Multiple Sclerosis

Multiple sclerosis (MS) is a chronic immune mediated demyelinating and neurodegenerative disease of the central nervous system.

• Prevalence is about 30 to 300 per 100,000, with onset at 20 to 40 years and a female to male ratio of about 3:1.

• Risk factors: Epstein-Barr virus infection, low vitamin D, smoking, obesity in adolescence, HLA-DRB1*15:01, northern latitude.

• Courses: relapsing remitting (85% at onset), secondary progressive, primary progressive (10 to 15%). Clinically isolated syndrome and radiologically isolated syndrome precede some cases.

• Pathology: perivenular inflammatory plaques with demyelination, axonal loss and cortical atrophy.

• Complications: disability accumulation, bladder and bowel dysfunction, spasticity, fatigue, depression, cognitive impairment.

• Optic neuritis (painful monocular visual loss, afferent pupillary defect), internuclear ophthalmoplegia, diplopia, vertigo.

• Partial transverse myelitis: sensory level, limb weakness, Lhermitte sign, bladder urgency.

• Uhthoff phenomenon (worsening with heat), trigeminal neuralgia in a young adult, cerebellar ataxia.

• Red flags for alternatives: progressive course in young patients, early dementia, peripheral neuropathy, systemic features.

• 2017 McDonald criteria: dissemination in space (two or more of periventricular, cortical or juxtacortical, infratentorial, spinal cord lesions) and in time (new lesion or simultaneous enhancing and non enhancing lesions, or CSF oligoclonal bands).

• MRI brain and whole spine with gadolinium; central vein sign and paramagnetic rim lesions support the diagnosis.

• CSF: oligoclonal IgG bands (95%), raised IgG index. Visual evoked potentials if needed.

• Exclude NMOSD (AQP4), MOGAD, vitamin B12 deficiency, sarcoidosis, lupus, Lyme disease, small vessel disease, HIV.

• Baseline JC virus serology, hepatitis B, varicella zoster serostatus and lymphocyte count before therapy.

Acute relapse

• Methylprednisolone 1 g IV daily for 3 to 5 days (or oral 1250 mg daily for 3 days). Plasma exchange (5 to 7 exchanges) for steroid failure.

Disease modifying therapy (high efficacy early in active disease)

• Anti CD20: ocrelizumab 600 mg IV every 6 months, ofatumumab 20 mg SC monthly, ublituximab, rituximab.

• Natalizumab 300 mg IV every 4 weeks (extended interval every 6 weeks if JCV index low), alemtuzumab 12 mg IV daily for 5 days then 3 days at 12 months.

• Cladribine 3.5 mg/kg over 2 years, fingolimod 0.5 mg daily, siponimod 2 mg daily (secondary progressive), ozanimod, ponesimod.

• Moderate efficacy: dimethyl fumarate 240 mg twice daily, teriflunomide 14 mg daily, interferon beta 1a 30 micrograms IM weekly or 44 micrograms SC three times weekly, glatiramer acetate 20 mg daily or 40 mg three times weekly.

• Ocrelizumab for primary progressive disease. Autologous stem cell transplant for aggressive refractory cases.

Symptomatic

• Spasticity: baclofen 5 to 20 mg three times daily, tizanidine, botulinum toxin. Fatigue: amantadine 100 mg twice daily, modafinil. Walking: dalfampridine 10 mg twice daily.

• Bladder: oxybutynin, mirabegron, intermittent self catheterisation. Neuropathic pain: gabapentin, duloxetine.

• Vitamin D 2000 IU daily, exercise, smoking cessation, vaccination (avoid live vaccines on immunosuppression).

• Pregnancy: stop teriflunomide, fingolimod and cladribine before conception. Natalizumab or ofatumumab may continue in selected high risk cases.

• MRI annually and clinical review every 6 months.