Dysautonomia in prodromal α-synucleinopathy: peripheral versus central autonomic degeneration
C. Dahms
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorA. Guenther
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorM. Schwab
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorT. Schultze
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorS. Nowack
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorD. Hoyer
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorJ. Ehrhardt
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorO. W. Witte
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorCorresponding Author
S. Rupprecht
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Correspondence: S. Rupprecht, Hans Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, D-07740 Jena, Germany (tel.: +49 3641 939 6679; fax: +49 3641 932 3402; e-mail: [email protected]).Search for more papers by this authorC. Dahms
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorA. Guenther
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorM. Schwab
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorT. Schultze
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorS. Nowack
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorD. Hoyer
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorJ. Ehrhardt
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorO. W. Witte
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Search for more papers by this authorCorresponding Author
S. Rupprecht
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany
Correspondence: S. Rupprecht, Hans Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, D-07740 Jena, Germany (tel.: +49 3641 939 6679; fax: +49 3641 932 3402; e-mail: [email protected]).Search for more papers by this authorAbstract
Background and purpose
There is an urgent need for early predictive markers for the course of disease in prodromal α-synucleinopathies such as idiopathic rapid eye movement (REM) sleep behaviour disorder. Autonomic cardiac/vascular dysfunction is a prominent feature in advanced α-synucleinopathies, but its diagnostic value as an early neurodegenerative marker remains unclear. The latter may be complicated since synuclein-mediated neurodegeneration may involve central and peripheral components of the autonomic nervous system.
Methods
The diagnostic value of autonomic symptoms and central and peripheral autonomic markers of blood pressure and heart rate regulation were prospectively evaluated in 20 subjects with idiopathic REM sleep behaviour disorder and 20 age-matched healthy controls.
Results
Although subjects with REM sleep behaviour disorder showed no clinical autonomic symptoms, blood pressure (P ≤ 0.035) and heart rate response (P ≤ 0.065) were slightly diminished during orthostatic challenge. Autonomic dysregulation was distinctively reflected in lower resting heart rate (all components, P ≤ 0.05) and blood pressure variability (low frequency component, P ≤ 0.024) indicating peripheral cardiac/vascular denervation. In contrast, baroreflex sensitivity and central cardiac autonomic outflow (sympathovagal balance) were well preserved indicating intact central autonomic regulation. Heart rate variability [very low frequency component, receiver operating characteristic (ROC) area under the curve (AUC) 0.80, P ≤ 0.001] and blood pressure variability (low frequency component ROC AUC 0.73, P ≤ 0.01) but not baroreflex sensitivity and sympathovagal balance showed an excellent diagnostic accuracy in identifying subjects with REM sleep behaviour disorder and healthy controls.
Conclusions
Cardiac/vascular dysfunction in prodromal α-synucleinopathy arises from peripheral rather than from central autonomic degeneration. Autonomic indices encoded in heart rate and blood pressure variability are precise functional markers of early synuclein-mediated neurodegeneration.
Supporting Information
| Filename | Description |
|---|---|
| ene12957-sup-0001-TableS1.docxWord document, 24.6 KB | Table S1. Baseline characteristics of subjects with and without substantia nigra hyperechogenicity (patients with iRBD and healthy controls). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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