Abstract
Background
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 denervation in MSA as well as PD.
Objectives
To characterise the relationship between nOH, autonomic failure and markers of postganglionic denervation in PD and MSA.
Methods
We assessed 57 patients (37 PD, 20 MSA, 18 females, median 64[IQR 59-70] years) with autonomic cardiovascular testing, plasma noradrenaline levels, dynamic sweat testing, skin biopsies for quantification of intraepidermal, pilomotor and sudomotor innervation and COMPASS-31 autonomic symptom questionnaires.
Results
78% with MSA and 36% with PD had nOH≥ 20/10mmHg. Overall, compared to patients without nOH, patients with nOH demonstrated greater 1) cardiovascular autonomic failure, with significantly reduced responses to isometric exercise, deep breathing and Valsalva ratio, 2) intraepidermal, pilomotor and sudomotor denervation, 3) autonomic symptoms and Hoehn-Yahr grade. Quantitative cardiovascular biomarkers including nOH severity correlated with autonomic denervation, patient symptoms and Hoehn-Yahr grade (ρ≥0.50).
Compared to PD, MSA patients had worse nOH, pressor responses to isometric exercise, sudomotor dysfunction and cutaneous denervation, with higher supine noradrenaline, but subgroup analysis showed only supine noradrenaline differed significantly between MSA and PD with nOH subgroups (P=.04).
Conclusions
NOH was associated with cutaneous denervation in both PD and MSA, with significant correlations between quantitative cardiovascular autonomic biomarkers, cutaneous denervation, and Hoehn-Yahr grade. Postganglionic denervation may contribute to autonomic failure in PD and MSA and affect responses to therapeutic agents for nOH.