Quantitative sensory testing and norepinephrine levels in REM sleep behaviour disorder – a clue to early peripheral autonomic and sensory dysfunction?

Journal of Neurology, vol. 269, pp. 923–932

Abstract

INTRODUCTION: Studies have reported autonomic impairment in patients with idiopathic REM sleep behaviour disorder (iRBD), which is considered a prodromal stage of alpha-synucleinopathies. It is still debated whether central or peripheral pathologies are first manifestations of alpha-synucleinopathies. This study aimed to characterize autonomic and somatosensory function in iRBD patients. METHODS: This cross-sectional prospective case-control study included 17 iRBD patients (mean age 66.3 ± 9.2 years) and 16 healthy controls (HCs, 66.6 ± 11.3 years). Quantitative sensory testing, neurological and neuropsychological assessments, norepinephrine blood plasma levels, tilt table examination with orthostatic blood pressure, and heart rate variability were carried out. Longitudinal data of 10 iRBD patients, including neurological, neuropsychological, and tilt table examination, were assessed. RESULTS: iRBD patients more frequently presented with orthostatic dysfunction than HCs (70.6% vs. 6.3%, p < 0.0001). Supine norepinephrine plasma levels were normal, but lower in iRBD (249.59 ± 99.78 pg/ml iRBD, 354.13 ± 116.38 pg/ml HCs, p < 0.05). Quantitative sensory testing revealed impaired cold (CDT) and vibration detection thresholds (VDT) on the foot in iRBD (CDT foot iRBD - 1.24 ± 0.31, HCs - 9.89E-17 ± 0.25, VDT iRBD - 1.11 ± 0.47, HCs - 1.46E-16 ± 0.25, p < 0.05). Cold detection thresholds differed between the foot and hand among iRBD patients (foot - 1.24 ± 0.31, hand - 0.56 ± 0.25, p < 0.05). Longitudinal data revealed an increase in maximum systolic and diastolic orthostatic blood pressure changes and a decrease in the Valsalva ratio in the follow-up group (p < 0.05). CONCLUSION: This study revealed autonomic dysfunction with somatosensory impairment, and decreased norepinephrine levels in iRBD, which may serve as a possible prodromal marker for developing alpha-synucleinopathy.

Authors 8

1. Julia Koch Aachen Department of Neurology, Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Department of Neurology, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany

2. Kira Willemsen Aachen Department of Neurology, Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Department of Neurology, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany

3. Imis Dogan Aachen Department of Neurology, Medical Faculty JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11) Medical Faculty

   Forschungszentrum Jülich · Jülich Aachen Research Alliance · RWTH Aachen University

   Affiliation as printed

   Department of Neurology, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany

   JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany

4. Roman Rolke Aachen Department of Palliative Medicine Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Department of Palliative Medicine, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany

5. Jörg Bernhard Schulz Aachen Department of Neurology, Medical Faculty JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11) Medical Faculty

   Forschungszentrum Jülich · Jülich Aachen Research Alliance · RWTH Aachen University

   Affiliation as printed

   Department of Neurology, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany

   JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany

6. Johannes Schiefer Aachen Department of Neurology, Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Department of Neurology, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany

7. Kathrin Reetz Aachen Department of Neurology, Medical Faculty JARA Brain Institute Molecular Neuroscience and Neuroimaging (INM-11) Medical Faculty

   Forschungszentrum Jülich · Jülich Aachen Research Alliance · RWTH Aachen University

   Affiliation as printed

   Department of Neurology, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany

   JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany

8. Andrea Maier corresponding Aachen Department of Neurology, Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Department of Neurology, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany. amaier@ukaachen.de

   Department of Neurology, Medical Faculty RWTH Aachen University, Pauwelsstraße 30, D-52074, Aachen, Germany