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

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...

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Vydané v:	Brain (London, England : 1878) Ročník 144; číslo 6; s. 1646
Hlavní autori:	Pardini, Matteo, Brown, J William L, Magliozzi, Roberta, Reynolds, Richard, Chard, Declan T
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England 28.07.2021
Predmet:	meningeal inflammation magnetization transfer ratio multiple sclerosis neuropathology B cell follicle
ISSN:	1460-2156, 1460-2156
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Abstract	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.
AbstractList	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.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. 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.
Author	Pardini, Matteo Brown, J William L Chard, Declan T Reynolds, Richard Magliozzi, Roberta
Author_xml	– sequence: 1 givenname: Matteo surname: Pardini fullname: Pardini, Matteo organization: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy – sequence: 2 givenname: J William L surname: Brown fullname: Brown, J William L organization: Clinical Outcomes Research Unit (CORe), University of Melbourne, Melbourne, Australia – sequence: 3 givenname: Roberta surname: Magliozzi fullname: Magliozzi, Roberta organization: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK – sequence: 4 givenname: Richard surname: Reynolds fullname: Reynolds, Richard organization: Centre for Molecular Neuropathology, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore – sequence: 5 givenname: Declan T surname: Chard fullname: Chard, Declan T organization: National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, UK
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