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USMLE STEP 1 Neurology

Terms in this set (411)

The notochord induces what to differentiate into what?

Induces overlying ECTODERM to differentiate into NEUROECTODERM and form NUERAL PLATE

Neural plate then gives rise to?

Neural tube and neural crest cells

Notochord becomes what?

Nucleus pulposus of the intervertebral disks in adults

Alar Plate

Dorsal [Sensory]
Same orientation as spinal cord

Basal Plate

Ventral [Motor]
Same orientation as the spinal cord

How does FGF affect chordin and noggin?

FGF regulates chordin and noggin to down regulate BMP which leads to neural plate induction

Three Primary Vesicles

1. Forebrain [Prosencephalon]
2. Midbrain [Mesencephalon]
3. Hindbrain [Rhombencphaln]

The Forebrain gives rise to:

1. Telencephalon [Cerebral hemispheres, lateral ventricles]
2. Diencephalon [Thalamus, Third Ventricle]

The Midbrain gives rise to:

1. Mesencephalon [Midbrain, aqueduct]

The Hindbrain gives rise to:

1. Metencephalon [Pons, cerebellum, upper part of the fourth ventricle]
2. Myelencephalon [Medulla, Lower part of the fourth ventricle]

CNS/PNS Origins

Neuroectoderm = CNS neurons, ependymal cell [Inner lining of ventricles, makes CSF], oligodendrocytes, astrocytes
Neural crest cells = PNS, schwann cells
Mesoderm = Microglia [Like Macrophages, originate from Mesoderm]

Neural tube defects

NEUROPORES fail to fuse [4th week] → Persistent connection between amniotic cavity and spinal canal
Associated with:
1. Low folate levels before conception and during pregnancy
2. ↑ a-fetoprotein levels [AFP] in amniotic and maternal serum
3. ↑ AChE in amniotic fluid [Helpful confirmatory test]
-- Fetal AChe in CSF transudates across defect into amniotic fluid

Spina bifida occulta

Failure of bony spinal canal to close, NO STRUCTURAL HERNIATION
Usually seen at lower vertebral levels
DURA INTACT
Associated w/ tuft of hair or skin dimple at level of bony defect
NORMAL AFP

Meningocele

Meninges [BUT NO NEURAL TISSUES] herniates through bony defect

Meningomyelocele

Meninges and neural tissue herniate through bony defect
Associated w/ Arnold-Chiari Type II Malformation

Anencephaly

Malformation of the ANTERIOR NEURAL TUBE →
1. No forebrain
2. Open calvarium
Clinical Findings:
1. ↑ a-fetoprotein levels [AFP]
2. Polyhydramnios [No swallowing center in brain]
3. Associated w/ MATERNAL TYPE I DIABETES
4. Maternal folate supplementation ↓ risk

Holoprosencephaly

Failure of LEFT AND RIGHT HEMISPHERES TO SEPARATE
Usually occurs during the 5th and 6th week
May be related to mutations in the SONIC HEDGEHOG signaling pathway
Moderate form = Cleft lip/palate
Severe form = Cyclopia
Seen in:
1. PATAU SYNDROME
2. FETAL ALCOHOL SYNDROME

Chiari Type II Malformation

Posterior fossa malformation
Significant HERNIATION of the CEREBELLAR TONSILS and VERMIS through FORAMEN MAGNUM with AQUEDUCTAL STENOSIS and HYDROCEPHALUS
Patients often present w/:
1. Lumbosacral meningomyelocele
2. Paralysis below the defect

Dandy-Walker Malformation

AGENESIS of CEREBELLAR VERMIS with CYSTIC ENLARGEMENT of the 4th ventricle
Fills enlarged posterior fossa
Associated w/:
1. Hydrocephalus
2. Spina bifida

Syringomyelia

Cystic cavity [Syrinx] within SPINAL CORD
If central canal = Hydromyelia
Crossing anterior spinal commissural fibers are typically damaged
CAPE-LIKE BILATERAL LOSS OF PAIN and TEMPERATURE in the UPPER EXTREMITIES
Fine touch sensation is preserved
Associated w/:
1. Arnold Chiari malformation
2. Trauma
3. Tumor
Most common C8-T1 [CERVICAL ENLARGEMENT]

Arnold Chiari Type I Malformation

CEREBELLAR TONSILLAR ECTOPIA > 3-5 mm
Congenital
Usually asymptomatic in childhood
Manifests w/ HEADACHE and CEREBELLAR SYMPTOMS

Which arches form the anterior 2/3rds of the tongue

1st and 2nd brachial arches
-- Sensation via CN V
-- Taste via CN VII

Which arches form the posterior 1/3rd of the tongue

3rd and 4th brachial arches
--Sensation and taste via CN IX
-- Extreme posterior vagus

Motor innervation of the tongue

CN XII [Hypoglossal nerve] to:
1. Hyoglossus = Retracts and depresses tongue
2. Genioglossus = Protrudes tongue
3. Styloglossus = Draws sides of tongue upward to create a trough for swallowing
CN X [Vagus] to:
1. Palatoglossus = Elevates posterior tongue during swallowing

Neurons

Signal-transmitting cells of the nervous system
Permanent cells = DO NOT DIVIDE IN ADULTHOOD
Signal relaying cells w/ dendrites [Receive input], cell bodies, and axons [Send output]

CELL BODIES AND DENDRITES CAN BE SEEN ON NISSLE STAINING [Stains RER]

RER is not present in an axon

Loss of Nissle substance indicates

Irreversible hypoxic damage = Red neuron

Injury to axon results in what?

Wallerian degeneration →
1. Degeneration distal to the injury
2. Axonal retraction proximally
3. Allows for regeneration of axon [If in PNS]

Astrocytes

Functions:
1. Physical support
2. Repair
3. K+ metabolism
4. Removal of excess neurotransmitter
5. Component of the blood brain barrier via foot process interaction w/ perivascular space
6. Glycogen fuel reserve buffer
7. Reactive gliosis in response to neural injury
8. DERIVED FROM NEUROECTODERM

Astrocyte Marker

GFAP

Microglia

Phagocytic scavenger cells of CNS [Mesodermal, mononuclear origin]
Activated in response to tissue damage
NOT READILY DISCERNIBLE BY NISSL stain

HIV-INFECTED MICROGLIA FUSE TO FORM MULTINUCLEATED GIANT CELLS IN CNS

Myelin

↑ Conduction velocity of signals transmitted down axons → Saltatory conduction of action potential at nodes of Ranvier [HIGH CONCENTRATIONS of Na+ channels]

CNS = Oligodendrocyte [Single sheath, 50 axons]
PNS = Schwann cells [Single sheath, single axon]

Wraps and insulates axons
↑ Space constant and ↑ Conduction velocity

Schwann cells

Each Schwann cells myelinates only 1 PNS aon
Also promotes axonal regeneration
Derived from NEURAL CREST
↑ Conduction velocity of signals transmitted down axons → Saltatory conduction of action potential at nodes of Ranvier [HIGH CONCENTRATIONS of Na+ channels]

May be INJURED IN GUILLAIN-BARRE SYNDROME

Acoustic Schwannoma

Typically located in the internal acoustic meatus [CN VIII]
If BILATERAL, strongly associated with NEUROFIBROMATOSIS TYPE 2

Oligodendroglia

Myelinated axons of neurons in CNS
Each oligodendrocyte can myelinate ~30 axons
PREDOMINANT TYPE OF GLIAL CELL IN WHITE MATTER
Derived from NEUROECTODERM
FRIED EGG appearance histologically

Injured in:
1. Multiple Sclerosis
2. Multifocal progressive leukoencephalopathy [PML]
3. Leukodystrophies

Free nerve endings

C = Slow, unmyelinated fibers
Aδ = Fast, myelinated fibers

Location: All skin, epidermis, some viscera
Sense: Pain, temperature

Meissner Corpuscles

Large myelinated fibers, adapt quickly
Location: Glabrous [Hairless] skin
Senses: Dynamic, light touch/position sense

Pacinian Corpuscles

Large, myelinated fibers, adapt quickly
Location: Deep skin layers, ligaments, joints
Senses: Vibration, pressure

Merkel Discs

Large, myelinated fibers, adapt quickly
Location: Fingertips, superficial skin
Senses: Pressure, deep static touch [Shapes, edges], position sense

Ruffini Corpuscles

Dendritic endings w/ CAPSULE
ADAPT SLOWLY
Location: Fingertips and joints
Senses: Pressure, slippage of objects along surface of skin, joint angle change

Endoneurium

Invests single nerve fiber layers [INFLAMMATORY INFILTRATE IN GUILLAIN BARRE SYNDROME]
Inner

Perineurium

PERMEABILITY BARRIER
Surrounds fascicle of nerve fibers
MUST BE REJOINED IN MICROSURGERY FOR LIMB REATTACHMENT
Around

Epineurium

Dense connective tissue that surrounds entire nerve [Fascicles and blood vessels]
Epi = Outer

Norepinephrine

↑ Anxiety
↓ Depression
Location: Locus coeruleus [Pons] = Stress and Panic

Dopamine

↑ Huntington's Disease
↓ Parkinson's Disease
↓ Depression
Location: Ventral tegmentum and substantia nigra pars compacta [Midbrain]

5-HT [Serotonin]

↓ Anxiety
↓ Depression
Location: Raphe nuclei [Pons, medulla, midbrain]

ACh

↑ Parkinson's Disease
↓ Alzheimer's Disease
↓ Huntington's disease
Location: Basal nucleus of Meynert

GABA

↓ Anxiety
↓ Huntington Disease
Location: Nucleus Accumbens = Reward center, pleasure, addiction, fear

Blood brain barrier

Prevents circulating substances [Bacteria and blood] from reaching the CSF/CNS
Formed by 3 structures:
1. Tight Junctions between nonfenestrated capillary endothelial cells
2. Basement membrane
3. Astrocyte foot processes

Glucose and amino acids cross slowly by CARRIER-MEDIATED transport mechanisms

NONPOLAR/LIPID-Soluble cross rapidly via diffusion

Specialized brain regions w/ fenestrated capillaries and no blood brain barrier

Allow molecules in blood to affect brain function
1. Area postrema = Vomiting after chemo
2. OVLT = Osmotic sensing
Or neurosecretory products to enter circulation
1. Neurohypophysis = ADH release

Infarction and/or neoplas destroys what to cause vasogenic edema?

Endothelial tight junction → vasogenic edema

Blood barriers:

1. Blood brain barrier
2. Blood testis barrier
3. Maternal-fetal blood barrier of placenta

Hypothalamus

Wears TAN HATS
1. Thirst and water balance
2. Adenohypophysis control [Regulates anterior pituitary]
3. Neurohypophysis [Releases hormones in hypothalamus]
4. Hunger
5. Autonomic regulation
6. Temperature
7. Sexual urges

Inputs [AREAS NOT PROTECTED BY BBB]
1. OVLT = Organum vasculosum of the lamina terminalis
-- Senses changes in osmolality
2. Area Postrema [Responds to emetics]

Vasopressin [ADH] is produced where?

Supraoptic nucleus of the hypothalamus

Oxytocin is produced where?

Paraventricular nucleus

Lateral Area of the Hypothalamus

1. Hunger
2. Destruction → Anorexia, failure to thrive
3. INHIBITED BY LEPTIN
If you zap your lateral, you shrink laterally

Ventromedial Area of the Hypothalamus

1. Satiety
2. Destruction [Craniopharyngioma] → Hyperphagia
3. STIMULATED BY LEPTIN

Anterior Hypothalamus

Cooling, parasympathetic
A/C = Anterior, cooling

Posterior Hypothalamus

Heating, sympathetic
If you zap your Posterior hypothalamus, you become a Poikilothermic [Cold-blooded, like a snake]

Suprachiasmatic Nucleus

CIRCADIAN RHYTHMS
You sleep to be charismatic

Sleep cycle is regulated by what?

Sleep cycle is regulated by the circadian rhythm [Driven by the suprachiasmatic nucleus of the hypothalamus]

SCN is regulated by the environment [Light]

Circadian rhythms control nocturnal release of what?

1. ACTH
2. Prolactin
3. Melatonin
4. Norepinephrine

SCN → Norepinephrine release → Pineal Gland → Melatonin

Two Stages of Sleep:

1. Rapid-eye movement [REM] and non-REM
-- Extraocular movements during REM sleep due to activity of the PPRF [Paramedian pontine reticular formation/conjugate gaze center]
-- Occurs every 90 minutes, duration ↑ throughout the night

At night, BATS, Drink Blood
Awake [Eyes open] = Beta
Awake [Eyes closed] = Alpha
Non-REM N1 =Theta
Non-REM N2 = Spindle and K complex
Non-REM N3 = Delta
REM = Beta

What is associated w/ ↓ REM sleep and delta wave sleep?

1. Alcohol
2. Benzodiazepines
3. Barbiturates
4. Norepinephrine

Treatment for bedwetting [Enuresis]

Oral desmopressin [ADH analog]
Preferred over imipramine [Due to adverse effects]

Treatment for night terrors and sleep-walking

Benzodiazepine

Awake [Eye's open]

Alert, active mental concentration
Beta [Highest frequency, lowest amplitude]

Awake [Eye's closed]

Alpha waves

Non-REM Sleep: Stage N1 [5%]

Light sleep
Theta waves

Non-REM Sleep: Stage N2 [45%]

Deeper sleep, when bruxism occurs
Sleep spindles and K complexes

Non-REM Sleep: Stage N3 [25%]

Deepest non-REM sleep [Slow-wave sleep]
When:
1. Sleepwalking
2. Night Terrors
3. Bedwetting occurs
Delta wave [Lowest frequency, highest amplitude]

REM Sleep [25%]

1. LOSS OF MOTOR TONE
2. ↑ Brain O2 use
3. ↑ Variable pulse and pressure
4. When dreaming and penile/clitoral tumescence occurs
5. May serve memory processing function

Beta wave

Thalamus

Major relay for all ascending sensory information [EXCEPT OLFACTION]

VPL of Thalamus

1. Spinothalamic and dorsal columns/medial lemniscus
INFO: Pain, temperature, touch, vibration, proprioception
Destination: 1° Somatosensory cortex

VPM of Thalamus

1. Trigeminal and gustatory pathway
INFO: Face sensation, taste
Destination: 1° somatosensory cortex
Notes: Makeup goes on the face

LGN of Thalamus

1. CN II
INFO: Vision
Destination: Calcarine sulcus
Lateral = Light

MGN of Thalamus

1. Superior olive and inferior colliculus of tectum
INFO: Hearing
Destination: Auditory cortex of temporal lobe
Medial = Music

VL of Thalamus

1. Basal ganglia, cerebellum
INFO: Motor
Destination: Motor cortex

Limbic System

Collection of neural structures involved in
1. Emotion
2. Long-term memory
3. Olfactory
4. Behavior modification
5. ANS function

STRUCTURES:
1. Hippocampus
2. Amygdala
3. Fornix
4. Mammillary bodies
5. Cingulate gyrus

RESPONSIBLE FOR [5 F's]:
1. Feeding
2. Fleeing
3. Fightin
4. Feeling
5. Sex

Osmotic Demyelination Syndrome [Central pontine myelinolysis]

Clinical Manifestations:
1. Acute paralysis
2. Dysarthria
3. Dysphagia
4. Diplopia
5. LOC
6. Can cause locked-in syndrome

MASSIVE AXONAL DEMYELINATION IN PONTINE WHITE MATTER
2° to osmotic changes [Commonly iatrogenic, can be due to overly rapid correction of hyponatremia]
-- Results in cerebral edema/herniation

Correcting serum Na+ too fast:
1. From low to high, your pons will die! [Osmotic Demyelination Syndrome]
2. From high to low, your brains will blow! [Cerebral edema/herniation]

Cerebellum

Modulates movement, aids in coordination and balance
Input:
1. Contralateral cortex via middle cerebellar peduncle
2. Ipsilateral proprIoceptive Information via Inferior cerebellar peduncle from spInal cord
Output:
1. Sends information to the contralateral cortex to modulate movement
-- Output nerves = Purkinje cells → Deep nuclei of the cerebellum → Contralateral cortex via superior cerebellar peduncle

Deep nuclei [Lateral to medial] = Don't Eat Greasy Foods
1. Dentate
2. Emboliform
3. Globose
4. Fastigial

Lateral Lesions to the Cerebellum

Voluntary movement of extremities
PROPENSITY TO FALL TOWARD IPSILATERAL SIDE

Medial Lesions to the Cerebellum

Lesions involving midline structures [Vermal cortex, fastigial nuclei] and/or flocculonodular lobe →
1. Truncal ataxia [Wide-based cerebellar gait]
2. Nystagmus
3. Head tilting
4. Generally, midline lesions result in BILATERAL MOTOR DEFICITS affect AXIAL and PROXIMAL LIMB MUSCULATURE

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]
Lentiform = Putamen + Globus pallidus

D1 receptor = DIrect pathway
Indirect = Inhibitory

Excitatory pathway in the basal ganglia

Cortical inputs stimulate striatum, stimulating release of GABA [Disinhibits the thalamus via the GPi/SNr] = ↑ Motion

Inhibitory pathway in the basal ganglia

Cortical inputs stimulate the striatum [Disinhibits STN via GPe, STN stimulates GPi/SNr to inhibit thalamus] = ↓ Motion

Dopamine binds to what in the basal ganglia

D1 receptors stimulating the excitatory [Direct pathways]
D2 inhibiting the inhibitory pathway → ↑ Motion

Athetosis

Slow, writhing movements, ESPECIALLY SEEN IN FINGERS
Locations of Lesion: Basal ganglia [Huntington]

WRITHING, SNAKE-LIKE MOVEMENT

Chorea

Sudden, jerky, purposeless movements
Location of Lesion: Basal ganglia [Huntington]

CHOREA = Dance-like

Dystonia

Sudden, involuntary muscle contractions

Example: Writer's cramp
Blepharospasm [Sustained eye twitch]

Essential Tremor

HIGH-FREQUENCY tremor w/ SUSTAINED POSTURE [Outstretched arms], WORSENED w/ MOVEMENT
Often familial
Patient's often self-mediate w/ EtOH = ↓ Tremor amplitude

Treatment: B-blockers, Primidone

Hemiballismus

Sudden, wild flingin of 1 arm +/- IPSILATERAL LEG
Location: CONTRALATERAL subthalamic nucleus [Lacunar stroke]

Intention Tremor

Slow zigzag motion when pointing/extending toward target
Location: Cerebral dysfunction

Myoclonus

Sudden, brief, uncontrolled muscle contraction
JERK
HICCUPS common in metabolic abnormalities such as renal and liver failure

Resting tremor

Uncontrolled movement of distal appendages [Most appreciable in hands]
Tumor ALLEVIATED BY INTENTIONAL MOVEMENT
Example: Parkinson's disease [Pill-rolling tremor]

Parkinson's Disease

Degenerative disorder of CNS associated w/ LEWY BODIES [Composed of a-synuclein = Intracellular eosinophilic inclusions] and LOSS OF DOPAMINERGIC NEURONS [Depigmentation] of substantia nigra pars compacta
Parkinson TRAPS your body:
1. Tremor [Pill-rolling tremor at rest
2. Rigidity
3. Akinesia [or bradykinesia]
4. Postural instability
5. Shuffling gait

Huntington's Disease

AUTOSOMAL DOMINANT
Trinucleotide repeat on chromosome 4 [CAG repeats]
-- Caudate loses ACh and GABA
Symptoms manifest between ages 20-50
Clinical Manifestations:
1. Choreiform movements
2. Aggression
3. Depression
4. Dementia [Sometimes mistaken for substance abuse]

Labs:
1. ↑ Dopamine
2. ↓ ACh
3. ↓ GABA

Neuronal cell death via NMDA-R binding and GLUTAMATE TOXICITY

ATROPHY OF CAUDATE NUCLEI w/ ex vacuo DILATION OF FRONTAL HORNS

Cerebral Cortex

Aphasia

Higher-order inability to speak [Language deficit]

Dysarthria

Motor inability to speak [Movement deficit]

Broca's Area

NONFLUENT aphasia
Intact comprehension with IMPAIRED REPETITION
INFERIOR FRONTAL GYRUS OF FRONTAL LOBE

Wernicke' Area

FLUENT aphasia with IMPAIRED COMPREHENSION and REPETITION
SUPERIOR TEMPORAL GYRUS OF TEMPORAL LOBE
Wernick is Wordy but makes no sense

Conduction Aphasia

Poor repetition but fluent speech, INTACT COMPREHENSION
Caused by damage to the arcuate fasciculus
Can't repeat phrases like "NO, IFS, ANDS, or BUTS"

Global

NONFLUENT APHASIA WITH IMPAIRED COMPREHENSION
Arcuate fasciculus, Broca's, and Wernicke's areas affected

Transcortical motor

Nonfluent aphasia with good comprehension and intact repetition

Transcortical sensory

Poor comprehension with fluent speech and intact repetition

Mixed transcortical

Nonfluent speech, poor comprehension, INTACT REPEPTITON

Amygdala Lesion [Bilateral]

Kluver-Bucy Syndrome = Disinhibited behavior [Hyperphagia, hypersexuality, hyperorality]
Associated w/ HSV-1

Frontal lobe Lesion

Disinhibition and deficits in concentration, orientation, judgement
May have a reemergence of primitive reflexes

Nondominant parietal-temporal cortex Lesion

HEMISPATIAL NEGLECT [Agnosia of the contralateral side of the world]

Dominant parietal-temporal cortex Lesion

1. Agraphia
2. Acalculia
3. Finger agnosia
4. Left-right disorientation
GESTERMANN SYNDROME

Reticular Activating System [Midbrain] Lesion

Reduced levels of arousal and wakefulness [Coma]

Mammillary Bodies [Bilateral] Lesion

Wernicke-Korsakoff Syndrome
1. Confusion
2. Ophthalmoplegia
3. Ataxia
4. Memory loss [Anterograde and retrograde amnesia]
5. Confabulation
6. Personality changes

Associated w/ B1 [Thiamine] Deficiency and excessive EtOH use
Can be precipitated by GLUCOSE w/out B1 to a B1-deficient patient
Wernicke problems in a can of beer:
1. Confusion
2. Ataxia
3. Nystagmus

Basal Ganglia Lesion

May result in a tremor at rest, chorea, athetosis
Parkinson's Disease
Huntington's Disease

Cerebellar Hemisphere Lesion

1. Intention tremor
2. Limb ataxia
3. Loss of balance
4. Damage to cerebellum → Ipsilateral deficits
FALL TOWARD THE SIDE OF THE LESION

Cerebellar hemispheres are LATERALLY LOCATED and affect the LATERAL LIMBS

Cerebellar Vermis Lesion

1. Truncal ataxia
2. Dysarthria
Vermis is CENTRALLY LOCATION affects the CENTRAL LIMBs

Subthalamic Nucleus Lesion

CONTRALATERAL hemiballismus

Hippocampus [Bilateral]

Anterograde amnesia = Inability to make new memories

Paramedian Pontine Reticular Formation

Eyes look away from the side of lesion

Frontal Eye fields

Eyes look toward the side of the lesion

Watershed Zones

Between
1. Anterior/middle cerebral
2. Posterior/Middle cerebral

DAMAGE IN SEVERE HYPOTENSION
1. Upper arm/leg weakness
2. Defects in higher-order visual processing

Anterior Cerebral Artery

Homunculus

Topographic representation of motor and sensory areas in cerebral cortex
Distorted image is due to certain body regions being more richly innervated and thus having ↑ cortical representations

Regulation of cerebral perfusion

Brain perfusion relies on tight autoregulation
Cerebral perfusion is mostly driven by PCO2 [PO2 modulates perfusion in severe hypoxia]
Therapeutic hyperventilation [↓ PCO2], helps ↓ ICP in cases of
1. Acute cerebral edema [Stroke, trauma] via vasoconstriction

Fainting in panic attacks due to ↓ perfusion

Hypoxemia and cerebral perfusion

↑ cerebral perfusion pressure only when PO2 < 5o mmHg

Cerebral perfusion pressure is proportional to what

Cerebral perfusion pressure is proportional to PCO2 until PCO2 > 90 mmHg

Cerebral perfusion and blood pressure

Cerebral perfusion lies on pressure gradient between mean arterial pressure [MAP] and ICP
↓ blood pressure or ↑ ICP → ↓ Cerebral perfusion pressure [CPP]

CPP = MAP - ICP
If CPP = 0, there is not cerebral perfusion → Brain death

MCA Lesion

1. Motor cortex = Upper limb and face [Contralateral paralysis]
2. Sensory cortex = Upper limb and face [Contralateral loss of sensation]
3. Temporal lobe = Wernicke Area
4. Frontal lobe = Broca's Area
APHASIA IF IN DOMINANT [Usually left hemisphere]
HEMINEGLECT IF IN NONDOMINANT [Usually right hemisphere]

ACA Lesion

1. Motor cortex = Lower limb [Contralateral paralysis]
2. Sensory cortex = Lower limb [Contralateral loss of sensation]

Lenticulostriate Artery Lesion

Striatum [Putamen = Motor, Caudate = Cognitive, Internal capsule
Contralateral hemiparesis/hemiplegia

COMMON LOCATION OF LACUNAR INFARCTS, 2° to unmanaged hypertension

Anterior Spinal [ASA]

1. Lateral corticospinal tract = Contralateral hemiparesis [Upper and lower limbs]
2. Medial lemniscus = ↓ Contralateral proprioception
3. Caudal medulla = Hypoglossal nerve [Ipsilateral hypoglossal dysfunction = Tongue licks the lesion]

STROKE COMMONLY BILATERAL

Medial Medullary Syndrome

Caused by infarct of paramedian branches of ASA and vertebral arteries

PICA Lesion

1. Lateral medulla
-- Vestibular Nuclei
-- Lateral Spinothalamic tract
-- Spinal trigeminal nucleus
-- Nucleus ambiguus
-- Sympathetic fibers
-- Inferior cerebellar peduncle [Proprioceptive information]

Clinical Manifestations:
1. Vomiting
2. Vertigo
3. Nystagmus
4. ↓ Pain and temperature sensation from IPSILATERAL FACE and CONTRALATERAL BODY
5. DYSPHAGIA
6. HOARSENESS
7. ↓ Gag reflex
8. Ipsilateral horner syndrome
9. Ataxia
10. Dysmetria

Lateral Medullary [Wallenberg Syndrome] Lesion

Nucleus ambiguus effects are SPECIFIC TO PICA lesion
"Don't PICA Horse [Hoarseness] that can't eat [Dysphasia]

ACA

LATERAL PONS
1. Cranial facial nerve
2. Vestibular nuclei
3. Facial nuclei
4. Spinal trigeminal nuclei
5. Cochlear nuclei
6. Sympathetic fibers

MIDDLE AND INFERIOR CEREBELLAR PEDUNCLES
1. Ataxia
2. Dysmetria

Clinical Manifestations:
1. Vomiting
2. Vertigo
3. Nystagmus
4. PARALYSIS OF FACE
5. ↓ Lacrimation, salivation
6. ↓ Taste from anterior 2/3rd of tongue
7. IPSILATERAL ↓ pain and temperature
8. CONTRALATERAL ↓ pain and temperature

Lateral Pontine Syndrome

Facial nucleus effects are specific to AICA lesions
FACIAL DROOP means AICA's pooped

PCA

1. Occipital cortex
2. Visual cortex [CONTRALATERAL hemianopia w/ macular sparing]

Basilar Artery

1. Pons
2. Medulla
3. Lower Midbrain
4. Corticospinal and corticobulbar tracts
5. Ocular cranial nerve nuclei
6. Paramedian pontine reticular formation

Clinical Manifestation [LOCKED IN SYNDROME]:
1. Preserved consciousness and blinking
2. Quadriplegia
3. Loss of voluntary facial, mouth, and tongue movement
4. Locked-in syndrome

Anterior Communicating Artery [ACom]

Most common lesion is ANEURYSM
Can lead to STROKE
SACCULAR [BERRY] aneurysm can impinge cranial nerves
VISUAL FIELD DEFECTS [Due to compression of the optic chiasm]
LESIONS ARE TYPICALLY ANEURYSMS, not strokes

Posterior Communicating Artery [PCom]

Common site of saccular aneurysm
CN III palsy = EYES DOWN AND OUT [Ptosis and mydriasis]
LESIONS ARE TYPICALLY ANEURYSMS NOT STROKES

Saccular [Berry] Aneurysm

Occurs at bifurcations in the CIRCLE OF WILLIS
Most common site is JUNCTION OF ANTERIOR COMMUNICATING and ANTERIOR CEREBRAL
Rupture [Most common complication] → Subarachnoid hemorrhage
*** WORST HEADACHE OF MY LIFE
Can also lead to hemorrhagic stroke

Can cause:
1. Bitemporal hemianopia via compression of optic chiasm

Associated with:
1. ADPKD
2. Ehlers-Danlos Syndrome
3. Advanced age
4. HTN
5. Smoking
6. ↑ Risk in black

Charcot-Bouchard Microaneurysm

Chronic HTN
Affects small vessels [Basal ganglia, thalamus]

Central Post-Stroke Pain Syndrome

Neuropathic pain due to THALAMIC LESIONS
Initial paresthesia followed in WEEKS TO MONTHS by
1. Allodynia [Ordinarily painless stimuli cause pain]
2. Dysesthesia
OCCURS IN 10% of STROKE PATIENTS

Epidural hematoma

Rupture of MIDDLE MENINGEAL ARTERY [Branch of the MAXILLARY]
Often 2° to fracture of temporal bone
LUCID INTERVAL
Rapid expansion under systemic arterial pressure → TRANSTENTORIAL herniation, CN III Palsy

CT show BICONVEX [Lentiform], Hyperdense blood collection
NOT CROSSING SUTURE LINES
Can cross FALX and TENTORIUM

Subdural hematoma

Rupture of BRIDGING VEINS
SLOW VENOUS BLEED [Less pressure =Hematoma develops over time]
Seen in:
1. Elderly
2. Alcoholics
3. Blunt trauma
4. SHAKEN BABY SYNDROME
[Predisposing factors = Brain atrophy, shaking, whiplash]
CRESCENT-SHAPED hemorrhage that CROSSES SUTURE LINES
MIDLINE SHIFT
Cannot cross falx, tentorium

Subarachnoid hemorrhage

Rupture of ANEURYSM [Berry/saccular aneurysm in Ehlers-Danlos and ADPKD] or ARTERIOVENOUS MALFORMATION
Rapid time course
WORST HEADACHE OF MY LIFE
Bloody or yellow spinal tap [Xanthochromia]
2-3 days afterward, risk of vasospasm due to blood breakdown [Not visible on CT, treat w/ NIMODIPINE] and rebleed [Visible on CT]

Intraparenchymal [Hypertensive] Hemorrhage

Commonly caused by SYSTEMIC HTN
Also seen w/
1. AMYLOID ANGIOPATHY [Recurrent lobar hemorrhagic stroke in elderly
2. Vasculitis
3. Neoplasm
Typically occurs in BASAL GANGLIA, INTERNAL CAPSULE [Charcot-Bouchard Aneurysm of lenticulostriate vessels]

Ischemic Brain Disease/Stroke

Irreversible damage begins after 5 minutes of hypoxia [Due to glucose dependence]
Most vulnerable:
1. Hippocampus
2. Neocortex
3. Cerebellum
4. Watershed areas

Ischemic HYPOxia = HYPOcampus most vulnerable

Stroke Imaging

Noncontrast CT to exclude hemorrhage [Before tPA can be given]
CT detects changes in 6-24 hours
Diffusion weighed MRI can detect ischemia w/in 3-30 minutes

Time since ischemia event and histologic factors

12-48 hours = Red neurons
48-72 hours = Necrosis + neutrophils
3-5 days = Macrophages [Microglia]
1-2 weeks = Reactive gliosis + vascular proliferation
> 2 weeks = Glial scar

Hemorrhagic Stroke [15%]

Intracerebral bleeding, often due to:
1. HTN
2. Anticoagulation
3. Cancer [Abnormal vessels can bleed]
May be 2° to ischemic stroke followed by reperfusion [↑ Vessel fragility]
BASAL GANGLIA ARE THE MOST COMMON SITE OF INTRACRANIAL HEMORRHAGE

Ischemic Stroke [85%]

Acute blockage of vessels → Disruption of blood flow and subsequent ischemia → LIQUEFACTIVE NECROSIS
Three Types
1. Thrombotic = Clot forms directly at site of infarction [Commonly MCA]
2. Embolic = Embolus from another part of the body obstructs vessel
-- Can affect multiple vascular territories
-- Examples: Atrial fibrillation, DVT w/ patent foramen ovale
3. Hypoxic = Hypoperfusion or hypoxemia
-- Common during CARDIOVASCULAR SURGERIES
-- TENDS TO AFFECT WATERSHED AREAS

Treatment: tPA [If w/in 3-4.5 hours of onset and no hemorrhage/risk of hemorrhage]
Reduce risk w/ medical therapy:
1. Aspirin
2. Clopidogrel
3. Optimum control of BP, blood sugars, lipids
4. Treat conditions that ↑ atrial fibrillation

Transient Ischemic Attack [TIA]

Brief, reversible episode of focal neurologic dysfunction without acute infarction [- MRI]
Majority resolves in < 15 minutes, deficits due to FOCAL ISCHEMIA

Dural Venous Sinuses

Large venous channels that run through the dura
Drain blood from cerebral veins and receive CSF from arachnoid granulation
EMPTIES INTO JUGULAR VEINS

Ventricular System

Lateral ventricle → 3rd ventricle via right and left interventricular foramen of Monro
3rd ventricle → 4th ventricle via cerebral aqueduct [of Sylvius]
4th ventricle → Subarachnoid space via
1. Formina of Luschka [Lateral]
2. Foramina of Magendie [Medial]

CSF

Is made from the ependymal cells of the choroid plexus
Reabsorbed in by subarchnoid granulation and then drains into the dural venous sinuses

Idiopathic Intracranial Hypertension [Pseudotumor cerebri]

↑ ICP with no apparent cause on imaging [No hydrocephalus, obstruction of CSF outflow]
Patients present w/:
1. Headaches
2. Diplopia [Usually from CN VI palsy]
3. Non mental status alterations
4. Papilledema [Seen on exam]

Risk factors:
1. Being a woman of child-bearing years
2. Vitamin A excess
3. DANAZOL [Synthetic steroid suppresses GnRH]

Lumbar Puncture reveals ↑ opening pressure and provides headache relief

Treatment:
1. Weight loss
2. Acetazolamide [Carbonic anhydrase inhibitor]
3. Topiramate [Anticonvulsant]
4. Invasive procedures for refractory cases [Repeat lumbar puncture, CSF shunt placement, nerve fenestration surgery]

Communicating Hydrocephalus

↓ CSF absorption by arachnoid granulations → ↑ ICP, papilledema, herniation [Arachnoid scarring post-meningitis + chronic subdural hematomas]

Normal Pressure Hydrocephalus

AFFECTS ELDERLY, idiopathic
CSF pressure elevated only EPISODICALLY
Does not result in ↑ subarchnoid space volume
EXPANSION OF VENTRICLES distorts the fibers of the CORONA RADIATA → Triad:
1. Urinary Incontinence = Wet
2. Ataxia = Wobbly
3. Cognitive Dysfunction [Sometimes reversible] = Wacky

Noncommunicating hydrocepahlus

Caused by STRUCTURAL BLOCKAGE of CSF circulation through the ventricular system [Stenosis of aqueduct of Sylvius, Colloid cyst blocking foramen of Monro]

Ex vacuo ventriculomegaly

Appearance of ↑ CSF on imaging is due to DECREASED BRAIN TISSUE [Neuronal atrophy]
1. Alzheimer's disease
2. Advanced HIV
3. PICK DISEASE
ICP is NORMAL, Triad is not seen

Spinal Nerves

There are 31 pairs of spinal nerves in total:
1. 8 cervical
2. 12 thoracic
3. 5 Lumbar
4. 5 Sacral
5. 2 coccygeal

Nerves C1-C7 exit ABOVE the corresponding vertebrae
C8 spinal nerve exits BELOW C7 and above T1
All other spinal nerves exit BELOW

Vertebral disk herniation

Nucleus pulposus [Soft central disk] herniates through annulus fibrosus [Outer ring]
Usually POSTEROLATERALLY at L4-L5, L5-S1

Spinal Cord - Lower Extent

In adults, the spinal cord extends to the lower border of L1-L2
Subarachnoid space [Which contains CSF] extends to lower border of S2 vertebrae
Lumbar puncture is usually performed at L3/L4 or L4/L5 [Level of the cauda equina]

Goal of lumbar puncture

To obtain a sample of CSF w/out damaging spinal cord
To keep the cord alive, go in between L3-L5

Spinal Cord Mnemonics

Legs [Lumbosacral] are Lateral in Lateral Corticospinal tract
Dorsal columns are organized as you are, hands at side, arms out side legs [Cuneatus outside of gracilis]

Ascending Tracts

1. Dorsal Column [Pressure, vibration, touch, proprioception]
2. Fasciculus gracilis [Lower body, legs]
3. Fasciculus cuneatus [Upper body, arms]
4. Lateral spinothalamic tract [Pain and temperature]
5. Anterior spinothalamic tract [Touch, pressure]

ASCENDING TRACTS SYNAPSE THEN CROSS

Descending Tracts of Spinal Cord

1. Lateral corticospinal tract [Voluntary motor]
2. Anterior corticospinal tract [Voluntary motor]

Dorsal Column

Ascending pressure, vibration, fine touch, proprioception

1st Order Neuron =
-- Sensory nerve endings → Cell body in dorsal root ganglion
-- Enters spinal cord, SYNAPSES IN IPSILATERAL NUCLEUS CUNEATUS OR GRACILIS → ascends ipsilaterally in dorsal column

2nd Order Neuron
-- Decussates in medulla → Ascends CONTRALATERALLY in MEDIAL LEMNISCAL → Synapses in the VPL [Thalamus]

3rd Order Neuron
Sensory cortex

Spinothalamic Tract

Ascending [Lateral] pain and temperature, [Anterior] Crude touch and pressure

1st Order Neuron =
-- Sensory nerve endings [Aδ and C Fibers]→ Cell body in dorsal root ganglion
-- Enters spinal cord, SYNAPSES IN IPSILATERAL GRAY MATTER [Spinal cord] →

2nd Order Neuron
-- Decussates at ANTERIOR WHITE COMMISSURE → Ascends CONTRALATERALLY → Synapses in the VPL [Thalamus]

3rd Order Neuron
Sensory cortex

Lateral Corticospinal Tract

Descending, Voluntary movement of contralateral limbs

UMN: Cell body in 1° motor cortex → Descends ipsilaterally through INTERNAL CAPSULE, most fibers decussate at CAUDAL MEDULLA [Pyramidal decussation] → Descends CONTRALATERALLY

1st Synapse:
1. Cell body of ANTERIOR HORN

LMN: Leaves spinal cord

Synapse II: NMJ

UMN Lesions Signs

Clinical Manifestations:
1. Weakness
2. Hyperreflexia
3. Hypertonia
4. Positive Babinski [Normal in infants]
5. SPASTIC paralysis
6. CLASP KNIFE SPASTICITY

Upper MN = Everything up [Tone, DTR, toes]

LMN Lesion Signs

Clinical Manifestations:
1. Weakness
2. Hyporeflexia
3. Hypotonia
4. Atrophy
5. Fasciculations [Muscle twitching]
6. FLACCID paralysis

Lower MN = Everything lowered [Tone, DTR, toes]

Werdnig Hoffman Disease

Poliomyelitis and spinal muscular atrophy
LMN lesions only [Due to destruction of anterior horns]
FLACCID PARALYSIS

Multiple Sclerosis

Due to demyelination
MOSTLY WHITE MATTER OF CERVICAL REGION
Random and ASYMMETRIC lesions due to demyelination
Clinical Manifestations:
1. Scanning speech
2. Intention tremor
3. Nystagmus

Amyotrophic Lateral Sclerosis [ALS]

Combined UMN and LMN deficits with NO SENSORY LOSS or oculomotor deficits
Can be caused by SUPEROXIDE DISMUTASE 1 defect

Clinical Manifestations:
1. Commonly presents as fasciculations with eventual ATROPHY AND WEAKNESS OF HANDS
2. Fatal
3. Riluzole treatment modestly ↑ survival by ↓ presynaptic glutamate release
Lou Gehrig disease = Give RiLOUzole [Glutamate antagonist]

Complete Occlusion of Anterior Spinal Artery

SPARES DORSAL COLUMN and LISSAUER TRACT
Upper thoracic ASA territory is WATERSHED AREA
Artery of Adamkiewicz supplies ASA below T8

Tabes Dorsalis

Caused by 3° Syphilis
Results from degeneration [Demyelination] of DORSAL COLUMNS and roots →
1. Impaired sensation and proprioception
2. Progressive sensory ataxia [Inability to sense or feel legs → poor coordination]
Associated w/
1. Charcot joints
2. Shooting pain
3. Argyll Robertson pupil
4. ABSENCE OF DTRs and + Romberg Sign

Syringomyelia

Sprinx expands and damages ANTERIOR WHITE COMMISSURE of SPINOTHALAMIC TRACT [2nd order neurons]
1. Bilateral loss of pain and temperature [C8-T1]
2. Seen in Chiari Type I Malformation
3. Can expand and affect other tracts

Vitamin B12 Deficiency

Subacute Combine Degeneration
Demyelination of DORSAL COLUMNS, LATERAL CORTICOSPINAL TRACTS, and SPINOCEREBELLAR TRACTS
1. Gait ataxia
2. Paresthesia
3. Impaired position and vibration sense

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]

Symptoms [LMN Signs]
1. Weakness
2. Hypotonia
3. Flaccid paralysis
4. Fasciculations
5. Hyporeflexia
6. Muscle atrophy
7. Signs of infection [Malaise, headache, fever, nausea]

Findings:
1. CSF w/ ↑ WBC and slight ↑ protein [NO CHANGE IN CSF GLUCOSE]
2. Virus recovered from throat or stool

Spinal Muscular Atrophy [Werdnig-Hoffman Disease]

Congential degeneration of anterior horns of spinal cord → LMN
FLOPPY BABY w/ marked hypotonia and TONGUE FASCICULATIONS
Infantile type has median age of death at 7 months
AUTOSOMAL RECESSIVE INHERITANCE

Friedrich Ataxia

AUTOSOMAL RECESSIVE Trinucleotide repeat [GAA] on chromosome 9 in the gene that encodes FRATAXIN [Iron binding protein]
Leads to MITOCHONDRIAL DYSFUNCTION
Degeneration of multiple spinal tracts
1. Muscle weakness
2. Loss of DTRs, vibratory sense, proprioception
3. STAGGERING GAIT
4. FREQUENT FALLING
5. Nystagmus
6. Dysarthria
7. Pes Cavus
8. Hammer toes
9. DIABETES MELLITUS, HYPERTROPHIC CARDIOMYOPATHY [Cause of death]
10. Presents in childhood w/ KYPHOSCOLIOSIS

Brown-Sequard Syndrome

Hemisection of spinal cord
Findings:
1. Ipsilateral UMN signs BELOW level of lesion
2. Ipsilateral loss of tactile, vibration, proprioception sense BELOW level of lesion [Due to dorsal column damage]
3. CONTRALATERAL pain and temperature loss below level of lesion [Loss of spinothalamic]
4. Ipsilateral loss of ALL SENSATION AT LEVEL OF LESION
5. Ipsilateral LMN signs

IF lesion occurs ABOVE T1 = PATIENT WILL PRESENT WITH HORNER SYNDROME [Due to damage of the oculosympathetic pathway]

Landmark Dermatomes: C2

Posterior half of skull [ca]

Landmark Dermatome: C3

High turtleneck shirt

Landmark Dermatome: C4

Low collar shirt

Landmark Dermatome: T4

At the nippel [The Teat pore]

Landmark Dermatome: T7

Xiphoid Process

Landmark Dermatome: T10

At the umbilicus [Important for early appendicitis pain referral]
T10 at the belly butTEN

Landmark Dermatome: L1

Inguinal ligament
LI =Inguinal Ligament

Landmark Dermatome: L4

Included kneecap
Down on ALL 4's

S2, S3, S4

Erection and sensation of the penis
S2, S3, S4 Keeps the penis off the floor

S1, S2

Buckle my shoe [Achilles tendon reflex]

L3. L4

Kick the door [Patellar reflex]

C5, C6

Pick up sticks [Biceps reflex]

C7, C8

Lay them straight [Triceps reflex]

L1, L2

Testicles move [Cremaster reflex]

S3, S4

Winks galore [Anal wink reflex]

Primitive Reflexes

CNS reflexes that are present in healthy infant, but are absent in neurologically intact adult
Normally disappear w/in the first year of life
Primitive reflexes are inhibited by a mature developing frontal lobe
May reemerge in an adult following FRONTAL LOBE LESIONS → Of inhibition of this reflex

Moro Reflex

"Hanging on for life" Reflex = Abduct/Extend when startled, then draw together

Rooting Reflex

Movement of head toward side of cheek if mouth or cheek is stroked [Nipple seeking]

Suckling Reflex

Sucking response when roof of mouth is touched

Palmar Reflex

Curling of fingers if palms are stroked

Plantar Reflex

DORSIFLEXION of large toe and FANNING OF OTHER TOES upon plantar stimulation
Babinski sign - Presence of this reflex in an adult, may signify an UML

Galant Reflex

Stroking along one side of the spine while newborn is in a ventral position [Face down] causes LATERAL FLEXION OF LOWER BODY TOWARD STIMULATED SIDE

CN nuclei that lie medially

III, IV, VI, XII "Factors of 12, except 1 and 2"

Dorsal View of Brainstem

Pineal Gland = Melatonin secretion, circadian rhythms
Superior Colliculi = Conjugate vertical gaze center
Inferior Colliculus = Auditory
Your EYES are ABOVE your EARS

Parinaud Syndrome

Paralysis of the conjugate vertical gaze due to lesion in SUPERIOR COLLICULUS [Stroke, hydrocephalus, pinealoma]

Cranial Nerve Nuclei

Located in the tegmentum portion of brain stem [Between dorsal and ventral portions]
Midbrain = Nuclei CN III, IV
Pons = Nuclei CN V, VI, VII, VIII
Medulla = Nuclei CN IX, X, XII
Spinal Cord = Nucleus of CN XI

Lateral Nuclei = Sensory [aLar plate]
--- Sulcus limitans
Medial Nuclei = Motor [Basal Plate]

Cranial Nerve and Vessel Pathways: Cribriform plate

CN I

Cranial Nerve and Vessel Pathways: Middle Cranial Fossa

CN II-IV [Through sphenoid bone]
1. Optic canal = CN II, ophthalmic artery, central retinal vein
2. Superior Orbital Fissure = CN III, IV, V1, VI, ophthalmic vein, sympathetic fibers
3. Foramen Rotundum [CN V2]
4. Foramen Ovale [CN V3]
5. Foramen Spinosum [Middle Meningeal Artery]

Cranial Nerve and Vessel Pathways: Internal Auditory Meatus

CN VII, VIII

Jugular Foramen

CN IX, X, XI, jugular vein

Hypoglossal canal

CN XII

Foramen Magnum

Spinal roots of XI, brain stem, vertebral arteries

Olfactory Nerve

CN I
Smell [ONLY CN WITHOUT THALAMIC RELAY TO CORTEX]
Sensory

Optic Nerve

CN II
Sight
Sensory

Oculomotor

CN III
1. Eye movement [SR, IR, MR, IO]
2. Pupillary constriction
-- Sphincter pupillae = Edinger-Westphal nucleus, muscarinic receptors
3. Accomodation
4. Eyelid opening [Levator palpebrae
MOTOR

Trochlear

CN IV
Eye movement [SO]
Motor

Trigeminal

CN V
1. Mastication
2. Facial sensation [Ophthalmic, Maxillary, Mandibular divisions
3. Somatosensation from anterior 2/3 of tongue
BOTH

Abducens

CN VI
Eye movement [LR]
MOTOR

Facial

CN VII
1. Facial movements
2. Taste from anterior 2/3rd of tongue
3. Lacrimation, salivation [Submandibular, Sublingual glands]
4. Eye closing [Orbicularis oculi]
5. Stapedius muscle in ear [Nerve courses through parotid gland but does not innervate it]

Vestibulocochlear

CN VIII
Hearing and balance
Sensory

Glossopharyngeal

1. Taste and somatosensation from posterior 2/3 of tongue
2. Swallowing
3. Salivation [Parotid gland]
4. Monitoring carotid body and sinus chemo- and baroreceptors
5. Stylopharyngeus [Elevates pharynx, larynx]
BOTH

Vagus

CN X
1. Taste from epiglottic region
2. Swallowing
3. Soft palate elevation
4. Midline uvula
5. Talking
6. Coughing
7. Thoracoabdominal viscera
8. Monitoring aortic arch chemo- and baroreceptors
BOTH

Accessory

CN XI
1. Head turning, shoulder shrugging [SCM, trapezius]
MOTOR

Hypoglossal

CN XII
Tongue movement
MOTOR

Mnemonic for Cranial Nerves

Some Say Marry Money But My Brother Says Big Brains Matter Most

Nucleus Solitarius

Visceral SENSORY information [Taste baroreceptors, gut distension]
CN VII, IX, X

Nucleus aMbiguus

MOTOR innervation of pharynx, larynx, upper esophagus [Swallowing, palate deviation]
IX, X, XI [Cranial portion]

Dorsal Motor Nucleus

Sends autonomic [Parasympathetic] fibers to:
1. Heart
2. Lungs
3. Upper GI
CN X

Cranial Nerve Reflex; Corneal

AFFERENT: V1 [Ophthalmic nasociliary branch]
EFFERENT: VII [Temporal branch, orbicularis oculi]

Cranial Nerve Reflex: Lacrimation

AFFERENT: V1 [Loss of reflex does not preclude emotional tears]
EFFERENT: VII

Jaw Jerk Reflex

AFFERENT: V3 [Sensory - Muscle spindle from masseter]
EFFERENT: V3 [Motor - Masseter]

Pupillary Reflex

AFFERENT: CN II
EFFERENT: CN III

Gag Reflex

AFFERENT: CN IX
EFFERENT: CN X

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]
The left SCM contracts to help turn head to the right

CN XII Lesion [LMN]

Tongue deviates TOWARD SIDE of lesion [TONGUE LICKS THE LESION] due to weakened tongue muscles on affected side

Cavernosus Sinus

Collection of venous sinuses ON EITHER SIDE OF THE PITUITARY
Blood from eye and superficial cortex → Cavernous sinus → Internal jugular vein

1. CN III. IV, V1, VI and occasionally V2 plus postganglionic sympathetic pupillary fibers en route to orbit all pass through the cavernous sinus
2. Nerves that control extraocular muscles V1 and V2

CAVERNOUS PORTION OF INTERNAL CAROTID ARTERY is also here

Cavernous Sinus Syndrome

Present w/
1. Variable ophthalmoplegia
2. ↓ Corneal sensation
3. Horner Syndrome
4. Occasional ↓ maxillary sensation
5. 2° pituitary mass effect
6. Carotid-cavernous fistula
7. Cavernous sinus thrombosis related to infection

CN VI is most susceptible to injury

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
1. Malleus
2. Incus
3. Stapedius
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
Vibrations are transduced via specialized hair cells → Auditory nerve signaling → brain stem

Each frequency leads to a vibration at specific locations on the basilar membrane [Tonotopy]
1. Low frequency sounds heard at apex near helicotrema [Wide and flexible]
2. High frequency heard best at base of cochlea [Thin and rigid]

Conductive Hearing Loss

Abnormal [Bone > Air] = Localizes to affected ear

Sensorineural Hearing Loss

Normal [Air > Bone] = Localizes to unaffected ear

Noise induced

Damage to STEREOCILIATED CELLS in ORGAN OF CORTI
Loss of HIGH-FREQUENCY hearing 1st
Sudden extremely loud noises can produce hearing loss due to TYMPANIC MEMBRANE RUPTURE

Cholesteatoma

Overgrowth of DESQUAMATED KERATIN DEBRIS within MIDDLE EAR SPACE
May erode ossicles, mastoid air cells → CONDUCTIVE hearing loss

UMN Facial Lesion

Lesion of the motor cortex or connection between cortex and facial nucleus
Contralateral paralysis of lower face
FOREHEAD SPARED DUE TO BILATERAL UMN LESION

LMN Facial Lesion

IPSILATERAL paralysis of the upper and lower face

Facial Nerve Palsy

Complete destruction of the facial nucleus itself or its branchial efferent fibers [Facial nerve proper]
Peripheral ipsilateral facial paralysis [ABSENT FOREHEAD CREASES and DROOPING SMILE] with inability to close eye on involved side
Can occur idiopathically [Bell's palsy], gradual recover in most cases
Can be associated with:
1. Lyme Disease
2. Herpes Simplex [Less common]
3. Herpes Zoster [Ramsey Hunt Syndrome]
4. Sarcoidosis
5. Tumors
6. Diabetes
TREAT W/ CORTICOSTEROIDS

Mastication muscles

3 muscles close jaw [Masseter, Temporalis, Medial Pterygoid]
1 muscle opens [Lateral Pterygoid]
All are innervated by CN V, V3 [Trigeminal nerve]
M's Much
L Lowers
"It takes more to keep your mouth shut"

Normal Retina

Refractive Errors

Common cause of impaired vision, correctable with glasses

Hyperopia

Eye too SHORT for refractive power of cornea and lens → Light focused BEHIND RETINA

Myopia

Eye too LONG for refractive power of cornea and lens → Light focused in FRONT of the retina

Astigmatism

Abnormal CURVATURE of the cornea → Different refractive power at different axises

Presbyopia

AGE-RELATED impaired ACCOMMODATION [Focusing on near objects] possibly due to ↓ LENS ELASTICITY
Often necessitates reading glasses

Cataract

Painless, OFTEN BILATERAL opacification of lens →
1. ↓ Vision

Risk factors:
1. ↑ Age
2. Smoking
3. Ethanol
4. Excessive sunlight
5. Prolonged CORTICOSTEROID USE
6. CLASSIC GALACTOSEMIA
7. GALACTOKINASE DEFICIENCY
8. Diabetes mellitus [Sorbitol]
9. Trauma
10. Infection

Glaucoma

OPTIC DISK ATROPHY with characteristic CUPPING [Thinning of outer rim of optic nerve head]
Usually w/ ↑ IOP [Intraocular pressure] and PROGRESSIVE PERIPHERAL FIELD LOSS

Open Angle

Associated with:
1. ↑ Age
2. African American
3. Family hx
PAINLESS, more common in US
Primary = Cause unclear
Secondary = BLOCKED TRABECULAR MESHWORK FROM WBCS [uveitis], RBCs [Vitreous hemorrhage], retinal elements [Retinal detachment]

Closed/Narrow Angle

Primary = ENLARGEMENT of FORWARD MOVEMENT OF LENS against central iris [Pupil margin] →
1. OBSTRUCTION OF NORMAL AQUEOUS FLOW THROUGH THE PUPIL
2. Fluid builds up behind iris [Pushing peripheral iris against the cornea]
3. Impedes through through trabecular network

Secondary = HYPOXIA from retinal disease [Diabetes mellitus, vein occlusion]
-- Induces vasoproliferation in iris that contracts angle

Chronic Close/Narrow Angle Closure

Often asymptomatic with damage to optic nerve and peripheral vision

Acute Closed/Narrow Angle Closure

TRUE OPHTHALMIC EMERGENCY
↑ IOP pushes iris forward = Angle closes abruptly
1. Very PAINFUL
2. RED EYE
3. SUDDEN VISION LOSS
4. HALOS around lights
5. Rock-hard eye
6. FRONTAL HEADACHE

Do not given epinephrine b/c of its mydriatic effects

Uveitis

Inflammation of the uvea [Anterior uveitis, choroiditis/posterior uveitis]
May have
1. Hypopyon [Accumulation of pus in the anterior chamber]
2. Conjunctival redness
Associated w/ systemic inflammatory disorders:
1. Sarcoidosis
2. RA
3. Juvenile idiopathic arthritis
4. HLA-B27-associated conditions

Age-Related Macular Degeneration

Degeneration of macula [Central area of retina]
Causes:
1. Distortion [Metamorphopsia] and eventual LOSS OF CENTRAL VISION [Scotomas]

DRY [NONEXUDATIVE]
1. 80% of cases
2. Deposition of yellowish extracellular material in and beneath Bruch membrane and retinal pigment epithelium [Drusen] w/ gradual ↓ in vision
3. Prevent w/ MULTIVITAMIN and ANTIOXIDANT SUPPLEMENTS

WET [Exudative]
1. 10-15%
2. Rapid vision loss due to bleeding 2° to choroidal neovascularization
3. Treat w/ anti-VEGF injections [Ranibizumab] or laser

Diabetic Retinopathy

RETINAL DAMAGE due to chronic hyperglycemia
Two Types:
1. NONPROLIFERATIVE
--. Damaged capillaries leak blood → Lipids and fluids seep into retina
-- Hemorrhages and macular edema
-- Treatment - Blood-sugar control, macular laser
2. PROLIFERATIVE
-- Chronic hypoxia → New blood vessel formation with resultant traction on retina
-- Treatment: Peripheral retinal photocoagulation, anti-VEGF [Bevacizumab]

Retinal Vein Occlusion

Blockage of central or branch retinal vein due to COMPRESSION from nearby ARTERIAL ATHEROSCLEROSIS
Retinal hemorrhages and venous engorgement
Edema in affected areas

Retinal Detachment

Separation of NEUROSENSORY layer of retina [Photoreceptor layer w/ RODS AND CONES] from outermost pigmented epithelium [Normally shields excess light, supports retina]

Degeneration of photoreceptors → Vision loss
May be 2° to:
1. Retinal breaks
2. Diabetic traction
3. Inflammatory effusions

Visualized on fundoscopy by the splaying and paucity of retinal vessels
Correlation with cross-sectional optical ultrasound

BREAKS MORE COMMON IN PATIENTS W/ HIGH MYOPIA
-- Often preceded by posterior vitreous detachment [FLASHES and FLOATERS] and eventual monocular loss of vision
LIKE A CURTAIN BEING DRAWN DOWN

SURGICAL EMERGENCY

Central Retinal Artery Occlusion

Acute, PAINLESS, monocular vision loss
Retina CLOUDY with attenuated vessels and CHERRY RED spot on fovea [Center of macula]

Retinitis Pigmentosa

INHERITED RETINAL DEGENERATION
Painless, progressive, vision loss beginning w/ NIGHTBLINDNESS [Rods affected first]
Bone spicule-shaped deposits around macula

Retinitis

Retinal edema and necrosis leading to scar
OFTEN VIRAL [CMV, HSV, HZV]
Associated w/ IMMUNOSUPPRESSION

Papilledema

Optic disk swelling [Usually BILATERAL] due to ↑ ICP [2° to mass effect]
Enlarged BLIND SPOT and ELEVATED OPTIC DISC w/ BLURRED MARGINS

Miosis

Constriction, PARASYMPATHETIC
1. 1st neuron = Edinger-Westphal nucleus to ciliary ganglion via CN III
2. 2nd neuron = Short ciliary nerves to pupillary sphincter muscles

Pupillary Light Reflex

Light in either retina sends a signal via CN II to pretectal nuclei in MIDBRAIN that activates bilateral EDINGER-WESTPHAL NUCLEI
Pupils constrict bilaterally [Consensual reflex]

Resul: Illumination in one eye → Bilateral pupillary constriction

Mydriasis

DILATION, SYMPATHETIC
1st neuron: Hypothalamus to ciliospinal center of Budge [C8-T2]
2nd neuron: Exit at T1 to superior cervical ganglion [Travels along the cervical sympathetic chain near lung apex, subclavian vessels]
3rd neuron = Plexus along internal carotid, through cavernous sinus, enter orbit as LONG CILIARY NERVE to pupillary dilator muscles

SYMPATHETIC fibers also innervate SMOOTH MUSCLE OF EYELID [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 the eye relative to unaffected
Test w/ SWINGING FLASHLIGHT TEST

Horner Syndrome

SYMPATHETIC DENERVATION OF FACE
1. Ptosis [Slight drooping of eyelid = Superior tarsal muscle]
2. Anhidrosis [Absence of sweating] and flushing [Rubor] of affected side of face
3. Miosis [Pupil constriction]

Associated w/ lesion of spinal cord ABOVE T1
1. Pancoast tumor
2. Brown-Sequard syndrome [Cord hemisection]
3. Late stage syringomyelia

ANY INTERRUPTION RESULTS IN HORNERS
PAM is Horny

CN VI

Lateral Rectus

CN IV

Superior oblique
LR6SO4
Abducts, intorts, and depresses while abducted

CN III

Innervates all eye muscles except [LR, SO]

Obliques

go OPPOSITE [Left SO and IO tested with patients looking to the right]
IOU: IO tested looking up

CN III Damage

CN III has both motor [Central] and parasympathetic [Peripheral] components
Motor output to ocular muscles = Affected primarily by VASCULAR DISEASE [Diabetes mellitus: Glucose → Sorbitol]
-- Due to ↓ diffusion of oxygen and nutrients to interior fibers from compromised vasculature that resides on outside of nerves

DOWN AND OUT

Parasympathetic output = Fibers on periphery are 1st affected by compression [PICA aneurysm, uncal herniation]
-- Diminished or absent pupillary reflex
-- Blown pupil often w/ down and out gaze

CN IV Damage

Eyes move upward, particularly with CONTRALATERAL gaze
HEAD TILT TOWARD SIDE OF LESION
Problems going down stairs, may present w/ compensatory head tilt in opposite direction

CN VI Damage

MEDIALLY directed eye that cannot abduct

Visual Field Defects: Bitemporal hemianopsia

Pituitary lesion, chiasm

Visual Field Defects: Left upper quadrant anopia

Right temporal lesion, MCA

Visual Field Defects: Left lower quadrant anopia

Right parietal lesion, MCA

Visual Field Defects: Left hemianopia w/ macular sparing

PCA infarct

Visual Field Defects: Central scotoma

Macular degeneration

Meyer Loop

Inferior retina, loops around inferior horn of lateral ventricle

Dorsal Optic Radiation

Superior retina, takes SHORTEST PATH via INTERNAL CAPSULE

When an image hits the 1° Visual cortex, it is

Upside down, left-right reversed

Internuclear Ophthalmoplegia

Medial longitudinal fasciculus [MLF] = Pair of tracts that allow for crosstalk between CN VI and CN III nuclei
Coordinates both eyes to move in the same horizontal direction
HIGHLY MYELINATED [Must communicated quickly to move at the same time]
Lesions may be unilateral or bilateral [Seen in MS]

Lesion in MLF

Internuclear ophthalmoplegia [INO] results in conjugate horizontal gaze palsy
Lack of communication does not stimulate CN III to stimulate medial rectus to fire when CN VI nucleus activates
Abducting eye gets NYSTAGMUS [CN VI overfires to stimulate CN III]
CONVERGENCE NORMAL

Direction term [right INO, left INO] refers to which eye is paralyzed

Alzheimer Disease

Most common cause of DEMENTIA in elderly
DOWN SYNDROME patients have ↑ risk of developing Alzheimer's [Typically before age 40]
Familial Form [10%] associated with:
1. ApoE2 ↓ risk
2. ApoE4 ↑ risk
3. APP, presenilin-1, presenilin-2, = ↑ Risk of early onset
WIDESPREAD CORTICAL ATROPHY
-- Narrowing of gyri, widening of sulci
-- ↓ ACh

SENILE PLAQUES IN GRAY MATTER = Extracellular B-amyloid core [May cause amyloid angiopathy → intracranial hemorrhage]
AB [Amyloid B] synthesized by cleaving amyloid precursor APP

NEUROFIBRILLARY TANGLE = Intracellular, hyperphosphorylated tau protein
INSOLUBLE cytoskeletal elements

NUMBER OF TANGLES CORRELATED w/ DEGREE OF DEMENTIA

Dementia

A ↓ in cognitive ability, memory, or function with intact conciousness

Frontotemporal Dementia [Pick Disease]

Clinical Manifestations:
1. Dementia
2. Aphasia
3. Parkinsonian effects
4. Change in personality
SPARES PARIETAL LOBE and POSTERIOR 2/3 of superior temporal gyrus
PICK BODIES = Silver staining spherical tau protein aggregates

Lewy Body Dementia

Initially dementia and hallucinations [haLEWYcinations] followed by parkinsonian features
a-synuclein defect [Lewy bodies primarily cortical]

Creutzfeldt Jakob Disease

Rapidly progressive [Weeks to months] dementia with MYOCLONUS
Spongiform cortex [Associated w/ prions]
Prions [PrPc → PrPsc] B-pleated sheet are resistant to proteases

Multi-infarct Dementia [Vascular dementia]

2nd most common cause of DEMENTIA IN ELDERLY

Other Causes of Dementia

1. Syphilis
2. HIV [Associated w/ foamy macrophages and multinucleated giant cells, prominent endothelial cells]
3. Vitamins B1, B3, or B12 deficiency
4. Wilson disease
5. Normal pressure hydrocephalus [Wet, Wacky, Wobbly]

Multiple Sclerosis

AUTOIMMUNE INFLAMMATION and DEMYELINATION of CNS [Brain and spinal cord]
Patients can present with:
1. Optic neuritis [Sudden loss of vision resulting in Marcus Gun pupil]
2. INO
3. Hemiparesis
4. Hemisensory symptoms
5. BLADDER AND BOWEL INCONTINENCE
Relapsing and remitting course
Most often affects women in their 20-30s

Charcot Classic Triad [SIN]:
1. Scanning speech
2. Intention tremor [Also Incontinence and INO]
3. Nystagmus

Findings in MS

1. ↑ Protein [IgG] in CSF
2. Oligoclonal bands are diagnostic
3. MRI is gold standard
4. PERIVENTRICULAR PLAQUES [Areas of oligodendrocyte loss and reactive gliosis] with destruction of axons
5. Multiple white matter lesions separated in time and space

Treatment

Slow progression of disease with DMARDs [B-interferon, natalizumab]
Treat acute flares w/ IV STEROID
Symptomatic treatment for Neurogenic bladder:
1. Catheterization
2. Muscarinic antagonists

SPASTICITY
1. Baclofen
2. GABAB receptor agonist

PAIN = OPIOIDS

Acute Inflammatory Demyelinating Polyradiculopathy

Common common subtype of GUILLIAN BARRE
Autoimmune condition that destroys SCHWANN CELLS → Inflammation and demyelination of peripheral nerves and motor fibers
SYMMETRIC ASCENDING muscle weakness/paralysis beginning in lower extremities
FACIAL paralysis [50% of cases]
May see autonomic dysregulation:
1. Cardiac irregularities
2. Hypertension or hypotension
3. Sensory abnormalities

Almost all patients survive, majority recover completely after weeks to months

Findings:
1. ↑ CSF protein with NORMAL CELL COUNT [Albuminocytologic dissociation]
2. ↑ Protein may cause papilledema

Associated with:
1. Campylobacter jejuni infection [Autoimmune attack of peripheral myelin due to MOLECULAR MIMICRY and STRESS]

RESPIRATORY SUPPORT IS CRITICAL UNTIL RECOVERY
Treatment:
1. Plasmapheresis
2. IV Immunoglobulins

Acute Disseminated [Postinfectious] Encephalomyelitis

Multifocal PERIVENTRICULAR inflammation and demyelination after infection [Measles, VZV] or vaccinations [Rabies, smallpox]

Charcot-Marie-Tooth

Hereditary Motor and Sensory Neuropathy [HMSN]
Group of progressive disorders related to:
1. Defective production of proteins involved in structure and function of peripheral nerves or the myelin sheath
AUTOSOMAL DOMINANT
Associated with:
1. Scoliosis
2. Foot deformities [High or flat arches]

Krabbe Disease

AUTOSOMAL RECESSIVE LYSOSOMAL STORAGE DISEASE
Due to deficiency of GALACTOCEREBROSIDASE
Buildup of galactocerebroside and psychosine destroys myelin
Findings:
1. Peripheral neuropathy
2. Developmental delay
3. Optic atrophy
4. GLOBOID CELLS

Metachromatic Leukodystrophy

AUTOSOMAL RECESSIVE LYSOSOMAL STORAGE DISEASE
Most commonly due to ARYLSULFATASE A deficiency
Buildup of sulfatides → Impaired production and destruction of myelin sheath
Findings:
1. Central and peripheral demyelination
2. Ataxia
3. Dementia

Progressive Multifocal Leukoencephalopathy

Demyelination of CNS due to DESTRUCTION OF OLIGODENDROCYTES
Associated w/ JC virus
Seen in 2-4% of AIDS patients [Reactivation of latent virus]
Rapidly progressive, usually fatal
↑ Risk associated w/ Natalizumab, Rituximab

Adrenoleukodystrophy

X-LINKED genetic disorder
Typically affecting MALES
Disrupts metabolism of VERY LONG CHAIN FATTY ACIDS →
1. Excessive build-up in CNS, adrenal glands, testes
2. Progressive disease that can lead to long-term coma/death
3. ADRENAL GLAND CRISIS

Seizures

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

Partial [Focal] Seizure

AFFECTS SINGLE AREA OF BRAIN
Most commonly in MEDIAL TEMPORAL LOBE
Often preceded by seizure AURA, can secondarily generalize

Simple Partial Seizure

Consciousness intact
Motor, sensory, autonomic, psychic

Complex Partial Seizure

Impaired Consciousness

Generalized Absence Seizure [Petit mal]

3 Hz, NO POSTICTAL confusion, blank stare

Generalized Myoclonic Seizure

Quick, repetitive jerks

Generalized Tonic-Clonic Seizure [Grand Mal]

Alternating stiffening and movement

Generalized Tonic Seizure

Stiffening

Generalized Atonic Seizures

Drop seizures [Falls to floor], commonly mistaken for fainting
Typically starts in childhood [6 months - 5 years]

Epilepsy

Disorder of recurrent seizures [Febrile seizures are not epilepsy]

Status epilepticus

Continuous or recurring seizures that may result in brain injury
Variably defined as > 10-30 minutes

Causes of Seizure by Age
1. Children
2. Adults
3. Elderly

CHILDREN
1. Genetic
2. Infection [Febrile]
3. Trauma
4. Congenital
5. Metabolic

ADULTS
1. Tumor
2. Trauma
3. Stroke
4. Infarction

ELDERLY
1. Stroke
2. Tumor
3. Trauma
4. Metabolic
5. Infection

Cluster Headache

Unilateral
Duration: 15 min- 3 hours, repetitive
REPETITIVE BRIEF HEADACHES
Excruciating, PERIORBITAL pain w/ LACRIMATION and RHINORRHEA
May induce horner's syndrome
More common in MALES
Treatment: 100% O2

Tension Headache

BILATERAL
Duration: > 30 minutes [Typically 4-6 hours], Constant
STEADY PAIN
Treatment: Analgesics, NSAIDs, Acetaminophen, Amitriptyline for chronic pain

Migraine

Unilateral
Duration: 4-72 hours
Clinical Manifestation [POUND]
1. Pounding/Pulsatile
2. One-day duration
3. Unilateral
4. Nausea and vomiting
5. Disabling
6. PHOTOPHOBIA or PHONOPHOBIA
7. May have aura

Due to irritation of CN V, meninges, blood vessels [Release of substance P, calcitonin gene-related peptide, vasoactive peptide]

Treatment:
1. Abortive therapies [Triptans, NSAIDs]
2. Prophylaxis [Propranolol, Topiramate, Ca2+ channel blockers]

Other causes of headaches:

1. Subarachnoid Hemorrhage
2. Meningitis
3. Hydrocephalus
4. Neoplasia
5. Arteritis

Trigeminal Neuralgia

REPETITIVE SHOOTING PAIN in the distribution of CN V
Typically lasts for < 1 minute

Vertigo

Sensation of spinning while actually stationary
Subtype of dizziness, but distinct from light-headedness

Peripheral vertigo

MORE COMMON
INNER EAR ETIOLOGY
1. Semicircular debris
2. Vestibular nerve infection
3. Meniere Disease

Positional testing → DELAYED HORIZONTAL NYSTAGMUS

Central vertigo

BRAIN STEM or CEREBELLAR lesion
STROKE affecting VESTIBULAR or POSTERIOR FOSSA TUMOR
Findings:
1. Direction change of nystagmus
2. Skew deviation
3. Diplopia
4. Dysmetria
Positional testing → Immediate nystagmus in any direction, may change directions
FOCAL NEUROLOGIC FINDINGS

Sturge-Weber Syndrome

Congenital, non-inherited [Somatic] developmental anomaly of NEURAL CREST DERIVATIVES [Mesoderm/Ectoderm]
1. Due to activating mutation of GNAQ
2. Affects small [Capillary-sized] blood vessels → Port wine stain of face
2. Nevus flammeus = Non-neoplastic birthmark in CN V1/V2 distribution
3. Ipsilateral leptomeningeal angioma
4. Seizures/epilepsy
5. Intellectual disability
6. Episcleral hemangioma
7. ↑ IOP → Early onset GLAUCOMA

STURGE-Weber
1. Sporadic, port-wine stain
2. Tram track calcifications
3. Unilateral
4. Retardation [Intellectual disability]
5. Glaucoma, GNAQ
6. Epilepsy

Tuberous Sclerosis

HAMARTOMAS
1. Hamartomas in CNS
2. Angiofibromas
3. MITRAL REGURGITATION
4. Ash-leaf spots
5. Cardiac RHABDOMYOMA
6. Autosomal dOminant
7. Mental retardation [Intellectual disability]
8. Renal Angiomyolipoma
9. Seizures, Shagreen patches

↑ Incidence in subependymal astrocytomas and ungual fibromas

Neurofibromatosis Type I [Von Recklinghausen Disease]

1. Cafe-au-lait spots
2. Lisch nodules [Pigmented iris hamartomas]
3. Cutaneous neurofibromas
4. Optic gliomas
5. Pheochromocytomas

Mutated NF1 TUMOR SUPPRESSOR GENE [Neurofibromin = Negative regulator of RAS] on chromosome 17

Skin tumors of NF-1 are derived from neural crest cells

von Hippel-Lindau Disease

X-Linked Recessive
HEMANGIOBLASTOMAS [High vascularity w/ HYPERCHROMATIC NUCLEI] in:
1. Retina
2. Brainstem
3. Cerebellum
4. Spine
Angiomatosis = Cavernous hemangiomas in skin, mucosa, organs
BILATERAL RENAL CELL CARCINOMAS
Pheochromocytomas

Glioblastoma Multiforme [Grade IV Astrocytoma]

Common, HIGHLY MALIGNANT 1° brain tumor with ~ 1 year survival
Found in CEREBRAL HEMISPHERES
CAN CROSS CORPUS CALLOSUM [Butterfly glioma]
Stain astrocytes for GFAP
Histology:
1. Pseudopalisading
2. Pleomorphic tumor cells
3. Border CENTRAL AREAS OF NECROSIS and hemorrhage

Meningioma

Common, typically BENIGN 1° brain tumor
Most often occurs in CONVEXITIES of hemispheres near surfaces of the brain and PARASAGITTAL SINUS
Arises from ARACHNOID CELLs
EXTRA-AXIAL [External to brain parenchyma]
May have a DURAL ATTACHMENT [Tail]
Often asymptomatic, may present w/:
1. Seizures
2. Focal neurologic signs

Treatment = Resection or radiosurgery
Histology:
1. SPINDLE cells concentrically arranged in WHORLED PATTERN
2. PSAMMOMA BODIES [Laminated calcifications]

Hemangioblastoma

Most often CEREBELLAR
Associated w/ von-Hippel-Lindau syndrome
Found with RETINAL ANGIOMAS
Can produce ERYTHROPOIETIN → 2° Polycythemia
Histology:
1. Closely arranged, thin-walled capillaries with minimally intervening parenchyma

Schwannoma

Classically at CEREBELLOPONTINE ANGLE, but can be anywhere along peripheral nerve
Schwann cell origin [S-100]
Often LOCALIZED TO CN VIII → Vestibular schwannoma
Resectable or treatable w/ stereotactic radiosurgery
BILATERAL VESTIBULAR SCHWANNOMA = NF2

Oligodendroglioma

Relatively rare, slow growing
Most often in FRONTAL LOBES
CHICKEN-WIRE capillary pattern
Histology:
1. Oligodendrocytes = FRIED EGG cells [Round nuclei with clear cytoplasm]
OFTEN CALCIFIED

Pituitary Adenoma

Most commonly prolactinoma
Bitemporal hemianopia [Normal visual fields above] due to pressure on the Optic Chiasm

Pilocytic [Low-Grade] Astrocytoma

Usually well-circumscribed
In CHILDREN
Found in the POSTERIOR FOSSA [Cerebellum]
May be supratentorial
GFAP +
Benign, good prognosis
ROSENTHAL FIBERS = Eosinophilic, corkscrew fibers
CYSTIC + SOLID

Medulloblastoma

HIGHLY MALIGNANT CEREBELLAR tumor
A form of primitive NEUROECTODERM
Can compress 4th ventricle causing hydrocephalus
Can send DROP METASTASES to spinal cord

HOMER-WRIGHT ROSETTE
Solid, SMALL BLUE CELLS

Ependymoma

Ependymal cells most commonly found in the 4th ventricle
Can cause hydrocephalus
POOR PROGNOSIS
Characteristic perivascular rosettes
Rod-Shaped Blepharoplasts [Basal ciliary bodies] found near nucleus

Craniopharyngioma

Benign CHILDHOOD tumor
Can cause bitemporal hemianopia
MOST COMMON CHILDHOOD SUPRATENTORIAL tumor
Derived from remnants of Rathke's pouch
Calcification common

Cingulate [Subfalcine] Herniation under Falx Cerebri

Can compress anterior cerebral artery

Downward Transtentorial [Central] Herniation

Caudal displacement of brain stem → Rupture of PARAMEDIAN BASILAR ARTERY BRANCHES → Duret's hemorrahges

Uncal Herniation

Uncus = Medial Temporal lobe
1. Compresses Ipsilateral CN III [Blown pupil, down and out]
2. Ipsilateral PCA [Contralateral homonymous hemianopia]
3. Contralateral Crus cerebri at the Kernohan notch [Ipsilateral paresis = False localization sign]

Cerebellar Tonsillar Herniation into the Foramen Magnum

Coma and death result when the herniations compress the brain stem

Glaucoma Drugs

↓ IOP via ↓ Amount of aqueous humor [Inhibits synthesis/secretion of ↑ drainage]

a-agonists

Drugs: Epinephrine [a1], Brimonidine [a2]
MOA:
1. ↓ Aqueous humor synthesis via vasoconstriction
2. ↓ Aqueous humor synthesis

Side Effects:
1. Mydriasis [a1] = Do not use in CLOSED-ANGLE glaucoma
2. Blurry vision
3. Ocular hyperemia
4. Foreign body sensation
5. Ocular allergic rxns
6. Ocular pruritus

B-blockers

Timolol, Betaxolol, Carteolol
MOA: ↓ Aqueous humor synthesis

Acetazolamide

MOA: ↓ Aqueous humor synthesis via inhibition of carbonic anhydrase

Direct Cholinomimetics [Pilocarpine, Carbachol]
Indirect Cholinomimetics [Physostigmine, Echothiophate]

MOA: ↑ Outflow of aqueous humor via CONTRACTION OF CILIARY MUSCLE and OPENING OF TRABECULAR NETWORK

Use pilocarpine in emergencies = Very effective at opening meshwork into canal of Schlemm

Adverse Effects:
Miosis and cytoplasm [Contraction of ciliary muscle]

Latanoprost [PGF2a]

↑ Outflow of aqueous humor

Adverse Effect:
Darkens color of iris [Browning]

Opioid Analgesics

Drugs: Morphine, Fentanyl, Codeine, Loperamide, Methadone, Meperidine, Dextromethorphan, Diphenoxylate, Pentazocine

MOA: Acts as agonists at opioid receptors [μ = Morphine, δ = Enkephalin, ⱪ = dynorphin] to modulate synaptic transmission
Opens K+ channels, closes Ca2+ channels → ↓ Synaptic transmission
Inhibits release of
1. ACh
2. Norepinephrine
3. 5-HT
4. Glutamate
5. Substance P

Clinical Use of Opioids

1. Pain
2. Cough suppression [Dextromethorphan]
3. Diarrhea [Loperamide, diphenoxylate]
4. Acute pulmonary edema
5. Maintenance programs for heroin addicts [Methadone, buprenorphine + Naloxone]

Toxicity of Opioids

1. Addiction
2. Respiratory depression
3. Constipation
4. Miosis [Pinpoint pupils]
5. Addictive
6. CNS depression w/ other drugs
TOLERANCE DOES NOT DEVELOP TO MIOSIS AND CONSTIPATION
Toxicity treated w/ Naloxone or Naltrexone [Opioid receptor antagonist]

Butorphanol

MOA: ⱪ-opioid receptor agonist and μ partial agonist
Produces analgesia

Clinical Use:
1. Severe pain [Migraine, labor]
2. Causes less respiratory depression than full opioid agonists

Adverse Effects:
1. Can cause opioid withdrawal symptoms if a patient is also taking full opioid agonist [Competition for opioid receptors]
2. Overdose not easily reversed with naloxone

Tramadol

MOA: Very weak opioid agonist
Also inhibits 5-HT and Norepi REUPTAKE [Works on multiple neurotransmitters -Tram it all w/ TRAMADOL]
Clinical Use:
1. Chronic pain
Toxicity:
1. Similar to opioid
2. DECREASES SEIZURE THRESHOLD
3. SEROTONIN SYNDROME

Ethosuximide [Epilepsy]

ABSENCE SEIZURES
MOA: Blocks thalamic T-Type Ca2+ Channels

Side Effects [EFGHIJ]:
1. Fatigue
2. GI upset
3. Headache
4. Itching
5. SJS

Benzodiazepines [Epilepsy]

FIRST LINE TREATMENT IN STATUS EPILEPTICUS
1. Diazepam, Lorazepam, Clonazepam
MOA: ↑ GABAA action

Side effects
1. Sedation
2. Tolerance
3. Dependence
4. Respiratory depression and hypotension

Phenytoin, Fosphenytoin [Parenteral]

MOA: ↑ Na channel inactivation, zero order kinetics

Side Effects:
1. Nystagmus, diplopia
2. Ataxia
3. Sedation
4. GINGIVAL HYPERPLASIA
5. Hirsutism
6. Peripheral neuropathy
5. MEGALOBLASTIC ANEMIA
6. Teratogenic [Fetal hydantoin syndrome]
7. SJS
8. Osteopenia

Carbamazepine [Epileptic]

1st LINE FOR TRIGEMINAL NEURALGIA
MOA: ↑ Na channel inactivation, potentiates K+ efflux

Side Effects:
1. Diplopia
2. Ataxia
3. Blood dyscrasias [AGRANULOCYTOSIS, APLASTIC ANEMIA]
4. Liver toxicity
5. SIADH
7. SJS
8. Osteopenia

Valproic acid [Epileptic]

USED FOR MYOCLONIC SEIZURES, BIPOLAR DISORDER
MOA: ↑ Na channel inactivation, ↑ GABA concentration by inhibiting GABA transaminase

Side Effects:
1. FATAL hepatotoxicity [Check LFTs]
2. Neural tube defects [Spina bifida]
3. Tremor
4. Weight gain
5. Contraindicated in pregnancy

Gabapentin [Epileptic]

MOA: Primarily inhibits high-voltage-activated Ca2+ channels, designed as GABA analog

Side Effects:
1. Sedation
2. Ataxia

Phenobarbital [Epileptic]

FIRST LINE IN NEONATES
MOA: ↑ GABAA action

Side Effects:
1. Sedation
2. Tolerance
3. Dependence
4. Cardiorespiratory depression

Topiramate [Epileptic]

Also used for migraine prevention
MOA: Blocks Na channels, ↑ GABA action

Side Effects:
1. Sedation
2. Mental dulling
3. Kidney stones
4. Weight loss

Lamotrigine [Epileptic]

MOA: Blocks voltage-gated Na channels, blocks glutamate release

Side Effects:
1. SJS

Levetiracetam [Epileptic]

MOA: Unknown, may modulate GABA and glutamate release

Tiagabine [Epileptic]

MOA: ↑ GABA by inhibiting reuptake

Vigabatrin [Epileptic]

MOA: ↑ GABA by irreversibly inhibiting GABA Transaminase

SJS

Prodrome of fever, malaise followed by rapid onset of erythematous/pruritic macules [Oral, ocular, genital]. Skin lesions progress to epidermal necrosis and sloughing

Barbiturates

Drugs: Phenobarbital, Pentobarbital, Thiopental, Secobarbital
MOA: Facilitate GABAA action by ↑ DURATION of Cl- channel opening → ↓ Neuron firing
CONTRAINDICATED IN PORPHYRIA

Clinical Use:
1. Sedative for anxiety
2. Seizures
3. Insomnia
4. Induction of anesthesia [Thiopental]

Adverse Effects:
1. Respiratory and cardiovascular depression [Can be fatal]
2. CNS depression [Can be exacerbated by EtOH use]
3. Dependence
4. Drug interactions [Induces CYP450]

Treatment of OD = Supportive [Assist respirations, maintain BP]

Benzodiazepines

Drugs: Diazepam, lorazepam [Anticonvulsants], Triazolam [Insomnia], Temazepam, Oxazepam, Midazolam, Chlordiazepoxide, Alprazolam

MOA: Facilitate GABAA action by ↑ FREQUENCY of Cl- channel opening
↓ REM sleep
Most have long half-lives and active metabolites, exceptions [ATOM = High addictive potential]:
1. Alprazolam
2. Triazolam
3. Oxazepam
4. Midazolam

What binds GABAA

Benzos, Barbs, EtOH

Clinical Use of Benzodiazepines

1. Anxiety
2. Spasticity
3. Status epilepticus [Diazepam, Lorazepam]
4. Detoxification [Especially alcohol withdrawal]
5. Night terrors, sleepwalking
6. General anesthetic [Amnesia, muscle relaxant]
7. Hypnotic [Insomnia]

Benzodiazepine Toxicity

1. Dependence
2. Addictive CNS depression effects w/ alcohol
3. Less risk of respiratory depression and coma than with barbiturates
Treat overdose with: Flumazenil [Competitive antagonist at GABA benzodiazepine receptor]

Nonbenzodiazepine Hypnotics

Drugs: Zolpidem, Zaleplon, eZopiclone [All ZZZs put you to sleep]
MOA: Act via the BZI subtype of GABA receptor
Effects reversed by Flumazenil

Clinical use:
1. Insomnia

Adverse Effects:
1. Ataxia
2. Headaches
3. Confusion
Short duration because of rapid metabolism by liver enzymes. Unlike older sedative-hypnotics, cause only modest day-after psychomotor depression and a few amnestic effects
↓ Dependence risk compared to benzos

Anesthetics - General Principles

1. CNS drugs must be lipid soluble [Cross the BBB] or be actively transported
2. Drugs w/ ↓ solubility in blood = Rapid induction and recovery time
3. Drugs w/ ↑ solubility in lipid = ↑ Potency = 1/MAC

Minimal Alveolar Concentration [MAC]

Inhaled anesthetic = Required to prevent 50% of subjects from moving in response to noxious stimulant [skin incision]
Examples: Nitric oxide [N2O] has ↓ solubility in blood and ↓ lipid solubility = Fast induction and low potency
Halothane = ↑ Lipid and blood solubility, high potency and slow induction

Inhaled anesthetics

Drugs: Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, N2O

Effects:
1. Myocardial depression
2. Respiratory depression
3. Nausea/emesis
4. ↑ Cerebral blood flow [↓ Cerebral metabolic demand]

Adverse Effects:
1. Hepatotoxicity [Halothane]
2. Nephrotoxicity [Methoxyflurane]
3. Proconvulsant [Enflurane]
34. Expansion of trapped gas in the body [N2O]

Malignant Hyperthermia

Rare. life-threatening hereditary condition in which inhaled anesthetics [N2O] and succinylcholine induce FEVER and SEVERE MUSCLE CONTRACTIONS

Treatment = Dantrolene

Intravenous Anesthetics: Barbiturates

Thiopental
HIGH POTENCY, HIGH SOLUBILITY
Rapid re-entry into brain
Used for induction of anesthesia and short surgical procedures
Effect terminated by rapid redistribution into tissue [skeletal muscle] and fat
↓ Cerebral flow

Intravenous Anesthetics: Benzodiazepines

Midazolam most commonly used for ENDOSCOPY
Used adjunctively with gaseous anesthetics and narcotics
May cause SEVERE POST-OPERATIVE RESPIRATORY DEPRESSION
ANTEROGRADE AMNESIA
↓ BlP
Treat OD: Flumazenil

Arylcyclohexylamines [Ketamine]

PCP analogs that act as dissociated anesthetics
Block NMDA receptors
CARDIOVASCULAR STIMULANTS
Cause:
1. Disorientation
2. Hallucination
3. Bad dream
4. ↑ Cerebral blood flow

Opioids

Morphine, fentanyl
Used with other CNS depressants during general anesthesia

Propofol

Used for sedation in the ICU, rapid anesthesia induction, short procedures
LESS POST-OPERATIVE NAUSEA than thiopental
Potentiates GABAA

Local Anesthetics

Esters = Procaine, cocaine, tetracaine
Amides = Lidocaine, Mepivacaine, Bupivacaine [Amides have two I's]

MOA: Binds Na+ channels by binding to specific receptor on inner portion of channel
Preferentially binds to ACTIVATED NA+ CHANNELS [Most effective in firing neurons]
3° amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form

Principle of Local Anesthetics

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 for Local Anesthetics

Small-diameter > Large Diameter
Myelinated fibers > Unmyelinated fibers
SIZE 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

Toxicity of Local Anesthetics

1. CNS excitation
2. Severe cardiovascular toxicity [Bupivacaine]
3. Hypertension/Hypotension
4. Arrhythmias [Cocaine]
5. Methemoglobinemia [Benzocaine]

Neuromuscular Blocking Drugs

Muscle paralysis in surgery or mechanical ventilation
Selective for motor [vs. autonomic] nicotinic receptors

Depolarizing Neuromuscular Blocking Agents

Drug: Succinylcholine
MOA: Strong ACh receptor agonist, produces SUSTAINED DEPOLARIZATION and PREVENTS MUSCLE CONTRACTION
Reversal of Blockade:
1. Phase I [Prolonge depolarization] = No antidote
-- Block potentiated by cholinesterase inhibitors
2. Phase II [Repolarized but blocked] = ACh receptors are available but desensitized
Antidote = Cholinesterase Inhibitors

Complications:
1. Hypercalcemia
2. Hyperkalemia
3. Malignant hyperthermia

Nondepolarizing Neuromuscular Blocking Agents

Drugs: Tubocurarine, Atracurium, Mivacurium, Pancuronium, Vecuronium, Rocuronium
MOA: Competitive antagonist, compete w/ ACh receptors

Reversal of blockade:
1. NEOSTIGMINE [Must be given with atropine to prevent muscarinic effects = Bradycardia]
2. Edrophonium
3. Other cholinesterase inhibitors

Dantrolene

MOA: Prevents release of Ca2+ from sarcoplasmic reticulum of skeletal muscle
Clinical Use:
1. Malignant hyperthermia
2. Neuroleptic malignant syndrome [Toxicity of antipsychotic drugs]

Baclofen

MOA: Inhibits GABAB receptors at spinal cord, inducing skeletal muscle relaxation
Clinical Use: Muscle spasms

Cyclobenzaprine

MOA: Centrally acting skeletal muscle relaxant
Structurally related to TCAs
Similar anticholinergic side effects
Clinical Use: Muscle spasms

Dopamine Agonists

Ergot = Bromocriptine
Non-ergot [Preferred] = Pramipexole, Ropinirole

↑ Dopamine Availability

Amantadine
↑ Dopamine release and ↓ Dopamine Reuptake
Also used as an antiviral against influenza A and rubella

Toxicity
1. Ataxia
2. 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 block peripheral conversion of L-Dopa to dopamine by inhibiting DOPA decarboxylase
Also reduces side effects of peripheral L-dopa conversion into dopamine [Nausea and Vomiting]
Entacapone, Tolcapone = Prevent peripheral L-dopa degradation to 3-O-methyldopa [3-OMD] by inhibiting COMT

Prevent dopamine breakdown

Agents act centrally [post-BBB] to block break down of dopamine → ↑ Available Dopamine
1. Selegiline = Blocks conversion of dopamine into 3-MT by selectively inhibiting MOA-B
2. Tolcapone = Blocks conversion of dopamine by DOPAC by inhibiting central COMT

Curb Excess Cholinergic Activity

Benztropine [Antimuscarinic, improves TREMOR and RIGIDITY, but has little effect on BRADYKINESIA]

L-Dopa

Drug: Levodopa/Carbidopa
MOA: ↑ LEvel of dopamine in the brain
Unlike dopamine, L-dopa can cross the BBB and is converted by dopa decarboxylase in the CNS to dopamine
Carbidopa [Peripheral dopa decarboxylase inhibitor] is given with L-dopa to ↑ the bioavailability of L-dopa in the brain and limit peripheral side effects

Clinical Use: Parkinson's 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

Selectively inhibits MOA-B, which preferentially metabolizes dopamine over norepinephrine and 5-HT, ↑ availability of dopamine

Clinical Use: Adjunctive agent to L-dopa in treatment of PArkinson Disease

Toxicity: May enhance adverse effects of L-dopa

Alzheimer drugs [Memantine]

Drug: Memantine
MOA: NMDA receptor antagonist, helps prevent excitotoxicity [Mediated by Ca2+]
Toxicity: Dizziness, confusion, hallucination

Alzheimer drugs [Donepezil, Galantamine, Rivastigmine, Tacrine]

MOA: AChE inhibitors
Toxicity: Nausea, dizziness, insomnia

Huntington Disease Drugs

Neurotransmitter changes in Huntington Disease [↓ GABA, ↓ ACh, ↑ Dopamine]
Treatments:
1. Tetrabenazine and Reserpine = Inhibit vesicular monoamine transporter [VMAT]
-- Limits DOPAMINE VESICLE PACKAGE AND RELEASE
2. Haloperidol = D2 receptor antagonist

Triptans

Sumatriptan
MOA: 5-HT 1B/1D agonist
-- INHIBITS TRIGEMINAL NERVE ACTIVATION
-- Prevents vasoactive peptide release
-- Induces vasoconstriction
Clinical Use: Acute migraine, cluster headache attacks
Adverse Effects:
1. Coronary vasospasm [Contraindicated in patients w/ CAD or Prinzmetal angina]
Mild paresthesia

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