Multiple Sclerosis

Snapshot

  • A 32-year-old women presents to her physician complaining of double vision. This has been very distressing for her. She has a past medical history significant for type 1 diabetes, treated with a continuous subcutaneous insulin pump. Upon further questioning, she mentions she experienced arm weakness and numbness that resolved spontaneously over the course of a couple weeks. Physical examination is notable for impaired adduction of the right eye, and nystagmus on abduction of the left eye on left lateral gaze.

Introduction

image 187
  • Autoimmune inflammation/demyelination of CNS neurons
    • destruction of oligodendrocytes mediated by CD8 T-cells and Th1/Th17 helper T cells  
    • specific anti-MBP (myelin basic protein) antibodies
      • can find ↑ protein (IgG) in CSF
    • over time white matter plaques accumulate in the brain and the spinal cord
  • Epidemiology
    • gender bias
      • ↑ in women
    • race bias
      • ↑ in whites
    • onset commonly between 20-40 years
    • ↑ in temperate climates
  • associated with HLA-DR2

Presentation

  • Symptoms – may have multiple neurologic symptoms separated in time and space
    • motor involvement
      • hemiparesis
      • MLF syndrome → internuclear ophthalmoplegia
        • nystagmus
      • scanning speech (sound intoxicated)
      • intention tremor
    • sensory involvement
      • hemisensory symptoms
      • heat sensitivity (“Uhthoff phenomenon”) 
        • a temporary worsening of symptoms when exposed to increases in temperature
      • optic neuritis
        • sudden loss of vision
        • afferent pupilary defect (Marcus Gunn pupil) 
    • autonomic involvement
  • bladder/bowel incontinence

Evaluation

  • LP
    • ↑ leukocytes
    • ↑ γ-globulins
      • results in oligoclonal banding
    • ↑ MBP
    • normal glucose
  • Imaging
    • must include two demyelinating lesions separated in time and space
    • MRI is gold standard
      • hyperintense on T2 and FLAIR with enhancement of acute lesions
      • demyelinating periventricular plaques known as Dawson’s fingers
  • may have preservation (early) or destruction (late) of axons within plaques

Differential

  • Acute disseminated encephalomyelitis
  • Neuromyelitis optica (NMO)
  • Idiopathic transverse myelitis

Treatment

  • Medical
    • β-interferon
    • high-dose steroids (dexamethasone)
      • speed recovery of ocular symptoms but do not change overall progression of disease
    • glatiramer
    • natalizumab https://step1.medbullets.com/images/question_step_1.png
      • ↑ risk of progressive multifocal leukoencephalopathy
    • rituximab
      • ↑ risk of progressive multifocal leukoencephalopathy
  • Symptomatic treatment for neurogenic bladder, spasticity, and pain

Prognosis, Prevention, and Complications

  • Can exhibit multiple patterns of disability progression
    • primary progressive – steady decline in function over time
    • relapsing remitting – periods of relative stability alternating with declines
    • secondary progressive – relatively stable at first followed by steady decline