Week 1 - Neuro

Question 1

Reaction of neurons to injury

Answer 1

eosinophilic change (ischemia/hypoxia)- LETHAL, takes 12hr to see, cell shrinks and loss of nissl
central chromatolysis (axonal damage)- switch from synaptic to structural protein, cell swelling and margination of nissl
inclusion formation
Lipofuscin accumulation (normal aging)

Question 2

Glial cells in CNS

Answer 2

neuroectoderm
Astrocytes: normally invisible, star shaped, GFAP, BBB, scars
Oligodendrocytes: myelination
Ependymal: cuboidal or columnar ciliated cells line ventricles, CSF-brain barrier
also Microglia- macrophage-derived cells

Question 3

CT vs MRI

Answer 3

CT: radiation, fast, available, cheaper, iodinated contrast
MRI: magnet, multiplanar, gadolinium contrast, slower, expensive
CT: better for trauma, bone, acute hemorrhage
MRI: better for soft tissue and contrast

Question 4

Acute intracranial hemorrhage

Answer 4

acute is bright on CT, chronic is dark
can be subarachnoid, subdural, epidural, parenchymal, or intraventricular
causes of subarachnoid= trauma and ruptured aneurysm

Question 5

Acute infarct

Answer 5

may not be seen on CT acutely (will only see if hemorrhage)

if high suspicion, get MRI (DWI field)

Question 6

Spine trauma

Answer 6

CT is initial screening exam

MRI is used for soft tissue

Question 7

Cerebral edema

Answer 7

vasogenic: extracellular, from increased permeability of BBB, mostly white matter, caused by tumors, abscesses, contusions, hematomas,, often responds to steroids or anti-VEGF
cytotoxic: intracellular, secondary to cell energy failure, gray matter, caused by ischemia/infarct, meningitis, trauma, siezures, encephalopathy

Question 8

Herniation in the CNS

Answer 8

due to increased intracranial pressure
Subfalcine: cingulate gyrus herniates under falx due to asymmetric swelling
Transtentorial: uncus (medial temporal) herniates through tentorial opening due to asymmetrical
Duret hemorrhage: fatal brainstem hemorrhage secondary to uncal herniation and tearing of vessels
Cerebellar tonsillar: caused by symmetric expansion, through foramen magnum

Question 9

Hydrocephalus

Answer 9

increase in CSF volume
communicating: non-obstructive, due to decreased absorption at arachnoid granulations
Non-communicating: obstruction in ventricle system, from tumor, congenital, thick meninges

Question 10

Skull fractures

Answer 10

linear, comminuted, or depressed
convexity or base
open or closed

Question 11

Concussion

Answer 11

parenchymal damage caused by trauma
biochemical and physiologic abnormalities, but no structural problems
constellation of immediate sx

Question 12

Contusion

Answer 12

parenchymal damage caused by trauma
superficial bruises of the brain
usually at crests of gyri, over orbital and temporal regions
small vessels, neurons, and glia are damaged
acute= wedge-shaped
old= brown/orange, macrophages with hemosiderin, astrocyte scar
Coup vs contrecoup

Question 13

Diffuse Axonal Injury (DAI)

Answer 13

acceleration injury (MVA)
loss of consciousness at onset without lucid interval
widespread damage to axons,, tends to be around corpus callosum and cerebellar peduncle
need microscopic evidence for diagnosis
acute= axonal swelling, B-amyloid, silver stain
subacute= microglia and swelling
chronic= degeneration

Question 14

Epidural, subdural, subarachnoid hematomas

Answer 14

Epidural= lens-shaped, middle meningeal artery, lucid interval, slow accumulation
Subdural= crescent-shaped, tear of bridging veins, more in elderly
Subarachnoid= from contusions, skull base fractures, blood from ventricles

Question 15

Sequelae of brain trauma

Answer 15

hydrocephalus
epilepsy
traumatic encephalopathy

Question 16

Brain death definition

Answer 16

unresponsive to pain
absence of reflexes
absence of respirations (pCO2 over 60)
temp under 32C 90F
SBP under 90
no sedatives or drugs on board

Question 17

Global ischemic injury

Answer 17

low systolic pressure under 50mm
damage mostly in watershed/border zones
if severe, can have widespread neuronal death
Most vulnerable regions to ischemia= hippocampus (CA1), cerebral cortex (laminar necrosis), purkinje cells or cerebellum,, determined by glutamate receptor density

Question 18

Focal ischemic injury

Answer 18

usually from a stroke (thrombosis, emboli)
most common sites= carotid bifurcation, origin of MCA, origin or end of basilar
Emboli are more likely hemorrhagic than athersclerosis
Lacunar infarcts= hyaline arterolosclerosis caused by HTN or DM, small strokes, usually subcortical

Question 19

Morphology of infarcts

Answer 19

gross:
acute= soft, swollen
subacute= liquefactive necrosis
chronic= cavitated
Microscopic:
acute= red neurons, pallor, maybe neutrophils
subacute= macrophages, necrotic tissue, reactive astrocytes
chronic= glial scar

Question 20

Cerebral venous thrombosis

Answer 20

causes hemorrhagic infarcts (usually parasagittal)

causes: infxn, injury, neoplasm, pregnancy, OCP, hematologic abn

Question 21

Intracerebral hemorrhage

Answer 21

most common cause= HTN, abrupt onset, usually in putamen, thalamus, pons, cerebellum
also vascular malformations (arteriovenous malformation or cavernous angioma) and amyloid angiopathy

Question 22

Subarachnoid hemorrhage

Answer 22

aneurisms: saccular (berry)= worst headache ever had

defect in media is congenital, usually at anterior circ branch points

Question 23

Cerebrovascular disease: pump

Answer 23

cardioembolism, MCA most common site
no flow= cortical laminar necrosis
low flow= watershed injury

Question 24

Cerebrovascular disease: pipes

Answer 24

large vessel: carotid plaques, stenosis,, really emboli is the problem (restricted to artery involved)
small vessel: lipohyalinosis (hyaline arterolosclerosis), in-situ thrombosis (Lacunar strokes), vessel rupture (intracerebral hemorrhage),, also aneurisms or arteriovenous malformations

Question 25

Cerebrovascular disease: passengers

Answer 25

``` blood disorders (rare) large vessel more than small (hypercoag states) ```

Question 26

Excitotoxicity cycle model

Answer 26

mitochondrial damage- ROS- activation of NMDA receptors- excess intracellular Ca- ATP depletion- cell death- excessive glutamate- more NMDA(cycle)

Question 27

Alzheimer's Disease (AD)

Answer 27

most common form of dementia progressive decline of cognitive fxn, esp recent memory and one more: language, abstract thinking, visuo-spatial, praxis, executive fxn Diagnostic criteria (DAT): dementia, 2 areas of cog impairment, normal sensorium, age 40-90, no other diseases Stage 1: new memory defect, topographic disorientation, anomia, depression Stage 2: recent and remote recall impaired, acalculia, delusions Stage 3: severely imapired intellect, sphincter control lost, limb rigidity and flexion posture Path: atrophy of gyri and wide sulci, increased ventricles (hydrocephalus ex vacuo),, extracellular deposition of AB, neuritic plaques (phosphorylated tau),, amyloid angiopathy is assoc with lobar hemorrhage 75% sporadic, 5% with fam hx auto dom (PSEN1, APP), APOE e4 dose is risk factor APP: normall cleaved with alpha and gamma secretase, pathologically cleaved with beta and gamma secretase

Question 28

Drugs for Alzheimers

Answer 28

(central) cholinesterase inhibitors: Donepezil, Rivastigmine, Galantamine modest improvements, GI sides, abnormal dreams NMDA channel blocker: Memantine, slows ds progression

Question 29

Frontotemporal Degeneration (FTD)

Answer 29

pathologic= frontotemporal lobar degeneration (FTLD) 50% sporadic, can be auto dom familial Behavioral variant: bi-frontal lobe atrophy, socially inappropriate behavior, apathy Primary progressive aphasia: -Progressive nonfluent aphasia: left peri-sylvian atrophy (fluency,Broca) -Semantic variant: bilateral anterior temporal lobe atrophy (comprehension,wernicke) Path: atrophy, Tauopathies (Pick's disease-Pick bodies), TDP-43 accumulation

Question 30

Parkinsonism

Answer 30

rigidity, bradykinesia, resting tremor | usually from Parkinson's disease, but can be other things too

Question 31

Parkinson's Disease (PD)

Answer 31

slight male predominance, 55-65yo, fam hx in 10% (Parkin gene, a-synuclein),, also assoc with environmental toxins resting asymmetric pill-rolling or chin tremor, bradykinesia, rigidity, gait disturbance, REM behavior disorder, olfactory loss, dysautonomia responds well to L-DOPA Path: pallor of substantia nigra, Lewy bodies (eosinophilic a-synuclein)

Question 32

Dementia with Lewy Body (DLB)

Answer 32

dementia + 2/3: fluctuating cognition, visual hallucinations(pleasant), parkinsonian motor signs neuroleptic sensitivity, low dopamine uptake

Question 33

Extrapyramidal system

Answer 33

cerebral cortex-- substantia nigra pc --dopamine-- striata-- -- -/- substantia nigra pr / globus pallidus i -/- -/- GPe -/- subthalamic nucleus -- SNpr/GPi SNpr/GPi -/- Thalamus -- cortex

Question 34

Parkinson's effect on extrapyramidal system

Answer 34

loss of dopamine from SNpc to Str thus loss of direct inhibition AND loss of inhibition of excitation of SNpr/GPi thus strong inhibition of thalamus and thus less excitation of cortex thus less motion

Question 35

Parkinson's Drugs

Answer 35

Levodopa (L-DOPA): decarboxylated to dopamine by L-AAAD in neurons. has systemic sides, short half-life, wears off after a few years,, sides= dyskinesia, confusion, GI, hypotension,, contra in glaucoma, psychosis, arrythmias, melanoma Carbidopa: co-admin with levodopa to inhibit L-AAAD not across BBB Entacapone: co-admin with levodopa as a COMT inhibitor (inhibits breakdown of dopamine) Dopamine receptor agonists: mimic dopamine without less oxidative stress and longer half-life and selectivity,, sides=nausea, more confusion, less dyskinesia -Pramipexole and ropinerole (D2) -Apomorphine (D4+, used only for last-ditch immediate therapy) MAO inhibitors (MAO-B selective for brain):stop dopamine breakdown, also reduces ROS,, modest benefit, well tolerated, anxiety and insomnia, serotonin syndrome -Selegiline, Rasagiline COMT inhibitors: stop breakdown of dopamine -Tolcapone(hepatotoxicity), Entacapone(co-admin with L-dopa to limit peripheral sides Antimuscarinics: used bc dopamine usually inhibits cholinergic neurons in striatum, modest effect, third choice, used in combo -trihexyphenidyl, Benztropine Amantadine: increases dopamine release, less effective, given with L-dopa

Question 36

Huntington Disease

Answer 36

autosomal dominant, CAG trinucleotide repeat, anticipation, toxic gain of fxn intranuclear inclusions in basal ganglia, loss of striatal neurons in caudate and putamen, and in cerebral cortex motor(chorea), cognitive, neuropsychiatric Loss of inhibition to the LGP thus more inhibition of STN, thus loss of stimulation of SNpr/GPi, thus less inhibition of thalamus and more stimulation of cortex Tx: Tetrabenzine (VMAT inhibitor), tx sx

Question 37

Amyotrophic lateral sclerosis (ALS)

Answer 37

males more, age around 60yo, mostly sporadic, 10% familial widespread degeneration of upper and lower motor neurons muscle atrophy, fasciculations due to loss of anterior horn/root cells spastic tone and hyperreflexia from loss of lateral corticospinal tracts mean survival= 3-5 yrs familial= auto dom, SOD1 mutation or TDP-43 accumulation Tx: Riluzole- NMDA inhibitor, modest effect

Question 38

Primary vs secondary headache

Answer 38

Primary: idiopathic, diagnosis of exclusion, no pathology (Migraine, cluster, or tension) Secondary: pathologic (traumatic, vascular, infxn, metabolic, tumor)

Question 39

Cluster headache

Answer 39

relatively rare at least 5 attacks that are frequent (assoc with solstices), severe, unilateral, supraorbital or temporal, last 15-180min also may have lacrimation, rhinorrhea, nasal swelling, miosis, ptosis, horner's

Question 40

Migraine headache

Answer 40

at least 5 attacks, last 4-74hrs, unilateral, pulsating, severe to moderate, aggravated by physical activity may have nausea, vomiting, photophobia mechanisms: cortical neuron hyperexcitability, cortical spreading depression (aura), abnormal peri-aqueductal grey brainstem fxn, activation of TGVS (trigeminovascular system)

Question 41

Tension headache

Answer 41

occurs 15d/month for 3mo, lasts hours or continuous, pressing/tightening, mild or moderate, bilateral usually does not have photophobia or nausea causes: stress, neck pain

Question 42

Serotonin

Answer 42

synthesis: from tryptophan, tryptophan hydroxylase is rate limiting (needs O2 and pteridine) Metabolism: by MAO, neural action stopped by SERT,, converted to melatonin in pineal gland in CNS, serotonin cell bodies are in midbrain raphe nucleus and project everywhere Receptors: 13 subtypes, mostly G-coupled 5-HT1=inhibit adenylate cyclase, 2=PI hydrolysis, 3=cation channel, 4-7= activate adenylate cyclase also have autoreceptors to decrease release

Question 43

Serotonin CNS pharmacology

Answer 43

agonists: -Lysergic acid diethylamide (LSD): 5-HT2, hallucinogen Buspirone: 5-HT1a, anti-anxiety Sumatriptan: 5-HT1b,d on blood vessels, tx of migraine headache, stops existing headaches

Question 44

Triptans

Answer 44

migraine abortive agents e.g. sumatriptan 5-HT1b,d agonists inhibit vasoactive peptide release, promote vasoconstriction blocks brainstem pain pathways, inhibits trigeminal nerve sides: nausea, vasoconstriction, angina, flushing contraind: stroke, MI, HTN

Question 45

Other migraine abortive agents

Answer 45

Ergots (DHE) - ergotamine NSAIDS + caffeine steroids

Question 46

Migraine prophylactic drugs

Answer 46

``` Tricyclic antidepressants (Amitryptyline, Nortriptyline), sedating, anticholinergic, effective Antiseizure agents: valproic acid, topiramate Vasoactive agents: B-blockers, Ca-channel blockers, variable efficacy ```

Question 47

Astrocytomas

Answer 47

most common glial tumor 80% are glioblastomas sx: seizures, focal deficits (gradual), headaches diffuse astrocytomas have tendency to become anaplastic over time Pilocytic astrocytoma: most common in kids, usually in cerebellum, well demarcated with adjacent cyst, slow growing, excellent prognosis Diffuse Astrocytoma (35yo) Anaplastic astrocytoma (45yo) Gliooblastoma multiforme (61yo)- necrosis with pseudopallisading, vascular proliferation

Question 48

Oligodendroglioma

Answer 48

50-60yo long hx of progressive neuro sx well-defined hypodense mass, maybe with calcification, fried egg cells prognosis better than astrocytomas Good prognostic: allelic loss of chromosome 1p and 19q

Question 49

Ependymoma

Answer 49

kids and young adults along ventricular system, usually 4th ventricle sx: hydrocephalus, seizures well-circumscribed mass prognosis: 4yrs true rosettes, columnar cells around central lumen

Question 50

Choroid plexus papilloma

Answer 50

``` usually less than 20yo usually in the ventricles presents with hydrocephalus well-demarcated, cauliflower-like mass -good prognosis can also get choroid plexus carcinoma (usually kids, not adults)- bad prognosis ```

Question 51

Colloid cyst

Answer 51

usually on roof of third ventricle positional obstruction of foramen of monroe thus positional headache thin walled cyst lined by epithelium

Question 52

Ganglioglioma

Answer 52

``` usually 0-30yo contains neurons and astrocytes long standing hx of seizures usually supratentorial in temporal lobe solid or cystic, calcification looks similar to pilocytic astrocytoma with cyst and adjacent mass -surgery is curative ```

Question 53

Medulloblastoma

Answer 53

primitive neuroectoderm neoplasm of posterior fossa most in less than 10yo sx: cerebellar dysfxn, increased intracranial pressure well-defined contrast-enhancing mass good prognosis with surgery and radiation can form drop metastasis through subarachnoid space homer wright rosettes, synaptophysin

Question 54

Primary CNS Lymphoma

Answer 54

``` 40-60yo, younger end if immunocompromised assoc with EBV mostly B-cell, usually supratentorial some spread through meninges bad prognosis ```

Question 55

Meningioma

Answer 55

most common extraparenchymal neoplasm of CNS middle to late adults, more women sx due to mass effect dural-based, vascular, contrast-enhancing, well-defined assoc with radiation, NF2 sheets of cells with indistinct borders, whorls and psammomma bodies

Question 56

Schwannomas

Answer 56

benign tumor of schwann cells 40-60yo peripheral nerves, usually head and neck asymptomatic masses, can cause radicular pain if along spinal cord Antoni A and B tissue Intracranial= 8th nerve= hearing loss, tinnitis, assoc with neurofibromatosis type 2

Question 57

Neurofibroma

Answer 57

benign tumor with schwann cells, fibroblasts, and perineural cells assoc with neurofibromatosis type 1 can be cutaneous (common, solitary) or peripheral nerve (NF1) Plexiform neurofibroma: always NF1, tends to affect large nerves and plexus, high likelyhood of malignant

Question 58

Malignant peripheral nerve sheath tumor

Answer 58

mostly in extremities, otften trigeminal nerve assoc with NF1 high grade and aggressive infiltrative, fleshy masses, highly cellular

Question 59

Neurofibromatosis 1

Answer 59

von Recklinghausen disease autosomal dominant neurofibromas, cafe-au-lait spots, Lisch nodules(hamartomas in iris), optic glioma, osseous lesions, axillary freckling, fam hx NF1 gene on chr17, neurofibromin

Question 60

Neurofibromatosis 2

Answer 60

autosomal dominant gene on chr22, merlin bilateral vestibular schwannomas, fam hx, meningiomas, schwannomas, gliomas, neurofibromas lens opacity, cerebral calcifications

Question 61

Von Hippl Lindau disease

Answer 61

auto dom VHL gene on chr3 hemangioblastomas of CNS and retina, renal cell carcinoma, pheochromocytoma, visceral cysts

Question 62

Hemangioblastoma

Answer 62

usually in cerebellum sx related to increased pressure well-defined enhancing cystic mass with mural nodule numerous vessels with stromal cells with foamy cytoplasm (fat) tx= surgery

Question 63

Tuberous sclerosis

Answer 63

``` auto dom, fam hx in 50% genes: TSC1=hamartin, TSC2=tuberin cortical hamartomas (tubers), glioneural hamartomas, subependymal giant cell astrocytomas, other ```

Question 64

Paraneoplastic syndromes

Answer 64

subacute cerebellar ataxia: assoc with ovarian and breast cancer, antibody to purkinje cells Eaton Myasthenic syndrome: muscle weakness esp in legs, antibodies to PQ type v-gated Ca-channels, assoc with SCLC