Automatic analysis of muscular activity in the flexor digitorum superficialis muscles: a fast screening method for rapid eye movement sleep without atonia.

STUDY OBJECTIVES: To identify a fast and reliable method for rapid eye movement (REM) sleep without atonia (RWA) quantification. METHODS: We analyzed 36 video-polysomnographies (v-PSGs) of isolated REM sleep behavior disorder (iRBD) patients and 35 controls' v-PSGs. Patients diagnosed with RBD had: i) RWA, quantified with a reference method, i.e. automatic and artifact-corrected 3-s Sleep Innsbruck Barcelona (SINBAR) index in REM sleep periods (RSPs, i.e. manually selected portions of REM sleep); and ii) v-PSG-documented RBD behaviors. We quantified RWA with other (semi)-automated methods requiring less human intervention than the reference one: the indices proposed by the SINBAR group (the 3-s and 30-s phasic flexor digitorum superficialis (FDS), phasic/"any"/tonic mentalis), and the REM atonia, short and long muscle activity indices (in mentalis/submentalis/FDS muscles). They were calculated in whole REM sleep (i.e. REM sleep scored following international guidelines), in RSPs, with and without manual artifact correction. Area under curves (AUC) discriminating iRBD from controls were computed. Using published cut-offs, the indices' sensitivity and specificity for iRBD identification were calculated. Apnea-hypopnea index in REM sleep (AHIREM) was considered in the analyses. RESULTS: RWA indices from FDS muscles alone had the highest AUCs and all of them had 100% sensitivity. Without manual RSP selection and artifact correction, the "30-s phasic FDS" and the "FDS long muscle activity" had the highest specificity (85%) with AHIREM < 15/h. RWA indices were less reliable when AHIREM≥15/h. CONCLUSIONS: If AHIREM<15/h, FDS muscular activity in whole REM sleep and without artifact correction is fast and reliable to rule out RWA.

Analysis of REM sleep without atonia in 22q11.2 deletion syndrome determined by domiciliary polysomnography: a cross sectional study.

STUDY OBJECTIVES: Our aim is to evaluate the presence of REM sleep without atonia (RWA), the objective hallmark of REM sleep Behaviour Disorder (RBD), as prodromal marker of Parkinson's disease (PD), in an adult cohort of 22q11.2 deletion syndrome (22qDS). METHODS: Sleep quality was assessed by means of Pittsburgh quality scale index (PSQI), and RBD symptoms by means of RBD questionnaire-Hong-Kong (RBDQ-HK). Attended domiciliary video-Polysomnography (v-PSG) were performed in 26 adults (18-51 years, 14 females) 22qDS patients. Electromyogram during REM sleep was analyzed by means of SINBAR procedure at 3-second time resolution (miniepochs). RESULTS: An overall poor sleep quality was observed in the cohort and high RBDQ-HK score in 7 of the 26 patients, two additional patients with positive dream enactment reported by close relatives had low score of RBDQ-HK. Nevertheless, SINBAR RWA scores were lower than cut-off threshold for RWA (mean 5.5%, range 0-12.2%). TST and the percentage of light sleep (N1) were increased, with preserved proportions of N2 and N3. Participants reported poor quality of sleep (mean PSQI > 5), with prolonged sleep latency in the v-PSG. No subjects exhibit evident dream enactment episodes during recording sessions. CONCLUSIONS: RWA was absent in the studied cohort of 22qDS adult volunteers according to validated polysomnographic criteria. High RBDQ-HK scores do not correlate with v-PSG results among 22qDS individuals.

Flexor digitorum superficialis muscular activity is more reliable than mentalis muscular activity for rapid eye movement sleep without atonia quantification: A study of interrater reliability for artifact correction in the context of semiautomated scoring of rapid eye movement sleep without atonia.

STUDY OBJECTIVES: To evaluate interrater reliability for artifact correction in the context of semiautomated quantification of rapid eye movement (REM) sleep without atonia (RWA) in the mentalis and flexor digitorum superficialis (FDS) muscles. METHODS: We included video-polysomnographies of 14 subjects with apnea-hypopnea index in REM sleep (AHIREM) < 15/h and 11 subjects with AHIREM ≥ 15/h. Eight subjects had isolated REM sleep behavior disorder. A validated algorithm (www.osg.be) automatically scored phasic and "any" EMG activity in the mentalis muscle, and phasic EMG activity in the FDS muscles. Four independent expert scorers performed artifact correction according to the SINBAR (Sleep Innsbruck Barcelona) recommendations. Interrater reliability for artifact correction was computed with B-statistics. The variability across scorers of four RWA indices (phasic mentalis, "any" mentalis, phasic FDS and SINBAR-i.e. "any" mentalis and/or phasic FDS-EMG activity indices) was computed. With Friedman tests, we compared B-statistics obtained for mentalis and FDS muscles, and the variability of the RWA indices. Influence of AHIREM and REM sleep behavior disorder (RBD) diagnosis on the RWA indices variability was evaluated with linear regressions. RESULTS: Interrater reliability for artifact correction was higher in the FDS than in the mentalis muscle (p < 0.001). Phasic FDS activity was minimally affected by artifacts. Accordingly, the phasic FDS EMG activity index had the lowest variability across scorers (p < 0.001). Variability across scorers of the RWA indices including the mentalis muscle increased with AHIREM and was independent from RBD diagnosis. CONCLUSIONS: Due to the consistently found low number of artifacts, phasic FDS activity is a reliable measure of RWA.

Automated 3D video analysis of lower limb movements during REM sleep: a new diagnostic tool for isolated REM sleep behavior disorder.

STUDY OBJECTIVES: The differentiation of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) or its prodromal phase (prodromal RBD) from other disorders with motor activity during sleep is critical for identifying α-synucleinopathy in an early stage. Currently, definite RBD diagnosis requires video polysomnography (vPSG). The aim of this study was to evaluate automated 3D video analysis of leg movements during REM sleep as objective diagnostic tool for iRBD. METHODS: A total of 122 participants (40 iRBD, 18 prodromal RBD, 64 participants with other disorders with motor activity during sleep) were recruited among patients undergoing vPSG at the Sleep Disorders Unit, Department of Neurology, Medical University of Innsbruck. 3D videos synchronous to vPSG were recorded. Lower limb movements rate, duration, extent, and intensity were computed using a newly developed software. RESULTS: The analyzed 3D movement features were significantly increased in subjects with iRBD compared to prodromal RBD and other disorders with motor activity during sleep. Minor leg jerks with a duration < 2 seconds discriminated with the highest accuracy (90.4%) iRBD from other motor activity during sleep. Automatic 3D analysis did not differentiate between prodromal RBD and other disorders with motor activity during sleep. CONCLUSIONS: Automated 3D video analysis of leg movements during REM sleep is a promising diagnostic tool for identifying subjects with iRBD in a sleep laboratory population and is able to distinguish iRBD from subjects with other motor activities during sleep. For future application as a screening, further studies should investigate usefulness of this tool when no information about sleep stages from vPSG is available and in the home environment.

Precision Medicine in Rapid Eye Movement Sleep Behavior Disorder.

In recent years, the diagnostic approach to rapid eye movement (REM) sleep behavior disorder (RBD) has become more objective and accurate. This was achieved mainly by introduction of methods to exactly quantify electromyographic (EMG) activity in various muscles during REM sleep. The most established muscle combination for RBD diagnosis is the mentalis and upper extremity EMG. Computer-assisted systems for this analysis have been described, and an increasing number of studies looked into analysis of video events. Recently, prodromal phases of isolated RBD have been recognized.

Comparison Between Automatic and Visual Scorings of REM Sleep Without Atonia for the Diagnosis of REM Sleep Behavior Disorder in Parkinson Disease.

Study Objectives: To compare three different methods, two visual and one automatic, for the quantification of rapid eye movement (REM) sleep without atonia (RSWA) in the diagnosis of REM sleep behavior disorder (RBD) in Parkinson's disease (PD) patients. Methods: Sixty-two consecutive patients with idiopathic PD underwent video-polysomnographic recording and showed more than 5 minutes of REM sleep. The electromyogram during REM sleep was analyzed by means of two visual methods (Montréal and SINBAR) and one automatic analysis (REM Atonia Index or RAI). RBD was diagnosed according to standard criteria and a series of diagnostic accuracy measures were calculated for each method, as well as the agreement between them. Results: RBD was diagnosed in 59.7% of patients. The accuracy (85.5%), receiver operating characteristic (ROC) area (0.833) and Cohen's K coefficient (0.688) obtained with RAI were similar to those of the visual parameters. Visual tonic parameters, alone or in combination with phasic activity, showed high values of accuracy (93.5-95.2%), ROC area (0.92-0.94), and Cohen's K (0.862-0.933). Similarly, the agreement between the two visual methods was very high, and the agreement between each visual methods and RAI was substantial. Visual phasic measures alone performed worse than all the other measures. Conclusion: The diagnostic accuracy of RSWA obtained with both visual and automatic methods was high and there was a general agreement between methods. RAI may be used as the first line method to detect RSWA in the diagnosis of RBD in PD, together with the visual inspection of video-recorded behaviors, while the visual analysis of RSWA might be used in doubtful cases.

REM sleep behavior disorder (RBD): Update on diagnosis and treatment.

BACKGROUND: REM sleep behavior disorder (RBD) is parasomnia characterized by dream enactment and enabled by disruption of physiological muscle atonia during REM sleep. Over the past few years, diagnostic criteria and the methods used to confirm diagnosis have been updated. OBJECTIVE: In this review article, the current knowledge regarding RBD diagnosis and treatment is presented. METHODS: A selective literature search was carried out. RESULTS AND DISCUSSION: Although several RBD screening questionnaires have been developed, diagnosis can only be definitely confirmed on the basis of polysomnography. New methods for scoring electromyography (EMG) activity during REM sleep have been proposed during recent years and cutoff values have been established. The latest cutoff values for scoring EMG activity during REM sleep are included in the International Classification of Sleep Disorders (ICSD). The cutoff of 27 % muscle activity during REM sleep suggested by the Sleep Innsbruck Barcelona (SINBAR) group was also included in the third edition of the ICSD. The best-researched treatments for RBD are clonazepam and melatonin.

Long-Term Follow-up Investigation of Isolated Rapid Eye Movement Sleep Without Atonia Without Rapid Eye Movement Sleep Behavior Disorder: A Pilot Study.

STUDY OBJECTIVES: Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a harbinger of synuclein-mediated neurodegenerative diseases. It is unknown if this also applies to isolated REM sleep without atonia (RWA). We performed a long-term follow-up investigation of subjects with isolated RWA. METHODS: Participants were recruited from 50 subjects with isolated RWA who were identified at the sleep laboratory of the Department of Neurology at the Medical University of Innsbruck between 2003 and 2005. Eligible subjects underwent follow-up clinical examination, polysomnography, and assessment of neurodegenerative biomarkers (cognitive impairment, finger speed deficit, impaired color vision, olfactory dysfunction, orthostatic hypotension, and substantia nigra hyperechogenicity). RESULTS: After a mean of 8.6 ± 0.9 y, 1 of 14 participating subjects (7.3%) progressed to RBD. Ten of 14 RWA subjects (71.4%) were positive for at least one neurodegenerative biomarker. Substantia nigra hyperechogenicity and presence of mild cognitive impairment were both present in 4 of 14 subjects with isolated RWA. Electromyographic activity measures increased significantly from baseline to follow-up polysomnography ("any" mentalis and both anterior tibialis muscles: 32.5 ± 9.4 versus 52.2 ± 16.6%; p = 0.004). CONCLUSION: This study provides first evidence that isolated RWA is an early biomarker of synuclein-mediated neurodegeneration. These results will have to be replicated in larger studies with longer observational periods. If confirmed, these disease findings have implications for defining at-risk cohorts for Parkinson disease.

Quantitative assessment of isolated rapid eye movement (REM) sleep without atonia without clinical REM sleep behavior disorder: clinical and research implications.

BACKGROUND: Rapid eye movement (REM) sleep without atonia (RWA) is observed in some patients without a clinical history of REM sleep behavior disorder (RBD). It remains unknown whether these patients meet the refined quantitative electromyographic (EMG) criteria supporting a clinical RBD diagnosis. We quantitatively evaluated EMG activity and investigated its overnight distribution in patients with isolated qualitative RWA. METHODS: Fifty participants with an incidental polysomnographic finding of RWA (isolated qualitative RWA) were included. Tonic, phasic, and 'any' EMG activity during REM sleep on PSG were quantified retrospectively. RESULTS: Referring to the quantitative cut-off values for a polysomnographic diagnosis of RBD, 7/50 (14%) and 6/50 (12%) of the patients showed phasic and 'any' EMG activity in the mentalis muscle above the respective cut-off values. No patient was above the cut-off value for tonic EMG activity or phasic EMG activity in the anterior tibialis muscles. Patients with RWA above the cut-off value showed higher amounts of RWA during later REM sleep periods. CONCLUSIONS: This is the first study showing that some subjects with incidental RWA meet the refined quantitative EMG criteria for a diagnosis of RBD. Future longitudinal studies must investigate whether this subgroup with isolated qualitative RWA is at an increased risk of developing fully expressed RBD and/or neurodegenerative disease.

Normative EMG values during REM sleep for the diagnosis of REM sleep behavior disorder.

BACKGROUND: Correct diagnosis of rapid eye movement sleep behavior disorder (RBD) is important because it can be the first manifestation of a neurodegenerative disease, it may lead to serious injury, and it is a well-treatable disorder. We evaluated the electromyographic (EMG) activity in the Sleep Innsbruck Barcelona (SINBAR) montage (mentalis, flexor digitorum superficialis, extensor digitorum brevis) and other muscles to obtain normative values for the correct diagnosis of RBD for clinical practice. SETTING: Two university hospital sleep disorder centers. PARTICIPANTS: Thirty RBD patients (15 idiopathic [iRBD], 15 with Parkinson disease [PD]) and 30 matched controls recruited from patients with effectively treated sleep related breathing disorders. INTERVENTIONS: Not applicable. METHODS AND RESULTS: Participants underwent video-polysomnography, including registration of 11 body muscles. Tonic, phasic, and "any" (any type of EMG activity, irrespective of whether it consisted of tonic, phasic or a combination of both) EMG activity was blindly quantified for each muscle. When choosing a specificity of 100%, the 3-sec miniepoch cutoff for a diagnosis of RBD was 18% for "any" EMG activity in the mentalis muscle (area under the curve [AUC] 0.990). Discriminative power was higher in upper limb (100% specificity, AUC 0.987-9.997) than in lower limb muscles (100% specificity, AUC 0.813-0.852). The combination of "any" EMG activity in the mentalis muscle with both phasic flexor digitorum superficialis muscles yielded a cutoff of 32% (AUC 0.998) for patients with iRBD and with PD-RBD. CONCLUSION: For the diagnosis of iRBD and RBD associated with PD, we recommend a polysomnographic montage quantifying "any" (any type of EMG activity, irrespective of whether it consisted of tonic, phasic or a combination of both) EMG activity in the mentalis muscle and phasic EMG activity in the right and left flexor digitorum superficialis muscles in the upper limbs with a cutoff of 32%, when using 3-sec miniepochs.