Week 5: MS, Headache Flashcards
What is a Primary Headache disorders
Not due to/related to other medical condition
Primary Headache Disorders: Migraine
Epidemiology
women>men
~12% of the population
second most disabling
condition globally
Primary Headache Disorders
Migraine W.O aura Diagnostic criteria
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
Primary Headache Disorders
different phases of migraines
- 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
Primary Headache Disorders
Migraine patho
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
Primary Headache Disorders
Migraine triggers
stress
hormone changes/ menstruation
not eating
weather
sleep disturbance
perfume/ odor
neck pain
bright lights
alcohol
smoke
sleep late
heat
food
exercise
sexual ativity
Primary Headache Disorders
Migraine with aura diagnosis
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
Primary Headache Disorders
Migraine vs TIA
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
Primary Headache Disorders
General Migraine acute pharmacotherapy principles
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
Primary Headache Disorders
summary of acute migraine options for..
a)mild-mod. migraine attacks
b)mod.-severe migraine attacks
c)refractory mod-severe
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)
Primary Headache Disorders
General Considerations for NSAID use in Migraines
*acute treatment for mild-moderate migraines
*all nsaids are effective in migraine treatment
*can be combined w. triptans for more severe cases
Primary Headache Disorders
NSAIDs specifically indicated for migraines and considerations
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
Primary Headache Disorders
Bubalbital/APAP/Caffeine (Fioricet, Bac, Esgic, Zebutal) considerations
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)
Primary Headache Disorders
Butalbital/ASA/Caffeine considerations
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
Primary Headache Disorders
Triptans
indication:
mao:
AE:
caution:
CI
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.
Primary Headache Disorders
Triptans considerations
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
Primary Headache Disorders
Individual Triptan considerations
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
Primary Headache Disorders
Lasmiditan (REyvow)
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
Primary Headache Disorders
Lasmiditan considerations
can cause profound cns depression
must wait atleast 8 hrs between dosing and operating heavy machinery or driving
currently a brand name so expensive
Primary Headache Disorders
Rimegepant(Nurtec) considerations
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
Primary Headache Disorders
Ubrogepant (Ubrelvy) considerations
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
Primary Headache Disorders
anti-migraine ergot class considerations
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
Primary Headache Disorders
Ergotamine considerations
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
Primary Headache Disorders
Dihydroergotamine (DHE) considerations
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
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
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.
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
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
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
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
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
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
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.
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
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
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
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
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
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
nonpharm/ alternative migraine treatments
stress reduction techniques
dietatry changes
trigger avoidance
magneseium
vit. b2 (riboflavin
feverfew
butterbur
neuromodulation devices
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
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
Migraine Preventative therapies and considerations
Vit. b2 Riboflavin
migraine ppx
well tolerates
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
Migraine Preventative therapies and considerations
butterbur (Petasites)
migraine PPX
avois productz tht are not labeled as free from pyrrolizidine alkaloids (PA-free)
Dx of chronic migraine
migraines on >/= 15 days /months for > 3 mo.
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
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
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
migraine treatment for pts with cv or cerebrovascular diseases
gepants
lasmiditan
Acute migraine trtment for pregnant pt
first line: apap
avoid NSAIDS in 3rd semester
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
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
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
cluster headache etiology
prevalence <1%
male> female
onset 20-40 y.o
risk factors:
genetics
tobacco use
h/o head trauma
acute treatment of cluster headache
oxygen
sq (preferred)or intransal(alternative) sumatriptan
intransal zolmitriptan
preventative cluster headache treatment
verapamil (gold standard)
glucocorticoids
galcanezumab
lithium
topiramate
greater occipital nerve blocks
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
hemicrania continua trt
indomethacin gold standard
alternatives:onabotulinumtoxin A
occipital nerve stimulation
vagus nerve stimulation
peripheral nerve blocks
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
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
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
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
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
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
MEdication overuse headache
increased excitability of neurons in the cerbral cortex and trigeminal sysstem
vicious cycle of over use, more headaches, more medication
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
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
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
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
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
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)
MS
chronic autoimmune inflammatory disease that causes demyelantion of cns nerves
etiology of MS
ENVIRONMENTAL+GENETIC
Environmental
*EBV
*Human Herpes Virus-6
Genetic
*HLA DR-2 (mutation)
* XX female (20-40 yo)
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
- causes vasodilation in bbb
- increase capillary permeability between endothelial cells
- stimulate chemotaxis
- stimulate INF- gamma to activate macrophages to come to area.
- sntiobdy production of proteins expressed on opligodendrocytes
- macrophages phagocytose oligodendrocytes
eventually causes formation of plaqes (sclera) on axon, overtime becomes bultiple sclerosis
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)
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
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
clniically deifnite MS
2 attacks and clniical evidence of 2 sep lesions
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
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
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
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
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
primary progressive MS
realatively rare 10%
steayd decline w.o clear cut relapses.
med snmot generally effective at trwating this type
Progressive Relapsing
most rare 5%
steady disease progression, in addition ro clear cut periods of exacerbation
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
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
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
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
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
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
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
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
ORATORIO Phase III trial
first large scale trial to show positive results of Ocrelizumab in PPMS
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
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
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
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
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
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
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
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
Fumurate derivatives
Diroximel fumerate (Vulmerity) considerstions
causes less gi irritation than dimethyl fumerate
BID dosing
fumerate derivatives
Monomethyl fumerate (Bafiertam ) considerations’
has less GI side effects than Dimethyl fumarate
Symptomatic Trtment of MS
Spasticity
abnormal increas ein muscle tone and stiffness
baclofen
dantrolene
diazepine, clonazepam
tizaidine
gabapentin, tiagabine, pregabline
botox
dalfampridine
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
Symptomatic Trtment of MS
sensory (Parathesias, neuropsthic pain)
55% of ms pts have some clinical pain
carbamezapine
phenytoin
TCA
gabapentin
lamotrigine
pregablin
duloxetine
Symptomatic Trtment of MS
fatigue, cognitive issues, emotional issues
amantadine
SSRI/SNRI/ modafinil
methylphenyldate
destroamphetamine
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
Symptomatic Trtment of MS
walking
dalfampridine
Cannabinoids in MS
