Meningeal and cortical grey matter pathology in multiple sclerosis

Bogdan F Gh Popescu,Claudia F Lucchinetti

doi:10.1186/1471-2377-12-11

Abstract

Although historically considered a disease primarily affecting the white matter of the central nervous system, recent pathological and imaging studies have established that cortical demyelination is common in multiple sclerosis and more extensive than previously appreciated. Subpial, intracortical and leukocortical lesions are the three cortical lesion types described in the cerebral and cerebellar cortices of patients with multiple sclerosis. Cortical demyelination may be the pathological substrate of progression, and an important pathologic correlate of irreversible disability, epilepsy and cognitive impairment. Cortical lesions of chronic progressive multiple sclerosis patients are characterized by a dominant effector cell population of microglia, by the absence of macrophagic and leukocytic inflammatory infiltrates, and may be driven in part by organized meningeal inflammatory infiltrates. Cortical demyelination is also present and common in early MS, is topographically associated with prominent meningeal inflammation and may even precede the appearance of classic white matter plaques in some MS patients. However, the pathology of early cortical lesions is different than that of chronic MS in the sense that early cortical lesions are highly inflammatory, suggesting that neurodegeneration in MS occurs on an inflammatory background and raising interesting questions regarding the role of cortical demyelination and meningeal inflammation in initiating and perpetuating the disease process in early MS.

Highlights

Historically considered a disease primarily affecting the white matter of the central nervous system, recent pathological and imaging studies have established that cortical demyelination is common in multiple sclerosis and more extensive than previously appreciated
While white matter lesion load has been able to explain only part of the clinical deficits seen in Multiple sclerosis (MS) patients, cognitive impairment and seizures could be better explained by pathological processes affecting the grey matter [7,8,9,10,11,12,13,14]
We consider lesions affecting all 6 cortical layers with only marginal involvement of the white matter as subpial, rather than leukocortical demyelinated lesions [27]. Their subpial nature is supported by the centrifugal extension of the lesion from the pial surface into the cortex; the involvement of all cortical layers; the vast area of demyelination within the cortex with only limited involvement of the subcortical white matter; and the fact that the center of the lesion is in the grey and not in the white matter [27] as most often reported for leukocortical lesions [4,16]

Summary

Introduction

Historically considered a disease primarily affecting the white matter of the central nervous system, recent pathological and imaging studies have established that cortical demyelination is common in multiple sclerosis and more extensive than previously appreciated. Type 2 lesions involve all cortical layers without affecting the underlying white matter. Studying autopsy material from patients with chronic MS, the authors described four cortical lesion types [4,16].

Results

Conclusion