Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content ++ Degradation of myelin sheath surrounding axons in CNSInflammatory 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 CNSCytokines released in CNS cause upregulation of immune response → damage to myelin sheathCytokines 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) ++ 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 mechanismA diagnosis of clinically definite multiple sclerosis (CDMS) can also be made on a single MRI along with a clinical history suggestive of MSPeriventricular 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 CNSCSF 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) +++ Clinical Course of Disease ++ 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 dysfunctionRadiologically 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 lesionsRemission: dissipation of relapse symptoms; may or may not return to baseline level of disabilitySecondary-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 effectiveProgressive-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 +++ Treatment of Acute Exacerbations ++ Treatment goals: restoration of baseline functioning (if exacerbation caused functional decline); ... Your MyAccess profile is currently affiliated with '[InstitutionA]' and is in the process of switching affiliations to '[InstitutionB]'. Please click ‘Continue’ to continue the affiliation switch, otherwise click ‘Cancel’ to cancel signing in. Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth