Origin, synchronization, and propagation of sleep slow waves in children.

STUDY OBJECTIVES: Sleep slow wave activity, as measured using EEG delta power (<4 Hz), undergoes significant changes throughout development, mirroring changes in brain function and anatomy. Yet, age-dependent variations in the characteristics of individual slow waves have not been thoroughly investigated. Here we aimed at characterizing individual slow wave properties such as origin, synchronization, and cortical propagation at the transition between childhood and adulthood. METHODS: We analyzed overnight high-density (256 electrodes) EEG recordings of healthy typically developing children (N = 21, 10.3 ± 1.5 years old) and young healthy adults (N = 18, 31.1 ± 4.4 years old). All recordings were preprocessed to reduce artifacts, and NREM slow waves were detected and characterized using validated algorithms. The threshold for statistical significance was set at p = 0.05. RESULTS: The slow waves of children were larger and steeper, but less widespread than those of adults. Moreover, they tended to mainly originate from and spread over more posterior brain areas. Relative to those of adults, the slow waves of children also displayed a tendency to more strongly involve and originate from the right than the left hemisphere. The separate analysis of slow waves characterized by high and low synchronization efficiency showed that these waves undergo partially distinct maturation patterns, consistent with their possible dependence on different generation and synchronization mechanisms. CONCLUSIONS: Changes in slow wave origin, synchronization, and propagation at the transition between childhood and adulthood are consistent with known modifications in cortico-cortical and subcortico-cortical brain connectivity. In this light, changes in slow-wave properties may provide a valuable yardstick to assess, track, and interpret physiological and pathological development.

Clinical and instrumental features in 82 patients with insufficient sleep syndrome.

Insufficient sleep syndrome possibly represents the worldwide leading cause of daytime sleepiness, but remains poorly recognised and studied. The aim of this case series is to comprehensively describe a cohort of patients with insufficient sleep syndrome. Eighty-two patients were studied concerning demographic and socio-economic features, medical, psychiatric and sleep comorbidities, substance use, sleep symptoms, actigraphy, video-polysomnography, multiple sleep latency tests and treatment. The typical patient with insufficient sleep syndrome is a middle-aged adult (with no difference of gender), employed, who has a family, often carrying psychiatric and neurological comorbidities, in particular headache, anxiety and depression. Other sleep disorders, especially mild sleep apnea and bruxism, were common as well. Actigraphy was a valuable tool in the characterisation of insufficient sleep syndrome, showing a sleep restriction during weekdays, associated with a recovery rebound of night sleep during weekends and a high amount of daytime sleep. An over- or underestimation of sleeping was common, concerning both the duration of night sleep and daytime napping. The average daily sleep considering both daytime and night-time, weekdays and weekends corresponds to the recommended minimal normal duration, meaning that the burden of insufficient sleep syndrome could mainly depend on sleep fragmentation and low quality. Sleep efficiency was elevated both in actigraphy and video-polysomnography. Multiple sleep latency tests evidenced a tendency toward sleep-onset rapid eye movement periods. Our study offers a comprehensive characterisation of patients with insufficient sleep syndrome, and clarifies their sleeping pattern, opening avenues for management and treatment of the disorder. Current options seem not adapted, and in our opinion a cognitive-behavioural psychotherapy protocol should be developed.

Sleep microstructure in attention deficit hyperactivity disorder according to the underlying sleep phenotypes.

The analysis of sleep microstructure in attention deficit hyperactivity disorder (ADHD) revealed an under-representation of the EEG slow component during NREM sleep. Previous studies either excluded or did not characterize objectively sleep disorders, which notoriously affect sleep architecture. The present study aimed to investigate the cyclic alternating pattern in a real clinical sample of children with ADHD, in whom sleep disorders could be considered. Twenty-seven consecutively enrolled drug-naïve children (mean age, 10.53 years; nine females) and 23 controls (mean age, 10.22 years; 11 females) underwent a full sleep investigation, including attended video-polysomnography. Visual cyclic alternating pattern analysis was performed in a blinded way. Children with ADHD had one or more sleep disorders (a narcolepsy-like phenotype was found in two cases, sleep onset insomnia in three cases, arousal disorder in one case, movement disorder phenotype in six cases and obstructive sleep apnea in 11 cases, and six children had sleep-related epileptiform discharges). Children with ADHD and normal controls showed a similar microstructure with a cyclic alternating pattern rate of about 50%. Children with obstructive sleep apnea had a significantly higher cyclic alternating pattern rate during stage N3. Despite not reaching statistical differences, a lower cyclic alternating pattern rate and A1 index were found in children without epileptic abnormalities/obstructive sleep apnea. Our analysis might allow differentiation of the "primary form" of ADHD associated with a decrease of NREM instability from those forms associated with sleep apnea and epileptic activity.

Behavioural and emotional profiles of children and adolescents with disorders of arousal.

Disorders of arousals are common sleep disorders characterized by complex motor behaviours that arise episodically out of slow-wave sleep. Psychological distress has long been associated with disorders of arousal, but this link remains controversial, especially in children and adolescents. The aim of this multi-centre study was to characterize behavioural and emotional problems in a sample of children/adolescents with disorders of arousal, and to explore their relationship with the severity of nocturnal episodes. The parents of 41 children/adolescents with a diagnosis of disorders of arousal (11.5 ± 3.3 years old, 61% males) and of a group of 41 age- and gender-matched control participants filled in the Child Behavior Checklist, along with the Sleep Disturbance Scale for Children and the Paris Arousal Disorders Severity Scale. Multilevel t-tests revealed significantly higher total scores and sub-scores of the Child Behavior Checklist for the patient group compared with the control group. Thirty-four percent of the patients obtained pathological total scores, and 12% of them borderline scores. The severity of emotional/behavioural problems in the patient group was positively correlated with the severity of the nocturnal episodes. Interestingly, children/adolescents with disorders of arousal also obtained higher excessive daytime sleepiness and insomnia symptoms sub-scores at the Sleep Disturbance Scale for Children. These results confirmed the hypothesis that behavioural/emotional problems are surprisingly common in children/adolescents with disorders of arousal. Further studies are warranted to investigate the causal relationship between pathological manifestations, subtler sleep abnormalities, and diurnal emotional/behavioural problems in children/adolescents with disorders of arousal.

The Swiss Primary Hypersomnolence and Narcolepsy Cohort study (SPHYNCS): Study protocol for a prospective, multicentre cohort observational study.

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH.

Contribution of sleep disturbances to fatigue in multiple sclerosis: a prospective study using clinical and polysomnographic parameters.

BACKGROUND AND PURPOSE: Fatigue is amongst the most frequent and disabling symptoms of multiple sclerosis and a close relation between fatigue and sleep quality has been hypothesized. In this study the contribution of sleep disturbances measured by clinical and polysomnographic parameters to fatigue in multiple sclerosis was investigated. METHODS: This was a prospective instrumental study performed at the Neurocenter of Southern Switzerland. Demographic data and clinical characteristics including fatigue (as measured by the modified fatigue impact scale [MFIS]), neurological disability, psychiatric symptoms, medications and sleep-related variables were collected at baseline visit and by a home full-night polysomnography. The associations between sleep-related variables and the MFIS were tested using partial correlations adjusted by demographic and sleep-unrelated clinical factors. RESULTS: Seventy-six patients were included in the study, of whom 53 (69.7%) had an MFIS ≥38 points (median 49.5, interquartile range 31.0-62.0). MFIS scores were positively associated with age, neurological disability, symptoms of depression and anxiety, and use of benzodiazepines and selective serotonin reuptake inhibitors. When adjusting for these variables, the presence of restless legs syndrome (RLS) (r = 0.37, p = 0.005) and periodic leg movements index (r = -0.33, p = 0.014) were associated with MFIS. Excessive daytime sleepiness, total sleep time, sleep efficiency, respiratory disturbances, and percentage of time spent in the different sleep stages (N1, N2, N3 and rapid eye movement) were not associated with fatigue. CONCLUSIONS: Multiple sclerosis patients with a diagnosis of RLS had significantly higher global fatigue scores compared to those without RLS. Future studies should investigate whether medical treatment of RLS can ameliorate fatigue.

From physiological neck myoclonus to sleep related head jerk.

Neck myoclonus (NM) is a frequent recently described sleep-related motor phenomenon occurring mainly during REM sleep with uncertain effect on sleep continuity. To better describe this phenomenon we studied 11 consecutive drug-free patients undergoing a video-polysomnographic (V-PSG) study who present at least 5 NM events in one single night of recording. All events were measured and checked for their association with rapid eye and leg movements, EEG arousals, awakenings and Bereitschaftspotential. One hundred and eighty-two motor events from 11 subjects were analyzed. Motor events were approximately 0.5 s in duration and occurred during REM sleep in 79.7% of the cases. Only 14.8% of the events were associated with rapid eye movements, 52.2% with leg movements, while approximately 80% of them were accompanied by an arousal or awakening. No EEG abnormalities and Bereitschaftspotential were observed. For its duration and its segregation in sleep, NM could be more appropriately named "sleep-related head jerks" (SRHJ). SRHJ should be recognized and its effect on sleep stability should be re-considered.

The role of sleep-related cognitive functions in the spectrum of benign epilepsy with centro-temporal spikes.

Heterogeneous cognitive deficits have been described in the spectrum of benign epilepsy with centro-temporal spikes, which strongly correlate with the intensity of interictal epileptiform discharges and its spreading, in particular during sleep, mostly within the perisylvian cognitive network. The aim of this review is to discuss current findings regarding the connection between sleep alterations and cognitive function in the spectrum of benign epilepsy with centro-temporal spikes. A longer sleep onset latency is the only evident sleep macrostructure alteration reported in the spectrum of benign epilepsy with centro-temporal spikes. On a microstructural level, a higher spike count of descending compared to ascending slopes of sleep cycles, an impairment of slow wave downscaling, and amplitude and slope of slow waves were found in the spectrum of benign epilepsy with centro-temporal spikes. Moreover, children with benign epilepsy with centro-temporal spikes had a reduced non-rapid eye movement sleep instability, in terms of cyclic alternating pattern, similar to that found in children with attention-deficit hyperactivity disorders and in children with obstructive sleep apnea and centro-temporal spike during sleep. Children with benign epilepsy with centro-temporal spikes have a known comorbidity with attention-deficit hyperactivity disorders and obstructive sleep apnea.Conclusion: Considering the common sleep microstructure alterations, the presence of attention deficit and hyperactivity and/or sleep apnea may be a considered warning sign in the case of benign epilepsy with centro-temporal spikes. What is Known: • Sleep related-cognitive deficits have been described in the spectrum of benign epilepsy with centro-temporal spikes. The degree of sleep alterations may predict the neurocognitive outcome, and help clinicians to choose the right treatment. What is New: • Considering the common sleep microstructure alterations, attention deficit and sleep apnea, may be a considered warning signs.

ERS statement on obstructive sleep disordered breathing in 1- to 23-month-old children.

The present statement was produced by a European Respiratory Society Task Force to summarise the evidence and current practice on the diagnosis and management of obstructive sleep disordered breathing (SDB) in children aged 1-23 months. A systematic literature search was completed and 159 articles were summarised to answer clinically relevant questions. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are identified. Morbidity (pulmonary hypertension, growth delay, behavioural problems) and coexisting conditions (feeding difficulties, recurrent otitis media) may be present. SDB severity is measured objectively, preferably by polysomnography, or alternatively polygraphy or nocturnal oximetry. Children with apparent upper airway obstruction during wakefulness, those with abnormal sleep study in combination with SDB symptoms (e.g. snoring) and/or conditions predisposing to SDB (e.g. mandibular hypoplasia) as well as children with SDB and complex conditions (e.g. Down syndrome, Prader-Willi syndrome) will benefit from treatment. Adenotonsillectomy and continuous positive airway pressure are the most frequently used treatment measures along with interventions targeting specific conditions (e.g. supraglottoplasty for laryngomalacia or nasopharyngeal airway for mandibular hypoplasia). Hence, obstructive SDB in children aged 1-23 months is a multifactorial disorder that requires objective assessment and treatment of all underlying abnormalities that contribute to upper airway obstruction during sleep.

Obstructive sleep disordered breathing in 2- to 18-year-old children: diagnosis and management.

This document summarises the conclusions of a European Respiratory Society Task Force on the diagnosis and management of obstructive sleep disordered breathing (SDB) in childhood and refers to children aged 2-18 years. Prospective cohort studies describing the natural history of SDB or randomised, double-blind, placebo-controlled trials regarding its management are scarce. Selected evidence (362 articles) can be consolidated into seven management steps. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are present (step 1). Central nervous or cardiovascular system morbidity, growth failure or enuresis and predictors of SDB persistence in the long-term are recognised (steps 2 and 3), and SDB severity is determined objectively preferably using polysomnography (step 4). Children with an apnoea-hypopnoea index (AHI) >5 episodes·h(-1), those with an AHI of 1-5 episodes·h(-1) and the presence of morbidity or factors predicting SDB persistence, and children with complex conditions (e.g. Down syndrome and Prader-Willi syndrome) all appear to benefit from treatment (step 5). Treatment interventions are usually implemented in a stepwise fashion addressing all abnormalities that predispose to SDB (step 6) with re-evaluation after each intervention to detect residual disease and to determine the need for additional treatment (step 7).

Adenotonsillectomy and orthodontic therapy in pediatric obstructive sleep apnea.

PURPOSE: Rapid maxillary expansion (RME) is an additional treatment in pediatric obstructive sleep apnea (OSA). The aim of this study was to present data about the outcome of adenotonsillectomy (AT) and of RME in a clinical sample of pediatric OSA. METHODS: We consecutively enrolled children with OSA to undergo RME or AT. The age and the severity of OSA are the main factors involved in the choice of treatment. A polysomnography was performed at the baseline (i.e., before treatment, T0) and 1 year after treatment (T1). RESULTS: A total of 52 subjects fulfilled the inclusion criteria. Twenty-five children underwent AT (group 1) and 22 children underwent RME (group 2). Five children underwent both treatments (group 3). Children in group 2 were older, had a longer disease duration, a higher body mass index (BMI), a lower apnea-hypopnea index (AHI), and a lower arousal index at T0 than children in group 1. After 1 year, BMI percentile and overnight mean saturation increased in group 1 while AHI and arousal index decreased. In group 2, mean overnight saturation increased while AHI decreased. Children in group 3 displayed a significant decrease in AHI from T0 to T1. CONCLUSIONS: Our data demonstrate that both treatments help to improve OSA, and a multidisciplinary approach to treatment is suggested.

Individualized approaches to pediatric chronic insomnia: Advancing precision medicine in sleep disorders.

The manifestations of chronic insomnia undergo age-related changes. In younger infants and children, behavioral insomnia emerges as the most prevalent form and typically responds to behavioral interventions. However, distinct clusters of clinical presentations suggest the presence of various phenotypes, potentially implicating the primary involvement of specific neurotransmitters. These conceptualizations, coupled with genetic studies on pleiotropy and polygenicity, may aid in identifying individuals at risk of persistent insomnia into adulthood and shed light on novel treatment options. In school-age children, the predominant presentation is sleep-onset insomnia, often linked with nighttime fears, anxiety symptoms, poor sleep hygiene, limit-setting issues, and inadequate sleep duration. The manifestations of insomnia in adolescence correlate with the profound changes occurring in sleep architecture, circadian rhythms, and homeostatic processes. The primary symptoms during adolescence include delayed sleep onset, sleep misperception, persistent negative thoughts about sleep, and physiological hyperarousal-paralleling features observed in adult insomnia. An approach centered on distinct presentations may provide a framework for precision-based treatment options. Enhanced comprehension of insomnia's manifestations across diverse developmental stages can facilitate accurate assessment. Efforts to subtype insomnia in childhood align with this objective, potentially guiding the selection of appropriate treatments tailored to individual neurobiological, clinical, and familial features.

SPHYNCS: Feasibility of long-term monitoring with Fitbit smartwatches in central disorders of hypersomnolence and extraction of digital biomarkers in narcolepsy.

The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a multicenter research initiative to identify new biomarkers in central disorders of hypersomnolence (CDH). Whereas narcolepsy type 1 (NT1) is well characterized, other CDH disorders lack precise biomarkers. In SPHYNCS, we utilized Fitbit smartwatches to monitor physical activity, heart rate, and sleep parameters over one year. We examined the feasibility of long-term ambulatory monitoring using the wearable device. We then explored digital biomarkers differentiating patients with NT1 from healthy controls (HC). A total of 115 participants received a Fitbit smartwatch. Using a compliance metric to evaluate the usability of the wearable device, we found an overall compliance rate of 80% over one year. We calculated daily physical activity, heart rate, and sleep parameters from two weeks of greatest compliance to compare NT1 (n=20) and HC (n=9) subjects. Compared to controls, NT1 patients demonstrated findings consistent with increased sleep fragmentation, including significantly greater wake-after-sleep onset (p=0.007) and awakening index (p=0.025), as well as standard deviation of time in bed (p=0.044). Moreover, NT1 patients exhibited a significantly shorter REM latency (p=0.019), and sleep latency (p=0.001), as well as a lower peak heart rate (p=0.008), heart rate standard deviation (p=0.039) and high-intensity activity (p=0.009) compared to HC. This ongoing study demonstrates the feasibility of long-term monitoring with wearable technology in patients with CDH and potentially identifies a digital biomarker profile for NT1. While further validation is needed in larger datasets, these data suggest that long-term wearable technology may play a future role in diagnosing and managing narcolepsy.

Sleep clinical record: an aid to rapid and accurate diagnosis of paediatric sleep disordered breathing.

Overnight polysomnography (PSG) is an expensive procedure which can only be used in a minority of cases, although it remains the gold standard for the diagnosis of sleep disordered breathing (SDB). The objective of this study was to develop a simple, PSG-validated tool to screen SDB, thus reducing the use of PSG. For every participant we performed PSG and a sleep clinical record was completed. The sleep clinical record consists of three items: physical examination, subjective symptoms and clinical history. The clinical history analyses behavioural and cognitive problems. All three items were used to create a sleep clinical score (SCS). We studied 279 children, mean ± SD age 6.1 ± 3.1 years, 63.8% male; 27.2% with primary snoring and 72.8% with obstructive sleep apnoea (OSA) syndrome. The SCS was higher in the OSA syndrome group compared to the primary snoring group (8.1 ± 9.6 versus 0.4 ± 0.3, p<0.005), correlated with apnoea/hypopnoea index (p=0.001) and had a sensitivity of 96.05%. Positive and negative likelihood ratios were 2.91 and 0.06, respectively. SCS may effectively be used to screen patients as candidates for PSG study for suspected OSA syndrome, and to enable those with a mild form of SDB to receive early treatment.

The cooccurrence of interictal discharges and seizures in pediatric sleep-disordered breathing.

Studies in the literature data have shown that the prevalence of obstructive sleep apnea (OSA) in children with epilepsy is high and that treatment for OSA leads to a reduction in the number of seizures; by contrast, few studies have demonstrated an increased prevalence of interictal epileptiform discharges (IEDs) or epilepsy in children with sleep-disordered breathing (SDB). The aim of the present study was to confirm the high prevalence of IEDs or epilepsy in a large sample of children with SDB and to collect follow-up data. Children were recruited prospectively and underwent their first video-polysomnography (video-PSG) for SDB in a teaching hospital sleep center. Of the 298 children who fulfilled the diagnostic criteria for sleep-disordered breathing, 48 (16.1%) children were found to have IEDs, three of these 48 children were also found to have nocturnal seizures (two females diagnosed with rolandic epilepsy and a male diagnosed with frontal lobe epilepsy). Only 11 subjects underwent a second video-PSG after 6months; at the second video-PSG, the IEDs had disappeared in six subjects, who also displayed a reduced AHI and an increased mean overnight saturation. Thirty-eight of the 250 children without IEDs underwent a second video-PSG after 6months. Of these 250 children, four, who did not display any improvement in the respiratory parameters and were found to experience numerous stereotyped movements during sleep, were diagnosed with nocturnal frontal lobe epilepsy. Our study confirms the high prevalence of IEDs in children with SDB. Follow-up data indicate that they may recede over time, accompanied by an improvement of sleep respiratory parameters.

Whole-brain voxel-based morphometry study of children and adolescents with Down syndrome.

In order to investigate alterations in brain morphology and a possible temporal pattern of neuroanatomical abnormalities in the gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) of young patients with Down syndrome (DS), high-resolution magnetic resonance imaging (MRI) voxel-based morphometry (VBM) was performed on 21 children and adolescents with this chromosomal aberration and 27 age-matched participants as controls. In comparison with control subjects, children and adolescents with DS showed not only an overall smaller whole-brain volume, but also volume reductions of the GM in the cerebellum, frontal lobes, frontal region of the limbic lobe, parahippocampal gyri and hippocampi and of the WM in the cerebellum, frontal and parietal lobes, sub-lobar regions and brainstem. By contrast, volume preservation was observed in the GM of the parietal lobes, temporal lobe and sub-lobar regions and in the WM of the temporal lobe and temporal regions of the limbic lobe. A lower volume of CSF was also detected in the frontal lobes. This study is the first to use the high-resolution MRI VBM method to describe a whole-brain pattern of abnormalities in young DS patients falling within such a narrow age range and it provides new information on the neuroanatomically specific regional changes that occur during development in these patients.

Migraine and periodic limb movement disorders in sleep in children: a preliminary case-control study.

BACKGROUND: The relationships between sleep and headaches are complex and manifold. About the variety of phenomena that can disrupt the sleep macrostructure and can impact its restorative function, the periodic limb movements disorder (PLMd) can be considered as the most powerful.No studies are known about the role of PLMd in the pathophysiology of migraine in children.Aim of study is to assess the prevalence of PLMd and migraine and their relationship with disability and pain intensity in a pediatric sample, referred for migraine without aura by pediatricians. METHODS: After a preliminary sleep habits screening with the Sleep Disturbances Scale for Children, 34 migraine subjects affected by migraine without aura (20 M, 14 F) (mean age 9.08; SD ± 2.28) and 51 volunteers healthy children (28 M, 23 F) (mean age 9.37; SD ± 1.81) accepted to underwent overnight PSG recordings in the Sleep Laboratory of the Clinic of Child and Adolescent Neuropsychiatry, in order to define the macrostructural sleep characteristics and the prevalence of PLMd. Subsequently, the migraineurs sample was studied in order to define the relationship between disability, pain intensity, therapeutical responsiveness and the presence of PLMd. RESULTS: In the migraineurs children group, the individuals with PLM pathological index (PLMI ≥ 5) represent the 26.47% of sample and present higher frequency (p < 0.001), intensity (p < 0.001), duration (p = 0.006) and life impairment as scored in the PedMIDAS (p < 0.001) of headache and lower efficacy of prophylactic (p = 0.001) and acute (p = 0.006) pharmacological treatment than MoA children without PLM pathological index. CONCLUSIONS: This preliminary study indicates the potential value of the determination of the PLMd signs, and the importance of the PSG evaluation in children affected by migraine, particularly when the clinical and pharmacological management tend to fail in the attacks control.

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

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

Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis.

STUDY OBJECTIVES: Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome, but their impact on sleep is still debated, as well the indication for treatment. We systematically reviewed the available literature to describe which drug categories are effective in suppressing PLMS, assessing their efficacy through a meta-analysis, when this was possible. METHODS: The review protocol was preregistered on PROSPERO (CRD42021175848), and the systematic search was conducted on and EMBASE (last searched on March 2020). We included original human studies, which assessed PLMS modification on drug treatment with a full-night polysomnography, through surface electrodes on each tibialis anterior muscle. When at least 4 studies were available on the same drug or drug category, we performed a random-effect model meta-analysis. RESULTS: Dopamine agonists like pramipexole and ropinirole resulted the most effective, followed by l-dopa and other dopamine agonists. Alpha2delta ligands are moderately effective as well opioids, despite available data on these drugs are much more limited than those on dopaminergic agents. Valproate and carbamazepine did not show a significant effect on PLMS. Clonazepam showed contradictory results. Perampanel and dypiridamole showed promising but still insufficient data. The same applies to iron supplementation. CONCLUSIONS: Dopaminergic agents are the most powerful suppressors of PLMS. However, most therapeutic trials in restless legs syndrome do not report objective polysomnographic findings, there is a lack of uniformity in presenting results on PLMS. Longitudinal polysomnographic interventional studies, using well-defined and unanimous scoring criteria and endpoints on PLMS are needed. CITATION: Riccardi S, Ferri R, Garbazza C, Miano S, Manconi M. Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis. J Clin Sleep Med. 2023;19(4):811-822.