Multiple Sclerosis

Multiple Sclerosis

 

Multiple sclerosis (MS) is a relapsing and often progressive autoimmune disorder of the white matter of the central nervous system.

Epidemiology

  • Incidence
    • 250,000 to 350,000 patients in the U.S. with MS
    • Highest prevalence in Northern Europe (30/100,000 persons)
  • Age – typically begins >20 years
  • Sex – F>M; 2:1

Risk Factors

  • Genetics
    • Most cases of MS are sporadic
    • 31% concordance rate among monozygotic twins
    • Presence of HLA-DR2 increases risk of MS

Pathophysiology

  • Immune-mediated disorder
  • Pathologic hallmark is the demyelinated plaque
  • Lesions have a predilection for optic nerves, periventricular white matter, brain stem, cerebellum, spinal cord white matter
  • Forms
    • Relapsing-remitting
    • Progressive
      • Primary
      • Secondary

Clinical Presentation

  • Early
    • Sensory disturbances
    • Unilateral optic neuritis – may be initial presentation
    • Diplopia (internuclear ophthalmoplegia)
    • Lhermitte sign (trunk and limb paresthesias evoked by neck flexion)
    • Limb weakness
    • Clumsiness
    • Ataxia, gait problems
    • Transverse myelitis
  • Late
    • Cortical signs – aphasia, apraxia, seizures
    • Extrapyramidal signs – chorea, rigidity
    • Cognitive impairment
    • Vertigo
    • Progressive quadriparesis and sensory loss
    • Spasticity

Diagnosis

  • Lumbar tap with fluid analysis
    • Oligoclonal bands present
    • Lymphocyte pleocytosis
    • Myelin basic protein
    • IgG index
  • MRI – presence of gadolinium enhancing lesions
  • Evoked potential testing (visual) positive

Differential Diagnosis

  • Metabolic disorders
    • B12 deficiency
    • Leukodystrophies
  • Autoimmune disorders
    • Sjögren syndrome
    • Systemic lupus erythematosus
    • Antiphospholipid syndrome
    • Chronic inflammatory demyelinating polyradiculopathy
  • Vascular disorders
    • Cavernous hemangioma
    • Central nervous system vasculitis
    • AV fistula
  • Neoplastic disorders
    • Spinal cord tumors
    • Paraneoplastic disorders
  • Infectious disorders
    • HIV myelopathy
    • HTLV-1 myelopathy
    • Lyme disease
    • Meningovascular syphilis

Treatment

  • Corticosteroids – high doses used most often in acute relapses
  • Interferons – beta 1-a, beta 1-b
  • Glatiramer acetate
  • Mitoxantrone
  • Possible adjunct therapies include methotrexate, plasma exchange, intravenous immune globulin

Prognosis

  • Largely unpredictable from individual to individual
  • 10% do well >20 years (so called benign MS)
  • 70% have secondary progression
  • Relapses are frequent in the first two years after disease is identified

See Also