{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:07:23Z","timestamp":1785856043618,"version":"3.56.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["103952\/Z\/14\/Z"],"award-info":[{"award-number":["103952\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      REM sleep behaviour disorder (RBD) is a prodrome of\n                      <jats:italic>\u03b1<\/jats:italic>\n                      -synucleinopathy, yet mechanistic pathways are unresolved. Narcolepsy type 1 with RBD (NT1-RBD) provides a human model of orexin deficiency. We tested whether REM motor semiology differs categorically between isolated RBD (iRBD) and NT1-RBD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed blinded video-polysomnographic scorings from 57 patients (iRBD\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f34; NT1-RBD\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f23). Across 857 REM events (iRBD 717; NT1-RBD 140), we classified topography (head\/neck, trunk, upper, lower limbs), complexity (elementary vs. complex), content (scenic, violent, self-referential), vocal\/orofacial features, spatial distribution and laterality using a pre-specified codebook. The patient was the primary unit of inference. Binary features used Fisher\u2019s exact tests with Cohen\u2019s\n                      <jats:italic>h<\/jats:italic>\n                      ; the per-patient complex-event proportion used Mann\u2013Whitney and Cliff\u2019s\n                      <jats:italic>\u03b4<\/jats:italic>\n                      (bootstrap 95% CI). Robustness checks comprised Beta-Binomial posteriors (Beta [1,1]) and patient-label permutation tests (10,000 permutations).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      REM motor phenotypes diverged categorically. Lower-limb dominance occurred in 18\/23 (78.3%) NT1-RBD vs. 7\/34 (20.6%) iRBD (Fisher\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.0001; Cohen\u2019s\n                      <jats:italic>h<\/jats:italic>\n                      \u202f\u2248\u202f+1.23), whereas upper-limb dominance occurred in 24\/34 (70.6%) iRBD vs. 2\/23 (8.7%) NT1-RBD (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.0001;\n                      <jats:italic>h<\/jats:italic>\n                      \u202f\u2248\u202f\u22121.40). Any complex event was present in 27\/34 (79.4%) iRBD vs. 3\/23 (13.0%) NT1-RBD (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.0001;\n                      <jats:italic>h<\/jats:italic>\n                      \u202f\u2248\u202f\u22121.46); violent enactments in 16\/34 (47.1%) vs. 0\/23 (0%) (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.0001;\n                      <jats:italic>h<\/jats:italic>\n                      \u202f\u2248\u202f\u22121.51). The per-patient complex-event proportion was higher in iRBD [median 0.21 (0.05\u20130.33)] than NT1-RBD [0.00 (0.00\u20130.00)] (Mann\u2013Whitney\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.0001; Cliff\u2019s\n                      <jats:italic>\u03b4<\/jats:italic>\n                      \u202f=\u202f\u22120.665; 95% CI \u22120.853 to \u22120.441). Event-level summaries were concordant; permutation\n                      <jats:italic>p<\/jats:italic>\n                      -values were 0.0001 for upper-limb involvement and 0.0083 for complex behaviour.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>iRBD and NT1-RBD exhibit qualitatively distinct REM motor phenotypes: upper-body-dominant, complex\/scenic behaviours in iRBD versus elementary, predominantly bilateral lower-limb behaviours with notable trunk recruitment in NT1-RBD, supported by large effect sizes and convergent robustness checks. These findings motivate mechanistic studies of hypothalamic-brainstem-cortical integration in REM and suggest that semiological profiling may aid stratification in prodromal neurodegeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1749306","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T06:40:03Z","timestamp":1768372803000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Differential motor signatures in isolated and narcolepsy-related REM sleep behaviour disorder: a preliminary study"],"prefix":"10.3389","volume":"16","author":[{"given":"Panagis","family":"Drakatos","sequence":"first","affiliation":[{"name":"Sleep Disorders Centre, Guy\u2019s and St Thomas\u2019 Hospital (GSTT NHS)","place":["London, United Kingdom"]},{"name":"Faculty of Life Sciences and Medicine, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Duncan","sequence":"additional","affiliation":[{"name":"Sleep Disorders Centre, Guy\u2019s and St Thomas\u2019 Hospital (GSTT NHS)","place":["London, United Kingdom"]},{"name":"Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Sleep Disorders Centre, Guy\u2019s and St Thomas\u2019 Hospital (GSTT NHS)","place":["London, United Kingdom"]},{"name":"Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Gnoni","sequence":"additional","affiliation":[{"name":"Sleep Disorders Centre, Guy\u2019s and St Thomas\u2019 Hospital (GSTT NHS)","place":["London, United Kingdom"]},{"name":"Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"O\u2019Regan","sequence":"additional","affiliation":[{"name":"Sleep Disorders Centre, Guy\u2019s and St Thomas\u2019 Hospital (GSTT NHS)","place":["London, United Kingdom"]},{"name":"Faculty of Life Sciences and Medicine, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Varga","sequence":"additional","affiliation":[{"name":"Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Tan","sequence":"additional","affiliation":[{"name":"MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyoumars","family":"Ashkan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, King\u2019s College Hospital Foundation Trust","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea T.","family":"Grinberg","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic","place":["Jacksonville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liborio","family":"Parrino","sequence":"additional","affiliation":[{"name":"Sleep Disorders Centre, Parma University Hospital","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Ferini-Strambi","sequence":"additional","affiliation":[{"name":"Sleep Disorders Center, Universit\u00e0 Vita-Salute San Raffaele","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Goadsby","sequence":"additional","affiliation":[{"name":"NIHR-Wellcome Trust King\u2019s Clinical Research Facility, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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