Multiple paradigm shifts in multiple sclerosis.
OBJECTIVE
The present article reviews the currently ongoing scientific debate of our changing views on the pathogenesis of multiple sclerosis and the therapeutic strategies currently available for multiple sclerosis.


RESULTS
The most important observations include that (a) axonal loss accounts for permanent disability in multiple sclerosis, (b) remyelination should be possible in theory but fails for unknown reasons in the multiple sclerosis lesion, (c) inflammation can be beneficial, (d) treatment should be initiated early, and (e) immunosuppressive strategies exhibit beneficial effects in progressive forms of the disease.


CONCLUSIONS
Our current understanding of the immunopathogenesis of multiple sclerosis has changed in the past. Whereas demyelination was originally thought to be relevant for the lasting neurological deficit, it is nowadays commonly accepted that the extent of axonal loss dictates the degree of permanent clinical disability. How axonal damage can be prevented remains elusive. The interaction between the myelinating cell and the neuron gains increasing attention, however the evolving knowledge has not yet yielded new treatment concepts. Hence for the time being, it seems prudent to make optimal use of current approved therapies. Recent trials underlined the need for early initiation of treatment with immunomodulatory drugs. The superiority of one of the interferons is still a matter of debate, and a conclusive answer cannot be given at present. Finally, with mitoxantrone we have a drug at hand which can be used in progressive forms of multiple sclerosis, especially when other disease modifying drugs are not or no longer effective.
Kieseier
Bernd C
BC
Hartung
Hans-Peter
HP
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D016899:Interferon-beta / Q000627:therapeutic use; D008942:Mitoxantrone / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects
D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D008942:Mitoxantrone