Chapter 1 - Multiple Sclerosis Pathology: Inflammation Versus Neurodegeneration

Abstract

Multiple sclerosis (MS) is not only a disease with focal demyelinated lesions in the white matter, but demyelination in the gray matter is prominent, especially in the progressive stage of the disease. In addition, diffuse injury of the normal-appearing white and gray matter develops in part independently from focal lesions. MS is a chronic inflammatory disease of the central nervous system throughout all stages of the disease. Inflammation is dominated by major histocompatibility complex Class I restricted T-cells. Active demyelination and neurodegeneration are associated with T-cell and B-cell infiltrates in the perivascular space and the meninges and less prominently with diffuse lymphocyte infiltration of the central nervous system tissue. Activated microglia are seen in close contact with degenerating myelin sheaths, axons, and neurons. Different immunological mechanisms seem to be involved in the induction of tissue injury, but microglia activation associated with oxidative injury and mitochondrial damage appears to play a dominant role.