What is the pathophysiology of multiple system atrophy (MSA)?

Updated: Sep 24, 2018
  • Author: Stephen M Bloomfield, MD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

Answer

Although the exact cause of MSA evades understanding, many pathophysiologic mechanisms have been uncovered.

Iron and ferritin levels appear to be increased in the substantia nigra and striatum. Oligodendroglial and microglial cells are predominantly involved, with neurons and astrocytes relatively spared. Iron levels in the putamen are 5 times higher than normal and are associated with coarse electron-dense granules and fine granular and fibrillary material in lamellated structures. This excessive iron accumulation correlates with the signal voids noted in these structures on MRI. Excessive iron may produce neurotoxicity because of its role in oxidation and reduction reactions. This type of oxidative stress is postulated to be involved in various neurodegenerative disorders. Iron also promotes fibril formation from alpha-synuclein that may be responsible for the formation of Glial cytoplasmic inclusions (GCIs).

Genetic susceptibility involving various genetic markers has been examined without confirmation. Genetic markers for previously identified spinocerebellar disorders are not found in patients with MSA. Mitochondrial chain function in the substantia nigra and platelets of patients with MSA are similar to those of age-matched controls.


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