Abstract
ObjectiveWith a combination of different sympathetic tests, we aimed to elucidate whether impairment of sympathetic function in Parkinson's disease (PD) is the consequence of a central or peripheral efferent dysfunction.MethodsThirty‐five patients with early‐to‐intermediate PD (median age: 63 years; IQR: 57–67 years; disease duration 1–9 years, 15 women) and 20 age‐ and sex‐matched healthy controls (median age: 64.5 years; IQR: 58–68 years; 10 women) were recruited. Autonomic testing was performed in two subgroups and included the assessment of resting cardiovascular parameters, postprandial hypotension (PPH), orthostatic hypotension (OH), and vasoconstriction induced by intradermal microdialysis with different concentrations of norepinephrine (NE; 10–5; 10–6; 10–7; 10–8) and by cold through forehead cooling. We also used sympathetic multiunit microneurography (muscle sympathetic nerve activity; MSNA; burst frequency (BF): bursts per minute; burst incidence (BI): bursts per 100 heart beats) and evaluated the presence of phosphorylated α‐synuclein deposits in skin innervation in biopsies from the thighs by immunohistohemistry.ResultsDiastolic blood pressure was higher in the PD group at rest (p < .001) and during OH (F = 6.533; p = .022). Vasoconstriction induced by NE microdialysis and cold was unchanged in PD patients. MSNA was lower in PD patients than in controls (BF: p = .001; BI: p = .025). Phosphorylated α‐synuclein deposits could be found only in PD patients.ConclusionWe did not find indications for peripheral sympathetic nerve fiber dysfunction or adrenoreceptor sensitivity changes. The decreased MSNA argues in favor of central sympathetic impairment.
Highlights
In Parkinson's disease (PD), autonomic disturbances sometimes pre‐ cede the typical motor triad, indicate progress with disease duration (Guo et al, 2013) and have been proposed as predictive markers (Palma & Kaufmann, 2014)
We aimed to explore whether early‐to‐intermediate PD patients have an impairment of autonomic function, and if so, whether it would be due to peripheral mechanisms such as sympathetic nerve fiber degeneration and altered adrenoreceptor responsiveness, or whether such impairment rather would reflect central sympathetic disturbance
Patient group 2:15 patients suffering from early‐to‐intermediate stage idiopathic PD (median age: 62 years (IQR: 57.0–65 years); 6 women; Hoehn and Yahr (H&Y) 1: n = 6; H&Y 2: n = 7 H&Y 3: n = 2; URPDS III: me‐ dian: 7.0 (IQR: 3.8–16.0); disease duration: median 3 years (IQR: 2–5 years)); 10 age‐ and sex‐matched healthy controls (median age: 58 years (IQR 57–61.25 years); 6 women) underwent the following investigations: (a) resting blood pressure and heart rate; (b) testing of orthostatic hypotension; (c) skin biopsy; and (d) assessment of mus‐ cle sympathetic nerve activity (MSNA)
Summary
| 2 of 10 in particular orthostatic intolerance and postprandial hypotension (Sharabi, Imrich, Holmes, Pechnik, & Goldstein, 2008). The presence of these deposits is associated with a reduction of synaptic proteins, progressive deficiency in neuronal connectivity as well as excitabil‐ ity and neuronal death (Volpicelli‐Daley et al, 2011) Their potential clinical relevance for sympathetic denervation is indicated by their abundance in patients with pure autonomic failure (Donadio et al, 2013). It was only recently shown that in PD with orthostatic hypotension (OH) higher levels of P‐α‐synuclein deposits can be de‐ tected in autonomic nerve fibers in the skin compared to PD patients without OH (Donadio et al, 2018) It remained unclear whether these α‐synuclein deposits are associated with further clin‐ ically relevant autonomic deficits in PD.
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