Pathogenesis of Brain and Spinal Cord Atrophy in Multiple Sclerosis

Abstract

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.

Evidence for neuroprotection and remyelination using imaging techniques

“…Although the precise mechanisms are unknown, CNS atrophy appears to result from the effects of inflammation, leading to demyelination, neuroaxon injury, and Wallerian degeneration. 33 These pathologic substrates are both multifocal (present in MRI-visible lesions) and diffuse throughout the CNS. Imaging research has helped to clarify the relation between these dynamic inflammatory processes and loss of brain tissue.…”

Similar autobiographical memory impairment in long-term secondary progressive multiple sclerosis and Alzheimer's disease

“…These lesions and plaques affect the myelin sheath, thus impairing axonal propagation of the action potential. 10 While inflammatory demyelination has traditionally been seen as the main disease process in MS, axonal damage or loss is receiving increasing attention. 11 Grey matter damage may be the pathological correlate of the cognitive dysfunction that arises in 40-70% of patients with MS. 12 The topography of grey matter atrophy in MS differs among the MS subtypes: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS).…”

Two frequent polymorphisms of angiotensinogen and their association with multiple sclerosis progression rate

“…It is characterized by a destruction of myelin sheet of nerve fibers, axonal lost and neuronal degeneration [1,2].…”