Summary: MS has typically been viewed as a disease with an autoimmune basis, which is thought to account for its association with other autoimmune diseases. The authors of this article challenge this conventional view of MS and propose that it is in fact a neurodegenerative disorder with relapses occurring as a consequence of immune reaction to the breakdown products from the degenerative process.

The authors term the conventional model of MS as an ‘outside-in’model and they hypothesise that in fact we should examine this disease as an ‘inside-out’ model. Firstly the inconsistencies in current clinical observations are outlined, including a review of pathology and therapeutics in MS. Secondly the differentphenotypes of MS are compared and it is argued that primary progressive MS represents the true disease, while the relapsing-remitting form is a secondary immune response to the underlying process. Comparisons are drawn with other neurological disorders and lastly a proposed mechanism is explored for this novel approach to this incurable disease.

This review article makes a compelling case for re-evaluating current thinking on the proposed mechanisms involved in the pathogenesis of MS.

Abstract
Multiple sclerosis (MS) is considered to be an autoimmune, inflammatory disease of the CNS. In most patients, the disease follows a relapsing-remitting course and is characterized by dynamic inflammatory demyelinating lesions in the CNS. Although on the surface MS may appear consistent with a primary autoimmune disease, questions have been raised as to whether inflammation and/or autoimmunity are really at the root of the disease, and it has been proposed that MS might in fact be a degenerative disorder. We argue that MS may be an'immunological convolution' between an underlying primary degenerative disorder and the host's aberrant immune response. To better understand this disease, we might need to consider non-inflammatory primary progressive MS as the 'real' MS, with inflammatory forms reflecting secondary, albeit very important, reactions.

Full article

Stys PK, Zamponi GW, van Minnen J, Geurts JJ.

Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

Source: Pubmed PMID: 22714021 & Nat Rev Neurosci. 2012 Jun 20;13(7):507-14. doi: 10.1038/nrn3275.(04/07/12)