Automated explainable wavelet-based sleep scoring system for a population suspected with insomnia, apnea and periodic leg movement.

Sleep is an integral and vital component of human life, contributing significantly to overall health and well-being, but a considerable number of people worldwide experience sleep disorders. Sleep disorder diagnosis heavily depends on accurately classifying sleep stages. Traditionally, this classification has been performed manually by trained sleep technologists that visually inspect polysomnography records. However, in order to mitigate the labor-intensive nature of this process, automated approaches have been developed. These automated methods aim to streamline and facilitate sleep stage classification. This study aims to classify sleep stages in a dataset comprising subjects with insomnia, PLM, and sleep apnea. The dataset consists of PSG recordings from the multi-ethnic study of atherosclerosis (MESA) cohort of the national sleep research resource (NSRR), including 2056 subjects. Among these subjects, 130 have insomnia, 39 suffer from PLM, 156 have sleep apnea, and the remaining 1731 are classified as good sleepers. This study proposes an automated computerized technique to classify sleep stages, developing a machine-learning model with explainable artificial intelligence (XAI) capabilities using wavelet-based Hjorth parameters. An optimal biorthogonal wavelet filter bank (BOWFB) has been employed to extract subbands (SBs) from 30 seconds of electroencephalogram (EEG) epochs. Three EEG channels, namely: Fz_Cz, Cz_Oz, and C4_M1, are employed to yield an optimum outcome. The Hjorth parameters extracted from SBs were then fed to different machine learning algorithms. To gain an understanding of the model, in this study, we used SHAP (Shapley Additive explanations) method. For subjects suffering from the aforementioned diseases, the model utilized features derived from all channels and employed an ensembled bagged trees (EnBT) classifier. The highest accuracy of 86.8%, 87.3%, 85.0%, 84.5%, and 83.8% is obtained for the insomniac, PLM, apniac, good sleepers and complete datasets, respectively. Using these techniques and datasets, the study aims to enhance sleep stage classification accuracy and improve understanding of sleep disorders such as insomnia, PLM, and sleep apnea.

Manual scoring of periodic limb movements in children: is it still necessary?

OBJECTIVE: Although manual scoring has been classically considered the gold standard to identify periodic leg movements (PLM), it is a very time consuming and expensive process, also subject to variability in interpretation. In the last decades, different authors have observed reasonably good agreement between automated PSG scoring algorithms and manual scoring in adults, according to established criteria. We aim to compare the automatic software analysis of our polysomnogram with the manual staging in children with sleep-disordered breathing. METHODS: We performed a semiautomatic method, in which an experienced technician watched the video recording and removed from the automatic analysis those movements that did not correspond to true candidate leg movement (LM). RESULTS: A total of 131 PSGs were studied; applying the established criteria, 65 children were diagnosed of obstructive sleep apnea, and 66 presented snoring but with no sleep apnea. The mean age was 6.7 years (±1.7) and twenty-five children (19.08 %) had a PLMI >5/h. Statistical differences were found not only for PLMI (manual: 2.20 (0.7, 4.1) vs automatic (6.4 (3.85,9.5); p < 0.001), but for almost of all indexes assessed between the automatic and the manual scoring analysis. The level of concordance was only moderate for PLM index (0.63 [0.51-0.72]); showing that, unlike the articles published in the adult population, automatic analysis is not accurate in children and, manually or semi-automatically analysis as ours need to be done. CONCLUSION: It seems that PLM detection algorithm might work accurately but, the real need would be a true LM detection algorithm.

Elevated periodic limb movement index is associated with hypoxemia in children with early onset scoliosis.

PURPOSE: Patients with early onset scoliosis are at high risk of sleep disordered breathing, sleep disruption, and adverse consequences of poor sleep. In this study, we aim to assess the prevalence of periodic limb movements of sleep in a cohort of children with early onset scoliosis and identify factors that correlate with the presence of periodic limb movements. METHODS: This is a retrospective chart review of 40 patients with EOS (ages 1-17 years) who underwent a PSG from 2003 through 2019. Data collected included age, sex, and polysomnography parameters. Descriptive statistics were used: independent T test and Pearson correlation. RESULTS: The average age was 9.6 years (SD 5.2); 22 were female. Eleven patients (27.5%) had elevated periodic limb movement index (PLMI) (≥ 5). Those with PLMI ≥ 5 had arousal index of 15.4 (SD 7.2) and those with normal PLMI having an arousal index of 9.4 (SD 4.9); this reached statistical significance (p < 0.05). Those with elevated PLMI spent 4.9 (SD 8.3) minutes with saturations below 88%, while those with normal PLMI spent 1.0 (SD 1.8); this was statistically significant. There was a moderate positive correlation between arousal index, hypoxemia, and PLMI. CONCLUSION: The study suggests that children with early onset scoliosis have higher frequency of periodic limb movements during sleep, and these may be correlated with increased arousal and with hypoxemia.

Periodic limb movement disorder in children: A systematic review.

This systematic review evaluates the scientific literature on pediatric periodic limb movement disorder (PLMD), adhering to PRISMA guidelines and utilizing PICOS criteria. The search across PubMed, EMBASE, and Scopus yielded 331 articles, with 17 meeting inclusion criteria. Diagnostic criteria evolved, with polysomnography and PLMS index ≥5 required since 2003. Also, PLMD diagnosis mandates clinical consequences like insomnia, hypersomnia, and fatigue, excluding comorbidities causing sleep disruption. Prevalence in children is low (0.3%), emphasizing the need for meticulous investigation. Comorbidities, particularly the bidirectional relationship with ADHD, were explored. Challenges in diagnosis and understanding arise from overlapping conditions such as sleep disordered breathing, psychotropic medication, and criteria non-adherence. Despite generally good study quality, weaknesses include sample size justification and biases. The periodic leg movement index shows high sensitivity but low specificity, underscoring strict diagnostic criteria adherence. Diverse metrics for symptoms necessitate standardized approaches. Family history of RLS in children with PLMD suggests unexplored aspects. Treatment, mainly iron supplementation, lacks standardized assessment metrics. The review emphasizes diagnostic and treatment challenges, recommending unbiased studies with precise techniques. Comprehensive research, quantifying PLMS and objectively assessing sleep parameters, is crucial for advancing understanding in pediatric PLMD. PROSPERO REGISTRATION NUMBER: CRD42021251406.

Association of Periodic Limb Movements and Obstructive Sleep Apnea With Risk of Cardiovascular Disease and Mortality.

BACKGROUND: Obstructive sleep apnea is a well-established risk factor for cardiovascular disease (CVD). Recent studies have also linked periodic limb movements during sleep to CVD. We aimed to determine whether periodic limb movements during sleep and obstructive sleep apnea are independent or synergistic factors for CVD events or death. METHODS AND RESULTS: We examined data from 1049 US veterans with an apnea-hypopnea index (AHI) <30 events/hour. The primary outcome was incident CVD or death. Cox proportional hazards regression assessed the relationships between the AHI, periodic limb movement index (PLMI), and the AHI×PLMI interaction with the primary outcome. We then examined whether AHI and PLMI were associated with primary outcome after adjustment for age, sex, race and ethnicity, obesity, baseline risk of mortality, and Charlson Comorbidity Index. During a median follow-up of 5.1 years, 237 of 1049 participants developed incident CVD or died. Unadjusted analyses showed an increased risk of the primary outcome with every 10-event/hour increase in PLMI (hazard ratio [HR], 1.08 [95% CI, 1.05-1.13]) and AHI (HR, 1.17 [95% CI, 1.01- 1.37]). Assessment associations of AHI and PLMI and their interaction with the primary outcome revealed no significant interaction between PLMI and AHI. In fully adjusted analyses, PLMI, but not AHI, was associated with an increased risk of primary outcome: HR of 1.05 (95% CI, 1.00-1.09) per every 10 events/hour. Results were similar after adjusting with Framingham risk score. CONCLUSIONS: Our study revealed periodic limb movements during sleep as a risk factor for incident CVD or death among those who had AHI <30 events/hour, without synergistic association between periodic limb movements during sleep and obstructive sleep apnea.

Generalised linear model of periodic limb movements.

During sleep, the lower extremities exhibit periodic repetitive movements which are referred to as Period Limb Movement (PLM). Polysomnography (PSG) is the gold standard for diagnosing periodic limb movement disorder. The frequency of PLM episodes per hour of sleep (PLMI) determines the severity of the condition. PLM are generated by a dynamic process, however PLMI measures only the average PLM rate and does not capture the dynamic properties of PLM. Here, we characterise PLM dynamics using a generalised dynamic model as a function of sleep stage, timing of past PLM events and adjacent sleep disordered-breathing events. We analysed PSG recordings of 237 men and 222 women enrolled in the Multi-ethnic Study of Atherosclerosis (MESA) dataset to model dynamic PLM features. We statistically analysed whether these dynamics are associated with sex, age, and BMI. Modelling suggests instantaneous PLM rates are greater in men than women and higher in N1 and N2 non-rapid eye movement sleep than N3 and rapid eye movement sleep. The generalised model constitutes statistically robust approach towards the characterisation of periodic limb movement.Clinical Relevance- The generalised model may enable differentiated diagnostics of periodic limb movement disorder.

[Restless sleep disorder a new entity to considered in children]. / Trastorno de sueño inquieto: una nueva entidad clínica a considerar en niños.

Restless sleep disorder (RSD) is a condition recently described by a group of sleep experts who developed diagnostic and polysomnographic criteria after conducting a comprehensive review of the available literature where poor sleep or restless sleep is a symptom alone or that accompanies other disorders. This group defined RSD as a condition characterized by parental complaints of frequent jerking movements during sleep, position changes, and sleep disruption that cause significant impairment during the day. Diagnostic criteria include the presence of symptoms for at least 3 months, 3 times a week, and at least 5 movements per hour on polysomnography. Changes in behavior during the day, such as drowsiness, irritability, and hyperactivity that are not explained by a medical, pharmacological, or behavioral condition, should be considered. Its estimated prevalence is 7.7% of children referred for sleep problems. Children often have ferritin levels below 50 µg/l, a point in common with restless legs syndrome. Treatment consists of iron supplements, which have shown benefits in these children. To establish the diagnosis, secondary symptoms of medical origin or other sleep disorders such as restless legs syndrome or periodic limb movement disorder must be ruled out. The objective of this report is to review the current recommendations on this entity, describe the clinical, pathophysiological, and polysomnographic keys, in order to highlight the need to publicize this condition and expand studies in age groups other than those already defined and to generate treatment guidelines.

[Abnormal nocturnal behavior mimicking REM sleep behavior disorder episodes in a patient with periodic limb movement disorder].

Periodic limb movement disorder (PLMD) is a condition in which patients experience frequent periodic limb movements of sleep (PLMS). Synchronized arousal responses cause sleep fragmentation, resulting in insomnia, daytime sleepiness, and fatigue. A 59-year-old man was identified as having intense sleep-talking and body movements, suggesting rapid eye movement (REM) sleep behavior disorder (RBD). Attended video-polysomnography (PSG) revealed that sleep-talking and body movements occurred only during non-REM sleep and were associated with PLMS-induced arousals (periodic leg movement arousal index, 53.2/h). Pramipexole administration improved events during sleep and daytime sleepiness, and the PSG findings and clinical course led to a diagnosis of PLMD. This case demonstrates that PLMD mimics the symptoms of RBD and that a detailed analysis of monitored video PSG is crucial to confirm the diagnosis of RBD and to identify or exclude other causes of sleep talking and behavior.

[Periodic limb movements in sleep and cerebral small vessel disease progression: a prospective cohort study]. / Periodicheskie dvizheniya konechnostei vo sne i progressirovanie tserebral'noi mikroangiopatii: prospektivnoe kogortnoe issledovanie.

OBJECTIVE: To determine the predictive role of periodic limb movements in sleep (PLMS) in cerebral small vessel disease (cSVD) progression rate. MATERIAL AND METHODS: Fifty patients with cSVD, aged 60-75 y.o., were enrolled. The study protocol included MRI assessment of white matter hyperintensities (WMH), nocturnal actigraphy and cognitive assessment. Depending on the PLMS, the main (PLM index ≥15) and the control (PLM index <15) groups were formed. The second visit was carried out in one year follow-up period, the examination consisted of brain MRI and cognitive assessment under the same protocol. ANCOVA was performed to determine if PLMS influence the degree of MRI- and neuropsychological changes. RESULTS: A significant effect of PLMS on the increase in the volume of WMH was revealed, both in the form of an increase in the index by more than 15 movements per hour (p=0.03), and quantitatively in the form of a connection with the index value (p=0.048). The influence of PLMS on the progression of cognitive dysfunction has not been found, however, it has been shown that the presence of PLMS is associated with lesions in the deep white matter (r=0.42, p<0.0001), and the results of neuropsychological tests are associated with lesions in the periventricular and juxtacortical WMH (p < 0.05 for each test). CONCLUSION: PLMS predict WMH progression in cSVD.

Time to rest a hypothesis? Accumulating evidence that periodic leg movements during sleep are not increased in children with attention-deficit hyperactivity disorder (ADHD): results of a case-control study and a meta-analysis.

STUDY OBJECTIVES: To address the hypothesis that periodic leg movements during sleep (PLMS) are more frequent in children with attention-deficit hyperactivity disorder (ADHD) when compared with typically developing (TD) children. To that end, we analyzed PLMS in a recent case-control study and conducted a systematic review and meta-analysis of PLMS frequency in children with ADHD and TD children. METHODS: In our case-control study, we compared the PLMS frequency of 24 children with ADHD (mean age 11 years, 17 males) to that of 22 age-matched typically developing (TD) children (mean age 10 years, 12 males). A subsequent meta-analysis included 33 studies that described PLMS frequency in groups of children with ADHD and/or groups of TD children. RESULTS: The case-control study did not show any differences in the frequency of PLMS between children with ADHD and TD children, a result that was consistent across a range of different definitions of PLMS, which in turn had a significant and systematic effect on PLMS frequency. The meta-analysis compared the average PLMS indices and the proportion of children with elevated PLMS indices between children with ADHD and TD children and across a number of analyses did not find any meta-analytic results that supported the hypothesis that PLMS are more frequent in children with ADHD. CONCLUSIONS: Our results suggest that PLMS are not more frequent in children with ADHD compared with TD children. A finding of frequent PLMS in a child with ADHD should therefore be considered a separate disorder and prompt specific diagnostic and therapeutic strategies.

Association between Self-Perceived Periodic Limb Movement during Sleep and Excessive Daytime Sleepiness Depend on Restless Leg Symptoms in Korean Adolescents.

Although periodic limb movement during sleep (PLMS) and restless legs syndrome (RLS) are common in children and adolescents, they are relatively overlooked as a target of treatment. PLMS has been evaluated as having a lower clinical significance than RLS. This study examined the relationship of socio-behavioral factors of PLMS in Korean adolescents and checked whether PLMS is associated with excessive daytime sleepiness (EDS), depending on whether restless legs symptoms accompany it. In a cross-sectional study, 25,789 adolescents between 12 and 18 years of age (15.76 ± 1.73 years; female 51.49%) were evaluated using an online survey. Various self-report questionnaires were used to assess PLMS and RLS symptoms, EDS, sleep habits, and various socio-behavioral factors. The prevalence of self-perceived PLMS and restless legs symptoms were 903 (3.50%) and 1311 (5.08%), respectively. Of the 1311 participants, 399 had self-perceived PLMS. The odds ratios (ORs) for self-perceived PLMS in participants with restless legs symptoms were: males (OR = 1.528; 95% CI: 1.145-2.040), usually/always experienced apnea apnea (OR, 3.006; 95% CI, 1.954-4.624), increased proneness to Internet addiction (OR = 1.013; 95% CI: 1.001-1.025), sometimes/often consuming coffee (OR = 1.312; 95% CI: 1.015-1.695), EDS (OR = 0.826; 95% CI: 0.488-1.398), and perceived insufficient sleep (OR = 1.143; 95% CI: 0.835-1.565). The male gender, witness apnea, consuming coffee, and being prone to Internet addiction were identified as factors significantly associated with self-perceived PLMS in participants with restless legs symptoms. However, EDS and insufficient sleep were associated with self-perceived PLMS in the absence of restless legs symptoms.

Large body movements on video polysomnography are associated with daytime dysfunction in children with restless sleep disorder.

Restless sleep disorder (RSD) is a newly defined sleep-related movement disorder characterized by large muscle movements (LMM) in sleep. We examined the sleep study, clinical characteristics, and daytime functioning in children with RSD and compared them to children with periodic limb movement disorder (PLMD) or restless legs syndrome (RLS). Video polysomnography from 47 children with restless sleep was retrospectively reviewed for LMM and age- and sex-matched to 34 children with PLMD and 12 children with RLS. Data examined included PSG characteristics, ferritin, Pediatric Quality of Life (PedsQL), and Epworth Sleepiness Scale (ESS). Fourteen children met the clinical criteria for RSD with an LMM index of 5 or more per hour of sleep. Mean ESS was elevated in patients with RSD compared to either the PLMD or RLS groups though the result did not reach statistical significance (RSD = 10.20 ± 6.81, PLMD = 6.19 ± 4.14, RLS = 6.25 ± 4.90). The PedsQL score was significantly decreased in the RLS group compared to RSD and was reduced overall in all three groups (PedsQL Total RSD = 70.76 ± 18.05, PLMD = 57.05 ± 20.33, RLS = 53.24 ± 16.97). Serum ferritin values were similar in all three groups (RSD = 26.89 ± 10.29, PLMD = 33.91 ± 20.31, RLS = 23.69 ± 12.94 ng/mL, p = ns). Children with RSD demonstrate increased daytime sleepiness compared to PLMD or RLS and all three disease groups showed decreased quality of life. Further studies are needed to examine long-term consequences of RSD.

Restless sleep disorder, restless legs syndrome, and periodic limb movement disorder-Sleep in motion!

Sleep-related movement disorders (SRMDs) represent an important part of pediatric sleep disorders. The most common complaint in SRMD is restless sleep at night. Restless sleep is reported in up to 80% of children with restless legs syndrome (RLS) and children with periodic limb movements of sleep (PLMS) disorder (PLMD). However, restless sleep causing daytime behavioral consequences can be seen in children without another apparent condition and has recently been identified as a new independent primary pediatric sleep disorder, called restless sleep disorder (RSD). This study describes these three main SRMDs (RSD, RLS, and PLMD), explains the new consensus criteria for RSD, emphasizes the rapidly evolving areas of research in this field, and proposes recommendations for future research. In particular, the published data constitute convincing evidence that sleep-related movements are disruptors of sleep quality and continuity. However, while important advancements have recently been reported in adults, a detailed analysis of the phenomenology and consequences of sleep-related movements has just started in children. New approaches, standardized diagnostic methods, and specific guidelines are needed in the field of pediatric SRMD.

Periodic Leg Movements During Sleep.

Periodic leg movements during sleep (PLMS) are a frequent finding in nocturnal sleep registrations that include tibialis anterior electromyographic signals. Different PLMS scoring rules exist and can have a major impact on PLMS frequency, which tends to be underappreciated. There is no consistent evidence that frequent PLMS are a causal risk factor for clinically significant outcomes. Several critical open questions are identified that need to be addressed, including but not limited to the consideration of the full range of all sleep-related leg movement activity.

Restless legs syndrome and periodic limb movements in 86 patients with multiple sclerosis.

STUDY OBJECTIVES: To assess the frequency of restless legs syndrome (RLS), periodic limb movements during sleep (PLMS), and their overlap in a large sample of patients with multiple sclerosis (MS). To compare clinical and paraclinical findings among four subgroups of patients: RLS-/PLMS- (patients without RLS and PLMS), RLS+/PLMS- (patients with RLS and without PLMS), RLS-/PLMS (patients without RLS and with PLMS), and RLS+/PLMS+ (patients with both RLS and PLMS). METHODS: In this cross-sectional, observational, instrumental study, 86 patients (M/F: 27/59; mean age 48.0 ± 10.8 years) with a diagnosis of MS underwent a telephone interview assessing the five standard diagnostic criteria for RLS. Seventy-six participants underwent polysomnography (PSG) and maintenance of wakefulness test (MWT). Instrumental and clinical findings were subsequently statistically compared to investigate their association with RLS and PLMS index (PLMSI). RESULTS: RLS and PLMS (PLMSI ≥15/h) frequency in patients with MS were of 31.4% and 31.6%, respectively. Among patients with RLS, 37.5% had a PLMSI of at least 15/h. RLS-/PLMS+ group showed higher wake after sleep onset (p = 0.01), stage shifts per hour (p = 0.03), increased stage N1 (p = 0.03), and reduction in stage N3 (p = 0.01) compared to RLS-/PLMS-. RLS had no influence on clinical and PSG parameters (p = 0.45). CONCLUSIONS: RLS is highly frequent in patients with MS. The frequency of PLMS is comparable to the general population. The low percentage of patients with RLS having a high PLMSI, together with the absence of correlation between RLS and female gender and older age, supports the existence of a distinct symptomatic form of RLS in MS.

Cyclic Alternating Pattern Analysis in Periodic Leg Movements in Sleep in Patients With Obstructive Sleep Apnea Syndrome Before and After Positive Airway Pressure Treatment.

PURPOSE: Cyclic alternating pattern (CAP) is known to increase in many conditions of sleep disruption and sleep disorders, including obstructive sleep apnea syndrome and periodic limb movements in sleep (PLMS). Periodic limb movements in sleep associated with obstructive sleep apnea syndrome may vanish after positive airway pressure treatment, may persist, or emerge at treatment night. Here, the authors aimed to investigate the underlying pathophysiology of nonvanishing, vanishing, or newly emergent PLMS. METHODS: The authors designed a prospective study and included 10 patients with nonvanishing PLMS during positive airway pressure therapy, 10 patients with vanishing PLMS, 10 patients with newly emergent PLMS, and 10 patients without PLMS at both nights. The CAP analysis was performed in detail at diagnostic polysomnography recording and at positive airway pressure titration. The changes in CAP parameters were evaluated in regard to nonvanishing, vanishing, or newly emergent PLMS. RESULTS: Periodic limb movements in sleep related to A1 subtype of CAP were observed to decrease under positive airway pressure titration more than PLMS related to A3 subtype of CAP. The A3 subtype of CAP was higher in patients with vanishing PLMS than those with newly emergent PLMS. The newly emergent PLMS were mostly related to A1 subtype of CAP compared with A3 subtype of CAP. CONCLUSIONS: This study showed that vanishing, nonvanishing, or newly emerging PLMS may indeed represent different underlying pathophysiology. The authors suggest that organization of sleep and preservation of ultradian rhythms during titration may determine whether PLMS will be vanished or persist. Newly emergent PLMS may probably arise from a separate central generator by the activation of higher cortical areas.

Effects of new PLM scoring rules on PLM rate in relation to sleep and resting wake for RLS and healthy controls.

PURPOSE: This study evaluates the differences in periodic leg movement (PLM) rates for Restless Legs Syndrome (RLS) and healthy controls when using the updated PLM scoring criteria developed by IRLSSG in 2016 versus the prior PLM scoring criteria developed by IRLSSG in 2006. Four major problems with the prior standards had been objectively identified, i.e. minimum inter-movement interval should be 10 not 5 s, non-PLM leg movements should end any preceding PLM sequence, a leg movement (LM) can be any length > 0.5 s, and a PLM should be a persisting movement not a couple or a series of closely spaced, very brief events. Each of these led to including, erroneously, various random leg movements as PLM. Correcting these problems was expected to increase specificity, reducing the number of PLM detected, particularly in situations producing relatively more random leg movements, e.g. wake vs. sleep and controls without PLMD vs. RLS patients. METHODS: This study evaluated the putative benefits of the updated, 2016-scoring criteria. The LMs from 42 RLS patients and 30 age- and gender-matched controls were scored for PLMS and PLMW from standard all-night PSG recordings using both 2006 and 2016 WASM criteria. RESULTS/CONCLUSION: The results confirmed that that the 2016 compared to the 2006 criteria generally decreased the PLM rates with particularly large decreases for the conditions with more random non-PLM events, e.g. wake times and normal healthy controls. This supported the view that the new criteria succeeded in increasing the specificity of PLM detection. Moreover, the changes in PLM rates were generally small for the conditions with relatively few random LM, e.g. RLS and sleep. Thus the bulk of existing PLMS research does not require reconsideration of results, with possible exception of special situations with relatively more random leg movements than periodic leg movements, e.g. wake, healthy normals and children.