Multiple system atrophy (MSA) is an intractable neurodegenerative disease characterized by autonomic failure in addition to various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. MSA encompasses striatonigral degeneration, olivopontocerebellar atrophy, and Shy-Drager syndrome, which were originally described as independent clinicopathological entities. The coexistence was detected later, and these conditions were regarded as nosologically allied. The disease is characterized by the accumulation of alpha-synuclein fibrils in oligodendrocytes that form glial cytoplasmic inclusions (GCI), a neuropathological hallmark and central player in the pathogenesis of MSA. Although MSA is widely considered to be a nongenetic disorder, genetic mutations of the COQ2 gene have been linked to MSA as identified in Japanese families.
