Ikelos-Rating Scale: Validation of a Behavioural Severity Marker in REM Sleep Behaviour Disorder

The Ikelos-Rating Scale (Ikelos-RS) is a new, expert-interviewed and bedpartner-reported severity marker assessing frequency and expression of isolated REM sleep behaviour disorder (iRBD), a precursor of clinical α-synucleinopathies. This study aimed to validate the Ikelos-RS in 180 patients with three-night PSG-confirmed iRBD (68.4 ± 8.3 years; 139 m). Inter-rater (n = 45) and test-retest reliabilities (n = 25; 174 Ikelos-RS) were evaluated. For construct validity, correlation analyses were performed with: (1) Clinical Global Impressions-Severity (CGI-S; n = 151), (2) REM sleep without atonia (RWA) within videometry (n = 20), (3) RWA at initial diagnosis (n = 131) and changes over time (n = 36), (4) dopamine transporter scintigraphy (DaT-SPECT) at baseline and changes over time (n = 75). RWA- and DaT-SPECT-analyses were conducted for the whole sample ('all') and after excluding confounders ('cleaned'). Correlation analyses indicated high inter-rater (r _s  = 0.865, p < 0.001) and test-retest reliabilities (r _s  = 0.900, p < 0.001). Construct validity was supported by associations of Ikelos-RS with (1) CGI-S (r _s  = 0.845, p < 0.001), (2) RWA within videometric analysis (r _s  = 0.592, p = 0.006) and at baseline ('all': r _s  = 0.274, p = 0.002), (3) DaT-binding (z-scores) at baseline in right anterior putamen (AP) ('all': r _s  = -0.319, p = 0.005) and changes over time, most pronounced in right anterior putamen (AP) ('all': r _s  = -0.243, p = 0.035; 'cleaned': r _s  = -0.374, p = 0.008) and left posterior putamen (PP) ('all': r _s  = -0.259, p = 0.025; 'cleaned': r _s  = -0.319, p = 0.024). Given its high reliability and construct validity, demonstrated by associations with the best available severity markers DaT-binding ratios and RWA, Ikelos-RS appears to represent a reliable, valid and easy-to-use tool for measuring the severity of iRBD. Thus, Ikelos-RS may prove beneficial in research. Its suitability as a screening tool in older at-risk populations needs to be proven in future studies.