Grey Matter Pathology in Multiple Sclerosis

Abstract

The aim of our study is to evaluate the extent and distribution of grey matter demyelinating lesions in multiple sclerosis (MS), addressing also neuronal loss and synaptic loss. Whole coronal sections of 6 MS brains and 6 control brains were selected. Immunohistochemistry was performed for myelin basic protein, neurofilaments, synaptophysin, ubiquitin, and activated caspase-3. Neuronal density and optical density of synaptophysin staining were estimated in cortical lesions and compared with those observed in corresponding areas of normal (i.e. nondemyelinated) cortex in the same section. Demyelinating lesions were observed in the cerebral cortex, in the thalamus, basal ganglia, and in the hippocampus. The percentage of demyelinated cortex was remarkable in 2 cases of secondary progressive MS (48% and 25.5%, respectively). Neuronal density was significantly reduced in cortical lesions (18-23% reduction), if compared with adjacent normal cortex, in the 2 cases showing the higher extent of cortical demyelination; in the same cases, very rare apoptotic neurons expressing caspase-3 were observed in cortical lesions and not in adjacent normal cortex. No significant decrease in optical density of synaptophysin staining was observed in cortical lesions. Grey matter demyelination and neuronal loss could contribute to disability and cognitive dysfunctions in MS.

An Autopsy Case of the Marburg Variant of Multiple Sclerosis (Acute Multiple Sclerosis)

“…The level of IL-9 is significantly increased in patients with atopic myelitis; however, this value was not elevated in our patient (17,18). Although MS is regarded to be a white matter disease, recent histopathological studies of early MS (25)(26)(27)(28)(29) have revealed lesions in the leptomeninges and gray matter to be important initial targets of the MS process. Furthermore, re-cent studies have extended the earlier concept of MS, namely that the inflammation observed in MS is principally mediated by CD4+ type I helper T-cells.…”

Focal cortical atrophy in multiple sclerosis: Relation to lesion load and disability

“…If cortical atrophy is the result of axonal transection by WM lesions, then highly connected regions should be more vulnerable than regions with relatively fewer connections. However, it is also possible that these gray matter regions are somehow intrinsically more vulnerable to direct involvement by the disease; indeed, histopathological studies have demonstrated that the cingulate gyrus, temporal lobe, and insula generally show a higher prevalence of cortical demyelinated lesions than other areas (Bö et al, 2003;Vercellino et al, 2005;Kutzelnigg and Lassmann, 2006). Two studies on relatively small numbers (n = 30 and 26) of MS patients reported a correlation between fractional GM volume and total WM lesion volume, but not disability (Ge et al, 2001;Chard et al, 2002).…”

Ultra-High-Field MRI Visualization of Cortical Multiple Sclerosis Lesions with T2 and T2*: A Postmortem MRI and Histopathology Study

“…This seems low, but the coronal sections were sampled from more frontal regions of the brain, a preferential area for cortical pathology, 22,23 but not far for WMLs, which are more frequently located periventricular.…”