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To evaluate the effects of bupropion on periodic limb movements during sleep (PLMS) and chin electromyography tone in children taking it for their mood disorder, compared to the effects of selective serotonin reuptake inhibitors (SSRIs) and of bupropion combined with SSRIs.Six adolescents (aged 16.0 ± 0.63 years) taking bupropion alone and 6 adolescents (aged 15.9 ± 1.36 years) taking bupropion in combination with an SSRI antidepressant were recruited, along with 10 adolescents (aged 16.2 ± 0.2 years) taking different SSRIs, and they were also enrolled together with 17 age- and sex-matched control patients (aged 15.5 ± 1.26 years). Polysomnographic studies were obtained, and participants' leg movement activity during sleep and muscle tone were assessed quantitatively (atonia index) during all sleep stages.Participants taking SSRIs showed PLMS indices significantly higher than those of control patients, whereas adolescents taking bupropion showed only slightly increased indexes of nonperiodic leg movements during sleep. No differences in PLMS were observed between adolescents taking bupropion alone or in association with SSRIs. The atonia index showed, within each sleep stage, the lowest values in the 2 groups taking SSRIs and the highest in the control patients; adolescents taking bupropion alone tended to show values slightly smaller than those of the control patients.We found that similar to adults, in adolescents SSRIs but not bupropion are associated with increased PLMS. Bupropion also seems to counteract the SSRI-induced increase of PLMS, when administered in combination; thus, the dopaminergic effect of bupropion seems to outmatch the antidopaminergic action of SSRIs. Conversely, bupropion does not counteract the effects of SSRIs on chin electromyography tone.DelRosso LM, Mogavero MP, Fickensher A, Bruni O, Schenck CH, Ferri R. Effects of bupropion and SSRI antidepressants on leg movement activity and chin muscle tone during sleep in adolescents.

Introduction Children with Down Syndrome (DS) are at high risk of sleep disordered breathing (SDB). We aimed to examine the burden of SDB in infants with DS referred to tertiary sleep center. Methods Infants (≤12 months old) with DS who underwent consecutive polysomnography (PSG) at a single academic sleep center over a 6-year period were included. OSA (obstructive apnea hypopnea index [oAHI]>1/hr), central sleep apnea (central apnea index>5/hr) and the presence of hypoventilation (% time spent with CO2 > 50 mmHg either by end-tidal or transcutaneous> 25% of total sleep time) and hypoxemia (time spent with O2 saturation 5 min) were ascertained. For infants who underwent adenotonsillectomy (AT), we compared the SDB metrics before and after the AT. Results A total of 40 infants were included (Mean age 6.6 months, male 66%). PSGs consisted of diagnostic (n=13) and split night (n=27, 68%) studies. All met criteria for OSA with mean oAHI 34.6 (32.3). Central sleep apnea was present in 11 (27.5%) of infants. A total of 11 (27.5%) had hypoxemia. Hypoventilation was present in 10 (25%) infants. There was a trend of association between hypothyroidism and hypoventilation (OR: 5.5 [0.96-34.4], p=0.056). Among 13 infants who underwent AT and had a follow up PSG, severity of OSA markedly reduced after AT (oAHI difference: 34/hr [29], p=0.0002). Conclusion This study highlights the high prevalence of SDB in infants with DS and supports early PSG assessment in this patient population.

After a detailed description of orexins and their roles in sleep and other medical disorders, we discuss here the current clinical evidence on the effects of dual (DORAs) or selective (SORAs) orexin receptor antagonists on insomnia with the aim to provide recommendations for their further assessment in a context of personalized and precision medicine. In the last decade, many trials have been conducted with orexin receptor antagonists, which represent an innovative and valid therapeutic option based on the multiple mechanisms of action of orexins on different biological circuits, both centrally and peripherally, and their role in a wide range of medical conditions which are often associated with insomnia. A very interesting aspect of this new category of drugs is that they have limited abuse liability and their discontinuation does not seem associated with significant rebound effects. Further studies on the efficacy of DORAs are required, especially on children and adolescents and in particular conditions, such as menopause. Which DORA is most suitable for each patient, based on comorbidities and/or concomitant treatments, should be the focus of further careful research. On the contrary, studies on SORAs, some of which seem to be appropriate also in insomnia in patients with psychiatric diseases, are still at an early stage and, therefore, do not allow to draw definite conclusions.

To test the hypothesis that children taking trazodone have less leg movements during sleep (LMS) and higher rapid eye movement (REM) sleep atonia than children taking selective serotonin reuptake inhibitors (SSRIs) but more than normal controls.Fifteen children (9 girls and 6 boys, mean age 11.7 years, standard deviation [SD] 3.42) taking trazodone (median dosage 50 mg/d, range 25-200 mg) for insomnia and 19 children (11 girls and 8 boys, mean age 13.7 years, SD 3.07) taking SSRIs for depression, anxiety, or both were consecutively recruited, as well as an age- and sex-matched group of 25 control children (17 girls and 8 boys, mean age 13.7 years, SD 3.11). LMS were scored and a series of parameters was calculated, along with the analysis of their time structure. The Atonia Index was then computed for each non-REM sleep stage and for REM sleep.Children taking trazodone exhibited slightly higher leg movement indices than controls but lower than those found in children taking SSRIs and their time structure was different. Chin electromyogram atonia in all sleep stages was not significantly altered in children taking trazodone but was decreased in children taking SSRIs, especially during non-REM sleep.In children, SSRIs but not trazodone are associated with a significantly increased number of LMS, including periodic LMS, and increased chin tone in all sleep stages. The assessment of periodic limb movement disorder and REM sleep without atonia might not be accurate when children are taking SSRIs because of their significant impact.DelRosso LM, Mogavero MP, Bruni O, Schenck CH, Fickenscher A, Ferri R. Trazodone affects periodic leg movements and chin muscle tone during sleep less than selective serotonin reuptake inhibitor antidepressants in children.

The vagal nerve stimulator (VNS) is a nonpharmacological treatment for refractory epilepsy. A side effect of the VNS is sleep-disordered breathing. The purpose of this study was to demonstrate how a surface electrode placed over the VNS lead can help distinguish whether sleep-disordered breathing is due to VNS discharge.Seven pediatric patients (aged 7.7 ± 2.2 years) with a VNS underwent a polysomnogram with an additional surface electrode on the left anterolateral neck to detect VNS discharge. The VNS-associated apnea-hypopnea index was calculated by determining the number of hypopneas and apneas occurring during VNS discharge. We evaluated the veracity of the VNS electrode by comparing signal duration and total number to those expected by programmed settings. We compared these findings to chin electromyogram signal change.Three patients had an obstructive pattern with VNS discharge, and 3 had an increase in respiratory rate without gas exchange abnormalities, including 1 with both patterns; 1 patient experienced no respiratory abnormalities. The mean obstructive apnea-hypopnea index was 8.2 ± 8.3 events/h. The mean VNS-associated apnea-hypopnea index was 4.8 ± 6.2 events/h and accounted for 46.9 ± 30.2% of the total obstructive apnea-hypopnea index. The additional electrode captured a statistically high percentage of expected discharges (94.7 ± 6.5%) compared to chin electromyogram (36.1 ± 35.8%;We demonstrated that a surface electrode on the VNS lead can temporally coregister VNS discharges and enabled us to attribute sleep-disordered breathing to VNS stimulation in 4 patients. We propose that this sensor be standard procedure in patients with VNS undergoing polysomnogram.Chan JHM, DelRosso LM, Ruth C, Wrede JE. A surface electrode adjacent to vagal nerve stimulator lead can aid in characterizing vagal nerve stimulator-mediated pediatric sleep-disordered breathing: a case series of 7 patients.

Sleep problems are common and often increase when initiating pharmacotherapy for ADHD. Stimulants are commonly associated with delayed sleep onset/insomnia although nonstimulants can be associated with daytime sleepiness. There is a wide variability in severity and duration of sleep effects, but most effects are mild and improve over time. Although sleep problems occur in all age groups, preschoolers and adolescents appear to be more vulnerable to adverse effects on sleep than adults and children. Interventions to improve sleep include behavioral therapy, changing dose schedules or formulations, and adding a sleep-promoting agent such as melatonin.

STUDY OBJECTIVES: Monitoring electrocardiogram is an integral component of pediatric polysomnography (PSG). There are limited data regarding arrhythmia and conduction disturbances in the pediatric population undergoing a PSG. In this work we present abnormal electrocardiogram findings during PSG in our sleep center. METHODS: A retrospective chart review from children who underwent PSG read by a single sleep medicine physician in the last year was carried out. Findings in children without cardiac disease and with first or second degree atrioventricular block were compared to those from children with premature ventricular contractions. RESULTS: A total of 1,235 PSGs were included. Twenty-four children (9 girls and 15 boys) aged 2–17 years (median 9 years) were identified with arrhythmias or conduction disturbances (1.9%). Nineteen out of 24 of these children (79.2%) had obstructive apnea-hypopnea index > 1 event/h; this frequency was not significantly different from that found in the whole group of 1,235 children. No statistically significant difference was found between children with atrioventricular block or premature ventricular contractions. Seven out of 9 children with atrioventricular block and 7 out of 10 with premature ventricular contractions had obstructive apnea-hypopnea index > 1 event/h, while 8 children with atrioventricular block out of 9 and 4 out of 10 with premature ventricular contractions were males (Fisher’s exact test P = .04). None of the children were found to have a structural or conduction abnormality when referred to cardiology. CONCLUSIONS: Our study supports that electrocardiogram abnormalities are rare in PSGs of children and not associated with cardiac disease or sleep disorders but appear more commonly in males. CITATION: Amin A, Mogavero MP, Ferri R, DelRosso LM. Incidental electrocardiogram abnormalities in children undergoing polysomnography. J Clin Sleep Med. 2021;17(12):2393–2398.

Sleep disturbances including bedtime problems and night awakenings are common during infancy. Polysomnography during the first years of life is performed mainly to rule out sleep-disordered breathing; however, sleep-related movement disorders can constitute a significant contributor to sleep disruption in this age group. Almost no studies have investigated the presence of periodic limb movements during sleep and underlying iron deficiency in infants, especially in those born preterm or with an underlying genetic syndrome. In this retrospective study we included infants 3-24 months referred for polysomnography for snoring or frequent nocturnal awakenings. All children had bloodwork (ferritin and haemoglobin) conducted within 3 months of the overnight sleep study. We studied 79 infants, including 31 (39.2%) full-term without diagnosis, 10 (12.7%) born premature, 16 (20.3%) with Down syndrome, 15 (19.0%) with Prader-Willi syndrome, and the remaining seven (8.9%) had various disorders. Compared with those with Down syndrome, Prader-Willi syndrome and full-term infants, those with prematurity showed a statistically significant elevated periodic limb movement index and lower ferritin levels than the other groups. Both ferritin (r = -0.18) and haemoglobin (r = -0.30) were negatively correlated with periodic limb movement index; however, this correlation reached statistical significance only for haemoglobin. Iron deficiency is associated with increased periodic leg movements during sleep in infants. Infants with prematurity had higher periodic limb movement index and lower ferritin levels than infants with Down syndrome, Prader-Willi syndrome or without diagnosis.

Iron supplementation is the most commonly considered treatment option for children with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD); however, there is a scarcity of evidence on the effectiveness of intravenous preparations. In this study, we evaluated the effectiveness and tolerability of intravenous ferric carboxymaltose (IV FCM) on clinical symptoms and iron indices in children with RLS or PLMD.This was a single-center retrospective data analysis. Children with a diagnosis of RLS or PLMD, who underwent a single infusion of IV FCM, were included. Clinical Global Impression (CGI) Scale scores, serum ferritin, and serum iron profile at baseline and after eight weeks post infusion were obtained. Adverse effects were assessed.Thirty-nine children received IV FCM, 29 with RLS and 10 with PLMD. Pre-infusion CGI-Severity revealed moderate illness, with post-infusion CGI-Improvement between "very much improved" and "much improved". Ferritin increased from 14.6 μg/L±7.01 to 112.4 μg/L±65.86 (p 0.00001), together with improvements in iron, total iron binding capacity, and transferrin levels from baseline to post-treatment. When compared to children with RLS, those with PLMD had a similar improvement in clinical symptoms and laboratory parameters. Seven subjects (14.3%) experienced one or two adverse events; all were mild.Children with RLS and PLMD responded to IV iron supplementation with improvement in both clinical severity and laboratory parameters. Treatment was well tolerated. Although larger, randomized-controlled trials are needed, IV FCM appears to be a promising alternative to oral iron supplementation for the treatment of pediatric RLS or PLMD.

Clinical neurophysiology studies can contribute important information about the physiology of human movement and the pathophysiology and diagnosis of different movement disorders. Some techniques can be accomplished in a routine clinical neurophysiology laboratory and others require some special equipment. This review, initiating a series of articles on this topic, focuses on the methods and techniques. The methods reviewed include EMG, EEG, MEG, evoked potentials, coherence, accelerometry, coherence, posturography (balance), gait, and sleep studies. Functional MRI (fMRI) is also reviewed as a physiological method that can be used independently or together with other methods. A few applications to patients with movement disorders are discussed as examples, but the detailed applications will be the subject of other articles.

Objective To analyze and identify differences in sleep spindles in children with restless sleep disorder (RSD), restless legs syndrome (RLS) and normal controls. Methods PSG (polysomnography) from children with RSD, RLS and normal controls were analyzed. Sleep spindle activity was detected on one frontal and one central electrode, for each epoch of N2 and N3 sleep. Sleep spindle density, duration and intensity (density × duration) were then obtained and used for analysis. Results Thirty-eight children with RSD, twenty-three children with RLS and twenty-nine controls were included. The duration of frontal spindles in sleep stage N2 was longer in children with RSD than in controls. Frontal spindle density and intensity tended to be increased in RSD children. No significant differences were found for central spindles. Conclusion Children with RSD had longer frontal spindles. This finding may contribute to explain the occurrence of excessive movement activity during sleep and the presence of daytime symptoms. Significance Recent research has demonstrated that children with RSD have increased NREM instability and sympathetic activation during sleep. Analyzing sleep spindles in children with RSD in comparison with children with RLS and controls adds to our understanding of the pathophysiology or RSD and its effects on daytime impairment.

Sleep medicine is a relatively young field with exponential growth in development and research in the last decades. Parallel to the advances in the United States, Latin America also had its beginnings in sleep medicine housed in neuroscience laboratories. Since the very first Latin American meeting in 1985, and the first sleep society in 1993, sleep research has undergone significant development in subsequent years. From contributions in animal research that allowed understanding of the activity of the brain during sleep to the studies that improved our knowledge of sleep disorders in humans, Latin America has become a scientific hub for expansion of sleep research. In this article, we present a historical account of the development of sleep medicine in Latin America, the current state of education and the achievements in research throughout history, and the latest advances in the trending areas of sleep science and medicine. These findings were presented during World Sleep Society meeting in Vancouver in 2019 and complement the work on sleep societies and training published by Vizcarra-Escobar et al in their article “Sleep societies and sleep training programs in Latin America” (J Clin Sleep Med. 2020;16(6):983–988). CITATION: Pedemonte M, Brockmann PE, DelRosso LM, Andersen ML. Past, present, and future of sleep medicine research in Latin America. J Clin Sleep Med. 2021;17(5):1133–1139.

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.

Restless sleep is a common complaint in children with sleep and other disorders, when it occurs as an isolated symptom it can depict a separate condition called restless sleep disorder (RSD). A key diagnostic feature of RSD is the polysomnographic (PSG) scoring of five or more large muscle movements (LMM) per hour of sleep. Initial publications on RSD used video-PSG (vPSG) analysis to count LMM. However, recently, scoring criteria for LMM on PSG signals alone have been published, but their correlation with vPSG scoring has not been done. In this study we compare vPSG to PSG scoring of LMM in a group of children with restless sleep.Video-PSG studies from 20 children (14 boys and six girls, mean age 11.3 years, SD 4.17) were reviewed by a blinded scorer. First, scorer used a video analysis (video-LMM), then on a different day the scorer used PSG criteria for LMM without video (PSG-LMM).PSG-LMM were found to be significantly more numerous than video-LMM (mean LMM index 8.6 ± 2.95 SD vs. 6.9 ± 2.40 SD, respectively) while their duration was not statistically different (mean LMM duration 11.6 ± 2.33 s vs. 11.6 ± 2.99 s, respectively). 95.4% of video-LMM were also detected by PSG. Both LMM indexes and durations obtained by the two methods correlated significantly between them. A cut off of 6.24 LMM/hour by PSG-LMM was calculated to be equivalent to 5 LMM by video-LMM.PSG-LMM scoring criteria detects95% of LLM scored by video-PSG. PSG-LMM lead to the detection of a higher number of movements, indicating their higher sensitivity in picking up LMM in PSG recording. This further supports that these criteria need adequate consideration for their eventual inclusion into the current sleep scoring manual. A higher index may be needed to diagnose RSD.

The objectives of this review and meta-analysis of polysomnographic data are those to focus on the clinical use of clonazepam for the management of sleep disorders by re-analyzing clinical trials and randomized clinical trials which have been published in peer-reviewed journals.A review of the literature including clinical trials and randomized controlled trials was performed in PubMed®, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. A random effects model meta-analysis was then carried out for the four more frequently reported polysomnographic measures: total sleep time, sleep latency, sleep efficiency, and periodic leg movement during sleep (PLMS) index.A total of 33 articles were retrieved and screened in full text, of which 18 met the criteria for review; among the latter, nine met the criteria for meta-analysis. The studies included in the review involved patients with insomnia, REM sleep behavior disorder, sleep bruxism, and restless leg syndrome or PLMS which reported, most often, an increase in total sleep time with clonazepam. A clear sleep-promoting effect of clonazepam was found also by meta-analysis.Our results indicate that the pharmacological treatment of sleep disorders with clonazepam must always be personalized according to the type of patient, the risk of addiction and the concomitant presence of respiratory disorders are key factors to take into account. However, in light of the clinical evidence of the few studies in the literature on the different types of disorders, more studies on the use of clonazepam (also in association with first choice treatments) are definitely needed.

Parasomnias usually present in childhood and resolve spontaneously. The diagnosis of non-rapid eye movement-related parasomnias is mainly based on clinical descriptors and can be challenging. Rapid eye movement-related parasomnias may index an underlying psychiatric disorder. Even if benign, parasomnias can affect quality of life. Pediatricians and child psychiatrists should be familiarized with these sleep disorders and suggest adequate sleep hygiene, avoidance of sleep deprivation, and regular bedtimes even on weekends as the first step in management of these disorders. Clinicians should pursue the opportunity for tailoring treatments and consider referral to a sleep expert when indicated.

STUDY OBJECTIVES: Restless sleep disorder (RSD) has recently been characterized clinically and polysomnographically in children and differentiated from restless legs syndrome (RLS). Heart rate variability is a reliable method to quantify autonomic changes during sleep. The aim of this study was to characterize heart rate variability in children with RSD, RLS, and individuals without these disorders, with the hypothesis that children with RSD have a shift toward sympathetic predominance during sleep. METHODS: We analyzed polysomnographic recordings from 32 children who fulfilled RSD diagnostic criteria (19 boys and 13 girls), 32 children with RLS (20 boys and 12 girls), and 33 individuals without disorders (17 boys and 16 girls). Four electrocardiographic epochs were chosen, 1 for each stage, and were analyzed for automatic detection of R waves. Time domain and frequency domain heart rate variability parameters were obtained and analyzed. RESULTS: In terms of time domain, only the standard deviation of the average interval between successive R waves during stage N3 was slightly but significantly higher in patients with RSD than in patients with RLS. In terms of frequency domain, in patients with RSD, the very-low-frequency and low-frequency bands were increased (vs patients with RLS and individuals without disorders, respectively), whereas low-frequency/high-frequency ratio tended to be increased in both patients with RSD and with RLS. In rapid eye movement sleep, low-frequency/high-frequency ratio was increased in both patients with RSD and with RLS. The low-frequency/high-frequency ratio increased in patients with RLS during quiet wakefulness preceding sleep. CONCLUSIONS: Children with RSD have increased sympathetic activation during sleep, particularly N3 and rapid eye movement sleep, compared with individuals without disorders but, as expected, not during wakefulness. Differently, children with RLS have sympathetic activation during relaxed wakefulness preceding sleep and during sleep. CITATION: DelRosso LM, Bruni O, Ferri R. Heart rate variability during sleep in children and adolescents with restless sleep disorder: a comparison with restless legs syndrome and normal controls. J Clin Sleep Med. 2020;16(11):1883–1890.

Restless legs syndrome (RLS) may be underdiagnosed in children with autism spectrum disorder (ASD) due to difficulty expressing the symptoms in their own words. In addition, administration of oral iron may be particularly difficult in children with ASD.This was a retrospective, open-label case series of children with ASD, restless legs (RL) symptoms, and serum ferritin30 μg/L, who either had failed or did not tolerate oral iron, and were subsequently treated with intravenous (IV) ferric carboxymaltose (FCM). Patients received a single dose of IV FCM, 15 mg/kg up to a maximum dose of 750 mg. Data collected pre- and eight weeks post-infusion included presenting symptoms, serum ferritin, iron profile, and Clinical Global Impression Scale (CGI-Severity pre- and CGI-Improvement post-infusion). Adverse effects were assessed.Nineteen children, 4-11 years old (12 male, median age 6, interquartile range (IQR 4-11) were included. A definite RLS diagnosis was identified in 6 verbal children (31.6%). RL symptoms (designated probable RLS) in the 13 other children met all RLS diagnostic criteria except "improvement of symptoms with movement," which was not definitively determined. Baseline median values were: ferritin 10 μg/L (IQR 10-16), iron 66.5 μg/dL (IQR 57-96), TIBC 382 μg/dL (IQR 360-411) and transferrin saturation 19% (IQR 14-28). Median CGI-S was 4 (moderate symptoms) (IQR 3-4). At eight weeks after IV FCM, all measures were improved. Median ferritin was 68 μg/L (IQR 62.5-109, p 0.00045). Median CGI-I was 1 (very much improved) (IQR 1-2). All children meeting definite RLS criteria improved. Three children in the probable RLS group did not improve. Children meeting the full RLS criteria had lower baseline ferritin levels than those with a probable diagnosis (9 μg/L, IQR 9-10 vs. 13 μg/L, IQR 10-16, Mann-Whitney test p 0.045). Adverse effects included lightheadedness, gastrointestinal discomfort, fever, and headache among others.The majority of children (84.2%) with ASD, restless legs symptoms, and serum ferritin30 μg/L had clinical improvement and significantly better serum iron parameters after a single IV FCM infusion. Although larger, randomized trials are needed, IV FCM appears to be a promising treatment for this subset of children with ASD.

Sleep homeostasis is a complex neurobiologic phenomenon involving a number of molecular pathways, neurotransmitter release, synaptic activity, and factors modulating neural networks. Sleep plasticity allows for homeostatic optimization of neural networks and the replay-based consolidation of specific circuits, especially important for cognition, behavior, and information processing. Furthermore, research is currently moving from an essentially brain-focused to a more comprehensive view involving other systems, such as the immune system, hormonal status, and metabolic pathways. When dysfunctional, these systems contribute to sleep loss and fragmentation as well as to sleep need. In this chapter, the implications of neural plasticity and sleep homeostasis for the diagnosis and treatment of some major sleep disorders, such as insomnia and sleep deprivation, obstructive sleep apnea syndrome, restless legs syndrome, REM sleep behavior disorder, and narcolepsy are discussed in detail with their therapeutical implications. This chapter highlights that sleep is necessary for the maintenance of an optimal brain function and is sensitive to both genetic background and environmental enrichment. Even in pathologic conditions, sleep acts as a resilient plastic state that consolidates prior information and prioritizes network activity for efficient brain functioning.

(1) Background: Breathing is an essential function that requires both metabolic (or au-tomatic) and voluntary (behavioral) control during wakefulness but during sleep depends on metabolic control via peripheral and central chemoreceptors. Breathing during sleep disordered breathing also depends on the maturity of the neural centers and the strength of the respiratory muscles. We do not know if the response to apnea varies with age. (2) Methods: We measured the obstructive apneas and hypopneas during REM and NREM in polysomnography studies from children referred for snoring. Exclusion criteria: younger than 1 year of age, neuromuscular or syndrome comorbidity, oxygen or positive airway pressure, central apnea, and studies with loss of airflow sensors. (3) Results: Two-hundred-and-sixty-eight sleep studies were included. Mean age was 8.7 years (4.68 SD), range 1–18 years, 160 were male, and 108 were female. The 5th centile of apnea duration during NREM is above 8 s at all ages, with a tendency to increase in the oldest groups up to 10 s. During REM sleep, it shows a gradual increase from 6 s in the youngest children to 10 s in the oldest. (4) Conclusions: Apnea/hypopnea length increases with age in children and adolescents independently from sex or severity of OSA. Using adult criteria in teens seems to be accurate.

Background Although several studies have shown the involvement of specific structures of the central nervous system, the dopaminergic system, and iron metabolism in restless legs syndrome (RLS), the exact location and extent of its anatomical substrate is not yet known. The scope of this new study was to investigate the brain subcortical gray structures, by means of structural magnetic resonance imaging (MRI) studies, in RLS patients in order to assess the presence of any volume or shape abnormalities involving these structures. Methods Thirty-three normal controls (24 females and nine males) and 45 RLS patients (34 females and 11 males) were retrospectively recruited and underwent a 1.5 Tesla MRI study with two-dimensional T1 sequences in the sagittal plane. Post-processing was performed by means of the Functional Magnetic Resonance Imaging of the Brain Analysis Group Integrated Registration and Segmentation Tool (FIRST) software, and both volumetric and morphological analyses of the thalamus, caudate, putamen, globus pallidus, brainstem, hippocampus, and amygdala, bilaterally, were carried out. Results A statistically significant volumetric reduction in the left amygdala and left globus pallidus was found in subjects with RLS, as well as large surface morphological alterations affecting the amygdala bilaterally and other less widespread surface changes in both hippocampi, the right caudate, the left globus pallidus, and the left putamen. Conclusions These findings seem to indicate that the basic mechanisms of RLS might include a pathway involving not only the hypothalamus-spinal dopaminergic circuit (nucleus A11), but also pathways including the basal ganglia and structures that are part of the limbic system; moreover, structural alterations in RLS seem to concern the morphology as well as the volume of the above structures. The role of basal ganglia in the complex neurophysiological and neurochemical mechanism of RLS needs to carefully reconsidered.

Restless sleep disorder is (RSD) a condition characterized by frequent large movements during sleep associated with daytime impairment. RSD has been studied in children aged 6 to 18 years. Polysomnography is necessary for the diagnosis of RSD. The current diagnostic criteria include more than 5 large movements per hour of sleep documented by PSG. The pathophysiology is not known yet, but iron deficiency and sleep instability and increased sympathetic activation are suspected to play a role. Iron supplementation is the only treatment option studied so far.

Early-onset restless legs syndrome has a relatively high prevalence in pediatrics, is highly familial, and is often preceded by a diagnosis of periodic limb movement disorder or childhood insomnia. Diagnostic criteria are derived but not equal to those of the adult syndrome and are adapted according to children's age and linguistic competence. Diagnosis requires parents or caregivers to participate; video-polysomnographic nocturnal recording, although not mandatory, may help confirm dubious cases. The syndrome severely impacts children's sleep and cognitive-behavioral abilities. Iron supplementation is currently the most used and viable therapeutic option.

Sleep-related rhythmic movements disorder (SRRMD), typically considered a benign pediatric sleep disorder, comprise a group of movement disorders that occur predominantly early in childhood with an average age of onset of 9 months of age. Although it usually resolves spontaneously as the child ages, it can persist into adulthood. In this article, the authors review the identification, diagnosis, and management of SRRMD in children and adults.

Study Objectives To evaluate leg movements during sleep (LMS) in children taking serotonergic antidepressants, compared to those of children with restless legs syndrome (RLS) and controls, and to assess the time structure of intermovement intervals (IMI). Methods Twenty-three children (12 girls, mean age 14.1 years) on antidepressants and with a total LMS index ≥ 15/h, 21 drug-naïve RLS children (11 girls, mean age 13.6 years) also with total LMS index ≥ 15/h, and 35 control children (17 girls, mean age 14.3 years) were recruited. LMS were scored and a series of parameters was calculated, along with the analysis of their time structure. Results Children taking antidepressants showed higher total and periodic LMS (PLMS) indexes than both controls and RLS children, as well as higher short-interval and isolated LMS indexes than controls. LMS periodicity was highest in children on antidepressants. In children taking antidepressants, a well-defined PLMS IMI peak corresponding to approximately 10–60 s, with a maximum at approximately 20 s was present, which was much less evident in RLS patients and absent in controls. A progressive decrease of PLMS during the night and more frequent arousals were found in children on antidepressants and with RLS. Conclusions Children taking serotonergic antidepressants show higher periodicity LMS than children with RLS or controls and have a higher number of PLMS through the night. Antidepressant-associated PLMS in children seem to have features similar to PLMS of adults with RLS. Whether this is a marker of an increased risk to develop RLS later in life needs to be determined.

Simple Summary This narrative review first describes from several points of view the complex interrelationship between cancer and neurodegeneration, with special attention to the mechanisms that might underlie an inverse relationship between them. In particular, the mechanisms that might induce an imbalance between cell apoptotic and proliferative stimuli are discussed. Second, the review summarizes findings on orexins and their involvement in narcolepsy, neurodegenerative diseases, and cancer, starting from epidemiological data then addressing laboratory findings, animal models, and human clinical observational and interventional investigations. Important research efforts are warranted on these topics, as they might lead to novel therapeutic approaches to both neurodegenerative diseases and cancer. Abstract Conditions such as Alzheimer’s (AD) and Parkinson’s diseases (PD) are less prevalent in cancer survivors and, overall, cancer is less prevalent in subjects with these neurodegenerative disorders. This seems to suggest that a propensity towards one type of disease may decrease the risk of the other. In addition to epidemiologic data, there is also evidence of a complex biological interconnection, with genes, proteins, and pathways often showing opposite dysregulation in cancer and neurodegenerative diseases. In this narrative review, we focus on the possible role played by orexin signaling, which is altered in patients with narcolepsy type 1 and in those with AD and PD, and which has been linked to β-amyloid brain levels and inflammation in mouse models and to cancer in cell lines. Taken together, these lines of evidence depict a possible case of inverse comorbidity between cancer and neurodegenerative disorders, with a role played by orexins. These considerations suggest a therapeutic potential of orexin modulation in diverse pathologies such as narcolepsy, neurodegenerative disorders, and cancer.

This paper aims to review the limitations of the current classification of insomnia of early childhood and propose a new conceptual model allowing a better understanding of its pathophysiology. Our hypothesis is that chronic insomnia of childhood has different phenotypical expressions, associated to different pathophysiological mechanisms. Based on a long-lasting experience in evaluating a very large number of children with specific insomnia symptoms (nocturnal awakenings, difficulty in falling asleep, nocturnal restlessness, early morning awakenings) and on published data, we hypothesize that different phenotypes of insomnia might exist with different therapeutic implications. We describe three phenotypes of insomnia in early childhood: a) insomnia with motor restlessness; b) insomnia characterized without difficulties in falling asleep but with long-lasting early morning awakenings; c) insomnia with multiple night awakenings and falling asleep difficulty. This type of categorization might have important implications for treatment, based on the different hypothetical neurotransmitter dysfunctions. The early identification of a phenotype of insomnia might guide to specific behavioral and/or pharmacological interventions with the aim to prevent chronic insomnia.

The objective of this study was to describe in detail the heart rate changes accompanying short-interval leg movements during sleep, periodic leg movements during sleep, and isolated leg movements during sleep in children and adolescents with restless legs syndrome, and to compare them with the same findings in adults with restless legs syndrome. We analysed time series of R-R intervals synchronized to the onset of short-interval leg movements during sleep, periodic leg movements during sleep or isolated leg movements during sleep that entailed an arousal during non-rapid-eye-movement sleep. We assessed cardiac activation based on the heart rate changes with respect to baseline during non-rapid-eye-movement sleep without leg movements. All types of leg movements recorded during sleep were accompanied by important heart rate changes also in children, with an overall impact similar to that observed in adults. In all age groups, heart rate changes accompanying short-interval leg movements during sleep were constituted by a tachycardia, without a subsequent relative bradycardia, that was instead evident for periodic leg movements during sleep and isolated leg movements during sleep. Moreover, an age-related decline of the relative bradycardia following the heart rate increase, in association with periodic leg movements during sleep and isolated leg movements during sleep, was observed. Our findings show that important heart rate changes accompany all leg movements during sleep at all ages in restless legs syndrome, with significant age-related differences. This information represents an important contribution to the ongoing scientific debate on the possibility and opportunity to treat periodic leg movements during sleep.

Children with psychiatric comorbidities frequently are referred for evaluation of sleep complaints. Common sleep symptoms can include difficulty falling asleep, frequent nocturnal awakening, restless sleep, and symptoms of restless legs syndrome (RLS). The understanding of the sleep condition in relation to the psychiatric comorbidity often is a challenge to the physician and often sleep disorders remain undiagnosed, untreated, or undertreated. Restless legs syndrome has been associated with psychiatric comorbidities and with certain medications, such as antidepressants, antihistamines, and antipsychotics. This article reviews the presentation of RLS and restless sleep, the association with psychiatric comorbidities, and treatment options.

There is a gap in the manuals for scoring sleep-related movements because of the absence of rules for scoring large movements. A taskforce of the International Restless Legs Syndrome Study Group (IRLSSG) elaborated rules that define the detection and quantification of movements involving large muscle groups. Consensus on each of the criteria in this article was reached by testing the presence of consensus on a first proposal; if no consensus was achieved, the concerns were considered and used to modify the proposal. This process was iterated until consensus was reached. A preliminary analysis of the duration of movements involving large muscle groups was also carried out on data from two previous studies, which, however, used a visual analysis of video-polysomnographic (PSG) recordings obtained from children or adults. Technical specifications and scoring rules were designed for the detection and quantification of large muscle group movements during sleep with a duration between 3 and 45 seconds in adults or 3 and 30 seconds in children, characterized by an increase in electromyographic activity and/or the occurrence of movement artifact in any combination of at least two recommended channels and not meeting the criteria for any other type of movement. Large muscle group movements are often accompanied by sleep stage changes, arousals, awakenings, and heart rate rises. The absence of clear and detailed rules defining them has likely impeded the development of studies that might disclose their clinical relevance; these new rules fill this gap.