD and motor neuron
signs of respiratory impairment during each clinic visit. Patients disease, as well as 30 other cases reported in the literature. 305
with forced vital capacities below 50% or those with sympto While 25 of the 56 patients (45%) had a pure lower motor
matic respiratory dysfunction are offered non-invasive ventila neuron syndrome, 25 patients had definite upper motor neuron
tor support, usually BiPAP. We titrate the inspiratory and signs (Le., extensor plantar response or clonus) and 10 had
expiratory pressures to symptom relief and patient tolerability. probable upper motor neuron signs (Le., brisk reflexes in the
In our experience, only a few patients desire tracheostomy and presence of atrophic and weak limbs). CSF studies may reveal
mechanical ventilation, because they prolong expensive care an elevated protein, monoclonal spike, or oligoclonal bands.
and are often burdensome to the family; however, tracheostomy Nerve conduction studies demonstrate decreased amplitudes of
needs to be offered to patients along with realistic counseling in compound muscle action potentials and mild conduction veloc
regards to what this entails to the patient and the family. ity slowing. Needle EMG demonstrates evidence of active den
Pain. Pain occurs in at least 50% of patients as a result of ervation. Pathologic features include marked loss of motor
muscle cramps, spasticity, limited range of motion and contrac neurons in the cerebral cortex, brain stem, and spinal cord with
tures related to weakness, and skin pressure secondary to lim degeneration of the cortical spinal tracts and the ventral motor
ited movement. Careful positioning and repositioning of the roots. Interestingly, the course of the neuropathy appears inde
patient, physical therapy to help prevent contractures, antispas pendent of the activity of the underlying lymphoma. Although
ticity medications, antidepressants, non-steroidal anti-inflam there are reports of stabilization and improvement in motor
matory medications, and opioids may be used to treat pain. function a:fter successful treatment of the underlying malig
nancy, most patients (73%) continue to progress and die of the
Motor Neuron Syndrome Associated with the motor neuron disease. 305
Remote Effects of Cancer (Paraneoplastic One report suggested the possible association of breast
Motor Neuron Disorders) cancer with primary lateral sclerosis. However, 3 of the 5 pa
Clinical Features. The association between motor neuron tients eventually developed lower motor neuron findings, im
disease, particularly ALS, and the remote effects of cancer (not plying they actually had ALS, and they all continued to
610 - PART IV CLI NICAL APPLICATIONS
progress. 269 An idiopathic lumbosacral plexitis could not be ex I month-25 years) following the initial radiation dosage.
cluded on the clinical information reported. Thus, there is no Although each person has individual sensitivities, an upper limit
substantial evidence to suggest that any possible association be of radiation dosage in order to avoid spinal cord damage is be
tween motor neuron diseases and breast and renal cancers is lieved to be 6000 Rads administered over a period of 30-70 days
anything but coincidental. with a daily dosage not exceeding 200 Rads and less than 900
There are reports of anterior horn cell loss in patients with Rads per week.s
paraneoplastic encephalomyelitis/sensory neuronopathy as Acute transient radiation myelopathy is the most common
sociated with anti-Hu or ANNA-l antibodies.116.206.269.501.68o.681.&52 form of myelopathy associated with radiation therapy and pri
Anti-Hu antibodies are almost always seen in patients with small marily presents as paresthesias in the limbs induced by neck
cell lung cancer (SCLC), although other forms of malignancy flexion, i.e., Lhermitte's sign. It occurs most commonly with
have been described with this syndrome. The onset of symptoms cervical radiation, but may also be seen with treatment involv
can be acute or insidious and is frequently asymptomatic. The ing other regions of the spine. Aside from the paresthesias, there
neurologic disturbances often antedate the detection of the tumor are no other major complaints and the neurologic examination
by several months. Anti-Hu antibodies are usually evident in the is normal. After several months of these annoying sensations,
serum and CSF (sensitivity 88%, specificity 99%).560 Twenty to the problem dissipates without return. About 15% of patients
25% of patients with anti-Hu-related paraneoplastic syndromes undergoing some form of radiation affecting the spinal cord
have evidence of lower motor neuron weakness, although most may experience these symptoms. Chronic progressive radia
have an associated sensory neuronopathy or encephalomyelitis. tion myelitis begins with similar symptoms of Lhermitte's sign
Most patients continue to progress despite treatment of the un following radiation with an associated loss of pain and tempera
derlying cancer. Autopsy studies on three patients with promi ture perception. Over the ensuing months, all sensory modali
nent LMN involvement demonstrated severe loss of anterior ties as well as motor function become affected. The diagnosis of
horn cells, while the cortical spinal tracts appeared norma1.269.852 this form of radiation myelitis is primarily one of exclusion with
A variable degree of inflammation was evident in the spinal the following criteria generally required: (1) a history of radia
cord, dorsal root ganglia, and brain in two of the patients. tion involving the spinal cord; (2) neurologic deficits corre
Necrotizing myelopathy is a rare disorder primarily arising spond to the regions of spinal cord potentially irradiated; and
in conjunction with lung cancer or lymphoma. 591 The patient ex (3) a complete evaluation confirms the absence of recurrent
periences a rapid ascending paralysis resulting in flaccid para tumor or metastases to the spinal cord. The major form of
plegia with involvement of the sensory as well as motor system. pathologic involvement is that of a combination of primary radi
Bowel and bladder function are compromised. Unfortunately, ation-induced parenchymal and secondary vascular-induced
this disorder is fatal within weeks, usually as a result of pul spinal cord tissue damage. Acute quadriplegia/paraplegia
monary compromise. The etiology is unknown, and despite the secondary to radiation is very rare and results in a complete
rapid progression, a vascular etiology is unlikely based on sev neurologic deficit in hours to days. The cause of the type of ra
eral histopathologic examinations. diation syndrome is most likely a result of vascular damage with
Electrophysiologic Findings. In persons with atypical ALS, secondary spinal cord infarction.
the electrodiagnostic medicine evaluation is the same as that for A rare post-irradiation lumbosacral polyradiculopathy or
persons withALS not associated with cancer (see above).241.556,694 cauda equina syndrome, predilection for ventral roots, is well
The subacute motor neuronopathy disorder demonstrates elec characterized.69.88.248.278.706.818 For many years, the presumed
trophysiologic evidence of involvement of both the motor and locus of injury was the anterior horn cell and the entity was re
sensory systems. Specifically, the motor and sensory nerve con ferred to as a post-radiation motor neuron syndrome.106 Recent
duction studies may be normal, but more commonly demonstrate reports have convincingly demonstrated that the disorder is due
mild reductions in conduction velocity.724.864 In the few patients to predominant cauda equina damage. 88 •248 The radiation port in
reported, the motor and sensory CMAP and SNAP amplitudes cludes the TlO to L4 vertebral bodies and the inguinal region
wen,: not mentioned, Needle electromyographic examination, with most reported patients having received a total dose of more
however, demonstrates marked reductions in MUAP recruitment than 4000 cGy.88,509.706 Maier and coworkers suggested a toler
with variable alterations in MUAP amplitude and duration. ance limit of 1300 ret (-4000cGy over 28 days in 20 fractions),
Positive sharp waves and fibrillation potentials may be promi but cases have been reported with lower nominal standard dose
nent or sparse depending upon the muscle examined. (NSD).509
Electrodiagnostic medicine studies have not been detailed in The incidence of this disorder is 3-4%. The classic presenta
necrotizing myelopathy, but paraneoplastic encephalomyelitis tion is subacutely or chronically progressive pure motor, flaccid
can have reduced MUAP recruitment and occasional fibrillation paraparesis. The latency between radiation and onset of symp
potentials associated with borderline or normal nerve conduction toms varies widely, from 3 months to 25 years.88.509.81S Recent
velocities. 206 series have determined mean latencies of 5-6 years and a
median latency of -11 years. 88 Patients demonstrate a progres
TRAUMATIC OR TOXIC INJURIES AFFECTING sive loss of lower limb muscle mass occasionally accompanied
MOTOR NEURONS by fasciculation potentials with depressed or absent deep tendon
reflexes, and plantar responses are flexor. Sensation is normal,
Post-radiation Myelopathy/Motor Neuron Disease and sphincter function is usually preserved. The patient is left
with variable motor deficits depending upon the degree of
Clinical Features. There are four major categories of post-ra motor neurons affected. Rarely, the upper limbs may become
diation myelopathy: (1) an acute transient radiation myelopathy; involved; however, the lower limb presentation is typical for this
(2) a chronic progressive radiation myelitis; (3) an acute quadri disease even for patients receiving radiation to the cervical
plegia/paraplegia; and (4) a polyradiculopathy.88.299,400,605,607,660 In cord. 811 A focal insult to the spinal cord can result in a
general, all of these disorders can occur at variable periods (range monomelic amyotrophy presentation. 465
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 611
In most patients with this syndrome, the course is relentlessly (usually but not exclusively alternating current). Exposure to al
progressive. Some patients have stabilized after progressing for ternating current is typically more dangerous because of the
several months to 4 years. ss However, a number of them later re tetanic muscle effect usually induced by hand contraction re
sumed a deteriorating course after a 1-6 year delay. No treat sulting in difficulty releasing the offending current source, thus
ment is effective. causing longer current exposures and hence potentially more
Delayed, progressive, radiation-induced damage to the tissue damage. The energy content of a lightning bolt is consid
motor branches of cranial nerves V, VII, IX, XI, and XII can erably higher than human current sources and can reach up to
produce a syndrome resembling motor neuron disease. 296.641 100 million volts and between 100 and 200,000 amperes.
Accompanying long tract signs in 10% of patients-presum Exposure to direct lightning strikes, especially to the head, or
ably owing to a simultaneous brain stem encephalopathy-can high-tension currents can result in death if the current entering
masquerade as bulbar-onset ALS.474 Radiation-associated the body is of a sufficient intensity to result in cardiac dysfunc
cases are distinguished from ALS by the presence of tion, respiratory arrest, or direct cerebral insult. 610 Of note, when
myokymic and neuromyotonic discharges in involved muscles a patient is hit by lightning, the heart is usually depolarized en
(e.g., genioglossus, sternocleidomastoid, mentalis, masseter, masse and enters asystole with a subsequent spontaneous return
and trapezius).296.641 to a sinus rhythm. Alternating current exposure, however, can
Laboratory Features. MRI may demonstrate increased signal result in ventricular fibrillation. Other body tissues affected in
within the cervical cord in individuals with radiation-induced clude cataract formation (lightning), bony fractures or necrosis,
myelitis. Enhancement of the lumbosacral roots may be apparent muscle necrosis, tympanic membrane disruption, thermal burns
in patients with lower motor neuron disorder/polyradiculopathy. to the skin, and various neurologic insults. l64 Those persons who
Histopathology. Autopsy studies reveal changes suggestive survive the initial contact with the current source may experi
of a radiation-induced vasculopathy. Two postmortem examina ence a variety of neurologic problems that can be clinically di
tions showed axon loss, segmental demyelination, and fibrosis vided into immediate, intermediate, and delayed effects.754 Also,
of motor and sensory caudal nerve roots, with normal or chro the neurologic results of electric shock insult can be considered
matolyzed anterior horn cells. In one autopsy, there were ac from the perspective of cerebral, spinal, and peripheral nerve
companying signs of radiation vasculopathy,88 but vessels were syndromes. 245
normal in the other.70 A surgical specimen from one patient un The immediate effects of electric injury are primarily tran
dergoing lumbar laminectomy revealed intraspinal fibrosis. SIS A sient and localized primarily but not exclusively to the cerebral
sural nerve biopsy in one patient was normal.278 region with variable periods of loss of consciousness accompa
Electropbysiologic Findings. A number of electrodiagnos nied later by agitation, confusion, amnesia, and possibly
tic medicine evaluations are available for the lower motor seizures. 610 Those persons maintaining a relatively normal sen
neuron disease variety of the post-radiation syndromes. As sorium may experience severe pain at the locations of current
would be anticipated given the clinical findings, the electro entry and exit as well as along the internal current path; tinnitus
physiologic findings are consistent with primarily loss of the and deafness, particularly following a lightning blast; and visual
anterior horn cells. 278,367,449.465.706.81l The sensory nerve conduc blurring. Some persons may experience a number of motor ab
tion studies in the upper and lower limbs are normal commensu normalities including respiratory irregularity or paralysis, limb
rate with unremarkable sural nerve biopsies. Somatosensory weakness (occasional transient quadriplegia from hand-to-hand
evoked potentials reveal normal central conduction times and contact and hence current flow across the spinal cord), tremors,
cortical potentials. Similarly, motor nerve conduction studies and transient limb paralysis. Some persons may note transient
are also normal with the exception of reduced CMAP ampli limb paresthesias or hypesthesia. Obviously, thermal burns of
tudes to the affected regions. Needle electromyographic exami varying thickness are frequently experienced.
nation demonstrates reduced MUAP recruitment with increases Intermediate neurologic sequelae of electrical injuries are ar
in MUAP duration and amplitude as well as phases. Some pa bitrarily defined as occurring within the first 5 days of injury
tients may demonstrate fasciculation potentials. Positive sharp and usually resolve within a week of onset. 634 Muscular pain,
waves and fibrillation potentials are also noted in the affected headache, and transient limb paralysis extending from the im
regions, including the paraspinal muscles corresponding to the mediate time frame for about a week as previously noted are the
damaged spinal cord segments. primary findings in this time period. A number of neurologic
deficits may occur days to weeks and rarely years after the ini
Electrical/Lightning Strike Injuries tial electrical exposure. Cerebral effects include hemiplegia,
Clinical Features. Human contact with some form of in aphasia, seizures, and cerebellar dysfunction. The basal ganglia
tense electrical current such as lightning strikes, high-tension can be adversely affected with choreoathetosis and unilateral or
wires, or household sources (about one third of all deaths) re bilateral parkinsonian symptoms and signs becoming manifest.
sults in approximately 1000 deaths in the United States per The cranial nerves may be involved as demonstrated by loss of
year,l64.239,395a.610.754 With respect to electricity, it is important to taste, optic atrophy, auditory/vestibular dysfunction, and facial
note that death is primarily a result of how much current enters paresis. Brain stem insult may be manifested by facial hypes
the victim with current exposure described by Ohm's law, Le., thesia, dysphagia, tongue atrophy, and facial paralysis. Spinal
current (1) voltage (V) .;. resistance (R).610 In general, irrespec cord insult is relatively common, and focal or widespread de
tive of the voltage, the less current a patient is exposed to, the generation is possible with flaccid or spastic paraparesis or
less damage is incurred by various body tissues. A dry, cal quadriparesis/quadriplegia,148.363.482.766 A transverse myelitis,
loused hand, for example, offers considerably more resistance progressive motor neuron disorder, or ascending paralysis can
to current flow than a moist hand without callouses, thus result also be observed. Obvious peripheral nerve or plexus insults can
ing in less current flow in the former than the latter situation for occur, as current may traverse the peripheral nervous system for
equal amounts of voltage. Also, there is a difference between variable distances producing a mononeuropathy or multiple
lightning strikes (direct current) and human electric sources mononeuropathies. 239•796 Autonomic disturbances are relatively
612 - PART IV CLINICAL APPLICATIONS
common. Functional disturbances should not be minimized, and plantar flexors with plantar flexion, medial rotation, and inver
a post-traumatic psychoneurosis can develop. sion of the ankles. These spasms last about 15 minutes per bout.
Pertinent to this discussion is the development of a delayed Pain mayor may not accompany the muscle contractions. When
(weeks to months) but progressive spinal cord insult simulating present, the pain may be located not only in the plantar flexor
a motor neuron disorder similar to ALS.162 The clinical presen muscle group, but also in the major lower limb joints and low
tation may be that of an initial loss of muscle mass in the af back region. The muscle spasms are often precipitated by p~ys
fected limb occurring several months following an intense ical activity. Cold weather and rain have also been associated
electric shock. Over the ensuing months, the muscle mass loss with muscle spasm onset. Patients develop progressive diffi
progresses from the limb initially in contact with the current culty ambulating as a result of spasticity. The acute phase lasts
source to involve some or all of the remaining limbs. Upper about I month, after which time the patient is usually left with
motor neuron signs in the lower and possibly upper limbs permanent impairment. About 40% of patients present in a sub
appear with hypertonicity, hyperreflexia, extensor plantar re acute manner and reach the above-described level of impair
sponses, and sustained ankle clonus. These individuals may sta ment from 1 month to 1 year. An insidious onset is observed to
bilize or progress to death over the course of several months to occur in about 10% of patients with progressive loss of ambula
years. tion over the course of several years. Persons demonstrate gen
The immediate effects of electrical current contact are likely eralized hyperreflexia with the lower limbs affected to a greater
a result of thermal injury resulting from the conversion of elec degree than the upper limbs, and extensor plantar responses are
trical energy into thermal energy with a resultant heating of the observed.
neural structures in or about the path of current flow. The de The cremasteric and abdominal reflexes are commonly pre
layed effects of electrical insult are poorly understood and served. There is marked spasticity in the lower limbs with sus
appear quite similar to those induced by exposure to radiation. tained clonus at the ankles, increased tone, and a bilateral
It may be that the electrical currents or thermal insult induces a crossed adductor response. The upper limbs are relatively
delayed and slow endothelial fibrosis with secondary vascular spared, and bulbar symptoms are not usually noted. Urinary and
occlusion resulting in progressive ischemic insult to the mi anal sphincters are commonly spared, but impotence may be
crovasculature feeding the affected neural tissues. Alternatively, found in men. A few patients complain of paresthesias and lan
the electrical or thermal energy may adversely affect cellular cinating pains in the lower limbs for brief periods during the
DNA, eventually leading to neuronal cell dysfunction. 812 disease onset. Rarely, some persons develop significant muscle
Clearly, more data are required to fully understand the mecha wasting in the lower limbs. 6 The combination of upper and
nism of delayed neurologic insult. lower motor findings in these individuals suggests the possibil
Electrophysiologic Findings. The combination of relatively ity of ALS; otherwise, most persons appear to have a spastic
small numbers of electrical injuries and failure to obtain elec paraparesis. If the offending chick pea is no longer consumed
trodiagnostic consultations in these patients limits the electrodi prior to neurologic damage, the patient usually stabilizes; how
agnostic information available regarding this interesting insult ever, once the neurologic deficit is present, it usually remains.
to the nervous system. Those persons incurring peripheral nerve Histopathology. A few autopsies have demonstrated signifi
damage in the form of single or multiple mononeuropathies cant demyelination of the dorsal columns of the spinal cord and
demonstrate abnormalities localized to affected portions of the some degeneration of the anterior hom cells. 355 In addition,
peripheral nervous system.346.679.796 The primary insult is one of there are often eosinophilic inclusions within nerves.
axonal death resulting from thermal insult. Absent or reduced Electrophysiologic Findings. There is a distinct Jack of
amplitude CMAPs and SNAPs can be anticipated with accom electrodiagnostic medicine evaluations in these patients. The
panying reduced MUAP recruitment and positive sharp few patients that have been studied demonstrated normal motor
waves/fibrillation potentials. and sensory nerve conduction studies. 212 The only abnormality
In those persons with a delayed syndrome virtually identical noted is a mild reduction in the CMAP amplitude when
to ALS, expectant electrodiagnostic findings are noted.365.762 The recorded from the lower limb muscles. F-waves and H-reflexes
motor and sensory nerve conduction velocities are normal, as are also normal. There is a suggestion that some persons may
are the SNAP amplitudes. CMAP amplitudes are reduced in have mild electrophysiologic evidence of a peripheral neuropa
those regions with significant muscle wasting. It is possible for thy, but these studies require confirmation. Needle electromyo
F-wave latencies to be mildly prolonged. Needle electromyo graphic examination demonstrates positive sharp waves and
graphic examination reveals reduced MUAP recruitment ac fibrillation potentials in the lower limb muscles in several pa
companied by MUAPs with elevated amplitudes and long tients with and without evidence of gross muscle wasting. The
durations. Fasciculation potentials as well as positive sharp MUAPs demonstrate a reduced recruitment with a preponder
waves and fibrillations are noted in a widespread distribution. ance of large-amplitude long-duration polyphasic potentials.
Lathyrism MOTOR NEURON SYNDROMES SECONDARY
Clinical Features. Lathyrism is a rare disease of the motor TO INFECTION
system arising from ingestion of the toxin (~-N-oxalylamino-L
alanine: BOAA) contained in the grass or chick pea (Lathyrus Acute Poliomyelitis
sativus).321.502.555.645.778 The hardy chick pea is used as a food Clinical Features. Although poliomyelitis has been most
staple when other foods are not available. Lathyrism may mani frequently associated with poliomyelitis virus, it can be seen
fest at any age, but men are more commonly and severely af with other enteroviruses (e.g., coxsackievirus),5.647.695.865
fected than women. There are three modes of symptom onset: Poliovirus is a 300-angstrom icosahedron-shaped virus contain
(1) acute; (2) subacute; and (3) insidious. Approximately 50% ing a long single-stranded RNA core. There are three types of
of patients present with an acute form of lathyrism.ls4.ls5 poliomyelitis virus (types 1,2, and 3) distinguished by different
Patients present with an initial cramping or spasm of the foot antigenic aspects. The virus is worldwide in its distribution and
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 613
fortunately is not typically seen today. Because of this rarity, asymmetric. When the bulbar nuclei are involved, the IXth and
however, it is still important for physicians to recognize because Xth nuclei are the most commonly affected, with patients
patients may still be seen from time to time. particularly those demonstrating swallowing and phonation problems. The facial
individuals originating from underdeveloped regions. muscles may be affected, with some persons showing atrophy
The poliomyelitis virus gains access to its host through the of the tongue. Variable degrees of hypertension are commonly
oral route and undergoes rapid replication in the oropharynx seen in adult patients with hyperhidrosis or hypohidrosis of the
and distal gastrointestinal tract, as the virus is resistant to gastric affected body segment as well as shooting pains and paresthe
acidity. Once infected, the patient's mucosal and lymphatic tis sias in these regions. Constipation, gastric atony, and urinary re
sues serve as the region where the virus injects its RNA into the tention can also be experienced. A few unfortunate patients
cells and shuts the cells' metabolism down at the expense of cre progress to death over a relatively short period of time.
ating more virus particles, constituting the alimentary phase. The pattern of clinical involvement following the initial in
This process occurs in the cytoplasm, and a cell nucleus is not fection is a result of the anatomic arrangement of anterior hom
necessarily required. Within 24 hours, newly replicated virus cells within the spinal cord. SSI The vertical columns of anterior
particles are shed, and hence continued seeding into the gas hom cells supplying various muscle groups may lie in close
trointestinal tract from the oropharynx can continue for up to proximity to other anterior hom cells innervating muscles quite
3-4 weeks from the lymphatic tissue (lymphatic phase). displaced anatomically. Also, the lower limbs are more prone to
During this time frame, the patient can infect other individuals, complete paralysis secondary to the vertical columns of anterior
most commonly from the fecal-oral route and occasionally the hom cells extending over shorter distances, and hence more
oropharyngeal-oral route. Poor sanitary and crowded conditions likely to have all of the cells destroyed as opposed to the longer
thus predispose to the spread of this virus. From the mucosal re cervical segments.
gions and lymphatic tissues, the virus eventually gains access to Following the initial illness and paralysis, recovery of func
the blood stream (viremic phase). It is this viremic phase that tion to varying degrees occurs over the ensuing 4-8 years. The
correlates with the minor viral symptoms experienced by some initial functional recovery is considered too rapid to arise from
persons. With the virus spreading via the hematogenous route to axonal regrowth. Instead, functional return is considered to be a
other tissues, there is a continual buildup of virus within the result of (1) anterior hom cell recovery, and (2) collateral
body, and it can eventually gain access to the central nervous sprouting. It is known that not all of the anterior hom cells are
system. The exact mechanism is most likely through the blood destroyed by the polio virus, but instead a spectrum of dysfunc
stream, but some incorporation via the peripheral nervous tion occurs (Fig. 16-16). Some cells are completely destroyed,
system, possibly at the neuromuscular junction region, and sub others remain unaffected, and still others are in variable states
sequent transport to the anterior hom cell and thus the central of dysfunction. Some of the anterior hom cells in this latter cat
nervous system (axonal transport) may occur. Once in the cen egory go on to degenerate over time, while others regain a state
tral nervous system, the motor neurons of the spinal cord within capable of maintaining viable muscle fibers. All anterior horu
the lumbosacral and cervical enlargements and less so the tho cells not destroyed sprout collateral nerve fibers from their ter
racic region are the major targets; however, cells in the interme minal arborizations to reinnervate denervated muscle fibers. It
diolateral and posterior horns can also be affected with some is these processes that account for the clinical return noted in
extension into the dorsal root ganglion region. Areas in the brain patients.
and brain stem are also susceptible with nucleus ambiguus, Laboratory Features. CSF examination usually reveals in
facial, hypoglossal, and trigeminal motor nuclei particularly af creased protein and pleocytosis initially consisting of both poly
fected. A few regions in the precentral motor cortex, thalamus, morphonuclear leukocytes and lymphocytes and then later
and hypothalamus are also involved, as is the medulla's reticu predominantly lymphocytes. The cell count is usually less than
lar formation. There is an accompanying increase in CSF pro 100 cells/mm3 . Diagnosis may be confirmed by culture of the
tein and pleocytosis. offending virus, although the sensitivity is low. Also, acute and
The invasion of poliomyelitis virus leads to clinical symp convalescent antibody titers can be obtained.
toms and signs that are classified into two broad categories: (1) Electrophysiologic Findings. Sensory nerve conduction
minor illness, and (2) major illness. The majority of persons studies are essentially normal in poliomyelitis.403.767.843 CMAP
(98%), especially children, experience a minor nonspecific sys amplitudes may be reduced in patients with profound muscle at
temic illness. Some persons may describe a combination of all rophy. The motor conduction velocities and distal latencies may
or some of the following for 1-4 days: sore throat, vomiting, ab be slightly abnormal in those individuals consistent with the
dominal pain, low-grade fever, easy fatigue, and minor degree of large fiber loss. Repetitive stimulation studies can
headache. The preceding findings usually occur following an demonstrate a decrement during the convalescent stage of the
incubation period of 1-3 days and correspond to the above acute illness. 1I9
noted alimentary, lymphatic, and viremic phases. The needle electromyographic examination demonstrates a
A small percentage (2%) of those individuals with the minor reduction in MUAP recruitment in the affected spinal or bulbar
illness symptoms of headache, vomiting, fever, and malaise segments.353.638.767 These abnormalities are localized to those re
have an incubation period of 4-10 days, after which time neck gions affected by the virus. Additionally, positive sharp waves
and back stiffness are noted with easily arousable drowsiness. and fibrillation potentials can be anticipated to be present by
Some patients progress no further, whereas others develop mild 2-3 weeks following the onset of paralysis. Over the ensuing
hyperreflexia in the affected regions accompanied by some of years, these abnormal spontaneous potentials can still be de
the muscles demonstrating fasciculations. Soon thereafter, tected in the affected muscle groups but are of a sparse nature.
weakness manifests and the deep tendon reflexes become unob Also, their amplitude declines secondary to the denervated
tainable. As noted above, the affected segments are located pri muscle atrophying. The remaining MUAPs increase in duration,
marily in the lumbosacral region followed by the cervical region amplitude, and number of phases as a result of compensatory col
and, less commonly, the brain stem. The paralysis is typically lateral sprouting thus remodeling the motor unit. Fasciculation
614 - PART IV CLINICAL APPLICATIONS
potentials can be observed. Patients with poliomyelitis can have (2) residual muscular atrophy, weakness, and areflexia in an
MUAP amplitudes approaching and in some cases exceeding 10 asymmetric pattern in at least a single limb combined with
mV and even reaching 22 my'506 All of these changes can per nonnal sensation; (3) new onset of neuromuscular symptoms
sist indefinitely in the affected muscles. Of note, examination of such as musculoskeletal complaints, progressive muscle atro
persons years after the initial insult demonstrate abnormal phy, or both of the preceding; and (4) other possible etiologies
MUAP parameters in not only the clinically affected muscles, such as peripheral nerve compromise, orthopedic, medica.!, or
but also those believed to have been completely spared, suggest psychiatric dysfunctions have been excluded. 173 Possible risk
ing the disease process is much more widespread than initially factors predisposing individuals with a history of poliomyelitis
considered based on clinical examination alone. toward developing this syndrome include an initial severe loss
of muscle function, significant compromise of the bulbar and
Post·Poliomyelitis Syndrome respiratory muscles, and acquiring the disease at a relatively
Clinical Features. As many as 25-60% of patients with a older age. 7•174 There is no substantial clinical evidence to sug
history of poliomyelitis infection develop subsequent neuro gest that previous poliomyelitis predisposes individuals toward
muscular symptoms 20 or 30 years after the initial acute developing ALS.
attack. 140.152.312.325,41 1,656 Patients with post-polio syndrome com It is important to keep in mind that persons with so-called old
plain of progressive fatigue (80-90%), multiple joint pains polio have been functional at various levels for several decades
(70-87%), and muscle pain (70-85%), They may experience utilizing weak muscles, transplanted muscles secondary to surgi
decreased mobility arising from scoliosis or altered body bio cal procedures, nonnal muscles in substitution patterns, and em
mechanics and posture, or physical decompensation following a ploying compensatory joint movement against gravity in order to
recent weight gain or brief period of immobility secondary to maintain function and perfonn activities of daily living. All of
some fonn of physical trauma. These symptoms may be rather these factors are likely to predispose these individuals to exces
vague and nonspecific, with occasional accompanying emo sive joint wear-and-tear, developing entrapment neuropathies
tional upset. Some 50-80% of patients also develop progressive from using ambulatory aids (e.g., carpal tunnel syndrome, ulnar
loss of strength and muscle atrophy} 19.172,312 This progressive neuropathies at the wrist or elbow), and incurring plexopathies
weakness usually involves previously affected muscles, but or radiculopathies. All of these findings are to be expected as a
muscles thought to be clinically spared at the time of the acute consequence of years of poor posture and biomechanical
infection may at times become affected. 9•324,879 Muscle pain, malalignment but are not considered part of the post-po
cramps, and fasciculations are also commonly noted. In individ liomyelitis syndrome. The above joint and neuromusculoskeletal
uals with previous bulbar and respiratory problems, there may problems should be dealt with expeditiously so as to maintain
be an increase in difficulty swallowing or breathing with some the patient's independence.
ventilatory support required, especially at night. Rarely, sleep Laboratory Features. Unlike acute poliomyelitis, the CSF
apnea may become apparent, which is likely a result of an exac does not demonstrate pleocytosis. There is no evidence of
erbation of the original insult to the brain stem reticular fonna active infection. Serum creatine kinase levels may be mildly
tion, obstruction secondary to pharyngeal weakness, reduced elevated.580.866
respiratory muscle function, or a combination of all or some of Histopathology. Muscle biopsies demonstrate grouped atro
the above. Fortunately, the loss of muscle function is rather slow phy and fiber type grouping. 173•312
over the course of many years.s Pathogenesis. The exact etiology of post-polio syndrome is
The diagnosis of post-poliomyelitis syndrome is made by sat not well established; however, a popular theory considers the
isfying the following criteria: (1) previous history consistent initial disease insult from the perspective of motor neuron
with poliomyelitis and functional stability for at least 15 years; damage and hence residual functioning of the remaining anterior
1. Normal (non-stressed) 2. Nomal, previously unaffected, Figure 16-16. Schematic representation of the conse
but now stressed quences of poliomyelitis on the affected motor neuron pool.
( I ) There are no doubt some motor neurons that escape damage,
as do their neighbors, and are not called upon to remodel neigh
boring motor units. (2) Some motor neurons may not have been
affected by the disease process, but are next to those motor neu
rons that have.As a result, the intact motor neuron is called upon
to form collateral sprouts within the affected muscle tissue and
support considerably more muscle fibers than prior to the disease
insult. (3) A population of motor neurons may have been partially
affected by the poliomyelitis virus but survived somewhat "dam
aged" but still capable of supporting muscle fibers. It is likely that
3. "Nonnar -looking, fully recovered 4. "Seane", incompletely recovered,
some of their neighbors may not have survived, with the remain
but smaller In size; overstressed overstressed
ing compromised motor neuron having the responsibility of collat
eral sprouting. thereby potentially creating a double streSs for this
particular anterior horn cell population. (4) A number of motor
neurons are simply damaged beyond recovery and die. leaving all
of their muscle fibers denervated, hopefully to be reinnervated by
intact anterior horn cells. (From Dalakas M, ilia I: Post-poliO syn
drome: Concepts in clinical diagnosis, pathogenesis, and etiology.
Adv Neurol 1991 ;56:495-511. with permission.)
Chapter 16 DISORDERSAFFECTING MOTOR NEURONS - 615
Figure , 6-17. Postulated mechanism of how patients with poliomyelitis experience new onset weakness or the so-called post-po
liomyelitis progressive muscular atrophy (PPMA). Prior to the viral attack, there are a "norma'" number of muscle fibers innervated by each motor
neuron (Normal). Secondary to the acute poliomyelitis, some motor neurons die, others remain unaffected, while still other are somewhat dys.
functional but eventually survive (Acute Pollo).The remaining motor neurons then form collateral sprouts to reinnervate the denervated muscle
fibers, thus increasing their metabolic demand to maintain an increased number of muscle fibers (Recovery and Continuous Remodeling).
This process continues depending upon how many motor neurons are left and the state of their metabolism. After 30 years, it is conceivable that
the motor neuron's metabolism begins to be overstressed. with the partially compromised motor neurons failing first (PPMA).An increasing
demand is made on the remaining motor neurons through collateral sprouting, eventually leading to significant metabolic stress and progressive
failure of newly form collateral sprouts and at time loss of entire motor neurons. (From Dalakas M, lila I: Post-polio syndrome: Concepts in clinical
diagnosis, pathogenesis, and etiology.Adv Neurol 1991 ;56:495-511, with permission.)
hom cells noted above (Fig. 16-16)Y4 Four subpopulations of persons with post-poliomyelitis syndrome. These abnormalities
motor neurons are postulated to result following the initial acute are not likely a result of the poliomyelitis but more so a conse
poliomyelitis insult. Specifically, some motor neurons may quence of compensatory living skills predisposing these persons
remain unaffected to experience no change, whereas other to the above-noted overuse compression or entrapment neu
normal motor neurons form extensive collateral sprouts to rein ropathies. Finding an abnormal sensory response in a patient
nervate those muscle fibers rendered denervated as a result of with post-poliomyelitis syndrome should prompt a search for
the anterior hom cells that died. A fourth type of motor neuron some type of peripheral nerve disorder.
involves those that were only partially affected but survived the Motor nerve conduction velocities can be anticipated to be
attack. The normal and disease-stressed anterior hom cells may normal in most persons if a CMAP can be obtained, i.e., signifi
then be called upon to form multiple collateral sprouts (Fig. 16 cant muscle atrophy is not present.81.126.256.892 Considerable loss
17). This increase in collateral sprouting means that both the of muscle bulk is usually accompanied by an absent or very
normal and "sick" motor neurons have a profound increase in small CMAP, in which case the nerve conduction velocity is
metabolic demand placed on them. It is postulated that this either unobtainable or unreliable. Similar statements can be
metabolic stress on both normal and "sick" motor neurons can made regarding F-waves. Prolongations in distal motor laten
only go on for so long prior to reducing the anterior hom cell's cies again should raise the suspicion of possible entrapment
ability to continually support all of its excess muscle fibers. neuropathies or a more generalized peripheral neuropathy unre
This results in an increasing population of denervated muscle lated to the poliomyelitis. Repetitive stimulation of various
fibers being created with some, but either short-lived or ineffec nerves innervating clinically affected as well as nonaffected
tive, reinnervation through newly form collateral sprouts. At muscle groups do not show a decrement at low or high rates of
some point, when the motor neurons' reserve is exhausted, the repetitive stimulation. 256
process of collateral sprouting is no longer effective and the pa Needle electromyographic evaluation in patients with post
tient begins to experience this motor neuron metabolic collapse polio syndrome is indistinguishable from those persons who
as new-onset weakness. The muscle biopsy supports these as had poliomyelitis of similar degree years ago but with no new
sertions, with variable degrees of neurogenic group atrophy plus physical complaints. The clinically affected muscles clearly
findings suggestive of "myopathic" features of connective tissue demonstrate a marked reduction in MUAP recruitment often ac
proliferation, necrotic tissue with phagocytosis, fiber size varia companied by MUAPs with abnormal parameters. 1OO•506
tion, fiber splitting, and internal nuclei. Specifically, the majority of MUAPs are increased in amplitude,
Electropbysiologic Findings. Sensory nerve conduction even approaching 20-30 mV. MUAP duration is prolonged, and
studies demonstrate normal SNAP parameters. 115,256,892 If the there is an increase in the number of polyphasic MUAPs. Fas
median or ulnar nerves are exclusively examined, slight reduc ciculation potentials may be seen in some patients and can be
tions in amplitude and occasional absent responses combined quite prominent at times. 256 Positive sharp waves and fibrillation
with variable latency prolongations may be detected in some potentials may be noted in weak as well as in clinically uninvolved
616 - PART IV CLINICAL APPLICATIONS
Iimbs.100.135,172.432.516.566.580.877 Individuals with the post-polio syn with old poliomyelitis irrespective of symptoms. In brief, there
drome may have greater degrees of fibrillation potentials in are no distinguishing electrophysiologic characteristics between
muscles with new-onset weakness. However, this is not of help those persons with stable old poliomyelitis and individuals with
because some persons with prior poliomyelitis but without new symptoms and signs consistent with post-poliomyelitis syn
weakness can have easily detectable fibrillation potentials many drome. 658 The post-poliomyelitis syndrome is, therefore, primar
years after the acute infection.43.101.58o Perhaps the most interest ily a clinical diagnosis not capable of being distinguished
ing finding in patients with old poliomyelitis with or without through electrodiagnostic medicine techniques.
new symptoms is the documentation of abnormal MUAP re Treatment. There are no specific therapies for post-polio
cruitment as well as increases in MUAP duration, amplitUde, syndrome. A recent double-blind, placebo-controlled trial
and number of phases in muscle groups not believed to have demonstrated no benefit with pyridostigmine. 835 Patients may
been involved in the original disease process, i.e., muscle with benefit from physical and occupational therapy as well as other
normal bulk and strength. 168.348.365.892 This finding suggests that supportive measures. 823 Muscle pain may ease with tricyclic an
the original disease process is more widespread than suspected tidepressant medications. Severe dysphagia, dysarthria, and res
clinically at the time of the acute attack, with subsequent motor piratory weakness are treated as discussed in the ALS section.
unit remodeling and compensation.
Single-fiber electromyographic analysis of patients with the Retroviral-Associated Motor Neuron Disease
post-poliomyelitis syndrome demonstrates an increase in jitter The retroviruses consist of the lentiviruses (e.g., HIV: AIDS)
and fiber density as well as neuromuscular blocking, as would and oncomaviruses (HTLV-I: e.g., tropical spastic paraparesis).
be anticipated given the basic pathophysiology of denervation A few reports of motor neuron or motor neuron-like disorders
and compensatory reinnervation. 100.236.312.705 Because the jitter have been reported with these viruses. The small number of pa
continues to be significantly elevated as opposed to decreasing tient reports suggests at this point that there is some association
over time, one must conclude that there is ongoing denervation between the virus and neurologic dysfunction, but further stud
and reinnervation maintaining excessively elevated jitter values ies are required to better define this relationship.
supporting the above postulates. 223 The jitter and fiber density
may be slightly increased in patients with the post-poliomyelitis Human Immunodeficiency Virus (Acquired Immune
syndrome compared with those persons with old poliomyelitis Deficiency Syndrome: AIDS)
but no new symptoms; however, these distinctions cannot be The association between AIDS and various peripheral ner
made on an individual patient basis. In the few patients followed vous system manifestations of the disease is clearly estab
with electrophysioIogic studies over the course of many years, lished. 67.55 1,613 However, there are only rare reports of motor
the jitter appears to increase with time. Also, in muscles with neuron disease in patients with HIV infection.362.758.853 Elec
profound muscle loss where there are more denervated muscle trodiagnostic medicine evaluations revealed nerve conduction
fibers than could be reinnervated, the MUAP remains unstable studies and needle electromyographic evaluation consistent
(variable morphology with each discharge), suggesting an on with motor neuron disease. All persons demonstrated continu
going process of denervation and reinnervation as proposed ous progression of the disease despite a transient stabilization
above.877.880 following a course of intravenous immunoglobulin in one
The MUAPs as recorded with macro-EMG demonstrate large person.
potentials with a mean of 7.5 times, and rarely, reaching 35
times normal, consistent with significant increases in the HTLV-I: Tropical Spastic Paraparesis
number of muscle fibers per motor unit. 223.3 12,588,787.878 A few in There is a clear association between HTLV-I and tropical
vestigators have documented a reduction in macro-MUAP am spastic paraparesis, with up to 68% of patients demonstrating
plitudes with disease progression, suggesting that the motor unit antibodies to the virus, thus having an HTLV-I-related
initially forms successful collateral sprouts (large macro myelopathy (also known as HAM) as well as occasional associ
MUAPs) but then over time the anterior hom cell can no longer ated peripheral neuropathy and myositis. 75 ,198 Tropical spastic
sustain all of the muscle fibers, with a resultant decline in the paraparesis is endemic to many tropical and subtropical coun
macro-MUAP.467 This finding again supports the above postu tries. There are abnormalities of somatosensory evoked poten
late regarding a gradual metabolic decline in the remaining an tials consistent with a myelopathy as well as frequent alterations
terior hom cells and may be of benefit in detecting andlor of the visual and brain stem auditory evoked potential stud
documenting those persons with postpolio muscle atrophy ies.38.166.418,503 Rare cases have been reported to have seropositiv
(PPMA); however, long-term serial studies are necessary.1I9 ity for this virus with clinical symptoms and signs of motor
This is of limited value in persons who present with supposed neuron disease. 431 One patient with HTLV-I infection presented
new-onset weakness, as there is no previous documentation of with a clinical and electrodiagnostic picture suggestive of motor
macro-MUAP values. neuron disease !Jut instead had a combination of chronic
When all of the electrophysiologic data are collated between polymyositis and myelopathy.240 This combination of diseases
persons suffering from post-polio syndrome and those with old should be kept in mind as presenting similarly to ALS. Large
poliomyelitis but no new symptoms, a number of findings are of amplitude MUAPs with positive sharp waves and fibrillation
interest. 81 ,135 The motor and sensory nerve conduction studies are potentials can be detected in chronic polymyositis. The nerve
normal in both groups. Needle electromyography, quantitative conduction studies, motor and sensory, are normal, thus sug
and routine, demonstrates equal reductions in MUAP recruit gesting ALS when the electrophysiologic findings are combined
ment and increases in MUAP duration, amplitude, and phases. with upper motor neuron signs secondary to the myelopathy.
Single-fiber electromyographic studies find equally elevated
jitter and neuromuscular blocking as well as increased fiber den Syphilis/Neurosyphilis
sity values for both patient populations. Macro-electromyogra Clinical Features. Syphilis is caused by an infection with the
phy similarly reveals large amplitUde MUAPs for all persons spirochete organism called Treponema pallidum. 244,369,731.749,895
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 617
This organism is quite small (6-15Ilm long by 0.151lm wide) neurosyphilis where the only abnormalities are a positive CSF
and is not directly visible with light microscopy, but it can best VDRL and CSF pleocytosis with elevated protein levels as well
be viewed by darkfield microscopic techniques. The most as the expected positive serum FfA-ABS test. For a variable
common method of transmission is through some form of period up to and exceeding 30-40 years after the initial expo
sexual intimacy where the host acquires the organism through sure, untreated patients can go on to experience a whole host of
skin contact (usually sexual organs, oral cavity, or skin lesions) seemingly unrelated symptoms secondary to the fifth stage or
with the infected person. It is also possible for intravenous drug symptomatic tertiary syphilis, which is only infectious to the
users to share needles with infected persons and acquire the dis fetus as passed on by the mother. The basic pathology in tertiary
ease in this manner. The spirochete is rather fastidious and is syphilis is the development of a diffuse vascular inflammatory
not readily cultured, requiring direct visualization or serologic disease (obliterative endarteritis) with the formation of gummas
testing in order to make a definitive diagnosis. Depending on (coagulative necrosis with surrounding lymphocytes and
the individual patient's predisposition toward the disease and mononuclear cells) throughout the body. Although gummas
time of examination from first infection (illness duration), the commonly involve the skin, it is possible for bone, liver, gas
clinical manifestations of syphilis can be quite varied, earning trointestinal, and lung tissues to also be involved. If a gumma de
the title, "Syphilis: The Great Imitator." velops in a vital location of the liver, heart, or brain, death may
The exact incidence of syphilis is unknown, most likely because ensue. Syphilis can result in cardiac disease with an aneurysm of
of under-reporting, but has recently been estimated to approximate the ascending aorta, valvular insufficiency, and dysfunction of
18.41100,000 population. This figure represents an alarming and the coronary arteries. Neurosyphilis may develop in about 20%
dramatic increase over the past several years. The true reason for of patients with untreated syphilis by about 10 years following
this increase is not fully known, but may be a result of increasing the initial inoculation.
drug and sexual promiscuity combined with a reduced public Neurosyphilis may be present in one of four forms: (1)
health awareness of the disease secondary to effective treatment. asymptomatic, (2) meningovascular syphilis, (3) general pare
Individuals with HIV infection have a higher incidence of syphilis, sis, and (4) tabes dorsalis. 123,335.364,409.675.751,756.757,851.865 As noted
and it may manifest in a more aggressive manner in these persons above, the asymptomatic form of neurosyphilis is characterized
particularly when immunocomprornised.68•69•402,427.717 by an elevated CSF protein « 100 mg/dl) with a relatively low
There are five recognized clinical stages of the disease: (1) cell count « 100 lymphocytes/mm3). Meningovascular neu
primary syphilis; (2) secondary syphilis; (3) latent syphilis; (4) rosyphilis usually, although not always, occurs within about 1
tertiary (late) asymptomatic syphilis; and (5) tertiary (late) year of the initial inoculation. The clinical appearance can be
symptomatic syphilis. The first stage of the illness (primary quite similar to aseptic meningitis as manifested by headache,
syphilitic stage) is signified by the development of a skin lesion stiff neck, fever, and photophobia. More serious consequences
(chancre) at the site of primary infection within 10-90 (mean include single or multiple cranial nerve palsies (essentially any
21) days following inoculation. The chancre is typically but not cranial nerve can be involved), hydrocephalus, or even stroke.
always a solitary lesion. In the genital region, it is usually a pain The CSF and serum are positive for T. pallidum infection.
less indurated nodule with raised borders. Extragenital lesions General paresis usually manifests rather late, 10-20 years, fol
(lips, tongue, oral mucosa, anus, nipples, fingers), however, tend lowing the initial infection and has a gradual loss of higher
to be painful. The chancre commonly heals spontaneously in mental functions (impaired memory, irritability, headache,
several weeks following its appearance. By about 4 weeks, the altered personality), associated increases in confusion, and pos
lymph nodes draining the infected regions can become enlarged, sibly generalized paresis late in the disease, Le., a meningoen
firm, and painless. During this first stage of the disease, the pa cephalitis. Subtle or overt psychotic symptoms are usually
tient's chancre, blood. and lymph nodes are highly infectious. associated with the progressive loss of mental function. Tabes
The second stage (secondary syphilis) of the disease begins dorsalis is associated with progressive destruction of the poste
within a few weeks to months (6-20 weeks) after the chancre's rior columns and dorsal root regions proximal to the dorsal root
development. Essentially any aspect of the patient's skin or ganglion area. A classic triad of symptoms (lightning pains in
mucosa can become involved. The most common presentation is the limbs, dysuria, and ataxia) and signs (Argyll-Robertson
of a dry, non pruritic skin lesion resembling a maculopapular pupils, areflexia, and loss of proprioception in the lower limbs)
rash. A particularly common location for this lesion is the soles can be found in individuals with tabes dorsalis. These so-called
of the feet and palms of the hands, with the face typically spared. classic findings are not always present, however, and persons
Where moist body surfaces juxtapose (axilla and inguinaUper may present with varied symptoms and signs. Patients usually
ineal areas), the skin papules fuse to form the very infectious demonstrate a reduction in position sense, vibration, sensory
condylomata. A low-grade fever, malaise, sore throat, headache, ataxia, and reflexes, i.e., posterior column and dorsal root func
lymphadenopathy, and some loss of hair (eyelashes and lateral tion. Associated Charcot joints. impotence, and urinary inconti
third of the eyebrows) may also be seen. A diffuse form of pain nence can be detected in some persons. Some persons may
affecting the long bones and skull may be noted as well as he demonstrate the so-called Argyll-Robertson pupil, i.e., the pupil
patitis without jaundice. The third stage (latent syphilis) is char accommodates but fails to react to light.
acterized by a complete lack of any symptoms and can last for A number of additional neurologic manifestations may be
about 1 year following resolution of the second stage's dermato noted in patients with neurosyphilis. The disease may spread
logic signs. The only way of making the diagnosis at this time is from the posterior root to also involve the ventral root and
through positive serologic studies. This stage of the disease is of result in a radiculitis with patients presenting with a radicu
a very low infectious nature, but pregnant women can pass on lopathy in the cervical, thoracic, or lumbosacral regions. The
the disease to their children producing congenital syphilis. The obliterative endarteritis can produce an occlusion of a spinal
fourth stage or tertiary stage of the disease is the primary cause artery with an ensuing transverse myelopathy and quadripare
of morbidity in adult patients. By about 4 years, a number of per sis/plegia or paraparesis/plegia. Similar symptoms may result
sons with untreated syphilis may demonstrate asymptomatic from an inflammatory meningitis with spinal cord compression.
618 - PART IV CLINICAL APPLICATIONS
Some persons may present with a clinical picture identical to The motor conduction studies also demonstrate normal distal
acute inflammatory po!yradiculoneuropathy, Le., Guillain motor latencies, CMAP amplitudes, nerve conduction velocities,
Barre syndrome. and F-waves. Of note, tibial nerve H-reflexes are absent. This is
In children born to mothers infected with the spirochete, con understandable, given that tabetic neurosyphilis affects not only
genital syphilis can develop as a result of transplacental transfer the posterior column fibers, but also the dorsal roots themselves
of T. pallidum usually after the 18th week of gestation. proximal to the dorsal root ganglion (see above). Because the, af
Congenital syphilis can present clinically within the first month ferent impulse is prevented from entering the spinal cord, the H
or up to 1 year of age and resembles secondary syphilis. A sig reflex pathway is interrupted. thus precluding the efferent
nificant nasal discharge is usually present secondary to nasal pathway from being activated. The needle electromyographic ex
mucosa involvement. The dermal and mucosal lesions are amination is reported to demonstrate a few positive sharp waves
highly infective. The CSF may be abnormal and accompany he and fibrillation potentials in the gastrocnemius muscles bilater
patosplenomegaly, hemolytic anemia, and painful osteochondri ally. This finding may be postulated to occur as a result of some
tis. If untreated for 2 or more years, patients develop inflammation of the syphilitic infection spreading from the
wide-spaced indented teeth (Hutchinson's teeth), frontal boss dorsal to ventral root regions in the S I region. Persons with
ing, saddle nose, maxillary deformation, and bowing of the AIDP or polyradiculopathies can be expected to demonstrate
tibias (so-called saber shins). The disease may preferentially nerve conduction and needle electromyographic abnormalities
injure the eighth nerve. consistent with the appropriate disease entity.
The drug of choice for all stages of the disease is high-dose
penicillin. The reason so much emphasis is placed on this dis Subacute Spongiform Encephalopathy
ease in a textbook on electrodiagnostic medicine is severalfold. (Creutzfeldt-Jakob Disease)
First is the myriad of presentation with which patients with var Clinical Features. Subacute spongiform encephalopathy,
ious forms of syphilis may be referred for an electrodiagnostic also called Creutzfeldt-Jakob disease (CJD), can be inherited or
medicine consultation. Although the electrodiagnostic tests are more commonly is transmitted by an abnormal prion pro
relatively normal, a high index of suspicion can lead to appro tein. 5 ,520,612.695.711.897 The annual incidence is approximately
priate tests to confirm the clinical impression. Second, the rela 1-2/million population per year. A family history is found in
tive rarity yet increasing frequency of this disease results in it about 4-8% of patients owing to a mutation in the prion protein
frequently being left out of the differential diagnosis for many gene on chromosome 20p.297 Men and women are affected
diseases in which it should be included. Keeping this disease in equally with a mean onset age of 61.5 years (19-83 years).l04
mind may help the referring physician more efficiently arrive at About one third of patients note the disease beginning with
the most appropriate diagnosis. Third, the prompt recognition vague prodromal symptoms of fatigue, altered and disturbed
and treatment with penicillin during an early phase of the dis sleeping patterns, and reduced appetite a few weeks prior to the
ease can lead to resolution of the disease and spare the patient disease's neurologic manifestations. In roughly 20% of patients,
multiple disorders associated with an increasing morbidity the the neurologic symptoms begin abruptly without a gradual shift
longer the patient goes undiagnosed. of prodrome to neurologic problems. Approximately two-thirds
Electrophysiologic Findings. The location of the syphilitic of patients experience some type of mental deterioration in the
lesion dictates not only the patient's symptoms and signs, but also form of dementia, behavioral abnormalities, or reduced higher
the electrodiagnostic findings. Unfortunately, there have been ac cortical function as the earliest neurologic symptom. A third of
counts of electrodiagnostic medicine evaluations in only 1 or 2 patients note the onset of the disease as involving gait distur
patients. The above emphasis on syphilis will, it is hoped, prompt bances (cerebellar) or reduced visual ability (loss of vision, ab
further investigations and reports into this interesting disease. normal color perception, or diplopia) with lower limb weakness
When strokes occur as a result of neurosyphilitic infections, and spasticity. At some time during the course of the disease,
the routine peripheral nerve conduction studies can be antici usually in the terminal aspects, other abnormalities can become
pated to remain normal. A loss of a cortical SEP response may prominent: movement disorders (e.g., myoclonus, athetosis,
occur if the lesion is large enough to damage a portion of the chorea), headache, vertigo, distal limb paresthesias, extrapyra
cerebral somatosensory cortex or interrupt the central conduct midal muscular rigidity in the form of "lead-pipe rigidity," all
ing pathway. If the facial nerve is affected, a reduced CMAP forms of seizures, and lower motor neuron signs of muscular at
amplitude associated with reduced voluntary MUAPs and ab rophy, fasciculations, and muscle wasting with depressed deep
normal spontaneous potentials (positive sharp waves and fibril tendon reflexes.
lation potentials) can be expected. SSt Approximately 11 % of patients with CJD have LMN involve
Individuals with tabes dorsalis are perhaps the most likely pa ment. Rarely, the amyotrophy is the presenting feature of the
tients with neurosyphilis to be referred for an electrodiagnostic disorder. 19.897 In all forms of the disease, however, the mental
medicine consultation. 205 This is anticipated because of the disturbances soon dominate the clinical presentation, minimiz
symptoms suggestive of a sensory peripheral neuropathy, i.e., ing any confusion with pure motor neuron disease. These find
loss of reflexes, proprioception, and vibration. The sensory ings suggest that the amyotrophic form of CJD may be much
studies reveal normal SNAPs in the upper and lower limbs with more common than initially believed. Unfortunately, the disease
respect to all measured parameters. Somatosensory evoked po is rapidly progressive, often with demonstrable clinical changes
tentials of the median nerve were normal in the single patient from one day to the next. About 90% of patients die within 1
studied; however, the tibial nerve SEPs were abnormal, consistent year of diagnosis, with a median illness duration of 4 months.
with a lesion affecting the posterior columns below the cervical Persons examined with the amyotrophic form of the disease
region. 199 Visual evoked potentials have been demonstrated to have a considerably longer disease course.
be abnormal in 50% of patients with tabes dorsalis, 18% of per Laboratory Features. CSF examination reveals a positive
sons with general paresis, and 13% of individuals with immunoassay for the 14-3-3 protein, which has high sensitivity
meningovascular neurosyphilis. 159 and specificity of CJD.
Chapter 16 DISORDERSAFFECTING MOTOR NEURONS - 619
prolongation accompanied by giant (10-40 mV) cortical poten Spinal anesthesia Multiple sclerosis
tialS. 1O,11,125,222,435,742 Most patients with amyotrophy have essentially Chemotherapy Lupus angiitis
loss, and parenchymal necrosis extending asymmetrically and detected in the thoracic region. Nuchal rigidity and fever may
for variable distances depending upon the extent of the radiation be noted in about half of examined patients. Resolution of
field. The insult to tracts and more importantly cell bodies can symptoms is variable and dependent on the degree of tissue
result in widespread degeneration of various spinal tracts. insult. Magnetic resonance imaging can be of considerable as
Symptoms and signs or radiation spinal cord damage may pre sistance in defining the location of the lesion as well as the eti
sent in one of four ways: (l) transient sensory symptoms that ology in many cases. 45.434 •
occur about 4 months after radiation resembling Lhermitte's sign Electrophysiologic Findings. The electrophysiologic find
and that may last for several weeks to 9 months; (2) slowly pro ings in patients with a cervical myelopathy or myelitis is directly
gressive myelopathy occurring between 3 months to 5 years after dependent on both the degree of spinal cord insult and lesion lo
the radiation manifesting initially as lower limb paresthesias and cation with respect to specific neural pathways and cell bodies.
unfortunately progressing to paraparesis/quadriparesis or a One of the more common and hence better electrodiagnostically
Brown-Sequard pattern with death resulting in months to several investigated myelopathies is that arising from cervical spondylo
years; (3) a so-called amyotrophic pattern associated with pri sis. The electrodiagnostic evidence available is presented with
marily but not exclusively anterior hom cell loss; and (4) acute additional information from other disorders as they pertain to the
transverse myelopathy. The first two patterns of clinical presen specific findings not mentioned in the remainder of this chapter.
tation are the most commonly encountered. High-voltage and In cervical spondylotic myelopathy, both the spinal cord sub
current electricity exposure usually occurs through contact with stance and nerve roots may be affected to varying degrees.
both hands, thus resulting in cervical spinal cord damage as the Because the offending compressive lesion is most commonly
current passes between the hands. Multiple parenchymal hemor located proximal to the dorsal root ganglion, the routine periph
rhages with eventual development of myelomalacia can occur eral sensory nerve conduction techniques are normal, i.e.,
with varying degrees of clinical symptoms depending upon the SNAP sensory latency, conduction velocity, and amplitude. Of
amount of current and hence tissue damage. Decompression interest is a single report documenting 12 of 16 patients with
sickness, also known as dysbarism, results from rapid alter cervical myelopathy having normal SNAP studies with the ex
ations in atmospheric pressures (e.g., underwater divers) with the ception of abnormally (> 2 standard deviations) large SNAP
formation of gas bubbles exiting tissues too rapidly, potentially amplitudes. 651 The physiologic basis of this finding remains un
causing vascular obstruction with respect to the spinal cord. explained, and the study should be repeated with a larger patient
Ischemic insult with petechiae or hemorrhages into the spinal population. If the bony abnormalities or disk lesions producing
cord can produce a sharp interscapular pain followed by lower the myelopathy extend toward the nerve root, a single or multi
limb paresthesia and pain, eventually progressing to lower limb ple radicular injuries may be present. A far enough lateral ex
weakness or paralysis, bowellbladder dysfunction, and other tension may result in injury to the dorsal root ganglion, in which
symptoms consistent most commonly with anterior cord tissue case a reduced SNAP amplitude response with normal periph
damage (posterior columns are often spared). A whole host of eral latencies and conduction velocity can be anticipated. This
toxic substances may result in myelopathy, with those disorders is, however, a very rare finding.
usually progressing slowly (tri-O-cresyl phosphate, iodochlorhy Somatosensory evoked potentials may be of considerable as
droxyquinoline, nitrous oxide, chemotherapeutic drugs) present sistance in defining a lesion affecting the posterior column path
ing with lower limb sensory disturbance and long tract signs, ways in any form of myelopathy. 90S One must recognize,
while those agents resulting in acute paralysis (contrast agents however, that a spinal cord lesion not affecting the posterior
and misplaced spinal anesthetics) presenting with lower limb column pathways can be anticipated to result in a normal
and back pain followed by hypotonic paraparesis or flaccid para study.221 Also, performing both lower and upper limb SEP stud
plegia. Metabolic/nutritional, remote effects of cancer, and ies best assesses a lesion in the cervical region. Lower limb
arachnoiditis can also lead to the above-noted form of slowly SEPs are considerably more sensitive in defining pathology in
progressive myelopathy with lower limb sensory abnormalities, the cervical region, as median and ulnar nerve stimulation may
long tract signs, and varying degrees of paraparesis, while vas result in neural impulses that traverse multiple nerve roots and
cular insults from any cause usually produce a more acute form hence potentially allow some fibers to escape the pathologically
of hypotonic paralysis. affected regions to produce a normal response. 207,280,824.898,899 The
Those disorders resulting in myelitis are quite varied and nu upper limb SEP, when normal but associated with an abnormal
merous (Table 16-3). As noted above, an inflammatory disorder lower limb SEP, helps to confirm that the lesion is likely located
causing a myelitis can evolve over varying time periods. caudal to the brain stem level. The lumbar spine potential is of
Perhaps one of the more common presentations likely to be en great help in defining both a normal peripheral conduction path
countered by clinicians is that of spinal cord involvement ex way and a prolonged central conduction pathway when the con
tending horizontally across the cord to varying degrees as well duction time between the lumbar region and cerebral cortex is
as rostraIly and caudally over several segments, i.e., transverse abnormal.
myelitis. 22 ,71,79,490,676 Patients commonly complain of back pain, The specific findings that may be detected in cervical mye
occasional radicular pain, lower limb sensory disturbances and lopathy with upper limb SEPs can be quite variable. 90s In some
weakness, and the eventual development of bowellbladder dys persons with clinically obvious myelopathy and imaging studies
function. Many but not all patients have symptoms that peak of spinal cord compromise, the SEP may be completely normal.
within 24-48 hours, but several weeks may be required to fully This is the situation referred to above, primarily when median
manifest maximal deficits. The upper limbs can be involved, but nerve studies are utilized in that the neural conducting pathways
this occurrence is less frequent than that described above, as the escape pathologic involvement. On the other hand, some per
lesions are below the cervical region. Hyperreflexia, increased sons may demonstrate a normal Erb's point potential defining
lower limb tone, and extensor plantar responses develop after optimal peripheral conduction; however, the cervical spine po
the initial period of spinal shock. A relatively sharp sensory de tential (NI3/14) may be delayed in latency or more commonly
marcation between normal and abnormal sensation is frequently reduced in amplitude or absent. The subsequent cortical potential
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 621
may be delayed, reduced in amplitude, or only minimally af myelopathies or myelitic diseases. The history and physical ex
fected if the only abnormality is a reduced amplitude cervical amination, however, guide one to the most expedient examina
potential. The majority of patients (75-100%) with clinically tion required to assist in the diagnosis, A patient with no
suspected myelopathy have either a delayed or absent tibial suggestion of radicular disease but only a myelopathy most
nerve SEP, or prolonged central conduction time as measured likely preferentially requires a SEP investigation of both the
from the lumbar spine potential to the cerebral corteX.630,908 The lower and upper limbs, particularly addressing the central con
value in performing SEPs is the documentation of conduction duction times. On the other hand, a thoracic myelitis may need
abnormalities and hence suggestion of myelopathy in patients both a lower limb SEP and thoracic paraspinal/abdominal
with neck pain and radiographic abnormalities, Also, the large muscle needle electromyographic examination to define the
numbers of patients with radiographic abnormalities limit the lesion's location and extent. Preferential motor involvement
value of isolated imaging studies in some persons, and SEPs may be best assessed with magnetically induced motor evoked
help define those persons with myelopathic conduction alter potentials. The electrophysiologic tests and imaging studies are
ations. Of course, a normal SEP can be consistent with true not mutually exclusive but complementary in providing as much
compromise of the spinal cord, particularly if the posterior accurate information as possible toward the formulation of the
columns are not affected by the pathology, Le., preferential most appropriate diagnosis.
pyramidal tract involvement. In patients with anterior spinal
artery syndrome, giant SEP amplitudes can be observed with Spinal Cord Trauma
normallatencies. 831 This finding is similar to that noted above Clinical Aspects. Persons who sustain a spinal cord injury
with large peripheral nerve sensory amplitudes. In both in can be anticipated to demonstrate lower motor neuron weak
stances, the explanation is lacking. ness associated with the damaged spinal cord levels directly
Transcranial magnetic stimulation may be of benefit in defin destroyed by the trauma. Flaccid paralysis and absent reflexes
ing myelopathies, especially those preferentially affecting the are noted in these muscles beyond the period of spinal shock.
motor pathways.2oo,82t.822,827 In persons with clinically proven Significant muscle wasting can also be observed in these
cervical myelopathy, 100% of patients demonstrate abnormali levels. Following spinal shock, the spinal segments below the
ties regarding the magnetically generated cortical motor evoked level of insult display typical upper motor neuron signs of hy
potentials. These studies, however, can be normal in persons perreflexia, spasticity, and increased muscle tone as well as
with pure posterior column disease. In other words, the corti loss of muscle bulk. There is no clinical reason to suspect "den
cally evoked motor potentials and SEPs are complimentary ervation" in the lower limb muscles of a patient with only a
studies. The exact sensitivity and specificity comparing each cervical spinal cord injury. The electrodiagnostic medicine
technique in a large patients population with and without cervi evaluation in patients with spinal cord injury, however, can
cal myelopathy remain to be determined. reveal a number of findings quite similar to those described for
Needle electromyography in patients with involvement of the stroke patients.
central nervous system can be normal or abnormal depending on Electrophysiologic Findings. If the dorsal root ganglion at
the location of the lesion and the muscles examined.616.725,794 If the various injured levels is damaged, the corresponding sen
the ventral gray matter containing the alpha motor neurons is in sory nerve studies demonstrate an absent SNAP or a reduced
jured, the myotomal representation of the affected segments will amplitude if there is only a partial injury.95 Similarly, loss of an
demonstrate positive sharp waves and fibrillation potentials if terior hom cells at the affected spinal segment(s) should pro
the insult is significant enough to damage a number of motor duce a reduction in the CMAP amplitude with little alteration in
neurons, A reduction in the voluntary motor unit recruitment can nerve conduction velocity, Needle electromyographic examina
also be anticipated in the affected muscles. Over time, motor unit tion of muscles innervated by the damaged spinal segments
remodeling through collateral sprouting results in large-ampli should demonstrate significant degrees of positive sharp waves
tude long-duration MUAPs possibly firing at high rates in re and fibrillation potentials. Depending on the degree of insult,
duced numbers. Fasciculation potentials can also be observed in MUAPs mayor may not be present. These findings can all be
patients with cervical myelopathy. An increase in the number of expected given the above-noted insult at the affected segments.
polyphasic MUAPs may also be detected. In persons with cervi Similarly, one may logically conclude that the unaffected seg
cal or lumbosacral cord or cauda equina disease, the above-noted ments above and below (partial injury) the injured regions
membrane instability can be detected with needle electromyog should demonstrate no abnormalities aside from a reduced
raphy, When a thoracic myelopathy is suspected, examination of CMAP amplitude distal to the insult regions (disuse atrophy)
the lower limbs can be anticipated to not demonstrate positive and absent voluntary MUAPs. This apparent logical conclusion,
sharp waves or fibrillation potentials unless the lesion is severe however, is not the case,
enough to produce a complete spinal cord injury, in which case Examination of sensory nerves distal to the injury site, for ex
these potentials may arise from transsynaptic degeneration (see ample, sural nerve in cervical spinal cord injury, has demon
Stroke and Spinal Cord Injury below), In thoracic myelopathies, strated mixed results. Normal conduction velocities and
the thoracic paraspinal muscles and abdominal muscles should latencies are found provided the lower limb temperature is opti
be examined. Detection of abnormalities in thoracic myelopathy mal. 127 The sural SNAP, however, may be normal or reduced,196
can help define the anatomic level and extent of insult to the The reason for the reduced SNAP amplitude is unclear, as the
spinal cord. In some patients, finding bilateral multilevel evi cell bodies in the dorsal root ganglion are unaffected. The find
dence of positive sharp waves and fibrillation potentials, particu ings of reduced SNAP amplitudes below the level of injury re
larly in elderly individuals with suspected cervical spine disease, mains to be substantiated. Motor nerve conduction velocities
suggests not only a polyradiculopathy but also a possible con and distal motor latencies are normal for as long as the CMAP
comitant cervical myelopathy.422 can be recorded. 127,J96,594,816 The most commonly examined nerve
It is clear from the above discussion that a number of electro is the peroneal nerve with recording from the extensor digito
diagnostic techniques are available to assist in the diagnosis of rum brevis muscle. Characteristically, serial studies demonstrate
622 - PART IV CLINICAL APPLICATIONS
a reduction in the CMAP over the course of a year, most likely a There are various etiologies responsible for syringo
result of disuse atrophy and possibly some degree of peroneal myelia/hydromyelia (Table 16-4).889 An attempt can be made at
nerve trauma during transfers. categorizing the various causes by considering those disorders
Needle electromyographic examination of lower limb mus associated with hindbrain deformitiesllesions and non-hind
cles in cervical cord injuries usually reveals the development of brain-related problems. Clinicians treating persons with spinal
positive sharp waves and fibrillation potentials in essentially all cord injuries should be aware of the possibility of post-trau
patients by about 3 weeks and persisting after spinal matic syringomyelia. Approximately 3% or less of persons
shock. 12 ,127,196,594,602,678,779,816 Fasciculation potentials can also be who sustain a traumatic spinal cord insult can develop progres
observed in some patients. This activity peaks by about 4-5 sive weakness and sensory loss above the lesion level either
weeks and then declines over the course of the ensuing 6 acutely following a Valsalva maneuver (e,g., lifting weights,
months. Some patients continue to demonstrate these potentials performing a difficult transfer), or insidiously over the course of
for more than a year following the injury. Persons with com years secondary to the development of syrinx. 49 ,80,840,890 This
plete as well as incomplete lesions may demonstrate the above type of lesion can occur in spinal cord-injured patients as early
noted abnormal spontaneous activity. As spasticity increases, as 2 months or as late as 40 years following the initial spinal
there is noted to be a decrease but not necessarily complete dis cord injury.
appearance of positive sharp waves and fibrillation potentials. The majority of syringomyelic lesions occur between C2 and
Of note, the lumbosacral paraspinal muscles also demonstrate T9-11 spinal levels. 889 These lesions can extend up into the
this form of membrane instability, which appears to be the ex brain stem or descend to varying degrees. If a lumbosacral
ception in persons with stroke. 12 Stimulated single-fiber studies syrinx is present, it is usually associated with a central or para
in the lower limbs of patients with cervical cord injuries demon median cavity at higher levels, although rarely an isolated lum
strate elevations in jitter, suggesting denervation and subsequent bosacral cord syrinx can be detected. 847 The patient's clinical
reinnervation. 138 The exact cause of these findings is unknown presentation is primarily dependent on the location and extent
and may be related to the above speculations of transsynaptic of the cavity with respect to the neuroanatomic pathways af
degeneration detailed for similar potentials in stroke patients. fected (Fig. 16_18).587,619,865,889 A lesion located in the lower cer
vical regions usually results in the patient complaining of a
Syringomyelia/Hydromyelia progressive and relentless deep boring or causalgic type of pain
Clinical Features. Fluid-filled cavities within the spinal cord vaguely associated with the lower cervical or upper thoracic
and/or brain stem regions have been designated differently by spinal segments affecting the upper limbs. Patients may exhibit
various authors, leading to considerable confusion. A dilation of involuntary movements and postures (e.g., segmental spinal
the spinal cord's central canal is referred to as hydromyelia, myoclonus, propriospinal myoclonus, postural hand
whereas a fluid-filled cavity other than the central canal within tremors).587 Careful examination demonstrates a band-like loss
the spinal cord is designated syringomyelia. 27o,722 If there is a in pain and temperature but not vibration and proprioception,
demonstrable communication between the central canal and the i.e., the so-called dissociated sensory loss. The lower limbs
syrinx. this is a communicating syringomyelia, as opposed to a may be completely normal at this point. Progression of the
non-communicating syringomyelia, where there is no demonstra cavity begins to dissect laterally as well as superiorly and infe
ble connection. An exception to this type of discussion is recog riorly between neural tracts, resulting in further disruption of
nized because of well-entrenched terminology, i.e., an extension neurologic function. This extension of the disease process pro
of the central canal into the medulla with dysfunction of brain duces a progression of the loss of pain and temperature sensa
stem structures continues to be referred to as syringobulbia. tion over a large body surface with a possible increase in the
above-noted deep boring type of pain. Deep tendon reflexes in
the upper limbs become depressed or disappear completely,
Table 16-4. Syringomyelia/Hydromyelia Classification and lower limb reflexes become brisk with an increase in
I. Hindbrain-Related II. Nonhindbrain-Related muscle tone and spasticity. Extensor plantar responses can now
A. Hindbrain herniation A. Spinal tumors
be found as well as a spastic paraparesis. A Homer syndrome
may become apparent secondary to disruption of the cervical
Tumor related Intramedullary
sympathetic system. The patient may bum his or her hands, and
Chiari type I Extramedullary
deep cuts may be noted with little in the way of discomfort.
Chiari type II Extradural
Muscle wasting of the hand intrinsic muscles may be detected
Birth trauma Disk disease
where none was present previously. The above findings are
usually bilateral except that there can be significant asymmetry
Nonbirth related trauma B. Dysraphism
to the findings. Sweating may also be prominent in the affected
Bony deformity (basilar invagination) C.Arachnoiditis
body segments. Continued progression of the syrinx into the
Hydrocephalus associated Postinfectious
posterior column and dorsal root zone regions, and superiorly
and inferiorly, results in the same symptoms and signs as
B. Foramen magnum arachnoiditis Post-traumatic
above, but over a wider body surface with the sacral regions re
Birth related D. Bony deformities maining relatively intact until the very late stages of the dis
Trauma related (birth/nonbirth) Tuberculosis ease, i.e., sacral sparing. The bladder may be affected at some
Infection Idiopathic scoliosis point during the later stages of the disease. Also, the bulbar re
gions can be injured with loss of pain and temperature over the
Post-traumatic
face beginning about the ears and progressing toward the nose,
E. Unknown corresponding to the trigeminal nerve's laminated brain stem
From Williams B: Syringomyelia, Neurosurg elin North Am 1990; I :653-685. extensions forming the so-called Dejerine onion skin pattern of
with permission. sensory loss. Further muscle wasting of the affected regions is
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 623
A B
A B
SoIM~"' ___-""
AIIdomItIIIIIgo. -"" ....... brIItIc
Figure 16-1B. Various clinical presentations of syringomyelia based upon the lesion's location and extent. (A) A central located syrinx
results in a deep boring pain vaguely related to the affected spinal segment with associated loss of pain and temperature, but preservation of pos
terior column sensory modalities. No upper motor neuron signs are noted at this time. (8) Expansion of the syrinx into more of the surrounding
spinal cord's substance as well as extending more proximally and distally can occur. The result is involvement of more spinal segments with muscle
wasting in the upper limbs as well as upper motor neuron signs in the lower limbs. (C) Continued expansion of the lesion now begins to affect the
sensory modalities conveyed by the posterior columns. The superior extent of the lesion begins to affect the bulbar nuclei and tracts in addition
to descending to involve the lower limbs. (From Patten J: Neurological Differential Diagnosis. New York. Springer-Verlag, 1982, with permission.)
also noted. Charcot joints located in either the upper or lower The clinical symptoms and signs associated with a syrinx are
limbs can develop in some persons. Scoliosis may appear in in not unique to this type of pathology. Motor neuron disease may
dividuals at a variable time throughout the course of the dis mimic some of the presenting weakness; however, sensory loss is
ease. A lumbar syrinx results in pelvic muscle wasting and not present. Multiple sclerosis is a possible disorder that can clin
lower limb dissociated sensory loss. Bowel and bladder in ically mimic a syrinx in some persons. Cervical spondylosis is
volvement may be earlier than that for a lesion in the cervical also a disease that should be considered in the above clinical pre
region. sentation. The most appropriate diagnostic measure in persons
624 - PART IV CLINICAL APPLICATIONS
with a suspected syrinx is an MRI of the spinal region. 309.460.475.549 the motor cortex and recording CMAPs can be of some help in
Particularly clear images of syringomyelia/hydromyelia can be defining abnormalities affecting the motor conducting pathways,
appreciated on MRI. Surgical intervention directed at draining particularly when combined with peripheral motor stud
the cavity usually halts further progression of the disease, and the ies. 86•523•S82.586.673 Prolongations in minimal F-wave latency deter
pain mayor may not be appreciably improved. mination can be observed in patients with syringomyelia with a
Electrophysiologic Findings. The degree of electrophysio return to normal values following surgical decompressio~ in
logic abnormalities detected by various procedures is directly some persons. 220,491,625 Increased H-reflex responses to condition
dependent on the amount of spinal cord insult. Interestingly, ing stimuli may be noted in patients with spinal myoclonus. 587
there is little in the way of correlation between the morphologic Reportedly, the most frequent electrophysiologic abnormality
appearance of the syrinx and the clinical or electrodiagnostic detected is an alteration of MUAP parameters.197.295,686.850
medicine findings. There is, however, a correlation between the Specifically, recruitment abnormalities are detected in the hand
severity of clinical symptoms and the extent of electrophysio intrinsic muscles, i.e" reduced recruitment with decreased
logic abnormalities detected. The more severely affected a patient MUAP firing at rapid rates. Additional MUAP abnormalities
is clinically, the greater the chance of detecting abnormalities consisting of increased amplitude, duration, and numbers of
on neurophysiologic examination. polyphasic potentials can also be observed. Positive sharp
Recall that the syrinx is located within the spinal cord sub waves and fibrillation potentials can be documented in upper or
stance and may be asymmetrically placed. This lesion is, there lower limb muscles (depending upon the location of the syrinx);
fore, proximal to the dorsal root ganglion cells. As a result, the however, these potentials are usually rather sparse and difficult
sensory nerve conduction studies reveal no abnormalities of to detect. These abnormal spontaneous potentials can also be
SNAP parameters (amplitude, latency, conduction velocity) di detected in the paraspinal region commensurate to the involved
rectly attributable to the syrinx.261.275,49I,686,850 It is important to segments either bilaterally or unilaterally depending upon the
keep in mind, however, that up to 40% of patients with hy extent of the syrinx with respect to the alpha motor neurons bi
dromyelia/syringomyelia have either median nerve lesions at laterally, Of note, a thoracic syringomyelia can preferentially
the wrist (carpal tunnel syndrome) or ulnar nerve lesions at the present with what appears to be at first glance an abdominal
elbow (most likely a result of a Charcot elbow lesion concomi hernia; however, needle electromyography reveals evidence of
tantly injuring the ulnar nerve). In these cases, it is highly likely denervation in the abdominal muscles. 156 The majority of the
that abnormal median and/or ulnar SNAPs can be obtained. It is above routine needle electromyographic findings can be ex
important to assess the possibility of a carpal tunnel syndrome plained by the pathologic nature of syringomyelia because it is
or elbow ulnar neuropathy by performing selective studies to a slowly progressive expanding lesion with progressive loss of
delineate these possibilities. alpha motor neurons. This results in a reduced recruitment of
Because the syrinx is located within the central nervous remodeled motor units comprised of more muscle fibers firing
system, various sensory pathways can be affected. If and when less synchronously, thus creating large-amplitude long-duration
the syrinx cavity begins to disrupt the dorsal horn region or pos polyphasic MUAPs firing in reduced numbers and rapid rates.
terior columns, alterations in SEP parameters can be antici The relatively slow loss of motor unit innervation combined
pated. 29.52 1.662 When performing routine SEPs, both the upper with successful reinnervation produces only a few positive
(median and ulnar) and lower (tibial) limb nerves should be in sharp waves and fibrillation potentials. Fasciculation potentials
vestigated, including the patient's asymptomatic side. The can be found in affected muscles. Myokymia and continuous
asymmetric nature of the syrinx can produce varied findings on motor unit activity have been reported in a few patients with sy
different sides of the body. Expected abnormalities include pro ringobulbia and syringomyelia.587.663 Single-fiber electromyog
longed central conduction times and/or reduced amplitudes or raphy reveals a progressive increase in fiber density values in
absent cervical spine and cortical potentials. The diagnostic the hand intrinsic muscles compared with the forearm muscles
yield is found to be increased if all four limbs are studied with with the least abnormalities noted in the proximal arm muscles
respect to central conduction time abnormalities or cortical po for a cervical syrinx. 729,782 The jitter is mildly elevated, and
tential alterations.394,563 When performing routine upper limb blocking can be present but is noted to be prominent only in pa
SEP studies, a number of patients can have completely normal tients with rapidly progressive disease.
findings. In those persons, the utilization of a cervical spine sur
face electrode referenced to a region on the anterior neck just OTHER CENTRAL DISORDERS THAT MAY AFFECT
superior to the thyroid cartilage can improve the ability to note MOTOR NEURONS
an alteration in the amplitude of the cervical potentiaJ.232.526.662
Because the neural fibers conveying pain and temperature sen Stroke
sation are usually affected before those of posterior column
function, a number of patients may have a normal SEP when Clinical Aspects. Individuals who develop a cerebral stroke
performed in the routine manner during the early course of the or traumatic head injury may demonstrate a number of electro
disease. Special SEP techniques employing CO 2 laser stimula physiologic abnormalities not anticipated given the original
tion preferentially activating the small-caliber neural fibers may concept of upper versus lower motor neurons. There is no
be more sensitive in detecting early syrinx formation.419.654,829 reason to suspect that an insult to the upper motor neuron
Motor nerve conduction studies usually reveal normal distal system should adversely affect the physiologic status of its cor
motor latencies and conduction velocities. With advanced dis responding alpha motor neuron. In fact, however, there appears
ease (significant loss of alpha motor neurons exceeding the ca to be a more intimate physiologic association between them
pacity of collateral sprouting), the evoked CMAP is reduced in than originally suspected. Initial clinical observations on pa
amplitude. In these patients, it is not uncommon for a coincident tients with hemiplegia secondary to vascular occlusion or hem
reduction in nerve conduction velocity approaching 70% of the orrhage demonstrate significant loss of muscle bulk and wasting
lower limit of normal to be observed. Magnetic stimulation of above that anticipated simply due to disuse. The "hemiplegic
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 625
amyotrophy" was proposed to be a combination of disuse, lack transient and can be easily missed. The peak occurrence of these
of some ill-defined trophic substance or control exercised over abnormal potentials is between 3 and 4 weeks following the
the muscle indirectly by the upper motor neurons, and so-called onset of weakness and usually diSSipates by about the sixth
transsynaptic degeneration of the alpha motor neuron resulting month. A few patients may continue to demonstrate these po
from dysfunction of its upper motor neuron. 138a These theories tentials at greater than I year. There appears to be some weak
remain unproven; however, it is interesting to note that muscle correlation between the development of spasticity and return of
biopsy specimens from patients with stroke do indeed demon voluntary control with the disappearance of positive sharp
strate grouped atrophy in addition to widespread atrophy and waves and fibrillation potentials. Rarely, these potentials can be
muscle fiber size variation. 102,146.25 1.755 observed in the paraspinal muscles. In one investigation, fibril
It is important to keep in mind that patients with stroke and lation potentials and positive sharp waves were observed in the
particularly those incuning a traumatic head injury may be sub upper limb only in 50% of patients, both the upper and lower
ject to the development of peripheral nerve injuries.565 Also, limb in 35% of persons, and the lower limb in 15% of individu
those individuals who develop a stroke may have concomitant als. Insertional positive sharp waves appear to be more common
disorders predisposing them toward the disease as well as pe than fibrillation potentials,
ripheral nerve disorders, e,g., diabetes mellitus. In persons with A few investigations in patients with some voluntary con
stroke, malpositioning, traction, or sustained pressure secondary trol reveal a reduced number of MUAPs but with a morphol
to altered sensation can subject the patient to a brachial plexus ogy suggesting an increase in short-duration polyphasic
insult or compression neuropathy (median, ulnar, peroneal neu MUAPs. Over time, the duration and amplitude of the MUAPs
ropathy). Multiple trauma patients can certainly have peripheral increase, suggesting motor unit remodeling through collateral
nerve or brachial/lumbosacral plexus injuries as a result of the sprouting. Further quantitative needle electromyographic stud
traumatic insult. A clinical clue to this type of insult in a patient ies are necessary to better define the MUAP changes in hemi
with decreased communication ability is the observation of plegic limbs.
gross and focal muscle wasting out of proportion to the remain The documentation of positive sharp waves and fibrillation
der of the affected limb. Also, the failure to develop spasticity in potentials in patients with upper motor neuron lesions is impor
particular muscle groups despite its appearance in other mus tant because it challenges the simple idea of these potentials
cles of the same limb may be indicative of a peripheral nerve arising only from denervation or intrinsic muscle disease.
lesion.486 Despite these occurrences, there remains a group of Clearly, stroke patients do not have denervation of their muscle
patients with abnormal electrodiagnostic medicine evaluations as a result of the stroke. What then causes the positive sharp
with no obvious explanation for significant abnormalities noted waves and fibrillation potentials to appear? The best answer at
on needle electromyographic examination. this time is simply that we do not know.
Electrophysiologic Findings. Sensory and motor nerve con
duction studies, including F-waves performed on the affected Head Injury
hemiplegic limb (upperllower Jimb), are normal. m ,775.SOI Prior to A single investigation has evaluated patients with severe
performing nerve conduction studies, it is important to remem and mild head injuries with respect to the documentation of
ber that hemiparetic/hemiplegic limbs may have a reduced fibrillation potentials and positive sharp waves. 775 In those
blood flow and hence be somewhat cooler than the unaffected persons with "mild" head injury (criteria defining mild and
limb. Temperature can have a profound effect on neural conduc severe not provided), there was a complete absence of abnor
tion velocity, and hence the limb's temperature should always mal spontaneous activity in the upper and lower limb muscles
be monitored. Of note, when temperature is considered, a few on needle EMG. However, in those persons with "severe"
investigators have observed that the hemiplegic limb's ulnar head injuries accompanied by upper/lower limb weakness in
nerve conduction velocity and occasionally median nerve ve most but not all patients, prominent fibrillation potentials and
locity may be slower than the contralateral normal limb's con positive sharp waves were noted in the weak limbs as well as
duction velocities. There may be a reduction of 3-4 mls on the unaffected side. The degree and distribution of abnor
between the two sides; however, the reduced conduction veloc mal spontaneous activity were more pronounced in the weak
ity in the affected limb is still within accepted normal compared with unaffected limbs. Sensory nerve studies were
limits.579,608,ffi9 typically normal, as were motor nerve conduction velocities.
Needle electromyographic examinations in the hemipare The evoked CMAP was reduced, suggesting drop-out of
tic/hemiplegic limbs have revealed contradictory results. muscle fibers. The majority of patients examined recovered
Several investigators have found no evidence of positive sharp motor function over time, including CMAP amplitudes, im
waves or fibrillation potentials in the affected limbs irrespective plying that the above findings were not suggestive of a root
of the time of examination following the onset of weak lesion proximal to the dorsal root ganglion. If a root avulsion
ness. 20,21,352 When abnormalities have been noted, they have had been present, the documentation of motor recovery would
been attributed to concomitant brachial or peripheral nerve in be highly unusual.
juries. 147 On the other hand, numerous investigators have docu The presence of fibrillation potentials and positive sharp
mented the development of positive sharp waves and fibrillation waves was always present at 3.5 weeks, which was when the
potentials in the affected limb as early as 7-10 days in up to first examination was performed. It typically peaked by about 7
80% of patients examined.74 ,167.298,404,448 The pattern of abnormal weeks and began to resolve by approximately 10 weeks. If ab
ities in general is noted to be more frequent in the upper com normal spontaneous activity was present on the unaffected side,
pared with lower limbs, with the distal muscles demonstrating it usually abated prior to the more affected side. Of note, the
more numerous abnormal potentials than the proximal documentation of abnormal spontaneous activity on the appar
muscles. 44 .335 Occasionally, the contralateral unaffected limbs ently unaffected side in presumed unilateral lesions suggests
may reveal a few fibrillation potentials and positive sharp waves that subclinical lesions affecting the contralateral hemisphere,
in several of the small hand intrinsic muscles, but these are very or possibly the brain stem, may be present.
626 - PART IV CLINICAL APPLICATIONS
Of course, it is incumbent upon the practitioner to perform a The diagnosis of multiple sclerosis may be assisted by at
careful electrodiagnostic medicine examination to ensure that a tempting to classify patients suspected with the disease into one
concomitant peripheral nerve lesion in a patient sustaining suf of three potential categories: definite, probable, and possible.
ficient trauma to induce a head injury is not present. Muscle For a patient to be classified into the "definite" category, he or
wasting in a peripheral nerve lesion out of proportion to that an she must have (1) a history compatible with relapsing and re
ticipated for disuse atrophy following a head injury is suspi mitting symptoms of at least two bouts separated by about I
cious for a peripheral nerve injury. In this instance, profuse month, or a slow but progressive course for at least 6 months;
abnormal spontaneous activity may be present in all muscles on (2) neurologic signs of lesions affecting the nervous system
the affected side, or possibly more pronounced in those muscles (brain or spinal cord white matter) in two or more sites; (3)
within the injured peripheral nerve territory. However, a careful symptom onset between IO and 50 years; and (4) no other iden
physical examination combined with not only needle EMG, but tifiable neurologic cause for the symptoms and signs. If the his
also motor and sensory studies, may help define the lesion site. tory and physical examination can document only a single
Also, somatosensory evoked potentials may be of assistance in lesion, the demonstration of an abnormality either on MRI of
defining if there is continuity through the brachial plexus, i.e., the nervous system combined with elevated CSF gamma globu
defining if a root lesion is present. Normal sensory responses lin, or an abnormal evoked potential is sufficient to count as a
combined with diffuse abnormal spontaneous activity and low second lesion. A "probable" diagnosis of multiple sclerosis
amplitude CMAPs are consistent with a nerve root avulsion. must include (1) a history of relapsing and remitting illness
However, if somatosensory evoked potentials document a wave without concomitantly documented signs aside from a single
form not only at Erb's point, but also in the cervical region, it is sign usually associated with the disease (see above); (2) a single
unlikely that a nerve root avulsion is present. bout of the disease with documentation of symptoms and signs
of more than a single lesion site with good recovery followed by
Multiple Sclerosis variable symptoms and signs; (3) a lack of an identifiable neu
Clinical Features. Multiple sclerosis is associated with de rologic disease other than multiple sclerosis. For this category,
myelinating lesions separated by time and space. 5•547 Most indi the finding of an abnormality on MRI or evoked potential test
viduals diagnosed with mUltiple sclerosis present between the ing contributes toward the lesion category if one is lacking on
ages of 20 and 40 years. The primary aspect of the symptoms history or physical examination. The "possible" diagnostic cate
and signs of this disease is a dissemination in time and body gory is not accepted by all investigators; however, it may be of
part affected. The symptoms and signs of multiple sclerosis are some use clinically.642 These persons usually have (1) a history
highly variable and dependent on the location of the focal of relapsing and remitting symptoms, but no Objectively ob
region of demyelination. At least 50% of patients present with served signs supportive of the symptoms; (2) insufficient signs
one or more of the following symptoms: muscle weak to define more than a single lesion site; and (3) failure to find a
ness/excess fatigue, altered visual acuity, increased urinary fre better neurologic disease explanation.
quencylhesitancy, gait ataxia, paresthesias (limbs or Lhermitte's The disease has variable prevalence rates depending upon the
sign), band-like sensations about the thorax, dysarthria/scan global location. In equatorial regions, less than I person per
ning speech, or some form of mental disturbance (depres 100,000 population is found with the disease, whereas in the
sion/euphoria). On physical examination, 50% of patients southern United States and Europe, a prevalence between 6 and
demonstrate one or more of the following: limb spasticitylhy 141100,000 population can be noted. On the other hand, in
perreflexia, extensor plantar responses, reduced/absent abdomi northern Europe and Canada, a prevalence of 30-80/100,000
nal reflexes, dysmetria/intentioned tremor, nystagmus, reduced population can be detected. Individuals born in a high-risk
vibration sensation, diminished position sense, decreased pain region but who move to a low-risk region of the world continue
sensation, or variable degrees of unilateral facial weakness. The to carry their original propensity to develop the disease, espe
so-called Charcot's triad of nystagmus, scanning speech, and cially if they move after the age of 15 years. There is also a
intentioned tremor is not usually observed until late in the dis small but present familial risk of developing the disease. A ge
ease process. These symptoms and signs can develop over a rel netic factor is suspected, particularly if a person has the histo
atively short period of time and may resolve over the course of compatibility antigen associated with D or DR locus on
days to weeks, suggesting some form of conduction block as the chromosome 6. Women are affected slightly more than men, ap
initial pathology. Over the course of the ensuing months and proximating 1.5:1.0, until those persons over 60 years of age are
years, variable degrees of symptom attacks manifest and subse concerned, when the ratios equalize.
quently remit frequently, leaving some form of minimal residua, The causative agent responsible for persons developing the
thus producing the classic exacerbations and remission of the characteristic demyelinative plaques is unknown. Two popular
disease. Dysfunction eventually results when sufficient loss of theories include a viral etiology and an autoimmune hypothesis.
axonal transmission ensues. Occasionally, patients with other There is circumstantial evidence for both but conclusive data for
wise typical multiple sclerosis can present with marked muscle neither. The pathophysiology of symptoms and signs in multi
atrophy, particularly of the hand intrinsic muscles (6-7% of pa ple sclerosis is relatively straightforward. Demyelination effec
tients),264.456 or a hypotonic paresis/paralysis of a major portion tively acts to increase the capacitive current loss across the
of limb suggesting a lower motor neuron insult.631.741 Recovery demyelinated internodal region, thus leaving less current avail
of this type of insult occurs in a similar manner to lesions sug able to activate the next in line node of Ranvier. If sufficient
gesting an upper motor neuron location. The exact form of clin myelin is lost, the remaining amount of current can fall below
ical disability is dependent on which aspects of the nervous whatever the critical level is for the ensuing node of Ranvier,
system are preferentially affected. Although most patients expe thus leading to failure of impulse transmission and hence the
rience this disease over the course of decades, a few unfortunate "negative" or "absent" symptoms and signs of the disease.
persons have an acute and aggressive form of the disease that Specifically, impulse failure in afferent tracts leads to reductions
can lead to death in a few weeks to months. in sensation or vision, while impulse failure in motor tracts
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 627
leads to weakness. On the other hand, the loss of myelin effec the more diffuse peripheral nervous system abnormalities noted
tively reduces the insulation between nerves, thus predisposing above. In persons with gross atrophy of muscles, the CMAP
them to form ectopic foci or regions of membrane instability may be reduced but the nerve conduction studies remain
that can then activate neighboring demyelinated nerves, thereby normal, and there is no evidence of a focal entrapment neuropa
giving rise to the so-called positive symptoms. Specifically, thy either clinically or electrophysiologically. Investigations
paresthesias, dysesthesias, and the Lhermitte's sign can arise in have demonstrated a reduced neuromuscular junction transmis
such a manner. Remyelination, if of a sufficient degree, results sion safety factor in that persons with multiple sclerosis took
in re-establishment of the conducting pathways and resolution longer to recover from experimental regional administration of
of the abnormal symptoms or signs. Elevating the patient's core D-tubocurarine compared with a control population. suggesting
temperature can produce a shortening of the action potential and further evidence of a more widespread neurologic involvement
hence reduce the amount of current available. Combining a de than just the central nervous system. 224 F-wave studies may be
myelinative segment (current loss) with an elevation in temper normal or display an increase in chronodispersion or amplitude
ature (less current per impulse) can result in an exacerbation of as compared with the maximal CMAP.225 In persons with pro
the patient's symptoms and signs, most likely accounting for the found muscle wasting. the F-wave can be absent.
worsening of symptoms in the so-called warm bath test. In addi The blink reflex may be of assistance in physiologically doc
tion to the development of central nervous system demyelina umenting a lesion in the pons. 461 Patients with internuclear oph
tion, patients with multiple sclerosis may also demonstrate a thalmoplegia or other brain stem signs have a high degree of
mild to moderate (> 50%) reduction in peripheral nerve myeli abnormalities noted on the blink reflex. Approximately 66% of
nation. If the multiple sclerosis lesion affects the alpha motor patients with definite multiple sclerosis demonstrated an abnor
neurons in the spinal cord, Wallerian degeneration of the corre mal R 1 response, while 56% of patients with probable disease
sponding axons can be anticipated. 504 This suggests that multi had an abnormality.440 The Rl response is more stable and reli
ple sclerosis may not be a disease limited exclusively to the able for detecting lesions than the R2; however, R2 is essential
myelinated tracts of the central nervous system.339.639.723 Aside for helping to localize the lesion. Also, a direct or facial nerve
from documenting the anatomic result of demyelination/re response should be performed to fully complement the informa
myelination by MRI, various electrophysiologic means can be tion gained from the blink reflex.
employed to verify the above-noted failures of transmission.687 Evoked potentials can be of significant benefit in the diagno
Electrophysiologic Findings. The peripheral nerve motor sis of multiple sclerosis. Three types of evoked potentials can be
and sensory nerve conduction studies are completely normal in performed: visual, auditory, and somatosensory.31 ,32.293.438.593.863
patients with pure multiple sclerosis.264.294.815 Of interest, how When comparing all three forms of evoked potentials in patients
ever, are a number of investigations suggesting that there may with definite multiple sclerosis based on clinical criteria, so
be a variable degree of peripheral nervous system involvement matosensory evoked potentials are abnormal in about 90-95%
in some patients with otherwise typical multiple sclerosis. of patients, followed by visual. evoked potential abnormalities in
Studies examining the sensory nerve conduction velocity reveal about 75-90% of patients, with auditory or brain stem evoked
that some persons with this disease have normal maximal con potentials being abnormal in roughly 45-50% of persons. 55 The
duction velocities but reduced minimal conduction velocities. 74O variability in percentages is due to lesion location, different pro
The minimal conduction velocity is represented by the slower tocols, patient selection, and various other factors in study
conducting fibers, which can be resolved by using near-nerve design. Regarding somatosensory evoked potentials, it is impor
needle techniques and evaluating the individual spike compo tant to always perform lower limb (peroneal or tibial nerve)
nents of single nerve or small groups of nerve fibers following studies in addition to median or ulnar nerve stimulations. The
the major spike of the SNAP. Additionally, the refractory period lower compared with upper limb nerve studies significantly in
is prolonged and the supernormal period reduced. 366•74O These crease the diagnostic yield (96% vs. 67%) secondary to increas
findings suggest that there may indeed be subtle peripheral ing the probability of finding a lesion because of the longer
nerve abnormalities possibly owing to mild but similar demyeli anatomic path traversed by the electrical impulse. 32.764 An ab
native changes affecting the peripheral nervous system as those sence or prolongation of a spinal or cortical potential is the
occurring in the central nervous system. usual abnormality, although central conduction times should
A small number of patients with multiple sclerosis may also also be calculated. Lower limb nerve stimulation is particularly
have generalized slowing of sensory and motor nerve conduc important in suspected lesions of the spinal cord because upper
tion velocities and prolongation of distal motor laten limb nerve stimulation may be normal, as would the auditory
cies.671.723.741 These individuals unquestionably have a mild and visual evoked potential studies. Motor evoked potentials
peripheral neuropathy. An etiology other than the multiple scle employing transcranial magnetic stimulation appear to be a
rosis for the peripheral neuropathy cannot be found in the ma valuable addition to the diagnostic armamentarium of electro
jority of these individuals. Occasionally, a patient with multiple physiologic studies, with comparable statistics regarding the de
sclerosis presents with acute or chronic inflammatory demyeli tection of abnormalities as lower limb somatosensory evoked
nating polyradiculoneuropathy, begging the question if this is a potentials. 66•354.52l1.571.6S9 The benefit of this technique is the abil
chance occurrence or some type of physiologic relation ity to strictly evaluate the motor system in patients with prefer
ship.268,471 The question must be asked, therefore, if some per ential motor symptoms and signs. There is considerable
sons have not only a central but also a peripheral nervous discussion regarding the utility of evoked potentials versus
system disorder directly resulting from the causative multiple MRl.129.292,683.S37 The MRi evaluation of patients with all clinical
sclerosis factor similar to that found in experimental allergic en designations of multiple sclerosis continues to yield slightly
cephalomyelitis. To be sure, patients may have focal entrapment higher diagnostic abnormalities than evoked potential studies.
neuropathies in this disease unrelated to the primary pathologic There are exceptions, in that MRI may reveal lesions that are
process, carpal tunnel syndrome and ulnar neuropathy at the clinically silent or completely miss lesions producing clinical
elbow; however, these localized processes cannot account for and electrophysiologic abnormalities. particularly if the entire
628 - PART IV CLINICAL APPLICATIONS
Table 16-S. Involuntary Sustained Motor Unit/Single any type of pathology, implicating an entrapment neuropathy or
Fiber Ac1:iVIt:Y radiculopathy. The reason for these findings is unclear, It is possi
I. Central Nervous System Disorders ble for persons with some form of transverse myelitis, for exam
ple, producing the above-described gross lower motor neuron
A. Stiff-person syndrome
presented with a history of progressive muscle stiffness and pro Table 16·6. StitT·Man Syndrome Versus Isaacs' Syndrome
posed the designation syndrome of continuous muscle fiber Stiff-Man Syndrome Isaacs' Syndrome
activity.3 88 The spontaneous activity continued during genera]
anesthesia and proximal nerve block but was abolished by Postulated site of Central nervous Peripheral motor
curare blockade of neuromusuclar transmission. Therefore, the abnormality system axon
hyperexcitability was believed to arise from the motor nerve. Reaction of motor
Subsequently, the disorder has become known as Isaacs' syn· unit activity to:
drome or acquired neuromyotonia. 337,583 Isaacs' syndrome Neuromuscular block
usually occurs in adults but has been observed in a newborn. 47,78 Peripheral nerve block
The disorder is caused by hyperexcitability of the motor nerves
resulting in continuous activation of muscle fibers. Patients Spinal anesthesia
manifest with diffuse muscle stiffness, widespread muscle General anesthesia
twitching (myokymia), cramps, increased sweating, and occa Sleep
sionally CNS symptoms (e.g., confusion, hallucinations, insom
nia).388,476,583 The myokymia is present continuously even during Diazepam
sleep, which can help distinguish this syndrome from stiff Phenytoin/carbamazepine
person syndrome (see below), in which the motor hyperex J. = decrease; H = no change,
citability improves with sleep, The muscle stiffness worsens
with voluntary activity of the affected body segment. Patients
may experience difficulty relaxing muscles following maximal chronic inflammatory demyelinating polyneuropathies, and au
contraction (Le., pseudomyotonia), Some patients complain of tosomal dominant episodic ataxia. 320,396.466.848.871 Neuromyotonia
muscle weakness associated with a sensation of stiffness. A can also be observed clinically in persons following radiation to
hoarse voice may be noted secondary to continuous contraction the central or peripheral nervous system (brachiallIumbosacral
of the vocal muscles. Reduced breathing capacity can be de plexus, radiation to the brain stem region), pontine demyelina
scribed because of respiratory muscle involvement. Talking, tion (e.g., multiple sclerosis), or following a bite from a rattle
eating, and swallowing may be also be affected. The patients snake.53,195,481,583 Penicillamine may also produce the symptoms
also develop excessive sweating, most likely a result of muscle of neuromyotonia. 661 .
activity. Affected individuals can lose considerable weight Histopathology. Muscle biopsies in individuals with Isaacs'
during the course of the illness, possibly owing to a combina syndrome may be normal or reveal grouped atrophy or fiber
tion of the muscle activity consuming high amounts of energy type grouping suggesting denervation with subsequent reinner
and reduced food intake because of the above-noted eating diffi vation,51,390,391,596 Sural nerve biopsies may be normal or reveal a
culties, The majority of patients do not complain of bowel or mild reduction in myelinated fibers.466 An increase in terminal
bladder incontinence, or impotence. Some patients experience nerve branching can be observed with an elevation in the termi
transient paresthesiae. nal innervation ratio.
Physical examination of the patient generally reveals a some Laboratory Features. In acquired neuromyotonia, radioim
what stiff posture with possible slight trunk flexion, shoulder el munoassays demonstrate antibodies directed against voltage
evation and abduction, and elbow flexion. 396 Contraction of the gated potassium channels (VGKC) in the serum and
trapezius muscles bilaterally may give the patient an appearance CSF.336,337,583 VGKC are present on peripheral motor and sensory
of having a webbed neck. Prominent widespread fasciculations neurons as well as neurons within the CNS. Binding of the anti
and myokymia can be observed and appear as an continuous un bodies to the VGKC leads to inactivation of these channels re
dulating or quivering to the skin overlying the muscles. 5°O sulting in hyperexcitability of the motor nerves (see below).
Fasciculations and myokymia may be particularly prominent in Patients may have other laboratory features associated with con
the facial, pectoral, and calf muscles following attempts at comitant autoimmune diseases. CSF may demonstrate increased
strong muscle contraction. Some individuals may display a de protein, increased immunoglobulins, and oligoclonal bands.
layed relaxation of eye or hand opening following forceful eye Pathogenesis. Isaacs' syndrome is an autoimmune disease
closure or a strong grip (pseudomyotonia). Sensation is normal caused by autoantibodies directed against VGKC located on pe
unless there is an underlying demyelinating or axonal neuropa ripheral nerves. 337,581.744 Of interest, autosomal dominant
thy, in which case there may also be varying degrees of weak episodic ataxia that is associated with generalized myokymia is
ness. Deep tendon reflexes are normal or diminished,861.916 caused by mutations in the VGKC a-subunit gene. II I Ex
Plantar responses are normal. Some individuals may demon perimental passive transfer of serum from patients with ac
strate carpopedal spasms, Chvostek's sign, or Trousseau's sign quired neuromyotonia into mice results in resistance of ex vivo
despite normal calcium levels. 466,596 phrenic nerve-diaphragm preparations to D-tubocurarine. 761
Most patients develop this disease sporadically; however, Other investigations demonstrated that passive transfer experi
several families with apparent autosomal dominant inheritance ments increase quantal content and repetitive firing of dorsal
have been reported. 42 Isaacs' syndrome may occur in associa root ganglia cells in mice injected with sera from Isaacs' syn
tion with other autoimmune disorders (e.g., SLE. systemic scle drome patients compared with normal control sera.744
rosis, celiac disease).583 Paraneoplastic neuromyotonia has been Immunoglobulins from patients with Isaacs' syndrome suppress
reported with lung carcinoma, plasmacytoma, and Hodgkin's voltage-gated potassium currents but do not alter gating kinetics
lymphoma.25.'3o.281,322,583,617.860.862 Acquired neuromyotonia or or significantly affect sodium currents. S73 Blocking these VGKC
Isaacs' syndrome may occur in patients with myasthenia gravis reduces the hyperpolarizing influence of the channel on the
and thymoma. 1,242.350.476.515,S72.583.628.854 Generalized myokymia or axonal membrane, leading to hyperexcitability of the neurons.
neuromyotonia may complicate hereditary motor and sensory Electrophysiologic Findings. The motor and sensory nerve
neuropathies (e.g., Charcot-Marie-Tooth disease), acute or conduction studies as well as F-wave and H-reflex studies are
630 - PART IV CLINICAL APPLICATIONS
F Response
Filt.ers
'W 2 Hz - Hl !<Hz
'F' 50 Hz - 10 !<.Hz
figure , 6-/9. Isaacs' syndrome. Repeti
tive after-discharges are evident on attempt
to record an ulnar F-wave. Note the repet
itive discharges obscure the recording of
any F-waves.
IB 3IiI 10111
"
often reported as normal in patients with the idiopathic or famil The MUAPs may appear in groups of similar appearing but de
ial form of Isaacs' syndrome. 43 ,108,389,396.466,505,S83,596 However, if clining amplitude potentials or a profuse superimposition of
one looks closely or turns up the amplifier's gain, repetitive multiple MUAPs, i.e, doublets, triplets, or multiplets. 376.583
after-discharges are often evident following standard motor con When groups of similar appearing potentials are noted, the in
duction studies. 42 Likewise, it may be difficult to elicit an F terpotential firing frequency may reach 200-300 HZ.388.S83,596
wave or H-reflex because the repetitive after-discharges Usually, a firing rate of recognizable individual MUAPs can be
obscure these potentials (Fig. 16-19). Patients with the heredi observed to fire at 40-50 Hz. A number of small-amplitude
tary form of the disease also have been reported to have repeti short-duration potentials, however, may be quite prominent in
tive firing of the muscle following neural stimulus, thus some patients. These potentials are identical to fibrillation po
generating a repetitive CMAP during routine testing.42 This is a tentials and most likely represent single muscle fiber discharges
similar finding to organophosphate poisoning or a type of con secondary to activation of single muscle fibers by the disease
genital myasthenia with an absence of acetylcholinesterase. Of process. Additionally, MUAPs may be fragmented, as the initi
note, microneurographic recordings reveal spontaneous action ating electrical impulse may originate in the terminal arboriza
potentials not only in motor nerves, but also in sensory nerves, tion of the nerve and result in the activation of small groups of
suggesting that the disease affects both motor and sensory nerve muscle fibers sequentially, as opposed to the more usual syn
fibers despite normal sensation and minimal paresthesias de chronous spread of neural activity from a common peripheral
tected clinically.466 Some patients have acquired neuromyotonia nerve trunk branch point. The net result may be short-duration
complicating acute or chronic inflammatory demyelinating small-amplitude MUAPs larger than the single fiber potentials
polyradiculoneuropathy or the Charcot-Marie-Tooth disease (fibrillation-like potentials), yet smaller than the complete
type II. In these cases, the motor and sensory studies are identi MUAP, thus resembling "myopathic" MUAPs, In the absence
cal to those findings in patients with the more typical clinical of a superimposed peripheral neuropathy, there should be an ab
presentation of the above-noted diseases regarding motor and sence of fibrillation potentials and positive sharp waves.
nerve conduction findings. A voluntary contraction produces an increase in the baseline
The needle electromyographic examination reveals continuous activity of firing MUAPs. In some patients, a brief silent or rela
firing of MUAPs in the majority of skeletal muscles examined in tively silent period may be noted immediately following a bout
cluding the facial and external ocular muscles. 226 The most of voluntary activity. At rest, in addition to the continuous
common abnormal discharges are combinations of fasciculation MUAP firing (neuromyotonic discharges), in those muscles
potentials, doublets, triplets, multiplets, complex repetitive with less exuberant activity, fasciculation potentials or
discharges, and myokymic discharges (Fig. 16_20).108,376,583 myokymic discharges can occasionally be observed. Sleep and
Although the disorder goes by the name of "neuromyotonia," general anesthesia do not significantly alter the MUAP firing
myokymic discharges are much more common, whereas actual pattern. In most patients, peripheral nerve block also does not
neuromyotonic discharges are less frequently observed (Fig. appreciably affect the firing rate. 38B Motor point block or neuro
16-21).396 The above-noted abnormal discharges may arise spon muscular blockade does result in absence of the MUAPs, sub
taneously, or result from needle movement/insertion, after volun stantiating the impression that the abnormality arises in the
tary contraction, neural ischemia, or neural percussion. terminal nerve arborization. 583 A number of patients have
Of note, the MUAPs are of normal morphology in most in demonstrated a reduction in the muscle fiber activity following
stances with no evidence of increased amplitude or duration. peripheral nerve block, suggesting that there may be a combination
Chapter 16 DISORDERSAffECTING MOTOR NEURONS - 631
of irritable foci along various aspects of the peripheral nervous by muscular rigidity and episodic spasms involving truncal and
system including the central nervous system,387.395.505,709 limb muscles. 10,14,151,178,304,491,531,532,559,599,635.771.172,888 Patients with
Treatment. Various modes of immunomodulation appear to SPS develop increasing "stiffness" of the thoracic and lum
be beneficial in some patients, including plasmapheresis. IVIG. bosacral paraspinal, the abdominal, and proximal lower limb
and corticosteroid treatment.43.S83.161,844 Symptomatic treatment muscles in the second to sixth decade of life. In addition, there is
with antiepileptic medications (e.g., phenytoin, carbamazepine, superimposed "attacks" of intense muscle spasms or contractions.
and gabapentin) may also be useful as well, perhaps by decreas These spasms are usually triggered by loud noises creating a star
ing neuronal excitability by blocking sodium channels. 108,390 tle response, emotional upset, or physical activity and are charac
terized by intense contraction of the hip and knee extensors. ankle
Stiff·Person/Stiff·Limb Syndrome dorsiflexors. and occasionally abdominaUparaspinal muscles.
Clinical Features. Moersh and Woltman were the first to de Importantly, the muscle stiffness and spasms are not present
scribe 14 patients with the disorder that they termed "stiff-man during sleep. The stiffness and muscle spasms usually lead to gait
syndrome."559 Because the disorder is more common in women impairment with occasional falls. Patients may complain of dysp
than in men, stiff-person syndrome has to be the preferable nea secondary to chest restriction as a result of stiffness in the
term.175 It is the co-contraction of both agonist and antagonist thoracic muscles.115 In addition, paroxysmal autonomic dysfunc
muscles that produces the muscle stiffness and rigidity. Some tion characterized by transient hyperpyrexia, diaphoresis, tachyp
have clinically subdivided stiff-person syndrome into three subdi nea, tachycardia, hypertension, pupillary dilation, and occasional
visions: (1) progressive encephalomyelitis with rigidity. (2) sudden death may accompany the attacks of muscle spasm. 17S.5S8,791
typical stiff·person syndrome (SPS), and (3) stiff-limb syn Stiff-limb syndrome is characterized by asymmetric rigidity and
drome. 47 Progressive encephalomyelitis with rigidity is a rapidly spasms in the distal limbs or face. 105,707.774 However, Dalakas and
progressive disorder associated with generalized stiffness, en colleagues noted that most of their patients with typical general
cephalopathy, myoclonus, and respiratory distress that is usually ized SPS started out asymmetrically and called into question the
fatal within 6-16 weeks. 47,374,426,815'!Ypical SPS is characterized so-called stiff-limb syndrome as a distinct entity.175
Needle EMG
There is an increased incidence of insulin-dependent diabetes appear to inhibit GABA synthesis. 2Q1 ,m.m Loss of function of
mellitus (IDDM) and various autoimmune disorders (Hashi GABA-mediated inhibition on central motor neurons may lead
moto's thyroiditis, pernicious anemia, hypoparathyroidism, to hyperactivity. Electrophysiologic studies suggest that there is
adrenal failure, myasthenia gravis, systemic lupus erythemato a loss of intracortical inhibition by GABAergic neurons of the
sus, rheumatoid arthritis, ovarian disease, vitiligo).24.'75,531,532 cerebral cortex as opposed to inhibition at the spinal cord
Approximately 10% of patients also have generalized seizures level.265.483,713
or myoclonus. 14,24.175,479.514.531.532 There are reports of SPS associ Electrophysiologic Findings. Sensory and motor conduc
ated with Hodgkin's lymphoma,311 small-cell carcimona of the tion studies are usually normal. 24 ,39.162,178.211.372,392,sIO,535.539,558,595,664
lung,54 and cancers of the colon and breast. 267 ,311 SPS also can A few patients with normal sensory but abnormal nerve conduc
occur in patients with myasthenia gravis and thymoma. 3II .584 tion velocities have been reported; however, it is unclear if these
There have been reports of a congenital SPS; some inherited in persons had a concomitant mild peripheral neuropathy sec
an autosomal dominant fashion.~43,489.714 However, these cases ondary to diabetes mellitus. Repetitive nerve stimulation is also
may represent familial hyperexplexia caused by mutations in normal in these patients. Because the loss of GABAergic input
the glycine receptor. 186 into motor neurons is predicted to result in tonic firing of the
The physical examination is remarkable for exaggerated motor neurons and their hyperexcitability to sensory stimuli,
lumbar lordososis and paraspinal muscle hypertrophy sec Floeter and colleagues measured the strength of reciprocal inhi
ondary to continuous paras pinal muscle contraction. Intense bition between pairs of antagonist muscles. 265 They found that
muscle contraction of the axial muscles (paraspinal, abdominal, spinal circuits mediating reciprocal inhibition were normal; thus
intercostal muscles) and proximallower limb muscles are ob they speculated that reciprocal inhibition was located in
served. As noted above, asymmetric involvement at the onset is supraspinal circuits. Paired-pulsed transcranial magnetic stimu
not uncommon, and occasionally the distal limbs may be pre lation of the motor cortex demonstrated greater facilitation: pa
dominantly affected early in the disease course. Further, stiff tients with SPS had motor evoked potentials 2-2.5 times greater
ness may involve the facial muscles. Manual muscle testing is than those of controls, suggesting that hyperexcitability of the
usually normal, as is sensation to all modalities throughout. motor cortex was caused by the loss of intracortical inhibition
However, a concomitant mild peripheral neuropathy may be by GABAergic neurons of the cerebral cortex. 483 ,7J3 Visual, brain
found in patients with IDDM. Deep tendon reflexes may be stem auditory, and somatosensory evoked potentials are
normal or slightly increased. Plantar responses are typically normaI.539.541
flexor, although a few patients may have demonstrated an ex The characteristic abnormality with respect to SPS is de
tensor response. 175.558 tected with needle electromyography. The affected axial and
Laboratory Features. Autoantibodies directed against the limb muscles demonstrate MUAPs with normal morphologies
64-kD glutamic acid decarboxylase (GAD) are evident in (amplitude, duration, phases) firing continuously. The patient
60% of primary autoimmune cases of SMS.24.175,306.311.483.531.532 cannot produce electrical silence in these muscles despite all at
Of note, GAD is highly concentrated in pancreatic islet cells, tempts at relaxation. The firing rate of the activated motor units
and anti-islet cell antibodies that are often found in patients is not abnormally high, with firing rates at or below 20-30 Hz.
with IDDM are directed against GAD. This likely explains the Voluntary contraction results in an increase in the numbers and
30% incidence of IDDM in patients with SPS. Occasional pa firing rates of MUAPs. There is a distinct lack of abnormal
tients have antibodies directed against an 80-kD antigen compo MUAPs or spontaneous potentials in the way of fibrillation po
nent of GAD as opposed to the 64-kD antigen.179 Further, tentials, positive sharp waves, or complex repetitive discharges.
antibodies directed against a 128-kD presynaptic protein, am Following administration of diazepam, the patient demonstrates
phiphysin, are present in some patients with presumed parane a reduction in the firing of MUAPs. In addition, general and
oplastic SPS.267.682 The CSF is often abnormal in patients with spinal anesthesia as well as peripheral nerve blockade also re
SPS, demonstrating increased IgG synthesis, oligoclonal bands, sults in a reduction or cessation of the motor unit activity.304
and anti-GAD antibodies. Other autoantibodies and laboratory Sleep also causes the motor unit activity to abate. 39,211,685
abnormalities are associated with concomitant autoimmune dis Treatment. Patients with suspected SPS typically respond
orders (e.g., Hashimoto's thyroiditis, pernicious anemia, hy well to diazepam and related compounds, owing to the modula
poparathyroidism, adrenal failure, myasthenia gravis, systemic tor effects these medications have on the GABAergic transmis
lupus erythematosus, rheumatoid arthritis).175.636 Serum CK sion. Diazepam may be sufficient in some patients at a dosage
levels may be slightly elevated, owing to the almost constant of 5-10 mg 3-4 times per day, although some patients have
state of contraction of various muscle groupS.175 been reported requiring up to 300 mg per day.I53·115,492,532.540
Histopathology. Autopsy studies in patients with en Clonazepam,175 dantrium,175 methocarbamol,858 valproate,777 vi
cephalomyelitis with rigidity syndrome have revealed lympho gabatrin,I75,731 gabapentin,175 botulinum toxin injection, 182 and
cytic infiltrate involving the cerebral cortex, brain stem, and oraI550,873 as well as intrathecal baclofen542,733,752,789 may also effi
spinal cord .314,426,815 There are very little histologic data regard cacious in some patients. Several patients have been reported to
ing SPS and stiff-limb syndrome. Autopsies of two patients respond to immunosuppression,333.378 IVIG,24,46.423,437,714 or
with SPS who died unexpectedly from paroxysmal autonomic plasma exchange 96,333,855; however, benefit was not found in all
hyperactivity revealed perivascular gliosis in the spinal cord and patients.
brain stem in one patient and lymphocytic perivascular inflam
mation in the basal ganglia, brain stem, and spinal cord in the Additional Disorders with Continuous Single
other patient. 558 Vacuolar degeneration of anterior hom cells has Muscle Fiber or Motor Unit Activity
also been reportedJo8 Sural nerve and muscle biopsies have A number of additional clinical disorders besides Isaacs' syn
been unremarkable. 392,535 drome and stiff-person syndrome can have variable periods of
Pathogenesis. GAD is the rate-limiting step in the produc sustained motor unit or single muscle fiber activity as detected
tion of gamma-aminobutyric acid (GABA), and GAD antibodies by needle electromyography. Myokymia, single or grouped
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 633
motor units firing for a few seconds at 2-60 Hz, and motor unit neurologic problem. If a person with profound neurologic
discharges with or without cramps active for variable time peri deficit appears to be indifferent to the problem (Ia belle indif
ods can be observed in a many clinical conditions arising from ference), a hysterical conversion reaction should be suspected
quite different causes (Table 16_5).279.283.371,412.699.773.842.867 The provided there is a lack of a cerebral lesion potentially affect
commonality is an irritable peripheral nerve focus resulting in ing the patient's affect. Symptoms may be noted to be exacer
the generation of motor unit discharges. Neuromyotonic dis bated when the examination is directed to a particular body
charges, on the other hand, are related to Isaacs' syndrome (neu segment or when family members are present. A complete res
romyotonia). Unfortunately, a number of investigators do not olution of symptoms may be documented over time irrespec
strictly define terms and use the designation neuromyotonia tive of how profound the initial neurologic deficits.
whenever involuntary activation of motor units is encountered Hysterical patterns of blindness, deafness, and sensory/motor
instead of the more appropriate term of continuous motor unit loss are the most frequently encountered neurologic problems.
activity. Also, the term myokymia is poorly understood and im When psychogenic blindness is suspected, the patient may still
properly used. All reports describing various electrophysiologic fixate on moving objects and demonstrate optokinetic nystag
phenomena should be carefully analyzed with respect to ac mus. Pupillary light reactions and funduscopic examination are
cepted nomenclature (see Glossary). normal. It is possible, however, for various acute disorders to
result in true vision loss prior to the development of optic atro
Hysteria/Malingering phy. If hysterical deafness is suspected, a startle response can
Clinical Features. For our purposes, we may define hysteria sometimes be elicited. In the case of sensory loss, it is common
or conversion reaction as a functional (psychogenic) as opposed for patients to complain of a complete loss of sensation over a
to organic disorder that results in an alteration of a patient's sen particular body segment to all modalities. The common de
sory or motor function without a definable anatomic/physio crease in vibration or position sense alone is rarely if ever ob
logic lesion.143.188.473.629.82o The hysterical symptoms and signs served. Of particular importance is the nonanatomic loss of
are believed to represent an unconscious coping mechanism sensation that does not conform to peripheral nerves, root or
providing the patient with primary gains (relief from anxiety) segmental distributions, or central tracts. An abrupt as opposed
and secondary gains (avoidance of responsibilities causing anx to a gradual loss of sensation at a joint line or skin fold is highly
iety and possible control over others). True organic disease can suspicious of a nonorganic lesion. Motor abnormalities can
be confused with a conversion reaction as demonstrated by var occur in hysteria and present as paralysis/paresis or hyperkine
ious studies documenting 13-30% of patients presumed to have sias (tremors/spasms). Some persons complain of an inability to
psychogenic disease in fact having organic disease to account stand or ambulate and when asked to do so, reveal extremely ex
for their symptoms.285.657.763.791 An individual who is malinger aggerated gyrations of the limbs and trunk. but do not fall or
ing, however, is consciously appearing to be afflicted with a dis gently collapse onto a chair or nearby supporting object. Upon
ease to acquire some type of gain, most commonly monetary, or sitting or lying down, there is noted to be little in the way of an
to avoid some form of adverse reaction such as legal action. In abnormality commensurate with the previously observed limita
either case, the person does not have an organic basis for their tions. When testing the affected limb. the examiner may note
dysfunction. It is not the practitioner's role to cast judgment on that the patient appears to be putting forth great effort in at
these persons, but to utilize the history. physical examination, tempting the task to the point of turning red in the face, grunt
and relevant diagnostic techniques to define the possible pres ing, and grimacing. A partially paralyzed limb may be observed
ence or absence of an organic lesion, and to thereby assist in the to move very slowly, in reality indicating that there is sufficient
formulation of an appropriate treatment plan. From an electro strength present to control the limb against gravity as opposed
diagnostic medicine standpoint, we shall consider hysteria and to falling quickly, as would be expected in true paralysis. It is
malingering equivalent important to watch patients remove and put on clothing, as the
It is to be noted that patients may initially present with claimed weakness may be absent for the brief periods of time
symptoms and signs quite convincing of organic disease with required to manipulate clothing or maintain balance. When per
the potential for invoking a complete and expensive diagnostic forming the history and physical examination, it is important to
work-up. A careful history and physical examination, however, not attempt to confront the patient at that time regarding sus
should reveal a number of inconsistencies in the patient's ex pected psychogenic lesions.
amination that are incompatible with the manner in which the Electropbysiologic Findings. Sensory nerve conduction
body reacts to disease. An initial suspicion of psychogenic studies can be anticipated to be completely normal in persons
based disease may be raised when the symptoms do not con with solely a functional loss of sensation.597.885 It is important to
form with any type of organic illness, primarily because these keep in mind, however, that diseases proximal to the dorsal root
symptoms are based on the patient's concept of how a particu ganglion can also present with normal SNAPs. For example, a
lar disease should present. Of particular importance is the com cervical root avulsion injury or radiculopathy disrupts the affer
plete absence of pathologic signs as determined by physical ent portion of the sensory system proximal to the dorsal root
examination when compared with the maximal patient symp ganglion. As a result, the peripheral extension of the intact cell
toms. For example, one may find complete paralysis of the body remains viable and continues to produce a normal SNAP
lower limbs with normal muscle tone and reflexes in addition in response to peripheral nerve stimulation. The central process
to the absence of pathologic reflexes or increased tone. of the cell body proximal to the lesion site degenerates and re
Although not always accurate, patients may have relatively sults in a clinical diminution of sensation. A normal sensory
normal bowel and bladder function in the face of what should study, therefore, implies the following: (I) lesion of insufficient
be either flaccid or spastic paralysis. 35 A previous history of magnitude to be detected, (2) neural insult proximal to the
psychiatric illness, treatment, or stresses is important to at dorsal root ganglion, (3) no organic lesion affecting the sensory
tempt to define. Most patients are between the ages of 10 and pathway, or (4) technical problems such as volume-conducted
30 years of age when diagnosed with some type of psychogenic responses or the wrong nerve is examined.
634 - PART IV CLINICAL APPLICATIONS
It is possible to also examine the central extensions of the af positive sharp waves and fibrillation potentials within 2-3 weeks
ferent cell bodies located in the dorsal root ganglion regions by of the injury. Also, a reduction in the MUAP recruitment is also
employing visual, brain stem auditory, and somatosensory noted, especially in profound insults. A patient who presents
evoked responses. 373 Visual evoked potentials are normal in per with complete or significant paralysis of the limbs should always
sons with hysterical blindness. When using visual evoked re be examined with needle electromyography if there is any ques
sponses, it is a good idea to employ the checkerboard pattern tion as to the nature, degree, and location of insult. By 3-4
reversal method of generating a stimulus as opposed to the weeks, patients with peripheral (brachial/lumbosacral plexus,
flash-evoked method to ensure response stability and minimize nerve trunk, cauda equina) or central (spinal cord injury and pos
false-negative studies. A few patients with retrochiasmallesions sibly stroke) nervous system insults resulting in paralysis should
(cortical blindness) have been reported to have normal pattern demonstrate positive sharp waves and fibrillation potentials. A
reversal studies, and thus it is suggested that half-field or quad reduction in the number of motor units firing under voluntary
ran tic studies be performed. Brain stem auditory evoked re control is also noted. Persons with profound paralysis secondary
sponses are also normal in persons with psychogenic to a presumed peripheral nerve lesion should have their motor
deafness. 77o Similar to visual studies, a few patients with bitem unit recruitment analyzed. Specifically, minimal contractions are
poral cortical infarcts and complaints of deafness may have all that is required, and the time interval of the first recruited
normal brain stem auditory evoked studies. motor unit is analyzed with respect to when the second motor
The use of somatosensory evoked responses is a bit involved unit is recruited, i.e., recruitment interval/frequency. Normal per
with respect to defining true organic from psychogenically sons and those with hysterical/malingering paralysis recruit their
based sensory IOSS.208.421.484 Persons with psychogenic lesions second MUAP between 8 and 12 Hz (125-83 ms), and this
can always be expected to have normal somatosensory evoked cannot be altered by volition. A person with profound nerve
responses to peripheral nerve stimulation when the motor damage can only recruit MUAPs with a significant increase in
threshold is reached provided true organic pathology is also not the recruitment frequency approaching 20 Hz or more. It should,
present. Unfortunately, there are limitations to this test from the therefore, be possible to distinguish true from psychogenic
perspective of anatomic pathways. It is certainly possible for in weakness. The production of a complete interference pattern is
dividuals with dysfunction of the anterior portion of the spinal not necessary, and thus the technique of determining recruitment
cord (e.g., anterior spinal artery infarction) to have normal so frequencies in suspected cases of hysteria or malingering is
matosensory evoked potentials despite an absence of pain and much more fruitful than attempting to have the patient maxi
temperature sensation. This is because the somatosensory path mally contract a muscle to observe a so-called full interference
ways mediating the response traverse primarily the posterior pattern. Of course, at least some degree of patient cooperation is
columns, which would be spared in the above example. Patients required in order for the examination to be successful. Some pa
can also render a study technically inadequate secondary to a tients may only produce very brief bursts of MUAP activity, in
failure of muscle relaxation. Therefore, when abnormalities are which case little information can be gained.
found, true pathology can be suspected; however, in the instance
of a normal study, there mayor may not be organic disease pre
sent. Stimulation of the motor pathways using cortical magnetic ELECTRODIAGNOSTIC MEDICINE
stimulation can be of assistance in attempting to answer the CONSULTATION PITFALLS
question of an organic lesion in motor paralysis. 399,637 In the
above example of an anterior spinal cord insult, the motor A number of electrodiagnostic medicine consultation pitfalls
evoked response to the muscles below the lesion should be ab must be considered when examining persons with suspected
normal. Continued investigations into the utility and safety of central nervous system dysfunction. Of the disorders discussed
magnetic cortical stimulation is warranted. in this chapter, the motor neuron disorders are most likely to be
Stimulation of peripheral nerves and the subsequent recording evaluated by practitioners. The combination of amyotrophy
of a CMAP are of help in defining the presence of true pathology with normal sensory findings on physical examination is rather
affecting the peripheral nervous system. In the case of hysteric unique, especially if upper motor neuron signs are noted, and
paralysis, the motor nerve conduction studies can be anticipated should not pose considerable diagnostic difficulty. However,
to be normal. It is possible, however, for lesions proximal to the persons with or without motor neuron disorders can have com
anterior hom cell to result in normal CMAP parameters. Only if plicating factors that increase the difficulty of diagnosis, espe
a lower motor neuron peripheral nerve injury is suspected can cially from an electrodiagnostic medicine standpoint. Also,
the motor portion of the electrodiagnostic examination be of various technical aspects of the electrodiagnostic instrument or
considerable help. If a peripheral nerve injury is claimed to have physiologic aspects of the peripheral nervous system may arise
completely severed a nerve, then after about 10 days, there and thus result in some diagnostic dilemmas. Some of the more
should be an absence of the CMAP from the affected muscles. In common issues are discussed that may pose diagnostic chal
partial nerve injuries, a reduction in CMAP amplitude is antici lenges from the perspective of false-positive and false-negative
pated. If a normal CMAP is obtained despite total paralysis, examinations.
either secondary gain should be suspected, or a profound con
duction block is present. The issue of a conduction block can be FALSE-POSITIVES
addressed if there is an absence or significant reduction in the
CMAP with stimulation proximal to the presumed lesion site Instrumentation
compared with an excitation site distal to the lesion. Recording Electrodes. One of the most important parame
Needle electromyography can be of significant benefit in de ters to be considered with respect to nerve conduction studies
termining if an organic lesion is present affecting the peripheral and possibly motor neuron disease is the CMAP amplitude. If
neuromusculoskeletal system.398 Any form of significant peripheral the active and reference recording electrodes are located too
nerve injury producing axonal loss results in the development of close together on active muscle tissue, the ensuing response can
Chapter 16 DISORDERSAFFECTING MOTOR NEURONS - 635
pace with de nervation thus minimizing the occurrence of posi History. This individual is a 54-year-old male with a com
tive sharp waves and fibrillation potentials. In this instance, the plaint of frequently catching his feet on rough pavement or on
only abnormality is large-amplitude long-duration MUAPs, plush carpet during ambulation. Over the past 4-6 months he
which can, therefore, be misinterpreted with too-high a low has noted increasing difficulty ambulating with tripping on
frequency filter. Decreasing the high-frequency filter has the uneven surfaces particularly after walking long distances. This
primary effect of reducing the MUAP amplitude, thus reducing could be avoided until just recently if a conscious effort ~as
the possibility of observing high-amplitude potentials, which made to raise his feet more than normal when walking. The pa
may be easier to detect than long-duration potentials simply be tient states he has decreased endurance for many physical activ
cause most practitioners are familiar with looking for amplitude ities previously performed easily. As an aside, the patient notes
but not duration changes. he has had increasing twitching of the muscles in his legs with
some degree of muscle twitching in his arms and hands. Several
Physiology times a day the patient describes muscles cramping of a mild to
Perhaps the most important physiologic aspect to keep in mind moderate degree in his leg muscles. He denies any numbness or
with respect to persons with suspected motor neuron disease is other types of annoying sensations in his hands or feet. There
that of temperature. In addition to weakness and wasting, an im are no problems noted with bowel or bladder function. The pa
portant consequence to loss of muscle tissue is a reduction in limb tients states that there may be some difficulty swallowing, but
temperature. The decreased temperature can have profound effects he is not sure of this complaint. He denies anyone else in his
on the nerve conduction portion of the examination. Failing to family having had problems similar to his. The patient denies
maintain the limb at optimal temperatures can result in prolonga taking any medication except for a multivitamin and is not ex
tions of distal motor latencies and SNAP latencies as well as re posed to hazardous chemicals or solvents either at work or with
ductions in conduction velocity for both motor and sensory nerves respect to recreational activities. Additionally, there is no ab
and increases in SNAP amplitudes. Thus, it is possible for a person dominal discomfort and he does not smoke or consume alcohoL
with motor neuron disease to have considerable reductions in A recent routine chest x-ray was reported as normaL
nerve conduction velocity of both motor and sensory nerves sug Physical Examination. The patient is an alert and very co
gesting a clinical impression of a peripheral neuropathy. In this operative individual who is noted on gross inspection to be
case, the diagnosis of motor neuron disease can be misinterpreted rather thin with a suggestion of muscle wasting in the distal as
as a peripheral neuropathy. Observing a slow sensory nerve con pects of the lower limbs and feet bilaterally as well as the hand
duction velocity combined with a large amplitude potential is not intrinsic muscles. Ambulation without shoes reveals a steppage
the typical physiologic pattern. This finding should serve as a "red gait on a level floor. Upon gross inspection of the patient's
flag" that temperature may be a confounding factor. shoes, there is noted to be excessive wear on the sole portion of
the toe box. Fasciculations are noted in the upper and lower
Multiple Disorders limbs bilaterally. Deep tendon reflexes are brisk throughout
There is no doubt that one of the most challenging diagnoses with extensor plantar responses. A Hoffman reflex is present bi
to make is that of a motor neuron disease in a patient with some laterally. Five to 6 beats of clonus are present at the ankles bilat
type of axonal peripheral neuropathy secondary to a disorder like erally with some degree of increased tone in the lower limbs.
diabetes or excess alcohol consumption. In these disorders, the Manual muscle testing reveals the hip and shoulder girdles to
sensory and motor conduction studies are abnormal with re have a grade 4/5 strength while the distal limb muscles in the
duced SNAPs and CMAPs, respectively, combined with reduced upper and lower limbs are 3+/5 with the exception of the ankle
MUAPs of long duration and increased amplitude as well as pos dorsiflexors and evertors which are 3/5 on the right and 3-/5 on
itive sharp waves and fibrillation potentials. Because the anterior the left. Sensation testing to all modalities in the upper and
hom cell and peripheral nerve are the final common pathway, it lower limbs are well preserved. Finger-to-nose and heel-to-shin
may be impossible to state with assurance that a motor neuron testing are normal. The only deficit noted on cranial nerve ex
disorder is either present or absent when a significant peripheral amination are a few fasciculations in the tongue; however, there
neuropathy is present, thus predisposing the study to that of a is no gross wasting of the tongue at this time. The patient has
false-negative. If a mild peripheral nerve disorder is present, the some difficulty manipulating small objects with the hands.
combination of electrophysiologic and clinical findings may Nerve Conduction Studies. Nerve conduction studies are
help differentiate several disorders. However, in persons with performed in the right upper and lower limbs as well as on the
significant peripheral nerve loss, the degree of upper motor right side of the face. The mid-palm temperature is heated to
neuron signs, if present, owing to some form of central nervous 32.5°C on the right and 31.5°C posterior to the right lateral
system abnormality may be masked, thus limiting the clinical malleolus.
examination's ability to unquestionably tease out multiple super
Nerve DSL SAmp DML M-Amp NCV F-wave
imposed disorders. At times, it is necessary to acknowledge the
(ms) ()lV) (ms) (mV) (m/s) ms
limitations of the electrophysiologic testing with respect to dif
RFacial 3.2 3.4
ferentiating multiple disorders affecting the motor unit.
RMedian 3.5 35.5 3.9 2.8 52.0 28.0
RMedian 1.9
(7.0 cm)
ILLUSTRATIVE CASE R Ulnar 3.3 29.5 3.4 2.2 54.0 27.5
R Peroneal 3.1 22.5 4.5 Absent
DIFFICULTY AMBULATING ASSOCIATED R Tibial 4.1 1.1 38.0 55
WITH FOOTDROP R Sural 3.8 15.0
Reason for Referral. Patient complaining of "catching" feet Note: There is an absence of evidence to suggest conduction
during ambulation. block in any of the motor nerves studies when comparing the
Chapter 16 DISORDERS AFFECTING MOTOR NEURONS - 637
CMAPs duration, and proximal versus distal amplitudes. An H preserved velocities, and widespread muscle membrane insta
reflex could be consistently obtained from the abductor digiti bility combined with large amplitude long duration motor unit
minimi and abductor pollicis brevis. action potentials is consistent with a chronic neurogenic process
DSL: distal sensory latency; S Amp: sensory amplitude; affecting preferentially the motor system. Primarily motor
DML: distal motor latency; M Amp: motor amplitude; NCV: system disease combined with the clinical findings of upper
nerve conduction velocity; ms: milliseconds; !JV: microvolts; motor neuron signs are consistent with a motor neuron disease
m V: millivolts; m/s: meter/second. Motor and sensory ampli such as amyotrophic lateral sclerosis.
tudes are measured baseline-to-peak. Sensory latencies are mea
sured to peak while motor latencies are measured to initial Recommendation
negative onset. 1. The patient would benefit from a referral to a multimodal
NeedJe Electromyography. A needle electromyographic in ity ALS clinic where he can be evaluated by neurology, physia
vestigation was performed on the right upper and bilateral lower try, physical therapy, occupational therapy, speech therapy,
limbs as well as in the right cranial nerve musculature using a respiratory therapy, psychiatry, and social services.
disposable monopolar needle. 2. The patient may be offered treatment with riluzole and/or
Muscle Rest Activity may opt to enroll in experimental treatment protocols.
Recruitment
Tongue Silent Normal Comment
Supraspinatus 1+ Fibs/PSWs Reduced
Deltoid 1+ FibsIPSWs The above history and physical examination construct a clini
Reduced
Biceps brachii 1+ FibsIPSWs cal presentation consistent with a combined upper and lower
Reduced
Triceps 1+ FibsIPSWs motor neuron disorder. Hyperreflexia, extensor plantar re
Reduced
sponses, and increased limb tone all suggest some type of re
Pronator teres 1+ FibsIPSWs Reduced
Extensor digitorum Rare FibsIPSWs lease phenomena affecting the descending motor pathways.
Normal
Communis Documenting fasciculations and muscle amyotrophy (wasting
and weakness), combined with normal sensory findings, implies
First dorsal interosseous 1+ FibsIPSWs Reduced
a disease preferentially affecting the lower motor neuron.
Paraspinal C4-T9 1+ Fibs/PSW Normal
Incorporating all of these findings with the patient's age, lack of
Tensor fascia lata 1+ FibsIPSWs Reduced
bowel or bladder complaints, and absence of musculoskeletal
Gluteus maximus Silent Normal
symptoms suggesting degenerative spine disease best fits the di
Vastus medialis 1+ FibsIPSWs Reduced
agnosis of amyotrophic lateral sclerosis. These clinical impres
Tibialis anterior 3+ Fibs/PSWs Reduced
sions are substantiated by the electrophysiologic findings
Gastrocnemius 2+ Fibs/PSWs Reduced
during the electrodiagnostic medicine examination.
L I-S 1 paraspinals 1+ Fibs/PSWs Reduced
In the face of obvious muscle wasting, it is important to ade
Comment. Fasciculation potentials are noted in all muscle quately assess this patient's sensory nerve conduction studies.
examined. The majority of muscle groups revealed active dener The upper and lower limb sensory conduction studies are well
vation in the form of fibrillation potentials and positive sharp within acceptable limits for a patient of this age. SNAP ampli
waves. Motor unit action potentials demonstrated amplitudes in tude and latency were normal, suggesting that if a lesion is pre
excess of 5-10 m V in all muscles with a preponderance of ab sent affecting the peripheral nervous system, it is either very
normally prolonged MUAP durations. MUAPs were polyphasic mild or proximal to the dorsal root ganglion. Muscle weakness
in morphology and demonstrated decreased recruitment. The and atrophy, however, suggest that the lesion is not insignifi
left and right lower limb muscles were rather symmetric with cant, and therefore should also affect the sensory system unless
respect to electrophysiologic abnormalities. a primarily motor peripheral neuropathy is present. This latter
possibility is unlikely, given the upper motor neuron signs noted
Summary of Findings on clinical examination and lack of conduction block or other
1. The evoked CMAPs in the upper and lower limbs are re features of demyelination. Additional remote possibilities of a
duced in amplitude. primary axonal type of motor neuropathy (axonal because of the
2. Motor nerve conduction studies are normal in the upper normal motor conduction velocities) preferentially sparing, to
limbs and absent or borderline abnormal in the lower limbs. some degree, sensory fibers include acute axonal Guillain-Barre
There was no evidence of conduction block or other features of syndrome, porphyria, neuronal form of Charcot-Marie-Tooth,
demyelination. lead intoxication, dapsone/vincristine, remote effects of cancer,
3. Sensory nerve conduction studies are normaL and hexacarbon exposure. None of these possibilities are
4. F waves are normal for this individual's height (190.5 cm). consistent with the patient's history or symptoms. Needle elec
5. Needle electromyographic examination demonstrates pos tromyographic examination demonstrates widespread mem
itive sharp waves and fibrillation potentials in essentially all brane instability in the form of positive sharp waves and
muscles tested with a few exceptions noted above. There is a fibrillation potentials. The documentation of these potentials in
concomitant reduced MUAP recruitment accompanied by an in multiple thoracic paraspinal regions suggests that degenerative
crease above normal in MUAPs with elevated amplitudes and spine disease is not a likely cause for the symptoms because this
durations. region of the body is rarely involved in this process with respect
to needle electromyographic abnormalities. Also, fasciculation
Electrodiagnostic Medicine Impression potentials are detected in multiple muscles, suggesting instabil
This patient demonstrates a history and physical examination ity at some level of the motor unit. The MUAP abnormalities
suspicious for a combined upper and lower motor neuron lesion. are consistent with motor unit remodeling, suggesting a process
The electrophysiologic data of normal sensory potentials, re of denervation and reinnervation. Unfortunately, the clinical and
duced amplitude motor conduction studies with relatively well electrodiagnostic findings are most consistent with the motor
618 - PART IV CLINICAL APflLlCATIONS
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26. Ames BN: Endogenous oxidative DNA damage, aging and cancer. Free Radical
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There are a number of well-described as well as poorly de 28. Andermann F, Cosgrove JBR, LLoyd-Smith DL: Facial myok.ymia in multiple
fined disorders that can affect various portions of the central sclerosis. Brain 1961 ;84:31-44.
nervous system. The specific electrodiagnostic medicine find 29. Andersen NE, Frith RW, Synek. VM: Somatosensory evoked potentials in sy
ringomyelia. J Neurol Neurosurg Psychiatry 1986;49:1407-1410.
ings can be of considerable assistance in many instances with 30. Andersen PM, Nilsson P, Kernen M-L: Phenotypic heterogeneity in motor
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870. Welch KMA. Goldberg DM: Serum creatine phosphokinase in motor neuron 897. Worrall BB. Rowland LP. Chin LP. Mastrianni JA: Amyotrophy in prion dis
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Chapter 17
CHAPTER aUTUNE
A number of cranial nerves can be affected by focal lesions, The cranial nerves react to neural insult in essentially the
or become involved in more systemic diseases. This chapter same way as the peripheral nerves (see Chapter 4). Some form
concentrates on focal cranial neuropathies involving the fifth, of neural compromise can result in various degrees of damage
seventh, tenth, eleventh, and twelfth cranial nerves. These to the axon, myelin sheath, or both. This nerve damage is then
nerves are preferentially discussed as they can be evaluated by reflected in characteristic electrophysiologic findings during the
most practitioners during the electrodiagnostic medicine con electrodiagnostic medicine consultation.
sultation. It is certainly possible to assess the second and
eighth cranial nerves through electrophysiologic means; how
ever, visual and brainstem evoked potential details are not ad ELECTRODIAGNOSTIC MEDICINE
dressed in this text. The possibility also exists of evaluating EVALUATION
the extraocular muscles innervated by the third, fourth, and
sixth cranial nerves with needle electromyography.68-70.87.441 HISTORY
This study is rarely performed, requires special expertise, and
is of little practical value except in focal lesions of the above A directed history is performed based on one's clinical suspi
noted cranial nerves. As a result, evaluation of the cranial cion for a compromise of a particular cranial nerve. It is also
nerves responsible for extraocular muscle control is not pur important for the practitioner to determine if the cranial nerve is
sued further. injured superior to, at, or distal to the nerve's nucleus, i.e., an
654 - PART IV CLINICAL APPLICATIONS
upper or lower motor neuron injury. Both the patient's presenta loss when used relatively early on in the disease process, prior
tion and subsequent symptoms are important in deciding to the occurrence of significant collateral sprouting in incom
whether the neural injury is supranuclear or infranuclear. plete injuries. The second major use of amplitude is with respect
to formulating a prognosis, especially for the facial nerve in
PHYSICAL EXAMINATION Bell's palsy.
The physical examination of suspected cranial neuropathies Late Responses (H-Reflex and F-Wave)
is not limited to the motor and sensory distribution of the af Both the H-reflex and F-wave are of minimal value in evalu
fected nerve, but should include careful examination of all the ating cranial neuropathies. Although it is possible to obtain F
cranial nerves. This is because of the relative proximity of the waves from the seventh and eleventh cranial nerves, these
cranial nerve nuclei in the central nervous system as well as wavefonns have not been extensively used for diagnostic or
their relationships upon exiting the central nervous system. prognostic purposes. H-reflexes are not readily obtainable from
Additionally, both the upper and lower limbs must be evaluated, the cranial musculature.
particularly with respect to signs and findings suggestive of a
more widespread insult to either the central or peripheral ner Somatosensory Evoked Potentials (SEPs)
vous system. Of particular interest is the general tone and As noted above, SNAP measurements are not obtained on the
strength of the upper and lower limbs. Also, the deep tendon re cranial nerves; however, it is possible to study the afferent cuta
flexes as well as the presence of abnormal reflexes should be neous sensory component of the primary cranial nerve supply
examined. ing the face, i.e., the trigeminal nerve through the use of SEPs.
Despite the fact that this chapter is concerned primarily with One may stimulate the angle of the mouth (upper lips, lower
cranial neuropathies that are readily assessed by routine electro lips, or both) in order to obtain cortical responses representative
physiologic means, it is still the practitioner's responsibility to of the second or third sensory division of the fifth cranial nerve;
be aware of cranial nerve findings suggestive of neurologic however, this practice has been questioned (see below).
emergencies. Although this aspect of the neurologic examina
tion is beyond the scope of this text, the reader is referred to Blink Reflex
standard texts on this subject and should be prepared to deal One can stimulate the supraorbital nerve at the supraorbital
with these situations expeditiously.2,38.597,614.738 notch and record two ensuing responses from the orbicularis
oculi generating the blink renex. The excited afferent compo
NERVE CONDUCTION STUDIES nent traverses the first division of the trigeminal nerve and is
speculated to split into two separate pathways in the central ner
Unfortunately, there are only a limited number of cranial nerves vous system. The first pathway ascends to the principle sensory
amenable to routine electrophysiologic testing. Additionally, the nucleus and synapses in this structure. A descending pathway
number of tests available to evaluate each cranial nerve is lim carries the induced impulses to the motor nucleus of the facial
ited. This is primarily because of the relative inaccessibility of nerve to result in an ipsilateral contraction of the orbicularis
most cranial nerves. The net result is that the end organ associ oculi muscle generating the first response of the blink reflex re
ated with each nerve is usually the region examined and assess ferred to as Rl (response 1). This pathway is believed to contain
ments must be based on indirect evidence of potential few (2-3) synapses (oligosynaptic).376,711.722 The second pro
pathology. It is usually not possible to activate the affected posed pathway carries descending impulses into the medulla
neural structures both proximal and distal to the presumed oblongata, which then splits into two separate ascending paths
lesion site as is commonly done with peripheral nerves, nor can fonning an ipsilateral and contralateral tract. These two neural
one usually examine both motor and sensory components of impulses again synapse in their respective motor nucleus of the
each cranial nerve. In short, as much infonnation is gathered as facial nerve to exit the skull and generate a bilateral contraction
possible, but this often leaves much to be desired in the evalua of the orbicularis oculi muscle, thus producing an ipsilateral and
tion of a cranial nerve lesion. contralateral (to the side of stimulation) second responses, Le.,
R2 (response 2). These pathways are polysynaptic, as they are
Sensory Nerve Conduction Studies thought to contain significantly more synapses than the previ
Unlike the peripheral nervous system, one cannot employ ously described Rl pathway. This R2 response is considerably
routine neural stimulation techniques in order to obtain cranial delayed compared to Rl because of the longer pathway in
nerve SNAPs. The majority of cranial nerves simply do not have volved. Although the Rl wavefonn possesses a slight variability
cutaneous sensory components, and those that do are not secondary to the multiple synapses, each generating a different
amenable to yielding easily obtainable responses. delay with each successive stimuli, the R2 wavefonn is consid
erably more variable because of the interposition of more
Motor Nerve Conduction Studies synapses. The blink reflex consists of an afferent or orthodromic
It is possible to perfonn motor conduction studies on two cra fifth nerve, and efferent or orthodromic seventh nerve compo
nial nerves, the facial and spinal accessory nerves. Nerve con nent generating an ipsilateral Rl and a bilateral R2, Therefore,
duction velocities are not usually obtained for these nerves as this technique can be used in lesions affecting both the fifth and
the distances are relatively short and the course of the nerves do seventh cranial nerves.
not form a straight line. As a result, side-to-side and reference
database latency comparisons are preferred. The side-to-side Needle Electromyography
compound muscle action potential amplitude (CMAP) ampli The needle electromyographic examination is an extremely
tude is perhaps the most valuable parameter commonly used. important aspect of the electrodiagnostic medicine evaluation
This is particularly important from two perspectives. First, the for suspected cranial neuropathies. This technique can be used
CMAP allows a rough approximation of the degree of axonal in the diagnostic assessment of all cranial nerves discussed in
Chapter 17 FOCAL CRANIAL NEUROp~rHIES - 655
AW'iculo
telflporalller'llll
Middle -mil
geal artery
Maxillary artery
Nerve to mylohyoid
grand
Figure 17-1. The trigeminal ganglion. The trigeminal ganglion is depicted with its three major divisions: ophthalmic, maxillary, and mandibu
lar.The additional branching of these divisions is also depicted. (From Williams PL,Warwick R, Dyson M, et aI: Gray's Anatomy, 37th ed. Edinburgh,
Churchill Livingstone, 1989, with permission.)
this chapter. The two basic aspects of this examination are to complete voluntary MUAP silence. In this case, the patient
document the presence of membrane instability and evaluate should be asked to contract the muscle vigorously and then to
voluntary motor units. Finding positive sharp waves and fibril relax several times. This usually results in a better appreciation
lation potentials documents the muscle's deprivation of its nerve of voluntary versus spontaneous activity. Exploring several dif
supply, while detecting voluntary motor units defines an incom ferent sites may also help distinguish between these two electri
plete lesion and neural continuity. These findings are especially cal potentials. It is also a good idea to use a faster sweep speed
important in the evaluation of cranial neuropathies because of (e.g., 5 ms/div) when attempting to evaluate facial muscle
the lack of extensive nerve conduction techniques. MUAPs, thus improving the instrument's resolution.
A word of caution is necessary when examining the cranial
musculature, especially muscles innervated by the facial and re
current/superior laryngeal nerves. The motor unit action poten TRIGEMINAL NERVE
tials (MUAPs) have particularly short durations and in some
patients relatively small amplitudes. This can result in two ANATOMY AND NEURAL BRANCHING
major areas of confusion. The first is potentially confusing fib
rillation potentials with voluntary MUAPs. It is absolutely nec The largest cranial nerve, trigeminal nerve, is rather com
essary for the patient to completely relax during the needle plex and only those anatomic portions and relationships
examination, thereby ensuring electrical silence from inner amenable to electrophysiologic testing are discussed. The
vated muscle fibers. From time to time, however, the practi trigeminal nerve is comprised of two major components: sen
tioner may not be sure of the patient's ability to produce sory and motor.45.IIS.Z27.5S9.146 There are two types of sensory
656 - PART IV CLINICAL APPLICATIONS
Ophthalmic Nerve
The smallest and most superior of the three divisions of the
trigeminal nerve is composed solely of sensory fibers and is
called the ophthalmic nerve (Fig. 17-1). This nerve provides
sensation to the eyeball, lacrimal gland, conjunctiva, a por
Figure f 7·2. Cutaneous fields of innervation to the head and tion of the nasal mucosa and cutaneous region of the nose,
neck. The three divisions of the trigeminal nerve. ophthalmic (I). max eyelids, and the anterosuperior region of the scalp (Fig. 17-2).
illary (II). and mandibular (III) are depicted with indivtdual cutaneous There are three subcomponent nerves of the ophthalmic nerve
branches also shown within each major territory of innervation. B. that provide the above noted regions with sensation and all
buccal. IT, infratrochlear; L, lacrimal; Ne, external nasal branch of the three fuse just proximal to the superior orbital fissure. These
nasociliary; ST. supratrochlear; ZF. zygomaticofacial; ZT, zygomati three branches are the lacrimal, frontal, and nasociliary
cotemporal. (From Haymaker W: Bing's Local Diagnosis in Neurologic branches. The lacrimal nerve pierces the lacrimal gland to
Diseases. Saint Louis, CV Mosby, 1969, with permission.) supply it, and then terminates in the cutaneous regions of the
upper eyelid. The largest branch of the ophthalmic nerve is
fibers contained in the trigeminal nerve. General somatic exte the frontal nerve. It enters the orbit through the superior or
roceptive afferent fibers convey sensations from the cutaneous bital fissure and then divides into a large supraorbital and a
regions of the face and frontal portion of the scalp as well as smaller supratrochlear nerve. The supraorbital nerve be
mucous membranes of the face and head. These fibers have their comes superficial by traversing the supraorbital notch or fora
cell bodies located in the trigeminal (semiluuar or Gasserian) men to ascend the anterior aspect of the scalp and split into
ganglion. General somatic proprioceptive afferent nerves multiple cutaneous branches, providing cutaneous innerva
travel in the mandibular nerve and originate from cell bodies tion to the forehead and scalp as far posterior as the lambdoid
located in the rostral brainstem within the mesencephalic nu suture. Additional regions supplied by this nerve are the
cleus. Special visceral efferent motor nerve fibers originating in upper eyelid, conjunctiva, and mucosa of the frontal sinus.
the rostral pons traverse the mandibular nerve to innervate the The importance of this nerve with respect to electrodiagnostic
muscles of mastication and several additional muscles. medicine evaluations is that it is stimulated at the supraorbital
The most conspicuous structure of the trigeminal nerve is the notch when attempting to perform a blink reflex. The supra
trigeminal ganglion located at the apex of the petrous temporal trochlear nerve also supplies the conjunctiva and upper eyelid
bone within a dural covered recess (Fig 17-1). From this struc and terminates in cutaneous branches to the inferior portion
ture arise the three major divisions of the trigeminal nerve: oph of the forehead near the midline. The nasociliary nerve passes
thalmic. maxillary, and mandibular. The general somatic through the anterior ethmoidal foramen to become the ante
nerve fibers' cell bodies constitute a large portion of the gan rior ethmoidal uerve, provides neural branches to the nasal
glion and generate centrally and peripherally directed axons. cavity's mucosal membranes, and terminates as the external
The central extensions from the sensory root of the trigeminal nasal branch. Additional small branches are given off the
nerve enter the pons and project dorsomedially toward the prin nasociliary nerve to supply the skin of the eyelids, conjunc
cipal sensory nucleus. Prior to reaching this structure, about tiva, lacrimal sa~, mucous membranes of the sinuses, and a
half of the fibers split into ascending and descending branches, portion of the nasal septum.
while the remaining fibers also ascend and descend but do not
branch. The descending fibers consist of thinly myelinated or Maxillary Nerve
unmyelinated (primarily conveying pain and temperature sensa The intermediate division of the trigeminal nerve, maxillary
tion) nerves that converge to form the spinal tract of the nerve, is also totally sensory in nature. This portion of the
trigeminal nerve. This structure may extend as far caudally as trigeminal nerve traverses the cavernous sinus to exit this region
the upper cervical spinal segments. Neural fibers extend from through the foramen rotundum and crosses the superior aspect
this tract to synapse with neurons in the spinal trigeminal nu of the pterygopalatine fossa to enter the orbit through the infe
cleus. A number of the ascending neural fibers are substantially rior orbital fissure (Fig. 17-1). Once in the orbit, the nerve is re
myelinated (tactile sensation) and synapse in the principal sen ferred to as the iufraorbital nerve. The infraorbital nerve
sory nucleus, which is positioned medial to the middle cerebellar terminates by dividing into multiple branches under cover of the
Chapter 17 FOCAL CRANIAL NEUROPATHIES - 657
levator labii superioris muscle to innervate the skin and mucous FOCAL TRIGEMINAL NERVE NEUROPATHIES
membranes of the cheek and upper lip as well as the nasal ala
and lower eyelid (Fig. 17-2). Multiple branches arise along the The true incidence and prevalence of focal trigeminal neu
course of the maxillary/infraorbital nerve in the cranial cavity ropathies is unknown primarily because sufficiently large multi
(meningeal branch), pterygopalatine fossa (ganglionic, zygo center studies have not been performed. Most of the relatively
matic, posterior superior alveolar [dental] branches), infraor large series of trigeminal neuropathies primarily reflect the par
bital canal (middle superior alveolar [dental], and anterior ticular referral patterns of the reporting physicians. Similar
superior alveolar [dental] branches), and on the face (palpebral, comments apply to the etiology of trigeminal nerve lesions. For
nasal, superior labial branches). Only the cutaneous branches the purposes of this discussion we divide trigeminal neurop
can be easily stimulated for evaluation purposes during the elec athies into sites of potential nerve insult: (1) peripheral trigemi
trodiagnostic medicine examination. nal nerve, (2) trigeminal ganglion, (3) trigeminal root zone, and
(4) central trigeminal pathways.636
Mandibular Nerve
Of the trigeminal nerve's three divisions, the mandibular Peripheral Trigeminal Nerve
nerve is the largest (Fig. 17-1). The mandibular nerve has two As previously stated, the trigeminal nerve provides cutaneous
components, a large sensory and smaller motor root. The sen and mucous membrane sensation to large portions of the head
sory root departs the lateral margin of the trigeminal ganglion to region as well as innervates the muscles of mastication and several
traverse the foramen ovale. The motor root passes beneath the other muscles concerned with mandibular motion. Lesions affect
trigeminal ganglion and fuses with the sensory root just distal to ing individual peripheral trigeminal nerve branches can be ex
the foramen ovale between the tensor veli palatini (medial pected to result in localized deficits pertaining to the function of the
pterygoid) and lateral pterygoid muscles. Motor and sensory injured nerve. One of the more common causes of trigeminal nerve
branches diverge from the mandibular nerve along its entire insult is craniofacial trauma and dental diseaseJextrac
course. A meningeal branch arises to re-enter the cranium and tion.18.95.23Z,279.452 Traumatic insult to the supraorbital and supra
supply the middle cranial fossa's dura mater. A smaller nerve trochlear nerves can result in numbness about the forehead and
then arises, nerve to tbe medial pterygoid, to innervate the more superior portions of the skull. Dental extraction for impacted
tensor tympani and tensor veli palatine muscles. wisdom teeth can lead to significant pain secondary to involvement
The mandibular nerve then splits into an anterior and poste of alveolar branches of the maxillary or mandibular divisions of the
rior trunk. Several motor and sensory nerves arise from the an trigeminal nerve. It is also possible for an infection of the maxillary
terior trunk. A buccal nerve descends toward the mandibular sinus to result in significant discomfort as mediated by the infraor
ramus and unites with the buccal branches of the facial nerve. bital nerve. Tumors about the peripheral nerves, either primary or
This nerve innervates the lateral pterygoid while piercing this metastatic, can arise from the face, mouth, tongue, paranasal sinus,
muscle on its way to join the facial nerve. The skin over the an and base of the skull to directly or indirectly compromise various
terior aspect of the buccinator muscle is supplied as well as the peripheral nerve branches. 147,175.302.497 Cavemous sinus thrombosis
mucous membrane lining the inner surface of this muscle. or carotid artery aneurysm can preferentially affect the ophthalmic
Anterior and posterior deep temporal nerves arise from the division of the trigeminal nerve with pain and altered sensation in
mandibular nerve to innervate the temporalis and masseter mus the distribution of this branch as well as be associated with a third
cles. A separate branch, nerve to tbe lateral pterygoid, sup nerve palsy. The trigeminal nerve is particularly vulnerable to
plies the lateral pterygoid muscle. toxins such as stilbamidine and trichloroethylene or their break
The posterior trunk of the mandibular nerve is considerably down products.96.IOO.124.189.481,661 Although multiple cranial nerves
larger than the anterior trunk and is primarily sensory, but may can be affected, the trigeminal nerve appears to be particularly vul
contain a few motor fibers from the trigeminal nerve's motor nerable. In years past, during general anesthesia, trichloroethylene
root. Three major branches arise from the posterior trunk: au chemically reacted with the soda-lime contained in the closed-cir
riculotemporal, lingual, and inferior alveolar (dental) nerves cuit anesthesia instrument to yield dichloracetylene, which then at
(Fig. 17-1). The auriculotemporal nerve supplies a portion of tacked the motor and sensory components of the trigeminal nerve.
the ear, including the skin of the tragus and possibly a small In various disease states the trigeminal nuclei may be preferentially
region of the helix, external acoustic meatus, tympanic mem affected with residual loss of their peripheral extensions.
brane, temporomandibular joint, secretomotor fibers to the Additionally, systemic diseases potentially can affect multiple cra
parotid, and the skin of the temporal region. Sensory fibers from nial nerves with a propensity for damage to the trigeminal nerve.
the presulcal mucosa of the tongue, floor of the mouth, and gin Mixed connective tissue disorders,59,416.634 systemic lupus erythe
giva of the mandible all join to form the lingual nerve. The matosus,29.37.419,429 dermatomyositis,29,692 scleroderma, 187.692
chorda tympani nerve and a branch from the inferior alveolar Sjogren's syndrome,346.361.686 sarcoidosis,145.331 amyloidosis,82,475
nerve also join the lingual nerve. The inferior alveolar nerve Guillain-Barre syndrome,547 chronic inflammatory demyelinating
enters the mandibular canal through the mandibular foramen, polyradiculoneuropathy,255 chronic renal failure,672 Charcot-Marie
thereby running beneath the teeth to supply each of them. This Tooth disease,369 diabetes mellitus,369 congenital trigeminal neu
nerve then terminates by traversing the mental foramen and ropathy (e.g., Goldenhar-Gorlin syndrome), 14 and sickle cell
forming incisive and mental branches. The inferior alveolar disorders28 all can result in trigeminal neuropathies.
nerve gives off the mylobyoid nerve prior to entering the When patients present with numbness about the chin region
mandibular foramen, which innervates the mylohyoid muscle (numb cbin syndrome), a lesion affecting the mental nerve or
and anterior belly of the digastric muscle. The terminal mental mandibular division should be suspected.94.212.45O In elderly patients
nerve emerges from the mental foramen beneath the depressor this may be a result of mandibular atrophy with impingement of
anguli oris muscle and divides into terminal branches to supply the mental nerve. The possibilities of trauma and drug toxicity
the skin on the chin region as well as the skin and mucosa of the also need to be considered; however, most often a tumor is the
lower lip (Fig. ] 7-2). cause. 94 Some of the above disorders may affect more than just
658 - PART IV CLINICAL APPLICATIONS
the peripheral nervous system such as the trigeminal ganglion trigeminal nerve distribution can rarely occur from intrinsic
and nuclei within the central nervous system, but all usually in tumors of the pons or medulla. 86 A rare cause of altered trigemi
volve the peripheral portion of the trigeminal nerve. nal function may arise secondary to syringObulbia or upper cer
vical cord syringomyelia,554 Multiple sclerosis may generate
Trigeminal Ganglion plaques in strategic locations along the central pathways, medi
Two of the most important disorders affecting the trigeminal ating the information conveyed by the peripheral branche.s of
ganglion are infections and tumors. Infection of the trigeminal the trigeminal nerve and generating a number of trigeminal
ganglion by herpes zoster is believed to be the most common site nerve symptoms.107.279.522,602
of sensory ganglion involvement with the ophthalmic division
involved in a ratio of 4:1 compared to the maxillary and Patient Presentation
mandibular division. 250,301,636.675 ,701 Involvement of all three divi The exact patient presentation depends upon the location of
sions of the trigeminal nerve rarely occurs, Occasionally the the offending agent with respect to the various components of
third, fourth, and sixth nerves may be concomitantly involved the trigeminal nerve noted above. 284 ,548,591 Most patients com
with the trigeminal nerve. The cells located in the ganglion as plain of a combination of sensory loss involving some or all of
well as their central and peripheral extensions demonstrate pro the three divisions of the nerve, pain of a mild to excruciating
found Wallerian degeneration. Patients with acute herpetic neu nature, and weakness of jaw opening/closing.
ralgia of the head and neck may respond to gabapentin.'94 Herpes When a slowly progressive loss of sensation in the trigeminal
simplex virus is also associated with trigeminal nerve dysfunc nerve distribution is combined with diminished control of ex
tion. 4 ,161.233,387 Following an infection with this virus, there can be traocular motion and loss of vision, a tumor affecting the cav
permanent loss of sensation in the various branches of the nerve, ernous sinus region should be suspected. Should the patient
particularly the maxillary and mandibular divisions. Atypical complain of hearing loss, tinnitus, ataxia, possible hemifacial
facial neuralgia and primary sensory neuropathy may be a result weakness or spasm, combined with deficits in the inferiorly lo
of trigeminal ganglion involvement in some cases. cated cranial nerves, a posterior fossa tumor may be present.
Tumors affecting the trigeminal ganglion are relatively un Physical examination of patients with suspected trigeminal
common and are believed to represent approximately 0.2% of all nerve involvement may reveal a diminution in sensation to touch
intracranial neoplasms. 149 A common tumor type affecting the and pain perception in anyone of the three major sensory divi
trigeminal ganglion is a neurinoma or schwannoma, and repre sions as correlated with the patient's complaints, When the oph
sents less than 2% of intracranial neurinomas with about 98% of thalmic division is affected, a reduction or loss of the ipsilateral
these tumors representing acoustic neuromas. 137,149,285,33O,383,426,505,524 corneal reflex may be appreciated with sparing of the contralat
These tumors grow rather slowly and can get quite large, They eral reflex response. Stimulation of the involved upper and lower
are most commonly located in the middle cranial fossa with a nasal mucosa can fail to lead to a sneeze if the ophthalmic and
few positioned in the posterior cranial fossa and an occasional maxillary divisions are damaged, respectively. In addition to sen
tumor extending into both regions of the cranium conforming to sory changes, motor alterations may also be noted. Asking the
a dumbbell shape. It is not uncommon for the sixth cranial nerve patient to bite firmly and relax several times without separating
and occasionally the seventh through twelfth cranial nerves to the teeth allows one to palpate the masseter and temporalis mus
also be affected by these tumors. Rarely, the tumor may extend cles to gain an appreciation of both bulk and firmness. Unilateral
into the orbit and impair vision with an associated exophthal pterygoid muscle weakness produces lateral movement of the
mos. Primary malignant tumors such as schwannoma, neurofi mandible only toward the side of the lesion, and when the patient
brosarcoma, and melanotic nerve sheath tumors can also affect relaxes the mandible, it deviates toward the affected side because
the ganglion.330.423,561,601 Meningiomas may also compromise the of the imbalance in muscle tone. Difficulty in opening the mouth
trigeminal ganglion. 60I .727 is also noted, particularly in bilateral neural injury as the digas
tric, mylohyoid, and pterygoid muscles are weak. The palatopha
Trigeminal Root Zone ryngeal arch may be noted to be lower on the affected compared
The root entry zone (sensory fibers) and root exit zone (motor to nonaffected side. An absent jaw reflex suggests fibers travers
fibers) of the trigeminal root fibers can be injured by a number of ing the mandibular division are compromised. 238 Loss of pain
space-occupying lesions, vascular malformations, systemic dis and temperature sensation with sparing of touch sensibility may
orders, and possible infectious agents. Tumors such as acoustic indicate a lesion in the lower medulla or upper cervical spinal
neuromas, meningiomas, and cholesteatomas can compress the cord affecting the spinal tract or nucleus of the trigeminal nerve.
delicate root fibers. I,5o.234,525,727 Additionally, various malignant Magnetic resonance imaging (MRI) should be performed in all
primary and metastatic tumors can also present with trigeminal patients suspected of having a mass lesion affecting any portion
symptoms. Perhaps the most common form of root entry/exit of the trigeminal nerve.430,578,764,765,766,767
zone lesion is compromise of the neural fibers by vascular mal Two remarkable disorders, idiopathic trigeminal neuropa
formations or arterial loops, particularly of the superior cerebel thy and trigeminal neuralgia, may result from any of the
lar artery or branches of the basi1ar arteryP·80·211,262,263,265,266,485,780 above-noted causes of trigeminal nerve dysfunction. These dis
Syphilis can rarely affect the root portion of the trigeminal orders are a result of a trigeminal nerve lesion and primarily
nerve. 554,636,748 manifest as facial numbness in the former and excruciating pain
in the latter syndrome. A thorough medical evaluation is neces
Central Trigeminal Pathway sary when either of these two findings are present to identify an
Various ascending and descending central trigeminal path etiologic and hopefully treatable cause for the symptoms.
ways can be damaged by a rather diverse group of lesions.
Infarction of the posterior inferior cerebellar or vertebral artery Idiopathic Trigeminal Neuropathy
can result in dysfunction of the descending trigeminal tract in This disorder may be defined as a disorder of sensation localized
the lateral medulla oblongata,279 Primarily sensory loss in the to one or more divisions of the trigeminal nerve with occasional
Chapter 17 FOCAL CRANIAL NEUROPATHIES - 659
weakness of the muscles innervated by the motor portion of the sensations or muscle strength. It is to be noted, however, that
nerve. 232 Persons with numbness of the face may also complain conflicting reports regarding tactile stimulation thresholds with
of a dull ache, coldness, tingling, or a pulling sensation affect von Frey testing have been described, with some patients
ing the face, which may be continuous with exacerbations that demonstrating elevated thresholds on the involved side.267.sI8.612
last for hours to weeks. Some persons can have a transient form Additional studies are required in this area to further document
with numbness beginning in one division of the trigeminal objective sensory loss.
nerve and spreading to include the entire face; this may resolve These episodes of trigeminal neuralgia are triggered by vari
in weeks to months.73.279 There is also a form of the disease ous stimuli such as talking, chewing, yawning, or touching spe
where loss of sensation is permanent. 306.416.670 In these more cific areas of the face.287.552 It appears that tactile stimuli are
severe forms of the disorder the maxillary and mandibular divi more effective than noxious input or intense pressure in inciting
sions are more commonly involved with a small number of an incident. Trigger zones are frequently located about the lips,
cases being bilateraL Weakness of the muscles innervated by nasal ala, nasolabial fold, tongue, or nasal mucosa. When the
the motor root can occasionally be observed but this is a rela trigger zones lead to particularly intense pain, some patients
tively rare finding. Loss of sensation can be so profound as to may consume less food or skip personal hygiene measures
contribute to atrophic destruction of the nose. 217 It is not unusual about the head and neck in order to avoid triggering an event.
for taste sensation to also be impaired. The triggering mechanism is quite individual and a thorough
A limited number of histologic examinations in these patients history should be performed to elucidate it.
demonstrate significant loss of cell bodies within the trigeminal In a large population study, an overall annual incidence rate
ganglion associated with profound Wallerian degeneration of of 4.3 cases of trigeminal neuralgia per 100,000 population is
the cell's axonal extensions. 306.4 16,670 Some form of destructive observed. 353 The age-adjusted rate for women is higher than
inflammation is proposed to account for the disruption of the men, 5.9, compared to 3.4 per 100,000. Trigeminal neuralgia is
trigeminal ganglion and its extensions. A number of connective quite rare before the age of 40; however, the incidence increases
tissue disorders have been implicated as causative agents in pa with each subsequent decade.
tients with this disorder and an autoimmune basis postulated. A number of causes have been identified to account for most
This disorder remains a diagnostic puzzle and unfortunately if not all of the cases of trigeminal neuralgia. The most common
defies treatment. The majority of patients appear to tolerate the cause of this disorder is compression of the trigeminal nerve's
loss of facial sensation and associated pain. 310.4 16 It is the physi sensory roots by a deep caudal arterial loop arising from the su
cian's responsibility to pursue a potential diagnosis before rele perior cerebellar artery, occasionally a branch of the anterior in
gating the patient to the "idiopathic" category as there may be a ferior cerebellar artery, and rarely the basilar artery.24.310,554 These
serious lesion responsible for the sensory dysfunction. Also, arterial loops are not aneurysms and the exact mechanism of
once the possibility of a serious disease has been eliminated, pain production in selected individuals is unknown. Local de
contined patient monitoring is necessary for the appearance of myelination associated with an ectopic focus of spontaneous ac
any connective tissue disorders. 259 Primary treatment is directed tivity associated with ephaptic conduction similar to that of
at protecting the cornea from ulceration by instructing the pa hemifacial spasm (see below) is attractive but remains specula
tient to wear glasses with side shields, observe for corneal le tive.220 Additional causes of trigeminal neuralgia include tumors,
sions and notify a physician should they develop, and use venous compression, arteriovenous malformations, multiple
commercially available eyedrops. sclerosis, hydrocephalus, Paget's disease of the skull, and no
doubt other etiologies as well. Obviously, a complete medical
Trigeminal Neuralgia assessment is mandatory in patients presenting with trigeminal
Trigeminal neuralgia is rather characteristic and relatively neuralgia. The development of powerful anatomic imaging tech
easy to diagnose clinically. Patients usually complain of brief niques, particularly using various types of magnetic resonance
paroxysms of intense unilateral (rarely bilateral) facial pain imaging, continue to better delineate the exact vessel location
likened to a stabbing electric shock or profound burning local and degree of neurovascular compression.391.437.438.113 These
ized to either the maxillary or mandibular divisions of the imaging studies have greatly aided in the diagnosis as well as
trigeminal nerve with occasional involvement of more than one surgical intervention in many patients with trigeminal neuralgia.
division. 24,287,310 Pain may spread from one to any of the other Additionally, other anatomic causes of trigeminal neuralgia can
trigeminal divisions over time. The pain may initially start in be determined by appropriately delineated imaging studies. 324
the mouth region and spread toward the ear or begin about the Symptomatic treatment of trigeminal neuralgia can be ac
tragus and remain there for years until spreading. Also, pain complished with the use of carbamazepine in about 60-79% of
may begin in the orbit or superior dental region and spread to patients.292.70S,768 The problem with this form of treatment is that
the nose/cheek junction or to the outer canthus of the eye. The the medication can lose its effectiveness within several years.
duration of the painful episodes may be as brief as a few sec Other medications such as phenytoin, cionazepam, and baclofen
onds or crescendo from several less intense episodes to last up may be tried but are less effective.129.I40.210 Gabapentin may be
to several minutes. Painful paroxysms tend to occur in periods of assistance in some patients with an idiopathic form of this
lasting on average 49 days, but can last from 1-1462 days.353 disorder, but further trials are needed,659 A number of ablative
These periods tend to recur over a rather varied time courses surgical procedures have been devised. In skilled hands mi
from less than 1 year to multiple recurrences over a year. crovascular decompression of arterial loops or decompression
Occasionally patients with trigeminal neuralgia may experience of the trigeminal ganglion itself appears to offer significant pain
coincident hemifacial spasm on the involved side, in which case relief in the vast majority of patients.21 1.264.382,415.490,577,6(}4,644,682,690.694
the disorder is referred to as tic convulsif or tic douloureux, Thermocoagulation has also been demonstrated to offer results
which may respond well to surgical microvascular decompres similar to those of microvascular decompression. 668 Further
sion. 316,605 Physical examination in these patients often fails to study is necessary to determine the optimal intervention for this
reveal any objective abnormalities regarding alterations in disconcerting disorder.
660 - PART IV CLINICAL APPLICATIONS
Electrophysiologic Evaluation and Findings nervous system compromise not involving the motor nucleus
There are a limited number of relatively routine electrophysi can only result in poor activation of voluntary motor units, One
ologic techniques that can be used to assess trigeminal nerve case of typical trigeminal neuralgia with no identifiable cause
function. A number of less routine techniques employing silent produced abnormal spontaneous activity in the temporalis
periods can also be used but are not discussed here. Various pit muscle;618 however, this is likely to be a rare finding noted in
falls of the electrophysioiogic evaluation of trigeminal nerve profound and progressive disease with significant comprol!1ise
dysfunction are discussed at the end of this chapter. of the root exit zone for the motor segment of the mandibular
division. Rarely, myokymia may be noted in the masseter
Sensory Conduction muscle associated with brainstem tumors affecting the fifth cra
It is possible to perform a pure sensory nerve conduction nial nerve. 344 One case of neuromyotonia following radiation
through indirect means of the supraorbital nerve. The supraor has been reported. 447 It is possible to also detect hemimastica
bital nerve can be activated at the supraorbital notch and at a tory spasm of the masseter muscle, which appears similar to
second site along the supraorbital nerve toward the skull's hemifacial spasm (see below).699 The needle electromyographic
vertex while recording from the orbicularis oculi muscle, i.e., a examination simply reveals a crescendo/decrescendo firing of
blink reflex from two stimulation sites. 325,639 The Rl latency motor unit action potentials during the clinically observed
from the supraorbital notch is subtracted from the second site spasm that occur spontaneously and are not under voluntary
and this time is divided into the distance between activation control.
sites. Needless to say, this technique has limited applications to In patients receiving radiation to the head and neck region,
possible peripheral lesions but may be of assistance for research post-irradiation neuromyotonia has been reported in muscles in
purposes in fiber diameter and velocity investigations regarding nervated by both the facial and trigeminal nerves. 441
the afferent pathways of the blink reflex.
Masseter Reflex Oaw JerklJaw Reflex)
Motor Nerve Conduction There are no direct routine ways of electrically stimulating
There are no routine motor nerve conduction studies avail the motor division of the fifth cranial nerve and recording an en
able for evaluating the trigeminal nerve's motor component. suing CMAP from the masseter or temporal is muscles. One can
However, it is possible to record a surface CMAP from the use intracranial stimulation to generate a direct mMseter muscle
mylohyoid muscle following intraoral activation of the mylo CMAP as well as an H-reflex, but this not routinely per
hyoid nerve. IS8 A pediatric stimulator secured to a tongue de formed. 133 ,134.23o It is possible to record a CMAP from the mas
pressor is positioned in the pterygomandibular space (region seter muscle through indirect means by taking advantage of the
between the medial pterygoid muscle and mandibular ramus). jaw jerk/jaw reflex or masseter reflex. 236,388 This response can
A mean CMAP onset latency of 1.9 ms (upper limit 2.3 ms) be facilitated through gentle voluntary contraction of the mas
was documented with a mean amplitude of 4.9 mV with a seter and forceful contraction of other muscles. 269 Initiating an
lower limit of 1.3 mY. The side-to-side latency difference was electrophysiologic instrument's sweep as a reflex hammer taps
found to be 0.0 ± 0.2 ms with an upper limit of 0.4 ms. An av the patient's jaw results in contraction of the masseter muscle
erage side-to-side amplitude difference of 2.2 m V was docu bilaterally. Locating an active recording electrode over the mas
mented. It is also possible to study the deep temporal nerve seter muscle allows one to record the electrical activity associ
while recording from the temporalis muscle; however, the re ated with this reflex response and measure the muscle's CMAP
sponse was obtained bilaterally in only 60% of control sub onset latency and compare both sides objectively, which is a dis
jects. Using the mylohyoid nerve technique, it is possible to tinct advantage over the pure clinical response. The afferent
record a late response from the mylohyoid muscle. 159 The clin limb of this response conveying proprioceptive impulses from
ical value of this late response as well as the direct CMAP re the masseter muscle most likely traverses the mandibular divi
mains to be determined in patients with disorders amenable to sion through the trigeminal ganglion to reach their cell bodies in
this nerve conduction technique. the mesencephalic nucleus, which then travel to and synapse
with the motor nucleus cells in the pons. 191 .533 The efferent limb
Needle Electromyography of the response exits the motor nucleus to reach the muscle via
Needle electromyographic evaluation of the trigeminal nerve the motor roots through the mandibular division. This pathway
is relatively straightforward as only one portion of the trigemi allows one to investigate both central and peripheral damage to
nal nerve, mandibular division, is assessed. Also, only two mus the fifth nerve. Onset latencies to the CMAP are quite variable
cles are routinely examined and they are easy to locate: the between individuals (7.6 ± 1.6 ms; 6.4-9.2 ms) and side-to-side
temporalis and masseter muscles. These muscles are evaluated differences in the same patient are more helpful when a unilat
just as any other skeletal muscle. Both spontaneous and volun erallesion is present (0.07 ± 0.15 ms; difference> 0.5 ms, or
tary activity are examined. Membrane instability denotes a absent response is considered abnormal).641 This reflex is elec
lesion of the mandibular division at some location from the trically present in all persons under the age of 70 years. In per
motor nucleus in the brainstem to the muscle innervated. sons over 70 years of age, an absent response cannot be
Relaxation can occasionally be difficult, but having the patient considered pathologic but a side-to-side difference may be of
forcefully bite and then relax with the jaw falling somewhat significance.
posterior usually suffices to produce adequate electrical silence. The primary reason for using the masseter reflex in most clin
Mandibular nerve trauma secondary to facial fractures or space ical settings is to evaluate patients with facial pain. Clinically,
occupying lesions that have resulted in axonal loss of the motor the concern is to differentiate between trigeminal neuralgia due
fibers generate membrane instability in these muscles. 161,530,618 to vascular compression or the so-called idiopathic form from
The needle electromyographic examination is typically facial pain secondary to more ominous etiologies such as pri
normal in trigeminal neuralgia resulting from root entry zone mary tumors or metastatic disease. 368.530 Generally, the masseter
vascular lesions of the small arterial branch type, Also, central reflex is typically abnormal in space-occupying lesions such as
Chapter 17 FOCAL CRANIAL NEUROPATHIES - 661
tumors or cavernous sinus vascular malformations, or traumatic the idiopathic or root entry zone form of trigeminal neuralgia
injuries affecting the trigeminal nerve's afferent fibers convey due to vascular loops, the blink reflex is characteristically
ing the reflex. Central lesions such as multiple sclerosis can also normal, although rarely the Rl and R2 response latencies may
produce abnormalities of this reflex. 237•531 •762 In persons with the be mildly prolonged in long-standing disease. 134.136,36S.530 An in
vascular type of root entry zone compression causing trigeminal teresting caveat regarding trigeminal neuralgia not arising from
neuralgia, the masseter reflex is normal. The masseter reflex readily apparent causes is that the ophthalmic division is in
and blink reflex (see below) are complementary as they exam volved significantly less often than the maxillary or mandibular
ine different portions of the trigeminal nerve. It is important to divisions, yet the blink reflex only optimally evaluates the oph
recognize that only stimulating the supraorbital nerve when thalmic division. It is certainly possible to elicit a blink reflex
eliciting the blink reflex ignores the other two divisions of the by stimulating the peripheral divisions of the maxillary (infra
trigeminal nerve, thus potentially missing focal lesions. The orbital nerve) and mandibular (mental nerve) divisions to
masseter reflex is a reliable method of assessing the mandibular assess these pathways. Unfortunately, a blink reflex cannot
portion of the trigeminal nerve. When an abnormality of this always be obtained in normal individuals when stimulating
reflex is documented, needle electromyography of the tempo these nerves, whereas the supraorbital nerve always results in a
ralis and masseter muscles can help differentiate a lesion affect blink reflex in normal persons. 214 The obvious problem in pa
ing preferentially the afferent or efferent pathway. If positive tients with trigeminal neuralgia is that infraorbital/mental
sharp waves and fibrillation potentials are noted in these mus nerve stimulation can yield an absent response, but this may
cles, then at least the motor division is involved. Of course, not necessarily indicate pathology. An absent response unilat
there are shortcomings to this technique, particularly when in erally with activation of these two nerves is suspicious, but in
vestigating central nervous system lesions. There are fewer ab sufficient numbers of normal persons have been studied to
normalities of the masseter compared to blink reflex, most determine the unilateral absence of either R 1 or R2 with re
likely because of the comparatively simpler pathway and fewer spect to a significance level. The results of surgery can also be
connections of the masseter reflex. assessed with respect to the degree of neural dysfunction pre
sent prior to surgical intervention. 135
Blink Reflex In persons with idiopathic trigeminal sensory neuropathy
The blink reflex can be an excellent electrophysiologic tech the masseter reflex can be expected to be absent or markedly
nique for investigating lesions of the trigeminal nerve. Recall delayed on the affected side or bilaterally absent if the patient
that the afferent pathway for this reflex is the supraorbital nerve, has a problem on both sides.35.291 The blink reflex demonstrates
while the efferent segment is the facial nerve. When performing the expected findings of an afferent problem. Specifically, when
the blink reflex it is necessary to record from both orbicularis stimulating the involved supraorbital nerve, RI is either
oculi muscles for each activation of the supraorbital nerve, and markedly prolonged or absent as is the ipsilateral and contralat
to study these responses bilaterally. The ipsilateral RI provides eral R2. Activating the uninvolved side results in normal re
information regarding any potential lesions of the fifth and sev sponses for both R 1 and the bilateral R2s. If the patient has
enth nerves on the side of stimulation while the bilateral R2 bilateral disease, absent or delayed ipsilateral Rl and bilateral
waveforms allow further insight into a lesion affecting the supra R2 responses can be anticipated for either left or right supraor
orbital or facial nerves. For example, a supraorbital nerve injury bital nerve stimulation. Needle electromyography should be
generates a prolonged RI ipsilaterally as well as prolonged R2 completely normal in persons with this disorder. The masseter
waveforms both ipsilaterally and contralaterally. On the other inhibitory reflex or silent period is also abnormal in these pa
hand, a prolonged Rl and R2 ipsilateral to the stimulation, but a tients,35 This technique simply measures the length of electrical
normal R2 contralaterally implies that the efferent (facial nerve) silence following a tap on the chin during active contraction of
and not afferent (supraorbital nerve) pathway is affected. If an the masseter muscle and is primarily an experimental technique
absent R 1 is noted ipsilateral to the stimulation site with normal at this point.
bilateral R2s, the lesion most likely involves the principal sen The blink reflex can also demonstrate abnormalities in pa
sory nucleus or the neural fibers just leading into or exiting this tients with various types of demyelinating peripheral polyneu
region of the brainstem. It is always necessary to also examine ropathies. Persons with diabetic neuropathy, chronic renal
the direct facial nerve responses when performing the blink failure, Guillain-Barre syndrome, Charcot-Marie-Tooth (CMT)
reflex to examine conduction in the peripheral extracranial por disease, and those exposed to toxins such as trichloroethylene
tion of the seventh nerve, particularly when computing the RID may have RI and R2 findings suggestive of involvement of
ratio (Rllatency "R" divided by the direct facial nerve response either the seventh or fifth cranial nerve. 190,369.375,439,672 Inter
latency "D"). In patients with posterior fossa tumors, either in estingly, the Rl latency is usually abnormal in CMT type I, but
trinsically or extrinsically located, the blink reflex demonstrates mildly abnormal or normal in CMT type II. Blink reflex para
the characteristic abnormalities noted above. 54,174,371,431,596 Similar meters can be used to detect patients with asymptomatic disease
findings can be anticipated in multiple sclerosis365.367.372,508,616 and or follow them serially to assess treatment or the natural course
brainstem strokes of the Wallenberg type where the R2 on the in of the disease with respect to its effect on the cranial nerves.
volved and uninvolved side are abnormal when the nerve on the
affected side is activated. However, stimulation of the unin Trigeminal SEPs
volved supraorbital nerve usually results in a normal R2 bilater Because of the limited methods available to electrophysio
ally, but occasionally an abnormal R2 on the involved side can logically evaluate the trigeminal nerve, somatosensory evoked
be seen in severe lesions. 532,715 potential techniques were developed in the hope of more fully
In patients with facial pain, the blink reflex is a very good assessing possible lesions of the fifth cranial nerve, particularly
test to perform. If an abnormality is detected, there is a distinct in the case of trigeminal neuralgia. The first described techniques
possibility that a peripherally or centrally located space-occu used surface excitation of the upper and lower lips,42,5S.91.195,270.613.678,679
pying or demyelinating lesion is responsible. In persons with skin overlying the infraorbital and mental foramens l65 ,224.231,337
662 - PART IV CLINICAL APPLICATIONS
Nucleus oi tractus Abducens nucleus portion of the trigeminal spinal tract. Depending upon the pres
50litarius ence or absence of these peaks, a lesion is presumed to interfere
with them at the above-specified locations.
Superior
Using the intraforamenal stimulation technique, approxi
mately 50% of patients diagnosed with the idiopathic form of
SPinal) Nucleus
trigeminal neuralgia demonstrated abnormalities of neural «on
trigeminal
duction. In about 71 % of these patients the lesion appeared to
Tract --..,y~..J
be located at the root entry zone by the specific alteration of one
Nervus
of the recorded waveforms. 414 In persons with tumors at the base
of the skull producing trigeminal symptoms, 100% had abnor
mal trigeminal SEPs. This technique does require the placement
of fine needle electrodes directly into the neural foramen in
order to achieve activation of a substantial portion of the periph
eral nerve trunk and avoid undesired artifacts. Despite the rather
promising results of these studies in mUltiple pathologic states,
further substantiation of this particular technique is required by
other investigators prior to accepting this method as the proce
dure of choice. especially since far-field and not near-field po
'vlotor root tentials are used for measurement purposes. The difficulty with
using far-field potentials is their uncertain utility in clinical
Figure 17-3. Facial nerve component in the pons. The motor pathology; further experience is required in this respect.
fibers loop around the abducens nucleus whereas the sensory and su
perior salivatory fibers form the nervus intermedius. (From Barr ML,
Kiernan jA:The Human Nervous System:An AnatomicalViewpoint, 5th FACIAL NERVE
ed. Philadelphia.J.B. Uppincott. 1988, with permission.)
ANATOMY
or oral gingiva,56.57.58 and subcutaneous stimulation of nerve
over the two above-noted foramens.610.657 These methods The facial or seventh cranial nerve consists of both motor
demonstrated abnormalities in about 41 % of patients with idio and sensory components and pursues a rather intricate course as
pathic trigeminal neuralgia and all patients with trigeminal neu it supplies various structures in the head and face. The facial
ralgia due to identifiable causes such as tumors or vascular motor nucleus is located in the distal third of the ventrolateral
anomalies of the carotid artery.679 This method of eliciting SEPs aspect of the pons tegmentum. Motor fibers arising from this
initially appeared to be a promising technique with an ability to nucleus form a compact bundle as they initially travel toward
diagnose pathology not only in trigeminal pain syndromes from the floor of the fourth ventricle to loop around the abducen's nu
readily detectable lesions, but also in the type due to microvas cleus (internal genu) from a medial to lateral position (Fig. 17
cular compression of the root entry zone. Further study has cast 3). These fibers then head toward the seventh nerve nucleus,
significant doubt on the validity of surface induced trigeminal again between it and the nucleus of the spinal trigeminal tract,
SEPs (see below). to emerge from the ventral portion of the pons between the
These techniques were severely criticized for providing an vestibulocochlear nerve and the nervus intermedius (see below)
insufficient stimulus to be recorded from the somatosensory about the cerebellopontine angle. The facial nerve, along with
cortex with respect to background noise. The use of fine needle the nervus intermedius and vestibulocochlear nerve, passes
electrodes placed into the supraorbital, infraorbital, and mental from the brainstem region into the temporal bone through the
foramen in awake and anesthetized patients clearly demon intemal auditory meatus (Fig. 17-4). At the fundus of the inter
strated that the previously presumed cortical potentials were nal auditory meatus, the facial nerve enters the petrous portion
most likely a result of stimulus artifact, local muscle twitch arti of the temporal bone and traverses this structure in a serpentine
fact, and volume-conducted blink reflex artifact averaged into a course through the facial canal. The nerve first travels laterally
small and variable cortical response. 136.406-414 in a region between the semicircular canals and cochlea. This
When the previously described methods of stimulating sub aspect of the facial canal is referred to as the labyrinthine seg
cutaneously or cutaneously over the lips, gums, and various ment; it is the narrowest part of the facial canal in that the nerve
foramens were performed on anesthetized patients, the pre takes up approximately 83% of the available space. In the vicin
sumed cortical and subcortical potentials could not be recorded, ity of the tympanic membrane, the nerve abruptly turns posteri
suggesting that they were indeed due to time-locked artifacts. orly and runs a horizontal course, thus accounting for this
Care was taken to demonstrate that the anesthesia did not ac portion of the factal canal to be known as the tympanic or hor
count for the disappearance of the potentials. Directly activating izontal segment.465 The region of an abrupt change in direction
the supraorbital, infraorbital, or mental nerves within their re is called the geniculum, where the geniculate ganglion is lo
spective foramens, however, yields stable and reproducible cated. This aspect of the facial nerve is also known as the exter
waveforms as recorded with a far-field or noncephalic referen nal genu as opposed to the previously noted internal genu. Near
tial montage (skull vertex referenced to C7) in order to assess the mastoid air cells, the facial nerve changes direction to pro
the neural pathway prior to the nerve impulse entering the brain ceed in a vertical direction toward the stylomastoid foramen.
stem, as well as arrival at the somatosensory cortex. Three dis Another name for this aspect of the facial canal is the mastoid
tinct peaks, an initial positive and two subsequent negative or vertical segment. Upon reaching the stylomastoid foramen,
peaks, are believed to arise from the neural impulse's entry into the facial nerve exits the skull to supply the muscles of facial
the Gasserian ganglion, root entry zone, and the presynaptic expression.
Chapter 17 FOCAL CRANIAL NEUROPATHIES - 663
Figure '1-4. Facial nerve. The facial nerve pursues a rather serpentine course throughout its intratemporaJ passage to reach the stylomastoid
foramen. (From May M:The Facial Nerve. New York, Thieme, 1986, with permission.)
In addition to the motor fibers. (special visceral efferents) subadjacent nucleus of the spinal tract Special visceral affer
arising from the motor nucleus of VIT, general visceral effer ent or gustatory (taste) fibers originate primarily along the lat
ent parasympathetic fibers also take origin from the superior eral margins of the anterior two-thirds of the tongue (Fig. 17-5).
salivatory and lacrimal nuclei that lie medial to the pontine They then traverse the lingual branch of the mandibular nerve to
motor nucleus (Fig. 17-3). Fibers from these two nuclei exit the join the chorda tympani nerve. The gustatory fibers follow the
brainstem through the nervus intermedius. The nervus inter facial nerve to the geniculate ganglion where their cell bodies
medius travels with the facial nerve as a separate nerve until are located. The central projections of the taste fibers enter the
reaching the geniculum, where it fuses with the main trunk of central nervous system through the nervous intermedius to then
the facial nerve to form the geniculate ganglion. From the traverse the tractus solitarius to the nucleus of this tract and
geniculate ganglion. the general visceral efferent fibers pursue eventually reach the cortical area for taste posterior to the sen
two separate courses. One set of fibers exits the facial nerve at sory region of the mouth.
the level of the geniculate ganglion by way of the large or
greater petrosal nerve to synapse in the pterygopalatine gan NEURAL BRANCHING
glion and then supply the lacrimal gland and glands of the nasal
mucosa (Fig. 17-5). The second set of fibers continues with the Of particular importance for the electrodiagnostic medicine
main facial nerve trunk until reaching the chorda tympani, examination is a working knowledge of the neural branching of
where they depart through the latter nerve and synapse in the the facial nerve. The first of two braches arising in the facial
submandibular ganglion. Postsynaptic fibers then supply the canal is to the stapedius muscle (Fig. 17-5). This nerve branch is
submandibular and sublingual glands. given off behind the posterior wall of the tympanic cavity and
Two major classes of afferent fibers are contained in the sev reacbes the stapedius muscle through a small canal. Ap
enth nerve. General somatic afferent fibers conveying cuta proximately 6 mm proximal to the stylomastoid foramen, the
neous sensibility from the external surface of the tympanic chorda tympani nerve departs the facial nerve and travels in its
membrane, wall of the external acoustic meatus, small region own canal to perforate the posterior wall of the tympanic cavity
posterior to the ear, and concha of the auricle join the facial and eventually join the lingual nerve.
nerve in the immediate vicinity of the stylomastoid foramen After exiting the stylomastoid foramen, the facial nerve lies
(Fig. 17-5). These fibers traverse the facial nerve to reach their in the substance of the parotid gland and forms a complex net
cell bodies located in the geniculate ganglion to then enter the work of facial nerve branching to innervate the various facial
brainstem through the nervus intermedius. The fibers continue muscles. The posterior auricular nerve ascends anterior to the
in the spinal tract of the trigeminal nerve to terminate in the mastoid process and joins with a branch from vagus nerve, i.e.,
664 - PART IV CLINICAL APPLICATIONS
Glands
of nasal
mucota
Geniculate _ _-¥l_-I:
gan&lion
Chorda
typmani
nerve
Submandibular
gland Branches to
facial
muscles
To skin of
extemalear
(with vagus)
Figure '7-5. Afferent and efferent fibers in the facial nerve. Topographic testing attempts to take advantage of the sequential origin of the
various branches (see text). (From Barr ML. Kiernan JA:The Human Nervous System:An AnatomicalViewpoint, Sth ed. Phiiadelphia,J.B. Lippincott,
1988. with permission.)
the auricular nerve. A communication is fonned with the great division penetrates the inferior margin of the parotid gland to
auricular and lesser occipital nerves. The muscles supplied by pierce and innervate the platysma muscle.
this nerve are the posterior auricular and intrinsic muscles on
the auricle's cranial aspect. A digastric brancb originates in FOCAL FACIAL NEUROPATHIES
close proximity to the posterior auricular nerve to innervate the
posterior belly of the digastric muscle. The stylohyoid branch Facial nerve compromise is likely to be the most commonly
then arises to innervate the stylohyoid muscle. After this nerve encountered cranial neuropathy. There are in excess of 80 dis
branch is given off, the nerve enters the substance of the parotid tinct etiologies of focal seventh nerve compromise described in
gland to fonn its tenninal branches. the medicalliterature. 468 The majority of these different causes
The most superior of the terminal facial nerve branches is the
temporal division, which crosses the zygomatic arch to the
temple region (Fig. 17-5). In this area, the nerve supplies the an Table 17-1. Etiology of Facial Nerve Disorders
terior and superior auricle muscles. It then continues to inner Etiology % of Patients
vate the frontalis and orbicularis oculi muscles. The next Bell's palsy (idiopathic) 57
inferior branch of the facial nerve is the zygomatic division,
which crosses the zygomatic bone to reach the eye's lateral can Trauma 17
thus and also innervate the orbicularis oculi. The buccal divi Herpes zo~ter cephalicus 7
sion courses relatively horizontal and further subdivides into the Tumor 6
upper deep branches to supply the procerus, zygomaticus
Infection 4
major, levator labii superioris, levator anguli oris, zygomaticus
minor, levator labii superioris alaeque nasi (shortest muscle Birth (congenital/acquired) 3
with the longest name in the body), and the small nasal ala mus Hemifacial spasm 2
cles. The lower deep branches innervate the buccinator and or Other 2
bicularis oris muscles. A mandibular division travels inferior
to the mandible's angle deep to the platysma muscle, but superli Central nervous system
cial to the digastric muscle and then reaches the deep surface of Questionable
the depressor angUli oris muscle. This nerve supplies the risorius Etiology of facial nerve dysfunction from 1575 patients examined over 20 years.
muscle and those subserving lower lip depression. The cervical Modified from May M:The Facial Nerve. NewYork,Thieme. 1986.
Chapter 17 FOCAL CRANIAL NEUROPATHIES - 66S
are relatively rare with most of the more common facial neu Table 17-2. Onset of Facial Paralysis in Order of
ropathies confined to a small number (Table 17-1). Clearly the Frequency of Occurrence
Table 17·3. Combination Syndromes of Cranial Nerves IX, X, XI, and XII
Cranial Nerves Lesion Syndrome
IX,X,XI Glomus tumor; lymphatic metastasis; chordoma; tumor of the ear, Vernet's Qugular foramen)
nose, or throat; neurinoma
X (ambiguous nerve) or Brainstem vascular insult; tumors Avellis' {palatolaryngeal
Accessory Branch (X) of XII hemiplegia}
X-XI Trauma; brainstem vascular insult Schmidt's (scapulolaryngeal
hemiplegia)
X (inferior ganglion) XI and XII Trauma; brainstem vascular insult jackson's (glossopalatolaryngeal
hemiplegia)
IX,X,XI,XII Ear, parotid gland, skull base tumors; adenopathies; aneurysm of the Collet-Sicard
carotid artery; neck cellulitis
IX, X, XI, XII (cervical Parotid gland, posterior, nasal, lymph node tumors; lymphosarcoma; Villaret's
sympathetic) pharyngeal abscess
X (distal to inferior ganglion), XII Parotid gland tumor, trauma Tapia's (glossolaryngeal
Modified from Andrioli G, Rigobello L, Mingrino S, et al; Tapia's syndrome caused by a neurofibroma of the hypoglossal and vagus nerves. J Neurosurg
1980;52;730-732, and Roger J. Bille J.Vigouroux RA: Multiple cranial neuropathies. In Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology,Vol 2.Amsterdam.
North-Holland Pub. Co., 1969.
the lesion to the region of the nerve between the nerve to the and improve rather rapidly. A category of idiopathic cranial
stapedius and chorda tympani nerve. Despite the relative popu polyneuropathy can involve any of the cranial nerves, is almost
larity of these tests, they are all subject to a number of shortcom always associated with a constant and profound pain in the tempo
ings and their utility with respect to diagnostic localization and ral or periorbital region, resolves in less than 12 weeks, and the
prognostication have been questioned. 176,215,453,465 pain responds well to corticosteroid administration within 48
Magnetic resonance imaging with and without gadolinium hours. 51 .300,342.385.570,673.687 Cranial nerves most frequently involved
enhancement has been used to image the facial nerve in pa in this disorder are III, V, and VI, with occasional dysfunction of
tients with Bell's palsy. 144,393.400.502.503.631,702.755 The facial nerve IV, VII, VIII, IX, X, XI, and XII. This syndrome of idiopathic cra
characteristically demonstrates an increased signal intensity, nial polyneuropathy is very similar to Tolosa Hunt syndrome
particularly within the facial canal. Persons with enhanced sig (cavernous sinus disease characterized by retro-orbital pain ac
nals in the mastoid segment tend to have less than satisfactory companied by dysfunction of the third, fourth, and sixth cranial
recovery; however, this has not been verified by all studies. An nerves) and further work is required to expand on this
increased signal uptake with the use of gadolinium confirms issue.121,313.314,319,664.6&4.719 Also, it is possible that the idiopathic form
the presence of inflammation about the facial nerve in Bell's of polycranial neuropathy may be a variant of Guillain-Barre syn
palsy. Although the use of MRI is not likely to be helpful in drome with preferential involvement of the cranial nerves,342.499
predicting outcome, it is of most value in documenting the ab Some of these patients have elevated cerebrospinal fluid proteins
sence of soft tissue masses, particularly in atypical cases of with generalized areflexia. A small number of patients with sar
facial paralysis presumed to be Bell's palsy. In these instances, coidosis and herpes zoster/simplex infections can present with
the addition of computed tomography (CT) may be of help in multiple cranial neuropathies. 4•11 •434 It is also necessary for the
defining bony deformities, especially in cases of trauma. Of practitioner to consider various types of tumors and vascular mal
particular interest is that a number of patients demonstrated en formations or infarctions as a cause of multiple cranial nerve dis
hanced uptake of the facial nerve in the cerebellopontine angle orders, especially when symptoms do not subside within 3
and brainstem regions. 335,393,400 months.22,586 Commonly, although not exclusively, the lower four
The finding of possible brainstem involvement in Bell's palsy is or five cranial nerves are affected, progression is typical, and
important in that it supports the clinical and electrophysiologic ob steroids may help with the pain but do not assist in resolution of
servations of multiple cranial nerves being affected in this disor neurologic deficits, suggesting a more ominous type of lesion
der. A number of studies have documented some form of (Table 17-3). Suffice it to say that a thorough history and physical
dysfunction in the distribution of the optic, trigeminal, vestibulo examination in combination with electrical and imaging studies
cochlear, and glossopharyngeal nerves.6.271.393,572 This occurrence, should always be pursued when a patient suspected of having
if substantiated by further studies, is most likely a result of a some Bell's palsy is seen with an atypical presentation or clinical course.
what localized process affecting multiple cranial nerves in the As noted above, the causative agent in Bell's palsy is not fully
region of the seventh nerve with preferential involvement of the defined, thus justifying this disorder's designation as an idio
facial nerve because of its confinement in a long and rigid bony pathic facial palsy. Both viral agents and autoimmune dysfunc
canal. The involvement of multiple cranial nerves associated with tion have been postulated as etiologies for Bell's palsy, with viral
Bell's palsy is somewhat different than a number of other types of etiologies receiving a renewed interest. 496 Despite an ill-defined
disorders in which multiple cranial nerves are affected. In primary etiology, there is general agreement as to the pathophysiology of
Bell's palsy, the major disorder manifested is preferential facial facial nerve dysfunction. The facial nerve demonstrates an in
nerve dysfunction with mild to moderate patient complaints sug crease in intraneural fluid, which causes the nerve to swell along
gestive of some lack of function in the fifth or eighth and rarely a significant portion of its longitudinal extent. 36.39,77.293.397.519
ninth cranial nerves. These symptoms are usually nonprogressive Within the tight confines of the facial canal, particularly the
Chapter 17 FOCAL CRANIAL NEUROPATHIES - 667
narrow labyrinthine segment that has the most tenuous blood the various facial nerve branches and muscles innervated, An
supply, neural and vascular compression may ensue. This com intratemporal lesion occurs between the internal auditory
pression begets further edema resulting in a cyclical pattern with meatus and the stylomastoid foramen. Finally, the intracranial
the net result being neural dysfunction associated with a patho segment of the facial nerve lies between the nerve's exit from
logic spectrum of electrophysiologic abnormalities of conduc the brainstem to the point where it enters the internal auditory
tion block, demyelination, and axonal loss. The junction meatus.
between the internal auditory meatus and the labyrinthine seg Extracranial Injuries. The facial nerve is usually injured
ment is believed to be the location of greatest neural compromise about the region of the parotid gland; however, the main nerve
because of a constricting ligament and canal size differential trunk as it exits the stylomastoid foramen, or selective terminal
leading to a damming ofaxoplasmic flow and the above-noted branches distal to the parotid gland can also be damaged. Some
neural reactions.182.183,2oo,758 form of penetrating trauma such as glass shards, knife wounds,
When considering the most appropriate therapeutic interven orthognathic surgery, or gunshot wounds are common injury
tion, it is necessary to first consider the natural course of pa mechanisms.123.338,685 A surgical procedure that can cause facial
tients with Bell's palsy. In an investigation of 1011 persons with nerve injury is carotid endarterectomy. 163,440,740 Blunt trauma to
Bell's palsy who were followed for 1 year in which neither sur the extracranial portion of the facial nerve can occur secondary
gical nor medical treatment was provided, a number of interest to motor vehicle accidents, falls, or fist fights. In clean facial
ing findings were noted. 478,553 Of all patients evaluated, 84% had lacerations, immediate repair of the nerve is recommended. 3,714
a return offunction graded as normal. The remaining 16% of When there is moderate to significant wound contamination, the
patients had moderate to severe sequelae that included facial nerve's ends should be tagged and the wound irrigated, de
weakness, associated movements of facial muscles other than brided, and either closed or left open for delayed closure. Once
those desired (synkinesis), hemifacial spasm, and facial muscle a clean and acceptably vascularized wound site is achieved, an
contractu res. With respect to improvement, 85% of patients end-to-end repair is recommended if possible. This procedure
demonstrated some return of function within the first 3 weeks of can be delayed up to 3 weeks with as good results as immediate
onset. anastomosis. Freeing the nerve ends proximally and distally
Prior to formulating an appropriate treatment plan, an accu may be necessary to achieve more nerve length. Nerve grafting
rate diagnosis of the lesion' s magnitude and completeness is considered only when insufficient facial nerve exists to per
should be determined and a prognosis arrived at. The best form an end-to-end repair, The greater auricular nerve is consid
quantitative method available for accomplishing both of these ered the nerve of choice for facial nerve grafting procedures.
goals is electrophysiologic testing. In persons who have up to Nerve repair is only performed once the diagnosis of neural
90% axonal loss as determined by the electrodiagnostic medi transection is made. In open injuries, exploration can identify
cine evaluation, conservative treatment is the most appropriate this circumstance. Closed injuries should be evaluated both
course of action. This type of therapeutic intervention consists clinically and electrophysiologically to determine the extent of
of first the application of an eye patch if necessary to protect nerve injury, It may be necessary to delay this type of complete
the patient's cornea and keep the eye from drying out. Also, evaluation for several days if warranted by the patient's medical
most persons are given a short course of high-dose corticos condition or if there is significant swelling about the mandibular
teroids. A number of studies showed no demonstrable differ region. As noted above, there is little difference in outcome
ence between the patients taking and not taking corticosteroids. within the first 3 weeks with respect to neural repair.
Disagreement continues regarding this subject; however, in Intratemporal Injuries. Motor vehicle accidents are the
persons in whom corticosteroids are not contraindicated. a trial most common cause of intratemporal facial nerve injury result
mayor may not help alter the course of the disease but most ing from temporal bone fractures. Additional inciting incidents
likely is not deleterious, helps any pain present, and may of facial nerve insult in this region are unavoidable or inadver
reduce the extent of denervation. 8 Until there is general agree tent surgical severance of the nerve, blunt trauma, and penetrat
ment as to the most appropriate course of action, the use of cor ing injuries of the cranium. 98,28t,347.630 Temporal bone fractures
ticosteroids will continue in the hope of positive effects. In are typically classified as either longitudina