This has important consequences for studying the clinical correlates of gray matter damage. However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage in MS has considerably improved.
Unfortunately, imaging of pathology in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques. Several studies subsequently demonstrated that the histopathology of gray matter lesions differs from that of white matter lesions. Gray matter damage was shown to be frequent and extensive, and more pronounced in the progressive disease phases. 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 21 st century that the true extent and importance of gray matter pathology in MS was finally recognized. At the early onset of the 20 th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis (MS).
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