Grey matter pathology in multiple sclerosis

Abstract

Multiple sclerosis (MS) has been classically regarded as a white matter disease. However, recent histopathological studies have convincingly shown that grey matter regions are also heavily affected. Grey matter damage starts early in the disease and substantially affects clinico-cognitive functioning. Detection of cortical grey matter lesions by use of standard MRI techniques has proved challenging, and more advanced techniques are needed. At present, the causes of grey matter damage are unclear. We review several exciting new hypotheses on grey matter pathogenesis, including meningeal inflammation as a cause of subpial cortical damage, but also selective vulnerability of neuronal subpopulations, growth factor dysregulation, glutamate excitotoxicity, mitochondrial abnormalities, and the "use-it-and-lose-it" principle. These hypotheses remain to be validated over the coming years, and could substantially affect our current views on MS pathogenesis.

Fractal dimension analysis of grey matter in multiple sclerosis

“…In addition, GM histological abnormalities increase in MS over time [8], which might account for the significant increase of the FD in the transition from FAMS to RRMS. The topography of GM damage in MS drives the appearance of functional deficits [31,32].…”

“…Although lesions involving the white matter (WM) are well recognized, recent studies have indicated extensive damage of the grey matter (GM) in MS, including microglia activation, cortical demyelination, and axonal, synaptic, and neuronal loss [2][3][4][5][6][7]. Recently, the extension and pathological basis of GM pathology have been highlighted from pathological and neuroimaging studies [8]. GM atrophy, extensively reported in MS, begins early and evolves over the course of the disease, and GM tissue volumes are lower in MS patients than in control subjects [9][10][11][12][13][14][15].…”

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

“…[121][122][123][124][125][126] Several MRI techniques, including double inversion recovery and phase sensitive inversion recovery, have been used to detect, score and interpret cortical grey matter lesions, but these applica tions lack standardization. [127][128][129] Advanced, quanti tative imaging techniques may also acquire a central role for evaluating the course of MS pathology in the near future.…”

Genetic Correlations of Brain Lesion Distribution in Multiple Sclerosis: An Exploratory Study

“…43 From postmortem studies we know that gray matter lesions are extensively present in patients with MS, 43 and it can be expected that a different genetic background may influence the lesion distribution between the white and gray matter compartments, as well as the anatomic distribution within the white and gray matter. Total brain lesion volume seems to be an important covariate in LPM analyses.…”