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The neuropathological basis of clinical progression in multiple sclerosis

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Abstract

Multiple sclerosis is the major inflammatory condition affecting the central nervous system (CNS) and is characterised by disseminated focal immune-mediated demyelination. Demyelination is accompanied by variable axonal damage and loss and reactive gliosis. It is this pathology that is thought to be responsible for the clinical relapses that often respond well to immunomodulatory therapy. However, the later secondary progressive stage of MS remains largely refractory to treatment and it is widely suggested that accumulating axon loss is responsible for clinical progression. Although initially thought to be a white matter (WM) disease, it is increasingly apparent that extensive pathology is also seen in the grey matter (GM) throughout the CNS. GM pathology is characterised by demyelination in the relative absence of an immune cell infiltrate. Neuronal loss is also seen both in the GM lesions and in unaffected areas of the GM. The slow progressive nature of this later stage combined with the presence of extensive grey matter pathology has led to the suggestion that neurodegeneration might play an increasing role with increasing disease duration. However, there is a paucity of studies that have correlated the pathological features with clinical milestones during secondary progressive MS. Here, we review the contributions that the various types of pathology are likely to make to the increasing neurological deficit in MS.

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Acknowledgments

Work described in this review was funded by the Multiple Sclerosis Society (Grant No. 747/02 to RR, FR and RN) and the Medical Research Council (Grant No. G0700356 to RR and OH).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Wolfson Neuroscience Laboratories, Division of Experimental Medicine, UK Multiple Sclerosis Tissue Bank, Centre for Neuroscience, Imperial Faculty of Medicine College London, Hammersmith Hospital Campus, London, W12 0NN, UK

    Richard Reynolds, Federico Roncaroli, Richard Nicholas, Bishan Radotra, Djordje Gveric & Owain Howell

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  1. Richard Reynolds
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  2. Federico Roncaroli
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  3. Richard Nicholas
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  4. Bishan Radotra
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Correspondence to Richard Reynolds.

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R. Reynolds and F. Roncaroli contributed equally to the review.

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Reynolds, R., Roncaroli, F., Nicholas, R. et al. The neuropathological basis of clinical progression in multiple sclerosis. Acta Neuropathol 122, 155–170 (2011). https://doi.org/10.1007/s00401-011-0840-0

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