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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
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Surface-in pathology in multiple sclerosis: a new view on pathogenesis?

Matteo Pardini1,2, J William L Brown1,3,4, Roberta Magliozzi5,6

  • 1NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.

Brain : a Journal of Neurology
|April 20, 2021
PubMed
Summary

Multiple sclerosis (MS) lesions show a distinct "surface-in" pattern in the central nervous system (CNS). This distribution, particularly in grey matter, suggests inflammation-related factors may drive MS pathology.

Keywords:
B cell folliclemagnetization transfer ratiomeningeal inflammationmultiple sclerosisneuropathology

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Area of Science:

  • Neuroimmunology
  • Neurodegeneration
  • Central Nervous System (CNS) Disorders

Background:

  • Multiple sclerosis (MS) affects the CNS, with lesion distribution not being uniform.
  • White matter lesions are often periventricular, while grey matter lesions concentrate in the subpial cortex.
  • Neuronal loss in the cortex is more pronounced in superficial layers.

Purpose of the Study:

  • To review the 'surface-in' spatial distribution of MS abnormalities.
  • To explore the implications for understanding MS pathogenesis.
  • To consider the impact on developing treatments for MS.

Main Methods:

  • Review of existing literature on MS lesion distribution.
  • In vivo imaging techniques, such as magnetization transfer ratio (MTR), used to study grey and white matter abnormalities.
  • Analysis of spatial gradients in MTR around ventricles and in cortical grey matter.

Main Results:

  • A reproducible 'surface-in' gradient of grey matter damage in MS, with greater neuronal loss in outer cortical layers.
  • Similar MTR gradients observed in grey and white matter around ventricles, with maximal abnormalities near the ventricular surface.
  • Evidence supports soluble factors from meningeal inflammation, released into cerebrospinal fluid (CSF), as a potential cause for these gradients.

Conclusions:

  • The 'surface-in' distribution of MS lesions is a key feature of the disease.
  • Understanding this spatial pattern is crucial for elucidating pathogenic mechanisms.
  • This knowledge may inform the development of targeted MS therapies.