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Multiple Sclerosis


Multiple Sclerosis

Definition

  • Autoimmune, chronic inflammatory, demyelinating disease of the central nervous system; intermittent episodic neurologic impairments of varying severity caused by multiple demyelinating lesions, often of different ages

  • Key pathologic features:

    • Perivenular inflammation with primary myelin loss and relative sparring of axons—early in disease

    • Significant axonal destruction as disease progresses

    • Demyelination and axonal injury confined to CNS

    • Subtypes include relapsing-remitting, primary progressive, secondary progressive, and progressive relapsing types

Clinical Features

Epidemiology

  • About 10,000 new cases per year in the United States; prevalence 10 to 100 per 100,000 individuals depending on region

  • Affects all ages, most commonly found in individuals 18 to 50 years old

  • Overall female predominance (2 : 1 female-to-male ratio)

  • Incidence increases in northern latitudes

  • Risk factors: exposure to Epstein-Barr virus, vitamin D deficiency, smoking

Presentation

  • Highly variable

    • Relapsing-remitting type (85% of cases): sporadic attacks last 2 to 10 days followed by improvement over several months

    • Primary progressive type (15% of cases): clinical course is progressive without remissions or relapses

    • Secondary progressive type: conversion of relapsing/remitting to progressive disease

    • Optic neuritis may be first manifestation of disease

  • Exacerbations of multiple sclerosis (MS) characterized by symptoms that reflect CNS involvement including muscle weakness, sensory change, movement difficulties, bowel/bladder dysfunction, ataxia, and visual impairments (optic neuritis); cognitive and psychiatric symptoms can also occur

  • Symptoms occur as episodic attacks at different time intervals usually affecting different locations within the brain or spinal cord

  • Oligoclonal bands found in CSF of ≥90% patients with clinically definitive MS

Prognosis and Treatment

  • Symptoms usually relapsing and remitting; 50% of patients will have progressive disease with few relapses and gradual deterioration of neurologic function

  • 5% of patients will have rapidly progressive deterioration

  • Average of 30 years from disease onset until death

  • Corticosteroids for acute relapses; may use plasmapheresis

  • Immunomodulatory medications: interferon beta-1a and beta-1b, glatiramer acetate, mitoxantrone, natalizumab

  • Adverse effect of natalizumab therapy for multiple sclerosis: progressive multifocal leukoencephalopathy (PML)

    • PML occurs in about 0.2% of patients

    • Increased risk with positive anti-JC virus antibodies, prior immunosuppressant therapy, increased duration of natalizumab therapy

Imaging Characteristics

  • MRI: ovoid T2-hyperintense white matter lesions (“plaques”), particularly in periventricular regions; may have associated edema in acute cases

  • 1-hypointense lesions (“holes”) may represent chronic tissue axonal damage or more severe injury

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