RESUMO
STUDY OBJECTIVES: Accurate diagnosis of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is crucial due to its injury potential and neurological prognosis. We aimed to analyze visual and automated REM sleep without atonia (RSWA) diagnostic thresholds applicable in varying clinical presentations in a contemporary cohort of patients with iRBD using submentalis (SM) and individual bilateral flexor digitorum superficialis (FDS) and anterior tibialis electromyography limb recordings during polysomnography. METHODS: We analyzed RSWA in 20 patients with iRBD and 20 age-, REM-, apnea-hypopnea index-matched controls between 2017 and 2022 for phasic burst durations, density of phasic, tonic, and "any" muscle activity (number of 3-second mini-epochs containing phasic or tonic muscle activity divided by the total number of REM sleep 3-second mini-epochs), and automated Ferri REM atonia index (RAI). Group RSWA metrics were comparatively analyzed. Receiver operating characteristic curves determined optimized area under the curve (AUC) and maximized specificity and sensitivity diagnostic iRBD RSWA thresholds. RESULTS: All mean RSWA metrics were higher in patients with iRBD than in controls (P < .05), except for selected anterior tibialis measures. Optimized, maximal specificity AUC diagnostic cutoffs for coprimary outcomes were: SM "any" 6.5%, 14.0% (AUC = 92.5%) and combined SM+FDS "any" 15.1%, 27.4% (AUC = 95.8%), while SM burst durations were 0.72, and 0.72 seconds (AUC 90.2%) and FDS RAI = 0.930, 0.888 (AUC 92.8%). CONCLUSIONS: This study provides evidence for current quantitative RSWA diagnostic thresholds in chin and individual 4 limb muscles applicable in different iRBD clinical settings and confirms the key value of SM or SM+FDS to assure accurate iRBD diagnosis. Evolving iRBD recognition underscores the necessity of continuous assessment with future large, prospective, well-harmonized, multicenter polysomnographic analyses. CITATION: Leclair-Visonneau L, Feemster JC, Bibi N, et al. Contemporary diagnostic visual and automated polysomnographic REM sleep without atonia thresholds in isolated REM sleep behavior disorder. J Clin Sleep Med. 2024;20(2):279-291.
Assuntos
Transtorno do Comportamento do Sono REM , Sono REM , Humanos , Hipotonia Muscular/diagnóstico , Músculo Esquelético , Transtorno do Comportamento do Sono REM/diagnóstico , Sono REM/fisiologia , Estudos de Casos e ControlesRESUMO
BACKGROUND: Isolated REM sleep behavior disorder (RBD) is a potentially injurious parasomnia lacking an established treatment. Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist with 5-HT1A receptor agonist activity that has demonstrated efficacy in patients with schizophrenia. In a single dose challenge study in humans, ulotaront 50 mg demonstrated significant REM suppressant effects. We now report post-hoc exploratory analyses designed to evaluate the effect of ulotaront on quantitative REM sleep without atonia (RSWA). METHODS: Young healthy adult men (ages 19-35) were randomized to double-blind, cross-over treatment (after 7-day wash-out) with single doses of ulotaront (50 mg or 10 mg) versus placebo followed by polysomnography (PSG) on each of the nights following treatment. Quantitative RSWA was analyzed in a blinded fashion using established visual and automated methods. RESULTS: Subjects received 50 mg (n = 11) or 10 mg (n = 9) of ulotaront. Treatment with ulotaront 50 mg was associated with lower RSWA (p < 0.05), with greatest RSWA reduction (vs. placebo) observed in subjects with RSWA levels above the mean on the baseline night. RSWA levels were similar between treatment with ulotaront 10 mg and placebo. CONCLUSION: Treatment with ulotaront 50 mg (but not 10 mg) was associated with reductions in RSWA levels in healthy subjects, especially in subjects with higher baseline RSWA levels, providing proof-of-concept for ulotaront efficacy in reducing RSWA levels. However, whether ulotaront might have efficacy as a treatment for human RBD awaits double-blind trials with ulotaront in clinical RBD populations.
Assuntos
Transtorno do Comportamento do Sono REM , Sono REM , Masculino , Adulto , Humanos , Adulto Jovem , Voluntários Saudáveis , Hipotonia Muscular , Transtorno do Comportamento do Sono REM/complicaçõesRESUMO
STUDY OBJECTIVES: To evaluate whether or not the apnea-hypopnea index (AHI) from a peripheral arterial tonometry (PAT) home sleep apnea test (HSAT) is equivalent to the AHI provided by the mean of one, three, or seven nights from the Withings Sleep Analyzer (WSA) under-mattress device. METHODS: We prospectively enrolled patients with suspected OSA in whom a PAT-HSAT was ordered. Eligible patients used the WSA for seven to nine nights. PAT data were scored using the device's intrinsic machine learning algorithms to arrive at the AHI using both 3% and 4% desaturation criteria for hypopnea estimations (PAT3%-AHI and PAT4%-AHI, respectively). These were then compared with the WSA-estimated AHI (WSA-AHI). RESULTS: Of 61 patients enrolled, 35 completed the study with valid PAT and WSA data. Of the 35 completers 16 (46%) had at least moderately severe OSA (PAT3%-AHI ≥ 15). The seven-night mean WSA-AHI was 2.13 (95%CI = - 0.88, 5.14) less than the PAT3%-AHI, but 5.64 (95%CI = 2.54, 8.73) greater than the PAT4%-AHI. The accuracy and area under the receiver operating curve (AUC) using the PAT3%-AHI ≥ 15 were 77% and 0.87 and for PAT4%-AHI ≥ 15 were 77% and 0.85, respectively. The one-, three-, or seven-night WSA-AHI were not equivalent to either the 3% or 4% PAT-AHI (equivalency threshold of ± 2.5 using the two one-sided t-test method). CONCLUSIONS: The WSA derives estimates of the AHI unobtrusively over many nights, which may prove to be a valuable clinical tool. However, the WSA-AHI over- or underestimates the PAT-AHI in clinical use, and the appropriate use of the WSA in clinical practice will require further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04778748.
Assuntos
Apneia Obstrutiva do Sono , Sono , Humanos , Sensibilidade e Especificidade , Apneia Obstrutiva do Sono/diagnóstico , Polissonografia , ManometriaRESUMO
BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) occurs occasionally in essential tremor (ET), but polysomnographic REM sleep without atonia (RSWA) analyses have been sparse. OBJECTIVE: To characterize the amount and distribution of polysomnographic RSWA, the electrophysiologic substrate of RBD, in patients with Parkinson's disease (PD) and ET. METHODS: We analyzed quantitative RSWA in 73 patients: PD (23), ET (23), and age-sex-matched controls (27). None had dream-enactment behavior history or received antidepressants. Phasic, tonic, "any," and phasic-burst duration RSWA measures were calculated in the submentalis (SM) and anterior tibialis (AT) muscles. The automated REM atonia index (RAI) was also determined. Statistical analysis was performed by Kruskal-Wallis rank-sum and Mann-Whitney tests. RESULTS: SM phasic RSWA was significantly greater for PD than ET patients and controls (12.5% ± 12.8% vs. 4.9% ± 6.7%, 3.9% ± 2.6%), as was SM "any" (13.54% ± 14.30% vs. 5.2% ± 7.6%, 4.2% ± 2.6%). RAI was significantly lower in PD than in ET and controls (0.78 ± 0.23 vs. 0.92 ± 0.09 vs. 0.90 ± 0.17, P ≤ 0.005), but no different between ET and controls. AT phasic and "any" RSWA was similar between the 3 groups. ET and control RSWA was similar in all measures. Two ET patients (8.7%) had SM RSWA similar to PD patients. CONCLUSIONS: Elevated SM RSWA distinguished PD from ET in patients without dream-enactment symptoms and occurs frequently in PD patients, and in isolated tremor suggests underlying synucleinopathy. Prospective studies will further validate these findings.