1
Q
cells of the brain
A
neural tube is finished by day 19 -21 (FA), 28-29 days (Goljan)
- point first 2-3 weeks
CNS:
neurons - Nissl bodies in dendrites and cell bodies
-injury –> Wallerian degeneration - axon degenerates distally, retracts proximally
-regeneration occurs in PNS
- chromatolysis aka axonal reaction - reaction of neuronal cell body in response to axonal injury –> increased protein synthesis, displacement of nucleus to periphery, dispersion of Nissl bodies, round cellular swelling
Peripheral NS:
- Schwann cells sense axonal degeneration and quickly being to degrade myelin and secrete cytokines that recruit macrophages –> myelin debris is cleared quickly
- in CNS - BBB means that microglia are recruited more slowly –> extremely slow removal of myelin debris, years!
- axonal growth is suppressed via myelin-associated inhibitory factors and astrocyte produced glial scar (ahead of where the neuron could regenerate)
astrocytes - extracellular K+ buffer, remove excess neurotransmitter, BBB, glycogen fuel reserve, reactive gliosis
- neuroectoderm
- GFAP
mesoderm –> microglia ~ macrophages
- not readily discernible by Nissl stain
- HIV-infected microglia fuse –> multinucleated giant cells
Schwann cells - 1 neuron, GBS
oligodendrocytes - many neurons, neuroectoderm (so fried-egg appearance on histology)
-injured in MS, PML, and the leukodystrophies
-but in MS - antibodies against myelin sheath
-in PML - oligodendrocyte is damaged
2
Q
spina bifida occulta
A
dura is intact
associated with tuft of hair/skin dimple
3
Q
holoprosencephaly
A
failure of hemispheres to separate
- sonic hedgehog pathway mutations, trisomy 13, and fetal alcohol syndrome
cleft lip/palate
cyclopia
4
Q
posterior fossa malformations
A
Chiari 1 - ectopic cerebellar tonsils
- asymptomatic kid, adults with headaches and cerebellar symptoms
- associated with syringomyelia
- syringomyelia - can extend into anterior horns and further –> host of symptoms including DCML affected, UMNs affected, scoliosis due to paresis of paravertebral muscles
Chari 2
- herniation of vermis and tonsils
- aqueductal stenosis
- associated with meningomyelocele
Dandy-Walker - failure of cerebellar vermis to form –> absent cerebellum
- cystic enlargement of 4th ventricle, non-communicating hydrocephalus
- congenital aqueductal stenosis – hydrocephalus because the sutures havent fused
- in an adult - ventricles would dilate and you would have normal pressure hydrocephalus - associated with spina bifida
5
Q
polio
A
fecal-oral transmission
damages anterior motor horn (LMN damage) –> asymmetric flaccid paralysis, hyporeflexia
v.s. Werdnig-Hoffmann disease - AR, inherited degeneration of anterior motor horn –> floppy baby
6
Q
ALS
A
UMN and LMN disorder
-LCST and anterior horn affected
Zn-Cu SOD mutations associated with familial cases
fatal, treat with riluzole (decreases glutamate excitotoxicity)
7
Q
Friedreich ataxia
A
AR, GAA repeat in frataxin gene
- controls Fe regulation in mitochondria –> increased free radical damage
- cerebellum and multiple spinal cord tracts are damaged
staggering gait, frequent falls, kyphoscoliosis, HCM (cause of death)
8
Q
meningitis bugs
A
neonates - GBS (can also cause sepsis in newborn, premature rupture of membranes –> chorioamnionitis –> fetal sepsis), E coli, Listeria (pregnant women should NOT eat soft cheeses, tumbling motility)
- Listeria is a gram positive rod
- Trichomonas also has tumbling motility
kids/teens - N. meningitidis, enters through nasopharynx
adults/elderly - S. pneumo (gram pos diplococci)
- S. pneumo - alcoholics, asplenics
non-vaccinated infants - H. flu (gram negative coccobacilli)
- vax against capsule
Coxsackie virus - most common viral cause
-photophobia esp with viral etiology
fungi in immunocompromised
-CSF - lymphocytes and low CSF glucose
S aureus following neurosurg
treat with antibiotics and steroids (prevents scar tissue formation and obstructive hydrocephalus)
- sensory deafness is a common complication of meningitis
(v.s. encephalitis - MSE changes, sleepy)
9
Q
watershed areas
A
areas between ACA/MCA and MCA/PCA
damage occurs due to severe hypotension
upper leg/upper arm weakness and defects in higher order visual processing
10
Q
global cerebral ischemia
A
mild - insulinoma (hypoglycemia), transient confusion with quick recovery
moderate - infarcts (shock, hypotension, anemia) in watershed areas
- damage to pyramidal neurons of cortex (layers 3, 5, 6) –> cortical laminar necrosis
- pyramidal neurons of hippocampus, vulnerable hippos
- Purkinje layer of cerebellum
severe - diffuse necrosis of brain –> vegetative/death
11
Q
focal ischemia
A
thrombotic - pale, wedge (occurs at branch points of arteries), periphery of cortex
emboli - hemorrhagic infarct, periphery of cortex, usu involves MCA
hypoxic - common during CV surgeries, affects watershed areas
lacunar - secondary to hyaline arteriolosclerosis
- tiny infarcts, which are reabsorbed –> lacuna
- lenticulostriate vessels (off MCA) are most affected
- depending on the part of the brain - you can have pure sensory (thalamus) or pure motor infarcts (internal capsule)
ischemia –> pale infarct –> liquefactive necrosis
1) 12-24 hrs - red neurons, pyknotic nuclei
2) 1d-1w - neutrophils, microglia
3) 1w-1mo - reactive gliosis + vascular proliferation
4) cyst lined by astrocytes = glial scar
ischemic stroke can cause vascular dementia - encephalomalacia
12
Q
intracerebral hemorrhage
A
most commonly due to Charcot-Bouchard microaneurysms - complication of HTN
basal ganglia
- not visible on angiography
- hemorrhage would appear as a hyperdensity on CT
aneurysmal rupture –> blood clot
sympatholytics - methyldopa and clonidine stimulate a2 receptors
- can be use intracranial hemorrhages caused by HTN
13
Q
SAH
A
rupture of berry/sacular aneurysm - lacks media layer at the branch point
- most commonly located in anterior circle of Willis
- will see bleed on the bottom of the brain
- usually at branch of ACA –> will compress optic chiasm
- if PCA is involved –> oculomotor nerve compression
- seen in Ehlers-Danlos, ADPKD
remember - Struge-Weber has port-wine stain and AV malformation on that same side of the brain
- interestingly - only 10% SAH is due to AVM
- AVMs cause intraparenchymal bleeding
4-10 days after hemorrhage –> vasospasm (due to blood clot breakdown or rebleed) –> ischemic infarct
-use nimodipine
14
Q
epidural hematoma
A
talk-and-die syndrome
- uncal herniation - CN3 palsy
subdural hematoma - bridging vein rupture, waxing/waning consciousness (?)
CT to visualize blood (MRI is no good)
15
Q
herniation
A
tonsilar herniation - compresses brainstem –> cardiopulmonary arrest
subfalcine herniation - ACA compression, infarct
uncal herniation - CN3 compression –> eyes down and out, pupils dilated (PSNS tone is lost)
-can compress PCA - infarction of occipital lobe
(-pulls paramedian artery - duret hemorrhages on brain stem) Pathoma
- (FA) compresses contralateral crus cerebri at Kernohan notch —> ipsilateral paresis
transtentorial –> caudal displacement of brain stem –> Duret hemorrhages, fatal
16
Q
strokes by artery
A
MCA - contralateral hemiparesis and hemisensory loss of face and upper limb
- lower limbs are spared/minimally affected
- Wernicke’s + right superior quadrant visual field defect
- Brocas - aphasia (left), hemineglect (right)
- can have gaze and visual field disturbances
ACA - contralateral hemiplegia lower limb
- bilateral ACA occlusion –> behavior symptoms, primitive reflexes, urinary incontinence
lenticulostriate artery - contralateral paralysis and sensory loss of face and body
cerebellar arteries: ipsilateral horner and decreased pain and temp from face
-decreased pain and temp from contralateral body
posterior inferior cerebellar - lateral medulla
-dysphagia, hoarseness, and decreased gag reflex
anterior inferior cerebellar - lateral pons and facial nucleus
- ipsilateral facial paralysis - facial nucleus
- ipsilateral pain and temp loss of face (trigeminal nucleus) and contralateral loss of pain/temp in extremities (ALT)
- ipsilateral hearing loss
- cerebellar dysfunction
basilar - damage to base of the pons (corticobulbar and corticospinal tracts, paramedian tegmentum)
- locked in syndrome (but also loss of horizontal eye movements)
PCA - occipital lobe, contralateral hemianopia with macular sparing
if there is no hemorrhage - pt is a candidate for tPA
17
Q
leukodystrophies
A
lysosomal storage, etc. disorders
metachromatic leukodystrophy - arylsulfatase, myelin cant be degraded and accumulates in lysosomes
-central and peripheral demyelination
Krabbe disease - galactocerebroside acc in macrophages –> destruction of myelin sheath
-peripheral neuropathy, developmental delay, optic atrophy
adrenoleukodystrophy - impaired metabolism of FAs –> FAs acc in adrenals, white matter, and testes
18
Q
MS
A
HLA-DR2
T cells abnormally react to myelin –> release IFNy –> call in other WBCs
optic neuritis = monocular vision loss, pain on eye movement, Marcus Gunn pupil
Lhermitte phenomen
symptoms exacerbate with increased body temp
treat
- high dose IV steroids during acute attack
- INFb slows disease progression, can use glatiramer, natalizumab
treat symptoms
- neurogenic bladder - catheterization, antimuscarinic antagonists
- spasticity - baclofen, GABA-B receptor agonists
- pain - TCAs, anticonvulsants
19
Q
Progressive multifocal leukoencephalopathy
A
latent JC virus reactivation –> destruction of oligodendrocytes
rapidly progressive neuro signs –> death
20
Q
osmotic demyelination
A
central pontine demyelination
= locked in syndrome (anything with the pons will lead to locked-in syndrome)
21
Q
Picks disease
A
frontotemporal dementia
- behavioral variant or primary progressive dementia variant
- may have associated movement disorders
round aggregates intracytoplasmic inclusions of tau protein - seen on silver stain
22
Q
Parkinson’s
A
normally: cortex –> BG –> cortex
- D1 receptors on striatum increase stimulation of cortex
- D2 receptors on striatum decrease inhibition of cortex
- Parkinsons - loss of dopamine, excess cholinergic activity
features
- contain Lewy bodies - a-synuclein, eosinophilic
- later onset dementia
- MPTP - contaminant in illegal drugs can cause parkinsonian symptoms
- why? - because MPTP is metabolized into a toxic metabolite by MAO-B
- defects in ubiquitin-proteasome system have also been implicated in parkinsons
drugs = BALSA
- dopamine agonists - bromocriptine (ergot), *pramipexole, *ropinirole
- increases dopamine availability - amantidine (increases released, decreases uptake) –> tox - anticholinergic effects, ataxia, livedo reticularis (lace-like mottled skin)
- increases L-dopa availability -levidopa/carbidopa (carbidopa inhibits DOPA decarboxylase, peripheral dopamine causes N&V)
- levidopa - absorbed in SI by neutral-AA transporter
- levidopa adverse effects - arrhythmias (due to increased peripheral catecholamines), on-off (dyskinesia-akinesia) will long-term use
- why do you get on-off symptoms - as PD progresses, therapeutic window for levidopa narrows (possibly due to nigrostriatal degeneration). Small changes in serum drug levels (as occurs between doses) leads to motor fluctuations - pergolide - D2 agonist
- entacapone, tolcapone - prevent peripheral L-DOPA degradation, inhibit peripheral COMT
- can add entacapone for pts who are experiencing wearing-off periods in between doses - prevent dopamine breakdown - selegine (MAO-B inhibitor), tolcapone (inhibits central COMT)
- curb excess cholingeric activity - benztroptine, trihexyphenidyl
clinical note: many neurologists use selegiline, anticholinergics, and amantadine
- levidopa/carbidopa are secondary option
VS Lewy body dementia - where dementia is early onset (dementia and hallucinations) –> then progresses to parkinsonian features
23
Q
Huntington’s
A
gain-of-function mutation - mutated huntingtin gene –> increased histone deacetylation –> histone and DNA interact more tightly –> unable to transcribe neutrophic factors
degeneration of GABAergic neurons in CAUDATE nucleus and Ach neurons
increased dopamine in brain
tetrabenazine and reserpine - inhibit VMAT (vesicle monoamine transporter) –> decreased dopamine vesicle packaging and release
haloperidol - D2 antagonist
24
Q
normal pressure hydrocephalus
A
wet, wacky, wobbly
- magnetic gait
- frontal lobe - inhibits bladder contractions
due to decreased CSF resorption
- idiopathic, secondary to brain trauma or SAH
25
Childhood CNS tumors
kids - BELOW tentorium
*pilocytic astrocytoma - benign, cerebellum, astrocytes with thick eosinophilic processes (Rosenthal fibers), GFAP pos
ependymoma - malignant, perivascular pseudo-rosettes, rod shaped bodies found near nucleus
- most commonly in 4th ventricle
medulloblastoma - neuroectoderm (granular cells of cerebellum), malignant
- small, round blue cells + homer-Wright rosettes
- mets via CSF, drop mets on SC
craniopharyngioma - epithelial remnants of Rathke's pouch
- nests of squamous epithelium with wet keratin in the center
- supratentorial
- optic chiasm compression
- recurrent
- calcifications on imaging
pinealoma - Parinaud syndrome
1) vertical gaze palsy - compression of tectum
2) obstructive hydrocephalus
3) precocious puberty - bHCG production
26
adult CNS tumors
Glioblastoma multiforme - grade 4 astrocytoma
- cerebral hemispheres, crosses corpus callosum
- GFAP pos
- pseudopalisading necrosis - necrosis surrounded by an edge of viable cells
oligodendroglioma
- calcified, fried-egg cells, chicken-wire capillaries
- frontal lobe - may present with seizures
meningioma - benign, females (tumor expresses estrogen receptor), arachnoid cell origin
- found in cerebral convexities, dural tail
- whorled cells --> which can calcify to form psammoma bodies
- seizures
schwannoma - CN8, internal acoustic meatus, CPA
- bilateral in NF2
- S100 positive
- cells arranged around eosinophilic cores
hem-angio-blastoma
- hemangio +retinal angioma = VHL
- can produce EPO
27
conjunctivitis
most commonly due to adenovirus
| swollen periauricular node
28
refractive errors + glasses
hyperopia - farsighted, eye too short --> light focuses behind retina, correct with convex/converging lens
v.s. myopia
astigmatism - abnormal curvature of cornea
presbyopia - impaired accomodation
constantly having to change glasses - sorbitol is accumulating in lens and changing the refractive index of the lens
29
cataracts
acquired: ...alcoholic, smoker, prolonged corticosteroid use
congenital: ... trisomies, TORCHeS, Marfan, Alport, NF2, myotonic dystrophy
30
aqueous humor pathway
```
trabecular outflow (90%) --> episcleral vasculature
-increased with M3 agonist
```
uveoscleral outflow - increased with PG agonist
31
glaucoma
optic disc atrophy with thinning of outer rim of optic nerve head (aka cupping) - white/bright part of the optic disc looks larger
open-angle - increased age, AA, FH
- painless
- primary or secondary (blocked tracbecular meshwork due to WBCs from uveitis, RBCs form vitreous hemorrhage, retinal elements from retinal detachment)
closed-angle aka narrow = problems in iris lead to downstream problems
- primary - forward movement of lens against iris --> obstruction of aq humor flow through pupil --> fluid builds up behind iris --> pushes peripheral iris against cornea --> blocking flow through trabecular meshwork
- secondary - hypoxia from retinal disease --> vasoproliferation in iris
- chronic closure - asymptomatic but damage to optic nerve and peripheral vision
- acute closure - EMERGENCY, increased IOP pressures iris fwd... --> very painful, red eye. Sudden vision loss, halos around lights, frontal headache, fixed + mid-dilated pupil. DONT give epi because it dilates pupil.
Drugs:
a agonists - epi (a1), brimonidine (a2) - decreases aq humor synthesis
- foreign body sensation, redness
b-blockers - decrease aq humor synthesis, no vision changes
diuretics - acetazolamide (decreased humor synthesis), no vision changes
cholinomimetics (M3) - pilocarpine, carbachol, physostigmine, echothiophate - increased outflow via contraction of ciliary muscle and opening of trabecular meshwork
bimatoprost, latanoprost (PGF2) - increased outflow through uveoscleral pathway
- darkens color of iris and increases eyelash growth
32
uveitis
all layers of eye include the choroid, ciliary body, and iris (past the cornea)
associated with systemic inflammatory disorders
33
age-related macular degeneration
dry (80%) -deposition of yellowish material with gradual decrease in vision (Drusen)
- subretinal inflammation and abnormal ECM proliferation --> hypoxia (--> stimulates local VEGF)
-prevent with multivitamin and antioxidant supplements (disease is due to chronic oxidative damage), stop smoking
= GRADUAL
wet (exudative) - RAPID loss of vision due to bleeding (after neovascularization of choroid)
-pt will have metamorphopsia - distortion of straight lines
-anti-VEGF injections -
ranibizumab
34
diabetic retinopathy
nonproliferative - damaged capillaries leak blood --> hemorrhages and macular edema
-treat with blood sugar control
proliferative - chronic hypoxia --> vessel proliferation --> traction on retina
-treat with peripheral retinal photocoagulation, surgery, anti-VEGF
35
retinal detachment
retina separates from pigmented epithelium --> degeneration of photoreceptors --> vision loss
breaks are more common in pts with high myopia and/or history of head trauma
often preceded by posterior vitreous detachment --> retinal detachment --> monocular vision loss
surgical emergency
36
central retinal artery occlusion
retinal artery
37
retinitis
retinitis
CMV, HSV, VZV, etc.
- retinal edema and necrosis
v. s. retinitis pigmentosa
- inherited retinal degeneration
- painless, progressive vision loss - starts with night
- blindness (rods are affected first)
- bone spicule-shaped deposits around macula - black dots
38
Horner syndrome
```
PAM is horny
associated with lesion of SC above T1
-Brown-Sequard syndrome
-synringomyelia
-Pancoast tumor aka superior sulcus tumor- stellate ganglion alongside SC
```
thalamus --> synapse in lateral horn --> superior cervical ganglion (C2) --> sweat glands, smooth muscle of eyelid, pupillary dilator
39
CN4
innervates SO
CN6 - LR
CN3- rest
- PSNS fibers are on the periphery of CN3 - compression is more likely to cause mydriasis as opposed to ischemia (ex DM)
40
BBB
astrocyte foot processes - BM - tight junctions between capillary endothelium
area postrema
OVLT - osmotic sensing
neurohypophysis
vasogenic edema if endothelial tight junctions are destroyed
41
CSF
glucose can be consumed by cancer cells too
Cl- higher in CSF - 120
Mg is also higher
scenario: orbital fracture --> fluid drip
- what fluid is dripping out? - check Cl-
aqueductal stenosis - most common cause of hydrocephalus in kids
valsalva --> venous --> dural sinuses --> CSF --> will flow easily out of needle during LP = tells if entire subarachnoid space is patent
- dont hold your breath during exercise - disk will herniate due to pressure of CSF
hydrocephalus - meningitis due to TB at base of brain --> scar tissue --> blocked foramens of L and M
42
battle sign
basilar skull fracture, posterior fossa
43
dementia
1) neurodegeneration
2) cognitive deficit
3) loss of function
44
PB poisoning
papilledema - due to increased vessel permeability
due to ....acid (?)
45
essential tremor
most commonly diagnosed movement disorder - AD
worsens when holding object (v.s. Parkinsons - these folks have a resting tremor)
symptoms improve with alcohol consumption
treat with propanolol - b1/b2 blocker has CNS effects
46
tuberous sclerosis
AD - late manifestations
hamartomas
- tubercles/hamartomas that bulge into ventricles - hamartomas of astrocytes
- angiomyolipomas
- cardiac tumors - rhabdomyomas
mental retardation
Shagreens patches - hypopigmented patches that are hard to see, use Wood's light
47
NF
AD - late manifestations
cafe au lait spot, axillary freckling, acoustic neuroma, meningioma, *optic glioma (benign)
plexiform neurofibromas - benign tumor of peripheral nerve
pheochromocytoma - pt presents with HT
48
CMV
most common congenital infection - culture fetal urine
| periventricular calcifications
49
pig herder
taenia, cysticercosis --> seizures
50
barbiturates, benzos
barbs - GABA_A
- sedative, induction of anesthesia (thiopental)
INDUCES CYP450
- overdose treatment is supportive - assist respiration and maintain BP
benzos -pams, chlodiazepoxide, GABA_A
- uses - obvious, night terrors, sleepwalking, general anesthetic, hypnotic
- decrease REM sleep
- ATOM are short-acting - have higher addictive potential
- OTL metabolized outside the liver
- antidote - flumazenil (competitive antagonist)
alcohol also binds to GABA receptor
51
insomnia drugs
nonbenzo hypnotics:
ZZZ - zolpidem, zaleplon, esZopiclone
- act via BZ1 subtype of GABA receptor
- short duration - rapidly metabolized by liver
- decreased dependence risk
- sleep cycle less affected - compared to benzos
- antidote - flumazenil
suvorexant - orexin (hypocretin) receptor antagonist
- orexin involved in wakefulness and appetite, deficiency leads to narcolepsy
- no dependence
- ADRs - abnormal dreams, URI, contraindicated with liver disease or CYP3A4 inhibitors
ramelteon - melatonin receptor antagonist (suprachiasmatic nucleus)
- no dependence
all insomnia drugs - adverse effects include headache, dizziness
52
triptans
5-HT1b/d AGONIST --> induce vasoconstriction
- inhibit trigeminal nerve firing
- prevent VIP release
adverse effects - coronary vasospasm (so dont give to CAD pts), mild paresthesia, serotonin syndrome
53
inhaled anesthetics
drugs with decreased blood solubility = rapid induction and recovery (induction based on how quickly you can equilibrate alveolar concentration with blood stream concentration, anesthetic acts when it is in the gas phase in blood)
- higher solubility in blood means that more anesthetic must be absorbed before it can be transferred to other tissues
- higher peripheral tissue solubility means more anesthetic is extracted from arterial blood --> AV gradient is greater --> blood saturation takes longer, so brain saturation takes longer
increased solubility in lipids = potent
-anes, N2O
N2O - fast induction, low potency
halothane is opp
myocardial depression, respiratory depression, N&V, increased cerebral blood flow (decreased cerebral metabolic demand)
hepatotox (halothane), nephrotox (methoxyflurane), enflurane (epileptogenic), expansion of trapped gas in body (N2O)
halothane hepatitis - metabolized by CYP450 --> metabolites lead to hepatocyte damage
- centrilobular hepatic necrosis - indistinguishable from viral hepatitis
malignant hyperthermia (AD) - also induced by sux
- mutations in VS_RyR -- > increased Ca2+ from SR
- Ca-ATPase overworks to get Ca back into SR --> ATP depletion, heat generation --> rhabdomyolysis --> release of K, myoglobin, and creatine kinase into circulation
- dantrolene - RyR antagonist, also used in neuroleptic malignant syndrome
54
opioids
...loperamide, dextromethorphan, diphenoxylate, pentazocine
mu (endorphins), k (dynorphin), d (enkephalin)
open K+ channels, close Ca2+ --> decrease synaptic transmission --> inhibit release of Ach, NE, 5HT, glutamate, substance P
OD: miosis, bradycardia, hypotension (due to histamine release)
uses - ..., acute pulmonary edema
adverse effects - N&V, miosis (except meperidine)
others:
- pentazocine - agonist/weak antagonist, used for analgesia, can cause withdrawal symptoms if pt is on opioid antagonist
- butorphanol - agonist/partial agonist, used in severe pain (labor, migraine), causes less respiratory depression but OD is not easily reverse with naloxone, can cause withdrawal symptoms if pt is on opioid antagonist
- tramadol - weak agonist, inhibits 5HT and NE reuptake
- involved with many NTs
- chronic pain, decreases seizure threshold, serotonin syndrome
55
NM blockers
used in surgery, mechanical ventilation
depolarizing = sux - AchR AGONIST --> sustained depolarization --> prevents muscle contraction
phase 1) prolonged depolarziation, no antidote
2) repolarized but blocked - AchR available but desensitized, can be reversed with AchE inhibitors
- complications: hypercalcemia, hyperkalemia, mal hyperthermia
nondepolarizing - cur, competitive antagonists
- can cause prolonged paralysis
- reverse with: neostigmine + atropine, edrophonium, AchE inhibitors
56
muscle relaxants
Baclofen - activates GABA_B at SC --> skeletal muscle relaxation
- used in MS, to relive muscle spasms
cyclobenzaprine - central acting skeletal muscle relaxant
- related to TCAs - similar anticholinergic effects
57
Alzheimers
presentation - elderly with memory impairment and higher cortical dysfunction (aphasia, agnosia, apraxia)
- apraxia - inability to excute learned purposeful movements
senile plaques and NF tangles
- can have associated b-amyloid angiopathy
- amyloid in Alzheimers is red and turns yellow-green under birefringence
(vs amyloid deposition systemically - b-sheet, apple-green)
drugs:
memantine - NMDA_R antagonist, helps prevent excitotox (mediated by Ca2+)
donepezil, galantamine, rivastigmine, tacrine - AchE inhibitors
adverse effects - dizziness, confusion
58
IV anesthesia
The Mighty King Proposes to Oprah
Thiopental (barb) - high potency, used for induction, rapidly redistributes into fat and tissue, DEcreases cerebral blood flow
Midazolam- endoscopy
Ketamine (arylcyclohexamines) - PCP analog, block NMDA receptors, increase cerebral blood flow, increases pulse and BP
Propofol - potentiates GABA_A, can cause hypotension (systemic vasodilation)
Opioids (morphine, fentanyl) - general anesthesia
59
local anesthetics
esters and amIdes
in infected (acidic) tissue - alkaline anesthetics are charged (think NH2+) --> cant penetrate membrane --> need more anesthetic
order of nerve blockade - small-diameter fibers > large diameter, myelinated > unmyelinated, and size factor predominates
- loss: 1 pain, 2 temp, 3, touch, 4 pressure
ADRs: CNS excitation, bupivicaine (cardiotox), arrhythmias (cocaine), metHb (benzocaine)
60
cavernous (ca-venous) sinus
cav sinus - pituitary - cav sinus
collects blood from eye + superficial cortex --> cavernous sinus --> IJ
```
optic chiasm (CN2) - then nerves descend in order, also have postG sympathetic pupillary fibers
CN6 runs with internal carotid
```
cavernous sinus syndrome - variable ophthalmoplegia, decreased corneal sensation, Horner syndrome, occasionally decreased maxillary sensation
- CN6 is most susceptible to injury
- CN6 palsy - eye is medially deviated
cavernous hemangioma = above tentorium cerebelli
- located in brain parenchyma
- clusters of dilated, thin-walled capillaries with little-no intervening nervous tissue
- seizures
61
vertigo
peripheral - inner ear (semicircular canal debris, vestibular nerve infection, Meniere disease, BPPV) --> delayed horizontal nystagmus with positional testing
- Meniere - vertigo, ringing, hearing problems unilaterally
central vertigo - brain stem, cerebellar lesion
- directional or vertical nystagmus, skew deviation, diplopia, dysmetria
- immediate nystagmus with positional testing
- these pts will also be unable to perform tandem walking
62
movement disorders
athetosis, chorea - BG lesion
dystonia - sustained, involuntary muscle contractions
hemiballismus - half-of-body ballistic, contralateral subthalamic nucleus (lacunar stroke)
intention tremor - cerebellar dysfunction
myoclonus - jerks, hiccups, metabolic abnormalities
63
idiopathic intracranial HTN (pseudotumor)
factors - female, obese, vitamin A tox, tetracycline, danazol
headache, diplopia (CN6 palsy)
treat with weight loss, acetazolamide, topiramate, invasive procedures (shunt, optic nerve sheath fenestration)
64
headaches
cluster - *periorbital features*
- acutely used sumatriptan, 100% O2
- prophylaxis - verapamil
tension - amitriptyline for chronic pain
migraine - 4-72hrs, due to irritation of CN5, meninges, or blood vessels
- acute - NSAIDS, triptans, ergots
- prophylaxis - lifestyle changes, b-blockers, CCB, amitriptyline, topiramate, valproate
v. s. trigeminal neuralgia - repetitive, unilateral, shooting pain down CN5 distribution, < 1 min
- treat with carbamazepine (same mechanism as phenytoin) = decreases Na current (by reducing the ability of Na channels to recover from inactivation)
- side effects - bone marrow suprression, SIADH, and P450 inducer
65
brain lesions
frontal lobe - reemergence of primitive reflexes
amygdala - Kluver-Bucy syndrome - disinhibited behavior (hyperphagia, hypersexuality, hyperorality)
- HSV1 encephalitis
frontal eye field --> contralateral PPRF --> ipsilateral abducens nucleus....
frontal eye fields - eyes look towards lesion
paramedian pontine reticular formation - eyes look away from lesion
MLF in dorsal pons - ...nystagmus of contralateral eye with abduction
dominant PARIETAL cortex - agraphia, acalculia, finger agnosia, LR disorientation
cerebellum
- hemisphere - affects ipsilateral limbs, fall to side of lesion
- vermis - central body ataxia, dysarthria, degeneration in chronic alcoholics
reticular activating system (midbrain) - coma
superior colliculus - stroke, hydrocephalus, pinealoma
- Parinaud syndrome - paralysis of conjugate vertical gaze, absent pupillary light reflex, impaired convergence
66
primitive reflexes
disappear w/i first year of life - as frontal lobe matures and myelination of the CST is completed
Moro - hang on for life
Rooting - nipple seeking
Suckling
Palmar - baby holds finger
Plantar reflex - toes dorsiflex/spread (Babinski in adult)
Galant - stroking along spine causes flexion towards stimulated side
67
clinical reflexes
Achilles - S1,2 buckle my shoe
Patellar - L3,4 kick the door
Biceps, brachioradialis - C5,6 pick up sticks
Triceps - C7, 8 lay them straight
Cremasteric - L1,2 make the testes move
Anal wink - S3,4 winks galore
conus medullaris syndrome = lesions at L2 - flaccid paralysis of bladder, rectum, impotence, saddle anesthesia
cauda equina syndrome
- damage to S2-S4 - provide the sensory and motor innervation of LEs, pelvic floor, and sphincters
- loss of anal wink reflex, loss of ankle-jerk reflex
- low back pain, saddle anesthesia
- S3-S5 damage --> bowel/bladder dysfunction
68
vertebral disc herniation
C1-7 exit ABOVE vertebra, all else below
nerve below herniated disc is affected - nucleus pulposus herniates through outer ring
69
cranial nerve reflexes
afferent - reflex - efferent
V1 (opthalmic branch) - corneal - 7 (temporal branch), processing in pons
- can be impaired by damage to superior orbital fissure (CN3-6)
V1 - lacrimation - V7
2 - pupillary - 3
9 - gag - 10
jaw jerk - V3
- 3 muscles close the jaw - Masseter, teMporalis, Medial pterygoid (Ms munch)
- 1 opens - lateral pterygoid (Lateral lowers)
70
NTs and locations
Ach - Basal nucleus of meynert
- secrete decreased amts of Ach in Alzheimers
GABA - NAccumbens
NE - Locus ceruleus, increased in anxiety
- dorsal pons
Serotonin - raphe nucleus (located in brainstem)
- play a role in sleep-wake cycle, anxiety/mood, sexuality, eating, impulsivity
red nucleus - located in anterior midbrain
- neurons participate in motor coordination of UE
71
sleep phys
circadian rhythm - suprachiasmatic nucleus (hypothal)
SCN --> NE --> pineal gland --> melatonin
alcohol, benzos, barbs associated with decreased REM sleep and delta wave sleep
- NE associated with decreased REM sleep
- benzos good for night terrors and sleepwalking (decrease REM and N3 stage)
oral desmopressin used for bedwetting
awake eyes open (better have your eyes open when you're awake) - beta waves (high freq, low amplitude)
awake eyes closed - alpha
non-REM
- N1 (5%) - theta, light sleep
- N2 (45%) - sleep spindles + K complexes, deeper sleep, teeth grinding can occur
- N3 (25%) - delta (lowest freq, highest amplitude), deepest non-REM, sleepwalking, night terrors, bedwetting (N3 is scary)
REM (25%), occurs every 90 min with progressively increasing duration - beta
- loss of motor tone, brain uses inc O2, variable pulse and BP, increased Ach
- dreams
- sexual arousal
- memory processing fx
- depression decrease REM latency, increases total REM
- extraocular movements due to PPRF
= BATS Drink Blood
elderly - decreased REM and slow-wave sleep, increased sleep onset latency, increased early awakenings
72
aphasia
Repetition IMPAIRED:
Broca - expressive, frontal lobe
- Brocas aphasia - may say a few small words
- cant repeat
Wernicke - comprehension, temporal lobe
- may make up new words, speak in sentences that have no meaning
- repetition is poor
Conduction - fluent, comprehension is intact, damage to arcuate fasciculus
- pt unable to repeat words
Global
Repetition INTACT
- transcortical motor - like Brocas, but can repeat words (brocas area spared)
- transcortical sensory - like Wernickes but can repeat words
- transcortical mixed - nonfluent, impaired
73
seizures
partial: originate in medial temporal lobe, often preceded by aura
simple - no LOC, complex - impaired consciousness
generalized
absence - 3Hz spike
myoclonic, tonic-clonic, tonic, atonic (drop seizures, mistaken for fainting)
74
cranial nerves
10/12 nerves arise in brainstem
```
1-2-3-4 above the pons
- 4 arises dorsal (side that is stuck to the cerebellum) and immediately decussates
in the pons: 5(lateral)....6-7-8
in medulla: 9-10-11
between pyramid and olive: 12
```
75
dorsal features of brain stem
side that is stuck to the cerebellum
pineal gland
superior colliculi - conjugate vertical gaze center
inferior colliculi - auditory center
76
substantia nigra
midbrain
77
spinal tracts
DCML:
somatosensory receptor --> first order neuron, cell body in DRG --> ascend ipsilaterally in dorsal column --> synapse 1 in nucleus gracilis and nucleus cuneatus in ipsilateral medulla -->
spinothalamic/anterolateral:
78
PKU v.s tyrosinemia
PKU - *intellectual disability, growth retardation, *seizures, hypopigmentation and eczema (excess phe inhibits tyrosinase), musty body odor
tyrosinemia - due to deficient fumarylacetoacetate hydrolase
- signs and symptoms due to intermediates of tyrosine metabolism
- liver involvement, Fanconi syndrome, growth failure, rickets
- treat with nitisone --> otherwise can have neurologic crises (MSE changes, peripheral neuropathy) and death
79
dopamine hydroxylase deficiency
dopamine --> NE
deficiency - dysautonomia
- ptosis, orthostatic hypotension, hypoglycemia, and hypothermia
80
HIV-associated dementia
pts with CD4 <200
SUBcortical dementia - attention/working memory (recall) problems, executive dysfunction, slow information processing
- HIV affects subcortical/deep gray matter structures
inflammatory activation of microglial cells
1) HIV-infected monocytes enter brain
2) activated macrophages and microglia form microglial nodules around area of necrosis
2) neuronal damage from cytokines and direct toxic effects of HIV-derived proteins
81
viruses in the brain
HSV - intranuclear acidophilic inclusions
CMV - intranuclear basophilic inclusions
82
sciatic nerve
( L4-S3) sciatic nerve --> tibial nerve and common peroneal (swings anterior)
- sciatic nerve innervates hamstrings (posterior thigh muscles)
- damage to tibial nerve will affect plantar flexion and sensation of plantar foot
- injury to popliteal fossa = weakness on foot plantar flexion (tibial nerve innervates gastroc, soleus, plantaris), can also see weakness on inversion and toe flexion
- tibial nerve injury at tarsal tunnel - sensory loss over sole BUT plantflexion and inversion remain intact (these branches are earlier)
- pos straight leg raise test - sciatic nerve root irritation
common peroneal --> deep peroneal (medial) and superficial peroneal (lateral)
- common peroneal nerve contacts lateral neck of fibula, susceptible to compression injury
- damage to deep peroneal = foot drop - cant dorsiflex or extend toes
- superficial peroneal --> eversion and sensation over dorsolateral foot
83
femoral nerve
from L2,3,4
- knee extension - quads
- hip flexion - iliopsoas
- forms saphenous nerve (anterior lower leg) - sensation for arch of foot, medial foot, shin, and anteromedial thigh
femoral block at inguinal crease - anesthetizes skin and muscles of anterior thigh, femur, and knee
- also anesthetizes saphenous nerve
- femoral block for torn quad
femoral canal only contains lymphatics
84
Cryptococcus
yeast form only
pigeon droppings and soil - enters through respiratory tract
predilection for CNS - CSF doesnt contain alternative complement pathway
85
pudendal nerve
S2-4
ischial spine is the landmark for the pudenal nerve block - used in vaginal and perineum surgeries
86
obturator nerve
innervates thigh adductor muscles and medial skin of thigh
87
anti-epileptics
lamotrigine - blocks VS-Na channels
- pts can develop benign rash or a life-threatening rash (SJS-TEN)
- SJS involves < 10% of body, TEN involves >30% of body
- characterized by flu-like symptoms, mucocutaneous lesions, epidermal necrosis
- rash means you HAVE to discontinue lamotrigine
others with SJS/TEN - carbamazepine, phenobarbital, phenytoin
88
phrenic nerve
C3-C5 = phrenic nerve
irritation can occur with lung tumors --> dyspnea, hiccups, referred pain to shoulder
other effects of lung tumors
- pancoast tumor can cause Horner syndrome, brachial plexus (C5-T1) and shoulder pain, upper extremity edema, and SC compression/paraplegia if tumor extends into intervertebral foramina
- centrally located tumor - SVC syndrome
89
Rabies
ssRNA, bullet-shaped capule
- glycoprotein spikes that bind to NAchR
- retrograde travel to CNS
starts with flu-like prodome
progresses to fever, agitation, disorientation, pharyngospasm, photophobia --> flaccid paralysis coma and death
pharyngospasm --> avoidance of food and water
- dysphagia + hypersalivation = foaming
90
CJD
rapidly progressive demnentia and myoclonic jerks of extremities
91
pseudodementia
cognitive impairment associated with depression
92
diabetic neuropathy
decrease in vibratory sensation, proprioception, and temperature sensation
diminished reflexes, motor weakness
93
Guillan-Barre
Campy then GB
antibodies against pathogen cross-react with ganglioside components of myelin
- segmental demyelination and endoneural inflammatory infiltrate
ascending paralysis
- hits respiratory muscles
- Bell's palsy - CN7
- areflexia
94
Beriberi
can cause demyelination of peripheral nerves - NO inflammation
- classically distal LE is involved
95
subthalamic nucleus
below thalamus, above substantia nigra, medial to internal capsule
damage to subthalamic nucleus - decreases the excitation of the globus pallidus internus --> reduces inhibition of thalamus
- thalamus is MORE excited --> contralateral hemiballism
- damage is most commonly due to a lacunar stroke
96
internal capsule
damage will have contralateral pure motor or combined sensorimotor deficits
97
Wilson's disease
atrophy of lentiform nucleus (globus pallidus and putamen)
98
VPLN or VPMN
nuclei in thalamus
damage results in complete contralateral sensory loss
damage to thalamus - thalamic syndrome, contralateral burning or stabbing
99
pts with longstanding HTN
AV nicking on fundoscopic exam
100
synaptophysin
neurons, neuroectoderm, neuroendocrine cells
101
GFAP
glial cell tumors
| = astrocytomas, oligodendrogliomas, ependymomas
102
mammillary body
Papez circuit of limbic system - involved in cortical control of emotion and memory
fornix --> projects to mammillary bodies
103
corpus callosum
splenium or damage of tail - alexia without agraphi
104
NAch receptors
upon binding 2 molecules of Ach --> Na and Ca influx and K outflux --> end-plate potential is generated
105
febrile seizures
supportive care, antipyretics - though antipyretics will no reduce the risk of further febrile seizures (due to the presence of circulating inflammatory mediates that lower the seizure threshold)
v. s. heat stroke in kids
- oxidative P stops at 108F --> end organ damage
106
neurosyphilis
tabes dorsalis - sensory ataxia and Argyll Robertson pupils (small irregularly shaped pupils that dont respond to light)
- areflexia, neurogenic bladder (overflow incontinence)
progressive dementia and generalized paralysis
107
NMDA receptor blockers
ketamine, felbamate, memantine
108
ear
stapedius nerve stapedius oscillates more widely --> hyperacusis
- ipsilateral hyperacusis is seen in Bell's palsy
tensor tympani - innervated by mandibular branch of V3
109
orbital floor fracture
infraorbital nerve
110
facial nerve
motor of the face
impaired by temporal bone or zygomatic orbit fractures
111
hypothalamic nuclei
ventromedial - satiety --> destruction leads to hyperphagia
lateral - hunger
anterior - heat dissipation
posterior - heat conservation
arcuate - secretes dopamine, GnRH, and GHRH
paraventricular - ADH, CRH, oxytocin, TRH
supraoptic - ADH, oxytocin
suprachiasmatic - circadian, pineal gland function
in kids - hypothalamic lesions are most likely gliomas
- adults - mets
112
antiseizure drugs
phenytoin, carbamazepine - blocks Na+ channels
valproate - blocks Na+ channels and increases GABA levels
levetiracetam - modulates GABA and glutamate release
ethosux - blocks thalamic T-type Ca2+ channels
vigabatrin - irreversible inhibitor of GABA transaminase, so GABA is not degraded
- can be used in treatment-resistant epilepsy
status epilepticus - lorazepam _ phenytoin (long-acting anti-convulsant)
113
brain injury and edema
ischemic injury:
- cytotoxic edema - due to impaired Na/K ATPase
- vasogenic edema - increased vasc permeability due to pro-inflammatory cytokines
side note - neutrophils do infiltrate the brain during the first 48 hrs
114
sensory receptors
phasic receptors - Pacinian corpuscles (subQ and IM), Meissner corpuscle (fingertis), hair follicles
tonic receptors - Merkels, Ruffini, tactile disks (hairy skin)
- rate of APs encodes stimulus intensity
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