Evidence map›Paper›PMID 34244806›Full record

ArticleSleep2021

Cutaneous α-synuclein is correlated with autonomic impairment in isolated rapid eye movement sleep behavior disorder.

Mitchell G Miglis, Jennifer Zitser, Logan Schneider, Emmanuel During, Safwan Jaradeh, Roy Freeman, Christopher H Gibbons

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Sleep, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07790744 (A Comprehensive, Multimodal Characterization of Prodromal PD in Subjects With RBD), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.6field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07790744 recruitingnot on this mapstarted 2026, after this paper: background citation

A Comprehensive, Multimodal Characterization of Prodromal PD in Subjects With RBD

TypeobservationalSponsorDanish Research Centre for Magnetic ResonanceRan2026 to 2035Enrolled100ConditionsREM Sleep Behavior Disorder, Synucleinopathies, Parkinson's Disease (PD), Prodromal Parkinson's Disease
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  4. Article
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  6. Observational
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  8. Article
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  10. Fluid and Biopsy Based Biomarkers in Parkinson's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
  11. Article
  12. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 2 countries.

Mitchell G MiglisDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, USA.ORCID 0000-0001-8488-0313
Jennifer ZitserDepartment of Neurology, Tel Aviv Sourasky Medical Center, Affiliate of Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.ORCID 0000-0003-0200-6185
Logan SchneiderStanford Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Redwood City, CA, USA.ORCID 0000-0001-8729-5224
Emmanuel DuringDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, USA.
Safwan JaradehDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, USA.
Roy FreemanDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA.
Christopher H GibbonsDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA.
Beth Israel Deaconess Medical Center · USStanford Medicine · USStanford University · USTel Aviv University · ILVA Palo Alto Health Care System · US

Funding

Training CoreU54NS065736 · NINDS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI FREEMAN, ROY · 2009 to 2018
$11.6M
NINDS NIH HHS U54 NS065736
6 · The paper itself

Abstract

STUDY

objectivesTo define the clinical implications of cutaneous phosphorylated α-synuclein (p-syn) and its association with subjective and objective measures of autonomic impairment and clinical features including antidepressant use in isolated rapid eye movement (REM) sleep behavior disorder (iRBD).

methodsTwenty-five iRBD patients had quantified neurological and cognitive examinations, olfactory testing, questionnaires, autonomic function testing, and 3 punch skin biopsies (distal thigh, proximal thigh, neck). Skin biopsies were stained for the pan-axonal marker PGP 9.5 and co-stained with p-syn, and results were compared to 28 patients with Parkinson's disease (PD) and 18 healthy controls. Equal numbers of iRBD patients on and off antidepressants were recruited. The composite autonomic severity scale (CASS) was calculated for all patients.

resultsP-syn was detected 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 (CASS adrenergic r = 0.6, p < 0.05) and total autonomic impairment (CASS total r = 0.6, p < 0.05) on autonomic reflex testing in iRBD patients. These results were independent of the density of p-syn at each site. There was no correlation between p-syn and antidepressant use.

conclusionsIn patients with iRBD, the presence of cutaneous p-syn was detected in most patients and was associated with greater autonomic dysfunction on testing. Longitudinal follow-up will aid in defining the predictive role of both skin biopsy and autonomic testing in determining phenoconversion rates and future disease status.

Indexed as

Parkinson DiseasePrimary DysautonomiasREM Sleep Behavior Disorderalpha-SynucleinAutonomic Nervous SystemHumansalpha-SynucleinautonomiciRBDparasomniasParkinson’s diseaseRBDskin biopsy

Identifiers

PMID34244806
PMCPMC8664580
OpenAlexW3178801369

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.