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USMLE Step 1. > Neuro > Flashcards

Flashcards in Neuro Deck (209):
1

Cinchonism (drug reaction)

Quinidine
Quinine

2

Parkinson-like Syndrome (drug reaction)

Antipsychotics
Reserpine
Metoclopramide

3

Seizures (drug reaction)

Isoniazid (B6 deficiency)
Bupropion
Imipenem/cilastatin
Enflurane

4

Tardive dyskinesia (drug reaction)

Antipsychotics
Metoclopramide

5

Neural development

Notochord induces overlying ectoderm to differentiate into neuroectoderm and form neural plate

Neural plate gives rise to neural tube and neural crest cells

Notochord becomes nucleus pulposus of IV discs in adults

Alar plate (dorsal) = sensory (same as SC)

Basal plate (ventral) = motor (same as SC)

6

Regional specification of developing brain

1) Forebrain (prosencephalon)
- Branches into Telencephalon - Cerebral hemispheres and lateral ventricles

- Also into Diencephalon - Thalamus and 3rd ventricle

2) Midbrain (mesencephalon) - Midbrain and Aqueduct

3) Hindbrain - Metencephalon and Myelencephalon
- Metencephalon - Pons, Cerebellum, Upper part of 4th ventricle

- Myelencephalon - Medulla and lower part of 4th ventricle

7

CNS/PNS origins

Neuroectoderm - CNS, neurons, ependymal cells (inner lining of ventricles, make CSF), oligodendroglia, astrocytes

Neural crest - PNS neurons, Schwann cells

Mesoderm - Microglia (like Macrophages)

8

Neural tube defects

Neuropores fail to fuse (4th week) causing persistent connection between amniotic cavity and spinal canal

Associated with low folic acid intake before conception and during pregnancy.

Increased alpha-fetoprotein (AFP) in amniotic fluid and maternal serum

Increased acetylcholinesterase (AChE) in amniotic fluid is a helpful confirmatory test (fetal AChE in CSF transudates across defect into amniotic fluid)

9

Spina bifida occulta

Failure of bony spinal canal to close, but no structural herniation.

Usually seen at lower vertebral levels. Dura is intact. Associated with tuft of hair or skin dimple at level of bony defect. Normal AFP

10

Menigocele

Meninges (but no neural tissue) herniate through bony defect

11

Meningomyelocele

Meninges and neural tissue herniate through bony defect

12

Anencephaly

Forebrain anomaly

Malformation of anterior neural tube leads to no forebrain, open calvarium.

Clinical findings: High AFP; polyhydramnios (no swallowing center in brain)

Associated with maternal type 1 diabetes.

Maternal folate supplementation lowers risk

13

Holoprosencephaly

Forebrain anomaly

Failure of left and right hemispheres to separate; usually occurs during weeks 5-6

May be related to mutations in sonic hedgehog signaling pathway. Moderate form has cleft palate/lip, most severe form results in cyclopia.

Seen in Patau syndrome and Fetal Alcohol Syndrome

14

Chiari II

Posterior fossa malformation

Significant herniation of cerebellar tonsils and vermis through foramen magnum with aqueductal stenosis and hydrocephalus.

Often presents with lumbrosacral meningomyelocele, paralysis below the defet

15

Dandy-Walker

Posterior fossa malformation

Agenesis of cerebellar vermis with cystic enlargement of 4th ventricle (fills the enlarged posterior fossa)

Associated with hydrocephalus, spina bifida

16

Syringomyelia

Cystic cavity (syrinx) within spinal cord (if central canal - hydromyelia)

Crossing anterior spinal commissural fibers are typically damaged first. Results in a "cape-like" bilateral loss of pain and temperature sensation in upper extremities (fine touch sensation is preserved)

Associated with Chiari malformations, trauma, and tumors

Syrinx = tube, as in syringe

Most common at C8-T1

Chiari I malformation - cerebellar tonsillar ectopia > 3-5mm; congenital, usually asymptomatic in childhood, manifests with headaches and cerebellar symptoms

17

Tongue development

1st and 2nd branchial arches form anterior 2/3 (thus sensation via CN V3, taste via CN VII)

3rd and 4th branchial arches form posterior 1/3 (thus sensation and taste mainly via CN IX, extreme posterior via CN X)

Motor innervation is via CN XII to hypoglossus (retracts and depresses tongue), genioglossus (protrudes tongue), and styloglossus (draws sides of tongue upward to create a trough for swallowing)

Motor innervation is via CN X to palatoglossus (elevates posterior tongue during swallowing)

Taste - CN 7, 9, 10 (solitary nucleus)

Pain - CN V3, 9, 10

Motor - CN 10, 12

18

Neurons

Signal transmitting cells of the nervous system. Permanent cells - do not divide in adulthoos.

Signal-relaying cells with dendrites (receive input), cell bodies, and axons (send output)

Cell bodies and dendrites can be seen on Nissle Stain* (stains RER)

RER is not present in the axon.

Injury to axon leads to Wallerian degeneration - degeneration distal to injury and axonal retraction proximally; allows for potential regeneration of axon (if in PNS)

19

Astrocytes

Physical support, repair, K metabolism, removal of excess nt's, component of BBB, glycogen fuel reserve buffer. Reactive gliosis in response to neural injury.

Astrocyte marker = GFAP

Derived from neuroectoderm

20

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

21

Myelin

Increases conduction velocity of signals transmitted down axons - saltatory conduction of action potential at the nodes of Ranvier, where there are high concentrations of Na channels.

CNS - oligodendrocytes

PNS - Schwann Cells

Wraps and insulates axons: Increases space constant and Increases conduction velocity

22

Schwann cells

Each Schwann cell myelinates only 1 PNS axon

Also promote axonal regeneration. Derived from neural crest

Increased conduction velocity via saltatory conduction at the nodes of Ranvier, where there is a high concentration of Na channels

May be injured in Guillain-Barre Syndrome

Acoustic Neuroma - type of schwannoma. Typically located in internal acoustic meatus (CN8). If bilateral, strongly associated with neurofibromatosis type 2

23

Oligodendroglia

Myelinates axons of neurons in CNS. Each oligodendrocyte can myelinate many axons (~30). Predominant type of glial cell in white matter

Derived from neuroectoderm

"Fried egg" appearance histologically

Injured in MS, progressive multifocal leukoencephalopathy (PML), leukodystrophies

24

Free nerve endings

C - slow, unmyelinated fibers
Adelta - fast, myelinated fibers

Location: All skin, epidermis, some viscera

Senses: Pain and temp

25

Meissner corpuscles

Large, myelinated fibers; adapt quickly

Location: Glabrous (hairless) skin

Senses: Dynamic, fine/light touch, position sense

26

Pacinian corpuscles

Large, myelinated fibers; adapt quickly

Location: Deep skin layers, ligaments, joints

Senses: Vibration, pressure

27

Merkel discs

Large, myelinated fibers; adapt slowly

Location: Finger tips, superficial skin

Senses: Pressure, deep static touch (shapes, edges), position sense

28

Ruffini corpuscles

Dendritic endings with capsule; adapt slowly

Locations: Finger tips, joints

Senses: Pressure, slippage of objects along surface of skin, joint angle change

29

Peripheral nerve makeup

Endoneurium - invests single nerve fiber layers (inflammatory infiltrate in Guillain-Barre syndrome)

Perineurium (permability barrier) - surrounds a fascicle of nerve fibers. Must be rejoined in microsurgery for limb reattachment

Epineurium - dense connective tissue that surrounds entire nerve (fascicles and blood vessels)

30

Norepinephrine

Increased in anxiety
Decreased in depression

made in Locus Ceruleus (pons)

Locus ceruleus = stress and panic center

31

Dopamine

Increased in Huntington Disease
Decreased in Parkinson Disease
Decreased in Depression

Made in Ventral tegmentum and substantia nigra pars compacta (midbrain)

32

5-HT

Decreased in anxiety
Decreased in Depression

Made in Raphe nuclei (pons, medulla, midbrain)

33

ACh

Increased in Parkinson Disease
Decreased in Alzheimer Disease
Decreased in Huntington Disease

Made in Basal nucleus of Meynert

34

GABA

Decreased in anxiety
Decreased in Huntington Disease

Made in nucleus accumbens

Nucleus accumbens and septal nucleus - reward center, pleasure, addiction, fear

35

Blood Brain Barrier

Prevents circulating blood substances (bacteria, drugs) 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 substances cross rapidly via diffusion

A few specialized brain regions with fenestrated capillaries and no BBB allow molecules in blood to affect brain function (area postrema - vomiting after chemo; OVLT - osmotic sensing) or neurosecretory products to enter circulation (neurohypophysis - ADH release)

Infarction and/or neoplasm destroys endothelial cell tight junctions leading to vasogenic edema

Other notable barriers include:
Blood testis barrier
Maternal-fetal blood barrier of placenta

36

Hypothalamus

The hypothalamus wears TAN HATS

T = Thirst and water balance
A = adenohypophysis control (regulates anterior pit)
N = Neurohypophysis releases hormones produced in the hypothalamus
H = Hunger
A = Autonomic regulation
T = Temperature regulation
S = Sexual urges

Inputs (areas not protected by BBB): OVLT (Organum Vasculosum of the Lamina Terminalis; senses change in osmolarity), Area postrema (responds to emetics)

Supraoptic nucleus - makes ADH

Paraventricular nucleus - makes oxytocin

ADH and oxytocin - made by hypothalamus but stored and released by posterior pit.

37

Lateral area of hypothalamus

Hunger

Destruction leads to anorexia, failure to thrive (infants). Inhibited by leptin

"If you zap your lateran nucleus you shrink laterally"

38

Ventromedial area of hypothalamus

Satiety

Destruction (craniopharyngioma) leads to hyperphagia. Stimulated by leptin

"If you zap your ventromedial nucleus, you grow ventrally and medially"

39

Anterior hypothalamus

Cooling, parasympathetic

"Anterior/Cooling = A/C"

40

Posterior hypothalamus

Heating, sympathetic

41

Suprachiasmatic nucleus

Circadian Rhythm

"You need sleep to be charismatic"

42

Sleep physiology

Sleep cycle is regulated by the circadian rhythm, which is driven by suprachiasmatic nucleus (SCN) of hypothalamus

Circadian rhythm controls nocturnal release of ACTH, prolactin, melatonin, NE: SCN triggers NE release to the pineal gland which releases melatonin

SCN is regulated by environment (light)

2 stages: REM and non-REM. Extraocular movements during REM sleep due to activity of PPRP (Paramedian Pontine Reticular Formation/Conjugate Gaze Center)

REM sleep occurs every 90 minutes, and duration increases throughout the night

Alcohol, benzos and barbs are associated with reduced REM sleep and delta wave sleep; NE also reduces REM sleep

Treat bedwetting (sleep enuresis) with oral desmopressin (ADH analog); preferred over imipramine bc of the latter's adverse effects

Benzos are useful for night terrors and sleepwalking

43

Sleep stages

1) Awake (eyes open) - alert, active mental concentration
Beta (highest frequency, lowest amplitude) waves on EEG

2) Awake (eyes closed) - Alpha waves

3) Non-REM sleep
- Stage N1 (5%) - Light sleep - Theta waves
- Stage N2 (45%) - Deeper sleep; when bruxism occurs - sleep spindles and K complexes on EEG
- Stage N3 (25%) - Deepest non-REM sleep (slow wave sleep); When sleepwalking, night terros, and bedwetting occur - Delta waves (lowest frequency, highest amplitude)

4) REM sleep (25%) - Loss of motor tone, increased brain O2 use, increased and variable pulse and BP; when dreaming and penile/clitoral tumescence occur; may serve memory processing function - Beta waves

44

Thalamus

Major relay for all ascending sensory information except olfaction

45

VPL nucleus of thalamus

Input: Spinothalamic and dorsal column/medial lemniscus

Pain, temp; pressure, touch, vibration, proprioception

Destination: Primary Somatosensory cortex

46

VPM nucleus of thalamus

Input: Trigeminal and gustatory pathway

Face sensation, taste

Destination: Primary Somatosensory cortex

"Makeup goes on the face/ vpM"

47

LGN nucleus of thalamus

Input: CN II

Vision

Destination: Calcarine sulcus

"Lateral = Light"

48

MGN nucleus of thalamus

Input: Superior olive and inferior colliculus of tectum

Hearing

Destination: Auditory cortex of temporal lobe

"Medial = Music"

49

VL nucleus of thalamus

Input: Basal ganglia, cerebellum

Motor

Destination: Motor Cortex

50

Limbic System

Collection of neural structures involved in emotion, long term memory, olfaction, behavior modulation, ANS function

Structures include hippocampus, amygdala, fornix, mammillary bodies, cingulate cygrus

Responsible for the 5 F's

Feeding
Fleeing
Fighting
Feeling
Sex

51

Osmotic demyelination syndrome (Central Pontine Myelinosis)

Acute paralysis, dysarthria, dysphagia, diplopia, loss of consciousness

Can cause "locked-in syndrome"

Massive axonal demyelination in pontine white matter secondary to osmotic changes

Commonly iatrogenic, caused by overly rapid correction of hyponatremia. In contrast, correcting hypernatremia too quickly results in cerebral edema/herniation

Correcting Na too fast:
From low to high you pons will die (osmotic demyelination syndrome)

From high to low, your brain will blow (cerebral edema/herniation)

52

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 info to contralateral cortex to modulate movement. Output nerves = Purkinje cells - deep nuclei of cerebellum - contralateral cortex via superior cerebellar peduncle
2) Deep nuclei (lateral to medial) - Dentate, Emboliform, Globose, Fastigial (Dont Eat Greasy Foods)

Lateral lesions - voluntary movement of extemities; when injured, propensity to fall toward injured (ipsilateral) side

Medial lesions - lesions involving midline structures (vermal cortex, fastigial nuclei) and/or flocculonodular lobe - truncal ataxia (wide-based cerebellar gait), nystagmus, head tilting

Generally, midline lesions result in bilateral motor deficits axial and proximal limb musculature

53

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

Excitatory pathway - cortical inputs stimulate the striatum, stimulating the release of GABA, which disinhibits the thalamus via the GPi/SNr (increases motion)

Inhibitory pathway - cortical inputs stimulate the striatum, which disinhibits STN via GPe, and STN stimulates GPi/SNr to inhibit the thalamus (lowers motion)

Dopamine binds to D1, stimulating the excitatory pathway, and to D2, inhibiting the inhibitory pathway - increases motion

54

Athetosis

Slow, writhing movements; especially seen in fingers

Characteristic lesion: Basal ganglia (Huntington)

Writhing, snake-like movement

55

Chorea

Sudden, jerky, purposeless movements

Characteristic lesion: Basal ganglia (Huntington)

Chorea = dancing

56

Dystonia

Sustained, involuntary muscle contractions

Writer's cramp; blepharospasm (sustained eyelid twitch)

57

Essential tremor

High-frequency tremor with sustained posture (outstretched arms), worsened with movement or when anxious

Often familial. Patients often self-medicate with EtOH, which lowers tremor amplitude

Tx = B-blockers, primidone

58

Hemiballismus

Sudden, wild flailing of 1 arm +/- ipsilateral leg

Characteristic lesion: Contralateral subthalamic nucleus (lacunar stroke)

Contralateral lesion**

59

Intention tremor

Slow, zigzag motion when pointing/extending toward a target

Characteristic lesion: Cerebellar dysfunction

60

Myoclonus

Sudden, brief, uncontrolled muscle contraction

Jerks; hiccups; common in metabolic abnormalities such as renal and liver failure

61

Resting tremor

Uncontrolled movement of distal appendages (most noticeable in hands); tremor alleviated by intentional movement

Characteristic lesion: Parkinson Disease

occurs at rest; "pill rolling tremor" of Parkinson

62

Parkinson Disease

Degenerative disorder of CNS associated with Lewy Bodies (composed of alpha-synuclein - intracellular eosinophilic inclusions) and loss of dopaminergic neurons (depigmentation) of substantia nigra pars compacts

Parkinson TRAPS your body
T = tremor (pill-rolling tremor at rest)
R = rigidity (cogwheel)
A = Akinesia (or bradykinesia)
P = Postural instability
S = Shuffling gait

63

Huntington Disease

Autosomal dominant trinucleotide repeat disorder on chromosome 4

Symptoms manifest between ages 20-50; characterized by choreiform movements, aggression, depression, dementia (sometimes initially mistaken for substance abuse)

Increased dopamine
Decreased GABA
Decreased ACh

All in brain

Neuronal death via NMDA-R binding and glutamate toxicity. Atrophy of caudate nuclei with ex vacuo dilatation of frontal horns on MRI

Expansion of CAG repeats (anticipation)

Caudate loses Ach and Gaba (CAG)

64

Aphasia - general

higher order inability to speak (language deficit).

Dysarthria = motor inability to speak (movement deficit)

65

Broca aphasia

Nonfluent with intact comprehension and impaired repetition.

Broca area - inferior frontal gyrus of frontal lobe

Broca = Broken Boca

66

Wernicke aphasia

Fluent with impaired comprehension and repetition

Wernicke area - superior temporal gyrus of temporal lobe

Wernicke is wordy but makes no sense. Wernicke = what??

67

Conduction aphasia

Poor repetition but fluent speech, intact comprehension. Can be caused by damage to arcuate fasciculus

Can't repeat phrases such as "No ifs, ands, or buts"

68

Global aphasia

Nonfluent aphasia with impaired comprehension

Arcuate fasciculus, Broca, and Wernicke areas affected

69

Transcortical motor aphasia

Nonfluent aphasia with good comprehension and intact repetition

70

Transcortical sensory aphasia

Poor comprehension with fluent speech and intact repetition

71

Mixed transcortical aphasia

Nonfluent speech; poor comprehension, intact repetition

Broca and Wernicke areas involved; arcuate fasiculus not involved

72

Bilateral amygdala lesion

Kluver-Bucy Syndrome - disinhibited behavior (hyperphagia, hypersexuality, hyperorality)

Associated with HSV-1

73

Frontal lobe lesion

Disinhibition and deficits in concentration, orientation, judgement; may have reemergence of primitive reflexes

74

Nondominant parietal-temporal cortex lesion

Hemispatial neglect syndrome (agnosia of the contralateral side of the world)

75

Dominant parietal-temporal cortex lesion

Agraphia, acalculia, finger agnosia, left-right disorientation

Gerstmann Syndrome

76

Reticular activating system (midbrain) lesion

Reduced levels of arousal and wakefulness (coma)

77

Mammillary bodies (bilateral) lesion

Wernicke-Korsakoff Syndrome - confusion, ophthalmoplegia, ataxia; memory loss (anterograde and retrograde amnesia), confabulation, personality changes.

Associated with thiamine (B1) deficiency and excesive EtOH use; can be precipitated by giving glucose without B1 to a B1 deficient patient.

Wernicke problems come in a CAN of beer = Confusion, Ataxia, Nystagmus

78

Basal ganglia lesion

May result in tremor at rest, chorea, athetosis

Parkinson, Huntington

79

Cerebellar hemisphere lesion

Intention tremor, limb ataxia, loss of balance; damage to cerebellum leads to ipsilateral deficits; fall toward side of lesion

"Cerebellar hemispheres are laterally located - affect lateral limbs"

80

Cerebellar vermis lesion

Truncal ataxia, dysarthria

"Vermis is centrally located - affects central body"

81

Subthalamic nucleus lesion

Contralateral hemiballismus

82

Hippocampus (bilateral) lesion

Anterograde amnesia - inability to make new memories

83

Paramedian pontine reticular formation lesion

Eyes look away from side of lesion

84

Frontal eye fields lesion

Eyes look toward lesion

85

Regulation of cerebral perfusion

Brain perfusion relies on tight autoregulation. Cerebral perfusion is primarily driven by P CO2 (P O2 also modulates perfusion in severe hypoxia)

Therapeutic hyperventilation (lowers P CO2) helps reduce ICP in case of acute cerebral edema (stoke, trauma) via vasoconstriction. Fainting in panic attacks due to reduce perfusion

Cerebral perfusion relies on a pressure gradient between mean arterial pressure (MAP) and ICP. Lower BP or higher ICP leads to reduced cerebral perfusion pressure (CPP)

CPP = MAP - ICP

If CPP = 0 there is no cerebral perfusion - brain death

86

Middle Cerebral Artery stroke

1) Motor cortex - upper limb and face
Contralateral paralysis - upper limb and face

2) Sensory cortex - upper limb and face
Contralateral loss of sensation - upper limb and face

3) Temporal lobe (Wernicke area); Frontal lobe (Broca area) - Aphasia if in dominant (usually left) hemisphere. Hemineglect if lesion affects nondominant (usually right) side

87

Anterior Cerebral Artery stroke

1) Motor cortex - lower limb
Contralateral paralysis

2) Sensory cortex - lower limb
Contralateral loss of sensation

88

Lenticulostriate artery stroke

Striatum, internal capsule - Contralateral hemiparesis/hemiplegia

Common location of lacunar infarcts, secondary to unmanaged HTN

89

Anterior Spinal Artery stroke

1) Lateral corticospinal tract - contralateral hemiparesis - upper and lower limbs

2) Medial lemniscus - reduced contralateral proprioception

3) Caudal medulla - hypoglossal nerve - Ipsilateral hypoglossal dysfunction (tongue deviates ipsilaterally)

Stroke commonly bilateral

Medial medullary syndrome - caused by infarct of paramedian branches of ASA and vertebral arteries

90

Posterior Inferior Cerebellar Artery (PICA) stroke

Lateral medulla - vestibular nuclei, lateral spinothalamic tract, spinal trigeminal nucleus, nucleus ambiguus, sympathetic fibers, inferior cerebellar peduncle

Vomiting, vertigo, nystagmus; reduced pain and temp sensation from ipsilateral face and contralateral body; dysphagia, hoarseness, reduced gag reflex; ipsilateral Horner Syndrome; ataxia, dysmetria

Lateral Medullary (Wallenberg) Syndrome - Nucleus ambiguus effects are specific to PICA lesions

"Don't pick a (PICA) horse (hoarseness) that can't eat (dysphagia)"

91

Anterior Inferior Cerebellar Artery (AICA) stroke

1) Lateral pons - cranial nerve nuclei; vestibular nuclei, facial nucleus, spinal trigeminal nucleus, cochlear nuclei, sympathetic fibers

Vomiting, vertigo, nystagmus, Paralysis of face, reduced lacrimation, salivation, lower taste from anterior 2/3 of tongue.

Ipsilateral reduced pain and temp of the face, contralateral reduced pain and temp of the body

2) Middle and inferior cerebellar peduncles

Ataxia, dysmetria

Lateral pontine syndrome = facial nucleus effects are specific to AICA lesions "Facial droop means AICA's pooped"

92

Posterior Cerebral Artery stroke

Occipital cortex, visual cortex - contralateral hemianopia with macular sparing

93

Basilar artery stroke

Pons, medulla, lower midbrain, corticospinal and corticobulbar tracts, ocular cranial nerve nuclei, paramedian pontine reticular formation

Preserved consciousness and blinking, quadriplegia, loss of voluntary facial, mouth, and tongue movements

"Locked-in syndrome"

94

Anterior Communicating Artery stroke

Most common lesion is aneurysm. Can lead to stroke. Saccular (berry) aneurysm can impinge cranial nerves

Visual field defects

Defects are typically aneurysms, not strokes

95

Posterior Communicating Artery stroke

Common site of saccular aneurysm

CN 3 palsy - eye is "down and out" with ptosis and mydriasis

Lesions are typically aneurysm not strokes

96

Saccular (Berry) Aneurysm

Occurs at bifurcations in the circle of Willis. Most common site is junction of anterior communicating artery and anterior cerebral artery

Rupture (most common complication) leads to subarachnoid hemorrhage ("worst headache of my life") or hemorrhagic stroke

Can also cause bitemporal hemianopia via compression of optic chiasm

Associated with:
1) ADPKD
2) Ehlers-Danlos

Other risk factors: advanced age, HTN, smoking, race (more in blacks)

97

Charcot-Bouchard microaneurysm

Associated with chronic HTN; affects small vessels (e.g. in basal ganglia, thalamus)

98

Central post-stroke pain syndrome

Neuropathic pain due to thalamic lesions. Initial paresthesias followed in weeks to months by allodynia (ordinarily painless stimuli cause pain) and dysesthesia

Occurs in 10% of stroke patients

99

Epidural hematoma

Rupture of middle meningeal artery (branch of maxillary artery) often secondary to fracture of temporal bone.

Lucid interval.

Rapid expansion under systemic arterial pressure leads to transtentorial herniation, CN 3 palsy

CT shows biconvex (lentiform), hyperdense blood collection not crossing suture lines. Can cross falx, tentorium

100

Subdural hematoma

Rupture of bridging veins. Slow venous bleeding (less pressure = hematoma develops over time)

Seen in elderly, alcoholics, blunt trauma, shaken baby (predisposing factors: brain atrophy, shaking, whiplash)

Crescent-shaped hemorrhage that CROSSES SUTURE LINES. Midline shift. Cannot cross falx, tentorium

101

Subarachnoid hemorrhage

Rupture of an aneurysm (such as berry/saccular aneurysm, as seen in Ehlers-Danlos, ADPKD) or arteriovenous malformation.

Rapid time course

Patient complains of "worst headache of my life (WHOML)"

Bloody or yellow (xanthochromic) spinal tap. 2-3 days afterward, risk of vasospasm due to blood breakdown (not visible on CT, treat with nimodipine) and rebleed (visible on CT)

102

Intraparenchymal (hypertensive) hemorrhage

Most commonly caused by systemic HTN. Also seen with amyloid angiopathy (recurrent lobar hemorrhagic stroke in elderly), vasculitis, neoplasm.

Typically occurs in basal ganglia and internal capsule (Charcot-Bouchard aneurysm of lenticulostriate vessels), but can be lobar

103

Ischemic brain disease/stroke

Irreversible damage begins after 5 minutes of hypoxia

Most vulnerable: hippocampus*, neocortex, cerebellum, watershed areas. Irreversible neuronal injury

Stroke imaging: Noncontrast CT to exclude hemorrhage (before tPA can be given). CT detect ischemic changes in 6-24hrs. Diffusion-weighted MRI can detect ischemia within 3-30 mins.

Histo features:

12-48hrs = red neurons

24-72 hrs = Necrosis + neutrophils

3-5 days = Macrophages (microglia)

1-2 weeks = Reactive gliosis + vascular proliferation

> 2 weeks = Glial scar

104

Hemorrhagic stroke

Intracranial bleeding, often due to HTN, anticoagulation, cancer (abnormal vessels can bleed).

May be secondary to ischemic stroke followed by reperfusion (increased vessel fragility)

Basal ganglia are most common site of intracerebral hemorrhage

105

Ischemic stroke

Acute blockage of vessels leads to disruption of blood flow and subsequent ischemia leading to liquefactive necrosis

3 types:

1) Thrombotic - due to a clot forming directly at site of infarction (commonly MCA), usually over an atherosclerotic plaque

2) Embolic - embolus from another part of the body obstructs vessel. Can affect multiple vascular territories. Examples: Atrial fibrillation; DVT will patent foramen ovale

3) Hypoxic- due to hypoperfusion or hypoxemia. Common during cardiovascular surgeries, tends to affect watershed areas

tx = tPA (if within 3-4.5 hr of onset and no hemorrhage/risk of hemorrhage). Reduce risk with medical therapy (aspirin, clopidogrel); optimum control of BP, blood sugars, lipids; and treat conditions that increase risk (AFib)

106

Ventricular system

Lateral ventricle goes to 3rd ventricle via right and left interventricular foramina of Monro

3rd goes to 4th via cerebral aqueduct (of Sylvius)

4th to subarachnoid space via:
- Foramina of Luschka (Lateral)
- Foramen of Magendie (Medial)

CSF is made by ependymal cells of choroid plexus; it is reabsorbed by arachnoid granulations and then drains into dural venous sinuses

107

Idiopathic intracranial HTN (pseudotumor cerebri)

Increased ICP with no apparent cause on imaging (hydrocephalus, obstruction of CSF outflow)

Patients present with HAs, diplopia (usually from CN 6 palsy), no mental status alterations

Papilledema seen on exam. Risk factors include being a woman of childbearing age, vitamin A excess, danazol. Lumbar puncture reveals higher opening pressure and provides HA relief.

Tx = weight loss, acetazolamide, topiramate, invasive procedures for refractory cases (repeat lumbar punctures, CSF shunt placement, optic nerve fenestration surgery)

108

Communicating hydrocephalus

Nonobstructive

Lower CSF absorption by archnoid granulations leads to higher ICP, papilledema, herniation (arachnoid scarring post-meningitis)

109

Normal Pressure hydrocephalus

Nonobstructive

Affects the elderly; idiopathic; CSF pressure elevated only episodically; does not result in increased subarachnoid space volume.

Expansion of ventricles distorts the fibers of the corona radiata leads to triad of urinary incontinence, ataxia, and cognitive dysfunction (sometimes reversible).

"Wet, wobbly, wacky"

110

Noncommunicating hydrocephalus

Obstructive

Caused by structural blockage of CSF circulation within ventricular system (stenosis of aqueduct of Sylvius; colloid cyst blocking foramen of Monro)

111

Ex Vacuo Ventriculomegaly

Hydrocephalus mimic

Appearance of increased CSF on imaging, is actually due to decreased brain tissue (neuronal atrophy) (e.g. Alzheimer, advanced HIV, Pick Disease)

ICP is normal; triad is not seen

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Spinal nerves

There are 31 pairs of spinal nerves in total - 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal

C1-C7 nerves exit above the corresponding vertebra
C8 exits below C7 and above T1

All other spinal nerves exit below (L2 exits below 2nd lumbar vertebra for example)

Vertebral disc herniation - nucleus pulposus (soft central disc) herniates through annulus fibrosus (outer ring); usually occurs posterolaterally at L4-L5 or L5-S1

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Spinal cord - lower extent

In adults, spinal cord extends to lower border of L1-L2 vertebrae. Subarachnoid space (which contains the CSF) extends to lower border of S2 vertebra. Lumbar puncture is usually performed between L3-L4 or L4-L5 (level of cauda equina)

Goal of lumbar puncture is to obtain sample of CSF without damaging spinal cord. To keep the cord "alive", keep the spinal needle between L3 and L5.

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Dorsal column

Ascending - it synapses then crosses

**Pressure, vibration, fine touch, and proprioception**

1) 1st order neuron = sensory nerve ending goes to cell body in DRG then enters spinal cord and ascends ipsilaterally in dorsal column

2) Synapse 1 = Ipsilateral nucleus cuneatus (upper body/arms) or gracilis (lower body/legs) in medulla

3) 2nd order neuron = Decussates in medulla then ascends contralaterally in medial lemniscus

4) Synapse 2 = VPL (thalamus)

5) 3rd order neuron = Sensory cortex

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Spinothalamic tract

AKA "anterolateral system"

Ascending - it synapses then crosses

Lateral = Pain, Temperature
Anterior = Crude Touch, Pressure

1) 1st order neuron = Sensory nerve ending (Adelta and C fibers) (cell body in DRG). Then enters spinal cord.

2) Synapse 1 = Ipsilateral gray matter (spinal cord)

3) 2nd order neuron = Decussates at anterior white commissure then ascends contralaterally

4) Synapse 2 = VPL (Thalamus)

5) 3rd order neuron = Sensory cortex

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Lateral Corticospinal tract

Descending

Voluntary movement of contralateral limbs

1) 1st order neuron = UMN: cell body in primary motor cortex descends ipsilaterally (through internal capsule), most fibers decussate at caudal medulla (pyramidal decussation). Then they descend contralaterally

2) First synapse = Cell body of anterior horn (spinal cord)

3) 2nd order neuron = LMN: leaves spinal cord

4) Synapse 2 = NMJ (neuromuscular junction)

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UMN vs LMN

1) Weakness = UMN or LMN

2) Atrophy = LMN

3) Fasciculations = LMN

4) Reflexes = Increased (UMN) or decreased (LMN)

5) Tone = Increased (UMN) or decreased (LMN)

6) Babinski = UMN

7) Spastic paralysis = UMN

8) Flaccid paralysis = LMN

9) Clasp knife spasticity = UMN

Lower = everything lowered (less muscle mass, less muscle tone, lower reflexes, downgoing toes)

Upper = everything up (tone, DTR, toes)

Fasciculations = muscle twitches

Positive Babinsky is normal in infants

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Werdnig-Hoffmann Disease

Poliomyelitis and spinal muscular atrophy

LMN lesions only, due to destruction of anterior horns; flaccid paralysis

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MS

Due to demyelination; mostly white matter of cervical region; random and asymmetric lesions, due to demyelination; scanning speech, intention tremor, nystagmus

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ALS

Combined UMN and LMN deficits with no sensory or oculomotor deficits; both UMN and LMN signs.

Can be caused by defect in superoxide dismutase I

Commonly presents as fasciculations with eventual atrophy and weakness of hands; fatal

Riluzole treatment modestly increases survival by lowering presynaptic glutamate release

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Complete occlusion of anterior spinal artery

Spares dorsal columns and Lissauer tract; Upper thoracic ASA territory is watershed area, as artery of Adamkiewicz supplies ASA below T8

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Tabes Dorsalis

Caused by tertiary Syphilis. Results from degeneration (demyelination) of dorsal columns and roots - impaired sensation and proprioception, progressive sensory ataxia (inability to sense or feel the legs causes poor coordination)

Associated with Charcot joints, shooting pain, Argyll Robertson pupils

Exam will demonstrate absence of DTRs and (+) Romberg sign

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Syringomyelia

Syrinx expands and damages anterior white commissure of spinothalamic tract (2nd order neurons) - bilateral loss of pain and temp sensation (usually C8-T1); seen with Chiari I malformations; can expand and affect other tracts

124

Vitamin B12 Deficiency

Subacute combined degeneration - demyelination of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts

Ataxic gait, parasthesia, impaired position and vibration sense

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Poliomyelitis

Caused by poliovirus (fecal-oral transmission). Replicates in oropharynx and small intestine before spreading via bloodstream to CNS. Infection causes destruction of cells in anterior horn of spinal cord (LMN death)

Symptoms = LMN lesion signs: weakness, hypotonia, flaccid paralysis, fasciculations, hyporeflexia, muscle atrophy. Signs of infection: malaise, HA, fever, nausea, etc

Findings = CSF with high WBCs and slight elevation of protein (with no change in CSF glucose). Virus recovered from stool or throat.

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Spinal muscular atrophy (Werdnig-Hoffman Disease)

Congenital degeneration of anterior horn of spinal cord leads to LMN lesion. "Floppy baby" with marked hypotonia and tongue fasciculations. Infantile type has median age of death of 7 months.

Autosomal recessive

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Friedrich Ataxia

Autosomal recessive trinucleotide repeat disorder (GAA) on chromosome 9 in gene that encodes frataxin (iron binding protein)

Leads to impairment in mitochondrial functioning. Degeneration of multiple spinal cord tracts causes muscle weakness and loss of DTRs, vibratory sense, proprioception

Staggering gait, frequent falling, nystagmus, dysarthria, pes cavus, hammer toes, diabetes mellitus, hypertrophic cardiomyopathy (cause of death).

Presents in childhood with kyphoscoliosis

"Friedreich is fratastic (frataxin): he's your favorite frat brother, always staggering and falling but has a sweet, big heart"

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Brown-Sequard Syndrome

Hemisection of spinal cord. Findings:
1) Ipsilateral UMN signs below level of lesion (due to corticospinal tract damage)

2) Ipsilateral loss of tactile, vibration, proprioception sense below level of lesion (due to damage to dorsal column)

3) Contralateral pain and temp loss below level of lesion (due to spinothalamic tract damage)

4) Ipsilateral loss of all sensation at level of lesion

5) Ipsilateral LMN signs (flaccid paralysis) at level of lesion

If lesion occurs above T1, patient may present with Horner syndrome due to damage of oculosympathetic pathway

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Landmark dermatomes

C2 = posterior half of a skull "cap"

C3 = high turtleneck shirt

C4 = low collar shirt

T4 = at the nipple - "T4 at the teat pore"

T7 = at the xiphoid process

T10 = at the umbilicus (important for early appendicitis pain referral)

L1 = at the inguinal ligament - "L1 = IL"

L4 = includes the kneecaps - "Down on ALL 4's"

S2, S3, S4 = erection and sensation of penile and anal zones - "S2, 3, 4 keep the penis off the floor"

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Clinical reflexes

Biceps = C5 nerve root

Triceps = C7 nerve root

Patella = L4 nerve root

Achilles = S1 nerve root

Reflexes count up in order:

S1,2 - "buckle my shoe" - Achilles

L3,4 - "kick the door" - Patellar

C5,6 - "pick up sticks" - biceps

C7,8 - "lay them straight" - triceps

L1,2 - "testicles move" - cremaster

S3,4 - "winks galore" - anal wink

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Primitive reflexes

CNS reflexes that are present in a healthy infant, but are absent in a neurologically intact adult

Normally disappear within 1st year of life. These primitive reflexes are inhibited by a mature/developing frontal lobe. They may remerge in adults following frontal lobe lesions - loss of inhibition of these reflexes

1) Moro reflex - "Hang on for life" reflex - abduct/extend arms when startled, and then draw together

2) Rooting reflex - Movement of head toward one side if cheek or mouth is stroked (nipple seeking)

3) Sucking reflex - Sucking response when roof of mouth is touched

4) Palmar reflex - curling of fingers if palm is stroked

5) Plantar reflex - Dorsiflexion of large toe and fanning of other toes with plantar stimulation

"Babinski" - presence of this reflex in an adult, which may signify UMN lesion

6) Galant reflex - Stroking along one side of the spine while newborn is in ventral suspension (face down) causes lateral flexion of lower body toward stimulated side

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Brain stem - dorsal structures

Pineal gland - melatonin secretion, circadian rhythms

Superior colliculi - conjugate vertical gaze center

Inferior colliculi - auditory

Parinaud Syndrome - paralysis of conjugate vertical gaze due to lesion in superior colliculi (stroke, hydrocephalus, pinealoma)

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Cranial nerve nuclei

Located in tegmentum portion of brain stem (btw dorsal and ventral portions)

Midbrain = nuclei of 3,4

Pons = nuclei of 5,6,7,8

Medulla = nuclei of 9,10,12

Spinal cord = nucleus of 11

Lateral nuclei = sensory (aLar plate)
----- Sulcus Limitans -----
Medial nuclei = motor (basal plate

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Cranial nerve and vessel pathways

Cribiform plate = 1

Middle cranial fossa = 2-6 - through sphenoid bone
- Optic canal = 2, ophthalmic artery, central retinal vein

- Superior orbital fissure = 3, 4, V1, 6, ophthalmic vein, sympathetic fibers

- Foramen Rotundum = V2

- Foramen Ovale = V3

- Foramen Spinosum = Middle meningeal artery

Posterior cranial fossa = 7-12 - through temporal or occipital bone
- Internal auditory meatus = 7,8

- Jugular foramen = 9, 10, 11, jugular vein

- Hypoglossal canal = 12

- Foramen magnum = spinal roots of 11, brain stem, vertebral arteries.

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Cranial nerves

1) Olfactory = Smell - only one without thalamic relay to cortex (S)

2) Optic = Sight (S)

3) Oculomotor = Eye movements (SR, IR, MR, IO), pupillary constriction (sphincter pupillae: Edinger-Westphal nucleus, muscarinic receptors), accommodation, eyelid opening (levator palpebrae) (M)

4) Trochlear = Eye movement (SO) (M)

5) Trigeminal = Mastication, facial sensation (ophthalmic, maxillary, mandibular divisions), somatosensation from anterior 2/3 of tongue (B)

6) Abducens = Eye movements (LR) (M)

7) Facial = Facial movement, taste from anterior 1/3 of tongue, lacrimation, salivation (submandibular and sublingual glands), eyelid closing (orbicularis oculi), stapedius muscle in ear (note: nerve courses through the parotid gland, but does not innervate it) (B)

8) Vestibulocochlear = Hearing, balance (S)

9) Glossopharyngeal = Taste and somatosensation from posterior 1/3 of tongue, swallowing, salivation (parotid gland), monitoring carotid body and sinus chemo-and baroreceptors, and stylopharyngeus (elevates pharynx, larynx) (B)

10) Vagus = Taste from epiglottic region, swallowing, soft palate elevation, midline uvula, talking, coughing, thoracoabdominal viscera, monitoring aortic arch chem and baroreceptors (B)

11) Accessory = Head turning, shoulder shrugging (SCM, Trapezius) (M)

12) Hypoglossal = Tongue movement (M)

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

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Vagal nuclei

1) Nucleus Solitarius - Visceral sensory info (taste, baroreceptors, gut distention) - CN 7, 9, 10

2) Nucleus Ambiguus - Motor innervation of pharynx, larynx, upper esophagus (swallowing, palate elevation) - CN 9, 10, 11 (cranial portion)

3) Dorsal motor nucleus - Sends autonomic (parasympathetic) fibers to heart, lungs, upper GI - CN 10

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Cranial nerve reflexes

1) Corneal
Afferent = V1 Ophthalmic (nasociliary branch)
Efferent = VII (temporal branch: orbicularis oculi)

2) Lacrimation
Afferent = V1 (loss of reflex does not preclude emotional tears)
Efferent = VII

3) Jaw jerk
Afferent = V3 (sensory - muscle spindle from masseter)
Efferent = V3 (motor - masseter)

4) Pupillary
Afferent = II
Efferent = III

5) Gag
Afferent = IX
Efferent = X

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Common cranial nerve lesions

1) CN V motor lesion - jaw deviates toward side of lesion due to unopposed force from the opposite pterygoid muscle

2) CN X lesion - Uvula deviates away from side of lesion. Weak side collapses and uvula points away

3) CN XI lesion - Weakness turning head to contralateral side of lesion (SCM). Shoulder droop on side of lesion (trapezius)

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

4) CN XII lesion (LMN) - Tongue deviates toward side of lesion ("lick your wounds") due to weakened tongue muscles on affected side

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Cavernous sinus

Collection of venous sinuses on either side of pituitary. Blood from eye and superficial cortex goes to the cavernous sinus then to internal jugular vein

CN 3, 4, V1, 6 and sometimes V2 plus postganglionic sympathetic pupillary fibers en route to orbit all pass through cavernous sinus. Cavernous portion of internal carotid artery is also here.

Nerves that control extraocular muscles (plus V1 and V2) pass through the cavernous sinus

Cavernous Sinus Syndrome - presents with variable ophthalmoplegia, decreased corneal sensation, Horner syndrome and occasional decreased maxillary sensation. Secondary to pituitary tumor mass effect, carotid-cavernous fistula, or cavernous sinus thrombosis related to infection. CN 6 is most susceptible to injury

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Outer ear

Visible portion of ear (pinna), includes auditory canal and eardrum. Transfers sound waves via vibration of eardrum

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Middle ear

Air-filled space with 3 bones called the ossicles (malleus, incus, stapes). Ossicles conduct and amplify sound from eardrum to inner ear

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Inner ear

Snail-shaped, fluid-filled cochlea. Contains basilar membrane that vibrates secondary to sound waves.

Vibration transduced via specialized hair cells - auditory nerve signaling - brain stem

Each frequency leads to vibration at specific location on basilar membrane (tonotopy)

Low frequency heard at apex near helicotrema (wide and flexible)
High frequency heard best at base of cochlea (thin and rigid)

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Hearing loss

1) Conductive - Rhinne abnormal (bone > air). Weber localizes to affected ear

2) Sensorineural - Rhinne normal (air > bone). Weber localizes to unaffected ear

3) Noise-induced - Damage to sterociliated cells in organ of Corti; loss of high frequency hearing 1st; sudden extremely loud noises can produce hearing loss due to tympanic membrane rupture

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Cholesteatoma

Overgrowth of desquamated keratin debris within middle ear space; may erode ossicles, mastoid air cells causing conductive hearing loss

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Facial lesions

1) UMN - lesion of motor cortex or connection btw cortex and facial nucleus. Contralateral paralysis of lower face; forehead spared due to bilateral UMN innervation

2) LMN - Ipsilateral paralysis of upper AND lower face

3) 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 Palsy); gradual recovery in most cases

Associated with Lyme Disease, herpes simplex and (less common) herpes zoster (Ramsay Hunt Syndrome), sarcoidosis, tumors, diabetes

Tx = corticosteroids

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Mastication muscles

3 muscles close jaw: Masseter, Temporalis, Medial pytergoid

1 opens: lateral pytergoid

All are innervated by trigeminal nerve (V3)

"It takes more muscles to keep your mouth shut"

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Refractive errors

Common cause of impaired vision, correctible with glasses

1) Hyperopia - eye too short for refractive power of cornea and lens - light focused behind retina

2) Myopia - eye too long for refractive power of cornea and lens - light focused in front of retina

3) Astigmatism - abnormal curvature of cornea - different refractive power at different axes

4) Presbyopia - Age-related impaired accommodation (focusing on near objects), possibly due to decreased lens elasticity. Often necessitates "reading glasses"

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Cataract

Painless, often bilateral, opacification of lens leading to decrease in vision.

Risk factors: Age,, smoking, EtOH, excessive sunlight, prolonged corticosteroid use, classic galactosemia, galactokinase deficiency. diabetes mellitus (sorbitol), trauma, infection

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Glaucoma - general

Optic disc atrophy with characteristic cupping (thinning of outer rim of optic nerve head versus normal), usually with elevated IOP and progressive peripheral visual field loss

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Open angle glaucoma

Associated with age, blacks, family history. Painless, more common in US

Primary - cause unclear

Secondary - blocked trabecular meshwork from WBCs (uveitis), RBCs (vitreous hemorrhage), retinal elements (retinal detachment)

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Closed/Narrow angle glaucoma

Primary - enlargement of forward movement of lens against central iris (pupil margin) leads to obstruction of normal aqueous flow through pupil causing fluid build up behind iris, pushing peripheral iris against cornea and impeding flow through trabecular meshwork

Secondary - hypoxia from retinal disease (diabetes mellitus, vein occlusion) induces vasoproliferation in iris that contracts angle

Chronic closure - often asymptomatic with damage to optic nerve and peripheral vision

Acute closure - true ophthalmic emergency. Increased IOP pushes iris forward leading to angle closing abruptly. Very painful, red eye, sudden vision loss, halos around lights, rock-hard eye, frontal headache

Do not give Epinephrine bc of its mydriatic effect

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Uveitis

Inflammation of uvea (iritis aka interior uveitis, choroiditis, aka posterior uveitis). May have hypopyon (accumulation of pus in anterior chamber) or conjunctival redness.

Associated with systemic inflammatory disorders (sarcoidosis, RA, juvenile idiopathic arthritis, HLA-B27 associated conditions)

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Age related macular degeneration

Degeneration of macula (central area of retina). Causes distortion (metamorphopsia) and eventual loss of central vision (scotomas)

Dry (nonexudative, > 80%) - deposition of yellowish extracellular material in and beneath Bruch membrane and retinal pigment epithelium ("drusen") with gradual decrease in vision. Prevent progression with multivitamin and antioxidant supplements

Wet (exudative, 10-15%) - rapid loss of vision due to bleeding secondary to choroidal neovascularization. Treat with anti-VEGF (vascular endothelial growth factor) injections (ranibizumab) or laser.

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Diabetic retinopathy

Retinal damage due to chronic hyperglycemia. 2 types.

Nonproliferative - damaged capillaries leak blood causing lipids and fluid to seep into retina. This causes hemorrhage and macular edema. Tx = blood sugar control, macular laser

Proliferative - chronic hypoxia results in new blood vessel formation with resultant traction on retina. Tx = peripheral retinal photocoagulation, anti-VEGF (bevacizumab)

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Retinal vein occlusion

Blockage of central or branch retinal vein due to compression from nearby arterial atherosclerosis

Retinal hemorrhage and venous engorgement, edema in affected area

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Retinal detachment

Separation of neurosensory layer of retina (photreceptor layer with rods and cones) from outermost pigmented epithelium (normally shields excess light, supports retina) - degeneration of photoreceptors - vision loss.

May be secondary to retinal breaks, diabetic traction, inflammatory effusions. Visualized on fundoscopy by the splaying and paucity of retinal vessels.

Breaks more common in patients with high myopia and are often preceded by posterior vitreous detachment ("flashes" and "floaters") and eventual monocular loss of vision like a "curtain drawn down."

Surgical emergency

157

Central retinal artery occlusion

Acute, painless monocular vision loss. Retina cloudy with attenuated vessels and "cherry-red" spots at fovea (center of macula)

158

Retinitis pigmentosa

Inherited retinal degeneration. Painless, progressive vision loss beginning with night blindness (rods affected first).

Bone spicule-shaped deposits around macula

159

Retinitis

Retinal edema and necrosis leading to scar. Often viral (CMV, HSV, HZV)

Associated with immunosuppression

160

Papilledema

Optic disc swelling (usually bilateral) due to increased ICP (secondary to mass effect).

Enlarged blind spot and elevated optic disc with blurred margins seen on fundoscopic exam

161

Miosis

Constriction, parasympathetic

1st neuron: Edinger-Westphal nucleus to ciliary ganglion via CN 3

2nd neuron: short ciliary nerves to pupillary sphincter muscles

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Pupillary light reflex

Light in either retina sends a signal via CN 2 to pretectal nuclei in midbrain that activates bilateral Edinger-Westphal nuclei; pupils contract bilaterally (consensual reflex)

Result: illumination of 1 eye results in bilateral pupillary constriction

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Mydriasis

Dilation, sympathetic

1st neuron: hypothalamus to ciliospinal center of Budge (C8-T2)

2nd neuron: exit at T1 to superior cervical ganglion (travels along cervical sympathetic chain near lung apex, subclavian vessels)

3rd neuron: plexus along internal carotid, through cavernous sinus; enters orbit as long ciliary nerve to pupillary dilator muscles. Sympathetic fibers also innervate smooth muscle of eyelids (minor retractors) and sweat glands of forehead and face

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Marcus Gunn pupil

Afferent pupillary defect - due to optic nerve damage or severe retinal injury.

Decreased bilateral pupillary constriction when light is shone in affected eye relative to unaffected eye. Tested with "swinging flashlight test"

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Horner Syndrome

Sympathetic denervation of face

Ptosis (slight drooping of eyelid: superior tarsal muscle)

Anhidrosis (absence of sweating) and flushing (rubor) of affected side of face

Miosis (pupil constriction)

Associated with lesion of spinal cord above T1 (Pancoast tumor, Brown-Sequard [cord hemisection], late-stage syringomyelia)

Any interruption results in Horner Syndrome

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Ocular motility

CN 6 innervates LR

CN 4 innervates SO

CN 3 innervates the rest

LR6SO4

SO abducts, intorts, and depresses while adducted

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CN 3 damage

CN 3 has both motor (central) and parasympathetic (peripheral) components.

Motor output to ocular muscles - affected primarily by vascular disease (diabetes mellitus: glucose becoming sorbitol) due to depressed diffusion of oxygen and nutrients to the interior fibers from compromised vasculature that resides on outside of nerve. Signs: ptosis, "down and out" gaze

Parasympathetic output - fibers on the periphery are 1st affected by compression (posterior communicating artery aneurysm, uncal herniation). Signs: diminished or absent pupillary light reflex, "blown pupil" often with "down and out" gaze

168

CN 4 damage

Eye moves upward, particularly with contralateral gaze and head tilt toward the side of the lesion (problems going down stairs, may present with compensatory head tilt in the opposite direction)

169

CN 6 damage

Medially directed eye that cannot abduct

170

Internuclear ophthalmoplegia

Medial longitudinal fasciculus (MLF): pair of tracts that allows for crosstalk between CN 6 and CN 3 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 (bilateral classically seen in MS)

Lesion in MLF = internuclear ophthalmoplegia (INO), a conjugate horizontal gaze palsy. Lack of communication such that when CN 6 nucleus activates ipsilateral lateral rectus, contralateral CN3 nucleus does not stimulate medial rectus to fire. Abducting eye gets nystagmus (CN 6 overfires to stimulate CN 3). Convergence normal.

When looking left, the left nucleus of CN 6 fires, which contracts the left lateral rectus and stimulates the contralateral (right) nucleus of CN 3 via the right MLF to contract the right medial rectus

Directional term (right INO, left INO) - refers to which eye is paralyzed

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Dementia - general

A decrease in cognitive ability, memory, or function with intact consciousness

172

Alzheimer Disease

Most common cause of dementia in elderly. Down Syndrome patients have an increased risk of developing Alzheimer

Familial form (10%) associated with the following altered proteins:
1) ApoE2: lower risk
2) ApoE4: higher risk
3) APP, presenilin-1, presenilin-2: higher risk of early onset

Widespread cortical atrophy. Narrowing of gyri and widening of sulci.

Lower ACh

Senile plaques in gray matter: extracellular B-amyloid core; may cause amyloid angiopathy leading to intracranial hemorrhage; Amyloid-B synthesized by cleaving amyloid precursor protein (APP)

Neurofibrillary tangles: intracellular, hyperphosphorylated tau protein = insoluble cytoskeletal elements; number of tangles correlates with degree of dementia

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Frontotemporal Dementia

Dementia, aphasia, parkinsonian aspects; change in personality

Spares parietal lobe and posterior 2/3 of superior temporal gyrus

Also called Pick Disease. Note the Pick bodies: silver-staining spherical tau protein aggregates

Frontotemporal atrophy

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Lewy Body Dementia

Initially dementia and visual hallucinations followed by parkinsonian features

alpha-synuclein defect (Lewy Bodies, primarily cortical)

175

Creutzfeldt-Jakob Disease

Rapidly progressive (weeks to months) dementia with myoclonus ("startle myoclonus")

Spongiform cortex

Prions (PrPc to PrPsc sheet [B-pleated sheet resistant to proteases])

176

Other causes of dementia

Multi-infarct (aka vascular, 2nd most common cause of dementia in elderly)

Syphilis

HIV

Vitamins B1, B3, or B12 deficiency

Wilson Disease

Normal pressure hydrocephalus

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Multiple Sclerosis - general

Autoimmune inflammation and demyelination of CNS (brain and spinal cord). Patients can present with optic neuritis (sudden loss of vision resulting in Marcus Gunn pupils), INO, hemiparesis, hemisensory symptoms, bladder/bowel incontinence

Relapsing and remitting course. Most often affects women in their 20s and 30s; more common in whites living further from equator

Charcot classic triad of MS is a SIN:
Scanning speech
Intention tremor (also Incontinence and INO)
Nystagmus

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Multiple Sclerosis - Findings and Tx

Increased protein (IgG) in CSF. Oligoclonal bands are diagnostic

MRI is gold standard. Periventricular plaques (areas of oligodendrocyte loss and reactive gliosis) with destruction of axons. Multiple white matter lesions separated in space and time.

Tx: slow progression with disease-monitoring therapies (B-interferon, natalizumab).

Treat acute flares with IV steroids.

Symptomatic treatment for neurogenic bladder (catheterization, muscarinic antagonists), spasticity (baclofen, GABA b receptor agonists), pain (opioids)

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Acute inflammatory demyelinating polyradiculopathy

Most common subtype of Guillain-Barre Syndrome

Autoimmune condition that destroys Schwann Cells causing inflammation and demyelination of peripheral nerves and motor fibers. Results in symmetric ascending muscle weakness/paralysis beginning in lower extremities

Facial paralysis in 50% of cases. May see autonomic dysregulation (cardiac irregularities, HTN, hypotension) or sensory abnormalities. Almost all patients survive; the majority recover completely after weeks to months

Findings: High CSF protein with normal cell count (albuminocytologic dissociation). Increased protein may cause papilledema

Associated with infections (Campylobacter jejuni, viral) causing autoimmune attack of peripheral myelin due to molecular mimicry, inoculations, and stress, but no definitive link to pathogens

Respiratory support is critical until recovery. Additional treatment: plasmapharesis, IV immunoglobulins

180

Acute disseminated (postinfectious) encephalomyelitis

Multifocal periventricular inflammation and demyelination after infection (commonly measles or VZV) or certain vaccinations (rabies, smallpox)

181

Charcot-Marie-Tooth Disease

Also known as hereditary motor and sensory neuropathy (HMSN)

Group of progressive hereditary nerve disorders related to the defective production of protein involved in the structure and function of peripheral nerves or the myelin sheath.

Typically autosomal dominant inheritance pattern and associated with scoliosis and foot deformities (high or flat arches)

182

Krabbe Disease

Autosomal recessive lysosomal storage disease due to deficiency of galactocerebrosidase

Buildup of galactocerebroside and psychosine destroys myelin sheath.

Findings = peripheral neuropathy, developmental delay, optic atrophy, globoid cells

183

Metachromatic Leukodystrophy

Autosomal recessive lysosomal storage disease, most commonly due to arylsulfatase A deficiency

Buildup of sulfatides leads to impaired production and destruction of myelin sheath.

Findings = central and peripheral demyelination with ataxia, dementia

184

Progressive multifocal leukoencephalopathy

Demyelination of CNS due to destruction of oligodendrocytes. Associated with JC Virus.

Seen in 2-4% of AIDS patients (reactivation of latent viral infection). Rapidly progressive, usually fatal.

Increased risk associated with natalizumab, rituximab

185

Adrenoleukodystrophy

X-linked genetic disorder typically affecting males

Disrupts metabolism of very long chain fatty acids leading to excessive buildup in nervous system, adrenal glands, testes.

Progressive disease that can lead to long term coma/death and adrenal gland crisis

186

Partial (focal) seizures

Affect single area of the brain. Most commonly originate in medial temporal lobe. Often preceded by seizure aura; can secondarily generalize:

1) Simple partial (consciousness intact) - motor, sensory, autonomic, psychic

2) Complex partial (impaired consciousness)

187

Generalized seizures

Diffuse.

1) Absence (petit mal) - 3 Hx, no postictal confusion, blank stare

2) Myoclonic - quick, repetitive jerks

3) Tonic-clonic (grand mal) - alternating stiffening and movement

4) Tonic - stiffening

5) Atonic - "drop" seizures (falls to floor); commonly mistaken for fainting

188

Epilepsy

Disorder of recurrent seizures (febrile seizures are not epilepsy)

189

Status epilepticus

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

190

Causes of seizures by age

Children - genetic, infection (febrile), trauma, congenital, metabolic

Adults - tumor, trauma, stroke, infection

Elderly - stroke, tumor, trauma, metabolic, infection

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Differentiating headaches

Pain due to irritation of structures like the dura, cranial nerves or extracranial structures

1) Cluster HA
Unilateral
15min - 3hr, repetitive
Repetitive brief HAs. Excruciating periorbital pain with lacrimation and rhinorrhea. May induce Horner Syndrome. More common in males

Tx = 100% O2, sumatriptan

2) Tension HA
Bilateral
> 30mins (typically 4-6 hrs); constant
Steady pain. No photophobia or phonophobia. No aura.

Tx = analgesics, NSAIDs, acetaminophen; amitriptyline for chronic pain

3) Migraine
Unilateral
4-72hrs
Pulsating pain with nausea, photophobia, or phonophobia. May have "aura." Due to irritation of CN 5, meninges, or blood vessels (release of substance P, calcitonin gene-related peptide, vasoactive peptides)

Tx = Abortive therapies (triptans, NSAIDs) and prophylaxis (propranolol, topiramate, Ca channel blockers, amitriptyline)

POUND = Pulsatile, One-day duration, Unilateral, Nausea, Disabling

192

Vertigo

Sensation of spinning while actually stationary. Subtype of "dizziness," but distinct from "lightheadedness"

1) Peripheral vertigo - more common. Inner ear etiology (semicircular canal debris, vestibular nerve infection, Meniere disease). Positional testing leads to delayed horizontal nystagmus

2) Central vertigo - brain stem or cerebellar lesion (stroke affecting vestibular nuclei or posterior fossa tumor). Findings = directional change of nystagmus, skew deviation, diplopia, dysmetria. Positional testing yields immediate nystagmus in any direction; may change directions. Focal neurologic findings

193

Sturge-Weber Syndrome

A neurocutaneous disorder

Congenital, non-inherited (somatic), developmental anomaly of neural crest derivatives (mesoderm/ectoderm) due to activating mutation of GNAQ gene.

Affects small (capillary-sized) blood vessels leading to port wine stain of the face (nevus flammeus, a non-neoplastic "birthmark" in CN V1/V2 distribution); ipsilateral leptomeningeal angioma leading to seizures/epilepsy; intellectual disability; and episcleral hemangioma causing increased IOP leading to earl-onset glaucoma

STURGE = Sporadic, port wine Stain; Tram track calcifications (opposing gyri); Unilateral; Retardation (intellectual disability): Glaucoma, GNAQ gene; Epilepsy

194

Tuberous sclerosis

A neurocutaneous disorder

HAMARTOMAS

H = Hamartomas in CNS and skin
A = Angiofibromas
M = Mitral regurgitation
A = Ash-leaf spots
R = cardiac Rhabdomyoma
T = tuberous sclerosis
O = autosomal dOminant
M = Mental retardation
A = renal Angiomyolipoma
S = Seizures, Shagreen patches

Increased incidence of subependymal astrocytomas and ungual fibromas

195

Neurofibromatosis type 1 (von Recklinghausen disease)

A neurocutaneous disorder

Cafe-au-lait spots, Lisch nodules (pigmented iris hamartomas), cutaneous neurofibromas, optic gliomas, pheochromocytomas.

Mutated NF1 tumor suppressor gene (neurofibromin, a negative regulator of RAS) on chromosome 17. Skin tumors of NF1 are derived from neural crest cells

196

Von Hippel-Lindau disease

Hemangioblastomas (high vascularity with hyperchromatic nuclei) in retina, brain stem, cerebellum, spine; angiomatosis (cavernous hemangiomas in skin, mucosa, organs); bilateral renal cell carcinoma; pheochromocytomas.

197

List the adult primary brain tumors

1) Gliobastoma multiforme
2) Meningioma
3) Hemangioblastoma
4) Schwannoma
5) Oligodendroglioma
6) Pituitary adenoma

198

Glioblastoma multiforme

Adult

Common, highly malignant primary brain tumor with about 1 year median survival

Found in cerebral hemispheres. Can cross corpus callosum ("butterfly glioma")

Stain astrocytes for GFAP

Histology = pseudopalisading pleomorphic tumor cells - border central areas of necrosis and hemorrhage

199

Meningioma

Adult

Common, typically benign primary brain tumor. Most often occurs in convexities of hemispheres (near surfaces of brain) and parasagital region. Arises from arachnoid cells, is extra-axial (external to brain parenchyma), and may have a dural attachment ("tail").

Often asymptomatic; may present with seizures or focal neuro signs. Resection and/or radiosurgery

Histo = Spindle cells concentrically arranged in a whorled pattern; psammoma bodies (laminated calcifications)

200

hemangioblastoma

Adult

Most often cerebellar. Associated with von Hippel-Lindau syndrome when found with retinal angiomas. Can produce erythropoietin leading to secondary polycythemia

Histo = Closely arranged, thin-walled capillaries with minimal intervening parenchyma

201

Schwannoma

Adult

classically at the cerebellopontine angle, but can be along any peripheral nerve

schwann cell origin

S-100 (+)

Often localized to CN 8 leading to vestibular schwannoma. Resectable or treated with stereotactic radiosurgery

Bilateral vestibular schwannomas found in NF-2

202

Oligodendroglioma

Adult

Relatively rare, slow growing. Most often in frontal lobes. "Chicken wire" capillary pattern.

Histo = oligodendrocytes = "fried egg" cells - round nuclei with clear cytoplasm. Often calcified in oligodendroglioma

203

Pituitary adenoma - tumor qualities

Most commonly prolactinoma. Bitemporal hemianopia (shows normal visual field above, patient's perspective below) due to pressure on optic chiasm

Hyper or hypopituitarism are sequelae

204

List the childhood primary brain tumors

1) Pliocytic astrocytoma
2) Medulloblastoma
3) Ependymoma
4) Craniopharyngioma

205

Pliocytic (low grade) astrocytoma

Childhood

Usually well-circumscribed. In children, most often found in posterior fossa (cerebellum)

May be supratentorial.

GFAP +

Benign, good prognosis

Rosenthal fibers - eosinophils, corkscrew fibers

Cystic + solid (gross)

206

Medulloblastoma

Childhood

Highly malignant cerebellar tumor. A form of primitive neuroectodermal tumor. Can compress 4th ventricle, causing hydrocephalus. Can send "drop metastases" to spinal cord

Homer-Wright rosettes. Solid (gross), small blue cells (histo)

207

Ependyoma

Childhood

Ependymal cell tumors most commonly found in 4th ventricle. Can cause hydrocephalus. Poor prognosis

Characteristic perivascular rosettes. Rod-shaped blepharoplasts (basal ciliary bodies) found near nucleus

208

Craniopharyngioma

childhood

Benign childhood tumor, may be confused with pituitary adenoma (both can cause bitemporal hemianopia).

Most common childhood supratentorial tumor

Derived from remnants of Rathke pouch

Calcification is common (tooth enamel-like)

209

Herniation syndromes

1) Cingulate (subfalcine) herniation under falx cerebri - can compress ACA

2) Downward transtentorial (central) herniation - Caudal displacement of brain stem leads to rupture of paramedian basilar artery branches causing Duret hemorrhages

Usually fatal

3) Uncal herniation - Uncus = medial temoral lobe. Compresses ipsilateral CN 3 (blown pupil, "down and out" gaze), ipsilateral PCA (contralateral homonymous hemianopia), contralateral crus cerebri at the Kernohan notch (ipsilateral paresis; a "false localization" sign)

4) Cerebellar tonsillar herniation into the foramen magnum - coma and death result when these herniations compress the brain stem