Multicenter Study

. 2023 Dec 12;101(24):e2545-e2559.

doi: 10.1212/WNL.0000000000207883. Epub 2023 Oct 19.

Frequency of Orthostatic Hypotension in Isolated REM Sleep Behavior Disorder

Jonathan E Elliott¹, Mohini D Bryant-Ekstrand¹, Allison T Keil¹, Brittany R Ligman¹, Miranda M Lim¹, Jennifer Zitser¹, Emmanuel H During¹, Jean-Francois Gagnon¹, Erik K St Louis¹, Julie A Fields¹, Daniel E Huddleston¹, Donald L Bliwise¹, Alon Y Avidan¹, Carlos H Schenck¹, Jennifer McLeland¹, Susan R Criswell¹, Albert A Davis¹, Aleksandar Videnovic¹, Joyce K Lee-Iannotti¹, Ronald Postuma¹, Bradley F Boeve¹, Yo-El S Ju¹, Mitchell G Miglis¹; for North American Prodromal Synucleinopathy (NAPS) Consortium¹

Collaborators, Affiliations

Collaborators

for North American Prodromal Synucleinopathy (NAPS) Consortium:
Klemens Angstwurm, Antonios Bayas, Achim Berthele, Judith Bellmann-Strobl, Felix Bischof, Stefan Bittner, Tobias Böttcher, Johannes Brettschneider, Marcus DSouza, Barbara Ettrich, Jürgen Faiss, Benedikt Frank, Anna Gahlen, Achim Gass, Matthias Grothe, Kerstin Guthke, Eva Marie Habedank, Bernhard Hemer, Frank Hoffman, Olaf Hoffan, Ulrich Hofstadt-van Oy, Jutta Junghans, Barbara Kaulen, Peter Kern, Christoph Kleinschnitz, Wolfgang Köhler, Melanie Korsen, Markus Kowarik, Markus Krumbholz, Stefan Langel, Klaudia Lepka, Martin Liebetrau, Ralf Linker, De-Hyung Lee, Felix Luessi, Martin Marziniak, Christoph Mayer, Stefanie Meister, Arthur Melms, Imke Metz, Christoph Münch, Oliver Neuhaus, Sabine Niehaus, Florence Pache, Marc Pawlitzki, Hans-Ulrich Puhlmann, Refik Pul, Kevin Rostásy, Lioba Rückriem, Klemens Ruprecht, Christoph Ruschil, Sven Schippling, Simon Schuster, Matthias Schwab, Makbule Senel, Jörn Peter Sieb, Nadja Siebert, Claudia Sommer, Annette Spreer, Martin Stangel, Andrea Steinbrecher, Heike Stephanik, Muriel Stoppe, Marie Süße, Björn Tackenberg, Florian Then-Bergh, Johannes Tünnerhoff, Annette Walter, Klaus-Peter Wandinger, Clemens Warnke, Martin Weber, Robert Weissert, Heinz Wiendl, Christian Wilke, Alexander Winkelmann, Yavor Yalachkov, Lena Zeltner, Christian Zentner, Ulf Ziemann, Frauke Zipp

Affiliation

¹ Department of Neurology (J.E.E., M.M.L.), Oregon Health & Science University; Research Service (J.E.E., M.D.B.-E., A.T.K., B.R.L.), Mental Illness Research Education and Clinical Center (M.M.L.), Department of Neurology (M.M.L.), and National Center for Rehabilitative Auditory Research (M.M.L.), VA Portland Health Care System; Department of Behavioral Neuroscience (M.M.L.), Oregon Health & Science University; Oregon Institute of Occupational Health Sciences (M.M.L.), Oregon Health & Science University, Portland; Tel Aviv Sourasky Medical Center (J.Z.), Israel; Department of Psychiatry and Behavioral Sciences (E.H.D., M.G.M.), Stanford University Medical Center, Redwood City; Department of Neurology & Neurological Sciences (E.H.D., M.G.M.), Stanford University, Palo Alto, CA; Department of Psychology (J.-F.G., R.P.), Université du Québec à Montréal; Center for Advanced Research in Sleep Medicine (J.-F.G.), Hôpital du Sacré-Coeur de Montréal, Quebec, Canada; Mayo Clinic College of Medicine and Science (E.K.S.L., J.A.F., B.F.B.), Rochester, MN; Department of Neurology (D.E.H., D.L.B.), Emory University, Atlanta, GA; Sleep Medicine Program (A.Y.A.), Department of Neurology, David Geffen School of Medicine, University of California Los Angeles; Department of Psychiatry (C.H.S.), University of Minnesota Medical School, Minneapolis; Department of Neurology (J.M., S.R.C., A.A.D., Y.-E.S.J.), Washington University School of Medicine, St. Louis, MO; Movement Disorders Unit (A.V.), Division of Sleep Medicine, Massachusetts General Hospital; Neurological Clinical Research Institute (A.V.), Harvard Medical School, Boston, MA; Department of Neurology (J.K.L.-I.), Banner University Medical Center, Phoenix, AZ; Banner Sun Health Research Institute (J.K.L.-I.), Sun City, AZ; and Montréal Neurologique Institute (R.P.), McGill Université, Québec, Canada.

PMID: 37857496
PMCID: PMC10791057
DOI: 10.1212/WNL.0000000000207883

Multicenter Study

Frequency of Orthostatic Hypotension in Isolated REM Sleep Behavior Disorder

Jonathan E Elliott et al. Neurology. 2023.

. 2023 Dec 12;101(24):e2545-e2559.

doi: 10.1212/WNL.0000000000207883. Epub 2023 Oct 19.

Authors

Collaborators

for North American Prodromal Synucleinopathy (NAPS) Consortium:
Klemens Angstwurm, Antonios Bayas, Achim Berthele, Judith Bellmann-Strobl, Felix Bischof, Stefan Bittner, Tobias Böttcher, Johannes Brettschneider, Marcus DSouza, Barbara Ettrich, Jürgen Faiss, Benedikt Frank, Anna Gahlen, Achim Gass, Matthias Grothe, Kerstin Guthke, Eva Marie Habedank, Bernhard Hemer, Frank Hoffman, Olaf Hoffan, Ulrich Hofstadt-van Oy, Jutta Junghans, Barbara Kaulen, Peter Kern, Christoph Kleinschnitz, Wolfgang Köhler, Melanie Korsen, Markus Kowarik, Markus Krumbholz, Stefan Langel, Klaudia Lepka, Martin Liebetrau, Ralf Linker, De-Hyung Lee, Felix Luessi, Martin Marziniak, Christoph Mayer, Stefanie Meister, Arthur Melms, Imke Metz, Christoph Münch, Oliver Neuhaus, Sabine Niehaus, Florence Pache, Marc Pawlitzki, Hans-Ulrich Puhlmann, Refik Pul, Kevin Rostásy, Lioba Rückriem, Klemens Ruprecht, Christoph Ruschil, Sven Schippling, Simon Schuster, Matthias Schwab, Makbule Senel, Jörn Peter Sieb, Nadja Siebert, Claudia Sommer, Annette Spreer, Martin Stangel, Andrea Steinbrecher, Heike Stephanik, Muriel Stoppe, Marie Süße, Björn Tackenberg, Florian Then-Bergh, Johannes Tünnerhoff, Annette Walter, Klaus-Peter Wandinger, Clemens Warnke, Martin Weber, Robert Weissert, Heinz Wiendl, Christian Wilke, Alexander Winkelmann, Yavor Yalachkov, Lena Zeltner, Christian Zentner, Ulf Ziemann, Frauke Zipp

Affiliation

¹ Department of Neurology (J.E.E., M.M.L.), Oregon Health & Science University; Research Service (J.E.E., M.D.B.-E., A.T.K., B.R.L.), Mental Illness Research Education and Clinical Center (M.M.L.), Department of Neurology (M.M.L.), and National Center for Rehabilitative Auditory Research (M.M.L.), VA Portland Health Care System; Department of Behavioral Neuroscience (M.M.L.), Oregon Health & Science University; Oregon Institute of Occupational Health Sciences (M.M.L.), Oregon Health & Science University, Portland; Tel Aviv Sourasky Medical Center (J.Z.), Israel; Department of Psychiatry and Behavioral Sciences (E.H.D., M.G.M.), Stanford University Medical Center, Redwood City; Department of Neurology & Neurological Sciences (E.H.D., M.G.M.), Stanford University, Palo Alto, CA; Department of Psychology (J.-F.G., R.P.), Université du Québec à Montréal; Center for Advanced Research in Sleep Medicine (J.-F.G.), Hôpital du Sacré-Coeur de Montréal, Quebec, Canada; Mayo Clinic College of Medicine and Science (E.K.S.L., J.A.F., B.F.B.), Rochester, MN; Department of Neurology (D.E.H., D.L.B.), Emory University, Atlanta, GA; Sleep Medicine Program (A.Y.A.), Department of Neurology, David Geffen School of Medicine, University of California Los Angeles; Department of Psychiatry (C.H.S.), University of Minnesota Medical School, Minneapolis; Department of Neurology (J.M., S.R.C., A.A.D., Y.-E.S.J.), Washington University School of Medicine, St. Louis, MO; Movement Disorders Unit (A.V.), Division of Sleep Medicine, Massachusetts General Hospital; Neurological Clinical Research Institute (A.V.), Harvard Medical School, Boston, MA; Department of Neurology (J.K.L.-I.), Banner University Medical Center, Phoenix, AZ; Banner Sun Health Research Institute (J.K.L.-I.), Sun City, AZ; and Montréal Neurologique Institute (R.P.), McGill Université, Québec, Canada.

PMID: 37857496
PMCID: PMC10791057
DOI: 10.1212/WNL.0000000000207883

Abstract

Background and objectives: Although orthostatic hypotension (OH) can be an early feature of autonomic dysfunction in isolated REM sleep behavior disorder (iRBD), no large-scale studies have examined the frequency of OH in iRBD. In this study, we prospectively evaluated the frequency of OH in a large multicenter iRBD cohort.

Methods: Participants 18 years or older with video polysomnogram-confirmed iRBD were enrolled through the North American Prodromal Synucleinopathy consortium. All participants underwent 3-minute orthostatic stand testing to assess the frequency of OH, and a Δ heart rate/Δ systolic blood pressure (ΔHR/ΔSBP) ratio <0.5 was used to define reduced HR augmentation, suggestive of neurogenic OH. All participants completed a battery of assessments, including the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction (SCOPA-AUT) and others assessing cognitive, motor, psychiatric, and sensory domains.

Results: Of 340 iRBD participants (65 ± 10 years, 82% male), 93 (27%) met criteria for OH (ΔHR/ΔSBP 0.37 ± 0.28; range 0.0-1.57), and of these, 72 (77%) met criteria for OH with reduced HR augmentation (ΔHR/ΔSBP 0.28 ± 0.21; range 0.0-0.5). Supine hypertension (sHTN) was present in 72% of those with OH. Compared with iRBD participants without OH, those with OH were older, reported older age of RBD symptom onset, and had worse olfaction. There was no difference in autonomic symptom scores as measured by SCOPA-AUT.

Discussion: OH and sHTN are common in iRBD. However, as patients may have reduced autonomic symptom awareness, orthostatic stand testing should be considered in clinical evaluations. Longitudinal studies are needed to clarify the relationship between OH and phenoconversion risk in iRBD.

Trial registration information: ClinicalTrials.gov: NCT03623672; North American Prodromal Synucleinopathy Consortium.

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Conflict of interest statement

J.E. Elliott has received support from the Department of Veteran Affairs, NIH (NHLBI, NIA, NCCIH), Oregon Medical Research Foundation, Portland VA Research Foundation, Eugene & Clarissa Evonuk Foundation in Environmental Physiology, and American Heart Association. M.D. Bryant-Ekstrand, A.T. Keil, and B.R. Ligman have no disclosures. M.M. Lim has received support from federal, state, and nonprofit organizations including: Department of Veteran Affairs, Department of Defense, NIH (NIMH, NHLBI, NIA, NCCIH, NINDS, NIGMS, NCATS), NSF, Military Traumatic Brain Injury Initiative (Henry Jackson Foundation), Oregon Medical Research Foundation, Collins Medical Trust, Brain & Behavior Foundation (NARSAD), American Sleep Medicine Foundation, Hartford Center of Gerontological Excellence, Pacific Northwest National Laboratory, and Portland VA Research Foundation. M.M. Lim receives compensation as a member of the Scientific Advisory Board for Applied Cognition. J. Zitser has no disclosures. E.H. During has received support from Jazz Pharmaceuticals, Sanofi, Takeda, Rythm Inc., and the Feldman Foundation CA. R.B. Postuma has received support from the Fonds de Recherche du Quebec–Santé, the Canadian Institutes of Health Research, the Parkinson Society of Canada, the Weston-Garfield Foundation, the Michael J. Fox Foundation, the Webster Foundation; and personal fees from Takeda, Roche/Prothena, Teva Neurosciences, Novartis Canada, Biogen, Boehringer Ingelheim, Ther-anexus, GE HealthCare, Jazz Pharmaceuticals, Abbvie, Jannsen, Otsuko, Phytopharmics, Inception Sciences, and Curasen. A.A. Davis has received research support from the Department of Defense, NIH (NINDS), and the Michael J. Fox Foundation. J.-F. Gagnon has received support from the NIH, the Canadian Institutes of Health Research and the Fonds de Recherche du Québec–Santé. E.K. St. Louis has received support from NIH (NIA, NINDS, and NHLBI), the Michael J. Fox Foundation, Harmony, Inc., and Sunovion, Inc. J.A. Fields has received support from the NIH and is a consultant for Medtronic, Inc. D.L. Bliwise has received support from the NIH and has been a Consultant to CliniLabs, Eisai, Ferring, Huxley, Idorsia, and Merck. D.E. Huddleston has received support from NIH (NIA, NINDS, Department of Veteran Affairs), the American Parkinson's Disease Association Center for Advanced Research, the Emory Udall Parkinson's Disease Research Center, the Emory Lewy Body Dementia Association Research Center of Excellence, the Emory Alzheimer's Disease Research Center, the Michael J Fox Foundation, the Georgia Research Alliance, the Bumpus Family Foundation, and the McMahon Family. A.Y. Avidan has received consultant fees from Avadel, Merck, Takeda, Eisai, Idorsia and Harmony, and speaker honoraria from Merck, Eisai, Harmony and Idorsia. C.H. Schenck has received a one-time speaker honorarium from Eisai, Inc. J. McLeland has no disclosures. S.R. Criswell has received support from the NIH and consulting fees from Abbvie and Sio Gene Therapies. A. Videnovic has received research support from the NIH and the Michael J Fox Foundation; consultancy fees from Alexion Pharmaceuticals, Biogen, XW Pharma, Jazz. J.K. Lee-Iannotti has received support from NIH, Liva Nova, Respicardia, and the Arizona Alzheimer's Consortium. She serves on the Scientific Advisory Board for Jazz Pharmaceuticals, INSPIRE, and Avadel. She is a consultant and speaker for Jazz Pharmaceuticals. B.F. Boeve has served as an investigator for clinical trials sponsored by Alector, Biogen and Transposon. He serves on the Scientific Advisory Board of the Tau Consortium, which is funded by the Rainwater Charitable Foundation. He receives support from NIH, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, the Little Family Foundation, and the Ted Turner and Family Foundation. Y.E. Ju has received support from the NIH and the Centene Corporation contract (P19-00559) for the Washington University-Centene ARCH Personalized Medicine Initiative; and compensation for consultant activities for Applied Cognition. M.G. Miglis has received support from Jazz Pharmaceuticals, Embr Wave, and Biohaven Pharmaceuticals; Consulting fees from 2nd MD, Infinite MD and Guidepoint LLC; Payments for CME lectures from MED-IQ; and Royalties from Elsevier Inc. Go to Neurology.org/N for full disclosures.

Figures

**Figure 1. Systolic and Diastolic Blood Pressure**
Systolic (A) and diastolic (B) BPs as well as heart rate (C) when supine and after standing between the normal BP group (open violin plot), OH (light shaded violin plot), and OH-HR augmentation (heavy shaded violin plot). Individual data points and connecting supine vs standing outcomes are plotted. The center line for each violin plot represents the mean with 75% and 25% quartiles above and below, respectively. Each plot is unsmoothed extended from min to max, reflecting an overall cohort distribution. *p < 0.05. BP = blood pressure; HR = heart rate; OH = orthostatic hypotension.

**Figure 2. Change in SBP/DBP and HR**
Changes in SBD (A), DBP (B), HR (C), and the ΔHR/ΔSBP ratio (D) are presented. The open, light-shaded and heavy-shaded bars reflect the mean value for the normal BP group, OH, and OH-HR augmentation participants, respectively, with standard deviation error bars extending above/below. All individual data points are presented for transparency. *p < 0.05. BP = blood pressure; DBP = diastolic blood pressure; HR = heart rate; OH = orthostatic hypotension; SBP = systolic blood pressure.

**Figure 3. SCOPA-AUT Total Score and Subscales**
The overall SCOPA-AUT total score and each of 7 subscales were normalized to the total possible score and presented as a % impairment within each category (i.e., total score, gastrointestinal, bowel, urinary, cardiovascular, thermoregulatory, visual, and sexual function). SCOPA-AUT total score = 59, with subscales ranging from 1 to 5 questions (scores of 3–15). The open, light-shaded and heavy-shaded bars reflect the mean value for the normal BP group, OH, and OH-HR augmentation participants, respectively. *p < 0.05. BP = blood pressure; HR = heart rate; OH = orthostatic hypotension; SCOPA-AUT = Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction.

See this image and copyright information in PMC

References

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Frequency of Orthostatic Hypotension in Isolated REM Sleep Behavior Disorder

Collaborators

Affiliation

Frequency of Orthostatic Hypotension in Isolated REM Sleep Behavior Disorder

Authors

Collaborators

Affiliation

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources