Nervioso First Aid

460 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 of developing brain

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 Aqueduct

(mesencephalon)
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 461
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 (fetal AChE in CSF flows through defect into amniotic fluid).
Anencephaly Failure of rostral neuropore to close no forebrain, open calvarium. Clinical findings:
polyhydramnios (no swallowing center in brain).
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.
+/− 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 ).
462 SEC TION III NEUROLOGY AND SPECIAL SENSES NEUROLOGY—EMBRYOLOGY
Posterior fossa malformations

Chiari I malformation Ectopia of cerebellar tonsils (1 structure) > 3–5 mm 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 with cystic enlargement of 4th ventricle (arrow in B ), 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 arrow 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 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 ),
trauma, and tumors.
NEUROLOGY AND SPECIAL SENSES NEUROLOGY—ANATOMY AND PHYSIOLOGY SEC TION III 463
Tongue development 1st and 2nd branchial arches form anterior 2/3 Taste—CN VII, IX, X (solitary nucleus).
Anterior tongue (thus sensation via CN V3, taste via CN VII). Pain—CN V3, IX, X.
Arches 3rd and 4th branchial arches form posterior 1/3 Motor—CN X, XII.
1 and 2 (thus sensation and taste mainly via CN IX,
Sensation extreme posterior via CN X).
via V3
Taste Motor innervation is via CN XII to hyoglossus
via VII
(retracts and depresses tongue), genioglossus
(protrudes tongue), and styloglossus (draws
sides of tongue upward to create a trough for
Sensation
and taste swallowing).
via IX Arches
Motor innervation is via CN X to palatoglossus
3 and 4
Sensation
and taste
(elevates posterior tongue during swallowing).
via X
Posterior tongue
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 Physical support, repair, extracellular K+ buffer, Derived from neuroectoderm. Astrocyte marker:
removal of excess neurotransmitter, component GFAP.
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.
464 SEC TION III NEUROLOGY AND SPECIAL SENSES 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
are high concentrations of Na+ channels.
Synthesis of myelin by oligodendrocytes in
CNS and Schwann cells in PNS.
Schwann cells Each Schwann cell myelinates only 1 PNS axon. May be 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
brain and spinal cord. between arachnoid and pia mater.
Dura mater—thick outer layer closest to Epidural space—a potential space between the
skull. Derived from mesoderm. dura mater and skull containing fat and blood
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 Adenohyophysis
(anterior pituitary) and Neurohypophysis (posterior pituitary) release of hormones produced in
the hyopthalamus, 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 area Hunger. Destruction anorexia, failure If you zap your lateral area, you shrink laterally.
to thrive (infants). Stimulated by ghrelin,
inhibited by leptin.
Ventromedial area Satiety. Destruction (eg, craniopharyngioma) If you zap your ventromedial area, you grow
hyperphagia. Stimulated by leptin. ventrally and medially.
Anterior Cooling, parasympathetic. Anterior nucleus = cool off (cooling,
hypothalamus pArasympathetic). A/C = anterior cooling.
Posterior Heating, sympathetic. Posterior nucleus = get fired up (heating,
hypothalamus sympathetic). 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.
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.
Oral desmopressin (ADH analog) is useful in treatment of bedwetting (sleep enuresis); preferred over
imipramine because of the latter’s adverse effects, although motivational therapy (eg, star chart)
should still be first-line for bedwetting in children.
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
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.
NUCLEUS 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 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.
Papez circuit consists of hippocampus (red
arrows in A ), 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
balance. extremities (Limbs); when injured, propensity
Input: to fall toward injured (ipsilateral) side.
Contralateral cortex via middle cerebellar Medial lesions—involvement of Midline
peduncle. structures (vermal cortex, fastigial nuclei)
Ipsilateral proprioceptive information via and/or flocculonodular lobe truncal ataxia
inferior cerebellar peduncle from spinal (wide-based cerebellar gait), nystagmus, head
cord. tilting. Generally result in bilateral motor
Output: deficits affecting axial and proximal limb
The only output of cerebellar cortex = musculature.
Purkinje cells (always inhibitory) deep
nuclei of cerebellum contralateral cortex
via superior cerebellar peduncle.
Deep nuclei (lateral medial)—Dentate,
Emboliform, Globose, Fastigial (“Don’t Eat
Greasy Foods”).
Basal ganglia Important in voluntary movements and making postural

adjustments.
Receives cortical input, provides negative feedback to cortex to
modulate movement.
Striatum = putamen (motor) + caudate (cognitive). D1-Receptor = D1Rect
Lentiform = putamen + globus pallidus. pathway.
Indirect = Inhibitory.
Input from SNc
Stimulatory
Dopamine
Inhibitory
D1 D2 SNc Substantia nigra pars compacta

GPe Globus pallidus externus
GPi Globus pallidus internus
STN Subthalamic nucleus
Direct Indirect
Motor cortex pathway pathway D1 Dopamine D1 receptor
facilitates inhibits D2 Dopamine D2 receptor
movement movement
From Putamen (striatum)

Thalamus SNc
t
rec
Di
ect
Indir
GPi GPe
STN
Pedunculo-
pontine
nucleus
Spinal
cord
Excitatory pathway—cortical inputs stimulate the striatum, stimulating the release of GABA, which
inhibits GABA release from the GPi, disinhibiting the thalamus via the GPi ( motion).
Inhibitory pathway—cortical inputs stimulate 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
lus
association area scicu
e fa
rcuat
A
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).
Cerebral perfusion CO2

Cerebral blood flow
Cerebral blood flow

pressure ∝ PCO2 until
normal PO2 PCO2 > 90 mm Hg
Normal O2
Hypoxemia increases
cerebral perfusion pressure
only when PO2 < 50 mm Hg
Normal
normal PCO2
50 100 150 40 80 120

Arterial gas pressure (mm Hg) Arterial gas pressure (mm Hg)
Cerebral arteries—cortical distribution
Anterior cerebral artery (supplies anteromedial surface)
Middle cerebral artery (supplies lateral surface)
Posterior cerebral artery (supplies posterior and inferior surfaces)
Watershed zones Between anterior cerebral/middle cerebral, posterior cerebral/middle cerebral arteries. Damage by
severe hypotension upper leg/upper arm weakness, defects in higher-order visual processing.
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 External
P2 ECA carotid PCom
Posterior artery
PCA
cerebral ICA
Common
CCA carotid
artery VA
Superior
SCA Pontine
Brachio-
cerebellar
cephalic
Subclavian
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 dura. Drain blood from cerebral veins (arrow) and
A
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
horn horn
3rd ventricle 4th ventricle via cerebral
aqueduct of Sylvius.
4th ventricle subarachnoid space via: Foramina
Foramina of Luschka = Lateral. of Monro
Foramen of Magendie = Medial. Third Cerebral
ventricle aqueduct
CSF is made by ependymal cells of choroid of Sylvius
plexus; it is reabsorbed by arachnoid
Foramina of Luschka Fourth
granulations and then drains into dural venous
ventricle
sinuses. Foramen of Magendie
Brain stem—ventral
Optic chiasm Olfactory bulb (CN I)
view
Olfactory tract
CN II
Infundibulum
Optic tract
CN III
Mammillary body CN IV (arises dorsally
and immediately
decussates)
Pons CN V
CN VI
Middle cerebellar CN VII
peduncle CN VIII
Pyramid
CN IX
Pyramidal decussation CN X
CN XI
C1 CN XII
4 CN are above pons (I, II, III, IV).

4 CN are in pons (V, VI, VII, VIII).
4 CN are in medulla (IX, X, XI, XII).
4 CN nuclei are medial (III, IV, VI, XII). “Factors of 12, except 1 and 2.”
Brain stem—dorsal Pineal gland—melatonin secretion, circadian Your eyes are above your ears, and the superior
view (cerebellum rhythms. colliculus (visual) is above the inferior
removed) Superior colliculi—conjugate vertical gaze colliculus (auditory).
center.
Inferior colliculi—auditory. Pineal body
Superior colliculi
Inferior colliculi
Superior cerebellar 4th ventricle

peduncles
Middle cerebellar Medulla

peduncles
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) Hypoglossal canal CN XII
Brainstem
Foramen magnum Spinal root of CN XI
Vertebral arteries
Divisions of CNV 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 2/3 of tongue, lacrimation, Both Brother
salivation (submandibular and sublingual glands), eyelid closing
(orbicularis oculi), auditory volume modulation (stapedius)
Vestibulocochlear VIII Hearing, balance Sensory Says
Glossopharyngeal IX Taste and sensation from posterior of tongue, swallowing,
1/3 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) 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 in medial
spinal cord ascend medulla) lemniscus
ipsilaterally in dorsal
columns VPL (thalamus)
sensory cortex
Spinothalamic tract Lateral: pain, Sensory nerve Ipsilateral gray Decussates at
temperature ending (Aδ and C matter (spinal anterior white
Anterior: fibers) bypass cord) commissure
crude touch, pseudounipolar cell ascends
pressure body in dorsal root contralaterally
ganglion enter
spinal cord
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 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 C2—posterior half of the skull. Diaphragm and gallbladder pain referred to the
V1
C3—high turtleneck shirt. right shoulder via phrenic nerve (C3–C5).
C2
V2 C3
C4—low-collar shirt.
V3 C4 C6—includes thumbs. Thumbs up sign on left hand looks like a six for C6.
C5
T1 T4—at the nipple. T4 at the teat pore.
T4 C6 T 7—at the xiphoid process.
T6
T10—at the umbilicus (important for early T10 at the belly butten.
T8 C7
T10
appendicitis pain referral).
C8
C6 S2
T12
L1 C8
L1—at the inguinal ligament. L1 is IL (Inguinal Ligament).
S3 L4—includes the kneecaps. Down on ALL 4’s (L4).
L4
S2, S3, S4—erection and sensation of penile and “S2, 3, 4 keep the penis off the floor.”
anal zones.
L5
NEUROLOGY AND SPECIAL SENSES NEUROLOGY—NEUROPATHOLOGY SEC TION III 481
NEUROLOGY—NEUROPATHOLOGY
Common brain lesions

AREA OF LESION CONSEQUENCE EXAMPLES
Frontal lobe Disinhibition and deficits in concentration,
orientation, judgment; may have reemergence
of primitive reflexes.
Frontal eye fields Eyes look toward lesion.
Paramedian pontine Eyes look away from side of lesion.
reticular formation
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).
Superior colliculus Parinaud syndrome—paralysis of conjugate Stroke, hydrocephalus, pinealoma.
vertical gaze (rostral interstitial nucleus also
involved).
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.
Cerebellar vermis Truncal ataxia, dysarthria. Vermis is centrally located—affects central body.
Degeneration associated with chronic alcohol
use.
482 SEC TION III NEUROLOGY AND SPECIAL SENSES NEUROLOGY—NEUROPATHOLOGY
Ischemic brain Irreversible damage begins after 5 minutes of hypoxia. Most vulnerable: hippocampus, neocortex,
disease/stroke cerebellum, 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 Red neurons Necrosis + Macrophages Reactive gliosis Glial scar
features (eosinophilic neutrophils (microglia) + vascular
cytoplasm proliferation
with
pyknotic
nuclei)
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; 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).
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.
Intracranial hemorrhage
Epidural hematoma Rupture of middle meningeal artery (branch A B
of maxillary artery), often 2° to skull
fracture A involving the pterion (thinnest
area of the lateral skull). Lucid interval. Rapid
expansion 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 E F
hemorrhage an 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. 4–10 days after
hemorrhage, vasospasm (narrowing of blood
vessels) can occur due to blood breakdown
or rebleed 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. Typically occurs in basal ganglia G
and internal capsule (Charcot-Bouchard
microaneurysm of lenticulostriate vessels),
but can also occur in cerebral hemispheres,
brainstem, 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 sensory
cerebral limb. loss—lower limb.
artery
Lenticulo- Striatum, internal capsule. Contralateral paralysis and/or Common location of lacunar
striate sensory loss—face and body. infarcts B , due to hyaline
artery Absence of cortical signs arteriosclerosis 2° to
(eg, neglect, aphasia, visual field unmanaged hypertension.
loss).
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 Vestibular nuclei reflex Nucleus ambiguus effects are
artery Lateral spinothalamic tract, spinal Vomiting, vertigo, nystagmus specific to PICA lesions C .
trigeminal nucleus pain and temperature sensation “Don’t pick a (PICA) horse
from contralateral body, (hoarseness) that can’t eat
ipsilateral face (dysphagia).”
Sympathetic fibers Ipsilateral Horner syndrome Also supplies inferior cerebellar
Inferior cerebellar peduncle Ataxia, dysmetria peduncle (part of cerebellum).
Anterior Lateral pons Lateral pontine syndrome.

inferior Facial nucleus Paralysis of face, lacrimation, Facial nucleus effects are
cerebellar salivation, taste from anterior specific to AICA lesions.
artery 2
⁄3 of tongue “Facial droop means AICA’s
Vestibular nuclei Vomiting, vertigo, nystagmus pooped.”
Spinothalamic tract, spinal pain and temperature sensation Also supplies middle and
trigeminal nucleus from contralateral body, inferior cerebellar peduncles
ipsilateral face (part of cerebellum).
Sympathetic fibers Ipsilateral Horner syndrome
Middle and inferior cerebellar Ataxia, dysmetria
peduncles
Effects of strokes (continued)

ARTERY AREA OF LESION SYMPTOMS NOTES
Basilar artery Pons, medulla, lower midbrain RAS spared, therefore preserved “Locked-in syndrome.”
consciousness
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.
artery
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. Occurs in 10% of stroke
patients.
Aphasia Aphasia—higher-order language deficit (inability to understand/speak/read/write).

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 (berry) Occurs at bifurcations in the circle of Willis. Most common site is junction of ACom and
aneurysm 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 on 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 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). 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. Often (febrile seizures are not epilepsy).
preceded by seizure aura; can secondarily Status epilepticus—continuous (> 5–30 min)
generalize. Types: or recurring seizures that may result in brain
Simple partial (consciousness intact)— injury.
motor, sensory, autonomic, psychic Causes of seizures by age:
Complex partial (impaired consciousness) Children—genetic, infection (febrile),
Generalized seizures Diffuse. Types: trauma, congenital, metabolic
Absence (petit mal)—3 Hz spike-and-wave Adults—tumor, trauma, stroke, infection
discharges, no postictal confusion, blank Elderly—stroke, tumor, trauma, metabolic,
stare infection
Myoclonic—quick, repetitive jerks
Tonic-clonic (grand mal)—alternating
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; Repetitive brief headaches. Acute: sumatriptan, 100% O2
repetitive Excruciating periorbital Prophylaxis: verapamil
pain with lacrimation and
rhinorrhea. May present with
Horner syndrome.
Tension Bilateral > 30 min Steady pain. No photophobia Analgesics, NSAIDs,
(typically 4–6 or phonophobia. No aura. acetaminophen;
hr); constant 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, calcium channel
vessels (release of substance blockers, amitriptyline,
P, calcitonin gene-related topiramate, valproate.
peptide, vasoactive peptides). POUND–Pulsatile, One-day
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 that
lasts (typically) for < 1 minute (note: first-line therapy is carbamazepine).

Movement disorders
DISORDER PRESENTATION CHARACTERISTIC LESION NOTES
Akathisia Restlessness and intense urge Can be seen with neuroleptic
to move use or in Parkinson disease.
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 Sydenham chorea seen in acute
rheumatic fever.
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 distal Substantia nigra (Parkinson Occurs at rest; “pill-rolling
appendages (most noticeable disease) tremor” of Parkinson disease.
in hands); tremor alleviated by When you park your car, it is
intentional movement at rest.
Neurodegenerative in cognitive ability, memory, or function with intact consciousness.

disorders
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 can cause
parkinsonian symptoms.
Huntington disease Autosomal dominant trinucleotide (CAG)n Atrophy of caudate and putamen with ex vacuo
repeat disorder on chromosome 4. Symptoms ventriculomegaly.
manifest between ages 20 and 50: chorea, dopamine, GABA, ACh in brain. Neuronal
athetosis, aggression, depression, dementia death via NMDA-R binding and glutamate
(sometimes initially mistaken for substance excitotoxicity.
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.
Associated with the following altered proteins: Senile plaques D in gray matter: extracellular
ApoE2: risk of sporadic form β-amyloid core; may cause amyloid angiopathy
ApoE4: risk of sporadic form intracranial hemorrhage; Aβ (amyloid-β)
APP, presenilin-1, presenilin-2: familial synthesized by cleaving amyloid precursor
forms (10%) with earlier onset protein (APP).
ACh Neurofibrillary tangles E : intracellular,
hyperphosphorylated tau protein = insoluble
cytoskeletal elements; number of tangles
correlates with degree with dementia.
Frontotemporal Early changes in personality and behavior Frontotemporal lobe degeneration F .
dementia (Pick (behavioral variant), or aphasia (primary Inclusions of hyperphosphorylated tau (round
disease) progressive aphasia). Pick bodies G ) or ubiquitinated TDP-43.
May have associated movement disorders
(eg, parkinsonism, ALS-like UMN/LMN
degeneration).
Lewy body dementia Dementia and visual hallucinations Intracellular Lewy bodies A primarily in cortex.
(“haLewycinations”) parkinsonian features
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”). Prions (PrPc PrPsc sheet [β-pleated sheet
Commonly see periodic sharp waves on EEG resistant to proteases]) H .
and 14-3-3 protein in CSF.
A B C D
E F G H
Idiopathic intracranial ICP with no apparent cause on imaging (eg, hydrocephalus, obstruction of CSF outflow). Risk
hypertension factors include female gender, obesity, vitamin A excess, tetracycline, danazol.
(pseudotumor cerebri) Findings: headache, diplopia (usually from CN VI palsy), no change in mental status. Papilledema
seen on fundoscopy. Lumbar puncture reveals opening pressure and provides headache relief.
Treatment: weight loss, acetazolamide, topiramate, invasive procedures for refractory cases
(eg, repeat lumbar puncture, CSF shunt placement, optic nerve sheath fenestration surgery).
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, ataxia, and cognitive dysfunction (sometimes reversible). “Wet,
wobbly, and wacky.” Characteristic magnetic gait (feet appear stuck to floor).
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 decreased brain tissue and neuronal
ventriculomegaly atrophy (eg, Alzheimer disease, advanced HIV, Pick disease, Huntington disease). ICP is normal;
triad is not seen.
A B C
Osmotic demyelination Acute paralysis, dysarthria, dysphagia, diplopia, Correcting serum Na+ too fast:
syndrome (central loss of consciousness. Can cause “locked-in “From low to high, your pons will die”
pontine myelinolysis) syndrome.” Massive axonal demyelination in (osmotic demyelination syndrome)
A
pontine white matter A 2° to osmotic changes. “From high to low, your brain will blow”
Commonly iatrogenic, caused by overly rapid (cerebral edema/herniation)
correction of hyponatremia. In contrast,
correcting hypernatremia too quickly results in
cerebral edema/herniation.
Multiple sclerosis Autoimmune inflammation and demyelination of CNS (brain and spinal cord). Patients can
present with optic neuritis (sudden loss of vision resulting in Marcus Gunn pupils), INO,
hemiparesis, hemisensory symptoms, bladder/bowel dysfunction. 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. Neck flexion may precipitate sensation of electric shock running
down spine (Lhermitte phenomenon).
Charcot triad of MS is a SIN:
Scanning speech
Intention tremor (also Incontinence and Internuclear ophthalmoplegia)
Nystagmus
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) with
preservation of axons. Multiple white matter lesions disseminated in space and time.
TREATMENT 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).
Acute inflammatory Most common subtype of Guillain-Barré Associated with infections (eg, Campylobacter
demyelinating syndrome. Autoimmune condition that jejuni, viral) autoimmune attack of
polyradiculopathy destroys Schwann cells inflammation and peripheral myelin due to molecular mimicry,
demyelination of peripheral nerves and motor inoculations, and stress, but no definitive link
fibers. Results in symmetric ascending muscle to pathogens.
weakness/paralysis and depressed tendon Respiratory support is critical until recovery.
reflexes beginning in lower extremities. Facial Additional treatment: plasmapheresis, IV
paralysis in 50% of cases. May see autonomic immunoglobulins. No role for steroids.
dysregulation (eg, cardiac irregularities,
hypertension, hypotension) or sensory
abnormalities. Almost all patients survive; the
majority recover completely after weeks to
months.
CSF protein with normal cell count
(albuminocytologic dissociation). protein
may cause papilledema.
Other demyelinating and dysmyelinating diseases

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 (HMSN). Group of progressive hereditary
disease nerve 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.
Krabbe disease Autosomal recessive lysosomal storage disease due to deficiency of galactocerebrosidase. Buildup
of galactocerebroside and psychosine destroys myelin sheath. Findings: peripheral neuropathy,
developmental delay, optic atrophy, globoid cells.
Metachromatic Autosomal recessive lysosomal storage disease, most commonly due to arylsulfatase A deficiency.
leukodystrophy Buildup of sulfatides impaired production and destruction of myelin sheath. Findings: central
and peripheral demyelination with ataxia, dementia.
Progressive multifocal Demyelination of CNS A due to destruction of oligodendrocytes. Seen in 2–4% of AIDS patients
leukoencephalopathy (reactivation of latent JC virus infection). Rapidly progressive, usually fatal. risk associated with
A
natalizumab, rituximab.
Adrenoleukodystrophy X-linked genetic disorder typically affecting males. Disrupts metabolism of very-long-chain fatty
acids excessive buildup in nervous system, adrenal gland, testes. Progressive disease that can
lead to long-term coma/death and adrenal gland crisis.
Neurocutaneous disorders
Sturge-Weber Congenital, noninherited (sporadic), developmental anomaly of neural crest derivatives due to
syndrome somatic mosaicism for an activating mutation in one copy of the GNAQ gene. Affects small
(encephalotrigeminal (capillary-sized) blood vessels port-wine stain of the face A (nevus flammeus, a non-neoplastic
angiomatosis) “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/TSC2 mutation on chromosome 16. 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 Mutation in NF1 tumor suppressor gene on chromosome 17 (17 letters in “von Recklinghausen”),
type I (von which normally codes for neurofibromin, a negative regulator of RAS. Autosomal dominant,
Recklinghausen 100% penetrance. Café-au-lait spots F , cutaneous neurofibromas G , optic gliomas,
disease) 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. Characterized
disease 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 Common, highly malignant 1° brain tumor with Astrocyte origin, GFAP ⊕. “Pseudopalisading”
multiforme (grade IV ~ 1-year median survival. Found in cerebral pleomorphic tumor cells B border central
astrocytoma) hemispheres A . Can cross corpus callosum areas of necrosis and hemorrhage.
(“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 1° brain tumor. 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 or Hyperplasia of only one type of endocrine cells
hyperfunctioning. Most commonly found in pituitary (ie, lactotroph, gonadotroph,
from lactotrophs (prolactinoma) I somatotroph, corticotroph).
hyperprolactinemia; less commonly
adenoma of somatotrophs (GH) acromegaly/
gigantism; corticotrophs (ACTH) Cushing’s
disease. Rarely, adenoma of thyrotrophs (TSH)
and gonadotroph (FSH, LH). Bitemporal
hemianopia due to pressure on 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 ⊕.
but can be along any peripheral nerve. Often
localized to CN VIII in internal acoustic
meatus → 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

Pilocytic (low-grade) Usually well circumscribed. In children, Glial cell origin, GFAP ⊕. Rosenthal
astrocytoma most often found in posterior fossa A (eg, fibers—eosinophilic, corkscrew fibers B .
cerebellum). May be supratentorial. Benign; Cystic + solid (gross).
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. 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 rosettes 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 Calcification is common G H . Cholesterol
(both cause bitemporal hemianopia). 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 Cingulate (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. Compresses
cerebelli ipsilateral CN III (blown pupil, “down-and-
Kernohan out” gaze), ipsilateral PCA (contralateral
Duret notch
hemorrhage homonymous hemianopia with macular
sparing), contralateral crus cerebri at the
Kernohan notch (ipsilateral paresis; a “false
localization” sign).
Cerebellar 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
Poliomyelitis and Werdnig-Hoffmann Congenital degeneration of anterior horns of spinal
disease cord. LMN lesions only. “Floppy baby” with marked
hypotonia and tongue fasciculations. Infantile type
has median age of death of 7 months. Autosomal
recessive inheritance.
Poliomyelitis asymmetric weakness.
Werdnig-Hoffmann disease symmetric weakness.
Amyotrophic lateral sclerosis Combined UMN and LMN deficits with no sensory
or bowel/bladder deficits (due to loss of cortical and
spinal cord motor neurons, respectively).
Can be caused by defect in superoxide dismutase 1.
Commonly presents with asymmetric limb weakness
(hands/feet), fasciculations, eventual atrophy. Fatal.
Commonly known as Lou Gehrig disease.
Treatment: riluzole.
Posterior spinal 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. Presents
with UMN deficit below the lesion (corticospinal
tract), LMN deficit at the level of the lesion (anterior
horn), and loss of pain and temperature sensation
Anterior spinal artery
below 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).
Associated with Charcot joints, shooting pain, Argyll
Robertson pupils.
Exam will demonstrate absence of DTRs and
⊕ Romberg sign.
Syringomyelia Syrinx expands and damages anterior white

commissure of spinothalamic tract (2nd-order
neurons) bilateral loss of pain and temperature
sensation in cape-like distribution; seen with Chiari
I malformation; can expand and 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 Unilateral symptoms including radicular pain, absent

knee and ankle reflex, loss of bladder and anal
sphincter control. Can cause saddle anesthesia.
Treatment: emergent surgery and steroids.
Due to compression of spinal roots from L2 and
below, often caused by intravertebral disk herniation
or tumors.
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 Ipsilateral loss of all sensation at level of
lesion
Ipsilateral LMN signs (eg, flaccid paralysis) at Level of lesion
level of lesion
Loss of
Ipsilateral UMN signs below level of lesion sensation
(due to corticospinal tract damage) LMN signs
Lesion Ipsilateral loss of proprioception, vibration,
light (2-point discrimination) touch, and
tactile sense below level of lesion (due to
dorsal column damage). UMN signs
Impaired pain,
Contralateral pain, temperature, and crude Impaired temperature,
(non-discriminative) touch below level of proprioception, and crude touch
lesion (due to spinothalamic tract damage) vibration, light sensation
touch, and
If lesion occurs above T1, patient may present tactile sense
with ipsilateral Horner syndrome due to
damage of oculosympathetic pathway.
Friedreich ataxia Autosomal recessive trinucleotide repeat Friedreich is Fratastic (frataxin): he’s your
A
disorder (GAA)n on chromosome 9 in gene favorite frat brother, always staggering and
that encodes frataxin (iron binding protein). falling but has a sweet, big heart.
Leads to impairment in mitochondrial Ataxic GAAit.
functioning. Degeneration of multiple spinal
cord tracts muscle weakness and loss
of DTRs, vibratory sense, proprioception.
Staggering gait, frequent falling, nystagmus,
dysarthria, pes cavus, hammer toes, diabetes
mellitus, hypertrophic cardiomyopathy
(cause of death). Presents in childhood with
kyphoscoliosis A .
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

Upper motor neuron Destruction of motor cortex or connection
lesion between motor cortex and facial nucleus in
pons contralateral paralysis of lower muscles
of facial expression. Forehead is spared due to
its bilateral UMN innervation.
Lower motor neuron Destruction of facial nucleus or CN VII
lesion anywhere along its course ipsilateral
A
paralysis of upper and lower muscles of
facial expression A , hyperacusis, loss of taste
sensation to anterior tongue.
When idiopathic (most common), facial nerve
palsy is called Bell palsy. May also be caused
by Lyme disease, herpes simplex, herpes
zoster (Ramsay Hunt syndrome), sarcoidosis,
tumors (eg, parotid gland), diabetes mellitus.
Treatment is corticosteroids, acyclovir. Most
patients gradually recover function.
NEUROLOGY AND SPECIAL SENSES NEUROLOGY—OTOLOGY SEC TION III 503
NEUROLOGY—OTOLOGY
Auditory physiology
Outer ear Visible portion of ear (pinna), includes auditory canal and eardrum. Transfers sound waves via
vibration of eardrum.
Middle ear Air-filled space with three bones called the ossicles (malleus, incus, stapes). Ossicles conduct and
amplify sound from eardrum 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

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

Noise-induced Damage to stereociliated cells in organ of Corti. Loss of high-frequency hearing first. Sudden
extremely loud noises can produce hearing loss due to tympanic membrane rupture.
Presbycusis Aging-related 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.
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, benign paroxysmal positional vertigo). Positional testing delayed horizontal
nystagmus.
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. Positional
testing immediate nystagmus in any direction; may change directions. Focal neurologic
findings.
504 SEC TION III NEUROLOGY AND SPECIAL SENSES NEUROLOGY—OPHTHALMOLOGY
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
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.
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).
NEUROLOGY AND SPECIAL SENSES NEUROLOGY—OPHTHALMOLOGY SEC TION III 505
Cataract Painless, often bilateral, opacification of lens A , often resulting in vision. Acquired risk factors:
A 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
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
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 Posterior 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 the 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 forward 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. Do not give epinephrine because of its mydriatic effect.
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, 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.
Retinal vein occlusion Blockage of central or branch retinal vein due to compression from nearby arterial atherosclerosis.
A
Retinal hemorrhage and venous engorgement (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 at
occlusion fovea (center of macula) A . Evaluate for embolic source (eg, carotid artery atherosclerosis, cardiac
A
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
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 contract bilaterally Nasal
retina
pupillae
muscles
(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.
Marcus Gunn pupil Afferent pupillary defect—due to optic nerve damage or severe retinal injury. bilateral pupillary
constriction when light is shone in affected eye relative to unaffected eye. Tested with “swinging
flashlight test.”
Horner syndrome Sympathetic denervation of face : PAM is horny (Horner).

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

Associated with lesion of spinal cord above of forehead
T1 (eg, Brown-Séquard syndrome, late-stage To smooth muscle of eyelid

To pupillary dilator
syringomyelia) or of the stellate ganglion Internal
carotid To sweat glands of face
alongside the spinal cord (eg, Pancoast tumor). artery
External carotid artery
Any interruption results in Horner syndrome. C2
Third neuron
First neuron
Superior cervical ganglion
Synapse is
in lateral horn T1
Second neuron
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 superior oblique abducts, intorts, and
rectus rectus
muscle muscle depresses while adducted.
Lateral
Inferior Inferior rectus
oblique rectus muscle
muscle muscle
Inferior Inferior
rectus oblique
muscle muscle
To test each muscle, ask patient to move his/ Obliques go Opposite (left SO and IO tested
her eye in the path diagrammed to the right, with patient looking right).
from neutral position toward the muscle being IOU: IO tested looking Up.
tested.
CN III, IV, VI palsies

CN III damage CN III has both motor (central) and A
parasympathetic (peripheral) components.
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 B
contralateral gaze B (problems going down
stairs, may present with compensatory head tilt
in the opposite direction).
CN VI damage Medially directed eye that cannot abduct C . 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
(right temporal lesion, MCA) chiasm

2 4
Lateral 3
5. Left lower quadrantanopia geniculate
Meyer
loop
(right parietal lesion, MCA) body
(temporal 4
Dorsal optic 5 lobe)
6. Left hemianopia with macular sparing radiation
(parietal 5
(PCA infarct) lobe)
3 (6 if
7. Central scotoma (eg, macular degeneration) Visual PCA infarct) 6
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 occasionally V2 plus postganglionic sympathetic pupillary fibers en route
to orbit all pas s 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), a conjugate horizontal gaze palsy. Lack
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
514 SEC TION III NEUROLOGY AND SPECIAL SENSES NEUROLOGY—PHARMACOLOGY
NEUROLOGY—PHARMACOLOGY
Epilepsy drugs
GENERALIZED
PARTIAL (FOCAL)
TONIC-CLONIC
EPILEPTICUS
ABSENCE
STATUS
MECHANISM SIDE EFFECTS NOTES
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
Benzodiazepines ** GABA A action Sedation, tolerance, Also for eclampsia seizures (1st
(eg, diazepam, ✓ dependence, respiratory line is MgSO4)
lorazepam, depression
midazolam)
Phenobarbital ✓ ✓ GABA A action Sedation, tolerance, 1st line in neonates
dependence, induction
of cytochrome P-450,
cardiorespiratory depression
Phenytoin, ✓ * *** Blocks Na+ channels; zero- Neurologic: nystagmus, diplopia, ataxia, sedation, peripheral
fosphenytoin ✓ ✓ order kinetics neuropathy. Dermatologic: hirsutism, Stevens-Johnson
syndrome, gingival hyperplasia, DRESS syndrome.
Musculoskeletal: osteopenia, SLE-like syndrome. Hematologic:
megaloblastic anemia. Reproductive: teratogenesis (fetal
hydantoin syndrome). Other: cytochrome P-450 induction
Carbamazepine * ✓ Blocks Na+ channels Diplopia, ataxia, blood 1st line for trigeminal neuralgia
✓ dyscrasias (agranulocytosis,
aplastic anemia), liver
toxicity, teratogenesis,
induction of cytochrome
P-450, SIADH, Stevens-
Johnson syndrome
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 by irreversibly Permanent visual loss (black
inhibiting GABA box warning)
transaminase
Gabapentin ✓ Primarily inhibits high-voltage- Sedation, ataxia Also used for peripheral
activated Ca2+ channels; neuropathy, postherpetic
designed as GABA analog neuralgia
Topiramate ✓ ✓ Blocks Na+ channels, GABA Sedation, mental dulling, Also used for migraine
action kidney stones, weight loss, prevention
glaucoma
Lamotrigine ✓ ✓ ✓ Blocks voltage-gated Na+ Stevens-Johnson syndrome
channels, inhibits the release (must be titrated slowly)
of glutamate
Levetiracetam ✓ ✓ Unknown; may modulate Fatigue, drowsiness,
GABA and glutamate release headache, neuropsychiatric
symptoms (eg, personality
changes)
Tiagabine ✓ GABA by inhibiting reuptake
* = 1st line; ** = 1st line for acute; *** = 1st line for prophylaxis.
NEUROLOGY AND SPECIAL SENSES NEUROLOGY—PHARMACOLOGY SEC TION III 515
Barbiturates Phenobarbital, pentobarbital, thiopental, secobarbital.

MECHANISM Facilitate GABA A action by duration of Cl− channel opening, thus neuron firing (barbidurates
duration). Contraindicated in porphyria.
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).
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). metabolized Outside The Liver
CLINICAL USE Anxiety, spasticity, status epilepticus (lorazepam
and diazepam), eclampsia, 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. “All 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
activation; prevent vasoactive peptide release; head.
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
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, tolcapone—prevent peripheral l-DOPA degradation to 3-O-methyldopa (3-OMD)
by inhibiting COMT.
Prevent dopamine Agents act centrally (post-BBB) to inhibit breakdown of dopamine.
breakdown Selegiline—blocks conversion of dopamine into DOPAC by selectively inhibiting MAO-B.
Tolcapone—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
DECARBOXYLASE CIRCULATION
Dopamine 3-OMD
INHIBITOR
– L-DOPA
COMT INHIBITORS
Carbidopa DDC COMT – (peripheral)
BLOOD- Entacapone
BRAIN Tolcapone
BARRIER
L-DOPA
DDC COMT INHIBITOR

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

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 Arrhythmias 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.
Huntington disease Tetrabenazine and reserpine—inhibit vesicular monoamine transporter (VMAT) dopamine
drugs vesicle packaging and release.
Haloperidol—D2 receptor antagonist.
Riluzole Treatment for ALS that modestly survival For Lou Gehrig disease, give rilouzole.
by glutamate excitotoxicity via an unclear
mechanism.
Alzheimer disease drugs

Memantine
MECHANISM NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+).
ADVERSE EFFECTS Dizziness, confusion, hallucinations.
Donepezil, galantamine, rivastigmine, tacrine
MECHANISM AChE inhibitors.
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, in contrast, has 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
cause Ca2+ release from sarcoplasmic reticulum. Treatment: dantrolene (a ryanodine receptor
antagonist).
Intravenous The Mighty King Proposes to Oprah.

anesthetics
Barbiturates High potency, high lipid solubility, rapid entry into brain. Used for induction of anesthesia and
(Thiopental) short surgical procedures. Effect terminated by rapid redistribution into tissue and fat. cerebral
blood flow.
Benzodiazepines Used for endoscopy; used adjunctively with gaseous anesthetics and narcotics. May cause severe
(Midazolam) postoperative respiratory depression, BP (treat overdose with flumazenil), anterograde amnesia.
Arylcyclohexylamines PCP analogs that act as dissociative anesthetics. Block NMDA receptors. Cardiovascular
(Ketamine) stimulants. Cause disorientation, hallucination, unpleasant dreams. cerebral blood flow.
Propofol Used for sedation in ICU, rapid anesthesia induction, short procedures. Less postoperative nausea
than thiopental. Potentiates GABA A.
Opioids Morphine, fentanyl used with other CNS depressants during general anesthesia.
Local anesthetics Esters—procaine, cocaine, tetracaine, benzocaine.

Amides—lIdocaIne, mepIvacaIne, bupIvacaIne (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
muscle contraction.
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 Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium—competitive
antagonists—compete with ACh for receptors.
Reversal of blockade—neostigmine (must be given with atropine 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 and neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).
Baclofen
MECHANISM Activates GABA B receptors at spinal cord level, inducing skeletal muscle relaxation.
CLINICAL USE Muscle spasms (eg, acute low back pain), multiple sclerosis.
Cyclobenzaprine
MECHANISM Centrally acting skeletal muscle relaxant. Structurally related to TCAs, similar anticholinergic side
effects.
CLINICAL USE Muscle spasms.
Opioid analgesics Morphine, oxycodone, fentanyl, codeine, loperamide, methadone, meperidine, dextromethorphan,
diphenoxylate, pentazocine.
MECHANISM Act as agonists at opioid receptors (μ = β-endorphin, δ = enkephalin, κ = dynorphin) to modulate
synaptic transmission—open K+ channels, close Ca2+ channels synaptic transmission. Inhibit
release of ACh, norepinephrine, 5-HT, glutamate, substance P.
CLINICAL USE 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, 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 antagonist (competition
for opioid receptors).
Butorphanol
MECHANISM κ-opioid receptor agonist and μ-opioid receptor partial agonist; produces analgesia.
CLINICAL USE Severe pain (eg, migraine, labor). Causes less respiratory depression than full opioid agonists.
ADVERSE EFFECTS Can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition for
opioid receptors). Overdose not easily reversed with naloxone.
Tramadol
MECHANISM Very weak opioid agonist; also inhibits 5-HT and norepinephrine reuptake (works on multiple
neurotransmitters—“tram it all” in with tramadol).
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).
DRUG MECHANISM ADVERSE EFFECTS
α-agonists
Epinephrine (α1), aqueous humor synthesis via vasoconstriction Mydriasis (α1); do not use in closed-angle
brimonidine (α2) (epinephrine) glaucoma
aqueous humor synthesis (brimonidine) Blurry vision, ocular hyperemia, foreign body
sensation, ocular allergic reactions, ocular
pruritus
β-blockers
Timolol, betaxolol, aqueous humor synthesis No pupillary or vision changes
carteolol
Diuretics
Acetazolamide aqueous humor synthesis via inhibition of No pupillary or vision changes
carbonic anhydrase
Cholinomimetics (M3)
Direct (pilocarpine, outflow of aqueous humor via contraction Miosis (contraction of pupillary sphincter
carbachol) of ciliary muscle and opening of trabecular muscles) and cyclospasm (contraction of ciliary
Indirect meshwork muscle)
(physostigmine, Use pilocarpine in emergencies—very effective
echothiophate) at opening meshwork into canal of Schlemm
Prostaglandin
Bimatoprost, outflow of aqueous humor via resistance of Darkens color of iris (browning), eyelash growth
latanoprost (PGF2α) flow through uveoscleral pathway

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460 SEC TION III NEUROLOGY AND SPECIAL SENSES NEUROLOGY—EMBRYOLOGY

Regional specification of developing brain

Telencephalon Cerebral Lateral

Forebrain Diencephalon Thalamus, Third

Midbrain Mesencephalon Midbrain Aqueduct

Pons Upper part of

Normal Spina bifida occulta Meningocele Meningomyelocele

Posterior fossa malformations

NEUROLOGY—ANATOMY AND PHYSIOLOGY

Microglia Phagocytic scavenger cells of CNS HIV-infected microglia fuse to form

Myelin sheath Node of Ranvier

Oligodendrocytes Myelinates axons of neurons in CNS. Each Derived from neuroectoderm.

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

Neurotransmitter changes with disease

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

Basal ganglia Important in voluntary movements and making postural

D1 D2 SNc Substantia nigra pars compacta

From Putamen (striatum)

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.

Cerebral perfusion CO2

Cerebral blood flow

50 100 150 40 80 120

Cerebral arteries—cortical distribution

Anterior cerebral artery (supplies anteromedial surface)

Middle cerebral artery (supplies lateral surface)

Posterior cerebral artery (supplies posterior and inferior surfaces)

Posterior inferior Vertebral VA

Superior sagittal sinus

Inferior sagittal sinus

Great cerebral vein of Galen Superior ophthalmic vein

4 CN are above pons (I, II, III, IV).

Superior cerebellar 4th ventricle

Middle cerebellar Medulla

Cranial nerve and vessel pathways

Cranial nerve reflexes

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

Anterior white commissure Lateral

Anterior spinothalamic tract

Lateral corticospinal tract Intermediate horn (sympathetic)

Spinal tract anatomy Ascending tracts synapse and then cross.

Common brain lesions

Subdural hematoma Rupture of bridging veins. Can be acute C D

Anterior Lateral pons Lateral pontine syndrome.

Effects of strokes (continued)

Aphasia Aphasia—higher-order language deficit (inability to understand/speak/read/write).

Aneurysms Abnormal dilation of an artery due to weakening of vessel wall.

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

lasts (typically) for < 1 minute (note: first-line therapy is carbamazepine).

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

Neurodegenerative disorders (continued)

Hydrocephalus CSF volume ventricular dilation +/− ICP.

Other demyelinating and dysmyelinating diseases

Adult primary brain tumors

Adult primary brain tumors (continued)

Childhood primary brain tumors

Motor neuron signs

Spinal cord lesions

Tabes dorsalis Caused by 3° syphilis. Results from degeneration