Grey Matter Pathology in Multiple Sclerosis
Multiple sclerosis (MS) is a CNS disease histopathologically characterized by discrete areas of myelin, oligodendrocyte, and axonal loss . The etiology of MS is unknown, but environmental factors and multiple separate genetic loci contribute to disease susceptibility. MS lesions may occur in all CNS parenchymal areas; the predilection sites include the optic nerve, brainstem, spinal cord, periventricular white matter, and subcortical areas. Although MS is frequently called a white matter disease, there is also myelin in grey matter, and grey matter demyelination is extensive in chronic MS [2–7]. This was evidenced even in early pathology studies, using histochemical staining methods for myelin detection [8–11]. The extent of cortical demyelination in MS has been studied in vivo using MRI and post mortem using histochemical or immunohistochemical techniques. Conventional MRI techniques may not be sensitive for cortical lesions, however: in a comparison of postmortem MRI and histological examinations, only 2 of 14 histologically detectable cortical lesions were detected by MRI . In another, similar study none of the 39 cortical plaques identified histologically were detected by MRI, while in periventricular areas the maximum possible number of lesions detected by MRI often exceeded the number of histological plaques . A recent study found a low sensitivity of MRI for purely cortical lesions compared with the grey matter part of combined white matter/grey matter lesions . MRI sensitivity for deep grey matter lesions was slightly higher, at 10%–15% [7,12]. The reasons for the low sensitivity of conventional MRI could be (1) that the relaxation times of grey matter on T2-weighted images are close to the relaxation times of MS lesions, (2) partial volume effects due to the proximity to the CSF, and (3) less inflammation and edema in the grey matter lesions . “Normal-appearing grey matter” on MRI thus represents what proves histopathologically to be a mixture of grey matter lesions and nonlesional tissue. This makes it difficult to characterize the clinical significance of grey matter lesions by MRI. Nevertheless, the presence and extent of “juxtacortical” MS lesions on MRI have been correlated with cognitive loss, depression, and epilepsy [13–17].
KeywordsMultiple Sclerosis Grey Matter Myelin Basic Protein White Matter Lesion Cortical Lesion
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