13 Neurology and Special Senses

HIGH-YIELD SYSTEMS
Neurology and
Special Senses
“We are all now connected by the Internet, like neurons in a giant brain.” `Èmbryology 474
—Stephen Hawking
`Ànatomy and
“Anything’s possible if you’ve got enough nerve.” Physiology 477
—J.K. Rowling, Harry Potter and the Order of the Phoenix
``Neuropathology 495
“I like nonsense; it wakes up the brain cells.”
—Dr. Seuss `Òtology 517
“I believe in an open mind, but not so open that your brains fall out.”
`Òphthalmology 518
—Arthur Hays Sulzberger
“The chief function of the body is to carry the brain around.” ``Pharmacology 528
—Thomas Edison
“Exactly how [the brain] operates remains one of the biggest unsolved
mysteries, and it seems the more we probe its secrets, the more surprises we
find.”
—Neil deGrasse Tyson
Know how to clinically interpret common patterns of neurologic

symptoms and findings. Questions on the exam often correlate clinical
scenarios with gross pathologic specimens or cross-sectional CT/MR
imaging. With regard to neuropharmacology, antiparkinsonism,
antiepileptic and opioid drugs tend to be highly testable.
473
FAS1_2018_12-Neurol_indexed_475-538.indd 473 10/12/17 11:23 AM

474 SEC TION III Neurology and Special Senses 
neurology—Embryology
NEUROLOGY—EMBRYOLOGY
``
Neural development Notochord induces overlying ectoderm to differentiate into neuroectoderm and form neural plate.
Neural plate Neural plate gives rise to neural tube and neural crest cells.
Day 18 Notochord becomes nucleus pulposus of intervertebral disc in adults.
Notochord
Neural fold Alar plate (dorsal): sensory
Same orientation as spinal cord.
Basal plate (ventral): motor
Neural tube
Neural
crest
cells
Day 21
Regional specification Telencephalon is the 1st part. Diencephalon is the 2nd part. The rest are arranged alphabetically:
of developing brain mesencephalon, metencephalon, myelencephalon.
Three primary Five secondary Adult derivatives of:
vesicles vesicles Walls Cavities
Telencephalon Cerebral Lateral

Wall Cavity hemispheres ventricles
Forebrain Diencephalon Thalamus, Third

(prosencephalon) Hypothalamus ventricle
Midbrain Mesencephalon Midbrain Cerebral

(mesencephalon) aqueduct
Pons Upper part of

fourth ventricle
Metencephalon
Hindbrain Cerebellum
(rhombencephalon)
Myelencephalon
Medulla Lower part of
fourth ventricle
Spinal cord
Central and peripheral Neuroepithelia in neural tube—CNS neurons, ependymal cells (inner lining of ventricles, make
nervous systems CSF), oligodendrocytes, astrocytes.
origins Neural crest—PNS neurons, Schwann cells.
Mesoderm—Microglia (like Macrophages).

Neurology and Special Senses 
neurology—Embryology SEC TION III 475
Neural tube defects Neuropores fail to fuse (4th week) persistent connection between amniotic cavity and spinal
canal. Associated with maternal diabetes as well as low folic acid intake before conception and
during pregnancy. α-fetoprotein (AFP) in amniotic fluid and maternal serum (except spina
bifida occulta = normal AFP). acetylcholinesterase (AChE) in amniotic fluid is a helpful
confirmatory test.
Spina bifida occulta Failure of caudal neuropore to close, but no herniation. Usually seen at lower vertebral levels. Dura
is intact. Associated with tuft of hair or skin dimple at level of bony defect.
Meningocele Meninges (but no neural tissue) herniate through bony defect. Associated with spina bifida cystica.
Meningomyelocele Meninges and neural tissue (eg, cauda equina) herniate through bony defect.
Myeloschisis Also known as rachischisis. Exposed unfused neural tissue without skin/meningeal covering.
Anencephaly Failure of rostral neuropore to close no forebrain, open calvarium. Clinical findings:
polyhydramnios (no swallowing center in brain).
+/− Tuft of hair Skin defect/thinning Skin thin or absent
Skin +/− Skin dimple
Subarachnoid
space
Dura
Leptomeninges
Spinal Transverse
cord process
Normal Spina bifida occulta Meningocele Meningomyelocele

(most common)
Holoprosencephaly Failure of left and right hemispheres to separate; usually occurs during weeks 5–6. May be related
A
to mutations in sonic hedgehog signaling pathway. Moderate form has cleft lip/palate, most severe
form results in cyclopia. Seen in trisomy 13 and fetal alcohol syndrome.
★ MRI A reveals monoventricle and fusion of basal ganglia (star in A ).

neurology—Embryology
Posterior fossa malformations

Chiari I malformation Ectopia of cerebellar tonsils (1 structure) A . Congenital, usually asymptomatic in childhood,
manifests in adulthood with headaches and cerebellar symptoms. Associated with spinal
cavitations (eg, syringomyelia).
Chiari II malformation Herniation of low-lying cerebellar vermis and tonsils (2 structures) through foramen magnum with
aqueductal stenosis hydrocephalus. Usually associated with lumbosacral meningomyelocele
(may present as paralysis/sensory loss at and below the level of the lesion).
Dandy-Walker Agenesis of cerebellar vermis leads to cystic enlargement of 4th ventricle (arrow in B ) that fills the
syndrome enlarged posterior fossa. Associated with noncommunicating hydrocephalus, spina bifida.
A B
Chiari I
malformation
Cbm
Syrinx Cbm
Syringomyelia Cystic cavity (syrinx) within central canal Syrinx = tube, as in syringe.
A
of spinal cord (yellow arrows in A ). Fibers Most common at C8–T1.
crossing in anterior white commissure
(spinothalamic tract) are typically damaged
first. Results in a “cape-like,” bilateral
symmetrical loss of pain and temperature
sensation in upper extremities (fine touch
sensation is preserved). Associated with Chiari
malformations (red arrow shows low-lying
cerebellar tonsils in A ) and other congenital
malformations; acquired causes include
trauma and tumors.

neurology—Anatomy and Physiology SEC TION III 477
Tongue development 1st and 2nd branchial arches form anterior 2/3 Taste—CN VII, IX, X (solitary nucleus).
(thus sensation via CN V3, taste via CN VII). Pain—CN V3, IX, X.
Taste Sensation
CN X CN X 3rd and 4th branchial arches form posterior 1/3 Motor—CN X, XII.
Arches
(thus sensation and taste mainly via CN IX,
CN IX
3 and 4
CN IX
extreme posterior via CN X).
Foramen
Sulcus Motor innervation is via CN XII to hyoglossus The Genie sticks out his tongue.
terminalis
caecum
(retracts and depresses tongue), genioglossus
Vallate
Arches papillae (protrudes tongue), and styloglossus (draws
1 and 2
sides of tongue upward to create a trough for
CN VII CN V₃
swallowing).
Motor innervation is via CN X to palatoglossus
(elevates posterior tongue during swallowing).
NEUROLOGY—ANATOMY AND PHYSIOLOGY

``
Neurons Signal-transmitting cells of the nervous system. Permanent cells—do not divide in adulthood.
Signal-relaying cells with dendrites (receive input), cell bodies, and axons (send output). Cell bodies
and dendrites can be seen on Nissl staining (stains RER). RER is not present in the axon.
Injury to axon Wallerian degeneration—degeneration of axon distal to site of injury and axonal
retraction proximally; allows for potential regeneration of axon (if in PNS). Macrophages remove
debris and myelin.
Astrocytes Most common glial cell type in CNS. Physical Derived from neuroectoderm. Astrocyte marker:
support, repair, extracellular K+ buffer, removal GFAP.
of excess neurotransmitter, component of
blood-brain barrier, glycogen fuel reserve
buffer. Reactive gliosis in response to neural
injury.
Microglia Phagocytic scavenger cells of CNS HIV-infected microglia fuse to form

(mesodermal, mononuclear origin). Activated multinucleated giant cells in CNS.
in response to tissue damage. Not readily
discernible by Nissl stain.
Ependymal cells Glial cells with a ciliated simple columnar form that line the ventricles and central canal of spinal
cord. Apical surfaces are covered in cilia (which circulate CSF) and microvilli (which help in CSF
absorption).

neurology—Anatomy and Physiology
Myelin conduction velocity of signals transmitted Wraps and insulates axons (arrow in A ): space
A down axons saltatory conduction of action constant and conduction velocity.
potential at the nodes of Ranvier, where there COPS: CNS = Oligodendrocytes, PNS =
are high concentrations of Na+ channels. Schwann cells.
Synthesis of myelin by oligodendrocytes in
CNS (including CN I and II) and Schwann
cells in PNS (including CN III-XII).
Schwann cells Each Schwann cell myelinates only 1 PNS axon. Injured in Guillain-Barré syndrome.
Nucleus Schwann cell
Also promote axonal regeneration. Derived
from neural crest.
Myelin sheath Node of Ranvier
Oligodendrocytes Myelinates axons of neurons in CNS. Each Derived from neuroectoderm.

Node of Ranvier oligodendrocyte can myelinate many axons “Fried egg” appearance histologically.
(∼ 30). Predominant type of glial cell in white Injured in multiple sclerosis, progressive
Axon matter. multifocal leukoencephalopathy (PML),
leukodystrophies.
Oligodendrocyte
Sensory receptors
RECEPTOR TYPE SENSORY NEURON FIBER TYPE LOCATION SENSES
Free nerve endings C—slow, unmyelinated fibers All skin, epidermis, some Pain, temperature
Aδ—fAst, myelinated fibers viscera
Meissner corpuscles Large, myelinated fibers; adapt Glabrous (hairless) skin Dynamic, fine/light touch,
quickly position sense
Pacinian corpuscles Large, myelinated fibers; adapt Deep skin layers, ligaments, Vibration, pressure
quickly joints
Merkel discs Large, myelinated fibers; adapt Finger tips, superficial skin Pressure, deep static touch (eg,
slowly shapes, edges), position sense
Ruffini corpuscles Dendritic endings with Finger tips, joints Pressure, slippage of objects
capsule; adapt slowly along surface of skin, joint
angle change

Peripheral nerve Endoneurium—invests single nerve fiber layers Endo = inner.

Nerve trunk (inflammatory infiltrate in Guillain-Barré Peri = around.
Epineurium
syndrome). Epi = outer.
Perineurium
Perineurium (blood-nerve Permeability
barrier)—surrounds a fascicle of nerve fibers.
Endoneurium
Must be rejoined in microsurgery for limb
Nerve fiber
reattachment.
Epineurium—dense connective tissue that
surrounds entire nerve (fascicles and blood
vessels).
Chromatolysis Reaction of neuronal cell body to axonal injury. Changes reflect protein synthesis in effort to
A repair the damaged axon. Characterized by:
Round cellular swelling A
Displacement of the nucleus to the periphery
Dispersion of Nissl substance throughout cytoplasm
Concurrent with Wallerian degeneration.
Neurotransmitter changes with disease

LOCATION OF ANXIETY DEPRESSION SCHIZOPHRENIA ALZHEIMER HUNTINGTON PARKINSON
SYNTHESIS DISEASE DISEASE DISEASE
Acetylcholine Basal nucleus
of Meynert
Dopamine Ventral
tegmentum,
SNc
GABA Nucleus
accumbens
Norepinephrine Locus ceruleus
Serotonin Raphe nucleus
Meninges Three membranes that surround and protect the CSF flows in the subarachnoid space, located
atte
teerr
Dura mater Sagittal
g sinus brain and spinal cord: between arachnoid and pia mater.
Bridging veins
ve
ein
ein
ns
s
Dura mater—thick outer layer closest to Epidural space—a potential space between the
Arachnoid
Arra
achn
ac noi
od
mater
ma
ma atte
er skull. Derived from mesoderm. dura mater and skull containing fat and blood
Pia
P ia mma
mater
atte
a err
Brain
Brra
ain
a n Arachnoid mater—middle layer, contains vessels.
web-like connections. Derived from neural
crest.
Pia mater—thin, fibrous inner layer that
firmly adheres to brain and spinal cord.
Derived from neural crest.

Blood-brain barrier Prevents circulating blood substances A few specialized brain regions with fenestrated
Astrocyte foot (eg, bacteria, drugs) from reaching the CSF/ capillaries and no blood-brain barrier allow
processes
CNS. Formed by 3 structures: molecules in blood to affect brain function (eg,
Capillary
Tight junctions between nonfenestrated area postrema—vomiting after chemo; OVLT
lumen capillary endothelial cells [organum vasculosum lamina terminalis]—
Tight
junction Basement Basement membrane osmotic sensing) or neurosecretory products to
membrane
Astrocyte foot processes enter circulation (eg, neurohypophysis—ADH
Glucose and amino acids cross slowly by carrier- release).
mediated transport mechanisms. Infarction and/or neoplasm destroys endothelial
Nonpolar/lipid-soluble substances cross rapidly cell tight junctions vasogenic edema.
via diffusion. Other notable barriers include:
Blood-testis barrier
Maternal-fetal blood barrier of placenta
Hypothalamus Maintains homeostasis by regulating Thirst and water balance, controlling Adenohypophysis
(anterior pituitary) and Neurohypophysis (posterior pituitary) release of hormones produced in
the hypothalamus, and regulating Hunger, Autonomic nervous system, Temperature, and Sexual
urges (TAN HATS).
Inputs (areas not protected by blood-brain barrier): OVLT (senses change in osmolarity), area
postrema (found in medulla, responds to emetics).
Lateral nucleus Hunger. Destruction anorexia, failure Lateral injury makes you Lean.
to thrive (infants). Stimulated by ghrelin,
inhibited by leptin.
Ventromedial nucleus Satiety. Destruction (eg, craniopharyngioma) VentroMedial injury makes you Very Massive.
hyperphagia. Stimulated by leptin.
Anterior nucleus Cooling, parasympathetic. Anterior nucleus = cool off (cooling,
pArasympathetic). A/C = anterior cooling.
Posterior nucleus Heating, sympathetic. Heating controlled by Posterior hypothalamus
(“Hot Pot”). If you zap your posterior
hypothalamus, you become a poikilotherm
(cold-blooded, like a snake).
Suprachiasmatic Circadian rhythm. You need sleep to be charismatic (chiasmatic).
nucleus
Supraoptic and Synthesize ADH and oxytocin. ADH and oxytocin are carried by neurophysins
paraventricular down axons to posterior pituitary, where these
nuclei hormones are stored and released.
Preoptic nucleus Thermoregulation, sexual behavior. Releases
GnRH. Failure of GnRH-producing neurons
to migrate from olfactory pit Kallmann
syndrome.

Vomiting center Coordinated by nucleus tractus solitarius (NTS) in the medulla, which receives information from
the chemoreceptor trigger zone (CTZ, located within area postrema in 4th ventricle), GI tract (via
vagus nerve), vestibular system, and CNS.
CTZ and adjacent vomiting center nuclei receive input from 5 major receptors: muscarinic (M1),
dopamine (D2), histamine (H1), serotonin (5-HT3), and neurokinin (NK-1) receptors.
5-HT3, D2, and NK-1 antagonists used to treat chemotherapy-induced vomiting.
M1 and H1 antagonists used to treat motion sickness and hyperemesis gravidarum.
Sleep physiology Sleep cycle is regulated by the circadian rhythm, which is driven by suprachiasmatic nucleus (SCN)
of hypothalamus. Circadian rhythm controls nocturnal release of ACTH, prolactin, melatonin,
norepinephrine: SCN norepinephrine release pineal gland melatonin. SCN is regulated
by environment (eg, light).
Two stages: rapid-eye movement (REM) and non-REM.
Alcohol, benzodiazepines, and barbiturates are associated with REM sleep and delta wave sleep;
norepinephrine also REM sleep.
Benzodiazepines are useful for night terrors and sleepwalking by N3 and REM sleep.
SLEEP STAGE (% OF TOTAL SLEEP DESCRIPTION EEG WAVEFORM
TIME IN YOUNG ADULTS)
Awake (eyes open) Alert, active mental concentration. Beta (highest frequency, lowest amplitude)
Awake (eyes closed) Alpha
Non-REM sleep
Stage N1 (5%) Light sleep. Theta
Stage N2 (45%) Deeper sleep; when bruxism (teeth grinding) Sleep spindles and K complexes
occurs. “Twoth” grinding
Stage N3 (25%) Deepest non-REM sleep (slow-wave sleep); Delta (lowest frequency, highest amplitude)
when sleepwalking, night terrors, and
bedwetting occur.
REM sleep (25%) Loss of motor tone, brain O2 use, and Beta
variable pulse and blood pressure ACh; At night, BATS Drink Blood
when dreaming, nightmares, and penile/
clitoral tumescence occur; may serve memory
processing function. Depression increases total
REM sleep but decreases REM latency.
Extraocular movements due to activity of PPRF
(paramedian pontine reticular formation/
conjugate gaze center).
Occurs every 90 minutes, and duration
through the night.

Thalamus Major relay for all ascending sensory information except olfaction.
NUCLEI INPUT SENSES DESTINATION MNEMONIC
Ventral Spinothalamic and dorsal columns/ Vibration, Pain, 1° somatosensory
Postero medial lemniscus Pressure, cortex
Lateral Proprioception,
nucleus Light touch,
temperature
Ventral Trigeminal and gustatory pathway Face sensation, 1° somatosensory Makeup goes on
postero taste cortex the face
Medial
nucleus
Lateral CN II, optic chiasm, optic tract Vision Calcarine sulcus Lateral = Light
geniculate
nucleus
Medial Superior olive and inferior colliculus of Hearing Auditory cortex of Medial = Music
geniculate tectum temporal lobe
nucleus
Ventral lateral Basal ganglia, cerebellum Motor Motor cortex
nucleus
Limbic system Collection of neural structures involved in The famous 5 F’s.

A
emotion, long-term memory, olfaction,
behavior modulation, ANS function.
Consists of hippocampus (red arrows
in A ), amygdalae, mammillary bodies, anterior
thalamic nuclei, cingulate gyrus (yellow arrows
in A ), entorhinal cortex. Responsible for
Feeding, Fleeing, Fighting, Feeling, and Sex.
Dopaminergic Commonly altered by drugs (eg, antipsychotics) and movement disorders (eg, Parkinson disease).
pathways
PATHWAY SYMPTOMS OF ALTERED ACTIVITY NOTES
Mesocortical activity “negative” symptoms (eg, anergia, Antipsychotic drugs have limited effect.
apathy, lack of spontaneity).
Mesolimbic activity “positive” symptoms (eg, delusions, 1° therapeutic target of antipsychotic drugs
hallucinations). positive symptoms (eg, in schizophrenia).
Nigrostriatal activity extrapyramidal symptoms Major dopaminergic pathway in brain.
(eg, dystonia, akathisia, parkinsonism, tardive Significantly affected by movement disorders
dyskinesia). and antipsychotic drugs.
Tuberoinfundibular activity prolactin libido, sexual
dysfunction, galactorrhea, gynecomastia (in
men).

Cerebellum Modulates movement; aids in coordination and Lateral lesions—affect voluntary movement of
A
balance. Arrow in A . extremities (lateral structures); when injured,
Input: propensity to fall toward injured (ipsilateral)
Contralateral cortex via middle cerebellar side.
peduncle. Medial lesions (eg, vermis, fastigial nuclei,
Ipsilateral proprioceptive information via flocculonodular lobe)—truncal ataxia (wide-
inferior cerebellar peduncle from spinal based cerebellar gait), nystagmus, head tilting.
cord. Generally result in bilateral motor deficits
Output: affecting axial and proximal limb musculature
The only output of cerebellar cortex = (medial structures).
Purkinje cells (always inhibitory) deep
nuclei of cerebellum contralateral cortex
via superior cerebellar peduncle.
Deep nuclei (lateral medial)—Dentate, Don’t Eat Greasy Foods
Emboliform, Globose, Fastigial.

Basal ganglia Important in voluntary movements and making postural D1-Receptor = D1Rect
adjustments. pathway.
Receives cortical input, provides negative feedback to cortex to Indirect (D2) = Inhibitory.
modulate movement.
Striatum = putamen (motor) + caudate (cognitive).
Lentiform = putamen + globus pallidus.
Input from SNc
Dopamine
D1 D2
Frontal plane
through brain
Direct Indirect Posterior Anterior
Motor cortex pathway pathway
facilitates inhibits
movement movement Lateral ventricle
Caudate nucleus
Thalamus
Internal capsule
From Striatum Subthalamic
Thalamus SNc nucleus (STN)
Lentiform Putamen
nucleus Globus pallidus Substantia
t
rec (GPe/GPi) nigra (SNc)
Di
ect
Indir
GPi GPe
STN
Pedunculo-
pontine
nucleus
Stimulatory
Spinal
cord Inhibitory
Direct (excitatory) pathway—SNc input stimulates the striatum, stimulating the release of GABA,
which inhibits GABA release from the GPi, disinhibiting the thalamus via the GPi ( motion).
Indirect (inhibitory) pathway—SNc input stimulates the striatum, releasing GABA that disinhibits
STN via GPe inhibition, and STN stimulates GPi to inhibit the thalamus ( motion).
Dopamine binds to D1, stimulating the excitatory pathway, and to D2, inhibiting the inhibitory
pathway motion.

Cerebral cortex regions
Premotor Central sulcus Somatosensory

cortex association cortex
ry
Frontal eye
so
to
a to a ry
se n
Parietal
mo
field Frontal
somP rim
ar y
lobe lobe
P rim
Prefrontal
association area iculus
fasc
cuate
Ar
Broca area Wernicke area

Occipital
Temporal lobe
lobe Primary
Sylvian fissure visual cortex
Limbic Primary
association area auditory cortex
Homunculus Topographic representation of motor (shown)

and sensory areas in the cerebral cortex.
Distorted appearance is due to certain body
Shouk
Trun
regions being more richly innervated and thus

Elbower
Wris
Hipnee
Hand
K nkle
t
ld
A
having cortical representation.

le
Litt
Mid Ring
Th Ind led
N um x
e
Toe
Bro eck b
s
all
rs
eb e
ge
ey Fac
Fin
nd
d a Lips
eli
Vocalization
Ey
Jaw
Salivation
Mastication
Tongue
Swallowing
Medial Lateral

Cerebral perfusion Brain perfusion relies on tight autoregulation. Therapeutic hyperventilation Pco2
Cerebral perfusion is primarily driven by vasoconstriction cerebral blood flow
Pco2 (Po2 also modulates perfusion in severe intracranial pressure (ICP). May be used
hypoxia). to treat acute cerebral edema (eg, 2° to stroke)
Cerebral perfusion relies on a pressure gradient unresponsive to other interventions.
between mean arterial pressure (MAP) and CPP = MAP – ICP. If CPP = 0, there is no
ICP. blood pressure or ICP cerebral cerebral perfusion brain death.
perfusion pressure (CPP). Hypoxemia increases CPP only if Po2
< 50 mm Hg.
CPP is directly proportional to Pco2 until Pco2
> 90 mm Hg.
100
PaCO₂
PaO₂
Cerebral blood flow (mL/100g/min) MAP
75
50
25
0
0 50 100 150 200
Pressure (mm Hg)
Cerebral arteries—cortical distribution
Anterior cerebral artery (supplies anteromedial surface)
Middle cerebral artery (supplies lateral surface)

Anterior
Posterior cerebral artery (supplies posterior and inferior surfaces)
Anterior
Posterior
Posterior
Watershed zones Between anterior cerebral/middle cerebral, Damage by severe hypotension proximal upper
A
posterior cerebral/middle cerebral arteries and lower extremity weakness (if internal border
(cortical border zones) (blue areas in A ); or may zone stroke), higher order visual dysfunction
also occur between the superficial and deep (if posterior cerebral/middle cerebral cortical
vascular territories of the middle cerebral artery border zone stroke).
(internal border zones) (red areas in A ).

Circle of Willis System of anastomoses between anterior and posterior blood supplies to brain.
ACom Anterior
communicating Optic chiasm
A2
Anterior
ACA
cerebral A1 Internal carotid ICA
ACA
Anterior
circulation Middle MCA
MCA Lenticulo-
cerebral striate
ACA PCA
ICA M1
OF
MCA Posterior
PCom Anterior
Posterior communicating choroidal BA
circulation P1
P2 PCom
Posterior
PCA
cerebral ICA
ECA
CCA
VA
Superior
SCA Pontine
cerebellar Brachio-
cephalic
Sub-
clavian
Anterior inferior
AICA Basilar BA
cerebellar
Aorta
Posterior inferior Vertebral VA

PICA
cerebellar OBLIQUE-LATERAL VIEW
INFERIOR VIEW
Anterior spinal ASA
Dural venous sinuses Large venous channels A that run through the periosteal and meningeal layers of the dura mater.
A
Drain blood from cerebral veins (arrow) and receive CSF from arachnoid granulations. Empty
into internal jugular vein.
Venous sinus thrombosis—presents with signs/symptoms of ICP (eg, headache, seizures, focal
neurologic deficits). May lead to venous hemorrhage. Associated with hypercoagulable states (eg,
pregnancy, OCP use, factor V Leiden).
Superior sagittal sinus

(main location of CSF return
via arachnoid granulations)
Inferior sagittal sinus
Great cerebral vein of Galen Superior ophthalmic vein

Sphenoparietal sinus
Straight sinus
Cavernous sinus
Confluence of the sinuses
Sigmoid sinus
Occipital sinus
Jugular foramen
Transverse sinus
Internal jugular vein

Ventricular system Lateral ventricles 3rd ventricle via right and

Lateral ventricles left interventricular foramina of Monro.
Anterior Occipital 3rd ventricle 4th ventricle via cerebral
horn horn aqueduct of Sylvius.
4th ventricle subarachnoid space via:
Foramina of Luschka = Lateral.
Foramina
of Monro Foramen of Magendie = Medial.
Third Cerebral CSF made by ependymal cells of choroid
ventricle aqueduct plexus. Travels to subarachnoid space via
of Sylvius
foramina of Luschka and Magendie, is
Foramina of Luschka Fourth reabsorbed by arachnoid granulations, and
ventricle
then drains into dural venous sinuses.
Foramen of Magendie
Brain stem—ventral view 4 CN are above pons (I, II, III, IV).
Olfactory bulb
4 CN exit the pons (V, VI, VII, VIII).
Optic chiasm (CN I) 4 CN are in medulla (IX, X, XI, XII).
Olfactory tract 4 CN nuclei are medial (III, IV, VI, XII).
Infundibulum
CN II “Factors of 12, except 1 and 2.”
Optic tract
CN III
Mammillary body CN IV
(arises dorsally
and immediately
decussates)
Pons
CN V
Middle cerebellar CN VI
peduncle CN VII
CN VIII
Pyramid
CN IX
Pyramidal CN X
decussation CN XI
CN XII
C1
Brain stem—dorsal view (cerebellum removed) Pineal gland—melatonin secretion, circadian

rhythms.
3rd ventricle
Superior colliculi—direct eye movements
Thalamus to stimuli (noise/movements) or objects of
Superior colliculus
interest.
Inferior colliculi—auditory.
Inferior colliculus
Pineal gland Your eyes are above your ears, and the superior
Superior cerebellar colliculus (visual) is above the inferior
peduncle
colliculus (auditory).
Middle cerebellar
Anterior wall of peduncle
fourth ventricle
Inferior cerebellar
peduncle
Medulla

Cranial nerve nuclei Located in tegmentum portion of brain stem Lateral nuclei = sensory (aLar plate).
(between dorsal and ventral portions): —Sulcus limitans—
Midbrain—nuclei of CN III, IV Medial nuclei = Motor (basal plate).
Pons—nuclei of CN V, VI, VII, VIII
Medulla—nuclei of CN IX, X, XII
Spinal cord—nucleus of CN XI
Cranial nerve and vessel pathways
Anterior Cribriform plate CN I

cranial fossa
CN II
Optic canal Ophthalmic artery
CN III
Middle CN IV
cranial fossa Superior orbital fissure CN VI
(through
sphenoid bone)
CN V1
Foramen Rotundum CN V2
Foramen Ovale CN V3
Foramen spinosum Middle meningeal artery
Internal auditory meatus CN VII
CN VIII
Posterior CN IX
cranial fossa CN X
Jugular foramen CN XI
(through
temporal or Jugular vein
occipital bone) CN XII
Hypoglossal canal
Brain stem
Foramen magnum Spinal root of CN XI
Vertebral arteries
Divisions of CN V exit owing to Standing Room Only

Cranial nerves
NERVE CN FUNCTION TYPE MNEMONIC
Olfactory I Smell (only CN without thalamic relay to cortex) Sensory Some
Optic II Sight Sensory Say
Oculomotor III Eye movement (SR, IR, MR, IO), pupillary constriction Motor Marry
(sphincter pupillae: Edinger-Westphal nucleus, muscarinic
receptors), accommodation, eyelid opening (levator palpebrae)
Trochlear IV Eye movement (SO) Motor Money
Trigeminal V Mastication, facial sensation (ophthalmic, maxillary, mandibular Both But
divisions), somatosensation from anterior 2/3 of tongue
Abducens VI Eye movement (LR) Motor My
Facial VII Facial movement, taste from anterior of tongue (chorda tympani),
2/3 Both Brother
lacrimation, salivation (submandibular and sublingual glands are
innervated by CN seven), eyelid closing (orbicularis oculi), auditory
volume modulation (stapedius)
Vestibulocochlear VIII Hearing, balance Sensory Says
Glossopharyngeal IX Taste and sensation from posterior 1/3 of tongue, swallowing, Both Big
salivation (parotid gland), monitoring carotid body and sinus
chemo- and baroreceptors, and elevation of pharynx/larynx
(stylopharyngeus)
Vagus X Taste from supraglottic region, swallowing, soft palate elevation, Both Brains
midline uvula, talking, cough reflex, parasympathetics to
thoracoabdominal viscera, monitoring aortic arch chemo- and
baroreceptors
Accessory XI Head turning, shoulder shrugging (SCM, trapezius) Motor Matter
Hypoglossal XII Tongue movement Motor Most
Vagal nuclei
NUCLEUS FUNCTION CRANIAL NERVES
Nucleus Solitarius Visceral Sensory information (eg, taste, VII, IX, X
baroreceptors, gut distention)
Nucleus aMbiguus Motor innervation of pharynx, larynx, upper IX, X, XI (cranial portion)
esophagus (eg, swallowing, palate elevation)
Dorsal motor nucleus Sends autonomic (parasympathetic) fibers to X
heart, lungs, upper GI
Cranial nerve reflexes

REFLEX AFFERENT EFFERENT
Corneal V1 ophthalmic (nasociliary branch) Bilateral VII (temporal branch: orbicularis oculi)
Lacrimation V1 (loss of reflex does not preclude emotional VII
tears)
Jaw jerk V3 (sensory—muscle spindle from masseter) V3 (motor—masseter)
Pupillary II III
Gag IX X

Mastication muscles 3 muscles close jaw: Masseter, teMporalis, M’s Munch.

Medial pterygoid. 1 opens: Lateral pterygoid. Lateral Lowers (when speaking of pterygoids
All are innervated by trigeminal nerve (V3). with respect to jaw motion).
“It takes more muscle to keep your mouth shut.”
Spinal nerves There are 31 pairs of spinal nerves in total: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal.
Nerves C1–C7 exit above the corresponding vertebra. C8 spinal nerve exits below C7 and above
T1. All other nerves exit below (eg, C3 exits above the 3rd cervical vertebra; L2 exits below the
2nd lumbar vertebra).
Vertebral disc herniation—nucleus pulposus (soft central disc) herniates through annulus fibrosus
(outer ring); usually occurs posterolaterally at L4–L5 or L5–S1. Nerve usually affected is below
the level of herniation (eg, L3–L4 disc spares L3 nerve and involves L4 nerve). Compression of S1
nerve root absent ankle reflex.
Spinal cord—lower In adults, spinal cord ends at lower border of Goal of lumbar puncture is to obtain sample of
extent L1–L2 vertebrae. Subarachnoid space (which CSF without damaging spinal cord. To keep
contains the CSF) extends to lower border the cord alive, keep the spinal needle between
of S2 vertebra. Lumbar puncture is usually L3 and L5.
performed between L3–L4 or L4–L5 (level of
cauda equina).

Spinal cord and Legs (Lumbosacral) are Lateral in Lateral corticospinal, spinothalamic tracts A .
associated tracts Dorsal columns are organized as you are, with hands at sides. “Arms outside, legs inside.”
A Central canal
Dorsal column
Posterior horn
Anterior white commissure Lateral

corticospinal tract
Anterior spinothalamic tract

Anterior horn
ASCENDING
Dorsal column
(pressure, vibration, fine touch, proprioception)
Central canal
• Fasciculus graciLis (Lower body, legs)
• Fasciculus cUneatus (Upper body, arms)
Posterior horn
Lumbar
Sacral
acic
l
vica
DESCENDING
Thor
Gray matter
Cer
Lateral corticospinal tract Intermediate horn (sympathetic)

(voluntary motor) (T1 - L2/L3)
• Sacral
• Cervical
ASCENDING
Anterior corticospinal tract
(voluntary motor) Lateral spinothalamic tract (pain, temperature)
• Sacral
White matter • Cervical
Anterior spinothalamic tract (crude touch, pressure)
Anterior horn

Spinal tract anatomy Ascending tracts synapse and then cross.

and functions
TRACT FUNCTION 1ST-ORDER NEURON SYNAPSE 1 2ND-ORDER NEURON SYNAPSE 2 + PROJECTIONS
Ascending tracts
Dorsal column Pressure, Sensory nerve Nucleus Decussates
vibration, ending bypass gracilis, in medulla
fine touch, pseudounipolar cell nucleus ascends
proprioception body in dorsal root cuneatus contralaterally
ganglion enter (ipsilateral as the medial
spinal cord ascend medulla) lemniscus
ipsilaterally in dorsal
columns VPL (thalamus)
sensory cortex
Spinothalamic tract Lateral: pain, Sensory nerve Ipsilateral gray Decussates
temperature ending (Aδ and C matter (spinal in spinal
Anterior: fibers) bypass cord) cord as the
crude touch, pseudounipolar cell anterior white
pressure body in dorsal root commissure
ganglion enter ascends
spinal cord contralaterally
Descending tract
Lateral corticospinal Voluntary UMN: cell body in Cell body of LMN: leaves NMJ muscle
tract movement of 1° motor cortex anterior horn spinal cord fibers
contralateral descends ipsilaterally (spinal cord)
limbs (through posterior
limb of internal
capsule), most fibers
decussate at caudal
medulla (pyramidal
decussation)
descends
contralaterally

Clinical reflexes Reflexes count up in order (main nerve root Additional reflexes:
bolded): Cremasteric reflex = L1, L2 (“testicles move”)
Achilles reflex = S1, S2 (“buckle my shoe”) Anal wink reflex = S3, S4 (“winks galore”)
C5, 6 Patellar reflex = L3, L4 (“kick the door”)
C7, 8 Biceps and brachioradialis reflexes = C5,
C6 (“pick up sticks”)
L3, 4
Triceps reflex = C7, C8 (“lay them straight”)
S1, 2
Primitive reflexes CNS reflexes that are present in a healthy infant, but are absent in a neurologically intact adult.
Normally disappear within 1st year of life. These “primitive” reflexes are inhibited by a mature/
developing frontal lobe. They may reemerge in adults following frontal lobe lesions loss of
inhibition of these reflexes.
Moro reflex “Hang on for life” reflex—abduct/extend arms when startled, and then draw together
Rooting reflex Movement of head toward one side if cheek or mouth is stroked (nipple seeking)
Sucking reflex Sucking response when roof of mouth is touched
Palmar reflex Curling of fingers if palm is stroked
Plantar reflex Dorsiflexion of large toe and fanning of other toes with plantar stimulation
Babinski sign—presence of this reflex in an adult, which may signify a UMN lesion
Galant reflex Stroking along one side of the spine while newborn is in ventral suspension (face down) causes
lateral flexion of lower body toward stimulated side
Landmark dermatomes
DERMATOME CHARACTERISTICS
C2 Posterior half of skull
C3 High turtleneck shirt
V1
C2
C3
Diaphragm and gallbladder pain referred to the V2

V3
C2 C4
C5
C6
C3
right shoulder via phrenic nerve

C7
C4 C8
C5 T1
T1 T2
C3, 4, 5 keeps the diaphragm alive

T3
T2 T4
T3 T5
T4 T6
T7
C4 Low-collar shirt
T5 T8
T6 C6 T9
T7 C6 C8 T10
T11
T8 C7 T12
C6 Includes thumbs
T9 L1
C5 L2
T10 L3
L4
Thumbs up sign on left hand looks like a 6

T11 L5
T12 L1 S1
S2 S3
C6 S4
S5
At the nipple
L2
T4
C7
C8 C8
S2 S3
L3
T4 at the teat pore

L5 S1 S2
L4 L1
T7 At the xiphoid process L2
T10 At the umbilicus (belly butten) L3
Important point of referred pain in early L5 S1 S2
appendicitis L4
S1 S1
L1 At the Inguinal Ligament L4

L5
L4 Includes the kneecaps

L5
L4
Down on ALL 4’s

S2, S3, S4 Sensation of penile and anal zones
S2, 3, 4 keep the penis off the floor

neurology—Neuropathology SEC TION III 495
NEUROLOGY—NEUROPATHOLOGY
``
Common brain lesions

AREA OF LESION CONSEQUENCE EXAMPLES/COMMENTS
Frontal lobe Disinhibition and deficits in concentration,
orientation, judgment; may have reemergence
of primitive reflexes.
Frontal eye fields Eyes look toward (destructive) side of lesion. In
seizures (irritative), eyes look away from side of
the lesion.
Paramedian pontine Eyes look away from side of lesion. Ipsilateral gaze palsy (inability to look toward
reticular formation side of lesion).
Medial longitudinal Internuclear ophthalmoplegia (impaired Multiple sclerosis.
fasciculus adduction of ipsilateral eye; nystagmus of
contralateral eye with abduction).
Dominant parietal Agraphia, acalculia, finger agnosia, left-right Gerstmann syndrome.
cortex disorientation.
Nondominant parietal Agnosia of the contralateral side of the world. Hemispatial neglect syndrome.
cortex
Hippocampus Anterograde amnesia—inability to make new
(bilateral) memories.
Basal ganglia May result in tremor at rest, chorea, athetosis. Parkinson disease, Huntington disease.
Subthalamic nucleus Contralateral hemiballismus.
Mammillary bodies Wernicke-Korsakoff syndrome—Confusion, Wernicke problems come in a CAN O’ beer.
(bilateral) Ataxia, Nystagmus, Ophthalmoplegia,
memory loss (anterograde and retrograde
amnesia), confabulation, personality changes.
Amygdala (bilateral) Klüver-Bucy syndrome—disinhibited behavior HSV-1 encephalitis.
(eg, hyperphagia, hypersexuality, hyperorality).
Dorsal midbrain Parinaud syndrome—vertical gaze palsy, Stroke, hydrocephalus, pinealoma.
pupillary light-near dissociation, lid retraction,
convergence-retraction nystagmus.
Reticular activating Reduced levels of arousal and wakefulness
system (midbrain) (eg, coma).
Cerebellar hemisphere Intention tremor, limb ataxia, loss of balance; Cerebellar hemispheres are laterally located—
damage to cerebellum ipsilateral deficits; affect lateral limbs.
fall toward side of lesion.
Red nucleus Decorticate (flexor) posturing—lesion above Worse prognosis with decerebrate posturing.
red nucleus, presents with flexion of upper
extremities and extension of lower extremities.
Decerebrate (extensor) posturing—lesion at or
below red nucleus, presents with extension of
upper and lower extremities.
Cerebellar vermis Truncal ataxia (wide-based, “drunken sailor” Vermis is centrally located—affects central body.
gait), dysarthria. Degeneration associated with chronic alcohol
use.

neurology—Neuropathology
Ischemic brain Irreversible damage begins after 5 minutes of hypoxia. Most vulnerable: hippocampus, neocortex,
disease/stroke cerebellum (Purkinje cells), watershed areas. Irreversible neuronal injury. Hippocampus is most
vulnerable to ischemic hypoxia (“vulnerable hippos”).
Stroke imaging: noncontrast CT to exclude hemorrhage (before tPA can be given). CT detects
ischemic changes in 6–24 hr. Diffusion-weighted MRI can detect ischemia within 3–30 min.
TIME SINCE ISCHEMIC 12–24 HOURS 24–72 HOURS 3–5 DAYS 1–2 WEEKS > 2 WEEKS
EVENT
Histologic Eosinophilic Necrosis + Macrophages Reactive gliosis Glial scar
features cytoplasm neutrophils (microglia) (astrocytes)
+ pyknotic + vascular
nuclei (red proliferation
neurons)
Ischemic stroke Acute blockage of vessels disruption of blood flow and subsequent ischemia liquefactive
A necrosis.
3 types:
Thrombotic—due to a clot forming directly at site of infarction (commonly the MCA A ),
usually over an atherosclerotic plaque.
Embolic—embolus from another part of the body obstructs vessel. Can affect multiple vascular
territories. Examples: atrial fibrillation, carotid artery stenosis, DVT with patent foramen ovale.
Hypoxic—due to hypoperfusion or hypoxemia. Common during cardiovascular surgeries, tends
to affect watershed areas.
Treatment: tPA (if within 3–4.5 hr of onset and no hemorrhage/risk of hemorrhage). Reduce risk
with medical therapy (eg, aspirin, clopidogrel); optimum control of blood pressure, blood sugars,
lipids; and treat conditions that risk (eg, atrial fibrillation, carotid artery stenosis).
Transient ischemic Brief, reversible episode of focal neurologic dysfunction without acute infarction (⊝ MRI), with the
attack majority resolving in < 15 minutes; deficits due to focal ischemia.
Neonatal Bleeding into ventricles (arrow in A shows blood in right intraventricular blood, extending into
intraventricular periventricular white matter). Increased risk in premature and low-birth-weight infants. Originates
hemorrhage in germinal matrix, a highly vascularized layer within the subventricular zone. Due to reduced
A
glial fiber support and impaired autoregulation of BP in premature infants. Can present with
altered level of consciousness, bulging fontanelle, hypotension, seizures, coma.

Intracranial hemorrhage
Epidural hematoma Rupture of middle meningeal artery (branch A B
of maxillary artery), often 2° to skull fracture
(circle in A ) involving the pterion (thinnest
area of the lateral skull). Lucid interval.
Scalp hematoma (arrows in A ) and rapid
intracranial expansion (arrows in B ) under
systemic arterial pressure transtentorial
herniation, CN III palsy.
CT shows biconvex (lentiform), hyperdense
blood collection B not crossing suture lines.
Subdural hematoma Rupture of bridging veins. Can be acute C D
(traumatic, high-energy impact hyperdense
on CT) or chronic (associated with mild
trauma, cerebral atrophy, elderly, alcoholism
hypodense on CT). Also seen in shaken
babies. Predisposing factors: brain atrophy,
trauma.
Crescent-shaped hemorrhage (red arrows in C
and D ) that crosses suture lines. Can cause
midline shift (yellow arrow in C ), findings of
“acute on chronic” hemorrhage (blue arrows
in D ).
Subarachnoid Bleeding E F due to trauma, or rupture of an E F
hemorrhage aneurysm (such as a saccular aneurysm E )
or arteriovenous malformation. Rapid time
course. Patients complain of “worst headache
of my life.” Bloody or yellow (xanthochromic)
spinal tap. Vasospasm can occur due to
blood breakdown or rebleed 3–10 days after
hemorrhage ischemic infarct; nimodipine
used to prevent/reduce vasospasm. risk of
developing communicating and/or obstructive
hydrocephalus.
Intraparenchymal Most commonly caused by systemic G H
hemorrhage hypertension. Also seen with amyloid
angiopathy (recurrent lobar hemorrhagic
stroke in elderly), vasculitis, neoplasm. May
be 2º to reperfusion injury in ischemic
stroke. Hypertensive hemorrhages (Charcot-
Bouchard microaneurysm) most often occur
in putamen of basal ganglia (lenticulostriate
vessels G ), followed by thalamus, pons, and
cerebellum H .

Effects of strokes
ARTERY AREA OF LESION SYMPTOMS NOTES
Anterior circulation
Middle Motor and sensory cortices A —upper Contralateral paralysis and sensory Wernicke aphasia is associated
cerebral limb and face. loss—face and upper limb. with right superior quadrant
artery Temporal lobe (Wernicke area); Aphasia if in dominant (usually visual field defect due to
frontal lobe (Broca area). left) hemisphere. Hemineglect temporal lobe involvement.
if lesion affects nondominant
(usually right) side.
Anterior Motor and sensory cortices—lower Contralateral paralysis and
cerebral limb. sensory loss—lower limb, urinary
artery incontinence.
Lenticulo Striatum, internal capsule. Contralateral paralysis. Absence Common location of lacunar
striate of cortical signs (eg, neglect, infarcts B , due to hyaline
artery aphasia, visual field loss). arteriosclerosis 2° to
unmanaged hypertension.
Posterior circulation
Anterior Lateral corticospinal tract. Contralateral paralysis—upper and Medial medullary syndrome—
spinal lower limbs. caused by infarct of
artery Medial lemniscus. contralateral proprioception. paramedian branches of ASA
Caudal medulla—hypoglossal nerve. Ipsilateral hypoglossal dysfunction and/or vertebral arteries.
(tongue deviates ipsilaterally).
Posterior Lateral medulla: Lateral medullary (Wallenberg)
inferior Nucleus ambiguus (CN IX, X, XI) Dysphagia, hoarseness, gag syndrome.
cerebellar reflex, hiccups Nucleus ambiguus effects are
artery Vestibular nuclei Vomiting, vertigo, nystagmus specific to PICA lesions C .
Lateral spinothalamic tract, spinal pain and temperature sensation “Don’t pick a (PICA) horse
trigeminal nucleus from contralateral body, (hoarseness) that can’t eat
ipsilateral face (dysphagia).”
Sympathetic fibers Ipsilateral Horner syndrome Also supplies inferior cerebellar
Inferior cerebellar peduncle Ipsilateral ataxia, dysmetria peduncle (part of cerebellum).
Anterior Lateral pons: Lateral pontine syndrome.
inferior Facial nucleus Paralysis of face (LMN lesion vs Facial nucleus effects are
cerebellar UMN lesion in cortical stroke), specific to AICA lesions.
artery lacrimation, salivation, taste “Facial droop means AICA’s
from anterior 2⁄3 of tongue pooped.”
Vestibular nuclei Vomiting, vertigo, nystagmus Also supplies middle and
Spinothalamic tract, spinal pain and temperature sensation inferior cerebellar peduncles
trigeminal nucleus from contralateral body, (part of cerebellum).
ipsilateral face
Sympathetic fibers Ipsilateral Horner syndrome
Middle and inferior cerebellar Ataxia, dysmetria
peduncles
Labyrinthine artery Ipsilateral sensorineural deafness,
vertigo

Effects of strokes (continued)

ARTERY AREA OF LESION SYMPTOMS NOTES
Basilar artery Pons, medulla, lower midbrain RAS spared, therefore preserved Locked-in syndrome (locked
consciousness in the basement)
Corticospinal and corticobulbar Quadriplegia; loss of voluntary
tracts facial, mouth, and tongue
movements
Ocular cranial nerve nuclei, Loss of horizontal, but not vertical,
paramedian pontine reticular eye movements
formation
Posterior Occipital lobe D . Contralateral hemianopia with
cerebral macular sparing; alexia without
artery agraphia (dominant hemisphere).
A B C D
Central post-stroke Neuropathic pain due to thalamic lesions. Initial paresthesias followed in weeks to months by
pain syndrome allodynia (ordinarily painless stimuli cause pain) and dysesthesia on the contralateral side. Occurs
in 10% of stroke patients.
Diffuse axonal injury Caused by traumatic shearing forces during rapid acceleration and/or deceleration of the brain (eg,
motor vehicle accident). Usually results in devastating neurologic injury, often causing coma or
A
persistent vegetative state. A shows multiple lesions (punctate hemorrhages) involving the white
matter tracts.

Aphasia Aphasia—higher-order language deficit (inability to understand/produce/use language appropriately);

caused by pathology in dominant cerebral hemisphere (usually left).
Dysarthria—motor inability to speak (movement deficit).
TYPE SPEECH FLUENCY COMPREHENSION COMMENTS
Repetition impaired
Broca (expressive) Nonfluent Intact Broca = Broken Boca (boca = mouth in Spanish).
Broca area in inferior frontal gyrus of frontal lobe. Patient
appears frustrated, insight intact.
Wernicke (receptive) Fluent Impaired Wernicke is Wordy but makes no sense. Patients do not
have insight.
Wernicke area in superior temporal gyrus of temporal
lobe.
Conduction Fluent Intact Can be caused by damage to arCuate fasciculus.
Global Nonfluent Impaired Arcuate fasciculus; Broca and Wernicke areas affected
(all areas).
Repetition intact
Transcortical motor Nonfluent Intact Affects frontal lobe around Broca area, but Broca area is
spared.
Transcortical sensory Fluent Impaired Affects temporal lobe around Wernicke area, but
Wernicke area is spared.
Transcortical, mixed Nonfluent Impaired Broca and Wernicke areas and arcuate fasciculus remain
intact; surrounding watershed areas affected.
Aneurysms Abnormal dilation of an artery due to weakening of vessel wall.

Saccular aneurysm Also known as berry aneurysm. Occurs at bifurcations in the circle of Willis. Most common site
is junction of ACom and ACA. Associated with ADPKD, Ehlers-Danlos syndrome. Other risk
factors: advanced age, hypertension, smoking, race ( risk in African-Americans).
Usually clinically silent until rupture (most common complication) subarachnoid hemorrhage
(“worst headache of my life” or “thunderclap headache”) focal neurologic deficits. Can also
cause symptoms via direct compression of surrounding structures by growing aneurysm.
ACom—compression bitemporal hemianopia (compression of optic chiasm); visual acuity
deficits; rupture ischemia in ACA distribution contralateral lower extremity hemiparesis,
sensory deficits.
MCA—rupture ischemia in MCA distribution contralateral upper extremity and lower
facial hemiparesis, sensory deficits.
PCom—compression ipsilateral CN III palsy mydriasis (“blown pupil”); may also see
ptosis, “down and out” eye.
Charcot-Bouchard Common, associated with chronic hypertension; affects small vessels (eg, lenticulostriate arteries in
microaneurysm basal ganglia, thalamus) and can cause lacunar strokes. Not visible on angiography.

Seizures Characterized by synchronized, high-frequency neuronal firing. Variety of forms.

Partial (focal) seizures Affect single area of the brain. Most commonly Epilepsy—a disorder of recurrent seizures
originate in medial temporal lobe. Types: (febrile seizures are not epilepsy).
Simple partial (consciousness intact)— Status epilepticus—continuous (≥ 5 min) or
motor, sensory, autonomic, psychic recurring seizures that may result in brain
Complex partial (impaired consciousness, injury.
automatisms) Causes of seizures by age:
Generalized seizures Diffuse. Types: Children—genetic, infection (febrile),
Absence (petit mal)—3 Hz spike-and-wave trauma, congenital, metabolic
discharges, no postictal confusion, blank Adults—tumor, trauma, stroke, infection
stare Elderly—stroke, tumor, trauma, metabolic,
Tonic phase
Myoclonic—quick, repetitive jerks infection
Tonic-clonic (grand mal)—alternating
Clonic phase stiffening and movement
Tonic—stiffening
Atonic—“drop” seizures (falls to floor);
commonly mistaken for fainting

Headaches Pain due to irritation of structures such as the dura, cranial nerves, or extracranial structures. More
common in females, except cluster headaches.
CLASSIFICATION LOCALIZATION DURATION DESCRIPTION TREATMENT
Clustera Unilateral 15 min–3 hr; Excruciating periorbital pain Acute: sumatriptan, 100% O2
repetitive (“suicide headache”) with Prophylaxis: verapamil
lacrimation and rhinorrhea.
May present with Horner
syndrome. More common in
males.
Tension Bilateral > 30 min Steady, “band-like” pain. No Analgesics, NSAIDs,
(typically 4–6 photophobia or phonophobia. acetaminophen;
hr); constant No aura. amitriptyline for chronic
pain
Migraine Unilateral 4–72 hr Pulsating pain with Acute: NSAIDs, triptans,
nausea, photophobia, or dihydroergotamine
phonophobia. May have Prophylaxis: lifestyle changes
“aura.” Due to irritation of (eg, sleep, exercise, diet),
CN V, meninges, or blood β-blockers, amitriptyline,
vessels (release of substance topiramate, valproate.
P, calcitonin gene-related POUND–Pulsatile, One-day
peptide, vasoactive peptides). duration, Unilateral, Nausea,
Disabling
Other causes of headache include subarachnoid hemorrhage (“worst headache of my life”), meningitis, hydrocephalus,
neoplasia, giant cell (temporal) arteritis.
a Compare with trigeminal neuralgia, which produces repetitive, unilateral, shooting pain in the distribution of CN V.
Triggered by chewing, talking, touching certain parts of the face. Lasts (typically) for seconds to minutes, but episodes often
increase in intensity and frequency over time. First-line therapy: carbamazepine.

Movement disorders
DISORDER PRESENTATION CHARACTERISTIC LESION NOTES
Akathisia Restlessness and intense urge Can be seen with neuroleptic
to move use or as a side-effect of
Parkinson treatment.
Asterixis Extension of wrists causes Associated with hepatic
“flapping” motion encephalopathy, Wilson
disease, and other metabolic
derangements.
Athetosis Slow, snake-like, writhing Basal ganglia
movements; especially seen in
the fingers
Chorea Sudden, jerky, purposeless Basal ganglia Chorea = dancing.
movements Seen in Huntington disease
and in acute rheumatic fever
(Sydenham chorea).
Dystonia Sustained, involuntary muscle Writer’s cramp, blepharospasm,
contractions torticollis.
Essential tremor High-frequency tremor Often familial. Patients often
with sustained posture self-medicate with alcohol,
(eg, outstretched arms), which tremor amplitude.
worsened with movement or Treatment: nonselective
when anxious β-blockers (eg, propranolol),
primidone.
Hemiballismus Sudden, wild flailing of 1 arm Contralateral subthalamic Pronounce “Half-of-body
+/− ipsilateral leg nucleus (eg, lacunar stroke) ballistic.”
Contralateral lesion.
Intention tremor Slow, zigzag motion when Cerebellar dysfunction
pointing/extending toward a
target
Myoclonus Sudden, brief, uncontrolled Jerks; hiccups; common in
muscle contraction metabolic abnormalities such
as renal and liver failure.
Resting tremor Uncontrolled movement of Substantia nigra (Parkinson Occurs at rest; “pill-rolling
distal appendages (most disease) tremor” of Parkinson disease.
noticeable in hands); tremor When you park your car, it is
alleviated by intentional at rest.
movement
Restless legs Worse at rest/nighttime. Associated with iron deficiency,
syndrome Relieved by movement CKD. Treat with dopamine
agonists (pramipexole,
ropinirole).

Neurodegenerative in cognitive ability, memory, or function with intact consciousness.

disorders Must rule out depression as cause of dementia (known as pseudodementia).
DISEASE DESCRIPTION HISTOLOGIC/GROSS FINDINGS
Parkinson disease Parkinson TRAPS your body: Loss of dopaminergic neurons (ie,
Tremor (pill-rolling tremor at rest) depigmentation) of substantia nigra pars
Rigidity (cogwheel) compacta.
Akinesia (or bradykinesia) Lewy bodies: composed of α-synuclein
Postural instability (intracellular eosinophilic inclusions A ).
Shuffling gait
MPTP, a contaminant in illegal drugs, is
metabolized to MPP+, which is toxic to
substantia nigra.
Huntington disease Autosomal dominant trinucleotide (CAG)n Atrophy of caudate and putamen with ex vacuo
repeat expansion in the huntingtin (HTT) ventriculomegaly.
gene on chromosome 4 (4 letters). Symptoms dopamine, GABA, ACh in brain. Neuronal
manifest between ages 20 and 50: chorea, death via NMDA-R binding and glutamate
athetosis, aggression, depression, dementia excitotoxicity.
(sometimes initially mistaken for substance
abuse).
Anticipation results from expansion of CAG
repeats. Caudate loses ACh and GABA.
Alzheimer disease Most common cause of dementia in elderly. Widespread cortical atrophy (normal cortex B ;
Down syndrome patients have risk of cortex in Alzheimer disease C ), especially
developing Alzheimer disease, as APP is hippocampus (arrows in B and C ). Narrowing
located on chromosome 21. of gyri and widening of sulci.
ACh. Senile plaques D in gray matter: extracellular
Associated with the following altered proteins: β-amyloid core; may cause amyloid angiopathy
ApoE-2: risk of sporadic form intracranial hemorrhage; Aβ (amyloid-β)
ApoE-4: risk of sporadic form synthesized by cleaving amyloid precursor
APP, presenilin-1, presenilin-2: familial protein (APP).
forms (10%) with earlier onset Neurofibrillary tangles E : intracellular,
hyperphosphorylated tau protein = insoluble
cytoskeletal elements; number of tangles
correlates with degree of dementia.
Frontotemporal Also known as Pick disease. Early changes in Frontotemporal lobe degeneration F .
dementia personality and behavior (behavioral variant), Inclusions of hyperphosphorylated tau (round
or aphasia (primary progressive aphasia). Pick bodies G ) or ubiquitinated TDP-43.
May have associated movement disorders (eg,
parkinsonism).
Lewy body dementia Visual hallucinations (“haLewycinations”), Intracellular Lewy bodies A primarily in cortex.
dementia with fluctuating cognition/
alertness, REM sleep behavior disorder, and
parkinsonism. Called Lewy body dementia if
cognitive and motor symptom onset < 1 year
apart, otherwise considered dementia 2° to
Parkinson disease.

Neurodegenerative disorders (continued)

DISEASE DESCRIPTION HISTOLOGIC/GROSS FINDINGS
Vascular dementia Result of multiple arterial infarcts and/or MRI or CT shows multiple cortical and/or
chronic ischemia. subcortical infarcts.
Step-wise decline in cognitive ability with late-
onset memory impairment. 2nd most common
cause of dementia in elderly.
Creutzfeldt-Jakob Rapidly progressive (weeks to months) dementia Spongiform cortex.
disease with myoclonus (“startle myoclonus”) and Prions (PrPc PrPsc sheet [β-pleated sheet
ataxia. Commonly see periodic sharp waves on resistant to proteases]) H .
EEG and 14-3-3 protein in CSF.
A B C D
E F G H
Idiopathic intracranial Also known as pseudotumor cerebri. ICP with no apparent cause on imaging (eg, hydrocephalus,
hypertension obstruction of CSF outflow). Risk factors include female gender, Tetracyclines, Obesity, vitamin A
excess, Danazol (female TOAD).
Findings: headache, tinnitus, diplopia (usually from CN VI palsy), no change in mental status.
Impaired optic nerve axoplasmic flow papilledema. Visual field testing shows enlarged blind
spot and peripheral constriction. Lumbar puncture reveals opening pressure and provides
temporary headache relief.
Treatment: weight loss, acetazolamide, invasive procedures for refractory cases (eg, CSF shunt
placement, optic nerve sheath fenestration surgery for visual loss).

Hydrocephalus CSF volume ventricular dilation +/− ICP.

Communicating
Communicating CSF absorption by arachnoid granulations (eg, arachnoid scarring post-meningitis) ICP,
hydrocephalus papilledema, herniation.
Normal pressure Affects the elderly; idiopathic; CSF pressure elevated only episodically; does not result in increased
hydrocephalus subarachnoid space volume. Expansion of ventricles A distorts the fibers of the corona radiata
triad of urinary incontinence, gait apraxia (magnetic gait), and cognitive dysfunction
(sometimes reversible). “Wet, wobbly, and wacky.” Symptoms potentially reversible with CSF
shunt placement.
Noncommunicating (obstructive)
Noncommunicating Caused by structural blockage of CSF circulation within ventricular system (eg, stenosis of
hydrocephalus aqueduct of Sylvius; colloid cyst blocking foramen of Monro; tumor B ).
Hydrocephalus mimics
Ex vacuo Appearance of CSF on imaging C , but is actually due to brain tissue and neuronal atrophy
ventriculomegaly (eg, Alzheimer disease, advanced HIV, Pick disease, Huntington disease). ICP is normal; NPH
triad is not seen.
A B C

Multiple sclerosis Autoimmune inflammation and demyelination of CNS (brain and spinal cord) with subsequent
axonal damage. Can present with:
Acute optic neuritis (painful unilateral visual loss associated with Marcus Gunn pupil)
Brain stem/cerebellar syndromes (eg, diplopia, ataxia, scanning speech, intention tremor,
nystagmus/INO (bilateral > unilateral)
Pyramidal tract weakness
Spinal cord syndromes (eg, electric shock-like sensation along spine on neck flexion [Lhermitte
phenomenon], neurogenic bladder, paraparesis, sensory manifestations affecting the trunk or
one or more extremity)
Symptoms may exacerbate with increased body temperature (eg, hot bath, exercise). Relapsing and
remitting is most common clinical course. Most often affects women in their 20s and 30s; more
common in Caucasians living farther from equator.
FINDINGS IgG level and myelin basic protein in CSF. Oligoclonal bands are diagnostic. MRI is gold
A standard. Periventricular plaques A (areas of oligodendrocyte loss and reactive gliosis). Multiple
white matter lesions disseminated in space and time.
TREATMENT Stop relapses and halt/slow progression with disease-modifying therapies (eg, β-interferon,
glatiramer, natalizumab). Treat acute flares with IV steroids. Symptomatic treatment for
neurogenic bladder (catheterization, muscarinic antagonists), spasticity (baclofen, GABA B
receptor agonists), pain (TCAs, anticonvulsants).

Other demyelinating and dysmyelinating disorders

Osmotic demyelination Also known as central pontine myelinolysis. Massive axonal demyelination in pontine white matter
syndrome A 2° to rapid osmotic changes, most commonly iatrogenic correction of hyponatremia but also
A
rapid shifts of other osmolytes (eg, glucose). Acute paralysis, dysarthria, dysphagia, diplopia, loss of
consciousness. Can cause “locked-in syndrome.”
Correcting serum Na+ too fast:
“From low to high, your pons will die” (osmotic demyelination syndrome).
“From high to low, your brains will blow” (cerebral edema/herniation).
Acute inflammatory Most common subtype of Guillain-Barré syndrome. Autoimmune condition associated
demyelinating with infections (eg, Campylobacter jejuni, viruses [eg, Zika]) that destroys Schwann cells by
polyradiculopathy inflammation and demyelination of peripheral nerves (including cranial nerves III-XII) and
motor fibers likely due to molecular mimicry, inoculations, and stress, but no definitive link to
pathogens.
Results in symmetric ascending muscle weakness/paralysis and depressed/absent DTRs beginning
in lower extremities. Facial paralysis (usually bilateral) and respiratory failure are common. May
see autonomic dysregulation (eg, cardiac irregularities, hypertension, hypotension) or sensory
abnormalities. Almost all patients survive; majority recover completely after weeks to months.
CSF protein with normal cell count (albuminocytologic dissociation).
Respiratory support is critical until recovery. Disease-modifying treatment: plasmapheresis, IV
immunoglobulins. No role for steroids.
Acute disseminated Multifocal inflammation and demyelination after infection or vaccination. Presents with rapidly
(postinfectious) progressive multifocal neurologic symptoms, altered mental status.
encephalomyelitis
Charcot-Marie-Tooth Also known as hereditary motor and sensory neuropathy. Group of progressive hereditary nerve
disease disorders related to the defective production of proteins involved in the structure and function of
peripheral nerves or the myelin sheath. Typically autosomal dominant inheritance pattern and
associated with foot deformities (eg, pes cavus, hammer toe), lower extremity weakness (eg, foot
drop), and sensory deficits. Most common type, CMT1A, is caused by PMP22 gene duplication.
Progressive multifocal Demyelination of CNS B due to destruction of oligodendrocytes (2° to reactivation of latent
leukoencephalopathy JC virus infection). Seen in 2–4% of patients with AIDS. Rapidly progressive, usually fatal.
B
Predominantly involves parietal and occipital areas; visual symptoms are common. risk
associated with natalizumab, rituximab.
Other disorders Krabbe disease, metachromatic leukodystrophy, adrenoleukodystrophy.

Neurocutaneous disorders
Sturge-Weber Also known as encephalotrigeminal angiomatosis. Congenital, noninherited (sporadic),
syndrome developmental anomaly of neural crest derivatives due to somatic mosaicism for an activating
mutation in one copy of the GNAQ gene. Affects small (capillary-sized) blood vessels port-wine
stain of the face A (nevus flammeus, a non-neoplastic “birthmark” in CN V1/V2 distribution);
ipsilateral leptomeningeal angioma B seizures/epilepsy; intellectual disability; and episcleral
hemangioma IOP early-onset glaucoma.
STURGE-Weber: Sporadic, port-wine Stain; Tram track calcifications (opposing gyri); Unilateral;
Retardation (intellectual disability); Glaucoma, GNAQ gene; Epilepsy.
Tuberous sclerosis TSC1 mutation on chromosome 9 or TSC2 mutation on chromosome 16. Tumor suppressor
genes. Autosomal dominant, variable expression. HAMARTOMAS: Hamartomas in CNS
and skin; Angiofibromas C ; Mitral regurgitation; Ash-leaf spots D ; cardiac Rhabdomyoma;
(Tuberous sclerosis); autosomal dOminant; Mental retardation (intellectual disability); renal
Angiomyolipoma E ; Seizures, Shagreen patches. incidence of subependymal giant cell
astrocytomas and ungual fibromas.
Neurofibromatosis Also known as von Recklinghausen disease. Mutation in NF1 tumor suppressor gene on
type I chromosome 17 (17 letters in “von Recklinghausen”), which normally codes for neurofibromin,
a negative regulator of RAS. Autosomal dominant, 100% penetrance. Café-au-lait spots F ,
cutaneous neurofibromas G , optic gliomas, pheochromocytomas, Lisch nodules (pigmented iris
hamartomas H ).
Neurofibromatosis Mutation in NF2 tumor suppressor gene on chromosome 22. Autosomal dominant. Findings:
type II bilateral acoustic schwannomas, juvenile cataracts, meningiomas, and ependymomas. NF2
affects 2 ears, 2 eyes, and 2 parts of the brain.
von Hippel-Lindau Deletion of VHL gene on chromosome 3p (VHL = 3 letters). Autosomal dominant. pVHL
disease ubiquitinates hypoxia-inducible factor 1a. Characterized by development of numerous tumors,
both benign and malignant. HARP: Hemangioblastomas (high vascularity with hyperchromatic
nuclei I ) in retina, brain stem, cerebellum, spine J ; Angiomatosis (eg, cavernous hemangiomas
in skin, mucosa, organs); bilateral Renal cell carcinomas; Pheochromocytomas.
A B C D E
F G H I J

Adult primary brain tumors

TUMOR DESCRIPTION HISTOLOGY
Glioblastoma Grade IV astrocytoma. Common, highly Astrocyte origin, GFAP ⊕. “Pseudopalisading”
multiforme malignant 1° brain tumor with ~ 1-year pleomorphic tumor cells B border central
median survival. Found in cerebral areas of necrosis, hemorrhage, and/or
hemispheres A . Can cross corpus callosum microvascular proliferation.
(“butterfly glioma”).
Oligodendroglioma Relatively rare, slow growing. Most often in Oligodendrocyte origin. “Fried egg” cells—
frontal lobes C . “Chicken-wire” capillary round nuclei with clear cytoplasm D . Often
pattern. calcified.
Meningioma Common, typically benign. Females > males. Arachnoid cell origin. Spindle cells
Most often occurs near surfaces of brain and concentrically arranged in a whorled
in parasagittal region. Extra-axial (external pattern; psammoma bodies F (laminated
to brain parenchyma) and may have a dural calcifications).
attachment (“tail” E ). Often asymptomatic;
may present with seizures or focal neurologic
signs. Resection and/or radiosurgery.
Hemangioblastoma Most often cerebellar G . Associated with von Blood vessel origin. Closely arranged, thin-
Hippel-Lindau syndrome when found with walled capillaries with minimal intervening
retinal angiomas. Can produce erythropoietin parenchyma H .
2° polycythemia.
Pituitary adenoma Adenoma may be nonfunctioning (silent) or Hyperplasia of only one type of endocrine cells
hyperfunctioning (hormone producing). Most found in pituitary (ie, lactotroph, gonadotroph,
commonly from lactotrophs (prolactinoma) somatotroph, corticotroph).
I hyperprolactinemia; less commonly Prolactinoma in women classically presents as
adenoma of somatotrophs (GH) acromegaly/ galactorrhea, amenorrhea, and bone density
gigantism; corticotrophs (ACTH) Cushing due to suppression of estrogen. Prolactinoma
disease. Rarely, adenoma of thyrotrophs (TSH) in men classically presents as low libido and
and gonadotroph (FSH, LH). Nonfunctional infertility.
tumors present with mass effect (bitemporal Treatment: dopamine agonists (eg,
hemianopia, hypopituitarism, headache). bromocriptine, cabergoline), transsphenoidal
Bitemporal hemianopia due to pressure on resection.
optic chiasm ( J shows normal visual field
above, patient’s perspective below). Sequelae
include hyper- or hypopituitarism, which may
be caused by pituitary apoplexy.
Schwannoma Classically at the cerebellopontine angle K Schwann cell origin L , S-100 ⊕. Biphasic.
involving both CNs VII and VIII, but can be Dense, hypercellular areas containing spindle
along any peripheral nerve. Often localized cells alternating with hypocellular, myxoid
to CN VIII in internal acoustic meatus areas.
→ vestibular schwannoma. Bilateral vestibular
schwannomas found in NF-2. Resection or
stereotactic radiosurgery.

Adult primary brain tumors (continued)

A B C D
E F G H
I J K L

Childhood primary brain tumors

TUMOR DESCRIPTION HISTOLOGY
Pilocytic astrocytoma Low-grade astrocytoma. Most common 1° Glial cell origin, GFAP ⊕. Rosenthal
brain tumor in childhood. Usually well fibers—eosinophilic, corkscrew fibers B .
circumscribed. In children, most often found Cystic + solid (gross).
in posterior fossa A (eg, cerebellum). May be
supratentorial. Benign; good prognosis.
Medulloblastoma Most common malignant brain tumor in Form of primitive neuroectodermal tumor
childhood. Commonly involves cerebellum (PNET). Homer-Wright rosettes, small blue
C . Can compress 4th ventricle, causing cells D .
noncommunicating hydrocephalus
headaches, papilledema. Can send “drop
metastases” to spinal cord.
Ependymoma Most commonly found in 4th ventricle E . Can Ependymal cell origin. Characteristic
cause hydrocephalus. Poor prognosis. perivascular pseudorosettes F . Rod-shaped
blepharoplasts (basal ciliary bodies) found near
the nucleus.
Craniopharyngioma Most common childhood supratentorial tumor. Derived from remnants of Rathke pouch
May be confused with pituitary adenoma (ectoderm). Calcification is common G H .
(both cause bitemporal hemianopia). Cholesterol crystals found in “motor oil”-like
fluid within tumor.
Pinealoma Tumor of pineal gland. Can cause Parinaud Similar to germ cell tumors (eg, testicular
syndrome (compression of tectum → vertical seminoma).
gaze palsy); obstructive hydrocephalus
(compression of cerebral aqueduct); precocious
puberty in males (β-hCG production).
A B C D
E F G H

Herniation syndromes C
ingulate (subfalcine) herniation under Can compress anterior cerebral artery.
Falx cerebri falx cerebri
Lateral Transtentorial (central/downward) Caudal displacement of brain stem rupture of
ventricles
herniation paramedian basilar artery branches Duret
Supratentorial
mass hemorrhages. Usually fatal.
Uncus
Tentorium Uncal herniation Uncus = medial temporal lobe. Herniation
cerebelli compresses ipsilateral CN III and contralateral
Kernohan crus cerebri against Kernohan notch (causes
Duret notch
hemorrhage contralateral CN III palsy and/or ipsilateral
hemiparesis, ie, a false localizing sign).
C
erebellar tonsillar herniation into the Coma and death result when these herniations
foramen magnum compress the brain stem.
Motor neuron signs

SIGN UMN LESION LMN LESION COMMENTS
Weakness + + Lower motor neuron = everything lowered
Atrophy − + (less muscle mass, muscle tone, reflexes,
downgoing toes).
Fasciculations − +
Upper motor neuron = everything up (tone,
Reflexes DTRs, toes).
Tone Fasciculations = muscle twitching.
Babinski + − Positive Babinski is normal in infants.
Spastic paresis + −
Flaccid paralysis − +
Clasp knife spasticity + −

Spinal cord lesions

AREA AFFECTED DISEASE CHARACTERISTICS
Spinal muscular atrophy Congenital degeneration of anterior horns of spinal
cord. LMN lesions only, symmetric weakness.
“Floppy baby” with marked hypotonia (Flaccid
paralysis) and tongue Fasciculations. Autosomal
recessive inheritance of mutation in SMN1.
SMA type 1 is called Werdnig-Hoffmann disease.
Amyotrophic lateral sclerosis Combined UMN (corticobulbar/corticospinal) and
LMN (medullary and spinal cord) degeneration.
No sensory or bowel/bladder deficits.
Can be caused by defect in superoxide dismutase 1.
LMN deficits due to anterior horn cell involvement
(eg, dysarthria, dysphagia, asymmetric limb
weakness, fasciculations, atrophy) and UMN deficits
Posterior spinal arteries
(pseudobulbar palsy, eg, dysarthria, dysphagia,
emotional lability, spastic gait, clonus). Fatal.
Commonly known as Lou Gehrig disease.
Treatment: riluzole.
Posterior
Posteriorspinal
spinal arteries
arteries Complete occlusion of anterior Spares dorsal columns and Lissauer tract; mid-
spinal artery thoracic ASA territory is watershed area, as artery
of Adamkiewicz supplies ASA below T8. Can be
Anterior spinal artery
caused by aortic aneurysm repair. Presents with
UMN deficit below the lesion (corticospinal tract),
Anterior spinal artery LMN deficit at the level of the lesion (anterior horn),
Anterior
and loss of pain and temperature sensation below
Anteriorspinal
spinal artery
artery
Anterior spinal artery the lesion (spinothalamic tract).
Tabes dorsalis Caused by 3° syphilis. Results from degeneration
(demyelination) of dorsal columns and roots
progressive sensory ataxia (impaired
proprioception poor coordination).
⊕ Romberg sign and absent DTRs.
Associated with Charcot joints, shooting pain, Argyll
Robertson pupils.
Syringomyelia Syrinx expands and damages anterior white
commissure of spinothalamic tract (2nd-order
neurons) bilateral symmetrical loss of pain and
temperature sensation in cape-like distribution. Seen
with Chiari I malformation. Can affect other tracts.
Vitamin B12 deficiency Subacute combined degeneration (SCD)—
demyelination of Spinocerebellar tracts, lateral
Corticospinal tracts, and Dorsal columns. Ataxic
gait, paresthesia, impaired position/vibration sense.
Cauda equina syndrome Compression of spinal roots L2 and below, often due
to intervertebral disc herniation or tumor.
Unilateral radicular pain, absent knee and ankle
reflex, loss of bladder and anal sphincter control,
saddle anesthesia.
Treatment: emergent surgery and steroids.

Poliomyelitis Caused by poliovirus (fecal-oral transmission). Replicates in oropharynx and small intestine before
spreading via bloodstream to CNS. Infection causes destruction of cells in anterior horn of spinal
cord (LMN death).
Signs of LMN lesion: asymmetric weakness, hypotonia, flaccid paralysis, fasciculations,
hyporeflexia, muscle atrophy. Respiratory muscle involvement leads to respiratory failure. Signs of
infection: malaise, headache, fever, nausea, etc.
CSF shows WBCs (lymphocytic pleocytosis) and slight of protein (with no change in CSF
glucose). Virus recovered from stool or throat.
Brown-Séquard Hemisection of spinal cord. Findings:

syndrome I psilateral loss of all sensation at level of
lesion
Ipsilateral LMN signs (eg, flaccid paralysis) at Level of lesion
level of lesion
Loss of
I psilateral UMN signs below level of lesion sensation
(due to corticospinal tract damage) LMN signs
Ipsilateral loss of proprioception, vibration,
light (2-point discrimination) touch, and
tactile sense below level of lesion (due to
UMN signs
dorsal column damage). Impaired pain,
Impaired temperature,
Contralateral loss of pain, temperature, and proprioception, crude touch
crude (nonadiscriminative) touch below level vibration, light sensation
touch,
of lesion (due to spinothalamic tract damage) tactile sense
If lesion occurs above T1, patient may present
with ipsilateral Horner syndrome due to
damage of oculosympathetic pathway.
Friedreich ataxia Autosomal recessive trinucleotide repeat disorder Friedreich is Fratastic (frataxin): he’s your
(GAA)n on chromosome 9 in gene that favorite frat brother, always staggering and
encodes frataxin (iron binding protein). Leads falling but has a sweet, big heart.
to impairment in mitochondrial functioning. Ataxic GAAit.
Degeneration of lateral corticospinal tract A B
(spastic paralysis), spinocerebellar tract
(ataxia), dorsal columns ( vibratory sense,
proprioception), and dorsal root ganglia
(loss of DTRs). Staggering gait, frequent
falling, nystagmus, dysarthria, pes cavus,
hammer toes, diabetes mellitus, hypertrophic
cardiomyopathy (cause of death). Presents in
childhood with kyphoscoliosis A B .

Common cranial nerve lesions

CN V motor lesion Jaw deviates toward side of lesion due to unopposed force from the opposite pterygoid muscle.
CN X lesion Uvula deviates away from side of lesion. Weak side collapses and uvula points away.
CN XI lesion Weakness turning head to contralateral side of lesion (SCM). Shoulder droop on side of lesion
(trapezius).
The left SCM contracts to help turn the head to the right.
CN XII lesion LMN lesion. Tongue deviates toward side of lesion (“lick your wounds”) due to weakened tongue
muscles on affected side.
Facial nerve lesions Bell palsy is the most common cause of peripheral facial palsy A . Usually develops after HSV
A
reactivation. Treatment: corticosteroids ± acyclovir. Most patients gradually recover function, but
aberrant regeneration can occur. Other causes of peripheral facial palsy include Lyme disease,
herpes zoster (Ramsay Hunt syndrome), sarcoidosis, tumors (eg, parotid gland), diabetes mellitus.
Upper motor neuron lesion Lower motor neuron lesion

LESION LOCATION Motor cortex, connection from motor cortex to Facial nucleus, anywhere along CN VII
facial nucleus in pons
AFFECTED SIDE Contralateral Ipsilateral
MUSCLES INVOLVED Lower muscles of facial expression Upper and lower muscles of facial expression
FOREHEAD INVOLVED? Spared, due to bilateral UMN innervation Affected
OTHER SYMPTOMS None Incomplete eye closure (dry eyes, corneal
ulceration), hyperacusis, loss of taste sensation
to anterior tongue
Face area of
motor cortex
Corticobulbar tract
(UMN lesion—central)
Upper
division Facial
Lower nucleus
division
CN VII
(LMN lesion—peripheral;
cannot wrinkle forehead)

neurology—Otology SEC TION III 517
NEUROLOGY—OTOLOGY
``
Auditory physiology
Outer ear Visible portion of ear (pinna), includes auditory canal and tympanic membrane. Transfers sound
waves via vibration of tympanic membrane.
Middle ear Air-filled space with three bones called the ossicles (malleus, incus, stapes). Ossicles conduct and
amplify sound from tympanic membrane to inner ear.
Inner ear Snail-shaped, fluid-filled cochlea. Contains basilar membrane that vibrates 2° to sound waves.
Vibration transduced via specialized hair cells auditory nerve signaling brain stem.
Each frequency leads to vibration at specific location on basilar membrane (tonotopy):
Low frequency heard at apex near helicotrema (wide and flexible).
High frequency heard best at base of cochlea (thin and rigid).
Diagnosing hearing loss

WEBER TEST RINNE TEST
Conductive hearing Localizes to affected ear Abnormal (bone > air)
loss
Sensorineural hearing Localizes to unaffected ear Normal (air > bone)
loss
Types of hearing loss

Noise-induced Damage to stereociliated cells in organ of Corti. Loss of high-frequency hearing first. Sudden
hearing loss extremely loud noises can produce hearing loss due to tympanic membrane rupture.
Presbycusis Aging-related progressive bilateral/symmetric sensorineural hearing loss (often of higher
frequencies) due to destruction of hair cells at the cochlear base (preserved low-frequency hearing
at apex).
Cholesteatoma Overgrowth of desquamated keratin debris within the middle ear space ( A , arrows); may erode
A
ossicles, mastoid air cells conductive hearing loss. Often presents with painless otorrhea.

neurology—OPHTHALMOLOGY
Vertigo Sensation of spinning while actually stationary. Subtype of “dizziness,” but distinct from
“lightheadedness.”
Peripheral vertigo More common. Inner ear etiology (eg, semicircular canal debris, vestibular nerve infection,
Ménière disease [triad: sensorineural hearing loss, vertigo, tinnitus], benign paroxysmal positional
vertigo [BPPV]). Treatment: antihistamines, anticholinergics, antiemetics (symptomatic relief);
low-salt diet ± diuretics (Ménière disease); Epley maneuver (BPPV).
Central vertigo Brain stem or cerebellar lesion (eg, stroke affecting vestibular nuclei or posterior fossa tumor).
Findings: directional or purely vertical nystagmus, skew deviation, diplopia, dysmetria. Focal
neurologic findings.
NEUROLOGY—OPHTHALMOLOGY
``
Normal eye
A
Sclera (outer)
Physiologic cup
Macula Ciliary body (middle) Choroid (middle)

Optic disc
Fovea Zonular fibers Retina A (inner)
Retinal artery Cornea (outer)

Retinal vein
Iris (middle) Vitreous chamber
Fovea
Pupil
Optic disc
Lens Optic
Anterior chamber nerve
Posterior chamber
Central Central
retinal retinal
vein artery
ANTERIOR SEGMENT POSTERIOR SEGMENT

(anterior chamber + posterior chamber)
Conjunctivitis Inflammation of the conjunctiva red eye A .

A Allergic—itchy eyes, bilateral.
Bacterial—pus; treat with antibiotics.
Viral—most common, often adenovirus; sparse mucous discharge, swollen preauricular node; self-
resolving.

neurology—OPHTHALMOLOGY SEC TION III 519
Refractive errors Common cause of impaired vision, correctable with glasses.

Hyperopia Also known as “farsightedness.” Eye too short for refractive power of cornea and lens light
focused behind retina. Correct with convex (converging) lenses.
Myopia Also known as “nearsightedness.” Eye too long for refractive power of cornea and lens light
focused in front of retina. Correct with concave (diverging) lens.
Astigmatism Abnormal curvature of cornea different refractive power at different axes. Correct with
cylindrical lens.
Presbyopia Aging-related impaired accommodation (focusing on near objects), primarily due to lens
elasticity, changes in lens curvature, strength of the ciliary muscle. Patients often need “reading
glasses” (magnifiers).
Cataract Painless, often bilateral, opacification of lens A , often resulting in glare and vision, especially
A at night. Acquired risk factors: age, smoking, excessive alcohol use, excessive sunlight,
prolonged corticosteroid use, diabetes mellitus, trauma, infection. Congenital risk factors: classic
galactosemia, galactokinase deficiency, trisomies (13, 18, 21), ToRCHeS infections (eg, rubella),
Marfan syndrome, Alport syndrome, myotonic dystrophy, neurofibromatosis 2.
Aqueous humor
pathway “Angle” of the eye nea
Cor
Trabecular outflow (90%) Anterior chamber

Drainage through trabecular meshwork 
canal of Schlemm  episcleral vasculature Episcleral
( with M 3 agonist) vessel ork
eshw
Canal of l ar m
Schlemm abec u Posterior chamber
Tr
Uveoscleral outflow (10%)

Iris Iris
Drainage into uvea and sclera era
( with prostaglandin Scl Dilator muscle (α1)
agonists) Sphincter muscle (M 3)
Lens Lens
Suspended from ciliary body
Ciliary body by zonule fibers. Muscular fibers
in ciliary body affect lens shape
for accommodation.
Aqueous humor
Produced by nonpigmented epithelium Vitreous chamber
on ciliary body ( by β-blockers, α2-agonists,
and carbonic anhydrase inhibitors)

Glaucoma Optic disc atrophy with characteristic cupping (thinning of outer rim of optic nerve head B versus
normal A ), usually with elevated intraocular pressure (IOP) and progressive peripheral visual field
loss if untreated. Treatment is through pharmacologic or surgical lowering of IOP.
Open-angle glaucoma Associated with age, African-American race, family history. Painless, more common in US.
Primary—cause unclear.
Secondary—blocked trabecular meshwork from WBCs (eg, uveitis), RBCs (eg, vitreous
hemorrhage), retinal elements (eg, retinal detachment).
Closed- or narrow- Primary—enlargement or anterior movement of lens against central iris (pupil margin)
angle glaucoma obstruction of normal aqueous flow through pupil fluid builds up behind iris, pushing
peripheral iris against cornea C and impeding flow through trabecular meshwork.
Secondary—hypoxia from retinal disease (eg, diabetes mellitus, vein occlusion) induces
vasoproliferation in iris that contracts angle.
Chronic closure—often asymptomatic with damage to optic nerve and peripheral vision.
Acute closure—true ophthalmic emergency. IOP pushes iris forward angle closes abruptly.
Very painful, red eye D , sudden vision loss, halos around lights, frontal headache, fixed and
mid‑dilated pupil. Mydriatic agents contraindicated.
A B C D
Normal
Normal Cupping Angle closure Acute angle closure
Uveitis Inflammation of uvea; specific name based on location within affected eye. Anterior uveitis: iritis;
A
posterior uveitis: choroiditis and/or retinitis. May have hypopyon (accumulation of pus in anterior
chamber A ) or conjunctival redness. Associated with systemic inflammatory disorders (eg,
sarcoidosis, rheumatoid arthritis, juvenile idiopathic arthritis, HLA-B27–associated conditions).
Age-related macular Degeneration of macula (central area of retina). Causes distortion (metamorphopsia) and eventual
degeneration loss of central vision (scotomas).
A
Dry (nonexudative, > 80%)—Deposition of yellowish extracellular material in between Bruch
membrane and retinal pigment epithelium (“Drusen”) A with gradual in vision. Prevent
progression with multivitamin and antioxidant supplements.
Wet (exudative, 10–15%)—rapid loss of vision due to bleeding 2° to choroidal
neovascularization. Treat with anti-VEGF (vascular endothelial growth factor) injections
(eg, bevacizumab, ranibizumab).

Diabetic retinopathy Retinal damage due to chronic hyperglycemia. Two types:

A
Nonproliferative—damaged capillaries leak blood lipids and fluid seep into retina
hemorrhages (arrows in A ) and macular edema. Treatment: blood sugar control.
Proliferative—chronic hypoxia results in new blood vessel formation with resultant traction on
retina. Treatment: peripheral retinal photocoagulation, surgery, anti-VEGF.
Hypertensive Retinal damage due to chronic uncontrolled HTN.

retinopathy Flame-shaped retinal hemorrhages, arteriovenous nicking, microaneurysms, macular star (exudate,
A
red arrow in A ), cotton-wool spots (blue arrow in A ). Presence of papilledema requires immediate
lowering of BP.
Associated with risk of stroke, CAD, kidney disease.
Retinal vein occlusion Blockage of central or branch retinal vein due to compression from nearby arterial atherosclerosis.
A
Retinal hemorrhage and venous engorgement (“blood and thunder appearance”; arrows in A ),
edema in affected area.
Retinal detachment Separation of neurosensory layer of retina (photoreceptor layer with rods and cones) from
A
outermost pigmented epithelium (normally shields excess light, supports retina) degeneration
of photoreceptors vision loss. May be 2° to retinal breaks, diabetic traction, inflammatory
effusions. Visualized on fundoscopy as crinkling of retinal tissue A and changes in vessel
direction.
Breaks more common in patients with high myopia and/or history of head trauma. Often preceded
by posterior vitreous detachment (“flashes” and “floaters”) and eventual monocular loss of vision
like a “curtain drawn down.” Surgical emergency.

Central retinal artery Acute, painless monocular vision loss. Retina cloudy with attenuated vessels and “cherry-red” spot
occlusion at fovea (center of macula) A . Evaluate for embolic source (eg, carotid artery atherosclerosis,
A
cardiac vegetations, patent foramen ovale).
Retinitis pigmentosa Inherited retinal degeneration. Painless, progressive vision loss beginning with night blindness (rods
A
affected first). Bone spicule-shaped deposits around macula A .
Retinitis Retinal edema and necrosis (arrows in A ) leading to scar. Often viral (CMV, HSV, VZV), but can
A
be bacterial or parasitic. May be associated with immunosuppression.
Papilledema Optic disc swelling (usually bilateral) due to ICP (eg, 2° to mass effect). Enlarged blind spot and
A elevated optic disc with blurred margins A .

Pupillary control
Miosis Constriction, parasympathetic:
1st neuron: Edinger-Westphal nucleus to ciliary ganglion via CN III
2nd neuron: short ciliary nerves to sphincter pupillae muscles
Short ciliary nerves shorten the pupil diameter.
Pupillary light reflex Light in either retina sends a signal via CN II Visual field L eye Visual field R eye
to pretectal nuclei (dashed lines in image)
in midbrain that activates bilateral Edinger- Sphincter
Light Light
Westphal nuclei; pupils constrict bilaterally Nasal
retina
pupillae
muscles
(direct and consensual reflex). Temporal
Result: illumination of 1 eye results in bilateral retina Optic nerve
(CN II) Ciliary
pupillary constriction. Optic ganglion
chiasm
Edinger- Oculomotor
Westphal nerve (CN III)
nucleus
Lateral
geniculate
nucleus
Pretectal
nuclei
Mydriasis Dilation, sympathetic:

1st neuron: hypothalamus to ciliospinal center of Budge (C8–T2)
2nd neuron: exit at T1 to superior cervical ganglion (travels along cervical sympathetic chain
near lung apex, subclavian vessels)
3rd neuron: plexus along internal carotid, through cavernous sinus; enters orbit as long ciliary
nerve to pupillary dilator muscles. Sympathetic fibers also innervate smooth muscle of eyelids
(minor retractors) and sweat glands of forehead and face.
Long ciliary nerves make the pupil diameter longer.
Marcus Gunn pupil When the light shines into a normal eye, constriction of the ipsilateral (direct reflex) and
contralateral eye (consensual reflex) is observed. When the light is then swung to the affected eye,
both pupils dilate instead of constrict due to impaired conduction of light signal along the injured
optic nerve.

Horner syndrome Sympathetic denervation of face : PAM is horny (Horner).

Ptosis (slight drooping of eyelid: superior
Hypothalamus Ophthalmic division
tarsal muscle) of trigeminal nerve
Anhidrosis (absence of sweating) and Long ciliary nerve
flushing of affected side of face To sweat glands

Miosis (pupil constriction) of forehead
Associated with lesions along the sympathetic To smooth muscle of eyelid

To pupillary dilator
chain: Internal
carotid To sweat glands of face
1st neuron: pontine hemorrhage, lateral artery
External carotid artery
medullary syndrome, spinal cord lesion C2
Third neuron
above T1 (eg, Brown-Séquard syndrome, First neuron
Superior cervical ganglion
late-stage syringomyelia)
Synapse is
2nd neuron (stellate ganglion): Pancoast in lateral horn T1
tumor Second neuron
3rd neuron: carotid dissection (painful) Spinal cord
Ocular motility
Superior Superior Superior Superior CN VI innervates the Lateral Rectus.
rectus oblique rectus oblique
muscle muscle muscle muscle
CN IV innervates the Superior Oblique.
Medial CN III innervates the Rest.
Trochlea
rectus The “chemical formula” LR6SO4R3.
muscle
Lateral Medial The strongest action of the superior oblique
rectus rectus
muscle muscle is depression when the eye is adducted. The
further the eye is abducted, the more the
Lateral superior oblique acts to intort the eye toward
Inferior Inferior
oblique rectus
rectus the nose.
muscle
muscle muscle
Inferior Inferior
rectus oblique
muscle muscle
To test each muscle, ask patient to move his/

her eye in the path diagrammed to the right,
from neutral position toward the muscle being
tested. Obliques go Opposite (left SO and IO tested
with patient looking right).
IOU: IO tested looking Up.

CN III, IV, VI palsies

CN III damage CN III has both motor (central) and A
parasympathetic (peripheral) components.
Common causes include:
Ischemia pupil sparing
Uncal herniation coma
PCA aneurysm sudden-onset headache
Cavernous sinus thrombosis proptosis,
involvement of CNs IV, V1/V2, VI
Midbrain stroke contralateral hemiplegia
Motor output to extraocular muscles—affected
primarily by vascular disease (eg, diabetes
mellitus: glucose sorbitol) due to diffusion
of oxygen and nutrients to the interior fibers
from compromised vasculature that resides on
CN III outside of nerve. Signs: ptosis, “down and out”
gaze.
Parasympathetic output—fibers on the periphery
are first affected by compression (eg, PCom
aneurysm, uncal herniation). Signs: diminished
or absent pupillary light reflex, “blown pupil”
often with “down-and-out” gaze A .
CN IV damage Eye moves upward, particularly with contralateral B
gaze B ( going down stairs, head may tilt in
the opposite direction to compensate).
Can’t see the floor with CN IV damage.
CN VI damage Affected eye unable to abduct and is displaced C

medially in primary position of gaze C .

Visual field defects 1. Right anopia Defect in visual field of

2. Bitemporal hemianopia L eye R eye
(pituitary lesion, chiasm)

1
3. Left homonymous hemianopia Lt.
Optic
Rt.
7 Macula
4. Left upper quadrantanopia Optic
nerve
1 3 Optic tract
2 1. Right anopia
(right temporal lesion, MCA) chiasm

2 4
2. Bitemporal hemianopsia
3. Left homonymous
Lateral 3
5. Left lower quadrantanopia geniculate
Meyer hemianopia
loop 4. Left upper quadrantic
(right parietal lesion, MCA) body
(temporal 4 anopsia (right temporal lesion)
Dorsal optic 5 lobe) 5. Left lower quadrantic
6. Left hemianopia with macular sparing radiation anopia (right parietal lesion)
(parietal 5
(PCA infarct) lobe)
6. Left hemianopsia with
macular sparing
3 (6 if
7. Central scotoma (eg, macular degeneration) Visual PCA infarct) 6 7. Central scotoma (macular
degeneration)
Calcarine cortex
fissure
7
Meyer Loop—Lower retina; Loops around
inferior horn of Lateral ventricle.
Note: When an image hits 1° visual cortex, it is upside
Dorsal optic radiation—superior retina; takes down and left-right reversed.
shortest path via internal capsule.
Cavernous sinus Collection of venous sinuses on either side of pituitary. Blood from eye and superficial cortex
cavernous sinus internal jugular vein.
CNs III, IV, V1, VI, and V2 plus postganglionic sympathetic pupillary fibers en route to orbit all
pass through cavernous sinus. Cavernous portion of internal carotid artery is also here.
Cavernous sinus syndrome—presents with variable ophthalmoplegia, corneal sensation, Horner
syndrome and occasional decreased maxillary sensation. 2° to pituitary tumor mass effect,
carotid-cavernous fistula, or cavernous sinus thrombosis related to infection. CN VI is most
susceptible to injury.
3rd ventricle
Anterior cerebral a.
Optic chiasma CN II
Internal carotid a.
Subarachnoid space
Oculomotor n. (CN III)
Trochlear n. (CN IV)

Cavernous sinus
Pituitary
Ophthalmic n. (CN V1)
Pia
Maxillary n. (CN V2) Arachnoid
Dura
Abducens n. (CN VI)
Sphenoid
sinus

Internuclear Medial longitudinal fasciculus (MLF): pair of MLF in MS.

ophthalmoplegia tracts that allows for crosstalk between CN VI When looking left, the left nucleus of CN VI
and CN III nuclei. Coordinates both eyes to fires, which contracts the left lateral rectus and
move in same horizontal direction. Highly stimulates the contralateral (right) nucleus of
myelinated (must communicate quickly so eyes CN III via the right MLF to contract the right
move at same time). Lesions may be unilateral medial rectus.
or bilateral (latter classically seen in multiple Directional term (eg, right INO, left INO) refers
sclerosis). to which eye is paralyzed.
Lesion in MLF = internuclear ophthalmoplegia INO = Ipsilateral adduction failure, Nystagmus
(INO), a conjugate horizontal gaze palsy. Lack Opposite.
of communication such that when CN VI
nucleus activates ipsilateral lateral rectus,
contralateral CN III nucleus does not stimulate
medial rectus to contract. Abducting eye
gets nystagmus (CN VI overfires to stimulate
CN III). Convergence normal.
Lateral Medial recti Lateral Right INO (right MLF lesion)
rectus rectus
L R
Left gaze
Left MLF Right MLF Impaired adduction Nystagmus

(convergence normal)
Medial rectus Nuclei

subnucleus of CN VI
of CN III

neurology—Pharmacology
NEUROLOGY—PHARMACOLOGY
``
Epilepsy drugs
GENERALIZED
PARTIAL (FOCAL)
TONIC-CLONIC
EPILEPTICUS
ABSENCE
STATUS
MECHANISM SIDE EFFECTS NOTES
Benzodiazepines ** GABA A action Sedation, tolerance, Also for eclampsia seizures (1st
✓ dependence, respiratory line is MgSO4)
depression
Carbamazepine * ✓ Blocks Na+ channels Diplopia, ataxia, blood 1st line for trigeminal neuralgia
✓ dyscrasias (agranulocytosis,
aplastic anemia), liver
toxicity, teratogenesis (cleft
lip/palate, spina bifida),
induction of cytochrome
P-450, SIADH, Stevens-
Johnson syndrome
Ethosuximide * Blocks thalamic T-type Ca2+ EFGHIJ—Ethosuximide Sucks to have Silent
✓ channels causes Fatigue, GI distress, (absence) Seizures
Headache, Itching (and
urticaria), and Stevens-
Johnson syndrome
Gabapentin ✓ Primarily inhibits high-voltage- Sedation, ataxia Also used for peripheral
activated Ca2+ channels; neuropathy, postherpetic
designed as GABA analog neuralgia
Lamotrigine ✓ ✓ ✓ Blocks voltage-gated Na+ Stevens-Johnson syndrome
channels, inhibits the release (must be titrated slowly)
of glutamate
Levetiracetam ✓ ✓ Unknown; may modulate Neuropsychiatric symptoms
GABA and glutamate release (eg, personality change),
fatigue, drowsiness,
headache
Phenobarbital ✓ ✓ ✓ GABA A action Sedation, tolerance, 1st line in neonates
dependence, induction (“phenobabytal”)
of cytochrome P-450,
cardiorespiratory depression
Phenytoin, ✓ * *** Blocks Na+ channels; zero- PHENYTOIN: P450 induction, Hirsutism, Enlarged
fosphenytoin ✓ ✓ order kinetics gums, Nystagmus, Yellow-brown skin, Teratogenicity (fetal
hydantoin syndrome), Osteopenia, Inhibited folate absorption,
Neuropathy. Rare adverse reactions including Stevens-Johnson
syndrome, DRESS syndrome, SLE-like syndrome. Toxicity
leads to diplopia, ataxia, sedation.
Tiagabine ✓ GABA by inhibiting reuptake
Topiramate ✓ ✓ Blocks Na+ channels, GABA Sedation, mental dulling, Also used for migraine
action word-finding difficulty, prevention
kidney stones, weight loss,
glaucoma
Valproic acid ✓ * ✓ Na+ channel inactivation, GI distress, rare but fatal Also used for myoclonic seizures,
✓ GABA concentration hepatotoxicity (measure bipolar disorder, migraine
by inhibiting GABA LFTs), pancreatitis, neural prophylaxis
transaminase tube defects, tremor, weight
gain, contraindicated in
pregnancy
Vigabatrin ✓ GABA. Irreversible GABA Permanent visual loss (black
transaminase inhibitor box warning)
* = Common use, ** = 1st line for acute, *** = 1st line for recurrent seizure prophylaxis.

neurology—Pharmacology SEC TION III 529
Barbiturates Phenobarbital, pentobarbital, thiopental, secobarbital.

MECHANISM Facilitate GABA A action by duration of Cl− channel opening, thus neuron firing (barbidurates
duration).
CLINICAL USE Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental).
ADVERSE EFFECTS Respiratory and cardiovascular depression (can be fatal); CNS depression (can be exacerbated by
alcohol use); dependence; drug interactions (induces cytochrome P-450).
Overdose treatment is supportive (assist respiration and maintain BP).
Contraindicated in porphyria.
Benzodiazepines Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide,

alprazolam.
MECHANISM Facilitate GABA A action by frequency of “Frenzodiazepines” frequency.
Cl− channel opening. REM sleep. Most Benzos, barbs, and alcohol all bind the
have long half-lives and active metabolites GABA A receptor, which is a ligand-gated Cl−
(exceptions [ATOM]: Alprazolam, Triazolam, channel.
Oxazepam, and Midazolam are short acting Oxazepam, Temazepam, and Lorazepam are
higher addictive potential). OK for Terrible Livers: they can be used to treat
CLINICAL USE Anxiety, spasticity, status epilepticus (lorazepam, alcohol withdrawal in patients with liver disease
diazepam, midazolam), eclampsia, due to minimal first-pass metabolism.
detoxification (especially alcohol withdrawal–
DTs), night terrors, sleepwalking, general
anesthetic (amnesia, muscle relaxation),
hypnotic (insomnia).
ADVERSE EFFECTS Dependence, additive CNS depression effects
with alcohol. Less risk of respiratory depression
and coma than with barbiturates.
Treat overdose with flumazenil (competitive
antagonist at GABA benzodiazepine receptor).
Can precipitate seizures by causing acute
benzodiazepine withdrawal.
Nonbenzodiazepine Zolpidem, Zaleplon, esZopiclone. “These ZZZs put you to sleep.”

hypnotics
MECHANISM Act via the BZ1 subtype of the GABA receptor. Effects reversed by flumazenil. Sleep cycle less
affected as compared with benzodiazepine hypnotics.
CLINICAL USE Insomnia.
ADVERSE EFFECTS Ataxia, headaches, confusion. Short duration because of rapid metabolism by liver enzymes. Unlike
older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic
effects. dependence risk than benzodiazepines.

Suvorexant
MECHANISM Orexin (hypocretin) receptor antagonist.
ADVERSE EFFECTS CNS depression, headache, dizziness, abnormal dreams, upper respiratory tract infection.
Contraindicated in patients with narcolepsy. Not recommended in patients with liver disease. No
or low physical dependence. Contraindicated with strong CYP3A4 inhibitors.
Ramelteon
MECHANISM Melatonin receptor agonist, binds MT1 and MT2 in suprachiasmatic nucleus.
ADVERSE EFFECTS Dizziness, nausea, fatigue, headache. No dependence (not a controlled substance).
Triptans Sumatriptan
MECHANISM 5-HT1B/1D agonists. Inhibit trigeminal nerve A sumo wrestler trips and falls on your head.
activation; prevent vasoactive peptide release;
induce vasoconstriction.
CLINICAL USE Acute migraine, cluster headache attacks.
ADVERSE EFFECTS Coronary vasospasm (contraindicated in
patients with CAD or Prinzmetal angina),
mild paresthesia, serotonin syndrome (in
combination with other 5-HT agonists).

Parkinson disease Parkinsonism is due to loss of dopaminergic neurons and excess cholinergic activity.
drugs Bromocriptine, Amantadine, Levodopa (with carbidopa), Selegiline (and COMT inhibitors),
Antimuscarinics (BALSA).
STRATEGY AGENTS
Dopamine agonists Ergot—Bromocriptine.
Non-ergot (preferred)—pramipexole, ropinirole; toxicity includes impulse control disorder (eg,
gambling), postural hypotension, hallucinations/confusion.
dopamine availability Amantadine ( dopamine release and dopamine reuptake); toxicity = ataxia, livedo reticularis.
l-DOPA availability Agents prevent peripheral (pre-BBB) l-DOPA degradation l-DOPA entering CNS central
l-DOPA available for conversion to dopamine.
Levodopa (l-DOPA)/carbidopa—carbidopa blocks peripheral conversion of l-DOPA to
dopamine by inhibiting DOPA decarboxylase. Also reduces side effects of peripheral l-DOPA
conversion into dopamine (eg, nausea, vomiting).
Entacapone prevents peripheral l-DOPA degradation to 3-O-methyldopa (3‑OMD) by
inhibiting COMT. Used in conjunction with levodopa.
Prevent dopamine Agents act centrally (post-BBB) to inhibit breakdown of dopamine.
breakdown Selegiline, rasagiline—block conversion of dopamine into DOPAC by selectively inhibiting
MAO-B.
Entacapone—blocks conversion of dopamine to 3-methoxytyramine (3-MT) by inhibiting
central COMT.
Curb excess cholinergic Benztropine, trihexyphenidyl (Antimuscarinic; improves tremor and rigidity but has little effect on
activity bradykinesia in Parkinson disease). Park your Mercedes-Benz.
DOPA
CIRCULATION
DECARBOXYLASE Dopamine 3-OMD
INHIBITOR
– L-DOPA
COMT INHIBITORS
Carbidopa DDC COMT – (peripheral)
BLOOD- Entacapone
BRAIN
BARRIER
L-DOPA
DDC COMT INHIBITOR

(central)
PRESYNAPTIC
TERMINAL FROM THE Dopamine –
Entacapone
SUBSTANTIA NIGRA COMT
3-MT
DOPAC
–
Autoregulatory MAO TYPE B
receptor INHIBITORS
Reuptake
Selegiline
Rasagiline
DOPAMINE +
AVAILABILITY
Amantadine
Dopamine receptors + DOPAMINE AGONISTS

POSTSYNAPTIC
TERMINAL IN
THE STRIATUM Bromocriptine (ergot)
Pramipexole (non-ergot)
Ropinirole (non-ergot)

Levodopa/carbidopa
MECHANISM level of dopamine in brain. Unlike dopamine, l-DOPA can cross blood-brain barrier and is
converted by dopa decarboxylase in the CNS to dopamine. Carbidopa, a peripheral DOPA
decarboxylase inhibitor, is given with l-DOPA to the bioavailability of l-DOPA in the brain and
to limit peripheral side effects.
CLINICAL USE Parkinson disease.
ADVERSE EFFECTS Nausea, hallucinations, postural hypotension from peripheral formation of catecholamines.
Long-term use can lead to dyskinesia following administration (“on-off” phenomenon), akinesia
between doses.
Selegiline, rasagiline
MECHANISM Selectively inhibit MAO-B (metabolize dopamine) dopamine availability.
CLINICAL USE Adjunctive agent to l-DOPA in treatment of Parkinson disease.
ADVERSE EFFECTS May enhance adverse effects of l-DOPA.
Tetrabenazine, reserpine
MECHANISM Inhibit vesicular monoamine transporter (VMAT) dopamine vesicle packaging and release.
CLINICAL USE Huntington chorea, tardive dyskinesia
Riluzole
MECHANISM neuron glutamate excitotoxicity For Lou Gehrig disease, give rilouzole.
CLINICAL USE ALS, survival
Alzheimer disease drugs

Memantine
MECHANISM NMDA receptor antagonist; helps prevent
excitotoxicity (mediated by Ca2+).
ADVERSE EFFECTS Dizziness, confusion, hallucinations.
Donepezil, rivastigmine, galantamine
MECHANISM AChE inhibitors. Dona Riva dances at the gala.
ADVERSE EFFECTS Nausea, dizziness, insomnia.
Anesthetics—general CNS drugs must be lipid soluble (cross the blood-brain barrier) or be actively transported.
principles Drugs with solubility in blood = rapid induction and recovery times.
Drugs with solubility in lipids = potency = 1
MAC
MAC = Minimal Alveolar Concentration (of inhaled anesthetic) required to prevent 50% of
subjects from moving in response to noxious stimulus (eg, skin incision).
Examples: nitrous oxide (N2O) has blood and lipid solubility, and thus fast induction and low
potency. Halothane, propofol, and thiopental, in contrast, have lipid and blood solubility, and
thus high potency and slow induction.

Inhaled anesthetics Desflurane, halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, N2O.

MECHANISM Mechanism unknown.
EFFECTS Myocardial depression, respiratory depression, nausea/emesis, cerebral blood flow ( cerebral
metabolic demand).
ADVERSE EFFECTS Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane,
epileptogenic), expansion of trapped gas in a body cavity (N2O).
Malignant hyperthermia—rare, life-threatening condition in which inhaled anesthetics or
succinylcholine induce fever and severe muscle contractions. Susceptibility is often inherited
as autosomal dominant with variable penetrance. Mutations in voltage-sensitive ryanodine
receptor (RYR1 gene) cause Ca2+ release from sarcoplasmic reticulum. Treatment: dantrolene (a
ryanodine receptor antagonist).
Intravenous anesthetics
AGENT MECHANISM ANESTHESIA USE NOTES
Thiopental Facilitate GABA A (barbiturate). Induction of anesthesia, short cerebral blood flow. High
surgical procedures. lipid solubility. Effect
terminated by rapid
redistribution into tissue and
fat.
Midazolam Facilitate GABA A Procedural sedation (eg, May cause severe postoperative
(benzodiazepine). endoscopy), anesthesia respiratory depression, BP,
induction. anterograde amnesia.
Propofol Potentiates GABA A. Rapid anesthesia induction,
short procedures, ICU
sedation.
Ketamine NMDA receptor antagonist. Dissociative anesthesia. cerebral blood flow.
Sympathomimetic. Emergence reaction
possible with disorientation,
hallucination, vivid dreams.
Local anesthetics Esters—procaine, tetracaine, benzocaine, chloroprocaine.

Amides—lIdocaIne, mepIvacaIne, bupIvacaIne, ropIvacaIne (amIdes have 2 I’s in name).
MECHANISM Block Na+ channels by binding to specific receptors on inner portion of channel. Most effective in
rapidly firing neurons. 3° amine local anesthetics penetrate membrane in uncharged form, then
bind to ion channels as charged form.
Can be given with vasoconstrictors (usually epinephrine) to enhance local action— bleeding,
anesthesia by systemic concentration.
In infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate membrane
effectively need more anesthetic.
Order of nerve blockade: small-diameter fibers > large diameter. Myelinated fibers > unmyelinated
fibers. Overall, size factor predominates over myelination such that small myelinated fibers
> small unmyelinated fibers > large myelinated fibers > large unmyelinated fibers.
Order of loss: (1) pain, (2) temperature, (3) touch, (4) pressure.
CLINICAL USE Minor surgical procedures, spinal anesthesia. If allergic to esters, give amides.
ADVERSE EFFECTS CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension,
arrhythmias (cocaine), methemoglobinemia (benzocaine).

Neuromuscular Muscle paralysis in surgery or mechanical ventilation. Selective for Nm nicotinic receptors at
blocking drugs neuromuscular junction but not autonomic Nn receptors.
Depolarizing Succinylcholine—strong ACh receptor agonist; produces sustained depolarization and prevents
neuromuscular muscle contraction.
blocking drugs Reversal of blockade:
Phase I (prolonged depolarization)—no antidote. Block potentiated by cholinesterase inhibitors.
Phase II (repolarized but blocked; ACh receptors are available, but desensitized)—may be
reversed with cholinesterase inhibitors.
Complications include hypercalcemia, hyperkalemia, malignant hyperthermia.
Nondepolarizing Atracurium, cisatracurium, pancuronium, rocuronium, tubocurarine, vecuronium—competitive
neuromuscular with ACh for receptors.
blocking drugs Reversal of blockade—neostigmine (must be given with atropine or glycopyrrolate to prevent
muscarinic effects such as bradycardia), edrophonium, and other cholinesterase inhibitors.
Dantrolene
MECHANISM Prevents release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle by binding to the
ryanodine receptor.
CLINICAL USE Malignant hyperthermia (a toxicity of inhaled anesthetics and succinylcholine) and neuroleptic
malignant syndrome (a toxicity of antipsychotic drugs).
Baclofen
MECHANISM Skeletal muscle relaxant. GABA B receptor agonist in spinal cord.
CLINICAL USE Muscle spasticity, dystonia, multiple sclerosis.
Cyclobenzaprine
MECHANISM Skeletal muscle relaxant. Acts within CNS.
CLINICAL USE Muscle spasms.
ADVERSE EFFECTS Anticholinergic side effects. Sedation.
Opioid analgesics
MECHANISM Act as agonists at opioid receptors (μ = β-endorphin, δ = enkephalin, κ = dynorphin) to modulate
synaptic transmission—close presynaptic Ca2+ channel, open postsynaptic K+ channels
synaptic transmission. Inhibit release of ACh, norepinephrine, 5-HT, glutamate, substance P.
EFFICACY Full agonist: morphine, heroin, meperidine, methadone, codeine.
Partial agonist: buprenorphine.
Mixed agonist/antagonist: nalbuphine, pentazocine.
Antagonist: naloxone, naltrexone, methylnaltrexone.
CLINICAL USE Moderate to severe or refractory pain, cough suppression (dextromethorphan), diarrhea
(loperamide, diphenoxylate), acute pulmonary edema, maintenance programs for heroin addicts
(methadone, buprenorphine + naloxone).
ADVERSE EFFECTS Nausea, vomiting, pruritus, addiction, respiratory depression, constipation, sphincter of Oddi
spasm, miosis (except meperidine mydriasis), additive CNS depression with other drugs.
Tolerance does not develop to miosis and constipation. Toxicity treated with naloxone (opioid
receptor antagonist) and relapse prevention with naltrexone once detoxified.

Pentazocine
MECHANISM κ-opioid receptor agonist and μ-opioid receptor weak antagonist or partial agonist.
CLINICAL USE Analgesia for moderate to severe pain.
ADVERSE EFFECTS Can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (due to
competition for opioid receptors).
Butorphanol
MECHANISM κ-opioid receptor agonist and μ-opioid receptor partial agonist.
CLINICAL USE Severe pain (eg, migraine, labor). Causes less respiratory depression than full opioid agonists.
ADVERSE EFFECTS Use with full opioid agonist can precipitate withdrawal. Not easily reversed with naloxone.
Tramadol
MECHANISM Very weak opioid agonist; also inhibits 5-HT receptors.
CLINICAL USE Chronic pain.
ADVERSE EFFECTS Similar to opioids. Decreases seizure threshold. Serotonin syndrome.
Glaucoma drugs IOP via amount of aqueous humor (inhibit synthesis/secretion or drainage).
BAD humor may not be Politically Correct.
DRUG CLASS EXAMPLES MECHANISM ADVERSE EFFECTS
β-blockers Timolol, betaxolol, carteolol aqueous humor synthesis No pupillary or vision changes
α-agonists Epinephrine (α1), aqueous humor synthesis via Mydriasis (α1); do not use in
apraclonidine, vasoconstriction (epinephrine) closed-angle glaucoma
brimonidine (α2) aqueous humor synthesis Blurry vision, ocular
(apraclonidine, brimonidine) hyperemia, foreign body
sensation, ocular allergic
reactions, ocular pruritus
Diuretics Acetazolamide aqueous humor synthesis No pupillary or vision changes
via inhibition of carbonic
anhydrase
Prostaglandins Bimatoprost, latanoprost outflow of aqueous humor via Darkens color of iris
(PGF2α) resistance of flow through (browning), eyelash growth
uveoscleral pathway
Cholinomimetics (M3) Direct: pilocarpine, carbachol outflow of aqueous humor via Miosis (contraction of pupillary
Indirect: physostigmine, contraction of ciliary muscle sphincter muscles) and
echothiophate and opening of trabecular cyclospasm (contraction of
meshwork ciliary muscle)
Use pilocarpine in acute angle
closure glaucoma—very
effective at opening meshwork
into canal of Schlemm

536 SEC TION III NEUROLOGY AND SPECIAL SENSES
NOTES
``

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Neurotransmitter changes with disease

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Limbic system Collection of neural structures involved in The famous 5 F’s.

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Cerebral cortex regions

Premotor Central sulcus Somatosensory

Broca area Wernicke area

Homunculus Topographic representation of motor (shown)

regions being more richly innervated and thus

having  cortical representation.

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Cerebral arteries—cortical distribution

Anterior cerebral artery (supplies anteromedial surface)

Middle cerebral artery (supplies lateral surface)

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Posterior inferior Vertebral VA

Superior sagittal sinus

Inferior sagittal sinus

Great cerebral vein of Galen Superior ophthalmic vein

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Ventricular system Lateral ventricles  3rd ventricle via right and

Brain stem—dorsal view (cerebellum removed) Pineal gland—melatonin secretion, circadian

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Cranial nerve and vessel pathways

Anterior Cribriform plate CN I

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Cranial nerve reflexes

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Mastication muscles 3 muscles close jaw: Masseter, teMporalis, M’s Munch.

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Anterior white commissure Lateral

Anterior spinothalamic tract

Lateral corticospinal tract Intermediate horn (sympathetic)

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Spinal tract anatomy Ascending tracts synapse and then cross.

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Diaphragm and gallbladder pain referred to the V2

right shoulder via phrenic nerve

C3, 4, 5 keeps the diaphragm alive

Thumbs up sign on left hand looks like a 6

T4 at the teat pore

having cortical representation.

Ventricular system Lateral ventricles 3rd ventricle via right and

Neurodegenerative in cognitive ability, memory, or function with intact consciousness.

Hydrocephalus CSF volume ventricular dilation +/− ICP.

Conjunctivitis Inflammation of the conjunctiva red eye A .

Horner syndrome Sympathetic denervation of face : PAM is horny (Horner).