becomes small and spidery Cerebellar dysfunction - difficulty coordinating movement and balance Autonomic nervous system dysfunction - impaired automatic body functions, including one, some, or all of the following: postural or orthostatic hypotension, resulting in dizziness or fainting upon standing up urinary incontinence or urinary retention impotence constipation vocal cord paralysis dry mouth and skin trouble regulating body temperature due to sweating deficiency in all parts of the body loud snoring, abnormal breathing or inspiratory stridor during sleep other sleep disorders including sleep apnea, REM behavior disorder double vision muscle twitches Cognitive impairment Genetics One study found a correlation between the deletion of genes in a specific genetic region and the development of MSA in a group of Japanese patients. The region in question includes the SHC2 gene which, in mice and rats, appears to have some function in the nervous system. The authors of this study hypothesized that there may be a link between the deletion of the SHC2 and the development of MSA. A follow-up study was unable to replicate this finding in American MSA patients. The authors of the U.S. study concluded that "Our results indicate that SHC2 gene deletions underlie few, if any, cases of well-characterized MSA in the US population. This is in contrast to the Japanese experience reported by Sasaki et al., likely reflecting heterogeneity of the disease in different genetic backgrounds." Another study investigated the frequency of RFC1 intronic repeat expansions, a phenomenon implicated in CANVAS; a disease with a diagnostic overlap with MSA. The study concluded that these repeats were absent in pathologically confirmed MSA, suggesting an alternative genetic cause. Pathophysiology Multiple system atrophy can be explained as cell loss and gliosis or a proliferation of astrocytes in damaged areas of the central nervous system. This damage forms a scar which is then termed a glial scar. The presence of inclusion bodies known as Papp–Lantos bodies, in the movement, balance, and autonomic-control centres of the brain are the defining histopathologic hallmark of MSA. The major filamentous component of Papp-Lantos bodies, glial and neuronal cytoplasmic inclusions, is alpha-synuclein. Mutations in this substance may play a role in the disease. The conformation of the alpha-synuclein is different from that of alpha-synuclein in Lewy bodies. The disease probably starts with an oligodendrogliopathy. Tau proteins have been found in some glial cytoplasmic inclusion bodies. Diagnosis Clinical Clinical diagnostic criteria were defined in 1998 and updated in