MS tx Flashcards
Multiple sclerosis
Diagnostic criteria of MS
-dissmination in Time and space
-REQUIRES at least 2 demyelination-related episodes separated by time and space
-use MRI and CSF testing
dissemination in Time (DIT)
-time between evidence of new lesions in subsequent MRIs (30 days)
-damage that has happened more than once
Dissemination in Space (DIS)
-need for >1T2 lesion appearing in at least 2 of 4 MS-typical CNS regions:
-corticol, periventricular, infratenorial, spinal cord
-damage that is in more than one place
Types of MS
-clinically isolated Syndrome (CIS)
-Relapsing Remitting (RRMS)
-Secondary Progressive (SPSM)
-Primary Progressive (PPMS)
-Progressive Relapsing (PRMS)
Clinically isolated syndrome (CIS)
-first demyelinating event involving:
-optic nerve
-cerebrum
-cerebellum
-brainstem
-spinal cord
-most will develop MS in 20 years
Relapsing Remitting MS (RRMS)
-85%
-relapses w complete or partial remission between
-most become progressive over time
-white 30 year old women
Secondary Progressive MS (SPMS)
-80% of RRMS
-fewer relapses
-continuing disability
Primary Progressive MS (PPMS)
-10-15%
-progressive from onset
-minor improvements or periods of stability
-more common in pt dx in later years >50yo
Progressive Relapsing MS (PRMS)
-least common
-5%
-steadily worsening
-later, clear, acute relapses
-may be some recovery but no remission between relapses
Disease modifying drug therapy is focused on:
-RRMS type of MS
-one exception for PPMS
-based on current drug target of inflammation vs neurodegeneration
Expanded Disability Status Scale (EDSS)
-assess severity of MS
-0-10
-10 is death, 5 is cane
-mostly based on ability to get around
-pt presenting w RRMS progresses to 4 within 7 years of dx
-score of 4: able to walk w/o aid or rest but has severe disability (one big disability or a bunch of small disabilities
Goals of MS tx
-start early, reduce relapses to stall neurodegeneration
-tx acute relapses for better remission
-begin DMDs at CIS stage if possible (target inflammation)
-improve QOL: fatigue, gait, pain
Treatment of acute attacks
- high-dose corticosteroid
-most pt will be inpatient (IV)
-methylprednisolone, ACTH, prednisone
Methylprednisolone
-500-1000mg IV qd for 3-7 days
-w or w/o: oral taper over 1-3 weeks
-GIVE TO PT W OPTIC NEURITIS
ACTH
-or plasma exchange
-$$$
Prednisone
-if outpatient
-oral 1250mg qod x 5 doses
-no need to taper
Oral MS meds
-Cladribine (Mavenclad)
-fumarates
-ginolimod
-ozanimod
-ponesimod
-siponimod
-teriflunomide
Injectable MS meds
-IFN-B1a/b*
-PegIFN-B1a*
-Glatiramer acetate*
-Ofatumumab (Kesimpta)
Infusion MS meds
-Alemtuzumab*
-Mitoxantrone
-Natalizumab*
-Ocrelizumab*
-Ublituximab-xiiy
Progressive Multifocal Leukoencephalopathy
-rare side effect caused by reactivation of dormant JCV
-cause myelin producing cells to break down
-looks similar to MS relapse
-50-80% of abults have JCV aBs and are at risk
-50% mortality
-pt MUST BE TESTED FOR JCV ANTIBODIES
MS Vaccines
-inactivated vax preferred
-live not recommended bc weakened immune response
-alemtuzumab - no live vax
-varicella vax in pt w no chx pox especially if starting an immunosuppressant (fingolimod, almetuzumab)
dimethyl, diroximel, monomethyl fumarate
-capsule should NOT be opened/chewed/crushed
-monitor LFTs and CBC (neutropenia
-associated w PML
-can cause flushing = take aspirin 30 min before dose
Sphingosine 1-phosphate receptor modulator drugs
-fingolimod
-ozanimod
-ponesimod
-sponimod
S1P drugs (-imods)
-AVOID in past arrhythmia dx or MI, unstable angina, stroke/TIA, class III-IV HF in past 6 months
-monitor 6h after 1st dose (bradycardia – ECG)
-monitor CBC (inc risk of infection
-routine eye exam (macular edema)
-d/c can worsen MS sx
S1P special notes
-CYP2C9 testing required before going on siponimod
Glatiramer acetate
-injection side effects
-flushing, sweating, dyspnea, chest pain, anxiety, itchin
-lipotrophy – rotate inj sites
-chest pain (not significant)
-maybe preferred in pregnancy
Interferons
-SQ or IM qod to q2 weeks depending on dosage
-flu-like sx after injection, pretx w analgesic, dose at bedtime and titrate gradually
-depression, suicidal thoughts
-elevated LFTs and TSH
Monoclonal Antibodies
-Alemtuzumab
-Natalizumab
-Ocrelizumab
-complete vax at least 6 weeks before tx
-can premed w steroid, antihistamine, acetaminophen prior to dose
Alemtuzumab
-REMS program
-possible fatal infusion rx and autoimmune conditions
-inc risk of malignancies
-AVOID in HIV infection (dec CD4 count)
Natalizumab
-REMS program
-inc PML risk
Ocrelizumab
-PPMS, CIS, RRMS, SPMS
-AVOID in hep B
-inc risk of malignancies
MS tx in pregnancy/contraception
-AVOID teriflunomide
-Mitoxantrone (oc + test qdose)
-Fingolimod (oc during + 2 months after tx)
-Ozanimod (oc during + 3 months after dc)
-Ponesimod (oc during + 7 days after dc)
-Siponimod (during + 10 days)
-Ocrelizumab (during + 6 months)
-Cladribine (oc + barrier + 6 months NO BREASTFEEDING)
MS and pregnancy
-rates of relapse decrease
-inc for the first 3 months postpartum, then back to normal rate
-dc MS therapy prior to conception
-DO NOT breastfeed on MS tx
Pseudobulbar affect
-freq and inappropriate episodes of crying, laughing, or both unrelated to actual mood
-unknown cause (serotonin, dopamine, glutamate disrupted from brainstem to cerebellum)
-Neudexta (dextromethorphan/quinidine) for tx
Neudexta (dextromethorphan/quinidine)
-tx pseudobulbar affect
-dextromethorphan:
-agonist at sigma-1 receptors
-supress excitatory NT release
-antagonist at NMDA receptors
-P450 substrate (metabolized to dextrorphan in periphery = cant cross BBB)
-quinidine:
-P450 2D6 inhibitor = block conversion of dextromethorphan = can cross BBB
Gait abnormalities and walking speed
-physical therapy/gait training/exercise
-Dalfampridine
Dalfampridine (Ampyra)
-gait tx
-blocks K channels
=prevents repolarization
=prolong action potential and transmission
-may improve walking speed
Dalfampridine (Ampyra) side effects
-ER (preferred): UTI, insomnia, dizziness, headache, nausea
-IR: seizures (AVOID in pt w seizures)
Symptomatic management
-see table
-bowel/bladder dysfunction
-sexual dysfunction
-psychiatric probs
-beaware of other drugs making this worse (anticholinergics making bladder worse)
-baclofen for spasticity
Medical marijuana in MS
-OCE/THC dec pt reported scores but not objective scores (spasticity)
-OCE effective against central pain
-THC maybe effective to dec painful spasms
-both likely ineffective for tremor and bladder
markers of tx failure
-no dec in relapse rates
-aquired disabilities
-MRI activity
-continued freq relapses justify alt tx or mitoxantrone or chemo
