Cortical demyelination in multiple sclerosis: A substrate for cognitive deficits?

doi:10.1016/j.jns.2005.09.021

Journal of the Neurological Sciences

Volume 245, Issues 1–2, 15 June 2006, Pages 123-126

https://doi.org/10.1016/j.jns.2005.09.021 Get rights and content

Abstract

Recent studies highlight cortical demyelinated lesions as a feature of multiple sclerosis (MS) pathology, which has received little attention so far. Here, we describe that cortical plaques are frequent and widespread, in particular in patients with primary or secondary progressive MS. Furthermore, we describe that certain cortical areas, such as the cingulated gyrus, the insular cortex and the temporobasal cortex, are more affected than others. These data indicate that cortical lesions have to be considered as an additional pathological substrate for cognitive dysfunction in MS patients.

Introduction

Multiple sclerosis is generally regarded as an inflammatory demyelinating disease, which leads to focal demyelinated plaques in the white matter [1], although some previous studies have shown that demyelinated plaques may also be present in the cerebral cortex and in brain stem nuclei [2], [3], [4]. Cortical lesions so far received little attention, since they are hardly visible in conventional myelin stains. This changed when alterations in myelin in the grey matter and in particular within the cortex were reliably detected by using sensitive immunocytochemical techniques [5], [6]. Three distinct lesion types in the cortex have been delineated: cortico-subcortical compound lesions (located at the border between cortex and white matter and affecting both white and grey matter), small perivascular intracortical lesions (which affect per definition only the cortex) and band-like subpial demyelination (usually affecting layers I–IV of the cerebral cortex), extending over large distances of the cortical ribbon [4], [5], [6].

So far, little is known regarding the functional consequences of cortical plaques in MS. There is some neuronal and axonal injury in cortical plaques, although it is not known whether neuronal damage affects different types of plaques equally [6]. The pathological mechanisms that lead to demyelination in the cortex are also unclear, as it has been shown that T-cell driven inflammation within cortical plaques is not more pronounced than in normal cortex [7]. In the present study we show that cortical involvement in multiple sclerosis patients is extensive and shows a hierarchical pattern, which is related to the extent of cortical demyelination.

Section snippets

Materials and methods

The study was performed on archival autopsy material from 27 MS patients with different disease manifestations (acute MS: n = 6; relapsing–remitting MS: n = 5; secondary progressive MS: n = 10; and primary progressive MS: n = 6). After fixation with formalin, brains were dissected and large hemispheric or double hemispheric blocks of forebrain tissue were embedded in paraffin. Sections were stained with hematoxylin/eosin and Luxol fast blue for myelin. To visualize cortical demyelination, complete

The type of cortical demyelination differs between different stages or courses of MS

Cortico-subcortical compound lesions and small intracortical perivenous lesions were present in all stages or courses of multiple sclerosis, including acute MS, RRMS, PPMS and SPMS. These lesions made only a small contribution to the total cortical lesion load in the global MS sample, although they were the dominant lesions in patients with acute and relapsing MS.

Band-like subpial demyelination was mainly found in patients with primary or secondary progressive MS. Such lesions were either

Discussion

Our study shows that cerebral cortex can be extensively involved in multiple sclerosis patients, in particular in the progressive phase of the disease. In addition, we have noted that cortical lesions are not evenly distributed throughout the brain, but that there are cortical areas, which are affected more severely compared to others. The main questions, which arise from these observations, are what is the reason of this different regional vulnerability of the cerebral cortex and what are the

Acknowledgements

This study was supported by the Fonds zur Förderung der wissenschaftlichen Forschung, Austria, Project P16848-B02.

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Cortical demyelination in multiple sclerosis: A substrate for cognitive deficits?

Abstract

Introduction

Section snippets

Materials and methods

The type of cortical demyelination differs between different stages or courses of MS

Discussion

Acknowledgements

Neuroimage

Neuroimage

Neuroimage

Multiple sclerosis

N Engl J Med

The distribution of plaques in the cerebrum in multiple scleosis

J Neurol Neurosurg Psychiatry

The neuropathology of multiple sclerosis

Cortical lesions in multiple sclerosis

Brain

Subpial demyelination in the cerebral cortex of multiple sclerosis patients

J Neuropathol Exp Neurol

Transsected neurites, apoptotic neurons and reduced inflammation in cortical multiple sclerosis lesions

Ann Neurol

Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration

Mult Scler

Destruction of neurons by cytotoxic T cells: a new pathogenic mechanism in Rasmussen's encephalitis

Ann Neurol