Clinical implications of neuropathological findings in multiple sclerosis.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The pathological hallmarks of MS lesions in the brain and spinal cord are inflammation, demyelination, axon loss and gliosis. Recent studies revealed heterogeneity in the mechanisms leading to the formation of lesions, which include typical autoimmune patterns of demyelination involving T cells and macrophages, as well as antibody/complement as characteristic effector mechanisms. Additionally, oligodendrocyte dystrophy patterns of demyelination, with disturbances of oligodendroglial myelin protein expression and oligodendrocyte apoptosis, were observed. Treatment of MS has advanced dramatically in recent years, with the introduction of beta-interferons, glatiramer acetate and mitoxantrone. However, not all MS patients respond well to treatment with these drugs, and this may be a consequence of disease heterogeneity. Although immunomodulatory therapy has been clinically proven to be effective in patients with relapsing-remitting MS, studies in secondary-progressive MS patients have only demonstrated a positive therapeutic effect with interferon beta-1b. The pathology and pathogenesis of lesions suggest the need for a subtype-specific treatment, which may be possible when observations from pathology can be acted upon in the living MS patient. In addition to myelin and oligodendrocyte damage, the loss of axons represents another key element of MS lesions that lacks a therapeutic approach. However, axon-protective therapy is yet to be established and the mechanisms and effector molecules involved in axonal degeneration are still to be defined.
Brück
Wolfgang
W
Institute of Neuropathology, Georg-August University Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany. wbrueck@med.uni-goettingen.de
D015415:Biomarkers; D006801:Humans; D009103:Multiple Sclerosis / Q000145:classification* / Q000473:pathology* / Q000628:therapy*
D015415:Biomarkers