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Will the real multiple sclerosis please stand up?

An Erratum to this article was published on 04 July 2012

This article has been updated

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.

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Figure 1: Schematic contrasting the two competing hypothetical aetiologies of multiple sclerosis.
Figure 2: Multiple sclerosis as an immunological convolution.

Change history

  • 04 July 2012

    On page 508 of this article, "alemtuzumab (a monoclonal antibody directed against CD25 (also known as interleukin-2 receptor subunit-α is expressed on leukocytes)" should have read "alemtuzumab (a monoclonal antibody directed against CD52, which is expressed on lymphocytes)" This has been corrected in the online version.

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Acknowledgements

The authors thank C. Polman for critical reading of the manuscript. Work in the authors' laboratories is supported by the MS Society of Canada, Canadian Institutes of Health Research, Alberta Innovates — Health Solutions, Canada Research Chairs and the Dutch MS Research Foundation.

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Glossary

Demyelinating myelopathy

Pathology of the spinal cord mainly due to loss of myelin from afferent and efferent spinal axons, which results in slowing or complete block of impulse transmission. It is also associated with para- or quadriparesis, sensory disturbances, bowel and bladder dysfunction and gait abnormalities.

Encephalitogenic

Having a propensity to cause inflammation of the brain.

Gadolinium-enhancing lesions

A contrast agent that leaks into the parenchyma in areas of blood–brain barrier breakdown. These regions are seen as bright signal with specific magnetic resonance sequences and are thus 'enhanced' by gadolinium, indicating pathology.

Leber's hereditary optic neuropathy

(LHON). A disease caused by a mutation in mitochondrial DNA. It is characterized by bilateral, painless, gradual visual loss starting in young adult life that is caused by degeneration of retinal ganglion cells and optic nerves.

Leukoencephalopathy

A generic term referring to pathology mainly involving white matter tracts of the brain (from Greek leukos: white).

Relapse

New neurological signs and symptoms, new lesions on magnetic resonance scanning.

Relapsing–remitting MS

The most common presentation of MS. It is characterized by repeated relapses that may last from weeks to months, followed by complete or incomplete clinical improvement.

Tumefactive

Characterized by pronounced swelling, occupying additional volume within the brain, thereby pushing aside and frequently compromising adjacent normal structures.

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Stys, P., Zamponi, G., van Minnen, J. et al. Will the real multiple sclerosis please stand up?. Nat Rev Neurosci 13, 507–514 (2012). https://doi.org/10.1038/nrn3275

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