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TPX Neuro, Psych, & Sub abuse > Week 5: MS, Headache > Flashcards

Week 5: MS, Headache Flashcards

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1
Q

What is a Primary Headache disorders

A

Not due to/related to other medical condition

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2
Q

Primary Headache Disorders: Migraine

Epidemiology

A

women>men

~12% of the population
second most disabling

condition globally

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3
Q

Primary Headache Disorders

Migraine W.O aura Diagnostic criteria

A

per internatinal classification of headache disorders 3r edition (ICHD-3)

A)atleast 5 attacks fulfilling critera B-D

B)Headache attacks lasting 4-72hrs (when untreated or unsuccessfully treated)

c) headache has atleast 2 of the following 4 characteristics
*unilateral location
*pulsating quality
*moderate or severe pain intensity
*aggravation by or causing avoidance of routine physical activity (e.g walking or climbing stairs)

D. during headache at least 1 of the following.
*nausea and/or vominting
photophobia or phonophobia

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4
Q

Primary Headache Disorders

different phases of migraines

A
  1. Premonitory (hours to days)
    *tiredness
    moodchange
    yawning
    thirst
    cravings
    urinary frequency
    light and sound sensitivity
    cranial autonimoic symptoms:conjunctival infection
    tearing
    rhinorrhoea,flushing and sweating

2.Aura phase

3.Headache Pain Phase (4-72 hrs)
*throbbing headache
*n&V
*light, sound and smell sensitivity

4.Post drome(up to 48hrs)
*tiredness
*difficulty concentrating

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5
Q

Primary Headache Disorders

Migraine patho

A

Premonitory phrase (prodrome): hypothalamus and other areas of brain triggered by alterations in homeostasis
*increased parasympathetic activity activates meningeal nociceptors

aura phase: cortical spreading depression

Headache pain phase: neuropeptides
cortical spread depression
sensitization
neuronal hyperexcitability

Seretonin

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6
Q

Primary Headache Disorders

Migraine triggers

A

stress

hormone changes/ menstruation

not eating

weather

sleep disturbance

perfume/ odor

neck pain

bright lights

alcohol

smoke

sleep late

heat

food

exercise

sexual ativity

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7
Q

Primary Headache Disorders

Migraine with aura diagnosis

A

Per ichd-3

A) atleast 2 attacks fulfilling criteria b and c

B) one or mor eof the following fully reversible aura symptoms

*visual
*sensory
*speech and/or language
*motor
*brainstem
*retinal

c)ateast 3 of the folloring 6 characteristics

*atleast 1 aura symptom spreads gradually over>5 min
*2 or more aura symptoms occur in succession
*each individual aura symptom lasts 5-60 min
atleast 1 aura symptom is unilateral
atleast 1 aura symptom is positive
the aura is accompanied, or followed within 60 min by headache

Visual»sensory>language

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8
Q

Primary Headache Disorders

Migraine vs TIA

A

migraine
*positive visual symptoms(may be followed by vision loss)
*gradual onset/evolution
*subsequential progression
*repetitive attacks of identical nature
*flurry of attacks midlife
*duration < 60 min
*headache follows ~50%

TIA
*visual loss
*abrupt onset
*simultaneous occurrence
*duration <15 min
*headache accompaniment uncommon

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9
Q

Primary Headache Disorders

General Migraine acute pharmacotherapy principles

A

abortive treatments are usually more effective if they are given early in the course of the headache

a large single dose tends to work better than repetitive small doses

counsel pts.on med overuse headache

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10
Q

Primary Headache Disorders

summary of acute migraine options for..

a)mild-mod. migraine attacks

b)mod.-severe migraine attacks

c)refractory mod-severe

A

a) mild-mod.
non opioid analgesics

NSAIDS
acetaminophen
ceffeinated analgesics combos

b)mod-severe
MIGRANE SPEC. AGENTS
*triptans (geenrally preffered over dha)
DHE
gepants(rimegepant, ubrogepant) or ditans (lasmiditan) can be considered if triptans are contraindicated or not tolerated

c)refractory
*combos of triptains+nsaids
*gepants
*ditans
*combos of analgesics w. codeine or tramadol can be considered, infused infrequently (not recommended for regular use)
*opioids (not recommended for regular use)

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11
Q

Primary Headache Disorders

General Considerations for NSAID use in Migraines

A

*acute treatment for mild-moderate migraines

*all nsaids are effective in migraine treatment

*can be combined w. triptans for more severe cases

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12
Q

Primary Headache Disorders

NSAIDs specifically indicated for migraines and considerations

A

Diclofenac Potassium oral solution (Cambia)
*indicated for migraine w. or w.o aura in >/=18 y.o
*must be added to 1-2 oz or 2-4 tbsp of water prior to administration

Celecoxib oral solution (Elyxyb)
*indicated for acute migraine treatment w. or w.o aura in adults

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13
Q

Primary Headache Disorders

Bubalbital/APAP/Caffeine (Fioricet, Bac, Esgic, Zebutal) considerations

A

non controlled substance

indication: tension -type headache, but also used in migraine

*reserved as a last resort for abortive migraine treatment

*CAN CAUSE MEDICATION OVERUSE HEADACHE IF USED MORE THAN 5X PER MONTH. limit use to </=3x per month

1 tablet/capsule contains:
50 mg butalbital
*300-325 mg APAP
*40 mg caffeine

*AE: CNS depression, stomach upset

BBW: hepatotoxicity (APAP)

available as oral solution (Vtol LQ), formulation w.o caffeine (Allzital, Bupap), and formulation w.c codiene (Fioricet/codeine: CIII)

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14
Q

Primary Headache Disorders

Butalbital/ASA/Caffeine considerations

A

CIII
indicated for tension type headache, but also used in migraine

CAN CAUSE MEDICATION OVERUSE HEADACHE

1 tablet/capsule contains:
50 mg butalbital
325 mg ASA
*40 mg caffeine

AE: cns depression, stomach upset

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15
Q

Primary Headache Disorders

Triptans

indication:
mao:
AE:
caution:
CI

A

indications: acute treatment of mod-severe migraine

MOA: 5HT1D AND 5-HT1B selective agonists. causes vasoconstriction and reduces neurogenic inflammation associated with antidromic neuronal transmission correlating with relief of migrating.

AE: flushing, chest pain, palpitations, dizziness, fatigue, xerostomia, serotonin syndrome

caution: in older adults

CI: hemiplegic migraines or mibrain w. brainstem aura, known or suspected ischemic heart disease
*Woldd-parkinson-white syndrome or arrythmias
cerebrovascular syndromes (stroke-TIA)
*uncontrolled HTN
*use w.i 24hrs of an ergotamine prep or a different triptain
MAO-Is.

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16
Q

Primary Headache Disorders

Triptans considerations

A

first line treatment in acute mod-severe migraines

administer earlr in the course of a migraine attack to improve response

limit use <10 days /month to avoid med overuse headache

*Avoid use in pts. w. high risk of cardiovascular events

*SQ

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17
Q

Primary Headache Disorders

Individual Triptan considerations

A

Almotriptan:
*

Eletriptan (Relpax):
*CI w. potent cyp3a4 inhibitors. do not adminster w.i 72hrs of cyp3a4 inhibitors (ketoconazole, nefazadone, clarithromycin, ritonivir)
*higher lipophilicity into brain

Frovatriptan (Frova)
*PO
*longest half life, may cause in prevention of migraines

Naratriptan (amerge)
*second longest t 1/2

rizatriptan
*PO,ODT

Sumatiptan
*PO
*intranasal formulation (15-30 min onset )
*SQ: 10 min onset
*AE occurs in 40% of pts. such as chest tightness and pressure, sob, PALPITATIONS, and anxiety after SQ. occurs shortly after and resolved w.i 30 min.
*try diff triptan if sumatriptan is intolerable

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18
Q

Primary Headache Disorders

Lasmiditan (REyvow)

A

controle substance : CV

indication: acute treatment of migraine w. or w.o aura in adults

moa: 5HT1F receptor agonists
dose: 50-200 mg once/day

AE: cns depression, seretonin syndrome, decreased HR, increased BP, palpitaions, dizziness, n&V

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19
Q

Primary Headache Disorders

Lasmiditan considerations

A

can cause profound cns depression

must wait atleast 8 hrs between dosing and operating heavy machinery or driving

currently a brand name so expensive

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20
Q

Primary Headache Disorders

Rimegepant(Nurtec) considerations

A

class: GEPANTS

moa: small molecule CGRP antagonists

indication: acute AND preventative treatment of migraines in headaches

Dose:PO ODT
*acute treatment: 75 mg PO qd: MDD 75mg
*prevention: 75 mg PO every other day

*AE: abdominal pain, dyspepsia, nausea

avoid use in Crcl<15mL/min

avoid use in severe hepatic impairment*onset of acion</= 2 hrs for acute treatment

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21
Q

Primary Headache Disorders

Ubrogepant (Ubrelvy) considerations

A

class: GEPANTS

moa:

indication: acute treatmnt of migraine w. or w.o aura in adutls

dose: 50 to 100 mg PO once. if persist, may repeat sode >/= 2 hrs/ mdd 200MG

AE: nausea, drowsiness, xerostomia

ci: strong CYP3A4 inhibitors

dose reduction in Crcl<30mL/min, avoid use in Crcl <15 ml/min (not studied

*do not eat with a highfat meal, delays absoprtion

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22
Q

Primary Headache Disorders

anti-migraine ergot class considerations

A

Examples: dihydroergotamine and ergotamine

MOA: activation of 5HT1D and 5HT1B receptors on the intrcranial blood vessels-> vasoconstiction
or acivation of 5HT1D receptors on sensory nerve endings of the trigeminal system-> inhibition of pro-inflammatory neuropeptide release

BBW: CI w.potent cyp3a4 inhibitors including protease inhibitors, macrolide abx, and azole antifungals

Serious AE: cardiac valvular fibrosis, ergotism, seretonin syndrome

AVOID USE IN PREGNANCY OR BREASTFEEDING

DO NO use w.in triptans, other seretonin agonists, or ergotamine containing or ergotamine like agents

monitoring: renal and liver function

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23
Q

Primary Headache Disorders

Ergotamine considerations

A

indication: acute trtmt of mod-severe migraine

other migraine trtments preffered unless

SL tabs

not recommended for use in older adults

AE: N&V, ecg changes, HTN, ischemia, vasospasm, numbness, paresthesia, gangrene, etc.

pearls: d/c after limited use can rsult in rebound headaches

grapejuice can increase ergotamine levels

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24
Q

Primary Headache Disorders

Dihydroergotamine (DHE) considerations

A

indications:
injection: acute treatment of cluster headaches
injection and nasal spray: acute treatment of migraine headaches w. or w.o aura

offlabel indicaions: medication overuse headache, status migrainosus

fewere AE than ergotamine

formulations; intranasal, injection (IV, IM,SQ)

CI: ischemic heart disease, vascular surgery,
nasal spray ci w. hemiplegic migraine or migraien w. brainstem aura.
use w.in 24hrs of triptan or other ergotamine preparation

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25
Primary Headache Disorders inpatient migraine treament
IV dexamethasone SQ sumariptan iv PROCHORPERAZINE OR metaclopramide OR chlorpromazine + diphenhydramine (combos of thes emore effective than SQ sumatriptan) iv dhe+ANTIEMETIC iv valproate iv/im KETOROLAC iv MG
26
Primary Headache Disorders opioids and barbiturates in migraine treatment
avoid opioids and barbiturates for acute or preventative migraine treatment can increase risk for dependence, addiction, or medication overuse headache however can be lmited to use in pts. w. ci to other meds or in refractory pts.
27
Primary Headache Disorders Preventative migraine treatment consideration
consider if.. attacks significantly interfere w. pts dail routines frquent attacks CI to failure or overuse of acut treatments AE w. acute treatments pt. preference
28
Primary Headache Disorders Topiramate
indication: labeled: prevention of migraine headache in pts >/=12 y.o off label: prevention of cluster headache MOA: block voltage depdendant sodium channels enhances GABA activity antagonizes AMPA/ kainate glutamate rceptors weakly inhibits carbonic anyhrase AE:cognitive dysfunction, cns defects, nephrolithiasis, metabolic acidosis, angle closure glaucoma, aligohidrosis/hypothermia, suicidal ideation, weightloss, paresthesia COUNSEL ON IMPORTANCE OF HYDRATION AVOID IN PREGNANCY
29
Primary Headache Disorders Valproic Acid considerations
moa: increases GABA or may enhance action of GABA AE: cns effects, hematologic effects, hepatotoxicity, encephalopathy, TEN, SJS, DRESS *BBW hepatotoxicity, patients w. mitochondrial disease, fetal risk, panceatitis ci: PRVENTION OF MIGRAINE IN WOMEN AND WOMEN OF CHILDBEARING AGE WHO ARE NOT USING EFFECTIVE contraception
30
Primary Headache Disorders beta blockers
propanolol, timolol specifically indicated for migraine prevention moa: in migraine unknown. several different theories. prop. and tim. have high affinity for 5HT2B and 5HT2C receptors and higher cns penetration inhibit nitrous oxide production
31
Primary Headache Disorders Tricyclic Antidepressants
Amitrityline (tertiary), (nortriptyline (secondary) BWW: suicidality moa: increases the synaptic concentration of seretonin and/or norepinephrine in the CNS by inhibitino of their reuptake by presynaptic neuronal mebrane pump considerations: lower initial doses for migraine prevention than for MDD AE: antihcolinergic, cardiac conduction abdnormalities, orthostatid hypotension, seretonin syndrome
32
Primary Headache Disorders Venlafaxine
BBW: suicidality MOA: SNRI AE: CNS depression, weightloss, anorexia, increased bp, hepatotoxicity , hypnatremia, acute angle closure glaucoma, seretonin syndrome adequate trial 1-2 mo. at therepeutic dose
33
Migraine secific Treatments Atogepant (Qulipta)
clas: Gepant PO tab indication:PREVENTATIVE treatment of episodic migraine in adults not recommended in severe hepatic impairment AE: constipation, nausea, drowsiness, fatigue, weightloss.
34
Migraine Specific Treatments CGRP monoclonal antibodies considerations
long half life: 28-32 days caution in recent cv or cerebrovascular ischemic events few drug interactions: efgartigimod
35
CGRP monoclonal Eptinezumab (VYEPTI) considerations indication: Target Admin: adequate trial time: AE:
CGRP monoclonal indication: prvention of migraines Target: CGRP ligand Admin: IV q 3 mo. adequate trial time: 6 mo. AE:infusion reaction nasopharyngitis nausea
36
CGRP monoclonal Erenumab(AIMOVIG) considerations indication Target Admin: adequate trial time AE:
CGRP monoclonal indication: prvention Target: CGRP receptor Admin: SQ q mo. adequate trial time: 3 mo. AE: injection site reaction constipation
37
CGRP monoclonal Fremanezumab (AJOVY) considerations indication Target: Admin: adequate trial time: AE:
CGRP monoclonal Fremanezumab (AJOVY) considerations indication: prevention of migraines Target: CGRP ligand Admin: SQ q mo or q3mo (dosing dffers) adequate trial time: 3 mo. for q mo. or 6 mo. for qurterly dosing AE: injection site reaction
38
CGRP monoclonal Galcanezumab considerations indication Target: Admin: adequate trial time: AE:
CGRP monoclonal indication: prevention of cluster headache during cluster. prvention of migraines Target: CGRP ligand Admin: sq q mo. (dosing differs on indication) adequate trial time: 3 mon. AE: injection site reactions
39
Peripheral nerve blocks
intramuscular injections containing lidocaine and/ or bupivacaine and/ or methylprednisolone indication: migraine cluster headaches hemicrania continua and other headache disorders ae: pt may report lightheadnessess or dizeeiness after injection anesthetic nerve blocks safe in pregnancy, corticosteroid injec. not safe
40
nonpharm/ alternative migraine treatments
stress reduction techniques dietatry changes trigger avoidance magneseium vit. b2 (riboflavin feverfew butterbur neuromodulation devices
41
FDA approved noninvasive neuromodulation devices
acute treatment of migraine w. or w.o aura >/= 12. savi DUAL Nerivio/ Theanica gamma core/electrocore >/= 18. y.o relivion mg/neurolief cefaly dual enhanced cefaly/ preventative: cefaly dual enhanced gamma core
42
Migraine Preventative therapies and considerations PO Mg
indication: PPX esp. in migraine esp. w. aura PO F of mg citrate? mg oxide AE: diarrhea, N&V
43
Migraine Preventative therapies and considerations Vit. b2 Riboflavin
migraine ppx well tolerates
44
Migraine Preventative therapies and considerations feverfew
migraine ppx avoid use in pregnancy may cause uterine cntractions and abortions ae: gi. can counsel pts to titrate slowly
45
Migraine Preventative therapies and considerations butterbur (Petasites)
migraine PPX avois productz tht are not labeled as free from pyrrolizidine alkaloids (PA-free)
46
Dx of chronic migraine
migraines on >/= 15 days /months for > 3 mo.
47
Chronic Migraine Pharm treatment considerations Onabotulinumtoxin A (Botox)
neurotixin that prevents calcium dependent release of ach and produces a sttae of denervation BBW: spread of toxin effect AE: injection site pain, neck pain, myalgia, facial paresis
48
Menstrual migraine treatments
migraine occuring day 1_/- 2) of menstruation can be due to flucuating estrogen treatments: *frovatriptan (lonh half life): continue 6 days total Naratriptan: continue for 6 days others includ... Colmitriptan Mg AVOID ESTROGEN CONTAINING CONTRACEPTIVES IN MIGRAINE W. AURA PTS
49
considerations for contraceptives in migraines
2-2.5 x greater risk in females w. migraines w. aura estrogen increases risk of ischemic stroke and should be avoided by woen w. migraine w. aura who already have an increased stroke risk
50
migraine treatment for pts with cv or cerebrovascular diseases
gepants lasmiditan
51
Acute migraine trtment for pregnant pt
first line: apap avoid NSAIDS in 3rd semester
52
Tension headaches characteristics
last 30 min-7 days atleast 2 of the following of 4 characteristics bilateral pressing or tighening pulsating quality mild or mod intensity not aggrvated by routine physical ctivity such as walking or climbing stairs no more than 1 of photophobia, phonophobia, or mild nausea neither modrate, severe, nor vomiting
53
Tension type headache treatment acute: preventative
acute: simple analgesics (NSAIDS, apap) combo analgesics w. caffeine (more effective then alone) not preffered alternaitve: butalbital, venlafaxine COUNSEL PT ON MED OVERUSE HEADACHE Preventative: AD: TCA's, mirtazipine, venlafaxine anticonvulsants: gabapentin, topiramate trigger point injections
54
Cluster Headache characterizations
severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 min when untreated atleast 1 of the following signs or symtoms conjunctival infection and or lacrimation nasal congestion and/or rhinorrhea eyelid edema forhead facial sweating miosis and or ptosis occur with a frequency btw 1 q other day and 8 per day
55
cluster headache etiology
prevalence <1% male> female onset 20-40 y.o risk factors: genetics tobacco use h/o head trauma
56
acute treatment of cluster headache
oxygen sq (preferred)or intransal(alternative) sumatriptan intransal zolmitriptan
57
preventative cluster headache treatment
verapamil (gold standard) glucocorticoids galcanezumab lithium topiramate greater occipital nerve blocks
58
hemicrania continua
unilateral headache that will not subside present for >3 mo. on same side of headache... conjunctival infection and or lacrimation nasal congestion and/or rhinorrhea eyelid edema forhead facial sweating miosis and or ptosis must respons absolutely to indomethacin
59
hemicrania continua trt
indomethacin gold standard alternatives:onabotulinumtoxin A occipital nerve stimulation vagus nerve stimulation peripheral nerve blocks
60
TRamatic brain injury headache what is it
resembles clinincal features of migraines and or tension type headaches associated w. postocncussive SS-fatigue, dizziness, insomnia, conc impairment, seizures, depression, anxiety onset headache w.in 7 days if trauma
61
pseudotumor cerebri
increased intracranial pressure causeing headache, papilledema, vision loss effects women primarily of child bearing age maybe med induced: growth hormone, tetracyclines, retinoids trt: withdraw offending agent weightloss carbonic anhydrase inhibitors (Acetazolamide, topiramate) furosemide migriane preventative medications
62
brain tumor headache
varying features dependent on tumor and type location common phenotype is tension type headache pain may be bilateral or on the side of the tumor associated neurologic symptoms: seizures, fatigue, cognitive dysfunction, focal weakness
63
brain tumor headache red flags
acute new usualy severe headache or headache tjay has changed from precvious patterns new headache onset in an adult espin 50 y.o an dup headache in older adults or in children headahce one xertion onset at night or onset at early morning headahce that is progrssive in nature headache s.w fever or other systemic symptoms headache w. meningismus headache w. neurologic signs precipiation of head pain with valsalva maneuver (by coughing, sneezing, or bending over
64
RCVS (reversible multifocal narrowing of the cerebral arteries)
thunder clap headaches neurologic deficits r/t brain edema, stroke, or seizure meds associated w. it ssri triptans ergots cyclophsophomide tacrolimus nasal decongestants illegal drugs others
65
subarrachnoid hemmorhage
sudden or thunderclap onset of headache worst headache of my life nausea comiting neck stiffiness focal neurologic defecits brief loss of conciousness LIFE THREATENING EMERGENCY
66
MEdication overuse headache
increased excitability of neurons in the cerbral cortex and trigeminal sysstem vicious cycle of over use, more headaches, more medication
67
Dx of medicaiton overuse headache
heaache occuring >/= 15 days/ month w. a pt with a preexisting headahce disorder regular overuse for >3 mo. of one or more drugs that can be taken for acute and/or symptomatic trt
68
medication over use headache risks for medicatoins
anti-'migraine ergots >/= 10 days per month triptans: 10 days/ month opioids >/= 10 days per month non opioid analgesics >/= 15 days / month butalbitlal >/= 5 days per month: WORSE OFFENDER
69
trt of medicaiton overuse headache
d/c / wean off overused headache may consider bridge therapy during the initial period after d/c of overused medication initiate preventative w. prn breakthoruh therapy
70
substance withdrawal headache
caffeinw withdrawal headache: caffeine >200 mg/day for ?2 eeks opioid wthdrawal headhache: opioids > 3 months and many more estrogen TCA's SSRI
71
Headahce hx and red flags
DO NOT OVERLOOK POTENTIALLY SERIOUS, LIFE THREATENING CAUSES OF HEADACHE family hx , caffeine/ alcohol consumption, occupation, medical hx, current meds (frequency of NSAID use, etc) hx: how lon ghav ethey been occuring location: wheres is the pain and how does it radiate frequency: how often do headaches occur duration: how long does pai nlast severity: how severe is the pain type: what type of pain is it triggers: any factors that precipitate and or worsen headache accompanying symtpmos: any other symptoms accompany headache significance: what impact does headache have on activities of daily living relieveing factors- what relieves the headaches
72
headache red flags: SNOOP
Systemic SS ex: fever mylagias, weightloss Systemic Disease ex: malignancy, acquired immune deficiency syndrome Neurologic symptoms/signs Onset sudden (thunderclap headache) onset after 40 years Pattern change (progressive headache w. loff os ehadache free periods, chanhge in type of headache)
73
MS
chronic autoimmune inflammatory disease that causes demyelantion of cns nerves
74
etiology of MS
ENVIRONMENTAL+GENETIC Environmental *EBV *Human Herpes Virus-6 Genetic *HLA DR-2 (mutation) * XX female (20-40 yo)
75
PATHO OF MS
mutation / polymorphism in HLA DR-2 causes exaggerated autoimmune response when exposed to an antigen (such as viruss) when T helper cell phagocytoses and presents part of antigen... it crosses the BBB, eventually binding to oligodendrocytes (oligodendrocytes myelainate axons in CNS) interactions w. oligodendrocytes causes increase in inflammatory markers (IL1, IL6, TNFa) which act on epithelial cells on BBB. causes endotghelial cells to increase expression of WBC adhesion markers to inrease wbcs in area 2. causes vasodilation in bbb 3. increase capillary permeability between endothelial cells 4. stimulate chemotaxis 5. stimulate INF- gamma to activate macrophages to come to area. 6. sntiobdy production of proteins expressed on opligodendrocytes 7. macrophages phagocytose oligodendrocytes eventually causes formation of plaqes (sclera) on axon, overtime becomes bultiple sclerosis
76
symptoms of MS
muscle weakness visual symptoms OPTIC NEURITIS (blurry double vision) unstable gait or balance pain/parathesias emotional cognitive disturbances fatigue sexual dysfunction speech swallowing abnormal sensations tingling, numbness sensitivity to heat bladder and bowel problems(frequency ,loss of control)
77
Dx of MS
alternative diagnosis considered and excluded atleast 2 documented clinical exacerbations seperated by time and space as well as 2 distinct mri lesions seperated by time and space dissemination in space (DIS) distinctly diff anatomical lesions on imaging in areas known to be affected by MS
78
clinically isolated syndrome
very first episode of neurologic symptoms lasting atleast 24hrs, caused by inflammation and demyelnination . pt may or may not go on to develop MS 1 exacerbatiom=n and 1 lesion while the clniician awaits a second exacerbartino AND LESION to make a dx of MS
79
clniically deifnite MS
2 attacks and clniical evidence of 2 sep lesions
80
labortatory definities MS
2 attacks, either para clinical or evidence of 1 lesion and CSF immunologic abnormalities or 1 attack, clinical evidence of 2 sep lesions and CSF abnormalities 1 attack or clniical evidence of 1 and paraclinical evidence of another seperate lesion, and CSF abnormalities
81
MRI findings indicitave of MS
4 or more white matter lesions >3,, 3 white matter ;esions , 1 periventricular lesions 6 mm diameter ir > ovoid lesions perpendicular to ventricles corpus collosum lesions open ring appearance
82
CSF spinal fluid studies strongly suggestive of MS
NORMAL RBC AND glucose normal or mildly elevated protein intrathecal igg synthesisw increased Igg index or 24 hr synthesis rate oligoclonal bands
83
Relapsing Remitting MS RRMS
most commmon (85% of pts) pts experience worsening of preexisting symptoms or onset of new symptoms fo rperiod >24hrs w.o concaminant fever, known as relapses, flare ups or exacerbations contrasted by symptom free periods, where the pts SS partially or completely dissappear
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Secondary Progressive MS (SPMS)
progressino of RRMS start out with clear cut relapses, turn into a steady progression approx 50% of pts prougressed to SPMS after 10-15 years with RRMS progression to spms was more common before advent of disease modifying meds
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primary progressive MS
realatively rare 10% steayd decline w.o clear cut relapses. med snmot generally effective at trwating this type
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Progressive Relapsing
most rare 5% steady disease progression, in addition ro clear cut periods of exacerbation
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general trt of MS
NOT a known cure trt aimed at controlling symptoms and maintaining function *disease modifying and treatment of relapses meds depending on symptoms pbhysicla therapy speech therapy planned exercise programs in early course of sidease
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treatment of acute exacerbation of MS
HIGH DOSE corticosteroids: reduce release of inflammatory markers 1.Methylprednisoloine (Solumedrol): w. or w.o taper a. h2/PPI for ulcer for ppx b. monitor for glucose watch for infection alternative: 2. corticotropin Acthar Gel: IM or SQ. for pts w. poor IV access
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Original ABCR Therapies Interferon beta MOA indication SE monitoring DDI Forms considerations:
Original ABCR Therapies MOA: specific interferon induced proteins and mechanisms by which interferon beta exeters its effects in MS not fully defines indication: relpasing forms such as CIS, RRMS, and SPMS SE: flu like symtpms!!!!! in up to 60% of pts. pts can premedicate with APAP or ibuprofen to decrease symptoms, fevers, chills, headahce chest pain, injection site reactions, depression, myalgia, arthtralgia , asthenia, malaise, diaphoresis, myasthenia, abdominal pain monitoring: MONITOR LFTS . can increase during therapy DDI forms: a. Avonex- interferon beta 1a *IM injection qweek titrated b.Rebif: subq injection given 3x a week titrated: interferon beta 1-a c. Plegridy SQ injection q2weeks a. Pegylated version BEtaseron, Exteavia (Interferon 1b) *subq in jection q other day considerations: all category C pts should have good injection site heigene monitor lfts. if pt has elevated lft, dont premedicate with APAp, use NSAID
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Original ABCR Therapies Glatiramer Acetate (Copaxone) MOA Form indication SE monitoring DDI considerations:
Original ABCR Therapies MOA: non fully knoen but could be related to alteration of t cell activation and differentiation forms: Capaxone, Glatopa subq inbjection once daily indication: relapsing forms inclusing CIS, RRMS, SPMS SE INJECTION SITE REACTIONS, transient flushing, vasodilation, chest tightness and or chest pain, asthenia, N&V, pain , arthtralgia, anxiety, palpitations, dyspnea,constriction of throat (pt can feel like they are almost have a a heart attack) monitoring DDI considerations: preg. category B
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Monoclonal AB in MS NAtalizumab (Tysabri) MOA Form indication SE monitoring DDI considerations:
MOA: prevents transmigration of leukocytes across the BB into inflames paranchmyal tissue Form: Tysabri IV infusion once q4weeks indication: relapsong forms including CIS, RRMS, and active SPSM SE: Progressive Multifocal Leukoencephalopathy (PML) fatal viral opportunistic infection. activates in immunocompromised pts. massive brian inflammation. it is demyelanting, causing impoairment of transmission of nerve impulses. myelin casnnot be regained once lost in PML *infusion reactions deprssion respiratory tract infection UTI depression headache fatigue cholelithiasis arthralgia monitoring : PML DDI considerations: preg category C prescribed through REMS program. infusion centers must be registered to monitor for the development of this condition
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three factors that increase ones risk for having PML (Progressive Multifocal Leukoencephalopathy)
testing positive for antibodies to JCV, prior use to certain immunosuppressant meds such as fingolimod and dimethyl fumurate, and using natalizumab for more than 2 years
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Monoclonal AB in MS Alemtuzamab (Lemtrada) MOA Form indication SE monitoring DDI considerations:
Monoclonal AB in MS MOA: targets cd52 on t and b lymphocytes, NK cells, MACROPHAGES AND MONOCYTES, CAUSING LONG-TERM REDUCTION OF CIRCULATING T CELLS. basically hitting the reset button on the immune system Form indication: RRMS, and SPMS, generally reserved for inadequate respononse to 2 or more medications SE: development of autoimmmune thyroid disorders such as graves disease rash in 90% headache pyrexia fatigue pruritis N&V chills insomnia chets dyscomfort dyspnea dyspepsia flushing uti, sinitis, uri, fungal infections monitoring :monitor tsh q3 mo until 48hrs after last infusion monitor cbc w. differential , Scr, and urinalysis w. urine cell counts at periodic intervals for 48 months after last dose moinitor for 2 hours after infucsion ECG prior to trt no live vaccines, wait 6 weeks after VZV annual hpv screen SS PML Baseline and annual skin exams DDI considerations: BBW: *can cause fatal autoimmune conditions such as immune thrombocytopenia and anti glomerular basement membrane disease must premedicate with corticosteroids 3 days before trt. *can also cause infusion rections. * can increase risk for malignancy administer antiviral ppx begiining on first day of trt trt. for 5 days and then a 3 day course at month 12 Preg. category C
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Monoclonal AB in MS Ocrelizumab MOA Form indication SE CI: monitoring DDI considerations:
Monoclonal AB in MS MOA: binds to CD20 on surface of b cells and depeletes tgem form circulation. b cels make AB and may play role in immune mediated damage to brain and spinal cord Form: IV . admin on day 1, then again 2 week slater, then subsequent doses admin. q6mo indication: PPMS (only one indicated for this) as well as relapsing forms such as CIS, RRMS, and active SPMS SE: infustion related reactions in up to 44% of pts, more common in higher dose and at first infusion, UTI, URI, headahce, nausea CI: hx of lifethreatening infusion reaciton to the mab, active HBV infection warning: hbv reactivation, screen for hbv herpes infection assess fo rinfection malignancies can occur more frequently monitoring DDI considerations: significantly recuces relapse rate, disability and disease activity on mri with RRMS AND SPMS
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ORATORIO Phase III trial
first large scale trial to show positive results of Ocrelizumab in PPMS
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Monoclonal AB in MS Ofatunamab (Kesimpta) MOA Form indication SE monitoring DDI considerations:
Monoclonal AB in MS MOA: binds to cd20 on b cells resulting in potent complement dependent cell lysis and ab-dependent cell mediated toxicity in cells that overexpress cd20 Form: SQ initially once weekly for 3 doses, maintenance once monthly start on week 4 indication can be taken @ home SE: infectoins, local site reacitons, headache warning:admin all live vaccines 2 weeks prior to theaspy monitoring : Serum quantitaive Immunoglobulins consult liver specialist DDI considerations: Store in fridge before amdin, allow to reach to room temp for about 15-30 min SQ initially once weekly for 3 doses, maintenance once monthly start on week 4 indication can be taken @ home
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Chemotherapy drugs in MS Mitoxantrone (novantrone) MOA Form indication SE monitoring DDI considerations:
Chemotherapy drugs in MS MOA: inhibits DNA repair through topoisomerase II. affects rapidly dividin cells secondary ewffects on immune system Form: IV Q3MO. indication: SPMS, PRS, or worsening RRMS . NOT FOR PPMS SE: cardio toxicity!!!, bone marrow suppresion, stomatitis, esophagitis , oral ulceration, nnv, alopecia, headache, fatigue, hepatic dysfuntion monitoring DDI considerations: category D lifetime dose of 100mg/m2 due to cardiotoxicity
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Chemotherapy drugs in MS Mavenclad (Clabridine) MOA Form indication SE monitoring DDI considerations:
Chemotherapy drugs in MS MOA: shut down of dna synthesis, leading to depletion of lymphocytes Form: 10 mg tabs. over 2 year course, w. 2 cycles /year indication: RRMS AND SOMS. NOT CIS SE: HA, Nnv, lymphoctyopenia, bone marrow depression, decreased AHGA monitoring : LFT CBC evaluate HIV, TB HBV, HVC, HZV, pregnancy test, MRI, SS acute infection DDI: substrate of BCRP/ABCG2, PGPABCB1, myeLOSUPRESSIVE AGENTS, echinacea, CI: in pts with current malignancy considerations: swallow whole do not chew cry hands for handleing sep form other meds for 3 hours no live vaccines graft vs host disease bone marrow supression cardiotoxicity BBW: ci in pts with current malignancy prior increased risk of pregnancy CI in pregnancy women and use effective contraception during trt and atleast 6 mop. after last dose. teratogenic
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Other oral drugs Fingolimod (Gilenya) MOA Form indication SE monitoring DDI considerations:
Other oral drugs MOA: acts on S1P receptors. depletes cd4+ and cd9 and t lymphocutes in the bloodstream, and inhibits release from lymphatic system Form: 0.5 mg QD indication: CIS, RRMS, and active SPMS in patients >10 y.o SE: HA, lymphopenia, URI, macular edema, increase in ABP, abdominal pain, diarrhea, dose dependent transient HRa reduction monitoring : need ECG prior to initiaiting, BP and HR taken. then checked qhr for 6hr. coontinue obserbing if bpm <45 or if hr is still at lowest after 6 hr. if it is, must continue monitoring baseline eye exam, can cause macular edema CI: MI, unstable angine, storke, TIA, decompensated HF, type IIor iii av block DDI considerations: Always requires 5 hrs first doe monitoring reduced lymph count by 70% heart rate decrease on day 1, attenuates over time mild increase in FE1 at high dose use contraception. teratogenic stoered at roomt emp
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Other oral drugs Mayzent / Siponimod MOA Form indication SE monitoring DDI considerations:
Other oral drugs MOA:S1P receptor modulator. decrease circulation lymphocytes and confines ot lymph system Form indication SE: HA, HTN, INcreased transaminases, bradycardia, etc. monitoring : cbc, lfts, ecg @ bedtime, VZV antibodied, BP, DDI: immunosupressants, qt prolonging agents, live vaccines warnings: macualr edema, bradycardia, AV block, qt prolongation. PRES ci:MI, unstable angine, storke, TIA, decompensated HF, type IIor iii av block considerations: unopened containers should be stored refrigerated. opened ok @ roop temp pts must undergo genetic testing: cyp2c9 genotype 1/1,1/2,2/2 titration w. maintenance 2 mg genotype 1/2,2/3: titration maintenance 1 mg cyp2c9 : ocntraindicated if therapy interupted, will need to retitrate first dose 6 hour monitroing for pts w. preexistingcardiac conditions including sinus bradycardia risk of rebound syndrome use ocntrraceptive . can cardiac harm fetus
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Other oral drugs Zeposia/ Ozonimod MOA Form indication SE monitoring DDI considerations:
Other oral drugs MOA: SP1 receptor modulator Form: indication SE monitoring : same as other sp1 modulators DDI: SSRI's, SNRI's, MAOIs , tyramine considerations: new drug on ma rket same as other sp1 receptor modulators MAO-I restrictions doesnt require first dose monitoring Tyramine warnings
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Teriflunomide Considerations
moa: blocks pyridine synthesis in rapidly dividing cells. produces cytostatic effect on t and b lymphocyte pperiphery, reduced b cell proliferation indicatin: relapsing forms delayed absoprtion w. food. but can be taken w. or w.o food se: HA, nasopharyngitis, alopecia, insomnia, etc. monitoiring: cbc 6 mo. b4 starting, LFT and billlirubin BBW: pregnancy category X. also decreases semen count in men
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Fumurate derivatives Dimethyl fumarate (Tecfidra)
apaptosis in acitvated t cells by inducing t helper 2-like cytokines AE: gi side effects!!!!! and flushing deleayed absorption, do not crush LFT monitor
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Fumurate derivatives Diroximel fumerate (Vulmerity) considerstions
causes less gi irritation than dimethyl fumerate BID dosing
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fumerate derivatives Monomethyl fumerate (Bafiertam ) considerations'
has less GI side effects than Dimethyl fumarate
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Symptomatic Trtment of MS Spasticity
abnormal increas ein muscle tone and stiffness baclofen dantrolene diazepine, clonazepam tizaidine gabapentin, tiagabine, pregabline botox dalfampridine
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Symptomatic Trtment of MS Bladder
80% of pts have OAB or urinary retention propantheline oxybutniin dicyclomine, bentyl DDAVP vatheritization imipramine prazosin botox solifenacin darifenacin trospium mirabegron
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Symptomatic Trtment of MS sensory (Parathesias, neuropsthic pain)
55% of ms pts have some clinical pain carbamezapine phenytoin TCA gabapentin lamotrigine pregablin duloxetine
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Symptomatic Trtment of MS fatigue, cognitive issues, emotional issues
amantadine SSRI/SNRI/ modafinil methylphenyldate destroamphetamine
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Symptomatic Trtment of MS pseudobulbar affect
occurs in ppl with ALS, AD, MS, PD, stroke TBI uncontrollable episodes of crying or laughing treatable w. Neudecta (Dextromethrophan and quinidine) moa unkown
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Symptomatic Trtment of MS walking
dalfampridine
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Cannabinoids in MS

TPX Neuro, Psych, & Sub abuse (7 decks)

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