Pathology of multiple sclerosis and related inflammatory demyelinating diseases

This article provides a comprehensive overview of the pathology of multiple sclerosis (MS), including recent insights into its molecular neuropathology and immunology. It shows that all clinical manifestations of relapsing and progressive MS display the same basic features of pathology, such as chronic inflammation, demyelination in the white and gray matter, and diffuse neurodegeneration within the entire central nervous system. However, the individual components of the pathological spectrum vary quantitatively between early relapsing and late progressive MS. Widespread confluent and plaque-like demyelination with oligodendrocyte destruction is the unique pathological hallmark of the disease, but axonal injury and neurodegeneration are additionally present and in part extensive. Remyelination of existing lesions may occur in MS brains; it is extensive in a subset of patients, while it fails in others. Active tissue injury in MS is always associated with inflammation, consistent with T-cell and macrophage infiltration and microglia activation. Recent data suggest that oxidative injury and subsequent mitochondrial damage play a major pathogenetic role in neurodegeneration. Finally we discuss similarities and differences of the pathology between classical MS and other inflammatory demyelinating diseases, such as neuromyelitis optica, concentric sclerosis, or acute disseminated encephalomyelitis.