Pathogenesis of brain and spinal cord atrophy in multiple sclerosis.
For more than a century, multiple sclerosis was viewed as a disease process characterized by oligodendrocyte and myelin loss, and research into the pathogenesis of multiple sclerosis was mainly focused on the mechanisms of inflammation. However, with development of more sophisticated neuroimaging and molecular biology techniques, attention has shifted to new aspects of pathogenesis of multiple sclerosis: axonal loss and neurodegeneration. Evidence is increasing that tissue destruction, primarily axonal loss and neurodegeneration, is a key element in the pathogenesis of multiple sclerosis. In addition, it is now known that brain and spinal cord atrophy begins early in the disease process of multiple sclerosis and advances relentlessly throughout the course of the disease. Cumulative data suggest that axonal loss is the major determinant of progressive neurologic disability in patients with multiple sclerosis. Magnetic resonance imaging and magnetic resonance spectroscopy in patients with multiple sclerosis for < 5 years indicate brain atrophy and loss of axonal integrity. Neurodegeneration and axonal loss in patients with multiple sclerosis are initially accompanied by a local response from oligodendrocyte progenitor cells and some remyelination. However, these repair mechanisms eventually fail, and patients typically develop generalized brain atrophy, cognitive decline, and permanent disability. Although the exact mechanisms underlying central nervous system atrophy in patients with multiple sclerosis are largely unknown, evidence exists that atrophy may represent an epiphenomenon related to the effects of dynamic inflammation within the central nervous system, including demyelination, axonal injury, neuronal loss, Wallerian degeneration, and possibly iron deposition. This article summarizes the potential mechanisms involved in central nervous system atrophy in patients with multiple sclerosis.
Minagar
Alireza
A
Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA. aminag@lsuhsc.edu
Toledo
Eduardo Gonzalez
EG
Alexander
J Steven
JS
Kelley
Roger E
RE
D017209:Apoptosis; D001284:Atrophy; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009103:Multiple Sclerosis / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology*