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Abstract Details

Cutaneous Alpha-Synuclein is Correlated with Autonomic Impairment in Isolated REM Sleep Behavior Disorder
Sleep
S9 - Sleep: Highlight Presentations on RBD (2:32 PM-2:40 PM)
004
To define the deposition of p-syn in iRBD and correlations with markers of autonomic dysfunction.
Phosphorylated α-synuclein (p-syn) has been detected within cutaneous autonomic nerve fibers of patients with central nervous system (CNS) α-synucleinopathies such as Parkinson’s disease (PD), dementia with Lewy bodies, and more recently isolated REM sleep behavior disorder (iRBD). We now report the first US data on the deposition of p-syn in iRBD and its correlation with subjective and objective measures of autonomic dysfunction.
Twenty-five iRBD patients had quantified neurological and cognitive examinations, autonomic function testing, smell testing, questionnaires and punch skin biopsies taken from multiple proximal and distal sites. Skin biopsies were stained for PGP 9.5 and p-syn and results compared to 28 PD patients and 18 healthy controls.

P-syn was detected in in 16/25 (64%) of iRBD patients, compared to 27/28 (96%) of PD and 0/18 controls. The presence of p-syn at any biopsy site was correlated with both sympathetic impairment (CASS adrenergic r = 0.6, p < 0.05) and total autonomic impairment (CASS total r = 0.6, p < 0.05) on autonomic testing. These results were independent of the density of p-syn at each site. There was no correlation between p-syn and antidepressant use.

In patients with iRBD, the presence of p-syn was seen in 64% of cases prior to any other CNS manifestations of neurodegenerative disease.  Those positive for p-syn had evidence of greater autonomic impairment. Longitudinal follow-up is necessary to determine the long-term implications of both cutaneous p-syn and autonomic testing and their use as potential biomarkers in iRBD.
Authors/Disclosures
Mitchell G. Miglis, MD, FÂ鶹´«Ã½Ó³»­ (Stanford University Medical Center)
PRESENTER 		Dr. Miglis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alight Health. Dr. Miglis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint, LLC. Dr. Miglis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for 2nd MD. Dr. Miglis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Jazz Pharmaceuticals. Dr. Miglis has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Van Cott and Talamante. The institution of Dr. Miglis has received research support from Dysautonomia International. The institution of Dr. Miglis has received research support from National Institute of Health. Dr. Miglis has received publishing royalties from a publication relating to health care.
Jennifer Zitser-Koren, MD (UCSF) Dr. Zitser-Koren has nothing to disclose.
Sharika Rajan, MD (NIH) Dr. Rajan has nothing to disclose.
Emmanuel H. During, MD (Stanford) Dr. During has nothing to disclose.
Logan D. Schneider, MD (Stanford/VA Alzheimer's Center) Dr. Schneider has received personal compensation for serving as an employee of Alphabet, Inc. Dr. Schneider has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Jazz Pharmaceuticals. Dr. Schneider has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Avadel Pharmaceuticals. Dr. Schneider has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Axsome. Dr. Schneider has received intellectual property interests from a discovery or technology relating to health care.
Safwan S. Jaradeh, MD, FÂ鶹´«Ã½Ó³»­ (Dept of Neurology) Dr. Jaradeh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Jaradeh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea. Dr. Jaradeh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam & Akcea. The institution of Dr. Jaradeh has received research support from Alnylam.
Roy L. Freeman, MD (Beth Israel Deaconess Hosp) Dr. Freeman has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Cutaneous Diagnostic Life Sciences. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vertex. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Theravance. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Inhibikase. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Freeman has received research support from NIH. The institution of Dr. Freeman has received research support from Theravance. The institution of Dr. Freeman has received research support from Biohaven. The institution of Dr. Freeman has received research support from Lundbeck. Dr. Freeman has received research support from Regeneron.
Christopher H. Gibbons, MD, FÂ鶹´«Ã½Ó³»­ (Beth Israel Deaconess Medical Center) Dr. Gibbons has received personal compensation for serving as an employee of CND Life Sciences. Dr. Gibbons has or had stock in CND Life Sciences.Dr. Gibbons has received publishing royalties from a publication relating to health care.