Restless sleep disorder in children with epileptic and non-epileptic nocturnal attacks.

Restless sleep disorder (RSD) is an important sleep disorder characterised by the presence of frequent large muscle movements (LMM) during sleep, which may be comorbid to other conditions/diseases. In this study, we investigated the frequency and the characteristics of RSD among children who were evaluated by polysomnography (PSG) due to epileptic and non-epileptic nocturnal attacks. We analysed consecutively children younger than 18 years who were referred for PSG recording due to abnormal motor activities during sleep. The diagnosis of nocturnal events as sleep-related epilepsy was made based on the current consensus. Patients who were referred with suspicion of sleep-related epilepsy, but who were diagnosed to have non-epileptic nocturnal events and children with a definitive diagnosis of NREM sleep parasomnias were also enrolled. Sixty-two children were analysed in this study (17 children with sleep-related epilepsy, 20 children with NREM parasomnia, and 25 children with nocturnal events not otherwise classified [neNOS]). The mean number of LMM, LMM index, LMM-associated with arousal and its index were all significantly higher in children with sleep-related epilepsy. Restless sleep disorder was present in 47.1% of patients with epilepsy, 25% of patients with parasomnia, and in 20% of patients with neNOS. The mean A3 duration and the A3 index were higher in children with sleep-related epilepsy and RSD compared with those with parasomnia and restless sleep disorder. Patients with RSD had lower ferritin levels than those without RSD in all subgroups. Our study demonstrates a high prevalence of restless sleep disorder in children with sleep-related epilepsy, associated with an increased cyclic alternating pattern.

Restless sleep disorder in a sample of children and adolescents with autism spectrum disorder: preliminary results from a case series.

STUDY OBJECTIVES: Sleep disorders are a frequent comorbidity among children with autism spectrum disorder (ASD). Among sleep-related issues of ASD, restless sleep is a common complaint. In recent years, restless sleep disorder (RSD) has been proposed as a new clinical entity, characterized by agitated sleep as its predominant manifestation. Despite the high prevalence of sleep disorders and data reporting restless sleep among ASD patients, to date no study has yet characterized RSD within patients with ASD. Therefore, the aim of our study was to assess the occurrence of RSD in a sample of children and adolescents with ASD through clinical and polysomnographic assessment. METHODS: Children and adolescents with ASD ages 6-18 years were recruited for the study. Through parental interviews, patients with a suspected RSD were selected and offered diagnostic investigation by video-polysomnography and blood tests to assess martial balance. RESULTS: Among the 129 participants included, 16 patients (12.4%) were found to have a suspected RSD. Only 6 (4.7%) underwent video-polysomnography due to lack of compliance or family refusal. In 6/6 participants examined, the disorder was confirmed by video-polysomnography movement analysis (total movement index ≥ 5 events/h) and ferritin values were found in the normal range. CONCLUSIONS: RSD does not appear to be particularly frequent among patients with ASD and that of iron metabolism may not be the main factor implicated in the pathogenesis of RSD within this population. Additional evaluation is needed to confirm the result and further investigate the etiological mechanisms underlying the disorder. CITATION: Voci A, Mazzone L, De Stefano D, Valeriani M, Bruni O, Moavero R. Restless sleep disorder in a sample of children and adolescents with autism spectrum disorder: preliminary results from a case series. J Clin Sleep Med. 2024;20(3):427-432.

Objective and Subjective Sleep Patterns in Adults With Maturity-Onset Diabetes of the Young (MODY).

OBJECTIVE: To examine sleep patterns in adults with maturity-onset diabetes of the young (MODY). RESEARCH DESIGN AND METHODS: Adults with glucokinase (GCK)-MODY and transcription factor (TF)-related MODY (HNF1A, HNF1B, HNF4A) were recruited (n = 24; age 46.0 years, 79% women, BMI 24.7 kg/m2) from The University of Chicago's Monogenic Diabetes Registry. Sleep patterns were assessed by 2-week wrist actigraphy (total 315 nights), one night of a home sleep apnea test, and validated surveys. RESULTS: Overall, compared with established criteria, 29% of participants had sleep latency ≥15 min, 38% had sleep efficiency ≤85%, 46% had wake after sleep onset >40 min, all indicating poor objective sleep quality. Among all participants, 54% had a sleep duration below the recommended minimum of 7 h, 88% reported poor sleep quality, 58% had obstructive sleep apnea, and 71% reported insomnia. Compared with GCK-MODY, participants with TF-related MODY had poorer objective sleep quality and increased night-to-night variability in sleep patterns. CONCLUSIONS: Sleep disturbances appear to be common in adults with MODY despite absent traditional risk factors for sleep disorders. Future research investigating the sleep-diabetes relationship is warranted in this population.

Multidimensional phenotyping of the post-COVID-19 syndrome: A Swiss survey study.

INTRODUCTION: Post-COVID-19 syndrome affects approximately 10-25% of people after a COVID-19 infection, irrespective of initial COVID-19 severity. The aim of this project was to assess the clinical characteristics, course, and prognosis of post-COVID-19 syndrome using a systematic multidimensional approach. PATIENTS AND METHODS: An online survey of people with suspected and confirmed COVID-19 and post-COVID-19 syndrome, distributed via Swiss COVID-19 support groups, social media, and our post-COVID-19 consultation, was performed. A total of 8 post-infectious domains were assessed with 120 questions. Data were collected from October 15 to December 12, 2021, and 309 participants were included. Analysis of clinical phenomenology of post-COVID-19 syndrome was performed using comparative statistics. RESULTS: The three most prevalent post-COVID-19 symptoms in our survey cohort were fatigue (288/309, 93.2%), pain including headache (218/309, 70.6%), and sleep-wake disturbances (mainly insomnia and excessive daytime sleepiness, 145/309, 46.9%). Post-COVID-19 syndrome had an impact on work ability, as more than half of the respondents (168/268, 62.7%) reported an inability to work, which lasted on average 26.6 weeks (95% CI 23.5-29.6, range 1-94, n = 168). Quality of life measured by WHO-5 Well-being Index was overall low in respondents with post-COVID-19 syndrome (mean, 95% CI 9.1 [8.5-9.8], range 1-25, n = 239). CONCLUSION: Fatigue, pain, and sleep-wake disturbances were the main symptoms of the post-COVID-19 syndrome in our cohort and had an impact on the quality of life and ability to work in a majority of patients. However, survey respondents reported a significant reduction in symptoms over 12 months. Post-COVID-19 syndrome remains a significant challenge. Further studies to characterize this syndrome and to explore therapeutic options are therefore urgently needed.

Restless Sleep Disorder (RSD): a New Sleep Disorder in Children. A Rapid Review.

PURPOSE OF REVIEW: Restless sleep disorder (RSD) is a recently identified pediatric sleep disorder characterized by frequent movements during sleep associated with daytime symptoms. In this review we summarize the expanding evidence of the clinical presentation of RSD, potential pathophysiology, associated comorbidities, and current treatment options that will help the pediatrician identify children with RSD in a timely manner. RECENT FINDINGS: RSD is diagnosed in 7.7% of children referred evaluated in a pediatric sleep center. Children with RSD present with frequent nightly movements during sleep for at least 3 months, and have daytime symptoms related to poor sleep quality including excessive sleepiness, hyperactivity, irritability among other symptoms. Current evidence shows an increased sympathetic predominance, increased NREM sleep instability, and iron deficiency, as well as increased prevalence in parasomnias and attention deficit hyperactivity disorder. Consensus diagnostic criteria were recently published to diagnose RSD and emergent evidence suggests that iron supplementation improves its nighttime and daytime 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.

The Evolving Nexus of Sleep and Depression.

Sleep disturbances and depression are closely linked and share a bidirectional relationship. These interconnections can inform the pathophysiology underlying each condition. Insomnia is an established and modifiable risk factor for depression, the treatment of which offers the critical opportunity to prevent major depressive episodes, a paradigm-shifting model for psychiatry. Identification of occult sleep disorders may also improve outcomes in treatment-resistant depression. Sleep alterations and manipulations may additionally clarify the mechanisms that underlie rapid-acting antidepressant therapies. Both sleep disturbance and depression are heterogeneous processes, and evolving standards in psychiatric research that consider the transdiagnostic components of each are more likely to lead to translational progress at their nexus. Emerging tools to objectively quantify sleep and its disturbances in the home environment offer great potential to advance clinical care and research, but nascent technologies require further advances and validation prior to widespread application at the interface of sleep and depression.

Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder.

The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin's effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.

Poor Sleep Quality Is Associated with Altered Taste Perception in Chinese Adults.

BACKGROUND: Small clinical studies have suggested that individuals with insufficient sleep could experience taste dysfunction. However, this notion has not been examined in a large-scale, population-based study. OBJECTIVE: This study aimed to examine whether overall sleep quality, as assessed by insomnia, daytime sleepiness, snoring, and sleep duration, was associated with the odds of having altered taste perception in a large population-based study. DESIGN: This was a cross-sectional study that used data from a subcohort of the Kailuan study, an ongoing multicenter cohort study that began in 2006 in Tangshan City, China. PARTICIPANTS/SETTING: The participants were 11,030 adults aged 25 years or older (mean age 53.7 ± 10.7 years), who were free of neurodegenerative diseases. All the participants had undergone questionnaire assessments and medical examinations at Kailuan General Hospital from June 2012 to October 2013. MAIN OUTCOME MEASURES: Altered taste and olfactory perception were assessed via a questionnaire with two questions regarding whether participants had any problems with sense of taste or smell for ≥3 months. STATISTICAL ANALYSES PERFORMED: The association between sleep quality and altered taste/olfactory perception was examined using a logistic regression model, adjusting for age, sex, lifestyle factors (eg, obesity, smoking, alcohol intake, and physical activity) and health status (eg, lipid profiles, blood pressure, modification use, and presence of chronic diseases). RESULTS: Poor overall sleep quality was associated with a higher risk of having altered taste perception (adjusted odds ratio for low vs high sleep quality 2.03, 95% CI 1.42 to 2.91; P < 0.001). Specifically, insomnia, daytime sleepiness, and short sleep duration, but not prolonged sleep duration and snoring, were significantly associated with altered taste perception. A significant association between overall sleep quality and the risk of having altered olfactory perception was also observed (adjusted odds ratio for low vs high sleep quality 2.17, 95% CI 1.68 to 2.80; P < 0.001). CONCLUSIONS: In this population-based study, poor sleep quality was associated with a high likelihood of altered taste perception.

The characterization of psychotic symptoms in succinic semialdehyde dehydrogenase deficiency: a review.

Succinic semialdehyde dehydrogenase (SSADH) deficiency is an ultra-rare inborn error of metabolism that results in disrupted gamma-amino butyric acid (GABA) catabolism. In addition to developmental delay, intellectual disability, hypotonia, ataxia, and seizures, a variety of neuropsychiatric symptoms may occur, including psychosis. By highlighting all available and relevant case reports/series, this qualitative review seeks to characterize the prevalence, clinical manifestation, pathophysiology, and treatment of psychotic symptoms in this population. Psychosis occurs in a minority of SSADH-deficient individuals, and most commonly presents as auditory or visual hallucinations with an onset in adolescence or young adulthood. Although the pathophysiology underlying the development of psychosis in this context is not fully understood, it likely in part relates to increased GABA and/or gamma hydroxybutyric acid activity. Although antipsychotic medications should be used cautiously in SSADH deficiency, they may be effective at treating emergent psychotic symptoms.

Tracking Sleep to Optimize Health.

With the advent of wearable biometric technology like smart watches, "hacking" our bodies' functions and cycles has become a tool in the never-ending quest for better health. And sleep is no exception. For example, a staggering one-third of Americans don't get enough sleep, according to the Centers for Disease Control and Prevention (CDC).

Sleep disorders in anti-NMDAR encephalitis.

OBJECTIVE: To describe the sleep disorders in anti-NMDA receptor encephalitis (anti-NMDARe). METHODS: Patients recovering from anti-NMDARe were invited to participate in a prospective observational single-center study including comprehensive clinical, video-polysomnography (V-PSG) sleep assessment, and neuropsychological evaluation. Age- and sex-matched healthy participants served as controls. RESULTS: Eighteen patients (89% female, median age 26 years, interquartile range [IQR] 21-29 years) and 21 controls (81% female, median age 23 years, IQR 18-26 years) were included. In the acute stage, 16 (89%) patients reported insomnia and 2 hypersomnia; nightmares occurred in 7. After the acute stage, 14 (78%) had hypersomnia. At study admission (median 183 days after disease onset, IQR 110-242 days), 8 patients still had hypersomnia, 1 had insomnia, and 9 had normal sleep duration. Patients had more daytime sleepiness than controls (higher Barcelona Sleepiness Index, p = 0.02, and Epworth Sleepiness Score, p = 0.04). On V-PSG, sleep efficiency was similar in both groups, but patients more frequently had multiple and longer confusional arousals in non-REM (NREM) sleep (videos provided). In addition, 13 (72%) patients had cognitive deficits; 12 (67%) had psychological, social, or occupational disability; and 33% had depression or mania. Compared with controls, patients had a higher body mass index (median 23.5 [IQR 22.3-30.2] vs 20.5 [19.1-21.1] kg/m2; p = 0.007). Between disease onset and last follow-up, 14 (78%) patients developed hyperphagia, and 6 (33%) developed hypersexuality (2 requiring hospitalization), all associated with sleep dysfunction. CONCLUSIONS: Sleep disturbances are frequent in anti-NMDARe. They show a temporal pattern (predominantly insomnia at onset; hypersomnia during recovery), are associated with behavioral and cognitive changes, and can occur with confusional arousals during NREM sleep.

Risk factors for sleep quality disturbances in patients with lumbar spinal stenosis before operation.

PURPOSE: We aimed to explore the risk factors of preoperative sleep quality in patients with lumbar spinal stenosis (LSS) and the association of sleep-related beliefs with sleep quality in these patients. METHODS: Sleep quality and related risk factors of sleep quality disturbances in patients with LSS preoperatively were assessed by questionnaires. Pittsburgh Sleep Quality Index (PSQI) for sleep quality, Oswestry Disability Index (ODI) for clinical outcomes, Visual Analog Scale for Pain (VAS Pain), Self-Rating Anxiety Scale (SAS) for anxiety level, and Dysfunctional Beliefs and Attitudes about Sleep (DBAS-16) for sleep-related beliefs were assessed. Bivariate logistic regression analysis was used to assess the risk factors of sleep quality disturbances. RESULTS: A total of 227 patients were enrolled, mean age 64 years (SD 13.1), 119 women (52%). The incidence of sleep quality disturbances in patients was 37% (83/227). Increased DBAS-16 scores (OR = 0.781; 95% CI, 0.725-0.841; p < 0.001) significantly decreased the probability of developing sleep quality disturbances, while increased anxiety levels (OR = 1.241; 95% CI, 1.152-1.337; p < 0.001) significantly increased the probability of developing sleep quality disturbances in patients. Factors including educational level, increased age, sex, preoperative length of stay, VAS Pain scores, and ODI scores showed no significant association and were therefore excluded from the model. CONCLUSIONS: High levels of anxiety and mistaken sleep-related beliefs were risk factors of sleep quality disturbances in patients with LSS before surgery. The more mistaken sleep-related beliefs were, the greater the probability of sleep disturbances.

Daytime sleep state misperception in a tertiary sleep centre population.

STUDY OBJECTIVES: Sleep state misperception is common in various sleep disorders, especially in chronic insomnia with a prevalence ranging between 9-50%. Most prior studies used nocturnal polysomnography (PSG) for the identification of sleep state misperception during nighttime. Our objective was to assess sleep state misperception during daytime in people with sleep disorders with excessive daytime sleepiness (EDS). METHODS: In this prospective observational study, we assessed the occurrence of, and factors influencing sleep state misperception in consecutive patients undergoing a routine multiple sleep latency test (MSLT) in a tertiary sleep-wake centre included between 2014 and 2017. Mixed models were applied to assess the influence of patients' clinical data on sleep state perception. RESULTS: People with narcolepsy type 1 (NT1, n = 33) and type 2 (NT2, n = 14), idiopathic hypersomnia (IH, n = 56), obstructive sleep apnea (OSA, n = 31) and insufficient sleep syndrome (ISS, n = 31) were included. The prevalence of both classical and reverse sleep state misperception did not differ between the sleep disorders (mean 25%, range 8-37%) after correction for sleep stage, sleep onset latency and age. Longer sleep onset latency and reaching only non-rapid eye movement (REM) sleep stage 1 were significant predictors for classical sleep state misperception. CONCLUSIONS: Sleep state misperception is common in people with NT1 and NT2, IH, OSA, and ISS. Classical sleep state misperception is more frequent in patients with longer sleep onset latencies who only reach non-REM sleep stage 1 during a nap.

Sleep and respiratory outcomes in neonates with Pierre Robin sequence: a concise review.

There are no standardized management algorithms for neonates with Pierre Robin sequence. Currently available literature is variable in terms of outcomes assessed across studies. In this paper, we have aimed to summarize the currently available literature on longitudinal sleep and respiratory outcomes in Pierre Robin sequence neonates with a focus on identifying gaps in literature and areas for future research development.

Pediatric polysomnography-A review of indications, technical aspects, and interpretation.

Polysomnography is an elaborate diagnostic test composed of numerous data-collecting sensors working concomitantly to aid in the evaluation of varied sleep disorders in all age groups. Polysomnography is the study of choice for the assessment of pediatric sleep-disordered breathing, including obstructive sleep apnea syndrome, central apnea, and hypoventilation disorders, and is used to help determine treatment efficacy. Beyond the purview of snoring and breathing pauses, polysomnography can elucidate the etiology of hypersomnolence, when associated with a multiple sleep latency test, and abnormal movements or events, whether nocturnal seizure or complex parasomnia, when a thorough patient history cannot provide clear answers. This review will highlight the multitudinous indications for pediatric polysomnography and detail its technical aspects by describing the multiple neurophysiologic and respiratory parametric sources. Knowledge of these technical aspects will provide the practitioner with a thoughtful means to understand the limitations and interpretation of polysomnography.

Hyper-serotonergic state determines onset and progression of idiopathic Parkinson's disease.

Despite decades of research on Parkinson's disease (PD), the etiology of this disease remains unclear. The present manuscript introduces a new hypothesis proposing a hyper-serotonergic state as the main mechanism leading to axonal impairment both in dopaminergic and serotonergic neurons in PD. The strong serotonergic connection between the raphe nuclei and the dorsal raphe nuclei with the basal ganglia, all important brain structures associated with the pathophysiology of PD, emphasize a potential role for this neurotransmitter in PD. Importantly, a hyper-serotonergic state can lead to axonal growth impairment, an effect that seems to be selective to axons that can respond to this neurotransmitter. Serotonin seems to be a promising candidate to explain several of the poorly understood early symptoms of PD, including sleep impairment, anxiety, altered gastrointestinal motility and hallucinations. The hypothesis proposed here emphasizes that a hyper-serotonergic state would initially cause disruption of axonal transportation, an acute state in which axonal changes are reversible and the neurodegenerative process can be halted. As the hyper-serotonergic state persists, the accumulation of neurotoxic products and a sustained impairment in axonal transportation would lead to axonal death and culminate in an irreversible neurodegenerative process. The potential implications of this hypothesis are discussed, as well as how future research can be employed to further elucidate the role of serotonin on PD progression.