Abstract
At the early onset of the 20th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis (MS). However, as white matter pathology long received predominant attention in this disease, and histological staining techniques for detecting myelin in the gray matter were suboptimal, it was not until the beginning of the 21st century that the true extent and importance of gray matter pathology in MS was finally recognized. Gray matter damage was shown to be frequent and extensive, and more pronounced in the progressive disease phases. Several studies subsequently demonstrated that the histopathology of gray matter lesions differs from that of white matter lesions. Unfortunately, imaging of pathology in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques. However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage in MS has considerably improved. This has important consequences for studying the clinical correlates of gray matter damage. In this review, we provide an overview of what has been learned about imaging of gray matter damage in MS, and offer a brief perspective with regards to future developments in this field.
Highlights
For many years, focal inflammatory demyelination in the white matter (WM) was considered the most important pathological ‘hallmark’ of multiple sclerosis (MS)
▪ gray matter (GM) pathology is present in all stages of the disease, but is more prominent in SPMS and PPMS compared to relapsing remitting MS patients (RRMS);
▪ Cortical lesions have been difficult to visualize with conventional magnetic resonance imaging (MRI), but due to newer imaging techniques lesion detection improved;
Summary
Focal inflammatory demyelination in the white matter (WM) was considered the most important pathological ‘hallmark’ of multiple sclerosis (MS). Despite their under representation on MRI, cortical lesions were shown to be clinically relevant Both imaging and histopathology studies showed that GM damage in MS is not limited to the neocortex; the cerebellum, spinal cord, and non-neocortical GM structures are affected as well. The function of specific GM structures or functional systems, as well as functional and structural connectivity changes within the brain can be imaged with MRI With all these different imaging techniques to visualize GM pathology in vivo, it remains to be determined which image modality, or combination of imaging modalities, best explains or predicts clinical symptomatology, and whether these techniques can be reliably used to monitor future treatment effects. Understanding of the role of GM pathology in MS in the near future
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