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Misfolded α-Synuclein Assessment in the Skin and CSF by RT-QuIC in Isolated REM Sleep Behavior Disorder. | LitMetric

Misfolded α-Synuclein Assessment in the Skin and CSF by RT-QuIC in Isolated REM Sleep Behavior Disorder.

Neurology

From the Neurology Service (A.I., A.M.-L., G.M., M.S., A.A., J.S.C., C.G.), Sleep Centre, Hospital Clínic Barcelona, Universitat de Barcelona, IDIBAPS, CIBERNED: CB06/05/0018-ISCIII; IRCCS (A.M., S.D., M.R., S.B., C.Q., E.R., P.P.), Istituto delle Scienze Neurologiche di Bologna (ISNB); Department of Biomedical and Neuromotor Sciences (A.M., S.B., P.P.), University of Bologna; and Nuclear Medicine Service (A.P.), Hospital Clínic Barcelona, Biomedical Research Networking Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), ISCIII, Spain.

Published: May 2023

AI Article Synopsis

Article Abstract

Background And Objectives: Real-time quaking-induced conversion (RT-QuIC) assay detects misfolded α-synuclein (AS) in the skin and CSF of patients with the synucleinopathies Parkinson disease and dementia with Lewy bodies. Isolated REM sleep behavior disorder (IRBD) constitutes the prodromal stage of these synucleinopathies. We aimed to compare the ability of RT-QuIC to identify AS in the skin and CSF of patients with IRBD.

Methods: This was a cross-sectional study where consecutive patients with polysomnographic-confirmed IRBD and age-matched controls without RBD underwent skin biopsy and lumbar puncture the same day. Three-millimeter skin punch biopsies were obtained bilaterally in the cervical region from dorsal C7 and C8 dermatomes and in distal legs. RT-QuIC assessed AS in these 6 skin sites and the CSF.

Results: We recruited 91 patients with IRBD and 41 controls. In the skin, sensitivity to detect AS was 76.9% (95% CI 66.9-85.1), specificity 97.6% (95% CI 87.1-99.9) positive predictive value 98.6% (95% CI 91.0-99.8), negative predictive value 65.6% (95% CI 56.6-73.6), and accuracy 83.3% (95% CI 75.9-89.3). In the CSF, the sensitivity was 75.0% (95% CI 64.6-83.6), the specificity was 97.5% (95% CI 86.8-99.9), the positive predictive value was 98.5% (95% CI 90.5-99.8), the negative predictive value was 63.9% (95% CI 55.2-71.9), and the accuracy was 82.0% (95% CI 74.3-88.3). Results in the skin and CSF samples showed 99.2% agreement. Compared with negative patients, RT-QuIC AS-positive patients had a higher likelihood ratio of prodromal Parkinson disease ( < 0.001) and showed more frequently hyposmia ( < 0.001), dopamine transporter imaging single-photon emission CT deficit ( = 0.002), and orthostatic hypotension ( = 0.014). No severe or moderate adverse effects were reported. There was no difference between the percentage of participants reporting mild adverse events secondary to skin biopsy or lumbar puncture (9.1% vs 17.2%; = 0.053). One hundred and ten (83%) and 104 (80%) participants, respectively, stated they would accept to undergo skin biopsy and lumbar puncture again for research purposes.

Discussion: Our study in IRBD shows that (1) RT-QuIC detects AS in the skin and CSF with similar high sensitivity, specificity, and agreement, (2) AS RT-QuIC positivity is associated with supportive features and biomarkers of synucleinopathy, and (3) skin punch biopsy and lumbar puncture have comparable mild adverse effects, tolerance, and acceptance. RT-QuIC in the skin or CSF might represent a patient selection strategy for future neuroprotective trials targeting AS in IRBD.

Classification Of Evidence: This study provides Class III evidence that RT-QuIC-detected AS in the skin and CSF distinguishes patients with IRBD from controls.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10159765PMC
http://dx.doi.org/10.1212/WNL.0000000000207147DOI Listing

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