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Griffiths et al. Neuroimmunol Neuroinflammation 2020;7:51-67 Neuroimmunology
DOI: 10.20517/2347-8659.2019.21 and Neuroinflammation

Original Article Open Access

Substantial subpial cortical demyelination
in progressive multiple sclerosis: have we

underestimated the extent of cortical pathology?

Lauren Griffiths , Richard Reynolds , Rhian Evans , Ryan J. Bevan , Mark I. Rees , Djordje Gveric ,
2
1,3
1
1
2
1
James W. Neal , Owain W. Howell 1,2
1
1 Institute of Life Sciences, Swansea University Medical School, Swansea University, Swansea SA2 8PP, UK.
2 Department of Brain Sciences, Faculty of Medicine, Imperial College London, London W5 3EH, UK.
3 Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales NSW 2006, Australia.
Correspondence to: Dr. Owain W. Howell, Institute of Life Sciences, Swansea University Medical School, Swansea University,
Singleton Park, Swansea, SA2 8PP, UK. E-mail: o.w.howell@swansea.ac.uk
How to cite this article: Griffiths L, Reynolds R, Evans R, Bevan RJ, Rees MI, Gveric D, Neal JW, Howell OW. Substantial subpial
cortical demyelination in progressive multiple sclerosis: have we underestimated the extent of cortical pathology? Neuroimmunol
Neuroinflammation 2020;7:51-67. http://dx.doi.org/10.20517/2347-8659.2019.21
Received: 13 Dec 2019 First Decision: 21 Jan 2020 Revised: 14 Feb 2020 Accepted: 27 Feb 2020 Published: 21 Mar 2020

Science Editor: Roberta Magliozzi Copy Editor: Jing-Wen Zhang Production Editor: Jing Yu

Abstract

Aim: Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease. Much of the
complex symptomatology relates to pathology outside the classic white matter plaque, whereby lesions of the
cortical grey matter, which are difficult to resolve by conventional clinical imaging, are in part predictive of outcome.
We investigated the extent of grey matter pathology in whole coronal macrosections to reassess the contribution of
cortical pathology to total demyelinating lesion area in progressive MS.

Methods: Twenty-two cases of progressive MS were prepared as whole bi-hemispheric macrosections for histology,
immunostaining and quantitative analysis of lesion number and relative area, leptomeningeal inflammation and
microglial/macrophage activation.

Results: Cortical grey matter demyelination was seen in all cases, which was more extensive than in white and deep
grey matter (hippocampus, thalamus and basal ganglia) and accounted for 0.8%-60.2% of the entire measurable
cortical ribbon. The pattern of cortical grey matter demyelination was predominantly subpial (mean 90.9%, range
60%-100%, of total cortical grey matter lesion area) and cases with the largest areas of subpial cortical lesions had
more and larger deep grey matter lesions, greater numbers of activated microglia/macrophages, both in lesions
as well as in normal cortical grey matter, together with elevated leptomeningeal inflammation and lymphoid-like

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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