Abstract Details

Title Cutaneous Phosphorylated Alpha-synuclein Deposition in Pure Autonomic Failure

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-002

Objective The Synuclein-One study is an NIH-funded 30-site trial that included 33 participants with pure autonomic failure (PAF). We report the detection and quantitation of cutaneous phosphorylated alpha-synuclein (P-SYN) in patients with suspected PAF.

Background PAF is a peripheral neurodegenerative disease associated with the deposition of P-SYN. The differential diagnoses include peripheral autonomic neuropathies, ganglionopathies and other neurodegenerative diseases. Up to 10% of patients per year phenocovert to a central synucleinopathy. No diagnostic test exists to confirm the underlying pathology, to predict phenoconversion risk or the central synucleinopathy subtype.

Design/Methods After consent, participants with PAF (or healthy controls) completed neurologic examinations, medical history review, cognitive evaluation, orthostatic vital signs and neurodegenerative disease questionnaires. All participants underwent blinded review by a panel of experts to confirm a diagnosis of PAF. Skin biopsies at the distal leg, distal thigh and posterior cervical sites were performed on all participants with quantitation of P-SYN.

Results 120 controls and 33 PAF participants were enrolled. The expert panel excluded 11 patients with PAF (8 phenoconverted to another synucleinopathy and 3 with peripheral autonomic neuropathy). Of the 22 with confirmed PAF, P-SYN was detected in 22/22 (100%) and in 8/8 (100%) of those who had phenoconverted to another synucleinopathy. Of the 3 with suspected peripheral autonomic neuropathy, 3/3 (100%) had peripheral neuropathy on skin biopsy, but 2/3 (66%) also had evidence of P-SYN on skin biopsy. Of the 120 controls, P-SYN was detected in 4/120 (3.7%).

Conclusions Cutaneous P-SYN testing is sensitive and specific for detection of P-SYN in patients with suspected PAF. The presence of misfolded synuclein should be considered in the differential diagnosis of peripheral autonomic neuropathies. Phenoconversion to another synucleinopathy was noted in 25% of enrolled subjects. Longitudinal studies with serial skin biopsies and topographic analysis may offer insight into phenoconversion risk and synucleinopathy subtype.

Authors/Disclosures
Roy L. Freeman, MD (Beth Israel Deaconess Hosp) PRESENTER	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.
Todd D. Levine, MD (Honor Health)	Dr. Levine has received personal compensation for serving as an employee of CND life sciences . Dr. Levine has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Nufactor. Dr. Levine has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for PNA. Dr. Levine has or had stock in CND Life Sciences.Dr. Levine has or had stock in Corinthian reference lab.
Bailey Bellaire (CND Life Sciences)	Bailey Bellaire has received personal compensation for serving as an employee of CND Life Sciences.
Jade Stohl (CND Life Sciences)	No disclosure on file
Christopher H. Gibbons, MD, FAAN (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.

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