Multiple Sclerosis

An autoimmune demyelinating disorder with CNS lesions separated in time and space.” “Demyelination affects grey and white matter of the brain, spinal cord and optic nerves. Disease courses: relapsing–remitting (most common), secondary progressive, primary progressive, and progressive-relapsing.

Demographics

• Females ~3× males, typically 20–40 years
• ~80% relapsing–remitting at onset; ~20% follow a more benign course

Clinical features

Transient motor or sensory disturbances that resolve then recur in a different location, typically evolving over days. Initial presentations are monosymptomatic ~80% of the time.

• Visual disturbance — blurred vision, loss of vision in one eye (confirm it is not a homonymous hemianopia → think stroke), diplopia
• Weakness in one or both legs
• Sensory impairment of lower limbs/trunk — paraesthesia, clumsiness, band-like truncal sensations
• Vertigo

Examination — upper motor neuron signs: optic atrophy, weakness, hyperreflexia, extensor plantar responses, nystagmus, ataxia, incoordination, impaired sensation.

Investigations

• MRI — contrast-enhancing lesions or new T2 lesions
• LP — CSF oligoclonal bands (may be absent in ~10% even with active disease)
• Visual evoked potentials — abnormal in ~90%

Diagnosis — McDonald 2017 criteria

Diagnosis requires demonstration of dissemination in space and in time; CSF-specific oligoclonal bands can substitute for dissemination in time in a clinically isolated syndrome. In practice, diagnosis usually follows a second relapse with new lesions in a different location on MRI. Refer everyone to neurology for diagnosis and management.

Dissemination in space — ≥1 T2 lesion in ≥2 of four characteristic locations: periventricular, cortical/juxtacortical, infratentorial, spinal cord. (Optic nerve lesions cannot be used to fulfil the 2017 criteria.)

Dissemination in time — either a new T2/gadolinium-enhancing lesion versus a prior baseline scan, or simultaneous enhancing and non-enhancing T2 lesions on a single scan.

Primary progressive MS — ≥1 year of disability progression plus two of: ≥1 characteristic brain T2 lesion; ≥2 spinal cord T2 lesions; CSF-specific oligoclonal bands.

Course

Difficult to predict. Earlier onset (<30 yrs) tends toward more benign disease; later onset (>50 yrs) toward a more aggressive course. The likelihood of developing MS after a single episode of optic neuritis is ~60%.

Treatment

• Mild symptoms (numbness/tingling) — confirmation, rest and reassurance
• Moderate relapse — prednisolone
• Severe relapse — hospital: IV methylprednisolone ± plasma exchange
• Spasticity — baclofen (5 mg TDS, titrating over a week to 10–25 mg TDS; review at 6–8 weeks; taper over 2 weeks if stopping); a benzodiazepine (clonazepam 0.5 mg nocte, up to 2 mg) for night spasms
• Fatigue — usually multifactorial; investigate other causes; amantadine or modafinil sometimes used on expert advice

Disease-modifying therapy (relapsing forms) — the landscape has expanded substantially beyond older agents (interferon beta, glatiramer acetate, natalizumab, alemtuzumab): oral agents (fingolimod, dimethyl fumarate, teriflunomide, siponimod, cladribine) and anti-CD20 monoclonal antibodies (ocrelizumab, ofatumumab) are now commonly used, with anti-CD20 therapy often positioned as high-efficacy first-line treatment — about half of Australians treated for relapsing MS are now on an anti-CD20 agent.