MS Flashcards
Common PO therapies MS
Fingolimod,
Teriflunomide,
Dimethyl Fumuarate,
Cladribine
Clinical Features MS
– sensory, motor, cerebellar, cognitive
– optic neuritis
– internuclear ophthalmoplegia
– acute partial myelopathy
– partial/almost complete resolution of deficits with MS
– Lhermitte’s & Uhthoff’s symptoms
– Exercise induced symptoms
Smoking and MS
Increased relapse rate in smokers
Mimickers of MS
Neuromyelitis Optica Spectrum Disorder (NMOSD) - Separate disease
- NMO antibodies to aquaporin 4
Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD)
- separate disease
Classic MRI findings in MS
Characteristic sites
– periventricular, corpus callosum, centrum semiovale
– radiating out from corpus callosum = Dawson’s fingers
– brainstem, cerebellum
Test in MS
- Magnetic Resonance Imaging
- Evoked Potentials (EPs) - good to find lesions you can’t see clinically or on MRI
– VEP = visual EP (optic neuritis – subclinical disease)
– SEP = somatosensory (limbs)
– BAER = brainstem EP = auditory pathways. - Central Motor Conduction Time (CMCT)
– motor pathways = corticospinal tracts to limbs
– MEPs = Motor Evoked Potentials - Lumbar puncture - CSF
– basic CSF studies normal, maybe a few lymphocytes.
Oligoclonal bands +ve in CSF but NOT in serum, Increased CSF IgG synthesis.
Other Ddx for MS
– NMOSD & MOGAD
– Inflammatory diseases
* SLE, Sjogren’s, PAN, Behcet’s, ADEM etc
– Infectious diseases
* HIV, HTLV 1, PML, Lyme disease, Syphilis
– Granulomatous disease
* Sarcoidosis, Wegener’s granulomatosis
– Diseases of Myelin
* Adrenoleukodystrophy, Metachromatic Leucodystrophy
– Miscellaneous
* Spinocerebellar ataxia, vitamin B12 deficiency, ACM, mitochondrial cytopathy, vascular disease, CADASIL, Susac’s syndrome etc etc
Pregnancy and MS
– Relapse rate reduced during pregnancy, especially in 3rd trimester.
– Increase in relapse rate in 6 months after delivery
– No increase in sustained neurological disability due to pregnancy
– No increase in
* stillbirths, ectopic pregnancy, etc
- Discontinuation of DMTS before attempting a planned pregnancy is usually recommended
- Caution in using Gonadotropin-releasing hormone (GnRH) protocols for IVF in women with MS as this may significantly increase the MS relapse rate
MS Poorer Prognostic Factors
- Demographics
– Male
– Older than 40 years at onset of disease - Relapse Characteristics
– Frequent relapses early in disease course
– Multifocal relapses
– More severe relapses
– Shorter inter-attack interval
– Poorer recovery from relapses - Disease Course
– Rapid accrual of disability
– Progressive rather than relapsing remitting course from onset - MRI Features at onset predicting poorer prognosis
– High T2 lesion load
– >2 GAD enhancing lesions
– >T1 hypointense lesions (“Black Holes”)
– Early atrophy
– Infratentorial as opposed to supratentorial lesions - MRI Features during Treatment predicting poorer prognosis
– New T2 lesions
– >1 GAD enhancing lesion
MS treatment acute exacerbations
PO/ IV steroids
Natalizumab brand/ MOA
Tysabri (alpha 4 integrin antagonist)
monoclonals in MS
Alemtuzumab, Rituximab, Ocrelizumab
Sx of PML
Progressive multifocal leucoencephalopathy
- Rapidly progressive demyelination in brain
- Dementia, motor dysfunction, visual loss
- Previously mortality 30-50% in 3 months if untreated & late Dx
Patients who get PML
immunocompromised
- AIDS,
- transplant Pt,
- Immune system altering drugs eg , MS Pt on DMTs
Alemtuzumab MOA
Humanised monoclonal Ab binds CD52 (on B cells)
AE Alemtuzumab
– 2-3% ITP ( may be fatal)
– 20-30 % autoimmune thyroid disease at 5 years
– DON’T give live vaccines after Alemtuzumab Rx
– Listeria meningitis & cryptosporidial infections (rarely)
– Immune mediated conditions including hepatitis and haemophagocytic lymphohistiocytosis, bleeding in lungs, MI, stroke, arterial dissection and severe neutropaenia
Ocrelizumab MOA
Humanized anti CD20 monoclonal antibody
- Depletes B lymphocytes
Fingolimod MOA
- Decreases ability of lymphocytes to enter CNS by preventing the egress of lymphocytes from lymphatic tissues.
Fingolimod AE
- Potential serious cardiac side effects.
- 1 st dose monitoring for bradycardia. Heart block.
- OCT monitoring for macula edema (?1% Pts)
- Need to have antibodies or to immunise patients against Varicella Zoster before Rx
- > 15 PML cases reported so far
Teriflunomide MOA
Inhibits pyrimidine synthesis (dihydroorotate dehydrogenase inhibitor)
AE Teriflunamide
- Hypertension
- LFT & FBS abnormal
- Alopecia, diarrhea
– X categorisation regarding pregnancy
– Prolonged half-life due to enterohepatic circulation
– Cholestyramine or activated charcoal can hasten elimination
Dimethyl Fumarate MOA
Mechanism of action in MS is unclear.
Dimethyl Fumarate AE
– Flushing -30%
– Self limited GI side effects -30%
- Lymphocytes decrease by = 20-30% (possibly more)
– Monitoring required
– Discontinue if lymphocytes <0.5 for 6 months
Pathophys NMO Disorder
Astrocytopathy – Aquaporin 4 Abs in high concentrations in foot processes of astrocytes along endothelial lining of blood brain barrier
Pathology is ?? complement mediated destruction of astrocytes with secondary demyelination
demographics NMO Disorder
90% patients are women.
Disproportionately affects non-Caucasians.
NMOD clinically vs MS and with Ix
- Optic Nerve disease important (often more severe than ON in MS)
- Spinal Cord disease important (often more severe than myelitis in MS)
- May be significant pleocytosis on CSF. Usually no OCBs (maybe transientlypresent during a relapse).
Doesn’t respond to interferon or other MS treatments
NO decrease in chance of relapse during pregnancy (cf MS)
NMOSD has a worse prognosis than MS
– 50% walking problems at 5 years
MOGAD
Myelin Oligodendrocyte Glycoprotein Associated Disease
– MS mimicker (screen ?MS patients for this & for NMOSD).
– Important to differentiate from RRMS
– ADEM presentation in children
– Opticospinal (NMO type) presentation in adolescents & adults
– Maybe monophasic or recurrent disease course
Pathophys MOGAD
– Oligodendrocyte directed pathology = Oligodendrocytopathy
MS and vaccinations
Basic INO presentation
– complex eye movement disorder
* loss or slowed aDduction
* horizontal nystagmus of aBducting eye
* lesion in MLF on side of decreased Adduction
* if bilateral is usually coupled with vertical nystagmus on upward gaze.
– maybe bilateral or unilateral
