Neuroanatomy Notes

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Neuroanatomy notes
MBBS (Osh State University)
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Dr. Najeeb Lecture Notes- Neuro
Transcribed and compiled by Neil Parikh

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Table of Contents
I. Neuromuscular Junction (NMJ) 2

II. Overview of Neuroanatomy 23
III. CSF & Ventricular System 26
IV. Blood Supply to CNS 43
V. Meninges & Types of Intracranial Hemorrhage 55
VI. Cranial Nerves 66
VII. In Depth Cranial Nerves 89
VIII. Herniation 102
IX. Organization of Brain + Epilepsy/Seizure 104
X. Tracts of the Spinal Cord 109
XI. Basal Ganglia 126
XII. Brainstem Basics— Midbrain, Pons, Medulla 129
XIII. Vestibular System 132
XIV. Auditory System 137
XV. Visual System
XVI. Cerebellum
XVII. Spinal Cord Lesions
XVIII.
XIX.
XX.

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I. Neuromuscular Junction
Resting Membrane Potential
Resting membrane potential— transmembrane potential which does not fluctuate

and are present in almost all cells
Action potential— fluctuating electrochemical changes across the cell membranes,
which are produced only in neurons and muscle cells
Types of channels
 Ungated channels— also called “leaky channels”; always open
 Gated Channels
o Voltage-gated— need to reach certain voltage to open, otherwise
closed
o Ligand-gated— need to bind certain ligand to open, otherwise closed
Evolution states that unicellular life began in the ocean, which is salty  all cells
now want to keep salt out (surrounding them just like the ocean)
 N/K ATPase Gene which every cell has  Na/K ATPase protein (pump)
o 25% of the chemical energy that your body is using right now is used
to maintain this gradient
o Remember that it extrudes 3Na+ but takes in 2K+  net loss of
cations
 This means that cells are becoming more electronegative
 Electrogenic pump— any pump which works across the
membrane and during its function produces an electric
imbalance
o This electronegativity now established in the cell is only -5mV (NOT
resting membrane potential, which is around -90mV)
 Now, there are leaky channels for K+ present in the cell membrane
o K+ wants to leave since more K+ inside than outside (concentration
gradient) but electronegativity of the cell wants to keep it in since it
is a cation (electrical gradient)
o Net electrochemical force is outward since the electronegativity of the
cell is only around -5mV
o However, the cell begins progressively more electronegative, since K+
moves out but anions are left behind
 Diffusion potential is the electronegativity of the cell which is
developing due to outward diffusion of cations (K+) and
retention of anions
 As more K+ diffuses out, cell develops higher diffusion
potential
 However, as more K+ leaves and the electrical gradient increases (due to
more electronegative cell interior), it becomes more difficult for K+ to leave
o At a certain point the K+ concentration gradient and electrical
gradient are opposing each other equally, so the # of K+ ions moving

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in out via the concentration gradient = # of K+ ions moving in via the

electrical gradient
 This potential when K+ is in equilibrium is called equilibrium
potential
Resting Membrane Potential 2
Normal K+ concentration:
 Outside the cell is 4mmol/L
 Inside the cell is 140mmol/L
Another name for equilibrium potential is Nernst potential

 Aka diffusion potential for K+ at which net movement is zero, in spite of the
fact that the membrane is permeable to K+
 Nernst potential for K+ is -85mV
Second cell (last one was permeable to K+, this one permeable to Na=)
 Na+ wants to move in due to concentration gradient established by Na/K
ATPase
o However, electrical gradient opposes it (wants it to leave)
 Electropositivity developing due to inward diffusion of Na+ is called the Na+
diffusion potential
o Eventually, this diffusion gradient can oppose the concentration
gradient, which means that the membrane has achieved equilibrium
potential for Na+
 Equilibrium potential for Na+ is around +65mV inside
Equilibrium potential of human cells

 If all cells in the body are permeable only to K+, they will have an equilibrium
potential that is very negative (-85mV)
o If all cells in the body are permeable only to Na+, they will have an
equilibrium potential that is very positive (+65mv)
 Human cells have membrane potential of around -70 to -90mV when at rest

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o Scientists called this potential resting membrane potential
 This is the potential difference across cell membranes of

-80mV (inside)
 This is clearly closer to K+ equilibrium potential, meaning that our cells are
freely permeable to K+ and not freely permeable to Na+
 Inner part of the cell has a negative resting potential, and is negatively
polarized
What is the role of Na/K ATPases in resting membrane potential

 The direct contribution of Na/K ATPases is very little, since the resting
membrane potential is mainly formed from K+ efflux
 However, they have a very powerful indirect role!
o The reason K+ can efflux is because there was a concentration
gradient favoring their efflux
o Na/K ATPases are what created this gradient
Na+ channels in neuronal cell membranes

 If these are activated, Na+ will rush in (since there are no leak channels for
Na+ normally present, and it has a very favorable concentration gradient into
the cell)
o Note— these are special Na+ cells only present in neurons and muscle
 Na+ will do its best to reach its own equilibrium potential (+65mV)
o BUT, before it reaches its equilibrium potential, the door shuts (aka
the inactivation gate closes)
o However, enough of it influxes that the once negatively polarized
membrane loses its polarity
Resting Membrane Potential 3
Nernst Equation: E = RT log [Co]

zF [Ci]
R= universal gas constant

T = Temp (kelvin)
Z = charge of ion
F = Faraday’s constant
Co = concentration of ion outside the cell
Ci = concentration of ion inside the cell
Nernst equation tells you the membrane potential at which net ion movement will
be zero (in spite of the fact that the cell membrane is still permeable to that ion)
 i.e. E tells you the equilibrium membrane potential
Effect of concentrations on the concentration gradient (WHY is log (Co/Ci important)
 If you increase the concentration of K+ inside the cell, then the concentration
gradient favoring K+ efflux will also increase

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o This means that equilibrium potential will change and become more
negative! Ex: -95mV
 If you increase the concentration of K+ outside the cell, then the
concentration gradient favoring K+ efflux will decrease
o This means that equilibrium potential will change and become more
positive! Ex: -75mV
Calculation
 Crossing out constants  (-60mV/z) log([Ci]/[Co])
o Aka constants = -60mV
 Example
o Co Na+ is 150mM/L, Ci Na+ is 15mM/L
o = -60mV/1 (Na+ is monovalent) x log(15/15o)
o -60mV x -1 = +60mV
o So only at +60mV will Na+ influx be stopped, even if the membrane is
still permeable to Na+
The cell membrane may be under the effect of multiple ions and their movement
 Cl- Nernst potential is -85mV, which happens to be around the same of K+
Nernst potential
o This means that net movement of Cl- will be very low under resting
membrane potential, normally -90mV
o Also, they do not enter because electrical gradient is against them
(-90mV is more negative than Cl- resting potential of -85mV)
 What will be the voltage across the membrane when there are multiple ions
with slightly different permeabilities?
o This means we need to sum the Nerst potentials of Cl-, K+, and Na+
o This equation is called the Goldman Equation:
Remember that k (constant) is -60mV, which is a calculated version of RT/F
Note— in a resting situation, the permeability of Na+ is zero, so it can be cancelled

out from the equation (as can Cl- since it does not move at rest)
 So essentially, the Goldman equation reduces to a K+ Nernst equation at rest
Clinical applications
 K+, Na+, Cl- move between blood and ECF (plasma + interstitial fluid)
o So ECF ion concentration can be determined by the concentration of
that ion in the blood
o Note— these ions do not move freely, and are well regulated

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 Action potential— in excitable cells like neurons and muscles, when the
resting membrane potential reached the threshold membrane potential,
suddenly, voltage-gated cation channels open (Na+ or Ca2+)
o At that point, many cations rush into the cell
o If you want to stimulate the cell, that means you want to depolarize it
 In order for depolarization to occur, you must take the cell’s
resting membrane potential to threshold membrane potential
(exactly how this happens is discussed in action potential
lecture)
 What happens to relationship of resting membrane potential and threshold
membrane potential with changes in K+ concentration in the blood
o Lets say you are taking wasting diuretics like thiazide, and K+ goes
into urine  K+ concentrations will fall outside the cell
 So concentration gradients which drive K+ outside the cell
 This means that is hypokalemia, an excessive amount of K+ is
diffusing out of the cell
  hyperpolarization (inside of cell becomes
excessively negative, in this case due to increased K+
efflux)
o This makes it harder to reach threshold
potential, so electrical excitability is altered
o Let’s say someone develops Hyperkalemia (increased K+ in the
blood); simplest cause is cell death (crush injury, burns, septicemia,
etc.) since massive amounts of K+ will be released into the blood (also,
normal kidney compensation via urinary excretion may be impaired
since substances which may be toxic to the kidney may be released
from cells).
 Normal value of K+ in the blood is 3.5-5.0meQ/L
 Know this value or people may die because of it
 Note— K+ is regulated by the kidneys, so increased
dietary intake will not raise blood K+
o Regulation can handle slight increase/decrease
in blood K+ by decreasing/increasing K+
excretion in urine, respectively
 Another cause of hyperkalemia is acute renal failure
 The most dangerous value that changes is K+ (not
creatinine or urea, which are only markers of kidney
function)
 Resting membrane potential becomes more positive with
hyperkalemia (slightly depolarized)
 It seems that this would make the membrane more
excitable, but actually…
Why hyperkalemia (increased K+ in blood) does not make cell more excitable
 Na+ channels have an activation and inactivation gate

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 If you constantly keep the resting membrane potential too close to the
threshold membrane potential
o You are sending the wrong message to the activation/inactivation
gates, which are supposed to work acutely and shut down
o Na+ channels then permanently close their inactivation gate
 Activation gate is already close so that means both are closed
 This means that even if the threshold potential is reached, the
inactivation gate is still closed!
 To return to the normal state, we must return to a resting
membrane potential of -85mV
 So essentially, very high K+ (hyperkalemia) also causes difficulty in exciting
cells
Summary of two different mechanisms of K+ affecting excitability of cells

 Hypokalemia— resting membrane potential is farther from threshold so it
takes extra effort
 Hyperkalemia— more K+ outside  lower rate of K+ efflux  resting
membrane potential chronically near threshold membrane potential  most
Na+ channels are in inactivated state (inactivating gates permanently closed)
 more difficult to excite cells  cardiac neuromuscular, cardiac, cellular
function is disrupted
Last Question: Hypernatremia vs. Hyponatremia

 Normal value of Na+ in blood = 135-145 mEq/L
 Resting membrane potential is not affected by Na+
o Remember that the cell is not permeable to Na+ at rest!

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Action Potentials
Action potentials— electrochemical fluctuations in the cells membranes of

excitable cells, which rapidly propagate
 Example: dorsal root ganglion has a unipolar neuron, with the cell body in
dorsal root ganglion, a central process connecting to the spinal cord, and a
peripheral process which is the sensory component
Now let’s see how touch (conveyed to the sensory neuron) produces an action
potential
 Resting:
o Na/K ATPases are present in all cells including neuronal cells
o Resting cells are permeable to K+ but not permeable to Na+ via K+
leaky channels
 K+ channel continues to leak, developing K+ diffusion potential
until it reaches its equilibrium potential
 Resting value is around -90mV
o Note— membrane may not be 100% permeable to K+, so the cell may
not actually achieve K+ equilibrium potential (may be closer to -
70mV)
 Neuron stimulated by touch:
o The neuron contains mechanically operated Na+ channels (i.e.
touch sensitive)
 Note— when the neuron is at rest (i.e. NOT stimulated by
touch) Na+ does not enter
 However, if stimulated by touch, the membrane is distorted 
Na+ trickles in
 This DOES NOT cause full depolarization
 These are not voltage-gated Na+ channels
o Only at threshold potential do these voltage-
gated Na+ channels open
o Now, when a little touch is applied, not enough Na+ enters to reach
threshold (subthreshold stimulus)
 So voltage-gated Na+ channels do not open
 This potential difference dies out— why?
 As Na+ enters, the electrochemical gradient favors more
K+ to leak to go back to resting membrane potential
o Let’s say a stimulus has enough strength to reach threshold (-60mV)
 Voltage-gated Na+ channels open their activation gates
(remember that at normal resting membrane potential, the
inactivation gate is open, but the activation gate is closed)
 So the activation gate is sensitive to threshold voltage,
and lets in a massive amount of Na+ when it is reached
 The cell quickly becomes less electronegative (i.e. more
positive)

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o We say the membrane is depolarized, since it

has lost its negative polarity!
 However, although Na+ brings the membrane closer to its own
equilibrium potential, it does not reach its equilibrium
potential of +65mV
 Even though the activation gate is open, the inactivation
gate closes, so Na+ influx stops abruptly
 Note— a slight overshoot may occur (membrane
potential above 0mV)
o When Na+ channels are inactivated, they cannot immediately be
stimulated and activated again
 They must go back to resting conformation
o Voltage-gate K+ channels also open, but are slightly delayed
 Note— these channels are different from leaky K+ channels
 They end up opening when Na+ channels become inactivated
 This  K+ efflux (concentration gradient and electrical
gradient favor efflux at this point)
 This is the repolarization phase, when the membrane is more
permeable to K+ than Na+, and even more permeable to K+
than in resting phase
 Note— these voltage-gated K+ channels are also slow to return
to the closed state, which  after-hyperpolarization
 This is followed by return to resting membrane
potential
Propagation of Action Potential
 The Na+ that enters the first portion of the membrane depolarizes the next
segment of the membrane (takes it from resting to threshold)
o Depolarization followed by repolarization (or Na+ influx followed by
K+ efflux) propagates down the membrane
Note— due to Na+ influx an K+ efflux, although the electrical resting membrane
potential is corrected, there is a chemical imbalance that forms, which is corrected
by Na/K ATPases
Action Potentials 2
Local Potential vs. Action Potential

 Local potentials are:
o Non-propagating
o Do not reach threshold (eventually die)
o Graded (may be small or large depending on size of stimulus)
o Can be summed if produced in rapid succession (unlike APs— once
threshold is reached, additional stimulation does nothing)
 Action potentials are:
o Auto-propagating
o “All-or-none”

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 Either it fires or doesn’t based on whether threshold Is reached

or not
o Frequency increases with larger stimulus but amplitude of AP is
constant— i.e. they are stereotyped (rise and fall usually have
approximately the same amplitude and time course)
o Note— this does not mean that neuronal AP and muscle AP are
exactly the same, but that if you were to produce 10 different APs in
muscle they would all be identical (same channels, etc.)
Absolute Relative
refractory refractory
period period
a— changes in membrane potential (mV)

b— changes in relative membrane permeability (P) to Na+ and K+ during an action
potential

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Refractory periods explained by servants (do work, must sit down. Once you give
them an order no matter what you do like yell, scream, or cry, they will complete it.
Once finished, they need to sit down, and won’t do work if you give the next order. If
you really yell at them then they will do it however, so they are relatively refractory)
 Absolute refractory— inactive no matter what the stimulus
 Relative refractory— inactive, but can be activated with large stimulus
o The reason for this is that the cell is hyperpolarized at this point!
 Due to K+ efflux causing after-hyperpolarization
Unusual Situations
 Whichever stimulus you apply, there is no action potential generated
o Example of person with hyperkalemia, whose resting membrane
potential is chronically elevated (since concentration gradient favors
K+ influx)  permanent inactivation of Na+ channels
 Seems counterintuitive because resting membrane potential is
closer to threshold, but remember that the inactivation gate
is closed
 This phenomenon is called accommodation (shown in
unexcitable cells, typically in patients with hyperkalemia)
 Manifests as muscle weakness
 Different than the absolute refractory period because in
that scenario Na+ gates can recover
How does one neuron communicate with another?
 One end of neuron: sensory (i.e. touch)  stimulation of action potential 
propagation to other end of neuron
 Other end of neuron: contains neurotransmitters within vesicles
o Propagating action potential reaches this end  vesicle fusion with
neuronal membrane  neurotransmitter release
o Next neuron: contains receptors to neurotransmitter
 When neurotransmitter released from previous neuron binds
 receptor channel opens (neurotransmitter/hormone/other
substance activated channel, called ligand-gated channels)
 Ex: let us say it is a ligand-gated Na+ channel  action
potential the propagates down this neuron and Na+ influx from
the ligand-gated channel  depolarization
Summary of Energy Transfer
 Mechanical energy (touch) stimulates receptors
 Electrical energy in form of AP propagates down neuron
 Chemical energy in the form of neurotransmitter release
 Chemicals are converted to electrical stimuli at next neuron
Myocardial cells have special electrical windows in between them in the form of gap
junctions, so depolarization spreads rapidly— good example of electrical
stimulation, vs. mechanical stimulation of touch that we discussed earlier

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Action Potentials 3
What factors determine the velocity of action potentials?

1. Thicker diameter = faster; i.e. higher current velocity (lower resistance)
2. Myelination increases velocity significantly
 Example of slow conductor (no myelination)
o One area depolarizes, pushing adjacent area to threshold, which then
depolarizes, and pushes the next area into threshold, and this
continues (like a flame at the end of a firecracker which continues)
 With myelination
o Schwann cells rotate around neuron
 They are essentially forming multiple layers of cell
membranes, which are made up of lipids (sphingomyelin)
 Lipids are a very bad conductors of current
 That essentially insulates that area,
o The sodium that influxed from mechanical Na+ channels (from
original touch stimulus) travel 1-2mm through insulated area and
reach node of Ranvier (gap between myelination) which is very rich
in voltage-gated Na+ channels
 Resting membrane potential richest threshold and fires
 Then, that influx of Na+ travels another 1-2mm down to next
node of Ranvier
o Essentially, the current is only travelling from one node of Ranvier to
the next, cutting down on time taken to influx ions
o This type of conduction is called saltatory conduction (remember,
“saltar” = to jump)
Which sensations travel slowly, which ones travel quickly?
 Dull/chronic pain moves slowly, sharp pain moves quickly
o Dull pain via unmyelinated C fibers
o Sharp pain via heavily myelinated Aδ fibers
 Fine touch moves quickly (typing, pin-prick, etc.)
 Slow sensations:
o Sexual sensations
o Tickling, itching
o Temperature
 First you feel touch of hot oil, then temp; first you feel shower
water hit you then you feel it is very hot
 Slight delay
Advantages of myelination
 Without myelination, there is more depolarization and repolarization, so
Na/K ATPases have to work more
o When myelinated, Na/K ATPases work less (have greater economy)
Note— Schwann cells are also present in unmyelinated axons, but they just don’t
make rotations around them!
 So myelin doe NOT mean Schwann cell, but it means there are multiple layers
of Schwann cell surrounding the axon

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The worst part of Guillain-Barré Syndrome classic cause of PNS demyelination;

ascending paralysis) is that it can demyelinate the nerves supplying respiratory
muscles
Schwann cells vs. Oligodendrocytes

 1 Schwann cell
o Found in PNS
o Can only myelinate 1 axon
 However, 1 axon may be myelinated by more than one
Schwann cell
o Can have improper myelination with 1 Schwann cell surrounded
multiple axons, but none are properly myelinated
 Oligodendrocytes
o Found in CNS
o Can myelinate more than 1 axon
Demyelinating diseases
 It’s important to realize that oligodendrocytes and Schwann cells are entirely
different cells with different proteins and
antigens
 So, if the immune system attacks the PNS
Schwann cells, it will not cross react with
CNS oligodendrocytes
o You will get purely peripheral
demyelinating disease
 Classic CNS demyelinating disease is
Multiple Sclerosis (MS)

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Myasthenia Gravis
Neuromuscular Junction
 Neuromuscular junction = when motor neuron’s nerve endings make a
synaptic connection with voluntary muscles
o Specialized miniature structure, where neurons influence
muscle contraction
 Components of NMJ
o Vesicles full of ACh
 Choline from GIT circulation  ECF  uptake
system concentrates choline into motor nerve endings
 Mitochondria provide Acetyl CoA
 Together with choline and the enzyme choline
acetyltransferase, this forms ACh
 Then transporters within vesicles take them up
What occurs when an action potential arrives?
 Once Na+ influx of action potential arrives, voltage-gated Ca2+
channels open
o This calcium influx  calcium mediated fusion of ACh
vesicles with the nerve ending membrane
 Calcium allows synaptobrevin (a type of v-SNARE)
on the vesicle and syntaxin and related proteins on
the nerve membrane
 Memory tip: Vesicles must taxi (syntaxin) then SNAP
(SNAP-25) to membrane. Vesicles have toetags
(synaptotagmin) since they will eventually die (and be carried
via retrograde transport/dynein.
o Essentially, exocytosis of ACh at synaptic cleft
o ACh then diffuses from high to low concentration toward post-
synaptic membrane (folding of sarcolemma)
 Crests of Post-synaptic membrane have higher concentrations of ACh
receptors (AChR)

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2 Types of AChR 15
 Ionotropic (ion channels)
o Nicotinic— ligand-gated
channel on post-synaptic
membrane
 In skeletal muscle
 muscle
contraction
 Metabotropic (GPCRs)
o Muscarinic
 In cardiac muscle
 decreased HR
Structure of the nicotinic AChR: The nicotinic AChR is a heteropentamer with the subunit composition of α2βγδ.
These subunits are homologous to one another, and each has four membrane-spanning segments (M1 to M4).
For α, β, γ, δ subunits, each has 4 hydrophobic regions (M1-M4) and each has M2 transmembrane segment
lining the aqueous pore through which Na+ and K+ cross the membrane

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 Stimulation of nicotinic AChRs at postsynaptic membrane  influx of Na+ 

local potential (membrane potential becomes less negative i.e. more positive)
called end-plate potential (an example of excitatory post-synaptic
potential)
 When this end-plate potential reaches threshold  stimulation of voltage-
gated Na+ channels
o Heavy influx of Na+ begins  wave of depolarization of muscle
 Wave of depolarization spreads over the muscle sarcolemma to
the T tubules  goes in and releases Ca2+ in the cytosol of the
muscle  Ca2+ mediated contraction of the muscle occurs, with
actin myosin sliding
 So, in this way, electrical energy is converted into mechanical
energy
Why/How Is acetylcholine degraded?
 Must be degraded or there will be a sustained contraction!
 Acetylcholinesterases destroy ACh (see figure at bottom of page)
Clinical
 All diseases which impair NMJ transmission are painless
 Types:
o Autoimmune (immune system produces antibodies directed against
NMJ components)
 Myasthenia gravis
 Lambert-Eaton Syndrome
o Congenital Myasthenic Syndromes
o Toxin-mediated/Rx Mediated
Myasthenia Gravis
 85% of patients have autoantibodies against nicotinic ACh receptors at NMJ
o Must specify since there are many AChR around the body
 15% of patients have autoantibodies against MuSK proteins  unable to
maintain healthy concentration of AChRs
o MuSK (muscle-specific kinase)— when stimulated, tyrosine proteins
are phosphorylated
 Full name is muscle specific tyrosine kinase receptor
 This protein is present in the sarcolemma (of course this is
postsynaptic), muscle specific receptor, and produces kinase
activity in tyrosine
 Important since it regulates the density of AChRs on
postsynaptic membrane
Lambert-Eaton
 Major difference is that although autoantibodies are formed, they are
directed against presynaptic voltage-gated Ca2+ channels
o  Impaired Ca2+ influx  impaired release of vesicles/ACh
Congenital Myasthenic Syndromes
 NOT autoimmune mediated (so immunosuppressive therapy will not work)
 These patients have inherited defective genes (coding for NMJ proteins)
o Supposed to make either pre-synaptic, synaptic, or post-synaptic
membrane proteins

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Clostridium Botulinum Toxin

 Gram positive anaerobic bacteria
o Found in home-cooked food, especially canned foods
 Ingested toxin  GIT  blood/circulation  ECF  taken up by cholinergic
nerve endings (NMJ nerve endings as well as autonomic nerve endings)
o Toxin is a protease, which cleaves synaptobrevin  vesicles can no
longer fuse or release ACh
o Very lethal toxin— 1microgram ingestion can kill a human
o Occurs very rapidly
 Must treat quickly
Curare Toxin
 Also called tubocurare
 Binds with nicotinic AChRs, and blocks them  impairment of NMJ
Aminoglycosides
 Gentamycin especially
 Impaired function of voltage-gated Ca2+ channels on presynaptic
membrane impaired release of vesicles/ACh
 Remember of course that this is only in some patients, or it would be
classified as a toxin not a drug
Other drugs causing NMJ dysfunction (Act presynaptically)
 Quinine
 Β-blockers
 Procainamide
 Tetracyclines
 Essentially, none of these drugs should be given to patients with myasthenia
gravis!
Myasthenia Gravis 2
 Myasthenia = weakness; gravis = serious

 85% of patients have autoantibodies against nicotinic ACh receptors at NMJ
o Must specify since there are many AChR around the body
 15% of patients have autoantibodies against MuSK proteins  unable to
maintain healthy concentration of AChRs
 Mortality has reduced from 30% to 5%
 Bimodal age distribution
o Younger patients: 20-30, more likely females with hyperplasia of
thymus
o Older patients: 40-60, more likely male with thymus cancer
 Autoantibodies
o Type II hypersensitivity
 Treatment
o Plasmapheresis (since autoantibodies found in blood plasma)
o Immunosuppressive therapy
 Edrophonium test inhibits acetylcholinesterase

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Detailed pathogenesis of AChR autoantibodies

 Autoantibodies are IgG (this means it can cross the placenta)
C9s of MAC require
o Divalent antibodies (can bind with 2 antigens)
C5b—C8 present
o  Pathological clustering of receptors
o MC antibody target is ACHR α subunit called Main immunogenic
region (MIR)
 These pathological clusters are then internalized and killed via endocytosis
and lysosome fusion  catavalent destruction
 What is the problem with this?
o The autoantibodies have pathologically accelerated
endocytosis/destruction of receptors (normal receptor turnover)
o Cell is unable to compensate
 Note— autoantibodies “blocking” ACh is the minor mechanism (major
mechanism is autoantibody/receptor cross-linking and clustering 
endocytosis/degradation)
 Fc portion of autoantibodies become active, and activate complement
proteins
o C1  C4  C2  C3 convertase activating C3  C3b  C5b  C6 
C7  C8  C9  MAC  membrane loses function
o This leads to morphological/structural alteration of the membrane!
 Less infolding/crests are removed
 i.e. degeneration of postjunctional folds
 So, 3 things happen to decrease NMJ transmission:
o Increased synaptic cleft gap
o Decreased membrane surface area
o Decreased AChR pre unit area*
MuSK autoantibodies
 These antibodies do NOT activate complement
 Do NOT have thymic abnormalities
 So of course, no thymectomy performed (it is treatment in the 85% of MG
patients with AChR autoantibodies with thymic abnormalities, however)
Role of thymic abnormalities in Myasthenia Gravis

Types of thymic abnormalities (MC in MG patients with AChR autoantibodies)
 10% have thymoma (most are benign, some can become malignant)
o More common in older men
o Are neither B or T cell tumors, but thymic epithelial cell tumors
(these cells normally nurse developing T cells)
 50% or more have thymic hyperplasia
o More in younger women
o This is a B cell tumor (B for Breast and of course breast for female)
 B cell follicles in the thymus (remember that thymus does not
only house T cells!)

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 Those females without thymic abnormalities are more likely to suffer from
other autoimmune diseases
 Ex: Hashimoto’s, Type I DM, etc.
Role of thymus in MG
 Myoid cells are stromal cells present inside the thymus
o On their surface express sarcolemmal proteins like AChR
o Normally these proteins are presented in the thymus, and there is
suppression of those T and B cells which can recognize these proteins,
so autoimmunity does not occur
 However, those with thymoma/thymic hyperplasia  disturbed thymic
function
o So when the antigens (AChR) are presented to B or T cells of the
thymus, they react to them and produce autoantibodies
Clinical
 Painless muscular weakness
o Of voluntary muscles (does NOT involve smooth muscles, cardiac
muscle)
o Insidious onset (unlike botulinum toxin)
 May not be diagnosed for years
o Fluctuating (sometimes more or less)
o Sustained/repetitive effort increases fatigue rapidly (unlike Lambert-
Eaton)
o Fatigue gets worse throughout the day
 Which muscles are involved?
o Initially they are cranial muscles, especially extraocular muscles
  Ptosis of upper eyelid
  Diplopia (extraocular muscle weakness means they cannot
move the eyeballs in a coordinated fashion)
o May also develop difficulty in mastication and swallowing
o Bulbar muscle problems (those cranial nerves coming from the bulb-
medulla = CN IX, X, XI, XII)
 Control articulation, phonation, swallowing
 Leads to:
 Dysarthria (articulation/speech becomes difficult and
slurred)
 Dysphonia (difficulty speaking due to physical disorder
of mouth, tongue, throat, or vocal cords)
o Phonation is production of sound from the
larynx, which is then converted by movement of
the tongue, lips, and soft palate
 Nasal twang due to dysfunction of soft palate
o Myasthenic snarl (cannot smile properly)
o Disease usually spreads downward
 Neck, limb girdles (shoulder, hip)

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 However, the real danger in involvement of respiratory

muscles
 Called myasthenic crisis, may require mechanical
ventilation
 Important to know direction of spread (opposite in Lambert
Eaton
 MG patients with anti-MuSK antibodies (15%) have more focal muscle
weakness
Diagnosis
 Patient history
 Physical exam (weakness in cranial regions)
o Sensations and deep tendon reflexes are NORMAL
 Autoantibodies (anti-cholinergic or anti-MuSK)
 Decreasing muscle response to repetitive stimulation of motor nerves
(decremental response)
o Vs. Lambert-Eaton, where repetitive stimulation  transient increase
in muscle response (incremental response)
 CT Scan/MRI to look for thymic abnormalities
 Tensilon test— administration of Edrophonium (short acting anti-AChE)
o This increases the concentration of ACh, and even though there are
less receptors than normal, this may be enough to improve weakness
and allow contraction of muscles
 Significant rapid/transient improvement
o Vs. Lambert-Eaton, does not improve
 Another test:
o Ice applied to upper eyelid for 2 minutes
o This freezes the AChE, leading to transient muscle improvement
Treatment
 First line is anticholinesterase drugs
o Once you have confirmed with short-acting Edrophonium that the
disease is present, you give longer-acting drugs
o Pyridostigmine
o Neostigmine
o Unfortunately, over the years they lose their efficacy, since AChR
concentration becomes so low that even additional ACh does not help
much
 Immunosuppresants
o Reduces production of autoantibodies
o Corticosteroids, and with them can give
 Azathioprine
 Cyclosporine
 Plasmapheresis
o Removes autoantibodies from blood plasma
o Can also give IV immunoglobulins
 Thymectomy in those with thymoma or thymic hyperplasia

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o Remember that these are mostly found in those with AChR

autoantibodies not anti-MuSK Note— small cell carcinoma of the lung which
autoantibodies occurs in LE is because autoantibodies against
o 50% show significant benefit, voltage gated Ca2+ channels in the lung cross
25% full remission, 25% no react with those in presynaptic NMJ
benefit
 Avoid drugs mentioned above that can worsen Myasthenia Gravis
Lambert Eaton vs. Myasthenia Gravis
 Commonly
o Painless muscle weakness (do NOT affect cardiac or smooth muscles)
 Both can affect respiratory muscles
o Impaired NMJ transmission
o Autoimmune with antibodies present in circulatory system
 Differences
o Autoantibodies: MG against AChR/MuSK which are postsynaptic vs. LE
against voltage-gated Ca2+ channels which are presynaptic
o Tumor associations: MG associated with thymoma (tumor of thymic
epithelial cells; normally benign can be malignant), LE associated
~50% with small cell carcinoma of the lung
 LE may appear 2-3 earlier than cancer appearance
 Must do serial 6 month imaging for this reason
 The other 50% not associated with small cell carcinoma of the
lung have other autoimmune conditions (vitiligo, Hashimoto’s,
Type I DM, etc.)
o Clinical presentation: MG has cranial muscles weakness (which
present as ptosis, diplopia, dysarthria, dysphagia, dysphonia), LE
starts with limb girdle muscle weakness (Lambert for Limb)
 Lambert Eaton patients develop gait problems first, then eye
problems
 Myasthenia gravis patients develop eye problems first, then
gait problems
o Clinical Presentation: MG weakness starts superiorly and moves
downward, LE starts in lower limbs and can move upwards
o Response to sustained effort: MG patients become quickly fatigued, LE
patients rapidly but transiently improve
 Since Ca2+ builds up presynaptically with repetitive Aps
 Memory tip: Lambert eaton can eat the lamb
 MG starts well but then looks at lamb with droopy eyes,
LE starts poorly but finishes the lamb with muscle
improvement
o Electrophysiological studies with repetitive nerve stimulation: MG
patients show decremental response, LE patients show
incremental response

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o Edrophonium test: MG shows improvement, LE doe NOT (NMJ

problems not due to ACh)
o Treatment: MG use AChE, immunosuppression, plasmapheresis,
thymectomy; LE use immunosuppression, treat small cell carcinoma
of the lung, plasmapheresis, 3,4-diaminopyridine
 3,4-diaminopyridine— blocks voltage-sensitive K+ channels
(preventing K+ efflux)  membrane depolarized for a longer
time  longer time for Ca2+ influx!
o Anticholinesterase treatment: MG works, LE does not
Note— Voltage-gated Ca2+ channels are present elsewhere in the body, such as
cerebellum ( ataxic gait) and autonomic nervous system ( dysautonomia);
applies to LE patients

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II. Overview of Nervous System + Introduction to Neuroanatomy
Basics
Nervous system is divided into CNS and PNS
CNS = brain and spinal cord
 Function:
o Collects sensory information about the self and the environment
 Compares information with past information (ex: recognizing
people)
 Then integrates information and decides on a motor response
(ex: smiles at person)
PNS
 Function:
o To take information to the CNS
o Also to take motor decisions from the CNS to the periphery
PNS
Motor PNS (CNS output)
 Somatic Motor Responses (Voluntary)
o Skeletal muscles
 Autonomic Motor Response (Involuntary)
o Divided into:
 Sympathetic
 Parasympathetic
o Smooth muscle, cardiac muscle, glands
o Normally, have a balance of parasympathetic and sympathetic
activity, but in certain situations one or the other will increase
Sensory PNS (CNS input)
 Special sensations
o Generated only from a certain part of the body (ex: cannot see with
anything other than eyes)
 Vision, taste, olfaction, hearing (cochlear system), equilibrium
and position (vestibular system)
 General sensations (can occur from any part of the body; ex: touch/temp)
o Somatic Sensations
 Sensations from the superficial areas of the body, such as skin
and the locomotor system (muscles, joints, etc.)
 Light touch, pain, temperature, proprioception (awareness of
where you are in space; ex: while walking you never lift both
legs at once on accident, since CNS knows position of legs)
o Visceral Sensations
 Dull pain
 Distention
Consciousness of Sensation
 In order for us to be conscious of sensations, they must reach the cerebral
cortex

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o If they do not, we will not be conscious of those sensations (for

example, we may have been taking in information about position
sense a few minutes ago, but were not conscious of it. But now, if you
are asked to focus on position, you will be able to.
Basics of Neuroanatomy
 Pons, medulla, and cerebellum make up the hind brain or
rhombencephalon
 In between the hindbrain and forebrain there is the midbrain or
mesencephalon
 Above that there is the forebrain or prosencephalon
o Outer part of the prosencephalon is called the telencephalon
o Deeper part of prosencephalon is called diencephalon
 Princess Diena (Diana) was the center of attention with
telescopes on all sides looking in
Remember Fetal derivatives too:
Cells of Nervous System

 Neuronal cells (Neurons)— true functional cells of CNS
o Collect info in the form of action potentials
o Have long processes called axons
o Gray matter— collections of neuronal cell bodies within the CNS
 The nucleic acids and other components in cell body nuclei
make it darker
o White matter— collections of axons within CNS
 Neuroglial cells— supporting cells
o Act as connective tissue for neurons

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Structural Divisions of Nervous System

 CNS
o Gray matter (collection of neuronal cell bodies)
 Cortex— gray matter exposed on surface of the brain
 Nucleus— Pieces of gray matter embedded within CNS and
surrounded by white matter (NOT to be confused with the
nucleus of a cell)
 Ex: if that collection of cell bodies (i.e. the nucleus) has
axons that go on to form CNVII, then it is the nucleus of
CNVII
 Basal nuclei— gray matter embedded deep within the
base of the cerebral hemisphere
o White Matter (group of axons)
 Can be classified by axis of fibers:
 Tracts— superior/inferior axis
o Ascending tracts— take information rostrally
o Descending tracts— take information caudally
 Commissural fibers— connect fibers R to L
o Corpus callosum— largest commissure
 Association fibers— Anterior-posterior
o Connect lobes together
o Reticular formation
 Network of gray matter and white matter in brain stem
 Since major sensory and motor white matter fibers
decussate in the brain stem, the gray matter and white
matter form a network
 When the gray matter breaks into fragments due to
white matter decussation, some fragments are large,
and are called reticular nuclei
o CNS contains Oligodendrocytes
 Around tracts of white matter
 PNS
o Nerves— collections of axons outside the CNS
 Motor Nerves— collection of axons taking info to body
 Sensory Nerves— collection of axons collecting info from
body
o PNS has Schwann Cells
 Around the axon of the nerves
Note: In spinal cord, gray matter is located on the inside, but in the brain, gray
matter is located superficially

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III. Cerebrospinal Fluid and the Ventricular System
CSF- clear, colorless, odorless fluid that is present within and around (sub-
arachnoid space) the CNS (total CSF ~130mL, with ~500mL produced daily)
Within the CNS, there are several cavities that contain CSF
 At the top of the midbrain there are thalami
 Lateral ventricles- fluid filled cavities within the cerebral hemispheres
 Lateral ventricles are connected by the third ventricle (another fluid filled
space)
o Majority of the third ventricle passes between the two thalami
 Lateral ventricles communicate to the third ventricle via the foramen of
Monro
 Note: the cerebral hemispheres originate from the telencephalon; structures
around the thalamus originate from the diencephalon
o So we can say that lateral ventricles are structures of the
telencephalon, and the third ventricle is a cavity of the diencephalon
 As lateral ventricles are the cavity of the telencephalon, and the third
ventricle is a cavity of the diencephalon, cerebral aqueduct is the cavity of
the mesencephalon (present in the midbrain)
 Central canal contains CSF from spinal cord to mid-medulla
o At that point it expands outward and meets with cerebral aqueduct
(which also expands outward) to form the 4th ventricle
o Cavity of the spinal cord
 Fourth ventricle- located on the posterior aspect of pons and upper
medulla; anterior to cerebellum
o It is the cavity of rhombencephalon (hindbrain)
 Note: all ventricles/central canal are covered with ependymal cells
Formation of CSF
 Formed in the lateral, third, and fourth ventricles in a specialized structure
called the choroid plexus
o Located in the roof of the third and fourth ventricle, and
inferomedially in the lateral ventricles
 Choroid plexus structure:
o Choroidal arteries go through CNS into the cavity
 Inside they make specialized capillary lobes
 Choroidal veins go out
o This arterovenous bundle is covered by pia mater (i.e. takes a fold of
pia mater along with it)
 This is called tela choroidea
o When the tela choroidea reaches inside the cavity, it is covered by
cuboidal epithelial cells
 At that point the structure is called choroid plexus
Note (outside source): The CP consists of a layer of cuboidal epithelial cells
surrounding a core of capillaries and loose connective tissue. The CP epithelial layer
is continuous with the ependymal cell layer that lines the ventricles, but unlike the

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ependyma, the epithelial layer has tight gap junctions between the cells on the side
facing the ventricle (apical surface). These gap junctions prevent the majority of
substances from crossing the cell layer into the CSF; thus the CP acts as a blood–CSF
barrier.
How does the choroid plexus functionally produce CSF?
 Ependymal cells covering the tela choroidea actively secrete Na+
o There are active Na+ transporters present in the epithelium of the
choroid plexus
o Actively transport Na+ from cells to ventricular CSF area
 Na+ then attracts Cl-, which follows (passively)
 This means osmotic pressure in the ventricular CSF area increases
 The osmotic pressure pulls in water
 Now, these epithelial cells have transporters which transport glucose from
the blood
o But they are not very efficient, as opposed to Na+ and Cl- transport
o For that reason, the concentration of CSF glucose is < blood glucose
o The concentration is 2/3— ex: 100mg/dL in blood, 66mg/dL in CSF
 Few components are transported in the reverse direction (CSF  blood)
o K+ is one of them, so naturally CSF K+ is < blood K+ level
Tracing CSF flow
 Lateral ventricles make CSF in choroid plexus  third ventricle (via foramen
of Monro); some CSF is added from choroid plexus in 3rd ventricle  Fourth
ventricle (via cerebral aqueduct); some CSF is added from choroid plexus of
4th ventricle  Central canal
o Sometimes the end of the central canal is slightly dilated
o If so, it called the terminal ventricle (but it is a dead end),
surrounded by lumbar cistern
Now that CSF has been produced, it needs to leave the brain
 Pia mater covers brain, and arachnoid mater covers pia (PAD around brain)
 In between the pia mater and arachnoid mater is the subarachnoid space
 The 4th ventricle expands laterally as it moves inferiorly from the cerebral
aqueduct and superiorly from the central canal
o At these Lateral points of expansion are two
foramina called foramen of Luschka
o So the CNS moves laterally and exits from the
cavities within the CNS out to the subarachnoid
space via the foramina of Luschka
 At the point where the foramina of Luschka empty, the
subarachnoid space is slightly dilated (due to fluid)
and is called the pontine cistern (cerebellopontine
cistern)
 There is another foramen on the posterior aspect of
the fourth ventricle; it is a Median foramen called the
foramen on Magendie

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Scheme of roof of fourth ventricle. The arrow is in the foramen of Majendie.

1= Inferior medullary velum 2= Choroid plexus 3= Cerebellomedullary
cistern of subarachnoid cavity 4=Central canal 5= Corpora quadrigemina 28
6=Cerebral peduncle 7= superior medullary velum 8= Ependymal lining of
ventricle 9= Pontine cistern of subarachnoid cavity
o This foramen also releases CSF into the

subarachnoid space, into another cistern called the
cisterna magna (cerebellomedullary cistern)
 The important point is that the foramen of Luschka and
Magendie allow movement of CSF from within CNS to outside of CNS
(subarachnoid space)
Structure of the lateral ventricle
 Frontal horn- located in frontal lobe
 Posterior horn- located in occipital lobe
 Body of lateral ventricle- located in parietal lobe
 Inferior horn- located in temporal lobe
While the spinal cord terminates at L2, the subarachnoid space continues to S2
 In between those, a lumbar puncture can be obtained (usually between
L4-L5); more on this later
Tentorium cerebelli- dural fold between occipital lobes and cerebellum
Dura mater- outside arachnoid mater
 Has two layers
o Outer- periosteal layer
o Inner- meningeal layer
 Superiorly, these two layers separate, creating a triangular space
 This is part of a special venous drainage system
o Called the dural venous sinuses
o It is lined by endothelium (it is like a vein)
 This particular sinus is called the superior sagittal
sinus
o Involved in draining venous blood
o In this region, the meningeal layer of dura mater
has holes, connecting it to the subarachnoid
space
o Arachnoid mater goes through these spaces,
creating finger-like processes
 These are called arachnoid villi
 Together, they form an arachnoid
granulation
 Through these points, CSF is being drained from
subarachnoid space into dural venous sinuses
 Important point: arachnoid villi have many endothelial cells
o These cells contain vesicular channels
 Through these channels, CSF very easily moves to dural
venous sinuses
 They may even allows larger molecules to get through,
such as protein, and even RBCs sometimes
 Too many large particles may block
CSF flow
Note: arachnoid granulations only allows one way flow; if pressure
becomes too high, the channels will collapse and close, not allowing
backwards flow
Note: CSF pressure dependsDownloaded
mostly on drainage, NOT production
by Ayesha Khalid (ayeshakhalid_308@yahoo.com)
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Cerebrospinal Fluid and the Ventricular System 2 and 3
HY points missed from last video

 CSF is mainly produced in the lateral ventricle, with more CSF added from
other ventricles as fluid moves
 With age, arachnoid granulations increase in number and can even calcify
Functions of CSF
1. Acts as a cushion around the CNS (which floats in CSF present in
subarachnoid space)
o Advantage is if we sustain injury it protects the CNS
 However, let us say you suffer a severe injury to the back of the head— which
lobe is more likely to be injured, occipital or frontal?
o Frontal— skull moves suddenly forward and brain does not keep up;
negative space vacuum formed
o Called a contrecoup injury
Note (outside source): A coup injury occurs under the site of impact with an object,
and a contrecoup injury occurs on the side opposite the area that was hit. Coup
injury may be caused when, during an impact, the skull is temporarily bent inward
and impacts the brain. When the skull bends inward, it may set the brain into
motion, causing it to collide with the opposite side of the skull; this will result in a
contrecoup injury

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More functions of CSF

2. CSF and brain/CNS have similar specific gravity  brain floats in CSF
o Weight of CNS is 1400g, but when floating in CSF is only 50g!
 This is due to buoyancy (ex: moving boat in water easier)
o If this was not the case, very little movements would injure the brain
 How is it kept suspended?
o By the fine arteries, veins, and nerves that enter/exit it
o Along with arachnoid trabeculae
 Note (outside source): The arachnoid trabeculae are delicate
strands of connective tissue that loosely connect the two
innermost layers of the meninges – the arachnoid mater and
the pia mater. They are found within the subarachnoid space
where cerebrospinal fluid is also found
o Without CSF, the brain cannot be kept suspended by such fine
structures
 The proof of this is that if you remove too much CSF via lumbar
puncture, you can cause severe pain such as headache
 This is because nerves are pulled
 Pain can be relieved by injecting sterile saline
intrathecally (through dura mater into subarachnoid
space)
3. Acts as a reservoir and controls intracranial content
o For example, in old age as the brain shrinks, CSF will increase
 Remember that the skull is a fixed cavity
o Or, if there is a slight cranial swelling, CSF can decrease
 Of course if there is large swelling it will raise intracranial
pressure, however
4. Nourishes the CNS
o Note that CSF fluid has the same composition as the interstitial fluid of
the nervous system (no barrier between them)
 BBB (tight junctions of endothelial cells) does not simply let
everything into interstitial space— neurons require specific
environment
 Highly polar and large molecules cannot cross easily
 However, CSF fluid can freely move and exchange
with interstitial fluid of the brain
o Due to this, nutrients of CSF can easily go to extracellular fluid of the
brain, and nourish the neurons
5. Acts as a vehicle to remove waste products
o Glial cells and neurons have waste products which diffuse into the
interstitial fluid, some of which go into CSF
o Essentially acts as a metabolic waste removal system
6. Carries hormones within the CNS
o In the posterior aspect of the third ventricle is the pineal gland

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 Releases products into CSF, and from there they may keep
moving through CSF and reach the hypothalamus to regulate
the release of hormones
o Hypothalamus is anterior to the third ventricle
Features of CSF
 Volume of CSF ~130mL
 Daily production of CSF ~500-600mL
 Every minute ~0.5mL secreted
 Pressure (measured during LP) ~60-160 mmH2O, 7–
15 mmHg
o Higher if patient sitting up (200-300 mmH2O)
How is a lumbar puncture done?
 Patient lies in left lateral recumbent position
 The supracristal line (joins the iliac crests) is at L4
 Palpate the interspinous area
o Then either puncture above or below L4
 Point the needle toward the umbilicus of the patients
as you guide it through
 Which structures are pierced?
1. Skin/subcutaneous fascia
2. Ligaments (P to A order)— supraspinous,
interspinous, ligamentum flavum
3. Epidural space (only potential space in cranial cavity,
but in the vertebral column it is a real space)
4. Dura mater
5. Subdural space (very small)
6. Arachnoid mater
7. Subarachnoid space, which contains CSF
8. Do NOT pierce pia mater!
Note: usually take 5-10mL per bottle, and take 3 bottles
5 points on how to tell if there is risk of brain herniation:
1. Unexplained headache
2. Papilledema
o Normally the margins of the optic disc are sharp/clear
o If there is papilledema, then the margins are blurred
3. Projectile vomiting
o Vagus nerve is disturbed (and remember that it controls GI
motility)
 If it fires too much  projectile vomiting
4. Progressively increasing blood pressure (every day increases)
o Blood cannot easily reach CNS  ischemia  intense sympathetic
overflow, which constricts many blood vessels in the body to try to
push blood to the ischemic brain  increasing BP
5. Progressively falling pulse rate

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o Vagus is irritated, and overrides aforementioned sympathetic

stimulation of heart (which occurs as mentioned above due to
ischemic brain)
Why does papilledema  raised intracranial pressure?
 Dura mater makes a sleeve around the optic nerve
 This means that CSF also surrounds the optic nerve!
 Remember that the optic nerve is really a CNS tract not a nerve, so it is even
covered with pia and arachnoid mater
 Retinal artery (branch of ophthalmic artery, which is 1st branch of internal
carotid artery) passes through the dura, arachnoid, CSF to supply the retina
o The vein also passes through all those areas
o The retinal vein is compressed by high CSF pressure, so it has trouble
taking blood back (although retinal artery is okay since it is also a high
pressure system)
o CSF fluid also goes through and contributes to papilledema
Note (outside source): left lateral recumbent position stretches ligament flava and
increases distance between spinous processes and vertebral laminae
 1st pop: ligamentum flavum
 2nd pop: dura mater and arachnoid mater
 Once stylet is removed, CSF drips at rate of 1 drop/sec
 CSF only releases as a stream if subarachnoid pressure is high
 CT scan or exam of fundus via ophthalmoscope confirms
normal intracranial pressure (i.e. no danger of cerebellar
herniation, which could occur if increased intracranial
pressure)

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 For pain, give a local anesthetic for the skin prior to the procedure
CSF Disturbances in Meningeal Infections
Meningitis = inflammation of the leptomeninges
 pia mater and arachnoid mater together are called the leptomeninges
Normal CSF
 Color: clear
 Cells: very few lymphocytes, <5 lymphocytes/mL (cells of extracellular fluid
and connective tissue); NO neutrophils, NO RBCs
 Glucose: 2/3 of plasma level (which means it is smart to take blood and
measure blood glucose concurrently)
 Proteins: very low since not freely allowed to move into CSF, so ~0.4g/L
(plasma protein is 60-80g/L in contrast)
Pyogenic (pus-forming) bacterial meningitis
 Color: yellow, turbid
 Neutrophils: Very high (pus always has a lot of neutrophils)
 Lymphocytes: Low (low in acute inflammation, take a long time to
accumulate at the site of infection)
o Pyogenic bacteria produce chemotactic agents that attract the
neutrophil >lymphocytes
 Glucose: Low (<50% of plasma or blood glucose level)
 Protein: moderate-high (usually >1g/L): inflammation  increased capillary
permeability  increased protein
Tuberculous meningitis
 Color: turbid + fibrin web (fibrin leaks into CSF  web-formation)
 Neutrophils: Low (TB is chronic inflammation, whereas neutrophils are the
cells of acute inflammation)
 Lymphocytes: High (accumulate in chronic
inflammation)
 Glucose: Low (<50% of plasma or blood glucose level)
 Protein: very high (usually >1g/L): inflammation 
increased capillary permeability  increased protein
Viral meningitis
 Color: clear
 Neutrophils: Low
 Lymphocytes: High
 Glucose: normal (>50% of plasma or blood glucose)
 Protein: Mildly increased (usually <1g/L): inflammation
 increased capillary permeability  increased protein
o However, viral meningitis disturbs the microcirculation very little
Other CSF Findings
 Subarachnoid hemorrhage
o CSF vial has many RBCs, and after sitting for some time, at the top of
the vial there is a yellow substance called xanthochromia (from
degradation of RBCs)

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Meningitis Signs:
Kernig = Knee
CSF and Ventricular System 4 and 5
HY points missed in last lecture:

CSF pressure is mainly controlled by arachnoid villi acting as valves (not dependent
on production, which is mostly constant)
 Peduncle
o Very big bundle of white matter connecting the brainstem to the
cerebrum

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o Very big bundles of white matter connecting the brainstem to the

cerebellum
 Cerebral peduncles (green) peduncles connect the brainstem to the
cerebrum
 Cerebellar peduncles (blue):
o Connecting the midbrain to the cerebellum
o Connecting pons to cerebellum
o Connecting medulla to cerebellum
 Interpeduncular cistern (red) – CSF-filled space in between the two
cerebral peduncles
o Unlike the other cisterns we have discussed, no foramina open
into this cistern
Recall that CSF gets absorbed in the superior sagittal sinus
What can lead to the increased CSF seen in hydrocephalus?

Hydrocephalus- excessive CSF within the cranial cavity (skull)
1. Increased CSF production
a. Normally, CSF production is very stable
b. Major causes of CSF pressure changes are not due to production
problems, but rarely you may encounter a patient with this issue
c. Recall that CSF is produced by the choroid plexus
i. Tumor of choroid plexus  excessive production of CSF
2. Abnormal circulation of CSF
a. Foramen of Monro blocked by a cyst, called choroid plexus cyst of
the third ventricle  intermittent hydrocephalus (cyst sometimes
blocks, sometimes does not)
i. This leads to expansion of the lateral ventricle  asymmetrical
enlargement  damage of the brain (seen on right)
b. Cerebral aqueduct blocked
i. Can have congenital cerebral aqueduct stenosis  bilateral
symmetrical enlargement of lateral and 3rd ventricles 
macrocephaly (sutures have not fused yet)
ii. Tumor
c. Cerebellar tumor— may block foramen of Magendie, and if it expands
laterally, may also block the foramen of Luschka
3. Reduced CSF Drainage
a. Tuberculous meningitis— produces so much caseous material at the
base of the brain, that if tuberculous meningitis patients survive, there
will be severe fibrosis (scarring) at the base of
the brain
i.  CSF cannot circulate well in the
subarachnoid space
b. Arachnoid villi/granulations can be
clogged/blocked
i. Hemorrhage  RBCs clog it

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ii. Infections  WBCs or bacteria clog it

iii. Congenital arachnoid gran. problems
1. Low number
2. Low efficiency
c. Thrombosis in superior sagittal sinus
d. Internal jugular vein blockage (rare cause) via tumors at base of brain
i. CSF pressure increases everywhere behind it
Drainage of Sinuses
 Note (outside source): The crista galli (Latin: "crest of the rooster") is a
median ridge of bone that projects from the cribriform plate of
the ethmoid bone. It is where the falx cerebri attaches
anteriorly to the skull
 Drainage flow: Superior sagittal sinus (along falx cerebri) 
transverse sinuses (along tentorium cerebelli)  sigmoid
sinuses  jugular foramina  internal jugular vein
Types of Hydrocephalus
 Non-communicating hydrocephalus
o When foramen of Monro, cerebral aqueduct, or
Foramen of Magendie/Luschka are blocked, it means CSF from the
ventricular system cannot communicate with the subarachnoid space
 Communicating hydrocephalus
o This when the CSF from the ventricular system can communicate with
the subarachnoid space
o Causes include all those listed under “Reduced CSF Drainage”
Treatment
 Ventriculo-atrial shunt— silicone tube from ventricular system to right
atrium
 Ventriculo-peritoneal shunt— silicone tube from ventricular system to
peritoneal cavity
Unusual types of Hydrocephalus
Normal Pressure Hydrocephalus (type of communicating hydrocephalus)
 3 Ws: Patient becomes Wacky, Wobbly, Wet
o Wacky = dementia
o Wobbly = gait abnormalities
o Wet = urinary incontinence
 Drainage at arachnoid villi is impaired
 Usually the cause is:
o Prior head trauma, when patient developed meningeal hemorrhage
o Some RBCs stick to villi  healing via fibrosis  arachnoid villi
cannot drain well
 Rather than pressure increasing, the brain shrinks to accommodate
o If a lot of the cerebral cortex atrophies  dementia
o The area affected is the supero-medial portion of the cortex
(circled in drawing on right), which controls urination and gait 
gait abnormalities and urinary incontinence

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Hydrocephalus Ex Vacuo
 Not true hydrocephalus—ICP is normal, solely due to neuronal degeneration
 In these patients, the caudate nucleus undergoes degeneration and atrophy
o So, lateral ventricles enlarge
 This is because the lateral ventricles and caudate nuclei are
very close (as seen in drawing on the right)
 Note— in Huntington’s chorea, the caudate nucleus atrophies and
shrinks; naturally the lateral ventricles appear enlarged
Pseudo Tumor Cerebri
 Young, obese females with clinical features suggestive of a tumor;
however, no tumor found on MRI/CT
o Symptoms:
 High CSF pressure
 Papilledema
 However, ventricles appear slit-like, as if they are being compressed!
 Problem is with drainage of CSF, but exact pathology unclear
Step 2/3 CSF Info
 Compression of internal jugular vein should increase CSF pressure on person
in left lateral recumbent position
 If pressure does not increase when pressing on internal jugular vein (which
is after superior sagittal sinus drainage) then the blockage is in the spinal
cord region (remember that it is also surrounded by CSF)
 Queckenstedt’s sign— this sign is positive when the subarachnoid space of
the vertebral column is blocked
o Positive: left lateral recumbent position; blockage of internal jugular
vein does not elevate CSF pressure
Blood Brain Barrier
 Barrier between the blood and the extracellular fluid (interstitial fluid) of the
brain
o Composed of very specialized capillary endothelial cells and tight
junctions (composed of special proteins— occludins and claudins)
o Note- it was initially thought that there were 2 additional anatomical
components to the BBB: basement membrane and astrocyte (glial
cells of CNS) foot processes
 Circumventricular organs— physiologic fenestration of epithelium (sense
components of blood, so they must take up portions of blood, like sampling)
o Hypothalamus (senses hormone levels within blood)
o Area postrema (can sense toxins  nausea/vomiting)
o Pineal gland
 Note— in CNS tumors with rapid angiogenesis, the BBB is not established
(since they do not have astrocytes to induce tightening of tight junction)
 Inflammation/infection produces inflammatory mediators  shrinkage of
endothelial cells  broken BBB
o Many antibiotics do not cross the BBB

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o However if bacteria are really there, then BBB will be broken and
antibiotics can get them!
Blood CSF Barrier
 Capillary endothelium, surrounded by basement membrane, glial cells, and
then very specialized choroidal cells with long cilia (assist in the circulation
of CSF)
 Choroidal capillaries are fenestrated! (meaning the barrier is not at the
endothelium level)
o Instead, the barrier is due to the strong tight junctions between
choroidal epithelial cells
 Note— BBB is due to endothelial cells, blood-CSF barrier is due to the tight
junctions of choroidal epithelial cells
Newborns
 BBB is quite permeable
 This is why if newborns develop jaundice, some bilirubin can reach the CNS
and cause damage, a condition called kernicterus
o Destroys the basal ganglia  motor problems
o Can cause mental retardation
Note: There is not ECF-CSF barrier! This means that anything you put in the CSF
goes to the brain
 This means that the pia mater and ependymal are not effective barriers
Blood Brain Barrier (These notes only notes include missing

info from earlier)
Types of capillaries:
Continuous
 No gaps, have basement membrane

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Fenestrated
 Contain endothelial windows allowing transcellular transport (aka
fenestrated capillaries)
Sinusoidal
 Many gaps, but also have macrophages in reticuloendothelial system, etc.
BBB and Transport Across it
 Paracellular transport (used to carry large, polar molecules) is blocked by
tight junctions (made of occludins and claudins)
 Transcytotic vesicular transport occurs but to a very limited degree
 So, the reason for the strong barrier in the BBB is not only due to tight
junctions blocking paracellular transport, but also from:
o Endothelial cells (of capillaries) engaging in very little transcytotic
vesicular transport (whereas other capillaries do)
o Lack of endothelial windows (present in other capillaries as well)
What if some “nasty substances” get in?
 Ex: lipid soluble neurotoxin gets past BBB
o p-glycoproteins (present on luminal side of the endothelial cells) will
throw out those substances (lipid-soluble: neurotoxins, drugs, etc)
 Note these are multi-drug, nonspecific, and are ATP-driven
active transporters
o This is good but can be bad if we want to administer certain drugs (we
are trying to find a way to block these)
Components of BBB
 Basement membrane comes next
o Note- in between astrocyte foot processes and basal lamina are
pericytes (microglial cells; control vessel tone; ensure low levels
transcytosis, thereby prevents toxins from crossing BBB)
 Astrocyte foot processes are up against the basement membrane
o Recall that these do not provide a real barrier
o The purpose of these foot processes is that they release
soluble substances which force the endothelial cells to
produce and synthesize occludins/claudins to tighten the
tight junctions
 Note- capillaries of the endoneurium of the peripheral nerves
also have endothelial cells with tight junctions and without
fenestrations and without effective transcytotic transport
What canNOT pass through BBB?
 Large molecules such as plasma proteins cannot cross
o This also means that all substances bound to plasma
proteins cannot cross!
 Ex: protein-bound drugs
 Highly charged molecules— become less lipid soluble so cannot
cross
o Protons cannot cross (highly charged)
 Toxins (even if small, uncharged, and lipid-soluble)

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What CAN pass through BBB?

 Little molecules
o Oxygen
o Carbon dioxide
o H2O
 Glucose (even though it is large and polar)
o Has a facilitated transporter— GLUT1 (insulin independent)
o Write one as a roman numeral— “I” for Independent
 Not just glucose, but all essential larger molecules have facilitated transport
o Amino acid transporters
 Ex: L-DOPA can cross whereas DOPA cannot (too polar)
 Once inside, L-DOPA is converted to DOPA
o Free form of thyroid hormone, steroid hormones
 NOT protein bound form, remember
o Nucleosides, choline
Blood-CSF Barrier
 Fenestrated endothelial cells of capillaries, in contrast to BBB
 No tight junctions
 This means that transcellular and paracellular transport are possible?
o Not so fast… when they get deeper, they reach specialized ependymal
cells form the barrier (does not allow substances from the blood to
reach CSF)
o Also called choroid epithelial cells
 Confused about the order? It goes: endothelial cells, endothelial cell
basement membrane, ependymal cell basement membrane, choroidal
epithelial cell (ependymal cell)
In what circumstances are the BBB Broken?
Circumventricular organs are physiologically present (“windows” that allow
special exchanges)
Pathologically
 Causes:
o Trauma
o Inflammation
o Infection
o Irradiation
o Neoplasm
o Hypertensive encephalopathy
 This leads to substances getting through inappropriately, and water follows
 swelling of the brain
o Called vasogenic edema— when due to some pathologic process, the
BBB is disrupted
More on circumventricular organs

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Named circumventricular organs since they all surround the third and fourth
ventricle. They are:
1. Posterior pituitary (neurohypophysis)
2. Median eminence (part of hypothalamus)
 Anterior wall of 3rd ventricle
3. Organo vasculosum of lamina terminalis (located anteriorly
to the lamina terminalis) also called OVLT
 Embryological significance of the lamina terminalis: it is the
point of closure of the anterior neuropore
 If the anterior neuropore does not close (at ~25 days)
then the lamina terminalis does not form
  anencephaly
 In between the interventricular foramina just superior to the roof of the 3rd
ventricle are structures passing above it called fornix (white matter fibers
arching anteriorly from hippocampal gyrus)
4. There lies the subfornical organ
5. Pineal gland is located on the posterior aspect of the 3rd ventricle
o Note— pineal gland and anterior pituitary are not considered part of
the brain, just associated with the brain
o An endocrine gland producing hormones, most notably, melatonin
 Controls sleep/wake cycle and circadian rhythm
 Also controls onset of puberty
 At a young age, melatonin is produced in higher
amounts, and keeps the gonadal functions suppressed
o Although it is not even considered part of the brain, it may be
considered a circumventricular organ, where BBB is broken
6. Subcommissural area— located under the posterior commissure which
connects pretectal nuclei of midbrain

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o Tracts— bundle of fibers which connect the superior-inferior axis of

the brain are tracts
o Association fibers— bundle of fibers which connect the
anterior/posterior axis of the brain are tracts
o Commissures— bundle of fibers which connect the right-left axis of
the brain are tracts
7. Area postrema, 2 structures bilaterally located at the floor of the 4th
ventricle in its most ventral part
Functions of circumventricular organs
 Sensory:
o Subfornical— thirst
o OVLT— osmotic substances
o Area postrema— emetic substances
 Secretory:
o Posterior pituitary— hormones
o Median eminence
o Pineal gland— melatonin

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IV. Blood supply to CNS

Cardiac Output to Brain
 Heart normally pumps ~5L
blood/min (this is the cardiac
output, in a resting person)
 ~15% of cardiac output is
devoted to CNS
Major sources of blood supply to the
brain
 Internal carotid artery (off
common carotids)
 Vertebral arteries (off
subclavian arteries)
o Posterior to the carotid
system
o Begin lateral to carotids
then becomes medial as they ascend
 The internal carotid and its branches are
also called the anterior system
 The vertebral/basilar system is also called
the posterior system
Vertebral system
 In the transverse processes of the
cervical vertebrae there are foramina
 Through these transverse processes, the
vertebral arteries pass through
 Then, through the foramen magnum, they
enter the cranial cavity (image)
 Note: as major arteries enter into the
cranial cavity, they are present in the
subarachnoid space! This means they
must pierce the dura mater
o In this space, berry aneurysms form
(clinical tie in)
 Both vertebral arteries join at the
pontomedullary
junction and
continue as the
basilar artery
Note: MCC of
neurologic dysfunction are vascular events, so you
must understand cerebral blood supply!

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Note- Branches of Int. Carotid are OPAAM: Ophthalmic, Posterior communicating, Anterior choroidal,
Anterior cerebral artery (ACA), Middle cerebral artery

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Vertebral/Basilar System + Branches

Anterior spinal artery comes off both vertebral arteries, inferior to their joining
(descends down anterior median fissure of the spinal cord)
 Anterior 2/3 of spinal cord supplied by sulcal artery of anterior spinal
artery (above)
 Segmental medullary arteries arise at multiple levels to reinforce the blood
flow to anterior portion of the spinal cord (anterior spinal artery alone does
not have enough blood to traverse entire cord)
o They enter laterally, and as they move medially, they divide into
anterior (anterior radicular artery) and posterior (posterior
radicular artery) divisions
o The great anterior segmental medullary artery (of Adamkiewicz)
occurs on the left side in most people, and also reinforces circulation
to anterior 2/3 of spinal cord
 Usually arises from posterior intercostal artery
Posterior Spinal Arteries
 Note- only one anterior spinal artery, but two posterior spinal arteries
 Origin is usually off PICA (anatomical variation— can be off vertebral artery)
Which arteries actually supply segmental arteries?
 Neck: deep cervical artery
 Thorax: Intercostal Artery
 Lumbar region: Lumbar artery
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Clinical
 There are a few areas which are already weak from receiving less blood
supply (physiologically), so infarction proximal to it means it will always be
affected first
o In anterior spinal artery territory these areas are at the level of T4, L1
o In posterior spinal artery territory these areas are at the level of T1-3
Posterior Inferior Cerebellar Artery (PICA)— off vertebral arteries
 Supplies the undersurface of the cerebellum
 Note— also supplies the lateral medulla
 Side note: pica— an urge to eat non-nutritious foods (occurs in pregnant
women), ex: clay, dirt, etc.
Anterior Inferior Cerebellar Artery (AICA)— off basilar (75%) or vertebral
 Also supplies the undersurface of the cerebellum
 Note— also supplies lateral pons
Labyrinthine artery— off AICA (85%) or basilar
 Goes through internal acoustic meatus to supply inner
ear/labyrinthine system; travels with CNVII and
CNVIII

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Superior Cerebellar Artery— supplies rostral pons and superior surface of

cerebellum
 Do not confuse this with cerebral arteries
 Runs inferior to Oculomotor nerve (CNIII)
Posterior Cerebral Artery (PCA) comes off basilar artery just superior to
occulomotor nerve (CNIII)
 Supplies: posterior part of the cerebral hemisphere, midbrain
 Runs superior to Oculomotor nerve (CNIII)
 Occlusion  contralateral hemianopia with macular sparing
__________________________________________________________________________________
Blood Supply to Brain 2
Carotid System
 The internal carotid artery arises from common carotid from aortic arch
 Passes through carotid canal which superiorly to the foramen lacerum
o Note- the internal carotid artery does NOT enter the foramen lacerum
 It has now entered the middle cranial fossa and passes through the
cavernous sinus
 It then turns sharply and moves medial to the anterior clinoid process, and
pierces both the dura mater and the arachnoid mater and enters the
subarachnoid space
Branches of Carotid Artery
Central Retinal Artery
 Branch of the ophthalmic artery, which enters into the optic cavity via the
optic canal
 Clinical importance: thrombi from L heart (mitral/arotic valve, L atrium) or
atherosclerotic plaque (common in carotid sinus) may travel to the central
retinal artery  blindness
o One of the features of anterior circulation (internal carotid
circulation) failure is blindness in one eye due to occlusion of central
retinal artery
Posterior communicating artery (PComm)
 Branch of the internal carotid artery that acts as a communication between
the carotid (anterior) and vertebral/basilar system (posterior)
 Specifically, connects posterior cerebral artery to internal carotid artery
Anterior choroidal artery
 Comes off of the internal
carotid artery (anterior
circulation)
Posterior choroidal artery
 Comes off of the posterior
cerebral artery

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Middle Cerebral Artery (MCA) and Anterior Cerebral Artery (ACA)

 Terminal branches of the internal carotid artery
 The anterior cerebral artery moves anteriorly, while the middle cerebral
artery moves laterally
Circle of Willis
 Advantage is that it is a unique type of cerebral supply system
o Communicating arteries— usually blood meets in the middle, but if
there is a block, the other side will help perfuse that area

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What areas of the brain do the cerebral arteries supply?

 Anterior cerebral artery: moves upwards then arches backwards over corpus
callosum (pericallosal artery below)
 On the medial side of the parietal lobe inside the median longitudinal
fissure you find the anterior cerebral artery
o Gives off cortical branches to the medial surface of the frontal and
parietal lobes, as well as the upper part of the frontal and parietal
lobes (branches are long enough for that)
 When the internal carotid bifurcates into its terminal branches (middle
cerebral artery and anterior cerebral artery), the middle cerebral artery then
reaches the stem of the lateral sulcus
o This position at the most medial aspect of the lateral sulcus (or stem)
can only be seen when the temporal lobe is reflected back (below)
o The middle cerebral artery then divides into its terminal branches at
this point, and continues until it reaches the lateral edge of the lateral
sulcus
o Lenticulostriate (Anterolateral central) arteries ranches of M1
supply the basal ganglia and internal capsule
 Infarction may  damage to internal capsule  contralateral
hemiparesis and sensory deficit

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 Clinical Significance:
o Looking at the homunculus, the foot/leg area is supplied by the
anterior cerebral artery (more medial), but arm/trunk/head/neck is
supplied by the middle cerebral artery (more lateral)
 There will be contralateral paralysis based on occlusion site
 Contralateral due to pyramidal crossing
However, if deep cortical branches of M1 (lenticulostriate branches) are occluded, the internal capsule,
which takes fibers from corona radiata, will be infarcted  complete contralateral hemiplegia (including
legs) even though only MCA is involved. NOTE: internal capsule infarct is a classic lacunar infarct and is
pure motor, i.e. presence ofDownloaded
other symptoms makes it less likely, and cortical infarct more likely
by Ayesha Khalid (ayeshakhalid_308@yahoo.com)
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The Posterior Cerebral Artery (PCA)

supplies: the midbrain (main
supply), inferior temporal lobe, and
occipital lobe (pictures below)

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Anterior clinoid process
Posterior clinoid process

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V. Meninges and Types of Intracranial Hemorrhage 55
Pia mater
-Recap: Very delicate, highly vascular, closely covers surface of CNS
-In the spinal cord, pia mater forms the denticulate ligaments
 Makes flattened projections outwards (from spinal cord) which connect the
pia mater (through subarachnoid space and arachnoid mater) to the dura
mater
 They anchor the spinal cord with the dura mater
 On each side, there are 21 denticulate ligaments
Arachnoid Mater
 Recap: Nonvascular, outside pia mater, subarachnoid space is full of CSF
 The subarachnoid space extends downward to S2
o The spinal cord ends at L2 in what is called the conus medullaris
 The pia mater extends up to the conus medullaris, and stops
 Except for a single string of pia mater called filum
terminale internum internum which extends to S2
 However, the arachnoid and dura continue to S2
 Note (Moore Clinical anatomy p. 498):
o The filum terminale is the vestigial remnant of the caudal part of the
spinal cord that was in the tail-like caudal eminence of the embryo. Its
proximal end (the filum terminale internum, or pial part of the

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terminal filum) consists of vestiges of neural tissue, connective tissue,

and neuroglial tissue covered by pia mater
o The filum terminale perforates the inferior end of the dural sac,
gaining a layer of dura and continuing through the sacral hiatus as the
filum terminale externum (or dural part of the terminal filum, also
known as the coccygeal ligament) to attach to
the dorsum of the coccyx
o The filum terminale is an anchor for the inferior
end of the spinal cord and spinal meninges
Dura Mater
 Makes 4 important folds in the cranial cavity
o Tentorium cerebelli
o Falx cerebri
o Diaphragma sellae
o Falx cerebelli
Tentorium cerebelli
 Boundaries
o Anteriorly: attached to clinoid processes
o Posteriorly: attached to the parietal bone and occipital bone
o Laterally: attached to the petrous part of the temporal bone
 Divides cranial cavity into supratentorial and infratentorial
o Infratentorial structures: midbrain (protrudes through notch and
connects with cerebral hemisphere), pons, medulla, cerebellum
o Supratentorial: houses cerebral hemispheres

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Falx Cerebri
 Boundaries
o Anteriorly: connects with crista galli
o Posteriorly: connects to tentorium cerebelli (becomes continuous
with it)
 Note- passes through Intracerebral fissure (aka longitudinal fissure)
between both hemispheres of the brain
 Divides the supratentorial cavity into R and L halves
 Purpose: mainly prevents the excessive movement of the brain within the
cranial cavity
Diaphragma sellae
 Present superior to the sella turcica
 The hole in this dural fold (red) allows communication between the
hypothalamus and the pituitary (blue; drawn on right)
o So the pituitary is below it, hypothalamus above, and the
pituitary stalk passes through
Note (Moore p. 867):
 Falx cerebri (L. falx, sickle-shaped)—the largest dural infolding, lies in the
longitudinal cerebral fissure that separates the right and the left cerebral
hemispheres
o The falx cerebri attaches in the median plane to the internal surface of
the calvaria, from the frontal crest of the frontal bone and crista galli of

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the ethmoid bone anteriorly to the internal occipital protuberance

posteriorly
o It ends by becoming continuous with the tentorium cerebelli.
 Tentorium cerebelli— the second largest dural infolding, is a wide
crescentic septum that separates the occipital lobes of the cerebral
hemispheres from the cerebellum
o The tentorium cerebelli attaches rostrally to the clinoid processes of
the sphenoid, rostrolaterally to the petrous part of the temporal bone,
and posterolaterally to the internal surface of the occipital bone and
part of the parietal bone.
o The falx cerebri attaches to the tentorium cerebelli and holds it up,
giving it a tent-like appearance (L. tentorium, tent)
o The tentorium cerebelli divides the cranial cavity into supratentorial
and infratentorial compartments
 The supratentorial compartment is divided into right and left
halves by the falx cerebri
o The concave anteromedial border of the tentorium cerebelli is free,
producing a gap called the tentorial notch through which the
brainstem (midbrain, pons, and medulla oblongata) extends from the
posterior into the middle cranial fossa
 The falx cerebelli is a vertical dural infolding that lies inferior to the
tentorium cerebelli in the posterior part of the posterior cranial fossa
o It is attached to the internal occipital crest and partially separates the
cerebellar hemispheres.
 The diaphragma sellae, the smallest dural infolding, is a circular sheet of
dura that is suspended between the clinoid processes forming a partial roof
over the hypophysial fossa in the sphenoid
o The diaphragma sellae covers the pituitary gland in this fossa and has
an aperture for passage of the infundibulum and hypophysial veins.
Dura Mater and pain

 The brain itself does not have pain receptors, but the dura mater very
sensitive to pain
o So if the dura mater is stretched it will  severe pain
Nerve Supply of Dura Mater
 Divided into Supratentorial (anterior/middle cranial fossa) and
Infratentorial (posterior cranial fossa)
Supratentorial
 Falx cerebri: CN V1 (anterior meningeal and meningeal branches of
ophthalmic division)
 Clinical: anterior cranial fossa referred pain will be in ophthalmic
region (forehead); middle cranial fossa refers to maxillary region; i.e.
from tumor
Infratentorial
 Floor of posterior cranial fossa: C2/C3
 Clinical: referred pain to back of pain/neck; i.e. from tumor

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Meningeal Layers (Recap of basics)

Pia mater (soft mother)- first covering surrounding the brain
 It is highly vascular
 Very delicate, thin, and closely covers contents of the brain and spinal cord
Arachnoid mater (spidery mother)- outside the pia mater
 Has multiple arachnoid trabeculae between arachnoid and pia (i.e. in
subarachnoid space)
o These are a type of connective tissue
Dura mater (strong/tough mother)
 Outside the arachnoid, very tough
 2 layers:
o Fibrous/Meningeal layer— inner layer, dura proper
o Endosteal/Periosteal layer— outer layer, sticks very close to bone
 Between the skull and the dura mater is a potential space (under normal
conditions there is no space, but under pathological conditions a space can be
made)
Spaces in brain vs. spinal cord
Note: spinal dura mater lacks
 Epidural space
periosteal layer of cranial dura mater
o Cranial cavity: potential space
o Vertebral column: real space
 Normally contains loose areolar connective tissue, lymphatics,
and venous plexus

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Types of Intracranial Hemorrhage

Epidural hemorrhage (Dr. DeSantis note 4 pages later at bottom of page)
 Between the meningeal and periosteal layer of dura mater run the middle
meningeal arteries and veins
o Middle meningeal artery enters skull
via foramen spinosum
o The anterior branch runs beneath the
temporal bone (specifically the
pterion)
o Note— middle meningeal artery is a
branch of the maxillary artery, which
is a branch of the external carotid,
while the middle cerebral artery is a
branch of the internal carotid artery
 Trauma (fracture) to temporal bone 
laceration/rupture of middle meningeal
vessels  accumulation of blood between
skull and dura mater
 Clinical
o Head trauma without hemorrhage
usually does not produce LOC, but if it does, there is rapid recovery:
o In epidural hematoma you have a lucid interval, where the patient
either:
 Loses consciousness, recovers rapidly, then again begins
progressing into a lower level of consciousness:
 OR initially they are fine, but then after hours or days begin
losing consciousness
 Also called “talk and die” syndrome
o This is because the hematoma eventually
compresses brain tissue  increased ICP and
ultimately, herniation and death
 Imaging:
o CT scan will show visible hematoma
o The blood will be dense (lighter) than brain
substance
o Lens shaped hematoma seen, because the
dura mater adheres tightly to the skull on
either side of the hematoma
 However, blood does not pass points where the dura mater
adheres to sutural ligaments (in between bones of skull;
drawn above)
 These points are even more tightly bound
 Treatment: Surgery to remove clot
Subdural hemorrhage
 Cerebral veins- veins that drain blood from the cerebral
hemisphere

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o Passes through pia, arachnoid, and meningeal dura mater to drain into
the venous sinus (drawn on right)
 This vein is fixed (held tightly) by the meningeal dura layer
which it crosses
 These veins are also called bridging veins, since they make a
bridge between arachnoid and dura mater as they cross
 Trauma can rupture the bridging veins (e.g. deceleration injury)
o The relationship between the dura (which sticks tightly to bone) and
the arachnoid (which sticks tightly to pia and the brain) is suddenly
shifted, and the bridging veins are easily ruptured at the point at
which they enter the dural sinuses
o This occurs more often in the elderly, due to physiological cerebral
atrophy  more freely floating brain  bridging veins have increased
sensitivity to sudden shifts
 Note- can be acute (severe head trauma) or chronic (occurs in elderly)
o In chronic, venous blood oozes slowly and collects over a period of
weeks-months
 Patients may not even remember initial trauma (unlike in
epidural hematoma)
o In acute, high impact velocity is necessary, so it may also be associated
with subarachnoid hemorrhage and contusion
 As such, prognosis is worse than even epidural hematoma
 Imaging:
o Crescent-shaped hematoma, since blood can rapidly spread between
the dura and the arachnoid (i.e. subdural space)
o Not well localized, unlike epidural hematoma
 Clinical
o May produce symptoms after very long time
o May see unexplained fluctuating levels of
consciousness
o May have hx chronic anticoagulants
o Remember the insidious onset
Subarachnoid hemorrhage
 Spreads everywhere as blood mixes with CSF
 Causes
o Circle of Willis is present in the subarachnoid
space
 ~5% of people have berry
aneurysms (abnormal irreversible
dilations of the vessel wall)
 85% occur in anterior circulation (int. carotid artery branches)
 15% occur in posterior circulation (vertebral)
1. These berry aneurysms can spontaneously rupture, which accounts
for ~80% of cases of subarachnoid hemorrhage

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2. Arteriovenous malformations— congenital abnormality of

abnormal direct connections between arteries and veins, forming
a tangle of abnormal blood vessels
 Usually intraparenchymal bleed but can involve subarachnoid
space
 Lower bleed risk (1-4%/year) compared to berry aneurysm
 Clinical
o “Worst headache of my life”, sudden headache
o Raised ICP (Neil: blood in subarachnoid space adds volume)
 Diagnosis
o CT
o Lumbar puncture— RBCs (since subarachnoid space contains CSF)
 Make sure ICP is not high, or LP is contraindicated
Intracerebral hemorrhage
 Patients with chronic hypertension develop microaneurysms within the
brain
o Sometimes these will rupture
 A special feature of intraparenchymal hemorrhage is that it will lead to
neurological deficit (neurological function will be lost in area of the brain
suffering from hemorrhagic event)
 Note (Robbin’s):
o Hypertension is the risk factor most commonly associated with
deep brain parenchymal hemorrhages, accounting for more than
50% of clinically significant hemorrhages and for roughly 15% of
deaths among individuals with chronic hypertension.
o Arteriolar walls affected by hyaline change are presumably weaker
than are normal vessels and are therefore vulnerable to rupture. In
some instances, chronic hypertension is associated with the
development of minute aneurysms, termed Charcot-Bouchard
microaneurysms, which may be the site of rupture
o Charcot-Bouchard aneurysms, not to be confused with
saccular aneurysms of larger intracranial vessels in the
subarachnoid space, occur most commonly within the basal
ganglia.
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Density depends on the age of the blood. Recall that acute blood is hyperdense (see
Figure 5.19B) and therefore bright on CT scan. After 1 to 2 weeks, the clot begins to
liquefy and may appear isodense (see Figure 5.19C). If there is no further bleeding,
after 3 to 4 weeks the hematoma will be completely liquefied and will appear
uniformly hypodense (see Figure 5.19D). However, if there is continued occasional
bleeding, there will be a mixed density appearance resulting from liquefied chronic
blood mixed with clotted hyperdense blood. Sometimes, with mixed-density
hematomas, the denser acute blood settles to the bottom, giving a characteristic
hematocrit effect (see Figure 5.19E).

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Subarachnoid hemorrhage: Unlike subdural hematoma, blood can be seen on CT to

track down into the sulci following the contours of the pia
Rx: Berry aneurysms clipped or coiled; epidural/subdural/intraparenchymal

hematoma suctioned up and active bleeds cauterized; in intraparenchymal
hematoma, may not replace bone flap right away due to brain swelling (will need
second procedure to replace it); AVM is repaired with coil or fast-drying glue
Dr. DeSantis: There are two "versions" of an epidural. The one is completely outside of all dura layers/fibers and
truly is between the skull and the dura. The other "epidural" acts pretty similarly (that is its spread is limited to
some degree by resistance to splitting of the dural layers, but the hematoma IS actually occurring between layers
of the dura. This is becoming more commonly referred to (in some sources) as a "dural border hematoma"
(but IS considered a form of "epidural" hematoma). The blood "dissects open the dural border cell layer". It is still
called epidural, I presume, because there is still some dural tissue beneath (deep) to it so the blood is still outside
of some dural tissue, AND, it behaves more like an epidural hematoma than a subarachnoid (which accumulates
on a different time scale, in a different age group
Downloaded (older)
by Ayesha and acts differently clinically).
Khalid (ayeshakhalid_308@yahoo.com)
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VI. Cranial Nerve Basics

Olfactory bulb is superior to the cribriform plate
 Not a cranial nerve
 Olfactory nerve (CN I) is attached to the olfactory bulb
o 15-20 pairs of olfactory nerves
o Bipolar cells with peripheral and central processes
 Central processes bundle together to make olfactory nerve
o Extend from olfactory nasal mucosa (in upper most nasal cavity)
o Bundles of olfactory nerve fibers pass through cribriform plate and go
to olfactory bulb
 Where exactly is the olfactory nerve attached?
o In the olfactory bulbs of the telencephalon of the prosencephalon
 In the olfactory bulb, there are mitral cells
o The central bundles of olfactory nerve bind with mitral cells
o From there, central processes go down the olfactory bulb in an
olfactory tract
o Olfactory tract divides into 2 olfactory striae
 Lateral olfactory stria connects with temporal lobe (that
portion of the lobe concerned with olfaction)
 This is also called piriform cortex (primitive cortex present
over the uncus; inferomedial area of temporal lobe)

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Moore about CN I (Olfactory):

The cell bodies of olfactory receptor neurons are located in the olfactory organ (the
olfactory part of the nasal mucosa or olfactory area), which is located in the roof of
the nasal cavity, and along the nasal septum and medial wall of the superior nasal
concha (Fig. 9.6, p. 1062). Olfactory receptor neurons are both receptors and
conductors. The apical surfaces of the neurons possess fine olfactory cilia, bathed by
a film of watery mucus secreted by the olfactory glands of the epithelium. The
olfactory cilia are stimulated by molecules of an odiferous gas dissolved in the fluid.
The basal surfaces of the bipolar olfactory receptor neurons of the nasal cavity of
one side give rise to central processes that are collected into approximately 20
olfactory nerves (L. fila olfactoria), constituting the right or left olfactory nerve (CN
I). They pass through tiny foramina in the cribriform plate of the ethmoid bone,
surrounded by sleeves of dura mater and arachnoid mater, and enter the
olfactory bulb in the anterior cranial fossa (Figs. 9.2 and 9.3). The olfactory bulb lies
in contact with the inferior or orbital surface of the frontal lobe of the cerebral
hemisphere. The olfactory nerve fibers synapse with mitral cells in the olfactory
bulb. The axons of these secondary neurons form the olfactory tract. The olfactory
bulbs and tracts are anterior extensions of the forebrain.
Each olfactory tract divides into lateral and medial olfactory striae (distinct fiber
bands). The lateral olfactory stria terminates in the piriform cortex of the anterior
part of the temporal lobe, and the medial olfactory stria projects through the
anterior commissure to contralateral olfactory structures. The olfactory nerves
are the only cranial nerves to enter the cerebrum directly.

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The optic nerve is not a true peripheral nerve; rather an elongation of the
diencephalon (retina is also a derivative of the diencephalon)
 Histologically speaking they are central tracts- evidence:
o Fibers present in optic nerve lined by oligodendrocytes
o Optic nerves are not affected by diseases that affect purely PNS; but
are affected by diseases that affect purely the central tract such as MS
o So if someone asks where optic nerve attaches to CNS, answer is that
it itself is a part of the CNS!
 Lamina cribrosa sclerae is a porous area in the back of the eyeball, which
allows neurons to traverse from the retina through to the optic nerve
o Med dictionary: the perforated part of the sclera through which pass
the axons of the retinal ganglion cells to enter the optic nerve.
 Optic nerves reach optic chiasm, at which point they are called optic tracts
 They then cross, make their way down the optic tract, then reach the lateral
geniculate body (lateral to thalamus)
 From there, nerves go to the visual cortex as the optic radiation

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 Oculomotor (CN III) nerve fibers begin lateral to periacqueductal gray

matter
 They pass through structures across the midbrain (red nucleus, then
substantia nigra, and cerebral peduncles)
 Then move medially and exit from the medial side of the cerebral peduncles
(masses of gray matter which connect the brain stem with the cerebral
hemisphere) called the interpeduncular fossa
 Where exactly in the CNS is CN III attached?
o Anterior aspect of the midbrain at the level of the superior colliculus,
just anteromedial to the cerebral peduncle, exit out into the
interpeduncular fossa (CSF-filled space)
The initial component of the pupillary light reflex is a bilateral

projection from the retina to the pretectum. Pretectal neurons project
to the Edinger-Westphal nucleus, a small group of nerve cells that
lies close to the nucleus of the oculomotor nerve (CN III) in the
midbrain. The Edinger-Westphal nucleus contains the preganglionic
parasympathetic neurons that send their axons via the oculomotor
nerve to terminate on neurons in the ciliary ganglion. Neurons in the
ciliary ganglion innervate the constrictor muscle in the iris, which
decreases the diameter of the pupil when activated. Shining light in
the eye leads to an increase in the activity of pretectal neurons,
which stimulates the Edinger-Westphal neurons and the ciliary
ganglion neurons they innervate, thus constricting the pupil
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Trochlear Nerve (CN IV) has its nucleus inferior to the nucleus of CN III, but within
the midbrain
 Nucleus is present at the level of the inferior colliculi (gray matter connected
to auditory system)
 Its fibers move backwards, and it is the only CN to do so
o Emerges to the front from the back of the midbrain
Moore Trochlear Nerve (CN IV)

Functions: Somatic motor (general somatic efferent) to one extra-ocular muscle
(superior oblique).
Nucleus: The nucleus of the trochlear nerve is located in the midbrain, immediately
caudal to the oculomotor nucleus
The trochlear nerve (CN IV) is the smallest cranial nerve. It emerges from the
posterior (dorsal) surface of the midbrain (the only cranial nerve to do so), passing
anteriorly around the brainstem. It has the longest intracranial (subarachnoid)
course of the cranial nerves. The trochlear nerve pierces the dura mater at the
margin of the tentorium cerebelli, and passes anteriorly in the lateral wall of the
cavernous sinus (Fig. 9.8). CN IV then continues through the superior orbital fissure
into the orbit, where it supplies the superior oblique—the only extra-ocular muscle
that uses a pulley, or trochlea, to redirect its line of action (hence the nerve’s name).
Recap, CNIII vs. CN IV:

 Both have nuclei in midbrain
o CN III exits from the anterior aspect, within the interpeduncular fossa
at the level of the superior colliculus
o CN IV exits from the posterior aspect at the level of the inferior
colliculus

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Trigeminal Nerve (CN V) exits from the anterolateral part of the midpontine region
 It has two roots (sensory is superior; motor is inferior)
 Sensory is connected to the trigeminal ganglion anteriorly, and pontine
region posteriorly
o From there it has 3 divisions
 Ophthalmic (V1)— exits through Superior orbital fissure
 Maxillary (V2)— exits through foramen Rotundum
 Mandibular (V3)— exits through foramen Ovale
 All fibers of the motor root follow the mandibular division (muscles of
mastication); none follow either the maxillary or ophthalmic division
S = Sup. orbital fissure = Standing

R = foramen Rotundum = Room
O = foramen Ovale = Only
Trigeminal
Ganglion
The trigeminal ganglion is housed within a dural recess (trigeminal cave) lateral to the
cavernous sinus
Note— image has cut away portion of the dura and cavernous sinus
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(proprioception)
(Fine touch)
 Baroreceptors, Chemoreceptors
(Pain and temperature)
General Somatic
Efferent column 
General Visceral 
Efferent column

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Abducens/Abducent Nerve (CN VI) innervates the lateral rectus muscle of the eye
 CN VI, CN VII, and CN VIII exit at the pontomedullary junction
o As the #s of CN ascend, they exit more laterally (i.e. toward
pontocerebellar angle)
o To be clear— CN VI exits at the most medial aspect of the
pontocerebellar angle
Moore (CN VI):

Functions: Somatic motor (general somatic efferent) to one extra-ocular muscle, the
lateral rectus.
Nucleus: The abducent nucleus is in the pons near the median plane.
The abducent nerve (CN VI) emerges from the brainstem between the pons and the medulla
and traverses the pontine cistern of the subarachnoid space, the right and left nerves
straddling the basilar artery. Each abducent nerve then pierces the dura to run the longest
intradural course within the cranial cavity of all the cranial nerves—that is, its point of
entry into the dura mater covering the clivus is the most distant from its exit from the
cranium via the superior orbital fissure. During its intradural course, it bends sharply over
the crest of the petrous part of the temporal bone and then courses through the cavernous
sinus, surrounded by the venous blood in the same manner as the internal carotid artery,
which it parallels in the sinus. CN VI traverses the common tendinous ring (L. anulus
tendineus communis) as it enters the orbit, running on and penetrating the medial surface
of the lateral rectus, which abducts the pupil.

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Facial Nerve (CN VII)

During its course, CN VII traverses the posterior cranial fossa, internal
acoustic meatus, facial canal, stylomastoid foramen of the temporal bone, and
parotid gland. After traversing the internal acoustic meatus, the nerve proceeds a
short distance anteriorly within the temporal bone and then turns abruptly
posteriorly to course along the medial wall of the tympanic cavity. The sharp bend,
the geniculum of the facial nerve (L. genu, knee) is the site of the geniculate
ganglion, the sensory ganglion of CN VII (Fig. 9.10). While traversing the temporal
bone within the facial canal, CN VII gives rise to the: greater petrosal nerve, nerve
to the stapedius, and chorda tympani nerve.
Then, after running the longest intra-osseous course of any cranial nerve, CN
VII emerges from the cranium via the stylomastoid foramen; gives off the posterior
auricular branch; enters the parotid gland; and forms the parotid plexus, which
gives rise to the following five terminal motor branches: temporal, zygomatic,
buccal, marginal mandibular, and cervical. (To Zanzibar By Motor Car)
 passes through foramen lacerum

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Edinger-Westphal nucleus (CN III) 76
Lacrimatory nucleus (CN VII)
Superior Salivatory nucleus (CN VII)
Inferior Salivatory nucleus (CN IX)
B: In this view of the middle ear, the carotid (anterior) wall of the tympanic cavity has been removed.
The tympanic membrane forms most of the membranous (lateral) wall; superior to it is the
epitympanic recess, in which are housed the larger parts of the malleus and incus. Branches of the
tympanic plexus provide innervation to the mucosa of the middle ear and adjacent pharyngotympanic
tube; but one branch, the lesser petrosal nerve, is conveying presynaptic parasympathetic fibers to the
otic ganglion for secretomotor innervation of the parotid gland.
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Vestibulocochlear Nerve (CN VIII)

77

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Glossopharyngeal Nerve (CN IX)

78
Passes through foramen ovale with V3 
(and accessory meningeal artery)

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Vagus Nerve (CN X)

79
(aka ‘nodose
ganglion’)

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Nuclei: Sensory—sensory nucleus of the trigeminal nerve (somatic sensory) and

nuclei of the solitary tract (taste and visceral sensory). Motor—nucleus ambiguus
(somatic [branchial] motor) and dorsal vagal nucleus (visceral [parasympathetic]
motor)
The aortic arch baroreceptor axons travel within the vagus nerve (CN X)
Lateral view of brainstem:
Pre-olivary sulcus
Olivary body
Post-olivary sulcus
Pre-olivary sulcus: between olivary body and pyramids; anteromedial to olive

Post-olivary sulcus: between olivary body and; posterolateral to olive
 CN IX, X, XI (cranial portion) exit at this point (listed from superior to
inferior)
Note— CN XI spinal portion begins more inferiorly but moves upwards through the
foramen magnum and meets up with the cranial portion of CN XI
Olive (olivary body): contain olivary nuclei
 Inferior olivary nucleus: part of olivo-cerebellar system, mainly involved in
cerebellar motor-learning and function
 Superior olivary nucleus: part of the pons and auditory system, aiding in the
perception of sound

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Spinal Accessory Nerve (CN XI)
Functions: Somatic motor to the striated sternocleidomastoid and trapezius

muscles.
Nuclei: The spinal accessory nerve arises from the nucleus of the spinal accessory
nerve, a column of anterior horn motor neurons in the superior five or six cervical
segments of the spinal cord (Fig. 9.5).
The traditional “cranial root” of CN XI is actually a part of CN X. It may be united for

a short distance with the spinal accessory nerve (CN XI). CN XI emerges as a series
of rootlets from the first five or six cervical segments of the spinal cord. It joins the
CN X temporarily as they pass through the jugular foramen, separating again as they
exit. CN XI descends along the internal carotid artery, penetrates and innervates the
sternocleidomastoid, and emerges from the muscle near the middle of its posterior
border. Next, CN XI crosses the posterior cervical region and passes deep to the
superior border of the trapezius to descend on its deep surface, providing multiple
branches to the muscle. Branches of the cervical plexus conveying sensory fibers
from spinal nerves C2–C4 join the spinal accessory nerve in the posterior cervical
region, providing these muscles with pain and proprioceptive fibers.

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Hypoglossal Nerve (CN XII) Emerges from the pre-olivary sulcus 82
Functions: Somatic motor to the intrinsic and extrinsic muscles of the tongue (G.
glossa)—styloglossus, hyoglossus, and genioglossus.
The hypoglossal nerve (CN XII) arises as a purely motor nerve by several rootlets
from the medulla and leaves the cranium through the hypoglossal canal (Figs. 9.2
and 9.3). After exiting the cranial cavity, CN XII is joined by a branch or branches of
the cervical plexus conveying general somatic motor fibers from C1 and C2 spinal
nerves and somatic (general) sensory fibers from the spinal ganglion of C2 (Fig.
9.18). These spinal nerve fibers “hitch a ride” with CN XII to reach the hyoid
muscles, with some of the sensory fibers passing retrograde along it to reach the
dura mater of the posterior cranial fossa (see Fig. 8.13B, p. 997). CN XII passes
inferiorly medial to the angle of the mandible and then curves anteriorly to enter the
tongue
Palatoglossus
is supplied by
CN X (Vagus
nerve)

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The tentorium cerebelli has been removed and the venous sinuses have been
opened on the right side. The dural roof of the trigeminal cave has been removed on
the left side and CN V1, CN III, and CN IV have been dissected from the lateral wall of
the cavernous sinus.

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A few notes on entry/exit points of CNs:

CN I passes through cribriform plate
CN II passes through optic canal
CN III, CN IV, ophthalmic part of CN V, and CN VI pass through superior orbital
fissure
CN V
 Again, ophthalmic branch passes through superior orbital fissure
 Maxillary branch passes through foramen rotundum
 Mandibular branch passes through foramen ovale (as do motor fibers)
CN VII goes through internal auditory meatus
Venous Sinus Drainage
The ophthalmic veins drain into the cavernous sinus.
The superior petrosal sinuses run from the posterior ends of the veins making up
the cavernous sinus to the transverse sinuses at the site where these sinuses curve
inferiorly to form the sigmoid sinuses. Each superior petrosal sinus lies in the
anterolateral attached margin of the tentorium cerebelli, which attaches to the
superior border (crest) of the petrous part of the temporal bone.
The inferior petrosal sinuses also commence at the posterior end of the cavernous
sinus. Each inferior petrosal sinus runs in a groove between the petrous part of the
temporal bone and the basilar part of the occipital bone. The inferior petrosal
sinuses drain the cavernous sinus directly into the transition of the sigmoid sinus to
the IJV at the jugular foramen. The basilar plexus connects the inferior petrosal
sinuses and communicates inferiorly with the internal vertebral venous plexus.
Emissary veins connect the dural venous sinuses with veins outside the cranium.
Although they are valveless and blood may flow in both directions, flow in the
emissary veins is usually away from the brain.
Note— foramen cecum (of frontal bone) contains emissary veins to the superior
saggital sinus (recall ‘danger triangle of the face’ since infections of the nose and
nearby areas can be transmitted to the meninges and brain causing meningitis,
brain abscess, or cavernous sinus thrombosis)

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VII. In Depth Cranial Nerves

CN III— Oculomotor Nerve
 Basic course
o Originates in midbrain
o Passes through subarachnoid space, and cavernous sinus
o Then reaches the orbit to supply structures there
Oculomotor nerve in midbrain
 Originates at the level of the superior colliculus
o One nucleus with somatomotor fibers
o Another nucleus which gives parasympathetic (or visceromotor)
fibers
 Nuclei
o Main nucleus is located in anterolateral aspect of periaqueductal
grey matter
 Will supply most of the extraocular muscles, which are
voluntary, so we call them somatomotor fibers (general
somatic efferents)
 These fibers go through the red nucleus and the substantia
nigra
 They then pass through oculomotor sulci, exiting into the
interpeduncular fossa
o Edinger-Westphal nucleus (parasympathetic nucleus of CN III)
 Gives off parasympathetic fibers, which are part fo the
oculomotor nerve and thus travel with other fibers of CN III
(mentioned above)
 Can also call these general visceral efferents
 So we can say that the oculomotor nerve is a motor nerve composed of
somatomotor fibers and visceral motor fibers (parasympathetic)
- All the somatomotor fibers are

for extraocular muscles
- All the visceral motor fibers are
for intraocular muscles <-->
CN III has a close anatomical means
relationship with some arteries: wrong =
 Posterior switch
<-->

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cerebral artery is superior to CN III

 Superior Cerebellar artery is inferior to CN III
 Posterior communicating artery runs close to CN III
 Problems in any of these arteries can interfere with CN III
Passage of CN III through cavernous sinus
 Both visceral and somatic motor fibers pass through lateral portion of
cavernous sinus
 Before it exits the cavernous sinus, it divides into a superior division
and inferior division
o Superior division— somatomotor fibers
 Supplies superior rectus (LR6SO4) and levator
palpebrae superioris
o Inferior division— somatomotor + visceral motor fibers
 Supplies inferior rectus, medial rectus, and inferior
oblique
 Also carries presynaptic parasympathetic (visceral
efferent) fibers to the ciliary ganglion
 Postsynaptic fibers from this ganglion pass to the
eyeball in the short ciliary nerves to innervate
the ciliary body and sphincter pupillae
Side Note— what passes through the cavernous sinus?
 Enter into lateral wall
o CN III (oculomotor nerve)
 Superior division
 Inferior division
o CN IV (trochlear nerve)
o CN V1 (Ophthalmic division of trigeminal nerve)
 Lacrimal
 Frontal
 Nasociliary (travels between superior and inferior divisions of
CN III
o CN V2 (Maxillary division of trigeminal nerve)
 Enters more medially
o The internal carotid artery (‘cavernous’ segment, of course; but it is
traveling posteriorly, whereas the cranial nerves are traveling
anteriorly)
o CN VI (Abducens nerve)
 Sixth nerve = Sex nerve
 Not in the lateral wall with the rest, but inside the ‘room’
 As it runs anteriorly it moves laterally
How does the fibers within the inferior division run and what is their importance?
 Parasympathetic (visceral motor) are more peripheral and superior— green
 Somatic are more buried and medial— red
 This is important since compression (from uncal herniation, Pcomm
aneurysm), then visceral motor fibers fail first, somatomotor fibers fail later

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o Space-occupying lesions (subdural or epidural hematoma, supra-

tentorial tumors) may push structures from the medial portion of the
temporal lobe downwards
 They then irritate CN III, affecting parasympathetic fibers first
  fixed dilated pupil
 Eventually, somatomotor fibers fail too  eye looks down and out + ptosis
 Especially suspect herniation if you see other signs of increased ICP, such as
projectile vomiting, papilledema
Other conditions
 Microvessels supply the nerve (vasa nervosum)
o First parasympathetic then sentral fibers are supplied
 Diabetes mellitus  microvessel disease  narrowing of vessels
o Decreased blood flow means inner part is more affected
o In this case the somatomotor fibers fail first
Cavernous sinus pathology
 This can affect all of the nerves within the cavernous sinus
 Can be thrombosis (retrograde to cavernous sinus)
o Wiki: The highly anastomotic venous system of the paranasal sinuses
allows retrograde spread of infection to the cavernous sinus via the
superior and inferior ophthalmic veins
 Can also be a tumor
 Internal carotid artery aneurysm or rupture  caroticocavernous fistula
Rest of path of nerve
 Approaches superior orbital fissure (through which CN IV, CN V1, CN VI pass)
o Surrounding the superior orbital fissure anteriorly is an anular
tendinous ring formed by superior/inferior/medial/lateral rectus
muscles
o This ring divides the superior orbital fissure into 3 parts
 Inferior division gives off branches to: medial rectus, inferior rectus, inferior
oblique
Optic nerve + ophthalmic artery

6 = CN VI
L = lacrimal
Origin of levator F = frontal
palpebrae T= trochlear
superioris muscle
Origin of superior
Origin of superior oblique muscle
rectus muscle LFT
Origin of lateral 6 Origin of medial
rectus muscle rectus muscle
Superior branch
of CN III Origin of inferior
Nasociliary rectus muscle
branch of CN V1
Inferior branch
of CN III Origin of inferior
Downloaded by Ayesha Khalid (ayeshakhalid_308@yahoo.com) oblique muscle
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 Superior branch supplies levator palpebrae superioris and superior rectus

muscle
 Parasympathetic fibers go to ciliary ganglion after following the inferior
division of somatomotor fibers (which are headed to the inferior oblique)
o This short parasympathetic root goes to the ciliary ganglion, from
which post-ganglionic fibers emerge as short ciliary nerves
 These move forward between the sclera and choroid
 They give rise to the ciliaris muscle (helps the lens change its
shape)
 Some fibers also contribute to the constrictor/sphincter
pupillae
 To recap: Edinger-Westphal nucleus gave off pre-ganglionic fibers, which
went along the somatomotor fibers of CN III, this branched to the inferior
division  eyeball  95% fibers to ciliaris muscle, 5% to sphincter papillae
What is CN III relationship with levator palpebrae superioris
 Levator palpebrae superioris has a voluntary component (supplied by
somatomotor fibers of CN III) as well as an involuntary component
(sympathetic fibers)
o Where do the sympathetic fibers come from?
o When CN III passes through the cavernous sinus, the sympathetic
plexus on the internal carotid artery gives off some fibers which then
go to the involuntary component of the levator palpebrae superioris
o Sympathetic fibers only go with the superior division!
CLINICAL CORRELATES
 Types of fibers
o Somatomotor fibers (GSE)
o Visceromotor fibers (parasympathetic fibers; GVE)
 LR6SO4 not supplied by CN III
o Eye looks down and out (cannot elevate, adduct) due to functioning
lateral rectus and superior oblique
o Occurs with compression of CN III  damage of parasympathetic
fibers  “fixed, blown” pupil
 Ptosis (CN III also supplies levator palpebrae superioris  drooping)
o Occurs with DM and other vasculature causes  somatomotor fiber
damage (which supplies levator palpebrae superioris)

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CN IV— Trochlear Nerve

 Nucleus is present at the level of the inferior colliculus
o General somatic efferent (GSE) fibers originate from here
o This GSE column is an extension of the anterior horn of the spinal
cord; albeit discontinuous
 Present anterolateraly to periaqueductal gray matter (same area as CN III,
however at the level of inferior colliculus vs. superior colliculus)
 3 unique features of CN IV
o Fibers exit dorsally rather than laterally or ventrally (another
difference from CN III); longest intracranial course
o Most cylinder nerve with least amount of fibers/neurons of all CN
o Goes to contralateral superior oblique muscle; i.e. it decussates
Just like CN III (more medial), CN IV
(trochlear nerve) passes between the
superior cerebellar artery (passes
above) and the posterior cerebral
artery (passes below)
Note— passes through the superior

medullary velum (also called the
anterior medullary velum)
 This is still located dorsally— it
is only called ‘anterior’
medullary velum in relation to
the ‘posterior medullary velum’
Superior medullary velum (some sources say CN IV

decussation occurs here)
Note— frenulum veli is a raised white band passing
medially through the superior medullary velum
CN IV passes through lateral wall of cavernous

sinus along with CN III. Starts out inferior to CN
III, exits cavernous sinus superior to CN III
(they cross paths)
Note— CN V1 and CN V2 are inferior to CN III and

CN IV in lateral wall of cavernous sinus
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CN V— Trigeminal Nerve
A few items to recap

 Spinal tract of trigeminal system— pain and temperature sensory
information from Va1 through V3 going to spinal nucleus of CN V
 Fibers from the 3 CN V nuclei (mesencephalic, primary sensory, and spinal) -
 ventral posteromedial (VPM) nucleus of the thalamus
o These are ascending fibers and are called trigeminal leminisci or
trigeminothalamic tract
HY Neuro
pg. 90 6th
Edition!
Spinal tract of trigeminal system
This sensory information is General Somatic Afferent (GSA)— touch, pain,

temperature, proprioception
 ½ of head
 Almost full face (except small part of jaw)
 Cranial cavity (especially anterior and middle cranial fossa)
 Eyes (especially anterior surface of the eye like the cornea)
 Nose and paranasal sinuses
 Oral cavity (including gums and teeth)
 Touch, pain, temp sensation for anterior 2/3 of tongue
o Lingual nerve is a branch of V3 which is a branch of CN V
 External ear
o Supplied by CN V, CN VII, CN IX, CN X
Motor supply
 Muscles of mastication
o Temporalis
o Masseter
o Lateral and medial pterygoids
 2 tensor muscles

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o Tensor tympani (pulls tympanic membrane medially, makes it tense)

o Tensor vali palatini
 2 muscles in the floor of mouth
o Mylohyoid
o Anterior belly of digastric muscle
Interesting fact on myelination of trigeminal sensory root— oligodendrocytes
continue for 7mm outside of CNS to myelinate axon
 Those demyelinating diseases of CNS, like MS, will damage nerve root

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Trigeminal Reflexes
1. Corneal reflex
 Long ciliary branches from nasociliary division of CN V1 takes information
of corneal stimulation to the sensory root
o Specifically to the upper portion of the spinal nucleus
 This information traverse a connection to the facial nerve nucleus (CN VII),
where information then travels to the temporal branch, which supplies
orbicularis oculi  eyelid closure
 To perform the test, a wisp of cotton is applied to the cornea
Orbicularis oculi
Spinal nucleus of
trigeminal nerve
2. Jaw Jerk (CN V afferent and efferent)

 Monosynaptic— sensory neurons of the trigeminal mesencephalic nucleus
send axons to the trigeminal motor nucleus, which in turn innervates the
masseter
 This reflex is used to judge the integrity of the upper motor neurons
projecting to the trigeminal motor nucleus
 The mandible—or lower jaw—is tapped at a downward angle just below the
lips at the chin while the mouth is held slightly open
o In response, the masseter muscles will jerk the mandible upwards.
 Normally this reflex is absent or very slight
o However in individuals with upper motor neuron lesions the jaw
jerk reflex can be quite pronounced
3. Oculocardiac reflex (CN V1 afferent and CN X efferent)

 Decrease in pulse rate associated with traction [disambiguation needed]
applied to extraocular muscles and/or compression of the eyeball

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 The reflex is mediated by nerve connections between the ophthalmic branch

of the trigeminal cranial nerve via the ciliary ganglion, and the vagus nerve of
the parasympathetic nervous system.
o These afferents synapse with the visceral motor nucleus of the vagus
nerve, located in the reticular formation of the brain stem
o The efferent portion is carried by the vagus nerve from the
cardiovascular center of the medulla to the heart, of which increased
stimulation leads to decreased output of the sinoatrial node

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4. Lacrimation (CN V1 afferent, CN VII efferent)

 Afferent from trigeminal
o Upper portion sensory information carried by ophthalmic division
o Lower portion sensory information carried by maxillary division
o These go to the trigeminal ganglion, then to the sensory root
 Lacrimatory pathways are connected with the superior
salivary/lacrimatory nucleus
 Then, it follows the facial nerve in the internal acoustic meatus until it
reaches the geniculate ganglion
o Then splits into lacrimatory and salivatory divisions
o The lacrimatory division is also called the greater petrosal nerve
 The greater petrosal nerve runs in the middle cranial fossa until it reaches
the foramen lacerum, which it passes through
o Within the foramen lacerum is a bony canal which goes to the
pterygopalatine fossa
o The greater petrosal nerve then runs through the pterygopalatine
fossa
 The deep petrosal nerve is given off by the internal carotid plexus
o Deep petrosal (sympathetic), greater petrosal (parasympathetic)
o
Note (NCC): The greater petrosal nerve takes off at the genu of CN VII to the reach
the sphenopalatine (pterygopalatine) ganglion, where postganglionic
parasympathetic cells project to the lacrimal glands and nasal mucosa.

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Facial colliculus
CN VII— Facial Nerve
 Branchial motor nucleus of CN VII supplies the second branchial arch—
muscles of facial expression
 Lesions of facial nerve nucleus
o Present in lower pons
o High probability of affecting
CN VI nucleus since CN VII
loops around it
 The elevation produced by facial
nerve in lower pons is called facial
colliculus
 Note— the branchial motor fibers
are called facial nerve proper
 The other part of the facial nerve is
called the nervus intermedius,
and contains other types of fibers
o Superior salivatory nucleus HY Neuro pg 79-81 6th edition!
 Upper part— acts as lacrimal
 Lower part— acts as salivatory
 Preganglionic parasympathetic fibers from here go along with
the facial nerve proper (this bundle along with other fibers is
called nervus intermedius)

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Chorda tympani contains nerve

fibers which supply taste to
anterior 2/3 of tongue and fibers
that go to submandibular and
sublingual gland

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Summary of fibers
 Superior salivatory nucleus (GVE)
o Lacrimatory nucleus + salivatory nucleus
o Go together as part of nervus intermedius (which is in betwwen the
motor component of the facial nerve and CN VIII)
o These go to the geniculate ganglion of the middle ear
 Prior to arrival, lacrimatory fibers split into greater petrosal
nerve
 Go into the foramen lacerum where they receive
sympathetic fibers from internal carotid artery (deep
petrosal nerve)
 This nerve reaches the pterygopalatine ganglion
 From there, postganglionic fibers jump to the maxillary
nerve (CN V2) and then to the lacrimal branch of CN V1
and reach the lacrimal gland
 Salivatory fibers continue along with the facial nerve proper
(motor component) for a while
 GVE; traverse facial canal in middle ear, descend
downwards through facial canal, but exit from it
through the chorda tympani in company with gustatory
fibers (SVA)
 Eventually join with the lingual branch of CNV3
 Nucleus tractus solitarius (nucleus of solitary tract)
o SVA; travels along with salivatory fibers from superior salivatory
nucleus in chorda tympani
o Important point to remember: has its cell body in the geniculate
ganglion
 GSA: touch, pain, temp from the ear (innervates external ear sensation)
o Part of nervus intermedius
o Leave lower portion of facial canal and go to tympanic membrane and
external auditory meatus
o Can be involved in Ramsay Hunt syndrome caused by VZV infection of
geniculate ganglion
 Motor nucleus of CN VII (SVE)
o Branchial motor branch
o Passes through nervus intermedius  geniculate ganglion  facial
canal
 Some fibers exit to form nerve to stapedius muscle (loud
sounds  contraction, which reduces stapes movement 
attenuation/reduction of sound)
o Exits via stylomastoid foramen
o Passes through parotid gland then forms TZBMC branches +
Note— Herpes Zoster of geniculate ganglion can reach the auricular branch of the facial
nerve  herpes vesicles of tympanic membrane + possible hemorrhagic fluid
 Can compress other portions of the facial nerve  ipsilateral hemifacial paralysis
 Called Ramsay Hunt syndrome
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VIII. Herniation
Herniation Occurs when mass effect is severe enough to push intracranial

structures from one compartment to another
Types of herniation:
1) Subfalcine
- Cingulate gyrus herniates under falx cerebri
- Causes compression of the anterior cerebral artery (runs on medial surface)
which may cause contralateral leg weakness
- Usually no clinical associations
2) Central
- Downward displacement of brainstem
- Can be caused by any increased ICP, such as hydrocephalus
- MILD: CN VI traction  lateral rectus palsy  eyes down/out
- MODERATE: bilateral uncal herniation
- SEVERE: through foramen magnum
3) Transtentorial (Uncal)
- Triad:
- Blown pupil (dilated, unresponsive) due to compression of CN III
- Hemiplegia
- Note: Hemiplegia is paralysis of one side of the body.
Hemiparesis is weakness of one side of the body and is
less severe than hemiplegia)
- Normally see contralateral paralysis due to
corticospinal tract pyramidal decussation
- Kernohan’s phenomenon:
- However, sometimes the midbrain is pushed all the
way over until it is compressed by the opposite side
of the tentorial notch, producing hemiplegia that is
ipsilateral to the lesion!
- Compression of midbrain (paramedian artery) 
Duret’s hemorrhage (hemorrhage into midbrain and
rostral pontine tegmentum; can be fatal)
-Coma
- Possible compression of posterior cerebral artery (PCA) hemorrhagic
infarction of
occipital lobe
4) Tonsilar
-Cerebellar tonsils through foramen magnum
-Compression of medulla respiratory arrest, BP instability, death

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IX. Organization of the Brain + Epilepsy
Focal seizures (one area of the brain) may spread and involve both cerebral
hemispheres  generalized seizure
 Tonic-clonic seizure
 Usually originating from the frontal lobe
 Very difficult to differentiate from the primary generalized seizure
Generalized seizures
 Originate in a brain region  immediately spread and engage neuronal
network in both hemispheres
Types:
 Typical absence
o Sudden and brief lapse of consciousness without loss of postural
control
o Last for seconds; the consciousness returns suddenly without
postictal confusion
o Automatisms: blinking of the eyelids, chewing, clonic movement of the
hands
o The main types in 15-20% of epileptic children
o Associated with some genetic epilepsies
o May occur hundreds of times per day, usually unobserved by parents
and interpreted as ”daydreaming”, decrease in school performance
o Induced by hyperventilation
o EEG: generalized symmetrical 3/second spike-and-wave discharge
during the clinical absence
 Atypical absence
o Differences from typical absence:
 Consciousness lapse is longer

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 Motor signs more intense

 Usually associated with neuronal abnormalities and mental
retardation
 Less responsive to treatment
 EEG < 3/second
 Generalized tonic-clonic seizures (“Grand mal”)
o 10% of people with epilepsy
o Usually 1 minute in duration
o Premonitory symptoms (prodromal) distinct from the stereotypic
auras in focal seizures that generalize
o Tonic phase:
 20-30 seconds
 Tonus muscles, contraction of all muscles (expiratory  ictal
cry, cyanosis; jaw  biting of the tongue
 Sympathetic: tachycardia, hypertension, increase in pupillary
size
o Clonic phase:
 tonic contraction is interrupted by relaxation; relaxation
period increases until the end
o Postictal phase:
 Muscular flaccidity, unresponsiveness, excessive salivation,
incontinence, confusion, headache, fatigue, muscle pain
o Note, on EEG:
 Tonic is generalized high amplitude, fast spike activity
 Clonic has a spike-and-wave pattern
Tonic:
Clonic:
 Atonic seizures
o Sudden loss of the postural muscle tone  collapse, or just head drop
o Brief impairment of the consciousness
o EEG: generalized spike-and-wave  slow waves (loss of muscle tone)
 Myoclonic
o Myoclonus: sudden and brief muscle contraction of one part or the
entire body
o Similar to the jerking movement observed when falling asleep
o EEG: bilateral synchronous spike-and-wave activity during the
myoclonus
o Physiological- jerky movement when you try to fall asleep

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 Unclassifiable
o They can not be designed as focal or generalized until additional
evidence is gathered
o Example: Epileptic spasms
 Briefly flexion or extension of proximal muscle such as truncal
muscles
o EEG:
 Hypsarrhythmias: giant slow waves on a background of
irregular spikes
 During the contraction: suppression of the EEG background
(electrodecremental discharge)
o Electromyogram: rhomboid pattern
o Seen in infants due to immaturity of the nervous system
A few named seizure variants:

 When it starts at the fingers and progress proximally: Jacksonian march
o Followed sometimes by postictal paresis (Todd’s paralysis)
 Child with multiple seizure types, and seizures are difficult to control:
Lennox-Gestaut
 Focal seizures and hippocampal sclerosis: Mesial temporal lobe epilepsy
syndrome (most common form of epilepsy)
 Child with seizures and history of perinatal hypoxemia: Lennox-Gestaut
 Adolescent with seizures that respond very well to medication: Juvenile

myoclonic epilepsy
 Child with slow (less than 3 Hz) spike and wave forms on EEG, and impaired
cognitive function: Lennox-Gestaut
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Treatment for Seizures:

 Note: Ethosuxamide for absence

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somatosensory
Primary
somatosensory
X. Tracts of the Spinal Cord

Descending Motor Tracts
Corticospinal tract
 30% of fibers from primary motor cortex (precentral gyrus)
 30% of fibers from pre-motor/supplementary motor area
o Pre-motor area: involved in motor planning (consults with cerebellum
and sensory area to determine body position in order to correctly
generate a motor plan)
o Supplementary motor area— primitive, bilateral movements
 40% of fibers from primary sensory area (postcentral gyrus)!
 Located in lamina V
Neurocortical circuits. G, granule cell; H, horizontal cell; M, Martinotti cell; P,

pyramidal cell; S, stellate cell. Loops show synaptic junctions.
Note— pyramidal cell neurons

Downloaded in layer
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are also called Cells of Betz
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Other 109
smaller
Cells of Betz (only ~30,000 axons of 1 million on each side) neurons
 Much larger than other cortical cells
 Myelinated much more heavily; fastest cells
 Only found in the primary motor cortex (Brodmann’s area 4)
 Connect directly to α motor neurons vs. others which use
interneurons
o These interneurons of the spinal cord are called internuncial
neurons Internuncial muscle
neuron
Corticospinal tract axons run through posterior limb of internal capsule
 It is important to recognize that fibers converge here
o Ex: if lateral striate (lenticulostriate) arteries (off MCA)
are damaged in stroke, they can damage the internal capsule 
contralateral weakness
 If some fibers are destroyed (i.e. lesion or damage is higher),
we call it hemiparesis
 If all fibers are destroyed, we call it hemiplegia (more severe)
Visuo-spinal reflex (visual stimulus  change posture)

 Center located in superior colliculus
Spino-visuo reflex (step in mud then look down)
 Center also in superior colliculus
Tectospinal and spinotectal tracts— refer to tectum of midbrain (seen below)
Where do corticospinal fibers go

through midbrain?
 Crus cerebri (anterior part of
cerebral peduncle)
o Can be divided into fifths
 Central 3/5ths is
where
corticospinal
fibers pass
Corticospinal pathways get dispersed

in the pons (scattered) due to presence
of pontocerebellar fibers (which keep cerebellum updated)
 This is important since although a small lesion can cause a large motor deficit
at the internal capsule with compact fibers, when they are scattered in the
pontine area this is not the case
Then they compact again and go through medullary pyramids

 Corticospinal tracts are also called pyramidal tracts since they pass through
the pyramids

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 Then at the inferior pyramid most fibers move contralateral (called medial
motor crossing or pyramidal decussation); occurs at junction of medulla
and spinal cord
 90% undergo this pyramidal decussation (lateral corticospinal tract)
o These fibers that cross are referred to as the lateral corticospinal
tract
 Lesions above decussation produce contralateral motor
dysfunction
 Lesions below decussation produce ipsilateral motor
dysfunction
 10% do not cross and continue downwards until they reach the anterior
white commissure, where they synapse with motor neurons
o These fibers that do not cross are referred to as the anterior
corticospinal tract
Lateral corticospinal tract connects to limb muscles (lateral portion of anterior

gray horn)
 Important in voluntary movement; fine motor movement esp. of hands
Ventral corticospinal tract connects to axial muscles (medial portion of anterior
gray horn)
 Responsible for primitive movements
 They cross in cervical/thoracic area at anterior white commissure to
eventually end up in contralateral anterior horn
 Remember that supplementary motor area supplies these fibers (axial
movement)!
Basal ganglia
On the way down, corticospinal fibers make special connections:
 Collateral fibers from corticospinal tract back to cerebral
cortex (let them know what they’re going to do)
 With basal ganglia; let them know what they’re doing; basal
ganglia releases certain motor programs to adjust
background muscle tone for upcoming movement
 Red nucleus- throws down another pathway called
rubrospinal tract (adjusts background motor)
 Reticular formation keeps alertness; when motor
movement is started it activates cortex
 Vestibular nuclei; they adjust anti-gravity muscles
(extensors)
 Olivary nuclei; connects to cerebellum (which is constantly
updated with info)
Note: It is not fully myelinated until the end of the second year
(Babinski’s sign)
Transection above OR below decussation Vestibular

 Babinski sign nucleus
Red nucleus
Olivary
nucleus

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Lower motor neurons- neurons coming out of CNS and connected to NMJ
 Note: pre-ganglionic sympathetic and parasympathetic are NOT LMNs
 Note: not just coming out of spinal cord, but from anywhere in CNS (i.e.
including brainstem
Upper motor neurons- all neurons originating from upper level and descending to
connect to LMN (either directly or indirectly), and modifying activity of LMN
 Cortical (originate from cortex)
o Corticospinal tract
o Corticonuclear tract
 Regulates activity of lower motor neurons present in the
brainstem (i.e. cranial nerve nuclei)
 Subcortical
Now, the lower motor neurons coming out of the brainstem should also be
controlled by cortical activity
 Cannot be called corticospinal since not going to spinal cord
 Functionally does the same work though
 Called corticonuclear fibers/tract
o Corticomesencephalic, corticopontine, corticomedullary
 Those corticonuclear fibers which have special connections to
LMN in the medulla are corticobulbar fibers
There are other subcortical centers that also regulate the activity of LMN:
 From tectum (posterior midbrain) to spinal cord (tectospinal)
o Superior colliculus houses visuospinal reflexes (see a bird and move)
 Opposite reflex is spinovisual  spinotectal tract
 Ex: you step in mud and look down
o Inferior colliculus houses auditory reflexes (hear a boom and move)
 From red nucleus the rubrospinal tract (remember “rubro” = red)
o Descend to white column and enhance the tone of flexor system
 Help you to sit down; contralateral limbs
o ‘Friend’ of corticospinal, helps with initiating voluntary movement
 From reticular formation the reticulospinal tract (from pons and medulla)
o Reticular formation is made up of white and gray matter and extends
throughout midbrain
o Pontine reticulospinal tract (‘friends’ of vestibulospinal, also
increase tone of extensor muscles)
 aka ventral/medial reticulospinal tract
o Medullary reticulospinal tract enhance flexor tone
 aka lateral reticulospinal tract
 From vestibulonuclear complex (junction of pons/medulla) the
vestibulospinal tract
o 4 nuclei (superior, inferior, medial, lateral)
o Fibers go to anterior white matter  increases the tone of extensor
muscles
o Helps us stand up (use extensors to stand)

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Pyramidal vs. extrapyramidal tracts

 Pyramidal tracts (tracts which pass through pyramids of medulla)
o Corticospinal tract (actually decussates through medullary pyramids)
o Corticonuclear tract (does not pass through pyramid and stays in
brainstem but is still called pyramidal by classification)
o Together these are called the pyramidal system; grouped together
due to similar origin
 Extrapyramidal
o Subcortical tracts (rubrospinal , reticulospinal, olivospinal,
vestibulospinal)
 Pyramidal tracts are mostly for fine, voluntary movement; extrapyramidal
tracts control posture, tone, and certain lower reflexes
Mnemonic
 ViP makes you stand up (extensor muscles are anti-gravity muscles)
o V— Vestibulospinal (main one for extensors/standing)
o P— Pontine reticular nuclei (assists)
 Sit on Rubber Mat (flexor muscles are necessary to sit)
o R— Rubrospinal
o M— Medullary reticular nuclei

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Ascending Tracts
Gray matter- collection of cell bodies
White matter- collection of axons
Tracts- white mater in a bundle with common origin and termination; connect in
cephalo-caudal axis (ascending and descending tracts)
Association fibers- connect CNS anteroposteriorly (ex: frontal lobe with occipital
lobe)
Commissures- connecting CNS left-right
How does the brain receive information about touch?

 A mechanical must be converted to an action potential
 This is accomplished by neuronal receptors, which act as transducers
o May be free nerve endings or a special group of cells attached to nerve
endings
 This information is taken up to the brain via ascending tracts
o Higher level processing occurs
 Then, from higher centers, motor orders come down via descending tracts
Roots are pure (dorsal purely sensory, ventral purely motor)

 However- trunks are mixed, and rami are mixed
o Some sensory info goes to the ventral ramus, and some motor goes to
the dorsal ramus Unipolar neuron (remember dorsal root ganglion is
Spinal nerve classic ex.)
Posterior ramus Trunk
Anterior ramus
Dorsal funiculus (also called dorsal collumns)- made up of fasciculus cuneatus

and fasciculus gracilis
 Only contains ascending tracts (vs. lateral and anterior columns with
ascending and descending tracts)
 Dorsal column is the most modern tract system; anterolateral is primitive
o Dorsal columns are heavily myelinated/fast vs. anterolateral are not
o So sensations from dorsal column should be more well developed;
those in the anterolateral system should be crude sensations
o Dorsal column is very specialized; expressway has only 1 type of
vehicle (no horse-carts there)

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Anterolateral system
 Pain, temp, crude touch, tickling, itching, sexual sensations
 None of these need to reach super fast
Dorsal Column
 Proprioception (sensations from locomotive system)
 Fine touch is more easily localized than crude touch (i.e. needle vs. hand)
o People follow lanes more on an expressway than a dirt road
o This is also why pain and temp may not be as well localized as fine
touch, since it is taken by anterolateral system not dorsal column
 Especially in the case of dull pain
 2 point discrimination (touched at two separate but close points— CNS can
tell the difference vs. being touched in one spot)
In the dorsal column:

 Sensations from upper part of body are deposited laterally; lower part of
body deposited medially (add as you go up)
o Fasciculus cuneatus- upper; fasciculus gracilis- lower (legs are
graceful, think of ballerinas)
 These fibers are central processes of the first order unipolar
neurons present in the dorsal root ganglion (peripheral
processes extend from mechanoreceptors like Pacinian
corpuscle to the dorsal root ganglion)
 Note— this means if you were to make a section of the lower spinal cord, you
would only see fasciculus gracilis, and only at a higher section of spinal cord
would you see both!
 Dorsal column sensations are NOT crossed, i.e. ascend ipsilaterally (right side
has sensations from right side of body, left side has sensations from left side)
First order neurons’ central processes form funiculus (FG + FC), which terminate at
nucleus gracilis and nucleus cuneatus
 The cell bodies present in nucleus cuneatus and gracilis are second order
neurons
 This is when they cross to opposite side as internal arcuate fibers (arc
within the medulla); then go upwards in the medulla as right/left medial
lemniscus
o Lemniscus- flathead bundle of axons
o Fasciculus- circular bundle of axons
Dorsal-column medial lemniscus pathway

 Major decussation in lower medulla
o Above that there is medial lemniscus carrying second order neurons
Medial
Second order neurons terminate in the thalamus (and 3rd order neurons originate)

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 Ventral anterior, ventral intermediate, and ventral posterior nuclei within

the ventral lateral area
 Ventral posterior has a lateral “mama”(VPL) and a more medial “baby” (VPM)
 Head/neck sensations go to VPM (ex. taste), but most other sensations go to
VPL, including medial lemniscus!
o In fact, second order neurons actually terminate in VPL
 From there, fibers move laterally to posterior limb of internal capsule 
they fan out of internal capsule as corona radiata
 They then get connected to post-central gyrus (primary sensory area)
Types of corpuscles giving sensory information:

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Pain
Peripheral nerve fibers (take pain from free nerve endings) and temperature
receptors (we will discuss pain, but thermal pathways go through the same
anatomical system):
 Aδ- more myelinated
 C- not myelinated
Fast pain vs slow pain:
 Fast pain is pinprick pain, carried by Aδ
o Perceived by CNS within 0.1 seconds
o Usually a mechanical or thermal stimulus via skin
 Diffuse pain, burning pain, throbbing pain, etc carried by C fibers
o Felt after 1 hr or more
o Can be produced by mechanical, thermal, or chemical (unique to C
fibers)
 What causes pain? Injury to tissue! What chemicals are sensed however?
o Bradykinin
o 5Hydroxytryptamine (5HT = serotonin)
o Histamine
o Acids
o K+ (spills out of injured cells)
o 2 more substances (cannot directly produce pain, but can reduce the
threshold for pain; i.e. if present, very little of aforementioned
substance required produce pain, and vice versa)
 Prostaglandins
 Substance P

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Fast pain localized vs. slow pain not as much

 Ex: hit yourself with hammer- easy to localize
 Ex: osteoarthritis- hard to localize
Why is slow pain diffuse vs. fast pain localized?
 Fast pain has a few neurons converging onto a few neurons (straight road
means you know the car started from point A in order to reach point B)
 Slow pain has few neurons converging onto many neurons (branched road
means you cannot localize which of paths A-F was used to reach point B)
How is pain reduced by extra stimuli (liniments, low level electrical stimulation,
acupuncture, massage, etc)?
 Other neurons going up (for example fine touch from dorsal column) give off
collaterals
o Through them there are connector neurons
o That means the collateral pathway, if stimulated enough, will activate
connector neuron which may release inhibitory neurotransmitters to
inhibit pain activity
o But if you stop that activity, again pain will become fully activated
o This theory is called gated theory (essentially that other stimuli may
reduce pain)
o
There are some special connections:
 Cingulate gyrus- emotional area (superior to corpus callosum; medial)
o Brings an emotional component to the pain (special connections to it)
 Insular cortex- brings an autonomic response to pain
Enkephalins and endorphins are released by the descending analgesic system

(periventricular area, periacqueductal area, other midline nuclei from brainstem),
inhibiting pain transmission
 Pain is heavily influenced by emotion
Important Concepts in Pain

1) Transmission- tracts involved, etc.
2) Perception- emotional component; circumstance
3) Modulation- gating theory, descending analgesic system

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First order neurons have their cell bodies in the dorsal root ganglion (similarity
between anterolateral and dorsal systems)
 These terminate in dorsal gray horn, specifically in the substantia
gelatinosa
 Before they terminate, they either ascend or descend
o This ascension/descension at every level forms a sort of local tract
o This is called the dorsolateral tract of LISSAUER
 This tract is made of 1st order neurons’ central processes as
they enter the spinal cord
 They then connect to second order neurons
 Note: in anterolateral system, second order cell bodies are
present in dorsal horn of spinal cord vs dorsal system in FG & FC
o The areas where these are present (dorsal horn) are
called substantia gelatinosa (lamina II)
o In subtantia gelatinosa, glutamate and substance P are
released by nerve endings to stimulate 2nd order neuron
 Second order neurons then cross over to contralateral side and
run upwards
o Neurons from upper body are added medially
o This tract which has formed on the contralateral side is
the lateral spinothalamic tract (pain, temp)
Aδ fibers Dorsal column pathway

for comparison
C fibers
 Crude touch has the same pathway until it reaches dorsal horn
o Then, it crosses to anterior commissure and runs superiorly
 This tract is called anterior spinothalamic tract (crude
touch)
Axons of first order neurons for dorsal column medial lemniscus pathway enter spinal cord, turn
and ascend in ipsilateral dorsal columns all the way up to medulla, where they synapse on
neurons in the dorsal column nuclei. The axons of neurons in the dorsal column nuclei then cross
the midline and ascend to the contralateral thalamus. In contrast, the crossing point for
information conveyed by the anterolateral system lies within the spinal cord. First order
neurons contributing to the anterolateral system terminate in the dorsal horn (after
ascending/descending 1-2 segments in Lissauer’s tract), and second-order neurons in the dorsal
horn send their axons across the midline and ascend to the contralateral side of the cord (in the
anterolateral column) to their targets in the thalamus and brainstem. Because of this
anatomical difference in site of decussation, a unilateral spinal cord lesion  dorsal
column symptoms ipsilaterally (loss of touch, vibration, pressure, proprioception) and
anterolateral symptomsDownloaded
contralaterally (loss(ayeshakhalid_308@yahoo.com)
by Ayesha Khalid of pain, temperature sensation)
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Now, these tracts go to the medulla

 In between these two (anterior and lateral spinothalamic tracts) is the
spinotectal tract, for spinovisual responses
 They all join up in the medulla to run up as a single bundle
o Called the spinal lemniscus
o However, spinotectal tract branches off at tectum before reaching the
thalamus
 The other two (lateral and anterior spinothalamic tracts) go to VPL
o Information of fast pain (Aδ) goes to VPL
o Slow pain fibers
 Some are connected to VPL
 But majority go to intralaminal nuclei of thalamus
 Slow pain also intensely stimulates the reticular formation (a
mixture of white/gray matter, extending through midbrain)
 Reticular formation is the main on/off switch of the brain-
keeps cerebral cortex active (in sleep everything works but
cerebral cortex is not receptive due to reticular formation)
 ALL sensory info going upwards connects to reticular
formation, but heavy stimulation comes from the pain
pathway (ex: strong pain stimulus does not let you sleep!)
 Now, from VPL they go through posterior limb of internal capsule  corona
radiata  central gyrus

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More Tracts…
Information from spinal cord to cerebellum is spinocerebellar tract
 Ipsilateral, vs. anterolateral and dorsal system (which connect to
contralateral cerebrum)
 2 main spinocerebellar pathways
o Dorsal spinocerebellar pathway
 Carries info from pressure receptors, muscle spindles, golgi
tendon organs
 These fibers terminate in the dorsal horn- Clarke’s nucleus
(lamina VII)
 Second order neurons move ipsilaterally into the white matter
(lateral column)
 Go upwards from lateral column
Side note: Connections to cerebellum:

 Medulla: inferior cerebellar peduncle
 Pons: middle cerebellar peduncle
 Midbrain: superior cerebellar peduncle
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Dorsal spinocerebellar pathway:

 First order neurons terminate in dorsal root ganglion
o Especially from C8-S3
 Clarke’s nucleus extends from C8-L3 (so lower fibers must
extend upwards to reach Clarke’s nucleus in L3)
 From Clarke’s nucleus they begin going upwards to
cerebellum
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Accessory Cuneate nucleus

 Receives from upper body, whereas Clarke’s receives info from lower part of
body
 Note: NOT to be confused with cuneate fasciculus
 Called cuneocerebellar pathway
Anterospinocerebellar pathway (or ventralspinocerebellar pathway)

 Second order neurons cross
o But they are supposed to stay on the same side! What to do?
o They go to superior cerebellar peduncle, then turn back and re-cross
Most tracts covered, but here are 3 minor ones:
 Spinotectal pathway- crosses on entry
o Gets joined by lateral/anterior spinothalamic tracts, becomes part of
spinal lemniscus
 Spino-olivary pathway
o Olive is mass of gray matter in medulla
o First order neuron in dorsal root ganglion, second order neuron in
gray horn, second order neuron’s extension went to white column and
ascended as spino-olivary tract
o From there, info goes to cerebellum
o Info is proprioception, touch, pressure (functionally similar to
spinocerebellar pathway)
 Spinoreticular pathway
o Stimulates reticular formation and stimulate cortex  alertness
Note: if proprioception ascending is only info given, still depends on whether it is
going to conscious level or unconscious level
 Conscious  dorsal column medial lemniscus pathway
 Unconscious  spinocerebellar

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XI. Basal Ganglia

 Ganglia is actually a misnomer, since ganglia is actually a collection of cell
bodies outside the CNS
o But of course, basal ganglia are present within the CNS, so they are
more correctly referred to as the basal nuclei
o Nuclei are collections of cell bodies (i.e. gray matter) within CNS
surrounded by white matter
 Thalami are located medially, above midbrain
o Superior and wrapping around them are masses of gray matter
curved in a “C” shape called caudate nuclei
 Ventral striatum— region where the putamen fuses with the caudate
o Most of the ventral striatum is called the nucleus accumbens, an
important component of limbic circuitry
 Internal capsule (bundle of axons; cortical fibers descend, other fibers
ascend)
o Anterior limb— passes between lentiform nucleus (putamen and
globus pallidus) and the caudate
o Posterior limb— passes between lentiform nucleus and the thalamus
o Note— caudate and thalamus are always medial to the internal
capsule, while the lentiform nucleus (globus pallidus + putamen)
is always lateral to the internal capsule
Series of images (Lateral to Medial):

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Notice that the caudate

nucleus forms connections
with the putamen through
the internal capsule— this
gives it a striped
appearance = striatum
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Amygdaloid
body
 Lateral to the putamen is the external capsule

 More laterally there is a thin sheet of gray matter called claustrum Finally,
there is an extreme capsule
 Insula is lateral to that; it is the region of the cerebral cortex buried within
the depths of the lateral fissure
o Appears as an island of cortex (insula = island)
 Substantia nigra is located in the anterior midbrain
o Posterior portion is dark and tightly pack = pars compacta
 Contains darkly pigmented dopaminergic neurons
o Anterior part is not as tightly packed = pars reticulata
 The mass of gray matter at the end of the tail of the caudate is the amygdala
(amygdaloid body)
 Corpus striatum— refers to lentiform nuclei and caudate
o Striatum
(neostriatum—
putamen + caudate
o Paleostriatum—
globus pallidus

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XII. Brainstem Basics— Midbrain, pons, medulla
Cerebral peduncles— connect brainstem with forebrain

Cerebellar peduncles— bundles of white matter that connect the brainstem to the
cerebellum
 Superior cerebellar peduncle— connects midbrain to cerebellum
 Middle cerebellar peduncle— largest; connects pons to cerebellum
 Inferior cerebellar peduncle— connects medulla to cerebellum
In order to understand X-sections of brainstem, you must know CNs and their nuclei
 Nuclei:
o Above midbrain: I (telencephalon), II (diencephalon)
o Midbrain: III, IV
o Pons: V, VI, VII, VIII
o Medulla: IX, X, XII
o Spinal cord: XI
 CNs (look at diagram below)
 Make sure you understand the brainstem from all views (especially ventral
and dorsal)
A few clinical tie-ins based on anatomical locations

of CNs
 Lateral pontomedullary junction
(pontocerebellar junction) lesion  CN VII and
VIII affected
 Lesion in medial pontomedullary junction  CN
VI affected
 Note— CN VII fibers wrap around CN VI nuclei,
so if there is a lesion in that location it will
affect CN VI and CNVII

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Basic portions of midbrain:
DORSAL
VENTRAL
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What should be present in the midbrain?

1. Ascending system (all ascending tracts)
2. Descending system (all descending tracts)
a. Down-going systems should be the most anterior, so they pass
through the basis
i. Corticospinal fibers, corticonuclear fibers
3. Cerebellar system (remember that there are posterior connections to the
cerebellum)
4. Cranial nerve systems
What changes are there from spinal cord to medulla?

 Spinal canal widens  4th ventricle
o Ascending and descending tracts have major crossings in the medulla,
which breaks up gray matter into small pieces, called nuclei
o Gray matter: sensory components form nuclei laterally, motor move
medially to form nuclei
4th ventricle
S = sensory
M = motor
 Ascending tracts
o Some are pushed laterally, some anteriorly
o Note— supplementary motor gray matter sits between descending
tracts and lateral ascending tracts
 What are these supplementary motor areas?
 In medulla: olivary nucleus
 In pons: pontine nuclei
 In midbrain: red nuclei, substantia nigra
Motor nuclei Branchial motor
Sensory nuclei
Lateral Ascending
tracts
White space is reticular
formation, mixed
gray/white (should be
shaded)
Supplementary motor
Descending tracts gray matter
Downloaded by Ayesha Medial ascending tracts

Khalid (ayeshakhalid_308@yahoo.com)
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XIII. Vestibular System

 The vestibular system is a special somatic afferent (SSA) system concerned
with balance, posture maintenance, and coordinating vestibule-occular
reflexes
 3 semicircular canals posterior to the cochlea
o superior (also called anterior)
o posterior
o lateral
Basically, the semicircular canals, cochlea, and vestibule are all networks of bony
canals
Fluid within the membrane is called endolymph, outside the membrane is called
perilymph
Membranous portion of the cochlea becomes the saccule (anteroinferior), and then
the utricle
 Made up of membranous structures housed within the vestibule
In the semicircular canal there is a semicircular duct

 Lateral, anterior, and posterior duct
 They all have perilymph (between bony and membranous sytem)
 Membranous cochlear duct has sensory epithelium present on the basilar
membrane called the organ of Corti

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Perilymph flows into semicircular canals as well (it also has membranous areas)
Sensory epithelium:
 In the cochlea they are concerned with hearing, and are called organ of Corti
 In the utricle/saccule they play a role in static balance, and are called
macula
 In the semicircular canals they are for kinetic balance, and are called crista
(located within the ampulla)
Summary:
 Bony structures  membranous structure  sensory epithelium  function:
o Cochlea  cochlear duct  organ of Corti  hearing
o Vestibule
  Utricle  macula  static balance/linear acceleration
  Saccule  macula  static balance/linear acceleration
o Semicircular canals  Semicircular Ducts  Crista  kinetic
balance/angular acceleration

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 Sensory epithelium of the utricle is located on the floor, but sensory

epithelium of the saccule are located on the wall (That sensory epithelium is
called the macula)
 Below this are neurons that carry sensory info to the CNS
o Their cell bodies are located in the vestibular ganglion
o 1st order neurons have peripheral processes which go to macular
structures, and central processes make the vestibular nerve
(connected at pontomedullary junction, laterally, with vestibular
nuclei and not with cochlear nuclei)
 There is a similar structure present in the ampulla of the semicircular canal,
called cristae
o There are neurons connected to the cristae, also taking info to the CNS
o Their cell bodies are in the vestibular ganglion
 Sensory neurons from the utricle, saccule, and semicircular canals make the
vestibular nerve
o 3 cristae (lateral, anterior/superior, posterior semicircular canals)
o Macula of utricle
o Macula of saccule
Enlarged macula/more detail:

 Sensory epithelium is supported by supporting cells (located underneath)
 On top, there are long kinocilia (clubbed at the end) with surrounding
consistently shorter stereocilia
 When stereocilia move toward kinocilia, the cell depolarizes
o Vice versa
 However, in reality, some K+ efflux is constantly occurring
o Depolarization stops efflux, moving potential more positive
o Hyperpolarization increases efflux, moving potential more negative
The real question is- how do the cilia move?

 Above the cilia there is an otolith membrane, a gelatinous substance
 Within the otolith membrane are embedded otoconia (or otoliths, calcium
carbonate crystals)
 The stones move toward, whichever direction you tilt your head, exerting
gravitational pull as they do so
o You actually change impulse generation from the macula based on
which way you tilt your head
o i.e. the pattern of electrical stimulation is altered
o if you close your eyes you can tell where you are; and even if the car
accelerates you can tell because the stones move backward; brakin gin
a car the stones keep moving forward while the macula stops and the
pattern of electrical stimulation will alter
 Macula work in static balance and linear acceleration
Comparison of cochlear and vestibular system:

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Cochlear system Vestibular system

Bony canals Vestibule
Cochlear duct Utricle/saccule
Organ of Corti Macula
Vibration of basilar membrane Otoconia affect cilia
Tectorial membrane bends cilia Gelatinous layer
Remember that the sensory epithelium of the utricle is located on the floor, but the
sensory epithelium of the saccule are located on the wall
 This is because the utricle responds to horizontal acceleration
 The saccule responds to vertical acceleration
 If this is confusing, imagine the direction of the hairs bending rather than the
sensory epithelium as a unit
How do the cristae work? We’ll talk about the cristae of the right lateral semicircular
duct
 Firstly, cristae are a specialized epithelial system present in the ampulla of
the semicircular duct
o Contain supporting cells as well
 Fluid movement produces a drag on the sensory epithelium
 If you move to the right, the right side will be stimulated/depolarize
o i.e. stereocilia are bending toward the kinocilium (kinocilium are
more medial, fluid moves lateral to medial); rate of impulse
generation increases
o The left side will undergo hyperpolarization, with increased rates of
K+ loss; rate of impulse generation decreases
 The sensory epithelium (hair cells) are covered by a jelly-like substance
called the cupula (moving of the fluid move the cupula)
 So basically, angular head movement alters fluid movement in the 3 cristae
on either side of your head
o When the rate of bending alters, it alters the rate of firing
If you suddenly stop, fluid will keep moving, as if you are going in the opposite
direction
All semicircular ducts open into the utricle

 The lateral semicircular canal has its own openings (2)
 The superior/anterior and posterior semicircular canal share an opening
Input of vestibular nerve goes to vestibular nuclei (has lateral, superior, medial, and
inferior divisions)
 From there it goes to flocculonodular lobe, since the cerebellum needs to be
informed, via the juxtarestiform body

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 The fastigial nucleus receives information from the vestibular nuclei

 The vestibulospinal tract (from the vestibular nuclei) is important in
standing (remember ViP)
o When the vestibulospinal tract reaches the spinal cord it stimulates
extensor α motor neurons, and inhibits flexor α motor neurons
The rubrospinal tract (arises from the red nucleus), in contrast, is important for
sitting (sit on a rubber mat)
 It also is involved in wrist movement
General Principle: As you move inferiorly in the CNS, tracts are controlling more
proximal musculature; as you go superiorly, tracts are controlling more distal
musculature
 Ex: corticospinal tract controls very distal and fine movement, and
vestibulospinal controls relatively proximal/gross movement
(antigravity/extensor muscles)

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XIV. Auditory System

Basic Structure of the ear:
 From the pinna (or auricle) there is a cavity going inwards called the
external auditory meatus
o Terminates in the middle ear, which contains the tympanic membrane
and the ossicular chain (malleus incus stapes)
 More medially there is the inner ear, which consists of two parts
o Cochlea (fluid filled)
o Vestibule (with multiple semicircular canals- lateral, superior,
posterior)
 Internal auditory meatus is more medial to that
o Through it there are two nerves
 CN VII (Facial)
 Goes to middle ear
 CN VIII (Vestibulocochlear)
 One part goes to cochlea- hearing
 One part goes to vestibule/semicircular canals- balance
Path of sound:
 Pinna collect sound waves
 External auditory meatus funnels to middle ear, where the ossicular chain
takes input through the oval window
 This then moves to the fluid filled cochlea
o Sensory structure within cochlea converts sound energy to
electrochemical action potentials
 They are called organ of corti
o Then taken by the CN
 These structures (outer, middle, and inner ear are housed in the temporal
bone)
Note: from the middle ear there is a Eustachian tube (tubotympanic tube) that
opens into the pharynx. There is also an aditus to mastoid antrum which projects
from the middle ear
Summary so far:
 Middle ear laterally has the tympanic membrane and external ear
 Middle ear medially has the middle ear
 It is a
Middle view:
 The external auditory meatus produces wax
o This wax acts as a bug repellent
o It can accumulate too heavily, however, producing conductive
deafness

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 The middle ear has four components: anterior, posterior, roof, and floor
o The roof of the middle ear is very thin
 So many times, a destructive infectious process may break
through and enter the middle cranial fossa
 It must also break through a thin bone called tegmen
tympani
 This infectious can produce meningitis, and brain
abscesses (especially in the temporal lobe, think about
location of the middle ear)
 Note: infection of the ear is the second most common form of meningitis after
meningococcal infection (which goes through the throat, and may go through
the blood)
 Note: the most common cause of brain abscesses (especially of the temporal
lobe) is middle ear infection
If you drill downwards from the middle ear, where will you end up?
 Bulb of the internal jugular vein
 Remember also that CN IX, X, and XI go through the jugular foramen
 So, if the infection goes downwards it can cause infection to go into the main
drain of the CNS (internal jugular vein)
o However since the floor is much stronger than the roof, this is not
common
Pharyngeal infections can travel to the middle ear via the Eustachian tube
 Normally the middle ear is and air filled cavity
 However, if the Eustachian tube is closed due to swelling of the pharyngeal
mucosa in infection…
o The middle air becomes filled with fluid; even the mastoid air cells are
depleted of air
o This stagnant fluid is vulnerable to infection
o The true purpose of the Eustachian tube is for air balance
 The pressure in the nasopharynx is the same as the external
environment
 The Eustachian tube is constantly equalizing pressure
On the lateral wall of the middle ear is the tympanic membrane

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 Lateral View ^
 You can see the handle of the malleus moving backwards
 The pars flaccida is superior
 The pars tensa is inferior
From a frontal view you can see that the mucosal membrane of the middle ear is
separated from the skin of the external ear/auditory meatus:
 Inferiorly by a thick connective tissue of the tympanic membrane
 Superiorly only by a very loose connective tissue of the tympanic membrane
 These are pars flaccida and tensa, respectively!
Some of the middle ear extends above the external auditory meatus
 The superior portion of the tympanic membrane, the pars tensa, is adjacent
to the handle of the malleus
 The malleus is attached to the incus, which is attached to the footplate of the
stapes
 This opens into the oval window, located on the medial aspect of the middle
ear
 Note: the middle ear acts as an amplifier of sound waves
 When the oval window pushes fluid down the chochlea, the round window
subsequently vibrates
 Note: the oval window is essentially the point where sound waves are
converted into fluid waves
o Also, middle ear is normally air filled
Normal, healthy ears hear sounds of 20-20,000 Hz

 Ordinary conversation is 300-3,000 Hz
There is special elastic tissue to hold the footplate of the stapes into the oval
window
 There may be neogenesis of bone in that area, which can cause deafness with
old age- called otosclerosis

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o Since it reduces conduction, it is a form of conductive deafness (as

are causes of deafness in the external ear)
 Causes of deafness from the inner ear, cochlear nerve, and central connection
are sensorineural deafness
There are two important muscles in the middle ear, which prevent movement of
ossicles
On the medial wall of the middle ear there is a facial canal (housing the facial
nerve) and a promontory (a bulge in the wall)
 This bulge is produced by the basal turn of the cochlea on the opposite side
of the wall (more medially)
 Posterior to the promontory is the oval window, and inferior to that is the
round window
 The lateral semicircular canal produces a bulge in the uppermost part of
the middle ear
Infection can cause:

 Facial nerve palsy by compression/destruction of the facial nerve (i.e. via
cholesteatoma which is a growth of squamous keratinizing epithelium
producing chronic suppurative otitis media, or CSOM, a condition with
chronic ear discharge through a perforated tympanic membrane)
 Vertigo- labrynthitis (aka otitis interna or vestibular neuronitis)
 Deafness (damage to oval or round window)
Now, the posterior wall has an opening, called the aditus to mastoid antrum
 It takes you to the system of mastoid air cells

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The mastoid air cells provide a reservoir of air

 The Eustachian tube equalizes pressure between pharynx and middle ear
 The tensor tympani muscle is just above the Eustachian tube and runs
through a canal
o The tendon wraps around a bony spicule (acting as a type of hook),
then turns laterally to reach/control the handle of the malleus
o When it contracts, it pulls the tympanic membrane inwards, which
makes it tense- hence called the tensor tympani
 Attached to the posterior wall is the stapedius muscle
o It holds the footplate of the stapes (the part closer to the incus) to
prevent excessive movement
Nerve supply:
 The motor part of the mandibular part of CN V (Trigeminal) supplies the
tensor tympani
o CN V palsy means tensor tympani cannot contract, but what happens?
 The loosened muscle can no longer pull the malleus, making
the tympanic membrane loose, causing the vibration to be
poorly transmitting and affecting hearing
 Poorly transmitted vibrations lead to hypoacusis
 CN VII (Facial) supplies the stapedius muscle
o CN VII palsy causes the stapes to become loose
o This causes hypervibration (remember function of stapedius)
o This produces hyperacusis
 Ordinary sounds producing extraordinary vibration; ordinary
sounds annoy you
Vestibule/Cochlea:
 Anterior and medial to middle ear
 Posterior to it is the vestibule
o It has a lateral, superior, and posterior semicircular canal
Meniere’s disease- affects low frequency sounds first, since apex is wound tighter
than the base
 Idiopathic disease of exclusion; caused by increased pressure of endolymph
(within vestibule)
 Administer HCTZ and low sodium diet
 Can also give steroids (intratympanic)

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XV. Visual System

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XVI. Cerebellum

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Dr. Najeeb Lecture Notes- Neuro

Transcribed and compiled by Neil Parikh

I. Neuromuscular Junction (NMJ) 2

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Resting membrane potential— transmembrane potential which does not fluctuate

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in out via the concentration gradient = # of K+ ions moving in via the

Resting Membrane Potential 2

Another name for equilibrium potential is Nernst potential

Equilibrium potential of human cells

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o Scientists called this potential resting membrane potential

 This is the potential difference across cell membranes of

What is the role of Na/K ATPases in resting membrane potential

Na+ channels in neuronal cell membranes

Resting Membrane Potential 3

Nernst Equation: E = RT log [Co]

R= universal gas constant

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Remember that k (constant) is -60mV, which is a calculated version of RT/F

Note— in a resting situation, the permeability of Na+ is zero, so it can be cancelled

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Summary of two different mechanisms of K+ affecting excitability of cells

Last Question: Hypernatremia vs. Hyponatremia

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Action potentials— electrochemical fluctuations in the cells membranes of

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o We say the membrane is depolarized, since it

Local Potential vs. Action Potential

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 Either it fires or doesn’t based on whether threshold Is reached

a— changes in membrane potential (mV)

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What factors determine the velocity of action potentials?

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The worst part of Guillain-Barré Syndrome classic cause of PNS demyelination;

Schwann cells vs. Oligodendrocytes

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 Stimulation of nicotinic AChRs at postsynaptic membrane  influx of Na+ 

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Clostridium Botulinum Toxin

 Myasthenia = weakness; gravis = serious

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Detailed pathogenesis of AChR autoantibodies

Role of thymic abnormalities in Myasthenia Gravis

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 However, the real danger in involvement of respiratory

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o Remember that these are mostly found in those with AChR