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Updated: Apr 6, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Pathological differences between white and grey matter multiple sclerosis lesions
Marloes Prins1, Emma Schul1, Jeroen Geurts1
1Department of Anatomy and Neurosciences.
Abstract:
Multiple sclerosis (MS) is a debilitating disease characterized by demyelination of the central nervous system (CNS), resulting in widespread formation of white matter lesions (WMLs) and grey matter lesions (GMLs). WMLs are pathologically characterized by the presence of immune cells that infiltrate the CNS, whereas these immune cells are barely present in GMLs. This striking pathological difference between WMLs and GMLs raises questions about the underlying mechanism. It is known that infiltrating leukocytes contribute to the generation of WMLs; however, since GMLs show a paucity of infiltrating immune cells, their importance in GML formation remains to be determined. Here, we review pathological characteristics of WMLs and GMLs, and suggest some possible explanations for the observed pathological differences. In our view, cellular and molecular characteristics of WM and GM, and local differences within WMLs and GMLs (in particular, in glial cell populations and the molecules they express), determine the pathway to demyelination. Further understanding of GML pathogenesis, considered to contribute to chronic MS, may have a direct impact on the development of novel therapeutic targets to counteract this progressive neurological disorder.
Insights
Multiple sclerosis causes central nervous system demyelination, forming white matter lesions (WMLs) and grey matter lesions (GMLs). Differences in immune cell infiltration suggest distinct pathogenic mechanisms for WMLs and GMLs.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Multiple sclerosis (MS) is a neuroinflammatory disease causing demyelination in the central nervous system (CNS).
- Lesions in MS are categorized as white matter lesions (WMLs) and grey matter lesions (GMLs), exhibiting distinct pathological features.
- WMLs are characterized by significant immune cell infiltration, while GMLs show a paucity of such cells, posing questions about their formation.
Purpose of the Study:
- To review and compare the pathological characteristics of WMLs and GMLs in MS.
- To explore potential mechanisms underlying the observed pathological differences between WMLs and GMLs.
- To highlight the importance of understanding GML pathogenesis for developing new therapeutic strategies in chronic MS.
Main Methods:
- Review of existing pathological data and literature on WMLs and GMLs in multiple sclerosis.
- Comparative analysis of cellular and molecular features within white matter (WM) and grey matter (GM) lesions.
- Discussion of the role of glial cells and their expressed molecules in demyelination pathways.
Main Results:
- Significant differences in immune cell infiltration exist between WMLs and GMLs.
- Cellular and molecular characteristics of WM and GM, including glial populations, likely dictate distinct demyelination pathways.
- GMLs, despite limited immune cell presence, are implicated in the chronic progression of MS.
Conclusions:
- The distinct pathological profiles of WMLs and GMLs suggest unique underlying mechanisms.
- Local factors within CNS tissues, particularly glial cell activity, are crucial in determining lesion type and progression.
- Further research into GML pathogenesis is essential for advancing therapeutic interventions against progressive MS.
