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. 2019 Dec;9(12):e01463.
doi: 10.1002/brb3.1463. Epub 2019 Nov 5.

Reduced central sympathetic activity in Parkinson's disease

Heidrun H Krämer  1 , Gothje Lautenschläger  1 , Michael de Azevedo  1 , Kathrin Doppler  2 , Anne Schänzer  3 , Christoph Best  4 , Wolfgang H Oertel  4 , Iris Reuter  1 , Claudia Sommer  2 , Frank Birklein  5
Affiliations

Reduced central sympathetic activity in Parkinson's disease

Heidrun H Krämer et al. Brain Behav. 2019 Dec.

Abstract

Objective: With 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.

Methods: Thirty-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.

Results: Diastolic 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.

Conclusion: We did not find indications for peripheral sympathetic nerve fiber dysfunction or adrenoreceptor sensitivity changes. The decreased MSNA argues in favor of central sympathetic impairment.

Keywords: MSNA; Parkinson's disease; autonomic failure; phosphorylated α-synuclein deposits.

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Conflict of interest statement

The authors have no conflict of interest to report.

Figures

Figure 1
Figure 1
Represents the time course analysis of the degree of vasoconstriction induced by the applied NE concentrations (a: NE 10–5; b: NE 10–6; c: NE 10–7; d: NE 10–8) in healthy controls (open triangles) and PD patients (filled squares). The degree of vasoconstriction is represented in flux intensity normalized to baseline in arbitrary perfusion units. The extent of the vasoconstriction did not differ between PD patients and healthy participants (ns; rm‐ANOVA)
Figure 2
Figure 2
Shows the cold induced acral vasoconstriction over time during forehead cooling in healthy controls (open triangles) and PD patients (filled squares). No differences could be detected between the groups (ns, rm‐ANOVA)
Figure 3
Figure 3
Depicts the diastolic blood pressure (DBP) (a) and the systolic blood pressure (SBP) over time (b) in mmHg during the orthostatic hypotension test. DBP is higher in PD patients (filled squares) compared to healthy controls (open triangles; F = 6.533; p = .022; rm‐ANOVA). SBP did not differ between PD patients and healthy controls (ns)
Figure 4
Figure 4
Photomicrograph of a double‐immunofluorescence staining with anti‐α‐synuclein (a, c) and anti‐PGP9.5 (b and c) in a biopsy of a patient with PD. P‐α‐synuclein is detectable within a dermal nerve fiber (c). Bar = 20 µm
See this image and copyright information in PMC

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