Non-motor multiple system atrophy associated with sudden death: pathological observations of autonomic nuclei
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Multiple system atrophy (MSA) manifests as a combination of dysautonomia and motor symptoms/signs. However, rare cases presenting with autonomic failures in absence of motor symptoms/signs until their deaths have been reported and are referred to as non-motor MSA. To clarify pathological findings underlying non-motor MSA patients, we analyzed consecutively autopsied 161 patients with MSA. In results, four patients were identified as having non-motor MSA, who showed isolated autonomic disorders throughout their lives and had minimal pathological changes in the motor systems. We also identified two patients with pathologically minimal MSA, who had minimal pathological involvement in the motor systems and presented with definite parkinsonism and dysautonomia. Survival durations of the non-motor MSA patients were much shorter (1.3–2.0 years) than those of the classical MSA patients (3.0–7.0 years), and the causes of death were all sudden death. The medullary serotonergic neurons were severely involved in the non-motor MSA patients in comparison with the classical MSA patients. Also, one of the pathologically minimal MSA patients had died suddenly and exhibited marked involvement of the medullary serotonergic neurons. The involvement of the medullary catecholaminergic or cholinergic neurons did not differ in severities among the groups. We conclude that non-motor MSA may be a pathological variant of MSA that preferentially involves the medullary serotonergic neurons and autonomic systems in association with poor prognosis.
KeywordsMultiple system atrophy Autopsy Autonomic failure Sudden death
Study concept and design: Yuichi Riku, Hirohisa Watanabe, Mari Yoshida, and Gen Sobue. Acquisition of data: Yuichi Riku, Maya Mimuro, Hirohisa Watanabe, and Mari Yoshida. Analysis and interpretation of data: Yuichi Riku, Hirohisa Watanabe, Masahisa Katsuno, Mari Yoshida, and Gen Sobue. Drafting of the manuscript: Yuichi Riku. Administrative, technical, and material support: Yuichi Riku, Maya Mimuro, and Yasushi Iwasaki. Study supervision: Mari Yoshida, Hirohisa Watanabe, and Gen Sobue. We give special thanks to all the patients, their families, and the staff in the affiliated hospitals for providing the autopsy materials and clinical data.
Compliance with ethical standards
Conflict of interest
All authors declared that they have no potential conflict of interest.
The study was performed in accordance with the research ethical committees of Aichi Medical University.
This work was supported by Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health, Labour and Welfare of Japan.
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