Neuro exam 1 Flashcards
(143 cards)
1
Q
Physiological mechanism of migraine
A
trigger event -> cortical spreading depression:
trigeminal nerve -> vasodilation and pain OR
inferior subcortex -> no aura OR
surface cortex -> aura
2
Q
Blood vessel abnormalities are a component of vascular headaches such as ________ and ________ headaches
A
migraine
cluster
3
Q
______ play a critical role in vascular headaches involving nerves
A
5-HT
4
Q
What does a low 5-HT level cause
A
migraine, it reduces urinary and platelet 5-HT w/ elevations in 5-hydroxyindole acetic acid during mirgraine
5
Q
Where are the 5-HT1B receptors located
A
endothelium of the micro vessels and mediate vasodilatory and contractile effects
6
Q
How does 5-HT receptors act in the meninges
A
block the release of inflammatory chemical
7
Q
How does 5-HT receptors act in the brainstem
A
block the pain impulses and central brain perception via trigeminal nerve
8
Q
Sumatriptan (5-HT1B receptor agonist) MOA
A
inhibits the release of calcitonin gene-related peptide (CGRP) which acts in the superior sagittal sinus following stimulation of trigeminal ganglion
9
Q
What are the 5-HT1B/1D agonists
A
Triptans
sumatriptan, zolmitriptan, naratriptan, rizatriptan
produce vasoconstriction
not for prophylatic treatment
10
Q
5-HT2 receptor antagonists
A
methysergide
used for prophylatic measure
11
Q
ADE of triptans
A
cardiac effects (vasospasm, myocardial ischemia, arrhythmias in pt with coronary artery disease)
pain at inj site
paresthesia, asthenia, fatigue, flushing, pressure in chest, neck, jaw, drowsiness, dizziness
12
Q
Triptans contrindications
A
pt with coronary artery disease, ischemia, or cerebrovascular disease
pt taking MAO-I
13
Q
How does ergotamine and caffeine help migraines
A
ergotamine: block NE reuptake and stimulates adrenergic receptors, activates serotonin pathways, reduces intracranial blood flow
caffeine: adenosine receptor antagonist
14
Q
Reyvow (lasmiditan) use in migraines
A
acute tx w/ or w/out aura not preventative
15
Q
Reyvow (lasmiditan) MOA
A
bind to 5-HT1F receptors, mediated by agonist effects at the receptor
16
Q
Reyvow (lasmiditan) ADE
A
dizziness, fatigue, burning or prickling sensation in the skin, sedation
serotonin syndrome
17
Q
Increased comorbidity with migraine
A
stroke, epilepsy, depression, sleep apnea, obesity, anxiety, pain disorders
18
Q
Pathophysiology of migraine headaches
A
vasodilation of intracranial extracerebral blood vessels -> activation of perivascular trigeminal nerves that release vasoactive neuropeptides
CGRP, neurokinin A, substance P
19
Q
Vasoactive neuropeptides promote ________ _________ around vascular structures in the brain -> pain
A
neurogenic inflammation
20
Q
Associated symptoms of central pain transmission that activate other brainstem nuclei
A
nausea, vomiting, photophobia, phonophobia
21
Q
Medications that can precipitate a migraine headache
A
antibiotics (tetracyclines, SMZ,TMP)
NSAIDs
bronchodilators (theophylline, pse)
GI (cimetidine, omeprazole)
CV (vasodilators, nitrates, dipyridamole)
Reproductive (estrogen)
22
Q
Clinical Presentation of migraine headache
A
common, recurrent, severe headache that interferes w/ normal functioning
23
Q
What is aura
A
complex of positive and negative focal neurologic symptoms that proceed or accompany an attack
evolves over 5 min and lasts less than 60 minutes
headache occurs w/in 60 min of the end of the aura
24
Q
Positive visual auras
A
scintillations (flash of light)
photopsia (perceived flashes of light)
teichopsia (transient sensation of bright shimmering colors)
fortification spectrum (zigzag banding of light)
25
Negative visual auras
scotoma (partial loss of vision or blind spot)
hemianopsia (blindness over half the field)
26
Sensory and motor auras
paresthesias or numbness in the arms and face
dysphasia or aphasia
weakness
hemiparesis
27
Symptoms of migraine headaches
recurring episodes of throbbing head pain. frequently unilateral, lasting 4-72 hours is left untreated
associated w/ n/v, sensitivity to light, sounds, movement
28
Diagnostic alarms for migraine headaches
acute onset of first or worst headache ever
accelerating pattern of headache following subacute onset
onset of headache after age 50
headache w/ systemic illness (fever, N/V, stiff neck, rash)
headache w/ focal neurologic sx or papilledema
new-onset headache in pt w/ cancer or HIV infection
29
Signs of migraine headaches
stable pattern, absence of daily headache
positive family history for migraine
normal neurologic examination
food and menstruation mat serve as triggers
improvement in headache w/ sleep
aura can signal migraine headache but not required for diagnosis
30
Diagnosis for migraine without aura
at least 5 attacks (POUND)
Pulsating
One day duration
Unilateral location
Nausea, vomiting, photophobia, phonophobia
Disabling intensity
31
Diagnosis for migraine with aura
at least 2 attacks
migraine aura fulfills criteria for typical aura
32
Diagnosis for typical aura
Full reversible visual, sensory, speech symptoms but no motor weakness
Visual symptoms including positive features or negative features, or unilateral sensory symptoms, or any combo
At least two:
1 sx that develops over 5 minutes
Each symptoms lasts for 5-60 min
Headache that meets criteria for migraine w/out aura begins during the aura or follows aura
33
Episodic vs chronic headache migraine
epi: 0-14 months MHD (monthly migraine headache days)
chronic: >15 months MDHs for at least 3 months where at least 8 are migraines
34
Goals for long-term migraine tx
reduce migraine frequency, severity, and disability
improve qol
prevent headache
educate and enable pt to manage their disease
reduce headache-related distress and physiological sx
35
Goals for acute migraine treatment
tx migraine attacks rapidly w/out recurrence
restore the pt ability to function
minimize the use of backup and rescue meds
optimize self-care for overall management
cost-effective in management
cause minimal or no adverse effects
36
What is medication overuse headache
frequent use of migraine med increase headache frequency
headache returns when med wears off leading to more meds
limit use to <10 d per month
37
When to consider preventative migraine therapies
recurring migraines that produce disability
frequent attacks occurring more than 2x per week
sx therapies are ineffective or contraindicated
pt preference to limit number of attacks
38
Max benefit of migraine meds is __ months while continuing med for ___ to ___ months with a gradual taper
6
6 to 12
39
nonpharm tx for migraine
ice
sleep in dark, quiet environment
exercise, eating habits, smoking cessation, limit caffeine
relaxation therapy
avoid triggers
40
Abortive tx (acute) start on onset of pain (not aura): NSAIDs/Analgesics
first line choice for mild-to-moderate attacks
Metoclopramide: speed absorption of analgesics and decrease migraine related n/v
Fioricet, Codeine: limit use, med overuse headache more common
41
Abortive tx (acute) start on onset of pain (not aura): Serotonin receptor agonist
Triptans
if one fails, pt can be switched to another
sumatriptan: 2 hr, SQ, oral, intranasal
Frovatriptan/Naratriptan: for patients with attacks of slow onset and longer duration
Lasmiditan: no heavy machines for at least 8 hr following dose
42
Triptans contraindications
h/o ischemic heart disease
uncontrolled HTN
cerebrovascular disease
pregnancy
43
When to supervise doses of triptans for patients
postmenopausal women
men >40 yo
uncontrolled CV risk factors
44
When to avoid triptans
w/in 24 hr of ergotamine derivatives
w/in 2 wks of MAO-Is
with SSRI or SNRI (serotonin syndrome)
45
Abortive tx (acute) start on onset of pain (not aura): Ergot Alkaloids and Derivatives
mod-to-severe attacks
ergotamine tartrate has more potent arterial effects than DHE
intranasal, IM, SQ, IV
46
Ergot Alkaloids and Derivatives contraindications
renal or hepatic failure
coronary, cerebral, or peripheral disease
uncontrolled HTN
sepsis
pregnancy (nursing)
47
Abortive tx (acute) start on onset of pain (not aura): CGRP receptor antagonists
when triptan is CI, ineffective, not tolerated
Ubrelvy
Nurtec ODT
Zavzpret nasal spray
48
Abortive tx (acute) start on onset of pain (not aura): Antiemetics
for n/v with migraines: single dose 15-30 min before oral abortive migraine med (metoclopramide, prochlorperazine)
migraines: alternative to narcotic analgesics
49
Abortive tx (acute) start on onset of pain (not aura): Opiate Analgesics
combo w/ codeine or tramadol w/ APAP are more effective
increase risk of medication overuse headaches
only for: mod-to-severe infrequent headaches when other therapies are CI
50
Abortive tx (acute) start on onset of pain (not aura): corticosteroids
rescue therapy (dexamethasone)
51
Abortive tx (acute) start on onset of pain (not aura): Valproate
mod-to-sever intensity (valproate)
52
Abortive tx (acute) start on onset of pain (not aura): magnesium sulfate
in migraine with aura (mag sul)
53
PPX pharm tx for migraine headaches: anti epileptic drugs
useful w/ cormorbid epilepsy, anxiety, bipolar illness
valproate/divalproex: get baseline LFT
topiramate: best use for pts
54
valproate/divalproex contraindications
pancreatitis and chronic liver disease
55
topiramate avoid/caution in what pt
kidney stone
cognitive impairment
56
PPX pharm tx for migraine headaches: antidepressants
amitriptyline: limit use in BPH and glaucoma, give in evening, orthostatic hypotension
venlafaxine: n/v, drowsiness, risk of 5-HT w/ triptan
57
PPX pharm tx for migraine headaches: antihypertensives
beta blockers: metoprolol, propranolol, timolol, good for HTN or angina
CCB: not in guidelines yet
58
Beta blockers caution for migraine headaches
AV conduction disturbances, asthma, diabetes
59
PPX pharm tx for migraine headaches: NSAIDs
naproxen has the best data
decrease frequency, severity, duration
GI/renal w/ prolonged use
prevent predictable headaches (menstrual)
give 1 wk prior to onset
cont for no more than 10 days
60
PPX pharm tx for migraine headaches: triptans
menstrual headaches
Frovatriptan for efficacy
give 1-2 d before expected onset
61
PPX pharm tx for migraine headaches: CGRP inhibitors
for episodic and chronic migraines
monoclonal antibodies: given IV or SQ
receptor antagonists: gepants given ODT
Nurtec for preventative or acute care
Atogepant only for prevention
62
PPX pharm tx for migraine headaches: Onabotulinumtoxin A (botox)
for pt >15 headache days per month w/ inadequate response to at least two:
topiramate
divaloprex, valproate
beta-blocker
TCA
SNRI
given 155 units over 30 sites every 12 wks
63
Consider ppx tx when what
recurring migraines produce significant disability
frequent attacks occuring more than 2x/wk
sx therapies are ineffective or CI
pt preference to limit number of attacks
64
Tension-type headache epidemiology
infrequent: <1 episode/month
frequent: 1-14 days per month
risk factors: coexisting migraine, depression, anxiety, poor stress management
65
Tension-type headache pathophysiology
pain from myofascial and peripheral sensitization of nociceptors
66
Tension-type headache clinical presentation
mild-mod pain
dull, non-pulsatile tightness or pressure
bilateral
mild photophobia or phonophobia
67
Tension-type headache nonpharm tx
stress management, relaxation, biofeedback
68
Tension-type headache pharm tx
analgesics +/- cffine and NSAID
combo analgesics: no more than 10 d/month
NSAID: no more than 15 d/month
TCA may be prescribed
maybe: topiramate, gabapentin, tizanidine
69
Cluster headache epidemiology
4:1 male to female, in 20-30 yo
h/o smoking
unilateral pain that occur in series lasting for weeks-months (clusters) remission periods last months-years
70
Cluster headache pathophysiology
neuroimaging of hypothalamus
71
Cluster headache clinical presentation
hallmark: circadian rhythm of painful attacks
daily x 1wk to several months
average remission is 2 years
common at night in spring/fall
pain lasts 15-180 minutes
excruciating, penetrating, boring, lacrimation, nasal stuffiness, rhinorrhea, miosis
72
Cluster headache abortive tx
oxygen: facial mask
triptans: SQ, intranasal
72
Cluster headache abortive tx if first line does not work
ergotamine derivatives: DHE bolus over d to wk, tartrate sublingually
intranasal lidocaine: no systemic side effects
73
Cluster headache ppx tx
verapamil (2-3 wk before benefit, first line)
lithium (caution renal, CV, dehydration, pregnancy)
galcanezumab (for pt with headache >1 month who failed primary agents)
corticosteroids (5 d prednisone high dose then taper)
74
Alzheimer is a gradual progressive dementiathat affects what
cognition, behavior, and functional status
75
Alzheimer etiology
65 and older highest risk
can be 30 and still have it
survival is 4-8 years after diagnosis can live 20 years with
most common death is pneumonia due to swallowing difficulties and immobility in terminal stage of disease
76
Alzheimer etiology of early onset <60 yo
error in protein binding
mutation in presenilin 1 on chromosome 14, APP on chromosome 21, presenilin 2 on chromosome 1
increases amyloid beta in brain causing oxidative stress, neuronal destruction, and clinical syndrome
77
Alzheimer etiology of late onset
APOE gene on chromosome 19
carriers of >2 APOE4 alleles have higher risk and earleir onset
78
Other factors of Alzheimers with increased risk
increase ages
women
decreased reserve capacity in the brain
head injury
down syndrome
depression
mild cognitive impairment
vascular disease
79
Alzheimer pathophysiology
tangles
plaques
Ach
glutamine
cholesterol
estrogen (not really)
80
General presentation of Alzheimer
vague memory "forgetful"
cognitive decline is gradual
behavioral disturbances present in moderate stages
loss of daily fx
81
Sx of Alzheimer
cognitive:
memory loss, aphasia, apraxia, agnosia, disorientation
neuro:
depression, aggression, wandering
functional: inability to care for self
82
Rule out what before Alzheimer
Vit B12 deficiency, hypo/hyperthyroidism, anemia, electrolyte imbalance, renal/hepatic dysfunction, syphilis, HIV
83
Diagnostic test for Alzheimer
CT or MRI
84
What is the primary clinical diagnosis for Alzheimer
cognitive decline, loss of social or occupational fx
PET: flortaucipir F18 (estimate tau protein tangles)
85
MMSE classifications
Mild: 26-21 (withdrawal from tasks)
Moderate: 20-10 (suspicious or tearful)
Severe: 9-0 (no speak or walk)
86
What meds to disc for pt w/ Alzheimer
benzos, sedative hypnotics, anticholingerics, antipsychotics
H2RA, corticosteroids, opioids
87
Nonpharm tx for Alzheimer
avoid environmental triggers
redirect pt environment
calm place, exercise, light therapy, music, relax, massage
88
What is considered successful tx of Alzheimer
decline of <2 points per year on MMSE
89
Pharm tx for Alzheimer: cholinesterase inhibitors MOA
goal to enhance cholinergic activity
donepezil: reversibly inhibit AChE (ODT, patch, tablet)
rivastigmine: pseudo-irreversible inhibit butyryl and AChE (cap, patch)
galantamine: selective reversible AChE inhibitor, enhance nicotinic receptors (tab, ER cap, soln)
90
Dosing considerations for rivastigmine and
if interrupted for several days pt should restart on lowest dose, take with food
91
When switching from one cholinesterase inhibitor to another how long do you have to wait
donepezil to another: 7-14 d
from rivastigmine or galantamine: 1-2 d
do not combo drugs together
92
When to use Namenda for Alzheimer
mod to severe AD
block glutamatergic neurotransmission by antagonizing NMDA receptors
(soln, tab, ER cap)
93
Role of combo therapy for Alzheimer
mod-to-severe AD
memantine + donepezil (namzaric)
94
Use of Monoclonal Antibodies for Alzheimer
directed against aggregatted forms of amyloid beta
assist in reducing formation and appearance of plaques
95
What are the
aducanumab
lecanemab
donanemab
96
Monoclonal Antibodies for Alzheimer ADE
fever, chills, urticaria
ARIA (cerebral edema, hemorrhages)
should do regular MRI
97
Take home points for Monoclonal Antibodies for Alzheimer
not for severe stages of AD
further trials are needed to investigate whether reducing plaques correlates w/ clinical meaningful changes in cognition
98
Dietary supplements for Alzheimer
Ginko Biloba: 240 mg/d, avoid in anticoagulant, anti platelet therapy, caution with NSAID
Prevagen: is not good
99
What is the pathophysiology of parkinson's disease
degeneration of the pars compacta of the substantia nigra, leading to overactivity in the direct pathway
100
What are the primary treatment compounds of parkinsons disease
increase dopamine synthesis
decrease dopamine catabolism
stimulate dopamine receptors (agonists)
101
What are the secondary treatment compounds of parkinsons disease
antagonize muscarinic cholinergic receptors
enhance dopamine release
NMDA glutamine receptors
102
Levodopa/Carbidopa (sinemet) MOA
levodopa is the immediate metabolic precursor of dopamine which crosses the BBB (decarboxylation to dopamine)
carbidopa is a peripheral dopa-decarboxylase inhibitor
103
The absorption of levodopa in the intestine and at the BBB is mediated by a saturable _____ ______ transporter
amino acid
104
Levodopa/Carbidopa (sinemet) DDI
pyridoxine (vit B6) enhances the extracerebral metabolism of levodopa
105
Entacapone (comtan) and tolcapone (tasmar) MOA
entacapone is a peripherally acting inhibitor of catechol-O-methyltransferase (COMT)
tolcapone is a central and peripheral inhibitor of COMT
(they prolong the action of levodopa by diminishing metabolism)
106
Metabolism of L-dopa
peipheral and central metabolism depicting the sites of action of enzyme inhibitors. AAAD, AD, COMT, MAO
107
Selegiline MOA
selective inhibitor of MAO-B and at higher doses it does MAO-A
enhances and prolongs the antiparkinson effect of levodopa
108
Rasagiline MOA
selective inhibitor of MAO-B (more potent than selegiline)
used as a neuroprotective agent and for early symptomatic tx
109
Can you combine MAO-B and MAO-A with levodopa
NO, this may lead to a hypertensive crises dir to peripheral NE
110
Bromocriptone and Pergolide (ergot) MOA
Bromocriptone partial D2 agonist
Pergolide parial agonist for D1 and D2 receptors
can be combined with levodopa
111
Pramipexole and Ropinirole (non-ergot) MOA
first line in initial tx of PD
Pramipexole: affinity for D3 (may neuroprotect)
Ropinirole: D2 receptor agonist
112
Benztropine and Trihexyphenidyl MOA
anticholinergic drugs decrease the excitatory actions of cholinergic neurons in the striatum
may improve tremor and rigidity
113
Amantadine (symmetrel) MOA
may potentiate dopaminergic function by increasing the synthesis of release of dopamine or inhibition of dopamine reuptake
may improve bradykinesia, rigidity, tremor
114
Apomorphine (apokyn) MOA
non-narcotic derivative (activate D1 and D2 receptors)
temp relief of off-periods of akinesia
115
What are the 4 hallmark features of parkinsons disease
Tremor at rest
Rigidity
Akinesia/bradykinesia
Postural instability
116
What is the hallmark sign of parkinsons on a cellular level
degeneration of dopaminergic neurons projecting from the substantia nigra pars compacta to the striatum
117
Environmental factors which elevate and lower risk of parkinsons
elevate: chronic exposure to pesticides
lower: caffeine and cigs
118
Diagnosis of parkinsons disease
presence of bradykinesia + tremor, rigidity, or postural instability
exclude other types of tremor disorders
presence of 3 supporting criteria
119
What are the supporting criteria for parkinsons disease
asymmetry of motor signs
unilateral onset
progressive disorder
resting tremor
response to carbidopa/l-dopa
L-dopa response for >5 yr
presence of L-dopa dyskinesia
120
Goals of parkinsons therapy
improve motor and nonmotor symptoms
maintain QOL
preserve daily activities, improve mobility, no ADEs
121
nonpharm therapy for parkinsons
surgery:
diagnosis of L-dopa-responsive PD
absence of cognitive impairment
Deep brain stimulation (DBS) which targets thalamus
122
When to use anticholinergic meds (benztropine and trihexyphenidyl) in parkinsons
increase striatal cholinergic activity
good for tremor
avoid: advanced age, pre cognitive deficits, dysphagia
123
When to use amantadine-1 in parkinsons
inhibit NMDA receptors
manages L-dopa-induced dyskinesia
manages tremor, rigidity, bradykinesia
DO NOT rapid w/drawal
124
ADE of amantadine-1
livedo reticularis
-mottling of the skin
-upper and lower extremities
-w/ lower edema
125
When to use carbidopa/levodopa in parkinsons
symptomatic PD
25/100 TID initial
DO NOT rapid w/drawal
126
What are the formulations for carbidopa/levodopa
ODT
capsule (can sprinkle on food)
comes in IR and ER
127
What are the 4 motor functions of L-dopa
end-of-dose wearing off
delayed on or no on response
freezing
dyskinesia
128
How to treat end of dose wearing off L-dopa effect
increase frequency of dose
add istradefylline, COMT, MAO-B, or dopamine agonist
rapid: apomorphine SC or L-dopa powder for inhalation
overnight: HS admin of dopamine agonist or formulations that provide
129
How to treat delayed on effect L-dopa effect
give carbidopa-L-dopa on empty stomach
use ODT carbidopa-L-dopa
avoid SR
use apomorphine SC or L-dopa inhalation
130
How to treat freezing L-dopa effect
increase carbidopa-L-dopa dose + dopamine agonist or MAO-B inhibitor
physical therapy or walking assist devices
131
How to treat dyskinesia L-dopa effect
provide smaller doses of carbidopa-L-dopa
reduce dose of adjunctive dopamine agonist
add amantadine
132
When to add MAO-B inhibitors in parkinsons
cause prolonged dopaminergic activity
DDI: SSRI, meperidine, other opioid analgesics
133
Selegiline (MAO-B) for parkinsons
early PD: improve motor functions
advanced PD: adjunctive for "wearing off"
may worsen dyskinesias
134
Rasagiline (MAO-B) for parkinsons
early PD: effective as monotherapy
advanced PD: add-on therapy for motor fluctuations
135
Safinamide (MAO-B) for parkinsons
advanced PD: adjunctive to carbidopa/L-dopa for wearing off
136
When to add COMT inhibitors for parkinsons (entacapone, tolcapone, opicapone)
extend effects of L-dopa
manages wearing off
entacapone: need to give w/ every L-dopa
tolcapone: fatal hepatotoxicity check ALT/AST
opicapone: qd dose
137
When to use dopamine agonist for parkinsons
stimulate D1, D2, D3
monotherapy for mild-mod PD
adjunct to L-dopa to reduce off time
138
When to use dopamine agonist for parkinsons: younger pt, older pt, cognitive problems or dementia
younger pt: dopamine agonist over L-dopa
older pt: use conservatively
cognitive problems or dementia : AVOID
139
less common but serious ADE of dopamine agonist
impulsive and compulsive behaviors
hallucinations and delusions
140
When to use apomorphine in parkinsons
SC inj
can cause hypotension
advanced PD w/ intermittent off episodes
141
When to use adenosine receptor antagonist in parkinsons
Istradefylline
for off episodes
142
Monitoring for PD
med admin times
inquire specifically about dose-by-dose effects of med
