Surface-in pathology in multiple sclerosis: a new view on pathogenesis?

Matteo Pardini, J. William L. Brown, Roberta Magliozzi, Richard Reynolds, Declan T. Chard

Research output: Contribution to journalArticlepeer-review


While multiple sclerosis can affect any part of the CNS, it does not do so evenly. In white matter it has long been recognized that lesions tend to occur around the ventricles, and grey matter lesions mainly accrue in the outermost (subpial) cortex. In cortical grey matter, neuronal loss is greater in the outermost layers. This cortical gradient has been replicated in vivo with magnetization transfer ratio and similar gradients in grey and white matter magnetization transfer ratio are seen around the ventricles, with the most severe abnormalities abutting the ventricular surface. The cause of these gradients remains uncertain, though soluble factors released from meningeal inflammation into the CSF has the most supporting evidence. In this Update, we review this 'surface-in' spatial distribution of multiple sclerosis abnormalities and consider the implications for understanding pathogenic mechanisms and treatments designed to slow or stop them.

Original languageEnglish
Pages (from-to)1646-1654
Number of pages9
JournalBrain : a journal of neurology
Issue number6
Publication statusPublished - Jul 28 2021


  • B cell follicle
  • magnetization transfer ratio
  • meningeal inflammation
  • multiple sclerosis
  • neuropathology

ASJC Scopus subject areas

  • Clinical Neurology


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