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Pathogenesis

Trapp BD, Stys PK.

Cleveland Clinic Foundation, Cleveland, OH, USA.

 Lancet Neurol 2009;8:280–91.

Editor’s note: In the past decade, multiple sclerosis (MS) has been increasingly recognized as both a demyelinating and neurodegenerative disease. This review recapitulates broadly accepted evidence for axonal damage in MS and its relevance for the secondary chronic progressive disease phase. The authors summarize the concept of demyelination representing a state of chronic “virtual hypoxia” for the denuded axon, causing increased calcium influx and ultimately degeneration. Finally, the review conclusively deduces how sodium channel blockers, glutamate receptor antagonists, and calpain inhibitors may extend therapeutic options in MS in the future.

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