Gray matter involvement in multiple sclerosis and neuromyelitis optica

Abstract

Multiple sclerosis (MS) and neuomyelitis optica (NMO) are the two main autoimmune and inflammatory diseases of the central nervous system. They have long been considered to be autoimmune diseases that primarily affect the white matter (WM). However, renewed interest in gray matter (GM) pathology is emerging. This review focuses on the current knowledge of the details of GM pathology, and its clinical aspects including cognitive impairment in MS and NMO. Patients with MS and NMO have similar cognitive profiles as represented by the latent start of impairment from a very early stage of the disease course. Pathological assessments show that substantial cortical demyelination is prominent in all stages or courses of MS, and cortical neurodegeneration is also present not only in cortical demyelination, but also in normal-appearing GM in MS. In contrast, cortical neurodegeneration is present in NMO and involves unique dynamics of astrocytes, but no cortical demyelination is seen in NMO. Thus, two distinct diseases, MS and NMO, each have unique characteristic features of pathological modalities in the brain. These important hallmarks of MS and NMO might influence neuronal and cognitive function in the brain, given different detrimental effects including cytokine diffusion, disruption of water homeostasis associated with aquaporin-4 dynamics, or other unidentified mechanisms. Although the cause of GM lesions in MS and NMO has not been fully determined, an increase in knowledge of the structure of GM lesions, and the pathomechanisms in MS and NMO brains will result in more targeted pharmacotherapeutic approaches to these diseases. © 2014 Japanese Society for Neuroimmunology.