Abstract
A scientific rationale for many of the therapies currently under trial in multiple sclerosis (MS) is provided by knowledge about the nature of the lesions and existing evidence (or reasonable inferences) concerning their pathogenesis. The MS lesion includes four important elements that lend themselves to therapeutic intervention: (1) inflammation, which involves vascular damage and edema, together with cellular infiltration that is primarily perivascular and mononuclear; (2) destruction of myelin and occasionally of other tissue components by infiltrating macrophages; (3) astrocytic proliferation and scarring after sufficient tissue damage; and (4) diminished conduction resulting from the edema, the demyelination, and the scar formation. Epidemiologic and genetic studies seem to have established firmly that MS occurs in persons with a genetic predisposition to the disease linked to genes both in the region of chromosome 6, which governs immune regulation, and in a region governing immunoglobulin formation, probably on chromosome 14. The disease is
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