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

**Authors:** Panagis Drakatos, Iain Duncan, Danielle Wasserman, Valentina Gnoni, David O’Regan, Andrew W. Varga, Huiling Tan, Keyoumars Ashkan, Lea T. Grinberg, Liborio Parrino, Luigi Ferini-Strambi, Peter J. Goadsby, K. Ray Chaudhuri, Ivana Rosenzweig

PMC · DOI: 10.3389/fneur.2025.1749306 · Frontiers in Neurology · 2026-01-14

## TL;DR

This study finds that REM sleep behavior disorder in people with narcolepsy differs significantly from isolated cases, suggesting different underlying brain mechanisms.

## Contribution

The study identifies distinct motor patterns in REM sleep behavior disorder linked to narcolepsy versus isolated cases.

## Key findings

- Lower-limb motor dominance was much more common in narcolepsy-related RBD than in isolated RBD.
- Isolated RBD showed more complex and violent motor behaviors compared to narcolepsy-related RBD.
- Statistical robustness checks confirmed the significant differences in motor patterns between the two groups.

## Abstract

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.

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).

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.

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.

## Linked entities

- **Diseases:** narcolepsy type 1 (MONDO:0016158)

## Full-text entities

- **Diseases:** alpha-synucleinopathy (MESH:D000080874), violent (MESH:D001523), neurodegeneration (MESH:D019636), narcolepsy (MESH:D009290), Narcolepsy type 1 (MESH:C563534), orexin deficiency (MESH:D007153), RBD (MESH:D020187)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12847386/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12847386/full.md

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Source: https://tomesphere.com/paper/PMC12847386