How can we help?

You can also find more resources in our Help Center.

MLK USMLE - Step1: Neuro

STUDY
PLAY
microglia
mesoderm derived, HIV infected --> multinucleated giant cells
oligodendrocytes
target of MS, fried eggs
schwann cells
neural crest, target of Guillain Barre, acoustic schwannoma tumor
spindle shaped, S100+ (neural crest derived)
free nerve endings
pain + temp; C - slow unmyelinated; Adelta - fast myelinated
meissners corpuscles
fast adaptation and fine touch for hairless skin; Abeta large myelinated fibers
pacinian corpuscles
vibration + pressure; Abeta large myelinated fibers, deep
merkel's disks
slow adapatation and static touch for hair follicles; Abeta large myelinated fibers
endoneurium, perineurium, epineurium
guillame-barre in endoneurium
NTs - location and dz
NE: pons locus ceruleus, high anxiety, low depression
DA: midbrain VTA + SNc, high schizophrenia, low PD
5HT: reticular formation raphae nucleus, low anxiety and depression
AcCh: basal forebrain nucleus of meynert/nucleus basalis, low Alz + Huntingtons, high in REM sleep
GABA: NAcc ventral striatum, low anxiety
BBB
endothelial tight junctions, BM, astrocyte foot processes
size and lipid solubility determine permeability

fenestrated capillaries:
area postrema in medulla - vomiting
aka chemoreceptor trigger zone, dorsal
surface of the medulla
OVLT periventricular - ADH monitor

underdeveloped in infant, susceptible to CNS penetration -
ex: hyperbili in baby causes CNS lethargy, spasms...not in adult
ex: drugs

angiogenesis in brain tumors does not make tight junctions, disordered, therefore disrupts BBB
--> CONTRAST MRI detects
--> also systemic chemo can penetrate these areas for tx
hypothalamus
lateral - hunger, anorexia, failure to thrive
medial - satiety, hyperphagia

anterior - cooling, parasympathetic
posterior - heating, sympathetic

suprachiasmatic - circadian

PP:
supraoptic - ADH
paraventricular - oxytocin
thalamus
relays all sensory except olfaction

VPL - DCMLS
VPM - trigeminal
LGN - vision, superior colliculus
MGN - hearing, inferior collicuolus, superior olive

VA/VL - motor inputs/outputs (BG, SNc, GP, motorCTX)

VPL/VPM/LGN/MGN - sensory inputs/outputs

AN - limbic

MD - PFC/limbic/higher order
lesion = memory loss = wernicke-korsakoff

pulvinar - integrates inputs from all over thalamus and CTX --> lesion = sensory dysphasia
limbic system
cingulate, hippocampus, fornix, mamillary bodies, septal n.,

Papez circuit: amygdala --> mamillary --> ant. thalamus
cerebellum
(all ipsilateral) DCMLS SC, inferior olive --> inferior cerebellar peduncle --> climbing/mossy fibers

(all contralateral) cortical inputs --> middle cerebellar peduncle --> mossy fibers

(all contralateral) cerebellar outputs to CTX, SC = purkinje --> deep nuclei --> superior cerebellar peduncle

lateral ctx - lateral limbs, voluntary movement, to cerebral CTX
medial ctx - coordination/balance, ipsilateral SC inputs

vermis - trunk
lateral ctx - lateral limbs
flocconodular lobe - vestibular nuclei
dentate n. - contralateral CTX
E+G n. = contralateral SC
olivary n
superior = auditory
inferior = movement via inferior cerebellar peduncle
basal ganglia
voluntary movements, posture

striatum = putamen + caudate
lentiform = putamen + globus pallidus
subthalamic n
substantia nigra

direct path: ctx-striatium-GPi-thalamus-ctx
excitatory, SNc-->(+)D1-R striatum-->increase motion

indirect path: ctx-striatum-GP2e-STN-GPi-thalamus
inhibitory, SNc-->(-)D2-R striatum-->increase motion

PD - SNc
Huntingtons - striatum
hemiballismus - STN
PD
Lewy bodies = alpha synuclein
TRAP: tremor, pill roll, akinesia, unstable posture, slooooow
shuffling gait, masked facies, dementia

DA neuron loss in substantia nigra, decr DA to BG

tx: carbidopa + levodopa, pramipexole/bromocriptine
entacopone/tolcapone
selegiline

note: atypical antipsychotics can be anti-DA, schizophrenia pts taking risperidone/clozapine, etc can look like PD. MPTP antiemetic also induces PD sx

s/e of DA tx:
NV - improved with carbidopa, pts can
develop tolerance to this
orthostatic hypotension, hot flashes -
improved by carbidopa
anxiety/agitation - CENTRAL EFFECT OF
DA TX, NO TOLERANCE DEVELOPED TO
THIS

on/off phenomenon with DA tx - DRUG RESPONSE IS UNPREDICTABLE
hemiballismus
contralateral STN, strokes, flailing
huntingtons
ANTICIPATION = CAG repeat in huntingtin, chr4
mutated huntingtin hypermethylates DNA
transcriptional repression
glutamate toxicity/NMDAR, loss of AcCh/GABA in caudate

chorea/agression/depression/dementia/athetosis
(writhing fingers)

atrophy of the striatum (caudate+putamen), loss of GABAergics and cholinergics

...other choreic dz: syndenham's chorea in rheumatic fever, tardive dyskinesia, Wilson's dz
myoclonus
jerks, hiccups
dystonia
sustained cramp
broca vs wernicke
broca - inferior frontal gyrus, motor/expression and agrammatical...associated with arm/face weakness (arm face motor ctx proximity)

wernicke - superior temporal gyrus, receptive, can't name, understanding, anosognosia (unaware of deficit)...associated with contralateral field deficits (optic radiation proximity)

global = broca+wernicke

connected by arcuate fasciculus, lesion = poor repetition
circle of willis
lesions:
generally: anterior circle - sensory/motor/aphasias; posterior circle - CNs/coma/cerebellar ataxia

vertebral a./anterior spinal: medial medullary syndrome, motor paralysis

PICA: lateral medullary syndrome, loss of sensations esp. pain/temp, Horners, loss of gag reflex

AICA: pons, ipsilateral facial paralysis, nystagmus, dystaxia

PCA: occipital, contralateral hemianopia, macular sparing

MCA: contralateral face/arm paralysis, verbal aphasias, left sided neglect

ACA: leg/feet paralysis

anterior communicating: Berry aneurysm, visual field defects

posterior communicating: occulomotor palsy

lateral striae (part of MCA): internal capsule, BG, motor hemiparesis

basilar a - pons/midbrain, locked in syndrome with eyes intact

subclavian steal - thrombosis of left subclavian proximal to vertebral a., retrograde flow down left vertebral to bypass clot --> weak left arm
aneurysms
berry aneurysms in circle of willis bifurcations
high risk: ADPKD, ehlers danlos, marfans, coarctation of the aorta

"worst headache ever", vomiting (sx of high ICP)
if Marfans on board, can hear mitral valve prolapse mid-systolic click
CSF with blood, high bili

charcot-bouchard microaneurysms - htn
intracranial hemorrhages
epidural hematoma - middle meningeal a. (from maxillary a) rupture, temporal bone frac, does not cross suture lines, herniations, will typically see LOC acutely after trauma --> LUCID INTERVAL of normal function recovers...then rapid decline


subdural hematoma - bridging vein rupture, typically from trauma, slow bleed, delayed ssx onset, crosses suture lines...think chronic
can see changes in personality, AMS after a week

subarachnoid hemorrhage - aneurysm rupture, high risk marfans/ehlers danlos/ADPKD/AVM, bloody or yellow spina tap, tx with Ca channel block

parenchymal hematoma - htn, amyloidosis, DM, tumor
ischemia in the brain
high risk in watershed, hippocampus, CTX, cerebellum

irreversible injury in 12-24 hrs
glial scar after 2wks

atherosclerosis - ischemic stroke, necrosis, cyst with gliosis

hemorrage - aneurysm rupture, ischemia/reperfusion

SAH - aneurysms, atherosclerosis, bacterial emboli in vessel wall=mycotic aneurysm
CAN CAUSE SECONDARY ARTERIAL VASOSPASM --> ISCHEMIA
--> days after SAH, will see new FOCAL
NEURO DEFICITS
--> TX: CA CHANNEL BLOCK -
NEMIDIPINE
worst ha ever, NV, photophobia, coma
hyperdense blood all over the place

spontaneous intraparenchymal - HTN typically

Charcot Bouchard aneurysms - chronic HTN, hits along vessel path, ESP BG

ischemic stroke - emboli/Afib/carotid dissection/endocarditis

lacunar stroke - deep penetrating arteries, typically from chronic HTN, MULTIPLE small cavity infarcts

TIA

imaging: BRIGHT on MRI; DARK on CT

tPA for clots, not bleeds
dural veinous sinuses
in dura mater between meningeal/periosteal layers
cerebral veins --> venous sinuses --> INTERNAL JUGLUAR

superior sagittal, inferior sagittal, cavernous, straight sinus, great vein of galen, confluence of sinuses, transverse-->sigmoid sinus --> jugular foramen --> jugular vein
ventricles
CSF from choroid plexus

lateral/ctx --> monro --> third/thalamus --> aqueduct --> fourth/mid-pon-medulla with lateral Luschkas and medial Magendies
hydrocephalus
normal pressure - expansion of ventricles because not absorbing CSF in villi, typically secondary to meningeal hemorrhage
wet, wobbly, wacky

communicating - decr CSF absorption in arachnoid villi typically from adhesions after meningitis, incr ICP, papilledema, herniation

obstructive - blockage/stenosis in ventricles (monroe, aqueduct)

hydrocephalus ex vacuo - incr CSF with normal ICP + with brain atrophy in advanced dz (huntingtons, alz, HIV, picks FTD

benign intracranial htn - incr resistance to CSF outflow at arachnoid villi, obese young women
papilledema without mass, incr CSF pressure, decr vision, slit like ventricles
spinal nerves
cervical nerves above bone, rest below bone

8:12:5:5:1

disk herniations
spinal tap
between L3-L5 cauda equina
SC tracts
lateral corticospinal tract - crosses at pyramidal decussation in caudal medulla

anterior corticospinal tract - crosses at spinal level

spinothalamic - crosses after lissaur two levels up, to VPL thalamus

DCMLS crosses in medulla before ML, to VPL thalamus

spinocerellar stays ipsilateral

note sympathetics only T1-L2
LMN + UMN lesions
UMN - incr gain/reflex/tone, weakness, babinski, spastic paralysis, clasp knife

LMN - decr gain/reflex/tone, with weakness, atrophy, fasciculations
SC lesions
anterior horn - poliomyelitis, Werdnig-Hoffman = flaccid paralysis

DCMLS/spinothalamic - MS = scanning speech/tremor/nystagmus

lateral CS tract + anterior horn - ALS = UMN/LMN ssx, Riluzole tx, SOD1, decr glutamate release

anterior spinal arteries - high risk in thoracic, can include lissaur tract with pernicioius anemia

DRG + DCMLS - tabes dorsalis teritary syphilis = ataxia

spinothalamic - syringomyelia (anterior white commissure)

DCMLS+spinocerebellar - B12 deficiency, Fredreichs ataxia

anterior horn - poliomyelitis, poliovirus, fecal oral, LMN ssx

LMN dz floppy baby - infantile SMA, AR
tabes dorsalis
tertiary syphilis, proprioception/ataxia, Argyll Robertson pupil (accomodates but does not react), loss of DTRs, Romberg
Friedreichs ataxia
AR, trinucleotide repeat, frataxin, gait, nystagmus, hammertoes/high arch, kyphoscoliosis

cause of death: hypertrophic cardiomyopathy

DCMLS, lateral CST, spinocerebellar tract

VITAMIN E DEFICIENCY MIMICS THIS
brown-sequard
SC hemisection
motor ssx: UMN ipsilateral, LMN at level
sensory ssx: ipsilateral DCMLS below + spinothalamic at level, contralateral spinothalamic below
Horners
loss of sympathetics
hypothalamus-intermediolateral SC T1-L2 -sympathetic chain to cervical ganglion on internal carotid/juguluar-third order neuron to end organ

ptosis, anhidrosis, miosis

SC lesion above T1 (superior cervical ganglion), pancoast tumor, brown sequard, brainstem lesions, neck trauma, carotid dissection
note pancoasts tumor can cause ulnar nerve pain
key dermatomes
T4 nipple
T10 umbilicus
L1 inguinal ligament
L4 kneecap
S2/3/4 penis sensation

referred pain from diaphragam + GB to shoulder via phrenic n.
reflex SC segments
S1/2 heel (S1)
L3/4 knee (L3)
C5/6 bicep (C5)
C7/8 tricep (C7)
primitive reflexes
suckle, rooting, palmar/plantar grasp, babinksi

adult - frontal lobe lesions
<1y/o - positive babinski is normal
brainstem
medial CN = motor = 3,6,12
trochlear is only dorsal exiting CN

superior colliculus = vision
inferior colliculus = hearing

parinaud syndrome = superior colliculus lesion, pinealoma --> paralysis of conjugate vertical gaze
also hydrocephalus
brainstem lesions
motor:
pons - locked in
medial medulla - medial medullary syndrome (contralateral UMN paralysis, ipsilateral tongue LMN paralysis)

sensory:
lateral medulla - lateral medullary/Wallenberg
PICA stroke
ipsilateral Horners, nystagmus, on side of the lesion, ipsilateral limb ataxia, vertigo, contralateral loss pain/temp on body, ipsilateral loss pain/temp on face, also LMN paralysis CN 5,9,10,11
CNs
SSMMBMBSBBMM
2:2:4:4
dorsolateral - sensory, alar plate
sulcus limitans
ventromedial - motor, basal plate

1 - olfactory, straight to CTX

2 - optic, sensory arm reflex pupil

3 - oculomotor, everything except SO + LR
motor arm reflex edinger-westphal for pupil constrict, parasymp
paralysis = unilateral ptosis, gaze palsy (down+out)..typically from berry aneurysm or uncal herniation compression, or ischemia (diabetes)

4 - trochlear, SO, down+in, crosses contralateral

5 - trigeminal, sense face, muscles mastication + tensor tympani/palatini
sensory arm reflexes: corneal (V1), lacrimation (V2), jaw jerk (V3)
motor arm reflex: jaw jerk
mesencephalic and principle nucleus. is sensory
motor nucleus. is motor

6 - abducens, LR, think MLF with MR in MS

7 - facial, expression muscles, ant 2/3 taste, stapedius
UMN = upper face gets bilateral, lower face gets contralateral
LMN = Bell's palsy - AIDS, lyme, HSV, Sarcoid, tumors, diabetes
motor arm reflex - corneal (temporal, orbicularis o), lacrimation

8 - vestibulocochlear

9 - glossopharyngeal, post 1/3 taste, swallow, carotid body/sinus baro/chemo-R, stylopharyngeus
sensory/motor arm reflex: gag
external ear sensation
parasymp: parotid gland (otic ganglion)

10 - vagus, epiglotis taste, swallow, midline uvula, talk/cough, aortic bar/chemo-R, thoracoabdominal viscera
motor arm reflex: gag
aneurysms can compress --> cough, hoarseness

11 - spinoaccesory, SCM/trap + larynx

12 - hypoglossal, tongue
vagus n. in medulla
n. Solitarius - all Sensory
n. aMbiguous - all Motor
dorsal motor n. - autonomics
CN pathways in skull
CN1: cribiform plate

CN2-6: middle cranial fossa (sphenoid)
optic canal - CN2
superior orbital fissure - CN3/4/5-1/6
foramen rotundum - CN5-2
foramen ovale - CN5-3

CN7-12: posterior cranial fossa (temporal/occipital)
internal auditory meatus - CN7/8
jugular foramen - CN9/10/11 + jugular v.
hypoglossal canal - CN12
foramen magnum - CN12
cavernous sinus
venous sinus, adjacent to pituitary, sphenoid bone inferior, blood from eye/CTX, drains into internal jugular v.

CN2-6 (incl V1/V2) pass through - if engorged = opthalmoplegia, opthalmic/maxilla sensory loss
CN 12, 5, 10, 11 lesions
CN12 - tongue pushes
CN5 - jaw pushes
CN10 - uvula pulls
CN11 - SCM pulls, trap droops

note all corticobulbar are UMN bilaterally innervated except lower face/CN7 = contralateral
CN5 muscles of mastication
close =
Masseter, teMporalis, Medial pterygoid

open =
Lateral pterygoid
eye and glaucoma
aqueous humor from ciliar body EPITHELIUM -->anterior chamber --> drains via canal of schlemm

glaucoma: incr IOP from aqueous humor, optic disk atrophy, CUPPING

typically affects PERIPHERAL vision, spares central
(unlike macular degeneration which hits central)

- angle = cornea/iris

- open/wide angle: canal of schlemm doesnt drain,
anterior chamber incr IOP, silent/painless
tx: pilocarpine/carbachol - cholinergic agonits,
contracts ciliary m, slack suspensory ligaments,
widen canal of Schlemm, incr drainage
pilocarpine - M3/M2 agonist

can also use Epi, non selective beta block (timolol) + acetazolamide (CA
inhib) to decr secretion from ciliary epithelium, and PG (incr outflow)

- closed/narrow angle: space between iris and cornea doesnt fill anterior chamber --> incr posterior chamber IOP, painful, blindness, rock hard eye, ha, EMERGENCY

can be precipitated by ATROPINE, this is sometimes given for brady/hypotensive MI
cataracts
painless, bilateral opacification of lens, decr vision
think: sorbitol/DM
papilledema
(normal eye image)

incr ICP, elevated optic disk w/ blurred margins

think hydrocephalus, cavernous sinus
EOMs
trochlear/SO - down and in
abducens/LR - laterally
pupil control
constriction/miosis:
pupillary sphincter, parasymp, CN3 edinger-westphal --> ciliary ganglion

dilation/mydriasis:
pupillary dilator, symp, T1-->superior cervical ganglion -->long ciliary nerve
pupil reflex
CN2 --> pretectal nuclei midbrain --> EW n. --> bilateral parasymp vai CN3 --> ciliary ganglion

oculomotor nerve outside is parasympathetic fibers - affected by compression (berry aneurysm, blown pupil)

oculomotor nerve inside is CN to EOM - affected by vascular dz (diabetes/glucose --> sorbitol)
retinal detachment
trauma, diabetes
macular degeneration (age related)
hits fovea/macula - loss of CENTRAL vision
(unlike glaucoma which hits peripheral)
macula - temporal to optic disk, fine detail vision
fovea - center of macula, highest density of cones
and least convergent inputs to bipolar cells

dry/slow = fat deposition (Drusen)
wet/rapid = neovascularization (metamorphosia)

assess with Amsler grid, will see grid distortion in the center
visual field defects
internuclear opthalmoplegia
MLF syndrome in MS
DENUDATION/demyelination OF AXONS in MLF
ipsilateral MR palsy, contralateral LR nystagmus
Alzheimer's dz
decr AcCh hippocampus + n. basalis
beta-amyloid plaques extracellular
tau tangles intracellular

early onset: APP, presnilin1/2
late onset: ApoE4
Picks FTD
dementia, aphasia, personality change
parietal lobe, superior temporal gyrus
tau tangles
Lewy body dementia
PD + dementia + hallucinations
alpha-synulein defect
creutzfeldt-jakob dz
prions, spongiform ctx w/ vaculoes, beta-sheets resistant to proteases

NO inflammation
MS
AI demyelination
scanning speech, intention tremor, nystagmus
initially ASYMMETRIC, disseminated:
optic neuritis (PAIN WITH EYE MOVEMENTS), MLF syndrome, hemiparesis, hemisensory sx, incontinence

IgG in CSF, oligoclonal, suggests Bcell**
(typically normal WBC, but can be elevated, nonspecific)

periventricular demyelinating plaques on MRI
oligodendrocyte apoptosis

tx: beta-IFN, immunosuppress

relapsing remitting, secondary progressive
guillain-barre
inflammatory demyelinating polyradiculopathy, symmetric ascending paralysis, autonomic dysfunction

associated with infections: campylobacter, HSV, CMV, EBV, mycoplasma pneumo

albumin-cytologic dissociation: high protein, without elevated cells

plasmapheresis, IV Ig, resp support
progressive multifocal leukoencephalopathy
demyelinating CNS, oligodendrocyte destruction

JC virus = papova family, latent in immunocompetent hosts, flares up with immunocompromised (HIV, lymphoma/leukemia), SLOW viral infection, progressive demyelination

progressive decline in mental function
acute disseminated post-infectious encephalomyelitis
multifocal perivenular inflammation/demyelination

Zoster, measles
metachomatic leukodystrophy
AR lysosomal storage dz, demyelinating
charcot-marie-tooth dz
hereditary motor/sensory neuropathy, myelin mutation

feet/ankles, high arch, claw toes
subacute combined degeneration of the cord
B12 deficiency, DCMLS + CST demyelination, axon degeneration

SYMMETRIC myelin layer vacuolization and axon degeneration

eg: CANT WALK (BILATERAL)
seizures
parital: 1 brain area (medial temporal), often aura
will get sx restricted to one area, not whole body

simple partial: consciousness intact with motor/sensory change

complex partial: impaired consciousness/aura/post ictal with motor/sensory change

generalized: multiple brain regions

absence (generalized): 3hz, no post-ictal sx

myoclonic (generalized): jerks

tonic (generalized): stiffening on/off

tonic/clonic (generalized)

atonic (generalized): drop seizures

epilepsy: recurrent

febrile seizure: NOT epilepsy

can be breathing deeply after seizure from uncoupling of breathing rhythm --> met acidosis

tx: incr GABA, open Cl channels, hyperpol
barbituates - incr duration of Cl channel opening
benzos - incr frequency of Cl channel opening
valproate: hepatotoxic, neutropenia,
thrombocyotpenia, teratogen
carbamazepine
hepatotoxic, aplastic anemia, agranulocytosis
phenytoin - gingival hypertrophy, teratogen
ethosuximide/lamotrigine - SJ syndrome (bullous erythema multiforme)
phenobarbital+carbamazipine - CYP450 inducer, drug interactions
primidone
headaches
migraine - unilateral, nausea, photophobia, phonophobia...irritation CN5, substanceP
can be associated with menstruation, higher in women, gradual onset with crescendo, pulsatile,
+/- aura
tx: betablock, NSAID, sumatriptan (5HT agonist) for acute, for chronic beta-blocker/verapamil, aceta/indomethacin

tension - bilateral >30mins, NO photphobia or aura, band-like tightness/pressure

cluster - ALWAYS unilateral, periorbital/temporal, lacrimation, runny nose, sweating, more in men, maybe Horners
tx: sumatriptan

SAH - worst headache ever
vertigo
peripheral - inner ear: menieres, semicircular canal, vestibular nerve infection

central - brain stem/cerebellum: tumor
sturge-weber syndrome
aka encephalotrigeminal angiomatosis

neurocutaneous, congenital, port-wine stain (typically in distribution of CNV branch), leptomeningeal angiomas, pheo's, glaucoma, heterochromia of the iris, visual field changes, seizures, hemiparesis
tuberous sclerosis
neurocutaneous, AD TSC1/2 tumor suppressor gene, typically location of denovo two hit determines distribution of ssx
CNS:
hamartomas, subependymal nodules, astrocytomas
cause seizures, MENTAL RETARDATION
retinal hamartoma
skin:
ash-leaf spots: elliptical HYPOpigmented macules
adenoma sebaceum: small angiofibromas typically
malar on face
shagreen patches: firm red raised leathery on back
heart:
cardiac rhabdomyosarcoma
renal:
angiomyolipomas, cysts
neurofibromatosis type 1
aka Von Recklinghausens

inherited PERIPHERAL nervous sx tumors
neural crest derived
neurocutaneous, neurofibromas, cafe au lait spots, Lisch nodules in iris, optic gliomas, pheo's

AD, NF-1, chr17
von hippel-lindau dz
neurocutaneous, AD, VHL tumor suppressor gene, chr 3

diffuse hemangiomas, cavernous hemangiomas in cerebellum/medulla/SC
bilateral retinal hemangioma
cysts and/or neoplasm anywhere - liver, epididymis, pancreas, renal
high risk renal clear cell/retinal carcinoma, pheo's

death by renal cell carcinoma in 40s - watch kidneys
adult brain tumors
typically primary
think progressive HA, weakness, chronic and non-palliating
typically supra tentorial


most common = glioblastoma multiforme
typically in subcortical white matter
astrocyte derived
bad prognosis, GFAP+ astrocytes, can cross corpus callosum, pseudopalisading - crosses corpus collosum, butterfly glioma along vetricles supra tentorial, GFAP positive
NECROSIS essential feature, microvascular proliferation comomon


next = meningioma
in hemispheres, parasagittal typically (leg weakness/spasticity), arachnoid cell orgin penetrating dura, psommoma bodies, spindle cells, benign, slow growing, can present asymptomatic, or hydrocephalus, seizures, etc


next = acoustic schwannoma
local to CN8, cerebellopontine angle, NF-2 associated
tinnitus and unilateral hearing loss
S100+ (neural crest derived)

pituitary adenoma: typically prolactinoma, bitemporal hemianopsia, Rathke's pouch

CNS lymphoma = typically Bcell derived, think AIDS

mets (MORE COMMON than primary CNS tumors):
Lots of Bad Stuff Kills Glia =
lung, breast, skin (melanoma), kidney (renal cell), GI
hematogenous spread - gray/white junctions and watershed areas
ha, siezures, stroke, NV, AMS, personality change,
aphasia, weakness, etc
child brain tumors
kids get tumors typically infra-tentorial

most common = pilocytic astrocytoma
cerebellum/brainstem/hypothalamus/ optic pathways, GFAP+, benign, Rosenthal fingers, spindle cells with hair-like glial processes associated with microcysts, granular eosinophilic bodies

medulloblastoma = malignant cerebellar tumor, hydrocephalus causing, +Rosettes
headaches, vomiting, fatigue, ataxia
primitive neuroectoderm tumor
small, poorly differentiated

ependymoma - hydrocephalus, typically 4th ventricle in kids, spinal in adults
process tapering toward blood vessels

hemangioblastoma - VHL sydrome associated, cerebellum, EPO producing --> polycythemia

craniopharyngioma - benign, supratentorial, Rathke's pouch ectoderm, CALCIFIC, cystic with solid areas, filled with yellow viscous fluid rich in CHOLESTEROL
ssx: ha, growth failure, bitemporal hemianopia

neuroblastomas - most common extracranial solid tumor in kids
undifferentiated, small, round, blue cells
neuropil is pathognomonic, neuron marker stain +
elevated homovanillic acid (HVA) or vanillylmandelic acid (VMA) in UA
N-MYC* chr2

Turcot's syndrome - association between colonic and brain tumors
AD familial adenomatous polyposis - high risk for
medulloblastoma and glioma
hereditary nonpolyposis colorectal carcinoma -
high risk for gliomas
brain germinoma
pineal gland tumor, precocious puberty, obstructive hydrocephalus, Parinaud syndrome (upward gaze paralysis + convergence)
brain herniations with supratentorial mass
- cingulate herniation under falx cerebri, ACA compression

- downward transtentorial herniation

- uncal herniation if in medial temporal lobe
mydriasis, ptosis: CN3 --> levator palpebrae
contralateral hemianopa: PCA compression
ipsilateral paresis: crus cerebri compression
duret hemorrhages: caudal displacement

- cerebellar tonsillar herniation into foramen magnum

if brain stem compressed - coma/death
lesion imaging characteristics
ring enhancing - metastases, abscess/infection, AIDS lymphoma

uniformly enhancing - lymphoma, meningioma

heterogeneously enhancing - glioblastoma
glaucoma drugs
alpha agonists: Epi, brimonidine
decr aqueous humor synthesis from vasoconstriction
mydriasis
NOT for closed angle glaucoma

beta blocker: lol's
decr aqueous humor secretion
no s/e

diuretics: acetazolamide - HCO3 excretion

cholinomimetics: pilocarpine, charbachol, physostigmine
incr outflow of aqueous humor
miosis, spasm
PILOCARPINE in EMERGENCIES

PG: latanoprost
incr outflow of aqueous humor
darkens iris
opiate analgesics
decr synaptic transmission - open K, close Ca
decr AcCh, NE, 5HT, glut, subP

resp depression, miosis, constipation, CNS depression

morphine (mu), enkephalins (delta), dynorphin (kappa)
fentanyl, codeine, heroin, methadone (taper), meperidine (no miosis, Demerol), dextromethorphan (cough), loperamide (diarrhea)
butorphanol
partial opioid agonist, mu-R, for pain without withdrawl
tramadol
weak opioid agonist, works on all NTs, for chronic pain
phenytoin
first line for generalized seizures, also simple + complex partial

first line prophylaxis for status epilepticus

use-dependent Na channel inactivation, decr glut release

do NOT give in pregnancy - teratogen
gingival hyperplasia, SLE syndrome
carbamazepine
first line for generalized seizures, also simple + complex partial

first line for trigeminal neuralgia

Na channel inactivation

s/e: blood dyscrasias/aplastic anemia, SIADH, Steven-Johnson
gabapentin
for simple and complex partial seizures
GABA analog
also peripheral neuropathy, bipolar disorder
phenobarbital barbituate
-arbitals

simple and complex partial, tonic-clonic seizures
incr GABA action, incr Cl conductance DURATION

first line in pregnancy

sedative, anesthesia,
valproate
first line for generalized seizures, also simple and complex partial, myoclonic seizures

incr Na channel inactivation
NMDAR, GABA, K channels too

do NOT give in pregnancy, spina bifida
s/e: hepatotoxicity, neural tube
ethosuximide
first line for absence seizures
T-type Ca channel block

s/e: GI, ha, urticaria, Stevens-Johnson
benzodiazepines (diazepam/lorazepam)
-azepams

first line for acute status epilepticus
also for eclampsia after MgSO4

incr gaba action, incr Cl channel OPENING FREQ

short acting: alpra, TRIAZOLAM, oxa
medium: esta, LORAZEPAM, tema
long (days): chlordiazepoxide, clorazepate, diazepam, flurazepam

THE LONGER ACTING HAVE HIGHER RISKS FOR FALLS IN THE ELDERLY

overdose tx: flumazenil competative antagonist
Steven-Johnson sydrome
malaise, fever, erythema, purpura macules (oral, ocular, genital), epidermal necrosis, sloughing
inhaled anesthesia
lipid soluble to cross BBB or active transport, ideally low solubility in blood

Halothane, NO
cardio suppression, resp depression

mech unknown

s/e: nausea, hepatotoxicity, malignant hyperthermia
IV anesthesia
propofol
rapid induction for short procedures
potentiates GABA

barbituates - thiopental
induction of anesthesia

benzo's - midazolam
adjuct
OD tx: flumazenil

ketamine
PCP analog, blocks NMDARs therefore
glutamate transmission
cardio stimulant, incr cerebral blood flow

opiates
morphine during general anesthesia
OD tx: naloxone
local anesthetics
esters - procaine, cocaine, tetracaine
amides - lidocaine

block activated Na channels

order of block: pain > temp > touch > pressure
NMJ blockers
paralysis in surgery, mechanical ventilation

succinylcholine - depolarizing
antidote: cholinesterase inhibitors

tubocurarine, -urium's - nondepolarizing
competitive AcChR antagonist
antidote: neostigmine
PD drugs
PD has decr Da + incr AcCh

BALSA:

DA agonists:
bromocriptine, L-DOPA/levodopa/carbidopa, amantidine
ergot - bromocriptine, pergolide
non ergot - pramipexole, ropinerole

prevent DA breakdown:
selegiline (MAOB inhibitor, central)
entacapone (COMT inhibitor, peripheral)

anticholinergic:
benzotropine - decr tremor/rigidity
Alzheimers drugs
memantine: NMDAR antagonist
donepezil: AcChE inhibitor
Huntington's drugs
HD has incr DA, decr GABA and AcCh

reserpine + tetrabenaine - decr DA
haloperidol - DA-R antagonist
adrenergic and cholinergic receptor types
alpha1 (NE) - vascular SM, Gq, incr IP3/Ca,
CONTRACTION
agonist - NE, phenylephrine
antagonist - phenoxybenamine, phentolamine,
prazosin
alpha2 (NE) - sympathetic R/GI, Gi, decr AC/cAMP,
RELAX
agonist - clonidine
beta1 (E/NE) - heart, Gs, incr AC/cAMP, incr
CONTRACTION/CO....SA, AV, ventricular m.
agonist - NE, dobutamine
antagonist - propranolol, metoprolol

beta2 (E) - SM/lung, Gx, incr AC/cAMP, RELAX
agonist - albuterol
antagonist - butoxamine, propranolol

nAcChR - preganglionics, adrenal medulla to release E/NE
agonist - carbachol
antagonist - curare, hexamethonium
hexamethonium - ganglion nAcChR blocker, not
NMJ

M1 - CNS
M2 - heart
M3 - glands, SM
antagonist - atropine, mAcChR blocker
key autonomic CNS centers
medulla - vasomotor, resp, swallow, cough, vomit
pons - pneumotaxic
midbrain - micturition
hypothalamus - temp, thirst, food intake
neuron fiber types in PNS
Aalpha
alpha MNs
Ia - spindle afferents
Ib - GTO
Abeta
II - touch/pressure
Agamma
gamma MNs to intrafusal m. fibers
Adelta
III - fast touch, pressure, pain, temp
B
preganglionics
C
postganglionics
IV - slow pain temp
DCMLS
fine touch, pressure, two point, vibration, proprioception
gracilis, cuneatus
second order CROSSES to contralateral thalamus
VPL thalamus - lower body
VPM thalamus - face
pain pathway
nociceptors on free nerve endings, subP NT
inhibited by opioids

referred pain from visceral regions track with overlying somatic nerve segment dermatomes
vision
rhodopsin = opsin protein + retinal molecule (vitA)
vitA deficiency - night blindness
cis-retinal + photon = trans retinal -->
PDE* --> decr cGMP --> close CNG Na channel -->
hyperpolarize --> decr NT release -->
ON center, OFF surround
OFF center, ON surround
depending if glut or GABA

rod/cone - bipolar + horizontal/amacrine - ganglion
optic nerve - LGN thalamus/superior colliculus
occipital lobe
simple cells - bar position/orientation
complex cells - movement/edges

few cones converge on one bipolar for acuity
many rods converge on one bipolar for sensitivity

refractive lens power = diopters, 1/focal distance
emmetropia - normal
hypertropia - farsighted, light focuses behind retina
fix with convex lens
myopia - nearsighted, light focuses in front of retina
fix with concave lens
astigmatism - nonuniform lens curve
fix with cylindric lens
presbyopic - can't accomodate, nearpoint farther away
fix with convex lens
audition
freq - Hz; intensity - dB (log)
middle ear = TM, ossicles MIS, oval window
inner ear = semicircular canal, cochlea, vestibule
perilymph (scala vestibuli) - high Na
endolymph (scala media) - high K

organ of corti sits on basilar membrane
tectorial and basilar membranes --> spiral ganglia --> auditory nerve
inner hair cells - single row, few
out hair cells - parallel rows, many

base of basilar membrane - high f
apex - low f

auditory nerve - lateral lemniscus - inferior colliculus - MGN - ctx
fibers are both crossed and uncross, redundant
contralaterally
vestibular system
semicircular = angular/rotation acceleration
unit is crista ampullaris with cupula filled w fluid
utricle/saccule = linear acceleration + static position
unit is macula with otolithic membrane filled fluid

3 perpendicular semicircular canals + utricle + saccule
filled with endolymph, surrounded by perilymp
hair cells embedded in cupula
kinocilium - single big hair
stereocilia - many small hairs
stereocilia toward kinocilia - excitation
stereocilia away from kinocilia - hyperpolarization

turn head - eyes slowly move in opposite direction, snap back same direction = nystagmus
nystagmus = same direction of rotation
excitation on side toward rotation
inhibition on side opposite rotation

vestibular sx projects to:
4 vestibular nuclei in brainstem
FLOCCONODULAR cerebellum
MLF for eye movements/nystagmus
ctx

test in comatose pt by turning head, if eyes stay fixed with head movement - no vestibular
olfaction
olfactory epithelium receptor cells are TRUE NEURONS
Golf, active - incr cAMP, Na
basal support cells turn over
C fibers - olfactory nerve
trigeminal afferents for painful stim - ammonia
intact with cribiform plate frac because different path

mitral cells in olfactory bulb --> olfactory tract -->
prepiriform cortex
taste
taste buds with microvilli on papillae - NOT NEURONS
ant 2/3 - fungiform papillae, salt/sweet/umami,
facial n. CHORDA TYMPANI branch)
post 1/3 - circumvallate/foliate papillae, sour/bitter
glossopharyngeal n.
post-pharynx/epiglottis - vagus n.

afferents via SOLITARY TRACT to SOLITARY nucleus - VPM thalamus
motor control
MN - fine control, few muscle fibers; large movement, many muscle fibers
small MN - few m. fibers, fire first
large MN - many m. fibers, fire last

force/tension - extrafusal m., recruitment of additional alpha MN MOTOR UNITS

fine adjustments - intrafusal m, gamma MN innervated,+ afferents:
spindles (Ia, II) - intrafusal, detect changes in length
parallel to extrafusal
Ia - velociy change
II - static change

GTO (Ib) - detect changes in tension
series with extrafusal
reflexes
knee - monosynaptic, responds to stretch, Ia, contract
same muscle that was stretched
GTO clasp knife - disynaptic, responds to contraction,
Ib, relaxes agonist muscle (opposite of knee jerk),
contracts antagonist muscle
pain withdraw - polysynaptic, responds to pain,
II/III/IV, ipsilateral flex, contralateral extend

note Renshaw cells in ventral SC - recurrent inhibition, prevent refiring same MN
UMN tracts in SC
pyramidal tracts - coticospinal/corticobulbar

extrapyramidal tracts -
rubrospinal - red n, lateral SC stim flex, inhibit
extensor
lesion above - tonic posturing of neck
pons reticulospinal - ventromedial SC, stim flex and
extensors
lesion - tonic rigidity
medulla reticulospinal - intermediate gray SC,
inhibits flex and extend
vestibulospinal - stim extend, inhibit flex
lesion - tonic rigidity, ataxia
tectospinal - superior colliculus, to cervical SC,
controls neck
key SC lesions
C7 - loss of symp tone to heart
C3 - breathing stops, loss of phrenic control
C1 - death
cerebellum
layers:
inner: granular, filters mossy fiber afferents
middle: Purkinje, inhibitory output
outer: molecular, stellate/basket cells, parallel fibers

inputs:
inf. olive --> climbing fibers --> synapse on Purkinje
complex burst spiking, condition Purkinje
all brainstem/SC --> mossy fibers --> synapse on
Purkinje
simple spikes

outputs: PURKINJE ONLY, INHIBITORY GABA to deep
nuclei and vestibular nuclei
vestibular - balance, eye movement
pons - planning/initiation of movement
SC - rate/force/direction of movement

cerebellum disorder = ataxia, can't rapid alternate movements (dysdiadochokinesia), intention tremor
motor ctx
premotor/supplementary - generate plan for movement, supplementary programs complex sequences

primary motor - execution of movement, motor homunculus, epilepsy
EEG
beta waves = awake, eyes open
alpha waves = awake, eyes closed
slow waves = sleep
sleep
circadian rhythm driven by suprachiasmatic n. hypothalamus, receives input from retina

REM - EEG has awake patterns, loss of muscle tone, pupillary constrict, penile erection

benzodiazepines and incr age - decr REM sleep
hemisphere functions
right - facial expression, spatial tasks

left - language
Wernicke = sensory/understanding aphasia
Broca = motor/speaking aphasia
BBB and CSF
barrier between cerebral capillary blood and CSF
capillary endothelium + choroid plexus epithelium
lipids, gases, and water diffuse unimpeded

CSF ~ blood except
low in K, Ca, glucose, C, protein
high in Mg, creatinine

normal CSF: clear, colorless, low WBC, low protein, low glocose

bac meningitis CSF: cloudy, PMNs, high protein, low glucose

viral meningitis: clear/cloudy, elevated WBC with lymphocyte predominance, mildly elevated protein, normal glucose

SAH CSF: frank blood, xanthochromic, RBC, slightly elevated protein, normal glucose

space occupying lesions can incr CSF opening pressure
temperature regulation
anterior hypothalamus:
integrates core temp inputs and compares this to
set-point
pyogens incr set-point: high IL1 --> incr PG
ASA --> block COX/decr PG --> decr set
point/fever
steroid --> block AA from PL --> decr PG --> decr
set point/fever

heat generators:
TH --> incr BMR
sympathetic --> brown fat*
posterior hypothalamus --> MN --> shivering

heat shunters:
anterior hypothalamus --> decr symp tone -->
dilates vessels, AV shunting
symp mAcChR in sweat glands

heat exhaustion - excessive sweating with volume loss
heat stroke - temp reaches point of tissue damage,
impaired heat control mechanisms

malignant hyperthermia - rxn to anesthetics, heat production by skel muscle, incr O2 intake
spinal shock
SC transection --> temporary loss of all local reflexes below the lesion
anesthesia stages
stage 1 = analgesia, conscious

stage 2 = excitement, delirium, violent behavior, incr BP/resp/HR, retching, vomiting, etc

stage3 = no eye movement, fixed pupils, regular resps, relax skel muscle

stage 4 = resp depression, decr vasomotor
inhaled anesthetics
MAC = minimum alveolar concentration, required to stop movement in 50% of pts = potency
small MAC = more potent
MAC values are additive, use lower dose if combo
MAC is lower in elderly, use lower dose
blood/gas partition coefficient = solubility in blood
high coefficient incr time to induction/recovery bc
blood holds onto anesthetic instead of dumping it
into the brain
lipid soluble = more bioavailable

inhaled anesthetics decr response to PCO2, incr ICP, relax SM

many are halogenated hydrocarbons, except NO

- halothane - smallest MAC, high blood/gas partition
decr HR, decr renal/hepatic perfusion
risk of MALIGNANT HYPERTHERMIA, can be familial
antidote = DANTROLENE
risk of hepatitis, but not in kids
risk of arrhythmias
- NO - largest MAC, low blood/gas partition
coefficient, expands trapped gas
- isoflurane (-fluranes) - incr bronchiolar secretions,
bronchiolar spasms, incr HR
IV anesthetics
propofol - rapid induction and recovery, only short
procedures, antiemetic
fentanyl - opiod
risk of chest wall rigidity
ketamine - blocks NMDARs
causes dissociative amnesia (unconcious, but looks
awake)...delirium, hallucinations, incr cerebral BF
heart stimulant, vivud dreams, hallucinations
midazolam - benzodiazepine
anterograde amnesia
Flumazenil - antidote for resp depression
thiopental - barbituate, for induction
(decr cerebral blood flow, resps, and BP)
risk of laryngospasm - watch in asthmatics
etomidate - very CARDIAC STABLE
local anesthetics
locals are weak bases - inhibit Na channels
active in ionized form to bind Na channels
all vasodilate except cocaine
most sensitive: small, myelinated fibers, w/ high
firing rate (types B/C)
s/e (more common in esters): hypotension (not
cocaine), nystagmus, seizures, dizzy, atopy
amide: lidocaine/prilocaine
>1 "i" in name
metabolized by amidases in liver
esters: cocaine/benzocaine/procaine
1 "i" in name
metabolized by esterases in tissues/blood
note cocaine is the only drug that vasoconstricts

can use with epinephrine in combo to locally vasoconstrict and limit systemic effects
BUT do not use in digits, nose, ears, penis..end
arteries
opioids
works best for persistent pain
POMC derived - POMC enzymatic cleavage
(ACTH, MSH are also from POMC)

endogenous:
enkephalin - binds delta-R
dynorphin - binds kappa-R
betaendorphin - binds mu-R
opioid-Rs in:
midbrain - periaqueductal gray, activates raphae n.,
descending inhibition
dorsal SC: primary afferents, inhibits subP

opioid-R's: GPCRs
presynaptic opioid-R's: inhibit Ca flux, decr NT release
postsynaptic opioid-R's: incr K efflux, hyperpolarize

prototype: morphine
incr histamine degranulation from mast cells -->
hypotension, pruritis
incr ICP, head trauma contraindicates
decr peristalsis --> constipation
use loperamide, diphenoxylate for diarrhea
incr tone biliary, bladder, ureter
except meperidine
incr urinary retention - incr ADH
decr uterine contractions
miosis - seen in OD, incr parasymp pupil constrictor*
except meperidine
incr emesis - chemoR trigger zone* in area postrema
resp depression - decr sensitivity of CO2 sensors
common cause of death
antidote = naloxone, mu-R antagonist

dextromethorphan - for cough, a synthetic
heroin and fantanyl - highly lipid, cross BBB fast
morphine is least lipo
clonidine for heroin withdrawl - alpha2 agonist
naltrexone - for alcoholics, decr cravings
methadone - synthetic, for withdrawl and rehab
meperidine - synthetic

weak opiates: codeine, tramadol
partial agonists: buprenorphine, butorphanol

morphine metabolized by phase II
tolerance not developed for: constipation, miosis

withdrawl ssx: tears, runny nose, diaphoretic, anxiety, pain, diarrhea

do not give meperidine or dextromethorphan with MAOIs --> seratonin syndrome
opioids
works best for persistent pain

endogenous:
enkephalin - binds delta-R
dynorphin - binds kappa-R
betaendorphin - binds mu-R
opioid-Rs in:
midbrain - periaqueductal gray, activates raphae n.,
descending inhibition
dorsal SC: primary afferents, inhibits subP

opioid-R's: GPCRs
presynaptic opioid-R's: inhibit Ca flux, decr NT release
postsynaptic opioid-R's: incr K efflux, hyperpolarize

prototype: morphine
incr histamine degranulation from mast cells -->
hypotension, pruritis
incr ICP, head trauma contraindicates
decr peristalsis --> constipation
use loperamide, diphenoxylate for diarrhea
incr tone biliary, bladder, ureter
except meperidine
incr urinary retention - incr ADH
decr uterine contractions
miosis - seen in OD, incr parasymp pupil constrictor*
except meperidine
incr emesis - chemoR trigger zone* in area postrema
resp depression - decr sensitivity of CO2 sensors
common cause of death
antidote = naloxone, mu-R antagonist

dextromethorphan - for cough, a synthetic
heroin and fantanyl - highly lipid, cross BBB fast
morphine is least lipo
clonidine for heroin withdrawl - alpha2 agonist
naltrexone - for alcoholics, decr cravings
methadone - synthetic, for withdrawl and rehab
meperidine - synthetic

weak opiates: codeine, tramadol
partial agonists: buprenorphine, butorphanol

morphine metabolized by phase II
tolerance not developed for: constipation, miosis

withdrawl ssx: tears, runny nose, diaphoretic, anxiety, pain, diarrhea

do not give meperidine or dextromethorphan with MAOIs --> seratonin syndrome
anxiolytics and sedatives
action sequence: sedation-anxiolysis-hypnosis-
anesthesia-medullary depression-coma

ethanol - metabolized by alcohol dehydrog to
acetaldehyde, then acetaldehyde dehydrog to acetate
ha/hypotension/NV hangover - from acetaldehyde
disulfiram - inhibits acetaldehyde dehydrog, incr
acetaldehyde, for neg conditioning

GABA
GABA-R has 5 subunits, GABA binds alpha
incr Cl influx, K efflux --> hyperpol
benzodiazepines bind gamma, need GABA to activate
incr FREQ of Cl channel opening
barbituates bind beta, need GABA to activate
incr DURATION of Cl channel opening
baclofen - binds GABA-B, muscle relaxant

benzo's:
prototype - chlordiazepoxide
diazepam, lorazepam - long acting
midazolam, triazolam, oxazepam - short acting
roofie = flunitrazepam
anticonvulsants = diazepam, clonazepam
alcohol withdrawl tx: long acting benzo's
sleep aids: temaepam, triazolam
anxiolytics: diazepam, lorazepam...long acting

benzo s/e: obtunded, ataxia, amnesia, decr resp
benzo withdrawl: insomnia, anxiety, agitation, seizure
benzo antidote: flumazenil - benzo-R antagonist
benzo OD: add barbituates and alcohol

non-benzo sleep aids (made for this action only):
eszopiclone, zolpidem (ambien), zaleplon
antidote = flumazenil

barbituates
phenobarbital, pentobarbital - long acting
ambobarbital, secobarbital - short acting
for sedation, hypnosis
thiopental - ultrashort acting, induce anesthesia

barbituates for seizures - partial, generalized,
tonic/conic
CYP450 inducing
barbituate s/e: obtunded, resp/cardio depression,
addiction
barbituate withdrawl: insomnia, tremor, anxiety, NV, seizures
prevent with long acting benzos
anxiolytics and sedatives
action sequence: sedation-anxiolysis-hypnosis-
anesthesia-medullary depression-coma

ethanol - metabolized by alcohol dehydrog to
acetaldehyde, then acetaldehyde dehydrog to acetate
ha/hypotension/NV hangover - from acetaldehyde
disulfiram - inhibits acetaldehyde dehydrog, incr
acetaldehyde, for neg conditioning

GABA
GABA-R has 5 subunits, GABA binds alpha
incr Cl influx, K efflux --> hyperpol
benzodiazepines bind gamma, need GABA to activate
incr FREQ of Cl channel opening
barbituates bind beta, need GABA to activate
incr DURATION of Cl channel opening
baclofen - binds GABA-B, muscle relaxant

benzo's:
prototype - chlordiazepoxide
diazepam, lorazepam - long acting
midazolam, triazolam, oxazepam - short acting
roofie = flunitrazepam
anticonvulsants = diazepam, clonazepam
alcohol withdrawl tx: long acting benzo's
sleep aids: temaepam, triazolam
anxiolytics: diazepam, lorazepam...long acting

benzo s/e: obtunded, ataxia, amnesia, decr resp
benzo withdrawl: insomnia, anxiety, agitation, seizure
benzo antidote: flumazenil - benzo-R antagonist
benzo OD: add barbituates and alcohol

non-benzo sleep aids (made for this action only):
eszopiclone, zolpidem (ambien), zaleplon
antidote = flumazenil

barbituates
phenobarbital, pentobarbital - long acting
ambobarbital, secobarbital - short acting
for sedation, hypnosis
thiopental - ultrashort acting, induce anesthesia

barbituates for seizures - partial, generalized,
tonic/conic
CYP450 inducing
barbituate s/e: obtunded, resp/cardio depression,
addiction
barbituate withdrawl: insomnia, tremor, anxiety, NV, seizures
prevent with long acting benzos
sleep aids OTC
sedating antihistamines

diphenhydramine, doxylmine, hyrdroxyzine
sleep aids OTC
sedating antihistamines

diphenhydramine, doxylmine, hyrdroxyzine
antidepressants used for sedation and hypnosis
trazodone, amitriptyline = TC antidepressants, incr 5HT
partial agonist of 5HT1A-R, for generalized anxiety disorders
buspirone
NO SEDATION, no addiction, no tolerance, no withdrawl
not anticonvulsant, not muscle relaxant

takes 1-2 weeks
partial agonist of 5HT1A-R, for generalized anxiety disorders
buspirone
no sedation, no addiction, no tolerance, no withdrawl
not anticonvulsant, not muscle relaxant

takes 1-2 weeks
MAOI antidepressants
depression - biogenic amine theory = low 5HT, NE
MAO-A = inactivates 5HT, NE
MAO-B = inactivates NA
nonselective MAOIs --> incr 5HT, NE, DA
tranylcypromine, phenelzine, isocarboxazid
for atypical depression, takes weeks to work, wait
weeks before switching
s/e: orthostatic hypotension, blurry vision,
constipation, urinary retention, drowsy

selective MAO-B inhibitor - Selegiline, for PD

serotonin syndrome - opiate + MAOI
rigidity, diaphoresis, hyperthermia, seizure
+dextromethorphan - cough
+meperidine - analgesic

hypertensive crisis - MAOI + tyramine (ingested)
htn, ha, tachy, NV, stroke, arrhythmia
MAOI antidepressants
depression - biogenic amine theory = low 5HT, NE
MAO-A = inactivates 5HT, NE
MAO-B = inactivates NA
nonselective MAOIs --> incr 5HT, NE, DA
tranylcypromine, phenelzine, isocarboxazid
for atypical depression, takes weeks to work, wait
weeks before switching
s/e: orthostatic hypotension, blurry vision,
constipation, urinary retention, drowsy

selective MAO-B inhibitor - Selegiline, for PD

serotonin syndrome - opiate + MAOI
rigidity, diaphoresis, hyperthermia, seizure
+dextromethorphan - cough
+meperidine - analgesic

hypertensive crisis - MAOI + tyramine (ingested)
htn, ha, tachy, NV, stroke, arrhythmia
TCA antidepressants
inhibits 5HT + NE reuptake
amitryptiline, imipramine, clomipramine
metabolites specifically inhibit NE reuptake:
amitryptiline-->nortriptyline
imipramine-->desipramine
for migraines and neuropathic pain - amitriptiline
for OCD - clomipramine
for pediatric nocturnal enuresis - imipramine
incr bladder spincter contraction
takes weeks

more s/e with TCA than SSRI
s/e:
central/peripheral mAcChR block - tachy,
delirium, dilated, flushing, hyperthermia
ileus, urinary retention
alpha1R inhibition - peripheral vasodilate,
orthostatic
cardiac fast Na channel inhibition -
conduction defects, arrhythmias,
hypotension
NE/5HT reuptake inhibition - seizure,
tremor
histamine R inhibition - sedation
TCA antidepressants
inhibits 5HT + NE reuptake
amitryptiline, imipramine, clomipramine
metabolites specifically inhibit NE reuptake:
amitryptiline-->nortriptyline
imipramine-->desipramine
for migraines and neuropathic pain - amitriptiline
for OCD - clomipramine
for pediatric nocturnal enuresis - imipramine
incr bladder spincter contraction
takes weeks

more s/e with TCA than SSRI
s/e:
dry mouth, blurry vision, urinary retention,
constipation, glaucoma, arrhythmia, seizure, tachy,
sedation
toxicity: coma, convulsions, cardiotoxicity
antidote - activated charcoal, Nabicarb
also inhibit other receptors:
anticholinergic - inhibits mAcChR
blocks adrenergicR
blocks histamineR
atypical antidepressants
trazodone/nefazodone - 5HT reuptake inhib
s/e: priapism

bupropion - incr DA, 5HT, NE by unknown
also for smoking cessation, OCD
does not affect sexual function like SSRI
contraindicated in epilepsy - decr seizure threshold

mirtazapine - s/e is weight gain

yohimbine - also for erectile dysfunction, alpha2 antagonist
atypical antidepressants
trazodone/nefazodone - 5HT reuptake inhib
s/e: priapism

bupropion - incr DA, 5HT, NE by unknown
also for smoking cessation, OCD
does not affect sexual function like SSRI
contraindicated in epilepsy - decr seizure threshold

mirtazapine - s/e is weight gain

yohimbine - also for erectile dysfunction, alpha2 antagonist
SSRI/SNRI antidepressants
SSRIs: fluoxetine, paroxetine, sertraline, citalopram
floxetine - longest acting, also for premenstrual
dysphoric disorder, bulimia, OCD, panic, mutilism
citalopram, sertraline - fewest drug interactions

big s/e: sexual dysfunction
also, agitation, anxiety, seizures, NVD, sedation,
serotonin syndrome
CYP450 inhibitor
DO NOT cause arrhythmias like TCA

paroxetine - also for social/generalized anxiety, PTSD
venlafaxine - s/e is htn
duloxetine - SSNRI (5HT and NE)
SSRI/SNRI antidepressants
SSRIs: fluoxetine, paroxetine, sertraline, citalopram
floxetine - longest acting, also for premenstrual
dysphoric disorder, bulimia, OCD, panic, mutilism
citalopram, sertraline - fewest drug interactions

big s/e: sexual dysfunction
also, agitation, anxiety, seizures, NVD, sedation,
serotonin syndrome
CYP450 inhibitor
DO NOT cause arrhythmias like TCA

paroxetine - also for social/generalized anxiety, PTSD
venlafaxine - s/e is htn
duloxetine - SSNRI (5HT and NE)
bipolar aka manic depression drugs
Li - unknown MoA, narrow therapeutic window
eliminated by KINDEY, like Na, follows Na
in kidney
toxicity exacerbated by low Na, thiazides,
ACE-I, NSAIDs (NOT loop diuretics)

s/e:
nephrogenic diabetes insipidus (ADH antagonist)
baby of mom using Li - Ebstein anomaly, tricuspid
valve malformation
hypothyroid (inhibs 5-deiodinase), tremor,
acne, seizures, ataxia
coadmin with amiloride for d. insipidus

carbamazepine, valproic acid, benzos, gabapentin, topiramate
bipolar aka manic depression drugs
Li - unknown MoA, narrow therapeutic window
eliminated like Na, follows Na in kidney
toxicity exacerbated by low Na
s/e:
nephrogenic diabetes insipidus (ADH antagonist)
baby of mom using Li - Ebstein anomaly, tricuspid
valve malformation
hypothyroid (inhibs 5-deiodinase), tremor,
acne, seizures, ataxia
coadmin with amiloride for d. insipidus

carbamazepine, valproic acid, benzos, gabapentin, topiramate
antipsychotics
block central D2Rs

schizophrenia psychosis - excess DA
positive sx: hallucinations, delusion
negative sx: flat affect, social withdrawl, speech prob

typical antipsychotics - inhibit DA-R in mesolimbic sx
haloperidol, chlorpromazine, thioridazine
also for Tourettes - haloperidol
extrapyramidal sx: PD like - dystonia, akinesia
(motor restlessness), rigid, tremor, bradykinesia,
tardive dyskinesia (from DA-R hypersensitivity)
prolactinemia (inhib DA-R in ant. pituitary)
s/e mostly haloperidol b/c strongest
thioridazine + chlorpromazine - less extrapyramidal
sx because also anticholinergic (mAcChR)...but
other sx --> dry mouth, blurry vision, constipated
tx extrapyramidal sx with benzotropine, amantidine,
diphenydramine (anticholinergics)
chlorpromazine - for intractable hiccups
thioridazine s/e: priapism, agranulocytosis, blue-
gray skin, seizures
chlorpromazine - low potency, NON neuro s/e
haloperidol - high potency, NEURO s/e

atypical antipsychotics - inhibit 5HT-Rs
first line bc less s/e
risperidone, clozapine, aripiprazole, olanzapine
mostly for neg sx
clozapine - third line, for intractable shizophrenia
s/e: agranulocytosis (low WBC), seizure, sialorrhea
risperidone s/e: gynecomastia,
PROLACTINEMIA --> AMENORRHEA,
weight gain
clozapine + olazapine - cause weight gain

life threatening s/e: neuroleptic malignant syndrome
ssx: fever, rigid, AMS, cardio instability
tx: dantrolene + bromocriptine (DA agonsits)
antipsychotics
schizophrenia psychosis - excess DA
positive sx: hallucinations, delusion
negative sx: flat affect, social withdrawl, speech prob

typical antipsychotics - inhibit DA-R in mesolimbic sx
haloperidol, chlorpromazine, thioridazine
also for Tourettes - haloperidol
extrapyramidal sx: PD like - dystonia, akinesia
(motor restlessness), rigid, tremor, bradykinesia,
tardive dyskinesia (from DA-R hypersensitivity)
prolactinemia (inhib DA-R in ant. pituitary)
s/e mostly haloperidol b/c strongest
thioridazine + chlorpromazine - less extrapyramidal
sx because also anticholinergic (mAcChR)...but
other sx --> dry mouth, blurry vision, constipated
tx extrapyramidal sx with benzotropine, amantidine,
diphenydramine (anticholinergics)
chlorpromazine - for intractable hiccups
thioridazine s/e: priapism, agranulocytosis, blue-
gray skin, seizures

atypical antipsychotics - inhibit 5HT-Rs
risperidone, clozapine, aripiprazole, olanzapine
mostly for neg sx
clozapine - third line, for intractable shizophrenia
s/e: agranulocytosis (low WBC), seizure, sialorrhea
risperidone s/e: gynecomastia,
PROLACTINEMIA --> AMENORRHEA
clozapine + olazapine - cause weight gain

life threatening s/e: neuroleptic malignant syndrome
ssx: fever, rigid, AMS, cardio instability
tx: dantrolene + bromocriptine (DA agonsits)
PD drugs
PD = low DA, high AcCh in sub. nigra and striatum
bradykinesia, rigidity, tremor, gait, posture

anti muscarinics (mAcChR)
for tremor + rigidity, not bradykinesia
benztropine, tirhexyphenidyl
s/e: dry mouth, blurry vision, constipation, mydriasis

incr DA
amantidine - DA reuptake inhib, incr DA release
also for influenza A
helps with bradykinesia, not tremors
s/e: livedo reticularis - patchy red macules
selegiline - MAO-B inhibitor
selegiline metabolized to amphetamines
s/e: stim heart
ergots
bromocriptine, pergolide
bromocriptine also for prolactinoma
s/e: ha, dizzy, N, orthostatic, dyskinesia,
hallucinations, pschosis
non-ergots - preferred over ergots
pramipexole, ropinirole
s/e: sedation, syncope, NV, hallucinations,
dyskinesia
levodopa - precursor to DA that crosses BBB (unlike
DA)
not useful in very advanced dz bc need DA neuron
to convert to DA
on/off effect - move, then frozen
apomorphine is antidote - fast acting DA agonist
s/e: anorexia, NV, tachy, discolored urine/saliva,
hallucination, mydriasis, dyskinesia, incr IOP
dont coadmin with vitB6 - incr levodopa metabo

anti-metabolics
DDC inhibitor - inhibs levodopa to DA metabolism
carbidopa, first line, acts PERIPHERALLY
COMT inhibitor - inhibs L-dopa metabolism
tolcapone, entacapone
s/e: brown-orange urine, hallucinations, ND,
cramps
tolcapone - hepatotoxic
PD drugs
PD = low DA, high AcCh in sub. nigra and striatum
bradykinesia, rigidity, tremor, gait, posture

anti muscarinics (mAcChR)
for tremor + rigidity, not bradykinesia
benztropine, tirhexyphenidyl
s/e: dry mouth, blurry vision, constipation, mydriasis

incr DA
amantidine - DA reuptake inhib, incr DA release
also for influenza A
helps with bradykinesia, not tremors
s/e: livedo reticularis - patchy red macules
selegiline - MAO-B inhibitor
selegiline metabolized to amphetamines
s/e: stim heart
ergots
bromocriptine, pergolide
bromocriptine also for prolactinoma
s/e: ha, dizzy, N, orthostatic, dyskinesia,
hallucinations, pschosis
non-ergots - preferred over ergots
pramipexole, ropinirole
s/e: sedation, syncope, NV, hallucinations,
dyskinesia
levodopa - precursor to DA that crosses BBB (unlike
DA)
not useful in very advanced dz bc need DA neuron
to convert to DA
on/off effect - move, then frozen
apomorphine is antidote - fast acting DA agonist
s/e: anorexia, NV, tachy, discolored urine/saliva,
hallucination, mydriasis, dyskinesia, incr IOP
dont coadmin with vitB6 - incr levodopa metabo

anti-metabolics
DDC inhibitor - inhibs levodopa to DA metabolism
carbidopa, first line, acts PERIPHERALLY
COMT inhibitor - inhibs L-dopa metabolism
tolcapone, entacapone
s/e: brown-orange urine, hallucinations, ND,
cramps
tolcapone - hepatotoxic
anticonvulsants
partial seizures: simple, complex
generalized seizures: tonic/clonic, absence, myoclonic
status epilepticus: >30 min seizure, or no full recovery

most common is tonic/clonic (grand mal), associated with febrile seizure
hyperventilation lowers seizure threshold by incr pH

phenytoin - blocks Na channels in inactivated state
for simple/complex partial, tonic clonic, status
epilepticus
also antiarrhythmic
induces CYP450
s/e: diplopia, sedation, ataxia, megaloblastic anemia
gingival hyperplasia, nystagmus, penias, SJ
syndrome
teratogen - not in preg
(also cause gingival hyperplasia - cyclosporin,
nifedipine)

carbamazepine - blocks Na channels
for simple/complex partial, tonic clonic
also for manic depression, trigeminal neuralgia
induces CYP450
s/e: SJ syndrome, SIADH, hepatotoxic, diplopia,
anemia, alopecia, pancreatitis
teratogen - not in preg

valproate - blocks Na, Ttype Ca channels, incr GABA
for epilepsy, simple/complex partial, tonic clonic,
absence, myoclonic
also for manic depression, migraine
inhibs CYP450
s/e: alopecia, hepatotoxic, weight gain, rash, penias
teratogen - not in preg, neural tube defects

phenobarbital - for partial and tonic/clonic in preg

diazepam, lorazepam - for status epilepticus

ethosuximide - for absence, blocks Ttype Ca channels
in thalamus
s/e: EPS, NVD, SJ syndrome

clonazepam - for myoclonic, absence

decr efficacy of oral contraceptives via CYP450 induction - phenytoin, carabamazepine

new antiepileptics:
gabapentin, lamotrigine, topiramate, tiagabine, vigabatrin, levetiracetam
no drug-drug interactions: levetiracetam, gabapentin
GABApentin structure like GABA, doesnt bind R
also for migraine, neuropathic pain, manic
depression, insomnia, chronic pain
s/e: sedation, ataxia
topiramate: blocks AMPA-Rs, incr GABA effects,
blocks VG Na channels
s/e: blocks CA-->met acidosis
AMS, sedation, weight loss, renal stones
also for migraine, manic depression, neuropath
pain
anticonvulsants
partial seizures: simple, complex
generalized seizures: tonic/clonic, absence, myoclonic
status epilepticus: >30 min seizure, or no full recovery

most common is tonic/clonic (grand mal), associated with febrile seizure
hyperventilation lowers seizure threshold by incr pH

phenytoin - blocks Na channels in inactivated state
for simple/complex partial, tonic clonic, status
epilepticus
also antiarrhythmic
induces CYP450
s/e: diplopia, sedation, ataxia, megaloblastic anemia
gingival hyperplasia, nystagmus, penias, SJ
syndrome
teratogen - not in preg
(also cause gingival hyperplasia - cyclosporin,
nifedipine)

carbamazepine - blocks Na channels
for simple/complex partial, tonic clonic
also for manic depression, trigeminal neuralgia
induces CYP450
s/e: SJ syndrome, SIADH, hepatotoxic, diplopia,
anemia, alopecia, pancreatitis
teratogen - not in preg

valproate - blocks Na, Ttype Ca channels, incr GABA
for epilepsy, simple/complex partial, tonic clonic,
absence, myoclonic
also for manic depression, migraine
inhibs CYP450
s/e: alopecia, hepatotoxic, weight gain, rash, penias
teratogen - not in preg, neural tube defects

phenobarbital - for partial and tonic/clonic in preg

diazepam, lorazepam - for status epilepticus

ethosuximide - for absence, blocks Ttype Ca channels
in thalamus
s/e: EPS, NVD, SJ syndrome

clonazepam - for myoclonic, absence

decr efficacy of oral contraceptives via CYP450 induction - phenytoin, carabamazepine

new antiepileptics:
gabapentin, lamotrigine, topiramate, tiagabine, vigabatrin, levetiracetam
no drug-drug interactions: levetiracetam, gabapentin
GABApentin structure like GABA, doesnt bind R
also for migraine, neuropathic pain, manic
depression, insomnia, chronic pain
s/e: sedation, ataxia
topiramate: blocks AMPA-Rs, incr GABA effects,
blocks VG Na channels
s/e: blocks CA-->met acidosis
AMS, sedation, weight loss, renal stones
also for migraine, manic depression, neuropath
pain
migraine drugs
propanolol
triptans
note can cause coronary vasospasm, hypertensive
crisis
ergot alkaloids - cerebral vasosconstriction
migraine drugs
propanolol
triptans
note can cause coronary vasospasm, hypertensive
crisis
ergot alkaloids - cerebral vasosconstriction
serotonin syndrome
MAOI + SSRI

tachy, diaphoretic, myoclonic twitches, generalized tonic clonic seizure

tx: CYPROHEPTADINE - 5HT-R ANTAGONIST
serotonin syndrome
MAOI + SSRI

tachy, diaphoretic, myoclonic twitches, generalized tonic clonic seizure
hypertensive crisis
MAOI + tyramine (cured meat, cheese)

super high BP
hypertensive crisis
MAOI + tyramine (cured meat, cheese)

super high BP
drug causing increase in peak airway pressure
fentanyl - synthetic opioid, used in combo with anesthesia
drug causing increase in peak airway pressure
fentanyl - synthetic opioid, used in combo with anesthesia
arnold chiari malformation
underdeveloped posterior fossa

AC type 1 = cerebellar tonsils extend through foramen magnum into canal --> ataxia
can be asymptomatic in infants, present in
adulthood as ataxia

AC type 2 = more severe, present in infancy, vermis and medulla extend into canal --> associated with myelomeningocele, hydrocephalus, plus difficulty swallowing, dysphonia, stridor, apnea...medullary sx
alzheimers disease
APP - chr21
note risk incr with trisomy 21, early onset
familial form is early onset (30-60 yo)
neurofibrillary tangles, amyloid plaques, cerebral atrophy

loss AcCh/ChAT
tx with AcChE inhibitors - tacrine, donepezil,
rivastigmine, galantamine
tacrine only one shown to slow memory loss

excitotoxicity via NMDARs
tx with NMDAR antagonist - memantine
brown sequard syndrome
hemicord lesion

ipsilateral spastic paralysis
ipsilateral vibration/position loss
contralateral pain temp loss
bilateral pain/temp at lesion site

T10 = navel

lesion above T1 --> unilateral Horners - ptosis, miosis, anhidrosis
corneal abrasion
eye pain, more with movement, possible without any obvious foreign body but from previous scratch

pain from V1
V1 is also corneal blink reflex afferents --> bilateral to facial nucleus for blink with orbicularis oculi m.
eye embyrology
neuroectoderm --> optic cup --> retina, iris, ciliary body

lens from surface neuroectoderm

inner layer of the cornea from mesenchyme
outer layer of the cornea from surface ectoderm
central cord syndrome
upper extremity weakness exceeding lower extremity weakness, variable sensory loss below lesion levels

watershed zone in central cord is susceptible - between anterior spinal a. and posterior spinal a's
think: trauma, hypotension, hypoperfusion, edema

local reflexes can be moderately diminished:
biceps reflex - C5/C6
brachioradialis reflex - C6
triceps reflex - C7
craniopharyngioma
bimodal, typically in children, also in older 50s
Rathke's pouch derived - ectoderm, mouth--> adenohypophysis
suprasellar, cystic, calcified mass

bitemporal hemianopia, growth retardation, hypothyroid, central diabetes insipidus

ddx: optic glioma, meningioma, pituitary adenoma, mets
laryngeal nerve
CNX - tracks with jugular v. into mediastinum

left recurrent laryngeal nerve - branches off vagus and wraps under aorta posteriorly the arch

right recurrent laryngeal nerve - brnaches off vagus and wraps under subclavian posteriorly

recurrent laryngeal nerve innervates all intrinsic laryngeal m's
except cricothyroid (innervated by external laryngeal
nerve)
femoral neuropathy
lumbar plexus --> L2-L4 = femoral n. --> femoral triangle
(sartorius, inguinal ligament, adductor longus)

motor:
hip flexors - L2-L3 (segment above the inguinal
ligament)
quads - L3-L4

sensory branches:
anterior and medial thigh
lateral thigh via lateral femoral cutaneous n.
anterior knee, leg, foot via saphenous n.

note adduction spared = adductor longus, brevis, magnus, innervated by obturator n. (L2-L4)
guillame barre
symmetric, ascending paresthesias, weakness, associated with viral illness, GI infection, allergic rxn
associated with campylobacter and herpes

acute inflammatory demyelinating polyradiculopathy
CSF - HIGH protein, normal cells (albuminocytologic dissociation)

can also see papilledema, blurred optic disk, vascular congestion

can progress to chronic inflammatory demyelinating polyradiculopathy
hydrocephalus
communicating - overproduction
choroid plexus papilloma
noncommunicating - blockage
impaired resorption (obstruction, villi disruption)
blockage of CSF flow through Monroe, Sylvius,
Magende, Luschka

CSF produced by choroid plexus epithelium in the ventricles, CSF returned to the blood via pinocytosis by arachnoid villus cells in the superior sagittal sinus

fourth ventricle communicates with subarachnoid via Luschka and Magendie

capillary and choroid plexus endothelium form BBB - tight junctions, regulated transport
trinucleotide repeat dz's
huntingtons, FXS, myotonic dystrophy, spinocerebellar ataxia types I/II
anopias
radiations from the LGN:
inferior radiations = inferior retina = superior
visual field
inferior radiations = Meyer's loop in temporal lobe
Meyer's loop lesion = pie in the sky
superior radiations = superior retina = inferior
visual field
superior radiations = parietal lobe

synapse in occipital lobe near calcarine fissure
inferior radiations - synapse inferior to fissure
superior radiations - synapse superior to fissure
psammoma bodies
laminated, concentric calcified concretions
formed by:
meningiomas (head)
papillary adenocarcinoma (thyroid)
malignant mesothelioma (thorax)
serous papillary cystadenocarcinoma (ovary)
otitis media
painful ear, runny nose, sinus pressure, dizzy, fever, bulging red TM

typically secondary to viral URI that travels via eustachian tube:
resp syncytial virus, rhinovirus, influenza, adeno
or bacteria:
strep pneumo, h flu, GAS

tympanic membrane derived from first pharyngeal membrane (tissue between pharyngeal groove/cleft and pharyngeal pouch

only the first pharyngeal membrane is retained postnatally, rest are obliterated during development
meningitis
typically travels via oropharynx --> blood --> arachnoid --> meninges

will see bugs in CSF, or if viral will only see lymphocytes

most common viral: echo, coxsackie, adeno, CMV,
HIV, EBV, HSV
CSF - normal to high ICP, high WBC, normal protein, NORMAL sugar

most common bacs:
infants - GBS, e coli, listeria
kids/adults - neisseria meningitidis, strep pneumo,
h flu-B
CSF: high ICP, high PMNs, high protein, low sugar

most common fungal: cryptococcus, think AIDS
CSF: high ICP, high WBC, high protein, low sugar
ear embryology
tympanic membrane derived from first pharyngeal membrane (tissue between pharyngeal groove/cleft and pharyngeal pouch

only the first pharyngeal membrane is retained postnatally, rest are obliterated during development

malleus - first branchial arch
incus - first branchial arch
stapes - second branchial arch

tensor tympani dampens malleus, V3
stapedius dampens stapes, VII
neurofibromatosis type 1
neurocutantous dz
AD, NF1 gene, chr 17, familial for denovo

hyperpigmented macules - cafe-au-lait
neurofibromas - soft fleshy tumors, typically develop
in adolescence
freckling in axilla and groin
Lisch nodules - iris, raised/pigmented hamartomas
high risk - optic gliomas anywhere on optic tract, astrocytomas, gliomas, neurofibrosarcomas
myasthenia gravis
typically older, idiopathic
sx worse as the day progresses, with use:
FATIGUE, strabismus, ptosis, diplopia, dysarthria, difficulty chewing, difficulty swallowing, proximal muscle weakness

AI against AcChR, decr NMJ transmision-->weakness

associated with thymoma, thymectomy is tx

similar to Lambert-Eaton syndrome in presentation, AI against VG Ca channels, except LE syndrome better with activity when more Ca released...opposite of MG
neurofibromatosis type 2
neurocutaneous dz
AD, merlin gene, chr 22

acoustic neuroma (sensorineural hearing loss)
+ cafe au lait spots, blurry vision, juvenile cataracts
hyperprolactinemia
prolactin secreting tumor from AP =
amenorrhea + infertility + galactorrhea
...watch for bitemporal hemianopia

DA from hypothalamus inhibits prolactin release

tx: DA analog - bromocriptine, transphenoidal surgery

rule out pregnancy!
infective endocaridits ssx
from valvular vegetation thrombi --> emboli

splinter hemorrhages, oslers nodes on finger/toes, Roth spots on retina
cherry red spots
Metabolic Storage Diseases:
Mucopolysaccharidosis
Hurler's disease
Tay-Sachs disease
MPS VII
Farber's disease
GM1 gangliosidoses
Juvenileeroid
Niemann Pick's disease
Sandoff's disease
Shprintzen-Goldberg syndrome
Lysosomal Storage Diseases

Congenital Developmental Diseases :
Amaurosis, congenital, Leber's

Hereditary/ Familial:
leukodystrophy, Krabbe's

Degenerative:
Metachromatic leukodystrophy

Vascular:
central retinal artery occlusion

Drugs:
Quinine toxicity
Dapsone toxicity

Poisoning:
Carbon monoxide
Methanol
syncope
commonly from volume depletion --> orthostatic hypotension

vasovagal, cardiogenic (arrhythmia, stenosis, tamponade, PE, dissection), TIA, orthostatic hypotension

body reacts normally to orthostatic changes with a sympathetic discharge to increase PVR, VR, and CO to minimize the drop in BP
TIA
typically from embolic stroke - high risk with:
carotid stenosis, atherosclerosis, a fib, MV vegetations/repair
can see cerebral edema
cerebral edema
ssx:
loss of gray/white junction, loss of prominent sulci, mass effect evidence, decrease in size of lateral ventricles, uncal herniation
vascular dementia
recurrent strokes -->stepwise decline in fxn

two types:
multi-infarct dementia -
multiple large infarcts
cortical lesions, ssx specific in this area

diffuse white matter dz (Binswangers) -
numerous small subcortical lacunar infarcts in
periventricular regions
ssx will be diffuse since hitting many tracts

high risk:
stroke, age, htn, vascular dz, diabetes, smoking, lipidemia,
vestibulo-ocular reflex
keeps eyes stable while moving
slow movements away from rotation, nystagmus back in direction of movement to the midline

involves oculomotor, trochlear, and abducens

semicircular canal stimulation --> vestibular nerve --> vestibular nuclei brainstem --> MLF to nuclei of CN3, 4, 6 --> slow movements and nystagmus

warm water in one ear will simulate movement toward this ear (slow opposite, nystagmus towards), cold water will simulate movement away from this ear (slow towards, nystagmus opposite)
wernickes encephalopathy
common in alcoholics - thiamine (B1) deficiency from bad nutrition malabsorption --> periventricular hemorrhage, symmetric cerebral/brain stem/MAMMILLARY BODIES degeneration (think Papez circuit)
-->
ataxia, nystagmus, opthalmoplegia, anterograde amnesia

thiamine required for PDH, can't metabolize glucose, also cofactor of transketolase HMP shunt

glucose infusion makes it worse unless thiamine co-infused!

beri beri is thiamine deficiency secondary to malnutrition --> peripheral neuropathy, demyelination

can progress to Korsakoff syndrome = anterograde amnesia, confusion, apathy, lack of insight, confabulation
GSE, SVE, GVE, GVA, SVA, GSA, SSA
sensory only
CN1 - special sensory olfaction
CN2 - special sensory vision
CN8 - special sensory audition/vestibular

mostly somatic motor
CN3 - general somatic motor eyes (EW n.), GSA
proprio, general visceral motor parasymp ciliary m.
(accomodation) + pupil constrictor m.
CN4 - general somatic motor eyes, GSA proprio
CN6 - general somatic motor eyes, GSA proprio
CN12 - genereal somatic motor tongue, GSA proprio

brachial arch (visceral + somatic, general + special)
CN5 - special visceral motor mastication, GSA face
CN11 - special visceral/general somatic motor SCM
+trap, GSA proprio
CN7, 9, 10 - SVE, GVE, GVA, SVA, GSA
CN7 - parasymp lacrimation/submandibular/
sublingual saliva, special visceral motor face
expression, special visceral sensory tongue,
general somatic sensory behind ear
CN 9 - SVE stylopharyngeus, GVE parotid via otic
ganglion, GVA pharynx, SVA post 3rd tongue,
GVA carotid sinus body
CN10 - SVE pharynx/larynx/esophagus/uvula/
levator palate, GVE parasymp neck/thorax/abd
(to splenic flexure), GVA pharynx/larynx/esoph
trachea/thoracic/abd viscera (to splenic flexure)
nucleus solitarius
medulla

carotid+aortic (body) chemo + (sinus) baro receptors
chemo mostly senses O2, pH...some CO2

reflexes: carotid, aorta, gag, J-receptors cough, GI motility

carotid = glossopharyneal n.
aorta = vagus n.
nucleus ambiguus
rostral medulla, near inf. olive

CN10 motor for palate, esophagus, pharynx, larynx
CN10 parasymp for cardioinhibitory
vasomotor center
medulla

senses CO2, stimulates sympathetic drive by incr HR, and shunting blood to exercising muscle
reticular formation lesion
coma, LOC

controls conscious/unconscious states: sleep/awake/alert/attentive
blood supply to brainstem
basal ganglia circuit
cranial fossa CN exits
some key cranial arteries and veins other than the big cerebral arteries
othalmic a. - branch of the internal carotid, to eye via optic canal with CN2

anterior choroidal a. - branch of the internal carotid, perfuses choroid plexus, LGN, GPE, post. internal capsule

labyrinthine a. - branch of the basilar a., follows CN 7,8 to perfuse internal acoustic meatus/inner ear

superior/inferior sagittal, cavernous/petrosal, occipital sinuses
great cerebral vein, straight sinus, transverse sinus, sigmoid sinus, internal jugular vein
prefrontal areas and fxn
ortitofrontal - inhibition, emotion, drive, ADDICTION, planning, problem solving

medial - basal ganglia, motor

lateral - depression, mood, OCD, schizophrenia
medial temporal lobe - hippocampus + amygdala
hippocampal formation = hippocampus + dentate gyrus + subiculum

kluver-bucy syndrome = bilateral destruction of anterior temporal lobes --> docile, hyperorality, hypersexual

small amygdala/hippocampus with schizophrenia
proprioception
limb position + kinesthesia (movement) sense

muscle spindles - intrafusal, parallel to muscle, detect length/velocity of stretch

GTO - tendons, in series with muscle, detect tension and force of contraction/stretch
sympathetic chain
REMEMBER - everything sympathetic originates in hypothalamus --> intermediolateral nuclei in SC

gray rami at every level from postganglionic sympathetics

T1-L2
white rami - to chain and prevertebral ganglia
gray rami - from chain, postganglionics to spinal nerves, posterior

inside chain, key ganglia with postganglionics:
~C4-T2 (from T1-2 in cord) = cardiac

T1-T5 = lung bronchial tree

superior cervical ganglion = tarsal m, lacrimal
gland, pupil dilator, submandibular/lingual glands,
parotid, heart

every level from top cervical to bottom sacral =
blood vessels, errector pilli, sweat glands

splanchnic nerves to outside chain, prevertebral key plexus with postganglionics:
celiac plexus = stomach, duodenum
superior mesenteric plexus = SI and LI
inferior mesenteric plexus = sigmoid colon/rectum
vas deferens

preganglionic direct from cord/chain to adrenal medulla to stim chromaffin cell release of NE/E
parasympathetics
midbrain:
CN3 EW nucleus --> ciliary ganglion -->
pupil constrictor, ciliary body

pons:
CN7 lacrimal/superior salivatory n. -->
pterygopalatine/submandibular ganglia -->
lacrimal, submandibular/sublingual glands

medulla:
CN9 inferior salivatory n. --> otic ganglion -->
parotid gland
CN10 dorsal motor n. --> directly to heart,
bronchial tree, stomach, SI, LI

S2/3/4:
pelvic splanchnics --> sigmoid/rectum, bladder,
erectile tissue
axonal transport
anterograde - kinesin
fast: protein, NT
slow: NF, MTs

retrograde - dynein
GF receptors, pinocytosis, etc
think: tetanus toxin, polio virus, rabies virus, HSV
werdnig-hoffman SMA
infantile SMA
SMN1 mutation
loss of anterior horn LMNs
tabes dorsalis
tertiary syphilis, hits DCMLS
cerebrovascular regulation: O2, CO2
high CO2 - dilate
low CO2 - constrict
high O2 - constrict
low O2 - dilate
astrocyte fxns
BBB sensing
glutamate uptake at synapse
glucose uptake --> produce lactate --> transferred
to neurons --> converted to pyruvate
PET imaging
measures 2-deoxyglucose tracer, proxy for energy consumption/active brain regions
fMRI
detects magnetic signature of oxyHgb vs deoxyHgb in vasculature
ratio of oxy/deoxy indicates active brain regions
choroid plexus
projects into lateral, 3rd, 4th ventricles
infoldings of pia, covered by modified ciliated ependymal cells
tight junctions between cells maintain BBB
secretes CSF
biogenic amines info
low monoamines - depression

DA: measured as homovanillic acid in blood/CSF/UA
high in schizo, pos sx
low in PD
nigostriatal
inhibits PRL secretion

NE: measured as vanilllmandelic acid blood/CSF/UA
high in pheo
low MHPG in suicide
DA hydroxylase converts to NE
locus ceruleus
SNRI

5HT:
low in depression, suicide, aggressive/violent, impulsive, Tourettes, alcohol, bulimia
mood, sleep, sex, impulse control
tryptophan (tryptophan hydroxylase) --> 5HT
raphae nucleus
SSRI, SNRI

histamine:
blocked histamine - sedation, incr appetite

AcCh:
low levels - Alz, Downs, movement/sleep dz
AcCOA + choline = AcCh
AcChE --> choline + acetate, choline reuptake
nucleus basalis produces
block to delay progression of Alz (donepezil, rivastigmine, galantamine)
block mAcChR (antipsychotics, antidepressants) -->
dry mouth, blurry vision, urinary retention,
constipation
AA NTs
glutamate:
associated with epilepsy, schizo, neurodegenerative
non-essential AA, made from alphaketoglutarate
receptors: AMPAR; NMDAR+kainate - LTP

GABA:
from glutamate, via glutamate decarboxylase
uptake at syn by GABA transaminase
antianxiety - benzo and barbs incr Cl conductance

glycine:
regulates glutamate activity
neuropeptides
endogenous opiods - enkephalins, endorphins
decr pain, possibly mediates placebo effect

blocked by naloxone

CCK - schizo
somatostatin, subP, ADH, oxytocin, VIP - mood dz
circadian rhythms, sleep
sleep, wake, temp, hormones
hypothalamus, suprachiasmatic n. clock

LACK OF SLEEP can lead to PSYCHOSIS
EEG, sleep, seizures, comas
pyramidal neurons, synchrony = amplitude, controlled by mutual excitation/inhibition and thalamic gain

FREQUENCY associated with sleep vs wake, seizure, coma
faster = more alert, fastest are BETA
slower = less alert, slowest are DELTA = coma

SEIZURES = HIGH amplitude LOW frequency synchronous firing
decr by GABA (benzo)
decr by less excitability (carbamazipine, phenytoin)

sleep - normal is 90% time in bed spent sleeping
REM = beta + alpha waves, incr P/BP/R
high brain activity
~90min latency normal
stage 1 = theta, decr P/BP/R
stage 2 = LARGEST %sleep, sleep spindles/K complex
stage 3/4 = slow delta, deep sleep

sedatives decr REM and delta sleep
sleep disorders
dyssomnia - problems in timing, quality, amount of sleep
sleep apnea, narcolepsy, hypersomnia

parasomnia - abnormal physiology/sleep behavior
bruxism (grind teeth), sleepwalk, night terrors,
restless leg

insomnia:
associated with MDD - waking too early
bipolar - decr sleep with mania
anxious, CNS stimulants, sedative withdrawl, pain
tx with avoid caffeine, low dose benzo

narcolepsy:
sleep attacks, low nighttime REM
hallucinations before falling asleep
cataplexy/sleep paralysis
tx with stimulants = MODAFENIL (non-amphetamine stimulant, less s/e than amphetamines, first line)
acute pyogenic bacterial meningitis
if parenchyma also involved = meningoencephalitis

ssx: fever, ha, photophobia, irritable, AMS, neck stiff
Kernig sign: cant extend knee when hip flexed
Brudzinski sign: flex neck --> flex hips/knees

CSF - cloudy, incr opening pressure, PMN, high protein low glucose
aseptic/viral meningitis
self limiting and tx symptomatic
ENTEROVIRUS
CSF: high lymphocytes, mild protein, normal glucose
chronic meningitis
TB
ha, general malaise, confusion, emesis
CSF: high lymphocytes/PMN, very high PROTEIN, normal glucose
fibrinous exudate --> can lead to hydrocephalus
brain abscess
direct extension - mastoiditis
hematogenous - endocarditis

focal neuro deficits depending on location
incr ICP, herniation
concussion
rapid change in momentum

LOC, temp resp arrest, loss of DTRs
think epidural hematoma
diffuse axon injury/white matter path
axon swelling, punctate hemorrhages

uncal herniation --> blown pupil
from compression of parasymp fibers CN3
antidepressants in general
SSRI, SNRI
inhibit reuptake of NE, 5HT
...but ultimately downregulate post syn receptors
take weeks to work
also have anticholinergic effects
interact with histamine - weight gain and sedation
cardio effects - othostatic
overall fewer s/e

can precipitate a manic episode in borderline bipolar pt

MAOI
for atypical depression
fatal rxn with tyramine and ephedrine/
sympathomimetics --> incr TYRAMINE --> hypertensive crisis, stroke
seratonin syndrome in combo with SSRI
mood stabilizers in general
to PREVENT manic/depressive episodes in bipolar
lots of s/e:
ebstiens, hypothyroid, tremor, renal fail/SIADH, GI, blunting
weeks to work

anticonvulsants
carbamazepine, valproate, gabapentin, lamotrigine, topiramate
decr neuron excitability by decr ion channel conduct
also tx for bipolar, especially rapid cycling type
s/e: aplastic anemia, agranulocytosis
neural tube, alopecia
antianxiety/antihypertensive/anesthetics in general
benzo - bind GABA-A, incr Cl conductance
sedation
s/e: seizure at high dose
tolerance/dependent potential
flumazenil - antidote (benzo-R antagonist)

buspirone - nonbenzo antianxiety, for chronic/generalized anxiety disorder
nonsedating, no dependence/abuse/withdrawl

beta blockers used to help with benzo withdrawl
stimulants in general
amphetamines - used for depression, narcolepsy, ADHD
addiction potential
modafanil for narcolepsy
specific neuropsych drugs
dementia:
AcChE inhibs (tacrine, donepezil, rivastigmine)
memantin - blocks NMDAR

addiction:
alcoholism: disulfiram, naloxone/naltrexone
opiods: methadone, buprenorphine - decr
withdrawl

stroke: NSAIDs, thrombolytics (streptokinase)

MS: steroids (prednisone), beta IFN, baclofen for contractures, cholinergics to help empty bladder

PD: DA agonists, anti-cholinergics
amantidine, trihexyphednidyl (antiAcCh),
bromocriptine, levodopa, carbidopa
pigments and inclusions
lipofuscin - aging, cytoplasmic
melanin - substantia nigra, lost in PD
lewy bodies - PD
negri bodies - rabies, pyramidal and purkinje
hirano bodies - hippocampus, Alz
neurofibrillary tangles - cytoplasmic, Alz
Cowdry type A inclusions - HSV
neurodevelopment, embryo
neural plate ectoderm, notocord in mesoderm -->
neural tube
(brainstem and SC) --> alar plate: sensory, basal
plate: motor
neural crest --> PNS = peripheral nerves,
sensory/autonomic ganlgia
(DRG, schwann, ganglia, leptomeninges,
chromaffin, melanocytes, teeth blasts, AP
septum, parafollicular C cells, skeletal + CT of
pharyngeal arches

anterior neuropore = lamina terminalis
fail to close = anencephaly
posterior neuropore
fail to close = spina bifida, look for leg malformed
occulta - hairs, dura outside column
meningocele - dura, subarachnoid outside
meningomyelocele - whole cord outside
rachischisis - no cord, just neuroectoderm on back

three primary vesicles, 5 secondary -
forebrain:
telencephalon - hemispheres, ventricles
diencephalon - thalamus, third venticle
midbrain:
mesencephalon - midbrain, cerebral aqueduct
hindbrain:
metencephalon - pons, cerebellum, upper 4th ventr
myelencephalon - medulla, lower 4th ventricle

myelination - 4th month of gestation, CST not fully myelinated until 2yo, CTX not done until 30s
oligodendrocytes CNS (NOT retina)

SC conus medullaris at L3 in newborn, L1 in adult

CN2 from diencephalon, in choroid fissure
fail to close = coloboma iridis

adenohypophysis - ectoderm diverticulum of primitive mouth stomodeum - Rathke's pouch
craniopharyngioma - hypopit in children
neurohypophysis - neural tube derived

cranium bifidum - occipital bone defect, brain hernia
arnold chiari malformation - elongation cerebellar
tonsil through foramen magnum, hydrocephalus
dandy walker malformation - enormous dilation of
4th ventricle, posterior fossa cyst, from failure of
Magende and Luschka to open, occipital
meningocele, unformed vermis, elevation collosum
splenium
fetal alcohol syndrome - mental retardation,
microcephaly, congenital heart dz, possible
holoprosencephaly
holoprosencephaly - seen in trisomy 13, no
hemispheres, sometimes no collosum...can happen
in fetal alcohol syndrome
hydranencephaly - bilateral hemisphere infarct,
occlusion of carotids, dilated ventricles
MRI weights
T1 - fat bright
T2 - water bright
posterior communicating artery aneurysm hits
CN3 --> palsy
anterior choroidal a perfuses
LGN, GP, posterior limb internal capsule
anterior communicating artery aneurysm hits
CN2 --> bitemporal lower quadrantanopia
striate arteries
perfuse lentiform nuclei

anterior cerebral --> medial striate --> putamen/caudate/internal capsule

middle cerebral --> lateral striate --> internal capsule/caudate/putamen/GP
major blood supply to pons, midbrain, thalamus
pons - basilar
midbrain - posterior cerebral
thalamus - posterior cerebral
posterior cerebral a. occulsion visual field deficit
contralateral hemianopia with macular sparing
subdural hematoma is laceration of
superior cerebral bridging veins
middle meningeal artery
branch of maxillary a, enters cranium via foramen spinosum

supplies most of the dura --> laceration = epidural hematoma
cranial nerves with parasympathetic components
CN3 - ciliary ganglion (pupil constrictors, ciliary
body)
CN7 - pterygopalatine and submandibular ganglia
(lacrimal, nasal, palate glands)
CN9 - otic ganglion (parotid)
CN10 - terminal/intramural ganglion
autonomic system dz
hirschprungs dz - megacolon, neural crest migration fail for myenteric plexus

familial dysautonomia - JEWISH, AR, sweating, orthostatic, trouble feeding bc decr gastric motility, progressive sensory loss, loss of neurons in autonomic/sensory ganglia

raynauds - terminal arteries in extremities, cyanosis, peripheral constriction...tx with preganglionic sympathectomy

peptic ulcer dz - incr parasymp tone

horners - oculosympathetic paralysis

shy drager syndrome - intermediolateral nuclei loss, othostatic, anhidrosis, impotence, bladder atonicity

botulism - clostridium botulinum, paralysis of striated muscle + dry eyes, mouth, orthostatic, ahidrosis, impotence, bladder atonicity

lambert eaton myasthenic syndrome - NMJ presynaptic cant release AcCh, with dry mouth, proximal muscle weak, abnormal DTRs
projections from superior cervical sympathetic ganglion
- via external carotid to face vessels, glands, skin
- via superior orbital fissure, long ciliary n., pupil
dilator
- via optic canal to levator palpebrae
location of the substantia nigra
between red nucleus and cerebral crus in midbrain
facial nerve branches
superior salivatory/SVE motor n pons, solitary n medulla --> geniculate ganglion via inner auditory meatus -->

chorda tympani n. --> lingual n --> submandibular/sublingual glands, sensory tongue

greater petrosal n --> nasal/palatine/lacrimal gland
contents of the cavernous sinus
internal carotid a.
CN 3,4,V1,V2,6
postganglionic sympathetics to eye
auditory system is derived from
suface ectoderm --> otic placode
organ of Corti hair cells innervated by the spiral ganglion

inner hair cells - chief sensory, 90% of cochlear n., single row

outer hair cells - thresholding, 10% cochlear n., three rows

CN8 enters brainstem at cerebellopontine angle, innervates SUPERIOR olivary n. and cochlear n.

projections from superior olive/cochlear n. decussate at TRAPEZOID body --> lateral lemniscus --> MGN thalamus --> gyrus of Heschl
vestibular sx projections
semicircular canals, utricle, saccule --> vestibular division of CN8 --> vestibular n. + flocconodular cerebellum --> MLF --> abducens, trochlear, occulomotor n. + lateral vestibulospinal tract SC
cerebellopontine angle tumors
SAME:
schwannoma, arachnoid cyst, meningioma, ependymoma/epidermoid
lacunar infarcts
small cavities, can happen all over brain (BG, internal capsule, pons, cerebellum)

occlusion of small PENETRATING arteries
etiology: CHRONIC HTN, DIABETES

LIPOHYALINOSIS = destroyed vessel, foam cells, necrosis

MICROATHEROMAS = lipid laden macrophages in vessel
drugs of abuse
PCP - phenylcyclidine:
hallucinogen, inhibits NMDARs
detachment, distance, slurred speech, ataxia, involuntary movements, exaggerated gait, nystagmus, paranoia, aggression...can look like shizophrenia

heroin - opiate
intense euphoria, constricted pupils, lethargy, clammy skin, nausea

amphetamine - sympathomimetic
like NE, for depression and ADHD
rapid HR, incr BP, anxious, sweating, tremor, dry mouth, hallucinations

cocaine - NE/DA/5HT reuptake inhib
rapid HR, high BP, blurry vision, tremor, twitching, CP, irritability, hallucinations, delusions

diazepam - benzo
binds GABA-A, allosterically incr GABAR*
mild euphoria, relaxation, confusion, amnesia, sedation, slurred speech, low BP, low HR

LSD - lysergic acid, hallucinogen
5HT-R agonist
dilated pupils, tremor, confusion, sweating, disorientation, incr HR, HALLUCINATIONS

marijuana - cannabinoid, THC
stimulates cannabinoid-Rs
syringomyelia
central cystic dilation in cervical SC (syrinx) slowly enlarges in C8-T1
damages ventral white commissure and anterior horns

spinothalamic tract and LMN ssx typically C8-T1...in advanced can cause UMN signs in lower extremities hitting lateral tracts
reserpine
old drug for htn, not really used except in poor countries
inhibits storage of adrenergics in vesicles
so basically sympathectomy
also can cause depression bc INHIBITS THE STORAGE OF BIOGENIC AMINES INTO VESICLES
the first area of the brain damaged during global cerebral ischemia
HIPPOCAMPUS
muscarinic AcCh effects on endothelium
cholinomimetics promote release of NO aka endothelium derived relaxing factor (EDRF)

NO --> guanyl cyclase --> cGMP --> Ca efflux --> relaxation of SM
malignant hyperthermia
anesthetic, esp halothane, and succinylcholine sensitivity

AD, Ca/RyR in sarcoplasmic reticulum
instead of releasing small amounts of Ca
in response to stim, releases large
amounts in SKELETAL MUSCLE
--> excess Ca --> ATP consumption --> heat generation --> hyperthermia, rhabdomyolysis with K, myoglobin, and CK release, muscle rigidity, tachy

HAPPENS SHORTLY AFTER SURGERY WITH ANESTHESIA

tx: Dantrolene - inhibs Ca release via RyR
fragile X syndrome
FMRR1 is on long arm of chrX, CGG repeat expansion > 200 repeats
results in hypermethylation of FMR1 and gene inactivation

ssx: mild-severe MR, long thin face, prominent forehead+jaw, macroorchidism post puberty, large protruding ears, tooth crowding, arched palate
chromosomal instability do's
DNA repair enzyme defects
xeroderma pigmentosum, ataxia-telangiectasia, Fanconi anemia, Bloom syndrome, Lynch HNPCC
measles and the brain
helical, enveloped RNA virus
paramyxoviridae family

ssx: fever, cough, coryza (runny nose), conjunctivitis, erythematous maculopapular rash

complications:
SUBACUTE SCLEROSING PANENCEPHALITIS
pneumonia, secondary bacterial infections (pneumonia, acute otitis)

subacute sclerosing panencephalitis happens several years after recovery, likely from measles virus MISSING M ANTIGEN, failure of virus clearance by immune sx -->encephalitis
inflammation, demyelination, gliosis
INTRANUCLEAR INCLUSIONS
deficits, dementia, fatal
high measles IgG
NO Ab AGAINST M PROTEIN however
oral thrush + multiple ring enhancing lesions in brain + seizures and lymphadenopathy in HIV pt
toxoplasmosis
from cat feces
tx:
zolipidem
short acting hypnotic, UNRELATED TO BENZOs chemically, but LOWER RISK OF DEPENDENCE/TOLERANCE
mini mental status exam
orientation - name, location date
comprehension - multistep command
concentration - recite months backwards
short term memory - 3 words, 5mins
long term memory - details of life event
language - write sensible sentence
visuospatial - draw CLOCK FACE
mAcChR activity

Flickr Creative Commons Images

Some images used in this set are licensed under the Creative Commons through Flickr.com.
Click to see the original works with their full license.