Neurology Flashcards
How does cisatracurium work?
Competes with acetylcholine binding at postsynaptic nicotinic receptors on motor end plate; acetylcholinesterase inhibitors such as neostigmine reverse neuromuscular blockade
Degraded in plasma by ester hydrolysis and Hofmann elimination (pH and temperature dependent - acidotic and hypothermic patients have longer half life)
Laudanosine is a metabolite of cisatracurium, can accumulate with repeated dosing or during continuous infusion, can cause hypotension
List the normal EEG waves
Normal awake/asleep = alpha and beta (high frequency low amplitude); burst suppression = low frequency high amplitude
Symptoms of epidural hematoma
60% of adults have a lucid period, less common in kids
Headache, nuchal rigidity, ipsilateral pupillary dilation, contralateral hemiparesis, coma
List 3 types of dystrophinopathy
- Duchenne muscular dystrophy
- Becker muscular dystorphy
- X-linked dilated cardiomyopathy
How does Emery-Dreifuss muscular dystrophy present?
Early childhood, joint contractures (elbows, ankles, cervical spine), later skeletal muscle weakness
Mutationes in genes encoding emerin, lamin A, lamin C, nesprin (EMD, FHL1, LMNA)
What impact does hypothermia have on neuromuscular blockade?
Prolonged duration of action – doubles for each 2 degree drop below 36.5 C
What percent of kids with VP shunt malfunction have a negative CT scan?
13 to 30%
Treatment for acute dystonia resulting from haldol
Diphenhydramine or benztropine
Dystonia is an unpredictable adverse effect of antipsychotic meds characterized by abnormal and prolonged contraction of the muscles of eyes, head, neck, limbs, or trunk; excess nigrostriatal dopamine blockade leading to excess cholinergic output
What are the symptoms of infant botulism?
Generalized weakness, hypotonia, decreased activity, poor feeding, constipation, cranial nerve palsy, sluggish pupils, hypoventilation with shallow rapid breaths, occasional respiratory failure; no fever
Symmetric descending paralysis, fatiguability with repetitive stimulation of muscle contraction (e.g. repeatedly assess pupillary light reflex over 1-3 min)
Enema with sterile water for sample to detect toxin, treat with botulism immune globulin
What is Nusinersen?
Treatment for spinal muscular atrophy (SMA) type 1
Intrathecal, binds specific sequence in SMN2 gene, increases production of functional SMN protein
CSF in botulism vs. guillane barre?
Botulism: normal
GBS: high protein
Hemodynamic impact of sevoflurane?
Hypotension (low SVR), cerebral vasodilation, decreases cerebral metabolic rate, preserves cerebral autoregulation
Goal cerebral perfusion pressure by age?
Infant >40
Child >50
Adult >60
How do reversal agents work?
Neostigmine - acetylcholinesterase inhibitor, so makes ACh last, but if there’s still NMB around can have re-paralysis (“recurarization”), can cause bradycardia - procholinergic
Sugammadex - noncompetitive, reverses vec and roc only, encapsulates the aminosteroid through chelation
Sugammadex WON’T reverse succinylcholine or atracurium/cisatracurium (those degraded in plasma)
There is no reversal for succinylcholine
Ketamine
Dissociative state (sedation), amnesia, and analgesia without cardiac or respiratory depression
Bronchial smooth muscle dilation
N-methyl-D-aspartate receptor antagonism and u-opioid receptor agonism
Causes release of catecholamines, blocks reuptake of norepinephrine; also has direct myocardial depressant activity, use with caution in catecholamine-depleted patients
Contraindicated: hypertension, aneurysm, thyrotoxicosis, psychotic disorders
Haloperidol
Typical antispychotic agent
QTc prolonging, extrapyramidal effects, drowsiness, dystonia, tremor
Butyrophenone class, nonselective blockade of brain postsynaptic dopaminergic D2-receptors
Review the cellular pathways involved in neuronal injury following oxygen deprivation
Three phases of injury:
1. Exhaustion of cells energy stores
- Excitatory neurotransmitters, inflammation, ROS, necrosis (encephalopathy and seizure)
>Glutamate binds NMDA and AMPA receptors, persistent stimulation causes excitotoxicity - damage to neurons with glutamate receptors
>AMPA receptors assist with removal of Mg from NMDA channel allowing influx of Ca; persistent glutamate activation of some AMPA receptors allowing Ca and Zinc in cause injury, increased expression of these receptors on surviving neurons - Neuronal apoptosis long after initial injury
>Reperfusion injury causes delayed death via generation of ROS which cause further damage
>Zinc contributes to chronic neuronal injury after HIE - depletion in presynaptic and accumulation in postsynaptic neurons (both depletion and accumulation of zinc can cause apoptosis)
What are the three mechanisms of action of methadone?
Mu receptor
NMDA receptor antagonist
Blocks serotonin and norepinephrine reuptake
Review neuromuscular blockade depolarizing/nondepolarizing mechanisms of action
Depolarizing (succinylcholine): bind to and activate ACh receptors to cause initial dpolarization, not hydrolyzed by acetylcholinesterase so stays bound, prevents new action potential – flaccid paralysis after the fasciculation
Good: rapid onset (30-60 sec), short duration of <5min; RSI
Bad: bradycardia (muscarinic ACh receptor activation), can give with atropine or glycopyrrolate, can also get rhabdo, hyperK - risk of cardiac arrhythmia
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Nondepolarizing (roc, vec, cis): Competitively block ACh receptors, can be reversed by acetylcholinesterase inhibitors such as neostigmine (can cause bradycardia), also sugammadex - binds roc and vec
How does dexmedetomidine work?
Selective alpha-2 agonist
Sympatholytic effect - reduces norepinephrine release
Sedative effect - reduces activity in locus coeruleus in CNS where there are a large number oa alpha2 adrenoceptors
Mild analgesic properties - good adjunct
Hypo/hypertension; hyper tension most often in younger patients who get a bolus (reflexive bradycardia), caused by peripheral alpha2 stimulation with vasoconstriction
Equation for cerebral blood flow (CBF)
CBF = CPP/CVR
CPP = (MAP - ICP)
CBF of infant is > adult, peaks at age 4 years, then declines to adult levels
Effect of O2 and CO2 on cerebral blood flow
CO2: changes in brain periartriolar pH lead to NO synthase activity > cGMP, linear increase in CBF for increase in PaCO2 between 20-80 (4% per mmHg)
O2: flat curve except at PaO2<50 mmHg
What is Dravet syndrome
Severe Myoclonic Epilepsy of Infancy
Prolonged seizures, developmental delay, hypotonia, ataxia, speech impairment
SCN1A mutations, increased sodium into neurons
First line: clobazam, valproic acid
Second line: topiramate, stiripentol
Third line: clonazepam, keppra, zonisamide
Other: ketogenic diet, medical marijuana, fenfluramine (over age 2)
Avoid medications that bind to sodium channels: phenytoin, cabamazepine, oxcarbazepine, lamotrigine (worsen seizures by lowering GABA inhibitory tone)
Also avoid: phenobarbital, vigabatrin
Miller Fisher variant of GBS symptoms
ataxia, areflexia, ophthalmoplegia
Diagnostic findings in GBS (MRI, CSF)
MRI: normal to nerve root enhancement
CSF: high total protain otherwise normal (albuminocytologic dissociation)
ICP readings falsely elevated or decreased by transducer position change?
If head is below transducer, falsely low, decreased drainage
If head is above transducer, falsely high, too much drainage
Criteria for serotonin syndrome?
Spontaneous clonus
Inducible clonus with agitation or diaphoresis
Ocular clonus with agitation or diaphoresis
Tremor and hyperreflexia
Hypertonia and temperature over 38 °C and ocular or inducible clonus
can cause rhabdo
MELAS
Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes
-mitochondrial disorders usually affect the aerobic tissues - heart, muscles, and nervous system
- typically have stroke-like events
cerebral edema types
Oncotic edema is a process by which Starling forces drive water to enter contused neurons (which have increased osmolarity), causing edema in the affected brain. Vasogenic edema occurs as a result of the disruption of the tight junctions of the blood brain barrier. Cytotoxic edema is caused by adenosine triphosphate (ATP) depletion, which disrupts ion channels. This disruption allows water to enter and causes cellular swelling.
Glasgow Coma Scale intubated
Eye and motor only, max 10T, min 2T
Pharmacokinetic properties of etomidate?
Highly protein bound so in protein deficiency there will be more free etomidate available
Most significant adverse effect is adrenal suppression - dose dependent inhibition of 11-beta-hydroxylase lasting 6-12 hrs (makes cortisol); contraindicated in sepsis for that reason
Binds to GABA sites, increases affinity for GABA
Minimal hemodynamic and ICP effects
Symptoms of spinal muscle atrophy
Degeneration of anterior horn cells
Regression of motor milestones, tongue fasciculations, areflexia, hypotonia, extremity weakness (proximal)
SMN1 mutation, meaning patient has to rely on reduced production by SMN2
Nusinersen alters the pre-messenger RNA splicing, promoting increased production of full-length SMN
Onasemnogene is adenovirus-associated vector that replaces nonfunctioning SMN1 gene
Type 0 (worst/earliest) to Type 4 (Adult onset)
Train of four with non-depolarizing vs. depolarizing neuromuscular blockade?
Non-depolarizing shows fade, number of twitches correlates to percent of receptors blocked (1 twitch 90%, 2 twitches 85%, 3 twitches 80%, 4 twitches 75% or less)
> You want a train of four ratio (fourth to first twitch amplitude) >0.9 before extubation
Depolarizing shows equal but lower amplitude
Risk of lots of lorazepam IV?
Propylene glycol, osmolar gap anion gap acidosis
Likely ingestion with toxidrome of somnolence, hypotension, bradycardia, hypothermia, normal-sized pupils (+/- miosis), normal urination
clonidine
Typical age of presentation of AVM
Often around puberty, may be influenced by hormonal changes, maybe genetics
Not associated: stimulant use, tobacco use, physical activity
Neuroleptic malignant syndrome vs. Malignant hyperthermia
NMS: fever, AMS, rigidity with HYPOreflexia; extrapyramidal symptoms - tremor, chorea; CK high, leukocytosis
Occurs through blockade of dopamine receptor - typical and atypical antispychotics or rapid withdrawal of agonists (levodopa)
Rx: supportive, dantrolene, bromocriptine
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Serotonin syndrome has clonus, HYPERreflexia
Malignant hyperthermia occurs in immediate peri-anesthetic period (hypercarbia, muscule rigidity, fever, tachycardia)
