Neurohistology:

 The nervous system is composed of 2 components:

o neurons (signal-transmitting cells)
o glial cells (supporting non-neuronal ➝ modulate transmissions at synapse or myelinate nerves)
 Neurons:
o Permanent cells—do not divide in adulthood.
o Neuron markers ➝ neurofilament protein, synaptophysin.
o Each neuron ➝ broken into dendrites (receive input), cell bodies, and axons (send output).
o Nissl stain ➝ stains cell body & dendrites b/c have RER & polyribosome (Nissl body appear dark)
 Chromatolysis:
o Axonal injury ➝ cell body reacts by  protein synthesis to repair the damage.
o Characterized by:
 Round cellular swelling
 Displacement of the nucleus to the periphery
 Dispersion of Nissl substance throughout cytoplasm*
o Wallerian degeneration: distal to inj. ➝ axon & myelin sheath disintegrate w mp removing debris
o Axonal retraction:
 Proximal to injury ➝ axon retracts & cell body sprouts new protrusions that grow toward other neurons for
potential reinnervation.
 Serves as preparation for axonal regeneration and functional recovery.
 Glial Cells: (Gliosis is proliferation and hypertrophy of glial cells ➝ astrocytes change if CNS injury)
o PNS glial cell type (Schwann cells)
o CNS glial cell types (Maeyo ➝ microglia, astrocytes, ependymal cells, oligodendrocytes)
 Schwann cells:
o derived from neural crest & are similar to oligodendrocytes.
o myelinate neurons of PNS (one cell myelinates one neuron).
o Ds ➝ Guillain-Barré, Charcot-Marie-Tooth ds, vestibular schwannoma (acoustic neuromas).
 Myelin:
o It wraps & insulates axons:
  membrane capacitance,  membrane resistance
  space (length) constant,  time constant
o  conduction velocity of signals ➝ transmitted down axons ➝ saltatory conduction of action potential at nodes of
Ranvier, where there are high concentrations of Na+ channels.
o In CNS (including CN II) ➝ myelin is synthesized by oligodendrocytes.
o In PNS (including CN III-XII) ➝ myelin is synthesized by Schwann cells.
 Microglia:
o derived from mesoderm (NOT readily discernible by Nissl stain)
o Phagocytic scavenger cells of CNS (i.e., resident macrophages).
o Brain damage/infection ➝ release of inflammatory mediators (e.g., nitric oxide, glutamate).
o HIV- associated dementia ➝ HIV-infected microglia fuse to form multinucleated giant cells.
 Astrocytes (MC)
o Contain GFAP marker (used in brain cancer like astrocytoma and glioblastoma)
o Functions
 Physical support, a component of BBB
 repair, removal of excess NT, glycogen fuel reserve buffer
 Responds to neural injury (reactive gliosis)
 Ependymal Cells:
o derived from neuroectoderm.
o Ciliated simple columnar glial cells lining ventricles & central canal of spinal cord.
o Apical surfaces ➝ covered with cilia (circulates CSF) and microvilli (helps with CSF absorption).
o Specialized ependymal cells (choroid plexus in ventricles) produce CSF.
o Diseases ➝ ependymomas & syringomyelia.
 Oligodendrocytes:
o derived from neuroectoderm.
o Oligodendrocytes myelinate axons of neurons in CNS (one cell myelinates multiple neurons).
o Predominant type of glial cell in white matter.
 o “Fried egg” appearance histologically.
o Injured in ➝ MS, progressive multifocal leukoencephalopathy (PML), leukodystrophies.
Peripheral Nerves
 Endoneurium (endo = inner)—supportive CT that ensheathes & supports individual myelinated nerve fibers ➝ affected in
GBS
 Perineurium (blood-nerve permeability barrier)—surrounds a fascicle of nerve fibers (peri = around).
 Epineurium (epi = outer)—dense connective tissue that surrounds the entire nerve (fascicles and blood vessels).

Neurophysiology:
 Neuron Action Potential:
o Resting membrane potential:
 membrane is more permeable to K than Na at rest ➝ Voltage-gated Na & K channels are closed
o Membrane depolarization: Na+ activation gate opens ➝ Na+ flows inward.
o Membrane repolarization:
 Na+ inactivation gate closes at peak potential, thus stopping Na+ inflow.
 K+ activation gate opens ➝ K+ flows outward.
o Membrane hyperpolarization:
 K+ activation gates are slow to close ➝ excess K+ efflux and brief period of hyperpolarization.
 Voltage-gated Na+ channels switch back to resting state.
 Na+/K+ pump restores ions concentration.
 Educational Objective:
o Kinesin is a microtubule-associated, ATP-powered motor protein that facilitates anterograde transport of NT-
containing secretory vesicles down axons to synaptic terminals.
 Neurotransmitters:
o Excitatory NT ➝ glutamate, aspartate, nitric oxide
o Inhibitory NT ➝ glycine, GABA, serotonin (5-HT)
o Both ➝ acetylcholine (ACh), dopamine (DA), norepinephrine (NA)
NT Site  
ACh Basal nucleus of Meynert (Forebrain) Parkinson’s 1. Alzheimer’s
Neuromuscular junction 2. Huntington’s
DA Midbrain 1. 1. Depression
- SNc (substantia nigra pars compacta) Schizophrenia 2. Parkinson’s
- Ventral tegmentum 2. Huntington’s
NA Locus coeruleus (pons) Anxiety Depression
Serotonin Raphe nucleus (pons, medulla) Serotonin 1. Anxiety
syndrome 2. Depression
3. Parkinson’s
GABA Nucleus accumbens (basal ganglia) - 1. Anxiety; 2. Huntington’s
 Sensory Receptors
o Free Nerve Endings
 Types ➝ A—fast, myelinated fibers; C—slow, unmyelinated fibers
 Location ➝ All tissues (numerous in skin) except cartilage & eye lens
 Senses ➝ pain, temperature
o Fast-adapting Receptors
 Meissner corpuscles
 Large, myelinated fibres; adapt quickly
 Location ➝ Glabrous (hairless) skin
 Senses ➝ Dynamic fine/light touch, low-frequency vibration, skin indentation
 Pacinian corpuscles
 Large, myelinated fibres; adapt quickly
 Location ➝ Deep skin layers, ligaments, joints
 Senses ➝ High-frequency vibration, pressure
o Slow-adapting Receptors
 Merkel disks
 Large, myelinated fibres; adapt slowly
 Location ➝ Fingertips, superficial skin
 Senses ➝ Pressure, deep static touch (e.g., sharps, edges)
  Ruffini corpuscles
 Large, myelinated fibers intertwined among collagen fiber bundles; adapt slowly
 Location ➝ Fingertips, joints
 Senses ➝ Stretch, joint angle change

 Muscle Receptors
o Muscle spindles:
 Nerve roots for reflexes ➝ ankle (S1-2), patellar (L3-4), biceps (C5-6), triceps (C6-8)
 Spindles in intrafusal fibers run parallel to contractile muscle fibers/extrafusal fibers
 Detects change in length of skeletal muscle fibers.
 Myotactic reflex
 hit patellar tendon to stretch it ➝ pulls on muscle spindle ➝ sends info to spinal cord
 stimulates knee extensor to contract & inhibits flexors ➝ causing knee to jerk
o Golgi Tendon Organ:
 Present at jxn of tendon & muscle fibers (tendons arranged perpendicular to extrafusal fibers)
 Detects force of contraction via afferent nerves & provides autogenic inhibition reflex
 Causes muscle relaxation before a tendon can be torn thus weightlifters drop weight before it’s too late
 Sleep Cycle (EEG)
o  REM & N3 sleep ➝ Alcohol, benzodiazepines (useful for night terrors and sleepwalking), barbiturates, NA
o 2 stages ➝ rapid-eye movement (REM) and non-REM regulated by circadian rhythm.
o Circadian rhythm
 driven by suprachiasmatic nucleus (SCN) of hypothalamus.
 controls nocturnal release of ACTH, prolactin, melatonin, norepinephrine
 SCN (regulated by environment e.g., light) ➝ norepinephrine release ➝ pineal gland ➝  melatonin
 Cerebral Perfusion Pressure (CPP)
o Relies on tight autoregulation primarily driven by Pco2 (Po2 also modulates perfusion in severe hypoxia).
 if Po2 < 50 mm Hg ➝ Hypoxemia increases CPP.
 if Pco2 < 90 mm Hg ➝ CPP is directly proportional to Pco2.
o Also relies on a pressure gradient between mean arterial pressure (MAP) & ICP
o CPP = MAP – ICP ➝ maintained between 50 – 150 mmHg. (Note: MAP = DP +1/3 Pulse Pressure)
o  CPP
 If  BP or  ICP (traumatic brain injury or cerebral edema 2° to stroke)
 If CPP = 0, there is no cerebral perfusion ➝ brain death (coma, absent brainstem reflexes, apnea).
o So, in response to  ICP
 Cushing reflex ➝ HT, bradycardia, respiratory depression
 Therapeutic hyperventilation ➝  pCO2 ➝ cerebral vasoconstriction ➝  cerebral blood flow ➝ ICP
 Relieved by hypertonic saline, mannitol, or craniotomy.
Neuroanatomy
 Meninges
o 3 membranes that surround & protect the brain and spinal cord:
 Dura mater – thick outer layer closest to skull. Derived from mesoderm.
 Arachnoid mater – middle layer, contains weblike connections. Derived from neural crest.
 Pia mater – thin, fibrous inner layer that firmly adheres to brain & spinal cord. Derived from neural crest.
o Spaces
 Subarachnoid space ➝ CSF flows in subarachnoid space, located between arachnoid and pia mater.
 Epidural space
 potential space between dura mater & skull/vertebral column containing fat and blood vessels.
 Site of blood collection associated with middle meningeal artery injury.

 Blood Brain Barrier (BBB)

o Prevents circulating blood substances e.g., bacteria, drugs from reaching CSF/ CNS.
o Formed by 4 structures:
 Tight junctions between non-fenestrated capillary endothelial cells
 Basement membrane
 Pericytes; Astrocyte foot processes
o Glucose & amino acids ➝ cross slowly by carrier-mediated transport mechanisms.
o Nonpolar/lipid-soluble substances ➝ cross rapidly via diffusion.
o Neurosecretory products ➝ can enter circulation (e.g., neurohypophysis-ADH release).
o Circumventricular organs with fenestrated capillaries & no BBB allow molecules in blood to affect brain function
E.g.,
 Area postrema – vomiting after chemotherapy;
 OVLT [organum vasculosum lamina terminalis] – osmoreceptors
o BBB disruption
 Stroke ➝ vasogenic edema.
 Hyperosmolar agents (e.g., mannitol) can disrupt BBB ➝  permeability of medications.
 Vomiting Center
o Coordinated by nucleus tractus solitarius (NTS) in medulla, which receives info. from
 chemoreceptor trigger zone (located in area postrema (pronounce "puke"-strema) in 4th ventricle)
 GI tract (via vagus nerve)
 vestibular system, CNS
o CTZ & adjacent vomiting center nuclei receive input through 5 major receptors:
 histamine (H1), muscarinic (M1), neurokinin (NK-1), dopamine (D2), and serotonin (5-HT3).
 5-HT3, D2, and NK-1 antagonists ➝ used to treat chemotherapy-induced vomiting.
 H1 and M1 antagonists ➝ treat motion sickness.
 H1 antagonists ➝ treat hyperemesis gravidarum.
 Cerebral Cortex
o Frontal lobe
 1o motor cortex
 Premotor area (plans movement)
 frontal eye fields (involved in voluntary eye movements)
 Broca’s area (left) ➝ motor aspect of speech production is linked here.
 Executive functions (cognition, planning, decision making, error correction, troubleshooting)
o Parietal lobe ➝ 1o somatosensory area & somatosensory associated cortex.
o Occipital lobe ➝ processes & integrates visual info.
o Temporal lobe
 1o auditory cortex (auditory perception)
 Wernicke’ (associative auditory cortex) ➝ written & spoken language is understood
 Arcuate fasciculus aids in language processing by connecting the Broca’s and Wernicke’s areas
 Cortical Homunculus
o Topographic representation of motor (frontal lobe) & sensory areas (parietal lobe) in cerebral cortex.
 o Hand, face, lip have  cortical representation b/c  neurons are devoted to fine motor control of hand compared to
hip
o Middle cerebral artery supplies lateral cerebral hemisphere ➝ occlusion causes upper extremities & lower face
deficit
o Anterior cerebral artery supplies medial cerebral hemisphere ➝ occlusion causes LL & trunk neurologic deficits
 Cerebral Circulation
o Provided by internal carotid arteries & vertebral arteries (left & right)
o Anterior circulation is provided by internal carotid arteries ➝ branch into anterior and middle cerebral arteries.
 ACA
 Supplies the anteromedial surfaces
 Includes frontal, parietal, basal ganglia (anterior), internal capsule, medial motor homunculus
 MCA
 Supplies the lateral surfaces
 Ant. & inf. temporal, insular cortices, lateral surfaces of hemispheres, basal ganglia (deep
branches)
o posterior circulation
 Provided by vertebral arteries
 Fuse to form basilar artery (supplies brainstem and cerebellum)
 Branches into PCA ➝ supplies posterior & inferior surfaces, primarily formed by occipital lobe.
o Circle of Willis
 Anastomoses between ant. & post. blood supplies allow for collateral (backup) circulation
 Anterior communicating artery ➝ connects left & right anterior cerebral arteries.
 Posterior communicating arteries ➝ interconnects internal carotid with posterior circulation.
o Watershed Zones
 Cortical border zones ➝ occur b/w ACA & MCA + PCA & MCA (blue areas in A)
 Internal border zones ➝ occur b/w superficial & deep vascular territories of middle cerebral artery (red
areas)
 Dural Venous Sinuses
o Large venous channels that run through periosteal & meningeal layers of dura mater.
o Drain blood from cerebral veins & receive CSF from arachnoid granulations.
o Venous drainage of brain includes superficial (superior sagittal sinus) & deep subdivisions (inferior sagittal sinus)
o They connect at confluence of sinuses before bifurcating into two transverse sinuses.
o Transverse sinuses travel lat. & inf. in S-shape to form sigmoid sinuses ➝ Empty into internal jugular veins.
o Venous sinus thrombosis*
 CF of  ICP (e.g., headache, seizures, papilledema, focal neurologic deficits) ➝ venous hemorrhage
 Associated with hypercoagulable states (e.g., pregnancy, OCP use, factor V Leiden)
 Cavernous Sinus
o Collection of venous sinuses on either side of pituitary.
o Blood from eye & superficial cortex ➝ cavernous sinus ➝ internal jugular vein.
o CNs III, IV, V1, V2, VI, postganglionic sympathetic pupillary fibers en route to orbit all pass-through cavernous
sinus.
o Cavernous portion of internal carotid artery is also here.
o Cavernous sinus syndrome
 variable ophthalmoplegia (e.g., CN III & CN VI),
  corneal sensation
 Horner syndrome
  maxillary sensation
 2° to pituitary tumor mass effect,
 carotid-cavernous fistula/cavernous sinus thrombosis related to infection (spread d/t NO valve in Dural
sinus)
 Basal Ganglia
o Subcortical structure is a group of nuclei whose function is to modulate voluntary movements & adjusting posture
o Receives cortical input, provides negative feedback to cortex to modulate movement.
o Consists of following:
 Striatum = putamen (deals with motor) + Caudate nucleus (deals with cognitive).
 Lentiform = putamen + globus pallidus externa (GPe = lat. ext. segment) & interna (GPi = medial internal)
 Subthalamic nucleus ➝ only portion of pathway to produce excitatory NT glutamate.
 Substantia nigra ➝ pars compacta (SNc; DA-producing) & pars reticulata (SNr)
o Signal
 Starts at primary motor cortex (precentral gyrus) ➝ glutamate stimulates GABA release from striatum
 Direct (excitatory) pathway (initiates movements)
 inhibits GABA release from GPi
 Normally, GPi tonically inhibits thalamus ➝ so direct pathway inhibits inhibition of thalamus.
 Therefore, activating the Thalamus ( thalamic output to motor cortex) ➝  motion.
 Indirect (inhibitory) pathway (terminates movements)
 inhibits GABA release from GPe
 Normally, GPe inhibits sub-thalamic nucleus (STN) ➝ so inhibition of STN is turned off.
 STN input (via glutamate) stimulates GABA release from GPi
 Normally, GPi inhibits the thalamus so  GPi activity leads to  thalamic inhibition ➝  motion.
 Dopamine ➝  motion
 via substantia nigra pars compacta (SNc) mediates the excitatory and inhibitory signals
 Dopamine binding to D1 receptors ➝ stimulates the direct pathway
 Dopamine binding to D2 receptors ➝ inhibit indirect (inhibitory) pathway
o Basal ganglia pathology ➝ leads to movement disorders (Wilson’s, tardive dyskinesia, Parkinson, Huntington)
 Dopaminergic Pathways
o Altered by drugs (anti-psychotics) and movement disorders (Parkinson disease)
 MRI: cisterna magna (4), 4 ventricle (5), tentorium cerebelli (7), cerebral
aqueduct (8)

 Thalamus (functions like a switchboard) ➝ relays sensory information (ascending) to the cortex except olfaction.
Nuclei Input Senses Destination
Ventral anterior nuclei & Basal ganglia Motor Motor cortex (frontal lobe)
ventral lateral nuclei Cerebellum
Ventral posterolateral nucleus Spinothalamic pathway Vibration (T. Pain) 1° somatosensory cortex
(VPL) Dorsal columns/medial lemniscus Temperature (Parietal lobe)
Light touch
Pain, pressure,
proprioception (conscious)
Ventral posteromedial nucleus Trigeminal pathway Face sensation 1° somatosensory cortex
(VPM) Gustatory pathway Taste (Parietal lobe)
Medial geniculate nucleus Superior olive & Hearing (medial = music) 1° auditory cortex (temporal)
(MG) inferior colliculus of tectum
Lateral geniculate nucleus CN II, optic chiasm, optic tract Vision (lateral = light) 1° visual cortex (occipital
lobe)
Other nuclei Anterior thalamic nuclei (A)
Pulvinar (Pul)
Dorsomedial nucleus ➝ associated with Korsakoff syndrome
 Hypothalamus
o Maintains homeostasis by
 regulating Thirst and water balance,
 controls Adenohypophysis (anterior pituitary)
 Neurohypophysis (posterior pituitary) release of hormones produced in hypothalamus
 regulating Hunger, Autonomic nervous system, Temperature, Sexual urges (TAN HATS)
o Inputs (areas not protected by BBB)
 OVLT (senses change in osmolarity),
 area postrema in dorsal medulla (responds to emetics)

Nucleus Function Destruction

Anterior (i.e., cooler) Deals with parasympathetic & cooling Leads to hyperthermia (hypothalamic stroke)
Posterior (i.e., heater) Deals with sympathetic & heating Leads to poikilothermic (cold-blooded) individual
Lateral (i.e., lean) Deals with hunger & thirst Anorexia in adults
stimulated by grehlin & inhibited by leptin Failure to thrive in infants
Ventromedial (i.e., massive) Deals with satiety ➝ stimulated by leptin Leads to hyperphagia (e.g., craniopharyngioma)
 Suprachiasmatic nucleus (i.e., sleep to be charismatic) ➝ plays role in circadian rhythm
 Supraoptic & paraventricular nuclei
o Synthesize ADH and oxytocin, respectively (SAD POX: Supraoptic = ADH, Para = Oxytocin)
o ADH & oxytocin are carried by neurophysins down axons to posterior pituitary, where these hormones are stored
and released.
 Preoptic nucleus
o Releases GnRH ➝ thermoregulation, sexual behavior.
o Failure of GnRH-producing neurons to migrate from olfactory pit ➝ Kallmann syndrome.
 MRI: lateral ventricle (4), 3rd ventricle (5)

 Limbic System
o Collection of neural structures involved in emotion, long-term memory, olfaction, behavior modulation, ANS fxn.
o Responsible for feeding, fleeing, fighting, feeling, fucking.
o Consists of
 Hippocampus (red arrows in A)
 Amygdalae, entorhinal cortex
 Cingulate gyrus (yellow arrows in A)
 mammillary bodies, ant. thalamic nuclei
 Ventricular System
o CSF is made by choroid plexuses located in lateral, third, & fourth ventricles.
 Travels to subarachnoid space via foramina of Luschka and Magendie, then
 reabsorbed by arachnoid granulations then drains into dural venous sinuses.
o CSF starts in
 2 lateral ventricles & moves into 3rd ventricle via interventricular foramina of Monro
 Flows into 4th ventricle via cerebral aqueduct of Sylvius.
 Flows into cisterns of subarachnoid space via 3 small foramina
 1 median aperture ➝ foramen of Magendie
 2 lateral apertures ➝ foramina of Luschka
 Then, flows down spinal cord around cauda equina or around superior sagittal sinus.

 Cerebellum
o Functions
 Modulates movement & aids in coordination and balance
 Ipsilateral (unconscious) proprioceptive info. via inferior cerebellar peduncle from spinal cord
o 4 Deep nuclei (from lateral to medial) ➝ dentate, emboliform, globose, fastigial (‘don’t eat greasy foods’)
o Cerebellar input
 Inferior cerebellar peduncle receives ipsilateral proprioception input
 Medial cerebellar peduncle receives contralateral cortical input
o Cerebellar output: Cerebellar cortex sends signals to deep nuclei ➝ sup. cerebellar peduncle ➝ contralateral cortex
o Lateral lesions: affect voluntary movement of extremities (lateral structures) ➝ falls toward injured (ipsilateral)
side.
o Medial lesions: (e.g., vermis, fastigial nuclei, flocculonodular lobe)
  Truncal ataxia (wide-based cerebellar gait), nystagmus, head tilting.
 Bilateral motor deficits occur ➝ affects axial & proximal limb musculature (medial structures)
o Tests: rapid alternating movements (pronation/ supination), finger-to-nose, heel-to-shin, gait, intention tremor.
 Brainstem (medulla, pons, midbrain)
o Pineal gland—melatonin secretion, circadian rhythms.
o Superior colliculi—direct eye movements to stimuli (noise/movements) or objects of interest.
o Inferior colliculi—auditory.
o Cranial Nerve Nuclei (‘2, 2, 4, 4’)
 Located in tegmentum portion of brainstem (between dorsal and ventral portions):
 2 CNs emerge above brainstem—CNs I, II
 Midbrain—nuclei of CN III, IV (IV arises dorsally & immediately decussates)
 Pons—nuclei of CN V, VI, VII, VIII
 Medulla—nuclei of CN IX, X, XII
 Spinal cord—nucleus of CN XI
 Sulcus limitans separates the cranial nerve nuclei into
 Nerve
Table 1: Cranial Medial nuclei (CNs III, IV, VI, XII) – motor (basal plate)
Reflexes Table 2: Vagal nuclei
 Lateral nuclei (rest except CN I, II) – sensory (alar plate)
 Anterior cranial fossa: (through ethmoid) Cribriform plate ➝ CN I (nasal fracture causes temporary or permanent anosmia)
 Middle cranial fossa (through sphenoid bone)
o Optic canal ➝ CN II, ophthalmic artery and central retinal vein.
o Superior orbital fissure ➝ CN III, IV, VI, V1, ophthalmic vein, sympathetic fibers
o Foramen rotundum ➝ CN V2
o Foramen ovale ➝ CN V3
o Foramen spinosum ➝ middle meningeal A., branch of internal maxillary artery (head trauma ➝ epidural
hematoma)
 Posterior cranial fossa (through temporal or occipital bone)
o Internal auditory meatus ➝ CN VII, VIII (Schwannoma grows which causes hearing loss)
o Jugular foramen
 CN IX, X, XI,
 Jugular vein (Lumierre’s syndrome—thrombophlebitis of internal jugular vein caused by head & neck inf.)
o Foramen magnum
 brainstem, vertebral arteries
 CN XI spinal roots (begins outside skull, enters skull via foramen megnum, exits via jugular foramen)
o Hypoglossal canal ➝ CN XII
 Cavernous Sinus
o A collection of veins within skull located lateral to pituitary gland & superior to sphenoid sinus.
o It drains blood from ophthalmic vein & superficial cortical veins into internal jugular vein.
o “O TOM CAT” structures run through the sinus:
 All nerves pass through superior orbital fissure except CN V2 (exits via foramen rotundum)
 Oculomotor nerve (CN III),
 Trochlear nerve (CN IV), Ophthalmic nerve (CN V1), Maxillary nerve (CN V2)
 Carotid artery (internal), Abducens nerve (CN VI), Trochlear N. (repeat)
o Important
 Abducens nerve & carotid artery run through middle of sinus
 Other structures run along the lateral walls
o Cavernous sinus thrombosis
 blood clot in cavernous sinus due to inf. spreading into sinus
 Symptoms
 visual changes, exophthalmos (enlarged sinus pushes eye)
 headache, cranial nerve palsies ➝ MC affected is abducens (VI)
 Mastication Muscles
o 3 muscles close jaw ➝ masseter, temporalis, medial pterygoid.
o 1 muscle protrudes jaw ➝ Lateral pterygoid
o All are innervated by mandibular branch of trigeminal nerve (CN V3)
 Spinal Nerves
o 31 pairs of spinal nerves ➝ 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal.
o Nerves C1–C7 exit above corresponding vertebrae (e.g., C3 exits above the 3rd cervical vertebra).
o C8 spinal nerve exits below C7 and above T1.
 o All other nerves exit below (e.g., L2 exits below the 2nd lumbar vertebra).
 Spinal Cord (Lower Extent)
o In adults ➝ spinal cord ends at lower border of L1–L2 vertebrae.
o Subarachnoid space (which contains the CSF) extends to lower border of S2 vertebra.
o Lumbar puncture
 At L3–L4 or L4–L5 (level of cauda equina) for CSF.
 Keep spinal needle between L3–L5 ➝ to keep the cord alive.
o Needle passes through:
 Skin, Fascia & fat
 Supraspinous & interspinous ligament
 Ligamentum flavum
 Epidural space (epidural anesthesia needle stops here)
 Dura mater, Arachnoid mater, Subarachnoid space (CSF collection occurs here)
 Spinal Cord Tracts
o Spinothalamic tract & Dorsal column (ascending tracts) synapse & then cross.
o Corticospinal tract (descending tract) crosses & then synapses.
o lateral corticospinal, lateral spinothalamic tract ➝ Legs (lumbosacral) are lateral
o Dorsal column ➝ organized with arms outside & legs inside
Brain Lesions
 Eyes
o Frontal eye fields lesion (e.g., MCA stroke) ➝ eyes look away from side of hemiplegia + towards side of lesion
o PPRF lesion (AKA para-abducens nucleus) ➝ eyes look towards side of hemiplegia + away side of lesion
o Medial longitudinal fasciculus lesion (e.g., multiple sclerosis has internuclear ophthalmoplegia)
 impaired adduction of ipsilateral eye
 nystagmus with abduction of contralateral eye
 Frontal lobe syndrome (prefrontal cortex lesion)
o disinhibition, hyperphagia, impulsivity, loss of empathy,
o impaired executive function, akinetic mutism.
o Seen in frontotemporal dementia.
 Dominant parietal cortex lesion: Gerstmann syndrome—agraphia, acalculia, finger agnosia, left-right disorientation
 Non-dominant parietal lesion: Hemispatial neglect syndrome—agnosia of the contralateral side of the world.
 Subcortical
o Basal ganglia lesion (Parkinson, Huntington’s) ➝ Tremor at rest, chorea, athetosis.
o Subthalamic nucleus ➝ contralat. unilat. hemiballismus (high amplitude flinging, flailing movement; Rx:
haloperidol)
 Limbic
o Bilateral lesion of hippocampus (Alzheimer disease) ➝ anterograde amnesia (no new memory formation).
o Bilateral lesions of mammillary bodies
 Wernicke-Korsakoff (thiamine def.) ➝ Wernicke’s encephalopathy (Acute) + Korsakoff syndrome
(chronic)
 Wernicke’s encephalopathy (alcohol) ➝ nystagmus, ophthalmoplegia, gait ataxia, global confusion
 Korsakoff syndrome ➝ amnesia (anterograde+retrograde), confabulation (false memory), personality
change
o Bilateral lesions of amygdala (Klüver-Bucy syndrome)
 disinhibition causes hyperorality, hyperphagia, hypersexuality.
 Seen in HSV-1 encephalitis.
 Midbrain
o Dorsal midbrain lesion ➝ Parinaud syndrome (often due to pineal gland tumors).
o Reticular activating system lesion ➝ Reduced levels of arousal and wakefulness, coma.
 Cerebellar hemisphere
o Intention tremor, limb ataxia, loss of balance; damage to cerebellum ➝ ipsilateral deficits; fall toward side of lesion.
o Cerebellar hemispheres are laterally located—affect lateral limbs.
 Cerebellar vermis
o Degeneration asso. with chronic alcohol use ➝ truncal ataxia (wide-based, drunken sailor gait), nystagmus,
dysarthria
o Vermis is centrally located—affects central body.
Neuroembryology
 Neural development
o Notochord induces overlying ectoderm to differentiate into neuroectoderm and form neural plate.
o Notochord becomes nucleus pulposus of intervertebral disc in adults.
o Neural plate invaginates to form neural crest cells (forms PNS) & neural tube (runs along cranial-caudal axis).
o Neural tube
 Hollow lumen forms the ventricles + Walls forms CNS system tissue
 Lateral walls are divided into alar and basal plates (have same orientation as spinal cord)
 Alar plate (dorsal): sensory; induced by bone morphogenetic proteins (BMPs)
 Basal plate (ventral): motor; induced by sonic hedgehog (SHH)
 Regionalization of Neural Tube
o Prosencephalon (forebrain) ➝ differentiates into Telencephalon & Diencephalon
o Mesencephalon (midbrain) ➝ differentiate into mesencephalon (wall forms midbrain + cavity forms central
aqueduct)
o Rhombencephalon (hindbrain) ➝ differentiates into metencephalon, myelencephalon
 CNS & PNS Origins
o Neuroepithelia in neural tube—CNS neurons, CNS glial cells (astrocytes, oligodendrocytes, ependymal cells).
o Neural crest
 PNS neurons ➝ dorsal root ganglia, autonomic ganglia (sympathetic, parasympathetic, enteric)
 PNS glial cells (Schwann cells, satellite cells), adrenal medulla.
o Mesoderm—microglia (like macrophages).

Cerebral Aqueduct Stenosis

 Congenital stenosis of cerebral aqueduct of sylvius (connects 3-4 th ventricles) ➝ causes CSF accumulation in ventricules
space
 MC cause of hydrocephalus in newborns
 CSF is produced by choroid plexus lining the ventricles.
 Presents with enlarging head circumference due to dilation of ventricles (cranial suture lines are not fused)

Neural Tube Defects

 Definition:
o Arise from incomplete closure of neural tube ➝ associated with diabetes & low folate levels during pregnancy.
o Neuropores fail to fuse by 4th week of development ➝ persistent connection between amniotic cavity & spinal
canal.
  Investigations:
o  alpha-fetoprotein (AFP) in amniotic fluid & maternal serum (except spina bifida occulta = normal AFP)
o  acetylcholinesterase (AChE) in amniotic fluid is a confirmatory test.
 Spina bifida occulta:
o Failure of caudal neuropore to close but no herniation + intact dura (Usually seen at lower vertebral levels)
o Associated with tuft of hair or skin dimple at level of bony defect.
 Spina bifida:
o Caudal neuropore ➝ fails to close post. vertebral arch ➝ vertebral defect (cystic protrusion of underlying tissue)
 Meningocele ➝ Meninges (but no neural tissue) herniate through bony defect.
 Myelomeningocele ➝ Meninges & neural tissue (spinal cord, cauda equina) herniate through bony defect.
 Myeloschisis: (AKA rachischisis) ➝ Exposed, unfused neural tissue without skin/meningeal covering.
 Anencephaly:
o Failure of rostral neuropore to close ➝ no forebrain, open calvarium (absence of skull and brain)
 Maternal polyhydramnios (no swallowing center in brain ➝ impaired fetal swallowing of amniotic fluid)
 'Frog-like' appearance of fetus

Brain Malformation (NOT compatible with post-natal life; survivors are disabled)
 Holoprosencephaly
o Failure of forebrain (prosencephalon) to divide into 2 cerebral hemispheres; Associated with SHH mutations.
o Developmental field defect occurs at weeks 3–4 of development.
o Seen in Patau syndrome (trisomy 13), fetal alcohol syndrome.
o Presents with midline defects:
 mono-ventricle (A), fused basal ganglia (* in A),
 cleft lip/palate, hypotelorism, cyclopia, proboscis.
  risk for pituitary dysfunction (e.g., diabetes insipidus).
 Lissencephaly
o Failure of neuronal migration
 smooth brain surface that lacks sulci and gyri.
 Associated with microcephaly, facial anomalies, hydrocephalus.

Posterior Fossa Malformations

 Dandy-Walker Malformation
o Congenital failure of cerebellar vermis to develop (agenesis of cerebellar vermis)
o Presents as cystic enlargement of 4th ventricle that fills enlarged posterior fossa with NO cerebellum.
o Associated with non-communicating hydrocephalus, spina bifida.
 Arnold-Chiari Malformation (Type I)
o Ectopia of cerebellar tonsils inferior to foramen magnum (1 structure) associated w spinal cavitations
(syringomyelia)
o Manifests as
 asymptomatic in childhood
 headaches and cerebellar symptoms in adulthood
  Arnold-Chiari Malformation (Type II)
o Downward displacement of cerebellum (vermis & tonsils) and medulla (2 structures) through foramen magnum
o Manifests as
 Non-communicating hydrocephalus due to CSF obstruction
 Associated with myelomeningocele (usually lumbosacral).
 More severe than Chiari I ➝ presents early in life with dysphagia, stridor, apnea, limb weakness.

Spinal Cord Lesions

 Syringomyelia
o Cystic degeneration of spinal cord usually on C8-T1 ➝ cystic cavity (syrinx) w/in central canal of spinal cord
o acquired causes include trauma and tumors.
o Most common location cervical > thoracic >> lumbar. Syrinx = tube, as in “syringe.”
o Associated with
 Chiari I malformation (red arrow in A shows low-lying cerebellar tonsils)
 scoliosis and other congenital malformations
o Initially
 Fiber’s crossing in ant. white commissure of spinothalamic tract is damaged first ➝ thus bilateral,
symmetrical loss of pain & temperature in upper extremities in ‘cape like’ distribution
 Spares dorsal column pathway ➝ fine touch and position is preserved
o Later
 Damage to LMN of anterior horn ➝ Muscle atrophy and weakness ( muscle tone & reflexes)
 Damage to lateral horn of hypothalamospinal tract ➝ Horner syndrome with ptosis, miosis, anhidrosis
 Poliomyelitis
o Damage to anterior motor horn due to poliovirus infection
o Presents with LMN signs
 flaccid paralysis with muscle atrophy,
 fasciculations, weakness with decreased muscle tone,
 impaired reflexes,
 Babinski sign -ve (down-going toes)
 Werdnig-Hoffman disease (death after birth)
o Inherited degeneration of anterior motor horn; autosomal recessive ➝ Presents as "floppy baby”
 Amyotrophic Lateral Sclerosis (ALS)
o Most cases are sporadic, arising in middle age adults.
o Zinc-copper superoxide dismutase mutation (SOD1) is present in familial cases ➝ leads to free radical inj. in
neurons
o Degenerative disorder of UMN & LMN of corticospinal tract
 Atrophy & weakness of hands (early sign) ➝ Lack of sensory impairment distinguishes ALS from
syringomyelia
 Anterior motor horn degeneration leads to LMN signs (same as above)
 Lateral corticospinal tract degeneration leads to UMN signs
 spastic paralysis with hyperreflexia
  muscle tone
 Babinski sign +
 Friedreich Ataxia (autosomal recessive)
o Degenerative ds of cerebellum & spinal cord d/t expansion of unstable trinucleotide repeat (GAA) in frataxin gene
o Frataxin is essential for mitochondrial iron regulation ➝ loss results in iron buildup with free radical damage.
o Associated with hypertrophic cardiomyopathy
 o Presents in early childhood ➝ pts are wheelchair bound in few years.
 Degeneration of cerebellum leads to ataxia.
 Degeneration of multiple spinal cord tracts leads to
 loss of vibratory sense & proprioception,
 muscle weakness in lower extremities,
 loss of deep tendon reflexes.

Tongue Development (Pharyngeal Arches)

 1st pharyngeal arch ➝ forms ant. 2/3 of tongue (sensation via CN V3, taste via CN VII).
 3rd & 4th pharyngeal arches ➝ forms post. 1/3 of tongue (sensation & taste mainly via CN IX, extreme posterior via CN X).
 Motor innervation is via CN X to palatoglossus (elevates posterior tongue during swallowing).
 Motor innervation is via CN XII to Figure 1: Syringomyelia
o hyoglossus ➝ retracts and depresses tongue
o genioglossus ➝ protrudes tongue
o styloglossus ➝ draws sides upward to create trough for swallowing
 Taste—CN VII, IX, X (solitary nucleus).
 Pain—CN V3, IX, X.
 Motor—CN X, XII.
Cerebral Edema
 Fluid accumulation in brain parenchyma leads to  ICP (Cushing’s triad/reflex; Shock index = HR/SBP)
 Cytotoxic edema
o intracellular fluid accumulation due to osmotic shift (e.g., Na+/K+-ATPase dysfunction ➝ intracellular Na+)
o Caused by ischemia (early), hyperammonemia, SIADH.
 Vasogenic edema
o extracellular fluid accumulation due to disruption of BBB ( permeability).
o Caused by ischemia (late), trauma, hemorrhage, inflammation, tumors.
Stroke
 Irreversible neuronal injury begins after 5 minutes of hypoxia.
 Most vulnerable: (“stroked hippo need pure water”)
o hippocampus (CA1 region),
o Pyramidal cells of neocortex
o Purkinje cells of cerebellum
o watershed areas (most distal artery infarct)
 Stroke Principles: contralateral symptoms & UMN signs (FAST)
 Stroke Imaging:
o Non-contrast CT to detect ischemic changes within 6–24 hr & exclude hemorrhage (before tPA is given).
o Diffusion-weighted MRI detects ischemia within 3–30 min.
 Ischemic Stroke
o Acute vessel blockage leads to blood flow disruption and subsequent ischemia ➝ infarction ➝ liquefactive necrosis
o Hypoxic ➝ due to systemic hypoperfusion or hypoxemia tends to affect watershed areas (MC during CV surgery)
o Thrombotic ➝ clot forms directly at site of infarction over a ruptured atherosclerotic plaque (commonly in MCA)
(A)
o Embolic
 Embolus from another part of body obstructs vessel & affect multiple vascular territories.
 E.g., AFib, carotid A. stenosis, DVT w patent foramen ovale (paradoxical embolism), infective
endocarditis
o Lacunar infarct / stroke ➝ small, deep-penetrating vessels like lenticulostriate arteries (branch of MCA)
o Transient Ischemic Attack
 Brief, reversible episode of focal neurologic dysfxn w/o acute infarction (MRI negative),
 Caused by focal ischemia (e.g., embolus, small vessel stenosis) ➝ majority resolving in < 15 minutes.
 Presents with amaurosis fugax (transient visual loss) due to retinal artery emboli from carotid artery disease

o Treatment:
 tPA if within 3-4.5 hr of onset & no risk of hemorrhage ➝ &/or thrombectomy if large artery occlusion
 Medical therapy to  risk (aspirin, clopidogrel)
  Rx conditions that  risk (Afib, carotid artery stenosis)
 Optimum control of BP, blood sugars, lipids; smoking cessation
 Ischemic Stroke CF
o Anterior cerebral artery (ACA)
 Lesion in motor and sensory cortices supplying lower limb (NOT face)
 Contralateral paralysis (hemiplegia) & sensory loss of lower limb, urinary incontinence (weak, numb leg)
o Middle cerebral artery (MCA)
 Lesions in
 Motor and sensory cortices supplying upper limb and face (A)
 Temporal lobe (Wernicke area)
 Frontal lobe (Broca area)
 Symptoms (Stroke scale ➝ FAST)
 Contralateral paralysis & sensory loss of upper limb and lower face
 Hemineglect if non-dominant hemisphere occlusion (usually right lobe)
 Aphasia if dominant hemisphere (usually left lobe)
a. Left superior (frontal) ➝ Broca’s aphasia
b. Left inferior (temporal) ➝ Wernicke’s aphasia asso. w rt. Sup. quadrant visual field
defect
o Lenticulostriate artery
 Lesion in striatum, internal capsule
 MC in lacunar infarct (B) d/t microatheroma & hyaline arteriosclerosis (lipohyalinosis) 2° to unmanaged
HT
 Contralateral paralysis of LL, UL, face (NO cortical signs e.g., neglect, aphasia, visual field loss)
o Posterior cerebral artery (PCA) area of lesion is occipital lobe (C) with following symptoms:
 Contralateral hemianopia with macular sparing
 Alexia without agraphia (dominant hemisphere, extending to splenium of corpus callosum)
 Prosopagnosia (nondominant hemisphere)
o Basilar artery
 Ocular cranial nerve nuclei, PPRF ➝ loss of horizontal eye movement (NOT vertical)
 Pons, medulla, lower midbrain ➝ RAS spared thus preserved consciousness (Locked-in syndrome)
 Corticospinal and corticobulbar tracts
 Quadriplegia
 loss of voluntary facial (except blinking), mouth, and tongue movements.
o Anterior inferior cerebellar artery (AICA)
 Inner ear ➝ ipsilateral sensorineural deafness, vertigo (supplied by labyrinthine A, branch of AICA)
 Facial nerve nuclei* (lateral pons thus lateral pontine syndrome)
 Paralysis of face (LMN lesion vs UMN lesion in cortical stroke)
  lacrimation, salivation, taste from anterior 2/3 of tongue
 Vestibular nuclei ➝ Vomiting, vertigo, nystagmus
 Spinothalamic tract, spinal trigeminal nucleus ➝ contralat. Body & ipsilateral face has  pain, To
 Sympathetic tract fibers ➝ ipsilateral Horner Syndrome
 Middle and inferior cerebellar peduncle ➝ ipsilateral dysmetria (past-pointing), ataxia, (Dashing)
o Posterior inferior cerebellar artery (PICA)
 Lateral medulla includes nucleus ambiguous (CN 9, 10, 11) + vestibular nuclei
 Nucleus ambiguous (Lateral medullary (Wallenberg) syndrome)
 Dysphagia,  gag reflex
 Hoarseness, hiccups
 Vestibular nuclei ➝ vomiting, vertigo, nystagmus
 Lateral spinothalamic tract, spinal trigeminal nucleus ➝ contralat. Body & ipsilateral face has  pain, To
 Sympathetic fibers ➝ ipsilateral Horner Syndrome
 Inferior cerebellar peduncle ➝ ipsilateral dysmetria (past-pointing), ataxia, (Dashing)
o Anterior spinal artery
 Lateral corticospinal tract (medial medullary syndrome)
 Caused by infarct of paramedian branches of ASA and/or vertebral A.
 Contralateral paralysis of UL and LL
 Medial lemniscus ➝  contralateral proprioception
 Caudal medulla—hypoglossal nerve ➝ Ipsilateral hypoglossal dysfunction (tongue deviates ipsilaterally).
 Medial
Midbrain CN 3, 4 (CN 1, 2 are outside brainstem)
Pons CN 6 arises from medial pons
Supplied by basilar artery (Locked-In Syndrome)
Medulla CN 12 arises from medial medulla
Supplied by ASA (medial medullary syndrome)
4 Midline Structures:
- Midline motor nuclei: ipsilateral CN deficit
- MLF: Ipsilateral INO
- Motor Tracts: Contralateral weakness
- Medial Lemniscus: Contralateral DCML loss
Lateral
-
CN 5, 7, 8 arises from lateral pons
Supplied by AICA (lateral pontine syndrome)
CN 9, 10, 11
Supplied by PICA (lateral medullary syndrome)
4 Side (Lateral) Structures:
- Sympathetic Tract: Ipsilateral Horner's
- Spinocerebellar Tracts: Ipsilateral ataxia
- Sensory Trigeminal Nucleus: Ipsilateral
facial pain/temperature
- Spinothalamic: Contralat. Pain/To loss

Figure 2: AV malformation

Intracerebral Hemorrhagic Stroke

 Fetal Intraventricular Hemorrhage (Germinal Matrix Hemorrhage)
o Bleed in germinal matrix of ventricles (vascular layer in subventricular zone from which neuron & glial cells
develop)
o  risk in premature & LBW infants due to  glial fiber support & impaired autoregulation of BP.
o Presentation with bulging fontanelle, hypotension, seizures, altered consciousness, coma.
o USG: blood in intraventricular spaces (A)
 Intraparenchymal hemorrhage
o Cause
 HT* (Charcot-Bouchard microaneurysm); bleed in putamen (G) then thalamus, pons, cerebellum (H)
 Amyloid angiopathy (recurrent lobar hemorrhagic stroke in older adults),
 arteriovenous malformations (MC cause of intracranial hemorrhage in children ➝ single lesion)
 vasculitis, neoplasm.
 May be 2o to reperfusion injury in ischemic stroke.
 Epidural Hematoma
o Rupture of middle meningeal artery (branch of maxillary artery),
o often 2° to skull fracture (circle in A) involving pterion (thinnest area of lateral skull).
o Presentation
 transient loss of consciousness, recovery (“lucid interval”), then rapid deterioration d/t hematoma
expansion.
 Scalp hematoma (arrows in A) & rapid intracranial expansion (arrows in B) under systemic arterial
pressure
 Trans-tentorial herniation
 CN III palsy
o CT shows biconvex (lentiform), hyperdense blood collection B not crossing suture lines.
 Subdural hematoma
o Rupture of bridging veins.
o Acute (traumatic, high-energy impact ➝ hyperdense on CT) or chronic (associated with mild trauma, cerebral
atrophy, age, chronic alcohol overuse ➝ hypodense on CT). Also seen in shaken babies.
o 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 hemorrhage
 o Bleeding (E, F) due to trauma, or rupture of an aneurysm (such as a saccular aneurysm) or arteriovenous
malformation.
o Rapid time course.
o Patients complain of “worst headache of my life.” Bloody or yellow (xanthochromic) lumbar puncture.
o Vasospasm can occur due to blood breakdown or rebleed 3–10 days after hemorrhage ➝ ischemic infarct;
nimodipine used to prevent/reduce vasospasm.risk of developing communicating and/or obstructive
hydrocephalus.

 Pain
oCentral Post-stroke pain
 A Neuropathic pain due to thalamic lesions. Initial paresthesias followed in weeks to months by allodynia
(ordinarily painless stimuli cause pain) and dysesthesia (altered sensation) on the contralateral side. Occurs
in 10% of stroke patients.
o Phantom Limb pain
 A Sensation of pain in a limb that is no longer present. Common after amputation. Associated with
reorganization of 1° somatosensory cortex. Characterized by burning, aching, or electric shock– like pain.
 Diffuse Axonal injury
o A Traumatic shearing of white matter tracts during rapid acceleration and/or deceleration of the brain (eg, motor
vehicle accident). Usually results in devastating neurologic injury, often causing coma or persistent vegetative state.

MRI shows multiple lesions (punctate hemorrhages) involving white matter tracts A.
 Aphasia
o A Aphasia—higher-order language deficit (inability to understand/produce/use language appropriately); caused by
pathology in dominant cerebral hemisphere (usually left).
o Dysarthria—motor inability to produce speech (movement deficit).
o Broca (Expressive)
 A Broca area in inferior frontal gyrus of frontal lobe. Associated with defective language production.
Patients appear frustrated, insight intact.
 Broca = broken boca (boca = mouth in Spanish).
o Wernicke (Receptive)
 A Wernicke area in superior temporal gyrus of temporal lobe. Associated with impaired language
comprehension. Patients do not have insight.
 Wernicke is a word salad and makes no sense.
o Conduction ➝ caused by damage to arcuate fasciculus
o Global ➝ Broca and Wernicke areas affected.


 Aneurysms
o Abnormal dilation of an artery due to weakening of vessel wall.
o Saccular aneurysm / Berry aneurysm
  A Also called berry aneurysm A . Occurs at bifurcations in the circle of Willis. Most common site is
junction of ACom and ACA. Associated with ADPKD, Ehlers-Danlos syndrome. Other risk factors:
advanced age, hypertension, tobacco smoking.
 Usually clinically silent until rupture (most common complication)¬ésubarachnoid hemorrhage ("worst
headache of my life" or "thunderclap headache")Žfocal neurologic deficits. Can also cause symptoms via
direct compression of surrounding structures by growing aneurysm.
 ACom-compression ¬é bitemporal hemianopia (compression of optic chiasm); visual acuity
 deficits; rupture¬éischemia in ACA distribution¬écontralateral lower extremity hemiparesis,
 sensory deficits.
 MCA-rupture ¬é ischemia in MCA distribution ¬é contralateral upper extremity and lower
 facial hemiparesis, sensory deficits.
 PCom-compression ¬é ipsilateral CN III palsy ¬é mydriasis ("blown pupil"); may also see
 ptosis, "down and out" eye.


o Charcot-Bouchard microaneurysm
 A Common, associated with chronic hypertension; affects small vessels (eg, lenticulostriate arteries in basal
ganglia, thalamus) and can cause hemorrhagic intraparenchymal strokes. Not visible on angiography.
 Herniation Syndromes
o Cingulate (subfalcine) herniation under falx cerebri ➝ compresses anterior cerebral artery
o Central/downward trans-tentorial herniation
 Caudal displacement of brainstem ➝ rupture of paramedian basilar artery branches ➝ Duret hemorrhages.
 Usually fatal.
o Uncal trans-tentorial herniation
 A Uncus = medial temporal lobe. Early herniation Žipsilateral blown pupil (unilateral CN III
compression), contralateral hemiparesis. Late herniationŽcoma, Kernohan phenomenon (misleading
contralateral blown pupil and ipsilateral hemiparesis due to contralateral compression against Kernohan
notch).
o Cerebellar tonsillar herniation into foramen magnum ➝ Coma and death result when these herniations compress the
brainstem

o
 Idiopathic Intracranial HT / Pseudotumor cerebri
o A  ICP with no obvious findings on imaging.
o Risk factors include female sex, Tetracyclines, Obesity, vitamin A excess, Danazol (female TOAD). Associated
with dural venous sinus stenosis.
o Findings: headache, tinnitus, diplopia (usually from CN VI palsy), no change in mental status. Impaired optic nerve
axoplasmic flowŽpapilledema. Visual field testing shows enlarged blind spot and peripheral constriction. Lumbar
puncture revealsopening pressure and provides temporary headache relief.
o Treatment: weight loss, acetazolamide, invasive procedures for refractory cases (eg, CSF shunt placement, optic
nerve sheath fenestration surgery for visual loss).
 Hydrocephalus
 o  CSF volume ➝ ventricular dilation w/w/o  ICP
o Communicating
 Communicating hydrocephalus
  CSF absorption by arachnoid granulations (eg, arachnoid scarring post-meningitis) ➝  ICP,
 papilledema, herniation.
 Normal pressure hydrocephalus
 Affects older adults; idiopathic; CSF pressure elevated only episodically; does not result in
increased subarachnoid space volume. Expansion of ventricles A distorts the fibers of the corona
radiataŽtriad of urinary incontinence, gait apraxia (magnetic gait), and cognitive dysfunction.
“Wet, wobbly, and wacky.” Symptoms potentially reversible with CSF drainage via lumbar
puncture or shunt placement.
o Non-communicating (Obstructive)
 Caused by structural blockage of CSF circulation within ventricular system (eg, stenosis of aqueduct of
Sylvius, colloid cyst blocking foramen of Monro, tumor B ).
o Hydrocephalus mimics
 Ex vacuo ventriculomegaly
 Appearance of  CSF on imaging C , but is actually due to  brain tissue and neuronal atrophy
(eg, Alzheimer disease, advanced HIV, frontotemporal dementia, Huntington disease). ICP is
normal; NPH triad is not seen.


 Fever vs Heat Stroke

o

 Seizures
 o A
o Etiology:


o Characterized by synchronized, high-frequency neuronal firing.
o Partial (focal) seizures
 Affect single area of the brain. Most commonly originate in medial temporal lobe.
 Types:
 Simple partial (consciousness intact)- motor, sensory, autonomic, psychic
 Complex partial (impaired consciousness, automatisms)
o Generalized seizures (diffuse)
 Absence (petit mal)-3 Hz spike-and-wave discharges, short (usually 10 seconds) and frequent episodes of
blank stare, no postictal confusion. Can be triggered by hyperventilation
 Myoclonic-quick, repetitive jerks; no loss of consciousness
 Tonic-clonic (grand mal)-alternating stiffening and movement, postictal confusion, urinary incontinence,
tongue biting
 Tonic-stiffening
 Atonic-"drop" seizures (falls to floor); commonly mistaken for fainting
o Epilepsy—disorder of recurrent, unprovoked seizures (febrile seizures are not epilepsy).
o Status epilepticus
 continuous (≥ 5 min) or recurring seizures without interictal return to baseline consciousness that may
result in brain injury.
 Headaches
o Pain due to irritation of intra- or extracranial structures (eg, meninges, blood vessels). Primary headaches include
cluster, migraine, and tension; migraine and tension headaches are more common in females. Secondary headaches
include subarachnoid hemorrhage, meningitis, hydrocephalus, neoplasia, giant cell (temporal) arteritis.
o Cluster Headache
 Unilateral headache lasting for 15 – 3 hr; repetitive (MC in males)
 CF
 Excruciating periorbital pain (“suicide headache”) with autonomic symptoms (eg, lacrimation,
rhinorrhea, conjunctival injection).
 May present with Horner syndrome.
 Treatment
 acute: sumatriptan, 100% O2
 Prophylaxis: verapamil
o Migraine (POUND – Pulsatile, One-day duration, Unilateral, Nausea, Disabling)
  Unilateral headache lasting for 4 – 72 hr
 CF
 Pulsating pain with nausea, photophobia, and/or phonophobia. May have “aura.” Due to irritation
of CN V, meninges, or blood vessels (release of vasoactive neuropeptides [eg, substance P,
calcitonin gene-related peptide]).
 Treatment
 Acute: NSAIDs, triptans, dihydroergotamine, antiemetics (eg, prochlorperazine, metoclopramide).
 Prophylaxis: lifestyle changes (eg, sleep, exercise, diet), β-blockers, amitriptyline, topiramate,
valproate, botulinum toxin, anti-CGRP monoclonal antibodies.
o Tension Headache
 Bilateral headache lasting >30 min (typically 4 – 6hr); constant
 CF ➝ Steady, “band-like” pain (NO photophobia or phonophobia or aura)
 Treatment
 Acute: analgesics, NSAIDs, acetaminophen.
 Prophylaxis: TCAs (eg, amitriptyline), behavioral therapy.
o Trigeminal neuralgia
 produces repetitive, unilateral, shooting/shocklike pain in the distribution of CN V.
 Triggered by chewing, talking, touching certain parts of the face.
 Lasts (typically) for seconds to minutes, but episodes often increase in intensity and frequency over time.
 First-line therapy: carbamazepine.
 Movement Disorders
o
Neurodegenerative Disorders
  in cognitive ability, memory, or function with intact consciousness.
 Must rule out depression as cause of dementia (called pseudodementia). Other reversible causes of dementia:
hypothyroidism, vitamin B12 deficiency, neurosyphilis, normal pressure hydrocephalus.
 Parkinson Disease
o TRAPS
 Tremors (pill-rolling tremors at rest)
 Rigidity (cogwheel)
 Akinesia (or bradykinesia) Postural instability
 Shuffling gait
 Small handwriting (micrographia)
 Dementia is usually a late finding. MPTP, a contaminant in illegal drugs, is metabolized to MPP+, which is
toxic to substantia nigra.
o Histologic / Gross findings
 A Loss of dopaminergic neurons (ie, depigmentation) of substantia nigra pars compacta.
 Lewy bodies: composed of α-synuclein (intracellular eosinophilic inclusions A ).


 Huntington Disease
o A Autosomal dominant trinucleotide (CAG)n repeat expansion in the huntingtin (HTT) gene on chromosome 4 (4
letters) ➝ toxic gain of function.
o CF (20 – 50 year-old) ➝ chorea, athetosis, aggression, depression, dementia (initially mistaken for substance use)
o Anticipation results from expansion of CAG repeats. Caudate loses ACh and GABA.
o Histologic / Gross findings
 Atrophy of caudate and putamen with ex vacuo ventriculomegaly.
  dopamine,  GABA,  ACh in brain.
 Neuronal death via NMDA-R binding and glutamate excitotoxicity.
 Alzheimer Disease
o MC cause of dementia in older adults
o A Advanced age is the strongest risk factor. Down syndrome patients haverisk of developing early-onset
Alzheimer disease, as APP is located on chromosome 21.
o ACh.
o Associated with the following altered proteins:
 ApoE-2:  risk of sporadic form
 ApoE-4:  risk of sporadic form
 APP, presenilin-1, presenilin-2: familial forms (10%) with earlier onset ApoE-2 is “protwoctive”, apoE-4 is
“four” Alzheimer disease.
o Histologic / Gross findings
 Widespread cortical atrophy (normal cortex B ; cortex in Alzheimer disease C ), especially hippocampus
(arrows in B and C ). Narrowing of gyri and widening of sulci.
 Senile plaques D in gray matter: extracellular β-amyloid core; may cause amyloid angiopathy Žintracranial
hemorrhage; Aβ (amyloid-β) synthesized by cleaving amyloid precursor protein (APP).
 Neurofibrillary tangles E : intracellular, hyperphosphorylated tau protein = insoluble cytoskeletal elements;
number of tangles correlates with degree of dementia.
 Hirano bodies—intracellular eosinophilic proteinaceous rods in hippocampus.
 Frontotemporal Dementia (Pick Disease)
o A Early changes in personality and behavior (behavioral variant), or aphasia (primary progressive aphasia).
o May have associated movement disorders.
o Histologic / Gross findings
 Frontotemporal lobe degeneration F . Inclusions of hyperphosphorylated tau (round
 Pick bodies G ) or ubiquitinated TDP-43.
 Lewy Body Dementia
 o Visual hallucinations (“haLewycinations”), dementia with fluctuating cognition/ alertness, REM sleep behavior
disorder, and parkinsonism. Called Lewy body dementia if cognitive and motor symptom onset < 1 year apart,
otherwise considered dementia 2° to Parkinson disease.
o Histologic / Gross findings ➝ intracellular Lewy bodies primarily in cortex (A)
 Vascular Dementia
o A Result of multiple arterial infarcts and/or chronic ischemia.
o Step-wise decline in cognitive ability with late- onset memory impairment. 2nd most common cause of dementia in
older adults.
o MRI or CT shows multiple cortical and/or subcortical infarcts
 Creutzfeldt-Jakob Disease
o A Rapidly progressive (weeks to months) dementia with myoclonus (“startle myoclonus”) and ataxia. Associated
with periodic sharp waves on EEG and  14-3-3 protein in CSF. May be transmitted by contaminated materials (eg,
corneal transplant, neurosurgical equipment). Fatal.
o Histologic / Gross findings
 A Spongiform cortex (vacuolation without inflammation).
 Prions (PrPc ➝ PrPsc sheet [β-pleated sheet resistant to proteases]) H .
 HIV-associated Dementia
o A Subcortical dysfunction associated with advanced HIV infection. Characterized by cognitive deficits, gait
disturbance, irritability, depressed mood.
o Histologic / Gross findings
 Diffuse gray matter and subcortical atrophy.
 Microglial nodules with multinucleated giant cells.


Demyelinating and Demyelinating Disorders
 Multiple Sclerosis
o Autoimmune inflammation and demyelination of CNS (brain and spinal cord) with subsequent axonal damage.
o Presentation
 Optic neuritis (acute painful monocular visual loss, associated with relative afferent pupillary defect)
 Brainstem/cerebellar syndromes (e.g., diplopia, ataxia, scanning speech, intention tremor, nystagmus/INO
[bilateral > unilateral])
 Pyramidal tract demyelination (eg, weakness, spasticity)
 Spinal cord syndromes (eg, electric shock-like sensation along cervical spine on neck flexion, neurogenic
bladder, paraparesis, sensory manifestations affecting the trunk or one or more extremity)
 Symptoms may exacerbate with increased body temperature (eg, hot bath, exercise).
 Relapsing and remitting is most common clinical course.
 Most often affects females in their 20s and 30s; more common in individuals who grew up farther from
equator and with low serum vitamin D levels.
o Investigations
  IgG level and myelin basic protein in CSF. Oligoclonal bands aid in diagnosis. MRI is gold standard.
Periventricular plaques A (areas of oligodendrocyte loss and reactive gliosis). Multiple white matter lesions
disseminated in space and time.
o Treatment
 Stop relapses and halt/slow progression with disease-modifying therapies (eg, B-interferon, glatiramer,
natalizumab).
 Treat acute flares with IV steroids.
 Symptomatic treatment for
 neurogenic bladder (catheterization, muscarinic antagonists, botulinum toxin injection),
 spasticity (baclofen, GABAB receptor agonists),
 pain (TCAs, anticonvulsants).

o
 Acute Inflammatory Demyelinating Polyneuropathy (MC subtype of Guillain-Barre Syndrome)
o A Autoimmune condition that destroys Schwann cells via inflammation and demyelination of motor
o fibers, sensory fibers, peripheral nerves (including CN III-XII). Likely facilitated by molecular mimicry and
triggered by inoculations or stress. Despite association with infections (eg, Campylobacter jejuni, viruses [eg, Zika]),
no definitive causal link to any pathogen.
o Results in symmetric ascending muscle weakness/paralysis and depressed/absent DTRs beginning in lower
extremities. Facial paralysis (usually bilateral) and respiratory failure are common. May see autonomic
dysregulation (eg, cardiac irregularities, hypertension, hypotension) or sensory abnormalities. Most patients survive
with good functional recovery.
o CSF protein with normal cell count (albuminocytologic dissociation).
o Respiratory support is critical until recovery. Disease-modifying treatment: plasma exchange or
 o IV immunoglobulins. No role for steroids.
 Osmotic Demyelination Syndrome (Central Pontine Myelinolysis)
o Massive axonal demyelination in pontine white matter A 2° to rapid osmotic changes, most commonly iatrogenic
correction of hyponatremia but also rapid shifts of other osmolytes (eg, glucose).
o Acute paralysis, dysarthria, dysphagia, diplopia, loss of consciousness.
o Can cause “locked-in syndrome.”
o Correcting serum Na+ too fast:
 “From low to high, your pons will die” (osmotic demyelination syndrome)
 “From high to low, your brains will blow” (cerebral edema/herniation)


 Charcot-Marie-Tooth Disease (Hereditary Motor and Sensory Neuropathy)
o Group of progressive hereditary nerve disorders related to the defective production of proteins involved in the
structure and function of peripheral nerves or the myelin sheath.
o Typically, autosomal dominant and associated with foot deformities (eg, pes cavus, hammer toe), lower extremity
weakness (eg, foot drop), and sensory deficits (Can’t Move Toes).
o Most common type, CMT1A, is caused by PMP22 gene duplication.
 Progressive multifocal Leukoencephalopathy
o A Demyelination of CNS B due to destruction of oligodendrocytes (2° to reactivation of latent JC virus infection).
Associated with severe immunosuppression (eg, lymphomas and leukemias, AIDS, organ transplantation).
o Rapidly progressive, usually fatal. Predominantly involves parietal and occipital areas; visual symptoms are
common.
o  risk associated with natalizumab.

o
 Acute Disseminated (post-infectious) Encephalomyelitis
o Multifocal inflammation and demyelination after infection or vaccination.
o Presents with rapidly progressive multifocal neurologic symptoms, altered mental status.
 Other Disorders
o Krabbe Disease
o Metachromatic leukodystrophy
o Adrenoleukodystrophy
Neurocutaneous Disorders
 Sturge-Weber Syndrome (Encephalotrigeminal Angiomatosis)
o Genetics
 Congenital nonhereditary anomaly of neural crest derivatives. Somatic mosaicism of an activating mutation
in one copy of the GNAQ gene.
o Presentations
 Capillary vascular malformation➝ port-wine stain A (nevus flammeus or non- neoplastic birthmark) in CN
V1/V2 distribution;
 ipsilateral leptomeningeal angioma with calcifications B ➝ seizures/ epilepsy;
 intellectual disability;
 episcleral hemangioma ➝  IOP ➝ early-onset glaucoma.
 Tuberous Sclerosis
o Genetics
o Presentations
  incidence of subependymal giant cell astrocytoma and ungual fibromas
 A Hamartomas in CNS and skin, angiofibromas
 C , mitral regurgitation, ash-leaf spots D ,
 cardiac rhabdomyoma, intellectual disability, renal angiomyolipoma E ,
 seizures, shagreen patches.
 Neurofibromatosis Type I (Von Recklinghausen disease)
o Genetics
 AD, 100% penetrance.
 Mutation in NF1 tumor suppressor gene on chromosome 17 (encodes neurofibromin, a negative RAS
regulator).
o Presentations (CICLOPS)
 Café-au-lait spots F ,
 Intellectual disability,
 Cutaneous neurofibromas G ,
 Lisch nodules (pigmented iris hamartomas H ),
 Optic gliomas,
 Pheochromocytomas,
 Seizures/focal neurologic Signs (often from meningioma),
 bone lesions (eg, sphenoid dysplasia).
 Neurofibromatosis Type II
o Genetics ➝ AD. Mutation in NF2 tumor suppressor gene (merlin) on chromosome 22.
o Presentations
 NF2 affects 2 ears, 2 eyes
 Bilateral vestibular schwannomas, juvenile cataracts, meningiomas, ependymomas.
 Von Hippel-Lindau Disease
o Genetics
 VHL (3 letters) ➝ chromosome 3; associated with RCC (also 3 letters)
 AD. Deletion of VHL gene on chromosome 3p. pVHL ubiquitinates hypoxia- inducible factor 1a.
o Presentations (HARP)
 Hemangioblastoma (high vascularity with hyperchromatic nuclei I) in retina, brainstem, cerebellum, spine J
 Angiomatosis;
 bilateral Renal cell carcinomas;
 Pheochromocytomas.
Spinal Lesions
 Motor Neuron Signs


 Spinal Muscular Atrophy
o SMA type I is called Werdnig-Hoffmann Disease
o Congenital degeneration of anterior horns.
o LMN symptoms only, symmetric weakness.
o “Floppy baby” with marked hypotonia (flaccid paralysis) and tongue fasciculations.
o Autosomal recessive SMN1 mutation ➝ defective snRNP assembly.
 Amyotrophic Lateral Sclerosis (ALA aka Lou Gehrig Disease)
o Combined UMN (corticobulbar/corticospinal) and LMN (medullary and spinal cord) degeneration. No sensory or
bowel/bladder deficits.
o Can be caused by defect in superoxide dismutase 1.
o LMN deficits: flaccid limb weakness, fasciculations,
o atrophy, bulbar palsy (dysarthria, dysphagia, tongue atrophy).
o UMN deficits: spastic limb weakness, hyperreflexia, clonus, pseudobulbar palsy (dysarthria, dysphagia, emotional
lability). Fatal (most often from respiratory failure).
o Treatment: “riLouzole”.
 Poliomyelitis
o Caused by poliovirus (fecal-oral transmission).
o Replicates in lymphoid tissue of oropharynx and small intestine before spreading via bloodstream to CNS.
o Infection causes destruction of cells in anterior horn of spinal cord (LMN death).
o Signs of LMN lesion: asymmetric weakness (vs symmetric weakness in spinal muscular atrophy), hypotonia, flaccid
paralysis, fasciculations, hyporeflexia, muscle atrophy.
o Respiratory muscle involvement leads to respiratory failure.
o Signs of infection: malaise, headache, fever, nausea, etc.
o CSF shows  WBCs (lymphocytic pleocytosis) and slight  of protein (with no change in CSF glucose). Virus
recovered from stool or throat.
 Syringomyelia
o Syrinx expands and damages anterior white commissure of spinothalamic tract (2nd-order neurons) ➝ bilateral
symmetric loss of pain and temperature sensation in cape-like distribution.
o Seen with Chiari I malformation. Can affect other tracts.
 Subacute Combined Degeneration
o SCD is due to vitamin B12 deficiency
o demyelination of Spinocerebellar tracts, lateral Corticospinal tracts, and Dorsal columns.
o Ataxic gait, paresthesia, impaired position/vibration sense (⊕ Romberg sign), UMN symptoms.
 Tabes Dorsalis
o Caused by 3° syphilis. Results from degeneration/ demyelination of dorsal columns and roots ➝ progressive sensory
ataxia (impaired proprioception ➝ poor coordination). ⊕ Romberg sign and absent DTRs. Associated with Charcot
joints, shooting pain, Argyll Robertson pupils.
 Complete Occlusion of Anterior Spinal Artery
 o Spares dorsal columns and Lissauer tract; mid-thoracic ASA territory is watershed area, as artery of Adamkiewicz
supplies ASA below T8.
o Can be caused by aortic aneurysm repair.
o 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 below the lesion (spinothalamic tract).
 Cauda equina Syndrome
o Compression of spinal roots L2 and below, often due to intervertebral disc herniation or tumor.
o Radicular pain, absent knee and ankle reflexes, loss of bladder and anal sphincter control, saddle anesthesia.
 Friedreich Ataxia
o Autosomal recessive trinucleotide repeat disorder (GAA) n on chromosome 9 in gene that encodes frataxin (iron-
binding protein).
o Leads to impairment in mitochondrial functioning.
o Degeneration of lateral corticospinal tract (spastic paralysis), spinocerebellar tract (ataxia), dorsal columns ( 
vibratory sense, proprioception), and dorsal root ganglia (loss of DTRs).
o Staggering gait, frequent falling, nystagmus, dysarthria, pes cavus, hammer toes, diabetes mellitus, hypertrophic
cardiomyopathy (cause of death). Presents in childhood with kyphoscoliosis A .
o Friedreich is fratastic (frataxin): he’s your favorite frat brother, always staggering and falling but has a sweet, big
heart. Ataxic GAAit.
 Brown-Sequard Syndrome
o Hemi-section of spinal cord.
o Findings:
 Ipsilateral loss of all sensation at level of lesion
 Ipsilateral LMN signs (eg, flaccid paralysis) at level of lesion
 Ipsilateral UMN signs below level of lesion (due to corticospinal tract damage) Ipsilateral loss of
proprioception, vibration, and light (2-point discrimination) touch below level of lesion (due to dorsal
column damage)
 Contralateral loss of pain, temperature, and crude (non-discriminative) touch below level of lesion (due to
spinothalamic tract damage)
o If lesion occurs above T1, patient may present with ipsilateral Horner syndrome due to damage of oculosympathetic
pathway.

Cranial Nerve Lesions

 CN V motor lesion ➝ Jaw deviates toward side of lesion due to unopposed force from 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).
 CN XII (LMN) lesion ➝ tongue deviates toward side of lesion (“lick your wounds”) d/t weak tongue muscles on affected
side
 CN VII lesion (facial nerve lesion)
o Causes of peripheral facial palsy
 Bell’s Palsy* (MC)
 herpes zoster (Ramsay Hunt syndrome),
 Lyme disease,
 sarcoidosis,
 tumors (eg, parotid gland),
 diabetes mellitus.
o Usually develops after HSV reactivation.
o UMN lesions are contralateral
 Location is motor cortex ➝ connection from motor cortex to facial nucleus in pons is cut
 Muscles ➝ lower muscles of facial expression BUT forehead is spared due to bilateral UMN innervation
o LMN lesions are ipsilateral
 Location is facial nucleus, anywhere along CN VII
 Muscles ➝ upper and lower muscles of facial expression (forehead is affected)
 Other symptoms
 Incomplete eye closure (dry eyes, corneal ulceration)
 Hyperacusis
 Loss of taste sensation to anterior tongue
o Treatment: glucocorticoids +/– acyclovir ➝ Most gradually recover function, but aberrant regeneration can occur.


 

Adults 1o Brain Tumors

 Glioblastoma
o Grade IV astrocytoma. Common, highly malignant 1° brain tumor with ~ 1-year median survival. Found in cerebral
hemispheres. Can cross corpus callosum (“butterfly glioma” A ). Associated with EGFR amplification.
o Histology
 Astrocyte origin, GFAP ⊕.
 “Pseudopalisading” pleomorphic tumor cells B border central areas of necrosis, hemorrhage, and/or
microvascular proliferation.
 Oligodendroglioma
o Rare, slow growing tumor in frontal lobes (often calcified) C.
o Histology
 Oligodendrocyte origin. “Fried egg” cells—round nuclei with clear cytoplasm D .
 “Chicken-wire” capillary pattern.
 Meningioma
o Common, benign. Females > males. Occurs along surface of brain or spinal cord.
o Extra-axial (external to brain parenchyma) and may have a dural attachment (“tail” E ). Often asymptomatic; may
present with seizures or focal neurologic signs. Resection and/or radiosurgery.
o Histology
 Arachnoid cell origin.
 Spindle cells concentrically arranged in a whorled pattern F ;
 psammoma bodies (laminated calcifications).
 Hemangioblastoma
o Most often cerebellar G .
o Associated with von Hippel-Lindau syndrome when found with retinal angiomas.
o Can produce erythropoietin ➝ 2° polycythemia.
o Histology ➝ Blood vessel origin. Closely arranged, thin- walled capillaries with minimal intervening parenchyma H
 Pituitary Adenoma
o May be non-functioning (silent) or hyperfunctioning (hormone-producing).
o Non-functional tumors present with mass effect (eg, bitemporal hemianopia [due to pressure on optic chiasm I ]).
Pituitary apoplexy ➝ hypopituitarism.
o Prolactinoma classically presents as galactorrhea, amenorrhea, bone density due to suppression of estrogen in
females and as  libido, infertility in males.
o Histology
 Hyperplasia of only one type of endocrine cells found in pituitary.
 Most commonly from lactotrophs (prolactin) J ➝ hyperprolactinemia.
 Less commonly, from somatotrophs (GH) ➝ acromegaly, gigantism;
 corticotrophs (ACTH) ➝ Cushing disease.
 Rarely, from thyrotrophs (TSH), gonadotrophs (FSH, LH).
o Treatment: dopamine agonists (eg, bromocriptine, cabergoline), transsphenoidal resection.
 Schwannoma
o Benign tumor at cerebellopontine angle K, involving CNs V, VII, and VIII, but can be along any peripheral nerve.
o Often localized to CN VIII in internal acoustic meatus ➝ vestibular schwannoma (can present as hearing loss and
tinnitus).
o Bilateral vestibular schwannomas found in NF-2.
o Histology
 Schwann cell origin, S-100 ⊕.
 Biphasic, dense, hypercellular areas containing spindle cells alternating with hypocellular, myxoid areas L
o Treatment: Resection or stereotactic radiosurgery.
Childhood 1o Brain Tumors
 Pilocytic Astrocytoma
o Low-grade astrocytoma. Most common 1° brain tumor in childhood. Usually well circumscribed. In children, most
often found in posterior fossa A (eg, cerebellum). May be supratentorial. Benign; good prognosis.
o Histology
 Astrocyte origin, GFAP ⊕. Bipolar neoplastic cells with hairlike projections. Associated with microcysts
and Rosenthal fibers (eosinophilic, corkscrew fibers B ). Cystic + solid (gross).
 Medulloblastoma
o Most common malignant brain tumor in childhood. Commonly involves cerebellum
o C . Can compress 4th ventricle, causing noncommunicating hydrocephalus ➝ headaches, papilledema.
o Can involve the cerebellar vermis ➝ truncal ataxia. Can send “drop metastases” to spinal cord.
o Histology
 A Form of primitive neuroectodermal tumor (PNET). Homer-Wright rosettes (small blue cells surrounding
central area of neuropil D ).
 Synaptophysin ⊕.
 Ependymoma (poor prognosis)
o MC found in 4th ventricle E ➝ Can cause hydrocephalus
o Histology
 Ependymal cell origin.
 Characteristic perivascular pseudorosettes F .
 Rod-shaped blepharoplasts (basal ciliary bodies) found near the nucleus.
 Craniopharyngioma
o MC childhood supra-tentorial tumor
o May be confused with pituitary adenoma (both cause bitemporal hemianopia). Associated with a high recurrence
rate.
o Histology
 Derived from remnants of Rathke pouch (ectoderm).
 Calcification is common G H .
 Cholesterol crystals found in “motor oil”-like fluid within tumor.
 Pineal Gland Tumors
o MC extragonadal germ cell tumors
o  incidence in males
o Present with obstructive hydrocephalus (compression of cerebral aqueduct), Parinaud syndrome (compression of
dorsal midbrain)—triad of upward gaze palsy, convergence-retraction nystagmus, and light-near dissociation.
o Histology ➝ Similar to testicular seminomas
Auditory (Otology)
 Outer Ear
o Visible portion of ear (pinna) includes auditory canal and tympanic membrane.
o Transfers sound waves via vibration of tympanic membrane.
 Middle Ear
o Air-filled space with three bones called the ossicles (malleus, incus, stapes).
o Ossicles conduct and amplify sound from tympanic membrane to inner ear.
 Inner Ear
o Snail-shaped, fluid-filled cochlea contains basilar membrane that vibrates 2° to sound waves.
o Vibration transduced via specialized hair cells ➝ auditory nerve signaling ➝ brainstem.
o 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).
 Otitis externa (external auditory canal)
o Inflammation of external auditory canal.
o Cause ➝ pseudomonas (MC) associated w H2O exposure (swimmer’s ear), ear canal trauma/occlusion (hearing aid)
o Presents with otalgia that worsens with ear manipulation, pruritus, hearing loss, discharge. Malignant (necrotizing)
otitis externa—invasive infection causing osteomyelitis.
o Complication seen in older patients with diabetes.
o Presents with severe otalgia and otorrhea.
o Physical exam shows granulation tissue in ear canal.
 Otitis media (middle ear)
o Inflammation of middle ear.
o Most commonly due to non-typeable Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis.
o Associated with eustachian tube dysfunction, which promotes overgrowth of bacterial colonizers of upper
respiratory tract.
o Usually seen in children < 2 years old. Presents with fever, otalgia, hearing loss. Physical exam shows bulging,
erythematous tympanic membrane that may rupture.
o Mastoiditis
 infection of mastoid process of temporal bone.
 Complication of acute otitis media due to continuity of middle ear cavity with mastoid air cells.
 Presents with postauricular pain, erythema, swelling. May lead to brain abscess.
 Cholesteatoma (middle ear)
o Abnormal growth of keratinized squamous epithelium in middle ear A (“skin in wrong place”).
o Usually acquired, but can be congenital.
o 1° acquired results from tympanic membrane retraction pockets that form due to eustachian tube dysfunction.
o 2° acquired results from tympanic membrane perforation (eg, d/t otitis media) that permits migration of squamous
epithelium to middle ear.
o Classically presents with painless otorrhea.
o May erode ossicles ➝ conductive hearing loss.
 Hearing Loss
o Noise-induced hearing loss
 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.
o Presbycusis
 Aging-related progressive bilateral/symmetric sensorineural hearing loss (often of higher frequencies) due
to destruction of hair cells at the cochlear base (preserved low-frequency hearing at apex).
 o Diagnosing hearing loss

 Vertigo
o Sensation of spinning while actually stationary
o Subtype of “dizziness”, but distinct from “lightheadedness.” Peripheral vertigo is more common than central vertigo.
 Peripheral vertigo is due to inner ear pathologies such as
 semicircular canal debris (benign paroxysmal positional vertigo),
 vestibular neuritis,
 Ménière disease—endolymphatic hydrops ( endolymph in inner ear) ➝ triad of vertigo, sensorineural
hearing loss, tinnitus (“men wear vests”).
 Findings: mixed horizontal-torsional nystagmus (never purely torsional or vertical) that does not change
direction and is suppressible with visual fixation.
 Central vertigo
o Brain stem or cerebellar lesion (eg, stroke affecting vestibular nuclei, demyelinating disease, or posterior fossa
tumor).
o Findings:
 nystagmus of any direction that is not suppressible with visual fixation,
 neurologic findings (eg, diplopia, ataxia, dysmetria).


Ophthalmology
 Normal Eye Anatomy

o
 Conjunctivitis
o Inflammation of the conjunctiva ➝ red eye
o Allergic—bilateral itchy eyes
o Bacterial—pus, treat with antibiotics
o Viral—MC, often adenovirus; sparse mucous discharge, swollen preauricular node,  lacrimation; self-resolving
 Refractive Errors
o Common cause of impaired vision, correctable with glasses.
o Hyperopia (far-sightedness)
 Eye too short for refractive power of cornea and lens ➝ light focused behind retina.
 Correct with convex (converging) lenses.
o Myopia (near-sightedness)
 Eye too long for refractive power of cornea and lens ➝ light focused in front of retina.
 Correct with concave (diverging) lens.
o Astigmatism
 Abnormal curvature of cornea ➝ different refractive power at different axes.
 Correct with cylindrical lens.
 Leukocoria ➝ Loss (whitening) of red reflex. Important causes in children include retinoblastoma (A), congenital cataract.
 Lens Disorders
o Presbyopia
 Aging-related impaired accommodation (focusing on near objects), primarily due to  lens elasticity.
 Patients often need reading glasses or magnifiers
o Cataract
 Bilateral painless opacification of lens A resulting in glare and  vision, esp. at night, and loss of red reflex.
  Acquired risk factors:
  age, diabetes mellitus, trauma, infection.
 tobacco smoking, alcohol overuse, excessive sunlight, prolonged glucocorticoid use,
 Congenital risk factors:
 classic galactosemia,
 galactokinase deficiency,
 trisomies (13, 18, 21),
 TORCH infections (e.g., rubella),
 Marfan syndrome,
 Alport syndrome,
 myotonic dystrophy,
 NF-2.
 Treatment: surgical removal of lens and replacement with an artificial lens.
o Lens dislocation (ectopia lentis)
 Displacement or malposition of lens due to trauma,
 May also occur in association with systemic diseases (eg, Marfan syndrome, homocystinuria).

 Aqueous Humor Pathway

o
 Glaucoma
o Optic neuropathy causing progressive vision loss (peripheral ➝ central).
o Usually, but not always, accompanied by  IOP.
o Etiology is most often 1°, but can be 2° to an identifiable cause (e.g., uveitis, glucocorticoids).
o Fundoscopy: optic disc cupping (normal A vs thinning of outer rim of optic disc B).
o Treatment: pharmacologic or surgical lowering of IOP.
o Open Angle Glaucoma (MC type in US)
 Anterior chamber angle is open (normal).
 Associated with  resistance to aqueous humor drainage through trabecular meshwork.
 Risk factors ➝  age, race (in Blacks), family history, diabetes mellitus.
 Typically, asymptomatic and discovered incidentally.
o Angle Closure Glaucoma
 Anterior chamber angle is narrowed or closed C .
 Associated with anatomic abnormalities (e.g., anteriorly displaced lens resting against central iris) ➝ 
aqueous flow through pupil (pupillary block) ➝ pressure buildup in posterior chamber ➝ peripheral iris
pushed against cornea ➝ obstruction of drainage pathways by the iris.
 Usually chronic and asymptomatic, but may develop acutely.
 Acute angle-closure glaucoma
 complete pupillary block causing abrupt angle closure and rapid  IOP.
 Presentation (Hurts in a hurry with halos, a headache, and a “half-dilated” pupil)
a. severe eye pain, sudden vision loss,
b. conjunctival erythema D, fixed and mid-dilated pupil.
c. halos around lights, headache, nausea and vomiting,
 Rx ➝ true ophthalmic emergency requires Rx to prevent blindness (Mydriatic are contraindicated)
 

 Retinal Disorders

o Age-related macular degeneration

 Degeneration of macula (central area of retina)¬éloss of central vision (scotomas). Two types:
 Dry (most common)-gradual ¬ê in vision with subretinal deposits (drusen, arrow in A ).
 Wet-rapid ¬ê in vision due to bleeding 2¬∞ to choroidal neovascularization. Distortion of straight
 lines (metamorphopsia) is an early symptom.
o Diabetic retinopathy
 Chronic hyperglycemia ➝ permeability and occlusion of retinal vessels. Two types:
 Nonproliferative (MC)
 microaneurysms, hemorrhages (arrows in B ),
 cotton-wool spots, hard exudates.
 Vision loss mainly due to macular edema.
 Proliferative-
 retinal neovascularization due to chronic hypoxia.
 Abnormal new vessels may cause vitreous hemorrhage and tractional retinal detachment.
o Hypertensive Retinopathy
 Chronic hypertension causes spasm, sclerosis, and fibrinoid necrosis of retinal vessels.
 Fundoscopy:
 arteriovenous nicking,
 microaneurysms, hemorrhages,
 cotton-wool spots (blue arrow in C ), hard exudates (may form macular "star," red arrow in C ).
 Papilledema indicatives hypertensive emergency & warrants immediate lowering of BP.
 o Retinal Artery Occlusion
 Blockage of central/branch retinal artery due to embolism (carotid artery atherosclerosis > cardiogenic);
 less commonly due to giant cell arteritis.
 Presents with acute, painless monocular vision loss.
 Fundoscopy:
 cloudy retina with "cherry-red" spot at fovea D ,
 retinal emboli (cholesterol crystals appear as small, yellow, refractile deposits in arterioles)
o Retinal Vein Occlusion
 Central retinal vein occlusion is due to 1o thrombosis;
 branch retinal vein occlusion is due to 2 o thrombosis at arteriovenous crossings (sclerotic arteriole
compresses adjacent venule causing turbulent blood flow).
 Fundoscopy:
 retinal hemorrhage
 venous engorgement ("blood and thunder" appearance; arrows in E ),
 retinal edema in affected areas.
o Retinal Detachment (surgical emergency)
 Separation of neurosensory retina from underlying retinal pigment epithelium ➝ loss of choroidal blood
supply ➝ hypoxia and degeneration of photoreceptors.
 Rhegmatogenous (MC) d/t retinal tear ➝ asso. w PVD ( risk with advanced age, high myopia) or trauma
 Non-rhegmatogenous ➝ tractional or exudative (fluid accumulation).
 Presentation
 symptoms of posterior vitreous detachment (eg, floaters, light flashes) followed by
 painless monocular vision loss ("dark curtain").
 Fundoscopy:
 opacification and wrinkling of detached retina F ,
 change in vessel direction.
o Retinitis Pigmentosa
 Group of inherited dystrophies causing progressive degeneration of photoR’ & retinal pigment epithelium.
 May be associated with abetalipoproteinemia.
 Early symptoms: night blindness (nyctalopia) and peripheral vision loss.
 Fundoscopy:
 triad of optic disc pallor, retinal vessel attenuation, retinal pigmentation with
 bone spicule-shaped deposits G .
o Papilledema
 Bilateral optic disc swelling due to  ICP (2o to mass effect)
 Results from impaired axoplasmic flow in optic nerve.
 Fundoscopy: elevated optic disc with blurred margins H .
 Uveitis (inflammation of uvea)
o Anterior uveitis is iritis;
o posterior uveitis is choroiditis and/or retinitis.
o Presentation ➝ hypopyon (accumulation of pus in anterior chamber A ) or conjunctival redness.
o Associated with systemic inflammatory disorders like
 sarcoidosis,
 Behçet syndrome,
 juvenile idiopathic arthritis,
 HLA-B27–associated conditions
 Pupillary Control
o Mydriasis (dilation ➝ long ciliary nerves make the pupil diameter longer)
 Sympathetic:
 1st neuron: hypothalamus to ciliospinal center of Budge (C8-T2)
 2nd neuron:
a. exit at T1 to superior cervical ganglion
b. travels along cervical sympathetic chain near lung apex, subclavian vessels
 3rd neuron:
a. plexus along internal carotid, through cavernous sinus;
b. enters orbit as long ciliary nerve to pupillary dilator muscles.
c. Sympathetic fibers also innervate smooth muscle of eyelids (minor retractors) & sweat
glands of forehead and face.
o Miosis (constriction ➝ short ciliary nerves shorten the pupil diameter)
 Parasympathetic:
  1st neuron: Edinger-Westphal nucleus to ciliary ganglion via CN III
 2nd neuron: short ciliary nerves to sphincter pupillae muscles
o Pupillary light reflex
 Light in either retina sends a signal via CN II to pretectal nuclei (dashed lines in image) in midbrain that
activates bilateral Edinger-Westphal nuclei; pupils constrict bilaterally (direct and consensual reflex).
 Result: illumination of 1 eye results in bilateral pupillary constriction.

 Relative Afferent Pupillary Defect (Marcus Gunn pupil)

o Extent of pupillary constriction differs when light is shone in one eye at a time due to unilateral or asymmetric
lesions of afferent limb of pupillary reflex (eg, retina, optic nerve).
o light shined into normal eye ➝ constriction of ipsilateral (direct reflex) & contralateral eye (consensual reflex)
o light swung from normal eye to affected eye ➝ both pupils dilate instead of constricting.
 Horner Syndrome (maple)
o Sympathetic denervation of face:
 Miosis (pupil constriction)
 Anhidrosis (absence of sweating)
 Ptosis (slight drooping of eyelid: superior tarsal muscle) & flushing of affected side of face
o Associated with lesions along the sympathetic chain:
 1st neuron:
 pontine hemorrhage,
 lateral medullary syndrome,
 spinal cord lesion above T1 (e.g., Brown-Sequard syndrome, late-stage syringomyelia)
o 2nd neuron: stellate ganglion compression by Pancoast tumor
o 3rd neuron: carotid dissection (painful); anhidrosis is usually absent

o
 Ocular Motility (SO4, LR6)
o CN VI innervates the Lateral Rectus. CN IV innervates the Superior Oblique. CN III innervates the Rest.
o Obliques go opposite ➝ left SO and IO tested with patient looking right (IOU: IO tested looking UP)
o Blowout Fracture (orbital floor fracture)
  Caused by direct trauma to eyeball or intra-orbital rim.
  risk of IR muscle A and/or orbital fat entrapment
 May lead to infraorbital nerve injury
 Cranial Nerve III palsy/damage
o CN III has both motor (central) and parasympathetic (peripheral) components.
o Common causes include:
 Ischemia ➝ pupil sparing (motor fibers affected more than parasympathetic fibers)
 Uncal herniation ➝ coma
 PCom aneurysm ➝ sudden-onset headache
 Cavernous sinus thrombosis ➝ proptosis, involvement of CNs IV, V1/V2, VI
 Midbrain stroke ➝ contralateral hemiplegia
o Motor output to extraocular muscles (motor is middle while parasympathetic is peripheral)
 affected by vascular disease (DM: glucose ➝ sorbitol) due to  diffusion of oxygen and nutrients to
interior (middle) fibers from compromised vasculature that resides on outside of nerve.
 Signs: ptosis, "down-and-out" gaze.
o Parasympathetic output
 fibers on the periphery are first affected by compression (e.g., PCom aneurysm, uncal herniation).
 Signs: diminished or absent pupillary light reflex, "blown pupil" often with "down-and-out" gaze A .
 CN IV palsy/damage
o Pupil is higher in the affected eye B .
o Characteristic head tilt to contralateral/ unaffected side to compensate for lack of intorsion in affected eye.
o Can't see the floor with CN IV damage (eg, difficulty going down stairs, reading).
 CN VI palsy/damage ➝ Affected eye unable to abduct C and is displaced medially in primary position of gaze.

 Internuclear Ophthalmoplegia
o Medial longitudinal fasciculus (MLF in MS):
 pair of tracts that interconnect CN VI and CN III nuclei.
 Coordinates both eyes to move in same horizontal direction.
 Highly myelinated (must communicate quickly so eyes move at same time).
 Lesions may be unilateral or bilateral (latter classically seen in multiple sclerosis, stroke).
 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 displays nystagmus (CN VI overfires to stimulate CN III). Convergence normal.
 MLF in MS
 When looking left, left nucleus of CN VI fires, which contracts the left lateral rectus and stimulates the
contralateral (right) nucleus of CN III via the right MLF to contract the right medial rectus.
 Directional term (eg, right INO, left INO) refers to the eye that is unable to adduct.
 INO = Ipsilateral adduction failure, Nystagmus Opposite.

 Visual Field Defects
1. Right anopia (monocular vision loss)
2. Bitemporal hemianopia (pituitary lesion, chiasm)
3. Left homonymous hemianopia
4. Left upper quadrantanopia (right temporal lesion, MCA)
5. Left lower quadrantanopia (right parietal lesion, MCA)
6. Left hemianopia with macular sparing (right occipital lesion, PCA)
7. Central scotoma (eg, macular degeneration)
o Ventral optic radiation (Meyer loop)—lower retina; loops around inferior horn of lateral ventricle.
o Dorsal optic radiation—superior retina; takes shortest path via internal capsule.
 Cavernous Sinus
o Collection of venous sinuses either side of pituitary.
o Blood from eye and superficial cortex ➝ cavernous sinus ➝ internal jugular vein.
o CN 3, 4, 6, V2, VI + postganglionic sympathetic pupillary fibers en route to orbit all pass-through cavernous sinus.
o Cavernous portion of internal carotid artery is also here.
o Cavernous sinus syndrome
 presentations
 variable ophthalmoplegia (eg, CN III and CN VI),
  corneal sensation,
 Horner syndrome
 occasional  maxillary sensation.
 2° to pituitary tumor mass effect, carotid-cavernous fistula, or cavernous sinus thrombosis related to
infection (spread due to lack of valves in dural venous sinuses).










 A
