AbstractPure autonomic failure (PAF) and multiple system atrophy (MSA) are representative neurodegerative diseases present with a severe autonomic dysfunction in the urinary, cardiovascular, and pupillary systems, as well as the gastrointestinal tract and skin/sweat glands. Clinically PAF is characterized by chronic progressive pure autonomic dysfunction occasionally associated with parkinsonism or cognitive dysfunction (Lewy body disease), whereas MSA is associated with cerebellar manifestation and/or parkinsonism. Pathology of both PAF and MSA is characterized by α‐synuclein deposition, but in PAF major involvement exists in the sympathetic ganglion and postganglionic autonomic nerve fibers, whereas MSA mainly affects the central autonomic system, such as the vagal nerve lateral nucleus, locus coeruleus, spinal cord medial lateral nucleus, and sacral Onuf's nucleus. Therefore, it is necessary to evaluate whether peripheral or central autonomic function is predominantly affected by the differential diagnosis of PAF and MSA. Autonomic dysfunction is also frequently present in patients with Parkinson's disease, but usually not so severe as in PAF or MSA. This review summarizes features of autonomic dysfunction in PAF and MSA.
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