Differential motor signatures in isolated and narcolepsy-related REM sleep behaviour disorder: a preliminary study

Journal article

Background: REM sleep behaviour disorder (RBD) is a prodrome of α-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. Methods: We retrospectively analyzed blinded video-polysomnographic scorings from 57 patients (iRBD n = 34; NT1-RBD n = 23). 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’s exact tests with Cohen’s h; the per-patient complex-event proportion used Mann–Whitney and Cliff’s δ (bootstrap 95% CI). Robustness checks comprised Beta-Binomial posteriors (Beta [1,1]) and patient-label permutation tests (10,000 permutations). Results: REM motor phenotypes diverged categorically. Lower-limb dominance occurred in 18/23 (78.3%) NT1-RBD vs. 7/34 (20.6%) iRBD (Fisher p < 0.0001; Cohen’s h ≈ +1.23), whereas upper-limb dominance occurred in 24/34 (70.6%) iRBD vs. 2/23 (8.7%) NT1-RBD (p < 0.0001; h ≈ −1.40). Any complex event was present in 27/34 (79.4%) iRBD vs. 3/23 (13.0%) NT1-RBD (p < 0.0001; h ≈ −1.46); violent enactments in 16/34 (47.1%) vs. 0/23 (0%) (p < 0.0001; h ≈ −1.51). The per-patient complex-event proportion was higher in iRBD [median 0.21 (0.05–0.33)] than NT1-RBD [0.00 (0.00–0.00)] (Mann–Whitney p < 0.0001; Cliff’s δ = −0.665; 95% CI −0.853 to −0.441). Event-level summaries were concordant; permutation p-values were 0.0001 for upper-limb involvement and 0.0083 for complex behaviour. Conclusion: 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.

Authors: Drakatos, P; Duncan, I; Wasserman, D; Gnoni, V; O’Regan, D

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Frontiers Media
• Journal: Frontiers in Neurology
• Volume: 16
• Article number: 1749306
• Publication date: 2026-01-14
• Acceptance date: 2025-12-23
• DOI: 10.3389/fneur.2025.1749306
• EISSN: 1664-2295
• ISSN: 1664-2295
• Language: English
• Keywords: video-polysomnography; narcolepsy type 1; orexin; sleep neurophysiology; isolated RBD; neurodegeneration; motor semiology; REM sleep behaviour disorder