Objective: This study examined the distribution and longitudinal progression of sweat loss in patients with PAF.

Background: Pure autonomic failure (PAF) is an alpha-synucleinopathy with a 30–40% risk of phenoconversion to parkinson’s disease (PD), dementia with lewy bodies (DLB), or multiple system atrophy (MSA). While several biomarkers have been proposed to predict phenoconversion, sudomotor dysfunction remains underexplored.

Method: As part of an ongoing natural history study, consecutive patients diagnosed with PAF were systematically phenotyped and followed longitudinally until phenoconversion or death. Sudomotor function was assessed using thermoregulatory sweat testing (TST) and dynamic sweat testing (DST). Combined results were used to localize sudomotor dysfunction as preganglionic, postganglionic, or mixed.

Results: 69 PAF patients underwent sudomotor testing: 40/69 (58%) completed TST and 45/69 (65%) completed DST. On TST, 29/40 (73%) demonstrated global anhidrosis, 8/40 (20%) length-dependent sweat loss, 2/40 (5%) regional anhidrosis, and 1/40 (2%) unilateral anhidrosis. Among those with global anhidrosis, 22/29 (76%) remained PAF, 3/29 (10%) developed DLB, and 4/29 (14%) developed MSA. Patients without global anhidrosis either remained PAF or phenoconverted to PD/DLB. DST showed reduced sweating in 43/45 patients (95.5%) and a predominantly length dependent distribution in patients with stable PAF compared with MSA, with no difference in the rate of sweat output decline over time.

Conclusion: Global anhidrosis is the most common sudomotor pattern in MSA and is associated with a non–length-dependent impairment of postganglionic sudomotor fibres. In contrast, a length-dependent sudomotor deficit is more suggestive of a restricted postganglionic alpha-synucleinopathy, such as PAF.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pattern-and-progression-of-sudomotor-dysfunction-in-alpha-synucleinopathies/