Continuous REM sleep without atonia quantification improves prediction of phenoconversion to α-synucleinopathies in isolated REM sleep behavior disorder

Study objectives: isolated REM sleep behavior disorder (iRBD), characterized by REM sleep without atonia (RWA), is considered a prodromal stage of α-synucleinopathies. This study aims to evaluate the predictive potential for phenoconversion of cumulative RWA percentage (CRWA%) as a continuous quantification of RWA compared to conventional epoch-based methods. Methods: Baseline video-polysomnograms from 92 iRBD patients were analyzed. Eleven patients converted to α-synucleinopathies during follow-up (iRBD-CV), while the remaining patients did not (iRBD-NC). RWA quantification was performed using a validated in-house algorithm in mentalis (MT) and bilateral flexor digitorum superficialis (FDS) muscles. Receiver operating characteristic curves, Kaplan-Meier survival analysis, and Cox proportional hazards models were used to assess predictive performance. Results: The iRBD-CV group had significantly higher CRWA%, REM atonia index, and any RWA (using SINBAR and AASM methods) compared with the iRBD-NC group (p < 0.035). Among these metrics, CRWA% demonstrated the highest predictive performance, with an area under the curve (AUC) of 0.89 in the combined MT and FDS channels. Survival analysis showed that patients with CRWA% > 32.54 % had significantly reduced disease-free rates (p = 0.004), with 3-year and 5-year rates of 51.4 % and 25.7 %, respectively. Additionally, higher CRWA% was significantly associated with a higher phenoconversion risk (Hazard ratio = 1.063, p = 0.006). Conclusion: CRWA% provides a more precise and continuous approach to quantifying RWA, outperforming traditional methods in predicting phenoconversion to α-synucleinopathies in iRBD. These findings underscore the potential of CRWA% as a robust biomarker for early neurodegenerative progression.