Search

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.

To examine how changes in sleep patterns and sleep problems occurring between the pre-pandemic and the Covid-19 lockdown period influenced mood-behavioral functioning of children with Attention Deficit Hyperactivity Disorder (ADHD).Parents of 992 children with ADHD (85.4% boys, mean age: 11.52 years, SD = 3.17), recruited from the Italian ADHD family association, completed a modified version of the Sleep Disturbance Scale for Children and filled out 11 emotional behavioral items selected from the Child Behavior Checklist (CBCL) 6-18 questionnaire. Subgroups identified based on sleep duration changes ("maintained", "increased", "reduced") and of sleep problems during lockdown ("onset", "remission", "maintained", "no sleep problem") were analyzed to evaluate the association with internalizing and externalizing scores.Sleep duration showed no or low influence on internalizing and externalizing behaviors after control for age, sex, and socioeconomic status. Patients with ADHD with "no sleep problem" showed significant lower scores in internalizing and externalizing behaviors than those who "maintained" or had "onset" of different sleep problems. The effect sizes were higher for internalizing than externalizing behaviors. Lower internalizing scores were found in those who remitted difficulty in falling asleep, daytime sleepiness, nightmares, vs. the "maintained" or "onset" groups and those who remitted hypnic jerks vs. the "onset" group. Children with ADHD who "maintained" sleep terrors reported higher internalizing and mainly externalizing scores than the other groups.Sleep problems negatively influence daytime functioning of patients with ADHD. but mood and behavioral domains show different susceptibility to the changes of sleep problems, and different vulnerability to specific sleep problems.

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.

Abnormalities in cortical sources of resting-state eyes closed electroencephalographic (rsEEG) rhythms recorded by hospital settings (10-20 montage) with 19 scalp electrodes characterized Alzheimer's disease (AD) from preclinical to dementia stages. An intriguing rsEEG application is the monitoring and evaluation of AD progression in large populations with few electrodes in low-cost devices. Here we evaluated whether the above-mentioned abnormalities can be observed from fewer scalp electrodes in patients with mild cognitive impairment due to AD (ADMCI). Clinical and rsEEG data acquired in hospital settings (10-20 montage) from 75 ADMCI participants and 70 age-, education-, and sex-matched normal elderly controls (Nold) were available in an Italian-Turkish archive (PDWAVES Consortium; www.pdwaves.eu ). Standard spectral fast fourier transform (FFT) analysis of rsEEG data for individual delta, theta, and alpha frequency bands was computed from 6 monopolar scalp electrodes to derive bipolar C3-P3, C4-P4, P3-O1, and P4-O2 markers. The ADMCI group showed increased delta and decreased alpha power density at the C3-P3, C4-P4, P3-O1, and P4-O2 bipolar channels compared to the Nold group. Increased theta power density for ADMCI patients was observed only at the C3-P3 bipolar channel. Best classification accuracy between the ADMCI and Nold individuals reached 81% (area under the receiver operating characteristic curve) using Alpha2/Theta power density computed at the C3-P3 bipolar channel. Standard rsEEG power density computed from six posterior bipolar channels characterized ADMCI status. These results may pave the way toward diffuse clinical applications in health monitoring of dementia using low-cost EEG systems with a strict number of electrodes in lower- and middle-income countries.

Study Objectives To investigate the frequency and characteristics of large muscle group movements (LMMs) during sleep in healthy adults. Methods LMMs were scored following the International Restless Legs Syndrome Study Group criteria in 100 healthy participants aged 19–77 years. A LMM was defined as a temporally overlapping increase in EMG activity and/or the occurrence of movement artifacts in at least two channels. LMM indices and durations in total sleep time (TST), NREM and REM sleep, and association with arousals, awakenings, and/or respiratory events were calculated. Correlations of LMMs indices and durations with sleep architecture, respiratory and motor events, and subjective sleep quality were investigated. Results Median LMMs index in TST was 6.8/h (interquartile range (IQR), 4.5–10.8/h), median mean duration 12.4 s (IQR 10.7–14.4 s). Mean LMMs duration was longer in NREM (median 12.7 s, IQR 11.1–15.2 s) versus REM sleep (median 10.3 s, IQR 8.0–13.5s), p Conclusions This is the first study providing normative data on LMMs frequency in healthy adults. LMMs are a ubiquitous phenomenon often associated with other events. Correlation with arousals and respiratory events suggests a potential clinical significance of LMMs in adults that awaits further investigation.

Alzheimer's disease dementia (ADD) is the most diffuse neurodegenerative disorder belonging to mild cognitive impairment (MCI) and dementia in old persons. This disease is provoked by an abnormal accumulation of amyloid-beta and tauopathy proteins in the brain. Very recently, the first disease-modifying drug has been licensed with reserve (i.e., Aducanumab). Therefore, there is a need to identify and use biomarkers probing the neurophysiological underpinnings of human cognitive functions to test the clinical efficacy of that drug. In this regard, event-related electroencephalographic potentials (ERPs) and oscillations (EROs) are promising candidates. Here, an Expert Panel from the Electrophysiology Professional Interest Area of the Alzheimer's Association and Global Brain Consortium reviewed the field literature on the effects of the most used symptomatic drug against ADD (i.e., Acetylcholinesterase inhibitors) on ERPs and EROs in ADD patients with MCI and dementia at the group level. The most convincing results were found in ADD patients. In those patients, Acetylcholinesterase inhibitors partially normalized ERP P300 peak latency and amplitude in oddball paradigms using visual stimuli. In these same paradigms, those drugs partially normalize ERO phase-locking at the theta band (4–7 Hz) and spectral coherence between electrode pairs at the gamma (around 40 Hz) band. These results are of great interest and may motivate multicentric, double-blind, randomized, and placebo-controlled clinical trials in MCI and ADD patients for final cross-validation. United States Department of Health & Human Services National Institutes of Health (NIH) - USA

Davide Sparasci,1 Francesco Fanfulla,2 Raffaele Ferri,3 Debora Aricò,3 Daniela Distefano,4 Emanuele Pravatà ,4 Raphael Heinzer,5 José Haba-Rubio,5 Mathieu Berger,5 Gianna Carla Riccitelli,6– 8 Claudio Gobbi,6,8 Chiara Zecca,6,8,* Mauro Manconi1,8,* 1Sleep Medicine Unit, Neurocenter of Southern Switzerland, Lugano, Switzerland; 2Sleep Medicine Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Scientific Institute of Pavia, Pavia, Italy; 3Sleep Research Centre; Department of Neurology I.C., Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Italy; 4Neuroradiology Clinic, Ospedale Regionale di Lugano, Neurocenter of Southern Switzerland, Lugano, Switzerland; 5Center for Investigation and Research in Sleep (CIRS), Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland; 6Multiple Sclerosis Center, Neurocenter of Southern Switzerland, Lugano, Switzerland; 7Neuropsychology and Behavioural Neurology Research Unit, Neurocenter of Southern Switzerland, Lugano, Switzerland; 8Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland*These authors contributed equally to this workCorrespondence: Raffaele Ferri, Sleep Research Centre; Department of Neurology I.C., Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Via Conte Ruggero 73, Troina, 94018, Italy, Email rferri@oasi.en.itBackground: Multiple sclerosis (MS) represents a risk factor for sleep disorders, but there are conflicting results about the prevalence and severity of sleep-related breathing disorders (SRBD) in MS. Most available data come from self-administered questionnaires.Objective: To conduct a polysomnographic study in MS focused on SRBD, compared to a group of healthy controls (HC), also considering the neuroimaging findings. To evaluate the impact of SRBD on vigilance, fatigue and depression in MS.Methods: In this cross-sectional, observational, instrumental study, 67 MS patients (men/women: 20/47; mean age: 50.6± 8.2 years) underwent PSG and maintenance of wakefulness test. Findings were compared to 67 age-, sex-, BMI-matched HC, by using parametric (Student’s t-test) and nonparametric statistics (chi-squared test). A subgroup analysis was then performed, evaluating the influence of brainstem (mesencephalic, pontine and medullary) lesions at neuroimaging on instrumental and clinical data: MS patients with at least one brainstem lesion vs MS patients without vs HC.Results: The frequency of SRBD was comparable in MS patients and HC. No MS patient had a central apnea index ≥ 2/h. The respiratory disturbance index (RDI) did not correlate to clinical parameters such as fatigue and depression. Patients with MS were drowsier than HC (47% vs 26%, p = 0.019) and showed a worse sleep pattern, in terms of duration, efficiency and architecture.Conclusion: Our study does not provide evidence of an association between MS-specific symptoms such as fatigue, sleepiness, depression and central or obstructive apneas, even in the presence of brainstem lesions.Keywords: sleep-related breathing disorders, multiple sclerosis, sleep quality, polysomnography

Coffee intake has been recently associated with better cognition and mood in mild vascular cognitive impairment (mVCI). As tobacco can reduce the caffeine half-life, we excluded smokers from the original sample. Hamilton Depression Rating Scale (HDRS), mini-mental state examination (MMSE), Stroop Colour-Word Interference Test (Stroop), activities of daily living (ADL0) and instrumental ADL were the outcome measures. Significant differences were observed in higher consumption groups (moderate intake for HDRS; high intake for MMSE and Stroop) compared to the other groups, as well as in age and education. With age, education and coffee used as independent predictors, and HDRS, Stroop and MMSE as dependent variables, a correlation was found between age and both MMSE and Stroop, as well as between education and MMSE and between HDRS and Stroop; coffee intake negatively correlated with HDRS and Stroop. Higher coffee consumption was associated with better psycho-cognitive status among non-smokers with mVCI.

Introduction Although very few prospective clinical trials are available assessing the benefits of drugs in isolated REM sleep behavior disorder (iRBD), clonazepam and melatonin are considered as the first-line treatment options. However, while evidence supporting the efficacy of these two compounds on the clinical behavioral outcomes seems to be clear, it is not clear if they are able to significantly modify the main polysomnographic (PSG) feature of iRBD, i.e. REM sleep without atonia (RSWA). For this reason, we carried-out an observational cross-sectional retrospective PSG study of the effects of clonazepam and melatonin on RSWA. Methods A total of 83 iRBD patients (70 males and 13 females, age range 50.9-83.2 years) were enrolled in this study: 43 drug-free, 21 patients taking at bedtime chronically (>6 months) clonazepam (0.5-2 mg), seven patients taking melatonin extended-release alone (2-3 mg), and 12 taking a combination of clonazepam and melatonin extended-release (same doses as above). PSG studies were assessed for all subjects, including the measurement of the automatic REM sleep atonia index (RAI) and periodic leg movements during sleep, as well as a series of demographic and clinical variables, such as age, age at onset, disease duration, clinical global impression scale (severity and improvement), mini-mental state evaluation, and RBD severity scale. Results None of the outcomes considered in this study showed significant differences between the groups considered. All showed low average values of RAI, as expected, and there were no differences between patients taking clonazepam, melatonin, or a combination of them (drug-free 0.778±0.184, clonazepam 0.797±0.183, clonazepam+melatonin 0.692±0.224, melatonin 0.673±0.228; ANOVA F = 1.329, p = 0.271), despite the clinical global impression scale-improvement was reported to be “much improved” or “minimally improved” in all treated patients. Conclusion This study confirms our previous findings in smaller patient series taking only clonazepam and suggest that both clonazepam and melatonin might be beneficial on some clinical manifestations of iRBD but are unable to modify its underlying neurophysiology. This might also indicate that these agents do not seem to interfere with the core mechanisms of this disease and other disease modifying drugs need to be discovered for iRBD. Support (if any)

STUDY OBJECTIVES: To carry out an analysis of leg movement activity during sleep in a polysomnography dataset of patients with multiple sclerosis (MS) in comparison to idiopathic restless legs syndrome (iRLS) and healthy controls. METHODS: In this cross-sectional, observational, instrumental study, 57 patients (males/females: 11/46; mean age 46.2 ± 10.2 years) with a diagnosis of MS underwent a telephone interview assessing the 5 standard diagnostic criteria for RLS and polysomnography. Sleep architecture and leg movement activity during sleep were subsequently compared: 1) 40 patients with MS without RLS (MS–RLS) vs 28 healthy controls; 2) 17 patients with MS with RLS (MS+RLS) vs 35 patients with iRLS; 3) MS+RLS vs MS–RLS. RESULTS: MS–RLS and MS+RLS presented increased sleep latency, percentage of sleep stage N1, and reduced total sleep time compared to healthy controls and iRLS, respectively. The periodic limb movements during sleep (PLMS) index was higher in MS–RLS than in healthy controls (P = .035) and lower in MS+RLS compared to iRLS (P = .024). PLMS in MS+RLS were less periodic, less often bilateral, and with shorter single movements compared to the typical PLMS in iRLS. CONCLUSIONS: MS is a risk factor for RLS, PLMS, and for a lower sleep quality in comparison to healthy patients. PLMS in MS+RLS are fewer and shorter if compared to iRLS. Our results suggest a dissociation between motor (PLMS) and sensory symptoms (RLS sensory component) in RLS secondary to MS, with possible treatment implications. CITATION: Ferri R, Sparasci D, Castelnovo A, et al. Leg movement activity during sleep in multiple sclerosis with and without restless legs syndrome. J Clin Sleep Med. 2022;18(1):11–20.

Parkinson’s disease (PD) is a neurodegenerative synucleinopathy that has a not yet fully understood molecular pathomechanism behind it. The role of risk genes regulated by small non-coding RNAs, or microRNAs (miRNAs), has also been highlighted in PD, where they may influence disease progression and comorbidities. In this case-control study, we analyzed miRNAs on peripheral blood mononuclear cells by means of RNA-seq in 30 participants, with the aim of identifying miRNAs differentially expressed in PD compared to age-matched healthy controls. Additionally, we investigated the pathways influenced by differentially expressed miRNAs and assessed whether a specific pathway could potentially be associated with PD susceptibility (enrichment analyses performed using the Ingenuity Pathway Analysis tools). Overall, considering that the upregulation of miRNAs might be related with the downregulation of their messenger RNA targets, and vice versa, we found several putative targets of dysregulated miRNAs (i.e., upregulated: hsa-miR-1275, hsa-miR-23a-5p, hsa-miR-432-5p, hsa-miR-4433b-3p, and hsa-miR-4443; downregulated: hsa-miR-142-5p, hsa-miR-143-3p, hsa-miR-374a-3p, hsa-miR-542-3p, and hsa-miR-99a-5p). An inverse connection between cancer and neurodegeneration, called “inverse comorbidity”, has also been noted, showing that some genes or miRNAs may be expressed oppositely in neurodegenerative disorders and in some cancers. Therefore, it may be reasonable to consider these miRNAs as potential diagnostic markers and outcome measures.

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.

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.

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.

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.

STUDY OBJECTIVES: The current study examined the impact of home confinement (lockdown) because of the COVID-19 pandemic on the sleep patterns of children and adolescents with attention-deficit hyperactivity disorder (ADHD). METHODS: Nine hundred ninety-two parents of children and adolescents with ADHD filled out an anonymous online survey through the ADHD family association website. The survey investigated the sleep patterns and disturbances (using a modified version of the Sleep Disturbance Scale for Children) and screen exposure time before and during lockdown. RESULTS: During lockdown, 59.3% of children and 69.4% of adolescents with ADHD reported a change of bedtime, with a significant increase in patients with ADHD who went to sleep at 11 pm or later. Sleep duration, in contrast, resulted in 2 opposing processes with more children and adolescents sleeping either less than 6 hours/night or 10–11 hours/night. Among children and adolescents, respectively, 19.9% and 22% slept less than they did before lockdown, whereas 21.4% and 27.4% slept for more hours. Bedtime delay and decreased sleep duration were associated with an increase in screen time exposure. Moreover, patients with ADHD reported an increase in sleep disturbances when compared to their previous condition, mainly including difficulties falling asleep, anxiety at bedtime, night awakenings, nightmares, and daytime sleepiness. CONCLUSIONS: Lockdown impacted sleep-wake rhythms by strengthening the maladaptive sleep patterns reported in usual-life conditions in children and adolescents with ADHD. CITATION: Bruni O, Giallonardo M, Sacco R, Ferri R, Melegari MG. The impact of lockdown on sleep patterns of children and adolescents with ADHD. J Clin Sleep Med. 2021;17(9):1759–1765.

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.

Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterised by an urge to move the limbs with a circadian pattern (occurring in the evening/at night), more prominent at rest, and relieved with movements. RLS is one of the most prevalent sleep disorders, occurring in 5%-10% of the European population. Thomas Willis first described RLS clinical cases already in the 17th century, and Karl-Axel Ekbom described the disease as a modern clinical entity in the 20th century. Despite variable severity, RLS can markedly affect sleep (partly through the presence of periodic leg movements) and quality of life, with a relevant socio-economic impact. Thus, its recognition and treatment are essential. However, screening methods present limitations and should be improved. Moreover, available RLS treatment options albeit providing sustained relief to many patients are limited in number. Additionally, the development of augmentation with dopamine agonists represents a major treatment problem. A better understanding of RLS pathomechanisms can bring to light novel treatment possibilities. With emerging new avenues of research in pharmacology, imaging, genetics, and animal models of RLS, this is an interesting and constantly growing field of research. This review will update the reader on the current state of RLS clinical practice and research, with a special focus on the contribution of European researchers.

Introduction Children with history of prematurity are at higher risk of complications, comorbidities and iron deficiency, including restless legs syndrome and periodic limb movements of sleep (PLMS). In this study we assess the prevalence of restless sleep disorder and PLMS in children with history of prematurity. Methods Retrospective chart review of sleep studies in children aged 1-18 years, with history of prematurity, from July 2021 to July 2022 at Seattle Children's Hospital. Only diagnostic studies in children without diagnosis of a genetic syndrome or airway surgery were included. Results During the study, 2,577 sleep studies were conducted, 162 were in children with history of prematurity (6%): 25 were split or titration studies (14%), 29 children had syndromes (Down, Prader Willi, Wiedmann Beckmann, Achondroplasia), 4 tracheostomy studies, 6 in infants aged < 12 months and 6 were post airway intervention. Ninety-two diagnostic studies were included in analysis. Median birth age was 31 weeks, interquartile range (IQR) 27-34 weeks. Thirty-two (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring; 18% had PLMS index >5/hour, 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters between the children with RSD, PLMS and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p=0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5), or than in the nonRSD/nonPLMS group (median 2.0, IQR 0.8-4.5). Altogether, children with RSD and those with PLMS had restless sleep as an indication for the sleep study in 70% of cases while snoring was the indication in only 26.7% of them. Conclusion We have previously reported that in the Seattle Children's Hospital Sleep Center the prevalence of RSD is 7.7% and that of PLMS is 9.3%; in this new analysis we found a higher frequency of RSD and elevated PLMS in children with history of prematurity. Premature children are higher risk of iron deficiency, among other complications and comorbidities. These new results confirm the previous reports of increased PLMS and add new knowledge on the prevalence of RSD in these children Support (if any)

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.

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.

Repetitive transcranial magnetic stimulation (rTMS) is a widely used non-invasive neuromodulatory technique. When applied in sleep medicine, the main hypothesis explaining its effects concerns the modulation of synaptic plasticity and the strength of connections between the brain areas involved in sleep disorders. Recently, there has been a significant increase in the publication of rTMS studies in primary sleep disorders. A multi-database-based search converges on the evidence that rTMS is safe and feasible in chronic insomnia, obstructive sleep apnea syndrome (OSAS), restless legs syndrome (RLS), and sleep deprivation-related cognitive deficits, whereas limited or no data are available for narcolepsy, sleep bruxism, and REM sleep behavior disorder. Regarding efficacy, the stimulation of the dorsolateral prefrontal cortex bilaterally, right parietal cortex, and dominant primary motor cortex (M1) in insomnia, as well as the stimulation of M1 leg area bilaterally, left primary somatosensory cortex, and left M1 in RLS reduced subjective symptoms and severity scale scores, with effects lasting for up to weeks; conversely, no relevant effect was observed in OSAS and narcolepsy. Nevertheless, several limitations especially regarding the stimulation protocols need to be considered. This review should be viewed as a step towards the further contribution of individually tailored neuromodulatory techniques for sleep disorders.

Background: Patients with amnesic mild cognitive impairment due to Alzheimer’s disease (ADMCI) typically show a “slowing” of cortical resting-state eyes-closed electroencephalographic (rsEEG) rhythms. Some of them also show subclinical, non-convulsive, and epileptiform EEG activity (EEA) with an unclear relationship with that “slowing.” Objective: Here we tested the hypothesis that the “slowing” of rsEEG rhythms is related to EEA in ADMCI patients. Methods: Clinical and instrumental datasets in 62 ADMCI patients and 38 normal elderly (Nold) subjects were available in a national archive. No participant had received a clinical diagnosis of epilepsy. The eLORETA freeware estimated rsEEG cortical sources. The area under the receiver operating characteristic curve (AUROCC) indexed the accuracy of eLORETA solutions in the classification between ADMCI-EEA and ADMCI-noEEA individuals. Results: EEA was observed in 15% (N = 8) of the ADMCI patients. The ADMCI-EEA group showed: 1) more abnormal Aβ42 levels in the cerebrospinal fluid as compared to the ADMCI-noEEA group and 2) higher temporal and occipital delta (

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.

Cerebrospinal and structural-molecular neuroimaging in-vivo biomarkers are recommended for diagnostic purposes in Alzheimer’s disease (AD) and other dementias; however, they do not explain the effects of AD neuropathology on neurophysiological mechanisms underpinning cognitive processes. Here, an Expert Panel from the Electrophysiology Professional Interest Area of the Alzheimer’s Association reviewed the field literature and reached consensus on the event-related electroencephalographic oscillations (EROs) that show consistent abnormalities in patients with significant cognitive deficits due to Alzheimer’s, Parkinson’s (PD), Lewy body (LBD), and cerebrovascular diseases. Converging evidence from oddball paradigms showed that, as compared to cognitively unimpaired (CU) older adults, AD patients had lower amplitude in widespread delta (>4 Hz) and theta (4–7 Hz) phase-locked EROs as a function of disease severity. Similar effects were also observed in PD, LBD, and/or cerebrovascular cognitive impairment patients. Non-phase-locked alpha (8–12 Hz) and beta (13–30 Hz) oscillations were abnormally reduced (event-related desynchronization, ERD) in AD patients relative to CU. However, studies on patients with other dementias remain lacking. Delta and theta phase-locked EROs during oddball tasks may be useful neurophysiological biomarkers of cognitive systems at work in heuristic and intervention clinical trials performed in AD patients, but more research is needed regarding their potential role for other dementias. European Committee (H2020-EU.1.3.1.H2020-MSCA-ITN-ETN-2016 project)

The auditory mismatch negativity, a component of the event-related potential elicited by an unexpected stimulus in a sequence of acoustic stimuli, provides an objective measure of the accuracy of the echoic information processing of the human brain in vivo. Auditory mismatch negativity is also a useful probe of cortical glutamatergic N-methyl-d-aspartate receptor activity and disturbance. Notably, auditory mismatch negativity is consistently impaired in schizophrenia. Because of the wide spectrum extending from bipolar affective illness and schizoaffective psychosis to typical schizophrenia, we examined the literature on auditory mismatch negativity in bipolar disorder with the aim to find any neurophysiological dysfunction concerning pre-attentive information processing shared by these clinical conditions. This focused review includes 26 original articles published in peer-reviewed journals and indexed in the National Institutes of Health National Library of Medicine (PubMed) search system. Overall, evidence is consistent with the finding that auditory mismatch negativity is impaired in bipolar disorder with psychotic features, even though to a lesser extent than in schizophrenia. It must be acknowledged that, in a few twin and family studies, mismatch negativity abnormalities were not specifically associated with bipolar disorder. In conclusion, auditory mismatch negativity research supports the involvement of the N-methyl-d-aspartate system in the pathophysiology of bipolar disorder, as previously assessed for schizophrenia, thus creating an intriguing trait d’union between these two mental illnesses and stimulating the development of novel therapeutic agents. With additional replication and validation, auditory mismatch negativity may be further considered as a correlate of a common psychopathology of schizophrenia and bipolar spectrum illnesses.

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.

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.