Two‐Year observational study of autonomic skin function in patients with Parkinson's disease compared to healthy individuals

Background and purpose We characterized autonomic pilomotor and sudomotor skin function in early Parkinson's disease (PD) longitudinally. Methods We enrolled PD patients (Hoehn and Yahr 1–2) and healthy controls from movement disorder centers in Germany, Hungary, and the United States. We evaluated axon‐reflex responses in adrenergic sympathetic pilomotor nerves and in cholinergic sudomotor nerves and assessed sympathetic skin response (SSR), predominantly parasympathetic neurocardiac function via heart rate variability, and disease‐related symptoms at baseline, after 2 weeks, and after 1 and 2 years. Clinicaltrials.gov : NCT03043768. Results We included 38 participants: 26 PD (60% females, aged 62.4 ± 7.4 years, mean ± SD) and 12 controls (75% females, aged 59.5 ± 5.8 years). Pilomotor function was reduced in PD compared to controls at baseline when quantified via spatial axon‐reflex spread (78 [43–143], median [interquartile range] mm 2 vs. 175 [68–200] mm 2 , p = 0.01) or erect hair follicle count in the axon‐reflex region (8 [6–10] vs. 11 [6–16], p = 0.008) and showed reliability absent any changes from baseline to Week 2 ( p = not significant [ns]). Between‐group differences increased over the course of 2 years ( p < 0.05), although no decline was observed within groups ( p = ns). Pilomotor impairment in PD correlated with motor symptoms (rho = −0.59, p = 0.017) and was not lateralized ( p = ns). Sudomotor axon‐reflex and neurocardiac function did not differ between groups ( p = ns), but SSR was reduced in PD ( p = 0.0001). Conclusions Impairment of adrenergic sympathetic pilomotor function and SSR in evolving PD is not paralleled by changes to cholinergic sudomotor function and parasympathetic neurocardiac function, suggesting a sympathetic pathophysiology. A pilomotor axon‐reflex test might be useful to monitor PD‐related pathology.