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Page 64 Griffiths et al. Neuroimmunol Neuroinflammation 2020;7:51-67 I http://dx.doi.org/10.20517/2347-8659.2019.21

interest, meaning that we could not, for example, report lesion measures for separate deep GM structures.
Nevertheless, the use of whole coronal sections reduces observer variation between individual cases,
increases the accuracy of observations, and ensures comparisons between different forebrain areas, which
are invaluable for the study of this heterogeneous disease.

In conclusion, our quantitative histological analysis revealed global grey matter demyelination and
meningeal inflammation to be substantial in a subset of progressive MS brains. Cases defined by a
substantial cortical GML load displayed greater microglia/macrophage activation, larger areas of deep
grey matter pathology but little change in white matter lesion area, which highlights the partially separate
pathogenetic mechanisms of lesion evolution (or susceptibility to damage) in these compartments. The
distribution of subcortical and deep GML in MS is consistent with the presence of soluble proinflammatory
factors in the subarachnoid space and ventricular CSF and furthers the need to identify companion
biomarkers of cortical pathology to aid patient monitoring and therapeutic choice.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study: Griffiths L, Reynolds R, Howell OW
Performed data analysis, interpretation and contributed to writing the manuscript and approved the final
submitted document: Griffiths L, Reynolds R, Evans R, Bevan RJ, Rees MI, Gveric D, Neal JW, Howell OW

Availability of data and materials
Data generated during the current study is available on reasonable request.

Financial support and sponsorship
The UK MS Society Tissue Bank (www.ukmstissuebank.imperial.ac.uk) supplied the post-mortem samples
used in this study and is supported by the Multiple Sclerosis Society of Great Britain and Northern Ireland.
The authors would like to thank members of the UK MS Tissue Bank for their invaluable assistance. This
work was supported by the St. Davids Medical Foundation, the British Neuropathological Society and the
Medical Research Council (G0700356). Reynolds R has received speaking honoraria from Roche, Novartis
and ECTRIMS and grant funding from MedImmune plc. Howell OW has received travel reimbursement
or speaking honoria (paid to Swansea University) from Roche, the Neurology Academy and ECTRIMS. All
other authors have no relevant disclosures.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
The use of human post mortem tissue is covered by UK Research Ethics committee approval (study
approval number 08/MRE09/31+5).

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

REFERENCES
1. Reynolds R, Roncaroli F, Nicholas R, Radotra B, Gveric D, et al. The neuropathological basis of clinical progression in multiple sclerosis.
Acta Neuropathol 2011;122:155-70.