Autoinflammatory grey matter lesions in humans: cortical encephalitis, clinical disorders, experimental models

In recent years, evidence has accumulated that grey matter abnormalities are common in many inflammatory central nervous system (CNS) disorders, such as multiple sclerosis (MS), which is by far the most frequent autoimmune-mediated CNS disease.

A recent study described comprehensively the pathology of grey matter lesions in early MS. In this study, cortical demyelination together with inflammation was frequently observed in early MS cases. This study and others serve as a basis for a model of the development of cortical MS lesions in which several consecutive events may be involved. After the activation of T cells, which may open the blood-brain barrier, the humoral immune system may mediate the inflammatory process. The inflammation may become chronic through the involvement of activated glial cells and the persistence of immune cells in the meninges.Apart from MS, other grey matter CNS disorders exist in which antibodies against neuronal structures contribute to pathophysiological events such as in limbic encephalitis. Humoral and adaptive immunity mediates the pathophysiology of Rasmussen encephalitis.

This review focuses on the difference between inflammatory grey matter and white matter lesions. New insights into inflammatory grey matter lesions in MS and other CNS inflammatory processes such as limbic encephalitis are discussed.