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  • Degradation of myelin sheath surrounding axons in CNS
  • Inflammatory process mediated by T & B ymphocytes, antibodies, macrophages, & complement (N Engl J Med 2006;354:942)
    • Activated peripheral T cells activate matrix metalloproteinases → disrupt BBB → entry to CNS
    • Cytokines released in CNS cause upregulation of immune response → damage to myelin sheath
    • Cytokines primarily involved in the inflammatory process include tumor necrosis factor-α, interferon-γ, & interleukins-1, -2, -12, -17, & -23 (Ann Neurol 1994;36:S6)
  • Demyelination leaves neurons vulnerable to damage; if neurons severed → irreversible; appears on T1-weighted MRI as a hypointense lesion or “black hole” (N Engl J Med 1998;338:278)

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  • Diagnosis of exclusion; based on clinical symptoms & MRI results (Ann Neurol 2001;50:121)
    • Demonstration of “lesions separated in space & time”; at least 2 episodes of neurological damage at distinct sites within CNS that cannot be caused by another mechanism
    • A diagnosis of clinically definite multiple sclerosis (CDMS) can also be made on a single MRI along with a clinical history suggestive of MS
    • Periventricular lesions characteristic of MS (“multiple sclerosis” is derived from multiple sclerosed plaques in CNS): total volume of T2-weighted lesions may correlate with development of disability; gadolinium-enhancing lesions indicate disruption of the BBB & a new active lesion (Neurology 2003;61:1332)
    • Brain atrophy may also correlate with development of disability (Neurology 2002;59:1412)
    • White & gray matter involvement in the CNS
  • CSF evaluations helpful if MRI not conclusive (IgG ↑ in CSF, normal in serum; oligoclonal bands may be present) (Ann Neurol 1994;36:S100)
  • Visual evoked potentials may be used only to aid a formal diagnosis (Ann Neurol 2005;58:840)

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Clinical Course of Disease

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  • Clinically isolated syndrome (CIS): 1st MS-related event (no prior dx of CDMS)
    • First clinical symptom varies drastically from pt-to-pt, but often includes visual disturbances (including optic neuritis), other sensory disturbances, or motor dysfunction
  • Radiologically isolated syndrome (RIS): MRI showing lesions consistent with a diagnosis of MS in the absence of any MS-like clinical symptoms (MRI ordered for an unrelated reason such as migraine or trauma)
  • Clinically definite MS: classified into 4 categories (Ann Neurol 1994;36:S6)
    • Relapsing-remitting MS (RRMS): 85% at diagnosis
      • Relapse: new symptoms lasting at least 24h & separated from other attacks by at least 30d; typically correlated with new MRI lesions
      • Remission: dissipation of relapse symptoms; may or may not return to baseline level of disability
    • Secondary-progressive MS (SPMS): RRMS eventually progresses to SPMS
      • Relapses & remissions become difficult to distinguish; disability accumulates more quickly than in RRMS (new MRI lesions less common)
    • Primary-progressive MS (PPMS): do not have relapses & remissions, disability ↑ progressively over time; disease-modifying drugs are significantly less effective
    • Progressive-relapsing MS (PRMS): experiences relapses & remissions, but disability accumulates between relapses (rarest form, typically treated same as RRMS)
  • Benign MS: retrospective diagnosis, minimal relapses, & disability

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Treatment of Acute Exacerbations

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  • Treatment goals: restoration of baseline functioning (if exacerbation caused functional decline); if no ...

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