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0114 - Neuro 3/3 Flashcards

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1
Q

Genetics affecting course of Alzheimers?

A

Early onset associated with APP (21), presenilin-1 (14), and preseinili-2 (1). Late onset with ApoE4 (19). ApoE2 (19) appears to be protective

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2
Q

Senile plaques vs. neurofibrillary tangles

A

Senile plaques are extracellular Beta-amyloid core. amyloid-Beta comes from cleavage of amyloid precursor protein (APP). Neurofibrillary tangles are INTRAcellular, hyperphosphorylated TAU protein = insoluble. Tangles correlate to degree of dementia.

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3
Q

Frontotemporal dementia vs. Lewy body dementia

A

Personality and parkinsonian vs. Visual hallucination -> parkinsonian. Pick bodies (spherical tau protein aggregates) + fonrtotemporal atrophy vs. alpha-synuclein defect.

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4
Q

Acute inflammatory demyelinating polyradiculopathy

A

Most common Guillan-Barre variant. Autoimmune condition associated w/ infection (Campy and CMV) -> destruction of Schwann cells leading to a simmering ascending muscle weakness/paralysis starting from lower extremities. Autonomic findings! Tx - respiratory support, plasmapheresis, IVIG. LP shows increased protein with NORMAL cell count and increased protein.

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5
Q

PML

A

Progressive multifocal leukoencephalopathy. Destruction of OLIGO’s associated with JC. Found in AID’s and inc. risk with natalizumab (MS drug). Usu. fatal.

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6
Q

ADEM

A

Acute disseminated encephalomyelitis. After infection (measles, VZV) or vaccination (rabies, smallpox), multifocal perivenular inflammation and demyelination

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7
Q

Metachromatic leukodystrophy

A

AR, arylsulfatase A deficiency -> buildup of sulfatides -> impaired myelin sheet production -> central and peripheral demyelintation with ATAXIA and dementia. Many-colored Arya becomes ataxic in the sulfur pits.

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8
Q

Charcot-Marie-Tooth

A

Progressive hereditary nerve disorder 2/2 defective protein production for structure or function of peripheral nerves or myelin. Typically AD, scoliosis, high or flat arches

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9
Q

Krabbe disease

A

Galactocerebrosidase (Gaucher is glucocerebrosidase) -> buildup of galactocerebroside and pyschosine -> myelin destruction -> peripheral neuropathy, dvpt delay, optic atrophy, globoid cells. Krabs are delayed.

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10
Q

Adrenoleukodystrophy

A

X-linked! Metabolism of VLCFA’s -> buildup in nervous, adrenals (crisis), testes. ADRENO! luekodystrophy.

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11
Q

Status epilepticus

A

Continuous seizure for > 30 minutes or recurrent sz without regaining consciousness between sz. Emergency

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12
Q

Myoclonic vs. tonic-clonic vs. tonic vs. atonic sz.

A

Myoclonic are quick, repetitive jerks while tonic-clonic are grand mal alternating stiffening and movement. Tonic sz = stiffening. Atonic sz = “drop” sz.

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13
Q

Etios of sz for children?

A

Genetic, infection (febrile), trauma, congenital, metabolic

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14
Q

Cluster vs. Tension vs. Migraine HA’s regarding DURATION

A

Cluster - 15min-3 hrs repetitive. Tension HA > 30 min and constant. Migraines are 4-72 hours.

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15
Q

Cluster HA vs. trigeminal neuraglia

A

TN produces repetitive shooting pain in distribution of CN V typically lasting < 1 min. Cluster HA pain is > 15 min.

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16
Q

Tx for cluster headaches?

A

Inhaled oxygen and sumatriptan vs. analgesics or amitriptyline for chronic pain

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17
Q

Peripheral vs. central vertigo

A

Peripheral is more common (inner ear etio). Positional testing leads to a delayed horizontal nystagmus. Central is brain stem or cerebellar with directional change of nystagmus, dipolopia, dymetria, immediate nystagmus with positional testing

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18
Q

Sturge-Weber

A

Sporadic, port-wine Stain, Tram track, Unilateral, Retardation, Glaucoma, GNAQ, Epilepsy. (SSTURGGE). Activating mut -> dvpt anomaly of neural crest derivatives. Port-winte in V1/V2 distribution. Ispsi leptomeningeal angioma -> sz/epilepsy. Congenital NON-inherited. GNAQ sporadic.

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19
Q

Tuberous sclerosis

A

HAMARTOMAS = Hamartomas in CNS/skin, Angiofibromas, MR, Ash-leaf spots, cardiac Rhabdomyoma, TS, autosomal dOminant, Mental retardation, renal Angiomyolipomas, Sz, Shagreen patches. Increased subependymal astrocytomas.

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20
Q

NF-1

A

Cafe-au-lait, Lisch nodules, NF’s in skin, optic gliomas, pheochromocytomas. NF1 is a tumor suppressor gene (Ras regulator) on chromosome 17.

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21
Q

VHL

A

Cavernous hemangiomas in skin, mucosa, organs, b/l RCC, hemangioblastoma in retina, brainstem, cerebeullum, and pheochromocytomas. AD. VHL is tumor suppressor on chromsome 3 -> constitutive HIF (transcription factor) expression -> angiogenic growth factors

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22
Q

Gliobastoma multiforme

A

Hemispheres, “Butterfly glioma,” Astrocytes stain’d for GFAP, pseudopalisading pleomorphic tumor cells with central areas of necrosis

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23
Q

Meningioma

A

Arachnoid cells, EXTRA-exial. Dural-tail. Often asymptomatic with sz or focal neuro. Path w/ spindle cells concentrically and Psammoma bodies

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24
Q

Hemangioblastoma

A

VHL associated when w/ retinal angiomas. Cerebellar. Often produce EPO => secondary polycythemia. Path - closely arranged, thin-walled caps with minimal parenchyma

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25
Schwannomas
Cerebellopontine angle. Schwann cell. S100 POS. B/l acoustic schwannomas found in NF-2.
26
Oligodendoglioma
Rarer, slower growing. Frontal lobe. Path - fried egg cells (oligo's) and chicken-wire capillary pattern. Often calcified.
27
Pilocytic astrocytoma
In children, often found in posterior fossa. Well-circumscribed. Benign w/ good prognosis. Path - GFAP POS, Rosenthal fibers (corkscrew, eosinophilic), cystic on gross.
28
Medulloblastoma
PNET. Highly malignant cerebellar. Compress 4th ventricle; Drop metastases into spinal cord. Path - Homer-Wright rosettes. Solid, small blue cells.
29
Ependymoma
Usu. FOURTH ventricle. Hydrocephalus. Poor prognosis. Path - perivascular rosettes. Rod-shaped blepharoplasts (basal ciliary bodies) near nucleus.
30
Craniopharyngioma
Most common childhood supratentorial tumor derived from Rathke's pouch. Often calcified.
31
Uncal herniation
Ipsilateral CN III (blown and down and out), ipso PCA (contralateral homonymous hemianopsia), contralateral crus cerebra (ipsi paralysis)
32
Adrenergic glaucoma drugs
Epinephrine decreases aqueous humor synthesis via vasoconstriction (se of mydriasis so don't use in closed-angle). Brimonidine (alpha-2, decreases synthesis) w/ se of blurry vision, hyperemia, foreign body sensation, allergy, ocular. The beta-blockers are timlol, betaxolol, and carteolol.
33
Cholinomimetics used for glaucoma
Direct (pilocarpine, carbachol) and indirect (physostigmine, echotiophate). Contract ciliary muscle and open trabecular meshwork to increase outflow. SE include miosis and cyclospasm.
34
Prostaglandin used for glaucoma
Latanoprost (PDG2alpha) increases aqueous humor outflow and browns the iris.
35
Mechanism of opioid analgesics
Opioid receptors (mu = morphine, delta = enkephalin, kappa = dynorphin) to open K+ channels, close Ca2+ channels -> DECREASED synaptic transmission. Inhibit release of ACh, NE, 5-HT, glutamate, and substance P.
36
Butorphanol
PARTIAL mu-opioid receptor agonist and kappa-opioid receptor agonist. Used for severe pain (migraine and labor) with LESS reparatory depression. H/e, withdrawal symptoms if patient on full opioid agonist. Overdose hard to reverse with naloxone.
37
Tramadol
VERY weak opioid agonist that also inhibits 5-HT and NE reuptake. Chronic pain. Similar tox profile as opioids, decreases sz threshold, serotonin syndrome.
38
Ethosuximide
Absence sz. Blocks t-type Ca2+ channels. SE's fatigue, GI, HA, Itching, Stevens-Johnson
39
1st line acute tx for status vs. 1st line ppx for status?
Benzos (diazepam, lorazepam) vs. Phenytoin
40
Phenytoin
1st line tonic-clonic and ppx for status. Na+ channel inactivation. 0-order kinetics. Induces P450. Lots of SE (nystagmus, dipolpia, gingival hyperplasia, teraogeneis w/ fetal hydantoin syndrome, ale-like). Fosphenytoin is IV.
41
Carbamazepine
1st line for simple, complex, tonic-clonic sz, and trigeminal neuralgia. Na+ channel inactivation. SE diplopia, ataxia, blood dyscrasia, liver, teratogenesis, induces P-450, SIADH, Stevens
42
Valproic acid
1st line for tonic clonic. Used for partial sz and absence. Na+ channel inactivation and inhibition of GABA transaminase to increase GABA. GI, hepatotoxicity (rare but fatal, Neural tube defects, tremor, wt gain. Myoclonic sz and bipolar.
43
Gabapentin
Partial and tonic-clonic, peripheral neuropathy, postherpetic neuralgia, migraine ppx, bipolar. Inhibits high-voltage activated Ca2+ channels. SE - sedation and ataxia
44
Phenobarbital
Partial, tonic-clonic. Increases GABA action. 1st-line for neonates! sedation, tolerance, induce P-450, CV dep.
45
Topiramate
Partial and tonic-clonic. Blocks Na+ channels and increases GABA. Migraine prevention. Sedation, mental dulling, kidney stones, wt loss.
46
Lamotrigine
Partial, tonic-clonic, absence. Blocks voltage-gated Na+. Stevens-Johnson syndrome.
47
Levetiracetam (Keppra)
Partial, tonic-clonic. Unknown mech. No SE's noted.
48
Barbiturates - Mech and Tox
Increase DURATION of Cl- channel opening (GABA), decrease neuron firing. Contra'd in porphyria. Used for anxiety, sz, insomnia, induction of anesthesia (thiopental). Tox - CV depression, dependence, induces P450. Overdose tx is supportive. "Barbies are durable."
49
Benzos - Mech and Tox
Increase FREQUENCY of Cl- channel opening. Decreases REM sleep. Tox - dependence, CNS depression with alcohol, but less resp depression than barbiturates. Tx overdose w/ flumazenil. "Ppl that buy Benz's (and do benzos) are flippant."
50
Nonbenzo hypnotics - mech and tox
Zolpidem, Zaleplon, Eszopiclone. Act on BZ1 subtype of GABA receptor. Tox - ataxia,HA, confusion. Short duration b/c rapidly metabolized by LIVER. dec. dependence
51
What properties of anesthetics do we care about?
Solubility in lipids and blood. MAC - minimal alveolar concentration req. to prevent 50% from moving in response to noxious stimuli. Inc. solubility in lipids = greater potency (lower MAC). Inc. solubility to blood = slower cross to CNS = slower induction and recovery
52
Toxicities of inhaled anesthetics
Heptotoxicity (halothane), nephrotoxicity (methoxyflurance), proconvulsant (enflurane), expansion of trapped gas in body cavity (NO). All of these except NO and the addition of succinylcholine can cause malignant hyperthermia which is life-threatening HEREDITARY condition with fever and severe muscle contractions. Tx = dantrolene
53
IV anesthetics
Barbiturates, Benzos, Ketamine, Opioids, Propofol
54
Propofol
Sedation in ICU, rapid anethesia induction, short procedures. Less postop nausea than thiopental. Potentiates GABA.
55
Thiopental
IV barbiturate of high potency and rapid entry into brain. Induction and short surgical procedures. Rapid redistribution into tissue and fat (recovery quick). Decreased cerebral blood flow
56
IV midazolam
Commonly used for endoscopy. Used w/ gaseous anesthetics and narcotics. May cause severe post-op respiratory depression, decreased pressure, and anterograde amnesia
57
Ketamine
PCP analog that blocks NMDA (dissociative anesthetic). CV stimulant. Disorientation, hallucination, bad dreams. Inc. cerebral blood flow.
58
Local anesthetics
Amides are lidocaine, mepivacaine, bupivacaine. Esters are procain, cocaine, tetracaine.
59
Mech of local anesthetics
Block Na+ channels (inner portion) and preferentially bind to activated ones. Tertiary amines penetrate membrane uncharged, then after charge, bind ions.
60
Factors affecting the effectiveness of local anesthetics?
It's hard for charged, alkaline anesthetics to get into infected (acidic) tissue. Order of nerve blockade small diameter > large diameter. Then myelinated > unmyelinated. Lose pain, temp, touch, then pressure. Can give with vasoconstrictors like epi to enhance local action via dec bleeding and dec. systemic conc.
61
Local anesthetic toxicity
CNS excitation, CV tox (bupivacaine), HTN, hypotension, arrhythmias (cocaine)
62
Basic overview of paralytics
Used for surgery or mech ventilation. Selective for motor nicotinic receptors. Depolarizing vs. nondepolarizing = agonist vs. competetive antagonist
63
Succinylcholine
Strong ACh receptor agonist -> sustained depolarization and prevents muscle ctx. Complications - hyperCa, hyperK, malignant hyperthermia. Reversal in two phases. Phase 1 is prolonged depol. w/ no antidote. Phase 2 is repolarized but AChR desensitized and req. cholinesterase inhibitors
64
Dantrolene
Ryanodine receptor. Prevents release of Ca2+ from SR in skeletal muscle. Used for malignant hyperthermia and NMS.
65
Parkinsons drugs
BALSA = Bromocriptine, Amantadine, Levodopa, Selegiline, Antimuscarinics.
66
Selegeline
MAO-B inhibitor that prevents DA breakdown (MAO-B prefers to breakdown DA > NE and 5-HT). Other DA breakdown inhibitors are COMT inhibitors (entacapone and tolcapone)
67
Benztropine
Curbs excess cholinergic activity in Parkinsons as an antimuscarinic.
68
Memantine
Alzheimer's drug. NMDA receptor antagonist. Tox includes dizziness, confusion, hallucinations
69
AChE inhibitors for Alzheimer's
Donepezil, galantamine, rivastigmine.
70
HD drugs
Haloperidol (DA receptor antagonist). Inhibitors of vesicular monoamine transporter (VMAT) - tetrabenazine and reserpine.
71
Sumatriptan
5-Ht1b/1d agonist. Inhibits treigeminal n. activation and prevents vasoactive peptide release. t1/2 <2hrs. Used for acute migraines and cluster headaches. Tox = coronary vasospasm CONTRA = CAD or Prinzmetal angina

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