Pub - Localization in Clinical Neurology PDF

Authors:
Brazis, Paul W. ; Masdeu, Jose C. ; Biller, Jose

T itle: Local i zati on i n Cl i ni cal Neurol ogy, 5th Edi ti on
Copyright ©2007 Lippincot t Williams & Wilkins
> Fr ont of B ook > Author s
Authors
Paul W. Brazis MD
Prof essor of Neurol ogy
Department of Neurol ogy, Mayo Medi cal School ;
Consul tant i n Neurol ogy and Neuro-O phthal mol ogy,
Mayo Cl i ni c Jacksonvi l l e, Jacksonvi l l e, Fl ori da
Jose C. Masdeu MD, PhD

Prof essor and Di rector
Neurosci ences, Uni versi ty of Navarra Medi cal School , Pampl ona, Spai n
José Biller MD, FACP, FAAN, FAHA

Prof essor of Neurol ogy and Neurol ogi cal Surgery; Chai rman
Department of Neurol ogy, Loyol a Uni versi ty Chi cago, Stri tch School of
Medi ci ne, Chi cago, Il l i noi s
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Authors: Brazis, Paul W. ; Masdeu, Jose C. ; Biller, Jose
Copyright ÂŠ2007 Lippincot t Williams & Wilkins
> Fr ont of B ook > D edic ation
Dedication
To the memory of Dr. Frank A. Rubi no, who taught us the val ue of l ocal i zati on
and a cari ng approach to neurol ogi cal pati ents
> Fr ont of B ook > P r efac e to the Fifth E dition
Preface to the Fifth Edition
The f our previous edit ions of t his book w ere w ell received by readers and w e
are grat ef ul f or t heir posit ive comment s. Reading t hrough t he pref aces of t he
f our previous edit ions, much of w hat w as said t here st ill holds. How ever, recent
years have seen import ant and st eady advances in nearly all aspect s of
neurology. Physicians responsible f or t he care of pat ient s w it h neurologic
disease conf ident ly manage common and unf amiliar condit ions assist ed by a
syst emat ic and organized adherence t o an int elligent use of algorit hmic
clinicoanat omic mat rixes.
This new edit ion of Local i zati on i n Cl i ni cal Neurol ogy is again w rit t en f or
“f ront line” clinicians w ho are daily conf ront ed w it h t he “Where is it ?” of
neurologic disorders. The chapt ers have been updat ed and mult iple new chart s
have been added t o help w it h t he diff erent ial diagnosis of a variet y of neurologic
f indings and disorders. We again hope t his edit ion w ill help t he clinician t o
diagnose pat ient s w it h great er accuracy and w it h t he least cost f rom
unnecessary t est ing.
We w ould like t o dedicat e t he 5t h edit ion of Local i zati on t o t he memory of one of
t he people w ho inspired t his book, Dr. Frank A. Rubino, a superb neurologist
w ho t aught us t o value localizat ion in clinical pract ice.
We w ould like t o t hank our colleagues at t he Mayo Clinic in Jacksonville,
Scot t sdale, and Rochest er; at t he Universit y of Navarra; at Loyola Universit y
Chicago, and at I ndiana Universit y. O ur grat it ude goes in part icular t o t he
f ollow ing individuals: Drs. Neil R. Miller, Andrew G . Lee, Jonat han D. Trobe,
James J. Corbet t , Rohit Bakshi, Marí a A. Past or, John Mazziot t a, Mark L.
Dyken, William E. De Myer, and James F. Toole. We especially t hank Frances
DeSt ef ano and Scot t Scheidt of Lippincot t Williams & Wilkins f or t heir
encouragement , edit orial eff ort s, and prof essionalism. As alw ays, t he const ant
support and encouragement of f amily and f riends are appreciat ed.
Paul W. Brazis
Jose C. Masdeu
José Biller
> Fr ont of B ook > P r efac e to the Four th E dition
Preface to the Fourth Edition
Since t he last edit ion of t his book, t he many discoveries brought about by
f unct ional neuroimaging and ot her t echnologies have sharpened our know ledge of
localizat ion in t he nervous syst em. These development s are ref lect ed in t he
present edit ion, w hich has been reorganized, rest ruct ured, and in many areas
consolidat ed. Recent ref erences have been added and st ressed w hile many old
ref erences have been delet ed. A new chapt er on t he general principles of
localizat ion, w it h an int roduct ion t o t he localizat ion of processes aff ect ing t he
mot or syst em, sensory syst em, and gait , has been included.
This new edit ion of Localizat ion in Clinical Neurology is again direct ed and
dedicat ed t o “f ront line” clinicians w ho daily are conf ront ed w it h t he “Where is
it ?” of neurologic disorders. We hope t hat it may help t hem in t heir quest t o
diagnose t heir pat ient s w it h t he great est accuracy and t he least cost f rom
unnecessary t est ing.
We w ould like t o t hank our colleagues at t he Mayo Clinic in Jacksonville,
Scot t sdale, and Rochest er; t he hospit als aff iliat ed w it h t he New York Medical
College, t he Universit y of Navarra in Spain, and t he I ndiana Universit y School of
Medicine in I ndianapolis. O ur grat it ude goes in part icular t o t he f ollow ing
individuals: Doct ors Neil R. Miller, Andrew G . Lee, Frank A. Rubino, Jonat han D.
Trobe, James J. Corbet t , James F. Toole, Mark L. Dyken and William E. DeMyer.
We w ould especially like t o t hank Anne M. Sydor and Kerry Barret t of Lippincot t
Williams & Wilkins f or t heir encouragement , eff ort s, and prof essionalism and
Lorie G avulic f or her art ist ic renderings. As alw ays, t he support and
encouragement of f amily and f riends has been appreciat ed.
Paul W. Brazis
Jose C. Masdeu
José Biller
> Fr ont of B ook > P r efac e to the Fir s t E dition
Preface to the First Edition
This book may seem t o be born out of t ime. I s t here st ill a role f or clinical
localizat ion in neurologic pract ice in t he CT era? Not uncommonly, medical
st udent s echo t he w idespread opinion t hat t he pract ice of neurology has been
reduced t o t rying t o guess w hat t he CT scan or magnet ic resonance imaging w ill
show. As clinical neurologist s, w e w ish t his w ere t rue! I nst ead of spending long
hours int erview ing and examining pat ient s, w e w ould put t hem t hrough t he marvel
machines and speedily obt ain all t he diagnost ic inf ormat ion needed f or t heir
t reat ment . Unf ort unat ely, t he machines are not suff icient . The new t echniques
have meant a giant advance in our diagnost ic armament arium, but by no means
have t hey lessened t he need f or accurat e clinical diagnost ic evaluat ion. Brain
t umors and ot her lesions t hat dist ort t he anat omy of t he nervous syst em or
neighboring t issues can now be localized w it h much great er precision t han in t he
past . How ever, such lesions may go undet ect ed on imaging procedures unless
t hose procedures f ocus on t he region responsible f or t he pat ient 's sympt oms.
Furt hermore, neuroimaging may disclose anat omic anomalies not germane t o t he
pat ient 's present ing problem and of t en of no clinical import . These may be
pursued relent lessly unless a t horough underst anding of t he clinical pict ure
places t hem in proper perspect ive.
Nonet heless, CT has had an enormous impact on our underst anding of t he
clinical expression of diff erent brain lesions. Properly used, t he anat omic
inf ormat ion provided by CT has clarif ied a number of issues regarding
localizat ion, part icularly t he clinical expressions of acut e lesions and t heir
evolut ion over t ime and t he manif est at ion of space-occupying lesions such as
hydrocephalus and brain t umors. Many of t he ref erences in t his book ref lect t he
cont ribut ions of t he new er neuro-imaging t echniques t o t he f ield of clinical
localizat ion. The advances in t his f ield over t he past f ew years have been
remarkable. The present volume result ed f rom our int erest in document ing t he
new and emphasizing t he old in clinical neurologic localizat ion, at a t ime w hen
t his art cont inues t o play a cent ral role in t he evaluat ion of pat ient s w it h
neurologic disease. A number of w orks in recent years have dealt w it h t he
manif est at ions of disease in diff erent part s of t he nervous syst em. Books on t he
peripheral nervous syst em and t he cerebral hemispheres are not lacking, but
t here is a real deart h of t ext s providing a comprehensive discussion of
localizat ion in clinical neurology. Because many excellent account s are available
on ancillary diagnost ic means used in t he w ork-up of pat ient s w it h neurologic
disease, w e have f ocused on anat omic diagnosis as inf erred f rom t he pat ient 's
hist ory and physical f indings.
This book w as w rit t en w it h t he clinician in mind. Manif est at ions of neurologic
disease t hat are helpf ul f or localizat ion have been emphasized rat her t han t he
myriad “ref lexes” w it h high-sounding eponyms t hat have accumulat ed t hroughout
t he years in t he lit erat ure of neurology. We hope t hat not only t he physician in
t raining or pract ice, but also ot her healt h care prof essionals w ho deal w it h
neurologically impaired pat ient s w ill f ind helpf ul inf ormat ion in t he present
volume.
We t hank Drs. Frank A. Rubino and Sudhansu Chokrovert y, w ho f irst t aught us
t he import ance of neuroanat omic localizat ion, and Dr. Robert Tent ler, t hrough
w hom w e discovered t hat clinical neurology could be f un. We t hank also Drs.
Herman D. Barest , Herman Buschke, Richard Mayeux, I sabelle Rapin, Naemi
St ilman, Leon J. Thal, James F. Toole, and Daniel Wagner f or t heir assist ance in
review ing some of t he chapt ers, and f or t heir encouragement . For t heir support ,
w e are indebt ed t o t he Neurology Resident st aff s of Loyola Universit y Medical
Cent er and t he Albert Einst ein College of Medicine. Finally, w e express
appreciat ion t o Mrs. Helen Hlinka f or her secret arial help.
P. W. B.
J. C. M.
J. B.
> Table of C ontents > C hapter 1 - Gener al P r inc iples of Neur ologic Loc aliz ation
Chapter 1
General Principles of Neurologic Localization
Introduction
Fit t ingly, a book on localizat ion in clinical neurology should begin w it h a chapt er
explaining w hat t he t erm l ocal i zati on means. Localizat ion derives f rom t he Lat in
t erm l ocus or sit e. Localizat ion is t he diagnost ic exercise of det ermining f rom t he
signs (most of t en) or sympt oms of t he pat ient w hat sit e of t he nervous syst em
has been aff ect ed by a disease process. I mport ant injury t o t he nervous syst em
result s in abnormal f unct ion, be it behavioral, mot or, or sensory. Charact erist ics
of t he dysf unct ion of t en pave t he w ay f or a t opographic (f rom t he G reek t erm
topos or place) diagnosis. Localizat ion and t opographic diagnosis ref er t o t he
same t hing: t he det erminat ion of w here in t he nervous syst em t he damage has
occurred.
Even in t he age of sophist icat ed neurophysiology, neuroimaging, and molecular
biology, t he clinical diagnosis should precede t he use of t hese ot her t echniques if
t heir f ull diagnost ic pot ent ial is t o be realized. Clinical localizat ion has part icular
relevance t o t he adequat e use of ancillary procedures. For inst ance, f alse-
posit ive f indings f rom “gunshot approach” neuroimaging can only be avoided by
caref ul localizat ion. As an example, congenit al brain cyst s, st rikingly visible on
imaging procedures, are of t en w rongly blamed f or a variet y of neurologic
disorders, w hile t he act ual disease remains overlooked and unt reat ed. The
t hought f ul use of ancillary procedures in neurology, guided by clinical
localizat ion, minimizes discomf ort f or pat ient s and t he w ast e of resources.
A Brief History of Localization: Aphasia as an Example

The hist ory of localizat ion is t he hist ory of early neurology, concerned w it h
t opographic diagnosis t hat w ould event ually lead t o t herapy. I n f ew areas of
neurology w as t he development of localizat ion as int erest ing and so much at t he
cent er of f amous cont roversies as it w as in t he case of aphasia. I n f act , t he
oldest know n document on neurologic localizat ion concerns aphasia. I t w as
recorded in an Egypt ian papyrus f rom t he Age of t he Pyramids (about 3000–
2500 BC), w here an Egypt ian surgeon described t he behavior of an aphasic
individual:
I f t hou examinest a man having a w ound in his t emple,
penet rat ing t o t he bone, (and) perf orat ing his t emporal bone;
…if t hou ask of him concerning his malady and he speak not
t o t hee; w hile copious t ears f all f rom bot h his eyes, so t hat
he t hrust s his hand of t en t o his f ace so t hat he may w ipe
bot h his eyes w it h t he back of his hand … Edw in Smit h
surgical papyrus, Case 20, 2800 BC[10] .
From t he t ime of Hippocrat es, in ancient G reece, it w as document ed t hat injury

t o t he lef t part of t he brain result ed in w eakness of t he right side of t he body.
How ever, paired organs in t he body w ere t hought t o have ident ical f unct ions. I n
t he mid-19t h cent ury, Paul Broca (1824–1880) revolut ionized t he t hen current
underst anding of t he f unct ional organizat ion of paired organs by describing
lat eralizat ion of language t o t he lef t hemisphere[5, 11] . He called aphemi a t he
disorder t hat w e now call Broca's aphasi a. I n his 1865 paper, he w rot e:
Now, t his f unct ion of t he int ellect ual order, w hich cont rols t he
dynamic element as w ell as t he mechanical element of
art iculat ion, seems t o be t he nearly const ant privilege of t he
lef t hemisphere convolut ions, since lesions t hat result in
aphemia are almost alw ays localized in t hat hemisphere …
That is t ant amount t o saying t hat
P. 2
w e are lef t -brained w it h regard t o language. Just as w e
cont rol movement s in w rit ing, draw ing, embroidering, et c,
w it h t he lef t hemisphere, so w e speak w it h t he lef t
hemisphere.
Broca def ined t he inf erior f ront al gyrus as t he area t hat , w hen injured, w ould
lead t o aphemia [11] . He also not ed t he variat ion in t he expression of diverse
lesions in t he inf erior f ront al gyrus, charact erist ic of t he plast icit y f ound in
cort ical organizat ion:
During t he course of our st udy of brains of pat ient s w it h

aphemia, many t imes bef ore, w e had det ermined t hat t he
lesion of t he t hird lef t f ront al convolut ion w as not alw ays in
direct relat ion t o t he int ensit y and t he impairment of
language. For example, w e had observed t hat speech w as
complet ely w iped out as a result of a lesion w it h t he size of 8
t o 10 mm, w hereas, in ot her cases, lesions t hat w ere t enf old
more ext ensive had only part ly impaired t he capacit y f or
art iculat e speech.
I n t he f ew years af t er Broca's remarkable st at ement s, know ledge about t he

localizat ion of t he language cent ers in t he brain grew rapidly. Already in 1874,
Carl Wernicke (1848–1905) w rot e:
The w hole area of convolut ion encircling t he Sylvian f issure,

in associat ion w it h t he cort ex of t he insula, serves as a
speech cent er. The f irst f ront al gyrus, being mot or, is t he
cent er f or represent at ion of movement , and t he f irst t emporal
gyrus, being sensory, is t he cent er f or w ord images … The
f irst t emporal gyrus should be considered as t he cent ral end
of t he audit ory nerve, and t he f irst f ront al gyrus (including
Broca's area) as t he cent ral end of t he nerves t o t he speech
muscles … Aphasia can result f rom any int errupt ion of t his
pat h … The clinical pict ure w ill depend upon t he segment of
t he pat h involved …[ 62, 63] .
FI G URE 1-1 Wernicke's diagram of t he language areas. I n t he original, t he

label on t he superior t emporal gyrus w as simply a, but f rom t he cont ext , it
should have been a 1 . Wernicke's explanat ion of t his f igure is as f ollow s:
Let F be t he f ront al, O t he occipit al, and T t he t emporal end of a
schemat ically draw n brain. C is t he cent ral f issure; around t he Sylvian f issure
(S) ext ends t he f irst primit ive convolut ion. Wit hin t his convolut ion, ai is t he
cent ral end of t he acoust ic nerve, a it s sit e of ent ry int o t he medulla
oblongat a; b designat es t he represent at ion of movement s governing sound
product ion, and is connect ed w it h t he preceding t hrough t he associat ion
f ibers ai b running in t he cort ex of t he insula. From b t he eff erent pat hw ays
of t he sound-producing mot or nerves run t o t he oblongat a and exit t here …
(From Wernicke C, Der aphasi sche symptomencompl ex; ei ne
psychol ogi sche studi e auf anatomi scher basi s, Breslau: Max Cohn &
Weigert , 1874[ 62] . )
Know ledge of t he cort ical organizat ion f or language had been derived f rom
caref ul clinicopat hologic correlat ion[62] . Af t er describing a 73-year-old w oman
w it h t he sudden onset of conf used speech, Wernicke goes on t o describe t he
pat hologic f indings:
The branch of t he art ery of t he lef t Sylvian f issure, running

dow n int o t he inf erior sulcus of
P. 3
Burdach, w as occluded by a t hrombus t ight ly adherent t o t he
w all. The ent ire f irst t emporal gyrus, including it s junct ion
w it h t he second t emporal gyrus and t he origin of t he lat t er
f rom Bischof 's inf erior pariet al lobule w ere convert ed int o a
yellow ish-w hit e brei[62, 63] .
Wernicke's diagram of t he language areas is illust rat ed in Figure 1-1.

Current t echniques, like f unct ional brain mapping, promise t o clarif y f urt her t he
localizat ion of mechanisms underlying neurologic f unct ion. A quot at ion f ollow s
t hat exemplif ies how f unct ional neuroimaging and language-relat ed brain
pot ent ials are ref ining our underst anding of t he localizat ion of language
mechanisms:
The brain lesion–behavior approach has been complement ed

by neuroimaging st udies, such as PET and f unct ional MRI ,
w hich provide f urt her evidence t hat t he superior t emporal
gyrus and t he supramarginal gyrus support lexical processes
during audit ory language comprehension. These t ypes of
st udies have led t o a more det ailed f unct ional descript ion of
t he f ront al cort ices. I t appears t hat t he Brodmann areas (BA)
45/ 47/ 46 are involved in semant ic memory, w hereas BA 44 is
act ive during phonologically sequencing as w ell as during
grammat ical processing. …[ O ur result s w it h language-relat ed
brain pot ent ials] suggest t hat t he lef t f ront al cort ex might
support early parsing processes, and t hat specif ic regions of
t he basal ganglia, in cont rast , may not be crucial f or early
parsing processes during sent ence comprehension[21] .
Clinical Diagnosis and Lesion Localization

Clinical diagnosis in neurology requires several st eps:
1. Recognit ion of impaired f unct ion

2. I dent if icat ion of w hat sit e of t he nervous syst em has been aff ect ed, t hat is,
localizat ion
3. Def init ion of t he most likely et iology, of t en result ing in a diff erent ial
diagnost ic list
4. Use of ancillary procedures t o det ermine w hich of t he diff erent possible
et iologies is present in t he given pat ient
Each of t hese st eps is import ant . The f irst one, recognit ion of impaired f unct ion,
depends on a good hist ory and neurologic examinat ion. O nly by st oring t he range
of normal neurologic f unct ions in t heir mind can physicians recognize an
abnormal neurologic f unct ion. I nexperience or carelessness in examining a
pat ient of t en result s in overlooking a neurologic def icit and t heref ore missing a
diagnosis. For inst ance, mild chorea may appear t o t he inexperienced as normal
f idget iness. The slow eye movement s of a pont ocerebellar disorder may pass
complet ely unrecognized by someone w ho looks only f or a f ull excursion of t he
eyes.
Abnormal neurologic f indings come in t he f orm of abnormal behavior, impaired
post ure or gait , diff icult y w it h movement s of t he f ace or ext remit ies, and, f inally,
sensory dist urbances, including pain. Pain exemplif ies w ell several of t he
diff icult ies physicians f ace w hen conf ront ing possible neurologic dysf unct ion.
1. First , is t he dysf unct ion real? I s t he pain really t here or is t he pat ient t rying
t o deceive? We have w it nessed t he plight of a paraplegic pat ient w ho had
been repeat edly asked by healt h care personnel t o st op pret ending not t o be
able t o move his legs. They had misint erpret ed t he t riple f lexion response
w it nessed w hen t hey pulled t he sheet s off t he pat ient 's legs as evidence of
volit ional movement . Movement disorders, like t he dyst onias, w ere f requent ly
considered psychogenic in t he past and have gradually emerged f rom t his
realm int o a phase of general recognit ion of t heir “organicit y. ” Unless
accompanied by clear psychiat ric manif est at ions, neurologic sympt oms or
signs should be t aken at f ace value.
2. Second, t o w hat ext ent is t he dysf unct ion pat hologic, t hat is, indicat ive of
injury serious enough t o w arrant a f ormal diagnost ic w orkup? Many aches
and pains do not ref lect serious disease. Sending everyone w it h a “lit t le
pain” t o a physician w ould hopelessly clog up t he healt h care syst em.
I nt erest ingly, t he child learns f rom f alls and ot her minor injuries w hat t o
expect as “normal pain, ” and w hen a person seeks medical at t ent ion f or any
sympt om, t he likelihood is t hat t he problem is serious enough t o w arrant at
least a t hought f ul physical examinat ion.
3. Third, is t he dysf unct ion neurologic in origin? I s t he pain due t o injury of t he
aff ect ed body part or neurologic dysf unct ion? I s t he dysf unct ion a
manif est at ion of a disease of t he nervous syst em rat her t han of t he organ
mediat ing t he f unct ion? I s t he pat ient unable t o w alk because of “art hrit is” of
t he legs or because t he mot or syst em is aff ect ed? All t hese quest ions f ind
an answ er w hen t he physician recognizes pat t erns t hat belie neurologic
impairment , f or inst ance, in t he case of pain, a charact erist ic radicular
nat ure and dist ribut ion. I n ot her cases, t he neurologic examinat ion may
reveal ot her manif est at ions of unquest ionable neurologic dysf unct ion. A
pat ient w it h pain in
t he hand may also have at rophy of t he muscles in t he t henar eminence and a

Tinel's sign—pain on percussion of t he median nerve at t he w rist . Know ledge
of localizat ion t ells us t hat t he pain derives f rom injury of t he median nerve
at t he point w here t he pain increases on percussion. What is needed t o
localize t he lesion, in t his case as in any ot her, is a good w orking know ledge
of neuroanat omy.
Neuroanat omy is a key t o localizat ion. I n t his book, a synopsis of t he anat omy of
each st ruct ure of t he nervous syst em precedes t he discussion on localizat ion of
lesions of t hat st ruct ure. Neuroanat omy has t w o broad aspect s: t he morphology
of t he st ruct ure and it s “f unct ional represent at ion. ” “Funct ional represent at ion”
ref ers t o t he f unct ion mediat ed by a given st ruct ure of t he nervous syst em.
Damage t o t he st ruct ure result s in dysf unct ion in t he realm mediat ed by t his
st ruct ure. For example, an injury t o t he oculomot or nerve result s in mydriasis in
t he eye supplied by t his nerve.
Neuroanat omy provides t he road map f or localizat ion. Localizing is ident if ying t he
sit e of injury on t he neuroanat omic map. As w it h any ot her map, w e need eit her
an address, w it h st reet name and number, or t he int ersect ion bet w een t w o w ell-
def ined st reet s or roads. I njury expresses it self t hrough neurologic dysf unct ion,
be it behavioral, mot or, or sensory. I f w e know w hat kind of dysf unct ion can
result f rom injury of t he diff erent part s of t he nervous syst em, w e w ill be able t o
ident if y t he source of t he injury. Some t ypes of dysf unct ion direct ly give us t he
address w e are looking f or. A combinat ion of rest ing t remor, bradykinesia, and
rigidit y t ells us t hat t he subst ant ia nigra of t he pat ient has been injured. At ot her
t imes, w e use t he approach of looking f or t he int ersect ion bet w een t w o st reet s.
From some signs w e deduce t hat a part icular pat hw ay must be aff ect ed. From
ot hers, w e inf er t hat a second pat hw ay is aff ect ed as w ell. The injury must be in
t he place w here t hese pat hw ays meet . For inst ance, by t he presence of lef t -
sided hemiparesis w e inf er t hat t he cort icospinal t ract has been aff ect ed. But t he
cort icospinal t ract can be aff ect ed at t he level of t he spinal cord, brainst em, or
cerebral hemispheres. To precisely ident if y t he locat ion of damage w e need t o
use ot her clues. I f , in addit ion t o t he lef t -sided hemiparesis, w e f ind a right t hird
nerve palsy, w e are w ell on our w ay t o localizing t he lesion. This w ell-know n
syndrome, named af t er Weber, t ypif ies a general principle of localizat ion: t he
lesion is w here t he t w o aff ect ed pat hw ays cross. I f t he pat ient only had a t hird
nerve palsy, t he lesion could be anyw here bet w een t he f ascicle of t he nerve (in
t he brainst em) and t he superior orbit al f oramen (in t he orbit ). The addit ion of a
cont ralat eral hemiparesis precisely def ines t hat t he lesion aff ect s t he crus
cerebri in t he same side of t he t hird nerve palsy. This is w here t he cort icospinal
t ract and t he f ibers of t he t hird nerve meet . Neuroanat omy provides t he roadmap
f or a correct assessment .
Localizat ion t ends t o be more precise w hen t he lesion aff ect s t he low er levels of
t he nervous syst em. When w e localize lesions of t he nervous syst em, it is helpf ul
t o t hink about t he major syndromes t hat supervene w it h lesions at diff erent
f unct ional and anat omic levels, f rom t he muscle t o t he cort ex. At t he simplest
level, injury t o a muscle impairs t he movement mediat ed by t hat muscle. O ne
level higher, w e f ind t hat injury t o a peripheral nerve causes w eakness of t he
muscles innervat ed by t hat nerve and sensory loss in it s cut aneous dist ribut ion.
Lesions in t he spinal cord below t he low cervical level cause w eakness of one or
bot h legs and sensory loss t hat of t en has a horizont al level in t he t runk. Lesions
in t he cervical cord or brainst em t ypically cause w eakness or sensory loss on
one or bot h sides of t he body, of t en more severe on one side, and f indings
charact erist ic of t he level aff ect ed. For inst ance, lesions of t he cervical cord
may cause radicular pain or w eakness aff ect ing t he arms or hands. Lesions of
t he low er pons give rise t o gaze palsies or peripheral f acial w eakness. The
localizat ion of lesions in t he cranial nerves (CNs) is f airly st raight f orw ard
because t hey may aff ect a peripheral nerve or a neuroanat omic st ruct ure t hat is
relat ively simple, such as t he visual pat hw ays. As w e ascend t he neuraxis, t he
localizat ion of lesions becomes less precise. Lesions in t he cerebellum may
cause at axia. Lesions in t he t halamus of t en, but not alw ays, cause sensory loss
and post ural disorders, or memory loss. Lesions in t he hemispheric w hit e mat t er
may give rise t o w eakness or visual f ield def ect s. Finally, lesions in t he cort ex
manif est t hemselves by an array of mot or, sensory, or behavioral f indings t hat
vary according t o t he area t hat has been injured.
Similarly, lesions of t he low er levels t end t o cause f indings t hat change lit t le over
t ime, w hereas lesions of t he higher levels may be very “inconsist ent ” in t he
course of an examinat ion. An ulnar nerve lesion may be responsible f or at rophy
of t he f irst dorsal int erosseous muscle. The at rophy diagnosed by t he examiner
w ill be consist ent . By cont rast , a pat ient w it h a Broca's aphasia may have a
great deal of diff icult y repeat ing some w ords, but not ot hers of apparent ly
similar
diff icult y. The examiner may be puzzled and not know w hat t o document : can t he
pat ient repeat or can she not ? I n t his case, w hat should be not ed is not w het her
t he pat ient can do somet hing, but w het her she does it consist ent ly in a normal
w ay. Any diff icult y repeat ing a sent ence on t he part of a nat ive speaker of a
language should be considered as abnormal. Higher neurologic f unct ion should
be sampled enough t o avoid missing a def icit t hat t he more complex neural
net w orks of higher levels can easily mask.
For t he anat omic localizat ion of lesions, t he neurologic examinat ion is much more
import ant t han t he hist ory. I t must be not ed t hat w hen w e speak here about
“examinat ion, ” w e include t he sensory f indings report ed by t he pat ient during t he
examinat ion. A complaint of pain or of numbness is usually as “object ive” as a
w rist drop. By t racking back t he pat hw ays t hat mediat e t he f unct ions t hat w e
f ind are impaired in t he neurologic examinat ion, w e can generally localize t he
sit e of t he lesion, even w it hout a hist ory. The hist ory, t hat is, t he t emporal
evolut ion of t he def icit s w it nessed in t he neurologic examinat ion, is import ant in
def ining t he precise et iology. For inst ance, a lef t -sided hemiparesis is det ect ed
in t he neurologic examinat ion. I f it occurred in a mat t er of minut es,
cerebrovascular disease or epilepsy is most likely. I f it evolved over a f ew days,
w e should t hink about an inf ect ion or demyelinat ing disease. I f it developed
insidiously, in a mat t er of mont hs, a t umor or a degenerat ive process is more
likely. I n all of t hese cases, t he localizat ion is derived f rom t he f indings of t he
examinat ion: w e det ect a lef t -sided hemiparesis. I f w e also f ind a right t hird
nerve palsy and det ermine t hat it has appeared at t he same t ime as t he
hemiparesis, w e w ill emphasize t he need f or a caref ul look at t he midbrain w hen
w e obt ain a magnet ic resonance imaging (MRI ). I n t his sense, t he hist ory is also
import ant f or localizat ion: w e may w it ness in t he examinat ion t he end result of
mult iple lesions t hat aff ect ed t he nervous syst em over t ime. I n t he previous
example, if t he t hird nerve palsy occurred w hen t he pat ient w as 10 years old and
t he hemiparesis appeared w hen he w as in his sixt ies, t he lesion responsible f or
t he hemiparesis w ould probably not be in t he midbrain.
Finally, t here is t he issue of discret e lesions versus syst em lesions. Much of t he
w ork on localizat ion has been done on t he basis of discret e lesions, such as an
inf arct aff ect ing all t he st ruct ures in t he right side of t he pons. Some t ypes of
pat hologies t end t o cause t his t ype of lesion. Cerebrovascular disease is t he
most common, but demyelinat ing lesions, inf ect ions, t rauma, and t umors also
of t en behave like discret e, single, or mult iple lesions. O t her neurologic disorders
aff ect arrays of neurons, of t en responsible f or a f unct ional syst em. Parkinson's
disease is an example. Here, t he localizat ion t o t he subst ant ia nigra is simple.
The localizat ion of ot her degenerat ive disorders, such as t he spinocerebellar
degenerat ion of abet alipoprot einemia or vit amin E def iciency, is more
complicat ed[ 51] . Here, t he clinical syndrome seems t o point t o t he spinal cord,
but t he real damage is inf lict ed t o t he large neurons in t he sensory nuclei of t he
medulla, dorsal root ganglia, and Bet z cells. The puzzle is resolved w hen one
realizes t hat t he dest ruct ion of t he cort icospinal t ract logically f ollow s met abolic
injury t o t he neurons t hat give rise t o it . The larger neurons, w it h t he longest
axons reaching t he lumbar segment s, are aff ect ed f irst . The neuron may not die,
but , incapable of keeping an act ive met abolism, it begins t o ret ract it s axon
(dying-back phenomenon). Likew ise, t he lesion in t he dorsal columns of t he
spinal cord (and peripheral nerve) simply ref lect s t he damage inf lict ed t o t he
larger sensory neurons by t he lack of vit amin E. Theref ore, a precise know ledge
of t he f unct ional signif icance of t he diff erent st ruct ures of t he neuraxis f acilit at es
t he localizat ion of degenerat ive or syst em lesions as much as it helps w it h
discret e lesions.
Having review ed some general principles of localizat ion in t he nervous syst em,
w e w ill now review in more det ail t he principles of localizat ion in t he mot or and
sensory syst ems. Finally, w e w ill review t he localizat ion of gait disorders.
Localization of Lesions of The M otor System

Anatomy of the Motor System
The mot or neurons of t he vent ral horn of t he spinal cord and t he mot or nuclei in
t he brainst em, w hose axons synapse direct ly on st riat ed muscles, are t he “f inal
common pat hw ay” f or muscle cont rol. These large al pha (α) motor neurons
supply t he ext raf usal f ibers of t he skelet al muscles. Scat t ered among t he lα
mot or neurons are many small gamma (γ) motor neurons, w hich supply t he
int raf usal f ibers of t he muscle spindles. The mot or neuron, t oget her w it h t he
muscle f ibers it supplies, is called t he motor uni t. The junct ion bet w een t he
t erminal branches of t he axon and t he muscle f iber is called t he neuromuscul ar
juncti on[ 20, 45] . There is a somatotopi c organi zati on of t he cell columns of
ant erior horn cells in t he vent ral gray horn of t he spinal cord. Neurons t hat
supply t he axial muscles, including t he neck muscles, are
locat ed in vent romedially placed columns; neurons t hat supply proximal muscles
are sit uat ed in t he midregion; and neurons supplying t he musculat ure of t he
dist al aspect of t he limbs are locat ed in lat erally placed columns[20, 45] .
Mot or neuronal cell groups receive input f rom t he cont ralat eral mot or cort ex
(MC) t hrough t he descending corti cospi nal and corti cobul bar t ract s (Figs. 1-2A
and B). The cort icospinal t ract cont ains on each side approximat ely 1 million
f ibers of various sizes, but only 3% of all t he f ibers originat e f rom t he gi ant
pyrami dal cel l s of Betz f ound in layer V in t he primary MC. All cort icospinal
f ibers are excit at ory and appear t o use glut amat e as t heir neurot ransmit t er. The
neurons f rom w hich t he cort icospinal and cort icobulbar t ract s arise are know n as
upper motor neurons [ 2, 4, 20, 29, 61] . The corti cospi nal pathway, w hich
cont rols volunt ary, discret e, highly skilled movement s of t he dist al port ion of t he
limbs, arises f rom somat ot opically organized areas of t he primary MC, lat eral
premot or cort ex (PMC), and supplement ary mot or area (SMA). These f ibers
arise f rom bot h precent ral (60%) and post cent ral (40%) cort ical areas. The
cort icospinal neurons are f ound primarily in Brodmann's area 4 (40%), w hich
occupies t he post erior port ion of t he precentral gyrus (primary MC). The lat eral
PMC, on t he lat eral aspect of t he f ront al lobe, and t he SMA, on it s medial part ,
are locat ed in Brodmann's area 6 (20%). Cort icospinal axons also arise f rom
neurons in t he primary sensory cort ex in t he postcentral gyrus (Brodmann's
areas 3, 1, and 2), part icularly f rom area 3a, anteri or paracentral gyri ; superi or
pari etal l obul e (Brodmann's areas 5 and 7); and port ions of t he ci ngul ate gyrus
on t he medial surf ace of t he hemisphere. Fibers of t he cort icospinal syst em
descend in t he corona radiat a, t he post erior limb of t he int ernal capsule, t he
middle t hree-f if t hs of t he cerebral peduncle, t he basis pont is (w here t he t ract is
broken int o many bundles by t he t ransverse pont ocerebellar f ibers), and t he
medullary pyramids.
I n t he caudal end of t he medulla, nearly 75% t o 90% of t he cort icospinal f ibers in
t he pyramid cross t he vent ral midline (pyrami dal decussati on or Mi sti chel l i
crossi ng) bef ore gat hering on t he opposit e side of t he spinal cord as t he l ateral
corti cospi nal tract. I n t he post erior limb of t he int ernal capsule, t he cort icospinal
t ract is organized somat ot opically, w it h hand f ibers lat eral and slight ly ant erior t o
f oot f ibers[30] . The cort icospinal f ibers also f ollow a somat ot opic organizat ion in
t he pons. Fibers cont rolling t he proximal muscles are placed more dorsal t han
t hose cont rolling t he more dist al muscle groups. Because of t he vent ral locat ion
of t he pyramidal t ract in t he pons, a pure mot or hemiparesis of brainst em origin
is usually observed w it h pont ine lesions. Unilat eral mot or def icit s may
predominant ly involve t he upper or low er limb, but a diff erence in t he pont ine
lesion locat ion among t hese pat t erns of w eakness dist ribut ion is not
observed[ 39] . There is also a somat ot opic organizat ion of t he cort icospinal
f ibers w it hin t he medullary pyramids, w it h f ibers of t he low er ext remit ies placed
more lat erally and decussat ing more rost rally t han t hose of t he upper
ext remit ies[ 22] . The remaining f ibers t hat do not decussat e in t he medulla
descend in t he ipsilat eral vent ral f uniculus as t he ventral or anteri or
corti cospi nal tract ( Türck's bundl e). Most of t hese f ibers ult imat ely decussat e at
low er spinal cord levels as t hey f urt her descend in t he ant erior column of t he
spinal cord. Theref ore, only approximat ely 2% of t he descending cort icospinal
f ibers remain t ruly ipsilat eral, f orming t he bundl e of Barnes[ 2] . These ipsilat eral
descending project ions cont rol t he axial musculat ure of t he t runk and proximal
limbs.
The corti cobul bar f i bers, originat ing in t he low er t hird of t he cort ical mot or
f ields, especially t he MC and SMA, descend in t he genu of t he int ernal capsule,
t he medial part of t he cerebral peduncle, and t he basis pont is, w here t hey are
int ermixed w it h cort icospinal f ibers. The cort icobulbar pat hw ay has bilat eral input
t o t he nuclei of t he t rigeminal and hypoglossal CNs, as w ell as t he f acial nucleus
supplying t he upper f acial muscles. Tradit ional localizat ion concept s post ulat e
t hat vent ral brainst em lesions rost ral t o t he low er pons result in cont ralat eral
cent ral f acial paresis, w hereas lesions of t he low er dorsolat eral pons result in
ipsilat eral f acial paresis of t he peripheral t ype. How ever, an aberrant f iber
bundle branching off t he main pyramidal t ract at t he midbrain and upper pons,
along t he t egment um in a paralemniscal posit ion, has been described. Theref ore,
w hereas t he muscles of t he low er f ace receive predominant ly crossed
cort icobulbar input , t he muscles of t he upper f ace are represent ed in t he
ipsilat eral, as w ell as t he cont ralat eral, hemisphere, w it h t ranscranial magnet ic
st imulat ion (TMS) st udies show ing t hat t he amount of uncrossed pyramidal
project ions are no diff erent f rom t he muscles of t he upper t han t hose of t he
low er f ace[18, 56] . TMS st udies in pat ient s w it h and w it hout cent ral f acial
paresis due t o brainst em lesions have also show n t hat a supranuclear f acial
paresis may be cont ralat eral t o a lesion of t he cerebral peduncle, pont ine base,
aberrant bundle or vent ral medulla, or ipsilat eral t o a lat eral medullary
lesion[ 59] .
FI G URE 1-2A A simplif ied diagram of t he mot or syst em. A: Cort icospinal
t ract .
FI G URE 1-2B B: Cort icobulbar t ract .
The vent ral part of t he f acial nucleus, innervat ing t he low er t w o-t hirds of t he
f ace, has a predominant ly crossed supranuclear cont rol. This schema of
supranuclear f acial muscle cont rol holds t rue f or volunt ary f acial movement s.
Emot ional involunt ary movement s and volunt ary f acial movement s may be
clinically dissociat ed, and t heref ore, a separat e supranuclear pat hw ay f or t he
cont rol of involunt ary movement s probably exist s. A prevailing view is t hat t he
SMA and/ or cingulat e mot or areas are crit ical f or emot ional f acial
innervat ion[ 32] . Fibers mediat ing emot ional f acial movement s do not descend in
t he int ernal capsule in t heir course t o t he f acial mot or nuclei. The right cerebral
hemisphere is also involved in supranuclear emot ional f acial movement cont rol
and is “dominant ” f or t he expression of f acial emot ion[8] . Furt hermore, some of
t he f acial cort icobulbar f ibers seem t o descend ipsilat erally bef ore making a loop
as low as t he medulla and decussat ing and ascending t o t he cont ralat eral f acial
nucleus (locat ed dorsolat erally in t he caudal pons) t hat innervat es t he perioral
f acial musculat ure[15, 57] . This anat omic underst anding explains t he emot ional
f acial paresis of pont ine origin result ing f rom t he involvement of t he dorsal
lat eral pont ine area[31] .
Wit hin t he MC, cort icospinal neurons are somat ot opically organized in pat t erns
t hat ref lect t heir f unct ional import ance (motor homuncul us). The size of t he
cort ical represent at ion in t he mot or homunculus varies w it h t he f unct ional
import ance of t he part represent ed; t heref ore, t he lips, jaw, t humb, and index
f inger have a large represent at ion, w hereas t he f orehead, t runk, and proximal
port ions of t he limbs have a small one. As an example, isolat ed hand w eakness
of cort ical origin may present w it h loss of t humb and f inger movement s and
impaired hand f lexion and ext ension or w it h part ial involvement of a f ew digit s
(pseudoradicular pat t ern). This cort ical mot or hand area has been localized in
t he middle t o low er port ion of t he ant erior w all of t he cent ral sulcus (Brodmann's
area 4), adjacent t o t he primary sensory cort ex of t he hand (Brodmann's areas
3a and 3b)[ 55] . Neurons in t he medial aspect of t he MC and t he ant erior
paracent ral gyrus inf luence mot or neurons innervat ing t he muscles of t he f oot ,
leg, and t high. Neurons in t he medial t w o-t hirds of t he precent ral gyrus inf luence
mot or neurons innervat ing t he upper ext remit y and t runk. Neurons in t he
vent rolat eral part of t he precent ral gyrus cont ribut e t o t he cort icobulbar t ract
and project t o mot or nuclei of t he t rigeminal (CN V), f acial (CN VI I ),
glossopharyngeal (CN I X), vagus (CN X), accessory (CN XI ), and hypoglossal
(CN XI I ) nerves t o inf luence t he cranio-f acial-oral musculat ure[4, 29] . As an
example, each hypoglossal nucleus receives impulses f rom bot h sides of t he
cerebral cort ex, except f or t he genioglossus muscle t hat has probably crossed
unilat eral innervat ion. Theref ore, a lingual paresis may occur w it h lesions at
diff erent anat omic levels including t he medulla, hypoglossal f oramen, cervical
(neck) region, ant erior operculum, and post erior limb of t he int ernal capsule[24] .
Sensory cort ical pat hw ays (e. g. , t halamocort ical connect ions), cort icof ugal
project ions t o ret iculospinal and vest ibulospinal t ract s, direct cort icospinal
project ions t o t he spinal cord, and project ions t o t he basal ganglia and
cerebellum have an act ive role in t he planning and execut ion of movement s. The
cerebellum and basal ganglia are crit ically import ant f or mot or f unct ion [2, 4,
61] . The cerebel l um has a major role in t he coordinat ion of movement s and
cont rol of equilibrium and muscle t one. The cerebellum cont rols t he ipsilat eral
limbs t hrough connect ions w it h t he spinal cord, brainst em, and cont ralat eral MC
t hrough t he t halamus. A cort icof ugal pat hw ay of major clinical import ance is t he
cort icopont ine pat hw ay, w hich arises primarily f rom t he precent ral and
post cent ral gyri, w it h subst ant ial cont ribut ions f rom t he PMC, SMA, and
post erior pariet al cort ices, and f ew f rom t he pref ront al and t emporal cort ices.
These f ibers descend in t he ant erior limb of t he int ernal capsule and t he medial
f if t h of t he cerebral peduncle bef ore reaching t he basis pont is, w here t hey
project t o pont ine nuclei. Second-order neurons f rom pont ine nuclei cross t o t he
cont ralat eral basis pont is and give rise t o t he pont ocerebellar pat hw ay.
The basal gangl i a play a major role in t he cont rol of post ure and movement and
part icipat e in mot or planning t hrough reciprocal connect ions w it h ipsilat eral MC.
The cort icost riat e pat hw ay includes direct and indirect project ions f rom t he
cerebral cort ex t o t he st riat um. Cort icost riat e project ions arise mainly f rom
mot or–sensory cort ex (Brodmann's areas 4 and 3, 1, and 2), PMC (Brodmann's
area 6), and f ront al eye f ields (Brodmann's area 8). Direct cort icost riat e
project ions reach t he st riat um t hrough t he int ernal and ext ernal capsules and t he
subcallosal f asciculus. The indirect pat hw ays include t he cort ico-t halamo-st riat e
pat hw ay, collat erals of t he cort icoolivary pat hw ay, and collat erals of t he
cort icopont ine pat hw ay. All part s of t he cerebral cort ex give rise t o eff erent
f ibers t o t he caudat e and put amen. Cort ical associat ion areas project mainly t o
t he caudat e nucleus, w hereas sensorimot or areas project pref erent ially t o t he
put amen. These cort icost riat e project ions mainly t erminat e ipsilat erally in a
t opographic pat t ern
(e. g. , t he f ront al cort ex project s f ibers t o t he vent ral head of t he caudat e and
rost ral put amen). The cort ex also sends f ibers t o t he subst ant ia nigra,
subt halamic nucleus, and claust rum.
Anot her cort icof ugal t ract of major clinical import ance is t he corti cothal ami c
pathway. This pat hw ay arises f rom cort ical areas receiving t halamic project ions
and, t heref ore, serves as a f eedback mechanism f rom t he cort ex t o t he t halamic
nuclei. Except f or t he ret icular nucleus of t he t halamus, examples of such
reciprocal connect ions include t he ant erior nucleus and t he post erior cingulat e
cort ex, t he vent ral lat eral nucleus and t he MC, t he vent ral ant erior nucleus and
t he SMA, t he vent ral post erior nucleus and t he primary sensory cort ex, t he
lat eral geniculat e body and t he primary visual cort ex, t he medial geniculat e body
and t he primary audit ory cort ex, and t he dorsomedial nucleus and t he pref ront al
cort ex. Cort icot halamic f ibers descend in various part s of t he int ernal capsule
and ent er t he t halamus in a bundle know n as t he thal ami c radi ati on.
Addit ional cort icof ugal t ract s include t he cort icoret icular pat hw ay, w hich arises
f rom one cerebral hemisphere, descends in t he genu of t he int ernal capsule, and
project s t o bot h sides of t he brainst em ret icular f ormat ion, and t he highly
int egrat ed cort icohypot halamic t ract , w hich arises f rom t he pref ront al cort ex,
cingulat e gyrus, amygdala, olf act ory cort ex, hippocampus, and sept al area.
Cort icof ugal areas f rom t he f ront al eye f ields (Brodmann's area 8) and t he
middle f ront al gyrus (Brodmann's area 46) project t o t he superior colliculus and
cent ers in t he brainst em ret icular f ormat ion t hat inf luence t he mot or nuclei of t he
oculomot or (CN I I I ), t rochlear (CN I V), and abducens (CN VI ) nerves[6] .
The i nternal capsul e, a compact lamina of w hit e mat t er, cont ains aff erent and
eff erent nerve f ibers passing t o and f rom t he brainst em t o t he cerebral
hemispheres, t hat is, cont inuous rost rally w it h t he corona radiat a and caudally
w it h t he cerebral peduncles. Locat ed medially bet w een t he caudat e nucleus and
t he t halamus, and lat erally in t he lent icular nucleus (globus pallidus and
put amen), in a horizont al (Flechsig) sect ion, t he int ernal capsule is somew hat
curved w it h it s convexit y inw ard. The prominence of t he curve (genu) project s
bet w een t he caudat e nucleus and t he t halamus. The port ion in f ront of t he genu
is called t he anteri or l i mb, w hich measures approximat ely 2 cm in lengt h and
separat es t he lent icular nucleus f rom t he caudat e nucleus (lent iculocaudat e
segment of t he int ernal capsule). The port ion behind t he genu is t he posteri or
l i mb, w hich measures 3 t o 4 cm in lengt h and separat es t he lent icular nucleus
f rom t he t halamus (lent iculot halamic segment ). The int ernal capsule ext ends
f urt her t o include subl enti cul ar and retrol enti cul ar segment s.
The ant erior limb of t he int ernal capsule cont ains f ront opont ine f ibers, and
t halamocort ical and cort icot halamic f ibers (reciprocally connect ing t he f ront al
lobe t o t he t halamus), as w ell as caudat oput aminal f ibers. Cort icobulbar f ibers,
and perhaps mot or cort icopont ine f ibers, occupy t he genu of t he int ernal
capsule. This f iber arrangement explains t he f acial and lingual hemiparesis w it h
mild limb involvement observed in t he capsular genu syndrome[7] . I n t he caudal
half of t he post erior limb of t he int ernal capsule, t he cort icospinal bundle is
somat ot opically organized in such a w ay t hat t he f ibers t o t he upper ext remit y
are locat ed more ant eriorly (i. e. , shoulder, elbow, w rist , and f ingers), f ollow ed
by f ibers t o t he t runk and t hen by t he f ibers t o t he low er ext remit y (i. e. , hip,
knee, ankle, t oes), bladder, and rect um. As t he cort icospinal t ract descends
t hrough t he int ernal capsule, it s f ibers int ermix w it h ot her f iber syst ems including
cort icorubral, cort icoret icular, and cort icopont ine f ibers. Cort icorubral,
cort icot halamic, and t halamocort ical f ibers (carrying sensory t ract s f rom t he
t halamus t o t he pariet al lobes) are also locat ed dorsal t o t he cort icospinal
f ibers, in t he post erior limb of t he int ernal capsule. Finally, t he sublent icular
segment of t he int ernal capsule cont ains t he audit ory and visual radiat ions, w hile
t he ret rolent icular segment cont ains t he visual radiat ions of G rat iolet 's radiat ing
f ibers and cort icot ect al, cort iconigral, and cort icot egment al f ibers. The ant erior
limb of t he int ernal capsule receives it s vascular supply f rom t he art ery of
Heubner, a branch of t he ant erior cerebral art ery; t he genu and t he middle and
inf erior part of t he post erior limb receive t heir blood supply f rom t he ant erior
choroidal art ery; w hile t he superior aspect of t he ant erior and post erior limb of
t he int ernal capsule receive t heir blood supply f rom t he lent iculost riat es,
branches of t he middle cerebral art ery.
Motor Signs and Symptoms and Their Localization

Pat ient s w it h mot or def icit s may present w it h pl egi a or paresi s. Plegia denot es
complet e paralysis; paresis denot es a lesser degree of w eakness. How ever, in
daily clinical parlance, t he w ord paralysis is of t en used f or bot h complet e and
part ial loss of mot or f unct ion. Muscle st rengt h t est ing is graded according t o t he
Medical Research Council's scale f or muscle pow er (Table 1-1), w hich has a
good int erobserver reliabilit y. Normal grading means t hat t he muscle is capable
of holding
t he t est posit ion against st rong pressure. G rade 4 is of t en subdivided int o 4–, 4,
and 4+ t o indicat e movement against slight , moderat e, and st rong resist ance,
respect ively. Common pat t erns of w eakness include monopl egi a (single limb
w eakness), hemi pl egi a (loss of mot or f unct ion dow n one side of t he body),
parapl egi a (bilat eral loss of low er limb mot or f unct ion), quadri pl egi a or
tetrapl egi a (loss of mot or f unct ion in all f our ext remit ies), brachi al di pl egi a (loss
of mot or f unct ion of bot h upper ext remit ies), or f aci al di pl egi a (loss of mot or
f unct ion of bot h halves of t he f ace). O t her pat t erns seen in children include
doubl e hemi pl egi a, charact erized by severe spast icit y in all f our ext remit ies,
w hich is more severe in t he arms t han in t he legs, and cerebral di pl egi a, w here
t he spast ic paralysis usually aff ect s all f our ext remit ies and involves t he legs
more t han t he arms.
TABLE 1-1 M edical Research Council's Scale for

Assessment of M uscle Pow er
Scale Description
0 No muscle contraction visible
1 Flicker or trace of contraction, but no movement
Active joint movement when effect of gravity is

2
eliminated
3 Active movement against gravity
Active movement against gravity and

4
resistance, but weaker than normal
5 Normal power
When examining pat ient s aff lict ed w it h any of t hese pat t erns of w eakness, one
should have t hree f undament al quest ions in mind: (a) w here is t he lesion? (b) I s
t he lesion f ocal, mult if ocal, or diff use? and (c) What is t he likely underlying
cause? The f irst and second quest ions are answ ered by perf orming a f ocused
neurologic examinat ion; t he answ er t o t he last quest ion requires det ailed hist ory
and invest igat ions.
Lesions in t he descending mot or syst em can be locat ed in t he cerebral cort ex,
int ernal capsule, brainst em (cerebral peduncles, pons, medulla oblongat a), or
spinal cord. Cort ical lesions leading t o spast icit y involve t he primary mot or and
premot or cort ical areas. Alt hough t he upper mot or neuron t ype of paralysis is
of t en ref erred t o as pyrami dal syndrome, lesions account ing f or t his clinical
pict ure involve more t han t he pyramidal t ract , and t heref ore, t he usage of t his
t erm is t o be discouraged. Lesions of t he low er mot or neurons can be locat ed in
t he cells of t he vent ral gray column of t he spinal cord or brainst em or in t he
axons of t hese neurons.
The upper mot or neuron syndrome may f ollow head or spinal cord injury,
perinat al brain injuries, st roke, demyelinat ing diseases such as mult iple
sclerosis, or mot or neuron diseases such as amyot rophic lat eral sclerosis or
primary lat eral sclerosis. The clinical present at ion of t he upper mot or neuron
syndrome f ollow ing cort ical lesions is somew hat diff erent f rom t hat of spinal
cord lesions. Likew ise, t here may be subt le diff erences bet w een incomplet e and
complet e spinal cord lesions[52] . I n general, spast icit y is less severe w it h
cerebral lesions t han w it h spinal cord lesions. Damage t o t he upper motor
neurons result s in muscles t hat are init ially w eak and f laccid but event ually
become spast ic and exhibit hypert onia and hyperact ivit y of t he st ret ch ref lexes
(hyperref lexia). Muscle st ret ch ref lexes consist of a monosynapt ic arc w it h
large-diamet er aff erent (sensory) nerve f iber input f rom muscle spindle f ibers
and large-diamet er eff erent (mot or) nerve f iber out put f rom α mot or neuron
f ibers. Clonus, charact erized by a series of rhyt hmic cont ract ion and relaxat ion
of a group of muscles, is best seen at t he ankle. Spast icit y, a mot or component
of t he upper mot or neuron syndrome, is best charact erized by a velocit y-
dependent increase in muscle t one w it h exaggerat ed t endon jerks, result ing f rom
hyperexcit abilit y of t he st ret ch ref lex[35] . Spast icit y predominat es in ant igravit y
muscles (f lexors of t he upper ext remit ies and ext ensors of t he low er
ext remit ies). Evaluat ion of muscle t one show s variable degree of resist ance t o
passive movement s w it h changes in speed and direct ion of passive mot ion and a
cl asp-kni f e character; in ot her w ords, great er resist ance is f elt w it h f ast er
st ret ches. Weakness of t he muscles of t he upper ext remit y is most marked in t he
delt oid, t riceps, w rist ext ensors, and f inger ext ensors; t his predilect ion f or
involvement of t he ext ensors and supinat ors explains t he pronat ion and f lexion
t endencies of t he upper limb. Weakness of t he muscles of t he low er ext remit y is
most marked in hip f lexors, knee f lexors, f oot dorsif lexors, and f oot evert ors.
Diff erent anat omic subst rat es may underlie hyperref lexia and spast icit y;
likew ise, spast icit y must be clearly separat ed f rom f lexor spasms (see
subsequent t ext ). As an example, cort icospinal lesions in t he cerebral peduncle
do not result in spast icit y, and lesions conf ined t o t he medullary pyramid may
cause w eakness and hyperref lexia w it hout spast icit y[53] . The upper mot or
neuron syndrome
is associat ed w it h t he presence of pat hologic ref lexes and signs, such as t he

ext ensor plant ar ref lex or Babinski's sign, a disinhibit ed f lexion w it hdraw al ref lex,
charact erized by dorsif lexion (ext ension) of t he big t oe of t en accompanied by
abduct ion of t he ot her t oes. How ever, such response is t o be considered normal
unt il t he age of 1 year. Furt hermore, severe f lexor or less common ext ensor
muscle spasms may also occur in response t o a variet y of nocicept ive or
nonnocicept ive sensory st imuli, or may develop spont aneously. Flexor spasms,
resembling t he f lexor w it hdraw al ref lex, of t en consist of f lexion of t he hip, knee,
and ankle, w hereas ext ensor spasms of t en involve t he ext ensors of t he hip and
knee w it h plant ar f lexion and ankle inversion. Unlike cerebral lesions, spinal cord
lesions are of t en associat ed w it h marked f lexor spasms, except f or incomplet e
or high spinal cord lesions t hat usually have a dominant ext ensor t one. Severe
f lexor spasms may also be accompanied by bladder and, occasionally, f ecal
incont inence. O t her manif est at ions (negat ive f eat ures) seen w it h t he upper mot or
neuron syndrome include muscle w eakness, impaired dext erit y, and f at igabilit y.
I n addit ion, pat ient s w it h severe spast icit y may exhibit muscle def ormit ies,
cont ract ures, and associat ed react ions including synkinesias[9] .
Finally, t he superf icial ref lexes are absent on t he aff ect ed side. Wit h lesions
above t he pyramidal decussat ion, t he previously discussed signs are det ect ed on
t he opposit e side of t he body; w it h lesions occurring below t he pyramidal
decussat ion, t hese signs are observed ipsilat erally.
When t he l ower motor neurons or t heir axons are damaged, t he innervat ed
muscles w ill show some combinat ion of t he f ollow ing signs: w eakness or
paralysis of t he involved muscles, f laccidit y, hypot onia, diminished or absent
muscle st ret ch ref lexes (hyporef lexia or aref lexia), and event ually at rophy. Some
pat t erns of discret e muscle at rophy have localizing value, as is t he case of early
neuropat hic compromise, w it h involvement of t he f irst dorsal int erosseus of t he
hand and t he ext ensor digit orum brevis in t he f eet . Fasciculat ions, w hich are
visible t w it ches of small groups of muscle f ibers, may be present . No pat hologic
ref lexes are elicit ed.
The topographi c di agnosi s of a hemi pl egi a requires a st ruct ured approach t o
pat ient evaluat ion on t he basis of localizat ion and a basic underst anding of
applied neuroanat omy. When a pat ient present s w it h hemiplegia or hemiparesis,
it is import ant t o det ermine w het her t he low er half of t he f ace is involved w it h
relat ive sparing of upper f acial f unct ion. Then, one must det ermine w het her t he
hemiparesis is proport ionat e or disproport ionat e (e. g. , similar degree of muscle
w eakness of t he upper and low er limbs). A caref ul search f or neighboring signs
or sympt oms, such as ipsilat eral hemisensory def icit , aphasia, homonymous
hemianopia, anosognosia, or hist ory of part ial mot or or somat osensory seizures
could great ly assist w it h localizat ion. Facial w eakness can be of t he upper or t he
low er mot or neuron t ype. I f t here is f acial w eakness of t he upper mot or neuron
t ype (involvement of t he low er half of t he f ace w it h relat ive sparing of muscles of
t he upper part of t he f ace) on t he same side of t he hemiplegia, t he lesion is
generally localizable above t he upper pons; likely sit es are t he MC, corona
radiat a, or int ernal capsule. How ever, a lesion on t he cerebral peduncles and
upper pons can also cause a hemiplegia or hemiparesis w it h an associat ed upper
mot or neuron t ype of f acial paresis. I f t he hemiparesis is disproport ionat e, t hat
is, t he f ace and arm are charact erist ically more severely aff ect ed t han t he leg
(e. g. , f aciobrachial predominance), t he lesion is of t en cort icosubcort ical and
lat erally placed on t he cont ralat eral hemisphere. I f t he leg is more severely
aff ect ed t han t he arm and f ace (e. g. , crural predominance of t he hemiparesis),
t he lesion most likely involves t he cont ralat eral paracent ral region. I n cases of
int ernal capsule lesions, t he hemiplegia is of t en proport ionat e, w it h equal
involvement of t he f ace and upper and low er limbs. I nt ernal capsular lesions
usually cause a pure mot or hemiplegia; ot her locat ions of lesions causing a pure
mot or hemiplegia include t he basis pont is, t he cerebral peduncle, and t he
medullary pyramid. Capsular lesions may rarely cause a f aciobrachial or crural
predominant t ype of hemiplegia. I nf arct ions in t he t errit ory of t he ant erior
choroidal art ery result in hemiparesis because of t he involvement of t he
pyramidal t ract in t he post erior limb of t he int ernal capsule, hemisensory loss
due t o involvement of t he superior t halamic radiat ions sit uat ed in t he
t halamogeniculat e segment of t he post erior limb of t he int ernal capsule, and
hemianopia secondary t o t he involvement of t he opt ic t ract , t he lat eral geniculat e
body, t he opt ic radiat ions, or combinat ion of t hese (see Chapt er 21). I n cases of
alt ernat ing hemiplegia, t here are “crossed” signs, w it h CN involvement ipsilat eral
t o t he lesion and hemiparesis or hemiplegia cont ralat eral t o t he lesion. This t ype
of “crossed” syndrome point s t o a brainst em lesion (see Chapt er 15). For
example, a lesion at t he level of t he cerebral peduncle may damage t he
pyramidal f ibers and t he f ascicle of CN I I I , causing an ipsilat eral oculomot or
paresis w it h pupillary involvement and a cont ralat eral hemiparesis including t he
low er port ion of t he f ace (Weber's syndrome). Likew ise, t he
presence of purposef ul movement s of t he hand associat ed w it h rest , post ural

and a vigorous kinet ic t remor (rubral t remor), w ould localize t he lesion near t he
red nucleus in t he midbrain.
I f t he pat ient present s w it h paraparesi s or parapl egi a, t he lesion can be locat ed
in t he cerebrum (e. g. , parasagit t al meningioma) or cervical or t horacic spinal
cord, or may be peripheral (e. g. , G uillain-Barré syndrome and bilat eral lumbar
plexopat hies). I n pat ient s present ing w it h quadri paresi s or quadri pl egi a, t he
low est level of cent ral nervous syst em pat hology is in t he high cervical cord
(quadriparesis can also be due t o diff use peripheral problems). Examinat ion of
t he muscle st ret ch ref lexes can be used t o f ind t he low est point at w hich t he
spinal cord pat hology can be locat ed. I n a spinal cord lesion, t he muscle st ret ch
ref lexes are lost at t he level of t he lesion and increased below t his level. As an
example, compression of t he low er cervical spinal cord causes low er mot or
neuron signs at t he corresponding segment al level and upper mot or neuron signs
below t he lesion (e. g. , spast ic paraplegia). Wit h C5 spinal cord segment lesions,
t he biceps ref lex (segment s C5–C6) and t he brachioradialis ref lex (segment s
C5–C6) are absent or diminished, w hereas t he t riceps ref lex (segment s C7–C8)
and t he f inger f lexor ref lex (segment s C8–T1) are exaggerat ed (see Chapt er 5).
O ccasionally, percussion of a t endon account s f or unexpect ed result s. I nvert ed
or paradoxical ref lexes result ing f rom combined spinal cord and root (e. g. ,
radiculomyelopat hy) pat hology show cont ract ions opposit e of w hat may be
expect ed. As an example, w it h a C5–C6 lesion, w hen t he biceps t endon is
t apped, t here is no biceps jerk, but t he t riceps cont ract (invert ed biceps ref lex).
Single limb w eakness may be due t o an upper mot or neuron lesion (e. g. , ant erior
cerebral art ery t errit ory inf arct ion and paracent ral lobule mass lesion) or an
ext ramedullary spinal cord lesion (e. g. , Brow n-Séquard syndrome, w here t here is
ipsilat eral low er mot or neuron paralysis in t he segment of t he lesion, ipsilat eral
spast ic paralysis below t he level of t he lesion due t o int errupt ion of t he
descending cort icospinal t ract , ipsilat eral loss of propriocept ive f unct ion below
t he level of t he lesion due t o int errupt ion of ascending f ibers in t he post erior
column, and cont ralat eral loss of pain and t emperat ure due t o int errupt ion of t he
crossed spinot halamic t ract ). How ever, w hen pat ient s present w it h an isolat ed
monoplegia and no involvement , even minor, of t he ot her limb or t he f ace, a
low er mot or neuron t ype of syndrome, at t ribut able t o a root , plexus, or nerve
lesion, must alw ays be considered.
A w ide range of condit ions can aff ect t he motor uni t. Lesions of t he low er mot or
neuron may involve t he mot or neurons, root s, plexus, peripheral nerves,
neuromuscular junct ion, and muscle and are discussed in det ail in subsequent
chapt ers. Muscle w eakness, at rophy, f asciculat ions, and exaggerat ed muscle
st ret ch ref lexes suggest mot or neuron disease (e. g. , amyot rophic lat eral
sclerosis). Diseases of t he peripheral nervous syst em may aff ect mot or,
sensory, or aut onomic neurons. Absent ref lexes are indicat ive of dysf unct ion of
large-diamet er sensory f ibers. How ever, t he pat ient 's age must be t aken int o
considerat ion because muscle st ret ch ref lexes diminish w it h advanced age. As an
example, an absent Achilles ref lex af t er age 80 may be a normal f inding[13] .
G eneralized dist al w eakness is likely t o be due t o a peripheral neuropat hy,
alt hough proximal w eakness occurs in some cases and can imit at e myopat hy.
Severe unilat eral pain made w orse w it h movement of t he arm, minor sensory
loss, w eakness more proximal t han dist al, and at rophy of muscles innervat ed by
t he upper t runk of t he brachial plexus suggest a diagnosis of Parsonage-Turner
syndrome or neuralgic amyot rophy. G eneralized proximal w eakness is likely t o
be due t o a myopat hy or neuromuscular junct ion disorder. Fluct uat ing w eakness
w it h a predilect ion f or t he ext raocular muscles and proximal limb muscles, w orse
w it h exercise and bet t er w it h rest , is t he hallmark of myast henia gravis.
Symmet ric upper and low er girdle muscle involvement associat ed w it h muscle
pain and dysphagia is of t en seen in pat ient s w it h idiopat hic inf lammat ory
myopat hies. Asymmet ric dist al (e. g. , f oot ext ensors and f inger f lexors) and
proximal (e. g. , quadriceps) w eakness may be a clue t o t he diagnosis of inclusion
body myosit is. Delayed relaxat ion of skelet al muscle f ollow ing volunt ary
cont ract ion is present in myot onic disorders. Episodic at t acks of f laccid limb
muscle w eakness, w it h sparing of ocular and respirat ory muscles, are
charact erist ic of periodic paralysis. Pseudohypert rophy of t he calves is seen in
most boys w it h Duchenne's muscular dyst rophy. The G ow ers' maneuver may be
observed, w it h aff ect ed pat ient s using t heir hands t o rise f rom t he ground.
The Localization of Sensory Abnormalities

Anatomy of the Sensory System
The peripheral sensory unit consist s of t he sensory recept or (each w it h a
charact erist ic modalit y and recept ive f ield), it s cont iguous axon, t he cell body in
t he dorsal root ganglion, t he dorsal root , and t he axonal t erminus in t he dorsal
horn or dorsal
column nuclei (depending on t he specif ic sensory syst em)[ 12] . Cut aneous
sensory aff erent f ibers are hist ologically divided int o C-t ype (small
unmyelinat ed), A-δ (small, t hinly myelinat ed), and A-α / β (myelinat ed).
FI G URE 1-3 A simplif ied diagram of t he somat osensory pat hw ays. (Adapt ed
f rom Brodal A. The somat ic aff erent pat hw ays. I n: Neurol ogi cal anatomy. In
rel ati on to cl i ni cal medi ci ne, 3rd ed. New York: O xf ord Universit y Press,
1981, w it h permission. )
The somat osensory pat hw ays are illust rat ed in Figure 1-3. Small lat eral group
f ibers (conveying pain, t emperat ure, and sof t t ouch) ent er t he spinal cord and
dichot omize int o collat erals, w hich ascend and descend one or t w o levels bef ore
synapsing in t he dorsal horn. The secondary sensory neurons decussat e in t he
ant erior commissure of t he spinal cord and t hen ascend in t he cont ralat eral
ant erolat eral f uniculi as t he spi nothal ami c tracts. Wit hin t he spinot halamic t ract ,
t he f ibers mediat ing sensat ion of pain and t emperat ure appear t o occupy t he
dorsolat eral part of t he ant erolat eral f uniculus and t hose conveying t he sensat ion
of t ouch are f ound in t he vent romedial part . The f ibers in t he spinot halamic t ract
are somat ot opically arranged. At cervical levels, f ibers f rom sacral segment s are
f ound most superf icially f ollow ed by f ibers originat ing at successively more
rost ral levels. I nt raparenchymal lesions of t he cord may t heref ore cause a loss
of sensat ion of pain, t emperat ure, and sof t t ouch below t he level of cord damage
but w it h sparing of sacral sensat ion (i. e. , “sacral sparing”). The somat ot opic
arrangement is maint ained during t he f urt her course of t he spinot halamic t ract in
t he medulla, pons, and midbrain, w it h t he t ract ending in t he t halamus,
predominant ly in t he vent ral-post erior-lat eral (VPL) nucleus, t he post erior
complex, and part s of t he int ralaminar nucleus.
Large medial group sensory f ibers (conveying propriocept ion, vibrat ory
sensat ion, deep pressure, and sof t t ouch) ent er t he w hit e mat t er closely medial
t o t he dorsal horn and ascend in t he posteri or col umn of t he spinal cord
ipsilat eral t o t heir corresponding nerve root and ganglion cells. These f ibers give
off f ew collat erals and t erminat e in t he nucleus gracilis and cuneat us in t he
caudal medulla oblongat a. During t heir ascending course, nerve f ibers in t he
dorsal columns are st eadily pushed more medially because f ibers ent ering at
succeeding rost ral levels int rude bet w een t he ascending f ibers and t he dorsal
horn. Theref ore, f ibers occupying t he most medial part of t he medial f uniculus
gracilis in t he upper cervical region w ill belong t o t he sacral dorsal root s, and
t hen f ollow t he f ibers f rom t he lumbar dorsal root s (i. e. , t he f ibers f rom t he
low er ext remit y are f ound more medially in t he dorsal columns). Fibers belonging
t o t he upper ext remit y are f ound more lat erally in t he f uniculus cuneat us, close
t o t he dorsal horn, w it h f ibers f rom t he upper cervical root s f ound more lat erally
t han t hose f rom low er cervical root s. O f t he t horacic f ibers, approximat ely t he
low er six occupy t he lat eral part of t he f uniculus gracilis; t he upper six occupy
t he medial part of t he f uniculus cuneat us. The ascending f ibers of t he dorsal
columns are t heref ore somat ot opically organized[12] .
The axons of t he cells of t he nuclei gracilis and cuneat us f orm t he medial
lemniscus, w hich crosses t he midline in t he medulla. The segment al somat ot opic
organizat ion present in t he dorsal columns and t heir nuclei are maint ained in t he
medial lemniscus[36] . I n t he medulla, t he f ibers of t he medial lemniscus, af t er
crossing, occupy a t riangular area dorsal t o t he pyramidal t ract . Here, f ibers
f rom t he gracile nucleus are sit uat ed vent rolat erally and t hose f rom t he cuneat e
nucleus dorsomedially. This same arrangement is maint ained in t he pons. Furt her
along t he t ract , a cert ain rot at ion t akes place, so t hat f ibers t hat w ere originally
vent rolat eral occupy t he lat eral posit ion, w hereas t he originally dorsomedial
f ibers f rom t he cuneat e nucleus are f ound medially. I n t his order, t he f ibers ent er
t he VPL nucleus of t he t halamus.
The pat hw ays f or joint posit ion sense and vibrat ion sense are probably more
complicat ed t han t he scheme provided in t he preceding t ext suggest s (Fig. 1-4)
[ 26] . G ilman review ed t he anat omic organizat ion of joint sense and vibrat ion
sensat ion and not ed t hat propriocept ion consist s of t he sense of posit ion and
movement of t he limbs and body in t he absence of vision[26] . Propriocept ion
includes t w o component s: t he sense of st at ionary posit ion of t he limbs (limb
posit ion sense) and t he sense of limb movement (kinest hesia). Each of t hese
component s can be t est ed individually. The primary aff erent f ibers innervat ing
muscle spindles provide t he principal recept ors f or bot h of t hese aspect s of
propriocept ion. Aff erent f ibers mediat ing propriocept ion ent er t he dorsal horn of
t he spinal cord and many of t hese aff erent s synapse w it h second-order neurons
in deeper layers of t he dorsal horn. Second-order neurons t hen ascend t hrough
t he ipsilat eral dorsolat eral f uniculus t o synapse in t he lat eral cervical nucleus
(LCN) locat ed in t he t w o upper cervical cord segment s, immediat ely vent ral t o
t he dorsal horn. Post synapt ic neurons t hen project across t he midline of t he cord
and ascend t o ent er t he medulla and join t he medial lemniscus. Some
propriocept ive aff erent s project direct ly int o t he dorsal columns and ascend t he
cord, t erminat ing in t he dorsal column nuclei. The dorsal columns (cuneat e and
gracile f ascicles), how ever, mediat e only t he discriminat ion of f requency and
durat ion of repet it ive t act ile st imuli. Most f ibers conveying propriocept ion f rom
t he
t runk and upper limbs t hat ent er t he cuneat e f asciculus run t heir f ull lengt h up t o
t he medulla in t his st ruct ure. I n cont rast , most f ibers conveying propriocept ion
f rom t he low er limbs depart f rom t he gracile f asciculus in t he upper lumbar cord
and t erminat e on t he neurons of Clarke's column; t hese neurons project t o
nucleus Z in t he medulla, and neurons f rom t his nucleus project t o t he medial
lemniscus w it h f ibers f rom t he cuneat e nucleus. The f ibers remaining in t he
gracile f ascicle principally cont ain t hese conveying t act ile sensat ion. Aff erent s
f rom t he dorsal columns synapse in t he dorsal column nuclei of t he medulla.
Axons f rom t he gracile and cuneat e nucleus f orm t he medial lemniscus, w hich
crosses t he midline and receives f ibers f rom t he LCN and nucleus Z. The medial
lemniscus ascends in t he brainst em t o t erminat e in t he VPL nucleus of t he
t halamus.
Vibrat ion sense is mediat ed by diff erent recept ors f rom propriocept ion[26] .
These recept ors include Merkel disk recept ors and Meissner's corpuscles.
Fibers mediat ing vibrat ion ent er t he cord and bif urcat e, w it h one branch
t erminat ing on neurons in t he deeper layers of t he dorsal horn and ot hers
ent ering t he dorsal columns. Second-order neurons f rom t he dorsal horn ascend
t hrough t he ipsilat eral dorsolat eral f uniculus, t erminat ing on neurons in t he LCN,
w hich in t urn project s f ibers
across t he cord midline t o ascend and join t he medial lemniscus in t he medulla.

O t her dorsal root collat erals ent er t he dorsal columns and ascend ipsilat erally,
t erminat ing in t he dorsal column nuclei. Furt her project ions f rom t hese pat hw ays
are t he same as t hose conveying propriocept ion, alt hough f ibers f or vibrat ion
and propriocept ion t erminat e in separat e dist ribut ions w it hin t he t halamus and
cerebral cort ex.
FI G URE 1-4 Diagram of t he peripheral recept ors and cent ral pat hw ays
mediat ing joint posit ion sense, vibrat ion sense, and t act ile sensat ion. The
low er diagram on t he right illust rat es t he recept ors principally responsible
f or posit ion sense, w hich are muscle spindle primary and secondary
aff erent s. The upper diagram on t he right illust rat es t he locat ion and
morphology of mechanorecept ors in glabrous (hairless) and hairy skin of t he
human hand. The recept ors are locat ed bot h in t he superf icial skin at t he
junct ion of dermis and epidermis and in t he deeper dermis and subcut aneous
t issue. G labrous skin cont ains Meissner's corpuscles, locat ed in dermal
papillae; Merkel disc recept ors, locat ed bet w een dermal papillae; and f ree
nerve endings. Hairy skin cont ains hair recept ors, Merkel recept ors, and f ree
nerve endings. Subcut aneous recept ors locat ed in bot h glabrous and hairy
skin include pacinian corpuscles and Ruff ini's endings. Merkel disc recept ors,
Meissner's corpuscles, and pacinian corpuscles are capable of mediat ing
vibrat ion sense, but pacinian corpuscles are responsible f or det ect ing
vibrat ion as t est ed clinically. Mult iple recept ors mediat e t act ile sensat ion,
including Meissner's corpuscles, Merkel discs, Ruff ini's endings, pacinian
corpuscles, and hair f ollicle recept ors. The diagram on t he lef t illust rat es t he
cent ral pat hw ays mediat ing joint posit ion sense, vibrat ion sense, and t act ile
sensat ion. Aff erent f ibers innervat ing pacinian corpuscles, muscle spindles,
and t act ile recept ors make synapt ic connect ions w it h dorsal horn neurons
t hat project rost rally t hrough t he dorsolat eral f uniculus (DLF) and t erminat e
in t he lat eral cervical nucleus (LCN) at spinal cord segment s C1 and C2.
Fibers f rom t he LCN project across t he midline and ascend int o t he medulla,
w here t hey join t he medial lemniscus. Some aff erent f ibers innervat ing t act ile
recept ors bif urcat e in t he dorsal horn, w it h one branch ent ering t he dorsal
columns (DCs) and t he ot her making a synapt ic connect ion on dorsal horn
neurons w it h axons t hat cross t he midline and project t hrough t he lat eral
spinot halamic t ract (not show n in t he diagram) or t he DLF. Fibers in t he DC
are laminat ed, w it h t hose f rom t he sacral region (S) most medial, and lumbar
(L), t horacic (T), and cervical (C) sequent ially more lat eral. DC f ibers f rom
sacral and lumbar segment s t erminat e in t he gracile (G ) nucleus and f ibers
f rom t horacic and cervical segment s t erminat e in t he cuneat e (C) nucleus of
t he medulla. Fibers project ing f rom t he G and C nuclei pass across t he
midline and ent er t he medial lemniscus, w hich ascends t o t he vent ral-
post erior-lat eral (VPL) nucleus of t he t halamus. Thalamocort ical f ibers f rom
VPL project t o t he primary somat osensory cort ex (S1) of t he post cent ral
gyrus. ML = medi al lemniscus, LS = l ateral sulcus, CT. (From: G ilman S.
Joint posit ion sense and vibrat ion sense: anat omical organizat ion and
assessment . J Neurol Neurosurg Psychi atry 2002; 73(5): 473–477, w it h
permission. )
From t he t halamus, t he sensory impulses are conveyed mainly t o t he

somat osensory areas of t he cerebral cort ex (e. g. , t he post cent ral gyrus). Wit hin
t he somat osensory cort ex, t here is a somat ot opic organizat ion. For example, in
t he post cent ral gyrus, t he calf and f oot are represent ed on t he medial surf ace of
t he hemisphere, f ollow ed by t he t high, abdomen, t horax, shoulder, arm, f orearm,
hand, digit s, and f ace. Theref ore, a parasagit t al lesion may cause sensory
changes conf ined t o t he low er limb.
Sensory Signs and Symptoms and Their Localization

Sensory sympt oms may be posit ive or negat ive. Posit ive sympt oms include
paresthesi as, w hich are spont aneous sensat ions occurring w it hout st imulat ion.
Hyperesthesi a ref ers t o exaggerat ed sensat ion, dysesthesi a t o alt ered
sensat ion, al l odyni a t o a painf ul response t o nonnoxious st imulat ion, and
hyperpathi a t o exaggerat ed sensat ion t o a painf ul st imulus. Hypest hesia is
decrease in sensat ion, w hereas anest hesia is complet e loss of sensat ion; bot h
may occasionally be associat ed w it h pain (anesthesi a dol orosa). Propriocept ive
impairment may cause at axia and pseudoat het osis.
The localizat ion of lesions aff ect ing t he somat osensory pat hw ays is out lined in
Table 1-2.
Localization of Postural and Gait Disorders

Bot h t he sensory and mot or syst ems play a crucial role in t he maint enance of a
st able st ance, w hich w e w ill ref er t o here simply as posture, and in t he
mediat ion of gait . I t is how ever w ort h summarizing separat ely t he localizat ion of
disorders of post ure and gait because t hey are f requent and require a slight ly
diff erent approach. Post ure and gait are complex f unct ions t hat require input
f rom t he nervous syst em but can also be alt ered by t he disorders of
nonneurologic st ruct ures, including t he muscles and joint s. O f t en clinical bias
t ends t o f avor a nonneurologic diagnosis w hen t he problem is act ually in t he
neural cont rol of gait or post ure. Alt hough init iat ed and modif ied volit ionally, bot h
f unct ions run largely in t he background. For inst ance, w hen concent rat ing on
get t ing somet hing
f rom t he ref rigerat or, a person pays no at t ent ion t o t he complex movement s of
t he legs and paravert ebral muscles w hile w alking. Likew ise, t he person is not
aw are of t he movement s t he same muscles make w hen shif t ing in bed, an
act ivit y mediat ed by similar neural st ruct ures.
TABLE 1-2 The Localization of Lesions Affecting the

Somatosensory Pathw ays
Location of
Clinical Findings
Lesion
Sensory symptoms mainly in the

distribution of sensory supply of
nerve, but may radiate beyond the
distribution of the damaged nerve
Peripheral nerve
Sensory loss generally confined to
(mononeuropathy)
the area supplied by the nerve
In general, the area of light touch
loss is greater than the area of
pain loss
Usually distal symmetric sensory

loss (e.g., feet)
Rare proximal sensory loss (e.g.,
proximal sensory neuropathy with
porphyria or Tangier disease)
Rare temperature-related sensory
loss (e.g., leprosy)
Polyneuropathy
Sensory loss progresses according
to axonal length
Sensory loss may preferentially
affect certain modalities depending
on the etiology (e.g., small fiber
sensory loss with primary
amyloidosis)
Similar to dorsal root lesion

Diffuse involvement with dorsal
root ganglionopathy (e.g., due to
Dorsal root
remote effect of cancer or
ganglion
Sjögren's syndrome)—diffuse
pansensory loss with sensory
ataxia
Irritative symptoms (e.g., radicular

pain or paresthesias) and sensory
loss in dermatomal (i.e.,
segmental) distribution
Because of overlap of innervation,
interruption of one thoracic or
Dorsal root upper lumbar dorsal root may give
rise to sensory symptoms without
definite sensory loss
Sensory loss to touch may extend
over larger territory than pain and
temperature loss
Dorsal horn or central gray matter

lesion produces the same
ipsilateral segmental sensory
disturbance as dorsal root lesion;
segmental sensory loss “marks”
the level of cord involvement
Lesion of anterolateral funiculus
causes loss of pain and
temperature sense on the
contralateral side of the body at all
levels caudal to the site of lesion;
upper border of the sensory loss
approximately corresponds to the
lower border of the dermatome
belonging to lowest preserved cord
segment
If the lesion is limited to more
superficial parts of tract, a more
Spinal cord restricted sensory loss occurs,
with upper segment of sensory
loss found several segments
farther caudally; the more so, the
more superficial the lesion
If the lesion is deep and spares
superficial fibers, sensory loss
may “spare” the distal segments
(e.g., “sacral sparing”)
Lesion of the dorsal funiculus
causes loss of vibratory and
position sense and sensory ataxia
below the involved segment
ipsilateral to the lesion
Brown-Séquard (hemicord)
syndrome (see Chapter 5)
Central cord lesion (e.g.,
syringomyelia)—dissociation of
sensory loss (see Chapter 5)
Association of sensory
abnormalities with other medullary
signs and symptoms (e.g., CN XII
paresis)—often “crossed” findings
(CN palsy on one side of the face
and sensory or motor loss on the
opposite side of the body)
LAT ERAL MEDULLA
Loss of pain and temperature on
the contralateral side of the body,
may spare medial lemniscus
functions
Frequently associated with
involvement of the spinal tract and
Medulla nucleus of CN V—decreased pain
oblongata and temperature on the ipsilateral
face and contralateral body
(hemianesthesia alternans)
Medial m edulla
Impairment of vibratory and
position sense on opposite side of
the body, may spare the
spinothalamic tract
Often associated with ipsilateral
CN XII paresis
Because of somatotopic
organization, there may be
sensory changes “below a level” or
“to a level” mimicking spinal cord
involvement
Similar to the sensory changes

outlined under medullary lesion but
Pons associated with pontine CN signs
and symptoms (e.g., horizontal
gaze palsies)
Similar to the sensory changes

outlined under medullary lesions
Midbrain but associated with midbrain CN
signs and symptoms (e.g., vertical
gaze palsies)
Lesion of VPL nucleus results in

sensory loss to all modalities on
the opposite side of the face and
Thalamus
body
Somatotopic localization exists in
the thalamus
Circumscribed lesion of the

postcentral gyrus causes localized
sensory loss in part of the
Cerebrum opposite half of the body (e.g.,
lesion of parasagittal postcentral
gyrus causes sensory changes in
opposite leg)
CN = cranial nerve; VPL = ventral-posterior-lateral.
Neurologic disorders of gait and post ure can be localized using t w o main
approaches:
1. Characteri zati on of the gai t di sorder the pati ent has. I n ot her w ords, w e
st udy how t he pat ient w alks or st ands, or moves in bed, and f rom t he pat t ern
of movement or post ure, w e t ry t o ident if y t he lesioned st ruct ures. Some
t ypes of gait , such as t he hemiparet ic gait , are highly st ereot ypic and def ine
t he cause as damage t o a specif ic st ruct ure (e. g. , t he cort icospinal t ract in
t he case of hemiparesis). O t her t ypes of gait , such as t he caut ious gait or
cent ral disequilibrium, may have many diff erent et iologies and t he lesion
causing it is more diff icult t o localize.
2. Identi f i cati on of accompanyi ng neurol ogi c si gns. Many lesions causing
neurologic gait disorders also cause ot her neurologic f indings t hat may be
helpf ul in localizing t he lesion. I n t he case of t he hemiparet ic gait , w e may
f ind a Babinski's sign point ing t o a lesion in t he cort icospinal t ract . Many
st ruct ures of t he nervous syst em part icipat e in t he cont rol of gait , as
indicat ed in t he subsequent t ext . The signs or sympt oms caused by lesions
of t hese st ruct ures are described in t he rest of t he book.
Neural Structures Controlling Posture and Gait

At t he simplest level of analysis, t he act of st anding and w alking requires
sensory inf ormat ion reaching specif ic brain cent ers and a mot or out put f rom
t hese cent ers[46, 47] . Sensory inf ormat ion includes propriocept ion, vision, and
vest ibular input . Some brain cent ers import ant f or post ure are
t he vest ibular nuclei, t he medullary and pont ine ret icular f ormat ion, t he
pedunculopont ine nucleus (at t he junct ion bet w een t he pons and midbrain), and
t he subst ant ia nigra (in t he midbrain). The cerebellum, basal ganglia, and
t halamus play a major role in t he cent ral cont rol of gait . I n humans, t he medial
f ront al cort ex, part icularly t he SMA and t he paracent ral lobule, also cont ribut e t o
t he cont rol of gait . O n t he mot or side, t he cort icospinal, vest ibulospinal, and
ret iculospinal t ract s, among ot hers, convey out put f rom higher cent ers t o t he
spinal cord. I n t urn, t he ant erior horn cells, t hrough t heir axons, st imulat e
muscles t hat t urn t his out put int o specif ic movement s.
Examination of Gait and Balance
I f a pat ient can st and f rom a low chair w it hout using his or her arms, w alk
normally, maneuver t urns w ell, w alk on his or her heels and in t andem, and is
st eady w it h eyes closed and f eet t oget her and denies any imbalance or t endency
t o f all, gait and balance are probably normal. When examining a child, ask him or
her t o run f or a brief st ret ch, w hile dist ract ing f rom t he act ion of running by
asking t o come and get somet hing. I f any abnormalit y is suspect ed f rom t hese
screening maneuvers, t he neural syst ems involved in gait should be t est ed
f urt her. Sensory syst ems can be t est ed by exploring t he perf ormance of t he
pat ient w hen one or t w o variet ies of sensory input are removed and t he post ural
ref lexes depend on t he remaining sensory inf ormat ion. For inst ance, t he
Romberg t est explores t he pat ient 's abilit y t o maint ain a st eady upright post ure
w it h vision removed and t he base of support reduced by keeping t he f eet
t oget her. Propriocept ive or vest ibular loss w ill result in diff icult y maint aining
balance. To t est t he int act ness of t he cort icospinal t ract , spinal cord, peripheral
nerves, and muscles, t he pat ient is asked t o w iggle t he t oes, draw a circle on
t he f loor w it h each f oot , and t o ext end t he big t oe against resist ance. Proximal
muscle st rengt h in t he legs can be t est ed by asking t he pat ient t o rise f rom a
low chair w it hout using his or her arms t o prop himself or herself up. Despit e t he
pat ient 's abilit y t o complet e all t hese t asks quit e w ell, t here may st ill be diff icult y
in w alking and a propensit y t o f all. This apparent discrepancy highlight s t he
import ance of neural syst ems crit ical f or post ure, w hich are dist inct f rom t he
syst em mediat ing volit ional leg and f oot movement s[46] .
For t he descript ion of gait disorders and t heir localizat ion, w e w ill f ollow a
classif icat ion reminiscent of t he one by Marsden and Thompson[38] and Nut t et
al. [ 48] . They considered gait disorders in t erms of t he hierarchy of low er,
middle, and higher sensorimot or levels.
Sensory and Lower Motor Gait Disorders

These disorders occur w it h myopat hies or lesions of t he peripheral nervous
syst em or t heir nuclei of origin, part icularly in younger pat ient s. When a sensory
syst em is aff ect ed in isolat ion, t he disorder is seldom long last ing. Blind people,
t hose w it h bilat eral dest ruct ion of t he semicircular canals, and t hose w it h
prost het ic limbs can w alk. The int act cent ral mechanisms use t he inf ormat ion
arriving f rom t he ot her sensory syst ems t o event ually compensat e f or t he single-
modalit y sensory loss. The problem can be more devast at ing w hen mult iple
sensory syst ems are aff ect ed.
Steppage Gait
Severe deaff erent at ion or a bilat eral f oot drop may result in an excessive f lexion
of t he hips and knees w it h every st ep. Wit h sensory loss, t he heel t ends t o st rike
t he ground heavily. The great er f oot clearance is used t o prevent t he pat ient
f rom t ripping on t he t oes or on t he f loor irregularit ies t hat are poorly f elt . The
most common cause of t his problem is severe t hick-f iber neuropat hy of t he kind
encount ered w it h t he G uillain-Barré syndrome and ot her demyelinat ing
neuropat hies, including heredit ary disorders such as Charcot -Marie-Toot h
disease.
Vestibular Ataxia
Acut e vest ibular lesions cause inst abilit y and a t endency f or t he pat ient t o veer
or even f all t o t he side of t he lesion. The base of support is w idened and
perf ormance is markedly degraded by t he Romberg's maneuver or w hen t he
pat ient is asked t o w alk w it h eyes closed.
Visual Ataxia
Acut e dist ort ion of visual percept ion can lead t o at axia, w it h a broad base of
support and t ent at ive st eps. I n t he past , t his t ype of gait diff icult y w as common
af t er cat aract surgery, w it h removal of t he aff ect ed lens leaving t he pat ient w it h
a severe ref ract ive def ect . Lens replacement has reduced t he incidence of t his
problem.
Waddling Gait
The w addling gait is seen w it h severe proximal muscle w eakness. Weakness of
t he hip muscles, part icularly t he glut eus medius, result s in an excessive drop of
t he hip and t runk t ilt ing t o t he side opposit e t he f oot placement . The hips
oscillat e up and dow n w it h every st ep, making t he
pat ient seem t o w addle. Wit h muscle w eakness, t here is accent uat ion of t he
lumbar lordosis.
Simpler Gait Disorders of Central Origin

Simpler gait disorders of cent ral origin f ollow lesions locat ed more cent rally t han
t he ones causing sensory and low er mot or gait disorders. Disorders of
pyramidal, cerebellar, or nigral mot or syst ems cause dist ort ion of appropriat e
post ural and locomot or synergies[38] . I n general, t he correct post ural and
locomot or responses are select ed, but t heir execut ion is f ault y.
Spastic Gait
Cort icospinal t ract lesions give rise t o a spast ic gait , unilat eral or hemiparet ic
w hen t he lesion is unilat eral and paraparet ic w hen t he lesion is bilat eral. The
base of support is narrow, so much so t hat w it h bilat eral lesions t he legs t end t o
cross in f ront of each ot her in a pat t ern t hat has been called “sci ssors gai t. ” The
leg is ext ernally rot at ed at t he hip. The knee is ext ended and st iff , so t he pat ient
w alks as if on a st ilt . The f oot is plant ar f lexed and invert ed; f or t his reason, t he
pat ient t ends t o scrape t he f loor w it h t he out er edge of t he f oot ; t he pat ient 's
t urns are slow. There is also diff icult y picking up t he t oes on t he hemiparet ic
side, w hen inst ruct ed t o w alk on t he heels. The lesion can be anyw here along
t he cort icospinal t ract . When t he lesion is unilat eral, t he abnormalit y is easy t o
diagnose. Bilat eral lesions, part icularly w hen t hey cause a slow ly progressive
syndrome, are more diff icult t o diagnose early in t he course of t he disease. The
cervical myelopat hy of cervical spondylosis, a relat ively common syndrome,
belong t o t his cat egory. Cervical spondylosis t ends t o cause demyelinat ing
lesions in t he post erior columns and cort icospinal t ract s of t he cervical spinal
cord. The most common place of involvement is at t he C5–C6 int erspace. Severe
lesions in t his locat ion result in paraparesis and clumsiness of t he hand w it h
at rophy in t he small muscles of t he hand. Milder lesions may only give rise t o
unst eadiness w hile w alking or st anding, of t en accompanied by a posit ive
Romberg's sign[37] . The brachioradialis ref lex may be depressed, and inst ead, a
brisk f inger f lexor response is elicit ed w hen percussing t he brachioradialis
t endon (i nverted radi al ref l ex). Caref ul t est ing of vibrat ory sense may reveal a
sensory level in t he cervical region. Somet imes t he pat ient perceives t he
st imulus bet t er in t he t humb t han in t he small f inger. Early diagnosis is import ant
because t he myelopat hy of cervical spondylosis is of t en progressive if
unt reat ed[ 50] .
Cerebellar Ataxic Gait

Lesions of t he ant erior lobe of t he cerebellum can also be accompanied by a
discret e impairment in gait , and t hose aff ect ing t he f locculonodular lobe aff ect
equilibrium[ 25] . Cerebellar lesions may aff ect gait by causing disequilibrium and
by alt ering limb and t runk kinemat ics and int erlimb coordinat ion[16] . The
cerebellum does not appear t o act ually generat e post ural and gait synergies
because t hese aut omat ic responses, albeit very dysmet ric, are present in dogs
w it h t ot al cerebellect omy[49] . Dist urbances of gait and balance are primarily
caused by lesions of t he vest ibulocerebellum and spinocerebellum or t heir
connect ions. Lesions of t he cerebellar hemispheres cause irregular t iming, f orce,
and cadence of leg movement s, leading t o inaccurat e and variable st epping[28] .
Lesions of t he vesti bul ocerebel l um, or f locculonodular lobe, can produce
balance and gait dist urbances t hat resemble t hose caused by vest ibular
lesions[ 16] . Tremor of t he head and t runk, t runcal imbalance, and sw aying and
f alling in all direct ions are charact erist ic of vest ibulocerebellar lesions.
Vest ibular nyst agmus may be present . Alt hough most of t en pat ient s w it h
cerebellar lesions t end t o f all t o t he side of t he lesion, some pat ient s w it h
lesions in t he t onsillar area develop increased t one (and increased ref lexes) in
t he ipsilat eral side and f all t o t he cont ralat eral side.
The clinical syndrome caused by lesions of t he spi nocerebel l um is best
charact erized by alcoholic cerebellar degenerat ion, w hich primarily aff ect s t he
ant erior lobe of t he cerebellum but also involves t he olivary complex and t he
vest ibular nuclei[60] . Pat ient s w it h alcoholic cerebellar degenerat ion have a
w idened base, inst abilit y of t he t runk, slow and halt ing gait w it h irregular st eps
and superimposed lurching. The gait abnormalit ies are accent uat ed at t he
init iat ion of gait , on t urning, and w it h changes in gait speed. These pat ient s may
have severe gait at axia w it hout nyst agmus, dysart hria, or arm dysmet ria. Even
t he heel-t o-shin t est may give lit t le inkling of t he severit y of t he gait dist urbance.
The ant erior lobe of t he cerebellum is exquisit ely sensit ive t o many met abolic
injuries, not just alcohol. For inst ance, in severe hypoxia, t he ant erior lobe can
be severely damaged, w hereas t he rest of t he cerebellum may be spared.
Parkinsonian Gait
The pat ient w it h Parkinson's disease w alks w it h a rigid t runk, reduced arm
sw ing, slow and short st eps, and a t endency f or t he knees t o be f lexed. The gait
of pat ient s w it h classical Parkinson's
disease diff ers f rom t he gait of pat ient s w it h t he at ypical parkinsonian

syndromes, such as progressive supranuclear palsy. Festi nati on, a t endency f or
t he pat ient t o begin running af t er t aking a f ew st eps, may be present w it h
classical Parkinson's disease, but seldom w it h at ypical Parkinson's syndrome.
The base of support is generally normal in early Parkinson's disease but is of t en
w idened in at ypical Parkinson's disease, w hich is also of t en accompanied by
impaired balance. Whereas a st oop is charact erist ic of classical Parkinson's
disease, pat ient s w it h progressive supranuclear palsy w alk quit e erect . Early
reduct ion of arm sw ing is more charact erist ic of classical Parkinson's disease.
This disease f ollow s dest ruct ion of neurons of t he subst ant ia nigra. The
parkinsonian syndromes are caused by more w idespread lesions, some of w hich
involve t he lent icular nucleus.
Choreic, Hemiballistic, and Dystonic Gaits

I n choreic, hemiballist ic, and dyst onic gait s, t he abnormal choreic, hemiballist ic,
or dyst onic movement s are superimposed t o t he normal gait . Whereas chorea or
hemiballismus usually int erf eres lit t le w it h t he abilit y t o w alk, dyst onia can cause
severe gait diff icult ies. I nt orsion of t he f oot is a relat ively common dyst onic
movement in pat ient s on dopaminergic agent s. Chorea is most f requent , w it h
lesions of t he ant erior put amen result ing in an excessive suppression of t he
inhibit ory act ivit y of t he globus pallidus medialis over t he lat eral t halamus.
Hemiballismus, most pronounced in t he leg w hile t he pat ient is sit t ing or lying
dow n, abat es part ially in t he low er ext remit y w hen t he pat ient begins t o w alk. I t
is due t o a lesion of t he subt halamic nucleus. Dyst onia can be f ound w it h
lent icular nucleus lesions[6] .
Complex Gait Disorders of Central Origin

Complex gait disorders of cent ral origin are less w ell charact erized t han t he
ones previously described. Nonet heless, t hey are probably more common,
part icularly in t he elderly populat ion. I n some cases, t hey are caused by lesions
of brainst em nuclei. Some ot hers are due t o damage of t he cont rol loop t hat
begins in t he paracent ral cort ex and PMC and project s t o t he put amen. Through
direct and indirect pat hw ays, modif ied by input f rom t he subst ant ia nigra and
subt halamic nucleus, t he put amen project s t o t he medial globus pallidus, w hich
inhibit s t he act ivit y of t halamic neurons in t he vent rolat eral and vent ral ant erior
nuclei. These t halamic nuclei project back t o t he f ront al cort ex. This loop
probably plays an import ant role in mediat ing overlearned, unconscious mot or
act ivit y t hat runs in t he background, such as gait and post ural ref lexes. Pat ient s
w it h lesions in t his loop can markedly improve t heir gait by paying at t ent ion t o it .
They have a f ault y “aut omat ic pilot ” f or post ural ref lexes. Finally, ot her gait
disorders result f rom direct dysf unct ion of t he cort ex in t he post erior port ion of
t he medial f ront al region.
The Cautious Gait

The caut ious gait is charact erized by a normal or mildly w idened base, a
short ened st ride, slow ness of w alking, and t urning en bl oc[ 38, 54] . Anyone w ho
has t o w alk on an icy st reet may have adopt ed a similar gait pat t ern t o minimize
t he risk of f alling. Wit h t his gait st rat egy, t he cent er of gravit y remains w it hin t he
limit s of t he base of support . This gait disorder is seen mainly in older people. I t
may represent a milder or compensat ory phase of any of t he disorders causing
poor balance and is not localizing.
Brainstem Disequilibrium
To a lesser or great er degree, pat ient s w it h brainst em disequilibrium have poor
equilibrium. Some may f eel unst eady, alt hough t here is lit t le evidence in t he
neurologic examinat ion. O t hers are so unst eady t hat t hey cannot st and or even
sit up unassist ed.
I t is w ell know n t hat damage of t he vesti bul ar nuclei can result in marked
impairment in equilibrium, w it h a t endency t o f all t o t he side of an acut e injury.
Milder vest ibular dysf unct ion may be an import ant cause of gait dist urbances in
older people w it hout overt vest ibular disease[17] . Fif e and Baloh f ound vest ibular
dysf unct ion in 26 pat ient s older t han 75 years w ho complained of disequilibrium
and in w hom no cause w as evident af t er clinical evaluat ion. Alt hough none had
Romberg's sign, t he pat ient s t end t o sw ay more and do poorer on
semiquant it at ive gait and balance t est ing t han t he cont rols did. Their base of
support w as slight ly w idened, t heir t urns unst eady, and t hey had a t endency t o
st agger w hen pushed and veer w hen w alking.
I n pat ient s w it h at herosclerosis, isolat ed ponti ne hyperint ense lesions on MRI
correlat ed w it h disequilibrium[33] . The lesions w ere locat ed in t he basis pont is,
possibly involving t he cort icopont ine or cort icospinal f ibers, t he pont ocerebellar
f ibers, and t he pont ine nuclei. The rest of t he brain appeared normal on MRI .
Pyramidal signs w ere equally dist ribut ed among pat ient s and cont rols[33] .
The lat erodorsal region of t he mi dbrai n cont ains t he mesencephalic locomot or
region, w hich plays an import ant role in locomot ion in animals [23] . St imulat ion of
t his region in t he cat induces rapid w alking, f ollow ed by running. This area
cont ains t he nucleus cuneif ormis and t he cholinergic pedunculopont ine nucleus. I n
humans, loss of neurons in t he pedunculopont ine nucleus has been f ound in
pat ient s w it h progressive supranuclear palsy and Parkinson's disease but not in
pat ient s w it h Alzheimer's disease, perhaps implying a role of t his nucleus in
ambulat ion[ 64] . Discret e vascular damage in t his region can give rise t o severe
disequilibrium and a loss of rhyt hmic, alt ernat ing f eet movement t hat
charact erize normal w alking[41] . I t is conceivable t hat ot her brainst em nuclei,
st ill poorly ident if ied, may also play an import ant role in post ural mechanisms.
Disequilibrium With “Automatic Pilot” Disorder

The disorders described next are charact erized not only by disequilibrium but
also by a st riking diff erence bet w een t he pat ient s' perf ormance w hen t hey w alk
spont aneously and a bet t er perf ormance w hen t hey t hink about w alking, f or
inst ance, by st epping over an obst acle or t rying t o t ake long st rides. All of t hese
lesions aff ect t he cort icobasal ganglionic-t halamo-cort ical loop, described at t he
beginning of t his sect ion. The basal ganglia are part of an import ant loop t hat
cont rols proximal movement s part icipat ing in post ural synergies.
1. Basal gangl i a l esi ons. Early disequilibrium charact erizes progressive

supranuclear palsy and mult iple syst em at rophy and helps diff erent iat e t hem
f rom early Parkinson's disease. Acut e lesions of t he basal ganglia can also
produce a syndrome of unst eadiness w it hout t he loss of isomet ric pow er, in
w hich a pat ient w it hout an apparent w eakness cannot st and normally[34] .
2. Thal ami c l esi ons. Whereas chronic lesions of t he basal ganglia are bet t er
know n t o cause axial mot or impairment t han acut e ones, t he opposit e is t rue
f or t halamic lesions. A syndrome of impaired axial post ural movement s has
been described w it h acut e inf arct ion or hemorrhage in t he vent rolat eral
nucleus of t he t halamus or suprat halamic w hit e mat t er[42] . Alt hough alert ,
w it h normal or near normal st rengt h on isomet ric muscle t est ing and a
variable degree of sensory loss, t hese pat ient s could not st and, and some
w it h acut e lesions could not sit up unassist ed f or several days af t er t he
acut e insult . They f ell backw ards or t ow ard t he side cont ralat eral t o t he
lesion. These pat ient s appeared t o have a def icit of overlearned mot or
act ivit y of an axial and post ural nat ure. The syndrome has been called
thal ami c astasi a and grouped by some among t he cent ral disequilibrium
syndromes[ 48] .
3. Hemi spheri c paracentral peri ventri cul ar whi te matter l esi ons. The out put of
t he t halamus t hat is crit ical f or gait is direct ed t o t he areas of t he cort ex
involved in low er ext remit y movement s. This area of t he cort ex is t he medial
f ront al region, specif ically, t he paracent ral lobule and t he SMA. The f ibers
reaching t his area f rom t he t halamus course t hrough t he perivent ricular w hit e
mat t er. Theref ore, it is possible or even likely, t hat lesions in t his area may
result in impaired gait . I schemic disease of t he w hit e mat t er is common in
t he elderly populat ion. Beginning w it h a report in 1989, many st udies have
conf irmed t hat w hit e mat t er abnormalit ies on comput ed t omography scan and
MRI correlat e w it h impaired gait and balance in older people[3, 14, 43] . The
kind of gait impairment seen in t hese pat ient s corresponds t o w hat has been
t ermed t he cauti ous gai t[ 54] . Because t he pat ient s have poor balance, t he
st eps are short er, possibly t o lessen t he single-f oot st ance port ion of t he
gait cycle. Like pat ient s w it h t halamic lesions, t hese individuals may seem t o
w alk rat her normally so long as t hey pay at t ent ion t o t heir gait . How ever,
w hen t hey engage t he “aut omat ic pilot , ” and t he mot or cont rol syst em begins
t o be relied on f or involunt ary movement s, t hey t end t o f all. Sudden buckling
of t he knees may precipit at e t hem t o t he f loor.
Disequilibrium may also be prominent in pat ient s w it h hydrocephalus and w it h

lesions in t he medial aspect of t he f ront al lobe. How ever, t hese pat ient s t end t o
have t he gait disorder described in t he subsequent t ext as “magnet ic gait . ”
Cent ral disequilibrium is probably t he most common cause of t he so-called drop
at t acks, sudden f alls w it hout w arning or loss of consciousness in older
individuals. Drop at t acks w ere originally at t ribut ed t o t he disease of t he
vert ebrobasilar syst em, but t his et iology of drop at t acks in t he elderly is
probably not as common as subcort ical hemispheric disease[40] .
Isolated Gait Ignition Failure

Wit h preserved balance, pat ient s w it h isolat ed gait ignit ion f ailure cannot st art
w alking because of hesit at ion and may f reeze in t he course of locomot ion,
part icularly on a t urn[38, 48] . O nce t he pat ient begins t o w alk, st eps are short
and shuff ling,
but t hey become larger and t he f oot clearance increases as t he pat ient cont inues
t o w alk. The base of support is normal. Post ural responses are preserved. Eye
closure does not induce abnormal sw aying. Maneuvers t hat bring about a
“cort ical st rat egy, ” such as t rying t o kick an imaginary ball, st ep over a cane, or
count t he st eps, help t he pat ient init iat e and maint ain gait . Minus t he
disequilibrium, t his disorder mimics t he “aut omat ic pilot disorder” described in
t he previous sect ion. The anat omic localizat ion of t his disorder is st ill undef ined,
but involvement of f ront obasal ganglionic mechanisms is suspect ed because it
shares t he f eat ures of t he parkinsonian gait and t he magnet ic gait described
next .
M agnetic Gait
Magnet ic gait is a disorder t hat corresponds t o w hat Nut t et al. call f rontal gai t
di sorder and ot hers have described as marche à peti t pas or arteri oscl eroti c
parki nsoni sm[ 48] . Meyer and Barron called it apraxi a of gai t because despit e
t he severe gait disorder t he pat ient s can move t heir legs at w ill[44] . Alt hough
able t o st and, t hese pat ient s have such an inabilit y t o lif t t heir f eet and w alk t hat
t heir f eet may seem t o be glued t o t he f loor. Some pat ient s have great diff icult y
init iat ing w alking and, w hen pushed f orw ard, t he heels are lif t ed but t he t oes
seem t o grab t he f loor. There may be a dissociat ion bet w een gait and dist al
volit ional movement s, in t hat t he pat ient s may be quit e able t o draw f igures w it h
t heir f eet or do t he heel–shin maneuver normally. G iven t he preservat ion of even
complex mot or pat t erns f or t he low er ext remit ies, it is perhaps bet t er t o not use
t he t erm apraxi a f or t his t ype of gait . Milder f orms of t he same disorder
resemble t he parkinsonian gait , w it h short , shuff ling st eps and t runcal rigidit y.
Arm sw ing during w alking may be preserved and, if so, helps diff erent iat e t his
disorder f rom Parkinson's disease[58] . The t urns are very slow and broken dow n
int o many st eps. Turning may bring up t he t endency f or t he f eet (or f or one f oot
more t han t he ot her w hen t he problem is asymmet rical) t o become glued t o t he
f loor. Freezing may become evident as t he st eps halt and t he pat ient remains
mot ionless or develops t remor-like movement s of t he low er legs. Falls are
common, part icularly in pat ient s w ho have disequilibrium. This disorder may be
caused by bilat eral lesions of t he medial f ront al cort ex, severe hydrocephalus, or
bilat eral ischemic lesions of t he w hit e mat t er. G ait impairment is part of t he
classical t riad f or t he diagnosis of normal-pressure hydrocephalus[1] . Some
aut hors have described t his ent it y as a rat her prevalent cause of gait disorders
in t he aging populat ion[19] . How ever, ot her st udies, looking at t he out come of
shunt ing f or large vent ricles in older individuals, have concluded t hat t his is a
relat ively rare ent it y[27] .
Disequilibrium and Disorganized Gait

Disequilibrium and disorganized gait is a disorder t hat corresponds t o w hat Nut t
et al. ref er t o as f rontal di sequi l i bri um[ 48] . There is disequilibrium and a
disorganizat ion of gait pat t erns, such t hat t he pat ient s do not move t he legs
appropriat ely f or locomot ion. They may cross t he legs or move t hem in direct ions
t hat are inappropriat e t o keep balance or even t o sit up f rom a sit t ing posit ion.
This disorder has been described w it h a variet y of f ront al lobe lesions[48] and
also w it h lesions in t he mesencephalic locomot or cent er[41] .
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> Table of C ontents > C hapter 2 - P er ipher al Ner ves
Chapter 2
Peripheral Nerves
Principal Signs and Symptoms of Peripheral Nerve

Disease
Disorders aff ect ing mixed peripheral nerves cause various sympt oms and signs
corresponding, in anat omic dist ribut ion, t o regions supplied by each nerve. To
make a correct t opographic diagnosis of peripheral nerve lesions, t he clinician
must t horoughly know t he area of t he sensory supply of each nerve, t he muscles
it innervat es, and any muscle st ret ch ref lex subserved by t he nerve[339] . Cert ain
nerves are purely mot or, some are purely sensory, and ot hers are mixed. The
sympt oms and signs of a peripheral nerve lesion include dist urbances as det ailed
in t he f ollow ing t ext .
Sensory Disturbances
Wit h t he division of a sensory nerve, all modalit ies of cut aneous sensibilit y are
lost only over t he area exclusively supplied by t hat nerve (t he aut onomous zone).
This zone is surrounded by an int ermediat e zone, w hich is t he area of t he nerve's
t errit ory overlapped by t he sensory supply areas of t he adjacent nerves. The f ull
ext ent (aut onomous plus int ermediat e) of t he nerve's dist ribut ion const it ut es t he
maximal zone. I n clinical diagnosis, t he aut onomous zone of sensory loss f or
each nerve must be specif ically sought t o make an accurat e t opographic
localizat ion. I n general, w it h peripheral nerve lesions, t he area of light t ouch
sensory loss is great er t han t he area of pinprick sensory loss.
Pain and parest hesias may also help in localizing a peripheral nerve lesion, but
t hese subject ive sensat ions f requent ly radiat e beyond t he dist ribut ion of t he
damaged nerve (e. g. , proximal arm pain in t he carpal t unnel syndrome). Some
pat ient s describe pain t hat is evoked by nonnoxious st imulat ion of t he skin
innervat ed by a damaged nerve (allodynia).
Motor Disturbances
I nt errupt ion of t he mot or f ibers in a mot or or mixed nerve leads t o low er mot or
neuron paresis or paralysis of t he muscles innervat ed by t hat nerve. At rophy of
specif ic muscle groups and charact erist ic def ormit ies f ollow. The muscle or
muscle groups involved may become f laccid (hypot onic), w it h decreased
resist ance t o passive mot ion. This hypot onia may be t he result of w eakness
prevent ing volunt ary act ivit y[344] .
The act ions of agonist muscles, w hich have t he same or similar mechanical
eff ect s on a joint , and ant agonist muscles, w hich have t he opposit e eff ect ,
should be considered in t est ing t he st rengt h of a part icular muscle. The act ion of
a pow erf ul agonist may conceal w eakness in a smaller muscle (e. g. , t he
pect oralis may compensat e f or subscapular muscle w eakness). Also, cert ain
muscles may appear w eak because t heir act ion requires t he support of t he
paralyzed muscles (e. g. , f inger abduct ion by t he dorsal int erossei may seem
w eak w hen a radial nerve palsy prevent s f ixat ion of t he w rist ). A nerve of t en
supplies several muscles w it h a similar act ion, and a lesion of t hat nerve result s
in w eakness of t he muscle group.
Disturbances of Muscle Stretch Reflexes

As a consequence of sensorimot or loss, t he muscle st ret ch ref lex subserved by
each damaged nerve is decreased or absent .
Vasomotor, Sudomotor, and Trophic Disturbances

The skin subserved by t he aff ect ed nerve may become t hin and scaly. The nails
may become curved, w it h ret ardat ion of nail and hair grow t h in t he aff ect ed
area. The aff ect ed area of t he skin may become dry and inelast ic and may cease
t o sw eat . Because t he analgesic cut aneous area is liable t o injury, ulcers may
develop.
Alt hough ancillary procedures (e. g. , elect romyography and nerve st imulat ion
st udies, muscle and nerve biopsy, sw eat t est s) great ly aid in t opographic
diagnosis, t he f ollow ing discussion st resses only t he bedside diagnosis and
localizat ion of individual peripheral nerve abnormalit ies.
M ononeuropathy M ultiplex
Mononeuropat hy mult iplex (mult if ocal mononeuropat hy) ref ers t o t he involvement
of several isolat ed nerves. The nerves involved are of t en w idely separat ed (e. g. ,
right median and lef t f emoral nerve). These mult iple neuropat hies result in
sensory and mot or dist urbances t hat are conf ined t o t he aff ect ed individual
nerves. Mononeuropat hy mult iplex is usually due t o a disseminat ed vasculit is t hat
aff ect s individual nerves (e. g. , vasculopat hy in diabet es mellit us or polyart erit is
nodosa).
Polyneuropathy
I n polyneuropat hy, t he essent ial f eat ure is t he impairment of f unct ion of many
peripheral nerves simult aneously, result ing in a symmet ric, usually dist al, loss of
f unct ion. The charact erist ic f eat ures include muscle w eakness w it h or w it hout
at rophy, sensory dist urbances, aut onomic and t rophic changes, and hyporef lexia
or aref lexia. I n general, t he legs are aff ect ed bef ore t he arms. Polyneuropat hy
may be caused by diff erent processes and may be mainly sensory (e. g. ,
amyloidosis, paraneoplast ic, leprosy), mot or (e. g. , G uillain-Barré syndrome,
porphyria, lead int oxicat ion), or bot h sensory and mot or.
The loss of sensat ion in peripheral polyneuropat hies may involve all modalit ies of
sensat ion, but because nerve f ibers of a specif ic caliber may be pref erent ially
involved in t he pat hologic process, sensory impairment may be rest rict ed t o a
cert ain f orm of sensat ion (dissociat ion of sensory loss). Pref erent ial loss of pain
and t emperat ure percept ion may be seen in t ype I heredit ary sensory
neuropat hy, amyloid neuropat hy, Tangier disease, and in some cases of diabet ic
neuropat hy. Wit h t hese neuropat hies, smaller-diamet er nerve f ibers conveying
pain and t emperat ure sensat ion are pref erent ially involved. A select ive loss of
t ouch pressure, t w o-point discriminat ion, and joint posit ion sense (conveyed by
larger myelinat ed f ibers) w it h spared pain and t emperat ure sensibilit y may occur
w it h Friedreich's at axia, vit amin B12 def iciency, and t he syndrome G uillain-Barré
syndrome.
The pat t ern of sensory and mot or def icit s in many polyneuropat hies (e. g. ,
diabet ic polyneuropat hy) develops according t o axonal lengt h, w it h sensory
changes init ially occurring at sit es most dist al f rom dorsal root ganglia
cells[ 278] . When t he sensory abnormalit y in t he limbs ext ends proximally t o 35 t o
50 cm f rom t he dorsal root ganglia, t here is also a region of sensory loss over
t he ant erior t orso in accordance w it h t he lengt h of axons t raversing t he body
w all. This sensory abnormalit y is w ider in t he low er abdomen and t ends t o be
narrow er in t he t horacic region because of t he longer, more oblique course of
t he sensory f ibers t o t he low er abdomen and t he short er course of t he nerves
t raveling along t he ribs. When nerves <20 t o 24 cm in lengt h become involved, a
“beanie cap” of sensory change over t he scalp vert ex occurs ow ing t o t he dist al
involvement of t he opht halmic branches of t he t rigeminal nerves. I n ext reme
sensory neuropat hies, only t he short est (<12 cm) nerve f ibers are spared, so
t hat t here is sensory loss over t he ent ire body except f or a band of int act
sensat ion over t he post erior midline f rom t he occiput t o t he sacral region[278] .
The axonal lengt h principle may also be applied t o mot or neuropat hies w here
of t en t he int rinsic f oot muscles are init ially aff ect ed, f ollow ed by t he peroneal
innervat ed muscles, and t hen by gast rocnemius-soleus involvement [278] . The
ant erior t ibial compart ment is aff ect ed bef ore t he post erior t ibial compart ment
because t he f ormer's nerve supply is longer t han t he lat t er by more t han 10 cm.
When all muscle groups below t he knee are aff ect ed, int rinsic hand muscle
involvement w ill develop. Pat ient s w it h peripheral mot or neuropat hies of t en have
great er mot or w eakness of ankle dorsif lexors t han f oot plant ar f lexors on a
biomechanical as w ell as a physiologic basis[43] . I n f act in pat ient s w it h great er
w eakness of ankle plant ar f lexors t han dorsif lexors, w ho are able t o w alk on
t heir heels but not on t heir t oes, int raspinal disease (e. g. , conus-cauda equina
t umor, spinal muscular at rophy, spinal st enosis, carcinomat ous meningit is) rat her
t han peripheral polyneuropat hy should be suspect ed[43] .
I n some neuropat hies (e. g. , Tangier disease), t he short axons are pref erent ially
involved, and hence t he sensory loss st art s proximally and progresses dist ally,
somet imes t o t he point w here t he ent ire body, except f or t he hands and regions
below t he knees, show s sensory impairment . Porphyric neuropat hy may also

st art proximally, w it h paresis aff ect ing t he proximal arms, proximal legs, dist al
arms, and t hen dist al legs (in t hat order). The muscle st ret ch ref lexes in
porphyria may be complet ely lost except f or preserved ankle jerks, and t he
sensory loss may involve only t he t runk, f ace, and proximal arms and t highs.
I n some ot her neuropat hies, t he init ial involvement and subsequent progression
of clinical def icit s may not be det ermined by t he axonal lengt h. For example, in
lepromat ous leprosy neuropat hy, sensory loss occurs init ially over t he areas of
t he body having cooler surf ace t emperat ures (e. g. , t he t ip of t he nose, t he malar
areas of t he cheeks)[ 279] because t he prolif erat ion of Mycobacteri um l eprae is
great er in cooler t issues.
Lesions of Individual Nerves

Alt hough peripheral nerves originat e in plexuses (discussed in Chapt er 3), it is
easier t o underst and t he course of peripheral nerves bef ore review ing t he
anat omy of t he plexuses, t han t o underst and t he sympt omat ology of plexus
lesions w it hout t he benef it of know ing peripheral innervat ion. For t his reason, t he
aut hors have chosen t o place t his chapt er f irst . Diagrams of t he origin of each
nerve in t he plexi can be f ound in Chapt er 3.
Nerve f ibers do not randomly int ert w ine as t hey progress dist ally in nerve
bundles. Evidence indicat es t hat specif ic axons remain grouped t oget her,
part icularly t hrough t heir dist al course, as t hey t ravel t ow ard t heir
dest inat ion[ 325] . Adjacent muscles and, similarly, adjacent sensory dermat omes
are innervat ed by nerve f ascicles t hat remain t oget her w it hin t he nerve bundle.
Theref ore, ulnar neuropat hies clinically “localized” t o t he w rist may act ually be
occurring at t he elbow because of t he pref erent ial involvement of cert ain
f ascicles, w hereas a proximal sciat ic neuropat hy somet imes masquerades as a
peroneal neuropat hy at t he knee. These anat omic arrangement s must alw ays be
t aken int o account w hen localizing pat hologic processes[325] .
Dorsal Scapular Nerve (C4–C5)

Anatomy
The dorsal scapular nerve (a purely mot or nerve) arises mainly f rom t he C5
spinal nerve w it hin t he subst ance of t he scalenus medius muscle. The nerve
courses dow nw ard behind t he brachial plexus deep t o t he levat or scapulae
muscle (w hich it supplies) and t erminat es by piercing t he deep surf aces of t he
rhomboids (major and minor). The rhomboids normally elevat e and adduct t he
medial border of t he scapula (t hey are ant agonist s of t he serrat us ant erior) and,
along w it h t he levat or scapulae, rot at e t he scapula so t hat t he inf erior angle
moves medially. The rhomboids are t est ed by having t he pat ient press his or her
elbow backw ard against resist ance w hile t he hand is on t he hip[339] .
Nerve Lesions
Because t he dorsal scapular nerve derives f rom t he proximal plexus, aff ect ion of
t his nerve in an upper brachial plexopat hy suggest s a proximal lesion. The nerve
may also be ent rapped w it hin t he subst ance of t he scalenus medius muscle.
I solat ed lesions of t his nerve may occur in body builders[219] . A dorsal scapular
nerve lesion result s in t he lat eral displacement of t he vert ebral border of t he
scapula, w hich is rot at ed, w it h t he inf erior angle displaced lat erally. Rhomboid
at rophy is concealed by t he overlying t rapezius muscle. Rhomboid paresis is
evident if t he elbow can be pressed back only w eakly against resist ance
(keeping t he hand on t he hip). Weakness is also evident w hen t he pat ient
at t empt s t o push t he palm backw ard against resist ance w it h t he arm f olded
behind t he back.
Subclavian Nerve (C5–C6)

This purely mot or nerve emerges f rom t he upper t runk of t he brachial plexus and
descends in t he post erior cervical t riangle t o innervat e t he subclavian muscle.
This muscle depresses and medially draw s t he lat eral end of t he clavicle.
Lesions of t he subclavian nerve cause no import ant clinical dist urbances.
Long Thoracic Nerve (C5–C7)

Anatomy
This purely mot or nerve (Fig. 2-1) arises f rom t he C5–C7 root s short ly af t er t hey
emerge f rom t he int ervert ebral f oramina. Af t er passing t hrough t he scalenus
muscle, t he t w o upper root s are joined by a cont ribut ion f rom t he C7 root . The
nerve runs post erior t o t he brachial plexus and inf eriorly behind t he clavicle and
t hen crosses t he out er border of t he f irst rib t o reach t he serrat us ant erior
muscle. The nerve f urt her descends along t he lat eral t horacic w all, sending
individual f ilament s t o t he muscle slips of t he serrat us.
The serrat us ant erior muscle f ixes and st abilizes t he scapula against t he chest
w all and is t est ed by observing f or scapular w inging (t he vert ebral border of t he
scapula st ands aw ay f rom t he
t horax, f orming a “w ing”) w hile t he pat ient pushes ext ended arms against a f ixed
object (e. g. , a w all)[ 339] .
FI G URE 2-1 The long t horacic nerve.
Nerve Lesions
The long t horacic nerve lies superf icially in t he supraclavicular region w here it is
subject t o t rauma [108] . Theref ore, it is injured most f requent ly as a result of
pressure on t he shoulder (e. g. , sudden t rauma or carrying heavy object s on t he
shoulder—rucksack paral ysi s)[ 246] . Direct t rauma t o t he shoulder or t he lat eral
t horacic w all w hile playing f oot ball, or during a f all, or an aut o accident may
compress t he nerve. Chiropract ic manipulat ion of t he cervical spine may also
cause nerve injury[238] . Work-relat ed or at hlet ic act ivit ies, especially t hose
involving repet it ive st ressf ul movement s of t he shoulder or t hose in w hich t he
arm is in an out st ret ched overhead posit ion, may cause st ret ch or t ract ion
injury[ 288] . The overhead arm posit ioning may be a f act or in t he development of
isolat ed long t horacic neuropat hy during surgery w it h general anest hesia[165] . I n
a review of 197 cases of long t horacic neuropat hy, 32 cases w ere iat rogenic
ow ing t o local invasive procedures such as f irst rib resect ions, mast ect omies
w it h axillary node dissect ion, t horacot omy, scalenect omies, inf raclavicular plexus
anest hesia, and chest t ube insert ion[165] . The nerve may be injured in up t o 10%
of pat ient s undergoing radical mast ect omies and in approximat ely 1% of pat ient s
undergoing simple mast ect omies[90] . I solat ed long t horacic nerve palsy may also
occur as a manif est at ion of neuralgic amyot rophy (Parsonage-Turner syndrome)
[ 95] or, rarely, af t er radiat ion t herapy f or breast cancer[258] . Also, f amilial long
t horacic nerve palsy may be a major manif est at ion of f amilial brachial plexus
neuropat hy[ 248] , and painf ul long t horacic neuropat hy has been described as t he
sole manif est at ion of Lyme disease [222] .
Nerve paralysis usually causes no def ormit y of t he scapula w hen t he arm is at
rest . I f , how ever, t he pat ient is asked t o push t he arm f orw ard against
resist ance or hold t he arms up in f ront of t he body, t he scapula becomes w inged
(wi nged scapul a or scapul a al ata), especially in it s low er t w o-t hird region. The
pat ient of t en complains of w eakness of t he shoulder and f at igue on raising t he
arm above t he head. Wit h injuries caused by excessive nerve st ret ch during
physical act ivit ies, t he sharp pain in t he shoulder may radiat e t o t he neck and
upper arm.
Suprascapular Nerve (C5–C6)

Anatomy
This purely mot or nerve (Fig. 2-2) is a branch of t he upper t runk of t he brachial
plexus. The nerve passes dow nw ard beneat h t he t rapezius t o t he upper border
of t he scapula, w here it passes t hrough t he suprascapular not ch. This not ch is
bridged by t he superior t ransverse scapular ligament , f orming an osseof ibrous
f oramen t hrough w hich t he nerve passes t o ent er t he supraspinous area beneat h
t he supraspinat us muscle. The nerve gives off branches t o t he supraspinat us and
t o t he capsule of t he shoulder joint and t hen courses around t he f ree lat eral
border of t he spine of t he scapula t o supply t he inf raspinat us muscle. Alt hough
t he suprascapular nerve is said t o have no cut aneous branches, rare cases have
provided evidence f or a cut aneous branch of t he suprascapular nerve, as
described in cadaveric st udies[131] .
The supraspinat us muscle normally abduct s t he humerus (mainly t he f irst 15
degrees of abduct ion), w hereas t he inf raspinat us muscle is mainly an ext ernal
rot at or of t he upper arm.
Nerve Lesions
The nerve may be injured in proximal upper brachial plexopat hies and is also
subject t o damage in t he supraclavicular region, especially w it h
acut e f orcef ul depression of t he shoulder and it s dislocat ion. Fract ures of t he

suprascapular not ch or excessive callus f ormat ion af t er scapular f ract ure may
compress t he nerve. The nerve may also be injured af t er repair of rot at or cuff
t ears[ 370] . Repet it ive f orced cross-body adduct ions of t he arm or repet it ive
mot ions involving t he scapulot horacic and shoulder joint s may also injure t he
nerve. Suprascapular nerve injury has even been report ed af t er driving f or 2
hours speaking on a mobile t elephone w it h t he phone cradled bet w een t he ear
and shoulder, probably by t he nerve being compressed by t he hard edge of t he
phone (mobi l e tel ephone user's shoul der droop)[ 141] . O t her et iologies of nerve
injury include occupat ional overuse, sport s-relat ed injuries, direct nerve t rauma,
and ganglion cyst s[172] .
FI G URE 2-2 The suprascapular nerve.
Ent rapment lesions (e. g. , ganglia) may occur in t he suprascapular f oramen [13,
55, 189, 207, 264] . This ent rapment causes shoulder pain, w hich is aggravat ed
by shoulder girdle movement s, w eakness, and event ual at rophy in t he t w o spinat i
muscles. The pain is deep, locat ed along t he superior border of t he scapula
of t en ext ending t ow ard t he shoulder joint , occasionally radiat ing int o t he arm,
and is made w orse by movement s t hat adduct t he scapula or rot at e t he head
aw ay f rom t he involved shoulder. Supraspinat us paresis result s in w eakness of
arm abduct ion, w hereas inf raspinat us paresis result s in impaired ext ernal
rot at ions at t he shoulder joint . Suprascapular involvement may also occur w it h
neuralgic amyot rophy[95] .
Harbaugh et al. described a pat ient w it h suprascapular nerve ent rapment at t he
suprascapular not ch present ing w it h right shoulder pain and at rophy w it h
w eakness of t he right supra- and inf raspinat us muscles[131] . The pat ient w as
not ed t o also have an area of numbness involving t he right upper lat eral
shoulder. Alt hough t he suprascapular nerve is said t o have no cut aneous
branches, t his case provides evidence f or a cut aneous branch of t he
suprascapular nerve[131] .
The branch of t he inf raspinat us muscle may be damaged in isolat ion by t he
ent rapment of t he suprascapular nerve at t he spinoglenoid not ch by a
hypert rophied inf erior t ransverse scapular ligament or a ganglion [7, 175, 189] .
This result s in shoulder pain, w hich is elicit ed by t he ext ernal rot at ion of t he
shoulder joint , associat ed w it h w eakness and w ast ing of t he inf raspinat us.
Lesions at t he suprascapular not ch may also cause isolat ed inf raspinat us
w eakness by involving only t he port ion of t he nerve dest ined t o innervat e t he
inf raspinat us muscle [37, 175, 317] . A lesion of t he suprascapular nerve at t he
glenoid not ch, causing isolat ed inf raspinat us paresis and at rophy, may occur as
a prof essional hazard in volleyball players[221] . I solat ed inf raspinat us paresis
may also result f rom a nerve injury in body builders[40, 219] .
Subscapular Nerves (C5–C7)

Anatomy
These purely mot or nerves arise as branches of t he post erior cord of t he
brachial plexus. The upper subscapular nerves supply t he subscapularis,
w hereas t he low er subscapular nerves supply t he t eres major.
Nerve Lesions
Subscapular nerve palsies usually occur w it h post erior cord brachial plexus
lesions. The arm is somew hat ext ernally rot at ed, w it h some paresis of
int ernal rot at ion, alt hough t he lat issimus dorsi and pect oralis major muscles are
usually able t o compensat e w ell f or t his paresis. The pat ient may complain of
diff icult y in scrat ching t he low er back.
Thoracodorsal Nerve (C6–C8)

Anatomy
This purely mot or nerve, also know n as t he nerve to the l ati ssi mus dorsi, is a
branch of t he post erior cord of t he brachial plexus and usually emerges f rom t he
plexus in close associat ion w it h t he subscapular nerves. The nerve runs along
t he post erior axillary w all t o reach and innervat e t he deep surf ace of t he
lat issimus dorsi muscle. This muscle (along w it h t he t eres major) adduct s and
int ernally rot at es t he arm and depresses t he raised arm. I t is best t est ed by
having t he pat ient adduct t he horizont ally raised upper arm against resist ance or
by palpat ing t he muscle bellies w hen t he pat ient coughs[339] .
Nerve Lesions
Lesions of t his nerve usually occur w it h damage t o t he post erior cord or proximal
part s of t he brachial plexus. Nerve lesions cause lit t le def ormit y or at rophy, but
proximal arm adduct ion is compromised. A combined movement comprising
ext ension, adduct ion, and int ernal rot at ion, in w hich t he dorsum of t he hand is
placed on t he opposit e but t ock, readily reveals lat issimus paresis. I solat ed
t horacodorsal nerve injury has been described in body builders[40, 219] .
Anterior Thoracic Nerves (C5–T1)
Anatomy
The ant erior t horacic nerves, purely mot or nerves, (also called t he pectoral
nerves) are divided int o t he lat eral ant erior t horacic nerve (C5–C7), a branch
f rom t he ant erior divisions of t he upper and middle t runks of t he brachial plexus,
and t he medial ant erior t horacic nerve (C8–T1), a branch of t he proximal sect ion
of t he medial cord of t he plexus. Af t er t hese nerves descend post eriorly t o t he
clavicle, t he lat eral nerve supplies t he clavicular and upper st ernocost al port ions
of t he pect oralis major, and t he medial division supplies t he low er st ernocost al
port ion of t his muscle and t he pect oralis minor.
The pect oralis major is an adduct or and medial rot at or of t he humerus. I t is
t est ed by having t he pat ient hold t he arm in f ront of t he body. The t w o port ions
can be seen and palpat ed w hen t he pat ient resist s at t empt s by t he examiner t o
f orce t he arm lat erally[339] .
Nerve Lesions
Lesions of t hese nerves are of relat ively lit t le localizing import ance except in
corroborat ing brachial plexus damage. Adduct ion and medial rot at ion of t he
upper arm are w eak, and t he pat ient not ices diff icult y in using t he arm in
climbing. I solat ed injury t o t he lat eral ant erior t horacic nerve as t he result of a
seat -belt injury may result in at rophy of t he clavicular head of t he pect oralis
major[ 199] . Weight lif t ers may develop medial ant erior t horacic nerve injury in
isolat ion or in associat ion w it h t horacodorsal nerve injury[40, 219] . Bilat eral
medial ant erior t horacic neuropat hies in a w eight lif t er w ere t hought t o be due t o
concomit ant pect oralis minor hypert rophy causing int ramuscular ent rapment of
t he nerves[272] .
G ardet t o et al. report ed t w o cases of isolat ed damage t o a muscle branch of t he
lat eral pect oral nerve[110] . I n bot h t hese pat ient s, f ocal muscle at rophy
developed gradually af t er t he init iat ion of t raining schedules t o increase t he
cross sect ion of t he major pect oral muscle. The aut hors t heref ore assumed t hat
compression injury t o t he nerve by repet it ive muscle cont ract ions may have been
of pat hogenic relevance. Anat omical st udies of t his region show ed t hat t he nerve
branches of t he lat eral pect oral nerve, having t o pierce t hrough a connect ive
t issue sept um t hat is t hicker by a f ew millimet ers, may be subject ed t o an
addit ional risk of compression[110] .
Axillary Nerve (C5–C6)

Anatomy
The axillary (circumf lex) nerve (Fig. 2-3), a mixed nerve, arises as one of t he
t erminal branches of t he post erior cord of t he brachial plexus f rom spinal
segment s C5 and C6. I t lies f irst on t he lat eral side of t he radial nerve, t hen
courses lat erally and backw ard t o pass just below t he shoulder joint . I t t hen
goes t hrough t he quadri l ateral space, an anat omical compart ment bounded
inf eriorly by t he t eres major muscle, medially by t he long head of t he t riceps
muscle, lat erally by t he surgical neck of t he humerus, and superiorly by t he t eres
minor muscle and subscapularis muscle. The nerve descends on t he
subscapularis muscle behind t he axillary art ery and t hen w inds around t he
surgical head of t he humerus, accompanied by t he post erior circumf lex humeral
art ery. I t passes deep int o t he delt oid and t eres minor muscles, supplying bot h.
I t sends sensory branches t o t he capsule of t he shoulder joint (arti cul ar branch)
and t o t he skin of t he upper lat eral aspect of t he arm superf icial t o t he delt oid
muscle (l ateral cutaneous nerve of the arm).
FI G URE 2-3 The axillary nerve.
The t eres minor muscle is a lat eral rot at or of t he shoulder joint . The cent ral part
of t he delt oid muscle is t est ed by having t he pat ient abduct t he upper arm
against resist ance (15–90 degrees), t he ant erior part by elevat ing t he arm
f orw ard against resist ance (up t o 90 degrees), and t he post erior part by having
t he pat ient ret ract t he abduct ed upper arm against resist ance.
Nerve Lesions
Lesions of t he post erior cord of t he brachial plexus aff ect t his nerve as w ell as
t he radial nerve (e. g. , crut ch paralysis). Trauma is t he most common cause of
axillary neuropat hy. The axillary nerve is t hought t o be most vulnerable t o
t ract ion injury of t he brachial plexus because it is t et hered t o t he delt oid muscle
very close t o t he shoulder [35, 142, 241] . The nerve is most of t en injured as it
w inds around t he lat eral aspect of t he humerus in a relat ively exposed posit ion
(e. g. , w it h f ract ure and dislocat ion of t he humerus), w hen t he shoulder joint is
dislocat ed or w hen t he scapula is f ract ured[15] . The axillary nerve may also be
injured during reduct ion of a shoulder dislocat ion[359] . Axillary neuropat hy may
occur secondary t o int ramuscular inject ion high in t he post erior aspect of t he
shoulder[ 156] , af t er sleeping in a prone posit ion w it h t he arm raised above t he
head, f ollow ing laparot omy (at t ribut ed t o suspending t he f orearm f rom t he
anest hesia screen t o gain bet t er abdominal exposure), w it h neuralgic
amyot rophy[ 95] or by direct nerve injury in at hlet es [241, 244] . The nerve may
be injured direct ly or ent rapped by a f ibrous band in t he quadrilat eral space[106,
209] . O t her et iologies of axillary injury in t he quadrilat eral space include t rauma
in at hlet es (especially volleyball players, baseball pit chers, and t ennis players),
t he use of prost het ic devices f or t he upper arm using a “f igure of eight ” t ype of
suspension, and hypert rophy of cont iguous muscles[241] . As t he post erior
humeral circumf lex art ery also runs in t he quadrilat eral space, subclavian
angiography in t he quadrilat eral syndrome may reveal occlusion of t his vessel
w hen t he arm is abduct ed and ext ernally rot at ed[54] .
Nerve injuries usually cause a sensorimot or nerve palsy, but a purely mot or
nerve palsy is possible w it h nerve lesions at t he humeral head. A purely sensory
loss w it h no mot or def icit s is also possible[41] . For example, isolat ed damage t o
t he sensory branch af t er art hroscopic surgery has been described[292] . I n nerve
lesions, t he delt oid muscle becomes at rophic, causing a f lat t ening or concavit y
of t he shoulder cont our. Teres minor paresis is usually not demonst rable on
clinical examinat ion because ot her muscles can perf orm it s f unct ions. Delt oid
paralysis result s in diff icult y in abduct ing t he arm, but ot her muscles of t he
shoulder girdle can compensat e t his f unct ion. An axillary cut aneous sensory
def ect is locat ed on t he out er aspect of t he upper arm and is maximal on t he
pat ch of skin above t he delt oid at t achment .
Musculocutaneous Nerve (C5–C7)

Anatomy
The musculocut aneous nerve, a mixed nerve (Fig. 2-4) arises f rom t he lat eral
cord of t he brachial plexus and proceeds obliquely dow nw ard bet w een t he
axillary art ery and t he median nerve. The nerve pierces t he coracobrachialis
muscle and descends f urt her bet w een t he biceps and brachialis muscles (it
supplies all t hese t hree muscles). I t may rarely innervat e t he pronat or t eres
muscle (most of t en a median-innervat ed muscle). The nerve t hen cont inues
dist ally as t he lat eral cut aneous nerve of t he f orearm af t er it pierces t he deep
f ascia over t he ant erior elbow. The coracobrachialis muscle is a f orw ard elevat or
of t he arm, t he brachialis (w hich occasionally also receives innervat ion f rom t he
radial nerve) is an elbow f lexor, and t he biceps is an elbow f lexor and f orearm
supinat or (especially w hen t he elbow is f lexed at 90 degrees). The biceps is
t est ed by having t he pat ient f lex t he supinat ed arm against resist ance[339] . The
biceps ref lex is subserved by t he musculocut aneous nerve.
The aut onomous zone of t he lat eral cut aneous nerve of t he f orearm (a narrow
band along t he radial f orearm) show s sensory loss w it h musculocut aneous nerve
lesions. This zone of cut aneous sensory loss may ext end f rom t he elbow t o t he
w rist and cover t he ent ire lat eral f orearm f rom t he dorsal t o t he vent ral midline.
FI G URE 2-4 The musculocut aneous nerve.
Nerve Lesions
Nerve damage may result f rom lesions of t he lat eral cord of t he brachial plexus.
Proximal humeral lesions (e. g. , f ract ures, ost eochondroma) or shoulder
dislocat ions may injure or compress t he nerve [158] . Because t he nerve is deep
and is prot ect ed bet w een t he ent ry sit e int o t he coracobrachialis and t he elbow,
lesions are relat ively uncommon here. A predominant ly mot or musculocut aneous
neuropat hy may develop af t er st renuous exercise of t he upper ext remit y,
probably due t o nerve ent rapment or st ret ch of t he nerve w here it passes
t hrough t he coracobrachialis muscle in t he upper arm[203] . Mot or and sensory
neuropat hy may develop in t his locat ion af t er w eight lif t ing, st renuous physical
act ivit y, row ing, f oot ball t hrow ing, general anest hesia, or sleep [44, 147, 173,
285] and has been described t o occur w it h repet it ive carrying of a heavy, rolled
object by t he shoulder w it h t he object held in place by t he arm curled around t he
object (carpet carri er's pal sy)[ 285] . I solat ed biceps w eakness may occur w it h
dist al mot or nerve injury[40] . A purely sensory syndrome may result w hen t he
lat eral cut aneous nerve of t he f orearm is damaged in t he cubit al f ossa or
f orearm. This sensory branch may be injured by compression[232] ,
venipunct ure[ 36] , or cut dow n procedures because it lies direct ly under t he
median cubit al vein in t he cent er of t he cubit al f ossa. Typically, pat ient s not ice
pain in t he proximal f orearm, of t en aggravat ed by elbow ext ension,
and parest hesias along t he radial aspect of t he f orearm. A pure sensory

neuropat hy has also been observed in w indsurf ers w ho f lex t he upper ext remit y
slight ly at t he elbow w it h t he hand gripped over t he boom[150] ; t his has also
been observed w it h nerve compression f rom a handbag (handbag paresthesi a)
[ 129] and w it h nerve compression by t he biceps aponeurosis[75] .
Wit h lesions of t he musculocut aneous nerve, at rophy of t he biceps and brachialis
result s in w ast ing of t he vent ral aspect of t he upper arm. Loss of
coracobrachialis f unct ion is diff icult t o det ect clinically. Wit h biceps w eakness,
f lexion of t he elbow is w eak (especially w hen t he f orearm is supine), and t he
biceps ref lex is lost .
FI G URE 2-5 The median nerve.
Median Nerve (C6–T1)

Anatomy
The mixed median nerve (Fig. 2-5) is f ormed in t he axilla by t he joining of t he
lat eral cord of t he brachial plexus (spinal segment s C6–C7) w it h t he medial cord
(spinal segment s C8–T1). The nerve t hen descends dow n t he medial side of t he
arm in close associat ion w it h t he brachial art ery t o t he cubit al f ossa. From t here,
t he median nerve ent ers t he f orearm bet w een t he t w o heads of t he pronat or
t eres muscle and gives off t he anteri or i nterosseous nerve, af t er w hich it dips
under t he sublimis bridge. I t t hen courses deep t o t he f lexor ret inaculum at t he
w rist (carpal tunnel) t o reach
t he hand. At a variable dist ance above t he f lexor ret inaculum, t he median nerve
provides a pal mar cutaneous branch, w hich crosses t he f lexor ret inaculum eit her
subcut aneously or t hrough t he superf icial ligament f ibers t o supply t he skin over
t he t henar eminence and proximal palm on t he radial aspect of t he hand. The
median nerve passes t hrough t he carpal t unnel accompanied by t he f lexor
t endons of t he digit s and emerges t o divide int o it s t erminal branches. These
t erminal branches include branches t o t he t henar muscles and t he pal mar di gi tal
nerves, w hich innervat e t he skin of t he palmar aspect of t he t humb, t he second,
t hird, and half of t he f ourt h f inger; t he palm overlying t he corresponding
met acarpophalangeal joint s; and t he post erior middle and dist al phalanges of t he
second, t hird, and half of t he f ourt h f inger.
The median nerve gives off no muscular branches unt il it reaches t he elbow. As it
passes bet w een t he heads of t he pronat or t eres muscle, it supplies t he f ollow ing
muscles:
1. Pronator teres (C6–C7), a f orearm pronat or. I t is t est ed by having t he

pat ient pronat e t he f orearm against resist ance. This muscle may rarely be
innervat ed by t he musculocut aneous nerve.
2. Fl exor carpi radi al i s (C6–C7), a radial f lexor of t he hand. This is t est ed by
having t he pat ient f lex and abduct t he hand at t he w rist against resist ance.
3. Pal mari s l ongus (C7–T1), a f lexor of t he w rist .
4. Fl exor di gi torum superf i ci al i s (C7–T1), a f lexor of t he middle phalanges of
t he second, t hird, f ourt h, and f if t h f ingers. I t is t est ed by having t he pat ient
f lex t he f inger at t he int erphalangeal joint against resist ance, w it h t he
proximal phalanx f ixed.
Af t er it passes bet w een t he t w o heads of t he pronat or t eres, t he median nerve

gives off t he purely mot or anteri or i nterosseus nerve, w hich innervat es t he
f ollow ing muscles:
1. Fl exor pol l i ci s l ongus (C7–C8), a f lexor of t he t erminal phalanx of t he t humb,

it is t est ed by having t he pat ient f lex t he dist al phalanx of t he t humb against
resist ance, w hile t he proximal phalanx is f ixed.
2. Fl exor di gi torum prof undus I and II (C7–C8), a f lexor of t he t erminal
phalanges of t he second and t hird f ingers. I t is t est ed by having t he pat ient
f lex t he dist al phalanx of t he second and t hird f ingers against resist ance,
w it h t he middle phalanx f ixed.
3. Pronator quadratus (C7–C8), a f orearm pronat or.
At t he dist al end of t he carpal t unnel, t he median nerve divides int o it s t erminal

branches. The mot or branches innervat e t he f irst and second lumbricals and t he
t henar muscles, w hich include t he f ollow ing:
1. Abductor pol l i ci s brevi s (C8–T1), an abduct or of t he met acarpal of t he

t humb. I t is t est ed by having t he pat ient abduct t he t humb at right angles t o
t he palm against resist ance.
2. O pponens pol l i ci s (C8–T1), a muscle t hat brings t he met acarpal of t he
t humb int o opposit ion. I t is t est ed by having t he pat ient t ouch t he base of t he
lit t le f inger w it h t he t humb against resist ance.
3. Superf i ci al head of the f l exor pol l i ci s brevi s (C8–T1), a f lexor of t he
proximal phalanx of t he t humb.
4. Lumbri cal s I and II (C8–T1), f lexors of t he proximal and ext ensors of t he t w o
dist al phalanges of t he second and t hird f ingers. They are t est ed by having
t he pat ient ext end t he f inger at t he proximal int erphalangeal joint against
resist ance, w it h t he met acarpophalangeal joint f ixed and hyperext ended.
The f inger f lexor ref lex (C8–T1) is in part innervat ed by t he median nerve.
I t is import ant t o be aw are of pot ent ial variat ions in t he innervat ion of t he
int rinsic hand muscles. Anomalous communicat ions in t he hand are somet imes
ref erred t o as Ri che-Canni eu anastomoses[ 127] and are t hought t o involve
communicat ions bet w een t he mot or branch of t he median nerve and t he deep
ulnar nerve branch in t he radial aspect of t he hand. For example, t he adduct or
pollicis and f irst dorsal int erosseous muscles may be exclusively supplied by t he
median nerve (in 2% and 1% of individuals, respect ively) and are t heref ore
involved in median nerve lesions and spared in ulnar lesions. Also, t he abduct or
pollicis brevis and t he f lexor pollicis brevis may be exclusively supplied by t he
ulnar nerve in 2% of individuals.
Nerve Lesions
Lesions in the Axilla and Upper Arm
Median neuropat hies in t he axilla are of t en associat ed w it h damage t o t he ulnar
and radial nerves (tri ad neuropathy) or brachial plexus. Et iologies include crut ch
compression, sleep paralysis, penet rat ing t rauma, shoulder dislocat ion, vascular
malf ormat ions, and sheat h hemorrhage [273] . I n t he upper arm, t he nerve may
be damaged by penet rat ing t rauma, humerus f ract ures, sleep paralysis, and
art eriovenous f ist ulas [345] . The median nerve may be compressed in t he upper
arm by an anomalous course of t he brachialis
muscle[ 223] . Median lesions in t he axilla or upper arm result in paresis or

paralysis of all t he muscles innervat ed by t he median nerve, w it h a sensory loss
in t he dist ribut ion of bot h t he palmar cut aneous and palmar digit al branches.
There is at rophy of t he t henar eminence, aff ect ing especially t he abduct or
pollicis brevis and t he opponens pollicis. Because of t his at rophy, w it h recession
of t he met acarpal bones of t he t humb t o t he plane of t he ot her met acarpal
bones, t he hand t akes on an abnormal appearance called si mi an hand or ape
hand. This appearance result s f rom t he unopposed act ion of t he ext ensor pollicis
longus (radial nerve) and t he adduct or pollicis (ulnar nerve). Because t he second
f inger cannot be f lexed and t he t hird f inger can be f lexed only part ially, w hen t he
person at t empt s t o make a f ist , t hese f ingers remain ext ended. The hand t hen
t akes on t he appearance of t hat of a clergyman off ering benedict ion (benedi cti on
hand). Because all t he median muscles are aff ect ed, t here are pareses of
f orearm pronat ion, radial w rist f lexion, dist al f lexion of t he t humb, palmar
abduct ion, and opposit ion of t he t humb and f lexion of t he second and, t o a lesser
ext ent , t he t hird f ingers.
Lesions at the Elbow

Median nerve compression at t he elbow may be due t o t umors and ot her
masses, St rut hers' ligament or ot her anomalous ligament s, supracondylar spurs,
ent rapment w it hin t he t w o heads of t he pronat or t eres muscle, a large brachialis
muscle, t he overlying bicipit al aponeurosis, venous varix, and bone or ligament
injuries (e. g. , elbow f ract ure or dislocat ion) [70, 73, 371] . Vascular causes
include cat het erizat ion, t hrombosis, anomalies such as a persist ent median
art ery, an anomalously enlarged ulnar art ery, or a f alse aneurysm of t he brachial
art ery [130, 132, 256, 270, 371] . Mot or and sensory signs and sympt oms are as
described earlier in Lesions in t he Axilla and Upper Arm but elbow lesions may
also cause an ant erior int erosseous or pseudoant erior int erosseous syndrome
(see subsequent t ext ).
Lesions at the Ligament of Struthers

I n approximat ely 1% of t he populat ion, an anomalous spur of t he bone occurs 3
t o 5 cm above t he medial epicondyle on t he ant eromedial humerus. A f ibrous
t unnel may be f ormed by a ligament (l i gament of Struthers) t hat connect s t his
spur t o t he medial epicondyle. The median nerve may be compressed here by
t his ligament , causing mot or and sensory signs and sympt oms as described
earlier in Lesions in t he Axilla and Upper Arm[18, 38] . The ligament may also
compress t he brachial art ery or, rarely, t he ulnar nerve[218] .
The Pronator Syndrome

The median nerve may be ent rapped or const rict ed w here it passes bet w een t he
t w o heads of t he pronat or t eres muscle and under t he f ibrous arch of t he f lexor
digit orum superf icialis (pronator syndrome)[ 125, 224] . Nerve injury is especially
likely t o occur if t he nerve passes deep t o a hypert rophied pronat or t eres. This
syndrome has t he f ollow ing charact erist ics:
1. Pain may be present in t he proximal f orearm, especially on resist ance t o

pronat ion of t he f orearm and f lexion at t he w rist .
2. Tenderness is observed over t he pronat or t eres muscle on t he applicat ion of
deep pressure.
3. Frequent ly, t here is a lack of involvement of t he pronat or t eres, f lexor carpi
radialis, palmaris longus, and f lexor digit orum muscles because nerve
branches t o t hese muscles of t en depart f rom t he median nerve proper bef ore
t he sit e of nerve compression.
4. There is sparing of t he muscles innervat ed by t he ant erior int erosseous
nerve if t his nerve t akes a high origin f rom t he median t runk.
5. Parest hesias and sensory loss are observed in t he median f ield of
innervat ion (bot h palmar and digit al cut aneous areas).
6. At rophy and paresis of t he median t henar musculat ure occur.
7. Tinel's sign may be present .
The Anterior Interosseous Nerve Syndrome (Kiloh-

Nevin Syndrome)
I solat ed lesions of t his nerve [122, 125, 353] are not uncommon and may be due
t o st renuous exercise, t rauma, a f ibrous band const rict ing t he nerve, or an
accessory head of t he f lexor pollicis longus (G antzer's muscl e) ent rapping t he
nerve[ 274] . I njury t o t he nerve may f ollow cut dow n procedure (f or
cat het erizat ion) [103, 166, 294, 354] or venipunct ure[282] in t he ant ecubit al
f ossa or supracondylar f ract ures[70] . The nerve may also be involved as part of
t he Parsonage-Turner syndrome (neuralgic amyot rophy)[ 95, 265] , injured w hile
t he pat ient is in t he prone posit ion f or spinal surgery[8] , aff ect ed by vascular
anomalies[ 256] , or compressed by bronchogenic carcinoma met ast at ic t o t he
f orearm[ 245] . Bilat eral ant erior int erosseous nerve syndromes due t o
cyt omegalovirus inf ect ion have been described[91] . This purely mot or syndrome
has several charact erist ics:
1. Pain is present in t he proximal f orearm or arm last ing hours t o days.
2. Mild paresis of f orearm pronat ion (due t o pronat or quadrat us w eakness) is
observed. The
ant erior int erosseous nerve may rarely give rise t o t he nerve of t he pronat or
t eres muscle and, t heref ore, t he syndrome may rarely present w it h
w eakness of t he pronat or t eres[16] .
3. Paresis of f lexion of t he t erminal phalanges of t he second and t hird f ingers
(due t o paresis of t he f lexor digit orum prof undus I and I I ) is observed.
4. Paresis of f lexion of t he t erminal phalanx of t he t humb (due t o paresis of t he
f lexor pollicis longus) is observed.
5. There is a charact erist ic pi nch atti tude of t he hand w hile at t empt ing t o make
a f ull circle by applying t he pulp of t he t humb t o t hat of t he index f inger w it h
f irm pressure. This result s f rom w eakness of t he f lexor pollicis longus and
t he f lexor digit orum prof undus. There is hyperext ension of t he
int erphalangeal joint of t he t humb, inabilit y t o f lex t he dist al phalanges of t he
t humb and index f inger, and proximal approximat ion of t he t humb on t he index
f inger.
6. Normal sensat ion is observed.
Because t he ant erior int erosseous nerve has no cut aneous represent at ion, t his
syndrome is of t en considered a purely mot or syndrome. How ever, sensory f ibers
of t he w rist radiocarpal, radioulnar, int ercarpal, and carpomet acarpal joint s
t ravel in t he ant erior int erosseous nerve[83, 353] . I njury t o t he t erminal branch of
t he ant erior int erosseous nerve can cause persist ent , dull, aching volar w rist
pain[ 83] .
A pseudoanteri or i nterosseous nerve syndrome has been described[354] , w it h
part ial median nerve compromise at t he ant ecubit al level. The nerve bundles t hat
f orm t he ant erior int erosseous nerve are primarily involved, and t he mot or
f indings are t hose described w it h t he ant erior int erosseous nerve syndrome. The
ant erior int erosseous nerve f ascicle w it hin t he median lies post eriorly at t he
elbow and is, t heref ore, most prone t o injury by f ract ures at t his sit e[325] . O t her
median-innervat ed muscles are spared, and t he only clinical f inding bet raying a
more proximal median nerve lesion is some median dist ribut ion sensory change,
as t he sensory f ibers f rom t he index f inger and t humb also lie post eriorly[325] .
This syndrome has been not ed w it h supracondylar f ract ure of t he humerus,
proximal radial f ract ure, venipunct ure or art erial cat het erizat ion, and neuroma.
Median nerve ent rapment may occur in t he f orearm because of an accessory
bicipit al aponeurosis[316] or because of enlarged communicat ing veins direct ly
compressing t he median nerve[49] . O t her et iologies include art eriovenous
f ist ulas in pat ient s on chronic renal dialysis, f ract ures of t he ulna or radius, and
t umors[ 358] . This syndrome is charact erized by paresis or paralysis of muscles
innervat ed by t he ant erior int erosseous nerve as w ell as more proximal median-
innervat ed muscles (e. g. , pronat or t eres and f lexor carpi radialis). Sensat ion is
int act . Median nerve damage proximal t o t he carpal t unnel may occur in
w heelchair at hlet es[53] .
The Carpal Tunnel Syndrome

The median nerve is part icularly vulnerable t o compression as it passes int o t he
hand bet w een t he carpal bones and t he t ransverse carpal ligament (carpal
tunnel ) [76, 239, 271, 322] . The incidence of carpal t unnel syndrome is
increased among elect ronic-part s assemblers, f rozen-f ood processors,
musicians, cyclist s, w heelchair at hlet es, and dent al hygienist s; repet it ive w rist
movement s, vibrat ing t ools, aw kw ard w rist posit ions, and great f orce seem t o
correlat e w it h t his disorder[76] . Women are more commonly aff ect ed t han men.
The increased pressure w it hin t he carpal t unnel is usually caused by a
nonspecif ic f lexor t enosynovit is, but cert ain condit ions such as diabet es mellit us,
rheumat oid art hrit is, pregnancy[347] , amyloidosis, hypot hyroidism, acromegaly,
renal dialysis, and congenit al narrow ing of t he carpal canal, may predispose t o
t his syndrome. The f requency of carpal t unnel syndrome in comput er users is
surprisingly similar t o t hat in t he general populat ion[323] . A carpal t unnel–like
syndrome may also occur w it h compression of t he median nerve in t he dist al
f orearm, proximal t o t he carpal t unnel (e. g. , due t o a t hrombosed aneurysm of
t he epineural vessels)[ 47, 107] . The carpal t unnel syndrome usually consist s of
f our main sympt oms:
1. Bout s of pain or parest hesias in t he w rist and hand are observed t hat are
of t en most severe and t roublesome during t he hours of sleep and t hat are
relieved by shaking or rubbing t he involved hand. Alt hough t hese sympt oms
are usually localized t o t he w rist or median-innervat ed f ingers, t hey may
spread upw ard int o t he f orearm[126, 322] . For example, parest hesias and
pain occurred proximal t o t he w rist in 36. 5% of 255 pat ient s in one
st udy[ 322] . Pat ient s may also report sensory sympt oms in t he hand out side
t he median dist ribut ion (e. g. , in t he w hole hand, in an ulnar dist ribut ion, or in
a radial dist ribut ion), but sensory signs do not ext end beyond t he median
nerve dist ribut ion[126] . The sympt oms are bilat eral in over half t he cases but
usually appear f irst and are more severe in t he dominant hand.
2. Paresis and at rophy of t he abduct or pollicis brevis and opponens pollicis

muscles are present . Because t he opponens pollicis is occasionally
anomalously supplied by t he ulnar nerve, t his muscle may be spared. I n t he
carpal t unnel syndrome, t he lumbricals are of t en normal because, in t he
carpal t unnel, f ibers t hat innervat e t he lumbricals lie more post eriorly t han
t hose t o t he t henar muscles, prot ect ing t he lumbrical mot or f ibers f rom
compression[ 191] .
3. Sensory loss on t he radial palm, t he palmar aspect of t he f irst t hree-and-a-
half f ingers, and t he dorsal aspect of t he t erminal phalanges of t he second,
t hird, and half of t he f ourt h f ingers is not ed. This sensory loss is usually
most prominent in t he appropriat e f ingert ips. (Because t he palmar cut aneous
nerve t akes it s origin proximal t o t he w rist joint , t he sensat ion on t he t henar
eminence and proximoradial palm is spared. Theref ore, if t his area show s a
sensory loss, t he lesion is proximal t o t he w rist joint . ) Because of t he
f ascicular arrangement of median sensory f ibers in t he w rist , sensory
abnormalit ies may be limit ed t o one side of a digit or t o a w eb space
bet w een t w o digit s, f alsely suggest ing more dist al median sensory branch
impairment [ 325] .
4. I ncreased sensit ivit y of t he damaged nerve f ibers t o mechanical def ormat ion
is observed. Because of t his, various clinical t est s may help det ect a lesion
at t he carpal t unnel. Light percussion over t he median nerve at t he volar
surf ace of t he w rist may elicit a t ingling sensat ion radiat ing int o t he hand in
t he median dist ribut ion (Ti nel 's si gn). When a blood pressure cuff is applied
t o t he arm and compression is above syst olic pressure, median parest hesias
and pain may be aggravat ed (cuf f compressi on test of G i l l i att and Wi l son).
Flexion of t he w rist t o 90 degrees f or 30 t o 60 seconds may aggravat e
parest hesias and pain (Phal en's si gn) as may hyperext ension of t he w rist .
Lesions of the Palmar Cutaneous Branch of the Median

Nerve
The palmar cut aneous branch arises about 5 cm above t he w rist and courses
dist ally on t he radial side of t he palmaris longus t endon. I t passes
subcut aneously or t hrough a canal of it s ow n w it hin t he t ransverse carpal
ligament and t hen divides int o branches supplying t he skin over t he t henar
eminence. The nerve may be damaged by accident al lacerat ions and during
carpal t unnel surgery. O t her causes of neuropat hy include compression by an
abnormal palmaris longus muscle or by a ganglia and ent rapment by scars or
f ascial bands [10, 52, 113, 299, 321] . Damage t o t he nerve produces pain,
parest hesias, and numbness over t he t henar eminence. Median nerve
compression at t he w rist may occur w it h handcuff compression[121] .
Lesions within the Hand

Median nerve ent rapment in t he palm by t he head of t he lef t f irst met acarpal
bone w hile holding golf clubs may cause a sensory neuropat hy w it h hypest hesia
in a median dist ribut ion[144] . I njury t o t he deep palmar branches of t he median
nerve in t he dist al carpal canal (e. g. , by a palmar ganglion[164] ) or at t he t henar
eminence produces a purely mot or syndrome w it h w eakness and w ast ing of t he
t henar muscles (abduct or pollicis brevis, opponens pollicis, and superf icial head
of t he f lexor pollicis brevis) w it h no sensory abnormalit ies. Select ive acut e
demyelinat ion of t he recurrent t henar mot or branch of t he median nerve ow ing t o
vibrat ions f rom a sander (vi brati on-i nduced medi an neuropathy) may cause
w eakness in t he abduct or pollicis brevis w it hout sensory loss[162] .
Lesions of the Palmar Digital Branches of the Median

Nerve
The palmar digit al nerves are t he t erminal branches of t he median and ulnar
nerves (Fig. 2-6). The median nerve divides int o a number of branches af t er it
emerges f rom t he dist al end of t he carpal t unnel. Usually, it divides int o t w o
major branches, each of w hich t hen divides int o t he common di gi tal nerves,
w hich in t urn divides int o t w o proper di gi tal branches. The t w o palmar digit al
branches t o t he t humb and t o t he lat eral side of t he second digit usually arise
f rom t he lat eral t erminal division of t he median nerve. The ot her digit al branches
f rom t he median nerve arise f rom t he medial division and supply digit al branches
t o t he lat eral t hree-and-a-half digit s, but t he ent ire f ourt h digit may be innervat ed
by t he median or ulnar nerve.
Lesions of a common palmar digit al nerve in t he hand cause sensory sympt oms
and loss usually involving t he adjacent sides of t w o f ingers, depending on t he
nerve dist ribut ion. Damage t o a proper digit al branch produces sensory loss and
parest hesias rest rict ed t o t he side of t he f inger. Et iologies include t rauma (e. g. ,
lacerat ions, f inger dislocat ions, and f ract ures), compression f rom musical
inst rument s (e. g. , f l uti st's neuropathy), t endon sheat h cyst s and t umors,
t enosynovit is, nerve ischemia (e. g. , in diabet es), and nerve t umors [23, 74, 267] .
Bowl er's thumb is a digit al neuropat hy of t he palmar digit al branch t hat supplies
t he medial side of t he t humb due t o chronic compression
f rom a bow ling ball[86, 237] . This compression is usually due t o perineural
f ibrosis but , inf requent ly, a bow ler's t humb lesion is a t raumat ic neuroma caused
by t he prolif erat ion of f ibrous t issues, bot h around and w it hin t he digit al
nerve[ 237] . These phenomena are t he result of adapt ive changes in t he t humb in
response t o f requent insert ion and compression in t he holes of t he bow ling ball.
The clinical present at ion of t his condit ion may include parest hesias, hypest hesia,
changes in t w o-point discriminat ion sense, or a posit ive Tinel's sign in t he
dist ribut ion of t he involved digit al nerve, w hich may be t hick and f irm t o
palpat ion. This condit ion is most commonly described in bow ling ent husiast s,
alt hough similar involvement can be caused by ot her sport ing act ivit ies such as
baseball, by repet it ive use injuries, and f ollow ing f inger surgery[237] .
FI G URE 2-6 Palmar view of t he right hand show ing t he course of palmar
digit al branches of t he median and ulnar nerves.
Ulnar Nerve (C7–T1)

Anatomy
The ulnar nerve, a mixed nerve, (Fig. 2-7) is t he main branch of t he medial cord
of t he brachial plexus and derives f rom t he sevent h and eight h cervical and f irst
t horacic spinal root s. I t crosses t he axilla beneat h t he pect oralis minor muscle
and cont inues t o t he upper arm, w here it lies medial t o t he brachial art ery. I n t he
dist al arm it ent ers a groove bet w een t he medial humeral epicondyle and t he
olecranon process. The aponeurosis bet w een t he olecranon and medial
epicondyle f orms t he roof of an osseof ibrous canal (the cubi tal tunnel), t he f loor
of w hich is f ormed by t he medial ligament of t he elbow joint . I t t hen passes
bet w een t he humeral and ulnar heads of t he f lexor carpi ulnaris t o rest on t he
f lexor digit orum prof undus. I mmediat ely dist al t o t he elbow joint t he nerve
gives off it s f irst t w o muscular branches, t o t he f lexor carpi ulnaris and t he f lexor
digit orum prof undus I I I and I V, respect ively.
FI G URE 2-7 The ulnar nerve.
1. Fl exor Carpi Ul nari s (C7–T1). An ulnar f lexor of t he w rist . I t is t est ed by

having t he pat ient f lex and adduct t he hand at t he w rist against resist ance.
2. Fl exor Di gi torum Prof undus III and IV (C7–C8). A f lexor of t he t erminal
phalanges of t he f ourt h and f if t h f ingers. I t is t est ed by having t he pat ient
f lex t he dist al phalanx against resist ance w hile f ixing t he t hird phalanx.
The ulnar nerve t hen descends beneat h t he f lexor carpi ulnaris and, in t he dist al
f orearm, gives off t he pal mar cutaneous branch, w hich supplies t he skin over t he
hypot henar eminence. I t t hen gives off a dorsal cutaneous branch, w hich
supplies t he dorsal ulnar aspect of t he hand and t he dorsal aspect of t he f if t h
f inger and half of t he f ourt h f inger. The ulnar nerve proper t hen ent ers t he w rist
lat eral t o t he t endon of t he f lexor carpi ulnaris muscle. I n t he hand it gives off
t he superf i ci al termi nal branch, w hich is a sensory branch t o t he skin of t he
dist al part of t he ulnar aspect of t he palm and t he palmar aspect of t he f if t h and
half of t he f ourt h f inger, and t hen passes bet w een t he pisif orm carpal bone
medially and t he hook of t he hamat e carpal bone lat erally (ulnar t unnel or canal
of G uyon) as t he deep muscular branch. This deep branch supplies several
muscles:
1. Pal mari s brevi s (C8–T1). A cut aneous muscle at t he proximal border of t he

ulnar aspect of t he hand.
2. Abductor di gi ti mi ni mi (C8–Tl ). An abduct or of t he f if t h f inger. I t is t est ed by
having t he pat ient abduct t he f if t h f inger against resist ance w hile t he volar
aspect of t he hand is on a f lat surf ace.
3. O pponens di gi ti mi ni mi (C8–T1). An opposer of t he f if t h f inger.
4. Fl exor di gi ti mi ni mi (C8–T1). A f lexor of t he f if t h f inger. I t is t est ed by
having t he pat ient
f lex t he f if t h f inger at t he met acarpophalangeal joint against resist ance.

5. Lumbri cal s III and IV (C8–T1). Flexors of t he met acarpophalangeal joint s
and ext ensors of t he proximal int erphalangeal joint s of t he f if t h and f ourt h
f ingers. They are t est ed by having t he pat ient ext end t he proximal
int erphalangeal joint against resist ance, w it h t he met acarpophalangeal joint
hyperf lexed and f ixed.
6. Interosseous muscl es (C8–Tl ). Flexors of t he met acarpophalangeal joint s
and ext ensors of t he proximal int erphalangeal joint s. The f our dorsal
int erossei are f inger abduct ors, w hereas t he t hree palmar int erossei are
f inger adduct ors. They are t est ed by spreading or abduct ing t he f ingers
against resist ance. The median nerve innervat es t he f irst dorsal int erosseous
muscles in 1% of individuals. Rarely, t he f irst dorsal int erosseous muscle is
innervat ed by t he radial nerve (Froment -Rauber nerve). Rarely, all t henar
muscles, including t he opponens, may be innervat ed by t he ulnar nerve (al l -
ul nar motor hand)[ 109, 280] .
7. Adductor pol l i ci s (C8–T1). An adduct or of t he met acarpal of t he t humb. I t is
t est ed by having t he pat ient adduct t he t humb at right angles t o t he palm
against resist ance. The median nerve innervat es t his muscle in 2% of
individuals.
8. Deep head of the f l exor pol l i ci s brevi s (C8–Tl ). A f lexor of t he f irst phalanx
of t he t humb.
Nerve Lesions
Lesions above the Elbow
Processes causing damage t o t he ulnar nerve in t he axilla or upper arm may also
damage t he median and radial nerves (t riad neuropat hy). Nerve compression
may be caused by sleeping w it h t he arm hanging over a sharp edge or t he head
of a sleeping part ner compressing t he nerve against t he humerus, crut ches or
t ourniquet s, art eriovenous f ist ulas in dialysis pat ient s, aneurysms, hemat omas,
nerve t umors, and ot her masses[250, 331] . Supracondylar f ract ures of t he
humerus may also cause nerve injury[73, 146] .
Lesions of t he ulnar nerve above t he elbow (e. g. , a lesion of t he medial cord of
t he brachial plexus) produce t he f ollow ing signs:
1. Abnormal appearance of the hand. The hypot henar eminence and int erossei
are at rophied and f lat t ened. There is of t en a “claw -hand” def ormit y (mai n en
gri f f e), in w hich t he f if t h, f ourt h, and, t o a lesser ext ent , t he t hird f ingers are
hyperext ended at t he met acarpophalangeal joint s and f lexed at t he
int erphalangeal joint s. The hyperext ension at t he met acarpophalangeal joint s
is due t o paralysis of t he int erossei and ulnar lumbricals, w hich result s in
unopposed act ion of t he long f inger ext ensors (ext ensor digit orum); t he
f lexion at t he int erphalangeal joint s is due t o t he pull exert ed by t he long
f lexor t endons. Rarely, ulnar neuropat hy may init iat e or sust ain a specif ic
dyst onia t hat is manif est by t he f lexion of t he f ourt h and f if t h digit s[65] .
2. Paresi s or paral ysi s of the ul nar f l exi on. This applies t o t he ulnar f lexion of
t he w rist and of t he t erminal phalanges of t he f ourt h and f if t h f ingers, and at
t he met acarpophalangeal joint s of t he second t o f if t h f ingers. Ulnar paresis
also aff ect s ext ension at t he int erphalangeal joint s of t he second t o f if t h
f ingers, adduct ion and abduct ion of t he second t o f if t h f ingers, and abduct ion
and opposit ion of t he f if t h f inger. As a result of adduct or pollicis aff ect ion,
Froment's prehensi l e thumb si gn (si gne du journal ) may be present (w hen a
sheet of paper is grasped bet w een t he t humb and index f inger and pulled,
t he proximal phalanx of t he t humb is ext ended and t he dist al phalanx is
f lexed if an ulnar nerve lesion is present ).
I n 15% t o 31% of subject s, a median-ulnar communicat ion exist s (Marti n-
G ruber anastomosi s)[ 127, 187] in w hich axons descending in t he median or
ant erior int erosseous nerve cross t hrough t he f orearm t o join t he ulnar nerve
at t he w rist . The median f ibers ult imat ely innervat e t he int rinsic hand
muscles, especially t he f irst dorsal int erosseous, adduct or pollicis, and
hypot henar muscles. Theref ore, if a pat ient has an ulnar neuropat hy above
t he f orearm, t hese muscles may be spared or minimally involved if a median-
ulnar communicat ion is present . The ent ry point of t he crossing f ibers f rom
t he median t o t he ulnar nerve usually occurs 3 t o 10 cm dist al t o t he medial
humeral epicondyle[343] . Ulnar-t o-median communicat ions in t he
f orearm[ 327] and t hose of only sensory f ibers[140] may rarely occur. The
overall incidence of Mart in-G ruber anast omoses is approximat ely 17%[ 187] .
Four t ypes of connect ions exist : t ype 1 (60%) send mot or branches f rom t he
median t o t he ulnar nerve t o innervat e “median” muscles; t ype I I (35%) send
mot or branches f rom median t o ulnar nerves t o innervat e “ulnar” muscles;
t ype I I I (3%) send mot or f ibers f rom t he ulnar t o t he median nerve t o
innervat e median muscles; and t ype I V (1%) send mot or f ibers f rom t he ulnar
t o t he median nerve t o innervat e ulnar muscles.
3. Sensory f i ndi ngs. Because all t hree sensory branches of t he ulnar nerve are
aff ect ed (palmar, dorsal, and superf icial t erminal cut aneous branches),
parest hesias and sensory loss occur on t he dorsal and palmar surf aces of
t he f if t h and ulnar half of t he f ourt h f inger and t he ulnar port ion of t he hand
t o t he w rist .
Lesions at the Elbow (Cubital Tunnel Syndrome)

The ulnar nerve is most commonly compressed at t he elbow in t he cubit al t unnel
[ 26, 27, 48, 76, 216, 217] because t his t unnel narrow s during movement ,
especially elbow f lexion. Nerve ent rapment is due t o t he t hickening of t he
aponeurot ic arch (t he humero-ulnar aponeurot ic arcade) bet w een t he t w o heads
of t he f lexor carpi ulnaris or bulging of t he medial collat eral ligament of t he
elbow joint (f loor of t he cubit al t unnel)[ 58] . The nerve may also be ent rapped by
a ganglion cyst or ot her mass of t he elbow (e. g. , int raneural perineuroma), by
dense f ibrous bands bridged direct ly bet w een t he medial epicondyle and t he
olecranon proximal t o t he cubit al t unnel proper, by an accessory anconeus
epit rochlearis muscle, by supracondylar spurs, or at it s point of exit f rom t he
f lexor carpi ulnaris muscle dist ally by a t hickened muscular sept um bet w een t he
f lexor carpi ulnaris and t he f lexor digit orum prof undus [25, 58, 59] . Pat ient s w it h
end-st age renal disease receiving hemodialysis may be especially predisposed
t o ulnar neuropat hy by f act ors such as arm posit ioning during hemodialysis,
underlying polyneuropat hy, and upper ext remit y vascular access[231] .
The ulnar nerve at t he elbow is also subject t o ext ernal t rauma, especially during
coma or general anest hesia[137, 186] and may be severed by missile
injury[ 372] . Def ormit y f rom previous elbow injuries may lead t o a nerve st ret ch,
event ually producing signs and sympt oms long af t er t he original injury (tardy
ul nar nerve pal sy). The syndrome produced by t hese lesions is t he same as t hat
described previously in Lesions above t he Elbow. A reliable sign of ulnar
ent rapment by t he f lexor carpi ulnaris muscle is t he ul nar f l exi on maneuver[ 102] ,
in w hich increased parest hesias in t he f ourt h and f if t h digit s f ollow 3 minut es of
elbow and w rist f lexion in ulnar deviat ion.
The main clinical f eat ures of t he cubit al t unnel syndrome, w hich diff erent iat e it
f rom t ardy ulnar nerve palsy, are[217] :
1. No evidence of joint def ormit y or prior t rauma

2. Frequent occurrence of bilat eral sympt oms and signs of ulnar neuropat hy
3. A t aut , palpably enlarged nerve in t he ulnar groove
4. Elect rophysiologic (elect romyographic) localizat ion t o t he cubit al t unnel
5. O perat ive f indings of a sw ollen, t aut , hyperemic nerve, dist ally limit ed by t he
proximal border of t he aponeurosis joining t he t w o heads of t he f lexor carpi
ulnaris muscle.
Ulnar neuropat hy at t he elbow of t en spares t he f lexor carpi ulnaris muscle. This
w as t hought t o occur because t he nerve branches t o t he f lexor carpi ulnaris may
arise at or proximal t o t he medial epicondyle (in 10% of individuals), but t he
involvement of f lexor carpi ulnaris more of t en correlat es w it h t he severit y of t he
neuropat hy and w it h w het her compression is ret roepicondylic or at t he humero-
ulnar aponeurot ic arcade[57] . Sparing of t he f lexor carpi ulnaris w it h ulnar
neuropat hy at t he elbow is unrelat ed t o t he level of origin of it s innervat ing
branch but rat her relat ed t o t he int ernal t opography of t he nerve, t he severit y of
compression, and t he level of compression[57, 325] . Ulnar neuropat hy at t he
elbow may pref erent ially compress t he nerve f ascicle t o dist al hand muscles
w hile sparing t he sensory branches as w ell as t he mot or f ascicle t o t he more
proximal f lexor carpi ulnaris and f lexor digit orum prof undus, t hereby mimicking a
G uyon's canal ulnar neuropat hy w hen t he lesion is, in f act , at t he elbow [325] .
Lesions in the Forearm

Et iologies of ulnar nerve compression in t he f orearm include a hypert rophied
f lexor carpi ulnaris muscle, f ibrous and f ibrovascular bands, hemat omas, and
handcuff s [56, 57, 139, 290] . Ulnar nerve ent rapment at t he f orearm or w rist
may occur in w heelchair at hlet es[53] . Damage may also occur w it h f ract ures of
f orearm bones (e. g. , Colles' f ract ure)[ 274, 341] . I schemic neuropat hy may occur
in pat ient s w it h art eriovenous shunt s f or dialysis[358] . The clinical f eat ures are
as explained earlier f or Lesions above t he Elbow except t hat t he f lexor carpi
ulnaris and t he f lexor digit orum prof undus I and I I muscles are of t en spared. I n a
pat ient w it h surgical sect ion of t he dist al ulnar nerve in t he f orearm, ulnar
sensat ion in t he dorsal hand w as spared in relat ion t o t he superf icial radial
sensory innervat ion of t he ulnar hand dorsum (“paradoxical” preservat ion of ulnar
sensory f unct ion)[ 208] .
Lesions at the Wrist and in the Hand

An ulnar lesion at t he w rist [296] causes t he same mot or f indings as a lesion at a
more proximal level, except t hat t he f lexor carpi ulnaris and t he f lexor digit orum
prof undus I I I and I V are spared. The sensory f indings depend on t he locat ion of
t he nerve lesion w it h respect t o t he sit es of origin
of t he palmar and dorsal cut aneous branches. I f t he lesion is dist al t o t hese t w o

branches, t he sensory loss is rest rict ed t o t he dist al palm and t he palmar
surf aces of t he f if t h f inger and t he medial f ourt h f inger (t he area of supply of t he
superf icial t erminal cut aneous branch). The proximal palmar area and t he ent ire
dorsum of t he hand are t hen spared.
Ebeling, G illiat t , and Thomas have divided lesions of t he ulnar nerve in t he hand
int o t hree groups[92] :
1. Compression of t he nerve as it ent ers t he hand. All of t he ulnar-innervat ed

muscles of t he hand are aff ect ed, and because t he lesion is proximal t o t he
superf icial t erminal cut aneous nerve, t here is sensory loss on t he dist al palm
and t he palmar surf aces of t he f if t h f inger and t he medial half of t he f ourt h
f inger.
2. Compression of t he proximal part of t he t erminal mot or branch (usually due
t o nerve compression w it hin t he canal of G uyon or pisohamat e t unnel)[ 261] .
I n t hese purely mot or lesions, all t he hand muscles innervat ed by t he ulnar
nerve are aff ect ed. Because t he lesion is dist al t o t he superf icial t erminal
cut aneous branch, t here is no sensory loss.
3. Dist al compression of t he t erminal mot or branch of t he ulnar nerve. This
purely mot or lesion is dist al t o t he sit e of origin of t he mot or f ibers of t he
hypot henar muscles and is also dist al t o all sensory branches[152] . I t
t heref ore result s in paresis and at rophy of t he int erossei, t he medial t w o
lumbricals, t he deep head of t he f lexor pollicis brevis, and t he adduct or
pollicis muscles only.
O t hers have divided ulnar lesions at t he w rist and hand int o f our groups[60] :
Type 1. Weakness of all ulnar int rinsic hand muscles and ulnar sensory
impairment (dorsal ulnar sensory branch dist ribut ion not involved) caused by
compression (e. g. , by a carpal ganglion[115] ) just proximal t o or w it hin t he
G uyon's canal (bot h superf icial and deep branches aff ect ed).
Type 2. Weakness of muscles innervat ed by a deep ulnar branch (including
hypot henar) ow ing t o it s compression at it s origin, but normal sensat ion.
Type 3. Weakness of muscles innervat ed by a deep ulnar branch w it h sparing
of hypot henar muscles ow ing t o it s compression dist al t o branches
innervat ing t he hypot henar muscles[152] .
Type 4. Compression at t he dist al end of t he G uyon's canal, result ing in t he
sensory branch alone being aff ect ed.
Ulnar nerve compression at t he w rist or hand is most f requent ly caused by a

ganglion f rom one of t he carpal joint s f ollow ed by occupat ional neuropat hy,
lacerat ion, ulnar art ery disease (e. g. , aneurysm), or carpal bone f ract ure [115,
152, 296] . O t her causes include lipoma, ext ernal pressure, nerve t umor, and
rheumat oid cyst [79, 105, 261, 369] . These pat ient s present w it h obvious
at rophy of t he f irst dorsal int erosseous and adduct or muscles w it hout sensory
changes. I n pat ient s w ho developed an ulnar neuropat hy af t er kidney t ransplant
surgery, t he presence of an art eriovenous shunt in t he hand may have played a
role[ 373] . A rare cause of ulnar compression in t he G uyon's canal is calcinosis in
scleroderma[ 337] . The mot or branch of t he ulnar nerve may be compressed by
t he arch of origin of t he adduct or pollicis muscle at t he point w here t he nerve
crosses t he t hird met acarpal or w here t he nerve penet rat es t he adduct or
muscle[ 276] .
Pal mari s brevi s spasm syndrome has been described t o occur f ollow ing t he
prolonged use of a comput er mouse and keyboard[188] . Elect rophysiologic
st udies suggest a dist al ulnar mot or branch lesion.
Lesions of the Dorsal Cutaneous Branch of the Ulnar

Nerve
The dorsal cut aneous branch arises above t he w rist and w inds medially around
t he ulna, deep t o t he t endon of t he f lexor carpi ulnaris muscle. I t supplies t he
skin of t he dorsum of t he hand and t he f if t h f inger. Damage t o t his branch may
occur w it h blunt t rauma, lacerat ions, handcuff s (handcuf f neuropathy), w rist
surgery, vein inject ion in addict s, and repet it ive w rist movement s in a person
using a code-sensing machine at a checkout count er (pri cer pal sy) [121, 133,
297, 298, 352] . Nerve ent rapment may occur w here t he nerve passes under t he
f lexor carpi ulnaris t endon[112] . Pain and ot her sensory dist urbances occur in
t he dist ribut ion of t he nerve.
Lesions of the Palmar and Dorsal Digital Branches of

the Ulnar Nerve
As not ed above, t he palmar digit al nerves are t he t erminal branches of t he
median and ulnar nerves (Fig. 2-6). The superf icial t erminal branch of t he ulnar
nerve arises w it hin t he G uyon's canal, passes int o t he hand, and divides int o
t hree palmar digit al branches t hat supply t he f if t h digit and t he ulnar half of t he
f ourt h digit (Fig. 2-6). Sensory loss and sympt oms may aff ect t he medial and
lat eral palmar aspect s of t he f if t h
digit and t he ulnar half of t he f ourt h digit , t he ulnar aspect of t he f ourt h digit and
t he medial half of t he f if t h digit , or t he ulnar half of t he f ourt h digit , t he medial
half of t he f if t h digit , or t he ulnar half of t he f if t h digit in isolat ion, depending on
t he locat ion of t he nerve injury. The dorsal digit al nerves are f ormed f rom t he
branches of t he superf icial radial and dorsal ulnar cut aneous nerves. The dorsal
ulnar cut aneous nerve sends dorsal digit al branches t o t he dorsum of t he ulnar
half of t he f ourt h digit and t he medial and lat eral halves of t he dorsum of t he f if t h
digit (Fig. 2-8). Et iologies of palmar and dorsal digit al neuropat hies are as
discussed under Lesions of t he Palmar Digit al Branches of t he Median Nerve.
FI G URE 2-8 Dorsal view of t he right hand, show ing t he dorsal digit al nerves
f ormed f rom t he superf icial radial and dorsal ulnar cut aneous nerves.
Pseudoulnar Nerve Palsy

Pseudoulnar nerve palsy ref ers t o isolat ed hand w eakness apparent ly in an ulnar
dist ribut ion t hat is due t o cont ralat eral cerebral inf arct ion in t he w hit e mat t er of
t he angular gyrus of t he inf erior pariet al lobe[338] . Pat ient s w it h t his condit ion
are f ound t o have cont ralat eral carot id art ery st enosis. I solat ed “ulnar” sensory
loss and hand w eakness may also occur w it h inf arct ion, aff ect ing t he
cont ralat eral precent ral gyrus and ant erior aspect of t he post cent ral gyrus[247] ,
and pseudoulnar sensory loss may occur w it h small cort ical inf arct ion of t he
midport ion of t he post cent ral gyrus[61] .
Radial Nerve (C5–C8)

Anatomy
The radial nerve, a mixed nerve, (Fig. 2-9) derives f rom t he post erior cord of t he
brachial plexus and comprises f ibers f rom t he spinal levels C5–C8. Af t er
descending post erior t o t he axillary art ery, bet w een t he long and medial heads of
t he t riceps, it t hen cont inues dist ally in t he spiral groove of t he humerus (in
cont act w it h t he bone or separat ed f rom it by some f ibers of t he medial head of
t he t riceps).
I n t he axilla, t he nerve gives rise t o t he posteri or cutaneous nerve of the arm,
w hich supplies t he skin over t he post erior aspect of t he arm as
f ar dow n as t he olecranon. A secondary sensory branch, t he posteri or cutaneous

nerve of the f orearm, arises eit her w it hin or proximal t o t he spiral groove and
innervat es t he skin on t he dist al ext ensor aspect of t he arm and t hat of t he
f orearm up t o t he w rist . Wit hin or proximal t o t he spiral groove, t w o mot or
branches are given off . They supply t he f ollow ing t w o muscles:
FI G URE 2-9 The radial nerve.
1. Tri ceps (C6–C8), a f orearm ext ensor subserving t he t riceps ref lex. This
muscle is t est ed by having t he pat ient ext end t he f orearm at t he elbow
against resist ance.
2. Anconeus (C6–C8), a f orearm ext ensor.
Af t er it s course in t he spiral groove, t he radial nerve reaches t he lat eral aspect

of t he humerus and pierces t he lat eral int ermuscular sept um t o occupy a posit ion
in f ront of t he lat eral condyle of t he humerus bet w een t he brachialis and
brachioradialis muscles. Here it supplies t he f ollow ing muscles:
1. Brachi al i s (C5–C6), an elbow f lexor. I t is also innervat ed by t he

musculocut aneous nerve.
2. Brachi oradi al i s (C5–C6), a f orearm f lexor. I t is t est ed by having t he pat ient
f lex t he f orearm against resist ance, w it h t he f orearm midw ay
bet w een pronat ion and supinat ion. This muscle subserves t he radial ref lex.
3. Extensor carpi radi al i s l ongus (C5–C6), a radial ext ensor of t he hand. I t is
t est ed by having t he pat ient ext end and abduct t he hand against resist ance.
The radial t runk t hen bif urcat es int o a superf icial branch and a deep branch. The
superf i ci al branch passes over t he origin of t he ext ensor carpi radialis brevis
and dow n t he f orearm under t he brachioradialis. I t emerges in t he dist al f orearm,
as t he dorsal di gi tal nerve, and supplies t he skin on t he medial aspect of t he
back of t he hand and t he dorsum of t he f irst f our f ingers (t he aut onomous zone
of supply is t he skin over t he f irst int erosseous space).
The deep branch passes t hrough t he f ibrous edge of t he ext ensor carpi radialis
by means of a slit in t he supinat or muscle hse (arcade of Frohse) t o t he
post erior f orearm. I n t he f orearm, it is in cont act w it h t he int erosseous
membrane and is ref erred t o as t he posteri or i nterosseous nerve. This purely
mot or nerve innervat es t he f ollow ing muscles:
1. Supi nator (C6–C7), a f orearm supinat or t hat is t est ed by having t he pat ient
supinat e t he f orearm against resist ance.
2. Extensor carpi radi al i s brevi s (C5–C7), a radial ext ensor of t he hand.
3. Extensor di gi torum (C7–C8), an ext ensor of t he met acarpophalangeal joint s
of t he second t hrough t he f if t h f ingers. I t is t est ed by having t he pat ient
ext end t he met acarpophalangeal joint s against resist ance.
4. Extensor di gi ti mi ni mi (C7–C8), an ext ensor of t he met acarpophalangeal
joint of t he f if t h f inger.
5. Extensor carpi ul nari s (C7–C8), an ulnar ext ensor of t he hand t hat is t est ed
by having t he pat ient ext end and adduct t he hand at t he w rist against
resist ance.
6. Abductor pol l i ci s l ongus (C7–C8), an abduct or of t he met acarpal of t he
t humb. I t is t est ed by having t he pat ient abduct t he carpomet acarpal joint in
a plane at right angles t o t he palm.
7. Extensor pol l i ci s l ongus (C7–C8), an ext ensor of t he t humb. I t is t est ed by
ext ending t he t humb at t he int erphalangeal joint in a plane at right angles t o
t he palm.
8. Extensor pol l i ci s brevi s (C7–C8), an ext ensor of t he t humb t hat is t est ed by
having t he pat ient ext end t he t humb at t he met acarpophalangeal joint against
resist ance.
9. Extensor i ndi ci s (C7–C8), an ext ensor of t he second f inger.
Nerve Lesions
Lesions in the Axilla
Lesions of t he post erior cord of t he brachial plexus or high axillary lesions (e. g. ,
due t o crut ches, shoulder dislocat ion, missle injuries) aff ect all t he sensory and
mot or branches of t he radial nerve. Lesions of t he radial nerve at t his locat ion
have been described as being due t o nerve injury f rom t he “w indmill” pit ching
mot ion of compet it ive sof t ball (wi ndmi l l pi tcher's radi al neuropathy)[ 304] . The
f ollow ing sympt oms are observed:
Abnormal appearance of the hand. Charact erist ically, t he hand hangs in

f lexion (wri st drop). There is w ast ing of t he dorsal arm (t riceps) and muscle
mass on t he post erior surf ace of t he f orearm.
Motor l oss. There is paresis or paralysis of ext ension of t he elbow, ext ension
of t he w rist , supinat ion of t he f orearm, ext ension of all f ive
met acarpophalangeal joint s, and ext ension and abduct ion of t he
int erphalangeal joint of t he t humb. Elbow f lexion t ends t o be w eak. Abduct ion
of t he f ingers is w eak because t he dorsal int erossei require w rist f lexion f or
t heir proper act ion. Ulnar involvement might be mist akenly assumed f rom t his
f inding.
Ref l exes si gns. There is hyporef lexia or aref lexia of t he t riceps (C6–C8) and
radial (C5–C6) ref lexes.
Sensory l oss. There are parest hesias and sensory loss on t he ent ire
ext ensor surf ace of t he arm and f orearm and on t he back of t he hand and
dorsum of t he f irst f our f ingers.
Lesions of the Posterior Cutaneous Nerve of the Arm

and Forearm
Ent rapment of t he post erior cut aneous nerve of t he arm result ing in burning and
t ingling over t he low er post erior arm may occur w hen t he arm is draw n across
t he f ront of t he body and t he elbow is vigorously ext ended[197] . This purely
sensory syndrome is likely due t o t he nerve st ret ch by t ension f rom t he long
head of t he t riceps w it h ext ension during t he above maneuvers, but it could also
be due t o post erior cut aneous nerve ent rapment by t he lat eral head of t he
t riceps. I solat ed injury of t he post erior cut aneous nerve of t he arm or f orearm
may also be caused by inject ion, t ourniquet applicat ion, arm injuries, and
surgical procedures [62, 64, 88] .
Lesions within the Spiral Groove of the Humerus

Lesions at t his locat ion are usually due t o humeral f ract ures[104] or compressive
lesions[ 50] (Saturday ni ght pal sy). The most common present at ion
of acut e ret rohumeral compression is one in w hich t he subject w akens, of t en

f rom a deep sleep (made deeper and perhaps more prot ract ed by alcohol or
sedat ives), t o f ind t hat he or she is unable t o ext end t he w rist [50] . Tourniquet
paralysis of t he radial nerve may also occur. New borns may have radial
neuropat hies relat ed t o f ract ures, lacerat ions, compression, or ent rapment [97] .
The radial nerve may also be ent rapped by a musculot endinous arch of t he
lat eral head of t he t riceps muscle[229] or damaged af t er repet it ive arm exercise
w hen a sudden f orcef ul cont ract ion and st ret ch of t he arm muscles result s in a
delayed upper arm radial nerve palsy[328] . Soldiers may develop radial nerve
palsies at t he lat eral border of t he humerus af t er milit ary shoot ing t raining ow ing
t o t he persist ent kneeling shoot ing post ure[302] . The w indmill pit ching mot ion of
compet it ive sof t ball may also injure t he nerve in t he spiral groove (anot her f orm
of wi ndmi l l pi tcher's radi al neuropathy)[ 304] . These pat ient s have t he same
sympt oms as t hose described previously f or Lesions in t he Axilla, except f or t he
f ollow ing modif icat ions:
1. Sensibilit y on t he ext ensor aspect of t he arm is spared because t his nerve

usually arises high in t he axilla.
2. Sensibilit y on t he ext ensor aspect of t he f orearm may or may not be spared,
depending on t he sit e of origin of t his nerve f rom t he radial nerve proper.
3. The t riceps muscle (and t heref ore t he t riceps ref lex) is spared because t he
branches t o t he muscle have a proximal origin. The anconeus muscle is t he
most dist al muscle spared in radial spiral groove lesions.
Diff erent ial involvement of t he radial nerve f ascicles along t he spiral groove in
“Sat urday night palsy” might explain t he variable presence of brachialis
w eakness or sensory impairment , eit her of w hich may be absent [325] .
Lesions dist al t o t he spiral groove and t o t he sit e of origin of t he brachioradialis
and ext ensor carpi radialis longus (prior t o t he bif urcat ion of t he nerve) have
sympt oms t hat are similar t o t hose seen w it h a spiral groove lesion, w it h t he
f ollow ing except ions:
1. The brachioradialis and ext ensor carpi radialis longus muscles are spared.
2. The radial ref lex is spared.
3. Sensibilit y on t he ext ensor surf ace of t he f orearm (post erior cut aneous nerve
of t he f orearm) is more likely t o be spared.
Progressive, severe, painless radial neuropat hy may occur as a delayed

complicat ion of chronic int ramuscular inject ion[214] . I n pat ient s w it h t hese
sympt oms, an explorat ion of t he radial nerve revealed mult if ocal ent rapment
w it hin t he densely f ibrot ic t riceps muscle at sit es bet w een t he spiral groove and
t he dist al course of t he radial nerve near t he elbow (chronic inject ion-induced
t riceps f ibrosis).
Lesions at the Elbow

The post erior int erosseous nerve (deep mot or branch of t he radial nerve) may be
injured or ent rapped at t he elbow [71, 100] . Ent rapment may be caused by t he
f ollow ing:
1. A const rict ing band at t he radiohumeral joint capsule

2. The sharp edge of t he ext ensor carpi radialis brevis muscle
3. A f ibrot endinous arch w here t he nerve ent ers t he supinat or muscle (arcade
of Frohse)[ 51, 314]
4. I t s occurrence w it hin t he subst ance of t he supinat or muscle (supi nator
channel syndrome)
5. O t her et iologies[71] , such as lacerat ions and gunshot w ounds; closed injuries
due t o f ract ures of t he proximal radius or bot h radius and ulna; chronic
repeat ed t rauma relat ed t o st ressf ul supinat ion and pronat ion in sw immers,
f risbee players, t ennis players, violinist s, and orchest ra conduct ors [100,
185, 196] ; nerve compression by t he repet it ive movement s of t he f orearm
(uphol sterer's posteri or i nterosseous neuropathy)[ 363] ; carrying a knapsack
support ed by a hyperpronat ed and ext ended w rist w it h t he elbow in a f lexed
posit ion (knapsack paral ysi s)[ 254] ; t he use of a Canadian (Lof st rand)
crut ch[ 111] ; brachiocephalic art eriovenous f ist ula const rict ion (due t o severe
compression f rom a hypert rophied venous limb of t he art eriovenous f ist ula)
[ 287] , iat rogenic due t o radial head resect ion and injury secondary t o t umor
removal; rheumat oid art hrit is[251] ; local mass (e. g. , lipoma, f ibroma,
ganglia, t raumat ic aneurysm of t he post erior int erosseous art ery, chondroma,
neurof ibroma, schw annoma)[ 100, 364] ; and amyloid neuropat hy w it h mult iple
myeloma[ 277] .
When t he post erior int erosseous nerve is damaged at t hese locat ions, t he
supinat or muscle and t he superf icial sensory branch of t he radial nerve are of t en
spared. Pat ient s w it h t his condit ion have at rophy and paresis of t he ext ensor
carpi ulnaris, ext ensor digit orum, ext ensor digit i minimi, abduct or pollicis longus
and brevis, and ext ensor indicis. Because t he ext ensor carpi radialis is
unaff ect ed w hile t he ext ensor carpi ulnaris is paret ic, t he w rist deviat es radially,
especially w hen t he pat ient
at t empt s t o make a f ist . The pat ient has diff icult y in ext ending t he
met acarpophalangeal joint s of all f ive f ingers (drop-f i nger def ormi ty), ext ending
t he w rist in an ulnar direct ion, ext ending t he int erphalangeal joint of t he t humb,
and abduct ing t he t humb. O ccasionally, an isolat ed paralysis of t he descending
mot or branch of t he post erior int erosseous nerve may occur (e. g. , due t o
const rict ion in t he dist al port ion of t he supinat or muscle), result ing in a “drop-
t humb” def ormit y ow ing t o paresis of t he ext ensor pollicis longus and brevis and
abduct or pollicis longus (t he ext ensor indicis may also be involved)[ 135] .
Some pat ient s w it h radial or post erior int erosseous nerve palsy demonst rat e
apparent w eakness of ulnar-innervat ed muscles, such as t he dorsal and palmar
int erossei and t he abduct or digit i minimi muscles[281] . These muscles insert on
t he ext ensor expansions, and t heir act ivat ion is associat ed w it h concomit ant
cont ract ion of f inger f lexors and ext ensors. This apparent w eakness may be due
t o t heir unopposed t ract ion on t he ext ensor expansion by t he paralyzed ext ensor
digit orum[ 281] .
A f ocal myopathy t hat causes w eakness of ext ension of t he right index, middle,
and f ourt h f ingers at t he met acarpal–phalangeal joint s w it h no sensory def icit ,
t hereby mimicking a post erior int erosseous nerve syndrome, has been
described[ 96] .
Lesions of the Superficial Branch of the Radial Nerve

(Cheiralgia Paresthetica)
The superf icial cut aneous branch of t he radial nerve may be injured anyw here
along it s locat ion in t he f orearm, result ing in a pure sensory syndrome
(parest hesias and sensory loss) t hat aff ect s t he radial part of t he dorsum of t he
hand and t he dorsal aspect of t he f irst t hree-and-a-half f ingers. This neuropat hy
is somet imes called Wartenberg's syndrome or chei ral gi a parestheti ca. (The
aut onomous zone of sensory loss occurs on t he area of skin covering t he f irst
int erosseous space. ) Radial sensory ent rapment [82] usually occurs w it h crush or
t w ist ing injuries t o t he w rist or f orearm or may f ollow repet it ive pronat ion–
supinat ion movement s required in cert ain occupat ions. Pain or burning over t he
dorsomedial w rist w it h t his ent rapment is aggravat ed by pinching and gripping
act ivit ies, and a posit ive Tinel's sign may occur w it h percussion over t he radial
sensory nerve, especially w here it exit s f rom t he deep f ascia. The
hyperpronat ion provocat ive t est (pronat ion of t he f orearm w it h t he ulnar f lexion
of t he w rist ) is of t en posit ive. The superf icial cut aneous branch may also be
ent rapped in t he f orearm bet w een t he t endons of t he brachioradialis and
ext ensor carpi radialis muscles (here t he nerve t ransit s f rom t he deep t o t he
superf icial branch)[ 81, 313] . The nerve may be injured by handcuff s compressing
t he nerve against t he dist al radius (a t ype of handcuf f neuropathy) [121, 202,
326] ; by compression f rom w rist w at ch bands, bracelet s, roped hands, or a cast ;
by direct nerve t rauma or f orearm lacerat ions; by nerve t umors; or as a
complicat ion of de Q uervain's t enosynovect omy.
Lesions of the Dorsal Digital Nerves

As not ed in t he preceding t ext , t he dorsal digit al nerves are f ormed f rom t he
superf icial radial nerve and t he dorsal cut aneous branch of t he ulnar nerve (Fig.
2-8). The dorsal digit al nerves t hat arise f rom f our or f ive t erminal branches of
t he superf icial branch of t he radial nerve supply t he dorsal aspect of t he t humb
(t hrough t w o branches) and t he dorsal aspect s of t he second and t hird digit s and
t he medial f ourt h digit . Sensory signs and sympt oms occur in t he dist ribut ion of
t he involved branches. For example, parest hesias and sensory loss conf ined t o
t he radial side of t he t humb may occur w it h a lesion of t he dist al dorsal digit al
nerve (in t he t humb)[ 207] . Et iologies of dorsal digit al neuropat hies are as
described earlier under Lesions of t he Palmar Digit al Branches of t he Median
Nerve.
Pseudoradial Nerve Palsy

I solat ed f laccid w eakness of t he hand, predominant ly aff ect ing t he w rist
ext ensors and causing w rist drop, may rarely be due t o a cerebral cort ical
inf arct locat ed in t he precent ral “hand knob” area[19] .
Medial Cutaneous Nerves of the Arm and Forearm (C8–

T1)
Anatomy
These t w o purely sensory branches arise f rom t he medial cord of t he brachial
plexus. The medial cut aneous nerve of t he arm supplies t he skin of t he axilla and
t he medial part of t he arm. The medial cut aneous nerve of t he f orearm divides
above t he elbow int o ant erior and post erior divisions t hat supply t he skin of t he
ant eromedial and post eromedial f orearms, respect ively, dow n t o t he w rist .
Nerve Lesions
I njuries t o t he medial cut aneous nerve of t he arm and f orearm nerves may occur
in t he axilla, aff ect ing t he medial cord of t he brachial plexus. A sensory loss
occurs in t he dist ribut ion of t he individual nerve branches. The medial cut aneous
nerve of t he f orearm may be aff ect ed in isolat ion by a st ret ch injury or by injury
due t o t he placement of an art erial graf t [63] . The nerve may also be damaged as
a complicat ion of an ulnar nerve surgery at t he elbow [80] .
Iliohypogastric (T12–L1), Ilioinguinal (L1), and

Genitofemoral (L1–L2) Nerves
Anatomy and Nerve Lesions
The mixed i l i ohypogastri c nerve arises f rom t he ant erior rami of spinal root
segment s T12 and L1. The nerve runs across t he psoas muscle and t hen behind
t he kidney, crossing t he quadrat us lumborum muscle and reaching t he iliac crest .
I t t hen pierces t he int ernal oblique and t ransversus abdominis muscles, bot h of
w hich it supplies. I t t erminat es in t he l ateral cutaneous branch a sensory nerve
t hat supplies t he skin over t he out er but t ock and hip, and t he anteri or cutaneous
branch a sensory branch t hat supplies t he ant erior abdominal w all above t he
pubis.
This nerve may be injured in t he lumbar plexus, at t he post erior or ant erior
abdominal w all, or dist ally near t he inguinal ring. Lesions of t his nerve result in
lit t le mot or def icit but lead t o pain or sensory loss in t he area of t he cut aneous
supply of t he nerve. Painf ul iliohypogast ric neuropat hies are not uncommon af t er
low er abdominal surgery[330] .
The mixed i l i oi ngui nal nerve arises f rom t he ant erior ramus of t he f irst lumbar
spinal segment w it hin t he psoas muscle. I t runs lat erally and dow nw ard, parallel
w it h t he iliohypogast ric nerve, t o reach t he iliac crest . This nerve, like t he
iliohypogast ric, supplies t he int ernal oblique and t ransversus abdominis muscles.
Af t er piercing t hese t w o muscles, it ent ers t he inguinal canal and passes t o t he
superf icial inguinal ring, f rom w hich it s sensory f ibers emerge. These f ibers are
dist ribut ed t o t he skin of t he medial t high below t he inguinal ligament as w ell as
t o t he skin of t he symphysis pubis and t he ext ernal genit alia.
This nerve may be injured in t he lumbar plexus, at t he post erior abdominal w all,
at t he ant erior abdominal w all, or w it hin t he inguinal canal. Painf ul ilioinguinal
neuropat hies are not uncommon af t er low er abdominal surgery (e. g. ,
herniorrhaphy or appendect omy) [77, 320, 330] , and ent rapment of t he nerve as
it passes t hrough t he muscles of t he abdominal w all, medial t o t he ant erior
superior iliac spine, has been described[180] . Neuropat hy may occur af t er
pregnancy, likely due t o t he st ret ching of t he nerve[32, 305] . Low er abdominal
and inguinal pain and parest hesias in prof essional ice hockey players w ere f ound
t o be due t o mult iple t ears of t he ext ernal oblique muscle and aponeurosis
causing ilioinguinal nerve ent rapment [183] . Lesions of t his nerve cause t he
i l i oi ngui nal syndrome, w hich consist s of pain and sensory loss in t he inguinal
region. Mot or f indings are negligible.
Alt hough t he ilioinguinal and iliohypogast ric nerves t ypically lie out side t he
gynecologic f ield of operat ion, t hey may become suscept ible t o injury w hen t he
Pf annenst iel incision is ext ended beyond t he lat eral border of t he rect us
abdominis muscle, int o t he subst ance of t he int ernal oblique muscle[148] . The
sympt oms are at t ribut ed t o sut ure incorporat ion of t he nerve during f ascial
repair, direct nerve t rauma w it h subsequent neuroma f ormat ion, or neural
const rict ion as a result of t he normal scarring and healing processes. The
diagnost ic t riad f or ilioinguinal/ iliohypogast ric nerve post surgical ent rapment
syndrome consist s of t he f ollow ing[148] :
1. Sharp, burning pain emanat ing f rom t he incision sit e and radiat ing t o t he
suprapubic, labial, or t high areas
2. Parest hesia over t he appropriat e nerve dist ribut ion
3. Pain relief af t er inf ilt rat ion w it h a local anest het ic
The onset of sympt oms may be immediat e or may occur mont hs t o years af t er
t he off ending surgical procedure. The sympt oms are exacerbat ed as a result of
st ret ching, coughing, sneezing, and Valsalva and can be relieved w it h hip f lexion
or by adopt ing a st ooped post ure w hen ambulat ing[148] .
I n a st udy of 33 pat ient s w it h ilioinguinal and iliohypogast ric neuralgias, 29
(88%) of t hem had injuries f rom iat rogenic causes, and f our (12%) had injuries
caused by blunt t rauma[171] . I n t he 23 isolat ed ilioinguinal neuralgias, operat ion
associat ed w it h neuralgias in 13 (57%) w as a herniorrhaphy f ollow ed by f our
(17%) af t er an appendect omy and t hree (13%) af t er a hyst erect omy. Three
(13%) pat ient s had neuralgias result ing f rom blunt t rauma. Nine (90%) of 10
ilioinguinal-iliohypogast ric lesions w ere caused by iat rogenic causes, and 1
(10%) neuralgia result ed f rom blunt t rauma[171] .
The geni tof emoral nerve, a predominant ly sensory nerve, arises f rom t he f irst
and second lumbar segment s w it hin t he subst ance of t he psoas muscle. I t
t raverses t he psoas muscle and, near t he inguinal ligament , divides int o t w o
branches: ext ernal spermat ic (genit al branch) and lumboinguinal (f emoral
branch). The external spermati c (geni tal ) branch (mainly L1) ent ers t he deep
inguinal ring, t raverses t he inguinal canal, and ends in t he cremast er muscle and
skin of t he scrot um (or labia majoris) and adjacent medial t high. The
l umboi ngui nal (f emoral ) branch (mainly L2) passes behind t he inguinal ligament
lat eral t o t he f emoral art ery and supplies t he skin of t he upper t high over t he
f emoral t riangle.
I njury t o t his nerve may occur in t he lumbar plexus, w it hin t he abdomen, or in t he

f emoral or inguinal region [77, 227, 320] (e. g. , af t er inguinal herniorrhaphy,
appendect omy, cesarean sect ion, hyst erect omy, vasect omy, blunt abdominal
t rauma, and even due t o w earing t ight jeans[233] ). Post operat ive injury t o t his
nerve is most likely t o occur during t he removal of a large pelvic mass adherent
t o t he sidew all or w hen biopsy or removal of t he ext ernal iliac lymph nodes is
perf ormed[ 148] . I njury causes pain (genit of emoral neuralgia) and sensory loss in
t he area of t he cut aneous supply of t he nerve. The cremast eric ref lex, w hich is
subserved by t his nerve, may be lost on t he side of t he nerve lesion.
FI G URE 2-10 The f emoral nerve.
Femoral Nerve (L2–L4)

Anatomy
The f emoral nerve, a mixed nerve, (Fig. 2-10) arises w it hin t he subst ance of t he
psoas muscle f rom t he post erior rami of t he second, t hird, and f ourt h lumbar
segment s. The nerve runs in t he groove bet w een t he psoas and iliacus muscles
(f lexors of t he t high, bot h of w hich it supplies) and descends beneat h t he inguinal
ligament (lat eral t o
t he f emoral art ery) t o ent er t he t high. Just dist al t o t he inguinal ligament w it hin
t he f emoral t riangle, it separat es int o t he ant erior and post erior divisions. The
anteri or di vi si on divides almost immediat ely int o a muscul ar branch (t o t he
sart orius muscle, a f lexor, and evert or of t he t high) and a sensory branch, t he
ant erior f emoral cut aneous nerve t hat supplies t he skin of t he ant erior and
medial aspect s of t he t high. The ant erior cut aneous branch f urt her divides int o
t he i ntermedi ate f emoral cutaneous nerve and t he medi al f emoral cutaneous
nerve. The medial f emoral cut aneous nerve has an ant erior branch t hat
innervat es t he ant eromedial t high and a post erior branch t hat innervat es t he
medial aspect of t he leg just below t he knee. The posteri or di vi si on of t he
f emoral nerve immediat ely divides int o t he sensory saphenous nerve and
muscul ar branches. The muscular branches of t he post erior division of t he
f emoral nerve supply t he f ollow ing muscles:
1. Pecti neus muscl e (L2–L3), an adduct or, f lexor, and evert or of t he t high.
2. Q uadri ceps f emori s muscl e (L2–L4), an ext ensor of t he leg. I t is t est ed by
having t he pat ient ext end t he leg against resist ance w it h t he ext remit y f lexed
at t he hip and knee. This muscle is also, part icularly t hrough t he rect us
f emoris, an ext ensor of t he t high. The t endon of t his muscle subserves t he
pat ellar ref lex.
The saphenous nerve descends t o t he knee in t he adduct or (Hunt er's) canal,

accompanied by t he f emoral art ery, and becomes cut aneous bet w een t he
t endons of t he sart orius and gracilis muscles. I t t hen joins t he great saphenous
vein and proceeds t o t he medial aspect of t he leg. I t supplies t he skin over t he
medial aspect of t he low er leg as f ar as t he medial malleolus.
Nerve Lesions
The most common cause of f emoral neuropat hy is t rauma, usually
iat rogenic[ 168, 181] . Common iat rogenic causes include inguinal herniorrhaphy,
t ot al hip replacement , int raabdominal vascular or gynecologic operat ions, and,
less commonly, appendect omy, lumbar sympat hect omy, laparoscopic procedures
and inadvert ent sut uring of t he nerve during abdominal hyst erect omy [148, 168,
181, 300] . A proximal f emoral neuropat hy may occur w it h pelvic surgery (e. g. ,
hyst erect omy) ow ing t o t he direct pressure exert ed by t he ret ract or blades or by
an indirect compression of t he nerve by compression of t he adjacent psoas
muscle by t he t ip of a ret ract or blade; t he neuropat hy may be bilat eral[182] . I n
one st udy, improper placement of self -ret aining or f ixed ret ract ors w as t he most
common cause of f emoral nerve injury arising in associat ion w it h abdominal
surgical procedures[148] . Unilat eral or bilat eral f emoral neuropat hy may also
occur af t er surgery or childbirt h in t he lit hot omy posit ion, likely due t o t he
compression of t he nerve against t he inguinal ligament or t he excessive st ret ch
of t he nerve by abduct ion and ext ernal rot at ion of t he t highs[9] . O t her causes of
f emoral neuropat hy w hile t he pat ient is in t he lit hot omy posit ion (e. g. , f or normal
delivery, vaginal hyst erect omy, or laparoscopy) include an iliopsoas or
ret roperit oneal hemat oma, especially in pat ient s w it h a bleeding diat hesis[366] ;
compression by t he f et al head, especially af t er a diff icult delivery or t he use of
f orceps[ 87] ; or ischemia, especially w it h a hist ory of int raoperat ive
hypot ension[ 5] . I n pat ient s undergoing vaginal surgery, maximal compression of
t he f emoral nerve and subsequent t ract ion-induced f emoral neuropat hy occur
w hen pat ient s are posit ioned in lit hot omy w it h excessive hip f lexion, hip
abduct ion, and ext ernal hip rot at ion, result ing in an 80- t o 90-degree ext reme
angulat ion of t he f emoral nerve beneat h t he unyielding inguinal ligament and
subsequent compression injury[148] . Aw areness of w hat const it ut es proper
lit hot omy posit ioning preoperat ively, and assurance t hat pat ient s are
appropriat ely posit ioned bef ore init iat ing t he procedure, w ill serve t o signif icant ly
reduce t he risk of bot h sciat ic nerve injury (see subsequent t ext ) and f emoral
nerve injury int raoperat ively[148] .
Femoral neuropat hy may also f ollow renal t ransplant at ion w it h possible
pat hophysiology including direct nerve compression and nerve ischemia[295] . A
pseudoaneurysm of t he prof unda f emoral art ery, f ormed af t er cardiac
cat het erizat ion or percut aneous t ransluminal coronary angioplast y, may cause
f emoral nerve compression[153] . Femoral nerve damage may also occur in t he
course of renal t ransplant at ion ow ing t o hemat oma at t he operat ive sit e[306] .
I liopsoas hemorrhage due t o ant icoagulat ion or hemophilia may damage t he
f emoral nerve and is associat ed w it h deep loin, back, and groin pain as w ell as
neuralgic pain in a f emoral cut aneous dist ribut ion[181] . Delayed f emoral
neuropat hy may also occur af t er inguinal radiat ion (usually developing 12 t o 16
mont hs af t er t reat ment ) and is associat ed w it h a palpable mass of dense scar in
t he groin[184] . I n int ravenous drug abusers, iliopsoas inf arct ion and acut e
f emoral neuropat hy may occur; t his f emoral involvement may be due t o ischemia,
inf lammat ion, or compression of t he nerve along it s course t hrough t he iliopsoas
muscle[ 159] .
Femoral nerve injury may also be due t o penet rat ing gunshot and st ab w ounds,
blunt injuries, lacerat ions, f emoral art ery cannulat ion, and st ret ch
or cont usion injuries associat ed w it h pelvic f ract ures[168, 181] . Acut e st ret ch
injuries may occur in gymnast s or dancers perf orming hyperext ension hip
exercises[ 215] . Tumors, including neurof ibromas, schw annomas, sarcomas,
ganglion cyst s, leiomyosarcoma, met ast ases, and abscesses may also injure t he
nerve[ 168] . I schemic neuropat hy of t he f emoral nerve may occur in pat ient s w it h
diabet es. A localized hypert rophic mononeuropat hy of t he f emoral nerve w it h
progressive w eakness and at rophy of t he t high has also been described[333] .
A proximal lesion of t he f emoral nerve (e. g. , at t he lumbar plexus or w it hin t he
pelvis) result s in t he f ollow ing signs:
1. Atrophy. There is w ast ing of t he musculat ure of t he ant erior part of t he t high.
2. Motor si gns. There is w eakness or paralysis of hip f lexion (iliacus, psoas,
and rect us f emoris muscles) and an inabilit y t o ext end t he leg (quadriceps
f emoris). Wit h paralysis of t he sart orius muscle, lat eral t high rot at ion may be
impaired.
3. Sensory symptoms and si gns. Sensory loss, parest hesias, and, occasionally,
pain occur on t he ant eromedial t high and inner leg as f ar as t he ankle.
4. Ref l ex si gns. The pat ellar ref lex is depressed or absent .
Lesions at t he inguinal ligament result in similar f indings, but t high f lexion is

spared because of t he more proximal origin of t he f emoral nerve branches t o t he
iliacus and psoas muscles. A purely mot or syndrome (quadriceps at rophy and
paresis) may result f rom lesions w it hin t he f emoral t riangle t hat aff ect t he
post erior division of t he f emoral nerve dist al t o t he origin of t he saphenous
branch. For example, isolat ed quadriceps paresis and at rophy may be due t o
localized nerve injury in w eight lif t ers[40] , select ive at rophy of t he dist al port ion
of t he vast us lat eralis muscle f ollow ed by dist al branch neuropat hy due t o
st ret ching and compression of t he nerve during st renuous exercise[240] , and a
muscle biopsy caused dist al w ast ing of t he vast us lat eralis by injuring t he dist al
f emoral nerve[303] . Unilat eral or bilat eral ant erior f emoral cut aneous nerve
injury, clinically sparing f emoral branches t o t he saphenous nerve and quadriceps
muscles, may occur f ollow ing surgical dissect ion in t he f emoral t riangles w it h
f emoral art ery reconst ruct ive surgery[29] . This purely sensory syndrome
manif est s by ant erior-medial t high pain and numbness and may occur af t er
aort of emoral bypass graf t surgery and ot her t ypes of f emoral art ery
reconst ruct ive surgery. I solat ed medial f emoral cut aneous neuropat hy, result ing
in parest hesias and dysest hesias over t he ant eromedial t high, af t er penet rat ing
injury t o t he ant eromedial aspect of t he t high has been described[190] .
A purely sensory syndrome (pain, parest hesias, and sensory loss) may result
w hen t he saphenous nerve alone is damaged. The nerve may be ent rapped
proximally in t he thi gh by f ibrous bands or branches of f emoral vessels[226] .
I solat ed saphenous involvement may occur w it h f emoral t hrombect omy and
f emoral-poplit eal bypass surgery[4] . Schw annomas of t he nerve may develop in
t he t high[93] . Spont aneous saphenous neuralgia[194] may result f rom nerve
compromise in t he subsart orial canal w here t he nerve crosses t he f emoral art ery
superf icially and penet rat es t he roof of t he canal. Medial knee and leg pain
result , and t enderness over t he subsart orial canal is present . The saphenous
nerve may be damaged at t he knee af t er medial art hrot omy or art hroscopy, in
associat ion w it h coronary art ery bypass graf t surgery, and by lacerat ions[186] .
This nerve is most suscept ible t o injury w here it pierces t he aponeurot ic roof of
t he adduct or canal above t he knee. Surf ers w ho sit ast ride t heir boards and grip
t he boards bet w een t heir knees may develop nerve compression (surf er's
neuropathy)[ 99] . A meniscal cyst can compress t he nerve at t he knee[355] . I n all
t hese syndromes, t he only sign is a sensory dist urbance t hat aff ect s t he medial
side of t he low er leg.
Damage t o t he inf rapat ellar branch of t he saphenous nerve result s in numbness
and parest hesias in t he skin over t he pat ella (gonyal gi a parestheti ca)[ 201] .
When bending t he knee, occasional pins-and-needles sensat ions are produced.
G onyalgia parest het ica usually develops insidiously w it hout acut e t rauma and is
of t en accompanied by sharp pain below and lat eral t o t he knee. The inf rapat ellar
branch may be injured during art hroscopy or ot her knee operat ions, by
accident al t rauma, or by nerve compression[143] .
Obturator Nerve (L2–L4)

Anatomy
The obt urat or nerve, a mixed nerve, (Fig. 2-11) arises f rom t he ant erior primary
rami of t he second, t hird, and f ourt h lumbar segment s w it hin t he subst ance of
t he psoas muscle. The nerve courses along t he pelvis and ent ers t he obturator
canal . Wit hin t he obt urat or canal, it supplies t he obt urat or ext ernus muscle and
t hen divides int o t w o branches, t he ant erior and post erior branches, w hich
descend int o t he medial t high. The mixed
anteri or di vi si on supplies t he pect ineus, adduct or longus, and adduct or brevis

(adduct ors of t he t high), and t he gracilis (an int ernal rot at or of t he t high and
f lexor of t he knee) and ends in a sensory termi nal branch t hat supplies t he skin
over t he medial t high. The mot or posteri or di vi si on supplies t he obt urat or
ext ernus, adduct or magnus, and adduct or brevis muscles (adduct ors of t he
t high). The adduct or magnus may also be innervat ed by t he sciat ic nerve. Mot or
f unct ion subserved by t he obt urat or nerve is evaluat ed by having t he pat ient
adduct t he ext ended leg against resist ance.
FI G URE 2-11 The obt urat or nerve and t he lat eral f emoral cut aneous nerve.
Nerve Lesions
The obt urat or nerve may be damaged w it hin t he lumbar plexus, near t he
sacroiliac joint , on t he lat eral pelvic w all, or w it hin t he obt urat or canal. Nerve
damage may occur w it h obt urat or hernia, af t er cancer surgery in t he pelvis,
secondary t o iliopsoas hemorrhage, w it h pelvic f ract ures, w it h pelvic t rauma,
af t er pelvic surgery, af t er f emoral art ery procedures, af t er bilat eral t ot al knee
art hroplast y w it h prolonged t ourniquet use, and af t er hip surgery (e. g. , due t o
nerve t ract ion or encasement of t he nerve by a spur of met hylmet hacrylat e
cement )[ 211, 310] . From a gynecologic st andpoint , t he obt urat or nerve is most
f requent ly injured during ret roperit oneal surgery f or gynecologic malignancies or
endomet riosis[ 148] . The node-bearing t issues of t he obt urat or space obscure t he
locat ion of t he obt urat or nerve and predispose it t o injury. O bt urat or nerve injury
can also occur at t he t ime of paravaginal def ect repair, perf ormed t o address
sympt omat ic lat eral displacement cyst ocele[148] . Bilat eral obt urat or nerve
injuries may occur during urologic surgery ow ing t o prolonged hip f lexion,
result ing in t he st ret ching of each nerve at t he bony obt urat or f oramen[243] .
Prolonged or diff icult labor may cause neuropat hy by t he compression of t he
nerve bet w een t he f et al head and t he bony pelvic w all[350] . O t her et iologies of
neuropat hy include endomet riosis, obt urat or hernias, nerve sheat h t umors,
obt urat or nerve ganglion, met ast asis t o t he obt urat or canal, myosit is ossif icans,
and nerve ent rapment by t hickened f ascia overlying t he adduct or brevis muscle
described in at hlet es [45, 46, 220, 262, 289, 291, 310] . Pat ient s w it h obt urat or
neuropat hy complain of leg w eakness and cannot st abilize t he hip joint . Nerve
lesions result in w ast ing of t he musculat ure of t he inner aspect of t he t high,
paresis of adduct ion of t he t high, and a sensory dist urbance aff ect ing t he medial
aspect of t he t high.
O bt urat or mononeuropat hy in cancer pat ient s is rare, but it may be t he sole
present ing sign of new or recurrent pelvic t umor or may occur as a complicat ion
of t umor surgery [155, 268, 286] . Tumor sit es on pelvic comput ed t omography
scan t hat correlat e w it h obt urat or nerve compression or inf ilt rat ion include t he
post erolat eral w all of t he upper pelvis or midpelvis, t he ant erior w all of t he low er
pelvis, and t he ext ernal obt urat or and pect ineus muscles ext rinsic t o t he bony
pelvis[ 268] .
Lateral Femoral Cutaneous Nerve (L2–L3)

Anatomy
The lat eral f emoral cut aneous nerve, a purely sensory nerve, (Fig. 2-11) derives
f rom t he primary rami of t he second and t hird lumbar segment s w it hin t he
subst ance of t he psoas muscle. I t penet rat es t he psoas and crosses t he iliacus
muscle t o t he ant erior superior iliac spine. I t t hen passes medially t o t he spine
beneat h t he inguinal ligament and ent ers t he t high beneat h t he f ascia lat a. The
nerve runs dow nw ard and divides int o t w o branches: t he anteri or di vi si on, w hich
supplies t he skin of t he ant erior t high t o t he knee, and t he posteri or di vi si on,
w hich supplies t he skin of t he upper half of t he lat eral aspect of t he t high.
Nerve Lesions
The nerve is of t en damaged w it hin t he abdomen (e. g. , by iliopsoas hemorrhage)
or in t he inguinal region[154] . Prolonged sit t ing in t he lot us posit ion may cause a
lat eral f emoral cut aneous neuropat hy (a f orm of l otus neuropathy)[ 205] .
Compression or angulat ion of t he nerve by t he inguinal ligament near t he ant erior
superior iliac spine may result in acut e or subacut e pain and parest hesias along
an oval area on t he lat eral or ant erolat eral aspect of t he t high. These
parest hesias are associat ed w it h sensory loss in t he cut aneous dist ribut ion of
t he lat eral f emoral cut aneous nerve (meral gi a [ meros, t high; al gos, pain]
parestheti ca or Bernhardt-Roth syndrome) [228, 351, 361] . This sensory
syndrome occurs especially in obese individuals w ho w ear const rict ing garment s
(e. g. , corset s, carpent ers' belt s) and may be bilat eral. Meralgia parest het ica
has also been report ed f rom seat -belt t rauma; af t er long dist ance w alking or
cycling, iliac bone procurement f or graf t ing, abdominal hyst erect omy by a
suprapubic approach (t hought t o be due t o prolonged post procedure hip f lexion
t o relieve t he abdominal incisional pain); as a complicat ion of a groin f lap or
renal surgery; or w it h malignant t umor of t he psoas muscle [12, 22, 33, 151,
167] . Nerve injury at t he t ime of pelvic surgery may result f rom t he inappropriat e
placement of lat eral ret ract or blades associat ed w it h self -ret aining or f ixed
ret ract ors[ 148] .
Gluteal Nerves (L4–S2)

The glut eal nerves, purely mot or nerves (Fig. 2-12) include t he superior glut eal
(f rom rami L4–S1) and inf erior glut eal (f rom rami L5–S2) nerves, w hich supply
t he musculat ure of t he but t ocks. The superi or gl uteal nerve leaves t he pelvis by
w ay of t he great er sciat ic not ch above t he pirif ormis muscle (suprapi ri f orm
f oramen) t o supply t he glut eus medius (L4–Sl), glut eus minimus (L4–Sl), and
t ensor f asciae lat ae (L4–Sl) muscles, w hich are abduct ors and int ernal rot at ors
of t he t high. These muscles are especially import ant in maint aining t he horizont al
plane of t he pelvis during w alking. Lesions of t he superior glut eal nerve may
occur w it hin t he lumbosacral plexus, pelvis, great er sciat ic f oramen, or but t ock.
Et iologies of superior glut eal neuropat hy include hip surgery, pelvic or hip
t rauma, hip f ract ure or dislocat ion, iliac art ery aneurysm, f all on t he but t ock,
inject ion, and ent rapment of t he nerve bet w een t he t endinous edge of t he
pirif ormis muscle and t he ilium [2, 123, 259, 260, 335, 362] . O n w alking, t he
pelvis t ilt s t ow ard t he side of t he unaff ect ed raised leg (Trendel enburg's si gn).
There is paresis or paralysis of t high abduct ion and medial rot at ion. I solat ed
complet e paralysis of t he t ensor f asciae lat ae may develop secondary t o
int ramuscular inject ion[225] .
The i nf eri or gl uteal nerve leaves t he pelvis by w ay of t he great er sciat ic not ch
below t he pirif ormis muscle (i nf rapi ri f orm f oramen), at w hich point it is near t he
sciat ic nerve and t he post erior cut aneous nerve of t he t high. This nerve sends it s
branches t o t he glut eus maximus muscle (L5–S2), t he main hip ext ensor, w hich is
t est ed by having t he pat ient ext end t he t high against resist ance.
FI G URE 2-12 The sciat ic nerve proper, superior glut eal nerve, and inf erior
glut eal nerve.
The inf erior glut eal nerve may be injured w it hin t he lumbosacral plexus, pelvis,
great er sciat ic f oramen, or but t ock. Nerve palsy result s in paresis or paralysis of
hip ext ension, w hich is most not iceable w hen t he pat ient at t empt s t o climb st airs.
Posterior Femoral Cutaneous Nerve (S1–S3)

The post erior f emoral cut aneous nerve, a purely sensory nerve arises f rom t he
ant erior primary rami of t he f irst t hrough t he t hird sacral segment s. I t leaves t he
pelvis t hrough t he great er sciat ic not ch and descends int o t he but t ock deep int o
t he glut eus muscle. I t supplies t he skin of t he post erior t high and poplit eal f ossa.
Damage t o t his nerve (w hich may occur in t he sacral plexus, great er sciat ic
f oramen, or but t ock) result s in a sensory dist urbance in t he cut aneous area of
supply of t he nerve. Neuropat hy may be due t o inject ions, lacerat ions, f alls ont o
t he but t ocks, presacral t umors, and prolonged bicycle riding[14, 149] . Post erior
f emoral cut aneous neuralgia due t o a venous malf ormat ion consist s of at t acks of
pain in t he lat eral scrot um, post erolat eral perineum, and post erior t high t o t he
poplit eal f ossa[67] .
Pudendal Nerve (S1–S4)

The pudendal nerve originat es f rom t he ant erior rami of t he f irst t hrough t he
f ourt h sacral segment s. I t leaves t he pelvis t hrough t he great er sciat ic not ch
below t he pirif ormis muscle (i nf rapi ri f orm f oramen) and reaches t he perineum.
This mixed nerve
supplies mot or branches t o t he perineal muscles and ext ernal anal sphinct er, as
w ell as sensory branches t o t he skin of t he perineum, penis (or clit oris), scrot um
(or labia majus), and anus.
The pudendal nerve may be injured by but t ock inject ions, pelvic f ract ures, hip
surgery, and prolonged bicycle riding (pedal l er's peni s) [119, 134, 212] . Lesions
of t his nerve produce a sensory dist urbance in t he cut aneous area of supply of
t hese nerves, erect ile impot ence, and diff icult y w it h bladder and bow el cont rol.
I njury t o t he pudendal nerve at t he t ime of vaginal surgery usually occurs in
associat ion w it h sacrospinous ligament f ixat ion f or vaginal vault prolapse[148] .
As t he pudendal nerve exit s t he pelvis via t he great er sciat ic f oramen, it runs
direct ly behind t he lat eral one-t hird of t he sacrospinous ligament bef ore t urning
t o reent er t he pelvis t hrough t he lesser sciat ic f oramen. I t is at t his point t hat
t he surgeon can unknow ingly ent rap t he pudendal nerve w it hin t he sut ure used t o
secure t he apex of t he vagina t o t he ipsilat eral sacrospinous ligament .
I ncorporat ion of t he pudendal nerve w it hin t his sut ure w ill result in immediat e or
delayed post operat ive glut eal pain and associat ed perineal anest hesia or
parest hesia[ 148] . Mot or abnormalit ies are usually absent .
Sciatic Nerve (L4–S3) and Its Branches

Sciatic Nerve Proper
The sciat ic nerve, a mixed nerve (Fig. 2-12), t he largest in t he body, derives
f rom t he f ourt h and f if t h lumbar and t he f irst and second sacral spinal segment s.
I t emerges f rom t he sacral plexus and leaves t he pelvis t hrough t he great er
sciat ic f oramen below t he pirif ormis muscle (i nf rapi ri f orm f oramen). The nerve
t hen curves lat erally and dow nw ard beneat h t he glut eus maximus muscle; in t he
post erior aspect of t he t high, it innervat es t he semit endinosus (L4–S2),
semimembranosus (L4–S2), and biceps f emoris (L4–S2) muscles (i. e. , t he
hamst ring muscles, w hich are f lexors of t he knee joint ) and t he adduct or magnus
(L2–L4) muscle, an adduct or of t he t high (w hich is also supplied by t he obt urat or
nerve). The nerve proceeds dow nw ard in t he t high, and at t he apex of t he
poplit eal f ossa, it divides int o it s t w o t erminal branches, t he ti bi al (medial
poplit eal) nerve (L4–S3) and t he common peroneal (lat eral poplit eal) nerve (L4–
S2).
Tibial Nerve
The t ibial nerve (Fig. 2-13) crosses t he middle of t he poplit eal space and
courses dow n t he back of t he leg. I n t he poplit eal f ossa, it gives off t he medi al
sural cutaneous nerve. This branch supplies t he skin on t he calf and t hen joins
t he lat eral sural cut aneous nerve (a branch of t he common peroneal) at t he level
of t he Achilles t endon, f orming t he sural nerve. The sural nerve supplies t he skin
on t he lat eral heel and lat eral aspect of t he f oot and small t oe.
I n t he dist al poplit eal f ossa, t he t ibial nerve sends branches t o t he
gast rocnemius (S1–S2) and soleus (S1–S2) muscles, w hich are t he main plant ar
f lexors of t he f oot , and t o t he poplit eus and plant aris muscles. The nerve t hen
descends in a plane bet w een t he gast rocnemius and soleus muscles post eriorly
and t he t ibialis post erior ant eriorly. Here it gives off branches t o t he f ollow ing
t hree muscles:
1. Ti bi al i s posteri or (L4–L5), a plant ar f lexor and invert or of t he f oot . I t is

t est ed by having t he pat ient invert t he f oot against resist ance or w alk on t he
t oes. I nversion should be t est ed w it h t he f oot in complet e plant ar f lexion,
t hereby eliminat ing t he act ion of t he t ibialis ant erior.
2. Fl exor di gi torum l ongus (L5–S2), a plant ar f lexor of t he f oot and of all t he
t oes except t he large t oe. I t is t est ed by having t he pat ient f lex t he t oes
3. Fl exor hal l uci s l ongus (S1–S2), a plant ar f lexor of t he f oot and t hat of t he
t erminal phalanx of t he great t oe. I t is t est ed by having t he pat ient plant ar
f lex t he great t oe against resist ance.
The t ibial nerve t hen passes inf erior t o t he medial malleolus along w it h t he
t endons of t he t ibialis post erior, f lexor hallucis longus, and f lexor digit orum
longus muscles and t he post erior t ibial art ery and vein. At t his locat ion, t he
lancinat e ligament roof s over t hese st ruct ures t o f orm a f ibroosseous t unnel (t he
tarsal tunnel). Wit hin t he t unnel t he nerve divides int o t he medial plant ar, t he
lat eral plant ar, and t he medial calcaneal nerves[242] . The medi al pl antar nerve
(S1–S2) supplies t he skin of t he medial t w o-t hirds of t he sole of t he f oot and
innervat es t he abduct or hallucis, f lexor digit orum brevis, f lexor hallucis, and t he
f irst t w o lumbricals of t he f oot . The l ateral pl antar nerve (S1–S2) carries
sensat ion t o t he lat eral t hird of t he f oot and innervat es t he abduct or digit i minimi
pedis, f lexor digit i minimi, adduct or hallucis, int erossei, and t he t hird and f ourt h
lumbricals of t he f oot . The medi al cal caneal branch supplies t he skin of t he
medial aspect of t he heel.
Common Peroneal Nerve

The common peroneal nerve (Fig. 2-14) gives off t he l ateral sural cutaneous
nerve in t he poplit eal f ossa. This branch joins t he medial sural cut aneous nerve
(f rom t he t ibial nerve) t o f orm t he sural nerve. I n t he poplit eal f ossa t he common
peroneal also gives off t he l ateral cutaneous nerve of the cal f, w hich descends
along t he lat eral head of t he gast rocnemius muscle t o supply t he skin on t he
lat eral aspect of t he leg below t he knee. The common peroneal nerve t hen
rounds t he head of t he f ibula and ent ers t he subst ance of t he peroneus longus
muscle, w here it divides int o t w o branches: t he deep peroneal (ant erior t ibial)
nerve and t he superf icial peroneal nerve. The deep peroneal nerve gives mot or
branches t o t he f ollow ing f our muscles:
FI G URE 2-13 The nerve.

1. Ti bi al i s anteri or (L4–L5), a dorsif lexor and invert or of t he f oot . I t is t est ed
by having t he pat ient dorsif lex t he f oot against resist ance or w alk on t he
heels.
2. Extensor hal l uci s l ongus (L5–Sl), an ext ensor of t he great t oe and
dorsif lexor of t he f oot . I t is t est ed by having t he pat ient dorsif lex t he dist al
phalanx of t he big t oe against resist ance.
3. Extensor di gi torum l ongus (L5–Sl), an ext ensor of t he f our lat eral t oes and
dorsif lexor of t he f oot . I t is t est ed by having t he pat ient dorsif lex t he t oes
FI G URE 2-14 The peroneal.
4. Extensor di gi torum brevi s (L5–Sl), an ext ensor of t he large t oe and t hree

medial t oes. I t is t est ed by having t he pat ient dorsif lex t he proximal
phalanges of t he t oes against resist ance.
The t erminal branch of t he deep peroneal nerve passes under t he t endon of t he
ext ensor hallucis longus on t he dorsum of t he f oot and, af t er supplying t he
ext ensor digit orum brevis, innervat es t he skin on t he f irst int erosseous space
and t he adjacent skin of t he sides of t he f irst and second t oes.
The superf i ci al peroneal nerve supplies t he peroneus longus and brevis muscles
(L5–S1), w hich are plant ar f lexors and evert ors of t he f oot . These are t est ed by
having t he pat ient evert t he f oot against resist ance. The nerve t erminat es as a
sensory termi nal branch, w hich innervat es t he skin of t he lat eral dist al port ion of
t he low er leg and t he dorsum of t he f oot and t oes (except t he f irst int erosseous
space).
I n 20% t o 28% of individuals, t he lat eral part of t he ext ensor digit orum brevis
(w hich ext ends t o t he f ourt h and f if t h digit s) is supplied by an accessory deep
peroneal nerve [84, 127, 319] , w hich is a branch of t he superf icial peroneal
nerve. This branch reaches t he ext ensor digit orum brevis by w inding around t he
lat eral malleolus.
An anomaly of innervat ion involving t he proximal t ibial nerve, common peroneal
nerve, and sural nerve has been described[127, 249] . Nerve f ibers f rom t he t ibial
nerve crossed over t o join t he common peroneal nerve in t he poplit eal f ossa. I n
t his case, t he sural nerve w as f ound t o arise t ot ally f rom t he common peroneal
nerve. The pat ient (w ho had suff ered injury t o t he common peroneal nerve at t he
knee) had evidence of some act ivit y (on elect rophysiologic t est ing) in t he
peroneus longus muscle w it h ot herw ise complet e paralysis of all common
peroneal innervat ed muscles[127, 249] . Also, an al l ti bi al f oot has been
described in w hich t he t ibial nerve innervat ed t he t ibialis ant erior muscle along
w it h t he peroneal nerve, innervat ed t he ext ensor digit orum brevis muscle, and
co-innervat ed t he skin bet w een t he f irst and second t oes w it h t he deep peroneal
nerve[ 365] .
Nerve Lesions
Lesions of the Sciatic Nerve Proper
The sciat ic nerve is f requent ly damaged in t he sacral plexus, t he pelvis, t he
glut eal region, or at t he sciat ic not ch. Nerve injury may occur w it h f ract ure
dislocat ion of t he hip[101] , apophyseal avulsion f ract ure[315] , af t er pelvic cancer
or hip joint surgery (because of t ract ion or a project ing spur of
met hylmet hacrylat e [42, 94, 116, 367] ), w it h compression by a het erot opic
ossif icat ion[ 1] , inf ect ions (e. g. , herpes simplex or zost er), glut eal hemorrhage,
or af t er int ramuscular inject ion[176] . Wit h inject ion, mot or f ibers are more
suscept ible t han sensory f ibers, and t he peroneal division of t he sciat ic nerve is
more severely injured because of it s lat eral posit ion. I njury t o t he sciat ic nerve
may rarely occur at t he t ime of laparot omy and generally result s f rom sudden
and unexpect ed pelvic hemorrhage requiring t he placement of large mat t ress
sut ures deep w it hin t he lat eral pelvis t o cont rol t he bleeding[148] . Such an injury
has also been report ed in associat ion w it h t he lat erally ext ended endopelvic
resect ion t echnique, w hich is required at t he t ime of exent erat ive pelvic surgery.
I n pat ient s undergoing vaginal surgery, maximal t ension on t he sciat ic nerve and
subsequent t ract ion-induced sciat ic neuropat hy occur w hen pat ient s are
posit ioned in lit hot omy w it h hip f lexion and knee ext ension or w it h ext ernal hip
rot at ion and knee f lexion[148] .
I n general, sciat ic lesions t end t o aff ect t he peroneal division more t han t he t ibial
division in about 75% of cases[367] . Nerve t umors and compression by
aneurysms of t he iliac art ery[340] may also cause neuropat hy. Complet e sciat ic
neuropat hy is due t o rhabdomyolysis causing a glut eal compart ment syndrome in
a pat ient using int ravenous heroin[177] . Cyclic sciat ic pain and sensorimot or
changes may occur w it h sciat ic endomet riosis (catameni al sci ati ca) [39, 266,
283, 368] . Sciat ic neuropat hy at t he t ime of cardiac surgery is of t en due t o
low er-limb ischemia; pat ient s w it h sympt omat ic peripheral vascular disease w ho
have a balloon pump insert ed int o t he f emoral art ery or w ho develop f emoral
art ery occlusion are at great est risk f or t his complicat ion[210] . Lymphoma may
invade t he nerve[160] w hich may be compressed by varicot ic glut eal vessels[31,
198] .
The pi ri f ormi s syndrome is an ent rapment syndrome of t he sciat ic nerve as it
passes t hrough t he great er sciat ic not ch[3] . But t ock t enderness, leg pain
aggravat ed by int ernal rot at ion of t he f lexed limb, a limp, and sciat ica
reproduced on deep digit al palpat ion are t he main f eat ures of t his clinical
syndrome, w hich is commonly caused by pelvic or but t ock t rauma, pelvic
surgery, mass lesions, f ibrous bands, and pirif ormis muscle anomalies. O t her
et iologies include pressure by a w allet (credi t-card–wal l et sci ati ca)[ 195] or by
coins in a back pocket (car tol l neuropathy)[ 34] . The sciat ic nerve may also be
compressed in t he t high as a consequence of yoga (l otus f oot drop)[ 346] , injured
by compression against an underlying prominent lesser t rochant er[72] , or even
damaged because of t oilet seat ent rapment (toi l et seat sci ati c neuropathy) [138,
334, 342] . A w oman w it h prof ound bilat eral low er ext remit y w eakness and
sensory abnormalit y af t er f alling asleep in t he head-t o-knees yoga posit ion (also
called Paschi mottanasana) has also been described (anot her f orm of yoga
neuropathy)[ 348] . Similar cases have occurred w it h sciat ic compression w hile in
a druken st upor or as a complicat ion of hip surgery[348] .
We propose t hat t he pat hophysiology of t he lesion could be relat ed t o a st ret ch
injury, a proximal compression/ inf arct of t he nerve in t he glut eal region (dist al t o
t he sciat ic not ch), or a combinat ion of bot h.
High sciat ic lesions result in t he f ollow ing signs (high t high lesions may
select ively involve peroneal f ibers):
1. Def ormi ty. A f l ai l f oot is present because of paralysis of t he dorsif lexors and
plant ar f lexors of t he f oot . When t he leg is passively lif t ed, t he f oot is
plant ar f lexed and invert ed (f oot drop), but it also dorsif lexes loosely w hen
t he f oot is passively moved back and f ort h.
2. Atrophy. There is w ast ing of t he hamst rings and all t he muscles below t he
knee.
3. Motor si gns. There is paresis or paralysis of knee f lexion (hamst rings), f oot
eversion (peronei), f oot inversion (t ibialis ant erior), f oot dorsif lexion (t ibialis
ant erior and ant erior leg musculat ure), f oot plant ar f lexion (gast rocnemius
and soleus), t oe dorsif lexion (ext ensors of t he t oes), and t oe plant ar f lexion
(plant ar f lexors of t he t oes).
4. Ref l ex si gns. There is a decrease or absence of t he Achilles ref lex (S1–S2),
w hich is subserved by t he t ibial nerve.
5. Sensory si gns. There are sensory changes (parest hesias and sensory loss)
on t he out er aspect of t he leg and t he dorsum of t he f oot (common peroneal
dist ribut ion) and on t he sole and t he inner aspect of t he f oot (t ibial nerve).
The skin of t he medial leg as f ar as t he medial malleolus is spared because
it is innervat ed by t he saphenous nerve (a branch of t he f emoral nerve). The
pat ient of t en complains of pain in t he sensory dist ribut ion and may have
t enderness along t he
course of t he nerve, especially paravert ebrally, or in t he but t ock and

post erior t high. Test s t hat st ret ch t he sciat ic nerve (e. g. , Lasegue's t est ,
G ow er's t est ) accent uat e t his pain.
6. Trophi c changes. Loss of hair and changes in t he t oenails and skin t ext ure
may occur in t he dist al leg below t he knee.
As t he sciat ic nerve is composed of t w o nerve t runks, medial and lat eral, w hich
become t he t ibial and peroneal nerves, respect ively, part ial sciat ic lesions may
diff erent ially involve t hese t runks and t hereby cause misleading localizat ion
def icit s. Sciat ic neuropat hies can t heref ore be mist aken clinically f or more dist al
neuropat hies, especially common peroneal neuropat hies or, less of t en, t ibial
neuropat hies[ 325] .
The sciat ic nerve in t he t high may be injured by gunshot w ounds, f emur
f ract ures, lacerat ions, and cont usions[176] . Nerve compression in t he t high may
be due t o f ibrous bands and aneurysms; nerve t umors may also occur in t his
locat ion[ 257, 309] . The sciat ic nerve proper may also be damaged just above t he
apex of t he poplit eal space (e. g. , ow ing t o poplit eal f ossa aneurysm)[ 24] . The
f indings are t he same as t hose seen w it h a more proximal sciat ic lesion, except
t hat t he hamst ring muscles are spared.
Lesions of the Tibial Nerve

The t ibial nerve is most of t en damaged in t he poplit eal space, w it hin t he t arsal
t unnel, or w it hin t he f oot (abductor hal l uci s syndrome).
1. Lesi ons at the popl i teal f ossa. Lesions of t he t ibial nerve at t his locat ion
result in paresis or paralysis of plant ar f lexion and inversion of t he f oot ,
plant ar f lexion of t he t oes, and movement s of t he int rinsic muscles of t he
f oot . Sensory impairment is locat ed on t he sole and t he lat eral border of t he
f oot . Et iologies of proximal t ibial neuropat hy include Baker's cyst s, t rauma
(especially if associat ed w it h poplit eal f ossa hemorrhage), nerve t umors, and
ent rapment by t he t endinous arch of t he origin of t he soleus muscle or a
hypert rophic poplit eus muscle [69, 85, 114, 145, 192, 204, 336] . Tibial nerve
ent rapment by t he arch of origin of t he soleus muscle can be dist inguished
f rom t ibial nerve compression at t he ankle and S1 radiculopat hy by t he
presence of severe pain and t enderness and a posit ive Tinel's sign in t he
poplit eal f ossa[204] . I n a ret rospect ive st udy of 52 pat ient s w it h main t runk
t ibial neuropat hy, t rauma and ischemia w ere t he most f requent causes,
f ollow ed by t umors[89] .
2. Lesi ons wi thi n the tarsal tunnel. At t he proximal end of t he t arsal t unnel, t he
t runk of t he t ibial nerve may be compressed by any process t hat causes
narrow ing of t he t unnel [78, 118, 236] . Rarely, t he f irst sympt oms of t he
tarsal tunnel syndrome emerge af t er an acut e event (ischemic or t raumat ic)
proximal t o but not aff ect ing t he ankle (“decompensat ion” of a preexist ing
asympt omat ic t arsal t unnel syndrome)[ 17] . Because t he medial plant ar,
lat eral plant ar, and medial calcaneal nerves branch dist al t o t his locat ion,
t here are burning parest hesias in t he sole of t he f oot and sensory loss
aff ect ing t he skin of t he sole and medial heel. O ccasionally, t he plant ar
nerves may be compressed individually w it hin t he t arsal t unnel (e. g. , leading
t o medial plant ar nerve sympt oms and signs only). Et iologies of t he t arsal
t unnel syndrome include t rauma t o t he ankle (e. g. , f ract ure and dislocat ion),
ill-f it t ing f oot w ear, cast s, post t raumat ic f ibrosis, ganglia or cyst s, nerve
t umors, abnormal muscles (e. g. , abduct or hallucis or accessory f lexor
digit orum longus), and compression by t he adjacent f lexor ret inaculum and
art eriovenous complex of t he post erior t ibial art ery and veins [20, 136, 178,
284, 308, 332, 349, 360] .
Sensory sympt oms are usually precipit at ed by st anding or w alking or by
pressure applied at t he ankle behind and below t he medial malleolus (Tinel's
sign). Noct urnal pain is also quit e common (analogous t o carpal t unnel
syndrome), and pat ient s of t en at t ain relief by hanging t he involved leg out of
bed. Mot or def icit s are minimal, but at rophy and paresis are present on
examinat ion of t he int rinsic muscles of t he f oot .
3. Lesi ons wi thi n the f oot. The medial or lat eral plant ar nerves may be
damaged w it hin t he f oot . This damage result s in pain, parest hesias, and
sensory loss in t he dist ribut ion area of t he individual nerve (e. g. , t he medial
t w o-t hirds of t he sole of t he f oot in medial plant ar nerve lesions). There may
be localized t enderness over t he individual nerve and some int rinsic muscle
at rophy and paresis. The medi al pl antar nerve may be compressed by t he
calcaneonavicular ligament , w here t he nerve pierces t he abduct or hallucis
muscle, by a hypert rophic or f ibrous abduct or hallucis muscle, or by t endon
sheat h cyst s[234, 324] . The medial plant ar nerve may also be injured by
t rauma (e. g. , f oot f ract ures) or schw annomas. Tw o pat ient s have been
described w it h neuropat hic medial plant ar f oot pain and t ingling due t o
sci ati c nerve schw annoma in t he mid-t high[ 117] . Lateral pl antar neuropathy
may be caused by ankle injury, surgical scarring, or schw annoma [28, 128,
235] . The most common sit e of lat eral plant ar nerve injury is at t he passage
of t he nerve t hrough t he abduct or
t unnel at t he inst ep of t he f oot [235] . Rarely, isolat ed medial calcaneal nerve

compression (e. g. , by ganglia or f ascial ent rapment ) may occur, result ing in
heel pain[242] .
A plant ar digit al nerve may be compressed w here it courses dist ally bet w een t he
heads of t he adjacent met at arsal bones, or st ret ched w here it crosses t he deep
met at arsal ligament . Pain, usually in t he t hird met at arsal space, is t he result .
This pain is ref erred t o as Morton's metatarsal gi a. The digit al nerve on t he side
of t he large t oe may be compressed by ill-f it t ing shoes or by scars f ollow ing
bunion surgery (Jopl i n's neuroma) [11, 68, 213] .
Lesions of the Common Peroneal Nerve

1. Lesi ons at the f i bul ar head. The majorit y of peroneal palsies occur at t he
level of t he f ibular head, w here t he nerve is quit e superf icial and suscept ible
t o injury[157] . Alt hough t he nerve may be damaged by nerve inf arct , cast s,
ganglion, Baker's cyst , hemat oma, t umor, or leprosy, most lesions are
t raumat ic (lacerat ion, t ract ion, or compression) [157, 163, 169, 356] . I n one
st udy of 318 knee-level common peroneal nerve lesions, t here w ere 141
st ret ch/ cont usions w it hout f ract ure/ dislocat ions (44%), 39 lacerat ions (12%),
40 t umors (13%), 30 ent rapment s (9%), 22 st ret ch/ cont usions w it h
f ract ure/ dislocat ions (7%), 21 compressions (7%), 13 iat rogenic injuries
(4%), and 12 gunshot w ounds (4%)[ 170] . St ret ch-induced peroneal
neuropat hy at t he f ibular head may be due t o f orcef ul inversion and plant ar
f lexion of t he ankle w hile kicking a f oot ball (punter's pal sy)[ 193] .
Post operat ive peroneal palsies occur especially af t er operat ions perf ormed
in t he lat eral decubit us posit ion or w hen t he out er aspect of t he upper leg
rest s against a leg st rap or met al brace. The nerve may also be st ret ched by
f lexion of t he hip and knee w hile t he pat ient is in t he lit hot omy posit ion (e. g. ,
postpartum f oot drop) and is especially liable t o injury af t er t ot al knee
art hroplast y[ 269] . Compressive lesions of t he common peroneal nerve are
usually unilat eral, but bilat eral (of t en asymmet ric) lesions may develop in
pat ient s w ho are habit ual leg crossers, especially t hose w ho have just lost
considerable w eight , are emaciat ed (e. g. , anorexia nervosa) or bedridden, or
have sust ained nerve inf arct s secondary t o vasculit is[157, 356] .
Compression may also occur w it h chronic squat t ing and w it h prot ract ed
sit t ing in t he cross-legged posit ion (e. g. , strawberry pi ckers' f oot drop)[ 179,
293] or during yoga (yoga f oot drop)[ 66, 200] . Bilat eral peroneal palsy may
occur during nat ural childbirt h ow ing t o prolonged pressure exert ed by t he
pat ient 's palms direct ly over t he upper lat eral aspect of t he shins w hile
st rongly draw ing t he knees t ow ard her (pushi ng pal sy)[ 6] . Drop f oot , caused
by peroneal neuropat hy, may also occur during w eight reduct ion (sl i mmer's
paral ysi s)[ 311] . Ent rapment of t he peroneal nerve in t he f ibular t unnel
(f i bul ar tunnel syndrome) may occur w it h a band at t he origin of t he
peroneus longus muscle[206] .
Wit h lesions at t he f ibular head, t he deep branch of t he nerve is aff ect ed
more commonly t han t he w hole nerve[312, 325] , alt hough t he superf icial
branch alone may also be aff ect ed. Wit h common peroneal neuropat hies,
w eakness is usually more prominent in muscles supplied by t he deep
peroneal nerve t han in muscles supplied by t he superf icial peroneal nerve,
likely because of diff ering degrees of damage t o individual f ascicles w it hin
t he common peroneal nerve [161, 312, 325] . When bot h branches (deep and
superf icial) are aff ect ed, t here is paresis or paralysis of t oe and f oot
dorsif lexion and of f oot eversion. A variable sensory dist urbance aff ect s t he
ent ire dorsum of t he f oot and t oes and t he lat eral dist al port ion of t he low er
leg. When only t he deep branch of t he peroneal nerve is aff ect ed, a deep
peroneal nerve syndrome occurs (see subsequent sect ion).
I n some pat ient s w it h common peroneal neuropat hy, t he ext ensor hallucis
longus is t he most severely aff ect ed muscle, producing bi g toe drop rat her
t han f oot drop[329] . This is presumably due t o select ive damage of t he
f ascicle w it hin t he common peroneal nerve t hat cont ains t he mot or f ibers t hat
supply t he ext ensor hallucis muscle[325] .
2. The anteri or ti bi al (deep peroneal ) nerve syndrome. This nerve may be
injured in isolat ion at t he f ibular head or more dist ally in t he leg. Nerve injury
result s in a mot or def icit (paresis or paralysis of t oe and f oot dorsif lexion);
sensory def icit is limit ed t o t he w eb of skin locat ed bet w een t he f irst and
second t oes. I f an accessory (anomalous) deep peroneal nerve is present ,
t he ext ensor digit orum brevis muscle, or at least t he lat eral port ion of t his
muscle, is spared[84] . Et iologies of proximal nerve injury include
compressive masses (e. g. , ganglia, ost eochondromas, aneurysms), direct
t rauma (e. g. , f ibular f ract ures or surgery), t hrombosis of crural veins[30] ,
and occlusion of t he ant erior t ibial art ery.
I solat ed deep peroneal nerve injury may complicat e art hroscopic knee
surgery[ 98] . At t he level of t he knee joint , t he deep and superf icial peroneal
nerves are usually joined as t he common peroneal nerve. Because of t he
f ascicular st ruct ure, how ever, a part ial nerve injury can result in an isolat ed
injury t o deep peroneal f ibers[98] .
The deep peroneal nerve may also be compressed at t he ankle (anteri or
tarsal tunnel
syndrome)[ 357] . The ant erior t arsal t unnel syndrome is caused by ankle
f ract ures, dislocat ions, sprains, ill-f it t ing shoes, or ext reme ankle inversion
and is due t o dist al deep peroneal compression beneat h t he crural cruciat e
ligament [ 357] . This compression result s in paresis and at rophy of t he
ext ensor digit orum brevis muscle alone. The t erminal sensory branch t o t he
skin w eb bet w een t he f irst and second t oes may be aff ect ed by lesions at
t his locat ion. I at rogenic, isolat ed w eakness or paralysis of t he ext ensor
hallucis longus muscle is a common complicat ion of proximal t ibial and f ibular
ost eot omy; t he nerve supply t o t he ext ensor hallucis longus is at high risk f or
injury during t ibial ost eot omy because of t he proximit y of t he bone t o t he
mot or branches[174] . A dist al peroneal neuropat hy may occur because of
nerve injury during needle aspirat ion of t he ankle joint . The deep peroneal
sensory branch may be ent rapped in t he f oot dist al t o t he inf erior ext ensor
ret inaculum as t he nerve passes under t he t endon of t he ext ensor hallucis
brevis muscle; a Tinel's sign can be elicit ed by percussion of t he t endon, and
numbness and t ingling occur over t he f irst w eb space of t he f oot [252] .
3. The superf i ci al peroneal nerve syndrome. The superf icial peroneal nerve
may be aff ect ed in isolat ion by lesions at t he f ibular head or by lesions more
dist ally in t he leg. Paresis and at rophy of t he peronei (f oot eversion) and a
sensory dist urbance aff ect ing t he skin of t he lat eral dist al port ion of t he
low er leg and dorsum of t he f oot are present . The w eb of skin bet w een t he
f irst and second t oes is spared (t his is t he area of supply of t he deep
peroneal nerve). I f an accessory deep peroneal nerve is present , t he lat eral
part of t he ext ensor digit orum brevis muscle is paret ic and at rophic[84] . The
sensory port ion of t he superf icial peroneal nerve may be aff ect ed in isolat ion
(e. g. , w here it emerges f rom t he f ascia) ow ing t o inversion injury or
compression (e. g. , by w earing high lace-up boot s or skat es)[ 21] , causing a
purely sensory syndrome. Sympt oms may be accompanied by t enderness at
t he point of f ascial perf orat ion[318] . I at rogenic needle-induced neuropat hy of
t he dorsal medial int erosseous branch of t he peroneal nerve (during
venography w it h t he needle in t he dorsum of t he f oot ) has been
document ed[ 253] . Finally, an accessory deep peroneal neuropat hy may occur
in isolat ion (e. g. , by t rauma or ent rapment by a f ascial band), result ing in
isolat ed at rophy and paresis of t he ext ensor digit orum brevis[84, 275] .
TABLE 2-1 M ain Entrapment Neuropathies of the
Upper Limbs
Nerve Main Site of Com pression
Dorsal scapular Scalenus medius muscle
Suprascapular Suprascapular foramen
Axillary Quadrilateral space
Ligament of Struthers
Median Pronator teres
Carpal tunnel
Cubital tunnel
Ulnar
Guyon's canal
Spiral groove
Radial
Elbow
TABLE 2-2 M ain Entrapment Neuropathies of the

Low er Limbs
Nerve Main Site of Com pression
Abdominal wall
Ilioinguinal
Inguinal canal
Abdomen
Genitofemoral Femoral or inguinal canal
Psoas muscle
Femoral
Inguinal ligament
Pelvic wall
Obturator
Obturator canal
Lateral femoral cutaneous Inguinal ligament
Pelvis
Sciatic Gluteal region
Piriformis muscle
Popliteal fossa
Tibial Tarsal tunnel
Foot
Fibular head
Peroneal
Anterior tarsal tunnel
Lesions of the Sural Nerve

Sural neuropat hies present w it h pain or parest hesias over t he lat eral ankle and
border of t he f oot . The nerve may be damaged in t he poplit eal f ossa, t he calf ,
t he ankle, or t he f oot . Most sural neuropat hies are due t o lacerat ions, t rauma
associat ed w it h f ract ures, Achilles t endon reconst ruct ive surgery,
art hroscopy, and st ret ch injuries due t o sprains [120, 124, 255, 263] . The nerve
may be ent rapped by t endon sheat h cyst s, ganglia, Baker's cyst s, and scar
t issue [230, 255, 307] . Damage t o t he sural nerve ow ing t o ext ernal compression
(e. g. , t he upper edge of a ski boot or t ight elast ic st ockings) has been
inf requent ly report ed [124, 263, 301] .
The main ent rapment neuropat hies of t he upper and low er limbs are summarized
in Tables 2-1 and 2-2, respect ively.
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> Table of C ontents > C hapter 3 - C er vic al, B r ac hial, and Lum bos ac r al P lexi
Chapter 3
Cervical, Brachial, and Lumbosacral Plexi
Plexopat hies are usually more diff icult t o recognize t han lesions of individual
peripheral nerves (peripheral neuropat hies) or spinal root s (radiculopat hies)
because of t he complex anat omy of t he plexi. To localize a lesion accurat ely t o a
specif ic division of t he plexus, t he clinician must have mast ered not only t he
anat omic int ricacies of t hat division but also t he mot or and sensory supply of all
peripheral nerve component s supplied by t he division.
This chapt er review s t he anat omy of t he cervical, brachial, and lumbosacral plexi
and t he localizat ion of lesions w it hin t hese plexi.
The Cervical Plexus

Anatomy
The cervical plexus, w hich is f ormed by t he ant erior primary rami of C1–C4[ 51] ,
is sit uat ed behind t he st ernocleidomast oid muscle and in f ront of t he scalenus
medius and levat or scapulae muscles. I t consist s of a series of anast omot ic
loops sit uat ed near t he spinal accessory (cranial nerve XI ) and hypoglossal
(cranial nerve XI I ) nerves. The branches of t he cervical plexus may be divided
int o t hose t hat are predominant ly sensory and t hose t hat are predominant ly
mot or.
The cut aneous branches (Fig. 3-1), and t heir areas of sensory supply, include
t he f ollow ing nerves:
1. The greater occi pi tal nerve (C2) skin of t he post erior scalp
2. The l esser occi pi tal nerve (C2) skin of t he mast oid process and lat eral head
3. The great auri cul ar nerve (C2–C3) skin of t he low er cheek over t he
mandible, t he low er part of t he ext ernal ear, and t he upper neck below t he
ext ernal ear
4. The transverse col l i (cutaneous cervi cal nerves) (C2–C3) skin on much of
t he neck, especially t he ant erior neck
5. The supracl avi cul ar nerves (C3–C4) skin immediat ely above t he clavicle
I t should be not ed t hat t here is no dorsal root f rom C1; t heref ore, C1 is a purely
mot or root .
The muscular branches of t he cervical plexus (Fig. 3-2) include t he f ollow ing
nerves and branches:
1. The ansa hypogl ossi, w hich is a loop f ormed by f ibers f rom t he C1 root (t he
descending hypoglossal rami t hat course dow nw ard in company w it h t he
hypoglossal nerve proper) joining f ibers f rom t he C2 and C3 root s; t he f ibers
of t he ansa are dist ribut ed t o t he inf rahyoid muscles (i. e. , st ernohyoid,
omohyoid, st ernot hyroid, t hyrohyoid, and geniohyoid), w hich aid in head
f lexion.
2. The phreni c nerve (C3–C5), w hich innervat es t he diaphragm.
3. Branches to the mi ddl e scal ene and l evator scapul ae muscl es (C3–C4),
w hich are essent ially a lat eral f lexor of t he neck and a rot at or of t he
scapula, respect ively.
4. Branches to the accessory nerve (cranial nerve XI ), w hich supply t he
st ernocleidomast oid (C2) and t rapezius (C3–C4) muscles along w it h t he
accessory nerve proper.
Lesions of the Cervical Plexus

I njuries t o t he cervical plexus are inf requent , but any of it s branches can be
injured by penet rat ing w ounds, surgical injury (e. g. , carot id
endart erect omy or radical dissect ion of malignancy), or various mass lesions.
I nvolvement of t he cut aneous branches result s in alt ered sensat ion (e. g. ,
sensory loss, parest hesias, or pain) in t he dist ribut ion of t hese branches (e. g. ,
af t er a lesion of t he great auricular nerve, t here is loss of sensat ion over t he
mandible and low er ext ernal ear). When t he muscular branches of t he cervical
plexus are injured, t here is w eakness of t he inf rahyoid and scalene muscles
(ant erior and lat eral head f lexion), t he levat or scapulae (scapular rot at ion), and,
t o some degree, t he t rapezius (shoulder elevat ion) and st ernocleidomast oid
(head rot at ion and f lexion) muscles as w ell. The muscles aff ect ed and t he
degree of paresis depend on t he specif ic branch of t he cervical plexus t hat is
injured.
FI G URE 3-1 Sensory branches of t he cervical plexus
FI G URE 3-2 Mot or branches of t he cervical plexus
I ndividual branches of t he cervical plexus may be damaged. The greater

auri cul ar nerve is most commonly damaged during surgery t o t he neck or f ace
(e. g. , f ace lif t or parot id surgery) or during carot id endart erect omy [25, 104] .
Unilat eral or bilat eral great er auricular nerve damage may occur af t er hanging in
suicide at t empt s (numb ear i n resurrecti on)[ 6] . This nerve may also be injured
by t umors and af t er cardiac pacemaker insert ion[6] . The greater occi pi tal nerve
may be compressed or ent rapped in it s course t hrough t he muscles of t he
neck, especially t he semispinalis and t rapezius, or damaged by t rauma or

neurof ibroma. The l esser occi pi tal nerve may be injured during surgical
procedures involving t he post erior cervical t riangle or by lacerat ions.
I njuries t o t he phreni c nerve (C3–C5) deserve special considerat ion. Unilat eral
or bilat eral damage t o t he phrenic nerve is more of t en caused by a mediast inal
process t han by damage t o t he cervical plexus it self . Paralysis of t his nerve
result s in loss of diaphragmat ic movement on t he aff ect ed side. When unilat eral,
t his paralysis result s in lit t le disabilit y at rest , but dyspnea may occur w it h
exert ion. O n t he aff ect ed side, t he diaphragm f ails t o descend w it h inspirat ion
and may paradoxically be draw n upw ard. Bilat eral phrenic lesions may result in
prominent exert ional dyspnea and severe alveolar hypovent ilat ion w it h
hypocapnia. O ccasionally, t he phrenic nerve receives an anast omot ic branch
f rom t he subclavian nerve, in w hich case diaphragmat ic act ion may be normal
af t er a proximal phrenic lesion.
Unilat eral or bilat eral phrenic nerve paralysis may occur in isolat ion (idiopat hic
diaphragmat ic paralysis) or w it h more diff use mot or involvement as part of t he
Parsonage-Turner syndrome (neuralgic amyot rophy) [9, 74, 124] . The phrenic
nerve may also be damaged during operat ions in t he neck or chest (e. g. , open
heart surgery) or be compressed by aort ic aneurysms, int rat horacic neoplasms,
or enlarged mediast inal nodes [41, 55, 87, 115, 140] . The nerve may be injured in
t he neck during subclavian vein or int ernal jugular vein cat het erizat ion or as a
complicat ion of an indw elling cent ral venous cat het er [4, 100] .
Neck met ast ases, usually f rom breast cancer, may involve t he phrenic nerve
along w it h t he sympat het ic chain and recurrent laryngeal nerve, result ing in
phrenic palsy associat ed w it h an ipsilat eral Horner syndrome (miosis, pt osis)
and ipsilat eral vocal cord paralysis (Payne syndrome)[ 96] . Phrenic nerve injury
(unilat eral or bilat eral) may complicat e coronary art ery bypass surgery, perhaps
induced by hypot hermia, nerve st ret ch, or int ernal mammary art ery dissect ion or
harvest ing [12, 26, 76, 129] . During liver t ransplant at ion, t he phrenic nerve may be
t raumat ized w hen it is inadvert ent ly clamped along w it h t he inf erior vena
cava[ 12] . O t her causes of phrenic neuropat hy include amyot rophic lat eral
sclerosis, diabet es mellit us, mediast inal radiat ion t herapy, sarcoidosis,
t uberculosis, herpes zost er, Lyme disease, crit ical illness polyneuropat hy,
chronic inf lammat ory demyelinat ing polyradiculoneuropat hy (CI DP), and G uillain-
Barré syndrome [12, 27, 56, 110, 113, 138] .
The Brachial Plexus

Anatomy
The brachial plexus (Fig. 3-3) is f ormed f rom t he ant erior primary rami of t he
segment s C4, C5, C6, C7, C8, and T1[51] . The plexus is approximat ely 15 cm
long in adult s and ext ends f rom t he spinal column t o t he axilla. I t is divided int o
f ive major component s (in a proximal t o dist al direct ion): root s, t runks, divisions,
cords, and branches (t he mnemonic Robert Tayl or Dri nks Col d Beer serves as a
means of remembering t he names and order of t hese component s).
The f if t h and sixt h cervical root s course dow nw ard bet w een t he scalenus medius
and ant erior muscles and unit e t o f orm t he upper trunk of t he plexus. The
sevent h cervical root also inclines dow nw ard bet w een t he scaleni and, at t he
lat eral border of t he scalenus ant erior, emerges as t he mi ddl e trunk of t he
plexus. The eight h cervical and f irst t horacic spinal root s unit e behind a f ascial
sheet (Sibson's f ascia) and beneat h t he subclavian art ery f rom t he l ower trunk of
t he plexus.
The t hree t runks t raverse t he supraclavicular f ossa prot ect ed by t he cervical and
scalene musculat ure t hrough most of t heir course. Lat eral t o t he f irst rib, w here
t he t hree t runks are locat ed behind t he axillary art ery, t hey separat e int o three
anteri or and three posteri or di vi si ons. The t hree post erior divisions unit e behind
t he axillary art ery t o f orm t he posteri or cord. The ant erior divisions of t he upper
and middle t runks (C5–C7) unit e t o f orm t he l ateral cord, w hereas t he ant erior
division of t he low er t runk (C8–T1) f orms t he medi al cord. The cords pass
t hrough t he space f ormed by t he f irst rib and clavicle (thoraci c outl et) and t hen
give off t he major t erminal branches (peripheral nerves).
The major branches of t he brachial plexus and t he sit e of origin of t hese
branches are as f ollow s.
Branches Originating from the Spinal Roots

The dist ribut ion of t hese individual nerves is given in Chapt er 2. The l ong
thoraci c nerve arises direct ly f rom C5–C7 root s and descends vert ically behind
t he plexus t o innervat e t he serrat us ant erior muscle. The nerve to the subcl avi an
muscl e arises f rom t he C5 and C6 root s and t ravels ant erior t o t he plexus t o
innervat e t he subclavian muscle. The dorsal scapul ar nerve arises f rom t he C4
and C5 root s and innervat es t he levat or scapulae and rhomboid muscles.
FI G URE 3-3 The brachial plexus
Branch Originating from the Trunk of the Brachial

Plexus
The suprascapul ar nerve (C5–C6) arises f rom t he upper t runk near it s origin and
innervat es t he supraspinat us and inf raspinat us muscles.
Branch Originating from the Divisions of the Brachial

Plexus
The anteri or thoraci c nerves (C5–T1) (also called t he pectoral nerves) consist of
t he l ateral anteri or thoraci c nerve (C5–C7), w hich arises f rom t he ant erior
divisions of t he upper and middle t runks of t he plexus, and t he medi al anteri or
thoraci c nerve (C8–T1), w hich is a branch of t he medial cord of t he plexus. They
supply t he pect oralis major and minor muscles.
Branches Originating from the Cords of the Brachial

Plexus
The dist ribut ion of t hese individual nerves is given in Chapt er 2. Branches of t he
lat eral cord consist of (a) t he muscul ocutaneous nerve (C5–C7) and (b) t he
l ateral head of the medi an nerve (C5–C7). Branches of t he medial cord consist
of (a) t he medi al anteri or thoraci c nerve (C8–T1), (b) t he medi al cutaneous
nerve of the arm (C8–T1), (c) t he medi al cutaneous nerve of the f orearm (C8–
T1), (d) t he ul nar nerve (C7–T1), and (e) t he medi an head of the medi an nerve
(C8–T1). Branches of t he post erior cord consist of (a) t he subscapul ar nerve
(C5–C7), (b) t he thoracodorsal nerve (C5–C8), (c) t he axi l l ary nerve (C5–C6),
and (d) t he radi al nerve (C5–C8).
There may be considerable anat omic variat ion of t he brachial plexus. I n t he
pref i xed pl exus, all t he component s are shif t ed up one segment , result ing in a
major cont ribut ion f rom t he f ourt h cervical nerve. I n t he postf i xed pl exus, all t he
component s are shif t ed dow n one segment , result ing in lit t le or no cont ribut ion t o
t he plexus f rom t he f if t h cervical nerve and a dist inct cont ribut ion f rom t he
second t horacic nerve. These “one-level” variat ions in innervat ion occur in 3% t o
5% of pat ient s and must be considered in any pat ient w ho does not f it t he usual
clinical present at ion of a brachial plexopat hy.
Lesions of the Brachial Plexus

Brachi al pl exopathi es, in general, are usually incomplet e and charact erized by
muscle paresis and at rophy, loss of muscle st ret ch ref lexes, sensory changes
(usually pat chy and incomplet e), and of t en, shoulder and arm pain (usually
accent uat ed by arm movement ). The most promi nent si gn of a brachi al
pl exopathy i s a cl i ni cal def i ci t that i nvol ves more than one spi nal or peri pheral
nerve.
Brachial plexopat hies are common and may present w it h a mult iplicit y of clinical
syndromes t hat vary w it h t he component of t he plexus involved and t he locat ion
of t he lesion. Trauma is t he most f requent cause of damage and may occur as a
penet rat ing or closed injury (t ract ion, avulsion, compression, or st ret ch) [28, 38] .
Traumat ic st ret ch injuries are f requent consequences of mot or vehicle accident s,
especially in circumst ances in w hich t he vict im is propelled f rom t he vehicle
(e. g. , mot orcycle, snow mobile, all-t errain vehicle, or boat ). G unshot w ounds,
lacerat ions, birt h t rauma, f ract ure–dislocat ions of t he shoulder, and ort hopaedic
shoulder surgeries are ot her common sit uat ions associat ed w it h brachial plexus
injury [5, 68, 69, 92, 120] . Brachial plexopat hy in birt h t rauma is most commonly
not ed in children present ing in t he vert ex posit ion, w here progression of t he
shoulder is blocked by t he symphysis, causing t ract ion of t he brachial plexus
(shoulder dyst ocia)[ 92] . The main risk f act or f or shoulder dyst ocia is
macrosomia, w hich occurs in mat ernal diabet es. Repet it ive arm use in baseball
pit chers may cause pain and numbness in t he arm likely because of a
plexopat hy[ 82] . Cert ain “t raumat ic” plexopat hies may occur w it h a delayed onset
(hours or w eeks) because of neurovascular injury, w it h subsequent expanding
hemat oma or pseudoaneurysm[99] . The usual precipit ant s are f ract ure–
dislocat ion of t he humerus, gunshot w ounds, and axillary art ery t rauma
associat ed w it h medical procedures (especially ort hopaedic procedures).
Brachial plexus damage has also been described af t er reduct ion
mammaplast y[ 7] , subclavian vein cat het erizat ion [64, 98] , t horacoscopic
sympat hect omy[ 78] , and t horacoscapular f usion in f acioscapulohumeral muscular
dyst rophy[ 139] .
I nf raclavicular brachial plexopat hy is a component of t he medi al brachi al f asci al
compartment syndrome, a pot ent ial complicat ion of percut aneous axillary vessel
punct ure during axillary angiography or axillary regional block [16, 122, 123] . This
syndrome consist s of pain, w eakness, and numbness during or f ollow ing t he
percut aneous procedure and involves t he inf raclavicular brachial plexus, most
of t en t he median nerve alone, f ollow ed by combinat ions of median, ulnar, radial,
and musculocut aneous nerve involvement . The syndrome is of t en caused by
hemat oma f ormat ion w it hin t he medial f ascial brachial compart ment and requires
urgent surgery.
The brachial plexus is probably t he most suscept ible of all nerve groups t o
damage f rom poor posit ioning during anest hesia (posit ioning t rauma), perhaps
because of it s long mobile course and proximit y t o bony st ruct ures[24] . St ret ch
of nerve f ibers, rat her t han compression, is t he chief cause of injury[24] . Usually,
t hese plexopat hies present w it h painless mot or def icit s, especially aff ect ing t he
C5–C7 levels[15] . Upper plexus lesions occur w it h f ull arm abduct ion, w hereas
low er plexus lesions occur primarily w hen t he arm is close t o t he side. Abnormal
arm posit ioning during alcohol int oxicat ion or coma may also damage t he
plexus[ 108] .
O t her causes of brachial plexopat hy include serum- and vaccine-induced lesions,
radiat ion injuries, inf ect ions and t oxic causes, mass lesions (e. g. , neoplasms and
hemorrhage f rom ant icoagulant s), syst emic lupus eryt hemat osus, heroin
addict ion, CI DP, and heredit ary disorders [11, 17, 90, 102] . A brachial plexopat hy
(probably immune mediat ed) has been described secondary t o bot ulinum t oxin
inject ion f or t ort icollis [45, 116] , f ollow ing int ra-art erial administ rat ion of cisplat in
chemot herapy[ 61] , and af t er int ravenous high-dose cyt arabine
chemot herapy[ 106] .
Inheri ted brachi al pl exus neuropathy has also been described (aut osomal
dominant inherit ance), w it h recurrent episodes of brachial plexus neuropat hy
occurring in mult iple f amily members [14, 19, 29, 43, 60, 136] . The brachial plexus
may also be involved in approximat ely 10% of pat ient s w it h heredi tary
neuropathy wi th l i abi l i ty to pressure pal si es, also an aut osomal dominant
condit ion, and recurrent brachial plexopat hy may be t he only sympt om of
ent rapment in some f amilies [8, 18, 89, 93, 135, 136] . A variant of mult if ocal mot or
neuropat hy in t he brachial plexus may present w it h progressive arm w eakness
and t onic hand spasm[125] .
Brachial plexopat hy (radiculoplexopat hy) may occur as a complicat ion of
coronary art ery bypass graf t surgery or cardiac valve replacement and usually
aff ect s t he low er t runk or medial cord f ibers [53, 76, 81] . Because t here is a
correlat ion bet w een t he sit e of jugular vein cannulat ion and t he aff ect ed side in
most cases, needle t rauma is t hought t o play a role[76] . Wit h open heart surgery
t hrough median st ernot omy, bilat eral (alt hough asymmet ric) brachial plexopat hies
may occur, w it h pain being a prominent f eat ure[48] . Brachial plexus injury may
also f ollow liver t ransplant at ion[66] .
Primary t umors of t he brachial plexus (i. e. , schw annomas, neurilemomas, and
neurinomas) are rare and usually present w it h a slow ly grow ing sw elling in t he
supraclavicular f ossa or axilla, w it h lit t le mot or or sensory disabilit ies (except
occasional pain) not ed [10, 69, 83, 94, 107] . I n a series of 25 pat ient s w it h primary
brachial plexus t umors, t he present ing signs and sympt oms included
palpable mass (60%), numbness or parest hesias (44%), radiat ing pain (44%),
local pain (16%), and w eakness (12%)[ 10] . Localized hypert rophic neuropat hy of
t he plexus, w it h progressive upper limb neurologic def icit s, may rarely
occur[ 109] . The plexus is more of t en aff ect ed by met ast ases (most f requent ly
f rom breast cancer) or by direct inf ilt rat ion f rom neighboring neoplasm,
especially f rom carcinoma of t he upper lobe of t he lung (Pancoast tumor). Wit h
t he lat t er lesions, t he low er brachial plexus is init ially aff ect ed, result ing in pain
in t he ulnar side of t he hand, f orearm, and arm, f ollow ed by ot her sensory
sympt oms and t hen by mot or sympt oms and Horner syndrome.
Brachial plexus lesions may also occur mont hs t o years af t er radiot herapy,
usually f or breast cancer and Hodgkin's lymphomas [70, 71] . I t is of t en diff icult
t o dist inguish a plexopat hy due t o radiot herapy f rom t hat due t o recurrent
neoplasm or met ast ases. The clinical present at ion may help dist inguish t hese
t w o causes of plexopat hy[71] . Wit h met ast at ic disease, t he low er t runk (C8–T1)
is predominant ly or exclusively involved, severe pain is present at onset , and
Horner syndrome is common. Wit h radiat ion-induced plexopat hy, t he upper t runk
or ent ire plexus is predominant ly aff ect ed, parest hesias and w eakness are more
prominent t han pain at t he onset , and progressive lymphedema of t he arm is
more common. The numbness of t en involves t he lat eral aspect of t he arm, and
t here is w eakness of t he shoulder girdle muscles. Some clinicians, how ever,
have f ound no diff erence bet w een t he anat omic dist ribut ion of brachial plexus
involvement in pat ient s w it h neoplast ic plexopat hy and in t hose w it h radiat ion-
induced plexopat hy[50] . I n bot h groups, w eakness involved t he muscles
innervat ed predominant ly by t he low er t runk or t he ent ire plexus. Pat ient s w it h
neoplast ic plexopat hy had a (a) higher f requency of pain as t he init ial and
predominant sympt om, (b) short er durat ion of sympt oms bef ore diagnosis, and
(c) higher incidence of Horner syndrome t han pat ient s w it h radiat ion-induced
plexopat hy[ 50] . I n a st udy of radiat ion plexopat hy in breast cancer, t he ent ire
plexus w as aff ect ed in 50%, t he upper t runk in 18%, t he low er t runk in 4%, w it h
assessment of level not clinically possible in 28%[ 91] . I n t hese pat ient s,
sympt oms of t en st art ed during or immediat ely af t er radiat ion t herapy, w it h
numbness or parest hesias and pain being t he most prominent sympt oms. I n
anot her st udy of radiat ion plexopat hy in pat ient s w it h breast cancer, how ever,
t he lat ency t o onset of sympt oms w as 1 mont h t o 15 years, w it h mot or def icit s,
pain, and parest hesias as t he init ial sympt oms at present at ion[35] . An acut e
ischemic brachial plexopat hy f rom occlusion of t he subclavian art ery may occur
as a lat e complicat ion of radiat ion t herapy[44] . This disorder is predominant ly
mot or, sudden in onset , and painless, w it h parest hesias of t en f elt in t he f orearm
and hand. An acut e reversi bl e brachial plexopat hy has been report ed in some
pat ient s short ly af t er radiat ion t herapy f or breast cancer[103] . The sympt oms
generally occurred approximat ely 4 mont hs af t er radiat ion t herapy and w ere
charact erized by mild shoulder pain and arm parest hesias w it h severe but
reversible arm w eakness. Radiat ion-induced malignant and at ypical peripheral
nerve sheat h t umors may also aff ect t he brachial plexus and may be diff icult t o
diff erent iat e f rom t umor recurrence or radiat ion plexopat hy[39] . Finally, a
paraneopl asti c brachial plexopat hy may occur in pat ient s w it h Hodgkin's disease,
especially f ollow ing radiat ion t herapy [73, 97] .
Neuralgic Amyotrophy
Parsonage-Turner syndrome [ 34] is a disorder charact erized by acut e, severe
pain locat ed in t he shoulder and radiat ing int o t he arm, neck, and back. To
prevent pain, movement of t he arm is avoided and it is held in a posit ion of
f lexion at t he elbow and adduct ion at t he shoulder (t he f l exi on–adducti on si gn)
[ 128] . The pain is f ollow ed w it hin several hours t o days by paresis of t he
shoulder and, predominant ly, proximal arm musculat ure. Sensory loss can occur
but is generally not marked. The muscles innervat ed by t he axillary,
suprascapular, radial, musculocut aneous, and long t horacic nerves are most
commonly aff ect ed. Unilat eral or bilat eral phrenic nerve paralysis may occur
[ 74] . The pain usually disappears w it hin several days and bilat eral (usually
asymmet ric) involvement may occur. The process is t hought t o be a brachial
plexit is or mult iple mononeurit is and is usually idiopat hic, but may f ollow viral
illness, immunizat ions, surgery, or childbirt h [77, 84, 85] . Heredi tary neural gi c
amyotrophy is an aut osomal dominant disorder w it h recurrent , episodic, painf ul,
brachial neuropat hy somet imes associat ed w it h charact erist ic f eat ures such as
hypot elorism, short st at ure, and clef t palat e[60] .
Total Plexus Paralysis

Tot al plexus paralysis is a rare syndrome t hat is usually due t o severe t rauma
(usually a f all f rom a moving vehicle) and is charact erized by t he f ollow ing signs:
Motor Si gns. The ent ire arm is paralyzed and hangs limp at t he pat ient 's
side. All t he arm's musculat ure may undergo rapid at rophy.
Sensory Si gns. There is usually complet e anest hesia of t he arm dist al t o a

line ext ending obliquely f rom t he t ip of t he shoulder dow n t o t he medial arm
half w ay t o t he elbow.
Ref l ex Si gns. The ent ire upper ext remit y is aref lexic.
Upper Plexus Paralysis (Erb-Duchenne Type)
Upper plexus paralysis (Erb-Duchenne t ype) is a lesion t hat result s f rom damage
t o t he f if t h and sixt h cervical root s or t he upper t runk of t he brachial plexus. I t is
a common def icit and is usually due t o f orcef ul (t raumat ic) separat ion of t he
head and shoulder but may also be due t o pressure on t he shoulder (e. g. ,
knapsack paralysis, rucksack paralysis, cadet palsy, or pack paralysis), f irearm
recoil[ 127] , birt h injury [5, 33, 95] , and idiopat hic plexit is (“neuralgic amyot rophy”
or Parsonage-Turner syndrome). Sudden f orcef ul depression of t he shoulder
during cont act sport s, especially f oot ball, may cause a t ransient episode of
abrupt , int ense burning dysest hesia and anest hesia involving one ent ire upper
ext remit y, usually accompanied by generalized limb w eakness (burners or
sti ngers) [37, 52, 131] . The sympt oms usually resolve in minut es w it hout
neurologic residual. Alt hough sympt oms in t his condit ion involve t he ent ire limb,
f indings are most prominent in t he dist ribut ion of t he upper t runk of t he plexus
[ 52, 131] . O t her sport s report ed t o cause t his syndrome include w rest ling,
hockey, basket ball, boxing, and w eight lif t ing[37] .
The upper plexus syndrome consist s of t he f ollow ing signs:
Motor Si gns. The muscles supplied by t he C5–C6 root s are paralyzed or

paret ic and at rophic. These include t he delt oid, biceps, brachioradialis, and
brachialis, and occasionally, t he supraspinat us, inf raspinat us, and
subscapularis as w ell. The posit ion of t he limb is charact erist ic—t he limb is
int ernally rot at ed and adduct ed and t he f orearm is ext ended and pronat ed,
t he palm t heref ore f acing out and backw ard. This is t he so-called
policeman's t ip or port er's t ip posit ion. Shoulder abduct ion (delt oid and
supraspinat us), elbow f lexion (biceps, brachioradialis, brachialis), ext ernal
rot at ion of t he arm (inf raspinat us), and f orearm supinat ion (biceps) are
impaired. Very proximal lesions may also cause w eakness of t he rhomboids,
levat or scapulae, serrat us ant erior, and scalene muscles.
I t has been not ed t hat in some cases of obst et ric brachial plexopat hy, injured
phrenic nerve or C3–C5 root s may sprout int o t he adjacent injured upper and
middle t runks of t he brachial plexus. This aberrant regenerat ion produces co-
cont ract ion of t he diaphragm and proximal limb muscles, result ing in t he
phenomenon ref erred t o as respi ratory synki nesi s or t he breathi ng arm[ 40] .
This reinnervat ion may not be limit ed t o t he upper cervical root s because
cases have been described of respirat ory synkinesis select ively aff ect ing
int rinsic hand muscles (breathi ng hand)[ 40] . I t is proposed t hat aberrant
regenerat ion f rom upper t horacic root s and t heir int ercost al nerves may
produce respirat ory synkinesis, result ing in t he “breat hing hand”[40] .
Sensory Si gns. Sensat ion is usually int act , but t here may be some sensory
loss over t he out er surf ace of t he upper arm, especially over t he delt oid
muscle.
Ref l ex Si gns. The biceps and brachioradialis ref lexes are depressed or
absent .
M iddle Plexus Paralysis

Lesions of t he middle t runk or t he corresponding individual ant erior primary
ramus of t he sevent h cervical root are rare but occur occasionally w it h t rauma.
The sevent h cervical f ibers t o t he radial nerve are primarily involved, and
t heref ore t he ext ensors of t he f orearm, hand, and f ingers are paret ic (including
t he t riceps, anconeus, ext ensor carpi radialis and ulnaris, ext ensor digit orum,
ext ensor digit i minimi, ext ensor pollicis longus and brevis, abduct or pollicis
longus, and ext ensor indicis). Forearm f lexion is spared because t he
brachioradialis and brachialis are innervat ed predominant ly by t he f if t h and sixt h
cervical segment s. The t riceps ref lex may be depressed or absent , and a
sensory def ect , alt hough inconsist ent and of t en pat chy, may occur over t he
ext ensor surf ace of t he f orearm and t he radial aspect of t he dorsum of t he hand.
Low er Plexus Paralysis (Dejerine-Klumpke Type)

The low er t ype of brachial plexopat hy (Dejerine-Klumpke t ype) result s f rom
injury t o t he eight h cervical and f irst t horacic root s or t he low er t runk of t he
plexus. I t is usually t he result of t rauma, especially arm t ract ion in t he abduct ed
posit ion, but is also seen af t er surgical procedures and is associat ed w it h lung
t umors (e. g. , Pancoast t umor) or ot her mass lesions (e. g. , aneurysms of t he
aort ic arch). The low er plexus syndrome consist s of t he f ollow ing signs:
Motor Si gns. All t he musculat ure supplied by t he eight h cervical and f irst
t horacic root s are paret ic
and event ually at rophic. Theref ore, t here is w eakness of w rist and f inger
f lexion and w eakness of t he int rinsic hand muscles. O f t en, a claw hand
def ormit y is evident .
Sensory Si gns. Sensat ion may be eit her int act or lost on t he medial arm,
medial f orearm, and ulnar aspect of t he hand.
Ref l ex Si gns. The f inger f lexor ref lex (C8–T1) is depressed or absent .
Autonomi c Si gns. When t he f irst t horacic root is injured, t he sympat het ic
f ibers, dest ined f or t he superior cervical ganglion (and event ually t he eye,
upper lid, and f ace), are int errupt ed. Theref ore, an ipsilat eral Horner
syndrome (pt osis, miosis, and anhidrosis) result s.
Lesions of the Cords of the Brachial Plexus

Lesions of the Lateral Cord
Lat eral cord lesions are usually due t o surgical or local t rauma and result in
paresis of t he muscles innervat ed by t he musculocut aneous nerve and t he lat eral
head of t he median nerve. Theref ore, t here is paresis of t he biceps, brachialis,
and coracobrachialis (w hich cont rol elbow f lexion and f orearm supinat ion)
because of musculocut aneous nerve injury, as w ell as paresis of all muscles
innervat ed by t he median nerve except t he int rinsic hand muscles. As a result ,
t he f ollow ing muscles are w eak: pronat or t eres (f orearm pronat ion), f lexor carpi
radialis (radial w rist f lexion), palmaris longus (w rist f lexion), f lexor digit orum
superf icialis (middle phalangeal f lexion of t he second t hrough f ourt h digit s),
f lexor pollicis longus (f lexion of t he dist al phalanges of t he t humb), f lexor
digit orum prof undus I and I I (f lexion of t he dist al phalanges of t he second and
t hird f ingers), and pronat or quadrat us (f orearm pronat ion). The biceps ref lex is
depressed or absent . Sensory loss may occur on t he lat eral f orearm (t he area of
dist ribut ion of t he lat eral cut aneous nerve of t he f orearm, a branch of t he
musculocut aneous nerve).
Lesions of the M edial Cord

Lesions of t he medial cord of t he brachial plexus result in w eakness of t he
muscles innervat ed by t he ulnar nerve and t he medial head of t he median nerve
(t he median-innervat ed int rinsic hand muscles). The ulnar muscles involved are
t he f lexor carpi ulnaris (ulnar w rist f lexion), f lexor digit orum I I I and I V (f lexion of
t he t erminal digit s of t he f ourt h and f if t h f ingers), and all t he ulnar-innervat ed
small hand muscles. The median muscles involved are t he abduct or pollicis
brevis (abduct ion of t he met acarpal of t he t humb), opponens pollicis (opposit ion
of t he t humb), superf icial head of t he f lexor pollicis brevis (f lexion of t he
proximal phalanx of t he t humb), and t he f irst and second lumbricals. Wit h
proximal lesions of t he medial cord, t he medial ant erior t horacic nerve may be
injured, result ing in some paresis of t he low er st ernocost al port ion of t he
pect oralis major muscle and of t he pect oralis minor. The f inger f lexor ref lex is
decreased or absent . Because t he medial cut aneous nerves of t he arm and
f orearm are branches of t he medial cord, a sensory loss may be evident on t he
medial arm and f orearm.
Lesions of the Posterior Cord

Lesions of t he post erior cord result in disabilit y in t he f ields of dist ribut ion of t he
subscapular, t horacodorsal, axillary, and radial nerves. Subscapular nerve injury
result s in paresis of t he t eres major and subscapularis (int ernal rot at ors of t he
humerus), w hereas t horacodorsal nerve injury result s in lat issimus dorsi paresis.
Axillary injury manif est s as delt oid (arm abduct ion) and t eres minor (lat eral
rot at ion of t he shoulder joint ) paresis, as w ell as variable sensory loss in t he
dist ribut ion of t he lat eral cut aneous nerve of t he arm (skin of t he lat eral arm).
Radial injury result s in paresis of elbow ext ension, w rist ext ension, f orearm
supinat ion, and f inger ext ension; t here is a lesser degree of paresis of elbow
f lexion. When t he radial nerve is involved, t he t riceps and radial ref lexes are
decreased or absent , and a variable sensory loss is present on t he ent ire
ext ensor surf ace of t he arm and f orearm and on t he back of t he hand and
dorsum of t he f irst f our f ingers.
Brachial Mononeuropathies
I njuries t o individual peripheral nerves arising direct ly f rom t he plexus are usually
relat ed t o closed t rauma (e. g. , t ract ion and compression injuries) or disease of
t he vasa nervorum (e. g. , diabet ic neuropat hy). The clinical signs involve mot or,
ref lex, and sensory dist urbances in t he ent ire dist ribut ion of each nerve involved.
These f indings are described in Chapt er 2.
Thoracic Outlet Syndrome (Cervicobrachial

Neurovascular Compression Syndrome)
The t horacic out let syndrome result s f rom compression of t he brachial plexus or
t he subclavian vessels in t he space bet w een t he f irst rib and t he clavicle
(thoraci c outl et) [22, 101, 132] .
There are usually various predisposing compressive f act ors, including a cervical
rib, an
enlarged sevent h cervical t ransverse process, a hypert rophied ant erior scalene
muscle (scal enus anti cus syndrome), clavicular abnormalit ies (congenit al or
t raumat ic), or a f ibrous band unit ing t he sevent h cervical t ransverse process t o
t he f irst rib or ant erior scalene muscle[22] .
The t horacic out let syndrome[22] may be purely vascular, purely neuropat hic, or,
rarely, mixed.
Vascular Signs and Symptoms

Vascular t horacic out let syndrome may be art erial or venous. Wit h subclavian
art ery compression t here may be recurrent coldness, cyanosis, and pallor of t he
hand. Frank gangrene of t he digit s or Raynaud's phenomenon is rare. A bruit may
be present over t he supra- or inf raclavicular areas, especially w hen t he arm is
f ully abduct ed. When t he arm is abduct ed t o 90 degrees and ext ernally rot at ed,
t he radial pulse is f requent ly oblit erat ed; how ever, pulse oblit erat ion is
occasionally seen in healt hy individuals, and t his maneuver is a poor diagnost ic
t est f or art erial compression[105] . The subclavian vein may also be compressed,
result ing in arm edema, cyanosis, and prominence of t he veins of t he arm and
chest .
Neuropathic Signs and Symptoms
True neurogenic t horacic out let syndrome is ext remely rare [22, 80, 130, 132, 133] ,
and occurs most f requent ly in young t o middle-aged w omen. Usually, t he low er
t runk or medial cord of t he brachial plexus is involved. Pain is t he most common
sensory sympt om, is of t en int ermit t ent , and is ref erred t o t he ulnar border of t he
hand and t he medial f orearm and arm [7, 81] . Parest hesias and sensory loss
may occur in t he same dist ribut ion. The mot or and ref lex f indings are essent ially
t hose of a low er plexus palsy. I nvolvement of t he low er t runk may be rest rict ed
t o t hose f ibers derived f rom t he eight h cervical root ; t heref ore, t henar w ast ing
and paresis (median innervat ion) may be prominent , w hereas ulnar-supplied
muscles are spared (t he ulnar hand muscles derive innervat ion f rom t he C8 and
T1 root s, but t he median t henar muscles are predominant ly innervat ed by t he C8
root )[ 80] . Upper plexus t horacic out let syndrome may occur rarely[86] .
A droopy shoul der syndrome has been described in pat ient s w it h t horacic out let
syndrome [114] . This syndrome consist s of t he f ollow ing signs and sympt oms:
1. Low -set , droopy shoulders, and a long sw an neck w it h horizont al or

dow nsloping clavicles
2. Pain or parest hesias in t he neck, shoulder, chest , arms, or hands
3. Aggravat ion of sympt oms by dow nw ard t ract ion and relief by propping up t he
arms
4. O ccurrence predominant ly in w omen
5. Absence of vascular, neurologic, and elect rophysiologic abnormalit ies
6. A Tinel's sign over t he brachial plexus
7. The second t horacic vert ebra visible above t he shoulder on lat eral cervical
spine f ilms
The Lumbosacral Plexus

Anatomy
The lumbosacral plexus (Fig. 3-4) derives f rom t he vent ral primary rami of t he
t w elf t h t horacic t hrough f ourt h sacral levels and is sit uat ed w it hin t he subst ance
of t he psoas major muscle. Anomalous derivat ions of t he plexus (pref ixed or
post f ixed) occur in up t o 20% of healt hy subject s. The lumbosacral plexus gives
off t he f ollow ing nerves (t he dist ribut ion areas of t hese nerves are discussed in
Chapt er 2):
1. The i l i ohypogastri c nerve (T12–L1)

2. The i l i oi ngui nal nerve (L1)
3. The geni tof emoral nerve (L1–L2)
4. The l ateral f emoral cutaneous nerve (L2–L3)
5. The f emoral nerve (L2–L4)
6. The obturator nerve (L2–L4)
7. The superi or gl uteal nerve (L4–S1)
8. The i nf eri or gl uteal nerve (L5–S2)
9. The sci ati c nerve (L4–S3)
10. The posteri or f emoral cutaneous nerve (S1–S3)
11. The pudendal nerve (S1–S4)
Lesions of the Lumbosacral Plexus

A lumbosacral plexopat hy is recognized by pain and sensorimot or def icit s in t he
dist ribut ion of mult iple spinal and peripheral nerves in t he low er ext remit y.
Common causes are neoplasms (e. g. , of t he cervix, prost at e, bladder,
colorect um, kidney, breast , t est is, or ovary, sarcomas, and lymphoma), w hich
especially aff ect t he plexus by direct invasion or by involvement of int ernal iliac,
ext ernal iliac, or low er aort ic lymph nodes[92] . I n pat ient s w it h lumbosacral
plexopat hy and pelvic t umors, t hree clinical syndromes have been delineat ed [58,
59] : (a) a low er (L4–S1) syndrome in 51%, (b) an upper (L1–L4) syndrome in
31%, and (c) a panplexopat hy (L1–S3) in 18%. Sevent y percent of t hese
pat ient s had t he insidious onset of low back, pelvic, or radicular leg pain,
f ollow ed w eeks t o mont hs lat er by sensory sympt oms
and w eakness. The quint et of leg pain, w eakness, edema, rect al mass, and
hydronephrosis should suggest plexopat hy due t o cancer[59] . I n anot her series
of 31 pat ient s w it h lumbosacral plexus met ast ases, pain w as t he most prominent
sympt om (occurred in 87% of pat ient s) w it h ot her sympt oms including w eakness
(in 74%) and parest hesias (in 68%)[ 117] . Signs in t hese pat ient s included
decreased or absent muscle st ret ch ref lexes in 81%, paresis in 81%, and
decreased sensat ion in 74%. Seven pat ient s had bilat eral signs. A hot and dry
f oot (due t o involvement of sympat het ic t runk in t he paravert ebral ret roperit oneal
region by t he t umor) may be t he init ial manif est at ion of a neoplast ic lumbosacral
plexopat hy[ 23] . Radiat ion t herapy may also cause a lumbosacral plexopat hy, and
it is of t en diff icult t o clinically dist inguish a plexopat hy due t o radiat ion f rom t hat
due t o recurrent neoplasm or met ast ases [118, 119] . The clinical present at ion
may help dist inguish t hese t w o causes of lumbosacral plexopat hy[118] . Wit h
t umor recurrence, pain is marked at onset and usually proxi mal (i. e. , locat ed in
t he t high, but t ock, and hip), and unilat eral leg paresis is t ypical. Wit h radiat ion-
induced plexopat hy, unilat eral or bilat eral indolent (usually di stal ) leg w eakness
is present early, and pain is evident in only 50% of individuals. Clinical or
elect rical myokymia w as evident in 12 of 20 pat ient s w it h radiat ion plexopat hy.
Parest hesias are uncommon in bot h t umor and radiat ion-induced cases.
Radiat ion may also induce malignant and at ypical peripheral nerve sheat h t umors
of t he lumbar plexus[39] .
FI G URE 3-4 The lumbosacral plexus
Acut e painless ischemic lumbosacral plexopat hy, of t en w it hout signs of limb

ischemia, may occur w it h aort ic dissect ion [42, 79] . I schemia of t he plexus is
t hought t o be due t o int errupt ion of blood f low t hrough t he lumbar segment al
art eries and branches of t he iliac art eries secondary t o dissect ion of t he aort ic
w alls and t he most proximal iliac art ery w alls just below t he aort ic bif urcat ion.
Such ischemic lumbosacral plexopat hies have also been described af t er
aort of emoral or aort oiliac graf t surgery by resect ion of nut rient art eries, af t er
use of an int ra-aort ic balloon, af t er vasospasm caused by inject ion of drugs int o
t he inf erior glut eal or umbilical art ery, and af t er int ra-art erial (usually iliac
art ery) inf usion of chemot herapeut ic agent s f or pelvic malignancies
[ 42, 46, 79, 112, 118] .
Foot drop may be a harbinger of an ischemic lumbosacral plexopat hy preceding

ident if icat ion of aort ic occlusion[75] , and exercise-induced ischemia of t he
lumbosacral plexus may occur in pat ient s w it h high-grade st enosis or occlusion
of t he art erial supply of t he plexus[137] .
O t her et iologies f or lumbosacral plexopat hy include ret roperit oneal hemorrhage
(e. g. , f rom ant icoagulant t herapy or as a complicat ion of hemophilia), psoas
abscess (e. g. , f rom t uberculosis or pyogenic ost eomyelit is), t rauma (e. g. , pelvic
f ract ures or gunshot w ounds), surgery (especially pelvic procedures and
abdominal aort ic surgery), diabet es, herpesvirus inf ect ions, int ravenous
administ rat ion of heroin, and idiopat hic ret roperit oneal f ibrosis[119] . I n pat ient s
w it h pelvic t rauma, lumbosacral plexopat hy is most of t en not ed w it h sacral
f ract ures, sacroiliac joint separat ion, acet abular f ract ures, or f emoral
f ract ures[ 72] . I n pat ient s w it h t raumat ic lumbosacral plexopat hies, t he low er
port ion of t he plexus is more of t en involved in case of mot or vehicle accident s,
w hereas t he upper port ion of t he plexus is more of t en involved in case of
gunshot w ounds[21] . The diagnosis of retroperi toneal hematoma must be
suspect ed in any pat ient receiving ant icoagulant s w ho complains of back, groin,
t high, or leg pain. Physical examinat ion in t hese pat ient s may reveal
suprainguinal t enderness, and t he pain may be aggravat ed by leg ext ension.
O t her clinical f indings include a charact erist ic f lexion and ext ernal rot at ion of t he
aff ect ed ext remit y. Somet imes t he hemat oma present s as a groin mass.
Neuropat hies involving t he f emoral nerve, t he obt urat or nerve, and t he lat eral
f emoral cut aneous nerve are common. There may also be mild cardiovascular
inst abilit y and evidence of blood loss and a decrease in hemat ocrit level. Most
cases of ret roperit oneal hemat omas are due t o t he administ rat ion of int ravenous
or subcut aneous heparin. Because of t he narrow t herapeut ic index and pot ent ial
int eract ions of w arf arin w it h ot her drugs, pat ient s receiving t his medicat ion
should be caref ully monit ored f or pot ent ial complicat ions. Ret roperit oneal
hemat omas may be t raumat ic or nont raumat ic. O t her rare causes of
ret roperit oneal hemat oma include rupt ured aort ic aneurysms, t raumat ic aort ic
rupt ure, rupt ured ovarian art ery aneurysms, rupt ured lumbar art ery
pseudoaneurysms, rupt ured pseudoaneurysms f ollow ing acupunct ure, f emoral
vein cannulat ion, cardiac cat het erizat ion, ext racorporeal shock w ave lit hot ripsy,
rupt ured aneurysms in polyart erit is nodosa, pudendal blocks, acquired f act or
VI I I –specif ic ant ibodies, pelvic f ract ure, and t ot al hip art hroplast y.
Ret roperit oneal hemat omas f ollow ing cardiac cat het erizat ion are t hought t o arise
f rom inadvert ent punct ure of t he dist al ext ernal iliac art ery and are more
prevalent in associat ion w it h placement s of coronary art ery st ent s; most pat ient s
are t reat ed w it h t ransf usion alone, and a small subset of pat ient s unresponsive
t o volume expansion require surgery [1, 2, 3, 20, 47, 49, 54, 62, 63, 67, 88, 111, 134] .
During labor and delivery, t he descending f et al head may compress t he
lumbosacral t runk as it passes over t he pelvic rim [36, 65] . I nt rapart um mat ernal
lumbosacral plexopat hy usually occurs in w omen of short st at ure and present s
w it h w eakness of ankle dorsif lexion, eversion, and inversion, associat ed w it h
sensory loss in an L5 dermat ome[65] . The result ant f oot drop is almost alw ays
unilat eral and, generally, on t he same side as t he inf ant 's brow during t he
descent . Post part um lumbosacral plexopat hy may occur af t er vaginal delivery
and may be limit ed t o aut onomic and perineal manif est at ions (e. g. , urinary
diff icult y, anorect al impairment , and sexual dysf unct ion) involving only S2–S4
w it hout limb sensory or mot or signs[57] .
Di abeti c l umbosacral radi cul opl exus neuropathy (DLRPN) (also called di abeti c
amyotrophy) is a w ell-recognized subacut e, painf ul, asymmet ric low er limb
neuropat hy t hat is associat ed w it h w eight loss and t ype 2 diabet es mellit us.
Nondi abeti c l umbosacral radi cul opl exus neuropathy (LRPN) has received less
at t ent ion [13, 30, 31, 32, 121, 126] . Comparison of large cohort s w it h DLRPN and
LRPN has demonst rat ed t hat age at onset , course, t ype and dist ribut ion of
sympt oms and impairment s, laborat ory f indings, and out comes are similar. Bot h
condit ions are lumbosacral radiculoplexus neuropat hies t hat are associat ed w it h
w eight loss and begin subacut ely and f ocally w it h pain but evolve int o
w idespread, bilat eral paralyt ic disorders. The disorder of t en begins f ocally or
asymmet rically in t he t high or leg but usually progresses t o involve t he init ially
unaff ect ed segment and t he cont ralat eral side. Alt hough bot h are monophasic
illnesses, pat ient s have prolonged morbidit y f rom pain and w eakness, and many
pat ient s become w heelchair-dependent . Alt hough mot or predominant , t here is
unequivocal evidence t hat aut onomic and sensory nerves are also involved.
Cut aneous nerves f rom pat ient s w it h DLRPN and LRPN show pat hologic evidence
of ischemic injury and microvasculit is. I t is likely t hat DLRPN and LRPN are
immune-mediat ed neuropat hies t hat should be separat ed f rom chronic
inf lammat ory demyelinat ing polyneuropat hy and syst emic necrot izing vasculit is
[ 30, 31, 32] . Recurrent
idiopat hic lumbosacral plexopat hy has also been described[141] .

Most injuries t o t he lumbosacral plexus primarily involve t he lumbar segment s,
sacral segment s, or individual peripheral nerves. The individual peripheral nerve
syndromes are described in Chapt er 2.
Lesions of the Entire Lumbosacral Plexus

Lesions of t he ent ire plexus are rare and are usually incomplet e. They result in
paralysis or paresis of t he ent ire low er ext remit y, w it h hyporef lexia or aref lexia
and sensory dist urbance aff ect ing t he ent ire leg.
Lesions of the Lumbar Segments

Lesions of t he lumbar segment s are also usually incomplet e, and t hey are most
of t en due t o t umor, hemorrhage, or surgical injury. I f t he ent ire lumbar plexus is
injured, a syndrome t hat exhibit s t he f ollow ing signs w ill result .
Motor Si gns. There is paresis and at rophy, predominant ly in t he mot or

dist ribut ions of t he f emoral and obt urat or nerves. Theref ore, t here is
w eakness of t high f lexion (iliopsoas), leg ext ension (quadriceps), t high
eversion (sart orius), and t high adduct ion (adduct or muscles).
Sensory Si gns. Sensat ion may be lost in t he inguinal region and over t he
genit alia (innervat ed by iliohypogast ric, ilioinguinal, and genit of emoral
nerves); on t he lat eral, ant erior, and medial t high (innervat ed by t he lat eral
f emoral cut aneous, f emoral, and obt urat or nerves, respect ively); and on t he
medial aspect of t he low er leg (innervat ed by t he saphenous nerve, a branch
of t he f emoral nerve).
Ref l ex Si gns. The pat ellar ref lex (f emoral nerve) and cremast eric ref lex
(genit of emoral nerve) may be decreased or absent .
Lesions of the Sacral Plexus

Lesions of t he sacral plexus are f requent ly incomplet e and occur most commonly
w it h neoplasms or surgical t rauma. I f t he ent ire sacral plexus is injured, t he
f ollow ing syndromes result .
Motor Si gns. Lesions of t he sacral plexus result in mot or dist urbances in t he

f ield of dist ribut ion of t he superior glut eal, inf erior glut eal, and sciat ic
nerves. A “f lail f oot ” result s because of paralysis of t he dorsif lexors and
plant ar f lexors of t he f oot . There is w eakness of knee f lexion (hamst rings),
f oot eversion (peronei), f oot inversion (t ibialis ant erior and post erior), f oot
plant ar f lexion (gast rocnemius and soleus), t oe dorsif lexion (ext ensors of
t oes), and t oe plant ar f lexion (plant ar f lexors of t oes); all t hese muscles are
in t he sciat ic dist ribut ion area. Paresis of abduct ion and int ernal rot at ion of
t he t high (superior glut eal nerve palsy) and hip ext ension (inf erior glut eal
nerve palsy) occur.
Sensory Si gns. Sensat ion may be lost in t he dist ribut ion area of t he sciat ic
nerve (out er leg and dorsum of t he f oot , sole, and inner aspect of t he f oot )
and in t he dist ribut ion of t he post erior f emoral cut aneous nerve (post erior
t high and poplit eal f ossa).
Ref l ex Si gns. The Achilles ref lex (ankle jerk) may be decreased or absent
because of sciat ic nerve involvement .
Sphi ncter Si gns. Diff icult y in bladder or bow el cont rol may result f rom injury
t o t he pudendal nerve.
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> Table of C ontents > C hapter 4 - S pinal Ner ve and R oot
Chapter 4
Spinal Nerve and Root
Anatomy of the Spinal Nerves and Roots

The aff erent (sensory) f ibers (Fig. 4-1) f rom t he peripheral nervous syst em ent er
t he spinal cord in t he dorsal roots and have t heir perikarya in t he dorsal spi nal
root gangl i a. The dorsal root s ent er t he cord in t he dorsolat eral sulcus. The
eff erent (mot or) f ibers arise f rom t he mot or neurons locat ed in t he vent ral horns
of t he spinal cord and exit t he cord as t he ventral roots. The vent ral and dorsal
root s unit e t o f orm t he mi xed spi nal nerve, w hich t hen t ravels t hrough t he
int ervert ebral f oramen. Af t er emerging f rom t he f oramen, t he spinal nerve divides
int o ant erior and post erior primary rami. The smaller posteri or pri mary rami
supply t he skin on t he dorsal aspect of t he t runk w it h sensory f ibers and also
send mot or f ibers t o t he longit udinal muscles of t he axial skelet on. The anteri or
pri mary rami supply t he limbs (see Chapt er 3), nonaxial skelet al muscles, and
skin of t he lat eral and ant erior t runk and neck (by w ay of t he l ateral cutaneous
and anteri or cutaneous branches, respect ively). The ant erior primary rami also
communicat e w it h t he sympat het ic ganglia t hrough whi te and gray rami
communi cantes.
Principles of Spinal Nerve and Root Localization

The ident if icat ion of spinal nerve lesions requires a precise know ledge of each
group of muscles supplied by a single ant erior spinal root (myotome) and each
cut aneous area supplied by a single post erior spinal root (dermatome) (Fig. 4-
2). Diff erent iat ion f rom peripheral nerve or plexus lesions t hereby depends on
t he segmental charact er of t he sensory and mot or signs and sympt oms.
Sensory Symptoms
I rrit at ive lesions of a dorsal root result in radi cul ar pai n or root pai n, w hich has
a charact erist ic lancinat ing, elect ric, or burning qualit y. This pain is abrupt ,
sharp, w ell localized, ref erred t o a specif ic dermat ome or myot ome, and
charact erist ically accent uat ed or precipit at ed by maneuvers t hat cause increased
int raspinal pressure or st ret ching of t he dorsal nerve root (e. g. , coughing,
st raining, sneezing, Valsalva's maneuver, or spine movement s). Pain is of t en t he
f irst manif est at ion of a sensory radiculopat hy and may be associat ed w it h
parest hesias or dysest hesias in t he area involved.
Dest ruct ive dorsal root lesions result in hypest hesia or anest hesia t hat is
conf ined t o t he specif ic dermat ome involved. Because of t he overlap of
cut aneous supply by adjacent nerve root s, sect ioning of a single dorsal root
result s in lit t le or no sensory loss. Theref ore, t he absence of sensory loss does
not exclude t he possibilit y of a lesion aff ect ing a single dorsal root . When
mult iple dorsal root lesions are present , sensory loss is evident , t he area of
analgesia being larger t han t he area of anest hesia t o light t ouch.
Motor Signs
Vent ral root lesions result in w eakness and at rophy in t he myot omal dist ribut ion
of t he aff ect ed root . Fasciculat ions may be evident in t he aff ect ed muscle.
Reflex Signs
Lesions of t he dorsal or vent ral root may int errupt t he aff erent or eff erent arc,
respect ively, of a specif ic muscle st ret ch ref lex. Theref ore, w it h
vent ral or dorsal lesions, hypo- or aref lexia occurs in t he muscle subserved by
t he aff ect ed spinal root .
FI G URE 4-1 Anat omy of t he spinal nerves and root s

Etiologies of Spinal Nerve and Root Lesions
The spinal root s may be injured by direct (e. g. , missile or penet rat ing w ounds)
or indirect (e. g. , spinal t ract ion) t rauma and are f requent ly compressed by
lesions in and about t he int ervert ebral f oramina (e. g. , disc disease, spondylosis,
a hypert rophied ligament um f lavum, or primary or met ast at ic t umors of t he
vert ebrae or spinal nerves). The most common disc prolapse in t he cervical
region is at t he C6–C7 int erspace, result ing in signs and sympt oms of C7 root
involvement [14, 15, 24] . I n t he lumbar region, t he most common disc prolapse is
at t he L4–L5 or L5–S1 level, result ing in signs and sympt oms ref erable t o t he L5
or S1 root s, respect ively. The neurologic signs and sympt oms not ed w it h
irrit at ion or damage of individual nerve root s by disc prolapse are out lined in
Table 4-1.
A lumbosacral radiculopat hy, most of t en involving t he L2 level, and a
polyradiculoneuropat hy may occur as a complicat ion of epidural analgesia or
anest hesia[ 37] . A post radiat ion lumbosacral radiculopat hy may occur years af t er
irradiat ion of paraaort ic lymph nodes in pat ient s w it h neoplasms, especially
t est icular cancer[4] . These pat ient s develop a mot or disorder predominant ly
aff ect ing t he legs w it h mild sensory and sphinct er abnormalit ies.
Cert ain generalized peripheral nervous syst em diseases have a predilect ion f or
t he spinal root s (e. g. , G uillain-Barré syndrome). Herpes zost er t ypically occurs
in t he dist ribut ion of sensory dermat omes, most of t en at a t horacic level[5, 32] .
Unilat eral or bilat eral radiculopat hies may occur w it h Lyme disease, especially
aff ect ing t he f if t h cervical dermat ome or low er t horacic levels [7, 8, 20] .
Diabet es may cause t horacic root pain[10] or t horacoabdominal neuropat hy[30,
31] , present ing w it h severe abdominal or chest pain, of t en not radicular in
charact er. The presence of dysest hesias and abnormal f indings on sensory
examinat ion of t he t runk aid in t he diagnosis of t hese
diabet ic neuropat hies. Diabet ic t runcal neuropat hy may result in sensory changes
in a complet e dermat omal band, in mult iple dermat omal levels, in t he dist ribut ion
of t he vent ral or dorsal rami of t he spinal nerves or branches of t hese rami, or in
varying combinat ions of t hese dist ribut ions[30] . Diabet ic t runcal neuropat hy may
rarely present w it h f ocal, unilat eral prot rusion of t he abdominal w all
(pseudohernia), w hich may be associat ed w it h spont aneous, burning abdominal
pain and hyperpat hia or w hich may be painless[21, 34] .
FI G URE 4-2 Map of dermat omes
TABLE 4-1 Neurologic Signs and Symptoms w ith Nerve

Irritation or Damage from Disc Disease
Sensory Motor Re
Root Disc Pain
Findings Findings Ch
Neck, Deltoid,
external Bic
C4– shoulder,
C5 Lateral arm rotators of bra
C5 and anterior
arm, rad
arm
forearm
flexors
Forearm
Lateral
flexion,
forearm,
Lateral arm arm Bic
C5– lateral arm,
C6 and dorsal pronation, bra
C6 and first
forearm finger and rad
and second
wrist
digits
extension
Arm
extension,
C6– Dorsal Third and finger and
C7 Tri
C7 forearm fourth digits wrist
flexors and
extensors
Medial Medial
Intrinsic
C7– forearm and forearm and Fin
C8 hand
T1 hand, fifth hand, fifth fle
muscles
digit digit
Low back,
buttock,
L3– Knee and Knee
L4 anterolateral Pa
L4 medial leg extension
thigh,
anterior leg
Low back, Thigh
Lateral leg, adduction,
buttock,
L4– dorsomedial knee
L5 lateral thigh, No
L5 foot, large flexion and
anterolateral
toe dorsiflexion
calf
of foot and
toes
Hip
Low back, extension,
Lateral foot,
L5– buttock, plantar
S1 sole of foot, Ac
S1 lateral thigh, flexion of
small toe
calf foot and
toes
Pat ient s w it h acquired immunodef iciency syndrome may develop a dist inct ive
syndrome of rapidly progressive f laccid paraparesis and aref lexia t hat is
f requent ly associat ed w it h sphinct er dist urbances[29] . This acut e lumbosacral
polyradiculopat hy may have mult iple causes, including cyt omegalovirus inf ect ion,
met ast asis f rom syst emic lymphoma, or unknow n causes [2, 6, 18, 27, 29] .
The Localization of Nerve Root Syndromes

Lesions Affecting the Cervical Roots
Lesions aff ect ing t he spinal nerves and root s[35, 36] give rise t o mot or and
sensory segment al def ect s and charact erist ic dist urbances in muscle st ret ch
ref lexes. Each cervical segment is considered in more det ail in t his sect ion. The
individual spinal nerve root syndromes discussed are t heoret ical because clinical
pract ice of t en present s lesions t hat aff ect mult iple segment s.
Lesions Affecting C1
Because t here is no dorsal root f rom C1, lesions of t his root result in purely
mot or sympt oms. This root supplies muscles t hat support t he head, f ix t he neck,
assist in neck f lexion and ext ension,
and t ilt t he head t o one side. These, include t he longus capit is, rect us capit is,
obliquus capit is, longissimus capit is and cervicis, mult if idi, int ert ransversarii,
rot at ores, semispinalis, and inf rahyoid muscles. C1 lesions usually result in
minor mot or diff icult ies.
Sensory sympt oms and signs due t o C2 lesions are localized t o t he scalp
post erior t o t he int eraural line (t he C2 dermat ome). The mot or supply of t his
segment involves t he same muscles responsible f or head and neck movement s
as t hose innervat ed by segment C1. I n addit ion, t he C2 nerve helps supply t he
st ernocleidomast oid muscle (head rot at ion and f lexion), w hich is predominant ly
innervat ed by t he spinal accessory nerve (cranial nerve XI ).
Sensory dist urbances occur on t he low er occiput , t he angle of t he jaw, and t he
upper neck[23] . Paresis may occur in t he scalene and levat or scapulae muscles
of t he neck (including t he inf rahyoids, semispinalis capit is and cervicis,
longissimus capit is and cervicis, int ert ransversarii, rot at ores, mult if idi), and in
t he t rapezius (shoulder elevat ion), t his last muscle being predominant ly
innervat ed by t he spinal accessory nerve (cranial nerve XI ). Diaphragmat ic
paresis may also result because t he phrenic nerve receives some of it s f ibers
f rom t he C3 segment .
I rrit at ion of t he C3 nerve root may cause a painf ul, burning, red ear (red ear
syndrome)[ 12] . The increased ear t emperat ure may be caused by ant idromic
release of vasodilat or pept ides. This red ear syndrome may also occur w it h
t emporomandibular joint dysf unct ion and w it h t halamic lesions[12] .
Sensory signs and sympt oms occur on t he low er neck. Paresis occurs in t he
scalene and levat or scapulae muscles (lat eral neck f lexion and scapular rot at ion,
respect ively), rhomboid muscles (scapular elevat ion and adduct ion), t rapezius
muscle (shoulder elevat ion), and some muscles of t he neck. Diaphragmat ic
paresis may also occur because some f ibers t o reach t he phrenic nerve. There is
no ref lex impairment .
C5 nerve root involvement result s in neck, shoulder, and upper ant erior arm pain.
Sensory dist urbances occur on t he lat eral arm w it h t hese lesions. Paresis occurs
predominant ly and variably in t he f ollow ing muscles: levat or scapulae,
rhomboids, serrat us ant erior, supraspinat us, inf raspinat us, delt oid, biceps, and
brachioradialis (f or met hods of examinat ion of each of t hese muscles, see
Chapt er 2). Diaphragmat ic paresis may rarely occur ow ing t o C5 f ibers reaching
t he phrenic nerve. The biceps ref lex (subserved by segment s C5–C6) and t he
brachioradialis ref lex (C5–C6) may be depressed.
This nerve root is of t en compressed by disc herniat ion at t he C5–C6 vert ebral
level. A monoradiculopat hy aff ect ing t he C6 nerve root is t he second most
common level of cervical radiculopat hy af t er lesions of t he C7 level[24] . C6 root
involvement result s in pain in t he lat eral arm and dorsal f orearm. Sensory signs
and sympt oms occur on t he lat eral f orearm, lat eral hand, and t he f irst and
second digit s. Paresis occurs predominant ly in t he f ollow ing muscles: serrat us
ant erior, biceps, pronat or t eres, f lexor carpi radialis, brachioradialis, ext ensor
carpi radialis longus, supinat or, and ext ensor carpi radialis brevis (examinat ion
of t hese muscles is described in Chapt er 2). The biceps ref lex (segment s C5–
C6) and t he brachioradialis ref lex (segment s C5–C6) may be depressed. An
“invert ed radial ref lex” occurs w hen t he lesion causes compression of t he spinal
cord at t he C5–C6 level. A cent ral disc prolapse or a horizont al bar due t o
degenerat ive disc disease is of t en responsible f or t his clinical f inding. Damage
of t he cort icospinal t ract at t he level of C5–C6 result s in hyperref lexia at low er
levels. Theref ore, t apping t he t endon of t he brachioradialis muscle elicit s no
response by t he brachioradialis but a brisk cont ract ion of t he f inger f lexors
innervat ed by t he C8–T1 segment s.
This nerve root is of t en compressed by disc herniat ion at t he C6–C7 vert ebral
level (t he most common level of disc herniat ion)[ 15, 24] . C7 root involvement
result s in pain in t he dorsal f orearm. I n some pat ient s, pain may be subscapular
or locat ed in t he deep breast or chest [19] . Sensory dist urbances occur on t he
t hird and f ourt h digit s. Paresis occurs variably in t he f ollow ing muscles: serrat us
ant erior, pect oralis major, lat issimus dorsi, pronat or t eres, f lexor carpi radialis,
t riceps, ext ensor carpi radialis longus, ext ensor carpi radialis brevis, and
ext ensor digit orum (examinat ion of t hese muscles is described in Chapt er 2). The
t riceps ref lex (C7–C8) may be depressed.
Pseudomyotoni a is a t erm applied t o t he diff icult y in opening t he hand because
of cervical ost eoart hrit is. Muscle relaxat ion is normal but at t empt s t o ext end t he
f ingers produce paradoxical
f lexion of t he f ingers, probably as a result of misdirect ed regenerat ion of C7

nerve root f ibers[28] .
This nerve root is of t en compressed by disc herniat ion at t he C7–T1 vert ebral
level. C8 root involvement result s in pain in t he medial arm and f orearm. Wit h C8
lesions[ 33] , sensory signs and sympt oms occur on t he medial f orearm and hand
and on t he f if t h digit . Paresis occurs predominant ly and variably in t he f ollow ing
muscles: f lexor digit orum superf icialis, f lexor pollicis longus, f lexor digit orum
prof undus I t o I V, pronat or quadrat us, abduct or pollicis brevis, opponens pollicis,
f lexor pollicis brevis, all lumbricals, f lexor carpi ulnaris, abduct or digit i minimi,
opponens digit i minimi, f lexor digit i minimi, all int erossei, adduct or pollicis,
ext ensor digit i minimi, ext ensor carpi ulnaris, abduct or pollicis longus, ext ensor
pollicis longus and brevis, and ext ensor indicis (see Chapt er 2 f or examinat ion
met hods of t hese muscles). The f inger f lexor ref lex (C8–T1) may be depressed.
Sympat het ic f ibers dest ined f or t he superior cervical ganglia are int errupt ed,
result ing in an ipsilat eral Horner syndrome (pt osis, miosis, and anhidrosis).
There are f requent int radural communicat ing f ibers bet w een neighboring
segment s of t he cervical post erior root s. These connect ions are most prominent
bet w een a specif ic cervical segment and t he next caudal root . A lesion may
t heref ore be f alsely localized clinically t o a segment one level higher t han it s
act ual locat ion.
The t heoret ical root syndromes discussed earlier are also relat ed t o an
“idealized” brachial plexus and do not t ake int o considerat ion t he possibilit y of a
pref ixed or post f ixed plexus (see Chapt er 3).
Lesions Affecting the Thoracic Roots

Lesions Affecting T1
Sensory dist urbances occur on t he medial arm. Paresis occurs variably in t he
f ollow ing muscles: abduct or pollicis brevis, opponens pollicis, f lexor pollicis
brevis, all lumbricals and int erossei, abduct or digit i minimi, opponens digit i
minimi, f lexor digit i minimi, and adduct or pollicis[13] . The f inger f lexor ref lex
(C8–T1) may be depressed. Sympat het ic f ibers dest ined f or t he superior cervical
ganglia are int errupt ed, result ing in an ipsilat eral Horner syndrome.
Lesions Affecting Segments T2–T12

Lesions aff ect ing t he t horacic root s and spinal nerves are diff icult t o diagnose
because t horacic and abdominal muscles are diff icult t o evaluat e and t here are
no muscle st ret ch ref lexes subserved by t hese levels. Theref ore, clinical
diagnosis relies predominant ly on sensory sympt oms and signs.
Thoracic nerves supply (by w ay of t he int ercost al nerves) t he int ercost al and
abdominal muscles, w hich f unct ion predominant ly in elevat ion and depression of
t he ribs, cont ract ion of t he abdomen, and f lexion of t he t runk. Thoracic nerve
lesions result in int ercost al muscle paralysis, w hich causes ret ract ion of t he
cost al int erspace during inspirat ion and bulging of t he int erspace during cough or
a Valsalva's maneuver. Low er t horacic and upper lumbar root lesions may result
in excessive prot rusion of t he abdomen during inspirat ion. When t he abdominal
muscles are aff ect ed t here may be diff icult y in rising f rom a recumbent posit ion,
and if t hese muscles are paralyzed unilat erally t he umbilicus is pulled t ow ard t he
normal side during inspirat ion or head elevat ion against resist ance (w hile t he
pat ient is in t he prone posit ion). When t here is bilat eral low er abdominal muscle
paresis below or at t he T10 level, t his maneuver result s in elevat ion of t he
umbilicus (Beevor's si gn). Sensory dist urbances are of t en predominant ly or
solely subject ive. The pat ient complains of severe burning parest hesias or
light ninglike pains. These occur in a unilat eral or bilat eral segment al dist ribut ion
(radiat ing around t he t horax or abdomen) and are precipit at ed by any maneuver
t hat causes increased int raspinal pressure or st ret ching of t he dorsal root
(coughing, sneezing, Valsalva's maneuver, neck f lexion, spine movement s). There
may be sensory loss in t he t horacic dermat ome involved, but because of t he
overlapping cut aneous supply by adjacent nerve root s, complet e sect ion of a
single dorsal root result s in lit t le or no sensory loss.
A benign condit ion of unknow n et iology, t ermed notal gi a parestheti ca, has been
described in w hich burning, prurit us, and parest hesias develop over an area
(approximat ely t he size of t he palm of t he hand) at t he medial margin of t he
scapula[ 22] . Decreased sensit ivit y t o pain may occur in t his area, w hich is likely
in t he t errit ory of t he dorsal branches of root s T2 t o T6.
Lesions of the Lumbar and Sacral Roots

Lesions Affecting L1
Sensory signs and sympt oms occur mainly in t he inguinal region. Low er
abdominal paresis (int ernal oblique, t ransversus abdominis) may occur but is
diff icult t o demonst rat e.
Sensory dist urbances occur on t he ant erior t high. Paresis may be present in t he
pect ineus (t high adduct ion, f lexion, and eversion), iliopsoas (t high f lexion),
sart orius (t high f lexion and eversion), quadriceps (leg ext ension), and t high
adduct ors. The cremast eric ref lex (L2) may be depressed. Wit h upper lumbar
root lesions (L2–L4), t he result of bent-knee pul l i ng test is of t en posit ive[9] . The
examiner pulls t he half -prone pat ient 's knee backw ard w hile put t ing f orw ard
pressure on t he but t ock; t he t est result is posit ive w hen lumbar radicular pain is
elicit ed.
Sensory signs and sympt oms occur on t he low er ant erior t high and medial aspect
of t he knee. Paresis occurs variably in t he pect ineus (t high adduct ion, f lexion,
and eversion), iliopsoas (t high f lexion), sart orius (t high f lexion and eversion),
quadriceps (leg ext ension), and t high adduct ors. The pat ellar ref lex (L2–L4) may
be depressed.
L4 root involvement causes low er back, but t ock, ant erolat eral t high, and ant erior
leg pain. Sensory dist urbances occur on t he knee and t he medial leg. Paresis
occurs variably in t he quadriceps (leg ext ension), sart orius (t high f lexion and
eversion), and t ibialis ant erior (f oot dorsif lexion and inversion). The pat ellar
ref lex (L2–L4) may be depressed. Rarely, neurogenic hypertrophy of t he t ibialis
ant erior muscle may occur w it h a chronic L4 lesion, perhaps because of
excessive spont aneous muscle act ivit y[16] .
A recent st udy evaluat ed f our off ice t est s of quadriceps st rengt h in sympt omat ic
adult s w it h radiographic evidence of L3 or L4 nerve root compression[25] . The
st udy observed t he perf ormance of each t est f or it s abilit y t o det ect quadriceps
w eakness w hen compared t o t he asympt omat ic side. To det ermine t he pot ent ial
inf luence of radicular pain on t he perf ormance of t he f our t est s, a cont rol group
of pat ient s older t han 40 years w it h clinical and radiographic L5 or S1
radiculopat hies underw ent ident ical t est ing of quadriceps st rengt h. The L3 and
L4 nerve root s innervat e t he quadriceps; t heref ore, quadriceps w eakness may
be a consequence of L3 or L4 radiculopat hies. Thirt y-t hree consecut ive pat ient s
w it h L3 or L4 radiculopat hies and 19 w it h L5 or S1 radiculopat hies w ere st udied.
The f our t est s of quadriceps st rengt h included: (a) single leg sit -t o-st and t est
(w it h t he seat ed pat ient asked t o ext end one leg, hold t hat f oot above t he f loor,
and rise t o a st anding posit ion w it h t he ot her leg; t he pat ient could hold t he
examiner's hand f or balance); (b) st ep-up t est (w it h t he pat ient st epping up ont o
a st andard 7-inch st ep-st ool, again holding t he examiner's hand f or balance); (c)
knee-f lexed manual muscle t est ing (w it h t he pat ient supine, t he hip f lexed t o 90
degrees, t he knee maximally f lexed, t he pat ient at t empt s t o ext end t he knee
against t he examiner's resist ance); and (d) knee-ext ended manual muscle t est ing
(as in t he knee-ext ended manual t est but w it h t he knee ext ended and t he
examiner t rying t o overcome knee ext ension). I n L3 and L4 radiculopat hies,
unilat eral quadriceps w eakness w as det ect ed by t he single leg sit -t o-st and t est
in 61%, by knee-f lexed manual muscle t est ing in 42%, by st ep-up t est in 27%
and by knee-ext ended manual muscle t est ing in 9% of pat ient s. The sit -t o-st and
t est det ect ed w eakness in all but one case in w hich w eakness w as det ect ed by
anot her t est . All pat ient s w it h L5 or S1 radiculopat hies could perf orm t he sit -t o-
st and t est . I t w as concluded t hat in L3 and L4 radiculopat hies, unilat eral
quadriceps w eakness w as best det ect ed by a single leg sit -t o-st and t est .
Pat ient s of similar age w it h radicular pain caused by L5 or S1 radiculopat hies
could perf orm t his t est . As t he int errat er reliabilit y of t he single leg sit -t o-st and
t est is high, clinicians should consider ut ilizing t his t est f or assessing t he
quadriceps st rengt h in cases of L3 and L4 radiculopat hies[25] .
L5 root involvement causes low er back, but t ock, lat eral t high, and ant erolat eral
calf pain. Sensory signs and sympt oms occur on t he lat eral leg, t he dorsomedial
f oot , and t he large t oe. Paresis occurs in t he glut eus medius, glut eus minimus,
t ensor f asciae lat ae (adduct ion and int ernal rot at ion of t high), semimembranosus
and semit endinosus (knee f lexion), t ibialis post erior (plant ar f lexion and inversion
of f oot ), t ibialis ant erior (dorsif lexion and inversion of f oot ), peronei (f oot plant ar
f lexion and eversion), f lexor digit orum longus (plant ar f lexion of f oot and all t oes
except t he large t oe), ext ensor digit orum brevis (ext ension of t he large t oe and
t hree medial t oes), ext ensor hallucis longus (ext ension of great t oe and f oot
dorsif lexion), and ext ensor digit orum longus (ext ension of f our lat eral t oes and
f oot dorsif lexion). Wit h L5 root lesions, bot h t he pat ellar (L2–L4) and Achilles
(S1–S2) ref lexes are spared.
Lesions Affecting S1
S1 root involvement causes low er back, but t ock, lat eral t high, and calf pain.
Sensory dist urbances
occur on t he lit t le t oe, lat eral f oot , and most of t he sole of t he f oot . Paresis
occurs in t he glut eus maximus (hip ext ension), biceps f emoris (knee f lexion),
gast rocnemius and soleus (plant ar f lexion of f oot ), f lexor hallucis longus (plant ar
f lexion of f oot and t erminal phalanx of great t oe), f lexor digit orum longus (plant ar
f lexion of f oot and all t oes except t he large t oe), all of t he small muscles of t he
f oot , and ext ensor digit orum brevis (ext ension of large t oe and t hree medial
t oes). Rarely, an S1 radiculopat hy may result in unilat eral calf enlargement [17] ,
likely because of a combinat ion of increased amount s of connect ive t issue and
f at and a varying degree of muscle f iber hypert rophy and at rophy[26] . The
Achilles ref lex (S1–S2) is depressed.
Lesions Affecting S2–S5

Sensory dist urbances occur on t he calf , post erior t high, but t ock, and perianal
region. Bladder and bow el cont rol may be impaired. The ext ernal anal sphinct er
may f ail t o cont ract in response t o pricking of t he skin or mucous membrane of
t he perianal region (absent anal wi nk).
The Localization of Lumbosacral Disc Disease

Herniat ion of a lumbar int ervert ebral disc may result in root compression (Table
4-1). Almost all lumbar herniat ions occur bet w een t he f ourt h and f if t h lumbar or
t he f if t h lumbar and f irst sacral int erspaces. Not only t he int erspace level but
also t he locat ion of t he prot ruded disc det ermines w hich root s are predominant ly
aff ect ed (Fig. 4-3). For example, an L4–L5 prot rusion t hat occurs
post erolat erally aff ect s t he L5 root dest ined t o leave t he canal in t he L5–S1
f oramen. A very l ateral L4–L5 prot rusion, how ever, may aff ect t he L4 root
t raversing t he L4–L5 int erspace, and a very medi al lesion may aff ect t he S1 root
in it s dow nw ard course. Cent ral disc herniat ions are less common and may
act ually aff ect root s on bot h sides, result ing in bilat eral pain, aut onomic
paralysis of t he bladder and bow el, saddle anest hesia, and bilat eral low er
ext remit y w eakness (cauda equina syndrome) (see Chapt er 5).
Similarly, a very l ateral disc prot rusion at L5–S1 aff ect s t he L5 root (w hich
leaves t he canal in t he L5–S1 int erspace), w hereas t he usual posterol ateral
prot rusion causes sympt oms ref erable predominant ly t o an S1 dist ribut ion.
A t horough know ledge of t his int ervert ebral space–nerve root relat ionship is
necessary t o localize t hese nerve root syndromes accurat ely t o t he appropriat e
sit es of disc herniat ion.
FI G URE 4-3 Lumbosacral disc prot rusions. A: Medial disc prot rusion. B:
Post erolat eral disc prot rusion. C: Very lat eral disc prot rusion
The clinical syndrome of neurogeni c pseudocl audi cati on of the cauda equi na[ 3]
most commonly result s f rom lumbar st enosis. The st enosis can be congenit al or
development al (e. g. , achondroplasia, mucopolysaccharidosis) or acquired, t hat
is, spondylolit ic, t raumat ic, ost eoporot ic skelet al (e. g. , Paget 's disease of
bone), iat rogenic (e. g. , post surgical), or due t o degenerat ive spondylolist hesis.
Pat ient s develop unilat eral or bilat eral, asymmet ric pain in t he but t ock, t high, or
leg and occasionally neurologic signs (e. g. , numbness, loss of ref lexes, or
paresis) af t er exert ion. Coughing, sneezing, and st raining rarely aggravat e t he
pain. I nt erest ingly, t he st raight leg-raising t est result is of t en negat ive. These
signs and sympt oms are relieved by rest , f lexion at t he w aist , and sit t ing, and
are t hought t o be because of int ermit t ent cauda equina ischemia brought on by
t he increased blood f low demand due t o exercise. This syndrome must be
diff erent iat ed f rom int ermit t ent leg claudicat ion due t o aort oiliac occlusive
disease (Table 4-2). Lumbar spinal st enosis may cause unprovoked erect ions
(spont aneous priapism) w hen w alking[1] and may also be associat ed w it h
rest less legs syndrome in t he elderly (Vesper's curse)[ 11] .
TABLE 4-2 Differential of Neurogenic from Vascular

Claudications
Clinical Neurogenic Vascular

Manifestations Claudications Claudications
Yes, usually
Exertional pain thigh and Yes, usually calf
buttock
Exercise
Variable Constant
tolerance
Reproduces
Effect of bicycle No effect
symptoms
W orse
Effect of incline W orse walking up
walking down
Effect of Reproduces
No effect
standing symptoms
W eakness with Present at

Absent
exertion times
Paresthesias
Uncommon Rare
with exertion
Symptoms with
Reproduces
back symptoms None
hyperextension
Sitting, Stopping activity,

Actions needed
leaning independent of
for relief
forward position
Using
Preventative
shopping cart W alking slower
measures
to lean on
Variable (5–
Time for relief Prompt (15–16 sec)
15 min)
Peripheral Absent at rest or

Preserved
pulses after exercise
W eakness after
Present often No
exercise
Sensory findings
Occasionally No
after exercise
Decrease in
reflexes after Occasionally No
exercise
source: Personal communication. W. Neith Folger, M.D.
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in acquired immune def iciency syndrome. Neurol ogy 1987; 37: 557–561.
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9. Jabre JF, Bryan RW. Bent -knee pulling in t he diagnosis of upper lumbar
root lesions. Arch Neurol 1982; 39: 669–670.
10. Kikt a DG , Breuer AC, Wilbourn AJ. Thoracic root pain in diabet es: t he
spect rum of clinical and elect romyographic f indings. Ann Neurol 1982; 11: 80–
85.
11. LaBan MM, Viola SL, Femminineo AF, et al. Rest less legs syndrome
associat ed w it h diminished cardiopulmonary compliance and lumbar spinal
st enosis—a mot or concomit ant of “Vesper's curse”. Arch Phys Med Rehabi l
1990; 71: 384–388.
12. Lance JW. The red ear syndrome. Neurol ogy 1996; 47: 617–620.
13. Levin KH. Neurologic manif est at ions of compressive radiculopat hy of t he

f irst t horacic root . Neurol ogy 1999; 53: 1149–1151.
14. Levin KH, Maggiano HJ, Wilbourn AJ. Cervical radiculopat hies:
comparison of surgical and EMG localizat ion of single-root lesions. Neurol ogy
1996; 46: 1022–1025.
15. Marinacci AA. A correlat ion bet w een operat ive f indings in cervical
herniat ed disc w it h t he elect romyograms and opaque myelograms.
El ectromyography 1966; 6: 5–23.
16. Mat t le HP, Hess CW, Ludin HP, et al. I solat ed muscle hypert rophy as a
sign of radicular or peripheral nerve injury. J Neurol Neurosurg Psychi atry
1991; 54: 325–329.
17. Mielke U, Ricker K, Emser W, et al. Unilat eral calf enlargement f ollow ing
S1 radiculopat hy. Muscl e Nerve 1982; 5: 434–438.
18. Miller RF, Fox JD, Thomas P, et al. Acut e lumbosacral polyradiculopat hy
due t o cyt omegalovirus in advanced HI V disease: CSF f indings in 17 pat ient s.
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23. Polet t i CE. Third cervical nerve root and ganglion compression: clinical
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24. Radhakrishnan K, Lit chy WJ, O 'Fallon WM, et al. Epidemiology of cervical
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25. Rainville J, Jouve C, Finno M, et al. Comparison of f our t est s of
quadriceps st rengt h in L3 or L4 radiculopat hies. Spi ne 2003; 28: 2466–2471.
26. Ricker K, Rohkamm R, Moxley RT. Hypert rophy of t he calf w it h S1

radiculopat hy. Arch Neurol 1988; 45: 660–664.
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28. Sat oyoshi E, Doi Y, Kinashit a M. Pseudomyot onia in cervical root lesions
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elect rophysiologic examinat ion in pat ient s w it h radiculopat hies. Muscl e Nerve
1988; 11: 1099–1114.
36. Wilbourn AJ, Aminoff MJ. AAEM Minimonograph #32: t he elect rodiagnost ic
examinat ion in pat ient s w it h radiculopat hies. Muscl e Nerve 1998; 21: 1612–
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> Table of C ontents > C hapter 5 - S pinal C or d
Chapter 5
Spinal Cord
Anatomy of the Spinal Cord

Gross Anatomy and Relationship to Vertebral Levels
The spinal cord[13, 15] ext ends f rom t he level of t he cranial border of t he at las,
w here it is cont inuous w it h t he medulla, t o t he low er border of t he f irst lumbar
vert ebra. During early f et al development , t he spinal cord ext ends t o t he low er
end of t he sacrum, but at birt h it ext ends only as f ar as t he upper border of t he
t hird lumbar vert ebra. At 20 w eeks' gest at ional age, t he conus medul l ari s is at
t he L4–L5 level. By 40 w eeks' gest at ional age or at t erm, t he conus medullaris is
at t he L3 level. By age 2 mont hs, it has reached t he adult L1–L2 level[6] . The
average lengt h of t he spinal cord is 45 cm in t he adult male and 42 t o 43 cm in
t he adult f emale. The corresponding average lengt h of t he spinal column is 70
cm. Cylindrical and f lat t ened in a dorsovent ral direct ion, t he spinal cord
demonst rat es bot h cervical and lumbar enlargement s. The f irst enlargement
corresponds t o t he segment al innervat ion of t he upper ext remit ies and ext ends
f rom t he C5 t o T1 spinal levels, w hereas t he second corresponds t o t he
innervat ion of t he low er ext remit ies and ext ends f rom L3 t o S2. Below t he lumbar
enlargement , t he spinal cord narrow s, ending as t he conus medullaris. From t he
conus medullaris, a f ine pial t hread know n as t he f i l um termi nal e passes dow n t o
t he dorsum of t he f irst coccygeal segment .
Alt hough t he spinal cord is a cont inuous and nonsegment al st ruct ure, t he 31
pairs of nerves originat ing f rom it give it a segment al appearance. O n t his basis,
t he spinal cord is considered t o have 31 segment s analogous t o t he spinal
nerves (8 cervical, 12 t horacic, 5 lumbar, 5 sacral, and 1 coccygeal). O w ing t o
t he diff erent grow t h rat es of t he spinal cord and t he vert ebral column, t he more
caudal (lumbar and sacral) spinal root s must t ravel a considerable dist ance in
t he subarachnoid space bef ore t hey reach t heir corresponding int ervert ebral
f oramina. This low er group of root s congregat es around t he f ilum t erminale in t he
spinal t heca and is know n as t he cauda equi na.
I n t he cervical region, t he spinous process of a part icular vert ebra mat ches t he
level of t he corresponding cord segment ; in t he upper t horacic region, t here is a
discrepancy of t w o segment s (e. g. , t he f ourt h t horacic spinal segment overlies
t he sixt h) and in t he low er t horacic region, t here is a discrepancy of t hree
segment s. The elevent h t horacic spinous process overlies t he t hird lumbar cord
segment , and t he t w elf t h overlies t he f irst sacral cord segment .
The ext ernal surf ace of t he spinal cord is marked by a ventral medi an f i ssure
and a dorsal median sulcus (cont inued by a dorsal median sept um), w hich divide
t he cord int o t w o symmet ric halves. I n t he post erolat eral surf ace, t here is a
dorsol ateral sul cus marking t he ent rance of t he dorsal root s. I n t he ant erolat eral
surf ace, t here is a ventrol ateral sul cus t hat is not as w ell delineat ed as t he
ot her sulci because t he vent ral root s emerge as a number of separat e t w igs.
Cross-Sectional Anatomy of the Spinal Cord

I n it s cross sect ion (Fig. 5-1), t he spinal cord consist s of t he cent rally placed
gray mat t er surrounded by w hit e mat t er. The gray mat t er is shaped like a
modif ied H, w it h t w o lat eral columns joined by a t ransverse commissure. Each
lat eral column has a dorsal horn lying dorsolat erally and a ventral horn lying
vent rolat erally. The cent ral
canal of t he spinal cord is locat ed in t he cent er of t he gray commissure.
FI G URE 5-1 Anat omy of t he spinal cord (cross sect ion). Tract laminat ion: S
= sacral segment s; L = l umbar segment s; Th = thoraci c segment s; C =
cervi cal segment s
I n addit ion t o t hese gray columns, t here is an i ntermedi ol ateral gray col umn t hat
ext ends f rom segment s T1 t hrough L2 and gives rise t o preganglionic
sympat het ic aut onomic f ibers. There is also an int ermediolat eral zone of gray
mat t er in t he second, t hird, and f ourt h sacral segment s, w hich is t he source of
t he sacral port ion of t he parasympat het ic out f low. A laminar archit ect ure of nine
cell layers or laminae is dist inguishable w it hin t he gray mat t er: laminae I t hrough
VI (dorsal horn), lamina VI I (int ermediat e zone), and laminae VI I I and I X (vent ral
horn). The zone of Li ssauer (post erolat eral t ract of Lissauer) separat es t he
dorsal gray column f rom t he surf ace of t he spinal cord. The port ion of t he gray
mat t er dorsal t o t he cent ral canal is t he dorsal gray commi ssure and t hat of t he
vent ral port ion is t he ventral gray commi ssure.
LAMINA
I Nucleus post eromarginalis

I I Subst ant ia gelat inosa
I I I and I V Nucleus proprius dorsalis
V Zone ant erior t o lamina I V
VI Zone at t he base of dorsal horn
VI I I nt ermediat e zone
VI I I Zone in t he vent ral horn (rest rict ed t o medial aspect in cervical and
lumbar enlargement s)
I X Medial and lat eral ant erior horn cell columns.
Each half of t he w hit e mat t er of t he spinal cord is separat ed int o t hree f uniculi
by t he gray mat t er and t he int ramedullary port ions of t he spinal root s, as
f ollow s:
1. The dorsal f uniculus: t he port ion of w hit e mat t er bet w een t he dorsomedian
and t he dorsolat eral sulci
2. The lat eral f uniculus: t he w hit e mat t er bet w een t he dorsolat eral and t he
vent rolat eral sulci
3. The vent ral f uniculus: t he w hit e mat t er bet w een t he vent rolat eral sulcus and
t he vent romedian f issure
Bands of w hit e mat t er know n as t he dorsal and ventral whi te commi ssures
correlat e w it h t he gray commissure. The w hit e mat t er comprises ascending and
descending t ract s.
Major Ascending and Descending Tracts of the Spinal

Cord
Ascending Tracts
Almost all t he sensory aff erent input t o t he spinal cord ent ers by w ay of t he
dorsal root s. The cent ral end of a dorsal root split s int o lat eral and medial
bundles. The f inely myelinat ed or unmyelinat ed f ibers of t he lat eral bundle
bif urcat e int o short ascending and descending branches w it hin t he zone of
Lissauer and t erminat e on t he neurons of t he dorsal horn. The axons of second-
order neurons, w it h cell bodies presumably in laminae VI and VI I , decussat e over
several segment s by w ay of t he vent ral w hit e commissure; t hey proceed t o t he
vent rolat eral quadrant of t he spinal
cord and ascend as t he l ateral spi nothal ami c ( neospi nothal ami c) tract t o reach
t he t halamus (vent ral post erolat eral nucleus). These f ibers convey pain and
t emperat ure sensat ion and have a laminar conf igurat ion. As a consequence of
t his arrangement , f ibers carrying inf ormat ion f rom cervical regions lie
dorsomedially and t hose f rom sacral regions lie vent rolat erally. There also
seems t o be a segregat ion bet w een pain and t emperat ure f ibers, w it h f ibers
carrying t emperat ure inf ormat ion locat ed dorsolat erally t o pain-carrying ones.
Pain may also be conduct ed by w ay of t he spi noreti cul othal ami c
(paleospinot halamic) syst em. Fibers f rom t his syst em have short axons t hat
synapse in t he brainst em ret icular f ormat ion and termi nate in t he int ralaminar
nuclei of t he t halamus. The lat eral spinot halamic t ract conveys inf ormat ion t hat is
perceived as sharp and localized pain, w hereas t he spinoret iculot halamic syst em
is concerned w it h poorly localized pain sensat ion.
Fibers carrying t act ile sensibilit y (light t ouch) also bif urcat e af t er ent ering t he
zone of Lissauer and t erminat e w it h int erneurons of t he dorsal horn. The axons
of second-order neurons, w hose cell bodies presumably lie in laminae VI and VI I ,
cross over t o t he opposit e side t hrough t he vent ral w hit e commissure and ascend
as t he ventral spi nothal ami c tract t o reach t he vent ral post erolat eral nucleus of
t he t halamus. Light t ouch is also t ransmit t ed by w ay of t he dorsal f uniculus–
medial lemniscus pat hw ay.
The heavily myelinat ed f ibers of t he medial bundle of t he dorsal root pass over
t he dorsal horn int o t he dorsal f uniculus. Af t er giving rise t o collat erals, w hich
t erminat e largely in laminae I I I and I V, t hey ascend in t he dorsal f uniculus. The
f ibers f rom t he low ermost part of t he body (sacral, lumbar, and low er six
t horacic levels) are locat ed more medially and const it ut e t he f asci cul us graci l i s,
w hereas t hose coming f rom t he upper part of t he body (upper six t horacic and all
cervical levels) occupy a more lat eral posit ion and const it ut e t he f asci cul us
cuneatus. The f asciculus gracilis ends in t he nucleus gracilis of t he medulla; t he
f asciculus cuneat us also reaches t he dorsal surf ace of t he medulla and
t erminat es in t he nucleus cuneat us. The axons of t hese t w o nuclei decussat e in
t he low er medulla and ascend as t he medial lemniscus t o reach t he vent ral
post erolat eral nucleus of t he t halamus. These f ibers carry inf ormat ion concerning
discriminat ive senses (posit ion sense, vibrat ion sense, w eight percept ion,
discriminat ive t ouch, pressure t ouch, t w o-point discriminat ion, st ereognosis, and
shape and movement aw areness). O t her ascending t ract s include t he dorsal
spi nocerebel l ar and ventral spi nocerebel l ar tracts, w hich t ransmit unconscious
propriocept ive inf ormat ion f rom t he low er limbs and t he inf erior half of t he body
t o t he cerebellum and t he cuneocerebel l ar and rostrocerebel l ar tracts, w hich
convey similar inf ormat ion f rom t he upper limbs and rost ral half of t he body.
Descending Tracts
Five descending syst ems exert t onic eff ect s on t he α and γ mot or neurons; t hese
syst ems are t heref ore import ant in t he post ural cont rol of t he limbs. Tw o of
t hese syst ems (t he vesti bul ospi nal tract and t he medi al reti cul ospi nal tract) t end
t o f acilit at e t he α and γ mot or neurons of ant igravit y muscles and t he ot her t hree
syst ems (t he corti cospi nal tract, t he corti corubrospi nal tract, and t he l ateral
reti cul ospi nal tract) inhibit t he ant igravit y muscles and f acilit at e t he ant agonist s.
Corticospinal Tract
The f ibers of t he cort icospinal pat hw ay arise mainly f rom somat ot opically
organized areas f rom t he primary mot or cort ex, lat eral premot or cort ex, and
supplement ary mot or cort ex of t he cont ralat eral hemisphere. The cort icospinal
neurons are f ound primarily in Brodmann's area 4, w hich occupies t he post erior
port ion of t he precentral gyrus ( pri mary motor cortex or MI). The lat eral
premot or and supplement ary mot or cort ices are locat ed in Brodmann's area 6.
Cort icospinal axons also arise f rom neurons in t he primary sensory cort ex in t he
postcentral gyrus (Brodmann's areas 3, 1, and 2), anteri or paracentral gyri ,
superi or pari etal l obul e (Brodmann's areas 5 and 7), and port ions of t he
ci ngul ate gyrus on t he medial surf ace of t he hemisphere. These f ibers descend
t hrough t he corona radiat a, t he post erior limb of t he int ernal capsule, and t he
vent ral port ion of t he mesencephalon and pons dow n t o t he vent ral port ion of t he
medulla, w here t hey f orm t w o large pyramids. When t hey reach t he caudal
port ion of t he medulla, approximat ely 90% of t he 1 million f ibers of each pyramid
cross over in an int erdigit at ed f ashion t o descend in a massive t ract in t he lat eral
f uniculus of t he spinal cord know n as t he l ateral corti cospi nal tract. The f ibers in
t he lat eral cort icospinal t ract ext end all t he w ay t hrough t he spinal cord and
t erminat e in laminae I V t hrough VI I and I X. The ot her 10% of t he f ibers t hat do
not decussat e descend in t he ipsilat eral vent ral f uniculus as t he ventral
corti cospi nal tract, w hich t erminat es (af t er crossing in t he vent ral w hit e
commissure) in lamina VI I I of t he cervical and upper t horacic regions.
Mot or neurons t hat innervat e t he axial musculat ure are sit uat ed in an ext reme
vent romedial sect or of lamina I X, w hereas t hose t hat innervat e t he int rinsic
ext remit y musculat ure are clust ered w it hin a dorsolat eral sect or; mot or neurons
f or t he limb girdle musculat ure are locat ed in an int ermediat e posit ion[2] . This
vent romedial–dorsolat eral gradient of t he proximal–dist al represent at ion is also
maint ained w it hin t he int ermediat e zone (laminae V–VI I I ), w hich cont ains t he
propriospinal neurons. Propriospinal neurons project ing t o t he limb and axial
mot or neurons t end t o project f or considerable dist ances above and below t he
segment of origin, t hereby inf luencing large groups of proximal muscles. By
cont rast , propriospinal neurons project ing t o mot or neurons t hat innervat e t he
int rinsic muscles of t he limb t end t o project only short dist ances above and
below t he segment of origin, t hereby inf luencing smaller, more rest rict ed groups
of dist al muscles[2] .
Corticorubrospinal Tract
Cells in cort ical areas 4 and 6 and 1, 2, and 3 project t o t he ipsilat eral red
nucleus. The axons of some of t hese rubral cells decussat e and descend t hrough
t he brainst em t egment um and lat eral f uniculus of t he spinal cord as t he
rubrospi nal tract.
Lateral Reticulospinal Tract

This t ract originat es in t he medullary ret icular f ormat ion, chief ly on t he ipsilat eral
side, and descends in t he vent rolat eral f uniculus.
Vestibulospinal Tract
Fibers originat ing in t he lat eral vest ibular nucleus ext end t hrough t he ent ire
lengt h of t he spinal cord in t he ant erior region of t he lat eral f uniculus. Fibers
f rom t he medial vest ibular nucleus ext end t hrough t he cervical and upper t horacic
levels in t he vent ral f uniculus.
FI G URE 5-2 The vascular supply of t he spinal cord
Medial Reticulospinal Tract

This pat hw ay originat es in t he pont ine and lat eral medullary ret icular f ormat ions
and descends largely uncrossed in t he vent ral f uniculus of t he spinal cord.
Arterial Supply to the Spinal Cord
The vascular supply of t he spinal cord (Fig. 5-2) is divided int o ext raspinal and
int raspinal syst ems[28, 96] .
Extraspinal System (Extramedullary Arteries)

The lat eral spinal art eries, present in early development , give rise t o radicular
art eries, radiculopial art eries, and radiculomedullary art eries. The lat t er, by
means of t he ant erior and post erior spinal art eries, are responsible f or most of
t he blood supply t o t he spinal cord. The radiculomedullary art eries are present
only at cert ain segment al levels. Approximat ely 6 t o 10 of t hem join t he ant erior
spinal art ery, running along t he ant erior median f issure, and 10 t o 23 join t he
post erior spinal art eries. The ant erior spinal art ery arises f rom t he anast omosis
of t w o branches f rom t he vert ebral art ery, ext ends f rom t he level of t he olivary
nucleus t o t he t ip of t he conus medullaris, and supplies t he vent ral surf ace of t he
medulla and t he ant erior t w o-t hirds
of t he spinal cord. Sulcal branches of t he anteri or spi nal artery supply t he

ant erior horn, t he lat eral horn, t he cent ral gray mat t er, and t he basal aspect of
t he post erior horn. The posteri or spi nal arteri es are paired branches of t he
int racranial vert ebral art ery or t he post erior inf erior cerebellar art ery. The
post erior spinal art eries also ext end t he lengt h of t he cord and supply t he
post erior horn and t he post erior f uniculus. This art erial syst em receives 10 t o 20
post erior radicular vessels[28, 96] . At t he conus medullaris, t he ant erior and
post erior spinal art eries are joined by t he anast omosing ansa of t he conus.
Anast omot ic radicular art eries, most of t hem branches of t he aort a, f eed bot h
t he art erial syst ems at various levels.
Three main f unct ional regions in t he vert ical axis of t he spinal cord have been
dist inguished according t o t heir unequal blood supply:
1. The upper or cervi cothoraci c regi on, richly vascularized, embraces t he

cervical and f irst t w o t horacic cord segment s. The f irst f our cervical
segment s are supplied by t he ant erior spinal art ery and have limit ed or no
radiculomedullary supply. The low er f our cervical and t he f irst t w o t horacic
segment s receive t heir supply f rom t w o t o f our large radicular art eries
arising f rom t he vert ebral and t he ascending and deep cervical art eries. The
most import ant of t hese radicular art eries is named t he artery of the cervi cal
enl argement typi cal l y ari si ng between C4 and C8; it usually ent ers t he spinal
cord w it h t he sevent h and eight h cervical root s. A variable number of
radiculomedullary vessels f eed t he post erior spinal art eries, and t hey
predominat e in t he cervical enlargement .
2. The i ntermedi ate or mi dthoraci c regi on, poorly vascularized, is supplied by
t he branches of t he int ercost al art eries and includes t he t hird t hrough t he
eight h t horacic segment s. I t receives a single radiculomedullary art ery, w hich
ent ers w it h t he sixt h, sevent h, or eight h t horacic root s. There are t w o t o
t hree segment al f eeders t o t he post erior spinal art eries.
3. The l ower or thoracol umbosacral regi on enjoys a rich vascularizat ion and is
nourished by radiculomedullary branches of t he int ercost al and lumbar
art eries. The most import ant source of supply t o t he ant erior circulat ion
depends on t he great anteri or radi cul ar artery of Adamki ewi cz ( artery of the
l umbar enl argement) t hat ent ers most f requent ly f rom t he lef t side w it h t he
nint h, t ent h, elevent h, or t w elf t h t horacic or f irst t w o lumbar root s, seldom
f rom t he lumbar region or higher segment s bet w een T6 and T8. Numerous
post erior radicular art eries are also present in t his region.
Intraspinal System (Intramedullary Arteries)

Branches of t he ant erior and post erior spinal art eries f orm a perimedullary
circuit ry around t he cord. Branches arise f rom t his plexus t o supply a subst ant ial
amount of w hit e mat t er and t he dorsal horns of t he gray mat t er. The art erial
supply of t he gray mat t er is richer t han t hat of t he w hit e mat t er. The largest
branches of t he ant erior spinal art ery (sulcocommissural art eries) ent er t he
vent ral median f issure and supply t he gray mat t er, except f or t he dorsal horns
and t he innermost port ion of t he w hit e mat t er. The dorsal horns and f uniculi are
supplied by t he paired post erior spinal art eries, t he post erior medullary f eeders,
and t he perf orat ing pial branches.
Lesions of the Spinal Cord

Complete Spinal Cord Transection (Transverse
Myelopathy)
Wit h complet e cord t ransect ion (Fig. 5-3), all ascending t ract s f rom below t he
level of t he lesion and all descending t ract s f rom above t he level of t he lesion
are int errupt ed [7, 32, 45] . Theref ore, all mot or and sensory f unct ions below t he
level of spinal cord damage are dist urbed. More of t en, t he sect ion is incomplet e
and irregular, and t he f indings ref lect t he ext ent of t he damage. Transverse
myelopat hy of acut e onset is of t en due t o t raumat ic spine injuries, t umor (e. g. ,
met ast at ic carcinoma, lymphoma), mult iple sclerosis, or vascular disorders.
O t her causes include spinal epidural hemat oma (usually secondary t o
ant icoagulant s) or abscess, paraneoplast ic myelopat hy, aut oimmune disorders,
herniat ed int ervert ebral disc, and parainf ect ious or post vaccinal syndromes[45] .
All sensory modalit ies (sof t t ouch, posit ion sense, vibrat ion, t emperat ure, and
pain) are impaired below t he level of t he lesion. Clinically, pinprick loss below a
segment al level is most valuable in localizing t he lesion. A sensory level may be
easily missed unless caref ully, and somet imes repeat edly, sought . I n complet e
lesions, part icularly w it h ext ramedullary pat hology, t he sensory level may be
many segment s below t he level of t he lesion. For inst ance, high t horacic lesions
may present w it h levels in t he upper lumbar segment s. The somat ot opic
dist ribut ion of f ibers in t he lat eral spinot halamic t ract , w it h t he low est segment s
represent ed more superf icially, has been invoked t o explain t his apparent
discrepancy. More reliable band-like radicular pain or segment al parest hesias
may occur at t he level of t he lesion and may be of localizing value f or t he
appropriat e spinal level. I f t he pain is cervical, it radiat es t o t he arms; if t horacic
in origin, it is circumf erent ial t o t he chest or abdomen; and if lumbar or sacral, it
radiat es t o t he legs. Localized vert ebral pain (over t he vert ebral spinous
process), w hich is accent uat ed by palpat ion or vert ebral percussion, may occur
w it h dest ruct ive lesions (especially inf ect ions and
t umors) and may also be of localizing value. Pain t hat is w orse w hen recumbent
and bet t er w hen sit t ing or st anding is common w it h malignancy.
FI G URE 5-3 Spinal cord syndromes
Def ect s in pain and t emperat ure sensat ion below a cert ain level in t he t runk are
almost alw ays a sign of spinal cord disease. How ever, because of t he
somat ot opic organizat ion of sensory f ibers in t he spinot halamic t ract at higher
levels, rarely a lat eral medullary or lat eral pont ine lesion may cause a sensory
def icit in t he cont ralat eral leg, t runk, or bot h t o a specif ic level[59] . For
example, a very lat erally placed medullary lesion may damage t he sacral and
lumbar aff erent f ibers of t he lat eral spinot halamic t ract but spare t he more
medial t horacic and cervical aff erent f ibers, result ing in a sensory loss below a
specif ic lumbar level. A similar sensory level described w it h a pariet al lesion is
even more unusual[19] .
M otor Disturbances
Paraplegia (loss of low er limb mot or f unct ion) or t et raplegia (loss of mot or
f unct ion in all f our ext remit ies) occurs below t he level of t he lesion ow ing t o an
int errupt ion of t he descending cort icospinal t ract s. I nit ially, especially w it h acut e
lesions, t he paralysis is f laccid and aref lexic because of spinal shock.
Event ually, hypert onic, hyperref lexic paraplegia or t et raplegia occurs w it h
bilat eral ext ensor t oe signs, loss of superf icial abdominal and cremast eric
ref lexes, and ext ensor and f lexor spasms. Ext ension at t he hip and knee occurs
w it h incomplet e or high spinal cord lesions, w hereas f lexion at t he hip and t he
knee occurs w it h complet e and low er lesions of t he spinal cord.
At t he level of t he lesion, t here are low er mot or neuron signs (paresis, at rophy,
f asciculat ions, and aref lexia) in a segment al dist ribut ion because of damage t o
t he ant erior horn cells or t heir vent ral root s. These low er mot or neuron signs,
w hich may be quit e subt le in t horacic lesions, localize t he lesion t o a specif ic
spinal cord level.
Autonomic Disturbances
Urinary and rect al sphinct er dysf unct ion w it h incont inence may occur w it h
t ransverse myelopat hy. Urgency of mict urit ion is t he usual bladder sympt om, w it h
urinary ret ent ion a lat er problem, and incont inence not seen unt il very lat e.
Const ipat ion is t he most common bow el sympt om. I nit ially, at onic and, lat er,
spast ic rect al and bladder sphinct er dysf unct ion occur w it h lesions at any spinal
level. Bladder and bow el dysf unct ion result f rom bilat eral lesions, w hich may
also cause ort host at ic hypot ension. Anhidrosis, t rophic skin changes, impaired
t emperat ure cont rol, and vasomot or inst abilit y are seen below t he level of t he
lesion. Sexual dysf unct ion (especially impot ence) may be present . A lesion
involving t he cell bodies of t he preganglionic sympat het ic neuron locat ed in t he
cervicot horacic cord may result in an ipsilat eral Horner syndrome.
Hemisection of the Spinal Cord (Brown-Séquard

Syndrome)
Funct ionalquard syndrome hemisect ion of t he spinal cord result s in a
charact erist ic syndrome (t he Brow n-Séquard syndrome, Fig. 5-3)[ 49] , w hich
consist s of t he f ollow ing signs and sympt oms:
1. Loss of pai n and temperature sensati on contral ateral to the hemi secti on due
to i nterrupti on of the crossed spi nothal ami c tract. This sensory level is
usually one or t w o segment s below t he level of t he lesion.
2. Ipsi l ateral l oss of propri ocepti ve f uncti on bel ow the l evel of the l esi on due
to i nterrupti on of the ascendi ng f i bers i n the posteri or col umns. Tact ile
sensat ion may be normal or minimally decreased. This vibrat ory and posit ion
sense loss may be relat ed more t o t he int errupt ion of t he dorsal
spinocerebellar t ract t han t o t he damage of t he post erior columns per
se[ 73] .
3. Ipsi l ateral spasti c weakness due to i nterrupti on of the descendi ng
corti cospi nal tract segmental l ower motor neuron and sensory si gns at the
l evel of the l esi on due to damage of the roots and anteri or horn cel l s at thi s
l evel . The Brow n-Séquard syndrome is charact erist ically produced by
ext ramedullary lesions.
Lesions Affecting the Spinal Cord Centrally

The cent ral spinal cord syndrome is best exemplif ied by syringomyelia,
hydromyelia, hemat omyelia, and int ramedullary cord t umors. The clinical course
of syringomyelia is usually slow ly progressive, and t he syrinx rarely remains
limit ed. O f t en t he condit ion is associat ed w it h hindbrain abnormalit ies as seen in
Chiari t ype I and t ype I I or Dandy-Walker malf ormat ions, or as a lat e sequel t o
t raumat ic paraplegia or t et raplegia, spinal t rauma, spinal cord t umors,
arachnoidit is or, rarely, w it h myelit is[74] . Acut e at ypical present at ions are rarely
seen[ 4] . Spinal cord damage st art s cent rally and spreads cent rif ugally t o involve
ot her spinal cord st ruct ures. Charact erist ically, t he decussat ing f ibers of t he
spinot halamic t ract conveying pain and t emperat ure sensat ion are compromised
init ially. This result s in t hermoanest hesia and analgesia in a “vest -like” or
“suspended” bilat eral dist ribut ion w it h t he preservat ion of sof t
t ouch sensat ion and propriocept ion (di ssoci ati on of sensory l oss). Wit h f orw ard
ext ension of t he disease process, t he ant erior horn cells become involved at t he
level of t he lesion, result ing in segment al neurogenic at rophy, paresis, and
aref lexia. Lat eral ext ension result s in an ipsilat eral Horner syndrome (ow ing t o
t he involvement of t he ciliospinal cent er of Budge w it h C8–T2 lesions),
kyphoscoliosis (ow ing t o t he involvement of t he dorsomedian and vent romedian
mot or nuclei supplying t he paraspinal muscles), and, event ually, spast ic paralysis
below t he level of t he lesion (ow ing t o t he cort icospinal t ract involvement ).
Dorsal ext ension disrupt s dorsal column f unct ion (ipsilat eral posit ion sense and
vibrat ory loss), and w it h ext reme vent rolat eral ext ension, t he spinot halamic t ract
is aff ect ed, producing t hermoanest hesia and analgesia below t he spinal level of
t he lesion. Because of t he laminat ion of t he spinot halamic t ract (dorsomedial
cervical sensat ion and vent rolat eral sacral sensat ion), sacral sensat ion is spared
(sacral spari ng) by int raparenchymal lesions. Syringomyelia may also
occasionally cause a neuropat hic art hropat hy of t he shoulder, elbow, and ot her
joint s[ 87] . Pain is present in approximat ely half of t he pat ient s. The f act t hat t he
init ial manif est at ion of syringomyelia may be a neuropat hic art hropat hy is of
major clinical import ance[7] .
An acut e cervical cent ral spinal cord syndrome can occur af t er severe
hyperext ension injuries of t he neck[80] . Pat ient s w it h t his syndrome become
quadriplegic af t er cervical t rauma but regain st rengt h in t he legs in a mat t er of
hours or even minut es. There is bladder dysf unct ion, usually urinary ret ent ion,
and pat chy sensory loss below t he level of t he lesion. Weakness is more
pronounced in t he arms, more dist al t han proximal (“man-in-a-barrel syndrome”).
Considerable recovery is common. This syndrome is probably due t o t he damage
t o t he cent ral gray mat t er and lat eral cort icospinal t ract at t he cervical spinal
cord enlargement .
Posterolateral Column Disease

The post erior and lat eral columns in t he upper spinal cord may be select ively
damaged in subacut e combined degenerat ion of t he spinal cord ow ing t o vit amin
B 12 (cobalamin) def iciency[40] . Post erior and lat eral spinal cord involvement is
also seen in cases of vacuolar myelopat hy associat ed w it h acquired
immunodef iciency syndrome (AI DS), human T-lymphot ropic virus t ype 1 (HTLV-1),
associat ed myelopat hy (t ropical spast ic paraparesis), or ext rinsic cord
compression (e. g. , cervical spondylosis). Pat hologic changes in cases of
subacut e combined degenerat ion predominant ly involve t he cervical cord,
alt hough changes may ext end t o t he t horacic and lumbar cord regions. Most
pat ient s w it h subacut e combined degenerat ion complain of parest hesias in t he
f eet and, less of t en, in t he hands, diff icult ies w it h gait and balance, and have
signs of dorsal column dysf unct ion, including loss of propriocept ion and vibrat ion
sense in t he legs as w ell as sensory at axia w it h a posit ive Romberg's sign and
bladder at ony. Pain and t emperat ure sensat ions remain int act because of t he
preservat ion of t he spinot halamic t ract s. Bilat eral cort icospinal t ract dysf unct ion
result s in spast icit y, hyperref lexia, and bilat eral Babinski's signs. How ever,
ref lexes may be lost or hypoact ive because of superimposed peripheral
neuropat hy. AI DS-associat ed vacuolar myelopat hy f requent ly present s lat e in t he
course of HI V disease. Pat ient s usually have a slow ly progressive spast ic
paraparesis, sensory at axia w it h impaired vibrat ion and posit ion sense, normal
cobalamin and f olat e levels, and increased cerebrospinal f luid (CSF) prot ein w it h
pleocyt osis. There may be associat ed dement ia and a spast ic bladder[93] .
Findings commonly encount ered w it h HTLV-1–associat ed myelopat hy include
backache, leg parest hesias, urinary f requency, a slow ly progressive
paraparesis, muscle st ret ch hyperref lexia, Babinski's signs, and impaired
vibrat ory and posit ion sense. CSF show s lymphocyt ic pleocyt osis, elevat ed CSF
prot ein, normal glucose cont ent , and increased CSF I gG w it h ant ibodies t o
HTLV-1. A chronic progressive spast ic–at axic gait w it h propriocept ive def icit s
has also been described in copper def iciency myelopat hy (copper def iciency
myeloneuropat hy). Pat ient s of t en exhibit anemia, neut ropenia, and persist ent ly
increased serum zinc levels [36, 50, 51, 52, 69, 76, 79] .
Posterior Column Disease

The post erior columns are select ively damaged by tabes dorsal i s (t abet ic
neurosyphilis, progressive locomot or at axia). I nf lammat ion and degenerat ion of
t he dorsal root s cause secondary dest ruct ion of t he post erior columns of t he
spinal cord. Tabes usually develops 10 t o 20 years af t er t he onset of luet ic
inf ect ion and result s in impaired vibrat ion and posit ion sense and decreased
t act ile localizat ion. Post erior column dysf unct ion also result s in labilit y of
mechanical sensat ion t hreshold, t act ile and post ural hallucinat ions, persist ence
of mechanorecept or sensat ion, and dist urbances in t he know ledge of ext remit y
movement and posit ion (t emporal and spat ial dist urbances)[ 64] . There is sensory
at axia, not ed f irst at night or in t he dark, and a posit ive Romberg's sign.
O w ing t o propriocept ive int errupt ion, t he gait is at axic, and “st omping” or
“double t apping” is charact erist ic. The gait disorder is much more pronounced in
darkness or w it h eye closure because visual cues can no longer be incorporat ed
in maint aining balance. O f t en pat ient s f all f orw ard immediat ely f ollow ing eye
closure (posit ive “sink” sign). Pat ient s w it h t abes dorsalis of t en complain of
lancinat ing (light ning) pains, most f requent ly in t he legs, develop urinary
incont inence, and have absent pat ellar and ankle muscle st ret ch ref lexes. The
aff ect ed limbs are hypot onic but not w eak, and hyperext ensible joint s are
common. Abdominal crises, mimicking a surgical abdomen, occur in
approximat ely 10% of pat ient s. Laryngeal crises w it h st ridor, rect al, and vesical
crises are less common. Trophic dist urbances result in Charcot joint s, w hich are
analgesic joint s t hat disint egrat e and become def ormed as a result of chronic
t rauma. Many pat ient s have diminished deep pain sensat ion demonst rat ed by
diminished sensat ion t o squeezing t he Achilles t endon (Abadie's sign). O f t en,
t here is impaired light t ouch percept ion in t he Hit zig zones (e. g. , t he cent ral area
of t he f ace, t he nipple area, t he ulnar borders of t he arms, t he peroneal borders
of t he legs, and t he perianal area). Many pat ient s w it h t abes dorsalis also have
small, miot ic, and irregular pupils, unreact ive t o light , but normally react ive t o
accommodat ion (Argyll Robert son pupils), opt ic at rophy, eyelid pt osis, or
opht halmoplegia. Wit h dysf unct ion of t he post erior columns in t he cervical region,
neck f lexion may elicit a sudden “elect ric-like” sensat ion dow n t he back or int o
t he arms (Lhermi tte's si gn or “barber's chair” syndrome). This sign, alt hough
usually regarded as t ypical of mult iple sclerosis, can also occur w it h
compressive lesions (e. g. , cervical spondylosis) or af t er cervical cord radiat ion.
I t is t hought t o be due t o increased mechanosensit ivit y of t he dorsal columns,
w it h neck f lexion inducing increased f iring rat es of spont aneously act ive sensory
unit s and recruit ment of previously silent unit s[86] .
Truncal and gait at axia may occur w it h spinal cord lesions (e. g. , met ast at ic
t umor causing cord compression) w it hout associat ed propriocept ive diff icult ies
(e. g. , t he heel-t o-shin t est is normal) [30] . This t runcal at axia may be due t o
impaired conduct ion in t he dorsal spinocerebellar t ract and subsequent
mismat ched vermal int egrat ion of vent ral spinocerebellar t ract inf ormat ion (copy
of eff erent cent ral inst ruct ion) and dorsal spinocerebellar t ract inf ormat ion
(aff erent t runcal f eedback)[ 30] .
Pat ient s may present w it h at axia as t he primary manif est at ion of epidural spinal
cord compression [33] . I n t hese pat ient s, low er ext remit y dysmet ria, gait at axia,
or bot h may be t he only neurologic signs; pat ient s usually have t horacic spine
compression, suggest ing possible select ive vulnerabilit y of t he spinocerebellar
t ract s in t he t horacic spine t o compressive ischemia[33] .
Anterior Horn Cell Syndromes

Cert ain disease processes select ively damage t he ant erior horn cells of t he
spinal cord[99] . The cranial mot or nuclei may also be involved. This diff use
ant erior horn cell involvement is best exemplif ied by t he aut osomal recessive
spinal muscular at rophies, including (a) t ype I inf ant ile progressive spinal
muscular at rophy of Werdnig-Hoff man disease, (b) int ermediat e spinal muscular
at rophy or t ype I I spinal muscular at rophy, (c) t ype I I I juvenile progressive spinal
muscular at rophy or Kugelberg-Welander disease, and (d) progressive spinal
muscular at rophy in mot or neuron disease. Adult onset of spinal muscular
at rophy may involve t he proximal or dist al musculat ure or have a chronic
asymmet ric monomelic pat t ern. Pure low er mot or neuron syndromes have been
described in cases of hexosaminidase def iciency, poliomyelit is (post polio
syndrome), and post irradiat ion syndrome.
When diff use ant erior horn cell damage occurs, diff use w eakness, at rophy, and
f asciculat ions are not ed in t he muscles of t he t runk and ext remit ies. Muscle t one
is usually reduced and muscle st ret ch ref lexes may be depressed or absent .
Sensory changes are absent because t he sensory t ract s remain unaff ect ed. A
variant of mot or neuron disease (Vulpian-Bernhardt syndrome) may present w it h
symmet rical at rophy and w eakness of t he arms, w it h minimal low er ext remit y or
bulbar musculat ure involvement (f lail arm syndrome)[ 38] .
Combined Anterior Horn Cell and Pyramidal Tract

Disease
This syndrome charact erizes amyot rophic lat eral sclerosis (mot or neuron
disease, Charcot 's disease, Lou G ehrig's disease), in w hich degenerat ive
changes occur in t he ant erior horn cells of t he spinal cord (and in t he mot or
nuclei of t he brainst em) and in t he cort icospinal t ract s. Progressive diff use low er
mot or neuron signs (progressive muscular at rophy, paresis, and f asciculat ions)
are superimposed on t he signs and sympt oms of upper mot or neuron dysf unct ion
(paresis, spast icit y, and ext ensor plant ar responses). Virt ually any st riat ed
muscle may be aff ect ed, except t he pelvic f loor
sphinct er[ 44, 57] . Rarely, pat ient s may present w it h ext ernal ocular muscle
abnormalit ies[ 35, 53] . The onset of mot or neuron disease is of t en f ocal or
predominant ly unilat eral[66] , w it h muscle w eakness or at rophy of one hand or
f oot being t he commonest present at ion[46] . Muscle cramps are t he f requent ly
associat ed complaint s. The muscle st ret ch ref lexes may be depressed (ow ing t o
t he low er mot or neuron lesions) but are of t en exaggerat ed, especially in t he
low er ext remit ies, ow ing t o t he concomit ant cort icospinal t ract compromise.
Sensory changes are usually absent , and abdominal superf icial ref lexes are
charact erist ically preserved. Urinary and rect al sphinct ers are unaff ect ed ow ing
t o t he sparing of “X group” cells of O nuf 's nucleus locat ed in t he vent ral margin
of t he ant erior sacral (S2) horns[57, 58] . Bulbar or pseudobulbar impairment is
of t en superimposed, result ing in explosive dysart hria, dysphagia, emot ional
incont inence, and t ongue spast icit y, at rophy, or w eakness. Recent ly proposed
crit eria helpf ul f or clinical t rials def ine t he f ollow ing diagnost ic cat egories:
clinically def init e, clinically probable—laborat ory support ed, and clinically
possible[ 94] .
The marked het erogeneit y of mot or neuron disorders is best exemplif ied by t he
recent World Federat ion of Neurology classif icat ion, w hich includes 28 aut osomal
dominant syndromes, 37 aut osomal recessive syndromes, and 16 diff erent t ypes
of mot or neuron disorders/ dement ia syndromes[54] . O f t hese, X-linked recessive
spinal bulbar muscular at rophy, also know n as Kennedy's di sease (X-linked
bulbospinal neuronopat hy), caused by an expansion of a normal CAG repeat
w it hin t he f irst exon of t he androgen recept or gene, is of paramount diagnost ic
import ance because lif e span is not aff ect ed. This slow ly progressive low er
mot or neuronopat hy of men in t he t hird t o f if t h decades is charact erized by
proximal low er mot or neuron w eakness associat ed w it h f acial and t ongue
w eakness and f asciculat ions, gynecomast ia, t est icular at rophy, hypogonadism,
inf ert ilit y, and diabet es[72] . A post ural t remor of t he hands may be seen as w ell.
Vascular Syndromes of the Spinal Cord

Spinal cord inf arct ion is a very rare occurrence w hen compared w it h cerebral
inf arct ion. Most spinal cord inf arct s result f rom t he involvement of t he t errit ory of
t he ant erior spinal art ery, w hich supplies t he ant erior f uniculi, ant erior horns,
base of t he dorsal horns, periependymal area, and ant eromedial aspect s of t he
lat eral f uniculi [27, 77, 78, 100] . The low er t horacic segment of t he spinal cord
and conus medullaris are most f requent ly involved. Pat ient s w it h t he ant erior
spinal art ery syndrome have an abrupt onset , and is of t en associat ed w it h
radicular or “girdle” pain. Loss of mot or f unct ion (e. g. , f laccid t et raplegia or
paraplegia) occurs w it hin minut es on hours below t he level of t he lesion (bilat eral
cort icospinal t ract damage). There is impaired bow el and bladder cont rol, and
t hermoanest hesia and analgesia below t he level of t he lesion (compromise of t he
spinot halamic t ract s bilat erally). Posit ion sense, vibrat ion, and light t ouch remain
int act because of t he preservat ion of t he dorsal columns (supplied by t he
post erior spinal art eries). Pat ient s may develop painf ul burning dysest hesias
below t he level of cord injury, likely relat ed in part t o select ive neospinot halamic
deaff erent at ion and preservat ion of t he post erior columns[95] . Concomit ant
inf arct s t o one or more vert ebral bodies can be seen[101] . Spinal cord inf arct ion
of t en occurs in “w at ersheds” or boundary zones w here t he major art erial
syst ems supplying t he spinal cord anast omose at t heir most dist al branches.
These boundary zones include t he T1 t o T4 and t he L1 segment s. Cells of t he
peripheral gray mat t er are more resist ant t o ischemia/ anoxia t han t hose cent rally
locat ed. O n an axial sect ion, t he w at ershed zone of t he spinal cord involves t he
paracent ral w hit e mat t er of t he lat eral and ant erior f uniculi. According t o Zulch,
w at ershed inf arct ion of t he spinal cord is most likely t o develop at t he T4
segment along t he boundary zone of supply bet w een t he ant erior and post erior
spinal art eries[102] . How ever, t his t radit ional not ion of increased ischemic
vulnerabilit y of t he t horacic spinal cord w at ershed zone near T4 has been
challenged[ 17] .
I nit ially described w it h syphilit ic art erit is, spinal cord inf arct ion may result f rom
aort ic dissect ion, at herosclerosis of t he aort a and it s branches, acut e aort ic
t hrombosis, f ollow ing surgery of t he abdominal aort a or repair of coarct at ion of
t he aort a, cervical spondylosis[41] , f ract ure/ dislocat ion of t he spine or t raumat ic
neck injury[39] , f ibrocart ilaginous embolism[60] , af t er rib resect ion f or
sympat hect omy[ 43] , af t er t horacoplast y and t horacot omy[75] , af t er spinal
art eriovenous malf ormat ion t hrombosis or repair[17] f ollow ing severe art erial
hypot ension or cardiac arrest [48] , celiac plexus block[17] , w it h decompression
sickness [17] , w it h syst emic lupus eryt hemat osus, and w it h vasculit is [17, 29,
40] . Spinal cord inf arct ion in AI DS may result f rom acut e or chronic vasculit is or
disseminat ed int ravascular coagulat ion. I n a subst ant ial number of cases, no
cause can be f ound.
I nf arct ion in t he t errit orial supply of t he post erior spinal art eries is uncommon.
I t s manif est at ions include loss of propriocept ion and vibrat ion sense below t he
level of t he lesion and loss of segment al ref lexes[42] . I nf arct ion of t he unilat eral
post erior horn and lat eral column of t he spinal cord w it h sparing of t he post erior
columns may also rarely occur w it h post erior spinal art ery occlusion[47] . I n
inst ances of hypoxic myelopat hy, t he onset of sympt om is more gradual; w it h t he
ent it y of spinal cord claudicat ions, sympt oms are precipit at ed by exert ion. The
salient f eat ures of t he major clinical syndromes of spinal cord inf arct ion are
summarized in Table 5-1.
Venous spinal cord inf arct ion may also occur, w it h most occurring as a result of
impaired blood drainage in pat ient s w it h dural art eriovenous f ist ulas (AVFs) or
w it h hypercoagulable st at es t hat cause i nsi tu t hrombosis. Since t he spinal veins
lack valves and drain int o t he azygos and pelvic venous syst em, t here is a
pot ent ial f or ret rograde embolizat ion of t hrombi associat ed w it h inf ect ious
abdominal processes, of f ibrocart ilaginous emboli f rom adjacent discs, and
rarely of f oreign mat erials (e. g. , w it h sclerot herapy f or esophageal varices[83] ).
Dural AVFs t ypically occur in t he low er t horacic or upper lumbar region. The
underlying pat hophysiology is relat ed t o venous hypert ension. I f lef t unt reat ed,
chronic venous hypert ension may lead t o irreversible spinal cord injury. Most
commonly in middle-aged men, t he clinical pict ure is charact erized by a slow ly
progressive myelopat hy. Venous t hrombosis may cause abrupt clinical
det eriorat ion. [ 20] . Vascular malf ormat ions of t he spinal cord include
art eriovenous malf ormat ions (AVMs), AVFs, dural AVFs, epidural vascular
malf ormat ions, cavernous malf ormat ions, and complex vascular malf ormat ions
(Cobb's syndrome, and O sler-Weber-Rendu syndrome). The syndrome of
subacute necroti zi ng myel opathy described by Foix and Alajouanine is
charact erized by an of t en asymmet rical paraparesis, accompanied by varying
degrees of pain and sensory dist urbances in t he ext remit ies, bladder, bow el, and
sexual dysf unct ion, evolving in a slow ly progressive f ashion result ing f rom an
angiodysgenet ic necrot izing myelopat hy w it h impaired venous out f low [25, 61] .
I mpaired epidural spinal cord venous drainage has also been implicat ed as a
major pat hogenet ic mechanism in decompression sickness (Caisson disease), in
w hich myelopat hic sympt oms, t hought t o be due t o t he release of nit rogen
bubbles w it hin t he spinal canal, predominat e[34] .
TABLE 5-1 Clinical M anifestations of Spinal Cord

Ischemia
Anterior Spinal Artery Syndrome

Back of neck pain of sudden onset
Rapidly progressive flaccid and areflexic paraplegia
Loss of pain and temperature to a sensory level
Preservation of proprioception and vibration sensation
Urinary incontinence
Posterior spinal artery syndrome
Loss of proprioception and vibratory sense
Preserved pain and temperature sensation except for
involved segment of cord, where global anesthesia is
present
Loss of myotatic and cutaneous reflexes below involved
segment
Absence of motor deficits
Isolated Focal Motor or Sensory Deficits in Extremities,
Which May Represent Lacunar Infarctions
Slowly Progressive Paraparesis or Quadriparesis
(Hypoxic Myelopathy)
Spinal Cord Claudication (Hemodynamic Transient
Ischemic Attacks or TIAs)
The diff erent ial diagnosis of spinal cord inf arct ion includes any condit ion capable
of rapidly producing a part ial t ransverse spinal cord lesion, such as spinal cord
compression, spinal cord t rauma, acut e parainf ect ious or demyelinat ing myelit is,
and cent ral spinal cord syndromes caused by t umors or hemorrhages. The
salient causes of art erial and venous spinal cord inf arct ions are summarized in
Tables 5-2 and 5-3.
Extramedullary Cord Lesions and Their Differentiation

from Intramedullary Cord Lesions
I t is import ant t o det ermine w het her a lesion lies out side t he cord
(ext ramedullary) or w it hin t he cord (int ramedullary) and w het her an
ext ramedullary lesion is int radural or ext radural. Alt hough t he clinical dist inct ion
bet w een int ramedullary and ext ramedullary lesions is never absolut e, cert ain
clinical guidelines are of t en helpf ul (Table 5-4)[ 30, 71] .
Pain
O ppenheim[ 65] dist inguished t hree clinical st ages of spinal cord compression:
(a) radicular pain and segment al mot or and sensory disrupt ion,
(b) incomplet e t ransect ion (i. e. , Brow n-Séquard syndrome), and (c) complet e
cord t ransect ion. As in t he degenerat ive joint disease of t he spine, t he pain f rom
met ast at ic epidural spinal cord compression is exacerbat ed by movement , t he
Valsalva's maneuver, st raight leg raising, and neck f lexion. Unlike t he pain f rom
degenerat ive joint disease, t he pain f rom met ast at ic epidural spinal cord
compression is f requent ly exacerbat ed by recumbence [14] .
TABLE 5-2 Causes of Arterial Spinal Cord Infarction
Atherosclerosis
Severe arterial hypotension or cardiac arrest
Aortic surgery
Traumatic laceration of the aorta
Dissecting aortic aneurysm
Thrombo-occlusive aortic disease
Infection (lues, tuberculosis)
Vasculitis
Carcinomatous meningitis
Neoplastic spread to the spinal cord
Hypertensive small vessel disease
Subarachnoid hemorrhage
Sickle cell anemia
Systemic lupus erythematosus
Antiphospholipid antibody syndrome
Disseminated intravascular coagulation
Cervical spondylosis
Spine fracture or dislocation
Vertebral artery occlusion or dissection
Rib resection for sympathectomy
Lumbar sympathectomy
Thoracoplasty for tuberculosis
Thoracotomy
Intercostal artery ligation
Celiac plexus block
Decompression sickness (Caisson disease)
Atheromatous emboli
Cholesterol emboli
Fibrocartilaginous emboli
Atrial myxoma
Aortic or spinal cord angiography
Intra-aortic balloon pump
Lumbar artery compression
Adapted from Cheshire W P, Santos CS, Massey EW, et

al. Spinal cord infarction. Etiology and outcome.
Neurology 1996;47:321–330; and W illiams LS, Bruno A,
Biller J. Spinal cord infarction. Top Stroke Rehabil
1996;3:41–53.
Pain is an import ant early sign of cord compression and may be classif ied as
one of t hree t ypes: root (radicular) pain, vert ebral pain, and f unicular (cent ral)
pain.
1. Radi cul ar pai n is charact erized as a unilat eral, lancinat ing, dermat omal pain
of t en exacerbat ed by cough, sneeze, or Valsalva's maneuver. Radicular pain
is common w it h ext radural grow t hs and rare w it h int ramedullary lesions. An
example of an ext ramedullary t umor causing radicular pain is t he
neurilemmoma (usually an int radural-ext ramedullary lesion). Wit h
neurilemmomas, root pain predominat es and may be t he exclusive sympt om
bef ore dermat omal hypest hesia and segment al paresis, amyot rophy, and
f asciculat ions develop.
2. Vertebral pai n is charact erized by an aching pain localized t o t he point of t he
spine involved in t he compressive process and of t en accompanied by point
t enderness. Spinal pain is common w it h neoplast ic or inf lammat ory ext radural
lesions and inf requent w it h int ramedullary or int radural-ext ramedullary
lesions.
3. Funi cul ar (central ) pai n is common w it h int ramedullary lesions and very
unusual w it h ext radural lesions. I t is described as deep, ill-def ined painf ul
dysest hesias, usually dist ant f rom t he aff ect ed spinal cord level (and
t heref ore of poor localizing value), probably relat ed t o dysf unct ion of t he
spinot halamic t ract or post erior columns.
TABLE 5-3 Causes of Venous Spinal Cord Infarction
Thrombophlebitis
Chronic meningitis
Decompression sickness (Caisson disease)
Acute myelogenous leukemia
Spinal cord glioma
Polycythemia rubra vera
Esophageal vein sclerotherapy
Liver abscess (embolization of venous material)
Fibrocartilaginous emboli
Adapted from W illiams LS, Bruno A, Biller J. Spinal

cord infarction. Top Stroke Rehabil 1996;3:41–53.
TABLE 5-4 Clinical Guidelines to Differentiate

Intramedullary and Extramedullary Tumors
Intram edullary Extram edullary

Sym ptom s/Signs
Tum ors Tum ors
Common, may
Radicular pain Unusual
occur early
Vertebral pain Unusual Common
Funicular pain Common Less common
Upper motor
Yes, late Yes, early
neuron signs
Unusual, if
Lower motor Prominent and present,
neuron signs diffuse segmental
distribution
Paresthesia's Descending
Ascending
progression progression
Early with caudal

Sphincter lesions
Late
abnormalities (conuscauda
equina)
Trophic changes Common Unusual
Disturbances of M otor Function

Mot or dysf unct ion may be secondary t o t he compromise of t he low er mot or
neuron, upper mot or neuron, or bot h. Lesions compressing t he cort icospinal t ract
gradually and chronically result in spast icit y, w hereas acut e lesions result in
f laccid paresis.
Upper mot or neuron signs t end t o occur lat e w it h int ramedullary lesions and
early w it h ext ramedullary cord lesions. The coexist ence of upper and low er
mot or neuron signs is suggest ive of an int ramedullary lesion but does not
exclude an int radural-ext ramedullary process.
Parest hesias may f ollow a radicular or f unicular dist ribut ion. Some pat ient s may
develop a “pins-and-needles” sensat ion dist ally, resembling a polyneuropat hy,
w hereas ot hers develop sensory sympt oms t hat have an “ascending” pat t ern.
Subject ive sensory complaint s may or may not be associat ed w it h object ive
sensory loss. For example, in cases of monoradicular involvement , pat ient s may
have subject ive sensory dermat omal complaint s but , because of dermat omal
overlap, t hey lack object ive sensory changes. A descending progression of
parest hesias is more common w it h int ramedullary lesions, w hereas ascending
progression of parest hesias suggest s an ext ramedullary lesion.
A sensory l evel of pain and t emperat ure must be sought in all cases of
suspect ed spinal cord disease. A sensory level is, how ever, not very helpf ul in
dist inguishing int ramedullary f rom ext ramedullary lesions. A Brow n-Séquard
syndrome is more common w it h ext ramedullary lesions but cert ainly not unusual
w it h int ramedullary lesions.
Dissociat ed sensory loss and sacral sparing (ow ing t o t he somat ot opic
organizat ion of t he spinot halamic t ract ) are charact erist ic of int ramedullary cord
involvement . Wit h int ramedullary lesions, vibrat ory sensat ion is usually more
impaired t han posit ion sense.
Disturbances of Sphincter Function

Urinary and f ecal incont inence or ret ent ion may be t he most unaccept able
sympt oms f or many pat ient s, causing t hem t o seek medical at t ent ion. Early loss
of sphinct er cont rol w it h associat ed saddle anest hesia is common w it h t umors
arising in t he conus medullaris (int ramedullary) and w it h t umors aff ect ing t he
cauda equina (ext ramedullary). Lesions at higher spinal levels (int ramedullary or
ext ramedullary) t end t o be associat ed w it h dist urbances of sphinct er f unct ion
only w it h ext ensive bilat eral cord damage.
Autonomic M anifestations
O cular sympat het ic palsy (Horner syndrome) may be associat ed w it h eit her
ext ramedullary or int ramedullary t umors. Vasomot or and sudomot or abnormalit ies
are of no clinical value in dist inguishing int ramedullary f rom ext ramedullary
lesions. Sexual dysf unct ion is inf requent .
Localization of Spinal Cord Lesions at Different Levels

Foramen Magnum Syndrome and Lesions of the Upper
Cervical Cord
Neurologic f indings w it h lesions of t he f oramen magnum consist of a complex
array of sensory,
mot or, and neuro-opht halmologic f indings[92] . Suboccipit al pain in t he

dist ribut ion of t he great er occipit al nerve (C2) and neck st iff ness occur early.
Elect ric shock–like sensat ions radiat ing dow n t he spine, w hich may be
t ransmit t ed t o t he ext remit ies, may occur w it h neck f lexion (Lhermit t e's
sympt om) and indicat e a lesion of t he post erior columns (most of t en mult iple
sclerosis or cervical spondylosis)[ 31] . Subject ive occipit al parest hesias and,
rarely, sensory f indings indicat ive of post erior column dysf unct ion or a
“syringomyelic” t ype of sensory dissociat ion may be present . Numbness and
t ingling of t he f ingert ips are common. I n addit ion t o high cervical cord
compressive f indings (spast ic t et raparesis, long t ract sensory f indings, bladder
dist urbance), low er cranial nerve palsies (cranial nerves I X–XI I ) may occur by
regional ext ension of t he pat hologic process. An “around t he clock” present at ion
of upper mot or neuron dist ribut ion w eakness t ypically involves t he ipsilat eral
upper ext remit y, spreading t o involve t he ipsilat eral low er ext remit y, bef ore
involving t he cont ralat eral low er ext remit y and t hen t he upper ext remit y. This
present at ion event ually result s in hemiparesis, t riparesis, or quadriparesis.
Lesions at t he f oramen magnum may be associat ed w it h dow nbeat nyst agmus,
papilledema (secondary t o cerebrospinal f luid circulat ion obst ruct ion), and
cerebellar at axia. The major diagnost ic considerat ions include t umors (e. g. ,
meningiomas, neurof ibromas, gliomas, t erat omas, met ast ases), cervical
spondylosis, basilar invaginat ion in Paget 's disease, syrinx, Chiari malf ormat ion,
at lant oaxial subluxat ion (e. g. , rheumat oid art hrit is), and mult iple sclerosis.
Where t he pyramidal t ract decussat es at t he medullocervical junct ion w it h
segregat ion of arm f ibers (rost ral) and leg f ibers (caudal), a lesion can cause
t he unusual combinat ion of cont ralat eral upper ext remit y paresis and ipsilat eral
low er ext remit y paresis (hemi pl egi a cruci ata). The t erm cruci ate paral ysi s has
also been used t o indicat e arm w eakness in excess of leg w eakness in pat ient s
w it h cervicomedullary junct ion injuries or malf ormat ions[21] . Pat ient s w it h t his
condit ion may also demonst rat e an onionskin pat t ern of f acial sensory loss,
respirat ory insuff iciency, bladder dysf unct ion, and impairment of ot her cranial
nerves[ 21] .
Compressive lesions of t he upper cervical cord (C1–C4 segment s)[ 63] may
compromise cranial nerve XI (C1–C5 cord segment s), w hich innervat es t he
st ernocleidomast oid muscle and t he upper port ion of t he t rapezius muscle. I n
addit ion t o sensory loss in t he dist ribut ion of t he aff ect ed level, t here is an
anomalous head posit ion, inadequat e cont ract ion and at rophy of t he
st ernocleidomast oid muscle, and inabilit y t o elevat e t he shoulder t ow ard t he
ipsilat eral ear. Diaphragmat ic paralysis may be seen w it h lesions involving t he
C3–C5 cord segment s, causing limit ed lat eral expansion of t he low er rib cage
during inspirat ion. The involvement of t he descending respirat ory pat hw ays at
high cervical spinal cord levels can also be associat ed w it h respirat ory
insuff iciency and respirat ory arrest [37] .
False localizing sensory and mot or f indings, including t horacic sensory levels,
propriocept ive sensory loss, parest hesias of t he hands, and clumsiness and
at rophy of t he hands, can occur w it h disorders aff lict ing t he upper and
midcervical cord. For example, midline disc prot rusion at t he C3–C4 level may be
associat ed w it h numbness of t he f ingert ips and palms, clumsiness of t he hands,
and a t ight ening sensat ion at t he midt horacic level[62] and ext radural lesions
above C4 may cause f inger and hand dysest hesias and hand at rophy[88] . An
aw areness of t hese “f alse localizing” signs is crucial t o t he physician's abilit y t o
correct ly ident if y such lesions [62, 85, 88] .
Lesions of the Fifth and Sixth Cervical Segments

Compression of t he low er cervical spinal cord causes low er mot or neuron signs
at t he corresponding segment al levels and upper mot or neuron signs below t he
lesion (e. g. , spast ic paraplegia). Lesions aff ect ing t he C5 and C6 segment s
cause low er mot or neuron signs t hat aff ect especially t he spinat i, delt oid,
biceps, brachioradialis, brachialis, pect orals, lat issimus dorsi, t riceps, and
ext ensor carpi radialis muscles, among ot hers. This low er mot or neuron paresis
of t he arm is associat ed w it h spast ic paraparesis of t he low er ext remit ies.
Diaphragmat ic f unct ion may be compromised (C5 aff ect ion). Wit h C5 segment
lesions, t he biceps (segment s C5–C6) and t he brachioradialis (segment s C5–C6)
ref lexes are absent or diminished, w hereas t he t riceps ref lex (segment s C6–C8)
and t he f inger f lexor ref lex (segment s C8–T1) are exaggerat ed (t he lat t er t w o
are exaggerat ed ow ing t o cort icospinal t ract compression at t he C5 level).
Theref ore, C5 segment al lesions result in an i nversi on of the brachi oradi al i s
ref l ex. Tapping of t he radius elicit s exaggerat ed f inger and hand f lexions w it hout
f lexion and supinat ion of t he f orearm. Wit h C6 segment al lesions, t he biceps
(segment s C5–C6), brachioradialis (segment s C5–C6), and t riceps (segment s
C7–C8) ref lexes are depressed or absent , but t he f inger f lexor ref lex (segment s
C8–T1) is exaggerat ed.
Wit h complet e C5 segment lesions, sensory loss occurs over t he ent ire body
below t he neck and ant erior shoulder; w it h C6 sensory lesions, t he same sensory
loss occurs, except t hat t he lat eral arm is spared.
Lesions of the Seventh Cervical Segment

Wit h lesions of t he C7 segment , diaphragmat ic f unct ion is normal. Paresis
involves t he f lexors and t he ext ensors of t he w rist s and f ingers. The biceps and
brachioradialis ref lexes (segment s C5–C6) are preserved, w hereas t he f inger
f lexor ref lex (segment s C8–T1) is exaggerat ed. There may be a paradoxi cal
tri ceps ref l ex consist ing of f lexion of t he f orearm f ollow ing t apping of t he
olecranon (w eakness of t he t riceps prevent s t riceps cont ract ion and elbow
ext ension, w hile muscles innervat ed by normal segment s above t he lesion are
allow ed t o cont ract ). Wit h C7 segment lesions, t here is sensory loss at and
below t he t hird and f ourt h digit s (including t he medial arm and f orearm).
Lesions of the Eighth Cervical and First Thoracic

Segments
Lesions at t he C8 and T1 segment s level result in w eakness t hat predominant ly
involves t he small hand muscles. There is associat ed spast ic paraparesis. Wit h
C8 lesions, t he t riceps ref lex (segment s C7–C8) and t he f inger f lexor ref lex
(segment s C8–Tl) are decreased or absent ; w it h T1 lesions, t he t riceps ref lex
(segment s C7–C8) is preserved, but t he f inger f lexor ref lex (segment s C8–Tl) is
decreased. Wit h C8–T1 lesions, t here may be a unilat eral or bilat eral Horner
syndrome. Sensory loss involves t he f if t h digit and t he medial f orearm and arm
as w ell as t he rest of t he body below t he lesion.
FI G URE 5-4 Wat ershed region of blood supply t o t he cervical cord. Tract
laminat ion: C = cervi cal; T = thoraci c; L = l umbar; S = sacral
Rarely, spondylot ic narrow ing of t he spinal canal at t he C3–C4 and C5–C6 levels
may cause hand muscle (C8–T1) w ast ing w it h sparing of t he C5 and C6
myot omes[ 89] . Presumably, t his w ast ing is due t o t he ant erior horn cell damage
caused by st agnant hypoxia secondary t o venous congest ion of t he low cervical
cord induced by t he midcervical lesion.
Spondylot ic cervical myelopat hy may present w it h a clinical pict ure dominat ed by
a glove dist ribut ion sensory loss in t he hands also know n as t he syndrome of
numb, cl umsy hands [ 97, 76] . The hand sensory loss is of t en global, and in
some pat ient s t he involvement ext ends proximally as f ar as t he elbow s. Mot or
f indings in t he hands may be no more t han mild t o moderat e, as may be t he
mot or and sensory f indings in t he legs. Most pat ient s have compressive lesions,
and t he syndrome is t hought t o result f rom ischemia of t he int rinsic border areas
of collat eralizat ion bet w een t he superf icial pial net w ork and t he cent ral art erial
supply t o t he cervical cord (Fig. 5-4), alt hough venous st agnat ion may also play
a role[97] . Anot her syndrome suggest ive of cervical spondylot ic myelopat hy
includes t he sudden onset of quadriplegia or paraplegia af t er a minor f all in an
elderly pat ient [70] .
Lesions of the Thoracic Segments

Lesions of t he t horacic segment s are charact erized by root pain or parest hesias
t hat mimic int ercost al
neuralgia. Segment al low er mot or neuron involvement is diff icult t o det ect
clinically. Paraplegia, sensory loss below a t horacic level, and dist urbances of
bladder, bow el, and sexual f unct ion occur. O ccasionally, t here is a quard
syndrome Brow n-Séquard, a cent ral cord, or an ant erior cord syndrome. Wit h
lesions above T5, t here may be impairment of vasomot or cont rol, result ing in
syncope on arising (because of ort host at ic blood pressure changes). Epi sodi c
autonomi c dysref l exi a may also occur w it h lesions rost ral t o t he T5 level in
w hich a st imulus (usually dist ent ion of t he bladder or rect um) result s in excessive
sw eat ing (especially rost ral t o t he sensory level of t he lesion), cut aneous
f lushing, hypert ension, pounding headache, and ref lex bradycardia.
Wit h a cord lesion at t he T10 level, t he upper abdominal muscular f unct ion is
preserved, w hereas t he low er abdominal muscles are w eak; t heref ore, w hen t he
head is f lexed against resist ance (pat ient supine), t he int act upper abdominal
muscles pull t he umbilicus upw ard (Beevor's si gn).
I f a lesion lies above T6, no superf icial abdominal ref lexes can be elicit ed. I f it is
at or below T10, t he upper and middle abdominal ref lexes are present ; if it is
below T12, all abdominal ref lexes are present .
Lesions of the First Lumbar Segment

Wit h L1 segment al cord lesions, all muscles of t he low er ext remit ies are w eak.
Low er abdominal paresis (int ernal oblique, t ransversus, and abdominis muscles)
may occur, but t his is diff icult t o demonst rat e. The area of sensory loss includes
bot h t he low er ext remit ies up t o t he level of t he groin and t he back, t o a level
above t he but t ocks. Wit h chronic lesions, t he pat ellar (segment s L2–L4) and
ankle jerks (segment s S1–S2) are pat hologically brisk.
Lesions of the Second Lumbar Segment

There is spast ic paraparesis but no w eakness of t he abdominal muscles. The
cremast eric ref lex (segment L2) is not elicit able and t he pat ellar jerks (segment s
L2–L4) may be depressed. The ankle jerks (segment s S1–S2) are hyperact ive.
There is normal sensat ion on t he upper ant erior aspect of t he t highs.
Lesions of the Third Lumbar Segment

There is some preservat ion of t he hip f lexion (iliopsoas and sart orius) and leg
adduct ion (adduct or longus, pect ineus, and gracilis). The pat ellar jerks
(segment s L2–L4) are decreased or not elicit able; t he ankle jerks are
hyperact ive. There is normal sensat ion on t he upper ant erior aspect of t he
t highs.
Lesions of the Fourth Lumbar Segment

There is bet t er hip f lexion and leg adduct ion t han t hat f ound in L1–L3 lesions.
Knee f lexion and leg ext ension are bet t er perf ormed, and t he pat ient is able t o
st and by st abilizing t he knees. The pat ellar jerks (segment s L2–L4) are not
elicit able; t he ankle jerks (segment s S1–S2) are hyperact ive. Sensat ion is
normal on t he ant erior aspect of t he t highs and superomedial aspect s of t he
knees.
Lesions of the Fifth Lumbar Segment

There is normal hip f lexion and adduct ion and leg ext ension. O w ing t o t he normal
st rengt h of t he quadriceps f emoris muscles, t he pat ient is able t o ext end t he
legs against resist ance w hen t he ext remit ies are f lexed at t he hip and knee. The
pat ellar ref lexes (segment s L2–L4) are present ; t he ankle jerks (segment s S1–
S2) are hyperact ive. Sensory f unct ion is preserved on t he ant erior aspect of t he
t highs and t he medial aspect s of t he legs, ankles, and soles.
Lesions of the First and Second Sacral Segments

Wit h lesions of t he S1 segment , t here is w eakness of t he t riceps surae, f lexor
digit orum longus, f lexor hallucis longus, and small f oot muscles. The Achilles
ref lexes (segment s S1–S2) are absent , w hereas t he pat ellar ref lexes (segment s
L2–L4) are preserved. There is complet e sensory loss over t he sole, heel, and
out er aspect of t he f oot and ankle. The medial aspect s of t he calf and post erior
t high and t he out er aspect of t he “saddle” area are also anest het ic.
The gast rocnemius and soleus muscles are st ronger w it h S2 segment al lesions;
how ever, t he f lexor digit orum, f lexor hallucis longus, and small muscles of t he
f oot remain w eak, and t he Achilles ref lexes (segment s S1–S2) may be
hypoact ive. The sensory loss t ends t o involve t he upper part of t he dorsal aspect
of t he calf , t he dorsal lat eral aspect of t he t high, and t he saddle area.
Conus Medullaris Lesions

Lesions of t he conus medullaris[3] cause paralysis of t he pelvic f loor muscles
and early sphinct er
dysf unct ion. Disrupt ion of t he bladder ref lex arc result s in an aut onomous
neurogenic bladder charact erized by loss of volunt ary init iat ion of mict urit ion,
increased residual urine, and absent vesical sensat ion. Const ipat ion and
impaired erect ion and ejaculat ion are commonly present . Pat ient s may have a
symmet ric saddle anest hesia. Pain is not common but may occur lat e in t he
clinical course and involves t he t highs, but t ocks, and perineum.
A t et hered spinal cord (i. e. , t he t et hered cord or t he low conus syndrome) may
present w it h a combinat ion of various neurologic, urologic, ort hopaedic, and
dermat ologic manif est at ions. Many of t hese condit ions are seen in associat ion
w it h spina bif ida occult a or prior reconst ruct ive surgery of a myelomeningocele
or lipomeningocele. Commonly, pat ient s present w it h numbness of t he f eet ,
asymmet ric muscle at rophy of t he calf or t high muscles, upper mot or neuron
signs, bow el and bladder dysf unct ion, f oot def ormit ies, pes cavus, equinovarus,
t alipes, scoliosis, and cut aneous manif est at ions of spinal dysraphism (e. g. ,
lumbosacral midline hair t uf t , midline nevus, dermal sinus t ract s, hypert richosis,
and subcut aneous sacral lipomat ous masses)[ 24, 81] .
Cauda Equina Lesions

O w ing t o t he compression of t he lumbar and sacral root s below t he L3 vert ebral
level, cauda equina lesions cause early radicular pain in t he dist ribut ion of t he
lumbosacral root s[5] . Pain may be unilat eral or asymmet ric and is increased by
t he Valsalva's maneuver. Wit h t umors of t his region (e. g. , ependymoma,
schw annoma, meningioma), pain is of t en w orse at night or w hen t he pat ient
assumes a recumbent posit ion. Wit h ext ensive lesions, pat ient s develop f laccid,
hypot onic, aref lexic paralysis t hat aff ect s t he glut ei, post erior t high muscles, and
ant erolat eral muscles of t he leg and f oot , result ing in a t rue peripheral t ype of
paraplegia. Sensory t est ing usually reveals an asymmet ric sensory loss in t he
saddle region, involving t he anal, perineal, and genit al regions ext ending t o t he
dorsal aspect of t he t high, t he ant erolat eral aspect of t he leg, and t he out er
aspect of t he f oot .
The Achilles ref lexes (segment s S1–S2) are absent and t he pat ellar ref lexes
(segment s L2–L4) are variable in t heir response. Sphinct er changes are similar
t o t hose not ed w it h conus medullaris lesions but t end t o occur lat e in t he clinical
course. Lumbar disc herniat ion may cause a cauda equina syndrome w hen t he
herniat ion is associat ed w it h a narrow spinal canal and a low -lying conus
medullaris[ 84] .
Alt hough it can be concluded t hat lesions of t he conus medullaris result in early
sphinct er compromise, lat e pain, and symmet rical sensory manif est at ions,
w hereas cauda equina lesions have lat e sphinct er manif est at ions, early pain, and
asymmet rical sensory f indings, t his dist inct ion is of t en exceedingly diff icult t o
est ablish and is of lit t le pract ical value. An overview of t he main causes of
myelopat hies is included in Table 5-5.
Neurogenic Bladder with Spinal Cord Lesions

The classif icat ion of t he neurogenic bladder is complex and requires adequat e
f unct ional neuroanat omic and urodynamic know ledge [11, 12, 22, 26, 77] . The
st orage and evacuat ion of urine ult imat ely depend on a spinal ref lex arc.
How ever, supraspinal input is needed t o preserve cont inence and t o post pone
bladder empt ying in appropriat e circumst ances. The aff erent arc of t he spinal
ref lex arises f rom t he dist ent ion of t he bladder st ret ch recept ors, locat ed in t he
bladder w all, and t ravels t hrough t he parasympat het ic nerves t o t he cent er f or
mict urit ion (det rusor cent er or sacral parasympat het ic nucleus) locat ed in sacral
segment s S2–S4 of t he spinal cord. The eff erent (parasympat het ic) arc t ravels
t hrough t he pelvic nerves t o t he pelvic plexus; short post ganglionic f ibers t ravel
f rom t he plexus t o t he det rusor muscle. Most aff erent f ibers (conveying t he
sensat ion of bladder f ullness) do not end in t he sacral levels of t he spinal cord
but ascend t o synapse on relay cells locat ed in t he dorsal pontomesencephal i c
reti cul ar f ormati on mi cturi ti on center (locat ed in t he locus ceruleus,
pont omesencephalic gray mat t er, and nucleus t egment olat eralis dorsalis). O t her
aff erent f ibers t ravel f urt her rost rally t o t he cort ical and subcort ical mict urit ion
cent ers. The cerebral cont rol of mict urit ion is locat ed in t he superomedial port ion
of t he f ront al lobe, t he ant erior aspect of t he cingulat e gyrus, and t he genu of
t he corpus callosum. Cont ribut ions f rom subcort ical cent ers arise f rom t he
t halamic nuclei, t he limbic syst em, t he red nucleus, t he subst ant ia nigra, t he
hypot halamus, and t he subt halamic nucleus. I n addit ion, t he ant erior vermis of
t he cerebellum and f ast igial nucleus are concerned w it h mict urit ion. Posit ron
emission t omography (PET) st udies among volunt eers have show n a
lat eralizat ion of t he specif ic areas responsible f or t he cont rol of mict urit ion, w it h
preliminary evidence t hat cort ical and pont ine mict urit ion sit es are more act ive
on t he right t han on t he lef t side. Furt hermore, mict urit ion w as associat ed w it h
an increased blood f low in t he right dorsomedial pont ine t egment um,
t he periaqueduct al gray, t he hypot halamus, and t he right inf erior f ront al gyrus,
w hereas decreased blood f low w as not ed in t he right ant erior cingulat e gyrus
w hen urine w as w it hheld[9, 10] .
TABLE 5-5 M yelopathies
Congenital
Diastematomyelia (spinal notochord syndrome)
Traumatic
Nonpenetrating injuries
Penetrating injuries
Spondylogenic
Craniocervical junction abnormalities
Atlantoaxial anomalies (Down's syndrome)
Cervical spondylotic myelopathy
Cervical disc herniation with spinal cord compression
Thoracic disc herniation with thoracic spinal stenosis
Diffuse idiopathic skeletal hyperostosis (Forestier's
disease)
Ossification of the posterior longitudinal ligament
Rheumatoid disease of the spine (RA)
Anterior atlantoaxial subluxation
Posterior atlantoaxial subluxation
Vertical atlantoaxial subluxation
Cervical/Thoracic spine pachymeningitis
Thoracic cord compression by rheumatoid nodules
Thoracic spinal cord infarction due to vasculitis
Syringomyelia due to cervical cord compression
Transverse myelopathy associated with
antiphospholipid antibodies
Transverse myelitis due to sulfadiazine
Myelopathy in SLE
SLE myelopathy
Transverse myelopathy associated with
antiphospholipid antibodies
Herpes zoster myelitis
Compression fracture (long-term corticosteroid use)
with spinal cord compression
Spinal epidural/subdural hemorrhages
Epidural lipomatosis
Tuberculous spondylitis
Atlantoaxial subluxation
Spondyloarthropathies
Ankylosing spondylitis
Reiter's syndrome
Reactive arthritis
Psoriatic arthritis
Associated with inflammatory bowel disease
Undifferentiated spondyloarthropathies
W hipple's disease
Behcet's disease
Demyelinating
Multiple sclerosis
Devic's neuromyelitis optica
Acute disseminated encephalomyelitis
Postinfectious and postvaccinal myelopathies
Inflammatory transverse myelitis
Osmotic demyelination syndrome
Leukodystrophies
Infectious
Bacterial (tuberculosis, pyogenic infections)
Viral (e.g., HIV, HTLV-1)
Parasitic (e.g., schistosomiasis, hydatid disease)
Other (e.g., syphilis, Lyme disease, Mycoplasma)
Granulomatous disorders
Sarcoidosis
W egener's granulomatosis
Vascular
Vasculitis
Spinal artery (anterior, posterior) occlusion
Venous spinal cord infarction
Vascular malformations
Metabolic
B 12 deficiency
Copper deficiency
Hyperthyroidism
Diabetes mellitus
Mitochondrial disorders
Spinal tumors
Tumors of bone (primary–secondary)
Plasma cell dyscrasias multiple myeloma, solitary
plasmacytoma
Extradural (metastatic carcinoma, lymphomas,
malignant melanoma)
Intradural extramedullary
Intramedullary (astrocytomas, glioblastoma multiforme,
ependymoma, primitive neuroectodermal tumors,
gangliocytoma, neurocytoma, lipoma, epidermoid cyst,
meningioma)
Nontumoral myelopathies
Subacute necrotizing myelopathy of Foix and
Alajouanine
Subacute paraneoplastic necrotizing myelopathy (lung
carcinoma, lymphomas)
Drugs and Toxic Myelopathies
Neurolathyrism (latirus sativus–β–oxalyl–amino–L-
alanine)
Konzo (cyanogenic glucosides from bitter casava)
Subacute myelo-optic neuropathy
Methotrexate, cytosine
Intravenous heroin
Systemic disorders
Portocaval encephalomyelopathy
Inflammatory bowel disease
Celiac disease
Physical agents
Electrical or lightning injuries
Radiation
Caisson disease (decompression sickness)
System Degeneration
Hereditary spastic paraplegia
Spinal muscular atrophies
Amyotropic lateral sclerosis (sporadic/familial)
Inherited disorders
Syringomyelia
Chiari malformations
Miscellaneous
Myelopathy with corpora amylacea–Polyglucosan body
disease
Spinal cord herniation
RA = rheumatoid arthritis; SLE = systemic lupus

erythematosus; HIV = human immunodeficiency virus;
HTLV-1 = human T-lymphotropic virus type 1.
From t he pont omesencephalic mict urit ion cent er, eff erent s t o t he spinal cord
descend by w ay of t he ret iculospinal t ract s (locat ed medially and ant eriorly in
t he ant erior f uniculus) t o t he det rusor mot or neurons in t he int ermediolat eral cell
columns of t he sacral gray mat t er (S2–S4). Eff erent s f rom t he cort ical and
subcort ical mict urit ion cent ers descend by w ay of t he pyramidal t ract s t o t he
pudendal nuclei (O nuf 's nucleus) in t he sacral spinal cord (S2–S4). The pudendal
nerves, w hose mot or neurons are locat ed in t he vent ral horns of sacral segment s
S2–S4, innervat e t he st riat ed muscle around t he uret hra.
The cent ral sensorimot or pat hw ays concerned w it h mict urit ion and sphinct er
cont rol can t heref ore be summarized as f ollow s[77] :
1. Cort icospinal pat hw ays (f rom mot or cort ex t o pudendal mot or neurons) w hich
are concerned w it h t he volunt ary cont rol of t he sphinct ers and pelvic f loor.
2. The uret hral ref lex loop (f rom uret hral aff erent s t o pudendal mot or neurons),
w hich maint ains t he sphinct er t one w hen t he det rusor is inact ive.
3. The det rusor ref lex loop (det rusor aff erent s t o pudendal mot or neurons),
w hich causes sphinct er relaxat ion w hen t he det rusor is act ive.
4. The cord loop (f rom brainst em st ruct ures t o t he conus medullaris), w hich
coordinat es det rusor and sphinct er cont ract ion and relaxat ion.
5. The cerebral loop (involving t he brainst em, cerebral cort ex, and basal
ganglia st ruct ures), w hich init iat es and inhibit s sw it ching bet w een f illing and
voiding st at es.
As t he normal bladder f ills and urine is st ored (Fig. 5-5), cont ract ion of t he
det rusor muscle is inhibit ed. This inhibit ion requires int act pat hw ays bet w een t he
sacral cord and t he pont ine mict urit ion cent er[26] . Facilit at ion of act ivit y in t he
st riat ed uret hral sphinct er also occurs during f illing. Cont inence is promot ed by
bot h passive and ref lex act ivit ies. I n t he passive f illing phase, t he int ravesical
pressure init ially increases minimally ow ing t o t he elast ic propert y of t he smoot h
muscle and connect ive t issue in t he bladder w all; ret ent ion is maint ained at t his
low pressure because t he proximal uret hral pressure exceeds t he pressure w it hin
t he bladder. The cont inence ref lexes occur w hen t he int ravesical pressure begins
t o exceed t he pressure at t he uret hral orif ice. St imulat ion of f ront al mict urit ion
cent ers by bladder dist ent ion enhances sympat het ic act ivit y (t hrough hypogast ric
nerves), w hich result s in inhibit ion of t he det rusor muscle and cont ract ion of t he
int ernal uret hral sphinct er, as w ell as somat ic act ivit y (t hrough pudendal nerves),
w hich causes ext ernal sphinct er cont ract ion.
Voiding (Fig. 5-6) is normally a volunt ary act result ing f rom t he coordinat ed
relaxat ion of t he uret hral sphinct er and cont ract ion of t he det rusor. Bladder
f ullness st ret ches aff erent s t hat act ivat e t he pont ine mict urit ion cent er w hich, in
t urn, act ivat es t he det rusor ref lex and inhibit s t he sphinct er; t he pont ine cent er
coordinat es t he reciprocal relat ionship of t he det rusor and sphinct er and t he
ref lex organizat ion of f illing and voiding st at es[77] . Lesions bet w een t he pont ine
cent er and t he sacral cord int errupt pat hw ays t hat are inhibit ory t o t he det rusor
and t hose t hat coordinat e normal sphinct er–det rusor act ivit y[22, 26] . These
disorders may occur alone or in combinat ion and include t he hyperref lexic (ref lex
or spast ic) bladder, det rusor–sphinct er dyssynergia, poorly sust ained det rusor
cont ract ion, and increased post mict urit ion residual volume[26] .
FI G URE 5-5 Neural pat hw ay f or st orage of urine (+ = excit at ory; - =
inhibit ory)
FI G URE 5-6 Neural pat hw ays f or voiding (+ = excit at ory; - = inhibit ory)
The hyperref l exi c neurogeni c (spasti c) bl adder occurs w it h lesions above t he

level of t he sacral bladder cent er and below t he level of t he pont omesencephalic
mict urit ion cent er. I t occurs in condit ions causing quadriplegia or paraplegia and
in advanced cases of mult iple sclerosis. Loss of t he normal inhibit ion f rom higher
cent ers result s in det rusor cont ract ion during bladder f illing. The cont ract ions
may occur spont aneously or may be provoked by coughing or changing post ure.
I n most cases, t he det rusor becomes overact ive, so t here is urinary f requency,
urgency, urge
incont inence (t he pat ient is unable t o inhibit t he det rusor ref lex), and inabilit y t o
init iat e mict urit ion volunt arily. Small volumes of urine st imulat e uninhibit ed
det rusor muscle cont ract ion; t he bladder capacit y is reduced but residual urine
may be increased (increased post mict urit ion residual volume). The
bulbocavernosus and superf icial anal ref lexes are preserved. Wit h lesions above
t he splanchnic out f low, bladder f ullness may induce a “mass ref lex” w it h
paroxysmal hypert ension, headaches, diaphoresis, and bradycardia.
Simult aneous cont ract ion of t he sphinct er and t he det rusor during voiding
(detrusor–sphi ncter dyssynergi a) result s in obst ruct ed voiding, an int errupt ed
urinary st ream, incomplet e empt ying, and high int ravesical pressures because
t he sphinct er f ails t o relax correct ly[26] . Upper urinary t ract dilat at ion and kidney
damage may develop subsequent ly. Abnormal hyperref lexic cont ract ions may be
poorly sust ained and, in combinat ion w it h dyssynergia, result in incomplet e
empt ying.
Af t er acut e spinal cord injury, a variable period of spinal shock occurs during
w hich t he bladder is acont ract ile. Ref lex det rusor act ivit y ret urns in days t o
w eeks and ot her t ypes of bladder dysf unct ion (above) are t hen not ed, but spinal
shock persist s occasionally.
An autonomous neurogeni c bl adder (det rusor aref lexia) may be seen w it h
complet e lesions below t he T12 segment t hat involve t he conus medullaris and
cauda equina. I t occurs w it h sacral myelomeningocele and t umors of t he conus
medullaris–cauda equina region. This is also t he t ype of neurogenic bladder t hat
occurs during t he init ial shock phase of spinal cord injury. The bladder is
paralyzed, and t here is no aw areness of t he st at e of f ullness. I n most of t hese
cases, t here is urinary ret ent ion because t he t one of t he det rusor muscle is
abolished and t he bladder dist ends as urine accumulat es. I nabilit y t o init iat e
mict urit ion, overf low incont inence, and increased residual urine develop. There is
associat ed saddle anest hesia w it h absence of t he bulbocavernosus and
superf icial anal ref lexes. Anal sphinct er cont rol is of t en similarly aff ect ed.
St ret ch injury t o t he bladder w all (e. g. , ow ing t o anat omic obst ruct ion at t he
bladder neck or even volunt ary sphinct er cont ract ion) may cause dist ent ion of
t he bladder w all, decompensat ion of t he det rusor muscle, and event ually bladder
at onia. The bladder capacit y may great ly increase, and it s w alls may become
f ibrot ic. A large residual urine volume may t heref ore occur because of incomplet e
det rusor cont ract ions.
A motor paral yti c bl adder may be seen w it h lesions involving t he eff erent mot or
f ibers t o t he det rusor or t he det rusor mot or neurons in t he sacral spinal cord.
Some pat ient s develop a mot or paralyt ic bladder in associat ion w it h lumbar
spinal st enosis, lumbosacral meningomyelocele, or f ollow ing radical
hyst erect omy or abdominoperineal resect ion. I n most of t hese cases, pat ient s
suff er f rom painf ul urinary ret ent ion or impaired bladder empt ying. Residual urine
is markedly increased. The bulbocavernosus and superf icial anal ref lexes are
usually absent , but sacral and bladder sensat ion are present .
A sensory paral yti c bl adder may occur in t abes dorsalis, syringomyelia, or
diabet es mellit us. I t is caused by t he impairment of t he aff erent pat hw ays
innervat ing t he bladder or by t he dysf unct ion of t he post erior columns or lat eral
spinot halamic t ract at t he spinal cord level. Pat ient s maint ain volunt ary init iat ion
of mict urit ion. Urinary ret ent ion, overf low incont inence, or urinary t ract inf ect ion
may be early sympt oms. The bulbocavernosus and superf icial anal ref lexes may
be absent , decreased, or present .
Sexual Function
Neural and vascular mechanisms are closely int egrat ed in t he physiology of
erect ion. Erecti on has a psychogenic and a ref lex element ; t he ref lex cent er f or
erect ion is in t he conus medullaris[77] . The genit al organs are innervat ed by
t hree set s of peripheral nerves: (a) sacral parasympat het ic (pelvic nerves), (b)
t horacolumbar sympat het ic (hypogast ric and lumbar sympat het ic chain), and (c)
somat ic (pudendal nerves)[ 8] . The parasympat het ic syst em is considered t he
main eff ect or of penile erect ion (t hrough pelvic nerves), but t here is also
evidence f or a sympat het ic erect ile pat hw ay t hrough t he hypogast ric nerves[8] .
There is a sympat het ic erect ile (and ant ierect ile) out f low at about t he T12 spinal
cord level (w hich reaches t he genit alia t hrough t he hypogast ric nerves, t he pelvic
nerves, and t he pudendal nerves) and a parasympat het ic erect ile out f low at t he
S2–S3 level (parasympat het ic preganglionic f ibers pass t hrough t he pelvic
nerves t o t he pelvic plexus and innervat e t he corpora cavernosa t hrough
cavernous nerves). Descending erect ile (and probably ant ierect ile) pat hw ays
t ravel f rom t he cerebrum t hrough t he lat eral columns in t he spinal cord.
Theref ore, spinal cord lesions above T12 impair psychogenic erect ion, w hereas
lesions of t he conus medullaris or cauda equina abolish ref lex erect ion. I n men
w it h complet e spinal cord lesions below T12 t o L2 or w it h complet e cauda equina
lesions, psychogenic erect ion may occur t hrough t he sympat het ic out f low w hile
ref lex erect ion is absent [18] .
Limbic and hypot halamic pat hw ays, part icularly originat ing f rom t he medial
preopt ic ant erior hypot halamic area, are part icularly import ant in t he cont rol of
penile erect ion[8, 23] . Descending pat hw ays concerned w it h erect ion pass
t hrough t he medial f orebrain bundle t o t he midbrain t egment al region and t hen
t hrough t he vent rolat eral pons and lat eral f uniculus of t he cord t o t he
lumbosacral cent ers[55] .
Ejacul ati on is coordinat ed in a hypot het ical ejaculat ory ref lex cent er in t he T12–
L1 cord region t hat summat es t he descending excit at ory and inhibit ory impulses
and sensory impulses f rom t he glans and f renum[77] . The descending and
ascending pat hw ays are probably locat ed in t he lat eral columns. Spinal cord
lesions above t he T10 spinal level may cause an ejaculat ion, but a ref lex
ejaculat ion may be induced if t he aff erent (S2–S3) and eff erent (T10–L2)
pat hw ays are int act . Even ref lex ejaculat ion is not obt ained if t he cord lesion
dest roys t he T12–L2 levels[16, 77] .
Fecal Incontinence
The anal sphinct er mechanism comprises t he int ernal anal sphinct er (smoot h
muscle under aut onomic cont rol and account ing f or 80% of rest ing sphinct er
pressure[ 82] ), t he ext ernal anal sphinct er (slow -t w it ch st riat ed muscle innervat ed
by t he pudendal nerves), and t he puborect alis muscles (innervat ed by t he pelvic
branches of S3 and S4)[ 56] . The ext ernal sphinct er and t he puborect alis muscles
behave as a f unct ional unit , t he vol untary sphi ncter[ 68] . A spinal ref lex causes
t he st riat ed sphinct er t o cont ract during sudden increases in abdominal pressure
(e. g. , cough or sneeze)[ 67, 91] . Recept ors in t he pelvic f loor (not t he rect al
w all) det ect t he presence of st ool and are required f or f ecal cont inence[56] .
Theref ore, diabet es, pudendal neuropat hy, or cauda equina lesions may develop
overf low incont inence because of decreased rect al sensat ion[90, 98] . Wit h
diabet es, aut onomic neuropat hy and diabet ic diarrhea also cont ribut e t o f ecal
incont inence. Fecal incont inence, how ever, at least in t he elderly, is most of t en
caused by const ipat ion.
Fecal incont inence may t heref ore occur w it h disorders of t he sensory root s,
conus, mot or root s (S3–S4), or peripheral nerves. I n t hese condit ions, rect al
examinat ion may reveal reduced anal sphinct er t one, and t here may be
diminished perianal sensat ion and loss of t he anal skin ref lex (anal w ink). The
colon may be hypot onic and dist ended and t he anal sphinct er lax f rom
deaff erent at ion or deeff erent at ion. High spinal cord lesions may occasionally
cause f ecal incont inence; pat ient s w it h high spinal lesions usually have bet t er
sphinct er cont rol t han pat ient s w it h low lesions. Wit h cord lesions above t he
conus (and w it h some cerebral lesions), def ecat ion may be urgent and
precipit ant . Since t he same spinal segment s and nearly t he same spinal t ract s
subserve bot h bladder and bow el cont rol, spinal cord diseases may of t en cause
“double incont inence”; how ever, since t he bow el is less of t en f illed and it s
cont ent s usually solid, f ecal incont inence is usually less of a problem t han
urinary incont inence[1] .
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> Table of C ontents > C hapter 6 - C r anial Ner ve I ( The O lfac tor y Ner ve)
Chapter 6
Cranial Nerve I (The Olfactory Nerve)
Anatomy of The Olfactory Pathw ays

Alt hough t he olf act ory syst em is not of major import ance in neurologic diagnosis,
cert ain clinical inf ormat ion, usef ul in neuroanat omic localizat ion, may be at t ained
by invest igat ing t he sense of smell. This invest igat ion requires a basic
know ledge of t he anat omy of t he olf act ory pat hw ays [3, 6, 8, 28, 32] , especially
t heir relat ionship w it h t he surrounding neural st ruct ures (e. g. , f ront al lobes)
(Figs. 6-1 and 6-2).
The olf act ory recept ors, t he sensory cells of t he olf act ory epit helium, are
locat ed on t he superior–post erior nasal sept um and t he lat eral w all of t he nasal
cavit y. These ciliat ed cells give off cent ral processes t hat f orm small bundles
(approximat ely 20 in number). These bundles, t he f ilament s of t he olf act ory
nerve, penet rat e t he cribrif orm plat e of t he et hmoid bone and ent er t he olf act ory
bulb. Here, t he olf act ory aff erent f ibers synapse w it h t he dendrit es of t he
second-order neurons called t he mi tral and tuf ted cel l s. At t he point s of
synapse, conglomerat es of f ibers called t he ol f actory gl omerul i are f ormed. The
axons of t he mit ral and t uf t ed cells leave t he olf act ory bulb and course
post eriorly, as t he olf act ory t ract , in t he olf act ory sulcus on t he orbit al surf aces
of t he f ront al lobe. The olf act ory t ract divides int o a median and a lat eral
olf act ory st ria on eit her side of t he ant erior perf orat ed subst ance (t he t riangular
area f ormed by t he t w o st riae is called t he ol f actory tri gone). Some of t hese
st rial f ibers decussat e in t he ant erior commissure and join t he f ibers f rom t he
opposit e olf act ory pat hw ays, t erminat ing in t he cont ralat eral cerebral
hemisphere. O t her st rial f ibers, especially t hose of t he lat eral st ria, supply t he
ipsilat eral pirif orm lobe of t he cerebral (t emporal) cort ex (t he primary olf act ory
cort ex) and t erminat e in t he amygdaloid nucleus, sept al nuclei, and
hypot halamus.
Alt hough relat ively quant it at ive met hods [6, 28, 32] are available t o t est olf act ion
(e. g. , t est s of t he minimal percept ible odor or measurement s of olf act ory
f at igue), t he sense of smell is usually t est ed by asking t he pat ient t o sniff
various nonirrit at ing subst ances (each nost ril is t est ed separat ely) and t hen
at t empt t o ident if y t he odor (percept ion of t he smell is of more value t han
ident if icat ion of t he specif ic subst ance). I rrit at ing subst ances (e. g. , ammonia)
are t o be avoided because t hey st imulat e t he t rigeminal nerve f ibers in t he nasal
mucosa as w ell as t he olf act ory f ibers.
Localization of Lesions Affecting the Olfactory Nerve

Lesions Causing Anosmia
Anosmi a (loss of smell) or hyposmia (diminished olf act ory f unct ioning) may or
may not be apparent t o t he pat ient . He or she may have some diff icult y in t ast ing
various f lavors because t he ident if icat ion of t ast ed subst ances depends in part
on t he olf act ory syst em.
Local nasal disease (e. g. , allergic rhinit is, nasal obst ruct ion, polyposis) must
f irst be sought as t he cause of anosmia, especially if t he olf act ory diff icult y is
bilat eral. The most common cause of t ransient and bilat eral anosmia is t he
common cold. Af t er local nasal disease has been ruled out , anosmia, especially
unilat eral anosmia, should raise t he suspicion of a lesion aff ect ing t he olf act ory
nerve f ilament s, bulb, t ract , or st ria. Because t he cort ical represent at ion f or
smell in t he pirif orm cort ex is bilat eral, a unilat eral lesion dist al
t o t he decussat ion of t he olf act ory f ibers causes no olf act ory impairment .
FI G URE 6-1 The olf act ory nerve (lat eral view )
FI G URE 6-2 The olf act ory nerve (inf erior view )
Head injury [11, 31, 33] is probably t he most common cause of disrupt ion of t he
olf act ory f ibers prior t o t heir decussat ion. Front al impact produces less
dysf unct ion t han back or side impact s[11] . The olf act ory nerve proper (olf act ory
f ilament s) may be t orn by f ract ures involving t he cribrif orm plat e of t he et hmoid
bone, but closed head injury w it hout f ract ure may also disrupt t he olf act ory
pat hw ays unilat erally or bilat erally. Closed head injury can produce impairment
of olf act ory recogni ti on despit e relat ively preserved olf act ory detecti on[ 23] .
O lf act ory naming and recognit ion may be impaired by t raumat ic f orces aff ect ing
t he orbit of ront al and t emporal lobes, and t he degree of olf act ory dist urbances is
direct ly relat ed t o t he severit y of t he injury[23] . Dist urbances of complex
olf act ory f unct ion (e. g. , discriminat ion) despit e t he relat ively preserved det ect ion
of odors has been report ed w it h alcoholic Korsakoff 's syndrome[21] and
f ollow ing t halamic or pref ront al cort ical lesions[30] . Signif icant olf act ory
dysf unct ion has also been described w it h Alzheimer's disease [25, 26, 37] , Lew y
body disease[29] , Hunt ingt on's chorea (HC)[ 26] , mult iple sclerosis[10, 18] ,
Parkinson's disease (PD) [9, 19, 25, 34] , Ref sum's disease[15] , spinocerebellar
at axias (including Friedreich's at axia)[ 4] , and in adult s w it h Dow n's
syndrome[ 36] . Pat ient s w it h PD have decreased perf ormance on odor
discriminat ion t est s in addit ion t o def icit s of odor det ect ion and
ident if icat ion[ 34] . O lf act ory loss in pat ient s w it h mult iple sclerosis has been
associat ed w it h plaque f ormat ion in t he cent ral olf act ory (i. e. , inf erior f ront al and
t emporal) brain regions[10] .
Haw kes not ed t hat t here has been an increase of int erest in olf act ory
dysf unct ion because it w as realized t hat anosmia w as a common f eat ure of
idiopat hic PD and Alzheimer-t ype dement ia (AD)[ 17] . I n his review of PD,
parkinsonian syndromes, essent ial t remor, AD, mot or neuron disease (MND) and
HC, t he f ollow ing observat ions are made[17] :
1. O lf act ory dysf unct ion is f requent and of t en severe in PD and AD.
2. Normal smell ident if icat ion in PD is rare and should prompt t he review of
diagnosis unless t he pat ient is a f emale w it h a t remor-dominant disease.
3. Anosmia in suspect ed progressive supranuclear palsy and cort icobasal
degenerat ion is at ypical and should likew ise provoke diagnost ic review.
4. Hyposmia is an early f eat ure of PD and AD and may precede mot or and
cognit ive signs respect ively.
5. Subject s w it h anosmia and one apoE4 allele have an approximat e f ivef old
increased risk of lat er AD.
6. I mpaired sense of smell is seen in some pat ient s at 50% risk of
parkinsonism.
7. Smell t est ing in HC and MND, w here abnormalit y may be f ound, is not likely
t o be of clinical value.
8. Biopsy of olf act ory nasal neurons show s nonspecif ic changes in PD and AD
and, at present , w ill not aid diagnosis.
Congenit al anosmia or hyposmia may occur ow ing t o clef t palat e in men, absent
or hypoplast ic olf act ory bulbs or t ract s[27] , f amilial dysaut onomia, and Turner's
syndrome. A f amilial syndrome of permanent anosmia w it h hypogonadot ropic
hypogonadism (Kallmann's syndrome) has also been described[40, 41] ; pat ient s
w it h t his syndrome may also have cerebellar at axia and mirror movement s of t he
hands[ 16] .
O lf act ory discriminat ion and det ect ion may be abnormal af t er unilat eral f ront al or
t emporal lobect omy[42] . Af t er t emporal lobect omy, def icit s in olf act ory
discriminat ion are conf ined t o t he nost ril ipsilat eral t o t he lesion. Af t er f ront al
lobect omy, discriminat ion is also impaired; how ever, in pat ient s w it h right f ront al
lesions including t he orbit al cort ex, t he impairment is f ound in bot h nost rils.
Theref ore, t he orbit of ront al cort ex is import ant in olf act ory discriminat ion, and
t he nost ril diff erence f ound in healt hy subject s, t oget her w it h t he birhinal
impairment in pat ient s w it h right orbit of ront al damage, suggest s a relat ive
advant age of t he right orbit al region in olf act ory processing[42] . Anosmia may
also complicat e rhinoplast y, et hmoidect omy, laryngect omy, submucous resect ion
of t he nasal sept um, radiot herapy[28] , and surgery f or ant erior communicat ing
art ery aneurysms ow ing t o t he olf act ory nerve dysf unct ion[13] . O lf act ory damage
is much more common af t er an ant erior int erhemispheric surgical approach
rat her t han af t er a basal int erhemispheric approach.
The olf act ory bulb and t ract are f requent ly aff ect ed by t umors of t he olf act ory
groove (especially meningiomas)[ 39] , w hich may cause t he Foster Kennedy
syndrome (see t he discussion on Fost er Kennedy Syndrome). Tumors of t he
sphenoid or f ront al bone (e. g. , ost eomas), pit uit ary t umors w it h suprasellar
ext ension, nasopharyngeal carcinoma[35] , and saccular aneurysms of t he
ant erior port ion of t he circle of Willis (e. g. , a giant ant erior communicat ing art ery
aneurysm)
may also compress t he olf act ory bulb or t ract [24] . Any diff use meningeal
process (e. g. , meningit is) may involve t he olf act ory pat hw ays. The anat omic
relat ionship of t he f ront al lobe t o t he olf act ory bulb and t ract is especially
import ant . Mass lesions of t he f ront al lobe (e. g. , glioma or abscess) of t en exert
pressure on t he olf act ory syst em and may lead t o anosmia even bef ore clear-cut
f ront al lobe signs and sympt oms are not ed. Theref ore, in any pat ient w it h
personalit y changes or subt le signs of f ront al lobe involvement , olf act ion should
be caref ully t est ed.
TABLE 6-1 Conditions Associated w ith Disturbance of

Olfaction
Congenital
Cleft palate (in men)
Down's syndrome
Familial dysautonomia
Kallmann's syndrome
Turner's syndrome
Endocrine/Metabolic
Adrenal insufficiency
Diabetes mellitus
Hypothyroidism
Pseudohypoparathyroidism
Iatrogenic
Ethmoidectomy
Hypertelorism procedures
Orbitofrontal lobectomy
Postlaryngectomy
Radiotherapy
Rhinoplasty
Submucous resection, nasal septum
Temporal lobectomy
Infectious
Herpes simplex meningoencephalitis
HIV infection
Upper respiratory tract, viral
Liver disease
Acute viral hepatitis
Cirrhosis
Local processes
Hansen's disease
Nasal obstruction (adenoid hypertrophy, large inferior
turbinates)
Polyposis
Rhinitis
Sjögren's syndrome
Tumors
Neurologic
Alzheimer's disease
Head trauma
Huntington's disease
Korsakoff's syndrome
Multiple sclerosis
Meningiomas
Giant anterior communicating artery aneurysm
Migraines
Parkinson's disease
Spinocerebellar ataxias, including Friedreich's ataxia
Seizure disorders
Temporal lobe tumors
Refsum's disease
Psychiatric
Hypochondriasis
Major depression
Post-traumatic stress disorder
Schizophrenia
Uremia/Dialysis
Miscellaneous
Cystic fibrosis
Giant cell arteritis
Occupational exposure
Sarcoidosis
HIV = human immunodeficiency virus.

Modified from Mott AE, Leopold DA. Disorders of taste
and smell. Med Clin North Am 1991;75:1321–1353.
Esthesi oneurobl astomas (olf act ory neuroblast omas) are t umors t hat arise in t he
upper nasal cavit y, of t en superior and lat eral near t he et hmoid sinus[27] . These
t umors may present w it h anosmia as w ell as persist ent nasal obst ruct ion and
epist axis[ 27] . They may occasionally involve
t he orbit and cause periorbit al sw elling, propt osis, diplopia, and visual loss[2,
27] .
The Foster Kennedy Syndrome

The Fost er Kennedy syndrome is occasionally not ed w it h olf act ory groove or
sphenoid ridge masses (especially meningiomas) or space-occupying lesions of
t he f ront al lobe. This syndrome consist s of t he f ollow ing t hree signs:
1. Ipsi l ateral anosmi a due t o direct pressure on t he olf act ory bulb or t ract
2. Ipsi l ateral opti c atrophy due t o direct injury of t he ipsilat eral opt ic nerve
3. Contral ateral papi l l edema due t o raised int racranial pressure secondary t o
t he mass lesion
Many cases of Fost er Kennedy syndrome may act ually be due t o direct bilat eral
opt ic nerve compression; even increased int racranial pressure w it hout opt ic
nerve compression may cause t he syndrome[38] .
A pseudo–Foster Kennedy syndrome may rarely be not ed w hen increased
int racranial pressure of any cause occurs in a pat ient w ho has previous unilat eral
opt ic at rophy. Because t he at rophic disc cannot become sw ollen, only t he
previously normal f undus demonst rat es papilledema. O lf act ory nerve involvement
varies depending on t he et iology of t he increased int racranial pressure, but
increased int racranial pressure per se may impair olf act ion w it hout any evidence
of local olf act ory pat hw ay damage. A pseudo–Fost er Kennedy syndrome is most
of t en due t o sequent ial ant erior ischemic opt ic neuropat hy (art erit ic or
nonart erit ic) or opt ic neurit is in w hich opt ic disc edema on one side is associat ed
w it h opt ic disc at rophy on t he ot her side.
Lesions Causing Parosmia and Cacosmia

Parosmia or dysosmia (perversion of smell) and cacosmia (experiencing
unpleasant odors)[ 7] are rare phenomena t hat are usually seen af t er a head
injury or w it h a psychiat ric disease (e. g. , depression). Various scent s are
int erpret ed as “abnormal” and, of t en, unpleasant . O ccasionally, t hese unpleasant
odors may persist or occur spont aneously as an olf act ory hallucinat ion[12, 22] .
I t is not clear w het her t hese phenomena are of cort ical origin (due t o primary
olf act ory cort ex injury), and t heref ore possibly ict al in nat ure, or are due t o
direct irrit at ion of t he olf act ory pat hw ays. Unilat eral paroxysmal olf act ory
hallucinat ions (paroxysmal unilat eral dysosmia) have been cured by resect ion of
t he homolat eral olf act ory bulb suggest ing t hat , in at least some pat ient s,
olf act ory hallucinat ions may be due t o st ruct ural nerve damage[22] . O lf act ory
hallucinat ions (especially f oul odors) may occur w it h part ial seizures w it h
complex sympt omat ology or w it h migraine[1, 14] . O lf act ory epilept ic auras are
not necessarily unpleasant [1] . I n pat ient s w it h olf act ory epilept ic auras, t umors
are t he most common et iology of t he seizures, and mesial t emporal sclerosis is
relat ively rare; t he amygdala is t he most likely sympt omat ogenic zone in t hese
pat ient s[ 1] . Hyperosmia (increased sensit ivit y t o smell) may occur w it h migraine
or hyperemesis gravidarum; phant ososmia ref ers t o t he percept ion of an odor
w hen none is present [5] .
Hyposmia and parosmia have been associat ed w it h hypogeusia (diminished t ast e
acuit y) and dysgeusia (dist ort ed t ast e percept ion) and have been correlat ed w it h
zinc and vit amin A def iciencies[20] . O t her condit ions associat ed w it h alt ered
olf act ion include adrenal insuff iciency, diabet es mellit us, hypot hyroidism,
pseudohypoparat hyroidism, cyst ic f ibrosis, and sarcoidosis[28] .
Condit ions associat ed w it h dist urbances of olf act ion are out lined in Table 6-1.
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1279 and 1337–1343.
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> Table of C ontents > C hapter 7 - Vis ual P athw ays
Chapter 7
Visual Pathways
Anatomy of the Visual System

The Retina
The ret ina ext ends ant eropost eriorly f rom t he ora serrat a t o t he opt ic disc, w hich
corresponds t o t he at t achment of t he opt ic nerve, slight ly nasal t o t he post erior
pole of t he eyeball. Approximat ely at t he post erior pole of t he globe is t he
macula, a circular area of t he ret ina t hat appears yellow w hen view ed w it h t he
opht halmoscope. Each ret ina can be divided int o f our quadrant s by a vert ical and
a horizont al meridian int ersect ing at t he macula (Fig. 7-1). The horizont al
meridian separat es t he ret ina int o superior and inf erior port ions. The vert ical
meridian separat es t he nasal (medial) ret ina f rom t he t emporal (lat eral) ret ina.
The f irst neuronal element s in t he visual syst em are locat ed deep in t he ret ina,
separat ed f rom t he choroid by t he ret inal pigment epit helium. These element s,
t he rods and cones, cont ain pigment s t hat , react ing t o visible light , produce
elect rical act ivit y. This act ivit y is conveyed t o t he more superf icially locat ed
ganglion cells by short bi pol ar cel l s and by horizont ally disposed amacri ne cel l s
(Fig. 7-2). The gangl i on cel l s send t heir axons predominant ly t o t he lat eral
geniculat e body or t o t he superior colliculus.
The phot orecept ors, rods and cones, are orient ed t ow ard t he pupillary opening
rat her t han t ow ard t he cent er of t he globe. The pigment of t he rods is a
glycoprot ein called rhodopsi n, w hich react s t o light w it hin t he visible w avelengt h,
f rom 400 t o 800 nm. Approximat ely 100 million rods are unevenly dist ribut ed
t hroughout t he ret ina. They become more t ight ly packed in t he f undus of t he
globe but are absent f rom t he opt ic disc (blind spot ) and f rom t he macula.
There are t hree diff erent t ypes of cones t hat react maximally t o red, green, or
blue light . The ret ina cont ains approximat ely 7 million cones, 100, 000 of w hich
are concent rat ed in t he macular region. I n t he cent er of t he macula t here is a
small region (t he f oveola, measuring 0. 35 mm across) t hat is devoid of vessels
and neural element s ot her t han t he t ight ly packed cones. Visual discriminat ion is
great est here, w here light can reach t he phot orecept ors avoiding t he layers
present in t he rest of t he ret ina.
An est imat ed 1. 2 million ganglion cells populat e t he inner aspect of t he ret ina.
Their recept ive f ields become smaller in t he region of t he post erior pole of t he
globe, w here ganglion cells are much more numerous t han in t he periphery and
t he cones have one-t o-one connect ions w it h t heir ow n ganglion cells. By
cont rast , in t he periphery, recept ive f ields overlap ext ensively. This anat omic
arrangement may explain t he relat ive sparing of t he peripheral vision w it h lesions
t hat aff ect t he ganglion cells pref erent ially.
Morphologically diff erent classes of ret inal ganglion cells (M cells and P cells)
project t o diff erent divisions of t he lat eral geniculat e nucleus, w hich, in t urn,
project t o t he visual cort ex in a segregat ed dist ribut ion. M cells make up
approximat ely 10% of t he ret inal ganglion cells and are engaged w it h “w here”
t he t arget of regard is in space. They are concerned w it h dept h percept ion or
st ereopsis, are color ignorant , and have high cont rast sensit ivit y, low spat ial
resolut ion, and f ast t emporal resolut ion. Ret inal M cells project t o magnocellular
neurons in layers 1 and 2 of t he lat eral geniculat e nucleus, w hich in t urn project
t o 4C α neurons in cort ical area 17. The 4C α neurons project t o 4 β cort ical
area 17 neurons, w hich in t urn project t o cort ical area MT (see Chapt er 8).
P cells only slight ly out number M cells in t he peripheral ret ina, w hereas t he
macula is composed predominant ly of P cells, w hich are concerned w it h “w hat is
being seen” (t hey have color opponency, low cont rast sensit ivit y, and high spat ial
resolut ion). P cells make up approximat ely 90% of ret inal ganglion cells and
project t o parvocellular neurons in layers 3, 4, 5, and 6 of t he lat eral geniculat e
nucleus, w hich project t o 4C β neurons in cort ical area 17. The 4C β neurons
project t o layers 2 and 3 of cort ical area 17 w hich, in t urn, project t o cort ical
area 18, w hich t hen sends f ibers t o areas V3 and V4 [47] .
FI G URE 7-1 Ret inal nerve f iber layer and art eries. Not e t he t emporal raphe
f ormed by t he f ibers f rom t he superior and inf erior ret ina.
Cert ain pat hologic processes may pref erent ially aff ect M cells or P cells. I n
Alzheimer's disease, f or example, t here is a predominant loss of M cells in t he
ret ina, result ing in diff icult y w it h det ermining mot ion and dept h and inaccurat e
f ast eye movement s (saccades) w it h preserved acuit y and color vision [150] . I n
opt ic neurit is (O N), more P t han M ganglion cells are lost , w hich may explain
cont rast sensit ivit y abnormalit ies, cent ral scot omat a, and color vision impairment
[ 177] .
The axons of t he ganglion cells const it ut e t he innermost layer of t he ret ina,
w hich is separat ed f rom t he vit reous by a t hin basement membrane. The posit ion
of t he axons in t he nerve f iber layer depends on t heir origin in t he ret ina. As t he
axons converge t ow ard t he opt ic disc, t he ganglion cells closer t o t he disc send
t heir axons t hrough t he w hole t hickness of t he nerve f iber layer. Theref ore, t he
more peripherally generat ed axons are deeper in t his layer, w hereas t he ones
originat ing cent ripet ally rest nearer t o t he vit reous (Fig. 7-2. )
Nerve f ibers nasal t o t he opt ic disc and t hose originat ing in t he nasal side of t he
macula (papillomacular bundle) t ake a st raight course as t hey converge int o t he
opt ic disc (Fig. 7-1). The remaining f ibers arch around t he papillomacular bundle,
adopt ing a disposit ion t hat has a bearing on t he visual f ield def ect s t hat are
secondary t o ret inal and opt ic nerve lesions. Fibers f rom t he superior half of t he
t emporal aspect of t he macula arch superiorly and t hen dow n t ow ard t he disc.
Fibers f rom t he inf erior half of t he t emporal aspect of t he macula arch inf eriorly
and t hen ascend t o reach t he disc. Fibers f rom t he t emporal ret ina, part icularly
t hose closer t o t he horizont al meridian, f ollow a similar course. Theref ore,
bet w een t he nerve f ibers f rom t he superior t emporal ret ina and t hose f rom t he
inf erior t emporal ret ina a raphe is f ormed, locat ed in t he horizont al meridian
(Fig. 7-1).
The axons of t he ganglion cells on t he t emporal side of a vert ical line draw n
t hrough t he f ovea project t o t he ipsilat eral lat eral geniculat e body, w hereas t he
ones f rom t he nasal side cross at t he opt ic chiasm (Fig. 7-3). How ever, t his
separat ion
is not sharp. The neurons subserving t he macular region and a vert ical st rip of
approximat ely 1 degree, cent ered in t he f ovea, project t o eit her lat eral
geniculat e body.
FI G URE 7-2 Diagrammat ic represent at ion of t he ret inal layers, disposit ion of
f ibers in t he nerve f iber layer and opt ic nerve, and visual f ield def ect s
caused by ret inal or opt ic nerve lesions. The vert ical bars (a, b, c) represent
part ial (a) t o complet e (c) ret inal lesions; t he corresponding f ield def ect s are
depict ed underneat h. Ret inal lesions aff ect ing t he nerve f iber layer have an
arcuat e shape w it h t he base locat ed peripherally and, in t emporal ret inal
lesions, in t he horizont al meridian. Compare w it h Figure 7-1.
The Optic Nerves and Optic Chiasm

Each opt ic nerve is approximat ely 50 mm long and has f our port ions f rom t he
globe t o t he chiasm (Fig. 7-4).
1. Intraocul ar Porti on. I n t his port ion, also called t he opt ic nerve head (1 mm
long), t he axons become myelinat ed (cent ral t ype of myelin). The
f unduscopic appearance of t he opt ic nerve depends on t he angle of t he nerve
head t o t he eye. When t he angle bet w een t he nerve and t he sclera is <90
degrees, a rim or crescent of choroid or sclera may be seen on t he f lat
t emporal side of t he disc, w hereas t he nasal edge appears elevat ed.
2. Intraorbi tal Porti on. This (sect ion 25 mm long) is shaped like an elongat ed S
t o allow mobilit y w it hin t he orbit . Here t he opt ic nerve is surrounded by f at
cont ained in t he cone f ormed by t he ocular muscles. The apex of t his cone
(w hich is open t o t he opt ic f oramen and t he superior orbit al f issure) is
direct ed post eriorly and slight ly displaced nasosuperiorly in t he orbit (Fig. 7-
4). I n addit ion t o t he opht halmic art ery, t he ciliary ganglion and nerves, and
t he nerves t o t he ext raocular muscles are in close relat ion t o t he opt ic nerve
here.
FI G URE 7-3 Schemat ic horizont al sect ion at t he level of t he lat eral

geniculat e bodies, depict ing t he opt ic pat hw ays. The right hemif ield has
been shaded, and f ibers f rom t he corresponding ret ina have been t raced.
3. Intracanal i cul ar Porti on. This port ion (approximat ely 9 mm long) is t he part
of t he nerve t hat t ravels t he opt ic canal. Each opt ic canal is orient ed
post erosuperomedially, at an angle t hat approximat es 45 degrees t o t he
sagit t al and horizont al planes. The opht halmic art ery and some f ilament s of
t he sympat het ic carot id plexus accompany t he opt ic nerve w it hin t he opt ic
canal.
4. Intracrani al Porti on. This part (approximat ely 4–16 mm long, depending on
t he posit ion of t he chiasm) st ret ches bet w een t he proximal opening of t he
opt ic canal and t he chiasm (Fig. 7-4). Each opt ic nerve lies above t he
respect ive carot id art ery as t his vessel exit s f rom t he cavernous sinus and
gives off t he opht halmic art ery. I nf eromedially, t he opt ic nerve lies over t he
bony roof of t he sphenoid sinus, w hich can be quit e t hin, and over t he
cont ent s of t he sella t urcica w hen t he chiasm is post eriorly placed. Superior
t o each opt ic nerve is t he horizont al port ion of t he ant erior cerebral art ery,
w hich is overlaid by t he gyrus rect us of t he f ront al lobe, t he olf act ory t ract ,
and t he ant erior perf orat ed subst ance (Fig. 7-5). The ant erior communicat ing
art ery is superior t o t he opt ic nerves or t o t he opt ic chiasm.
Proximal t o t he angled opt ic canal, t he opt ic nerves maint ain a 45-degree angle
t o t he horizont al plane, and t he chiasm is similarly t ilt ed over t he sella t urcica,
w it h t he suprasellar cist ern lying bet w een t hem. The relat ion bet w een t he chiasm
and t he sella varies bet w een individuals. I n brachycephalic heads t he chiasm
t ends t o be more ant erior and dorsal t han in dolichocephalic heads. Aut opsy
st udies have show n t hat in approximat ely 5% of individuals t he chiasm overlies
t he ant erior margin of t he sella (pref i xed chi asm), in 12% it lies over t he
diaphragma sellae, in 79% it is above t he dorsum sellae, and in 4% it project s
behind t he dorsum sellae (postf i xed chi asm). The chiasm is locat ed below t he
suprachiasmat ic recess of t he t hird vent ricle in close proximit y t o t he
hypot halamus. Above t he chiasm are t he lamina t erminalis and t he ant erior
commissure. I mmediat ely post erior t o it , t he pit uit ary st alk runs an ant eroinf erior
course. The opt ic t ract s originat e f rom t he post erolat eral corners of t he chiasm
(Fig. 7-5).
FI G URE 7-4 Superolat eral view of t he cont ent s of t he sella and cranial
nerves in t he cavernous sinus.
Nerve f ibers in t he opt ic nerve f ollow a t opical arrangement similar t o t hat f ound
in t he ret ina (Fig. 7-6). Superior ret inal f ibers run superiorly in t he opt ic nerve,
inf erior f ibers are below, and t hose f rom t he t emporal and nasal ret ina run in t he
corresponding part s of t he opt ic nerve. I n t he proximal port ion of t he nerve, near

t he globe, t he macular f ibers occupy a w edge-shaped sect or just t emporal t o t he
cent ral vessels (Fig. 7-6). More dist ally, t hey shif t t ow ard t he core of t he nerve.
FI G URE 7-5 I nf erior aspect of t he brain show ing some relat ionships of t he
opt ic nerves, chiasm, and opt ic t ract s.
FI G URE 7-6 Disposit ion of t he ganglion cell axons in a cross-sect ion of t he

opt ic nerve. A: Dist al port ion, near t he globe. B: Proximal port ion, w here t he
macular f ibers have shif t ed t o t he core of t he nerve.
At t he chiasm, more t han half of t he f ibers (t hose originat ing in ganglion cells of
t he nasal ret ina) cross t o reach t he cont ralat eral opt ic t ract (Fig. 7-3). The rat io
of crossed t o uncrossed f ibers is approximat ely 53: 47. Fibers f rom t he inf erior
part of t he nasal ret ina are vent ral in t he chiasm and loop int o t he proximal
port ion of t he cont ralat eral opt ic nerve (Wi l brand's knee) bef ore reaching t he
lat eral aspect of t he opt ic t ract (Fig. 7-7). Those f rom t he superior nasal ret ina
remain dorsal in t he chiasm and become medial in t he opt ic t ract .
FI G URE 7-7 Crossing of nasal f ibers in t he opt ic chiasm. Fibers f rom t he
inf erior ret ina make a f orw ard loop int o t he opposit e opt ic nerve (Wilbrand's
knee). The exist ence of Wilbrand's knee has recent ly been quest ioned (see
t ext ). (Figure modif ied f rom Hoyt WF and Luis O . Visual f iber anat omy in t he
inf rageniculat e pat hw ay of t he primat e. Uncrossed and crossed ret inal
quadrant f iber project ions st udied w it h Naut a silver st ain. Arch O phthal mol
1962; 68: 94–138. )
The anat omic exist ence of Wilbrand's knee has come int o quest ion. Wilbrand
w as rest rict ed t o examining human subject s w ho had undergone enucleat ion. I n
t he enucleat ed eye, t he nerve f ibers at rophied and became dist inct f rom t he
nerve f ibers of t he normal eye as seen on myelin st aining. Hort on, ut ilizing axon
labeling t echniques in nonenucleat ed monkeys, w as unable t o demonst rat e
crossing f ibers looping int o t he cont ralat eral opt ic nerve (Wilbrand's knee) [70] .
I n one monkey t hat had undergone enucleat ion 4 years previously, how ever,
nerve f iber t opography similar t o t hat described by Wilbrand w as f ound. Hort on
hypot hesized t hat Wilbrand's knee may be an art if act of enucleat ion caused by
at rophy of t he opt ic nerve and not a normal anat omic f inding. How ever, t he
concept of Wilbrand's knee is st ill clinically usef ul (see subsequent t ext ).
Uncrossed f ibers, originat ing f rom t he t emporal ret ina, maint ain t heir dorsal or
vent ral posit ion in t he chiasm. The macular f ibers, w hich const it ut e a large
proport ion of t he t ot al number of chiasmal f ibers, are also crossed and
uncrossed. How ever, t he separat ion bet w een t emporal and nasal ganglion cells
is not sharp. Crossed and uncrossed f ibers originat e in bot h nasal and t emporal
sides of t he macula. I n t he opt ic t ract , t he macular f ibers occupy a dorsal
posit ion.
The Optic Tracts and Lateral Geniculate Bodies

The opti c tracts ext end f rom t he dorsolat eral corners of t he chiasm t o t he lat eral
geniculat e bodies. From t he chiasm t he t ract s run post erolat erally, limit ing t he
hypot halamus t o a t riangular space; t hey t hen sw eep around t he cerebral
peduncles, and, as soon as t hey cross t hem, reach t he lat eral geniculat e bodies
in t he post erior part of t he vent ral aspect of t he t halami (Fig. 7-3). Several large
vessels are locat ed below t he opt ic t ract s. The post erior communicat ing art ery
crosses t heir dist al port ion in t he suprasellar cist ern. I n t he perimesencephalic
cist ern, t he post erior cerebral art ery and t he basilar vein of Rosent hal are
apposed t o t he t ract s. I nf erolat erally, t he uncus of t he t emporal lobe covers t he
proximal port ion of each t ract (Fig. 7-5).
The l ateral geni cul ate body, a t halamic nucleus, provides a relay st at ion f or all
t he axons of t he ret inal ganglion cells subserving vision. Neurons f rom t he lat eral
geniculat e body project , by w ay of t he opt ic radiat ions, t o t he pericalcarine
cort ex of t he occipit al lobe, w hich is t he primary cort ical area f or vision (Fig. 7-
3). The lat eral geniculat e body is in t he roof of t he perimesencephalic cist ern
(cist erna ambiens), just medial t o t he hippocampal gyrus of t he t emporal lobe.
Ant eriorly, t he lat eral geniculat e body receives t he opt ic t ract and sends out t he
vent ral opt ic radiat ions, w hich lie in close associat ion w it h t he post erior limb of
t he int ernal capsule. Dorsolat erally, t he lat eral geniculat e body is covered by t he
opt ic radiat ions. Dorsomedial t o t he lat eral geniculat e body, t he audit ory
radiat ions, originat ing f rom t he medial geniculat e body, pass on t heir w ay t o t he
t ransverse t emporal gyrus of Heschl, w here t he primary audit ory cort ex is
locat ed. Superomedial t o t he lat eral geniculat e body is t he pulvinar of t he
t halamus.
Shaped on midsect ion like Napoleon's hat , w it h it s concave aspect (hilus) f acing
inf eropost eromedially, t he lat eral geniculat e body has a deep brow n color w it h
st ripes (st riae) of w hit e mat t er t hat are visible t o t he naked eye [74] . The
geniculat e neurons, as numerous as t he f ibers in t he opt ic t ract , are disposed in
six laminae, numbered f rom I t o VI , beginning f rom t he hilus of t he nucleus.
Layers I , I V, and VI serve t he cont ralat eral eye, w hereas I I , I I I , and V are
connect ed w it h t he ipsilat eral eye. These six laminae are clearly dist inguished in
t he cent er of t he lat eral geniculat e body, w here t he macular region of t he ret ina
is represent ed, but only one or t w o are present in t he peripheral part of t he
nucleus, w hich receives axons f rom ganglion cells in t he peripheral ret ina.
The post chiasmal shif t in t he posit ion of t he f ibers (t he superior ret inal f ibers
become superomedial and t he inf erior f ibers become inf erolat eral; Fig. 7-7)
persist s in t he synapt ic areas of t he lat eral geniculat e body. This shif t is
st raight ened out in t he opt ic radiat ions, w here again t he superior f ibers
correspond t o t he superior ret ina and t hose below t o t he inf erior ret ina. A similar
represent at ion is f ound in t he calcarine cort ex.
The Optic Radiations

The opt ic radiat ions sw eep post eriorly around t he lat eral aspect of t he post erior
port ion of t he lat eral vent ricles (Fig. 7-8), f orming t he ext ernal sagit t al st rat um,
w hich is separat ed f rom t he vent ricle by t he int ernal sagit t al st rat um, made up of
occipit omesencephalic f ibers. Three bundles can be dist inguished in t he
radiat ions: (a) t he upper bundle, originat ing in t he medial part of t he lat eral
geniculat e body and corresponding t o t he superior ret ina, w hich courses t hrough
t he deep pariet al w hit e mat t er and ends in t he superior lip of t he calcarine
f issure; (b) t he cent ral bundle, originat ing f rom t he medial part of t he nucleus
and serving t he macular region, w hich t ravels t hrough t he post erot emporal and
occipit al w hit e mat t er and ends in t he post erior part of t he calcarine f issure, on
bot h lips; and (c) t he low er bundle, originat ing f rom t he lat eral part of t he
nucleus and corresponding t o t he low er ret ina, w hich sw eeps f irst ant eriorly and
t hen post eriorly around t he t emporal horn of t he lat eral vent ricle (Fig. 7-8),
t erminat ing in t he low er lip of t he calcarine f issure. As t hey sw eep lat eral t o t he
vent ricle (Meyer's l oop), t he low er radiat ions reach a point locat ed
approximat ely 5 cm behind t he t ip of t he t emporal lobe.
FI G URE 7-8 Lat eral view of t he brain show ing t he arrangement of t he opt ic
radiat ions in t he pariet al and t emporal lobes, lat eral t o t he vent ricular
syst em.
I n t he ant erior part of t he radiat ions, f ibers corresponding t o adjacent ret inal
unit s are spat ially separat ed and t he macular f ibers, inst ead of being int erposed
bet w een f ibers f rom t he superior and inf erior peripheral ret ina, run medial t o
t hem. Also, f ibers f rom eit her eye seem t o have a similar ant erior ext ent in
Meyer's loop, w it h t hose f rom t he cont ralat eral eye lying medial t o t he ones
coming f rom t he ipsilat eral eye.
The Visual Cortex and Visual Association Areas

Cort ical area 17 of Brodmann, locat ed along t he superior and inf erior lips of t he
calcarine f issure in t he medial aspect of t he occipit al lobe, receives t he axons
f rom t he neurons of t he lat eral geniculat e body and represent s t he f irst link in
t he cort ical processing of visual inf ormat ion (primary visual cort ex, see Chapt er
20). The primary visual cort ex act ually ext ends f art her t han t he post erior ext ent
of t he calcarine f issure, spreading f or approximat ely 1 cm around t he
post erolat eral aspect of t he occipit al pole. O n cross-sect ion of t he cort ex, a
w hit e mat t er st ria (stri a G ennari) can be seen w it h t he naked eye. This
charact erist ic f eat ure has w on t he t erm stri ate cortex f or area 17. The line of
G ennari corresponds t o a t hick band of w hit e mat t er in layer I V of t he cort ex,
w hich is devoid at t his point of pyramidal cells but is very rich in granular cells.
Each occipit al lobe receives project ions f rom t he nasal half of t he opposit e eye
and f rom t he t emporal half of t he ipsilat eral ret ina. More simply, it receives
project ions f rom t he t w o halves of t he ret inas on t he same side as t he occipit al
lobe (Fig. 7-3). This unilat eral represent at ion includes t he macular region. The
superior and inf erior ret inal project ions ext end t o t he superior and inf erior lips of
t he calcarine f issure, respect ively. Finally, t he macular ret ina is represent ed in
t he post erior pole of t he calcarine cort ex, w hereas t he more peripheral ret ina is
more ant eriorly represent ed [161] . The f oveal represent at ion is locat ed at t he
occipit al pole, w here t he st riat e cort ex usually ext ends approximat ely 1 cm ont o
t he lat eral convexit y of t he occipit al lobe. The ext reme periphery of t he visual
f ield is represent ed ant eriorly at t he junct ion of t he calcarine and pariet o-
occipit al f issures. The cent ral 10 t o 15 degrees of vision f ill most of t he t ot al
surf ace area of t he occipit al cort ex (as much as 50%-60%) (Figs. 7-9 and 7-10)
[ 73, 116] .
FI G URE 7-9 Schemat ic diagram show ing arrangement of V1, V2, and V3
along t he medial and post erior occipit al surf ace. Most of V1 is buried w it hin
t he calcarine f issure. (From Hort on JC, Hoyt WF. The represent at ion of t he
visual f ield in human st riat e cort ex. A revision of t he classic Holme's map.
Arch O phthal mol 1991; 109: 816 . Copyright 1991, American Medical
Associat ion. Reprint ed w it h permission. )
Vascular Supply of the Visual Pathways

The vascular supply of t he ret ina is derived f rom t he opht halmic art ery, w hich
branches f rom t he carot id art ery short ly af t er t his vessel exit s f rom t he
cavernous sinus. At t he opt ic canal, t he opht halmic art ery lies below and lat eral
t o t he nerve. At a point 5 t o 15 mm f rom t he globe, it gives off t he cent ral ret inal
art ery, w hich pierces t he opt ic nerve and courses f orw ard in it s core, t o divide
int o a superior and an inf erior branch
at t he opt ic disc (Fig. 7-1). Second-order nasal and t emporal branches supply
t he nerve f iber layer and t he inner layers of t he ret ina (including ganglion cells).
From t he anat omic arrangement of t hese vessels, it f ollow s t hat t he complet e
occlusion of t he cent ral ret inal art ery result s in global ret inal ischemia, except
w hen t he macular area is supplied by cilioret inal art eries, and occlusion of one
of it s branches causes superior or inf erior ret inal ischemia. The consequence of
such a lesion is an inf erior or superior alt it udinal f ield def ect (Fig. 7-2).
I nf arct ion in t he t errit ory of t he cent ral ret inal art ery may be caused by emboli,
t hrombi, hypercoagulable st at es, migraine, and art erit is (e. g. , giant cell
art erit is).
FI G URE 7-10 A: Art if icially f lat t ened map show ing ret inot opic organizat ion of
V1 (st ippled area), V2 (small t riangles), and V3 (hat ched) in t he lef t occipit al
lobe. B: Right visual f ield coordinat es corresponding t o map in (A). More
t han half of t he visual cort ex is devot ed t o processing t he cent ral 10 degrees
of vision. (From Hort on JC, Hoyt WF. The represent at ion of t he visual f ield in
human st riat e cort ex. A revision of t he classic Holme's map. Arch O phthal mol
1991; 109: 816. Copyright . )
I n addit ion t o t he cent ral ret inal art ery, t he opht halmic art ery gives off dural
branches (ant erior f alcine and recurrent meningeal art eries), orbit al branches,
and several post erior ciliary art eries. The post erior ciliary art eries f orm a rich
anast omot ic circle on t he post erior aspect of t he globe near t he opt ic nerve and
supply some sect ors of t he opt ic disc, t he out er layers of t he ret ina (including
phot orecept ors), and t he choroid. I n about half of t he populat ion, t he region of
t he macula and papillomacular bundle receives it s vascular supply f rom one or
more cilioret inal art eries, w hich are branches of t he post erior ciliary art eries
(Fig. 7-1). This explains t he sparing of cent ral vision t hat occurs in some
individuals despit e cent ral ret inal art ery occlusion (CRAO ) w it h global ret inal
ischemia. Unlike ischemia in t he t errit ory of t he cent ral ret inal art ery, ischemia in
t he t errit ory of t he post erior ciliary art eries is seldom relat ed t o emboli but is
usually caused by eit her at herosclerot ic disease or hypot ension (nonart erit ic
ant erior ischemic opt ic neuropat hy [ AI O N] ) or a vasculit is (art erit ic ischemic
opt ic neuropat hy [ I O N] due t o t emporal or giant cell art erit is). How ever, f ield
def ect s result ing f rom lesions in t he t errit ory of t he post erior ciliary art eries are
also alt it udinal, and t he diff erent iat ion of lesions in eit her t errit ory rest s on t he
opht halmoscopic f indings. Edema of t he ret ina is obvious in t he acut e st ages of
ret inal inf arct ion ow ing t o CRAO , but t he ret ina may appear normal or show
axonal sw ellings (cot t on w ool spot s) in a segment al dist ribut ion in t he presence
of ischemia in t he t errit ory of t he post erior ciliary art eries.
The dist al part of t he opt ic nerve (near t he globe) is supplied by small branches
of t he opht halmic art ery and, as it approaches t he chiasm, by t hin vessels f rom
t he carot id and ant erior cerebral art eries. Similarly, t hin vessels originat ing in
t he region of t he ant erior communicat ing art ery supply t he dorsal aspect of t he
chiasm, w hereas t he inf erior aspect receives art erioles f rom t he carot id,
post erior communicat ing, and post erior cerebral art eries. The lat t er t w o vessels
also supply t he opt ic t ract , w hich in addit ion is f ed by t he ant erior choroidal
art ery, a branch of t he int ernal carot id. The lat eral geniculat e body receives a
dual supply, f rom t he ant erior choroidal art ery lat erally and f rom t he lat eral
post erior choroidal art ery medially. The upper (pariet al) port ion of t he opt ic
radiat ions is supplied by branches of t he middle cerebral art ery, w hereas t he
low er part receives branches f rom t he post erior cerebral art ery. The post erior
cerebral art ery, part icularly it s calcarine branch running in t he calcarine f issure,
supplies t he primary visual cort ex. Anast omot ic branches f rom t he middle
cerebral art ery (generally t he angular or post erior t emporal art eries) also play
an import ant role in t he vascular supply of t he occipit al pole, in w hich t he
macular region is represent ed.
Localization of Lesions in the Optic Pathw ays
The long course of t he visual pat hw ays along t he base of t he brain and t heir
relat ive simplicit y render t hem a very usef ul t ool in lesion localizat ion. Various
t echniques of neuro-opht halmologic t est ing are review ed by G laser [47] . Det ailed
quant it at ive t est ing allow s t he f ollow ing:
1. The det ect ion of subt le def icit s t hat may escape det ect ion by bedside
maneuvers
2. Bet t er def init ion of abnormalit ies, such as t he exact shape of a f ield def ect ,
w hich may be import ant in lesion localizat ion
3. The quant if icat ion of t he ext ent and int ensit y of a def icit , w hich are very
usef ul dat a w hen judging t he evolut ion of a disease process
How ever, det ailed t est ing requires equipment t hat is unavailable at t he bedside
and a degree of act ive cooperat ion t hat is of t en lacking in pat ient s w it h brain
disorders.
Lesions in t he visual syst em may cause impaired visual percept ion or object ive
def icit s. I mpaired visual percept ion may include (a) poor discriminat ion of f ine
det ails of high cont rast (visual acuit y), w hich result s in diff icult y w it h t asks such
as reading a print ed page; (b) impaired color recognit ion; (c) impaired
discriminat ion of object s t hat have lit t le cont rast w it h t he background (cont rast
discriminat ion); and (d) visual f ield def ect s, t he pat t ern of w hich is of t en t he
most helpf ul clue t o lesion localizat ion. O bject ively, ret inal changes caused by
ret inal or more proximal lesions can be seen w it h t he opht halmoscope, and an
impaired pupillary response
t o light may bet ray a lesion in t he aff erent arc of t his ref lex.
Changes in Visual Perception

Visual Acuity
Vi sual acui ty, t he capacit y f or visual discriminat ion of f ine det ails of high
cont rast , such as small black let t ers on a w hit e page, ref lect s t he f unct ion of t he
macular region. A subnormal value of acuit y indicat es a f ault in t he visual syst em
(e. g. , opt ical f ault s, ret inal lesions, or visual pat hw ay lesions), f ault y f oveat ion
(i. e. , an eye mot ilit y def ect ), or poor cooperat ion, singly or in combinat ion [41] .
I t remains unimpaired by unilat eral lesions dorsal t o t he opt ic chiasm [41] . I n
pract ice, visual acuit y is most of t en impaired by changes in t he shape of t he
globe and in t he ref ract ory charact erist ics of t he t ransparent media of t he eye.
Pat ient s w it h t hese ref ract ory def ect s regain a much bet t er acuit y w hen looking
t hrough a pinhole (pinhole t est ) because t his maneuver rest rict s vision t o t he
cent ral beam of light , w hich is undist urbed by abnormal ocular dist ances or
t ransparent media. At t he bedside, visual acuit y can be t est ed by asking t he
pat ient t o read a “near card” w it h t he Snellen opt ot ypes print ed on it . The card
should be w ell-illuminat ed and held 14 inches in f ront of t he pat ient 's eyes.
O nce ref ract ory def ect s have been excluded, it can be accept ed t hat changes in
visual acuit y are secondary t o lesions in t he macular region or it s project ion. The
macula is t he only part of t he ret ina t hat has high visual acuit y. Virt ually, all
compressive and most noncompressive lesions of t he opti c nerve cause a drop in
visual acuit y, of t en even bef ore a f ield def ect can be det ect ed. Medi al chi asmal
l esi ons behave in a similar manner. Lat eral chiasmat ic lesions t end t o impair
visual acuit y in t he ipsilat eral eye only. From t hese f indings and f rom t he sparing
of visual acuit y t hat occurs w it h ret rochiasmat ic lesions, Frisen post ulat ed t hat
acuit y w ill remain normal if eit her t he crossing or t he noncrossing set of nerve
f ibers f rom t he f ovea remains int act [38] . Bot h set s of f ibers are of t en aff ect ed
w it h medial chiasmat ic lesions. Unilat eral lesions of t he opti c tract, l ateral
geni cul ate body, vi sual radi ati ons, or stri ate cortex do not impair visual acuit y.
When t he ret rochiasmal pat hw ays are aff ect ed bilat erally, visual acuit y f ails t o
t he same degree in bot h eyes.
Contrast Sensitivity
Contrast sensi ti vi ty testi ng may det ect more subt le impairment s in t he f unct ion of
t he macula, opt ic nerve, and chiasm t han visual acuit y t est ing [17, 96] . For
inst ance, visual acuit y may become normal af t er an acut e O N, yet t he pat ient
may complain of “dimness” or “f uzzy vision” in t hat eye. This pat ient 's abilit y t o
perceive a series of bars t hat have very lit t le cont rast f rom t he background w ill
probably be abnormal. I mpaired cont rast sensit ivit y probably has localizing
signif icance t hat is similar t o t hat of impaired visual acuit y, but it has been
st udied less t horoughly.
Perception of Color
Col or percepti on is of t en degraded in areas of t he visual f ields t hat correspond
t o a part ial f ield def ect . For inst ance, a scot oma f or blue or f or red may be
demonst rat ed w hen vision f or w hit e t arget s is st ill good. I n conf ront at ion t est ing
of t he visual f ields, one of t he most usef ul t echniques is t o ask t he pat ient w hich
one of t w o ident ically bright red object s is more red, because a desat urat ion f or
red is of t en caused by lesions of t he visual pat hw ays. A color sample t hat
appears red t o t he healt hy eye appears more yellow ish t o t he def ect ive eye and
passes f rom orange t o yellow t o colorless as disease severit y increases.
I mpairment of color vision may also be det ect ed by asking t he pat ient t o read
numbers composed of an assembly of dot s of diff erent colors embedded in a
background of diff erent ly colored dot s (I shihara or Hardy-Rand-Rit t ler
pseudoisochromat ic color plat es). Color-blind pat ient s cannot perf orm t his t ask,
w hich mainly ref lect s macular f unct ion. Because opt ic nerve and chiasmat ic
lesions of t en aff ect t he macular f ibers, monocular reading of t he I shihara or
similar plat es may be def ect ive on t he side of t he lesion. How ever, I shihara
plat es generally have poor sensit ivit y f or acquired dyschromat opsia. I t should
also be not ed t hat t he int erpret at ion of pseudoisochromat ic color plat es requires
t hat t he pat ient is able t o “put t he dot s t oget her” t o make a visual w hole.
Theref ore, pat ient s w it h simult anagnosia (see Chapt er 20) due t o bilat eral
occipit opariet al damage (e. g. , in t he “post erior” f orm of Alzheimer's disease)
may have diff icult y in ident if ying t he images on t he plat es despit e adequat e
visual acuit y and t he abilit y t o name all t he colors in t he plat es correct ly [16] .
Color vision loss usually parallels visual acuit y loss (e. g. , in I O N), but in O N
color vision loss may be much w orse. I n O N, chromat ic sensit ivit y is more
severely impaired t han luminance sensit ivit y [122a. Anot her except ion t o t he
general rule of color vision f ailure paralleling visual acuit y impairment is t hat
color vision does not depend equally on perf ect f oveat ion and a w ell-f ocused
ret inal image, so t hat pat ient s w it h nyst agmus and anisomet ropia usually have
normal color vision
unless acuit y is severely impaired. Acuit y may also be normal w it h acquired

achromat opsia due t o cerebral cort ical lesions [31, 142] .
Congenit al color vision def ect s are much more common in men t han w omen, w it h
def icit s mainly of red and green hues. Acquired color vision def ect s clust er
primarily in t he blue-purple or blue-green hues [122] . Theref ore, bluish-purple
object s may have superior sensit ivit y over red t arget s in assessing acquired
dyschromat opsia. I n general, pat ient s w it h primary opt ic nerve disease
f requent ly show a t endency f or hue discriminat ion diff icult ies bet w een reds and
greens, w hereas pat ient s w it h primary ret inochoroidal disorders more f requent ly
show evidence of hue discriminat ion diff icult ies bet w een blues and yellow s
(Köl l ner's rul e) [62] . How ever, Köllner's rule has numerous except ions (e. g. ,
primary open angle glaucoma is an opt ic nerve disease charact erized by blue-
yellow def icit s).
Anot her w ay of revealing impaired color processing involves t he f l i ght-of -col ors
phenomenon, w hich consist s of a succession of color impressions t hat normally
f ollow s shining a bright light int o t he eye. This phenomenon is absent or reduced
in durat ion w it h acquired dyschromat opsia [38] .
I mpairment of color percept ion also occurs w it h lesions in t he post erior visual
pat hw ays. A visual f ield def ect f or red may bet ray t he presence of a lesion w hen
t he f ields f or w hit e st imuli are f ull. Pat ient s w it h bilat eral lesions of t he
inf eromedial occipit al region of t en have color blindness w it h normal visual acuit y
[ 31, 142] .
Visual Fields
The shape and dist ribut ion of vi sual f i el d loss closely ref lect s t he sit e of t he
lesion (Fig. 7-11). Theref ore, caref ul plot t ing of t he visual f ields is most helpf ul
in t he localizat ion of lesions of t he visual pat hw ays w hen examining a
cooperat ive pat ient [41] . I n pat ient s w it h a markedly reduced at t ent ion span or
ot her dist urbances in alert ness or ment at ion, t he gross ext ent of t he visual f ields
can be est imat ed f rom t he pat ient 's response t o moving object s in diff erent
quadrant s. A moving object st rongly induces t he pat ient t o look at it . How ever,
small f ield def ect s are missed w it h conf ront at ion t echniques [165] . I n
cooperat ive pat ient s, visual f ield t est ing w it h t he t angent (Bjerrum) screen or
st at ic or kinet ic perimet ry provides a det ailed map of t he visual f ields. Test ing of
t he cent ral 20 t o 30 degrees of vision is most import ant because very f ew
disease processes aff ect t he peripheral f ields alone; except ions t o t his are t he
t apet oret inal degenerat ions and ret inal det achment (bot h diagnosed by
opht halmoscopic exam) and ant erior visual cort ex lesions [41] .
Adequat e visual f ield t est ing requires pat ient cooperat ion and a skilled examiner.
Shadow ing f acial cont ours (e. g. , t he eyebrow s and nose), pt osis, disorders of
eye mot ilit y, blinks, pupillary size, eyelashes, and spect acle rims must all be
t aken int o account w hen int erpret ing t he visual f ields [41] . Amet ropia,
presbyopia, or bot h may aff ect t he f ields. For example, uncorrect ed ast igmat ism
may cause an upper t emporal depression suggest ing a chiasmat ic lesion;
how ever, unlike a t rue chiasmat ic def ect , t his def ect does not respect t he
vert ical meridian and spares cent ral f ixat ion [41] . Spherical amet ropia may cause
generalized f ield depression and occasionally an upper t emporal depression,
w hich may run under t he blind spot (bari ng of the bl i nd spot) due t o local
amet ropia or local deviat ion f rom t he normal ret inal curvat ure [41] .
By convent ion, in represent ing t he visual f ields, t he f ield f or t he lef t eye is
represent ed t o t he lef t of t he f ield f or t he right eye (Fig. 7-11). Theref ore, t he
nasal reti na of t he lef t eye “sees” t he temporal f i el d of t he lef t eye. This
t erminology explains w hy a chiasmat ic lesion t hat dest roys t he nasal f i bers f rom
bot h ret inas causes a bi temporal hemianopia. Similarly, a macular lesion yields a
cent ral def ect , w hereas a lesion in t he nasosuperior ret ina of t he right eye
result s in a f ield def ect in t he t emporoinf erior port ion of t he visual f ield
corresponding t o t he right eye.
Any localized area of poor vision surrounded by areas of normal vision is t ermed
a scotoma. The blind spot , t he project ion of t he opt ic nerve in t he visual f ield, is
a physiologic scot oma t hat cannot be perceived because it lacks represent at ion
in t he brain. Angioscot omat a, t he shadow images of t he superf icial ret inal
vessels on t he underlying ret ina, is anot her t ype of physiologic scot oma t hat may
be not ed under cert ain circumst ances. Absolut e def ect s involving t he out er limit s
of t he visual f ield are called contracti ons, w hereas depressi ons are smoot hly
t apering but not absolut e def icit s in t he f ield [41] .
Types of Visual Field Defects

A central def ect occupies t he posit ion of t he macula (Fig. 7-2). A cecocentral
def ect aff ect s t he area of t he macula and of t he papillomacular bundle. Nerve
f i ber bundl e def ects are f ield abnormalit ies in w hich at least part of t he border
coincides w it h t he course of t he ret inal nerve f iber layer [41] . Peripheral nerve
f i ber bundl e def ects in t he nasal f ield t end t o have an arcuate shape w hen t hey
are secondary t o ret inal or opt ic nerve disease, as t hey of t en are. The f ield
def ect t akes t his arcuat e shape because of t he disposit ion of t he f iber layer in
t he ret ina and in t he opt ic nerve (Fig. 7-2).
Arcuat e f ield def ect s may occur w it h glaucoma, AI O N, drusen of t he disc, and
congenit al opt ic pit s. Small deep ret inal lesions result in a discret e def ect
localized t o t he point of t he lesion, because t he f iber layer remains unalt ered.
Larger lesions aff ect t he superf icial f iber layer and t heref ore give rise t o a f an-
shaped arcuat e def ect , w it h it s t ip point ing t o t he lesion and it s base f anning
peripherally and t ow ard t he nasal horizont al meridian. Nerve f iber bundle def ect s
occur most commonly w it h lesions in t he opt ic nerve head, w here t he t ip of t he
def ect reaches t o t he blind spot (Fig. 7-2), but may also occur w it h branch
ret inal art ery or vein occlusion and w it h juxt apapillary inf lammat ion. Def ect s in
t he temporal f ield lat eral t o t he blind spot have t he appearance of a sector
rat her t han an arcuat e shape. Visual def ect s in t he t emporal f ield do not
“respect ” t he horizont al meridian because neit her t he blood supply nor t he f ibers
of t he nasal ret ina are arranged along a horizont al raphe (as opposed t o
t emporal ret inal f ibers). The st raight course of t he ret inal f ibers of t he nasal
ret ina t ow ard t he nerve head explains t his sect or conf igurat ion (Fig. 7-1).
FI G URE 7-11 Visual f ield def ect s w it h chiasmat ic and ret rochiasmat ic
lesions. Visual f ields f rom bot h eyes are usually abnormal. There is great er
similarit y bet w een t he f ield def ect s in each eye (congruit y) w it h more
post eriorly locat ed lesions.
Enl argement of the bl i nd spot is of t en not ed w it h any process causing disc

sw elling (e. g. , increased int racranial pressure); how ever, any peripapillary
ret inal disorder (e. g. , t he peripapillary conus or crescent seen w it h aging,
myopia, or glaucoma and congenit al opt ic nerve pit ) may also enlarge t he blind
spot . These abnormalit ies are usually observed on opht halmoscopic examinat ion.
O ccasionally a f ield def ect has t he appearance of a ri ng, w it h preserved vision

cent ral and peripheral t o t he scot oma. Usually t he cent er coincides w it h t he
f ovea. Annular or ring scot omas may occur w it h ret inopat hies or opt ic
neuropat hies. Ret init is pigment osa of t en result s in a large midperipheral ring
scot oma. Cancer-associat ed ret inopat hy (CAR) syndrome may also cause a ring
scot oma, of t en associat ed w it h f unduscopic evidence of art eriolar narrow ing and
opt ic at rophy [28] . Ring scot omas of small diamet er may occur w it h macular
lesions, especially associat ed w it h a “bull's-eye” appearance on opht halmoscopy
(e. g. , chloroquine ret inopat hy [63] ) or w it h t he ret inal disorder f undus
f lavimaculat us [141] . Annular or ring scot omas may also occur w it h ret init is,
choroidit is, ret inal migraine, and myopia. Paracent ral and arcuat e scot omas are
charact erist ic of glaucoma; f usion of superior and inf erior arcuat e def ect s gives
rise t o ring scot omat a. These ring-shaped def ect s have a charact erist ic
hori zontal or nasal step ( Fig. 7-2), w hich dist inguishes t hem f rom lesions locat ed
more dist ally in t he visual pat hw ays. Physiologic ring scot omas may be caused
by correct ive lenses, t he prismat ic eff ect s of st rongly curved correct ing lenses,
and t he shallow ring scot oma surrounding t he blind spot [41] .
When only cent ral vision is int act , t he visual f ield is said t o be narrow ed, and t he
pat ient has f unnel vi si on, not t o be conf used w it h tunnel vi si on, a f ield def ect
charact erist ic of hyst eria or malingering. This lat t er f ield def ect can easily be
mapped ont o a t angent screen by plot t ing t he f ields w it h t he pat ient seat ed 1
and 2 m f rom t he screen (t he t arget size is doubled at 2 m) or can be det ect ed
w it h conf ront at ion met hods. Logically, w it h an organic f ield def ect , t he f ield
project ed at 2 m is larger t han t he f ield plot t ed at 1 m (f unnel vision). I dent ical
f ields are obt ained w hen t he const rict ion of t he f ield is not due t o a lesion of t he
visual syst em. Const rict ed visual f ields w it h ret ained acuit y may be due t o
glaucoma, ret init is pigment osa, CAR, hyaline bodies of t he disc, post papilledema
opt ic at rophy, bilat eral occipit al inf arct s w it h macular sparing, and f eigned visual
loss.
Hemi anopi a i s a f ield def ect t hat encompasses roughly half of t he f ield, w it h a
f airly sharp cut off at t he vert ical or horizont al meridian (Fig. 7-11) [159] . Vert ical
hemianopia can be nasal or t emporal. Horizont al or “alt it udinal” hemianopia can
be superior or inf erior. When only one-f ourt h of t he f ield is aff ect ed, t he result ing
def icit is called quadrantanopi a.
Bilat eral f ield def ect s are said t o be homonymous w hen t hey are similarly
locat ed in bot h visual f ields. They are congruous w hen t here is a point -t o-point
correspondence of t he def ect in eit her f ield; ot herw ise t hey are called
i ncongruous ( Fig. 7-11).
Uni l ateral vi sual i nattenti on ref ers t o t he phenomenon f ound in some pat ient s
w it h pariet o-occipit al lesions. No f ield def ect is f ound on unilat eral t est ing, but
w hen st imuli are placed on bot h right and lef t hemif ields, t he pat ient appears not
t o see t he object on t he f ield opposit e t o t he lesion. Unilat eral visual inat t ent ion
is of t en seen w it h incomplet e homonymous def ect s and in t he process of
recovery of a dense f ield def ect , part icularly at t he margins of t he def ect .
Dissociat ion of t he percept ion of ki neti c and stati c st imuli (Riddoch's
phenomenon) occasionally occurs w it h occipit al lesions, and less of t en w it h
lesions anyw here in t he opt ic pat hw ays (e. g. , opt ic t ract and opt ic chiasm
lesions). I n t his case, t he pat ient can st ill appreciat e moving object s w it hin a
dense f ield def ect f or st at ic st imuli [11] . I n some cases, nonst riat ed project ions
might mediat e visual f unct ion in t he absence of st riat e cort ex (e. g. , t hrough
superior colliculus-pulvinar-prest riat e cort ex pat hs).
Localization of Visual Field Defects

Most import ant f or lesion localizat ion, is t o not e w het her t he f ield def ect is
monocul ar, in w hich case t he lesion usually aff ect s t he ret ina or t he opt ic nerve,
or bi nocul ar, in w hich case t he lesion is localized t o or beyond t he opt ic chiasm
(Figs. 7-2 and 7-11). O bviously, mult iple lesions in t he visual pat hw ays, w hich
occur f requent ly w it h mult iple sclerosis (MS) and ot her condit ions, may result in
bilat eral loss even w hen t he ant erior opt ic pat hw ays are involved. The pat t ern of
t he visual f ield loss can seldom diff erent iat e ret inal f rom opt ic nerve disease.
How ever, ret inal involvement generally accompanies obvious opht halmoscopic
abnormalit ies. Also, most opt ic neuropat hies involve visual acuit y; spared acuit y
should raise t he suspicion of preret inal, ret inal, or ret rochiasmal disease [41] .
Monocul ar vi sual f i el d def ects are almost alw ays due t o disease of t he choroid,
ret inal pigment epit helium, ret ina, opt ic disc, or opt ic nerve. Lesions aff ect ing
t he ret ina, nerve f iber layer, or opt ic nerve produce visual f ield def ect s in t he
ipsilat eral eye, w hich correspond in posit ion, shape, ext ent , and int ensit y t o t he
lesion. Almost all ret inal lesions result ing in visual f ield loss are visible
opht halmoscopically. Caref ul at t ent ion should be direct ed t o t he ret ina and
ret inal nerve f iber layer corresponding t o t he visual f ield def ect . Pat ient s w it h
macular disease may also complain of met amorphopsia, micropsia, and posit ive
phot opsias (e. g. , f lashing light s), w hich are unusual in pat ient s w it h opt ic
neuropat hies.
I n assessing opt ic nerve–relat ed visual f ield def ect s, several anat omic point s are
w ort h remembering:
1. Fibers f rom peripheral ganglion cells occupy a more peripheral posit ion of
t he opt ic disc, w hereas f ibers f rom ganglion cells locat ed closer t o t he disc
occupy a more cent ral posit ion.
2. Peripheral f ibers course peripherally t hrough t he ent ire ext ent of opt ic nerve.
3. The papillomacular bundle occupies a large sect or-shaped region of t he
t emporal disc. This bundle of f ibers moves cent rally in t he more dist al
(post erior) port ions of t he orbit al opt ic nerve.
4. All ret inal f ibers ret ain t heir relat ive posit ions t hroughout visual pat hw ays
except in t he opt ic t ract and at t he lat eral geniculat e nucleus w here t here is
a rot at ion of 90 degrees t hat becomes “st raight ened out ” in t he opt ic
radiat ions.
Central visual f ield def ect s (unilat eral or bilat eral) are t he result of damage t o
t he papillomacular bundle or opt ic nerve. Any visual f ield def ect produced by a
ret inal lesion may be produced by a lesion of t he opt ic nerve [119] and virt ually
any et iology may be responsible (e. g. , glaucomat ous, degenerat ive, ischemic,
t raumat ic, inf lammat ory, inf ilt rat ive, compressive, or vascular opt ic neuropat hy).
For example, unilat eral cent ral scot omas are of t en seen w it h O N, compressive
opt ic neuropat hies, or early macular disease. Bilat eral cent ral or cecocent ral
scot omas usually indicat e heredit ary (e. g. , Leber's heredit ary opt ic neuropat hy)
or t oxic-nut rit ional opt ic neuropat hies, but may also be seen w it h bilat eral
macular lesions, bilat eral compressive lesions aff ect ing t he opt ic nerves, or even
bilat eral lesions aff ect ing t he occipit al poles. The clinical f eat ures and et iologies
of bilat eral superior and inf erior alt it udinal def ect s and bilat eral cent ral or
cecocent ral scot omas are not ed in Table 7-1.
Alt hough monocular visual f ield def ect s are usually due t o ret inal or opt ic nerve
disease, in t he early st ages of a chiasmat ic lesion, t he loss may be rest rict ed t o
t he t emporal port ion of t he
f ield corresponding t o t he ipsilat eral eye [69] . This monocular (of t en

scot omat ous) t emporal hemianopia (juncti onal scotoma of Traquai r, Fig. 7-12) is
at t ribut ed t o t he involvement of t he ipsilat eral opt ic nerve close enough t o t he
chiasm t o impair conduct ion select ively in ipsilat eral crossing f ibers but t oo
ant erior t o aff ect nasal ret inal f ibers crossing f rom t he f ellow eye (i. e. , nasal
compression of t he dist al int racranial opt ic nerve ipsilat eral t o t he def ect ) [69] .
Also, lesions locat ed in t he most ant erior ext ent of t he calcarine cort ex cause a
crescent -shaped def ect rest rict ed t o t he t emporal f ield of t he cont ralat eral eye
f rom 60 t o 90 degrees (monocul ar temporal crescent or “hal f -moon syndrome”)
[ 25, 102] . This is t he only ret rochiasmat ic lesion t hat may cause a st rict ly
unilat eral visual f ield def ect (Fig. 7-11). Similarly, an occipit al lesion t hat spares
t he f oremost part of t he calcarine cort ex result s in a homonymous hemianopia
t hat spares t he unpaired t emporal crescent (Fig. 7-11).
TABLE 7-1 Clinical Features and Etiologies of

Bilateral Superior or Inferior Altitudinal Defects and
Bilateral Central or Cecocentral Scotomas
Bilateral superior or inferior (altitudinal hemianopia)
Mostly caused by bilateral optic nerve or retinal

disease
Rarely, a large prechiasmal lesion compresses both
nerves inferiorly to cause bilateral superior
hemianopia. Compression of nerves from below may
also elevate them against the dural shelves
extending out from the intracranial end of the optic
canals and cause bilateral inferior altitudinal defects
Bilateral symmetric damage to postchiasmal
pathways may cause bilateral altitudinal defects.
Bilateral lesions of the medial aspect of the lateral
geniculate body may cause bilateral inferior
hemianopias
Bilateral occipital lesions may cause bilateral
inferior, and less often, superior hemianopias
Bilateral “checker board” altitudinal hemianopia—
superior defect in one eye and inferior defect in the
other eye
Bilateral optic neuropathies
Visual field defects may cause binocular diplopia
because of vertical hemifield slide—preexisting
minor phoria becomes a tropia because of vertical or
horizontal separation or overlap of two
nonoverlapping hemifields; this phenomena may also
occur with broad arcuate defects
Bilateral cecocentral or central scotomas

May be bilateral optic neuropathy of any cause (e.g.,
compressive) but more common etiologies include the
following:
Toxic or nutritional amblyopia

Bilateral demyelinating optic neuritis
Syphilis
Leber's hereditary optic neuropathy
Bilateral macular disease
Bilateral macular involving occipital lesions
Adapted from Lee AG, Brazis PW. Clinical pathways in
neuro-ophthalmology. An evidence-based approach.
New York: Thieme Medical Publishers, 2003, with
permission of authors.
FI G URE 7-12 Junct ional scot oma of Traquair.
Monocul ar al ti tudi nal def ect s (Fig. 7-2), w hich are of t en accompanied by
macular sparing, are charact erist ic of disease in t he dist ribut ion of t he cent ral
ret inal art ery. Cent ral vision may be spared because t he blood supply f or t he
macula of t en derives f rom t he cilioret inal art eries (Fig. 7-1). AI O N (inf arct ion
involving t he ant erior port ion of t he opt ic nerve), due t o ischemia involving t he
post erior ciliary art eries, is anot her common cause of an alt it udinal (usually
inf erior) def ect (see subsequent t ext ). O t her causes of a monocular alt it udinal
def ect include choroidit is, choroidal coloboma, ret inal det achment , glaucoma,
opt ic nerve hypoplasia, chronic at rophic papilledema, drusen, O N, opt ic nerve
t rauma, and masses aff ect ing t he opt ic nerve or chiasm. Bi l ateral al ti tudi nal
def ect s may result f rom bilat eral lesions, of t en ischemic, of t he ret inas or opt ic
nerves, but bilat eral occipit al lesions, especially t rauma or inf arct ion, may also
be responsible f or t his t ype of def ect (Table 7-1) [61, 99] . Rarely, a large
prechiasmal lesion compresses bot h nerves inf eriorly t o cause bilat eral superior
alt it udinal def ect s. The compression of nerves f rom below may also elevat e t hem
against t he dural shelves ext ending out f rom t he int racranial end of t he opt ic
canals and cause bilat eral inf erior alt it udinal def ect s. Bilat eral lesions of medial
aspect of t he lat eral geniculat e body may cause bilat eral inf erior alt it udinal
def ect s. I t is import ant t o emphasize t hat t he nerve f iber layer of t he ret ina
respect s t he horizont al meridian only in t he nasal f ield, not in t he t emporal f ield;
t heref ore, incomplet e alt it udinal f ield def ect s are more common w it h ret inal
lesions. Because of t he anast omot ic blood supply of t he occipit al pole, only
alt it udinal def ect s due t o occipit al inf arct s spare macular vision [61, 99] .
Diagnosis of ret inal branch art ery occlusion or AI O N is aided by t he presence of
a unilat eral alt it udinal def ect along w it h ipsilat eral f unduscopic changes and, in
most bilat eral cases, by sequent ial t emporal development ; bilat eral occipit al
inf arct s are charact erized by t he sudden, simult aneous onset of alt it udinal visual
f ield def ect s w it h an absence of ret inal or
opt ic nerve abnormalit y or abnormalit ies of t he pupillary response [99] .

Bi l ateral ri ng def ect s may be t he consequence of ret inal disease, but bilat eral
occipit al involvement can cause a similar f ield def ect . I n t he case of occipit al
lesions, how ever, a vert ical st ep can be regularly ident if ied bet w een t he t w o
halves of t he ring (Fig. 7-11).
Bi temporal f i el d def ects [ 126] are most of t en due t o a compressive mass lesion
aff ect ing t he opt ic chiasm, such as pit uit ary t umors. Rarely, processes t hat
cause rapidly developing hydrocephalus in children may result in bit emporal
def ect s, perhaps t hrough dilat ion of t he opt ic recess of t he t hird vent ricle. True
pure complet e bit emporal hemianopias are rare because it is diff icult f or any
pat hogenet ic mechanism, except t rauma, t o aff ect crossing f ibers only.
Bit emporal hemianopsia may be peripheral, paracent ral, or cent ral. The visual
f ield def ect may “split ” or “spare” t he macular cent ral f ield. Cert ain anat omical
relat ionships are import ant in evaluat ing chiasmal visual f ield def ect s:
1. The rat io of crossed t o uncrossed f ibers in t he chiasm is 53: 47.

2. Uncrossed f ibers, bot h dorsal and vent ral, maint ain t heir relat ive posit ion at
t he lat eral aspect s of t he chiasm and pass direct ly int o t he ipsilat eral opt ic
t ract .
3. Dorsal ext ramacular crossing f ibers f rom each eye decussat e post eriorly in
t he chiasm and t hen direct ly ent er t he dorsomedial aspect of cont ralat eral
opt ic t ract .
4. Macular f ibers t hat cross do so in t he cent ral and post erior port ions of
chiasm.
5. Some inf eronasal ret ina f ibers, primarily peripheral f ibers, loop in Wilbrand's
loop (alt hough t he anat omic exist ence of t his st ruct ure has been quest ioned).
Early chiasmal compression w it h pit uit ary t umors aff ect ing crossing f ibers in
isolat ion usually result s in relat ive rat her t han absolut e def ect s limit ed t o t he
cent ral part s of t he upper t emporal quadrant s. Wit h increasing t umor grow t h, t he
cont act area w it h t he chiasm increases in size so t hat noncrossing f ibers are
alw ays aff ect ed and acuit y is impaired. Theref ore, complet e bilat eral hemianopia
almost never occurs in isolat ion and is usually combined w it h binasal depression
and subnormal acuit y [41] . Alt hough most pat ient s w it h midchiasmal compression
demonst rat e bit emporal superior visual depression, occasional pat ient s may
demonst rat e bit emporal scot omas or, rarely, bilat eral arcuat e def ect s [47] .
Clinically, t hree chiasmat ic syndromes may be recognized (Fig. 7-13) [119] .
1. The anteri or chi asm or juncti onal syndrome ( di f f erent f rom t he junct ional
syndrome of Traquair, above), in w hich a unilat eral opt ic def ect is associat ed
w it h a superior t emporal def ect in t he ot her eye.
2. Body of the chi asm syndrome, in w hich pat ient s demonst rat e bit emporal
visual f ield def ect s. These visual f ield def ect s may be peripheral, cent ral, or
a combinat ion of bot h, w it h or w it hout “split t ing of t he macula, ” and may be
quadrant ic or hemianopic. Visual acuit y is usually normal, and t he opt ic discs
are normal or pale.
3. The posteri or chi asm syndrome, in w hich visual f ield t est ing reveals
bit emporal scot omas (t he peripheral visual f ields are int act ). Visual acuit y
and t he opt ic discs are normal.
Lesions aff ect ing t he opt ic chiasm are list ed in Tables 7-2 and 7-3. Superior
bit emporal f ield def ect s may also occur w it h ti l ted di scs, an opt ic disc anomaly
in w hich t he discs have an ellipt ical shape. This f ield anomaly diff ers f rom t hat
due t o a chiasmat ic lesion in t hat w it h t ilt ed discs, t he def ect crosses t he median
int o t he nasal f ield (i. e. , does not “respect ” t he vert ical meridian) [46, 59] .
Pseudochiasmal visual f ield def ect s (i. e. , bit emporal def ect s t hat do not respect
t he vert ical midline) may also be due t o amet ropia, ast igmat ism, colobomas,
bilat eral nasal ret inal disease (e. g. , schisis), glaucoma, and bilat eral opt ic
neuropat hies.
A central def ect in one f ield w it h a superi or t emporal def ect in t he opposit e f ield
point s t o t he involvement of t he ant erior angle of t he chiasm, w it h damage of t he
ipsilat eral opt ic nerve and of t he loop made by t he f ibers f rom t he inf eronasal
ret ina of t he ot her eye (Wilbrand's knee) (Figs. 7-7 and 7-13A). Because of it s
localizing implicat ions, t his t ype of visual f ield def ect has been t ermed juncti onal
scotoma (diff erent f rom t he junct ional syndrome of Traquair, as explained in
preceding t ext ) [169] . Such junct ional scot omas st ress t he import ance of
met iculous t est ing of t he visual f ields in t he “normal” eye in pat ient s w it h
apparent ly unilat eral visual impairment . As not ed in t he preceding t ext , t he
exist ence of Wilbrand's knee has come int o quest ion. Nevert heless, w het her
Wilbrand's knee exist s anat omically, t he localizing value of junct ional visual f ield
loss t o t he junct ion of t he opt ic nerve and chiasm remains undiminished because
chiasmal compression alone may result in t he cont ralat eral superot emporal visual
f ield def ect (junct ional scot oma) [84] .
FI G URE 7-13 Visual f ield def ect s w it h chiasm lesions: A: Ant erior chiasm or
junct ional syndrome. B: Body of chiasm syndrome. C: Post erior chiasm
syndrome.
TABLE 7-2 Compressive Chiasmal Syndromes
Most Common
Chiasmal glioma
Craniopharyngioma
Dysgerminoma
Meningioma
Optic chiasm diastasis from pituitary tumor
Pituitary apoplexy
Pituitary tumor (especially pituitary adenoma)
Suprasellar aneurysm
Less Common
Abscess
Anaplastic astrocytoma
Arachnoid cyst
Aspergillosis
Cavernous malformation
Chiasmal hematoma (chiasmal apoplexy)
Chondroma
Chordoma
Choristomas
Colloid cyst of the third ventricle
Dermoid
Dolichoectatic internal carotid arteries
Ependymoma
Epidermoid
Esthesioneuroblastoma
Extramedullary hematopoiesis
Fibrous dysplasia
Gangliocytoma
Ganglioglioma
Giant aneurysm of the right internal carotid artery
Giant cell tumor of bone
Glioma
Granular cell myoblastoma
Hemangioblastoma
Hemangioma
Hemangiopericytoma
Histiocytosis X
Hydrocephalus and distention of the third ventricle
Langerhans cell histiocytoma
Leukemia and lymphoma
Lipoma
Lymphocytic hypophysitis
Lymphohistiocytosis
Melanoma
Meningeal carcinomatosis
Metastatic disease to brain or pituitary gland
Mucocele or mucopyocele
Intrasellar
Sphenoid sinus
Multiple myeloma
Nasopharyngeal cancer
Neurofibroma
Non-neoplastic pituitary gland enlargement
Paraganglioma
Plasmacytoma
Pneumatocele
Rathke cleft cyst
Rhabdomyosarcoma
Sarcoid granuloma
Sarcoma
Schwannoma
Septum pellucidum cyst
Sinus tumors
Syphilitic granuloma
Teratoma
Tuberculomas
Vascular malformation
Venous aneurysm arising from carotid-cavernous
sinus fistula
Venous developmental anomaly

Trobe and G laser not ed t hat junct ional visual f ield loss w as due t o a mass lesion
in 98 out of 100 cases [166] . The diff erent ial diagnosis of a junct ional syndrome
includes pit uit ary t umors, suprasellar meningiomas, supraclinoid aneurysms,
craniopharyngiomas, and gliomas [169] . Chiasmal neurit is, pachymeningit is, and
t rauma are rare et iologies of t he junct ional syndrome [144, 176] . Junct ional
visual f ield abnormalit ies may also occur on a f unct ional (nonorganic) basis.
Bi nasal hemi anopi as and quadrant anopias may occur, are usually asymmet ric,
and of t en do not respect t he vert ical meridian. Binasal def ect s are usually due t o
bilat eral int raocular disease of t he ret ina or opt ic nerve (e. g. , chronic
papilledema, I O N, glaucoma, opt ic nerve drusen, or ret inal disease such as
sect or ret init is pigment osa or ret inoschisis) [152] . Rarely, bilat eral compression
of t he lat eral chiasm may result in a binasal def ect [132] . Bilat eral nasal def ect
may occur w it h hydrocephalus w it h t hird vent ricle enlargement causing lat eral
displacement of opt ic nerves against t he supraclinoid port ion of t he int ernal
carot id art eries. Binasal def ect s have also been
described in pat ient s w it h primary empt y sella syndrome and w it h ot her
suprasellar lesions [24, 112] . An unusual binasal visual f ield impairment has been
not ed w it h spont aneous int racranial hypot ension f rom a dural cerebrospinal f luid
leak [71] . Some of t hese pat ient s have a binasal def ect w it h peripheral
depressions t hat are most severe in t he upper nasal quadrant s but also involving
t he low er nasal and upper t emporal quadrant s.
TABLE 7-3 Other Causes of Chiasmal Syndrome
Hydrocephalus
Cobalamin deficiency
Demyelinating disease
Empty sella syndrome (primary or secondary)
Chiasmal ischemia
Optochiasmatic arachnoiditis
Foreign body–induced granuloma (e.g., muslin)
Idiopathic
Infection
Chronic fungal infection
Cryptococcus meningitis
Cysticercosis
Encephalitis
Epstein-Barr virus infection
Meningitis
Mucormycosis
Nasopharyngeal and sinus infections
Syphilis
Tuberculosis
Inflammatory
Collagen vascular disease (e.g., systemic lupus
erythematosus)
Rheumatoid pachymeningitis
Sarcoid
Posthemorrhagic
Posttraumatic
Radiation necrosis
Shunt catheter
Toxic
Tobacco–alcohol toxicity
Ethylclorvynol (Placidyl)
Pheniprazine (Catron)
Trauma including postsurgical
Fat packing after trans-sphenoidal hypophysectomy
Tethering scar tissue causing delayed visual
deterioration after pituitary surgery
Vascular occlusion
Vasculitis
Hereditary (probably autosomal recessive) chiasmal
optic neuropathy
Nonorganic (functional)

Homonymous hemi anopi as appear w it h lesions in t he ret rochiasmat ic pat hw ays

[ 77] . Homonymous hemianopia may, t heref ore, be caused by lesions aff ect ing
t he opt ic t ract , lat eral geniculat e body, opt ic radiat ions, or occipit al lobe. Rarely,
an occipit al lesion may cause a monocular f ield def ect (see preceding t ext ).
Homonymous hemianopias aff ect ing t he t ract and lat eral geniculat e body t end t o
be i ncongruous, but t he more post eriorly t he lesion is locat ed in t he opt ic
pat hw ays, t he great er t he congruit y of t he def ect in eit her f ield. I n general,
t umors produce sloping f ield def ect s, w hereas vascular lesions produce sharp
f ield def ect s. Complet e homonymous hemianopias are nonlocalizing and may be
seen w it h any lesion of t he ret rochiasmal pat hw ay, including lesions of t he opt ic
t ract , lat eral geniculat e body, opt ic radiat ions, and st riat e cort ex.
I n t he opti c tract, macular f ibers lie dorsolat erally, peripheral f ibers f rom t he
upper ret ina are sit uat ed dorsomedially, and peripheral f ibers f rom t he low er
ret inas run vent rolat erally. Complet e unilat eral opt ic t ract lesions cause a
complet e macular split t ing homonymous hemianopia, usually w it hout impaired
visual acuit y, unless t he lesion ext ends t o involve t he opt ic chiasm or nerve
[ 155] . Part ial opt ic t ract lesions are more common t han complet e lesions and
result in an incongruous f ield def ect t hat may be scot omat ous [7, 8, 155] . The
only ot her post chiasmal locat ion f or a lesion causing a scot omat ous hemianopic
visual f ield def ect is t he occipit al lobe. O pt ic t ract lesions are of t en associat ed
w it h a relat ive aff erent pupillary def ect (RAPD) (see subsequent t ext ) in t he eye
w it h t emporal f ield loss (cont ralat eral t o t he side of t he lesion) [7, 19, 133] .
Theref ore, an aff erent pupillary def ect in t he cont ralat eral eye in a pat ient w it h
normal visual acuit y bilat erally and a complet e homonymous hemianopia are
usually indicat ive of opt ic t ract involvement [119] . Anot her abnormalit y of t he
pupil t hat may occur w it h opt ic t ract lesions is due t o concurrent t hird nerve
involvement by t he pat hologic process causing t he t ract damage. I n t hese cases,

t he pupil ipsilat eral t o t he lesion may be large and poorly react ive. Finally, many
pat ient s w it h chronic opt ic t ract lesions develop bilat eral opt ic at rophy w it h a
charact erist ic “w edge, ” “band, ” or “bow t ie” pallor in t he cont ralat eral eye
(ident ical t o t hat seen in some pat ient s w it h bit emporal visual f ield loss f rom
chiasmal lesions), and a more generalized pallor in t he ipsilat eral opt ic nerve
associat ed w it h loss of nerve f iber layer in t he superior and inf erior arcuat e
regions corresponding t o t he bulk of t emporal f ibers subserving t he nasal visual
f ields (hemianopic opt ic at rophy) [119, 155] . Hemianopic opt ic at rophy indicat es
t he involvement of t he post chiasmal, preopt ic radiat ions (i. e. , opt ic t ract or
lat eral geniculat e body damage) but has also been rarely described in congenit al
ret rogeniculat e lesions [3, 76, 119] . Et iologies of opt ic t ract lesions include
space-occupying lesions (e. g. , glioma, meningioma, craniopharyngioma,
met ast asis, pit uit ary adenoma, ect opic pinealoma, abscess, sella arachnoid
cyst ), aneurysms, art eriovenous malf ormat ions, dolichoect at ic basilar art ery,
demyelinat ing disease, and t rauma, including neurosurgical procedures (e. g. ,
t emporal lobect omy, insert ion of int ravent ricular shunt , pallidot omy f or
parkinsonism) [10, 27, 54, 56, 104, 109, 119, 155, 159, 171] . A congenit al opt ic
t ract syndrome has also been described [123] .
I n t he l ateral geni cul ate body, axons f rom ganglion cells superior t o f ovea are
locat ed medially, axons originat ing f rom ganglion cells inf erior t o f ovea are
locat ed lat erally, and macular f ibers t erminat e in a large cent ral area. As axons
leave t he lat eral geniculat e body t hey rot at e back t o t heir original posit ions so
t hat w it hin t he opt ic radiat ions and t he st riat e cort ex, f ibers t hat have synapsed
w it h axons f rom superior ret inas are locat ed in superior radiat ions and above t he
calcarine f issure in t he st riat e cort ex, w hereas f ibers t hat have synapsed w it h
axons f rom t he inf erior ret inas are locat ed in t he inf erior opt ic radiat ions and
below t he calcarine f issure. Upper f ield f ibers originat e in t he medial aspect of
lat eral geniculat e nucleus and t ravel t hrough t he pariet al lobes, w hile low er f ield
f ibers originat e f rom t he lat eral aspect of t he lat eral geniculat e body and make a
loop in t he t emporal lobe (Meyer's loop or t he Meyer-Archambault loop). Lat eral
geniculat e body lesions may also cause a complet e macular split t ing
homonymous hemianopia [57, 75, 119] . Part ial lesions result in an incongruous
homonymous f ield def ect . Hemianopic opt ic at rophy may develop and no RAPD is
usually evident .
Alt hough lesions of t he opt ic t ract or lat eral geniculat e body of t en cause
incongruous f ield def ect s, t w o relat ively specif ic pat t erns of congruous
homonymous f ield def ect s w it h abrupt ly sloping borders, associat ed w it h
sect orial opt ic at rophy, have been at t ribut ed t o f ocal lesions of t he lat eral
geniculat e body caused by inf arct ion in t he t errit ory of specif ic art eries.
O cclusion of t he ant erior choroidal art ery may cause a homonymous def ect in t he
upper and low er quadrant s w it h t he sparing of a horizont al sect or (quadrupl e
sectoranopi a) (Fig. 7-14A), w hich is essent ially diagnost ic of a lat eral geniculat e
body lesion in t he ant erior choroidal art ery dist ribut ion [40, 67, 111] . This def ect
occurs because t he lat eral geniculat e body is organized in project ion columns
orient ed vert ically t hat represent sect ors of t he f ield parallel t o t he horizont al
meridians, and t he ant erior choroidal art ery supplies t o t he hilum and
ant erolat eral part of t he nucleus. Bilat eral lat eral geniculat e lesions may
t heref ore cause bilat eral hourglass-shaped visual f ield def ect s or bilat eral
blindness [33, 118] . Q uadruple sect oranopia has also been described w it h
post erior cerebral art ery inf arct ion [89] . As not ed in t he preceding t ext , t he
lat eral geniculat e body has a dual blood supply; t heref ore, int errupt ion of t he
post erior lat eral choroidal art ery, w hich perf uses t he cent ral port ion of t he
lat eral geniculat e, causes a hori zontal homonymous sector def ect (w edge-
shaped) (Fig. 7-14B) [14, 40, 111, 124, 157, 175] . A similar sect or def ect may
occur w it h lesions aff ect ing t he opt ic radiat ions [22] or, rarely, w it h lesions
aff ect ing t he occipit al cort ex in t he region of t he calcarine f issure [55] , lesions of
t he t emporo-occipit al junct ion, pariet ot emporal lesions, or lesions in t he
dist ribut ion of t he superf icial sylvian art ery t errit ory [53] . Finally, a pat ient has
been described w it h bilat eral lat eral geniculat e lesions w it h bilat eral sect or
def ect s w it h t he preservat ion of t he visual f ields in an hourglass dist ribut ion [52] .
Pat ient s w it h lesions of t he lat eral geniculat e body may have no ot her signs or
sympt oms of neurologic involvement or may have associat ed f indings relat ed t o
t halamic or cort icospinal t ract involvement . Et iologies f or lat eral geniculat e
damage include inf arct ion, art eriovenous malf ormat ion, t rauma, t umor,
inf lammat ory disorders, demyelinat ing disease, and t oxic exposure (e. g. ,
met hanol) [13, 33, 52, 54, 67, 94, 111, 118, 124, 157] .
Superi or homonymous quadranti c def ect s (“pi e-i n-the-sky” f i el d def ects; Fig. 7-
11) may result f rom a lesion in t he temporal ( Meyer's) l oop of the opti c
radi ati ons or in t he inf erior bank of t he calcarine f issure. To cause a quadrant ic
def ect t he lesion has t o be quit e ext ensive;
small lesions result in scot omat a. I n a st udy of 30 pat ient s w it h superior
quadrant anopias, lesions w ere occipit al in 83%, t emporal in 13%, and pariet al in
3% [80] . I n t emporal lobe lesions, t he superior quadrant ic def ect is usually, but
not alw ays, incongruous and t he inf erior margins of t he def ect s may have sloping
borders and may cross beyond t he horizont al midline [119] . Also, t he ipsilat eral
nasal f ield def ect is of t en denser and comes closer t o f ixat ion t han t he def ect in
t he cont ralat eral eye. Macular vision may or may not be involved w it h t he
quadrant ic def ect [81, 113, 119] . Et iologies f or t emporal lobe dysf unct ion include
space-occupying lesions (e. g. , t umors, abscesses, hemorrhage), art eriovenous
malf ormat ions, inf arct ion, inf ect ions, congenit al malf ormat ions, demyelinat ing
disease, and t rauma (e. g. , t emporal lobect omy) [78, 81, 113, 159, 168] .
FI G URE 7-14 Visual f ield def ect s seen w it h vascular lesions of t he lat eral
geniculat e body. A: Ant erior choroidal art ery lesion. B: Lat eral choroidal
art ery lesion.
Hughes et al. st udied t he visual f ield def ect s in 32 pat ient s af t er t emporal lobe
resect ion [78] . Visual f ield def ect s w ere present in 31 of t he 32 pat ient s but
none of t he pat ient s w as aw are of t he def icit s. Point s nearest f ixat ion w ere
relat ively spared and def ect s w ere great est in t he sect or closest t o t he vert ical
meridian in t he eye ipsilat eral t o t he resect ion. I psilat eral and cont ralat eral f ield
def ect s diff ered in t opography and in dept h. This st udy, t heref ore, demonst rat ed
t hat cert ain f ibers
f rom t he ipsilat eral eye t ravel more ant eriorly and lat erally in Meyer's loop and
support s t he hypot hesis t hat visual f ield def ect s due t o ant erior ret rogeniculat e
lesions are incongruous because of anat omic diff erences in t he aff erent pat hw ay
[ 78] .
The involvement of t he opt ic radiat ions in t he dept h of t he pari etal l obe gives
rise t o an i nf eri or quadranti c def ect (“pi e-on-the-f l oor” def ect) (Fig. 7-11). Such
def ect s are usually more congruous t han t hose produced by lesions of t he
t emporal lobe, and because t he ent ire opt ic radiat ion passes t hrough t he pariet al
lobe, large lesions may produce complet e homonymous hemianopia w it h macular
split t ing [119] . Pat ient s may of t en be unaw are of t heir visual f ield def ect s [139,
173] .
I n a st udy of 41 pat ient s w it h inf erior quadrant anopias, 76% w ere due t o
occipit al lesions, 22% t o pariet al lesions, and 2% t o t emporal lesions [80] . I n
pat ient s w it h occipit al lesions, t he f ield def ect s of t en occurred in isolat ion, w hile
ot her localizing signs of pariet al involvement w ere evident in 89% of pat ient s
w it h pariet al lesions. Theref ore, alt hough visual f ield def ect s may occur in
relat ive isolat ion w it h pariet al lobe lesions, lesions in t his locat ion more of t en
bet ray t hemselves by ot her signs of neurologic dysf unct ion. Pariet al lobe lesions
may be associat ed w it h cont ralat eral somat osensory impairment , including
impaired object recognit ion, impaired posit ion sense, impaired t ouch and pain
sensat ion, and t act ile ext inct ion. Dominant pariet al lesions may cause apraxia,
f inger agnosia, acalculia, right –lef t disorient at ion, alexia, and aphasic
dist urbances, w hereas nondominant lesions may be associat ed w it h anosognosia
(denial of neurologic impairment ), aut ot opagnosia (f ailure t o recognize
hemiplegic limbs as belonging t o self ), spat ial disorient at ion, hemispat ial neglect ,
const ruct ional apraxia (abnormal draw ing and copying), and dressing apraxia
[ 105] .
Homonymous quadrant ic visual f ield def ect s may occur w it h unilat eral occi pi tal
lesions [72] . O f t en, t hese f ield def ect s have a sharp hori zontal edge t hat w ould
be diff icult t o develop w it h t umors or missile injuries because it is unlikely t hat
t hey w ould injure only one bank of t he calcarine f issure and leave t he f ellow
calcarine bank unt ouched. Theref ore, Hort on and Hoyt [72] suggest t hat a lesion
of t he extrastri ate cort ex (areas V2 and V3) w ould more likely explain t he sharp
horizont al edge of t he def ect because areas V2 and V3 are divided along t he
horizont al meridian int o separat e halves f lanking t he st riat e (V1) cort ex and,
consequent ly, t he upper and low er quadrant s in t he ext rast riat e cort ex are
physically isolat ed on opposit e sides of t he st riat e cort ex. Alt hough a lesion in
t his locat ion (e. g. , t umor) may have irregular margins, if it crosses t he
represent at ion of t he horizont al meridian in t he ext rast riat e cort ex, it produces a
quadrant ic visual f ield def ect w it h a sharp horizont al border because of t he split
layout of t he upper and low er quadrant s of V2 and V3 [72] . A congruous inf erior
quadrant anopia w it h borders aligned on bot h t he vert ical and horizont al
meridians has, how ever, also been described w it h a lesion of t he superior f ibers
of t he opt ic radiat ions near t he cont ralat eral t rigone, w here t he f ascicles of
visual axons become compact as t hey approach t he calcarine cort ex [13] .
Theref ore, a homonymous quadrant anopia respect ing t he horizont al meridian is
not a “pat hognomonic” sign of ext rast riat e cort ical disease but may occur w it h
st riat e lesions [117] . A congruous inf erior quadrant anopia w it h borders aligned
on bot h t he vert ical and horizont al meridians has also been described w it h a
lesion of t he superior f ibers of t he opt ic radiat ions near t he cont ralat eral t rigone
w here t he f ascicles of visual axons become compact as t hey approach t he
calcarine cort ex [14] .
Medial occi pi tal lesions [73, 144] cause highly congruous homonymous
hemianopias (Fig. 7-11). When bot h t he upper and t he low er calcarine cort ices
are aff ect ed, a complet e homonymous hemianopia, usually w it h macular sparing,
develops. Sparing of t he cent ral 5 degrees of vision (macular sparing) is
common w it h occipit al lesions, probably due t o a combinat ion of a large macular
represent at ion and dual blood supply [119] . The cent ral 10 t o 15 degrees of
vision f ill most of t he t ot al surf ace area of t he occipit al cort ex (as much as
50%-60%) [51, 73, 117, 179] . O ccipit al inf arct s in t he dist ribut ion of t he
post erior cerebral art ery are a common cause of such f ield def ect s and are most
commonly due t o emboli t o t he basilar apex (e. g. , f rom a cardiac source, or
vert ebrobasilar at herosclerot ic occlusive disease) [144] .
Pat ient s w it h purely occipit al lesions are part ially or f ully aw are of t he
hemianopia, w hereas pat ient s w it h larger or more ant erior lesions, aff ect ing
pariet al regions or associat ive pat hw ays t o t he primary or secondary visual
associat ion cort ex, may be unaw are of t heir def icit [92] . Celesia et al. , how ever,
st udied prospect ively 32 consecut ive pat ient s w it h homonymous f ield def ect s due
t o ischemic inf arct s and f ound hemianopic anosognosia, def ined as t he
unaw areness of visual loss in t he homonymous hemif ield (or hemiquadrant ), in 20
pat ient s (62%) [23] . Hemianopic anosognosia occurred predominant ly in right -
sided lesions (16/ 26 pat ient s or 62%), but w as also present in f our of six
pat ient s (or 67%) w it h lef t -sided lesions. Hemianopic anosognosia w as
associat ed
w it h somat ic anosognosia in nine pat ient s and hemineglect in 17 pat ient s. Eight
pat ient s had pure homonymous hemianopia w it hout cognit ive, mot or, or
somat osensory def icit s, f our of t hese pat ient s had aw areness of t he visual
def ect , and t hree pat ient s had hemianopic anosognosia. Pat ient s in t hese t w o
groups had similar anat omic lesions. Pat ient s w it h phosphenes, phot opsias, or
visual hallucinat ions w ere usually aw are of t heir visual f ield loss. The aut hors
suggest t hat hemianopic anosognosia is most of t en relat ed t o f ailure of t he
discovery of t he def icit s, occasionally w it h severe visual hemineglect , somet imes
t o generalized cognit ive impairment , or t o a combinat ion of t hese f act ors. The
aut hors f urt her conclude t hat (a) t here is no specif ic cort ical area f or conscious
visual percept ion; (b) visual aw areness is processed by a dist ribut ed net w ork
including mult iple visual cort ices, pariet al and f ront al lobes, t he pulvinar, and t he
lat eral geniculat e bodies (lesions localized at various nodes or cent ers in t he
net w ork may produce similar phenomena); and (c) bot h hemispheres are involved
in visual processing and conscious aw areness [23] .
Lesions of t he st riat e cort ex may be classif ied int o ant erior, int ermediat e, and
post erior locat ions [9, 73, 102, 115, 117, 119] . Ant erior lesions lie adjacent t o
t he pariet o-occipit al f issure and aff ect t he monocular t emporal crescent of t he
cont ralat eral visual f ield (t emporal crescent or half -moon syndrome) [102] . This
area const it ut es <10% of t he t ot al surf ace area of t he st riat e cort ex.
Conversely, t he t emporal crescent may be spared w it h lesions t hat dest roy t he
ent ire calcarine cort ex except f or t he ant erior t ip [102, 106] . Post erior lesions
are locat ed in t he post erior 50% t o 60% of t he st riat e cort ex, including t he
occipit al pole and operculum, and aff ect macular vision (i. e. , t he cent ral 10
degrees in t he cont ralat eral hemif ield). I nt ermediat e lesions lie bet w een t he
ant erior and post erior conf ines and aff ect f rom 10 t o 60 degrees in t he
cont ralat eral hemif ield (Figs. 7-9 and 7-10) [73, 116] .
G ray et al. report t w o pat ient s w it h unique homonymous hemianopias f rom
occipit al lesions [50] . O ne pat ient had vert ical meridian sparing and t he ot her
displayed horizont al meridian sparing. Magnet ic resonance imaging (MRI )
correlat ion w it h t he def ect s conf irmed t hat t he vert ical hemianopic meridian is
represent ed along t he border of t he calcarine lip and t he horizont al meridian lies
at t he base of t he calcarine banks deep w it hin t he calcarine f issure. G alet t a and
G rossman report ed t w o pat ient s f urt her demonst rat ing t hat t he horizont al
meridian is represent ed at t he calcarine f issure base in t he primary visual cort ex
[ 43] .
The most common cause of unilat eral occipit al disease is inf arct ion in t he
dist ribut ion of t he post erior cerebral art ery [5, 6, 9, 42, 45, 115, 144, 153] .
O t her et iologies include venous inf arct ion, hemorrhage, art eriovenous
malf ormat ion and f ist ulas, t umor, abscess, and t rauma [4, 97, 109, 120, 121,
170] .
Bilat eral occipit al lobe lesions may occur f rom a single or f rom consecut ive
event s and may cause bilat eral homonymous scot omas, usually w it h some
macular sparing (“ring” scot omas), t hat respect t he vert ical midline [68, 119] . I n
some cases t here may be “keyhole” f ields w it h bilat eral complet e homonymous
hemianopias except f or macular sparing. Caref ul t est ing in t hese cases reveals
t hat t he macular sparing respect s t he vert ical midline. Bilat eral lesions aff ect ing
t he superior or inf erior calcarine cort ices may produce bilat eral alt it udinal
def ect s t hat may mimic t he visual f ield abnormalit ies seen w it h bilat eral opt ic
nerve or ret inal disease [61, 99, 127] .
Bi l ateral homonymous hemi anopi a (double hemianopia) may occur f rom a single
or f rom consecut ive event s and may result in corti cal blindness. Cort ical
blindness is most of t en due t o simult aneous or successive post erior cerebral
art ery occlusion. There are many et iologies of cerebral and cort ical blindness,
including hypoxia, inf arct ion, hemorrhage, eclampsia, preeclampsia, hypert ensive
encephalopat hy, t ent orial herniat ion f rom cerebral mass, t umor, art eriovenous
malf ormat ion, inf ect ion (e. g. , progressive mult if ocal leukoencephalopat hy,
Creut zf eldt -Jacob disease, subacut e sclerosing panencephalit is, human
immunodef iciency virus encephalit is, syphilis, encephalit is, abscess),
inf lammat ion (e. g. , sarcoidosis), demyelinat ing disease, t rauma, migraine,
met abolic disorders (e. g. , adrenoleukodyst rophy, hypoglycemia, porphyria,
mit ochondrial encephalopat hies), t oxins (e. g. , lead, mercury, et hanol, carbon
monoxide), alcoholic ket oacidosis, medicat ions (e. g. , cyclosporine, t acrolimus,
int erleukin-2), reversible post erior leukoencephalopat hy syndrome (e. g. , due t o
t hrombot ic t hrombocyt openic purpura, hypert ension, preeclampsia, drugs),
radiat ion encephalopat hy, Alzheimer's disease, post ict al af t er seizures, and
complicat ions of cerebral angiography [2, 87] . These pat ient s may be lef t w it h a
small cent ral f ield around t he point of f ixat ion (macul ar spari ng or keyhol e
vi si on) or may have complet e blindness. O ccasionally, pat ient s w it h cort ical
blindness deny t heir visual def ect (Anton's syndrome).
Other Changes in Visual Perception

Pat ient s w it h lesions in t he ant erior opt ic pat hw ays usually complain of diff icult y
in reading and t he dimming of vision. Alt it udinal f ield def ect s are
of t en described as a curt ain coming dow n or t he sensat ion of looking over t he

horizon. Vert ical hemianopic def ect s are of t en det ect ed w hen t he pat ient f inds
himself colliding w it h object s in t he blind f ield or is unable t o see half of t he page
or t he keyboard. O t her, less common subject ive complaint s also have some
localizing value.
Metamorphopsi a (object s appearing misshapen), mi cropsi a (object s appearing
reduced in size), and macropsi a (object s appearing enlarged) may be due t o
ret inal disease, w hich causes displacement of t he recept or cells. Micropsia is
probably relat ed t o excessive separat ion of t he phot orecept ors by edemat ous
f luid (macular edema), w hereas ret inal macropsia is caused by t he ret inal
phot orecept ors being closer t oget her t han normal (e. g. , f rom macular scarring).
Micropsia may rarely occur w it h lesions of t he opt ic chiasm. I rregular dist ort ion
(irregular met amorphopsia) result s w hen t he phot orecept ors are no longer evenly
spaced (e. g. , scarring of t he ret ina or ret inal t ract ion). Dist ort ed percept ion of
t he shape and size of object s can also occur w it h occipit al or t emporal lobe
disease. I n t his case t he mispercept ion is of t en t ransient because it is linked t o
t he prodroma of migraine or t o f ocal seizures. Hemi mi cropsi a is a rare disorder
of visual percept ion charact erized by an apparent reduct ion of t he size of object s
w hen present ed in one hemif ield [29] . Hemimicropsia may result f rom
cont ralat eral f ocal lesions aff ect ing t he unimodal visual associat ion cort ex in
areas 18 and 19 and t he underlying w hit e mat t er [29] .
O N may cause movement phosphenes (a sensat ion of f lashes of light w hen
moving t he eyes in t he dark) [32] . This phenomenon may originat e w it hin t he
opt ic nerve and represent t he visual equivalent of Lhermit t e's sign [32] (see
Chapt er 5) w it h t he increased mechanosensit ivit y of t he area of demyelinat ion
result ing in “spont aneous” impulse generat ion. Persist ent phot ophobia may
occasionally be a sympt om of compressive lesions of t he chiasm [86] .
Albinism, cone degenerat ion, achromat opsia, and corneal, lent icular, and vit reous
opacit ies may cause a painless int olerance of t he eyes t o bright light , called
dazzl e [ 58] . Central dazzle may occur w it h lesions of t he opt ic nerves, chiasm,
t halamus, occipit ot emporal region, or brainst em [30, 34, 151] . Cent ral dazzle
has even been described w it h t rigeminal sensory neuropat hy secondary t o a
lesion in t he t rigeminal nucleus [58] .
Pat ient s w it h chiasmat ic lesions and bit emporal hemianopia may lose cent ral
vision w hen t heir eyes converge, because convergence makes t he bit emporal
def ect s overlap. This def icit st ands in t he w ay of act ivit ies such as t hreading a
needle or draw ing. Chiasmat ic lesions may also cause image displacement in t he
absence of damage t o t he ocular mot or nerves. Small mot or imbalances, w hich
are easily compensat ed by binocular f ixat ion w hen t he f ields are f ull, are
manif est in t he presence of a bit emporal def ect by horizont al or vert ical
deviat ion of t he images f rom eit her eye (hemi f i el d sl i de phenomenon).
Bilat eral post erior brain lesions aff ect ing t he lat eral t emporo-occipit al cort ex and
underlying w hit e mat t er, especially t he upper part of t he occipit al gyri and
adjacent port ion of t he middle t emporal gyri, may cause an unusual and severe
dist urbance of movement vision [180] . This disorder is charact erized by a
diff icult y in perceiving mot ion st imuli in general, w hereby all moving object s
induce very unpleasant and dist urbing experiences, especially w hen moving at
higher velocit ies. The select ivit y of t he movement vision def icit and t he
irreversibilit y of t he disorder support t he idea t hat movement vision is a separat e
f unct ion t hat is subserved by a visual pat hw ay specialized f or t he processing of
visual mot ion [180, [ 181] .
Objective Findings with Lesions of the Optic Pathways

I n addit ion t o neurologic abnormalit ies, such as ocular mot or paresis or
hemiparesis, t hat are due t o t he involvement of neighboring st ruct ures, lesions in
t he opt ic pat hw ays may bet ray t heir presence by changes in t he appearance of
t he opt ic nerve or ret ina or by impairment of t he aff erent arc of t he light ref lex.
Ophthalmoscopic Appearance of the Retina and Optic
Nerve
Lesions of t he ret ina and opt ic nerve may produce ident ical visual f ield def ect s
and loss of visual acuit y. How ever, ret inal lesions are of t en apparent on
opht halmoscopic examinat ion. Chronically increased int raocular pressure in
glaucoma result s in cupping of t he opt ic disc. This f inding is evident by t he t ime
visual acuit y decreases or arcuat e scot omas appear.
Many opti c nerve lesions cause an init ial sw elling of t he opt ic nerve head,
appreciable w it h t he opht halmoscope, f ollow ed in t ime by opt ic at rophy. I n
general, t he appearance of t he opt ic nerve (e. g. , normal, sw ollen, or pale) is not
specif ic and cannot diff erent iat e among various possible et iologies f or opt ic
neuropat hy. Trobe et al. review ed 163 color f undus phot ographs of several
ent it ies result ing in opt ic at rophy, including glaucoma, CRAO , I O N, O N,
heredit ary opt ic neuropat hy (Leber's and non-Leber's t ypes), compressive
opt ic neuropat hy, and t raumat ic opt ic neuropat hy [167] . These phot ographs w ere
review ed by f ive opht halmologist s as “unknow ns”. G laucoma, CRAO , and I O N
w ere correct ly ident if ied as t he et iology by at least one of t he f ive observers
w it h an accuracy above 80%, but t he remaining et iologies w ere correct ly
ident if ied in <50% of cases! Helpf ul f eat ures in diff erent iat ing t he ent it ies
included t he f ollow ing:
1. The presence of ret inal art eriolar at t enuat ion and sheat hing in ischemic
lesions (e. g. , CRAO or I O N)
2. Temporal pallor in ent it ies select ively involving cent ral vision and cent ral
visual f ield w it h sparing of peripheral visual f ield (e. g. , O N and t oxic opt ic
neuropat hies)
3. Superior or inf erior (sect or) opt ic disc pallor in I O N
Alt hough opt ic disc cupping w as of t en ident if ied in glaucoma, it w as also seen in
20% of cases not associat ed w it h glaucoma. O pt ic disc cupping in glaucoma
cases, how ever, w as more prof ound t han in nonglaucomat ous cases and great er
neuroret inal rim pallor occurred in t he nonglaucomat ous cases. I n pat ient s w it h
glaucoma, t here is of t en absence of at least part of t he neuroret inal rim and t he
color of t he remaining rim is normal. Wit h nonglaucomat ous opt ic neuropat hy,
rarely is any area of t he rim complet ely absent and t he remaining rim is of t en
pale. I nt erest ingly, only 11% of t hese cases w it h a know n hist ory of papillit is or
I O N had suff icient clues t o ident if y previous disc sw elling [167] . Anot her st udy
suggest ed t hat opt ic disc appearance may help diff erent iat e AI O N f rom O N
alt hough t here are overlapping f eat ures [172] . Alt it udinal disc sw elling w as more
t han t hree t imes more common in AI O N t han O N, alt hough most discs w ere
diff usely sw ollen. Most pat ient s w it h AI O N had hemorrhages, w hile most O N
cases did not . Almost all discs w it h O N had normal color or w ere hyperemic;
only 35% of discs w it h AI O N had pallid sw elling. Pallid sw elling w as so rare in
O N, how ever, in t hat of t he discs w it h pallor, 93% had AI O N. Art erial at t enuat ion
w as also much more t ypical of AI O N. AI O N w as t he clinical diagnosis in 82% of
cases w it h alt it udinal edema, in 81% of t he cases w it h disc hemorrhage, in 93%
of t he cases w it h pallid edema, and in 90% of t he cases w it h art erial
at t enuat ion. A pale nerve w it h hemorrhage, regardless of t he t ype of edema,
alw ays represent ed AI O N (100%). A normal color nerve w it hout hemorrhage
ref lect ed O N in 91% of t he cases, increased f rom only 76% if hemorrhage w as
not considered. A hyperemic nerve w it h hemorrhage represent ed AI O N in 82% of
cases, but if alt it udinal edema w as also present , AI O N incidence increased t o
93%.
Papi l l edema (opt ic disc sw elling secondary t o increased int racranial pressure
f rom any cause) is manif est by disc hyperemia (dilat at ion of capillaries in t he
disc surf ace), disc sw elling, loss of venous pulsat ions, and blurring of t he disc
margins, f ollow ed lat er by associat ed ret inal hemorrhages and exudat es [119] .
The presence of venous pulsat ions synchronous w it h t he art erial pulse is a
reliable indicat or of int racranial pressure below 180 t o 190 mm of w at er; absent
venous pulsat ions may be f ound in normal individuals and in pat ient s w it h
increased int racranial pressure [108] . Syndromes causing increased int racranial
pressure are out lined in Table 7-4 [ 104] .
The clinical f eat ures and clinical st ages of papilledema are out lined in Tables 7-5
and 7-6.
Pat ient s w it h a hist ory of a vent riculoperit oneal shunt f or hydrocephalus may
develop papilledema and visual loss or signs of a dorsal midbrain syndrome (see
Chapt er 8) due t o shunt f ailure. Usually comput ed t omography or MRI reveals
recurrence of t he hydrocephalus. How ever, in some individuals shunt malf unct ion
may occur w it hout apparent vent riculomegaly, perhaps due t o “st iff vent ricles”
[ 85, 103, 129] . Shunt revision is, t heref ore, indicat ed w hen t here are signs or
sympt oms of increased int racranial pressure, even if vent riculomegaly is absent ,
t o prevent
det eriorat ion of visual f unct ion and pot ent ially irreversible visual loss.
TABLE 7-4 Syndromes Causing Increased Intracranial

Pressure
Primary causes
Idiopathic pseudotumor cerebri syndrome (idiopathic
intracranial hypertension) with papilledema
Idiopathic pseudotumor cerebri without papilledema
Secondary causes
Hydrocephalus
Shunt failure in patient with hydrocephalus
(ventriculomegaly may be absent)
Mass lesions—tumor, hemorrhage, large infarction,
abscess
Meningitis/encephalitis
Subarachnoid hemorrhage
Trauma
High flow arteriovenous malformations with overloading
venous return
Intracranial or extracranial venous obstruction
Secondary pseudotumor cerebri syndrome due to
certain systemic diseases, drugs, or pregnancy
TABLE 7-5 The Clinical Features of Papilledema
Usually bilateral but may be unilateral or asymmetric

Usually preserved visual acuity and color vision
early
May have transient visual loss lasting seconds
(obscurations of vision)
Visual field defects
Enlarged blind spot
Generalized constriction
Glaucomatous-like defects
Eventual peripheral constriction, especially
nasally
No afferent pupillary defect unless there is severe
and asymmetric disc edema
Fluorescein angiography
Early disc capillary dilation, dye leakage, and
microaneurysm formation
Late leakage of dye beyond disc margins
May be normal in early papilledema
Echography may show increased diameter of optic
nerve with fluid in the optic nerve sheath

True disc sw elling must be dist inguished f rom pseudopapi l l edema and
anomal ousl y el evated di scs caused by opti c nerve head drusen [ 98, 110, 149] .
Pseudopapilledema, w it h or w it hout opt ic disc drusen, is not an uncommon
condit ion. Drusen of t he disc may be obvious, t iny, or buried. O pht halmoscopic
crit eria t hat dist inguish pseudopapilledema f orm t rue papilledema include t he
f ollow ing [47] :
1. An absent cent ral cup w it h small disc diamet er

2. Vessels arise f rom t he cent ral apex of t he disc
3. Anomalous branching of vessels, increased number of disc vessels, venous
pulsat ions present
4. Disc may be t ransilluminat ed, w it h glow of drusen w hen present
5. Disc margins irregular w it h derangement of peripapillary ret inal pigment
epit helium
6. Absence of superf icial capillary t elangiect asia
7. No hemorrhages (rare except ions)
8. No exudat es or cot t on w ool spot s
O t her disc anomalies t hat may be mist aken f or papilledema include “crow ded” or
hyperopic discs and t ilt ed discs. I n t hese cases, t he peripapillary nerve f iber
layer and t he ret inal vessels t hat t raverse it remain normal, venous pulsat ions
are usually present , t here is no vascular engorgement or hemorrhages, t here are
no cot t on w ool spot s, and t he discs do not leak dye on f luorescein angiography.
Myelinat ed nerve f ibers may occasionally resemble disc sw elling but are
charact erized by a w hit e f eat hery appearance. Hyaloid t ract ion on t he opt ic disc
and epipapillary glial t issue may also occasionally be mist aken f or disc sw elling.
When a lesion aff ect s bot h opt ic nerves successively, opt ic at rophy may be seen
in t he eye involved earlier w hile t he ot her st ill has disc edema (Foster-Kennedy
syndrome). True Fost er-Kennedy syndromes are associat ed w it h depression or
loss of t he sense of smell. Fost er-Kennedy syndrome due t o a basof ront al t umor
(e. g. , olf act ory groove meningioma) may result f rom direct compression of t he
opt ic nerve on t he side of t he lesion, w hereas cont ralat eral papilledema is due t o
increased int racranial pressure. Bilat eral direct opt ic nerve compression is a
more common cause; how ever, t he syndrome may even occur w it h longst anding
increased int racranial pressure w it hout direct opt ic nerve compression [174] .
Pit uit ary adenoma may rarely cause t he Fost er-Kennedy syndrome [95] . Alt hough
classically described w it h f ront al lobe t umors on t he side of t he opt ic at rophy, a
pseudo-Foster-Kennedy syndrome occurs more of t en w it h bilat eral and
sequent ial O N, AI O N, arachnoidit is, syphilis, and occult t rauma [155] . Lesions in
t he chiasm, opt ic t ract , or lat eral geniculat e body may also induce opt ic at rophy.
St riking opt ociliary shunt vessels may appear in t he region of t he disc or at t he
disc margins in cases of chronic increased pressure in t he opt ic canal or cranial
cavit y. They represent anast omot ic channels bet w een t he cent ral ret inal vein and
t he peripapillary choroidal venous syst em, w hich are enlarged in an eff ort t o
bypass t he compressed venous channels of t he opt ic nerve. They are most
commonly seen w it h cent ral ret inal vein occlusion or opt ic nerve sheat h
meningiomas but also occur w it h opt ic nerve glioma, neonat al hydrocephalus,
pseudot umor cerebri, drusen of t he opt ic disc, glaucomat ous opt ic at rophy, high
myopia, chronic at rophic papillit is, arachnoid cyst of t he opt ic nerve,
neurof ibromat osis, opt ic nerve coloboma, and ost eosclerosis [114] .
Because t he nerve f iber layer of t he ret ina is composed of axons of ganglion
cells on t heir w ay t o t he lat eral geniculat e body, any lesion bet w een t his nucleus
and t he eye may cause changes in t he opht halmoscopic appearance of t he f iber
layer. These changes, bet t er appreciat ed w it h red-f ree light , may have one of
f our basic pat t erns: slit or rake def ect s,
sect or at rophy, diff use at rophy, or densit y changes in t he nerve f ibers

t hemselves [125] . Because t he course of t he axons t hrough t he ant erior opt ic
pat hw ays is know n, t he ret inal dist ribut ion of t hese changes may suggest t he
locat ion of t he process. For inst ance, chi asmati c lesions aff ect t he f ibers nasal
t o t he opt ic disc and t hose nasal t o t he macula (papillomacular bundle; Figs. 7-1
and 7-2). As a result , sect or at rophy occurs at bot h sides of t he disc, and t he
remaining f ibers, somew hat t hinned out , adopt t he shape of a vert ically disposed
bow t ie, w it h t he knot at t he opt ic disc. This pat t ern is present in bot h eyes w hen
t he lesion is in t he chiasm but may appear in only one eye, t he one cont ralat eral
t o t he lesion, w hen t he lesion is in t he opt ic t ract or geniculat e body [154] .
TABLE 7-6 The Stages of Papilledema
1. Early papilledema
Minimal disc hyperemia with capillary dilation
Early opacification of nerve fiber layer
(peripapillary retina loses its superficial linear
and curvilinear light reflex and appears red
without luster)
Early swelling of disc
Absence of venous pulsations
Peripapillary retinal nerve fiber layer hemorrhage
2. Fully developed papilledema
Engorged and tortuous retinal veins
May have splinter hemorrhages at or adjacent to
the disc margin
Disc surface grossly elevated
Surface vessels become obscured by now opaque
nerve fiber layer
May have cotton wool spots
Paton's lines (circumferential retinal folds) or
choroidal folds
May have exudates (e.g., macular star or
hemistar)
May have hemorrhages or fluid in the macula that
may decrease vision
In acute cases (e.g., subarachnoid hemorrhage),
subhyaloid hemorrhages may occur that may
break into vitreous (Terson's syndrome)
Rarely macular or peripapillary subretinal
neovascularization
3. Chronic papilledema
Hemorrhages and exudates slowly resolve
Central cup, which is initially retained even in
severe cases, ultimately becomes obliterated
Initial disc hyperemia changes to a milky gray
Small hard exudates that are refractile and
drusen-like may appear on disc surface
Visual field loss including nerve fiber layer
defects may develop
Optociliary “shunt” (collaterals) vessels may
develop
4. Atrophic papilledema (pale disc edema)
Optic disc pallor with nerve fiber bundle visual
field defects
Retinal vessels become narrow and sheathed
Occasional pigmentary changes or choroidal folds
in macula
Selective loss of peripheral axons while sparing
central axons (usually preservation of good
central visual acuity)

Pupillary Light Reflex

The f ibers t hat const it ut e t he aff erent arc of t he pupillary light ref lex leave t he
visual sensory pat hw ay just bef ore t he lat eral geniculat e body, w it hout synapsing
in it , t o reach t he dorsal midbrain. Ret inal lesions must be quit e large t o impair
t he light ref lex, but changes in pupillary responses, part icularly t he so-called
RAPD or Marcus G unn pupi l, are very helpf ul in det ect ing asymmetri c opti c
nerve or chi asmati c lesions. This pupillary sign is charact erized by a normal
bilat eral pupillary response w hen t he sound eye is illumined, but pupillary
dilat at ion occurs w hen t he f lashlight is quickly sw it ched t o t he diseased side
[ 162] . Anisocoria larger t han 2 mm in diamet er may induce a small clinically
RAPD in t he eye w it h t he smaller pupil [101] . O pt ic t ract disease may cause a
modest RAPD w hen t he light is direct ed int o t he eye cont ralat eral t o t he lesion
(i. e. , t he eye w it h t he t emporal f ield def ect ) because t he t emporal visual f ield is
61% t o 71% larger t han t he nasal f ield and t he rat io of crossed t o uncrossed
f ibers in t he chiasm is 53 t o 47 [130] . RAPD wi thout visual dysf unct ion may occur
w it h lesions t hat select ively int errupt t he pupillary aff erent s t o t he
pret ect al nucleus (e. g. , lesions of t he brachium of t he superior colliculus) or

damage t he pret ect al nucleus it self [44, 90] . RAPD w it hout visual dysf unct ion
has been described w it h cerebral inf arct ion, t umors of t he pineal region, t halamic
t umors, t halamic and midbrain glioma, and brainst em art eriovenous
malf ormat ions [26, 36, 39, 82, 90] . A lesion aff ect ing t he brachium of t he
superior colliculus and t he adjacent t rochlear nucleus or f ascicle (e. g. ,
mesencephalic ast rocyt oma) may cause a cont ralat eral RAPD w it hout visual
impairment and a cont ralat eral superior oblique paresis [35] . Theref ore, an
RAPD may occur w it h disease of t he macula, ret ina, opt ic nerve, opt ic chiasm,
opt ic t ract , brachium of t he superior colliculus, or pret ect al nucleus [37] (Table
7-7). Macular disease must be subst ant ial and usually easily visualized on
f unduscopic examinat ion t o produce an RAPD. Lateral geni cul ate body lesions
and t hose in t he geni cul ocal cari ne segment of t he opt ic sensory pat hw ays leave
t he pupillary light ref lex unimpaired. I n f unct ional visual loss, t here is no RAPD.
Cat aract s, even w hen very dense and pigment ed, produce lit t le or no RAPD and,
in f act , of t en increase t he pupillomot or eff ect iveness of light [100, 162] .
Theref ore, an RAPD may occur cont ralat eral t o an eye w it h a unilat eral dense
cat aract , w it h t he RAPD disappearing af t er cat aract ext ract ion [100] . I f an RAPD
is f ound in an eye w it h a cat aract , a visual pat hw ay def ect should be suspect ed.
An RAPD may occur in an eye w it h bet t er visual acuit y w hen visual loss is due t o
abnormalit y of t he ocular media (e. g. , corneal opacit y, hyphema, ant erior
segment membrane, cat aract , or vit reous opacit y), amblyopia, ref ract ive error,
age-relat ed macular degenerat ion, or cyst oid macular edema [18] . An RAPD is
not proport ional t o visual acuit y loss but may be proport ional t o visual f ield loss
[ 83, 163] .
TABLE 7-7 Etiologies of a Relative Afferent Pupillary

Defect
Optic nerve disease (unilateral, or, if bilateral,
asymmetric)
Large amount of retinal disease (usually visible with
ophthalmoscope)
Optic tract (contralateral)—more crossed than
uncrossed fibers (ratio 53:47 of crossed to
uncrossed fibers)
Rarely amblyopia or vitreous hemorrhage
Contralateral RAPD may occur due to pretectal
lesion without visual field loss (e.g., damage to
brachium of superior colliculus or pretectal nucleus
itself)
Anisocoria + RAPD must = two separate processes
Visual loss from cataracts, corneal disease, or
media difficulties does not cause RAPD
RAPD = relative afferent pupillary defect.
Optic Neuropathy
The diagnosis of opt ic neuropat hy is usually made on clinical grounds alone. The
clinical f eat ures of opt ic neuropat hies are summarized in Table 7-8 [ 104] .
Tw o of t he most common causes of acut e opt ic neuropat hy are AI O N and O N.
Alt hough t here is considerable overlap in t heir clinical present at ion, age can be
used as an init ial diff erent iat ing f eat ure in many cases [146] . I n younger pat ient s
(<40 years old) w it h acut e unilat eral opt ic disc edema and evidence of opt ic
neuropat hy, O N is more likely t han AI O N. Conversely, in t he older pat ient w it h
acut e opt ic disc edema and visual loss, AI O N is more common.
Optic Neuritis
O N is an inf lammat ory or aut oimmune disease process aff ect ing t he opt ic nerve
causing relat ively acut e impaired vision, progressing over hours or days [47] .
Visual f unct ion is low est by 1 w eek, and t he disease process is predominant ly
unilat eral. O N is more common in w omen (77%) and usually aff ect s pat ient s w ho
are 20 t o 50 years of age (mean age, 32 years) [135] . Pain, of t en induced or
exacerbat ed by eye movement , accompanies visual loss in >90% of pat ient s
[ 135] . The opt ic disc is normal in approximat ely t w o-t hirds of pat ient s
(retrobul bar O N) and sw ollen in one-t hird [135] . Color vision is of t en aff ect ed
more
t han visual acuit y [122a. Visual f unct ion is especially decreased in t he cent ral 20
degrees of t he visual f ield, w it h various abnormalit ies not ed on perimet ry [88] . I n
most pat ient s, vision improves in t he second or t hird w eek and is of t en normal by
t he f ourt h or f if t h w eek. How ever, some pat ient s do not improve t o a f unct ional
level or at all. The clinical f eat ures of t ypical O N are out lined in Table 7-9.
TABLE 7-8 The Clinical Features of Optic Neuropathy
Decreased visual acuity

Decreased color vision
Visual field defect
Ipsilateral relative afferent pupillary defect in
unilateral or bilateral, asymmetric cases
Light-near dissociation of the pupils in bilateral and
symmetric cases
Optic disc edema or disc atrophy (although the optic
nerve may appear normal in retrobulbar optic
neuropathy)
O N is t he present ing f eat ure in 25% of pat ient s w it h MS and occurs at some
st age of t he disease in 73%. I n a st udy of 60 New England w hit es w it h isolat ed
O N, t he risk of clinical MS developing in 15 years w as 69% f or w omen and 33%
f or men [145] . I n anot her st udy, lif e-t able analysis show ed t hat 39% of pat ient s
w it h isolat ed O N progress t o clinically def init e MS by 10 years of f ollow -up; 49%
by 20 years; 54% by 30 years; and 60% by 40 years [147] . This lat t er st udy did
not not e any diff erence in t he risk of developing MS bet w een men and w omen. I n
t he O pt ic Neurit is Treat ment Trial, a prospect ive st udy of 388 pat ient s w ho did
not have probable or def init e MS at st udy ent ry, t he 5-year cumulat ive
probabilit y of clinically def init e MS w as 30% [136] . Brain MRI s perf ormed at
st udy ent ry w ere a st rong predict or of t he development of MS, w it h t he 5-year
risk of clinically def init e MS ranging f rom 16% in 202 pat ient s w it h no MRI
lesions t o 51% in 89 pat ient s w it h t hree or more MRI lesions. The O pt ic Neurit is
St udy G roup f urt her st udied 388 pat ient s w ho experienced acut e O N and
f ollow ed up prospect ively f or t he development of MS [137] . The 10-year risk of
MS w as 38%. Pat ient s (160) w ho had one or more t ypical lesions on t he
baseline MRI of t he brain had a 56% risk; t hose w it h no lesions (191) had a 22%
risk.
TABLE 7-9 Features of Typical Optic Neuritis
Acute, usually unilateral loss of vision

Visual acuity (variable visual loss 20/20 to no light
perception)
Visual field (variable optic nerve visual field defects)
A relative afferent pupillary defect in unilateral or
bilateral but asymmetric cases
Periocular pain (90%), especially with eye movement
Normal (65%) or swollen (35%) optic nerve head
A young adult patient (< 40 y) but optic neuritis may
occur at any age
Eventual visual improvement
Improvement over several weeks in most patients
(90%) to normal or near normal visual acuity
88% improve at least one Snellen line by d 15
96% improve at least one line by d 30
Visual recovery may continue for months (up to 1 y)
Patients may complain of residual deficits in
contrast sensitivity, color vision, stereopsis, light-
brightness, visual acuity, or visual field

Uhthof f 's symptom (w orsening of vision under bright light or w it h exercise) may
occur w it h O N; it s presence may be a prognost ic indicat or f or t he early
development of MS [156] . O ccasionally, a chiasmat ic syndrome may occur w it h
O N (chiasmal neurit is) [128] .
Anterior Ischemic Optic Neuropathy

AI O N is t he most f requent cause of opt ic disc sw elling in adult s older t han 50
and usually aff ect s individuals in t he sixt h t o eight h decades [12, 79] . I t is due t o
t he occlusion of t he post erior ciliary art ery, w hich may be due t o at herosclerosis
(nonarteri ti c AIO N) or t emporal (giant cell) art erit is (arteri ti c AIO N). AI O N may
also occur w it h collagen vascular diseases, t he ant iphospholipid ant ibody
syndrome, diabet es, migraine, and w it h acut e blood loss, surgery, or af t er
cat aract ext ract ion. [104] . Wit h AI O N t here is an acut e or subacut e, usually
painless loss of vision w it h a sudden visual f ield def ect , usually an alt it udinal
(especially inf erior) def ect [12, 79] . A small cup t o disc rat io (“disc at risk”) in
t he f ellow eye is a predisposing f act or t o nonart erit ic AI O N [20] . The opt ic disc
is sw ollen and of t en pale, usually w it h small peripapillary f lame-shaped
hemorrhages. I n cont rast t o O N, visual loss is usually permanent w it h
subsequent opt ic at rophy, alt hough 32. 6% of pat ient s improve somew hat over a
6-mont h period [79] . The clinical f eat ures of t ypical nonart erit ic AI O N are
out lined in Table 7-10. Art erit ic AI O N diff ers f rom nonart erit ic AI O N by aff ect ing
older pat ient s, by it s associat ion (in 10% of pat ient s) w it h premonit ory t ransient
visual sympt oms (amaurosis f ugax), by it s causing more prof ound visual loss, by
it s associat ion w it h ot her sympt oms (headache, jaw claudicat ion, and
polymyalgia rheumat ica), by it s associat ion w it h an elevat ed eryt hrocyt e
sediment at ion rat e or C-react ive prot ein, and by evidence t hat st eroid t reat ment
prevent s visual loss in t he f ellow eye [12, 64, 65, 66, 104] . I O N present ing
w it hout disc sw elling (posteri or IO N) is uncommon but it s occurrence should
alw ays raise a concern f or giant cell art erit is as t he et iology.
TABLE 7-10 Typical Clinical Features of Nonarteritic

Anterior Ischemic Optic Neuropathy
Age usually > 40 y

Unilateral variable loss of visual acuity and/or visual
field
Visual field defects consistent with an optic
neuropathy (e.g., central, cecocentral, arcuate, or
altitudinal)
Optic disc edema (usually pallid edema) in the acute
phase followed by optic atrophy that may be sector
or diffuse
Relative afferent pupillary defect in unilateral or
bilateral but asymmetric cases
Small cup and cup to disc ratio (< 0.2) and optic
nerve head circulatory abnormalities
Often associated with underlying vasculopathic risk
factors (e.g., hypertension, diabetes, smoking,
ischemic heart disease, hypercholesterolemia)
Lack of premonitory symptoms (e.g., transient visual
loss)
Usually visual loss remains static but may improve
slightly or progress
End-stage optic disc appearance is segmental or
diffuse pallor without significant cupping (unlike
arteritic anterior ischemic optic neuropathy which
often shows end-stage increased optic nerve
cupping with atrophy)

The subacut e or sudden onset of visual loss in O N and I O N cont rast w it h t he

progressive visual dist urbance not ed w it h a compressive lesion of t he opt ic nerve
[ 107] . Theref ore, pat ient s w it h visual loss f rom opt ic neuropat hy must be
f ollow ed closely f or det eriorat ion in visual f unct ion t o rule out pot ent ially
correct able opt ic nerve compressive lesions.
M ass Lesions of the Orbit

Tumors of t he orbit usually cause progressive unilat eral visual f ailure t hat may
be variably associat ed w it h t he f ollow ing signs and sympt oms [119] :
1. O pt ic disc sw elling w hich is f ollow ed by at rophy.

2. O pt ociliary shunt vessels. The t riad of opt ociliary shunt veins, disc pallor,
and visual loss (t he Hoyt-Spencer si gn) i s charact erist ic of chronic opt ic
nerve compressive lesions, especially sphenoorbit al opt ic nerve sheat h
meningiomas.
3. Limit at ion of ocular movement s is seen along w it h diplopia.
4. Propt osis (prot rusion of t he eyeball). Eyeball prot rusion may also be seen
w it h disease of t he cavernous sinus and may be rarely due t o int racranial
disease (e. g. , a t umor of t he middle cranial f ossa may cause pressure on t he
veins of t he cavernous sinus leading t o secondary int raorbit al venous
congest ion and “f alse localizing” propt osis [1] ). Intermi ttent propt osis may
occur w it h venous angioma w it hin t he orbit and develops w hen t he pat ient
st rains, cries, bends t he head f orw ard, hyperext ends t he neck, coughs, or
blow s t he nose against a closed nost ril and w hen t he jugular vein is
compressed. During t hese episodes, t he eye may become t ense and painf ul,
t he pupil may enlarge, and occasional bradycardia or syncope may develop
(oculocardiac syndrome). Pul sati on of t he globe may occur w it h congenit al
sphenoid dysplasia, w it h orbit al cranial encephalocele w it h
neurof ibromat osis, f rom orbit al art eriovenous malf ormat ions or venous
varices, due t o t ricuspid regurgit at ion, w it h art erial pulsat ion of t he orbit al
vein, due t o art eriovenous f ist ula, or f rom t ransmission of pulsat ions of
int racranial pressure t hrough surgical or t raumat ic def ect s in t he orbit al w all
[ 47] .
Exophthal mos is most of t en caused by orbit al G raves' disease. Causes of
pseudoexophthal mos include an enlarged globe (e. g. , due t o myopia,
bupht halmos, or congenit al cyst ic eye), eyelid or palpebral f issure
asymmet ry (e. g. , due t o lid ret ract ion, pt osis, sevent h nerve palsy, or
post surgical eff ect ), ext raocular muscle abnormalit y (w eakness or paralysis),
shallow or asymmet ric bony orbit s, or cont ralat eral enopht halmos (e. g. ,
met ast at ic breast cancer, orbit al f loor f ract ure, or congenit al bone def ect )
[ 131] .
Rat her t han causing propt osis, scirrhous carcinoma of t he breast or
carcinoma of t he lung, gast roint est inal t ract , or prost at e met ast at ic t o t he
orbit may cause progressive f ibrot ic change and enophthal mos [ 48, 49, 164] .
This enopht halmos may be caused by post erior t ract ion and t et hering on t he
eyeball or by t he t umor mass dest roying t he orbit al w all result ing in “biologic
orbit al decompression. ” O t her causes of enopht halmos include senile orbit al
f at at rophy, t raumat ic orbit al f loor f ract ure, t raumat ic orbit al f at at rophy,
f acial hemiat rophy (Parry-Romberg disease), f acial ost eomyelit is, and orbit al
f at necrosis [47, 60] . Spont aneous enopht halmos and pt osis of t he globe
(hypoglobus), unassociat ed w it h orbit al t rauma, may be associat ed w it h
ipsilat eral chronic maxillary sinusit is
or hypoplasia (t he “si l ent si nus syndrome”) [160, 178] . The apparent

dissolut ion and resorpt ion of t he orbit al f loor causes t he loss of inf erior
support and orbit al expansion. Enopht halmos and hypoglobus unassociat ed
w it h prior t rauma, surgery, or ot her sympt oms have been called t he si l ent
si nus syndrome, w hich is ipsilat eral maxillary sinus hypoplasia and orbit al
f loor resorpt ion [160] .
TABLE 7-11 Signs and Sympto
Visual perception
Visual
Acuity; Color Visual Field
Contrast Perception Defects
Sensitivity
Corresponds
retinal damag
Normal, if
Blue affected central,
macula is
more than red cecocentral,
spared;
Retina with arcuate defec
decreased,
photoreceptor sectorial ring
if macula
lesions with nasal
is affected
step; altitudin
defects
Monocular wi
unilateral
Optic Red most
Decreased lesions; same
nerve affected
shape as
retinal lesion
Decreased
in both Anterior angl
eyes when Ipsilateral—
the medial temporal or
part of the paracentral;
chiasm is contralateral—
Optic Red most
affected; upper tempor
chiasm affected
decreased Body:
in the eye Bitemporal,
ipsilateral often only
to a lateral superior or
chiasmatic paracentral
lesion
Normal Red most Contralateral

Optic with affected in homonymous
tract unilateral areas of visual hemianopia;
lesions field loss incongruous
Contralateral
homonymous
Normal Red most
Lateral hemianopia;
with affected in
geniculate may be
unilateral areas of visual
body incongruous;
lesions field loss
quadruple
sectoranopia
Contralateral
homonymous
hemianopia
(total lesion)
quadrantanop
(interior with
Normal Red most
parietal lesio
Optic with affected in
superior with
radiations unilateral areas of visual
temporal
lesions field loss
lesion);
mascular
sparing with
purely
quadrantic
defects
Contralateral
homonymous
hemianopia,
Normal congruous;
with macula
unilateral Red most sparing;
lesions; affected; involvement o
Calcarine with achromatopsia sparing of
cortex impaired with bilateral contralateral
lesions inferomedial unpaired
affecting occipital temporal
both lesions crescent; ring
occipital shape or
poles altitudinal wit
“vertical step
in bilateral
lesions
5. Sw elling of t he eyelids and chemosis are seen.

6. G aze-evoked amaurosis. This ref ers t o loss of vision w henever t he eye is
placed in an eccent ric posit ion of gaze and has been not ed most of t en w it h
cavernous hemangiomas and opt ic nerve sheat h meningiomas [15, 138] .
G aze-evoked amaurosis has also been described w it h orbit al ost eoma,
glioma, medial rect us granular cell myoblast oma, varix, pseudot umor cerebri,
orbit al t rauma, and met ast at ic orbit al t umor [93] . This phenomenon is t hought
t o be due t o decreased blood f low t o t he ret ina or opt ic nerve w it h eye
movement (e. g. , t he mass compresses t he cent ral ret inal art ery) [91] .
Alt hough most of t en due t o int rinsic orbit al disease, gaze-evoked monocular
obscurat ions in lat eral and upw ard gaze have also been described w it h
pseudot umor cerebri [134, 140] and gaze-evoked t ransient visual loss on
upw ard gaze has been not ed w it h an int racranial int ernal carot id art ery
aneurysm [158] .
7. Several branches of t he t rigeminal nerve may be aff ect ed by orbit al disease,
especially t hose of t he opht halmic division, w hich has a large number of
branches passing t hrough t he orbit [148] . The ext ent of cut aneous sensory
loss is indicat ive of t he posit ion of t he orbit al disease, w it h t he lacrimal,
supraorbit al, or suprat rochlear nerves being aff ect ed by disease along t he
orbit al roof and t he zygomat ic and inf raorbit al nerves being aff ect ed by
diseases along t he orbit al f loor. Disease at t he orbit al apex or t he superior
orbit al f issure may cause hypest hesia aff ect ing several or even all of t he
periorbit al dermat omes. I n cont rast w it h cut aneous sensory loss, how ever,
corneal hypest hesia appears unrelat ed t o t he posit ion of disease w it hin t he
orbit [148] . I f t he t umor erodes t hrough t he f loor of t he orbit , it may damage
t he maxillary division of cranial nerve V (t he t rigeminal nerve), result ing in
ipsilat eral maxillary pain, anest hesia, or bot h, over t he dist ribut ion of t he
maxillary branch of t he t rigeminal nerve. O rbit al pain is common w it h orbit al
lesions, especially w it h orbit al malignancy or inf lammat ory disease.
G oldberg et al. [48, 49] described t he manif est at ion of orbit al met ast at ic t umors
int o f ive syndromes: (a) inf ilt rat ive—charact erized by prominent rest rict ion of
mot ilit y, a f irm orbit , pt osis, and of t en enopht halmos; (b) mass—charact erized by
propt osis, displacement of t he globe, and of t en a palpable orbit al mass; (c)
inf lammat ory—charact erized by pain, chemosis, eryt hema, and periorbit al
sw elling; (d) f unct ional—charact erized by cranial nerve f indings (e. g. , problems
w it h ocular mot ilit y) disproport ionat e w it h t he degree of orbit al involvement ; and
(e) silent —orbit al met ast at ic lesions det ect ed by comput erized t omography or
MRI but asympt omat ic. I nf ilt rat ive and mass lesions w ere by f ar t he most
common manif est at ions. Direct met ast ases t o t he orbit al muscles may occur,
especially w it h carcinoma of t he breast and malignant melanoma [21] .
This chapt er has dealt w it h t he signs and sympt oms t hat are most helpf ul in
localizing a lesion in t he opt ic pat hw ays. These signs are summarized in Table 7-
11, w hich also list s t he most likely f indings w it h lesions in each port ion of t he
visual syst em.
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> Table of C ontents > C hapter 8 - The Loc aliz ation of Les ions Affec ting the O c ular Motor S ys tem
Chapter 8
The Localization of Lesions Affecting the Ocular
Motor System
Abnormalit ies of ocular mot ilit y serve as valuable signpost s f or t he localizat ion of
lesions of t he cerebral hemispheres, brainst em, cranial nerves (CNs), and even
t he st riat ed muscle. O cular sympt oms and signs are part icularly helpf ul w hen
examining t he pat ient in coma (see Chapt er 22).
I n t his chapt er, t he t erm ocul ar motor ref ers t o CNs I I I (oculomotor), I V
(trochl ear), and VI (abducens), collect ively, w hereas t he w ord ocul omotor
designat es specif ically CN I I I . This f ollow s t he convent ion adopt ed by Leigh and
Zee [480] in t heir excellent review of ocular mot ilit y.
We f irst review t he anat omy and localizat ion of lesions of t he ocular mot or nuclei
and nerves and t hen t he cont rol syst ems t hat t he brain uses t o produce precise,
smoot h, quick, st able, and binocular eye movement s. Dist urbances of t hese
“supranuclear” mechanisms, nyst agmus, and eyelid dist urbances are t hen
discussed.
Ocular M otor M uscles and Nerves

Orbital Muscles
Each eye globe is moved by six muscles: f our rect i (superior, inf erior, medial,
and lat eral) and t w o oblique (superior and inf erior). The horizont al rect i arise
f rom t he annulus of Zinn and course along t he medial and lat eral orbit al w alls.
The act ion of t he medial (eye-in) and lat eral (eye-out ) rect i requires no f urt her
comment . The superior rect us (SR) muscle originat es f rom t he annulus of Zinn,
courses ant eriorly upw ard over t he eyeball, and lat erally, f orming an angle of 23
degrees w it h t he visual axis of t he eye. This muscle elevat es t he eye (displaces
t he cornea upw ard) w hen t he eye is deviat ed out w ard (abduct ed) (Fig. 8-1).
Likew ise, t he inf erior rect us (I R) arises f rom t he annulus, courses ant eriorly
dow nw ard and lat erally f orming an angle of 23 degrees w it h t he visual axis, and
primarily depresses t he eye most eff icient ly w hen t he globe is abduct ed. By
cont rast , w hen t he eye is adduct ed (t urned inw ard), t he SR int ort s it (moves it
count erclockw ise in t he case of t he lef t eye), and t he I R ext ort s it (moves t he
lef t eye clockw ise). The superior oblique (SO ) muscle arises f rom t he annulus of
Zinn and passes ant eriorly and upw ard along t he superomedial w all of t he orbit ,
becoming t endinous bef ore passing t hrough t he t rochlea locat ed on t he nasal
side of t he superior orbit al rim. The t endon is t hen ref lect ed inf eriorly,
post eriorly, and lat erally, f orming an angle of 51 degrees w it h t he visual axis. I t
passes inf erior t o t he SR and insert s in t he post erosuperior quadrant of t he
eyeball. The inf erior oblique (I O ) muscle originat es f rom t he periost eum of t he
maxillary bone, just post erior t o t he orbit al rim, and passes lat erally, superiorly,
and post eriorly coursing underneat h t o t he I R muscle and under t he lat eral
rect us (at an angle of 51 degrees w it h t he visual axis) t o insert in t he
post erolat eral port ion of t he globe. The oblique muscles have a similar but
complement ary act ion in moving t he eyes in t he vert ical plane. They move t he
eyeball in a vert ical plane w hen t he eye is adduct ed and act as rot at ors w hen it
is abduct ed. Unlike t he rect i, how ever, t he oblique muscles f unct ion as w ould be
expect ed f rom t he locat ion of t heir insert ional point s in t he ant erior part of t he
orbit and in t he post erior part of t he globe. The SO depresses t he eye or t w ist s
it inw ardly (count erclockw ise by examiner's view in t he case of t he lef t eye) and
t he I O el evates t he eye or ext ort s it w hen abduct ed (moves t he lef t eye
clockw ise by examiner's view ).
FI G URE 8-1 Superior view of t he right orbit . A: O n abduct ion, t he superior

rect us act s as an elevat or, and t he superior oblique (SO ) int ort s t he eye
(brings t he upper pole t ow ard t he nose). B: I n adduct ion, t he SO act s as a
depressor, and t he superior rect us int ort s t he eye. I n (B), t he superior
rect us has been removed t o show t he posit ion of t he SO
Tw o muscles, bot h in t he upper eyelid, act t oget her t o w iden t he palpebral

f issure. Müller's muscle receives sympat het ic innervat ion and is responsible f or
t he w ide st are t hat accompanies st at es of enhanced alert ness. How ever, t he
levat or of t he lid, innervat ed by CN I I I , plays t he great er role in eyelid opening.
Eye closure (orbicularis oculi) is eff ect ed t hrough CN VI I .
Diplopia
The commonest subject ive complaint elicit ed by lesions in t he ocular mot or
syst em is di pl opi a [ 115, 116] . This disorder occurs more f requent ly w it h lesions
of t he ext raocular muscles or ocular mot or nerves t han w it h supranuclear
brainst em lesions, w hich of t en result in gaze palsies. Diplopia result s f rom lack
of visual f usion. The perceived object is project ed t o noncorresponding point s of
t he ret ina and is t heref ore seen as t w o object s. O f t en, part icularly w hen t he
def ect is mild, t he pat ient sees a blurry, rat her t han a double, image.
Diplopia t hat is present monocul arl y remains present despit e covering t he f ellow
eye and t hen disappears w hen t he involved eye is occluded. I t may occur
unilat erally or bilat erally. The second image is of t en described as a less clear
and part ially superimposed “ghost image” or a “halo” on t he f irst image. A
pinhole may dramat ically reduce t he pat ient 's sympt oms. Monocular diplopia
usually implies a problem w it hin t he eye it self and may respond t o ref ract ion,
art if icial t ear t rial, or cont act lens t rial. Et iologies of monocular diplopia include
corneal and lent icular ast igmat ism and opacit ies, a f oreign body in t he aqueous
or vit reous media, ret inal disease, ocular surgery, st rabismus, or psychiat ric
disease.
Anot her f orm of monocular diplopia is cerebral pol yopi a [ 212, 348, 389, 521,
717] . Cerebral polyopia can usually be dist inguished f rom monocular diplopia due
t o ocular disease because all of t he images are seen w it h equal clarit y, t he
mult iple images do not resolve w it h a pinhole, and t he images are unchanged in
appearance w het her t he pat ient is view ing binocularly or monocularly. Some
pat ient s see only t w o images, w hile ot hers may see many or even hundreds of
images occurring in a grid-like pat t ern (“ent omopia” or “insect eye”) [499] . Some
pat ient s experience t he polyopia only in cert ain posit ions of gaze. Pat ient s w it h
cerebral polyopia of t en have associat ed signs of occipit al or pariet o-occipit al
region damage, such as homonymous visual f ield def ect s, diff icult y w it h visually
guided reaching, cerebral achromat opsia or dyschromat opsia, object agnosia,
and abnormal visual af t erimages. The mult iple images of t en appear in t he f ield
opposit e t he lesion. Cerebral inf arct ion is t he most common et iology, alt hough
cerebral polyopia may also occur w it h t umors, mult iple sclerosis, encephalit is,
seizures, and migraine [389] .
Diplopia can somet imes occur w it hout ext raocular muscle abnormalit y. For
example, t he hemi f i el d sl i de or sl i p phenomena is a rare cause of int ermit t ent
binocular diplopia not ed in some pat ient s w it h lesions of t he opt ic chiasm [435] .
This phenomenon occurs w it h complet e or nearly complet e bit emporal
hemianopic visual f ield def ect s (see Chapt er 7) w it h disrupt ion of ocular f usion
and decompensat ion of a previous phoria. The underlying pat hophysiology is loss
of binocularit y due t o lack of cort ical represent at ion of corresponding point s in
t he visual f ield f rom each eye (i. e. , t ransect ion of t he chiasm creat es t w o
independent , f ree-f loat ing hemif ields, w it h each eye project ing only t o t he
ipsilat eral visual cort ex). Pat ient s complain of int ermit t ent diplopia and diff icult y
w it h near w ork (e. g. , t hreading a needle or sew ing). O n examinat ion, no ocular
mot or palsy is not ed despit e t he pat ient s' complaint s of diplopia. I f t he eyes
int ermit t ent ly converge (esot ropia), a blank space is produced bet w een t he
vert ical meridians as t he eyes “slip” inw ards and t he remaining hemif ields drif t
apart horizont ally. O cular divergence (exot ropia) causes overlapping of t he
vert ical meridians result ing in superimposit ion
of images f rom noncorresponding ret inal areas. Hemif ield slide diplopia may also
occur f rom alt it udinal visual f ield def ect s [97] .
Testing for Diplopia

Bef ore diplopia t est ing is undert aken, it is import ant t o ascert ain visual acuit y in
bot h eyes and t o inspect t hem f or lens or ret inal displacement s. A f orced duct ion
t est may be done t o det ermine w het her t he rest rict ion of eye movement is due t o
muscle w eakness or t o mechanical rest rict ion in t he movement of t he globe. A
posit ive f orced duct ion t est (i. e. , rest rict ion of eye movement on at t empt ed
f orced duct ions) may be seen w it h t hyroid eye disease, ext raocular muscle
f ibrosis, muscle ent rapment (e. g. , blow out orbit al f ract ure), Duane's ret ract ion
syndrome, Brow n's superior oblique t endon sheat h syndrome, carot id-cavernous
sinus or dural f ist ula, and direct orbit al inf ilt rat ion.
Horizont al binocular diplopia is usually due t o disease processes aff ect ing t he
medial and/ or lat eral rect us muscles, t he innervat ion of t hese muscles (including
ocular mot or CNs and neuromuscular junct ion), or processes aff ect ing f usion or
convergence and divergence mechanisms [116] . By def init ion, pat ient s w it h
horizont al diplopia complain t hat t he t w o images are side by side. The separat ion
of images may vary or remain unchanged at f ar or near f ixat ion. For example,
t he image separat ion f rom a lef t abducens nerve palsy is t ypically w orse at
dist ance t han at near and w orse on lef t gaze. Pat ient s w it h vert ical diplopia
complain of seeing t w o images, one at op or diagonally displaced f rom t he ot her
[ 115] . I f t he pat ient complains of vert ical diplopia in primary gaze, of t en one of
t he vert ically act ing ext raocular muscles is underact ing: t he right and/ or lef t I R,
SR, I O , or SO .
To ident if y t he muscle or t he nerve involved, subject ive and object ive t est s
should be used. G reat er diff icult y w it h near vision suggest s impairment of t he
Medial Rect us (MR) muscle, oculomot or nerve, or convergence syst em.
Abducens w eakness result s in horizont al diplopia w hen view ing dist ant object s.
Vert ical diplopia becomes w orse on near vision w hen an oblique muscle is w eak.
Misalignment (deviat ion) of t he visual axis w hen only one eye is view ing is
ref erred t o as a phori a. Misalignment of t he visual axis w it h bot h eyes view ing is
called a tropi a. When strabi smus (misalignment of t he visual axes) exist s, it is
named by t he direct ion of deviat ion: if t he eyes t urn in, esodevi ati on; if t he eyes
t urn out , exodevi ati on; if one eye is dow n, hypodevi ati on; if one eye is up,
hyperdevi ati on; and if one eye is t ort ed, cycl odevi ati on. St rabismus may be
comi tant (t he deviat ion is st able in nonext remes of gaze) or i ncomi tant (t he
deviat ion varies in diff erent gaze posit ions). Eye deviat ions f rom childhood
st rabismus are t ypically comit ant , w hile most of t he acquired deviat ions are
incomit ant .
A phori a is a lat ent ocular misalignment t hat is kept in check by f usion. Fusion is
t he process of merging images f rom each eye int o a single percept ion. Sensory
f usion is t he cort ical int egrat ion of t w o images, w hile mot or f usion represent s t he
correct ive movement s of t he eyes required t o maint ain eye alignment on t he
t arget of regard. Breakdow n of f usion due t o f at igue, st ress, illness, and so on,
may allow a preexist ing phoria t o become an int ermit t ent or manif est t ropia.
Subjective Testing
Alt hough a peripheral nerve or muscle may be so severely aff ect ed t hat t he
diagnosis of ocular mot or paresis can be made by mere inspect ion of t he
posit ion of bot h eye globes in t he orbit , of t en t he object ive f indings are subt le
and subject ive diplopia t est ing is helpf ul. To ascert ain w hich image belongs t o
w hich eye, a red glass may be placed in f ront of one eye, or each eye may be
covered and uncovered alt ernat ely. I nst ead of a red glass, a simple inst rument ,
t he Maddox rod, can be used t o separat e t he t w o images even more conclusively
[ 480] . Tw o rules are t hen applied. First , image separat ion is great est in t he
direct ion of t he w eak muscle. Second, in t he posit ion of great est image
separat ion, t he image seen more peripherally corresponds t o t he eye w it h poorer
mot ilit y. Paresis of t he lat eral or medial rect i can be easily diagnosed using
t hese rules. Vert ical gaze palsies can also be diagnosed in t his manner, t aking
int o account t he act ions, described earlier, of t he eight muscles t hat part icipat e
in vert ical movement and t he f act t hat w it h vert ical deviat ion, t he hypot ropic eye
regist ers t he higher image. The f ollow ing st eps are of t en recommended:
1. Det ermine w hich eye is higher. I f t he right eye is higher (right hypert ropia),
t he right depressors or t he lef t elevat ors are w eak.
2. Have t he pat ient look t o bot h sides. I f t he images now appear f art her apart
on lef t lat eral gaze (right hypert ropia w orse on lef t gaze), eit her t he right SO
or t he lef t SR is w eak.
3. Have t he pat ient look up and dow n t ow ard t he side w here separat ion w as
great er. I f t his maneuver elicit s great er separat ion on dow ngaze, t he right
SO is t he w eak muscle.
These st eps can be supplement ed w it h Bi el schowsky's head-ti l t test, w hich is

usually
posit ive w it h an oblique muscle palsy. Tilt ing t he head t ow ard t he side of a w eak
SO increases t he separat ion of t he images, w hich become single w hen t he head
is t ilt ed opposit e t he side of t he w eak muscle. Normally, a small count er-rolling
of t he eyes occurs w it h a head t ilt ; t his count er-rolling is accomplished by
cont ract ion of t he SR and SO of one eye and by t he I R and I O of t he ot her eye.
When t he act ion of t he SO muscle on one side is lacking, t ilt ing t ow ard t hat side
result s only in SR cont ract ion, w hich elevat es and int ort s t he eye due t o t he
induced ocular count er-rolling. Diplopia caused by a right SO palsy is
compensat ed by a lef t w ard t ilt of t he head. Theref ore, a vert ical muscle palsy
must be suspect ed in pat ient s w it h a head t ilt .
Objective Testing
O bject ive diplopia t est ing is used w hen t he pat ient is uncooperat ive or w hen
t here is misalignment of t he eyes, suggest ing ocular mot or w eakness, but t he
pat ient denies diplopia. This sit uat ion occurs more of t en w it h long-st anding
ocular mot or w eakness or w it h def ect s of visual percept ion. I t may rarely occur
w it h subacut e lesions, how ever, w hen t he image of t he nonf ixat ing eye is
suppressed. I n t his inst ance, t he pat ient may give a hist ory of t ransient diplopia.
The al ternate cover test is perf ormed by having t he pat ient f ixat e on a t arget in
each of t he nine posit ions of gaze. While in each posit ion, t he eyes are observed
f or angular deviat ions f rom t he direct ion of t he t arget as each eye is alt ernat ely
covered (Fig. 8-2). I n a pat ient w it h a right t hird nerve palsy (TNP), bot h eyes
remain parallel on gaze t o t he right , but on lef t lat eral gaze t he uncovered eye is
direct ed t ow ard t he t arget , w hile t he covered eye is at an angle t o it . When t he
right eye is covered and t he lef t eye f ixat es, t he right eye deviat es out w ard
(exophoria), and w hen t he cover is placed over t he lef t eye, t he right eye moves
inw ard (movement of redress) and t he lef t eye moves out w ard. The deviat ion of
t he paret ic eye, t ermed pri mary devi ati on, is smaller t han t he deviat ion of t he
sound eye, called secondary devi ati on. I n t he earlier example of a right TNP, it is
logical t hat , w hen t he eyes look t o t he lef t , t he out w ard deviat ion of t he covered
lef t eye w hen t he right eye f ixat es is great er t han it is w hen t he cover is
sw it ched, because a st rong lef t w ard gaze movement has t o compensat e f or t he
w eakened right MR t o allow t he right eye t o f ixat e. These deviat ions elicit ed by
t he alt ernat e cover t est may be measured w it h prisms, w it h t he prism “point ing”
t ow ard t he deviat ion (e. g. , w it h a hypert ropia, a basedow n prism is placed over
t he aff ect ed eye, w hereas w it h an esodeviat ion, a baseout prism is placed over
t he aff ect ed eye). The f our-st age procedure not ed earlier f or invest igat ing
vert ical deviat ion may incorporat e t he alt ernat e cover t est t o det ermine t he
hypert ropic eye in t he t est direct ions, including head t ilt (t he Bielschow sky head-
t ilt t est ).
FI G URE 8-2 Alt ernat e cover t est in a right medial rect us palsy. A: When t he
right (w eak) eye f ixat es, t he lef t is draw n in t he direct ion of gaze (secondary
deviat ion, D2) and is deviat ed f rom t he orient at ion t o t he t arget (bold line).
B: When t he right eye is covered, t he lef t eye is orient ed t o t he t arget ,
having covered an angle equal t o t he amount of t he secondary deviat ion
(D2). How ever, t he right eye now drif t s t ow ard midposit ion, deviat ing
(primary deviat ion, D1) f rom t he orient at ion t o t he t arget .
The three-step test can be applied w it h t he cover–uncover examinat ion in t he

evaluat ion of vert ical diplopia as f ollow s:
1. Det ermine w het her t here is a right or lef t hypert ropia or hyperphoria in
primary posit ion. For example, if t here is a right hypert ropia in primary
posit ion, t here is paresis of t he right eye depressors (right I R or SO ) or lef t
eye elevat ors (lef t SR or I O ).
2. Compare t he amount of vert ical deviat ion in right and lef t gaze. For example,
if t he right
hypert ropia increases in t he lef t gaze, eit her t he right SO or lef t SR is

underact ing.
3. Compare t he vert ical deviat ion in right -head t ilt and lef t -head t ilt
(Bielschow sky maneuver). For example, if t he vert ical deviat ion increases
w it h right -head t ilt , t he right SO must be w eak; if t he hyperdeviat ion
increases w it h lef t -head t ilt , t he lef t SR is w eak.
Ducti ons (each eye moving separat ely) and versi ons (t he eyes moving
conjugat ely) must alw ays be assessed. I n assessing normal lat eral eye
excursion, an imaginary vert ical line t hrough low er lacrimal punct um should
coincide w it h a boundary line bet w een t he inner t hird and out er t w o-t hirds of
cornea. I f more cornea is hidden, adduct ion is excessive; if more cornea and
some sclera are visible, adduct ion is limit ed. I f abduct ion is normal, t he corneal
limbus should t ouch t he out er cant hus. I f t he limbus passes t hat point and some
of t he cornea is hidden, abduct ion is excessive; if some of t he sclera remains
visible, abduct ion is limit ed [821] .
Pat ient s w it h binocular vert ical diplopia may adopt a compensat ory head, f ace,
or chin posit ion t o move t heir eyes int o a gaze angle t hat achieves binocular
single vision. Underact ion of t he SR or I R muscles is compensat ed by chin
f lexion or ext ension t hat seeks t o avoid t he eye posit ion of maximum image
separat ion. Torsional diplopia is usually caused by underact ion of t he SO or I O
muscles and may be associat ed w it h an angular head t ilt . This head t ilt is
assumed t o avoid t he vert ical and t orsional image separat ion.
O cul ar torsi on may be measured w it h t he double Maddox rod t est , w hich ut ilizes
a red Maddox rod over t he right eye and a w hit e Maddox rod over t he lef t eye in
a t rial f rame. A t hin basedow n prism may be placed bef ore one eye t o separat e
t he horizont al lines induced. The t ilt of t he ret inal image is opposit e t he t ilt of t he
horizont al line, as seen by t he pat ient . Theref ore, w hen t he line is seen slant ed
t ow ard t he nose, an excyclodeviat ion is present w hile if t he t ilt is t ow ard t he
t emple, an incyclodeviat ion is present . A simple mnemonic rule is t hat t he line is
alw ays t ilt ed in t he direct ion in w hich t he off ending muscle w ould rot at e t he eye
if it w ere act ing alone [821] . For example, a pat ient w it h right SO muscle palsy
w ill describe t he red line t o be low er t han t he w hit e line and relat ively int ort ed or
slant ed t ow ard t he nose. The Maddox rod is t hen t urned unt il t he t w o lines are
parallel and t he magnit ude of t he cyclot ropia can be read off t he t rial f rame.
Cyclodeviat ion may also be not ed w it h indirect opht halmoscopy [821] .
Childhood Strabismus
These syndromes are brief ly discussed as t hey may be conf used w it h acquired
causes of esot ropia (ET) and exot ropia (XT) [821] . Most childhood ETs are
comit ant and present at an early age w it h “crossed-eyes” or amblyopia.
Childhood comit ant ETs may be due t o hyperopia or impaired accommodat ion or
convergence. Noncomit ant childhood ETs include A-pat t ern and V-pat t ern
esodeviat ions, in w hich t he esodeviat ion is w orse on upw ard and dow nw ard
gaze, respect ively, ret ract ion syndromes, and mechanical-rest rict ive
esodeviat ion due t o t he congenit al f ibrosis of t he MR muscle. Some pat ient s w it h
congenit al nyst agmus are able t o decrease t he amplit ude or f requency of t heir
nyst agmus by convergence (nyst agmus blockage syndrome) and t hereby an ET
develops.
O ccasionally, adult s w it h a long-st anding, essent ially asympt omat ic, esophoria
may present w it h diplopia due t o “decompensat ion. ” This decompensati on of a
l ong-standi ng esophori a may occur af t er head t rauma, w it h changing ref ract ive
needs, af t er cat aract surgery, w hen t he pat ient receives drugs t hat depress t he
cent ral nervous syst em (e. g. , alcohol or sedat ives), w it h syst emic illnesses, or
f or unclear reason. Hist ory and examinat ion of t en reveal support ive evidence f or
a long-st anding st rabismus, including a hist ory of childhood st rabismus or
pat ching, t he presence of an old head t urn, and horizont al comit ance. Childhood
XT is less f requent t han childhood ET. The XT may be int ermit t ent or persist ent
and somet imes adult s w it h exophoria or int ermit t ent XT may present w it h
diplopia due t o t he inabilit y t o adequat ely compensat e f or t he eye misalignment
(decompensat ion of exophoria).
Decompensat ion of a long-st anding phoria may also cause hypert ropia and
vert ical diplopia [128] . Neuro-opht halmologic hist ory and examinat ion of t en
reveal support ive evidence f or a long-st anding st rabismus including a hist ory of
childhood st rabismus or pat ching, t he presence of a head t ilt or t urn (old
phot os), and large vert ical f usional amplit ude (6 t o 20 prism diopt ers). Verti cal
f usi onal ampl i tudes are measured by present ing vert ically orient ed prisms of
gradually increasing st rengt h in f ront of one eye af t er f irst neut ralizing any
manif est t ropia. The amount of prism needed t o produce diplopia over t hat
needed t o neut ralize t he t ropia (if present ) represent s t he f usional amplit ude
(normal vert ical f usional amplit udes are 2 t o 4 prism diopt ers).
Sensory deviat ions including ET or XT result f rom reduced visual acuit y in one
eye. These pat ient s do not complain of diplopia because of t he visual loss. Loss
of f usion in cases of visual
loss allow s a preexist ing phoria t o become manif est . Sidikaro and von Noorden
report ed 121 pat ient s w it h sensory het erot ropias and not ed t hat ET and XT
occurred w it h almost equal f requency w hen t he onset of visual impairment
occurred at birt h or bet w een birt h and 5 years [714] . Sensory XT, how ever,
predominat es in older children and adult s.
Disease of the Ocular Muscles

Disease of isolat ed ext raocular muscles, part icularly w hen it aff ect s t he lat eral
rect us or t he SO or causes pat t erns of w eakness t hat resemble cent ral
involvement , may be diff icult t o diff erent iat e f rom neurogenic w eakness.
Processes t hat limit t he range of mot ion of t he globe by short ening or f ibrosis of
t he muscles, such as old t rauma or chronic progressive opht halmoplegia, can be
dist inguished f rom neurogenic w eakness because t he f orced duct ion t est ,
described in t he preceding t ext , is normal in neurogenic w eakness.
A mechanical rest rict ion t o t he f ree movement of t he SO t endon at t he pulley
may prevent t he upw ard and inw ard movement of t he globe (Brown's superi or
obl i que tendon sheath syndrome) [821, 839] . Episodic vert ical diplopia is a
result of int ermit t ent t rapping of t he eye on gaze dow nw ard and inw ard or in t he
f ield of act ion of t he SO , t heref ore mimicking paresis of t he I O muscle. This
prevent s t he eye f rom moving upw ard w hile adduct ed, imit at ing an isolat ed I O
muscle palsy. The eye may t hen release suddenly, occasionally associat ed w it h
t he sensat ion or act ual hearing of a click. This syndrome may be due t o sw elling
of t he SO t endon behind t he pulley and may be congenit al or acquired. Acquired
et iologies include superomedial orbit al t rauma, t enosynovit is or myosit is,
adhesions, met ast asis t o t he SO muscle, peribulbar anest hesia, blepharoplast y,
f ront al sinus ost eoma, et hmoid sinus mucocele, pansinusit is, and maxillof acial or
sinus surgery [18, 45, 224, 685, 774] . The superior oblique click syndrome is a
f orm of int ermit t ent acquired Brow n's syndrome w it h a clinical pict ure t hat
alt ernat es bet w een a Brow n's-t ype syndrome and an SO muscle palsy [830] .
Lesions are locat ed w it hin t he sheat h of t he ant erior SO t endon, and include
schw annoma and giant cell t umor of t he t endon.
Thyroi d (G raves') ophthal mopathy is generally preceded by exopht halmos and
orbit al edema [64, 65, 66] . The myopat hy of dyst hyroid orbit opat hy is at t ribut ed
t o inf lammat ion and f ibrosis of t he muscles, sparing t endinous insert ions. The
diplopia is usually due t o a “t ight ” rat her t han a “w eak” muscle. The inf erior rect i
are usually most severely aff ect ed (causing a hypot ropia), f ollow ed by t he
medial rect i, superior rect i, and oblique muscles (t he mnemonic “I'M SO glad I do
not have t hyroid eye disease” is usef ul in remembering t he f requency of muscle
involvement w it h t he “I ” st anding f or t he I R, t he “M” f or t he MR, et c. ). The lat eral
rect us is rarely aff ect ed; t heref ore, t he presence of an exot ropia in a pat ient
w it h t hyroid opht halmopat hy should raise t he possibilit y of concomit ant
myast henia gravis. Vert ical diplopia caused by asymmet ric involvement of t he
inf erior or superior rect i muscles is t he most common present at ion. Diplopia in
t hyroid opht halmopat hy may be w orse in t he morning and bet t er as t he day
progresses [234] . O t her component s of dyst hyroid orbit opat hy include orbit al
congest ion, upper lid ret ract ion, lid lag on looking dow n, propt osis, conjunct ival
inject ion, and opt ic neuropat hy due t o compression of t he opt ic nerve by
enlarged ext raocular muscles in t he orbit al apex [567] . The clinical
manif est at ions of G raves' opht halmopat hy are out lined in Table 8-1 [ 465] .
Myastheni a gravi s should be considered in any case of ocular mot or w eakness
because it can easily mimic neurogenic paresis [828] . Weakness of t he
ext raocular muscles occurs in close t o 90% of pat ient s w it h myast henia gravis at
disease onset , and at least 15% of all pat ient s w it h myast henia gravis w ill
manif est only ocular signs. O f t he 50% t o 80% of pat ient s w it h purely ocular
sympt oms and signs at onset t hat go on t o develop generalized myast henia
gravis, most , but not all, develop generalized sympt oms w it hin 2 t o 3 years of
t he onset of t he disorder [81] . Myast henia gravis should be a diagnost ic
considerat ion in any pat ient w ho present s w it h painless, pupil-sparing, diplopia
or pt osis. Any muscle may be select ively impaired, especially t he MR, and
w eakness charact erist ically increases w it h sust ained eff ort . There is of t en
asymmet ric pt osis t hat becomes more pronounced on sust ained upgaze.
“Enhanced ptosi s” may also be demonst rat ed (i. e. , a w orsening of pt osis on one
side w hen t he opposit e eyelid is elevat ed and held in a f ixed posit ion) [294] , but
t his sign is not specif ic f or myast henia because it may rarely be seen w it h senile
pt osis, ocular myopat hy, Lambert -Eat on myast henic syndrome, Fisher syndrome,
or even TNP [114, 747] . During ref ixat ion f rom dow n t o t he primary posit ion, t he
upper eyelid may bare t he sclera t ransient ly (Cogan's l i d-twi tch si gn). Also, a
“peek sign” may occur: in an at t empt t o sust ain f orcef ul eye closure, t he
orbicularis oculi (O O c) may f at igue, result ing in t he pat ient “peeking” t hrough t he
part ially opened
palpebral f issure. Myast henia can mimic pupil-sparing TNPs, superior division
TNPs, abducens nerve palsies, or t rochlear nerve palsies [189, 529, 598, 732,
828] . Eye movement abnormalit ies due t o myast henia may also mimic
int ernuclear opht halmoplegia [284, 361] , gaze palsy, one-and-a-half syndrome
[ 184] , complet e ext ernal opht halmoplegia, or ot her cent ral lesions [828] . Also,
cert ain int racranial mass lesions (e. g. , parasellar t umors and aneurysms or
midbrain gliomas) may mimic t he w eakness and f at igabilit y of t he lids and
ext raocular muscles seen w it h myast henia gravis [12, 535, 541, 635] . For
example, isolat ed, int ermit t ent unilat eral pt osis w as t he present ing sign on a
pat ient w it h a post erior carot id art ery aneurysm [791] . Besides myast henia
gravis and dyst hyroid orbit opat hy, t he diff erent ial diagnosis of chronic
progressive ext ernal opht halmoplegia (CPEO ) includes oculopharyngeal
dyst rophy, Kearns-Sayre syndrome, myot ubular myopat hy, myot onic dyst rophy,
Bassen-Kornzw eig syndrome (abet alipoprot einemia), Ref sum's syndrome, and
St ephen's syndrome (CPEO , peripheral neuropat hy, and at axia) [480] .
TABLE 8-1 Typical Features of Graves'

Ophthalmopathy
Eyelid signs
Lid retraction (the most common clinical feature of
Graves' ophthalmopathy)
Stare
Lid lag in downgaze
Exophthalmos
Enlargement of extraocular muscles
Increased orbital fat volume
Diplopia/Ophthalmoplegia Secondary to Extraocular
Muscle Inflammation or Fibrosis
Visual loss due to a compressive optic neuropathy
Extraocular muscle involvement in the orbital apex
Stretching of the optic nerve due to proptosis
Severe proptosis and secondary exposure keratopathy
Signs and symptoms of orbital congestion
Because of proptosis with or without venous outflow
obstruction
Conjunctival injection and chemosis
Eyelid and periorbital edema
Tearing, photophobia, and orbital discomfort
From Lee AG, Brazis PW. Clinical pathways in neuro-

ophthalmology. An evidence-based approach, 2nd ed.
New York: Thieme Medical Publishers, 2003.
Botul i sm, like myast henia gravis, aff ect s t he neuromuscular junct ion and can
cause similar eye f indings, usually associat ed w it h blurred vision secondary t o
accommodat ive paresis [716] . The myastheni c (Lambert-Eaton) syndrome may
cause pt osis but seldom causes opht halmoparesis [594] . Acut e opht halmoparesis
may also occur in t he ant i-G Q 1b ant ibody syndrome [497] .
O ccasionally, cert ain disease processes may cause isolat ed paresis of an
individual ext raocular muscle. For example, isolat ed I R paresis may develop w it h
t rauma, mult iple sclerosis, myast henia, or vascular disease and may also occur
on a congenit al or idiopat hic basis [822] .
O rbi tal pseudotumor (i di opathi c orbi tal i nf l ammati on) is a clinicopat hologic
ent it y w it h t he f ollow ing diagnost ic crit eria: (a) a unilat eral orbit al mass lesion,
clinically present ing w it h signs of mass eff ect , inf lammat ion, and/ or inf ilt rat ion,
(b) neuroimaging show ing a f ocal or diff use inf lammat ory lesion, (c)
hist opat hology demonst rat ing a f ibro-inf lammat ory lesion, and (d) invest igat ions
eliminat ing ident if iable local or syst emic causes [10, 453, 538] . When t he
inf lammat ory process is conf ined t o one or mult iple ext raocular muscles, t he
process is ref erred t o as orbi tal myosi ti s, alt hough some aut hors f eel t hat
orbit al pseudot umor and orbit al myosit is may be dist inct clinicot herapeut ic
ent it ies [539] . Pat ient s present w it h acut e or subacut e orbit al pain and diplopia.
Findings include conjunct ival chemosis and inject ion, pt osis, and propt osis. The
process may be unilat eral or bilat eral. The illness is of t en monophasic but
recurrent episodes may occur.
Ocular Motor Nerves and Localization of Lesions

Three brainst em nuclei cont ain t he low er mot or neurons t hat cont rol t he eye
muscles: (a) t he CN I I I (oculomot or) nucleus in t he midbrain, (b) t he CN I V
(t rochlear) nucleus at t he level of t he midbrain–pont ine junct ion, and (c) t he CN
VI (abducens) nucleus in t he low er pons. All are paired st ruct ures locat ed in t he
dorsal part of t he t egment um at t heir respect ive levels. The sixt h nerve
innervat es t he lat eral rect us, and t he f ourt h nerve supplies t he SO . All t he ot her
muscles are innervat ed by t he t hird CN. Muscles innervat ed by neurons on t he
same side (ipsilat eral innervat ion) include t he lat eral (sixt h nerve) and medial
(t hird nerve) rect i, t he I R (t hird nerve), and t he
I O (t hird nerve). The SR (t hird nerve) and t he SO (f ourt h nerve) are innervat ed
by neurons locat ed on t he cont ralat eral side. How ever, t he f ibers t o t he SR
cross at t he level of t he nucleus, so t hat nuclear lesions result in bilat eral
w eakness. Similarly, oculomot or nuclear lesions cause bilat eral pt osis because
t he nuclear group f or t he levat or of t he lid is locat ed in t he midline (a single
caudal subnucleus).
Oculomotor Nerve (Cranial Nerve III)

Anatomy
The t hird nerve nucl ear compl ex ext ends rost rocaudally f or about 5 mm near t he
midline in t he midbrain at t he level of t he superior colliculus (SC) (Figs. 8-3 and
8-4). I t lies vent ral t o t he Sylvian aqueduct , separat ed f rom it by t he
periaqueduct al gray (PAG ) mat t er, and dorsal t o t he t w o medial longit udinal
f asciculi. O ne unpaired and f our paired rost rocaudal columns can be
dist inguished in t he oculomot or nuclear complex. The unpaired column, shared by
t he right and lef t nuclei, is in t he most dorsal locat ion and cont ains t he visceral
nuclei (Edinger-West phal nucleus) rost rally and t he subnucleus f or t he levat or
palpebrae (LP) superioris caudally. The Edinger-West phal nucleus mediat es
pupillary const rict ion. O f t he f our paired subnuclei, t he most medial innervat es
t he SR muscle. This is t he only port ion of t he oculomot or nucleus t hat sends it s
axons t o t he opposit e eye. Decussat ing f ibers act ually t raverse t he cont ralat eral
subnucleus f or t he SR. Hence, a dest ruct ive lesion in one SR subnucleus result s
in bilat eral denervat ion of t he superior rect i. Lat erally in each oculomot or
complex t here are t hree subnuclei: dorsal (I R), int ermediat e (I O ), and vent ral
(MR). Act ually, neurons supplying t he MR are dist ribut ed int o t hree separat e
areas of t he oculomot or nucleus.
FI G URE 8-3 Sagit t al sect ion t hrough t he brainst em show ing st ruct ures t hat
play an import ant role in t he mot or cont rol of eye movement s. III = nucl eus
of cranial nerve I I I ; IV = nucl eus of cranial nerve I V: VI = nucl eus of cranial
nerve VI ; PAG = peri aqueductal gray; SC = superi or colliculus; PC =
posteri or commissure; INC = i ntersti ti al nucleus of Cajal; TR = tractus
ret rof lexus; ri MLF = rostral int erst it ial nucleus of t he medial longit udinal
f asciculus; MB = mammi l l ary bodies; CN III = crani al nerve I I I ; CN VI =
crani al nerve VI ; MLF = medi al longit udinal f asciculus; IO = i nf eri or olive 6;
MT = mammi l l othal ami c f ibers.
I n t he subst ance of t he midbrain (f asci cul ar port ion), t he axons of t he

oculomot or neurons cross t he medial longit udinal f asciculus (MLF) and t he
decussat ing f ibers of t he superior cerebellar peduncle and t hen diverge w idely
as t hey t raverse t he red nucleus bef ore exit ing on t he
ant erior aspect of t he midbrain just medial t o t he cerebral peduncles. Fibers f or

t he elevat ors of t he eye and eyelid are probably locat ed lat erally in t he
f ascicular port ion of t he oculomot or nerve. I n t he subarachnoi d space each t hird
nerve passes bet w een t he superior cerebellar and t he post erior cerebral
art eries, courses f orw ard near t he medial aspect of t he uncus of t he t emporal
lobe, pierces t he dura just lat eral t o t he post erior clinoid process, and ent ers t he
lat eral w all of t he cavernous si nus ( Fig. 8-5; see also Fig. 7-4). Here, t he nerve
runs over t he t rochlear nerve, lying superior t o t he abducens nerve and medial t o
t he opht halmic branch of t he t rigeminal nerve. O nce it reaches t he superi or
orbi tal f i ssure, t he oculomot or nerve divides int o a superior division, w hich
supplies t he SR and t he LP superioris, and an inf erior division, w hich supplies
t he medial and inf erior rect i, t he I O , and t he presynapt ic parasympat het ic
out f low t o t he ciliary ganglion (sphinct er pupillae muscle and ciliary muscles).
This division int o superior and inf erior rami may also t ake place w it hin t he
ant erior cavernous sinus or post erior orbit , and, indeed, more proximally, even at
a f ascicular level.
FI G URE 8-4 The oculomot or nerve. Cross sect ion of upper midbrain w it h
nucleus and course and dist ribut ion of axons t o t he eye. (From Daube JR,
Regan TJ, Sandok BA, et al. Medi cal neurosci ences: an approach to
anatomy, pathol ogy, and physi ol ogy by system and l evel s, 2nd ed. Bost on,
MA: Lit t le, Brow n and Company, 1986. By permission of Mayo Foundat ion. )
Localization of Lesions
Lesions can aff ect t he t hird nerve in t he brainst em (nucleus or f ascicular
port ion), in t he subarachnoid space, in t he cavernous sinus, at t he superior
orbit al f issure, or in t he orbit [113, 465, 467 ( Table 8-2).
Pure unilat eral nucl ear l esi ons are very rare. Paresis of an isolat ed muscle
innervat ed by t he oculomot or nerve almost alw ays result s f rom lesions in t he
orbit or f rom muscle disease. How ever, nuclear lesions may give rise t o isolat ed
w eakness of one of t he muscles innervat ed by t he oculomot or nerve (e. g. , t he
I R) w it h t he except ion of t he f ollow ing muscles: SR, LP superioris, and
const rict or of t he pupil [75, 90, 152, 628, 759] . These muscles w ould be
aff ect ed bilat erally even w it h small nuclear lesions. As MR neurons probably lie
at t hree diff erent locat ions w it hin t he oculomot or nucleus, it is unlikely t hat MR
paralysis (unilat eral or bilat eral) w ould be t he sole manif est at ion of a nuclear
lesion [798] . More charact erist ic of nuclear involvement is unilat eral TNP,
w eakness of t he ipsilat eral and cont ralat eral SR, and bilat eral incomplet e pt osis
[ 14, 439, 625] . Rarely, t he ipsilat eral SR is spared w hile
t he cont ralat eral SR is paret ic if t he cont ralat eral midbrain lesion select ively
involves crossing SR nerve f ibers. [187, 452] . Bilat eral TNPs w it h sparing of t he
lid levat ors may also be caused by nuclear lesions (t he cent ral caudal levat or
subnucleus is spared) [127, 420] . As cort icof ugal and colliculof ugal
(supranuclear) pat hw ays f or t he cont rol of horizont al saccades t ravel in t he
mesencephalic t egment um near t he oculomot or nucleus (see subsequent t ext ),
unilat eral inf arct ion of t he midbrain–diencephalic junct ion may cause an
ipsilat eral oculomot or nuclear lesion associat ed w it h palsy of cont ralat eral
horizont al saccades [512] . Rarely, isolat ed bilat eral pt osis w it h sparing of t he
ext raocular muscles and pupils may occur w it h lesions involving t he levat or
subnucleus and sparing more rost ral oculomot or subnuclei [166, 305, 511] . Af t er
surgery f or a f ourt h vent ricle ependymoma, bilat eral nuclear oculomot or palsies
aff ect ing only t he levat or and superior rect i subnuclei have been described,
result ing in t hird nerve paresis aff ect ing only t he levat ors and superior rect i
bilat erally [681] . Nuclear lesions aff ect ing t he pupil indicat e dorsal, rost ral
damage and are of t en associat ed w it h supranuclear or nuclear vert ical gaze
palsies.
FI G URE 8-5 Coronal diagram of t he cavernous sinus. V1 = opht halmic
division of cranial nerve V; V2 = maxillary division of cranial nerve V; V3 =
mandibular division of cranial nerve V.
Alt hough isolat ed I R paresis may occur because of damage of t he I R

subnucleus, a lesion just rost ral t o t he t hird nerve nucleus select ively damaging
t he supranuclear descending pat hw ay f rom t he rost ral int erst it ial nucleus of t he
medial longit udinal f asciculus (riMLF) t o t he I R subnucleus may also cause an
isolat ed I R palsy [759] .
Bilat eral t ot al opht halmoplegia, bilat eral complet e pt osis, and large, unreact ive
pupils have been described w it h midbrain hemat oma [845] . This const ellat ion of
f indings w as t hought t o be due t o bilat eral t hird nerve nuclear or f ascicular
damage or bot h, bilat eral involvement of t he int erst it ial nucleus of Cajal (I NC)
and t he riMLF, and t he involvement of bilat eral horizont al saccadic and smoot h
pursuit pat hw ays (see subsequent t ext ).
Fasci cul ar l esi ons of t en accompany nuclear lesions because inf arct ion is a
common cause of nuclear TNP, and t he paramedian branches near t he t op of t he
basilar art ery of t en f eed bot h st ruct ures. For example, inf arct ion of t he dorsal,
paramedian midbrain may cause bilat eral pt osis associat ed w it h unilat eral
paresis of all ot her muscles innervat ed by t he oculomot or nerve (pupil spared)
w it h sparing of t he cont ralat eral SR muscle [493] . These unique f indings suggest
a lesion of t he proximal t hird nerve f ascicles and t he cent ral caudal subnucleus.
Third nerve f ascicular lesions are most of t en caused by inf arct ion, hemorrhage,
or demyelinat ion. Pure f ascicular lesions cause a peripheral t ype of oculomot or
palsy t hat is associat ed bot h w it h ipsilat eral involvement of all t he
muscles innervat ed by it and w it h sparing of t he ot her eye. Furt hermore,

involvement of brainst em st ruct ures ot her t han t he f ascicles of t he t hird nerve
helps t o ident if y t he ext ent and t he locat ion of t he lesion. For example,
ipsilat eral TNP and cont ralat eral dow nbeat nyst agmus (DBN) (see subsequent
t ext ) may be caused by unilat eral paramedian t halamopeduncular inf arct ion
[ 591] . Fascicular involvement and concomit ant damage of t he red nucleus and
superior cerebellar peduncle causes cont ralat eral at axia and out f low t ract
cerebellar t remor (Cl aude's syndrome) [28, 495] . A more ant erior lesion,
aff ect ing t he peduncle and oculomot or f ascicle, gives rise t o oculomot or palsy
w it h cont ralat eral
hemiparesis (Weber's syndrome). The TNP w it h Weber's syndrome may aff ect or
spare t he pupillary f ibers [675] . Larger lesions t hat aff ect t he oculomot or
f ascicle and t he red nucleus–subst ant ia nigra region may produce oculomot or
palsy w it h cont ralat eral choreif orm movement s or t remor (Benedi kt's syndrome)
[ 98] , somet imes associat ed w it h cont ralat eral hemiparesis if t he cerebral
peduncle is also involved [495] . Alt hough pupillary displacement (corect opia),
oval pupils, and irregularit y of t he pupils are occasionally f ound w it h peripheral
t hird nerve lesions and are of t en due t o f ocal pat hology in t he iris, t hey
f requent ly result f rom midbrain lesions (“mi dbrai n corectopi a”) [700] .
TABLE 8-2 The Localization of Oculomotor Nerve

Lesions
Structure
Clinical Manifestation
Involved
Lesions affecting the third nerve nucleus
Ipsilateral complete CN III palsy;

Oculomotor
contralateral ptosis and superior
nucleus
rectus paresis
Oculomotor Isolated muscle palsy (e.g.,

subnucleus inferior rectus)
Isolated levator
Isolated bilateral ptosis
subnucleus
Lesions affecting the third nerve fasciculus
Partial or complete isolated CN III

Isolated fascicle palsy with or without pupil
involvement
Plus-minus syndrome (ipsilateral

Paramedian
ptosis and contralateral eyelid
mesencephalon
retraction)
Fascicle, red
nucleus, superior Ipsilateral CN III palsy with
cerebellar contralateral ataxia and tremor
peduncle (Claude)
Ipsilateral CN III palsy with

Fascicle and
contralateral hemiparesis
cerebral peduncle
(W eber's)
Fascicle and red Ipsilateral CN III palsy with

nucleus/substantia contralateral choreiform
nigra movements (Benedikt)
Lesions affecting the third nerve in the subarachnoid

space
Complete CN III palsy with or

Oculomotor nerve without other CN involvement;
superior or inferior division palsy
Lesions affecting the third nerve in the cavernous sinus
Painful or painless CN III palsy;

with or without palsies of CN IV,
Cavernous sinus
VI, and V1; CN III palsy with small
lesion
pupil (Horner syndrome); primary
aberrant CN III regeneration
Lesions affecting the third nerve in the superior orbital

fissure
CN III palsy with or without

Superior orbital palsies of CN IV, VI, V1; often
fissure lesion with proptosis
Lesion affecting the third nerve in the orbit
Oculomotor nerve;
CN III palsy; superior or inferior
superior or branch
CN III branch palsy
lesion
Optic nerve; Visual loss; proptosis; swelling of

orbital structures lids; chemosis
CN = cranial nerve.
Rarely, a unilat eral or bilat eral f ascicular t hird nerve lesion may occur in isolat ion
w it hout ot her ocular mot or or neurologic signs or sympt oms [2, 21, 57, 90, 239,
282, 408, 427, 571, 657, 769, 797] . Fascicular lesions, even w hen bilat eral, may
occasionally spare pupillary f unct ion [836] , and bilat eral preganglionic int ernal
opht halmoplegia (dilat ed nonreact ive pupils) w it hout mot or involvement has been
described w it h bilat eral part ial oculomot or f ascicular lesions [332] . Because of
t he int ra-axial t opographic arrangement of f ibers, f ascicular lesions may cause
TNPs limit ed t o specif ic oculomot or-innervat ed muscles [449, 798] . For example,
f ascicular lesions have result ed in (a) isolat ed I O paresis [142] , (b) a unilat eral
f ixed, dilat ed pupil unassociat ed w it h ot her neurologic dysf unct ion [712] , (c)
paresis of t he SR and I O w it hout ot her evidence of oculomot or nerve involvement
[ 153, 273] , (d) paresis of t he SR and MR [675] , (e) paresis of t he levat or
muscle, SR and MR [595] , (f ) paresis of t he I O , SR, MR, and levat or muscle
w it h sparing of t he I R muscle and pupil [565, 697, 711] , (g) paresis of t he I O ,
SR, MR, levat or, and I R w it h pupillary sparing [119, 351, 565] , and (h) paresis
of t he lef t I R, lef t pupil, right SR, convergence, and lef t MR [798] . O n t he basis
of t hese clinical st udies, it has been proposed t hat individual t hird nerve
f ascicles in t he vent ral mesencephalon are arranged t opographically f rom lat eral
t o medial as f ollow s: I O , SR, MR and LP, I R, and pupillary f ibers (Fig. 8-6)
[ 142] . A rost ral-caudal t opographic arrangement has also been suggest ed w it h
pupillary f ibers most superior, f ollow ed by f ibers t o t he I R, I O , MR, SR, and
levat or, in t hat order [675, 697, 798] . This model also serves t he descript ion of a
“superior division” oculomot or palsies (i. e. , paresis of t he SR and levat or
muscles w it hout involvement of ot her groups) [306, 355, 448 and an “inf erior
division” oculomot or palsies (paresis of I R, I O , MR, and pupillary f ibers w it h
sparing of t he SR and levat or) [2, 222, 448 associat ed w it h int raaxial midbrain
lesions. Theref ore, alt hough superior and inf erior divisional TNPs have classically
been localized t o ant erior cavernous sinus or post erior orbit al lesions, such
report s suggest t hat a divisional t hird nerve pat t ern may occur f rom damage at
any locat ion along t he course of t he oculomot or nerve, f rom t he f ascicle t o t he
orbit [448] .
Fascicular or nuclear TNPs may occasionally be associat ed w it h ipsilat eral
pt osis and cont ralat eral eyelid ret ract ion (pl us-mi nus l i d syndrome) [275, 814] .
This syndrome occurs w it h a small lesion locat ed in t he paramedian
mesencephalon, involving t he ipsilat eral LP f ascicles
as t hey emerge f rom t he cent ral caudal nucleus (CCN) (t he CCN is spared), and
t he inhibit ory pat hw ays project ing on t he LP mot or neurons immediat ely bef ore
t hey ent er int o t he CCN. The plus-minus syndrome has been described w it h
bilat eral glioma ext ending t o t he paramedian midbrain and t halamic–
mesencephalic inf arct ion; it may also occur w it h peripheral processes such as
peripheral TNP, myast henia gravis, orbit al myosit is, congenit al pt osis, or orbit al
t rauma.
FI G URE 8-6 Schemat ic diagram of midbrain at level of SC. Proposed model

of oculomot or f ascicular organizat ion in vent ral midbrain t egment um f rom
lat eral t o medial is as f ollow s: I O f ascicles, SR f ascicles, MR f ascicles, LP
(lid) f ascicles, I R f ascicles, and, most medially, pupillary f ibers (pupil).
(From Cast ro O , Johnson LN, Mamourian AC. I solat ed inf erior oblique
paresis f rom brainst em inf arct ion. Perspect ive on oculomot or f ascicular
organizat ion in t he vent ral midbrain t egment um. Arch Neurol 1990; 47: 235–
237. Copyright 1990, American Medical Associat ion. Reprint ed w it h
permission. )
Celebisoy, et al. described a pat ient w ho present ed w it h t he acut e onset of

part ial oculomot or paresis on one side and upper eyelid ret ract ion on t he ot her
due t o a vascular insult [144] . An elect romyographic (EMG ) st udy revealed
f ront alis muscle overact ivit y on t he side of lid ret ract ion, indicat ing t hat not only
w as t he supramot or cont rol over t he CCN aff ect ed, but t he inhibit ion of t he
f ront alis muscle mot oneurons w as also disrupt ed. O n t he basis of t hese dat a, a
premot oneuronal syst em w as proposed t hat cont rols upper eyelid movement s by
aff ect ing t he f ront alis muscle and O O c muscle mot oneurons in addit ion t o t he
CCN.
An isolat ed peripheral TNP is most of t en relat ed t o an ischemic neuropat hy or t o
a lesion in it s subarachnoi d porti on. Among t hese, compression by int ernal
carot id-post erior communicat ing art ery aneurysms is common. Wit h ischemic
lesions, t he pupil is spared because t he lesion is conf ined t o t he core of t he
nerve and spares peripherally sit uat ed pupillomot or f ibers. Most pat ient s w it h
ischemic oculomot or palsies have complet e resolut ion w it hin 3 t o 6 mont hs of t he
onset of sympt oms [137] . By cont rast , compression of t he t hird nerve by
aneurysm charact erist ically causes dilat at ion and unresponsiveness of t he pupil.
Compressive subarachnoid lesions may occasionally spare t he pupil, how ever,
perhaps due t o t he pressure of t he lesion being evenly dist ribut ed and allow ing
t he relat ively pressure-resist ant , smaller-caliber pupillomot or f ibers t o escape
injury or due t o t he lesion compressing only t he inf erior port ion of t he nerve,
t heref ore sparing t he dorsally sit uat ed pupillomot or f ibers [436, 561] . Wit h
unrupt ured cerebral aneurysms, oculomot or paresis may be incomplet e w it h at
least one element of nerve dysf unct ion (i. e. , pt osis, mydriasis, or ext raocular
muscle w eakness) absent [63] . I nt ermit t ent , isolat ed pt osis has been described
as t he init ial manif est at ion of a post erior carot id art ery aneurysm [791] . Absence
of an aff ect ed pupil in t he set t ing of a compl ete mot or oculomot or paresis almost
alw ays excludes a diagnosis of aneurysm. A pat ient has been described,
how ever, in w hom a painless, pupil-sparing, but ot herw ise complet e oculomot or
paresis w as t he only sign of an aneurysm arising f rom t he basilar art ery [505] .
An isolat ed pupillary paralysis w it hout pt osis or opht halmoparesis is almost
never caused by an aneurysm.
An oculomot or nerve palsy w it h a normal pupillary sphinct er and complet ely
palsied ext raocular muscles and levat or is almost never due t o int racranial
aneurysms. This t ype of TNP is most commonly caused by ischemia, especially
associat ed w it h diabet es mellit us [646] . I schemic oculomot or nerve palsy may
also occur w it h giant cell art erit is [78, 96, 183, 646, 647 and syst emic lupus
eryt hemat osus [663] . I schemic lesions of t he oculomot or nerve of t en spare t he
pupil because t he lesion is conf ined t o t he core of t he nerve and does not aff ect
peripherally sit uat ed pupillomot or f ibers. The pupil may, how ever, be involved in
diabet ic oculomot or palsies [562] and diabet es may even cause a superior
branch palsy of t he oculomot or nerve [515] . I n a prospect ive st udy of 26
consecut ive pat ient s w it h diabet es-associat ed TNPs, int ernal opht halmoplegia
(pupillary involvement ) occurred in 10 pat ient s (38%) [367] . The size of
anisocoria w as 1 mm or less in most pat ient s. O nly t w o pat ient s had anisocoria
>2. 0 mm and it w as never >2. 5 mm. No pat ient had a f ully dilat ed unreact ive
pupil. The aut hor concluded t hat pupil involvement in pat ient s w it h diabet es-
associat ed TNP occurs more of t en t han has previously been recognized
(14%-32% in ot her st udies), alt hough t he degree of anisocoria in any pat ient is
usually 1 mm or less. When comment ing on t his st udy, Trobe st at ed “w e can
presume t hat all pat ient s w ho have oculomot or nerve palsies w it h anisocoria of
>2. 0 mm are out liers f or t he diagnosis of ischemia” [788] . Shih et al. not ed t hat
28. 6% of pat ient s w it h diabet ic ischemic TNP had pupil involvement [707] .
Pat ient s w it h TNP w it h a normal pupillary sphinct er and complet ely palsied
ext raocular muscles should be observed at 24- t o 48-hour int ervals during t he
f irst w eek because some pat ient s w it h aneurysms may develop delayed pupil
involvement [436] . Pat ient s w it h isolat ed incomplet e mot or TNP w it h pupillary
sparing (“relat ive pupil-sparing”) may have a mass lesion or aneurysm [368,
370] . Pat ient s w it h an isolat ed acquired TNP w it h a subnormal pupillary sphinct er
and part ial or complet e ext raocular muscle palsies and pat ient s w it h complet e
ext ernal and int ernal TNPs occurring in isolat ion of t en harbor a compressive
lesion (e. g. , aneurysm) or meningeal inf ilt rat ion [98, 451] .
Spont aneous resolut ion of aneurysmal TNP may rarely occur. Foroozan et al.
described a pat ient w it h a TNP t hat developed in t he t hird
t rimest er of pregnancy and w as due t o a post erior communicat ing art ery
aneurysm [244] . Prepart um complicat ions f orced post ponement of surgery. The
palsy spont aneously resolved over 3 w eeks af t er delivery by C-sect ion.
Repeat ed angiogram show ed t hat t he aneurysmal sac had shrunk f rom 10 t o 4. 5
mm.
Superior division or inf erior division oculomot or paresis may occur w it h
subarachnoid lesions [309] . For example, superior division paresis has been
described w it h a superior cerebellar–post erior cerebral art ery junct ion aneurysm
t hat compressed and f lat t ened t he int erpeduncular oculomot or nerve f rom below
[ 306] , w hile isolat ed inf erior division involvement has occurred w it h t rauma,
vasculit ic or demyelinat ing disease, parasellar t umors (e. g. , meningioma,
schw annoma) [139, 177] , or basilar art ery aneurysm [397] . I nf erior division
involvement w it h t umors may be pupil-sparing, perhaps because insidious t umor
grow t h may spare pressure-resist ant pupillomot or f ibers. Monocular elevat or
paresis f rom isolat ed SR and/ or I O dysf unct ion, is a common neuro-opht halmic
f inding in pat ient s w it h neurof ibromat osis t ype 2 and is probably a sign of t hird
nerve inf ilt rat ion or compression by a schw annoma [217] .
The t hird nerve in it s subarachnoid course may also be damaged by ect at ic
vessels, t umors (part icularly meningiomas, met ast ases, and chordomas),
inf ect ious and inf lammat ory processes of t he meninges, t rauma [339, 698] ,
st ret ching during neurosurgical procedures, or in t he G uillain-Barré syndrome.
Elongat ion of t he nerve by a herniat ed uncus causes, f irst , pupillary dilat at ion
(Hutchi nson pupi l), associat ed w it h poor response t o light but relat ively
preserved convergence, f ollow ed by w eakness of t he ext raocular muscles w hen
t he pupil becomes f ixed. Midbrain corect opia may also occur during
t ranst ent orial herniat ion. Enhancement and t hickening of t he int erpeduncular
segment of t he oculomot or nerve has been not ed on magnet ic resonance imaging
(MRI ) of some children w it h opht halmoplegic migraine [582] . Episodic and
recurrent pupil-involving TNPs have been described w it h crypt ococcal meningit is
[ 41] .
I n t he cavernous si nus see Figure 8-5, compressive lesions of t en also involve
t he ot her ocular mot or nerves and t he opht halmic branch of t he t rigeminal nerve
[ 415] . Combined oculomot or paresis and sympat het ic denervat ion are virt ually
pat hognomonic of a cavernous sinus lesion. Compressive cavernous sinus lesions
may also spare t he pupil because t hey of t en pref erent ially involve only t he
superior division of t he oculomot or nerve, w hich carries no pupillomot or f ibers,
or t he superior aspect of t he nerve ant erior t o t he point w here t he pupillomot or
f ibers descend in t heir course near t he I O muscle. The pupillary “sparing” w it h
ant erior cavernous sinus lesions may be more apparent t han real, result ing f rom
simult aneous injury of nerve f ibers t o bot h t he pupillary sphinct er and dilat or,
result ing in a midposit ion, f ixed pupil [436] . A pat ient w it h a pupil-sparing
“severe” mot or TNP has been described w it h a cavernous sinus aneurysm [358] .
Wit h chronic lesions, aberrant regenerat ion (see subsequent t ext ) may result in
apparent pupillary sparing. Lesions in t he neighborhood of t he post erior clinoid
process may f or some t ime aff ect only t he t hird nerve as it pierces t he dura
(e. g. , breast or prost at ic carcinoma) [176] .
Sensory f ibers f rom t he opht halmic division of t he f if t h CN join t he oculomot or
nerve w it hin t he lat eral w all of t he cavernous sinus [458] . The f ront al-orbit al pain
experienced by pat ient s w it h enlarging aneurysms could t heref ore be caused by
direct irrit at ion of t he t hird nerve [458] . I schemic damage t o t he t rigeminal f ibers
in t he oculomot or nerve may also be t he source of pain in ischemic-diabet ic
TNPs [99] .
Medial lesions in t he cavernous sinus, such as a carot id art ery aneurysm, may
aff ect only t he ocular mot or nerves but spare t he more lat erally locat ed
opht halmic branch of t he t rigeminal nerve, result ing in painless opht halmoplegia.
O n t he cont rary, lesions t hat begin lat erally present w it h ret ro-orbit al pain f irst ,
and opht halmoparesis supervenes only lat er. A TNP may be t he present ing or
sole sign of a pit uit ary adenoma [684] or dural carot id-cavernous sinus f ist ula
[ 338] . Pit uit ary apoplexy causes an oculomot or nerve def icit most of t en and
involves t he abducens nerve and t he t rochlear nerve w it h less f requency [702] .
O ccasionally, pit uit ary apoplexy may present as a pai nf ul TNP [656] . I n
immunosuppressed individuals, cavernous sinus inf ect ion w it h mucormycosis
[ 235] or aspergillosis [214] may develop. The clinical f indings and et iologies f or
processes locat ed in t he superi or orbi tal f i ssure are similar t o t hose of t he
cavernous sinus syndrome.
Lesions w it hin t he orbi t t hat produce t hird nerve dysf unct ion usually produce
ot her ocular mot or dysf unct ion as w ell as opt ic neuropat hy and propt osis (see
Chapt er 7). Wit h space-occupying lesions, how ever, propt osis is a st rong
indicat ion of an orbit al locat ion. When evaluat ing a pat ient w it h an oculomot or
palsy f or propt osis, it must be remembered t hat f laccidit y of t he muscles may
result in propt osis of up t o 3 mm on t he paret ic side. Many lesions ext end f rom
t he cavernous sinus t o t he orbit al apex and vice versa so t hat a clear
separat ion bet w een t he t w o syndromes may be impossible. I solat ed involvement

of t he muscles innervat ed by eit her t he superi or or t he i nf eri or ocul omotor
branch has classically been localized t o an orbi tal process, of t en t rauma or
t umor, or a sphenocavernous lesion [150, 735] . How ever, as not ed earlier, t he
f unct ional division of t he oculomot or nerve is present probably even at t he
f ascicular level, and a divisional pat t ern may occur f rom damage anyw here along
t he course of t he nerve [448] . Superior division or inf erior division t hird nerve
paresis may occur w it h subarachnoid lesions.
Even opht halmoplegic migraine may cause recurrent paroxysmal superior division
oculomot or palsy [400] . Rarely, part ial or complet e oculomot or palsy may f ollow
dent al anest hesia, presumably due t o inadvert ent inject ion of an anest het ic agent
int o t he inf erior dent al art ery or superior alveolar art ery w it h subsequent
ret rograde f low int o t he maxillary, middle meningeal, and f inally t he lacrimal
branch of t he opht halmic art ery [607] .
Congeni tal TNP is rare, usually unilat eral, and may occur in isolat ion or in
associat ion w it h ot her neurologic and syst emic abnormalit ies, including
congenit al f acial nerve palsies or ot her cranial neuropat hies, f acial capillary
hemangioma, cerebellar hypoplasia, gaze palsy, ipsilat eral nevus sebaceous of
Jadassohn, ment al ret ardat ion, digit al anomalies, and sept o-opt ic dysplasia
(opt ic hypoplasia, midbrain malf ormat ions, and hypot halamohypophyseal
dysf unct ion) [46, 320, 359, 457, 601, 625, 695, 831] . All pat ient s have some
degree of pt osis and opht halmoplegia, and nearly all have pupillary involvement .
I n most cases, t he pupil is miot ic rat her t han dilat ed, probably because of
aberrant t hird nerve regenerat ion (see subsequent t ext ), and usually t race
react ive or nonreact ive t o light . Rarely t he pupil may be spared [46] .
Mont hs t o years af t er t he occurrence of an oculomot or lesion, clinical f indings of
aberrant regenerati on of the thi rd nerve may be seen. They include elevat ion of
t he lid on dow nw ard gaze (pseudo-von G raef e phenomenon) or on adduct ion, but
lid depression during abduct ion. The lid-gaze synkinesis is best seen w it h
at t empt ed adduct ion in dow ngaze. This horizont al gaze-lid synkinesis is similar t o
but of opposit e direct ion f rom t he lid synkinesis observed in Duane's ret ract ion
syndrome (see subsequent t ext ). O t her f indings w it h aberrant regenerat ion
include limit at ion of elevat ion and depression of t he eye w it h occasional eyeball
ret ract ion on at t empt ed vert ical gaze, adduct ion of t he eye on at t empt ed
elevat ion or depression, and suppression of t he vert ical phase of t he opt ico-
kinet ic response. The pupil may be in a miot ic or middilat ed posit ion; it may be
f ixed t o light but may respond t o accommodat ion (near-light dissociat ion) or
const rict on adduct ion or dow ngaze. Aberrant regenerat ion t o t he iris sphinct er
may be t oo w eak t o const rict t he pupil on exposure t o light , but at t he slit lamp,
clear segment al cont ract ion of t he sphinct er may be seen w hen t he eye t ries t o
move in any t hird nerve direct ion (Czarnecki 's si gn) [173] . This gaze-evoked
segment al const rict ion of t he pupil may occur in port ions of t he sphinct er t hat
are unreact ive t o light , w hile ot her segment s of t he pupil have normal light
react ion w it hout Czarnecki's sign [174] . Aberrant regenerat ion may be
associat ed w it h lagopht halmos, presumably caused by co-cont ract ion of t he
levat or and SR muscles during Bell's phenomenon [179] .
Aberrant regenerat ion may be seen af t er oculomot or damage due t o congenit al
causes, t rauma, aneurysm, migraine, and syphilis but is almost never caused by
ischemic neuropat hy [61] . A single case of aberrant regenerat ion has been
described because of an ischemic st roke involving t he t hird nerve f ascicle in t he
cerebral peduncle [525] . The misdirect ion of regenerat ing nerve f ibers is t he
likely cause, but it has also been post ulat ed t hat t he syndrome may be due t o
ephapt ic neuron t ransmission of impulses or f rom chromat olysis-induced
reorganizat ion of oculomot or nuclear synapses. Ephapt ic t ransmission w ould
explain t he transi ent oculomot or misdirect ion described w it h opht halmoplegic
migraine, pit uit ary apoplexy, giant cell art erit is, and non-Hodgkin's lymphoma
[ 470] . Long-st anding lesions w it hin t he cavernous sinus, such as meningiomas,
t rigeminal neuromas, pit uit ary t umors, or large aneurysms, may present as a
pri mary aberrant regenerati on of t he t hird nerve w it hout a hist ory of previous
TNP [456] . Primary aberrant regenerat ion may rarely occur w it h ext racavernous
lesions [383, 806] and has even been described w it h a post erior communicat ing
art ery aneurysm [140] . Bilat eral primary aberrant regenerat ion may also occur
w it h abet alipoprot einemia (Bassen-Kornzw eig syndrome) [161] . Rarely, t he
pseudo-von G raef e phenomenon may develop contral ateral t o a regenerat ing
paret ic t hird nerve [308] . Also, combined oculomot or-abducens synkinesis has
been described af t er severe head t rauma, result ing in misdirect ion of nerve
f ibers t o t he right MR and right lat eral rect us [599] .
O cul omotor paresi s wi th cycl i c spasms has been described in w hich pt osis,
mydriasis,
opht halmoparesis, and decreased accommodat ion are cyclically int errupt ed by
t ransient eyelid elevat ion, globe adduct ion, pupil const rict ion, and increased
accommodat ion [250] . This cyclic spasm last s 10 t o 30 seconds and is usually
congenit al but has been not ed w it h brainst em glioma. Miller and Lee described
t w o pat ient s w it h a hist ory of previous skull base irradiat ion f or int racranial
t umor w ho developed acquired oculomot or nerve paresis w it h cyclic spasms
years lat er [532] . Bot h pat ient s developed unilat eral lid ret ract ion and ipsilat eral
ET w it h limit at ion of abduct ion during t he spast ic phase of t he cycle, w it h
ipsilat eral pt osis, XT, and variable limit at ion of adduct ion during t he paret ic
phase. The cycles w ere cont inuous and w ere not induced or alt ered by eccent ric
gaze.
TABLE 8-3 Etiologies of Third Nerve Palsies by
Topographical Localization
Nuclear TNP
Infarction or hemorrhage
Cavernous malformation
Tumor
Infection
Trauma
Multiple sclerosis
Fascicular TNP
Infarction or hemorrhage
“Migraine” with MRI signal abnormalities during acute
phase consisting of a thickening and enhancement of
the nerve at its exit from the midbrain
Tumor
Multiple sclerosis
Stereotactic surgery
Subarachnoid space
Aneurysms of the internal carotid, internal carotid-
posterior communicating, superior cerebellar, basilar,
or posterior cerebral arteries
Ectatic vessels
Middle cerebral artery arteriovenous fistula
Tumors, especially meningiomas, chordomas,
metastases, or primary tumors of the third nerve
Glioblastoma multiforme
Infectious or inflammatory processes of the meninges
(e.g., sarcoidosis and W egener's) and carcinomatous
or lymphomatous meningitis
Recurrent parainfectious third nerve palsy with
cisternal nerve enhancement on MRI
Ophthalmoplegic migraine
Subarachnoid hemorrhage with leukemia
Pseudotumor cerebri
Spontaneous intracranial hypotension
Trauma, especially during neurosurgical procedures
Nerve infarction from diabetes, atherosclerosis, giant
cell arteritis, or systemic lupus erythematosus (nerve
infarction may also occur in the cavernous sinus or
anywhere along the course of nerve)
Uncal herniation
Hydrocephalus
Cavernous sinus/superior orbital fissure

Aneurysm of the internal carotid or posterior
communicating artery
Dural carotid-cavernous sinus fistula
Balloon test occlusion of the cervical internal carotid
artery
Cavernous sinus thrombosis or infection (e.g.,
tuberculoma); superior ophthalmic vein thrombosis
Tumors, including pituitary adenoma, meningioma,
esthesioneuroblastoma, arachnoid cyst, neurinoma,
nasopharyngeal carcinoma, myeloma, lymphoma,
Hodgkin's disease, and metastases
Pituitary infarction or hemorrhage (pituitary apoplexy)
Gammopathy
Intraneural hemorrhage
Mucocele of the sphenoid sinus or sphenoid sinusitis
Tolosa-Hunt syndrome or other granulomatous diseases
Orbit
Infections, inflammations, and granulomatous
processes (e.g., orbital pseudotumor)
Sphenoid sinus mucocele
Tumors
Dural arteriovenous malformation
Trauma
Unknown localization
Congenital
Migraine
Trauma
Viral infections (including herpes zoster ophthalmicus,
Ramsay Hunt syndrome, and cervical zoster) and
immunizations
Lyme disease
Diffuse neuropathic processes (e.g., Fisher syndrome
and chronic inflammatory polyradiculoneuropathy)
Cervical carotid artery dissection, stenosis, or
occlusion
Subdural hematomas
Toxic effects of drugs
Cocaine
Sildenafil citrate (Viagra)
Infliximab
Internal carotid cisplatin infusion (inferolateral trunk
carotid artery neurovascular toxicity)
Dental anesthesia
Scorpion bite
Radiation therapy
Elevated anti-galactocerebroside and anti-GM1
antibodies
Autoimmune associated with anti-GQ1b IgG antibody
[357]
TNP = third nerve palsy; MRI = magnetic resonance
imaging.
neuro-ophthalmology. An evidence-based approach,
2nd ed. New York: Thieme Medical Publishers, 2003.
O phthal mopl egi c mi grai ne usually st art s in t he f irst decade of lif e and usually
aff ect s t he oculomot or nerve, alt hough rare t rochlear nerve or mult iple ocular
mot or nerve involvement has been described [530] . Clinical crit eria essent ial f or
t he diagnosis of opht halmoplegic migraine include (a) a hist ory of t ypical
migraine headache (severe, t hrobbing, unilat eral but occasionally bilat eral or
alt ernat ing); t he headache may last hours t o days; (b) opht halmoplegia t hat may
include one or more nerves and may alt ernat e sides w it h at t acks; ext raocular
muscle paralysis may occur w it h t he f irst at t ack of headache or, rarely, precede
it ; usually, how ever, t he paralysis appears subsequent t o an est ablished migraine
pat t ern; (c) exclusion of ot her causes, by neuroimaging, surgery, or aut opsy.
Wit h opht halmoplegic migraine, t he t hird nerve paresis reached a maximum as
t he headache began t o resolve and persist ed f or one t o f our w eeks. The t hird
nerve paralysis during t he at t ack is of t en complet e or nearly so, but part ial t hird
nerve paresis, including superior division t hird nerve paresis, may occur [400] .
Most pat ient s have normal neuro-opht halmologic examinat ions bet w een at t acks,
but some pat ient s may demonst rat e part ial t hird nerve paresis or even signs of
aberrant regenerat ion. I n some cases, MRI has revealed enhancement and
enlargement of t he cist ernal port ion of t he oculomot or nerve during t he at t acks
[ 138, 624] .
O cul ar neuromyotoni a (O NM) is a rare disorder charact erized by episodic
(last ing seconds t o minut es) horizont al or vert ical diplopia, occurring eit her
spont aneously or f ollow ing sust ained (10 t o 20 seconds) eccent ric gaze [3, 62,
154, 218, 227, 253, 254, 336, 544, 569, 570, 572, 677, 713, 852] . O NM may
aff ect t he oculomot or, t rochlear, or abducens nerve. Most pat ient s have had
prior radiat ion t herapy t o t he sellar or parasellar region (mont hs t o years bef ore
onset of t he O NM) f or t umors, alt hough in some cases no st ruct ural lesion or
hist ory of radiat ion t herapy is not ed. Rarely O NM may be due t o a compressive
lesion, such as an aneurysm [3, 227] , dolichoect at ic basilar art ery [781] , t hyroid
eye disease [154] , Paget 's disease of bone [100] , or cavernous sinus t hrombosis
secondary t o mucormycosis [330] . Banks et al. describe a unique example of
O NM f rom nonirradiat ed, st roke-relat ed int ramedullary lesions of t he
cont ralat eral midbrain and t halamus [56] . O NM is t hought t o ref lect impaired
muscle relaxat ion due t o inappropriat e discharges f rom oculomot or, t rochlear, or
abducens neurons or axons w it h unst able cellular membranes.
Trochlear Nerve (Cranial Nerve IV)
Anatomy
The t rochlear nucl eus lies caudal t o t he oculomot or nuclear group, dorsal t o t he
MLF, and at t he level of t he inf erior colliculus, just vent rolat eral t o t he cerebral
aqueduct (Figs. 8-7 and 8-8) [112, 281] . The nerve f asci cl es course
post eroinf eriorly around t he aqueduct t o decussat e in t he dorsal midbrain in t he
ant erior medullary velum; t hey t hen emerge f rom t he brainst em near t he dorsal
midline, immediat ely below t he inf erior colliculi. The cist ernal segment t hen runs
ant eriorly over t he lat eral aspect of t he brainst em, successively t raversing t he
quadrigeminal, ambient , crural, and pont omesencephalic cist erns [281] ; t he
cist ernal part of t he nerve is closely relat ed t o t he t ent orium cerebelli (Fig. 8-8).
Af t er t raveling on t he undersurf ace of t he t ent orial edge, it pierces t he dura at a
point slight ly below t he point of ent ry of t he oculomot or nerve int o t he cavernous
si nus along t he lat eral aspect of t he clivus just below t he pet roclinoid ligament .
Wit hin t he lat eral w all of t he cavernous sinus, t he t rochlear nerve lies below t he
oculomot or nerve and above t he opht halmic division of t he t rigeminal nerve, w it h
w hich it shares a connect ive t issue sheat h [480] . The t rochlear nerve ent ers t he
orbit t hrough t he superior orbit al f issure and innervat es t he SO muscle (see Fig.
7-4).
A summary of t he localizat ion of lesions is provided in Table 8-4. Fourth crani al
nerve pal si es may cause t he f ollow ing [821, 820] :
1. I ncomit ant hypert ropia demonst rat ed w it h t he t hree-st ep maneuver. The

hypert ropia increases on head t ilt t ow ard t he paralyzed side (posit ive
Bielschow sky's t est ). Hypot ropia may occur in t he normal eye if t he aff ect ed
eye is f ixat ing; if t he unaff ect ed eye is f ixat ing, hypert ropia occurs in t he
involved eye. This hypert ropia is usually most prominent in t he f ield of gaze
of
t he involved SO muscle (i. e. , dow n and in), especially in cases of acut e or

recent onset . The hypert ropia may also be most prominent in t he f ield of
gaze of t he ipsilat eral overact ing I O muscle in subacut e or chronic cases or
evident in t he ent ire paret ic f ield (spread of comi tance). Duct ion t est ing may
variably reveal underact ion of t he ipsilat eral SO muscle, overact ion of t he
ipsilat eral I O muscle, or overact ion of t he cont ralat eral SO muscle. Pseudo-
overact ion of t he SO in t he uninvolved eye occurs w it h spread of comit ance
and secondary cont ract ure of t he SR muscle in t he involved eye w it h t he
hypert ropia involving t he ent ire low er f ield of gaze. I n a pat ient w it h an SO
muscle paralysis w ho habit ually f ixat es w it h t he paret ic eye and in w hom
overact ion of t he ipsilat eral I O muscle has developed, less t han t he normal
amount
of innervat ion w ill be required w hen t he pat ient looks up and t o t he

cont ralat eral side. Since t he innervat ion f low ing t o t he opposit e SR is
“det ermined” by t he overact ing ipsilat eral I O (Hering's law ), t he opposit e SR
muscle w ill seem paret ic (i nhi bi ti onal pal sy of the contral ateral antagoni st).
I n t hese cases, t he head t ilt t est w ill correct ly det ermine w hich of t he t w o
eyes is paret ic.
FI G URE 8-7 Diagram of t he t rochlear nerve (cranial nerve I V). Cross

sect ion of low er midbrain show s t he nucleus and course and dist ribut ion
t o t he superior oblique muscle of t he opposit e eye. (From Daube JR,
Regan TJ, Sandok BA, et al. Medi cal neurosci ences: an approach to
anatomy, pathol ogy, and physi ol ogy by system and l evel s, 2nd ed.
Bost on, MA: Lit t le, Brow n and Company, 1986. By permission of Mayo
Foundat ion. )
FI G URE 8-8 Diagram illust rat ing normal course of f ourt h cranial nerve (I V
N), CA = caroti d art ery; N = nerve; I I , I I I , V, VI = opti c, oculomot or,
t rochlear, t rigeminal, and abducens nerves, respect ively, V1, V2, and V3
= three divisions of cranial nerve V. (From G ent ry LR, Meht a RC, Appen
RE, et al. MR imaging of primary t rochlear nerve neoplasms. Am J
Neuro-Radi ol ogy 1991; 12: 707–713. Reprint ed w it h permission. )
TABLE 8-4 The Localization of Trochlear Nerve

Lesions
Structure
Clinical Manifestation
Involved
Lesions affecting the trochlear nucleus and/or

fascicles (SO palsy contralateral to lesions)
Nucleus/Fascicles
Isolated trochlear palsy (rare)
alone
Vertical gaze palsy (Dorsal

Pretectal region
midbrain syndrome)
Superior
cerebellar Dysmetria on side of lesion
peduncle
Descending Horner syndrome on side of

sympathetic fibers lesion
Ipsilateral paresis of adduction

Medial longitudinal
with nystagmus of contralateral
fasciculus
abducting eye
Contralateral relative afferent
Brachium of pupillary defect without visual
superior colliculus impairment
Anterior medullary Bilateral trochlear nerve

velum palsies
Lesions affecting the trochlear nerve within the

subarachnoid space (SO palsy usually ipsilateral to
lesion unless mesencephalon compressed)
Trochlear nerve
Isolated trochlear palsy
alone
Superior
cerebellar Ipsilateral dysmetria
peduncle
Cerebral peduncle Contralateral hemiparesis
Lesions affecting the trochlear nerve within the

cavernous sinus and/or superior orbital fissure
Trochlear nerve
Isolated trochlear palsy (rare)
alone
CN III, VI, Ophthalmoplegia; pupil small,

sympathetic large, or spared; ptosis
CN V (Ophthalmic Facial/retro-orbital pain,

division) sensory loss (forehead)
Increased venous Proptosis, chemosis
pressure
Lesions affecting the trochlear nerve within the orbit
Trochlear nerve,
trochlea, SO SO palsy
muscle or tendon
Mechanical
Brown's superior oblique
restriction of SO
tendon sheath syndrome
tendon
Other ocular motor

Ophthalmoplegia, ptosis,
nerves/extraocular
restricted ocular movements
muscles
Visual loss, optic disc

Optic nerve
swelling/atrophy
Proptosis (occasionally
Mass effect enophthalmus); chemosis,
eyelid swelling; and so on.
SO = superior oblique; CN = cranial nerve.
2. Excyclot ropia, w hich is usually evident on f undus exam and double Maddox
rod t est ing (Maddox rods of diff erent colors over each eye) [787] . This
cyclot ropia is sympt omat ic only in acquired (vs. congenit al) cases.
3. Head t ilt , w hich is incorporat ed t o eliminat e t he hypert ropia and rarely t he
cyclot ropia. This head t ilt is present in approximat ely 70% of pat ient s and is
usually aw ay f rom t he involved
side but may be paradoxical (t ow ard t he involved side) in about 3%.

Paradoxical head t ilt presumably result s in a great er separat ion of images,
t hereby allow ing one of t he images t o be ignored.
I t is import ant t o diff erent iat e pat ient s w it h decompensati on of a congeni tal
f ourth nerve pal sy f rom t hose w it h an acquired f ourt h nerve palsy. The f ollow ing
diff erences can be seen in pat ient s w it h congenit al f ourt h nerve palsies:
1. O ld phot os may show head t ilt .

2. Pat ient s are usually not ed t o have cyclot ropia on examinat ion but do not
complain of cyclot ropia (subject ive image t ilt ing) as do some pat ient s w it h
acquired f ourt h nerve palsies.
3. Large vert ical f usional amplit udes (>6 t o 8 prism diopt ers) in primary gaze
are charact erist ic of congenit al cases.
4. Facial asymmet ry (hypoplasia on side of head t urn) suggest s a congenit al
lesion.
Bi l ateral f ourth nerve pal si es result in an inabilit y t o depress eit her eye f ully in
adduct ion. There may be associat ed bilat eral overact ion of t he I O muscles.
Bilat eral f ourt h nerve palsies are suggest ed by t he f ollow ing [463, 821, 820] :
1. A right hypert ropia in lef t gaze and lef t hypert ropia in right gaze
2. A posit ive Bielschow sky t est on t ilt t o eit her shoulder (“double Bielschow sky
t est ”)
3. A large excyclot ropia (>10 degrees)
4. V-pat t ern ET (15 prism diopt ers or more diff erence in ET bet w een upw ard
and dow nw ard gaze); t he “V” pat t ern is caused by a decrease of t he
abduct ing eff ect of t he SO (s) in depression and overact ion of t he SO
muscle(s)
5. Underact ion of bot h SO muscles and/ or overact ion of bot h I O muscles
6. I n general, bilat eral f ourt h nerve palsies t end t o have a smaller hypert ropia
in primary posit ion t han do unilat eral f ourt h nerve palsies
Alt hough t rochlear nerve palsy account s f or most cases of acquired vert ical
st rabismus [480] , t rochlear nerve palsies are less commonly recognized t han
oculomot or or abducens nerve palsies [78, 647] .
A lesion involving t he trochl ear nucl eus or i ts f asci cl es may result in
cont ralat eral paresis of t he SO muscle [167] . Unilat eral or bilat eral SO palsy
may occur w it h nont raumat ic et iologies, including nuclear aplasia, mesencephalic
st roke, t umor, art eriovenous malf ormat ion, and demyelinat ion [160, 406, 421,
429, 428, 465, 480, 679, 808] . Acquired bilat eral SO palsies may occur w it h
lesions aff ect ing t he dorsal midbrain or superior medullary velum [60, 589, 750,
808] . Alt hough an isolat ed t rochlear nerve palsy may be t he sole or f irst sign of
a dorsal mesencephalic t umor, hemorrhage, inf arct ion, or mult iple sclerosis [264,
369, 406, 446, 540, 764, 768] , most mesencephalic lesions causing t rochlear
nerve palsies bet ray t heir presence by causing damage t o neighboring st ruct ures
[ 112] . Nont raumat ic bilat eral f ourt h nerve palsies, of t en associat ed w it h ot her
midbrain signs, may be due t o pinealoma, hydrocephalus, demyelinat ing disease,
neurosurgical complicat ion, subdural hemat oma w it h herniat ion, met ast asis,
vascular malf ormat ion, and midbrain inf arct ion or hemorrhage (all processes
aff ect ing t he dorsal midbrain or ant erior medullary velum) [112, 160, 679] .
Unilat eral lesions involving t he f ourt h nerve nucleus or it s f ascicles, bef ore
decussat ion in t he ant erior medullary velum, and adjacent sympat het ic f ibers
may produce an ipsilat eral Horner syndrome and cont ralat eral SO paresis [167,
307, 559] . A unilat eral mesencephalic lesion aff ect ing t he t rochlear nerve nucleus
(or it s f ibers prior t o decussat ion) and t he MLF may cause an ipsilat eral
int ernuclear opht halmoplegia and a cont ralat eral SO palsy [802] . A lesion
aff ect ing t he brachium of t he SC and t he adjacent t rochlear nucleus or f ascicle
may cause a contral ateral relat ive aff erent pupillary def ect w it hout visual
impairment (see Chapt er 7) and a contral ateral SO paresis [223] . Vent rolat eral
ext ension of t he lesion t o t he superior cerebellar peduncle may produce
ipsilat eral dysmet ria and t runcal at axia. Bilat eral SO paresis associat ed w it h
unilat eral spinot halamic t ract damage has been described w it h a small
spont aneous mesencephalic t egment um hemorrhage [213] .
I n children and adult s, congenit al abnormalit ies and t rauma are t he most common
causes of isolat ed unilat eral or bilat eral t rochlear nerve palsy in w hich an
et iology can be det ermined [410, 413, 647] . Even minor head t rauma may induce
a t rochlear nerve palsy in pat ient s on ant icoagulant s or in pat ient s w it h
preexist ing st ruct ural disorder [371] . I t s long course around t he mesencephalon,
near t he edge of t he t ent orium, makes t his nerve part icularly vulnerable, and a
blow t o t he f orehead may cause a cont recoup cont usion of one or bot h f ourt h
nerves by shoving t he nerve up against t he rigid t ent orium [45] . Severe f ront al
head t rauma may cause bilat eral f ourt h nerve palsies, probably due t o cont usion
of t he ant erior medullary velum.
I n t he absence of ot her signs, it may be essent ially impossible t o make a t opical

diagnosis of an isolat ed t rochlear nerve palsy w it hout neuroradiologic
assist ance. I schemic neuropat hy caused by diabet es or ot her vasculopat hies can
aff ect any segment of t he t rochlear nerve. Vasculopat hic t rochlear nerve palsy
of t en resolves spont aneously w it hin 4 t o 6 mont hs [447, 670] . I n t he
subarachnoi d space, isolat ed f ourt h nerve palsy may occur w it h a superior
cerebellar art ery aneurysm at t he level of t he ambient cist ern [9, 163] , w it h an
int ernal carot id post erior communicat ing art ery aneurysm [708] , or w it h a
primary t rochlear nerve neoplasm (e. g. , schw annoma or neurof ibroma) [232] .
The lat t er should be especially considered in pat ient s w it h neurof ibromat osis
[ 281, 682] . Pit uit ary t umors may rarely present w it h an isolat ed t rochlear nerve
palsy [606] . A f ourt h nerve palsy associat ed w it h homonymous hemianopia and
hemisensory def icit w as described w it h a proximal post erior cerebral art ery
aneurysm [312] . Diff use meningeal processes (e. g. , meningit is) may cause
unilat eral or bilat eral f ourt h nerve palsies [673] . Wit h ot her lesions, precise
localizat ion depends on t he damage done t o neighboring st ruct ures. As t he nerve
courses ant erolat erally around t he midbrain, involvement of t he superior
cerebellar peduncle bef ore t he decussat ion may be manif est by ipsilat eral
cerebellar signs. A cont ralat eral hemiparesis, predominant ly involving t he leg,
w ould locat e t he lesion more ant eriorly w here t he nerve sw ings around t he
cerebral peduncle. Tent orial meningiomas can cause t he syndromes just
described. G uillain-Barré syndrome or Fisher syndrome usually aff ect s ot her
ocular mot or nerves as w ell [755] . Wit hin t he subarachnoid space, t he nerve may
also be injured by neurosurgical procedures, and it is probably here t hat nerve
injury occurs f ollow ing lumbar punct ure or spinal anest hesia [433] . Fourt h nerve
palsy has been described w it h superf icial siderosis of t he cent ral nervous
syst em [331, 709] . Rarely, pseudot umor cerebri may be associat ed w it h a f ourt h
nerve palsy [464, 730] .
Lesions in t he cavernous si nus or superi or orbi tal f i ssure may involve all t he
ocular mot or nerves and t he opht halmic branch of t he t rigeminal nerve, w it h
subsequent ret ro-orbit al pain on t he aff ect ed side [415] . An isolat ed t rochlear
nerve palsy may be produced by an int racavernous int ernal carot id art ery
aneurysm [27] , a dural carot id-cavernous sinus f ist ula [701] , or a cavernous
sinus meningioma [719] . An isolat ed t rochlear nerve palsy may occur w it h herpes
zost er opht halmicus [25, 302, 480, 688, 757 or ot icus [403] , neonat al hypoxia,
encephalit is, and as a complicat ion of coronary angiography and bypass surgery.
Alt hough orbi tal processes may damage t he t rochlear nerve, more of t en direct
damage t o t he SO muscle or t rochlea is responsible f or vert ical diplopia w it h an
orbit al lesion [135] . Trauma, t umor, or ot her inf ilt rat ive processes are t he usual
et iologies. Mot ion of t he SO may be rest rict ed by a t enosynovit is t hat prevent s
t he t endon f rom passing f reely t hrough t he t rochlear pulley. Forced duct ion can
be used t o unmask t his mechanical rest rict ion of depression on adduct ion.
Rarely, myast henia gravis may present w it h isolat ed SO w eakness simulat ing a
t rochlear nerve lesion [669] . Thyroid opht halmopat hy may present w it h w hat
appears t o be a unilat eral SO paresis (likely act ually caused by a rest rict ive
process of t he opposit e I R muscle) [552] . Decompensat ion of a lat ent SO palsy
may occur during pregnancy, result ing in diplopia t hat of t en resolves short ly af t er
delivery [364] .
The et iologies of t rochlear nerve palsies, based on t opographical localizat ion,
are out lined in Table 8-5 [ 465] .
I nvolvement of t he t rochlear nerve should alw ays be sought in t he presence of a
TNP. I n t his inst ance, adduct ion w eakness prevent s t he SO f rom depressing t he
eye. I f t he SO is f unct ional, how ever, it int ort s t he eye w hen t he pat ient is asked
t o look dow n. This eye int orsion is subt le and best not ed by w at ching t he
movement of a horizont ally locat ed conjunct ival vessel.
Myokymi a of the SO muscl e, a uniocular rot at ory microt remor, may cause
episodes of vert ical oscillopsia, shimmering, or t ransient diplopia [117, 661] .
This condit ion is usually benign. I t may f ollow a SO palsy and has a nat ural
hist ory of recurrent spont aneous remissions and relapses. The myokymia may
occur in primary posit ion or be induced by movement s int o or aw ay f rom t he
direct ion of act ion of t he SO muscle. Superior oblique myokymia (SO M) may
rarely be an isolat ed manif est at ion of t ect al disease [185, 548] . SO M has also
been described w it h lead int oxicat ion and adrenoleukodyst rophy [566] .
Neurovascular compression of t he t rochlear nerve at t he root exit zone may be
responsible f or SO M [859] . This monocular disorder has bot h phasic and t onic
component s and is t hought t o be due t o dysf unct ion rest rict ed t o t he SO mot or
unit , perhaps spont aneous discharge of t rochlear mot or neurons t hat have
undergone regenerat ive changes [478, 776] .
TABLE 8-5 Etiologies for a Fourth Nerve Palsy Based

on Clinical Topographical Localization
Midbrain (nuclear/fascicular)
Aplasia of the nucleus
Arteriovenous malformation
Demyelination
Hemorrhage
Ischemia/infarction
Tumor (e.g., glioma)
Trauma (including surgical)
Sarcoidosis
Arachnoid cyst of quadrigeminal cistern
Subarachnoid space
Aneurysm (e.g., superior cerebellar artery)
Hydrocephalus
Infections
Mastoiditis
Meningitis
Sarcoidosis
Superficial siderosis of central nervous system
Postlumbar puncture or spinal anesthesia
Pseudotumor cerebri
Trauma, including surgery
Neoplasm
Carcinomatous meningitis
Cerebellar hemangioblastoma
Ependymoma
Meningioma
Metastasis
Neurolimomma/schwannoma
Pineal tumors
Trochlear nerve sheath tumors
Fisher syndrome
Churg-Strauss syndrome
Cavernous sinus
Neoplasm (e.g., meningioma, pituitary adenoma)
Infectious
Herpes zoster
Mucormycosis
Inflammation
Tolosa-Hunt syndrome
Internal carotid artery aneurysm
Dural carotid-cavernous sinus fistula
Superior ophthalmic vein thrombosis
Foramen ovale electrode placement
Balloon test occlusion of cervical internal carotid
artery
Orbit
Neoplasm
Infection
Infiltration
W aldenstrom's macroglobulinemia
Inflammation
Progressive systemic sclerosis
Trauma
Orbital floor fracture
Other
Migraine
Congenital
Cephalic tetanus

Acqui red verti cal di pl opi a is most of t en due t o oculomot or palsies, t rochlear
palsies, and skew deviat ion (see subsequent t ext ), but it may also be caused by
myast henia gravis, t hyroid orbit opat hy, G uillain-Barré syndrome, orbit al f loor
f ract ure, orbit al pseudot umor or inf ilt rat ion, Brow n's syndrome, Fisher syndrome,
bot ulism, CPEO , vert ical one-and-a-half syndrome (see subsequent t ext ), and
monocular supranuclear gaze palsy (see subsequent t ext ) [115, 407, 460, 727,
804] . An asympt omat ic physiologic hyperdeviat ion on peripheral gaze, most of t en
simulat ing t he phenomenon of overact ion of t he I O s, has been described [720] .
Pat ient s w it h sixt h nerve palsies may also have an associat ed hyperdeviat ion,
usually maximal t o t he side of t he palsy, t hought t o be due t o mechanical f act ors
[ 718, 843] . Small vert ical deviat ions in sixt h nerve palsy are consist ent w it h
normal hyperphorias t hat become manif est in t he presence of ET. I n peripheral
sixt h nerve palsy, st at ic head roll t o eit her side induces hyperdeviat ion in t he eye
on t he side of t he head t ilt . Hyperdeviat ion of t he same eye induced by head t ilt
t o eit her direct ion implicat es a brainst em lesion as t he cause of paret ic
abduct ion. Q uant it at ive st udy of sixt h nerve palsy demonst rat es t hat if a vert ical
deviat ion f alls w it hin t he normal range of hyperphoria, mult iple CN palsy or skew
deviat ion may not be
responsible. Conversely, vert ical deviat ion >5 PD indicat es skew deviat ion or
peripheral nerve palsy in addit ion t o abduct ion palsy. This abducens-associat ed
vert ical deviat ion may account f or t he vert ical diplopia not ed in some pat ient s
w it h pseudot umor cerebri [44] .
Abducens Nerve (Cranial Nerve VI)
Anatomy
The paired abducens nucleus is locat ed in t he dorsal low er port ion of t he pons,
separat ed f rom t he f loor of t he f ourt h vent ricle by t he genu of t he f acial nerve
(f acial colliculus) (Fig. 8-9). The abducens mot oneurons are int ermixed w it h
int ernuclear neurons t hat send t heir axons across t he midline t o t he opposit e
MLF, w here t hey ascend t hrough t he pons and midbrain t o end in t he t hird nerve
nucleus. Theref ore, t he abducens nuclear complex coordinat es t he act ion of bot h
eyes t o produce horizont al gaze. Axons of t he abducens mot oneurons course
ant eriorly in t he pons, t hrough t he medial lemniscus and medial t o t he f acial
nerve f ascicles, t o emerge in t he horizont al sulcus bet w een t he pons and
medulla, lat eral t o t he cort icospinal bundles. The abducens nerve t hen ascends
along t he base of t he pons in t he preponti ne ci stern and ent ers Dorel l o's canal
beneat h G ruber's (pet roclinoid) ligament (see Fig. 7-4). I n t he lat eral w all of t he
t ext it cavernous sinus, it lies bet w een t he carot id art ery medially and t he
opht halmic branch of t he t rigeminal nerve lat erally (Fig. 8-5; also Fig. 7-4). I n
t heir course f rom t he pericarot id plexus t o t he opht halmic branch of t he
t rigeminal nerve, t he pupil's sympat het ic f ibers join t he abducens nerve f or a f ew
millimet ers. Af t er passing t hrough t he superi or orbi tal f issure, t he abducens
nerve innervat es t he lat eral rect us muscle.
FI G URE 8-9 The abducens nerve show n arising f rom t he nucleus in t he pons
t o t ravel t hrough t he cavernous sinus and superior orbit al f issure t o t he
lat eral rect us muscle. (From Daube JR, Regan TJ, Sandok BA, et al. Medi cal
neurosci ences: an approach to anatomy, pathol ogy, and physi ol ogy by
system and l evel s, 2nd ed. Bost on, MA: Lit t le, Brow n and Company, 1986.
By permission of Mayo Foundat ion. )
Table 8-6 summarizes t he localizat ion of lesions. Et iologies of abducens nerve
palsies based on localizat ion is out lined in Table 8-7 [ 465] .
Lesions aff ect ing t he abducens nucl eus cause not only an ipsilat eral lat eral
rect us paresis but also an ipsilat eral gaze palsy t o t he same side because t he
abducens int erneurons are involved. Lesions of t he abducens nucleus occurring
early in lif e can cause Möbius syndrome or Duane's ret ract ion syndrome. I n
addit ion t o horizont al gaze dist urbances, pat ient s w it h Möbi us syndrome have
f acial diplegia and may have ot her CN abnormalit ies. Möbius syndrome is of t en
more t han a CN or nuclear development al disorder. I n a st udy of 37 pat ient s w it h
t his disorder and f acial w eakness, 97% had bilat eral and 3% had unilat eral
ocular abduct ion w eakness [815] . Furt her analysis show ed isolat ed abducens
nerve palsy in 9%, a conjugat ed horizont al gaze paresis in 48%, f eat ures of
Duane ret ract ion syndrome in 34%, and congenit al f ibrosis of t he ext raocular
muscles in 9%. O t her signs included lingual involvement (77%), dysf unct ion of
palat e and pharynx (56%), general mot or disabilit y (88%), poor coordinat ion
(83%),
and respirat ory abnormalit ies (19%). Möbius syndrome may t heref ore be
considered as a disorder of rhombencephalic maldevelopment involving
predominant ly mot or nuclei and axons, as w ell as t raversing long t ract s [815] .
The disorder may be associat ed w it h gaze palsies, Duane's ret ract ion syndrome,
f eeding and respirat ory problems, and poor mot or development [815] .
TABLE 8-6 The Localization of Abducens Nerve

Lesions
Structure
Clinical Presentation
Involved
Lesions affecting abducens nucleus
Gaze palsy
Möbius syndrome (gaze palsy with facial
Abducens diplegia)
nucleus Duane's retraction syndrome (gaze palsy
with globe retraction and narrowing of
palpebral fissure with adduction)
Ipsilateral gaze palsy, facial paresis,

Dorsolateral
dysmetria; occasionally with
pons
contralateral hemiparesis (Foville's)
Lesions of the abducens fascicle
Abducens
Isolated CN VI palsy
fascicle
Anterior Ipsilateral CN VI palsy, ipsilateral CN VII

paramedial palsy, contralateral hemiparesis (Millard-
pons Gubler)
CN VI palsy with or without contralateral

Prepontine
hemiparesis (if corticospinal tract
cistern
involved)
Lesion of abducens nerve
Petrous
apex CN VI palsy, deafness, facial (especially
(Dorello's retro-orbital) pain (Gradenigo)
canal)
Isolated CN VI palsy; CN VI palsy plus

Cavernous
Horner syndrome; also may affect CN III,
sinus
IV, V1
Superior
orbital CN VI palsy with variable affection of CN
fissure III, IV, V1; proptosis
syndrome
CN VI palsy; visual loss; variable

Orbit
proptosis, chemosis, lid swelling
CN = Carnival nerve.
Duane's retracti on syndrome is charact erized by a narrow ing of t he palpebral

f issure and occasionally globe ret ract ion on adduct ion [155] . Three f orms have
been described [198] . I n t ype 1, abduct ion is limit ed, but adduct ion is normal.
Some pat ient s have impaired adduct ion but normal abduct ion (t ype 2), w hereas
ot hers have impairment of bot h (t ype 3). These pat ient s seldom complain of
diplopia, alt hough t his sympt om may develop lat er in lif e. Pat ient s are not usually
esot ropic in primary gaze, do not develop amblyopia, and do not not e diplopia if
t hey are able t o look in t he f ield of t he paret ic muscle (f acult at ive amblyopia). I n
all t ypes, t here may be a vert ical deviat ion of t he adduct ing eye t hat t akes t he
f orm of “upshoot s” and “dow nshoot s. ” Unilat eral t ype 1 syndrome may rarely be
associat ed w it h rest rict ion of upgaze in t he aff ect ed eye [508] . The abducens
nerve on t he aff ect ed side is absent in t ype 1 Duane's ret ract ion syndrome
pat ient s and some t ype 3 pat ient s, but is present in t ype 2 Duane's pat ient s as
w ell as in some t ype 3 pat ient s [424] . I n t erms of t he presence or absence of
t he abducens nerve, t ype 1 and t ype 2 Duane's ret ract ion syndrome w ere
homogenous, and t ype 3 Duane's ret iact ion syndrome w as het erogenous.
Alt hough Duane's ret ract ion syndrome is predominant ly congenit al, and is t hought
t o be due t o anomalous innervat ion of t he lat eral rect us muscle by t he inf erior
division of t he oculomot or nerve [198] , acquired Duane's syndrome has been
described in pat ient s w it h pont ine glioma, w it h rheumat oid art hrit is, f ollow ing
t rigeminal rhizot omy, and af t er removal of an orbit al cavernous hemangioma by
lat eral orbit ot omy [198] .
Ponti ne tegmental lesions are discussed in great er det ail in t he sect ion on
cent ral dist urbances of eye movement s. Acut e lesions of t he low
dorsol ateral pons cause an ipsilat eral gaze palsy, f acial paresis, and t erminal
dysmet ria. A more ext ensive unilat eral lesion causes cont ralat eral hemiparesis
(Fovi l l e's syndrome), usually due t o inf arct ion in t he t errit ory of t he ant erior
inf erior cerebellar art ery. More anteri or paramedi al lesions spare t he abducens
nucleus but aff ect t he f ascicles, result ing in ipsilat eral abducens and f acial
w eakness w it h cont ralat eral hemiparesis (Mi l l ard-G ubl er syndrome). Such
lesions are of t en ischemic, but t hey also include neoplasms, granulomas,
mult iple sclerosis plaques, or Wernicke's encephalopat hy. Rarely, inf arct ion,
t umor, or hemorrhage aff ect ing t he abducens nerve f ascicle may cause an
isolat ed sixt h nerve palsy [123, 210, 257, 382, 427, 761] , and chroni c i sol ated
sixt h nerve palsies have been described w it h pont ine glioma and ext ra-axial
t umors [178, 267] . An acut e sixt h nerve palsy may be a prominent or present ing
sympt om of mult iple sclerosis [744, 761, 766 and an isolat ed f ascicular
abducens palsy has been described w it h Lyme disease [514] .
TABLE 8-7 Etiology of a Sixth Nerve Palsy by

Topographical Localization
Nuclear (Horizontal gaze)

Congenital (e.g., Möbius syndrome)
Demyelinating
Infarction or ischemia
Neoplasm (pontine and cerebellar)
Histiocytosis X
Trauma
W ernicke-Korsakoff syndrome
Fascicular
Demyelination
Infarction
Neoplasm
Anti-Hu paraneoplastic brainstem encephalitis
Trauma
Hematoma
Migraine
Subarachnoid
Aneurysm or vascular abnormality
Persistent primitive trigeminal artery
Posterior inferior cerebellar aneurysm
Vertebral artery
Dolichoectasia of the basilar artery or vertebral
artery
Carcinomatous or leukemic meningitis
Arnold-Chiari malformation or basilar impression
Following procedures
Cervical traction
Lumbar puncture
Myelography
Post vaccination
Radiculography
Shunting for hydrocephalus
Spinal or epidural anesthesia
Intrathecal glucocorticoid injection
Inflammatory
Retropharyngeal space inflammation
Necrotizing vasculitis
Sarcoidosis
Fisher syndrome
Infectious
Lyme disease
Syphilis
Tuberculosis
Cryptococcal meningitis
Cysicercosis
Human immunodeficiency–Cytomegalovirus
encephalitis
W est Nile meningoencephalitis
Pseudomonas skull-based osteomyelitis
Neoplasm
Abducens nerve tumor
Cerebellopontine angle tumor
Clivus tumor (e.g., chordoma, chondrosarcoma,
plasmacytoma)
Leukemia
Plasmacytoma
Metastatic
Skull base tumor
Nasopharyngeal carcinoma
Trigeminal nerve tumor
Capillary hemangioma of Meckel's cave
Nonlocalizing sign of increased intracranial pressure
Pseudotumor cerebri
Meningitis of any type
Intracranial tumor
Venous sinus thrombosis
Syndrome of headache, neurologic deficits, and
cerebrospinal fluid lymphocytosis
Spontaneous cerebrospinal fluid leak with
intracranial hypotension
Trauma (excluding surgical)
Epidural hematoma of clivus (posttraumatic)
Petrous apex
Neoplasm (e.g., nasopharyngeal carcinoma)
Infection
Complicated otitis media
Mastoiditis (Gradenigo's syndrome)
Thrombosis of inferior petrosal or transverse/sigmoid
sinus
Trauma
Basilar skull fracture
Inflammatory
Cavernous sinus
Cavernous sinus thrombosis
Cavernous sinus fistula
Cavernous carotid artery dolichoectasia
Superior ophthalmic vein thrombosis
Neoplasm
Nasopharyngeal carcinoma
Pituitary adenoma
Plasmacytoma
Lymphoma
Hodgkin's disease
Hemangioma
Hemangioendothelioma
Meningioma
Sixth nerve tumors
Sphenoid sinus tumors
Skull base tumors
Squamous cell cancer of pterygopalatine fossa
Subarachnoid diverticulum
Sphenoid sinus mucocele
Ischemia
Inflammatory or infectious
Herpes zoster
Actinomycoses
Actinobacillus actinomycetemcomitans
Tolosa-Hunt syndrome
Internal carotid artery diseases
Aneurysm
Dissection
Dolichoectasia
Balloon test occlusion
Cisplatin infusion
Postradiofrequency rhizotomy for trigeminal
neuralgia
Orbital lesions
Neoplastic
Inflammation
Infectious
Traumatic
Localization uncertain
Infectious mononucleosis
Mycoplasma pneumoniae infection
Lyme disease
Campylobacter jejuni enteritis
Creutzfeldt-Jacob disease
Progressive multifocal leukoencephalopathy in
acquired immunodeficiency syndrome
Lymphoma
Bing-Neel syndrome with W aldenstrom
macroglobulinemia
Bone marrow transplantation treatment with
cyclosporin and ganciclovir
3, 4-Methyl-enedioxymetamphetamine (“ecstasy”)
abuse
Guillain-Barré syndrome
Fisher syndrome
Associated with anti-GQ1b IgG antibody
Chronic inflammatory demyelinating
polyradiculoneuropathy
Pregnancy
Trauma
Dental anesthesia
Migraine
Idiopathic

Lesions t hat aff ect t he abducens nerve in t he preponti ne ci stern may compress
t he ipsilat eral cort icospinal bundles and lead t o cont ralat eral hemiparesis. More
of t en, st ret ching or compression of t he t rigeminal root result s in associat ed
ipsilat eral f acial pain. A f requent cause of isolat ed abducens involvement at t his
level is increased int racranial pressure [445] . O pht halmic manif est at ions,
including decreased vision, papilledema, and sixt h nerve palsy, may occur in t he
syndrome of headache, neurologic def icit s, and cerebrospinal f luid lymphocyt osis
(HaNDL) [543] . Spont aneous int racranial hypot ension f rom a dural cerebrospinal
f luid leak may also cause abducens palsy [22, 354, 482, 537, 580, 691 as may a
lumbar punct ure [767] . Cerebellopont ine angle t umors may involve t he abducens
nerve. Compressive lesions in t he prepont ine cist ern include dolichoect at ic
basilar art eries, aneurysms, meningiomas of t he clivus, chordomas,
chondrosarcomas, schw annomas, and nasopharyngeal carcinomas [246, 289,
325, 803, 818, 819] . I n t he prepont ine cist ern, t he nerve is also exposed t o
t rauma, meningit is, meningeal carcinomat osis, and syndrome G uillain-Barré
syndrome. A sixt h nerve palsy may be t he init ial manif est at ion of sarcoidosis
[ 672] or met ast at ic prost at e cancer [579] . Transient and occasionally recurrent
sixt h nerve palsies may
be t he f irst present at ion of acut e leukemia [34, 839] . I solat ed bilat eral abducens
nerve palsies have occurred w it h t he rupt ure of a vert ebral art ery aneurysm
[ 543A] , and bilat eral palsies have been described w it h West Nile
meningoencephalit is [665] .
Combined abducens nerve and hypoglossal nerve palsies are rare. This is of t en
an ominous combinat ion as it may be seen w it h nasopharyngeal carcinoma
(G odtf redsen syndrome) and w it h ot her clival lesions, especially t umors (75% of
w hich are malignant ) [416] . Alt hough t he combinat ion of abducens nerve palsy
w it h hypoglossal nerve palsy usually localizes t he pat hologic process t o t he
clivus, low er brainst em lesions and subarachnoid processes (e. g. , cyst icercal
meningit is) may also cause t his unusual dual CN impairment [416] .
O n t he basis of neurologic f indings alone, it may be diff icult at t imes t o
det ermine w het her t he nerve has been injured w it hin t he subarachnoid space or
in it s petrous porti on, in t he Dorello's canal. Concomit ant involvement of t he
t rigeminal nerve is more likely if t he lesion is in t he pet rous port ion. O t her
clinical f indings may point t o disease in t he pet rous bone, such as an ot ic
discharge f rom chronic ot it is media or mast oidit is, or deaf ness. An inf ect ious or
neoplast ic process t hat spreads t o t he t ip of t he pet rous bone may result in
G radeni go's syndrome, w hich includes abducens nerve paresis, ipsilat eral f acial
(usually ret ro-orbit al) pain, and deaf ness [181] . Trauma, inf erior pet rosal sinus
t hrombosis, vascular malf ormat ions, aneurysms, and t umors may also injure t he
nerve at t his level.
Ret ro-orbit al pain, involvement of ot her ocular mot or nerves and, occasionally,
an ipsilat eral Horner syndrome point t o t he cavernous si nus as t he sit e of t he
lesion. The sympat het ic f ibers t o t he eye join t he abducens nerve f or a short
dist ance w it hin t he cavernous sinus, and t heref ore a unilat eral abducens nerve
lesion associat ed w it h an ipsilat eral Horner syndrome (Parki nson's syndrome) is
of localizing value [1, 715, 742] . Herpes zost er opht halmicus may cause
abducens palsy w it h a Horner syndrome [721] . Similar f indings (w it hout a Horner
syndrome) may be encount ered w it h more ant erior lesions in t he superi or orbi tal
f i ssure. How ever, t umors in t his locat ion may bet ray t heir presence by propt osis.
Pit uit ary adenomas, nasopharyngeal carcinomas, craniopharyngiomas, and
met ast ases most commonly aff ect t he abducens nerve at t he cavernous sinus
and superior orbit al f issure. Sphenoid sinus carcinoma of t en causes a
sphenocavernous syndrome, but may also present w it h an isolat ed sixt h nerve
palsy [326] . Carot id-cavernous sinus dural art eriovenous f ist ulae may present
w it h unilat eral or bilat eral sixt h nerve palsies [468, 796] . Tolosa-Hunt syndrome,
w hich is caused by inf lammat ory processes of various et iologies involving t he
cavernous sinus, present s w it h ocular mot or w eakness and ret ro-orbit al pain.
Facial sensat ion and visual acuit y may be diminished. Tolosa-Hunt syndrome or
painf ul opht halmoplegia is a diagnosis of exclusion [728] . Sudden onset of
headache and dysf unct ion of mult iple ocular mot or nerves on eit her one or bot h
sides, w it h or w it hout ret ro-orbit al pain or visual impairment , suggest s t he
possibilit y of pit uit ary apoplexy [518] . I n t he orbi t, t rauma, t umors, and
inf lammat ory processes can cause abducens w eakness. An orbit al locat ion of
pat hology is suggest ed by associat ed f indings including propt osis, chemosis, and
opt ic nerve involvement .
The abducens nerve may be involved anyw here along it s course by an i schemi c
neuropathy relat ed t o diabet es, collagen-vascular disease, giant cell art erit is,
and parainf ect ious or post inf ect ious art erit ides. Alt hough isolat ed abducens
nerve palsies in pat ient s w it h diabet es are usually at t ribut ed t o ext ra-axial
lesions, isolat ed abducens nerve palsy secondary t o pont ine inf arct ion or
hemorrhage has been described in pat ient s w it h diabet es [256, 257] .
Vasculopat hic sixt h nerve palsies usually recover over a period of 3 t o 6 mont hs.
I t should be not ed t hat early progression of paresis over 1 w eek in vasculopat hic
abducens nerve palsies is not uncommon. I n one st udy, only 2 of 35 pat ient s w it h
ischemic sixt h nerve palsies had init ial complet e abduct ion def icit s [366] . O f 33
pat ient s w it h init ial incomplet e def icit s, 18 (54%) show ed progression over a 1-
w eek period. Elderly pat ient s w ho present w it h an isolat ed sixt h nerve palsy and
headache, scalp t enderness, jaw claudicat ion, or visual loss should undergo an
appropriat e evaluat ion f or giant cell art erit is [553, 644, 687, 686] .
Sanders et al. evaluat ed t he long-t erm prognosis of pat ient s w it h vasculopat hic
sixt h nerve palsy [680] . Fif t y-nine pat ient s w ere ident if ied w it h a mean age of
65. 3 years ± 11. 6 (range 34–90 years). Fif t y-one pat ient s (86%) experienced
complet e resolut ion of t heir f irst episode of vasculopat hic palsy and eight
pat ient s (14%) had incomplet e resolut ion. A subsequent episode of ocular mot or
mononeuropat hy occurred in 18 of 59 (31%) pat ient s. The number of recurrences
ranged f rom one (in 14 pat ient s) t o f our (in one pat ient ). There w as no
associat ion bet w een any risk f act or and recurrence of ocular mot or nerve palsy.
Similarly, incomplet e resolut ion of t he vasculopat hic sixt h nerve palsy w as not
associat ed w it h any risk
f act or. The aut hors concluded t hat pat ient s w it h a vasculopat hic sixt h nerve
palsy usually have complet e resolut ion of t heir opht halmoplegia, but nearly one
t hird of pat ient s in t heir st udy lat er experienced at least one episode of recurrent
vasculopat hic ocular mot or nerve palsy lat er [690] .
Aneurysm is a rare cause of acquired sixt h nerve palsy (vs. oculomot or nerve
palsy). Recurrent , unilat eral, isolat ed, idiopat hic lat eral rect us palsy may occur
in children [7] or adult s [322, 811] . An isolat ed abducens nerve palsy may occur
w it h pregnancy, especially during t he t hird t rimest er [259] . Combined
oculomot or-abducens synkinesis has been described af t er head t rauma [599] .
Pat el et al. st udied 137 new cases of sixt h nerve palsy over t he 15-year period
[ 602] . The age- and gender-adjust ed annual incidence of sixt h nerve palsy w as
11. 3/ 100, 000. Causes and associat ions w ere: undet ermined (26%), hypert ension
alone (19%), coexist ent hypert ension and diabet es (12%), t rauma (12%),
mult iple sclerosis (7%), neoplasm (5%), diabet es alone (4%), cerebrovascular
accident (4%), post neurosurgery (3%), aneurysm (2%), and ot her (8%).
A pseudo-pal sy of the si xth nerve may result f rom excessive convergence. The
most common variet y is spasm of the near ref l ex (see subsequent t ext ). Acut e
ET has been described w it h cont ralat eral t halamic inf arct ion in t he t errit ory of
t he penet rat ing branches of t he mesencephalic art ery (acute thal ami c ET) [ 291] .
Acut e t halamic hemorrhage may cause bilat eral asymmet ric ET w it h t he
cont ralat eral eye more aff ect ed t han t he ipsilat eral eye [344] .
Alt hough a sixt h nerve palsy is probably t he most common cause of an acquired
abduct ion def icit or ET (or bot h), ot her et iologies include t hyroid
opht halmopat hy, myast henia gravis, O NM, orbit al pseudot umor, orbit al t rauma
w it h MR ent rapment , convergence spasm, t halamic ET, Duane's syndrome,
Möbius syndrome, Wernicke-Korsakoff syndrome, divergence paralysis, spasm
of t he near ref lex, midbrain pseudo-sixt h, and cyclic oculomot or palsy [116, 231] .
I mmediat e neuroimaging in pat ient s 50 years of age or older w it h acut e isolat ed
t hird, f ourt h, and sixt h nerve palsies is cont roversial. Chou et al. prospect ively
evaluat ed 66 pat ient s, aged 50 years and older (median 67 years, range 50–85),
w it h acut e isolat ed ocular mot or mononeuropat hies [151] . They f ound t hat clinical
f eat ures, including t ime t o maximal diplopic sympt oms, w ere not predict ive of
et iology (median 2 days t o maximal diplopic sympt oms f or bot h peripheral
microvascular and ot her et iologies). The presence of any common vascular risk
f act or, including diabet es mellit us, hypert ension, hypercholest erolemia, or
coronary art ery disease, w as signif icant ly associat ed w it h peripheral
microvascular et iology in t his cohort . Despit e t he high prevalence of peripheral
microvascular ischemia as an et iology in t his age group, ot her causes w ere
ident if ied by MRI or comput ed t omography (CT) scanning in 14% of pat ient s.
Diagnoses included brainst em and skull base neoplasms, brainst em inf arct s,
aneurysms, demyelinat ing disease, and pit uit ary apoplexy. Neuroimaging
procedures may t heref ore have a role in t he init ial evaluat ion of pat ient s 50
years of age or older w it h acut e ocular mot or mononeuropat hies [151] .
M ultiple Ocular M otor Nerve Palsies
Acut e bilat eral opht halmoplegia may result f rom mult iple causes. I n pat ient s w it h
acut e bilat eral opht halmoplegia, t he lesion t hat is responsible may be localized
t o t he brainst em, t o t he CNs, t o t he region of t he cavernous sinus, and t o t he
myoneural junct ion [197, 405, 480] . Acut e bilat eral opht halmoplegia may be
caused by myast henia gravis, pit uit ary apoplexy, demyelinat ing disease, Fisher
syndrome, brainst em ischemia or hemorrhage, bot ulism, dipht heria, Whipple's
disease, and Wernicke's encephalopat hy [197, 804] .
Because all t hree ocular mot or nerves are supplied by t he inf erolat eral t runk, an
int racavernous branch of t he int ernal carot id [459] , a cavernous sinus vascular
lesion (e. g. , secondary t o diabet es mellit us or t raumat ic int ernal carot id art ery
dissect ion) may cause a complet e unilat eral opht halmoplegia, occasionally w it h
pupillary sparing [503, 805] . Spont aneous dissect ion of t he cervical int ernal
carot id art ery may cause t ransient or persist ant t hird, f ourt h, or sixt h CN palsy
[ 689] .
The t riad of opht halmoplegia, at axia, and aref lexia make up Fi scher syndrome
(due t o a demyelinat ing neuropat hy induced by ant ibodies t hat is t hought t o be a
clinical variant of syndrome G uillain-Barré syndrome) [658, 804] . The init ial
sympt om is usually diplopia; limb and gait at axia appear 3 or 4 days lat er, or at
t imes concurrent ly w it h diplopia. Early ocular f indings include unilat eral or
asymmet ric bilat eral abducens paralysis, but t here are report s of upw ard-gaze
paralysis, pupil-sparing oculomot or nerve palsy, pseudo-int ernuclear
opht halmoplegia, rebound nyst agmus, or divergence paresis [418, 658] . These
usually progress t o bilat eral opht halmoplegia w it hin 2 or 3 days. Pt osis occurs in
most pat ient s, but associat ed pupillary paralysis is unusual. I solat ed pupillary
paralysis w it hout ot her signs of t hird nerve involvement
rarely occurs [837] . Pat ient s w it h Fischer syndrome, part icularly t hose w it h
opht halmoplegia, of t en have ant ibodies direct ed against G Q 1b I gG . Also,
relapsing opht halmoplegia w it h a chronic inf lammat ory demyelinat ing
polyradiculoneuropat h (CI DP) may precede ot her f indings by several w eeks
[ 208] .
The Pupil
Sympathetic and Parasympathetic Innervation
The iris cont ains t w o groups of smoot h muscle w it h reciprocal act ion: t he
sphinct er and t he dilat or. Pupillary size (normal = 2–6 mm, average 3 mm in
ambient light ; smaller in older persons) depends on t he balance bet w een
sympat het ic and parasympat het ic t one. Sympat het ic innervat ion, w hich dilat es
t he pupil, proceeds ipsilat erally f rom t he post erolat eral hypot halamus t hrough
t he lat eral t egment um of t he brainst em, t he int ermediolat eral gray mat t er of t he
cord at t he C8-T2 segment s (ciliospinal cent er of Budge-Waller), t he sympat het ic
chain t o t he superior cervical ganglion, t he carot id plexus, and t he opht halmic
branch of t he t rigeminal nerve, reaching t he pupil t hrough t he long ciliary nerves
(Fig. 8-10; see also Fig. 7-4). From t he Edinger-West phal subnucleus in t he
rost ral port ion of t he t hird nerve nuclear complex, t he parasympatheti c t one
reaches t he const rict or of t he pupil t hrough t he t hird nerve, synapsing f irst in t he
ciliary ganglion, w hich is locat ed behind t he globe in t he orbit on t he t emporal
side of t he opht halmic art ery bet w een t he opt ic nerve and t he lat eral rect us
muscle in close associat ion w it h t he inf erior division of t he oculomot or nerve
(Fig. 8-11; see also Fig. 7-4). The pupillomot or f ibers probably course in t he
periphery of t he oculomot or nerve, immediat ely int ernal t o t he epineurium, and
are sit uat ed superf icially and dorsally in t he subarachnoid segment of t he
oculomot or nerve [561] .
FI G URE 8-10 Sympat het ic innervat ion of t he pupil. The f irst -order neurons
are locat ed in t he post erolat eral hypot halamus. The second-order neurons
are locat ed in t he int ermediolat eral cell column of t he low cervical and upper
t horacic cord. The t hird-order neurons are locat ed in t he superior cervical
ganglion.
Caref ul examinat ion of pupillary react ion t o light and near, and at t ent ion t o
dist inct ive associat ed signs and sympt oms allow s diff erent iat ion of t he
abnormalit ies in pupil size and response t o st imuli. O ld phot ographs may be
helpf ul in def ining t he durat ion of ani socori a (asymmet ry of pupillary size).
G enerally, t he hist ory and examinat ion w ill dist inguish t he major ent it ies causing
an abnormal large pupil (e. g. , TNP, t onic pupil, iris damage, pharmacologic
dilat ion, or sympat het ic irrit at ion) or small pupil (e. g. , Horner
syndrome, simple anisocoria, pharmacologic miosis). Pharmacologic t est ing
f urt her conf irms t he diagnosis and allow s t opographical localizat ion in many
cases.
FI G URE 8-11 Parasympat het ic innervat ion of t he pupil and pat hw ays f or t he
light ref lex.
Pupillary Inequality (Anisocoria)

Except f or midbrain lesions and some unusual cases of bilat eral miosis due t o
sympat het ic damage, st ruct ural lesions impinging on t he pupillomot or pat hw ays
are of t en unilat eral and result in pupillary inequalit y (anisocoria). I f a large pupil
(mydriasis) is poorly react ive t o light and t he visual aff erent syst em is normal,
t hen a def ect in t he eff erent parasympat het ic innervat ion t o t his pupil is likely.
Because t his pat hw ay courses f or t he most part w it h t he t hird nerve, lesions
aff ect ing it are of t en accompanied by a lesser or great er degree of w eakness of
t he ext raocular muscles innervat ed by t he oculomot or nerve and by an impaired
light ref lex (Fig. 8-11).
I f t he light react ion is diff icult t o compare t o t he f ellow eye, t hen a measurement
of t he anisocoria in light and dark may help t o det ermine t he pupillary
abnormalit y. I f t he anisocoria is great er in dim light (st imulat es dilat ion of t he
normal pupil), t hen t he def ect is in t he sympat het ic innervat ion t o t he pupil. I f t he
anisocoria is less in dim light , t hen t he lesion is in t he parasympat het ic
innervat ion t o t he pupil [772] . Pt osis can accompany lesions of eit her pat hw ay; it
t ends t o be rat her severe w it h t hird nerve lesions but is mild and cert ainly
incomplet e w it h lesions of t he sympat het ic pat hw ay, w hich result s in lack of t one
of t he ller's muscle Müller's muscle. Classically, oculosympat het ic paralysis
result s in a Horner syndrome.
Pupillary asymmet ry is of t en t he point of depart ure f or diagnosis of lesions in t he
pupillomot or pat hw ays [465, 772] . If ani socori a i s present and the pupi l l ary l i ght
reacti on i s normal i n both eyes, t hen physiologic (simple) anisocoria [454] ,
Horner syndrome, or sympat het ic irrit at ion should be considered. Several st eps
are t aken t o diagnose t he cause of pupillary asymmet ry.
Simple Anisocoria
I f bot h pupils react normally t o light , t he pat ient may have si mpl e ani socori a
[ 770] .
Bet w een 15% and 30% of t he normal populat ion has a diff erence in pupillary size
of 0. 4 mm or great er [770] . These pat ient s have no associat ed pt osis or dilat ion
lag and no evidence of iris injury or t opical drugs. Topical cocaine w ill dilat e bot h
pupils equally (see pharmacologic t est ing of Horner syndrome in t he subsequent
t ext ).
Sympathetic Dysfunction (Horner Syndrome)

I f t here is anisocoria and bot h pupils respond normally t o light , it is likely t hat
t he smaller pupil is t he abnormal one and t hat t he anisocoria w ill become more
pronounced w hen t he light s in t he examining room are t urned off . While t he light s
are being t urned off , one should look f or a “dilat at ion lag” of t he smaller pupil. I f
present , t here may be more pupillary asymmet ry 5 seconds af t er t he light s are
t urned off t han 15 seconds af t erw ard. A dilat at ion lag implies poor sympat het ic
t one and is t heref ore indicat ive of a Horner syndrome. Horner syndrome
comprises t he t riad of miosis, pt osis (due t o paresis of t he Müller's muscle), and
anhidrosis of t he f orehead [770] . How ever, anhidrosis is inconst ant af t er
post ganglionic lesions. Theoret ically, because t he sympat het ic f ibers t hat
innervat e t he f orehead f ollow t he ext ernal carot id art ery, lesions dist al t o t he
carot id bif urcat ion w ould be unaccompanied by anhidrosis of t he f orehead (Fig.
8-10). How ever, t his is an unreliable sign. Miosis may not be percept ible if t he
pat ient w it h a Horner syndrome is in a st at e of high sympat hot onic act ivit y, such
as marked f ear or anxiet y. I n t hese cases, high levels of circulat ing
norepinephrine dilat e t he pupil.
O t her signs of a Horner syndrome may include low er lid elevat ion (“upside dow n
pt osis” or “reverse pt osis sign”) due t o paresis of t he smoot h muscle at t ached t o
t he inf erior t arsal plat e, apparent enopht halmos, increased accommodat ion, and
ocular hypot ony. Pallor of t he iris, result ing in diff erent colors of t he t w o irides
(het erochromia iridis), may accompany oculosympat het ic paralysis t hat w as
sust ained early in lif e (bef ore age 2) (congenit al Horner syndrome). Progressive
het erochromia may rarely occur w it h an acquired Horner syndrome in adult s and
has been described f ollow ing sympat hect omy, ot her cervical operat ions, and
int ernal carot id cut dow n [203] . The clinical f indings in Horner syndrome are
summarized in Table 8-8.
The diagnosis of Horner syndrome can be conf irmed by inst illing one drop of a
10% cocaine solut ion in bot h t he eyes [396] . Anot her drop is inst illed 1 minut e
lat er, and t he result is read in 45 minut es w it h t he pat ient in t he dark. The
normal pupil dilat es af t er cocaine inst illat ion, w hich blocks t he presynapt ic
reupt ake of norepinephrine at t he neuromuscular junct ion in t he dilat or muscle,
but in Horner syndrome t he pupil f ails t o dilat e. Ant ihypert ensive medicat ions
prevent pupillary dilat at ion by cocaine. A solut ion of 1% hydroxyamphet amine
hydrobromide (w hich releases norepinephrine int o t he synapt ic clef t ) inst illed at
least 48 hours af t er t he cocaine t est , dilat es a pupil in Horner syndrome only if
t he lesion is preganglionic. No pharmacologic t est available w ill diff erent iat e a
f irst -order f rom a second-order neuron Horner syndrome. Theref ore, a
preganglionic Horner syndrome (w it h int act post ganglionic t hird-order neuron)
w ill dilat e af t er administ rat ion of t opical hydroxyamphet amine 1% (Paredrine)
w hile a post ganglionic Horner syndrome pupil w ill not dilat e (no norepinephrine
st ores). I t should be not ed t hat a f alse negat ive Paradrine t est may occur w it h
post ganglionic Horner syndrome during t he f irst w eek af t er injury [209] .
TABLE 8-8 Clinical Findings in Horner Syndrome
Anisocoria due to ipsilateral miosis

Dilation lag (slow dilation of the pupil after the lights
are dimmed)
Ipsilateral mild (usually <2 mm) ptosis (due to
denervation of the Müller's muscle of the upper eyelid)
“Upside down ptosis” (from sympathetic denervation to
the lower eyelid retractors)
Apparent enophthalmos
Increased accommodative amplitude or accommodative
paresis (e.g., patients holds the near card closer to
read)
Transient (acute phase) ocular hypotony and
conjunctival hyperemia
Variable ipsilateral facial anhidrosis
Ipsilateral straight hair in some congenital cases
Heterochromia of the iris (usually congenital but rarely
acquired) 207]
Neurotrophic corneal endothelial failure (pain and
stromal edema) (rare) [866]
Ipsilateral nasal obstruction (rare) [755]

A Horner syndrome may result f rom a lesion anyw here along a t hree-neuron
pat hw ay [206] t hat arises as a f irst -order (cent ral) neuron f rom t he
post erolat eral hypot halamus, descends in t he brainst em and lat eral column of
t he spinal cord t o exit at t he cervical (C8) and t horacic (T1-T2) levels (ciliospinal
cent er of Budge) of t he spinal cord as a second-order neuron. This second-order
(int ermediat e) preganglionic neuron exit s t he vent ral root and arches over t he
apex of t he lung t o ascend in t he cervical sympat het ic chain. The second-order
neurons synapse in t he superior
cervical ganglion and exit as a t hird-order neuron. The neural f ibers responsible
f or sw eat ing of t he f ace t ravel w it h t he ext ernal carot id art ery. The t hird-order
post -ganglionic neuron t ravels w it h t he carot id art ery int o t he cavernous sinus,
on t o t he abducens nerve f or a short course, and t hen t ravels w it h t he
opht halmic division of t he t rigeminal nerve t o join t he nasociliary branch of t he
t rigeminal nerve, passes t hrough t he ciliary ganglion, and reaches t he eye as
long and short ciliary nerves.
Pat ient s w it h a central or f i rst-order Horner syndrome can usually be ident if ied
by t he presence of associat ed hypot halamic, brainst em, or spinal cord signs or
sympt oms. A cent ral Horner syndrome may be seen w it h hypot halamic inf arct ion,
hemorrhage, or t umor [33, 560, 738] , but it occurs more commonly f ollow ing
brainst em vascular lesions. Horner syndrome may occur w it h midbrain inf arct ion
[ 72] or ant erior spinal art ery t hrombosis [724] and is part of t he lat eral
medullary syndrome of Wallenberg [111, 430] . The alt ernat e clinical pat t ern of a
cent ral Horner syndrome w it h cont ralat eral at axic hemiparesis is a st roke
syndrome of t he diencephalic–mesencephalic junct ion, result ing f rom t he
involvement of t he common art erial supply t o t he paramedian/ ant erior t halamus,
t he post erior hypot halamus and t he rost ral paramedian midbrain [666] . A Horner
syndrome involving t he f irst -order neurons has been report ed in midbrain lesions
w it h a cont ralat eral t rochlear nerve palsy [167, 307, 559 and w it h bilat eral
abducens palsy due t o pont ine inf arct ion [422] . G iant cell art erit is has been
associat ed w it h a unilat eral int ernuclear opht halmoplegia and an ipsilat eral
Horner syndrome [31] . Lyme disease may result in a reversible preganglionic or
cent ral Horner syndrome [285] .
The pregangl i oni c (i ntermedi ate or second-order) Horner syndrome pat ient may
have neck or arm pain, anhidrosis involving t he f ace and neck, brachial
plexopat hy, vocal cord paralysis, or phrenic nerve palsy. Neoplasm locat ed in t he
neck, head, brachial plexus, or lung (e. g. , glomus t umors, breast cancer,
sarcomas, lung cancer, lymphoret icular neoplasms, neurof ibroma, or t hyroid
adenoma [248a) may cause a second-order Horner syndrome as may mediast inal
or neck lymphadenopat hy. I n pat ient s w it h cancer and a brachial plexopat hy, a
Horner syndrome appears more of t en w it h met ast at ic disease t han w it h radiat ion
injury [443] . Pancoast t umor of t en involves t he sympat het ic chain [32] . Mass
lesions in t he neck may produce a preganglionic Horner syndrome associat ed
w it h vocal cord paralysis and phrenic nerve palsy (Rowl and-Payne syndrome)
[ 360] . Cervicot horacic abnormalit ies causing a Horner syndrome include a
cervical rib, pachymeningit is, hypert rophic spinal art hrit is, f oraminal ost eophyt e,
rupt ured int ervert ebral disc, t horacic aneurysm, herpes zost er in T3-T4
dist ribut ion, and cont inuous t horacic epidural analgesia [496, 621] . Neck,
brachial plexus or lung t rauma or surgery, including birt h t rauma (Klumpke's
paralysis), upper cervical sympat hect omy, ant erior C3-C6 f usion, and radical
t hyroid surgery may also cause a Horner syndrome [597, 724] . O t her causes of
second-order Horner syndrome include int ernal jugular vein t hrombosus in
polycyt hemia vera [286] , t horacic aneurysms, and inf ect ious or inf lammat ory
processes.
The postgangl i oni c (thi rd-order) Horner syndrome pat ient may have ipsilat eral
pain and ot her sympt oms suggest ive of clust er or migraine headaches (e. g. ,
t earing, f acial f lushing, rhinorrhea) [196, 507] . Anhidrosis in post ganglionic
Horner syndrome is of t en absent , but because t he sw eat glands of t he f orehead
are supplied by t he t erminal branches of t he int ernal carot id nerve, involvement
of t hese f ibers af t er t hey have separat ed f rom t he remaining f acial sw eat f ibers
may explain t he occurrence of anhidrosis of t he f orehead w it h sparing of t he rest
of t he f ace in t hese pat ient s [542] .
A Horner syndrome may accompany ipsilat eral carot id art ery occlusive disease,
but carot id st enosis may inst ead give rise t o a dilat ed, poorly react ive pupil,
perhaps because of ischemia of t he iris. Di ssecti on of the i nternal caroti d artery
(e. g. , t raumat ic, spont aneous) may result in a Horner syndrome [83, 85, 89, 124,
690] . Biousse et al. , f or example, st udied 146 pat ient s w it h int ernal carot id
art ery dissect ions and f ound t hat 44% (65 of 146) had a painf ul Horner syndrome
t hat w as isolat ed in half of t he cases (32 of 65) [85] . Biousse et al. st at e t hat
“t he associat ion of a t hird-order Horner syndrome
and orbit al and/ or ipsilat eral head pain or neck pain of acut e onset is so
charact erist ic t hat it should be considered diagnost ic of int ernal carot id art ery
dissect ion unless proved ot herw ise” [85] .
Post ganglionic Horner syndrome due t o cavernous sinus lesions (e. g. ,
t hrombosis, inf ect ion, neoplasm) is usually associat ed w it h ot her localizing signs
such as ipsilat eral t hird, f ourt h, or sixt h nerve palsy or t rigeminal nerve
dysf unct ion. I nf lammat ory, neoplast ic, or vascular disease of t he cavernous sinus
may result in ipsilat eral ret ro-orbit al pain and a Horner syndrome (Raeder's
parat rigeminal neuralgia) [303] . O t her causes of a t hird-order Horner syndrome
include inf ect ious or inf lammat ory lesions (e. g. , cervical lymphadenopat hy, ot it is
media, pet rosit is, sphenoid sinus mucocele, herpet ic geniculat e neuralgia,
meningit is, sinusit is), neoplasms (e. g. , cervical node met ast asis, cervical
sympat het ic chain schw annoma or neurolimommas, prolact inoma), syst emic
peripheral, or aut onomic disorders (e. g. , diabet es, amyloidosis, Shy-Drager
syndrome, AI DS), t rauma (e. g. , basilar skull f ract ure), giant cell art erit is, and
Wegener's granulomat osis [94, 271, 323, 377, 572, 604] .
A Horner syndrome t hat alt ernat es f rom one eye t o t he ot her (“al ternati ng”
Horner syndrome) usually over days t o w eeks has been described w it h cervical
cord lesions, syringomyelia, radiat ion myelopat hy, and Shy-Drager syndrome
[ 754] .
A Horner syndrome may be a precursor t o benign t ransient episodes of pupillary
dist ort ion charact erized by peaked elongat ion of t he pupillary apert ure (“tadpol e-
shaped” pupi l ) [773] . This benign phenomenon is likely caused by segment al
spasm of t he iris dilat or muscle and may also occur in pat ient s w it h migraine
and, rarely, in associat ion w it h t onic pupils.
Bilat eral ext reme miosis (“pi npoi nt pupi l s”) may be caused by t he binocular
applicat ion of st rong parasympat homimet ic agent s, pont ine hemorrhage, or t he
use of narcot ics [128] . Unilat eral ext reme miosis suggest s t he use of a st rong
t opical parasympat homimet ic agent [243] .
Parasympathetic Dysfunction
If ani socori a i s present and one of the pupi l s, general l y the l arger one, reacts
poorl y to l i ght, t he diagnosis can be narrow ed t o f our possibilit ies:
1. Pat ient s w it h anisocoria and a poorly react ive pupil should be evaluat ed f or
an ipsilat eral TNP. Nuclear lesions involve bot h eyes. Pupillary irregularit y or
eccent ricit y (sect or palsy of t he iris sphinct er) may result f rom lesions
anyw here along t he t hird nerve or in t he midbrain but not f rom pharmacologic
blockade. Pupillary dilat at ion and unresponsiveness, w it h relat ively
preserved ext raocular muscle f unct ion, is charact erist ic of t he compression
of t he t hird nerve in t he subarachnoid space, usually by t he uncus of t he
t emporal lobe or by an int ernal carot id–post erior communicat ing art ery
aneurysm [436] . Pupillary sparing is t he rule w it h ischemic (e. g. , diabet ic)
oculomot or neuropat hy [565] and may be seen w it h syst emic lupus
eryt hemat osus [663] . Compressive cavernous sinus lesions may spare t he
pupil because t hey of t en involve only t he superior division of t he oculomot or
nerve, w hich carries no pupillomot or f ibers, or t he superior aspect of t he
nerve ant erior t o t he point w here t he pupillomot or f ibers descend in t heir
course near t he I O muscle. Also, t he pupillary sparing may be more apparent
t han real, result ing f rom simult aneous injury t o t he pupillary sphinct er and
dilat or w it h cavernous sinus lesions or f rom aberrant regenerat ion [436] .
Alt hough an ext ra-axial lesion (e. g. , unrupt ured int racranial aneurysm)
compressing t he t hird nerve may cause a dilat ed pupil in isolat ion (or w it h
minimal ocular mot or nerve paresis) [63] , in t he absence of an ext raocular
mot ilit y def icit and/ or pt osis, an isolat ed dilat ed pupil is usually not due t o
t hird nerve paresis. I n addit ion, alt hough int racranial aneurysms, especially
t hose involving t he post erior communicat ing art ery–int ernal carot id art ery
junct ion, of t en produce a f ixed and dilat ed pupil, t his is almost alw ays
associat ed w it h ot her signs of a TNP [529] . Crompt on and Moore report ed
t w o cases of isolat ed pupil dilat ion due t o aneurysm, but t hese pat ient s
developed severe headache and event ual signs of a TNP [165] . Fujiw ara et
al. review ed 26 pat ient s w it h an oculomot or palsy due t o cerebral aneurysm
and report ed t hree w it h only pt osis and anisocoria [255] . G ale and Crockard
observed t ransient unilat eral mydriasis in a pat ient w it h a basilar aneurysm
[ 263] . Miller report ed an isolat ed int ernal opht halmoplegia in a pat ient w it h a
basilar aneurysm [529] . Wilhelm et al. described an oculomot or nerve
paresis due t o a neurinoma of t he t hird nerve t hat began as an isolat ed
int ernal opht halmoplegia in 1979 and t hen developed int o a more t ypical TNP
in 1993 [835] . Kaye-Wilson et al. also described a pat ient w ho init ially had
only minimal pupil signs due t o a neurinoma of t he t hird nerve [401] . A
mydriat ic pupil w as t he present ing sign of a common carot id art ery
dissect ion w it h t he pupil dilat ion preceding ot her signs and sympt oms of a
TNP and cerebral ischemia [440] . How ever, in a pat ient w it h an isolat ed
dilat ed pupil in t he presence of normal ext raocular mot ilit y, a TNP can be
saf ely excluded in almost every circumst ance simply w it h close f ollow -up.
2. Damage t o t he ciliary ganglion or t he short ciliary nerves result s in a toni c
pupi l . I nit ially t here is an isolat ed int ernal opht halmoplegia (a f ixed, dilat ed
pupil w it h loss of accommodat ion), but lat er t here is mydriasis w it h a poor or
absent react ion t o light but a slow const rict ion t o prolonged near eff ort
(l i ght-near di ssoci ati on). Redilat ion af t er const rict ion t o near
st imuli is slow and t onic. Segment al vermif orm movement s of t he iris borders
may be evident on slit lamp examinat ion (due t o sect or palsy of ot her areas
of t he iris sphinct er), and cholinergic supersensit ivit y (see subsequent t ext )
of t he denervat ed iris sphinct er may be demonst rat ed. The vermif orm iris
movement s represent physiologic pupillary unrest or hippus t hat becomes
more impressive because it occurs only in port ions of t he iris in w hich t he iris
sphinct er st ill react s. I n some cases t here is no react ion at all t o light , w it h
t he iris sphinct er palsy being diff use rat her t han segment al.
Tonic pupils are t hought t o be due t o damage of t he ciliary ganglion or short
ciliary nerves w it h subsequent collat eral sprout ing, result ing in t he iris
sphinct er being almost ent irely innervat ed by accommodat ive element s. They
occur f rom local damage t o t he ciliary ganglion or short ciliary nerves, as
part of a w idespread peripheral or aut onomic neuropat hy, or in ot herw ise
healt hy individuals (Adi e's toni c pupi l syndrome) [ 465, 529] . Adie's syndrome
may be unilat eral or bilat eral, is more common in young w omen aged 20 t o
40, and may be associat ed w it h impaired corneal sensat ion and depressed
or absent pat ellar and Achilles t endon ref lexes (t he Holmes-Adie syndrome)
[ 529] . Wit h t ime, ciliary muscle dysf unct ion t ends t o resolve, and t he pupil
becomes progressively miot ic (“l i ttl e ol d Adi e's”). The pupillary light ref lex
does not recover and may w orsen. Some pat ient s may have primary mi oti c
Adie's pupils w it hout passing t hrough a mydriat ic phase [660] . There is a
t endency f or pat ient s w it h unilat eral Adie's syndrome t o develop a t onic pupil
in t he opposit e eye.
A t onic pupil may also be seen w it h hyporef lexia and progressive segment al
hypohidrosis (Ross syndrome) [829] . Bilat eral ciliary ganglion ischemia is
also t he likely cause of t he bilat eral, asymmet ric mydriasis t hat has rarely
been not ed w it h giant cell art erit is [168] . Syphilis (e. g. , t aboparesis) may
produce large pupils t hat are f ixed t o bot h light and near-eff ort ; t heref ore,
pat ient s w it h bilat eral t onic pupils should have serologic t est s f or syphilis
[ 241] .
3. Damage to the i ri s due t o ischemia, t rauma, or an inf lammat ory process may
cause mydriasis. Clinical charact erist ics of suggest ing abnormalit ies of t he
iris st ruct ure as a cause f or mydriasis include: no associat ed pt osis or ocular
mot ilit y dist urbance (vs. TNP); t he pupil is of t en irregular w it h t ears in t he
pupillary margin due t o t ears in t he iris sphinct er (vs. smoot h margin in drug-
relat ed pupillary abnormalit ies); irregular cont ract ion of t he pupil t o light ; t he
event ual development of iris at rophy may occur; and poor or no response of
t he pupil t o 1% pilocarpine.
4. Mydriasis may be induced by t he inst illat ion of a parasympathi col yti c drug
(e. g. , at ropine, scopolamine). Unilat eral mydriasis may f ollow t he use of
t ransdermal scopolamine t o prevent mot ion sickness [146] , t he accident al
inst illat ion int o t he eye of f luids f rom cert ain plant s (e. g. , jimsonw eed) t hat
cont ain belladonna and at ropine-like alkaloids, and exposure t o cert ain
cosmet ics and perf umes.
A caref ul hist ory is usually all t hat is required in pat ient s w it h inadvert ent or
int ent ional (e. g. , glaucoma medicat ion, t reat ment w it h t opical cycloplegics f or
uveit is) exposure t o agent s t hat may aff ect pupil size. I n general, in accident al
pharmacologic pupillary abnormalit ies, a large pupil indicat es increased
sympat het ic t one w it h dilat or st imulat ion (e. g. , ocular decongest ant s, adrenergic
inhalant s in t he int ensive care unit , et c. ) or decreased parasympat het ic t one w it h
sphinct er block (e. g. , Belladonna alkaloids, scopolamine pat ch, ant icholinergic
inhalant s, t opical gent amicin, lidocaine inject ion in orbit , et c. ). Small pupils
indicat e decreased sympat het ic t one or increased parasympat het ic st imulat ion
(e. g. , pilocarpine, glaucoma drops, ant icholinest erases such as f lea or t ick collar
or insect icides [238] ).
Nurses, physicians, and ot her healt h care w orkers are part icularly prone t o
inadvert ent or int ent ional exposure t o pharmacologic mydriat ics. The pupil size of
pat ient s w it h pharmacologic sphinct er blockade is of t en quit e large (>8 mm),
of t en in t he order of 10 t o 12 mm in diamet er, w hich is much great er t han t he
mydriasis usually seen in a t ypical TNP or t onic pupil syndrome. The pupils are
evenly aff ect ed 360 degrees (vs a t onic pupil) and smoot hly aff ect ed around
w it hout irregularit y (vs iris t rauma). Adrenergic pharmacologic mydriasis (e. g. ,
phenylephrine) may be clinically dist inguished by blanched conjunct ival vessels,
residual light react ion, and a ret ract ed upper lid due t o sympat het ic st imulat ion
of t he upper lid ret ract or muscle. Most eye-w hit ening drops (e. g. , oxymet azoline,
phenylephrine) cont ain sympat homimet ics t oo w eak t o dilat e t he pupil unless t he
eye is abraded (e. g. , cont act lens w ear). Wit h adrenergic mydriasis, t he pupil
may react t o bright light due t o t he w orking iris sphinct er muscle, w hich can
overcome dilat or spasm.
Cholinergic supersensit ivit y, w hich is charact erist ic of a t onic pupil, mediat es
pupillary
const rict ion w hen 0. 1% pilocarpine is inst illed. This drug has no eff ect on normal
individuals but causes miosis in t onic pupils. Cholinergic supersensit ivit y of t he
pupil may occasionally occur w it h nonischemic oculomot or nerve palsies and may
be relat ed t o t he degree of preganglionic injury t o t he pupillomot or f ibers [363] .
A st ronger solut ion of pilocarpine (1%) causes const rict ion in t he case of a t hird
nerve lesion but does not modif y pupillary size if t he anisocoria is due t o an
at ropinic drug or t o iris damage. I n t he lat t er case, t he iris may t ransilluminat e,
or it s margin may appear t orn on opht halmoscopy or w hen it is examined w it h t he
slit lamp. Const rict ion af t er t he applicat ion of 1% pilocarpine (af t er f ailing t o
const rict w it h a 0. 1% solut ion) may also occur w it h prior inst illat ion of a
parasympat het ic agent t hat is “w earing off , ” w it h t he use of a sympat homimet ic
agent , or w it h acut e Adie's syndrome [128] . Some pat ient s w it h Adie's syndrome
of recent onset may have a f ixed dilat ed pupil t hat f ails t o const rict t o even a
st rong solut ion (e. g. , 1%) of pilocarpine.
Lepore report ed an unusual case of anisocoria [487] . A w oman present ed w it h
anisocoria, pt osis on t he right , and right -sided headache and neck pain. She w as
f ound t o have Horner syndrome on t he right , an Adie's syndrome on t he lef t , and
f ibromuscular dysplasia.
Argyll-Robertson Pupil
The Argyll-Robert son pupil is charact erist ically seen in pat ient s w it h
neurosyphilis. The pupils are usually involved bilat erally (t hough of t en
asymmet rically) and are miot ic and irregular, w it h variable iris at rophy. A
decreased or absent pupillary light react ion is not ed w it h an int act near response
(l i ght-near di ssoci ati on). Because an eye w it h reduced sensit ivit y t o light (e. g. ,
due t o ret inal or opt ic nerve disease) show s a bet t er response t o near eff ort
t han t o st imulat ion w it h light , t he def init ion of light -near dissociat ion requires
good vision. Because t he near ref l ex (miosis, accommodat ion, and convergence)
has it s supranuclear cont rol t hrough occipit omesencephalic pat hw ays inf luencing
t he pupillary const rict or neurons in t he visceral oculomot or complex by a
diff erent rout e t han t he ret inomesencephalic aff erent s t hat cont rol t he light
ref lex, it may be unaff ect ed by pret ect al lesions t hat int errupt t he pupillary light
ref lex. I ndeed, t he sit e of t he lesion causing Argyll-Robert son pupils is t hought t o
be in t he rost ral midbrain [771] . The miosis is likely due t o t he lesion injuring
supranuclear inhibit ory f ibers t hat aff ect t he visceral oculomot or nuclei.
Li ght-near di ssoci ati on may also be seen w it h midbrain lesions (e. g. , dorsal
midbrain syndrome, encephalit is/ meningit is, Wernicke encephalopat hy and
alcoholism, demyelinat ion, pineal t umors, vascular disease). O t her causes of
light -near dissociat ion include sarcoidosis, diabet es, aberrant regenerat ion of
t he oculomot or nerve, Adie's syndrome, f amilial amyloidosis, paraprot einemic
neuropat hy, syringomyelia, spinocerebellar at axia t ype I , and myot onic dyst rophy
[ 771] . Pat ient s w it h long-st anding diabet es and pat ient s w it h myot onic dyst rophy
may have small, poorly react ive pupils.
The Flynn Phenomenon

I n response t o darkness, t he pupils normally dilat e bilat erally. How ever,
paradoxical const rict ion of t he pupils t o darkness (Fl ynn phenomenon) may
occur in pat ient s w it h congenit al achromat opsia, dominant opt ic at rophy, part ial
Leber's congenit al amaurosis, old bilat eral opt ic neurit is, congenit al nyst agmus,
st rabismus and amblyopia, or congenit al st at ionary night blindness [247] .
Periodic Pupillary Phenomena (Episodic Anisocoria)

The pupil normally exhibit s cont inual, symmet ric, small cont ract ions (hippus).
Periodic pat hologic pupillary movement s (epi sodi c ani socori a) are uncommon
and t hought t o be mediat ed by abnormal parasympat het ic or sympat het ic
act ivit y. Excess parasympat het ic act ivit y may be responsible f or t he periodic
pupillary cont ract ions of cyclic oculomot or palsy [250] , O NM [713] , and t he
rhythmi c pupillary oscillat ions t hat rarely accompany a complet e TNP.
I nt ermit t ent unilat eral mydriasis may occur during or immediat ely f ollow ing a
seizure w it h ipsilat eral or cont ralat eral epilept ic f oci [ 868] , w it h migraine [726,
844] , w it h clust er headache [678] , or as a t ransient phenomena in ot herw ise
healt hy young adult s. Unilat eral pupillary mydriasis associat ed w it h ipsilat eral
visual loss and orbit al or ocular pain may be caused by migraine but may also be
caused by int ermit t ent acut e angle closure glaucoma. An episodic
encephalopat hy w it h dilat ed pupils has been described [379] . Unilat eral ict al
miosis may occur w it h cont ralat eral epilept ic f oci [8] and bilat eral miosis and
int ernal opht halmoplegia has occurred w it h lef t t emporo-occipit al seizure act ivit y
suggest ing irrit at ion of t he cort ical pupillary const rict ive cent er in t his region
[ 662] .
Jacobson report ed 24 pat ient s w it h benign epi sodi c uni l ateral mydri asi s [ 365] .
The median age of t he pat ient s w as 31 years (range, 14 t o 50) and t he median
durat ion of event s w as 12 hours (range, 10 minut es t o 7 days). Associat ed
sympt oms included visual blur, headache,
orbit al pain, monocular phot ophobia, monocular red eye, monocular diplopia, and
monocular posit ional t ransient obscurat ions. Some cases w ere t hought t o be due
t o parasympat het ic insuff iciency of t he iris sphinct er (had associat ed impaired
near vision, impaired accommodat ive f unct ion, and t he anisocoria increased w it h
added ambient light ), w hile ot hers had sympat het ic hyperact ivit y of t he iris
dilat or (associat ed w it h normal near vision and normal react ion of t he pupil
during t he at t ack). No associat ed neurologic disorders w ere f ound in t hese
pat ient s.
I nt ermit t ent sympat het ic nervous syst em pupillary abnormalit ies include cyclic
sympat het ic spasm, in w hich t he pupil dilat es concent rically f or 40 t o 60 seconds
and w hich may occasionally be associat ed w it h lid ret ract ion, f acial
hyperhidrosis, and headache (Cl aude-Bernard syndrome). Pupillary dilat ion may
be rest rict ed t o a segment , giving t he appearance of tadpol e pupi l s [ 773] . O t her
aut onomic abnormalit ies, including Horner syndrome, Adie's pupil, and migraine
are f requent in t hese pat ient s. Pupillary dilat ion, brought about by elevat ion and
st ret ch of t he ipsilat eral arm or leg, has been described as ocul osympatheti c
spasm and may occur w it h lesions of t he C3-C6 segment s of t he spinal cord,
including syringomyelia, t rauma, and inf arct ion [437] . Localized aut onomic hyper-
ref lexia is hypot hesized t o explain t his phenomenon. I nt ermit t ent pupillary dilat ion
may occur ipsilat eral t o a f ront al lobe ast rocyt oma [80] . The t umor may have
irrit at ed t he proposed sympat het ic relays t hat originat e in t he f ront al cort ex or
excit ed t he parasympat het ic inhibit ory relays. I diopat hic alt ernat ing anisocoria
w it hout associat ed signs of oculosympat het ic involvement has also been
described [121] .
Table 8-9 review s pupi l l ary si gns of i mportance i n the i ntensi ve care uni t
set t ing.
Supranuclear Control of Eye M ovements

The complex and precise array of eye movement s t hat secure clear vision result s
f rom t he int eract ion of a number of neural syst ems. Their combined out put plays
on t he ocular mot or nuclei in t he brainst em; t heref ore, t he t erm supranucl ear is
appropriat e t o designat e t hese syst ems. Many eye movement s are involunt ary—
f or example, t he f ine correct ive movement s t hat keep t he eye in t he appropriat e
orbit al posit ion, despit e ongoing head mot ion. I nput f or t hese correct ive
movement s comes f rom t he vest ibular nuclei (VN vest ibular syst em) or f rom t he
ret ina (opt okinet ic and smoot h pursuit syst ems). The syst ems t hat permit a
moving t arget t o remain sharply f ocused in t he f ovea (smoot h pursuit and

vergence syst ems) are also largely involunt ary, alt hough t he person may choose
t o glance or not t o glance at a part icular object . The syst em t hat produces
volunt ary eye movement s is called t he saccadi c system.
TABLE 8-9 Pupillary Signs in the Intensive Care Unit
Unilateral Large Poorly Reactive Pupil

Third nerve palsy
Contusion of eye
Accidental Exposure to Aerosolized Anticholinergics
or
Spilling of Atropine Droplets During Preparation of the
Syringe
Transient (ipsilateral or contralateral) during focal
seizure
or as part of petit mal
Oval Unilateral Nonreactive Pupil—Transitory
Appearance in Brain Death
Bilateral Mydriasis with Normal Reaction to Light
Anxiety, delirium, pain
Episodic encephalopathy with dilated pupils (also
associated with hyperthermia and tachycardia)
During Seizure
Botulism
Drugs–systemic atropine, aerosolized albuterol,
amylnitrate, magnesium sulfate, norepinephrine,
dopamine, aminoglycoside, polypeptide, tetracycline
overdose
Bilateral Midposition and Fixed to Light— Brain Death
Unilateral Small, Reactive— Horner Syndrome
Traumatic carotid dissection
Brachial plexopathy
Internal jugular vein catheterization
Extensive thoracic surgery
Spastic miosis in acute corneal penetration injury
Bilateral Miosis (reaction present but may be difficult to
see even with magnifying glass)
Narcotic agents (e.g., morphine)
Any metabolic encephalopathy
Respiratory distress with hypercapnia and tachypnea
Bilateral Pinpoint, Reactive
Acute pontine lesion, especially hemorrhage
Nonketotic hyperglycemia
(Adapted from W ijdicks EFM. Neurology of critical

illness. Philadelphia, PA: FA Davis Co, 1995).
The Vestibular System

To be clearly perceived, images of t he out side w orld have t o slide over t he ret ina
at a speed of no more t han a f ew degrees per second. O t herw ise, t hings w ould
appear blurry and f uzzy, like a phot ograph t aken w it h a low shut t er speed w hile
t he camera is moving. Wit hout t he appropriat e correct ive syst em, somet hing
similar w ould happen t o t he eye, anchored in t he orbit and const ant ly jerked by
manif old head movement s. The vest ibular syst em drives t he eye w it h t he same
velocit y but in a direct ion opposit e t o t he disrupt ive head mot ion. Theref ore, t he
eye globe, like a gyroscope, keeps it s st able posit ion despit e orbit al
movement s. The VN basically coordinat e t he st abilizat ion of gaze and post ure
and cont ribut e t o t he percept ion of vert icalit y and self -mot ion [304, 475, 480] .
The Vestibulo-ocular Reflex

The ref lex by w hich t he vest ibular syst em perceives head movement and makes
t he eyeball move in t he opposit e direct ion is called t he vesti bul o-ocul ar ref l ex.
Labyrinth and Vestibular Nucleus

The sensory arc of t he ref lex begins at t he semicircular canals (SCCs) of t he
inner ear. Each of t he t hree (horizont al, ant erior, and post erior) SCCs is
st imulat ed by movement s in it s plane and also induces eye movement s in it s
plane (Fl ouren's l aw). The corresponding SCCs of bot h ears are yoked in such a
w ay t hat w hen t he head rot at es, one canal increases it s rat e of f iring w hile t he
corresponding canal in t he opposit e ear slow s it s rat e. The impulses t ravel by
w ay of t he vest ibular nerve t o t he ipsilat eral vest ibular nuclear complex in t he
pont omedullary junct ion. Fibers f rom t he ampullae of t he SCCs t erminat e
primarily in t he superior nucleus and rost ral part of t he medial nucleus, w hereas
f ibers f rom t he ut ricular macula end predominant ly in t he lat eral nucleus, w it h
some f ibers also going t o t he medial and descending nuclei. When a vest ibular
nucleus is excit ed, it t ends t o deviat e t he eyes t ow ard t he cont ralat eral side.
How ever, each vest ibular nuclear complex has neurons t hat increase t heir rat e of
f iring w it h ipsilat eral head rot at ions and ot hers t hat increase t heir discharge rat e
w it h cont ralat eral rot at ions. This f eat ure, coupled w it h t he exist ence of a
vest ibular commissure in t he vicinit y of t he VN, may explain w hy vest ibular
f unct ion recovers w hen one side is damaged. From t he vest ibular nucleus, t he
signal f or horizont al eye movement s is relayed t o t he abducens nucleus in t he
cont ralat eral side of t he low er pons. Vest ibular nucleus neurons project not only
t o mot or neurons but also send collat erals t o t he nucleus proposit us hypoglossi
and t he cell groups of t he paramedian t ract s (PMT). The nucleus proposit us
hypoglossi and t he adjacent medial vest ibular nucleus (MVN) make up t he neural
i ntegrator, w hich is crucial f or gaze holding; t he paramedian t ract cells relay
inf ormat ion about eye movement s t o t he cerebellar f locculus.
Ocular Motor Nuclei, the Medial Longitudinal

Fasciculus, and Vestibular Pathways
The abducens nucleus has t w o t ypes of int ermingled neurons: mot or neurons and
int ernuclear neurons. The axons of t he int ernuclear neurons cross t o t he
cont ralat eral side in t he low er pons and, af t er ascending in t he MLF, synapse in
t he port ion of t he oculomot or nucleus t hat innervat es t he MR (Fig. 8-12).
Theref ore, a horizont al vest ibulo-ocular impulse originat ing in t he horizont al canal
is relayed f rom t he ipsilat eral MVN t o t he cont ralat eral abducens and t he
ipsilat eral MR subnuclei neurons, result ing in deviat ion of t he eyes t o t he
cont ralat eral side. There is also a direct pat hw ay f rom t he VN t o t he ipsilat eral
MR subnucleus t hrough t he ascending t ract of Deit ers, w hich lies lat eral t o t he
MLF. The clinical signif icance of t his pat hw ay is unclear. Similar pat hw ays
(medial and superior) mediat e vert ical vest ibular eye movement s. Excit at ory
impulses f rom t he vest ibular nucleus cross in t he brainst em and ascend in t he
MLF (f or t he post erior canal project ion) and in t he brachium conjunct ivum, MLF,
and vent ral t egment al pat hw ay (f or t he ant erior canal project ion), synapsing in
t he areas of t he t rochlear or oculomot or nuclei w here t he muscles involved in t he
appropriat e movement are represent ed (Fig. 8-12). I nhibit ory project ions f rom
t he same canals ascend ipsilat erally in t he MLF t o synapse in ocular mot or
subnuclei t hat mediat e relaxat ion of ant agonist muscles. St imulat ion of t he
ant erior canal (e. g. , by dow nw ard head accelerat ion) excit es t he ipsilat eral SR
muscle and t he cont ralat eral I O muscle, w hereas st imulat ion of t he post erior
canal (e. g. , by upw ard head accelerat ion) excit es t he ipsilat eral SO muscle and
t he cont ralat eral I R muscle. Theref ore, lesions of t he MLF cause int ernuclear
opht halmoplegia and also impair t he vert ical vest ibulo-ocular ref lex.
FI G URE 8-12 Vest ibulo-ocular pat hw ays. A: Ant erior canal excit at ory
pat hw ays; B: Post erior canal excit at ory pat hw ays; C: Horizont al canal
excit at ory pat hw ays.
The connect ions f rom t he ant erior and post erior SCCs also cont act t he nucleus
of Cajal, w hich is import ant in eye–head coordinat ion in roll and in vert ical gaze
holding, and t he riMLF, w hich is import ant in generat ing quick phases of
vest ibular nyst agmus in t he vert ical and t orsional planes [475] . Vest ibular nuclear
out put also project s t o t he spinal cord, t o generat e vest ibulospinal ref lexes, and
t o t he t halamus and cerebral cort ex, t o provide input s f or percept ion of
movement . Theref ore, t he vest ibulo-ocular ref lex pat hw ays also mediat e post ure
and percept ion [475] .
Head Position
I n addit ion t o inf ormat ion about angular accelerat ion regist ered by t he SCCs, t he
labyrint h provides inf ormat ion about t he st at ic posit ion of t he head. This is
regist ered by t he ut ricle and t he saccule, sit uat ed on planes perpendicular t o
each ot her, and reaches t he ext raocular muscles t hrough pat hw ays akin t o t he
ones used by signals f rom t he SCCs (Fig. 8-13). The ut ricle and saccule project
predominant ly t o t he lat eral (Deit er's) vest ibular nucleus, alt hough t here are
some superior nucleus project ions. I psilat eral (probably inhibit ory) ocular mot or
connect ions t ravel over t he ascending t ract of Deit er's, w hereas cont ralat eral
connect ions t ravel in t he MLF.
Linear or t ranslat ional movement s of t he head (e. g. , t he up-and-dow n
movement s w it h running) are det ect ed by t he ot olit h organs by virt ue of t heir
sensit ivit y t o linear accelerat ion [480] . The ot olit hs t heref ore subserve t he
t ranslat ional vest ibulo-ocular ref lex (TVO R), w hich has a lat ency of less t han 35
milliseconds. Lat eral head t ilt (roll) induces some ocular count er-rolling, but t his
amount s t o only 10% of t he head t ilt in humans.
Caloric Testing, Nystagmus

The slow eye mot ions induced by t he vest ibular syst em cannot be appreciat ed in
ordinary condit ions. They become quit e obvious, how ever, if t here is a pat hologic
imbalance bet w een t he VN. Such imbalance can be produced by inst illing a f ew
millilit ers of cold w at er in t he ext ernal audit ory canal w hile t he head is kept at a
30-degree angle w it h t he horizont al plane. This result s in a slow ing of t he f iring
rat e of t he horizont al SCC on t he side of t he inf usion. Consequent ly, t he eyes
t end t o deviat e slow ly t o w here t he cold w at er has been inf used. How ever, quick
correct ive jerks in a direct ion opposit e t he slow mot ion keep t he eyes looking in
t he direct ion w illed by t he individual w ho is alert . The result ant rhyt hmic eye
movement w it h slow and quick component s in opposit e direct ions is t ermed
nystagmus. I n a comat ose pat ient , t he quick jerks are absent and t he eyes
remain deviat ed t ow ard t he side t hat has been cooled f or 10 t o 25 seconds.
Test ing of pat ient s w it h vest ibular sympt oms should include st imuli corresponding
t o t he rot at ional head pert urbat ions t hat occur during locomot ion. Some pat ient s
w it h bilat eral vest ibular dysf unct ion may have st able gaze w hile sit t ing or
st anding but develop impaired vision and oscillopsia during w alking because of
excessive mot ion of images on t he ret ina due t o t he f ailure of t he normal
vest ibulo-ocular ref lex.
FI G URE 8-13 Diagram show ing ut ricular pat hw ays. CN = crani al nerve; MLF
= medi al longit udinal f asciculus. (From Brazis PW. O cular mot or
abnormalit ies in Wallenberg's lat eral medullary syndrome. Mayo Cl i n Proc
1992; 67: 365, Reprint ed w it h permission. )
Full-Field Optokinetic Reflex

The vest ibulo-ocular ref lex becomes f at igued af t er about 30 seconds. A diff erent
syst em is required t o maint ain t he eyes on t arget during prolonged head mot ion
in t he same direct ion. The int ermediat e pat hw ay probably includes ret inal
project ions t o t he nucleus of t he opt ic t ract (NO T) and accessory opt ic syst em
(AO S) w hich, in t urn, project t o t he pont ine nuclei, t he vest ibular syst em, and,
t hrough t he inf erior olive, t o t he vest ibulocerebellum. The slow eye movement
t ends t o st abilize t he image. This is t he so-called opt okinet ic ref lex t hat requires
t hat t he moving object f ill most of t he visual f ield (f ull-f ield st imulat ion) and
diff ers f rom t he smoot h pursuit of a t arget t hat is being f ollow ed w hile it is
project ed in t he macular region of t he ret ina. I n humans, smoot h pursuit probably
plays a great er role t han t he f ull-f ield opt okinet ic ref lex in st abilizing images in
t he ret ina. How ever, w hen t he pat hw ay t hat mediat es pursuit (see Smoot h
Pursuit Syst em) is damaged, t he more primit ive f ull-f ield pursuit mechanism can
be elicit ed. Unlike f oveal pursuit , f ull-f ield pursuit builds up slow ly (10 t o 20
seconds) and decays gradually af t er t he st imulus is t erminat ed (opt okinet ic
af t er-nyst agmus). Theref ore, t he opt okinet ic syst em act s as a vel oci ty storage
mechanism. O pt okinet ic st imulat ion may induce a compelling sensat ion of self -
rot at ion called ci rcul ar vecti on t hat develops even t hough no peripheral
vest ibular st imulat ion has occurred.
Lesions of t he ant erior visual pat hw ays decrease opt okinet ic responses.
Unilat eral vest ibular lesions cause a direct ional preponderance of opt okinet ic
nyst agmus, w it h increased slow -phase velocit y t ow ard t he side of t he lesion.
Reversed opt okinet ic nyst agmus is charact erist ically f ound in pat ient s w it h
benign congenit al nyst agmus (see subsequent t ext ). I n t his case, t he quick
component beat s in t he direct ion of t he slow ly moving opt okinet ic t arget . This
act ually represent s t he pat ient 's ow n gaze-modulat ed spont aneous nyst agmus
shif t ed t o t he primary posit ion of gaze by opt okinet ic st imulat ion.
Smooth Pursuit System

An object is seen w it h most det ail w hen it s image f alls in t he f ovea, locat ed in
t he post erior pole of t he ret ina. Tw o ocular mot or syst ems allow visual images t o
remain in t he f ovea: smoot h pursuit , as t he object moves vert ically or
horizont ally,
and vergence eye movement s (convergence and divergence) as t he object moves

along t he dept h axis of t he visual f ield, part icularly as it approaches t he subject .
I mages moving aw ay f rom t he f ovea const it ut e t he st rongest st imuli f or smoot h
pursuit . At t he bedside, handheld opt okinet ic drums or t apes provide an
adequat e st imulus f or t he f oveal-pursuit syst em. The smoot h pursuit syst em
cannot f ollow object s t hat move f ast er t han 30 t o 40 degrees per second, t he
low er range being more charact erist ic of elderly persons. Fast er-moving object s
elicit quicker eye movement s, t ermed saccades. Saccades are under t he cont rol
of t he w ill, but smoot h eye movement s cannot be volunt arily produced and need
a visual object t o be t raced. When a person t ries t o move t he eyes slow ly, a
number of short quick saccades result . How ever, some individuals can elicit slow
smoot h eye movement s by t racking t heir ow n slow ly moving f inger in darkness.
As an object of int erest moves in f ront of t he subject , bot h t he head and t he
eyes may t urn t o keep it in t he macula. To do t his, how ever, t he vest ibulo-ocular
ref lex, discussed in t he preceding t ext , must be inhibit ed. O t herw ise, as t he
head moves in t he direct ion of t he object , t he eyes w ould be pulled in t he
opposit e direct ion. The neural command f or t he head and eyes t o f ollow an
object inhibit s t he vest ibulo-ocular ref lex at t he same t ime. Theref ore,
abnormalit ies of t he pursuit syst em may be expressed by an inabilit y t o inhibit
t he vest ibulo-ocular ref lex.
The smoot h pursuit syst em may be t est ed by having t he pat ient t rack a small
moving t arget smoot hly in a horizont al and vert ical direct ion [480] . An opt okinet ic
drum or t ape may also be used t o induce smoot h pursuit eye movement s.
Anatomy of the Pursuit System

The anat omic pat hw ays involved in t he smoot h pursuit syst em are complex [480,
794] (Fig. 8-14). I n monkeys, t he sensory syst em includes a project ion f rom t he
dorsolat eral geniculat e nucleus t o t he st riat e cort ex, w hich t hen sends f ibers t o
t he middle t emporal (MT) visual area. Area MT processes inf ormat ion about t he
speed and direct ion of t arget mot ion in t he cont ralat eral visual f ield and sends
t his inf ormat ion t hrough an arcuat e f iber bundle t o t he adjacent medial superior
t emporal (MST) area. Area MT project s cont ralat erally t hrough t he t apet um,
major f orceps, and splenium of t he corpus callosum t o t he areas MT and MST of
t he cont ralat eral hemisphere. Area MST combines an int ernal signal of eye
velocit y w it h t he mot ion signal f rom area MT. The homologues of t he areas MT
and MST in humans are probably locat ed in t he lat eral occipit al cort ex (area 19)
and t he adjacent vent rocaudal aspect of Brodmann's area 39 (w hich corresponds
t o t he angular gyrus) [546] . Bot h areas MT and MST project t hrough arcuat e
f iber bundles t o t he post erior pariet al cort ex (PPC) in t he vent ral bank of t he
int rapariet al sulcus, w hich is concerned w it h attenti on t o moving object s. Areas
MT, MST, and t he PPC all project t o t he f ront al eye f ields (FEFs) (FEF;
Brodmann's area 8).
Ret inal inf ormat ion on t he speed and direct ion of a moving t arget is abst ract ed in
t he visual cort ex, especially areas MT and MST. Such processing t akes int o
account current eye movement s, encodes t he direct ion and speed of complex
moving st imuli, and allow s f or t he eff ect s of relat ive mot ion of t he background
during pursuit . These signals are passed on t o t he f ront al areas, w hich may
cont ribut e predict ive propert ies t o t he pursuit response.
Descending pursuit pat hw ays run ipsilat erally f rom areas MT and MST t hrough
t he int ernal sagit t al st rat um (along t he lat eral surf ace of t he lat eral vent ricle),
t he ret rolent icular int ernal capsule–I nt ernal Capsule (I C), and t he post erior
cerebral peduncle t o t erminat e in t he dorsolat eral and lat eral pont ine nuclei–
Dorsolat eral and Lat eral Pont ine Nuclei (DLPN). Anot her mot or pat hw ay project s
f rom t he FEFs t hrough t he I C and medial port ion of t he cerebral peduncle t o t he
dorsolat eral pont ine nuclei. The FEFs generat e vol i ti onal pursuit , w hich does not
necessarily rely on a moving visual st imulus (e. g. , predict ive smoot h pursuit or
pursuit of a moving t arget t hat t ransient ly disappears). Area MST generat es
ref l exi ve pursuit , in w hich a moving visual st imulus is alw ays required t o elicit
pursuit .
For hori zontal pursui t, t he lef t mot or syst em mediat es smoot h pursuit eye
movement s t o t he lef t , w hile t he right mot or syst em mediat es movement s t o t he
right . The pat hw ay decussat es t w ice at t he pont ocerebellar level. Pont ine nuclei
on t he side t ow ard w hich t he eyes move send, t hrough t he middle cerebellar
peduncle, excit at ory mossy f ibers t o granule cells of t he cont ralat eral cerebellar
cort ex, including t he f locculus, paraf locculus, uvula, and post erior vermis (lobules
VI -VI I ). The granule cells excit e basket cells and st ellat e cells, w hich in t urn
inhibit Purkinje cells t hat send inhibit ory project ions t o t he ipsilat eral MVN.
Excit at ory project ions f rom t he vest ibular nucleus cross t he midline in t he angular
bundle of Low y, adjacent t o t he f ourt h vent ricle, ending in t he opposit e abducens
nucleus [387, 480, 704] . The
paramedian pont ine ret icular f ormat ion–Paramedian Pont ine Ret icular Format ion
(PPRF) is probably not involved in smoot h pursuit eye movement s.
FI G URE 8-14 Schemat ic diagram illust rat ing major pat hw ays involved in
smoot h pursuit eye movement s. MT = middle t emporal area; MST = medial
superior t emporal area; FEF = f ront al eye f ield; DLPN = dorsolat eral pont ine
nucleus; VN = vest ibular nucleus.
Verti cal pursui t signals f ollow a similar course and, af t er synapsing in t he VN,
project rost rally t hrough t he MLF and brachium conjunct ivum [618, 642] and
probably t raverse t he I NC. Upw ard pursuit pat hw ays are believed t o decussat e
in t he post erior commissure (PC), as PC lesions abolish upw ard pursuit , bef ore
ending in t he appropriat e ocular mot or nuclei. Dow nw ard pursuit f ibers likely
descend af t er reaching t he I NC and do not t raverse t he PC. Upw ard and
dow nw ard smoot h pursuit may be rest rict ed by unilat eral midbrain lesions.
The cerebellum plays an import ant role in synt hesizing t he pursuit signal f rom
visual and ocular mot or input s. The dorsal vermis and f ast igial nucleus may
cont ribut e mainly t o t he onset of pursuit , w hile t he paraf locculus and f locculus
mainly sust ain t he pursuit response.
There is also anot her pat hw ay concerned w it h smoot h pursuit t hrough t he AO S
and t he NO T [480] . The AO S is composed of a group of midbrain nuclei t hat
receives input s mainly f rom t he cont ralat eral ret ina t hrough t he accessory opt ic
t ract . The AO S project s t o t he inf erior olive and t o t he nucleus preposit us
hypoglossi–medial vest ibular nucleus–Nucleus Preposit us Hypoglossi–Medial
Vest ibular Nucleus (NPH-MVN) complex. The NO T is a pret ect al nucleus lying in
t he brachium of t he SC f rom w hich it receives ret inal input s. I t project s t o
pont ine nuclei, including DLPN and NRTP (nucleus ret icularis t egment i pont is–
Nucleus Ret icularis Tegment i Pont is), and t he inf erior olive, w hich, in t urn,
project s t o t he cerebellum. The AO S and NO T may play a role in act ivat ing t he
t ranscort ical-pont ine-cerebellar pursuit pat hw ay.
Lesions Affecting Smooth Pursuit

Smoot h pursuit abnormalit ies occur w it h lesions anyw here along t he course of
smoot h pursuit pat hw ays [481] . Front al lesions may impair
ipsilat eral smoot h pursuit , especially t o t arget s moving in a predict able pat t ern
[ 547, 654] . Bilat eral occipit al lesions abolish smoot h pursuit . Pariet al lesions
decrease t he amplit ude and velocit y of smoot h pursuit t ow ard t he side of t he
lesion [479] . This def icit is most evident af t er hemispherect omy. Tw o dist inct
def icit s of visual t racking f or unpredict able st imuli have been described w it h
unilat eral post erior cerebral cort ex lesions [473, 775] . The f irst is a
unidirect ional def icit of smoot h pursuit f or t arget s moving t ow ard t he side of t he
lesion, in response t o st imuli present ed int o eit her visual hemif ield. The second
def icit is a bidirect ional inabilit y t o est imat e t he speed of a moving t arget in t he
visual hemif ield cont ralat eral t o t he lesion, causing inaccurat e saccades t o
moving t arget s and impaired smoot h pursuit init iat ion. These t w o def icit s of
visual t racking are similar t o t hose described in monkeys w it h lesions of t he MST
and MT visual areas, respect ively. Pat ient s w it h ret inot opic and direct ional
def icit s of smoot h pursuit have lesions near t he junct ion of Brodmann's areas 19,
37, and 39, providing evidence t hat t his region includes t he human homologues of
monkey areas MT and MST [71, 546] .
Lesions occurring in a band ext ending f rom t he occipit ot emporal areas
post eriorly, t hrough t he int ernal sagit t al st rat um, t he post erior and ant erior limbs
of t he I C w it h adjacent st riat um, t o t he dorsomedial f ront al cort ex ant eriorly
cause predominant ly ipsilesional pursuit def icit s [481] . Post erior t halamic
hemorrhage may cause a def icit in smoot h pursuit t ow ard t he side of t he lesion
by int errupt ing cort icof ugal f ibers passing t o t he pont ine nuclei near t he post erior
t halamus or t he adjacent ret rolent icular port ion of t he I C [120] . This pursuit
def ect may be associat ed w it h hypomet ric saccades aw ay f rom t he side of t he
lesion due t o associat ed disrupt ion of t he dorsal t ranst halamic pat hw ay or t he
int ermediat e pat hw ay mediat ing saccadic eye movement s, or bot h.
Because of t he double decussat ion in t he brainst em of t he mot or pursuit
pat hw ays, pat ient s w it h post erior f ossa lesions may have impaired ocular smoot h
pursuit eit her cont ralat erally or ipsilat erally [262, 387] . Unilat eral midbrain
lesions may result in ipsilat eral pursuit def ect s [398, 861] as may basal pont ine
lesions t hat damage t he pont ine nuclei [277, 381, 398, 760, 823] . MLF lesions
may dist urb vert ical smoot h pursuit . Unilat eral pont ine or rost ral medulla lesions
may slow dow n cont ralat eral smoot h pursuit more t han ipsilat eral pursuit w hile
sparing t he vest ibulo-ocular ref lex [387] . Theref ore, lesions of t he pont ine
t egment um t hat paralyze ipsilat eral saccades can spare t he vest ibulo-ocular
ref lex, and smoot h pursuit movement and t he vest ibulo-ocular ref lex can be
impaired independent ly by pont ine or medullary lesions.
The cerebellar f locculus and vermis play an import ant role in t he product ion of
smoot h pursuit [826] . The f locculus probably maint ains pursuit during st eady
st at e t racking, w hereas t he vermis may be more import ant w hen t arget velocit y
is changing [480] . Unilat eral cerebellar damage result s in t ransient impairment of
pursuit in t he direct ion of t he involved side [823] , w hereas bilat eral damage
causes permanent impairment of smoot h pursuit eye movement s. A post erior
vermal lesion may impair pursuit [609] , and middle cerebellar peduncle lesions or
f loccular lesions may cause an ipsilat eral pursuit def ect [398, 823] .
The f unct ioning of t he smoot h pursuit syst em depends on t he degree of at t ent ion
elicit ed by t he object being f ollow ed. Many drugs impair smoot h pursuit ,
rendering it jerky or slow or abolishing it alt oget her. Pursuit gain is decreased
w it h cert ain disseminat ed disorders, such as progressive supranuclear palsy–
Progressive Supranuclear Palsy (PSP) [249, 506] , Hunt ingt on's disease,
G erst mann-St raussler-Scheinker disease [852] , and human immunodef iciency
virus (HI V)-relat ed illnesses [523] .
Pat ient s w it h lesions t hat impair pursuit are of t en unable t o inhibit t he vest ibulo-
ocular ref lex. For inst ance, a pat ient w it h a lef t hemispherect omy, result ing in
impaired pursuit t o t he lef t , f ollow ed smoot hly an object t urning t o t he right along
w it h him. When rot at ing t o t he lef t , how ever, he had t o make quick ref ixat ions t o
cat ch up w it h t he t arget because t he vest ibulo-ocular ref lex t hat in t his sit uat ion
t ends t o deviat e t he eyes t o t he right w as not properly compensat ed f or by
f oveal f ixat ion and smoot h pursuit . I nadequat e suppression of t he vest ibulo-
ocular ref lex can be easily assessed by looking f or quick ref ixat ions as t he
pat ient gazes at a f inger in his out st ret ched arm w hile he is being rot at ed in a
w heelchair.
The Saccadic System

Most obvious among t he eye movement s are t he quick ref ixat ions called
saccades. Their purpose is t o place in t he f ovea object s of int erest , w hich of t en
have f irst been regist ered by t he peripheral ret ina. Saccadic eye movement s are
also used t o inspect a complex scene, such as a paint ing. A f airly complicat ed
array of short ref ixat ions t hen t akes place, as t he diverse det ails of t he paint ing
are calibrat ed by placing t hem successively in t he macular region. I n addit ion t o
t hese t ypes of saccades, a person may produce saccades at w ill or on command
(volit ional saccades) and can inhibit
t he t endency t o glance at an object perceived by t he peripheral ret ina. O t her
t ypes of saccadic eye movement s include t he quick, correct ive phase of
vest ibular and opt okinet ic nyst agmus. O n a command such as “look t o your
right , ” saccades are produced w it h great er ease if t he head as w ell as t he eyes
are t urned in t he appropriat e direct ion. Turning t he eyes w hile keeping t he head
st ill is somew hat more diff icult .
Saccades are of several t ypes, as f ollow s [616] :
1. Ref l exi ve saccades are ext ernally t riggered by t he sudden appearance of a

visual t arget on t he peripheral part of ret ina (ref lexive visually guided
saccades) or a sudden noise in t he immediat e environment (ref lexive audit ory
saccades).
2. Intenti onal saccades are int ernally t riggered w it h a goal. These saccades
may be visually guided (goal t o cat ch on t he f ovea a t arget t hat has been
visible on t he peripheral part of t he ret ina), predict ive (goal t o f ind t he image
of a t arget not yet or no longer visible w hen t he image is expect ed at a
specif ic locat ion), or memory-guided (t ow ard t he remembered posit ion of a
t arget perceived a moment bef ore on t he peripheral part of t he ret ina or
t ow ard t he remembered posit ion t o w hich gaze w as direct ed bef ore a body
rot at ion).
3. Anti saccades are made in direct ion opposit e t o a suddenly appearing lat eral
visual t arget (also int ent ional).
4. Spontaneous saccades are int ernally t riggered but w it hout a goal and occur
during anot her mot or act ivit y (such as speech) or at rest in darkness.
Alert ness is required f or t he product ion of saccades. The slow phase of t he

vest ibulo-ocular ref lex can be elicit ed in a comat ose pat ient by t he doll's head
maneuver or by caloric st imulat ion. The eyes are t hen slow ly driven by t he
vest ibular ref lex, but t here are no correct ive saccadic jerks.
Mechanical Properties of Saccadic Eye Movements

Saccades are produced by a combinat ion of t w o mechanical element s: (a) a
pul se (a velocit y command), w hich, overcoming t he resist ance of t he orbit al
t issues and t he inert ia of t he globe, changes t he posit ion of t he eye in t he orbit ,
and (b) a step (a posit ion command) or change in t onic cont ract ion of t he orbit al
muscles, w hich, overcoming t he elast icit y of t he orbit al t issues, keeps t he eye in
t he new posit ion. A great er eff ort is required t o keep t he eye in a more eccent ric
posit ion. The t ransit ion bet w een t he end of t he pulse and t he beginning of t he
st ep is act ually not abrupt but gradual (act ually a pul se-sl i de-step).
A subject asked t o sw it ch his gaze f rom one object t o anot her produces
saccades of larger amplit ude w hen t he object s are f art her apart . The amplit ude
of t he saccade is expressed by t he degrees of t he angle it subt ends. The
velocit y of a saccade is expressed in degrees per second. There is an invariat e
relat ion bet w een t he size and t he peak velocit y of saccades. Larger
displacement s in t he orbit require f ast er saccades.
Saccades subt ending a f ew degrees have velocit ies as low as 100 degrees per
second, w hereas large ref ixat ions may reach peak velocit ies of 700 degrees per
second. Elderly subject s and t hose w ho are drow sy, inat t ent ive, or medicat ed
produce slow er saccadic eye movement s. The predict abilit y of t he t arget , as in a
t est sit uat ion in w hich t he subject looks alt ernat ely at eit her of t w o t arget s,
increases velocit y. Follow ing t he signal t o sw it ch gaze, t here is a lat ency of
about 200 milliseconds bef ore t he saccade t akes place.
I n t he product ion of saccades, t he brain apparent ly makes use of a sensory map
of t he visual environment and of t he coordinat es of t he orbit . The neural
mechanisms involved in t he product ion of saccades compare t he ocular posit ion
desired w it h t he act ual posit ion and calculat e t he pulse and st ep t o be generat ed
t o reach t he desired posit ion. Disease of t hese neural mechanisms result s in
saccades t hat have an abnormal velocit y or erroneous amplit ude (dysmet ria) or
f ail t o keep t he eye st eady in t he desired posit ion.
During saccades t he visual f ield sw eeps across t he ret ina at high velocit y, and
concomit ant visual blur is prevent ed by saccadic omission in w hich percept ion
during t he saccade is reduced by t he presence of a preceding and f ollow ing
st at ionary background (visual masking) [125] . A cent ral inhibit ory mechanism
may underlie t his saccadic omission [125] .
Anatomy of the Saccadic System

Tw o t ypes of neurons play an import ant role in t he generat ion of saccades: burst
neurons and omnipause neurons. Excit at ory burst neurons–Excit at ory Burst
Neurons (EBNs) are locat ed in t he PPRF and lie rost ral t o t he abducens nucleus
in t he dorsomedial nucleus ret icularis pont is caudalis–Nucleus Ret icularis Pont is
Caudalis (NRPC). EBNs project t he excit at ory pulse t o t he ipsilat eral abducens
nucleus (t o bot h abducens mot oneurons and int ernuclear neurons) t hat result s in
horizont al saccades. The st ep of innervat ion at t he end of t he saccade arises
f orm t he NPH and MVN t hat make up t he neural
i ntegrator f or horizont al gaze. I nhibit ory burst neurons–I nhibit ory Burst Neurons
(I BNs) f or horizont al saccades lie caudal t o t he abducens nucleus in t he nucleus
paragigant ocellularis dorsalis in t he dorsomedial port ion of t he rost ral medulla.
The I BNs send axons t o t he cont ralat eral abducens nucleus t o inhibit t his nucleus
during ipsilat eral saccades. The I BNs silence t he act ivit y in t he ant agonist
muscles (cont ralat eral lat eral rect us and ipsilat eral MR) during horizont al
ipsilat eral saccades.
FI G URE 8-15 Schemat ic diagram illust rat ing t he supranuclear pat hw ays f or
lat eral visually guided saccades. + = excit at ory; - = inhibit ory; ? = unknow n
eff ect (Adapt ed f rom Pierrot -Deseilligny C, Rivaud S, Penet C, et al.
Lat encies of visually guided saccades in unilat eral hemispheric cerebral
lesions. Ann Neurol 1987; 21: 138 ; Pierrot -Deseilligny C, Rivaud S, Fournier
E, et al. Lat eral visually guided saccades in progressive supranuclear palsy.
Brai n 1989; 122: 471. )
The PPRF, locat ed ant erior and lat eral t o t he MLF, ext ends f rom t he
pont omesencephalic junct ion t o t he abducens nucleus. I mpulses f rom t he FEFs
are relayed t o t he pont ine PPRF, w hich coordinat es bot h vert ical and horizont al
saccades (t he rost ral PPRF probably coordinat es horizont al saccades, w hereas
t he caudal PPRF may play an import ant role in t he generat ion of vert ical as w ell
as horizont al saccades). Signals f or horizont al saccades proceed f rom t he
ipsilat eral PPRF in t he low er pons t o t he ipsilat eral abducens nucleus and
cont ralat eral oculomot or nucleus t hrough t he MLF. Theref ore, t he PPRF mediat es
a saccade t o t he same side of t he pons but cont ralat eral t o t he f ront al eye f ield
t hat originat ed t he chain of command (Fig. 8-15).
The EBNs and I BNs f or vert ical and t orsional saccades are int ermingled in t he
midbrain in t he ri MLF, locat ed in t he prerubral f ield of t he vent ral
diencephalomesencephalic junct ion, rost ral t o t he t ract us ret rof lexus. Each riMLF
cont ains neurons t hat burst f or upw ard and dow nw ard saccades, but f or
t orsional quick phases in one direct ion only (t he right riMLF is responsible f or
t he right eye ext ort ing and t he lef t eye int ort ing, w hile t he lef t riMLF is
responsible f or t he lef t eye ext ort ing and t he right eye int ort ing) [82] . Theref ore,
an riMLF lesion w ill result in cont ralesional t orsional deviat ion [129] . Project ions
f rom t he riMLF t o mot orneurons innervat ing t he elevat or muscles are bilat eral,
w it h axon collat erals probably crossing t o t he opposit e side at t he level of t he
mot orneurons axons (crossing w it hin t he oculomot or nucleus) and not in t he PC
[ 82] . Axons f rom t he riMLF f or depressor muscles are unilat eral; t heref ore,
unilat eral lesions of t he
riMLF w ill slow dow nw ard saccades but spare upw ard saccades.
Axons f rom t he riMLF send collat erals t o t he I NC (bilat erally f or upw ard burst
neurons), w hich provides t he st ep of innervat ion f or vert ical and t orsional
saccades (verti cal neural i ntegrator), and t o t he cell groups of t he PMT, w hich
project t o t he cerebellum. The I NC project s t o t he vert ical mot oneurons in t he
oculomot or and t rochlear subnuclei on t he cont ralat eral side of t he brainst em
t hrough t he PC. The I NC is import ant in holding t he eye in eccent ric gaze af t er a
vert ical saccade and coordinat ing eye–head movement s in roll. The nucl eus of
the PC also cont ains neurons t hat burst f or upw ard saccades t hat project
t hrough t he PC t o cont act t he riMLF and I NC. The nucleus of t he PC and t he
riMLF also project s t o t he m-group neurons (locat ed adjacent , medially, and
caudal t o t he riMLF), w hich relay signals t o t he cent ral caudal levat or subnucleus
of t he oculomot or nerve and t he elevat or subnuclei of t he eye elevat ors (SR and
I O ). The m-group of neurons coordinat es vert ical eye and lid movement s.
Lesions of t he m-group neurons or t he PC may t heref ore cause dissociat ed lid–
eye movement s during vert ical saccades (e. g. , impaired lid saccades in t he
presence of preserved eye saccades).
O mni pause cel l s lie in t he nucleus raphe int erposit us, w hich is locat ed in t he
midline, at t he level of t he abducens nerve. O mnipause cells send inhibit ory
project ions t o EBNs in t he pons, I BNs in t he medulla, and t o t he riMLF;
omnipause cells discharge cont inually except immediat ely bef ore and during
saccades, w hen t hey pause. Theref ore, omnipause neurons inhibit all burst cells,
prevent ing saccades w hen such movement s are not desirable, as during visual
f ixat ion [615] . Lesions of omnipause cells likely have a slow ing eff ect on
saccades in all direct ions [392] .
The Neural Integrator

For eye movement s, a pulse (velocit y command) causes a phasic cont ract ion of
t he ext raocular muscles t hat overcomes t he viscous drag of t he orbit and moves
t he eye t o it s dest inat ion. O nce t his dest inat ion has been reached, a st ep
(posit ion command) holds t he eye st eady at it s new posit ion by resist ing t he
elast ic rest oring f orces of t he orbit . Theref ore, ocular mot or neurons carry
inf ormat ion about bot h eye posit ion and eye velocit y. A mat hemat ical int egrat ion
is necessary t o convert velocit y-coded inf ormat ion t o posit ion-coded inf ormat ion
and t he st ruct ures responsible are called t he neural i ntegrator. For conjugat e,
horizont al eye movement s, t he neural int egrat or responsible f or gaze holding
resides in t he nucl eus proposi tus hypogl ossi (NPH) and t he adjacent MVN. The
NPH/ MVN have reciprocal connect ions w it h t he vest ibulocerebellum, especially
t he f locculus and paraf locculus t hat st abilize t he neural int egrat or, w hich is
inherent ly “leaky. ” The neural int egrat or f or vert ical conjugat e eye movement s
resides in t he INC.
G aze holding is t est ed by not ing t he pat ient 's abilit y t o hold t he eyes in an
eccent ric posit ion in t he orbit [480] . When t he neural int egrat or is impaired
(“leaky”), t he eyes w ill drif t back t ow ard primary posit ion at an exponent ially
decreasing rat e. This necessit at es a correct ive saccade result ing in gaze-evoked
nyst agmus. A unilat eral lesion of t he NPH/ MVN acut ely result s in part ial loss of
bot h ipsilat eral and cont ralat eral horizont al gaze holding. Bilat eral lesions abolish
neural int egrat ion f or all conjugat e horizont al eye movement s—horizont al
saccades are normal but t he eyes cannot be held in t he new posit ion.
O pt okinet ic and smoot h pursuit movement s are similarly aff ect ed. Bilat eral
lesions of t he I NC result in a part ial f ailure of vert ical gaze holding, w hile
vest ibulocerebellar damage makes t he neural int egrat or def icient . Bilat eral
blindness may also cause an inabilit y t o hold t he gaze st eady because t he neural
int egrat or depends on ret inal input s f or it s calibrat ion.
Collicular system
The SC cont ains neurons t hat discharge in relat ion t o saccadic eye movement s
and act s complement arily w it h t he FEF in t riggering saccades. I t has a dorsally
placed sensory port ion and a vent rally locat ed mot or port ion. The mot or port ion
receives it s excit at ory input f rom t he inf erior pariet al lobule (w hich receives
occipit al f ibers), f rom t he pariet al eye f ields–Pariet al Eye Fields (PEF) or lat eral
int rapariet al–Lat eral I nt rapariet al area (LI P), and f rom t he FEF direct ly. O t her
cort ical aff erent s originat e in t he pref ront al and supplement ary mot or cort ex.
The SC plays an import ant role in t he t riggering and inhibit ion of ref lexive visually
guided saccades. More caudally locat ed SC neurons project t o burst neurons in
t he cont ralat eral PPRF and t he ipsilat eral riMLF. The SC t ends t o deviat e t he
eyes t o t he cont ralat eral side, part icularly w hen a novel st imulus appears in t he
visual f ield. The SC programs visually guided saccades by encoding mot or error
signals and probably init iat es cont ralat erally direct ed spont aneous saccades and
quick phases of nyst agmus.
The pari etocol l i cul ar pathway is concerned w it h reorient ing t he gaze t o novel
visual st imuli and, in part icular, w it h shif t ing visual at t ent ion t o
t he locat ion of new t arget s appearing in ext rapersonal space. The superior part
of t he angular gyrus (Brodmann's area 39) in t he PPC is t he main area
f acilit at ing t he t riggering of ref lexive visually guided saccades [615] . Because
ref lexive visually guided saccade lat encies are increased bilat erally w it h right
PPC lesions, w hereas lef t post erior pariet al lesions increase lat ency only f or
saccades made cont ralat erally, t he right pariet al region could be dominant f or
ref lexive visually guided saccade cont rol [615] .
The FEF-col l i cul ar pathway is concerned w it h self -generat ed changes in gaze
relat ed t o remembered, ant icipat ed, or learned behavior (volunt ary saccades)
[ 480] . The FEF also act s on t he SC, indirect ly t hrough t he basal ganglia, in t he
process of maint aining and releasing f ixat ion. The supplement ary eye f ields–
Supplement ary Eye Fields (SEFs) are locat ed in t he post eromedial port ion of t he
f ront al lobe and have a role in planning saccades t o visual and nonvisual cues as
part of complex or learned behavior. This area plays a role in t he cont rol of
sequenti al eye movements (just as it plays a role in programming sequent ial limb
movement s), and lesions here, especially in t he dominant hemisphere, cause a
specif ic def icit in generat ing a sequence of t w o or t hree memory-guided
saccades [276, 279] . The dorsolat eral pref ront al cort ex–Dorsolat eral Pref ront al
Cort ex (DLPFC) (Brodmann's area 46) is involved in saccades t o remembered
locat ion of t arget s. Lesions of t he dorsolat eral pref ront al region t heref ore result
in def icit s in making saccades t o remembered t arget s. Lesions here also cause
an inabilit y t o suppress ref lex saccades t ow ard a visual t arget w hen a pat ient is
inst ruct ed t o make a saccade in a direct ion opposit e t o t he t arget (anti saccade
t asks) [614] . Theref ore, t he DLPFC is t he main area in t he cerebral hemisphere
inhibit ing ref lexive visually guided saccades [615] . Medial f ront al lobe lesions
also aff ect t he abilit y t o maint ain cent ral gaze f ixat ion [605] .
Part ial lesions of t he st riat e cort ex, w hich impair vision severely, may
nonet heless leave unaff ect ed t he abilit y t o produce saccades t o novel st imuli in a
port ion of t he visual f ield t hat is blind (“bl i nd si ght”) [171] . This phenomenon may
be mediat ed by t he SC, perhaps using ext rast riat al pat hw ays.
The SC also plays an import ant role in t he t riggering and inhibit ion of ref lexive
visually guided saccades [619] . Neurons at t he rost ral pole of t he mot or area of
t he SC appear t o play an import ant role in maint aining st eady f ixat ion and t hey
project t o omnipause neurons. These f ixat ion neurons suppress saccades and
also may be involved in disengagement f rom f ixat ion.
Higher Level Control of the Saccades

Three diff erent cort ical areas are capable of tri ggeri ng saccades [616, 792] .
1. Frontal Eye Fi el d (FEF). The FEF is locat ed around t he lat eral part of t he
precent ral sulcus, involving bot h t he post erior ext remit y of t he middle f ront al
gyrus and t he adjacent precent ral sulcus and gyrus, just ant eriorly t o t he
mot or cort ex. I t includes Brodmann's areas 6 and 4 (not 8). I t project s f ibers
t o t he SC and also direct ly t o t he premot or ret icular f ormat ions of brainst em,
and receives mult iple cort ical aff erent t ract s, especially f rom t he PEF, SEF,
and pref ront al cort ex (PFC or Brodmann's area 46). From t he FEF t he
impulses proceed caudally in a pat hw ay (t he vent ral pedunculot egment al
pat hw ay) t hat runs in t he ant erior limb of t he I C and medial port ion of t he
cerebral peduncle, decussat es at t he pont omesencephalic junct ion, and ends
in t he NRTP, w hich, in t urn, project s t o t he cerebellum. O t her cort icof ugal
pat hw ays include t he t ranst halamic pat hw ay, w hich project s t o t he ipsilat eral
SC and possibly t he riMLF, and a project ion t hrough t he ant erior limb of t he
I C t o t he caudat e, w hich, in t urn project s t hrough t he pars ret iculat a of t he
subst ant ia nigra, t o t he SC. The PPRF and midline raphe nucleus (omnipause
neurons) also receive FEF project ions.
Bilat eral st imulat ion of t he homologous point s of bot h FEFs is required t o
produce vert ical movement s. Some impulses reach t he caudal PPRF and
t hrough a para-MLF pat hw ay are conveyed t o t he mesencephalic ret icular
f ormat ion (bilat eral MLF lesions do not impair t he abilit y t o generat e vert ical
saccades). O t hers direct ly reach t he midbrain and caudal diencephalon
t hrough t he int ermediat e pref ront al oculomot or bundle.
The FEF cont rols t he f ollow ing:
A. Disengagement f rom f ixat ion is perhaps t hrough it s f ixat ion cells
project ing bot h t o t he brainst em ret icular f ormat ion and t o t he SC, in
w hich ot her f ixat ion cells exist .
B. Triggering of int ent ional ret inot opic saccades (int ent ionally visually
guided saccades, memory-guided saccades w it h visual input , predict ive
saccades, and correct ant isaccades). That is, t he FEF t riggers
int ent ional saccades t o visible t arget s, t o remembered t arget locat ions,
or t o t he locat ion w here it is predict ed t hat t he t arget w ill reappear (i. e. ,
saccades concerned w it h int ent ional explorat ion of t he visual

environment ).
C. The amplit ude of all (i. e. , ref lexive and int ent ional) cont ralat eral
ret inot opic saccades.
The main role of t he FEF is t o explore t he visual environment w it h
int ent ional saccades, f or w hich t he simple ret inoscopic f ramew ork is
suff icient t o calculat e saccade amplit ude.
2. Pari etal Eye Fi el d (PEF). The PEF is locat ed in t he region of int rapariet al
sulcus, t hat is, in t he superior part of t he angular gyrus and supramarginal
gyrus (Brodmann's areas 39 and 40). I t project s t o t he FEF and t he SC, but
not direct ly t o t he brainst em ret icular f ormat ion.
The PEF cont rols t he f ollow ing:
A. Perhaps disengagement f rom f ixat ion (upst ream f rom t he FEF), probably
by direct project ions t o t he SC.
B. Triggering of saccades made ref l exi vel y on t he sudden appearance of
visual t arget s (i. e. , saccades concerned w it h ref lexive explorat ion of t he
visual environment ).
The PEF is more involved in t he ref lexive explorat ion of t he visual
environment (t riggering ref lexive visually guided saccades), w hile t he
FEF is more involved in t he int ent ional explorat ion of t his environment
(int ent ional visually guided saccades).
Visual at t ent ion is mainly cont rolled by t he superi or pari etal l obul e
adjacent t o t he PEF. Bilat eral lesions aff ect ing t he PPC, including t he
PEF, or bot h t his cort ex and t he FEF, result in Balint 's syndrome (see
Chapt er 20) and acquired ocular mot or apraxia, respect ively, w it h severe
dist urbances of visually guided saccades in bot h cases.
3. Suppl ementary Eye Fi el d (SEF). The SEF lies in t he post eromedial part of
t he superior f ront al gyrus in t he supplement ary mot or area–Supplement ary
Mot or Area (SMA). I t receives mult iple cort ical aff erent t ract s, part icularly
f rom PFC and t he post erior part of t he cerebral hemisphere. The SEF
project s t o t he FEF, and, liket he FEF, t o t he SC and t o t he premot or ret icular
f ormat ions.
The SEF cont rols t he f ollow ing:
A. Triggering and amplit ude of memory-guided saccades w it h vest ibular
input (i. e. , using spat iot opic inf ormat ion) and saccades using craniot opic
inf ormat ion (i. e. , saccades using ext raret inal signals). SEF also appears
t o cont rol spont aneous saccades.
B. Triggering sequences of saccades and in cont rolling saccades made
during head or body movement (i. e. , saccades concerned w it h compl ex
motor programmi ng).
The main role of t he SEF could be t o prepare mot or programs, eit her combining
several int ent ional saccades or coordinat ing int ent ional saccades w it h ot her body
movement s, w hich require t he use of craniot ropic or spat iot opic coordinat es f or
calculat ing saccade amplit ude. Like t he SMA f or sequences involving limbs, t he
SEF cont rols mot or programs made up of several saccades.
Three ot her areas cont ribut e t o t he preparat ion of cert ain t ypes of saccades:
1. The pref rontal cortex (PFC, Brodmann's area 46) plays a crucial role f or
planning saccades t o remembered t arget locat ions. The dorsolat eral PFC
receives aff erent s f rom t he PPC, and project s t o t he FEF, SEF, and SC.
Lesions of t he PFC, f or example, w it h PSP, result in an increased
percent age of unw ant ed ref lexive visually guided saccades (in ant isaccade
paradigms); t heref ore, t he PFC cont rols inhibit ion of saccades, probably
t hrough t he SC rat her t han t he FEF.
2. The PPC is involved in visuospat ial int egrat ion, and project s t o t he PEF and
PFC. I t is likely near t he inf erior pariet al lobule adjacent t o t he PEF. The
inf erior pariet al lobule is involved in t he visuospat ial int egrat ion used f or
calculat ing saccade amplit ude; t he PPC direct s visual at t ent ion in
ext rapersonal space. As ref lexive visually guided saccade lat encies are
increased bilat erally w it h right PPC lesions, w hile lef t post erior pariet al
lesions increase lat ency only f or saccades made cont ralat erally, t he right
pariet al region could be dominant f or ref lexive visually guided saccade
cont rol.
3. The hi ppocampus (medi al temporal l obe) appears t o cont rol t he t emporal
w orking memory required f or memorizat ion of t he chronologic order of
sequences of saccades.
4. Experiment al and clinical st udies suggest t hat t he DLPFC and t he SC are
crucial f or t he cancellat ion of ref lexive eye movement s t ow ard dist ract ing
st imuli. How ever, t he cont ribut ion of subcort ical st ruct ures remains unknow n.
The basal ganglia provide serial t onic inhibit ory connect ions bet w een t he
DLPFC and t he SC, and could t heref ore be involved in prevent ing t he
t riggering of unnecessary saccades. The DLPFC could also exert it s
inhibit ory eff ect on t he SC t hrough direct pref ront o-t ect al pat hw ays t hat
t ravel in t he I C. Since t halamic dysf unct ion may be responsible f or reduced
DLPFC act ivat ion, it may be hypot hesized t hat t he t halamus could also
part icipat e in saccadic inhibit ion. A st udy by Condy et al. , how ever,
suggest ed t hat neit her t he basal ganglia nor t he t halamus plays
a major role in ref lexive saccade suppression, but support ed t he hypot hesis
of a direct DLPFC inhibit ory cont rol of saccade t riggering on t he SC [164] .
Thal ami c structures also t ake part in saccadic eye movement s. The laminar or
int ralaminar nuclei of t he t halamus receive input s f rom t he FEF, SEF, and inf erior
pariet al lobule as w ell as f rom t he SC, basal ganglia, and cerebellum. This
region of t he t halamus may help cont rol saccadic accuracy and t he abilit y t o
mat ch eye posit ion t o t arget posit ion. The pulvinar may have a role in t he
maint enance and shif t of visual at t ent ion (probably in coordinat ion w it h t he
pariet al cort ex) [480] , and pulvinar lesions may cause a paucit y of spont aneous
saccades int o t he cont ralat eral f ield and increased saccadic lat encies f or all
saccades, especially t hose direct ed cont ralat erally.
The Basal Ganglia

I nhibit ory neurons t o t he SC are locat ed in t he subst ant ia nigra (pars ret iculat a).
These neurons act in a t onic f ashion, t heir act ivit y ceasing immediat ely prior t o
visually guided and memory-guided saccades. The subst ant ia nigra pars
ret iculat a in t urn receives inhibit ory (and possibly excit at ory) connect ions f rom
t he caudat e nucleus t hat , in t urn, receives aff erent s f rom t he f ront al lobe. For
ref lexive visually guided saccades, t he f ront al cort ex is mainly inhibit ory.
Theref ore, some pat ient s w it h f ront al lesions aff ect ing t he superior part of t he
pref ront al cort ex may be unable t o inhibit unw ant ed saccades. The basal ganglia
syst em f or saccadic cont rol t heref ore has t w o serial inhibit ory links: caudo-nigral
inhibit ion (phasic, G ABA mediat ed) and nigro-collicular inhibit ion (t onic, G ABA
mediat ed). Front al pat hw ays excit e caudat e neurons t hat block t he inhibit ory
aff ect of t he subst ant ia nigra on t he SC and, t heref ore, act ivat e a saccade. The
basal ganglia gat e, select ively, ref lexive and volunt ary saccades generat ed by
t he SC. The syst em f acilit at es t he init iat ion of more volunt ary, self -generat ed
saccades made in t he cont ext of learned behavior (e. g. , memory-guided or
predict ive saccades) and aids in st eady f ixat ion by prevent ing unw ant ed,
ref lexive saccade t o disrupt ive st imuli [480] . Caudat e lesions may cause loss of
phasic SC disinhibit ion result ing in impaired saccade init iat ion, w hile lesions of
t he subst ant ia nigra allow t he SC t o be released f rom t onic inhibit ion result ing in
ext raneous saccades (excessive and inappropriat e saccades). Caudat e lesions
may also decrease t he accuracy of memory-guided saccades [812] .
In summary, t he inf luence of t he f ront al and pariet al cort ex on t he cont rol of
saccades appears t o be t hrough t w o parallel descending pat hw ays. O ne
pat hw ay is t hrough t he FEF t o t he SC (direct ly and indirect ly t hrough t he basal
ganglia). This pat hw ay appears t o be concerned w it h self -generat ed changes in
gaze relat ed t o ant icipat ed, learned, or remembered behavior. The ot her
pat hw ay is direct ly f rom t he PPC t o t he SC and is concerned w it h reorient ing
gaze t o novel visual st imuli and part icularly w it h shif t ing visual at t ent ion t o
locat ion of new t arget s appearing in ext rapersonal space. There is likely a
hemisphere asymmet ry f or eye gaze mechanisms. St udies suggest t hat t he right
cerebral hemisphere is dominant w it h respect t o at t ent ional/ int ent ional
mechanisms direct ed at ext ernal space [520] .
Lesions of t he FEF impair nonvisually guided, int ent ional saccades but not
visually guided, int ent ional saccades, w hereas pariet al-occipit al lesions impair
visually guided, int ent ional saccades but not nonvisually guided, int ent ional
saccades. FEF lesions cause a t ransient neglect (decreased saccade f requency
and size) cont ralat erally and a def ect in generat ing volunt ary saccades,
especially ant icipat ory saccades and saccades t o remembered t arget s.
Unilat eral pariet al lesions cause unilat eral or bilat eral increased saccade
lat encies, hypomet ric cont ralat eral saccades, and saccadic slow ing. Bilat eral
pariet al lesions result in an acquired f orm of ocular mot or apraxia (see
subsequent t ext ) w it h a def icit in generat ing visually guided saccades great er
t han t he def icit f or volunt ary saccades [612] . Bilat eral f ront opariet al lesions
cause a marked def icit of bot h volunt ary and visually guided saccades [611] .
Combined lesions of t he FEF and t he ipsilat eral SC cause severe and permanent
impairment of saccades t o t he cont ralat eral side.
Cerebellum
The cerebellum plays a role in t he cont rol of saccadic eye movement s. A major
project ion f rom t he cort ical eye f ields is t o t he cerebellum, t hrough t he pont ine
nuclei. The NRTP lies vent ral t o t he rost ral PPRF and receives input s f rom t he
FEF and SEF. The NRPT project s f ibers t o t he dorsal vermis and caudal f ast igial
nucleus of t he cerebellum and t o t he PPRF.
The dorsal vermis (lobules VI and VI I ), and underlying f ast igial nucleus, modulat e
t he amplit ude of t he saccadic pulses. The caudal part of t he f ast igial nucleus,
t he f ast igial oculomot or region–Fast igial O culomot or Region (FO R), also
receives a copy of t he saccadic commands, w hich are relayed t hrough t he NRTP
f rom t he FEF and SC. The f ast igial out f low passes
cont ralat erally t hrough t he uncinat e f asciculus in t he dorsolat eral brachium

conjunct ivum t o reach t he PPRF and riMLF neurons. The f ast igial nucleus might
inf luence saccades by providing early drive t o burst neurons during cont ralat eral
saccades and a lat e brake during ipsilat eral ones.
St imulat ion of t he dorsal vermis evokes conjugat e saccades ipsilat erally; t his
eff ect represent s st imulat ion of Purkinje cells, w hich inhibit t he underlying
f ast igial nucleus. St imulat ion of t he f ast igial nucleus elicit s cont ralat eral
saccades. Theref ore, lesions of t he dorsal vermis or brachium conjunct ivum
produce ipsilat eral saccade hypomet ria and cont ralat eral saccade hypermet ria,
w hile lesions of t he f ast igial nucleus produce ipsilat eral saccade hypermet ria
(i psi pul si on) and hypomet ria of cont ralat eral saccades [278, 480] . The f indings
relat ed t o unilat eral f ast igial nucleus lesions are similar t o t he lat eralpulsion
not ed w it h Wallenberg lat eral medullary syndrome. Bilat eral vermis lesions lead
t o hypomet ric saccades, and bilat eral FO R lesions t o hypermet ric saccades
[ 131] . I nf arct ion in t he t errit ory of t he superior cerebellar art ery, involving t he
superior cerebellar peduncle, causes contrapul si on of saccades: horizont al
saccades aw ay f rom t he lesion are hypermet ric, ipsilat eral saccades are
hypomet ric, and at t empt ed vert ical saccades are direct ed obliquely aw ay f rom
t he side of t he lesion [640, 739] . This saccadic lat eropulsion is t hought t o be due
t o a lesion of t he eff erent pat hw ays f rom t he caudal f ast igial nucleus [131, 739] .
O cular cont rapulsion in pat ient s w it h mult iple sclerosis likely result s f rom a
lesion in t he region of t he superior cerebellar peduncle, involving t he uncinat e
f asciculus [251] .
Vermian cerebellar lesions also impair an int erest ing adapt ive capabilit y of t he
saccadic syst em (i. e. , repair of ocular dysmet ria). Normally, if lat eral rect us
w eakness develops, t he involved eye makes hypomet ric saccades. I f t he sound
eye is t hen pat ched, t he saccadic syst em is soon readjust ed, so t hat t he
abduct ing saccades produced by t he aff ect ed eye f all on t arget (are
ort homet ric), w hereas t he adduct ing saccades of t he f ellow eye become
hypermet ric.
The f locculus (and perhaps t he paraf locculus) appears t o be responsible f or
mat ching t he saccadic st ep t o t he pulse [480] . Floccular lesions cause
post saccadic drif t , or inabilit y t o maint ain t he globe in t he new ly acquired
eccent ric posit ion af t er a saccade (t he eye drif t s cent ripet ally causing gaze-
evoked nyst agmus), but do not cause saccadic pulse dysmet ria. The cerebellum
has been implicat ed in conjugat e ocular mot or cont rol, including st eady gaze
holding. Pat ient s w it h cerebellar disease may have dist urbances of ocular
alignment , including esophoria during monocular view ing or an ET during
binocular view ing, implying an increase in convergence t one. Many pat ient s may
have a vert ical misalignment t hat varies w it h horizont al eye posit ion (alt ernat ing
skew deviat ion) [813] .
I t is evident f rom t he previous discussions t hat t he cerebellum plays a crucial
role in t he cont rol of vest ibulo-ocular, pursuit , and saccadic eye movement s
[ 480] . Lesions of t he dorsal vermis (lobules I V-VI ) and f ast igial nucleus cause
enduring saccadic dysmet ria, mild def icit s of smoot h pursuit , and, occasionally,
macrosaccadic oscillat ions. For example, lesions aff ect ing t he post erior vermis
cause bilat eral saccadic hypomet ria and a decrease in ipsilat eral smoot h pursuit
gain [799] . Lesions of t he f locculus and paraf locculus (vest ibulocerebellum)
impair ipsilat eral smoot h pursuit and gaze holding, cause post saccadic drif t ,
impair t he vest ibulo-ocular ref lex, and may be associat ed w it h gaze-evoked,
rebound, or dow nbeat nyst agmus (DBN). Finally, nodular lesions prolong t he
vest ibular responses and result in periodic alt ernat ing nyst agmus–Periodic
Alt ernat ing Nyst agmus (PAN) [480] . Nyst agmus is discussed in t he subsequent
t ext .
Abnormal Saccades
Saccadic eye movement s are t est ed at t he bedside by inst ruct ing t he pat ient t o
f ixat e alt ernat ely upon t w o t arget s (e. g. , t he t ip of t he examiner's f inger and t he
examiner's nose) not ing saccadic lat ency, t raject ory, accuracy, and conjugacy
[ 480] . The quick phases induced by an opt okinet ic drum or t ape also assess
saccadic eye movement s. Lesions in t he st ruct ures t hat mediat e t he product ion
of saccades may result in saccades t hat are inappropriat e, inaccurat e
(hypermet ric or hypomet ric), t oo slow or t oo f ast , or saccades t hat are poorly
init iat ed.
1. I nappropriat e saccades, or saccadi c i ntrusi ons, int erf ere w it h macular

f ixat ion of an object of int erest . There are several t ypes of inappropriat e
saccades:
A. Square-wave jerks t ake t he eyes off t he t arget and are f ollow ed af t er
about 200 milliseconds by a correct ive saccade. They may appear
normally in t he young and t he elderly, but w hen larger t han 1 or 2
degrees t hey are pat hologic, result ing f rom a variet y of disorders
especially cerebellar disease and PSP. Here t hey may be due t o
impairment of t he normal f ixat ion mechanism, w hich exert s it s eff ect
t hrough t he rost ral SC. I n cerebellar disease t here may be damage t o
t he f ast igial nucleus, w hich project s
t o t he rost ral SC, and t he SC is of t en involved pat hologically in PSP.

Square-w ave jerks have also been described w it h Alzheimer's disease,
Hunt ingt on's disease, Parkinson's disease, Wernicke-Korsakoff 's
syndrome, amyot rophic lat eral sclerosis, Friedreich's at axia, acquired
immunodef iciency syndrome (AI DS)–dement ia complex, G erst mann-
St raussler-Scheinker disease, adult -onset Alexander's disease,
carbohydrat e-def icient glycoprot ein syndrome t ype 1a, and schizophrenia
[ 249, 643, 733, 853] . They may also occur w it h lit hium or t obacco use.
An increased f requency of square-w ave jerks may be not ed af t er
unilat eral pallidot omy f or Parkinson's disease [38] . Very f requent square-
w ave jerks (called square-wave osci l l ati ons) may occur w it h cerebellar
disease, PSP, and cerebral hemispheral disease.
B. Macrosquare wave jerks are similar t o square-w ave jerks but are of
larger amplit ude (20 t o 40 degrees). They are occasionally present in t he
vert ical plane and have been not ed in mult iple sclerosis, cerebellar
hemorrhage, olivopont ocerebellar at rophy, mult iple syst ems at rophy, and
w it h Arnold-Chiari malf ormat ion.
C. O cul ar f l utter is a burst of t o-and-f ro horizont al saccades w it hout an
int ersaccadic int erval. O ccasionally, ot herw ise normal individuals show
int ermit t ent , 15 t o 30 Hz f requency, low amplit ude (0. 1 t o 0. 5 degrees),
horizont al oscillat ions (seen only w it h t he opht halmoscope) t ermed
mi crosaccadi c f l utter [ 30] . Pat ient s w it h microsaccadic f lut t er of t en
complain of “shimmering, ” “jiggling, ” “w avy, ” or “laser beams” w it h
paroxysms of visual dist urbances last ing seconds t o hours. Dizziness or
dysequilibrium of t en accompanies t he visual sympt oms. Most pat ient s
are ot herw ise normal, alt hough one pat ient had mult iple sclerosis [30] .
D. O psocl onus (saccadomani a) is similar t o ocular f lut t er, except t hat in
opsoclonus t here are conjugat e, involunt ary, large amplit ude saccades in
all direct ions. Like ocular f lut t er, opsoclonus indicat es brainst em,
especially mesencephalic, or cerebellar disease. O psoclonus persist s
during eye closure and during sleep and is t hought t o be due t o
dysf unct ion of omnipause neurons t hat normally exert t onic inhibit ion on
burst neurons [353, 648] . This disorder has been described in pat ient s
w it h purely pont ine lesions [334] . O psoclonus is of t en part of a syndrome
w it h myoclonus of t he t runk and limbs and cerebellar dysf unct ion and
may be seen as a paraneoplast ic eff ect w it h neuroblast oma or ot her
t umors (especially small-cell lung cancer and breast cancer) [74, 86,
648] . These movement s have also been observed in pat ient s w it h viral
encephalit is and hepat it is, meningit is, t rauma, int racranial (especially
dorsal mesencephalic) t umor, hydrocephalus, int racranial hypert ension
f rom venous t hrombosis, t halamic or pont ine hemorrhage, mult iple
sclerosis, hyperosmolar nonket ot ic coma, primary Sjögren's syndrome,
sarcoidosis, AI DS, or t oxic encephalopat hy induced by lit hium, phenyt oin
plus diazepam, cocaine, phenelzine plus imipramine, st rychnine, t oluene,
organophosphat es, chlordecone, t hallium, or amit ript yline [205, 465] .
O psoclonus evident only during eye closure has been described w it h
heredit ary cerebellar at axia [335] . O cular f lut t er has been described in a
pat ient w it h mult iple sclerosis w it h a lesion aff ect ing t he PPRF,
suggest ing t hat at least in some cases, ocular f lut t er may be due t o
lesions involving t he PPRF [694] . Vol untary nystagmus (more correct ly
t ermed psychogeni c f l utter [ 480] ) occurs in normal subject s and consist s
of burst s of high-f requency horizont al oscillat ions composed of back-t o-
back saccades. The movement s may be vert ical or t orsional as w ell. This
movement w ill complet ely disappear if pat ient s are f orced t o keep t heir
eyes open, since it requires t remendous volit ional eff ort and cannot be
sust ained f or prolonged periods of t ime [128] . Volunt ary nyst agmus is
of t en accompanied by a “f ixed look” required t o produce t he sympt oms,
eyelid f lut t er, and convergence spasm [683] .
Foroozan et al. described t he clinical present at ion of a disorder t ermed
i di opathi c mi crosaccadi c opsocl onus [ 245] . A 67-year-old man w it h
int ermit t ent blurred vision and oscillopsia, w hich persist ed w it h monocular
occlusion, over a 5-year period w as f ound t o have high f requency, small
amplit ude back-t o-back mult ivect orial saccadic movement s, w hich w ere
visible w it h slit lamp biomicroscopy and direct opht halmoscopy. Video-
oculography show ed a 20 Hz, 0. 2 t o 1 degree pat t ern of horizont al, vert ical,
and t orsional microsaccades. This microsaccadic disorder has persist ed f or
5 years w it h no et iology. Microsaccadic opsoclonus is
an idiopat hic disorder t hat present s w it h oscillopsia and int ermit t ent blurred
vision.
2. Impai red i ni ti ati on of saccades, w it h abnormally increased lat encies, can be
t he consequence of disease anyw here in t he pat hw ays mediat ing saccade
product ion. Saccades t ow ard t he side cont ralat eral t o t he lesion are delayed
w it h f ront al or collicular damage. Pont ine lesions impair saccades t o t he side
of t he injury. I n all t hese cases, t he saccades t end t o be hypomet ric as w ell.
Saccadic lat encies may act ually be decreased in PSP or w it h f ocal
hemispheral lesions [609, 617] . A st riking disorder of saccade init iat ion is
ocul ar apraxi a, charact erized by an impaired abilit y t o generat e saccades on
command, alt hough ref lexly induced saccades (bot h t o visual t arget s during
spont aneous visual search and t o vest ibular and opt okinet ic st imulat ion) and
random saccades are normal. This abnormalit y is part of Balint 's syndrome
(see Chapt er 20). O cular apraxia may be congenit al [328, 608, 623, 706] , in
w hich t he abnormalit y is almost alw ays rest rict ed t o t he horizont al plane and
is associat ed w it h charact erist ic t hrust ing horizont al head movement s
somet imes w it h prominent blinking (rare vert ical cases since birt h have been
described [215] ). When acquired lat er in lif e, ocular apraxia usually occurs in
t he vert ical as w ell as t he horizont al plane and usually indicat es bilat eral
hemispheric disease, especially f ront al or f ront opariet al [186, 215, 280, 611,
612] . I mpaired scanning of a complex pict ure, leading t o bizarre
int erpret at ions of visual scenes, is also charact erist ic of t he pat ient s w it h
bilat eral f ront al disease. O cular mot or apraxia in bot h t he horizont al and
vert ical planes associat ed w it h at axia and choreoat het osis may occur in
heredit ary spinocerebellar degenerat ions (e. g. , recessive at axia w it h ocular
apraxia) [11, 58, 462] , w it h Niemann-Pick variant s, or as part of t he disorder
know n as at axia-t elangiect asia. Purely vert ical saccadic apraxia (random but
not volunt ary saccades int act ) associat ed w it h memory impairment has been
described w it h bilat eral medial t halamic lesions [533] . Saccadic
abnormalit ies are common w it h parkinsonian syndromes and w it h progressive
at axic syndromes [549, 817] .
3. I naccurat e or dysmetri c saccades usually point t o brainst em or cerebellar
disease [101] . Pat ient s w it h cerebellar disease of t en have signif icant ly larger
saccadic amplit udes (hypermet ria) at least in one direct ion [101] . Lesions of
t he superior vermis or brachium conjunct ivum cause hypermet ria aw ay f rom
t he side of t he lesion w hile lesions of t he f ast igial nucleus produce ipsilat eral
saccade hypermet ria. Wallenberg syndrome may be associat ed w it h
ipsipulsion of saccades w hile superior cerebellar peduncle lesions, rost ral
cerebellar lesions, caudal lesions of t he medulla, and medial medullary
lesions cause cont rapulsion of saccades [431, 432, 640, 779] . Ext reme
saccadic hypermet ria produces macrosaccadi c osci l l ati ons (a series of
hypermet ric saccades) about t he t arget . Macrosaccadic oscillat ions are
diff erent f rom square-w ave jerks and consist of eye oscillat ions around t he
f ixat ion angle w it h int ersaccadic int ervals approximat ely 200 milliseconds
[ 480] . They are usually conjugat e, horizont al, and symmet ric in bot h
direct ions of gaze, but may occur in t orsional or vert ical planes.
Macrosaccadic oscillat ions are encount ered in cerebellar disease t hat
involves t he f ast igial nucleus and w it h pont ine lesions t hat involve omnipause
neurons [36] . For example, a recessive disorder, designat ed spi nocerebel l ar
ataxi a wi th saccadi c i ntrusi ons, has been described in w hich aff ect ed
pat ient s show ed overshoot ing horizont al saccades, macrosaccadic
oscillat ions, and increased velocit y of larger saccades, w hile ot her eye
movement s w ere normal [749] . Macrosaccadic oscillat ions may be induced
by edrophonium (Tensilon) in pat ient s w it h prof ound opht halmoplegia f rom
myast henia gravis [442] . Also, pat ient s w it h a hemispheric lesion result ing in
a homonymous f ield def ect may make hypermet ric saccades t ow ard t he side
of t he f ield def ect in order t o visualize object s placed in t hat direct ion.
Pat ient s w it h Lambert -Eat on myast henic syndrome may have hypomet ric,
closely spaced saccades; t he charact erist ic f acilit at ion of muscle pow er in
t his syndrome can somet imes be demonst rat ed during repet it ive saccades as
hypomet ria gives w ay t o hypermet ria [480] .
I n Al zhei mer's di sease, saccades are of t en abnormal [240] . I n advanced
cases, t here may be i mpersi stence of gaze, manif est ed by large amplit ude
saccadic int rusions aw ay f rom t he int ended posit ion of gaze. When inst ruct ed
t o make saccades aw ay f rom a t arget (ant isaccadic t ask), some pat ient s
make ref lex saccades t ow ard t he t arget (vi sual grasp ref l ex) [240] .
Abnormalit ies of ant isaccade t asks also occur w it h PSP, AI DS, and G illes de
la Touret t e syndrome [614, 741] . G aze di stracti bi l i ty (inabilit y t o f ix t he eyes
on a st at ionary or moving t arget f or more t han a f ew seconds w it hout being
dist ract ed by alt ernat ive peripheral t arget s) may be seen in Alzheimer's
disease and also
w it h discret e f ront al lobe lesions, in Hunt ingt on's disease, in schizophrenia,

and in Wilson's disease [483] . Pat ient s w it h HIV i nf ecti on of t en demonst rat e
ocular mot or abnormalit ies, including impaired saccadic accuracy, impaired
saccadic lat ency, impaired f ixat ion st abilit y, and abnormalit y of ant isaccade
t asks [385, 523] . Pat ient s w it h attenti on def i ci t hyperacti vi ty
di sorder–Attenti on Def i ci t Hyperacti vi ty Di sorder ( ADHD) have impaired
perf ormance in ant isaccade t asks and impaired memory-guided saccades,
f indings consist ent w it h def icit s in response init iat ion [556] . Pat ient s w it h
l ate-onset Tay-Sachs di sease–Late-O nset Tay-Sachs Di sease ( LO TS), an
adult -onset , aut osomal recessive progressive variant of G M2 gangliosidosis,
show charact erist ic abnormalit ies of saccades but normal aff erent visual
syst ems [668] . Hypomet ria, t ransient decelerat ions, and premat ure
t erminat ion of saccades suggest disrupt ion of a “lat ch circuit ” t hat normally
inhibit s pont ine omnipause neurons, permit t ing burst neurons t o discharge
unt il t he eye movement is complet ed.
Pat ient s w it h Creutzf el dt-Jakob di sease may show a charact erist ic ocular
abnormalit y—geotropi c ocul ar devi ati on wi th skew and absence of saccades
[ 855] . When t he head is t urned t o one side, t he eyes very slow ly deviat e t o
t hat side, w hile t he abduct ing eye moves upw ard and t he adduct ing eye
moves dow nw ard. Spont aneous ocular movement s are very slow w it h no
saccadic component . They may also develop PAN (see subsequent t ext ) and
slow vert ical saccades (especially upw ard) suggest ing involvement of t he
cerebellar nodulus and uvula, and brainst em ret icular f ormat ion, respect ively
[ 297] . Anot her saccadic abnormalit y in Creut zf eldt -Jacob disease is periodic
alt ernat ing gaze deviat ion w it h t onic deviat ion of t he eyes and t he head t o
one side f or a period of t w o t o t w o-and-a-half minut es f ollow ed by slow
deviat ion over 10 t o 15 seconds t o t he opposit e side w here t he head and
eyes remain deviat ed f or a similar durat ion bef ore t he cycle repeat s.
Cent ripet al nyst agmus may also occur w it h Creut zf eldt -Jacob disease [341] .
4. Abnormal saccadi c vel oci ty may have various causes. Saccades t hat appear
t o be t oo f ast usually represent a normal-velocit y saccade st opped in
midf light . They are charact erist ically f ound in myast henia gravis, w hen
muscle f at igue (int rasaccadic f at igue) prevent s t he saccade f rom evolving t o
complet ion or slow s t he saccade in midf light so t hat t he eye creeps up t o it s
t arget . The saccade, rat her t han being t oo f ast , is act ually t oo small. This
f at igue may cause t he saccade t o st op in midf light w it h a drif t backw ard
result ing in a relat ively specif ic jelly-like bilat eral quiver movement ; t his
quiver consist s of an init ial small saccadic movement f ollow ed by a rapid
drif t backw ard. I n myast henia, large saccades may be hypomet ric and small
saccades may be hypermet ric. Edrophonium (Tensilon) inject ion may cause
saccades t o be hypermet ric, somet imes w it h cont inuous t o-and-f ro
movement s about t he t arget (macrosaccadic oscillat ions) [480] .
Slow saccades occur in t he direct ion of a paret ic ext raocular muscle or in t he

adduct ing eye w it h an ipsilat eral MLF lesion. I n t hese cases, t he range of mot ion
is limit ed (hypomet ric saccades). When t he range of mot ion is f ull, slow
saccades in t he horizont al plane usually result f rom bilat eral PPRF disease,
w hile slow ing in t he vert ical plane suggest s impairment in t he riMLF. Slow
horizont al saccades probably ref lect damage t o EBNs or omnipause neurons.
Slow saccades have been described w it h olivopont ocerebellar at rophy and ot her
spinocerebellar at axias (especially SCA 2 and SCA 7), Parkinson's disease,
Hunt ingt on's disease, Whipple's disease, Alzheimer's disease, amyot rophic
lat eral sclerosis, t et anus, paraneoplast ic syndromes, AI DS-associat ed dement ia,
Wilson's disease, at axia-t elangiect asia, PSP, and lipid st orage disorders.
Pat ient s w it h PSP have slow ing of vert ical (up and dow n) saccadic velocit y w hile
pat ient s w it h cort icobasal degenerat ion have preserved saccadic velocit y w it h
increased saccadic lat ency (i. e. , delayed init iat ion), especially ipsilat eral t o t he
apraxic side [477, 653] . Slow saccades and saccadic dysmet ria may occur w it h
chronic pet rol sniff ing and lead encephalopat hy [134] . Drow sy, inat t ent ive, or
sedat ed pat ient s (e. g. , ant iconvulsant s or benzodiazepines) may also have slow
saccades.
Convergence System
Convergence and divergence (disjunct ive) movement s of t he eyes bring about
binocular vision. Like convergence, divergence is not a purely passive process
but requires act ive cont ract ion of eye muscles. Bot h eye movement s aim at
placing a point of t he visual f ield in homologous point s of bot h ret inas, most
of t en t he maculae. Near object s elicit convergence, w hereas dist ant ones elicit
divergence of t he axes of bot h eyes. Vergence movement s are accompanied by
accommodat ion of t he lens t o prevent t he blur t hat result s f rom a poorly f ocused
image. An object approaching t he subject in t he sagit t al plane induces t he “near-
tri ad”
ref l ex composed of convergence, rounding of t he lens (accommodat ion), and

const rict ion of t he pupil (miosis). Vergence movement s are much slow er t han
saccades or pursuit , proceeding as long as one second. I n most nat ural
circumst ances, how ever, vergence movement s are used in combinat ion w it h
saccades or pursuit eye movement s.
The neuronal groups or pat hw ays involved in convergence remain poorly
underst ood [833] . St imulat ion of areas 19 or 22 of t he occipit al cort ex may
induce some of t he element s of t he near-t riad. Descending f ibers f rom cort ical
convergence areas probably decussat e in t he t halamot ect al area (perhaps in t he
paramedian t halamus [627, 833) and cont rol premot or vergence neurons.
Vergence premot or neurons, so-called near response cells, lie in t he midbrain
dorsal and dorsolat eral t o t he oculomot or nucleus and in t he medial NRTP [517] .
These near response cells can be divided f unct ionally int o convergence and
divergence neurons [517] .
Most nat ural shif t s of t he visual point of f ixat ion bet w een t arget s are locat ed at
diff erent dist ances and in diff erent direct ions. Such sudden or “st ep” ref ixat ions
require combined saccade–vergence movement s. The vergence component of
such movement s is speeded up by t he synchronous saccade and is somet imes
ref erred t o as “f ast ” vergence. “Slow ” vergence movement s (less t han 2
deg/ second) can be induced by moving a t arget smoot hly t ow ard t he pat ient 's
nose, as is commonly done during a clinical examinat ion. Neuronal st ruct ures f or
“f ast ” and “slow ” vergence might be anat omically separat ed in t he pons under
nat ural view ing condit ions. Lesions aff ect ing t he NRTP caused not only impaired
conjugat e smoot h pursuit eye movement s but also def icit s in vergence t o ramp
and sinusoidal t arget s (const ant peak vergence velocit y of 1. 5 deg/ second) but
not t o “st ep” t arget s [638] . Pont ine nuclei t heref ore appear t o be involved in t he
slow vergence cont rol [638] . “Fast ” vergence may be impaired by midbrain and
upper pont ine lesions [639] .
Convergence and divergence neurons project t o t he MR and lat eral rect us,
respect ively. The cerebellar f locculus also has neurons t hat discharge in relat ion
t o t he vergence angle. Vergence movement s involve f ine coordinat ion bet w een
t he abducens and t he oculomot or nuclei, but f or vergence t he link bet w een t hese
nuclei probably courses out side t he MLF because MLF lesions respect
convergence.
During convergence, t he pupillary sphinct er const rict s t he pupil as
parasympat het ic impulses f rom t he Edinger-West phal nucleus reach t he pupil by
w ay of t he t hird nerve and ciliary ganglion. Lesions aff ect ing t he midbrain, t hird
nerve, or ciliary ganglion may cause paresis of t he iris sphinct er. I n t hese cases,
t he light ref lex t ends t o be involved earlier and t o a great er ext ent t han in
convergence (light -near dissociat ion) because t he cont ingent of pupillomot or
f ibers mediat ing convergence out numbers t he ones mediat ing t he light ref lex.
Adie's t onic pupil, discussed in t he preceding t ext , exemplif ies t his diff erent ial
innervat ion.
Convergence i nsuf f i ci ency is common among t eenagers and college st udent s
(especially t hose w it h an increased visual w ork load) but may also be seen in t he
elderly, af t er mild head t rauma, and w it h acquired cerebral lesions (especially
t hose aff ect ing t he nondominant pariet al lobe) [480, 588] . Pat ient s w it h
convergence insuff iciency t ypically complain of eyest rain and ache. Af t er brief
periods of reading, t he let t ers w ill blur and run t oget her and of t en diplopia
occurs during near w ork. Typically, t he pat ient w ill close or cover one eye w hile
reading t o obt ain relief f rom visual f at igue. Pat ient s have an exodeviat ion great er
at near t han at dist ance but adduct ion is usually normal and t here is a remot e
near point of convergence [821] . Parkinson's disease and PSP may also be
associat ed w it h impaired or absent convergence.
Pat ient s w it h convergence paral ysi s, as opposed t o convergence insuff iciency,
of t en harbor a lesion of t he midbrain. Diplopia exist s only at near f ixat ion,
adduct ion is normal, and t he pat ient is unable t o converge. Preservat ion of
accommodat ion or pupillary miosis at near conf irms an organic et iology. O t her
signs of midbrain damage are usually present including impaired vert ical gaze,
upbeat or DBN, convergence-ret ract ion nyst agmus, and eyelid ret ract ion. Many
condit ions are associat ed w it h convergence paralysis, including Parkinson's
disease, PSP, dorsal midbrain t umors, midbrain hemorrhage or inf arct ion,
mult iple sclerosis, encephalit is, met abolic causes, t rauma, subdural hemat oma,
and drugs [630, 731] . Accommodat ion and convergence palsy has been
described in a pat ient w it h bilat eral rost ral SC lesions [587] . Because
descending f ibers f rom cort ical convergence areas probably decussat e in t he
t halamot ect al area, dissociat ed unilat eral convergence paralysis has been
described w it h t halamot ect al hemorrhage [492] , and bilat eral paramedian
t halamic inf arct ion can cause select ive loss of vergence cont rol and dissociat ion
of t he light -near ref lex [833] .
Convergence spasm (spasm of the near ref l ex) most of t en occurs on a
f unct ional basis [290, 821] . The spasm may be t riggered by asking t he pat ient t o
f ixat e an object held closely bef ore t he eyes;
af t er t he f ixat ion object has been removed, t he eyes w ill remain in a convergent
posit ion [821] . Q uick saccades back and f ort h in t he horizont al plane may also
induce t he spasm. Pat ient s may init ially be t hought t o have unilat eral or bilat eral
abducens nerve paresis (or myast henia gravis but t he observat ion of miosis
during t he spasm in a pat ient w it h apparent unilat eral or bilat eral limit at ion of
abduct ion and severe myopia (8 t o 10 diopt ers) indicat es t he correct diagnosis
[ 290] . This miosis generally resolves as soon as eit her eye is occluded.
I ncreased or sust ained convergence may also be seen w it h lesions of t he
diencephalic–mesencephalic junct ion. For example, a pseudo-sixt h nerve palsy
may occur f rom midbrain lesions (mi dbrai n pseudo-si xth nerve pal sy), perhaps
due t o an excess of convergence t one [522, 627] . I n a st udy of pat ient s w it h
pseudoabducens palsy and “t op of t he basilar” inf arct s, t he smallest inf arct s
producing an ipsilat eral pseudoabducens palsy w ere locat ed just rost ral t o t he
oculomot or nucleus, near t he midbrain–diencephalic junct ion [627] . Tw o pat ient s
w it h only cont ralat eral pseudoabducens palsy had subt halamic and t halamic
inf arct ion and f our pat ient s w it h bilat eral pseudoabducens palsy had larger
inf arct s involving t he midbrain. All pat ient s w it h pseudoabducens palsy had
upgaze palsy. The aut hors concluded t hat lesions near t he midbrain–diencephalic
junct ion are import ant f or t he development of pseudoabducens palsy and t hat
t his abnormalit y and convergence-ret ract ion nyst agmus are bot h manif est at ions
of abnormal vergence act ivit y. I nhibit ory descending pat hw ays f or convergence
may pass t hrough t he t halamus and decussat e in t he subt halamic region [627] .
Theref ore, acut e ET has been described w it h cont ralat eral t halamic inf arct ion in
t he t errit ory of t he mesencephalic art ery (acute thal ami c ET) [291] . Tonic
act ivat ion of t he MR muscle in t hese cases could result f rom damage t o direct
inhibit ory project ions f rom t he t halamus or impairment s of input s t o midbrain
neurons involved in vergence cont rol. Acut e t halamic hemorrhage may cause
bilat eral asymmet ric ET w it h t he cont ralat eral eye more aff ect ed t han t he
ipsilat eral eye [344] . Acute acqui red comi tant ET i n chi l dhood may also occur
w it h cent ral nervous syst em t umors, especially brainst em and cerebellar t umors
and t umors of t he corpus callosum, and w it h Chiari I malf ormat ion [489] . The
mechanism of acut e acquired comit ant ET is unknow n. O t her et iologies of
increased or sust ained spasm of t he near ref lex include t halamic ET, t halamic
hemorrhage, pineal t umor, Wernicke-Korsakoff syndrome, post erior f ossa
lesions, Arnold-Chiari malf ormat ion, encephalit is, vert ebrobasilar ischemia,
met abolic abnormalit ies, including phenyt oin int oxicat ion and hepat ic
encephalopat hy, Miller-Fisher syndrome, and int ernuclear opht halmoplegia [16,
480, 622, 771] .
Weakness of di vergence is charact erized by int ermit t ent or const ant ET at
dist ance w it h f usion at near [486, 834] . When ET at dist ance due t o divergence
impairment occurs in an ot herw ise healt hy individual, it is ref erred t o as
“di vergence i nsuf f i ci ency, ” w hereas it is called “di vergence paral ysi s. ” w hen it
occurs associat ed w it h neurologic disease. Divergence paralysis is associat ed
w it h diverse cent ral nervous syst em disease and can be mimicked by myast henia
gravis [486] . Alt hough of t en described w it h post erior f ossa disease, divergence
paralysis is a nonlocalizing cause of horizont al diplopia and, t heref ore, mult iple
or diff usely dist ribut ed neural st ruct ures may govern divergence [486] . For
example, divergence paralysis may be seen w it h low er pont ine lesions; af t er
t rauma, lumbar punct ure, or epidural block; w it h encephalit is, demyelinat ing
disease, neurosyphilis, or t umors in and around t he cerebellum; w it h increased
int racranial pressure; w it h brainst em ischemia; w it h acut e lymphocyt ic leukemia–
Acut e Lymphocyt ic Leukemia (ALL); as an init ial sign of Miller-Fisher syndrome;
w it h Machado-Joseph disease; or associat ed w it h diazepam use [480, 590] .
Gaze Palsies
An underst anding of t he syst ems t hat coordinat e eye movement s clarif ies w hy
lesions at diff erent levels of t he brain spare some syst ems w hile aff ect ing
ot hers. The result ing pat t ern of eye movement s is helpf ul f or localizat ion of
lesions. Alt ernat ive pat hw ays account f or diff erent ial severit y of t he def icit
relat ed t o a single lesion or t o several lesions. For inst ance, a unilat eral lesion in
t he f ront al eye f ield (area 8) causes only t ransient gaze palsy, but simult aneous
involvement of t he ipsilat eral SC causes severe impairment of cont ralat eral
saccadic eye movement s.
Conjugate Gaze Palsies

A conjugat e gaze palsy is one in w hich bot h eyes are symmet rically rest rict ed in
t heir excursion t o one side, up, or dow n.
Horizontal Conjugate Gaze Palsy

Unilat eral rest rict ion of volunt ary gaze t o one side is most of t en due t o
cont ralat eral f ront al or ipsilat eral pont ine damage.
Fron tal Lesion s

Front al lesions causing a gaze palsy t end t o be rat her acut e, and t he result ing
palsy is t ransient . I n t he acut e phase, t he pat ient generally has a hemiparesis

and “looks t ow ard t he lesion, ” aw ay f rom t he hemiparesis (Prevost or Vul pi an
si gn). The gaze palsy can be overcome w it h t he oculocephalic maneuver or
caloric st imulat ion. I f t he process, most of t en a st roke, evolves f avorably, t he
gaze palsy resolves in a f ew days, alt hough impaired init iat ion and hypomet ria of
volunt ary saccades may remain. Af t er clinical disappearance of t he conjugat e
eye deviat ion, disorders of saccades (cont ralat eral more t han ipsilat eral) and
smoot h pursuit (ipsilat eral more t han cont ralat eral) may st ill be demonst rat ed f or
at least six mont hs in most pat ient s [778] . I n general, t he larger t he lesion, t he
more persist ent t he conjugat e deviat ion. Prolonged eye deviat ion af t er st roke
of t en implies preexist ing damage t o t he cont ralat eral f ront al region and,
t heref ore, early recovery of t he gaze palsy may w ell be mediat ed by t he
cont ralat eral unaff ect ed eye f ield [736] . Sust ained horizont al gaze is more
common af t er large st rokes aff ect ing t he post -Rolandic cort ex or subcort ical
f ront opariet al region and t he I C. Lesions in t he corona radiat a adjacent t o t he
genu of t he I C may cause cont ralat eral select ive saccadic palsy (associat ed w it h
cont ralat eral supranuclear f acio-palat o-pharyngeal paresis w it h no t ongue or
limb w eakness) suggest ing t hat t he some of t he descending pat hw ays f rom t he
FEF may pass t hrough t he genu of t he I C in parallel w it h t he cort icobulbar t ract
[ 258] .
Af t er a hemispheric lesion, t here may be a t endency f or t he eyes t o become
deviat ed t ow ard t he side of t he hemiparesis w it h f orced lid closure (Cogan's
spast icit y of conjugat e gaze). This f inding can be elicit ed by asking t he pat ient t o
close his eyes w hile t he eyelids are kept f orcibly open, t ends t o be of
lat eralizing value, and is seen more commonly w it h pariet ot emporal lesions
[ 745] .
Lesions of t he FEF may produce an ipsilat eral horizont al gaze deviat ion t hat
resolves. Cont ralat eral volunt ary saccades are hypomet ric and impaired smoot h
pursuit is not ed t ow ard t he side of t he lesion. Lesions of t he SEF cause
impairment of t he abilit y t o make a remembered sequence of saccades t o visible
t arget s, w hile dorsolat eral pref ront al lesions cause impaired perf ormance t o
ant isaccade t asks.
Epi l eptogeni c l esi ons in t he FEFs may cause t ransient deviat ion of t he eyes and
head t o t he cont ralat eral side (t he pat ient t hen “looks” aw ay f rom t he lesion)
[ 287] . How ever, in most cases, as soon as t he f ocal seizure ceases, t he pat ient
t ends t o “look” t o t he involved side. I psiversive head and eye movement s during
a seizure are more likely w it h t emporal or f ront al epilept if orm f oci and less likely
w it h occipit al f oci [519, 655, 659, 838] . Maint enance of aw areness during
versive movement s alw ays indicat es a cont ralat eral f ocus and an origin f rom t he
f ront al lobe in most inst ances [519] . I nit ial f orced t urning (versive) head and eye
movement s (occurring in t he f irst 10 seconds af t er seizure onset ) usually
correspond t o a cont ralat eral epilept if orm f ocus, but t hese init ial cont raversive
movement s may be f ollow ed by lat e ipsiversive nonf orced movement s during t he
secondary generalizat ion of t he epilept if orm act ivit y [423, 846, 847] . Theref ore,
t he l ate version, unlike t he init ial version, is f requent ly ipsilat eral and cannot be
assumed t o indicat e seizure onset in t he cont ralat eral hemisphere. Turning
movement s have been classif ied as eit her versi ve (unquest ionably f orced and
involunt ary, result ing in sust ained unilat eral posit ioning) or nonversi ve (mild,
unsust ained, w andering, or seemingly volunt ary movement s) [846, 847] .
Cont ralat eral versive head and eye movement s occur during seizures, but
ipsilat eral versive movement s do not . Nonversive lat eral head and eye
movement s occur ipsilat erally and cont ralat erally w it h equal f requency and are
not of localizing signif icance. Theref ore, t rue versive head and eye movement s
are t hought t o be a reliable localizing sign [423, 846, 847] .
Wit h f ront al lesions, w hen opt okinet ic nyst agmus is elicit ed, t he quick component
t ow ard t he side cont ralat eral t o t he lesion is impaired, but smoot h pursuit is
preserved if t he lesion spares t he pariet al lobe.
Parietal Lesion s
Acut e pariet al lesions may cause ipsilat eral horizont al gaze pref erence. Wit h
right -sided lesions, t here is also cont ralat eral inat t ent ion. The lat ency of visually
guided saccades t o t arget s present ed in eit her visual hemif ield is increased w it h
right -sided lesions, w hile lef t -sided lesions cause delay in only cont ralat eral
saccades. Bilat eral pariet al lesions cause Balint 's syndrome (see Chapt er 20).
T h alamic Lesion s
Hemorrhages deep in a cerebral hemisphere, part icularly t hose involving t he
medial t halamus, can also cause eye deviat ion t o t he side of t he hemiparesis,
opposit e t he lesion (“wrong way eyes”). The reason f or t his cont raversive
deviat ion is unknow n but it may be an irrit at ive phenomena because t he
int ralaminar t halamic nuclei have a role in t he product ion of cont ralat eral
saccades. O t hers have post ulat ed t hat involvement of t he descending ocular
mot or pat hw ays f rom t he cont ralat eral hemisphere at t he midbrain level is t he
most probable explanat ion f or t his phenomenon [524, 777] . Thalamic lesions,
especially hemorrhage, may also be associat ed w it h t onic dow nw ard and inw ard
deviat ion of t he
eyes (t he pat ient s “peer at t he t ip of t he nose”), w it h miosis, likely due t o
irrit at ion or dest ruct ion of t he neural st ruct ures involved in t he vergence and
vert ical upw ard gaze in t he mesodiencephalon [148] . Skew deviat ion and ET f rom
abduct ion def icit may be involved in some pat ient s. Caudal t halamic lesions may
also be associat ed w it h ET (t halamic esot ropia), w it hout dow nw ard deviat ion,
due t o convergence excess. Dow ngaze paralysis and impaired horizont al
saccades, report ed w it h t halamic inf arct ion, is probably due t o t he involvement
of t he riMLF and midbrain descending smoot h pursuit pat hw ays, respect ively
Mesen ceph alic Lesion s

O ccasionally, mesencephalic lesions may cause horizont al gaze palsies.
Unilat eral paramedian involvement of t he midbrain t egment um may cause paresis
of cont ralat eral saccades (probably due t o disrupt ion of t he cort icof ugal
t ranst halamic and/ or t he pref ront al ocular mot or bundle) associat ed w it h
monocular paralysis of adduct ion in t he ipsilat eral eye (nuclear or int ernuclear
f rom a lesion of t he MLF) and conjugat e paresis of ipsilat eral smoot h pursuit
[ 866, 867, 868, 869, 870] . The horizont al vest ibulo-ocular ref lex is spared.
These mesencephalic t egment al lesions likely disrupt pref ront al cort icof ugal
pat hw ays, colliculof ugal pat hw ays, and smoot h pursuit pat hw ays [ 866, 867, 868,
869, 870] . Also, pat ient s w it h unilat eral inf arct ions of t he midbrain–diencephalic
junct ion may have supranuclear cont ralat eral gaze palsies associat ed w it h
ipsilat eral oculomot or palsies [512] . Large midbrain lesions may lead t o
complet e opht halmoplegia. Lesions conf ined t o t he SC are rare but may cause
def ect s in t he lat ency and accuracy f or cont ralat eral horizont al saccades and
impaired perf ormance in ant isaccade t asks.
Pon tin e Lesion s

As not ed earlier, t he abducens nucleus receives (a) excit at ory and inhibit ory
f ibers f rom t he VN (vest ibular, opt okinet ic, and pursuit s eye movement s), (b)
PPRF connect ions (saccades), (c) f ibers f rom t he nucleus proposit us
hypoglossi/ MVN (gaze holding), and (d) project ions f rom t he cont ralat eral MR
nucleus subdivision (oculomot or int ernuclear neurons t hat coordinat e
convergence) [480] . I n pont ine lesions aff ect ing t he abducens nucl eus, t he eyes
look t ow ard t he hemiparesis (alt hough hemiparesis is an inconst ant f inding) and
cannot of t en be brought t o t he paret ic side using t he doll's eye maneuver or
ipsilat eral cold caloric st imulat ion. Vergence is spared, since t hese movement s
depend on project ions t hat pass direct ly t o MR mot oneurons. Saccades, pursuit ,
opt okinet ic, and vest ibular movement s are all impaired t ow ard t he side of t he
lesion (nondissociat ed ipsilat eral horizont al gaze palsy) [193] ; t heref ore, lesions
of t he abducens nucleus cause ipsilat eral palsy of conjugat e gaze. Saccades
direct ed t ow ard t he side of t he lesion are present in t he cont ralat eral hemif ield
of movement , but are slow because t hey now depend solely on project ions t o t he
int act abducens nucleus f rom t he I BN of t he cont ralat eral medullary ret icular
f ormat ion, and saccadic peak velocit y is now a f unct ion of ant agonist muscle
relaxat ion rat her t han ant agonist cont ract ion [258] . Horizont al gaze-evoked
nyst agmus may be evident on looking cont ralat erally, probably due t o
involvement of f ibers f rom t he MVN (w hich provide an eye posit ion signal t o t he
cont ralat eral abducens nucleus) or due t o involvement of t he cell groups of t he
PMT (w hich may cont ribut e t o horizont al gaze holding t hrough project ions t o t he
cerebellum). An ipsilat eral f acial nerve palsy of t en accompanies abducens
nuclear lesions; how ever, isolat ed acquired unilat eral horizont al gaze paresis
(w it hout CN V or VI I involvement ) may occur f rom a put at ive lesion of t he
abducens nucleus [531] . Bilat eral horizont al gaze palsies may occur w it h
bilat eral lesions [718] . Horizont al pont ine gaze palsy may be associat ed w it h
ipsilat eral ET [710] .
When all rapid eye movement s (saccades and quick phases of nyst agmus)
ipsilat eral t o t he lesion are abolished w it h preserved ipsilat eral vest ibulo-ocular
response, smoot h pursuit , and gaze-holding abilit y, t he PPRF is involved
(dissociat ed ipsilat eral horizont al conjugat e gaze palsy). Acut ely, t he eyes are
deviat ed cont ralat erally. I psilat erally direct ed saccades f rom t he opposit e f ield
are small and slow or even absent and do not carry t he eyes past t he midline;
t his occurs w it h PPRF lesions because bot h EBNs and I BNs are impaired and
t here is no longer any inhibit ion of t he ant agonist muscles cont rolled by t he
abducens nucleus on t he opposit e side (vs. abducens nucleus lesions) [258] .
Nyst agmus may occur w hen gaze is direct ed int o t he cont ralat eral f ield of
movement w it h t he quick phase aw ay f rom t he side of t he lesion. I n some
pat ient s w it h PPRF lesions, vest ibular st imulat ion can only drive t he cont ralat eral
adduct ing eye int o t he ipsilat eral f ield w it hout any drive of t he ipsilat eral
abduct ing eye. This occurs because t he abducens f ascicle t ravels t hrough t he
PPRF in it s course t hrough t he pons so t hat a PPRF lesion may be associat ed
w it h an ipsilat eral abducens nerve palsy (t he abducens nucleus is spared). I n
some pat ient s w it h PPRF lesions, axons conveying vest ibular and pursuit input t o
t he abducens nucleus may also be damaged and, t heref ore, occasionally
ipsilat eral smoot h pursuit and vest ibular eye movement s may be impaired.
Loss of horizont al volunt ary eye movement s may occur as a paraneoplast ic

phenomenon associat ed w it h severe, persist ent muscle spasms of t he f ace, jaw,
and pharynx [48] . Prost at e carcinoma has been associat ed w it h t his syndrome,
probably due t o an aut oimmune process t hat damages a subpopulat ion of
brainst em neurons crit ical f or horizont al eye movement s and recurrent inhibit ion
of bulbar nuclei.
Sel ecti ve saccadi c pal sy volunt ary saccades, in bot h horizont al and vert ical
planes, are slow and t he quick phases of vest ibular and opt okinet ic nyst agmus
are absent , w hile smoot h pursuit , t he vest ibulo-ocular ref lex, t he abilit y t o hold
st eady eccent ric gaze, and vergence eye movement s are preserved [324, 573] .
Pat hologic st udy revealed lesions involving t he median and PPRF and median
basis pont is w it h sparing of t he rost ral mesencephalon and t he riMLF [324] .
These f indings suggest t hat t he riMLF is dependent on input s f rom t he PPRF f or
t he programming of normal vert ical saccades [324] . I t may be t hat lesions
involving t he PPRF may also damage omnipause neurons t hat project t o t he
riMLF and, t heref ore, vert ical as w ell as horizont al saccades are slow ed.
Unilat eral lesions of t he pont ine t egment um may result in slow ed ipsilat eral
horizont al saccades associat ed w it h abnormal vert ical saccades [388] .
At t empt ed vert ical saccades in t hese pat ient s are misdirect ed obliquely, aw ay
f rom t he side of t he lesion, and vert ical component s are prolonged. Unilat eral
damage t o EBNs and pause cells in t he medial part of t he caudal PPRF may
cause t hese abnormal vert ical and oblique saccades.
A pseudohori zontal gaze pal sy may occur w it h pont ine lesions damaging t he
MLF on one side (see subsequent t ext ) and t he cont ralat eral abducens nerve
f ascicle. This pseudohorizont al gaze palsy should be suspect ed if t he gaze palsy
is asymmet ric, usually w it h t he adduct ing eye more rest rict ed t han t he abduct ing
eye.
Peri odi c al ternati ng gaze (PAG ) is composed of (a) cyclic conjugat e lat eral
deviat ion of t he eyes, usually w it h compensat ory head t urning t o t he opposit e
side f or 1 t o 2 minut es, (b) a midline changeover period of 10 t o 15 seconds,
f ollow ed by (c) conjugat e deviat ion of t he eyes t o t he ot her side w it h
compensat ory head t urning f or 1 t o 2 minut es [472] . Wit h t he except ion of one
case of occipit al encephalocele, all cases of t his rare condit ion st udied
radiographically or pat hologically have demonst rat ed disease in t he post erior
f ossa (e. g. , pont ine damage, post erior f ossa ischemia, spinocerebellar
degenerat ion, cerebellar medulloblast oma, Arnold-Chiari malf ormat ion, cerebellar
dysgenesis, et c. ), especially aff ect ing t he inf erior cerebellar vermis [472] .
Vertical Conjugate Gaze Palsy

Non domin an t Hemisph eral an d T h alamic Lesion s
Bilat eral pt osis and upgaze palsy has been described w it h right hemispheric
lesions [39] . Thal ami c lesions may be associat ed w it h vert ical gaze palsies
[ 801] . Alt hough most of t hese lesions also involve midbrain st ruct ures involved
w it h vert ical gaze, in some pat ient s no midbrain involvement is not ed on
neuroimaging suggest ing involvement of supranuclear input s [157, 191] .
Midbrain Lesion s
Uni l ateral l esi ons of the ri MLF cause slow ing of dow nw ard saccades. Each
riMLF cont ains burst neurons f or bot h upw ard and dow nw ard movement s but
project ions t o mot oneurons innervat ing depressors are ipsilat eral w hile t hose
innervat ing elevat ors are probably bilat eral. A unilat eral lesion of t he riMLF may
occasionally cause combined up- and dow ngaze palsies, perhaps by disrupt ing
bilat eral upgaze excit at ory and inhibit ory input s and unilat eral dow ngaze
excit at ory input s [91] . A def ect of t orsional saccades is also produced w it h
unilat eral riMLF lesions; f or example, w it h a right riMLF lesion, t orsional quick
phases in a clockw ise (pat ient 's view ) are lost (i. e. , ext orsion of t he right eye
and int orsion of t he lef t eye) [650] . Unilat eral riMLF lesions can be det ect ed at
t he bedside if t orsional quick phases are absent during ipsidirect ional head
rot at ions in roll [82] . There is also a cont ralesional t orsional deviat ion w it h
t orsional nyst agmus beat ing cont ralesionally. Bi l ateral ri MLF l esi ons cause
def icit s of eit her dow nw ard saccades or dow nw ard and upw ard saccades [298,
349, 584] . Vert ical gaze holding, pursuit , and vest ibulo-ocular ref lexes are
preserved. Lesions of t he riMLF are usually inf arct s in t he dist ribut ion of t he
post erior t halamosubt halamic paramedian art ery t hat arises bet w een t he
bif urcat ion of t he basilar art ery and t he origin of t he post erior communicat ing
art ery, w it h a single vessel of t en supplying bot h riMLFs. Somnolence and
memory impairment of t en coexist because of damage t o t he medial t halamic
nuclei.
Lesions of t he I NC (t he neural int egrat or f or upw ard gaze) cause impaired
vert ical and t orsional gaze holding w it h large lesions causing severe limit at ion of
vert ical gaze, especially upw ard. I t is possible t hat such lesions also aff ect ot her
midbrain st ruct ures, such as t he nucleus of t he PC t hat cont ribut es t o t he cont rol
of upw ard gaze. Bilat eral lesions cause reduced range of all vert ical eye
movement s but saccades are not slow ed. Unilat eral lesions of t he I NC also
cause an ocular t ilt
react ion–O cular Tilt React ion (O TR) w it h t orsional nyst agmus beat ing
ipsilesionally (see subsequent t ext ), w hile bilat eral lesions cause upbeat
nyst agmus–Upbeat Nyst agmus (UBN) and neck ret rof lexion.
The PC is t he rout e by w hich t he I NC project s t o ocular mot oneurons.
I nact ivat ion of t he PC causes vert ical gaze-evoked nyst agmus, but dest ruct ive
lesions cause a more prof ound def ect of vert ical gaze, probably because of t he
involvement of t he nucleus of t he PC [82] . Lesions of t he PC cause vert ical gaze
impairment aff ect ing all classes of vert ical eye movement s, especially upw ard
gaze [480] . The const ellat ion of f indings caused by lesions in t his locat ion has
been variously designat ed as t he Pari naud's syndrome, Syl vi an aqueduct
syndrome, pretectal syndrome, dorsal mi dbrai n syndrome, and Koerber-Sal us-
El schni g syndrome [ 411] . The syndrome probably ref lect s damage t o axon
project ions of t he I NC and damage t o t he nucleus of t he PC. Unilat eral midbrain
lesions may cause t he same syndrome by damaging aff erent and eff erent
connect ions of t he PC [349, 642] .
Wit h t he dorsal mi dbrai n syndrome, t here is impairment of all upw ard eye
movement s (alt hough t he vest ibulo-ocular ref lex and Bell's phenomenon may
somet imes be spared). Dow ngaze saccades and smoot h pursuit may be
impaired, but dow nw ard vest ibulo-ocular movement s are spared. A sign of dorsal
midbrain compression in hydrocephalic inf ant s is a t onic dow nw ard deviat ion of
t he eyes, w hile t he ret ract ed eyelids expose t he epicorneal sclera (“setti ng sun”
si gn). Dow nbeat ing nyst agmus may be present . The upper eyelid may be
ret ract ed, baring t he sclera above t he cornea (Col l i er's “tucked l i d” si gn); t his
sign is probably due t o damage t o t he PC levat or inhibit ory f ibers or is a
manif est at ion of normal levat or—SR synkinesis. Bilat eral pt osis may result w hen
t he lesion ext ends vent rally t o involve t he caudal cent ral nucleus of CN I I I . The
pupils are large and react poorly t o light , but t he near response is spared (light -
near dissociat ion). O ccasionally, skew deviat ion w it h t he higher eye on t he side
of t he lesion is not ed. Convergence and divergence are of t en impaired. I n some
pat ient s, a convergence spasm may result in slow or rest rict ed abduct ion
(“mi dbrai n pseudo-si xth”) during horizont al ref ixat ions [627] . At t empt ed upgaze
may result in convergence-ret ract ion nyst agmus, w it h quick adduct ing-ret ract ion
jerks. This phenomenon can be elicit ed at t he bedside by having t he pat ient
w at ch a dow nw ard-moving opt okinet ic drum. I n t his case, t he normal upw ard
correct ive saccades are replaced by convergence-ret ract ory nyst agmus, w hich is
not made by convergence movement s but by opposed adduct ing saccades at
least in some cases. As ment ioned earlier, t rue convergence is of t en absent . The
ret ract ion of t he eye int o t he orbit result s f rom irregular cof iring f rom several
ext raocular muscles, perhaps due t o impairment of recurrent inhibit ion w it h t he
oculomot or subnuclei or abnormal vergence act ivit y [627, 637] . Fixat ion
inst abilit y w it h square-w ave jerks may also be not ed.
Tumors are most of t en responsible f or damage of t he dorsal midbrain [411] .
Hydrocephalus is anot her common et iology, especially w hen dilat at ion of t he
t hird vent ricle and aqueduct or enlargement of t he suprapineal recess cause
pressure on and def ormit y of t he PC. Pat ient s w it h shunt ed hydrocephalus may
develop f eat ures of t he pret ect al syndrome w it h shunt dysf unct ion even w it hout
any dilat ion of t he vent ricular syst em or elevat ion of int racranial pressure;
t heref ore, t he observat ion of t hese clinical f eat ures provides a sensit ive index of
shunt dysf unct ion regardless of vent ricular size or isolat ed measurement s of
int racranial pressure [87, 156] . Less likely causes of pret ect al syndrome include
t halamic or midbrain hemorrhage or inf arct ion, hypoxia, mult iple sclerosis,
t rauma, lipid st orage diseases, Wilson's disease, drugs (barbit urat es,
carbamazepine, neurolept ics), Whipple's disease, syphilis, and t uberculosis [15,
465, 466, 471, 480] . A posit ion-dependent Parinaud's syndrome (i. e. , t he
syndrome w as manif est only w it h changes in head posit ion) has been described
w it h a subdural f luid collect ion over t he cerebellar hemisphere [652] . Upw ard
gaze is of t en limit ed in Parkinson's disease and may be rarely aff ect ed w it h
vit amin B12 def iciency [411] .
Convergence-ret ract ory nyst agmus may be mimicked by bilat eral dyst hyroid
orbit opat hy w it h bilat eral involvement of bot h medial rect i and inf erior rect i;
saccadic upgaze at t empt s may cause convergence and ret ract ion due t o
limit at ion of eye movement s [128] . O t her peripheral eye movement abnormalit ies
t hat may mimic upgaze palsy or even convergence nyst agmus include Lambert -
Eat on myast henic syndrome [175] and Fisher syndrome [418] .
In summary, select ive paralysis of dow nw ard saccades may occur w it h bilat eral
riMLF lesions, w hile dow ngaze paralysis aff ect ing all t ypes of eye movement s
may occur w it h I NC or PC lesions [349, 362] . Pseudopt osis on at t empt ed
dow nw ard gaze may be not ed as t he levat ors relax. Paralysis of upgaze
aff ect ing all t ypes of eye movement s may occur w it h lesions of t he PC and I NC.
Combined upgaze and dow ngaze palsies f or
saccades only is due t o bilat eral riMLF lesions, w hile combined upgaze and
dow ngaze palsies f or all eye movement s are due t o damage t o bot h t he I NCs or
t he PC.
Dow ngaze is involved early in PSP [ 249] . The init ial ocular mot or def icit in PSP
consist s of slow ing of vert ical saccades and quick phases, especially dow nw ard,
w it h preserved range of movement . Lat er, vert ical saccades and quick phases
are lost . Pat ient s w it h PSP make errors w hen t hey are required t o look in t he
opposit e direct ion t o t hat in w hich a t arget suddenly appears (ant isaccade t ask).
Bell's phenomenon is usually absent . At a st age w hen f ull vert ical excursions are
st ill present , some pat ient s w it h PSP display an inabilit y t o produce pure vert ical
saccades along a st raight line in t he midline. I nst ead, t hey can only accomplish
vert ical saccades by moving t heir eyes in a lat eral arc (t he “round the houses”
si gn) [629, 667] . Horizont al eye movement s may also be impaired (saccades and
pursuit ), and square-w ave jerks inhibit f ixat ion. I mpaired vert ical smoot h pursuit
occurs lat er, but vest ibulo-ocular ref lexes are preserved. Vert ical saccade
abnormalit ies are t hought t o be due t o involvement of t he riMLF, square-w ave
jerks due t o SC damage, abnormal smoot h pursuit due t o damage of t he
dorsolat eral pont ine nuclei, and impaired ant isaccade responses due t o f ront al
lobe dysf unct ion or involvement of t he subst ant ia nigra pars ret iculat a, w hich
normally suppresses saccades. Convergence is of t en impaired, eye-opening
apraxia may occur, and, event ually, complet e opht halmoplegia may develop.
O t her lid abnormalit ies include blepharospam, eye-closing apraxia, lid ret ract ion,
and lid lag. I n some pat ient s, an eye movement disorder resembling int ernuclear
opht halmoplegia (see subsequent t ext ) may occur, alt hough vest ibular st imulat ion
may overcome t he limit ed adduct ion.
Averbach-Heller et al. report ed t he case of a parkinsonian syndrome w it h
abnormal vert ical eye movement s t hat mimicked PSP but t hat w as due t o
Whi ppl e's di sease [ 37] . Eye movement recordings revealed marked slow ing of
upw ard saccades, moderat e slow ing of dow nw ard saccades, a f ull range of
volunt ary vert ical eye movement s, curved t raject ories of oblique saccades, and
absence of square-w ave jerks. These f eat ures are at ypical f or PSP, in w hich t he
range of volunt ary vert ical eye movement s is charact erist ically limit ed, horizont al
smoot h pursuit is commonly impaired, and f ixat ion is disrupt ed by square-w ave
jerks. Also, in PSP dow nw ard eye movement s are more severely aff ect ed. O t her
disease processes w it h eye movement abnormalit ies resembling PSP include
idiopat hic st riopallidodent at e calcif icat ions and aut osomal dominant parkinsonism
and dement ia w it h pallidopont onigral degenerat ion. Cort ical–basal ganglionic
degenerat ion is associat ed w it h increased saccadic lat encies but does not cause
slow ing of saccades. Parkinson's disease seldom produces slow saccades unt il
lat e in t he course. Creut zf eldt -Jacob disease slow s saccades bot h in a vert ical
and horizont al plane. I n mult iple syst ems at rophy, saccades are not slow but are
hypomet ric. Diff use Lew y body disease may present w it h supranuclear vert ical
and horizont al opht halmoplegia [231] .
O t her causes of progressi ve impairment of dow ngaze include Niemann-Pick C
disease and variant , adult -onset hexosaminidase A def iciency,
olivopont ocerebellar degenerat ion, at axia-t elangiect asia, Wilson's disease,
Hunt ingt on's disease, Whipple's disease, Parkinson's disease (rare), and
Hallervorden-Spat z disease (rare) [236, 327] . The DAF syndrome is an acronym
suggest ed f or a group of pat ient s w it h prominent signs of dow ngaze paralysis,
at axia/ at het osis, and f oam cells; it is t hought t o be a variant of Niemann-Pick
disease (e. g. , sea-blue hist iocyt osis syndrome or juvenile dyst onic lipidosis)
[ 236] .
Parki nson's di sease may be associat ed w it h square-w ave jerks, hypomet ria of
horizont al and vert ical (especially upw ard) saccades w it h normal saccadic
velocit y (except in advanced cases), impaired smoot h pursuit , impaired
convergence, and lid ret ract ion and lag (vest ibular eye movement s are spared).
Pallidot omy may induce square-w ave jerks in parkinsonian pat ient s.
O t her eye abnormalit ies in pat ient s w it h Parkinson's disease include complaint s
suggest ing ocular surf ace irrit at ion, alt ered t ear f ilm w it h dry eyes, visual
hallucinat ions, blepharospasm, decreased blink rat e, and decreased
convergence amplit udes w it h convergence insuff iciency [84] . Hunti ngton's
di sease may be associat ed w it h diff icult ies in init iat ing saccades (prolonged
lat ency), w hich is of t en f acilit at ed by an associat ed head t hrust or eye blink.
O t her f indings include impairment in t he perf ormance of ant isaccade t asks, slow
saccades, especially vert ically, and impaired smoot h pursuit (t he VO R and gaze
holding are preserved). Dent at orubropallidoluysian at rophy or Haw River disease
may also cause slow saccades. Ataxi a-tel angi ectasi a may be associat ed w it h
abnormalit ies in t he syst ems t hat maint ain f ixat ion and shif t gaze including
abnormal ref lexive and volunt ary saccades (charact erized by prolonged lat ency,
hypomet ric amplit ude, and t he use of head movement s t o init iat e gaze shif t s) and
impaired f ixat ion [490] . The abnormalit ies of image
st abilizat ion most likely result f rom dysf unct ion in t he cerebellar f locculus and
paraf locculus, w hile saccadic abnormalit ies may result f rom abnormal
supranuclear cont rol of t he SC result ing f rom dysf unct ion in t he cerebellar vermis
or t he basal ganglia.
Kuf or Rakeb di sease (aut osomal recessive, levodopa-responsive parkinsonism
w it h pyramidal degenerat ion, supranuclear gaze palsy, and dement ia) may be
associat ed w it h hypomet ric, slow vert ical saccades and limit at ion of up- and
dow ngaze [ 841A] . Associat ed f eat ures include supranuclear gaze palsy; acut e L-
dopa-responsive oculogyric dyst onic spasms; f acial, f aucial, and f inger mini
myoclonus; visual hallucinat ions; L-dopa-provoked mot or f luct uat ions; and
w idespread cerebral at rophy on neuroimaging.
I n a consecut ive series of 50 post resuscit at ion comat ose pat ient s, 28 (56. 0%)
developed t onic upw ard or dow nw ard eye deviat ion [380] . The aut hors
suggest ed t hat bot h t he upw ard and t he dow nw ard deviat ions result ed f rom
diff use cerebrocerebellar damage sparing t he brainst em. Upw ard deviat ion is an
early sign, w hereas dow nw ard deviat ion appears lat er and generally implies a
t ransit ion t o t he veget at ive st at e.
Ocu logyric Crisis

O culogyric crises are episodic, spasmodic, conjugat e ocular deviat ions, usually
occurring in an upw ard and lat eral (rarely dow nw ard or lat eral) direct ion. The
eye deviat ion is of t en accompanied by ment al changes, especially disorders of
at t ent ion in w hich pat hologic f ixat ion of a t hought (obsessive, persist ent
t hought s) occurs [476] . This disorder of mood may precede or accompany t he
ocular deviat ion. The disorder may be due t o impairment of t he vert ical neural
int egrat or. The crises may be accompanied by dyst onic or dyskinet ic movement s
such as t ongue prot rusion, lip smacking, blepharospasm, choreoat het osis, and
ant erocollis. O culogyric crises may be caused by encephalit is let hargica,
degenerat ive diseases, such as f amilial parkinsonism-dement ia, Chédiak-Higashi
syndrome, Touret t e's syndrome, head t rauma, neurosyphilis, mult iple sclerosis,
at axia-t elangiect asia, brainst em encephalit is, t hird vent ricular glioma,
st riat ocapsular inf arct ion, bilat eral put aminal hemorrhage, or medicat ions such
as neurolept ics (e. g. , haloperidol and piperazine phenot hiazines), lit hium,
t et rabenazine, cet irizine, and carbamazepine [211, 248, 494] . O culogyric crisis
has also been described as a paraneoplast ic process w it h t est icular cancer
associat ed w it h ant i-Ta ant ibodies [77] and may be t he init ial manif est at ion of
Wilson's disease [469] .
Dysconjugate Gaze Palsies

Horizontal Dysconjugate Gaze Palsies
Medial Lon gitu din al Fascicu lu s Syn drome or In tern u clear
Oph th almoplegia
Clinically, t his syndrome is charact erized by adduct ion w eakness on t he side of
t he MLF lesion and monocular nyst agmus of t he abduct ing eye [252] . How ever,
unless t he lesion is quit e high, reaching t he midbrain, convergence is preserved.
O f t en pat ient s w it h int ernuclear opht halmoplegia (I NO ) have no visual sympt oms
but ot hers may complain of diplopia (due t o limit at ion of adduct ion or skew
deviat ion) or oscillopsia (in t he horizont al plane due t o t he adduct ion lag or t he
abduct ion nyst agmus; in t he vert ical plane it may occur during head movement s
and is caused by a def icient vert ical vest ibulo-ocular ref lex). Adduct ion
w eakness in I NO result s f rom disrupt ion of t he signals carried by t he MLF—
signals coming f rom t he int ernuclear abducens nucleus and dest ined f or t he
oculomot or nucleus. Alt hough t he w eakness of t he MR aff ect s all t ypes of
conjugat e eye movement s, it is most evident during saccades and t he “adduct ion
lag” is best brought out during opt okinet ic t est ing using a t ape or drum [722] .
For example, w it h a right I NO w hen t he drum is rot at ed t o t he right t he amplit ude
and velocit y of t he adduct ing quick phase of t he right eye is smaller and slow er
t han t hat of t he abduct ing saccades in t he lef t eye. When I NO is due t o
demyelinat ing disease, t here may be a discrepancy bet w een t he involvement of
saccades and ot her movement s because demyelinat ed f ibers cannot carry t he
high-f requency discharges required during t he saccadic pulse.
I NO is of t en associat ed w it h skew deviat ion (see subsequent t ext ) w it h t he
higher eye on t he side of t he lesion, likely ref lect ing imbalance of ot olit h out put s
t hat cross in t he medulla and ascend in t he MLF. The pat hogenesis of t he
nyst agmus in t he abduct ing eye is unclear but is likely a normal adapt ive process
t hat helps overcome t he adduct ing w eakness of t he f ellow eye [ 869] . Theref ore,
abduct ion nyst agmus in I NO depends on t he MR paresis and is presumably
init iat ed by a visual error signal [762] . Vert ical gaze-evoked nyst agmus and
impaired vest ibular and pursuit vert ical eye movement s and vert ical gaze holding
may occur, especially w it h bilat eral I NO , because of t he int errupt ion of MLF
axons carrying vert ical vest ibular and smoot h pursuit signals [480] . Vert ical
saccades are spared. I NO may be associat ed w it h ipsilat eral DBN and
cont ralat eral incyclorot at ory (t orsional) nyst agmus ref lect ing t hat most
post erior SCC cent ral f ibers are conveyed t hrough t he MLF, w hile some ant erior
SCC pat hw ays are not [509] . I psilesional t orsional nyst agmus [577] and jerky
see-saw nyst agmus [581] may also occur. Unilat eral I NO may be associat ed w it h
t ransient (disappearing w it hin 3 days) t orsional nyst agmus, w hich is clockw ise
(examiner's view ) in cases of lef t I NO and count erclockw ise in right I NO [228] .
This t orsional nyst agmus is t hought t o be due t o a decrease in vert ical SCC input
t o t he t rochlear and oculomot or nuclei ow ing t o t he MLF lesion, w hich result s in
t onic t orsional imbalance t hat is correct ed by a t orsional saccade generat ed in
t he int act ipsilat eral rost ral int erst it ial nucleus of t he MLF.
Bilat eral I NO is most of t en seen w it h mult iple sclerosis and ischemic lesions
[ 272, 417, 426] . Unilat eral I NO may result f rom brainst em inf arct ion [221, 426] .
Alt hough bilat eral I NO is more common w it h mult iple sclerosis t han w it h vascular
insult s, bilat eral I NO may occur w it h st roke as w ell as many ot her pat hologic
processes and, t heref ore, t he presence of a unilat eral or bilat eral I NO cannot be
used as a diff erent ial f eat ure f or et iologic diagnosis. For example, in a series of
100 pat ient s w it h mult iple sclerosis, 34 had I NO , w hich w as bilat eral in 14 and
unilat eral in 20 [558] . I n anot her st udy of 51 pat ient s w it h I NO , 28 had mult iple
sclerosis and 23 had inf arct ion; I NO w as bilat eral in 23 pat ient s and unilat eral in
28 [352] . Most pat ient s w it h nut rit ional, met abolic, degenerat ive, and drug-
induced int oxicat ion have bilat eral I NO s. O t her causes of I NO include Wernicke's
encephalopat hy, t rauma, post coronary art ery cat het erizat ion, encephalit is, AI DS,
cyst icercosis, syphilis, brucellosis, sickle-cell t rait , neurosyphilis, t umor, Arnold-
Chiari malf ormat ion, hydrocephalus, art eriovenous malf ormat ion, met abolic
disorders (e. g. , Fabry's disease, abet alipoprot einemia), syringobulbia, radiat ion
eff ect , PSP, hepat ic encephalopat hy, pernicious anemia, and drugs (phenyt oin,
amit ript yline, phenot hiazines, t ricyclics, propranolol, lit hium, narcot ics,
barbit urat es, and int ravenous FK 506) [133, 220, 417, 465, 480] . Bilat eral I NO
has been described w it h isolat ed t egment al mesencephalic hemorrhage due t o
cocaine abuse [201] . Bilat eral I NO w it h progressive bilat eral visual loss may be
t he f irst sign of a paraneoplast ic encephalomyelit is [620] . Bilat eral damage t o
t he MLF and subsequent lat eral ext ension of damage t o t he region of t he t w o
abducens nerve f asciculi has been described as causing complet e bilat eral
horizont al gaze paralysis in t w o pat ient s w it h mult iple sclerosis [528] .
The pat t ern of ext raocular muscle w eakness w it h myast henia gravis and t he
G uillain-Barré syndrome can mimic I NO as can t hyroid orbit opat hy, orbit al
pseudot umor, part ial oculomot or nerve palsy, Fisher syndrome, penicillamine-
induced pseudo-I NO , myot onic muscular dyst rophy, and surgical paresis of t he
MR muscle [42, 361, 378, 809] . At ypical I NO w it h nyst agmus in t he adducti ng
eye has been described w it h abet alipoprot einemia (vit amin E def iciency) [849] .
The vit amin E def iciency syndrome superf icially resembles t he w all-eyed bilat eral
int ernuclear opht halmoplegia–Wall-Eyed Bilat eral I nt ernuclear O pht halmoplegia
(WEBI NO ) syndrome (see subsequent t ext ) in t hat pat ient s demonst rat e XT
associat ed w it h adduct ion limit at ion and dissociat ed horizont al nyst agmus on
lat eral gaze. How ever, in vit amin E def iciency, saccades are slow er in t he
abduct ing eye, rat her t han t he adduct ing eye, and t he dissociat ed nyst agmus is
of great er amplit ude in t he adduct ing eye [849] . This mot ilit y impairment is
especially not ed w it h abet alipoprot einemia w it h ot her f indings including at axia,
w eakness, post erior column dysf unct ion, and pigment ary ret inopat hy.
I n bilat eral int ernuclear opht halmoplegia, t he eyes are generally aligned in
primary gaze. I nst ances of XT, w it h bot h eyes deviat ed lat erally, have been
t ermed wal l eyed-bi l ateral i nternucl ear ophthal mopl egi a or WEBINO syndrome
[ 230, 242, 390, 743] . This syndrome may occur w it h midbrain lesions involving
bot h MR subnuclei and bot h MLFs, or w it h bilat eral MLF lesions in pat ient s w it h
a previously compensat ed st rabismus (exophoria). Convergence is of t en absent
[ 743] . A unilat eral I NO may also be associat ed w it h XT (wal l -eyed monocul ar
i nternucl ear ophthal mopl egi a–Wal l -Eyed Monocul ar Internucl ear
O phthal mopl egi a or WEMINO syndrome) [357, 386] ; acut ely unilat eral I NO may
be associat ed w it h an esophoria, perhaps due t o increased vergence t one.
Rarely, I NO may be associat ed w it h XT in t he cont ralat eral eye due t o
overact ion of t he cont ralat eral PPRF under f ixat ion w it h t he paret ic eye [441] .
What used t o be called Lutz posteri or i nternucl ear ophthal mopl egi a is now
know n as int ernuclear opht halmoplegia of abduct ion [593, 784] . Abduct ion,
rest rict ed on volit ion, can be f ully eff ect ed by ref lex maneuvers, such as cold
caloric st imulat ion. Unilat eral or bilat eral int ernuclear opht halmoplegia of
abduct ion, occasionally associat ed w it h adduct ion nyst agmus of t he cont ralat eral
eye, has been described w it h ipsilat eral rost ral pont ine or mesencephalic lesions
[ 765] . Abduct ion paresis is at t ribut ed t o impaired inhibit ion of t he t onic rest ing
act ivit y of t he ant agonist ic MR muscle. The prenuclear origin of t he disorder
is based on morphologic and neurophysiologic evidence of an ipsilat eral

inhibit ory connect ion bet w een t he PPRF and t he oculomot or nucleus running
close t o but separat ed f rom t he MLF [765] .
“On e-an d-a-Half” Syn drome

I n t hese cases t here is a conjugat e gaze palsy t o one side (“one”) and impaired
adduct ion on looking t o t he ot her side (“and a half ”) [610, 825] . As a result , t he
only horizont al movement remaining is abduct ion of one eye, w hich exhibit s
nyst agmus in abduct ion. Vert ical movement s and convergence are spared. The
lesion responsible f or t his condit ion involves t he PPRF or abducens nucleus and
t he adjacent MLF on t he side of t he complet e gaze palsy. A clinical dist inct ion
can be made bet w een t he horizont al gaze palsy in lesions aff ect ing t he rost ral
part of t he PPRF and t hose at t he level of t he abducens nucleus [193] . When all
rapid eye movement s (saccades and quick phases of nyst agmus) ipsilat eral t o
t he lesion are abolished w it h preserved ipsilat eral vest ibulo-ocular response, t he
rost ral part of t he PPRF is involved (dissociat ed ipsilat eral horizont al conjugat e
gaze palsy). I n cont rast , lesions at t he low er pont ine level, aff ect ing t he PPRF
and/ or abducens nucleus, are associat ed w it h an ipsilat eral horizont al gaze palsy
and loss of ref lex vest ibular eye movement s (nondissociat ed ipsilat eral horizont al
gaze palsy) [193] . Pat ient s w it h t he one-and-a-half syndrome of t en have XT of
t he eye opposit e t he side of t he lesion (paral yti c ponti ne XT) because t he eyes
t end t o drif t t o t he side opposit e t he lesion due t o t he gaze palsy, but adduct ion
in t his direct ion is limit ed by t he MLF lesion [705] . Rarely, a primary posit ion ET
may occur w it h t he one-and-a-half syndrome, likely due t o involvement of t he
abducens nerve f ascicle superimposed upon a lesion of t he PPRF and MLF
[ 825] .
The one-and-a-half syndrome may be associat ed w it h ocular bobbing [246] and,
more of t en, f acial nerve palsy [ t he “ei ght-and-a-hal f syndrome”) [219] . Pat ient s
w it h one-and-a-half syndrome and f acial nerve palsies may develop oculopalat al
myoclonus w eeks t o years af t er t he onset of t he ocular mot ilit y problem [840,
857] . The one-and-a-half syndrome has also been described w it h f acial diplegia
(t he “15½ syndrome” [ 1½ + 7 +7 = 15½] ) [43] . I t may also be associat ed w it h
supranuclear f acial w eakness on t he same side as t he gaze palsy and
int ernuclear opht halmoplegia w it h lesions of t he paramedian aspect of t he dorsal
pont ine t egment um, providing evidence f or t he exist ence of cort icof ugal f ibers
t hat ext end t o t he f acial nucleus in t he dorsal paramedian pont ine t egment um.
[ 19] .
The one-and-a-half syndrome is most of t en caused by mult iple sclerosis,
inf arct s, hemorrhages, t rauma, basilar art ery aneurysms, brainst em
art eriovenous malf ormat ions, and t umors [426, 586, 825] . A pseudo one-and-a-
half syndrome may be caused by myast henia gravis [55, 184] and t he Miller-
Fisher syndrome [59] .
A somew hat similar syndrome may result f rom t w o separat e lesions involving
bot h MLFs and t he root s of t he abducens nerve on t he side of t he unilat eral
horizont al “gaze” palsy. How ever, in t his case, if t he “gaze” palsy is incomplet e,
t he eyes w ould move disconjugat ely in t he direct ion of t he gaze palsy [610] . A
t rue gaze palsy due t o unilat eral PPRF damage causes concomit ant paresis of
bot h eyes. Also, a unilat eral I NO may be associat ed w it h an ipsilat eral abducens
nerve palsy (f ascicular involvement ) w it hout abducens nuclear or PPRF damage
(i. e. , no associat ed gaze palsy). Anot her t ype of one-and-a-half syndrome has
been described w it h rost ral brainst em inf arct ion. The pat ient developed a lef t
pt osis, right conjugat e gaze palsy, and abduct ion paralysis of lef t eye on
at t empt ed gaze t o lef t w it h adduct ion nyst agmus of right eye. The horizont al eye
movement disorder w as similar t o one-and-a-half syndrome except f or an
abduct ion paralysis and adduct ion nyst agmus. The lef t pt osis and adduct ion
paralysis w ere at t ribut ed t o a lef t oculomot or f ascicular involvement , w hile t he
right -sided ET and abduct ion paresis w ere consist ent w it h pseudoabducens
palsy. Lef t abduct ion paralysis w it h adduct ion nyst agmus on t he right side on
at t empt ed gaze t o lef t w as t hought t o be due t o involvement of t he para-MLF
pat h on t he lef t side and is called i nternucl ear ophthal mopl egi a in abduct ion.
[ 143]
A diff erent one-and-a-half syndrome has been described in a pat ient w it h
mucormycosis of t he cavernous sinus [141] . The pat ient had an ipsilat eral sixt h
nerve palsy due t o cavernous sinus involvement and a cont ralat eral horizont al
gaze palsy due t o simult aneous carot id art ery occlusion w it h inf arct ion of t he
f ront al lobe. Cont rary t o t he pont ine one-and-a-half syndrome, in w hich
abduct ion in one eye is t he preserved horizont al movement , t his pat ient had only
preserved adduct ion in one eye (cont ralat eral t o t he sixt h nerve palsy) [141] .
Vertical Dyscon ju gate Gaze Palsies

Monocul ar el evati on paresi s (“doubl e el evator pal sy”) may occur w it h pret ect al
supranuclear lesions cont ralat eral t o t he paret ic eye or ipsilat eral t o t he paret ic
eye t hat int errupt eff erent s f rom t he rost ral int erst it ial nucleus of t he MLF t o t he
SR and I O subnuclei (of t en Bell's phenomenon is int act ) [349, 763] . Double
elevat or palsy may
simply be an asymmet ric upgaze palsy t hat clinically present s as monocular

elevat ion paresis in t he more severely aff ect ed eye (t hus, not a t rue monocular
elevat or palsy) [763] . I t has also been described w it h paramedial midbrain
inf arct s aff ect ing select ively t he lat eral-most f ibers of t he f ascicular port ion of
t he oculomot or nerve [565] .
A verti cal one-and-a-hal f syndrome, w it h vert ical upgaze palsy and monocular
paresis of dow ngaze on t he side of t he lesion [92, 349, 756 or cont ralat eral t o
t he lesion [349] , has been described w it h t halamo-mesencephalic inf arct ion [92] ,
best explained by select ive damage t o supranuclear pat hw ays or part ial nuclear
involvement [756] . Anot her vert ical one-and-a-half syndrome has been described
consist ing of impairment of all dow nw ard rapid eye movement s (including t he
vest ibulo-ocular ref lex) and dow nw ard smoot h pursuit (nondissociat ed dow ngaze
paralysis) associat ed w it h monocular paralysis of elevat ion [192] . Bell's
phenomenon and all t ypes of horizont al eye movement s w ere preserved. Bilat eral
mesodiencephalic region inf arct ions w ere f ound t hat may have aff ect ed t he
eff erent t ract s of t he riMLF bilat erally and t he premot or f ibers t o t he
cont ralat eral SR subnucleus and ipsilat eral SO subnucleus, eit her bef ore or af t er
t he decussat ion in t he PC [192] . The unusual combinat ion of loss of depression
in one eye and of elevat ion in t he ot her occurred in a pat ient w it h a vascular
malf ormat ion in t he rost ral midbrain. This abnormalit y w as t hought t o be due t o
int errupt ion of supranuclear pat hw ays f or vert ical gaze and not due t o a
subnuclear lesion of oculomot or nerve nuclear complex [671] . I n anot her pat ient ,
monocular elevat ion paresis of t he right eye w as associat ed w it h cont ralat eral
paresis of dow nw ard gaze, and subt le bilat eral pt osis. MRI disclosed a unilat eral
embolic inf arct ion rest rict ed t o t he mesodiencephalic junct ion involving t he lef t
paramedian t halamus. Preserved vert ical oculocephalic movement s and int act
Bell's phenomenon suggest ed a supranuclear lesion. This rare “crossed vert ical
gaze paresis” result ed f rom a lesion near t he oculomot or nucleus aff ect ing
ipsilat eral dow nw ard gaze and cont ralat eral upw ard gaze f ibers, originat ing in
t he riMLF [832] . A coexist ing vert ical and horizont al one-and-a-half syndrome has
been described w it h an inf arct involving t he right medial t halamus, lef t dorsal
upper midbrain, and lef t cerebellum [758] . O nly t he right eye could abduct w it h
monocular horizont al nyst agmus, and only t he lef t eye could gaze dow n.
Skew Deviation
Alt hough vert ical misalignment of t he eyes may be caused by lesions of t he
ocular mot or nerves or muscles (e. g. , w it h myast henia gravis), t he t erm skew
devi ati on is reserved f or vert ical misalignment result ing f rom supranuclear
derangement s. The angle bet w een t he axes of t he eyes may or may not be
const ant in various gaze posit ions but skew deviat ion is not associat ed w it h t he
presence of a primary and secondary deviat ion. Unlike t he ot her causes of
acquired vert ical st rabismus (e. g. , SO palsy, t hyroid opht halmopat hy, myast henia
gravis, et c. ), t he eyes usually are not rot at ed in skew deviat ion [787] . Absence
of rot at ion or cyclodeviat ion is best t est ed by Maddox rods of diff erent colors
over each eye. Wit h skew deviat ion, t he Bielschow sky head-t ilt t est (see
preceding t ext ) is of t en negat ive. How ever, cyclodeviat ion may also occur w it h
skew deviat ion (see subsequent t ext ) [268] . Skew deviat ion occurs w henever
peripheral or cent ral lesions cause an imbalance of ot olit h input s and can
accompany lesions at diff erent areas of t he brainst em (mesencephalon t o
medulla) or cerebellum [554, 748, 842] . O ccasionally, increased int racranial
pressure, Fisher syndrome [225] , or hepat ic coma may cause skew deviat ion.
When skew deviat ion varies in diff erent gaze posit ions, it usually indicat es a
medullary lesion. Peripheral vest ibular disease can cause cont ralat eral
hypert ropia, in w hich t he cont ralat eral eye is higher t han t he ipsilat eral eye.
Lat eral pont omedullary lesions aff ect ing t he VN may result in skew deviat ion w it h
t he low er eye on t he side of t he lesion. By cont rast , t he eye on t he side of a
unilat eral MLF lesion t ends t o be higher.
Lesions near t he PC occasionally are manif est w it h a skew deviat ion, in w hich
t he ipsilat eral eye is higher, or t here is sl owl y al ternati ng skew devi ati on, in
w hich one eye f alls as t he ot her rises [170] . This change of posit ion t akes f rom
10 t o 30 seconds w it h t he new posit ion maint ained f or 30 t o 60 seconds.
Alt ernat ing skew deviat ion (incomit ant skew ) in w hich t he hypert ropia alt ernat ed
on gaze t o eit her side has been described associat ed w it h pret ect al lesions
including acut e hydrocephalus, t umor, st roke, mult iple sclerosis, t rauma, lit hium
exposure, Wernicke's encephalopat hy, t ent orial herniat ion, and spinocerebellar
degenerat ions [404] . Pat ient s w it h bilat eral adduct ing hypot ropia (alt ernat ing
skew on lat eral gaze) w it h accompanying pret ect al signs (e. g. , upw ard gaze
palsy, def ect ive pupillary react ion, and nyst agmus) may need urgent surgical
int ervent ion [13] . By cont rast , alt ernat ing skew on lat eral gaze (bilat eral
abduct ing hypert ropia) w it h DBN and at axia has been not ed w it h lesions of
cerebellum or of t he cervicomedullary junct ion [321, 554] .
Skew deviat ion may be const ant or t ransient ; periodic or t ransient vert ical
divergence may occur w it h migraine or vert ebrobasilar ischemia. Paroxysmal
skew deviat ion has been described as a present ing sign of a unilat eral
ast rocyt oma [17] . Recurrent at t acks (last ing 20 t o 80 seconds) of cont ract ion of
t he lef t f ront alis muscle accompanied by skew deviat ion and t orsional nyst agmus
have been ascribed t o t ransient ischemia causing paroxysmal discharges of
neurons of t he vest ibulo-ocular syst em and f acial mot or pat hw ays [740] .
Epilept ic skew deviat ion has also been described [270] . Paroxysmal alt ernat ing
skew deviat ion and direct ion-changing nyst agmus has been not ed af t er part ial
dest ruct ion of t he uvula of t he cerebellum [633] . The eye movement disorder w as
t hought t o result f rom a lesion of t he lef t VN, causing right over lef t skew and
right beat ing rest ing nyst agmus, and a disrupt ion of cerebellar inhibit ion of VN,
causing alt ernat ing act ivit y in t he vest ibular syst em w it h int ermit t ent reversal of
t he skew deviat ion and paroxysmal nyst agmus t ow ards t he side of t he lesion.
A pat ient w it h locked-in syndrome due t o pont ine inf arct ion had dysconjugat e
vert ical and t orsional ocular movement s [600] . When t he pat ient w as asked t o
look t o t he right , t he right eye moved upw ard w it h int orsion and t he lef t eye
moved dow nw ard w it h ext orsion. When t he pat ient w as asked t o look t o t he lef t ,
t he reversal cycle, w it h t he lef t eye moving upw ard w it h int orsion and t he right
eye moving dow nw ard w it h ext orsion, w as observed. Horizont al gaze w as limit ed
t o minimal movement . I t w as t hought t hat t his int ermit t ent dysconjugat e
abnormalit y w as mediat ed by t he I NC.
I n some pat ient s, skew deviat ion may be associat ed w it h ocular t orsion and head
t ilt (t he ocul ar ti l t reacti on [ O TR]) [314] . I n t he O TR, t he head t ilt , conjugat e eye
t orsion, and hypot ropia are all t o t he same side suggest ing t hat t his react ion is a
mot or compensat ion of a lesion-induced apparent eye-head t ilt ; t he cont ralat eral
head t ilt represent s a compensat ory response t o t he perceived t ilt of t he
subject ive visual vert ical–Subject ive Visual Vert ical (SVV) [106] . O t olit h input s t o
t he I NC f rom t he cont ralat eral vest ibular (especially lat eral vest ibular) nucleus
and mot or out put s f rom t he I NC t o cervical and ocular mot oneurons are likely
involved [314] . A lef t O TR could be due t o a lesion of t he lef t labyrint h, lef t
vest ibular nerve, lef t vest ibular nucleus (e. g. , Wallenberg syndrome), or right
mesodiencephalon [24, 111, 314, 412, 583, 651, 816 suggest ing t he exist ence of
a crossed gravicept ive pat hw ay (possibly t he MLF) bet w een t he vest ibular
nucleus and t he cont ralat eral I NC [314] . Theref ore, cases of O TR have been
report ed in vest ibular nerve injury, audit ory t rauma, Wallenberg syndrome, lat eral
medullary compression, pont omedullary ischemia, and mesodiencephalic lesions
[ 104, 111, 204, 314, 412, 504, 634, 651] . The vert ical diplopia and cyclot orsion
occasionally not ed in cases of vest ibular neuronit is is likely a f orm of skew
deviat ion t hat occurs as part of t he O TR f rom a peripheral vest ibular lesion
[ 676] . The absence of brainst em signs in peripheral O TR helps t o exclude a
cent ral cause f or t he vert ical diplopia. The O TR may be toni c (i. e. , persist ent ) or
phasi c (i. e. , paroxysmal), t he lat t er likely due t o increased I NC neuron act ivit y
(e. g. , disinhibit ion) [314, 340] .
Tw o t ypes of O TR have been described [108] : (a) an ascending pont omedullary
vest ibulo-ocular (VO R)-O TR w it h ipsilat eral lesions of t he vest ibulo-ocular
pat hw ay in t he roll plane f rom t he labyrint h t o t he VN; t his t ype is charact erized
by dysconjugat e ocular t orsion and occurs if t he ant erior, post erior, or bot h SCC
or ot olit h pat hw ays are aff ect ed. I t simply ref lect s t one imbalance of t he VO R;
and (b) a descending mesencephalic int egrat or–O TR w it h cont ralat eral lesions of
t he rost ral midbrain int egrat or cent er f or eye–head coordinat ion in t he roll plane.
This t ype is charact erized by conjugat e ocular t orsion.
Skew deviat ion associat ed w it h concomit ant ocular t orsion and t ilt s of t he SVV
t ow ard t he undermost eye is a sensit ive brainst em sign of localizing and
lat eralizing value. I n a st udy of pat ient s w it h unilat eral brainst em inf arct s
present ing w it h skew deviat ion and ocular t orsion, all skew deviat ions w ere
ipsiversive (ipsilat eral eye w as undermost ) w it h caudal pont omedullary lesions
and cont raversive (cont ralat eral eye w as low ermost ) w it h rost ral
pont omesencephalic lesions [105] . The ocular skew t orsion sign indicat es a
vest ibular t one imbalance in t he roll plane secondary t o gravicept ive pat hw ay
lesions [105] .
A pat ient w it h a dorsal midbrain syndrome w it h an ipsilat eral skew deviat ion has
been described due t o a right paramedian t halamic inf arct t hat perhaps impaired
t he t onic input of t he t halamus on t he int egrat or cent er [20] . Several pat ient s
have been described w it h t onic cont raversive part ial O TRs due t o unilat eral
caudal cerebellar lesions. The pat ient s had t onic cont raversive conjugat e ocular
t orsion. Theref ore, t he O TR, a brainst em ot olit h-ocular ref lex of probable
ut ricular origin, is under t he inhibit ory cont rol of t he ipsilat eral caudal
cerebellum, possibly t he nodulus. This t onic cont raversive O TR w it h unilat eral
cerebellar lesion is probably caused by an increased t onic rest ing act ivit y in t he
ipsilesional vest ibular nucleus due t o a loss of inhibit ion f rom t he lesioned
nodulus [534] . A pat ient w it h a
cerebellar inf arct can, t heref ore, present w it h imbalance as t he only neurologic
sympt om and w it h conjugat e ocular t orsion as t he only specif ic neurologic sign
[ 534, 551] .
Skew deviat ion associat ed w it h concomit ant ocular t orsion and t ilt s of t he SVV
t ow ard t he undermost eye is a sensit ive brainst em sign of localizing and
lat eralizing value. The topographi c di agnosi s of vesti bul ar syndromes i n the rol l
pl ane may be summarized as f ollow s [106, 107] :
1. The f undament al pat t ern of eye–head t ilt in roll, eit her complet e O TR or
skew t orsion w it hout head t ilt , indicat es a unilat eral peripheral def icit of
ot olit h input or a unilat eral lesion of gravicept ive brainst em pat hw ays f rom
t he VN (crossing midline at low er pont ine level) t o t he I NC in t he rost ral
midbrain.
2. Skew deviat ion and t ilt s of t he perceived visual vert ical occur w it h peripheral
or cent ral vest ibular lesions f rom t he labyrint h t o t he visual cort ex and
represent t he most sensit ive sign of vest ibular t one imbalance in roll.
3. All t ilt eff ect s, percept ual, ocular mot or, and post ural, are ipsiversive
(ipsilat eral eye low ermost ) w it h unilat eral peripheral or pont omedullary
lesions below t he crossing of t he gravicept ive pat hw ays. They indicat e
involvement of medial and/ or superior VN, mainly supplied by t he vert ebral
art ery.
4. All t ilt eff ect s in unilat eral pont omesencephalic brainst em lesions are
cont raversive (cont ralat eral eye low ermost ) and indicat e involvement of t he
MLF (paramedian art eries arising f rom t he basilar art ery) or I NC and riMLF
(paramedian superior mesencephalic art eries arising f rom t he basilar art ery).
5. Unilat eral lesions of vest ibular st ruct ures rost ral t o t he I NC t ypically manif est
w it h deviat ions of perceived vert ical w it hout concurrent eye–head t ilt .
6. O TR in unilat eral paramedian t halamic inf arct ion (paramedian t halamic
art eries f rom basilar art ery) indicat es simult aneous ischemia of t he
paramedian rost ral midbrain including t he I NC.
7. Unilat eral lesions of t he post erolat eral t halamus can cause t halamic ast asia
and moderat e ipsiversive or cont raversive skew deviat ion and t ilt s of t he
perceived visual vert ical, t hereby indicat ing involvement of t he “vest ibular”
t halamic subnuclei (t halamogeniculat e art eries).
8. Unilat eral lesions of t he pariet oinsular vest ibular cort ex cause moderat e,
most ly cont raversive skew deviat ion and t ilt s of t he perceived visual vert ical
(t emporal branches of t he middle cerebral art ery or deep perf orat ors).
9. A skew deviat ion and t ilt s of t he perceived visual vert ical f ound w it h
monocular but not w it h binocular view ing is t ypical of a t rochlear or
oculomot or palsy rat her t han a supranuclear gravicept ive brainst em lesion.
I nf arct ion in t he dist ribut ion of t he middle cerebral art ery, especially aff ect ing
t he post erior insula, may cause cont raversive, pat hologic SVV t ilt s [109] . The
pariet oinsular vest ibular cort ex t heref ore likely represent s t he int egrat ion cent er
of t he mult isensory vest ibular cort ex areas w it hin t he pariet al lobe.
Nystagmus and Other Ocular Oscillations

Nyst agmus may be def ined as a biphasic ocular oscillat ion cont aining slow eye
movement s t hat are responsible f or it s genesis and cont inuat ion. Fine nyst agmus
t hat may not be not iced by simple inspect ion of t he eyes may be det ect ed on
f unduscopic examinat ion. I t is import ant t o t ake int o account t hat t he direct ion in
w hich t he ret inal vessels can be seen t o oscillat e is opposit e t he direct ion in
w hich t he globe oscillat es. Changes in t he amplit ude of nyst agmus w hen t he
pat ient f ixat es on an object serve t o separat e some variet ies of nyst agmus.
Theref ore, nyst agmus should be observed during f ixat ion and af t er removing
f ixat ion by having t he pat ient w ear Frenzel lenses or by recording eye
movement s in t he dark. A simple maneuver is t o observe t he rat e and amplit ude
of t he nyst agmus on f unduscopic examinat ion w it h a handheld opht halmoscope
w hile t he pat ient f ixat es w it h t he ot her eye. Then, as t he light s of t he examining
room are t urned off , t hereby removing f ixat ion, any changes in nyst agmus are
not iced.
The t o-and-f ro ocular movement t hat t akes place as an individual w at ches t he
t ree line w hen driving alongside a f orest w as described in t he preceding t ext as
opt okinet ic nyst agmus. This t ype of jerk nystagmus, w it h a slow drif t and a quick
correct ive component , is more common t han pendul ar nystagmus, in w hich t he
eyes move w it h t he same speed in bot h direct ions.
Oscillopsia
O scillopsia is an illusory percept ion of environment al movement and may assume
f our f orms [128] : (a) associat ed w it h acquired jerk nyst agmus (t he environment
moves in t he direct ion opposit e t he slow phase of t he nyst agmus; no movement
is perceived during t he f ast phase due t o visual t hreshold elevat ion), (b)
associat ed w it h pendular nyst agmus (perceived as a
t o-and-f ro movement ), (c) associat ed w it h SO M (jelly-like quivering), and (d)

associat ed w it h bilat eral labyrint hine dysf unct ion (cont inuous environment al
jumping, e. g. , w it h t he heart beat ). O f t en oscillopsia is increased by t he
movement of t he head, as w hen w alking, and t hen it is relat ed t o impairment of
t he vest ibular syst em, w hich st abilizes images in t he ret ina. O scillopsia in t he
vert ical plane may result f rom bilat eral MLF involvement . Condit ions t hat may
cause oscillopsia even w hen t he head remains st ill include acquired pendular
nyst agmus, paresis of an ext raocular muscle, and epilepsy.
Optokinetic Drum
A handheld opt okinet ic drum or t ape does not t est t he opt okinet ic syst em but is
usef ul in t est ing pursuit and saccades. When t he drum is rot at ed t o t he pat ient 's
right , a right w ard slow phase (pursuit ) is f ollow ed by a compensat ory quick
phase (saccade) t o t he lef t . Theref ore, t he drum or t ape is usef ul in t he f ollow ing
sit uat ions [182] :
1. Asymmet ry of t he slow phase may be seen w it h hemispheral, especially

pariet al, lesions.
2. Early saccade impairment may be evident in PSP, Hunt ingt on's disease,
olivopont ocerebellar at rophy, congenit al ocular mot or apraxia, and sea-blue
hist iocyt osis.
3. I nt ernuclear opht halmoplegia may be more clearly def ined.
4. Vert ical rot at ion may bring out ret ract ion nyst agmus.
5. Hyst eria or malingering may be support ed because a pat ient cannot f ollow
t he t ape or drum unless visual f unct ion is present .
6. Wit h congenit al nyst agmus, reversal of opt okinet ic nyst agmus may occur
Nyst agmus induced by opt okinet ic or vest ibular st imuli is physiologic. Nyst agmus
in ext reme lat eral or vert ical gaze (end-point nyst agmus) can also be f ound in
normal persons. I t t ends t o w ane easily and belongs t o t he variet y described in
t he subsequent t ext as “gaze-evoked” nyst agmus. The f ollow ing paragraphs deal
primarily w it h t he localizing value of t he pat hologic variet ies of nyst agmus.
Jerk Nystagmus
Nyst agmus is generally named according t o t he direct ion of t he f ast , correct ive
component . Theref ore, horizont al nyst agmus t o t he lef t implies t hat t he eyes
t end t o drif t slow ly t o t he right , correct ed by quick saccades t o t he lef t t hat
bring t he eyes back t o w here t he pat ient w ishes t o look. Analysis of t he slow
component proves most helpf ul f or t he anat omic diagnosis of nyst agmus. The
slow component may have a unif orm velocit y or may reduce or gain speed as t he
eyes move in t he direct ion of t he slow component .
Systems Classification of Nystagmus
Alt hough t he velocit y charact erist ics of nyst agmus cannot be appreciat ed w it h
t he naked eye, t he easy availabilit y of elect rooculography makes it advisable t o
f ollow t his classif icat ion. Pat hologic nyst agmus may be due t o disorders of t he
vest ibular, gaze-holding, and visual st abilizat ion and pursuit mechanisms.
Vestibular Nystagmus
Vest ibular t one imbalance result s in an asymmet ric input t o t he horizont al gaze
generat or; vest ibular nyst agmus alw ays show s linear (st raight -line) slow phases
ref lect ing a persist ent drive of t he eyes t ow ard t he damaged vest ibular
apparat us (labyrint h, nerve, nuclei). The slow phases of t his nyst agmus are
decreased by f ixat ion and increased in darkness, w it h eye closure, or w it h t he
use of Frenzel lenses. Fixat ion inhibit ion of nyst agmus may be relat ed t o an
opposing smoot h pursuit f orce and requires t he int egrit y of t he cerebellar
f locculus. Theref ore, nyst agmus present during at t empt ed visual f ixat ion of t en
ref lect s bot h t he underlying dist urbance creat ing t he nyst agmus and t he impaired
smoot h pursuit t hat f ails t o dampen t he slow drif t .
Gaze-Holding Nystagmus
An impaired neural i ntegrator (“leaky” int egrat or) may cause gaze-evoked
nyst agmus w it h a negat ive exponent ial slow phase. The velocit y of t he slow
component decreases as t he eyes move f rom t he periphery of t he orbit , w here
t he pull due t o t he viscosit y of t he orbit al t issues is great est , t ow ard rest ing in
primary posit ion. The inabilit y of t he gaze-holding mechanisms t o keep t he eyes
eccent ric in t he orbit is of t en present w it h cent ral or peripheral lesions causing
w eakness of eye movement s. For t his reason, t his t ype of nyst agmus is of t en
ref erred t o as “gaze-pareti c” nystagmus.
Visual Stabilization Nystagmus

Hi gh-gai n i nstabi l i ty of slow eye movement subsyst ems (e. g. , t he pursui t
syst em) may also cause nyst agmus, w it h t he nyst agmus slow phase having an
exponent ially increasing t ime course
(“runaw ay” movement s). Such nyst agmus in t he horizont al plane is seen in
congenit al nyst agmus and in t he vert ical plane is seen w it h cerebellar disease.
High-gain inst abilit y may also result in congenit al or acquired pendular
nyst agmus.
Clinical Classification of Nystagmus

I n assessing a pat ient w it h abnormal eye oscillat ions, it is f irst usef ul t o not e
w het her t he oscillat ions are conf ined t o one eye (monocular), involve mainly one
eye (binocular asymmet ric or dissociat ed), or involve bot h eyes symmet rically
(binocular symmet ric) [128] .
M onocular Eye Oscillations and Asymmetric Binocular

Eye Oscillations
Monocul ar eye osci l l ati ons and asymmetri c bi nocul ar eye osci l l ati ons may be
due t o spasmus nut ans and it s mimickers, monocular visual deprivat ion or loss,
monocular pendular nyst agmus, int ernuclear opht halmoplegia and it s mimickers,
part ial paresis of ext raocular muscles, rest rict ive syndromes of ext raocular
muscles, or SO M.
Spasmus nutans is a benign syndrome charact erized by a t riad of head nodding,
nyst agmus, and abnormal head post ure [295, 857] . This condit ion usually has it s
onset in t he f irst year of lif e and remit s spont aneously w it hin one mont h t o
several years (up t o 8 years) of onset . The sinusoidal nyst agmus is of t en
int ermit t ent , asymmet ric or unilat eral, and of high f requency and small amplit ude
w it h a “shimmering” qualit y. The nyst agmus is usually horizont al but may have a
vert ical or t orsional component . The irregular head nodding w it h spasmus nut ans
has horizont al, vert ical, or mixed component s. Pat ient s of t en also demonst rat e a
head t urn or t ilt . I n all children w it h spasmus nut ans, monocular nyst agmus, or
asymmet ric pendular nyst agmus, one must consider t hat t he nyst agmus may be
due t o t umor of t he opt ic nerve, chiasm, t hird vent ricle, or t halamus [26, 229,
570, 723] . These lat t er pat ient s may also have visual loss, opt ic at rophy, or
ot her signs of t umor [434] . A myopic child suspect ed of having spasmus nut ans
should also undergo elect roret inographic t est ing t o exclude t he diagnosis of
congenit al st at ionary night blindness [455] .
Monocular nyst agmus may occur in adult s or children w it h acqui red monocul ar
vi sual l oss and consist s of small, slow vert ical pendular oscillat ions in t he
primary posit ion of gaze. I t may develop years af t er uniocular visual loss
(Hei mann-Bi el schowsky phenomenon) and may improve if vision is correct ed
[ 626, 723, 851] . Monocular, small amplit ude, f ast f requency, and predominant ly
horizont al nyst agmus in children may be caused by unilat eral ant erior visual
pat hw ay disease [293] .
Epi l epti c monocul ar hori zontal nystagmus has been described in a cognit ively
int act adult w it h normal vision [296] . Focal seizures originat ed in t he occipit al
lobe cont ralat eral t o t he involved eye, and an associat ed st ruct ural lesion w as
t hought t o represent a f orme f rust e of t he St urge-Weber syndrome. I t w as
hypot hesized t hat t he seizure discharge eit her act ivat ed a cort ical saccade
region and caused simult aneous supranuclear inhibit ion of ipsilat eral eye
movement or t riggered monocular eye movement commands.
Acqui red monocul ar pendul ar nystagmus may also occur w it h mult iple sclerosis,
neurosyphilis, and brainst em inf arct (t halamus and upper midbrain) and may be
vert ical, horizont al, or mult ivect orial [626] . Monocular DBN may occur w it h acut e
inf arct ion of t he medial t halamus and upper midbrain and w it h pont ocerebellar
degenerat ion; t his abnormalit y is likely due t o dysf unct ion of t he ipsilat eral
brachium conjunct ivum [93, 373] . Cont ralat eral unilat eral DBN has been
described w it h a paramedian t halamopeduncular inf arct ion [591] . Monocular
rot at ory nyst agmus may occur w it h brainst em lesions [399] . O ne pat ient has
been described w ho developed ict al monocular horizont al nyst agmus during a
generalized seizure t riggered by phot ic st imulat ion [374] .
Nyst agmus is seen only in t he abduct ing eye in I NO and in pseudo-I NO
syndromes (see preceding t ext ). SO M (described earlier) may also cause
vert ical oscillopsia, vert ical or t orsional diplopia, or bot h.
Dysconjugate Bilateral Symmetric Eye Oscillations

I f t he ocular oscillat ions involve bot h eyes t o a relat ively equal degree, t he next
st ep in evaluat ion involves det ermining w het her t he eye movement s are
disconjugat e (t he eyes moving in opposit e direct ions) or conjugat e (bot h eyes
moving in t he same direct ion) [128] . When t he oscillat ions are disconjugat e, t he
examiner should det ermine w het her t he oscillat ions are vert ical or horizont al.
Verti cal di sconjugate eye osci l l ati ons are usually due t o see-saw nyst agmus.
Hori zontal di sconjugate eye osci l l ati ons include convergence-ret ract ion
nyst agmus (nyst agmus ret ract orius), divergence nyst agmus, repet it ive
divergence, and oculomast icat ory myorhyt hmia.
See-saw Nystagmus
See-saw nystagmus ref ers t o a cyclic movement of t he eyes w it h a conjugat e
t orsional component and a disjunct ive vert ical component : w hile one eye rises
and int ort s, t he ot her f alls and ext ort s; t he vert ical and t orsional movement s are
t hen reversed, complet ing t he cycle [564] . This nyst agmus is usually pendular,
but see-saw jerk nyst agmus has been described w it h brainst em lesions aff ect ing
t he mesodiencephalon or lat eral medulla [188, 313, 317] . I n some pat ient s, one
half -cycle of see-saw nyst agmus alt ernat es w it h opposit ely direct ed quick
phases (hemi -see-saw nystagmus) [ 315] .
Et iologies of see-saw nyst agmus are out lined in Table 8-10. Lesions responsible
f or see-saw nyst agmus include large, ext rinsic suprasellar lesions t hat compress
t he mesodiencephalon bilat erally (e. g. , parasellar t umors) or f ocal
mesodiencephalic or lat eral medullary brainst em lesions (e. g. , inf arct ion). I f a
pat ient w it h pendul ar see-saw nyst agmus has a f ocal lesion, t hen t he lesion is
usually a large, ext ensive, suprasellar lesion compressing or invading t he
brainst em bilat erally at t he mesodiencephalic junct ion. Pendular see-saw
nyst agmus may also be congenit al [516] . I f , on t he ot her hand, t he see-saw
nyst agmus has an underlying jerk w avef orm, t hen t he pat ient w ill have an
int rinsic f ocal brainst em lesion, eit her in t he lat eral medulla (usually on t he side
opposit e t he t orsional quick phases) or in t he mesodiencephalon on t he same
side as t he quick phases [314, 317] . See-saw nyst agmus likely represent s
sinusoidal oscillat ions involving cent ral ot olit h connect ions, especially t he I NC
[ 315, 317, 393] . Discret e I NC lesions may cause see-saw or hemi-see-saw
nyst agmus. See-saw nyst agmus may also be part ly due t o an unst able
visuovest ibular int eract ion cont rol syst em. Lesions in t he opt ic pat hw ays may
prevent ret inal error signals, essent ial f or vest ibulo-ocular ref lex adapt at ion,
f rom reaching t he cerebellar f locculus and inf erior olivary nucleus, t hereby
making t he syst em less st able [564] .
Besides t umor and inf arct ion, disease processes causing see-saw nyst agmus
include syringomyelia and syringobulbia, brainst em or t halamic vascular disease,
mult iple sclerosis, t rauma, hydrocephalus, albinism, sept o-opt ic dysplasia,
Leigh's disease, ret init is pigment osa, Arnold-Chiari t ype 1 malf ormat ion,
paraneoplast ic encephalit is w it h t est icular cancer and ant i-Ta ant ibodies, and
w hole brain irradiat ion w it h int rat hecal met hot rexat e [77, 465] . Congenit al see-
saw nyst agmus may lack t he t orsional component or even present w it h an
opposit e pat t ern (i. e. , ext orsion w it h eye elevat ion and int orsion w it h eye
depression) [180] . Wit h congenit al cases, t he binocular t orsional eye movement s
may be in phase w it h clinically visible head oscillat ions (i. e. , head movement s
are not compensat ory f or t he t orsional eye movement s) [636] .
TABLE 8-10 Etiologies of See-Saw Nystagmus
Parasellar masses
Brainstem and thalamic stroke
Multiple sclerosis
Trauma
Arnold-Chiari malformation
Hydrocephalus
Syringobulbia
Paraneoplastic encephalitis (with testicular cancer
and anti-Ta antibodies)
W hole brain irradiation and intrathecal methotrexate
Septo-optic dysplasia, retinitis pigmentosa, and
cone degeneration
Congenital see-saw nystagmusa
a Congenital see-saw nystagmus may lack the torsional
component or even present with an opposite pattern,

that is, extorsion with eye elevation and intorsion with
eye depression. W ith congenital cases, the binocular
torsional eye movements may be in phase with
clinically visible head oscillations (i.e., head
movements are not compensatory for the torsional eye
movements).
Choi et al. report ed a 20-year-old man w it h bilat eral medial medullary inf arct ion
w ho show ed t ransit ion of bow t ie and UBN int o hemi-seesaw nyst agmus [149] .
The f ollow -up MRI revealed near complet e resolut ion of t he right medullary
lesion. This t ransit ion of nyst agmus suggest s t hat t he UBN w as generat ed by
bilat eral lesions in t he ascending pat hw ays f rom bot h ant erior SCCs, and t hat
t he hemi-seesaw nyst agmus w as caused by damage t o t he pat hw ay f rom t he lef t
ant erior SCC.
Horizontal Dysconjugate Eye Oscillations

Convergence may evoke various f orms of nyst agmus (i. e. , convergence-evoked
nyst agmus—see subsequent t ext ). Convergence-retracti on nystagmus is a
disorder of ocular mot ilit y in w hich repet it ive adduct ing saccades, w hich are
of t en accompanied by ret ract ion of t he eyes int o t he orbit , occur spont aneously
or on at t empt ed upgaze [596] . Sliding an opt okinet ic t ape dow nw ard in f ront of
t he pat ient 's eyes may also elicit convergence-ret ract ion nyst agmus.
Convergence-ret ract ion nyst agmus is primarily a saccadic disorder as t he
convergence movement s are not normal vergence movement s but asynchronous,

adduct ing saccades. Mesencephalic lesions aff ect ing t he pret ect al region are
most likely t o cause t his t ype of nyst agmus t hat is of t en associat ed w it h
abnormalit ies of vert ical gaze. The localizat ion of t hese vert ical gaze
abnormalit ies and convergence-ret ract ion nyst agmus w as discussed in t he
preceding t ext . O ccasionally, periodic lat eralized epilept if orm discharges–
Periodic Lat eralized Epilept if orm Discharges (PLEDs) during
elect roencephalography have been f ound t o occur in synchrony w it h ret ract ion
nyst agmus [855] . Convergence nyst agmus has been described w it hout vert ical
gaze abnormalit ies in pat ient s w it h dorsal midbrain st roke and in pat ient s w it h
Arnold-Chiari malf ormat ion [550, 693] . Whipple's disease may also cause
convergence nyst agmus at approximat ely one Hz (pendular vergence oscillat ions)
[ 699] . Convergence nyst agmus has been described in a pat ient w it h spasmus
nut ans [513] .
Di vergence nystagmus (w it h divergent quick phases) may occur w it h hindbrain
abnormalit ies (e. g. , Chiari malf ormat ion) and is associat ed w it h DBN [851] .
These pat ient s have slow phases direct ed upw ard and inw ard. Repeti ti ve
di vergence consist s of a slow divergent movement f ollow ed by a rapid ret urn t o
t he primary posit ion at regular int ervals [576] . This rare disorder has been
described w it h coma f rom hepat ic encephalopat hy. A similar disorder, probably
relat ed t o seizures, w as report ed in a neonat e in associat ion w it h burst -
suppression pat t erns of t he elect roencephalogram [568] .
O cul omasti catory myorhythmi a ref ers t o acquired pendular vergence oscillat ions
of t he eyes associat ed w it h concurrent cont ract ion of t he mast icat ory muscles
[ 6, 337, 501, 696] . When t he myorhyt hmia also involves nonf acial skelet al
muscles, it is called ocul o-f aci al -skel etal myorhythmi a. There is a smoot h,
rhyt hmic eye convergence, w hich cycles at a f requency of approximat ely 1 Hz,
f ollow ed by divergence back t o t he primary posit ion. Rhyt hmic elevat ion and
depression of t he mandible is synchronous w it h t he ocular oscillat ions t hat
persist in sleep and are unalt ered by st imuli. The mast icat ory involvement may
occasionally consist of a permanent bruxism leading t o severe t oot h abrasions
[ 783] . Pat ient s w it h oculomast icat ory myorhyt hmia may also have paralysis of
vert ical gaze, progressive somnolence, and int ellect ual det eriorat ion. This
dist inct movement disorder has been recognized only in Whipple's disease.
Whipple's disease may also cause convergence nyst agmus at approximat ely 1 Hz
(pendular vergence oscillat ions) [699] .
Binocular Symmetric Conjugate Eye Oscillations

Binocular symmet ric conjugat e eye oscillat ions may be divided int o pendular
nyst agmus, jerk nyst agmus, and saccadic int rusions [128] .
Binocular Symmetric Pendular Conjugate Eye

Oscillations
Bi nocul ar symmetri c pendul ar conjugate eye osci l l ati ons may be due t o
congenit al nyst agmus, pendular nyst agmus, oculopalat al myoclonus, spasmus
nut ans (discussed in t he preceding t ext ), and visual deprivat ion nyst agmus.
Congeni tal nystagmus may be not ed at birt h or in early inf ancy, or may emerge
or enhance in t eenage or adult lif e, of t en w it hout apparent provocat ion [195,
299] . I t is seldom f amilial and most of t en idiopat hic. Met abolic derangement s
and st ruct ural anomalies of t he brain, including abnormalit ies of t he eye or
ant erior visual pat hw ays, have been occasionally responsible. More import ant ,
w hen it is f ound lat er in lif e it must be dist inguished f rom ot her f orms of
nyst agmus t hat have a pot ent ially t reat able cause. Congenit al nyst agmus may be
w holly pendular or have bot h pendular and jerk component s. Congenit al jerk
nyst agmus has a slow phase w it h a velocit y t hat increases exponent ially as t he
eyes move in t he direct ion of t he slow phase. O ccasionally, congenit al
nyst agmus may be purely vert ical or t orsional. Alt hough irregular, congenit al
nyst agmus is generally conjugat e and horizont al, even on upgaze or dow ngaze
(uniplanar); visual f ixat ion accent uat es it and act ive eyelid closure or
convergence at t enuat es it [299] . The nyst agmus decreases in an eye posit ion
(“null region”) t hat is specif ic f or each pat ient . Despit e t he const ant eye mot ion,
t hese pat ient s do not experience oscillopsia. When t hey are t est ed w it h a
handheld opt okinet ic t ape or drum, t he quick phase of t he elicit ed nyst agmus
generally f ollow s t he direct ion of t he t ape (reversed optoki neti c nystagmus)
[ 316] .
The cause of congenit al nyst agmus is unknow n but it has been associat ed w it h
many disease processes aff ect ing t he visual aff erent syst em including ocular and
oculocut aneous albinism, achromat opsia, opt ic nerve hypoplasia, Leber's
amaurosis, coloboma, aniridia, cone dyst rophies, corect opia, congenit al
st at ionary night blindness, Chédiak-Higashi syndrome, Joubert 's syndrome, and
peroxisomal disorders [465] . I t has also been associat ed w it h hypot hyroidism
[ 632] .
Latent nystagmus is common and generally congenit al [194, 301, 870] . I t
appears w hen one eye is covered. Bot h eyes t hen develop conjugat e jerk
nyst agmus, w it h t he view ing eye having a slow phase direct ed t ow ard t he nose
(i. e. , t he quick phase of bot h eyes beat t ow ard t he side of t he f ixat ing eye).
Alt hough present at birt h, lat ent nyst agmus is of t en not recognized unt il lat er in
lif e, w hen an at t empt is made t o det ermine monocular visual acuit y during vision
screening at school. Lat ent nyst agmus is usually associat ed w it h st rabismus,
especially ET; amblyopia may occur, and binocular vision w it h normal st ereopsis
is rare. I n addit ion t o horizont al st rabismus, upw ard deviat ion of t he covered eye
(dissociat ed vert ical deviat ion or alt ernat ing sursumduct ion) and a t orsional,
occasionally pendular, component t o t he nyst agmus may occur [158] . Lat ent
nyst agmus is a marker f or congenit al ocular mot or dist urbance and does not
indicat e progressive st ruct ural brain disease [128] .
Mani f est l atent nystagmus is an oscillat ion t hat occurs in pat ient s w it h
st rabismus or acquired visual loss w ho have a jerk nyst agmus in t he direct ion of
t he f ixing eye (i. e. , right -beat ing nyst agmus w hen f ixing w it h t he right eye and
lef t -beat ing nyst agmus w hen f ixing w it h t he lef t eye) [128] . Pat ient s w it h inf ant ile
uniocular blindness may have a bilat eral horizont al nyst agmus t hat represent s a
manif est nyst agmus of t he lat ent t ype [450] . These pat ient s of t en have a f amily
hist ory of st rabismus; t he monocular blindness (opacit y of t he media or
suppression) act s as an occluder, manif est ing w hat w ould have been lat ent
nyst agmus.
As not ed earlier, pendular nyst agmus is of t en congenit al. Acqui red pendul ar
nystagmus may be w holly horizont al, w holly vert ical, or have mixed component s
(circular, ellipt ical, or w indmill pendular nyst agmus). Pendular nyst agmus may be
symmet ric, dissociat ed, or even monocular and of t en causes dist ressing
oscillopsia and decreased visual acuit y [29, 40, 68, 498] . Damage t o t he
dent at orubroolivary pat hw ays (G ui l l ai n-Mol l aret tri angl e) is f ound in some cases
of acquired pendular nyst agmus, w hich is most of t en caused by mult iple
sclerosis, st roke, or t umor of t he brainst em or ot her post erior f ossa st ruct ures.
I n mult iple sclerosis, pendular nyst agmus may be a sign of cerebellar nuclear
involvement [29] , or result f rom opt ic neuropat hy, but t he most consist ent f inding
on MRI is a lesion in t he dorsal pont ine t egment um, perhaps aff ect ing t he cent ral
t egment al t ract [68] . I n a st udy of 27 pat ient s w it h acquired pendular nyst agmus,
magnet ic resonance images w ere charact erized by mult iple areas of abnormal
signal w it h st at ist ically signif icant ones occurring in areas cont aining t he red
nucleus, t he cent ral t egment al t ract , t he MVN, and t he inf erior olive [498] . The
abundance of abnormal MRI signals, predominant ly in t he pons but also in t he
midbrain and t he medulla, suggest s t hat large or mult iple st ruct ural lesions may
be required t o elicit pendular nyst agmus. Acquired convergence-induced pendular
nyst agmus may occur w it h mult iple sclerosis [69] .
O t her causes of acquired binocular pendular nyst agmus include Pelizaeus-
Merzbacher disease, mit ochondrial cyt opat hy, Cockayne's syndrome, neonat al
adrenoleukodyst rophy (a peroxisomal disorder), and t oluene addict ion [465,
480] . Pendular nyst agmus may also appear w it h blindness or monocular loss of
vision; in t he lat t er case, it may be monocular (see preceding t ext ). Binocular
visual loss may cause nyst agmus t hat has bot h horizont al and vert ical
component s t hat change direct ion over seconds or minut es (i. e. , a w andering null
point ) [292] . Blind pat ient s may have wi ndmi l l nystagmus, in w hich t here are
repeat ed oscillat ions in t he vert ical plane alt ernat ing w it h repeat ed oscillat ions in
t he horizont al plane.
Hori zontal pendul ar pseudonystagmus has been described in pat ient s w it h
horizont al essent ial head t remor and bilat eral vest ibular dysf unct ion [122, 810] .
The def icient vest ibulo-ocular ref lex result s in ocular oscillat ions in space w hen
t he head oscillat es and f unduscopy reveals a f ine pendular mot ion of t he eyes
t hat is reduced by f irm support of t he head. Yen et al. described t w o renal
t ransplant pat ient s w ho developed pseudonyst agmus and oscillopisa caused by
immunosuppressant (t acrolimus)-induced head t remor and gent amicin-induced
vest ibulopat hy [854] . Alt hough t he pat ient s w ere init ially t hought t o have
nyst agmus, closer observat ion revealed no t rue nyst agmus but correct ive
saccades compensat ing f or an absent vest ibulo-ocular ref lex during t he head
t remor (pseudonyst agmus). Typically pat ient s w it h vest ibulo-ocular impairment
have only head movement –induced oscillopsia, but t hese pat ient s had const ant
oscillopsia because t he visual t racking syst em (smoot h pursuit ) could not
compensat e f or t he loss of vest ibular f unct ion at immunosuppressant -induced
head oscillat ion >1 Hz.
Head-shaki ng nystagmus–Head-Shaki ng Nystagmus ( HSN) ref ers t o t he
nyst agmus induced by head oscillat ion, and usually beat s t o t he healt hy side in
unilat eral peripheral vest ibulopat hy [311] . I n perverted HSN–Perverted Hsn
(pHSN), t he nyst agmus develops in t he plane ot her t han t hat being st imulat ed,
t hat is, dow nbeat or upbeat af t er horizont al head oscillat ion. pHSN has been
report ed in diff use cerebellar degenerat ion, w it h f ocal caudal cerebellar st roke,
or w it h medullary lesions and signif ies cent ral vest ibular lesion [425] .
Pal atal myocl onus is a cont inuous rhyt hmic involunt ary movement of t he sof t
palat e t hat may be accompanied by synchronous movement s of ot her adjacent
st ruct ures, such as t he f ace, pharynx, larynx, or diaphragm. The associat ion of
pendular nyst agmus w it h palat al myoclonus is not inf requent and t he condit ion is
t hen t ermed ocul opal atal myocl onus [ 300, 752] . O culopalat al myoclonus may be
of t w o t ypes [563] .
1. A lat eral f orm, consist ing of jerky, nyst agmoid movement s w it h simult aneous
oblique and rot at ory component s associat ed (and synchronous) w it h
lat eralized palat al myoclonus (in t his f orm, t he eye on t he side of t he
myoclonus int ort s as it rises and ext ort s as it f alls w hile t he opposit e eye
ext ort s as it rises and int ort s as it f alls).
2. A midline f orm in w hich vert ical t o-and-f ro pendular eye movement s occur
synchronous w it h symmet ric bilat eral palat al myoclonus.
I t has been post ulat ed t hat t he generat ion of oculopalat al myoclonus involves
vest ibulo-ocular ref lex adapt ion mediat ed by t he cerebellar f locculus as f loccular
int egrit y is preserved in most pat ient s [563] . The lat eral f orm implies unilat eral
disease w hile t he midline f orm indicat es bilat eral disease. Damage t o t he
dent at orubroolivary pat hw ays (G uillain-Mollaret t riangle) is f ound in cases of
oculopalat al myoclonus, w hich is most of t en caused by mult iple sclerosis or
vascular lesions of t he brainst em. MRI of t en show s enlargement of t he inf erior
olivary nuclei [752] .
There may be an associat ion bet w een t he one-and-a-half syndrome (see
preceding t ext ) and oculopalat al myoclonus [841] . I n f ive pat ient s w it h one-and-
a-half syndrome and f acial nerve palsy, oculopalat al myoclonus developed in 4
mont hs t o 3 years. I nvolvement of t he f acial nerve may predict subsequent
development of oculopalat al myoclonus.
Binocular Symmetric Jerk Nystagmus

Bi nocul ar symmetri c conjugate jerk nystagmus may be divided int o t hose
present ing spont aneously and t hose t hat are is induced [128] . Spont aneous jerk
nyst agmus may be f urt her divided int o f orms present in primary posit ion and
f orms present predominant ly on eccent ric gaze.
Spont aneous symmet ric conjugat e jerk nyst agmus t hat occurs in primary posit ion
may be predominant ly horizont al, t orsional, or vert ical. Spont aneous symmet ric
conjugat e jerk nyst agmus in primary gaze t hat is predominant ly horizont al
includes congenit al nyst agmus (see preceding t ext ), lat ent nyst agmus (see
preceding t ext ), vest ibular nyst agmus, PAN, drug-induced nyst agmus, and
epilept ic nyst agmus. Spont aneous symmet ric conjugat e jerk nyst agmus in
primary gaze t hat is purely t orsional is a f orm of cent ral vest ibular nyst agmus.
Spont aneous symmet ric conjugat e jerk nyst agmus in primary gaze t hat is
predominant ly vert ical includes UBN and DBN.
Horizont al nyst agmus in t he primary posit ion is of t en t he result of peripheral
vest ibular disease. Vesti bul ar nystagmus has a linear (const ant velocit y) slow
phase. The horizont al component is diminished w hen t he pat ient lies w it h t he
int act ear dow n and is exacerbat ed w it h t he aff ect ed ear dow n. Peripheral
vest ibular lesions induce a t endency f or t he eyes t o drif t in a direct ion parallel t o
t he plane in w hich t he diseased canal lies. Horizont al nyst agmus w it h t he slow
component t ow ard t he lesion (t he opposit e VN drive t he eyes t ow ard t he
diseased side) result s f rom unilat eral horizont al canal or t ot al labyrint hine
dest ruct ion. I n t he lat t er case, t here is a t orsional slow component causing t he
upper part of t he globe t o rot at e t ow ard t he lesioned side. Alt hough const ant f or
a part icular posit ion of gaze, t he slow -phase velocit y is great er w hen t he eyes
are t urned in t he direct ion of t he quick component (Alexander's law ). Nyst agmus
due t o peripheral vest ibular disease is most prominent , or only becomes
apparent , w hen f ixat ion is prevent ed. Bot h peripheral and cent ral vest ibular
nyst agmus may vary w it h head posit ion and movement , but peripheral nyst agmus
changes af t er a lat ency period f ollow ing t he post ural change and t ends t o
f at igue. Hypervent ilat ion may occasionally precipit at e acut e vest ibular imbalance
and nyst agmus in pat ient s w it h acoust ic neuroma or af t er vest ibular neurit is
[ 480] . Hypervent ilat ion-induced nyst agmus is usually a recovery nyst agmus, w it h
slow phases direct ed aw ay f rom t he side of t he lesion, perhaps due t o
hypervent ilat ion improving nerve conduct ion on t he lesioned side and inducing
imbalance of act ivit y w it hin t he VN t hat had been cent rally adapt ed [480] . Tw o
main diff erences ident if y peripheral and cent ral vest ibular nyst agmus: t he eff ect
of f ixat ion and t he direct ion of nyst agmus. Fixat ion (i. e. , int act f ixat ion and
pursuit st abilizat ion syst ems) suppresses t he peripheral but not t he cent ral
nyst agmus. Also, peripheral nyst agmus, part icularly w hen vert ical, usually has a
t orsional component . Pure vert ical or t orsional nyst agmus is cent ral.
O ccasionally, a peripheral vest ibular lesion may cause a nyst agmus w it h t he
horizont al slow component away f rom t he lesion. This is most likely a recovery
nystagmus due t o t he eff ect s of cent ral vest ibular adapt ive processes.
Peripheral vest ibular disease is suspect ed w hen t he nyst agmus is associat ed
w it h subject ive vert igo.
Cent ral vest ibular disease (e. g. , brainst em inf arct ion) is suspect ed w hen
associat ed neurologic signs and sympt oms of brainst em dysf unct ion are present .
Wit h peri odi c al ternati ng nystagmus–Periodic Alt ernat ing Nyst agmus (PAN), t he
eyes exhibit primary posit ion nyst agmus, w hich, af t er 60 t o 120 seconds, st ops
f or a f ew seconds and t hen st art s beat ing in t he opposit e direct ion [202] . A f ew
beat s of DBN, UBN, or square-w ave jerks may appear in t he int erval bet w een
alt ernat ing sidebeat nyst agmus. Horizont al jerk nyst agmus in t he primary posit ion
not associat ed w it h vert igo is usually PAN [128] . This disorder may be
associat ed w it h periodic alt ernat ing oscillopsia, periodic alt ernat ing gaze, or
periodic alt ernat ing skew deviat ion [790] .
PAN may be congenit al, but it is of t en acquired and caused by disease
processes at t he craniocervical junct ion [333, 465, 480, 782] . PAN may be
provoked by an at t ack of Meniere's disease [147] and w as associat ed w it h
periodic alt ernat ing skew deviat ion in a pat ient w it h cerebellar degenerat ion
[ 488] . Also, PAN may be a prominent f inding in some pat ient s w it h Creut zf eldt -
Jakob disease, especially cases associat ed w it h cerebellar at axia; t he head
t urn, how ever, w as in t he same direct ion as t he current slow eye deviat ion (w hen
t he cases had progressed t o periodic alt ernat ing gaze deviat ion), suggest ing
t hat t he head t urns in t hese cases w ere not adapt ive mechanisms but rat her a
manif est at ion of t he underlying vest ibular oscillat ion [297] (Table 8-11). A
possible variant of PAN, peri odi c al ternati ng wi ndmi l l nystagmus, has been
described in blind pat ient s and consist s of oscillat ions in bot h t he horizont al and
vert ical planes, 90 degrees out of phase.
The nodulus and uvula of t he cerebellum maint ain inhibit ory cont rol over
vest ibular rot at ional responses by using t he neurot ransmit t er G ABA and over t he
course of post rot at ional nyst agmus. Theref ore, f ollow ing ablat ion of t hese
st ruct ures, t he post rot at ional response is excessively prolonged, so t hat normal
vest ibular repair mechanisms act t o reverse t he direct ion of t he nyst agmus
[ 480] , w hich may result in PAN. Theref ore, PAN is likely caused by lesions of t he
cerebellar uvul a and nodul us or t heir connect ions w it h t he brainst em VN. This
vest ibulo-cerebellar circuit w ould ordinarily be blocked by visual f ixat ion, smoot h
pursuit , and opt okinet ic mechanisms; t heref ore, anot her prerequisit e f or PAN is
t hat visual st abilizat ion syst ems must be impaired eit her by loss of vision (e. g. ,
cat aract s, vit reous hemorrhage) or cerebellar f loccular disease. Baclof en, a
G ABA-B agonist , may abolish PAN, adding f urt her evidence t o t he import ance of
t he nodulus and uvula in t he generat ion of PAN.
TABLE 8-11 Etiologies of Periodic Alternating

Nystagmus
Congenital (may be associated with albinism)

Arnold-Chiari malformation and other malformations
of the craniocervical junction
Cerebellar degenerations (e.g., spinocerebellar
ataxia type 6), occasionally with anti-glutamic acid
decarboxylase antibodies
Ataxia-telangiectasia
Cerebellar masses, including tumors, abscesses,
and cysts
Brainstem infarction
Cerebellar infections, including syphilis and
Creutzfeldt-Jacob disease
Hepatic encephalopathy
Encephalitis
Trauma
Multiple sclerosis
Anticonvulsant medications (e.g., phenytoin
intoxication)
Lithium
Following visual loss (e.g., due to cataract or
vitreous hemorrhage)
Epileptic periodic alternating nystagmus (after
hypoxic encephalopathy)
Provoked by an attack of Meniere's disease
Drug-i nduced nystagmus may be predominant ly horizont al, vert ical, rot at ory, or,
most commonly, mixed. I t is most of t en seen w it h t ranquilizing medicat ions and
ant iconvulsant s. Alt hough drug-induced nyst agmus is more of t en evident w it h
eccent ric gaze (see subsequent t ext ), it may also be evident in primary gaze
[ 128, 645] .
Nyst agmus may occur as an epilept ic phenomena. Epi l epti c nystagmus is usually
horizont al, may be seen w it h epilept if orm act ivit y ipsilat eral or cont ralat eral t o
t he direct ion of t he slow component of t he nyst agmus, and is of t en associat ed
w it h alt ered st at es of consciousness, alt hough consciousness may be preserved
during t he at t acks [261, 329, 372, 394, 395, 737, 793] . There are t w o
post ulat ed mechanisms f or t he eye deviat ion in epilept ic nyst agmus [261, 329,
372, 394, 395, 793] . I psiversive eye deviat ion, w it h eye movement recordings
and EEG show ing seizure-induced ipsilat eral linear slow phases, is post ulat ed t o
result f rom st imulat ion of t he smoot h pursuit region in t he t emporo-occipit al
cort ex. I f eye velocit y is high or t he eye reaches a f ar
eccent ric port ion in t he orbit , a normal reset t ing quick phase eye movement
occurs af t er each slow phase, result ing in nyst agmus. Cont raversive eye
deviat ions, w it h eye movement recordings and EEG show ing seizure-induced
cont ralat eral quick phases, is t hought t o be due t o st imulat ion of t he saccade-
cont rolling regions of t he t emporo-occipit al or f ront al cort ex. I f gaze holding is
def ect ive (e. g. , t he neural int egrat ion is “leaky”), t hen velocit y-decreasing slow
phases bring t he eyes back t o t he midline af t er each quick phase, result ing in
nyst agmus. Epilept ic PAN has been described (af t er hypoxic encephalopat hy)
[ 555] .
Spont aneous jerk nyst agmus t hat is purel y torsi onal is a rare f orm of cent ral
vest ibular nyst agmus. I t is of t en diff icult t o det ect except by t he observat ion of
t he conjunct ival vessels or by not ing t he direct ion of ret inal movement s on eit her
side of t he f ovea. Purely t orsional nyst agmus may be present in primary gaze or
elicit ed by head posit ioning or gaze deviat ion [500] . Purely t orsional nyst agmus
may be seen w it h brainst em and post erior f ossa lesions, such as t umors,
syringobulbia, syringomyelia w it h Arnold-Chiari malf ormat ion, lat eral medullary
syndrome, mult iple sclerosis, t rauma, vascular anomalies, post -encephalit is, and
sarcoidosis, and as part of t he st iff -person syndrome [465, 500, 545, 577, 734] .
Cont ralesionally beat ing t orsional nyst agmus may be due t o a midbrain lesion
involving t he rost ral int erst it ial nucleus of t he MLF, w hile lesions of t he I NC in t he
midbrain cause ipsilesional t orsional nyst agmus [342, 343] . Torsional nyst agmus
occurring only during vert ical pursuit has been described w it h cavernous
angiomas of t he middle cerebellar peduncle [237] . Nonrhyt hmic but cont inuous
t orsional eye movement s have been report ed as a paraneoplast ic process [664] .
Predominantly Vertical Jerk Nystagmus

Spontaneous jerk nystagmus i n pri mary gaze t hat is predominant ly vert ical
includes UBN and DBN [52, 130, 613] .
DBN is usually present in primary posit ion, but is great est w hen t he pat ient looks
dow n (Alexander's law ) and t o one side. O n upw ard gaze, t he nyst agmus is less
pronounced or disappears complet ely. DBN is of t en associat ed w it h horizont al
gaze-evoked nyst agmus; convergence may increase, suppress, or convert t he
nyst agmus t o UBN. The nyst agmus may occasionally be dysjunct ive, being more
vert ical in one eye and t orsional in t he ot her eye, especially w hen associat ed
w it h an int ernuclear opht halmoplegia (as seen earlier). DBN may occur w it h
cervicomedullary junct ion disease, midline medullary lesions, post erior midline
cerebellar lesions, or diff use cerebellar disease [318, 474, 824, 848] . Most
lesions responsible f or DBN aff ect t he vest ibulocerebellum (f locculus,
paraf locculus, nodulus, and uvula) and t he underlying medulla. Def icient drive by
t he post erior SCCs, w hose cent ral project ions cross in t he f loor of t he f ourt h
vent ricle, has been post ulat ed as an explanat ion f or DBN. I nt errupt ion of
dow nw ard vest ibulo-ocular ref lex pat hw ays, w hich synapse in t he MVN and cross
in t he medulla (beneat h t he NPH) t o reach t he cont ralat eral MLF, w ould result in
upw ard smoot h eye drif t and a dow nw ard correct ive saccade. Cerebellar,
especially f loccular and uvulonodular, lesions may cause t his nyst agmus by
disinhibit ion of t he cerebellar eff ect on t he VN. The cerebellar f locculus cont ains
Purkinje cells t hat send inhibit ory project ions t o t he ant erior canal but not t he
post erior canal cent ral pat hw ays; t heref ore, disinhibit ion w ould lead t o DBN.
Damage t o t he nuclei proposit us hypoglossi and t he medial VN (t he neural
int egrat or) in t he medulla has also been suggest ed as t he cause of t he
nyst agmus [169] . A pat ient w it h acut e mult iple sclerosis w it h a lesion of t he
caudal medulla (w hich cont ains t he nucleus Roller and nucleus int ercalat us)
developed DBN upon horizont al head oscillat ions (pHSN) [534a. Et iologies of
DBN [77, 169, 216, 310, 465, 480 are list ed in Table 8-12. Intermi ttent DBN,
accompanied by episodic vert ical oscillopsia, may be an early sign of Arnold-
Chiari malf ormat ion [849] and w as elicit ed by head ext ension and rot at ion in a
pat ient w it h a vermian arachnoid cyst w it h associat ed obst ruct ive hydrocephalus
[ 145] .
Damage t o t he cent ral project ions of t he ant erior SCCs, w hich t end t o deviat e
t he eyes superiorly, has been suggest ed t o explain UBN. UBN is usually w orse in
upgaze (Alexander's law ) and, unlike DBN, it usually does not increase on lat eral
gaze [52] . Convergence may increase or decrease t he nyst agmus, or convert
DBN t o UBN [319, 346] . Damage t o t he vent ral t egment al pat hw ays, w hich may
link t he superior VN t o t he SR and I O subnuclei of t he oculomot or nuclei, may
cause t he eyes t o glide dow n, result ing in UBN [641] . Medullary disease may
cause UBN as may lesions of t he ant erior cerebellar vermis, perihypoglossal and
inf erior olivary nuclei of t he medulla, pont ine t egment um, brachium conjunct ivum,
midbrain, and brainst em diff usely [130, 318, 346, 391, 419, 557, 786] . Medullary
lesions invariably involve t he perihypoglossal nucleus and adjacent MVN, nucleus
int ercalat us, and vent ral t egment um, w hich cont ain project ions f rom VN t hat
receive input s f rom t he ant erior SCCs. Primary posit ion UBN may occur w it h
unilat eral medial
medullary inf arct ion, likely due t o impairment of t he vert ical posit ion-t o-velocit y
neural int egrat or in t he nucleus int ercalat us of St aderini, a st ruct ure in t he
paramedian caudal medulla locat ed caudal t o t he VN and t o t he most rost ral of
t he perihypoglossal nuclei (NPH and nucleus of Roller) [347, 376] . Lesions of
t his st ruct ure may cause primary posit ion UBN increased in dow nw ard gaze
[ 585] . Et iologies of UBN [465, 480, 786 are out lined in Table 8-13. Primary
posit ion UBN and ocular lat eral pulsion (i. e. , saccadic overshoot or hypermet ria
aw ay f rom t he lesion and hypomet ria t ow ard t he lesion) have been described
w it h hemispheric cerebellar lesions [76] . Primary posit ion UBN combined w it h
binocular ellipt ical pendular nyst agmus is charact erist ic of Pelizaeus-Merzbacher
disease [789] . Bow-ti e nystagmus, in w hich quick phases are direct ed obliquely
upw ard w it h horizont al component s alt ernat ing t o t he right and lef t , is probably a
variant of UBN [480] .
TABLE 8-12 Etiologies of Dow nbeat Nystagmus
Craniocervical anomalies, including cerebellar ectopia,

Arnold-Chiari malformation, platybasia, basilar
invagination, and Paget's disease
Familial cerebellar degenerations including
spinocerebellar ataxia 6 and episodic ataxia type 2
Multiple system atrophy
Posterior fossa tumors
Increased intracranial pressure (e.g., due to supra-
tentorial mass) and hydrocephalus
Brainstem or cerebellar infarction, anoxia, or
hemorrhage
Dolichoectasia of the vertebrobasilar artery
Intermittent vertebral artery compression by an
osteophyte
Encephalitis, including herpes simplex encephalitis and
HTLV-1 infection
Heat stroke
Cephalic tetanus
Multiple sclerosis and other leukodystrophies
Syringomyelia/syringobulbia
Trauma
Alcohol, including alcohol-induced cerebellar
degeneration
W ernicke's encephalopathy
Paraneoplastic cerebellar degeneration (including
testicular cancer with anti-Ta antibody)
High serum and cerebrospinal fluid titers of glutamic
acid decarboxylase antibodies have been associated
with downbeat nystagmus
Superficial siderosis of the CNS
Congenital
Vitamin B12 deficiency
Thiamine deficiency
Magnesium deficiency
Drugs, including lithium, toluene, and anticonvulsants
(e.g., phenytoin, carbamazepine, felbamate)
Transient finding in otherwise normal infants
Idiopathic
CNS = central nervous system.

The pat hophysiology of spont aneous UBN and DBN w as review ed and
summarized by Pierrot -Deseilligny and Milea [613] . UBN due t o pont ine lesions
could result f rom damage t o t he vent ral t egment al t ract –Vent ral Tegment al Tract
(VTT), originat ing in t he superior vest ibular nucleus–Superior Vest ibular Nucleus
(SVN), coursing t hrough t he vent ral pons and t ransmit t ing excit at ory upw ard
vest ibular signals t o t he t hird nerve nucleus. A VTT lesion probably leads t o
relat ive hypoact ivit y of t he drive t o t he mot oneurons of t he elevat or muscles
w it h, consequent ly, an imbalance bet w een t he dow nw ard and upw ard syst ems,
result ing in a dow nw ard slow phase. The result s observed in int ernuclear
opht halmoplegia suggest t hat t he MLF is involved in t he t ransmission of bot h
upw ard and dow nw ard vest ibular signals. Since no clinical cases of DBN due t o
f ocal brainst em damage have been report ed, it may be assumed t hat t he
t ransmission of dow nw ard vest ibular signals depends only upon t he MLF,
w hereas t hat of upw ard vest ibular signals involves bot h t he MLF and t he VTT.
The main f ocal lesions result ing in DBN aff ect t he cerebellar f locculus and/ or
paraf locculus. Apparent ly, t his st ruct ure t onically inhibit s t he SVN and it s
excit at ory eff erent t ract , (i. e. , t he VTT) but not t he dow nw ard vest ibular syst em.
Theref ore, a f loccular lesion could result in a disinhibit ion of t he SVN–VTT
pat hw ay w it h, consequent ly, relat ive hyperact ivit y of t he drive t o t he
mot oneurons of t he elevat or muscles, result ing in an upw ard slow phase. UBN
also result s f rom lesions aff ect ing t he caudal medulla (nucleus of Roller and a
cell group of t he PMT). An area in t his region could f orm part
of a f eedback loop involved in upw ard gaze holding, originat ing in a collat eral
branch of t he VTT and comprising t he caudal medulla, t he f locculus, and t he
SVN, successively. Theref ore, Pierrot -Deseilligny and Milea suggest t hat t he
main t ypes of spont aneous vert ical nyst agmus due t o f ocal cent ral lesions result
f rom a primary dysf unct ion of t he SVN–VTT pat hw ay, w hich becomes hypoact ive
af t er pont ine or caudal medullary lesions, t hereby elicit ing UBN, and hyperact ive
af t er f loccular lesions, t hereby elicit ing DBN. Last ly, since gravit y inf luences UBN
and DBN and may f acilit at e t he dow nw ard vest ibular syst em and rest rain t he
upw ard vest ibular syst em, it w as hypot hesized t hat t he excit at ory SVN–VTT
pat hw ay, along w it h it s specif ic f loccular inhibit ion, has developed t o count eract
t he gravit y pull. This anat omic hyperdevelopment is apparent ly associat ed w it h a
physiologic upw ard velocit y bias, since t he gain of all upw ard slow eye
movement s is great er t han t hat of dow nw ard slow eye movement s in normal
human subject s and in monkeys [613] .
TABLE 8-13 Etiologies of Upbeat Nystagmus
Primary cerebellar degenerations and atrophies

Arnold-Chiari malformation
Posterior fossa tumors
Brainstem or cerebellum infarction or hemorrhage
Cavernous malformation of brainstem
Multiple sclerosis
Meningitis and brainstem encephalitis
Thalamic arteriovenous malformation
Behcet's syndrome
Congenital, including cases associated with Leber's
congenital amaurosis and other congenital anterior
visual pathway disorders
Pelizaeus-Merzbacher disease
Creutzfeldt-Jakob disease
Fisher syndrome (ataxia, areflexia, and
ophthalmoplegia)
Middle ear disease
Organophosphate poisoning
Tobacco induced
Anticonvulsant intoxication
Cyclosporine A
Paraneoplastic syndrome with testicular cancer and
anti-Ta antibodies
Transient finding in otherwise healthy neonates

Binocular Symmetric Jerk Nystagmus Present in

Eccentric Gaze or Induced by Various Maneuvers
Spont aneous binocular conjugat e symmet ric jerk nyst agmus t hat is induced by
eccent ric gaze (gaze-evoked nystagmus) includes nyst agmus due t o
brainst em/ cerebellar disease, Bruns' nyst agmus, drug-induced nyst agmus,
physiologic nyst agmus, rebound nyst agmus, and convergence-induced
nyst agmus. DBN and UBN may only occur on dow nw ard or upw ard gaze,
respect ively (see preceding t ext ).
Wit h gaze-evoked nystagmus, t he eyes f ail t o remain in an eccent ric posit ion of
gaze but drif t t o midposit ion. The velocit y of t he slow component decreases
exponent ially as t he eyes approach midposit ion. A “leaky” neural int egrat or or
cerebellar (especially vest ibulocerebellar) lesion may result in t his t ype of
nyst agmus, w hich is more pronounced w hen t he pat ient looks t ow ard t he lesion.
Cerebellopont ine angle t umors may cause Bruns' nystagmus, a combinat ion of
ipsilat eral large-amplit ude, low -f requency nyst agmus t hat is due t o impaired
gaze holding, and cont ralat eral small-amplit ude, high-f requency nyst agmus t hat
is due t o vest ibular impairment [480] . G aze-evoked nyst agmus may be a side
eff ect of medicat ions, including ant iconvulsant s, sedat ives, and alcohol. G aze-
evoked nyst agmus has been described w it h adult -onset Alexander's disease w it h
t he involvement of t he middle cerebellar peduncles and dent at e nuclei [510] and
is also a f eat ure of f amilial episodic vert igo and at axia t ype 2 t hat is responsive
t o acet azolamide [51, 53, 110] . Physiologic or endpoint nyst agmus is a benign
low -amplit ude jerk nyst agmus w it h t he f ast component direct ed t ow ard t he f ield
of gaze. I t usually ceases w hen t he eyes are brought t o a posit ion somew hat
less t han t he ext remes of gaze.
Rebound nystagmus is seen in some pat ient s w it h brainst em and/ or cerebellar
disease (e. g. , olivocerebellar at rophy, brainst em/ cerebellar t umor or st roke,
Marinesco-Sjögren syndrome, Dandy-Walker cyst , G erst mann-St raussler-
Scheinker disease, adult -onset Alexander's disease, et c. ) [95, 491, 510, 852] .
Af t er keeping t he eyes eccent ric f or some t ime, t he original gaze-evoked
nyst agmus may w ane and act ually reverse direct ion so t hat t he slow component
is direct ed cent rif ugally (cent ripit al nyst agmus); it becomes obvious if t he eyes
are ret urned t o midposit ion (rebound nyst agmus). Rebound nyst agmus probably
ref lect s an at t empt
by t he brainst em or t he cerebellar mechanisms t o correct f or t he cent ripet al drif t

of gaze-evoked nyst agmus [480] .
Convergence may change nyst agmus by convert ing dow nbeat t o upbeat , upbeat
t o dow nbeat , or pendular t o upbeat . Convergence-evoked nyst agmus is usually
vert ical (upbeat is more common t han dow nbeat ) and seen most commonly w it h
mult iple sclerosis or brainst em inf arct ion [592] . Convergence may also increase
or decrease t he amplit ude of nyst agmus and may evoke horizont al (congenit al or
acquired pendular and jerk) or vert ical (upbeat or dow nbeat ) nyst agmus [703] .
Convergence-induced pendular nyst agmus has been described as a congenit al
phenomenon (conjugat e) and as an acquired phenomenon (disjunct ive) w it h
mult iple sclerosis [69, 592, 703] . The eff ect s of convergence on nyst agmus are
not t o be conf used w it h convergence nyst agmus in w hich a slow abduct ion of t he
eyes is f ollow ed by quick adduct ion (see preceding t ext ).
Binocular symmet ric conjugat e jerk nyst agmus t hat is induced includes
opt okinet ic nyst agmus, rot at ional/ caloric vest ibular nyst agmus, posit ional
nyst agmus, Valsalva-induced nyst agmus, and hypervent ilat ion-induced nyst agmus
[ 128, 480] . The f irst t w o t ypes of induced nyst agmus are physiologic and,
alt hough abnormalit ies of t hese responses may aid in clinical diagnosis, t hey w ill
not be discussed f urt her.
Posi ti onal verti go of the beni gn paroxysmal type, also know n as benign
paroxysmal posit ioning vert igo or posit ional nyst agmus, is usually “idiopat hic”
and possibly relat ed t o degenerat ion of t he macula of t he ot olit h organ or t o
lesions of t he post erior SCC [49, 54, 102, 103, 260, 461, 827] . I t has been
proposed t hat ot oconia det ached f rom t he ot oconial layer (by degenerat ion or
t rauma) gravit at e and set t le on t he cupula of t he post erior canal causing it t o
become heavier t han t he surrounding endolymph and t heref ore sensit ive t o
changes in t he direct ion of gravit y (w it h posit ional change). Af t er rapid head t ilt
t ow ard t he aff ect ed ear or f ollow ing head ext ension, w hen t he post erior SCC is
moved in t he specif ic plane of st imulat ion, an ampullof ugal def lect ion of t he
cupula occurs, w it h a rot at ional vert igo and concomit ant nyst agmus. Some
pat ient s show a st rong horizont al nyst agmus induced by lat eral head posit ioning
suggest ing lat eral (rat her t han post erior) SCC irrit at ion (lat eral canal or
horizont al canal variant of benign paroxysmal posit ional vert igo) [50, 190] . O t her
causes of posit ional vert igo include t rauma, inf ect ion, labyrint hine f ist ula,
ischemia, demyelinat ing disease, Arnold-Chiari malf ormat ion, and, rarely,
post erior f ossa t umors or vascular malf ormat ions [461] .
Besides paroxysmal posit ional nyst agmus, pat ient s of t en also exhibit st at ic
(persist ent ) posit ional nyst agmus w hile lying in a lat eral posit ion. This st at ic
nyst agmus is predominant ly horizont al w it h minimal vert ical component [49] .
Paroxysmal vert igo induced by cert ain head posit ions is t he most common
complaint ; t he pat ient is asympt omat ic bet w een bout s. The Nylen-Barany
maneuver (briskly t ilt ing t he pat ient 's head backw ard and t urning it 45 degrees t o
one side) allow s a diff erent iat ion bet w een a peripheral and a cent ral origin f or
posit ional vert igo.
Nyst agmus induced by t he Val sal va maneuver may occur w it h Arnold-Chiari
malf ormat ion or perilymph f ist ulas [480] . Hypervent ilat ion may induce nyst agmus
in pat ient s w it h t umors of t he eight h CN (e. g. , acoust ic neuroma or epidermoid
t umors), af t er vest ibular neurit is, or cent ral demyelinat ing lesions [480, 536] .
Hypervent ilat ion-induced nyst agmus has t he slow phase aw ay f rom t he side of
t he lesion (an excit at ory or recovery nyst agmus) and is likely due t o t he eff ect of
hypervent ilat ion upon serum pH and calcium concent rat ion, w hich improves nerve
conduct ion in a marginally f unct ional, demyelinat ed nerve [480, 536] .
The superi or SCC dehi scence syndrome is charact erized by vert igo and
nyst agmus induced by sound (Tul l i o phenomenon) or changes of middle ear
(Hennebert sign) or int racranial pressure and is caused by bony dehiscence of
t he superior SCC [47, 199, 780] . These pat ient s may have head movement –
dependent oscillopsia. The sound- and pressure-induced nyst agmus is in t he
plane of t hat canal, and CT of t he t emporal bone show s dehiscence of t he bone
overlying t he aff ect ed superior SCC in every case. The basic mechanism f or t he
product ion of sympt oms and signs w it h t he syndrome is an int ernal perilymph
f ist ula—“a t hird w indow ”—so t hat sound and pressure changes displace
endolymph in t he ant erior canal, deviat ing t he cupula and excit ing or inhibit ing t he
ant erior canal nerve. By t riggering t he charact erist ic t orsional vert ical nyst agmus
in t he plane of t he superior SCC w it h eit her loud sounds or pressure changes in
t he middle ear or cerebrospinal f luid (CSF), t he diagnosis can usually be made
[ 47] . Tiliket e et al. report ed a pat ient w it h bilat eral superior canal dehiscence
syndrome w ho present ed w it h unusual manif est at ions including pulse-
synchronous vert ical pendular nyst agmus and Valsalva-induced, up and
count erclockw ise-beat ing jerk nyst agmus and suggest ed t hat normal
communicat ion bet w een t he
inner ears and t he int racranial space may explain t he vert ical pendular and
pulse-synchronous nyst agmus, modulat ed by increased int racranial pressure
[ 780] .
Saccadic Intrusions
I nappropriat e saccades, or saccadi c i ntrusi ons, int erf ere w it h macular f ixat ion of
an object of int erest . The essent ial diff erence bet w een nyst agmus and saccadic
int rusions lies in t he init ial eye movement t hat t akes t he line of sight aw ay f rom
t he object of regard [480] . For nyst agmus, it is a slow drif t or slow phase as
opposed t o an inappropriat e saccadic movement t hat int rudes on st eady f ixat ion.
Saccadic int rusions are discussed in t he preceding t ext .
Lid Nystagmus
Lid nyst agmus ref ers t o eyelid t w it ches t hat are synchronous w it h t he f ast phase
of horizont al nyst agmus on lat eral gaze. I t has been ascribed t o lat eral medullary
disease, w here it may be inhibit ed by near eff ort . Lid nyst agmus may also be
provoked by convergence (Pi ck's si gn) w it h cerebellar or medullary pat hology. I n
t his sit uat ion, it consist s of a slow dow ndrif t of t he lid correct ed by an upw ard
f lick. Rhyt hmic upw ard jerking of t he eyelids may be associat ed w it h vert ical
nyst agmus, palat al myoclonus, or convergence-ret ract ion nyst agmus. I n pat ient s
w it h vert ical gaze limit at ion due t o Fisher syndrome, lid nyst agmus may be
evoked by upw ard movement s of t he head in at t empt ed up-gaze. I rregular lid
t remor or lid f lut t er can occur in parkinsonism and cert ain met abolic diseases
(e. g. , G aucher's disease) [574] .
The Eyelids
I n normal adult s, t he upper lid just covers t he upper cornea, and t he low er lid
lies slight ly below t he inf erior corneal margin. Eyelid opening occurs w it h
cont ract ion of t he LP superioris muscle, innervat ed by t he oculomot or nerve.
Accessory muscles include Müller's muscle (sympat het ic innervat ed), w hich is
embedded in t he levat or and insert s mainly int o t he t arsal plat e, and t he f ront alis
muscle (innervat ed by t he t emporal branch of t he f acial nerve), w hich helps t o
ret ract t he lid in ext reme up-gaze [692] . Tonus in t he levat or normally parallels
t hat t o t he SR muscle, and, at ext reme dow n gaze, bot h muscles are complet ely
inhibit ed. How ever, t here is an inverse relat ionship bet w een t he levat or and t he
SR during f orced lid closure w here t he eye elevat es (Bel l 's phenomenon). Eyelid
closure occurs w hen levat or mot or neuronal act ivit y ceases; rapid and f irm eye
closure is a f unct ion of t he O O c muscles, w hich are cont rolled by t he f acial
nerve. Schmidt ke and But t ner-Ennever, in t heir excellent review of t he nervous
cont rol of eyelid f unct ion [692] , not ed t hat t he eyelid serves as a prot ect or of
t he eye in a number of separable f unct ions such as t he f ollow ing:
1. Tonic lid elevat ion w hen t he eyes are open

2. Volunt ary eye closure and eye-opening
3. I nvolunt ary adjust ment of t he eyelid t o t he vert ical globe posit ion, t hat is,
lid–eye coordinat ion
4. Periodic and ref lex blinking
5. Firm eye closure in prot ect ive and expressive act s, f or example, sneezing
I n t he f irst t hrough t hird f unct ions, only t he LP muscle is act ive; in t he f ourt h and
f if t h f unct ions, diff erent part s of t he O O c cont ract w hile t he levat or is
synchronously inhibit ed. Theref ore, lid posit ion, gent le eye closure, and lid–eye
coordinat ion are unaff ect ed by f acial nerve (CN VI I ) palsy, w hereas blinking and
f irm eye closure are impaired [692] . (Disorders of eyelid closure are discussed
in Chapt er 10)
The mot or neurons f or bot h levat or muscles are in t he unpaired cent ral caudal
nucleus–Cent ral Caudal Nucleus (CCN), locat ed at t he dorsal caudal pole of t he
oculomot or complex adjacent t o t he MR and SR subdivisions. Wit hin t he CCN,
mot or neurons of bot h levat ors are int ermixed; how ever, t he premot or cont rol of
each levat or is at least part ially lat eralized [692] . The close relat ionship of t he
lid posit ion t o t he level of arousal (i. e. , t he lids low er involunt arily w it h increasing
f at igue) has led some aut hors t o conclude t hat t he generat or of t he t onic levat or
mot or neuronal act ivit y lies in t he vent ral PAG of t he brainst em dorsal t o t he
caudal oculomot or nucleus (t he “supraocul omotor area”); because t his area
receives aff erent s f rom t he limbic syst em and ret icular f ormat ion, bot h regions
are f unct ionally involved in t he level of arousal. Theref ore, dest ruct ion of t he
PAG may cause pt osis. The cerebral cort ex, part icularly t he right hemisphere, is
associat ed w it h t he volunt ary cont rol of t onic levat or act ivit y, w hereas
ext rapyramidal dopaminergic pat hw ays inf luence blinks; t he region of t he nuclear
complex of t he post erior commissure–Nuclear Complex of t he Post erior
Commissure (NPC) is involved in lid–eye movement coordinat ion [692] .
The riMLF is t he principal premot or st ruct ure concerned w it h t he generat ion of
volunt ary vert ical saccades. Because of t he close lid–eye coordinat ion in all
t ypes of vert ical gaze changes, it is likely t hat t he premot or cont rol of saccadic
signals t o t he levat ors also comes f rom t he riMLF [692] .
How ever, t he cont rol of lid–eye coordinat ion also involves int erposed premot or
st ruct ures.
Ptosis
Drooping of t he eyelid (ptosi s or bl epharoptosi s) can be measured w it h t he
limbus or cent ral light ref lex used as ref erence point s. The usual posit ion of t he
adult upper eyelid margin is 1. 5 mm below t he upper limbus or 3 t o 4 mm above
t he light ref lex (t he margin ref lex dist ance). I f t he vert ical dist ance f rom limbus
t o limbus is 11 mm, t hen 4 mm of pt osis w ould result in bisect ion of t he cent er of
t he cornea or pupil by t he lid margin. The palpebral f issure and upper eyelid f old
are measured in t he primary posit ion of gaze. Normally, t he upper lid f old is
locat ed 5 t o 7 mm above t he upper lid margin. I t is also import ant t o measure
levat or f unct ion in t he evaluat ion of pt osis; t he amount of excursion of t he upper
eyelid f rom maximal st raight dow ngaze t o maximal upgaze may be det ermined
w it h a millimet er rule. Levat or f unct ion is usually 10 t o 12 mm or more
(cont ract ion of t he f ront alis muscle, w hich at t empt s t o overcome t he pt osis, must
be neut ralized by pressing t he t humb over t he cent er of t he pat ient 's eyebrow
w hile measuring). About 2 mm of movement probably is t ransmit t ed f rom
cont ract ion of t he SR muscle, so t hat a measurement of 2 mm or less can be
considered as no levat or f unct ion. Movement of 4 mm or less is classif ied as
poor levat or f unct ion; f rom 5 t o 7 mm as f air levat or f unct ion; and 8 mm or more
as good levat or f unct ion.
Pt osis has mult iple et iologies, including supranuclear lesions, lesions of t he
oculomot or complex, oculosympat het ic lesions, lesions of t he neuromuscular
junct ion, diseases of t he muscle, and local mechanical lid abnormalit ies [465] .
Acquired pt osis may be associat ed w it h marked loss of t he superior visual f ields
in bot h primary gaze and reading gaze [603] . A unilat eral pt osis may be
associat ed w it h eyelid ret ract ion on t he opposit e side due t o Hering's law of
equal innervat ion [526] .
Supranucl ear pt osis may be unilat eral or bilat eral [35, 39, 70, 578, 860] .
Unilat eral supranuclear pt osis is usually due t o a lesion of t he opposit e cerebral
hemisphere, especially ischemic lesions (e. g. , middle cerebral art ery inf arct ion)
[ 136] , but may also occur w it h t umor and art eriovenous malf ormat ions [502] .
Bilat eral supranuclear pt osis may be seen w it h unilat eral or bilat eral hemispheric
disease [578] . The preponderance of right -sided lesions in cases of cerebral
pt osis suggest s a dominance of t he right hemisphere in lid cont rol [35, 692] .
Large hemispheric inf arct s may cause complet e bilat eral pt osis t hat may be a
premonit ory sign of an impending herniat ion [35] . Bilat eral pt osis has been
described f ollow ing acut e right f ront o-t emporo-pariet al lobe lesions, all
associat ed w it h conjugat e gaze deviat ion t o t he right [484] . This pt osis is usually
t ransient , implying t hat t he int act hemisphere assumed mot or cont rol. Pt osis of
an unknow n mechanism may be not ed w it h parkinsonism [172] .
Bilat eral pt osis associat ed w it h supranuclear dow nw ard gaze paralysis, but w it h
ot her ocular mot or f unct ions relat ively int act , has been described w it h midbrain
glioma [132] . The dow nw ard gaze paralysis w as likely due t o bilat eral riMLF
impairment , w hereas t he bilat eral pt osis w as t hought t o be due t o t he t umor
dest roying t he PAG dorsal t o t he oculomot or nucleus (i. e. , t he “supraocul omotor
area”), w hich is concerned w it h premot or cont rol of t he levat or mot or neurons.
Bilat eral pt osis, t hought t o be due t o damage t o premot or levat or pat hw ays,
associat ed w it h select ive upw ard gaze paralysis has been described af t er minor
head t rauma in a pat ient w it h chronic hydrocephalus [746] .
Apraxi a of eyel i d openi ng ref ers t o an inabilit y t o open t he eyes volunt arily in t he
absence of pt osis or blepharospasm. Pat ient s w it h t his condit ion do not have
t rue pt osis but have diff icult y in overcoming levat or inhibit ion [487a. They must
t hrust t heir heads backw ard t o at t empt eyelid opening or must open t heir lids
manually. Apraxia of eyelid opening may occur w it h lesions of t he right
hemisphere or w it h bilat eral cerebral hemispheric lesions [384, 578] but may
also be seen w it h diseases of t he ext rapyramidal syst em [126, 288, 409, 444,
649] . A levodopa-responsive apraxia of eyelid opening may also occur in t he
absence of any ot her cent ral nervous syst em (CNS) signs [200] . The et iologies
of apraxia of eyelid opening are out lined in Table 8-14 [ 4, 5, 88, 375, 438, 465,
807] .
Aramideh et al. correlat ed t he clinical f indings of apraxia of eye-opening w it h
synchronous LP and O O c EMG recordings [23] . EMG w as charact erized by
eit her int ermit t ent LP inhibit ion–I nt ermit t ent Lp I nhibit ion (I LPI ) or a cont inuat ion
of O O c act ivit y [785] f ollow ing volunt ary closure of t he eyes (pret arsal mot or
persist ence or PMP). The result s f rom t his st udy are as f ollow s:
1. I n some pat ient s, t here may be int ermit t ent involunt ary eye closure as a
result of I LPI . Persist ence of I LPI f ollow ing eye closure w ould int erf ere w it h
eye-opening. When t here is no I LPI , t hese pat ient s have no diff icult y opening
t heir eyes at w ill f ollow ing volunt ary closure.
TABLE 8-14 Etiologies of Apraxia of Eyelid Opening
Extrapyramidal disease
Parkinson's disease
1-methyl-4 phenyl-1,2,3,6 tetrahydropyridine-
induced parkinsonism
Progressive autosomal dominant parkinsonism
and dementia with pallido-ponto-nigral
degeneration
Amyotrophic lateral sclerosis-parkinsonism-
dementia complex
Multiple systems atrophy (e.g., Shy-Drager
syndrome)
Progressive supranuclear palsy
W ilson's disease
Neuroacanthocytosis
Cortical–basal ganglionic degeneration
Adult-onset Hallervordan-Spatz syndrome
Unilateral (especially nondominant hemisphere)
or bilateral hemispheric lesions
Focal inferior and lateral frontal lobe cortical
degeneration
Motor neuron disease
Postbilateral stereotactic subthalamotomy
Postimplantation of bilateral subthalamic nucleus
electrical stimulators for Parkinson's disease
Unilateral putaminal hemorrhage
Isolated finding (may be levodopa-responsive)
2. I n ot her pat ient s, closure of t he eyes due t o I LPI may act ivat e O O c. These
pat ient s have PMP in addit ion t o I LPI and are unable t o open t heir eyes at
w ill f ollow ing volunt ary closure.
3. Pat ient s w ho have PMP alone may be unable t o open t heir eyes at w ill
f ollow ing volunt ary closure. O nce open, t he eyes do not have t he t endency t o
close by t hemselves.
Pt osis may occur on t he side of eye adduct ion (likely due t o paradoxical
supranuclear levat or inhibit ion) w it h Duane's syndrome (see preceding t ext ).
Rarely, mout h opening may be associat ed w it h pt osis (inverse Marcus G unn
phenomenon) due t o synkinesis bet w een t he oculomot or and t rigeminal nerves.
Pt osis may also be psychogenic or f unct ional in nat ure [350] .
Pt osis may also occur w it h lesions of t he ocul omotor nucl eus, f asci cl e, or nerve
and is of t en associat ed w it h ot her signs of oculomot or dysf unct ion (e. g. ,
mydriasis). A pat ient has been described w it h isolat ed, int ermit t ent pt osis as t he
f irst sign of a post erior carot id art ery aneurysm [791] . Lesions of t he CCN cause
bilat eral pt osis [527] . A mild pt osis is also evident w it h ocul osympatheti c l esi ons
(Horner syndrome), in w hich case t here is associat ed miosis. Pt osis may also
occur w it h diseases of t he neuromuscul ar juncti on, such as myast henia gravis,
Lambert –Eat on syndrome [594] , and bot ulism [114] , and w it h myopathi c
processes, such as myot onic muscular dyst rophy, CPEO , and dermat omyosit is.
I nt ermit t ent pt osis w it h diplopia has been described w it h Charcot -Marie-Toot h
disease [729] , and slow ly progressive pt osis may develop in pat ient s w it h
diabet es, perhaps due t o a local myopat hy of t he LP or t arsalis muscles (or
bot h) by chronic local ischemia or hypoxia [73] . I n t he Miller-Fisher variant of
G uillain-Barré syndrome, unilat eral or bilat eral pt osis may occur [79] .
I n myast henia gravis, Cogan's “eyelid t w it ch sign” may be observed. When t he
pat ient is asked t o look up af t er having kept t he eyes direct ed dow nw ard f or 20
t o 30 seconds, t he aff ect ed upper eyelid may t w it ch bef ore set t ing in a pt ot ic
posit ion. Pt osis, w hich may be t emporarily abolished by sust ained upgaze, may
occur w it h t he Lambert -Eat on myast henic syndrome [114, 594] . Pt osis may also
occur as a remot e eff ect of t herapeut ic bot ulinum t oxin B inject ion f or cervical
dyst onia [631] .
Local mechanical f act ors may also cause pt osis, including levat or t endon
damage due t o ocular surgery or t hyroid eye disease. Mechanical causes of
pt osis include t umors or cyst s of t he conjunct iva, inf ect ion (e. g. , presept al or
orbit al cellulit is), cicat ricial scarring (e. g. , post t raumat ic, post surgical, or
post inf lammat ory), inf lammat ion and edema (e. g. , G raves' disease), inf ilt rat ion
(e. g. , amyloid, sarcoid, neoplast ic, Waldenst röm's macroglobulinemia), primary
or met ast at ic t umors or orbit al pseudot umor, cont act lenses w ear, cont act lens
migrat ion, f oreign body react ion, giant papillary conjunct ivit is, and disinsert ion of
t he levat or f rom excessive eyelid manipulat ion [465] . Prolonged hard cont act
lens w ear may induce a low er posit ion of t he upper eyelid and event ually lead t o
pt osis t hrough levat or disinsert ion [800] . Unilat eral isolat ed pt osis has been
described w it h primary orbit al sarcoidosis limit ed t o t he LP superioris muscle
[ 725] . Uddin and Rose described seven cases of dow ngaze “hangup” of t he
upper eyelid w it h biopsy-proved orbit al malignant neoplasms [795] . All seven
pat ient s had pt osis and f our had limit ed elevat ion of t he aff ect ed eye. Keane
described a pat ient w it h a f ixed eyelid w it h f ailure of eyelid relaxat ion and
elevat ion presumed t o be due t o met ast asis f rom breast cancer [402] .
Di si nserti on of the l evator tendon may occur w it h age, result ing in unilat eral or
bilat eral involut ional pt osis in t he elderly. Unlike congenit al pt osis, in w hich t he
dyst rophic levat or precludes normal eyelid excursion, t he lid cont inues t o move
normally in upgaze and dow ngaze in aponeurot ic disinsert ion (excursion of t he
eyelid f rom dow ngaze t o upgaze is usually 9 mm or more). Pt osis must be
diff erent iat ed f rom dermat ochalasis, w hich ref ers t o t he st ret ched, redundant ,
baggy eyelid skin t hat occurs w it h age. Congeni tal ptosi s is usually t he result of
abnormal development of t he levat or and may of t en coexist w it h SR muscle
paresis (bot h muscles originat e f rom a common embryologic t issue mass). Wit h
congenit al pt osis t he levat or is f ibrot ic and dyst rophic, so t hat lid elevat ion in
upgaze is poor (lack of levat or cont ract ion), and t he lid f ails t o f ollow t he globe
in dow ngaze (inabilit y of t he muscle t o relax). Levat or f unct ion (i. e. , excursion of
t he eyelid f rom dow ngaze t o upgaze) is t heref ore poor (5 mm or less).
False pt osis (pseudoptosi s) may occur because of mechanical impairment of
upw ard eyelid movement (e. g. , w it h orbit al t umor), w it h orbit al inf lammat ion and
eyelid sw elling, w it h an anopht halmic socket , w it h micropht halmia or pht hisis
bulbi, w it h lid ret ract ion in t he opposit e eye, and on t he side opposit e a
hypert ropic eye (w hen t he hypert ropic eye f ixes, t he opposit e eye becomes
hypot ropic and demonst rat es an apparent pt osis). Blow s t o t he f orehead,
result ing in orbit al roof f ract ure and subf ront al epidural hemorrhage, may cause
pt osis and ipsilat eral paralysis of globe elevat ion; in t he cont ext of an
ecchymot ic lid, t hese f indings indicat e local damage t o orbit al muscles rat her
t han injury t o t he superior division of t he t hird nerve [414] .
Eyelid Retraction and Lid Lag
The upper lid posit ion is abnormal if it exposes a w hit e band of sclera bet w een
t he lid margin and t he upper corneal limbus. This may be due t o l i d retracti on
(relat ed t o overact ivit y of t he levat or muscle, cont ract ure of t he levat or, or
hyperact ivit y of t he Müller's muscle), w hich may be not ed in t he primary posit ion,
or l i d l ag, w hich is not ed on at t empt ed dow ngaze [66] .
Neurogenic eyelid ret ract ion and lid lag may be due t o supranuclear, nuclear, or
inf ranuclear lesions aff ect ing t he LPS or condit ions t hat produce hyperact ivit y of
t he sympat het ically innervat ed Müller's muscle.
As ment ioned earlier, dorsal mesencephalic supranucl ear lesions may result in
eyelid ret ract ion, w hich is seen w hen t he eyes are in t he primary posit ion of
gaze or on looking upw ard (Col l i er si gn, or “posteri or f ossa stare”). Unlike
t hyroid orbit opat hy, w it h midbrain lesions t here is no ret ract ion in dow ngaze.
Lesions of t he medial or principal port ion (or bot h) of t he NPC are required f or
t he product ion of lid ret ract ion, because t hese st ruct ures are assumed t o be
involved in lid–eye coordinat ion by providing inhibit ory modulat ion of levat or
mot or neuronal act ivit y [692] . Supranuclear periodic eyelid ret ract ion may occur
during seizures and may also signal impending t ent orial herniat ion. Bilat eral
episodic ret ract ion of t he eyelids may occur as a manif est at ion of epilept ic
discharges associat ed w it h pet it mal or myoclonic seizures or due t o “levat or
spasms” during an oculogyric crisis [529] . Lid lag may occur on a supranuclear
basis in PSP, likely due t o def ect ive inhibit ion of t he levat or nuclei during
dow nw ard gaze [249] . Lid lag may occur in G uillain-Barré syndrome (only
observed on dow nw ard gaze) [753] , and lid ret ract ion may also occur w it h
parkinsonism [172] , Fisher syndrome [16] , and PO EMS (peripheral neuropat hy,
organomegaly, endocrinopat hy, M-prot ein, and skin changes–Peripheral
Neuropat hy, O rganomegaly, Endocrinopat hy, M-Prot ein, And Skin Changes)
syndrome [283] .
Lesions of t he medial and/ or principal port ion of t he NPC are essent ial f or t he
product ion of lid ret ract ion because t hese st ruct ures are assumed t o be involved
in lid–eye coordinat ion by providing inhibit ory modulat ion of levat or mot or
neuronal act ivit y [692] . Normally, supranuclear inhibit ion of t he CCN of t he
levat ors releases t he eyelids t o descend w it h t he eyes int o dow ngaze [132] .
Disrupt ed inhibit ion presumably causes eyelid ret ract ion and eyelid lag. Clinical
and experiment al evidence suggest s t hat t here is an inhibit ory premot or net w ork
in t he PAG (t he supraoculomot or area or supra I I I ), dorsal t o t he t hird CN
nucleus, t hat project s f rom t he NPC t o t he cent ral caudal subnucleus [265, 266,
269, 692] . Lesions in t he region of NPC may produce excessive innervat ion t o
t he lids and consequent ly lid ret ract ion in primary posit ion; t heref ore, bilat eral
eyelid ret ract ion and eyelid lag w it h minimal impairment of vert ical gaze has
been described w it h a circumscribed unilat eral lesion immediat ely rost ral and
dorsal t o t he red nucleus involving t he lat eral PAG area in t he region of t he NPC
[ 265, 266, 269] . Eyelid lag w it hout ret ract ion has also been described in
pret ect al disease, implying t hat t hese lid signs may have separat e neural
mechanisms [269] . Conversely, vert ical gaze paralysis w it hout eyelid ret ract ion
may occur; in t hese cases t he f ibers and nucleus of t he PC are spared and t he
lesions are more rost ral, involving t he riMLF, t he I NC, and t he PAG area [692] .
I psilat eral pt osis and cont ralat eral
superior eyelid ret ract ion may be due t o a nuclear oculomot or nerve syndrome
(pl us-mi nus l i d syndrome) [266, 275, 814] . The plus-minus syndrome result s
f rom a unilat eral lesion of t he t hird nerve f ascicle w it h ext ension rost rally and
dorsally t o involve t he nucleus of t he PC or it s connect ions. The plus-minus
syndrome has been described w it h glioma, TNP, orbit al myosit is, myast henia
gravis, congenit al pt osis, and orbit al t rauma [814] . Also, a pat ient has been
described w it h a nuclear TNP, sparing t he caudal cent ral nucleus and it s eff erent
f ibers, w ho had no ipsilat eral pt osis but had cont ralat eral lid ret ract ion [274] .
The cont ralat eral eyelid ret ract ion w as t hought t o be due t o damage t o t he f ibers
f rom t he NPC, most probably in t he region of t he supraoculomot or area, and it is
inf erred f rom t his case t hat inhibit ory connect ions bet w een t he NPC and t he CCN
are unilat eral and crossed. A similar crossed pat t ern may also exist f or
excit at ory aff erent s t o t he CCN as hemispheric lesions result in cont ralat eral
pt osis.
Paroxysmal SR and l evator pal pebrae spasm is a rare and unique disorder
described in a single pat ient w it h mult iple sclerosis [226] . Paroxysms of vert ical
diplopia and lid ret ract ion in t his pat ient last ed 3 t o 4 seconds and examinat ion
revealed int ermit t ent right hypert ropia, lid ret ract ion, and rest rict ion of
dow ngaze. MRI revealed mult iple lesions consist ent w it h mult iple sclerosis,
including a lesion in t he midbrain in t he region of t he t hird nerve f ascicle.
Paradoxic lid ret ract ion may occur w it h jaw movement or sw allow ing (t he Marcus
G unn phenomenon). This t rigemino-oculomot or synkinesis occurs on a congenit al
basis. Eyelid ret ract ion may also occur w it h aberrant regenerat ion of t he
oculomot or nerve (w hen t he eye adduct s), w it h congenit al or acquired abducens
palsies (on abduct ion), w it h levat or denervat ion supersensit ivit y af t er oculomot or
palsies, and w it h irrit at ive oculosympat het ic lesions (Cl aude-Bernard syndrome).
I nt ermit t ent oculosympat het ic irrit at ion may cause cyclic sympat het ic spasm, in
w hich t he pupil dilat es f or 40 t o 60 seconds, w hich may be associat ed w it h lid
ret ract ion, f acial hyperhidrosis, and headache (Cl aude-Bernard syndrome) [128] .
Eyelid ret ract ion may also occur if t here is pt osis of t he opposit e eyelid
(especially w hen t he pt osis is due t o disease at or dist al t o t he neuromuscular
junct ion) w hen f ixat ing w it h t he eye w it h t he unilat eral pt osis (due t o Hering's
law ) [485] . Compensat ory unilat eral O O c cont ract ion may mask lid ret ract ion;
t heref ore, if t he O O c muscle is also w eakened, as in myast henia gravis,
cont ralat eral lid ret ract ion becomes more evident . O t her causes f or lid ret ract ion
include prolonged st eroid use, local applicat ion of phenylephrine, an enlarged
globe, recession of t he SR, or nondyst hyroid cicat ricial ret ract ion (e. g. , due t o
scar af t er t rauma, herpes zost er).
Eyelid ret ract ion and lid lag may also occur w it h neuromuscul ar di seases,
including myast henia gravis, f amilial periodic paralysis, myot onic syndromes, and
t hyroid eye disease [485] .
Myogenic eyelid ret ract ion may also occur af t er bot ulinum t oxin inject ions of t he
eyelids and af t er eye surgery, including SR recession, pt osis repair, and
enucleat ion [66] . Thyroi d eye di sease is one of t he most common et iologies f or
acquired unilat eral or bilat eral sust ained lid ret ract ion; t he ret ract ion is due t o
pat hologic short ening of t he levat or muscle. O n looking dow n, t he eyelid pauses
and t hen f ollow s t he eye (G raef e's si gn) and, in t he primary posit ion, t here is
upper lid ret ract ion w it h inf requent and incomplet e blinking (Stel l wag's si gn).
Upper lid ret ract ion in G raves' disease is likely due t o local adhesions of t he
levat or muscle t o f ixed orbit al t issues; ret ract ion and lag do not correlat e w it h
limit at ion of vert ical eye movement s or I R muscle volume [233] . Bilat eral upper
and low er lid ret ract ion may occur w it h severe liver disease (Summerski l l si gn),
but t he exist ence of t his sign has been quest ioned [67] . Volit ional lid ret ract ion
may occur and is usually bilat eral and associat ed w it h f urrow ing of t he brow s
(f ront alis cont ract ion).
Myast henia gravis may also be associat ed w it h t hree t ypes of eyelid ret ract ion
[ 529] .
1. Pat ient s w it h unilat eral pt osis may develop cont ralat eral eyelid ret ract ion as
t hey at t empt t o elevat e t he pt ot ic lid due t o bilat eral excessive innervat ion t o
t he eyelids.
2. Pat ient s w it h pt osis may develop brief eyelid ret ract ion last ing only seconds
f ollow ing a saccade f rom dow ngaze t o primary posit ion (Cogan's lid t w it ch
sign).
3. Pat ient s may develop t ransient eyelid ret ract ion last ing seconds or minut es
af t er st aring st raight ahead or looking upw ard f or several seconds (possibly
due t o post -t et anic f acilit at ion of t he levat or muscle).
Ret ract ion of t he l ower eyel i d may be t he earliest clinical lid sign of a lesion of
t he f acial nerve, and f acial nerve lesions are t he most common cause of low er lid
ret ract ion [118, 162] . Flaccidit y of t he low er lid may be an early manif est at ion of
f acial muscle paresis in myast henia and myopat hies, and low er lid ret ract ion may
occur w it h propt osis (e. g. , secondary t o t hyroid
orbit opat hy), w it h senile ent ropion or ect ropion, af t er eye muscle or orbit al
surgery, or w it h cont ract ion of lid t issue (e. g. , f rom burns, t umors, or
dermat oses) [162] . Wit h a hypert ropia, t he ipsilat eral lid may appear t o be
ret ract ed, w hereas w it h a hypot ropia, t here may be an illusion of cont ralat eral
lid ret ract ion. Lid ret ract ion may occur w hen t here is elevat ion of t he
cont ralat eral low er eyelid w it h f acial cont ract ure f ollow ing Bell's palsy, spast ic–
paret ic f acial cont ract ure w it h myokymia, hemif acial spasm, enopht halmus, or
Horner syndrome “upside dow n” pt osis.
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> Table of C ontents > C hapter 9 - C r anial Ner ve V ( The Tr igem inal Ner ve)
Chapter 9
Cranial Nerve V (The Trigeminal Nerve)
Anatomy of Cranial Nerve V (Trigeminal Nerve)

The t rigeminal nerve is a mixed nerve t hat provides sensory innervat ion t o t he
f ace and mucous membranes of t he oral and nasal cavit ies and mot or innervat ion
t o t he muscles of mast icat ion [9] .
Motor Portion
The mot or nucleus of t he t rigeminal nerve is sit uat ed at a midpont ine level (Fig.
9-1), medial t o t he main sensory nucleus of t he t rigeminal nerve, near t he f loor
of t he f ourt h vent ricle. I t receives it s supranuclear cont rol t hrough cort icobulbar
f ibers originat ing in t he low er t hird of t he precent ral gyrus. These bilat eral
connect ions t ravel t hrough t he corona radiat a, int ernal capsule, and cerebral
peduncle and decussat e in t he pons bef ore supplying t he mot or nuclei.
The motor root, or port io mi nor, exit s f rom t he mot or nucleus, passes f orw ard in
t he subst ance of t he pons, and emerges f rom t he ant erolat eral aspect of t he
pons ant erior and medial t o t he larger sensory root (t he port io major). The mot or
root t hen passes t hrough t he post erior f ossa and pierces t he dura mat er beneat h
t he at t achment of t he t ent orium t o t he t ip of t he pet rous port ion of t he t emporal
bone. I t t hen ent ers a cavit y in t he dura mat er overlying t he apex of t he pet rous
bone (Meckel 's cave), t ravels beneat h t he tri gemi nal (gasseri an) gangl i a, and
leaves t he skull t hrough t he f oramen oval e. Af t er leaving t he skull, t he mot or
root joins t he mandi bul ar (thi rd) di vi si on of t he t rigeminal nerve t o f orm t he
mandi bul ar nerve, w hich supplies t he mast icat ory muscles: t he masset er,
t emporalis, and medial and lat eral pt erygoid muscles. I n addit ion, mot or f ibers
are given off t o t he t ensor t ympani, t ensor veli palat ini, and mylohyoid muscles,
and t o t he ant erior belly of t he digast ric muscle.
Sensory Portion
The pseudounipolar perikarya of t he sensory port ions of t he t rigeminal nerve are
in t he semi l unar or gasseri an gangl i on, w hich is sit uat ed near t he apex of t he
pet rous bone in t he middle cranial f ossa. From t his ganglion, t he f ibers of t he
sensory root (port io major) ent er t he subst ance of t he pons, course
dorsomedially, and t erminat e in t hree major nuclear complexes (Fig. 9-1) w it hin
t he brainst em: the nucl eus of the spi nal tract of the tri gemi nal nerve, the mai n
(or pri nci pal ) sensory nucl eus, and the mesencephal i c nucl eus.
O n ent ering t he pons, many of t he sensory f ibers descend as a bundle, the
spi nal tract of the tri gemi nal nucl eus, t o t he caudal end of t he medulla and int o
t he spinal cord (as f ar as t he t hird or f ourt h cervical level), w here it becomes
cont inuous w it h Lissauer's t ract . As t he spinal t ract descends, it gives off f ibers
t o t he medially locat ed nucl eus of the spi nal tract of the tri gemi nal nerve, w hich
also descends int o t he upper cervical cord. This nucleus is divided int o a pars
oralis (w hich ext ends f rom t he midpons t o t he inf erior olive), a pars int erpolaris
(w hich ext ends f rom t he rost ral t hird of t he inf erior olive t o t he obex of t he f ourt h
vent ricle), and a pars caudalis (w hich ext ends t o and is cont inuous w it h t he
dorsal horn gray mat t er of t he cervical spinal cord). The f ibers of t he opht halmic
division of t he t rigeminal nerve t ravel in t he most vent ral part of t he spinal t ract
and ext end most caudally (i. e. , t erminat e in t he t rigeminal nucleus in series w it h
t he second cervical sensory level). The f ibers of t he mandibular
division of t he t rigeminal nerve t ravel in t he most dorsal part of t he spinal t ract

and t erminat e in t he most rost ral level of t he spinal nucleus of t he t rigeminal
nerve. The rost ral t rigeminal nuclei are import ant in int raoral and dent al
sensat ion [39] . I n anot her possible sensory somat ot opic spinal nucleus
represent at ion, t he midline f acial areas (nose and mout h) are represent ed
rost rally in t he spinal nucleus, w hereas t he more lat eral f acial sensat ion f ibers
t erminat e in more caudal spinal nucleus regions. This pat t ern of t erminat ion may
account f or t he oni on-ski n pat t ern of f acial sensory loss w it h int ramedullary
lesions and t he perioral numbness t hat occurs w it h more rost ral spinal nucleus
and t ract lesions.
FI G URE 9-1 Schemat ic diagram of t he t rigeminal syst em. CN = cranial nerve.
The spinal nucleus of t he t rigeminal nerve receives f ibers t hat convey t he

sensat ions of pain, t emperat ure, and sof t t ouch f rom t he f ace and mucous
membranes. From t he spinal nucleus, ascending f ibers t ravel mainly ipsilat erally
in t he t rigeminot halamic t ract t o t erminat e in t he vent ral post eromedial–Vent ral
Post eromedial (VPM) and int ralaminar nuclei of t he t halamus.
O t her f ibers f rom t he port io major ent er t he pons and ascend and ent er t he mai n
sensory nucl eus of t he t rigeminal nerve. This nucleus is locat ed in t he lat eral
pons, post erolat eral t o t he mot or nucleus of t he t rigeminal nerve. Fibers ent ering
t his nucleus are concerned w it h t act ile and propriocept ive sensat ion. The main
sensory nucleus gives off ascending f ibers t hat t erminat e in t he t halamus. These
f ibers t ravel in t he ventral crossed tri gemi nothal ami c (qui ntothal ami c) tract or
tri gemi nal l emni scus, w hich ascends w it h t he medial lemniscus, and in t he
uncrossed dorsal tri gemi nothal ami c tract. Bot h t hese f iber t ract s t erminat e
predominant ly in t he VPM nucleus of t he t halamus.
The t hird sensory t rigeminal nucleus, t he mesencephal i c nucl eus, ext ends
cephalad f rom t he main sensory nucleus t o t he superior colliculus of t he
mesencephalon. This nucleus receives propriocept ive impulses f rom t he
mast icat ory muscles and f rom muscles supplied by ot her mot or cranial nerves.
The sensory root (port io major) of t he t rigeminal nerve leaves t he pons along
w it h t he mot or root (port io minor) and expands in t he Meckel's cave t o f orm t he
t rigeminal (gasserian) ganglion. This ganglion lies near t he cavernous sinus and
int ernal carot id art ery and gives rise t o t hree nerve t runks: t he ophthal mi c,
maxi l l ary, and mandi bul ar di vi si ons of the tri gemi nal nerve.
Ophthalmic Division
This division (V1) (Fig. 9-2) lies in t he lat eral w all of t he cavernous si nus in
close associat ion w it h t he t hird, f ourt h, and sixt h cranial nerves. Along w it h t hese
t hree nerves, t he opht halmic division ent ers t he orbit t hrough t he superi or orbi tal
f i ssure. Bef ore leaving t he cavernous sinus, t his division divides int o t ent orial,
lacrimal, f ront al, and nasociliary branches. The tentori al branch supplies t he
dura of t he cavernous sinus, sphenoid
w ing, ant erior f ossa, pet rous ridge, Meckel's cave, t ent orium cerebelli, post erior
f alx cerebri, and dural venous sinuses. The f rontal branch divides int o t he
supraorbi tal nerve—supplying t he medial upper lid and conjunct iva, t he f ront al
sinuses, t he f orehead, and t he scalp—and t he supratrochl ear nerve, w hich
supplies t he conjunct iva, medial upper lid, f orehead, and side of nose (Fig. 9-3).
The l acri mal nerve, t hrough it s lat eral palpebral branch, innervat es t he
conjunct iva and skin in t he area of t he lacrimal gland. The lacrimal nerve also
carries post ganglionic parasympat het ic f ibers f or ref lex lacrimat ion. The
nasoci l i ary nerve divides int o nasal nerves, w hich innervat e t he mucosa of
t he nasal sept um, t he lat eral nasal w all, and t he inf erior and middle t urbinat es,
and an ext ernal nasal branch, w hich innervat es t he skin of t he t op of t he nose.
The inf rat rochlear branch of t he nasociliary nerve supplies t he lacrimal sac, t he
caruncle, and t he conjunct iva and skin of t he medial cant hus. Tw o long ciliary
nerves carry sensat ion f rom t he ciliary body, t he iris, and t he cornea and also
carry sympat het ic innervat ion t o t he dilat or of t he pupil. Mult iple short ciliary
nerves t ransmit sensory f ibers f rom t he globe, w hich pass t hrough t he ciliary
ganglion t o join t he nasociliary nerve; t hese short ciliary nerves also carry
post ganglionic parasympat het ic f ibers f rom t he ciliary ganglion t o t he const rict or
of t he pupil and t he ciliary muscle. The parasympat het ic f ibers reach t he ciliary
ganglion t hrough t he inf erior division of t he oculomot or nerve dest ined t o
innervat e t he inf erior oblique muscle.
FI G URE 9-2 The branches of t he opht halmic and maxillary divisions of t he

t rigeminal nerve.
FI G URE 9-3 Areas of skin supplied by t he t hree major t rigeminal nerve
divisions.
The opht halmic division t heref ore supplies t he skin of t he nose, t he upper eyelid,
t he f orehead, and scalp (as f ar back as t he lambdoidal sut ure in t he midline and
f or 8 cm lat eral t o t he midline) (Fig. 9-3); t he upper half of t he cornea,
conjunct iva, and iris; t he mucous membranes of t he f ront al, sphenoidal, and
et hmoidal sinuses and t he upper nasal cavit y and sept um; t he lacrimal canals;
and t he dura mat er of t he ant erior cranial f ossa, f alx cerebri, and t ent orium
cerebelli.
M axillary Division
This division (V2) passes (Figs. 9-2 and 9-4) t hrough t he inf erolat eral port ion of
t he cavernous si nus and t hen leaves t he skull t hrough t he f oramen rot undum t o
ent er t he sphenopal ati ne f ossa. Next , it ent ers t he orbit t hrough t he inf erior
orbit al f issure (as t he i nf raorbi tal nerve) and, af t er t raveling t hrough t he
inf raorbit al canal, reaches t he f ace by w ay of t he i nf raorbi tal f oramen. Wit hin
t he sphenopalat ine f ossa and inf raorbit al canal, pal ati ne nerves and mi ddl e,
posteri or, and anteri or superi or al veol ar nerves arise, w hich supply t he upper
t eet h, maxillary sinus, nasopharynx, sof t palat e, roof of t he mout h, and t onsils.
Af t er exit ing f rom t he inf raorbit al f oramen, t he nerve divides int o an i nf eri or
pal pebral branch t o t he low er lid, a nasal branch t o t he side of t he nose, and a
superi or l abi al branch t o t he upper lip. A zygomati cof aci al branch innervat es t he
cheek.
FI G URE 9-4 The branches of t he maxillary division of t he t rigeminal nerve.
The maxillary division t heref ore supplies t he skin of t he low er eyelid, t he lat eral
nose, upper lip, and cheek (Fig. 9-3); t he low er half of t he cornea, conjunct iva,
and iris; t he mucous membranes of t he maxillary sinus, low er nasal cavit y, hard
and sof t palat es, and upper gum; t he t eet h of t he upper jaw ; and t he dura mat er
of t he middle cranial f ossa (t hrough t he middle or recurrent meningeal nerve).
M andibular Division
The mandibular division (V3) (Fig. 9-5) joins t he mot or root of t he t rigeminal
nerve t o f orm t he mandi bul ar nerve. This nerve leaves t he skull t hrough t he
f oramen oval e and t ravels in t he inf rat emporal f ossa, dividing f inally int o several
t erminal branches. The motor branches suppl y t he eight muscles not ed in t he
preceding t ext , w hereas t he l i ngual nerve conveys sensat ion f rom t he low er
gums
and t he papillae and mucous membrane of t he ant erior t w o-t hirds of t he t ongue.
Inf eri or dental branches suppl y t he low er gums and t eet h of t he mandible;
mental branches, af t er emerging f rom t he bone at t he ment al f oramen, supply
t he skin of t he chin and t he skin and mucous membrane of t he low er lip.
FI G URE 9-5 The branches of t he mandibular division of t he t rigeminal nerve.
I n addit ion t o t he muscles list ed previously (see Mot or Port ion), t he mandibular
nerve supplies t he skin of t he low er lip, low er jaw, chin, t ympanic membrane,
audit ory meat us, and upper ear (Fig. 9-3); t he mucous membranes of t he f loor of
t he mout h, t he low er gums, and t he ant erior t w o-t hirds of t he t ongue (not t ast e
sensat ion, w hich is carried by t he f acial nerve); t he t eet h of t he low er jaw ; and
t he dura mat er of t he post erior cranial f ossa.
Clinical Evaluation of Cranial Nerve V Function

Sensory Evaluation
Ext erocept ive sensat ion (pain, light , t ouch, heat , and cold) is t est ed on t he f ace
and mucous membranes. Each of t he t hree t rigeminal divisions is t est ed
individually and compared w it h t he opposit e side. Lesions of individual divisions
(dist al t o t he gasserian ganglion) result in sensory loss conf ined t o t he
cut aneous supply of t hat division (Fig. 9-3) w it h relat ively lit t le overlap int o t he
cut aneous area of anot her division. Lesions at or proximal t o t he gasserian
ganglion result in sensory loss t hat aff ect s t he w hole ipsilat eral f ace. Lesions
w it hin t he brainst em or upper cervical cord may result in an onion-skin
dist ribut ion of sensory loss, w hereas dissociat ion of sensat ion on t he f ace (pain
and t emperat ure vs. t ouch sensat ion) diff erent iat es lesions aff ect ing t he spinal
t ract and nucleus of t he t rigeminal nerve f rom lesions aff ect ing t he main sensory
nucleus.
The cut aneous area over t he angle of t he mandible is supplied by t he second and
t hird cervical root s (by w ay of t he great auricular nerve) and not by t he
t rigeminal nerve. Theref ore, a hemif acial sensory loss t hat spares t he angle of
t he jaw is probably organic, w hereas one t hat includes t his area may be of
f unct ional origin or relat ed t o an int ramedullary lesion.
Motor Evaluation
The t rigeminal nerve supplies t he muscles of mast icat ion. These are t est ed by
having t he pat ient clench t he jaw (masset ers and t emporalis), move
t he jaw f rom side t o side against resist ance (lat eral pt erygoids), and prot rude
t he jaw. Wit h nuclear or inf ranuclear lesions of t he mot or division of t he
t rigeminal nerve, t he t emporalis and masset er muscles on t he side of t he lesion
do not cont ract w hen t he jaw is clenched, t he jaw deviat es t o t he paralyzed side
w hen t he mout h is opened (due t o cont ract ion of t he cont ralat eral int act lat eral
pt erygoid muscle), and t he jaw cannot be deviat ed t ow ard t he nonparalyzed side
(due t o ipsilat eral lat eral pt erygoid paresis). At rophy and f asciculat ion of t he
mast icat ory muscles may also be evident . Trismus (inabilit y t o open t he jaw ) may
be seen w it h acut e dyst onic react ions, polymyosit is, t et anus, t rauma t o t he
muscles of mast icat ion, inf ect ion of t he pt erygomandibular space, t rypt ophan-
associat ed eosinophilic connect ive t issue disease, nemaline myopat hy, and
psychogenic f act ors [15, 74, 88] .
O t her muscles supplied by t he t rigeminal nerve (mylohyoid, ant erior belly of t he
digast ric, t ensor, t ympani, t ensor veli palat ini) are diff icult t o evaluat e clinically.
How ever, f laccidit y of t he f loor of t he mout h due t o mylohyoid and digast ric
paralysis may be evident on palpat ion, and paralysis of t he t ensor t ympani may
result in diff icult y in hearing high not es.
Reflex Evaluation
The import ant ref lexes conveyed by t he t rigeminal nerve include t he corneal
ref lex and t he jaw jerk (masset er ref lex). The aff erent arc of t he corneal ref l ex
t ravels t hrough t he opht halmic (upper cornea) and maxillary (low er cornea)
divisions of t he t rigeminal nerve. The eff erent arc moves t hrough t he ipsilat eral
(direct ref lex) and cont ralat eral (consensual ref lex) f acial nerve t o t he orbicularis
oculi muscles. Lesions of t he t rigeminal nerve result in loss of t he ipsilat eral and
cont ralat eral responses. These lesions may involve t he peripheral or
pont omedullary t rigeminal pat hw ays; how ever, a suprasegment al modulat ion of
t his ref lex also exist s, because a pariet al lobe lesion (involving t he perisylvian
port ion of t he post cent ral gyrus) may result in a cont ralat eral loss of t he corneal
ref lex. The jaw jerk or masseter ref l ex involves cont ract ion of t he masset er and
t emporalis muscles w hen t he pat ient 's low er jaw is t apped. The aff erent arc is
t hrough t he 1a mot or f ibers in t he mandibular division of t he t rigeminal nerve t hat
run t o t he mesencephalic nucleus of t he t rigeminal nerve. The eff erent arc also
t ravels t hrough mandibular f ibers t hat originat e in t he mot or nucleus of t he
t rigeminal nerve. Lesions anyw here along t his ref lex arc result in depression of
t he ipsilat eral jaw ref lex, w hereas bilat eral supranuclear lesions result in an
accent uat ed response.
Trigeminal sensory neuropat hy may result in signif icant disabilit y due t o impaired
int raoral sensat ion associat ed w it h a dist urbance of mast icat ion and sw allow ing
[ 3] . Dist urbed int raoral sensat ion, combined w it h impaired t rigeminal ref lexes
(especially t he masset er inhibit ory ref lex), int erf eres w it h t he neural mechanisms
t hat regulat e chew ing.
Anot her ref lex mediat ed part ly by t rigeminal pat hw ays is t he bl i nk ref l ex
(glabellar ref lex, orbicularis oculi ref lex). Percussion over t he supraorbit al ridge
result s in bilat eral cont ract ion of t he orbicularis oculi muscles. The aff erent arc
of t his response is likely mediat ed by t he ipsilat eral main sensory nucleus of t he
t rigeminal nerve and t he ipsilat eral and cont ralat eral spinal nuclei of t he
t rigeminal nerve. The spinal nuclei of t he t rigeminal nerve (bilat eral) make mot or
connect ions t hrough t he corresponding f acial nuclei, w hich innervat e t he
orbicularis oculi muscles. By st udying t he blink ref lex elect rically, subt le
peripheral and cent ral lesions of t he t rigeminal and f acial nerves may be
uncovered.
The corneomandi bul ar ref l ex consist s of bilat eral eye blink and a brisk
ant erolat eral jaw movement induced by corneal st imulat ion [75] . A spont aneous
pal pebromandi bul ar (eyel i d jaw) synki nesi a–Spont aneous Pal pebromandi bul ar
(Eyel i d Jaw) Synki nesi a ( SPMS), in w hich jaw movement s similar t o t hose in t he
corneomandibular ref lex regularly accompany spont aneous eye blinks w it hout an
ext ernal corneal st imulat ion, has been described in pat ient s w it h upper brainst em
(bilat eral lesions above t he midpons) or bilat eral cerebral lesions [75] . SPMS is
pat hophysiologically t he same as t he eyelid jaw synkinesia of t he
corneomandibular ref lex, and bot h synkinesias originat e cent rally, probably in t he
pons. I n t he corneomandibular ref lex, t he jaw movement is primarily relat ed t o
t he blink rat her t han t he corneal st imulus, but corneal st imulat ion may be
necessary t o overcome a higher t hreshold f or expression of t he synkinesia in
pat ient s w it h SPMS [75] .
Localization of Lesions Affecting Cranial Nerve V

Supranuclear Lesions
Supranuclear cont rol of t rigeminal mot or f unct ion is bilat eral; how ever, t he
cont ralat eral hemisphere exert s predominant cont rol on t he volunt ary act ivit y of
t he masset er [18] . Cort icobulbar f ibers originat e in t he low er f ront al mot or
cort ex, descend t hrough t he corona radiat a, int ernal capsule, and cerebral
peduncle, and t hen decussat e in t he pons
t o supply t he mot or nucleus of t he t rigeminal nerve. Lesions int errupt ing t his
pat hw ay may result in cont ralat eral t rigeminal mot or paresis (e. g. , deviat ion of
t he jaw “aw ay f rom” t he lesion), but because of t he bilat eral innervat ion, paresis
may be mild. Bilat eral upper mot or neuron lesions (pseudobulbar palsy) result in
prof ound t rigeminal mot or paresis, of t en w it h an exaggerat ed jaw ref lex.
Mast icat ion is t hen markedly impaired. Thalamic lesions may result in anest hesia
of t he cont ralat eral f ace. Pariet al lesions may be associat ed w it h depression of
t he cont ralat eral corneal ref lex, even w hen f acial sensat ion is ot herw ise int act .
Nuclear Lesions
The mot or and sensory nuclei of t he t rigeminal nerve may be involved by lesions
(e. g. , primary or met ast at ic t umors, art eriovenous malf ormat ion, demyelinat ing
disease, inf arct ion, hemorrhage, syringobulbia) t hat aff ect t he pons, medulla, or
upper cervical cord. These nuclear lesions involve ot her brainst em st ruct ures,
and t heref ore brainst em lesions of t he t rigeminal nuclei are diagnosed by “t he
company t hey keep” (e. g. , long t ract signs, and ot her cranial nerve involvement ).
Lesions aff ect ing t he dorsal midpons may aff ect t he motor nucl eus of the
tri gemi nal nerve. Congenit al anomalies of t he mot or component of t he t rigeminal
nerve are rare, and may be associat ed w it h t he involvement of cranial nerve VI I
or XI I . I psilat eral paresis, at rophy, and f asciculat ions of t he muscles of
mast icat ion t heref ore occur. A pont ine localizat ion of t his mast icat ory paresis is
suggest ed by associat ed f indings t hat may include cont ralat eral hemiplegia (due
t o aff ect ion of t he basis pont is), ipsilat eral hemianest hesia of t he f ace (due t o
aff ect ion of t he main sensory nucleus of t he t rigeminal nerve), cont ralat eral
hemisensory loss of t he limbs and t runk (due t o spinot halamic t ract aff ect ion),
and ipsilat eral t remor (due t o aff ect ion of t he brachium conjunct ivum).
I nt ernuclear opht halmoplegia (secondary t o medial longit udinal f asciculus
damage) and an ipsilat eral Horner syndrome (due t o involvement of descending
sympat het ic f ibers) may also occur. Pont ine syndromes are more t horoughly
discussed in Chapt er 15. Lat eral pont ine t egment al hemorrhage may rarely
present as an isolat ed t rigeminal sensory neuropat hy, w it h numbness and
parest hesias of half of t he f ace, scalp, ear, and t ongue [45] , perhaps due t o t he
involvement of t he main sensory nucleus of t he t rigeminal nerve. A pat ient w it h
small lef t dorsolat eral pont ine inf arct present ed w it h isolat ed orof acial sensory
def icit s (lef t upper f ace, t ongue, and buccal mucosa numbness and parest hesias)
w it hout t runk or limb sensory f indings indicat ing exclusive involvement of t he
pont ine t rigeminal sensory complex, including t he principle sensory nucleus and
t he pars oralis of t he spinal t rigeminal nucleus and t ract [47] . Unilat eral
t rigeminal pain and numbness in a V1 t hrough V3 dist ribut ion w it h decreased
corneal ref lex has also been described w it h a pont ine abscess [5] .
Pat ient s w it h dorsal pont ine lesions (usually t umors) may develop unilat eral
spasm and cont ract ure of t he masset er muscle, impairing t he abilit y t o open t he
jaw and f orcing t he pat ient t o “speak t hrough t he t eet h” [90] . Hemi masti catory
spasm is a rare disorder of t he t rigeminal nerve t hat involves one or more of t he
jaw -closing muscles (masset er, t emporalis, and medial pt erygoid) on one side of
t he f ace and produces involunt ary jaw closure due t o paroxysmal unilat eral
muscle cont ract ion [2, 19, 29, 50, 72, 93] . The spasms may be sudden and brief
or may last several minut es and cause int ense pain. They are of t en t riggered by
volunt ary jaw closure or ot her movement s of t he jaw and are somet imes relieved
by volunt ary jaw opening. Trigeminal f unct ion is ot herw ise normal.
Elect rophysiologic f indings in hemimast icat ory spasm suggest ect opic excit at ion
of t he t rigeminal mot or root or it s nucleus, an abnormalit y t hat is analogous t o
ect opic excit at ion of t he f acial nerve in hemif acial spasm [2, 19] . Some aut hors
suggest t hat t he nerve t o t he masset er and t emporalis muscles may be
ent rapped at a point in it s course bet w een t he lat eral pt erygoid muscle and t he
skull causing f ocal demyelinat ion and spont aneous discharges [19] .
Hemimast icat ory spasm may be associat ed w it h localized scleroderma [52] or
may be seen w it h f acial hemiat rophy [19, 29, 50, 52, 72, 93] .
The nucl eus of the spi nal tract of the tri gemi nal nerve ext ends f rom t he caudal
end of t he pons t o t he t hird or f ourt h cervical spinal cord level. Theref ore,
lesions aff ect ing t he caudal pons, lat eral medulla, or upper cervical cord result in
ipsilat eral f acial analgesia, hypest hesia, and t hermoanest hesia. Because t he
lat eral spinot halamic t ract lies in close proximit y t o t he t rigeminal spinal nucleus,
t he hemif acial sensory dist urbance is of t en associat ed w it h cont ralat eral t runk
and ext remit y hypalgesia and t hermoanest hesia. How ever, isolat ed orof acial pain
and sensory def icit over t he ipsilat eral f ace, neck, t ongue, and oral cavit y may
occur w it h small pont ine or medullary lesions [45, 70] . Caudal pont ine lesions
may damage t he rost ral spinal t rigeminal nuclei and result in diminished i ntraoral
sensat ion f or all modalit ies but spared f acial sensat ion [16, 39] .
Pat ient s w it h isolat ed vent ral pont ine inf arct ion may present w it h prominent
ipsilat eral midf acial sensory signs (hypest hesia and numbness of t he midline
f acial areas) associat ed w it h dysart hria and cont ralat eral hemiparesis [64] . The
clinicoanat omic basis of t he ipsilat eral midf acial sensory loss is unknow n but
may be t hrough t he involvement of t he dorsal t rigeminot halamic t ract or f ibers
relat ed t o t he cent ral regions of t he f ace locat ed medially. Wit h upper (rost ral)
medullary spinal nuclear lesions, t he ent ire t rigeminal cut aneous dist ribut ion is
aff ect ed. Low er medullary or upper cervical spinal nuclear lesions result in a
sensory dist urbance t hat aff ect s t he peripheral (lat eral) f orehead, cheek, and
jaw (onion-skin pat t ern of sensory loss). This onion-skin segment al dist ribut ion
ref lect s t he rost ral–caudal somat ot opic arrangement of t he cut aneous
dist ribut ion of t he spinal nucleus (e. g. , perioral area—rost ral; lat eral f ace—
caudal).
The spinal nucleus of t he t rigeminal nerve is charact erist ically aff ect ed in t he
l ateral medul l ary (Wal l enberg) syndrome, w hich is most of t en secondary t o
brainst em inf arct ion due t o int racranial vert ebral art ery occlusion [54, 55] . This
syndrome is described in Chapt er 5. Currier et al. divided t he t rigeminal sensory
loss in pat ient s w it h Wallenberg syndrome int o f our clinical groups [21] :
1. I n t he t ypical syndrome, pain and t emperat ure sensat ion are lost over t he
ent ire side of t he f ace.
2. I n t he vent ral syndrome, t he f irst and second divisions of t he t rigeminal area
are involved. This dist ribut ion f ollow s damage t o t he vent ral aspect of t he
descending t ract and nucleus of V, w here t he opht halmic and maxillary f ibers
t ravel.
3. I n t he dorsolat eral syndrome, only t he second and t hird divisions of t he
descending t ract are aff ect ed.
4. I n t he superf icial syndrome, all port ions of t he ipsilat eral f ace are involved
init ially, but sympt oms are mild and improve rapidly.
I n a st udy by Kim et al. of 50 pat ient s w it h sensory dysf unct ion f rom lat eral
medullary inf arct ion [55] , t he f indings w ere as f ollow s:
1. Thirt een pat ient s (26%) had a “classic” ipsilat eral t rigeminal–cont ralat eral
body and limb pat t ern of sensory loss w it h lesions aff ect ing t he most
post erolat eral part of t he caudal-middle medulla.
2. Tw elve pat ient s had a bilat eral t rigeminal pat t ern associat ed w it h large
vent rally ext ending lesions usually at t he middle-rost ral medulla.
3. Nine pat ient s had a cont ralat eral t rigeminal pat t ern w it h lesions sparing t he
most post erolat eral area of t he medulla.
4. Ten pat ient s had isolat ed body and limb sensory involvement .
5. Four pat ient s had isolat ed t rigeminal involvement .
6. Tw o pat ient s had no sensory signs.
I n t hese pat ient s, t rigeminal sensat ion w as usually inhomogeneously involved

among t he t hree t rigeminal divisions and w as more of t en of an onion-skin pat t ern
t han a divisional pat t ern. Theref ore, in t his st udy, t he so-called cl assi c
dissociat ed sensory pat t ern of lat eral medullary inf arct ion w as act ually
uncommon, w hereas sensory pat t erns previously t hought of as at ypical w ere
relat ively f requent [55] . Pat ient s w it h cont ralat eral f ace-arm-t runk-leg sensory
loss w it h lat eral medullary inf arct ion of t en have ret ro-olivary lesions in t he
vent rolat eral t egment um w it h preservat ion of t he lat eral medulla [95] . The
mediolat eral lesion in t hese pat ient s likely involves t he crossed lat eral
spinot halamic t ract and t he vent ral t rigeminot halamic t ract , corresponding t o t he
cont ralat eral arm, f ace, and leg sensory loss. The vent rolat eral ext ension of t he
inf arct damages t he f ar lat eral part of t he spinot halamic t ract , corresponding t o
sensory loss in t he cont ralat eral low er t runk and leg [95] . Pat ient s w it h lat eral
medullary inf arct ion may develop diminished f acial pain and t emperat ure
sensat ion, sparing int raoral st ruct ures (because t he rost ral spinal t rigeminal
nuclei in t he caudal half of t he pons conveying int raoral sensat ion is spared)
[ 39] .
The sensory sequelae in pat ient s w it h lat eral medullary inf arct s include f acial
numbness, burning, or coldness; t hese sensory sympt oms are of t en of delayed
onset (up t o 6 mont hs af t er t he inf arct ) [51] . Also, rare pat ient s w it h Wallenberg
syndrome may develop neurot rophic ulcerat ions in t he t errit ory of t he t rigeminal
nerve [28, 44] . Such ulcerat ions have also been described f ollow ing alcohol
inject ion of t he gasserian ganglion, post encephalit ic parkinsonism, syringobulbia,
and t rigeminal rhizot omy [28, 44] .
Lesions aff ect ing t he mesencephal i c nucl eus of the tri gemi nal nerve cause no
apparent neurologic signs and sympt oms, except perhaps depression of t he
ipsilat eral jaw jerk (masset er ref lex).
Lesions Affecting the Preganglionic Trigeminal Nerve

Roots
I n it s cist ernal course, t he preganglionic t rigeminal nerve root may be damaged
by t umor (meningioma,
schw annoma, met ast asis, nasopharyngeal carcinoma), inf ect ion (granulomat ous,
inf ect ious, or carcinomat ous meningit is), t rauma, or aneurysm. Preganglionic
t rigeminal nerve involvement is suggest ed by t he involvement of t he neighboring
cranial nerves (especially cranial nerves VI , VI I , and VI I I ). Trigeminal damage is
manif est ed by ipsilat eral f acial pain, parest hesias, numbness, and sensory loss.
The corneal ref lex is depressed and a t rigeminal mot or paresis may occur. An
idiopat hic, isolat ed, self -limit ed t rigeminal sensory neuropat hy w it h t ransient
abnormalit ies on magnet ic resonance imaging–Magnet ic Resonance I maging
(MRI ) has been described [79] . Some pat ient s w it h “idiopat hic” t rigeminal
neuralgia have enhancement of t he cist ernal segment of t he t rigeminal nerve on
MRI st udies [87] . This enhancement usually resolves if t he pain resolves.
The t rigeminal root s may be involved by ext ension of pat hologic processes
(usually acoust ic neuroma or meningioma) locat ed in t he cerebellopont ine angle.
I psilat eral f acial pain, parest hesias, sensory loss, mast icat ory paresis, and a
depressed corneal ref lex are t hen associat ed w it h ipsilat eral t innit us, deaf ness,
and vert igo (due t o involvement of cranial nerve VI I I ). Facial nerve paralysis,
ipsilat eral at axia, and nyst agmus (due t o involvement of t he cerebellar peduncles
and cerebellum), ipsilat eral lat eral rect us paralysis (due t o abducens nerve
involvement ), and, rarely, aff ect ion of cranial nerves I X t hrough XI I may also
occur.
Tri gemi nal neural gi a (ti c doul oureux, Fothergi l l 's di sease) ref ers t o a dist inct ive
syndrome of sudden, excruciat ing, lancinat ing, paroxysmal, and usually unilat eral
pains in t he dist ribut ion of one or more of t he divisions (of t en t he maxillary or
mandibular) of t he t rigeminal nerve [35] . This syndrome is more common w it h
advancing age, aff ect s w omen more of t en t han men, and aff ect s t he right side
more t han t he lef t . I t is exceedingly rare f or a pat ient t o have bilat eral t rigeminal
neuralgia during t he same period of t ime, except in cases of mult iple sclerosis.
Typically, t he paroxysms of pain are brief , usually last ing less t han a minut e. I n
severe cases, t he pain may recur several t imes a day. The at t acks are most
f requent during t he day, but t hey may aw aken t he pat ient at night . The painf ul
paroxysms are of t en t riggered by non-nocicept ive f acial st imulat ion and are of t en
associat ed w it h f acial cont ort ions. Pain arising f rom t he maxillary division (V2) is
of t en ref erred t o t he upper lip, nose, and cheek. Pain originat ing in t he
mandibular division (V3) is of t en ref erred t o t he low er lip. Tic pain conf ined t o
t he opht halmic division (V1) is dist inct ly uncommon. Alt hough of t en called
idiopat hic, t his painf ul f acial syndrome may be seen w it h pat hology aff ect ing t he
brainst em, preganglionic root , gasserian ganglion, and peripheral t rigeminal
nerve [25] . Many cases are probably due t o compression or irrit at ion of t he
ent ry zone of t he t rigeminal nerve root (e. g. , by a mult iple sclerosis plaque,
brainst em inf arct ion, cerebellopont ine angle t umor, cavernous malf ormat ion, or
an aberrant blood vessel, most f requent ly t he superior cerebellar art ery) [24, 36,
43, 48, 53, 66, 82] . Among 2, 972 pat ient s w it h t rigeminal neuralgia in one
series, 296 had t umors causing t he f acial pain [14] . The pat ient s w it h t umors
causing t rigeminal neuralgia w ere younger t han t he pat ient s w it h idiopat hic pain,
but gender and pain dist ribut ions w ere similar. Meningiomas and post erior f ossa
t umors w ere t he most common t umors causing t rigeminal pain [14] . Dist ort ion of
t he t rigeminal sensory root secondary t o brainst em displacement may cause
t rigeminal neuralgia in pat ient s w it h Chiari's malf ormat ion or basilar invaginat ion
(e. g. , due t o ost eogenesis imperf ect a) [76] . How ever, a pat ient w it h a Chiari's
t ype I malf ormat ion present ed w it h t rigeminal neuralgia t hought t o be because of
compression of t he t rigeminal nucleus [80] . Trigeminal neuralgia ow ing t o pont ine
inf arct ion, w it h t he lesion t ransect ing t he cent ral t rigeminal pat hw ays, has also
been described [73] .
I n some pat ient s w it h mult iple sclerosis, t rigeminal neuralgia paroxysms may be
t riggered by audit ory st imuli [43] . Lesions in t hese pat ient s w ere in t he pons
aff ect ing t he ipsilat eral lat eral lemniscus and t rigeminal pat hw ay. The lat eral
spread of t he impulse w it hin t he demyelinat ing pont ine lesion is t he likely
explanat ion f or t his phenomenon.
O ccasionally, pat ient s w ho are dest ined event ually t o develop t rigeminal
neuralgia may have prodromal pain of t oot hache or sinusit is charact er last ing up
t o several hours (pretri gemi nal neural gi a) [32] . This pain may be t riggered by
jaw movement s or by drinking hot or cold liquids; t ypical t rigeminal neuralgia
t hen develops days (or even years) lat er in t he same dist ribut ion.
Lesions Affecting the Gasserian Ganglion

Lesions of t he middle cranial f ossa (e. g. , t umor, herpes zost er, sarcoidosis,
syphilis, t uberculosis, arachnoidit is, t rauma, abscess) may direct ly damage t he
gasserian ganglion in Meckel's cave [20] . Pain, of t en severe and paroxysmal, is
t he most charact erist ic f inding and may be hemif acial or involve only select
divisions of t he t rigeminal nerve (especially t he maxillary and mandibular
divisions). Parest hesias and numbness may also
occur, of t en st art ing close t o t he midline on t he upper lip and chin and
progressing lat erally t o involve t he ant erior ear. Sensory loss occurs in t he
division or divisions aff ect ed, and unilat eral pt erygoid and masset er paresis may
occur. O t her cranial nerves (especially t he abducens nerve) may also be
aff ect ed. Vascular compromise of t he ganglion, causing isolat ed f acial
numbness, has been described w it h a spont aneous dural ext ernal carot id-
cavernous sinus f ist ula [77] . Mult iple cranial neuropat hies, including variable
aff ect ion of t he t rigeminal divisions, may occur w it h primary amyloidosis [94] ,
and bilat eral t rigeminal neuropat hies associat ed w it h bilat eral abducens nerve
palsies has been described w it h Tangier disease [12] .
A unilat eral or bilat eral t rigeminal sensory neuropat hy may be seen w it h gren's
syndrome Sjögren's syndrome, rheumat oid art hrit is, syst emic sclerosis, mixed
connect ive t issue disease, syst emic lupus eryt hemat osus, Churg-St rauss
syndrome, and dermat omyosit is [30, 42, 59, 86] . Facial numbness w it h or
w it hout parest hesias, of t en associat ed w it h f acial pain, is most of t en seen in a
maxillary dist ribut ion. O ccasionally, sympt oms are bilat eral. The t rigeminal
sympt oms develop bef ore sympt oms of t he connect ive t issue disease in 7% and
concurrent w it h t he sympt oms of connect ive t issue disease in 47% [42] .
Numbness, of t en associat ed w it h f acial pain, is most of t en not ed in a maxillary
dist ribut ion; oropharyngeal involvement may be prominent , and occasionally
sympt oms may be bilat eral. Trigeminal sensory neuropat hy may be dist inguished
f rom ot her condit ions associat ed w it h f acial numbness by it s sparing of t he
muscles of mast icat ion, f requent bilat eralit y, occasional disregard f or t rigeminal
boundaries, and negat ive neuroimaging st udies. Half of t he pat ient s complain of
alt ered or absent t ast e, but w hen t est ed, primary gust at ory sensibilit y is
present . The lesion is suspect ed t o involve t he t rigeminal ganglion or proximal
part of t he main t rigeminal divisions and is perhaps relat ed t o t he capillaries of
t he t rigeminal ganglion being more permeable t han t he brain capillaries (blood–
brain barrier) t o abnormal prot eins [59] .
Trigeminal injury may occur w it h penet rat ing or blunt head t rauma [49] . For
example, a blow t o t he auriculot emporal area may rarely cause an i sol ated,
complet e sensory and mot or t rigeminal neuropat hy [84] .
Raeder's Paratrigeminal Syndrome

This syndrome is composed of t w o essent ial component s: unilat eral
oculosympat het ic paresis and evidence of t rigeminal involvement on t he same
side [68] . The f ormer consist s of miosis and pt osis but diff ers f rom t he t ypical
Horner syndrome in t hat f acial anhidrosis is absent because t he sudomot or f ibers
t o t he f ace t hat t ravel ext racranially w it h t he ext ernal carot id art ery are spared.
The unilat eral head, f acial, or ret ro-orbit al pain relat ed t o t rigeminal dysf unct ion
may be associat ed w it h evidence of involvement of ot her cranial nerves (e. g. ,
cranial nerves I V and VI ). This syndrome is usually due t o lesions in t he middle
cranial f ossa, especially in t he region bet w een t he t rigeminal ganglion and t he
int ernal carot id art ery, near t he pet rous apex. I t may also be caused by lesions
of t he gasserian ganglion. The usual et iologies include t umor, aneurysm, t rauma,
and inf ect ion.
Gradenigo's Syndrome
Lesions locat ed at t he apex of t he t emporal bone, especially met ast asis,
ost eit is, or lept omeningit is associat ed w it h ot it is media, may cause damage t o
t he opht halmic division of t he t rigeminal nerve and t he nearby abducens nerve
(G radeni go's syndrome) [23] . Pain and sensory dist urbance in t he upper part of
t he f ace (opht halmic dist ribut ion) are t hen associat ed w it h ipsilat eral lat eral
rect us palsy. O culosympat het ic paresis (w it hout anhidrosis) may also occur
ipsilat erally if t he lesions ext end t o involve sympat het ic f ibers. O t her et iologies
f or t his syndrome include t rauma and t umor.
The Cavernous Sinus Syndrome

Lesions w it hin t he cavernous sinus (e. g. , t umor, carot id aneurysm, t rauma,
carot id-cavernous f ist ula, inf ect ion) may damage t he opht halmic and maxillary
divisions of t he t rigeminal nerve and t he abducens, t rochlear, and oculomot or
nerves. Tot al unilat eral opht halmoplegia, usually st art ing w it h abducens nerve
involvement , if t he lesion originat es lat erally, or oculomot or palsy, if t he lesion
proceeds f rom t he sella, is t hen associat ed w it h pain, parest hesias, and sensory
loss in t he dist ribut ion of t he opht halmic and, less of t en, t he maxillary divisions
of t he t rigeminal nerve. O ccasionally, oculosympat het ic paresis (w it hout
anhidrosis) may also occur. Because t he mandibular nerve is spared, no
mast icat ory paresis is evident .
The Superior Orbital Fissure Syndrome

The abducens, t rochlear, and oculomot or nerves as w ell as t he opht halmic
division of t he t rigeminal nerve pass t hrough t he superior orbit al f issure.
Theref ore, lesions at t he superior orbit al f issure (e. g. , t umor, t rauma, aneurysm,
inf ect ion) may cause complet e (ext ernal and int ernal) opht halmoplegia
associat ed w it h pain, parest hesias, and sensory loss in t he opht halmic
cut aneous dist ribut ion. O ccasionally, oculosympat het ic paresis (w it hout
anhidrosis) may occur because of t he involvement of t he sympat het ic f ibers.
Exopht halmos, due t o blockade of t he opht halmic veins, and blindness, due t o
ext ension of t he pat hologic process t o involve t he opt ic canal, may also occur.
Except f or t he occasional inst ance of involvement of t he maxillary division of t he
t rigeminal nerve in t he cavernous sinus syndrome, t he superior orbit al f issure
syndrome and t he cavernous sinus syndrome usually cannot be diff erent iat ed
clinically w it hout t he use of neuroradiologic procedures.
Lesions Affecting the Peripheral Branches of the

Trigeminal Nerve
The ophthal mi c di vi si on of t he t rigeminal nerve may be damaged in t he middle
cranial f ossa, at t he t emporal bone apex, at t he lat eral w all of t he cavernous
sinus, in t he superior orbit al f issure, or dist ally in t he f ace. Localizat ion of
opht halmic branch lesions in t he f ormer regions is made by associat ed cranial
nerve f indings, w hereas very dist al (e. g. , f acial) lesions result in sensory
dist urbances t hat are conf ined t o t he cut aneous supply of t he opht halmic division
or it s branches (e. g. , t he nasociliary, f ront al, and lacrimal nerves). Some degree
of corneal hypest hesia may occur in 45% of pat ient s w it h diabet es [7] and,
indeed, bilat eral corneal erosions and complet e corneal anest hesia may be t he
present ing f eat ure of diabet ic neuropat hy [22] .
The maxi l l ary di vi si on of t he t rigeminal nerve may be damaged at t he low er
lat eral w all of t he cavernous sinus, at t he f oramen rot undum, in t he
pt erygopalat ine f ossa, in t he f loor of t he orbit , at t he inf raorbit al f oramen, or in
t he f ace. Numbness or discomf ort in a maxillary dist ribut ion may be t he init ial
present at ion of a nasopharyngeal t umor [89] , as t hese t umors of t en arise in t he
lat eral nasopharyngeal w all (f ossa of Rosenmüller) and ext end t hrough t he
f oramen lacerum t o involve t he region of t he middle cranial f ossa and cavernous
sinus. Lesions aff ect ing t his nerve in t he cavernous sinus usually aff ect ot her
cranial nerves as w ell. More dist al lesions (e. g. , inf raorbit al nerve damage
secondary t o maxillary f ract ure) result in sensory dist urbances t hat are conf ined
t o t he cut aneous supply of t he maxillary nerve. Lesions in t he inf raorbit al
f oramen may cause t he numb cheek syndrome [ 11] , in w hich numbness involves
one cheek and t he upper lip in an inf raorbit al nerve dist ribut ion. The hypest hesia
in t his syndrome may also involve t he medial and lat eral upper incisors and
canine t eet h and adjacent gingiva but spare more post erior t eet h and gums (e. g. ,
t he molar and premolar t eet h and gums t hat are innervat ed by t he post erior and
middle superior alveolar nerves). I n t w o-t hirds of pat ient s, t he numb cheek
syndrome heralded recurrent squamous cell carcinoma of t he skin [11] . Because
of t he proximit y of dist al branches of t he f acial nerve t o t he inf raorbit al nerve,
lesions of t he f ace, especially squamous cell carcinoma, may cause paresis of
t he muscles of t he upper lip and angle of t he mout h w it h ipsilat eral low er lid
droop accompanied by cheek numbness (t he numb cheek–l i mp l ower l i d
syndrome) [8] . I nf raorbit al nerve-dist ribut ion pain may also be a complicat ion of
laser i n si tu kerat omileusis, probably because of manipulat ion of t he eyelid
speculum causing nerve injury [65] .
Musicians w ho play brass inst rument s (t rumpet , French horn, t rombone, t uba)
exert f orce on t he lip w it h t he mout hpiece of t he inst rument . This pressure may
injure t he ant erior superior alveolar nerve result ing in upper lip numbness and
pain (trumpet pl ayer's neuropathy) [33, 60] .
The mandi bul ar di vi si on of t he t rigeminal nerve may be damaged in t he f oramen
ovale, in t he zygomat ic f ossa, or in t he f ace. Lesions aff ect ing t hese regions
result in sensory dist urbances conf ined t o t he cut aneous supply of t he
mandibular division associat ed w it h ipsilat eral mast icat ory paralysis. A syndrome
of isolat ed ment al neuropat hy (the syndrome of the numb chi n or Roger's si gn)
[ 1, 4, 10, 26, 34, 46, 62 consist s of pain, sw elling, and numbness in t he jaw
(low er lip, chin, and mucous membrane on t he inside of t he lip). This syndrome is
usually seen in pat ient s w it h syst emic cancer (especially lymphoret icular
neoplasms and carcinoma of t he breast and lung) and may be due t o
compression of t he ment al or t he inf erior alveolar nerves by met ast ases t o t he
jaw [10, 62, 78] , int racranial involvement of t he mandibular nerve by base-of -
skull lesions [40, 41] , lept omeningeal seeding [81] , or neoplast ic perineural
inf ilt rat ion of t he ment al nerve [57] . A numb chin, due t o inf erior alveolar nerve
damage, may herald a relapse of mult iple myeloma [67] or be t he present ing
sign of Burkit t 's lymphoma in human immunodef iciency virus disease [6] . Proximal
versus dist al origin of t he syndrome depends on t he presence or absence of any
ot her cranial nerve (e. g. , cranial nerve VI or VI I ) involvement ; w it h
a proximal lesion, involvement of ot her cranial nerves or signs relat ed t o

lept omeningeal seeding may be expect ed rat her t han t he isolat ed f inding of
hypest het ic chin associat ed w it h a dist al lesion [62] . The pat t ern of oral
numbness may also help diff erent iat e bet w een dist al and proximal involvement of
t he t rigeminal syst em [10] . The incisive nerve, w hich cont inues in t he inf erior
alveolar canal beyond t he ment al f oramen, innervat es t he incisor, canine, and
bicuspid t eet h, and t heir numbness probably indicat es dist al involvement of t he
mandibular nerve; on t he ot her hand, lesions w it hin t he cent ral nervous syst em
may produce dissociat ion of sensory modalit ies and may spare dent al sensat ion
[ 39] . The est imat ed f requency of t he numb chin syndrome in breast cancer is
approximat ely 4% and is usually associat ed w it h a poor prognosis [46] .
Theref ore, pat ient s w ho develop a nont raumat ic ment al neuropat hy should
undergo a caref ul search f or malignancy, and chin numbness t hat occurs in a
pat ient know n t o have cancer may indicat e relapse and met ast asis. Anot her
st udy f ound t hat t he numb chin syndrome w as most of t en due t o dent al causes,
including f ollow ing dent al anest hesia or as a complicat ion of a dent al procedure,
pressure f rom ill-f it t ing dent ures in an edent ulous at rophic mandible in an elderly
pat ient , inf ect ion of t he root of a t oot h, acut e or chronic ost eomyelit is of t he
mandible, or odont ogenic or nonodont ogenic t umors or cyst s of t he mandible [4] .
The numb chin syndrome has also been described as t he f irst sign of giant cell
art erit is [37] .
I n a ret rospect ive evaluat ion of 42 pat ient s w it h cancer and numb chin syndrome,
breast cancer comprised 64% of t he primary t umors, and lymphoprolif erat ive
neoplasms comprised 14% [62] . Fif t y percent of t he pat ient s had mandibular
met ast ases, 14% had base-of -skull bone lesions, and 22% had lept omeningeal
seeding. The numb chin syndrome w as a lat e manif est at ion of malignancy,
associat ed w it h disease progression in 67% of t he pat ient s or heralding a
relapse, w hich w as of t en conf ined t o t he lept omeninges, in 31%. Median survival
af t er it s diagnosis w as 5 mont hs w hen due t o bone met ast ases and 12 mont hs if
associat ed w it h lept omeningeal seeding [62] . Bilat eral numb chin syndrome has
been described as t he init ial sympt om of Burkit t 's cell acut e lymphoblast ic
leukemia; post mort em examinat ion revealed direct inf ilt rat ion of t he mandibular
nerves by leukemic cells [57] . A burning sensat ion of t he low er lip f ollow ed lat er
by numbness may also occur w it h sickle cell disease, probably because of
inf arct ion of t he inf erior alveolar nerve or t he ment al nerve in it s canal [31] .
The peripheral branches of t he t rigeminal nerve are most of t en damaged in
isolat ion by t umors or by f ract ures of t he f acial bones or skull. Subacut e f acial
numbness may be t he heralding sympt om of an expanding t umor t hat involves t he
t rigeminal nerve f ibers [56] . Three pat ient s have been described w ho developed
subacut e f acial numbness as t he heralding sympt om of malignancy: an isolat ed
ment al neuropat hy as a result of met ast at ic bone dest ruct ion f rom a renal cell
carcinoma, a sensorimot or t rigeminal neuropat hy caused by direct compression
of t he semilunar ganglion by a cavernous hemangioma of Meckel's cave, and
f acial numbness as t he present ing manif est at ion of a primary brainst em
lymphoma. Cut aneous carcinomas of t he f ace (e. g. , squamous cell carcinoma,
basal cell carcinoma) and some nasopharyngeal carcinomas may present w it h
f acial dysest hesias in t he dist ribut ion of any branch of t he t rigeminal nerve [92] .
These report s demonst rat e t hat it is diff icult , init ially, t o diff erent iat e a “benign”
t rigeminal neuropat hy f rom serious condit ions associat ed w it h a poor prognosis.
Tongue numbness (unilat eral or bilat eral), of t en of sudden onset , may be seen in
t emporal art erit is [13] . I t is likely t hat ischemia of t he brainst em or lingual nerve
is responsible. Also, t ongue numbness may be part of t he neck-tongue
syndrome, in w hich sudden t urning of t he head result s in pain in t he upper neck
and occiput accompanied by numbness of t he ipsilat eral half of t he t ongue [58,
71] . This syndrome is t hought t o be because of irrit at ion of t he second cervical
dorsal root , w hich carries propriocept ive f ibers f rom t he t ongue t hrough t he
hypoglossal nerve, and it s communicat ions w it h t he second root . Lingual
pseudoat het osis may occur w it h t he neck-t ongue syndrome, presumably because
of lingual deaff erent at ion [71] .
Peri odi c hemi l i ngual numbness may occur in at t acks associat ed w it h
simult aneous submandibular sw elling and t ransient prof use salivat ion at t he
t erminat ion of t he event [83] . This periodic numbness is presumably due t o
int ermit t ent compression of t he lingual nerve due t o sialolit hiasis.
Numbness of half of t he t ongue may also occur w it h lingual nerve t rauma [69]
and w it h t rigeminal sensory neuropat hy relat ed t o collagen vascular diseases
[ 59] (see preceding t ext ). Lingual neuropat hy may result in hemilingual sensory
loss, pain, dysest hesia, parest hesia, and dysgeusia [38] . Lingual neuropat hy
may f ollow low er w isdom t eet h ext ract ion and ot her dent al procedures, surgery
of t he mandibular ramus, mandibular block anest hesia, endot racheal int ubat ion,
or t emporomandibular joint disc displacement [38, 61] .
The lingual nerve may also be ent rapped in t he lat eral pt erygoid muscle [61] .
Bilat eral ant erior lingual hypogeusia and hypest hesia has been described
f ollow ing a dent al procedure [85] . I n t his case, branches of t he lingual nerve
w ere damaged, as w ere t he chorda t ympani branches of t he f acial nerves, w hich
convey t ast e f rom t he ant erior t w o-t hirds of t he t ongue. Ageusia accompanied by
numbness of bot h sides of t he ant erior t ongue and perioral region (t he lat t er due
t o t rigeminal dysf unct ion conf ined t o t he lingual branches) may be t he init ial
manif est at ion of syndrome G uillain-Barré syndrome [17] .
Pat ient s may rarely develop neuromyot onia of t he f loor of t he mout h af t er
irradiat ion of t he mot or branch (V3) of t he t rigeminal nerve [27, 63] . The
neuromyot onia manif est s as episodic or sust ained muscle cont ract ion due t o
peripheral nerve dysf unct ion. The episodic involunt ary cont ract ion may also
aff ect t he low er f acial and mast icat ory (masset er) muscles [63] .
Jaw Drop
Pref erent ial w eakness of t he jaw -closure muscles (t emporalis and masset er
muscles) w it h preservat ion of jaw -opening muscles (pt erygoid muscles), w hen
severe, causes t he jaw t o hang open or be “dropped. ” Pat ient s have f at igue w it h
chew ing and t he need t o manually support t he jaw. This neurologic sign has been
most of t en described in myast henia gravis but may also occur in amyot rophic
lat eral sclerosis–Amyot rophic Lat eral Sclerosis (ALS) or myot onic dyst rophy
[ 91] . I n ALS, jaw drop is rarely an early f eat ure; rat her, t he t ongue muscles are
f requent ly t he earliest and most severely involved, suggest ing t hat t he
hypoglossal mot or nerve cells are part icularly suscept ible in ALS. Some pat ient s
w it h Kennedy's disease may present w it h jaw drop or isolat ed jaw -closure
w eakness [91] . Kennedy's di sease, or spi nal and bul bar muscul ar atrophy, is an
inherit ed X-linked degenerat ive disease of sensory and mot or neurons caused by
a t rinucleot ide (CAG ) repeat expansion in t he f irst exon of t he androgen recept or
(AR) gene. The dist inguishing clinical f eat ures of t he disease, include slow ly
progressive proximal great er t han dist al limb w eakness, bulbar w eakness
involving primarily f acial and t ongue muscles, perioral f asciculat ions, sensory
involvement , elevat ed creat ine kinase, and signs of androgen insensit ivit y
(gynecomast ia and t est icular at rophy) [91] .
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> Table of C ontents > C hapter 10 - C r anial Ner ve VII ( The Fac ial Ner ve)
Chapter 10
Cranial Nerve VII (The Facial Nerve)
Anatomy of Cranial Nerve VII (Facial Nerve)

Cranial nerve VI I (t he f acial nerve) (Fig. 10-1) is a mixed nerve w it h bot h mot or
and sensory component s. Fibers f rom t he motor di vi si on supply t he f acial
mimet ic musculat ure, t he st apedius, t he st ylohyoid, and t he post erior belly of t he
digast ric [4, 24] . I n addit ion, sensat ion of t ast e f rom t he ant erior t w o-t hirds of
t he t ongue and parasympat het ic f ibers is carried in a minor root called the
nervus i ntermedi us ( of Wri sberg).
Motor Division
Fibers of t his division arise f rom t he motor f aci al nucl eus, w hich lies in t he
ret icular f ormat ion of t he caudal pont ine t egment um, dorsal t o t he superior olive,
medial t o t he nucleus of t he spinal t ract of cranial nerve V (t rigeminal nerve),
and ant erolat eral t o t he nucleus of cranial nerve VI (abducens nerve). The f acial
nucleus is made up of f our separat e longit udinally orient ed cell groups
(subnuclei) t hat supply specif ic muscle groups [27] : (a) t he dorsomedial group t o
t he auricular and occipit al muscles, (b) t he int ermediat e group t o t he f ront alis
and corrugat or muscles, (c) t he vent romedial group t o t he plat ysma, and (d) t he
lat eral group t o t he buccinat or and buccolabial muscles. The orbicularis oculi
mot or neurons are localized t o a cap or clust er in t he dorsolat eral margin of t he
dorsal part of t he f acial nucleus. A diff erent somat ot opic organizat ion, how ever,
has been proposed, w it h f acial mot or neurons innervat ing t he low er f acial
muscles primarily f ound in t he lat eral part of t he nucleus, t hose supplying t he
upper f acial muscles f ound in t he dorsal part of t he nucleus, and t hose
innervat ing t he plat ysma and post erior auricular muscles f ound in t he medial part
of t he nucleus [74] . The i ntraponti ne roots arise dorsally f rom t he mot or nucleus
and run rost rally and dorsally (t he ascending int rapont ine root ) t o t he level of t he
nucleus of cranial nerve VI . The root t hen sw eeps over t he dorsal surf ace of t he
abducens nucleus (as t he genu of the f aci al nerve) and t hen passes
vent rolat erally and caudally t hrough t he pons t o emerge on t he lat eral aspect of
t he brainst em.
The supranuclear cont rol of f acial movement s occurs t hrough cort icobulbar f ibers
originat ing f rom t he low er t hird of t he precent ral gyrus. These f ibers course
t hrough t he corona radiat a, t he genu of t he int ernal capsule, and t he medial
port ion of t he cerebral peduncle t o reach t he pons. I n t he pons most f ibers
decussat e, ending in t he f acial mot or nucleus of t he cont ralat eral side. The
vent ral part of t he f acial nucleus, w hich innervat es t he low er t w o-t hirds of t he
f ace, has a predominant ly crossed supranuclear cont rol. Wit h supranuclear
lesions, t he dorsal port ion, w hich supplies t he upper t hird of t he f ace, has been
t hought t o be spared because it has bilat eral supranuclear cont rol. O t hers have
proposed t hat descending cort icof acial f ibers innervat e t he low er f acial mot or
nuclear region bilat erally, alt hough w it h cont ralat eral predominance, and t hat t he
upper f acial mot or nuclear region receives scant direct cort ical innervat ion f rom
eit her side of t he brain [74] .
This schema of supranuclear f acial muscle cont rol holds t rue f or volunt ary f acial
movement s. Emot ional involunt ary movement s and volunt ary f acial movement s
may be clinically dissociat ed, and t heref ore, a separat e supranuclear pat hw ay
probably exist s f or t he cont rol of involunt ary movement s. Spont aneous smiling,
but not t he volunt ary draw ing of t he corners of t he mout h t o say “cheese, ” is
rest rict ed in case of lesions of t he cont ralat eral
st riat um, globus pallidus, hypot halamus, and t halamus. Fibers mediat ing
emot ional f acial movement s do not descend in t he int ernal capsule in t heir
course t o t he f acial mot or nuclei. The right cerebral hemisphere is also involved
in cont rolling t he supranuclear emot ional f acial movement and is “dominant ” f or
t he expression of f acial emot ion [22] .
FI G URE 10-1 Schemat ic diagram of cranial nerve VI I (f acial nerve).
Nervus Intermedius (of Wrisberg)

The nervus int ermedius is t he sensory and parasympat het ic division of t he f acial
nerve. I t carries preganglionic parasympat het ic f ibers t o t he submaxillary
ganglion (post ganglionic f ibers go t o t he submandibular and sublingual glands)
and t he pt erygopalat ine or sphenopalat ine ganglion (post ganglionic f ibers go t o
t he lacrimal, palat al, and nasal glands). The nervus int ermedius also receives
sensory f ibers f rom t he geni cul ate gangl i on, w hich receives f ibers t hat carry t he
sensat ion of t ast e f rom t he ant erior t w o-t hirds of t he t ongue and also receives
aff erent s f rom t he mucosa of t he pharynx, nose, and palat e and f rom t he skin of
t he ext ernal audit ory meat us, lat eral pinna, and mast oid.
The parasympat het ic f ibers arise in t he superi or sal i vatory nucl eus of t he
pont ine t egment um; t hose cont rolling lacrimat ion arise f rom an associat ed
nuclear mass, t he l acri mal nucl eus. The gust at ory aff erent s end primarily in t he
nucl eus of the tractus sol i tari us of t he medulla, and t he ext erocept ive aff erent s
end in t he nucl eus of the spi nal tract of crani al nerve V in t he medulla. Some
propriocept ive aff erent s f rom t he f acial musculat ure also t ravel in t he f acial
nerve and have t heir perikarya in t he mesencephalic t rigeminal nucleus.
The sensory f ibers of t he nervus int ermedius t ravel t hrough t he subst ance of t he
pons lat eral t o t he mot or f ibers. Toget her w it h t he mot or divisions
of cranial nerve VI I medially, and cranial nerve VI I I (audit ory nerve) lat erally, t he
nervus int ermedius leaves t he pons in t he cerebellopont ine angle and ent ers t he
int ernal audit ory meat us.
Tears are produced by t he lacrimal glands (ref lex t ear secret ion), t he accessory
lacrimal glands of Krause and Wolf ring (basal t ear secret ion), and t he goblet
cells of t he conjunct iva [83] . Preganglionic parasympat het ic neurons responsible
f or lacrimal secret ion arise f rom t he l acri mal nucl eus of t he pons. Their axons
t ravel in t he nervus int ermedius, w hich passes t hrough t he cist ern of t he
cerebellopont ine angle t o join t he f acial nerve; t his nerve ent ers t he int ernal
audit ory meat us w it hin t he pet rous pyramid of t he t emporal bone. Wit hin t he
pet rous bone, t he axons dest ined f or t he lacrimal gland course t hrough t he
geniculat e ganglion w it hout synapsing and t hen separat e f rom t he f acial nerve t o
emerge f rom t he t emporal bone in t he f loor of t he middle f ossa as t he greater
superf i ci al petrosal nerve. The great er superf icial pet rosal nerve passes under
t he gasserian ganglion and ent ers t he vidian canal at t he ant erior end of t he
f oramen lacerum, w here it joins t he deep pet rosal nerve f rom t he carot id
sympat het ic plexus t o f orm t he vi di an nerve. This nerve passes t o t he
sphenopalat ine ganglion in t he pt erygopalat ine f ossa, w here t he preganglionic
lacrimal axons synapse w it h t he post ganglionic neurons. The post ganglionic
axons leave t he ganglion and ent er t he maxillary division of t he t rigeminal nerve
and t ravel int o t he inf erior orbit al f issure w it h it s zygomat ic branch. They run in
t he lat eral orbit and reach t he lacrimal gland t hrough t he anast omosis bet w een
t he zygomat icot emporal branch of t his division and t he lacrimal nerve, a branch
of t he opht halmic division of t he t rigeminal nerve [66] .
Anatomy of the Peripheral Course of the Facial Nerve

Af t er emerging f rom t he vent rolat eral pons, t he mot or division and t he nervus
int ermedius proceed lat erally in t he cerebellopont ine angle along w it h cranial
nerve VI I I . This nerve t hen ent ers t he i nternal audi tory meatus of t he t emporal
bone t oget her w it h t he audit ory nerve and t he int ernal audit ory art ery and vein.
Four port ions of t he f acial nerve can be dist inguished w it hin t he t emporal bone.
The M eatal (Canal) Segment

O n ent ering t he meat us, t he mot or division lies on t he superoant erior surf ace of
cranial nerve VI I I , w it h t he nervus int ermedius bet w een t his division and cranial
nerve VI I I . Wit hin t his segment , t he f acial nerve runs in close associat ion w it h
t he vest ibular and cochlear divisions of cranial nerve VI I I . There are no major
branches f rom t his segment of t he f acial nerve.
The Labyrinthine Segment
At t he lat eral end of t he int ernal audit ory meat us, t he mot or division and t he
nervus int ermedius ent er t he f aci al or f al l opi an canal in t he pet rous bone. The
labyrint hine segment runs almost at right angles t o t he pet rous pyramid and
courses ant erolat erally above t he labyrint h t o reach t he geni cul ate gangl i on,
w hich cont ains t he pseudounipolar perikarya of t he sensory f ibers of t he nervus
int ermedius. The f irst major branch of t he f acial nerve, t he greater superf i ci al
petrosal nerve, arises f rom t he apex of t he geniculat e ganglion. This nerve is
composed of preganglionic parasympat het ic eff erent s t hat innervat e t he lacrimal,
palat al, and nasal glands t hrough t he pt erygopalat ine (sphenopalat ine) ganglion.
The great er superf icial pet rosal nerve also cont ains cut aneous sensory aff erent
f ibers arising f rom t he skin of t he ext ernal audit ory meat us, lat eral pinna, and
mast oid.
The Horizontal (Tympanic) Segment

From t he geniculat e ganglion, t he f acial nerve runs horizont ally backw ard, below
and medial t o t he horizont al semicircular canal. No major branches of t he f acial
nerve originat e f rom t his segment .
The M astoid (Vertical) Segment

At t he post erior aspect of t he middle ear (sinus t ympani) t he f acial nerve again
changes course and bends inf eriorly as t he mast oid segment . The nerve to the
stapedi us muscl e originat es near t he upper end of t his segment . The ot her major
branch of t his segment is t he chorda tympani, w hich has a variable locat ion of
origin. The chorda t ympani joins t he lingual nerve and cont ains preganglionic
parasympat het ic f ibers (originat ing in t he superior salivat ory nucleus), w hich
innervat e t he submandibular and sublingual glands t hrough t he submaxillary
ganglion. The chorda t ympani also cont ains aff erent t ast e f ibers f rom t he
ant erior t w o-t hirds of t he t ongue dest ined f or t he nucleus of t he solit ary t ract .
Af t er giving off t he chorda t ympani, cranial nerve VI I exit s t he f acial canal
t hrough t he styl omastoi d f oramen. Near it s exit , it gives rise t o t he posteri or
auri cul ar nerve (t o t he occipit alis, post erior auricular, and t ransverse and
oblique auricular muscles), t he di gastri c branch (t o t he post erior belly of t he
digast ric muscle), and t he styl ohyoi d branch (t o t he st ylohyoid muscles). The
f acial nerve t hen pierces t he parot id gland w here it divides at t he pes anserinus
int o t he temporof aci al and cervi cof aci al branches, w hich f urt her divide int o
t emporof ront al, zygomat ic, buccal, marginal mandibular, and cervical branches.
These branches supply all t he f acial mimet ic muscles and t he plat ysma muscle.
Vascular Supply of the Facial Nerve

The int racranial port ion of t he f acial nerve is supplied by t he ant erior inf erior
cerebellar art ery–Ant erior I nf erior Cerebellar Art ery (AI CA) and t he int rapet rosal
port ion is supplied by t he superf icial branch of t he middle meningeal art ery and
t he st ylomast oid branch of t he post erior auricular art ery. The ext racranial part of
t he f acial nerve is supplied by t he st ylomast oid, post erior auricular, superf icial
t emporal, and t ransverse f acial art eries.
Clinical Evaluation of Cranial Nerve VII Function

Motor Function
The mot or f unct ions of t he innervat ed f acial muscles are assessed by f acial
inspect ion and t est s of f acial mobilit y. Symmet ry of blinking and lip movement s
w it h speech are not ed. The pat ient may be asked t o raise t he eyebrow s, w rinkle
t he brow, close t he eyes (orbicularis oculi), show t he t eet h w hile repeat ing a
sent ence w it h several labial consonant s (orbicularis oris), blow out t he cheeks
(buccinat or), and ret ract t he chin (plat ysma). Any asymmet ry of cont ract ion is
not ed. The st ylohyoid, post erior belly of t he digast ric, occipit alis, and auricular
muscles cannot be adequat ely t est ed. How ever, it must be kept in mind t hat t he
f acial nerve plays a role in t he oropharyngeal phase of deglut it ion t hrough t he
buccinat or, post erior belly of digast ric, perioral, and st ylohyoid muscles.
Weakness of t he st apedius muscle may be det ect ed by t he subject ive complaint
of hyperacusis, especially f or low t ones t hat sound louder on t he aff ect ed side
(because t he st apedius muscle no longer cont ract s adequat ely t o t ight en t he
ossicular chain and prot ect t he inner ear f rom loud noises).
Sensory Function
The sensory examinat ion of cranial nerve VI I essent ially consist s of evaluat ion of
t ast e on t he ant erior t w o-t hirds of t he t ongue. Each half of t he prot ruded t ongue
is t est ed w it h t he f our f undament al t ast es (sw eet , sour, salt y, and bit t er) and
asymmet ries document ed.
Reflex Function
The f acial nerve provides t he eff erent supply t o several ref lexes. The most
import ant of t he f acial ref lexes are t he corneal and palpebral ref lexes, w hich are
depressed on t he side of a low er mot or neuron–t ype f acial nerve lesion.
Consensual responses are spared. O rbicularis oculi (glabellar), orbicularis oris,
and palpebral ref lexes may also be depressed w it h inf ranuclear lesions.
Parasympathetic Function
I nf ranuclear f acial nerve lesions may result in increased or impaired lacrimat ion
t hat may be not ed subject ively by t he pat ient and can be t est ed by hanging
lit mus or f ilt er paper on each low er lid (Schirmer's t est ). Excessive salivat ion
may also be not ed w it h inf ranuclear lesions. O t herw ise, f acial parasympat het ic
f unct ion is diff icult t o t est object ively at t he bedside.
Localization of Lesions Affecting Cranial Nerve VII

Supranuclear Lesions (Central Facial Palsy)
I n supranuclear cort icobulbar lesions, t here is cont ralat eral paresis of t he low er
port ion of t he f ace w it h relat ive sparing of upper f acial f unct ion because t he
supranuclear cont rol of t he upper f ace has bot h ipsilat eral and cont ralat eral
component s, w hereas t he low er f ace has mainly cont ralat eral supranuclear
connect ions. The muscles around t he mout h are especially aff ect ed, but t here is
occasional paresis of t he low er or even t he upper orbicularis oculi. An alt ernat e
explanat ion f or t he predominance of low er f acial w eakness in upper mot or
neuron f acial palsies is t hat descending cort icof acial f ibers innervat e t he low er
f acial mot or nucleus bilat erally, alt hough w it h cont ralat eral predominance,
w hereas upper f acial mot or nuclear regions receive scant direct cort ical
innervat ion f rom eit her side of t he brain [74] . Theref ore, upper f acial movement s
are relat ively preserved in upper mot or neuron palsy because t heir mot or
neurons receive lit t le direct cort ical input , w hereas low er f acial muscles are
more severely aff ect ed because t heir mot or neurons normally depend on
signif icant cort ical innervat ion [74] .
O ccasionally, t here may be a dissociat ion bet w een volunt ary f acial movement s
(volit ional f acial palsy) and emot ional f acial movement s (emot ional or mimet ic
f acial palsy) [66] .
Volit ional f acial paresis w it hout emot ional paresis (e. g. , one side of t he
orbicularis oris may be
paret ic w hen t he pat ient speaks, or he or she may be unable t o ret ract t he angle
of t he mout h on command but does so w hen spont aneously laughing or crying) is
more common t han emot ional f acial paresis and may occur w it h cort icobulbar
int errupt ion f rom lesions of t he low er precent ral gyrus, int ernal capsule, cerebral
peduncle, or upper pons (above t he f acial nucleus) [66] . The reverse
dissociat ion, emot ional or mimet ic f acial paresis w it hout volit ional f acial paresis,
occurs w it h f ront al lobe lesions ant erior t o t he precent ral gyrus, especially if
t hey aff ect t he right cerebral hemisphere [22] . Unilat eral emot ional f acial paresis
has also been described w it h lesions of t he cont ralat eral supplement ary mot or
area, t he f ront al lobe w hit e mat t er, t he mesial t emporal lobe and insula, t he
st riat ocapsular t errit ory, t he ant erolat eral t halamus and insula, t he t halamus and
subt halamus, t he post erior t halamus, t he post erior t halamus and operculum, and
t he dorsal midbrain, as w ell as in post encephalit ic parkinsonism
[ 20, 54, 58, 66, 125] .
I solat ed volunt ary f acial paresis due t o a lacunar inf arct aff ect ing t he
cont ralat eral mediodorsal middle base of t he pons has been described [125a.
This case demonst rat es t hat f ibers conveying volunt ary orof acial act ivat ion
descend mediodorsally at t he level of t he middle pons and t hat f ibers conveying
emot ional act ivat ion may be assumed t o converge below t his level. The lesion
spares cort icolingual and cort icospinal connect ions but involves supranuclear
cort icof acial t ract f ibers.
Bilat eral upper mot or neuron lesions result in f acial diplegia associat ed w it h
ot her manif est at ions of pseudobulbar palsy (e. g. , spast ic t ongue, dysphagia,
uninhibit ed laught er, and crying).
Nuclear and Fascicular Lesions (Pontine Lesions)

Lesions w it hin t he pons may aff ect eit her t he nucleus of t he f acial nerve or it s
int rapont ine axons (f ascicles). These lesions usually aff ect neighboring
st ruct ures, such as t he abducens f ascicle or nucleus (lat eral rect us paralysis),
t he paramedian pont ine ret icular f ormat ion–Paramedian Pont ine Ret icular
Format ion (PPRF) (paralysis of conjugat e gaze t o t he ipsilat eral side), t he
cort icospinal t ract (cont ralat eral hemiplegia), and occasionally t he spinal t ract
and nucleus of t he t rigeminal nerve and t he spinot halamic t ract (ipsilat eral f acial
and cont ralat eral body sensory dist urbances). The associat ion of involvement of
t hese int raparenchymal st ruct ures w it h a f acial palsy indicat es a pont ine lesion.
Nuclear and f ascicular lesions of t he f acial nerve result in a peri pheral type of
f acial nerve palsy. Wit h complet e lesions, t here is unilat eral paralysis of all
mimet ic f acial muscles, w it h loss of f ront al w rinkling and f acial asymmet ry at
rest and w it h mot ion. The pat ient cannot f row n or raise t he eyebrow, close t he
eye, ret ract t he angle of t he mout h or purse t he lips, puff out t he cheek, or
t ight en t he chin on t he aff ect ed side. Wit h mild peripheral aff ect ion, only blink
asymmet ry (incomplet e blink on t he side of t he paresis) may be evident . O n
at t empt ing t o close t he eye on t he aff ect ed side, t he eyeball deviat es up and
slight ly out w ard (Bel l 's phenomenon) ow ing t o relaxat ion of t he inf erior rect us
and cont ract ion of t he superior rect us. Bell's phenomenon is a normal response
t hat becomes visible because of t he paralysis of eye closure; t his phenomenon
may not be present in 8% t o 10% of healt hy individuals, w ho inst ead show no
movement or dow nw ard eye movement s w it h f orced eye closure [50] . The cheek
puff s out during respirat ion, and f ood t ends t o accumulat e bet w een t he t eet h and
t he cheek on t he aff ect ed side ow ing t o buccinat or paralysis. This peripheral
t ype of f acial paralysis also result s in depressed corneal and palpebral ref lexes
on t he aff ect ed side w it h int act consensual responses and ipsilat eral
hyperacusis.
M illard-Gubler Syndrome
Millard-G ubler syndrome is caused by a lesion locat ed in t he vent ral pons t hat
dest roys t he f ascicles of t he f acial and abducens nerves and t he cort icospinal
t ract . I t is charact erized by t he f ollow ing signs:
1. I psilat eral peripheral-t ype f acial paralysis
2. I psilat eral lat eral rect us paralysis (diplopia w it h f ailure t o abduct t he
ipsilat eral eye)
3. Cont ralat eral hemiplegia
Foville Syndrome
Foville syndrome is caused by a lesion locat ed in t he pont ine t egment um t hat
dest roys t he f ascicle of t he f acial nerve, t he PPRF, and t he cort icospinal t ract . I t
is charact erized by t he f ollow ing signs:
1. I psilat eral peripheral-t ype f acial paralysis

2. Paralysis of conjugat e gaze t o t he side of t he lesion
3. Cont ralat eral hemiplegia
Eight-and-a-Half Syndrome
Eight -and-a-half syndrome is caused by a lesion in t he dorsal t egment um of t he
caudal pons involving t he PPRF or abducens nucleus and t he medial longit udinal
f asciculus–Medial Longit udinal Fasciculus (MLF), as w ell as t he
nucleus and f asciculus of t he f acial nerve [43] . I t is charact erized by t he

f ollow ing signs:
1. I nt ernuclear opht halmoplegia–I nt ernuclear O pht halmoplegia (I NO ) in addit ion

t o horizont al gaze palsy (one-and-a-half syndrome)
2. I psilat eral low er mot or neuron-t ype f acial palsy
Isolated Peripheral Facial and Abducens Nerve Palsy

I solat ed peripheral f acial and abducens nerve palsy is a syndrome caused by a
discret e lesion in t he caudal t egment al pons involving t he f acial nerve f ascicle (or
nucleus) and t he abducens nerve f ascicle [111] . I t is charact erized by t he
f ollow ing signs:
1. Peripheral-t ype f acial palsy

2. I psilat eral abduct ion w eakness
3. No ot her neurologic abnormalit ies
Posterior Fossa Lesions (Cerebellopontine Angle
Lesions)
I n t he post erior f ossa, t he mot or division of t he f acial nerve is in close proximit y
t o t he nervus int ermedius of Wrisberg and t he eight h cranial nerve. Lesions in
t his locat ion (e. g. , acoust ic neuroma, meningioma) result in:
1. I psilat eral peripheral-t ype f acial nerve paralysis (including loss of t ast e over
t he ipsilat eral ant erior t w o-t hirds of t he t ongue) w it hout hyperacusis (caused
by associat ed eight h cranial nerve aff ect ion)
2. I psilat eral t innit us, deaf ness, and vert igo
Cerebellopont ine angle lesions f requent ly ext end t o involve ot her neighboring
st ruct ures, including t he pons (nyst agmus or ipsilat eral gaze palsy), t he
cerebellar peduncles and cerebellum (ipsilat eral at axia), t he t rigeminal nerve
(ipsilat eral f acial pain and sensory changes), and t he abducens nerve (ipsilat eral
lat eral rect us paralysis). Aff ect ion of cranial nerves I X t hrough XI I may rarely
occur.
Lesions Affecting the Meatal (Canal) Segment of the

Facial Nerve in the Temporal Bone
I n t he t emporal bone, t he f acial nerve is closely associat ed w it h t he audit ory
nerve; t heref ore, lesions cause clinical f indings similar t o t hose seen w it h t he
cerebellopont ine angle syndrome: unilat eral f acial mot or paralysis, impairment of
t ast e over t he ipsilat eral ant erior t w o-t hirds of t he t ongue, impaired lacrimat ion,
and deaf ness (rat her t han hyperacusis). This syndrome is most of t en caused by
t emporal bone f ract ure and primary or secondary t umors.
Lesions Affecting the Facial Nerve Within the Facial

Canal Distal to the Meatal Segment but Proximal to the
Departure of the Nerve to the Stapedius Muscle
Lesions w it hin t he f acial canal dist al t o t he meat al segment but proximal t o t he
depart ure of t he nerve t o t he st apedius muscle involve t he mot or division of t he
f acial nerve and t he nervus int ermedius. There is no deaf ness or involvement of
ot her cranial nerves. The lesions result in ipsilat eral f acial mot or paralysis, loss
of t ast e over t he ant erior t w o-t hirds of t he t ongue, and hyperacusis. I f t he lesion
is proximal t o t he great er superf icial pet rosal nerve, lacrimat ion is impaired; if it
is dist al t o t his branch, lacrimat ion is normal. When t he geniculat e ganglion is
injured, pain may occur in t he region of t he eardrum. I nvolvement of t he
geniculat e ganglion by react ivat ion of lat ent varicella zost er virus–Varicella
Zost er Virus (VZV) result s in f acial paralysis, hyperacusis, and loss of t ast e
associat ed w it h geniculat e neuralgia and herpet ic vesicles on t he eardrum,
ext ernal audit ory meat us, or palat e (Ramsay Hunt syndrome). Hyperemia of t he
concha or helix occurs in some pat ient s. A variable degree of vest ibulocochlear
dysf unct ion occurs in approximat ely 20% of pat ient s. Somet imes, f acial paralysis
develops w it hout herpet ic erupt ion, a condit ion know n as zoster si ne herpete.
Lesions Affecting the Facial Nerve Within the Facial

Canal Between the Departure of the Nerve to the
Stapedius and the Departure of the Chorda Tympani
Lesions w it hin t he f acial canal bet w een t he depart ure of t he nerve t o t he
st apedius and t he depart ure of t he chorda t ympani cause f acial mot or paralysis
w it h loss of t ast e on t he ant erior t w o-t hirds of t he t ongue. Because t he lesion is
dist al t o t he nerve t o t he st apedius, hearing is spared (no hyperacusis).
Lesions Affecting the Facial Nerve in the Facial Canal

Distal to the Departure of the Chorda Tympani
Lesions in t he f acial canal dist al t o t he depart ure of t he chorda t ympani (e. g. ,
lesions at t he st ylomast oid f oramen) cause f acial mot or paralysis w it hout
associat ed hyperacusis or loss of t ast e.
Lesions Distal to the Stylomastoid Foramen

Lesions dist al t o t he st ylomast oid f oramen produce isolat ed f acial mot or
paralysis. I ndividual mot or branches of t he f acial nerve may be aff ect ed,
t hereby causing paralysis of individual f acial muscles. I n t his locat ion, t he f ibers
of t he f acial nerve may be involved by inf lammat ion of t he ret romandibular lymph
nodes or by t umors or inf ect ions (e. g. , sarcoidosis, inf ect ious mononucleosis) of
t he parot id gland. The f acial nerve or it s branches are also suscept ible t o f acial
t rauma (e. g. , by obst et ric f orceps) and ot her surgical misadvent ures [84a. O t her
causes of peripheral f acial nerve palsy are list ed in Table 10-1 and include Lyme
disease, leprosy, and acquired immunodef iciency syndrome–Acquired
I mmunodef iciency Syndrome (AI DS) [16, 32, 63, 132] . A peripheral f acial nerve
palsy has rarely been described in pat ient s w it h a lat eral medullary syndrome of
Wallenberg and at t ribut ed t o t he involvement of t he f acial nucleus or int ra-axial
f acial nerve f ascicles result ing f rom t he ext ension of t he lesion in t he low er pons.
A f amilial syndrome of hyperost osis cranialis int erna may cause recurrent f acial
nerve palsies (cranial nerves I , I I , and VI I I may also be aff ect ed) [15] . This
aut osomal dominant disorder causes cranial neuropat hies t hrough hyperost osis
and ost eosclerosis of t he calvaria and base of t he skull. O t her f orms of f acial
paralysis t hat can be inherit ed in an aut osomal dominant manner include
idiopat hic f amilial f acial nerve paralysis, Melkersson-Rosent hal syndrome,
Möbius syndromebius syndrome, and heredit ary neuropat hies w it h liabilit y t o
pressure palsies [33] .
I diopat hic f acial palsy (Bel l 's pal sy) is one of t he most common condit ions seen
in neurologic pract ice, account ing f or approximat ely 50% of t he cases of
peripheral f acial paralysis [18] . Women are f urt her at risk w hen pregnant [65] .
The last t rimest er of pregnancy is considered t o be a t ime f or increased risk f or
t he development of Bell's palsy. Women w ho develop Bell's palsy during
pregnancy or puerperium should be closely monit ored f or preeclampsia or
art erial hypert ension [120a. The incidence of Bell's palsy is also higher in
pat ient s w it h diabet es as compared t o t he general populat ion. No relat ionship
has been demonst rat ed bet w een at mospheric f luct uat ions and Bell's palsy [36a.
Usually, unilat eral, clinical, immunologic, serologic, and hist opat hologic f indings
implicat e t he react ivat ion of herpes simplex virus–Herpes Simplex Virus (HSV)
w it hin t he geniculat e ganglion as t he major cause of Bell's palsy [3] . O t her
viruses implicat ed in t he et iology of idiopat hic peripheral f acial paralysis include
VZV, cyt omegalovirus–Cyt omegalovirus (CMV), Epst ein-Barr virus–Epst ein-Barr
Virus (EBV), mumps, and human herpes virus 6. Vesicles behind t he ear, w it hin
t he ext ernal meat us, or palat e should raise a suspicion of Ramsay Hunt
syndrome. An increased risk f or Bell's palsy w as also report ed w it h t he
administ rat ion of an int ranasal inact ivat ed inf luenza vaccine in Sw it zerland; as a
result of t hese observat ions, t he int ranasal vaccine w as removed f rom t he
market [97a.
Weakness conf ined t o one or t w o f acial muscles on t he same side of t he f ace
may be due t o f acial t rauma, parot id gland neoplasm, or perineural spread of
skin cancer [95a.
I nf lammat ion and edema of t he f acial nerve are implicat ed as t he cause of Bell's
palsy. Hist opat hologic and clinical evidence suggest t hat t he sit e of t he lesion is
w it hin t he conf ines of t he f allopian canal, part icularly at it s medial end. Most
pat ient s become aw are of t heir f acial palsy af t er aw akening. Pat ient s of t en
complain of acut e onset of ret roauricular pain, dysgeusia, hyperacusis, and
decreased t earing [2, 3] . Ret roauricular pain usually occurs around t he t ime of
onset of f acial paralysis but may precede it s onset by at least 2 w eeks [30a.
The f acial paralysis is of t en maximal at onset or may progress f or over 24 t o 48
hours. Caref ul ot oneurologic examinat ion is usually normal except f or variable
loss of f unct ion of t he sevent h cranial nerve. Transit ory numbness of t he f ace in
one or more divisions of t he t rigeminal nerve is also of t en report ed in
approximat ely 25% of pat ient s [2, 3] .
A small percent age of pat ient s have associat ed dysf unct ion of ot her cranial
nerves. According t o Adour et al. [2, 3] , idiopat hic f acial paralysis is part of
cranial polyneurit is, of t en involving t he t rigeminal, glossopharyngeal,
cochleovest ibular, and cont ralat eral (clinically unaff ect ed) f acial nerves. Pat ient s
w it h f acial paralysis may also suff er f rom problems w it h eat ing and drinking, and
t ransient dist urbance or oropharyngeal sw allow ing has been demonst rat ed
elect rophysiologically in approximat ely t w o-t hirds of pat ient s [119a.
Pat ient s w it h unilat eral f acial paralysis are at risk of developing corneal
ulcerat ion because of lagopht halmos. Ensuring adequat e corneal prot ect ion is
t he immediat e opht halmic priorit y. Some pat ient s may complain of epiphora, or
conversely of a dry eye. Bell's palsy is a self -limit ing condit ion. Most pat ient s
have a f avorable prognosis. Pat ient s w it h react ivat ion of VZV inf ect ion or loss of
t he st apedial ref lex may have a poorer prognosis f or f ull recovery. Rarely,
recovery may be f ollow ed by t ransient or long-last ing mot or dysf unct ion such as
mot or synkinesis, myokymia, blepharospasm-like act ivit y, or hemif acial mass
cont ract ions associat ed w it h normal f acial movement s. I n some cases, aberrant
regenerat ion may cause involunt ary t earing of t he eye on t he involved side
(crocodile t ears, Bogorad's syndrome), or gust at ory sw eat ing (Frey's
syndrome) w hen parasympat het ic f ibers t o t he salivary glands reinnervat e t he

sw eat glands [125b. Recurrence occurs in approximat ely 7% of pat ient s w it h
Bell's palsy [70] .
TABLE 10-1 Etiologies of Peripheral Facial Nerve

Palsies
Metabolic
Diabetes mellitus
Hypothyroidism
Uremia
Porphyria
Granulomatous and connective tissue diseases
Polyarteritis nodosa
Behçet's disease
Rheumatoid arthritis
Sarcoidosis
Infection
Otitis media and mastoiditis
Malaria
Osteomyelitis and petrositis
Syphilis
Leprosy (Hansen's disease)
Lyme disease
Leptospirosis
Meningitis
Encephalitis
Herpes zoster
Varicella zoster
Infectious mononucleosis
Poliomyelitis
Tetanus
Rubella
Mumps parotitis
Parotid abscess (suppurative parotitis)
Bacillus anthracis (cutaneous anthrax)
Parvovirus B19 infection
Human herpes virus 6
Cat scratch disease (Bartonella henselae)
Mycoplasma pneumonia
Rickettsioses
Cervical necrotizing fasciitis
Acquired immunodeficiency syndrome (human
immunodeficiency virus seroconversion)
Neoplasm
Cholesteatoma
Carcinoma of the ear
Parotid gland (benign and malignant neoplasms)
Facial nerve tumor
Glomus jugulare tumor
Meningioma
Leukemia (Leptomeningeal malignancy)
Yolk sac tumor (endodermal sinus tumor)
Rhabdomyosarcoma of the middle ear
von Recklinghausen's neurofibromatosis (NF 1)
Trauma
Temporal bone fracture
Birth trauma
Extratemporal lacerations
Iatrogenic injury (surgery of the diseased or
congenitally malformed ear, temporomandibular joint
operations)
Drug reaction
Lidocaine
Diatrizoate
Isoniazid
Interferon-α
Ribavirin
Cyclosporine neurotoxicity
Inactivated intranasal influenza vaccine
Stevens-Johnson syndrome
Congenital
Maternal thalidomide use

Möbius syndrome
Poland's anomaly
Miscellaneous
Guillain-Barré syndrome
Tick bite
Diphtheritic neuropathy
Paget's disease
Osteopetrosis
Temporal bone dysplasias
Hypertension in children
Hypertensive hemorrhage in facial canal
Diphtheria–pertussis–tetanus vaccination
Idiopathic familial nerve palsy
Melkersson-Rosenthal syndrome
Hyperostosis cranialis interna
Postoperative delayed facial nerve following vestibular
schwannoma surgery
Temporal bone arachnoid cyst
Kawasaki syndrome
Dental block
Inflammatory pseudotumor of the facial nerve
Hemophilia A (associated hemotympanum)
Lateral medullary infarction
Barotrauma
High altitude
Idiopathic (Bell's palsy)
I n highly endemic areas, Lyme disease, an art hropod-borne spirochet e (Borrel i a

burgdorf eri ) inf ect ion know n t o cause eryt hema chronicum migrans, headaches,
papilledema, cranial neuropat hies, meningomyeloneurit is, lymphocyt ic meningit is,
heart block, and art hrit is, may be responsible f or one-f ourt h of cases of
peripheral f acial palsy. Bilat eral f acial involvement occurs in one-f ourt h t o one-
t hird of cases [17, 62] .
Recurrent orof acial sw elling predominant ly aff ect ing t he lips, f ace, and eyelids;
unilat eral or bilat eral f acial nerve palsy; cheilit is; and f issured t ongue (scrot al
t ongue or lingua plicat a) def ine Mel kersson-Rosenthal syndrome [ 42, 60] , w hich
may be associat ed w it h a variet y of disorders, including hyperhidrosis,
acroparest hesia, migraine, ret robulbar opt ic neurit is, paresis of t he medial
rect us muscle, Crohn's disease, and seronegat ive oligoart hrit is [42] . The
complet e syndrome is present in only 25% of pat ient s [60] . Lingua plicat a and
f acial paralysis is seen in approximat ely half of t he pat ient s. Rarely, f acial palsy,
and lingua plicat a, t w o of t he main f eat ures of t he classic t riad of Mel kersson-
Rosenthal syndrome, have been described in associat ion w it h Waardenburg
syndrome, a condit ion charact erized by sensorineural hearing loss; pigment ary
dist urbances of t he hair and iris; and ot her development al def ect s [41] . Facial
paralysis and concurrent f acial sw elling is also an uncommon but w ell-described
complicat ion of inf ant ile cort ical hyperost osis, an inf lammat ory condit ion of t he
skelet on and some of t he cont iguous f asciae and muscles [29] . Rarely, recurrent
idiopat hic f acial nerve palsy is associat ed w it h episodes of opht halmoplegia and
f amilial aggregat ion [80a. Bilat eral f acial paralysis (f acial diplegia) is uncommon,
occurring <1% as f requent ly as unilat eral paralysis [76] . Bilat eral involvement
may be due t o congenit al development al anomalies or associat ed w it h inf ect ious,
t raumat ic, post inf ect ious, granulomat ous, or neoplast ic processes (Table 10-2)
[ 55, 76, 122] . Development al f acial diplegia may be secondary t o Möbius
syndromebius syndrome of bif acial paresis w it h abnormalit ies of horizont al eye
movement s, usually as a result of bilat eral hypoplasia or aplasia of t he sixt h and
sevent h cranial nerve nuclei. Development al f acial diplegia may also be
associat ed w it h Poland's anomaly (unilat eral pect oralis muscle hypoplasia w it h
ipsilat eral breast and upper limb abnormalit ies) [28] . Bilat eral f acial paralysis
may also occur w it h collagen vascular diseases or ost eopet rosis and may rarely
be idiopat hic (bilat eral Bell's palsies). Weakness of t he inf erior f acial muscles
should be diff erent iat ed f rom emot ional f acial paresis, charact erized by
w eakness of t he low er f acial musculat ure evident during emot ionally provoked
movement s but not during volunt ary cont ract ions [28a. Bilat eral f acial paralysis
must be diff erent iat ed f rom ot her causes of f acial w eakness or loss of f acial
movement s, as seen in myot onic dyst rophy, myast henia gravis, or Parkinson's
disease.
Facial nerve paralysis in children present s a special challenge. Part ial unilat eral
low er lip palsy in t he neonat al period may be caused by t he involvement of t he
depressor labii inf erioris muscle, w hich is innervat ed by t he marginal mandibular
branch of t he f acial nerve. This part ial paralysis may be associat ed w it h serious
cardiac, skelet al, and genit ourinary abnormalit ies [25] . Birt h t rauma result ing
f rom sacral prominence pressure on t he f et al f ace during labor account s f or
most cases of f acial nerve paresis in t he new born period [28] . Not every f acial
palsy is a Bell's palsy. Misdiagnosis of t he et iology of unilat eral f acial w eakness
is common. Alt hough Bell's palsy is st ill by f ar t he most common cause
encount ered, secondary causes of f acial nerve paralysis must be considered in
t he diff erent ial diagnosis of pediat ric pat ient s [121a. Facial palsy can result f rom
congenit al development al anomalies, skull f ract ures, iat rogenic injuries during
surgery of t he diseased or congenit ally malf ormed ear, hemot ympanum
associat ed w it h hemophilia A, hypert ensive hemorrhage in t he f acial canal,
ost eopet rosis, and hypert ension. I nvolvement of t he f acial nerve is common in
t he G uillain-Barré syndrome syndrome or t he Fisher variant of t he G uillain-Barré
syndrome. Prompt diagnosis of recurrent cent ral nervous syst em leukemia and
lymphoma, cerebellopont ine angle t umors, yolk sac t umors, and embryonal
rhabdomyosarcoma of t he middle ear is needed. Caref ul examinat ion of t he
middle ear is recommended in children w it h f acial w eakness. Middle ear t umors
should be considered in t he diff erent ial diagnosis of unresolved ot it is media,
part icularly w hen associat ed w it h persist ent ipsilat eral f acial paralysis. Cranial
nerve palsies are common in t uberculous meningit is and in a variet y of inf ect ious
and parainf ect ious disorders including Lyme disease, chicken pox, herpes zost er
ot icus (Ramsay Hunt syndrome), coxsackievirus, EBV, human immunodef iciency
virus–Human I mmunodef iciency Virus (HI V), human herpes virus 6 inf ect ion
[ 103a, Mycopl asma pneumonia, Parvovirus B19 inf ect ion, cat scrat ch disease,
acut e disseminat ed encephalomyelit is, complicat ions of
acut e and chronic ot it is media or necrot izing ot it is ext erna, and bact erial or
mycobact erial mast oidit is. Facial paralysis has also been report ed in children in
associat ion w it h Kaw asaki disease and as a result of ischemic vasospasm
associat ed w it h dent al blocks [17, 26, 31, 38, 52, 87, 104, 109, 112, 121] .
TABLE 10-2 Etiologies of Bilateral Facial Nerve

Palsies
Granulomatous and connective tissue disease
Polyarteritis nodosa
Sarcoidosis (Heerfordt's syndrome)
Sjögren's syndrome
Infection
Meningitis (e.g., Cryptococcus, tuberculosis)
Encephalitis
Otitis media
Mastoiditis
Leprosy (Hansen's disease)
Lyme disease
Leptospirosis
Malaria
Mycoplasma pneumonia
Epstein-Barr virus infection
Cytomegalovirus infection
Trichinosis
Poliomyelitis
Herpes zoster or simplex
Botulism
Tetanus
Diphtheria
Ehrlichiosis
Acquired immunodeficiency syndrome (human
immunodeficiency virus seroconversion)
Neoplasm
Pontine glioma
Extra-axial tumors (e.g., epidermoid cancer,
ependymoma, cholesteatoma)
Meningeal tumors (e.g., leukemia, lymphoma)
von Recklinghausen's neurofibromatosis
Trauma
Temporal bone fracture
Birth trauma
Extratemporal lacerations
Congenital
Maternal thalidomide use
Möbius syndrome
Poland's anomaly
Miscellaneous
GBS
Fisher variant of GBS (ophthalmoplegia, ataxia, and
areflexia)
Syndrome of acute ataxia, areflexia, and facial diplegia,
without ophthalmoplegia
Multiple idiopathic cranial neuropathies
Bulbospinal neuronopathy
Brainstem encephalitis
Amyloidosis
Stevens-Johnson syndrome
Diabetes mellitus
Multiple sclerosis
Idiopathic intracranial hypertension (pseudotumor
cerebri)
Porphyria
W ernicke-Korsakoff syndrome
Melkersson-Rosenthal syndrome
Osteopetrosis
Hyperostosis cranialis interna
Vascular lesions (e.g., pontine hemorrhage)
External carotid artery embolization
Ethylene glycol toxicity
Tangier's disease
Hereditary liability to pressure palsies
Bell's palsy (20% of cases)
GBS = Guillain-Barré syndrome.
Abnormalities of Tear Secretion

Supranuclear lesions causing pseudobulbar palsy are of t en associat ed w it h
inappropriat e spells of crying, of t en unaccompanied by sadness. Unilat eral
pont ine lesions aff ect ing t he f acial nucleus may aff ect t he superior salivat ory
nucleus (causing decreased salivary f low ) and t he lacrimal nucleus (causing an
associat ed dry eye). Lesions of t he brainst em may how ever produce f acial
paresis w it h sparing of bot h t ast e and t earing because t he mot or f ibers t o t he
f acial muscles are anat omically separat e f rom t he sensory-parasympat het ic
component s [96] . The nervus int ermedius is adjacent t o t he f acial nerve and
cranial nerve VI I I in t he cerebellopont ine angle and int ernal audit ory
meat us; lesions in t his area (e. g. , t umors) may t heref ore produce a dry eye
associat ed w it h ipsilat eral f acial paresis, loss of t ast e, hyperacusis, hearing
loss, and vest ibular sympt oms. A peripheral f acial palsy associat ed w it h
ipsilat eral reduct ion in ref lex t earing usually suggest s a lesion in t he pet rous
bone, t he cerebellopont ine angle, or bot h [90] . Acoust ic t umors in t he int ernal
audit ory canal may cause asympt omat ic def iciency of t earing on t he side of t he
lesion, of t en bef ore gross evidence of f acial paresis or corneal hypest hesia
[ 105] . O ccasionally, acoust ic t umors may cause excessive lacrimat ion (at t imes
only apparent during meals) on t he side aff ect ed by t he deaf ness [14, 105] .
Lesions of t he f loor of t he middle f ossa near t he gasserian ganglion (e. g. ,
t umors, pet rosit is, herpes zost er of t he gasserian ganglion, carot id art ery
aneurysms, t rauma, and surgery) may injure t he great er superf icial pet rosal
nerve, impairing t ear secret ion [90] . I mpaired t ear secret ion on t he side of an
acquired abducens nerve palsy indicat es a lesion, usually ext radural, in t he
middle cranial f ossa (especially nasopharyngeal carcinoma) [90] . Lesions of t he
sphenopalat ine ganglion (e. g. , t umors of t he pt erygopalat ine f ossa) produce
unilat eral decreased t earing and dryness of t he nasal mucosa, of t en associat ed
w it h parest hesia or hypest hesia in t he maxillary dist ribut ion of t he t rigeminal
nerve. Unilat eral reduced t ear secret ion in a pat ient w it h a know n t umor or
inf ect ion of t he maxillary or sphenoid sinus indicat es ext ension of t he disease
beyond t he conf ines of t he sinus [90] . Trauma or t umors, especially met ast at ic
carcinoma, may damage t he zygomat icot emporal nerve, result ing in reduced
ref lex t ear secret ion. Finally, reduced t ear secret ion may also occur w it h diff use
dysaut onomias, such as t he Riley-Day syndrome, acut e pandysaut onomia, or t he
Shy-Drager syndrome [90] .
Abnormalities of Eyelid Closure

Volit ional blinking is under precent ral supranuclear cort ical cont rol (bilat eral but
mainly cont ralat eral) and is mediat ed t hrough t he f acial nerves' cont rol of
orbicularis oculi f unct ioning. Emot ional and periodic (spont aneous) blinking are
probably cont rolled by ext rapyramidal pat hw ays originat ing f rom or conveyed
t hrough t he put amen and globus pallidus, cingulat e gyrus, amygdala, and
t halamus. The t ypical spont aneous, volunt ary, or ref lex blink consist s of a rapid
dow n phase f ollow ed by a slow er ret urn t o t he open posit ion, w it h dow n-phase
velocit ies nearly t w ice as f ast as up-phase velocit ies. The neural f iring pat t ern
underlying bot h t he upw ard and dow nw ard phases of t he blink are probably
similar t o t hat used in generat ing saccadic eye movement s (see Chapt er 8), w it h
t he dow n phase result ing f rom a pulse-t ype f iring pat t ern and t he up phase
(w hich requires a change in f inal lid posit ion) result ing f rom a pulse-st ep f iring
pat t ern. O pen eyelid posit ion is maint ained by t onic act ivit y of t he levat or;
inhibit ion of t he levat or and simult aneous cont ract ion of t he orbicularis oculi
result s in a blink.
I n a review of eyelid f unct ion, Schmidt ke and But t ner-Ennever [119] not ed t hat
t he role of t he upper eyelid as t he prot ect or of t he eye comprises a number of
separable f unct ions:
1. Tonic lid elevat ion w hen t he eyes are open

2. Volunt ary eye closure and eye opening
3. I nvolunt ary adjust ment of t he eyelid t o t he vert ical globe posit ion, t hat is,
lid–eye coordinat ion
4. Periodic and ref lex blinking
5. Firm eye closure in prot ect ive and expressive act s, f or example, sneezing
I n t he f irst t hrough t hird f unct ions, only t he levat or palpebrae muscle is act ive,
w hereas in t he last t w o f unct ions, diff erent part s of t he orbicularis oculi muscle
cont ract w hile t he levat or is synchronously inhibit ed. Theref ore, in f acial nerve
palsy, t he upper eyelid posit ion, gent le eye closure, and lid–eye coordinat ion are
unaff ect ed, w hereas blinking and f irm eye closure are w eak [79] .
The blink rat e is t hought t o ref lect cent ral dopaminergic act ivit y. Theref ore,
decreased f requency of periodic blinking may occur w it h progressive
supranuclear palsy and parkinsonism, but increased f requency of blinking may
occur w it h drug-induced dyskinesias, G illes de la Touret t e syndrome, and
schizophrenia [75] . I n pat ient s w it h parkinsonism, t he t iming and reciprocit y of
t he levat or and orbicularis oculi act ivit y may be dist urbed during blinking.
Coact ivat ion or t remor-like rhyt hmic reciprocal act ivit y of t he levat or and
orbicularis oculi may be present on light lid closure, w hereas lid–eye
coordinat ion remains int act [83] . This suggest s t hat , in addit ion t o t heir inf luence
on blink f requency, dopaminergic basal ganglia pat hw ays play a role in t he
inhibit ion of t he levat or during blinks and eye closure [119] . Loss of spont aneous
blinking has also been described in Balint 's syndrome (see Chapt er 20) and is
caused by bilat eral pariet ooccipit al lesions [130] .
Insufficiency of Eyelid Closure

I nsuff iciency of eyelid closure may be due t o supranuclear lesions or lesions of
t he brainst em
(cranial nerve VI I nucleus), peripheral f acial nerve, neuromuscular junct ion (e. g. ,
myast henia gravis), or muscles (e. g. , myot onic dyst rophy). Cort ical or
subcort ical lesions of t he precent ral gyrus may cause paresis of volit ional
cont ralat eral eye closure, relat ively sparing t he spont aneous and emot ional eye
closure. Acquired inabilit y t o w ink (Revilliod's sign) may be an early sign of
cort icobulbar disease. Nondominant f ront al lobe lesions, or, more commonly,
bilat eral f ront al lesions may result in compul si ve eye openi ng [ 19, 95] . These
pat ient s are unable t o init iat e bilat eral volunt ary eye closure despit e ret ent ion of
t he abilit y t o comprehend t he t ask and t he presence of int act ref lex eye closure.
Apraxia of lid closure has been described w it h Creut zf eldt -Jakob disease,
amyot rophic lat eral sclerosis, st at ic encephalopat hy, and progressive
supranuclear palsy [51, 56, 71, 81] . O ccasionally, only one lid is aff ect ed [19, 37] .
Callosal damage has been post ulat ed as a possible explanat ion f or t he observed
unilat eral impaired volit ional eyelid closure cont ralat eral t o an ant erior cerebral
art ery t errit ory inf arct ion [78a. Bilat eral hemispheric or unilat eral nondominant
hemispheric lesions may result in motor i mpersi stence—w hen t he pat ient is
request ed t o close t he eyelids and keep t hem closed, he or she is unable t o
complet e t he t ask [49] . The eyelids close, of t en develop a f ine t remor, and t hen
almost immediat ely reopen. Failure t o keep t he eyelid closed may occasionally
aff ect only t he cont ralat eral eyelid in case of unilat eral hemispheric lesions and
is more f requent af t er right -sided brain damage [37] . Mot or impersist ence may
occur w it h parkinsonism [83] . Because an inabilit y t o close t he eyes of t en t urns
int o closing impersist ence, bot h sympt oms are likely t o have a common basis
[ 119] . Because gent le eyelid closure occurs as a result of t he inhibit ion of t he
levat or palpebrae muscles, disorders of volunt ary lid closure are likely caused by
a def icit in t he cort ical inhibit ion of levat or f unct ion rat her t han of orbicularis
oculi act ivat ion [119] .
Excessive Eyelid Closure and Blepharospasm

Spasmodic cont ralat eral eyelid closure may occur w it h f ocal seizures (f ront al
epilept if orm f ocus). Excessive eyelid closure is how ever most of t en caused by
bl epharospasm, w hich consist s of repeat ed, involunt ary, bilat eral cont ract ures of
t he orbicularis oculi muscles t hat may render t he pat ient f unct ionally blind [59] .
Blepharospasm is most of t en idiopat hic (essenti al bl epharospasm) and is
considered a f ocal dyst onia [7, 72] . I t may occasionally be accompanied by
spasmodic dysphonia or axial dyst onia (e. g. , t ort icollis) [72] . Blepharospasm
may also occur w it h oromandibular dyst onia, as in Meige syndrome (idiopat hic
blepharospasm–oromandibular dyst onia), a condit ion probably relat ed t o
dopaminergic preponderance in t he st riat um [72] .
Blepharospasm has also been report ed in pat ient s w it h mult iple sclerosis lesions
of t he rost ral brainst em [73] and bilat eral inf arct ions of t he rost ral brainst em,
diencephalon, and st riat um [36, 77] . Asymmet ric blepharospasm may also occur
w it h lef t f ront al cort ical inf arct s [128a. Bilat eral t ransient blepharospasm can be
a f eat ure of nondominant st riat al inf arct ions [59a. Blepharospasm may also
occur w it h olivopont ocerebellar at rophy and may be caused by a rost ral
brainst em lesion disrupt ing cent ral dopaminergic and cholinergic pat hw ays,
result ing in t he disinhibit ion of brainst em ref lexes or denervat ion supersensit ivit y
of t he f acial nuclear complex [69] . I t may also occur as a consequence of
irrit able or painf ul ocular disease (e. g. , conjunct ivit is), w it h drug-induced t ardive
dyskinesia, as a post encephalit ic process, or w it h degenerat ive diseases such
as Parkinson's disease, Wilson's disease, Hunt ingt on's disease, progressive
supranuclear palsy, and Hallervorden-Spat z syndrome (pant ot henat e kinase–
associat ed neurodegenerat ion) [67] . Blepharospasm has also been described
w it h ret inal degenerat ion and f amilial apoceruloplasmin def iciency [93] and as a
f amilial syndrome w it h dyst onia and pigment ary ret inopat hy [34] . Rarely,
blepharospasm may occur on a f unct ional basis.
Ref l ex bl epharospasm may occur af t er severe hemiplegia in pat ient s w it h
lesions, usually vascular, aff ect ing predominant ly t he nondominant
t emporopariet al regions. This blepharospasm is usually limit ed t o t he
nonparalyzed side and is evoked w hen t he examiner t ries t o hold t he eyelids
open (t hought t o be caused by t he release of inhibit ion of a “primit ive” brainst em
ref lex). Af t er right middle cerebral art ery t errit ory inf arct ion, some pat ient s close
t he ipsilat eral right eye more t ight ly t han t he lef t eye [101] . Spont aneous eye
closure remains gent le and symmet ric.
Abnormal Facial M ovements and Their Localization

Abnormal f acial movement s may be classif ied (G upt a S. personal
communi cati on, 1982), as f ollow s:
1. Dyskinet ic movement s
2. Dyst onic movement s
3. Hemif acial spasm

4. Post paralyt ic spasm and synkinet ic movement s
5. Miscellaneous movement s
A. Facial myokymia (w it h or w it hout spast ic paret ic f acial cont ract ure)
B. Focal seizures
C. Tics and habit spasms
D. Fasciculat ions
E. Myoclonus
Dyskinetic Movements
O ral–f acial dyskinesia may express it self as a const ellat ion of involunt ary
movement s of t he f ace, jaw, lip, and t ongue [102] , including t he f ollow ing:
1. Facial grimaces, dist ort ions, expressions, and t w it ches

2. Wide opening, t ight closing, up and dow n movement s, and lat eral deviat ion of
t he jaw
3. Puckering, pursing, and opening and closing movement s of t he lips
4. Prot rusion, w rit hing, and dist ort ed post uring of t he t ongue
O ral–f acial dyskinesias may occur spont aneously (especially in t he elderly) but
are usually side eff ect s of neurolept ics, t he eff ect of lack of dent ures
(edent ulous dyskinesia), or associat ed w it h various ext rapyramidal diseases
(e. g. , Hunt ingt on's chorea, Wilson's disease, neuroacant hocyt osis) [21] .
O rof acial dyskinesias also occur in drug-naï ve pat ient s w it h schizophrenia,
suggest ing t hat abnormal involunt ary movement s, part icularly orof acial
dyskinesia, may represent a neuromot or component of schizophrenia [106] .
Dystonic Movements (Blepharospasm and

Blepharospasm with Oromandibular Dystonia)
Blepharospasm, a common f ocal dyst onia, is an involunt ary, spasmodic, f orcef ul
cont ract ion of t he orbicularis oculi t hat is alw ays bilat eral and symmet ric and
t hat may be episodic or sust ained. The spasm may spread t o involve ot her f acial
and cranial musculat ure. This condit ion usually indicat es t he presence of
ext rapyramidal disease (e. g. , Parkinson's disease, progressive supranuclear
palsy, t ardive syndromes due t o neurolept ics, lit hium int oxicat ion) and is
dist inguished f rom ot her f acial movement disorders by it s symmet ry [89] .
Blepharospasm has also been report ed in pat ient s w it h bilat eral t halamic inf arct s
[ 92] , put aminal hemorrhages [127] , and low er pont ine t egment al lesions [8] .
Pat ient s w it h blepharospasm of t en complain of an ocular f oreign body sensat ion
and phot ophobia. When severe, blepharospasm can int erf ere w it h t he abilit y t o
drive, w alk, or w ork. O ccasionally, t he use of sensory t ricks or geste
antagoni sti que may t ransient ly diminish t he sympt oms experienced by pat ient s
w it h blepharospasm [57] .
I diopat hic blepharospasm may be associat ed w it h oromandibular dyst onia, as in
Mei ge syndrome [ 72] . This syndrome consist s of a combinat ion of
blepharospasm plus oromandibular dyst onia, manif est ed by sust ained grimacing
around t he mout h, jaw clenching, plat ysma cont ract ion, and sust ained neck
f lexion. This disorder may spread beyond t he f acial and nuchal musculat ure t o
involve one or bot h arms and t he t runk. I t is of unknow n et iology, but basal
ganglia dysf unct ion, perhaps w it h a dopaminergic predominance, may be
involved. Brueghel syndrome is a rare dyst onia of t he mot or component of t he
t rigeminal nerve t hat t ypically involves involunt ary opening of t he mout h.
Addit ional f eat ures include upbeat ing nyst agmus and paroxysmal hyperpnea
[ 54a.
Hemifacial Spasm
Hemif acial spasm is a descript ive t erm f or a unilat eral, involunt ary, hyperact ive
dysf unct ion of t he sevent h cranial nerve [1, 11, 47, 53, 64, 94, 131] . Hemif acial
spasm is charact erized by t he insidious onset of painless, arrhyt hmic, t onic, or
clonic int ermit t ent spasms of t he orbicularis oculi during adult hood; t hese
spasms gradually progress dow nw ard t o involve all ot her muscles (especially t he
orbicularis oris muscle, buccinat or muscle, and/ or plat ysma) innervat ed by t he
f acial nerve on t he aff ect ed side [47] . Cases of at ypical hemif acial spasm,
charact erized by spasms st art ing in t he orbicularis oris and buccinat or muscles
and gradually spreading upw ard t o involve t he orbicularis oculi muscle, have
been unusual [116] . The st apedius muscle may be aff ect ed (int ermit t ent clicking
is heard ipsilat erally). The cont ract ions seen w it h hemif acial spasm are irregular,
int ermit t ent , usually unilat eral, and exacerbat ed by emot ional st ress, anxiet y,
nervousness, and f at igue [129] . They are occasionally associat ed w it h pain and
may persist during sleep, and ipsilat eral f acial w eakness may develop in chronic
cases, as w ell as in rare cases f ollow ing microvascular decompression [47, 84] .
When bilat eral, t hese spasms are asynchronous and asymmet ric on bot h sides of
t he f ace. Bilat eral alt ernat ing hemif acial spasm has been described, possibly
caused by mult iple sclerosis [126] .
Lesions causing hemif acial spasm report edly occur anyw here, f rom t he f acial
nucleus t o t he st ylomast oid f oramen [44] . Lesions locat ed in t he ipsilat eral
cerebellopont ine angle (e. g. , t umors, vascular malf ormat ions, dolichoect at ic
basilar art eries, aneurysms, and bony abnormalit ies of t he skull) t hat compress
or angulat e t he f acial nerve at or near t he root ent ry zone–Root Ent ry Zone
(REZ) are t he most common cause [1, 10, 40, 82] , but int rapont ine (e. g. , mult iple
sclerosis, int ramedullary t umors [100] , lacunar inf arct ion [5, 128) and
int rat emporal lesions (e. g. , hemangioma of t he geniculat e ganglion) have also
been described [9] . Unusual t ort uosit y of t he AI CA or post erior inf erior
cerebellar art ery–Post erior I nf erior Cerebellar Art ery (PI CA) is f requent ly f ound
during microvascular decompressive procedures [12, 115] . Hemif acial spasm has
even been described w it h ext ernal compression of t he dist al f acial nerve w it hin
t he parot id space [108] , w it h schw annomas arising f rom t he i ntermedi ate nerve
[ 80] , w it h a contral ateral vest ibular schw annoma t hat causes marked brainst em
displacement and dist ort ion [99] , and in associat ion w it h idiopat hic int racranial
hypert ension [120] . Cross t alk (proximal ephapt ic t ransmission) among f acial
nerve f ibers or a kindling eff ect due t o compression may mediat e t his disorder
[ 44, 48] . Part ial demyelinat ion and axonal degenerat ion of t he sevent h cranial
nerve due t o neurovascular compression have been report ed, and t hese changes
may be needed t o produce t his condit ion [114] . I n some cases, hemif acial spasm
may be associat ed w it h mult iple cranial neuropat hies; w hen coexist ent w it h
t rigeminal neuralgia, t he condit ion is know n as ti c convul si f [ 45, 86] . I n ot her
inst ances, hemif acial spasm may f ollow Bell's palsy or t raumat ic f acial injury
(post paralyt ic hemif acial spasm) [39] . Very rarely, hemif acial spasm is f ound in
young children and adolescent s; idiopat hic t hickening of t he arachnoid membrane
has been implicat ed as a pot ent ial put at ive mechanism in t hese cases [78] . Rare
f amilial cases suggest ing a genet ic predisposit ion have also been report ed
[ 129] .
Postparalytic Spasm and Synkinetic Movements

Af t er recovery f rom peripheral f acial nerve paralysis (e. g. , Bell's palsy), various
phenomena may occur. These include post paralyt ic hemif acial spasm, t he
“crocodile t ears” phenomenon (eat ing provokes lacrimat ion), f acial cont ract ures,
and various synkinesias (abnormal synchronizat ion of t he movement of diff erent
muscles t hat normally do not cont ract t oget her), such as cont ract ion around t he
mout h w it h eye blinking and eyelid closure on f ull opening of t he mout h or
movement of t he jaw lat erally (Marin-Amat syndrome or “inverse Marcus G unn
phenomenon”) [103] . Synkinesis most of t en occurs as a result of aberrant
regenerat ion of t he f acial nerve af t er injury, but it also rarely occurs in muscles
innervat ed by t w o diff erent cranial nerves, including a rare f acial–t rigeminal
synkinesis [113] . Wit h post paralyt ic muscle cont ract ure, t he more relaxed,
normal cont ralat eral side may appear w eak on casual inspect ion. How ever, w hen
f acial movement s are perf ormed, t he act ual st at e and side of t he pat hology are
revealed. These various abnormalit ies are probably secondary t o f ault y f iber
regenerat ion af t er peripheral f acial lesions or abnormal act ivit y of residual mot or
unit s.
Miscellaneous Movements
Facial M yokymia
Faci al myokymi a is a rare f acial dyskinesia charact erized by [61] f ine,
cont inuous, w ave-like, undulat ing movement s of t he f acial muscles (“bag of
w orms”), occasionally associat ed w it h f acial cont ract ure or w eakness. I n many
cases f acial myokymia is due t o int raparenchymal pont ine t egment al lesions
involving t he post nuclear, post genu port ion of t he f acial nerve (especially mult iple
sclerosis and t umor) [6, 68, 98, 124] , perhaps ow ing t o a “release phenomenon” in
t he f acial nerve nucleus (f acial nuclear disinhibit ion [88] ). G uillain-Barré
syndrome syndrome may also be associat ed w it h f acial myokymia [35, 85] . O t her
causes include syringobulbia [107] , cerebellar and cerebellopont ine angle
t umors, meningeal carcinomat osis or sarcomat osis, basilar invaginat ion,
phosgene poisoning, and cardiac arrest [30, 46, 96] . Facial myokymia may also
occur in cases of brain deat h [118] . Follow ing t imber rat t lesnake envenomat ion,
bilat eral f acial myokymia and myokymia of t he bit t en ext remit y invariably result s
[ 23] . I n a pat ient w it h syringobulbia and f acial myokymia, neit her t he f acial mot or
nucleus nor t he f acial nerve w as pat hologically involved [110] . The myokymia in
t his case w as hypot hesized t o be caused by t he int errupt ion of aberrant
cort icobulbar f ibers in t he medulla, w hich produced disinhibit ion of a “rhyt hmic
neural generat or” in t he f acial nucleus. Finally, f acial myokymia w as described
as a f alse localizing sign in a pat ient w it h obst ruct ive hydrocephalus and
resolved w it h shunt ing [117] . Benign myokymia in healt hy subject s is limit ed t o
t he eyelids; in most inst ances t he movement s occur due t o or are exacerbat ed
by f at igue.
Myokymia may be associat ed w it h spast ic paret ic f acial cont ract ure [91] . I n t his
disorder,
myokymia begins in t he orbicularis oculi muscle and gradually spreads t o involve
most of t he musculat ure on one side of t he f ace. At t he same t ime, associat ed
t onic cont ract ure of t he involved muscles develops, event ually result ing in
decreased volunt ary f acial movement s on t he involved side. The nasolabial
groove deepens, t he corner of t he mout h is draw n lat erally, t he palpebral f issure
narrow s, and all t he f acial muscles become w eak. Myokymia w it h spast ic paret ic
f acial cont ract ure is considered a sign of damage t o t he dorsal pons in t he
region of t he f acial nucleus and is especially seen w it h brainst em neoplasm
[ 79, 91, 123] . O culof acial or oculomast icat ory myorhyt hmia is considered t o be
almost pat hognomonic of Whipple's disease, a mult isyst em disorder caused by
Tropheryma whi ppl ei i [ 6a. Facial “myorhyt hmia” has also been associat ed w it h
t he use of int erf eron-α 2a [123a.
Focal Cortical Seizures

G ross, clonic movement s of t he f ace, usually spreading t o involve ot her muscles,
may be associat ed w it h an epilept ogenic f ocus aff ect ing t he f ront al lobe (low er
precent ral gyrus). Post ict al paralysis (supranuclear t ype) may occur t ransient ly.
Tics and Habit Spasms

Tics and habit spasms are abrupt , repet it ive, st ereot yped, simple or complex
movement s t hat of t en involve muscles out side t he dist ribut ion of t he f acial nerve
(e. g. , neck) and can be reproduced or inhibit ed volunt arily. They are t hought t o
be of psychogenic origin, but t heir associat ion w it h G illes de la Touret t e
syndrome (involunt ary t ic-like movement s or vocalizat ions, somet imes w it h
coprolalia) suggest s t he possibilit y of basal ganglia dysf unct ion.
Fasciculations
Fasciculat ions of t he f acial muscles (spont aneous t w it ches of individual muscle
f ascicles) may occur w it h any process t hat aff ect s t he f acial nucleus or nerve
(e. g. , amyot rophic lat eral sclerosis, int raparenchymal t umor). Fasciculat ions of
t he f acial muscles, t ongue, and limbs are also seen in t he Kennedy syndrome (X-
linked bulbospinal neuronopat hy), an X-linked recessive disorder result ing f rom a
t rinucleot ide repeat expansion in t he androgen recept or gene.
M yoclonus
Rhyt hmic f acial movement s may occur in associat ion w it h palat al myoclonus or
t remor, a rhyt hmic, cont inuous palat al cont ract ion t hat persist s in sleep and
occurs w it h lesions t hat aff ect t he red nucleus, inf erior olive, or dent at e nucleus,
or t heir connect ing pat hw ays (G uillain-Mollaret t riangle). St ernocleidomast oid
and f acial asynchronous myoclonus has also been report ed in associat ion w it h
dolichoect asia of t he vert ebral art ery displacing t he medulla oblongat a; a direct
compression of t he elevent h and sevent h cranial nerves by t he dolichoect at ic
vessel has been proposed as t he pot ent ial mechanism [97] . I solat ed unilat eral
right f acial ref lex myoclonus has also been report ed t o be t riggered by speaking
and w rit ing but not by nonlinguist ic t asks, suggest ing a lef t rolandic opercular
cort ical origin [13] .
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> Table of C ontents > C hapter 11 - C r anial Ner ve VIII ( The Ves tibuloc oc hlear Ner ve)
Chapter 11
Cranial Nerve VIII (The Vestibulocochlear Nerve)
Anatomy of Cranial Nerve VIII

The eight h cranial nerve consist s of t w o separat e f unct ional component s: t he
audi tory ( cochl ear) nerve concerned wi th heari ng and t he vesti bul ar nerve
concerned wi th equi l i bri um. The audit ory nerve receives inf ormat ion f rom t he
t onot opically organized cochlea, t he organ of hearing. The vest ibular nerve
derives it s input f rom t he saccul ar and utri cul ar macul es (w hich sense l i near
accelerat ion) and t he crist ae of t he semicircular canals (w hich sense angul ar
accelerat ion of t he head). Because of t his f unct ional dualism, t he t w o
vest ibulocochlear nerve component s are discussed separat ely.
The Auditory Pathways

The audit ory pat hw ays (Fig. 11-1) may be concept ualized as a f our-t iered
neuronal net w ork, as f ollow s: (a) audit ory (cochlear) nerve ext ending f rom t he
organ of Cort i t o t he cochlear nucleus, (b) f ibers f rom t he cochlear nucleus
crossing t o t he cont ralat eral inf erior colliculus, (c) f ibers f rom t he inf erior
colliculus ext ending t o t he medial geniculat e body, and (d) f ibers f rom t he medial
geniculat e body project ing t o t he audit ory cort ex in t he superior t emporal gyrus
[ 20, 53, 82] .
First-Order Neurons
The audit ory recept ors are t he neuroepit helial hai r cel l s of t he organ of Cort i.
The st ruct ure of t he cochlea is such t hat hair cells locat ed at t he cochlear apex
are st imulat ed by low -f requency t ones, w hereas t hose locat ed at t he base are
st imulat ed by high-f requency t ones. First -order neurons of t he audit ory pat hw ay
have t heir cell bodies in t he spi ral gangl i on of the cochl ear nerve, w hich lies in
Rosenthal 's canal at t he base of t he bony spiral lamina. Aff erent component s of
t hese cells make cont act w it h t he hair cells of t he cochlea, t he majorit y
converging on t he inner hair cells and a smaller number diverging t o make
cont act w it h t he out er hair cells. When t he hair cells are act ivat ed, impulse
t ransmission is t riggered in f ibers having t heir perikarya in t he spiral ganglion;
t hese f ibers t hen ent er t he brainst em, at t he level of t he vent ral cochlear nuclei,
as t he cochlear nerve.
Second-Order Neurons
O n ent ry int o t he low er brainst em at t he junct ion bet w een t he medulla and pons,
t he aff erent cochlear nerve f ibers divide, innervat ing t he dorsal cochl ear nucl eus
and t he anteroventral and posteroventral nucl ei of t he cochlear complex. This
innervat ion f ollow s a t onot opic pat t ern. The more dorsal aspect s of t hese nuclei
receive f ibers t hat have innervat ed “high-f requency” (basal) hair cells, w hereas
t he vent ral aspect s receive f ibers f rom “low -f requency” (apical) hair cells. The
dorsal and vent ral cochlear nuclei cont ain t he second-order neurons and give
rise t o several project ions t o t he cont ralat eral brainst em, w hich ascend as t he
l ateral l emni scus, a f iber t ract t hat project s t o t he cent ral nucleus of t he inf erior
colliculus. These project ions include t he dorsal acousti c stri ae (f rom t he dorsal
cochlear nucleus), t he i ntermedi ate acousti c stri ae (f rom t he dorsal part of t he
vent ral cochlear nucleus), and t he ventral acousti c stri ae (f rom t he vent ral
cochlear nucleus), w hich is part of t he t rapezoid body. Decussat ing f ibers of t he
t rapezoid body and in t he cont ralat eral superior olivary complex ascend in t he
cont ralat eral lat eral lemniscus. The lat eral lemniscal f ibers ascend, w it h some
f ibers t erminat ing in t he lat eral lemniscal nuclei along t he w ay, and
t erminat e in t he i nf eri or colliculus. (The vent ral acoust ic st riae also t erminat e in
t he ipsilat eral and cont ralat eral ret icular f ormat ion, t he superior olivary nuclei,
and t he nuclei of t he t rapezoid body. )
FI G URE 11-1 The audit ory pat hw ays. (Adapt ed f rom St ockard JJ, St ockard
JE, Sharbrough FW. Det ect ion and localizat ion of occult lesions w it h
brainst em audit ory responses. Mayo Cl i n Proc 1977; 52: 761–769. )
Third-Order Neurons
The i nf eri or col l i cul us, locat ed in t he midbrain t ect um caudal t o t he superior
colliculus, cont ains t he t hird-order neurons and serves as t he cent ral relay
nucleus in t he audit ory pat hw ay, receiving ascending and descending input .
Basically, all ascending audit ory pat hw ays end in t he inf erior colliculus. Fibers
f rom t he lat eral lemniscus end in t he prominent cent ral nucleus of t he inf erior
colliculus, w hich has a t onot opic organizat ion. The project ions f rom t he inf erior
colliculus t erminat e in t he medi al geni cul ate body, w it h t he low -f requency f ibers
ending in t he apical–lat eral areas and t he high-f requency f ibers ending in t he
medial port ions of t his nuclear mass.
Fourth-Order Neurons
The medial geniculat e body is t he t halamic audit ory relay nucleus, and chief ly
gives rise t o t he geniculot emporal f ibers or audit ory radiat ions. The audit ory
radiat ions course lat erally in a dense t ract t hat part ly penet rat es t he vent ral and
lat eral port ions of t he post erior half of t he put amen and part ly runs in t he w hit e
mat t er below it [100] . Most f ibers t erminat e in lamina I V of t he primary audit ory
cort ex (AI , Brodmann's area 41), locat ed in t he t ransverse t emporal gyri of
Heschl, but some end in t he associat ion audit ory cort ex (AI I , Brodmann's area
42). The primary audit ory cort ex t erminat ions conf orm t o a t onot opic pat t ern,
w it h high-f requency t ones t erminat ing medially and low -f requency t ones
t erminat ing lat erally. Brodmann's area 41 is reciprocally connect ed w it h t he
vent ral division and Brodmann's area 42 w it h t he dorsal division of t he medial
geniculat e body. Through a large f iber t ract of t he corpus callosum, each
audit ory cort ical area is likew ise connect ed w it h t he reciprocal areas in t he ot her
cerebral hemisphere.
There are many commissural connect ions along t he audit ory pat hw ay; how ever,
none exist s at t he level of t he medial geniculat e body. The bilat eralit y of
represent at ion has obvious signif icance w hen unilat eral brainst em lesions are
considered. The neurons of t he superior olivary complex receive input f rom bot h
ears. There are connect ions bet w een t he t w o cochlear nuclei, connect ions
bet w een t he t w o dorsal nuclei of t he lat eral lemniscus t hrough t he commi sure of
Probst, connect ions bet w een t he inf erior colliculus on each side t hrough t he
commi sure of the i nf eri or col l i cul us, and connect ions bet w een t he cent ral
nucleus of t he inf erior colliculus and t he cont ralat eral medial geniculat e body
t hrough t he brachi um of the i nf eri or col l i cul us [ 79] . Anot her import ant
considerat ion is t hat f rom t he inf erior colliculus upw ard, t here are t w o diff erent
project ion syst ems. The f irst (including t he cent ral nucleus of t he inf erior
colliculus, port ions of t he medial geniculat e, and t he primary audit ory cort ex) is
ref erred t o as a core system, w hich is a direct audit ory pat hw ay w it h a t onot opic
organizat ion. The ot her (including t he pericent ral region of t he inf erior colliculus,
t he nonlaminat ed port ions of t he medial geniculat e body, and t he secondary
audit ory cort ex) is ref erred t o as a bel t projecti on, w hich has less t onot opic
organizat ion and serves as a polymodal syst em t hat receives bot h audit ory and
nonaudit ory inf ormat ion.
There are also several descending audit ory pat hw ays t hat run parallel t o t he
ascending f ibers and are int egrat ed in t he f eedback cont rol of audit ory input .
They include cort icogeniculat e f ibers, cort icocollicular f ibers, geniculocollicular
f ibers, collicular eff erent s, and an eff erent cochlear bundle f rom t he superior
olivary complex t o t he hair cells of t he spiral organ of Cort i.
The blood supply t o t he cochlea and audit ory brainst em nuclei arises f rom t he
int ernal audit ory (labyrint hine) art ery, usually a branch of t he ant erior inf erior
cerebellar art ery. Wit hin t he int ernal audit ory canal, t he int ernal audit ory art ery
supplies t he ganglion cells, nerves, dura, and arachnoid membranes, and t hen
divides int o t he common cochlear art ery and t he ant erior vest ibular art ery. The
superior olivary complex and lat eral lemniscus are supplied by circumf erent ial
branches of t he basilar art ery, t he inf erior colliculus is vascularized by branches
of t he superior cerebellar and quadrigeminal art eries, w hereas t he medial
geniculat e bodies receive t heir blood supply f rom t he t halamogeniculat e art eries.
Branches of t he middle cerebral art ery supply t he primary audit ory and
associat ed cort ices.
The Vestibular System

The vest ibular syst em monit ors angular and linear accelerat ions of t he head.
O ne use of t his inf ormat ion is t o monit or t he mot ion and posit ion of t he head in
space and t o maint ain balance. These accelerat ions are t ransduced int o neuronal
signals w it hin a specialized st ruct ure, t he membranous l abyri nth. The labyrint h
consist s of t he otol i th organ (ut ricle and saccule) and t he t hree semicircular
canals [2, 21, 29] . Linear accelerat ion is monit ored by specialized recept ors, t he
macul es, of t he ut ricle and saccule, w hereas angular accelerat ion is
monit ored by t he cri stae in t he ampullae of t he semicircular canals. These

recept ors are composed of numerous hair cells t hat serve as t ransducers,
convert ing mechanical movement s of sensory hairs int o changes of recept or
pot ent ials in t he hair cells and in t heir aff erent neurons.
The semi ci rcul ar canal s are t hree in number and are orient ed at approximat ely
right angles t o each ot her t o det ect angular accelerat ing movement s of t he head.
These canals include t he lat eral or hori zontal canal (w it h an out w ard convexit y),
t he anteri or or superi or canal (w it h an upw ard convexit y), and t he posteri or or
i nf eri or canal (w it h a backw ard convexit y). When t he head is in t he erect
posit ion, t he horizont al canal is almost horizont al (t here is a slight inclinat ion
dow n and back, f orming a 30-degree angle w it h t he horizont al), and t he superior
and post erior canals are arranged in t w o vert ical planes t hat f orm a 45-degree
angle w it h t he f ront al and sagit t al planes. Theref ore, t he horizont al canals of
bot h labyrint hs are in t he same plane, w hereas t he superior canal on one side is
in t he same plane as t he post erior canal of t he opposit e side.
The ut ricle and saccule are arranged at right angles also, w it h t he ut ricle parallel
t o t he base of t he skull and t he saccule parallel t o t he sagit t al plane [44] .
Theref ore, horizont al head movement s st imulat e t he ut ricle linearly, w hereas
t ilt ing t he head act ivat es t he saccule.
When t he crist ae or macules are st imulat ed, pot ent ials are developed in t heir
af f erent nerve endings, t he cell bodies of w hich lie in t he vesti bul ar gangl i on of
Scarpa housed in t he int ernal acoust ic meat us. These impulses are t hen
t ransmit t ed t hrough t he nerve f ibers t hat make up t he vesti bul ar nerve.
The inf ormat ion f rom t he membranous labyrint h is t ransmit t ed in a diff erent
manner in t he t w o diff erent component s of t he vest ibular nerve. The superior
port ion of t he nerve carries input f rom t he ant erior and horizont al semicircular
canals and f rom t he ut ricle, w hereas t he inf erior port ion of t he nerve t ransmit s
inf ormat ion f rom t he post erior semicircular canal and t he saccule. The vest ibular
nerve ent ers t he brainst em at t he pont omedullary level, bif urcat es int o ascending
and descending f ascicles, and t erminat es in t he vesti bul ar nucl ei (t he superior
nucleus of Becht erew, t he lat eral nucleus of Deit ers, t he medial nucleus of
Schw albe, and t he inf erior or descending nucleus of Roller), w hich lie in t he
rost ral medulla and caudal pons. The vest ibular nuclei init iat e cont ralat eral
vest ibulo-ocular responses and ipsilat eral vest ibulospinal ref lexes t o maint ain a
st able vision during head movement s and a st able post ure during body
movement s [58, 89] . The semicircular canals relat e pref erent ially t o t he superior
and medial vest ibular nuclei, w hereas t he macular f ibers project mainly t o t he
medial and inf erior vest ibular nuclei. O t her aff erent s of t he vest ibular nerve ent er
t he cerebellum by w ay of t he inf erior cerebellar peduncle and t erminat e in t he
vest ibulocerebellum.
Most of t he vest ibular nuclei out put is concerned w it h f eedback int egrat ion w it h
t he cerebellum, spinal cord, and brainst em. The main vest ibular connect ions
include t he f ollow ing st ruct ures.
M edial Longitudinal Fasciculus

Through t he medial longit udinal f asciculus–Medial Longit udinal Fasciculus (MLF),
t he vest ibular nuclei exert an inf luence on conjugat e eye movement s and on head
and neck movement s. Alt hough all t he vest ibular nuclei make cont ribut ions t o t he
MLF, only t he superior nucleus project s t o t he ipsilat eral MLF; ot her nuclei send
f ibers t o t he cont ralat eral MLF.
M edial Vestibulospinal Tract

The medial vest ibulospinal t ract arises primarily f rom t he medial vest ibular
nucleus, and t o a lesser ext ent , f rom t he inf erior and lat eral vest ibular nuclei.
Through t his t ract t he medial vest ibular nucleus exert s an excit at ory and
inhibit ory eff ect on t he cervical and upper t horacic levels of t he cont ralat eral
spinal cord.
Lateral Vestibulospinal Tract

This pat hw ay originat es primarily f rom t he lat eral and inf erior vest ibular nuclei
and project s t o t he ipsilat eral spinal cord. The f ibers dest ined f or t he cervical
cord arise f rom t he rost rovent ral port ion of t he lat eral vest ibular nucleus,
w hereas t he lumbosacral f ibers originat e f rom t he dorsocaudal port ion. The
lat eral vest ibulospinal pat hw ay f acilit at es ext ensor t runk t one and t he act ion of
ant igravit y axial muscles, ref lect ing t he input t he vest ibular nucleus receives f rom
t he ut ricular “gravit y det ect or. ”
Cerebellum
The vest ibulocerebellum receives aff erent f ibers f rom t he vest ibular ganglion and
f rom t he vest ibular nuclei of t he same side. The vest ibular nuclei (primarily t he
inf erior and medial nuclei) project t o t he ipsilat eral f locculonodular lobe and
uvula and t o t he f ast igial nucleus. The cerebellum also has reciprocal
connect ions w it h t he vest ibular nuclei including cerebellar cort icovest ibular f ibers
f rom t he nodulus, uvula, f locculus, and ot her areas of t he cerebellar vermis, and
f ast igiovest ibular
f ibers project ing f rom t he f ast igial nucleus. All of t hese connect ions course
t hrough t he juxt a-rest if orm body.
Reticular Formation
Through it s cerebellar project ions, t he vest ibular nuclei inf luence t he ret icular
f ormat ion (especially t he lat eral ret icular nucleus and t he nucleus ret icularis
pont is caudalis). The vest ibular nuclei also project f ibers back t o t he hair cells of
t he membranous labyrint h. These f ibers probably serve a modulat ing f unct ion.
Neurons in t he superior lat eral and inf erior vest ibular nuclei project bilat erally t o
t he vent ral post erolat eral and post erior nuclear group of t he t halamus. The
cort ical represent at ion of vest ibular f unct ion is locat ed in t he post cent ral gyrus
near areas 2 and 5 of t he cerebral cort ex. O t her recept ive areas include t he
f ront al lobe (area 6) and t he superior t emporal gyrus.
The bl ood suppl y t o t he membranous labyrint h is f rom t he int ernal audit ory or
labyrint hine art ery [74] . The lat t er usually arises f rom t he ant erior inf erior
cerebellar art ery but occasionally branches direct ly f rom t he basilar art ery. Af t er
giving off a branch t o t he eight h nerve in t he cerebellopont ine angle, t he int ernal
audit ory art ery t ransverses t he int ernal audit ory meat us and, at t he labyrint h,
branches int o (a) t he anteri or vesti bul ar artery t o t he ant erior and lat eral
semicircular canals and t he ut ricular macula, (b) t he posteri or vesti bul ar artery
t o t he post erior semicircular canal, t he saccular macula, and part of t he cochlea,
and (c) t he cochl ear artery. Theref ore, t he ant erior and post erior vest ibular
art eries supply st ruct ures innervat ed by t he superior and inf erior branches of t he
vest ibular nerve, respect ively.
Clinical Evaluation of Cranial Nerve VIII Function

Early diagnosis of deaf ness is crit ical, as it may lead t o learning disabilit ies and
impaired language skills.
Sensorineural Deafness
Sensori neural deaf ness ref ers t o a def icit in perceiving eit her t ones or speech,
w hich is due t o a lesion cent ral t o t he oval w indow. I t may t heref ore involve t he
cochlea (sensory), t he cochlear nerve and nuclei (neural), or t he cent ral audit ory
pat hw ays. Sensorineural deaf ness may be bilat eral and progressive (e. g. ,
presbycusis, ot ot oxic drugs), unilat eral and progressive (e. g. , Ménière's
disease, acoust ic neuroma), or unilat eral and sudden (e. g. , impaired cochlear
blood f low, viral inf ect ion, perilymphat ic f ist ula, aut oimmune inner ear disease or,
rarely, acoust ic neuroma) [66, 82] .
I ndividuals suff ering f rom sensorineural hearing loss f requent ly have diff icult y
hearing high-pit ched sounds and vow els (e and i t o a great er ext ent t han a, o, or
u). Formal audiomet ric t est ing usually reveals a loss of speech discriminat ion
t hat is out of proport ion t o associat ed pure t one deaf ness [34] . Pat ient s w it h
sensorineural pat hology of t en complain of ti nni tus, w hich varies in bot h pit ch and
int ensit y.
The evaluat ion of hearing loss begins w it h a t horough examinat ion of t he ext ernal
audit ory canal and an inspect ion of t he t ympanic membranes t hrough ot oscopy.
Next it must be det ermined w het her t he hearing loss is sensorineural, conducti ve
(i. e. , lesion locat ed bet w een t he environment and t he organ of Cort i), or mixed.
Hearing loss may be due t o a broad number of inherit ed and congenit al
disorders, inf ect ious, inf lammat ory, vasculit ic, met abolic, t raumat ic, and
st ruct ural condit ions, as w ell as select ive cochlear neurot oxicit y. Drug-induced
cochlear t oxicit y is a w ell-know n complicat ion of aminoglycoside ant ibiot ics, loop
diuret ics, nonst eroidal ant i-inf lammat ory drugs, quinine, and salicylat es. At
higher doses, aspirin can cause t innit us, dizziness, and hearing loss. Hearing
loss has also been report ed in associat ion w it h t he use of high doses of
propoxyphene and hydrocodone/ acet aminophen (Vicodin) [49, 85] .
Hearing loss is also a common complicat ion of cranial radiat ion. Hearing loss and
t innit us have also been report ed w it h t he use of Vinka alkaloids. O t ot oxicit y w it h
high-f requency sensorineural hearing loss is seen w it h t he use of cis-plat inum;
previous or concomit ant canal radiat ion may lead t o enhanced cis-plat inum
ot ot oxicit y. Hearing loss has also been report ed w it h t he use of int erf eron alpha
[ 60, 69, 80, 94] .
Common causes of conduct ive deaf ness are obst ruct ions of t he ext ernal audit ory
meat us by w ax, ot osclerosis, and middle ear diseases.
I n bedside qualit at ive assessment of hearing loss, a t uning f ork (256 or
pref erably 512 Hz) is used t o dist inguish bet w een t hese t w o t ypes of hearing
loss. Lat er, more f ormal quant it at ive audiologic t est s are perf ormed. Three major
t uning f ork t est s are used f or t he evaluat ion of hearing loss: Weber's, Rinne's,
and Schw abach's t est s.
The Weber's Test

The purpose of t he Weber's t est is t o help diff erent iat e a conduct ive f rom a
sensorineural hearing loss in a unilat eral hearing loss. This t est is
conduct ed by placing a vibrat ing t uning f ork over t he midline of t he skull or

f orehead, over t he nasal bone, or over t he ant erior upper incisors. Normally, t he
vibrat ions are perceived equally in bot h ears (no lat eralizat ion) because bone
conduct ion is equal bilat erally. I n conduct ive hearing loss, t he vibrat ions are
louder in t he deaf ear (lat eralized t o t he diseased ear). I n sensorineural hearing
loss, t he sound is louder in t he normal ear (lat eralized t o t he normal ear).
The Rinne's Test

The Rinne's t est compares t he pat ient 's air and bone conduct ion. The st em of
t he vibrat ing t uning f ork is applied against t he mast oid process. When t he pat ient
no longer hears t he vibrat ion, t he f ork is placed next t o t he ear (approximat ely 1
cm f rom t he ext ernal audit ory meat us) w it h t he t ines parallel t o t he sagit t al plane
of t he skull, one t o t w o inches f rom t he ext ernal audit ory meat us. I n normal
individuals, because air conduct ion is bet t er t han bone conduct ion, t he vibrat ions
are perceived in t he ear af t er t hey are no longer perceived at t he mast oid. The
Rinne's t est is said t o be normal, or posit ive, w hen t he t uning f ork is heard
approximat ely t w ice as long by air conduct ion as by bone conduct ion. I n cases of
conduct ion deaf ness, bone conduct ion is bet t er t han air conduct ion, and
t heref ore t he t uning f ork cannot be heard w hen it is placed next t o t he ear. Wit h
sensorineural hearing loss, bot h air and bone conduct ion are diminished t o a
similar ext ent , and air conduct ion remains great er t han bone conduct ion.
The Schw abach's Test

As in t he Rinne's t est , t he t uning f ork is held against t he mast oid process unt il
t he pat ient is unable t o perceive any sound. The examiner t hen places t he t uning
f ork over his or her ow n mast oid bone and compares t he bone conduct ion t o t hat
of t he pat ient . I f t he examiner hears t he t uning f ork af t er t he pat ient no longer
hears it , a sensorineural hearing loss is suspect ed.
I n summary, in sensorineural hearing loss:
1. The Weber's t est lat eralizes t o t he normal ear.

2. The Rinne's t est is posit ive (air conduct ion is bet t er t han bone conduct ion).
3. The Schw abach's t est demonst rat es t hat t he pat ient 's bone conduct ion is
w orse t han t he examiner's.
I n conduct ive hearing loss:
1. The Weber's t est lat eralizes t o t he diseased ear.

2. The Rinne's t est is negat ive (bone conduct ion is bet t er t han air conduct ion).
3. The Schw abach's t est is normal or prolonged (t he pat ient may hear t he
t uning f ork longer t han t he examiner does).
Vertigo and Vestibular Function
The clinical evaluat ion of a pat ient aff ect ed w it h dizziness or vert igo should f ocus
on t he f ollow ing f our areas [19, 46, 102] .
Definition of Characteristics of Symptoms

Di zzi ness is a nonspecif ic t erm of t en meaning diff erent t hings t o people (e. g. ,
light headedness, head sw imming, f aint ness or presyncope, disequilibrium,
dist urbance of consciousness, and t rue vert igo). Verti go is an illusion of mot ion
t hat some int erpret as subject ive (pat ient f eels t hat he/ she is spinning), or
object ive (t he environment seems t o be spinning). The most common illusion is a
spinning or w hirling sensat ion. Veget at ive sympt oms, such as nausea, vomit ing,
pallor, and sw eat ing, are f requent ly present in pat ient s w it h vert igo. Vert igo
arises f rom an imbalance of t he vest ibular t one and is usually associat ed w it h
disease of t he labyrint h or it s cent ral connect ions. The hist ory and physical
examinat ion should help dist inguish peripheral f rom cent ral causes of vert igo.
Nausea and vomit ing are much more common and severe w hen vert igo result s
f rom aff ect ion of t he peripheral vest ibular apparat us.
Vert igo must be diff erent iat ed f rom t he f ollow ing:
1. Light headedness or presyncopal f ai ntness, w hich is caused by decreased

blood f low t o t he brain.
2. Di sequi l i bri um, w hich is charact erized by an imbalance or unst eadiness
w hile st anding or w alking caused by loss of vest ibulospinal, propriocept ive,
visual, or mot or int egrat ion.
3. Nonspecif ic, vague sympt oms of f loat ing, sw imming, giddiness, rocking,
f alling, and spinning inside t he head. This is of t en due t o psychogeni c or
psychi atri c di sorders causi ng di zzi ness and may be seen among pat ient s
w it h anxiet y disorder (panic at t acks, agoraphobia, obsessive-compulsive
disorder), somat of orm disorders (including conversion disorder), and
depression. Hypervent ilat ion may also cause dizziness.
Associated Auditory Symptoms

I f unilat eral hearing loss accompanies vert igo, primary ear disease should be
suspect ed. A f eeling of “f ullness” in t he aff ect ed ear may occur
w it h ext ernal, middle, or inner ear pat hology. Autophony, or t he percept ion of t he
reverberat ion of t he pat ient 's ow n voice in t he aff ect ed ear, occurs only w it h
ext ernal or middle ear disease.
Ti nni tus is a sensat ion of noise in t he ears in t he absence of any signif icant
st imulus (i. e. , any perceived noise not produced by ext ernal audit ory st imuli).
Tinnit us is usually described as hissing, humming, w hist ling, or ringing. Tinnit us
may occur in t he cont ext of “normal” hearing, but may be associat ed w it h
vest ibular schw annomas, presbycusis, Ménière syndrome, chronic noise t rauma,
acut e acoust ic t rauma, ot ot oxicit y, vest ibulot oxicit y, and sudden hearing loss
[ 28] . Tinnit us may be paroxysmal or cont inuous, pulsat ile or nonpulsat ile, and is
more f requent ly not ed w it h peripheral rat her t han w it h cent ral lesions. Pat ient s
w it h unilat eral t innit us, pulsat ile t innit us, f luct uat ing t innit us, or t innit us
associat ed w it h vert igo must be t horoughly assessed f or pot ent ially severe
underlying pat hologic processes [70] . Low roaring t innit us suggest s Ménière's
disease, w hereas high-pit ched t innit us suggest s presbycusis or an acoust ic
t umor. Pulsat ile t innit us is usually a subject ive appreciat ion of t he pat ient 's
normal heart beat , but may also occur w it h a variet y of neoplast ic and congenit al
or acquired art erial or venous disorders including glomus jugulare t umors,
hemangiomas, meningiomas, art erial t ort uosit y or aberrancy, vascular loops,
persist ent st apedial art ery, high-grade carot id art ery st enosis, cervicocephalic
art erial dissect ions, int racranial aneurysms, int racranial art eriovenous
malf ormat ions, int racranial or ext racranial dural art eriovenous f ist ulae, high
jugular bulb, jugular divert iculum, dehiscent jugular bulb, enlarged jugular vein,
and venous st enosis. This t ype of t innit us may be decreased by t he Valsalva
maneuver, head t urning t o t he ipsilat eral side, or light pressure over t he
ipsilat eral jugular vein. Pulsat ile t innit us may also occur w it h idiopat hic
int racranial hypert ension [57, 77, 88] . Tinnit us f rom idiopat hic int racranial
hypert ension is t hought t o be due t o t urbulence of blood f low f rom t he
hypert ensive int racranial circulat ion int o t he low -pressure jugular bulb [77] .
G aze-evoked t innit us may develop af t er removal of cerebellopont ine angle
t umors (e. g. , acoust ic neuroma) [108] . This t ype of t innit us may be associat ed
w it h saccades, pursuit , and vest ibulo-ocular eye movement s. I t is post ulat ed t o
be due t o an abnormal int eract ion bet w een t he vest ibular and cochlear nuclei,
possibly due t o neural sprout ing af t er t ransect ion of t he audit ory nerve [108] .
O t her causes of t innit us include t emporomandibular joint disease, Paget 's
disease of t he bone, t hyrot oxicosis, anemia, sickle cell disease, cervical venous
hums, high cardiac out put , loud cardiac murmurs, labyrint hit is, perilymphat ic
f ist ulas, hydrocephalus, congenit al neurosyphilis, palat al myoclonus (palat al
t remor), pat ulous eust achian t ube, middle ear myoclonus, and t ensor t ympani
muscle spasm [51, 77] . Unusual st ereot yped episodes of oscillopsia and bilat eral
“sparking” t innit us occurring in a cyclic (every 100 ± 10 seconds) f ashion have
been described (periodic saccadic oscillat ions and t innit us), during w hich cycles
of disconjugat e opsoclonus, square-w ave jerks, and saccadic dynamic overshoot
disrupt st able f ixat ion (see Chapt er 8) [103] . I t is post ulat ed t hat t he lesion
responsible episodically disrupt s saccade-relat ed neurons and cent ral audit ory
neurons in t he pons.
Associated Symptoms Suggesting Central Neurologic

Dysfunction
Sympt oms and signs suggest ing brainst em, cerebellar, or cranial nerve
dysf unct ion (e. g. , diplopia, dysart hria, perioral numbness, drop at t acks, at axia,
et c. ) localize t he lesion t o t he cent ral pat hw ays. Associat ed audit ory
hallucinat ions suggest t emporal lobe disease.
Etiologic Search
An accurat e hist ory should reveal any associat ed viral inf ect ion, head or neck
t rauma, barot rauma, t oxin or drug exposure, alcohol abuse, endocrine and
met abolic diseases, cardiovascular disease, or previous luet ic inf ect ion.
All pat ient s should have a complet e ot ologic and audiologic evaluat ion and a
det ailed neurologic evaluat ion. This examinat ion should st ress t he f ollow ing:
1. Blood pressure evaluat ion in bot h arms (including t est s f or ort host at ic
changes), is done w it h a search f or cervical bruit s and cardiac arrhyt hmias.
2. A det ailed cranial nerve examinat ion is carried out , including repet it ion of
w hispering w ords and numbers, t uning f ork evaluat ion of hearing, and
examinat ion of ocular movement s, w it h special invest igat ion f or nyst agmus.
3. Cerebellar t est ing, especially evaluat ion of gait and st at ion abnormalit ies, is
perf ormed.
4. Evaluat ion of vest ibular cont rol of balance and movement is done. Wit h t he
Romberg t est (st anding w it h eyes closed and f eet t oget her) t he pat ient t ends
t o f all t o t he side of vest ibular hypof unct ion. Taking a f ew st eps w it h t he
eyes closed, t he pat ient t ends t o veer t o t he side of vest ibular involvement .
This phenomenon can be highlight ed by asking t he pat ient t o t ake
t hree st eps f orw ard and t hree st eps backw ard several t imes w it h t he eyes
closed. The t endency t o veer t o one side result s in a progressive deviat ion t o
t he impaired side. I nst ead of w alking in a line f orw ard and backw ard, t he
t raject ory of t he pat ient 's st eps resembles a st ar (“st ar w alking”). This
abnormalit y may be present w hen all ot her clinical t est s of vest ibular f unct ion
are negat ive. To examine t he eff ect of vest ibular f unct ion on dist al
movement s, t he pat ient may be asked t o place t he point ed index f inger of
t he out st ret ched arm on t op of t he examiner's f inger. The pat ient moves his
or her arm in an ample arc f rom above her head t o meet t he examiner's
f inger placed in f ront . Consist ent past-poi nti ng is f ound w it h bot h hands t o
t he side of a hypo-f unct ional vest ibular apparat us.
5. Provocat ive t est s are designed t o induce sympt oms or posit ional nyst agmus:
post ural changes, head t urning, sudden t urn w hile w alking, hypervent ilat ion,
provocat ive posit ioning maneuver (Nylén-Bárány or Dix-Hallpike t est ),
Valsalva's maneuver, and caloric t est ing.
Localization of Lesions Causing Deafness and Vertigo
Localization of Lesions Causing Sensorineural
Deafness
Cerebral Lesions
The human audit ory cort ex locat ed in t he superior t emporal gyrus along t he
Sylvian f issure (Brodmann's areas 41, 42, and 22) is subdivided int o an
audit osensory region (Brodmann's area 41) and an audit opsychic region
(Brodmann's areas 42 and 22).
Lesions of t he audit ory cort ex do not cause complet e deaf ness, even w hen
bilat eral. A subt le hearing impairment may be seen w it h unilat eral lesions, but
t his is more of t en charact erized by diff icult ies in localizing sounds. Unilat eral
dominant post erior t emporal lesions or bilat eral t emporal lesions aff ect ing
Heschl's gyri may cause pure word deaf ness. Pure w ord deaf ness, also know n
as audi tory verbal agnosi a, is charact erized by t he inabilit y t o underst and t he
spoken language despit e normal audit ory acuit y. I n t his condit ion, reading,
w rit ing, naming, and comprehension of nonlanguage sounds are also preserved
[ 40, 67] . Pat ient s w it h bilat eral lesions of t he audit ory cort ical regions manif est
a spect rum of disorders, ranging f rom cort ical deaf ness t o generalized audit ory
agnosia, select ive audit ory agnosia, pure w ord deaf ness, amusia, and milder
dist urbances in t he t emporal analysis of sounds [78] . The severit y of t he clinical
pict ure depends on t he ext ent of involvement of t he primary t emporal processing
syst em.
A number of pat ient s have been report ed w ho had severe hearing loss af t er
bilat eral t emporal or t emporopariet al lesions [4, 43, 100 or bilat eral subcort ical
lesions [100] . I n most cases, how ever, t he severe hearing loss is event ually
resolved, w it h only minor residual audiomet ric def icit accompanied by varying
degrees of impairment in t heir abilit y t o int erpret nonverbal as w ell as verbal
sounds (w ord deaf ness or audit ory agnosia) [100] . Wit h dichot ic list ening t asks,
t here is poorer perf ormance on st imuli present ed t o t he ear cont ralat eral t o a
lesioned Heschl's gyrus. Lef t hemispheric lesions predominant ly impair speech
discriminat ion, w hereas right hemispheric lesions predominant ly impair complex-
pit ch discriminat ion. Lesions in t he prenat al period cause t he same t ype of
def icit s but t o a lesser degree t han damage occurring in adult hood [83] .
I rrit at ive lesions of t he t emporal cort ex may result in subject ive audit ory
hallucinat ions. Audit ory hallucinat ions may be simple (e. g. , t innit us) or complex
(e. g. , voices, music). These audit ory sensat ions are most of t en ref erred t o t he
cont ralat eral ear and occur more f requent ly w it h irrit at ive lesions of Brodmann's
areas 42 and 22 t han w it h lesions of Brodmann's area 41. Part ial complex
seizures of t emporal lobe origin may st art w it h audit ory or vert iginous auras,
suggest ing an audit ory cort ical origin f or t he epilept if orm phenomenon [52, 68] .
Brainstem Lesions
I n general, because of t he binaural represent at ion of t he ascending audit ory
t ract s above t he level of t he cochlear nuclei, brainst em lesions involving t he
audit ory pat hw ays do not cause hearing impairment . Bilat eral hearing loss may
occur w it h severe bilat eral brainst em lesions (e. g. , hemorrhage or inf arct ion) and
has been described w it h lesions of t he t rapezoid bodies, pons, midbrain
t egment um, medial geniculat e bodies, and cochlear nuclei. Sudden audit ory
illusion of paracusis (hyperacusis) and palinacusis (perseverat ion of sounds)
have been report ed w it h small hemorrhagic lesions of t he medial geniculat e body
[ 39] . Associat ed brainst em f indings dominat e t he clinical pict ure. Neurologic
localizat ion may be assist ed by brainst em audit ory evoked pot ent ials and
magnet ic resonance imaging. Sudden bilat eral hearing impairment , occasionally
associat ed w it h t innit us and vert igo, w as described in 7 of 503 pat ient s w it h
vert ebrobasilar occlusive disease; 4 of t hese pat ient s w ere in a locked-in st at e
[ 55] .
Pineal and midbrain t umors may also cause sudden and complet e bilat eral
deaf ness (cent ral st em deaf ness of Brunner [97] ) presumably because t he
audit ory pat hw ays in t his region are closely packed t oget her in t he “ist hmus
acoust icus” [96] . Brainst em lesions in t he low er midbrain or rost ral pont ine
t egment um may also cause audit ory hallucinat ions associat ed w it h hearing loss
and a clear sensorium, likely due t o int errupt ion of t he cent ral audit ory pat hw ays
producing “release-t ype” hallucinat ions [26] . Brainst em audit ory hallucinosis has
also been described w it h low er pont ine t egment um hemorrhages [62] .
Peripheral Nerve Lesions and the Cerebellopontine

Angle Syndrome
Peripheral cochlear nerve lesions account f or part ial or complet e deaf ness, of t en
associat ed w it h ipsilat eral t innit us. Deaf ness is most prominent f or high-
f requency t ones and may be secondary t o t rauma (e. g. , basal skull f ract ure),
inf ect ions (e. g. , syphilis, bact erial inf ect ions), drugs (e. g. , st rept omycin,
neomycin), aneurysms of t he ant erior inf erior cerebellar art ery, or t umors of t he
cerebellopont ine angle (e. g. , vest ibular schw annomas, epidermoids,
meningiomas, arachnoid cyst s). Nearby cranial nerves (e. g. , V, VI , VI I , I X, X,
and XI ) may be aff ect ed; t heir involvement assist s in localizing t he lesion.
The cerebel l oponti ne angl e syndrome is commonly caused by a vest ibular
schw annoma (acoust ic neuroma) [48] . O t her condit ions account ing f or t his
syndrome include meningiomas, congenit al cholest eat omas, arachnoid cyst s,
epidermoids, lipomas, vascular loops (ant erior inf erior cerebellar art ery,
post erior inf erior cerebellar art ery), vert ebrobasilar dolichoect asia, aneurysms,
art eriovenous malf ormat ions, and vascular t umors. Commonly, but improperly
called acousti c neuromas, t hese t umors originat e f rom t he vest ibular Schw ann
cells of t he eight h cranial nerve in t he int ernal audit ory canal at t he glial-
Schw ann cell junct ion. Vest ibular schw annomas account f or approximat ely 2% t o
8% of all int racranial t umors w it h an incidence of approximat ely 1: 100, 000. They
usually present w it h insidious and progressive sensorineural hearing loss w it h
early loss of speech discriminat ion and t innit us. I n a small percent age of cases
(6%-10%) deaf ness may occur suddenly, most likely due t o int rat umoral
hemorrhage or int ernal audit ory art ery occlusion. A sense of imbalance, unst eady
gait , or disequilibrium is a more f requent complaint t han vert igo, diseases t hat
may be present in 20% of pat ient s. O t her common sympt oms include t innit us,
headaches, and f acial parest hesias [38] . As t he t umor grow s, t he int ernal
audit ory meat us progressively w idens, and complet e ipsilat eral nerve deaf ness
ensues (t he t innit us subsiding as t he deaf ness progresses). Wit h medial t umor
grow t h, neighboring cranial nerves are aff ect ed, and event ually brainst em and
ipsilat eral cerebellar compromise occur w it h very large t umors. Progressive
t umoral enlargement may account f or hydrocephalus or sympt oms and signs of
increased int racranial pressure.
Dysf unct ion of neighboring cranial nerves varies according t o t he direct ion of
t umoral grow t h. Wit h ant erior ext ension, t he t rigeminal nerve (f acial numbness,
paroxysmal f acial pain, depressed ipsilat eral corneal ref lex) and abducens nerve
(w eakness of ocular abduct ion, horizont al diplopia) are compromised. Wit h
post eroinf erior t umoral ext ension, cranial nerves I X and X (dysphagia, absent
pharyngeal ref lexes, vocal cord paralysis) and cranial nerve XI (ipsilat eral
st ernocleidomast oid and t rapezius paresis) may be involved. I n eit her case, t he
f acial nerve is usually involved, result ing in f acial paresis, loss of t ast e on t he
ipsilat eral ant erior t w o-t hirds of t he t ongue, decrease in ipsilat eral t earing, and,
rarely, hypest hesia of t he post erior w all of t he ext ernal audit ory canal
(Hit selberg sign), w hich is innervat ed by a sensory branch of t he f acial nerve,
and hemif acial spasm [48, 50, 71, 73, 84] . I n pat ient s present ing w it h bilat eral
vest ibular schw annomas, neurof ibromat osis t ype 2 should be suspect ed [72,
109] .
Hearing loss (usually bilat eral and associat ed w it h t innit us) may occur in
associat ion w it h mult iple branch ret inal art ery occlusions and encephalopat hy
(Susac's syndrome) [99] . This t riad of microangiopat hy of t he brain and ret ina
w it h hearing loss occurs exclusively in young w omen. Bilat eral sensorineural
deaf ness and t innit us have also been report ed in cases of vert ebrobasilar
occlusive disease [64] . Sensorineural hearing loss may also occur in cases of
bact erial meningit is, syphilis, and several viral inf ect ions including herpes zost er
ot icus, measles, mumps, human immunodef iciency virus–Human
I mmunodef iciency Virus (HI V), aut oimmune labyrint hit is [45, 75] , and Ref sum's
disease, a rare aut osomal recessive condit ion result ing in t he accumulat ion of
phyt anic acid and charact erized clinically by a demyelinat ing neuropat hy, per
cavus, cerebellar at axia, anosmia, and sensorineural deaf ness [110] .
Localization of Lesions Causing Vertigo
Physiologic and clinical vert igo syndromes are commonly charact erized by a
combinat ion of phenomena involving percept ual, ocular mot or,
post ural, and veget at ive manif est at ions: vert igo, nyst agmus, at axia, and nausea
[ 18] . Vert igo is an illusion of movement result ing f rom misinf ormat ion of
cort icospat ial orient at ion. Nyst agmus arises f rom a direct ion-specif ic imbalance
in t he vest ibulo-ocular ref lex. At axia (or post ural imbalance) result s f rom
inappropriat e or abnormal act ivat ion of vest ibulospinal pat hw ays. Nausea and
vomit ing develop f rom chemical act ivat ion of t he medullary vomit ing cent ers [18] .
Localizing lesions causing vert igo may be approached by considering t hree
general cat egories: peri pheral causes (vest ibular labyrint hine disease), central
causes (dysf unct ion of t he vest ibular connect ions), and systemi c causes (e. g. ,
endocrine, hemopoiet ic, met abolic diseases) [32, 36, 44, 102] .
Peripheral Causes of Vertigo

Lesions of t he semicircular canals induce rot at ory sensat ions, w hereas disease
of t he ot olit h syst em (ut ricle and saccule) produces linear sensat ions of t ilt or
levit at ion. I n acut e vert igo due t o labyrint hine disease, t he diseased side may be
t he more act ive of t he t w o (irrit at ive phase) f or some hours or even days, but it
soon becomes less act ive (paret ic phase). When t he eyes are closed, pat ient s
f eel a rot at ional sensat ion t ow ard t he side opposit e t o t he paret ic labyrint h. By
cont rast , in t he paret ic phase t he eyes t end t o deviat e slow ly t ow ard t he side of
t he lesion, and t o t hat side, pat ient s t end t o past -point and f all w hen st anding
w it h eyes closed. Pat ient s w it h severe vert igo f eel most comf ort able lying on
one side, usually w it h t he aff ect ed ear uppermost , perhaps t o use ot olit h input s
in order t o decrease t he imbalance bet w een t he semicircular canals. I n pat ient s
w it h labyrint hine disease, acoust ic st imuli may induce paroxysms of vert igo,
oscillopsia, post ural imbalance, t he ocular t ilt react ion, and nyst agmus (Tul l i o's
phenomenon), perhaps t hrough ut ricular st imulat ion [31] .
Peripheral vest ibular syndromes are usually of short durat ion and charact erized
by severe, of t en paroxysmal vert igo accompanied by audit ory dysf unct ion
(t innit us and hearing loss). Nyst agmus is of t en present and is charact erist ically
unidirect ional (f ast phase “aw ay f rom” t he side of t he lesion), horizont al rot at ory
(never vert ical or exclusively rot at ory), and inhibit ed by visual f ixat ion. The
subject ive environment al t w irl, past -point ing, deviat ion of t he out st ret ched hands,
and f all associat ed w it h t he Romberg's maneuver are t ow ard t he slow phase of
t he nyst agmus (t ow ard t he side of t he lesion). The peripheral vest ibular
syndrome is t heref ore compl ete (has all of t he clinical element s of vest ibular
dysf unct ion, e. g. , vert igo, nyst agmus, deviat ion of t he out st ret ched hands,
Romberg's sign, and so on) and congruent (all t he “slow deviat ions” are t ow ard
t he same side, i. e. , ipsilat eral t o t he responsible lesion).
Unilat eral t ot al loss of horizont al semicircular canal f unct ion (i. e. , canal paresis)
may be det ect ed by having t he pat ient f ixat e on a st at ionary t arget w hile t he
examiner t urns t he head f rom side t o side [47] . I n normal individuals, no
saccades (quick eye movement s) are not ed, indicat ing t hat t he subject 's gaze
remained f ixed on t arget . I n pat ient s w it h t ot al unilat eral canal paresis, one large
or several small opposit ely direct ed, compensat ory, ref ixat ion saccades occur
w hen t he head is rot at ed t ow ard t he lesioned side [47] .
Acquired vest ibular aref lexia, especially w hen bilat eral, may also result in head
movement –dependent oscillopsia, w hich is an illusory movement of t he visual
w orld t hat occurs only during head movement [104] .
Benign Paroxysmal Positioning Vertigo

Posit ional vert igo of t he benign paroxysmal t ype [6] , also know n as beni gn
paroxysmal posi ti onal verti go, or more appropriat ely benign paroxysmal
posit ioning vert igo–Benign Paroxysmal Posit ioning Vert igo (BPPV), is a very
common mechanical disorder of t he inner ear in w hich brief at t acks of acut e and
severe vert igo w it h concomit ant nyst agmus and aut onomic sympt oms is
precipit at ed by cert ain head movement s (of t en w hile pat ient s t urn in bed).
Cochlear or ot her neurologic sympt oms are t ypically absent , and t he sympt oms
usually abat e af t er 3 t o 6 mont hs. Nearly all pat ient s have at least one
exacerbat ion af t er an init ial remission [6] . Pat ient s are ot herw ise asympt omat ic
bet w een bout s [17] . BPPV can aff ect one or more semicircular canals, alt hough
involvement of t he superior semicircular canal is ext remely rare. Commonly,
BPPV involves t he post erior semicircular canal. BPPV may f ollow head t rauma,
viral labyrint hit is, Ménière's disease, migraines, or inner ear surgery, but most
cases (50%-70%) are primary or idiopat hic and best explained by t he
canal i thi asi s or cupul ol i thi asi s t heory [95] . Most cases of post erior canal BPPV
are due t o canalit hiasis [3, 87] . St ray ot oconial (calcium carbonat e cryst als)
part icles det ached f rom t he ot oconial layer (by degenerat ion or t rauma)
gravit at e and set t le on t he cupula of t he post erior semicircular canal (PC-BPPV),
causing it t o become heavier t han t he surrounding endolymph and t hus sensit ive
t o changes in t he direct ion of gravit y [17, 95] . Af t er rapid head t ilt t ow ard t he
aff ect ed ear or af t er head ext ension, w hen t he post erior semicircular canal is
moved in t he specif ic plane of st imulat ion, an ampullof ugal def lect ion of t he
cupula occurs, w it h t he development of a rot at ional vert igo af t er a short lat ent
int erval
and most commonly concomit ant upbeat geot ropic (“t ow ard eart h”) nyst agmus
w it h t he f ast phase beat ing t ow ard t he undermost ear. The nyst agmus t ypically
adapt s and f at igues af t er repeat ed posit ional t est ing [17] .
O t her pat ient s (10%-30%) display t he lat eral or horizont al semicircular canal
BPPV variant (HC-BPPV) in w hich t here is a st rong linear horizont al nyst agmus
beat ing t ow ard t he low ermost ear induced by rapid t urning of t he head f rom side
t o side around t he longit udinal axis. The nyst agmus exhibit s short lat ency w it hout
f at igabilit y, and of t en reverses it s direct ion on t he pat hologic side. The vert igo
can be induced by t urning t he head t o eit her side in t he supine posit ion, and is
alw ays more prominent on t he pat hologic side. The horizont al variant of BPPV
t ends t o resolve more quickly t han t he post erior canal BPPV. Tw o variant s of
HC-BPPV have been described: canalit hiasis and cupulolit hiasis of t he HC [105] .
Most cases of HC-BPPV are due t o cupulolit hiasis [56] . Some pat ient s exhibit a
combinat ion of PC-BPPV and HC-BPPV [8, 76, 86, 98] .
O t her causes of posit ional vert igo include t rauma, inf ect ion, ischemia [42] ,
demyelinat ing disease, neurosarcoidosis [106] , Chiari malf ormat ions, post erior
f ossa t umors, cochlear implant at ion [65] and perilymphat ic f ist ulas. Perilymphat ic
f ist ulas may be congenit al or acquired. Perilymphat ic f ist ulas usually f ollow
barot rauma result ing in an abnormal communicat ion bet w een t he perilymphat ic
space and t he middle ear. Barot rauma can occur during driving, playing, or
f ollow ing violent bout s of coughing or sneezing. Pat ient s experience at t acks of
imbalance or vert igo w it h increase in pressure in t he ear.
The provocat ive posit ioning maneuver (Dix-Hallpike or Nylén-Bárány maneuvers)
(pat ient is briskly moved f rom t he seat ed posit ion t o a posit ion w here t he head is
hanging 45 degrees below t he horizont al and rot at ed 45 degrees t o one side)
(Fig. 11-2) allow s f or a diff erent iat ion bet w een a peripheral or a cent ral origin
f or posit ional vert igo.
I n normal individuals, t hese maneuvers do not induce nyst agmus. Wit h peri pheral
l esi ons, vert igo, nausea, vomit ing, and nyst agmus appear several seconds (1 t o
15 seconds) af t er t he head posit ion is changed (lat ency of response due t o t he
period of t ime f or t he ot oconial mass t o be displaced). The nyst agmus is usually
t orsional, w it h t he upper pole of t he eye beat ing t ow ard t he ground. Fat igue w it h
repeat ed posit ioning is seen. The nyst agmus f at igues and abat es w it hin 10
seconds of appearance (f at igabilit y due t o dispersion of part icles in t he
endolymph), and w hen t he pat ient is rapidly brought back t o a sit t ing posit ion,
t he nyst agmus beat s maximally in t he opposit e direct ion (rebound). Wit h
repet it ion of t he maneuver, t he nyst agmus becomes progressively less severe
(habit uat ion).
A cent ral lesion should be suspect ed and f urt her invest igat ions init iat ed w hen (a)
t he posit ioning t est ing maneuver is posit ive w it h t he head t urned t o eit her side,
(b) t he nyst agmus changes direct ion immediat ely af t er t he shif t in posit ion and
remains f or as long as t he head is dow n, (c) t he nyst agmus is unaccompanied by
nausea or vomit ing, and if present , vert igo is mild and
last s <60 seconds, and (d) t he nyst agmus does not display f eat ures of
adapt abilit y or f at igabilit y.
FI G URE 11-2 The Dix-Hallpike or Nylén-Bárány maneuver.
Matuti nal verti go (vert igo precipit at ed by t he act of get t ing t o one's f eet on
aw akening in t he morning or somet imes on t urning over preparat ory t o rising)
may be cent ral or peripheral and, t heref ore, of no localizing nat ure [13] .
Mat ut inal vert igo is most f requent ly seen w it h disorders in w hich posit ional
f eat ures are prominent , and it is of t en prevent ed by having pat ient s sleep in a
semi-upright posit ion and be caut ious about easing out of bed in t he morning
[ 13] .
Peripheral Vestibulopathy
This t erm ref ers t o condit ions charact erized by acut e or recurrent at t acks of
episodic vert igo caused by ext ramedullary disorders of t he vest ibular syst em
[ 32] . Precise know ledge of t he sit e or nat ure of t he lesion is unknow n. These
condit ions encompass such ent it ies as acut e vest ibular neuronit is, acut e
labyrint hit is, epidemic vert igo, and viral labyrint hit is.
Acute vesti bul ar neuroni ti s, also know n as acute vesti bul ar neuri ti s,
neurolabyrint hit is, or unilat eral vest ibulopat hy of unknow n cause, is charact erized
by sudden at t acks of severe and prolonged vert igo, nausea, vomit ing, and
abnormal vest ibular f unct ion on caloric t est ing in ot herw ise healt hy pat ient s. The
vert igo t ypically develops over a f ew hours. I t is unrelat ed t o posit ional changes
of t he head and may be recurrent . Some pat ient s exhibit residual dizziness and
imbalance last ing f or mont hs [5] . Cochlear sympt oms are absent . Vest ibular
neuronit is has been at t ribut ed t o viral upper respirat ory inf ect ions, but t he
evidence t o support t hat not ion is slim. Theref ore, some aut hors pref er t he t erm
“acut e unilat eral peripheral vest ibulopat hy” [15] . Vest ibular neuronit is aff ect s
only a part of t he vest ibular nerve t runk, usually t he superior division (horizont al
saccular canal paresis), w hich t ravels separat ely and has it s ow n ganglion,
w hereas t he inf erior part (t he post erior semicircular canal) is spared [17, 24] .
Pat ient s may also have a combined superior and inf erior vest ibular neuronit is.
Acute l abyri nthi ti s resembles vest ibular neuronit is except t hat t here is
associat ed t innit us and sensorineural hearing loss. This syndrome may f ollow
syst emic, acut e, or chronic middle ear inf ect ions (i. e. , viral or bact erial
labyrint hit is) or occur in associat ion w it h ot ot oxic drugs such as aminoglycosides
and diuret ics (i. e. , t oxic labyrint hit is). Viral labyrint hit is have been report ed in
associat ion w it h measles, mumps, and rubella.
Di sabl i ng posi ti onal verti go [ 59] is a rat her poorly def ined syndrome
charact erized by const ant and disabling posit ional vert igo associat ed w it h severe
nausea (occasionally w it h t innit us) t hought t o be due t o int racranial compression
of t he vest ibular nerve by aberrant blood vessels.
Episodic vert igo f ollow ed by gait imbalance and oscillopsia may be f amilial
(aut osomal dominant ) [7] . Pat ient s w it h t his f ami l i al vesti bul opathy have
prof ound bilat eral vest ibular loss despit e normal hearing, somet imes in
combinat ion w it h a spinocerebellar at axia [92] . Also, paroxysms of vert igo and
visual blurring associat ed w it h complex combined t orsional, horizont al, and
vert ical nyst agmus have been described in associat ion w it h an art eriovenous
malf ormat ion in close proximit y t o t he vest ibular nuclei [63] . These episodes
occurred regularly at 2-minut e int ervals, each at t ack last ing f or 15 seconds. This
repeti ti ve paroxysmal nystagmus and verti go w as t hought t o be due t o
pat hologic brief burst s of hyperact ivit y of t he vest ibular nuclei [63] .
Epi sodi c verti go secondary to an abnormal ocul ovesti bul ar response may also
develop in relat ionship t o a variet y of opt okinet ic st imuli, such as w alking dow n a
grocery st ore aisle or driving a car [54] . Neurologic examinat ion, including
opt okinet ic responses, is normal. Pat ient s are of t en helped by t he administ rat ion
of acet azolamide. A f amilial acet azolamide-responsive vest ibulocerebellar
syndrome has also been described in pat ient s w it h long-st anding hist ories of
episodic vert igo, nausea, and vomit ing f ollow ed by a slow ly progressive t runcal
at axia [10] . O cular mot or signs bet w een at t acks included rebound and dow nbeat
t ype of nyst agmus. The at t acks decreased or abat ed f ollow ing t he administ rat ion
of acet azolamide.
Ménière's Disease
Ménière's disease is a progressive disorder charact erized by episodic acut e and
severe at t acks of vert igo, f luct uat ing sensorineural hearing loss, and t innit us.
Typically, t he hearing loss in t he early st ages of Ménière's disease aff ect s only
low f requencies, f luct uat es, and increases during t he acut e at t ack. Hearing
ret urns t o normal af t er each at t ack in t he beginning of t he disease, but as t he
disease progresses, residual hearing loss af t er each at t ack accumulat es and t he
hearing loss spreads t o higher f requencies. A subject ive dist ort ion of sounds may
also occur. There is also of t en a sensat ion of uncomf ort able pressure or f ullness
in and around t he aff ect ed ear.
Ménière's disease is more of t en unilat eral, alt hough it may be bilat eral in
approximat ely 20%-45% of cases. When bilat eral, t he disease is usually
asynchronous.
The et iology of Ménière's disease is unknow n. Pat hologically, t here is an
increased volume of endolymphat ic f luid leading t o dist ent ion of t he semicircular
canals: endol ymphati c hydrops. O t her
condit ions w here similar manif est at ions may be present (Ménière's syndrome)
include congenit al syphilis, viral and bact erial labyrint hit is, Mondini's dysplasia,
f enest rat ion of t he ot ic capsule, Paget 's disease, hypot hyroidism,
hyperlipidemia, diabet es mellit us, labyrint hine ot osclerosis, dysprot einemia,
leukemic inf ilt rat es, labyrint hine concussion, acoust ic t rauma, t emporal bone
t rauma, Cogan's syndrome, and vest ibular schw annoma [90, 91] .
Pat ient s w it h Ménière's disease complain init ially of dist ressing, f luct uat ing, and
episodic vert igo of variable durat ion and int ensit y. Most pat ient s have associat ed
nausea and vomit ing. Nonpulsat ile, low -pit ched, cont inuous t innit us, usually
described as “roaring, ” and sensorineural hearing loss may precede t he onset of
vert igo by mont hs or years. I ndividual at t acks last several minut es t o several
hours. Bet w een at t acks, pat ient s are init ially sympt om f ree but may complain of
some degree of disequilibrium. Event ually, t here is progressive det eriorat ion of
hearing, t ypically f or low -f requency t ones (below 3 kHz), w hich may culminat e in
complet e hearing loss. Tw o main variant s are recognized: cochl ear Ménière's, in
w hich vert igo and imbalance are absent , and vesti bul ar Mé nière's, in w hich
vert igo is prominent , but hearing loss, t innit us, and f ullness, or ear pressure are
absent in t he early st ages [1] .
A less common condit ion, know n as Tumarki n's otol i thi c catastrophe or ot holit ic
crisis is charact erized by acut e episodes of vert igo during w hich muscle t one and
pow er are lost . O n some occasions, pat ient s w it h Ménière's syndrome may also
develop drop attacks, described as a sensat ion of being pushed, t hrow n, or
knocked t o t he ground, or a sudden illusion of environment al movement t hat
causes t hem t o f all w it hout loss of consciousness [9] . The at t acks probably
result f rom a sudden mechanical def ormat ion of t he ot olit hic membrane of t he
ut ricle or saccule due t o pressure gradient s w it hin t he inner ear [9).
Vertigo Secondary to Middle Ear Disease

Vert igo of t he peripheral t ype may occur w it h acut e or chronic ear inf ect ion,
cholest eat oma, and congenit al or acquired syphilis. Congenit al syphilis should be
suspect ed in pat ient s present ing w it h sympt oms of bilat eral Ménière's syndrome.
Vertigo Secondary to Viral Infections

Varicella zost er inf ect ion of t he geniculat e ganglion may cause a vesicular
erupt ion of t he ext ernal audit ory meat us, or occasionally in t he t hroat , ear pain,
and a peripheral f acial paralysis. Spreading inf ect ion t o t he vest ibulocochlear
nerve may result in t innit us, vert igo, and hearing loss (Ramsay Hunt syndrome)
[ 12] .
Vertigo Secondary to Trauma

Closed head injuries or cervical t rauma may result in vert igo due t o inner ear
concussion, f ract ure of t he t emporal bone (damaging t he eight h nerve or
labyrint h), or “w hiplash” injury.
Central Causes of Vertigo

I n cont rast t o t he peripheral vest ibular syndrome, t he cent ral vest ibular
syndrome is of t en prolonged (permanent or chronic) rat her t han of short
durat ion.
Dysf unct ion of neighboring st ruct ures, including brainst em and cerebellar
st ruct ures, are usually present , w hereas audit ory sympt oms are less f requent .
Vert igo is less severe t han in t he peripheral syndromes and t ends t o be ill-
def ined and cont inuous in nat ure. The associat ed nyst agmus is bidirect ional or
unidirect ional, may be exclusively horizont al, rot at ory, or vert ical, and is not
alt ered by visual f ixat ion. The direct ions of subject ive environment al rot at ion,
past -point ing, deviat ion of t he out st ret ched hands, and Rombergism are variable
and barely alt ered by changes in head posit ion. The cent ral vest ibular syndrome
is t heref ore i ncompl ete or parti al (does not alw ays consist of all element s of
vest ibular dysf unct ion), and i ncongruent (t he nyst agmus and t onic deviat ions are
variable in direct ion).
Brandt [17] classif ied cent ral vest ibular syndromes of t he brainst em t egment um
int o t he f ollow ing t hree cat egories:
1. Disorders of t he vest ibulo-ocular ref lex–Vest ibuloocular Ref lex (VO R) in t he

horizont al (yaw ) plane (e. g. , horizont al nyst agmus and pseudovest ibular
neurit is due t o part ial ant erior inf erior cerebellar art ery or post erior inf erior
cerebellar art ery inf arct ion or a mult iple sclerosis plaque)
2. Disorders of t he VO R in t he sagit t al (pit ch) plane (e. g. , dow nbeat nyst agmus
and vert igo or upbeat nyst agmus and vert igo)
3. Disorders of t he VO R in t he f ront al (roll) plane (e. g. , t he ocular t ilt react ion)
Vascular Causes of the Central Vestibular Syndrome

These include t he f ollow ing disorders [35, 37, 41, 42, 101] :
Transi ent i schemi c attacks. I n general, isolat ed vert igo w hen present f or
more t han 6 w eeks is rarely at t ribut able t o vert ebrobasilar ischemia [37] .
I solat ed vert igo, isolat ed diplopia, isolat ed dysart hria, or isolat ed dysphagia,
should not be considered t o represent vert ebrobasilar t ransient ischemic
at t acks–Transient I schemic At t acks (TI As) unless t hey occur in combinat ion
w it h one anot her,
or w it h episodes of bilat eral or shif t ing mot or or sensory dysf unct ion,
complet e, or part ial loss of vision in bot h homonymous f ields, or any
combinat ion of t hese sympt oms [42] . Tinnit us and deaf ness are dist inct ly
uncommon manif est at ions of vert ebrobasilar ischemia [55] . I solat ed vert igo
on a vascular basis is best explained by t ransient ischemia t o t he vest ibular
labyrint h [41, 42] .
Labyri nthi ne stroke. A labyrint hine st roke may occur secondary t o
t hrombosis, art ery t o art ery embolism, or vasospasm of t he int ernal audit ory
art ery or one of it s branches. Vert igo, t innit us, nausea, and vomit ing result
(mimicking ot her nonvascular labyrint hine disorders), and, if t he cochlear
branch is also involved, deaf ness may also occur [42, 61] . Labyrint hine
hemorrhage may develop in pat ient s w it h leukemia, coagulopat hies, or
t umors.
Wal l enberg syndrome (l ateral medul l ary i nf arcti on). These pat ient s of t en
experience vert igo and an illusionary t ilt ing of t he environment by 90 t o 180
degrees. This syndrome consist s of a const ellat ion of signs and sympt oms
including ipsilat eral limb at axia, ipsilat eral f acial hypalgesia and
t hermoanest hesia, ipsilat eral paresis of t he pharyngeal muscles, ipsilat eral
Horner syndrome, and cont ralat eral t runk and ext remit y hypalgesia and
t hermoanest hesia. Nyst agmus and a host of oculomot or sympt oms may be
caused by compromise of t he ipsilat eral vest ibular nuclei.
O t her vascular causes of vert igo include basilar migraine [14] , subclavian
st eal syndrome, and cerebellar inf arct ion or hemorrhage. Main sympt oms of
cerebellar inf arct ion include vert igo, dizziness, nausea, vomit ing, gait
unst eadiness, inabilit y t o st and w it hout support even w it h eyes opened, limb
clumsiness, headache, dysart hria, diplopia, and decreased level of alert ness.
Most prominent signs include limb and gait at axia, dysart hria, nyst agmus not
suppressed by visual f ixat ion, and alt ered ment al st at us. Migraine probably
is t he most common cause of recurrent vert igo in children. Recurrent
monosympt omat ic spont aneous vert igo, or head mot ion int olerance,
occasionally mimicking BPPV may be due t o vest ibular migraine [30, 107] .
Most pat ient s do not f ulf ill I nt ernat ional Headache Societ y–I nt ernat ional
Headache Societ y (I HS) crit eria f or basilar migraine.
Multiple Sclerosis
Acut e vert igo is a common complaint in t he init ial episode of mult iple sclerosis,
and may also occur during relapses. Nyst agmus is also seen and may be
increased by head movement s [22] . This et iology should be considered only af t er
caref ul document at ion of disseminat ed cent ral nervous syst em–Cent ral Nervous
Syst em (CNS) lesions and a hist ory of remissions and exacerbat ions of
neurologic signs and sympt oms.
Wernicke's Encephalopathy
Wernicke's encephalopat hy is a t hiamine def iciency syndrome clinically
charact erized by a global conf usional st at e, at axia, and ext raocular muscle
palsies w it h nyst agmus. Despit e t he f requent involvement of t he vest ibular nuclei,
vert igo is an uncommon complaint .
Cerebellopontine Angle Tumors

Vert igo is not a prominent sympt om w it h cerebellopont ine angle t umors but may
be superimposed on t he more common f indings of slow ly progressive hearing
loss, t innit us, imbalance, and ot her cranial nerve or cerebellar abnormalit ies.
Vestibular Epilepsy
Episodic vert igo may represent t he aura or t he sole manif est at ion of a seizure
disorder, especially part ial complex seizures of t emporal lobe origin. O t her
t emporal lobe phenomena (e. g. , st aring spells, aut omat isms, audit ory
hallucinat ions, episodes of déjà-vu or jamais-vu) should be sought t o conf irm t his
as an et iology f or t he vert iginous sympt oms. Tornado epi l epsy is of t en
associat ed w it h a sense of spinning t hat mimics a peripheral vest ibulopat hy.
Other Central Nervous System Disorders

Many CNS disorders cause dizziness and disequilibrium. I n t he pediat ric
populat ion, cerebellar abnormalit ies (i. e. , congenit al absence of t he cerebellum,
hypoplasia of t he cerebellar vermis, Dandy-Walker syndrome), post erior f ossa
t umors and Chiari malf ormat ions are among t he most common implicat ed
condit ions.
Fami l i al peri odi c ataxi a. I ndividuals w it h t hese aut osomal dominant

syndromes have episodic dizziness, disequilibrium, and gait inst abilit y [25] .
Beni gn paroxysmal verti go of chi l dhood. Children aff ect ed by t his
nonepilept ic condit ion, likely t o be a migrainous precursor or equivalent may
present w it h brief spells, somet imes in clust ers, during w hich t hey of t en
appear f right ened, pale, and sw eat y, w it hout impairment of consciousness.
Caloric t est ing is report ed t o be abnormal in most of t hese children [11, 33] .
Elevat ion of serum creat inine kinase—MB values has recent ly been used as a
marker f or t he diagnosis of benign paroxysmal vert igo of childhood [93] .
Systemic Causes of Dizziness and Vertigo
Syst emic condit ions aff ect ing peripheral or cent ral vest ibular st ruct ures capable
of producing dizziness or vert igo [111] , include t he f ollow ing:
Cardi ovascul ar di sorders. Cardiac arrhyt hmias, aort ic st enosis or ot her

valvular lesions, congest ive heart f ailure, cardiomyopat hies, and carot id
sinus hypersensit ivit y may be associat ed w it h dizziness and syncope.
Vascul i ti des. Vert igo is a common manif est at ion of Cogan's syndrome, an
aut oimmune disorder charact erized by episodic vert igo, t innit us, hearing
loss, and nonsyphilit ic int erst it ial kerat it is [27] .
Hematol ogi c di sorders. Anemia, polycyt hemia rubra vera, Waldenst röm's
macroglobulinemia, and ot her hyperviscosit y syndromes may cause dizziness
and hearing loss.
Hypogl ycemi a. Dizziness or f aint ness occurring a f ew minut es af t er a meal
may be secondary t o react ive hypoglycemia. Pat ient s may also display
adrenergic sympt omat ology.
Hypothyroi di sm. Sympt oms of nervous syst em dysf unct ion are of t en
prominent w it h hypot hyroidism. Hypot hyroidism may be associat ed w it h
episodic vert igo, sensorineural hearing loss, t innit us, and signs of cerebellar
dysf unct ion.
Hyperventi l ati on syndrome. Hypervent ilat ion may account f or episodes of
light headedness of t en associat ed w it h circumoral and digit al parest hesias.
Rapid low ering of Pco2 reduces cerebral blood f low and may cause
dizziness, conf usion, and rarely seizures, even in t he absence of hypoxemia.
Mul ti pl e sensory def i ci ts. Dizziness in older pat ient s may result f rom a
combinat ion of sensory def icit s, including visual impairment , propriocept ive
loss due t o a polyneuropat hy, vest ibular dysf unct ion, and cervical
spondylosis. Dizziness is especially prominent during ambulat ion, part icularly
w hen t urning corners.
Drugs. Vesti bul ar toxi ci ty may be transi ent or permanent, and may be
associ ated wi th symptoms of cochl ear toxi ci ty. Dizziness is a common side
eff ect of many drugs, including analgesics, ant iarrhyt hmics, cyt ot oxic drugs,
ant i-inf lammat ory drugs, aminoglycoside ant ibiot ics (especially gent amycin),
loop diuret ics, aspirin, sedat ives, and ant iconvulsant s. O verdoses of
phenyt oin may cause dizziness and nyst agmus.
O cul ar di sorders. Vert igo and dizziness may occur in associat ion w it h
glaucoma, ext raocular muscle paresis, use of st rong correct ive lenses, and
ref ract ive abnormalit ies.
Mal de debarquement (mal de mer). This condit ion ref ers t o sensat ions of
mot ion, rocking and sw aying, t hat are commonly experienced w it h sea t ravel
and persist in some individuals on ret urn t o land f or w eeks, mont hs, or even
years [23, 81] . Mal de debarquement may also occur af t er air and car t ravel.
Pat ient s w it h mal de debarquement syndrome lack vert igo, nausea, or
vomit ing.
Psychi atri c di sorders (psychogeni c di zzi ness). Subject ive dizziness or
giddiness may occur w it h anxiet y, panic at t acks, mood, somat of orm, and
dissociat ive disorders, claust rophobia, agoraphobia, and ot her psychiat ric
dist urbances, including schizophrenia. A special f orm of psychogenic vert igo,
t hought t o be unrelat ed t o panic at t acks, is phobic post ural vert igo primarily
described among pat ient s w it h obsessive-compulsive personalit y [16, 19] .
Phobic post ural vert igo has six charact erist ic f eat ures [16] .
1. Dizziness and a subject ive dist urbance of balance occur w hile st anding or
w alking despit e normal clinical balance t est s (e. g. , t andem w alking,
balancing on one f oot ).
2. Fluct uat ing unst eadiness in episodes last ing seconds t o minut es or
moment ary percept ion of illusory body pert urbat ions is not iced.
3. Alt hough t he at t acks can occur spont aneously, t here is usually a
percept ual st imulus (e. g. , bridge, st aircase, empt y room) or social
sit uat ion (e. g. , depart ment st ore, rest aurant , crow d) f rom w hich pat ient s
have diff icult y w it hdraw ing and w hich t hey recognize as a provoking
f act or.
4. Anxiet y and dist ressing veget at ive sympt oms occur during or af t er t he
vert igo.
5. O bsessive-compulsive t ype personalit y, labile aff ect , and/ or mild
depression are not iced.
6. O nset of t he condit ion f requent ly f ollow s a period of part icular emot ional
st ress, af t er a serious illness, or f ollow ing an organic vest ibular disorder.
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> Table of C ontents > C hapter 12 - C r anial Ner ves IX and X ( The Glos s ophar yngeal and Vagus Ner ves )
Chapter 12
Cranial Nerves IX and X (The Glossopharyngeal
and Vagus Nerves)
Anatomy of Cranial Nerve IX (Glossopharyngeal Nerve)

The gl ossopharyngeal nerve cont ains mot or, sensory, and parasympat het ic
f ibers. The nerve emerges f rom t he post erior lat eral sulcus of t he medulla
oblongat a dorsal t o t he inf erior olive in close relat ion w it h cranial nerve X (t he
vagus nerve) and t he bulbar f ibers of cranial nerve XI (t he spinal accessory
nerve) (Fig. 12-1) [6, 30] . These t hree nerves t hen t ravel t oget her t hrough t he
jugular f oramen. Wit hin or dist al t o t his f oramen, t he glossopharyngeal nerve
w idens at t he superi or and t he petrous gangl i a and t hen descends on t he lat eral
side of t he pharynx, passing bet w een t he int ernal carot id art ery and t he int ernal
jugular vein. The nerve w inds around t he low er border of t he styl opharyngeus
muscl e (w hich it supplies) and t hen penet rat es t he pharyngeal const rict or
muscles t o reach t he base of t he t ongue.
The mot or f ibers originat e f rom t he rost ral nucleus ambiguus and innervat e t he
styl opharyngeus muscl e (a pharyngeal elevat or) and (w it h t he vagus nerve) t he
constri ctor muscl es of the pharynx.
The sensory f i bers carried in t he glossopharyngeal nerve include t ast e aff erent s,
supplying t he post erior t hird of t he t ongue and t he pharynx, and general visceral
aff erent s f rom t he post erior t hird of t he t ongue, t onsillary region, post erior
palat al arch, sof t palat e, nasopharynx, and t ragus of t he ear. By w ay of t he
t ympanic branch of t he glossopharyngeal nerve (Jacobson's nerve), sensat ion is
supplied t o t he t ympanic membrane, eust achian t ube, and t he mast oid region.
Tast e aff erent s and general visceral aff erent f ibers have t heir cell bodies in t he
pet rous ganglion and t erminat e mainly in t he nucleus of t he solit ary t ract (t he
rost ral t erminat ing f ibers convey t ast e, and t he caudal t erminat ing f ibers convey
general visceral sensat ion); ext erocept ive aff erent s have t heir cell bodies in t he
superior and pet rous ganglia and t erminat e in t he spinal nucleus of t he t rigeminal
nerve. The glossopharyngeal nerve also carries chemorecept ive and
barorecept ive aff erent s f rom t he carot id body (chemorecept ors) and carot id
sinus (barorecept ors), respect ively, by w ay of t he caroti d si nus nerve (nerve of
Heri ng).
The parasympatheti c f i bers carried in t he glossopharyngeal nerve originat e in t he
inf erior salivat ory nucleus, locat ed in t he perivent ricular gray mat t er of t he
rost ral medulla, at t he superior pole of t he rost ral nucleus of cranial nerve X.
These parasympat het ic preganglionic f ibers leave t he glossopharyngeal nerve at
t he pet rous ganglion and t ravel by w ay of t he tympani c nerve or Jacobson's
nerve (coursing in t he pet rous bone) and t he l esser superf i ci al petrosal nerve t o
reach t he oti c gangl i on (just below t he f oramen ovale), w here t hey synapse. The
post ganglionic f ibers t hen t ravel by w ay of t he auri cul otemporal branch of t he
t rigeminal nerve, carrying secret ory and vasodilat ory f ibers t o t he paroti d gl and.
Clinical Evaluation of Cranial Nerve IX

Motor Function
St ylopharyngeal f unct ion is diff icult t o assess. Mot or paresis may be negligible
w it h glossopharyngeal nerve lesions, alt hough mild dysphagia may occur and t he
palat al arch may be somew hat low er at rest on t he side of glossopharyngeal
injury. (How ever, t he palat e elevat es symmet rically w it h vocalizat ion. )
FI G URE 12-1 Vent ral view of medulla and cranial nerves I X, X, and XI exit ing
t oget her t hrough t he jugular f oramen. Dorsal root s of C1 t hrough C6 in t he
upper cervical spinal cord are also show n. (From Daube JR, Reagan TJ,
Sandok BA. Medi cal neurosci ences: an approach to anatomy, pathol ogy,
and physi ol ogy by system and l evel s, 2nd ed. Bost on, MA: Lit t le, Brow n,
1986. By permission of Mayo Foundat ion. )
Sensory Function
The int egrit y of t ast e sensat ion may be t est ed over t he post erior t hird of t he
t ongue and is lost ipsilat erally w it h nerve lesions. Sensat ion (pain, sof t t ouch) is
t est ed on t he sof t palat e, post erior t hird of t he t ongue, t onsillary regions, and
pharyngeal w all. These areas may be ipsilat erally anest het ic w it h
glossopharyngeal lesions.
Reflex Function
The pharyngeal or gag ref l ex i s t est ed by st imulat ing t he post erior pharyngeal
w all, t onsillar area, or base of t he t ongue. The response is t ongue ret ract ion
associat ed w it h elevat ion and const rict ion of t he pharyngeal musculat ure. The
pal atal ref l ex consist s of elevat ion of t he sof t palat e and ipsilat eral deviat ion of
t he uvula w it h st imulat ion of t he sof t palat e. The aff erent arcs of t hese ref lexes
probably involve t he glossopharyngeal nerve, w hereas t he eff erent arcs involve
bot h t he glossopharyngeal and vagus nerves. Unilat eral absence of t hese
ref lexes is seen w it h glossopharyngeal nerve lesions.
Autonomic Function
Salivary secret ion (f rom t he parot id gland) may be decreased, absent , or
occasionally increased w it h glossopharyngeal lesions, but t hese changes are
diff icult t o demonst rat e w it hout specialized quant it at ive st udies.
Localization of Lesions Affecting the Glossopharyngeal

Nerve
Lesions aff ect ing t he glossopharyngeal nerve also usually involve t he vagus, and
t heref ore syndromes aff ect ing bot h nerves are much more common t han nerve
lesions occurring in relat ive isolat ion.
Supranuclear lesions, if unilat eral, do not result in any neurologic def icit because
of bilat eral cort icobulbar input t o t he nucleus ambiguus. How ever, bilat eral
cort icobulbar lesions (pseudo-bulbar palsy) result in severe dysphagia [15] along
w it h ot her pseudo-bulbar signs (e. g. , pat hologic laught er and crying, spast ic
t ongue, explosive spast ic dysart hria). Wit h st imulat ion, t he gag ref lex may be
depressed or markedly exaggerat ed, result ing in severe ret ching and even
vomit ing.
Nuclear and Intramedullary Lesions

These lesions include syringobulbia, demyelinat ing disease, vascular disease,
mot or neuron disease, and malignancy. Such lesions commonly involve ot her
cranial nerves, especially t he vagus, and ot her brainst em st ruct ures (e. g. ,
Wallenberg syndrome) and are t heref ore localized by “t he company t hey keep. ”
Extramedullary Lesions
Cerebellopontine Angle Syndrome
The glossopharyngeal nerve may be injured by lesions, especially acoust ic
t umors, occurring in t he cerebellopont ine angle. Here t here may be
glossopharyngeal involvement associat ed w it h t innit us, deaf ness, and vert igo
(cranial nerve VI I I ), f acial sensory abnormalit ies (cranial nerve V), and
occasionally ot her cranial nerve or cerebellar involvement .
Jugular Foramen Syndrome (Vernet's Syndrome)

Lesions at t he jugular f oramen, especially glomus jugulare t umors and basal skull
f ract ures, injure cranial nerves I X, X, and XI , w hich t ravel t hrough t his f oramen.
O t her et iologies include neuroma, met ast asis t o t he skull base, cholest eat oma,
meningioma, inf ect ion, and giant cell art erit is [12] . Vernet 's syndrome consist s of
t he f ollow ing:
1. I psilat eral t rapezius and st ernocleidomast oid paresis and at rophy (cranial
nerve XI )
2. Dysphonia, dysphagia, depressed gag ref lex, and palat al droop on t he
aff ect ed side associat ed w it h homolat eral vocal cord paralysis, loss of t ast e
on t he post erior t hird of t he t ongue on t he involved side, and anest hesia of
t he ipsilat eral post erior t hird of t he t ongue, sof t palat e, uvula, pharynx, and
larynx (cranial nerves I X and X)
3. O f t en dull, unilat eral aching pain localized behind t he ear
O ccipit al condylar f ract ure may cause paralysis of cranial nerves I X and X
[ 34] .
Lesions w ithin the Retropharyngeal and Retroparotid

Space
The glossopharyngeal nerve may be injured in t he ret ropharyngeal or
ret roparot id space by neoplasms (e. g. , nasopharyngeal carcinoma), abscesses,
adenopat hy, aneurysms [33] , t rauma (e. g. , birt h injury [13] ), or surgical
procedures (e. g. , carot id endart erect omy). Result ing syndromes include t he
Collet -Sicard syndrome (aff ect ing cranial nerves I X, X, XI , and XI I ) and Villaret 's
syndrome (aff ect ing cranial nerves I X, X, XI , and XI I , t he sympat het ic chain, and
occasionally cranial nerve VI I ). The glossopharyngeal nerve may rarely be
damaged in isolat ion by ret ropharyngeal or ret roparot id space lesions result ing
in a “pure” glossopharyngeal syndrome (mild dysphagia, depressed gag ref lex,
mild palat al droop, loss of t ast e on t he post erior t hird of t he t ongue,
glossopharyngeal dist ribut ion anest hesia). For example, t raumat ic int ernal
maxillary art ery dissect ion and pseudoaneurysm may present w it h isolat ed
glossopharyngeal nerve palsy [1] .
Glossopharyngeal (Vagoglossopharyngeal) Neuralgia

G lossopharyngeal neuralgia [5, 8, 31 ref ers t o a unilat eral pain (usually st abbing,
sharp, and paroxysmal) locat ed in t he f ield of sensory dist ribut ion of t he
glossopharyngeal or vagus nerves. Pat ient s usually describe an abrupt , severe
pain in t he t hroat or ear t hat last s seconds t o minut es and is of t en t riggered by
chew ing, coughing, t alking, yaw ning, sw allow ing, and eat ing cert ain f oods (e. g. ,
highly spiced f oods). The pain may occasionally be more persist ent and have a
dull aching or burning qualit y. O t her areas (e. g. , larynx, t ongue, t onsils, f ace,
jaw ) may also be aff ect ed.
The at t acks of glossopharyngeal pain may occasionally be associat ed w it h
coughing paroxysms, excessive salivat ion, hoarseness, and, rarely, syncope [10,
31, 36] . O ccasionally, loss of aw areness associat ed w it h clonic jerks of t he
ext remit ies may occur [20] . The syncopal episodes may possibly result f rom
ref lex bradycardia and asyst ole due t o st imulat ion of t he t ract us solit arius and
dorsal mot or nucleus of t he vagus by impulses originat ing in glossopharyngeal
aff erent s.
Vagoglossopharyngeal neuralgia is of t en “idiopat hic” and may be relat ed t o
ephapt ic excit at ion of t he glossopharyngeal and vagus nerves; how ever, lesions
in t he post erior f ossa or anyw here along t he peripheral dist ribut ion of t he
glossopharyngeal nerve (e. g. , t umor, inf ect ion, t rauma) may also cause t he
syndrome. G lossopharyngeal neuralgia w as caused in one pat ient by
compression of t he low er cranial nerves and brainst em by t he displaced lef t
cerebellar t onsil w it h Chiari I malf ormat ion [19] . Mult iple sclerosis is an
ext remely rare et iology f or t his syndrome [26] (unlike it s relat ively common
associat ion w it h t rigeminal neuralgia).
Anatomy of Cranial Nerve X (Vagus Nerve)

The vagus nerve or pneumogastri c nerve cont ains mot or, sensory, and
parasympat het ic nerve f ibers [6, 30] . The six t o eight root let s of t he vagus nerve
emerge f rom t he post erior sulcus of t he lat eral medulla oblongat a dorsal t o t he
inf erior olive in close associat ion w it h t he glossopharyngeal nerve (Fig. 12-1).
These vagal root let s f orm a single t runk t hat leaves t he skull by w ay of t he
jugul ar f oramen in a dural sheat h t hat also cont ains t he spinal accessory nerve.
Wit hin, or just inf erior t o, t he jugular f oramen are t he t w o vagal ganglia: t he
jugul ar (general somat ic aff erent ) and t he nodose (special and general visceral
aff erent ). Bet w een t he t w o ganglia, t he auri cul ar ramus (nerve of Arnol d) of t he
vagus nerve is given off ; t his branch t hen t raverses t he mast oid process and
innervat es t he skin of t he concha of t he ext ernal ear. At t his point t he vagus also
gives off t he meni ngeal ramus, w hich runs t o t he dura mat er of t he post erior
f ossa, and t he pharyngeal ramus, w hich f orms t he pharyngeal plexus w it h t he
glossopharyngeal nerve and sends mot or f ibers t o t he muscles of t he pharynx
and t he sof t palat e (except t he st ylopharyngeus and t ensor veli palat ini
muscles). The superi or l aryngeal nerve arises f rom t he vagus near t he nodose
ganglion and divides int o a predominant ly mot or external ramus (t o t he
cricot hyroid muscle) and an i nternal ramps (w hich pierces t he t hyrohyoid
membrane and sends sensory f ibers t o t he larynx).
I n t he neck, t he vagus nerve proper descends w it hin a sheat h common t o t he
int ernal carot id art ery and t he int ernal jugular vein. Wit hin t he neck, t he vagus
gives off t he cardi ac rami, w hich f ollow t he carot id art eries dow n t o t he aort a
and cont ribut e f ibers t o t he cardiac plexus. At t he root of t he neck, t he recurrent
l aryngeal nerves are given off and pursue diff erent courses on t he t w o sides.
The right recurrent laryngeal nerve bends upw ard behind t he subclavian art ery t o
ascend in t he t racheoesophageal sulcus, w hereas t he lef t recurrent laryngeal
nerve passes beneat h t he aort ic arch t o at t ain t his sulcus. The recurrent
laryngeal nerves t hen divide int o ant erior and post erior rami, w hich supply all of
t he muscles of t he larynx except t he cricot hyroid muscle (supplied by t he
ext ernal ramus of t he superior laryngeal nerve).
The vagus nerve ent ers t he t horax, crossing over t he subclavian art ery on t he
right side and t raveling bet w een t he lef t common carot id and subclavian art eries
on t he lef t side. The right nerve t hen passes dow nw ard near t he brachiocephalic
t runk and t rachea and behind t he right brachiocephalic vein and superior vena
cava t o t he post erior lung root . The lef t nerve t ravels bet w een t he lef t common
carot id and subclavian art ery, passes over t he aort ic arch, and reaches t he lef t
lung root . I n t he post erior mediast inum bot h nerves send f ibers t o t he pulmonary
and esophageal plexuses and t hen ent er t he abdomen by w ay of t he esophageal
opening of t he diaphragm (t he lef t nerve in f ront of t he esophagus, t he right
nerve behind it ). The vagi t erminat e by innervat ing t he abdominal viscera.
The motor f i bers carried in t he vagus nerve arise f rom t he dorsal mot or nucleus
of t he vagus and t he nucleus ambiguus. The dorsal motor nucl eus of the vagus is
sit uat ed on t he f loor of t he f ourt h vent ricle lat eral t o t he hypoglossal nucleus.
This nucleus gives rise t o preganglionic parasympat het ic f ibers t hat innervat e t he
pharynx, esophagus, t rachea, bronchi, lungs, heart , st omach, small int est ine,
ascending and t ransverse colon, liver, and pancreas. The nucl eus ambi guus is
locat ed in t he ret icular f ormat ion of t he medulla medial t o t he spinal t ract and
nucleus of t he t rigeminal nerve. Fibers f rom t his nucleus supply all of t he st riat ed
musculat ure of t he sof t palat e, pharynx, and larynx except t he t ensor veli palat ini
(cranial nerve V) and st ylopharyngeus (cranial nerve I X) muscles. The cort ical
cent ers f or cont rol of vagal mot or f unct ion are locat ed in t he low er precent ral
gyri, w it h supranuclear innervat ion predominant ly crossed but bilat eral.
The sensory f i bers carried in t he vagus nerve have t heir perikarya in t he jugular
and nodose ganglia. Wit hin t he nodose ganglion are cells w hose f ibers carry
taste sensati on f rom t he epiglot t is, hard and sof t palat es, and pharynx. The
axons of t hese ganglion cells t erminat e in t he nucl eus sol i tari us of t he medulla.
G eneral vi sceral sensati ons f rom t he oropharynx, larynx, and linings of t he
t horacic and abdominal viscera have t heir cells of origin in t he nodose ganglion,
w hich also project s t o t he nucl eus sol i tari es (nucleus parasolit arius).
Exterocepti ve sensat ion f rom t he concha of t he ear is carried by t he vagus
(jugular ganglion) t o t erminat e in t he descendi ng (spi nal ) nucl eus of the
tri gemi nal nerve.
Clinical Evaluation of Cranial Nerve X

Motor Function
The st riat ed muscles of t he sof t palat e (except t he t ensor veli palat ini), pharynx,
and larynx are innervat ed by t he vagus nerve. The sof t palat e and uvula are
examined at rest and w it h
phonat ion; w it h phonat ion t he palat e should elevat e symmet rically w it h no uvular
deviat ion. Pharyngeal f unct ion is evaluat ed by observing pharyngeal cont ract ion
during phonat ion and sw allow ing and by not ing t he charact er of t he voice, by
not ing t he ease of respirat ions and cough, and by direct observat ion of laryngeal
movement s during laryngoscopy.
Wit h unilat eral vagal lesions, t here is ipsilat eral f lat t ening of t he palat al arch;
w it h phonat ion, t he ipsilat eral palat e f ails t o elevat e, and t he uvula is ret ract ed
t ow ard t he nonparalyzed side. Dysphagia and art iculat ion dist urbances (a “nasal
t w ang” t o t he voice) may occur, and during phonat ion only t he upper pharynx is
elevat ed. The ipsilat eral vocal cord assumes t he cadaveric posit ion (midw ay
bet w een adduct ion and abduct ion), and alt hough volunt ary coughing may be
impaired, t here is lit t le dyspnea.
Wit h bi l ateral vagal lesions, t he palat e droops bilat erally w it h no palat al
movement , on phonat ion. O n speaking, air escapes f rom t he oral t o t he nasal
cavit y, giving t he voice a “nasal” qualit y. Bilat eral pharyngeal involvement result s
in prof ound dysphagia, more pronounced f or liquids, w hich t end t o be divert ed
int o t he nasal cavit y. The voice is hoarse and w eak, coughing is poor or not
possible, and respirat ion is severely embarrassed.
Sensory Function
Sensory f unct ion of t he vagus nerve cannot be t est ed adequat ely because t he
area of supply overlaps t hat of ot her cranial nerves (e. g. , t he pinna), some
st ruct ures are inaccessible (e. g. , t he meninges), and t here is diff icult y in t est ing
t he epiglot t is f or t ast e f unct ion.
Reflex Function
The aff erent limb of t he pharyngeal ref lex (gag ref lex) runs in t he
glossopharyngeal nerve, and t he eff erent limb runs in t he glossopharyngeal and
vagus nerves. Theref ore, unilat eral vagal lesions depress t he ipsilat eral gag
ref lex by int errupt ing t he eff erent arc.
Localization of Lesions Affecting the Vagus Nerve

Unilat eral cerebral hemispheric lesions (low er precent ral gyrus) rarely cause any
vagal dysf unct ion because t he supranuclear cont rol is bilat eral. Rarely,
dysphagia may occur w it h a unilat eral precent ral lesion [25] . Unilat eral palat al
paralysis w it hout not able w eakness of t he ext remit ies has been described w it h a
cerebral inf arct aff ect ing t he superior segment of t he corona radiat a [17] . The
sit e of t he lesion corresponded t o t he cort icof ugal mot or t ract f rom t he mot or
cort ex t o t he genu of t he int ernal capsule.
Bilat eral upper mot or neuron lesions result in pseudo-bul bar pal sy, in w hich
dysphagia and spast ic dysart hria are prominent . Emot ional incont inence w it h
pat hologic crying is common. The gag ref lex may be depressed or exaggerat ed.
Nuclear Lesions and Lesions Within the Brainstem

Lesions of t he nucleus ambiguus may occur w it h vascular insult s (lat eral
medullary or Wallenberg syndrome), t umors, syringobulbia, mot or neuron
disease, and inf lammat ory disease. Nuclear lesions result in ipsilat eral palat al,
pharyngeal, and laryngeal paralysis t hat is usually associat ed w it h aff ect ion of
ot her cranial nerve nuclei, root s, and long t ract s. When only t he more cephalad
port ion of t he nucleus ambiguus is injured, laryngeal f unct ion is spared
(palat opharyngeal paralysis of Avellis) ow ing t o t he somat ot opic organizat ion of
t his mot or nucleus.
Lesions within the Posterior Fossa

The vagus nerve may also be damaged w here it emerges f rom t he medulla.
Lesions at t his locat ion also usually involve t he glossopharyngeal, spinal
accessory, and hypoglossal nerves and include primary (e. g. , glomus jugulare)
and met ast at ic t umors, inf ect ions (e. g. , meningit is, ot it is), carcinomat ous
meningit is, sarcoidosis, syndrome G uillain-Barré syndrome, and t rauma. The
syndromes t hat occur most commonly include t he f ollow ing:
Syndrome Cranial Nerves Involved
Jugular f oramen syndrome of Vernet I X, X, XI

Schmidt 's syndrome X, XI
Hughlings Jackson syndrome X, XI , XI I
Collet -Sicard syndrome I X, X, XI , XI I
Lesions Affecting the Vagus Nerve Proper

The t runk of t he vagus nerve may be injured in t he neck and t horax by t umors,
aneurysms of t he int ernal carot id art ery, t rauma, and enlarged lymph nodes.
I solat ed vagus nerve paralysis has been described due t o spont aneous int ernal
carot id art ery
dissect ion [27] . These injuries result in complet e ipsilat eral vocal cord paralysis
associat ed w it h unilat eral laryngeal anest hesia.
Lesions of the Superior Laryngeal Nerve

The superior laryngeal nerve may be damaged by t rauma, surgery, or t umor.
Lesions of t his nerve result in f ew clinical f indings because t his branch is
primarily sensory. The cricot hyroid muscle is innervat ed by t his branch, how ever,
and it s involvement may result in mild hoarseness w it h some decrease in voice
st rengt h.
Lesions of the Recurrent Laryngeal Nerve

The recurrent laryngeal nerve is suscept ible t o injury t hroughout it s int rat horacic
course by aneurysms of t he aort ic arch or subclavian art ery, enlarged
t racheobronchial lymph nodes, mediast inal t umors, and operat ive damage (e. g. ,
t hyroidect omy) [14] . The lef t recurrent laryngeal nerve is longer t han t he right
and is t heref ore damaged more of t en. I n up t o one-f ourt h t o one-t hird of cases
of isolat ed recurrent laryngeal palsy, t here is no discoverable cause [4, 16] ;
how ever, w it h t he advent of modern neuroimaging, t he group of pat ient s w it h
idiopat hic vocal cord paralysis should grow smaller [18] . Breast cancer
ext ending behind t he carot id sheat h at t he C6 level may produce a combinat ion
of recurrent laryngeal nerve paralysis, paralysis of t he phrenic and vagal nerves,
and a preganglionic Horner syndrome (Rowl and Payne syndrome) [2, 35] .
Uni l ateral recurrent laryngeal nerve injury result s in hoarseness t hat is of t en
t ransient . A f l acci d dysphoni a [ 9] result s, w it h voice qualit y def ect s of harshness
and breat hiness w it h short phrases, reduced loudness, and mild inhalat ory
st ridor not ed during cont ext ual speech. Palat opharyngeal and art iculat ory
f unct ions are normal. Vow el prolongat ion (“ah… “) may result in di pl ophoni a, or
t w o pit ch levels heard simult aneously, t hought t o be due t o unequal f requency of
vibrat ion bet w een vocal cords [9] . Wit h unilat eral recurrent laryngeal nerve
palsy, unilat eral paralysis of all laryngeal muscles (except t he cricot hyroid, w hich
is innervat ed by t he superior laryngeal nerve) result s. O n laryngoscopy, t he
paralyzed vocal cord lies near t he midline, w hereas t he normal cord comes
across t o meet t he midline w hen phonat ion is at t empt ed. The adduct or muscles
of t he larynx t end t o be aff ect ed f irst w it h peripheral recurrent laryngeal nerve
injury (Semon's law ).
Bilat eral recurrent laryngeal palsies [7, 11, 24 are usually not ed af t er
t hyroidect omy but may also be seen w it h polyneuropat hy or carcinoma of t he
t hyroid or esophagus and are alw ays sympt omat ic. Bilat eral abduct ion paralysis
may produce severe approximat ion of t he vocal cords associat ed w it h airw ay
limit at ion, w hich of t en necessit at es t racheost omy. I nspirat ory st ridor and
dyspnea on exert ion are common. The voice is w eak but remains clear; w hen t he
t w o vocal cords cannot be brought int o cont act , aphonia result s. Pat ient s w it h
spinocerebellar at axia t ype I of t en have vocal cord abduct or paralysis
associat ed w it h mild dysphagia and noct urnal st ridor [32] . Tw o brot hers w it h
adult -onset f amilial laryngeal abduct or paralysis, cerebellar at axia, and pure
mot or neuropat hy have been described [3] . They present ed w it h lat e-onset
cerebellar at axia and severe dysphonia, t he lat t er due t o severe laryngeal
abduct or paralysis. Neurophysiologic st udies show ed a pure mot or neuropat hy.
Acut e vocal cord paralysis may occur in pat ient s w it h heredit ary neuropat hy w it h
liabilit y t o pressure palsies [28] . A pat ient w it h t his ent it y developed t he acut e
onset of aphonia due t o recurrent laryngeal palsy t riggered by sleeping in t he
prone posit ion.
Syncope from Glossopharyngeal or Vagal Metastasis

Syncope w it h or w it hout pain may be t he only sympt om of met ast at ic involvement
of t he glossopharyngeal or vagus nerve [23, 29] . The condit ion commonly
accompanies head and neck t umors and is part icularly likely w hen t he t umor
recurs af t er init ial t reat ment , especially af t er radical neck dissect ion. The t umor
aff ect s t he carot id sinus nerve f ibers on t he carot id art ery or t he more proximal
nerve f ibers at t he skull base. Aff ect ed pat ient s complain of severe paroxysms of
pain last ing f rom a f ew minut es t o 30 minut es. The pain may be in t he neck, t he
ear, or t he side of t he head, and is accompanied by syncope, t he result of
sudden hypot ension. The hypot ension is somet imes, but not alw ays,
accompanied by bradycardia and occasionally by cardiac arrest . The disorder
may occur once every f ew w eeks t o several t imes per day. This disorder is
probably a result of aberrant discharge of t he damaged nerve, w hich st imulat es
brain nuclei t o inhibit sympat het ic vasoconst rict or t one. Somet imes t he condit ion
resolves spont aneously as t he t umor progresses t o complet ely dest roy t he nerve
[ 29] . An aneurysm of t he ext racranial int ernal carot id art ery may rarely present
w it h t he syndrome of glossopharyngeal pain and
syncope [22] . Anot her cause of syncope relat ed t o met ast at ic disease is swal l ow
syncope [ 21] . This rare syndrome can result f rom t he involvement of
glossopharyngeal or vagal aff erent s or f rom met ast ases t o t he esophagus. The
pat ient suddenly loses consciousness during a hard sw allow, usually because of
int ense bradycardia caused by st imulat ion of barorecept or nerves [21] .
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abduct or paralysis, cerebellar at axia, and pure mot or neuropat hy. Neurol ogy
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t ransient cranial mononeuropat hy. Br Med J 1972; 4: 259–261.
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8. Chaw la JC, Falconer MA. G lossopharyngeal and vagal neuralgia. Br Med J

1967; 3: 529–531.
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motor speech di sorders. Phi l adel phi a, PA: WB Saunders, 1975.
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cardiac syncope. Neurosurgery 1995; 36: 58–63.
11. G orman JB, Woodw ard FD. Bilat eral paralysis of t he vocal cords:
management of t w ent y-f ive cases. South Med J 1965; 58: 34.
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Ann Neurol 1998; 50: 1862–1864.
13. G reenberg SJ, Kandt RS, D'Souza BJ. Birt h injury induced
glossopharyngeal paresis. Neurol ogy 1987; 37: 533–535.
14. Haw e P, Lot hian KR. Recurrent laryngeal nerve injury during
t hyroidect omy. Surg G ynecol O bstet 1960; 110: 488.
15. Horner J, Bouyer FG , Albert s MJ, et al. Dysphagia f ollow ing brain-st em
st roke. Clinical correlat es and out come. Arch Neurol 1991; 48: 1170–1173.
16. Huppler EG , Schmidt HW, Devine KD, et al. Ult imat e out come of pat ient s
w it h vocal cord paralysis of undet ermined cause. Am Rev Tuberc Pul m Di s
1956; 73: 52.
17. I w at a M. Unilat eral palat al paralysis caused by lesion in t he cort icobulbar

t ract . Arch Neurol 1984; 41: 782–784.
18. Jacobs CJ, Harnsberger HR, Luf kin RB, et al. Vagal neuropat hy:
evaluat ion w it h CT and MR imaging. Radi ol ogy 1987; 164: 97–102.
19. Kanpolat Y, Unlu A, Savas A, et al. Chiari t ype I malf ormat ion presenti ng
as glossopharyngeal neuralgia: case report . Neurosurgery 2001; 48: 226–228.
20. Lagerlund TD, Harper CM Jr, Sharbrough FW, et al. An

elect roencephalographic st udy of glossopharyngeal neuralgia w it h syncope.
Arch Neurol 1988; 45: 472–475.
21. Levin B, Posner JB. Sw allow syncope: report of a case and review of t he
lit erat ure. Neurol ogy 1972; 22: 1086–1093.
22. Lim Y-M, Lee S-A, Kim D-K, et al. Aneurysm of t he ext racranial int ernal
carot id art ery present ing as t he syndrome of glossopharyngeal pain and
syncope. J Neurol Neurosurg Psychi atry 2002; 73: 87–88.
23. MacDonald DR, St rong E, Nelson S, et al. Syncope f rom head and neck
cancer. J Neurooncol 1983; 1: 257–267.
24. Manski TJ, Wood MD, Dunsker SB. Bilat eral vocal cord paralysis
f ollow ing ant erior cervical discect omy and f usion. Case report . J Neurosurg
1998; 89: 839–843.
25. Meadow s JC. Dysphagia in unilat eral cerebral lesions. J Neurol

26. Minagar A, Sheremat a WA. G lossopharyngeal neuralgia and MS.

Neurol ogy 2000; 54: 1368–1370.
27. Moussout t as M, Tuhrim S. Spont aneous int ernal carot id art ery dissect ion
w it h isolat ed vagus nerve def icit . Neurol ogy 1998; 51: 317–318.
28. O hkoshi N, Kohno Y, Hayashi A, et al. Acut e vocal cord paralysis in

heredit ary neuropat hy w it h liabilit y t o pressure palsies. Neurol ogy
2001; 56: 1415.
29. O nrot J, Wiley RG , Fogo A, et al. Neck t umour w it h syncope due t o

paroxysmal sympat het ic w it hdraw al. J Neurol Neurosurg Psychi atry
1987; 50: 1063–1066.
30. Peele TL. The neuroanatomi c basi s f or cl i ni cal neurol ogy, 3rd ed. New
York: McG raw -Hill, 1977: 216–224.
31. Rusht on JG , St evens JC, Miller RH. G lossopharyngeal

(vagoglossopharyngeal) neuralgia-a st udy of 217 cases. Arch Neurol
1981; 38: 201–205.
32. Shiojiri T, Sunemi T, Mat sunaga T, et al. Vocal cord abduct or paralysis in
spinocerebellar at axia t ype 1. J Neurol Neurosurg Psychi atry 1999; 67: 695.
33. St urzenegger M, Huber P. Cranial nerve palsies in spont aneous carot id

art ery dissect ion. J Neurol Neurosurg Psychi atry 1993; 56: 1191–1199.
34. Urculo E, Arrazola M, Arrazola M Jr, et al. Delayed glossopharyngeal and

vagus nerve paralysis f ollow ing occipit al condyle f ract ure. J Neurosurg
1996; 84: 522–525.
35. Vaghadia H, Spit t le M. New ly recognized syndrome in t he neck. J Royal

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glossopharyngeal neuralgia. Arch Neurol 1986; 43: 90–92.
> Table of C ontents > C hapter 13 - C r anial Ner ve XI ( The S pinal Ac c es s or y Ner ve)
Chapter 13
Cranial Nerve XI (The Spinal Accessory Nerve)
Anatomy of the Cranial Nerve XI (Spinal Accessory

Nerve)
This purely mot or nerve (Fig. 13-1) [8, 46] originat es part ly f rom t he medulla
(cranial part or int ernal ramus) and part ly f rom t he spinal cord (spinal root or
ext ernal ramus). The cranial root arises f rom cells sit uat ed in t he caudal part of
t he nucleus ambiguus of t he medulla. I t s f ibers emerge f rom t he lat eral medulla
below t he root s of t he vagus. The spinal part arises f rom a column of cells (t he
accessory nucleus) t hat ext ends f rom t he f irst t o t he sixt h cervical cord
segment s in t he dorsolat eral part of t he vent ral horn of t he spinal cord. The
column of cells and low er mot or neuron root s of t he spinal accessory nerve are
somat ot opically arranged: cord levels C1 and C2 innervat e predominant ly t he
ipsilat eral st ernocleidomast oid muscle, and levels C3 and C4 innervat e primarily
t he ipsilat eral t rapezius [37] . These spinal f ibers pass t hrough t he lat eral
f uniculus, leaving t he cord bet w een t he dent at e ligament and t he dorsal spinal
root s. They t hen unit e t o f orm t he spinal part and ascend in t he subarachnoid
space ent ering t he skull t hrough t he f oramen magnum.
The cranial and spinal root s unit e and exit f rom t he skull t hrough t he jugular
f oramen. The cranial port ion t hen branches off as t he int ernal ramus and joins
t he vagus nerve t o supply t he pharynx and larynx. The ext ernal ramus ent ers t he
neck bet w een t he int ernal carot id art ery and t he int ernal jugular vein. I t t hen
penet rat es and supplies t he st ernocleidomast oid muscle and emerges near t he
middle of t he post erior border of t he muscle. The ramus t hen crosses t he
post erior cervical t riangle t o supply t he t rapezius muscle. I n it s course t he nerve
receives branches f rom t he second, t hird, and f ourt h cervical nerves. The
innervat ion of t he st ernocleidomast oid muscle may be more complex t han is
usually quot ed. For example, t here w as residual st ernocleidomast oid movement
in 9 out of 15 cases w here a division of t he spinal component s of t he accessory
nerve and t he upper cervical mot or root s w as made as t reat ment f or spasmodic
t ort icollis [21] . I t is post ulat ed t hat t his residual innervat ion w as likely of vagal
origin.
The supranuclear innervat ion of t he t rapezius and st ernocleidomast oid muscles
probably originat es in t he low er precent ral gyrus. The cort icobulbar f ibers t o t he
t rapezius are crossed, and t hus one cerebral hemisphere supplies t he
cont ralat eral t rapezius muscle. The course of t he f ibers cont rolling t he
st ernocleidomast oid muscle is unknow n, but t he f ibers are t hought t o t erminat e
chief ly in t he i psi l ateral nuclei. Three alt ernat ive pat hw ays f or t his ipsilat eral
innervat ion have been post ulat ed, as f ollow s [19] :
1. The innervat ion may be t ruly ipsilat eral w it h f ibers descending ipsilat erally
f rom hemisphere t o nuclei.
2. The pat hw ay may st art in one hemisphere and cross t he corpus callosum t o
t he opposit e hemisphere, w hich in t urn cont rols movement on t he
cont ralat eral side.
3. A double decussat ion may exist . The pat hw ay t o t he st ernocleidomast oid
muscle may cross f rom t he hemisphere t o t he opposit e pons and t hen ret urn,
below t he f irst cervical level, t o t he side of t he cord ipsilat eral t o t he
hemisphere of origin [5, 25, 39] .
O t hers have suggest ed t hat t he st ernal head of t he st ernocleidomast oid (w hich

t urns t he head t o t he cont ralat eral side) receives bilat eral cort ical innervat ion,
mainly f rom t he ipsilat eral cort ex w it h a double decussat ion, w hereas t he
clavicular
head of t he muscle (w hich t ilt s t he head t o t he ipsilat eral side) appears t o have
a dist inct cort ical represent at ion [14] . These f indings support t he concept t hat
each cerebral hemisphere cont rols muscles t hat result in movement s t ow ard t he
cont ralat eral hemispace rat her t han simply cont rolling t he cont ralat eral muscle
groups [14] . For example, only mild w eakness of t he right st ernocleidomast oid
muscle w as not ed w it h Wada t est ing of t he right carot id art ery; t heref ore,
bilat eral hemispheric innervat ion of t he st ernocleidomast oid must be present
[ 13] . A w eakness of only t he st ernocleidomast oid ipsilat eral t o t he side of t he
carot id inject ion suggest s t hat t he ipsilat eral hemisphere is more involved in t he
cort ical innervat ion of t he ipsilat eral st ernocleidomast oid muscle t han t he
cont ralat eral muscle [13] .
FI G URE 13-1 Anat omy of t he spinal accessory nerve (cranial nerve XI )
DeToledo and David not ed t he f ollow ing [12] :
1. The XI nucleus has a rost ral and a caudal port ion.

2. Analogous t o t he VI I nerve nucleus, t he rost ral port ion receives project ions
f rom bot h cerebral hemispheres, w hereas t he caudal port ion is innervat ed
pref erent ially by t he cont ralat eral hemisphere.
3. The caudal XI nucleus innervat es t he ipsilat eral cleidomast oid and t rapezius
w it h a predominant ly crossed cort iconuclear innervat ion.
4. The rost ral XI nucleus innervat es bot h st ernomast oids. Each rost ral port ion
receives project ions f rom bot h cerebral hemispheres.
Cont rary t o t he long-held view t hat t he represent at ion of t he neck muscles in t he

mot or st rip is close t o t hat of t he f ace, Thompson et al. f ound t hat t he project ion
t o bot h t he ipsilat eral and cont ralat eral st ernocleidomast oid muscles arises f rom
an area of t he cort ex high up on t he cerebral convexit y close t o t he t runk
represent at ion and at a comparable level t o t he sensory innervat ion of t he neck
in t he post cent ral cort ex [54] . The origin of cort icomot or project ions t o t his
muscle lies in a region of t he cort ex locat ed bet w een t he represent at ion of t he
t runk and upper limb. The aut hors not ed t hat t he cort icomot or project ion t o t he
st ernocleidomast oid muscle f ollow s bot h a f ast conduct ing monosynapt ic
cont ralat eral pat hw ay and an ipsilat eral pat hw ay t hat may be disynapt ic [54] .
The cort icobulbar f ibers t o t he st ernocleidomast oid are locat ed in t he brainst em
t egment um, w hereas f ibers t o t he t rapezius are locat ed in t he vent ral brainst em
[ 32] . Thus, a vent ral pont ine lesion can cause supranuclear paresis of t he
t rapezius w it h sparing of t he st ernocleidomast oid muscle.
Clinical Evaluation of Cranial Nerve XI Function
The spinal accessory nerve supplies t w o muscles: t he st ernocleidomast oid and
t he t rapezius.
Stenocleidomastoid M uscle
This muscle f lexes t he head and t urns it f rom side t o side. When one muscle
cont ract s, t he head is draw n t ow ard t he ipsilat eral shoulder and rot at ed so t hat
t he occiput is pulled t ow ard t he side of t he cont ract ing muscle. The right
st ernocleidomast oid
is t hus t est ed by having t he pat ient rot at e his head t o t he lef t against resist ance
w hile t he examiner not es t he muscle's cont ract ion by inspect ion and palpat ion.
Bot h st ernocleidomast oid muscles cont ract ing simult aneously f lex t he head
(t est ed by exert ing pressure on t he pat ient 's f orehead w hile t he pat ient at t empt s
ant erof lexion of t he neck).
Trapezius M uscle
This muscle ret ract s t he head and also elevat es, rot at es, and ret ract s t he
scapula. I t also assist s in raising t he abduct ed arm above t he horizont al. This
muscle is t est ed by having t he pat ient shrug his shoulders against resist ance,
and comparing t he t w o sides by observat ion and palpat ion.
Localization of Lesions Affecting Cranial Nerve XI

Lesions of t he spinal accessory nerve result in paresis and at rophy of t he
st ernocleidomast oid and t he t rapezius muscles. Unilat eral paresis of t he
sternocl ei domastoi d does not aff ect t he posit ion of t he head at rest . There is
w eakness in t urning t he head t o t he opposit e side, and w hen t he pat ient f lexes
t he head, it rot at es slight ly t ow ard t he unaff ect ed side because t he act ion of t he
opposit e st ernocleidomast oid muscle is unopposed. Bilat eral st ernocleidomast oid
paresis causes w eakness of neck f lexion, w it h t he head t ending t o f all backw ard
w hen t he pat ient at t empt s t o st and erect .
Unilat eral trapezi us paresis due t o spinal accessory nerve lesions aff ect s
predominant ly t he upper t rapezius f ibers (t he part not supplied by t he cervical
plexus). The shoulder is low er on t he aff ect ed side at rest , and t he scapula is
displaced dow nw ard and lat erally w it h it s vert ebral border slight ly w inged. There
is paresis of shoulder elevat ion and ret ract ion, and t he pat ient cannot raise t he
arm above t he horizont al af t er it has been abduct ed by t he supraspinat us and
delt oid muscles. Trapezius at rophy of t en develops w it h chronic accessory nerve
injury; rarely, neurogenic hypert rophy of t he t rapezius muscle may develop w it h
accessory nerve injury, perhaps due t o excessive spont aneous muscle act ivit y
[ 40] . Bilat eral t rapezius paresis result s in w eakness of neck ext ension, w it h t he
head t ending t o f all f orw ard w hen t he pat ient at t empt s t o st and erect .
Because t he spinal accessory nerve is a purely mot or nerve (except f or some
propriocept ive aff erent f ibers), nerve lesions do not result in sensory
dist urbance.
I n hemispheric lesions result ing in cont ralat eral hemiplegia, t he t rapezius muscle
on t he side of t he hemiplegia is paret ic. How ever, t he head is t urned away f rom
t he hemiplegic side indicat ing paresis of t he st ernocleidomast oid muscle on t he
side opposit e t he hemiplegia (i. e. , ipsilat eral t o t he cerebral lesion). Focal
seizures, part icularly t hose arising in areas 8 and 9 of t he cerebral cort ex, cause
cont ract ion of t he ipsilat eral st ernocleidomast oid muscle as t he head t urns t o t he
side cont ralat eral t o t he epilept ogenic lesion (adversive seizures). Head t urning
w it hout head t ilt ing, t he most common pat t ern observed, has been explained as
an isolat ed cont ract ion of t he st ernomast oid port ion of t he muscle, w it h less
cont ribut ion f rom t he cleidomast oid port ion, w hich t ilt s t he axis of t he head
f orw ard and t ow ard t he ipsilat eral side w hile exert ing less rot at ional f orce [26] .
Because t he st ernocleidomast oid muscle receives a st rong input f rom t he
ipsilat eral cerebral hemisphere, cort ical, capsular, and high brainst em lesions
aff ect ing cort icobulbar f ibers may result in decreased st rengt h on t he head
t urning aw ay f rom t he side of t he lesion [39, 57] .
Bender et al. suggest t hat t he pat hw ay f or st ernocleidomast oid cont rol crosses
f rom t he hemisphere t o t he opposit e pons and t hen ret urns t o t he side of t he
cord ipsilat eral t o t he hemisphere of origin [5] . G eschw ind point s out t hat t his
second decussat ion may w ell be locat ed in t he decussat ion of t he pyramids and
t hat t he side of st ernocleidomast oid paresis in relat ion t o t he side of t he
hemiplegia may be of localizing signif icance [19] . That is, w hen t he hemiplegic
side is cont ralat eral t o t he paret ic st ernocleidomast oid muscle, a hemispheric
lesion is likely, t he descending pat hw ay being aff ect ed above it s double
decussat ion. O n t he ot her hand, hemiplegia associat ed w it h ipsilat eral (t o t he
hemiplegia) st ernocleidomast oid paresis implies a lesion at or below t he pont ine
level (i. e. , af t er t he f irst decussat ion on t he descending pat hw ay). Thus,
medullary lesions aff ect ing cort icobulbar f ibers may result in decreased st rengt h
on t he head t urning t ow ard t he lesion [39] .
Cases of dissociat ed w eakness of t he st ernocleidomast oid and t rapezius
muscles w it h neurologic lesions have been described, including several
syndromes t hat are of localizing value [37] :
1. Weakness of the trapezi us on one si de associ ated wi th weakness of the

sternocl ei domastoi d on the other si de (di ssoci ated weakness) indicat es an
upper mot or neuron lesion ipsilat eral t o t he w eak st ernocleidomast oid and
above t he oculomot or complex.
2. Weakness of the trapezi us on one si de wi th spari ng of the
sternocl ei domastoi d muscl es indicat es a vent ral brainst em lesion (t he
supranuclear f ibers t o t he t rapezius are vent ral t o t hose t o t he
st ernocleidomast oid), a low er cervical cord lesion (due t o t he somat ot opic
arrangement of t he low er mot or neurons and nuclear cell column of t he
t rapezius being below t hat of t he st ernocleidomast oid), or a low er spinal
accessory root lesion (sparing upper root s t o t he st ernocleidomast oid).
3. Weakness of the sternocl ei domastoi d wi th trapezi us spari ng indicat es a
lesion of t he low er brainst em t egment um (sparing vent ral supranuclear f ibers
t o t he t rapezius) or upper cervical accessory root s (sparing low er cervical
root s t o t he t rapezius).
4. Weakness of the sternocl ei domastoi d and the trapezi us muscl es on the
same si de indicat es a cont ralat eral brainst em lesion, an ipsilat eral high
cervical cord lesion, or an accessory nerve lesion bef ore t he nerve divides
int o it s st ernocleidomast oid and t rapezius branches.
5. Weakness i n one muscl e onl y (st ernocleidomast oid or t rapezius) may occur
w it h lesions of t he accessory nerve dist al t o it s bif urcat ion (e. g. , lesion of
t he branch of t he accessory nerve t o t he t rapezius).
Head-t urning movement s have been analyzed in relat ion t o t he act ions of t he t w o
divisions of t he st ernocleidomast oid muscle: t he st ernomast oid division and t he
cleidomast oid division [26] . The st ernomast oid division runs obliquely and
post eriorly f rom t he st ernum t o insert on t he occiput ; it act s mainly on t he
at lant oaxial joint t o rot at e t he head around a vert ical axis so t hat t he f ace point s
upw ard and out w ard over t he cont ralat eral shoulder. The cleidomast oid division
originat es f rom t he clavicle and runs vert ically t o insert int o t he mast oid; it act s
mainly on t he middle cervical joint s below C4 t o t ilt t he axis of t he head f orw ard
and t ow ard t he ipsilat eral side, exert ing lit t le rot at ional f orce. Cleidomast oid
cont ract ion t hus causes t he f ace t o point dow nw ard t o t he same side. When bot h
divisions are act ivat ed simult aneously, t here is an ipsiversive dow nw ard head t ilt
t oget her w it h a cont raversive rot at ion of t he f ace. I n 12 (75%) of 16 pat ient s
w it h surgically conf irmed lat eralized seizure f oci, t he f ace rot at ed upw ard and
cont raversive t o t he hemisphere of seizure origin, consist ent w it h act ivat ion of
t he ipsilat eral st ernomast oid muscle. O ne pat ient show ed a sust ained, dow nw ard
ipsiversive head t ilt consist ent w it h act ivat ion of t he ipsilat eral cleidomast oid
muscle, and t hree pat ient s had a combined ipsiversive head t ilt and
cont raversive f ace rot at ion. No pat ient exhibit ed ipsiversive upw ard f ace rot at ion
or cont raversive head t ilt ing, as w ould be expect ed if t he cont ralat eral
st ernocleidomast oid w ere act ivat ed. These f indings indicat e t hat hemispheric
seizure f oci act ivat e one or bot h divisions of t he ipsilat eral st ernocleidomast oid
muscle and t hat accurat e lat eralizat ion of t he seizure f ocus is possible only w hen
ict al head deviat ion is assessed in t he cont ext of t he diff erent act ions of t he t w o
divisions [26] .
Nuclear Lesions
These relat ively rare lesions result in paresis w it h prominent at rophy and
f asciculat ions t hat aff ect t he t rapezius and st ernocleidomast oid muscles. The
mot or neurons may be pref erent ially at t acked (e. g. , mot or neuron disease) or
may be involved by int raparenchymal high cervical cord-low medulla lesions
(e. g. , int raparenchymal t umor, syringomyelia). A nuclear localizat ion is suggest ed
by associat ed medullary or upper cervical cord dysf unct ion (see Chapt ers 5 and
15).
Infranuclear Lesions
Lesions Within the Skull and Foramen M agnum
Lesions of t he spinal accessory nerve at t he f oramen magnum and w it hin t he
skull also involve neighboring cranial nerves I X (glossopharyngeal), X (vagus),
and XI I (hypoglossal). Thus, t he t rapezius and st ernocleidomast oid paresis is
associat ed w it h dysphonia and dysphagia, loss of t ast e on t he ipsilat eral
post erior t hird of t he t ongue, ipsilat eral palat al paresis, an ipsilat eral depressed
gag ref lex, ipsilat eral vocal cord paralysis, and ipsilat eral t ongue paresis and
at rophy (t he prot ruded t ongue deviat es t o t he side of t he lesion). A mass lesion
in t his locat ion may also direct ly compress t he upper cervical cord or low er
medulla, result ing in “int ramedullary” dysf unct ion. The most common et iologies
f or spinal accessory nerve involvement w it hin t he skull and f oramen magnum
include ext ramedullary neoplasms, meningit is, and t rauma.
Jugular Foramen Syndrome (Vernet's Syndrome) and

Associated Syndromes
The spinal accessory nerve ent ers t he jugular f oramen accompanied by cranial
nerve I X (glossopharyngeal nerve) and cranial nerve X (vagus nerve). Theref ore,
lesions at t he jugular f oramen (e. g. ,
basal skull f ract ure, t umors, inf ect ions, sarcoidosis) [9, 20, 29, 44, 53 result in a
syndrome (Vernet's syndrome) charact erized by t he f ollow ing:
TABLE 13-1 Syndromes Involving Cranial Nerves IX

through XII
Syndrom e
Nerves Affected Location of Lesion
(Eponym )
Retroparotid space
Collet- Cranial nerves IX, usually; lesion may
Sicard X, XI, XII be intracranial or
extracranial
Cranial nerves IX,

X, XI, XII plus Retroparotid or
Villaret's sympathetic chain; retropharyngeal
VII occasionally space
involved
Usually intracranial
before nerve fibers
Cranial nerves X leave skull;
Schmidt's
and XI occasionally inferior
margin of jugular
foramen
May be
intraparenchymal
Cranial nerves X, (medulla); usually
Jackson's
XI, and XII intracranial before
nerve fibers leave
skull
Cranial nerves X
and XII (cranial
nerve XI and the
Tapia's Usually high in neck
sympathetic chain
occasionally
involved)
Often infiltrative;
Garcin's All cranial nerves arising from base of
(hemibase on one side (often skull (especially
syndrome) incomplete) nasopharyngeal
carcinoma)
1. I psilat eral t rapezius and st ernocleidomast oid paresis and at rophy

2. Dysphonia and dysphagia w it h an absent or depressed gag ref lex and a
palat al droop on t he aff ect ed side; paralysis of t he homolat eral vocal cord
3. Loss of t ast e over t he post erior t hird of t he t ongue on t he involved side
4. Depressed sensat ion (e. g. , anest hesia) on t he post erior t hird of t he t ongue,
sof t palat e, uvula, pharynx, and larynx
Lesions aff ect ing t he spinal accessory nerve just af t er it leaves t he skull (in t he
ret roparot id or ret ropharyngeal space) may also involve cranial nerves I X, X,
and XI I and t he nearby sympat het ic chain in variable combinat ions. The result ing
syndromes vary and may also be seen w it h lesions of mult iple cranial nerves
w it hin t he skull and even w it h int ramedullary lesions. I nvolvement of all f our of
t he low er cranial nerves (I X t hrough XI I ) result s in t he Col l et-Si card syndrome
(all f indings are ipsilat eral t o t he sit e of injury), w hich consist s of t he f ollow ing:
1. Paralysis of t he t rapezius and st ernocleidomast oid (cranial nerve XI )

2. Paralysis of t he vocal cord (cranial nerve X) and pharynx (cranial nerve I X)
3. Hemiparalysis of t he t ongue (cranial nerve XI I )
4. Loss of t ast e on t he post erior t hird of t he t ongue (cranial nerve I X)
5. Hemianest hesia of t he palat e, pharynx, and larynx (cranial nerves I X and X)
A case of Collet -Sicard syndrome has been described associat ed w it h t raumat ic

at las f ract ures and congenit al basilar invaginat ion [24] .
The descript ions of ot her syndromes involving cranial nerves I X t hrough XI I and
t he sympat het ic chain vary w idely in t he lit erat ure; Table 13-1 describes some of
t hese syndromes. Cranial nerves I X, X, XI , and XI I may also be variably involved
w it h neuralgic amyot rophy (Parsonage-Turner syndrome) [47] .
Clinical present at ions vary depending on t he nerves involved. When t he
sympat het ic chain is aff ect ed, an ipsilat eral Horner syndrome (miosis, pt osis,
and anhidrosis) also occurs.
Lesions of the Spinal Accessory Nerve Within the Neck

I solat ed spinal accessory nerve palsy may occur as a complicat ion of surgery or
int ernal jugular vein cannulat ion in t he post erior t riangle of t he neck [15, 23] ,
af t er carot id endart erect omy [15, 52, 58, 59] , coronary art ery bypass surgery
[ 38] , blunt
t rauma t o t he shoulder [3] , at t empt ed hanging [4] , shoulder dislocat ion [45] ,
ot her t rauma [15, 18] , radiat ion t herapy [6, 15, 41] , bee st ing [49] , or af t er
nerve st ret ch (i. e. , quickly t urning t he head w hile t he shoulders are pulled dow n
by heavy hand-held object s) [10, 34] . I n some series, t he nerve w as most
commonly injured by surgical t rauma at t he t ime of lymph node biopsy or t umor
excision f ollow ed by penet rat ing or blunt t rauma [7, 15, 17, 19, 36] . The nerve
may also be injured in t he neck by adenopat hy or neoplasm, and occasionally,
isolat ed unexplained lesions occur w it h spont aneous recovery [16, 31] . Nerve
injury result s in ipsilat eral w eakness of t he st ernocleidomast oid and t rapezius
muscles w it hout aff ect ing ot her cranial nerves. Wit h injuries (e. g. , t ract ion) in t he
post erior cervical t riangle dist al t o t he st ernocleidomast oid muscle, t rapezius
w eakness occurs in isolat ion [11] .
I at rogenic injury t o t he spinal accessory nerve is, t hus, not uncommon during
neck surgery involving t he post erior cervical t riangle, because it s superf icial
course here makes it suscept ible. I n a ret rospect ive review of 111 pat ient s w it h
spinal accessory nerve injury, t he most f requent injury mechanism w as iat rogenic
(103 pat ient s, 93%), and 82 (80%) of t hese injuries involved lymph node biopsies
[ 42] . Eight injuries w ere caused by st ret ch (f ive pat ient s) and lacerat ion (t hree
pat ient s).
Pat ient s may develop manif est at ions of neurovascular compression upon arm
abduct ion, associat ed w it h unilat eral droopy shoulder and t rapezius muscle
w eakness caused by iat rogenic spinal accessory neuropat hies f ollow ing cervical
lymph node biopsies [1] . O ne pat ient developed a cold, numb hand w it h complet e
axillary art ery occlusion w hen his arm w as abduct ed t o 90 degree. Anot her
pat ient complained of parest hesias in digit s 4 and 5 of t he right hand, w orsened
by elevat ion of t he arm, w it h nerve conduct ion f indings of right low er t runk
plexopat hy. These t w o cases demonst rat e t hat unilat eral droopy shoulder
secondary t o t rapezius muscle w eakness may cause compression of t he t horacic
out let st ruct ures [1] .
Weakness of neck extensi on against gravit y w it h or w it hout involvement of neck
f lexion has been called t he f l oppy head syndrome [ 33] , t he dropped head
syndrome [ 22, 51] , or head ptosi s [ 55] . The et iologies f or t his syndrome include
myast henia gravis (w hich of t en aff ect s neck f lexors more t han ext ensors), mot or
neuron disease, chronic inf lammat ory demyelinat ing polyneuropat hy,
syringomyelia, polymyosit is, dermat omyosit is, f ascioscapulohumeral muscular
dyst rophy, carnit ine def iciency, adult -onset nemaline myopat hy, hypot hyroidism,
and a rest rict ive noninf lammat ory myopat hy predominant ly aff ect ing t he cervical
paraspinal muscles, result ing in relat ively isolat ed neck ext ensor w eakness
(i sol ated neck extensor myopathy) [2, 22, 27, 28, 33, 35, 42, 43, 48, 50, 51,
56] . Et iologies of t he f loppy head syndrome are out lined in Table 13-2.
TABLE 13-2 Etiologies of the Floppy Head or Dropped

Head Syndrome
Central
Syringomyelia
Neuropathic
Motor neuron disease
Chronic inflammatory demyelinating polyneuropathy
Post-polio syndrome
Neruomuscular Junction
Myasthenia gravis
Myopathic
Polymyositis
Dermatomyositis
Inclusion body myositis
Fascioscapulohumeral muscular dystrophy
Carnitine deficiency
Adult-onset nemaline myopathy
Mitochondrial myopathy
Unspecified congenital myopathy
Hypothyroid myopathy
Myotonic dystrophy with severe hypothyroidism
Hypokalemic myopathy
Cushing's syndrome
Isolated neck extensor myopathy
Mechanical
Cervical spondylitis
Ankylosing spondylitis
Cervical hyperflexion injury (probably due to bilateral
traction neurapraxia of one or more cervical dorsal
rami)
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> Table of C ontents > C hapter 14 - C r anial Ner ve XII ( The Hypoglos s al Ner ve)
Chapter 14
Cranial Nerve XII (The Hypoglossal Nerve)
Anatomy of Cranial Nerve XII (The Hypoglossal Nerve)

The hypoglossal nerve is t he mot or nerve of t he t ongue [4] . I t s f ibers arise f rom
t he hypogl ossal nucl eus, a longit udinal cell column in t he paramedian medulla
t hat lies beneat h t he hypogl ossal tri gone of t he f loor of t he f ourt h vent ricle. The
column of cells ext ends f rom t he caudalmost medulla oblongat a t o t he medullary-
pont ine junct ion. From t he hypoglossal nucleus, t he nerve f ibers t ravel in a
vent rolat eral direct ion t hrough t he medullary ret icular f ormat ion and medial
port ion of t he inf erior olive, coursing immediat ely lat eral t o t he medial
longit udinal f asciculus, medial lemniscus, and pyramid.
The f ibers of t he hypoglossal nerve emerge f rom t he medulla in t he preolivary
sulcus bet w een t he inf erior olivary complex and t he pyramid as 10 t o 12 root let s
t hat are locat ed medial t o cranial nerves I X (t he glossopharyngeal), X (t he
vagus), and XI (t he spinal accessory). These root let s unit e int o t w o bundles t hat
pass separat ely t hrough t he dura mat er and t he hypogl ossal canal of t he skull.
Af t er leaving t he skull in t he hypoglossal canal (ant erior condylar f oramen), t he
t w o nerve bundles unit e and descend vert ically t hrough t he neck t o t he angle of
t he mandible. During t his course, t he hypoglossal nerve is quit e near t he int ernal
carot id art ery and t he int ernal jugular vein. I n t he neck, t he nerve passes t ow ard
t he hyoid bone and t hen t urns medially t ow ard t he t ongue. I t courses over t he
int ernal and ext ernal carot id art eries and event ually lies beneat h t he digast ric,
st ylohyoid, and mylohyoid muscles. The nerve passes bet w een t he mylohyoid
and hypoglossus muscles and t hen breaks up int o a number of branches (t he
muscul ar or l i ngual branches), w hich supply t he various t ongue muscles.
The descendi ng hypogl ossal ramus, w hich courses dow nw ard t o f orm t he ansa
hypogl ossi , is given off f rom t he hypoglossal nerve proper in t he neck. The ansa
hypoglossi is f ormed by t he descending hypoglossal ramus (CN XI I and C1
cervical root ) and t he descending cervical ramus (C2 and C3 cervical root s).
(The ansa hypoglossi is discussed f urt her in Chapt er 3).
The hypoglossal muscular or lingual branches supply all t he int rinsic muscles of
t he t ongue (longit udinal, t ransverse, and vert ical muscles) and also t he
hyoglossus, st yloglossus, genioglossus, and geniohyoid muscles (ext rinsic
muscles of t he t ongue).
Supranuclear cont rol of t he t ongue [4, 18] is mediat ed by cort icobulbar f ibers
t hat originat e mainly w it hin t he low er port ion of t he precent ral gyrus (perisylvian)
area. The cort icobulbar f ibers cont rolling t he genioglossus muscles are crossed;
t he ot her t ongue muscles appear t o have bilat eral supranuclear cont rol. Cort ico-
hypoglossal f ibers branch off t he main vent ral pyramidal t ract [37] . Cort ical
project ions t o t he hypoglossal nucleus cross t he midline in t he pont omedullary
junct ion and ent er t he hypoglossal nucleus f rom it s lat eral aspect [37] .
Clinical Evaluation of Cranial Nerve XII

The clinical evaluat ion of cranial nerve XI I f unct ion consist s of observat ion of t he
t ongue at rest and w it h prot rusion and assessment of t he st rengt h and rapidit y
of t ongue movement s. Alt hough t he hypoglossal nerve does cont ain some
propriocept ive aff erent s, t he nerve is ot herw ise a purely mot or eff erent nerve,
and t hereby nerve lesions do not result in sensory abnormalit ies.
Unilat eral lesions of t he hypoglossal nerve result in paresis, at rophy, f urrow ing,
f ibrillat ions, and f asciculat ions t hat aff ect t he corresponding half of t he t ongue.
This unilat eral paresis is best demonst rat ed by volunt ary t ongue prot rusion,
during w hich t he t ongue deviat es t o t he side of paresis, mainly because of t he
unopposed act ion of t he normal cont ralat eral genioglossus muscle (assist ed by
t he geniohyoid). Wit h unilat eral lesions, dysart hria and dysphagia are minimal,
but diff icult y w it h manipulat ing f ood in t he mout h is of t en evident .
I t may be possible t o dist inguish bet w een ext rinsic and int rinsic t ongue muscle
w eakness in pat ient s w it h unilat eral hypoglossal palsy [30] . I n a pat ient w it h
mult iple cranial nerve palsies, including a unilat eral hypoglossal nerve palsy,
t ongue prot rusion deviat ed t o t he right [30] . When t he t ongue w as not prot ruded,
how ever, t he pat ient could readily t urn t he t ip of t he t ongue t o t he lef t but not
t he right . The aut hor not ed t hat prot rusion of t he t ongue requires t he act ion of
ext rinsic t ongue muscles, w hereas lat eral movement s of t he nonprot ruded t ongue
are accomplished by int rinsic muscles. Prot rusion in t he pat ient w as
accomplished by t he unopposed act ion of t he normal cont ralat eral genioglossus,
w hereas t he t ongue t ip could not be t urned t o t he side of t he lesion due t o
impairment of cont ract ion of t he ipsilat eral int rinsic muscles (especially t he
superior and inf erior longit udinal muscles) [30] .
Bilat eral low er mot or neuron lesions of t he t ongue result in bilat eral at rophy,
w eakness, and f ibrillat ions of t he t ongue. The t ongue t heref ore cannot be
prot ruded volunt arily. This bilat eral aff ect ion result s in a marked diff icult y w it h
art iculat ion, especially w it h t he pronunciat ion of d and t phonemes. Dysphagia is
prominent , and breat hing diff icult ies may occur w hen t he f laccid t ongue f alls
backw ard t o obst ruct t he pharynx.
Localization of Lesions Affecting Cranial Nerve XII

Lesions of t he cort icobulbar t ract anyw here in it s course f rom t he low er
precent ral gyrus t o t he hypoglossal nuclei may result in t ongue paralysis.
Because supranuclear cont rol of t he genioglossus muscle originat es mainly f rom
t he cont ralat eral cort ex, a lesion of t he cort icobulbar f ibers above t heir
decussat ion may result in w eakness of t he cont ralat eral half of t he t ongue.
Theref ore, w it h an int ernal capsular lesion, t he t ongue may deviat e t ow ard t he
side of t he hemiplegia. A supranuclear lesion is not accompanied by at rophy or
f ibrillat ions of t he t ongue.
I nt errupt ion of t he cort ico-lingual pat hw ay t o t he t ongue is crucial in t he
pat hogenesis of dysart hria f ollow ing st rokes aff ect ing t he int ernal capsule, basis
pont is, or corona radiat a [38] . Sudden isolat ed dysart hria may occur w it h
lacunar inf arct s aff ect ing t he cont ralat eral corona radiat a or int ernal capsule,
w hich int errupt in isolat ion t he cort ico-lingual pat hw ays t o t he t ongue (central
monoparesi s of the tongue) [39] .
Pont ine lesions at t he vent ral paramedian base close t o t he midline aff ect t he
cont ralat eral cort ico-hypoglossal project ions, w hereas lat eral lesions at t he
pont ine base aff ect ipsilat eral project ions [37] . Lesions at t he paramedian dorsal
pont ine base do not involve t he cort ico-hypoglossal project ions. Lesions of t he
dorsolat eral and mediolat eral medulla impair only ipsilat eral cort ico-hypoglossal
project ions [37] . This suggest s t hat t he main decussat ion of supranuclear
project ions t o t he hypoglossal nucleus in t he brainst em is locat ed close t o t he
pont omedullary junct ion [37] . How ever, a pat ient has been described w it h
cont ralat eral glossoplegia due t o a vent romedial lesion of t he upper medulla [6] .
I n t his pat ient w it h cont ralat eral supranuclear glossoplegia, t he lesion w as
locat ed in t he vent romedial part of t he rost ral medulla. This f inding show ed t hat
t he cort ico-hypoglossal project ions in t his pat ient decussat ed at t he upper
medullary level, more caudally t han t he pont omedullary junct ion.
Bilat eral upper mot or neuron aff ect ion of t he cort icobulbar f ibers t o t he
hypoglossal nuclei result s in a paret ic t ongue w it h no at rophy or signs of
denervat ion. Lat eral t ongue movement s are slow and irregular ow ing t o poor
supranuclear cont rol (“spasti c tongue”), and a spast ic dysart hria is evident .
Nuclear Lesions and Intramedullary Cranial Nerve XII

Lesions
Unilat eral lesions of t he hypoglossal nucleus or nerve result in paresis, at rophy,
f urrow ing, f ibrillat ions, and f asciculat ions t hat aff ect t he corresponding half of
t he t ongue. Because of t he close proximit y of t he t w o hypoglossal nuclei, dorsal
medullary lesions (e. g. , mult iple sclerosis, syringobulbia) of t en result in bilat eral
low er mot or neuron lesions of t he t ongue. The nuclei may also be aff ect ed in
mot or neuron disease (amyot rophic lat eral sclerosis) and in poliomyelit is (bulbar
t ype). I solat ed hypoglossal nerve palsy has been report ed in associat ion w it h
inf ect ious mononucleosis, presumably due t o viral inf ect ion
of t he hypoglossal nerve nucleus [9] . I solat ed t ot al t ongue paralysis has been

described as a manif est at ion of t he bilat eral medullary inf arct ion aff ect ing t he
t w o nuclei of cranial nerve XI I [2] .
The hypoglossal nerve may be injured, usually unilat erally, anyw here along it s
course in t he medulla. I nt ramedullary hypoglossal involvement is suggest ed by
t he associat ed aff ect ion of t he medial lemniscus, pyramid, or ot her neighboring
int ramedullary st ruct ures. Processes aff ect ing t he hypoglossal nerve in it s
int ramedullary course include t umor, demyelinat ing disease, syringobulbia, and
vascular insult . A rare but charact erist ic syndrome t hat aff ect s t he hypoglossal
nerve in it s int ramedullary course is t he medi al medul l ary syndrome (Dejeri ne's
anteri or bul bar syndrome). This syndrome result s f rom occlusion of t he ant erior
spinal art ery or it s parent vert ebral art ery. The ant erior spinal art ery supplies
t he ipsilat eral pyramid, medial lemniscus, and hypoglossal nerve; it s occlusion
t heref ore result s in t hree main signs:
1. I psilat eral paresis, at rophy, and f ibrillat ions of t he t ongue (due t o aff ect ion
of cranial nerve XI I ). The prot ruded t ongue deviat es t ow ard t he lesion (aw ay
f rom t he hemiplegia).
2. Cont ralat eral hemiplegia (due t o involvement of t he pyramid) w it h sparing of
t he f ace.
3. Cont ralat eral loss of posit ion and vibrat ory sensat ion (due t o involvement of
t he medial lemniscus). Because t he more dorsolat eral spinot halamic t ract is
unaff ect ed, pain and t emperat ure sensat ions are spared.
This medial medullary syndrome may occur bilat erally, result ing in quadriplegia
(w it h f acial sparing), bilat eral low er mot or neuron lesions of t he t ongue, and a
complet e loss of posit ion and vibrat ory sensat ion aff ect ing all f our ext remit ies
[ 21] .
Because t he hypoglossal f ibers run somew hat lat erally t o t he medial lemniscus
and pyramid, t hey are occasionally spared in cases of ant erior spinal art ery
occlusion.
Peripheral Lesions of Cranial Nerve XII

Cranial nerve XI I has a close spat ial relat ionship w it h cranial nerves I X
(glossopharyngeal), X (vagus), and XI (spinal accessory) in t he post erior cranial
f ossa and as it leaves t he skull in t he hypoglossal canal. A basilar skull lesion
(e. g. , t umor or t rauma) [32, 40] may involve t he t w elf t h cranial nerve alone,
producing an isolat ed cranial nerve XI I low er mot or neuron lesion; f requent ly, t he
ot her low er cranial nerves (I X, X, and XI ) are variably involved as w ell. When all
f our of t hese nerves are damaged (e. g. , by a skull f ract ure t hrough t he
hypoglossal canal and jugular f oramen), a Col l et-Si card syndrome result s,
consist ing of t he f ollow ing signs:
1. Paralysis of t he t rapezius and st ernocleidomast oid muscles (cranial nerve XI )

2. Paralysis of t he vocal cord (cranial nerve X) and pharynx (cranial nerve I X)
3. Hemiparalysis of t he t ongue (cranial nerve XI I )
4. Loss of t ast e on t he post erior t hird of t he t ongue (cranial nerve I X)
5. Hemianest hesia of t he palat e, pharynx, and larynx (cranial nerves I X and X)
O t her mult iple low er cranial nerve palsy syndromes may occur w it h lesions in t he
post erior cranial f ossa, in t he skull, in t he ret ropharyngeal or ret rost yloid space,
or in t he neck (see Chapt er 13). Wit h neck lesions, t he cervical sympat het ic
chain may be involved, result ing in an ipsilat eral Horner syndrome (miosis,
anhidrosis, and pt osis). O t her syndromes include t he Collet -Sicard, Villaret 's,
Jackson's, Tapia's, and G arcin's syndromes (see Table 13-1). I solat ed
hypoglossal nerve palsy has been described due t o compression by a kinked
vert ebral art ery (hypoglossal-vert ebral ent rapment syndrome) [31] . Skull
met ast ases t o t he clivus may cause bilat eral hypoglossal nerve palsies [28] .
Combined abducens nerve and hypoglossal nerve palsies are rare. This is of t en
an ominous combinat ion as may be seen w it h nasopharyngeal carcinoma
(G odtf redsen's syndrome) and w it h ot her clival lesions, especially t umors (t hree-
f ourt hs of w hich are malignant ) [16] . Alt hough t he combinat ion of abducens nerve
palsy w it h a hypoglossal nerve palsy usually localizes t he pat hologic process t o
t he clivus, low er brainst em lesions and subarachnoid processes (e. g. ,
cyst icercal meningit is) may also cause t his unusual dual cranial nerve impairment
[ 16] .
Lesions, usually t umors or chronic inf lammat ory lesions, of t he occipit al condyle
may cause occipit al pain associat ed w it h an ipsilat eral hypoglossal nerve injury
(occi pi tal condyl e syndrome) [5, 10, 23] . These pat ient s complain of cont inuous,
severe, localized unilat eral occipit al pain made w orse by neck f lexion and of t en
associat ed w it h neck st iff ness. Rot at ing t he head t ow ard t he side of t he pain
of t en relieves t he discomf ort , w hereas head rot at ion t o t he nonpainf ul side or
suboccipit al palpat ion is unbearable [23] . The pain occasionally radiat es
ant eriorly t ow ard t he ipsilat eral t emporal area or eye. About half of t he pat ient s
complain of dysart hria, dysphagia, or bot h, specif ically relat ed t o diff icult y in
moving t he t ongue. O n examinat ion, pat ient s hold
t heir neck st iff ly and are of t en t ender t o palpat ion over t he occipit al area on t he
involved side. The ipsilat eral t ongue is w eak and at rophic and occasionally
f asciculat ions are evident on t he involved side. The t ongue, w hen prot ruded, w ill
deviat e t o t he involved side. O ccipit al condylar f ract ure may also cause
unilat eral or bilat eral hypoglossal nerve palsies [19] .
The hypoglossal nerve may be injured in isolat ion in t he neck or in it s more dist al
course near t he t ongue. This result s in an ipsilat eral low er mot or neuron t ype of
paresis of half of t he t ongue. The causes of t his peripheral involvement include
carot id aneurysms, aneurysms of a persist ent hypoglossal art ery, vascular
ent rapment , spont aneous dissect ion of t he ext racranial int ernal carot id art ery,
local inf ect ions, t uberculosis of t he at lant oaxial joint , rheumat oid art hrit is,
surgical (e. g. , carot id endart erect omy) or accident al t rauma, birt h injuries, neck
radiat ion, and t umors of t he ret roparot id or ret ropharyngeal spaces, neck,
salivary glands, and base of t he t ongue [1, 3, 11, 13, 20, 22, 25, 26, 29, 33,
35] . Deep cervical lymphadenit is or ot her inf ect ions, including ost eomyelit is,
meningit is, or viral diseases, may also cause hypoglossal palsies [34] . Unilat eral
or bilat eral hypoglossal neuropat hy may occur in pat ient s w it h heredit ary
neuropat hy w it h liabilit y t o pressure palsy [7, 42] .
I n a st udy of 100 cases of hypoglossal palsy, one-t hird of t he pat ient s show ed
bilat eral involvement [15] . Tumors, predominant ly malignant t umors, produced
nearly half of t he cases w it h met ast ases, chordoma, nasopharyngeal carcinoma,
and lymphoma t he most common t ypes. Trauma (e. g. , gunshot w ounds) w as t he
second most common cause. O t her et iologies included st roke, syndrome
G uillain-Barré syndrome, inf ect ion, neck surgery, Chiari malf ormat ion, mult iple
sclerosis, and hyst eria [15] .
Af t er hypoglossal nerve injury f rom carot id endart erect omy, pat ient s may
occasionally develop increasingly severe dysart hria and dysphagia beginning
several mont hs af t er t he surgery [41] . Elect rophysiologic st udies have revealed
abnormal coact ivat ion of t he genioglossus and st yloglossus muscles on t he
aff ect ed side in t hese pat ient s, suggest ing aberrant reinnervat ion. When
aberrant reinnervat ion occurs, t he t ongue no longer moves in a coordinat ed
manner, and signif icant dysart hria ensues.
Abnormal Tongue M ovements

Various movement disorders may aff ect t he t ongue, including drug-induced oral-
buccal-lingual dyskinesia, at het osis, palat al myoclonus (rhyt hmic synchronous
t ongue movement s) [24] , and t remor. Choreif orm movement s of t he t ongue may
result in bizarre lingual movement s and an inabilit y t o keep t he t ongue prot ruded
on command (trombone tongue). G al l opi ng tongue ref ers t o an episodic,
rhyt hmic involunt ary movement of t he t ongue t hat has been described af t er head
and neck t rauma, consist ing of 3 per second w aves t hat began as post erior
midline f ocal t ongue cont ract ions [14] . These movement s last ed approximat ely
10 seconds in each episode and w ere not accompanied by ot her body
movement s or elect roencephalographic abnormalit ies. They w ere t hought t o be
of brainst em, perhaps pont ine, origin [14] . Episodic t ongue movement s similar t o
t hese have been described in pat ient s w it h chronic epilepsy, w ho had isolat ed
post erior w ave-like t ongue movement s t hat occurred t w o t o t hree t imes per
second f or up t o 30 seconds and t hat coincided w it h desynchronizat ion of t he
elect roencephalogram–Elect roencephalogram (EEG ) (t hought t o be “subcort ical
seizures”) [12] . Cont inuous undulat ing movement s of t he t ongue have been
described years af t er radiat ion t herapy f or nasopharyngeal carcinoma [33] .
Conti nuous l i ngual myocl onus has been described af t er head injury (EEG
normal) and is t hought t o be a f orm of branchial myoclonus w it hout palat al
myoclonus [36] . Abnormal post uring and movement of t he t ongue (lingual
pseudoat het osis), presumably due t o lingual deaff erent at ion, may occur w it h t he
neck-t ongue syndrome (see Chapt er 9) [27] .
Dysarthria
Dysarthri a ref ers t o impaired speech due t o abnormal neuromuscular cont rol and
is manif est by abnormalit ies of art iculat ion, respirat ion, prosody, resonance of
voice, and phonat ion. Mot or speech disorders may result f rom dysf unct ion at t he
upper mot or neuron, low er mot or neuron, cerebellar, ext rapyramidal, or muscular
level, w it h various charact erist ics of t he dysart hria being of localizing value [8] .
The evaluat ion of mot or speech requires t he assessment of t hree speech
act ivit ies [8] :
1. A sample of cont ext ual speech, including oral reading of a st andard

paragraph and evaluat ion of spont aneous speech
2. Vow el prolongat ion (ah…)
3. Alt ernat e mot ion rat e of t he lips, t ongue, and mandible (diadochokinesis),
w hich is t est ed by having t he pat ient repeat puh (labial), tuh (lingual), and
kuh (gut t ural or post erior aspect of t he t ongue) rapidly and evenly
For example, an organic voice t remor (laryngeal t remor) may or may not be
not ed w it h
cont ext ual speech but may be brought out by vow el prolongat ion, during w hich
oscillat ions of t he voice are evident , at t imes result ing in speech arrest . Spast ic
dysart hria (f rom bilat eral upper mot or neuron lesions) has a harsh, st rained, or
st rangled qualit y and slow rat e during cont ext ual speech, w it h slow, regular rat e
during alt ernat e mot ion t est ing and st rained harshness w it h low pit ch in
at t empt ing vow el prolongat ion. When mult iple levels of t he neuraxis are aff ect ed,
mot or speech abnormalit ies are mixed (e. g. , mixed f laccid and spast ic dysart hria
w it h amyot rophic lat eral sclerosis; mixed spast ic and at axic dysart hria w it h
mult iple sclerosis; and mixed spast ic, at axic, and hypokinet ic dysart hria w it h
Wilson's disease). Pat ient s w it h progressive supranuclear palsy may have
predominant ly spast ic, hypokinet ic, and at axic component s, or a mixed
dysart hria w it h a combinat ion of spast ic, hypokinet ic, and at axic component s
[ 17] . The various t ypes of dysart hria and t heir charact erist ics are described in
Table 14-1.
TABLE 14-1 M otor Speech Disorders
Contextual Vowel
Type of Dysarthria
Speech Prolongation
Diplophonia,
harshness.
Flaccid dysphonia breathiness,
(unilateral vocal cord short phrases, Diplophonia
paralysis) red. loudness,
mild inhalation
stridor
Breathiness,
red. loudness, Breathiness,
Flaccid dysarthria
hypernasality, red.
(multiple cranial nerve
stridor, short loudness,
palsies)
phrases, vowel red. duration
prolongation
Slow rate:
harsh,
strained,
strangled; Strained
Spastic dysarthria imprecise harshness,
(bilateral upper motor consonants; red.
neuron lesion) mono and low duration, low
pitch; grunts pitch
at end of
phrases;
hypernasality
Irregular,
seemingly
random
breakdowns in
Ataxic dysarthria articulatory

(cerebellar lesion) precision:
vowel
distortions;
excess and
equal stress.
Short rushes
of speech:
accelerated
rate, Harshness,
Hypokinetic dysarthria
monopitch, breathiness,
(parkinsonism)
reduced and low pitch
monoloudness,
inappropriate
silences
Variable rate,
inappropriate
Inability to
silences,
sustain
imprecise
phonation
consonants,
due to
prolonged
laryngeal
Hyperkinetic dysarthria phonemes,
and
(chorea) prolonged
articulatory
intervals interruptions,
between voice
words, strained and
irregular harsh
articulatory
breakdowns
Intermittent
Breathiness;
voice arrests,
harshness
excess
with
loudness
strained,
Hyperkinetic dysarthria variations,
strangled
(laryngeal dystonia) distorted
component;
vowels,
inability to
imprecise
sustain
consonants,
phonation
reduced rates
Continuously
Hyperkinetic dysarthria Distortion of
changing
(articulatory dystonia) articulation
vowel quality
Brings out
tremor;
arrests voice
indicating
rhythmic
Rhythmic
Hyperkinetic dysarthria glottic
alterations in
(organic voice tremor) closure
pitch loudness
(such
closures
accompanied
by strained,
harsh voice)
Hyperkinetic dysarthria Almost Momentary

(palatopharyngolaryngeal impossible to interruptions
myoclonus) detect in phonation
Paroxysmal automatic or uncont

Hyperkinetic dysarthria
grunting, barking, coughing, thr
(Gilles de la Tourette)
whistling, etc.; occasional copro
Red. = reduced.
Adapted from Darley FL, Aronson AF, Brown JR. Audio sem
speech pathology—Motor speech disorders. Philadelphia: S
1975, with permission.
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20. Macedo TF, G ow PJ, Heap SW, et al. Bilat eral hypoglossal nerve palsy
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> Table of C ontents > C hapter 15 - B r ains tem
Chapter 15
Brainstem
M edulla Oblongata
Anatomy of the Medulla
The medulla oblongat a or myel encephal on is t he most caudal port ion of t he
brainst em (Fig. 15-1) and ext ends f rom t he caudal border of t he pons t o a point
just rost ral t o t he point of emergence of t he f irst spinal nerve root s. The junct ion
of t he medulla oblongat a and spinal cord is at t he level of t he f oramen magnum.
The cross-sect ional anat omy at a midmedullary level is illust rat ed in Figure 15-2.
Wit hin t he subst ance of t he medulla cert ain cranial nerve nuclei and root s are
sit uat ed[ 19] . The hypogl ossal nucl eus (cranial nerve XI I ) is locat ed near t he
vent rolat eral port ion of t he cent ral canal under an eminence called t he
hypogl ossal tri gone. The nerve root s of t he hypoglossal nerve pass vent rally and
emerge f rom t he medulla in t he ant erior lat eral sulcus bet w een t he pyrami ds and
t he ol i ve ( i nf eri or ol i vary promi nence). The nucl eus ambi guus (cranial nerves
I X, X, and bulbar XI ) is locat ed w it hin t he medullary ret icular f ormat ion
vent romedial t o t he nucl eus and spi nal tract of the tri gemi nal nerve (cranial
nerves V, VI I , I X, and X). The dorsal motor nucl eus of the vagus (cranial nerve
X) lies dorsolat eral t o t he hypoglossal nucleus and sends f ibers t hat join t he
mot or root s of t he vagus and spinal accessory nerves. The nucl eus and tractus
sol i tari us (cranial nerves VI I , I X, and X) lie vent rolat eral t o t he dorsal mot or
nucleus of t he vagus, and t he medi al and spi nal vesti bul ar nucl ei and t he dorsal
and ventral cochl ear nucl ei (cranial nerve VI I I ) are locat ed at t he dorsal and
vent ral borders of t he i nf eri or cerebel l ar peduncl e ( resti f orm body). The i nf eri or
ol i vary nucl eus is locat ed w it hin t he olive.
The nucl eus graci l i s and nucl eus cuneatus are locat ed in t he post erior f uniculi of
t he dorsal medulla and give rise t o f ibers (i nternal arcuate f i bers) t hat cross in
t he decussat ion of t he lemniscus (great sensory decussat ion). These f ibers t hen
t ravel in t he medi al l emni scus, w hich is dorsomedial t o t he pyrami ds. The
nucl eus of the spi nal tract of the tri gemi nal nerve (pars caudal i s) lies lat eral t o
t he int ernal arcuat e f ibers and descends caudally t o t he level of C3 in t he
cervical spinal cord, w hereas t he spi nal tract of the tri gemi nal nerve lies lat eral
t o t he nucleus. The pyramids are locat ed in t he ant erior (vent ral) medulla and
cont ain descending cort icospinal t ract f ibers t o t he lat eral and ant erior
cort icospinal t ract s of t he spinal cord. The pyramid also cont ains descending
cort icobulbar f ibers. I n t he caudal end of t he medulla, nearly 75% t o 90% of t he
cort icospinal f ibers in t he pyramid cross t he vent ral midline (decussati on of the
pyrami ds or great mot or decussat ion) t o t he opposit e side t o f orm t he lat eral
cort icospinal t ract . The rest of t he cort icospinal t ract descends homolat erally t o
f orm t he ant erior cort icospinal t ract . There is a somat ot opic organizat ion of t he
cort icospinal f ibers w it hin t he pyramids, w it h t he f ibers of t he low er ext remit ies
placed more lat erally t han t he f ibers of t he upper ext remit ies[1] . The medi al
l ongi tudi nal f asci cul us is locat ed in t he dorsomedial medulla. O t her medullary
t ract s include t he vent ral and dorsal spinocerebellar t ract s, t he medial and
lat eral ret iculospinal t ract s, t he medial and lat eral vest ibulospinal t ract s, t he
rubrospinal t ract s, t he spinot halamic t ract s, and descending sympat het ic
pat hw ays.
FI G URE 15-1 The brainst em (vent ral view )

FI G URE 15-2 Midport ion of t he medulla at t he origin of t he hypoglossal and
vagus nerves. Myelin-st ained sect ion is show n at right . (From Daube JR,
Reagan TJ, Sandok BA, et al. Medi cal neurosci ences: an approach to
P. 351
Vascular Supply of the Medulla

The large regional art eries of t he brainst em have t he f ollow ing t hree t ypes of
branches:
1. The paramedi an arteri es, w hich penet rat e t he vent ral brainst em surf ace and
supply t he midline st ruct ures.
2. The short circumf erent ial art eries, w hich t raverse lat erally on t he brainst em
and penet rat e it s vent rolat eral and lat eral surf aces.
3. The long circumf erent ial art eries, w hich course around t he brainst em and
supply it s post erior st ruct ures and cerebellum.
The medulla oblongat a receives it s blood supply f rom t he ant erior and post erior
spinal art eries, t he post erior inf erior cerebellar art ery, and branches of t he
vert ebral art eries. The blood supply t o t he medulla may be subdivided int o t w o
groups: t he paramedian bulbar branches and t he lat eral bulbar branches.
Paramedian Bulbar Branches

The paramedian port ion of t he medulla (t he hypoglossal nucleus and emergent
nerve f ibers, t he medial longit udinal f asciculus, t he medial lemniscus, t he
pyramids, and t he medial part of t he inf erior olivary nucleus) are supplied by t he
vertebral artery. At low er medullary levels, t he anteri or spi nal artery also
cont ribut es t o t he paramedian zone.
FI G URE 15-3 Cross-sect ion of medulla oblongat a show ing area involved in
medial medullary inf arct ion and lat eral medullary inf arct ion (Wallenberg
syndrome). CN = cranial nerve
Lateral Bulbar Branches

The lat eral port ion of t he medulla is supplied by t he int racranial vertebral artery
(f ourth segment) or t he posteri or i nf eri or cerebel l ar artery. O ccasionally, t he
basilar art ery or t he ant erior inf erior cerebellar art ery also cont ribut es.
Medullary Syndromes
M edial M edullary Syndrome (Dejerine's Anterior Bulbar
Syndrome)
This syndrome of t en result s f rom at herosclerot ic occlusion of t he vert ebral
art ery, ant erior spinal art ery, or t he low er segment of t he basilar art ery.
Vert ebrobasilar dissect ion, dolichoect asia of t he vert ebrobasilar syst em,
embolism, and meningovascular syphilis are less common causes of t he medial
medullary inf arct ion[134] . The ant erior spinal art ery supplies t he paramedian
region of t he medulla oblongat a, w hich includes t he ipsilat eral pyramid, medial
lemniscus, and hypoglossal nerve and nucleus (Fig. 15-3). I t s occlusion t heref ore
result s in t he f ollow ing signs:
1. I psilat eral paresis, at rophy, and f ibrillat ion of t he t ongue (due t o cranial
nerve XI I aff ect ion). The prot ruded t ongue deviat es t ow ard t he lesion (aw ay
f rom t he hemiplegia). Cranial nerve XI I f unct ion may be spared[107] .
2. Cont ralat eral hemiplegia (due t o involvement of t he pyramid) w it h sparing of
t he f ace.
3. Cont ralat eral loss of posit ion and vibrat ory sensat ion (due t o involvement of
t he medial lemniscus). The more t he dorsolat eral spinot halamic t ract is
unaff ect ed, t he more t he pain and t emperat ure sensat ion are spared.
4. O ccasionally, upbeat nyst agmus may occur because of dorsal ext ension of
t he inf arct t ow ard t he medial longit udinal f asciculus[62] . I t has also been
proposed t hat a unilat eral lesion of t he nucleus int ercalat us can account f or
primary posit ion upbeat nyst agmus due t o a unilat eral medial medullary
inf arct ion[ 61] .
The medial medullary syndrome may occur bilat erally [81, 50] result ing in f laccid
quadriplegia (w it h f acial sparing), bilat eral low er mot or neuron lesions of t he
t ongue, complet e loss of posit ion and vibrat ory sensat ion aff ect ing all f our
ext remit ies and respirat ory f ailure, or acut e onset of t riparesis (w it h involvement
of bot h low er limbs and cont ralat eral upper ext remit y), suggest ive of a possible
f iber seggregat ion of t he descending t ract s of diff erent ext remit ies[51] .
Because t he hypoglossal f ibers run somew hat lat erally t o t he medial lemniscus
and pyramid, t hey are occasionally spared in cases of ant erior spinal art ery
occlusion. O ccasionally, only t he pyramid is damaged, result ing in a pure motor
hemi pl egi a t hat spares t he f ace [26, 108, 115] . Cent ral f acial paresis may also
result f rom a unilat eral cont ralat eral medullary inf arct ion, suggest ing t hat some
of t he f acial cort icobulbar f ibers descend ipsilat erally bef ore making a loop as
low as t he medulla oblongat a bef ore decussat ing and ascending t o t he
cont ralat eral f acial nucleus t hat innervat es t he perioral musculat ure [23, 127] . A
crossed motor hemi paresi s ( hemi pl egi a cruci ata), w it h paralysis of t he
ipsilat eral arm and t he cont ralat eral leg (result ing f rom a low er medullary lesion
compromising t he crossed f ibers t o t he arm as w ell as t he uncrossed f ibers t o
t he leg), is an ext remely rare occurrence[11] .
Apart f rom incomplet e syndromes (e. g. , medial medullary syndrome present ing
as pure mot or hemiparesis, or medial medullary syndrome w it hout t ongue
paralysis), ot her unusual neurologic f indings may be observed including
cont ralat eral paralysis of t he pharyngeal const rict or muscle[93] and cont ralat eral
t ongue paralysis[24] .
Lateral M edullary (Wallenberg) Syndrome

This syndrome [28, 29, 47, 69, 90, 95, 112] is most of t en secondary t o
int racranial vert ebral art ery or post erior inf erior cerebellar art ery occlusion.
Spont aneous dissect ions of t he vert ebral art eries are a common cause [67, 88] .
The syndrome has also been described w it h cocaine abuse[87] , medullary
neoplasms (usually met ast ases), abscess, demyelinat ing disease[120] ,
radionecrosis, hemat oma (secondary t o rupt ure of a vascular malf ormat ion),
neck manipulat ion[49] , t rauma, bullet injury t o t he vert ebral art ery[102] , and
post erior spinal f usion surgery w it h inst rument at ion in a pat ient w it h a previously
undiagnosed Chiari 1 malf ormat ion[109] . The charact erist ic clinical pict ure
result s f rom damage t o a w edge-shaped area of t he lat eral medulla (Fig. 15-3)
and inf erior cerebellum and consist s of several signs:
1. I psilat eral f acial hypalgesia and t hermoanest hesia (due t o t rigeminal spinal
nucleus and t ract involvement ). I psilat eral f acial pain is common[29] .
2. Cont ralat eral t runk and ext remit y hypalgesia and t hermoanest hesia (due t o
damage t o t he spinot halamic t ract ).
3. I psilat eral palat al, pharyngeal, and vocal cord paralysis w it h dysphagia and
dysart hria (due t o involvement of t he nucleus ambiguus).
4. I psilat eral Horner syndrome (due t o aff ect ion of t he descending sympat het ic
f ibers). I psilat eral hypohidrosis of t he body may occur, probably due t o
int errupt ion of t he most ly uncrossed excit at ory sw eat ing pat hw ay, w hich
descends f rom t he hypot halamus t hrough t he t egment al area of t he
mesencephalon and pons and, more caudally, t hrough t he post erolat eral area
of t he medulla t o synapse w it h t he sympat het ic sudomot or neurons of t he
int ermediolat eral cell column of t he spinal cord[72] .
5. Vert igo, nausea, and vomit ing (due t o involvement of t he vest ibular nuclei).
6. I psilat eral cerebellar signs and sympt oms (due t o involvement of t he inf erior
cerebellar peduncle and cerebellum).
7. O ccasionally, hiccups (singult us) at t ribut ed t o lesions of t he dorsolat eral
region of t he middle medulla[98] and diplopia (perhaps secondary t o
involvement of t he low er pons).
Lat eral lesions locat ed in t he rost ral medulla are associat ed w it h more severe
dysphagia, hoarseness, and t he presence of f acial paresis, w hereas more
caudal lesions sit uat ed in t he lat eral surf ace of t he medulla, correlat e w it h more
marked
vert igo, nyst agmus, and gait at axia[69] . Nausea, vomit ing, and Horner syndrome
are common regardless of t he locat ion of t he lesion in t he lat eral medulla;
lesions t hat ext end more vent romedially cause f acial sensory changes on t he
cont ralat eral side of t he lesion[69] . The mot or syst em (pyramids), t ongue
movement s, and vibrat ion and posit ion sense are t ypically spared w it h lat eral
medullary lesions because t he corresponding anat omic st ruct ures are locat ed in
t he medial medulla. The t riad of Horner syndrome, ipsilat eral at axia, and
cont ralat eral hypalgesia clinically ident if ies pat ient s w it h lat eral medullary
inf arct ion[ 112] . Cerebellar inf arct s only inf requent ly accompany t he lat eral
medullary syndrome, suggest ing t hat most of t he post erior inf erior cerebellar
art ery t errit ory is spared, despit e t he high f requency of vert ebral art ery
occlusion as a cause of t his syndrome[112] .
Headache, especially unilat eral headache localized t o t he upper post erior
cervical region, is common w it h t he lat eral medullary syndrome, part icularly
w hen t he syndrome is due t o cervical vert ebral art ery dissect ion [56, 88] . This
t ype of headache should be dist inguished f rom t he rare paroxysmal ret ro-orbit al
hemicranial-like at t acks report ed af t er st rokes involving t he dorsal medulla and
high cervical spinal cord at t he C1 level[32] .
The sensory def ect in t he lat eral medullary syndrome usually aff ect s t he
ipsilat eral f ace and t he cont ralat eral leg, arm, and t runk. How ever, several
pat ient s w it h lat eral brainst em lesions developed a sensory def ect involving t he
ipsilat eral f ace and t he cont ralat eral f oot , w it h t he lat t er def ect ext ending
upw ard t o end in a sensory level[79] . These pat ient s w it h a crossed pattern of
sensory def ect had f ar lat eral lesions of t he lat eral medulla and pons, w it h t he
leg and low er t orso involvement due t o select ive part ial disrupt ion of t he
somat ot opically organized sacral and lumbar aff erent f ibers of t he lat eral
spinot halamic t ract (locat ed f ar lat erally in t he brainst em), w it h sparing of t he
more medial t horacic and cervical f ibers[79] . Several pat ient s have also been
described w it h a cont inuous hemisensory def ect of t he f ace, arm, and t runk
(uni l ateral pattern), w it h t he low er border demarcat ed at a sensory level[79] .
These pat ient s w ere t hought t o have mediolat eral medullary and pont ine lesions
cont ralat eral t o t he side of t he sensory def ect , w hich aff ect ed t he medial
cervical and t horacic aff erent s of t he lat eral spinot halamic t ract (i. e. , spared t he
lat eral sacral and lumbar aff erent s) and t he vent ral t rigeminot halamic t ract
(account ing f or cont ralat eral f acial sensory loss), but spared t he spinal nucleus
and t ract of t he t rigeminal nerve.
Rare manif est at ions of t he Wallenberg syndrome include t he f ollow ing:
1. Wild arm at axia w hich is probably relat ed t o involvement of t he lat eral

cuneat e nucleus [30, 28] .
2. Clumsiness of t he ipsilat eral upper limb result ing f rom ext ension of t he injury
int o t he subolivary area[19] .
3. Cent ral pain w hich is associat ed w it h allodynia[101] .
4. Cont ralat eral hyperhydrosis w it h ipsilat eral anhidrosis due t o int errupt ion of
t he sympat het ic pat hw ays (not ed a f ew mont hs af t er inf arct ion)[ 110] .
5. An inabilit y t o sneeze due t o compromise of t he sneezing cent er locat ed at
t he vent romedial margin of t he descending t ract and nucleus (spinal nucleus)
of t he t rigeminal nerve[60] .
6. Loss of t ast e w hich result s f rom involvement of t he rost ral and t he lat eral
zone of t he nucleus t ract us solit arius[52] .
7. Aut onomic dysf unct ion including t achycardia, blood pressure labilit y, and
respirat ory f ailure f rom t he involvement of t he caudal and medial zone of t he
nucleus t ract us solit arius[21] .
8. Failure of aut omat ic breat hing (O ndine's curse) due t o discret e lesions of t he
nucleus ambiguus and t he adjacent ret icular f ormat ion.
9. Body lat eropulsion w it hout limb at axia f rom t he involvement of t he
descending lat eral vest ibulospinal t ract , or body lat eropulsion w it h limb
at axia due t o int errupt ion of t he ascending dorsal spinocerebellar t ract [130] .
10. Axial lat eral pulsion w hich result s f rom t he involvement of t he vest ibulospinal
and spinocerebellar t ract s as w ell as cent ral vest ibular pat hw ays[5] .
11. Pure sensory st roke w it h loss of pain and t emperat ure involving t he f ace,
arm, t runk, and leg as t he only manif est at ions of t he lat eral medullary
inf arct ion [6, 12] .
12. I psilat eral hemiparesis f rom t he involvement of t he low er most caudal end of
t he medulla just below t he pyramidal decussat ion[33] . An ipsilat eral spast ic
hemiplegia associat ed w it h a lat eral medullary syndrome is also know n as
the submedul l ary syndrome of O pal ski (see subsequent t ext )[ 89] .
13. Cent ral hypovent ilat ion is seen along w it h vasomot or inst abilit y[74] .
14. Post st roke f acial pain w hich result s f rom t he involvement of t he primary
aff erent f ibers in t he descending spinal t rigeminal t ract [46] .
Various abnormalit ies of eye movement s and vision have been described w it h t he
lat eral
medullary syndrome (Table 15-1)[ 15, 18, 34, 83] . These include t he f ollow ing:
1. Dysf uncti on of ocul ar al i gnment. Lat eral medullary lesions damage t he

ot olit hic vest ibular nuclei and, t heref ore, pat ient s w it h Wallenberg syndrome
of t en demonst rat e skew devi ati on w it h hypot ropia on t he side of t he lesion
[ 68] . Brandt and Diet erich have called t his type 2 skew devi ati on and st at ed
t hat t his skew result s f rom elevat ion of t he cont ralat eral eye, w it hout vert ical
displacement of t he ipsilat eral eye [16, 17] . Some pat ient s also show an
ipsilat eral head ti l t and a disconjugat e ocul ar torsi on (t he ocular t ilt react ion,
see Chapt er 8) w it h excyclodeviat ion of t he ipsilat eral low er eye but w it h
lit t le or no incyclodeviat ion of t he cont ralat eral higher eye [17, 34, 90] .
Theref ore, pat ient s may complain of diplopia w it h images displaced vert ically
and t ilt ed w it h respect t o each ot her. Some pat ient s w it h Wallenberg
syndrome may also exhibit ocular ipsipulsion due t o damage t o t he climbing
f ibers f rom t he cont ralat eral inf erior olivary nucleus t o t he dorsal vermis[70]
or complain of t he unusual (and almost unbelievable) sensat ion of
envi ronmental ti l t, in w hich t he w hole room is t ilt ed on it s side or even
upside dow n (“f loor-on-ceiling” phenomenon) [34, 107] . This syndrome is
also probably caused by a dist urbance of vest ibular-ot olit h cent ral
connect ions[ 107] . Environment al t ilt or “upside dow n” reversal of vision may
also occur w it h vert ebrobasilar t ransient ischemic at t acks[122] ,
vert ebrobasilar ischemia[123] , encephalit is, head injury[83] , demyelinat ing
disease[ 117] , or af t er t hird vent riculost omy f or hydrocephalus[97] .
Damage t o ot olit hic cent ral project ions mediat ing ocular count er-roll may
also cont ribut e t o t he genesis of torsi onal nystagmus (see subsequent t ext )
in t he lat eral medullary syndrome[90] . Cent ral ot olit hic involvement may also
be responsible f or t he see-saw nyst agmus observed in occasional pat ient s
[ 55, 86] . See-saw nyst agmus is a disjunct ive, vert ical-t orsional nyst agmus
half cycle, w hich consist s of elevat ion and int orsion of one eye w it h
synchronous depression and ext orsion of t he ot her eye; t he next half cycle
consist s of t he reversal of t hese vert ical and t orsional movement s. This t ype
of nyst agmus is usually pendular and not ed especially w it h large, ext ensive
suprasellar lesions t hat compress or inf ilt rat e t he mesodiencephalon
bilat erally. Wit h lat eral medullary lesions, how ever, a jerk see-saw
nyst agmus may occur [55, 90] . The t orsional component of t his nyst agmus is
conjugat e w it h t he f ast component cont raversive t o t he side of t he lesion[55] .
This cont rast s w it h t he jerk see-saw nyst agmus described w it h unilat eral,
f ocal mesodiencephalic lesions, in w hich t he quick phase of t he t orsional
component is t ow ard t he side of t he lesion[55] .
2. Nystagmus. Nyst agmus in t he lat eral medullary syndrome may be due t o
direct damage t o t he vest ibular nuclei or t heir cerebellar, semicircular canal,
or ot olit hic connect ions. Nyst agmus in t he lat eral medullary syndrome is
usually posit ional and can be horizont al[36] , t orsional[90] , or mixed, w it h
t orsion, vert ical, and horizont al component s[8] . Typically, horizont al
nyst agmus beat s aw ay f rom t he side of t he lesion, w it h t he horizont al drif t
velocit y direct ed t ow ard t he side of t he lesion being inf luenced by eye
posit ion and by f ixat ion. O ccasionally, t he nyst agmus may beat w it h t he f ast
component ipsilat erally during gaze t ow ard t he side of t he lesion or during
eye closure[8] . A vert ical nyst agmus is usually upbeat ing[8] . The nyst agmus
is of t en evident only in t he init ial days af t er dorsolat eral
medullary inf arct ion, and rapidly declines over t he f ollow ing days[105] .
Torsional nyst agmus is common w it h Wallenberg syndrome, w it h t he upper
pole of t he iris beat ing aw ay f rom t he side of inf arct ion[90] . Torsional
nyst agmus has been at t ribut ed t o an imbalance of cent ral project ions f rom
t he ant erior and post erior semicircular canals and t he ot olit hic recept ors t hat
mediat e ocular count er-roll[ 90] .
As ment ioned in t he preceding t ext , see-saw nyst agmus may also occur w it h
lat eral medullary lesions[86] . G aze-evoked eyelid nyst agmus associat ed w it h
ocular nyst agmus has been described, in w hich a clinically obvious upw ard
jerking of t he lids occurred synchronously w it h t he f ast phase of a gaze-
evoked horizont al nyst agmus[31] . This eyelid nyst agmus w as inhibit ed or
t ot ally arrest ed by t he near ref lex.
3. Smooth pursui t and gaze-hol di ng abnormal i ti es. St ruct ures and pat hw ays
locat ed in t he lat eral medulla are also concerned w it h smoot h pursuit eye
movement s and gaze holding[140] . The cerebellar f locculus, paraf locculus,
and vermis climbing f ibers pass t hrough t he inf erior cerebellar peduncle and
are concerned w it h t hese f unct ions.
Pat ient s w it h t he lat eral medullary syndrome may complain of a sensat ion of
t heir bodies being pulled t o one side and at t empt t o count eract t his
lat eropulsion of t he body by leaning t ow ard t he opposit e side. Because of
gaze-holding impairment , ocular movement s may be similarly aff ect ed, w it h a
t endency f or t he eyes t o be “pulled” t ow ard t he involved medulla
(l ateropul si on or i psi pul si on of eye movements) [8, 36, 48, 82, 136, 139] . I f
a pat ient is asked t o f ixat e st raight ahead and close t he eyelids, t he eyes
w ill deviat e t ow ard t he side of t he medullary lesion (ref lect ed by a series of
small correct ive hypomet ric saccadic [ f ast ] eye movement s in t he opposit e
direct ion, w hich are direct ed t o f ixat ion w hen t he eyes are again opened).
Even blinking may induce t his lat eropulsion. These abnormalit ies of gaze
holding may also be ref lect ed in saccadic eye movement abnormalit ies.
Smoot h pursuit eye movement s t racking t arget s moving aw ay f rom t he side
of t he lesion are also impaired w it h lat eral medullary lesions, w hereas
pursuit t ow ard t he side of t he lesion is normal, or nearly so [8, 82, 140] .
4. Abnormal i ti es of saccades. The cerebellum may be involved in modulat ing
t he amplit ude but not t he speed of saccadic (f ast ) eye movement s.
I nt errupt ion of cerebellar cent ral connect ions t hat t raverse t he lat eral
medulla probably account s f or some of t he observed ocular mot or def icit s
[ 112] . Damage t o t he juxt arest if orm body, w hich carries signals f rom t he
f ast igial nucleus t o t he brainst em ret icular f ormat ion, may account f or a
saccadic abnormalit y ref erred t o as l ateropul si on of saccadi c eye
movements[ 75] .
TABLE 15-1 Ocular M otor Abnormalities in Wallenberg

Lateral M edullary Syndrome
Dysfunction of ocular alignment

Skew deviation
Ocular tilt reaction
Environmental tilt/“floor-on-ceiling” phenomenon
See-saw nystagmus
Nystagmus (multiple pathways or pathways involved)
Horizontal
Torsional
Mixed horizontal-torsional
Mixed horizontal-torsional-vertical
See-saw nystagmus
Eyelid nystagmus
Smooth pursuit and gaze-holding abnormalities
Ipsilateral eye deviation
Impaired contralateral smooth pursuit
Lateropulsion of pursuit
Abnormalities of saccades
Ipsipulsion (lateropulsion)
Torsipulsion
Oblique saccade trajectories on vertical gaze
attempts
As not ed in t he preceding t ext , gaze-holding abnormalit ies in pat ient s w it h

Wallenberg syndrome may result in ipsipulsion of eye movement s. This disorder
of gaze holding may also induce saccadic abnormalit ies. Horizont al saccades
aw ay f rom t he side of t he lesion are hypomet ric (undershoot t he t arget ),
w hereas saccades direct ed t ow ard t he side of t he lesion are hypermet ric
(overshoot t he t arget )[ 139] . Q uick phases of nyst agmus are similarly aff ect ed.
I psipulsion w it h lat eral medullary lesions is t heref ore opposit e t o t he
cont rapulsion of saccades t hat occurs w it h lesions of t he superior cerebellar
peduncle [106, 136] .
Pat ient s w it h Wallenberg syndrome may have permanent saccadic dysmet ria
(hypermet ria t o t he side of t he lesion and hypomet ria t o t arget s cont ralat eral t o
t he lesion) and a reduced capabilit y t o readjust saccadic amplit ude[139] . This
horizont al saccade bias w it h lat eral medullary lesions is also ref lect ed in vert ical
eye movement s. O n at t empt ing t o make a purely vert ical saccade, an oblique or
ellipt ical saccade direct ed t ow ard t he lesion (in t he direct ion of lat eropulsion) is
made, requiring correct ive saccades aw ay f rom t he side of t he lesion t o bring
t he eyes back t ow ard t he int ended t arget . Lat er, at t empt ed vert ical saccades
may t ake on S-shaped t raject ories as an adapt ive st rat egy t o correct t he
saccadic dysmet ria[75] . Even a t orsional component of t his bias may occur
(t orsipulsion), w it h inappropriat e t orsional f ast eye movement s induced during
saccades t ow ard or aw ay f rom t he side of t he medullary lesion[90] .
The medi al branch of the posteri or i nf eri or cerebel l ar artery supplies t he
dorsolat eral medulla; inf arct s of t his branch may be clinically silent , cause
isolat ed vert igo of t en misdiagnosed as labyrint hit is, cause vert igo associat ed
w it h ipsilat eral lat eropulsion of t he t runk and gaze and dysmet ria or
unst eadiness, or cause a f ull Wallenberg syndrome [3, 4, 54, 65] . Bi l ateral
cerebellar inf arct ion in t he t errit ory of t he medial branches of t he post erior
inf erior cerebellar art eries may cause vert igo, dysart hria, dysequilibrium w it h
ret ropulsion, bilat eral gaze-evoked nyst agmus, and marked gait at axia w it hout
brainst em signs[124] . Vert igo and upside-dow n vision have been described
because of an inf arct in t he cerebellar f locculus and
nodulus due t o aff ect ion of t he medial branch of t he post erior inf erior cerebellar
art ery[ 25] .
At herosclerot ic occlusion or dissect ion of t he int racranial vert ebral art ery can
lead t o a t ot al unilat eral hemi medul l ary ( Babi nski -Nageotte) syndrome, a
combinat ion of t he medial and lat eral medullary syndromes[91] . This rare
syndrome is charact erized by cont ralat eral hemiplegia and sensory loss of t he
limbs and t runk, ipsilat eral hemiat axia, and f acial sensory loss, along w it h
dysphagia, dysphonia, and dysart hria. I psilat eral hemiparesis is ext remely
rare[ 77] . Some aut horit ies have suggest ed Reinhold's syndrome as t he proper
eponym f or t he hemimedullary syndrome[73] . Because of t he separat e art erial
t opography supplying t he medulla, t he simult aneous occurrence of ischemic
lesions involving t he lat eral and medial part s of t he medulla is ext remely
rare[ 91] . Combinat ions of t he t w o major syndromes may also occur as bilat eral
medial and bilat eral lat eral medullary syndromes[52] .
Tegment al medullary lesions (e. g. , glioma) may cause lack of appet it e and early
sat iet y (medullary sat iet y), implying t hat t he medulla may play a role in t he
regulat ion of f eeding behaviors[78] . Lesions aff ect ing t he obex of t he medulla
may result in neurogenic pulmonary edema[119] . This support s t he hypot hesis
t hat lesions of caudal brainst em st ruct ures, especially t he nucleus t ract us
solit arius, t he dorsal mot or nucleus of t he vagus, and t he medial ret icular
f ormat ion are responsible f or t he generat ion of neurogenic pulmonary edema.
Lesions of t he area postrema, an emet ic cent er locat ed in t he caudal part of t he
f ourt h vent ricle and lacking a blood–brain barrier, lesions of t he dorsolat eral
pont ine t egment um, as w ell as ot her lesions of t he low er brainst em, may account
f or vomit ing, of t en out of proport ion t o dizziness[43] .
Opalski (Submedullary) Syndrome)

When ipsilat eral hemiplegia is associat ed w it h sympt oms of a lat eral medullary
syndrome, it corresponds t o t he submedul l ary syndrome of O pal ski. O palski
syndrome result s f rom an occlusion of t he vert ebral art ery. The ipsilat eral
hemiplegia is due t o a lesion of t he low er medulla involving t he cort icospinal t ract
af t er t he pyramidal decussat ion [63, 96] .
Lateral Pontomedullary Syndrome

This syndrome[41] may result f rom occlusion of an aberrant art erial branch
arising f rom t he upper vert ebral art ery and running superiorly and lat erally t o t he
region of exit of cranial nerves VI I and VI I I f rom t he pons. I t may also occur w it h
pont ine hemorrhage[2] . The clinical f indings are t hose seen in t he lat eral
medullary syndrome plus several pont ine f indings, w hich includes t he f ollow ing:
1. I psilat eral f acial w eakness (due t o involvement of cranial nerve VI I )

2. I psilat eral t innit us and, occasionally, hearing dist urbance (due t o involvement
of cranial nerve VI I I )
The Pons
Anatomy of the Pons
The pons (Fig. 15-1)[ 20] is part of t he met encephalon (pons and cerebellum),
and ext ends f rom a caudal plane, w hich passes f rom t he st riae medullaris
post eriorly t hrough t he pont omedullary sulcus ant eriorly, t o a cephalad plane,
w hich passes immediat ely caudal t o t he inf erior colliculi (dorsally) and t o t he
cerebral peduncles (vent rally). The dorsal part of t he pons is ref erred t o as t he
tegmentum, and t he vent ral port ion is ref erred t o as t he basi s ponti s, basi l ar
pons, or pontocerebel l ar port ion (Fig. 15-4). The pont ine t egment um is
composed largely of t he pont ine ret icular f ormat ion, w hich is a rost ral
cont inuat ion of t he medullary ret icular f ormat ion. This cent ral core is generally
divided int o a medial region of primarily large neurons (magnocellular region) and
a lat eral region of mainly small neurons (parvocellular region). The basis pont is
cont ains t he pont ine nuclei and mult idirect ional nerve f iber bundles.
Crani al nerve nucl ei in t he pons include t he nucleus of t he abducens nerve
(cranial nerve VI ), w hich is locat ed in t he dorsomedial pons just beneat h t he
f loor of t he f ourt h vent ricle. Fibers f rom t his nucleus pass vent rally bet w een
bundles of cort icospinal t ract f ibers t o exit at t he pont omedullary junct ion.
Vent romedial t o t he abducens nucleus is t he paramedi an ponti ne reti cul ar
f ormati on Paramedi an Ponti ne Reti cul ar Formati on ( PPRF), w hich plays an
import ant role in t he cont rol of saccadic eye movement s (see Chapt er 8). The
motor nucl eus of the f aci al nerve (cranial nerve VI I ) is sit uat ed vent rolat erally.
Fibers f rom t his nucleus run dorsomedially t ow ard t he f loor of t he f ourt h
vent ricle, make an acut e bend around t he abducens nucleus, and t hen t urn
lat erally t hrough t he pons t o exit lat eral t o t he abducens nerve f ibers. The mai n
motor and mai n sensory nucl ei of the tri gemi nal nerve (cranial nerve V) are
locat ed dorsolat erally, as are t he cochl ear nucl ei and t he l ateral and superi or
vesti bul ar nucl ei (cranial nerve VI I I ). The superi or and i nf eri or sal i vatory nucl ei
and t he l acri mal nucl eus (cranial nerves VI I and I X) are also locat ed in t he pons.
FI G URE 15-4 Cross-sect ion of t he low er pons at t he level of cranial nerves

VI and VI I . Myelin-st ained sect ion is show n on t he right . (From Daube JR,
Fi ber tracts wi thi n the pons include t he medi al l ongi tudi nal f asci cul us, w hich is
sit uat ed dorsomedially, and t he medi al l emni scus, w hich lies dorsal t o t he
corti cospi nal , corti cobul bar, and corti coponti ne f iber bundles. O t her t ract s w it hin
t he pons include t he vent ral spinocerebellar, spinot halamic, lat eral t ect ospinal,
rubrospinal, and cort icopont ocerebellar t ract s. The pons also cont ains audi tory
connecti ons, including t he lat eral lemniscus, t he nucleus of t he lat eral lemniscus,
t he t rapezoid body, and t he superior olivary nuclear complex. The brachi um
ponti s or mi ddl e cerebel l ar peduncl e connect s t he vent ral pons w it h t he
cerebellum.
Vascular Supply of the Pons

At t he low er border of t he pons, t he paired vert ebral art eries f use in t he midline
t o f orm t he basilar art ery. The f irst branch of t he basilar art ery is t he ant erior
inf erior cerebellar art ery. Then comes a series of paramedian and short
circumf erent ial pont ine branches, and penult imat ely, t he superior cerebellar
art ery. Finally, t he basilar art ery divides int o t he t w o post erior cerebral art eries.
The blood supply t o t he pons may be divided int o t hree groups.
Paramedian Vessels
The paramedian vessels (f our t o six in number) arise f rom t he basilar art ery and
penet rat e perpendicularly int o t he pont ine parenchyma. They supply t he medial
basal pons, including t he pont ine nuclei, t he cort icospinal f ibers, and t he medial
lemniscus.
Short Circumferential Arteries

The short circumf erent ial art eries also arise f rom t he basilar art ery and ent er t he
brachium pont is. These vessels supply t he vent rolat eral basis pont is.
Long Circumferential Arteries

The long circumf erent ial art eries supply most of t he pont ine t egment um and part
of t he middle cerebellar peduncles and include t he f ollow ing:
1. The superi or cerebel l ar artery, w hich arises f rom t he basilar art ery near it s
bif urcat ion, supplies t he dorsolat eral pons and brachium pont is, t he dorsal
ret icular f ormat ion, and t he periaqueduct al region (occasionally, t he
vent rolat eral pont ine t egment um is also supplied by t his vessel).
2. The anteri or i nf eri or cerebel l ar artery, w hich most of t en arises f rom t he
basilar art ery and supplies t he lat eral t egment um of t he low er t w o-t hirds of
t he pons and t he vent rolat eral cerebellum.
3. The i nternal audi tory artery, w hich arises f rom t he ant erior inf erior
cerebellar art ery (occasionally f rom t he basilar art ery) and supplies t he
audit ory, vest ibular, and f acial cranial nerves.
Pontine Syndromes
Numerous classical brainst em (eponymous) syndromes f eat uring cranial nerve
palsies, cerebellar signs, long t ract signs, and sensory dist urbances w ere
inst rument al in est ablishing t he seminal guidelines f or brainst em
localizat ion[ 118] .
Ventral Pontine Syndromes

Millard-Gubler Syndrome
A unilat eral lesion of t he vent rocaudal pons may involve t he basis pont is and t he
f ascicles of cranial nerves VI and VI I . This involvement result s in t he f ollow ing:
1. Cont ralat eral hemiplegia (sparing t he f ace) is due t o pyramidal t ract

involvement .
2. I psilat eral lat eral rect us paresis (cranial nerve VI ) w it h diplopia t hat is
accent uat ed w hen t he pat ient “looks t ow ard” t he lesion.
3. I psilat eral peripheral f acial paresis (cranial nerve VI I ).
Raymond Syndrome
A unilat eral lesion of t he vent ral medial pons, w hich aff ect s t he ipsilat eral
abducens nerve f ascicles and t he cort icospinal t ract but spares cranial nerve VI I ,
may cause t his rare syndrome (also called al ternati ng abducens hemi pl egi a)
[ 114] , w hich consist s of t he f ollow ing:
1. I psilat eral lat eral rect us paresis (cranial nerve VI )

2. Cont ralat eral hemiplegia, sparing t he f ace, due t o pyramidal t ract
involvement x
Pure Motor Hemiparesis

Lesions (especially lacunar inf arct ion) involving t he cort icospinal t ract s in t he
basis pont is may produce a pure mot or hemiplegia w it h or w it hout f acial
involvement [41, 45, 84, 94] . Pat ient s of t en have severe dysart hria and
dysphagia. Bout s of uncont rollable laught er may also occur[116] ). O t her
locat ions of lesions causing pure mot or hemiplegia include t he post erior limb of
t he int ernal capsule, t he cerebral peduncle, and t he medullary pyramid[26] . A
combinat ion of dysart hria and a hist ory of previous t ransient gait abnormalit y or
vert igo f avor a pont ine lesion as t he cause of pure mot or hemiparesis rat her t han
a more common capsular lesion[94] .
Dysarthria–Clumsy Hand Syndrome

Vascular lesions in t he basis pont is (especially lacunar inf arct ion) [39, 41, 48,
53, 84] at t he junct ion of t he upper one-t hird and low er t w o-t hirds of t he pons
may result in dysart hria–clumsy hand syndrome. I n t his syndrome f acial
w eakness and severe dysart hria and dysphagia occur along w it h clumsiness,
impaired f inger dext erit y, and paresis of t he hand. Hyperref lexia and a Babinski's
sign may occur on t he same side as t he arm paresis, but sensat ion is spared. A
similar clinical present at ion may occur w it h lesions in t he genu of t he int ernal
capsule or w it h small, deep cerebellar hemorrhages[111] .
Ataxic Hemiparesis
A lesion (usually a lacunar inf arct ion) [40, 41, 44, 84] in t he basis pont is at t he
junct ion of t he upper one-t hird and t he low er t w o-t hirds of t he pons may result in
t he at axic hemiparesis (homolat eral at axia and crural paresis) syndrome. I n t his
syndrome hemiparesis t hat is more severe in t he low er ext remit y, is associat ed
w it h ipsilat eral hemiat axia and occasionally dysart hria, nyst agmus, and
parest hesias. The hemiparesis is also associat ed w it h hyperref lexia and a
Babinski's sign. The lesion is locat ed in t he cont ralat eral pons. The at axia is
unilat eral, probably because t ransverse f ibers originat ing f rom t he cont ralat eral
pont ine nuclei (and project ing t o t he cont ralat eral cerebellum) are spared[92] .
This syndrome has also been described w it h cont ralat eral t halamocapsular
lesions, lesions of t he cont ralat eral post erior limb of t he int ernal capsule, lesions
of t he cont ralat eral red nucleus, and w it h superf icial ant erior cerebral art ery
t errit ory inf arct s in t he paracent ral area [14, 59] .
As a rare occurrence, f ocal inf arct s in t he basilar pons have been associat ed
w it h dysart hria-dysmet ria, dysart hria-f acial paresis, or ipsilat eral gaze paresis
and int ernuclear opht halmoplegia [116] .
Locked-in Syndrome
Bilat eral vent ral pont ine lesions (inf arct ion, t umor, hemorrhage, t rauma, cervical
manipulat ion, t umor, pont ine abscess, encephalit is, art erit is, neuro-Behcet 's,
mult iple sclerosis, air embolism, heroin abuse, diazepam t oxicit y, or cent ral
pont ine myelinolysis) may result in t he locked-in syndrome (de-eff erent ed st at e)
[ 58, 99, 103] . This syndrome consist s of t he f ollow ing signs:
1. Q uadriplegia due t o bilat eral cort icospinal t ract involvement in t he basis

pont is
2. Aphonia due t o involvement of t he cort icobulbar f ibers innervat ing t he low er
cranial nerve nuclei
3. O ccasional impairment of horizont al eye movement s due t o bilat eral
involvement of t he f ascicles of cranial nerve VI
Because t he ret icular f ormat ion is not injured, t he pat ient is f ully aw ake. The
supranuclear ocular mot or pat hw ays lie dorsally and are t heref ore spared;
t heref ore, vert ical eye movement s and blinking are int act (t he pat ient may
act ually convey his w ishes in Morse code). I n t hrombosis of t he basilar art ery,
not inf requent ly a hemiparesis is present at an early st age (“herald hemiparesis”
of basilar art ery occlusion), w hen brainst em signs may be absent or f ew [42] .
Theref ore, a cerebral hemisphere localizat ion is suggest ed, but in a f ew hours
bilat eral hemiplegia appears, associat ed
w it h a locked-in syndrome or coma[42] . De-eff erent at ion may also occur w it h

purely peripheral lesions (e. g. , polio, polyneurit is, myast henia gravis).
Dorsal Pontine Syndromes

Foville Syndrome
This syndrome is due t o lesions involving t he dorsal pont ine t egment um in t he
caudal t hird of t he pons. I t consist s of t he f ollow ing:
1. Cont ralat eral hemiplegia (w it h f acial sparing) w hich is due t o int errupt ion of
t he cort icospinal t ract .
2. I psilat eral peripheral-t ype f acial palsy w hich is due t o involvement of t he
nucleus and f ascicle (or bot h) of cranial nerve VI I .
3. I nabilit y t o move t he eyes conjugat ely t o t he ipsilat eral side (gaze is “aw ay
f rom” t he lesion) due t o involvement of t he PPRF or abducens nucleus, or
bot h.
Raymond-Cestan Syndrome
The Raymond-Cest an syndrome is seen w it h rost ral lesions of t he dorsal pons. I t
includes t he f ollow ing:
1. Cerebellar signs (at axia) w it h a coarse “rubral” t remor w hich is due t o t he

involvement of t he cerebellum.
2. Cont ralat eral hypest hesia w it h reduct ion of all sensory modalit ies (f ace and
ext remit ies) w hich is due t o t he involvement of t he medial lemniscus and t he
spinot halamic t ract .
3. Wit h vent ral ext ension, t here may be cont ralat eral hemiparesis (due t o
cort icospinal t ract involvement ) or paralysis of conjugat e gaze t ow ard t he
side of t he lesion (due t o involvement of t he PPRF).
Paramedian Pontine Syndromes

Several clinical syndromes of paramedian pont ine inf arct ion have been
described. [ 9] .
1. Uni l ateral medi obasal i nf arcts. These pat ient s present w it h severe f acio-
brachio-crural hemiparesis, dysart hria, and homolat eral or bilat eral at axia.
2. Uni l ateral medi obasal i nf arcts. Most pat ient s show slight hemiparesis w it h
at axia and dysart hria, at axic hemiparesis, or dysart hria–clumsy hand
syndrome.
3. Uni l ateral medi obasal i nf arcts. Present at ions include dysart hria–clumsy
hand syndrome, at axic hemiparesis w it h prominent sensory or eye movement
disorders, and hemiparesis w it h cont ralat eral f acial or abducens palsy.
4. Uni l ateral medi obasal i nf arcts. These pat ient s have pseudobulbar palsy and
bilat eral sensorimot or dist urbances.
The most common et iology f or paramedian pont ine inf arct s is small vessel
disease; vert ebrobasilar large vessel disease and cardiac embolism are less
common causes[9] .
An unusual f inding observed in pat ient s w it h unilat eral paramedian pont ine
inf arct ion consist s of bilat eral Wallerian degenerat ion of t he middle cerebellar
peduncles[ 135] .
Lateral Pontine Syndromes

Marie-Foix Syndrome
This syndrome is seen w it h lat eral pont ine lesions, especially t hose aff ect ing t he
brachium pont is. I t consist s of t he f ollow ing:
1. I psilat eral cerebellar at axia due t o involvement of cerebellar connect ions

2. Cont ralat eral hemiparesis due t o involvement of t he cort icospinal t ract
3. Variable cont ralat eral hemihypest hesia f or pain and t emperat ure due t o
involvement of t he spinot halamic t ract
As a rare occurrence, pont ine lesions have been associat ed w it h anosognosia f or

t he hemiplegia[37] , blepharospasm[7] , brief clonic jerking and ot her convulsive-
like movement s[113] , jaw -opening dyst onia, [35] hemidyst onia[125] , a f ocally
enhanced st art led response[141] , sympt omat ic ort host at ic t remor[10] , t runcal
at axia w it hout limb at axia[85] , bilat eral deaf ness[133] , cheiro-pedal syndrome
w it h numbness of hand and f oot associat ed w it h hypest hesia and hypalgesia[66] ,
painf ul Horner syndrome[27] , int raoral sensory loss[38] , t rigeminal
neuralgia[ 100] , isolat ed cranial nerve palsies[128] , dist urbances of cognit ion and
aff ect , pat hologic crying, inappropriat e laught er (f ou ri re prodromi que) [116,
126] , and rapid eye movement sleep behavior[71] . I n ot her circumst ances, t hey
have mimicked an acut e peripheral vest ibulopat hy[129] . While lesions in t he
dorsolat eral pont ine t egment um may cause vomit ing, medial t egment al upper
pont ine lesions, probably aff ect ing t he PPRF bilat erally, may cause cent ral ref lex
hyperpnea, f ormerly called central neurogeni c hyperventi l ati on. Volit ional cent ral
f acial paresis result s f rom lesions involving t he cont ralat eral cort icobulbar f ibers.
Emot ional innervat ion of t he muscles of f acial expression is involunt ary and of
uncert ain origin. Volit ional t ype of f acial paresis w it h unimpaired emot ional
movement s t o emot ional st imuli has also been described indicat ing t hat t he
pat hw ays
subserving volit ional and emot ional input t o t he f acial nucleus are st ill
anat omically separat ed in t he upper pons [132, 137] . Conversely, emot ional
(mimet ic) f acial paresis has been not ed w it h dorsolat eral pont ine lesions
involving st ruct ures dist inct f rom t he cort icobulbar f ibers t hat mediat e volit ional
f acial innervat ion[64] .
The Syndrome of Universal Dissociative Anesthesia
Universal dissociat ive anest hesia is a rare syndrome t hat has been described in
a pat ient aff ect ed by combined right superior cerebellar art ery occlusion,
result ing in lat eral superior pont ine inf arct ion, and lef t post erior inf erior
cerebellar art ery occlusion, result ing in a lef t Wallenberg lat eral medullary
syndrome[ 138] . The pat ient had loss of pain and t emperat ure sensat ion over t he
f ace, neck, t runk, and all ext remit ies, w hereas light t ouch, vibrat ion, posit ion,
and deep pain sensat ion w ere preserved (dissociat ed sensory loss). This
int erest ing lesson in localizat ion w as due t o bilat eral discret e int errupt ion of
spinot halamic f ibers and t he spinal nucleus and t ract of t he t rigeminal nerve.
FI G URE 15-5 Cross-sect ion of t he mesencephalon. A: Low er mesencephalon

at t he level of inf erior colliculus. B: Upper midbrain at t he level of superior
colliculus. Myelin-st ained sect ions are show n below. (From Daube JR,
The clinical f indings w it h pont ine hemorrhage are discussed in Chapt er 21.
The M esencephalon
Anatomy of the Mesencephalon
The rost ral boundary of t he mesencephalon is t he superior colliculi—mammillary
bodies' plane; t he caudal boundary is t he plane just caudal t o t he inf erior colliculi
(Fig. 15-1). The midbrain (Fig. 15-5) may be divided int o t he dorsal tectumor
quadri gemi nal pl ate (cont aining t he colliculi), t he cent ral tegmentum, and t he
vent rally locat ed cerebral peduncl es[ 1] .
The dorsal tectum cont ains t he corpora quadrigemina, made up of f our rounded
eminences
arranged in pairs: t he superi or and i nf eri or col l i cul i. The t egment um cont ains
ascending and descending t ract s, ret icular nuclei, and w ell-delineat ed nuclear
masses. The cerebral peduncl es are vent ral and cont ain cort icopont ine f ibers
(f ront opont ine project ion) in t heir medial f if t h, cort icospinal t ract f ibers in t heir
middle t hree-f if t hs, and t emporopont ine f ibers in t heir lat eral f if t h. Fibers in t he
cort icospinal t ract are somat ot opically arranged w it h t he f ibers dest ined t o t he
arm medially placed and t hose t o t he leg lat erally locat ed, w it h t he t runk f ibers
in bet w een. The substanti a ni gra is a pigment ed layer possessing melanin
granules, dorsal t o t he peduncles and vent ral t o t he red nucl eus, composed of a
dorsal zona compacta and a ventral zona reti cul ata.
The nucleus of t he t rochlear nerve (cranial nerve I V) is locat ed in t he vent ral part
of t he cent ral gray mat t er at t he level of t he inf erior colliculus; t he nucl eus of
the ocul omotor nerve (cranial nerve I I I ) lies rost ral t o t he t rochlear nucleus
beneat h t he superior colliculus, just post erior t o t he medial longit udinal
f asciculus. Mesencephal i c tracts include t he crus cerebri, t he
dent at orubrot halamic t ract , t he medial t egment al t ract , t he medial longit udinal
f asciculus, t he post erior commissure, t he spinot halamic t ract , and t he medial
lemniscus.
Vascular Supply of the Mesencephalon

The mesencephalon receives it s blood supply f rom branches of t he basilar,
post erior cerebral, superior cerebellar, post erior communicat ing, ant erior and
post erior choroidal art eries.
The mesencephalon's vascular supply includes t he paramedian and t he
circumf erent ial vessels.
Paramedian Vessels
The paramedi an vessel s (t he ret romamillary t runk) arise f rom t he origins of t he
post erior cerebral art eries and include t he t halamoperf orat ing art eries (supplying
t he t halamus) and t he peduncular art eries (supplying t he medial peduncles and
t he midbrain t egment um, including t he oculomot or nucleus, t he red nucleus, and
t he subst ant ia nigra).
Circumferential Arteries
The ci rcumf erenti al (peripeduncular) arteri es include t he f ollow ing:
1. The quadri gemi nal arteri es (arising f rom t he post erior cerebral art eries),
w hich supply t he superior and inf erior colliculi.
2. The superi or cerebel l ar arteri es, w hich send branches t o t he cerebral
peduncles and brachium conjunct ivum bef ore supplying t he superior
cerebellum.
3. The posteri or choroi dal arteri es, w hich supply t he cerebral peduncles, t he
lat eral superior colliculi, t he t halamus, and t he choroid plexus of t he t hird
vent ricle.
4. The anteri or choroi dal arteri es (f rom t he int ernal carot ids or middle cerebral
art eries), w hich in some cases help supply t he cerebral peduncles as w ell as
supramesencephalic st ruct ures.
5. The posteri or cerebral arteri es, w hich also give rise t o some mesencephalic
branches.
Mesencephalic Syndromes
Ventral Cranial Nerve III Fascicular Syndrome (Weber's
Syndrome)
A lesion aff ect ing t he cerebral peduncle, especially t he medial peduncle, may
damage pyramidal f ibers and t he f ascicle of cranial nerve I I I [13] (Fig. 15-6).
This result s in t he Weber's syndrome, w hich consist s of t he f ollow ing:
1. Cont ralat eral hemiplegia (including t he low er f ace) due t o cort icospinal and
cort icobulbar t ract involvement
2. I psilat eral oculomot or paresis, including para-sympat het ic cranial nerve I I I
paresis (i. e. , dilat ed pupil)
This syndrome may be seen w it h int rinsic or ext rinsic brainst em lesions. When
supranuclear f ibers f or horizont al gaze are int errupt ed in t he medial peduncle, a
supranuclear-t ype conjugat e gaze palsy t o t he opposit e side may occur (the
mi dbrai n syndrome of Fovi l l e).
FI G URE 15-6 Diagram of a sect ion t hrough t he mesencephalon show ing
regions in w hich t he oculomot or nerve f ascicle may be injured, causing
specif ic neurologic syndromes.
Dorsal Cranial Nerve III Fascicular Syndromes

(Benedikt's Syndrome)
A lesion aff ect ing t he mesencephalic t egment um may aff ect t he red nucleus, t he
brachium conjunct ivum, and t he f ascicle of cranial nerve I I I (Fig. 15-6). More
vent ral t egment al lesions result in Benedi kt's syndrome, [76] w hich consist s of
t he f ollow ing:
1. I psilat eral oculomot or paresis, usually w it h a dilat ed pupil

2. Cont ralat eral involunt ary movement s, including int ent ion t remor, hemichorea,
or hemiat het osis, due t o dest ruct ion of t he red nucleus
Similar clinical manif est at ions are not ed w it h more dorsal midbrain t egment al
lesions (Fig. 15-6) t hat injure t he dorsal red nucleus and brachium conjunct ivum
(Cl aude's syndrome) but w it h prominent cerebellar signs (e. g. , asynergia,
at axia, dysmet ria, dysdiadochokinesia) and no hemiballismus[13] . The
Not hnagel's syndrome is a variant of t he dorsal midbrain syndrome (see
subsequent t ext ), and may not include a f ascicular t hird nerve palsy.
Dorsal M esencephalic Syndromes

Dorsal rost ral mesencephalic lesions produce mainly neuro-opht halmologic
abnormalit ies. The dorsal mesencephalic syndrome (also know n as t he Sylvian
aqueduct syndrome, t he Koeber-Salus-Elschnig syndrome, or Parinaud's
syndrome)[ 57] is most of t en seen w it h hydrocephalus or t umors of t he pineal
region. This syndrome includes all or some of t he f ollow ing signs:
1. Paralysis of conjugat e upw ard gaze (occasionally dow n-gaze)
2. Pupillary abnormalit ies (pupils are usually large w it h light -near dissociat ion)
3. Convergence-ret ract ion nyst agmus on upw ard gaze (especially elicit ed by
inducing upw ard saccades by a dow n-moving opt okinet ic t arget )
4. Pat hologic lid ret ract ion (Collier's sign)
5. Lid lag
6. During horizont al ref ixat ions, t he abduct ing eye may move more slow ly t han
t he adduct ing eye (“pseudoabducens palsy”), perhaps ref lect ing excess
convergence t one.
Top of the Basilar Syndrome

O cclusive vascular disease of t he rost ral basilar art ery, usually embolic,
f requent ly result s in t he “t op of t he basilar” syndrome [22, 80] due t o inf arct ion
of t he midbrain, t halamus, and port ions of t he t emporal and occipit al lobes. An
uncommon variant of t his syndrome may also result in bilat eral paramedian
midbrain ischemia[121] . This syndrome may also occur in pat ient s w it h giant
basilar art ery t ip aneurysms, in pat ient s w it h vasculit is, and af t er cerebral
angiography[ 80] . This syndrome variably includes t he f ollow ing:
1. Uni l ateral medi obasal i nf arcts. Unilat eral or bilat eral paralysis of upw ard or
dow nw ard gaze, disordered convergence, pseudoabducens palsy,
convergence-ret ract ion nyst agmus, ocular abduct ion abnormalit ies, elevat ion
and ret ract ion of t he upper eyelids (Collier's sign), skew deviat ion, and
light ning-like eye oscillat ions.
2. Uni l ateral medi obasal i nf arcts. Small and react ive, large or midposit ion and
f ixed, corect opia, occasionally oval pupil.
3. Uni l ateral medi obasal i nf arcts. Somnolence, sleep-w ake cycle abnormalit ies,
peduncular hallucinosis, memory diff icult ies, agit at ed delirium.
4. Uni l ateral medi obasal i nf arcts. Hemianopia, cort ical blindness, Balint 's
syndrome.
5. Uni l ateral medi obasal i nf arcts. Lesions causing pseudoabducens palsy w it h
convergence-ret ract ion nyst agmus have been f urt her mapped t o t he
midbrain-diencephalic junct ion[104] . I n addit ion, isolat ed unilat eral superior
oblique palsies have been described in pat ient s w it h cont ralat eral t egment al
lesions of t he t rochlear nucleus and adjacent int raaxial t rochlear nerve [131] .
Likew ise, isolat ed cranial nerve palsies have been report ed as t he sole
manif est at ion of small mesencephalic inf arct s[128] .
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137. Urban PP, Wicht S, Marx J, et al. I solat ed volunt ary f acial paresis due t o
pont ine ischemia. Neurol ogy 1998; 50: 1859–1862.
138. Venna N, Sabin TD. Universal dissociat ed anest hesia due t o bilat eral
brainst em inf arct s. Arch Neurol 1985; 42: 918–922.
139. Waespe W, Baumgart ner R. Enduring dysmet ria and impaired gain
adapt ivit y of saccadic eye movement s in Wallenberg's lat eral medullary
syndrome. Brai n 1992; 115: 1123–1146.
140. Waespe W, Wichmann W. O culomot or dist urbances during visual-

vest ibular int eract ion in Wallenberg's lat eral medullary syndrome. Brai n
1990; 113: 821–846.
141. Wat son SR, Colbach JG . Focal pat hological st art le f ollow ing pont ine
inf arct ion. Mov Di sord 2002; 17(1): 212–218.
> Table of C ontents > C hapter 16 - The C er ebellum
Chapter 16
The Cerebellum
Anatomy of the Cerebellum

The cerebellum (Fig. 16-1A and B), derived f rom t he somat ic aff erent port ion of
t he alar plat e (rhombic lip), act s as a monit or or modulat or of mot or act ivit y
“originat ing” in ot her brain cent ers. The cerebellum regulat es muscle t one,
post ure, and equilibrium. O ne of t he major cerebellar f unct ions is t he aut omat ic
excit at ion of ant agonist muscles at t he end of a movement , w it h t he simult aneous
inhibit ion of agonist muscles t hat init iat ed t he movement .
The cerebellum is locat ed in t he post erior f ossa of t he skull, dorsal t o t he pons
and medulla oblongat a and separat ed f rom t he occipit al lobes by t he t ent orium
cerebelli. O n axial and coronal planes, a midline port ion, t he vermi s, and t w o
lat eral port ions, t he cerebel l ar hemi spheres, can be recognized. The f alx
cerebelli part ially separat es bot h cerebellar hemispheres. The vermis is
development ally older and receives mainly spinocerebellar aff erent s, w hereas
t he hemispheres have more complex f iber connect ions. Sagit t al and coronal
planes display best t he t hree major component s of t he cerebellum, separat ed by
f issures t hat lie near t he axial plane: t he anteri or and posteri or l obes (divided by
t he primary f issure) and t he f l occul onodul ar l obe (separat ed f rom t he post erior
lobes by t he post erolat eral or post nodular f issures). The ant erior lobe comprises
lobules I t o V, t he post erior lobe, lobules VI t o I X, w hile t he f locculonodular lobe
comprises lobule X.
Funct ional neuroimaging st udies perf ormed on human volunt eers w it h noninvasive
magnet ic resonance imaging(MRI ) have show n a somat ot opic component of t he
cerebellar represent at ion of f oot , hand, and t ongue movement s[58] . For t he
hand, t he cent er of act ivat ion w as f ound in t he ipsilat eral ant erior lobe in t he
int ermediat e hemispheric port ion of t he Larsell lobules H I V–V. Foot movement s
act ivat ed areas w it hin t he ipsilat eral cent ral lobule, in t he Larsell lobules I I –I I I
medial and ant erior t o t he corresponding hand areas. Responses f or t ongue
movement s w ere less consist ent , but f ound post erior and lat eral t o t he hand
area, most ly at t he post erior border of t he ant erior lobe ext ending in part t o t he
Larsell lobules H VI –VI I [ 58] .
The cerebellum consist s of a superf icial cort ex (made up of f olia) surrounding
t he deep w hit e mat t er, and f our pairs of deep nuclei. The cort ex of t he
cerebellum is f olded int o t he cerebellar f olia. Hist ologically, t he cerebellar cort ex
has t hree layers: t he out er mol ecul ar l ayer, t he middle Purki nje cel l l ayer, and
t he innermost granul e cel l l ayer. The granul e cel l s are t he only excit at ory cells
in t he cerebellar cort ex. Five cell t ypes are dist ribut ed in t hese layers: (a) t he
out er basket cel l s and t he inner stel l ate cel l s in t he molecular layer, (b) Purki nje
cel l s arranged in a single row in t he Purkinje cell layer, and (c) granul e cel l s and
G ol gi cel l s in t he granule cell layer. Except f or t he Purkinje cells (project ion
neurons), w hose axons project out side t he cerebellum, all ot her cells are
int rinsic neurons and est ablish connect ions w it hin t he cerebellum (Fig. 16-2).
The w hit e mat t er of t he cerebellum is made up of int rinsic, aff erent , and eff erent
f ibers. I ncoming impulses t o t he cerebellum reach t he dendrit es and cell bodies
of numerous Purkinje cells. The aff erent f ibers f orm t he great er part of t he
cerebellar w hit e mat t er, and w hen ent ering t he cerebellum, segregat e int o one of
t hree f iber syst ems: climbing, mossy, or mult ilayered. The climbing f ibers are t he
t erminal f ibers of t he olivocerebellar t ract s and make mult iple (1, 000 t o 2, 000)
synapt ic cont act s w it h one Purkinje cell. The mossy f iber syst em
includes all ot her cerebellar aff erent t ract s except t hose t hat cont ribut e t o t he
climbing f ibers and t he mult ilayered syst em. I n cont rast t o t he climbing f iber
syst em t he mossy f iber syst em is diff use, having mult iple branches; so a single
mossy f iber may st imulat e t housands of Purkinje cells t hrough t he granule cell.
The mult ilayered f iber syst em includes aff erent s t o t he cerebellum f rom t he
hypot halamus, raphe nuclei, and locus ceruleus, and also project s int o t he
cerebellar cort ex and deep cerebellar nuclei[2] .
FI G URE 16-1 ( A and B) The cerebellum. Midsaggit al and axial sect ions
FI G URE 16-2 Schemat ic diagram of t he cerebellar cort ex
From an embryogenet ic, phylogenet ic, and f unct ional st andpoint , t he cerebellum
may also be subdivided int o t he archi cerebel l um, t he pal eocerebel l um, and t he
neocerebel l um[ 17] . The archicerebellum corresponds t o t he f locculonodular lobe
and is also called t he vesti bul ocerebel l um because it has a number of
connect ions w it h t he vest ibular syst em. I t also receives input f rom areas of t he
brain concerned w it h eye movement s [75, 76] . As a result of t hese connect ions,
t he vest ibulocerebellum plays a role in t he cont rol of body equilibrium and eye
movement s. The paleocerebellum consist s of t he vermis of t he ant erior lobe, t he
pyramis, t he uvula, and t he paraf locculus. Also know n as t he spi nocerebel l um
because it receives input mainly f rom t he spinal cord, it plays a role in t he
cont rol of muscle t one and t he axial and limb movement s. The neocerebellum
(cort icocerebellum), or cerebrocerebel l um, consist s of t he middle port ion of t he
vermis and most of t he cerebellar hemispheres. Because it receives project ions
f rom t he pons, it is also t ermed t he pontocerebel l um. The neocerebellum
project s f ibers t o t he cerebral cort ex t hrough t he t halamus, and plays a role in
t he planning and init iat ion of movement s, as w ell as t he regulat ion of f ine limb
movement s.
Four pairs of nuclei on each side of t he midline w it hin t he w hit e mat t er core of
t he cerebellum receive input f rom t he cerebellar cort ex and incoming aff erent s.
These nuclei are also t he main source of cerebellar eff erent s. All of t he eff erent
project ions of t he deep cerebellar nuclei are excit at ory, except f or project ions t o
t he inf erior olive, w hich are inhibit ory. From medial t o lat eral, t hese nuclei
include t he f asti gi al nucl eus, t he nucl eus gl obose (post erior int erposed), t he
nucl eus embol i f orm (ant erior int erposed), and t he dentate nucl eus (lat eral
cerebellar). O n t he basis of t he connect ions of t hese nuclei, t he cerebellum can
be longit udinally subdivided [16, 34] as f ollow s: (a) a midline (vermal) zone,
cont aining cerebellar neurons project ing t o t he f ast igial nucleus; (b) an
int ermediat e (paravermal) zone, cont aining neurons project ing t o t he nucleus
int erposed; and (c) a lat eral (hemisphere) zone, cont aining neurons project ing t o
t he dent at e nucleus.
There is separat e somat ot opic represent at ion w it hin each cerebellar nucleus,
w it h caudal part s ant erior, rost ral part s post erior, t runk lat eral, and limbs medial
[ 31, 86] . Each nucleus cont rols a diff erent t ype or mode of movement [31, 86] ,
as f ollow s:
1. The f ast igial nucleus assist s st ance and gait and cont rols muscles only in t he
modes of sit t ing, st anding, and w alking. Theref ore, f ast igial lesions may
cause abasia.
2. The nucleus int erposed assist s segment al ref lexes (e. g. , t hose concerned
w it h st abilit y) and speeds t he init iat ion of movement s t riggered by
somat osensory cues t hat guide t he response, st ops unw ant ed and promot es
w ant ed oscillat ions, and st abilizes holds. Theref ore, nucleus-int erposed
lesions may result in delayed check (rebound) responses, t runcal t it ubat ion,
abnormal rapid alt ernat ing movement s, act ion t remor, oscillat ion of t he
out st ret ched ext remit ies, and at axia on f inger-nose-f inger and heel-knee-shin
maneuvers.
3. The dent at e nucleus assist s in t asks requiring f ine dext erit y. Lesions of t his
nucleus or it s project ions cause delays in init iat ing and t erminat ing
movement s, t erminal and int ent ion t remor, t emporal incoordinat ion in
movement s t hat require mult iple joint s, and abnormalit ies in t he spat ial
coordinat ion of hand and f inger movement s.
The cerebellum is connect ed t o t he brainst em by t hree large cerebellar

peduncles: t he i nf eri or cerebel l ar peduncl e ( resti f orm body), t he mi ddl e
cerebel l ar peduncl e ( brachi um ponti s), and t he superi or cerebel l ar peduncl e
(brachi um conjuncti vum). Most aff erent f ibers t hat project t o t he cerebellum do
so t hrough t he inf erior and middle cerebellar peduncle, w hereas eff erent f ibers
f rom t he cerebellum t raverse t he superior and t he inf erior cerebellar peduncles.
The i nf eri or cerebel l ar peduncl e ( resti f orm body) connect s t he cerebellum t o t he
medulla oblongat a and carries aff erent and eff erent f ibers. Some aff erent f ibers
of clinical import ance include t he f ollow ing:
1. The dorsal spi nocerebel l ar tract, originat ing in t he dorsal nucleus of Clarke
(T1–L2), w hich carries propriocept ive and ext erocept ive inf ormat ion most ly
f rom t he t runk and ipsilat eral low er ext remit y.
2. The cuneocerebel l ar tract, originat ing in t he ext ernal arcuat e nucleus, w hich
t ransmit s
propriocept ive inf ormat ion f rom t he upper ext remit y and neck.
3. The ol i vocerebel l ar tract, w hich carries somat osensory inf ormat ion f rom t he
cont ralat eral inf erior olivary nuclei.
4. The vesti bul ocerebel l ar tract, w hich t ransmit s inf ormat ion f rom vest ibular
recept ors on bot h sides of t he body.
5. The reti cul ocerebel l ar tract, w hich arises in t he lat eral ret icular and
paramedian nuclei of t he medulla.
6. The arcuatocerebel l ar tract, w hich arises f rom t he arcuat e nuclei of t he
medulla oblongat a.
7. The tri gemi nocerebel l ar tract, w hich arises f rom t he spinal and main sensory
nuclei of t he t rigeminal nerve.
Eff erent f ibers in t he rest if orm body are mainly cerebellovest ibular pat hw ays and
const it ut e t he f asti gi obul bar tract, w hich courses in a separat e pat hw ay know n
as t he juxtaresti f orm body. O t her eff erent f ibers in t he inf erior cerebellar
peduncle are t he cerebel l oreti cul ar pathways.
The mi ddl e cerebel l ar peduncl e ( brachi um ponti s), t he largest of t he t hree
cerebellar peduncles, connect s t he cerebellum t o t he pons and carries mainly t he
aff erent f ibers of t he pont ocerebellar (cort icopont ocerebellar) t ract , w hich arises
in t he cont ralat eral pont ine gray mat t er and t ransmit s impulses f rom t he cerebral
cort ex t o t he int ermediat e and lat eral zones of t he cerebellum.
The superi or cerebel l ar peduncl e ( brachi um conjuncti vum) connect s t he
cerebellum t o t he midbrain. I t cont ains mainly cerebellar eff erent f ibers, alt hough
it also cont ains a f ew aff erent f ibers. Aff erent f ibers of t he superior cerebellar
peduncle include t he f ollow ing:
1. The ventral spi nocerebel l ar tract, w hich t ransmit s propriocept ive and
ext erocept ive inf ormat ion f rom levels below t he midt horacic cord.
2. The tectocerebel l ar tract, arising in t he superior and inf erior colliculi, w hich
carries audit ory and visual inf ormat ion.
3. The tri gemi nocerebel l ar tract, w hich carries propriocept ive f ibers f rom t he
mesencephalon and t act ile inf ormat ion f rom t he chief sensory nucleus of t he
t rigeminal nerve.
4. The cerul ocerebel l ar tract, w hich carries f ibers f rom t he nucleus ceruleus.
Ef f erent f ibers of t he superior peduncle include t he f ollow ing:
1. The dentatorubral tract, w hich carries out put t o t he cont ralat eral red nucleus.
Many of t he f ibers ending in t his nucleus are branches of t he larger
dent at ot halamic t ract .
2. The dentatothal ami c tract, w hich t ransmit s out put t o t he cont ralat eral
vent rolat eral nucleus of t he t halamus.
3. The unci nate bundl e of Russel l, w hich carries out put t o t he vest ibular nuclei
and ret icular f ormat ion.
Vascular Supply of the Cerebellum

The blood supply t o t he cerebellum is derived f rom t he post erior inf erior
cerebellar art eries, t he ant erior inf erior cerebellar art eries, and t he superior
cerebellar art eries (Fig. 16-3) [3, 70] . The branches of t hese t hree vessels
anast omose w it h branches f rom t he corresponding vessels on t he opposit e side
t o provide a rich anast omot ic net w ork.
1. The Posteri or Inf eri or Cerebel l ar Artery ( PICA) arises f rom t he int racranial
vert ebral art ery and supplies t he lat eral medullary t egment um, inf erior
cerebellar peduncle, t he ipsilat eral port ion of t he inf erior vermis, and t he
inf erior surf ace of t he cerebellar hemisphere. The medial branch of t he PI CA
supplies t he medial cerebellum and t he dorsolat eral medulla oblongat a, and
t he lat eral branch supplies t he inf eropost erolat eral aspect of t he cerebellum,
but not t he medulla.
2. The Anteri or Inf eri or Cerebel l ar Artery ( AICA), w hich of t en arises about 1
cm above t he origin of t he basilar art ery, most f requent ly as a single vessel,
provides supply t o t he ant erior pet rosal surf ace of t he cerebellar
hemisphere, f locculus, low er port ion of t he middle cerebellar peduncle, and
lat eral pont omedullary t egment um.
3. The superi or cerebel l ar artery arises near t he dist al segment of t he basilar
art ery just below t he t erminal bif urcat ion int o t he paired post erior cerebral
art eries, and supplies t he upper surf ace of t he cerebellar hemisphere,
ipsilat eral port ion of t he superior vermis, most of t he dent at e nucleus, upper
port ion of t he middle cerebellar peduncle, superior cerebellar peduncle, and
lat eral pont ine t egment um.
Clinical M anifestations of Cerebellar Dysfunction

The classic report of G ordon Holmes describes cerebellar dysf unct ion in pat ient s
w it h w ound injuries t o t he cerebellum [38, 39] . The cerebellum cont rols t he rat e,
direct ion, range, and f orce of volunt ary movement s, and t hrough it s vest ibular
connect ions, correct s and adjust s t he individual's upright posit ion in space. Thus,
cardinal f eat ures
of cerebellar dysf unct ion involve dist urbances in mot or cont rol, muscle t one
regulat ion, and coordinat ion of skilled movement s, and are brief ly discussed
here.
FI G URE 16-3 Course of t he cerebellar art eries. SCA = superior cerebellar
art ery; AI CA = ant erior inf erior cerebellar art ery; PI CA = post erior inf erior
cerebellar art ery. (Adapt ed f rom Amarenco P. The spect rum of cerebellar
inf arct ions. Neurol ogy 1991; 41: 973–979, w it h permission. )
Hypotonia
Hypot onia accompanies acut e hemispheric lesions and is seen less of t en w it h
chronic lesions. The hypot onia is ipsilat eral t o t he side of t he cerebellar lesion
and is of t en more not iceable in t he upper limbs, part icularly in t he proximal
musculat ure. Hypot onic ext remit ies have decreased resist ance t o passive
st ret ching of t he muscles and of t en exhibit pendular muscle st ret ch ref lexes,
w hich may also be diminished. O ccasionally, cerebellar lesions may be
associat ed w it h increased t one of t he ext remit y due in part t o secondary
brainst em (cort icospinal t ract ) compression. Hypot onia occurs only w it h
neocerebellar lesions and is probably t he result of decreased f usimot or act ivit y
secondary t o cerebellar injury, especially t o t he dent at e nucleus, result ing in a
decreased response t o st ret ch in t he muscle spindle aff erent s.
Ataxia or Dystaxia
Cerebellar disorders result principally f rom def ect ive t iming of sequent ial
cont ract ions of agonist and ant agonist muscles[33] . At axia, regarded as t he
“cerebellar sign par excellence, ” ref ers t o a dist urbance in t he smoot h
perf ormance of volunt ary mot or act s causing muscular incoordinat ion or impaired
balance[ 18] . The movement s err in speed, range, f orce, and t iming. I n t he
absence of cerebellar inhibit ory and modulat ing inf luences, skilled movement s
originat ing in t he cerebral mot or cort ex become inaccurat e and poorly cont rolled.
At axia may aff ect t he limbs, t he t runk, or gait . Present at ion may be acut e (e. g. ,
cerebellar hemorrhage, biot inidase def iciency, phenyt oin int oxicat ion, acut e
cerebellar at axia f ollow ing chickenpox); episodic or recurrent (e. g. ,
channelopat hies, basilar art ery migraine, Hart nup's disease), or chronic
progressive or non-progressive (e. g. , cerebellar t umors, Spinocerebellar
At axias[ SCA] , Friedreich's at axia, at axia t elangiect asia, hypot hyroidism, et c. )
(Tables 16-1, 16-2, and 16-3) [28, 36, 43, 69, 82] . I nherit ed at axias comprise a
het erogeneous group of disorders charact erized by variable combinat ions of
progressive degenerat ion of t he cerebellum and spinocerebellar t ract s
associat ed w it h clinical manif est at ions of pyramidal, ext rapyramidal and
peripheral nervous syst em dysf unct ion, and cerebellar or olivopont ocerebellar
at rophy on neuroimaging st udies. Heredit ary at axias are f urt her classif ied int o
aut osomal dominant , aut osomal recessive, and X-linked f orms. Aut osomal
dominant cerebellar at axias t ypically
present in adult hood, and are current ly classif ied as SCA 1–25 according t o t he
specif ic gene or chromosomal locus associat ed w it h t hese disorders[73] . Tw o of
t hese SCAs are brief ly described here. Clinical f eat ures suggest ive of SCA 3
(Machado-Joseph disease) include progressive cerebellar at axia, nyst agmus,
opht halmoplegia, f acial f asciculat ions, f acial dyst onias, eyelid ret ract ion w it h
bulging eyes, and parkinsonism[74] . Feat ures suggest ive of
dent at orubropallidoluysian at rophy encompass cerebellar at axia, myoclonus,
choreoat het osis, dyst onia, parkinsonism, psychiat ric dist urbances, epilepsy and
dement ia[ 57] .
TABLE 16-1 Causes of Acute Ataxia
Idiopathic (“acute cerebellar ataxia”)

Metabolic
Hypoglycemia
Hyponatremia
Hyperammonemia
Biotinidase deficiency
Infections
Bacterial meningitis
Viral meningitis
Toxins
Trauma (battered child)
Hydrocephalus
Cerebellar lesions
Neoplasm (primary or metastatic)
Infarct
Hemorrhage
Neuroblastoma
Polyradiculoneuropathy
GBS
Fisher variant of GBS
Tick paralysis
“Labyrinthitis”
Brainstem tumors
Multiple sclerosis
GBS = Guillain-Barré syndrome.
TABLE 16-2 Causes of Episodic/Recurrent Ataxia
Channelopathies
Episodic ataxia Type 1
Episodic ataxia Type 2
Paroxysmal choreoathetosis with episodic ataxia
Periodic vestibulocerebellar ataxia
Familial hemiplegic migraine
Basilar artery migraine
Benign paroxysmal vertigo of childhood
Epilepsy (post-ictal state)
Toxins
Metabolic
Hypoglycemia
Hyperammonemia
Organic acid disorders
Hartnup disease
Hyperpyruvic acidemias
Pyruvate decarboxylate deficiency
Refsum disease
Porphyria
Leigh syndrome
Maple syrup urine disease
Congenital lactic acidosis
Dominant paroxysmal ataxia
Aut osomal recessive at axias t ypically result in early onset cerebellar at axia
associat ed w it h various neurologic, opht halmologic, and syst emic manif est at ions.
Pat hologically charact erized by t he degenerat ion of t he spinocerebellar t ract s,
dorsal columns, and t o a lesser ext ent , t he cort icospinal t ract s, Friedreich's
at axia, t he most common of t he aut osomal recessive at axias, is dist inguished by
progressive limb and gait at axia, dysart hria, rhyt hmic head t remor, aref lexia of
knee and ankle jerks, axonal polyneuropat hy, ext ensor plant ar responses, opt ic
at rophy, cardiomyopat hy, diabet es, pes cavus, and kyphoscoliosis[27] . At axia
secondary t o cerebellar injury charact erist ically persist s in spit e of visual cues
(unlike sensory at axia w hich is more pronounced w it h eyes closed).
The t erm ataxi a includes ot her abnormalit ies of volunt ary movement cont rol, such
as asynergi a (lack of synergy of t he various muscle component s in perf orming
more complex movement s so t hat movement s are disjoint ed and clumsy and
broken up int o isolat ed successive part s), dysmetri a (abnormal range, f orce and
excursions in movement ), dysdi adochoki nesi a (impaired perf ormance of rapidly
alt ernat ing movement s), and past -point ing. Dysmet ria is best appreciat ed w it h
t he f inger-nose t est , or in t he case of t he low er ext remit ies, heel-knee-shin or
great t oe-t o-examiner's f inger t est . The f inger-nose t est may show a t endency t o
f all short or overshoot t he examiner's f inger (past -point ing). The heel-knee-shin
t est may reveal a w avering of t he heel aw ay f rom t he line of t he shin. When an
opposed mot ion is suddenly released, an impaired checking response and an
excessive rebound phenomenon are also involved.
G ait dist urbance is one of t he most disabling manif est at ions of cerebellar
disease. Typically, pat ient s w it h cerebellar disease have a w ide-based st ance
and a gait [32] w it h increased t runk sw ay, irregular st epping w it h a t endency t o
st agger as if int oxicat ed, and impaired t andem w alking and t andem gait
paradigm w it h inappropriat e t iming of f oot placement [80] . Truncal inst abilit y may
be manif est ed by f alls in any direct ion. Truncal at axia and t it ubat ions suggest a
midline cerebellar lesion.
Cerebellar Dysarthria
Dysart hria occurring w it h cerebellar disease is generally charact erized by
abnormalit ies in art iculat ion and prosody [23, 34] . These t w o
abnormalit ies may occur t oget her or independent ly. Speech product ion is of t en
labored w it h occasional excessive f acial grimacing. Comprehension remains
int act . Cerebellar dysart hria has been described as scanning, slurred, st accat o,
explosive, hesit ant , slow alt ered accent , and garbled speech[67] . The dysart hria
may be a result of a generalized hypot onia, and may aff ect int onat ion rat her t han
art iculat ion[ 42] . The development of agrammat ic speech af t er right cerebellar
inf arct ion support s t he hypot hesis t hat t he cerebellum provides t emporal
int erplay among t he neural st ruct ures underlying t he processes responsible f or
t he product ion of sent ences[77] .
TABLE 16-3 Causes of Chronic Ataxia
Fixed deficit
Cerebral palsy
Malformations (i.e., Dandy-W alker, Chiari,
rhomboencephalosynapsis, cerebellar agenesis,
hypoplasia of the cerebellar vermis, familial agenesis of
the cerebellar vermis, pontocerebellar hypoplasia,
Joubert's syndrome, cerebellar cortical malformations,
macrocerebellum, etc.) γ-glutamyl-cysteine synthetase
deficiency
Triosephosphate isomerase deficiency
Chediak-Higashi disease
Autosomal dominant
SCA1
SCA2
SCA3 (MJD)
SCA4
SCA5
SCA6
DRPLA
SCA7 (Ataxia/retinal degeneration)
SCA8
SCA 9 (not assigned)
SCA 10
SCA 11
SCA 12
SCA 13
SCA 14
SCA 15 (genetic locus not yet identified)
SCA 16
SCA 17
SCA 18–21 (not yet published, but registered)
SCA 22
SCA 25
Autosomal recessive
Friedreich's ataxia
Early onset cerebellar ataxia with retained muscle
stretch reflexes
Ataxia with vitamin E deficiency
Ataxia with oculomotor apraxia
W ith hypogonadism
W ith myoclonus (Ramsay Hunt syndrome)
Infantile onset spinocerebellar ataxia
W ith pigmentary retinopathy
W ith optic atrophy ± mental retardation (including
Behr syndrome)
W ith cataract and mental retardation
(Marinesco-Sjögren syndrome)
W ith childhood deafness
W ith extrapyramidal features
Autosomal recessive late onset cerebellar ataxia
Autosomal recessive spastic ataxia of
Charleroix-Saguenay
Ataxia telangiectasia
W ilson's disease
Refsum's disease
Bassen-Kornzweig disease (abetalipoproteinemia)
Spinocerebellar ataxia with axonal neuropathy
Inborn errors of metabolism
Cerebrotendinous xanthomatosis
Other inherited disorders
Sphingolipidoses
Ceroid-lipofuscinosis
X-Linked spinocerebellar ataxia
Acquired diseases
Hypothyroidism
Drugs or toxins
Multiple sclerosis
Neoplasms
Hamartomatous malformations (i.e., dysplastic
gangliocystoma or Lhermitte-Duclos disease)
Erdheim-Chester disease
Paraneoplastic cerebellar degeneration (anti-Yo, anti-
Hu, anti-Ri, anti-Tr, anti-CV2, antibody-negative)
Autoimmune cerebellar ataxia
Gerstmann-Sträussler-Scheinker disease
SCA = spinocerebellar ataxia; MJD = Machado-Joseph

disease; DRPLA = dentatorubropallidoluysian atrophy.
Funct ional MRI st udies among healt hy volunt eers have show n t hat t he cerebellar
represent at ion of t he t ongue and oral f acial muscles corresponds t o t he areas
involved in pat ient s w it h cerebellar dysart hria. I n a series of 162 cases of f ocal
cerebellar disease, 31 pat ient s had dysart hria, of w hom 22 had predominant ly or
exclusively lef t hemispheric lesions[46] . Cerebellar hemispheric lesions w ere
associat ed w it h speech disorders more of t en t han vermal lesions. Dysart hria
w as especially evident af t er damage ext ending int o t he superior paravermal
segment of t he lef t cerebellar hemisphere. Because cerebrocerebellar
connect ions are predominant ly cont ralat eral, and t he nondominant cerebral
hemisphere is concerned w it h prosody of speech [46, 67] , t he aut hors concluded
t hat t he dominance of t he lef t cerebellar hemisphere in t he regulat ion of speech
(melody and cont inuit y) may be due t o t his hemisphere accessing t he
nondominant cerebral hemisphere. Conf irming t he import ance of t he superior
cerebellum in voice cont rol, ot her aut hors have f ound dysart hria, charact erized
by irregularly dist ribut ed art iculat ory def icit s and slow ed speech t empo, t o be as
common w it h right -sided as w it h lef t -sided lesions[2] . Silveri et al. report ed a
pat ient w it h agrammat ical speech af t er a PI CA t errit ory inf arct ion, suggest ing a
right cerebellar hemispheric dominance f or language f unct ion [77] . Isol ated
cerebellar dysart hria, w it hout any ot her def icit , has also been report ed w it h a
small inf arct in t he lef t paravermal zone of t he rost ral cerebellum (lobulus
simplex and semilunaris superior) in t he t errit ory of t he medial branch of t he
superior cerebellar art ery[4] , w it h right paravermal segment inf arct s, w it h
lesions in t he upper paravermal area of t he right cerebellar hemisphere[88] , as
w ell as w it h an int act dent at e nucleus[1] .
Transi ent muti sm af ter exci si on of cerebel l ar tumors (vermian neoplasms) has
been increasingly recognized af t er post erior f ossa surgery in children. Whet her
t his syndrome is t umor specif ic or not remains debat able. Sympt oms usually
develop one t o t hree days af t er surgery. I n many inst ances, t hese children also
have oropharyngeal apraxia, w it h diff icult y init iat ing t he chew ing and sw allow ing
process, global impairment in t he init iat ion of volunt ary act ivit y, impaired eye
opening, and urinary ret ent ion[62] . I t has been speculat ed t hat t ransient bilat eral
involvement of t he dent at o-rubro-t halamic t ract may lead t o t his st at e of mut ism
and subsequent dysart hria [19, 30, 63, 65, 89, 90] . O t her neurologic lesions
know n t o cause mut ism include damage t o Broca's area, damage t o t he
supplement ary mot or area, bilat eral damage t o t he ret icular f ormat ion of t he
mesencephalon (akinet ic mut ism), t he locked-in syndrome and chronic veget at ive
st at e, Marchiaf ava-Bignami disease, severe pseudobulbar palsy due t o diff use
bilat eral cerebral hemispheric dysf unct ion, bilat eral t halamic damage f ollow ing
t halamot omy f or Parkinson's disease, corpus callosot omy, surgical resect ion of
t he supplement ary mot or cort ex of t he dominant hemisphere, and bilat eral
pharyngeal or vocal cord paralysis (e. g. , due t o bulbar poliomyelit is or G uillain-
Barré syndrome) [15, 25] .
Tremor
Lesions of t he cerebellum, especially t hose aff ect ing t he dent at e nucleus, induce
a ki neti c ( i ntenti on) tremor occurring during act ivit y. A st at ic (post ural) t remor
may also occur. Lesions of t he dent at e nucleus may result in t remor because
t hey int errupt a rubro-olivo-cerebellar circuit [44] . Pat ient s w it h Wilson disease
may have t remor or at axic dysmet ria. Cerebellar disease may also be
associat ed w it h cerebellar f it s; t hese are episodes of decerebrat e rigidit y
usually seen w it h large midline cerebellar mass lesions[93] .
Ocular Motor Dysfunction

Nyst agmus is f requent ly observed in associat ion w it h cerebellar disorders. G aze-
evoked, upbeat , rebound, and abnormal opt okinet ic nyst agmus may be seen w it h
midline cerebellar lesions [29, 34] . Periodic alt ernat ing nyst agmus is seen w it h
lesions of t he uvula and nodulus or w it h lesions involving t heir connect ions w it h
t he brainst em vest ibular nuclei. Dow nbeat nyst agmus may also occur w it h
post erior midline cerebellar lesions involving t he vest ibulocerebellum[48] .
Posit ional nyst agmus, mimicking posit ional nyst agmus of t he benign paroxysmal
t ype, may occur in pat ient s w it h post erior f ossa t umors. O cular dysmet ria [22] —
a conjugat e overshoot and undershoot of a t arget w it h volunt ary saccades—may
be seen w it h midline[75] or lat eral[64] cerebellar lesions. O t her ocular signs
seen w it h cerebellar disorders include irregular t racking, saccadic breakdow n of
pursuit , ocular f lut t er, opsoclonus, ocular bobbing, paresis of conjugat e gaze,
square w ave jerks at rest , skew deviat ion, and f ailure t o suppress t he vest ibulo-
ocular ref lex[35] . Because most of t he disorders t hat give rise t o t hese
abnormalit ies also aff ect ot her brainst em st ruct ures, t he cerebellar role in t heir
genesis has not been f ully def ined. I n general, most “cerebellar” eye signs
cannot be precisely localized t o specif ic areas of t he cerebellum. (See Chapt er 8
f or a discussion of cerebellar cont rol of eye movement s. )
Nonmotor Manifestations
Cerebellar lesions in animals may result in dist urbances of emot ion, behavior,
and mot or learning. A grow ing body of dat a also gives credence t o t he proposed
cont ribut ion of t he cerebellum t o t he modulat ion of a variet y of nonmot or
cognit ive and behavioral processes in humans [26, 49, 50, 53, 54] . I n aut ism,
post mort em hist opat hologic st udies have show n marked hypoplasia w it hin t he
cerebellar vermis and variable loss of Purkinje cells t hroughout t he cerebellar
hemispheres and archicerebellum. Abnormalit ies have also been f ound in t he
f ast igial and int erposed nuclei, w hereas t he ant erior lobe of t he cerebellum and
vermis have not been involved [13, 24, 53] . Bipolar disorders w ere also not ed in
3 of 15 subject s af t er f ocal cerebellar lesions; lesions included right cerebellar
hypoplasia, bilat eral cerebellar at rophy, and lef t midbrain pat hology[45] . A
cerebel l ar cogni ti ve af f ecti ve syndrome, charact erized by impaired execut ive
f unct ioning, personalit y changes associat ed w it h blunt ed eff ect or disinhibit ed
and inappropriat e behavior, visuo-spat ial disorganizat ion, impaired visual-spat ial
memory, mild anomia, agrammat ism, and dysprosodia, has been report ed [72] .
The neurobehavioral present at ion w as more evident in t hose pat ient s w it h
pancerebellar disease and in t hose w it h acut e onset cerebellar disease. Lesions
of t he post erior lobe w ere part icularly responsible f or t he dist urbed cognit ive
behaviors in t he generat ion, w hereas t he cerebellar vermis w as more
consist ent ly involved in pat ient s w it h a more pronounced aff ect ive
sympt omat ology. The ant erior lobe of t he cerebellum has not been implicat ed t o
t he same ext ent in t he generat ion of t hese cognit ive/ behavioral manif est at ions
[ 71, 72] . A disrupt ion of t he cerebellar modulat ion of neural circuit s linking
pref ront al, post erior pariet al, superior t emporal, and limbic cort ices w it h t he
cerebellum has been proposed as t he mechanism f or t his syndrome. O n t he
basis of t he several reciprocal anat omic connect ions bet w een t he cerebral
cort ex and cerebellum, t his appears t o be a plausible explanat ion. More recent ly,
lesions in t he cerebro-pont o-cerebellar pat hw ays have been proposed as a
plausible anat omical sit e f or pat hological laught er and crying[60] . Cont ralat eral
cerebellar hypomet abolism has been not ed among aphasic pat ient s w it h lef t
cerebral inf arct s or hemorrhages[37] . Cerebellar disease may be associat ed
w it h macrographia. I n addit ion, t ypical f eat ures of spat ial dysgraphia, w it h
omission and repet it ion of st rokes and let t ers, have been described in a pat ient
w it h marked cerebellar at rophy (cerebellar hemispheres more involved t han t he
vermis) associat ed w it h diff use cort icosubcort ical at rophy[78] . A discoordinat ion
bet w een planning of t he movement and perf ormance, due t o a lack of t he
cerebellar modulat ion bet w een premot or cort ex and propriocept ive aff erence
during t he ongoing handw rit ing, has been post ulat ed as an explanat ion f or t his
observat ion[ 78] .
Cerebellar Syndromes
I n general, disorders predominant ly involving t he midline cerebellum aff ect
primarily t he t runcal musculat ure and body equilibrium. I n cont rast , disorders
aff ect ing primarily t he cerebellar hemispheres have an ipsilat eral impairment of
t he volunt ary movement s of t he f ingers and legs as t heir most salient def icit . The
cerebellar syndromes may be divided as f ollow s:
1. The rost ral vermis syndrome (ant erior lobe)

2. The caudal vermis syndrome (f locculonodular and post erior lobe)
3. The hemispheric syndrome (post erior lobe, variably ant erior lobe)
4. The pancerebellar syndrome (all lobes)
Rostral Vermis Syndrome

The clinical charact erist ics of t his syndrome include t he f ollow ing:
1. A w ide-based st ance and t it ubat ing gait

2. At axia of gait , w it h proport ionally lit t le at axia on t he heel-t o-shin maneuver
w it h t he pat ient lying dow n
3. Normal or only slight ly impaired arm coordinat ion
4. I nf requent presence of hypot onia, nyst agmus, and dysart hria
This syndrome is best exemplif ied by t he rest rict ed f orm of cerebellar cort ical
degenerat ion t hat occurs w it h unknow n prevalence in t he alcoholic
populat ion[ 91] . There is select ive at rophy of t he ant erior and superior vermis,
part icularly t he superf icial f olia, w it h lesser involvement of t he caudal vermis,
ant erior part s of lat eral lobes, f locculus, and paraf locculus. Morphomet ric
met hods have f urt her demonst rat ed a remarkable Purkinje cell loss and densit ies
especially in lobules I –I V, I X, and X of t he vermis[20] . Clinically, t hese pat ient s
present w it h incoordinat ion of gait of t he legs w it h lit t le involvement of t he arms,
speech, or ocular mot ilit y.
Caudal Vermis Syndrome

The clinical charact erist ics of t his syndrome include t he f ollow ing:
1. Axial disequilibrium and st aggering gait
2. Lit t le or no limb at axia

3. Somet imes spont aneous nyst agmus and rot at ed post ures of t he head
This syndrome is t ypically seen w it h disease processes t hat damage t he

f locculonodular lobe, especially medulloblast oma in children. Medulloblast omas
account f or approximat ely 20% of pediat ric brain t umors. As t hese t umors grow,
a hemispheric cerebellar syndrome may be superimposed due t o neocerebellar
involvement . Met ast asis may occur t hroughout t he craniospinal axis. Pat ient s
w it h t umors in eit her t he vermis or t he cerebellar hemispheres may present w it h
sympt oms and signs of increased int racranial pressure.
Surgical t ransect ion of t he post erior inf erior cerebellar vermis may result in
marked impairment of t andem gait w it h minimal impairment of regular gait ,
st anding, and hopping on one f oot . Visually guided limb movement s and speech
remain unaff ect ed. Surgical disrupt ion of t he parallel f ibers crossing t he midline
cerebellar cort ex may be a crit ical variable account ing f or t hese clinical f eat ures
know n as t he posteri or vermal spl i t syndrome[ 12] .
Cerebellar Hemispheric Syndrome

Pat ient s w it h t his syndrome t ypically show incoordinat ion of ipsilat eral
appendicular movement s, part icularly w hen t hey require f ine mot or coordinat ion.
Thus, it aff ect s mainly muscles closely cont rolled by t he precent ral cort ex, such
as t hose involved in speech and f inger movement s. The most likely et iologies of
a cerebellar hemispheric syndrome include inf arct s, neoplasms, and
abscesses[ 34] .
Pancerebellar Syndrome
This syndrome, a combinat ion of all ot her cerebellar syndromes, is charact erized
by bilat eral signs of cerebellar dysf unct ion aff ect ing t he t runk, limbs, and cranial
musculat ure. I t is seen w it h inf ect ious and parainf ect ious processes,
hypoglycemia, hypert hermia, paraneoplast ic cerebellar degenerat ion associat ed
w it h small cell lung cancer (ant i-Hu ant ibodies), breast and ovarian carcinomas
(ant i-Yo ant ibodies), or Hodgkin's lymphoma (Tr ant ibodies) and ot her t oxic-
met abolic disorders[92] .
G ilman has suggest ed t hat , f or localizat ion purposes, t he cerebellum should be
view ed as a sagit t ally orient ed st ruct ure cont aining t hree zones: midline,
int ermediat e, and lat eral [32, 34] . The midline zone encompasses t he ant erior
and post erior part s of t he vermal cort ex, t he f ast igial nucleus, and t he
associat ed input and out put project ions. Many of t hese project ions are
concerned w it h post ure, locomot ion, t he posit ion of t he head in relat ion t o t he
t runk, and t he cont rol of ext raocular movement s. Thus, cerebellar signs result ing
f rom midline cerebellar disease are charact erized by disorders of st ance and
gait , t runcal t it ubat ion, rot at ed post ures of t he head, and dist urbances of eye
movement s. The int ermediat e zone consist s of t he paravermal region of t he
cerebellar cort ex and t he int erposed nuclei on each side. Neuronal act ivit y in t his
region appears t o be involved in t he cont rol of movement velocit y, f orce, and t he
pat t ern of muscle act ivit y, but clinical disorders relat ed t o disease of t his zone
have not been clearly delineat ed. The lat eral zone consist s of t he cerebellar
hemisphere and t he dent at e nucleus of each side. Neural unit s in t his zone are
involved in t he planning of movement s in connect ion w it h neurons in t he
precent ral region of t he cerebral cort ex; lesions result in abnormalit ies relat ed t o
volunt ary movement s and include hypot onia, dysart hria, dysmet ria,
dysdiadochokinesia, excessive rebound, impaired check response, kinet ic and
st at ic t remors, decompensat ion of movement s, past -point ing, and eye movement
abnormalit ies [32, 34] .
Syndromes of Cerebellar Infarction

Cerebellar inf arct s result f rom t hrombot ic or embolic occlusion of a cerebellar
vessel. The clinical manif est at ions and result ing def icit s are relat ed t o t he
specif ic vessels involved and t he ext ent of collat eral circulat ion. Main sympt oms
include vert igo, dizziness, nausea, vomit ing, gait unst eadiness, limb clumsiness,
headache, dysart hria, diplopia, and decreased level of alert ness. Most prominent
signs include limb and gait at axia, dysart hria, nyst agmus, and alt ered ment al
st at us. According t o t heir t opographical dist ribut ion, f our t ypes of cerebellar
inf arct ion are recognized corresponding t o t he art erial t errit ories of (a) t he PI CA
(40%), (b) t he AI CA (5%), (c) t he superior cerebellar art ery (35%), and (d) t he
cort ical w at ershed and deep cerebellar w hit e mat t er borderzone inf arct s (20%)
[ 10, 87] . Pragmat ically, t w o dist inct clinical syndromes are recognized:
cerebellar inf arct s w it h f ourt h vent ricular and brainst em compression and
cerebellar inf arct s w it hout f ourt h vent ricular or brainst em compression.
Large cerebel l ar i nf arcts likely t o cause brainst em compression may present
w it h sudden onset of occipit al headache, vert igo, nausea, vomit ing, gait
unst eadiness, and dysart hria[3] . Pat ient s of t en
display gait and t runcal at axia, ipsilat eral axial lat eropulsion, or bot h, w hich
usually prevent t hem f rom st anding upright [3] . They may also exhibit nyst agmus,
ipsilat eral limb dysmet ria, dysart hria, and impaired consciousness[85] . The
edemat ous cerebellum may compress t he aqueduct of Sylvius or t he f ourt h
vent ricle causing acut e obst ruct ive hydrocephalus, or may compress t he
brainst em result ing in increasing headaches, decreased level of alert ness, and
occasionally a head t ilt [3, 47] .
Tw o dist inct syndromes of cerebellar t issue herniat ion are recognized:
descending or t onsillar herniat ion syndrome, and upw ard or t ranst ent orial
herniat ion syndrome. Wit h a cerebellar pressure cone, t here is dow nw ard
displacement of t he cerebellar t onsils t hrough t he f oramen magnum causing
compression of t he medulla oblongat a. Clinical manif est at ions of t onsillar
herniat ion include neck st iff ness, parest hesias in shoulders, opist ot honus,
cardiac and respirat ory rhyt hm dist urbances, leading t o apnea and possible
deat h. Wit h upw ard t ranst ent orial herniat ion, t here is upw ard displacement of t he
superior aspect of t he cerebellar hemisphere t hrough t he f ree edge of t he
t ent orial incisura, result ing in midbrain compression. Clinical manif est at ions of
upw ard cerebellar herniat ion include let hargy, coma, paralysis or upw ard gaze,
mid-posit ion and unreact ive pupils, and abnormal ext ensor post uring. Large
cerebellar inf arct s t end t o involve t he t errit ory of t he PI CA, t he t errit ory of t he
superior cerebellar art ery, or bot h [3, 6] . Delayed alt erat ion in t he level of
consciousness may occur hours t o days af t er t he onset of ischemic sympt oms
eit her in isolat ion or in associat ion w it h t he w orsening of ot her neurologic signs
[ 3, 6] . Emergency surgery (e. g. , vent riculost omy or post erior f ossa
decompression or bot h) is of t en required.
The ot her end of t he clinical spect rum includes very small (border zone)
cerebellar inf arct s not easily localizable w it hin w ell-def ined art erial
boundaries[ 7] . I n a st udy of 47 pat ient s, Amarenco et al. at t ribut ed t he
mechanisms of t hese small cerebellar inf arct ions t o: global hypoperf usion
secondary t o cardiac arrest (4%), small or end (pial) art ery disease due t o
int racranial at heroma or hypercoagulable st at es (20%), f ocal cerebellar
hypoperf usion due t o large art ery vert ebrobasilar occlusive disease (34%), or
brain embolism (23%). I n nine pat ient s (19%), t he mechanism of inf arct ion w as
unknow n. Physical f indings w ere eit her absent or included a w ide-based gait ,
lat eropulsion, mild ipsilat eral dysmet ria, dysart hria, or dysdiadochokinesia[7] .
Acut e isolat ed hemiat axia is, in most cases, due t o inf rat ent orial (cerebellar)
st roke. How ever, suprat ent orial st roke (e. g. , t halamic inf arct ion ext ending int o
t he adjacent post erior limb of t he int ernal capsule and inf arct ion or hemorrhage
rest rict ed t o t he post erior limb of t he int ernal capsule) may also cause isolat ed
hemiat axia due t o int errupt ion of t he cerebellar pat hw ays at t he level of t he
int ernal capsule[52] .
Inferior Cerebellar Infarct (Posterior Inferior Cerebellar

Artery)
Most sympt omat ic cerebellar inf arct ions occur in t he t errit ory supplied by t he
PI CA. I nf arct s st emming f rom occlusion in t he t errit orial supply of t he PI CA are
described in Chapt er 21. Most of t en, inf arct s in t his art erial t errit ory result f rom
occlusion of t he dist al vert ebral art ery bef ore t he origin of t he PI CA. PI CA or
medial PI CA t errit ory inf arct s cause acut e vert igo and t runcal at axia, w hereas
lat eral PI CA t errit ory inf arct s cause unst eadiness, limb at axia, and dysmet ria
w it hout dysart hria. Unilat eral limb at axia w it hout dysart hria or vest ibular signs or
sympt oms suggest s an inf arct isolat ed t o t he t errit ory of t he lat eral branch of
t he PI CA[11] . Rarely, pat ient s may develop f ailure of aut omat ic breat hing w hen
asleep (O ndine's curse)[ 51] . Pat ient s may also present w it h isolat ed vert igo
resembling acut e labyrint hit is. Cardiac embolism, at herot hrombosis, and
vert ebral art ery dissect ion are t he main causes of large PI CA t errit ory
inf arct s[ 10] .
Ventral Cerebellar Infarct (Anterior Inferior Cerebellar

Artery)
I nf arct s in t he dist ribut ion of t he AI CA t errit ory involve t he lat eral mid- and low -
pont ine region and t he ant erolat eral part of t he cerebellum, part icularly t he
middle cerebellar peduncle, f locculus, and t he ant erior part of t he cerebellar
lobules, w it h t he except ion of t he lobulus ant erior[3] . Because of t he variabilit y
of t he AI CA, not all syndromes caused by it s occlusion are expect ed t o be
ident ical. The charact erist ic clinical pict ure of an AI CA inf arct consist s of t he
f ollow ing const ellat ion of sympt oms and signs [3, 4, 5, 8, 59, 83, 87] :
1. Prominent vert igo, nausea, vomit ing, and nyst agmus w ere not ed (due t o
involvement of t he vest ibular nuclei).
2. I psilat eral f acial hypalgesia and t hermoanest hesia, and corneal hypest hesia
(due t o involvement of t he t rigeminal spinal nucleus and t ract ). Facial
sensat ion is spared at t imes because of t he occasional occurrence of an
independent
vessel arising f rom t he basilar art ery supplying t he spinal t ract and nucleus
of t he t rigeminal nerve.
3. I psilat eral Horner syndrome (due t o int errupt ion of t he descending
pupilodilat or oculosympat het ic f ibers in t he lat eral port ion of t he pons and
medulla). O ccasionally, t here may also be a skew deviat ion[4] .
4. Cont ralat eral t runk and ext remit y hypalgesia and t hermoanest hesia w ere
not ed (due t o involvement of t he lat eral spinot halamic t ract ).
5. I psilat eral at axia and asynergia w ere not ed (due t o involvement of t he middle
cerebellar peduncle and cerebellum).
6. I psilat eral deaf ness and f acial paralysis w ere not ed (due t o involvement of
t he lat eral pont omedullary t egment um).
The clinical manif est at ions of an AI CA syndrome may at t imes be conf used w it h
t hose of t he lat eral medullary (Wallenberg) syndrome because of shared signs,
such as dysmet ria, vest ibular signs, Horner syndrome, and f acial sensory
impairment w it h cont ralat eral t runk and ext remit y pain, and t emperat ure sensory
loss[ 4] . How ever, f acial palsy and deaf ness due t o involvement of cranial nerves
VI I and VI I I and t heir nuclei, lat eral gaze palsy, and mult i-modal sensory
impairment of t he f ace should suggest an AI CA syndrome[4] .
AI CA t errit ory inf arct s may also present w it h isolat ed vest ibular manif est at ions
or isolat ed cerebellar signs [61, 68] . Tw o pat ient s have been described w it h
clinical f eat ures of inf arct ion in t he dist ribut ion of t he AI CA w ho had isolat ed
vert igo f or several mont hs bef ore inf arct ion[59] . Bot h pat ient s had
cerebrovascular risk f act ors and had experienced ot her episodes of t ransient
neurologic sympt oms not associat ed w it h vert igo. At t he t ime of inf arct ion, t hey
developed vert igo, unilat eral hearing loss, t innit us, f acial numbness, and
hemiat axia. MRI revealed ischemic lesions in t he lat eral aspect of t he pons and
middle cerebellar peduncle. Since t he blood supply t o t he inner ear and
vest ibulocochlear nerve arises f rom t he AI CA, t he vert igo preceding t he
inf arct ion may have result ed f rom t ransient ischemia t o t he inner ear st ruct ures
or t he vest ibular nerve[59] .
Dorsal Cerebellar Infarct (Superior Cerebellar Artery)

When t he superior cerebellar art ery (SupCA) is occluded at it s origin, pat ient s
may have ipsilat eral cerebellar signs, brainst em dist urbances, and a
cont ralat eral dissociat ed sensory syndrome. I n cont rast , w hen t here is an
occlusion of peripheral branches of t he SupCA, pat ient s of t en present only w it h
dysart hria and unst eady gait but w it hout vert igo, brainst em signs, or
cont ralat eral dissociat ed sensory dist urbances[84] . The “classic” present at ion of
SupCA t errit ory inf arct ion, as described by Mills, remains a rare occurrence [3,
6, 21, 41, 55, 56, 79, 81, 87] . When t he classic syndrome occurs, t he f ollow ing
may be f ound on examinat ion:
1. Vert igo and vomit ing (due t o involvement of t he vest ibular nuclei and
connect ions)
2. Nyst agmus (due t o involvement of t he medial longit udinal f asciculus and
cerebellar pat hw ays)
3. I psilat eral Horner syndrome (due t o compromise of t he descending
oculosympat het ic f ibers)
4. I psilat eral at axia and asynergia (due t o involvement of t he superior
cerebellar peduncle and cerebellum)
5. I psilat eral int ent ion t remor (due t o involvement of t he dent at e nucleus and
superior cerebellar peduncle)
6. Cont ralat eral t runk and ext remit y hypalgesia and t hermoanest hesia (due t o
involvement of t he lat eral spinot halamic and quint ot halamic t ract s)
7. Cont ralat eral hearing impairment (due t o involvement of t he crossed f ibers of
t he lat eral lemniscus)
8. Cont ralat eral f ourt h nerve palsy (due t o involvement of t he pont ine t ect um)
A SupCA dist ribut ion inf arct ion may also cause contrapul si on of saccadic eye
movement s associat ed w it h ipsilat eral limb at axia[64] . This saccadic disorder
has t hree element s: (a) horizont al saccades aw ay f rom t he lesion during
at t empt ed vert ical saccades, result ing in oblique t raject ories, (b) hypermet ria of
cont ralat eral saccades, and (c) hypomet ria of ipsilat eral saccades. This
cont rapulsion of saccades (lat eropulsion cont ralat eral t o a cerebellar lesion)
diff ers f rom t he lat eropulsion of saccades seen in t he lat eral medullary
syndrome, w hich is direct ed to the si de of t he lesion and associat ed w it h
hypermet ria of saccades toward t he brainst em lesion and hypomet ria of
saccades away f rom t he lesion (see Chapt er 15). Cont rapulsion of saccades has
also been described in associat ion w it h primary-posit ion upbeat nyst agmus in
cases of hemispheric cerebellar lesions[14] .
A st udy of 33 pat ient s w it h SupCA t errit ory inf arct ion[6] show ed f requent
associat ion w it h inf arct s in t he dist ribut ion of t he dist al basilar art ery
(73%), including t he rost ral brainst em, t halamosubt halamic region, and
occipit ot emporal lobes. Pat ient s present ed w it h alt ered level of consciousness,
ocular mot or abnormalit ies, signs of t halamic dysf unct ion, visual f ield def ect s,
cort ical blindness, and/ or memory loss[3] . O ne-t hird also had inf arct s in t he
dist ribut ion of t he PI CA, somet imes associat ed w it h inf arct s in t he dist ribut ion of
t he AI CA. Clinical present at ions included a rost ral basilar art ery syndrome; coma
at onset , of t en w it h t et raplegia; or cerebellar-vest ibular signs, of t en w it h
delayed coma due t o cerebellar sw elling. How ever, a “classic” SupCA syndrome
w as unusual [4, 6] .
I nf arct ion in t he dist ribut ion of t he lat eral branch of t he SupCA (anteri or rostral
cerebel l ar i nf arct) may present w it h ipsilat eral dysmet ria and axial lat eropulsion,
cont rapulsion of saccades, dysart hria, unst eadiness, and vomit ing [9, 64] . A
dysart hria–clumsy hand syndrome may also be t he present ing f eat ure[9] .
Pat ient s w it h ant erior rost ral cerebellar inf arct ion usually improve w it hout
suff ering major sequelae. Dysart hria is f requent ly seen w it h t he involvement of
t he t errit ory of t he medial branch of t he SupCA [4, 46] . Select ive involvement of
t he ant erior cerebellar lobe in cases of medial SupCA t errit ory inf arct ion may
cause mild appendicular dysmet ria and spont aneous ext ensor post uring of t he
neck, t runk, and all f our ext remit ies[66] .
Pat ient s w it h inf arct s in t he t errit ories of t he PI CA or t he SupCA w ere st udied t o
compare t heir clinical present at ions, course, and prognosis[40] . I n 36 pat ient s
w it h PI CA t errit ory inf arct s, a t riad of vert igo, headache, and gait imbalance
predominat ed at st roke onset , and comput ed t omography show ed signs of
severe cerebellar mass eff ect (30%) w it h associat ed hydrocephalus and
brainst em compression, result ing in f our deat hs. I n 30 pat ient s w it h SupCA
inf arct s, gait dist urbances predominat ed at onset ; vert igo and headache w ere
signif icant ly less common. The clinical course w as usually benign, and comput ed
t omography show ed signs of cerebellar mass eff ect , hydrocephalus, and
brainst em compression in only 7% of t he cases. Presumed cardiac embolism or
art ery-t o-art ery embolism w as t he predominant st roke mechanism in pat ient s
w it h SupCA dist ribut ion inf arct s, w hereas in t hose w it h PI CA dist ribut ion inf arct s,
t he st roke mechanism w as equally divided bet w een t hose w it h cardiac sources
of embolism and t hose w it h post erior circulat ion at herot hrombot ic occlusive
disease. Thus, cerebellar inf arct s in t he PI CA and SupCA dist ribut ion have
dist inct diff erences in clinical present at ion, course, and prognosis[40] .
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> Table of C ontents > C hapter 17 - The Loc aliz ation of Les ions Affec ting the Hypothalam us and
P ituitar y Gland
Chapter 17
The Localization of Lesions Affecting the
Hypothalamus and Pituitary Gland
Anatomy of the Region

The hypot halamus const it ut es t he lat eral w all of t he t hird vent ricle [25, 44] . I t is
separat ed f rom t he t halamus by t he hypot halamic sulcus. The t w o w alls of t he
t hird vent ricle merge ant eriorly t o f orm t he lamina t erminalis, relat ed superiorly
t o t he ant erior commissure and inf eriorly t o t he opt ic chiasm[20] .
Lat eropost eriorly, t he hypot halamus borders on t he globus pallidus, int ernal
capsule, subt halamic region, and crus cerebri. An inf erior prolongat ion of t he
f loor of t he t hird vent ricle, t he pit uit ary st alk or inf undibulum, joins t he
hypot halamus w it h t he pit uit ary gland or hypophysis. Each pillar of t he f ornix,
descending rost rocaudally t o end in t he mammillary body, divides t he
hypot halamus int o a medial and a lat eral region.
Main Hypothalamic Nuclear Groups

The hypot halamic nuclei can be concept ualized by considering t he hypot halamus
as divided by (a) a coronal plane t hrough t he inf undibular st alk and (b) an angled
parasagit t al plane cont aining t he f ornix. These planes separat e f our regions:
ant erior, post erior, medial, and lat eral. The t opography of t he hypot halamic
nuclei is illust rat ed in Figure 17-1 and Figure 17-2.
Connections of the Hypothalamus

The origin, pat hw ays, and t erminat ion of t he main aff erent and eff erent
hypot halamic connect ions are list ed in Table 17-1. I n summary, t he hypot halamus
has st rong t o and f ro connect ions w it h (a) t he midbrain and post erior t egment um,
w hich play an import ant role in alert ness; (b) t he limbic syst em, t hrough t he
mesial t emporal cort ex, ant eromedial t halamic region, and amygdala, w hich play
an import ant role in emot ion and memory[119] , and (c) t he “aut onomic” nuclei of
t he brainst em and spinal cord, such as t he dorsal nucleus of t he vagus and t he
nucleus t ract us solit arius. Alt hough direct connect ions have been t raced t o t he
ipsilat eral int ermediolat eral cell column of t he spinal cord, much of t he inf luence
of t he hypot halamus on t he aut onomic cent ers of t he cord is probably exert ed
t hrough t he brainst em ret icular f ormat ion[25] . Pat hw ays f rom t he ret ina and
olf act ory syst em convey t o t he hypot halamus inf ormat ion needed f or t he
circadian cont rol of veget at ive f unct ions, and f or f eeding and reproduct ive
behavior[ 113] .
Much w ork remains t o be done t o def ine t he localizat ion and f unct ion of t he many
put at ive neurot ransmit t ers ident if ied in t he hypot halamus[18] . Mult iple
neuropept ides have been ident if ied in t he hypot halamus of experiment al animals
and humans [47, 58, 86, 98] . I n addit ion t o t he hypophysiot ropic hormones
regulat ing ant erior pit uit ary secret ion, ot her neuropept ides play a role in t he
regulat ion of body t emperat ure (bombesin, neurot ensin), alert ness (orexin,
somat ost at in), cardiopulmonary f unct ion (t hyrot ropin-releasing hormone,
calcit onin gene-relat ed pept ide), w at er balance (enkephalins), circadian rhyt hms
(neuropept ide Y ), f eeding behavior (cholecyst okinin, bombesin, galanin, lept in,
neuropept ide Y ), and reproduct ive f unct ion (oxyt ocin, vasoact ive int est inal
pept ide). How ever, t he complex hypot halamic act ions of t hese pept ides and
ot hers present in high concent rat ion in t he hypot halamus (e. g. , subst ance P,
mot ilin, secret in) need t o be clarif ied f urt her[86] . Hypot halamic st eroids play an
import ant role in t he sexual diff erent iat ion of hypot halamic nuclei and in
reproduct ive behavior [18] . Among t he biogenic aminergic pat hw ays, t he best
know n is
t he t uberoinf undibular dopamine syst em arising in t he arcuat e nucleus and

project ing t o t he median eminence. Dopamine in t he port al syst em inhibit s t he
release of prolact in[98] . Noradrenergic t erminals, originat ing in t he nucleus locus
coeruleus and t he lat eral ret icular nucleus of t he medulla, are f ound mainly in t he
paravent ricular and ret rochiasmat ic areas, and in t he vent romedial and
dorsomedial nuclei. Serot oninergic pat hw ays f rom t he raphe nuclei reach t he
suprachiasmat ic nucleus, suggest ing a role f or serot onin in t he regulat ion of
circadian rhyt hms. Regarding ot her neurot ransmit t ers, a cholinergic
t uberoinf undibular pat hw ay has been described [95, 123] .
FI G URE 17-1 Schemat ic diagram of t he hypot halamic nuclei
FI G URE 17-2 Hypot halamic nuclei

TABLE 17-1 Connections of the Human Hypothalamu
Term ination
Origin Tract
Neurotransm
Afferent hypothalamic connections
Medial
Fornix Mammillary bo
temporal cortex
Midbrain
Mammillary peduncle Mammillary bo
tegmental nuclei
Ventromedial
Amygdala Stria terminalis nucleus
Arcuate nucle
Posterior nucl
Periaqueductal Suprachiasma
Dorsal longitudinal
gray nucleus
fasciculus
Raphe nuclei Median emine
(serotonin)
Paraventricula
nucleus
Dorsomedial
Nucleus locus
nucleus
coeruleus
Ventromedial
nucleus
(noradrenaline
Paraventricula
Nucleus nucleus

tractus solitarius Dorsomedial
nucleus
Arcuate nucle
Retina, Suprachiasma
Geniculohypothalamic
pregeniculate nucleus
tract
nucleus Arcuate nucle
Olfactory
Medial forebrain bundle Lateral area
nerve
Medial forebrain
Septal nuclei Mammillary bo
bundle, fornix
Dorsomedial
Lateral area
thalamic nucleus
Orbitofrontal
Lateral area
cortex
Efferent hypothalamic connections
Paraventricular Neurohypophy
nucleus, (oxytocin,
Supraopticohypophysial
supraoptic antidiuretic
nucleus hormone)
Hypophysial p
system
Arcuate
Tuberoinfundibular (hypophysiotr
nucleus
hormones,
dopamine)
Mammillary Anterior thala
Mammillothalamic
body nucleus
Mammillary Dorsal and ve

Mammillotegmental
body tegmental nuc
Lateral area Medial forebrain bundle Septum
Dorsal longitudinal Periaqueducta

Medial nuclei
fasciculus gray
Raphe nuclei
Ventromedial
Nucleus locus
nucleus
coeruleus
Dorsal nucleu
the vagus
Nucleus ambi
Several pathways Nucleus tractu
Several nuclei
(uncrossed) solitarius
Intermediolate
cell column of
spinal cord
a Anatomically larger connections are listed first.

b Neurotransmitters for many pathways remain unidentified.
FI G URE 17-3 Hypot halamic-pit uit ary connect ions
Hypot halamic cont rol of veget at ive f unct ions is exert ed t o a great ext ent t hrough
t he pit uit ary gland. The hormonal secret ions of t he ant erior pit uit ary are
regulat ed by t he hypot halamic-releasing f act ors or hypophysiot ropic hormones,
w hich are released int o t he inf undibular port al syst em (Fig. 17-3). Through t his
syst em, t he ant erior pit uit ary receives t he richest blood f low of any organ in t he
body, 0. 8 mL/ g/ minut e[100] . The inf undibulum also cont ains t he import ant
supraopt ic-hypophysial t ract , const it ut ed by axons f rom neurons in t he
supraopt ic and paravent ricular nuclei. Those axons end in a rich capillary
net w ork in t he post erior lobe of t he pit uit ary (neurohypophysis), w here t hey
secret e oxyt ocin and Ant idiuret ic Hormone ADH; also called vasopressi n).
Clinical M anifestations of Hypothalamic or Pituitary

Dysfunction
Bef ore discussing t he most likely locat ion of a lesion causing such sympt oms or
signs as are at t ribut able t o t he hypot halamic-pit uit ary region (Table 17-2),
several point s should be not ed.
1. Since t hese st ruct ures are small, several port ions may be involved
simult aneously. For t his reason, t he f ine localizat ion of f unct ions t o specif ic
hypot halamic st ruct ures is of t en not know n f rom human lesions and has t o be
ext rapolat ed f rom experiment al animal dat a[117] .
2. Lesions t hat progress rapidly cause a more f lorid clinical sympt omat ology
t han t hose t hat proceed slow ly. For inst ance, a surgical or vascular lesion in
t he post erior hypot halamus renders t he pat ient comat ose, w hereas a slow ly
grow ing t umor aff ect ing t he same st ruct ures causes only apat hy.
3. Unilat eral lesions are seldom sympt omat ic.
4. The changes of hypot halamic f unct ion w it h age are ref lect ed in t he disparit y
of t he syndromes caused in diff erent age-groups by similarly locat ed
lesions[ 104] . For inst ance, a similar lesion may cause dw arf ism during
childhood and gigant ism during adult hood[36] .
Disturbances of Temperature Regulation

The hypot halamic “t hermost at ” f or normal t emperat ure regulat ion is locat ed in
t he ant erior-preopt ic hypot halamic area, w hose neurons alt er t heir f iring rat e in
response t o a w arm or cold environment [19] . How ever, t he physiologic
responses f or heat ing (e. g. , vasoconst rict ion, shivering, increased
f ood int ake) and cooling (e. g. , increased sw eat ing, peripheral vasodilat ion,
pant ing, decreased mot or behavior) are cont rolled by mechanisms locat ed in or
t raversing t he post erior hypot halamus. Because heat dissipat ion is normally
needed in a w arm ambient t emperat ure, hypert hermia result s f rom ant erior
hypot halamic lesions, w hereas post erior lesions cause hypot hermia or
poikilot hermia by int erf ering w it h heat -conservat ion responses [86, 104] . Several
neurot ransmit t ers and neuropept ides delivered int o t he hypot halamus of
experiment al animals have been show n t o induce t emperat ure changes. For
inst ance, serot onin and low doses of opioids induce hypert hermia, w hereas high
doses of opioids, angiot ensin 11, dopamine, acet ylcholine, somat ost at in, and
neurot ensin cause hypot hermia [86, 96] . Their role in t emperat ure regulat ion in
humans needs t o be clarif ied f urt her.
TABLE 17-2 Clinical M anifestations of Hypothalamic

or Pituitary Dysfunction
Disturbances of temperature regulation

Hypothermia
Hyperthermia
Poikilothermia
Disturbances of alertness and sleep
Hypersomnia
Narcolepsy
Insomnia
Circadian abnormalities
Autonomic disturbances
Cardiac
Pulmonary
Gastrointestinal
“Diencephalic epilepsy”
Anhydrosis
Disturbances of water balance
Diabetes insipidus
Essential hypernatremia
Inappropriate secretion of antidiuretic hormone
Reset osmostat hyponatremia
Primary hyperdipsia
Disturbances of caloric balance
Obesity
Emaciation
Disturbances of reproductive functions
Hypogonadotropic hypogonadism
Nonpuerperal galactorrhea
Precocious puberty
Uncontrollable sexual behavior
Other endocrine disturbances
Disturbances of memory
Disturbances of emotional behavior and affect
Rage and fear
Apathy and chronic fatigue
Depression
Gelastic seizures
Headache
Episodic headaches
Impaired visual acuity, field defects
Diplopia, pupillary changes
Physiologic Rhythms
Diurnal Variation
Body t emperat ure peaks early in t he evening and reaches t he low est point early
in t he morning[86] . Lesions in t he median eminence may f lat t en t he diurnal
t emperat ure variat ion[115] .
Menstrual Cycle
Body t emperat ure increases at t he t ime of ovulat ion; progest erone produces t his
eff ect by act ing on hypot halamic neurons.
Hypothermia
Chronic
Most of t en t he lesion involves t he post erior or t he ent ire hypot halamus. When
discomf ort is also present , t he lesion may be in t he ant erior hypot halamus. The
most common causes include Wernicke's encephalopat hy[131] , head t rauma,
craniopharyngioma, glioblast oma mult if orme, surgery, hydrocephalus, inf arct ion,
and sarcoidosis[86] .
Paroxysmal
Spontaneous peri odi c hypothermi a; “di encephal i c epi l epsy. ” This is a rare
syndrome charact erized by an episodic decrease of body t emperat ure [71, 80,
94] . The onset is abrupt , w it h sw eat ing and vasodilat at ion leading t o hypot hermia
(as low as 30°C rect ally), accompanied by nausea, vomit ing, hypot ension,
bradycardia, cardiac arrhyt hmias, salivat ion, lacrimat ion, at axia, ast erixis, and
ment al dullness. The episodes last f rom minut es t o hours; t hey may recur only
af t er decades or t hey may recur more of t en, even daily. Thermoregulat ion may
be
normal bet w een at t acks[80] . Lesions responsible f or t his condit ion have involved
t he arcuat e nucleus and premammillary area. A similar syndrome appeared af t er
surgery f or a midbrain glioma[48] . This hypot halamic dist urbance is of t en
associat ed w it h agenesis of t he corpus callosum (Shapiro syndrome)[ 99] . O ne
pat ient had alt ered norepinephrine met abolism and responded t o clonidine
t herapy[ 111] . O t her pat ient s responded t o bromocript ine and morphine[26] .
Hyperthermia
Pyrogen Induced
This is t he most common cause of hypert hermia. Cases clinically labeled as
hypothal ami c hyperthermi a af t er an unrevealing search f or an inf ect ious source
of t en belong t o t his cat egory. Bact erial or viral pyrogenes can direct ly st imulat e
t he hypot halamus and in addit ion induce t he release of int erleukin 1 (endogenous
pyrogen) f rom leukocyt es and macrophages[37] . Circulat ing int erleukin 1 act s in
t he preopt ic and paravent ricular area of t he ant erior hypot halamus, inducing
prost aglandin E2 synt hesis, w hich can be blocked by aspirin [7, 86, 118] .
Acute Hyperthermia
Acut e hypert hermia may occur as a consequence of an acut e process
(craniot omy, t rauma, bleeding), and last f or less t han 2 w eeks. The lesion
aff ect s t he ant erior hypot halamus. Cardiovascular changes, normally present
w it h f ever, are disproport ionat ely small w it h hypert hermia due t o hypot halamic
lesions[ 104] .
Paroxysmal Hyperthermia
I nvolvement of t he vent romedial hypot halamus has been suspect ed in t hese rare
cases, alt hough t he precise localizat ion is not know n [86, 127] . O ne pat ient
improved af t er phenyt oin administ rat ion. Anot her pat ient responded t o
chlorpromazine. This boy had recurrent episodes of f ever, hypert ension, w eight
loss, and vomit ing, last ing f or about 3 days[104] . A pat ient w it h agenesis of t he
corpus callosum and periodic hypert hermia became hypot hermic af t er dopamine
administ rat ion[ 60] .
Malignant Hyperthermia
This syndrome is discussed here w it h ot her abnormalit ies of t emperat ure cont rol
alt hough it is not caused by hypot halamic dysf unct ion. When exposed t o various
anest het ic agent s and ot her drugs, suscept ible individuals may develop a
pot ent ially f at al st at e of severe generalized muscular rigidit y, met abolic acidosis,
myoglobinuria, and hypert hermia [53, 97] . Hypert hermia is t hought t o be due t o
an int rinsic abnormalit y of t he excit at ion—cont ract ion-coupling mechanism in
skelet al muscle, induced by drug exposure, result ing in sust ained myof ibrillar
cont ract ion. Suscept ibilit y t o t his syndrome is t ransmit t ed as an aut osomal
dominant t rait and in some cases calcium channels are abnormal[52] .
Neuroleptic Malignant Syndrome

This syndrome is a pot ent ially lif e-t hreat ening idiosyncrat ic react ion t o
neurolept ic drugs [34, 59] . The clinical t riad consist s of : (a) hypert hermia,
usually w it h ot her aut onomic dysf unct ions such as t achycardia, f alls in blood
pressure, and diaphoresis, (b) ext rapyramidal signs, usually increased muscle
t one (rigidit y) w it h dyst onia, of t en accompanied by elevat ed creat inine kinase,
and (c) alt ered ment al st at us, such as inat t ent ion, agit at ion, and conf usion.
Clinical manif est at ions usually occur abrupt ly at t herapeut ic levels of
neurolept ics, w it h all of t he sympt oms f ully manif est w it hin 24 hours and reaching
a maximum w it hin 72 hours. This syndrome, w hich has also been described
f ollow ing t he abrupt w it hdraw al of levodopa [43, 70] , can be f at al in up t o 20%
t o 30% of cases. A syndrome w it h milder f ever and a great er t endency t o
develop myoclonus has been described w it h t he use of serot onin reupt ake
inhibit ors[ 27] .
Poikilothermia
Poikilot hermia is t he f luct uat ion of more t han 2°C in body t emperat ure f ollow ing
ambient t emperat ure [2] . I t is t he most common cent ral neurogenic abnormalit y
of heat regulat ion in humans. Such pat ient s are unaw are of t heir condit ion and
show no sign of discomf ort or behavioral regulat ion w it h t hermal st ress.
Poikilot hermia result s f rom post erior hypot halamic lesions[104] .
Disturbances of Alertness and Sleep

Larger lesions involve t he rost rovent ral component s of t he ascending ret icular
act ivat ing syst em. Smaller lesions may cause more localized dysf unct ion of
st ruct ures regulat ing sleep, part icularly t he suprachiasmat ic nucleus, w hich plays
a major role in t he regulat ion of circadian cycles, or t he hypocret in/ orexin
nucleus in t he post erolat eral hypot halamus [9, 92] . The suprachiasmat ic nucleus,
locat ed in t he ant erior hypot halamus, receives aff erent s f rom t he ret ina and
possibly f rom t he lat eral geniculat e body and mainly project s not only t o ot her
hypot halamic nuclei, but also t o t he basal f orebrain, t halamus, and
periaqueduct al gray[113] . Circadian rhyt hms are import ant f or most hypot halamic
f unct ions. For inst ance, oxyt ocin, w hich plays a major role in sexual behavior, is
secret ed mainly in t he early hours of t he night [42] .
Coma, Hypersomnia, or Akinetic M utism

These are occasionally relat ed t o post erior hypot halamic or larger lesions[112] .
The most common report ed causes have been t umors and Wernicke's
encephalopat hy [108, 131] . A pat ient w it h ext reme akinesia af t er removal of a
hypot halamic epidermoid cyst improved w it h dopamine recept or agonist s[109] .
Hypersomnia and coma result f rom midbrain lesions more of t en t han f rom
hypot halamic lesions.
Narcolepsy
I n t he perif ornical area of t he post erolat eral hypot halamus t here is a clust er of
cells t hat secret e hypocret in or orexin, a pept ide t hat mediat es w akef ulness and
f acilit at es f eeding behavior [9, 92] . A lack of t his subst ance causes narcolepsy.
G iven t he similar human leukocyt e ant igen (HLA) t ype of t he pat ient s, it is
speculat ed t hat t he damage of t hese cells is of an aut oimmune nat ure [9, 92] .
Insomnia
Few er t han 10 cases t hat implicat e t he ant erior hypot halamus have been
report ed[ 104] . How ever, some insomniacs may have increased product ion of
st ress-relat ed hormones[130] .
Circadian Abnormalities
Loss of neurons in t he suprachiasmat ic nucleus occurs in Alzheimer's disease,
at t ended by phase advance and reduced period and amplit ude of t he sleep
cycles, as w ell as increased variabilit y and decreased st abilit y of t he rhyt hm[93] .
Loss of circadian rhyt hmicit y has also been described w it h lesions in t he region
of t he suprachiasmat ic nucleus, including opt ic glioma [32, 95] .
Sympat het ic areas t end t o be vent romedial and post erior. St imulat ion of t hese
areas causes hypert ension, pupillary dilat ion, t achycardia, vasoconst rict ion of
vascular beds, vasodilat ion of muscular beds, and increased cardiac cont ract ilit y
in associat ion w it h t he expression of rage or f ear[112] .
Parasympat het ic areas t end t o be paravent ricular or lat eral, and ant erior.
St imulat ion of t hese areas causes pupillary const rict ion. St imulat ion of t he
ant erior parasympat het ic areas causes hypot ension and bradycardia, w hereas
st imulat ion of t he post erior parasympat het ic areas causes only increased blood
f low t hrough t he bow el and decreased blood f low in t he skelet al muscle[104] .
Alt hough t he hypot halamus seems t o cont ribut e t o t he cont rol of mict urit ion in
humans, urinary incont inence is not described as a sympt om of isolat ed
hypot halamic damage[17] .
Cardiac M anifestations
Hypert ension, cardiac arrhyt hmias, Elect rocardiogram (ECG ) abnormalit ies
simulat ing myocardial inf arct ion, or even myocardial inf arct ion in a nonvascular
pat t ern may f ollow subarachnoid or int ravent ricular hemorrhages, part icularly
t hose due t o rupt ured ant erior communicat ing art ery aneurysm[124] . The cardiac
damage is mediat ed by an out pouring of cat echolamines[83] . Chronic heart
f ailure w it h chronic st ress may be mediat ed by t he paravent ricular nucleus[12] .
Respiratory Abnormalities
Pulmonary edema and hemorrhage can result f rom acut e hypot halamic damage
(hemorrhage, head t rauma). Sudden dysf unct ion of t he parasympat het ic region in
t he ant erior hypot halamus, w it h consequent hypert ension, lef t heart st rain, and
loss of pulmonary surf act ant , may explain t he clinical pict ure [86, 104] .
Gastrointestinal Abnormalities
Acut e hypot halamic lesions (t rauma, encephalit is, acut e mult iple sclerosis,
hemorrhage, inf arct ion, abscess, meningit is) can cause gast roint est inal
ulcerat ion. Neurogenic ulcers are most of t en locat ed in t he low er esophagus,
ot herw ise an uncommon sit e f or ulcerat ion. Neurogenic ulcers may be caused by
acut e lesions anyw here in t he neuraxis, f rom t he ant erior hypot halamic region t o
t he dorsal nucleus of t he vagus or even in t he spinal cord. Alt hough t he
hypot halamus is act ivat ed during emesis, t here is no evidence t hat hypot halamic
damage alt ers t he emet ic ref lex[62] . Emesis is a prominent f eat ure of t he
epilept ic syndrome in children called Autonomi c sei zures and autonomi c status
epi l epti cus or Panayi otopoul os syndrome[ 101] . I n a t ypical present at ion, t he
child, f ully conscious, able t o speak and underst and, complains “I f eel sick, ”
looks pale, and vomit s. O t her aut onomic sympt oms may f ollow, as w ell as a
generalized seizure. Alt hough t he Elect roencephalogram (EEG ) of t en show s
occipit al spikes, Panayiot opoulos is of t he opinion t hat t he hypot halamus is
involved in t he genesis of t his syndrome[101] .
Diencephalic Epilepsy
Diencephalic epilepsy ref ers t o episodes of hypert ension, t achycardia, f lushing,
salivat ion, sw eat ing, and oscillat ions in t emperat ure w it h preserved alert ness,
but w it h t he behavioral and aff ect ive responses appropriat e t o t he alt ered
aut onomic response[104] . The EEG , w hich may be abnormal
in half t he cases, show s slow ing but seldom t he paroxysmal dysrhyt hmias
charact erist ic of most f orms of epilepsy. Approximat ely half t he pat ient s have
responded t o ant iconvulsant s. Alt hough aut onomic dist urbances are common in
many t ypes of seizures, t he clinical pict ure described in t he preceding t ext has
been f ound w it h t hird vent ricular t umors or t hird vent ricular dilat ion caused by
hydrocephalus [86, 104] .
Unilateral Anhidrosis or Hyperhidrosis

Unilat eral hypot halamic lesions may cause ipsilat eral anhidrosis of t he body,
w hich is generally incomplet e. An ipsilat eral Horner syndrome is of t en present in
t hese cases. Dysf unct ion of t he sympat het ic cent ers in t he post erior
hypot halamus may be responsible f or t hese f indings. Transient hyperhidrosis
cont ralat eral t o large cerebral inf arct s has also been described[75] . No
associat ed aut onomic dysf unct ion w as present . I n at least one of t hese cases
t he ipsilat eral pupil w as smaller and t he pat ient w as f ebrile, raising t he
possibilit y t hat t he f inding may act ually represent relat ive anhidrosis on t he side
ipsilat eral t o t he inf arct . G eneral i zed or segment al hypo- or anhidrosis may be
seen w it h cent ral nervous syst em condit ions such as Shy-Drager syndrome
(mult isyst em at rophy w it h aut onomic f ailure), Parkinson's disease, mult iple
sclerosis, spinal cord disease, st roke, or t halamot omy[29] .
Disturbances of Water Balance

Hypot halamic osmorecept ors are in t he supraopt ic and paravent ricular nuclei or
t heir proximit y. I t has been post ulat ed t hat int racellular dehydrat ion, manif est ed
by increased int racellular sodium concent rat ion, or ext racellular dehydrat ion,
manif est ed by increased angiot ensin I I concent rat ion in t he hypot halamic blood,
st imulat e t hese osmorecept ors, w hich in t urn elicit t he release of ADH by t he
large cells of t he supraopt ic and paravent ricular nuclei. By cont rast , w hen t he
int ravascular volume increases, peripheral volume recept ors in t he large veins
and lef t at rium mediat e inhibit ion of ADH secret ion[104] .
The lat eral hypot halamus, classically considered t he drinking cent er, cont ains
osmorecept ors but may also inf luence drinking behavior by causing general
excit abilit y of t he region. I n experiment al animals, dest ruct ive lesions of t he
lat eral hypot halamus cause adipsia (reduced w at er int ake), but not enough t o
result in dehydrat ion. By cont rast , dest ruct ive lesions of t he vent romedial nuclei
may cause hyperdipsia.
Diabetes Insipidus (Decreased Antidiuretic Hormone

Release but Normal Thirst)
Alt hough lack of ADH prevent s w at er reabsorpt ion in t he dist al t ubule, w it h
consequent excret ion of a large volume of dilut e urine, an int act t hirst mechanism
induces w at er int ake, t hereby prevent ing hypernat remia. Diabet es insipidus [86,
104] result s f rom t he dest ruct ion of at least 90% of t he large neurons in t he
supraopt ic and paravent ricular nuclei. Except f or t he f amilial variet y, t he lesion
of t en involves t he supraopt ic-hypophysial t ract rat her t han t he neuronal bodies
t hemselves. I n such cases, t he disorder is of t en t ransient .
Diabet es insipidus may be f amilial, linked in some f amilies t o a mut at ion in t he
vasopressin region of chromosome 20 [69, 106] , or caused by granulomas
(sarcoidosis, meningovascular syphilis, hist iocyt osis), vascular lesions, t rauma,
meningoencephalit is, or aut oimmune damage t o vasopressin-producing cells [84,
114] . Anxiet y, alcohol, phenyt oin, and ant icholinergic agent s reduce t he secret ion
of ADH.
Essential Hypernatremia (Decreased Antidiuretic

Hormone Release w ith Absence of Thirst)
Diagnosis of t his rare syndrome requires (a) hypernat remia unaccompanied by a
corresponding f luid def iciency, (b) preserved renal responsiveness t o ADH, (c)
impaired secret ion of ADH w it h hypernat remia, and (d) absence of t hirst despit e
preserved conscious behavior [3, 54, 86, 104] . Some pat ient s w it h t he syndrome
have a remarkable t olerance t o hypernat remia, t o t he point of developing w at er
int oxicat ion w hen t he condit ion is t reat ed. Sodium levels reaching 170 mEq per
lit er, how ever, are at t ended by muscle cramping, t enderness and w eakness,
f ever, anorexia, paranoia, and let hargy. Lesions causing t his syndrome have
aff ect ed t he t uberal region or t he ent ire hypot halamus[41] . The regulat ion of
at rial nat riuret ic pept ide may be abnormal in some pat ient s w it h a similar
met abolic derangement [65] . O t her pat ient s have excessive renal responsiveness
t o ADH[39] .
Inappropriate Secretion of Antidiuretic Hormone

(Elevated Antidiuretic Hormone Release w ith Normal
Thirst)
I nappropriat e secret ion of ant idiuret ic hormone (SI ADH) [86, 104] is
charact erized by (a) serum hyposmolarit y (<280 mO sm/ kg) and hyponat remia
(<130 mEq/ L), (b) normal renal excret ion of sodium, and (c) inappropriat ely high
urine osmolalit y
w it hout body f luid deplet ion. Renal and adrenal f unct ions are normal. Serum
levels of ADH are elevat ed. The pat ient has anorexia, nausea, vomit ing, and
irrit abilit y t hat may progress t o paranoid delusions and generalized seizures
w hen t he serum sodium f alls below 110 mEq per lit er. Alt hough SI ADH is more
of t en due t o ext rahypot halamic causes, part ial damage of t he supraopt ic and
paravent ricular nuclei or neighboring areas may cause t he syndrome. Such
damage may be due t o t rauma, subarachnoid hemorrhage, hydrocephalus,
t umors, meningit is, encephalit is, or drugs, part icularly vincrist ine,
chlorpropamide, cyclophosphamide, carbamazepine, and chlorpromazine.
Product ion of ADH by a t umor (e. g. , carcinoma of t he lung) or inf lammat ory
t issue out side t he hypot halamus may also cause t he syndrome, w hich has also
been linked t o myxedema, cardiac f ailure, nonneoplast ic pulmonary disease, and
t o porphyria and ot her peripheral neuropat hies. I mpairment of peripheral aff erent
inhibit ory pat hw ays carrying inf ormat ion f rom t he volume recept ors t o t he
hypot halamus has been invoked t o explain SI ADH w it h polyneuropat hies[104] .
O f t en hyponat remia w it h hypot halamic-pit uit ary disease is due t o polydipsia w it h
normal ADH levels[121] .
Reset Osmostat Hyponatremia

Crit eria f or t his diagnosis[6] include normovolemic hypot onic hyponat remia;
normal renal, adrenal, and t hyroid f unct ion; abilit y t o concent rat e t he urine w hen
serum t onicit y is raised above t he reset level of serum osmolalit y; abilit y t o
excret e a w at er load; and maint enance of normal sodium balance w it hout
correct ion of hyponat remia during salt loading.
Primary Polydipsia or Hyperdipsia (Excessive Water

Drinking in the Absence of Hypovolemia or
Hypernatremia)
Pat ient s w it h t his dist urbance[104] may drink in response t o (a) condit ioned
behavior (“beer drinker's hyponat remia”, “t ea part y epilepsy”) or ot her
psychogenic f act ors, (b) hyperangiot ensinemia, f ound in renal pat ient s w it h t hirst
despit e a normal elect rolyt e balance maint ained w it h hemodialysis, or (c) rarely,
hypot halamic disease. I n t he last case, drinking of t en compensat es f or mild
diabet es insipidus.
Disturbances of Caloric Balance and Feeding Behavior

The hypot halamus part icipat es in f eeding behavior t hrough caref ully t uned
mechanisms [8, 24] . For inst ance, neurons in t he arcuat e and paravent ricular
nuclei are rich in Amp-Act ivat ed Prot ein Kinase (AMPK), a sensor of t he cellular
AMP: ATP rat io and t heref ore a gauge of cellular met abolism[66] . Feeding,
hyperglycemia, and t he anorexigenic hormones insulin and lept in decrease AMPK
act ivit y in hypot halamic nuclei. Conversely, f ast ing, hypoglycemia, and t he
st omach-derived orexigenic hormone, ghrelin, increase hypot halamic AMPK,
t hereby st imulat ing f eeding behavior.
Alt hough dist urbances of f eeding behavior are not uncommon w it h hypot halamic
lesions, t hey have been report ed also w it h f ront al or t emporal lesions,
part icularly in t he right hemisphere[126] .
Obesity
Lesions in t he vent romedial port ion of t he hypot halamus may cause obesit y[10] .
Charact erist ically, such pat ient s are hyperphagic (bulimic) unt il a higher body
w eight is reached, at w hich point t hey maint ain a st able body w eight unless t he
lesion progresses. The f eeding behavior of pat ient s w it h hypot halamic lesions
resembles t hat of obese individuals w it h no demonst rable lesions. Compared t o
normal individuals, pat ient s w it h hypot halamic lesions (a) eat only a slight excess
of f ood each day, (b) are less act ive, (c) eat f ew er meals each day, (d) eat
more at each meal, (e) eat more quickly, (f ) eat more of f ood t hat t ast es good,
(g) eat more w hen f ood is easily accessible, and (h) react more emot ionally and
are appeased by f ood int ake[86] . O besit y af t er vent romedial lesions may result
f rom aff ect ion of t he cat echolaminergic pat hw ays coursing in t his region, rat her
t han f rom dest ruct ion of t he nuclei t hemselves. Most f requent lesions include
craniopharyngioma, pit uit ary adenoma, surgery f or t he removal of t hese t umors,
ot her t ypes of t rauma, encephalit is, and vascular lesions of t he base of t he brain
[ 21, 56] . Compulsive eat ing may be caused by rat her nonspecif ic brain lesions.
O ccasionally, it may respond t o ant iconvulsant t herapy[51] . I mpaired secret ion of
cholecyst okinin has been described in bulimia nervosa[46] . Hypot halamic
serot oninergic st imulat ion reduces f ood int ake, part icularly of carbohydrat es,
and increases energy expendit ure, t hus reducing w eight [77] . The f ollow ing
obesit y syndromes are t hought t o be due t o hypot halamic dysf unct ion.
Kleine-Levin Syndrome
Kleine-Levin syndrome is a rare variet y of compulsive eat ing behavior in
adolescent males, charact erized by episodes of hyperphagia, w it h or w it hout
excess appet it e, periodic hypersomnolence, hyperact ivit y w hen aw ake, and
behavioral dist urbances, part icularly, hypersexualit y and exhibit ionism. Alt hough
t radit ionally considered a hypot halamic
derangement , medial t halamic pat hology w as report ed in one case[28] and

hypopigment at ion of t he subst ant ia nigra and locus coeruleus in anot her[72] . A
viral illness preceded t he onset of t he syndrome in some cases. The disorder
usually disappears during t he t hird decade. Endocrinological evaluat ion has
f ailed t o show abnormalit ies during t he periods of abnormal behavior[88] .
Prader-Willi Syndrome
Prader-Willi syndrome comprises obesit y, hypogenit alism, ment al ret ardat ion,
short st at ure, micromelia, and a t endency t o develop diabet es mellit us[61] .
Aff ect ed inf ant s t end t o be hypot onic (neonat al hypot onia), somnolent , and eat
lit t le, but bet w een 6 mont hs and 2 years of age t hey begin t o eat in excess and
become obese. Abnormal lut einizing hormone-releasing hormone neurons are
t hought t o be responsible f or t he decreased levels of sex hormones, result ing in
non-descended t est es, undersized sex organs, and insuff icient grow t h during
pubert y. A lack of grow t h hormone–releasing hormone may also cont ribut e t o t he
short st at ure of pat ient s w it h Prader-Willi syndrome[35] . I n addit ion, t he
aberrant cont rol of body t emperat ure and dayt ime hypersomnolence may result
f rom hypot halamic dist urbances. The number of oxyt ocin neurons—t he put at ive
sat iet y neurons— in t he hypot halamic paravent ricular nucleus is markedly
decreased in Prader-Willi syndrome. This is presumed t o be t he basis of t he
insat iable hunger and obesit y of pat ient s w it h t he syndrome[81] . I t is caused by
a lack of pat ernal genet ic inf ormat ion at 15q11-q13, due t o impaired pat ernal
imprint ing of several genes[49] .
Laurence-Moon-Bardet-Biedl Syndrome
Laurence-Moon-Bardet -Biedl syndrome comprises obesit y, hypogonadism,
ment al def iciency, ret init is pigment osa, and polydact yly [50, 86] . Diabet es
insipidus and renal f ailure are of t en present . The condit ion is t ransmit t ed as an
aut osomal recessive t rait , genet ically het erogenous, w it h at least f our loci
locat ed t o dat e. I n most f amilies t he def ect is linked t o 11q13[11] . Hypot halamic
lesions have not been f ound[132] .
Emaciation
Diencephalic Syndrome of Infancy
Diencephalic syndrome of inf ancy is a dist inct clinical condit ion charact erized by
emaciat ion, w it h loss of subcut aneous f at , pallor, mot or overact ivit y, and an
inappropriat ely jovial behavior [86, 104] . Progressive emaciat ion occurs despit e
normal f ood int ake. Nyst agmus, opt ic at rophy, and t remor are less f requent ly
encount ered manif est at ions. G row t h hormone levels may be high. The syndrome
usually appears in inf ant s aged 3 t o 12 mont hs and is caused by a slow -grow ing
ast rocyt oma of t he ant erior hypot halamus or opt ic nerve. Children w ho survive
beyond t heir second year become obese and irrit able.
Lateral Hypothalamic Syndrome

Few case report s deal w it h lat eral hypot halamic lesions causing aphagia,
cachexia, and deat h[104] . Mult iple sclerosis[67] , t umors[5] , and t rauma have
been implicat ed. Weight loss in Hunt ingt on's chorea has been ascribed t o
neuronal loss in t he lat eral t uberal nucleus[73] .
Anorexia Nervosa
Anorexia nervosa is charact erized by anorexia, w eight loss, and amenorrhea in
an ot herw ise endocrinologically normal young w oman[30] . Alt hough t he syndrome
suggest s hypot halamic dysf unct ion, in most cases no morphologic changes have
been f ound in t he hypot halamus[90] .
Disturbances of Reproductive Functions

Hypot halamic lesions f requent ly alt er reproduct ive f unct ions bot h by decreasing
gonadot ropin subst ances t hat exert a t rophic eff ect on sexual organs and by
alt ering t he neural mechanisms of int ercourse. For inst ance, t he paravent ricular
nucleus plays an import ant role in penile erect ion[4] . Several hypot halamic
nuclei, part icularly t he γ-aminobut yric acid (G ABA)-cont aining sexually dimorphic
or int ermediat e nucleus, have been f ound in young adult s t o be t w ice as large in
men as in w omen, but t he f unct ion of t hese nuclei is st ill unclear[45] .
Hypogonadotropic Hypogonadism
Hypogonadot ropic hypogonadism may f ollow any hypot halamic or pit uit ary lesion
[ 86, 133] . I t is manif est ed by amenorrhea or male gonadal dysf unct ion. When no
lesion is f ound, t he condit ion in w omen is t ermed f uncti onal hypothal ami c
amenorrhea, w hich has an endocrinologic pat t ern closely resembling t he f indings
in depression (decreased reproduct ive hormones, increased grow t h hormone and
cort isol) [13, 91] . Hypot halamic hypogonadism has been document ed in
individuals subject ed t o ext reme exercise programs, such as marat hon
runners[ 82] . More f requent reproduct ive dysf unct ion in w omen w it h epilepsy may
ref lect hypot halamic-pit uit ary changes due t o t he disease and t he eff ect of
ant iconvulsant medicat ions[64] .
Nonpuerperal Galactorrhea
Prolactin-Secreting Pituitary Tumors
Approximat ely, one-t hird of chromophobe adenomas secret e prolact in.
Structural Damage to the Infundibulum or

Hypothalamus
Such damage may int errupt t he dopaminergic pat hw ay t hat inhibit s prolact in
secret ion by t he pit uit ary. This pat hw ay originat es in t he arcuat e nucleus[86] .
Other Causes
O t her causes of nonpuerperal galact orrhea include irrit at ive lesions of t he
ant erior chest w all, t horacic spinal cord lesions, neurolept ic and cont racept ive
drugs, and hypot hyroidism[86] .
Precocious Puberty
Alt hough generally idiopat hic[40] , precocious pubert y may be due t o
hypot halamic disease or pineal t umors, some of t he lat t er aff ect ing also t he f loor
of t he t hird vent ricle [22, 107] .
Excessive or Uncontrollable Sexual Behavior

O ccasionally, t his behavior may be a consequence of lesions of t he caudal
hypot halamus[ 105] .
Other Endocrine Disturbances

Disorders such as panhypopit uit arism, hypot halamic hypot hyroidism, acromegaly,
and Cushing's syndrome are review ed in st andard endocrinology t ext books. I n
neonat es, it is import ant t o recognize and t reat t he panhypopit uit arism of
congenit al aplasia of t he pit uit ary because t reat ment is lif esaving[116] .
Disturbances of Memory
The mammillary bodies are f requent ly involved in Korsakoff 's amnest ic syndrome
and in experiment al animals t hey seem t o play an import ant role in memory
mechanisms[ 128] . How ever, w hen alcoholics w it h and w it hout amnesia are
st udied, amnesia correlat es w it h neuronal loss in t he ant erior nucleus of t he
t halamus, not in t he mammillary bodies[55] . O t her dorsal hypot halamic lesions
have been accompanied by amnesia [10, 68] . Bilat eral int errupt ion of t he
mamillot halamic t ract is considered by some t o be crit ical f or t he product ion of
memory loss by lesions in t he vent romedial hypot halamus[85] .
Disturbances of Emotional Behavior and Affect

Rage and Fear: Inappropriately Disinhibited Behavior
When caused by hypot halamic lesions, rage and f ear occur in episodic out burst s,
usually t riggered by a t hreat ening or f rust rat ing event (such as rest raint or a
delay in f eeding) and are part of a f ully coordinat ed behavioral response w it h an
int ense aut onomic component [74, 102, 104] . Bet w een t he out burst s, t he
behavior is normal and t he pat ient may realize t he inappropriat eness of such
behavior and apologize f or it . At t acks of rage may also result f rom lesions of t he
orbit of ront al cort ex, sept al region, or t emporal lobe[1] . When t he hypot halamus
is responsible, t he vent romedial region is usually involved. By cont rast ,
st imulat ion of t he post erior “sympat het ic” area elicit s responses of f ear and
horror[ 112] . Some pat ient s w it h hypot halamic lesions have t he uninhibit ed
behavior t hought t o be charact erist ic of orbit of ront al lesions[87] . Hypot halamic
hormones play a role in modulat ing social int eract ions. O xyt ocin secret ion, f or
inst ance, seems t o enhance t rust ing ot hers[120] .
Apathy and Chronic Fatigue

Apat hy may f ollow lesions of t he post erior or lat eral hypot halamus. Bilat eral
st ereot act ic lesions in t his area have been used t o t reat unmanageable
aggressive behavior due t o brain pat hology [112] . Alt hough some cases of t he
chronic f at igue syndrome have been chalked t o dysf unct ion of t he hypot halamic-
pit uit ary-adrenal (HPA) axis, including mild hypocort isolism, t his axis is normal in
pat ient s st udied early in t he process[31] .
Depression
Alt hough t here is no evidence t hat depression is caused by hypot halamic
dysf unct ion, many depressed persons have an excessively act ive HPA axis[135] .
Post mort em st udies af t er suicides have show n increased numbers of
Cort icot ropin-Releasing Hormone (CRH) neurons and increased vasopressin
expression in t he paravent ricular nucleus, increased CRH in t he cerebrospinal
f luid (CSF) and decreased CRH recept ors in t he f ront al cort ex. Challenge w it h
dexamet hasone and cort icot ropin-releasing hormone is t he most sensit ive t est
available t o det ect alt ered HPA syst em regulat ion in depression[103] .
Gelastic Seizures
Seizures accompanied by involunt ary laught er (gelast ic seizures) have been
described in associat ion w it h precocious pubert y[22] . Hypot halamic hamart oma
is most of t en t he cause and origin of t he seizures [74, 125] . The pat ient may
st are and giggle brief ly, w it hout any ot her mot or manif est at ion. Crying or
sobbing seizures may alt ernat e w it h t he gelast ic spells in t he same pat ient .
O t her pat ient s only have an int erior f eeling of pressure t o laugh, w it hout overt
manif est at ions[ 122] .
Hypot halamic hamart omas of t en cause execut ive f unct ion disorders (“f ront al lobe
syndrome”) [74, 102] . G elast ic seizures have also been described w it h cort ical
dysplasia in t he cingulat e gyrus[89] .
Headache
I n one out of seven pat ient s w it h a pit uit ary t umor, t he present ing complaint is
headache. This is usually bit emporal or bif ront al, behind t he eyes, and is t hought
t o be due t o compression of t he diaphragma sella[86] . Sudden w orsening of
headache, part icularly of a ret ro-orbit al nat ure, in a pat ient w it h a pit uit ary t umor
should raise t he diagnost ic suspicion of pit uit ary apoplexy, discussed in t he
subsequent t ext . Headache is more f requent w it h pit uit ary abscesses, a rare
condit ion, t han w it h t umors[129] .
Episodic Headaches
I ncreased perf usion in t he post erior-medial hypot halamus, dorsal t o t he
mammillary bodies, has been document ed w it h posit ron emission t omography
(PET) during some episodes of clust er headache, paroxysmal hemicrania, or t he
t ype of headache know n as Short-Lasti ng Uni l ateral Neural gi f orm Headache
Attacks wi th Conjuncti val Injecti on and Teari ng (SUNCT)[ 110] . Deep-brain
st imulat ion of t his area has result ed in improvement in pat ient s w it h t hese
disorders [78, 79] .
Chronic Pain
The hypot halamic-pit uit ary-adrenal axis seems t o be dysf unct ional in many
pat ient s w it h chronic pain syndromes, such as f ibromyalgia[16] .
Impaired Visual Acuity; Visual Field Defects

Some pat ient s w it h pit uit ary adenoma present w it h visual complaint s, and
approximat ely 15% or more have decreased visual acuit y or f ield def ect s on
f ormal t est ing (Table 17-3). Bit emporal def ect s, relat ed t o compression of t he
inf erior aspect of t he chiasm, are most common. How ever, asymmet ric t umor
grow t h may cause pref erent ial involvement of one eye, w it h unilat eral blindness,
or of t he opt ic t ract , w it h consequent homonymous hemianopia. The posit ion of
t he chiasm in relat ion t o t he sella also det ermines t he pat t ern of t he visual f ield
def ect . The chiasm lies over t he sella in 80% of brains, over t he t uberculum
sellae in 9% of brains (pref ixed chiasm), and over t he dorsum sellae in 11% of
brains (post f ixed chiasm)[ 14] . Approximat ely, 6% of pat ient s have cent ral or
t emporal scot omas, w hich may pass unnot iced if only t he periphery of t he visual
f ield is t est ed.
TABLE 17-3 Presenting Complaints in 1,000 Cases of

Pituitary Adenoma
Com plaints Num ber of Cases
Visual disturbances 421
Headache 137
Acromegaly 136
Related to hypopituitarism 95
Amenorrheay 48
Diplopia 7
Others 156
Source: Hollenhorst RW, Younger BR. Ocular

manifestations produced by adenomas of the pituitary
gland: analysis of 1,000 cases. In Kohler PO, Ross GT,
eds. Diagnosis and treatment of pituitary tumors.
Amsterdam: Excepta Medica, 1973.
O pt ic glioma of childhood is accompanied by signs of hypot halamic dysf unct ion in

approximat ely one-t hird of cases[63] . These pat ient s present w it h impaired
visual acuit y, w hich may remain st able, and opt ic disc pallor.
Diplopia; Pupillary Changes

Diplopia w it h hypot halamic-pit uit ary t umors is rare unless (a) t he t umor is large,
(b) it becomes suddenly enlarged by ischemia or hemorrhage int o it (pi tui tary
apopl exy)[ 15] , or (c) it involves primarily t he cavernous sinus (carot id aneurysm,
met ast at ic t umors). Tumors ext ending lat erally f rom t he sella t end t o cause
dysf unct ion of t he oculomot or nerve, expressed by pt osis and adduct ion
w eakness. Unilat eral hypot halamic lesions may bet ray t heir presence by causing
an ipsilat eral Horner syndrome w it h miosis.
Pi tui tary apopl exy causes headache or ret ro-orbit al pain relat ed t o compression
of t he opht halmic branch of t he t rigeminal nerve, vomit ing, visual f ield def ect s or
reduced acuit y, and ocular mot or paresis, most of t en of t he oculomot or nerve,
locat ed more medially in t he cavernous sinus[15] . Some pat ient s are conf used,
most of t en f rom t he syst emic met abolic derangement t hat of t en at t ends pit uit ary
inf arct ion of hemorrhage or f rom compression of t he hypot halamic region.
Seldom, ot her causes are at w ork, such as non-convulsive st at us epilept icus[33] .
Rarely, some of t he sympt oms may be relat ed t o carot id compression [134] .
O f t en
due t o hemorrhage w it hin a pit uit ary adenoma, inf arct ion of t he t umor w it h
sudden expansion is also f requent [23, 38, 57, 76, 134] . I t has been report ed
af t er hormonal st imulat ion, eit her physiologic or in t he course of endocrine
t est ing [38, 76] . When t he cause is an ischemic prolact inoma, rapid improvement
may result f rom bromocript ine administ rat ion. Most of t en, t his condit ion requires
sw if t surgery[15] .
TABLE 17-4 Clinical Findings w ith Lesions in Various

Regions of the Hypothalamus or in the Pituitary Gland
Anterior hypothalamus (“parasympathetic area”)

Hyperthermia
Insomnia
Diabetes insipidus
Emaciation
Posterior hypothalamus (“sympathetic area”)
Hypothermia
Poikilothermia
Hypersomnia, coma
Apathy
Ipsilateral Horner syndrome
Medial hypothalamus
Hyperdipsia (excessive water intake)
Diabetes insipidus
Syndrome of inappropriate antidiuretic hormone
secretion
Obesity
Amnesia
Rage
Dwarfism
Arcuate nucleus and infundibulum
Hypopituitarism
Lateral hypothalamus
Adipsia (reduced water intake)
Emaciation
Apathy
Pituitary gland
Visual field defects
Headache
Decreased hormonal action
Dwarfism
Hypogonadism
Hypothyroidism
Glucocorticoid deficiency (usually with
panhypopituitarism)
Excessive hormonal secretion (adenomas)
Cushing's syndrome
Gigantism (child), acromegaly (adult)
Hyperprolactinemia
Clinical Findings Resulting from Lesions in Various

Areas of the Hypothalamus and in the Pituitary Gland
I n t he previous sect ion, t he present ing complaint s w ere discussed as a means t o
arrive at t he correct localizat ion of t he lesion. I n Table 17-4, t he reverse pat h is
f ollow ed: given t he sit e of t he lesion, t he most likely clinical f indings are list ed.
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> Table of C ontents > C hapter 18 - The Anatom ic Loc aliz ation of Les ions in the Thalam us
Chapter 18
The Anatomic Localization of Lesions in the
Thalamus
Functional Anatomy of the Thalamus

The paired t halamic nuclei are egg-shaped st ruct ures of gray mat t er locat ed on
bot h sides of t he t hird vent ricle. They represent t he largest port ion of t he
diencephalon; ot her diencephalic st ruct ures are t he epit halamus (pineal and
habenular complex), t he subt halamic nucleus, and t he hypot halamus. The
t halamus plays a major role in cort ical act ivat ion[100] . I t project s t o t he cort ex in
a highly organized f ashion. Charact erist ically, t halamic connect ions are
reciprocal, t hat is, t he t arget of t he axonal project ion of any given t halamic
nucleus sends back f ibers t o t hat nucleus. Nevert heless, t halamocort ical
project ions are of t en larger t han t heir cort icot halamic count erpart s (e. g. , t he
geniculocalcarine project ion). Anat omically and f unct ionally, f our regions can be
dist inguished in t he t halamus: ant erior, post erior, medial, and lat eral, part ially
separat ed f rom each ot her by w hit e mat t er laminae t hat are visible t o t he naked
eye[ 72, 127] . I n t he core of t he t halamus, a f if t h region is encased by t hese
laminae, t he int ralaminar nuclei[184] . Finally, t he lat eral aspect of t he t halamus
is covered by a layer of myelinat ed axons, t he ext ernal medullary lamina,
housing in it s core clust ers of cells, t he ret icular nucleus of t he t halamus[173] . A
simplif ied account of t he t halamic nuclei and t heir connect ions, pert inent t o
clinical localizat ion, is given in Table 18-1. Figure 18-1 illust rat es t he posit ion
and main cort ical project ions of t he t halamic nuclei.
From a diagnost ic st andpoint , t he complex t halamic anat omy can be divided int o
t he f ollow ing f our main regions:
1. The midline, int ralaminar, ret icular, and some areas of t he vent ral ant erior
nuclei mediat e general cort ical alert ing responses and are t ermed
nonspeci f i c thal ami c nucl ei. How ever, t he locat ion and role of t halamic cells
providing nonspecif ic cort ical act ivat ion is st ill being w orked out [77] . By
cont rast , speci f i c t halamic nuclei receive sensory inf ormat ion f rom t he body,
process it , and project t he pert inent out put t o specif ic areas of t he cort ex,
such as t he somat osensory area and visual cort ex. The nonspecif ic t halamic
nuclei receive st rong project ions f rom t he midbrain ret icular f ormat ion and
f ibers f rom t he spinot halamic t ract as w ell as f rom ot her sensory pat hw ays.
Some st imuli (e. g. , audit ory, pain) excit e t his alert ing syst em more easily
t han ot hers (e. g. , visual). These nuclei project back t o t he midbrain and t o
t he specif ic t halamic nuclei. Lesions t hat involve t hese st ruct ures bilat erally
cause impairment of alert ness.
2. The medial (dorsomedial) and ant erior t halamic nuclear groups play an
import ant role in memory and emot ions[93] . They are connect ed w it h t he
hypot halamus, t he “limbic lobe” (cingulat e gyrus, medial t emporal region,
insula), and t he f ront al lobe. The dorsomedial nucleus mediat es emot ions,
t he secondary eff ect of pain, t he sleep-w ake cycle and execut ive f unct ions
[ 7, 150, 157, 163, 181] . Lesions of t he ant erior nucleus are more
consist ent ly associat ed w it h memory and execut ive f unct ion loss [55, 63,
68] .
3. The vent ral lat eral and basal nuclear groups are concerned w it h t he
processing of sensory inf ormat ion and relaying it t o t he cort ex and w it h
sensorimot or cont rol[104] . Relaying sensory inf ormat ion t o t he cort ex is
eff ect ed mainly by t hree nuclear groups, as f ollow s:
The ventral posterior nuclear group, w here t ast e and somat osensory
inf ormat ion is
elaborat ed and project ed t o t he somat osensory cort ex of t he pariet al lobe.

Wit hin t he t halamus, lat eral inhibit ion increases sharpness in spat ial
localizat ion. I nf ormat ion f rom recept ors in t he head reaches t he vent ral
post erior medial nucleus t hrough t he t rigeminot halamic pat hw ays. The vent ral
lat eral nucleus processes somat osensory inf ormat ion conveyed by t he
spinot halamic t ract and medial lemniscus. A group of nuclei dorsal t o t he
medial geniculat e body, and called t he ventral medi al nucl eus, part icipat es
in t he percept ion of pain and t emperat ure, part icularly w ell-localized, sudden
pain[ 11] .
TABLE 18-1 Source and Destination of Thalamic

Connections*
T halam ic
Afferent Efferent
Regions and
Connections Connections
Nuclei
Anterior
Mammillary bodies
Anterior (mammillothalamic Cingulate
nucleus tract) gyrus
Hippocampus (fornix)
Medial
Frontal lobe Frontal lobe

Amygdala Lateral
Inferior temporal hypothalamus
Medial (or
cortex Ventral
dorsal) nucleus
Centromedian anterior
thalamic nucleus thalamic
Zona incerta nucleus
Hypothalamus
Dorsal medial
Midline nuclei Hypothalamus
thalamic
nucleus
Lateral
Dorsal
Cingulate
gyrus,
Posteromedial
Lateral posterior part
temporal region
dorsal nucleus Mesial
(fornix)
parietal
cortex
Ventral
Orbitofrontal
Pallidum cortex
Ventral Intralaminar
Substantia nigra
anterior thalamic
Dorsal medial
nucleus nuclei
thalamic nucleus
Dorsal medial
thalamic
nucleus
Pallidum (lenticular
fasciculus; ansa
lenticularis)
Paracentral
Ventral Contralateral
cortex, areas
lateral nucleus cerebellum
4 and 3a
(dentatorubrothalamic
tract; thalamic
fasciculus)
Contralateral
receptors for joint
position, vibration,
epicritic touch
(medial lemniscus)
Contralateral
receptors for touch,
Ventral heat and cold, painful Postcentral
posterior stimuli (spinothalamic gyrus, areas
lateral nucleus tract) 3b, 1, and 2
Dorsal medial
thalamic nucleus
Septal region
Frontal lobe (medial
forebrain bundle)
Somatosensory
cortex
Contralateral spinal
trigeminal nucleus
(face, painful stimuli)
Contralateral main
Postcentral
Ventral trigeminal nucleus
gyrus; lower
posterior (touch
lateral, “face”
medial nucleus proprioception)
region
Mesencephalic
trigeminal nucleus
(bite
mechanoreceptors)
Posterior
Dorsal
Superior and
Lateral
inferior
posterior Pulvinar
parietal
nucleus
lobules
Pulvinar
Superior and
Medial geniculate inferior
Medial
body parietal
lobules
Posterior
Lateral geniculate
Lateral temporal
body
region
Peristriate
Ventral lateral
Inferior occipital
thalamic nucleus
cortex
Ventral
Other
Posterior Bilateral receptors of
thalamic
thalamic zone noxious stimuli
nuclei
Transverse
Medial Bilateral hearing
temporal
geniculate (brachium of the
gyrus of
body inferior colliculus)
Heschl
Lateral
Contralateral visual Calcarine
geniculate
field (optic tract) cortex
body
Intralaminar
Striatum:
Caudate,
Centromedian
Pallidum putamen
and
Frontal lobe, areas 4 Ventral
parafascicular
and 6 anterior
nuclei
thalamic
nuclei
Ventral
Smaller Brainstem reticular anterior
intralaminar formation; thalamic
nuclei spinothalamic tract nuclei
Orbital cortex
Reticular Thalamocortical Thalamic

nucleus projection nuclei
*In parentheses is the name of the white matter bundles

that correspond to each connection.
The medial geniculate body, w here audit ory inf ormat ion f rom t he inf erior
colliculus passes on t o t he t ransverse t emporal gyrus, buried in t he dept h of
t he Sylvian f issure. Lesions of t his t halamic nucleus are discussed in Chapt er
11.
The lateral geniculate body, relay st at ion f or t he visual pat hw ay, w hich
receives f rom t he ret inal ganglion cells t he axons t hat f orm t he opt ic t ract
and f rom w hich originat es t he axons t hat project t o t he calcarine cort ex
t hrough t he opt ic radiat ions. Lesions of t his t halamic nucleus are discussed
in Chapt er 7.
Sensorimot or cont rol is carried out by t he more ant erior of t he vent rolat eral
nuclei (vent ral lat eral and vent ral ant erior) and perhaps by t he int ralaminar
nuclei[ 89, 120] . The vent rolat eral nucleus has an oral, a medial, and a
smaller caudal port ion. The medial port ion receives input f rom t he cerebellum
and project s t o t he precent ral cort ex or primary mot or cort ex (area 4). The
largest oral port ion receives input f rom t he globus pallidus and project s
most ly t o t he premot or cort ex. The vent rolat eral nucleus also receives
inf ormat ion f rom musculoskelet al syst em mechanorecept ors; it cont ribut es t o
t he coordinat ion of f iner, dist al mot or movement s w it h t he proximal axial
movement s t hat support t hem. The vent ral ant erior nucleus may play a role in
volunt ary at t ent ion. I t has st rong connect ions w it h t he pallidum, medial
t halamic nuclei, and f ront al cort ex.
Anat omically, t he t halamus const it ut es t he keyst one f or t w o large
sensorimot or cont rol
loops: (a) t he cerebello-rubro-t halamo-cort ico-pont ocerebellar loop and (b)

t he cort ico-st riat o-pallido-t halamo-cort ical loop. Alt hough t he physiologic role
of each loop is f ar f rom clear, it is know n t hat lesions in each loop cause
diff erent syndromes. O bviously, t he anat omy allow s ample possibilit ies f or
lesions t o aff ect bot h loops. Sympt oms and signs derived f rom cerebellar
lesions are discussed in Chapt er 16. Those derived f rom basal ganglia
lesions are discussed in Chapt er 19. Mot or f indings t hat point t o t he
t halamus as t he sit e of t he lesion are given pref erent ial at t ent ion here.
4. The f ourt h main region of t he t halamus comprises t he dorsolat eral and
post erior nuclear groups, part icularly t he pulvinar, w hich seem t o modulat e
occipit o-t emporo-pariet al cort ical at t ent ion[129] . As such, it f acilit at es visual
at t ent ion and t he cort ical at t ent ion needed f or language-relat ed sensory
t asks in t he lef t hemisphere and visuospat ial t asks in t he right [37, 76] . This
area is much bet t er developed in humans t han in low er mammals[32, 34] .
During ont ogenesis, it is t he last region t o reach adult morphology.
Vascular Supply of the Thalamus

Cerebrovascular disease is t he most common cause of discret e t halamic
pat hology result ing in signs and sympt oms of localizing value[158] . I nf arct s are
more common t han hemorrhages. Theref ore, some know ledge of t he vascular
supply of t he t halamic nuclei helps great ly t o underst and t he so-called t halamic
syndromes and t he localizat ion of t halamic lesions.
The t halamic art eries arise f rom t he post erior communicat ing art eries and f rom
t he perimesencephalic segment of t he post erior cerebral art eries [24, 142, 143,
144] . The origin and t errit ory of supply of t he various t halamic vessels diff er in
each person. For inst ance, w hen t he post erior communicat ing art ery is small or
absent , art erial t w igs f rom t he post erior cerebral art ery supply t he t halamic
t errit ory t hat is ot herw ise supplied by branches of t he post erior communicat ing
art ery. Table 18-2 summarizes t he more common vascular pat t erns (Fig. 18-2).
I n bot h t he t able and f igure, t he segment of t he post erior cerebral art ery
proximal t o t he ost ium of t he post erior communicat ing
art ery has been t ermed t he basi l ar communi cati ng artery[ 24] .
FI G URE 18-1 A: Thalamic nuclei. Top, Front al sect ion of t he t halamus at t he
level of t he dashed line on t he f igure at t he bot t om. Bot t om, Lat erodorsal
view of t he t halamus, show ing t he posit ion of t he t halamic nuclei B: Aff erent s
and cerebral cort ical project ions of t he t halamic nuclei. Top, Main sources of
aff erent s t o t he diff erent t halamic nuclei, illust rat ed on t he lat eral and medial
aspect s of t he cerebral hemispheres (bot t om). DM = dorsomedi al (Modif ied
f rom Carpent er MB. At het osis and t he basal ganglia. Arch Neurol Psychi atry.
1950; 63: 875. )
Localization of Ischemic Thalamic Lesions

I n localizing ischemic lesions of t he t halamus, several point s should be kept in
mind.
1. The art erial supply f or most of t he t halamus arises f rom t he vert ebrobasilar
syst em, in some cases w it h a small cont ribut ion f rom t he post erior
communicat ing art ery[24] . O nly t he lat eral port ion and t he hilium of t he
lat eral geniculat e body are usually f ed by t he ant erior choroidal art ery, a
branch of t he int ernal carot id art ery.
2. Except f or t he lat eral geniculat e body, t he middle cerebral and ant erior
choroidal art eries do not supply t he t halamus t o such an ext ent t hat t halamic
inf arct ion w ould result f rom occlusion of t hese vessels[142] . Some int ernal
capsular dysf unct ion, how ever, may result f rom t he occlusion of t halamic
vessels[ 125] . I n rare cases, t he ant erior cerebral art ery may cont ribut e t o
t he supply of t he post erolat eral t halamus t hrough a post erior pericallosal
vessel, w hich is anast omot ic w it h t he post erolat eral choroidal art ery.
3. The paramedian t halamic vessels of t en arise f rom a single pedicle t hat
originat es in one of t he basilar communicat ing art eries (see Fig. 17-2).
Theref ore, unilat eral post erior cerebral art ery occlusions may result in
bilat eral paramedian t halamic inf arct s[24] .
The arteri al terri tory responsible f or a t halamic ischemic inf arct may be inf erred
f rom t he clinical f indings, as f ollow s.
FI G URE 18-2 Art erial supply of t he t halamus. I nset : Variat ions in t he origin
of t he paramedian art eries, w hich may arise f rom each basilar
communicat ing art ery (A), f rom a single pedicle originat ing in one basilar
communicat ing art ery (B), or f rom a vascular arcade connect ing bot h basilar
communicat ing art eries (C). DM = dorsomedi al; LG = l ateral geni cul ate; MG
= medi al geni cul ate. (Modif ied f rom Cast aigne P, et al. Paramedian t halamic
and midbrain inf arct s: Clinical and neuropat hological st udy. Ann Neurol
1981; 10: 127. )
TABLE 18-2 Vascular Supply of the Thalamus
Nam e of vessel Origin Distribution
Thalamic nuclei
Posterior Reticular
Polar arteries communicating Ventral anterior
artery Medial
(anterior portion)
Thalamic nuclei
Reticular
Ventrolateral
Medial
Basilar Midline
communicating (paraventricular)
artery (portion Centromedian
of posterior Other structures
Paramedian Red nucleus
cerebral artery
thalamomesencephalic (superior-median
proximal to
arteries portion)
ostium of
posterior Interpeduncula
communicating nucleus
artery) Decussation of
the superior
cerebellar
peduncle
Third nerve
nucleus
Posterior
cerebral
Thalamogeniculate artery, Ventral caudal
pedicle proximal to nuclei
geniculate
body level
Thalamic nuclei
Centromedian
Ventral
posterior medial
Medial
geniculate body
Posterior
cerebral Pulvinar
artery, just Medial
Posteromedial distal to (posterior
choroidal arteries ostium of portion)
posterior Anterior
communicating Other structures
artery Crus cerebri
Subthalamic
nucleus
Substantia
nigra
Red nucleus
(lateral)
Thalamic nuclei
Posterior Lateral
cerebral artery geniculate body
(between Pulvinar
Posterolateral lateral (inferolateral
choroidal arteries geniculate portion)
body and Laterodorsal
dorsal pulvinar Other structures
level) Hippocampus
Choroid plexus
Paramedian Territory
I nf arct s here t end t o also involve t he paramedian region of t he midbrain. Most
of t en, t he syndrome is composed of t he clinical t riad of somnolent apat hy,
memory loss, and abnormalit ies of vert ical gaze[153, 196] . Bilat eral medial
t halamic inf arct s account f or t he behavioral syndrome, and lesions in t he area of
t he rost ral int erst it ial nucleus of t he medial longit udinal f asciculus account f or t he
vert ical gaze palsy[196] . The f ollow ing f indings may result , depending on t he
ext ent and locat ion of t he lesion [10, 14, 24, 61, 62, 65, 85, 175, 196] :
Transient loss of consciousness or somnolence; occasionally akinet ic mut ism
Behavioral changes (conf usion, agit at ion, aggression, lack of init iat ive,
disorient at ion, apat hy, manic delirium, a f ront al lobe-like syndrome[12] )
Recent memory loss (w it h ant erograde and ret rograde component s);
persist ent memory loss
is observed only w it h damage of t he dominant ant erior nucleus or

mamillot halamic t ract [175] .
Vert ical gaze and convergence disorders (and occasionally blepharospasm)
Cont ralat eral hemiat axia, ast erixis, or mot or w eakness
Delayed act ion t remor (occasionally myoclonus or at het osis) in t he
cont ralat eral limbs
This syndrome is of t en due t o embolic occlusion of t he t op of t he basilar art ery

or local at heroma at t he origin of t he post erior cerebral art ery [14, 19, 117,
175] .
Thalamogeniculate (Lateral Thalamic or Inferolateral

Thalamic) Territory
I schemia in t his t errit ory (vent ral post erior nucleus, vent ral lat eral nucleus, and
subt halamic region) causes some of t he component s of t he classic t halamic
syndrome described by Dejerine and Roussy [14, 20, 61, 62, 110, 111, 118, 169,
198] :
Hemianest hesia (occasionally, propriocept ion is spared)

Transient slight hemiparesis
Hemiat axia
Hemiat axia-hypest hesia syndrome
Lack of nonvolit ional ut ilizat ion of t he cont ralat eral body (damaged
“aut omat ic pilot ”)
Dysequilibrium (“t halamic ast asia”)
Choreoat het oid movement s
At het oid post ure (“t halamic hand”)
Paroxysmal pain (t halamic pain)
Homonymous hemianopia (of t en due t o simult aneous medial occipit al
inf arct ion)
All t hese f indings occur on t he side of t he body cont ralat eral t o t he lesioned
t halamus. The more severe f orms of t he syndrome (compl ete geni cul othal ami c
i nf arct) accompany proximal occlusion of t he post erior cerebral art ery[61] .
Part ial f orms (parti al geni cul othal ami c i nf arct) result f rom lacunar inf arct ion
rest rict ed t o one of t he penet rat ing t halamogeniculat e vessels [20, 61, 126] and
result in pure sensory or sensorimot or st roke. Disease of such small perf orat ing
art eries of t en accompanies diabet es and chronic hypert ension.
I solat ed hemiat axia and ipsilat eral sensory loss (t he hemiat axia-hypest hesia
syndrome or t halamic at axia syndrome) may occur w it h inf arct ion in t he
t halamogeniculat e t errit ory t hat involves t he lat eral part of t he t halamus (vent ral
post erior nucleus and vent ral lat eral nucleus)[ 118, 169] . The sensory dist urbance
may be purely subject ive, may aff ect light t ouch, pain, and t emperat ure sense,
or aff ect light t ouch, pain, t emperat ure, posit ion, and vibrat ion sense. The
cont ralat eral “cerebellar” dysf unct ion and sensory loss is due t o a lesion of t he
dent at orubrot halamic and ascending sensory pat hw ays int o t he t halamus[169] .
Also, recurrent pure sensory t ransient ischemic at t acks (t ransient
hemihypest hesia) may occur w it h vent ropost erolat eral nucleus ischemia[49] .
Tuberothalamic (Anterolateral Thalamic) Territory

I nf arct s in t his t errit ory are due t o t halamopolar art ery lesions and result
primarily in neuropsychologic dysf unct ion [55, 61, 62, 63] . The f ollow ing f indings
may result :
Apat hy and verbal perseverat ion, as part of execut ive f unct ion impairment
Ant erograde memory loss
Facial paresis f or emot ional movement
O ccasionally, hemiparesis and visual f ield def ect s (sensat ion spared)
The superimposit ion of t emporally unrelat ed inf ormat ion
Dysphasia w it h lef t -sided lesions
Hemineglect and impaired visuospat ial processing w it h right -sided lesions
Bilat eral polar art ery t halamic inf arct s result in apat hy, abulia, “f ront al lobe”
def icit s, let hargy, and impaired memory[80] .
Territory of the Posterior Choroidal Arteries

These vessels supply t he lat eral geniculat e body, pulvinar, post erior t halamus,
and a small post erior port ion of t he hippocampus and parahippocampal gyri[133] .
I n lat eral post erior choroidal art ery t errit ory inf arct ion, t he most common clinical
manif est at ions include t he f ollow ing:
1. Homonymous quadrant anopsia, superior or inf erior, or, rarely but part icularly
suggest ive of involvement of t he lat eral geniculat e body in t his t errit ory, a
homonymous horizont al sect oranopsia, t ubular or shaped like a w edge
2. Decreased opt okinet ic nyst agmus w hen moving t he drum t o t he side of t he
lesion
3. Hemisensory loss w it h mild hemiparesis
4. Mild hemiparesis, accompanied by sensory loss (alt hough no involvement of
t he int ernal capsule is det ect ed by magnet ic resonance imaging (MRI ))
5. Transcort ical aphasia
I solat ed medial post erior choroidal art ery t errit ory inf arct ion has not been
reliably document ed.
Miosis, occasionally ipsilat eral, has been described w it h t hese lesions[133] .

Thalamic hemorrhage is discussed in Chapt er 21.
Clinical M anifestations of Lesions in the Thalamus

The f ollow ing considerat ions f acilit at e t he underst anding of t he clinical
manif est at ions of t halamic lesions:
1. Because t he t halamus is small, several of the nucl ei and even several of t he

f unct ional regions out lined earlier are usually aff ect ed simult aneously, even
by discret e lesions such as inf arct s. Because art eriolar vascular t errit ories
cross t he nuclear boundaries, as a rule ischemic disease aff ect s several
nuclei, of t en part ially[24] . I n addit ion, many lesions are not rest rict ed t o t he
t halamus, but involve nei ghbori ng areas of t he brain as w ell. For inst ance,
paramedian t halamic vascular lesions t end t o aff ect also t he midbrain as
w ell, w it h a result ant decrease in t he level of alert ness t o t he point of
coma[ 24] . Theref ore, ot her mot or or sensory f indings t hat w ould point t o
t halamic involvement cannot be elicit ed. Lat erally locat ed lesions may disrupt
t he int ernal capsule, t hereby causing mot or and sensory def icit s[64] t hat
mask t he def icit s charact erist ically present w it h t halamic involvement . For
inst ance, t he t endency t o avoid using an ot herw ise st rong limb cont ralat eral
t o a lesioned vent ral lat eral t halamic area (“t halamic neglect ”) is not manif est
if capsular involvement has result ed in a hemiparesis. Lesions ext ending
inf eriorly may yield hemiballismus, f or w hich t he subt halamic lesion is
probably primarily responsible. Lesions in t he t errit ory of t he lat eral
post erior choroidal art ery may cause memory loss t hrough t he involvement of
t he parahippocampal gyrus[133] .
2. Except f or sensory def icit s, unilat eral t halamic lesions result in t ransient
def icit s. By cont rast , bilat eral lesions or unilat eral lesions, such as
hemorrhages or t umors, w hich press against t he cont ralat eral t halamus or
impinge on t he midbrain, may render t he pat ient comat ose or akinet ic and
mut e.
3. Timing has a part icular impact on t he clinical expression of t halamic lesions.
As t he eff ect s of an acut e lesion recede, neglect may disappear, inabilit y t o
w alk may yield t o mild at axia, and hemisensory loss diminishes. O t her
f indings, how ever, part icularly t he so-called posit ive sympt oms (t remor,
pain), usually become more pronounced w it hin a f ew w eeks af t er t he injury.
Discret e lesions in various regions of t he t halamus, and, more recent ly, deep
brain st imulat ion (DBS) t hrough implant ed elect rodes, are increasingly used f or
t he t reat ment of parkinsonian and essent ial t remor[139, 189] , dyst onia[88] ,
pain[ 35] , epilepsy[179] , and t he manif est at ions of G illes de la Touret t e's
syndrome[ 178] . Treat ment of t he t remor is t he most ext ensively used and best
underst ood DBS t halamic procedure. Essent ial t remor can be t reat ed by DBS
w it h elect rodes in t he vent rolat eral nucleus. The vent rolat eral nucleus includes
t he nuclei Vent ralis I nt ermedius (Vim) and vent ralis oralis post erior (Vop). The
ideal locat ion of t he st imulat ing elect rodes seems t o lie in t he Vop nucleus
immediat ely ant erior t o t he cerebellar receiving area, Vim[139] . I n addit ion t o t he
t arget eff ect , some of t hese procedures have produced ot her sympt oms or
signs, w hich w ill be ment ioned under t he appropriat e heading.
Disturbances of Alertness
Sudden bilat eral paramedian t halamic lesions, such as inf arct s, may cause a
decreased level of alert ness ranging f rom somnolence t o coma [24, 61, 101] ,
generally t ransient . Prolonged coma may result if t he lesion ext ends int o t he
midbrain t egment um. These pat ient s of t en have oculomot or paresis[24] . By
cont rast , pat ient s w it h pure t halamic involvement have very small react ive pupils
(“diencephalic pupil”), and t heir ext raocular movement s, elicit ed by t he doll's
head maneuver, are f ull[147] . Akinet ic mut ism, discussed in Chapt er 22, may
f ollow bilat eral paramedian t halamic lesions[24, 164] , as in t he not ed Karen
Q uinlan case[87] . O t her report ed dist urbances include inversion of t he
nyct hemeral rhyt hm and dissociat ion of sleep st ages, det ect ed by
elect roencephalography, bet w een t he t w o hemispheres[79] . The hemisphere
aff ect ed by a t halamic t umor show ed earlier onset of deeper sleep st ages.
The int ralaminar, ret icular, and vent ral ant erior nuclei seem t o play t he great est
role in mediat ing normal alert ness[17, 173] . Lesions in t he region of t he
int ralaminar nuclei cause drow siness[70] . Elect rical st imulat ion of t his region
induces arousal f rom sleep[197] . Bilat eral paramedian t halamic inf arct ion may
cause severe apat hy and a bromocript ine-responsive compulsive t endency t o
assume a sleeping post ure (“presleep behavior”)[ 25] . I n pat ient s w it h
paramedian t halamic lesions and dayt ime hipersommia, rapid eye movement
(REM) sleep is normal, but w akef ulness, sleep spindling, and st ages of deep
sleep are all reduced, suggest ing t hat t he medial t halamus
is t he “f inal common pat hw ay” f or bot h maint enance of w akef ulness and
promot ion of non-REM sleep[7, 166] . Low -f requency (3/ s), high-int ensit y
combined st imulat ion of t he right cent romedian nucleus and lef t nonspecif ic
mesencephalic ascending pat hw ays elicit ed a response similar t o t he t ypical
absence at t ack[187] . The dorsomedial t halamic nucleus can be at rophic and
hypomet abolic on t he side of chronic t emporal lobe epilepsy[78] .
A prion disease (most ly conf ined t o t he ant erior vent ral and dorsomedial nuclei)
has been described (f atal f ami l i al i nsomni a) in w hich progressive insomnia (w it h
loss of slow -w ave sleep and abnormal REM sleep behavior w it h lack of
veget at ive and endocrine circadian rhyt hms) and dysaut onomia (hyperhidrosis,
hypert hermia, t achycardia, hypert ension, miosis, sphinct er dist urbances) w ere
associat ed w it h impaired arousal during dayt ime, dreamlike st at es, mot or
abnormalit ies (dysart hria, at axia, pyramidal dysf unct ion, int ent ion t remor,
myoclonus), and event ual coma and deat h [27, 36, 103, 116, 174] . The age of
onset of t he disease varies bet w een 37 and 64 years; t he course averages 13
mont hs w it h a range of 7 t o 25 mont hs. The disease has been relat ed t o a
mut at ion at codon 178, or 200 in t he prion prot ein gene (PRNP).
DBS w it h elect rodes in t he cent romedian-DM t halamic region caused a change in
penile erect ion, f acilit at ing it in a pat ient and inhibit ing it in anot her[178] . I n bot h
t hese cases, DBS improved t he t ics of G illes de la Touret t e syndrome. Kleine-
Levin syndrome, w hich is charact erized by episodes of somnolence,
hyperphagia, impaired recent memory, and hypersexual behavior, t radit ionally
believed t o be relat ed t o hypot halamic disease, may be due t o paramedian
t halamic lesions[23] .
Disturbances of Mood and Affect

Apat hy, disint erest , and lack of drive f or mot or expression have been report ed
w it h lesions of t he paramedian region of t he t halamus [12, 24, 61, 85] . Less
of t en, such lesions may cause agit at ion, dysphoria, or an acut e conf usional
st at e[ 12, 57] , and even undue jovialit y, accompanied by conf abulat ion[24] .
Similar manif est at ions of bilat eral medial t halamic damage may be int erpret ed as
a part ial ver-Bucy syndrome Klüver-Bucy syndrome, described in a pat ient w it h
chronic amnesia, dist ract ibilit y, hyperoralit y, aff ect ive dyscont rol, and a socially
inappropriat e behavior[130] . A manic-like st at e w it h disinhibit ion aff ect ing speech
(w it h logorrhea, delirium, joking, laughing, inappropriat e comment s, and
conf abulat ion) has been described w it h right t halamic lesions[12, 90] . A pat ient
ment ioned having lost t he pleasure involved in reading af t er a lef t ant erior
t halamic inf arct [31] . The ipsilat eral cingulat e gyrus w as hypomet abolic. I n
schizophrenia, a disorder w it h alt ered aff ect and execut ive f unct ion, neuronal
loss has been f ound in t he dorsomedial and ant erior nuclei of t he t halamus by
some[ 148, 199] , but not by ot hers[44] .
Memory Disturbances
Recent memory may be t ransient ly or permanent ly impaired by lesions of t he
ant erior or medial t halamic nuclear region [24, 62, 63, 74, 123, 188] . This def icit
appears most consist ent ly w it h bilat eral lesions but may be associat ed w it h even
unilat eral lesions of eit her t halamus [24, 31, 140] . I n some cases, t he t ransient
nat ure of t he def icit has prompt ed t he diagnosis of t ransient global amnesia,
alt hough most pat ient s w it h t his disorder do not present evidence of t halamic
disease [59, 151] .
The proposed anat omic basis f or a permanent amnest ic syndrome af t er bilat eral
ant erior t halamic inf arct ions is combi ned damage t o hippocampal-t halamic
pat hw ays t hrough t he mammillot halamic t ract and medial t emporal-t halamic
pat hw ays t hrough t he inf erior t halamic pedicle [63, 67, 105, 185, 190] . These
pat hw ays are closely adjacent in t he ant erior t halamus, and bilat eral lesions t hat
cause amnesia are f ound in t his region, w hereas bilat eral medial t halamic lesions
t hat do not cause amnesia are locat ed more post eriorly [63, 105, 121, 190] .
Korsakoff 's amnesia correlat es w it h neuronal loss in t he ant erior t halamic, but
not dorsomedial, nuclei[68] . Pure amnesia has also been described af t er a
unilat eral lef t polar t halamic inf arct aff ect ing t he ant erior t halamic nuclei and
adjacent mammillot halamic t ract [31] . Lesions involving t he lef t t halamus aff ect
mainly verbal memory[55, 128] , w hereas t hose in t he nondominant paramedian
t halamic region impair memory relat ed t o visuospat ial t asks (nonverbal memory)
[ 12, 145, 170, 171, 195] .
Thalamic amnesia is charact erized by def icit s in ant erograde verbal and visual
learning and by ret rograde amnesia, but mot or learning is preserved[63] .
Pat ient s w ho are alert and act ive usually perf orm adequat ely in t est s of
immediat e memory, such as digit span. Charact erist ically, t he amnesia is most
prof ound f or event s t aking place af t er t he injury (ant erograde amnesia
or recent memory loss), alt hough somet imes it includes inf ormat ion acquired
days t o years prior t o t he injury (ret rograde amnesia) [55, 81, 115, 200] .
Disorient at ion t o t ime is common. Wit h t halamic lesions, t he cont ent of recall is
not as aff ect ed as t he t emporal order of t he it ems st ored in memory, be t hey
verbal or nonverbal it ems. Theref ore, t he pat ient s may ret rieve f act s, but in a
disorganized f ashion and out of cont ext [55, 167] . Some pat ient s seem t o be
aw are of t heir def icit [200] , and ot hers do not [188] . Whet her t his can be
account ed f or by diff erences in t he sit e or t he ext ent of t he lesion remains t o be
det ermined.
Some unusual pat t erns of memory loss and recovery have been described w it h
t halamic lesions. A pat ient w it h bilat eral medial t halamic lesions recognized by
t heir voices relat ives w hom he had f ailed t o ident if y visually (prosopagnosia)
[ 115] . Anot her pat ient 's ret rograde amnesia improved suddenly one year af t er a
lef t ant erior t halamic inf arct ion, w hen he w as exposed t o an event t hat t riggered
t he recall of a f lood of previously f orgot t en aut obiographical det ail[102] . The
resemblance w it h Proust 's recollect ion t riggered by t he t ast e of aunt Leonie's
“pet it e madeleines” has led t o t he t erm “peti te madel ei nes phenomenon” f or t his
remarkable present at ion[102] .
Conf abulat ion, or f alsif icat ion of memory occurring in clear consciousness, is
f requent ly present w it h t halamic amnesia [12, 55, 160, 161] . Pat ient s may
conf abulat e spont aneously or w hen asked t o recall some f act s[160, 161] .
Part icularly t hose w ho conf abulat e spont aneously seem t o have an impaired
abilit y t o order in t ime f act s ret ained in memory[55, 161] . Part of t he problem
has t o do w it h ident if ying t he relevance of it ems st ored in memory t o t he current
cont ext . I t ems of memory t hat are not appropriat e f or t he here and now f ind
t heir w ay int o t he pat ient 's verbal out put or are manif est ed by behavior t hat
relat es t o past experiences, but not t o w hat is now appropriat e.
Thalamic lesions may cause sensory loss, of t en accompanied by parest hesias
and pain.
Paresthesias and Pain

Clinically, small lesions in t he vent ral post erior lat eral nucleus of t he t halamus
may yield only cont ralat eral parest hesias t hat lack “object ive” sensory loss w hen
t est ed at t he bedside[48] . Such parest hesias t end t o occur on one side of t he
f ace, part icularly around t he mout h, and in t he dist al port ion of t he limbs.
O ccasionally, t his cheiro-oral or dist al dist ribut ion of t he parest hesias may
suggest a more dist al lesion (e. g. , radiculopat hy)[ 94] . These areas of t he body
have t he largest represent at ion in t he t halamic sensory nuclei. When t he t runk is
also numb, t he subject ive f eeling of numbness may st op abrupt ly in t he midline,
alt hough on object ive t est ing t he sensory loss of t en f ades t ow ard t he
midline[ 125] . Such a “t halamic midline split , ” w hich is absent w it h pariet al
lesions, has been t hought t o have some clinical value in ident if ying t he sit e of t he
lesion[ 126] . The numb areas of t he body may f eel sw ollen, enlarged, short ened,
t w ist ed, or t orn, or t hey may t ingle. O bject s held w it h t he limb cont ralat eral t o
t he lesion may f eel abnormally heavy. Finally, t he pat ient may be unaw are of a
prof ound sensory loss.
Pain ref erred t o as thal ami c pai n is perhaps t he best know n component of
Dejerine and Roussy t halamic syndrome, described earlier[114, 198] . The
unpleasant or excruciat ingly painf ul sensat ion on t he side of t he body
cont ralat eral t o a t halamic lesion (an inf arct is most common) may appear at t he
t ime of t he injury[48] or w hen t he sensory loss begins t o improve. The pain f eels
localized t o t he skin. Cut aneous st imuli t rigger paroxysmal exacerbat ions of t he
pain, w hich persist s af t er t he st imulus has been removed. The lat ency bet w een
t he st imulus and pain percept ion is prolonged, suggest ing t hat t he pat hw ays
conveying it are polysynapt ic. Because t he percept ion of epicrit ic pain, such as
t hat induced w it h a pin-prick, is reduced on t he painf ul areas, t his sympt om has
been t ermed anesthesi a dol orosa, or painf ul anest hesia. A similar sympt om may
f ollow damage of t he post erior root ganglia (herpes zost er) or t rigeminal nerve
or nucleus (t rigeminal neuralgia w it h anest hesia). Vent ropost erior t halamic
nuclear lesions are more likely t o produce half -body pain t han lesions elsew here
in t he sensory pat hw ays[16] . Some pat ient s w it h chronic localized neuropat ic
pain can be relieved by st imulat ion of t he basal vent ropost eromedial region of
t he t halamus. Met abolic st udies in such a pat ient show ed t hat pain relief
correlat ed w it h increased met abolic rat es in pref ront al and ant erior insular
cort ices, hypot halamus, and periaqueduct al gray, all of t hem st ruct ures t hought
t o play an import ant role in pain percept ion[91] .
Thalamic pain seldom occurs w it h t umors. I t has been described most of t en w it h
vascular lesions, some of w hich involve not only t he t halamus but also t he deep
pariet al w hit e mat t er[2] . Besides, delayed pain may f ollow cort ical pariet al
inf arct s, part icularly t hose in t he bank of t he Sylvian f issure, aff ect ing t he
second somat osensory area (pseudot halamic syndrome)[ 9, 159] .
Loss of Sensory M odalities

All somat osensory modalit ies are processed in t he vent ral post erior nucleus of
t he t halamus cont ralat eral t o t he side of t he body w here t hey are perceived.
Wit hin t he nucleus t here is a def init e t opographic dist ribut ion: t he head is
represent ed ant eroinf eromedially, w hereas t he leg is represent ed
post erosuperolat erally; t he arm is represent ed in an int ermediat e posit ion. A
larger volume of t he nucleus is dedicat ed t o t he mout h, t ongue, and dist al port ion
of t he ext remit ies; t heir t halamic represent at ion is almost complet ely crossed.
The large oral t halamic and cort ical represent at ion in humans may w ell be
relat ed t o language f unct ions[26] . The f ace, proximal port ion of t he limbs, and
t runk are represent ed in a smaller volume of t halamic t issue, mainly cont ralat eral
but part ially ipsilat eral[17] . Thalamic sensory loss t ends t o occur maximally in
t he dist al port ion of t he limbs and of t en spares t he f ace[86] . Such sparing may
be relat ed t o t he diff erent vascular supply of t his port ion of t he vent ropost erior
region (paramedian t errit ory) or t o t he bilat eral t halamic represent at ion of t he
f ace.
I n regard t o t he t halamic t opography of various sensory modalit ies, physiologic
experiment al st udies have show n t hat cells concerned w it h deep pressure and
movement s of t he limbs are pref erent ially locat ed in t he rost ral and caudal ends
of t he vent ral post erior lat eral nucleus. The cent ral part of t he nucleus cont ains
neurons t hat respond t o cut aneous st imuli. I n humans, how ever, lesions large
enough t o produce any sensory loss most of t en involve several modalit ies. No
exist ent clinicopat hologic st udies allow precise ident if icat ion of t halamic areas
f or t ouch versus joint posit ion or vibrat ion. Pain sensat ion has been obt ained by
st imulat ion of t he basal part of t he nucleus[17] .
Because t he percept ion of pin-prick, t emperat ure, t ouch, or vibrat ion is alt ered
more of t en af t er t halamic t han af t er cort ical lesions, t hese sensory modalit ies
have been t ermed pri mary or thal ami c. By cont rast , conscious joint posit ion
ident if icat ion, t w o-point discriminat ion, st ereognosis, and graphest hesia t end t o
be more impaired af t er cort ical pariet al lesions, and are t heref ore t ermed
secondary or corti cal sensory modalit ies. Nevert heless, pariet al lesions of t en
cause some impairment of t halamic modalit ies and vice versa. O ccasionally, a
lesion in t he t halamus may dist urb mainly t he so-called cort ical sensory
modalit ies[ 51, 193] .
Anest hesia and impaired temperature percept ion t end t o occur w it h basal lesions
near t he medial geniculat e body[16, 17] . Because vi brati on sense remains
unalt ered af t er surgical removal of t he pariet al cort ex, it has been assumed t hat
hemispheric lesions causing loss of vibrat ory sense necessarily implicat e t he
t halamus or t he t halamocort ical project ions[155] .
Decreased t halamic perf usion has been observed w it h hyst erical hemisensory
loss[ 191] . This abnormalit y revert ed w hen t he pat ient s improved.
Dist urbances of vi si on and heari ng are discussed in Chapt ers 7. Visual f ield
def ect s caused by t halamic lesions f requent ly involve t he superior quadrant
bilat erally. An int olerance t o light (“cent ral dazzle”) has been ascribed t o a
t halamic lesion[38, 42] . Paramedian t halamic inf arct ion may cause t he sudden
onset of vivid, f ormed visual hallucinat ions (suggest ing peduncular hallucinosis)
associat ed w it h agit at ion and sleep dist urbance (MRI revealed no abnormalit y of
t he midbrain or cerebral peduncles)[ 46] . Vivid visual hallucinat ions, suggest ing
peduncular hallucinosis, w it h lef t hemiparesis and lef t parest hesias have been
described w it h a right post erior t halamic inf arct [165] . Audit ory and visual
experient ial hallucinat ions may occur w it h unilat eral t halamic lesions aff ect ing t he
int ralaminar and dorsomedial nuclei[107, 135] . Audit ory illusions of hyperacusis
and palinacousis may occur w it h a lesion in t he medial geniculat e body[52] .
Unilat eral visual sensory neglect may occur w it h lesions of t he right pulvinar[83,
183] .
A dist urbance of olf act ory and gust at ory percept ion w as not ed in a pat ient w it h
bilat eral dorsomedial and int ralaminar t halamic lesions. O dors and t ast e w ere
perceived eit her in a neut ral w ay, t heir pleasant charact er having disappeared,
or as unpleasant [156] . Tast e sensat ions have been elicit ed in humans by
st imulat ion of a port ion of t he vent ropost eromedial nucleus[97] .
Motor Disturbances
Just as t he sensory dist urbances described in t he previous sect ion can be
relat ed t o lesions in t he vent ral post erior nucleus of t he t halamus, mot or
dist urbances can be relat ed t o lesions of t he vent ral lat eral nucleus and t he
adjacent subt halamic region.
Postural Disturbances
Follow ing an acut e t halamic lesion, even a unilat eral lesion, pat ient s may be
t ransient ly unable t o st and or even sit , despit e normal st rengt h of t he limbs w hen
t est ed against resist ance (thal ami c astasi a) [ 110, 111, 186] . The lesions,
including inf arct ion, hemorrhage, or t umor, primarily involved t he
superopost erolat eral t halamus and
spared t he rubral region. Alt hough alert , w it h normal or near-normal st rengt h and
a variable degree of sensory loss, pat ient s w it h t halamic ast asia cannot st and,
and of t en cannot even sit up unassist ed. They f all backw ard or t ow ard t he side
cont ralat eral t o t he lesion and appear t o have a def icit of overlearned mot or
act ivit y of an axial and post ural nat ure[110] . Sudden f alling t o one side w hile
sit t ing, st anding, or w alking has also been described w it h basal ganglia lesions
cont ralat eral t o t he side of t he f all[92] . Some pat ient s w it h post erolat eral
t halamic lesions push act ively t o t he side cont ralat eral t o t he lesion (pusher
syndrome)[ 84] . The post ural dist urbance of t halamic lesions may be
accompanied by a dist urbance in t he pat ient 's percept ion of t he vert ical axis [39,
40, 82] .
Post ural abnormalit ies in pat ient s w it h lesions in t he vent rolat eral nucleus or it s
connect ions w it h t he medial f ront al region, in t he suprat halamic w hit e mat t er, go
beyond simple disequilibrium[110, 111] . Volit ional movement s, like t rying t o
overcome t he st rengt h of t he examiner during isomet ric t est ing, are normal. Yet
t he pat ient does not use t he same st rong limbs, and part icularly t he axial
muscles, in t asks t hat are normally perf ormed aut omat ically or w it hout much
t hinking, such as shif t ing in bed. Proximal movement s t hat normally support dist al
ones, such as abduct ion of t he shoulder w hen t rying t o pick up a cup, are
rest rict ed, even t hough t he pat ient is perf ect ly able t o abduct his or her shoulder
on command. This syndrome occurs w it h lesions of eit her t halamus and is
diff erent f rom t he sensory hemineglect described predominant ly w it h
nondominant t halamic lesions[83, 110] . I t has been called motor negl ect[ 106] .
Negl ect t o use t he limbs cont ralat eral t o t he lesion may convey t o t he examiner
t he f alse impression t hat t he pat ient is hemiplegic [6, 12, 14, 141, 194, 195] .
Cert ainly large inf arct s, lacunes[126] , hemat omas[193] , and t umors may involve
t he neighboring int ernal capsule, causing a more or less prof ound hemiplegia.
How ever, purely t halamic involvement does not result in hemiparesis. Lesions in
t he vent ral lat eral nucleus of t he t halamus cause cont ralat eral hypot onia,
reduct ion of emot ional expression, and t ransient neglect [70, 106] . This syndrome
may occur even w it h lesions t hat are discret e enough t o spare all sensory
modalit ies and t he early (t halamic) component s of t he somat osensory evoked
response. Such lesions, w hich are circumscribed t o t he vent ral lat eral nucleus,
spare t he vent ral post erior nucleus. Because t he lat e component s of t he
somat osensory evoked response are abolished, it has been post ulat ed t hat t he
vent ral lat eral nucleus plays a key role in t he act ivat ion of t he f ront al cort ex.
Unilat eral t halamic lesions cause aki nesi a, eit her as a result of sensory
inat t ent ion or as a consequence of impaired act ivat ion of axial, aut omat ic
synergies, as described earlier [14, 111, 186, 195] .
Other M otor Disturbances

Lesions of t he t halamus may cause emot ional f acial paresis (i. e. , w eakness of
emot ionally evoked f acial movement s, such as smiling, w it h normal volit ional
act ivat ion)[ 73] . Cont ralat eral emot ional f acial paresis has been described w it h
lesions of t he t halamus and subt halamus, ant erolat eral t halamus and insula,
post erior t halamus and operculum, and post erior t halamus [13, 14, 62, 73] .
Damage t o t he dent at orubrot halamic project ion t o t he vent ral lat eral nucleus by a
lesion rost ral t o t he decussat ion of t he superior cerebellar peduncle or damage
t o t he vent ral lat eral nucleus it self result s in hemi ataxi a (coarse, w it h act ion
t remor, dysmet ria, dysdiadochokinesia, and rebound) of t he cont ralat eral
limbs[ 108] . These st ruct ures are near t he cort icospinal pat hw ays and t he vent ral
post erior nucleus of t he t halamus, explaining w hy t he hemiat axia is associat ed
w it h hemiparesis or hypest hesia in t his t ype of inf arct [119] . I solat ed hemiat axia
and ipsilat eral sensory loss (t he hemiat axia-hypest hesia syndrome) may be a
manif est at ion of t halamic inf arct ion in t he t halamogeniculat e t errit ory causing
damage t o t he vent ral post erior nucleus and vent ral lat eral nucleus[118] . The
cerebellar syndrome is not as severe as w it h t he involvement of t he superior
cerebellar peduncle or dent at e nucleus. Regarding hand movement s, pinching
may be involved in bot h cases, but reaching t ends t o be spared w it h t halamic
lesions[ 8] . Some w eeks af t er t he injury (w hich is most of t en ischemic), tremor at
a rat e of bet w een 3 and 5 cycles per second may appear in t he aff ect ed
ext remit ies[ 124] . I t is mainly dist al and increases great ly during t he perf ormance
of any movement . This t remor may be abolished by st imulat ion or by a surgical
lesion of t he vent ral lat eral nucleus of t he t halamus[162] . I f t he cent ral t egment al
t ract is also involved, a t remor w it h a similar rat e may aff ect t he eyelids, eyes,
or palat e (“palat al myoclonus or t remor”). Such ischemic lesions occupy t he
t errit ory of t he t halamopeduncular paramedian vessels and are of t en relat ed t o
occlusion of t he t op of t he basilar art ery[24] . Cont ralat eral cerebellar at axia and
propriocept ive sensory loss may occur w it h lesions of t he vent ropost erior
t halamus, likely due t o int errupt ion of cerebellar out f low pat hw ays in t he
t halamus rat her t han t o sensory deaff erent at ion[66] .
Lesions t hat are slight ly more rost ral, involving t he subt halamic region and t he
pallidot halamic project ions t o t he vent ral lat eral nucleus, may cause t ransient
cont ralat eral hemi bal l i smus[ 90] . Af t er some days or w eeks, t he amplit ude of t he
movement decreases and eit her disappears or adopt s a choreic or at het ot ic
pat t ern.
Dystoni a may be secondary t o a necrot izing lesion or t o degenerat ion, as w it h
t he f amilial dyst onias. Messenger ribonuclenic acid (RNA) f or t orsinA, a prot ein
encoded by t he gene abnormal in early onset t orsion dyst onia, is abundant ly
present in t he t halamus[4] . Thalamic inf arct s in t he int ermediat e and caudal
port ions of t he vent rolat eral nucleus may cause myoclonic dyst onia in t he
cont ralat eral limbs [54, 89, 95, 99] . The myoclonic nat ure of t he def icit , of t en
accompanied by act ion t remor or chorea, diff ers f rom t he dyst onia w it h t onic
spasms more charact erist ic of st riat opallidal lesions[89, 95] . The onset of t he
dyst onic movement s of t en lags by mont hs or years af t er t he acut e insult [54, 56] .
Dyst onic t remor w it h chronic MRI evidence of inf arct ion in t he ant erior nucleus of
t he t halamus may have result ed f rom a more post erovent ral lesion causing
at rophy but no cavit ary lesions in t he involved nuclei[30] . The sensory f ields of
t halamic neurons is enlarged in pat ient s w it h dyst onia[96, 98] . Pat ient s w it h
secondary dyst onia or hemiballismus of basal ganglionic origin t end t o improve
w it h lesions or st imulat ion of t he vent rolat eral nucleus of t he t halamus[22] .
Abnormal post uring of t he hand, of t en t ermed thal ami c hand, may appear 2 or
more w eeks af t er t he occurrence of a vascular lesion of t he same region. The
hand assumes a post ure w it h f lexion at t he w rist and met acarpophalangeal
joint s, w hereas t he int erphalangeal joint s are hyperext ended. Flexion of t he
met acarpophalangeal joint s increases f rom t he second digit , w hich may act ually
be ext ended, t o t he f if t h digit , w hich is markedly f lexed. The f ingers may be
f orcibly abduct ed. The t humb is eit her abduct ed or pushed against t he
palm[ 109] .
O t her abnormal movement s described w it h t halamic lesions include act ion
myocl onus[ 5] , ideomot or apraxi a[ 132] , and asteri xi s [ 18, 41, 110, 172] .
Ast erixis is more common w it h vent rolat eral nucleus lesions[176] . Hyperekplexia,
t he sudden loss of post ural t one caused by st art ling st imuli, may be exacerbat ed
w it h t halamic lesions [45] . Imi tati on synki neses, also called mi rror movement s,
are common af t er t halamic lesions [112] . I n such cases, t he dist al port ion of t he
limb cont ralat eral t o t he t halamic lesion t ends t o imit at e t he movement
perf ormed by t he healt hy side. When t he pat ient f orcibly makes a f ist w it h t he
sound hand, t he f ingers of t he ot her hand curl up int o t he palm, and t he pat ient
ends by making a f ist w it h bot h hands. Loss of posit ion sense or loss of cort ical
act ivat ion by t he t halamus may underlie t hese abnormal movement s, w hich can
be decreased, like t he choreic movement s described earlier, w hen t he pat ient
concent rat es his at t ent ion on avoiding t hem.
A decreased corneal ref lex may be present in pat ient s w it h hemiparesis and
hemisensory loss due t o a cerebral hemispheric lesion[47] . Loss of pariet al
excit at ory inf luence on t he low er brainst em seems t o be responsible f or t his
f inding[ 137] . Pure t halamic lesions, even t hose t hat cause a marked hemisensory
loss, do not depress t he corneal ref lex[138] . How ever, a pat ient w it h an acut e
t halamocapsular lesion had bilat erally depressed lat e component s of t he blink
ref lex w hen t he side cont ralat eral t o t he lesion w as st imulat ed[29] . I t is possible
t hat t he damage of cort ico-pont ine f ibers t raveling in t he int ernal capsule may be
responsible f or t he def icit .
Small surgical lesions or chronic st imulat ion of t he vent rolat eral nucleus of t he
t halamus may ameliorat e drug-resist ant t remor[162] .
Disturbances of Ocular Motility

Lesions rest rict ed t o t he t halamus cause only subt le changes in ocular mot ilit y.
Visual inf ormat ion f rom t he superior colliculus, relayed by t he pulvinar t o t he
pariet al lobe (“second visual syst em”), cont ribut es t o t he det ect ion and
localizat ion of visual event s in space and t o t he product ion of saccadic eye
movement s t hat allow t he “f irst ” (geniculost riat e) visual syst em t o ident if y such
event s. Lesions in t he pulvinar have been said t o cause (a) a decrease in t he
crit ical f licker f requency and neglect of visual object s in t he periphery of t he
cont ralat eral visual f ield, (b) prolonged lat ency of visually evoked saccadic eye
movement s, and (c) a paucit y of spont aneous eye movement s direct ed t ow ard
t he cont ralat eral hemif ield[201] .
Much more st riking, and more obvious at t he bedside, are eye movement
abnormalit ies t hat occur w hen a lesion involves t he midbrain and t halamus; t his
of t en happens w it h paramedian t halamopeduncular inf arct s[24] . I n such cases,
impairment of ocular mot or f unct ion result s in abnormal pupils, pt osis, and
rest rict ion of vert ical eye movement s and of adduct ion. Select ive upgaze,
dow ngaze, or combined dysf unct ion may occur[14] , as may blepharospasm[149] ,
bilat eral int ernuclear opht halmoplegia w it h pt osis[14] , and pseudo-sixt h nerve
palsy[ 19] (see Chapt er 7).
Thalamic lesions may be associat ed w it h vert ical gaze palsies not due t o
t halamic injury per se but due t o ext ension of t he lesions int o t he upper
midbrain[ 168] . A “vert ical one-and-a-half syndrome” (vert ical palsy in one eye,
upw ard palsy in t he ot her eye) may occur [13, 14, 175] . Bilat eral medial t halamic
lesions may cause purely vert ical saccadic apraxia, aff ect ing volit ional vert ical
but not random saccades[123] . Acute thal ami c esotropi a, w it h impaired upw ard
gaze, has been described w it h inf arct ion of t he cont ralat eral post erior t halamus
in t he basilar-communicat ing art ery t errit ory[58] . Tonic act ivat ion of t he medial
rect us in t his case could result f rom damage t o direct inhibit ory project ions f rom
t he t halamus or impairment of input s t o midbrain neurons involved w it h vergence
cont rol[ 58] .
Large t halamic hemorrhages may impinge on t he midbrain or impair it s f unct ion
by causing raised int racranial pressure[57] . The eyes t hen become t onically
deviat ed dow n and slight ly adduct ed, as if peering at t he t ip of t he nose[193] . I n
some inst ances, t he eyes may be t onically deviat ed t o t he side of t he
hemiparesis, opposit e a t halamic hemorrhage (“w rong-w ay eyes”)[ 50, 180] . This
f inding has also been report ed in ext rat halamic suprat ent orial lesions[146, 180] .
DBS f or t he t reat ment of epilepsy, w it h elect rodes placed at t he
mesodiencephalic junct ion, just inf erior t o t he cent romedian nucleus of t he
t halamus, may cause nyst agmus w it h const ant velocit y slow phases, beat ing t o
t he right w hen t he lef t t halamus is st imulat ed and vice versa[177] .
Depression of t he ret icular act ivat ing syst em (most of t en met abolic in nat ure) or
involvement of bot h t halami result s in small pupils (1 mm in diamet er) t hat react
w ell t o light (diencephalic pupils) [147] . Anisocoria is occasionally present , w it h
t he smaller pupil ipsilat eral t o t he t halamic lesion.
Disturbances of Complex Sensorimotor Functions

The t halamus modulat es t he associat ion cort ex involved in t he processing of
language and ot her “higher” cort ical f unct ions. Alt hough compared w it h large
cort ical lesions, unilat eral t halamic lesions do not impair t hese f unct ions as
much; t he pat t ern of impairment has some localizing value. Ment ion has already
been made of t he cont ralat eral mot or neglect caused by lesions in t he vent ral
lat eral nucleus of t he t halamus and t he cont ralat eral visual inat t ent ion t hat
result s f rom lesions in t he pulvinar.
Pat ient s w it h right t halamic lesions may have const ruct ional apraxia and display
marked neglect of t he lef t hemif ield[194, 195] . This hemineglect may be
associat ed w it h anosognosia and asomat ognosia, t hereby mimicking a pariet al
lobe lesion[12, 194] , and is likely due t o damage t o t he int ralaminar and
vent rolat eral nuclei on t he right [195] . Right t halamic lesions can also cause
impairment in t he ident if icat ion of emot ional f acial expressions w it h preserved
discriminat ion of f acial ident it y (prosopoaff ect ive agnosia)[ 192] . Alexia relat ed t o
impaired visuospat ial percept ion has been described af t er right t halamo-occipit al
inf arct ion[ 71] . O pt ic at axia or visuomot or apraxia has been described in a pat ient
w it h CT evidence of bilat eral lesions in t he pulvinar, t he one on t he lef t in t he
acut e st age w hen t he pat ient w as st udied[33] .
Dominant -hemisphere t halamic lesions may cause a transi ent language
dist urbance (t halamic aphasia) [14, 60, 75, 182] charact erized by (a) reduced
spont aneous speech w it h paraphasic errors and perseverat ion, (b) varying
degrees of audit ory comprehension impairment , (c) preserved repet it ion and
reading, (d) def ect ive spont aneous w rit ing and w rit ing t o dict at ion but normal
copying, (e) w ord-product ion anomia but spared w ord select ion and w ord
symbolism, and (f ) dist ract ibilit y. This def icit , w hich w ould be classif ied as a
mixed t ranscort ical aphasia, t ends t o improve in a f ew w eeks [3, 21, 75] . The
language def icit may have more semant ic component s w hen t he lesion is
post erior[ 152] and more mot or component s w hen t he lesion aff ect s t he ant erior
nucleus[ 55] . Elect rical st imulat ion of t he vent rolat eral t halamus produces an
accelerat ion of speaking. The pat ient f eels urged t o speak f ast er[70] .
St imulat ion also enhances lat er recall of object s present ed t o t he pat ient . The
lef t t halamus is involved in at t ent ion mechanisms t hat gat e st orage and ret rieval
of bot h long-t erm and short -t erm verbal memory[76] . Derangement of a specif ic
cort ical at t ent ion mechanism because of t he t halamic lesion result s in a lack of
drive t o speak and perseverat ion of apparent ly unrelat ed verbal mat erial[154] .
Some pat ient s have hypophonia and dysart hria[55] . Such language impairment
resembles t he one t hat result s f rom lef t medial f ront al lesions[15, 113] . O t her
dorsomedial t halamic lesions cause a bizarre language pat t ern, w it h some
charact erist ics of dysf unct ion in t he pref ront al cort ex. I t cont ains int rusions
(segment s of speech out of cont ext ) and ot her evidence of t emporal gat ing
impairment , such as giving biographical inf ormat ion w hile w orking on a
calculat ion t est [28, 55] . Apraxic agraphia has been described w it h an MRI
show ing a dorsomedial t halamic lesion[136] .
The language impairment not ed w it h lef t t halamic lesions and t he visual neglect
not ed w it h right t halamic lesions are associat ed w it h decreased act ivit y of
ipsilat eral f ront al or t emporopariet al associat ion cort ex [6, 122, 136, 141] .
Deaff erent at ion of an ot herw ise int act cort ex (diaschisis) due t o t he t halamic
lesion may explain t hese “cort ical” syndromes w it h t halamic lesions. For
example, t halamic aphasia may be due t o decreased cort ical act ivat ion
secondary t o t he subcort ical lesion [6, 122, 141] . Some aut hors ascribe t o
t halamic lesions or t halamocort ical disconnect ion t he cases of st riat ocapsular
aphasia report ed in t he lit erat ure[131] .
A st ut t ering-like repet it ive speech disorder may occur w it h inf arct ion in t he
paramedian t halami and midbrain[1] . Alt hough t he speech disorder seems like
st ut t ering, t he compulsive repet it ions, const ant rat e, and monot onous t one seen
w it h t hese inf arct ions are not associat ed w it h ordinary st ut t ering. The repet it ive
speech disorder in pat ient s w it h inf arct s in t he supplement ary mot or area have
similar clinical f eat ures[1] .
Disturbances of Executive Function

Paramedian t halamic inf arct ion may cause a lack of init iat ive and “f ront al lobe”
ut ilizat ion behavior (see Chapt er 20), suggest ing a t halamof ront al component t o
environment al int eract ions t hat requires inhibit ion, self -monit oring, and cognit ive
f lexibilit y [43, 55, 69] . The pat ient s' language may appear bizarre because of t he
presence of int rusions (segment s of speech out of cont ext ) and t he
superimposit ion of ment al act ivit ies normally processed sequent ially, f or
inst ance, giving biographical inf ormat ion w hile w orking on a calculat ion t est [28,
55] . Failure of goal-direct ed regulat ion of behavior has been observed w it h a
lesion aff ect ing t he right ant erovent ral t halamic region[134] . A lef t -sided discret e
inf arct ion of t he medial t halamus may cause severe impairment of complex
execut ive behaviors, probably due t o dysf unct ion of t halamof ront al linkages t hat
help modulat e complex human behavior[157] . Repet it ive movement s (“clonic
perseverat ion”) may be a manif est at ion of execut ive f unct ion disorder w it h
t halamic lesions[53] .
I nf arct ion of t he dorsomedial nucleus, int ralaminar nuclei, and medial part of t he
vent rolat eral nuclei is of t en associat ed w it h marked hypoperf usion of t he
overlying f ront al region cort ex on posit ion emission t omography (PET) or single
phot on emission comput ed t omography (SPECT)[ 28, 69] . I t is t hought t hat t he
“f ront al lobe-like” syndrome w it h t halamic lesions may be relat ed t o impaired
act ivat ion of t he f ront al lobe by t he damaged dorsomedial and ant erior t halamic
nuclei[ 12, 185] . These nuclei provide an import ant pat hw ay f or t he inf ormat ion
f rom t he veget at ive cent ers t o reach t he f ront al lobe.
Topographic Localization of Thalamic Lesions

Follow ing t he det ailed and ref erenced account of t he localizat ion of t halamic
sympt oms and signs, a brief synopsis organized by t he anat omic regions of t he
t halamus f ollow s.
Anterior Thalamic Region

Discret e lesions may be silent or cause language dist urbances w hen t hey aff ect
t he dominant hemisphere. They may also cause inat t ent ion, w hich result s more
of t en w hen t he right hemisphere is involved. Bilat eral lesions may cause
akinesia, amnesia, and at t ent ional dist urbances. Lesions ext ending t o t he
subt halamic area may cause at het osis, chorea, or post ural abnormalit ies
(t halamic hand).
Medial Thalamic Region

Lesions in t his locat ion may pass unnot iced w hen t hey are small and unilat eral.
Large or bilat eral lesions cause impairment of recent memory, apat hy or
agit at ion, at t ent ion derangement s, and somnolence or coma. Lesions t hat ext end
t o t he midbrain-diencephalic junct ion may cause cont ralat eral t remor and vert ical
gaze palsy, aff ect ing part icularly dow nw ard gaze.
Ventrolateral Thalamic Region

Sensory loss, paroxysmal pains, and hemiat axia in t he cont ralat eral side of t he
body are t he most st riking sequelae of lesions in t he post erior port ion of t his
region. More ant erior lesions cause post ural abnormalit ies, such as
disequilibrium and rest rict ion of axial support ive movement s or delayed t remor.
Hemineglect and language dist urbances may appear t ransient ly.
Posterior Region
Basal lesions in t his region may cause hemianest hesia, “t halamic pain, ” and
visual f ield def ect s. Dorsal lesions give rise t o at t ent ional disorders of t he
ipsilat eral hemisphere, result ing in t ransient aphasia w hen t he dominant
hemisphere is involved. Some pat ient s may have myoclonic dyst onia.
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> Table of C ontents > C hapter 19 - B as al Ganglia
Chapter 19
Basal Ganglia
Anatomy of the Basal Ganglia

Basal gangl i a ( Fig. 19-1) include t he corpus stri atum, t he substanti a ni gra ( pars
compacta and a pars reti cul ari s), t he subthal ami c nucl eus of Luys, and t he
vent ral t egment al area. The corpus stri atum comprises t he stri atum proper (or
neostri atum), made up of t he putamen, caudate nucl eus, and nucl eus
accumbens, and t he gl obus pal l i dus (or pal eostri atum), w it h it s medial or
int ernal (G pi) and lat eral or ext ernal (G pe) segment s and t he vent ral pallidum,
w it h it s i nternal and external port ions.
The basal ganglia play a major role in t he cont rol of post ure and movement .
Marsden[ 209, 210] proposed t hat “t he basal ganglia are responsible f or t he
aut omat ic execut ion of learned mot or plans; ” t hat is, t he basal ganglia mediat e
movement s t hat have been “laid dow n by pract ice” and t hat are subconscious.
Examples of such movement s include shif t ing in bed and w alking, as w ell as t he
proximal movement s t hat support dist al ones. Someone t yping a let t er may be
conscious of t he movement s of t he f ingers on t he keyboard but is not generally
conscious of t he shoulder abduct ion and ext ension t hat allow t he f ingers t o f ly
over t he keyboard.
The major anat omic connect ions of t he basal ganglia[6, 43] are complex (Fig.
19-2) and include several “closed circuit s” of connect ions [243, 252, 257] . I n
essence, t he basal ganglia consist of an input zone, comprising t he put amen,
caudat e nucleus, and vent ral st riat um, and an out put zone, comprising t he medial
globus pallidus and t he subst ant ia nigra pars ret icularis. The main out put s f rom
t he medial globus pallidus and subst ant ia nigra pars ret iculat a are t o t he
t halamus, and t hence t o t he premot or (e. g. , supplement ary mot or area, ant erior
cingulat e mot or area, and lat eral premot or cort ex) and f ront al lobe st ruct ures.
Some of t he main connect ions are discussed in subsequent t ext .
Inputs into the Striatum (Caudate and Putamen)

Cortical Projections to the Neostriatum
All part s of t he cerebral cort ex give rise t o eff erent f ibers t o t he caudat e and
put amen. These cort icost riat e project ions t erminat e mainly ipsilat erally in a
t opographic pat t ern (e. g. , t he f ront al cort ex project s f ibers t o t he vent ral head of
t he caudat e and rost ral put amen). The cort ex also sends f ibers t o t he subst ant ia
nigra, subt halamic nucleus, and claust rum.
Thalamostriatal Projections
The int ralaminar nuclei of t he t halamus, especially t he cent rum medianum (CM)
nucleus, send f ibers t o t he st riat um.
Nigrostriatal Projections
Fibers originat ing in t he pars compact a of t he subst ant ia nigra project t o t he
st riat um (caudat e nucleus, put amen, and globus pallidus).
Raphe Nuclei-Striatal Projections

The brainst em raphe nuclei send ascending f ibers t o t he st riat um.
Striatal Efferents
Most st riat al eff erent s project t o t he globus pallidus (t o bot h t he int ernal and
ext ernal segment s). O t her st riat al eff erent s go t o t he subst ant ia nigra.
FI G URE 19-1 Anat omy of t he basal ganglia
Pallidal Afferents and Efferents

The globus pallidus receives ascending aff erent f ibers f rom t he subst ant ia nigra
and subt halamus (mainly t o t he medial or int ernal pallidum). Bot h t he ext ernal
and int ernal globus pallidus also receive aff erent s f rom t he st riat um.
The major out f low f rom t he globus pallidus arises f rom t he int ernal port ion and
project s t o t he vent ral ant erior (VA) and vent ral lat eral (VL) nuclei of t he
t halamus. These t halamic nuclei also receive aff erent s f rom t he pars ret icularis
of t he subst ant ia nigra. Because t he VL t halamic nucleus project s t o t he mot or
cort ex and t he VA t halamic nucleus project s t o t he premot or cort ex, t he major
basal ganglia eff erent s inf luence t he mot or syst em.
Eff erent s f rom t he int ernal globus pallidus also project t o t he CM t halamic nuclei,
w hich in t urn project t o t he put amen. A closed circuit is t hereby f ormed: put amen
—int ernal pallidum—cent ral medianum nucleus—put amen. The int ernal globus
pallidus also sends f ibers t o t he lat eral habenular nucleus.
The ext ernal port ion of t he pallidum sends f ibers t o t he int ernal pallidum and t o
t he subt halamic nucleus. The subt halamic nucleus in t urn sends f ibers t o bot h t he
int ernal and ext ernal pallidum. Theref ore, anot her closed circuit is f ormed:
ext ernal globus pallidus—subt halamus—ext ernal and int ernal globus pallidus.
O t her pallidal eff erent s also project t o t he subst ant ia nigra, red nucleus, inf erior
olive, hypot halamus, and mesencephalic ret icular f ormat ion.
Nigral Afferents and Efferents

The pars ret icularis of t he subst ant ia nigra receives f ibers f rom t he cerebral
cort ex, t he st riat um, t he globus pallidus, and t he subt halamic nucleus. Pars
ret icularis eff erent s project t o t he VA and VL t halamic nuclei and t o t he ret icular
f ormat ion and superior colliculus.
The pars compact a of t he subst ant ia nigra sends dopaminergic f ibers t o t he
caudat e nucleus and put amen. This out put is excit at ory f or t he st riat al neurons of
t he direct pat hw ay and inhibit ory t o t he st riat al neurons of t he indirect pat hw ay,
described in t he subsequent t ext .
I t can t hus be seen t hat t he basal ganglia exert t heir inf luence mainly by w ay of
t he cerebral cort ex (i. e. , t hey do not send f ibers t hat connect direct ly w it h
brainst em and spinal cord st ruct ures). They provide a subcort ical net w ork by
w hich t he ent ire cerebral cort ex can inf luence t he mot or syst em (mot or and
premot or cort ex), mainly by t he f ollow ing circuit : cerebral cort ex— neost riat um—
globus pallidus and subst ant ia nigra—VA and VL t halamic nuclei-mot or and
premot or cort ex.
Bot h anat omically and physiologically, a direct and an indirect syst em have been
described in t he st riat o-pallido-t halamic project ion. I n t he direct syst em, t he
put amen and t he caudat e receive excit at ory input f rom t he pars compact a of t he
subst ant ia nigra and project inhibit ory f ibers (γ-aminobut yric acid, or G ABA,
colocalized w it h subst ance P) t o t he medial globus pallidus and t o
t he pars ret icularis of t he subst ant ia nigra w hich, in t urn, inhibit t he vent rolat eral
nucleus of t he t halamus. St imulat ion of t his syst em w ould disinhibit t he
vent rolat eral nucleus of t he t halamus, result ing in cort ical excit at ion. I n t he
indirect syst em, t he put amen and caudat e receive inhibit ory input f rom t he pars
compact a of t he subst ant ia nigra and project inhibit ory f ibers (G ABA colocalized
w it h enkephalin) t o t he lat eral globus pallidus w hich, in t urn, inhibit s (t hrough
G ABA) t he subt halamic nucleus. The subt halamic nucleus st imulat es (t hrough
glut amat e) t he medial globus pallidus, inhibit ory over t he vent rolat eral nucleus of
t he t halamus. St imulat ion of t his syst em inhibit s t he vent rolat eral nucleus of t he
t halamus and result s in cort ical inhibit ion.
FI G URE 19-2 Anat omic connect ions of t he basal ganglia
I n f unct ional t erms, t he act ivit ies of t he basal ganglia pat hw ays w it hin t he
st riat opallidal mot or loop can, t heref ore, be summarized as f ollow s:
1. Cort icost riat al input f rom t he sensorimot or cort ex (glut amat e) or input f rom
t he subst ant ia nigra pars compact a (dopamine) excit e direct inhibit ory
pat hw ays of t he put amen and medial globus pallidus and subst ant ia nigra
pars ret iculat a result ing in disinhibit ion of t halamic nuclei, w hich project
excit at ory input t o t he precent ral mot or f ields. The net eff ect is f acilit at ion of
cort ically init iat ed movement .
2. Cort icost riat al st imulat ion of t he indirect syst em has a net eff ect of releasing
subt halamic input t o t he medial globus pallidus, leading
t o increased inhibit ion of t halamic nuclei and reduced t halamo-cort ical input
t o t he cent ral mot or cort ex. Dopamine nigro-st riat al input inhibit s t his indirect
pat hw ay, t hereby reducing negat ive f eedback t o t he precent ral mot or
syst em.
3. Deprivat ion of t he dopamine nigro-st riat al input reduces t he posit ive
f eedback t o t he precent ral mot or syst em t hrough t he direct st riat opallidal
syst em and increases t he negat ive f eedback t hrough t he indirect syst em.
The overall eff ect of dopamine deplet ion in t he st riat um w ould be t he
inhibit ion of t he cort ically init iat ed movement , w hereas overact ivit y of t he
dopamine in t he st riat um w ould st imulat e t he cort ically init iat ed movement .
Alt hough helpf ul in concept ualizing most of t he anat omo-physiologic dat a

regarding t he connect ivit y of t he basal ganglia, t his current ly accept ed schema
does not explain some clinical f indings in basal ganglia diseases[212] .
Lesions of the Basal Ganglia

Pat hologic processes aff ect ing t he basal ganglia are of t en diff use. When
discret e, t hey usually also aff ect neighboring st ruct ures, such as t he int ernal
capsule, t he hypot halamus, and t he w hit e mat t er of t he cerebral hemispheres.
Theref ore, except f or hemiballismus of t en associat ed w it h damage t o t he
cont ralat eral subt halamic nucleus, correlat ion bet w een basal ganglia lesions and
clinical mot or dysf unct ion t ends t o be obscure.
The lit erat ure concerning behavioral eff ect s of lesions of t he basal ganglia in
experiment al animals is of t en conf lict ing, and t hese lesions rarely produce
models of human movement disorders. Theref ore, t hese st udies are not
review ed. I n general, st imulat ion and dest ruct ive lesions of t he caudat e,
put amen, and globus pallidus produce inhibit ion of movement or cont ralat eral
body t urning [220] .
Some disorders in humans associat ed w it h lesions of t he basal ganglia are as
f ollow s:
1. Lesions of t he subthal ami c nucl eus produce cont ralat eral hemiballismus[54] .
2. Small unilat eral lesions of t he ant erovent ral port ion of t he caudate cause
cont ralat eral choreoat het osis[192] .
3. Unilat eral lesions of t he globus pallidus may cause cont ralat eral
hemidyst onia, hemiparkinsonism, or t remor, w hereas bilat eral globus pallidus
lesions may cause dyst onia, parkinsonism, abulia, or akinesia[233] .
4. Lesions of t he subst ant ia nigra result in parkinsonism.
5. Unilat eral basal ganglia (pallidal-put aminal) hemorrhages or lacunar inf arct s
may present w it h sudden f alling t o t he cont ralat eral side w hile sit t ing,
st anding, or w alking[182] . The f alls are dist inct ly slow, t ilt ing mot ions in a
st ereot yped lat eral or diagonal t raject ory (“like a f alling log”) and occur w it h
t he eyes open but are exacerbat ed by eye closure.
I n a st udy of behavioral and movement disorders w it h lesions aff ect ing t he basal
ganglia, lesions of t he caudat e nucleus rarely caused mot or disorders (e. g. ,
chorea or dyst onia) but w ere more likely t o cause behavioral problems,
especially abulia (apat hy w it h loss of init iat ive and of spont aneous t hought and
emot ional responses) or disinhibit ion[33] . Lesions of t he put amen and globus
pallidus rarely caused abulia and did not produce disinhibit ion but commonly
caused dyst onia, part icularly w hen t he put amen w as involved. Bilat eral lesions of
eit her t he put amen or t he globus pallidus caused parkinsonism or dyst onia-
parkinsonism inf requent ly. The prominence of behavioral dist urbances w it h
caudat e lesions emphasizes t he more complex cognit ive role of t his st ruct ure,
w hereas t he f requent occurrence of dyst onia and less commonly parkinsonism
w it h lesions of t he put amen and globus pallidus emphasizes t he mot or roles of
t hese st ruct ures[33] . I n anot her st udy of pat ient s w it h lent icular inf arct s, t w o
dist inct clinical syndromes corresponding t o t he t w o anat omical areas of t he
lent icular nucleus w ere described[124] . I nf arct s w it hin t he globus pallidus w ere
associat ed w it h behavioral and cognit ive disorders, w hereas inf arct s in t he
put amen caused mot or disorders (dyst onia) and cognit ive impairment . Also,
damage t o a f ront al-caudat e f unct ional syst em likely underlies t he aphasias
(language dist urbances) result ing f rom subcort ical lesions aff ect ing t he deep
f ront al and paravent ricular w hit e mat t er (subcort ical aphasias)[ 226] .
Movement disorders can be def ined as neurologic dysf unct ions in w hich t here is
eit her an excess of movement Abnormal I nvolunt ary Movement s, or AI Ms;
hyperkinesias; dyskinesias) or a paucit y of volunt ary and aut omat ic movement s
(akinesia, bradykinesia, or hypokinesia) unassociat ed w it h w eakness or
spast icit y. Paucit y of movement charact erizes t he disorder know n as
parki nsoni sm. The dyskinesias are discussed f irst .
Dyskinesias
Chorea
Chorea[ 96, 283] is charact erized by sudden, brief , spont aneous, involunt ary,
purposeless, cont inuous,
irregular, and unpredict able jerks t hat randomly involve t he appendicular, f acial,
or t runcal musculat ure. The muscles involved vary depending on t he underlying
disease process (e. g. , t runcal involvement predominat es in Hunt ingt on's chorea
and dist al appendicular involvement is predominant in Sydenham's chorea). The
hyperkinet ic movement s may be unilat eral (hemi chorea) or bilat eral, occur at
rest or during volit ional act s, int erf ere w it h act ivit ies of daily living, cease during
sleep, int ensif y during st ress, and are of t en camouf laged by t he pat ient t hrough
a superimposed purposef ul act (parakinesia).
Chorea is of t en associat ed w it h changing muscle t one (e. g. , hypot onia in
Sydenham's chorea, rigidit y and hypokinesis in t he West phal variant of
Hunt ingt on's disease, and dyst onia in t he juvenile variant of Hunt ingt on's
disease). Pat ient s w it h chorea t end t o hyperpronat e t he upper ext remit y w hen
at t empt ing t o maint ain an ext ended post ure, and t hey are of t en unable t o sust ain
a t ight handgrip (mi l kmai d's gri p). The t ongue cannot be maint ained in a
prot ruded posit ion and dart s in and out irregularly (trombone or f l ycatcher
tongue). Facial grimacing and abnormal respirat ory sounds may be
manif est at ions of chorea.
Hunti ngton's di sease is an aut osomal dominant disorder w it h t he def ect localized
t o t he short arm of chromosome 4. The mut ant gene cont ains an expansion of
CAG t rinucleot ide repeat s t hat code f or a prot ein hunti ngti n. The longer t he
repeat lengt h (normal is 10–29 copies), t he earlier t he onset of t he disease.
Sympt oms of t en begin insidiously in t he t hird t hrough t he f if t h decades and are
charact erized by progressive chorea, dyst onia, eye movement abnormalit ies,
behavioral changes, and progressive dement ia. The choreat ic movement s may
ant edat e or f ollow t he dement ia. Saccadic eye movement s become slow and
uncoordinat ed, and smoot h pursuit eye movement s are f requent ly disrupt ed by
saccadic int rusions. An increased rat e of suicide has been report ed in pat ient s
w it h Hunt ingt on's disease. Hunti ngton's di sease-l i ke 2 (HDL2) is a progressive
aut osomal dominant disease w it h marked clinical and pat hologic similarit y t o
Hunt ingt on's disease[207, 306] . The gene def ect is a CTG / CAG expansion in a
variably spliced exon of t he junct ophilin-3 gene. HDL2 can present w it h
acant hocyt osis, w eight loss, and incoordinat ion usually in t he f ourt h decade.
Pat ient s may develop dyst onia, chorea, rigidit y, dysart hria, hyperref lexia,
bradykinesia, t remor, psychiat ric sympt oms, and dement ia. O t her examples of
aut osomal dominant disorders associat ed w it h chorea include benign heredit ary
chorea (BHC) (onset in childhood), Spinocerebellar At axia 3 (SCA 3 or Machado-
Joseph disease), and dent at orubropallidoluysian at rophy (DRPLA).
BHC is an aut osomal dominant disorder of t en present ing w it h childhood-onset
chorea, no dement ia, and lit t le or no progression[103, 166] . I n some pat ient s
w it h inf ancy-onset BHC, t reat ment w it h levodopa improves gait abnormalit ies and
chorea[ 17] . Anot her heredit ary (aut osomal recessive) cause of chorea is f amilial
degenerat ion of t he basal ganglia w it h acant hocyt osis[35] . Less common causes
of heredit ary chorea include Wilson's disease, Lesch-Nyhan syndrome, dopa-
responsive dyst onia (Segaw a syndrome), Niemann-Pick disease, Pelizeus-
Merzbacher disease (sudanophilic leukodyst rophy), Hallervorden-Spat z disease
(Pant ot henat e Kinase-Associat ed Neurodegenerat ion or PKAN), at axia
t elangiect asia, Leigh's disease (subacut e necrot izing encephalomyelopat hy),
t uberous sclerosis, mit ochondrial encephalopat hies, glut aric academia t ype 1,
G M1 and GM2 gangliosidoses, neuroacant hocyt osis, neurof errit inopat hy, and t he
heredit ary f orms of paroxysmal choreoat het osis.
Neuroacanthocytosi s (chorea-acanthocytosi s) is a f amilial or nonf amilial
mult isyst em progressive disorder in w hich chorea occurs in almost all cases[35,
134] . The mean age of onset is 32 years (range 8–62 years) and pat ient s
demonst rat e acant hocyt osis w it h normal lipoprot eins. I nit ial lip and t ongue bit ing
are f ollow ed by orolingual “eat ing” dyst onia, mot or and phonic t ics, generalized
chorea, akinet ic-rigid f eat ures, vert ical opht halmoparesis, and seizures. The
orof acial-lingual involunt ary dyst onic movement s and pseudo-bulbar dist urbance
commonly cause dysphagia and dysart hria. Cognit ive impairment , psychiat ric
f eat ures, and organic personalit y changes are common. O t her signs and
sympt oms include amyot rophy, axonal neuropat hy, decreased or absent muscle
st ret ch ref lexes, and increased serum creat ine kinase (CK) w it hout
myopat hy[ 134] . The abnormal gene f ound in neuroacant hocyt osis, on
chromosome 9, is an evolut ionarily conserved prot ein called chorei n t hat is
probably involved in prot ein sort ing. Chorea may also be associat ed w it h
neurogenic at rophy in cases of Fot opoulos syndrome[251] .
Neurof erri ti nopathy is a dominant ly inherit ed movement disorder caused by
mut at ion of t he f errit in light chain gene[71, 230] . Pat ient s may have low serum
f errit in levels and brain hist ochemist ry show s abnormal aggregat es of f errit in and
iron. Pat ient s w it h t his disorder present w it h variable sympt oms, beginning in t he
t hird t o sixt h decade, including chorea, dyst onia, or an akinet ic-rigid syndrome.
DRPLA is an aut osomal dominant disorder charact erized by chorea
(choreoat het osis), at axia,
dement ia, seizures, myoclonus, and dyst onia [48, 171, 308] . The disorder is
part icularly prevalent in Japan. A possibly similar disorder has been described in
t he sout hern Unit ed St at es as t he “Haw River” syndrome. The usual age of onset
is t he f ourt h decade (range, f irst t o sevent h decade). An early onset subt ype
present s w it h a variable combinat ion of myoclonus, epilepsy, and ment al
ret ardat ion, w hereas a lat e-onset subt ype is charact erized by choreoat het osis,
cerebellar at axia, dyst onia, rest and post ural t remor, parkinsonism, and
dement ia. Pat hologically pat ient s demonst rat e degenerat ion aff ect ing t he
dent at orubral syst em, globus pallidus, subt halamus, and, t o a lesser ext ent , t he
st riat um, subst ant ia nigra, inf erior olive, and t he t halamus.
Fami l i al Dyski nesi a and Faci al Myokymi a (FDFM) is a disorder t hat has an early
childhood or adolescent onset and is charact erized by advent it ious movement s
t hat somet imes appear choreif orm and t hat are associat ed w it h perioral and
periorbit al myokymia[104] . The involunt ary movement s are paroxysmal at early
age, increase in f requency and severit y, and may become const ant by t he t hird
decade. Thereaf t er, t here is no f urt her det eriorat ion and t here may even be
improvement in old age. Alt hough t his f amilial ent it y may be conf used w it h
Hunt ingt on's disease, t here is no int ellect ual impairment and t he lif espan is
normal.
Sydenham's chorea (rheumat ic chorea or St Vit us' dance), relat ed t o group A
bet a-hemolyt ic st rept ococcal inf ect ion, occurs in childhood and adolescence.
Sydenham's chorea is predominant ly or exclusively unilat eral (hemichorea) in
about half of t he cases, and it may result in an apparent f laccid paralysis
(chorea mollis). HI V encephalit is may be a cause of chorea[116, 237] as may
t uberculous meningit is. Chorea may also be caused by medicat ions (e. g. , L-
dopa, neurolept ics, met oclopramide, ant iconvulsant s, propof ol, pemoline,
cort icost eroids, lit hium, digoxin) and drugs of abuse (e. g. , cocaine-induced
choreoat het osis or “crack dancing”[76] ; amphet amines). Chorea may be
associat ed w it h a variet y of syst emic disorders (e. g. , syst emic lupus
eryt hemat osus, Henoch-Schönlein purpura, sarcoidosis, vasculit is, mult iple
sclerosis, Behçet 's disease, hypert hyroidism, Hashimot o's encephalopat hy,
hypoparat hyroidism, acquired hepat ocerebral degenerat ion, renal f ailure,
polycyt hemia vera, hypo- or hypercalcemia, hypo- or hypernat remia, hypo- or
hyperglycemia, mercury poisoning, carbon monoxide poisoning), and may also
occur in associat ion w it h t he primary ant iphospholipid ant ibody syndrome.
Chorea w it h dement ia may occur f rom paraneoplast ic st riat al encephalit is[294]
and paraneoplast ic chorea may be associat ed w it h CRMP-5 neuronal ant ibody
and lung carcinoma[301] . Chorea may also be seen in variant Creut zf eldt -Jakob
disease (vCJD). A physiologic f orm of chorea is present in some inf ant s. Chorea
may occur in children as a sequelae of cardiac surgery (“postpump chorea”),
especially associat ed w it h prolonged t ime on t he pump, deep hypot hermia, or
circulat ory arrest [224] , and choreoat het osis and orof acial dyskinesia, hypot onia,
and pseudobulbar palsy (CHAP syndrome). CHAP syndrome may occur af t er
surgery f or congenit al heart disease[123] . A st eroid-responsive chorea has been
described af t er heart t ransplant [38] . Chorea may also be seen in pregnancy
(chorea gravi darum), and w it h t he administ rat ion of oral cont racept ives[214] ,
congophilic angiopat hy may cause chorea associat ed w it h progressive
dement ia[ 32] . Chorea is t he commonest movement disorder f ollow ing a st roke
and appears in older pat ient s[5] . Af t er a st roke, involunt ary movement s t end t o
persist despit e t he f unct ional recovery of mot or def icit .
The pat hogenesis of choreif orm movement s is essent ially unknow n. The evidence
linking t hese abnormal movement s t o t he caudat e and put amen is by no means
convincing, because most associat ed disease processes (e. g. , Hunt ingt on's
disease) show diff use or mult iple lesions t hat aff ect ot her neural st ruct ures.
Dyst onia and choreoat het osis are rare associat ions of cervical cord lesions,
such as ependymoma, glioma, myxoma, demyelinat ion, t rauma, and cervical disc
prolapse[ 293] .
Unilat eral chorea (hemi chorea) is cust omarily seen w it h lesions of t he
cont ralat eral subt halamic nucleus of Luys or it s connect ions, alt hough it has also
been know n t o occur w it h lesions of t he t halamus or caudat e nucleus. The
choreic movement s may involve t he ent ire half of t he body or may spare t he
f ace. I t is of t en f ruit less and impract ical t o dist inguish hemichorea f rom
hemiballismus; in f act , t he t w o disorders probably represent opposit e ends of a
spect rum of hyperkinesias. Hemichorea may be seen w it h inf arct ion or
hemorrhage. I t may also occur as a complicat ion of t halamot omy or, rarely,
secondary t o moyamoya, t rauma, migraine, or neoplasm. Hemichorea on t he
right side has been described w it h a lef t put aminal cavernous angioma[92] .
An overview of t he numerous causes of chorea is out lined in Table 19-1.
TABLE 19-1 Causes of Chorea
Inherited disorders
Autosomal dominant
Huntington's disease-like 2
Spinocerebellar ataxias, including SCA 3,
Machado-Joseph disease, dentato-rubro-
pallidoluysian atrophy
Neuroferritinopathy
Benign hereditary chorea
Autosomal recessive
Aminoacidopathies
Basal ganglia calcification
Hallervorden-Spatz disease
(Pantothenate kinase–associated neurodegeneration)
Lesch-Nyhan syndrome
Lysosomal disorders
Neuroacanthocytosis
Porphyria
Tuberous sclerosis
Urea cycle disease
W ilson's disease
Others
Leigh's syndrome (subacute necrotizing
encephalomyelitis)
Mitochondrial disease
Familial dyskinesia and facial myokymia
Drug induced
Neuroleptics
Propofol
Anticonvulsants
Antiparkinsonian medications
Oral contraceptives
Amphetamines
Tricyclic antidepressants
Pemoline
Lithium
Digoxin
Toxic/metabolic
Alcohol
Anoxia
Carbon monoxide poisoning
Cocaine
Heavy metal poisoning
Hyperthyroidism
Hypoparathyroidism
Pregnancy
Hyper- or hyponatremia
Acquired hepatocerebral degeneration
Nutritional
Infection
Sydenham's chorea/PANDAS
HIV encephalitis
Tuberculous meningitis
Encephalitis lethargica
Prion disease: Creutzfeldt-Jakob disease, vCJD
Immunologic
Henoch-Schönlein purpura
Sarcoidosis
Multiple sclerosis
Behçet's disease
Vasculitis
Hashimoto's encephalopathy
Vascular
Infarction
Hemorrhage
Arteriovenous malformation
Polycythemia
Migraine
Congophilic angiopathy
Cerebral palsy
Tumors
Primary or secondary
Paraneoplastic
Others
Niemann-Pick disease (juvenile dystonic lipidosis)
Pelizaeus-Merzbacher disease
Sudanophilic leukodystrophy
Dopa-responsive dystonia (Segawa syndrome)
Trauma
Physiologic chorea of infancy
Senile chorea
Paroxysmal choreoathetosis
Fotopoulos syndrome
Postpump (cardiac bypass) chorea
CHAP syndrome (choreoathetosis and orofacial
dyskinesia, hypotonia, and pseudobulbar palsy)
Heart transplant
Psychogenic
Tardive Dyskinesia and Other Tardive Syndromes

Tardi ve dyski nesi a and ot her t ardive syndromes result f rom t reat ment w it h
neurolept ic drugs and ot her dopamine recept or blocking agent s, including drugs
used f or gast roint est inal problems (met oclopramide), depression (amoxapine,
perphenazine/ amit ript yline), and cough (promet hazine). O nset af t er exposure of
less t han 3 mont hs is possible but uncommon[73] . The abnormal involunt ary
movement s can appear w hen t he pat ient is t aking t he drug or af t er st opping t he
drug and may persist and can even remain permanent ly. Wit hdraw ing t he
off ending drug of t en exacerbat es t he severit y of t he movement s, w hereas
increasing t he dosage of t en ameliorat es t he movement s.
A variet y of movement abnormalit ies may occur as t ardive syndromes. The most
common tardi ve dyski nesi a pat t ern is repet it ive, almost rhyt hmical movement s
t hat can be labeled st ereot ypic and most of t en occurs in t he oral-lingual-buccal
area. These oral-buccal-lingual dyskinesias usually present as complex chew ing
movement s of t en associat ed w it h occasional popping out of t he t ongue and w it h
w rit hing movement s of t he t ongue at rest in t he mout h[148] . O t her part s of t he
body, such as t he hands, f eet , and t runk, may also develop rhyt hmical
movement s and t he abdominal and pelvic muscles may be aff ect ed, result ing in
t runcal or pelvic rocking or t hrust ing movement s. Respirat ory dyskinesias can
result in involunt ary chest and diaphragmat ic movement s[99] . Tardive dyskinesia
is of t en accompanied by a f eeling of unpleasant inner rest lessness (akathi si a)
t hat can be w hole body rest lessness or uncomf ort able sensat ions in a specif ic
part of t he body[36, 51] . The t hird most common movement pat t ern is tardi ve
dystoni a, w hich may be accompanied by t ardive akat hisia or t ardive dyskinesia
[ 49, 50, 163, 299] . Wit h t ardive dyst onia, t he abnormal movement s are more
sust ained and somet imes t orsional in nat ure. Facial dyst onia may occur in t he
f orm of blepharospasm or f acial grimacing, w hereas involvement of t he mandible
can result in t onic jaw deviat ion, jaw prot rusion, sust ained opening and closing of
t he jaw, or bruxism. Dyst onic post uring of t he neck is also common, part icularly
ret rocollis[ 159] . Tardive dyst onia can occur at all ages, w hereas classic t ardive
dyskinesia is more common in t he elderly. O t her abnormal movement s t hat may
occur less commonly as t ardive syndromes include myoclonus, t remor, oculogyric
crisis, and t ics.
Orofacial Dyskinesia
O rof aci al dyski nesi as[ 7] are abnormal involunt ary movement s of t he f acial
musculat ure, lips, and t ongue t hat may appear spont aneously, especially in
elderly edent ulous pat ient s, or in Hunt ingt on's disease, Sydenham's chorea, or
Wilson's disease. Their occurrence af t er prolonged neurolept ic t herapy (tardi ve
dyski nesi a)[ 148] f avors an et iology involving denervat ion supersensit ivit y of t he
st riat um. A unilat eral st riat onigral lesion may produce bilat eral orof acial-lingual
dyskinesia plus cont ralat eral hemidyst onia, suggest ing t hat t he basal ganglia of
one hemisphere may exert bilat eral orof acial-lingual mot or cont rol[147] . The
diff erent ial diagnosis of orof acial dyskinesia is out lined in Table 19-2.
Abdominal Dyskinesias
Abdomi nal dyski nesi as are cont inuous movement s of t he abdominal w all or
somet imes t he diaphragm[144, 175] . Their sinuous, rhyt hmic nat ure has led t o
t hem being called bel l y dancer's dyski nesi a. Abdominal dyskinesia may occur
af t er abdominal t rauma (e. g. , laparot omy) in some cases and may be associat ed
w it h abdominal myoclonus. These dyskinesias may also occur as a t ardive
syndrome.
Ballismus
Ballismus [165, 201, 303] is an involunt ary hyperkinesia of t en conf ined t o one
half of t he body (hemi bal l i smus), but it may involve a single ext remit y
(monobal l i smus) or, except ionally, bot h halves of t he body (parabal l i smus or
bi bal l i smus). Hemiballismus is charact erized by t he occurrence of sudden,
paroxysmal, large-amplit ude, f linging, t hrow ing movement s of t he arm and leg
cont ralat eral t o a lesion in or near t he subt halamic nucleus. These abnormal
movement s are of t en cont inuous during w akef ulness and cease w it h sleep.
Hemiballismus is of t en associat ed w it h decreased muscle t one in t he involved
ext remit ies.
Hemiballismus usually occurs w it h lesions t hat aff ect t he cont ralat eral
subt halamic nucleus of Luys[201] or disrupt t he aff erent or eff erent connect ions
of t his st ruct ure. Transient hemiballismus/ hemichorea has been described w it h an
ischemic lesion of t he ipsilat eral subt halamic nucleus[72] . Hemiballismus may
also result f rom lesions in t he caudat e, put amen, globus pallidus, precent ral
gyrus, or t halamic nuclei[180, 227] .
The simult aneous occurrence of hemiballismus w it h acut e ipsilat eral cent ral pain
has been described af t er ant erior pariet al art ery st roke[266] .
Hemiballismus/ hemichorea has been described in pat ient s w it h nonket ot ic
hyperglycemia w it h magnet ic resonance imaging (MRI ) st udies revealing high
signal int ensit y in t he cont ralat eral st riat um[187] . Hemiballismus is most
commonly caused by a discret e ischemic or hemorrhagic vascular lesion of t he
subt halamus[ 303] . I t is uncert ain w het her t he occluded vessels arise f rom t he
post erior t halamoperf orat ing, post erior communicat ing, or ant erior choroidal
art eries[ 107] . Hemiballismus has also been not ed w it h t umors, art eriovenous
malf ormat ions, encephalit is, abscess, syst emic lupus eryt hemat osus, acquired
immunodef iciency syndrome (AI DS), cyst icercosis, head t rauma, subdural
hemat oma, t uberculous meningit is, demyelinat ion, t uberous sclerosis,
Sydenham's chorea, nonket ot ic hyperglycemia, basal ganglia calcif icat ions,
mult iple syst ems at rophy (MSA), as a side eff ect of levodopa t herapy, oral
cont racept ives, or af t er surgery f or advanced Parkinson's disease (PD) [60, 90,
125, 227, 258, 303] . Bilat eral ballismus has been described af t er bilat eral basal
ganglia hemorrhagic inf arct s involving t he caudat e and put amen, w it h mult iple
sclerosis, w it h disseminat ed int ravascular cancer, w it h syst emic lupus
eryt hemat osus, af t er vent riculoperit oneal shunt ing, w it h nonket ot ot ic
hyperglycemia, w it h phenyt oin int oxicat ion, and w it h dopaminergic drug-induced
dyskinesia in PD[196, 248] .
TABLE 19-2 Differential Diagnosis of Orofacial

Dyskinesia
1. Chorea
1. Postencephalitic
2. Drug induced
1. Dopamine receptor blockers (classic tardive
dyskinesia)
2. Levodopa
3. Anticholinergic drugs
4. Phenytoin intoxication
5. Antihistamines
6. Tricyclic antidepressants
3. Huntington's disease
4. Hepatocerebral degeneration
5. Cerebellar infarction
6. Edentulous malocclusion
7. Idiopathic
2. Dystonia
1. Idiopathic cranial dystonia (Meige syndrome)
2. Symptomatic dystonias
1. Dopamine receptor antagonists (acute
dystonia, tardive dystonia)
2. Other secondary dystonias
3. Tics
4. Tremor
1. Parkinsonism tremor of jaw, tongue, and lips
2. Essential tremor of neck and jaw
3. Cerebellar tremor of neck and jaw
4. Idiopathic tremor of neck, jaw, tongue, or lips
5. Myoclonus
1. Facial myoclonus of central origin
2. Familial nocturnal facio-mandibular myoclonus
6. Others
1. Hemifacial spasm
2. Myokymia
3. Familial dyskinesia and facial myokymia
4. Facial nerve synkinesis
5. Bruxism
6. Epilepsia partialis continua
7. Oculomasticatory myorhythmia in W hipple's
disease
Adapted from Fahn S. The tardive dyskinesias. In:

Matthews W B, Glaser GH, eds. Recent advances in
clinical neurology, Vol 4. Edinburgh: Churchill
Livingstone, 1984:229–260.)
Akathisia
Akathi si a ref ers t o a f eeling of inner rest lessness t hat is of t en relieved by
movement [36, 51, 120] . The mot or act ivit y is, t heref ore, described by pat ient s
as a volunt ary eff ort t o relieve uncomf ort able sensat ions, alt hough in severe
cases t he need f or mot or act ivit y is beyond cont rol. Akat hit ic movement s are
t ypically complex and st ereot yped w it h movement s including “squirming” in a
chair, repet it ive shif t ing of w eight , crossing and uncrossing t he legs, inabilit y t o
remain seat ed, pacing,
rocking t he t runk, and even moaning, humming, or groaning. O t her movement

disorders associat ed w it h moaning sounds or humming include t ics,
oromandibular dyst onia, Hunt ingt on's disease, and parkinsonism[115, 229] . A
specif ic body part may be aff ect ed, w it h relief of t he perceived discomf ort
(burning or pain) at t ainable by movement . Common sit es f or t he discomf ort are
t he mout h and vagina[108] .
Akat hisia is most of t en due t o medicat ions, especially agent s t hat block
dopamine recept ors (e. g. , neurolept ics, ant iemet ics, t et rabenazine, reserpine). I t
can occur w it h init iat ion of drug t reat ment (acut e akat hisia), subsequent ly w it h
t he emergence of drug-induced parkinsonism, or af t er chronic t reat ment (t ardive
akat hisia), w it h t he lat t er usually made w orse by drug w it hdraw al. Akat hisia may
also be present in pat ient s w it h parkinsonism.
A dist inct clinical syndrome ref erred t o as hypotensi ve akathi si a has been
described in pat ient s w it h aut onomic f ailure w ho manif est habit ual, volunt ary,
t ransient ly suppressible, yet irresist ible leg movement s occurring only in t he
sit t ing posit ion[62] . Repet it ive leg crossing, muscle t ensing, f oot t w irling or
w iggling, or heel or t oe t apping w hile sit t ing may have compensat ed f or
ort host at ic hypot ension and raised syst olic and diast olic blood pressure.
Athetosis
Athetosi s is charact erized by slow, uncoordinat ed, t w ist ing, w rit hing, involunt ary
movement s of w ide amplit ude. These movement s predominant ly involve t he dist al
appendicular musculat ure, especially t he upper ext remit ies, alt hough f acial and
axial muscles may also be involved.
At het oid movement s may be unilat eral (hemi athetosi s) or bilat eral (doubl e
athetosi s) and may int erf ere considerably w it h act ivit ies of daily living. These
movement s are of t en associat ed w it h episodic muscular hypert onia aff ect ing t he
axial and appendicular muscles. The diff erent iat ion of at het osis f rom chorea and
dyst onia may at t imes be diff icult because it is not uncommon t o see a pat ient
w it h “mixed” dyskinesias (i. e. , choreoathetosi s).
At het osis is usually not ed w it h degenerat ive disorders (e. g. , Wilson's disease,
kernict erus, st at us marmorat us, perinat al anoxia) involving w idespread cerebral
st ruct ures, including t he globus pallidus, subt halamus, red nucleus, and midbrain
t egment um. A f ocal lesion (vascular or neoplasm) t hat damages t he st riat um but
spares t he mot or cort ex and it s eff erent s may rarely cause at het osis.
At het oid movement s must be diff erent iat ed f rom “pseudoat het oid” movement s,
w hich are not ed on at t empt s t o maint ain post ure (e. g. , ext ending t he arms) and
are due t o f ault y propriocept ion (as in lesions aff ect ing t he large peripheral
nerve f ibers, t he dorsal root ganglia, t he post erior columns and t heir
connect ions, or t he pariet al lobe)[ 280] .
Dystonia
Dystoni a is charact erized by slow, long-sust ained, cont ort ing, involunt ary
movement s and post ures involving proximal appendicular and axial muscles. The
dyst onic movement s are t ypically slow and “w rapping” (athetoti c dystoni a),
alt hough pat ient s may sporadically demonst rat e superimposed, rapid, involunt ary
jerks t ermed dystoni c spasms or myocl oni c dystoni a. The dyst onic post uring
result s in disabling and abnormal at t it udes (dystoni c postures) of t he aff ect ed
body part s (e. g. , t ort icollis, t ort ipelvis, lordot ic or scoliot ic post ures, inversion of
t he hands and f orearms, equinovarus def ormit y)[ 176] . Theref ore, t he
charact erist ic f eat ures of dyst onia include: (a) excessive co-cont ract ion of
ant agonist muscles during volunt ary movement , (b) overf low of cont ract ion t o
remot e muscles not normally employed in volunt ary movement , and (c)
spont aneous spasms of cocont ract ion[209] . Dyst onia can also be associat ed
w it h f ast , rhyt hmic, t remulous movement s (dystoni c tremor)[ 155] . Dyst onic
t remor of t he hand has been described af t er cont ralat eral ant erior t halamic
inf arct ion[ 63] . O cul ogyri c cri si s, t hought t o represent dyst onia of t he ocular
muscles, has been described w it h t he use of neurolept ics, neurolept ic malignant
syndrome, Wilson's disease, encephalit is let hargica, organophosphat e poisoning,
and w it h lesions of t he lent if orm nuclei. [ 160] .
Dyst onia may be general i zed and idiopat hic (dyst onia musculorum def ormans) or
sympt omat ic (drug-induced, Wilson's disease, Menkes disease, met achromat ic
leukodyst rophy, Lesch-Nyhan disease, homocyst inuria, hexosaminidase A and B
def iciencies, progressive supranuclear palsy (PSP), cort ical-basal ganglionic
degenerat ion (CBG D), GM1 and GM2 gangliosidosis), or it may be segmental ,
aff ect ing only one body part , and idiopat hic (spasmodic t ort icollis, w rit er's
cramp, musician's cramp or dyst onia, spasmodic dysphonia (SD),
blepharospasm, orof acial dyskinesia) or sympt omat ic (post hemiplegic dyst onia).
O ccasionally, dyst onia may be f ocal and t ask specif ic (i. e. , brought on only by
specif ic act ivit ies or occupat ions, such as w rit ing, t yping, playing golf , playing
t he piano, blow ing a horn[206] , et c. ), and associat ed w it h a t ask-specif ic
t remor[ 264] . O ne unusual f orm
of occupat ional-specif ic oromandibular hemidyst onia is “aucti oner's jaw”[ 276] .

Pat ient s w it h f ocal t ask-specif ic dyst onia demonst rat e cort ical sensory
represent at ion t hat is markedly abnormal and inappropriat ely act ivat e cort ical
regions (t ypically t he supplement ary mot or cort ex) t hat are not act ivat ed during
normal perf ormance of manual t asks. Acut e dyst onic camptocormi a (bending of
t he t runk) has been described w it h lent icular, most ly put aminal, vascular
lesions[ 241] .
Hemi dystoni a may f ollow lesions of t he cont ralat eral caudat e, lent if orm nucleus
(especially t he put amen), or t halamus, or a combinat ion of t hese st ruct ures [66,
114, 213, 235, 317] . I t may be due t o abnormal input f rom t he t halamus t o t he
premot or cort ex due t o lesions eit her of t he t halamus it self or of t he st riat um
project ing by w ay of t he globus pallidus t o t he t halamus[213] . The most common
et iologies of hemidyst onia include st roke, t rauma, and perinat al injury[66] . I n one
st udy, lesions associat ed w it h dyst onic spasms or myoclonic dyst onia t ended t o
be locat ed in t he st riat opallidal complex or t halamus cont ralat eral t o t he
dyst onia[ 189] . Lesions of t he st riat opallidal complex involved t he put amen
post erior t o t he ant erior commissure and ext ended variably int o t he dorsolat eral
caudat e nucleus, t he post erior limb of t he int ernal capsule, or t he lat eral
segment of t he globus pallidus. These lesions w ere cent ered in t he
“sensorimot or” part of t he st riat opallidal complex w it h a t rend t ow ard a
somat ot opical dist ribut ion. Lesions of t he t halamus w ere locat ed in t he vent ral
int ermediat e and vent ral caudal nuclei, w hereas t he vent ral oral ant erior and
post erior nuclei (w hich receive pallidal eff erent s) are largely spared[189] .
Paroxysmal hemidyst onia may occur w it h cont ralat eral midbrain lesions[278] .
Primary dyst onias may be of genet ic origin. Heredi tary chi l dhood-onset dystoni a
(i di opathi c torsi on dystoni a, DYT1) most commonly st art s bet w een age 6 and 12
years w it h dyst onia of t he f oot w hile w alking. The illness is slow ly progressive
and t he dyst onia becomes generalized. The disorder is usually aut osomal
dominant w it h reduced penet rance. The abnormal gene, locat ed on chromosome
9q, produces a prot ein called torsi n A w it h unknow n f unct ion[249] . O t her
aut osomal dominant dyst onias include DY T4, DY T6, DY T7, and DY T13[79] .
DO PA-responsi ve dystoni a (Segawa vari ant or heredi tary progressi ve dystoni a)
is an aut osomal dominant disorder linked t o chromosome 14q22. 1-q22. 2. This
disorder t ypically present s in childhood (age 5–6 years) w it h dyst onic
movement s and post ures t hat are remarkably responsive t o low doses of
levodopa[ 136, 277] . These children may also have f eat ures of parkinsonism,
low er ext remit y hyperref lexia, and bilat eral ext ensor plant ar responses of t en
misdiagnosed as “cerebral palsy. ” The dyst onic movement s and post ures may
show marked diurnal variat ions, being more pronounced in t he lat e af t ernoon,
evening, and night . The et iology f or t he disorder is most commonly a mut at ion in
t he G TP cyclohydrolase I gene, w hich leads t o a def iciency in t he product ion of
dopamine[ 143] . Since t he gene has been ident if ied, t he clinical spect rum of t he
disorder has been expanded t o include adult -onset parkinsonism, oromandibular
dyst onia, spont aneously remit t ing dyst onia, spast icit y w it h development al delay
mimicking cerebral palsy, and generalized hypot onia w it h proximal w eakness[79] .
DYT14 is a genet ic def ect t hat can also lead t o dopa-responsive dyst onia[130] .
Myocl oni c dystoni a (DY T11) is an aut osomal dominant syndrome w here
sympt oms include dyst onic myoclonus as w ell as more prolonged spasms[118] .
Tremor, similar t o essent ial t remor or act ion t remor, may also be present . There
is of t en a marked response t o et hanol. I n many f amilies, t he genet ic abnormalit y
has been ident if ied t o be in t he prot ein epsilon-sarcoglycan[ 18] . There is an X-
linked recessive dyst onia-parkinsonism called Lubag primarily f ound in t he
Philippine I slands[309] . Rapi d-onset dystoni a parki nsoni sm (DY T12) is a st riking
aut osomal dominant disorder charact erized by abrupt onset of dyst onia, usually
accompanied by signs of parkinsonism. The sudden onset of sympt oms over
hours t o a f ew w eeks, of t en associat ed w it h physical or emot ional st ress,
suggest s a t rigger init iat ing a nervous insult t hat result s in permanent neurologic
disabilit y[ 80] .
Focal dyst onias (e. g. , t ort icollis) are usually sporadic and occur in lat er lif e but
pat ient s may have more t han one f orm of dyst onia. There may w ell be a genet ic
basis f or f ocal dyst onias; f or example, one f amily w it h spasmodic t ort icollis
(DY T7) had a genet ic linkage t o chromosome 18p [190] . Secondary dyst onias
can be caused by a variet y of neurologic disorders including Parkinson's
disease, Wilson's disease, gangliosidoses, leukodyst rophies, Leigh's disease,
Hallervorden-Spat z disease, t he juvenile f orm of Hunt ingt on's disease,
cort icobasal ganglionic degenerat ion, and brain lesions aff ect ing t he put amen,
caudat e, and t halamus. Dyst onia can also be psychogenic[186] .
Schrag et al. described t he clinical f eat ures of 103 pat ient s present ing w it h
“f ixed dyst onia”[274] . Most pat ient s w ere f emale (84%) and had a young age of
onset (mean 29. 7 years). A peripheral injury preceded onset in 63% and spread
of dyst onia t o ot her body regions occurred
in 56%. Af t er an average f ollow up of 3. 3 years (overall disease durat ion 8. 6

years), part ial (19%) or complet e (8%) remission had occurred in a minorit y of
pat ient s. The f ixed post ures aff ect ed predominant ly t he limbs (90%), and rarely
t he neck/ shoulder region (6%) or jaw. The aut hors conclude t hat f ixed dyst onia
of t en occurs af t er a peripheral injury and t hat w het her t he disorder is primarily
neurologic or psychiat ric remains an open quest ion.
A classif icat ion of dyst onias is out lined in Table 19-3.
Torticollis
Torti col l i s ( i di opathi c cervi cal dystoni a, wryneck, nuchal dystoni a) [9, 40, 77,
152, 183, 200] is a hyperkinesia slight ly more f requent in w omen and
charact erized by t onic or clonic cont ract ion of t he neck musculat ure, especially
t he st ernocleidomast oid and t rapezius muscles. This t ype of cervical dyst onia
result s in a more or less st ereot yped f ixed or spasmodic deviat ion of t he head
int o an anomalous posit ion w it h t he chin t w ist ed t o one side or t he head
displaced backw ard (ret rocollis) or f orw ard (ant erocollis) in about a quart er of
t he pat ient s, lat erally (lat erocollis) in half of t hem, or, most of t en, in a
combinat ion of t hese abnormal post ures. By convent ion, spasmodic t ort icollis is
named by t he st ernocleidomast oid muscle t hat cont ract s. Spasmodic t ort icollis is
usually unilat eral, ceases during sleep, and increases w it h anxiet y and st ress.
O f t en, t he abnormal movement can be relieved by sensory t ricks, such as a light
t ouch on t he f ace (t he gest e ant agonist e). O t her eff ect ive maneuvers include
leaning against a high-backed chair, placing somet hing int o t he mout h, or pulling
t he hair[77] . Local pain is report ed by most pat ient s. About a t hird of t hem have
scoliosis or a secondary cervical radiculopat hy. I n addit ion t o cervical dyst onia,
approximat ely 10% t o 20% of t hese pat ient s have oral, mandibular, or hand-arm
dyst onia or blepharospasm[77, 152] . Tremor, part icularly involving t he head, is
present in approximat ely 60% of t he pat ient s[152] .
Tort icollis may be congenit al, t ardive, secondary t o acquired cervical spine
abnormalit ies (e. g. , cervical spondylosis, subluxat ion of t he cervical spine,
inf lammat ory disorders of t he cervical spine), or due t o upper spinal cord t umor
w it h syringomyelia[164] . Post t raumat ic cervical dyst onia may develop
immediat ely af t er relat ively mild t rauma t o t he neck[127] . Cervical dyst onia may
also rarely occur as a sign of a post erior f ossa t umor and ret rocollis has been
described w it h bilat eral put aminal hemorrhages[282] . Focal dyst onia may also
occur w it h lesions of t he lent icular and caudat e nuclei, especially inf arct s and
t umors [179] . Cervical dyst onia occurs, how ever, most of t en as an
ext rapyramidal disorder of unknow n et iology and pat hologic subst rat e
(spasmodi c torti col l i s or i di opathi c cervi cal dystoni a) and is t he most common
f orm of adult -onset f ocal dyst onia[77] .
Writer's Cramp, M usician's Dystonia, the Yips, and

Focal Lip Dystonia
Wri ter's cramp (graphospasm) [ 156, 158, 281] is a segment al dyst onia
charact erized by spasms, cramps, aches, and occasional t remors of t he hand
muscles induced by w rit ing. Examinat ion reveals no evidence of oromandibular,
axial, or appendicular dyst onia, blepharospasm, or t ort icollis. Musician's
dyst onia is a f ocal t ask-specif ic dyst onia induced only by playing cert ain musical
inst rument s[ 265, 275] . Focal hand dyst onia has been suggest ed t o be a
maladapt ive response of t he brain t o repet it ive perf ormance of st ereot yped and
at t ent ion-demanding hand movement s[265] . How ever, not all pat ient s w it h f ocal
hand dyst onia have a st rict hist ory of excessive hand use; f or example, pat ient s
w it h musician's dyst onia spend many hours per day w it h t heir at t ent ion f ocused
on inst rument al pract ice, w hereas many pat ient s w it h w rit er's cramp have a
hist ory of average hand use. Mirror dyst onia (dyst onia occurring in t he dominant
hand w hen w rit ing w it h t he ot her hand) w as not ed in 29 of 65 pat ient s w it h
w rit er's cramp in one st udy[156] . The et iology and pat hologic subst rat e are
unknow n. Some aut hors have suggest ed t hat t his dyst onia may be due t o an
abnormalit y of t he cont ralat eral primary and secondary supplement ary mot or
areas result ing in dysf unct ion in mot or programming[88] .
Up t o 30% of golf ers develop t he yi ps, an inabilit y t o complet e a golf st roke,
most of t en aff ect ing short put t s, w hich w orsens w it h anxiet y[2, 219] . Yips may
be organic (a t ask-specif ic dyst onia) or psychological (anxiet y or “choking”). The
f inding t hat yips-aff ect ed golf ers of t en have co-cont ract ion of w rist f lexors and
ext ensors suggest s t hat in many individuals t his disorder is a t ask-specif ic
dyst onia[ 2] .
Pat ient s have been described w ho present ed w it h t he acut e onset of a movement
disorder charact erized by a t onic, sust ained, lat eral and out w ard prot rusion of
one half of t he low er lip[168] . The movement disorder w as present at rest ,
w hereas in some pat ient s, it w as also present during speech. I n all cases, t he
abnormal lip post ure could be suppressed volunt arily and spont aneous
remissions w ere f requent . This may w ell represent a f ocal l i p dystoni a.
TABLE 19-3 Classification of Dystonias
1. Primary Dystonias
1. Sporadic—Usually adult-onset focal dystonia
(e.g., torticollis)
2. Genetic dystonias (Locus—Designation—Mode of
Inheritance)
1. DYT1/TOR1—Early onset primary torsion
dystonia, Oppenheim's dystonia—AD
2. DYT2—Autosomal recessive primary torsion
dystonia—AR
3. DYT3—X-linked dystonia parkinsonism, Lubag
—X-linked
4. DYT4—Non-DYT1 primary torsion dystonia,
predominant whispering dysphonia—AD
5. DYT5/GCH1—Dopa-responsive dystonia,
Segawa syndrome—AD
6. DYT5—Dopa-responsive dystonia—AR
7. DYT6—Adolescent onset primary torsion
dystonia of mixed type, German-Mennonite
origin—AD
8. DYT7—Adult-onset focal primary torsion
dystonia—AD
9. DYT8/PNKD—Paroxysmal dystonic
choreoathetosis/nonkinesigenic dyskinesia—
AD
10. DYT9/CSE—Paroxysmal choreoathetosis with
episodic ataxia and spasticity—AD
11. DYT10/PKD—Paroxysmal kinesigenic
dystonia/choreoathetosis
12. DYT11—Myoclonus dystonia—AD
13. DYT12—Rapid-onset dystonia-parkinsonism—
AD
14. DYT13—Early and late-onset focal or
segmental dystonia—AD
15. DYT14—Dopa-responsive dystonia—AD
16. DYT15—Myoclonus dystonia—AD
2. Heredodegenerative diseases (some overlap with
Genetic Dystonias)
1. X-linked dystonia
1. Lubag (X-linked dystonia-parkinsonism)
2. Autosomal dominant
1. Huntington's disease (especially childhood
form)
2. Spinocerebellar degenerations
3. Dentato-rubral-pallidoluysian atrophy
4. Hereditary spastic paraplegia with dystonia
5. Rapid-onset dystonia-parkinsonism
6. Neuroferritinopathy
3. Autosomal recessive
1. W ilson's disease
2. Ataxia telangiectasia
3. Neurodegeneration with brain iron
accumulation type 1
4. Hallervorden-Spatz disease (PANK 2-
associated neurodegeneration)
5. HARP syndrome (hypobetalipoproteinemia,
acanthocytosis, retinitis pigmentosa, and
pallidal degeneration)
3. Neurometabolic Disorders
1. Lipid disorders
1. Metachromatic leukodystrophy
2. Niemann-Pick type C
3. Hexosaminidase A and B deficiency
4. G M1 Gangliosidosis
5. G M2 Gangliosidosis
2. Amino acid disorders
1. Glutaric acidemia
2. Methylmalonic acidemia
3. Other enzyme deficiencies and metabolic
disorders
1. Neuroacanthocytosis
2. Rett syndrome
3. Lesch-Nyhan syndrome
4. Aceruloplasminemia
5. Tyrosine hydroxylase deficiency
6. Aromatic amino acid decarboxylase deficiency
4. Mitochondrial disease
1. Leigh's disease
4. Acquired processes
1. Infection
1. Viral encephalitis
2. Creutzfeldt-Jakob disease
3. Encephalitis lethargica
4. Reye's syndrome
5. Subacute sclerosing panencephalitis
6. Human immunodeficiency virus infection
2. Drugs and toxins
1. Levodopa and dopamine agonists
2. Anticonvulsants
3. Flecainide
4. Ergotamines
5. Carbon monoxide poisoning
6. Manganese toxicity
3. Endocrine
1. Hypoparathyroidism
4. Perinatal
1. Kernicterus
2. Athetoid cerebral palsy
3. Delayed-onset dystonia with cerebral palsy
5. Miscellaneous
1. Cerebral infarction or hemorrhage, including
posthemiplegic dystonia
2. Progressive supranuclear palsy
3. Cortical-basal ganglionic degeneration
4. Multiple sclerosis
5. Paraneoplastic brainstem encephalitis
6. Head trauma
7. Peripheral limb trauma
8. Post surgery (e.g., thalamotomy)
9. Electrical injury
6. Psychogenic dystonia
AD = autosomal dominant; AR = autosomal recessive.
Blepharospasm
Bl epharospasm is charact erized by int ermit t ent or sust ained spont aneous
f orcef ul eye closure t hat may render t he pat ient f unct ionally blind[55, 150] .
These movement s may occur in pat ient s w it h parkinsonism or t orsion dyst onia or
as a side eff ect of neurolept ic drugs. Blepharospasm has been described w it h
dorsomedial pont ine t egment al or upper brainst em lesions [10, 179] .
Blepharospasm is also seen w it h oromandibular dyst onia, as in Mei ge syndrome
(i di opathi c bl epharospasm-oromandi bul ar dystoni a) [15, 150, 208, 298] , a
condit ion probably relat ed t o dopaminergic predominance in t he st riat um.
Spasmodic Dysphonia
Spasmodi c dysphoni a (SD) [ 8, 106, 218, 253] or l aryngeal dystoni a is a
disorder of unknow n et iology charact erized by a t remulous, f orced voice w it h a
low t one and volume and of t en associat ed w it h f acial grimacing. Three subt ypes
of SD are described by percept ual and acoust ic vocal charact erist ics: adduct or,
abduct or, and mixed [11, 12, 13, 14, 53] . Adduct or SD is associat ed w it h
involunt ary hyperadduct ion of t he vocal f olds, result ing in a st rained or st rangled
voice qualit y. Abduct or SD is charact erized by involunt ary abduct ions of t he vocal
f olds, result ing in int ermit t ent burst s of breat hy phonat ion. Mixed SD is applied
t o pat ient s w ho exhibit a f ull range of t hese vocal charact erist ics. Pit ch breaks,
hoarseness, limit ed int ensit y range, and poor int ensit y cont rol are present in all
t hree t ypes[253] . I t has been proposed t hat SD is a cont inuum disorder in w hich
bot h t ypes of spasms occur w it h diff ering f requencies[53] .
Pat ient s w it h SD of t en have abnormal neurologic examinat ions, including
abnormal rapid alt ernat ing movement s and t remor, including voice t remor [12,
13, 14, 253] . Some aut hors view SD as an incomplet e expression of Meige
syndrome[ 150] , as an adult -onset f ocal dyst onia [202] , or as an abnormalit y of
t he mot or cont rol syst em t hat includes t he globus pallidus, put amen, t halamus,
and supplement ary mot or area [106, 188, 218, 253] .
Paroxysmal Dyskinesias
Paroxysmal dyski nesi as are a het erogeneous group of disorders t hat have in
common sudden abnormal involunt ary movement s out of a background of normal
mot or behavior. The abnormal movement s may be choreic, ballist ic, dyst onic, or
a combinat ion of t hese. They consist of episodic at t acks of involunt ary
movement s, may be classif ied according t o phenomenology, durat ion of at t acks,
and et iology [30, 46, 83, 101, 157, 184] , and include t he f ollow ing.
1. Paroxysmal kinesigenic dyskinesia (PKD) (paroxysmal kinesigenic

choreoat het osis). I n t hese pat ient s, at t acks of abnormal involunt ary
movement s (t ypically last ing seconds t o minut es) occur abrupt ly af t er a
sudden volunt ary movement or st art le. Hypervent ilat ion may also induce an
episode. Ballism, dyst onic post ures, chorea, at het osis, or any combinat ion of
t hese make up t he movement s, w hich are occasionally preceded by
parest hesias, t enseness, or craw ling sensat ions. The at t acks may cause
f alls and may aff ect speech. The abnormal movement s are easily habit uat ed
and t heref ore f ail t o recur if t he sudden movement is immediat ely repeat ed.
Alt hough t his abnormalit y is usually idiopat hic[46] , it may occur on a
heredit ary basis and has also been described
w it h mult iple sclerosis, head t rauma, PSP, put aminal/ t halamic inf arct ion,
hypoparat hyroidism w it h basal ganglia calcif icat ions, HI V inf ect ion, and
hyperglycemia w it h lent icular vascular malf ormat ion [37, 231, 262] . Families
w it h members t hat have PKD may have ot her members w it h inf ant ile
convulsions, suggest ing a shared PKD/ inf ant ile convulsions gene[292] .
Approximat ely 90% of pat ient s improve w it h medicat ions, especially
ant iconvulsant s.
Bruno et al. review ed t he clinical f eat ures of 121 aff ect ed individuals w it h a
presumpt ive diagnosis of idiopat hic PKD[46] . The majorit y (79%) of aff ect ed
subject s had a dist inct ive homogeneous phenot ype. The aut hors propose t he
f ollow ing diagnost ic crit eria f or idiopat hic PKD based on t his phenot ype:
ident if ied t rigger f or t he at t acks (sudden movement s), short durat ion of
at t acks (< 1 minut e), lack of loss of consciousness or pain during at t acks,
ant iepilept ic drug responsiveness, exclusion of ot her organic diseases, and
age at onset bet w een 1 and 20 years if t here is no f amily hist ory (age at
onset may be applied less st ringent ly in t hose w it h f amily hist ory). I n
comparing f amilial and sporadic cases, sporadic cases w ere more f requent ly
male, and inf ant ile convulsions w ere more common in t he f amilial kindreds.
Females had a higher remission rat e t han males. An inf ant ile-onset group
w it h a diff erent set of charact erist ics w as ident if ied. A clear kinesigenic
t rigger w as not elicit ed in all cases, ant iepilept ic response w as not universal,
and some inf ant s had at t acks w hile asleep.
2. Paroxysmal nonkinesigenic dyskinesia (paroxysmal dyst onic
choreoat het osis). Wit h t his ent it y, at t acks of involunt ary movement s (usually
last ing minut es t o hours) occur spont aneously and consist of combinat ions of
dyst onic post uring, chorea, at het osis, and ballism[154] . Speech is of t en
aff ect ed and at t acks may be preceded by parest hesias, st iff ness, or
craw ling sensat ions. These at t acks may occasionally be t riggered by st ress,
f at igue, excit ement , caff eine, or alcohol. Alt hough usually idiopat hic, t his
ent it y of t en occurs on a heredit ary basis and has also been described w it h
mult iple sclerosis, perinat al encephalopat hy, hypoparat hyroidism w it h basal
ganglia calcif icat ion, encephalit is, t hyrot oxicosis, st roke, inf ant ile hemiplegia,
head t rauma, hypoglycemia, AI DS, diabet es mellit us, anoxia, and brain
t umor[ 37, 231] . This abnormalit y may also occur on a f unct ional basis. Not
sensit ive t o ant iconvulsant s, only a t hird of t he pat ient s improve w it h
medicat ions.
3. Paroxysmal exert ion-induced dyskinesia. Wit h t his f orm, at t acks are
precipit at ed by prolonged physical exert ion. The abnormal movement s
especially aff ect t he legs.
All t hree t ypes may be f urt her subdivided int o short -last ing (5 minut es) and
long-last ing (> 5 minut es) at t acks.
4. Paroxysmal hypnogenic dyskinesia. I n t his f orm, episodes of involunt ary
movement s occur only during sleep.
5. I nf ant ile Convulsions and Choreoat het osis syndrome (I CCA syndrome).
Families w it h t his syndrome have members t hat suff er inf ant ile convulsions
and lat er develop episodes of paroxysmal choreoat het osis[30] . At t acks of
choreoat het osis resemble PKD in being very brief and f requent and induced
by sudden exert ion.
Many of t he heredit ary f orms of paroxysmal dyskinesia may be due t o

channelopat hies[ 30, 31] . O t her paroxysmal movement disorders t hat have been
described include benign paroxysmal dyst onia/ t ort icollis in inf ancy (Sandif er's
syndrome) and paroxysmal at axia and t remor. Sandi f er's syndrome is
charact erized by spasmodic post uring of t he head and neck as a result of
gast roesophageal ref lux[205] . Paroxysmal ataxi a and tremor may be associat ed
w it h persist ent limb myokymia or neuromyot onia, nyst agmus, or ocular mot ilit y
dysf unct ion.
Myoclonus
Myocl onus [ 3, 28, 56, 74, 153, 211, 246, 290] is a movement disorder
charact erized by unexpect ed, brief , brisk, shock-like, involunt ary, repet it ive,
synchronous or asynchronous cont ract ions of a muscle or group of axial or
appendicular muscles. These involunt ary movement s may be suff icient ly f orcef ul
t o displace t he aff ect ed part of t he ent ire body. Myoclonus may occur in
combinat ion w it h dyst onia (myocl oni c dystoni a)[ 245] .
Myoclonus may be f ocal, mult if ocal, or generalized. For example, diaphragmat ic
myoclonus (diaphragmat ic f lut t er) is a rare f ocal myoclonus causing repet it ive,
involunt ary cont ract ion of t he diaphragm and ot her inspirat ory muscles[61] .
Myoclonus may occur spont aneously or on at t empt ed movement (acti on
myocl onus)[ 185] and may be precipit at ed by cut aneous, audit ory, visual, or
muscular (e. g. , sudden muscle st ret ch) st imuli. Act ion or int ent ion myoclonus is
most of t en encount ered af t er cerebral hypoxia (Lance-Adams syndrome) and
w it h cert ain degenerat ive disorders, such as Ramsay Hunt syndrome. Myoclonus
is seen w it h st ruct ural or met abolic lesions of
t he spinal cord, brainst em, cerebellum, and cerebral cort ex or in normal

individuals (e. g. , “sleep st art s”). Rhyt hmic myoclonus is t ypically due t o
st ruct ural lesions of t he brainst em or spinal cord. Myoclonus has a relat ionship
t o seizures in t hat bot h appear t o be t he result of hyperexcit able neurons.
Marsden et al. [ 211] divide myoclonus int o f our major et iologies: (a) physiologic,
(b) essent ial, (c) epilept ic, and (d) sympt omat ic. Caviness classif ied myoclonus
as out lined in Table 19-4[ 56] .
Physi ol ogi c myocl onus occurs in neurologically normal individuals. Sleep is t he
most common circumst ance of physiologic myoclonus. The t w o physiologic f orms
of myoclonus during sleep or sleep t ransit ions include part ial myoclonic jerks
(“physiologic f ragment ary myoclonus”), consist ing of small, mult if ocal jerks
maximal in t he hands and f ace but present diff usely, and massive myoclonic jerks
(hypnic jerks). Part ial myoclonic jerks are usually mult if ocal and occur in dist al
limb muscles, w hereas hypnic jerks are generalized and aff ect t he t runk and
proximal limbs. Pathol ogi c t ypes of myoclonus t hat may occur during sleep
include isolat ed periodic movement s in sleep, rest less legs syndrome w it h
periodic movement s in sleep, and excessive f ragment ary myoclonus in non-rapid
eye movement (REM) sleep. Myoclonus w it h epilepsy, int ent ion myoclonus
associat ed w it h semi-volit ional movement s, and segment al myoclonus also occur
in sleep, but are not primarily noct urnal. Periodic movement s of sleep (PMS) or
periodic limb movement disorder (PLMD) occurs virt ually in all groups of pat ient s
ref erred t o a sleep disorder laborat ory and consist of repet it ive, st ereot yped
dorsif lexion of t he t oes and f oot , and, occasionally, f lexion of t he knee and hip.
Noct urnal myoclonus of t en occurs in associat ion w it h rest less legs syndrome.
PMS can be asympt omat ic f or t he pat ient , alt hough, as w it h all t ypes of
noct urnal myoclonus, t he disorder may cause dist ress t o t he pat ient 's spouse.
O n some occasions, how ever, PMS can induce sleep f ragment at ion and
excessive dayt ime sleepiness.
Essenti al myocl onus occurs w it hout any apparent et iology or associat ed gross
neurologic def icit and is charact erized by onset bef ore t he age of 20 years,
sporadic occurrence or dominant inherit ance w it h variable severit y, a benign
course compat ible w it h an act ive lif e and normal lif e span, absence of ot her
neurologic def icit s, and normal EEG [56] . Essent ial myoclonus is usually
dist ribut ed t hroughout t he upper body, is exacerbat ed by muscle act ivat ion, and
is of t en responsive t o small amount s of alcohol[181] . Some of t hese pat ient s
may exhibit element s of dyst onia. Mut at ions in t he gene encoding epsilon-
sarcoglycan may cause t he myoclonus-dyst onia syndrome[318] .
Epi l epti c myocl onus ref ers t o t he presence of myoclonus in pat ient s w it h
epilepsy. The myoclonus can occur as only one component of t he seizure, t he
only seizure manif est at ion, or one of mult iple seizure t ypes w it hin t he epilept ic
syndrome. The myoclonus is here presumed t o be of cort ical origin.
Acti on Myocl onus–Renal Fai l ure Syndrome (AMRF) is a dist inct ive f orm of
progressive myoclonus epilepsy associat ed w it h renal dysf unct ion[21] . The
syndrome w as not recognized bef ore t he advent of dialysis and renal
t ransplant at ion because of it s rapidly f at al course if renal f ailure is unt reat ed.
Badhw ar et al. described 15 individuals w it h AMRF f rom f ive count ries, including
a f ollow up of f our French–Canadian pat ient s[21] . Segregat ion analyses w ere
compat ible w it h aut osomal recessive inherit ance. AMRF can present w it h eit her
renal or neurologic f eat ures. Tremor (onset 17–26 years) and progressively
disabling act ion myoclonus (onset 14–29 years), w it h inf requent generalized
seizures (onset 20–28 years) and cerebellar f eat ures are charact erist ic.
Prot einuria, det ect ed bet w een ages 9 and 30 years in all cases, progressed t o
renal f ailure in 12 out of 15 pat ient s w it hin 0 t o 8 years af t er prot einuria
det ect ion. Brain aut opsy in t w o pat ient s revealed ext raneuronal pigment
accumulat ion. Renal biopsies show ed collapsing glomerulopat hy, a severe variant
of f ocal glomerulosclerosis. Dialysis and renal t ransplant at ion are eff ect ive f or
t he renal but not t he neurologic f eat ures, w hich cont inue t o progress even in t he
presence of normalized renal f unct ion; t he lat t er can be managed w it h
ant imyoclonic and ant iepilept ic drugs.
Symptomati c or secondary myocl onus occurs in t he set t ing of an ident if iable
underlying disease process as out lined in Table 19-4. Lesions responsible f or
f ocal or segment al causes of myoclonus may be localized t o t he cort ex,
t halamus, brainst em, or spinal cord. Familial noct urnal f acio-mandibular
myoclonus mimicking sleep bruxism may present w it h noct urnal t ongue bit ing and
bleeding[ 302] .
The opsocl onus-myocl onus syndrome may arise in a variet y of set t ings including
inf ect ions, t oxins, and a paraneoplast ic syndrome. I n t hese pat ient s myoclonus is
associat ed w it h conjugat e, involunt ary, large-amplit ude saccades in all direct ions
(saccadomani a). I n childhood, t he syndrome is of t en associat ed w it h
neuroblast oma.
TABLE 19-4 Classification of M yoclonus
Physiologic myoclonus (in healthy subjects)

Jerks during sleep (hypnic jerks)
Anxiety-induced myoclonus
Exercise-induced myoclonus
Hiccup (singultus)
Benign infantile myoclonus during feeding
Essential myoclonus
Hereditary (autosomal dominant)
Myoclonus-dystonia syndrome
Sporadic
Epileptic myoclonus (seizures dominate and no
encephalopathy, at least initially)
Fragments of epilepsy
Isolated epileptic myoclonic jerks
Epilepsia partialis continua
Idiopathic stimulus-sensitive myoclonus
Photosensitive myoclonus
Myoclonic absences in petit mal epilepsy
Childhood myoclonic epilepsies
Infantile spasms
Myoclonic astatic epilepsy (Lennox-Gastaut
syndrome)
Cryptogenic myoclonic epilepsy (Aicardi)
Awakening myoclonic epilepsy of Janz
Benign familial myoclonic epilepsy (Rabot)
Progressive myoclonic epilepsy—Baltic myoclonus
(Unverricht-Lundborg disease)
Symptomatic (secondary) myoclonus (progressive or
static encephalopathy dominates)
Storage diseases
Lafora body disease
Lipidoses—e.g., GM2 gangliosidosis, Tay-Sachs
disease, Krabbe's disease
Neuronal ceroid lipofuscinosis (Batten disease)
Sialidosis (“cherry-red spot” syndromes)
Non-infantile neuronopathic Gaucher disease
Action myoclonus-renal failure syndrome
Ataxic syndromes
Dyssynergia cerebellaris myoclonica (Ramsay Hunt
syndrome)
Friedreich's ataxia
Autosomal dominant cerebellar degenerations (e.g.,
SCA 2)
Other spinocerebellar degenerations
Basal ganglia degenerations
W ilson's disease
Torsion dystonia
Hallervorden-Spatz disease (pantothenate kinase–
associated neurodegeneration)
Progressive supranuclear palsy (Steele-Richardson-
Olszewski syndrome)
Parkinson's disease
Multisystem atrophy
Corticobasal degeneration
Dentatorubropallidoluysian atrophy
Dementia
Alzheimer's disease
Diffuse Lewy body disease
Viral encephalitis
Subacute sclerosing panencephalitis
Lethargic encephalitis
Arbovirus encephalitis
Herpes simplex encephalitis
HIV-related disease
Postinfectious encephalitis
Metabolic entities
Hepatic failure
Renal failure
Dialysis dysequilibrium syndrome
Hyponatremia
Hypoglycemia
Myoclonic encephalopathy of childhood
Nonketotic hyperglycemia
Multiple carboxylase deficiency
Biotin deficiency
Mitochondrial dysfunction (e.g., myoclonus epilepsy
and ragged red fiber syndrome [MERRF])
Toxic and drug-induced syndromes (e.g., bismuth,
heavy metals, methyl bromide, tricyclic
antidepressants, opioids, lithium, selective serotonin
reuptake inhibitors [SSRIs], dopaminergic agents)
Physical encephalopathies
Posthypoxic (Lance-Adams syndrome)
Posttraumatic
Heat stroke
Electric shock
Decompression injury
Serotonin syndrome
Focal nervous system damage
Poststroke
Post-thalamotomy
Tumor
Herpes zoster virus
Trauma
Olivodentate lesions (palatal myoclonus or palatal
tremor)
Peripheral nerve lesions
Malabsorption syndromes
Celiac disease
W hipple's disease
Paraneoplastic syndromes
Opsoclonus-myoclonus syndrome
Adapted from Caviness JN. Myoclonus. Mayo Clin Proc

1996;71:679–688.
Spi nal myocl onus involves repet it ive myoclonic jerking of an arm or leg, w it h
act ivit y in t he f lexors usually predominant , and may be due t o spinal cord
t rauma, t umor, or inf lammat ory lesions[111] . Spinal myoclonus may be of t w o
t ypes: simple segment al and propriospinal[45] . Simple spinal segment al
myoclonus consist s of f ocal, repet it ive, rhyt hmic jerks conf ined t o one or more
adjacent spinal segment s. Propriospinal myoclonus consist s of predominant ly
axial and of t en arrhyt hmic f lexor or ext ensor jerks involving many spinal
segment s linked by long propriospinal pat hw ays (nonrhyt hmic, repet it ive axial
myoclonic jerks causing symmet ric f lexion of t he neck, t runk, hips, and knees).
Propriospinal myoclonus may occur spont aneously and has also been described
w it h cervical hemangioblast oma, in t et raplegic pat ient s, w it h spinal cord
inf lammat ion, and w it h Lyme disease[45, 82] .
Pal atal myocl onus (pal atal tremor)[ 86, 215] is a rhyt hmic cont ract ion (60–
180/ minut e) aff ect ing t he palat al and pharyngeal st ruct ures of t en associat ed w it h
synchronous movement s of t he ocular muscles, diaphragm, head, and neck.
Palat al myoclonus (“palat al t remor” is a bet t er t erm) persist s in sleep and is
associat ed w it h lesions (usually vascular, t raumat ic, neoplast ic, or
demyelinat ing) t hat int errupt t he pat hw ay bet w een t he red nucleus, t he inf erior
olivary nucleus, and t he dent at e nucleus (G uillain-Mollaret t riangle). The inf erior
olivary nuclei, or a region of t he brainst em encompassing t he inf erior olivary
nuclei, are hypermet abolic in palat al myoclonus and may be t he generat or of t he
involunt ary movement s[94] . Palat al myoclonus may rarely be of cort ical origin
and secondary t o epilepsia part ialis cont inua (epilept ic palat al myoclonus)[ 296] .
Palat al myoclonus has been described in a pat ient w it h a lat eral t halamic
inf arct ion[ 57] . Psychogenic palat al t remor may also occur[314] .
Rhyt hmic palat al myoclonus (pal atal tremor) may be separat ed int o sympt omat ic
and essent ial t ypes [86, 87, 89] . Sympt omat ic rhyt hmic myoclonus is most of t en
due t o cerebrovascular and degenerat ive diseases, encephalit is, mult iple
sclerosis, and t rauma; is associat ed w it h ot her brainst em or cerebellar (or bot h)
sympt omat ology; begins generally in t he f ourt h t o sixt h decades; is more
common in males; has present ing complaint s usually not relat ed t o t he palat al
myoclonus; has f requent ext rapalat al involvement , rarely w it h ear-click; has a
more homogeneous f requency (107–164 cycles/ minut e) t han t he essent ial t ype
(26–420 cycles/ minut e); has a lif elong durat ion; and usually does not cease
during sleep. This t ype is t hought t o be secondary t o cerebellar or brainst em
disease w it h a hypert rophied inf erior olive believed t o represent t he generat ing
oscillat or. I n essent ial rhyt hmic palat al myoclonus, t here is no evidence of a
st ruct ural lesion; t he essent ial f orm may t heref ore be a f unct ional analog of t he
sympt omat ic f orm based on neurot ransmit t er changes only. Essent ial rhyt hmic
palat al myoclonus is not associat ed w it h ot her cerebellar or brainst em
sympt omat ology; has an age of onset about t w o decades earlier t han t he
sympt omat ic f orm; is equally common in males and f emales; present s usually
w it h ear click; is never associat ed w it h nyst agmus or ext remit y t remor; has a
mean f requency of 107 Hz; has a most ly persist ent durat ion, but remissions may
occur; and may or may not cease during sleep [86, 87, 89] . The ear-click in
palat al myoclonus may be due t o t he w alls of t he eust achian t ubes snapping
t oget her or, more likely, may occur during opening of t he w alls due t o t he sudden
breaking of t he surf ace t ension holding t he w alls of t he t ube t oget her[86] .
Sympt omat ic palat al t remor is likely due t o rhyt hmic cont ract ion of t he levat or
veli palat ini muscle,
and essent ial palat al t remor is likely due t o t ensor veli palat ini cont ract ion[87,
304] .
A subgroup of t he sympt omat ic f orm of palat al t remor has a syndrome of
progressi ve ataxi a and pal atal tremor ( PAPT)[ 270] . Sporadic PAPT is a subt ype
of sympt omat ic palat al t remor in w hich progressive cerebellar degenerat ion is
t he most sympt omat ic f eat ure. I nt ernuclear opht halmoplegia may be present . The
cause of sporadic PAPT remains uncert ain. I n some previous report s of sporadic
PAPT, t he combinat ion of brainst em or pont ine at rophy, parkinsonism, aut onomic
dysf unct ion, or cort icospinal t ract abnormalit ies suggest s a diagnosis of MSA,
alt hough pat hologic verif icat ion is lacking. Familial PAPT is associat ed w it h
marked brainst em and cervical cord at rophy w it h cort icospinal t ract f indings. Eye
movement abnormalit ies suggest a disorder of bot h t he cerebellum and t he
brainst em. Familial PAPT diff ers f rom sporadic PAPT in having marked at rophy of
cervical cord and brainst em w it h cort icospinal signs but w it hout hypert rophic
olivary appearance on MRI .
O cul opal atal myocl onus may be of t w o t ypes [234] :
1. Lat eral f orm, w hich is charact erized by jerky nyst agmoid eye movement s
w it h simult aneous oblique and rot at ory component s associat ed w it h
lat eralized palat al myoclonus.
2. Midline f orm, w hich is charact erized by vert ical t o-and-f ro pendular eye
movement s w it h symmet ric bilat eral palat al myoclonus.
Pat ient s w ho develop t he one-and-a-half syndrome (see Chapt er 8) f rom pont ine
lesions associat ed w it h f acial nerve paresis (“ei ght-and-a-hal f syndrome”) of t en
subsequent ly develop oculopalat al myoclonus mont hs t o years af t er onset of
ocular dysmot ilit y[315] .
Painful Legs and Moving Toes

Alt hough t here is no proof t hat t he syndromes discussed here or in t he next
sect ion are relat ed t o basal ganglia disorders, t hey are discussed in t his chapt er
t o f acilit at e comparison w it h ot her dyskinesias. The painf ul legs and moving t oes
syndrome is a disorder in w hich t he t oes of one f oot are in cont inual f lexion-
ext ension w it h some lat eral mot ion, associat ed w it h a deep pain in t he ipsilat eral
leg[ 93, 284] . The const ant movement has a sinusoidal qualit y and may even
occur during sleep[232] . The pain ranges in severit y f rom mild t o excruciat ing,
of t en has a deep, boring qualit y, and is not dist ribut ed in any specif ic
dermat omal, myot omal, or peripheral nerve dist ribut ion. The movement s give no
relief f rom t he pain and t he neurologic examinat ion is normal, except in cases
associat ed w it h peripheral neuropat hy including HI V-relat ed neuropat hy, or
radiculopat hy. Sleep pat t erns are alt ered, and pat ient s complain t hat t he pain
persist s during sleep. Alt hough usually “idiopat hic, ” in some pat ient s w it h t his
disorder t here is evidence of a lesion of t he spinal cord, lumbar root s, or in t he
peripheral nerves [93, 232, 238] . An analogous disorder aff ect s t he upper
ext remit ies (painf ul arms or hands and moving f ingers) inst ead of t he legs and
t oes [145, 289, 300] . A mot her and daught er have been described w ho bot h
present ed w it h involunt ary movement s of t he t oes similar t o t hose seen in painf ul
legs and moving t oes but w it hout any associat ed pain (“painless legs and moving
t oes”)[ 97] .
Restless Legs Syndrome and Periodic Limb Movements

of Sleep
Restl ess l egs syndrome (Ekbom's syndrome, also know n as “anxi etas ti bi arum”)
ref ers t o a condit ion in w hich t he pat ient not es unpleasant craw ling sensat ions of
t he legs, part icularly w hen sit t ing and relaxing in t he evening, w hich disappear on
w alking [58, 64, 98, 141, 247, 307] . Crit eria f or diagnosis include: (i) an int ense,
irresist ible urge t o move t he legs, usually associat ed w it h sensory complaint s,
including parest hesias and dysest hesias, (ii) mot or rest lessness, (iii) w orsening
of t he sympt oms w it h rest and relief w it h mot or act ivit y, and (iv) increased
severit y of sympt oms in t he evening or at night [64] . Arm rest lessness is report ed
by approximat ely half of t he pat ient s [228] and may be t he init ial sympt om[110] .
The neurologic examinat ion is normal in t hese pat ient s. The pain is usually
diff use, not limit ed t o a peripheral nerve or dermat omal dist ribut ion, and
described as a deep, aching, burning, t hrobbing, craw ling, crushing, t earing pain.
Myoclonic jerks or more sust ained dyst onic movement s may occur in t he lat e
evening. Most commonly in t he aged populat ion, t he disorder is of t en (at least
80% of pat ient s) associat ed w it h a hypnogenic dyskinesia know n as peri odi c l eg
movements of sl eep [ 64, 68, 139, 203] . These abnormal periodic movement s
appear as f lexor cont ract ions of one or bot h legs w it h dorsif lexion of t he f oot
and f lexion of t he knee and hip. They occur at int ervals of approximat ely every
20 seconds and usually occur in light st ages I or I I of non-REM sleep. Periodic
limb movement s of sleep have also been described w it h various disorders
involving t he spinal cord, including mult iple sclerosis, I saac's syndrome
(neuromyot onia), mot or neuron disease,
cervical spondylosis, spinal cord injuries, t umors, spinal anest hesia, and
syringomyelia[ 242] . Periodic limb movement during sleep may develop af t er
pont ine inf arct ion[161] . Periodic limb movement s of sleep seldom involve t he
upper limbs.
Most cases of rest less legs syndrome are idiopat hic and of t en pat ient s have a
f amily hist ory of t he disorder[247] . An associat ion has been not ed of rest less
legs syndrome w it h various medical condit ions, including diabet es mellit us,
vit amin def iciencies, iron def iciency anemia, pregnancy, uremia, malabsorpt ion,
carcinoma, amyloidosis, and chronic obst ruct ive pulmonary disease and t his
condit ion may, t heref ore, represent a f orm of sensory neuropat hy. Spinal cord
lesions (e. g. , mult iple sclerosis, at lant oaxial dislocat ion, cervical spondylosis)
may occasionally be associat ed w it h t his syndrome[135] .
Tics
Ti cs are sudden, rapid, usually st ereot yped, and predominant ly clonic
hyperkinesias. They may be w illf ully suppressed f or short periods of t ime and
disappear during sleep. Tics usually st art around t he eyes or mout h but may
spread t o t he neck or shoulders or become generalized. Tics may consist of
simple mot or movement s (e. g. , eye blinking, nose t w it ch, shoulder shrug, head
jerking), complex mot or movement s (e. g. , head shaking, skipping), simple phonic
sounds (e. g. , t hroat clearing, grunt ing, barking), or complex vocalizat ions (e. g. ,
coprolalia, hiccoughs, echolalia). Tics are common in childhood and most
commonly do not persist f or longer t han a year (transi ent ti c of chi l dhood). Tics
can persist int o adult lif e, alt hough t hey generally diminish in int ensit y and
f requency (chroni c motor ti c). Most pat ient s describe a “psychic t ension” t hat
builds up inside t hem t hat can be relieved by t he t ic movement . I n many pat ient s,
t ics are preceded by a sensory sympt om (“sensory ti cs”) t hat seems t o drive t he
mot or act , w hich is t ypically direct ed t o t he region of t he sensat ion. The mot or
act st ops t he sensory sympt om, w hich may t hen quickly recur. Some pat ient s
st at e t hat t heir abnormal movement s are ent irely “volunt ary” and direct ed t o deal
w it h t he sensory sympt oms.
Tics may occur secondary t o drugs (L-dopa, neurolept ics, met hylphenidat e,
carbamazepine, phenyt oin, phenobarbit al, lamot rigine[197] ), or st riat al disorders
(e. g. , neuroacant hocyt osis, encephalit is let hargica, post t raumat ic, post st roke,
af t er carbon monoxide poisoning), and may also occur in t he syndrome of G i l l es
de l a Tourette[ 47, 240] . This syndrome begins in childhood and is charact erized
by mult iple or single mot or t ics, of t en associat ed w it h vocalizat ion (grunt ing,
sniff ing, snort ing, barking, t hroat clearing, spit t ing, coughing) or occasionally
w it h more complicat ed mot or act ivit y, such as copropraxia (obscene gest uring),
echopraxia (imit at ions of act s), jumping, or kicking. Coprolalia (obscene
language), copropraxia (obscene gest uring), and echolalia (t endency t o repeat
w ords or sent ences recent ly spoken t o t he pat ient ) occur in less t han half of
aff ect ed individuals. The t ics of Touret t e's syndrome are of t en accompanied by
behavioral problems, such as obsessive-compulsive disorder, lack of impulse
cont rol, and at t ent ion def icit disorder. Coprolalia may also occur w it h Lesch-
Nyhan syndrome, post encephalit ic parkinsonism, choreoacant hocyt osis, and
ot her basal ganglia disorders. Adult -onset t ic disorders may be caused by
inf arct ion, t rauma, cocaine use, or neurolept ic exposure, or may be
idiopat hic[ 65] .
Recent ly, t here has been cont roversy concerning t he pot ent ial role of
ant ineuronal ant ibodies in Touret t e's syndrome. There appears t o be ant ibodies
in t he serum of pat ient s direct ed against t he st riat um[132] . Sw edo et al.
described a disorder called PANDAS ( Pedi atri c Autoi mmune Neuropsychi atri c
Di sorders Associ ated wi th Strep Inf ecti ons)[ 291] . There are f ive diagnost ic
crit eria: (a) presence of obsessive-compulsive disorder and/ or a t ic disorder, (b)
prepubert al sympt om onset , (c) episodic course of sympt om severit y, (d)
associat ion w it h st rept ococcal inf ect ions, and (e) associat ion w it h neurologic
abnormalit ies. I n some st udies, t here are increased ant ibodies in t he serum of
pat ient s w it h Touret t e's syndrome direct ed against st rept ococcal ant igens[67] .
Tremor
Tremor [ 23, 105, 131, 140, 149, 279, 316] , t he most common of t he dyskinesias,
is charact erized by involunt ary, rhyt hmic, oscillat ory movement s about a f ixed
point result ing f rom eit her alt ernat ing or synchronous cont ract ions of reciprocally
innervat ed ant agonist muscles. Tremor usually involves t he dist al ext remit ies
and, less of t en, t he head and neck.
Tremor is classif ied as physiologic (7–11 Hz) or pat hologic. Physiologic t remor is
of t en barely seen w it h t he unaided eye but may be enhanced (enhanced or
exaggerated physi ol ogi c tremor) by f at igue, anxiet y, w it hdraw al of opioids or
alcohol, t hyrot oxicosis, hypoglycemia, pheochromocyt oma, or medicat ions (e. g. ,
cat echolamines, st eroids, amphet amines, caff eine, or t heophylline) [279] .
Enhanced physiologic t remor is absent
at rest and present w it h maint ained post ure. Severe muscle f at igue may also
act ivat e physiologic t remor (“rock-cl i mbers tremor”). Pat hologic t remors are
classif ied as f ollow s:
1. Resti ng tremor (3. 5–7. 0 Hz) is seen in t he relaxed ext remit ies and
disappears or markedly at t enuat es w it h act ion. This t ype of t remor is usually
not ed w it h diseases aff ect ing t he basal ganglia and it s connect ions (e. g. ,
PD). I n PD, t ypical movement s include pronat ion–supinat ion of t he f orearm
and rhyt hmic movement s of t he t humb across t he f ingers (“pi l l rol l i ng”). The
t remor is of t en markedly asymmet ric or purely unilat eral at onset .
O ccasionally, t he t remor reappears w hen t he hands are held in an
out st ret ched post ure (i. e. , t here is a lat ency in t he onset of t he t remor vs. no
lat ency in t he onset of essent ial t remor w it h maint ained post ure). The t remor
occasionally also aff ect s t he chin, jaw, or t ongue.
2. Postural tremor (6–11 Hz) is most not iceable in ext remit ies t hat maint ain an
ant igravit y post ure (e. g. , benign essent ial t remor). There may also be
t it ubat ion of t he head, t remor of t he jaw, and t remulous speech.
3. Intenti on (ki neti c or acti on) tremor (3–7 Hz) is most prominent in goal-
direct ed movement (e. g. , f inger-t o-nose t est ing) and of t en increases in
amplit ude as t he t arget is reached. I nt ent ion t remor is usually associat ed
w it h lesions of t he cerebellar pat hw ays. Alt hough severe int ent ion t remor is
of t en called rubral tremor, t his implied clinicoanat omical correlat ion does not
exist because t he t remor may be seen w it h any cerebellar out f low lesion,
especially lesions of t he superior cerebellar peduncle (not t he red nucleus)
[ 279] . A kinet ic t remor may also occur as a variant of essent ial t remor[34] .
The most f requent t ype of abnormal post ural t remor is essenti al tremor[ 288] .
This disorder aff ect s men and w omen equally, but head t remor may be more
severe in w omen, w hereas post ural ext remit y t remor may be more severe in
men[ 288] . Age of onset of t he t remor has been report ed t o be bimodal, w it h
peaks in t he second and sixt h decades[198] , or unimodal, peaking in t he f if t h
decade[ 173] . The t remor of t en runs as an aut osomal dominant t rait in f amilies,
but no responsible gene abnormalit y has been ident if ied. Most f requent ly t he
t remor aff ect s t he hands, f ollow ed by t he head, voice, t ongue, legs, and t runk.
The t remor is charact erist ically absent at rest , present w it h maint ained post ure,
and most evident at t he end of a goal-direct ed movement . Essent ial t remor
rarely aff ect s t he jaw and t ongue (vs. Parkinson's t remor). An associat ed
dyst onia w as f ound f requent ly in some series[198] but not in ot hers[173] .
Likew ise, an increased incidence of PD in t his populat ion has been report ed by
some[ 173, 198] but not ot hers[23] . Some pat ient s have an int ent ional t remor
rat her t han a post ural t remor and in t hese pat ient s gait at axia may be present ,
suggest ing cerebellar involvement [287] . Rarely t he t remor persist s at rest .
Caut ion must be exercised w hen making a diagnosis of essent ial t remor in
pat ient s present ing w it h lat e-onset asymmet rical post ural t remor even if t here is
no rest t remor. Alcohol sensit ivit y of t remor, f amily hist ory of t remor, or
responsiveness t o bet a-blockers may not be helpf ul in diagnosing essent ial
t remor in t hese cases and some may develop PD in t he long t erm[59] . I n a st udy
of 13 pat ient s present ing w it h asymmet rical post ural t remor, t hought t o be
essent ial t remor by t remor charact erist ics, alcohol responsiveness, and f amily
hist ory, all pat ient s developed addit ional signs suggest ing PD on long-t erm
f ollow -up[ 59] .
Wi l son's di sease is an aut osomal recessive disease charact erized by liver
dysf unct ion, behavioral abnormalit ies, and abnormal movement s[221] . The gene
responsible lies on chromosome 13q14. 3 and encodes f or a copper-t ransport ing
P-t ype ATPase (ATP7B). The enzyme binds copper in it s large N-t erminal domain
and aids in t ransport across t he membrane. Mut at ions of t he gene lead t o f ailure
t o excret e copper in bile and cause syst emic copper poisoning. Pat ient s w it h
neurologic abnormalit ies usually present in t he second or t hird decade as an
akinet ic-rigid syndrome resembling parkinsonism; a generalized dyst onic
syndrome (pure chorea is uncommon); post ural and int ent ion t remor w it h at axia,
gait dist urbance, clumsiness, t it ubat ion, and dysart hria (“pseudosclerosis”); or a
psychiat ric illness. Neurologic involvement may include a charact erist ic large-
amplit ude “wi ng-beati ng” tremor demonst rat ed w it h t he shoulders abduct ed t o 90
degrees. Some pat ient s have aut onomic nervous syst em abnormalit ies[225] .
Psychiat ric manif est at ions include conduct disorders, cognit ive impairment ,
changes in personalit y or mood, dement ia, and, rarely, psychosis.
O pht halmologic abnormalit ies consist of Kayser-Fleischer rings (caused by
deposit ion of copper in Descemet 's membrane), “sunf low er” cat aract s, slow
saccadic eye movement s, and, rarely, opht halmoplegia.
Rapid, irregular, and asynchronous movement s of t he legs and t runk occurring
w hile st anding is called orthostati c tremor or “shaky l egs syndrome” [ 42, 138,
223, 297] . This t remor may be associat ed w it h loss of ext ensor t one in t he legs
(negat ive myoclonus). O rt host at ic t remor is a disorder of middle-aged or elderly
people and is charact erized by f eelings of unst eadiness in t he legs and a f ear of
f alling w hen st anding[223] . O t her associat ed sympt oms include diff icult y in
w rit ing w hen st anding, diff icult y in init iat ing w alking (part icularly af t er st anding
long enough t o induce t roublesome low er limb shaking), and discomf ort in t he
low er limbs w hen st anding[223] . Pat ient s st and on a w ide base but w alk
normally. The sympt oms are at t enuat ed by w alking, abolished immediat ely by
sit t ing, and are due t o high-f requency (13–18 Hz) burst f iring in w eight -bearing
muscles[ 223] . The t remor may also be evident in t he t runk and cranial
muscles[ 178] . I somet ric co-cont ract ion of t he arm and leg muscles also may
induce a 14 t o 18 Hz t remor in some pat ient s w hen t hey are supine or suspended
upright , suggest ing t hat muscle cont ract ion seems t o be t he crit ical f act or in
generat ing t he t remor rat her t han ort host asis per se[41] . Pat ient s w it h
ort host at ic t remor may have asymmet ric hypert rophy aff ect ing t he t high and calf
muscles[ 133] . Alt hough usually idiopat hic, ort host at ic t remor has been described
w it h pont ine lesions suggest ing t hat dysf unct ion of t he cerebellar connect ions or
relat ed pont ine st ruct ures may be involved in it s genesis[27] .
O rt host at ic t remor is an example of a task-speci f i c tremor. Anot her t ask-specif ic
t remor is primary w rit ing t remor, w hich aff ect s t he w rit ing act in isolat ion, w it h
lit t le or no associat ed post ural or kinet ic t remor int erf ering w it h ot her act s[22] .
Primary w rit ing t remor may be subclassif ied as being eit her a t ask-induced
t remor (t he t remor appears during w rit ing) or a posit ionally sensit ive t remor (t he
t remor appears w hile w rit ing or w hen adopt ing hand posit ion used in w rit ing)[ 22] .
Approximat ely, one-t hird of pat ient s w it h primary w rit ing t remor have a f amily
hist ory of t he disorder[22] . Vocal t remor of t en occurs in isolat ion or may be
associat ed w it h SD. Anot her t ype of rhyt hmic movement is t he painf ul “jumping”
of t he st ump af t er amput at ion[286] . I n t he rabbi t syndrome, t here is a rest ing
t remor (4–6 Hz) aff ect ing t he perioral (orbicularis oris) and perinasal muscles,
of t en associat ed w it h a popping-like sound caused as t he lips rapidly separat e.
This syndrome has been associat ed w it h t he administ rat ion of neurolept ics and
w it h PD[84] .
Tremor can occur as a psychogenic sympt om (psychogeni c tremor)[ 162] . Such
t remors can t ake many f orms but t he most common are act ion t remors w it h
alt ernat ing act ivit y in ant agonist muscles. Psychogenic t remors vary in amplit ude
more t han expect ed and may change f requency. Pat ient s can be assessed w hile
asking t hen t o t ap w it h one limb at specif ic f requencies[85] . Tremor amplit ude
may increase w it h w eight ing, somet hing t hat should not happen w it h organic
t remors[ 85] . Typically, psychogenic t remor is of sudden onset w it h involvement
of more t han one limb. The t remor is usually obvious in more t han one limb
posit ion and t here is a relat ive lack of progression.
Hypokinetic and Bradykinetic Disorders

Parkinsonism
Bradykinesia, rigidit y, rest ing t remor, f reezing, f lexed post ure (of t he neck,
t runk, and limbs), and disorders of post ural ref lexes are t he cardinal f eat ures of
parki nsoni sm[ 52, 119] .
Bradyki nesi a is t he most disabling manif est at ion of parkinsonism and is
charact erized by delay in t he init iat ion and execut ion of w illed movement s and a
general reduct ion of associat ed aut omat ic movement s. Bradykinesia explains (at
least part ially) t he f acial hypomimia, reduced blinking, impaired ocular
convergence, monot onous and low -volume speech (bradylalia, event ually leading
t o anart hria)[ 70] , drooling of saliva, micrographia, and slow shuff ling gait w it h
reduced associat ed movement s t hat occur in parkinsonism.
Ri gi di ty is charact erized by a plast ic resist ance t o passive movement s t hat
aff ect s bot h agonist and ant agonist muscles (e. g. , f lexors and ext ensors,
pronat ors, and supinat ors) t o a similar ext ent and t hat is const ant t hroughout t he
ent ire range of movement . Rigidit y aff ect s more axial and proximal limb muscles
and can be det ect ed early in t he disease process. The phenomenon of cogwheel
ri gi di ty is charact erized by periodic modif icat ions of muscle t one due t o t he
superimposed t remor t hat can be seen and f elt w hen passively moving t he
ext remit y. The akinet ic-rigid syndrome is charact erist ic of PD and due t o
abnormal dopaminergic input t o t he st riat um. An akinet ic-rigid syndrome may
also occur w it h ext ensive damage t o t he st riat um, as in t he West phal variant of
Hunt ingt on's disease, Wilson's disease, or st riat onigral degenerat ion (SND);
damage t o t he out put zone of t he basal ganglia (i. e. , t he medial globus pallidus
and t he subst ant ia nigra pars ret iculat a), as in PSP, t he progressive pallidal
degenerat ions, and Hallervorden-Spat z disease (pant ot henat e kinase–associat ed
neurodegenerat ion); and diff use cerebral condit ions, such as Pick's disease,
cort icobasal degenerat ion, hydrocephalus, and diff use cerebrovascular disease
(e. g. , mult iple
cerebral inf arct s or subcort ical vascular encephalopat hy). Theref ore, any
pat hologic change (or drug) t hat causes ext ensive bilat eral disrupt ion of t he
st riat opallidal complex or it s out put s can cause an akinet ic-rigid syndrome[209] .
Parkinsonian tremor is charact erist ically slow, of medium t o coarse amplit ude
(3. 5–7. 0 Hz); present at rest ; increased by emot ion, f at igue, st ress, and anxiet y;
absent in sleep; and decreased by volit ional act ivit y. I t t ypically aff ect s t he dist al
appendicular muscles, leading t o f lexion–ext ension movement s of t he
met acarpophalangeal and int erphalangeal joint s of t he f ingers and t humb,
adduct ion–abduct ion movement s of t he t humbs (“pill rolling”), and pronat ion–
supinat ion movement s of t he w rist s. I t of t en begins unilat erally in t he hand and
may be present init ially only in t he t humb or a single f inger. The t remor t hen
t ypically spreads t o t he ipsilat eral low er ext remit y (“hemiparkinsonism”) bef ore
involving t he opposit e half of t he body. I n addit ion t o rest ing t remor, an act ion
t remor (7–12 Hz) may be seen. Tremor of t he prot ruded t ongue is not
uncommon, w hereas t remors of t he head, lips, and jaw are less f requent .
Di sorders of postural f i xati on may aff ect t he head, t runk, limbs, or t he ent ire
body, result ing in f orw ard displacement of t he head, f orw ard or backw ard
inst abilit y of t he t runk, diff icult y in maint aining an erect post ure w hen being
slight ly pushed, and easy f alling.
Freezi ng phenomena are also common in PD and consist of t ransient periods,
usually last ing seconds, in w hich t he mot or act is halt ed, being st uck in
place[ 122] . I n f reezing, t he volunt ary mot or act being at t empt ed is halt ed
because agonist s and ant agonist muscles are spont aneously and isomet rically
cont ract ing. Freezing phenomena include st art -hesit at ion (f reezing w hen gait is
init iat ed), t urn-hesit at ion (f reezing w hen t urning), dest inat ion-hesit at ion (f reezing
w hen approaching a t arget ), f reezing w hen an “obst acle” is encount ered,
spont aneous sudden t ransient f reezing, palilalia or f reezing of speech (i. e. ,
repet it ion of t he f irst syllable of t he w ord t rying t o be verbally expressed),
apraxia of eye opening (levat or inhibit ion), and f reezing of limbs (e. g. , during
w rit ing or t eet h-brushing)[ 100] . Wit h st art -hesit at ion, t he f eet t ake short st icking,
shuff ling st eps bef ore t he pat ient can begin w alking; w it h progression t he f eet
become “glued t o ground. ” Freezing occurs in idiopat hic parkinsonism,
sympt omat ic parkinsonism, PSP, mult isyst ems at rophy, and may be idiopat hic
w it hout ot her f eat ures except loss of post ural ref lexes and mild bradykinesia [1,
19, 259] .
Pat ient s w it h parkinsonism may demonst rat e a “simian post ure” (f orw ard f lexion
of t he t runk, f lexion of t he elbow s, and part ial f lexion of t he knees), t he
“parkinsonian hand” (mild dorsif lexion of t he w rist , f lexion of t he
met acarpophalangeal joint s, ext ension and adduct ion of t he f ingers, and slight
ulnar deviat ion), and t he dyst onic f oot post ure[239] (ext ension of t he great t oe,
f lexion of t he t oes, arching of t he sole, and inversion of t he f oot ). O t her f eat ures
include sleep abnormalit ies, and pain, as w ell as a variet y of sensory complaint s,
const ipat ion, hesit ance and f requency of mict urit ion, seborrhea, hyperhidrosis,
exaggerat ed nasopalpebral ref lex (glabellar t ap or Myerson's sign),
blepharospasm, blepharoclonus, and oculogyric crisis. Abnormalit ies of speech
are common and include hypokinet ic dysart hria, hypophonia, bradyphrenia (slow
t o t hink or respond t o quest ions), t achyphemia (repet it ion of a w ord or phrase
w it h increasing rapidit y and decreasing volume), palilalia, inappropriat e silent
periods, and “t ip-of -t he-t ongue” phenomenon (a t ype of anomia in parkinsonism
t hat is a semant ic rat her t han a phonet ic ret rieval def icit )[ 216] . I n addit ion t o
mot or signs, pat ient s w it h PD may have behavioral signs and are of t en
dependent , f earf ul, indecisive, and passive. Depression occurs in 30% of
pat ient s, w hereas dement ia occurs in 40% and increases w it h age (below age
60, 8%; great er t han age 80, 69%)[ 217] .
Sudden onset of sl eep ( SO S), w it h no prior w arning sympt oms of drow siness,
can occur in people w it h PD[177] . The st rongest predict ors of SO S are
increasing age, male sex, longer disease durat ion, and t he presence of various
sleep dist urbances. Taking non-ergoline dopamine ant agonist s is more st rongly
associat ed w it h SO S in pat ient s below 70 years of age and in t hose w it h disease
durat ion less t han 7 years.
Camptocormi a (bent spi ne syndrome) is charact erized by an abnormal post ure
of t he t runk w it h marked f lexion of t he t horaco-lumbar spine, w hich increases
during w alking and abat es in t he recumbent posit ion[20] . O riginally t hought t o be
a psychogenic disorder, campt ocormia is recognized as a f eat ure of parkinsonian
and dyst onic disorders[20] . Et iologies include parkinsonism (idiopat hic PD, MSA,
aut osomal recessive juvenile parkinsonism, post encephalit ic parkinsonism),
dyst onia, spine def ormit ies, st roke, neuromuscular disease (amyot rophic lat eral
sclerosis, inclusion body myosit is, nemaline myopat hy), sodium valproat e use,
G raves' disease, paraneoplast ic, psychogenic, and idiopat hic[20] .
Parkinsonism is a clinical syndrome t hat can be classif ied as idiopat hic (e. g. ,
PD) or as secondary (e. g. , sympt omat ic parkinsonism). PD, t he most common
f orm of parkinsonism, is a chronic,
progressive disease of unknow n et iology, charact erized by a st riat al dopamine

def iciency as a result of loss of t he pigment ed neurons of t he subst ant ia nigra.
Know n causes of parkinsonism include drugs (e. g. , neurolept ics, reserpine,
t et rabenazine, lit hium, f luoxet ine, amiodarone, phenelzine, α -met hyl-para-
t yrosine, alpha-met hyldopa, meperidine, amphot ericin B, f lunarizine, cinnarizine,
dilt iazem, cyt osine arabinoside, et hanol, procaine), t oxins (e. g. , 1-met hyl-4-
phenyl-1, 2, 3, 6- t et rahydropyridine, manganese, carbon monoxide, carbon
disulf ide, cyanide, disulf iram, met hanol, t oluene, n-hexane, and ot her solvent s),
inf ect ions (e. g. , post encephalit ic, von Economo's disease, HI V, subacut e
sclerosing panencephalit is (SSPE), Mycopl asma pneumoni ae, Japanese B
encephalit is, West ern equine encephalit is, Coxsackie virus, neurosyphilis, et c. ),
vascular parkinsonism also know n as arteri oscl eroti c parki nsoni sm or l ower
body parki nsoni sm (e. g. , mult iple lacunar inf arct ion, cerebral amyloid
angiopat hy, Binsw anger's disease), met abolic processes (e. g. , Wilson's disease,
chronic hepat ocerebral degenerat ion, disorders of calcium met abolism w it h or
w it hout basal ganglia calcif icat ions, post hypoxic-ischemic injury), st ruct ural
processes (e. g. , t umors, art eriovenous malf ormat ions, t raumat ic encephalopat hy,
subdural hemat oma, hydrocephalus), or mult isyst em degenerat ive processes
(e. g. , Shy-Drager Syndrome [ SDS] , PSP, olivopont ocerebellar at rophy (O PCA),
SND, cort icobasal ganglionic degenerat ion, primary pallidal at rophy of Hunt , rigid
variant of Hunt ingt on's disease, Machado-Joseph disease, Hallervorden-Spat z
disease [ pan- t ot henat e kinase–associat ed neurodegenerat ion] ,
spinocerebellonigral degenerat ion, parkinsonism w it h depression and alveolar
hypovent ilat ion, idiopat hic dyst onia-parkinsonism, X-linked Lubag syndrome of
parkinsonism w it h dyst onia [ among Filipino men] , hemiparkinsonism-hemiat rophy,
Creut zf eldt -Jakob disease, G erst mann-St raüssler-Scheinker disease, Ret t 's
disorder, neuroacant hocyt osis, mit ochondrial disorders, Alzheimer's disease,
Pick's disease, parkinsonism-ALS-dement ia complex of t he West ern Pacif ic)
[ 172] . Welding-relat ed parkinsonism, clinically indist inguishable f rom idiopat hic
parkinsonism, has also been described[256] .
Stiff-Man (Stiff-Person) Syndrome

The sti f f -man (sti f f -person syndrome) is charact erized by progressive f luct uat ing
muscular rigidit y[44, 191] . This disorder is not t hought t o be a disorder of t he
basal ganglia but causes severe rigidit y. Typically, t he rigidit y aff ect s t he axial
muscles of t he back, abdomen, hips, and shoulders, causing excessive lordosis
w it h prominent cont ract ion of t he paraspinal muscles, a “board-like” abdomen,
and st iff ness of t he legs. Superimposed upon t his cont inuous st iff ness are
spasms provoked by excit ement , anxiet y, volunt ary movement , sudden noise, or
peripheral st imuli. These spasms are of t en int ensely painf ul and may be f orcef ul
enough t o f ract ure bones or dislocat e joint s. Somet imes volunt ary movement s
can provoke severe spasms causing t he pat ient t o f all “like a w ooden man. ” The
syndrome usually begins in t he f ourt h or f if t h decades and aff ect s men and
w omen equally. The onset of t he syndrome is usually gradual w it h increasing
painf ul t ight ness, st iff ness, and clumsiness of t he t runk and legs. O n examinat ion
t here is cont inuous muscular cont ract ion of t he paraspinal and abdominal
muscles w it h no ot her neurologic signs except brisk ref lexes. The illness is
slow ly progressive w it h st iff ness spreading f rom t he t runk t o t he hip and t hen t he
shoulder muscles, but t he f ace and dist al limbs are spared. Some pat ient s may
only have st iff ness of t he limbs called “sti f f l i mb syndrome”[ 25, 44] . O t her cases
may progress t o t he syndrome of progressive encephalomyelit is w it h
rigidit y[ 128] .
A cent ral, perhaps spinal cord origin f or t he spasms, rigidit y, and cont inuous
mot or act ivit y has been suggest ed, perhaps a def ect ive input of inhibit ory
pat hw ays ont o mot or neurons. St iff -person syndrome may be t riggered by West
Nile Fever[137] . The signif icance of t he associat ion of insulin-dependent
diabet es mellit us w it h st iff -person syndrome has been emphasized by t he
discovery of ant ibodies direct ed against glut amic acid decarboxylase (G AD), t he
enzyme responsible f or t he synt hesis of G ABA, in bot h blood and cerebrospinal
f luid in 60% or more of pat ient s [305] . Most of t hese pat ient s also have
ant ibodies direct ed against pancreat ic islet cells as w ell as gast ric pariet al cells
and t he t hyroid. Ant i-G AD ant ibodies may damage G ABAergic inhibit ory
mechanisms in t he spinal cord.
St iff -person syndrome has been associat ed w it h ant iamphiphysin I ant ibodies in
pat ient s w it h breast cancer[268] and may occur w it h ot her paraneoplast ic
neurologic disorders, including sensory neuropat hy, cerebellar at axia, and
opsoclonus.
Cortical-Basal Ganglionic (Corticobasal) Degeneration

Corti cal -basal gangl i oni c degenerati on (CBG D) or corti co-dentato-ni gral
degenerati on w it h neuronal achromasia is a dist inct disease w it h clinical
f eat ures ref erable t o bot h cort ical and basal ganglionic dysf unct ion [26, 121,
174, 194, 260, 261, 312] . The illness begins in t he sixt h or sevent h decade w it h
f ocal dyst onia and myoclonus of an arm, t he alien hand sign (see Chapt er 20), or
an akinet ic-rigid syndrome. The most common init ial complaint is unilat eral
clumsiness, st iff ness, or jerking of t he arm[261, 312] . The clinical hallmark of
CBG D is a unilat eral parkinsonism unresponsive t o levodopa t herapy associat ed
w it h limb ideomot or apraxia[312] . Pat ient s develop a supranuclear gaze palsy in
bot h vert ical and horizont al direct ions, parkinsonian f eat ures, and cerebellar
signs. O t her f indings include const ruct ional dyspraxia w hen using t he arms,
cort ical sensory loss, apraxia, post ural-act ion t remor, act ion-induced or
st imulus-sensit ive myoclonus, hyperref lexia, gait disorders, post ural inst abilit y,
mild dysart hria, and dement ia[250] . Aphasia may be signif icant [109] and t he
disorder may even present as a primary progressive aphasic syndrome [29,
269] . Language dysf unct ion is common, even in pat ient s w it hout aphasia, w it h
prevalent phonologic and spelling impairment s[129] . O t her at ypical present at ions
include memory loss, dement ia, behavioral changes, and diff icult ies w it h speech
and gait [29, 273, 312] . O t her ocular mot or f indings include saccadic pursuit ,
hypokinet ic vert ical saccades, diff icult y init iat ing volunt ary saccades and pursuit ,
and oculogyric crisis[267] . The sympt oms and signs are of t en st rikingly
asymmet ric, and t he durat ion of t he disease is usually 4 t o 6 years [121, 260,
261] .
I t should be not ed t hat t here is pat hologic het erogeneit y of t he clinical diagnosis
of CBG D. I n a pat hologic st udy of 13 cases w it h t his clinical diagnosis, 7
pat ient s had CBG D, 2 had Alzheimer's disease, 1 had PSP, 1 had Pick's disease,
1 had Creut zf eldt -Jakob disease, and 1 pat ient had nonspecif ic f indings[39] .
There are of t en blurred clinical boundaries bet w een CBG D and PSP. Limb
dyst onia and apraxia may occur in pat ient s w it h ot herw ise classic supranuclear
vert ical gaze def icit and post ural impairment of PSP. Pat ient s w it h CBG D may
have a supranuclear vert ical gaze def ect lat e in t he course of t heir illness and
somet imes t he charact erist ic asymmet ric dyst onic limb is absent . Cases of
CBG D have also been report ed w here t he clinical prof ile f it s a pat t ern of f ront al
dement ia similar t o t hat seen w it h t he pat hologic ent it y f ront ot emporal dement ia
(FTD). I n f act , CBG D shares a common genet ic basis w it h PSP and FTD[91] .
These t hree condit ions are t heref ore best view ed as part of a spect rum of
disorders of t he t au gene (tauopathi es), w it h clinical sympt oms ref lect ing t he
cort ical or subcort ical locat ion of pat hology [91, 142] .
Progressive Supranuclear Palsy (Steele-Richardson-

Olszewski Syndrome)
PSP is a dist inct clinicopat hologic ent it y, t he hallmark of w hich is supranuclear
opht halmoplegia involving vert ical gaze [69, 112, 146, 193, 194, 195, 236, 285] ,
w hich may be overcome by t he oculocephalic maneuver. O t her clinical f eat ures
include pseudo-bulbar palsy (dysphagia and speech diff icult y), axial dyst onia in
ext ension (ret rocollis), rigidit y aff ect ing t he neck more t han t he limbs,
bradykinesia, post ural inst abilit y w it h backw ard f alls, a w ide-based shuff ling
gait , personalit y changes, a st aring unblinking f acies, sit t ing “en bloc, ” mild
dement ia, and cerebellar and cort icospinal t ract signs [69, 112, 170] . Mild
changes in t runcal muscle t one w it h prominent neck dyst onia and rigidit y are
charact erist ic[ 295] . Tremor is usually absent . I n cont rast t o t he short and
shuff ling st eps, st ooped post ure, narrow base, and f lexed knees t ypically seen in
PD, pat ient s w it h PSP have a st iff and broad-based gait , w it h a t endency t o have
t heir knees (and t runk) ext ended and t heir arms slight ly adduct ed. I nst ead of
t urning “en bloc, ” t hey t end t o pivot , w hich f urt her compromises balance.
Pat ient s may present w it h “pure akinesia, ” also ref erred t o as motor bl ocks or
gai t i gni ti on f ai l ure, and f reezing may be an early sign of impending PSP[259] .
O f t en pat ient s w it h PSP have deep f acial f olds and a t ypical “w orried” or
“ast onished” f acial expression. This f acial expression is charact erist ic of PSP
and diff ers f rom t he lack of f acial expression (hypomimia) seen w it h PD. The
f acial expression may be due t o a f ocal dyst onia of t he procerus muscle as w ell
as t o a combinat ion of reduced blinking, lid ret ract ion, and gaze palsy. Procerus
is a f acial muscle t hat originat es in t he nasal bone and insert s in t he skin in t he
cent er of t he f orehead bet w een t he eyebrow s; it act s f orming vert ical w rinkles in
t he glabella region and bridge of t he nose. The w rinkling of t his region is present
w it h open or closed eyes and is called t he procerus si gn[ 263] .
The dysart hria w it h PSP usually has a combinat ion of spast ic, hypernasal,
hypokinet ic, and at axic component s, but one of t hese element s may
predominat e; st ut t ering, dysphasia, apraxia of phonat ion, and palilalia may also
occur [151, 169, 194] . While most pat ient s demonst rat e a low -pit ched,
monot onous dysart hria, some pat ient s have almost cont inuous involunt ary
vocalizat ions
including loud groaning, moaning, humming, and grunt ing sounds. As a result of
chew ing diff icult ies, inabilit y t o look dow n, and poor hand coordinat ion, pat ient s
w it h PSP are of t en described as “sloppy eat ers”[195] . Less common f indings
t hat do not exclude t he diagnosis include limb rigidit y great er t han axial rigidit y,
a narrow -based gait , mild rest t remor, upper limb apraxia, upper limb at axia,
myoclonus, chorea, and respirat ory dist urbances[69] . Spont aneous arm
levit at ion, alt hough usually charact erist ic of CBG D, may somet imes occur[24] .
The init ial ocular mot or def icit consist s of impairment of vert ical saccades, w it h
dow nw ard saccades usually aff ect ed f irst . O t her ocular abnormalit ies include a
disproport ionat e hypomet ria of vert ical compared t o horizont al saccades
producing a curved course of oblique saccades, abnormal smoot h pursuit ,
blepharospasm, apraxia of eyelid opening and closure, pt osis, bilat eral lid
ret ract ion, decreased blinking, loss of Bell's phenomenon, int ernuclear
opht halmoplegia (t he adduct ion limit at ion may, how ever, at t imes be overcome by
vest ibular st imulat ion), nyst agmus, square-w ave jerks, ocular f lut t er, impaired
convergence, lat eral gaze palsies, and impaired perf ormance of ant isaccade
t asks (see Chapt er 8) [81, 112, 113, 126, 146, 204, 267] . All pat ient s w it h PSP
show ed slow volunt ary vert ical saccades and nyst agmus quick phases compared
w it h PD or cont rols[117] . Small, paired, horizont al saccadic int rusions (square
w ave jerks) are more f requent and larger in PSP during f ixat ion. Pat ient s of t en
lose t he abilit y t o read and make eye cont act and of t en complain of diplopia and
phot ophobia[ 236] . At a st age w hen f ull vert ical excursions are st ill present , some
pat ient s display an inabilit y t o produce pure vert ical saccades along a st raight
line in t he midline. I nst ead, t hey can only accomplish vert ical saccades by
moving t heir eyes in a lat eral arc (t he “round the houses” si gn)[ 255] . Lat e in t he
development of t he disease, t he ocular mot or def icit may progress t o a complet e
opht halmoplegia. The age of onset of t his disease process is usually in t he sixt h
and sevent h decade (average age 63 years), w it h deat h occurring in 2 t o 12
years[ 285] . Early onset , t he presence of f alls, slow ness, and inabilit y t o move
t he eyes dow nw ard early in t he development of t he disease predict poor survival
t ime[ 271] . Rarely, t he disease may occur w it hout t he classic supranuclear gaze
palsy [69, 75, 78, 167] . O t her disorders t hat present w it h supranuclear
opht halmoplegia and mot or f indings similar t o PSP, t hereby mimicking t his
disease, include cort ical (diff use) Lew y body disease[102] and idiopat hic
st riopallidodent at e calcif icat ions[272] . As not ed in t he preceding t ext , PSP
shares a common genet ic basis w it h CBG D and FTD (t auopat hies)[ 91] .
I n a st udy of t he clinical f eat ures of pat ient s w it h pat hologically proven PSP,
CBG D, PD, diff use Lew y body disease, Pick's disease, and MSA, t he f ollow ing
w ere not ed[194] :
1. Supranuclear vert ical gaze palsy, moderat e or severe post ural inst abilit y, and
f alls during t he f irst year af t er onset of sympt oms w ere most consist ent w it h
PSP.
2. Unst able gait , absence of t remor-dominant disease and absence of response
t o levodopa diff erent iat ed PSP f rom PD.
3. Supranuclear vert ical gaze palsy, gait inst abilit y, and t he absence of
delusions dist inguished PSP f rom diff use Lew y body disease.
4. Supranuclear vert ical gaze palsy and increased age at sympt om onset
dist inguished PSP f rom MSA.
5. G ait abnormalit y, severe upw ard gaze palsy, bilat eral bradykinesia, and
absence of alien limb syndrome separat ed PSP f orm CBG D.
6. Post ural inst abilit y classif ied PSP f rom Pick's disease.
The “appl ause si gn” (a t endency t o init iat e an aut omat ic program of applause
w hen one is asked t o init iat e a volunt ary program of t hree claps) is a simple t est
of mot or cont rol t hat helps t o diff erent iat e PSP f rom f ront al or st riat of ront al
degenerat ive diseases. I t w as f ound in 0/ 39 cont rols, 0 of 24 pat ient s w it h FTD,
0 of 17 pat ient s w it h PD, and 30 of 42 pat ient s w it h PSP[95] .
The area of t he midbrain on mid-sagit t al MRI can diff erent iat e PSP f rom PD,
mult iple syst em at rophy w it h parkinsonism (MSA-P), and normal aging[244] . The
average midbrain area of t he pat ient s w it h PSP w as signif icant ly smaller t han
t hat of t he pat ient s w it h PD and MSA-P and t hat of t he age-mat ched cont rol
group. The values of t he area of t he midbrain show ed no overlap bet w een
pat ient s w it h PSP and pat ient s w it h PD or normal cont rol subject s.
Lewy Body Dementia

Lewy body dementi a ( dementi a wi th Lewy bodi es), a common cause of
dement ia, is a pat hologically def ined disease process w it h t he f ollow ing
charact erist ic clinical f eat ures [4, 199, 222] :
1. Progressive disabling ment al impairment , at t ent ional impairment s, and

disproport ionat e problem solving and visuospat ial diff icult ies are of t en early
and prominent .
2. Fluct uat ions in cognit ive impairment w it h pronounced variat ion in at t ent ion
and alert ness, persist ent w ell-f ormed and det ailed visual hallucinat ions (e. g. ,
colorf ul images of animals or people), and spont aneous mot or f eat ures of
parkinsonism are core f eat ures.
3. Feat ures t hat support t he diagnosis include repeat ed f alls, syncope,
t ransient loss of consciousness, neurolept ic sensit ivit y, syst emized
delusions, and hallucinat ions of ot her modalit ies.
The average age of onset of t his disorder is 68 years. Parkinsonian f eat ures are
bilat eral and symmet ric. Pat ient s may have rest t remor, bradykinesia, and
rigidit y similar t o PD, but t he occurrence of myoclonus, absence of rest t remor,
no response t o levodopa, or no perceived need t o t reat w it h levodopa are much
more likely in Lew y body disease t han PD[199] . REM-sleep behavior disorder
has been associat ed w it h Lew y body dement ia.
Multiple Systems Atrophy

MSA encompasses a group of sporadic progressive adult -onset disorders
charact erized clinically by aut onomic dysf unct ion, parkinsonism, and at axia in
any combinat ion [254, 310, 311, 313] . The t hree major cat egories of MSA
include t he SDS, SND, and sporadic O PCA. Feat ures include t he f ollow ing:
1. Parkinsonism, usually w it h a poor or unsust ained response t o chronic

levodopa t herapy
2. Cerebellar or cort icospinal t ract signs
3. O rt host at ic hypot ension, impot ence, urinary ret ent ion or incont inence, usually
preceding or w it hin 2 years af t er onset of t he mot or syst em
Parkinsonism and upper mot or neuron signs are t he predominant mot or disorders
in SND, w hereas gait at axia, dysart hria, and dist urbances in execut ive cognit ion
are t he usual present at ion of t he O PCA t ype of MSA. SND is also associat ed
w it h laryngeal st ridor and sleep apnea. SDS is dominat ed by aut onomic
dysf unct ion. O nset of t he disorder is bet w een 40 and 69 years of age[310] . I n a
review of 188 pat hologically proved cases of MSA, 28% had all f our syst ems
involved; 18% had a combinat ion of parkinsonism, pyramidal, and aut onomic;
11% had parkinsonism, cerebellar, and aut onomic; 11% had parkinsonism and
aut onomic f indings; 10% had only parkinsonism; and parkinsonism w as absent in
11% of cases[254] . I n anot her series, aut onomic sympt oms w ere present at
onset in 41% of pat ient s and 97% developed aut onomic sympt oms during t he
course of t he disease[310] . I mpot ence is t he most f requent aut onomic sympt om
in males, w hereas urinary incont inence predominat ed in w omen. O rt host at ic
hypot ension is of t en t he most disabling aut onomic manif est at ion. O t her
aut onomic manif est at ions in SDS include anhidrosis, decreased t earing, and iris
at rophy. Nearly half of all pat ient s are markedly disabled or w heelchair bound
w it hin 4 years of t he onset and t he median survival is 9. 5 years. Parkinsonism
associat ed w it h neck ext ensor myopat hy (head drop) may occur w it h MSA[16] .
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> Table of C ontents > C hapter 20 - The Loc aliz ation of Les ions Affec ting the C er ebr al Hem is pher es
Chapter 20
The Localization of Lesions Affecting the
Cerebral Hemispheres
Localizat ion of lesions in t he cerebral hemispheres relies on t he underst anding of

t he f unct ion of diff erent port ions of t he cerebral cort ex. I nit ially, hemispheric
localizat ion w as learned f rom t he clinical eff ect s of vascular or ot her lesions,
t rue “experiment s of nat ure. ” Limit ed cort ical act ivat ion procedures w ere
perf ormed int raoperat ively since t he 1920s, but in t he last f ew years, cort ical
mapping has expanded prodigiously w it h t he advent of f unct ional neuroimaging.
The t w o t echniques most ext ensively used are posit ron emission t omography
(PET), beginning in t he mid-1980s[ 308] , and f unct ional magnet ic resonance
imaging (f MRI ), beginning in t he early 1990s[351, 407] . More w idespread lat er,
f ocused magnet ic st imulat ion, by t emporarily modif ying t he f unct ion of a
rest rict ed area of t he brain, became anot her pow erf ul inst rument t o clarif y
regional brain f unct ion[357, 393] . More recent ly, w hit e mat t er f iber t racking w it h
diff usion t ensor imaging—magnet ic resonance imaging (MRI ) t ract ography—is
adding t o our localizat ion t oolbox[72] . Alt hough anat omic measurement s used t o
be made w it h rat her simple t echniques in relat ively f ew individuals[175] , much
more sophist icat ed measurement s can now be perf ormed in large populat ions
using voxel-based morphomet ry and ot her comput er-aided t echniques[408] . This
edit ion of Local i zati on i n Cl i ni cal Neurol ogy ref lect s some of t he new insight s
int o cort ical localizat ion gained f rom t he use of t hese t echniques.
Anatomy of The Cerebral Hemispheres

The paired cerebral hemispheres derive f rom t he t elencephalon[58] . They are in
cont inuit y w it h t he diencephalon and are int erconnect ed by w hit e mat t er
commissures, including t he corpus callosum, t he ant erior and post erior
commissures, and t he commissure of t he f ornix. I n t he adult , t he cerebral
hemispheres, shaped like a cap, cover t he midbrain-diencephalic st ruct ures. A
midline sagit t al slit , t he longit udinal f issure, separat es t he t w o hemispheres.
Theref ore, each hemisphere has a larger l ateral aspect and smaller medi al and
i nf eri or aspects. Folds (gyri) and f urrow s (sul ci ) pat t ern t he surf ace of t he
cerebral hemispheres. The larger sulci (f i ssures) serve as anat omic landmarks
separat ing t he main regions of t he cerebral hemispheres.
O n t he l ateral aspect of each hemisphere, t w o large sulci separat e t he t hree
regions: the temporal l obe, inf erior t o t he Sylvian f issure; the f rontal l obe,
ant erior t o t he Rolandic or cent ral sulcus; and the pari etal l obe, post erior t o t he
Rolandic sulcus (Fig. 20-1A). The i nsul a lies buried in t he dept h of t he Sylvian
f issure. The most post erior port ion of t he lat eral aspect corresponds t o t he
occi pi tal l obe. An imaginary line, draw n f rom t he superior ext ent of t he pariet o-
occipit al sulcus in t he medial aspect of t he hemisphere t o a not ch in t he inf erior
aspect (preoccipit al not ch), const it ut es t he lat eral boundary bet w een t he
occipit al lobe and t he pariet al and t emporal lobes.
Tw o sulci running ant eropost eriorly divide t he f rontal l obe int o superi or, mi ddl e,
and i nf eri or f ront al gyri. Perpendicular t o t hese, and separat ed f rom t hem by t he
precent ral sulcus, lies t he precentral gyrus, w hich is just ant erior t o t he cent ral
sulcus. I n t he average healt hy person, but not in t hose w it h aut ism or ot her
development al language disorder, t he post erior part of t he t hird f ront al gyrus
(t riangular and opercular port ions) is larger in t he lef t hemisphere[110, 132] .
This diff erence is more pronounced in men[45] . Also,
t he lef t precent ral gyrus is t hicker t han t he right in right -handed men[11] . The
precent ral gyrus cont ains t he primary mot or area. Pri mary corti cal areas
const it ut e t he f irst areas of cort ex t o receive inf ormat ion f rom t he sense organs,
in t he case of t he primary sensory areas, or, in t he case of t he primary mot or
area, project s t o t he mot or nuclei of t he brainst em and spinal cord lodging t he
low er mot or neurons. The inw ard or out w ard project ions of t he primary cort ical
areas cont rast w it h t he rest of t he cort ex, named associ ati on cortex, giving rise
pref erent ially t o cort icocort ical connect ions.
FI G URE 20-1 Lat eral (A) and inf eromedial (B) view s of t he cerebral
hemispheres. The orbit al aspect s of t he f ront al lobes can be seen only in a
direct inf erior view, not show n in t his f igure. Depict ed, how ever, is t he
inf erior aspect of t he t emporal and occipit al lobes
Tw o t ransverse sulci divide t he temporal l obe int o superi or, mi ddl e, and i nf eri or
t emporal gyri. O n t he inf erior bank of t he Sylvian sulcus, t he transverse gyrus
(Heschl's) runs ant erolat erally over t he superior aspect of t he f irst t emporal
gyrus. I t const it ut es t he primary audit ory area and t he ant erior limit of t he
planum t emporale or suprat emporal plane, w hich, in t he average right -handed
person, is one-t hird larger in t he lef t hemisphere[175] (Fig. 20-2). Heschl's gyrus
is also larger on t he lef t , part icularly in men[184, 257] . Funct ional specializat ion
may explain t his f inding because in t he average person t here is an audit ory bias
t ow ard t he lef t hemisphere, such t hat , not only speech but also pure t ones
act ivat e Heschl's gyrus more on t he lef t t han on t he right hemisphere[124] .
Lat eralizat ion could begin in t he cochlea[430] . Addit ionally, individual anat omy
may det ermine or be det ermined by f unct ion. Normal individuals w ho analyze
musical sounds relying on spect ral pit ch rat her t han on f undament al pit ch have
relat ively larger right -sided Heschl's gyri[408] . This is t o be expect ed,
considering t hat t he lef t audit ory cort ex is relat ively specialized in rapid t emporal
processing, w hereas t he right audit ory cort ex show s a st ronger sensit ivit y f or
spect ral processing and a slow er t emporal processing mode[495] .
FI G URE 20-2 Exposed upper surf aces of t he t emporal lobes, show n in a

horizont al sect ion of t he brain. The area (planum t emporale, PT) limit ed
ant eriorly by t he t ransverse t emporal gyrus of Heschl (TG ) and post eriorly
by t he post erior ext ent of t he horizont al port ion of t he t emporal operculum
(PM) t ends t o be larger on t he lef t side. O t her relevant abbreviat ions: TP =
temporal pol e; O P = occi pi tal pol e. (Reproduced w it h permission f rom
G eschw ind N, Levit sky W. Human brain: lef t -right asymmet ries in t emporal
speech region. Sci ence 1968; 161: 186 . [175] Copyright 1969 by t he American
Associat ion f or t he Advancement of Science. )
Post erior t o t he Rolandic sulcus lies t he postcentral gyrus, separat ed f rom t he

rest of t he pari etal convexi ty by t he post cent ral sulcus. The post cent ral gyrus
houses t he primary somat osensory cort ex. The most inf erior ext ent of t his gyrus,
abut t ing t he Sylvian f issure, cont ains t he secondary somat osensory cort ex. A
t ransverse sulcus divides t he rest of t he pariet al lobe int o superi or and i nf eri or
pariet al lobules. Ant eriorly, t he inf erior pariet al lobule curves around t he
post erior ext ent of t he Sylvian sulcus (supramargi nal gyrus); post eriorly, around
t he post erior ext ent of t he superior t emporal sulcus (angul ar gyrus).
The medi al or mesi al aspect of t he cerebral hemisphere sw eeps around t he
corpus callosum and, post eroinf eriorly, blends rat her smoot hly w it h t he inf erior
aspect of t he hemisphere (Fig. 20-1B). Among t he major sulci in t he medial
aspect , t hree run radially and one runs parallel t o t he corpus callosum. The
lat t er, called t he ci ngul ate sul cus, separat es t he ci ngul ate gyrus, cent ripet al t o
it , f rom t he mesial aspect of t he f irst f ront al and paracent ral gyri. The mesial
aspect of t he f ront al and pariet al paracent ral gyri (paracentral l obul e) is w ell
demarcat ed f rom t he rest of t he mesial pariet al lobe (precuneus) by one of t he
t hree radial sulci, namely, t he marginal sulcus, w hich arises in t he cingulat e
sulcus. The ot her t w o radial sulci are more post erior. The large pariet o-occipit al
sulcus separat es t he pariet al precuneus f rom a mesial w edge of occipit al lobe
(cuneus), limit ed inf eriorly by t he calcarine sulcus. These t w o sulci meet
ant eriorly t o join t he post erior ext ent of t he cingulat e sulcus, w hich limit s
dorsally t he ist hmus of t he cingulat e gyrus as it sw eeps around t he post erior end
(spl eni um) of t he corpus callosum. As t he cingulat e gyrus courses
inf eroant eriorly around t he splenium, it blends w it h t he parahi ppocampal gyrus,
in t he most medial aspect of t he t emporal lobe. Hidden in t he recess bet w een
t he t emporal horn of t he lat eral vent ricle and t he lat eral aspect of t he midbrain,
t he hi ppocampal gyrus courses ant eriorly lat erosuperior t o t he parahippocampal
gyrus, separat ed f rom it by t he hippocampal sulcus. Ant eriorly, t hey converge
int o a small nub (t he uncus) t hat cont ains t he amygdalar nuclear complex.
The i nf eri or aspect of t he hemisphere comprises t he orbit al surf ace of t he f ront al
lobe and t he inf eromedial aspect s of t he occipit al and t emporal lobes (Fig. 20-
1B). A f ew irregular orbit al gyri and a medially locat ed st raight gyrus (gyrus
rectus), w hich lies medial t o t he olf act ory bulb and t ract , make up t he
orbit of ront al surf ace. The
demarcat ion bet w een t he t emporal and t he occipit al lobes is indist inct on t heir
inf erior aspect . A f usi f orm or occi pi totemporal gyrus, ant erolat erally, and a
l i ngual gyrus, post eromedially, can be dist inguished on t he sw at h t hat lies
bet w een t he collat eral sulcus (lat eral t o t he parahippocampal gyrus) and t he
inf erior t emporal gyrus.
FI G URE 20-3 The hist ologic appearance of t he f ive f undament al t ypes of
neocort ex, according t o von Economo[472] : 1 = agranul ar (pyrami dal ); 2 =
f rontal ; 3 = pari etal; 4 = pol ar; 5 = granul ar (koni ocortex). See t ext f or t he
names of layers I –VI
I n addit ion t o t he f ront al and t emporal lobe asymmet ries ment ioned in t he
preceding t ext , t he right f ront al lobe is of t en larger t han t he lef t , and t he lef t
occipit al lobe is larger t han t he right [184, 257] . Such anat omic asymmet ries
may ref lect t he localizat ion of language and ot her f unct ional specializat ion of
each cerebral hemisphere. I n general, t he right hemisphere is dominant f or t asks
requiring spat ial and const ruct ional skills, as w ell as f or direct ed at t ent ion and
body image, w hereas t he lef t hemisphere is dominant f or language and mot or
f unct ions, as w ell as linguist ic t hought and reasoning, analyt ic and mat hemat ical
skills, and t he t emporal sequencing of st imuli. The right hemisphere is also
dominant f or non-visuospat ial percept ion, including somest het ic, audit ory
(melody and t one discriminat ion), and emot ional f unct ions (e. g. , t he
comprehension of emot ional t one in voice and body gest ures).
The convolut ed pat t ern on t he surf ace of t he cerebral hemispheres emerges
during ont ogenesis t o accommodat e int o t he smallest volume t he large expansion
of cort ical gray mat t er (cortex) t hat charact erizes t he human brain. Six layers of
cells (neurons) can be dist inguished in most of t he cort ex (neocortex) (Fig. 20-
3). From surf ace t o dept h, t hey have been t ermed (I ) t he molecular layer, rich in
f ibers, (I I ) t he ext ernal granular layer, composed of small round or st ar-shaped
neurons, (I I I ) t he ext ernal pyramidal layer, cont aining medium-sized pyramidal
neurons, t heir larger apical dendrit es orient ed t ow ard t he surf ace, (I V) t he
int ernal granular layer, w hich, in addit ion t o small, round neurons cont ains a t hick
plexus of horizont ally direct ed f ibers, (V) t he int ernal pyramidal or ganglionic
layer, const it ut ed by t he larger pyramidal neurons, and (VI ) t he mult if orm layer,
made up of spindle-shaped neurons. Tw o small areas in t he inf eromedial aspect
of t he hemispheres have a simpler cort ex: t he olf act ory area (pal eocortex) and
t he hippocampal f ormat ion (archi cortex). Except f or t he primary visual cort ex in
binocular primat es, in w hich t his number is doubled, t he number of neurons in a
column (Fig. 20-3) t hrough t he dept h of t he neocort ex is t he same in diff erent
cort ical areas and in t he mammalian species[387] . I n humans, t he cort ex is

t hicker t o accommodat e t he same number of neurons t hat are f urt her spread
apart by t he richer net w ork of connect ions.
Alt hough it is six-layered t hroughout , t he neocort ex is not homogeneous. I n areas
t hat receive a heavy sensory project ion, t he granular layers are more bulky t han
t he pyramidal layers (granul ar cortex or koni ocortex, Fig. 20-3). The opposit e
holds t rue f or t he areas in w hich t he larger mot or project ions t o t he brainst em
and spinal cord originat e (agranul ar or pyrami dal cortex). Act ually, t he cort ex
may be parceled according t o t he cellular composit ion (cytoarchi tecture) of t he
various cort ical areas. Brodmann's cyt oarchit ect ural map (Fig. 20-4) depict s 50
areas[ 59] . Bet t er image processing t echniques combining hist ologic and “invivo”
imaging dat a and t he use of ot her cort ical markers, such as neurot ransmit t er
recept or densit y, herald t he arrival of more accurat e, comput er-guided,
probabilist ic maps of t he human cort ex [309, 406, 498] .
The cerebral hemispheres process int raindividual and ext raindividual inf ormat ion.
Most of t he lat t er input reaches t he primary cort ical areas t hrough t he t halamus.
I nf ormat ion concerning t he int erior homeost asis t ravels f rom t he brainst em and
hypot halamus t hrough t he medial t halamus, reaching mainly t he pericallosal,
mesial t emporal, insular, and orbit al cort ex (l i mbi c l obe). I n order t o act , bot h of
t hese syst ems need t o be “act ivat ed” by t he brainst em ret icular f ormat ion.
The main anat omic connect ions of t he cort ex are list ed in Table 20-1. I n
summary, t he ret ro-Rolandic port ion of t he cerebral hemispheres is chief ly
involved in t he processing of sensory inf ormat ion about t he out side w orld and
about t he mot or act s being perf ormed by t he individual. Bot h of t hese, but
part icularly t he lat t er, require t he int egrat ion of sensory inf ormat ion of diff erent
modalit ies (visual, somat osensory, et c. ). Lesions in t he “primary” sensory areas
cause loss of a specif ic sensory modalit y. These primary areas are list ed in
Table 20-1 ( Fig. 20-5). The cort ex surrounding t he primary sensory areas
processes t he modalit y-specif ic inf ormat ion and int egrat es it w it h inf ormat ion
f rom ot her sense organs and inf ormat ion about t he physiologic milieu of t he
individual.
Simply st at ed, t he cort ex adjacent t o t he primary sensory areas (secondary
sensory areas) processes unimodal sensory inf ormat ion, of t en keeping a
somat ot opic organizat ion, w hereas t he cort ex lying bet w een t he diff erent
secondary sensory areas (t ert iary sensory cort ex) int egrat es mult imodal sensory
inf ormat ion. For inst ance, somat osensory inf ormat ion reaches somat ot opically
t he post cent ral gyrus (Fig. 20-6), w hich project s somat ot opically t o t he superior
(arm and leg) and inf erior (head) pariet al lobules. Somat ot opic inf ormat ion is
int egrat ed w it h audit ory and visual inf ormat ion in t he inf eropost erior port ions of
t he inf erior pariet al lobule (angular gyrus)[ 298] and w it h visual and veget at ive
inf ormat ion in t he post eromedial port ions of t he pariet al lobe (precuneus).
Lesions of t he primary somat osensory area result in sensory loss, w hereas
lesions in t he mult imodal associat ion areas result in mot or perf ormances t hat
show t he lack of mult imodal int egrat ion. For inst ance, bilat eral lesions of t he
post erior port ion of t he superior pariet al lobule give rise t o t he impairment of
hand movement s under visual guidance[97] .
The act ivat ion of primary, secondary, and mult imodal sensory areas is highly
st imulus-specif ic and t ask-specif ic. For example, t he lef t post erior superior
t emporal gyrus is act ivat ed by acoust ic changes in speech as w ell as nonspeech
sounds, w hereas t he lef t supramarginal gyrus, a mult imodal associat ion area, is
more specif ically engaged in t he det ect ion of changes in phonological unit s, a
t ask t hat is mult imodal[77] . At t ent ion t o complex or nuanced sensory t asks, like
det ect ing a specif ic t arget syllable, enhances sensory perf ormance and requires
more cort ical act ivat ion[237, 478] . I t is likely t hat t his act ivat ion is accomplished
t hrough an at t ent ional net w ork described in more det ail lat er under t he sect ion
Di sturbances of Attenti on[ 326] . The cort ical areas of t he ret ro-Rolandic brain
t hat “gat e” t he act ivat ion of primary and secondary sensory areas are locat ed
around t he int rapariet al sulcus and in t he t emporo-occipit al region [129, 162,
221] . The pref ront al, insular, and cingulat e cort ex also modulat e t he act ivat ion of
sensory areas [85, 129, 388] .
The pre-Rolandic port ion of t he hemispheres cont ains programs concerned w it h
planning, init iat ion, and execut ion of movement s. The mesial f ront al cort ex
(cingulat e gyrus, Supplement ary Mot or Area [ SMA] ) is closely linked w it h t he
ret icular act ivat ing syst em and t he limbic lobe. I t appears t o mediat e t he drive t o
move in a meaningf ul direct ion (cort ical at t ent ion). Alt hough seemingly alert ,
pat ient s w it h large bilat eral lesions in t his region remain mot ionless and mut e
(akinet ic mut ism)[ 260] . From t he limbic syst em, inf ormat ion about past event s
and t heir bearing on t he w ell-being of t he individual reaches t he ant erior port ions
of t he f ront al lobe, w here it is int egrat ed w it h sensory inf ormat ion f rom t he
t halamus and f rom t he mult imodal associat ion areas of t he hemisphere.
Theref ore, t he best course of act ion w it hin a t emporal f ramew ork is delineat ed.
The f ront al cort ex rost ral t o
t he precent ral gyrus mediat es complex mot or programs, w hich are elicit ed under
t he “command” of t he mesial f ront al region and execut ed by w ay of t he
subcort ical nuclei (basal ganglia, brainst em nuclei) and primary mot or cort ex.
The primary mot or cort ex plays a great er role in t he execut ion of f ine, dist al
movement s, w hereas axial movement s, such as w alking, are mediat ed, t o a
great er ext ent , by subcort ical st ruct ures. The cerebellum and t he sensory nuclei
of t he brainst em, including t he vest ibular complex, provide t he mot or syst em w it h
essent ial f eedback inf ormat ion.
FI G URE 20-4 Brodmann's parcellat ion of t he lat eral (A) and medial (B)
aspect s of t he cerebral hemispheres according t o t he specif ic
cyt oarchit ect ure of each area[59]
This brief int roduct ion has at t empt ed t o highlight t he main f ramew ork of t he
incredibly complex
st ruct ure of t he cerebral hemispheres, w hich is st ill f ar f rom clear. Some
underst anding of t he anat omic st ruct ure f acilit at es t he ident if icat ion of t he most
likely locat ion of a cerebral hemispheric lesion based on it s clinical
consequences.
TABLE 20-1 Cerebral Hemispheric Connecti
Function Type Origin Cortical Area
Sensory areas
Piriform
(temporal uncus
Smell Olfactory bulb
and surrounding
cortex, area 28
Parainsular
Ventroposteromedial portion of
Taste
thalamic nucleus perietal
operculum
Vision
Lips of
Primary Lateral geniculate calcarine sulcus
visual area body (striate area,
area 17)
Striate area Parastriate
Secondary Lateral geniculate cortex (area 18)
visual area body Peristriate
Pulvinar cortex (area 19)
Auditory
Transverse
temporal gyrus
(Heschl), area
Primary Medial geniculate
41 (higher
auditory area body
frequencies
located more
medially)
Superior
Area 41 temporal gyrus
Secondary (area 22)
auditory areas
Parastriate
Area 8a
cortex (area 9)
Somatosensory
Primary
Postcentral
somatosensory
gyrus, first
areas
somatosensory
(receptors on
area
contralateral
(somatotopically
side of the organized, see
body or Fig. 20-6)
bilateral)
Muscle Ventral posterior

thalamic nuclei Area 3
spindles
Cutaneous
receptors for Areas 3b, 1
“texture”
Deep tissue
(joints,
aponeuroses), Area 2
“shape”
discrimination
Second
somatosensory
Thalamus area (upper
Painful
(ventrobasal nuclear back of Sylvan
stimuli
complex) fissure,
adjacent to the
insula)
Areas 2 and 5
Superior
Second Superior portion parietal lobule
somatosensory (leg, trunk, arm) Supramarginal
areas gyrus
Inferior portion

(neck, head)
Angular gyrus
Posterior
cingulate gyrus
Precuneus
(area 23)
Peristriate belt
(area 19)
Tertiary
somatosensory
areas (cortical
Precuneus
sensory
Peristriate belt
convergence
(area 19)
zones)
Posterior
portion of
Angular gyrus
superior and
middle temporal
gyri
Inferomedial
temporal cortex
Motor areas
Thalamus (VL) (from

cerebellum and
basal ganglia) Precentral
Somatosensory gyrus (area 4),
Primary motor
areas somatotopically
area
Supplementary organized (see
motor area (mesial Fig. 20-6)
frontal)
“Premotor” cortex
Precentral gyrus
(area 4)
First and second
Supplementary Supplementary
primary
motor area motor areas
somatosensory
areas
Cingulate gyrus
Foot of the
Frontal eye Peristriate cortex
middle frontal
fields (area 19)
gyrus (area 8)
Multimodal parieto-
occipito-temporal
areas (angular “Premotor”
Secondary
gyrus, precuneus) frontal cortex
association
“Prefrontal” areas, (areas 6, 8, 9,
motor areas
orbitofrontal cortex 44, 45)
Anterior cingulate
gyrus (area 24)
Anteromedial
thalamus
Temporal pole
Tertiary “Prefrontal
Anterior portion of
association cortex” (areas
cingulate gyrus
motor areas 9, 10, 11)
(area 24)
Angular gyrus
Precuneus
Areas involved in mnestic processes

Association motor
and sensory areas
Medial thalamus Temporal lobe
Medial
hypothalamus
Symptoms and Signs Caused by Cerebral Hemispheric

Lesions
Lesions of t he phylogenet ically most recent part of t he cent ral nervous syst em
diff er in t heir manif est at ions f rom t hose t hat aff ect more primit ive levels.
Theref ore,
1. The great er plast icit y of t he hemispheres, mediat ed by t he large number of

cort ical neurons, and t he exist ence of redundant pat hw ays result in l ess
pronounced def i ci ts w it h lesions t hat , had t hey aff ect ed a similar volume of
t he brainst em or spinal cord, w ould have caused a major mot or or sensory
dist urbance[ 86, 142] . Plast icit y and redundancy also explain t hat dest ruct ion
of cort ical areas t hat are act ivat ed by a specif ic t ask on f unct ional
neuroimaging may not cause last ing clinical f indings relat ed t o t hat t ask
unless t he lesion is relat ively large[143, 466] .
2. The neurologic def icit caused by cerebral hemispheric lesions t ends t o be

more i nconsi stent t han def icit s relat ed t o lesions in t he low er echelons of t he
nervous syst em. Reduced at t ent ion, w hich may be relat ed t o t he t ime of t he
day, a noisy environment , or lack of adequat e st imuli, is only one of t he many
f act ors t hat can inf luence t he out come of a given neurologic examinat ion.
Typical of part ial mult imodal def icit s, such as aphasia, is t hat t he pat ient
comes up periodically w it h t he correct perf ormance, leaving t he junior
clinician w ondering about t he ext ent of t he pat ient 's def icit . Repeat ed
int erview s minimize t his problem and allow t he examiner t o arrive at a much
more accurat e pict ure of t he nat ure, and t heref ore t he localizat ion, of t he
pat ient 's dist urbance. O f course, t he luxury of repeat ed examinat ions is
unaff ordable w hen a quick decision has t o be reached in an emergency
management sit uat ion, but it should be available w hen planning t he long-t erm
management and rehabilit at ion of t hese pat ient s.
3. When obt aining t he hist ory pert inent t o a cerebral hemispheric lesion, t he
examiner must realize t hat the pati ent i s of ten unaware of the extent of the
def i ci t, part icularly w hen it involves complex (mult imodal) behavior (aphasia,
apraxia). Pat ient s w it h right -hemisphere lesions t end t o be impervious t o
t heir def icit more of t en t han pat ient s w it h lef t -hemisphere lesions. Ant on's
syndrome, in w hich t he pat ient denies an ot herw ise obvious blindness t hat is
relat ed t o a cort ical pariet o-occipit al lesion, is only one inst ance of such lack
of insight . Somet hing similar occurs w it h ot her hemisphere-relat ed sensory
def icit s. The ext ent and qualit y of t hese def icit s are less precise t han w hen
t he sensory loss is caused by lesions in more element ary st ruct ures of t he
nervous syst em, such as t he brainst em or a sensory peripheral nerve. Most
pat ient s w it h an ulnar neuropat hy can out line a precise area of numbness in
t he medial aspect of t heir hands. By cont rast , a pat ient w it h a hemispheric
lesion, even aff ect ing t he primary
somat osensory cort ex of t he post cent ral gyrus, may have a diff icult t ime
localizing t he area of sensory loss. This charact erist ic of hemispheric
lesions, combined w it h t he diff icult y of elicit ing all t he def icit s in a short
int erview, make it of t en necessary t o obt ain inf ormat ion f rom people w ho
know t he pat ient w ell t o localize a cort ical lesion correct ly.
4. For adequat e localizat ion, mul ti modal def i ci ts, such as alexia, must be
anal yzed. The pat ient may be unable t o underst and w rit t en mat erial because
his saccades t o t he lef t side are incomplet e, leading him t o miss t he
beginning of w ords and sent ences (right f ront opariet al lesion), or because he
cannot grasp t he meaning of an array of st rokes t hat make up a w rit t en w ord
(lef t occipit al lesion). I t behooves t he examiner t o go beyond t he obvious
dist urbance and t ry t o underst and it s st ruct ure and t he primary def ect
responsible f or it .
5. The same f unct ion is represent ed in various areas of t he cort ex or even in
cont ralat eral hemispheres in diff erent pat ient s. This i ndi vi dual vari abi l i ty
makes t he localizat ion of hemispheric disease part icularly t axing. The most
common anat omic correlat ions of clinical signs and sympt oms are described
in t he subsequent t ext , but any at t empt t o pinpoint t he exact square
cent imet er of t he cort ex t hat account s f or a def icit in a part icular pat ient is a
f ut ile endeavor. Likew ise, ident if icat ion of t he area of t he cerebral
hemispheres most likely t o be injured in t he cont ext of a set of sympt oms
and signs does not mean t hat t he f unct ion lost “is localized” in t hat area of
t he brain. Most cort ical f unct ions are subserved by ext ensive net w orks.
Funct ional neuroimaging may be used t o help def ine some of t he f unct ions
likely t o be impaired in an individual if a part of t he cort ex is lesioned, f or
inst ance, in t he course of surgery t o remove a t umor or an epilept ogenic
area[ 272, 380] .
6. Because most hemispheric f unct ions are subserved by ext ensive net w orks,
of t en complement ary and redundant , si ngl e l esi ons may be cl i ni cal l y si l ent
and become sympt omat ic w hen addit ional lesions impair t he f unct ion of t he
net w ork[ 467] . Mult iple lesions may occur simult aneously or separat ed by any
lengt h of t ime.
7. For t he sake of rat ionalizat ion, t he complex and f luid clinical pict ure
displayed by pat ient s w it h cerebral lesions has been compart ment alized int o
syndromes. I t should be realized, how ever, t hat of t en t he di f f erence between
syndromes i s merel y one of degree. A similar amount of t issue loss
underlies t he global aphasia t hat a pat ient has a f ew days af t er inf arct ion
and t he Broca (mot or) aphasia t hat event ually develops some mont hs lat er.
Also, init ially t he localizat ion of t he def icit is compounded not only by edema
and met abolic abnormalit ies at t he sit e of t he lesion but also by dysf unct ion
(diaschisis) of areas of t he brain aw ay f rom t he primarily damaged region,
part icularly t hose heavily int erconnect ed w it h it , such as t he homologous
area of t he cont ralat eral hemisphere[216, 270] .
8. Lesions t hat aff ect t he same port ion of t he cerebral hemispheres may
present very diff erent clinical pict ures depending on t he tempo and nature of
the damage. Sudden, “t hrough” lesions, such as inf arct s t hat dest roy all t he
neurons in a port ion of t he cort ex, t end t o cause a more severe def icit t han
t umors t hat slow ly inf ilt rat e t he same area of t he brain. For inst ance, small
inf arct s of t en cause aphasia, but t umors have t o be quit e large bef ore t hey
cause an aphasic syndrome. Weakness may be rat her prof ound af t er a small
inf arct , but a t umor seldom causes severe w eakness unt il it ext ensively
involves a cerebral
hemisphere. Theref ore, localizat ion f or diff use lesions is less accurat e.
Because of t he plast icit y of t he hemispheres, how ever, as t ime elapses af t er
an acut e, “t hrough” lesion, it s clinical manif est at ions may resemble t hose of
an inf ilt rat ive lesion of t he same area. Rat her t han being rest rict ed t o a lobe
or gyrus, many pat hologic processes (e. g. , Alzheimer's disease,
encephalit is) aff ect t he hemispheres in a diff use or disseminat ed f ashion. A
combinat ion of def icit s, w hich are predominant ly manif est at ions of bilat eral
damage t o t he mult imodal associat ion cort ex, t hen const it ut es t he clinical
present at ion. I n t hese inst ances, neuroimaging f indings are part icularly
helpf ul t o t ry t o correlat e f unct ional def icit s w it h regional brain anat omy or
f unct ion. For inst ance, t he clinical variet ies of primary progressive aphasia
correspond t o at rophy of relat ively specif ic areas of t he lef t perisylvian
cort ex[ 185] .
9. Cort ical plast icit y result s in a more compl ete recovery f rom element ary
neurologic def icit s, such as w eakness or numbness, alt hough more complex
mot or or sensory def icit s may remain. At t he bedside or in a quick off ice
visit , t hese are more diff icult t o det ect t han element ary def icit s, alt hough
t hey may be very disrupt ive t o t he pat ient 's prof essional and f amily lif e[181] .
Funct ional recovery f ollow ing cort ical lesions or development al disorders is
mediat ed by f unct ional reorganizat ion of t he cort ex, w here a sound cort ical
area, eit her in t he same or opposit e hemisphere assumes t he f unct ions
f ormerly subserved by t he lesioned area [65, 133, 160, 258, 488] .
Part icularly w it h subcort ical lesions, t he new ly responsible cort ical area is
generally larger t han t he original one, at least short ly af t er t he insult ,
possibly ref lect ing a less eff icient neuronal net w ork[291] . The area of
act ivat ion shrinks as t raining progresses and t he def icit improves[477] .
How ever in some inst ances act ivit y in t he cont ralesional hemisphere may
seem t o int erf ere w it h t he f unct ional recovery, suggest ing t he need f or new
rehabilit at ion paradigms[338] .
10. Because cort ical plast icit y is mediat ed by ext ensive mult isynapt ic arrays,
w hich are suscept ible t o metabol i c di sturbances t hat int erf ere w it h t he
elaborat ion and processing of neurot ransmit t ers, t oxic met abolic insult s
aff ect ing t he w hole brain impair part icularly t he f unct ions new ly acquired in
t he process of “repair” of a f ocal lesion[147] . Theref ore, t hey may again
bring about a clinical def icit t hat had been w ell compensat ed. For inst ance, a
pat ient w it h a mild residual diff icult y in naming object s f ollow ing a large
lesion of t he dominant t emporal lobe, w hich init ially caused a severe sensory
aphasia, may again become unable t o underst and conversat ional speech
w hen suff ering a bout of pneumonia.
11. Lesions t hat aff ect t he cort ex select ively (e. g. , hypoxic laminar necrosis)
give rise t o a clinical pict ure t hat diff ers f rom lesions circumscribed t o t he
w hit e mat t er (e. g. , mult iple sclerosis).
A. Charact erist ic of corti cal l esi ons are (a) seizures and (b) mult imodal
mot or and sensory def icit s, such as aphasia and apraxia. Alt hough
subcort ical lesions may cause aphasic sympt oms, t hese are seldom as
pronounced or long last ing as t hey are w it h cort ical lesions.
B. Charact erist ics of whi te matter l esi ons are (a) w eakness, (b) spast icit y,
(c) visual f ield def icit s, (d) “pure” mot or syndromes, and (e) urinary
incont inence. Lesions t hat involve t he w hit e mat t er of t he hemispheres
cause sympt oms t hat are ref erable t o t he cort ical region giving rise t o
t he w hit e mat t er t ract involved.
12. More t han any ot her part of t he nervous syst em, t he cerebral hemispheres
are amenable t o t he localizat ion of lesions provided by neuroi magi ng,
including comput ed t omography (CT) scan and MRI [310] . PET and single
phot on emission comput ed t omography (SPECT) depict not only t he primary
anat omic lesion but also met abolic or perf usion change in areas f unct ionally
relat ed t o it (diaschisis). The ext ent of changes on PET or SPECT of t en
correlat e bet t er w it h t he severit y of clinical sympt oms and signs t han t he CT
scan or MRI abnormalit ies[266, 327] . The clinical evaluat ion of a pat ient w it h
a cerebral hemispheric lesion is st ill paramount f or a lucid management plan.
Lesions as common as brain inf arct s may remain invisible on CT scan f or
some t ime af t er t he ict us or may pass unnot iced alt oget her if t hey are
rest rict ed t o t he cort ex or cause coagulat ive necrosis. Diff usion-w eight ed
MRI depict s t hem earlier and provides inf ormat ion on t he t iming of t he
lesion[ 218] . Tumors are easily det ect ed on CT scan or MRI , but disorders
such as Alzheimer's disease cause more subt le f indings on t hese
neuroimaging modalit ies. Alt hough t here are quit e specif ic st ruct ural and
met abolic changes in samples of pat ient s w it h Alzheimer's disease, a single
neuroimaging
st udy st ill does not provide t he diagnosis in t he individual pat ient [305] .
Cort ical lesions giving rise t o f ocal epilepsy, or w hit e mat t er lesions in
mult iple sclerosis, are more of t en evidenced by MRI t han CT scan, but t hey
occasionally remain undiscovered[301, 395] . Finally, a good underst anding of
t he anat omic correlat ion of behavioral sympt oms allow s t he clinician t o
correlat e t he neuroimaging f indings w it h t he present ing complaint s, t hereby
avoiding t he mist ake of managing as an act ive lesion one t hat bears no
relat ion t o t he present illness (such as hydrocephalus in a pat ient w it h
Alzheimer's disease), or of having a f alse sense of securit y w hen a negat ive
scan f ails t o disclose an act ive lesion (such as in mult iple sclerosis).
FI G URE 20-5 Dist ribut ion on t he lat eral (A) and medial (B) aspect s of t he
cerebral hemispheres of t he f ive f undament al t ypes of cort ex show n in Figure
20-3. Type 1 (pyramidal) is depict ed in w hit e and t ype 5 (granular) is
depict ed t he darkest . Not e t hat t he primary sensory areas, including t he
audit ory (t ransverse t emporal gyrus of Heschl), visual (calcarine cort ex), and
somest het ic (post cent ral gyrus) areas have granular cort ex. Associat ion
cort ex spraw ls among t hem. (Corresponds t o Figures 70 and 71 f rom von
Economo[ 472] . )
FI G URE 20-6 Cort ical represent at ion (according t o Penf ield and
Jasper[ 362] ) of t he diff erent part s of t he body in t he peri-Rolandic mot or and
sensory areas. The f ront al pole of t he brain is represent ed in t he lef t port ion
of t he f igure
Because t he out put of t he brain is ult imat ely a mot or out put , no mat t er w here in
t he cerebral hemispheres a lesion has occurred, t he physician becomes aw are of
it by observing t he pat ient 's mot or perf ormance. Such a mot or perf ormance
depends on (a) t he pat ient 's level of alert ness, mediat ed by t he ascending
ret icular act ivat ing syst em (ARAS); (b) t he abilit y t o concent rat e on a t ask
(cort ical at t ent ion); (c) t he percept ion of sensory st imuli and of t heir relat ion t o
past experiences; and (d) t he abilit y t o carry out t he sequence of movement s
t hat makes up t he mot or act it self , w het her it be a handshake or an oral account
of t he current illness. Hemispheric lesions can dist urb any or several of t he last
t hree st eps. The result ing disorders are considered successively (Table 20-2).
Disturbances of Attention
At t ent ion may be def ined as t he w aking st at e in w hich sensory or mnest ic
inf ormat ion is select ively perceived, allow ing t he coherent perf ormance of
planned mot or behavior. This select ivit y is associat ed w it h unaw areness of a
great deal of irrelevant st imuli and memories. I t result s f rom act ive neural
f acilit at ory and inhibit ory processes t aking place at various levels of t he nervous
syst em, f rom t he peripheral sense organs t o t he cort ex. Alt hough at t ent ion
requires a cert ain level of alert ness, alert ness is not alw ays associat ed w it h
at t ent ion. Such is t he case of t he akinet ic mut e st at e, in w hich t he pat ient
appears alert , yet lies immobile and mut e, alt hough his eyes dart in t he direct ion
of any novel st imulus. Alert ness, w hich precedes at t ent ion, can be nonspecif ic
(such as in t he alert ing react ion t hat occurs w hen a person adopt s an
explorat ory at t it ude t o t he immediat e environment , becoming recept ive t o a great
deal of st imuli) or specif ic (w hen t he meaning of t he most signif icant st imulus is
recognized and alert ness is specif ically and st eadily direct ed t ow ard it ). The
lat t er is more properly called attenti on. O n t he basis of it s origin, at t ent ion may
be “passive” (involunt arily t riggered by ext ernal st imuli and basic drives) or
“act ive” (volunt arily generat ed and direct ed). Act ive at t ent ion is mediat ed by a
dorsal syst em including t he superior pariet al lobule and t he superior port ion of
t he dorsal pref ront al cort ex[86] . Bot h hemispheres part icipat e in act ive or goal-
direct ed at t ent ion. By cont rast , t he syst em act ivat ed by ext ernal st imuli is
lat eralized t o t he right hemisphere, part icularly in right -handed individuals[153] .
I nst ead of being dorsal, as t he act ive one, it involves t he cort ex of t he inf erior
pariet al lobule, t he post erior port ion of t he superior t emporal gyrus, and t he
inf erior port ion of t he pref ront al cort ex[86] . This alert ing net w ork seems t o
int errupt ongoing cognit ive act ivit y w hen a st imulus t hat might be import ant is
det ect ed. Since t he right hemisphere provides alert ing mechanisms f or bot h
sides of t he body, at t ent ional impairment occurs more of t en and is more
pervasive w it h right -sided hemispheric lesions.
Cort ical alert ing mechanisms are act ivat ed by brainst em st ruct ures. The
mesencephalic ret icular f ormat ion project s t o t he cort ex in a diff use polysynapt ic
f ashion, w it h t his project ion likely t raveling t hrough t he t halamus or t he basal
f orebrain [209, 443] . St imulat ion of t he mesencephalic ret icular f ormat ion is
associat ed w it h arousal, bilat eral dest ruct ion of t he mesencephalic ret icular
f ormat ion result s in coma, and unilat eral lesions of t he mesencephalic ret icular
f ormat ion result in cont ralat eral inat t ent ion, probably due t o unilat eral
hypoarousal of t he hemisphere[209, 481] . The mesencephalic ret icular f ormat ion
also f acilit at es t he relay of sensory inf ormat ion t o t he cort ex by inhibit ing t he
nucleus ret icularis t halami, w hich, in t urn, project s t o and inhibit s t he t halamic
relay nuclei. Theref ore, t he t ransmission of sensory dat a t hat are relayed
t hrough t he specif ic t halamic nuclei t o t he cerebral cort ex is enhanced by
mesencephalic ret icular st imulat ion (or behavioral arousal), and unilat eral
mesencephalic ret icular lesions may cause neglect because t he t halamic sensory
nuclei are being inhibit ed by t he nucleus ret icularis t halami[209] . Dorsal
mesencephalic lesions may cause cont ralat eral visual “inat t ent ion” by int errupt ing
uncrossed pat hw ays f rom t he superior colliculus t o t he dorsolat eral pref ront al
cort ex[ 171] .
The primary sensory cort ex cont ribut es import ant ly t o at t ent ional mechanisms,
part icularly by signaling st riking or salient sensory st imuli [316, 350] .
Primary sensory cort ical areas (e. g. , f or vision, Brodmann area 17) project t o
neighboring modalit y-specif ic cort ical areas, f or inst ance, in t he case of vision,
Brodmann area 18. Modalit y-specif ic areas project in t urn t o t he mult imodal
associat ion cort ex of t he pariet ot emporal lobes. Mult imodal sensory areas
combine inf ormat ion f rom vision, hearing, and somat osensory st imuli. Modalit y-
specif ic associat ion areas may det ect st imulus novelt y and, by cort icof ugal
pat hw ays t hat inhibit t he nucleus ret icularis t halami, pot ent iat e t halamic relay of
sensory inf ormat ion. Mult imodal sensory areas may also be import ant in
det ect ing st imulus novelt y and signif icance. I n cont rast t o unimodal associat ion
cort ex, w hich project s t o specif ic part s of t he nucleus ret icularis t halami and
t hereby gat es sensory input in one modalit y, mult imodal areas inhibit t he act ion
of t he nucleus ret icularis t halami in a more general f ashion, providing f urt her
cort ical arousal. The mult imodal sensory areas may also project direct ly t o t he
mesencephalic ret icular f ormat ion t o inf luence arousal, alt hough some
experiment s show a more import ant role of modalit y-specif ic areas f or
at t ent ional mechanisms[79] .
TABLE 20-2 Clinical M anifestations Of Cerebral

Hemispheric Lesions
1. Attentional disturbances
1. Unilateral inattention
1. Sensory (attentional deficit)
1. Unimodal (double simultaneous stimulation)
2. Multimodal
2. Motor (intentional disorder or hemiakinesia)
2. Nonspatial inattention
1. Motor or verbal impersistence
2. Motor or verbal perseveration
3. Echolalia, echopraxia
4. Akinetic mutism
5. Intrusions
1. Verbal
2. Motor
2. Emotional disturbances
1. Due to diencephalic or brainstem lesions
(accompanying somnolence, rage or fear of
hypothalamic origin, or amnesia)
2. Distorted perception of noxious stimuli
1. Blunted (cingulated gyrus, temporal tip)
2. Heightened (septal region)
3. Distorted perception of other sensory stimuli
1. Blunted
1. W ernicke's aphasia
2. Sensory aprosodia
2. Heightened
1. Delusions
2. Perception without object (hallucinations)
4. Distorted perception of social nuances
1. Blunted (frontal)
2. Heightened (temporal)
5. Distorted motor expression of emotions
1. Hypokinesia; motor aprosodias (frontal, right
hemisphere)
2. Hyperkinesia, including agitated delirium
(mesial temporo-occipital)
3. Uninhibited emotional expression. Pathologic
laughter and crying (bilateral corticobulbar
tract)
3. Memory disturbances
4. Sensory disturbances
1. Smell
2. Taste
3. Vision (calcarine cortex, visual association
cortex, multimodal cortex)
1. Hallucinations
1. Simple
2. Complex
2. Visual agnosia
1. Apperceptive
2. Associative
3. Color blindness (achromatopsia)—color
agnosia
4. Prosopagnosia
5. Landmark agnosia
6. Visual simultanagnosia (Balint's syndrome)
3. Alexia
1. Pseudoalexia
2. Literal alexia
3. Alexia without agraphia
4. Alexia with agraphia
4. Visual anosognosia
1. Unilateral–hemianopic anosognosia
2. Bilateral–denial of blindness (Anton's
syndrome)
4. Auditory information (primary auditory area and
association cortex of the temporal lobe and
inferior parietal lobule)
1. Hallucinations
2. Auditory agnosia
3. Pure word deafness
4. Sensory amusia
5. Sensory (posterior) aphasias
1. W ernicke's aphasia
2. Conduction aphasia
3. Transcortical sensory aphasia
4. Semantic anomia
5. W ord-selection anomia
5. Somatosensory perception
1. Simple somatosensory disturbances
1. Decreased perception
2. ldquo;Increased” perception, objectless
perception (paresthesias)
2. Complex somatosensory disturbances
1. Disturbances in “body schema” and spatial
relationships
1. Nondominant hemisphere
1. Anosognosia
2. Autotopagnosia
3. Spatial disorientation
4. Hemispatial neglect
5. Constructional apraxia
6. Dressing apraxia
7. Loss of topographical memory
8. Allesthesia
9. Hemisomatognosia
10. Asymbolia for pain
2. Dominant hemisphere
1. Finger agnosia
2. Right–left disorientation
2. Somatosensory varieties of agraphia
3. Somatosensory varieties of acalculia
5. Disturbances of sensorimotor integration and
movement execution (parietal, frontal)
1. Apraxia
1. Parietal apraxia
2. Callosal apraxia
3. Frontal apraxia
4. Apraxia of gait
5. Limb-kinetic apraxia
2. Other disturbances of limb or face movements
1. ldquo;Pyramidal” weakness
2. Paratonia (“Gagenhalten”)
3. Primitive reflexes
1. Grasp
2. Palmomental
3. Sucking, snout, rooting
4. Corneomandibular
4. Opercular syndrome, pseudobulbar palsy
3. Ocular motor disturbances
1. Supranuclear gaze palsy
2. Lateral eye deviation on forcible lid closure
3. Gaze apraxia (Balint's syndrome)
4. Motor disturbances of goal-oriented behavior
1. Motor (anterior) aphasias
1. Pure word anarthria (phonetic disintegration
syndrome)
2. Broca's aphasia
3. Transcortical motor aphasia
2. Pure agraphia
5. Disturbances of goal-oriented behavior
6. Environmental dependency syndrome—imitation
and utilization behavior
6. Disturbances related to interhemispheric
disconnection (callosal syndrome)
1. Lack of kinesthetic transfer
1. Inability to mimic position of the contralateral
hand
2. Left-hand agraphia; left-hand apraxia
3. Right hand constructional apraxia
4. Intermanual conflict (alien left hand)
2. Perplexity (and confabulation) elicited by right-
hand activity
3. Double hemianopia
7. Dementia
Brain regions t hat part icipat e in at t ent ional mechanisms can be separat ed int o
t w o broad cat egories: act ivat ed sensory areas and t he brain st ruct ures t hat
act ivat e t hem. Areas of sensory cort ex are act ivat ed, w hich are relevant in a
given moment . For inst ance, w hen at t ending t o t he color of an object , t he lingual
gyrus, cont aining secondary visual associat ion cort ex, is act ivat ed[55] . The
act ivat ing st ruct ures f orm a net w ork of dist ribut ed processing, w it h nodes t hat
play a larger role in one or anot her area of at t ent ional mechanisms. As Mesulam
has put it , t he inf erior pariet al lobule sculpt s t he subject ive at t ent ional
landscape, w hereas premot or areas of t he f ront al lobe plan t he st rat egy f or
navigat ing it [324, 325] . The cingulat e gyrus det ect s conf lict ing processes during
t ask perf ormance t hat might be associat ed w it h errors[68, 71] . I t may inject int o
t he at t ent ional net w ork t he relevance f or survival of a part icular sit uat ion. A
post erior t emporo-occipit al area seems t o mediat e t he shif t of t he at t ent ional
f ocus across t he visual scene[178] . Act ivat ion of t hese cort ical areas requires
input f rom t he basal ganglia t hrough t he t halamus. I n addit ion t o relaying t o t he
cort ex sensory and basal ganglionic inf ormat ion, t he t halamus plays a key role in
at t ent ional mechanisms, not only t hrough t he ret icular nucleus but also t hrough
t he pulvinar, heavily connect ed t o t he pariet al and f ront al at t ent ional areas. All
t hese anat omic st ruct ures, int erconnect ed t o each ot her, w ork in unison t o
provide t he complex mechanisms involved in maint aining at t ent ion (Fig. 20-7).
Lesions of any of t he component s of t he result ant net w ork or t heir
int erconnect ions, including t he f iber bundles in t he hemispheric w hit e mat t er, can
result in neglect [324, 325] . For inst ance, disrupt ion of t he superior
occipit of ront al f asciculus, a poorly
know n pariet al–f ront al pat hw ay, causes neglect in humans[454] . Neglect
result ing f rom unilat eral post erior pariet al lesions is charact erized most ly by
sensory ext inct ion, w hereas neglect associat ed w it h f ront al or basal ganglionic
lesions includes a disrupt ion of explorat ory and orient ing movement s t ow ard t he
neglect ed hemispace[94, 434] .
FI G URE 20-7 Represent at ion of some syst ems t hat play an import ant role in
at t ent ion and arousal. NR = nucl eus ret icularis t halami; MRF =
mesencephal i c ret icular f ormat ion; VPL = ventral post erolat eral nucleus of
t halamus; MG = medi al geniculat e; LG = l ateral geniculat e. (Adapt ed f rom
Heilman KM, Valenst ein E, Wat son RT. Neglect . I n: Asbury AK, McKhann G M,
McDonald WI , eds. Di seases of the nervous system. Cl i ni cal neurobi ol ogy.
2nd ed. Philadelphia, PA: WB Saunders, 1992: 768–779. )
St imulus signif icance is det ermined by t he needs of t he organism. The limbic

syst em, closely relat ed t o t he hypot halamus and ot her areas import ant f or t he
maint enance of homeost asis, and t he f ront al lobes, crit ical f or t he evaluat ion and
planning of a f ut ure course of act ion, are import ant in st imulus processing. Not
surprisingly, t he inf erior pariet al lobe has prominent connect ions w it h t he f ront al
lobe and cingulat e gyrus [209, 210, 483] .
Disorders of at t ent ion due t o hemispheric lesions may aff ect t he pat ient 's
behavior t ow ard event s in one side of t he personal and ext rapersonal space
(hemi -i nattenti on, or spati al i nattenti on) or nonspat ial cognit ive f unct ions.
Unilateral Inattention
Unilat eral inat t ent ion or neglect is charact erized by one or more of t he f ollow ing
f indings: (a) hemi -i nattenti on, w hich is t he pat ient 's lack of orient ing responses
t o unilat eral novel st imuli (audit ory, visual, or t act ile) in t he absence of a primary
sensory or mot or def icit t hat could explain such behavior[209] , (b) exti ncti on on
double simult aneous st imulat ion, t est ed most of t en w it h t act ile or visual st imuli
t hat t he pat ient perceives on t he aff ect ed side on single, but not on simult aneous
st imulat ion of bot h sides, (c) hemi aki nesi a or mot or neglect , w hen t he pat ient
t ends t o direct all his or her act ivit y t o one hemispace, (d) al l esthesi a, w hen
cont ralesional st imuli are at t ribut ed t o t he ipsilat eral side. Alt hough f requent ly
associat ed, t hese def icit s result f rom damage t o diff erent port ions of t he
at t ent ional net w ork, and t heref ore some but not ot hers may be seen in a given
pat ient [ 446] . Anosognosi a, et ymologically, lack of aw areness of disease and, in
t his case, of neurologic impairment , is of t en seen w it h right -hemispheric
lesions[ 134] . How ever, it need not be associat ed w it h a neglect syndrome and
of t en it is not [446] . Neglect may be primarily sensory (attenti onal def ect) or
primarily mot or (i ntenti onal di sorder or hemi aki nesi a)[ 209] .
Sensory Inattention
Sensory inat t ent ion may be uni modal (e. g. , visual inat t ent ion), in w hich case
st imuli of a specif ic sensory modalit y are less w ell perceived on one side. Most
commonly, t hese pat ient s have ext inct ion t o double simult aneous st imulat ion,
f ailing t o report st imuli delivered t o t he side cont ralat eral t o t he lesion. This
clinical f inding may be explained because st imuli f rom one side of t he body
compet e w it h st imuli f rom t he cont ralat eral side f or cort ical act ivat ion[148] .
How ever, cort ical act ivat ion of t he aff ect ed hemisphere may be present even
w hen t he pat ient does not see a visual st imulus in t he aff ect ed hemispace[379] .
I n a given pat ient , it may be diff icult t o dist inguish
bet w een hemianest hesia or hemianopia and severe somest het ic or visual hemi-
at t ent ion. O ccasionally, visual inat t ent ion may be dist inguished f rom hemianopia
by changing t he hemispace of present at ion[256] . For inst ance, a pat ient w ho
could not det ect single st imuli present ed in t he lef t visual f ield w hen t he eyes
w ere direct ed st raight ahead (midsagit t al plane) or t ow ard t he lef t hemispace
could det ect st imuli in t he same ret inot opic posit ion w hen t he eyes w ere direct ed
t ow ard t he right hemispace, so t hat t he lef t visual half -f ield w as in t he right
hemispace[ 256] . This pat ient had hemispat ial visual inat t ent ion masquerading as
hemianopia.
Cont ralat eral inat t ent ion occurs most commonly w it h lesions of t he inf erior
pariet al lobule but may also occur w it h lesions of t he t emporopariet al–occipit al
junct ion, dorsolat eral f ront al lobe, cingulat e gyrus, insular cort ex, t halamus, and
mesencephalic ret icular f ormat ion [97, 209, 292, 293, 479, 480, 481] . These
areas have show n act ivat ion in at t ent ional t asks [71, 129, 178, 221, 431] .
Whereas unilat eral lesions of t he primary cort ex cause cont ralat eral unimodal
sensory loss, lesions of unimodal associat ion cort ex impair t he percept ion of
cont ralat eral versus ipsilat eral st imuli of t hat modalit y. For example, lesions
aff ect ing areas 18 and 19 (t he associat ion areas of vision) in t he pariet o-
occipit al region cause t he ext inct ion of a cont ralat eral visual st imulus on bilat eral
visual st imulat ion. Lesions in t he ant erior associat ion areas of t he pariet al lobe
(t he associat ion area f or sof t t ouch) cause cont ralat eral ext inct ion of double
simult aneous t act ile st imuli[209] .
The ot her and more common variet y of unilat eral sensory inat t ent ion i s
mul ti modal . These pat ient s neglect t he hemispace cont ralat eral t o t he lesion
w hen perf orming complex t asks such as dressing, in w hich t hey may f ail t o cover
t he neglect ed side (dressing apraxia), or draw ing, in w hich element s of a pict ure
may be placed in an abnormal spat ial relat ionship t o one anot her (const ruct ional
apraxia). Pat ient s w it h personal inat t ent ion may deny t hat t heir ow n limbs belong
t o t hem or may ident if y t he examiner's limb as t heir ow n.
Pat ient s w it h spat ial neglect may be able t o det ect cont ralesional visual st imuli
and may not even have ext inct ion but may f ail t o act on cont ralesional st imuli
present ed in space. They may f ail t o act in t he lef t hemispace (egocentri c
hemi spati al negl ect) or may f ail t o act on t he lef t side of t he st imulus
(al l ocentri c spati al negl ect)[ 209] . Spat ial neglect is t est ed by t he line bisect ion
t est , by cancellat ion t asks (t he pat ient is asked t o cross out all lines present ed
randomly on a sheet of paper), or by having t he pat ient copy draw ings. Alt hough
spat ial neglect is most of t en described in t he horizont al plane (lef t spat ial
neglect ), vert ical (alt it udinal) neglect (due t o bilat eral pariet o-occipit al lesions
w it h Balint 's syndrome) and radial neglect have also been described[378, 426] .
Perhaps akin t o allest hesia, involving in t his case audit ory st imuli, is t he
“response-t o-next -pat ient -st imulat ion syndrome” seen w it h right -hemispheric
st roke, in w hich pat ient s responded t o st imuli direct ed at ot her pat ient s as if t he
st imuli w ere direct ed at t hem[50] .
Lesions causing hemispat ial neglect are similar t o t hose causing inat t ent ion and
ext inct ion. Lesions of t he right inf erior pariet al lobule are especially apt t o cause
t his syndrome. The severit y of neglect is increased w it h bot h t he size of t he
lesion and t he degree of prior diff use cort ical damage[283] . Sensory ext inct ion
and hemispat ial neglect may also occur w it h lesions of t he insula [293] , st riat um
and int ernal capsule[204] , or w it h lesions aff ect ing t he caudat e nucleus,
lent icular nuclei, and surrounding w hit e mat t er t ract s (i. e. , lesions t hat disrupt
t he cort ico-st riat o-nigral-collicular pat hw ay) [283, 398, 464] .
These disorders appear more readily and prof oundly w it h lesions of t he right
hemisphere, w hich is nondominant f or language. Elect rophysiologic st udies have
indicat ed t hat t he nondominant hemisphere mediat es at t ent ional mechanisms
direct ed t o bot h hemif ields, w hereas t he lef t hemisphere is mainly concerned
w it h t he right hemispace [253] . This hypot hesis has been f urt her support ed by
clinical st udies t hat have demonst rat ed t hat pat ient s w it h right brain pat hology
are more likely t o make ipsilat eral at t ent ional errors t han pat ient s w it h lef t brain
lesions[ 486] , alt hough lef t -sided ext inct ion has rarely been report ed af t er lef t -
hemisphere lesions[411] . Bilat eral dichot ic audit ory st imulat ion in
commissurot omized pat ient s evidences ext inct ion of st imuli in t he lef t ear
only[ 331] . Pat ient s w it h neglect f rom right -hemisphere lesions are not only
inat t ent ive t o t heir bodies but are also dist ract ed by ext racorporeal st imuli,
especially on t he right [299] . Theref ore, t he right side of t he brain is dominant f or
dist ribut ing at t ent ion across t he ext rapersonal w orld [209, 324, 486] .
Hemiakinesia
Hemiakinesia (i ntenti onal negl ect) is t he expression of unilat eral mot or neglect ,
charact erized by a disinclinat ion t o direct orient ing and explorat ory behaviors
w it h t he head, eyes, and limbs int o t he neglect ed hemispace[52, 325] . The
pat ient may not look t ow ard one side of t he space, alt hough he or she readily
react s t o sensory st imuli coming f rom t hat space, or may not move t he limbs
cont ralat eral t o t he lesion unless specif ically asked t o do so, t hen show ing good
st rengt h. Alt hough sensory neglect result s f rom right -hemispheric lesions and
generally involves predominant ly t he lef t hemispace, hemiakinesia may result
f rom lesions of eit her hemisphere, part icularly t hose aff ect ing t he dorsal, goal-
direct ed, at t ent ional net w ork[86] . Akinesia aff ect s movement s t ow ard t he
cont ralat eral hemispace. Rare cases of at t ent ional errors t o t he ipsilesional
space are more likely w it h basal ganglia or f ront al lesions t han w it h ret ro-
Rolandic lesions[248] . How ever, as at t ent ion and int ent ion are closely linked,
lesions in many of t he areas t hat induce inat t ent ion and ext inct ion may also
cause akinesia. For example, lesions in areas 6 and 8 of t he medial and lat eral
“premot or area” of t he f ront al lobe may cause t his syndrome, w hich is more
common and pronounced w it h lesions of t he right hemisphere[99, 158] . The
dorsolat eral f ront al lobe has reciprocal connect ions w it h unimodal and polymodal
sensory associat ion cort ices and is an area of sensory convergence. Lack of
mult imodal sensory f eedback may explain rare cases of hemiakinesia w it hout
sensory neglect f rom pariet al lesions[457] . As discussed in Chapt er 18, t halamic
lesions aff ect ing t he nonspecif ic int ralaminar nuclei (w hich project t o t he f ront al
lobe) may also cause mot or neglect or akinesia[482] . Akinesia may result f rom
lesions of t he basal ganglia and vent ral t halamic lesions. The basal ganglia
project t o t he vent ral t halamus, and t his “mot or” port ion of t he t halamus also
receives connect ions f rom t he nucleus ret icularis t halami[209] . Theref ore,
degenerat ive or ot her diseases of t he basal ganglia, t halamus, limbic syst em,
and f ront al lobes may cause akinesia[209] .
Nonspatial Inattention
I nat t ent ion may aff ect nonspat ial behavior, such as t he inabilit y t o concent rat e on
a t ask, w it h consequent mot or and verbal i mpersi stence. For inst ance, on
inst ruct ion t he pat ient cannot keep t he arms up and eyes closed f or more t han a
f ew seconds. Failure t o keep t he eyelids closed is a common manif est at ion of
mot or impersist ence [121] . Pat ient s w it h right -sided hemispheric lesions are
more likely t o have mot or impersist ence t han t hose w it h lef t -sided lesions, and
right cent ral and f ront al lesions are more commonly responsible t han more
post erior lesions[245] . Simult aneously, pat ient s are more dist ract ible, at t ending
t o all kinds of irrelevant st imuli and of t en ret urning inappropriat ely t o a previous
mot or or verbal perf ormance (perseverati on). Alt hough dist ract ibilit y t o ext ernal
st imuli is more of t en seen w it h right -sided lesions, lef t f ront al or caudat e lesions
predominant ly impair t he abilit y t o divide at t ent ion bet w een t w o sources
(det ect ion t asks) and t o f ocus at t ent ion on one source (G o/ No-G o t asks)[ 179] .
I n t he verbal sphere, t hese pat ient s are laconic or even mut e and may t end t o
repeat sent ences spoken t o t hem or near t hem (echol al i a) and even t o imit at e
gest ures (echopraxi a). Such dist urbances are most of t en seen in pat ient s w it h
advanced Alzheimer's disease, w ho have diff use cort ical damage, or w it h
met abolic encephalopat hies, w hich in addit ion impair t he subcort ical alert ing
mechanisms. When a f ocal cort ical lesion is responsible, it usually aff ect s t he
mesial aspect of bot h f ront al lobes. Large lesions in t his locat ion cause akinet ic
mut ism: a st at e of mot ionlessness and speechlessness w it h regular sleep–w ake
cycles. Medial diencephalo-mesencephalic lesions can also cause t his syndrome.
Behavioral changes, including short at t ent ion span, apat hy, disinhibit ion, and
aff ect ive dist urbances, may occur w it h unilat eral or bilat eral caudat e lesions,
implying caudat e modulat ion of pref ront al behaviors[40, 320] . I nert ia and loss of
drive, w it h preservat ion of int ellect ual f unct ion, of t en associat ed w it h
st ereot yped act ivit ies w it h compulsive and obsessive behavior, have been
described w it h bilat eral basal ganglia lesions conf ined t o t he lent if orm nuclei,
part icularly aff ect ing t he pallidum [40, 266, 447] .
Perseverat ive behavior has been divided int o t hree cat egories, each w it h it s ow n
anat omic correlat e[402] :
1. Recurrent perseverat ion is a repet it ion of a previous response t o a

subsequent st imulus and is seen w it h lesions of t he lef t hemisphere,
especially in t emporopariet al cort ex.
2. St uck-in-set perseverat ion is an inappropriat e maint enance of a cat egory of
act ivit y and is seen w it h f ront osubcort ical and mesolimbic lesions.
3. Cont inuous perseverat ion is an abnormal prolongat ion of a current act ivit y
and is seen w it h right -hemisphere damage.
I nat t ent ion in t he dement ing processes is also manif est ed in t he f orm of
abnormal verbal ut t erances know n as i ntrusi ons[ 166] . An int rusion is t he
inappropriat e recurrence of a response (or t ype of response) f rom a preceding
t est it em, t est , or procedure. Cholinergic def iciency plays a role in t he genesis
of int rusions in Alzheimer's disease[166] . I n t his disorder, int rusions during f ree
recall correlat e w it h impaired act ivat ion of t he right superior pref ront al cort ex,
w hereas int rusions during cued recall seem t o relat e t o impaired lef t ant erior
medial t emporal act ivat ion[122] . Verbal int rusions have also been described w it h
delirium [476] .
Mot or int rusions have been described in Parkinson's disease[131] .
Emotional Disturbances
The hypot halamus, periaqueduct al gray, and several pont ine and midbrain nuclei
mediat e some of t he most primit ive emot ional responses, mat ching t he ongoing
met abolic variables w it h t he paramet ers set f or t he individual species[102] .
When a deviat ion occurs, or w hen t he circumst ances are ripe f or an act ion t hat
w ould f avor t he survival of t he individual or t he species, a preset behavioral
response occurs in low er animals. Such relat ively simple behavioral responses
are modif ied in humans by phylogenet ically new er st ruct ures, such as t he
neocort ex[ 27] . Some cort ical regions are involved in t he recording and ret rieval
of st imuli t hat prove t o be noxious t o t he individual (limbic cort ex). O t hers allow
t he individual t o communicat e w it h ot her human beings semant ically (language
areas of t he dominant hemisphere) or t hrough f acial expressions and ot her f orms
of “body language” (nondominant hemisphere). St ill ot hers mediat e t he complex
balance of emot ional responses needed f or t he survival and development of a
social communit y (f ront al lobes, t emporal lobes). Finally, t he out w ard expression
of emot ion uses t he mot or syst em.
Theref ore, emot ions and t heir expression depend on t he f ollow ing f act ors:
1. The st at e of arousal of t he individual (alert ness) mediat ed by t he ret icular

act ivat ing syst em, including some t halamic st ruct ures, and t he medial f ront al
cort ex.
2. Veget at ive f unct ions, mediat ed in part by periaqueduct al gray and ot her
brainst em regions, by t he hypot halamus and by limbic st ruct ures [102] ; as
w ell as rew ard mechanisms mediat ed by a complex net w ork, including
dopaminergic syst ems and t he st riat um[119] .
3. A previous-experience ret rieval syst em (memory) mediat ed by t he
hippocampus and ot her port ions of t he limbic syst em.
4. The abilit y t o perceive t he aff ect ive component of various st imuli, such as a
f riendly f ace or a t hreat ening ut t erance. Brain st ruct ures mediat ing t his
f unct ion are relat ed t o t he sensory modalit y involved and t o t he t ype of
emot ional cont ent . The amygdala plays an import ant role in visual st imuli, as
w ell as f or t he t hreat ening qualit y of ot her st imuli, such as audit ory
st imuli[ 186, 474] . The mechanisms by w hich t he amygdala plays t his role
may not be “sensory” in t he usual sense of t he w ord. A pat ient w it h bilat eral
amygdalar damage recognized t he expression of f ear in f aces w hen direct ed
t o look at t he eyes, t he f acial f eat ure t hat best indicat es t his emot ional
st at e[ 2] . The vent ral ant erior port ion of t he insula is specif ically act ivat ed by
f aces show ing disgust , not necessarily as a “sensory” area but perhaps as a
“mirror” area[259] . Regarding language, aphasic pat ient s w it h lesions in t he
lef t inf erior pariet al lobule and superior t emporal gyrus, f or example, are
unimpressed w hen t old “I w ill kill you” in a mat t er-of -f act t one but react t o a
t hreat ening pit ch of voice or an angry f ace[193] . I n cont rast , right
pariet ot emporal–damaged individuals underst and t he semant ic meaning of a
verbal t hreat , but t heir percept ion of t he emot ional overt ones t hat
accompany t he ut t erance is impaired (sensory aprosodi a)[ 176, 391] . Right
pariet o-occipit al lesions lessen t he abilit y t o perceive f acial expression[116] .
I nt erpret ing f acial expression f ails t o act ivat e right f ront o-pariet o-occipit al
and orbit of ront al cort ex in people w it h alexit hymia, a personal t rait
charact erized by a reduced abilit y t o ident if y and describe one's ow n
f eelings[ 239] .
5. The abilit y t o properly evaluat e t he import ance of int ernal and ext ernal
st imuli f or t he survival and w ell-being of t he subject [66, 87, 222] . For
pat ient s w it h bilat eral orbit of ront al dest ruct ive lesions, most social nuances
are t rivial; how ever, t hey may go int o a rage w hen some basic inst inct ive
drives are not sat isf ied. By cont rast , f or pat ient s w it h t emporal lobe epilepsy
even t rivia become t ranscendent al issues. Pat ient s w it h small bilat eral
ant erior cingulat e (area 24) lesions may be unconcerned in t he presence of
painf ul st imuli[82, 470] . Diff erent t ypes of emot ional st at es map t o quit e
specif ic subregions of t he cingulat e gyrus, as show n in Figure 20-8. Pat ient s
w it h bilat eral ant erior t emporal lesions have a bland aff ect . Lesions of t he
sept al region cause enhanced irrit abilit y and rage react ions. Right
orbit of ront al penet rat ing w ounds may cause “edginess, ” anxiet y, and
depression, w hereas lef t dorsof ront al penet rat ing w ounds cause anger and
host ilit y[ 192] . Pat ient s w it h epilept ogenic f oci in t he lef t t emporal lobe t end
t o be paranoid and have ant isocial behavior, w hereas t hose w it h right
t emporal f oci show emot ional ext remes (elat ion, sadness) and denial[428] .
Some pat ient s w it h acut e medial t emporo-occipit al (i. e. , t he
parahippocampal, lingual, and f usif orm gyri) lesions become not only
disorient ed but also agit at ed and abusive (syndrome of agi tated
del i ri um)[ 319] . An acut e conf usional st at e and agit at ed delirium may also
occur w it h lesions of t he brainst em or t halamic ret icular act ivat ing syst em,
w it h lesions of t he medial f ront al lobe, and w it h right middle cerebral art ery
inf arct ion[ 335] .
6. The abilit y t o express emot ion, w hich requires more t han a grossly int act
mot or syst em. Right f ront al hemispheric lesions may cause impairment of t he
volunt ary emot ional int onat ion of speech (motor aprosodi a)[ 391] . Lack of
volunt ary cont rol of t he emot ional expression may adopt anot her f orm,
namely, accent uat ed emot ional expression, t o t he point of irrepressible
laughing or crying unaccompanied by t he corresponding inner f eeling.
Pat hologic laughing or crying result s f rom bilat eral int ernal capsular lesions
t hat also involve t he basal ganglia; f rom lesions in t he subst ant ia nigra,
cerebral peduncles, and hypot halamus; and f rom pronounced involvement of
t he cort icobulbar f ibers, such as occurs in severe suprabulbar amyot rophic
lat eral sclerosis[371] . Pat hologic laughing requires a higher level of
int egrat ion t han pat hologic crying. Pat hologic laughing may rarely herald an
acut e basal ganglia lesion, brainst em st roke, or lef t carot id inf arct ion (f ou
ri re prodromi que)[ 475] .
I t has been post ulat ed t hat lesions t hat mainly aff ect t he lef t hemisphere
t end t o induce pat hologic crying, w hereas laught er appears more of t en af t er
right -hemispheric damage[396] . Likew ise, pat ient s w it h lef t -hemispheric
damage t end t o show depression more of t en t han t hose w it h right -
hemispheric damage[386] . The severit y of depression w as direct ly correlat ed
w it h t he closeness of t he lesion t o t he f ront al pole. Pat ient s w it h lef t brain
damage are of t en anxious, t earf ul, negat ive, and abusive, w hereas pat ient s
w it h right -hemispheric damage are indiff erent and jocular, f urt her suggest ing
t hat t he dominant hemisphere subserves posit ive f eelings and t he
nondominant hemisphere subserves negat ive ones[228] . I n pat ient s w it h a
single st roke, t hose w it h a lef t ant erior cort ical or subcort ical lesion have a
great er f requency and severit y of depression t han pat ient s w it h any ot her
lesion locat ion[441] . Pat ient s w it h right -hemispheric single st rokes do not
show depression but have a signif icant ly higher incidence of undue
cheerf ulness[ 441] . A large subset of pat ient s w it h right -hemispheric damage
are somew hat unaw are of t heir def icit , and such a denial may prevent t he
negat ive eff ect t hat t he handicap might ot herw ise have on t heir mood.
O t her aut hors have f ound no evidence t hat lef t -sided lesions w ere
associat ed w it h more severe or persist ent depressive sympt oms or t hat
right -sided lesions w ere associat ed w it h hypomania[223] . I n several st udies,
major depression w as not specif ically associat ed w it h lesions locat ed
ant eriorly in t he lef t hemisphere[169, 223] .
7. An int act “baseline” aff ect ive sit uat ion (mood), w hich is dist urbed in
endogenous depression and mania. The anat omic subst rat e of t hese
syndromes has not been f ully elucidat ed, but a f ew anat omic sit es seem t o
part icipat e in mood cont rol. St imulat ion or disrupt ion of circuit ry near t he
subt halamic nucleus has result ed in t ransient depression or mania [29, 389,
442] . Correct ion of hyperact ivit y in t he subgenual cingulat e region
(Brodmann's area 25) result ed in t he improvement of severe
depression[ 306] .
FI G URE 20-8 Cingulat e emot ion processing. Depict ed on t he medial aspect

of t he brain is a summary of st udies show ing peak act ivat ion sit es during
t hree simple emot ions. Not e t hat t hey occur in t he cingulat e gyrus w it h rat her
specif ic t opography. (Court esy of Dr. Marí a A. Past or, w it h inf ormat ion f rom
Vogt BA[470] . )
The temporal l obe cont ains limbic st ruct ures t hat are involved in t he modulat ion
of emot ional behavior[458] . Pat ient s w ho survive herpes simplex encephalit is
of t en have memory
dist urbances (see subsequent t ext ) associat ed w it h hypermet amorphosis

(marked t endency t o t ake not ice and at t end t o every visual st imulus), a t endency
t o explore object s orally, agnosias, eat ing and drinking problems, inappropriat e
sexual displays, irrit abilit y, easy dist ract ibilit y, aggressive out burst s, emot ional
blunt ing, periods of apat hy and depression, and episodes of rest lessness and
overact ivit y[ 458] . Pat ient s w it h complex part ial seizures of t emporal lobe origin
may demonst rat e an int erict al behavioral syndrome charact erized by alt ered
sexual behavior (usually hyposexualit y), hypergraphia, and hyper-religiosit y
(e. g. , sudden religious conversions, at t achment t o unort hodox religious groups,
compulsive Bible reading)[ 485] . These pat ient s may also demonst rat e aggressive
behavior, met iculous at t ent ion t o det ail, and circumst ant ialit y of speech w it h
prolonged and det ailed explanat ions of even t he most t rivial event s[485] .
Memory Disturbances
Memory mechanisms diff er depending on t he t ype of inf ormat ion being st ored in
t he brain. To summarize, amygdalohippocampal areas of t he medial t emporal
region and ot her port ions of Papez circuit are import ant f or ret aining event s in
t he lif e of t he individual or dat abase t ype of inf ormat ion, such as t he names of
f amous people. This kind of memory, called epi sodi c memory, is w hat t he
clinician usually calls “memory. ” This sect ion deals most ly w it h episodic memory
and t he localizat ion of it s dist urbances. Procedural memory or skill-based
learning (e. g. , how t o use a t ool) is mediat ed by t he pref ront al cort ex and t he
basal ganglia [182, 372] . Ext ensive lesions of t he brain may impair bot h kinds of
memory and result in t he clinical syndrome of dement ia, described lat er in t his
chapt er. Here w e w ill describe t he localizat ion of t he more rest rict ed amnest ic
syndrome f or episodic memories.
The cort ical amnest ic syndrome or st at e is charact erized by several
f eat ures[ 438] :
1. A mult imodal impairment . Memory is aff ect ed regardless of t he sensory

modalit y in w hich inf ormat ion is present ed.
2. Relat ive preservat ion of at t ent ion, concent rat ion, visuospat ial skills,
language, mot ivat ion, complex percept ual abilit ies, and general int ellect ual
abilit ies.
3. Preserved abilit y t o ret ain inf ormat ion f or short periods (immediat e memory).
I mmediat e memory is disrupt ed, not w it h medial t emporal lesions t hat cause
t he t ypical amnest ic syndrome, but by f ocal cort ical lesions in t he same
areas t hat process a part icular t ype of inf ormat ion [358] . For inst ance,
dominant perisylvian cort ex lesions impair immediat e memory f or verbal
mat erial, lesions in bot h lingual gyri impair immediat e memory f or f aces
(prosopagnosia), and lesions of t he somat osensory area impair immediat e
t act ile memory[202] .
4. I mpaired regist rat ion of new inf ormat ion, know n as anterograde amnesi a.
Episodic memory is impaired but skill-based or procedural learning is
generally unaff ect ed[25, 75] .
5. Variable def icit s in t he recall of memories acquired w it hin a cert ain int erval
bef ore t he onset of t he amnest ic st at e (retrograde amnesi a). Wit h large
bilat eral lesions, t here is a severe memory loss f or w hat happened several
years bef ore t he event . As t he memories relat e t o older mat erial, t hey are
gradually bet t er, so t hat t he pat ient remembers as any normal individual
event s t hat occurred more t han 11 t o 30 years bef ore t he event . How f ar
back t he memories are lost depends on t he degree of mesial t emporal
damage, on w het her t here is addit ional f ront al or t emporal damage, and on
t he t ype of memories. Single event s are not remembered as w ell as
aut obiographical event s and t hese may not be remembered as w ell as
semant ic inf ormat ion. Spat ial inf ormat ion t ends t o be remembered
part icularly w ell. Addit ional lesions of t he f ront al or t emporal lobes may
render t he pat ient unable t o access even remot e memories [26] .
Amnest ic syndromes represent a def icit in consol i dati on, t he set of processes
w hereby inf ormat ion held in t emporary, t ransient f orm is convert ed t o more
permanent st orage. Amnest ic pat ient s maint ain t he abilit y t o place inf ormat ion in
t emporary st ores. The consolidat ion def icit account s f or ret rograde amnesia t hat
ext ends back no more t han 1 t o 2 years. I t is assumed t hat consolidat ive
processes normally cont inue t o f ix memories int o permanent f orm over t his
period. More ext ensive ret rograde amnesia probably represent s a block in t he
ret rieval of exist ing memories.
The amnest ic syndrome is usually due t o processes t hat damage t he medial
t emporal lobes, especially t he amygdala and hippocampus; t he ant erior and
dorsomedial nuclei of t he t halamus; or t he connect ions of t hese st ruct ures [154,
189, 201] . They are part of t he circuit s t hat det ermine w hich memories w arrant
saving and w hich do not and are t heref ore involved in t he regulat ion of t he
consolidat ive process[154] . According t o t he current most w idely accept ed view,
t he hippocampus
init ially w orks along w it h t he neocort ex t o allow memory t o be encoded and t hen
t o be accessible. Subsequent react ivat ion of t he hippocampal net w ork reinst at es
act ivit y in diff erent neocort ical net w orks. This coordinat ed replay across
hippocampal–neocort ical net w orks leads t o a gradual st rengt hening of
neocort ical-neocort ical connect ions, unt il t he neocort ical memory can be
accessed independent of t he hippocampus and be int egrat ed w it h preexist ing
neocort ical memories[154, 438] . Theref ore, remot e memories seem t o be
“st ored” in dist ribut ed cort ical net w orks, part icularly associat ed w it h t he
modalit ies—visual, audit ory, t act ile—involved in t he memory t race.
O rbit of ront al, medial pref ront al cort ex, including t he ant erior cingulat e, and t he
lat eral pref ront al cort ex play a major role bot h in assigning relevance f or st orage
and in ret rieving remot e memories [125, 154, 159] . Many pat ient s w it h memory
loss do not have t he t ypical amnesic syndrome, but have t he at t ent ional
diff icult ies charact erist ic of f ront al dysf unct ion. The human f ront al cort ex helps
mediat e w orking memory, a syst em t hat is used f or t emporary st orage and
manipulat ion of inf ormat ion and t hat is involved in many higher cognit ive
f unct ions[ 358] . Working memory includes t w o component s: short -t erm st orage
(on t he order of seconds) and execut ive processes t hat operat e on t he cont ent s
of st orage. St udies of st orage indicat e t hat diff erent f ront al regions are
act ivat ed f or diff erent kinds of inf ormat ion: st orage f or verbal mat erials act ivat es
Broca's area and lef t -hemisphere supplement ary and premot or areas, st orage of
spat ial inf ormat ion act ivat es t he right -hemisphere premot or cort ex, and st orage
of object inf ormat ion act ivat es ot her areas of t he pref ront al cort ex. Tw o of t he
f undament al execut ive processes are select ive at t ent ion and t ask management .
Bot h processes act ivat e t he ant erior cingulat e and dorsolat eral pref ront al
cort ex[ 431] .
The amygdala plays a role in t he f acilit at ion of remembering emot ionally charged
episodes, or at least remembering t hem as emot ionally charged [126, 423] . I t
seems part icularly import ant f or t he ret ent ion of event s w it h a f earf ul emot ional
connot at ion[ 136, 297] .
The medial t emporal cort ex is heavily connect ed w it h ot her cort ical areas. The
perirhinal cort ex receives st rong project ions f rom unimodal visual areas. The
parahippocampal cort ex receives prominent project ions f rom dorsal st ream
areas, including t he ret rosplenial cort ex, area 7a of t he post erior pariet al cort ex,
and area 46 of t he pref ront al middle t emporal gyrus. Correspondingly, visual
memory is more dependent on t he perirhinal cort ex t han on t he parahippocampal
cort ex, w hereas spat ial memory is more dependent on t he parahippocampal
cort ex, part icularly on t he right side. The parahippocampal cort ex project s t o t he
hippocampus.
Alt hough t here is much t o be learned about how t he f unct ion of t hese st ruct ures
t ranslat es int o memory st orage, it is clear t hat medial t emporal st ruct ures can
signal t he degree of novelt y or f amiliarit y of an event [183] . A remarkable subset
of medial t emporal neurons are select ively act ivat ed by st rikingly diff erent
pict ures of given individuals, landmarks, or object s and in some cases even by
let t er st rings w it h t heir names[377] . Consist ent “recognit ion” occurs alt hough t he
individuals, landmarks, or object s are present ed in various sizes, posit ions, and
view ing angles.
Recognit ion memory is w idely view ed as consist ing of t w o component s, a
recollect ive (episodic) component and a f amiliarit y component . Recollect ion
provides inf ormat ion about t he episode in w hich an it em w as encount ered, and
f amiliarit y provides inf ormat ion t hat an it em w as encount ered but does not
provide any know ledge about t he learning cont ext . I t has been proposed t hat
recollect ion depends especially on t he hippocampus and t hat f amiliarit y depends
more on t he adjacent cort ex, alt hough available dat a in humans st ill do not
complet ely validat e t his not ion[438] .
As bot h medial t emporal and t halamic lesions may cause amnesia, it w ould be
helpf ul f or clinical localizat ion t o know w het her t here are any f eat ures t hat
diff erent iat e t he t w o sit es. This may be a f ut ile endeavor, because t halamic
lesions seem t o cause amnesia, at least in part , by causing a f ailure of
act ivat ion of medial t emporal st ruct ures[74] . How ever, some of t he
sympt omat ology of lesions in eit her sit e may diff er, in part due t o damage of
neighboring st ruct ures or t o f ibers of passage. O ne of t he diff erent ial f eat ures
may be t he t endency t o conf abulat e, t hat is, f or t he pat ient t o creat e f act it ious
responses t o “f ill-in” memory gaps. Pat ient s w it h cort ical amnesia, f rom bilat eral
medial t emporal lesions, t end t o conf abulat e less and t o be more aw are of t heir
def icit t han pat ient s w it h Korsakoff 's psychosis, f rom ant eromedial t halamic
damage. Conf abulat ion w it h t halamic lesions may result f rom impaired act ivat ion
of orbit of ront al and medial pref ront al st ruct ures, of t en hypoact ive af t er acut e
ant eromedial t halamic damage[33, 410] . Anot her diff erence is t hat , alt hough
diencephalic damage causes abnormal st orage and ret rieval but does not
increase t he rat e of f orget t ing, cort ical lesions do[437] .
Lesions of t he lef t t emporal lobe mainly impair t he st orage of language-relat ed
inf ormat ion, w hereas t hose on t he right side aff ect t he st orage
of nonverbal pat t erned mat erials, such as a geomet ric or t onal pat t ern[64] . The
clinical present at ion of t he eff ect of lesions in t hese regions varies according t o
w hich modalit y is aff ect ed and how severely. Acut ely, bot h verbal and nonverbal
memories seem equally aff ect ed, even w it h unilat eral lesions, but , w it h t ime,
lesions of t he lef t hemisphere t end t o aff ect verbal learning more t han visual
learning (t he opposit e occurs w it h right -hemispheric lesions). Because verbal
t asks are most of t en used t o t est memory, such hemispheric “specializat ion” may
explain w hy memory def icit s have been report ed af t er unilat eral lesions of t he
lef t t emporal lobe but not af t er lesions of t he right t emporal lobe.
FI G URE 20-9 The limbic st ruct ures and some of t heir connect ions (according
t o Penf ield and Jasper[362] ) are highlight ed in t he medial view of t he right
hemisphere A = anteri or thal ami c nucl eus; AMYG = amygdal a; G = gyrus; H
= habenul a; MD = medi odorsal t halamic nucleus; MM = mammi l l ary body;
Paraolf . area = paraol f actory area.
Bilat eral cingulat e gyrus lesions and unilat eral f orebrain lesions[401] may also
impair memory, as may bilat eral f ornix damage[167] . Memory loss caused by
hypot halamic or t halamic lesions is discussed in Chapt ers 17 and 18
respect ively. Theref ore, lesions, usually bilat eral, of any of t he st ruct ures of
Papez ci rcui t (hippocampus, f ornix, mammillary body, mammillot halamic t ract ,
ant erior and dorsomedial t halamic nuclei, cingulat e gyrus, and cingulum) (Fig.
20-9) have been report ed t o cause amnesia[191, 325] . The basal f orebrain,
including t he sept al nuclei and nucleus basalis of Meynert , is also an import ant
component of t he limbic net w ork f or memory[325] . The ret rosplenial cort ex
connect s t he ant erior t halamus w it h medial t emporal st ruct ures and may share
f unct ions w it h t he st ruct ures of t he Papez circuit by providing an alt ernat ive
rout e bet w een t he hippocampus and t halamus[463] .
Any disease aff ect ing t he st ruct ures crit ical f or regulat ing memory st orage can
cause t he amnest ic syndrome. Et iologies f or medial t emporal lobe damage
include surgical resect ion, herpes encephalit is, paraneoplast ic encephalit is,
post erior cerebral art ery dist ribut ion ischemia, anoxia, and seizures [78, 219,
240, 499] . The mediodorsal t halamic nucleus and adjacent regions may be
injured by inf arct ion, t umors, and penet rat ing injuries [187, 300] ; w hereas
damage t o t he f ornix may occur w it h t umors, t rauma, inf arct s, and surgery (e. g. ,
removal of a colloid cyst or bilat eral f ornix t ransect ion in pat ient s w it h t emporal
lobe epilepsy) [167, 191, 255] . The basal f orebrain (e. g. , sept al nuclei) may be
damaged by rupt ured ant erior communicat ing art ery aneurysms[118] . The
memory def ect s in Alzheimer's disease are likely relat ed t o pat hology in mult iple
areas, including t he ent orhinal cort ex, pariet o-occipit al regions, and t he f ront al
lobes[ 230] ; t hese pat ient s are much more impaired by t heir memory problems
because of associat ed cognit ive def icit s, such as impaired st rat egy and
planning. Unilat eral amnesic st roke may involve t he t errit ories of t he post erior
cerebral, ant erior choroidal, or t halamic penet rat ing art eries[353] . I n 85% of
pat ient s w it h unilat eral st roke-associat ed amnesia, t he lef t hemisphere is
aff ect ed; lef t amygdalohippocampal or diencephalic dysf unct ion may result in a
part icular vulnerabilit y t o global amnesia[353] .
Smell and Taste
O lf act ory nerve dist urbances are discussed in Chapt er 6. Epilept ogenic lesions
in t he region of t he t emporal uncus may give rise t o hallucinat ions
of smell or t ast e of t en accompanied by mout hing or chew ing movement s.

G ust at ory hallucinat ions may occur as manif est at ions of pariet al, t emporal, or
t emporopariet al seizures and are t hought t o be relat ed t o abnormalit ies of t he
pariet al or Rolandic operculum, or bot h[203] . I n a series of pat ient s w it h
olf act ory hallucinat ions, 8% w ere f ound t o have epilepsy[374] . Ageusi a (lack of
t ast e) may occur af t er bilat eral insular lesions[62] .
Vision
Calcarine cort ex (primary visual area) lesions causing impaired visual acuit y are
discussed in Chapt er 7. This chapt er deals w it h more complex dist urbances t hat
ref lect damage t o t he visual associat ion cort ex or t o ot her regions of t he
cerebral hemispheres involved in t he acquisit ion and processing of visual
inf ormat ion.
Visual Hallucinations and Delusions

Visual hallucinat ions may occur in a number of psychiat ric, medical, neurologic,
and ocular disorders, as w ell as in drug-induced st at es. I n pat ient s w it h ocular
disease, t he hallucinat ions are f ormed, bright , and somet imes complex[220,
429] . Vit reous det achment may cause brief , vert ical f lashes of light (Moore's
light ning st reaks) in t he t emporal visual f ields seen predominant ly w it h eye
movement s[ 494] . The f lashes of light indicat e mechanical st imulat ion of t he
ret ina and are best seen in t he dark or w it h t he eyes closed, w hen t he f lashes
do not compet e w it h ambient light . O pt ic neurit is may be associat ed w it h bright
f lashes of light induced by eye movement (movement phosphenes)[ 109] or in
response t o sudden loud sounds[278] . Pat ient s w it h amaurosis f ugax may
experience colored bright light f lashes or scint illat ions.
Si mpl e vi sual hal l uci nati ons, consist ing of f lashes of light (phot opsias) or lines
of diff erent colors t hat adopt simple pat t erns (zigzag, circle, f ort if icat ion pat t ern)
of t en accompany a def ect ive f ield of vision and indicat e inf eromedial occipit al
disease, usually migraine or an epilept ogenic lesion[278] . The element ary visual
hallucinat ions w it h occipit al epilept ic seizures are predominant ly mult icolored,
w it h circular or spherical pat t erns as opposed t o t he predominant ly black-and-
w hit e zigzag linear pat t erns of migraine[354] . Unf ormed visual hallucinat ions in
one hemif ield (probably ict al in nat ure) seen only w it h vigorous exercise have
been described in pat ient s w it h occipit al brain t umors and may be a specif ic
sympt om of occipit al t umor[279] .
Compl ex vi sual hal l uci nati ons, such as landscapes or animals, are generally
relat ed t o t emporal lobe dysf unct ion[200] . Aut oscopic phenomena (hallucinat ions
of t he self ) and illusory phenomena, such as micropsia and met amorphopsia,
may be seizure manif est at ions. Hippocampal st imulat ion may evoke visual
hallucinat ions. Among st ruct ural lesions, diff use Lew y body disease[200, 336]
and t umors have t he great est t endency t o induce hallucinat ions.
Lesions in t he upper midbrain[172] t hat also involve t he t halamus, of t en
bilat erally, may cause complex visual hallucinat ions t hat have an oneiroid
(dream-like) qualit y (peduncul ar hal l uci nosi s)[ 140] . Peduncular hallucinat ions
are of t en hypnagogic, are usually know n t o be unreal, may be of normal or
lilliput ian proport ions, and may be pleasant t o t he pat ient . I solat ed bilat eral
inf arct s conf ined t o t he medial subst ant ia nigra pars ret iculat a may cause
complex visual hallucinat ions, suggest ing t hat dest ruct ion of t he pars ret iculat a
may be crit ical f or t he development of peduncular hallucinosis[314] . How ever,
peduncular hallucinosis has also occurred f ollow ing lef t cerebral peduncle
inf arct ion[ 117] and right paramedian t halamic inf arct ion w it hout apparent
midbrain involvement [140] . Vivid hallucinat ions of t his t ype preceded a complet e
loss of t he abilit y t o dream (Charcot-Wi l brand syndrome) in a pat ient w it h
bilat eral lesions in t he medial occipit al regions and right lat eral t halamus[43] .
Peduncular hallucinosis has been post ulat ed t o be a release phenomenon relat ed
t o damage t o t he ARAS, t he rost ral project ion of w hich ext ends f rom t he
midbrain t o t he int ralaminar t halamic nuclei[140] .
An et iologically nonspecif ic t ype of complex visual hallucinat ions may occur in t he
elderly w it h impaired vision (Charl es Bonnet syndrome). These recurrent vivid
hallucinat ions occur in t he presence of normal cognit ion and insight and are
usually associat ed w it h severe visual deprivat ion[429] . The hallucinat ions usually
occur in t he evening and are of t en made up of small, bright ly colored people or
object s w it h a cart oon-like appearance. The pat ient is usually aw are of t he
unrealit y of t hese hallucinat ions and may not e t hat t he hallucinat ions change size
or charact er w hen t he subject reaches out t o t ouch t hem. These hallucinat ions
are t hought t o be t he result of a release phenomenon in vent ral t emporo-occipit al
cort ex, an area t hat is poorly act ivat ed by visual st imulat ion in t hese
pat ient s[ 145] . Hallucinat ions of colors, f aces, t ext ures, and object s correlat e
w it h ant icipat ory cerebral act ivit y in t he vent ral ext rast riat e visual cort ex, and
t he cont ent of t he hallucinat ions ref lect s t he f unct ional specializat ions of t he
region. I n a st udy, pat ient s w ho hallucinat ed
in color had act ivat ion of t he f usif orm gyrus in an area corresponding t o t he color
cent er, area V4, w hereas t he pat ient w ho hallucinat ed in black and w hit e, had
act ivat ion out side t his region[145] . A pat ient w ho hallucinat ed an unf amiliar f ace
had addit ional act ivat ion of t he lef t middle f usif orm gyrus, an area t hat responds
t o unf amiliar f ace st imuli. Pat ient s w ho hallucinat ed brickw ork, f ences, or a map
had act ivat ion of t he collat eral sulcus, an area t hat responds t o visual t ext ures. A
pat ient w ho hallucinat ed object s had act ivat ion of t he middle f usif orm gyrus, an
area t hat responds t o visually present ed object s[145] .
O t her posit ive visual phenomena experienced by pat ient s w it h part ial visual loss
include tessel l opsi a (regular, repeat ing pat t erns), dendropsi a (branching
pat t erns) and hyperchromatopsi a (hyperint ense, brilliant colors)[ 144] .
Simple and complex hallucinat ions may be classif ied pat hogenet ically int o t hree
groups: (a) t hose due t o increased irrit abilit y of t he cerebral cort ex (“ict al”),
w hich are t ypically st ereot yped and more likely t o be associat ed w it h ot her
seizure manif est at ions; (b) t hose due t o nonepilept ogenic cort ical lesions, such
as diff use Lew y body disease[200] ; and (c) t hose due t o impaired vision,
t ypically w it h visual acuit y of 20/ 50 or less (“release hallucinat ions”), w hich are
less st ereot yped, longer in durat ion or cont inuous, likely t o occur in t he blind
port ion of t he visual f ield, and perceived as unreal by t he pat ient [277] . They may
range in complexit y f rom simple phosphenes t o w ell-f ormed visions, such as
people, vehicles, or f urnit ure. Release hallucinat ions are t hought t o represent t he
liberat ion of endogenous cerebral visual act ivit y f rom “cont rol” by higher visual
inhibit ory cent ers and may result f rom lesions anyw here in t he visual pat hw ays
(ret ina t o occipit al cort ex), regardless of t he complexit y of t he hallucinat ion[152,
277] . For inst ance, a pat ient w it h bilat eral occipit al inf arct s and pure alexia had
nonet heless visual hallucinat ions in t he f orm of grammat ically correct , meaningf ul
w rit t en sent ences or phrases, of t en in t he second person and w it h a t hreat ening
and command-like nat ure[146] .
I rrit at ive lesions are, on t he ot her hand, more numerous w it h disease of t he
nondominant hemisphere and more complex w it h t emporal lobe lesions[277] .
O t her common causes of visual hallucinat ions include narcolepsy (hypnagogic or
hypnopompic hallucinat ions), drugs, and psychiat ric disorders[312] .
O ther vi sual i l l usory phenomena include polyopia (seeing a single t arget as
mult iple), cerebral macropsia, micropsia, or met amorphopsia, palinopsia
(persist ence or recurrence of t he visual image once t he object has been
removed), and visual allest hesia (t ransposit ion of an object seen in a visual f ield
t o t he cont ralat eral visual f ield). Unlike binocular diplopia, cerebral polyopia
occurs w it h monocular view ing, bot h images are perceived w it h equal clarit y,
does not resolve w it h a pinhole, and is unchanged w it h view ing monocularly w it h
eit her eye or binocularly. Most inst ances of cerebral polyopia involve only double
vision and are due t o occipit al or pariet o-occipit al lesions. How ever, t he
subject ive experience of mult iple copies of t he same image in a grid-like pat t ern
(ent omopia or “insect eye”) has been described w it h migraine[288] .
Wit h pal i nopsi a, t he image recurs immediat ely af t er divert ing t he gaze or w hen
t he st imulus object is w it hdraw n. The image is f requent ly achromat ic, may be
revived by blinking, is not aff ect ed by eye closure, and moves in t he direct ion of
t he eye movement s (rarely, opposit e t o eye movement s). These illusory
phenomena occur on t he same side as an impaired but not blind visual f ield and
are associat ed w it h occipit ot emporal disease, of t en epilept ogenic[234, 492] .
Also, palinopsia may occur during recovery f rom cort ical blindness in t he
recovering port ion of t he visual f ield. Most cases of palinopsia occur w it h f ocal,
nondominant pariet o-occipit al[ 30] or occipit ot emporal[318] lesions, alt hough
rarely post erior lef t hemisphere[30, 329] or more ant eriorly placed pat hology[30,
236] may cause t his def ect . Specif ic causes of palinopsia include t umor [30] ,
ischemia[ 318] , t rauma, art eriovenous malf ormat ion, abscess[13, 360] , migraine,
carbon monoxide poisoning, drugs (e. g. , mescaline, lysergic acid diet hylamide
[ LSD] , t razodone, 3, 4-met hylenedioxymet hamphet amine [ Ecst asy] , int erleukin 2)
[ 226, 243, 329] , mult iple sclerosis[236] , and cerebral vasculit is[48] . Palinopsia
may also be t he present ing manif est at ion of Creut zf eldt -Jakob disease[376] or
f ollow enucleat ion[177] . O t her t han possibly being due t o seizures[30, 234] ,
palinopsia may also be due t o prolongat ion or pat hologic exaggerat ion of a
normal af t er-image[ 48] , unconscious visual memory[376] , or release
hallucinat ions[ 92] .
Focal seizures arising in t he neocort ex of t he t emporal lobe give rise t o visual
illusions (déjà vu, already seen; jamai s vu, never seen bef ore) or t o experient ial
illusions (déjà veçu, already lived; jamai s veçu, never experienced bef ore). The
pat ient f eels a st rong sense of f amiliarit y w it h scenes or experient ial sit uat ions
t hat in realit y he or she has never seen or experienced bef ore or, on t he
cont rary, a sense of st rangeness about visual st imuli such as t he f ace of a close
relat ive or experient ial sit uat ions t hat should be f amiliar.
Visual Agnosia
Visual agnosia is an impairment of t he abilit y t o recognize object s visually in t he
absence of a loss in visual acuit y or general int ellect ual f unct ions t hat w ould
account f or it [104, 394] . Tw o f act ors are at
w ork in object recognit ion: (a) t he act of conscious percept ion of a sensory
impression (percepti on) and (b) t he act of linking t he cont ent of t he percept ion
w it h previously encoded percept s, t hereby acquiring meaning (associ ati on)[ 381] .
Theref ore, t here may be t w o t ypes of visual agnosia: appercept ive visual
agnosia and associat ive visual agnosia.
1. Appercepti ve vi sual agnosi a. Alt hough t hese pat ient s avoid obst acles w hen
w alking, in many ot her aspect s t hey behave as if t hey w ere blind. They
cannot name it ems present ed t o t hem, draw t hem, or mat ch t hem t o
samples. They cannot point t o object s named by t he examiner. Yet t hey can
dist inguish small changes in t he int ensit y or hue of a minut e source of light ,
and visual acuit y and visual f ields are normal. Their def ect lies in an
impairment of visual pat t ern recognit ion. Some of t hem indicat e t hat st ill
object s are invisible but t hat t hey st and out f rom t he background as soon as
t hey move. Bilat eral lesions, of t en ischemic, of t he calcarine cort ex or
occipit ot emporal regions cause t his dist urbance, w hich t ends t o appear in
t he process of recovery f rom cort ical blindness[433] . The ext rast riat al visual
pat hw ay, w hich includes t he pulvinar, superior colliculus, and pariet al lobe,
may play a role in t he recognit ion of light and movement in t hese
pat ient s[ 51] .
2. Associ ati ve vi sual agnosi a. This t erm ref ers t o t he def icit of pat ient s w ho
cannot recognize object s visually but can draw t hem or point t o t hem w hen
t hey are present ed in an array of object s (i. e. , percept ion is clearly int act )
[ 394] . Theref ore, a visual ident if icat ion disorder is isolat ed f rom a
discriminat ion disorder[369] . Pict ure ident if icat ion is usually more diff icult
t han t he ident if icat ion of real object s. I n t he process of recovery, t his def icit
t ends t o progress int o a milder def icit , opti c aphasi a, w hich is charact erized
by t he inabilit y t o name object s t hat are recognized, as evidenced by t he f act
t hat t heir use can be explained.
These t w o dist urbances are of t en associat ed w it h right homonymous hemianopia,

pure alexia, and color-naming def icit s. They usually occur f ollow ing lesions
aff ect ing t he mesial aspect of t he lef t occipit al lobe and t he splenium of t he
corpus callosum.
Cerebral Ach romatopsia an d Color Agn osia

Pat ient s w it h cort ical col or bl i ndness ( achromatopsi a) cannot read I shihara
plat es or sort colors according t o hue. Acquired achromat opsia appears w it h
bilat eral or nondominant inf erior occipit ot emporal lesions t hat damage t he lingual
and f usif orm gyri (t he calcarine cort ex is spared); t his abnormalit y is usually
associat ed w it h inf racalcarine lesions t hat damage t he middle t hird of t he lingual
gyrus and also w it h inf racalcarine lesions t hat damage t he w hit e mat t er
immediat ely behind t he post erior t ip of t he lat eral vent ricle [54, 98, 106, 384,
420, 496] . Cerebral achromat opsia is most commonly caused by vert ebrobasilar
vascular disease, but may also be not ed w it h herpes simplex encephalit is,
met ast at ic disease, f ollow ing recurrent f ocal seizures, w it h dement ing illnesses,
or as a t ransient phenomenon w it h migraine. Vascular lesions causing
achromat opsia involve t he inf erior occipit al branch of t he post erior cerebral
art ery sparing it s calcarine branch, w hich supplies t he primary visual cort ex.
Color is processed and “ext ract ed” by cerebral st ruct ures diff erent f rom t he
ones t hat handle t he sense of dept h or of spat ial int egrat ion. I n t he human being,
t he color percept ion area, corresponding t o area V4 in t he monkey, varies
bet w een individuals in absolut e t erms but is invariably f ound on t he lat eral
aspect of t he collat eral sulcus on t he f usif orm gyrus[315] . I t mediat es color
percept ion f or bot h t he low er and upper quadrant s of t he respect ive hemif ields,
t he superior visual f ield being represent ed more medially on t he f usif orm gyrus
and t he inf erior f ield more lat erally [106, 224, 315] . Pat ient s w it h achromat opsia
of t en have associat ed superior quadrant anopsia (bilat eral superior alt it udinal
def ect s) because t he inf erior st riat e cort ex or opt ic radiat ions are aff ect ed.
Pat ient s w it h unilat eral occipit ot emporal inf arct s may have inf erior
hemiachromat opsia w it h an accompanying superior quadrant anopsia[361]
Pat ient s w it h col or agnosi a can read I shihara plat es or sort colors according t o
hue but cannot name colors or point t o a color named by t he examiner; how ever,
t hey perf orm w ell in verbal–verbal t asks (e. g. , “t ell me t he color of t he sky”).
Dominant hemispheric lesions t hat involve t he inf eromedial aspect of t he occipit al
and t emporal lobes are most probably responsible f or color agnosia. Pat ient s
w it h color agnosia usually have an associat ed right homonymous hemianopia and
pure alexia (see subsequent t ext ), w it h t he lesion responsible f or t his condit ion
aff ect ing t he lef t mesial subsplenial area, w hich is t ransit ional bet w een t he
occipit al and t emporal lobes. The hemianopia is due t o addit ional involvement of
t he lat eral geniculat e body, opt ic radiat ions, or calcarine cort ex.
Bilat eral inf erior occipit ot emporal lesions also cause t he inabilit y t o ident if y
f aces visually (prosopagnosi a) or object s t hat are visually similar, such as a
specif ic car in a parking lot (Fig. 20-10) [83, 101, 104, 418] . Pat ient s w it h
prosopagnosia may be unable t o recognize even members of t heir f amilies unless
t hey speak, at w hich t ime t heir
voices are recognized. How ever, t hese pat ient s are st ill able t o perceive f aces
and ident if y separat e f acial f eat ures[112] . Pat ient s w it h prosopagnosia may also
have diff icult y in recognizing phot ographs or pict ures of w ell-know n personalit ies
or even f ail t o recognize pict ures of t hemselves[91] . An ext reme example is “t he
phenomenon of t he mirror” in w hich t he pat ient looks at himself or herself in t he
mirror and sees “not hing at all”[91] . I n most post mort em examinat ions of
pat ient s w it h prosopagnosia, bot h f usif orm gyri have been dest royed or
disconnect ed, suggest ing t hat t his st ruct ure f unct ions as a visual associat ion
area f or t he recognit ion of specif ic f aces and t hat t his def icit is likely a part ial
visual memory def icit [83, 101] .
FI G URE 20-10 Medial aspect s of t he post erior port ion of bot h hemispheres.
Prosopagnosia and ot her visual agnosias result f rom t emporo-occipit al
lesions (verti cal hatchi ng), w hereas visual simult anagnosia t ends t o f ollow
bilat eral pariet o-occipit al lesions (sti ppl i ng). Unilat eral lesions of eit her
hemisphere may cause a cont ralat eral f ield def ect and hemiachromat opsia.
Unilat eral lef t occipit ot emporal lesions t hat also involve t he splenium of t he
corpus callosum result in t he syndrome of alexia w it hout agraphia. (Modif ied
f rom Damasio AR, Damasio H, Van Hoesen G W. Prosopagnosia: anat omic
basis and behavioral mechanisms. Neurol ogy 1982; 32: 331–341. )
Some pat ient s w it h prosopagnosia recognize f aces bet t er t han object s, and vice
versa[ 16, 61] . The dissociat ion bet w een f ace and object processing has been
suggest ed by f unct ional neuroimaging st udies of normal individuals[435] .
Cerebral act ivat ion during an object -recognit ion t ask occurred essent ially in t he
lef t occipit ot emporal cort ex and did not involve t he right -hemisphere regions t hat
w ere specif ically act ivat ed during f ace ident if icat ion[347] . An area specif ically
at t uned t o t he recognit ion of f aces is locat ed in t he f usif orm or occipit ot emporal
gyrus, midw ay bet w een it s ant erior and post erior ext ent . Bilat eral in many
individuals, it is only right sided in some[435] . Just lat eral t o it t here is an area
t hat becomes act ivat ed during t he percept ion of body part s[412] . Alt hough
post mort em st udies have revealed bilat eral lesions of t he f usif orm gyri in
pat ient s w it h prosopagnosia, uni l ateral right occipit ot emporal lesions may also
cause prosopagnosia [138, 263, 264, 419] . Prosopagnosia may be associat ed
w it h agnosia f or noncanonical view s (e. g. , t he pat ient is unable t o ident if y a
f olded pair of eyeglasses but is able t o correct ly ident if y t he glasses w hen t hey
are unf olded and present ed in a more convent ional perspect ive) and a st range
“paradoxical know ledge” (e. g. , w hen conf ront ed w it h a pict ure of t he Mona Lisa,
t he pat ient said, “This cannot possibly be Mona Lisa”)[ 264] . Progressive
prosopagnosia may occur in relat ive isolat ion associat ed w it h select ive right
t emporal lobe at rophy as a degenerat ive process, in w hich case it may begin as
a modalit y-specif ic disorder (i. e. , an inabilit y t o recognize f aces) and progress
t o a cross-modalit y loss of person-based semant ic know ledge[138] .
Prosopagnosia usually occurs af t er bilat eral post erior cerebral art ery occlusions
but has also been described w it h head t rauma, encephalit is, hypoxia, t umors,
abscess, hemat oma, Alzheimer's disease, Parkinson's disease, and as a
development al def ect .
Landmark agnosi a. Some pat ient s have diff icult y f inding t heir w ay around
because t heir abilit y t o recognize f amiliar landmarks is impaired[262] . Most of
t hese pat ient s had right t emporo-occipit al lesions. A discret e region in t he dept h
of t he right lingual sulcus, st raddling t he
lingual and parahippocampal gyri is specif ically act ivat ed w hen view ing buildings
and ot her landmarks [3, 435] .
Visu al Simu ltan agn osia

This phenomenon may underlie some of t he agnost ic def icit s described in t he
preceding t ext . The t erm ref ers t o an inabilit y t o appreciat e t he meaning of t he
w hole, t hough t he element al part s are w ell recognized. I f t he pat ient is
present ed w it h several small f igures, he or she sees only one of t he f igures yet
is able t o ident if y all of t he f igures individually if t hey are present ed separat ely.
I f present ed w it h a complex f igure composed of mult iple subunit s (e. g. , t he
“Cookie Thef t Pict ure” f rom t he Bost on Diagnost ic Aphasia Examinat ion), t he
pat ient is unable t o recognize t he w hole f igure. Pat ient s w it h simult anagnosia
may have visual f ield def ect s (e. g. , unilat eral or bilat eral inf erior quadrant ic
def ect s), but f ormal t est ing is diff icult because t he pat ient s f ail t o keep t heir
eyes f ocused on a t arget . Failure of analysis of t he diff erent visual it ems and
int egrat ion int o a w hole is part ially mediat ed by a disrupt ion of t he normal
explorat ory eye movement s t hat allow t he ident if icat ion of an assembly of
object s in space. Simult anagnosia has also been at t ribut ed t o an inabilit y t o
sust ain visuospat ial at t ent ion across an array, corresponding t o processing
f ailure at a level of long-range (global) spat iot emporal int eract ions among
converging input s f rom early vision[383] , or, t o put it anot her w ay, t o an
impairment in t he process by w hich act ivat ed st ruct ural descript ions are linked t o
inf ormat ion coding t he locat ion of object s[89] .
Some pat ient s w it h simult anagnosia may “look but not see, ” w it h apparent
“disappearance” of st at ionary object s f rom direct view [382] . This phenomenon
result s f rom bilat eral superior occipit al lobe lesions and indicat es t hat at t ent ion
mechanisms t hat permit sust ained aw areness of visual t arget s depend on t he
superior visual associat ion cort ices and are relat ively separat e f rom mechanisms
t hat shif t gaze and drive visual search[382] .
Pat ient s w it h visual simult anagnosia of t en have ot her component s of t he so-
called Bal i nt's syndrome, w hich f ollow s bilat eral pariet o-occipit al lesions in t he
convexit y of t he hemispheres and is charact erized by (a) f ailure t o shif t gaze on
command and diff icult y redirect ing at t ent ion volunt arily (apraxia of gaze or
spasm of f ixat ion), (b) opt ic at axia, a dist urbance of reaching a t arget under
visual cont rol, manif est ed by clumsiness of object bound movement s of t he hand
perf ormed under visual guidance [97, 364, 367] , and (c) decreased visual
at t ent ion, aff ect ing mainly t he peripheral visual f ields and result ing in const rict ion
of t he f ields t o “t unnel vision”[205] . Some pat ient s w it h Balint 's syndrome may
demonst rat e alt it udinal neglect (i. e. , ext inguish t he st imulus present ed in t he
low er quadrant s during double simult aneous st imulat ion across t he vert ical
meridian), suggest ing t hat bilat eral pariet al damage can lead t o mult imodal
at t ent ional and explorat ory def icit s along t he vert ical dimensions of
ext rapersonal space[378] . I t should also be not ed t hat opt ic at axia may occur in
a “pure” f orm w it h unilat eral post erior pariet al cort ical lesions[364] .
When all t he element s of t he syndrome are present , t he pat ient has bilat eral
post erior w at ershed lesions in t he convexit y of t he hemispheres [367] or diff use
cort ical processes w it h a post erior pariet al preponderance (e. g. , subacut e
Human I mmunodef iciency Virus [ HI V] encephalit is, Creut zf eldt -Jakob disease,
spongif orm degenerat ion, adrenoleukodyst rophy, progressive mult if ocal
leukoencephalopat hy, or Alzheimer's disease) [20, 409, 453, 462, 468] .
Simult anagnosia may be t he present ing f eat ure or a prominent impairment in
pat ient s w it h Alzheimer's disease, especially w hen cort ical at rophy is
predominant ly post erior (visual variant of Alzheimer's disease)[ 453] . These
pat ient s diff er f rom ot her pat ient s w it h Alzheimer's disease in t hat t hey usually
present t o an opht halmologist rat her t han a neurologist , have relat ively
preserved visual acuit y, do not have color anomia t o conf ront at ion, are relat ively
young at onset , ret ain insight , and keep t heir sense of humor. These pat ient s
have language def icit s, cannot read, have visuospat ial diff icult y, and have
prominent bilat eral occipit opariet al at rophy on imaging st udies.
Alexia
The abilit y t o read can be impaired by lesions in very diff erent areas of t he
cerebral hemispheres. Those t hat cause aphasi a, discussed in t he subsequent
t ext , of t en aff ect t o some ext ent t he abilit y t o underst and w rit t en language
(anteri or al exi a). Ant erior perisylvian lesions t hat cause Broca's aphasia may
part icularly aff ect t he pat ient 's abilit y t o read let t ers (l i teral anomi a, l i teral
al exi a, or l etter bl i ndness) despit e t he preserved abilit y t o read and comprehend
w hole f amiliar w ords[31, 252] . These pat ient s also have diff icult y underst anding
sent ences w hen t he meaning depends on synt ax (e. g. , “He show ed her t he girls'
hat s”). Lef t supramarginal gyrus damage may be crit ical f or such impairment of
synt act ic comprehension[392] . Most pat ient s w it h Wernicke's aphasia f ail t o
underst and bot h spoken and w rit t en language, alt hough t hey may read aloud
quit e f luent ly. Pat ient s w it h lesions rest rict ed t o t he superior t emporal gyrus can
comprehend w rit t en language much bet t er t han spoken language[206] .
Pat ient s w it h impaired saccadic eye movement s and an at t ent ional disorder may
complet e t he
beginning or end of a w ord or sent ence t hey have scanned imperf ect ly by adding
a high-f requency beginning or ending. Theref ore, “Thursday” becomes “t oday” f or
a right -hemisphere–damaged pat ient , and “lat ent ” becomes “lat er” f or a lef t -
hemisphere–damaged pat ient . The pat ient w it h a right -hemispheric lesion may
make omissions (“f lame” becomes “lame”) or addit ions (“act ” becomes “t act ”) as
w ell as subst it ut ions (“t one” becomes “bone”). This disorder is called negl ect
dysl exi a, or attenti onal dysl exi a. More of t en, t hese pat ient s read only t he w ords
t o t he right or t o t he lef t of a print ed paragraph. Such paral exi as (subst it ut ions
in reading) may occur w it h cort ical or diencephalic disease. Paralexic errors
rest rict ed t o t he lef t end of w ords (lef t hemiparalexia) have been described w it h
lesions of t he lef t side of t he splenium of t he corpus callosum; some of t hese
pat ient s had complet e right hemianopias, and t heir lef t -sided reading errors
w ere at t ribut ed t o a ret inot opically rest rict ed disconnect ion pat t ern t hat
select ively disrupt ed t he t ransf er of inf ormat ion originat ing f rom t he peripheral
lef t visual f ield[42] .
At t ent ional dyslexia may also occur as a f orm of simult anagnosia, w hen single
w ords are read normally but several w ords t oget her are incorrect ly read. These
pat ient s may also ident if y single let t ers but not let t ers in w ords. Reading may
show lit eral migrat ion errors in w hich a let t er f rom one w ord is subst it ut ed at t he
same place in an adjacent w ord (“long t urn” becomes “t ong t urn” or “long lurn”).
This impairment occurs w it h lef t t emporo-occipit al junct ion or lef t pariet al
lesions.
Alexia Du e to Parieto-occipital Lesion s

These lesions may or may not be associat ed w it h impaired w rit ing abilit y
(agraphia).
Al exi a Wi thout Agraphi a (Pure Al exi a or Pure Word Bl i ndness). These pat ient s
cannot read but are able t o w rit e on dict at ion[115] . Visual ident if icat ion of
individual let t ers may be possible in some cases. I n cont rast t o t heir marked
diff icult y in ident if ying visual pat t erns, t hese pat ient s may ident if y t he w ord by
t racing t he let t ers (kinest het ic “reading”). They can also read digit s and
mult idigit numbers but of t en have color agnosia. Alexia w it hout agraphia result s
f rom damage t o t he pat hw ays conveying visual input f rom bot h hemispheres t o
t he dominant angular gyrus, w hich it self remains int act but disconnect ed f rom
visual regions; it usually occurs w it h combi ned lesions of t he dominant medial
occipit al region (part icularly lesions involving t he cort ex around and below t he
calcarine f issure) and t he inf erior f ibers of t he splenium of t he corpus callosum
(splenial-occipit al syndrome) (Fig. 20-11) [4, 34, 98, 115, 195] . I t may also
rarely occur w it h inf arct ion of t he lef t lat eral geniculat e body and t he splenium of
t he corpus callosum (spleniogeniculat e variat ion)[ 445] w it h a si ngl e lesion of t he
dominant occipit ot emporal paravent ricular w hit e mat t er behind, beneat h, and
beside t he occipit al horn of t he lat eral vent ricle[98, 195] , or w it h a more superior
and rost ral lesion in t he dominant hemisphere pariet o-occipit al or pariet al w hit e
mat t er (subangul ar or paraventri cul ar al exi a) [ 194, 233, 370] .
Alexia w it hout agraphia is usually associat ed w it h a right homonymous
hemianopia or right hemiachromat opsia but may occur w it hout visual f ield def ect s
w it h dominant pariet o-occipit al[ 194, 233] or t emporo-occipit al lesions[269] . I t
has also been described in a lef t -handed pat ient w it h a right occipit al
lesion[ 368] .
Al exi a wi th Agraphi a (Central Al exi a). I n addit ion t o t he reading and w rit ing
dist urbance, t hese pat ient s usually have acalculia, f inger agnosia, right –lef t
disorient at ion, and diff icult y w it h spelling w ords and underst anding spelled-out
w ords. A pure angular gyrus lesion is most likely if t he pat ient does not have a
Wernicke's aphasia. Pat ient s w it h sensory aphasia of t en have alexia w it h
agraphia, and t heir lesion ext ends t o t he superior t emporal gyrus. Many pat ient s
w it h alexia w it h agraphia have a part ial or complet e G erst mann's syndrome.
Al exi a f or Brai l l e i n Pati ents wi th Earl y Bl i ndness. Support ing t he role f or t he
st riat e region t o support Braille reading in congenit ally and early blind subject s,
a w oman w it h early blindness w as report ed t o lose t he abilit y t o read Braille
af t er a bilat eral occipit al st roke[198] .
Al exi a f or Japanese Kanji. Japanese w rit ing can use morphograms (Kanji ),
imit at ing t he shape of t he object being ment ioned, or phonograms (Kana) similar
t o t he ones used f or alphabet ic languages like English. Alexia f or Kana has
similar localizat ion as alexia f or English. I n cont rast , cerebral act ivat ion w it h
Kanji is more pronounced in t he lat eral f usif orm gyrus (Brodmann area 37) and
lesions in t his area or bilat eral inf erior t emporo-occipit al regions are more likely
t o cause alexia f or Kanji [ 346, 400] .
An ton 's Syn drome (Den ial of Blin dn ess)

Pat ient s w it h acut e, bilat eral, and ext ensive medial occipit al lesions t hat render
t hem blind may deny having any diff icult y w it h seeing (visual anosognosia) and
conf abulat e about w hat t hey “see. ” Such a phenomenon of t en appears in t he
set t ing of a generalized met abolic encephalopat hy. When relat ed t o discret e
lesions, t hese are likely t o ext end t o t he lat eral aspect of t he occipit al lobes and
reach t he pariet al lobes[170] . I t is unclear w het her t halamic involvement in t he
case
of post erior circulat ion inf arct s may be crit ical f or t he genesis of Ant on's
syndrome in some pat ient s. The anosognosic component of cort ical blindness
may be secondary t o right -hemispheric dysf unct ion or t o disrupt ion of t halamic
connect ions t o t he right pariet al associat ion cort ex, alt hough denial of a
hemianopic f ield def ect (hemi anopi c anosognosi a) may happen as of t en w it h
lef t -sided as w it h right -sided lesions[76] . I t has also been suggest ed t hat denial
of blindness may result w hen occipit al cort ex lesions ext end beyond t he
calcarine cort ex t o include visual associat ion cort ices (areas 18 and 19)[ 93] .
Pat ient s w it h Ant on's syndrome of t en conf abulat e about t heir visual def icit as
w ell as event s subserved by recent memory, t hereby suggest ing t hat t hese
pat ient s may also have anosognosia f or t heir memory def icit similar t o
Korsakoff 's syndrome[150] .
FI G URE 20-11 Represent at ion of t he visual pat hw ays in a low horizont al

sect ion of t he brain. Alexia w it h agraphia result s f rom lesions t hat involve t he
lef t angular gyrus (obl i que hatchi ng). Alexia w it hout agraphia occurs w it h
lesions aff ect ing t he lef t medial occipit ot emporal cort ex and t he f ibers t hat
reach t he angular gyrus f rom t he right occipit ot emporal cort ex. These f ibers
are of t en damaged in t he splenium of t he corpus callosum but may also be
dest royed as t hey sw eep lat eral t o t he pariet o-occipit al f issure. (Modif ied
f rom Dejerine J. Sémiologie des aff ect ions du syst ème nerveux. Paris:
Masson, 1926.)
Ant on's syndrome has also been described w it h lesions of t he ant erior aff erent
visual syst em (e. g. , ocular, opt ic nerve, and chiasmal lesions); in most of t hese
cases t here w as associat ed evidence f or superimposed diff use cognit ive
dysf unct ion[ 313] . A pat ient w ho denied monocular complet e visual loss af t er
t raumat ic damage t o t he opt ic nerve had bilat eral f ront al cont usions, w hich w ere
suspect ed t o be responsible f or t he anosognosia[313] .
Disturbances in the Processing of Auditory Information

Auditory Hallucinations
This “posit ive” sympt om has lit t le localizing value because it can occur w it h
lesions anyw here bet w een t he ear and t he t emporal cort ex. Audit ory
hallucinat ions occasionally f ollow impaired hearing, part icularly w hen t here is an
at t ent ional def ect due t o a met abolic brain disease [196, 283, 330] .
Approximat ely 20% of t emporal lobe t umors may be accompanied by audit ory
hallucinat ions, w hich are most common as a sympt om of schizophrenia and
accompany inf requent ly t he alcohol w it hdraw al syndrome. I n pat ient s w it h
organic cerebral disease, unilat eral audit ory hallucinat ions usually indicat e a
lesion in t he cont ralat eral hemisphere[356, 450] . Alt hough some st udies have
emphasized an import ant role of t he nondominant hemisphere in
t he development of audit ory hallucinat ions of t he musical t ype[38] , ot her report s

have suggest ed t hat t he t ype of audit ory hallucinat ion (verbal vs. musical) is not
consist ent ly associat ed w it h a lesion on eit her side[356] . Audit ory hallucinat ions
(including musical hallucinat ions) may also occur w it h vascular lesions of t he
rost ral pont ine t egment um and w it h low er midbrain t umors (t hese pat ient s had
hearing loss and a clear sensorium)[ 69, 339] and have also been described w it h
caudal pont ine hemorrhage[265] and brainst em encephalit is[128] . Verbal
hallucinat ions are common in t he acut e st age of w ord deaf ness (see subsequent
t ext ).
Hearing Loss
Lesions in t he audit ory pat hw ays as f ar as t he cort ex are discussed in Chapt er
11. Unilat eral lesions rest rict ed t o t he primary audit ory cort ex (t he post eromedial
part of t he t ransverse t emporal gyrus of Heschl[286] ) remain asympt omat ic, but
t hey can be det ect ed w it h dichot ic st imulat ion and ot her met hods. Pat ient s w it h
bilat eral lesions of t he audit ory cort ex manif est a spect rum of disorders ranging
f rom cort ical deaf ness t o audit ory agnosia, pure w ord deaf ness or amusia (or
bot h), and milder dist urbances in t he t emporal analysis of sounds. The clinical
present at ion depends on t he degree of involvement of t he primary audit ory
cort ex[ 322] .
A number of pat ient s have been report ed w ho had severe hearing loss af t er
bilat eral t emporal or t emporopariet al lesions [21, 195, 273, 451] or bilat eral
subcort ical lesions[451] . I n most cases, how ever, t he severe hearing loss
event ually resolved w it h only minor residual audiomet ric def icit accompanied by
varying degrees of impairment in t he abilit y t o int erpret nonverbal as w ell as
verbal sounds (w ord deaf ness or audit ory agnosia)[ 451]
Audi tory agnosi a is an impaired capacit y t o recognize sounds despit e adequat e
hearing as measured by st andard audiomet ry[19] and may be verbal, nonverbal,
or generalized. Audit ory agnosia is seen w it h unilat eral[436] or bilat eral[63]
t emporal lobe damage and may also occur w it h bilat eral subcort ical lesions
sparing t he cort ex[337] . Diff erent sounds, such as ringing of t he phone or
clapping of hands, cannot be dist inguished or localized. Some sounds of a
normal int ensit y may be perceived as having an annoying qualit y (dysacusis).
The spoken w ord cannot be ident if ied eit her (pure word deaf ness), alt hough
t hese pat ient s may read and speak quit e normally, if loudly on occasion. Pure
w ord deaf ness result s f rom bilat eral t emporal cort ical lesions[88] or f rom
bilat eral subcort ical lesions t hat isolat e t he primary audit ory cort ex f rom audit ory
input by int errupt ing geniculocort ical f ibers or commissural f ibers connect ing
homot ropic (corresponding) primary audit ory cort ices[56, 452] . When t he def ect
is severe, pat ient s may complain t hat people sound as if t hey are speaking a
f oreign language. By using lip-reading, t hese pat ient s can improve t heir
perf ormance, but not by increasing t he sound volume. O ne such pat ient , unable
t o underst and his w if e's normal speech, disliked t he sound of t he t elevision set
and compelled her t o t urn t he volume so low t hat she herself could not
underst and w hat w as being said. Rarely, w hen t emporal lobe lesions are
asymmet ric, great er impairment of sound and w ord recognit ion may be det ect ed
in t he ear cont ralat eral t o t he larger lesion[9] . Pat ient s w it h larger lesions of t he
lef t hemisphere may have great er diff icult y in dist inguishing w ords, w hereas
predominant ly right -hemisphere lesions may cause great er impairment in t he
discriminat ion of nonverbal sounds, including music. Poor recognit ion of w ords
accompanied by almost normal reading and speech may occasionally appear in
t he process of recovery f rom a sizable unilat eral lesion in t he dominant superior
t emporal gyrus involving t he audit ory associat ion cort ex (Wernicke's area). I n
such cases t he receding Wernicke's aphasia gives w ay t o almost normal
language abilit y, t aint ed by an occasional paraphasic error, but underst anding of
t he spoken w ord remains markedly impaired, part icularly w hen short sent ences
of a somew hat complex synt act ic st ruct ure are given t o t he pat ient in a t est
sit uat ion.
Sensory Amusia
This t erm ref ers t o t he inabilit y t o appreciat e various charact erist ics of heard
music[ 19] . Right -hemisphere lesions result in impairment of appreciat ion of pit ch,
t imbre, and rhyt hm, w hereas lef t -hemispheric lesions mainly aff ect appreciat ion
of lyrics. The right cerebral hemisphere is primary in represent ing melody in
t erms of it s global cont our, w hereas t he lef t hemisphere is primary in f illing in
t he int ervallic st ruct ure[365] . The degree of musical sophist icat ion of t he pat ient
may be ref lect ed in t he lat eralizat ion of t he cort ex used t o process music. The
lef t hemisphere seems t o play a great er role in t he appreciat ion of music by
musically t rained individuals, w ho may use a more analyt ic st rat egy t o ident if y a
musical composit ion. The superior t emporal gyrus is especially import ant in
melody processing.
Posterior Aphasias
Most cort ical lef t -hemisphere lesions leading t o impaired processing of audit ory
inf ormat ion cause a language dist urbance, t hat is, an aphasi a. Aphasia is a
disorder of linguist ic processing charact erized by a dist urbance in t he
comprehension and f ormulat ion of language caused by dysf unct ion in specif ic
brain regions[96] . Aphasia can compromise
mult iple aspect s of language, including synt ax (t he grammat ic st ruct ure of

sent ences), t he lexicon (t he collect ion of w ords t hat denot e meanings), and t he
morphology of w ords (t he combinat ion of individual speech sounds, know n as
phonemes, int o t he smallest meaningf ul unit s of a w ord, know n as morphemes)
[ 96] . The t ype of aphasic dist urbance depends on t he f ollow ing:
1. The cort ical represent at ion of t he analysis of language-relat ed audit ory

st imuli in a part icular pat ient . I n most right -handed persons and in more t han
t w o-t hirds of lef t -handers, t he lef t superior t emporal gyrus and t he
neighboring inf erior pariet al lobule play t he great est role in t his analysis. I n
some right -handed persons, t he right hemisphere is dominant f or
language[ 227] . I n some lef t -handed individuals, t he lef t hemisphere may be
dominant f or comprehension and t he right hemisphere dominant f or speech
out put [ 343] .
2. The locat ion of t he lesion. Lesions cent ered in t he post erior t w o-t hirds of t he
superior t emporal gyrus aff ect ing t he audit ory associat ion cort ex (area 22 of
Brodmann, or Wernicke's area) t end t o cause t he great est impairment of
audit ory comprehension of language, even w hen reading may be only mildly
aff ect ed. The neighboring area of t he middle t emporal gyrus also
part icipat es in language processing. Theref ore, Werni cke's aphasi a is most
of t en due t o damage t o t he post erior sect or of Wernicke's area and, in many
inst ances, area 37, areas 39 and 40, or all t hree are also involved [96, 254,
333, 414, 415] . Pat ient s w it h Wernicke's aphasia are unable t o repeat
sent ences correct ly, t o assemble phonemes correct ly, and t o name t hings
properly, but t heir speech is f luent (eff ort less, melodic, w ell w oven, and
produced at a normal or even f ast er rat e) [96, 250, 333] . Also, t he cont ent
of speech is of t en unint elligible because of f requent errors in phoneme and
w ord choice, and comprehension of sent ences spoken by ot hers is
impaired[ 96] . These pat ient s make f requent lit eral and phonemic paraphasic
errors (w ord subst it ut ions). Depending on t heir premorbid personalit ies,
t hese pat ient s are of t en anxious, agit at ed, and even paranoid, perhaps
because of t heir inabilit y t o underst and w hat ot hers are saying. Pat ient s w it h
Wernicke's aphasia are of t en misdiagnosed as having a psychiat ric disorder,
especially as associat ed hemiparesis and sensory loss may be absent or
mild. The more post erior t he locat ion of t he lesion, in t he angular gyrus
region, t he more pronounced is t he alexia and anomia f or visually recognized
object s.
Wernicke's aphasia most commonly occurs due t o inf arct ion in t he
dist ribut ion of t he inf erior division of t he middle cerebral art ery but may also
occur w it h t umor, abscess, or hemorrhage, especially w hen post erior
put aminal bleeds ext end int o t he ist hmus of t he t emporal lobe. Seizures can
produce not only brief episodes of aphasia, but also aphasia last ing days or
even long periods of t ime, including t he Landau-Kleff ner syndrome[217, 449] .
Alt hough damage t o Wernicke's area disrupt s audit ory comprehension, t his
area is not t he “cent er” in w hich audit ory comprehension t akes place but is
rat her a processor of speech sounds t hat allow s sounds t o be mapped as
w ords and t o be used subsequent ly t o evoke concept ual meaning[96] .
Funct ional brain st udies have document ed t hat t he lef t post erior superior
t emporal gyrus is implicat ed in t he preat t ent ive det ect ion of acoust ic
changes in speech as w ell as nonspeech st imuli, w hereas cort ical areas
around it , such as t he lef t supramarginal and middle t emporal gyri, are more
specif ically engaged in t he det ect ion of changes in phonologic unit s [41, 77,
326] . Novel w ords act ivat e t he ant erior hippocampal region[404] . The
f usif orm gyri, part icularly on t he lef t , act ively part icipat e in semant ic t asks,
perhaps providing lexical inf ormat ion[424] . Audit ory comprehension,
t heref ore, involves numerous diff use cort ical areas t hat are “dow nst ream”
f rom Wernicke's area. Clinical observat ions suggest t hat Wernicke's area
lies at t he semant ic-lexical pole of t he language net w ork and t hat t his area
appears t o provide, at t he input st age, an ent ry point f or t he conversion of
audit ory sequences int o neural w ord represent at ions (Fig. 20-12)[ 325] .
Broca's area in t he f ront al operculum (see subsequent t ext ), on t he ot her
hand, lies at t he synt act ic-art iculat ory pole of t he language net w ork, w hich
provides a syst em f or t he t ransf ormat ion of neural w ord represent at ions
(originat ing f rom Wernicke's area but also f rom ot her brain areas) int o
corresponding art iculat ory sequences (Fig. 20-12) [67, 135, 325] . I f
Wernicke's area leads t o meaning-appropriat e cont ent w ords, Broca's area
inf luences how t o order and ut t er t hem in t he most meaning-appropriat e
f orm[ 325] . Neuroimaging st udies have suggest ed t hat t he localizat ion of a
lexicon (i. e. , a cort ical area of specializat ion) f or spoken w ord recognit ion
exist s in t he middle part of t he lef t superior and middle t emporal gyri and
t hat a lexicon f or w rit t en w ord recognit ion exist s in t he post erior part of t he
lef t middle t emporal gyrus[225] .
An aphasic syndrome similar t o Wernicke's aphasia but w it h associat ed

hemiparesis has been described w it h inf arct s involving t he head of t he lef t
caudat e nucleus and nearby w hit e mat t er in t he ant erior limb of t he int ernal
capsule [60, 96, 100, 163, 342] . These st rokes occur by occlusion of t he
st em of t he middle cerebral art ery, w hich blocks t he f low t o smaller lent icular
branches. Aphasia w it h lesions in t his dist ribut ion est ablish t hat t he region of
t he head of t he lef t caudat e and surrounding w hit e mat t er is essent ial f or
language processing; t his region int erconnect s w it h t he audit ory cort ex and
may be relat ed t o aut omat ic processing of f requent ly used sent ence
st ruct ures[ 96] . There is a cont roversy w het her subcort ical lesions can cause
t rue aphasia [161, 341] . I n cases of ischemia w it h diminished perf usion of
bot h t he basal ganglia and t he t emporal cort ex, improvement of cort ical
perf usion has been f ollow ed by recovery f rom t he aphasia[215] . How ever, at
least acut ely, ant erior put aminal hemorrhages can give rise t o a t rue global
aphasia, w it h impaired repet it ion. As discussed in Chapt er 18, inf arct ions
involving some lef t t halamic nuclei, especially t he ant erolat eral nuclei, may
also cause aphasia charact erized by f luent speech w it h preserved repet it ion,
t hereby conf irming t hat t he lef t t halamus is involved in speech and language
f unct ions[ 188] .
Damage t o t he lef t ant erior t emporal cort ices in areas 21, 20, and 38 impairs
t he abilit y t o
ret rieve w ords but does not cause any grammat ic, phonemic, or phonet ic
diff icult y (i. e. , such lesions cause pure naming def ect s)[ 96] . When t he
damage is conf ined t o t he lef t t emporal pole (area 38), pat ient s may have a
def ect in t he abilit y t o ret rieve proper nouns (t he unique names of unique
places and persons) but not common nouns (t he names f or nonunique
object s) [96, 165, 416] . When t he lesions involve t he cort ices of areas 20
and 21 in t he lef t hemisphere, t he def ect encompasses t he abilit y t o ret rieve
bot h proper and common nouns. Wit h t hese lesions, t he abilit y t o ret rieve
ot her cat egories of w ords (verbs, adject ives, and grammat ic w ords) is not
compromised[ 96] . Theref ore, t he lef t ant erior t emporal cort ices cont ain
neural syst ems t hat hold t he key t o gaining access t o w ords t hat go w it h
object s, places, or persons but not t o w ords t hat convey t he qualit ies of
t hose ent it ies or t heir act ions or relat ionships[96] . Condit ions such as st roke,
t rauma, herpes encephalit is, Alzheimer's disease, Pick's disease, and lobar
at rophy may of t en damage t hese areas [14, 95, 96, 187, 311, 432] . The
import ance of t he lef t t emporal cort ices in t he abilit y t o name object s is also
support ed by st udies t hat show t hat such naming diff icult ies occur w it h
elect rical st imulat ion of t he lef t t emporal lobe during surgery f or
epilepsy[ 352] . How ever, naming of concret e object s act ivat es ext ensive
areas of t he lef t hemisphere, out side t he classical perisylvian speech
area[ 103] .
Lesions circumscribed t o t he inf erior t emporal gyrus give rise t o word-
sel ecti on anomi a. Pat ient s cannot remember t he name of an object
present ed t o t hem, and cueing does not help, but t hey can consist ent ly
choose t he appropriat e object f rom an array w hen t hey hear it s name. Bot h
name ret rieval and name recognit ion are impaired w it h lesions of Wernicke's
area (semanti c anomi a).
3. The size of t he lesion. A large lesion involving t he superior and middle
t emporal gyri and t he inf erior pariet al lobule is most likely t o cause a severe
def icit in t he comprehension of spoken and w rit t en language. I n such cases,
t he w ords t he pat ient hears are devoid of semant ic meaning (semant ic
aphasia); he or she gat hers no inf ormat ion f rom t hem. Similarly, t he pat ient 's
ut t erances consist of semant ically meaningless nonw ords (neol ogi sms) or
have a t hin connect ion t o t he object t hey are meant t o signif y (paraphasi as).
This connect ion is generally cat egoric (verbal or semant ic) (e. g. , “t able” f or
“chair”) w it h post erior perisylvian lesions and phonologic (lit eral) (e. g. ,
“let t er” f or “ladder”) w it h lesions in Broca's area. Pat ient s w it h large
post erior perisylvian lesions w rit e nonsensical w ords or sent ences and
cannot name object s appropriat ely (Fig. 20-13).
Smaller, dest ruct ive lesions—such as inf arct s circumscribed t o t he
supramarginal gyrus (area 40) or t he primary audit ory cort ex (areas 41 and
42), —or large post erior perisylvian lesions, such as t umors t hat displace but
spare neurons, cause so-called conducti on aphasi a. Pat ient s w it h conduct ion
aphasia speak int elligibly and comprehend w ell enough t o maint ain a normal
conversat ion, but t heir abilit y t o repeat is impaired, and t hey of t en make
paraphasic errors[96, 250] . Conduct ion aphasia and ot her semant ic
impairment s may result not only f rom cort ical lesions, but also f rom lesions
in an immediat ely subcort ical w hit e mat t er t ract t hat has t w o segment s: a
post erior one, joining t he superior t emporal gyrus w it h t he supramarginal
gyrus, and an ant erior one, f rom t he supramarginal gyrus t o Broca's area in
t he inf erior f ront al gyrus[73, 130] . Dejerine already described how t he more
superf icial f ibers of t he arcuat e f asciculus w ere short associat ion f ibers,
joining adjacent gyri[114] . O nly t he deeper ones spanned several gyri.
The combinat ion of conduct ion aphasia and cont ralat eral hemianest hesia
indicat es a w hit e mat t er lesion subjacent t o inf erior pariet al and post erior
t emporal cort ices t hat likely int errupt s t halamocort ical connect ions[229] .
Conduct ion aphasia has also been described in lef t -handed individuals w it h
lef t t emporopariet al lesions aff ect ing Wernicke's area and in a right -handed
man w it h a right t emporopariet al inf arct [321] .
4. The t ime allow ed f or recovery af t er an acut e lesion. The severe impairment
of language comprehension (semant ic or Wernicke's aphasia) t hat f ollow s a
large vascular lesion t ends t o improve in subsequent w eeks and mont hs (Fig.
20-14). More and more w ords and sent ences regain t heir inf ormat ive value,
and t he def icit may f inally resemble conduct ion aphasia. Persist ent def icit s in
sent ence repet it ion (i. e. , t hose last ing 6 mont hs or longer) occur most
consist ent ly w it h lesions dest roying part or all of Wernicke's area[415] . The
mechanisms of language recovery are being clarif ied w it h t he help of
neuroimaging. The act ivat ion of regions near t he damaged cort ex and t he
homot opic areas of t he cont ralat eral hemisphere bot h cont ribut e t o language
recovery[ 44, 46] .
FI G URE 20-12 Relat ionships bet w een brain sit es, language f unct ion, and
aphasia subt ypes. Thicker lines indicat e more int ense connect ivit y. Broken
lines indicat e neural lesions t hat lead t o various language dist urbances. AP =
aphemi a; APR = aprosodi a; B = Broca's area and Broca's aphasia; CA =
central or conduct ion aphasia; DYS = dysarthri a; PWD = pure w ord
deaf ness; TMA = transcorti cal mot or aphasia; TSA = transcorti cal sensory
aphasia; W = Werni cke's area and Wernicke's aphasia. (Reprint ed w it h
permission f rom Mesulam MM. Large-scale neurocognit ive net w orks and
dist ribut ed processing f or at t ent ion, language, and memory. Ann Neurol
1990; 28: 597–613. )
Tran scortical Sen sory Aph asia

Some pat ient s can repeat w ords w ell but are unable t o underst and
t he meaning of t he spoken or w rit t en w ord. They may repeat a command f rom

t he examiner (echolalia) and yet f ail t o f ollow it . O t her audit ory inf ormat ion is
also missed, despit e t he abilit y t o repeat t he very sent ence of w hich t he meaning
is not quit e grasped. This syndrome, t ermed transcorti cal sensory aphasi a, is
most of t en due t o lesions in t he post erior middle t emporal gyrus (area 37),
angular gyrus (area 39), w hit e mat t er of t he t emporal ist hmus, and post erior
perivent ricular area[96, 246] and, except f or spared repet it ion, is an analog of
Wernicke's aphasia. Lesions in t he t halamus, lef t mesial f ront opariet al region, or
inf erolat eral aspect of bot h t emporal lobes may cause a similar syndrome[304,
390] . I t has lit t le localizing value and is most of t en caused by ischemic lesions in
t he dist ribut ion of t he middle cerebral or post erior cerebral art eries, or in t he
w at ershed bet w een t he t w o vascular t errit ories.
FI G URE 20-13 Jargon w rit ing by a 59-year-old, lef t -handed man w it h a large
lef t -hemispheric perisylvian inf arct . The dict at ed t ext is print ed beside t he
pat ient 's w rit ing. He could copy (“t his is a hospit al”) but not read print ed
w ords. His oral language w as pract ically normal.
The language prof ile in pat ient s w it h Alzheimer's disease may closely resemble a
t ranscort ical sensory aphasia[340] .
The Bost on anat omo-clinical classif icat ion of aphasias based on t he pat ient 's
spont aneous speech, comprehension, naming, and repet it ion has w on
w idespread accept ance (Table 20-3)[ 35] .
Posterior Aprosodia
I t has been proposed t hat just as t he lef t (dominant ) hemisphere plays t he
great er role in t he analysis of t he synt act ic component s of language,
corresponding areas of t he
right hemisphere are concerned w it h t he emot ional aspect s of language

(prosody, or aff ect ive int onat ion of spoken language, and emot ional gest uring)
[ 391] . Lesions in t he right post erior t emporopariet al region may result in poor
percept ion of t he emot ional overt ones of spoken language (sensory aprosodia).
These pat ient s have impaired prosodic-aff ect ive comprehension and repet it ion
(but relat ively spared expression and spont aneous aff ect ive prosodic variat ion
and gest ure) and impaired ident if icat ion of emot ional gest uring[107] . Sensory
aprosodia may be an acut e marker of isolat ed inf arct ion of t he inf erior division of
t he right middle cerebral art ery[107] and has also been described associat ed
w it h lef t hemiparesis w it h ischemic inf arct ion of t he right t halamus and post erior
limb of t he int ernal capsule (analogous t o Wernicke's aphasia w it h right
hemiparesis described w it h lef t subcort ical injury)[ 489] . Pat ient s w it h acut e
st roke causing comprehension emot ional aprosody show a higher f requency of
ext inct ion on double simult aneous st imulat ion, anosognosia, and def icit s in f acial
emot ion comprehension[440] . These pat ient s w it h st roke also show a higher
f requency of right -hemisphere lesions involving t he basal ganglia and t he

t emporopariet al cort ex and more severe f ront al and diencephalic at rophy.
Pat ient s w it h right -hemisphere damage are of t en impaired in t heir capacit y t o
judge t he emot ional cont ent of sent ences depict ing f acial, prosodic, and gest ural
expression even w hen t hey can perf orm normally in t heir abilit y t o inf er t he
emot ion conveyed by sent ences describing sit uat ions, suggest ing a disrupt ion of
nonverbal communicat ive represent at ions[47] .
FI G URE 20-14 Clinical manif est at ions of recent versus old lesions in t he
post erolat eral aspect of t he lef t hemisphere. Wit h similar ext ent lesions, t w o
pat ient s had a very diff erent clinical pict ure. Vert ical hat ching indicat es t he
ext ent of an inf arct developed 2 w eeks previously in a 57-year-old man. He
had a severe w ord comprehension diff icult y, alexia w it h agraphia, and a
semant ic anomia. He repeat ed w ords inaccurat ely. His spont aneous speech
w as uninf ormat ive and marred by neologisms. By cont rast , t he 62-year-old
man w hose 1-year-old inf arct involved t he area st ippled in t he f igure
underst ood conversat ional speech w ell, could w rit e, and spoke w it h mild
circumst ant ialit y and occasional paraphasic errors. He st ill missed t he
meaning of some dict at ed w ords and underst ood t elevision poorly.
TABLE 20-3 Classification of the Apha
Type of
Fluency Com prehension Repetition Na
Aphasia
Broca's ↓ Good ↓ ↓
W ernicke's Good ↓ ↓ ↓
Conduction Good Good ↓ ↓
Transcortical Ma
↓ Good Good
motor no
Transcortical Us
Good ↓ Good
sensory no
Anomic Good Good Good ↓
Global ↓ ↓ ↓ ↓
Lesions of t he right hemisphere may impair a language abilit y know n as

di scourse, t he skill w it h w hich one can organize a narrat ive (e. g. , t ell a st ory,
make a joke, or w rit e a let t er)[ 96, 444] . Right -hemisphere damage may also
impair t he pat ient 's abilit y t o appreciat e a st ory or get t he point of a joke[96] .
Disturbances of Somatosensory Perception

Elemental Somatosensory Disturbances
Lesions of t he post cent ral gyrus cause cont ralat eral impairment in t he percept ion
of size and shape by palpat ion. As a result , t he ident it y of t he palpat ed object
remains unknow n (astereognosi s). Such impairment , w hich is great est in t he limb
represent ed in t he lesioned area (Fig. 20-6), also aff ect s t w o-point
discriminat ion and graphest hesia (t he abilit y t o recognize a let t er or digit t raced
on t he pat ient 's skin). A pin-prick is also perceived as less sharp on t he side
cont ralat eral t o an acut e pariet al lobe lesion. Sensory loss w it h pariet al lesions
t ends t o be localized t o t he dist al port ion of t he limbs, w hich have t he largest
cort ical represent at ion and are almost exclusively innervat ed by t he cont ralat eral
hemisphere. Parest hesias, usually of a t ingling qualit y, may occur in t he limb
represent ed in an area of t he post cent ral gyrus aff ect ed by ischemia or epilept ic
act ivit y (sensory seizure). I t has been post ulat ed t hat lesions of t he pariet al
operculum (superior lip of t he Sylvian f issure corresponding t o t he secondary
somat osensory area) may cause a pseudot halamic syndrome, w it h pronounced
impairment in t he percept ion of pain and t emperat ure in t he acut e st age and a
delayed “t halamic” t ype of pain[58] . How ever, delayed pain and parest hesia
occur f requent ly af t er deep or large pariet al lesions. Persist ent impairment of
t act ile object recognit ion (t act ile agnosia) can also f ollow lesions of t he
secondary sensory area, in t he inf erior ext ent of t he somat osensory cort ex,
abut t ing t he Sylvian f issure, w hereas lesions of t he supplement ary mot or cort ex,
in t he medial aspect of t he pariet al lobe (precuneus) generally cause more
severe but t ransient disrupt ion of somest het ic processing[70] .
Pariet al st roke can cause diff erent sensory syndromes depending on t he
t opography of t he underlying lesion[24] . Alt hough sensory loss may be t he only
f inding, t hey never present as a “pure sensory st roke” involving f ace, arm, leg,
and t runk t oget her. I n a st udy of pat ient s w it h acut e pariet al st roke w it h
hemisensory dist urbances (but no visual f ield def icit and no or only slight mot or
w eakness), w it hout t halamic involvement on CT scan or MRI , t hree main sensory
syndromes w ere f ound[24] .
1. The pseudothal ami c sensory syndrome consist s of a f aciobrachiocrural

impairment of element ary sensat ion (t ouch, pain, t emperat ure, and
vibrat ion). All pat ient s have an inf erior–ant erior pariet al st roke involving t he
pariet al operculum, post erior insula, and, in most pat ient s, underlying w hit e
mat t er.
2. The corti cal sensory syndrome consist s of an isolat ed loss of discriminat ive
sensat ion (st ereognosis, graphest hesia, posit ion sense) involving one or t w o
part s of t he body. These pat ient s show a superior–post erior pariet al st roke.
3. The atypi cal sensory syndrome consist s of a sensory loss involving all
modalit ies of sensat ion in a part ial dist ribut ion. Pariet al lesions of varied
t opography are responsible f or t his clinical pict ure, w hich probably
represent s a minor variant of t he t w o previous sensory syndromes.
Disturbances of “Body Schema” and Spatial

Relationships
Bot h pariet al lobes mediat e t he orient ing response t o a sensory st imulus in
space. Each hemisphere mediat es act ivit y in t he cont ralat eral hemispace
independent of t he sensory half -f ield of t he ext remit y used. The right
hemisphere, how ever, seems t o play a great er role in t his at t ent ional t ask,
mediat ing at t ent ion t o st imuli f rom bot h hemispaces, w hereas t he lef t pariet al
lobe is mainly concerned w it h st imuli delivered t o t he right hemispace [208, 209,
253, 324, 486] . As a consequence, right -hemisphere lesions t end t o cause
hemineglect much more readily t han lef t -sided lesions. Perhaps on t he same
basis, large right pariet al or f ront opariet al lesions are of t en accompanied by
anosognosia in w hich t he pat ient denies an obvious lef t hemiparesis or even
being sick at all[134] . Denial of hemiplegia is of t en associat ed w it h neglect , and
perhaps pat ient s do not recognize t hat t hey are hemiplegic because t hey have
personal neglect [209] . St ill ot her pat ient s f ail t o recognize t he hemiplegic limbs
as belonging t o t hem (aut ot opagnosia) and conf abulat e w hen asked w hom t hey
belong t o (t hey of t en ascribe t hem t o t he examiner: somat oparaphrenia).
Verbally acknow ledging a problem but f ailing t o be concerned is called
anosodi aphori a[ 209] . Rarely, pat ient s may
report a supernumerary phant om limb (phant om t hird limb or “t hree arms”) af t er

right -hemisphere st roke; t he subject ive realit y of t his “t hird arm” may cause t he
pat ient considerable dist ress[197] . A pat ient w it h a medial pariet al injury
report ed t he t ransient f eeling of having f our legs[473] .
Pat ient s w it h persist ent anosognosia f or hemiplegia af t er right -hemisphere
st roke invariably have severe lef t hemisensory loss and usually have severe lef t
spat ial neglect [281] . These pat ient s are almost alw ays apat het ic; t heir t hought
lacks direct ion, clarit y, and f lexibilit y, and t hey have at least moderat e
impairment of int ellect and memory. Right -hemisphere st rokes are usually large
and alw ays aff ect t he cent ral gyri or t heir t halamic connect ions and capsular
pat hw ays. I n addit ion, t here is evidence of at least mild lef t -hemisphere damage,
most commonly caused by age-relat ed at rophy. The pat hogenesis of
anosognosia f or hemiplegia may involve f ailure t o discover paralysis because
propriocept ive mechanisms t hat ordinarily inf orm an individual about t he posit ion
and movement of limbs are damaged, and t he pat ient , because of addit ional
cognit ive def ect s, lacks t he capacit y t o make t he necessary observat ions and
inf erences t o diagnose t he paralysis[281] . Anosognosia may be associat ed w it h
a neglect syndrome and major depression; t heref ore, t he presence of
anosognosia does not preclude t he recognit ion of emot ional impairment [439] .
Pat ient s w it h dominant pariet al (especially supramarginal gyrus) or bilat eral
pariet al lesions may demonst rat e asymbolia f or pain in w hich t he pat ient does
not react appropriat ely t o pain and may indeed smile during painf ul st imuli[156] .
Sudden onset of conf usion w it hout agit at ion and a pronounced disorient at ion f or
place disproport ionat e t o t he rest of t he pat ient 's behavior have been described
as signs of right pariet al (or right pref ront al) inf arct ion[149, 323] . Right pariet al
lesions cause impairment of t asks requiring apprehension of spat ial relat ions,
independent of sensory modalit y. Visual or t act ile localizat ion of point s in space
and judgment of direct ion and dist ance are def ect ive. Pat ient s w it h right pariet al
lobe lesions t end t o misplace t he cit ies on a map and t o get lost in f amiliar
surroundings (loss of t opographic memory); t his last t ype of t opographic
disorient at ion is more common w it h bilat eral pariet al lesions.
When st imulat ed on t he side cont ralat eral t o a hemispheral (especially pariet al)
lesion, pat ient s may demonst rat e al l esthesi a, in w hich t hey misplace t he locat ion
of t he st imulus t o t he normal side[209] . Most commonly pat ient s w it h allest hesia
incorrect ly ident if y lef t -sided st imuli as coming f rom t he right side. Pat ient s w it h
al l oki nesi a respond w it h t he w rong limb or move in t he w rong direct ion.
Pat ient s w it h pariet al lesions may demonst rat e hemi somatognosi a[ 156] , w hich is
a unilat eral mispercept ion of one's ow n body. This may be conscious (t he pat ient
f eels like a hemiamput ee) or unconscious (t he pat ient behaves as a
hemiamput ee). The conscious f orm is usually t ransient , of subcort ical origin,
unimodal, nonlat eralizing, and seen w it h paroxysmal disease, such as migraine or
seizure disorder. The unconscious f orm is usually permanent , of nondominant
pariet al origin, mult imodal (i. e. , associat ed w it h neglect , anosognosia,
ast ereognosis, and const ruct ional apraxia), and due t o a st ruct ural lesion (e. g. ,
st roke). I n t his f orm, pat ient s have no concern about one-half of t he body and
t end t o leave t he arm dangling, t o not cover half t he body, and t o not shave half
t he f ace. O ccasionally, paroxysmal disorders (e. g. , epilepsy, migraine, drug
abuse) may result in macro- or microsomat ognosia in w hich t he pat ient perceives
part of t he body or t he w hole body as being abnormally large or small[155] . This
is t hought t o be due t o irrit at ion of t he lef t or right pariet o-t emporo-occipit al
regions.
Verbal asomat ognosia is a f orm of neglect in w hich t he pat ient denies ow nership
of a limb cont ralat eral t o a brain lesion (vs. nonverbal asomat ognosia, w hich is a
simple f ailure t o dress an arm or shave half of t he f ace)[ 139] . Verbal
asomat ognosia is caused by lesions of t he right supramarginal gyrus and it s
subcort ical associat ions w it hin t he post erior corona radiat a[139] .
Some of t hese percept ual diff icult ies probably underlie t he impaired mot or
perf ormance (apraxia), w hich is out of proport ion t o t he primary mot or or
sensory def icit , of pat ient s w it h right pariet al lesions. Const ruct ional apraxia, t he
inabilit y t o put t oget her t he diff erent part s of a spat ial array, is a charact erist ic
disorder. Constructi onal apraxi a due t o right -sided lesions result s in draw ings
t hat maint ain t he st ruct ural complexit y of t he model but w hich have impaired
spat ial relat ionships among part s of t he model, t end t o neglect t he lef t half of
t he model, and t end t o be orient ed diagonally on t he paper[168] . Depending on
t he degree of t heir impairment , t hese pat ient s cannot build a block design t hat
mat ches a given sample, copy t w o- or t hree-dimensional f igures, or draw t w o- or
t hree-dimensional object s (Fig. 20-15). Hemispat ial neglect is of t en conspicuous,
f or inst ance, w hen t he pat ient leaves out all t he lef t -sided numbers on t he f ace
of a clock or t he pet als on t he lef t side of t he daisy he or she has been asked t o
draw. Pat ient s w it h hemispat ial neglect may have diff icult y w it h bisect ing a line
and may read part of a w ord or part of a sent ence (paralexia) (e. g. , “cow boy”
is read as “boy”). Pat ient s w it h lef t -sided lesions may also have diff icult y w it h
draw ings in t hat t hey draw slow ly and w it h diff icult y, oversimplif y t he design, and
t end t o t race lines perpendicular t o t hose already draw n, result ing in an
increased number of right angles (Fig. 20-15). Pat ient s w it h more diff use
(nonf ocal) cort ical damage (e. g. , Alzheimer's disease) may place t heir draw ings
close t o t he model or superimpose t he copy on t he model (Mayer-G ross closing-
in phenomenon) (Fig. 20-15).
FI G URE 20-15 Examples of draw ings made by pat ient s w it h lef t -sided and
right -sided cerebral lesions and a pat ient w it h diff use cort ical dysf unct ion
f rom Alzheimer's disease. The lef t -sided cases produce oversimplif ied copies
w it h great diff icult y, w hereas t he right -sided cases neglect t he lef t half of t he
space and f ail t o reproduce t he proper spat ial relat ions among t he part s of
t he model draw ing. “Closing-in” phenomenon is illust rat ed, in w hich t he
pat ient places t he draw ing close t o t he model and superimposes t he copy on
t he model.
Dressing Apraxia
I mpaired t act ile and visuospat ial coordinat ion plus a degree of hemineglect may
explain w hy some pat ient s w it h right pariet al lesions have a st riking diff icult y
donning t heir clot hes. Hemineglect is obvious w hen t he pat ient leaves t he lef t
side of t he body uncovered and disheveled.
Finger Agnosia, Right–Left Disorientation, Agraphia,

and Acalculia
G erst mann described t he associat ion of t hese f our signs (G erstmann's
syndrome) as charact erist ic of lesions in t he angular and supramarginal gyri of
t he dominant hemisphere[37] . The lesion can involve t he subangular w hit e
mat t er, aff ect ing t he f orceps of t he splenium of t he corpus callosum[307] . A
pat ient w it h t he complet e t et rad had a def icit in t he t ranslat ion, rot at ion, or ot her
t ransf ormat ions of visual ment al images[307] . How ever, cases have been
report ed in w hich pat ient s w it h all f our component s of t he syndrome proved t o
have an int act angular gyrus on necropsy examinat ion[211] . O t her st udies have
show n a st rong correlat ion of f inger agnosia and right –lef t disorient at ion w it h
impairment of language comprehension in unilat eral lesions. This holds not only
f or perf ormances in w hich underst anding of t he labels ri ght and l ef t is required
but also f or nonverbal perf ormances, such as imit at ion[36] . Nondominant pariet al
lesions may give rise t o some f orms of right –lef t disorient at ion, specif ically
misident if icat ion of body part s of a conf ront ing individual and t he f ailure t o
imit at e crossed movement s of t he examiner (e. g. , lef t hand on right ear).
I mpairment in t hese t asks may be based on visuospat ial disabilit y[36] .
Agraphia
I nabilit y t o w rit e properly (agraphia) accompanies all ot her language
dist urbances. The charact erist ics of t hese f orms of agraphia are described in t he
paragraphs dealing w it h aphasia. The associat ion of agraphia w it h alexia in
angular gyrus lesions aff ect ing t he dominant hemisphere w as discussed in t he
sect ion on alexia. This w rit ing dist urbance has been called pari etal agraphi a
because it result s f rom lesions of t he inf erior pariet al lobule. Marked diff icult y
w it h spelling out and put t ing t oget her spelled-out w ords accompanies t his t ype of
agraphia. Apraxia is almost alw ays present ; anomia is common. Pariet al
agraphia is charact erized by impairment in t he draw ing of let t ers, relat ive
preservat ion of t he synt act ic st ruct ure of sent ences, and parallel impairment of
all w rit ing modalit ies (spont aneous w rit ing, w rit ing t o dict at ion, copying). By
cont rast , in aphasic agraphia, copying abilit y is usually preserved. Pariet al
agraphia is not merely a direct expression of hand apraxia because spelling
using block let t ers is also impaired. The relat ive severit y of agraphia and alexia
varies w it h t he locat ion of t he lesion; alexia predominat es w it h
t emporo-occipit al lesions, and agraphia is more prominent w it h pariet o-occipit al

lesions[ 296] .
Apract ic agraphia is an impairment in w rit ing in w hich t he act ual ort hographic
product ion of let t ers and w ords is abnormal despit e normal sensorimot or
f unct ion, visual f eedback, and w ord and let t er know ledge[6] . Apract ic agraphia is
probably one of several relat ed clinical disorders t hat are due t o t he loss of
spat ially and kinest het ically modulat ed movement s. I t is produced by lesions in
t he superior pariet al lobule, usually in t he hemisphere dominant f or language[6] .
Writ ing impairment may occur w it h ot her cent ral nervous syst em lesions[32] . For
example, visuospat ial agraphia may occur w it h lesions of t he nondominant
t emporopariet al junct ion. These pat ient s neglect t he lef t side of t he paper w hen
w rit ing and t end t o conf ine t heir w rit ing t o progressively smaller port ions of t he
right side of t he page. They have abnormal spacing bet w een w ords and t end t o
slant t he lines t ow ard t he t op or bot t om of t he page. Writ ing dist urbances may
also occur f rom mot or paresis (paret ic agraphia), f rom Parkinson's disease
(micrographia w it h t he let t ers becoming progressively smaller and more crow ded
as t he w rit ing proceeds), and f rom hyperkinet ic movement disorders
(hyperkinet ic agraphia). Micrographia may also occur w it h dominant pariet al lobe
w hit e mat t er lesions[413] . Echographia (compulsive copying of w ords and
phrases) may occur w it h dominant f ront o-t emporal lesions and w it h psychiat ric
dist urbances, w hereas paligraphia (w rit t en repet it ion of w ords and phrases) is
seen w it h diff use or bilat eral cort ical disease[32] . Perseverat ive agraphia
(cont inuat ion or recurrence of w rit ing w it hout appropriat e st imulus) may occur
w it h lesions of t he f ront al lobe, w it h diff use cort ical disease (e. g. , Alzheimer's
disease), and in pat ient s w it h aphasia[296] . Coprographia (compulsive w rit ing of
prof anit ies) has been described w it h Touret t e's syndrome. Hypergraphia
(excessive w rit ing in general) may occur w it h schizophrenia and may also be
seen as part of an int erict al personalit y disorder in pat ient s w it h complex part ial
seizures (especially w it h nondominant epilept ic f oci)[ 484] . Hypergraphia may
also f ollow acut e right cerebral st roke or met ast at ic t umor[232, 491] .
Acalculia
Lef t pariet o-occipit al lesions t hat cause aphasia of t en cause diff icult y in
perf orming simple arit hmet ic calculat ions. Ant erior f ront al lesions impair t he
abilit y t o solve problems in w hich more t han one st ep is involved (e. g. , dist ribut e
six books bet w een t w o shelves in such a w ay t hat one shelf cont ains t w ice as
many books as t he ot her) or calculat ions in an open-ended series, in w hich t he
pat ient ut t ers perseverat ions af t er an accurat e answ er (e. g. , 100 - 7 = 93, -7 =
83, -7 =73).
Simple calculat ions may be impaired because of t he f ollow ing:
1. Alexia or agraphia f or numbers. Pat ient s w it h lef t t emporal lesions may be

able t o calculat e as long as t hey can use a paper t o w rit e dow n t he
calculat ions, but t hey cannot handle calculat ions given orally or t hose t hat
require verbal carryover, even silent , of numbers.
2. I mpaired spat ial organizat ion of numbers (spat ial acalculia), ref lect ed by
misalignment of digit s, visual neglect (e. g. , 252 read as 52), inversion of
digit s (e. g. , 9 int erpret ed as 6), reversal errors (e. g. , 12 int erpret ed as 21),
and inabilit y t o maint ain t he decimal place. I n a pat ient w it hout generalized
ment al det eriorat ion or aphasia, t his t ype of spat ial acalculia suggest s a
post -Rolandic lesion in t he right hemisphere[280] . Pat ient s w it h pariet o-
occipit al lesions of eit her hemisphere may underst and t he value of single
digit s yet be unable t o read and w rit e compound numbers. They read 19 as 1
and 9. They may est imat e t he size of a FI G URE rom t he value of t he
individual numbers; t heref ore t hey consider 2, 989 larger t han 5, 010.
3. Pure anarit hmet ria, t he inabilit y t o calculat e despit e int act number reading
and in t he absence of spat ial def icit s, appears most of t en w it h bilat eral
hemispheric or dominant ret ro-Rolandic or basal ganglia lesions[84] . I solat ed
acalculia is most of t en associat ed w it h lesions of t he pariet ot emporal region
in t he dominant hemisphere but may also occur w it h medial f ront al cort ical
lesions and in subcort ical lesions involving t he caudat e nucleus, put amen,
and int ernal capsule[261] . I mpairment of analyt ic memory and at t ent ion plays
a role in many of t hese cases. Mult iplicat ion and division are usually most
impaired. Diff erent processing syst ems are responsible f or each of t he basic
arit hmet ic operat ions[261] . For example, a pat ient w it h a lef t
pariet ot emporal hemorrhage had select ive acalculia f or addit ion,
mult iplicat ion, and division but an int act abilit y t o subt ract [261] .
Primary dyscalculia has been described w it h inf arct ion in t he t errit ory of t he lef t
ant erior cerebral art ery t hat dest royed t he medial cort ex of t he f ront al lobe[289] .
Lexical and synt act ic processing of verbal and Arabic numbers and
comprehension of operat ion symbols w ere int act , but ret rieval of basic,
overlearned f act s w as mildly impaired, and execut ion of calculat ion procedures
w as more severely impaired. The locat ion of t he lesion suggest ed part icipat ion
of medial f ront al areas in
calculat ion processes[289] . Acalculia f rom def ect s of numeric synt ax, loss of
abilit y t o manipulat e mat hemat ic concept s, and impaired w orking memory may
also occur w it h subcort ical lesions of t he dominant hemisphere (e. g. , an inf arct
involving t he lef t caudat e, ant erior–superior put amen, and ant erior limb of t he
int ernal capsule ext ending superiorly int o t he perivent ricular w hit e mat t er)[ 84] .
Disturbances of Sensorimotor Integration and of

Movement Execution (Parietal, Frontal)
Apraxias
Parietal Apraxia
Apraxia has been def ined as a disorder of skilled movement t hat is not caused
by w eakness, sensory loss, abnormalit y of t one or post ure, abnormal
movement s, int ellect ual det eriorat ion, or poor comprehension [157, 251, 274] .
This def icit becomes most obvious w hen t he pat ient is asked t o perf orm a
pant omime, such as t o make believe he is light ing a cigaret t e or combing his
hair. Pat ient s w it h dominant -hemisphere lesions in t he neighborhood of t he
int rapariet al sulcus (inf erior pariet al lobe) become bef uddled or perf orm t he
w rong sequence of movement s on command. For movement s such as t he ones
ment ioned in t he preceding t ext , w hich require t he use of t he hand, t hey of t en
use t he hand as an object (e. g. , as a comb). How ever, t hey perf orm bet t er or
normally w it h init iat ion or w hen given t he act ual object . This t ype of apraxia,
w hich has been t ermed i deomotor apraxi a[ 210] , also appears w it h lesions of t he
premot or area of t he f ront al lobe (Brodmann's areas 6 and 8). Clinically, t hese
t w o locat ions of apraxia can be dist inguished because pariet al apraxia is
accompanied by a great er degree of diff icult y in recognizing t hat a mot or
perf ormance (by t he pat ient or ot hers) w as poor[207] . Tradit ionally, it has been
t hought t hat , just as one hemisphere is dominant f or language, t he ot her is
dominant f or t he perf ormance of movement f ormulas and “object -f ree” mot or
act s. I n right -handed individuals, t he lef t hemisphere w ould be dominant f or
praxis and speech[17] . I n lef t -handers, t hese f unct ions may be represent ed in
t he opposit e hemisphere. Theref ore, af t er a high pariet al lesion on t he right
hemisphere, a lef t -handed man developed apraxia w it hout aphasia, but t his w as
accompanied by an inabilit y t o discriminat e w ell-perf ormed f rom poorly
perf ormed act s[207] .
FI G URE 20-16 Anat omic diagram depict ing t he recept ion and decoding of a
mot or command in Wernicke's area (1), t ransmission of t he inf ormat ion
t hrough t he arcuat e f asciculus (2) t o t he lef t premot or area (3), and
subsequent t ransmission of t he inf ormat ion across t he corpus callosum (5) t o
t he right premot or area (6). Apraxic syndromes may occur w it h lesions along
t hese pat hw ays (see t ext ). Number 4 = lef t mot or cort ex; 7 = right mot or
cort ex.
The diagnosis of ideomot or apraxia requires t hat t he pat ient cannot carry out a
mot or command, can be show n t o underst and t he command, and can perf orm t he
same mot or act in a diff erent cont ext [157, 251] . The classic t eaching about
ideomot or apraxia w as summarized by G eschw ind in 1975 (Fig. 20-16) [1, 6,
173, 251] . I n t his scheme,
t he command must f irst be heard and t hen decoded int o language and processed
in t he appropriat e post erior brain region, part icularly Wernicke's area f or verbal
commands. The post erior region t hen act ivat es t he mot or associat ion cort ex (t he
premot or area) f or t he required body part t hrough w hit e mat t er connect ions
(t ypically represent ed as t he arcuat e f asciculus) running f rom t emporopariet al
regions t o t he midf ront al region. The lef t premot or area is considered dominant
f or learned mot or act s. I f t he desired act ion involves t he right ext remit ies, t he
lef t premot or area act ivat es t he appropriat e mot or neurons in t he lef t mot or
cort ex; if t he act involves t he lef t arm and leg, t he inf ormat ion is t ransmit t ed
f rom t he lef t premot or area t o t he right premot or area (and t hen t o t he right
mot or cort ex) t hrough t he corpus callosum.
According t o G eschw ind's scheme, a lesion of t he lef t superior t emporal area
causes a Wernicke's aphasia; because t he pat ient cannot underst and t he
command t o act , he/ she is not apraxic. How ever, some pat ient s w it h adequat e
underst anding of commands may also have apraxia due t o t he f ailure of mot or
inf ormat ion t o be t ransmit t ed t o t he lef t pref ront al area f or execut ion. Apraxia in
t hese pat ient s aff ect s bot h sides of t he body and also aff ect s buccof acial
movement s (buccof aci al apraxi a). Lesions of t he w hit e mat t er connect ions
(arcuat e f asciculus), usually in t he pariet al lobe, may cause a conduct ive aphasia
of t en associat ed w it h a right hemiparesis. These pat ient s underst and mot or
commands and, t heref ore, apraxia may be evident in t he nonparalyzed lef t
ext remit ies and buccof acial musculat ure. Lesions of t he lef t premot or cort ex
cause a Broca's aphasia associat ed w it h a right hemiparesis; lef t -limb
clumsiness and apraxia may occur, ref lect ing t he inabilit y of t he dominant
premot or cort ex t o program t he int act right -hemisphere mot or cort ex. Lesions of
t he ant erior corpus callosum, or deep f ront al w hit e mat t er on eit her side of t he
corpus callosum, disconnect t he lef t premot or cort ex f rom t he right premot or
cort ex. Theref ore, callosal apraxia result s; t here is select ive apraxia of lef t limb
movement s, and t he pat ient is able t o move t he right limbs normally in response
t o commands[251] .
I n pat ient s w it h t herapeut ic callosot omies (sect ion of t he corpus callosum), t he
right hemisphere can organize relat ively simple sequences of lef t -handed
movement s w it hout t he part icipat ion of t he lef t hemisphere[471] . I t can probably
also organize object -f ree movement s, because callosal sect ion does not induce
apraxia. Apraxia of t he lef t hand has been report ed in clinical cases in w hich t he
corpus callosum had been involved by ischemia or t umors (callosal apraxia).
These cases, are how ever, compounded by damage t o t he mesial aspect of t he
f ront al lobe t hat by it self may int erf ere w it h t he perf ormance of bimanual
coordinat ion t asks[57, 180] .
Theref ore, lef t f ront al lesions produce buccof acial apraxia, right hemiparesis,
and lef t limb apraxia, and lef t pariet al lesions produce buccof acial apraxia and
bilat eral limb apraxia[5] . A st udy by Alexander, Baker, Naeser, and ot hers
reexamined t he G eschw ind f ormulat ion f or limb ideomot or apraxia[5] . I n t his
st udy, buccof acial and respirat ory ideomot or apraxia had a high correlat ion w it h
lesions simult aneously occurring in t he f ront al operculum and t he ant erior
paravent ricular w hit e mat t er. No specif ic lesion sit e correlat ed w it h limb apraxia,
how ever, and all t hat could be concluded w as t hat damage t o a w ide area of t he
lef t hemisphere could produce limb ideomot or apraxia. Large lef t hemisphere
cort icosubcort ical lesions in t he suprasylvian peri-Rolandic region are part icularly
likely t o cause limb ideomot or apraxia; small lesions t hat cause limb ideomot or
apraxia are usually in t he pariet al w hit e mat t er or in t he cent ral paravent ricular
w hit e mat t er. These aut hors suggest t hat t he neural net w ork f or limb ideomot or
apraxia seems t o include bot h post erior regions (perhaps in large regions of
inf erior and superior pariet al lobules) and a long series of int rahemispheric
connect ions t o more ant erior eff ect or syst ems. This t opographically diff use
syst em of organizat ion and connect ion may account f or t he high f requency of
limb ideomot or apraxia w it h suprasylvian and deep lesions t hat also cause
aphasia[ 5] . O t her aut hors have conf irmed an aphasia/ apraxia double dissociat ion
(i. e. , some pat ient s may have apraxia w it hout aphasia and ot hers may have
aphasia w it hout apraxia), suggest ing t hat praxis and language make use of t w o
diff erent , part ly overlapping net w orks[355] . Aphasia occurs more of t en w it h
perisylvian lesions, aff ect ing associat ion areas f or t he f ace, w hereas limb
apraxia occurs w it h higher lat eral hemispheric lesions, in associat ion areas f or
t he hand[207] .
Pat ient s w it h bilat eral lesions in t he neighborhood of t he int rapariet al sulcus have
t he great est diff icult y in perf orming object -f ree movement s and of t en exhibit
impairment of more element ary movement s as w ell. They may miscalculat e
reaching f or a f ork under visual guidance or using it t o bring f ood t o t he mout h.
Proximal, less elaborat e movement s, like ambulat ion, are unimpaired. This
port ion of t he pariet al lobe is import ant f or t he learning of mot or pat t erns, t o a
great ext ent by imit at ion[385] . Corresponding areas in monkeys have been
show n t o cont ain populat ions of “mirror-neurons, ” w hich discharge specif ically
w hen t he animal observes t he perf ormance of a given mot or pat t ern[385] .
Apraxia is a prominent f eat ure of some progressive movement disorders,

part icularly cort icobasal degenerat ion[493] . I t is also f ound in ot her
neurodegenerat ive disorders, such as primary progressive apraxia, of t en w it h
Pick's complex pat hology, and progressive supranuclear palsy.
Dressi ng and constructi onal apraxi a are discussed in t his chapt er among t he
disorders of spat ial relat ionships.
Anterior (Frontal) Apraxias

We have considered t he impairment of mot or perf ormance derived f rom pariet al
or premot or lesions (ideomot or apraxia). Unilat eral lesions of t he SMA impair t he
perf ormance of t asks in w hich bimanual coordinat ion is required[57] . Pat ient s
w it h SMA lesions due t o lef t mesial hemisphere inf arct ion may have bilat eral
f ailure of sequence of movement s (ideomot or apraxia or apraxia f or sequent ial
act s) f or t ransit ive limb movement s, suggest ing t hat t he t ypes of skilled mot or
act s programmed by t he lef t SMA are learned t ransit ive limb movement s[251] .
Unlike many pat ient s w it h pariet al lesions, t hese pat ient s may bot h comprehend
and discriminat e pant omimes. Also, t asks of reciprocal coordinat ion are
impaired, such as repet it ively making a f ist w it h one hand w hen opening t he
ot her. This is also ref lect ed by an inabilit y t o draw alt ernat ing pat t erns and by
const ruct ional perseverat ion (Fig. 20-17). Writ ing is of t en impaired, more so w it h
lesions of t he lef t hemisphere[8, 303] . The hand cont ralat eral t o t he lesion has a
t endency t o grasp w hen t he palm is st imulat ed (grasp ref lex) and may perf orm
seemingly purposef ul movement s (such as reaching f or an object or imit at ing
w hat t he ot her hand is doing) t hat are unw illed by t he pat ient (al i en hand si gn)
[ 180] .
FI G URE 20-17 A: Perseverat ion is evident in t his copying t ask by a 76-year-

old w oman w it h a recent inf arct in t he dist ribut ion of t he lef t ant erior
cerebral art ery (B). (Reprint ed w it h permission f rom Masdeu JC, Schoene
WC, Funkenst ein H. Aphasia f ollow ing inf arct ion of t he lef t supplement ary
mot or area: a clinicopat hologic st udy. Neurol ogy. 1978; 28: 1220–1223).
The al i en l i mb si gn includes f ailure t o recognize ow nership of one's limb w hen

visual cues are removed, a f eeling t hat one body part is f oreign, personif icat ion
of t he aff ect ed body part , and aut onomous act ivit y t hat is perceived as out side
volunt ary cont rol[127] . Alt hough t he hand is most f requent ly aff ect ed, any limb or
combinat ion of limbs may f ulf ill t he alien limb crit eria. I n a st udy of seven
pat ient s w it h t he alien hand sign, et iologies included mult iple inf arct s and
cort icobasal ganglionic degenerat ion[127] . All pat ient s in t his st udy had apraxia
in response t o verbal commands and problems w it h bimanual coordinat ion; most
displayed non-goal-direct ed involunt ary mot or act ivit ies, and t w o had self -
dest ruct ive mot or behaviors. Cort ical ref lex myoclonus w as f requent ly present .
Lesions included sect ion of t he corpus callosum, mesial f ront al lesions, and a
combinat ion of post erior corpus callosum inf arct ion w it h a t halamic inf arct [127] .
O t her causes of t he alien hand syndrome include Alzheimer's disease,
cont ralat eral f ront al st rokes, corpus callosum inf arct ion, ant erior communicat ing
art ery rupt ure, corpus callosect omy, corpus callosum t umors, bif ront al
penet rat ing cerebral injury, and combined post erior corpus callosum and
cont ralat eral t halamic lesions [22, 23, 127, 174, 180, 282, 317] .
Tw o dist inct alien hand syndromes have been described[141] . The f rontal alien
hand syndrome occurs in t he dominant hand; is associat ed w it h ref lexive
grasping, groping, and compulsive manipulat ion of t ools; and result s f rom
damage t o t he SMA, ant erior cingulat e gyrus, and medial pref ront al cort ex of t he
dominant hemisphere and ant erior corpus callosum. I t is explained by an
increased t endency f or dominant limb explorat ory
ref lexes coupled w it h release f rom an asymmet rically dist ribut ed, predominant
nondominant hemisphere inhibit ion. Cal l osal alien hand syndrome is
charact erized primarily by int ermanual conf lict and, in t heory, requires only an
ant erior callosal lesion. I t is explained by hemispheric disconnect ion manif est ed
during behaviors requiring dominant hemisphere cont rol[141] . How ever, in many
cases of a “callosal” alien hand, t he SMA has been involved in addit ion t o t he
corpus callosus in chronic f orms of t he alien hand syndrome aff ect ing t he lef t
nondominant hand[459] .
A paroxysmal f orm of t he alien hand syndrome, probably due t o ict al
mechanisms, has also been described[276] . Tw o pat ient s w it h damage t o one
f ront omedial cort ex had brief episodes of abnormal mot or behavior of t he
cont ralat eral arm t hat f eat ured groping, grasping, and apparent ly purposef ul but
perseverat ive movement s t hat bot h pat ient s int erpret ed as alien or f oreign. Tw o
ot her pat ient s w it h post erior pariet al damage report ed a paroxysmal f eeling of
unaw areness of t he locat ion of t he cont ralat eral arm, lack of recognit ion of t he
arm as t heir ow n, purposeless movement s, and personif icat ion of t he arm[276] .
A pat ient w it h similar f indings f rom a post erior cerebral art ery inf arct ion has
been described as having a “sensory alien hand”[18] .
Pat ient s w it h f ront al lobe lesions, especially lesions aff ect ing t he inf erior half of
t he ant erior part of one or bot h f ront al lobes, may demonst rat e i mi tati on
behavi or and uti l i zati on behavi or[ 285] . Wit h imit at ion behavior t he pat ient
imit at es t he examiner's gest ures alt hough not inst ruct ed t o do so, t hinking t hat
he “had t o imit at e” t he examiner. Ut ilizat ion behavior is a dist urbance in response
t o ext ernal st imuli in w hich t he sight of an object implies an “order t o use it . ”
These behaviors are int erpret ed as release of pariet al lobe act ivit ies result ing
f rom impaired f ront al lobe inhibit ion[285] and are part of t he envi ronmental
dependency syndrome, w hich is a disorder of personal aut onomy in w hich t he
pat ient 's act ivit ies are excessively dependent on environment al cues[284] (e. g. ,
w hen t he pat ient sees a bed, she undresses and get s int o it ).
Lesions in t he pat hw ays originat ing in t he mesial f ront al cort ex are of t en
accompanied by a charact erist ic gait (apraxia of gait ). The pat ient appears t o be
st uck t o t he f loor (magnet ic gait ) and has diff icult y lif t ing up each f oot t o t ake
t he next st ep[328] . As a result , t he f eet drag along, and st eps are short . Turns
are part icularly diff icult . The result ant gait t heref ore resembles t hat of pat ient s
w it h Parkinson's disease, due t o bilat eral nigral degenerat ion. Pat ient s w it h
f ront al apraxia of gait due t o mesial f ront al disease perf orm clumsily w hen asked
t o kick an imaginary ball or t o out line a circle w it h t he f oot . These movement s
are perf ormed slow ly but correct ly by pat ient s w it h t he most common causes of
apraxia of gait : bilat eral subcort ical inf arct s in t he paracent ral w hit e mat t er of
t he cent rum semiovale and st ret ching by hydrocephalus of t he f ibers project ing
f rom t he mesial aspect of t he f ront al lobe as t hey sw eep around t he vent ricles.
Seizures originat ing in t he SMA induce head t urning t o t he opposit e side and
raising of t he cont ralat eral hand t o t he level of t he head, in such a w ay t hat t he
pat ient seems t o be perf orming a milit ary salut e (“salut at ory” seizures).
Lesions of t he mesial aspect of t he f ront al lobe cause akinesia (paucit y of
movement ). The cont ralat eral limbs are used sparingly, alt hough w hen used t hey
appear st rong. Bilat eral lesions cause paucit y of movement and of speech
(akinet ic mut ism)[ 238, 303] . Some pat ient s w it h bilat eral mesial f ront al lesions
(and perhaps also t hose w it h bilat eral pallidal pat hology) have a remarkable
disorder of movement . They can be f ully orient ed and move t he limbs w ell on
command, yet t hey do not use t hem t o t ake care of t heir needs. Such a pat ient
request ed w at er but did not even at t empt t o reach f or t he cup off ered him,
alt hough he could raise eit her arm on command. This disorder cont rast s w it h
most of t he apraxias described in t he preceding t ext , in w hich object -bound
act ions are generally perf ormed bet t er and more easily t han object -f ree act ions
(e. g. , a pant omime on command). These pat ient s also f ail t o perf orm movement s
t hat require a pref erent ial use of t he axial muscles, such as pushing t hemselves
up in bed, shif t ing posit ion, or get t ing up. This abnormalit y of movement may be
a minor degree of t he syndrome described in t he preceding t ext above as
akinet ic mut ism, usually present w it h large bilat eral lesions in t he medial f ront al
or medial t halamodiencephalic regions.
Lesions in t he peri-Rolandic cort ex cause impairment of f ine dist al movement s of
t he cont ralat eral hand. Picking up small object s by apposing t he index f inger and
t humb or handling a small coin may become impossible. This t ype of apraxia has
been t ermed l i mb-ki neti c apraxi a[ 157, 251] . Because separat e f ine movement s
of each f inger are unavailable, t hese pat ient s pick up a pen or a coin by pressing
it against t he palm w it h t he proximal port ion of t he t humb, much as inf ant s do
bef ore t hey develop pincer grip.
I n t he absence of isomet ric w eakness, t ransient unst eadiness of t he proximal
muscles of t he aff ect ed arm during t he f inger-nose t est has been described w it h
small inf arct s in t he hand area of t he precent ral gyrus[349] . Alt hough t he
movement w as not f urt her charact erized, oscillat ions of t he proximal muscles
w ere described[349] .
Pat ient s w it h dominant inf erior f ront al lesions may demonst rat e apraxi a of
speech. The hallmark of t his condit ion is t hat aut omat ic or react ive speech is
spoken w it hout errors, but volit ional or purposive speech cont ains subst it ut ions,
addit ions, repet it ions, prolongat ions, and reversal of phonemes[108] . These
pat ient s demonst rat e visible and audible groping f or correct art iculat ory post ures
and have slow prosody, w it h all syllables receiving equal st ress. As art iculat ory
complexit y increases (e. g. , consonant clust ers and mult isyllabic w ords), t here
are more errors, w it h perseverat ion occasionally evident .
Other M otor Disturbances of the Extremities or Face

“Pyramidal” Weakness
Lesions of t he mot or st rip or f ibers t heref rom induce impairment in t he volunt ary
cont rol of t he limb represent ed in t he aff ect ed port ion of t he cort ex[290, 448]
(Fig. 20-6). Somet ime af t er t he lesion occurs, spast icit y develops in t he aff ect ed
limb. Brisk muscle st ret ch ref lexes usually precede t he onset of spast icit y.
Clumsiness in t he use of t he arm is discussed in t he preceding t ext . Lesions of
t he medial aspect of t he f ront al lobe in t he area of represent at ion of t he legs
(paracent ral lobule) give rise primarily t o w eakness of f oot dorsif lexion and of
alt ernat ing movement s of t he t oes. Weakness of t he oropharynx, lips, and t ongue
occur f rom lesions of t he low Rolandic region and insula; w eakness of t he f ace
f rom lesions of t he Rolandic cort ex just above; w eakness of t he arm, hand, and
f ingers f rom even higher lesions; w eakness of t he leg and f oot f rom lesions of
t he Rolandic region f acing t he int erhemispheric f issure; and w eakness of t he
shoulder and hip f rom lesions of t he mot or areas just ant erior t o t he Rolandic
regions. Neuroimaging t echniques have conf irmed t he t radit ional represent at ion
of t he mot or homunculus described by Penf ield[28, 362] . A Babinski's sign and, if
t he lesion involves t he mesial aspect of t he f irst f ront al gyrus, a grasp response
may be present . Such lesions of t en aff ect bot h hemispheres, causing urinary
incont inence w it h uninhibit ed empt ying of t he bladder.
Lesions in t he int ernal capsule are of t en vascular and t end t o spare a
parat halamic rim of t he capsule w here t he sensory t ract s are locat ed. As a
result , t hey of t en cause “pure” mot or syndromes[12] . At superior levels of t he
int ernal capsule, t he f ace and bulbar muscles are most aff ect ed w it h lesions in
t he genu or ant erior part of t he post erior limb, w hereas more post eriorly locat ed
lesions cause arm w eakness, and t hose in t he most post erior part of t he
post erior limb give rise t o leg w eakness and visual f ield def ect s. More inf eriorly
in t he capsule, as it approaches t he midbrain, t he f ibers migrat e post eriorly and
a lesion in t he post erior limb can aff ect f ace, arm, and leg[487] . Large capsular
lesions have w orse prognosis f or f unct ional recovery t han cort ical or corona
radiat a lesions of a similar size[427] .
Paratonia (Gegenhalten)
Parat onia (increased muscle t one) result s f rom rat her ext ensive bilat eral
dysf unct ion of t he mesial cort ex and superior convexit y of t he f ront al lobes
(premot or cort ex, area 6). When a pat ient w it h parat onia is asked t o relax a joint
(elbow, knee) so t hat t he examiner may move it f reely, t he involved muscles
t ense up inst ead, and t he pat ient appears t o t he examiner t o be t rying t o act ively
oppose any movement of t he joint by t he examiner. The t one of t he involved
muscles increases in proport ion t o t he speed and st rengt h w it h w hich t he
examiner t ries t o move t he joint .
“Primitive” Reflexes
G rasping anyt hing t hat st imulat es t he palm of t he hand or f oot , sucking t o lip or
f acial st imulat ion, and t he corneomandibular ref lex are responses, present during
inf ancy, t hat disappear during childhood and t end t o reappear w it h aging. They
can be elicit ed in hydranencephalic inf ant s lacking suprast riat al brain st ruct ures.
Theref ore, it is t hought t hat as t he inf ant cort ex mat ures and myelinat ion
proceeds, t hese primit ive signs are inhibit ed. Cort ical or subcort ical damage,
part icularly damage aff ect ing t he f ront al lobes, w ould release t hem. Some
“primit ive” ref lexes have lit t le value in neurologic localizat ion. Up t o 25% of
normal adult s have a palmoment al ref lex, w hich becomes a very common f inding
in normal elderly individuals[235] . The grasp and suck ref lexes are more specif ic
indicat ors of ext ensive f ront al lobe disease. The grasp and snout ref lexes of t en
accompany impaired perf ormance of cognit ive t est s[460] .
Grasp Reflex
The grasp ref lex is elicit ed by st roking light ly t he palm of t he pat ient 's hand w it h
t he radial aspect of t he index f inger and t hen rubbing t he palm and t he volar
aspect of t he f ingers w it h a gent le f orw ard mot ion. The pat ient 's f ingers hook
around t he hand of t he examiner w ho can t hen pull f rom t he f lexed f ingers of t he
pat ient , w ho is unable t o release t he grip (f orced grasping ref lex). For t he ref lex
t o be most reliable, t he pat ient should be t old not t o grab t he examiner's f ingers.
Pat ient s w it h mild loss of cort ical inhibit ion may be able t o release t he grip
volunt arily, part icularly at t he beginning of t he elicit ing maneuver, bef ore st rong
t ension on t he f inger f lexors is applied. Dist ract ing t he pat ient w it h a t ask, such
as giving his or her address, allow s t he ref lex t o reappear. Damage
t o t he cont ralat eral area 6, part icularly in t he mesial aspect of t he hemisphere,

account s f or t he release of t he grasp ref lex.
Palmomen tal Reflex

The palmoment al ref lex consist s of a brief cont ract ion of t he ipsilat eral ment alis
muscle w hen t he palm of t he hand is briskly st roked w it h a blunt object . When
pronounced, t his ref lex may indicat e damage t o t he cont ralat eral paracent ral
cort ex or t he f ibers f rom it and can be elicit ed by st roking t he arm or even t he
chest .
Su ckin g, Sn ou t, Rootin g Reflexes

When t apping on t he upper lip elicit s a pursing-pout ing movement of t he lips, t he
pat ient is said t o have a snout ref lex. Curving of t he lips around a round object
applied t o t hem represent s a suck ref lex, w hich w hen accent uat ed may be
expressed by a sucking posit ion of t he lips and t urning of t he mout h t ow ard a
round object t hat approaches t he pat ient 's mout h or gent ly st rokes her cheek
(root ing ref lex). The snout ref lex may ref lect impairment of t he cort icobulbar
project ion, w hereas t he suck ref lex correlat es bet t er w it h diff use f ront al
premot or disease.
Corn eoman dibu lar Reflex, Eye, Jaw Syn kin esis
A corneomandibular ref lex occurs w hen t he pat ient 's jaw deviat es t o t he side
opposit e a st imulat ed cornea. Eye–jaw synkinesis, w hich is f ound in many normal
individuals, consist s of an ipsilat eral movement of t he jaw w hen t he pat ient
volunt arily looks sidew ays.
Opercu lar Syn drome, Pseu dobu lbar Palsy

I n addit ion t o dysart hria (and aphasia w hen on t he dominant hemisphere), acut e
lesions of t he f ront opariet al operculum cause diff icult y in sw allow ing liquids
(dysphagia), w hich t end t o come back t hrough t he nose[62] . When t he lesions
involving t he operculum or cort icobulbar pat hw ays are bilat eral, dysphagia t ends
t o last longer and may be permanent . I n t hose cases, saliva accumulat es in t he
mout h, aspirat ion of f ood may cause repeat ed bout s of pneumonia, and t he
pat ient may be aphonic. This array of sympt oms resembles t he clinical pict ure
produced by t he involvement of t he bulbar muscles t hemselves or by t he
involvement of t he neuromuscular junct ion, peripheral nerve, or medullary
neurons. Theref ore it has been t ermed pseudobul bar pal sy because, unlike
act ual bulbar palsy, t he bulbar muscles t hemselves are not aff ect ed and lack
at rophy.
The anteri or opercul ar syndrome ( Foi x-Chavany-Mari e syndrome or t he
syndrome of f acio-pharyngo-glosso-mast icat ory diplegia w it h aut omat ic volunt ary
movement dissociat ion) is due t o bilat eral ant erior perisylvian lesions involving
t he primary mot or cort ex and pariet al opercula [294] . Pat ient s w it h t his
syndrome lose volunt ary cont rol of f acial, pharyngeal, lingual, mast icat ory, and
somet imes ocular muscles. Ref lexive and aut omat ic f unct ions of t hese muscles
are preserved. These pat ient s may blink, laugh, or yaw n spont aneously, but t hey
cannot close t heir eyes or open t heir mout hs on command. They do not have
emot ional labilit y (uninhibit ed laught er and crying). The gag ref lex is decreased,
and sw allow ing is severely impaired[294] . Most of t en t he syndrome is produced
by variant s of upper mot or neuron disorders but may be caused by vascular
lesions and by chronic herpes simplex encephalit is[403] . Pat ient s w it h t he
ant erior opercular syndrome may be dist inguished f rom pat ient s w it h Broca's
aphasia, oral-buccal apraxia, pseudobulbar palsy, or bulbar palsy[39, 294] .
O cular mot or dist urbances relat ed t o f ront al or pariet al lesions are discussed in
Chapt er 8.
M otor Disturbances of Symbolic Behavior

Motor (Frontoparietal) Aphasias
Lesions involving t he ant erior port ion of t he f ront opariet al operculum cause
language dist urbances in w hich product ion of language is alt ered and reduced
(nonf luent aphasia), but comprehension of spoken language is preserved. As in
t he post erior (sensory) aphasias, t he degree and qualit y of language impairment
in ant erior aphasias depends on several f act ors. First , it depends on t he cort ical
represent at ion of mot or sequences (f ront al associat ion cort ex) and of t he
int egrat ion of kinest het ic and mot or inf ormat ion (pariet al associat ion cort ex) t hat
mediat e speech product ion. Uni l ateral lesions of t he “f ace area” of t he
precent ral gyrus (area 4; Fig. 20-6) cause t ransient dysart hria[247, 461] . The
verbal ut t erances cont ain a correct set of w ords, disposed in a grammat ically
correct order (phonemic and morphosynt act ic levels), yet t he art iculat ion of each
sound by t he oral muscles is clumsy. The pat ient speaks slow ly and eff ort f ully.
Because of oral muscle incoordinat ion, voiced consonant s such as b become
t heir devoiced count erpart s (b ri ghtarrow p), occlusive consonant s are
abnormally st rong, and f ricat ive consonant s adopt t he relat ed occlusive sound
(e. g. , z → d). Vow els are abnormally long and hesit ant , sounding like
pseudodipht hongs. As a result , t he pat ient 's speech resembles t hat of someone
w it h a f oreign accent [268] . Lesions of t he precent ral gyrus or f ibers t heref rom
cause cont ralat eral f acial w eakness involving t he low er f acial muscles, w hich is
most not iceable w hen t he pat ient speaks; t he aff ect ed orbicularis oris t hen
show s reduced speed and range of movement s. Bi l ateral lesions of t he
cort icobulbar f ibers originat ing in t he f ace region of area 4 cause last ing
dysart hria, w hich
may be severe (pure anarthri a or phoneti c di si ntegrati on syndrome, aphemi a).

Aphemia (usually t ransit ory) may result f rom small lesions of Broca's area or it s
subcort ical w hit e mat t er[405] . Such a syndrome is most of t en caused by bilat eral
inf arct s in t he cort icobulbar f ibers as t hey course in t he ant erior port ion of t he
post erior limb of t he int ernal capsule. This explains w hy t his dist urbance of
speech w as t ermed subcorti cal motor aphasi a. How ever, t hese pat ient s, even
w hen mut e, can w rit e correct ly and have no diff icult y in t he product ion of verbal
sequences as long as t hey do not have t o art iculat e t hem[268] . Aphemia may be
t he sole manif est at ion of primary progressive aphasia[80] .
FI G URE 20-18 A: Writ ing sample of a 43-year-old man w it h an embolic

inf arct of a cort ical st rip (Broca's and Exner's areas) ant erior t o t he primary
mot or cort ex f or t he mout h and hand. B: O ut line of t he inf arct area.
(Reprint ed w it h permission f rom Masdeu JC, O 'Hara RJ. Mot or aphasia
unaccompanied by f aciobrachial w eakness. Neurol ogy. 1983; 33: 519–521).
By cont rast , unilat eral lef t -sided lesions in t he st rip of cort ex immediat ely
ant erior t o t he primary mot or cort ex f or t he f ace, t hat is, t he cort ex in t he
post erior port ion of t he inf erior (and middle?) f ront al gyri (Broca's area) [96,
250, 333] , cause a t rue language dist urbance. Pat ient s w it h t rue Broca's aphasia
usually have ext ensive damage involving not only Broca's area (t he inf erior lef t
f ront al gyrus, w hich cont ains areas 44 and 45) but also t he surrounding f ront al
f ields (t he ext ernal aspect s of area 6 and areas 8, 9, 10, and 46) and t he
underlying w hit e mat t er and basal ganglia[96] . Alt hough t he pat ient know s w hat
he or she w ant s t o say and can recognize an appropriat e sent ence, he or she
cannot produce t he appropriat e sounds or w rit e a meaningf ul sequence of
let t ers[ 213, 302] . There is a drast ic loss of speech f luency, w it h speech
becoming eff ort f ul and of t en slow, w it h pauses bet w een w ords of t en
out numbering t he w ords t hemselves[96] . Speech and w rit ing are impaired t o t he
point of mut ism and complet e agraphia, in w hich t he pat ient can copy but cannot
w rit e spont aneously or on dict at ion (Fig. 20-18). Repet it ion is also impaired, but
w it h smaller lesions or w hen t he pat ient begins t o improve, repet it ion is usually
bet t er t han spont aneous speech. The speech of t hese pat ient s has an
agrammat ic charact er; f unct ion w ords, such as art icles, are omit t ed, and verbal
endings are dropped. Nouns f are bet t er t han verbs or adject ives, adverbs, and
ot her “f iller” w ords. Theref ore, t hese pat ient s convey much inf ormat ion using f ew
w ords (t elegraphic speech). Sound subst it ut ion, usually by including a st ressed
syllable of a w ord t hat comes lat er in t he sent ence, gives rise t o lit eral and
phonemic paraphasias. These are recognized by t he pat ient as paraphasic
errors, unlike t he sit uat ion t hat occurs w hen paraphasias are ut t ered as a result
of post erior lesions. Naming of object s is also impaired, but , unlike pat ient s w it h
t emporal lobe lesions, t hese pat ient s benef it f rom cueing. This cueing may be
phonet ic (e. g. , t he examiner mout hs t he beginning sound of t he w ord) or
cont ext ual (e. g. , “you pound a nail w it h a…”). Pat ient s w it h Broca's aphasia are
of t en depressed because of t heir plight and f rust rat ed by specif ic f ailures at
communicat ion[ 96] .
Last ing aphasia of t he t ype described in t he preceding t ext , w it h pronounced
agrammat ism and markedly reduced f luency (Broca's aphasi a), corresponds t o
lesions ext ending across t he f ront opariet al operculum, including t he post cent ral
and supramarginal gyri[7] . Pat ient s w it h t his t ype of Broca's aphasia have
diff icult y underst anding sent ences w hose meaning depends on synt ax (e. g. , “t he
boy w as kicked by t he cow ” vs. “t he boy kicked t he cow ”). This impairment may
be relat ed t o damage t o t he supramarginal gyrus, w hich is part of t he audit ory
associat ion cort ex[392] .
How ever, cort ical st imulat ion st udies suggest a more crit ical part icipat ion of t he
mot or sequencing areas of t he f ront opariet al perisylvian operculum in t he
decoding of t he phonemes t hat const it ut e t he synt act ic changes. The product ion
of verbs act ivat es select ively Broca's area and lesions here may impair some of
t he semant ic aspect s of verb product ion[363, 455] .
When damage is rest rict ed t o Broca's area alone or t o it s subjacent w hit e
mat t er, t rue Broca's aphasia does not develop[96] . I nst ead, t here is a mild and
t ransient aphasia ref erred t o as Broca's area aphasia[334] . This t ransient
aphasia, except f or decreased spont aneit y of t he pat ient 's speech (t ranscort ical
mot or aphasia), clears complet ely in t he course of a f ew days or w eeks[334] .
The st ruct ures usually damaged in Broca's aphasia are part of a neural net w ork
involved in t he assembly of bot h phonemes int o w ords and w ords int o sent ences,
t hat is, t he ordering of linguist ic component s in t ime and space[96] . This net w ork
is probably concerned w it h t he relat ional aspect s of language, w hich include t he
grammat ical st ruct ure of sent ences and t he proper use of grammat ical
morphemes and verbs; t he ot her cort ical component s of t his net w ork include t he
lat eral lef t f ront al cort ices (areas 47, 46, and 9), t he int erconnect ed lef t pariet al
cort ices (areas 40, 39, and 7), and t he sensorimot or cort ices above t he Sylvian
f issure bet w een Broca's and Wernicke's areas (t he low er sect or of areas 1, 2,
3, and 4), w it h crit ical subcort ical component s in t he lef t basal ganglia (head of
t he caudat e nucleus and put amen)[ 96] .
Pat ient s w it h large perisylvian lesions are mut e or have a nonf luent , agrammat ic
speech accompanied by impaired comprehension and repet it ion (gl obal aphasi a).
This t ype of aphasia t heref ore combines f eat ures of Broca's and Wernicke's
aphasia. When caused by an ischemic event , as is most of t en t he case, t he
pat ient may be init ially mut e or only groan unint elligibly. Pat ient s w it h global
aphasia f requent ly have st ereot ypic ut t erances t hat perhaps originat e f rom a
right -hemisphere mechanism f or aut omat ic residual speech, especially speech
t riggered or inf luenced by emot ions (e. g. , explet ives). O t her aut omat ic-speech
rout ines, such as count ing or recit ing t he days of t he w eek, are of t en int act , as
is t he abilit y t o hum previously learned melodies and sing t heir lyrics[96] .
G lobal aphasia is usually accompanied by w eakness of t he right side of t he f ace
and right hemiplegia. The presence or absence of hemiplegia is an import ant
clue t o t he localizat ion of brain damage[96] . When hemiplegia is present (classic
global aphasia) t he damage has aff ect ed t he ant erior language area (as in
Broca's aphasia), t he ent ire basal ganglia region, t he insula and audit ory
cort ices (as in conduct ion aphasia), and t he post erior language region (as in
Wernicke's aphasia). Such damage is almost alw ays caused by a large inf arct in
t he dist ribut ion of t he middle cerebral art ery[96] . G lobal aphasia w it hout ot her
lat eralizing signs (i. e. , no hemiparesis or last ing mot or def ect s) may occur w it h a
single dominant t emporopariet al lesion[49] but more of t en occurs w it h t w o
discret e lesions in t he dominant hemisphere, one f ront al and one
t emporopariet al[ 456, 465] . The lat t er sit uat ion is usually due t o embolic
st roke[ 199, 465] but may occur w it h nonembolic et iologies (e. g. ,
int raparenchymal hemat oma and cerebral met ast ases) t hat spare a w ide area of
mot or, sensory, and language-relat ed st ruct ures[271, 469] .
Anot her group of globally aphasic pat ient s have dominant f ront al lobe damage
w it h ext ension int o t he insula and basal ganglia (t he t emporal and pariet al
regions are int act ). Most of t hese pat ient s gradually improve but are
compromised by residual Broca's aphasia[96] . Anot her subt ype of global aphasia
is charact erized by an ext reme loss of communicat ive abilit ies (verbal as w ell as
nonverbal); t hese pat ient s complet ely lose speech out put and are inaccessible t o
any kind of message, w het her given verbally or t hrough gest ures (t he aphasic
isolat e)[ 120] . The prognosis in t hese individuals is poor, and w hereas some
lesions aff ect Broca's and Wernicke's areas, t he locat ion of lesions in ot her
cases ranges f rom ant erior cort ical damage t o post erior cort ical damage t o deep
nuclei damage[120] .
Nonf luency in spont aneous speech w as st udied in pat ient s w hose severit y of
spont aneous speech ranged f rom cases w it h no speech or only verbal
st ereot ypies t o t hose w it h reduced, hesit ant , poorly art iculat ed, agrammat ic
speech (nonf luent Broca's aphasia)[ 344] . The degree of nonf luency increased
depending on t he ext ent of t he lesion responsible f or t he condit ion in t w o
combi ned subcort ical w hit e mat t er areas: t he medial subcallosal f asciculus
(locat ed in t he lat eral angle of t he f ront al horn) and t he perivent ricular w hit e
mat t er near t he body of t he lat eral vent ricle, deep t o t he low er mot or-sensory
cort ex area f or t he mout h. The medial subcallosal f asciculus cont ains f ibers f rom
t he cingulat e gyrus and SMA t hat course t o t he caudat e nucleus; lesions of t his
f asciculus may t heref ore impair init iat ion and preparat ion of speech movement s
and limbic aspect s of speech. The w hit e mat t er lesion deep t o t he mot or-sensory
cort ex area f or t he mout h likely impairs pat hw ays necessary f or mot or execut ion
and sensory f eedback of spont aneous speech[7, 344] .
I n most right -handed people, t he lef t hemisphere is dominant f or speech. O nly
lef t -hemisphere lesions
cause t he dist urbances of symbolic behavior out lined in t he preceding t ext .

Among lef t -handers, language dominance is less clear-cut t han among right -
handers[ 375] . Lef t -hemisphere lesions may leave oral language unalt ered,
w hereas w rit ing and reading may be severely impaired (Fig. 20-14).
Approximat ely 50% of lef t -handers develop a language def icit , of t en t ransient ,
af t er lesions of t he lef t hemisphere. Hemispheric dominance appears early in
lif e. Complet e t ransf er of language capabilit ies t o t he right hemisphere w hen t he
lef t hemisphere suff ers a lesion is unlikely t o occur in children older t han 6
years[ 490] .
Some st udies, but not ot hers, have f ound great er lat eralizat ion of synt act ic
abilit ies t o t he lef t hemisphere in men[164, 425] .
I n bilingual individuals t he cort ical represent at ion of bot h languages is ident ical if
t he languages w ere learned early in lif e[214, 249] , or if t he individuals are just
as f luent in bot h languages[231] . How ever, f or t hose w ho acquired a second
language af t er adolescence, t he cort ical represent at ion in Broca's area (but not
in Wernicke's) t ends t o be diff erent f or eit her language[249] . O t her st udies have
show n larger areas of cort ical act ivat ion w it h semant ic t asks w hen t he second
language is used[113] . Pref ront al, Broca's and supramarginal cort ex play an
import ant role in language sw it ching and lesions in t hese areas could impair t his
f unct ion [214, 373, 397] .
I n addit ion t o t he locat ion of t he lesion and t he pat t ern of cort ical represent at ion,
t he amount of t ime elapsed since acut e cerebral insult (usually inf arct ion or
t rauma) det ermines t he t ype of language dist urbance. The init ial diff icult y in
producing and underst anding language (global aphasia) of t en evolves int o
Broca's aphasia because comprehension of spoken language improves. Anomia
may remain as t he only language def icit in pat ient s w ho, mont hs previously had a
language def icit ranging f rom Broca's aphasia t o t ranscort ical sensory aphasia.
The f ront al cort ices locat ed on t he int ernal (mesial) cerebral surf ace of t he lef t
hemisphere (e. g. , t he SMA and t he ant erior cingulat e gyrus) also play a part in
t he init iat ion and maint enance of speech [8, 96, 105] . Damage t o t hese areas
does not cause aphasia direct ly but rat her causes diff icult y w it h init iat ing
movement (akinesia) and mut ism. Pat ient s w it h akinesia and mut ism f ail t o
communicat e bot h by w ord and by gest ure or f acial expression; t heir drive t o
communicat e is no longer present [96] .
Pat ient s w it h aphasia or w it h unilat eral or bilat eral hemispheric lesions may
demonst rat e acqui red stutteri ng, w hich is diff erent f rom development al st ut t ering
in t hat st ut t ering may occur w it h singing and is f requent ly evident t hroughout t he
sent ence, not just evident at t he beginning of a sent ence or phrase[212] .
Acquired st ut t ering may occur w it h st roke, cerebral t rauma, Alzheimer's disease,
renal dialysis, Parkinson's disease, and progressive supranuclear palsy[151] .
Transcortical Motor Aphasia

Similar t o Broca's aphasia in t he lack of verbal spont aneit y, t ranscort ical mot or
aphasia diff ers f rom Broca's in t hat t he pat ient can repeat correct ly, and may
even correct synt act ic errors in t he original sent ence[8, 303] . The verbal out put
may resemble Broca's aphasia speech, w it h a grammat ical, t elegraphic speech,
or on t he cont rary, f eat ure grammat ically correct ut t erances w it h a marked
t endency f or perseverat ion. St ut t ering and t he repet it ion of t he same syllable or
w ord are common. Lesions causing t ranscort ical mot or aphasia almost alw ays
occur in t he dominant f ront al lobe, posit ioned eit her ant erior or superior t o
Broca's area, or are in t he SMA [8, 303, 390] . Lef t t halamic lesions may cause a
similar syndrome[345, 348] . Et iologies include cerebral hemorrhage, ant erior
cerebral art ery dist ribut ion inf arct ion, and int ernal carot id occlusion w it h
inf arct ion in t he border zone bet w een t he ant erior and middle cerebral art eries,
t umor, and head t rauma.
Motor Aprosodia
Pat ient s w it h nondominant f ront al-pariet al lesions may be unable t o express
emot ional color in t heir speech and gest ures. This aprosodia may be considered
t he aff ect ive equivalent of mot or aphasias.
Pure Agraphia
Writ ing dist urbances of t en accompany language def icit s and have similar
charact erist ics. How ever, t he degree and t ype of impairment can diff er w idely
f rom t he pat ient 's perf ormance w it h oral mat erial. The ext reme case, in w hich
t he pat ient w rit es poorly, alt hough oral language, reading, and praxis are normal,
is t ermed pure agraphi a. I t has been relat ed t o aff ect ion of t he post erior part of
t he second f ront al gyrus (Exner's area) or of t he superior pariet al lobule[287] .
Lesions of t he nondominant hemisphere may cause let t er reduplicat ion, slant ed
lines, and crow ding of t he w ords t o t he right side of t he paper[296] .
Disturbances of Goal-Oriented Behavior (Executive

Function Loss)
Execut ive processes include (a) f ocusing at t ent ion on relevant inf ormat ion and
processes and inhibit ing irrelevant ones (“at t ent ion and inhibit ion”), (b)
scheduling processes in complex t asks, w hich requires t he sw it ching of f ocused
at t ent ion bet w een t asks (“t ask management ”), (c) planning a sequence
of subt asks t o accomplish some goal (“planning”), (d) updat ing and checking t he
cont ent s of w orking memory t o det ermine t he next st ep in a sequent ial t ask
(“monit oring”), and (e) coding represent at ions in w orking memory f or t ime and
place of appearance (“coding”). Tasks involving each of t hese execut ive
processes are know n t o be select ively impaired in pat ient s w it h pref ront al
damage[ 431] .
As t he f ront al lobe is heavily involved in execut ive f unct ions, an overview of t he
syndromes caused by f ront al lesions f ollow s. Four principal f rontal l obe
syndromes relat ed t o personalit y and behavioral abnormalit ies have been
charact erized [458] :
1. O rbi tof rontal syndrome (di si nhi bi ted). The orbit of ront al cort ex is int erlinked
w it h limbic and ret icular areas, is act ivat ed w it h t he emot ions of anger or
f ear, and some of it s neurons respond select ively t o adversive st imuli[102,
242] . Lesions of t his area lead t o disinhibit ion and changes of aff ect .
Behavior is impulsive (pseudopsychopat hic). O t her charact erist ics include an
inappropriat e jocular aff ect (w it zelsucht ), euphoria, emot ional labilit y, poor
judgment and insight , and dist ract ibilit y[222] .
2. Frontal convexi ty syndrome (apatheti c). The lat eral f ront al cort ex is closely
linked t o mot or st ruct ures, so lesions of t his area lead t o dist urbances of
movement and act ion w it h preservat ion of inert ia. Pat ient s are apat het ic,
w it h occasional burst s of angry or aggressive behavior. O t her charact erist ics
include indiff erence, psychomot or ret ardat ion, mot or perseverat ion and
impersist ence, loss of set , st imulus boundedness, discrepant mot or and
verbal behavior, mot or programming def icit s, poor w ord list generat ion, poor
abst ract ion and cat egorizat ion, and a segment ed approach t o visuospat ial
analysis.
3. Medi al f rontal syndrome (aki neti c). This syndrome is associat ed w it h
mut ism, gait dist urbances, and incont inence. Pat ient s demonst rat e a paucit y
of spont aneous movement and gest ure, sparse verbal out put (repet it ion may
be preserved), low er ext remit y w eakness and loss of sensat ion, and
incont inence.
4. Massi ve f rontal l obe l esi ons. An apat het ic-akinet ic-abulic syndrome may
occur in w hich t he pat ient lies around passively, unaroused and unable t o
complet e t asks or list en t o commands.
Pat ient s w it h bilat eral lesions aff ect ing t he ant erior (so-called pref ront al) port ion
of t he f ront al lobes and orbit of ront al cort ex (areas 9, 10, and 11) have impaired
abilit y t o plan t heir f ut ure. Even w hen t hey voice a desire t o pursue personal
endeavors, such as f inding a job, t hey f ail t o carry out t he st eps necessary t o
achieve t hem. When t he damage is rest rict ed t o t he f ront al lobes, t hese pat ient s
may be perf ect ly w ell orient ed and obt ain normal scores in t he ordinary bat t ery
of cognit ive t est s. How ever, t hey t end t o perf orm poorly on open-ended t asks,
such as naming it ems t hat begin w it h a part icular let t er. They t end t o manif est
perseverat ion and, w hen t he lesion is great er in t he dominant f ront al lobe, have
sparse language w it h verbal int rusions, w hich are segment s of speech w it h lit t le
or no relevance t o t he cont ext t hat have been picked up f rom ext ernal st imuli
(such as a sign) or f rom previous segment s of speech.
O t her manif est at ions of impaired goal-orient ed behavior are described in t he
preceding t ext in t he sect ion on f ront al apraxia. Pat ient s w it h ant erior f ront al
lesions may show i mi tati on behavi or and uti l i zati on behavi or as part of t he
envi ronmental dependency syndrome[ 285] . Lacking self -init iat ive, t he pat ient 's
act ivit ies are excessively dependent on environment al cues (e. g. , w hen t he
pat ient sees a bed, he or she undresses and get s int o it )[ 284] .
Ut ilizat ion behavior has been described in a pat ient w it h a localized inf erior
medial bif ront al lesion[422] . The pat ient picked up and used irrelevant object s
not only w hen t hey w ere placed direct ly in f ront of him (t he i nduced f orm of
ut ilizat ion behavior, discussed in t he preceding t ext ), but also w hen he had been
inst ruct ed t o carry out ot her t asks and his at t ent ion had not been direct ed t o t he
object s (t he i nci dental f orm of ut ilizat ion behavior). The behavior occurred most
f requent ly in t he brief int ervals bet w een t asks, and more of t en w hen audit ory-
verbal rat her t han visuomot or t asks w ere being perf ormed[422] . Front al lobe-like
ut ilizat ion behavior has also been described w it h paramedian t halamic inf arct ion,
suggest ing a t halamof ront al component t o environment al int eract ions t hat require
inhibit ion, self -monit oring, and cognit ive f lexibilit y[137] .
The medial f ront al cort ex plays a crucial role in init iat ion, mot ivat ion, and goal-
direct ed behaviors. I t f orms an import ant part of t he dorsal at t ent ional
st ream[ 86] . I n t he post erior port ion of t he superior f ront al gyrus, t he SMA and
t he pre-SMA area, rost ral t o t he SMA, coordinat e sensorimot or inf ormat ion in a
t emporal f ramew ork[90, 359] . Alt hough SMA is relat ed t o at t ent ion t o move, pre-
SMA is relat ed t o t he int ent ion t o move[267] . Bot h SMA and pre-SMA are
involved in t he percept ion of t he int ent ionalit y of t he ot her individual (“t heory of
mind”)[ 421] and in t he imit at ion and learning of mot or pat t erns[399, 497] . Below
t hese areas, t he cingulat e sulcus separat es t hem f rom t he ant erior cingulat e
cort ex. To some ext ent , all t hese areas f unct ionally overlap[421] .
The anteri or ci ngul ate cortex is part of a larger mat rix of st ruct ures (including
t he amygdala, periaqueduct al grey, vent ral st riat um, orbit of ront al cort ex, and
ant erior insular cort ex) t hat f orm t he rost ral limbic syst em, w hich assesses t he
mot ivat ional cont ent of int ernal and ext ernal st imuli and regulat es cont ext -
dependent behaviors[123] . The af f ecti ve di vi si on of t he ant erior cingulat e cort ex
modulat es aut onomic act ivit y and int ernal emot ional responses, w hereas t he
cogni ti on di vi si on is engaged in response select ion associat ed w it h skelet omot or
act ivit y and responses t o noxious st imuli. Excessive cingulat e act ivit y, in cases
w it h seizure act ivit y conf irmed in t he ant erior cingulat e cort ex, can impair
consciousness, alt er aff ect ive st at e and expression, and inf luence skelet omot or
and aut onomic act ivit y. Elevat ed ant erior cingulat e cort ex act ivit y may cont ribut e
t o t ics, obsessive-compulsive behaviors, and aberrant social behavior. Reduced
cingulat e act ivit y f ollow ing inf arct s, surgery, or chronic cocaine use can
cont ribut e t o behavioral disorders, including akinet ic mut ism, diminished self -
aw areness and depression, mot or neglect and impaired mot or init iat ion, reduced
responses t o pain, and aberrant social behavior[123, 241] . Surgical cingulot omy,
f or t he t reat ment of chronic int ract able pain, involves t he bilat eral placement of
approximat ely 5 mm lesions in t he w hit e mat t er of t he ant erior cingulat e region,
approximat ely 1. 5 cm rost ral t o t he ant erior ext ent of t he paracent ral lobule[82] .
Pat ient s undergoing t his procedure, w ho have been f ollow ed longit udinally,
illust rat e t he changing manif est at ions of lesions in t his region as t ime elapses
and compensat ory mechanisms f all in place[258, 332] . Acut ely af t er cingulot omy
t hey had mut ism, akinesis, blunt ed aff ect , let hargy, and apat hy. Despit e
improvement , a f ew mont hs lat er t here remained a syndrome of impaired
execut ive f unct ion and at t ent ion, charact erized by decreased int ent ion and
spont aneous response product ion, along w it h mild def icit s of f ocused and
sust ained at t ent ion. Pat ient s cont inued t o show perf ormance variabilit y, slow ed
processing, and vulnerabilit y t o int erf erence[82] .
Disturbances Related to Interhemispheric

Disconnection (Callosal Syndrome)
Nonsurgical lesions (t rauma, inf arct ion, t umor) t hat dest roy t he corpus callosum
usually involve t he medial aspect of t he f ront al, pariet al, or occipit al lobes.
Theref ore, it becomes diff icult t o separat e t he eff ect s of t he callosal lesion per
se and t he eff ect s of t he neighboring hemispheric damage. Know ledge of t he
def icit t hat f ollow s on cleaner callosal lesions derives mainly f rom t he st udy of
epilept ic pat ient s w ho underw ent sect ion of t he corpus callosum and ant erior
commissure in order t o reduce int erhemispheric propagat ion and kindling. The
int erhemispheric disconnect ion does not int erf ere w it h most act ivit ies of daily
living but becomes apparent in t he f ailure, by a lef t hemisphere–dominant
individual, t o perf orm t asks such as t he f ollow ing[111, 275] :
1. Naming an object brief ly present ed t o t he lef t hemif ield, alt hough t he same
can be chosen by t he lef t hand f rom an array of diff erent object s. Lack of
visual t ransf er may also be evident at t he bedside by t est ing t he visual f ields
w it h t he usual conf ront at ion met hod, w hich reveals a “double hemianopia. ”
The pat ient is asked t o point t o t he moving t arget f irst w it h his lef t hand
(w hen a right homonymous hemianopia is recorded) and t hen w it h his right
hand (w hich f ails t o point t o st imuli in t he lef t hemif ield).
2. Reading w ords brief ly present ed t o t he lef t hemif ield only (l ef t hemi al exi a)
[ 81] .
3. I mit at ing w it h one hand t he posit ion of t he cont ralat eral hand, w hich is kept
hidden f rom view.
4. Naming object s, kept f rom view, palpat ed by t he lef t hand (uni l ateral tacti l e
anomi a).
5. Writ ing w it h t he lef t hand (uni l ateral agraphi a) or perf orming w it h t he lef t -
hand commands t hat involve object less act ivit y, such as “Pret end t hat you
are t urning a knob. ” Apraxia of t he lef t body may be evident [190] . The lef t
hand may make more errors in mat ching-t o-sample t asks w hen it is not
possible t o see t he st imulus t hat is t o be mat ched[295] . A callosal lesion
caused lef t unilat eral ideomot or apraxia but w it hout lef t -sided agraphia,
suggest ing t hat t he callosal f ibers f or w rit ing cross more post eriorly t han
t hose f or praxis, w hich seem t o cross in t he more rost ral part of t he
post erior half of t he callosum[244] .
6. Copying a somew hat complex design w it h t he right hand, w hich is clearly
out done in t he same t ask by t he perf ormance of t he lef t hand (ri ght-hand
constructi onal apraxi a).
Lack of int ermanual coordinat ion and even a sit uat ion in w hich t he lef t hand act s
independent ly f rom t he pat ient 's volit ion (al i en hand si gn) may result f rom
combined callosal and mesial f ront al damage[23] , and seems t o correlat e w it h
damage of t he midport ion of t he corpus callosum[174] .
A diff erent perspect ive of t he “split -brain” syndrome w as proposed by
Sergent [ 417] , w ho considered t he “split brain” as a single organism and t he t w o
disconnect ed hemispheres as int egral component s of t his organism connect ed t o
one anot her by subcort ical st ruct ures. Tw o commissurot omized pat ient s w ere
present ed w it h simult aneous bilat eral
inf ormat ion such t hat neit her hemisphere received suff icient inf ormat ion t o make
a f inal decision. O nly by combining t he init ially segregat ed inf ormat ion could a
correct response be produced. Bot h pat ient s perf ormed signif icant ly above
chance on a number of t asks suggest ing t hat inf ormat ion divided bet w een t he
hemispheres could be unit ed, relat ed, and act ed on in a unif ied manner despit e
each hemisphere being unaw are of t he inf ormat ion received by t he ot her[417] .
Gait Disorders
Disease of t he f ront al lobes can cause gait disorders. These disorders and t heir
localizat ion are discussed in Chapt er 1.
Dementia
Dement ia has been def ined as a loss of int ellect ual abilit ies of suff icient severit y
t o int erf ere w it h social or occupat ional f unct ioning[10] . More relevant t o t he
scope of t his chapt er, dement ia ref ers t o det eriorat ion of ment al f unct ion due t o
diff use or disseminat ed disease of t he cerebral hemispheres [366] . Bilat eral
lesions of t he medial hypot halamus or t halamus, discussed in Chapt ers 17 and
18, may also cause severe memory loss and at t ent ional disorders result ing in
dement ia. A pat ient w it h bilat eral f ront al disease may have a rat her good
memory, and yet t he abilit y t o plan in t he f ut ure and t o st ick w it h a t ask is so
impaired t hat it int erf eres seriously w it h social or occupat ional f unct ioning. These
t w o inst ances exemplif y t he het erogeneit y of t he condit ions know n as dementi as
as f ar as cerebral localizat ion is concerned. The onset of dement ia can be
sudden, as w hen it f ollow s severe head t rauma, or insidious, as w it h Alzheimer's
disease. I n eit her case, t he pat ient w it h dement ia has a clinical present at ion t hat
corresponds t o bi l ateral , rat her ext ensive, damage of t he cerebral cort ex,
subcort ical st ruct ures, or, very of t en, bot h.
When t he lesions are predominant ly corti cal , t he clinical f indings depend on t he
part of t he cort ex t hat bears t he brunt of pat hology. Senile dement ia of t he
Alzheimer t ype (w hich account s f or about more t han half t he cases of slow ly
progressive dement ias) has an import ant subcort ical component but also t ends
t o aff ect roughly symmet ric areas of t he cort ex, result ing in a diff erent
t opographic predominance in diff erent pat ient s. The process spreads f rom t he
limbic cort ex t o t he associat ion areas of t he neocort ex[53, 305] . Because t he
medial aspect of t he t emporal lobes is involved early, memory loss is an early
f eat ure. I nvolvement of t he associat ion cort ex of t he t emporal and pariet al lobes
gives rise t o aphasias, visuospat ial def icit s, and apraxias[14] . I n dement ias
w here t he f ront al lobes are primarily aff ect ed (as in Pick's disease, in ot her
f ront ot emporal dement ias, and in some cases of Alzheimer's disease), t he
pat ient lacks drive, neglect s social nuances, and may have t he primit ive signs,
mot or aphasia, and ot her f ront al lobe f indings described in t he preceding t ext [15,
185] . Element ary mot or and sensory dist urbances, such as limb w eakness, never
occur unt il lat e in t he clinical course.
By cont rast , dement ias such as progressive supranuclear palsy or ot hers w it h
pref erent ial involvement of t he subcort ical nuclei cause abnormalit ies of
movement and overall slow ing of psychomot or f unct ion, w it h prominent
at t ent ional def icit s and f orget f ulness[467] . Speech may be dysart hric, but not
aphasic. I n subcort ical art eriosclerot ic encephalopat hy, t halamic damage may
cause memory loss[467] .
Depression and ot her psychiat ric disorders may mimic dement ia
(“pseudodement ia”). Because t heir t reat ment diff ers f rom t hat of dement ia, t his
dist inct ion is import ant . Some helpf ul diff erent ial f indings are list ed in Table 20-
4.
I n t he preceding pages, t he emphasis has been placed on t he symptoms and
si gns t hat result f rom hemispheric lesions. Table 20-5 list s t he regions of t he
cerebral hemispheres and t he clinical manif est at ions of lesions in each region.
TABLE 20-4 Clinical Features Differentiating Pseudo-

dementia From Dementia
Pseudo-dem entia Dem entia
Clinical course and history
Family aware of Family often unaware of

dysfunction degree of dysfunction
Insidious, onset can be

Onset can be dated with
dated only within broad
some precision
limits
Rapid progression of
Often slow progression
symptoms after onset
History of previous History of previous
psychiatric dysfunction psychiatric dysfunction
common unusual
Complaints and clinical behavior
Patients usually
Patients usually complain
complain much of
little of cognitive loss
cognitive loss
Patients emphasize
Patients conceal disability
disability
Patients make little

Some patients struggle to
effort to perform even
perform
simple tasks
Patients usually
Patients often appear
communicate strong
unconcerned
sense of distress
Affective change often

Affect labile and shallow
pervasive
Behavior often Behavior usually

incongruent with severity compatible with severity of
of cognitive dysfunction cognitive dysfunction
Nocturnal accentuation Nocturnal accentuation of

of dysfunction uncommon dysfunction common
“Don't know” answers “Near miss” answers

typical frequent
Memory loss for recent Memory loss for recent

and remote events equally events more severe than
severe for remote events
TABLE 20-5 Consequences of Localized Cerebral

Hemispheric Lesions
1. Occipital lobe
1. Mesial
1. Visual field defects
2. Visual agnosia
3. Visual hallucinations
4. Alexia without agraphia
5. Visual anosognosia; Anton syndrome (denial of
blindness)
2. Lateral
1. Alexia with agraphia
2. Impaired opticokinetic nystagmus
3. Impaired ipsilateral scanning
4. Palinopsia
5. Visual allesthesia
2. Temporal Lobe
1. Inferomedial aspect (amygdala and hippocampus)
1. Amnesia (impaired storage)
1. Greater for verbal information with left
involvement
2. Greater for visuospatial material with right
involvement
2. Anterior tip (bilateral lesions)
1. Kluver-Bucy syndrome
1. Visual agnosia
2. Oral-exploratory behaviour
3. Tameness (amygdala)
4. Hypersexuality
5. Hypomotility
6. Hypermetamorphosis
3. Lateroinferior aspect
1. Transcortical sensory aphasia
2. W ord selection anomia
3. Agitated delirium
1. Impaired recognition of facial emotional
expression
4. Laterosuperior aspect
2. Sensory aphasia
1. Sensory amusia
2. Sensory aprosodia
3. Bilateral lesions
1. Auditory agnosia
4. Contralateral superior quadrantanopia
5. Nonlocalizing
1. Auditory hallucinations
2. Complex visual hallucinations
6. W ith epileptogenic lesions (mainly inferomedial)
1. Interictal manifestations (a–f below plus g. or
h.)
1. Deepening of emotions
2. Tendency to transcendentalize minutia
(cosmic vision)
3. Concern with minor detail
1. Hypergraphia
2. Circumstantiality
4. Paranoid ideation
5. Hyposexuality
6. Abnormal religiosity
7. Left hemispheric foci
1. Ideational aberration
2. Paranoia
3. Sense of personal destiny
8. Right hemispheric foci
1. Emotional disturbances (sadness,
elation)
2. Denial
2. Ictal manifestations
1. Hallucinations of smell and taste
(amygdala)
2. Visual delusions (déjà vu, jamais vu)
3. Experiential delusions (déjà vecu, jamais
vecu)
4. Psychomotor seizures (temporal lobe
variety of partial complex seizures)
3. Parietal Lobe
1. Postcentral gyrus
1. Simple somatosensory disturbances
1. Contralateral sensory loss (object
recognition > position sense > touch > pain
and temperature, vibration); tactile
extinction
2. Contralateral pain, paresthesias
2. Mesial aspect (cuneus)
1. Transcortical sensory aphasia? (dominant
hemisphere)
2. Attentional disorder
3. Lateral aspect (superior and inferior parietal
lobules)
1. Parietal apraxia (higher lesion)
2. Finger agnosia
3. Acalculia
4. Right-left disorientation
5. Literal alexia (supramarginal gyrus)
6. Conduction aphasia
1. Anosognosia
2. Autotopagnosia
3. Spatial disorientation
4. Hemispatial neglect (sensory inattention)
5. Constructional apraxia
6. Dressing apraxia
7. Loss of topographical memory
8. Allesthesia
9. Hemisomatognosia
10. Asymbolia for pain
4. Frontal Lobe
1. Precentral gyrus (motor area 4)
1. Face area (unilateral: transient: bilateral:
lasting)
1. Dysarthria
2. Dysphagia
2. Hand area
1. Contralateral weakness, clumsiness,
spasticity
3. Leg area (paracentral lobule)
1. Contralateral weakness
2. Gait apraxia
3. Urinary incontinence (lasting with bilateral
lesions)
2. Mesial aspect (F1 , cingulate gyrus)
1. Akinesia (bilateral akinetic mutism)
2. Perseveration
3. Hand and foot grasp
4. “Salutatory” seizures (“fencer's posture”)
5. Alien hand sign
6. Transcortical motor aphasia (dominant
hemisphere)
7. Difficulty with initiating contralateral arm
movements (may require initiation by
examiner)
8. Bilateral ideomotor apraxia (apraxia of
sequential acts)
3. Lateral aspect (premotor region)
1. Middle frontal gyrus (F2 )
1. Impaired contralateral saccades
2. Pure agraphia (dominant hemisphere)
3. Contralateral weakness of shoulder (mainly
abduction and elevation of arm) and hip
muscles plus limb-kinetic apraxia
4. Hemiakinesia (intentional neglect)
2. F 3
1. Motor aphasia (dominant hemisphere)
2. Motor aprosodia (nondominant hemisphere)
4. Frontal pole, orbitofrontal area (prefrontal)
1. Blunted affect (apathetic, indifferent)
2. Impaired appreciation of social nuances
3. Impaired goal-directed behavior
4. Impotence
5. Facetiousness (“witzelsucht” or moria)
6. Environmental dependency syndrome
7. apraxia of speech
8. Inability to plan and execute multistepped
processes
9. Abulia (poverty of thought, action, and
emotion) with large midline or bilateral
dorsofrontal lesions
5. Callosal Lesions
1. Lack of kinesthetic transfer
1. Inability to mimic position of the contralateral
hand
2. Left hand apraxia
3. Left hand agraphia
4. Right hand constructional apraxia
5. Intermanual conflict (alien left hand)
2. Perplexity (and confabulation) trying to explain
left-handed activity
3. Double hemianopia
4. Left hemiparalexia
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> Table of C ontents > C hapter 21 - Vas c ular S yndr om es of the For ebr ain, B r ains tem , and C er ebellum
Chapter 21
Vascular Syndromes of the Forebrain,
Brainstem, and Cerebellum
Vascular Supply of the Cerebral Hemispheres

The aort ic arch gives rise t o t hree major vessels: t he brachi ocephal i c, t he l ef t
common caroti d, and t he l ef t subcl avi an arteri es. The brachiocephalic in t urn
gives rise t o t he ri ght subcl avi an and t he ri ght common caroti d arteri es. The t w o
common carot id art eries run upw ard lat eral t o t he t rachea t o approximat ely t he
level of t he f ourt h cervical vert ebra, w here each bif urcat es int o t he external and
i nternal caroti d arteri es ( Fig 21-1). The t w o vertebral arteri es arise f rom t heir
respect ive subclavian art eries medial t o t he ant erior scalene muscle and join t o
f orm t he basi l ar artery. Af t er originat ing (f irst segment ) f rom t he subclavian
art ery, t he vert ebral art ery t raverses t he f oramina t ransversaria f rom C6 t o C2
(second segment ), loops around t he at lant o-occipit al joint (t hird segment ), and
f inally pierces t he dura passing t hrough t he f oramen magnum t o ent er t he
int racranial cavit y (f ourt h segment ) t o join t he ot her vert ebral art ery at t he
pont omedullary junct ion. The basilar art ery has a relat ively const ant course,
beginning at or slight ly below t he pont omedullary junct ion and st ret ching t he
lengt h of t he pons, t apering t o it s t erminat ion at t he pons–midbrain junct ion
w here it bif urcat es int o it s t w o t erminal branches, t he right and lef t posteri or
cerebral arteri es ( PCA), at t he level of t he int erpeduncular cist ern. The blood
supply of t he upper spinal cord, brainst em (medulla, pons, and midbrain),
labyrint h, cochlea, cerebellum, subt halamus, port ion of t he t halamus, and
t emporo-occipit al areas originat es f rom t he vert ebral–basilar syst em. The
carot id and vert ebral art ery syst ems join at t he base of t he brain t o f orm t he
circle of Willis.
The Internal Carotid Artery

The int ernal carot id art ery (I CA) may be divided int o t hree main segment s:
cervi cal , petrosal, and i ntracrani al . The cervi cal segment of t he I CA has no
branches. I t ascends vert ically in t he neck, ext ending f rom t he common carot id
bif urcat ion t o t he base of t he skull. I t t hen ent ers t he base of t he skull t hrough
t he carot id canal in t he pet rous port ion of t he t emporal bone. The art ery crosses
t he f oramen lacerum and ent ers t he cavernous sinus. The petrosal segment gives
off a carot icot ympanic branch (t o t he t ympanic cavit y) and a vidian branch
(art ery t o t he pt erygoid canal). The i ntracrani al segment begins dist al t o t he
pet rous segment and proximal t o t he ant erior clinoid process. Presellar and
juxt asellar port ions of t his vessel are dist inguished. The juxt asellar port ion lies
w it hin t he cavernous sinus in close proximit y t o t he oculomot or, t rochlear, and
abducens nerves (CN I I I , I V, and VI ), and t he opht halmic and maxillary divisions
of t he t rigeminal nerve (CN V). Meningohypophyseal branches (t ent orial art ery of
Bernasconi and Cassinari, dorsal meningeal art ery, and inf erior hypophyseal
art ery) arise f rom t he presellar and juxt asellar port ions t o supply t he adjacent
meninges and post erior lobe of t he hypophysis. The I CA t hen pierces t he dura
mat er medial t o t he ant erior clinoid process, w here it becomes t he supraclinoid.
The ophthal mi c artery, t he f irst major branch of t he I CA, arises at t he level of
t he ant erior clinoid process. This vessel runs init ially int racranially, t hen
t raverses t he opt ic canal en rout e t o t he orbit . The opht halmic art ery gives off
orbit al, ext raorbit al (et hmoidal branches t o t he dura of t he cribrif orm plat e and
planum sphenoidal and ant erior art ery of t he f alx), and
ocular branches; t he most import ant of t he ocular branches is t he central reti nal
artery. O t her ocular branches include t he long and short post erior ciliary art eries
and t he ant erior ciliary art eries. Rich anast omoses exist bet w een t he opht halmic
and t he ext ernal carot id art ery branches.
FI G URE 21-1 Comput ed t omography angiogram of t he carot id art ery

bif urcat ion
Af t er giving off t he opht halmic branch, t he I CA gives rise t o t he posteri or

communi cati ng artery and t hen t o t he anteri or choroi dal artery ( AChA). The
post erior communicat ing art ery joins t he post erior cerebral art ery t o f orm t he
post erolat eral port ion of t he circle of Willis. The post erior communicat ing
art eries may be large or t hreadlike and provide a link bet w een t he ant erior and
post erior circulat ions and bet w een t he t w o cerebral hemispheres. Penet rat ing
branches f rom t he post erior communicat ing art ery supply t he ant erior and
post erior hypot halamus, t he opt ic t ract and post erior port ion of t he opt ic chiasm,
and t he ant erior and vent ral t halamic nuclei. The AChA passes post erolat erally t o
reach t he opt ic t ract . When large, it s t errit ory includes t he choroid plexus of t he
t emporal horn, t he hippocampus and dent at e gyri, t he amygdaloid nucleus, t he
pirif orm cort ex and uncus of t he t emporal lobe, t he lat eral geniculat e body, t he
opt ic t ract and t he origin of t he opt ic radiat ions, t he genu and t he inf erior and
medial part s of t he post erior limb of t he int ernal capsule, t he globus pallidus, t he
t ail of t he caudat e nucleus, and t he upper brainst em (middle one-t hird of t he
cerebral peduncle and subst ant ia nigra).
Af t er giving off t he AChA, t he I CA t hen bif urcat es t o f orm t he anteri or cerebral
and mi ddl e cerebral arteri es.
The Anterior Choroidal Artery

The AChA vascularizes t he post erior limb (post erior t w o-t hirds) of t he int ernal
capsule, opt ic t ract , lat eral geniculat e body (hilum and lat eral part ), opt ic
radiat ion, amygdala, uncus and adjacent medial t emporal lobe, and post erior
paravent ricular corona radiat a.
The Anterior Cerebral Artery

The ant erior cerebral art ery (ACA) arises below t he ant erior perf orat ed
subst ance and runs ant eromedially t o t he int erhemispheric f issure, w here it joins
t he opposit e ACA by w ay of t he anteri or communi cati ng artery, closing t he
rost ral port ion of t he circle of Willis. The ACA supplies t he medial surf ace of t he
cerebrum and t he upper border of t he f ront al and pariet al lobes [18] . I t gives
origin t o (a) medi al l enti cul ostri ate branches, (b) peri cal l osal branches t o t he
corpus callosum, and (c) hemi spheri c branches. The medi al l enti cul ostri ate
branches include basal branches, w hich supply t he dorsal aspect of t he opt ic
chiasm and t he hypot halamus, and t he medial st riat e art ery (recurrent art ery of
Heubner), w hich supplies blood t o t he ant eroinf erior limb of t he int ernal capsule,
t he ant erior aspect s of t he put amen and caudat e nuclei, and t he t ip of t he out er
segment of t he globus pallidus. The callosal branches arise f rom t he peri cal l osal
artery, w hich is t hat port ion of t he ACA dist al t o t he ant erior communicat ing
art ery. O t hers reserve t he t erm peri cal l osal artery f or t he segment beyond t he
origin of t he callosomarginal art ery. The ACA and t he pericallosal art eries also
supply t he sept um pellucidum and t he f ornix. The hemi spheri c branches supply
t he medial surf ace of t he hemisphere and include t he orbit of ront al, f ront opolar,
int ernal f ront al (ant erior, middle, and post erior), paracent ral, and int ernal
pariet al (superior and inf erior) branches.
The Middle Cerebral Artery
The middle cerebral art ery (MCA), t he largest branch of t he I CA, arises below
t he medial part of t he ant erior perf orat ed subst ance. I t supplies most of t he
lat eral surf ace of t he cerebral hemisphere and t he deep st ruct ures of t he f ront al
and pariet al lobes [180] . Three segment s of t he MCA are recognized: proxi mal ,
Syl vi an, and di stal . From t he post erosuperior aspect of t he proxi mal segment
arise t he penet rat ing lent iculost riat e art eries, w hich nourish t he adjacent corona
radiat a, ext ernal capsule, claust rum, put amen, part of t he globus pallidus, body
of t he caudat e nucleus, and superior
port ion of t he ant erior and post erior limbs of t he int ernal capsule. O t her
branches t hat may arise f rom t he horizont al segment are t he orbit of ront al and
ant erior t emporal art eries, but many variat ions occur. The Syl vi an segment
consist s of all t he branches on t he insula of Reil and in t he Sylvian f issure. The
st em of t he MCA divides, generally in one of t hree pat t erns: (a) bif urcat ion
(78%), (b) t rif urcat ion (12%), or (c) ramif icat ion int o mult iple t runks (10%).
Theref ore, short ly af t er t he t akeoff of t he ant erior t emporal art ery, t he main
t runk of t he MCA most of t en bif urcat es, one branch giving rise t o t he anteri or or
proxi mal group of art eries and t he ot her branch t o t he posteri or or di stal group.
The anteri or group includes t he orbit of ront al, precent ral, cent ral, and ant erior
pariet al art eries. The posteri or group includes t he post erior pariet al, post erior
t emporal, and t he angular or t erminal art eries.
The Posterior Cerebral Artery

The PCA are t he t erminal branches of t he basilar art ery, alt hough approximat ely
25% of people have a f et al (embryonic) origin of t he PCA. The PCA arises f rom
t he rost ral end of t he basilar art ery w it hin t he int erpeduncular cist ern and
supplies t he occipit al lobes and t he inf eromedial port ions of t he t emporal lobes.
Numerous ot her branches supply t he mesencephalon, t halamus, and ot her
st ruct ures. The branches of t he PCA have been divided int o t hree groups [87] :
(a) t he penetrati ng arteri es t o t he brainst em, t halamus, and ot her deep
st ruct ures, (b) t he dorsal cal l osal artery, and (c) t he corti cal branches. From
t he origin of t he PCA (as it surrounds t he midbrain), numerous perf orati ng
branches are given off . Mesencephalic branches include t he int erpeduncular
perf orat ors and t he short and long circumf erent ial art eries. The art erial supply t o
t he t halamus arises f rom t he post erior communicat ing art eries and t he
perimesencephalic segment of t he PCA. The dorsal callosal art ery or splenial
branch anast omoses w it h dist al branches of t he ACA. The PCA has f our main
cort ical branches: t he ant erior t emporal, post erior t emporal, pariet o-occipit al,
and calcarine art eries. The calcarine art ery supplies t he visual cort ex.
Collateral Circulation
There are t hree main sources of collat eral circulat ion t o t he brain t hat
compensat e in cases of carot id or basilar occlusion: (a) t he circle of Willis,
locat ed on t he vent ral surf ace of t he brain, w hich connect s t he int ernal carot id
and vert ebrobasilar art erial syst ems w it h each ot her, (b) anast omoses bet w een
branches of t he ext racranial and int racranial art eries, and (c) lept omeningeal
anast omoses bet w een t he t erminal branches of t he major art eries of t he
cerebrum and cerebellum. The most import ant int racranial anast omoses are
t hose of t he circle of Willis. At ypical conf igurat ions of t he circle of Willis
result ing f rom hypoplasia of one or more component st ems is f ound in 79% of
individuals. Persist ent primit ive carot id basilar anast omoses may occur, such as
(a) primit ive t rigeminal art ery, (b) primit ive acoust ic (ot ic) art ery, (c) primit ive
hypoglossal art ery, and (d) primit ive proat lant ic art ery. A persist ent t rigeminal
art ery [68] is t he most f requent of t he f our primit ive connect ions (0. 1–0. 2% of
adult s) and may maint ain signif icant collat eral f low.
The art eries of t he brain and t heir main t errit ories of dist ribut ion are diagrammed
in Figures 21-2 and 21-3.
Syndromes of the Cerebral Arteries

Cerebrovascular disorders are t he result of eit her ischemia or hemorrhage w it hin
t he cent ral nervous syst em (CNS), and are broadly considered under t he t erm
stroke. A st roke is t he t hird most common cause of mort alit y in most developed
count ries. A st roke indicat es t he relat ively abrupt (seconds t o hours) onset of a
f ocal neurologic def icit result ing f rom disease (occlusion or rupt ure) of t he
art eries or veins t hat serve t he CNS. Alt hough st roke is commonly used t o mean
cerebral inf arct ion (CI ), it is pref erable t o use more precise t erms, such as CI ,
int racerebral hemorrhage (I CH), or subarachnoid hemorrhage (SAH). The
et iologic f act ors t hat may give rise t o a st roke are many.
The key w ord is f ocal ; ot her key f act ors are w het her t he def icit is t ransient or
permanent , st at ic or progressive, and w het her t he lesion is locat ed in t he
cerebral cort ex, subcort ical areas, brainst em, or cerebellum. The neurologic
def icit ref lect s t he locat ion and size of t he lesion. St roke syndromes may arise
f rom an inf arct or a hemorrhage. An inf arct is usually due t o eit her t hrombosis
f rom at herosclerot ic lesions or embolism f rom t he heart , aort a, or
ext racranial/ int racranial vasculat ure. Hemorrhage may be epidural, subdural,
subarachnoid, int ra-parenchymal, or int ravent ricular, and may have various
et iologies, including art erial hypert ension, saccular aneurysms, art eriovenous
malf ormat ions, blood dyscrasias, vasculit is, sympat homimet ic drugs, cerebral
amyloid angiopat hy, t rauma, or neoplasms.
FI G URE 21-2 The art eries of t he brain (basilar view ).
FI G URE 21-3 Major t errit ories of dist ribut ion of brain vessels.
Most cases of acut e st roke are ischemic, usually result ing f rom t hrombot ic or
embolic occlusion of a cerebral art ery. At herot hrombot ic and t hromboembolic
art erial occlusions account f or approximat ely 80% t o 85% of all cases. I CH is
responsible f or approximat ely 10% of all st rokes and SAH account s f or t he
remainder. Cerebral at herot hromboembolism involves predominant ly t he MCA,
f ollow ed by t he PCA t errit ory; t he ACA and t he basilar art ery are involved less
f requent ly. I n addit ion t o ext racranial occlusive cerebrovascular disease, sources
of cerebral embolism include recent myocardial inf arct ion w it h a mural t hrombus,
dilat ed cardiomyopat hies, at rial f ibrillat ion, sick sinus syndrome, rheumat ic
valvular heart disease, prost het ic heart valves, congenit al heart disease, cardiac
t umors, and inf ect ive and marant ic endocardit is.
Alt hough not pat hophysiologically usef ul, t he f ollow ing t emporal pat t erns of t he
st roke syndrome are of t en recognized: transi ent i schemi c attacks
(TIAs), “compl eted” stroke, and stroke i n evol uti on.
Transient Ischemic Attacks

TI As are pow erf ul f orerunners of st roke. Approximat ely 10% of pat ient s
diagnosed as having a TI A have a st roke in t he 90 days f ollow ing t he TI A
diagnosis, w it h half of t hem having a st roke w it hin 2 days of t he TI A [104] . TI As
are short -lived episodes of acut e, f ocal, nonconvulsive neurologic dysf unct ion
presumably caused by reversible ischemia t o an area of t he ret ina or brain.
O nset of sympt oms is sudden and of t en unprovoked, reaching maximum int ensit y
almost immediat ely. Because TI As commonly last 2 t o 30 minut es, pat ient s of t en
have no clinical manif est at ions by t he t ime t hey present f or medical at t ent ion
[ 212] . To qualif y as a TI A, t he episode should be f ollow ed by compl ete recovery,
and no neurologic residua should be det ect ed af t er 24 hours. TI As are of t en
associat ed w it h variable rat es of inf arct ion on comput ed t omography (CT) or
magnet ic resonance imaging (MRI ). Thereby, a separat e clinical syndrome of TI A
w it h inf arct ion, w it h diff erent prognost ic connot at ions, has been proposed [9] .
Because ident if icat ion of t he art erial t errit ory involved is import ant in considering
t he ext ent of invest igat ion and management , TI As involving t he ant erior or
carot id circulat ion should be separat ed f rom t hose involving t he post erior or
vert ebrobasilar circulat ion, alt hough such a dist inct ion is not alw ays f easible.
Most TI As have an embolic ipsilat eral carot id or cardiac source; hemodynamic
mechanisms are less common. Tw ent y-f ive percent of pat ient s w it h TI As
complain of headaches during t he at t ack.
TABLE 21-1 Symptoms of Transient Ischemic Attacks
Carotid Artery Vertebrobasilar Artery

Sym ptom Territory Territory a
Bilateral or shifting
Contralateral weakness, clumsiness,
Motor weakness, or paralysis; ataxia,
deficit clumsiness, or imbalance, or
paralysis disequilibrium not
associated with vertigo
Contralateral
Bilateral or shifting
numbness;
Sensory numbness;
paresthesias,
deficit paresthesias, including
including loss of
loss of sensation
sensation
Speech Dysphasia,
Dysarthria
deficit dysarthria
Ipsilateral
monocular
blindness Diplopia, partial, or
Visual (amaurosis complete blindness in
deficit fugax), both homonymous
contralateral visual fields
homonymous
hemianopia
Combination of Combination of the

Other
the above above
a Transient vertigo, diplopia, dysarthria, or dysphagia by
themselves are insufficient to establish a diagnosis of

vertebrobasilar artery territory transient ischemic
attacks.
Sympt oms considered t ypical of TI As in t he carot id and vert ebrobasilar syst em

are show n in Table 21-1.
“Completed” Stroke
A complet ed st roke is t he t erm applied t o t he t emporal prof ile of t he st roke
syndrome in w hich t he def icit is prolonged and of t en permanent , causing
demonst rable parenchymat ous changes. Most
complet ed st rokes reach t he maximum of neurologic dysf unct ion w it hin an hour of
onset .
Stroke in Evolution
St roke in evolut ion, progressive st roke, or ingravescent st roke describes t he
t emporal prof ile in w hich t he neurologic def icit occurs in a st epw ise or
progressive f ashion, culminat ing in a major def icit in t he absence of t reat ment .
Should t he sit e of ischemia be t he carot id art erial dist ribut ion, 24 hours w it hout
progression is usually enough t ime t o est ablish t hat f urt her progression is
unlikely. I f t he sit e of ischemia is t he vert ebrobasilar art erial syst em, how ever,
t he def icit may progress f or up t o 72 hours. Progression may result f rom
recurrent embolism, propagat ing int raluminal t hrombus, inadequat e collat eral
circulat ion, cerebral edema, int racranial hemorrhage, or int ercurrent medical
complicat ions.
The Carotid Artery Syndrome

The only f eat ure dist inguishing t he carot id art ery syndrome f rom t he MCA
syndrome is amaurosis f ugax or t ransient monocular blindness. Pat ient s w it h
amaurosis f ugax of t en describe t he sudden onset of t ransient painless monocular
loss of vision somet imes described as a “curt ain” or “shade” being pulled f rom
t he t op or bot t om of a visual f ield, or as a const rict ion of t he visual f ield, such as
an iris diaphragm t ype of monocular visual loss [98] . The f ormer t ype of spell is
most likely embolic, w hereas t he lat t er is most probably relat ed t o marginal
perf usion causing diminished blood f low t o t he ret ina. Not inf requent ly, t he
charact erist ics of t he at t acks of visual loss are described as a blackout ,
dimming, blurring, graying, or f ogging of vision. I n a subset of t he Nort h
American Sympt omat ic Carot id Endart erect omy Trial (NASCET), one-t hird of
pat ient s report ed an alt it udinal visual loss w it h an ascending or descending
shade [203] . Most at t acks are spont aneous and unrelat ed t o posit ional changes.
The lengt h of visual loss is approximat ely 1 t o 5 minut es; but rarely it may last
20 t o 30 minut es. During at t acks t he pupil is amaurot ic and t he ret inal vessels
collapse. I n evaluat ing t he pat ient , t he pupils should be dilat ed t o f acilit at e
examinat ion of t he peripheral ret ina. Amaurosis f ugax of t en result s f rom
embolism f rom t he carot id art ery, heart , or aort a, hypoperf usion,
hypercoagulable st at es, or vasospasm. Diff erent t ypes of microemboli can be
seen in t he ret inal art erioles during or bet w een at t acks of t ransient monocular
visual loss [238] . They are list ed in t he order of f requency in Table 21-2.
TABLE 21-2 M icroemboli in Carotid Artery Syndro
Vessel
Microem boli Appearance Origin Com
Occlusion
Irregular,
bright,
Bright
orange- May, may Eroded Cho
plaque
yellow, not atheroma crys
(Hollenhorst)
glistening,
refractile
Carotid
Grayish
thrombus, Plat
W hite plug white, Often
cardiac fibri
nonrefractile
source
Heart
Ovoid, gray-
Calcific valve or
white, Yes Calc
emboli calcified
nonrefractile
plaque
Unilat eral loss of vision in bright light (“bright -light ” amaurosis) may occur in
pat ient s w it h high-grade st enosis or occlusion of t he ipsilat eral carot id art ery
[ 75] . Episodic bilat eral vision impairment relat ed exclusively t o light exposure
may occur w it h bilat eral high-grade st enosis or occlusion of t he I CA [229] . Visual
loss may persist f or seconds t o hours af t er exposure and is t hought t o be
relat ed t o bilat eral simult aneous ret inal ischemia delaying regenerat ion of visual
pigment s in t he pigment epit helial layer.
The diff erent ial diagnosis of t ransient monocular visual dist urbances includes
ret inal ischemia (ret inal migraine, vasospasm, Raynaud's phenomenon,
amaurosis f ugax, anemia, polycyt hemia, sickle cell disease, carot id art ery
compression or occlusion, post ural hypot ension, cardiac arrhyt hmia); opt ic disc
elevat ion, dysplasia, or ischemia (int rapapillary drusen, opt ic nerve sheat h
meningioma, dysplast ic coloboma, papilledema, art erit is); and mechanical ret inal
or opt ic nerve
st imulat ion (oculodigit al phenomenon, light ning st reaks of Moore, opt ic neurit is,
ret inal t ear, f lick phosphenes) [40, 237] . At t acks of subacut e angle closure
glaucoma may also cause t ransient monocular visual loss [178] . Amaurosis f ugax
may also occur in associat ion w it h t he ant iphospholipid ant ibody syndrome [35,
60] and w it h exercise in healt hy young adult s (likely migraine equivalent s) [100] .
Pat ient s w it h mult iple sclerosis may also report uniocular or binocular dimming of
vision af t er exercise (Ut hoff sympt om) [195] . Amaurosis f ugax and ocular
inf arct ion in young adult s and adolescent s are associat ed w it h a more benign
clinical course t han t hose seen in older pat ient s and are likely caused by
migraine [210] . Rarely, an int raorbit al t umor may compress t he opt ic nerve or a
nut rient vessel in cert ain gaze posit ions, causing t ransient monocular visual loss.
At herot hrombot ic disease of t he carot id syst em has a predilect ion f or t he
bif urcat ion of t he common carot id art ery and t he proximal I CA, w hich is more
f requent among w hit es and in men, w hereas carot id art ery siphon st enosis is
more common among blacks and Asians. Pat ient s w it h carot id art ery occlusive
disease may present w it h recurrent TI As, an apoplect ic or st epw ise onset , or a
slow ly progressive neurologic def icit (pseudot umoral f orm). O cclusion of t he I CA
in t he neck may be t ot ally asympt omat ic in t he presence of adequat e collat eral
circulat ion, part icularly if t he occlusion develops slow ly. I nf arct ion of t he
homolat eral hemisphere may occur w hen t he collat eral circulat ion is inadequat e.
O cclusion of t he int racranial carot id art ery bif urcat ion (T port ion), usually result s
in large inf arct ions involving t he ant erior and t he MCA t errit ories. According t o
locat ion, inf arct s may involve t he ent ire t errit ory of t he MCA (t ot al), t he areas of
supply nearest t he I CA or MCA (proximal), t he border zone bet w een t he ACA and
MCA (w at ershed), or only t he w hit e mat t er supplied by peripheral branches of
t he MCA (t erminal). Pat ient s may init ially complain of localized or generalized
headaches, and f ocal seizures may occur. Cont ralat eral hemiplegia,
hemianest hesia, homonymous hemianopia, and aphasia (if t he dominant
hemisphere is compromised) or apract agnosia (if t he nondominant hemisphere is
involved) may ensue. The associat ion of amaurosis f ugax or ischemic opt ic
neuropat hy w it h cont ralat eral hemiplegia (opti co-cerebral syndrome) is rarely
seen [33] . Acut e I CA occlusion may also rarely cause concurrent
opht halmoparesis (t ransient ) w it h monocular blindness (permanent ) [232] .
Caref ul examinat ion may reveal an ipsilat eral part ial Horner syndrome, usually
t ransient , w hich is due t o compromise of t he sympat het ic f ibers coursing along
t he I CA. I psilat eral opt ic at rophy seldom occurs. I schemic oculopat hy (ocular
ischemic syndrome) can also be a manif est at ion of carot id art ery occlusive
disease [236] . Pat ient s w it h ischemic oculopat hy may complain of ocular or
orbit al pain of t en relieved by t he supine posit ion, decrease in vision, and “bright -
light ” amaurosis. There may be engorgement of conjunct ival and episcleral
vessels, corneal edema, ischemic pseudo-inf lammat ory uveit is, rubeosis iridis,
and ant erior chamber cells and f lare [155] . The int raocular pressure may be low
(early) or abnormally high (lat e). O ccasionally, t here may be asymmet ric
hypert ensive ret inal changes not ed on f unduscopy. Corneal arcus senilis may be
less apparent on t he side of low perf usion [196] . Venous st asis (hypot ensive)
ret inopat hy may occur w it h high-grade carot id st enosis or occlusion and is
charact erized by insidious onset , diminut ion or absence of venous pulsat ions,
dilat ed and t ort uous ret inal veins, midperipheral microaneurysms, blossom-
shaped hemorrhages in t he midperipheral ret ina, and nerve f iber layer splint er
hemorrhages. Hypot ensive ret inopat hy may also include ret inal art eriole
narrow ing, macular edema, and neovascularizat ion in t he post erior pole.
I n most cases, pat ient s present w it h unif orm (proport ionat e) hemiparesis (f ace,
shoulder, hand, hip, and f oot ), or f aciobrachial w eakness. O n rare occasions,
small cort ical inf arct s may account f or w eakness limit ed t o a part icular group of
digit s, part icularly t he index f inger [118, 122] .
The neurovascular examinat ion may disclose a w ell-localized brui t in t he mid- or
upper cervical area. Bruit s arise w hen normal laminar f low of blood is dist urbed,
usually w hen t he diamet er st enosis is >50%. How ever, t he presence of a cervical
bruit does not necessarily indicat e underlying carot id at herosclerosis.
Correlat ion w it h angiography or ult rasound st udies show only approximat ely 60%
agreement w it h cervical auscult at ion in predict ing t he presence of carot id
st enosis, and may act ually disappear w it h lesions causing diamet er st enosis of
>90%. Radiat ed cardiac murmurs, hyperdynamic st at es, nonat herosclerot ic
carot id art erial lesions, and venous hums can produce cervical murmurs. The
absence of a bruit has lit t le diagnost ic value. The bruit may disappear w hen t he
st enosis is >90%. Conversely, a cervical bruit may be heard cont ralat eral t o an
I CA occlusion.
Severe st enosis or occlusion of t he I CA may cause progressive or episodic
w eakness of one low er ext remit y, of t en aggravat ed or precipit at ed by st anding
or w alking [235] . This w eakness is t hought t o be due t o hypoperf usion in t he
border
zone bet w een t he ant erior and middle cerebral art eries. Also, episodic carot id
ischemia may rarely cause int ermit t ent limb shaking or repet it ive involunt ary
movement s [11, 234] . These movement s are brief , coarse, irregular or rhyt hmic,
w avering or t rembling, and aff ect one or bot h ext remit ies on one side (opposit e
t he side of major carot id at heromat ous disease). They are charact erist ically
precipit at ed by st anding up, w alking, or neck hyperext ension and are prompt ly
relieved by assuming t he supine or sit t ing posit ion and are t hought t o be due t o
t ransient hemodynamic ischemic episodes rat her t han epilepsy. O t her at ypical
carot id dist ribut ion t ransient ischemic manif est at ions include ort host at ic TI As,
t ransient anosognosia, and t ransient loss of pit ch percept ion [67] . I nf arct s of t he
genu of t he int ernal capsule may cause cont ralat eral f acial and lingual paresis
w it h dysart hria [31] . A clust er of TI As (capsular w arning syndrome) causing
w eakness of t he cont ralat eral hemibody and ref lect ing ischemia of a single
lent iculost riat e art ery may occur hours t o days bef ore a st roke [63] . This
capsul ar genu syndrome may also be associat ed w it h unilat eral mast icat ion-
palat al-pharyngeal w eakness, ipsilat eral vocal cord paresis, and mild hand
w eakness (hand paresis suggest s involvement of t he ant erior part of t he
post erior limb of t he int ernal capsule). This f aciolingual syndrome suggest s t hat
a majorit y of cort icopont ine and cort icobulbar f ibers t o t he f acial and
hypoglossal nuclei are locat ed in t he genu of t he int ernal capsule; t he absence of
st ernocleidomast oid paresis or sensory changes suggest s t hat cort icof ugal
f ibers t o t he nucleus of CN XI and t halamocort ical f ibers corresponding t o
buccof acial sensat ion do not t ravel in t he genu. The inconst ant mast icat ion,
pharyngeal, palat al, and laryngeal w eakness suggest bilat eral, alt hough
predominant ly unilat eral, cort icof ugal project ions t o t he mot or nuclei of CN V and
CN I X and t he nucleus ambiguus or cont rol of t hese f unct ions by ext racapsular
f ibers [31] . Faciolingual hemiparesis, w het her associat ed w it h masset er, palat al,
pharyngeal, laryngeal, or hand w eakness, is highly suggest ive of st roke limit ed
t o t he genu of t he cont ralat eral int ernal capsule. Pure dysart hria, somet imes w it h
cont ralat eral f acial w eakness, may occur w it h st riat ocapsular inf arct ion, w it h
inf arct ion of t he superior port ion of t he ant erior limb of t he int ernal capsule or
adjacent corona radiat a, w it h inf arct ion in t he superior port ion of t he genu or
adjacent corona radiat a, w it h inf arct s of t he bulbar mot or cort ex, or w it h
vert ebrobasilar inf arct ion [62, 95, 99] .
I nf arct ion involving t he genu of t he int ernal capsule has been report ed t o result in
behavioral changes [206] . Damage t o t he ant erior nucleus of t he t halamus, w hich
lies immediat ely inf eromedial t o t he genu of t he int ernal capsule, cannot be ruled
out in t hese cases. The acut e syndrome includes f luct uat ing alert ness,
inat t ent ion, memory loss, apat hy, abulia, and psychomot or ret ardat ion,
suggest ing f ront al lobe dysf unct ion. Cont ralat eral hemiparesis and dysart hria are
mild, except w hen t he inf arct ext ends t o involve t he post erior capsular limb.
Neuropsychological t est ing in pat ient s w it h lef t -sided inf arct s may reveal severe
verbal memory loss, occasionally associat ed w it h dement ia, w hereas right -sided
inf arct s cause t ransient impairment in visuospat ial memory. I t has been inf erred
t hat t he capsular genu inf arct int errupt s t he inf erior and ant erior t halamic
peduncles, result ing in f unct ional deact ivat ion of t he ipsilat eral f ront al cort ex
(t halamocort ical disconnect ion) [206] . O t her aut hors have f ailed t o see t his
syndrome w it h lesions in t he genu of t he int ernal capsule [31] .
The Anterior Choroidal Artery Syndrome

I nf arct ion in t he AChA t errit ory t ypically result s in hemiparesis due t o involvement
of t he pyramidal t ract in t he post erior limb of t he int ernal capsule, hemisensory
loss due t o involvement of t he superior t halamic radiat ions sit uat ed in t he
t halamolent icular port ion of t he post erior limb of t he int ernal capsule, and
homonymous hemianopia sparing t he horizont al meridian or quadruple
sect oranopia secondary t o involvement of t he opt ic t ract , t he lat eral geniculat e
body, t he opt ic radiat ions, or a combinat ion of t hese [38, 56, 97] . A relat ive
aff erent pupillary def ect may be present in t he eye cont ralat eral t o t he side of
t he lesion (opt ic t ract lesion). Clinical syndromes w it h AChA inf arct ion include a
pure mot or syndrome, a sensorimot or syndrome, and at axic hemiparesis [97] . CT
scan or MRI examinat ion reveals abnormalit y in t he post erior limb of t he int ernal
capsule, sparing t he t halamus medially and encroaching on t he t ip of t he globus
pallidus lat erally. A homonymous def ect in t he upper and low er visual f ields
sparing t he horizont al meridian is charact erist ic of a lesion in t he lat eral
geniculat e body in t he t errit ory of t he AChA [91] . I n a small percent age of
pat ient s, AChA t errit ory inf arct s on t he right side produce lef t spat ial
hemineglect , const ruct ional apraxia, anosognosia, and mot or impersist ence, and
t hose on t he lef t side produce a mild language disorder [28, 56] . Bilat eral AChA
inf arct ion may result in bilat eral capsular inf arct ion, causing acut e pseudobulbar
mut ism accompanied by varying degrees
of f acial diplegia, hemiparesis, hemisensory loss, let hargy, neglect , and aff ect
changes [92] . Bilat eral involvement of t he lat eral geniculat e bodies may cause
bilat eral hourglass-shaped visual f ield def ect s. Fit s of laught er or crying devoid
of emot ional cont ent have also been described w it h AChA t errit ory inf arct ions
[ 58] .
The Anterior Cerebral Artery Syndrome

Whet her embolic, t hrombot ic, or vasospast ic, occlusion of t he ACA is a rare
condit ion comprising 0. 6% t o 3% of CI s [30] . I nf arct ion in t he ACA t errit ory
causes damage primarily t o t he medial f ront al area. The clinical pict ure of an
ACA t errit ory inf arct ion varies according t o t he sit e of occlusion and t he
available collat erals [30, 52] . I nf arct ion in t he t errit ory of t he hemispheric
branches of t he ACA of t en result s in cont ralat eral w eakness involving primarily
t he low er ext remit y and, t o a lesser ext ent , t he arm (especially t he shoulder).
Pat ient s may display lack of init iat ive or abulia. Parat onia (gegenhalt en) is of t en
present . Bilat eral inf arct ion in t he dist ribut ion of t he ACA causing paraplegia is
rarely report ed; a t rue azygous ACA (solit ary unpaired vessel arising as a single
t runk f rom t he conf luence of t he horizont al segment s of t he right and lef t ACA)
does not appear t o be a f act or in t he pat hogenesis [156] . Wit h bilat eral damage
t o t he mesiof ront al region, pat ient s may exhibit akinet ic mut ism, paraplegia,
incont inence, and amnesia w it h apat hy [30] . Wit h involvement of t he ant erior
corpus callosum, t hey may have lef t arm apraxia (ant erior disconnect ion
syndrome). Sensory examinat ion may show cont ralat eral t act ile sensory loss
aff ect ing primarily t he low er ext remit y. A number of pat ient s have impaired
art iculat ion and a sof t w hispering voice. Wit h unilat eral lef t -sided lesions, t hey
may have t ranscort ical mot or aphasia. Some pat ient s exhibit memory and
emot ional dist urbances and impaired planning abilit ies. I n some cases t here are
dist urbances of sphinct er cont rol w it h urinary incont inence (t ransient w it h
unilat eral lesions). Some pat ient s demonst rat e gait and post ural disorders.
Dominant medial f ront al damage t hat includes t he supplement ary mot or cort ex
may cause a dist urbance of upper ext remit y cont rol, including impaired bimanual
coordinat ion, t he alien hand sign, and int ermanual conf lict [148] . Large right ACA
inf arct ions may cause a hemiplegia w it h t he arm and leg aff ect ed more t han t he
f ace, marked sensory neglect , impaired copying and micrographia [131] .
Leg-predominant w eakness w it h st roke is due t o ACA inf arct ion in only 25% of
t he cases. More of t en, it is relat ed t o lesions in t he corona radiat a or int ernal
capsule, in t he t errit ory of t he AChA or perf orat ors (approximat ely 30%), or in
t he brainst em (approximat ely 25%) and can occur w it h lesions in t he MCA
t errit ory or w it h t halamic hemorrhage [189] . Regarding lesions in t he medial
aspect of t he f ront al lobe, t hose rest rict ed t o t he precent ral gyrus port ion of t he
paracent ral lobule cause a cont ralat eral, predominant ly dist al leg w eakness.
Lesions involving, in addit ion t o t he precent ral gyrus, t he premot or cort ex and
t he supplement ary mot or area cause leg w eakness, predominant ly dist al, and
less severe proximal w eakness of t he arm. Lesions aff ect ing t he medial part of
t he premot or cort ex and t he supplement ary mot or area, w hile sparing t he
precent ral gyrus, cause a cont ralat eral hemiparesis, more pronounced in t he leg,
and predominat ing proximally in bot h leg and arm. Lesions of t he int ernal capsule
or brainst em cause proport ional leg w eakness. The w eakness of t he legs w it h
t hese capsular and brainst em st rokes suggest a somat ot opic organizat ion of t he
pyramidal t ract s, w it h t he leg f ibers being probably dorsolat erally sit uat ed and
t he arm f ibers sit uat ed vent romedially [189] .
The syndrome of homolat eral at axia and crural paresis, w it h hemiparesis t hat
predominat es in t he leg and homolat eral at axia in t he arm, can occur w it h
superf icial ACA inf arct s in t he paracent ral area [27] . I nvolvement of t he
cort icopont ocerebellar f ibers at t heir origin along w it h damage t o t he low er limb
mot or st rip or underlying w hit e mat t er appear t o cause t his clinical syndrome in
t hese cases. At axic hemiparesis has also been described w it h lesions of t he
pons, corona radiat a, t halamus, lent if orm nucleus, or ot her st ruct ures.
I nf arct ion in t he t errit ory of t he medi al l enti cul ostri ate artery ( artery of Heubner)
result s in cont ralat eral w eakness of t he f ace and arm w it hout accompanying
sensory loss. Theref ore, w it h proximal ACA inf arct ion, severe cont ralat eral
hemiplegia may result , w it h paralysis of t he f ace, t ongue, and arm f rom damage
t o t he ant erior limb of t he int erior capsule and paralysis of t he leg f rom
paracent ral damage. I nf arct ion of t he basal branches of t he ACA cause t ransient
memory disorders, anxiet y, and agit at ion. Pat ient s w it h occlusion of t he
pericallosal branches may show apraxia, agraphia, and t act ile anomia of t he lef t
hand. Dist al occlusion of t he ACA may cause inf arct ion localized t o t he caudate
nucl eus (occasionally ext ending t o involve t he ant erior limb of t he int ernal
capsule and ant erior put amen), result ing in slight , t ransient hemiparesis,
dysart hria, behavioral and cognit ive def icit s (e. g. , agit at ion, hyperact ivit y, abulia,
cont ralat eral neglect ), and language impairment [43] .
Movement disorders are unusual f ollow ing ACA t errit ory inf arct s. A minorit y of
pat ient s w it h small ant erior f ront al lesions may exhibit ast erixis.
Hemiparkinsonism has been f ound w it h lesions involving t he supplement ary mot or
area or cingulat e gyrus. Micrographia has also been described w it h ACA inf arct s
[ 117, 131] .
The Middle Cerebral Artery Syndrome

The MCA is t he largest branch of t he I CA and a cont inuat ion of t his art ery in t he
direct ion of t he sylvian f issure. The MCA t errit ory is t he most common sit e of
ischemic st roke. The clinical pict ure of MCA t errit ory inf arct ion varies according
t o t he sit e of occlusion (e. g. , st em, superior division, inf erior division,
lent iculost riat e branches) and t he available collat erals. The clinical f eat ures of
inf arct ion occurring in t he MCA t errit ory are ext remely varied (e. g. , complet e
MCA t errit ory, deep t errit ory, superf icial ant erior [ superior] t errit ory, and
superf icial post erior [ inf erior] t errit ory) [90, 153, 225] .
Cont ralat eral w eakness aff ect ing t he f ace, t he arm, and, t o a lesser ext ent , t he
leg is a common manif est at ion of MCA t errit ory inf arct ion. Similarly, cont ralat eral
hemisensory loss involving t he f ace, t he arm, and, t o a lesser ext ent , t he leg is
also f requent . Perioral and dist al upper limb sensory dysf unct ion (cheiro-oral
syndrome) may occur [25] . Alt hough t he cheiro-oral syndrome has been
at t ribut ed t o a lesion of t he cont ralat eral post cent ral gyrus, it may also be seen
w it h lesions of t he cont ralat eral corona radiat a [165] or t halamus [110] , and even
w it h brainst em lesions [7, 86, 144, 166] . At axic hemiparesis w it h cheiro-oral
syndrome may occur w it h a cont ralat eral post erior capsular inf arct ion [51] .
Wit h MCA t errit ory inf arct ion, t here may be paresis and apraxia of conjugat e
gaze t o t he opposit e side, w it h t ransient t onic deviat ion of t he eyes and head
t ow ard t he side of t he lesion. I nf arct s in t he dominant hemisphere f or language
can be f ollow ed by Broca's, Wernicke's, conduct ion, or global aphasia,
depending on t he sit e and ext ent of involvement . Alexia w it h agraphia may occur
w it h t he involvement of t he lef t angular gyrus. Combinat ions of f inger agnosia,
acalculia, right –lef t disorient at ion, and agraphia (G erst mann's syndrome) may be
encount ered. I nf arct ion in t he nondominant hemisphere causes inat t ent ion,
neglect , denial, apract ic syndromes, and impaired prosody. Rarely, nondominant
inf arct ion may cause an acut e conf usional st at e and acut e agit at ed delirium w it h
aff ect ive and aut onomic excit ement , delusions, and hallucinat ions [159] . Lesions
of eit her hemisphere may give rise t o cont ralat eral homonymous hemianopia or
cont ralat eral homonymous inf erior quadrant anopsia. Cat alept ic post uring in
isolat ion f rom ot her manif est at ions of t he cat at onic syndrome has been
ment ioned in associat ion w it h MCA t errit ory inf arct ion [187] .
O cclusion of t he lat eral st riat e branches of t he MCA causes st riat ocapsular
inf arct ion w it h t he involvement of t he rost ral aspect of t he head of t he caudat e,
t he ant erior limb of t he int ernal capsule, and t he put amen (a comma-shaped area
on CT scan or MRI ) [62] . Clinical manif est at ions include hemiparesis, aff ect ing
mainly t he upper limb, and “cort ical” abnormalit ies (aphasia, neglect , and
dyspraxia). Less f requent ly, a pure mot or hemiparesis w it h minimal cort ical signs
may be seen and, rarely, subt le changes such as dysart hria alone or upper limb
clumsiness may occur. Causes of st riat ocapsular inf arct ion include cardioembolic
disease and occlusive vascular disease, more of t en in t he int ernal carot id t han in
t he MCA [62] .
The cent rum ovale, w hich cont ains t he core of t he hemispheric w hit e mat t er,
receives it s blood supply f rom t he superf icial (pial) MCA syst em t hrough
perf orat ing medullary branches, w hich course t ow ard t he lat eral vent ricles.
Pat ient s w it h inf arct s involving t he cent rum ovale limit ed t o t he t errit ory of t he
perf orat ing medullary branches w it hout t he involvement of t he lent iculost riat e
t errit ory of t en have large inf arct s associat ed w it h severe disease of t he
ipsilat eral carot id art ery and w it h acut e neurologic–neuropsychological
impairment no diff erent f rom t hat w it h large MCA inf arct ion. Small inf arct s are
associat ed w it h hypert ension or diabet es and w it h “lacunar syndromes, ” usually
of progressive onset [32] .
Doubl e (mult iple) inf arct s of t he MCA t errit ory of t he dominant hemisphere may
result in global aphasia w it hout hemiparesis [216] , hemianopic hemiplegia
w it hout sensory impairment [24] , or conduct ion aphasia w it h hemiparesis [24] .
Complet e MCA t errit ory inf arct ions have a poor out come and may result in
severe hemiparesis, f orced eye and head deviat ion, ipsilat eral or cont ralat eral
pupillary dilat at ion, a progressive diminishing level of consciousness secondary
t o space-occupying ischemic brain edema, brain shif t s, and subsequent
herniat ion [85] . Large MCA t errit ory inf arct ion is of t en associat ed w it h I CA
occlusion, cardiogenic embolism, or I CA dissect ion [90] .
Vertebrobasilar Artery Syndromes of the Brainstem and

Cerebellum
The dominant art erial t errit ories of t he brainst em and cerebellum have been
caref ully delineat ed by Tat u et al. [207] . The main art erial t runks supplying t he
brainst em include t he vert ebral art ery, ant erior spinal art ery, post erior inf erior
cerebellar art ery (PI CA), basilar art ery, ant erior inf erior cerebellar art ery,
superior cerebellar art ery, post erior cerebral art ery, post erior communicat ing
art ery, and AChA The cerebellar art erial supply depends on t he PI CA, t he
ant erior inf erior cerebellar art ery, and t he superior cerebellar art ery.
Connect ed t o t he brainst em by t hree pairs of cerebellar peduncles, t he main
sympt oms of cerebellar inf arct ion include vert igo, dizziness, nausea, vomit ing,
gait unst eadiness, limb clumsiness, headache, dysart hria, diplopia, and
decreased alert ness. Most prominent signs include limb and gait at axia,
dysart hria, nyst agmus, and alt ered ment al st at us [21] .
The areas of t he cerebellum supplied by t he PI CA are variable. The PI CA
vascularizes t he inf erior vermis and t he inf erior and post erior aspect s of t he
cerebellar hemispheres. There are several diff erent pat t erns of PI CA t errit ory
cerebellar inf arct ions. I f t he medial branch t errit ory is aff ect ed, involving t he
vermis and vest ibulocerebellum, t he clinical f indings include prominent vert igo,
at axia, and nyst agmus. I f t he lat eral cerebellar hemisphere is involved, pat ient s
can have vert igo, gait at axia, limb dysmet ria and at axia, nausea, vomit ing,
conjugat e or dysconjugat e gaze palsies, miosis and dysart hria. I f t he inf arct ion
is large, let hargy may occur. Hydrocephalus or herniat ions may develop. Wit h a
cerebellar pressure cone (t onsillar hernia) t here is dow nw ard displacement of
t he cerebellar t onsils t hrough t he f oramen magnum, result ing in hemorrhagic
necrosis of t he cerebellar t onsils and grooving of t he vent ral surf ace of t he
medulla oblongat a. Clinical manif est at ions may include neck st iff ness, cardiac
and respirat ory rhyt hm dist urbances, and apnea. Wit h ascending t ranst ent orial
herniat ion (upw ard herniat ion syndrome), t here is upw ard displacement of t he
superior aspect of t he cerebellar hemisphere t hrough t he f ree edge of t he
t ent orial incisura, result ing in midbrain compression. Clinical manif est at ions
include let hargy, coma, paralysis of upw ard gaze, midposit ion and unreact ive
pupils, and abnormal ext ensor post uring. There is also a syndrome of combined
dorsolat eral medullary and cerebellar inf arct ion t hat may be caused by a
vert ebral art ery occlusion or a medial PI CA occlusion. Alt hough a PI CA occlusion
can be t he cause of Wallenberg (lat eral medullary) syndrome, t his syndrome is
more of t en caused by an int racranial vert ebral art ery occlusion.
The ant erior inf erior cerebellar art ery syndrome causes a vent ral cerebellar
inf arct ion. This art ery vascularizes t he ant erior surf ace of t he simple, superior
and inf erior semilunar lobules and f locculus, as w ell as t he middle cerebellar
peduncle and of t en t he low er aspect of t he pont ine t egment um. The signs and
sympt oms include vert igo, nausea, vomit ing, and nyst agmus caused by
involvement of t he vest ibular nuclei. There may be ipsilat eral f acial hypalgesia
and t hermoanest hesia and corneal hypest hesia because of t he involvement of t he
t rigeminal spinal nucleus and t ract . I psilat eral deaf ness and f acial paralysis
occurs because of t he involvement of t he lat eral pont omedullary t egment um. An
ipsilat eral Horner syndrome is present because of t he compromise of t he
descending oculosympat het ic f ibers. Cont ralat eral t runk and ext remit y hypalgesia
occursand t hermoanest hesia is caused by t he involvement of t he lat eral
spinot halamic t ract . Finally, ipsilat eral at axia and asynergia is caused by t he
involvement of t he cerebellar peduncle and cerebellum. I nf arct s in t he
dist ribut ion of t he ant erior inf erior cerebellar art ery may be f orerunners of a
basilar art ery occlusion [4] . The superior cerebellar art ery vascularizes t he
superior half of t he cerebellar hemisphere and vermis, dent at e nucleus, and
upper aspect of t he pont ine t egment um. I nf arct ion in t he t errit ory of t he superior
cerebellar art ery produces a dorsal cerebellar syndrome. Vert igo may be
present , alt hough it is less common w it h superior cerebellar art ery inf arct s t han
w it h ot her cerebellar syndromes. Nyst agmus is caused by t he involvement of t he
medial longit udinal f asciculus and t he cerebellar pat hw ays. An ipsilat eral Horner
syndrome is caused by t he involvement of t he descending oculosympat het ic
t ract . I psilat eral at axia and asynergia and gait at axia are caused by t he
involvement of t he superior cerebellar peduncle, brachium pont is, superior
cerebellar hemisphere, and dent at e nucleus. There is an int ent ion t remor caused
by t he involvement of t he dent at e nucleus and superior cerebellar peduncle.
Choreif orm dyskinesias may be present ipsilat erally. Cont ralat erally, t here is
hearing loss caused by lat eral lemniscus disrupt ion and t runk and ext remit y
hypalgesia, and t hermoanest hesia caused by spinot halamic t ract involvement .
Pat ient s w it h superior cerebellar art ery t errit ory inf arct ion may
also experience ocular cont rapulsion (eyes pushed aw ay f rom side of t he lesion)
[ 177] .
The midbrain is vascularized by paramedian basilar art ery branches,
mesencephalic PCA branches, superior cerebellar art ery branches, and post erior
choroidal art ery branches [26, 192] . The midbrain cont ains t he nuclei f or t he
oculomot or (I I I ), t rochlear (I V), and port ions of t rigeminal (V) complex. Weber's
syndrome is caused by inf arct ion in t he dist ribut ion of t he penet rat ing branches
of t he PCA aff ect ing t he cerebral peduncle, especially medially, w it h damage t o
t he f ascicle of CN I I I and t he pyramidal f ibers. The result ant clinical f indings are
cont ralat eral hemiparesis caused by cort icospinal and cort icobulbar t ract
involvement and ipsilat eral oculomot or paresis, including a dilat ed pupil. A slight
variat ion of t his syndrome is t he midbrain syndrome of Foville in w hich t he
supranuclear f ibers f or horizont al gaze are int errupt ed in t he medial cerebral
peduncle, causing a conjugat e palsy t o t he opposit e side. Benedikt 's syndrome is
caused by a lesion aff ect ing t he mesencephalic t egment um in it s vent ral port ion,
w it h t he involvement of t he red nucleus, brachium conjunct ivum, and f ascicle of
CN I I I . This syndrome is caused by inf arct ion in t he dist ribut ion of t he
penet rat ing branches of t he PCA t o t he midbrain. The clinical manif est at ions are
an ipsilat eral t hird nerve paresis, usually w it h pupillary dilat ion, and a
cont ralat eral hemit remor, hemiat het osis, or hemichorea. Claude's syndrome
(f eat uring element s of bot h Benedikt 's and Not hnagel's syndromes) is caused by
lesions t hat are more dorsally placed in t he midbrain t egment um t han in
Benedikt 's syndrome. There is injury t o t he dorsal red nucleus, w hich result s in
more prominent cerebellar signs (asynergia, at axia, dysmet ria, and
dysdiadochokinesia) w it hout t he involunt ary movement s. Not hnagel's syndrome is
charact erized by an ipsilat eral t hird nerve paresis w it h cont ralat eral cerebellar
at axia. Not hnagel's syndrome is caused by a lesion in t he area of t he superior
cerebellar peduncle, in t he dist ribut ion of t he penet rat ing branches of t he PCA t o
t he midbrain, and may represent a variant of t he dorsal midbrain syndrome
[ 140] . Parinaud's (dorsal midbrain syndrome, pret ect al syndrome, Sylvian
aqueduct syndrome) syndrome can result f rom inf arct ions in t he midbrain
t errit ory of t he PCA penet rat ing branches. This syndrome is charact erized by
supranuclear paralysis of vert ical gaze, def ect ive convergence, spasm/ paresis of
accommodat ion, convergence–ret ract ion nyst agmus, light -near dissociat ion of
t he pupils, lid ret ract ion (Collier's sign), and skew deviat ion.
Pure mot or hemiparesis, f our-limb at axia, and hypest hesic at axic hemiparesis
caused by midbrain lesions are discussed w it h lacunar syndromes. O t her
inf arct ions in t he dist ribut ion of t he penet rat ing branches of t he PCA t o t he
midbrain may be charact erized by nuclear oculomot or palsy, unilat eral or
bilat eral int ernuclear opht halmoplegia, pseudoabducens palsy, and locked-in
syndrome [41] . Parkinsonism and micrographia have rarely been observed in
pat ient s w it h midbrain and t halamomesencephalic st rokes [127] .
At herot hrombot ic disease in t he vert ebrobasilar syst em has a predilect ion f or t he
dist al vert ebral art ery and t he low er or middle basilar art ery [188] .
At herosclerot ic involvement of t he int racranial port ion of t he vert ebrobasilar
syst em f requent ly occurs in t andem w it h and is t he common pat hologic
mechanism associat ed w it h t he syndrome of vert ebrobasilar inf arct ion. Top of
t he basilar or rost ral basilar art ery syndrome [41] is caused by inf arct ion of t he
midbrain, t halamus, hypot halamus, paramedian diencephalon, medial t emporal
lobes and occipit al lobes [150] . I t is caused by occlusive vascular disease, of t en
embolic in nat ure of t he rost ral basilar art ery. The f ollow ing signs may occur:
Behavi oral abnormal i ti es include somnolence, memory dist urbances, or agit at ed
delirium. Peduncular hallucinosis, report ed w it h f ocal lesions of t he cerebral
peduncles or w it h bilat eral involvement of t he medial aspect of t he subst ant ia
nigra pars ret iculat a and charact erized by complex, nont hreat ening visual
hallucinat ions, may also be present [78, 147] .
O phthal mol ogi c f i ndi ngs include unilat eral or bilat eral paralysis of upw ard or
dow nw ard gaze, impaired convergence, pseudoabducens palsy, convergence–
ret ract ion nyst agmus, abnormalit ies of ocular abduct ion, Collier's sign, skew
deviat ion, and oscillat ory eye movement s. Visual f ield def ect s t hat may be
present include homonymous hemianopia or quadrant anopia, cort ical blindness,
and Balint 's (psychic paralysis of gaze f ixat ion, simult anagnosia, opt ic at axia,
and visual inat t ent ion or disorient at ion) syndrome. Alexia w it hout agraphia may
be seen w it h dominant occipit al lesions. Bilat eral lesions may produce visual
agnosia or prosopagnosia. Pupillary abnormalit ies include small and react ive
pupils, large or midposit ion and f ixed pupils, and occasionally midbrain
corect opia charact erized by eccent ric or oval pupils.
Motor and sensory def icit s may likew ise occur. Alt hough t here are many named
classic pont ine syndromes (e. g. , Millard-G ubler, Raymond, Foville's, Raymond-
Cest an, Marie-Foix) t he most
usef ul cat egorizat ion is based on neuroanat omical divisions (vent ral, t egment al,
and bilat eral) [14] . Pont ine inf arct s can cause pure mot or hemiparesis,
sensorimot or st roke, at axic hemiparesis, dysart hria–clumsy hand syndrome,
at axic t et raparesis, or bilat eral cerebellar at axia [136] . Pont ine inf arct ions may
produce combined mot or, sensory, cerebellar, and cranial nerve dysf unct ion. The
pons cont ains t he nuclei f or t he abducens (CN VI ), f acial (CN VI I ),
vest ibulocochlear (CN VI I I ), and a port ion of t he nuclei of t he t rigeminal (CN V)
nerve. Locked-in syndrome (“vent ral pont ine syndrome” or “de-eff erent ed st at e”)
is t he result of bilat eral dest ruct ion usually at t he level of t he basis pont is
involving t he rost ral and middle pont ine segment s int errupt ing t he descending
cort icobulbar and cort icospinal t ract s, causing quadriplegia, aphonia, anart hria,
and impairment of t he horizont al eye movement s. Wakef ulness is maint ained
because of sparing of t he ascending ret icular f ormat ion. The pat ient can move
his or her eyes vert ically and can blink because t he supranuclear ocular mot or
pat hw ay lies more dorsally. Pupillary react ivit y is spared. Respirat ory f unct ion
remains int act . Most cases are due t o t hrombot ic or embolic occlusion of t he
basilar art ery. I n some pat ient s t here is a “heralding” hemiparesis t hat may be
misleading, making t he lesion seem cort ical in nat ure. How ever, w it hin a f ew
hours, t here is progression t o bilat eral hemiplegia and cranial nerve f indings
associat ed w it h t he locked-in syndrome [171] . Pat hologic laught er (Fou ri re
prodromi que) may herald t he development of a brainst em st roke as a result of
basilar art ery occlusion [82] . Pure mot or hemiparesis and at axic hemiparesis
caused by pont ine lesions are discussed w it h lacunar syndromes.
O cclusion of t he ant erior inf erior cerebellar art ery can lead t o t he lat eral inf erior
pont ine syndrome. Findings associat ed w it h t his syndrome include ipsilat eral
f acial paralysis, impaired f acial sensat ion, paralysis of conjugat e gaze t o t he
side of t he lesion, deaf ness, t innit us, and at axia. Cont ralat eral t o t he lesion,
t here is hemibody impairment t o pain and t emperat ure, w hich in some inst ances
includes t he f ace. There may be horizont al and vert ical nyst agmus and
oscillopsia. Bilat eral sudden deaf ness may be t he heralding manif est at ion of an
ant erior inf erior cerebellar art ery inf arct ion [137] . The medial inf erior pont ine
syndrome is caused by occlusion of a paramedian branch of t he basilar art ery.
Wit h t his syndrome, t here is ipsilat eral paralysis of conjugat e gaze t o t he side of
t he lesion, abducens nerve palsy, nyst agmus, and at axia. Cont ralat eral t o t he
lesion, t here is hemibody impairment of t act ile and propriocept ive sensat ion and
paralysis of t he f ace, arm, and leg. An occlusion of t he ant erior inf erior
cerebellar art ery may lead t o t he t ot al unilat eral inf erior pont ine syndrome, a
combinat ion of t he sympt oms and signs seen w it h t he lat eral and medial pont ine
syndromes.
The lat eral pont omedullary syndrome can occur w it h t he occlusion of t he
vert ebral art ery.
The manif est at ions are a combinat ion of t he medial and lat eral inf erior pont ine
syndromes. O cclusion of t he paramedian branches of t he midbasilar art ery can
lead t o ipsilat eral impaired sensory and mot or f unct ion of t he t rigeminal nerve
w it h limb at axia, charact erist ics of t he lat eral midpont ine syndrome. I schemia of
t he median pont ine region is caused by occlusion of t he paramedian branch of
t he midbasilar art ery and can lead t o ipsilat eral limb at axia. Cont ralat eral t o t he
lesion, eye deviat ion and paralysis of t he f ace, arm, and leg occur. Alt hough
t here are predominant mot or sympt oms, w hich predominat e in t he upper
ext remit y because of t he somat ot opic organizat ion of t he cort icospinal t ract in
t he basis pont is, variable impaired t ouch and propriocept ion may also occur.
Paramedian pont ine base lesions may also result in dysart hria. The lat eral
superior pont ine syndrome may occur w it h t he occlusion of t he superior
cerebellar art ery and produces a charact erist ic ipsilat eral Horner syndrome,
horizont al nyst agmus, paresis of conjugat e gaze, occasional deaf ness, and
severe gait and limb at axia. Cont ralat eral t o t he lesion, t here is hemibody
impaired sensat ion t o pain and t emperat ure, skew deviat ion, and impaired
t act ile, vibrat ory, and propriocept ive sensat ion in t he leg great er t han in t he arm.
Pont ine inf arct ions may also produce t ransient pat hologic crying and laught er
[ 127] , horizont al gaze abnormalit ies including abducens nerve palsy, I NO ,
horizont al gaze palsy, a one-and-a-half syndrome [108] , numbness and
hypest hesia of t he midline f acial region [143] , isolat ed volit ional t ype of f acial
palsy [213, 220] , and unilat eral hyperhydrosis [172] . The medulla oblongat a
cont ains t he nuclei f or t he glossopharyngeal (CN I X), vagus (CN X), and
hypoglossal (CN XI I ), as w ell as port ions of t he t rigeminal (CN V) nuclei,
vest ibulocochlear (CN VI I I ), and spinal accessory (CN XI ) nerves. The lat eral
medullary syndrome (Wallenberg syndrome) is most of t en caused by
at herosclerot ic occlusion or dissect ion of t he int racranial segment of t he
vert ebral art ery. Less commonly it is caused by occlusion of PI CA, small vessel
inf arct ion or cardiac embolism [119] . Dissect ions w ere more f requent w it h
caudally
placed medullary lesions. Depending on t he ext ent of t he medullary damage,

clinical f indings vary considerably [53] . Wallenberg syndrome consist s of a
const ellat ion of signs and sympt oms including ipsilat eral limb and gait at axia w it h
a t endency t o f all t o t he ipsilat eral side (body lat eropulsion) due t o involvement
of t he rest if orm body and inf erior surf ace of t he cerebellar hemisphere. There is
ipsilat eral f acial hypalgesia and t hermoanest hesia because of involvement of t he
descending t ract and nucleus of t he t rigeminal nerve. There is paresis of t he
pharyngeal muscles w it h palat al w eakness, decreased gag ref lex, dysphagia,
and dysphonia due t o ipsilat eral vocal cord paresis caused by t he involvement of
t he nucleus ambiguus. An ipsilat eral Horner syndrome is present because of
compromise of t he descending oculosympat het ic pat hw ays. Cont ralat eral t runk
and ext remit y hypalgesia and t hermoanest hesia occurs caused by involvement of
t he spinot halamic t ract . These pat ient s experience vert igo and of t en an
illusionary t ilt ing of t he environment by 90 t o 180 degrees. Nyst agmus and a host
of oculomot or sympt oms may be caused by compromise of t he ipsilat eral
vest ibular nuclei or f unct ional compromise of t he f ast igial nucleus. Pat ient s may
demonst rat e a horizont al rot at ory jerk nyst agmus, beat ing aw ay f rom t he side of
t he lesion; t he nyst agmus eit her st ops or reverses w it h eye closure [64] . There
may be gaze-evoked nyst agmus, seesaw nyst agmus, impaired cont ralat eral
pursuit eye movement s, saccadic lat eropulsion, ocular lat eropulsion [93, 130,
132, 197] , skew deviat ion, and ipsilat eral horizont al gaze deviat ion.
The classic sensory signs of Wallenberg syndrome, due t o involvement of t he
crossed lat eral spinot halamic t ract and t he ipsilat eral descending t ract and
nucleus of t he t rigeminal nerve, include t he loss of pain and heat sensat ion in t he
ipsilat eral f ace and cont ralat eral hemibody and ext remit ies. How ever, numerous
variant s of t his classic sensory pat t ern have been recognized, including
cont ralat eral or bilat eral f acial sensory changes due t o t he involvement of t he
ascending as w ell as t he descending t rigeminal f ibers, part ial involvement of t he
f ace, changes in t he sensory level of t he t runk, sensory changes in t he ipsilat eral
ext remit ies, and hemisensory loss of t he cont ralat eral w hole hemibody [55, 107,
121, 124, 129, 145, 223] .
As a rare occurrence, some pat ient s w it h Wallenberg syndrome display
ipsilat eral f acial palsy presumably due t o t he involvement of an aberrant
cort icobulbar t ract , or ext ension of t he inf arct t o t he pons w it h compromise of
t he f acial nerve nucleus or f ascicles; emot ional-f acial paresis relat ed t o
involvement of looping medullary cort icof acial project ions in t he upper medulla
[ 44] ; ipsilat eral hemiplegia (O palski syndrome) due t o submedullary ext ension;
ipsilat eral w ild arm at axia probably relat ed t o involvement of t he lat eral cuneat e
nucleus [54] ; clumsiness of t he ipsilat eral upper limb result ing f rom ext ension of
t he lesion int o t he subolivary area [36] ; cent ral pain combining t hermal
hypest hesia w it h t hermal and t ouch allodynia [175] ; isolat ed cont ralat eral
t hermoanest hesia of t he t runk and limbs f rom involvement of t he dorsal port ion
of t he lat eral spinot halamic t ract [8] ; and loss of t ast e result ing f rom involvement
of t he nucleus and t ract us solit arius. Cont ralat eral hyperhydrosis and ipsilat eral
anhidrosis can also be observed in t he lat e phase of pat ient s w it h t he
Wallenberg syndrome and is likely due t o a lesion of t he sympat het ic pat hw ay
[ 182] . Hiccough has been at t ribut ed t o involvement of t he respirat ory cent ers in
t he medullary ret icular f ormat ion.
The medial medullary syndrome (Dejerine's syndrome) is less common and may
be caused by dist al at herosclerot ic vert ebral art ery occlusive disease [124,
224] . Vert ebral art ery dissect ion, dolichoect asia of t he vert ebrobasilar syst em,
or embolism are less common causes of t he medial medullary inf arct ion. The
f indings associat ed w it h t his syndrome include an ipsilat eral low er mot or neuron
paralysis of t he t ongue and cont ralat eral paralysis of t he arm and leg. The f ace
is of t en spared. An ipsilat eral lingual palsy is seen in only half of t he cases. I n
rare inst ances upbeat nyst agmus may be present [124] . A crossed mot or
hemiparesis (hemiplegia cruciat a) is an ext remely rare occurrence [23] . I n
addit ion, t here is cont ralat eral loss of t act ile, vibrat ory, and posit ion sense.
These signs are at t ribut ed t o t he involvement of t he pyramidal t ract rost ral t o
t heir decussat ion, t he f ibers and nucleus of t he hypoglossal nerve, and t he
medial lemniscus [13, 215] . As a rare occurrence, some pat ient s w it h medial
medullary inf arct s display t riparesis probably due t o a presumpt ive rost ral
decussat ion of low er ext remit y f ibers [74] ; or isolat ed acut e bilat eral t ongue
paralysis due t o exclusive and simult aneous involvement of t he hypoglossal
nerves at t he medullary t egment um [16] . The occlusion of t he vert ebral art ery
can lead t o a t ot al unilat eral hemimedullary (Babinski-Nageot t e) syndrome, w hich
is a combinat ion of t he medial and lat eral medullary syndrome. Bilat eral medial
medullary and bilat eral lat eral medullary syndromes are ext remely rare. Because
of t he separat e art erial t opography supplying t he medulla, t he simult aneous
occurrence of ischemic lesions involving t he lat eral and medial part s of t he
medulla is ext remely rare [160, 76] .
The Posterior Cerebral Artery Syndrome

The clinical pict ure of PCA t errit ory inf arct ion varies according t o t he sit e of
occlusion and t he availabilit y of collat erals. O cclusion of t he precommunal P1
segment causes midbrain, t halamic, and hemispheric inf arct ion. O cclusion of t he
PCA in t he proximal ambient segment bef ore branching in t he t halamogeniculat e
pedicle causes lat eral t halamic and hemispheral sympt oms. O cclusions may also
aff ect a single PCA branch, primarily t he calcarine art ery, or cause a large
hemispheric inf arct ion of t he PCA t errit ory. Whet her embolic, t hrombot ic, or
migrainous, part ial syndromes are t he rule. I nf arct ion in t he dist ribut ion of t he
hemispheric branches of t he PCA may produce cont ralat eral homonymous
hemianopia caused by inf arct ion of t he st riat e cort ex, t he opt ic radiat ions, or t he
lat eral geniculat e body. There is part ial or complet e macular sparing if t he
inf arct ion does not reach t he occipit al pole. The visual f ield def ect may be
limit ed t o a quadrant anopia. A superior quadrant anopia is caused by inf arct ion of
t he st riat e cort ex inf erior t o t he calcarine f issure or t he inf erior opt ic radiat ions
in t he t emporo-occipit al lobes. An inf erior quadrant anopia is t he result of an
inf arct ion of t he st riat e cort ex superior t o t he calcarine f issure or t he superior
opt ic radiat ions in t he pariet o-occipit al lobes.
More complex visual changes may occur, including f ormed or unf ormed visual
hallucinat ions, visual and color agnosias, or prosopagnosia. Finally, some
alt erat ion of sensat ion w it h PCA hemispheral inf arct ions occurs, including
parest hesiae, or alt ered posit ion, pain, and t emperat ure sensat ions. Sensory
f indings may indicat e t halamic ischemia due t o occlusion of t he precommunal or
proximal post communal segment s of t he PCA, t halamopariet al ischemia due t o
occlusion of t he more dist al PCA or it s pariet o-occipit al branches, or brainst em
ischemia caused by vascular occlusive disease in t he proximal vert ebrobasilar
art erial syst em [79] . I nf arct ion in t he dist ribut ion of t he callosal branches of t he
PCA involving t he lef t occipit al region and t he splenium of t he corpus callosum
produces alexia w it hout agraphia (pure w ord blindness), occasionally associat ed
w it h color anomia and object and phot ographic anomia [57] . I n t his syndrome,
pat ient s can w rit e, speak, and spell normally, but are unable t o read w ords and
sent ences. The abilit y t o name let t ers and numbers may be int act , but t here can
be inabilit y t o name colors, object s, and phot ographs. Right hemispheric PCA
inf arct ions may cause cont ralat eral visual f ield neglect . Amnesia may present
w it h PCA inf arct ions t hat involve t he lef t medial t emporal lobe or w hen t here are
bilat eral mesiot emporal inf arct ions [41, 72, 149, 173, 174] . I n addit ion, an
agit at ed delirium may occur w it h unilat eral or bilat eral penet rat ing mesiot emporal
inf arct ions [59] . Large inf arct ions of t he lef t post erior t emporal art ery t errit ory
may produce an anomic or t ranscort ical sensory aphasia. I nf arct ions in t he
dist ribut ion of t he penet rat ing branches of t he PCA t o t he t halamus can cause
aphasia if t he lef t pulvinar is involved, akinet ic mut ism, global amnesia, and t he
Dejerine-Roussy syndrome.
O cclusion of t he calcarine art ery may be associat ed w it h pain in t he ipsilat eral
eye [183] . Bilat eral inf arct ions in t he dist ribut ion of t he PCA may cause bilat eral
homonymous hemianopia. Bilat eral occipit al or occipit opariet al inf arct ions may
result in cort ical blindness w it h preserved pupillary ref lexes. Pat ient s of t en deny
or are unaw are of t heir blindness (Anton's syndrome). I nf arct ion in t he t errit ory
of t he hemispheric branches of t he PCA may also be accompanied by f ormed or
unf ormed visual hallucinat ions (“release hallucinat ions”) [39] , visual and color
agnosias, or prosopagnosia (agnosia f or f amiliar f aces). Apraxia of ocular
movement s is of t en present w it h bilat eral lesions. Some pat ient s w it h bilat eral
occipit al or pariet o-occipit al inf arct ions have associat ed opt ic at axia, psychic
paralysis of f ixat ion w it h inabilit y t o look t o t he peripheral f ield, and dist urbance
of visual at t ent ion and simult anagnosia (Balint 's syndrome). Proximal PCA
occlusion may simulat e MCA occlusion w hen it causes hemiparesis, hemianopsia,
hemispat ial neglect , aphasia, and sensory loss or inat t ent ion [45] . “Cort ical”
signs are probably explained by t halamic involvement .
Syndromes of Thalamic Infarction

The t halamus is t he largest subdivision of t he diencephalon. The main t halamic
blood supply originat es f rom t he post erior communicat ing art eries and t he
perimesencephalic segment of t he PCA. Thalamic inf arct ions t ypically involve one
of t he f our major vascular regions (Fig. 21-4): post erolat eral, ant erior,
paramedian, and dorsal [192] . Post erolat eral t halamic inf arct ions result f rom
occlusion of t he t halamogeniculat e branches arising f rom t he P2 segment of t he
PCA. Three common clinical syndromes may occur: pure sensory st roke,
sensorimot or st roke, and t he t halamic syndrome of Dejerine-Roussy. I n t he lat t er
syndrome, t he pat ient has cont ralat eral sensory loss t o all modalit ies, severe
dysest hesias of t he involved side
(t halamic pain), vasomot or dist urbances, t ransient cont ralat eral hemiparesis, and
choreoat het oid or ballist ic movement s. Ant erior t halamic inf arct ion result s f orm
occlusion of t he polar or t uberot halamic art ery. The main clinical manif est at ions
consist of neuropsychological dist urbances such as abulia, apat hy,
disorient at ion, lack of insight and personalit y changes, cont ralat eral emot ional-
f acial paresis, occasional hemiparesis, and visual f ield def icit s. Lef t -sided
inf arct s are associat ed w it h dysphasia; select ive impairment in semant ic memory
may be seen [191] , w hereas hemineglect and alien hand syndrome [141, 167]
may be seen primarily in pat ient s w it h right -sided lesions. Paramedian t halamic
inf arct ions result f rom occlusion of t he paramedian or t halamic and subt halamic
art eries (t halamoperf orat ing pedicle). The main clinical manif est at ions include
somnolence
or t ransient loss of consciousness, memory loss or mood dist urbances, and

vert ical gaze abnormalit ies. Paramedian t halamic inf arct s may also produce
abnormal sleep and body core t emperat ure abnormalit ies [158] ; and bilat eral
eyelid t remor on volunt ary eyelid closure [106] . Paramedian t halamic inf arct s
may be unilat eral or bilat eral, and of t en result f rom an embolic occlusion of t he
basilar apex, causing a disconnect ion bet w een t he t halamus and t he f ront al
lobes. Dorsal t halamic inf arct ions result f rom occlusion of t he post erior choroidal
art eries. These inf arct ions are charact erized by t he presence of homonymous
quadrant anopia or homonymous horizont al sect oranopias. There may also be an
asymmet ric opt okinet ic response and hemibody (f ace and arm) hypest hesia.
I nvolvement of t he pulvinar may account f or t halamic aphasia.
FI G URE 21-4 Pat t erns of t halamic inf arct ion
Movement disorders af t er t halamic inf arct s are rare and include myoclonic
dyst onia, ast erixis, post ural, act ion, and t ask-specif ic t remors [105, 115, 116,
138, 168] .
Border Zone Ischemia

During or af t er cardiac surgery or af t er an episode of severe hypot ension,
ischemia may occur in t he border zone or w at ershed areas bet w een t he major
circulat ions. Border zone ischemia is of t en explained by t he combinat ion of t w o
f requent ly int errelat ed processes: hypoperf usion and embolizat ion [15] . Border
zone ischemia may result in several charact erist ic syndromes [96] :
1. I schemia in t he border zone t errit ory of all t hree major art erial syst ems
(ant erior, middle, and PCA) may result in bilat eral pariet o-occipit al lesions.
Pat ient s develop bilat eral low er alt it udinal visual f ield def ect s; diff icult y in
judging size, dist ance, and movement ; and disorders of smoot h ocular
pursuit . O pt ic at axia or cort ical blindness may also occur.
2. I schemia bet w een t he ant erior and middle cerebral art eries (bilat eral) may
result in bibrachial cort ical sensorimot or impairment , init ially aff ect ing w hole
limbs but lat er conf ined t o t he hands and f orearms. Also, t here may be a
dist urbance of volit ional saccadic eye movement s due t o f ront al eye f ield
involvement .
3. I schemia of t he border zone t errit ory bet w een t he middle and PCA may
result in bilat eral pariet ot emporal lesions. I nit ially, t here is cort ical blindness
t hat rapidly improves but leaves a marked dyslexia, dyscalculia, dysgraphia,
and memory def ect f or verbal and nonverbal mat erial.
Unilat eral w at ershed inf arct s may occur during episodes of syst emic hypot ension
w hen t here is preexist ing ipsilat eral vascular disease causing f ocal
hypoperf usion in t he most dist al t errit ory [29] . Syncope at onset and f ocal limb
shaking are f requent and suggest acut ely low ered cerebral perf usion. Most
pat ient s have I CA occlusion or t ight st enosis w it h a hemodynamically signif icant
cardiopat hy, increased hemat ocrit , or acut e hypot ension. Embolic inf arct ion is
uncommon. I n a review of 51 pat ient s w it h sympt omat ic unilat eral w at ershed
inf arct s [29] , t hree t ypes w ere not ed:
1. Wat ershed inf arct s in t he border zone bet w een t he superf icial t errit ories of
t he middle and ant erior cerebral art eries (ant erior w at ershed inf arct ) w ere
seen in 22 pat ient s. Typically, ant erior inf arct s mainly caused crural
hemiparesis (leg great er t han arm) sparing t he f ace, associat ed in one-half
of pat ient s w it h impaired sensat ion of t he same t opography, usually of
“noncort ical” t ype (element ary modes of sensat ion). Dominant -hemisphere
lesions of t en caused t ranscort ical mot or aphasia preceded by mut ism f or 1
hour t o 1 w eek; less f requent ly, isolat ed w ord-f inding diff icult y w as not ed.
Wit h nondominant -hemisphere lesions, mood dist urbances (apat hy or
euphoria) w ere common.
2. Wat ershed inf arct s in t he border zone bet w een t he superf icial t errit ories of
t he middle and t he PCA (post erior WS inf arct s) w ere not ed in 20 pat ient s. I n
post erior inf arct s, hemianopsia w as t he most common abnormalit y, alw ays
noncongruent , and usually w it h macular sparing and predominant ly in t he
low er quadrant . “Cort ical” hemihypest hesia (t w o-point discriminat ion,
st ereognosis) w as also common, but limb w eakness w as rare. Wit h
dominant -hemisphere lesions, language dist urbances w ere common, w it h
isolat ed w ord-f inding diff icult y (anomia), t ranscort ical sensory aphasia, and,
rarely, Wernicke's aphasia. Speech disorders w ere never preceded by
mut ism, and approximat ely one-half of t he pat ient s show ed marked
depression. Wit h nondominant -hemisphere lesions, cont ralat eral hemispat ial
neglect and anosognosia w ere common.
3. Wat ershed inf arct s in t he border zone bet w een t he superf icial and deep
t errit ories of t he MCA (subcort ical w at ershed inf arct s) occurred in nine
pat ient s. Hemiparesis w as common, and approximat ely one-half had
hemisensory (usually “noncort ical”) def ect s. Language disorders (Broca's
aphasia, global aphasia, t ranscort ical mot or aphasia) w ere common w it h
dominant
hemisphere lesions, and nondominant lesions of t en had hemineglect .
I nf arct ions at t he boundary bet w een t he ACA, MCA, and post erior cerebral
art ery, ipsilat eral t o a severe st enosis or occlusion of t he I CA, result ing in
reduced blood f low t o t he w hit e mat t er of t he angular gyrus of t he inf erior
pariet al lobe, may cause an evolving nonpyramidal mot or def icit of t he hand
[ 209] .
Lacunar Infarcts
I schemic st rokes may result f rom (a) large art ery at herosclerot ic disease
result ing in st enosis or occlusion, (b) small vessel or penet rat ing art ery disease
(lacunes), (c) cardioaort ic embolism, (d) nonat herosclerot ic vasculopat hies, (e)
hypercoagulable disorders, and (f ) inf arct s of undet ermined cause. Lacuna
ref ers t o small necrot ic/ cyst ic lesions of t he brain or brainst em associat ed w it h
art erial hypert ension. As such, lacuna is a pat hologic t erm. A lacunar syndrome
is t he clinical pict ure due t o lacuna or lacune. How ever, lacunar syndromes may
be associat ed w it h nonlacunar mechanisms of inf arct ion, and may even be
mimicked by subcort ical and brainst em hemorrhages.
Lacunes are small ischemic inf arct s in t he deep regions of t he brain or brainst em
t hat range in diamet er f rom 0. 5 t o 15 mm result ing f rom occlusion of a single
perf orat ing vessel (e. g. , AChA, MCA, post erior cerebral art ery, or basilar
art ery). Lacunes usually occur in pat ient s w it h lipohyalinosis of penet rat ing
art eries or branches relat ed t o long-st anding art erial hypert ension [71, 154,
157] . Diabet es mellit us and ext racranial art erial and cardiac sources of
embolism are f ound less f requent ly. The most f requent sit es of lacunes are t he
put amen, basis pont is, t halamus, post erior limb of t he int ernal capsule, and
caudat e nucleus, in t hat order. Lacunes may also occur in t he ant erior limb of t he
int ernal capsule, subcort ical cerebral w hit e mat t er, cerebellar w hit e mat t er, and
corpus callosum. Most lacunes are asympt omat ic, and alt hough t hey generally
carry a relat ively f avorable prognosis, mult iple lacunes may lead t o pseudobulbar
palsy or dement ing st at es. I n general, most pat ient s w it h lacunar inf arct s have a
good f unct ional recovery, w it h a low er recurrence rat e and higher survival rat e
t han ot her ischemic st roke subt ypes. Short ly bef ore onset of a lacunar st roke,
TI As may occur. Associat ed headaches are inf requent .
Lacunar inf arct s represent an import ant ischemic st roke subgroup; it has been
est imat ed t hat t hey may account f or up t o 20% of st rokes. At least 20 lacunar
syndromes have been described [46] . The f our best recognized clinical
syndromes relat ed t o lacunar st rokes can be described as f ollow s:
1. Pure motor hemi paresi s or pure motor stroke is of t en due t o an int ernal
capsule, corona radiat a, or basis pont is lacune and is charact erized by a
unilat eral mot or def icit (hemiparesis or hemiplegia) involving t he f ace, arm,
and, t o a lesser ext ent , t he leg, accompanied by mild dysart hria, part icularly
at t he onset of st roke [162] . Pat ient s may have a series of preceding TI As
(capsular w arning syndrome). There should be no aphasia, apraxia, or
agnosia, and t here are no sensory, visual, or higher cort ical dist urbances.
Clinical f indings usually do not dist inguish bet w een capsular or pont ine pure
mot or hemiparesis, but t he combinat ion of dysart hria and a hist ory of
previous t ransient gait abnormalit y or vert igo f avor a pont ine locat ion [162] .
I schemic cort ical lesions may also cause pure mot or hemiparesis [107] . A
pure mot or monoparesis is seldom caused by a lacunar inf arct .
2. Pure sensory stroke, also know n as pure parest het ic st roke or pure
hemisensory st roke, is of t en due t o a lacune involving t he
vent ropost erolat eral nucleus of t he t halamus. I t is charact erized by
numbness, parest hesias, and a unilat eral hemisensory def icit involving t he
f ace, arm, t runk, and leg. Subject ive sympt oms of t en predominat e over
object ive f indings in t his syndrome. Sensory sympt oms due t o st roke of t en
produce dist al manif est at ions in t he f orm of cheiro-oral, cheiro-pedal, or
cheiro-oral-pedal syndromes [70, 112, 125] . O nly rarely are t he sensory
manif est at ions rest rict ed t o proximal body segment s [123, 113, 114] . Small
ischemic st rokes in t he int ernal capsule/ corona radiat a, subt halamus,
midbrain, or t he pariet al cort ex may also cause a pure sensory st roke [107,
193] , as may pont ine lacunes localized t o t he medial lemniscus [194] or
paramedian dorsal pons [120] . Diff erent iat ion of a pont ine pure sensory
syndrome f rom a t halamic pure sensory syndrome may be diff icult . Brainst em
(pont ine or midbrain) pure sensory st rokes of t en show a discrepancy
bet w een superf icial and deep sensat ions. I n pont ine pure sensory st roke,
vibrat ion and posit ion sense (medial lemniscal modalit ies) are of t en reduced
on t he parest het ic side, w hereas sensat ion t o pinprick and t emperat ure
(spinot halamic modalit ies) is preserved. Conversely, in cases of pure
sensory st roke involving t he t halamus, int ernal
capsule, or corona radiat a, bot h spinot halamic and medial lemniscal

modalit ies are compromised [194, 193] . Likew ise, ipsilat eral impairment of
smoot h pursuit and vest ibulo-ocular ref lex may indicat e a pont ine lesion in
pat ient s w it h hemisensory st roke [103] . A pure sensory def icit aff ect ing pain
and t emperat ure sensat ion only has been described because of a small
hemorrhage in t he dorsolat eral midbrain t hat w as limit ed t o t he dorsal
spinot halamic t ract [3, 10] .
I n a report of 21 pat ient s w it h pure sensory st roke, 11 pat ient s had t halamic
st rokes (pansensory or rest rict ed sensory loss), 7 pat ient s had lacunes or
hemorrhages in t he lent iculocapsular region or corona radiat a (abnormalit ies
of spinot halamic t ract sensat ion), 2 had pont ine t egment al st rokes (select ive
sensory loss of t he medial lemniscal t ype), and 1 had a small cort ical inf arct
(cort ical sensory loss) [112] . Hemisensory def icit s of all modalit ies w ere
usually associat ed w it h a relat ively large lacune or hemorrhage in t he lat eral
t halamus, w hereas t ract -specif ic or rest rict ed sensory changes suggest ed
very small st rokes in t he sensory pat hw ay f rom t he pons t o t he pariet al
cort ex [112] .
3. Ataxi c hemi paresi s is of t en due t o a lacune aff ect ing eit her t he cont ralat eral
post erior limb of t he int ernal capsule or t he cont ralat eral basis pont is [83,
107, 211] . How ever, af t er ext ensive invest igat ions, a diagnosis of lacunar
inf arct due t o hypert ensive small art ery disease has been f ound in only
slight ly more t han half of t he cases of at axic hemiparesis [161] . At axic
hemiparesis is charact erized by mild t o moderat e hemiparesis, predominant ly
in t he low er ext remit y, and an ipsilat eral cerebellar t ype of incoordinat ion of
t he arm and leg out of proport ion t o t he w eakness. There is usually an
ext ensor plant ar response and no dysart hria. Facial involvement is rare.
Cort ical signs or visual f ield def icit s are absent . This syndrome has also
been described w it h cont ralat eral t halamocapsular lesions, lesions of t he
cont ralat eral red nucleus, lesions of t he corona radiat a, lent if orm nucleus,
w it h superior cerebellar art ery t errit ory inf arct s, and w it h superf icial ACA
t errit ory inf arct s in t he paracent ral area.
A pat ient w it h w eakness of t he right leg and homolat eral at axia of t he arm,
caused by a subcort ical inf arct in t he area supplied by t he ACA in t he lef t
paracent ral region, show ed decreased blood f low in t he lef t lat eral f ront al
cort ex and in t he right cerebellar hemisphere (crossed cerebral–cerebellar
diaschisis) [80] . The homolat eral at axia of t he arm w as t hought t o be caused
by decreased f unct ion of t he right cerebellar hemisphere because of a lesion
of t he cort ico-pont ine-cerebellar t ract s, w hereas crural hemiparesis w as
t hought t o be due t o a lesion of t he upper part of t he corona radiat a.
Numerous report s have expanded t he spect rum of clinical syndromes and
signs associat ed w it h at axic hemiparesis. The f ollow ing are included:
hemiat axia–hypest hesia syndrome, painf ul at axic hemiparesis, hypest hesic
at axic hemiparesis, at axic hemiparesis accompanied by cont ralat eral
sensorimot or or mot or t rigeminal w eakness, dysart hria–hemiat axia, and
quadrat axic hemiparesis [5, 83, 108, 151, 161, 185] .
4. Dysarthri a–cl umsy hand syndrome is of t en due t o a lacune involving t he
dept h of t he basis pont is bet w een it s upper t hird and low er t w o-t hirds and is
charact erized by supranuclear f acial w eakness, deviat ion of t he prot ruded
t ongue, dysart hria, dysphagia, loss of f ine mot or cont rol of t he hand, and an
ext ensor plant ar response. Lacunar inf arct s in t he int ernal capsule and
cerebral peduncle may also cause t his syndrome [107] . Lacunar inf arct ions
or small hemorrhages involving t he put amen and genu of t he int ernal capsule
may cause t he dysart hria–clumsy hand syndrome associat ed w it h
micrographia [163] . Dysart hria is also a major sign in ot her lacunar
syndromes such as dysart hria–pure mot or hemiparesis, pure dysart hria,
dysart hria–f acial paresis, and dysart hria–f acial-lingual paresis (capsular
genu syndrome) [219, 220] .
These syndromes (pure mot or hemiparesis, pure sensory st roke, at axic

hemiparesis, and dysart hria–clumsy hand) have also been recognized in
associat ion w it h discret e subcort ical and brainst em hemorrhages [88] .
Cerebral Hemorrhage Syndromes

I CH is a common cause of disabilit y and deat h. I t is one of t he most deadly
st roke subt ypes account ing f or approximat ely 10% t o 15% of all st rokes [1,
226] . There are a number of et iologies of spont aneous I CH (Table 21-3) [22] .
I CH may be a complicat ion of art erial hypert ension, t rauma, int racranial
aneurysms, int racranial vascular malf ormat ions, bleeding diat heses, cerebral
amyloid angiopat hy, primary or met ast at ic brain t umors, vasculit is, ant icoagulant
t herapy, t hrombolyt ic t herapy, or t he use of illicit drugs. Brain hemorrhages
associat ed w it h cerebral venous occlusive disease, inf ect ious disorders, or
f ollow ing surgical procedure, are less f requent , but w ell recognized.
Approximat ely 80% of all hypert ensive I CHs are suprat ent orial, and 20% are
inf rat ent orial. Approximat ely one-half is relat ed t o art erial hypert ension. Art erial
hypert ension induces a necrot izing art eriopat hy (f ibrinoid degenerat ion,
lipohyalinosis) and Charcot -Bouchard microaneurysm f ormat ion. These vascular
changes have a similar anat omical dist ribut ion t o t hat of spont aneous I CH [77] .
Hypert ensive hemorrhages are more common in t he art erial t errit ories of t he
lent iculost riat es, t halamoperf orat ors, superior cerebellar, and paramedian
branches of t he basilar art ery [146] .
TABLE 21-3 Etiologies of Spontaneous Intracerebral

Hemorrhage
Arterial hypertension
Aneurysms
Saccular
Infective
Traumatic
Neoplastic
Vascular malformations
Arteriovenous malformations
Capillary telangiectasias
Cavernous malformations
Developmental venous anomalies
Bleeding diatheses
Leukemia
Thrombocytopenia (drug-induced, idiopathic
thrombocytopenic purpura)
Disseminated intravascular coagulation
Polycythemia
Hyperviscosity syndromes
Hemophilia A and B
Glanzmann thromboasthenia
Hypoprothrombinemia
Afibrinogenemia and hypofibrinogenemia
Selective factor deficiencies (V, VII, XIII)
von W illebrand disease
Genetic polymorphisms: factor XIII, alpha 1
antichymotrypsin, apolipoprotein E (E2 and E4)
Sickle cell anemia
Anticoagulant therapy (warfarin, heparin, heparinoids,
thrombin inhibitors)
Thrombolytic therapy
Aspirin and other platelet antiaggregants
Uremia
Liver transplantation
Alcohol
Cerebral amyloid angiopathy
Arteritis/Nonatherosclerotic arteriopathies
Infectious vasculitis
Multisystem vasculitis
Isolated angiitis of the central nervous system
Moyamoya disease
Drug related
Amphetamines
Methylenedioxymethamphetamine (Ecstasy)
Cocaine
Ephedrine
Pseudoephedrine
Phenylpropanolamine
Talwin–pyribenzamine
Phencyclidine
Heroin
Monoamine oxidase inhibitors
Lysergic acid diethylamide
Intracranial tumors
Primary malignant or benign
Metastatic
Cerebral venous occlusive disease
Miscellaneous
After carotid endarterectomy
After selective neurosurgical procedures
After spinal anesthesia
Postmyelography
Cold related
Lightning stroke
Heat stroke
Fat embolism
Post painful dental procedures
Protracted migraines
Methanol intoxication
Organic acidemias (propionic, methylmalonic,
isovaleric)
Snake envenomation
Scorpion sting
Rupt ure of an int racranial saccular aneurysm is a cause of I CH. I nt racerebral

hemat omas associat ed w it h int racranial aneurysms are most of t en due t o
rupt ured middle cerebral, ant erior communicat ing, or I CA aneurysms. Aneurysms
arising f rom t he MCA of t en cause hemat omas
w it hin t he ant erior t emporal lobe or insular region. Hemat omas originat ing f rom
aneurysms of t he ant erior communicat ing art ery complex or more dist al branches
of t he ACA involve t he sept um and inf erior f ront al lobe. Dist al ACA aneurysms
are more prone t o cause hemat omas of t he ant erior superior aspect of t he
corpus callosum. Hemat omas arising f rom rupt ured I CA bif urcat ion aneurysms
are usually locat ed in t he ant erior t emporal lobe or t emporal horn. Rupt ured
int racranial aneurysms may also be t he source of int ravent ricular and subdural
hemorrhages.
General Features of the Clinical Syndrome

I CH may present clinically in very much t he same w ay as an ischemic st roke, and
f or t his reason it may be clinically indist inguishable. The presence of severe
hypert ension or a bleeding diat hesis, as w ell as severe headache and vomit ing,
f avors a diagnosis of I CH. The clinical course is usually charact erized by a
nonf luct uat ing or gradually progressive det eriorat ion over minut es t o hours.
Subst ant ial hemat oma grow t h (great er t han one-t hird of baseline volume) is
f requent ly observed among pat ient s present ing w it hin 3 hours of sympt om onset
[ 37] . O bserved neurologic manif est at ions vary w it h t he locat ion, size, direct ion
of spread, and rat e of development of I CH [69] . Depending on locat ion and size,
half of t he pat ient s have headaches, nausea, and vomit ing. There may be a
variable level of alert ness. Seizures are common w it h lobar hemorrhages.
Meningeal irrit at ion is seen if t he bleeding ext ends t o t he subarachnoid space.
O pht halmoscopy may show ret inal hemorrhages.
The most common sit es involved by spont aneous I CH are t he put amen, t he lobar
subcort ical w hit e mat t er, t he t halamus, t he cerebellum, t he pons, t he caudat e
nucleus, and t he vent ricles.
Specific Signs by Location

Putaminal Hemorrhage
The put amen is t he most common sit e f or hypert ensive I CH. Approximat ely one-
t hird of all hemorrhages involve t he put amen. Hemorrhages may remain localized
t o t he put amen or enlarge t o involve adjacent st ruct ures such as t he int ernal
capsule, corona radiat a, cent rum semiovale, ext ernal capsule, claust rum,
t emporal lobe, or may rupt ure int o t he vent ricular syst em. O ne of t he larger
granules of t he lat eral lent iculost riat e art eries coursing near t he out er aspect of
t he put amen is know n as t he “art ery of cerebral hemorrhage” because of it s
f requent involvement w it h t his t ype of I CH [199] . Most put aminal hemorrhages
are lat eral (t errit ory of lat eral lent iculost riat e art eries) and remain localized t o
t he lent icular nucleus or propagat e t ow ards t he insula. The classic pict ure [94] is
charact erized by cont ralat eral hemiparesis or hemiplegia accompanied by
conjugat e gaze pref erence t o t he side of t he hemat oma. The severit y of t he
mot or def icit depends on t he ext ension int o t he post erior limb of t he int ernal
capsule. The pupils are usually spared. There may be a less severe cont ralat eral
hemisensory loss. Lef t put aminal hemorrhages may cause aphasia; right
put aminal hemorrhages cause apract agnosia, lef t visual f ield neglect , and
const ruct ional apraxia. Pat ient s w it h right put aminal hemorrhage may also
demonst rat e al l oesthesi a, in w hich a noxious st imulus on t he side of t he
hemisensory dist urbance is perceived (af t er a half -second delay) at t he
corresponding area of t he ot her (normal) side [111] . Alloest hesia is f requent ly
not ed in t he t runk and proximal limbs and seldom in t he f ace or dist al limbs.
I mpaired level of consciousness at present at ion, hydrocephalus, int ravent ricular
ext ension, and large hemat oma size are of t en predict ors of poor f unct ional
out come or deat h [61, 217, 218] .
Chung et al, in a st udy of 215 pat ient s, classif ied put aminal/ st riat ocapsular
hemorrhages int o f ive regional t ypes and one massive t ype [48] . The
st riat ocapsular region encompassed t he lent icular nucleus, caudat e nucleus,
int ernal capsule, ext ernal capsule, and subinsular area.
1. Anteri or type (11%). These small hemat omas occurred in t he t errit ory of t he
Heubner art ery and involved t he caudat e nucleus (head and body). Rupt ure
int o t he ant erior horn of t he lat eral vent ricle w as a f requent f inding. Major
clinical sympt oms and signs w ere severe headache and meningismus
(mimicking SAH), t ransient mild hemiparesis, and behavioral abnormalit ies
including conf usion, abulia, and perseverat ion. O ut come w as usually very
f avorable.
2. Mi ddl e type (7%). These moderat e size hemat omas occurred in t he t errit ory
of t he medial lent iculost riat e art eries and involved t he globus pallidus and
middle port ions of t he medial put amen. Vent ricular rupt ure w as uncommon.
The major clinical signs w ere t ransient conjugat e gaze paresis t ow ards t he
sit e of t he hemat oma and cont ralat eral hemimot or/ hemisensory def icit s. The
clinical course w as f avorable in half of t he pat ient s w ho ret urned t o normal
act ivit ies.
3. Posteromedi al type (4%). These very small hemat omas occurred in t he

t errit ory of t he AChA and involved t he ant erior half of t he post erior limb of
t he int ernal capsule. The major clinical signs w ere dysart hria and
cont ralat eral mot or/ sensory def icit s. A “lacunar syndrome” t ype of
present at ion w as not uncommon. The out come w as excellent .
4. Posterol ateral type (33%). These moderat e t o large size hemat omas
occurred in t he t errit ory of t he post eromedial branches of t he lat eral
lent iculost riat e art eries, and involved t he post erior half of t he put amen and
post erior limb of t he int ernal capsule. Major clinical f eat ures w ere impaired
consciousness, cont ralat eral hemiparesis or hemisensory def icit s, language
dysf unct ion, neglect or anosognosia. Clinical course w as f air t o poor in 75%
of cases, and excellent in t he remaining 25%.
5. Lateral type (21%). These of t en large ellipt ically shaped hemat omas
occurred in t he t errit ory of t he lat eral branches of t he lat eral lent iculost riat e
art eries involving t he region bet w een t he ext ernal capsule and t he insular
cort ex. Major clinical f eat ures w ere variable levels of alert ness and
conjugat e gaze paresis in t he acut e phase. O t her clinical signs included
hemiparesis, language dysf unct ion, or anosognosia. The prognosis w as in
general excellent except in cases of large hemat omas.
6. Massi ve (24%). These very large hemat omas occupied t he ent ire
st riat ocapsular area; t he caudat e nucleus and ant erior limb of t he int ernal
capsule w ere occasionally spared. This t ype of hemat oma w as commonly
associat ed w it h vent ricular rupt ure and hydrocephalus. Pat ient s w ere of t en
unconscious, w it h evidence of ocular dysmot ilit y including “w rong-w ay eye
deviat ion, ” and signs indicat ive of subf alcine or t ranst ent orial herniat ion.
Case f at alit y w as 81%.
Lobar Hemorrhage
Lobar I CH, def ined as suprat ent orial hemispheric parenchymal bleeding locat ed
out side t he deep nuclear st ruct ures, account s f or 7% t o 32% of nont raumat ic
int racranial bleeding [199] . Lobar hemorrhages originat e f rom t he gray-w hit e
mat t er junct ion and ext end int o t he adjacent w hit e mat t er. Lobar hemorrhages
arise f rom a variet y of sources, including cerebral art eriovenous malf ormat ions,
int racranial aneurysms, bleeding diat hesis, primary or met ast at ic brain t umors,
cort ical or dural venous sinus t hrombosis, cerebral amyloid angiopat hy,
sympat homimet ic drugs, and art erial hypert ension [146] .
Front al lobe hemorrhages [181] may result in cont ralat eral hemiparesis and
abulia; conjugat e deviat ion of t he eyes t ow ard t he side of t he hemat oma may
occur. Bif ront al headache (maximum ipsilat eral) is f requent ly report ed.
Pariet al lobe hemorrhages [181] may cause cont ralat eral hemisensory loss and
neglect of t he cont ralat eral visual f ield. These hemat omas may also cause
variable degrees of cont ralat eral homonymous hemianopsia, mild hemiparesis,
and anosognosia.
Dominant t emporal lobe hemorrhages [181] may cause Wernicke's aphasia.
Hemat omas aff ect ing t he lef t t emporopariet al area can also result in conduct ion
or global aphasia. Temporal lobe hemorrhages may also cause visual f ield
def ect s, headache around or ant erior t o t he ipsilat eral ear, and, occasionally,
agit at ed delirium.
O ccipit al lobe hemorrhages [181] are charact erized by ipsilat eral orbit al pain
and cont ralat eral homonymous hemianopsia.
Focal seizures w it h secondary generalizat ion may occur during t he acut e phase
of a lobar hemat oma. Large lobar hemat omas may also cause hydrocephalus
[ 170, 222] .
Thalamic Hemorrhage
Hemorrhages in t he t halamus are usually hypert ensive but may be due t o
underlying st ruct ural lesions [133] . Thalamic hemorrhage may be conf ined t o t he
t halamus or ext end lat erally t o involve t he int ernal capsule, inf eromedially t o
compromise t he subt halamus and midbrain, or medially t o involve t he t hird
vent ricle. Unlike w hat is observed w it h ot her t ypes of int racranial hemat omas,
vent ricular ext ension is of t en compat ible w it h good clinical out comes [135, 237] .
Clinical f eat ures of t halamic hemorrhages vary according t o t he int rat halamic
locat ion of t he bleed and t he bleeding source [47] . The classic pict ure of
t halamic hemorrhage [69] is charact erized by cont ralat eral pansensory loss and
oculomot or abnormalit ies including impaired vert ical gaze. Hemiparesis develops
if t he int ernal capsule becomes involved. Lef t t halamic hemorrhages can cause
t ransient aphasia, w hereas right t halamic hemat omas may result in visuospat ial
abnormalit ies, anosognosia, and arm levit at ion [215] . Compromise of t he
ascending ret icular act ivat ing syst em may account f or decreased level of
consciousness and hypersomnolence. I nf eromedial ext ension account s f or
rest rict ion of vert ical gaze, convergence-ret ract ion nyst agmoid movement s,
pupillary light -near dissociat ion, and disconjugat e gaze w it h impaired abduct ion
of one or bot h eyes (pseudo–sixt h nerve palsy). The eyes
may become t onically deviat ed dow nw ard and slight ly abduct ed. They may be
t onically deviat ed aw ay f rom t he t halamic hemat oma (“w rong-w ay eyes”), or
t here may be a conjugat e gaze deviat ion, as seen in put aminal hemorrhages. The
init ial neurologic syndrome does not discriminat e inf arct s f rom t halamic
hemorrhages [201] .
Findings are exemplif ied by a st udy t hat described 50 pat ient s w it h t halamic
hemorrhages [228] . Seven pat ient s had small bleeds (<8 mm) and present ed
w it h eit her t ransient hemiparesis and numbness or headache w it h papilledema.
All t hese pat ient s recovered. Tw ent y-f our pat ient s had larger hemorrhages (9–30
mm) but no vent ricular blood and present ed w it h hemiparesis. Ninet een pat ient s
had large bleeds (>30 mm) w it h int ravent ricular hemorrhage, impaired
consciousness, hemiparesis, headache, pupillary abnormalit ies (smaller pupil
ipsilat eral t o bleed), and vert ical gaze impairment . All t he pat ient s w it h large
hemorrhages died.
O t hers [109] have classif ied small t halamic hemorrhages (< cm) int o f our t ypes
according t o t he localizat ion:
1. Anterol ateral type. These pat ient s had mild “pref ront al” signs (e. g. , impaired
verbal memory and inat t ent ion) and mild sensory and mot or impairment .
2. Posterol ateral type. These pat ient s had severe mot or and sensory disabilit y
and ocular abnormalit ies (miosis, loss of light ref lex, upw ard gaze palsy).
They had t he poorest prognosis of pat ient s w it h small t halamic hemorrhages,
w it h persist ent hemiparesis or sensory loss in most .
3. Medi al type. These pat ient s had dist urbed consciousness in t he acut e st age
f ollow ed by impaired “pref ront al” signs (e. g. , decreased spont aneit y,
memory impairment ) of long durat ion.
4. Dorsal type. These pat ient s present ed w it h “pariet o-occipit al” signs (e. g. ,
aphasia w it h lef t -sided lesions, t opographic memory dist urbances w it h right -
sided lesions).
A syndrome of posteri or t halamic hemorrhage has been described [95] and

consist s of saccadic hypomet ria aw ay f rom t he side of t he lesion (due t o
involvement of f ibers f rom t he f ront al eye f ields t hat pass near t he dorsal
t halamus on t heir w ay t o t he superior colliculus and pret ect al nuclei), def ect ive
smoot h ocular pursuit t ow ard t he lesion w it h corresponding opt icokinet ic
abnormalit ies, mild ipsilat eral pt osis and miosis (due t o associat ed ipsilat eral
hypot halamic involvement ), unilat eral sensory “t halamic” neglect , cont ralat eral
sensorimot or hemiparesis, and f orced horizont al gaze t ow ard t he lesion.
I n a st udy of 175 pat ient s, t halamic hemorrhages w ere classif ied int o f our
regional t ypes and one global t ype [47] :
1. Anteri or type (7%). This t ype occurred in t he t errit ory of t he t uberot halamic
art eries and of t en rupt ured int o t he ant erior horn of t he lat eral vent ricle. The
major clinical signs w ere acut e behavioral abnormalit ies and t he clinical
course w as usually benign.
2. Posteromedi al type (14%). This t ype occurred in t he t errit ory of t he
t halamic–subt halamic paramedian art eries. The hemat omas of t en rupt ured
int o t he t hird vent ricle, causing marked hydrocephalus, and of t en ext ended
mediocaudally, involving t he mesencephalon. Mesencephalic involvement w as
associat ed w it h poor out come.
3. Posterol ateral type (44%). This t ype occurred in t he t errit ory of t he
t halamogeniculat e art eries and w as charact erized by large hemat omas,
rupt ure int o t he post erior horn of t he lat eral vent ricle, and f requent ext ension
int o t he post erior limb of t he int ernal capsule. Clinical signs included marked
sensory and mot or f indings, hemineglect in right -sided hemat omas, and
language abnormalit ies in lef t -sided lesions. Case f at alit y w as high (35%)
and result ed in permanent neurologic sequelae f requent ly.
4. Dorsal type (18%). These occurred in t he t errit ory of t he post erior choroidal
art eries. Sensory and mot or signs w ere common and many w ere init ially
misdiagnosed as having lacunar inf arct s. The prognosis w as excellent .
5. G l obal type (18%). These occupied t he ent ire area of t he t halamus and w ere
clinically similar t o t he post erolat eral t ype w it h t he presence of severe
sensory and mot or signs. This t ype of t halamic hemorrhage is commonly
associat ed w it h hydrocephalus, mass eff ect , and a poor prognosis. These
pat ient s are of t en st uporous or comat ose, displaying decerebrat e post uring,
upw ard gaze paralysis, and small but react ive pupils. Case f at alit y w as 81%.
Cerebellar Hemorrhage
Cerebellar hemat omas account f or 10% of spont aneous I CH. Primary cerebellar
hemorrhage is t he commonest cause of nont raumat ic cerebellar hemorrhage.
Clinical present at ion may be acut e, subacut e, or chronic [34, 89, 179, 202] .
Variat ions in locat ion, size, and development of t he hemat oma; brainst em
compression; f ourt h vent ricular penet rat ion; and development of hydrocephalus
result in
variat ions in t he mode of present at ion of cerebellar hemorrhage. A massive

hemorrhage may lead t o f oraminal herniat ion or upw ard t ent orial herniat ion, or
local brainst em compression w it h irreversible damage t o vit al st ruct ures.
Hypert ensive cerebellar hemorrhages most f requent ly occur in t he region of t he
dent at e nucleus on eit her side as a consequence of a rupt ure of a dist al branch
of t he superior cerebellar art ery due t o necrot izing hypert ensive art eriopat hy.
Less of t en, t he epicent er of a cerebellar hemat oma is in t he vermis; t hese
hemorrhages seen in t he younger age group may be relat ed t o vascular
malf ormat ions and are almost alw ays associat ed w it h f ourt h vent ricular
hemorrhages.
Pat ient s w it h acut e cerebellar hemorrhage present w it h sudden occipit al or
f ront al headache, dizziness, vert igo, nausea, repeat ed vomit ing, and inabilit y t o
st and or w alk. Truncal or limb at axia, ipsilat eral gaze palsy, and small react ive
pupils are common f indings. Horizont al gaze paresis, paret ic nyst agmus, and
f acial w eakness are also f requent . I psilat eral horizont al gaze paresis and
peripheral f acial palsy are indicat ive of pont ine compression and may herald
f urt her clinical det eriorat ion. Frank hemiparesis is absent , alt hough variable
degrees of hemiparesis may be seen. O cular bobbing (rapid movement s of t he
eyes in a dow nw ard direct ion and a slow rise upw ards) and skew deviat ion may
be present . The classic t riad of sympt oms include appendicular at axia,
peripheral f acial paresis, and ipsilat eral gaze palsy, but not all pat ient s present
such a pict ure. Those w it h small (usually <-cm diamet er) cerebellar hemat omas
may present only w it h vomit ing and w it h no headaches, gait inst abilit y, or limb
at axia.
Pontine Hemorrhage
Pont ine hemorrhages account f or approximat ely 10% of spont aneous I CHs.
Primary pont ine hemorrhages usually arise f rom rupt ured paramedian art erioles,
and of t en begin at t he midlevel of t he pons near t he junct ion of t he basis pont is
and t egment um. Signs and sympt oms depend on size, locat ion, and presence or
absence of vent ricular rupt ure or hydrocephalus [230] . “Part ial” pont ine
hemat oma syndromes are increasingly recognized. G ot o et al. [84] classif ied
t hese hemorrhages as t egment al and t egment obasilar. Massive pont ine
hemorrhages involve t he w hole pons, compressing t he f ourt h vent ricle, causing
obst ruct ive hydrocephalus [84] . Massive pont ine hemorrhages cause coma,
decerebrat e rigidit y, quadriparesis, hypert hermia, t achycardia, absent corneal
ref lexes, absent horizont al eye movement s, and miot ic but react ive pupils.
O cular bobbing may be present . An acut e locked-in syndrome may occur, but
of t en t hese lesions symmet rically dissect t he pons, dest roying t he more dorsal
st ruct ures. Coma, absent oculocephalic ref lexes, absent corneal ref lexes, lack of
mot or responses, t achycardia, acut e hydrocephalus, and int ravent ricular
hemorrhage are predict ors of very poor out come [230] . Pont ine hemorrhages are
rarely associat ed w it h bilat eral deaf ness due t o compromise of t he vent ral
acoust ic st riae decussat ing in t he t rapezoid body [65] .
Primary pont ine hemorrhages have been divided int o t hree clinical t ypes [134] :
1. Cl assi c type (60%). There is severe pont ine dest ruct ion w it h quadriparesis,
coma, hypert hermia, t achycardia, and deat h.
2. Hemi ponti ne syndrome (20%). The hemat oma involves bot h t he basis pont is
and pont ine t egment um unilat erally and manif est s by hemiparesis, preserved
consciousness, skew deviat ion, unilat eral absent corneal ref lex, dysart hria,
f acial nerve palsy, cont ralat eral ext remit y and ipsilat eral f acial sensory
changes, and survival w it h f unct ional recovery.
3. Dorsol ateral tegmental syndrome (20%). This syndrome manif est s by gaze
paresis or ipsilat eral abducens nerve palsy (or bot h), skew deviat ion,
unilat eral absent corneal ref lex, unilat eral f acial nerve palsy, cont ralat eral
ext remit y and ipsilat eral f acial sensory loss, dysart hria, mot or sparing,
preserved consciousness, occasional gait or limb at axia, and survival w it h
f unct ional recovery.
O t hers have classif ied primary pont ine hemorrhage int o f our t ypes based on t he
pont ine region involved and CT scan f eat ures: basal t egment al, bilat eral
t egment al, massive, and small unilat eral t egment al [49] .
Caudate Hemorrhage
Hemorrhages in t he region of t he caudat e nucleus result f rom rupt ure of
Heubner's art ery or branches of t he medial lent iculost riat e art eries. Caudat e
hemorrhages cause headache, vomit ing, meningeal irrit at ion w it h neck st iff ness,
conf usion, and behavioral changes w it h decreased short -t erm memory [200] .
O t her variable f indings include a t ransient cont ralat eral conjugat e gaze paresis,
cont ralat eral hemiparesis, t ransient hemisensory def icit s, and, rarely, an
ipsilat eral Horner syndrome [200] .
M esencephalic Hemorrhage
Hemorrhage w it hin t he mesencephalon [227] of t en present s w it h headache and
vomit ing f ollow ed by loss of consciousness. Unequal pupils, w hich are unreact ive
t o light but ret ain t he near ref lex, are
common, as is impairment of conjugat e upgaze. Parti al dorsal mesencephal i c

hemorrhages may cause a dorsal mesencephalic (Parinaud's) syndrome (w it h
rost ral t ect al plat e bleed), a vert ical gaze palsy, skew deviat ion, and bilat eral
Horner syndrome (w it h unilat eral superior colliculus bleed), as w ell as bilat eral
t rochlear nerve palsies, unilat eral Horner syndrome, and at axia (w it h hemorrhage
in t he caudal t ect al plat e) [142, 186] .
Lateral Tegmental Brainstem Hemorrhage

Lat eral t egment al pont omesencephalic hemorrhages result in a clinically unif orm
syndrome [42] charact erized by small react ive pupils, ipsilat eral conjugat e gaze
palsy, ipsilat eral int ernuclear opht halmoplegia, cont ralat eral hemiparesis,
cont ralat eral sensory def icit s, and ipsilat eral at axia. O t her variable f indings
include alt ered vert ical gaze, skew deviat ion, ocular bobbing, decreased hearing,
dysart hria, dysphagia, decreased ipsilat eral f acial sensat ion or absent corneal
ref lex, and bilat eral pt osis. Ast asia has been described w it h t he involvement of
t he pedunculopont ine nucleus, in t he region of t he mesencephalic locomot or
cent er [142] . A crossed oro-crural syndrome has been report ed associat ed w it h
t he involvement of t he rost ral spinal t rigeminal nucleus and t he lat eral aspect of
t he spinot halamic t ract in a case of a small lat eral pont ine t egment al hemorrhage
[ 50] .
M edullary Hemorrhage
Primary medullary hemorrhage is ext remely uncommon and present s w it h a
charact erist ic syndrome of sudden onset of headache and vert igo w it h neurologic
signs t hat correspond t o various combinat ions of medial and lat eral medullary
involvement [12, 19] . The most f requent sympt oms at onset include vert igo,
sensory sympt oms, and dysphagia. Present ing signs include palat al w eakness,
nyst agmus, hypoglossal palsy, cerebellar at axia, and limb w eakness.
Internal Capsular Hemorrhage

Small hemorrhages arising in t he genu or post erior limb of t he int ernal capsule
may cause a pure mot or hemiparesis or a combined sensorimot or syndrome
[ 126] . I n rare inst ances, paraparesis due t o bilat eral hemorrhages involving t he
post erior limb of t he int ernal capsule have been described [205] .
Intraventricular Hemorrhages
I nt ravent ricular hemorrhages most commonly result f rom secondary ext ension
int o t he vent ricular syst em of a hypert ensive parenchymal hemat oma. Primary
int ravent ricular hemorrhages are rare. Clinical f eat ures include sudden onset of
headache, nausea, vomit ing, impaired consciousness, memory dist urbance, and
nuchal rigidit y. There is usually no f ocal impairment of brain f unct ion. Primary
int ravent ricular hemorrhages in adult s have been at t ribut ed t o rupt ured
int racranial saccular aneurysms, t umors (papillomas) or art eriovenous
malf ormat ion of t he vent ricle or choroid plexus, bleeding diat hesis, and art erial
hypert ension associat ed w it h bilat eral I CA occlusions. I n neonat es,
int ravent ricular hemorrhage usually result s f rom disproport ion of t he f et al head,
t rauma, or “germinal mat rix hemorrhages” as a result of prolonged anoxia w it h
premat urit y as a predisposing condit ion [17, 199] .
Syndromes Related to Cerebral Aneurysms

Three t o six million people in t he Unit ed St at es have an int racranial aneurysm
[ 152] . The prevalence of int racranial saccular aneurysms has been est imat ed t o
be 9. 6 per 100, 000 people [169] . Peak incidence is in t he sixt h decade of lif e;
int racranial aneurysms are rare in children and adolescent s. O ver 85% of
int racranial aneurysms involve t he ant erior segment s (int ernal carot id art eries
and branches) of t he circle of Willis, and 15% t he vert ebrobasilar circulat ion,
part icularly at t he basilar apex and origin of t he post erior inf erior cerebellar
art eries. Aneurysms are mult iple in approximat ely 15% t o 20% of cases,
part icularly involving mirror locat ions, such as bilat eral MCA aneurysms.
I nt racranial aneurysms arise f rom bif urcat ions of major int racranial art eries.
Most are f ound at (a) t he junct ion of t he ant erior communicat ing art ery w it h t he
ACA [204] , (b) t he junct ion of t he I CA and t he post erior communicat ing art ery,
and (c) t he main t runk of t he MCA. Pediat ric int racranial aneurysms on t he ot her
hand are more common in boys, are of t en large or giant , rarely mult iple, and
most of t en involve t he dist al I CA or post erior circulat ion; post erior
communicat ing art ery aneurysms are rare (4%) in t his segment of t he populat ion.
Aneurysms t hat rupt ure are usually more t han 7 mm in diamet er. “Arbit rary” lines
have been proposed w it h recommendat ions f or conservat ive management (due t o
low est -risk), f or unrupt ured aneurysms less t han 7 mm in diamet er, in t he
ant erior circulat ion (I CA, ACA, MCA or ant erior communicat ing art ery) [101] .
O nce an aneurysm reaches “giant ” proport ions (≥2. 5 cm), it of t en behaves like a
space-occupying lesion [101] , alt hough TI As and CI due t o dist al embolizat ion
have been report ed [164, 176] .
Clinical manif est at ions of unrupt ured aneurysms depend on t heir anat omic
posit ion, size, and project ion. A discussion of some aneurysmal syndromes
f ollow s.
Intracavernous Aneurysms of the Internal Carotid

Artery
Aneurysms arising f rom t he I CA in t he region of t he cavernous sinus may rupt ure,
causing a carot id-cavernous f ist ula, or expand, causing regional syndromes.
They occur especially in middle-aged w omen.
Ruptured Aneurysm: Carotid-Cavernous Fistula

When sympt omat ic, t his lesion is associat ed w it h t he f ollow ing:
1. O cular pain
2. Pulsat ing exopht halmos (unilat eral or bilat eral)
3. Cephalic or ocular bruit , w hich can be diminished by digit al carot id
compression in t he neck
4. Chemosis and redness of t he conjunct iva
5. Diplopia, caused eit her by cranial nerve palsy or mechanical rest rict ion of
t he globe (abducens palsy is t he most common cause)
6. Decreased visual acuit y due t o pressure on t he opt ic nerve, glaucoma, or
ret inal and opt ic nerve hypoxia
Unruptured Aneurysm
When sympt omat ic, unrupt ured int racavernous I CA aneurysms are charact erized
by t he f ollow ing:
1. O cular pain
2. Abducens, oculomot or, or t rochlear nerve palsies (in decreasing f requency)
w it h a small pupil due t o oculosympat het ic dysf unct ion
3. Pain and numbness in t he dist ribut ion of t he opht halmic division of t he
t rigeminal nerve; occasionally, all t hree divisions may be aff ect ed
4. Bilat eral opht halmoplegia (rare)
I f t here is ant erior ext ension of t he aneurysm, t he pat ient may have
exopht halmos, chemosis, or opt ic at rophy. I f t here is post erior ext ension of t he
aneurysm, t he pat ient may have deaf ness or f acial palsy.
Posterior Communicating Artery Aneurysms

The clinical dist inct ion bet w een I CA and post erior communicat ing art ery
aneurysms can be exceedingly diff icult [198] . Classically, unrupt ured aneurysms
of t he post erior communicat ing art ery may present w it h headache, ocular pain,
or oculomot or palsy w it h pupillary involvement . I f rupt ure occurs, compromise of
t he t rochlear, abducens, and opht halmic division of t he t rigeminal nerve may be
present .
Middle Cerebral Artery Aneurysms

MCA aneurysms lack a w ell-def ined clinical syndrome [73] . Because t hese
aneurysms are lodged in t he Sylvian f issure, int racerebral hemat oma is more
common t han w it h int racranial aneurysms at ot her sit es. The f ollow ing may be
seen:
1. Headache
2. Seizures, eit her part ial seizures w it h element ary sympt omat ology, complex
part ial seizures, or generalized t onic-clonic seizures; an increased
occurrence of right -sided aneurysms in pat ient s w it h “uncinat e” f it s
3. Aphasia
4. Transient sensorimot or def icit s
5. Homonymous f ield def ect s
Vertebrobasilar Artery Aneurysms

Vert ebrobasilar art ery aneurysms may arise in t he basilar, superior cerebellar,
ant erior inf erior cerebellar, vert ebral, post erior inf erior cerebellar, or post erior
cerebral art ery, in t hat order of f requency. Unrupt ured basilar art ery aneurysms
may present w it h t he f ollow ing:
1. Vert ebrobasilar TI As
2. Cerebellopont ine angle syndrome
3. Alt ernat ing hemiplegia w it h cranial nerve palsies
4. At axia
5. At ypical f acial pain
6. Abducens or f acial palsies
7. O culomot or palsy
8. Nonhemorrhagic t halamic inf arct ions
Subarachnoid Hemorrhage
SAH can be eit her primary, due t o blood invading t he subarachnoid space f rom a
rupt ured art ery or vein, or secondary, caused by an I CH leaking int o t he
vent ricular syst em and subarachnoid space af t er dissect ion t hrough t he brain
subst ance. Aneurysmal SAH is an import ant cause of mort alit y and serious
morbidit y, account ing f or approximat ely 5% t o 10% of all st rokes. I n Nort h
America, if t rauma is excluded, t he primary cause of SAH is rupt ure of an
int racranial aneurysm [88] . I n t he Unit ed St at es, rupt ure of an int racranial
aneurysm aff ect s an est imat ed 26, 000 t o 30, 000 people every year.
I nt racranial aneurysms commonly rupt ure near t he f undus. Blood ext ends int o t he
subarachnoid space, somet imes int o t he brain parenchyma, vent ricles, and rarely
int o t he subdural space. Less common causes of nont raumat ic SAH include blood
dyscrasias; cerebral amyloid angiopat hy; primary, met ast at ic, or meningeal
neoplasms; vasculit is; drug abuse; cerebral venous occlusive disease; bact erial
meningit is; spinal cord vascular malf ormat ions; and spinal cord t umors. I n some
cases of spont aneous SAH, no et iology can be f ound even at aut opsy.
Premoni tory symptoms occur in a signif icant proport ion of cases. The most
common premonit ory sympt om is headache t hat may or may not be associat ed
w it h a f ocal neurologic def icit ; at least one-t hird of pat ient s w it h aneurysmal SAH
have a w arning leak, know n as a senti nel hemorrhage. An aneurysm should be
suspect ed w hen t he f ollow ing occur:
1. Lat e onset of migraine-like headache w it h no f amily hist ory of migraine

2. Change in t he headache pat t ern in a know n migraineur
3. Severe abrupt localized and persist ent headache described as “w orst
headache”
4. Migrainous headaches ref ract ory t o convent ional t herapy
O t her premonit ory sympt oms may include episodes of neck st iff ness, diplopia,
nausea, and phot ophobia. Hemorrhage int o t he subarachnoid space is heralded
by t he development of abrupt and excruciat ing headaches of t en described as t he
“w orst headaches, ” nausea, vomit ing, and neck st iff ness. Headache occurs in
85% t o 95% of pat ient s. Many variat ions t o t he clinical pict ure occur, depending
on t he severit y of t he hemorrhage, t he presence of an associat ed hemat oma, t he
occurrence of cerebral vasospasm, or t he development of hydrocephalus,
increased int racranial pressure, or t he pat ient being hyponat remic. Aneurysmal
SAH is a medical emergency. Errors and delays in diagnosis are not inf requent .
The clinical diagnosis of SAH is det ermined f rom t he sympt omat ology and
verif ied by cranial CT scan or lumbar punct ure and by pan-cerebral angiography.
A CT scan obt ained in t he f irst 24 hours is posit ive in more t han 90% of cases. I f
t he CT scan is negat ive, a lumbar punct ure should alw ays be perf ormed, usually
conf irming t he diagnosis. I mproper evaluat ion of t he result s of cerebrospinal f luid
(CSF) can lead t o uncomf ort able sit uat ions. Eryt hrocyt es in t he CSF t hat do not
decrease in subsequent t ubes (bet w een t he f irst and last t ube), accompanied by
a pink-t inged (w it hin 4–5 hours) or yellow -t inged xant hochromic (>6 hours)
supernat ant , an elevat ed prot ein level, and increased pressure are t ypical CSF
f indings. CSF glucose is normal or may be slight ly decreased [221] . I f t he
diagnosis of SAH is est ablished, t he next st ep is t o delineat e t he abnormal
anat omic sit e t hat bled. Pan-cerebral angiography remains t he def init ive met hod
f or t his purpose. How ever, approximat ely 20% of angiograms are negat ive; a
second st udy yields t he correct diagnosis in approximat ely 1% t o 2% of cases.
MRI may be helpf ul in diff erent iat ing t he causes of SAH f rom lesions ot her t han
aneurysms. Magnet ic resonance angiography (MRA) does not have enough
sensit ivit y t o supplant angiography, and is current ly used as a screening met hod
f or asympt omat ic pat ient s. Anecdot al evidence suggest s t hat if t he clinical
suspicion f or SAH is st rong, a pan-cerebral angiogram is w arrant ed, even in
cases of a negat ive good qualit y CT scan and a negat ive lumbar punct ure (LP).
The clinical present at ion of SAH is of t en abrupt , w it h t he onset of severe
headache, phot ophobia, nausea, vomit ing, meningismus, and in many inst ances
t ransient unconsciousness cranial nerve palsies and f ocal neurologic def icit s.
Transient loss of consciousness may occur as a result of an abrupt rise in
int racranial pressure. A signif icant number of pat ient s w it h aneurysmal SAH do
not survive t o receive medical at t ent ion. Seizures, eit her f ocal or generalized,
may occur. At t he t ime of SAH, seizures may be diff icult t o diff erent iat e f rom
ext ensor post uring secondary t o increased int racranial pressure. Pat ient s may
also complain of phot ophobia, phonophobia, severe neck st iff ness or backache.
O t her signs of SAH include let hargy, vert igo, abducens, or oculomot or nerve
palsy, visual f ield cut s, paresis or parest hesias.
Several scales (Table 21-4) have been developed t o predict prognosis and assist
in examining response t o t reat ment , but t hey are subject t o int erobserver
variabilit y [180, 184, 208, 214] .
Meni ngi smus, w it h nuchal rigidit y and Kernig sign, is a common sign, but it may
be absent in one-t hird of t he cases. The opht halmoscopic f indings may include
papilledema and vit reous, subhyaloid, or preret inal hemorrhage. The syndrome of
vit reous hemorrhage in associat ion w it h any f orm of int racranial or SAH is know n
as Terson syndrome [ 190] . Pt osis or diplopia is most f requent ly caused by
oculomot or palsy secondary t o hemorrhage f rom an int ernal carot id or post erior
communicat ing art ery aneurysm. O culomot or palsy may also result f rom a
rupt ured aneurysm of t he carot id bif urcat ion, t he post erior cerebral art ery, t he
t ip of t he basilar art ery, or t he superior cerebellar art ery or f rom uncal
herniat ion. Unilat eral or bilat eral
abducens palsies may ref lect increased int racranial pressure and t heref ore lack
localizing value. Visual f ield def ect s or sudden loss of vision may occur w hen an
aneurysm rupt ures near t he visual pat hw ays. The presence of ot her f ocal
f indings, such as aphasia, hemiparesis, sensory impairment , and abnormal
ref lexes, depends on t he locat ion of t he aneurysm, f ocal collect ion of blood, or
complicat ing cerebral ischemia.
TABLE 21-4 Clinical Grading Scales in a

Subarachnoid Hemorrhage
Cooperative World Federation of

Grade Aneurysm Study Neurologic Surgeons
Scale Scale
Glasgow Coma Scale

I Symptom-free score 15: no headache
or focal signs
Glasgow Coma Scale

Mildly ill, alert, and
score 15: headache,
II responsive,
nuchal rigidity, no focal
headache present
signs
Glasgow Coma Scale

score 13–14: can have
III Moderately ill
headache, nuchal
rigidity, no focal signs
Lethargic, Glasgow Coma Scale
IV headache, no focal score 13–14: can have
signs headache, nuchal
rigidity, or focal signs
Glasgow Coma Scale

Alert, focal signs score 9–12: can have
present headache, nuchal
Glasgow Coma Scale

score 8 or less: can
V Severely ill
have headache, nuchal
Stuporous, no focal
signs

Drowsy, major focal
signs present
Grade Hunt-Hess Scale Botterell et al. Scale
Conscious with or
Asymptomatic or without signs of bleeding
I
mild headache in the subarachnoid
space
Moderate to severe
Drowsy, without
headache, nuchal
II significant neurologic
rigidity, can have
deficit
oculomotor palsy
Confusion,
Drowsy, with significant
III drowsiness, or mild neurologic deficit
focal signs
Major neurologic deficit,

Stupor or deteriorating, or older
IV
hemiparesis with preexisting
cerebrovascular disease
Coma, moribund Moribund or near

V appearance, or moribund, failing vital
extensor posturing centers, extensor rigidity
The eff ect of SAH on hypot halamic f unct ion may result in lif e-t hreat ening cardiac
arrhyt hmias, myocardial inf arct ion, severe hypert ension, “neurogenic st unned
myocardium, ” neurogenic pulmonary edema, or hyponat remia w it h cent ral salt -
w ast ing syndrome or inappropriat e secret ion of ant idiuret ic hormone (SI ADH).
Pat ient s w it h cent ral salt w ast ing have hyponat remia and hypernat riuria but
decreased blood volume. I f hyponat remia occurs as a consequence of t rue
SI ADH, pat ient s have an expanded blood volume. Poor clinical grade (Hunt -Hess
scale) and hydrocephalus are independent risk f act ors f or t he development of
hyponat remia. A t ransient rise in blood pressure and mild elevat ion of
t emperat ure can also be present .
I ncreased int racranial pressure result s f rom ext ensive SAH, a large parenchymal
hemat oma, delayed cerebral ischemia secondary t o cerebral vasospasm, brain
edema, or hydrocephalus. Clinical det eriorat ion f ollow ing SAH may ref lect
rebleeding, development of hydrocephalus, delayed cerebral ischemia secondary
t o cerebral vasospasm, or syst emic complicat ions. Rebleeding occurs w it hin 2
w eeks of t he init ial hemorrhage and is maximum on t he day of t he init ial
hemorrhage. Rebleeding should be suspect ed w hen t here is f urt her alt erat ion of
alert ness, increasing headaches, w orsening neurologic dysf unct ion, or
unexplained f ever or hypert ension. The overall risk of rebleeding is 50% w it hin
t he f irst 6 mont hs of present at ion and t hen 3% per year [233] . Delayed cerebral
ischemia associat ed w it h cerebral vasospasm is now t he leading cause of deat h
and disabilit y among pat ient s w it h aneurysmal SAH. Angiographic st udies
demonst rat e vasospasm in up t o 70% of pat ient s. Clinically signif icant cerebral
vasospasm occurs in one-t hird of pat ient s w it h aneurysmal SAH. Cerebral
vasospasm develops gradually, peaks around days 6 t hrough 10, and usually
subsides in 3 w eeks af t er aneurysmal SAH [20] . Cerebral vasospasm is
charact erized by increasing headaches, meningismus, low -grade f ever,
decreased alert ness, and f ocal neurologic def icit s t hat correspond t o t he region
of t he brain supplied by t he art eries in spasm, usually near t he t errit ory of
dist ribut ion of t he art ery aff ect ed by t he aneurysm. The most reliable predict or
f or t he development of cerebral vasospasm is t he amount and dist ribut ion of
blood on t he CT scan af t er SAH. A t hick, localized clot or diff use SAH is more
commonly seen in pat ient s w it h poor neurologic st at us [2] .
Repeat ed hemorrhages int o t he subarachnoid space can give rise t o superf i ci al
si derosi s of the CNS charact erized by sensorineural deaf ness and cerebellar
at axia. O t her f eat ures include dement ia, hydrocephalus, cort icospinal t ract
signs, anosmia, bladder dist urbance, anisocoria, ext raocular mot or palsies, opt ic
neuropat hy, nyst agmus, dysart hria, neck or backache, sensory signs, bilat eral
sciat ica, lumbosacral radiculopat hies, and ot her low er mot or neuron signs. O t her
vascular lesions associat ed w it h superf icial siderosis of t he CNS include
art eriovenous malf ormat ions, unrupt ured int racranial aneurysms, cavernous
malf ormat ions, and t elangiect asias. Superf icial siderosis can also be caused by
chronic bleeding f rom a brain or spinal cord t umor—most commonly a cauda
equina myxopapillary ependymoma, post erior f ossa t umors, hemispherect omy,
radiot herapy, cervical root avulsion w it h subsequent pseudomeningocele
f ormat ion, cervical or lumbar meningoceles, subdural hemat oma, and t rauma
associat ed w it h w arf arin use. O t her sources include meningiomas,
oligodendrogliomas, pineocyt omas, paragangliomas, repair of occipit al
encephalocele and neonat al int ravent ricular bleeding [102, 81] .
I n some pat ient s a source of t he subarachnoid bleeding is not f ound [6, 66, 231] .
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> Table of C ontents > C hapter 22 - The Loc aliz ation of Les ions C aus ing C om a
Chapter 22
The Localization of Lesions Causing Coma
Most causes of coma speedily t hreat en lif e or recovery of neurologic f unct ion.
Theref ore, t hey must be prompt ly ident if ied and t reat ed. Unf ort unat ely, pat ient s
w it h a depressed level of alert ness cannot give an account of t he event s leading
t o t heir sit uat ion, and of t en no one w ho has observed t he pat ient bef ore
admission is available t o provide such inf ormat ion. Theref ore, t he physician has
t o rely on examinat ion of t he pat ient , not only t o localize t he damaged anat omic
st ruct ures but also t o ident if y t he off ending agent . The examinat ion should be
t hought f ul and w ell inf ormed but not necessarily long. A delay in prot ect ing t he
airw ay of a poorly responsive pat ient may cause irreparable neurologic damage
[ 119, 177] .
The diagnosis of impaired alert ness and coma is w ell review ed in some excellent
monographs [114, 183] . The f ollow ing pages draw heavily f rom t hese sources.
The t opic of deat h based on neurologic crit eria (brai n death), covered by several
review s and regulat ed at many healt h care f acilit ies, f alls out side t he scope of
t his chapt er [8, 75, 173] .
Coma, Akinetic M utism, and Locked-In Syndrome

Terms such as coma, stupor, l ethargy, and t he like indicat e a depressed level of
alert ness. These t erms, how ever, f ail t o convey vit al inf ormat ion needed f or
neurologic localizat ion and management . Rat her t han using one of t hese t erms, a
descript ion of t he pat ient 's level of consciousness (incorporat ing some det ail of
t he pat ient 's responses t o diverse reproducible st imuli) f acilit at es communicat ion
among members of t he healt h care t eam, enhances consist ency in successive
evaluat ions of t he pat ient , and set s t he basis f or a rat ional diagnost ic
assessment . For inst ance, st at ing, “t he pat ient w as st uporous” provides lit t le
inf ormat ion. I nst ead, t he real sit uat ion can be conveyed much bet t er by
explaining in everyday English, “Mr. Z lay mot ionless in bed unless called loudly
by name, w hen he opened his eyes brief ly and looked t o t he lef t . He f ailed t o
answ er any quest ions or t o f ollow inst ruct ions. ”
Tw o t erms have gained accept ance among neurologist s and are w idely used:
akinet ic mut ism and locked-in syndrome. Aki neti c muti sm [ 136] ref ers t o a st at e
in w hich t he pat ient , alt hough seemingly aw ake, remains silent and mot ionless.
O nly t he eyes dart in t he direct ion of moving object s, such as t he examiner
approaching t he pat ient 's bed. The examiner, at t empt ing t o converse w it h a
pat ient in t his st at e, get s t he dist inct impression of f ailing t o draw t he pat ient 's
at t ent ion and int erest . Despit e t he lack of movement , t here are f ew signs
indicat ive of damage t o t he descending mot or pat hw ays. I nst ead, “f ront al
release signs, ” such as grasp or sucking, may be present . Pat ient s w ho remain
complet ely mot ionless are not seen as of t en as t hose w ho move one side or one
arm in a st ereot yped f ashion but in every ot her respect f it int o t he syndrome of
akinet ic mut ism. I n such cases, t he paralyzed side may display signs of
cort icospinal t ract involvement , such as hyperref lexia and a Babinski's sign.
I f a hist ory is available, akinet ic mut ism can be usually dist inguished f rom
psychogenic (of t en cat at onic) unresponsiveness. O t herw ise, t he diagnosis may
be diff icult . Part icularly w hen exposed t o painf ul st imuli (such as t hose caused
by soiled linen or a decubit us ulcer) or t o inf ect ion, pat ient s w it h akinet ic mut ism
appear excit ed and t achycardic and perspire heavily, t hereby superf icially
resembling a cat at onic pat ient . Signs of f ront al release or cort icospinal t ract
damage f avor
t he diagnosis of akinet ic mut ism. I n t he cat at onic pat ient , t he

elect roencephalogram (EEG ) is normal (of t en desynchronized, w it h low -volt age
f ast act ivit y), but in t he pat ient w it h akinet ic mut ism t he EEG of t en show s slow -
w ave abnormalit ies.
Lesions t hat cause akinet ic mut ism aff ect bilat erally t he f ront al region (ant erior
cingulat e gyri), t he diencephalo-mesencephalic ret icular f ormat ion, t he globus
pallidus, or t he hypot halamus [29, 90, 98] . Common causes are anoxia, head
t rauma, cerebral inf arct ion, severe acut e hydrocephalus, and direct compression
by t umors [93, 168] . O t her ext ensive lesions, such as air embolism or end-st age
degenerat ive or inf ect ious brain disorders, such as Creut zf eldt -Jakob disease,
can also cause t his syndrome [2, 48, 105, 145, 170] . Met abolic or ict al
disorders disrupt ing t he same areas may give rise t o a t ransient disorder of
alert ness similar t o akinet ic mut ism [6, 138] . A syndrome of t ransient mut ism and
relat ive akinesia may occur a f ew days af t er midline cerebellar or f ourt h
vent ricular surgery [16, 19, 34] . O ne such pat ient improved af t er dopaminergic
st imulat ion, suggest ing involvement of t he dopaminergic pat hw ays, at least in
some cases [16] . Hyperki neti c muti sm, w it h cont inuous bilat eral ballism and
dyst onia, has been described in a diabet ic w it h mult iple subcort ical and cort ical
inf arct s [50] .
When t he cerebral hemispheres have sust ained severe and w idespread damage
(such as t hat due t o severe t rauma, anoxia, or encephalit is), t he pat ient may,
af t er some w eeks of complet e unresponsiveness, evolve int o a sit uat ion similar
t o akinet ic mut ism, w it h t he ret urn of sleep–w ake cycles. These pat ient s,
how ever, demonst rat e obvious signs of pronounced bilat eral cort icospinal t ract
damage. This sit uat ion, in w hich t he pat ient 's f unct ions are rest rict ed t o t he
aut onomic sphere, has been t ermed t he vegetati ve state [ 3, 159, 160] . The
vegetati ve state has been def ined as a chronic neurologic condit ion charact erized
by lack of aw areness of self and ext ernal st imuli, accompanied by sleep–w ake
cycles, w it h preservat ion of vit al veget at ive f unct ions, such as cardiac f unct ion,
respirat ion, and maint enance of blood pressure. Pat ient s in a veget at ive st at e
show no evidence of sust ained, reproducible, purposef ul, or volunt ary behavioral
responses t o visual, audit ory, t act ile, or noxious st imuli; show no evidence of
language comprehension or expression; have bow el and bladder incont inence;
and have variably preserved cranial nerve and spinal ref lexes. G iven t hat mot or
responses on t he part of t he pat ient are needed t o evaluat e t he presence of
aw areness of self and ext ernal st imuli, in many of t hese pat ient s w it h severe
damage t o mot or mechanisms it is very diff icult t o assess t he degree of
aw areness. The presence of ext ensive damage on magnet ic resonance imaging
(MRI ) or comput ed t omography (CT) scan is helpf ul but does not def ine t his
issue eit her [176] . I n pat ient s in t he veget at ive st at e or in t he minimally
conscious st at e w it h ext ensive damage on neuroimaging, f unct ional brain imaging
has allow ed t he det ect ion of responses t o select ive st imuli, such as t he pat ient 's
name [76, 144] .
Persi stent vegetati ve state is def ined as a veget at ive st at e present 1 mont h af t er
acut e t raumat ic or nont raumat ic brain injury or last ing f or at least 1 mont h in
pat ient s w it h degenerat ive or met abolic disorders or development al
malf ormat ions [3, 159, 160] . Recovery of consciousness f rom a post t raumat ic
persist ent veget at ive st at e is unlikely af t er 12 mont hs in adult s and children [89] .
Recovery f rom a nont raumat ic persist ent veget at ive st at e af t er 3 mont hs is
exceedingly rare in bot h adult s and children [160] .
The l ocked-i n syndrome ref ers t o a condit ion in w hich t he pat ient is mut e and
mot ionless (de-eff erent ed) but remains aw ake, alert , aw are of self , and capable
of perceiving sensory st imuli. Alt hough horizont al eye movement s are of t en
impaired due t o t he involvement of t he paramedian pont ine ret icular f ormat ion
(PPRF), t he pat ient 's level of alert ness can be gleaned f rom his/ her response t o
commands involving vert ical eye movement s or eyelid movement s. The EEG
ref lect s t he pat ient 's st at e of w akef ulness. The locked-in syndrome is usually
due t o basilar art ery t hrombosis w it h vent ral pont ine inf arct ion, pont ine
hemorrhage or t umor, or cent ral pont ine myelinolysis (osmot ic demyelinat ion
syndrome) [47, 94] . These lesions involve t he descending mot or pat hw ays
bilat erally in t he basis pont is but spare t he more dorsal ret icular f ormat ion.
Bilat eral vent ral midbrain lesions [21, 38, 92] , t ent orial herniat ion [64, 179] ,
G uillain-Barré syndrome [7, 120] , or myast henia gravis may rarely cause t his
syndrome. I n locked-in syndrome due t o mesencephalic lesions, bilat eral pt osis
and vert ical (as w ell as horizont al) opht halmoplegia are present . Fou ri re
prodromi que (pat hologic laught er at t he onset of a st roke) may rarely herald t he
onset of a bilat eral vent ral pont ine st roke leading t o a locked-in syndrome [171] .
Anatomic Substrate of Alertness

I n general, t he maint enance of consciousness depends on int eract ion bet w een
t he ascending ret icular act ivat ing syst em (ARAS) and t he cerebral hemispheres.
Damage t o t he ARAS, described in
animals by Moruzzi and Magoun in 1949 [96] , induces a st at e of coma in w hich

t he animal becomes unresponsive and it s EEG show s sleep pat t erns despit e
vigorous sensory st imulat ion. I n humans, t he ARAS lies in t he paramedian
t egment al region of t he post erior port ion of t he pons and midbrain [106] . I t is a
complex polysynapt ic f iber syst em t hat ext ends f rom t he superior half of t he
pons t hrough t he midbrain t o t he post erior port ion of t he hypot halamus and t o
t he t halamic ret icular f ormat ion (Fig. 22-1). The t halamus is t he source of diff use
t halamocort ical project ions t hat regulat e and coordinat e cort ical act ivit y [54, 82] .
Sedat ive drugs act , at least in part , by int erf ering w it h t he synapt ic net w ork of
t he ARAS, w hich is played on by sensory st imuli.
FI G URE 22-1 Ascending ret icular act ivat ing syst em (ARAS). The dot t ed area
in t his midsagit t al sect ion of t he brain corresponds t o t he approximat e
locat ion of t he ARAS in t he upper brainst em and t he diencephalon.
The medial longit udinal f asciculi, w hich connect t he abducens and oculomot or
nuclei, and t he oculomot or and t rochlear nuclei t hemselves are sit uat ed amid t he
neurons of t he pont ine and midbrain port ions of t he ARAS. Theref ore, w hen
unresponsiveness is caused by brainst em damage, t he lesion aff ect s t he
mechanisms of ocular mot ilit y as w ell, and it s locat ion can of t en be det ermined
by abnormal pat t erns of ocular mot ilit y.
Bilat eral cerebral hemispheric lesions may cause t ransient coma, part icularly
w hen t hey involve t he mesial f ront al region. Large unilat eral lesions of t he
dominant hemisphere may occasionally cause t ransient unresponsiveness, even
in t he absence of a mass eff ect [1] .
I n t he diencephalon, post erior hypot halamic lesions induce prolonged
hypersomnia. Acut e bilat eral damage of t he paravent ricular t halamic nuclei is
at t ended by t ransient unresponsiveness, f ollow ed, w hen t he lesions are large, by
severe amnest ic dement ia (see Chapt er 18).
Signs w ith Localizing Value in Coma

I n a comat ose pat ient , t he respirat ory pat t ern, pupillary response, eye
movement s, and posit ion or movement s of t he limbs provide import ant clues t o
t he anat omic sit e and nat ure of t he injury.
Respiratory Patterns
Alt hough t he respirat ory pat t ern of a pat ient in coma may be helpf ul in localizing
t he level of st ruct ural dysf unct ion in t he neuraxis [150] , met abolic abnormalit ies
may aff ect t he respirat ory cent ers of t he pons (pneumot axic and apneust ic) and
medulla (expirat ory and inspirat ory) and result in pat t erns resembling t hose due
t o st ruct ural disease (Fig. 22-2). Theref ore, caut ion and a t horough evaluat ion of
t he met abolic st at us of t he pat ient must guide t he int erpret at ion of respirat ory
changes. I n pat ient s w ho
have lost all respirat ory ref lexes and are int ubat ed, t he self -cycling of t he
vent ilat or may erroneously suggest t hat t he pat ient is t riggering it [178] .
FI G URE 22-2 Respirat ory pat t erns charact erist ic of lesions at diff erent
levels of t he brain.
Posthyperventilation Apnea
This condit ion ref lect s mild bilat eral hemispheric dysf unct ion. Because
demonst rat ion of t his respirat ory abnormalit y requires t he pat ient 's act ive
cooperat ion, t his sign is ment ioned here mainly t o clarif y t he genesis of ot her
respirat ory pat t erns. To elicit t his phenomenon, t he pat ient is simply asked t o
t ake f ive deep breat hs. This maneuver normally decreases art erial pCO2 by
about 10 mm Hg and, in t he healt hy pat ient , is f ollow ed by a very brief period of
apnea (<10 seconds). The st imulus f or rhyt hmic breat hing w hen t he pCO2 is
low ered probably originat es in f orebrain st ruct ures, because sleep, obt undat ion,
or bilat eral hemispheric dysf unct ion abolish it . Theref ore, w hen bilat eral
hemispheric lesions are present , t he post hypervent ilat ion apnea last s f or as long
as 20 or 30 seconds.
Cheyne-Stokes Respiration
This t ype of respirat ion consist s of brief periods of hyperpnea alt ernat ing
regularly w it h even short er periods of apnea. Af t er t he apneic phase, t he
amplit ude of respirat ory movement s increases gradually t o a peak and t hen
slow ly w anes t o apnea. Not only does vent ilat ion f luct uat e periodically, but also
during t he hyperpneic st age t he pat ient becomes more alert , t he pupils may
dilat e t ow ard normal f rom t he miosis charact erist ic of diencephalic dysf unct ion,
and t he mot or behavior ref lect s cont rol by higher cent ers (e. g. , decort icat e
post uring yields t o semipurposef ul movement s). The eyelids may open during t he
rapid breat hing phase and close during t he slow breat hing phase.
Cheyne-St okes respirat ion represent s a more severe degree of
post hypervent ilat ion apnea in w hich t he respirat ory drive becomes more closely
dependent on t he pCO2 . Because t he “smoot hing eff ect ” provided by f orebrain
st ruct ures has been removed, pCO2 accumulat ion causes hyperpnea, w hich in
t urn induces a drop in pCO2 . Wit h t his drop t he respirat ory st imulus ceases, and
a period of apnea ensues.
This respirat ory pat t ern may f ollow bilat eral w idespread cort ical lesions but is
more likely t o be associat ed w it h bilat eral t halamic dysf unct ion and has also
been described w it h lesions of t he descending pat hw ays anyw here f rom t he
cerebral hemispheres t o t he level of t he upper pons [102] . Met abolic
dist urbances, such as uremia, diff use anoxia, and heart f ailure, of t en underlie
t his breat hing disorder. This pat t ern of respirat ion may also be seen in some
elderly individuals during sleep and in some normal individuals at high alt it udes.
Cheyne-St okes respirat ion in pat ient s w it h suprat ent orial mass lesions may
indicat e incipient t ranst ent orial herniat ion [114] .
Hyperventilation w ith Brainstem Injury

Pat ient s w it h lesions of t he midbrain and pons of t en have prolonged and rapid
hyperpnea. Because most of t hese pat ient s are relat ively hypoxic despit e t he
excessive vent ilat ory eff ort , t his t ype of breat hing cannot t ruly be called
neurogenic hypervent ilat ion. I n a f ew cases w here pulmonary or met abolic
causes of hypervent ilat ion w ere absent , brainst em t umors w ere f ound at
aut opsy. I n t hese cases, t umoral met abolism may have low ered t he pH of t he
local cerebrospinal f luid, t hereby providing a st imulus t o t he respirat ory cent er of
t he medulla [113] .
Cent ral neurogenic hypervent ilat ion, responsive t o morphine and met hadone,
occurred w it h an ast rocyt oma cent ered in t he medial t egment al parapont ine
ret icular f ormat ion [53] .
Apneustic Breathing
Apneust ic breat hing is charact erized by a long inspirat ory pause, af t er w hich t he
air is ret ained f or several seconds and t hen released. This abnormalit y appears
w it h lesions of t he lat eral t egment um of t he low er half of t he pons.
Cluster Breathing
Breat hing w it h a clust er of breat hs f ollow ing each ot her in an irregular sequence
may result f rom low pont ine or high medullary lesions.
Ataxic Breathing
This t ype of breat hing has a complet ely irregular pat t ern (also called t he at rial
f ibrillat ion of respirat ion) in w hich inspirat ory gasps of diverse amplit ude and
lengt h are int ermingled w it h periods of apnea. This respirat ory abnormalit y, of t en
present in agonal pat ient s, heralds complet e respirat ory f ailure and f ollow s
damage of t he dorsomedial medulla. The most common et iologies f or t his pat t ern
include cerebellar or pont ine hemorrhages, t rauma, and post erior f ossa t umors.
Less of t en, a paramedian medullary inf arct (usually due t o severe
at herosclerosis of a vert ebral art ery) may cause t his syndrome. The classic
breat hing pat t ern described by Biot w as at axic breat hing in pat ient s w it h severe
meningit is [114] .
“Ondine's Curse”
Pat hw ays f rom t he cerebral cort ex subserving volunt ary respirat ion are separat e
f rom t hose descending f rom t he medulla subserving aut omat ic respirat ion;
t heref ore, select ive impairment of aut omat ic or volunt ary breat hing is possible
[ 150] . Descending pat hw ays t hat are under volunt ary cont rol t ravel w it hin t he
dorsal cord in t he region of t he cort icospinal t ract , w hereas pat hw ays f rom
primary medullary respirat ory cent ers t ravel in t he vent rolat eral cord, w it h
anat omic separat ion of inspirat ory and expirat ory pat hw ays [150] .
O ndine's curse ref ers t o t he loss of aut omat ic breat hing during sleep. This
respirat ory pat t ern, obviously absent in comat ose pat ient s, is ment ioned here
because it occurs w it h low er brainst em dysf unct ion. Lesions responsible f or t his
condit ion have a similar or somew hat low er locat ion t han t hose t hat cause at axic
breat hing but are smaller or develop more slow ly. Bot h unilat eral [4, 80] and
bilat eral [28] medullary t egment al inf arct s have produced t his syndrome. This
disorder has also been recorded w it h high cervical cord lesions af t er surgical
sect ion of t he vent rolat eral spinal cord f or pain relief [70, 166] , probably
because of ret iculospinal t ract int errupt ion. O f 12 pat ient s w ho died w it h
presumed O ndine's curse af t er high cervical percut aneous cordot omy f or pain,
all had lesions involving t he region of t he ant erolat eral f uniculus in t he C2
segment cont aining pain f ibers act ivat ed f rom t he second t o f if t h t horacic
dermat omes [70] .
Cent ral hypovent ilat ion may be caused by unilat eral caudal brainst em inf arct ion
[ 10] . O ne pat ient w it h nearly complet e loss of vent ilat ion involving bot h t he
aut omat ic and volunt ary component s had an inf arct involving t he ret icular
f ormat ion, nucleus t ract us solit arius, nucleus ambiguus, and nucleus
ret roambiguus on t he right , w hich spared t he dorsal mot or nucleus of t he vagus
nerve and sensory and cort icospinal t ract s. A second pat ient w it h hypovent ilat ion
more select ively involving aut omat ic responses (O ndine's curse) had an inf arct
involving t he medullary ret icular f ormat ion and nucleus ambiguus t hat spared t he
nucleus t ract us solit arius. These cases suggest t hat unilat eral involvement of t he
pont omedullary ret icular f ormat ion and nucleus ambiguus is suff icient f or
generat ing loss of aut omat ic respirat ion, w hereas an associat ed lesion of t he
nucleus t ract us solit arius may lead t o more severe respirat ory f ailure involving
aut omat ic and volunt ary responses [10] . Cent ral hypovent ilat ion or apnea has
also been report ed w it h bilat eral damage t o t he high cervical spinal cord or w it h
dorsolat eral lesions of t he t egment um of t he medulla. A select ive paresis of
volunt ary but not aut omat ic respirat ion has been described w it h a discret e
inf arct ion of t he vent ral basis pont is, f urt her suggest ing t hat aut omat ic and
volunt ary respirat ion are cont rolled by anat omically independent pat hw ays [97] .
Temperature Changes
Hypert hermia is not uncommon in coma caused by severe t raumat ic brain injury
[ 161] . Pat ient s in coma are predisposed t o inf ect ion, but in a proport ion of
pat ient s, hypert hermia may be neurogenic, t hat is, relat ed t o an alt ered
t emperat ure regulat ion syst em. Many of t hese inst ances are caused by
hypot halamic dysf unct ion (see Chapt er 17). Neurogenic hypert hermia has also
been described w it h pont ine t egment al lesions [106] .
The Pupils
Pupillary shape, size, symmet ry, and response t o light provide valuable clues t o
brainst em and t hird cranial nerve f unct ion. The pupillary light ref lex
is resist ant t o met abolic dysf unct ion. Abnormalit ies of t his ref lex, part icularly
w hen unilat eral, indicat e st ruct ural lesions of t he midbrain or oculomot or nerve. A
f ew except ions are not ew ort hy. At ropinic agent s, inst illed int o t he eyes, applied
on t he skin (e. g. , t ransdermal scopolamine) [22] , ingest ed, or given during
cardiopulmonary resuscit at ion, may cause pharmacologic iridoplegia. I n t hese
cases, a solut ion of 1% pilocarpine applied t o t he eye w ill f ail t o const rict t he
pupils, w hereas in t he case of anoxic pupillary dilat ion, t his cholinergic agent ,
act ing direct ly on t he const rict or of t he iris, produces miosis. Because many
pat ient s in coma have small pupils, ant icholinergic agent s are somet imes used t o
f acilit at e visualizat ion of t he opt ic f undi, t hereby eliminat ing a pot ent ially usef ul
diagnost ic indicat or. I n many cases, a bet t er w ay t o obt ain pupillary dilat ion is
by pinching t he skin of t he neck (ci l i ospi nal ref l ex). G lut et himide (Doriden)
induces unequal pupils t hat are midsized or slight ly dilat ed and poorly responsive
t o light . O t her agent s t hat may cause unreact ive pupils include barbit urat es (t he
pupillary light ref lex is more of t en ret ained), succinylcholine, and, rarely, ot her
ant iconvulsant s, lidocaine, phenot hiazines, met hanol, and aminoglycoside
ant ibiot ics [23, 39] . Agent s ot her t han glut et himide or ant icholinergic drugs cause
pupillary dilat ion only w hen t aken in massive amount s, enough t o eliminat e
respirat ory ref lexes or, in t he cases of succinylcholine and aminoglycoside
ant ibiot ics, generalized neuromuscular junct ion blockade. Usually, t he amount of
sedat ive drug is insuff icient t o abolish t he pupillary light ref lex. Hypot hermia and
acut e anoxia may also cause unreact ive pupils, w hich, if persist ent beyond
several minut es af t er an anoxic insult , carry a poor prognosis [35] .
FI G URE 22-3 Pupillary responses charact erist ic of lesions at diff erent levels
of t he brain.
The areas of t he brain and anat omic pat hw ays t hat mediat e t he pupillary light
ref lex are review ed in Chapt er 8, in w hich t he origin and course of sympat het ic
and parasympat het ic inf luences on t he iris muscle are described.
Various st ruct ural lesions causing coma may be associat ed w it h pupillary
abnormalit ies (Fig. 22-3):
1. Sl eep or bi l ateral di encephal i c dysf uncti on (met abolic coma) is accompanied

by small pupils t hat react w ell t o light (“diencephalic” pupils).
2. Unilat eral hypothal ami c damage induces miosis and anhidrosis on t he side of
t he body ipsilat eral t o t he lesion.
3. Mi dbrai n lesions causing coma usually produce dist inct pupillary
abnormalit ies. Tectal or pretectal lesions aff ect ing t he post erior commissure
abolish t he light ref lex, but t he pupils, w hich are midsized or slight ly large,
may show spont aneous oscillat ions in size (hippus) and become larger w hen
t he neck is pinched (ciliospinal ref lex). Tegmental lesions, w hich involve t he
t hird nerve nucleus, may cause irregular const rict ion of t he sphinct er of t he
iris, w it h a result ant pear-shaped pupil or displacement of t he pupil t o one
side (midbrain corect opia) [146] . The pupils, of t en unequal, t end t o be
midsized and lack light or ciliospinal responses. Unilat eral or bilat eral oval
pupi l s (w hich may be f ixed t o light ) may occur w it h severe cerebrovascular
lesions t hat injure t he oculomot or or pupillomot or f ibers. The oval shape is
due t o nonunif orm paresis or paralysis of t he pupil sphinct er, w it h result ant
eccent ric ant agonist ic eff ect s of pupil dilat ors.
4. Ponti ne tegmental lesions cause small pupils due t o int errupt ion of t he
descending sympat het ic pat hw ays. Pinpoint pupils, w hich may be seen t o
const rict t o light w hen observed w it h a magnif ying glass, may occur w it h
pont ine hemorrhage, and are due t o a combinat ion of sympat het ic damage
and parasympat het ic irrit at ion.
5. Lateral ponti ne, l ateral medul l ary, and ventrol ateral cervi cal cord lesions
produce an ipsilat eral Horner syndrome.
6. O cul omotor nerve compression and elongat ion by herniat ion of t he uncus of
t he t emporal lobe (t hrough t he t ent orial incisura) aff ect pupillary f unct ion
earlier and more not iceably t han t he ext rinsic eye movement s subserved by
t his cranial nerve. Possible explanat ions f or pupillary dilat ion on t he side of a
mass lesion include compression of t he t hird cranial nerve by uncal herniat ion
beneat h t he t ent orial edge; compression of t he nerve by t he post erior
cerebral art ery or by t he hippocampal gyrus; st ret ching or buckling of t he
nerve by t ract ion at t he superior orbit al f issure, post erior clinoid, or clivus;
or compression of t he midbrain oculomot or complex [132] . The light ref lex is
sluggish or absent , and, unlike t he sit uat ion w it h midbrain involvement , t he
pupil becomes w idely dilat ed ow ing t o sparing of t he sympat het ic pat hw ays
(Hut chinson's pupil).
Ropper st udied t he pupil opposi te t he one already enlarged f rom
t ranst ent orial herniat ion in 13 pat ient s [130] . I n most pat ient s, t he pupil w as
init ially 2. 5 t o 4 mm in diamet er w it h a diminished or absent light react ion;
t his init ial phase w as f ollow ed by a slight reduct ion in pupil size, t hen
reenlargement t o great er t han t he original pupil size, all w it h preserved
roundness. Subsequent det eriorat ion varied, but a t ransit ional oval pupil
shape w as inf requent , and oculomot or f unct ion w as ot herw ise preserved unt il
bot h pupils w ere enlarged and f ixed t o light . Theref ore, subsequent
neurologic det eriorat ion in a pat ient w it h t ranst ent orial herniat ion can of t en
be appreciat ed by change in t he react ivit y and size of t he opposit e pupil
[ 130] . O t her report s have demonst rat ed a paradoxical init ial enlargement of
t he pupil opposit e t he side of a mass lesion, especially w it h acut e subdural
hemat oma [111] or int raparenchymal [20] or subarachnoid [86] hemorrhage.
7. O t her ocul omotor nerve lesions causing pupillary abnormalit ies are less
likely t o impair consciousness, except w hen associat ed w it h a subarachnoid
hemorrhage. Post erior communicat ing art ery aneurysms can compress t he
t hird nerve and a massive subarachnoid hemorrhage may result in coma.
Rarely, pat ient s w it h G uillain Barré syndrome may become complet ely
paralyzed and lose even t heir pupillary response [7, 120] . This complet e
locked-in st at e may be mist aken f or severe anoxic brain damage in t hese
pat ient s w ho are obviously prone t o anoxic event s [77] . How ever, in a
locked-in pat ient , t he EEG w ill show normal or slight ly slow brain act ivit y.
Wit h acut e neurosurgical lesions, f ixed pupils are not necessarily a sign of
irreversible coma. I n a series of 40 pat ient s w it h f ixed pupils, 25% of t hem made
a f unct ional recovery [141] . None of t hese pat ient s recovered af t er more t han 6
hours w it h f ixed pupils.
Eye Movements
The anat omic pat hw ays subserving eye movement s w ere review ed in Chapt er 8.
I n t he comat ose pat ient t he assessment of eye movement s helps t o det ermine
t he level of st ruct ural brainst em damage (Fig. 22-4) or t he dept h of coma
induced by met abolic agent s.
I n t he absence of volunt ary eye movement s, t he assessment of ocular mot ilit y in
comat ose pat ient s
relies heavily on ref lex eye movement s, including t he ocul ocephal i c ref l ex,
elicit ed by t he doll's eye maneuver, and t he ocul ovesti bul ar ref l ex, elicit ed by
inst illat ion of cold or w arm w at er int o t he ext ernal audit ory canal [14, 114] .
Caloric t est ing w it h 50 mL of ice w at er inst illed over 30 seconds int o t he ext ernal
audit ory canal, af t er t he head is raised 30 degrees and an int act t ympanic
membrane is document ed, provides a st ronger st imulus t han t he oculocephalic
ref lex. I f only t he lat t er ref lex is present , eit her caloric st imulat ion has been
perf ormed inadequat ely (e. g. , hindered by t he presence of w ax in t he ext ernal
audit ory canal) or t here is damage t o t he labyrint h (e. g. , by ot ot oxic ant ibodies)
or t he vest ibular nuclei in t he lat erosuperior medulla.
FI G URE 22-4 Eye movement abnormalit ies charact erist ic of lesions at

diff erent levels of t he brain. The responses t o cold caloric st imulat ion of t he
lef t ear are indicat ed in t he right -hand column. The f irst t w o responses at t he
t op show normal ext rinsic ocular mot ilit y w it h cold caloric st imulat ion of t he
lef t ear.
Because of t he absence of cort ical cont rol of eye movement s, t he comat ose
pat ient lacks volunt ary saccades, including t he quick phase of nyst agmus and
t racking eye movement s. I nst ead, if t he brainst em is int act , t he eyelids are
closed, and t he eyes, slight ly divergent , drif t slow ly f rom side t o side (rovi ng
eye movements). Spont aneous blinking requires an int act pont ine ret icular
f ormat ion. Blinking induced by a bright light is probably mediat ed by t he superior
colliculus and remains int act despit e occipit al damage. The absence of blinking
only on one side indicat es unilat eral nuclear, f ascicular, or peripheral f acial nerve
dysf unct ion. The eyelids may remain t onically ret ract ed because of f ailure of
levat or inhibit ion in some cases of pont ine inf arct ion (eyes-open coma) [ 57] .
The roving eye movement s of light coma cannot be volunt arily execut ed and are
t heref ore incompat ible w it h t he diagnosis of f eigned
unresponsiveness. As coma deepens, roving eye movement s disappear f irst ,

f ollow ed by t he oculocephalic ref lex; f inally, even cold w at er inst illed in t he ear
f ails t o induce eye movement s. I n met abolic coma, t he pupils may st ill react
w hen eye movement s cannot be elicit ed.
TABLE 22-1 Spontaneous Eye M ovements in

Comatose Patients
Movem ent Description Localization
Bilateral
Periodic Cyclic cerebral
alternating gaze horizontal damage, rarely
(ping-pong gaze) rowing posterior fossa
lesion
Slow deviation
Repetitive out, rapid Metabolic
divergence return to encephalopathy
primary
Vertical,
Nystagmoid
horizontal, or Middle or low
jerking of a single
rotary pontine
eye
movements
Small-
amplitude
vertical Diffuse
Status epilepticus
(occasionally encephalopathy
horizontal) eye (e.g., anoxia)
movements
Pontine, extra-
axial posterior
Fast down,
Ocular bobbing fossa mass,
slow up
diffuse
encephalopathy
Anoxia,
Inverse ocular poststatus
Slow down,
bobbing (ocular epilepticus
fast up
dipping) (diffuse
encephalopathy)
Diffuse
Reverse ocular Fast up, slow
encephalopathy,
bobbing down
rarely pontine
Slow-upward
ocular bobbing Diffuse
Slow up, fast
(converse ocular encephalopathy,
down
bobbing, reverse rarely pontine
ocular dipping)
Pretectal “V pattern”: Pretectal (e.g.,

pseudobobbing down and in hydrocephalus)
Pendular,
Vertical ocular vertical
isolated eye Pontine
myoclonus
movements
O t her spont aneous eye movement s seen in comat ose pat ient s include t he
f ollow ing (Table 22-1):
1. Short-cycl e peri odi c al ternati ng gaze (pi ng-pong gaze), w hich involves
roving of t he eyes f rom one ext reme of horizont al gaze t o t he ot her and
back, w it h each oscillat ing cycle t aking 2. 5 t o 8 seconds [30, 51, 88, 155] .
This f inding usually indicat es bilat eral cerebral damage (e. g. , bilat eral
cerebral inf arct s) w it h an int act brainst em, but it has also been described
w it h post erior f ossa hemorrhage, basal ganglia inf arct s, hydrocephalus, and
overdose of t he monoamine oxidase inhibit or t ranylcypromine [51, 72, 73,
124, 148, 172] . The disorder may occasionally occur in coma w it h no
st ruct ural hemispheric lesion [71, 184] . A man in his t w ent ies, w it h chronic
hydrocephalus f rom inf ancy and absent vert ical eye movement s, had ping-
pong gaze since childhood only w hen aw ake [73] . O ne case w as at t ribut ed t o
bilat eral lesions of t he cerebral peduncles [71] .
Crevit s and Decruyenaere described t hree pat ient s w it h ping-pong gaze (due
t o hepat ic encephalopat hy, carbon monoxide int oxicat ion, and hypoxia,
respect ively) and proposed t hat t his t erm be reserved f or t hose f orms of
periodic alt ernat ing gaze w it hout a silent period [24] . They not ed t hat t he
only const ant clinical implicat ion of ping-pong gaze w as int egrit y, at least in
part , of t he low er brainst em, w it h lack of cort ical inhibit ion of t he horizont al
gaze cent ers in t he brainst em. This disorder of ocular mot ilit y had no
prognost ic value [24] .
Ping-gong gaze must be diff erent iat ed f rom peri odi c al ternati ng gaze
devi ati on, w hich is an alt ernat ing horizont al conjugat e gaze deviat ion last ing
1 t o 2 minut es in each direct ion. Periodic alt ernat ing gaze deviat ion usually
occurs in alert pat ient s w it h st ruct ural lesions involving t he cerebellum and
brainst em, such as t he Arnold-Chiari malf ormat ion
or medulloblast oma, but it has been described in obt unded or comat ose
pat ient s w it h hepat ic encephalopat hy [5] .
2. Repeti ti ve di vergence is rarely seen in pat ient s w it h coma f rom met abolic
encephalopat hy (e. g. , hepat ic encephalopat hy) [100] . Wit h t his disorder, t he
eyes are in midposit ion or slight ly divergent at rest . They t hen slow ly deviat e
out , become f ully deviat ed f or a brief period, and t hen rapidly ret urn t o t he
primary posit ion bef ore repeat ing t he cycle. These mot ions are synchronous
in bot h eyes.
3. Nystagmoi d jerki ng of a si ngl e eye, in a vert ical, horizont al, or rot at ory
f ashion, may occur w it h mid- t o low er pont ine damage [114] . Pont ine lesions
occasionally give rise t o disconjugat e rot at ory and vert ical movement s of t he
eyes, in w hich one eye may rise and int ort as t he ot her f alls and ext ort s
[ 114] . This t ype of movement should not be conf used w it h see-saw
nyst agmus, w hich is very seldom seen in comat ose pat ient s [58] .
4. El ectrographi c status epi l epti cus w it hout appendicular mot or manif est at ions,
due t o anoxia, may result in brisk, small-amplit ude, mainly vert ical
(occasionally horizont al) eye movement s det ect able by passive lid elevat ion
[ 151] .
5. O cul ar bobbi ng ref ers t o int ermit t ent , of t en conjugat e, brisk, bilat eral
dow nw ard movement of t he eyes w it h slow ret urn t o midposit ion [36] . Bot h
mesencephalic and medullary burst neuron cent ers may play a part in it s
genesis [133] . Cold calorics may increase t he amplit ude and f requency of
t he bobbing or have no eff ect [25] . O cular bobbing has been associat ed w it h
int rinsic pont ine lesions (e. g. , hemorrhage, t umor, inf arct ion, cent ral pont ine
myelinolysis) [56, 74, 91, 133, 163, 184] , ext ra-axial post erior f ossa masses
(e. g. , aneurysm rupt ure or cerebellar hemorrhage or inf arct ion) [11, 45,
104] , diff use encephalit is [139] , Creut zf eldt -Jakob disease [133] , and t oxic-
met abolic encephalopat hies (e. g. , acut e organophosphat e poisoning) [32, 46,
156] . “Typical” ocular bobbing, w hich is associat ed w it h preserved horizont al
eye movement s, is t hought t o be specif ic but not pat hognomonic of acut e
pont ine injury, w hereas “at ypical” ocular bobbing, w hich is associat ed w it h
absent horizont al eye movement s, is t hought t o be less helpf ul in predict ing
t he sit e of abnormalit y [156] . Monocular bobbing (pareti c bobbi ng), w hich
consist s of a quick dow nw ard movement of one eye and int orsion or no
movement in t he ot her eye, may occur if t here is a coexist ent unilat eral
f ascicular oculomot or nerve palsy [156] . Disconjugat e ocular bobbing, w it h
movement s involving somet imes one eye and somet imes t he ot her, may also
occur w it hout oculomot or nerve palsy [40] .
6. Inverse ocul ar bobbi ng (ocul ar di ppi ng or f ast -upw ard ocular bobbing) [41,
66, 83, 91, 128, 140, 153, 169] consist s of a slow -dow nw ard eye movement
w it h f ast ret urn t o midposit ion, w hich may occur in anoxic coma or af t er
prolonged st at us epilept icus [66, 126, 153] . I t probably ref lect s diff use brain
dysf unct ion rat her t han a single st ruct ural lesion because brainst em
horizont al gaze ref lexes are usually int act . O cular dipping has also been
described associat ed w it h deaf ness in a pat ient w it h pinealoblast oma [165] .
Inverse/ reverse ocul ar bobbi ng consist s of inverse ocular bobbing in w hich
t he eyes do not st op on rapidly ret urning t o primary posit ion but shoot int o
upgaze and slow ly ret urn t o midposit ion [135, 164] .
7. Reverse ocul ar bobbi ng (f ast -upw ard ocular bobbing) consist s of f ast -
upw ard eye movement w it h a slow ret urn t o midposit ion, w hich may occur in
pat ient s w it h met abolic encephalopat hy, viral encephalit is, or pont ine
hemorrhage [13, 41, 91] . I t has been described w it h coma, due t o combined
phenot hiazine and benzodiazepine poisoning [79] . O ccasionally, ocular
bobbing, ocular dipping, and reverse bobbing may occur at diff erent t imes in
t he same pat ient [135] .
8. Sl ow-upward ocul ar bobbi ng (converse ocul ar bobbi ng or reverse ocul ar
di ppi ng) is charact erized by slow -upw ard eye movement s f ollow ed by f ast
ret urn t o midposit ion [41, 91] . This eye movement disorder has been
described w it h pont ine inf arct ion (t he pat ient had a one-and-a-half syndrome)
[ 41] and w it h met abolic or viral encephalopat hy (i. e. , diff use cerebral
dysf unct ion) [91] .
9. Pretectal pseudobobbi ng has been described w it h acut e hydrocephalus [61]
and consist s of arrhyt hmic, repet it ive dow nw ard and inw ard (“V pat t ern”) eye
movement s at a rat e ranging f rom 1 per 3 seconds t o 2 per second and an
amplit ude of 1/ 5 t o 1/ 2 of t he f ull volunt ary range. These movement s may be
mist aken f or ocular bobbing, but t heir V pat t ern, t heir f ast er rat e, and t heir
pret ect al rat her t han pont ine-associat ed signs dist inguished t hem f rom t rue
pont ine bobbing. Theref ore, pat ient s w it h pret ect al pseudobobbing may have
abnormal pupillary light react ions, int act horizont al eye movement s, open
and of t en ret ract ed eyelids, a blink f requent ly preceding each eye

movement , and a mut e or st uporous rat her t han a comat ose st at e. Pret ect al
pseudobobbing probably represent s a variet y of convergence nyst agmus,
and it s presence usually indicat es t he need f or prompt surgical at t ent ion
(e. g. , hydrocephalus decompression) [61] . I t is possible t hat some cases of
“ocular bobbing” associat ed w it h t halamic hemorrhage or t ent orial herniat ion
may act ually be cases of pret ect al pseudobobbing.
10. Verti cal ocul ar myocl onus consist s of pendular, vert ical isolat ed movement s
of t he eyes not ed in pat ient s eit her locked-in or comat ose af t er severe
pont ine st rokes [62] . Their f requency is 2 Hz, and ot her rhyt hmic body
movement s at a similar f requency occur af t er a 6-w eek t o 9-mont h delay.
These movement s are generally associat ed w it h palat al myoclonus (palat al
t remor), w it h w hich t hey share a common mechanism [62] .
Abnormalities of Lateral Gaze

Conjugate Gaze
When bot h eyes remain deviat ed t ow ard t he same side in a comat ose pat ient ,
t he lesion may be in t he cerebral hemisphere (most of t en involving t he f ront al
eye f ields) or in t he pont ine t egment um. I n t he case of a hemi spheri c lesion,
unless t he pat ient is having a seizure, t he eyes “look t ow ard t he lesion” (aw ay
f rom t he hemiparet ic side) but can be brought t o t he ot her side w it h t he
oculocephalic maneuver, caloric t est ing, or bot h. A seizure originat ing in t he
f ront al or occipit al lobes may cause deviat ion of t he eyes and head aw ay f rom
t he lesion, but such deviat ion is brief and usually accompanied by nyst agmoid
jerks; as soon as t he seizure ceases, t he eyes ret urn t o “look” t ow ard t he lesion.
Thalamic and, rarely, basal ganglionic lesions, almost alw ays hemorrhagic, may
produce f orced deviat ion of t he eyes t o t he side cont ralat eral t o t he lesion
(wrong-way eyes) [ 162] . Very rarely, f ront al-perisylvian lesions may cause
w rong-w ay eyes [109] .
Predominant ly unilat eral lesions aff ect ing t he t egment um of t he l ower pons cause
a horizont al gaze palsy t ow ard t he side of t he lesion so t hat t he eyes look
t ow ard t he hemiparet ic side. Neit her t he oculocephalic maneuver nor caloric
t est ing overcomes a pont ine gaze palsy.
Coma due t o t oxic subst ances is of t en accompanied by impaired conjugat e eye
movement s, horizont al as w ell as vert ical [115] . Thiamine def iciency, causing
Wernicke's encephalopat hy, is a t reat able cause of opht halmoparesis and coma.
I t need not accompany alcoholism [185] .
Disconjugate Gaze
I solat ed f ailure of ocular adduct ion, in t he absence of pupillary changes and w it h
normal vert ical eye movement s (elicit ed by oculocephalic or oculovest ibular
ref lexes), indicat es a lesion of t he medial longit udinal f asciculus (MLF) in t he
upper pons ipsilat eral t o t he eye t hat f ails t o adduct . MLF involvement is
commonly bilat eral in comat ose pat ient s. Rarely, met abolic coma (such as t hat
due t o barbit urat es, amit ript yline [49] , or hepat ic f ailure [17] ) may induce a
t ransient MLF syndrome t hat can usually be overcome by vigorous caloric
t est ing.
Lat ent st rabismus may become apparent w hen t he level of alert ness is mildly
impaired but disappears in deep coma. Because st rabismus involves a single
muscle, it seldom mimics neurogenic oculoparesis except , perhaps, w hen
abduct ion is reduced.
Abnormalities of Vertical Gaze

I n pat ient s w it h light coma, upw ard gaze can be t est ed by holding t he eyelids
open and gent ly t ouching t he cornea w it h a w isp of cot t on or a similar object .
Wit h t his st imulus t he eyeballs t end t o roll upw ard (Bel l 's phenomenon). Unless
t he pat ient is int ubat ed or has a neck injury, t he doll's head maneuver can be
used t o elicit t he vert ical component of t he oculocephalic ref lex. I rrigat ion of
bot h ears w it h cold w at er induces dow nw ard deviat ion of t he eyes; w arm w at er
induces upw ard deviat ion.
Disconjugat e vert ical gaze in t he rest ing posit ion (skew devi ati on) may be seen
w it h lesions at diff erent areas of t he brainst em, w it h increased int racranial
pressure, or w it h hepat ic coma (see Chapt er 8). Persist ent deviat ion of t he eyes
below t he horizont al meridian signif ies brainst em dysf unct ion, w hich is of t en due
t o a st ruct ural lesion t hat aff ect s t he t ect um of t he midbrain but is occasionally
caused by met abolic encephalopat hy (e. g. , hepat ic coma [65] ). Tonic dow nw ard
deviat ion of t he eyes, of t en accompanied by convergence, may occur w it h
t halamic hemorrhage, probably due t o pressure on t he dorsal mesencephalon.
Forced dow nw ard deviat ion of t he eyes has also been report ed in pat ient s
f eigning coma [134] . Forced dow nw ard deviat ion of t he eyes during caloric
t est ing of t en occurs in coma induced by sedat ive drugs [149] . Sust ained upgaze
has been report ed w it h severe anoxic encephalopat hy [60] and w it h
phenot hiazine int oxicat ion. Paresis of upw ard gaze is usually present w it h
bilat eral midbrain t ect al damage. Dow nw ard gaze is pref erent ially aff ect ed by
bilat eral lesions of t he superomedial perirubral region in t he vent ral port ion of
t he origin of
t he Sylvian aqueduct f rom t he t hird vent ricle. I n many of t hese pat ient s t he lesion
ext ends int o t he medial t halamic nuclei [108] . Large midbrain t egment al lesions
abolish vert ical gaze. At rest , t he eyes remain in midposit ion or may be
disconjugat ely deviat ed in t he vert ical plane. Bi l ateral ptosi s new ly developed in
pat ient s w it h evolving massive hemispheric inf arct ion seems t o suggest
compression of t he midbrain [9] .
Corneal Reflex
The corneal ref l ex has a higher t hreshold in comat ose pat ient s. Nonet heless, it
must be elicit ed by a gent le and asept ic st imulus t o avoid t he risk of an inf ect ed
corneal ulcerat ion in pat ient s w it h decreased corneal sensit ivit y (as w it h cranial
nerve V lesions, ipsilat eral lat eral pont omedullary lesions, or cont ralat eral
pariet al lesions) [103] , or impaired eye closure (as w it h cranial nerve VI I lesions
and low pont ine lesions). I n t he lat t er case, t he st imulus may induce deviat ion of
t he jaw t o t he opposit e side (corneopterygoi d ref l ex), and, given an int act upper
pons and midbrain, t he eyes may roll upw ard (Bel l 's phenomenon).
Motor Activity of the Body and Limbs

When examining a pat ient in coma, observat ion of t he movement s and of t he t one
and ref lexes of t he limbs supplies inf ormat ion t hat has a less clear-cut localizing
value t han similar f indings in alert pat ient s. Rarely is a met abolic coma (not ably
hypoglycemic) accompanied by hemiparesis; how ever, ot her mot or pat t erns,
w idely know n as decorti cate (f lexor post uring) and decerebrate (ext ensor
post uring) rigidit y, are of t en produced by met abolic disorders [43] and do not
have t he st ruct ural implicat ions t hat t heir names, coined during experiment al
w ork, w ould suggest . O f course, st ruct ural damage t o t he origin or course of t he
mot or pat hw ays may give rise t o such pat t erns, w hich, in t hese cases, are of t en
asymmet ric. How ever, because met abolic coma is more f requent t han st ruct ural
coma, met abolic coma is of t en responsible f or t he mot or pat t erns discussed in
t he subsequent t ext (Fig. 22-5).
FI G URE 22-5 Decort icat e and decerebrat e post uring of t he limbs in
comat ose pat ient s.
I n l i ght coma, t he general mot or responses may oscillat e bet w een lying quiet ly in
bed and w ildly t hrashing about . The lat t er sit uat ion occurs w hen a painf ul
st imulus (such as t hat caused by a subarachnoid hemorrhage or a f ull bladder)
rouses t he pat ient , w hose diminished at t ent ion prevent s any coherent sequence
of movement s. Such pat ient s, how ever, t ry t o avoid painf ul st imuli by
appropriat ely w it hdraw ing a limb or using it t o brush off t he off ending agent .
G ent ly sliding a cot t on-t ipped st ick along t he pat ient 's f orehead of t en proves
enough of a st imulus t o obt ain such a response. Asymmet ric responses bet ray a
def icit of t he mot or or sensory pat hw ays, or bot h.
The t one of t he ext remit ies can be checked by lif t ing t he arms f rom t he bed and
f lexing t he pat ient 's knees and releasing t hem. I n light coma, t he limbs f all slow ly
t o t he rest ing posit ion. A paret ic limb f alls like a “dead w eight . ” Theref ore, a
hemiparesis, or even monoparesis, can be easily det ect ed.
Anoxic lesions of t he cerebral border zones may result in predominant damage t o
t he cort ex in t he area of represent at ion of t he arms. Such pat ient s may have
bilat eral arm w eakness w it h relat ively spared low er ext remit y f unct ion (man-i n-
the-barrel syndrome) [ 33] .
When t he level of coma deepens or a st ruct ural lesion aff ect s a cerebral
hemisphere and t he diencephalon, decorti cate ri gi di ty may appear; t his rigidit y is
cont ralat eral t o t he hemispheric lesion. Decort icat e rigidit y is charact erized by
adduct ion of t he shoulder and arm, f l exi on at the el bow, and pronat ion and
f lexion at t he w rist ; t he leg remains ext ended at t he hip and knee (Fig. 22-5).
Severe met abolic (e. g. , anoxic) disorders or lesions of t he upper brainst em give
rise t o decerebrate ri gi di ty, w hich is charact erized by extensi on and pronati on of
t he upper ext remit ies and f orcible plant ar f lexion of t he f oot (Fig. 22-5). Brought
about by painf ul st imuli, opi sthotonos develops periodically w it h hyperext ension
of t he t runk and hyperpronat ion of t he arms. I n experiment al animals,
decerebrat e rigidit y result s f rom brainst em t ransect ion at t he collicular level,
below t he red nuclei but leaving int act t he pont ine ret icular f ormat ion and
vest ibular nuclei. The act ion of t he vest ibular nuclei, unchecked by higher
cent ers, may explain t he increased ext ensor t one charact erist ic of decerebrat e
rigidit y. St ruct ural lesions t hat cause t his mot or pat t ern usually aff ect t he
midbrain and upper pons eit her direct ly, as in t he case of brainst em inf arct s, or
indirect ly, by ischemia produced by pressure arising in t he suprat ent orial
compart ment (dow nw ard herniat ion) or in t he post erior f ossa.
I n a given pat ient , one side may demonst rat e decort icat e post uring, w hereas t he
ot her side, innervat ed by t he mot or pat hw ays t hat have undergone great er
damage, displays decerebrat e rigidit y.
Abnormal extensi on of the arms wi th weak f l exi on of the l egs usually indicat es
damage of t he ponti ne tegmentum [ 114] . Wit h even low er lesions involving t he
medul l a, t ot al f laccidit y ensues.
Flaccidit y in a crit ically ill pat ient can also be produced by a polyneuropat hy
(“cri ti cal i l l ness neuropathy”). More recent ly, it has been recognized t hat many
cases of f laccidit y in comat ose pat ient s, part icularly t hose on st eroid t reat ment ,
are caused by a severe necrosis of t he t hick f ibers of st riat ed muscle cells
(“cri ti cal i l l ness myopathy”) [ 78, 84, 143] .
Clinical Presentations of Coma-Inducing Lesions

Depending on their Location
Metabolic Encephalopathy (Diffuse Brain Dysfunction)
The phylogenet ically new er brain st ruct ures t end t o be more sensit ive t o
met abolic injury. This holds t rue alt hough t he t arget of various met abolic
abnormalit ies or t oxic agent s may vary slight ly. For inst ance, carbon monoxide
poisoning causes pallidal necrosis in addit ion t o t he w idespread cort ical damage
expect ed f rom any hypoxic insult . Funct ions subserved by complex polysynapt ic
pat hw ays are aff ect ed earlier by met abolic dist urbances t han t hose mediat ed by
a f ew neurons. Theref ore, higher cort ical f unct ions and at t ent ion succumb early
t o met abolic insult s, w hereas t he pupillary light ref lex remains t o t he brink of
brainst em deat h. Survival of ot her f unct ions ranges bet w een t hese t w o ext remes.
By t he t ime decerebrat e post uring appears, t he corneal ref lexes may be severely
depressed, but some eye movement s may be elicit ed by t he doll's eye maneuver
or caloric st imulat ion.
Asymmet ric motor f i ndi ngs speak against t he diagnosis of met abolic
encephalopat hy. How ever, dow nw ard deviat ion of t he eyes may be occasionally
associat ed w it h hepat ic encephalopat hy [65] and hemiparesis w it h hypoglycemia.
Some t oxic subst ances, like et hylene glycol, produce f ocal brain injuries w it h t he
corresponding neurologic localizing f indings [95] . Focal seizures are common in
met abolic encephalopat hies, part icularly t hose coursing w it h t he breakdow n of
t he blood–brain barrier, such as eclampsia, malignant hypert ension, and acut e
int ermit t ent porphyria [85] .
Toxic-met abolic disorders of t en induce abnormal movements (t remor, ast erixis,
myoclonus, and seizures) t hat seldom accompany f ocal st ruct ural lesions of t he
brain. But because t hese t w o t ypes of et iologic f act ors of t en coexist , t he
diagnost ic specif icit y of t hese abnormal movement s is f ar f rom absolut e.
The tremor of met abolic encephalopat hy is coarse and irregular and ranges f rom
8 t o 10 cycles per second. I t s amplit ude is great est w hen t he pat ient holds his
hand out st ret ched, but in less responsive pat ient s it may be f elt by holding t he
pat ient 's f ingers ext ended.
Asteri xi s is a sudden, brief loss of post ural t one t hat is t ranslat ed int o a f lapping
movement
w hen t he hand is held in dorsif lexion at t he w rist and t he f ingers are ext ended
and abduct ed. This hand post ure requires some cooperat ion f rom t he pat ient , but
ast erixis can also be elicit ed by passively ext ending t he pat ient 's f ingers and
w rist . Ast erixis at t he hip joint s can be elicit ed by a maneuver in w hich t he hips
are passively f lexed and abduct ed at approximat ely 60 t o 90 degrees bet w een
t he t highs [101] . This ast erixis seems t o be provoked by involunt ary cont ract ion
of t he hip adduct ors against gravit y and may be especially prominent in
st uporous pat ient s w it h hepat ic encephalopat hy. Ast erixis is present w it h slight
st upor and w anes as coma deepens. Uni l ateral asteri xi s may appear w hen a
t oxic encephalopat hy coexist s w it h a st ruct ural lesion of t he mot or pat hw ays t hat
project t o t he limb w it h ast erixis. Unilat eral ast erixis may be seen cont ralat eral
t o lesions of t he mesencephalon, vent rolat eral t halamus, primary mot or cort ex,
or pariet al lobe [15, 26, 31, 87, 99, 123, 154] or ipsilat eral t o lesions of t he
pons or medulla [110] . Episodes of lapses of post ural cont rol by t he ret icular
f ormat ion may be responsible f or midbrain ast erixis. For t his reason, midbrain
ast erixis has been considered a “segment al f orm of drop at t ack” [12] .
O ccasionally, bilat eral ast erixis may occur w it h bilat eral lesions of t he midpons
[ 12] or w it h bilat eral mesencephalic lesions [69] .
Mul ti f ocal myocl onus consist s of sudden, nonrhyt hmic t w it ching t hat aff ect s f irst
one muscle, t hen anot her, w it hout any specif ic pat t ern except a t endency t o
involve t he f acial and proximal limb musculat ure. The causes of mult if ocal
myoclonus include uremic and hyperosmolar–hyperglycemic encephalopat hy,
carbon dioxide narcosis, and a large dose of int ravenous penicillin [44] .
G eneral i zed myocl onus, usually post anoxic, mainly involves t he axial
musculat ure, w hich cont ract s suddenly, making t he pat ient jump w it h a cert ain
periodicit y [55] . I t may also appear as irregular brief jerks in bot h f ace and
limbs. The myoclonus, of t en st imulus sensit ive, is most prominent in t he f irst
post resuscit at ion day and t ends t o abat e spont aneously in subsequent days. The
pat ient s of t en have a burst -suppression pat t ern on EEG s and cerebral edema or
inf arct s on CT scan or MRI . Severe anoxic cort ical and brainst em damage are
t he most common pat hologic correlat es of generalized myoclonus (also called
myocl oni c status), w hich carries a poor prognosis [107, 180] .
I n addit ion t o symmet ric mot or f indings, hypervent ilat ion or hypovent ilat ion and
t he presence of acid–base imbalance are charact erist ic of met abolic coma.
Respirat ory depression of t en f ollow s int oxicat ion w it h opioid subst ances and
darkens it s prognosis [52] .
Supratentorial Structural Lesions

To cause coma, suprat ent orial lesions must aff ect bot h cerebral hemispheres
(e. g. , massive bihemispheric or bilat eral t halamic inf arct ion). The clinical
present at ion of t hese lesions, and of subarachnoid hemorrhage, resembles in
many aspect s t he present at ion of met abolic disorders. For inst ance, in
post operat ive coma, of t en chalked t o met abolic causes, ischemic brain lesions
may play a major role [42] . How ever, many cerebral inf arct s, even w hen
bilat eral, are of t en st aggered, appear more abrupt ly t han met abolic
encephalopat hies, and cause asymmet ric mot or signs, at least early in t heir
course. Sudden onset of severe headache (“thundercl ap headache”) and signs of
meningeal irrit at ion separat e subarachnoid hemorrhage f rom met abolic
encephalopat hies [81] . Pit uit ary apoplexy can also present w it h headache and
st upor [157] .
The f ollow ing discussion deals mainly w it h suprat ent orial lesions t hat cause
mass eff ect and secondarily impair consciousness by compressing t he
diencephalic and upper brainst em st ruct ures. Prime examples are hemispheric
t umors, subdural or int racerebral hemorrhage, and massive inf arct s. When t he
int racranial pressure of t he suprat ent orial compart ment reaches a cert ain level,
t he brain subst ance is squeezed t hrough t he t ent orial opening. O ccasionally, t he
syndrome of t ranst ent orial herniat ion may occur w it h minimal dow nw ard
displacement of t he upper midbrain [131] . Depending on t he suprat ent orial
locat ion of t he mass and t he size of t he t ent orial opening, eit her of t he t w o
clinically relevant syndromes may result : lat eral (uncal) herniat ion or cent ral
(t ranst ent orial) herniat ion.
Lateral Herniation
I n pat ient s w it h a w ide t ent orial opening, l ateral extracerebral or temporal l obe
masses push t he mesial t emporal lobe (uncus ant eriorly, parahippocampal gyrus
post eriorly) bet w een t he ipsilat eral aspect of t he midbrain and t he f ree edge of
t he t ent orium (Fig. 22-6). As t he t ongue of herniat ed t issue compresses t he t hird
cranial nerve and post erior cerebral art ery dow nw ard, t he ipsilat eral pupil
becomes progressively dilat ed and responds sluggishly t o light (Fig. 22-7). This
st age can be rat her brief and, depending on t he size and acut eness of t he
lesion, it may last f rom a f ew minut es t o several hours. Prompt recognit ion and
removal (of t en surgical) of t he off ending agent is mandat ory at
t his st age because t he usual progression is deadly. The post erior cerebral
art ery, pinched against t he t ent orial edge by t he herniat ed parahippocampal
gyrus, becomes occluded, giving rise t o a hemorrhagic mesial occipit al inf arct .
The herniat ed hippocampus also pushes t he midbrain against t he rigid edge of
t he dura on t he opposit e side of t he t ent orial opening. This rigid st ruct ure carves
out a not ch (Kernohan's notch) in t he lat eral aspect of t he midbrain, int errupt ing
t he cerebral peduncle (part icularly t he f ibers t hat project t o t he leg) on t he side
opposit e t he original t emporal lobe
lesion (Fig. 22-6). This result s in hemiparesis ipsilat eral t o t he original lesion
(Kernohan's not ch phenomenon). I f misint erpret ed, such hemiparesis may prove
t o be a f alse localizing sign. Theref ore, w hen a dilat ed pupil and hemiparesis
appear ipsilat erally, t he original lesion is likely t o be on t he side of t he abnormal
pupil.
FI G URE 22-6 Lat eral t ranst ent orial herniat ion: (A) basal view, (B) coronal
view. I n t his example, a subdural hemat oma is causing a marked shif t of t he
midline st ruct ures and herniat ion of t he parahippocampal gyrus t hrough t he
t ent orial not ch. O cclusion of t he post erior cerebral art ery, w hich is pinched
bet w een t he herniat ed hippocampal t issue and t he rigid end of t he t ent orium,
has result ed in medial t emporo-occipit al inf arct ion. The midbrain is
compressed against t he cont ralat eral f ree t ent orial edge, causing a
lacerat ion of t he crus cerebri (Kernohan's not ch). St ret ching of t he slender
perf orat ing branches of t he basilar art ery has produced pet echial
hemorrhages in t he t egment um of t he midbrain (Duret 's hemorrhages).
FI G URE 22-7 Clinical f indings w it h lat eral t ranst ent orial herniat ion.
(Reproduced f rom McNealy DE, Plum F. Brainst em dysf unct ion w it h
suprat ent orial mass lesions. Arch Neurol 1962; 7: 10 . Copyright 1962,
American Medical Associat ion. ).
At t his point , ant eropost erior elongat ion and dow nw ard displacement of t he
midbrain have already caused t earing of t he paramedian perf orat ing vessels t hat
f eed t he midbrain t egment um. The consequent inf arct ion and hemorrhages
(Duret's hemorrhages) t hat involve t his st ruct ure render recovery almost
impossible. The pupil t hat w as larger may become a lit t le smaller as t he
sympat het ic pat hw ay is damaged in t he midbrain, w hereas t he ot her pupil
becomes midsize and unresponsive. O culomot or paresis appears f irst in t he eye
originally involved and short ly af t erw ard in t he ot her eye. Abduct ion may remain
as t he only elicit able eye movement .
Many causes of lat eral herniat ion, such as hemat omas, can be surgically
t reat ed. How ever, pat ient s w it h a combinat ion of absent pupillary, corneal, and
oculocephalic ref lexes and ext ensor post uring bef ore craniot omy have a very
poor prognosis [117] . Survivors of t ent orial herniat ion may be lef t in a locked-in
or chronic veget at ive st at e [64] and may demonst rat e oculomot or nerve
dysf unct ion, int ernuclear opht halmoplegia, vert ical gaze paresis, pret ect al signs
[ 18, 63] , homonymous hemianopsia or blindness [59] , parkinsonism and ot her
ext rapyramidal syndromes, or spast ic limb w eakness [18] . A proport ion of t hese
pat ient s may recover, part icularly w it h aggressive t herapy [116, 179] . Bilat eral
visual loss af t er t ent orial herniat ion is likely due t o bilat eral post erior cerebral
art ery compression or st ret ch result ing in bilat eral occipit al inf arct ion; how ever,
occasional pat ient s develop opt ic at rophy, indicat ing t hat a pregeniculat e
mechanism may also be operant [59] .
Central Herniation
Unlike t emporal masses, f ront al, pariet al, or occipit al masses f irst compress t he
diencephalon, w hich, as t he suprat ent orial pressure increases, shif t s dow nw ard
and buckles over t he midbrain. Subsequent f lat t ening of t he midbrain and pons in
t he rost rocaudal direct ion causes elongat ion and rupt ure of t he paramedian
perf orat ing art eries f eeding t hese st ruct ures, result ing in inf arct ion and
hemorrhages (Duret 's) in t he t egment um of t he midbrain (f irst ) and pons
(af t erw ard) (Fig. 22-8).
Paralleling t he pat hologic changes of cent ral herniat ion, t he clinical pict ure
ref lect s an orderly rost rocaudal progression of brainst em damage. The
charact erist ic evolut ion of t he clinical pict ure has been t ermed t he central
syndrome of rostrocaudal deteri orati on [ 114] . Descript ion of t his syndrome
enables one t o review t he charact erist ic clinical f indings w it h lesions at t he
diff erent levels of t he brainst em (Fig. 22-9). I n acut e illness, MRI changes of
brain herniat ion (incisural or f oramen magnum) t end t o parallel t he clinical signs
of brain herniat ion; in chronic cases, clinical scans and MRI correlat e less w ell,
w it h t he MRI somet imes revealing major degrees of anat omic herniat ion w ell in
advance of clinical abnormalit ies [122] .
FI G URE 22-8 Cent ral t ranst ent orial herniat ion. A: Normal saggit al sect ion of
t he brainst em. Not e t he vascular perf orat ors, branches of t he basilar art ery.
B: Mass eff ect f rom a high pariet al t umor, result ing in dow nw ard
displacement and superoinf erior f lat t ening of t he midbrain and upper pons.
The increased cross-sect ional diamet er of t hese st ruct ures is at t ended by
st ret ching and rupt ure of t he perf orat ors, w it h subsequent hemorrhages in
t he t egment um of t he midbrain and upper pons.
Early Diencephalic Stage
I mpaired at t ent ion and somnolence appearing in a pat ient w it h a suprat ent orial
mass usually herald t he beginning of t his st age. The respirat ory pat t ern is
normal but is punct uat ed by deep sighs and yaw ns. I n periods of great er
somnolence, t he pupils become t iny but react t o light , w hereas t he eyes become
slight ly divergent , moving slow ly f rom side t o side (roving eye movement s).
At t empt s t o perf orm t he doll's eye maneuver may provide enough of a st imulus t o
aw aken t he pat ient , and quick eye movement s (saccades) are t hen elicit ed
rat her t han t he slow adversive movement s of t he oculocephalic ref lex. For t he
same reason, caloric st imulat ion may induce nyst agmus. The pat ient resist s
passive mot ion of t he limbs (paratoni a), may have grasp ref lexes, and brushes
off appropriat ely any noxious st imulus. Plant ar responses are usually bilat erally
ext ensor.
Late Diencephalic Stage

At t his st age t he pat ient cannot be aroused. Cheyne-St okes respirat ion replaces
normal breat hing. The pupils remain small and react ive. Roving eye movement s
have disappeared, but t he doll's eye maneuver or caloric st imulat ion easily elicit s
f ull and conjugat e deviat ion of t he eyes. As t he process advances, how ever,
t ect al dysf unct ion may result in rest rict ion of upw ard gaze. Light painf ul st imuli
f ail t o elicit any response; heavier ones may induce decort icat e post uring, w hich
appears earlier on t he side of a previous hemiparesis, opposit e t he
suprat ent orial lesion. Plant ar responses are bilat erally ext ensor.
Proper diagnosis and t reat ment at t his st age of t he syndrome of cent ral
herniat ion may st ill result in recovery of neurologic f unct ion. O nce t he clinical
pict ure evolves int o t he next st age (caused by hemorrhages and inf arct ion of t he
midbrain t egment um), t he prognosis is very poor, except in children.
Midbrain–Upper Pons Stage

The pat ient now breat hes rat her quickly and evenly. Temperat ure oscillat ions are
common, and an occasional pat ient may develop diabet es insipidus because of
st ret ching of t he median eminence of t he hypot halamus. The pupils become
midsized, unequal, and irregular, of t en pear-shaped and eccent ric. Terminally,
generalized anoxia causes a syst emic release of epinephrine, and t he pupils may
be t ransient ly dilat ed. The doll's eye maneuver and caloric t est ing elicit
rest rict ed or no vert ical eye movement s. The eyes of t en move disconjugat ely in
bot h t he horizont al and t he vert ical planes. Bilat eral
impairment of adduct ion may ref lect dysf unct ion of bot h t hird nerve nuclei, of t he
medial longit udinal f asciculi, or bot h. Noxious st imuli give rise t o decerebrat e
post uring.
Lower Pontine Stage
Respirat ion becomes quicker and shallow er. Apneust ic breat hing, common w it h
primary ischemic lesions of t his area, is inf requent in pat ient s w it h t ranst ent orial
herniat ion, perhaps because more medially locat ed st ruct ures are pref erent ially
damaged. The pupils remain unchanged f rom t he previous st age, but eye
movement s are now unobt ainable. Decerebrat e rigidit y decreases. Plant ar
st imulat ion may elicit not only bilat eral Babinski's signs but also w it hdraw al of
t he legs, w it h f lexion at t he knee and hip.
Medullary Stage
I n t his agonal st age, at axic breat hing soon gives w ay t o apnea. The blood
pressure drops, and t he pulse becomes irregular [121] .
Large acut e suprat ent orial lesions, part icularly massive int ravent ricular
hemorrhage, may cause a quick decompensat ion of brainst em f unct ion, leading
t o respirat ory f ailure w it hout t he st epw ise progression described in t he
preceding t ext . Smaller int ravent ricular hemorrhages may impair ref lex eye
movement s in t he horizont al and vert ical planes alt hough t he pat ient 's level of
consciousness is only mildly depressed. This phenomenon may be secondary t o
t he act ion of t he blood on t he f loor of t he f ourt h vent ricle and may have played a
role in an unusual case of t ransient locked-in syndrome w it h int ravent ricular
hemorrhage and a t ranst ent orial herniat ion [179] .
Alt hough t he clinical det eriorat ion of pat ient s w it h suprat ent orial masses of t en
f ollow s t he pat t ern described in t he preceding t ext , early depression of t he level
of alert ness in pat ient s w it h an acut e hemispheric mass may be relat ed more t o
t he dist ort ion of t he brain by horizont al rat her t han vert ical displacement of brain
t issue [127] . Ropper show ed t hat a horizont al pineal body shif t of 0 t o 3 mm
f rom t he midline w as associat ed w it h alert ness, 3 t o 4 mm w it h drow siness, 6 t o
8. 5 mm w it h
st upor, and 8 t o 13 mm w it h coma [127] . Wit h ext rat emporal masses, t he

perimesencephalic cist ern w as of t en w idened, rat her t han f illed by herniat ed
medial t emporal lobe. O n coronal MRI , horizont al displacement of t he midline of
t he brain at t he level of t he incisura correlat ed bet t er t han vert ical displacement
w it h t he level of alert ness [129] . These st udies do not disprove t hat
ant eropost erior elongat ion of t he midbrain, w it h subsequent ischemia of t he
midbrain t egment um, may play a role in t he genesis of coma and subsequent
brainst em det eriorat ion, as described in t he preceding t ext .
FI G URE 22-9 Clinical f indings w it h cent ral t ranst ent orial herniat ion. (Modif ied
f rom McNealy DE, Plum F. Brainst em dysf unct ion w it h suprat ent orial mass
lesions. Arch Neurol 1962; 7: 10 . Copyright 1962, American Medical
Associat ion. )
As f ar as t he prognosis of lobar hemorrhages is concerned, a G lasgow Coma

score of <14 predict s det eriorat ion [37] . I nit ial CT scan charact erist ics
predict ive of det eriorat ion include hemorrhage volume >60 mL, shif t of t he
sept um pellucidum, eff acement of t he cont ralat eral ambient cist ern, and w idening
of t he cont ralat eral t emporal horn [37] . Deeper put aminal hemorrhages f are
w orse w hen accompanied by hydrocephalus and t he pat ient has a G lasgow
Coma Scale score <8 [112] . The G lasgow Coma Scale is w idely used [158] , but
a new scale, Full O ut line of Unresponsiveness (FO UR), bet t er predict s t he
out come of t he more severely impaired pat ient s [175] .
Some pat ient s develop severe brain edema and coma af t er minor head t rauma
w it h a lucid int erval. A dist urbance of ionic channels has been suspect ed because
t his syndrome is more f requent in f amilies w it h f amilial hemiplegic migraine,
know n t o be associat ed w it h abnormalit ies of t he calcium channel. An S218L
mut at ion in t he CACNA1A calcium channel has been report ed in some of t hese
pat ient s [68] .
Fal se l ocal i zi ng si gns w it h suprat ent orial masses may mislead t he observer
about t he hemisphere involved (e. g. , hemiparesis ipsilat eral t o t he lesion due t o
Kernohan's not ch) or f alsely localize t he primary process t o t he post erior f ossa.
The lat t er occurs mainly w it h lesions locat ed in t he midline (e. g. , hydrocephalus)
or in areas of t he f ront al and t emporal lobes t hat are clinically “silent . ”
Ext racerebral lesions (e. g. , subdural hemat oma) in t he elderly may behave in a
similar manner. These lesions f ail t o cause f ocal def icit s but raise t he pressure
of t he int racranial cont ent s and produce cranial nerve dysf unct ion t hat may be
mist aken f or evidence of a post erior f ossa lesion. Sixt h nerve palsy and
papilledema are t he commonest f alse localizing signs, but ot her
opht halmoplegias, t rigeminal neuralgia or numbness, unilat eral or bilat eral
deaf ness,
f acial palsy, and even w eakness in t he dist ribut ion of t he nint h t o t w elf t h cranial
nerves may appear as a consequence of raised int racranial pressure w it h a
suprat ent orial lesion.
Subtentorial Structural Lesions

Dest ruct ive lesions (e. g. , inf arct s, small hemorrhages) of t he brainst em can be
easily localized clinically. Compressive lesions t hat cause coma t end t o be
associat ed w it h brisk involvement of t he cerebellum or t he f ourt h vent ricle.
Cerebellar hemorrhage is t he prime example [181] . Early in t he clinical course,
occipit al headache, vomit ing, and at axia are usually prominent . I n t he process of
rost rocaudal det eriorat ion charact erist ic of dow nw ard t ranst ent orial herniat ion,
all t he st ruct ures at a part icular brainst em level t end t o be aff ect ed at t he same
t ime. This does not happen w it h compressive lesions of t he post erior f ossa.
Unless massive, t hese lesions aff ect one level more t han ot hers, of t en
asymmet rically, giving rise t o pref erent ially unilat eral brainst em and cerebellar
signs.
Lesions t hat compress t he upper brainst em may cause upw ard t ranst ent orial
herniat ion of t he t ect um of t he mi dbrai n and of t he ant erior cerebellar lobule,
giving rise t o signs of midbrain dysf unct ion w it h coma, hypervent ilat ion, f ixed
pupils, and vert ical opht halmoplegia. Low er lesions impinge on t he ponti ne
t egment um, causing somnolence, pinpoint pupils t hat react briskly t o light ,
oculoparet ic nyst agmus on lat eral gaze, and t runcal at axia. Appendicular at axia
may be so mild as t o pass unnot iced. As pont ine f unct ion becomes w orse,
horizont al gaze disappears and cannot be elicit ed w it h t he doll's eye maneuver
or caloric t est ing, w hereas impairment of vert ical eye movement s clearly lags
behind. Wit h low er lesions t hat impinge mainly on t he medul l a, respirat ory at axia
evolving t o apnea and circulat ory abnormalit ies precede changes in t he level of
alert ness. The medulla is part icularly resist ant t o inf arct ion, spont aneous
hemorrhages, and even t raumat ic lesions [174] . How ever, it is pref erent ially
aff ect ed in List eria monocyt ogenes rhombencephalit is [167] and in Leigh's
disease [137, 182]
Det eriorat ion w it h pont ine hemorrhages depends on t he cause of t he lesion.
Bleeding f rom cavernous angiomas has a much bet t er prognosis t han
hypert ensive hemorrhage [118] . Prognost ic f act ors w it h cerebellar hemorrhages
are more import ant f or surgical decision-making. Anat omic f indings t hat predict
det eriorat ion w it h cerebellar hemorrhage include displacement of t he f ourt h
vent ricle, brainst em def ormit y, hydrocephalus, and compression of t he basal
cist erns [67, 152] . I n some series, a hemat oma size of more t han 3 cm also
w orsens prognosis [152] . Clinically, pat ient s w ho have abnormal corneal and
oculocephalic responses, a G lasgow Coma Scale score <8, and mot or response
less t han localizat ion t o pain f are poorly [152] .
Mass lesions in t he post erior f ossa may cause dow nw ard herniat ion of t he
cerebellar t onsils t hrough t he f oramen magnum, w it h subsequent inf arct ion of t he
t onsils, medulla, and even upper cervical spinal cord. G eneralized anoxia and
circulat ory f ailure consequent t o medullary dysf unct ion play a role in t he genesis
of t hese inf arct s.
When pat ient s w it h preexist ing brainst em lesions, most of t en f rom st rokes or
mult iple sclerosis, suff er an anoxic or met abolic insult , t hey may lose all
brainst em ref lexes t ransient ly [125] . The diagnosis of irreversible damage of t he
brainst em has t o be done more caut iously in t hese pat ient s.
Psychogenic Unresponsiveness
The pat ient may hold t he eyes f orcibly closed and resist eyelid opening or may
keep t he eyes open in a f ixed st are, int errupt ed by quick blinks. The pupils,
w hich are of normal size and posit ion, react t o light unless a cycloplegic drug
has been inst illed int o t hem. The doll's eye maneuver elicit s random or no eye
movement s. Caloric t est ing is more helpf ul because it gives rise t o classic
vest ibular nyst agmus w it h a quick component t hat requires act ivit y of t he f ront al
eye f ields. This quick component is, conversely, absent in comat ose pat ient s.
Muscle t one and ref lexes are normal. The pat ient may hypervent ilat e or breat he
normally. Psychogenic unresponsiveness of t en recurs and as such is f requent ly
misdiagnosed as an epilept ic or migranous disorder [27, 142, 147] .
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Authors:

Brazis, Paul W. ; Masdeu, Jose C. ; Biller, Jose

Jose C. Masdeu MD, PhD

José Biller MD, FACP, FAAN, FAHA

Preface to the Fifth Edition

Preface to the Fourth Edition

Preface to the First Edition

A Brief History of Localization: Aphasia as an Example

From t he t ime of Hippocrat es, in ancient G reece, it w as document ed t hat injury

During t he course of our st udy of brains of pat ient s w it h

I n t he f ew years af t er Broca's remarkable st at ement s, know ledge about t he

The w hole area of convolut ion encircling t he Sylvian f issure,

FI G URE 1-1 Wernicke's diagram of t he language areas. I n t he original, t he

The branch of t he art ery of t he lef t Sylvian f issure, running

Wernicke's diagram of t he language areas is illust rat ed in Figure 1-1.

The brain lesion–behavior approach has been complement ed

Clinical Diagnosis and Lesion Localization

1. Recognit ion of impaired f unct ion

t he hand may also have at rophy of t he muscles in t he t henar eminence and a

Localization of Lesions of The M otor System

Motor Signs and Symptoms and Their Localization

TABLE 1-1 M edical Research Council's Scale for

0 No muscle contraction visible

1 Flicker or trace of contraction, but no movement

Active joint movement when effect of gravity is

3 Active movement against gravity

Active movement against gravity and

is associat ed w it h t he presence of pat hologic ref lexes and signs, such as t he

presence of purposef ul movement s of t he hand associat ed w it h rest , post ural

The Localization of Sensory Abnormalities

across t he cord midline t o ascend and join t he medial lemniscus in t he medulla.

From t he t halamus, t he sensory impulses are conveyed mainly t o t he

Sensory Signs and Symptoms and Their Localization

Localization of Postural and Gait Disorders

TABLE 1-2 The Localization of Lesions Affecting the

Sensory symptoms mainly in the

Usually distal symmetric sensory

Similar to dorsal root lesion

Irritative symptoms (e.g., radicular

Dorsal horn or central gray matter

Similar to the sensory changes

Similar to the sensory changes

Lesion of VPL nucleus results in

Circumscribed lesion of the

CN = cranial nerve; VPL = ventral-posterior-lateral.

Neural Structures Controlling Posture and Gait

Sensory and Lower Motor Gait Disorders

Simpler Gait Disorders of Central Origin

Cerebellar Ataxic Gait

disease diff ers f rom t he gait of pat ient s w it h t he at ypical parkinsonian

Choreic, Hemiballistic, and Dystonic Gaits

Complex Gait Disorders of Central Origin

The Cautious Gait

Disequilibrium With “Automatic Pilot” Disorder

1. Basal gangl i a l esi ons. Early disequilibrium charact erizes progressive

Disequilibrium may also be prominent in pat ient s w it h hydrocephalus and w it h

Isolated Gait Ignition Failure

Disequilibrium and Disorganized Gait

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