Cardiovascular autonomic failure correlates with cutaneous autonomic denervation in PD and MSA

Purpose: Cardiovascular autonomic failure and neurogenic orthostatic hypotension (nOH) are common and disabling in Parkinson’s disease (PD) and multiple system atrophy (MSA). Recent studies have shown evidence of postganglionic autonomic denervation in MSA as well as PD. We aimed to characterise the relationship between nOH, autonomic failure and postganglionic denervation in PD and MSA. We hypothesised that postganglionic autonomic denervation contributes to the development of nOH and correlates with the severity of cardiovascular autonomic failure. Methods: We assessed 57 patients (37 PD, 20 MSA, median 64 [IQR 59–70] years) with cardiovascular autonomic testing; dynamic sweat testing; plasma noradrenaline levels; skin biopsies for quantification of intraepidermal, pilomotor and sudomotor innervation; and autonomic symptom questionnaires. Results: Overall, 78% of patients with MSA and 36% with PD had nOH ≥ 20/10 mmHg. The MSA group had more severe nOH, sudomotor dysfunction and cutaneous denervation, with higher supine noradrenaline than the PD group. Only supine noradrenaline differed between MSA and PD with nOH subgroups (P = 0.04). Overall, patients with nOH demonstrated more severe (1) cardiovascular autonomic failure, with reduced pressor responses to isometric exercise, deep breathing and Valsalva ratio; (2) intraepidermal, pilomotor and sudomotor denervation; and (3) autonomic symptoms and Hoehn–Yahr grade. The severity of nOH and cardiovascular autonomic failure correlated with autonomic denervation, patient symptoms and Hoehn–Yahr grade (ρ ≥ 0.50). Conclusions: nOH was associated with cutaneous autonomic denervation in both PD and MSA, with correlations between cardiovascular autonomic failure, cutaneous denervation and Hoehn–Yahr grade. Postganglionic autonomic denervation may contribute to nOH in PD and MSA, and affect responses to therapeutic agents.