Multiple System Atrophy

Pathology

Neurodegeneration in MSA-P is most prominent in the striatonigral system, while in MSA-C it is more marked in the olivopontocerebellar system. Autonomic system involvement is accompanied by cell loss in the dorsomotor nucleus of the vagus nerve, the locus coeruleus, and the ventrolateral medulla, as well as parasympathetic preganglionic nuclei in the spinal cord. Other cell populations may also be affected.

The pathologic hallmark of MSA is the presence of cytoplasmic inclusion bodies in glial cells of the basal ganglia, supplementary and primary motor cortices, reticular formation, and pontocerebellar system. These inclusions contain ubiquitin, tau, and alpha-synuclein. Glial cytoplasmic inclusions are definitive for the diagnosis of MSA. The discovery of alpha-synuclein in MSA inclusions linked the disease with Parkinson's disease and Lewy body dementia, together known as "synucleinopathies." The pathogenic significance of the inclusions, and how an excess of protein is involved in the disease process, is unknown.