Multiple System Atrophy

Abstract

Multiple system atrophy (MSA) is an uncommon but well-recognized disease entity that both neurologists and urologists may encounter. The term MSA was introduced by Graham and Oppenheimer in 1969 to describe a disorder of unknown cause affecting extrapyramidal, cerebellar, and autonomic pathways [1] MSA includes the disorders previously called striatonigraldegeneration (SND) [2], sporadic olivopontocerebellar atrophy (OPCA) [3], and Shy–Drager syndrome [4]. The discovery in 1989 of glial cytoplasmic inclusions in the brains of patients with MSA [5] provided a pathological marker for the disorder (akin to Lewy bodies in idiopathic Parkinson’s disease (IPD)) and confirmed that SND, OPCA, and Shy–Drager syndrome are the same disease with differing clinical presentations. Immunocytochemistry showed that the glial cytoplasmic inclusions of MSA are ubiquitin-, tau-, and alpha-synuclein (SNCA)-positive, possibly representing a cytoskeletal alteration in glial cells that results in neuronal degeneration [6, 7]. SNCA is a presynaptic neuronal protein encoded by the SNCA gene located on chromosome 4. This protein appears to play a role in dopamine and other neurotransmitter metabolism, vesicle trafficking, modification of synaptic transmission, and regulation of membrane permeability. In contrast, pathologically increased expression and abnormal conformation of SNCA are reported to reduce neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis [6, 7] Familial occurrence is estimated to account for 1.6% of all cases, and data on such cases are being accumulated to identify candidate genes for this disorder, including SNCA, MAPT (microtubule-associated protein tau), etc.