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Some clinical studies on attention deficit hyperactivity disorder (ADHD) have been found to overlap those of studies on personality, particularly those on the Novelty Seeking trait (NS) as measured by the Junior Temperament and Character Inventory (JTCI). The aim of this study was to evaluate the potential role of NS in clinical research on ADHD. We enroled 146 ADHD children (125 boys; mean age=9.61, S.D.=2.50) and 223 age- and gender-matched control children (178 boys; mean age=9.41, S.D.=2.30). All the parents filled in the JTCI for the evaluation of personality according to Cloninger׳s model. An exploratory factor analysis differentiated the NS items that concern “Impulsivity” (NS1) from those that concern other features (NS2). Multivariate Analysis of Variance (MANOVAs) revealed significant differences between ADHD children and non-ADHD children in temperamental dimensions: the scores of ADHD children were higher than those of non-ADHD children in Total NS, NS1-Impulsivity and NS2. Our results show that the NS dimension of the JTCI in ADHD children is higher than in non-ADHD children, even when a correction is made for impulsivity items. This finding suggests that the NS trait plays a central role in ADHD diagnosis even when items referred to impulsivity are removed from the NS scale.

Objectives The objective of this study was to evaluate the impact of obesity on cognitive impairment, in children with obstructive sleep apnoea (OSA), children with OSA and obesity, and in normal controls. Methods Thirty-six children with OSA (group 1), 38 children with OSA and obesity (group 2) and 58 normal controls (group 3) were studied. The Total intelligence quotient (T-IQ), Verbal IQ (V-IQ) and the Performance IQ (P-IQ) scores were obtained using the Wechsler Intelligence Scale for Children – Third Edition Revised. All participants' parents filled out the questionnaire containing the attention deficit and hyperactive disorder rating scale to investigate symptoms of hyperactivity and attention deficit. Obese and non-obese children with sleep-disordered breathing (SDB) underwent polysomnography. Results T-QI and P-QI scores were significantly lower in group 2 with higher performance impairment at the subtest compared to other groups. In obese children, V-IQ was significantly correlated with age of onset ( r = 0.335, p = 0.05) and duration of SDB ( r = −0.362, p = 0.02), while P-IQ and T-IQ were correlated with body mass index (BMI) percentile ( r = −0.341, p = 0.03) and respiratory disturbance index (RDI) ( r = −0.321, p = 0.05), respectively. RDI and BMI negatively influenced T-IQ in obese children with OSA. No correlation was found between sleep parameters and IQ scores or subtest scores in all groups. Conclusions Obese children with OSA showed higher cognitive impairment. Obesity has an additive and synergic action with that exerted by OSA, speeding up the onset of complications.

Study Objectives: To analyze the intervals between A phases of the cyclic alternating pattern (CAP) and to describe their time structure. This might represent an additional aspect to be studied in sleep pathologies that are accompanied by CAP changes. Methods: Sleep stages and CAP A phases were identified in polysomnographic night recordings of normal adults and children. Intervals between consecutive CAP A phases were measured, counted, and used to draw individual normalized distribution graphs. The intervals during light sleep (stages 1 and 2) were analyzed separately from those occurring during slow-wave sleep (SWS). Subsequently, we performed a Markovian analysis of intervals, in order to describe in detail their time structure. Setting: N/A. Participants: Twenty-four adults and 28 children. Measurements and Results: In adults, a preponderance of intervals shorter than 60 seconds during SWS was found; light sleep showed a higher number of intervals longer than 60 seconds. A less clear-cut difference between stages was found in children, who showed a shift of the peak in their SWS histogram toward intervals shorter than in adults. Interval sequences were not determined by a random process in both groups. The Markovian analysis showed statistically significant lower values of entropy and higher values of time dependency, mostly in adults during SWS. Conclusions: The different CAP components of sleep occur in a non-random ordered fashion, and their time structure is characterized by first-order relationships. Significance: We postulate that CAP components are the expression of a timely ordered process that exhibits specific sleep stage-related features and undergoes age-related modifications.

Sleep disturbances are frequent in Angelman syndrome (AS); however, beside the few studies which have investigated sleep disorders in AS by means of questionnaires, to our knowledge, no systematic polysomnographic recordings have been carried out in AS patients. The present study represents the first attempt to study sleep patterns of AS by polysomnography, to evaluate the influences of sleep on the paroxysmal electroencephalogram (EEG) patterns of AS and to assess the eventual age-related changes of sleep architecture and of sleep EEG abnormalities in children and adolescents with AS.Fifteen children with AS (7 males and 8 females, mean age 7.2 years, range 3-16 years), attending the Sleep Center of the Department of Child Neurology and Psychiatry of the University of Rome 'La Sapienza' and the Sleep Research Centre of the Oasi Institute (IRCCS) of Troina were included and subdivided into two subgroups by age: subgroup 1, aged 3-5 years, and subgroup 2, aged 9-17 years. Two control groups of age-matched normal subjects were also included: one aged less than 8 years and another aged more than 8 years; additionally, two other groups of age-matched children with epilepsy and mental retardation of different origin, one aged less and one aged more than 9 years were taken into consideration. The statistical comparison between the sleep parameters obtained from the patients and those from the other groups was carried out by means of the non-parametric Kruskal-Wallis ANOVA and the Mann-Whitney U test.The most frequent EEG abnormality found in AS patients appeared to be the 2-3 c/s poorly defined spike/waves complexes. This pattern was influenced by sleep stages; the duration of the runs showed an increasing length with sleep deepening from sleep stage 1 to slow-wave sleep (SWS). Moreover, the 2-3 c/s bursts activity present in sleep stage 2 showed a slowing to 1-2 c/s during SWS. Regarding sleep architecture, in subjects with AS aged8 year there was a significant reduction in sleep efficiency as compared to normal controls, while the percentage and duration of REM sleep was significantly lower and the percentage of SWS was significantly higher. REM sleep time was reduced in AS subjects aged8 years than in normal controls. The comparison between AS groups and mental retardation with epilepsy groups did not show significant differences.Similarly to other types of genetically determined mental retardation syndromes, also subjects with AS seems to show important abnormalities of their sleep polysomnographic patterns.This is the first study which reports, in detail, these abnormalities and opens a new path for further insight into the knowledge of additional sleep-related disturbances which are reported in sleep questionnaires by the caregivers of AS subjects.

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. 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). 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. Our data demonstrate that both treatments help to improve OSA, and a multidisciplinary approach to treatment is suggested.

In our previous study we found a high prevalence of disordered sleep breathing in migraine children vs. controls. Since no quantitative studies about sleep respiratory disorders have been carried out in migraine children, we performed a polysomnographic (PSG) study in 10 migraine patients (7 boys, 3 girls; mean age 8.11 years, range, 5.8–14.5) attending the Headache Center of our department, to evaluate the presence of sleep apnea. Mothers completed a headache diary and a sleep diary for at least 1 month and filled out a sleep questionnaire. PSG data showed a normal sleep architecture in 3 cases, an insomnia pattern in 2, a reduction of slow wave sleep in 3 and a reduction of REM sleep in 2. Respiratory analysis revealed that 2 of 10 patients had obstructive sleep apnea. These 2 patients presented habitual snoring and associated sleep disturbances such as restless sleep and hypnic jerks. Sleep apnea may be a subtle and often undiagnosed symptom in several migraine patients. The report of habitual snoring associated with other sleep disturbances such as restless sleep and other parasomnias may be a sign of sleep apnea in migraine children.

We designed a 3-month open label trial of melatonin prophylaxis in children with primary headache. After a one month baseline period without receiving preventive drugs, all children received a 3-month course of melatonin, 3 mg, administered orally, at bedtime. A total of 22 children were enrolled (10 boys, mean age 12.2+/-2.6 years, age range 6-16 years), 13 had recurrent migraine without aura, 1 with aura and 8 had chronic tension-type headache. When the trial ended, 14 of the 21 subjects reported that the headache attacks had decreased by more than 50% in respect to baseline and 4 of them reported having no headache attacks. After receiving melatonin for one month one subject dropped out because of excessive daytime sleepiness. Our promising results warrant randomized placebo-controlled trials in children to assess the real effectiveness of melatonin in preventing primary headache.

Pediatric insomnia is an extrinsic sleep disorder subdivided into two categories: behavioral insomnia and insomnia related to medical, neurological, and psychiatric diseases. This review will cover several types of insomnia, comorbidities and specific pediatric therapies according to clinical characteristics and age. Behavioral insomnia should be differentiated from pediatric insomnia due to medical conditions, mostly occurring during the first year of life. Multiple night awakenings and diurnal hypersomnolence are strong indicators of insomnia due to medical conditions. Insomnia during adolescence and pediatric insomnia associated with psychiatric comorbidity, cognitive disabilities and epilepsy, will be discussed in terms of diagnosis, clinical features and implications for treatment.Insomnio pediatrico: clinica, diagnostico y tratamiento.El insomnio pediatrico es un trastorno de sueño extrinseco que puede subdividirse en dos categorias: insomnio conductual e insomnio relacionado con trastornos medicos, neurologicos y psiquiatricos. En esta revision presentamos varios tipos de insomnios, comorbilidad y terapias especificas de acuerdo con la edad y con las caracteristicas clinicas. El insomnio conductual se debe diferenciar del insomnio pediatrico por causas medicas, ya que este ultimo aparece, normalmente, en el primer año de vida. Los despertares nocturnos frecuentes y la somnolencia diurna excesiva indican un insomnio debido a causas medicas. El insomnio del adolescente y el insomnio pediatrico asociado a trastornos psiquiatricos, alteraciones cognitivas y epilepsia se discutiran en terminos de diagnostico, hallazgos clinicos e implicaciones terapeuticas.

Because signs of nocturnal seizures can overlap with sleep respiratory events, clinicians can have difficulty distinguishing abnormal events related to sleep disorders from epileptic seizures. We describe the case of a 3-year-old child presenting with ictal electroencephalographic (EEG) activity associated with a particular form of atypical obstructive sleep apnea, characterized by increased respiratory rate, paradoxical breathing, desaturations, and tonic-dystonic posture associated with movement artifacts. Following cardiorespiratory polysomnography, the patient was initially misdiagnosed as having severe obstructive sleep apnea syndrome.

Objective: Five sleep ADHD phenotypes have been hypothesized: (a) the hypo-arousal state of the “primary” form of ADHD, (b) the sleep phase advanced disorder, (c) sleep disordered breathing (SDB), (d) restless legs syndrome and/or periodic limb movements disorder (PLMD), and (e) epilepsy. Method: Five case reports are presented; each child but one underwent video-polysomnography. Results: The first case report is an example of ADHD and SDB, with improvement of hypersomnolence after resolution of sleep apnea. The second case shows the impact of delayed sleep onset latency in the pathogenesis of ADHD, and the efficacy of melatonin. The third case report describes the association with PLMD, with amelioration after iron supplementation. The other two cases are examples of ADHD and epilepsy, with clinical improvement after antiepileptic treatment was started. Conclusion: A diagnostic and therapeutic algorithm should be designed to find the best first-line treatment for ADHD and sleep problems/epilepsy.

Objective To evaluate the presence of Major Depressive Disorder (MDD) and Dysthymic Disorder (DD) in a sample of Italian children with Attention Deficit Hyperactivity Disorder (ADHD) and to explore specific features of comorbid depressive disorders in ADHD. Methods Three hundred and sixty-six consecutive, drug-naive Caucasian Italian outpatients with ADHD were recruited and comorbid disorders were evaluated using DSM-IV-TR criteria. To evaluate ADHD severity, parents of all children filled out the ADHD Rating Scale. Thirty-seven children with comorbid MDD or DD were compared with 118 children with comorbid conduct disorder and 122 without comorbidity for age, sex, IQ level, family psychiatric history, and ADHD subtypes and severity. Results 42 of the ADHD children displayed comorbid depressive disorders: 16 exhibited MDD, 21 DD, and 5 both MDD and DD. The frequency of hyperactive-impulsive subtypes was significantly lower in ADHD children with depressive disorders, than in those without any comorbidity. ADHD children with depressive disorders showed a higher number of familial psychiatric disorders and higher score in the Inattentive scale of the ADHD Rating Scale, than children without any comorbidity. No differences were found for age, sex and IQ level between the three groups. Conclusion Consistent with previous studies in other countries, depressive disorders affect a significant proportion of ADHD children in Italy. Patient assessment and subsequent treatment should take into consideration the possible presence of this comorbidity, which could specifically increase the severity of ADHD attention problems.

INTRODUCTION. We present a series of children who underwent a video-polysomnographic recording at our Sleep and Epilepsy Unit, who received a diagnosis of nocturnal frontal lobe epilepsy (NFLE). AIMS. To describe electroclinical and video polygraphic features of paediatric NFLE that differentiate this condition from other sleep disorders that overlap and mimic the sleep motor and autonomic events of NFLE. PATIENTS AND METHODS. The inclusion criterion was that the patients have their first video-EEG-PSG recording in our laboratory. RESULTS. Twenty-four out of 190 children were diagnosed with NFLE (group 1); while 166 had other sleep disorders (group 2). Among children diagnosed with NFLE, seven were referred for sleep-disordered breathing, seven for parasomnias, two for insomnia, two for hypersomnia, and one for periodic limb movements, while five were referred for epilepsy. In group 1, perinatal history was normal in most cases (21 out of 24) and a familiar history of epilepsy was found in four cases. Sleep-disordered breathing was diagnosed as a comorbid condition in four children. Standard EEG was normal in 21 cases. Interictal EEG showed epileptic discharges in four cases, while ictal EEG was expressed by a rhythmic theta activity preceded by an arousal and/or a short background desynchronization, movement artifacts, and autonomic changes. All seizures, repeated highly stereotyped motor events, were followed by stage shifts and/or a postural change and, by short awakenings. CONCLUSIONS. We found a high percentage of children with NFLE, often misdiagnosed or associated with other sleep disorders, which may be a trigger for nocturnal seizures.

The objective was to review and compare outcomes after tongue-lip adhesion (TLA) and mandibular distraction osteogenesis (MDO) in infants with severe breathing difficulties related to Pierre Robin sequence (PRS). A single-centre retrospective (2002-2012) study was carried out; 18 infants with severe breathing difficulties related to PRS resistant to conservative treatment, who underwent TLA or MDO to correct airway obstruction, were enrolled. The primary outcome measures were successful weaning from respiratory support and resumption of full oral feeding. Nine underwent TLA and nine MDO. Eight of the nine infants who underwent MDO and all those treated with TLA were successfully weaned from respiratory support. After discharge, residual respiratory distress was diagnosed more commonly after TLA than after MDO (6/9 vs 1/9, P=0.050). Infants resumed oral feeding sooner after MDO than after TLA (mean days after surgery to full oral feeds 44±24 vs 217±134, P

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. © 2013 Esposito et al.; licensee Springer.

About 25-50% of children and adolescents with attention-deficit hyperactivity disorder (ADHD) experience sleep problems. An appropriate assessment and treatment of such problems might improve the quality of life in such patients and reduce both the severity of ADHD and the impairment it causes. According to data in the literature and to the overall complexity of the interaction between ADHD and sleep, five sleep phenotypes may be identified in ADHD: (i) a sleep phenotype characterized mainly by a hypo-arousal state, resembling narcolepsy, which may be considered a "primary" form of ADHD (i.e. without the interference of other sleep disorders); (ii) a phenotype associated with delayed sleep onset latency and with a higher risk of bipolar disorder; (iii) a phenotype associated with sleep disordered breathing (SDB); (iv) another phenotype related to restless legs syndrome (RLS) and/or periodic limb movements; (v) lastly, a phenotype related to epilepsy/or EEG interictal discharges. Each sleep phenotype is characterized by peculiar sleep alterations expressed by either an increased or decreased level of arousal during sleep that have important treatment implications. Treatment with stimulants is recommended above all in the primary form of ADHD, whereas treatment of the main sleep disorders or of co-morbidities (i.e. bipolar disorders and epilepsy) is preferred in the other sleep phenotypes. All the sleep phenotypes, except the primary form of ADHD and those related to focal benign epilepsy or focal EEG discharges, are associated with an increased level of arousal during sleep. Recent studies have demonstrated that both an increase and a decrease in arousal are ascribable to executive dysfunctions controlled by prefrontal cortical regions (the main cortical areas implicated in the pathogenesis of ADHD), and that the arousal system, which may be hyperactivated or hypoactivated depending on the form of ADHD/sleep phenotype.

Orthodontic and craniofacial abnormalities have often been reported in pediatric sleep-disordered breathing (SDB). While the reversibility of these craniofacial abnormalities by means of adenotonsillectomy has yet to be established, orthodontic treatment based on oral appliances is considered to be a potential additional treatment for pediatric SDB. Oral appliances may help improve upper airway patency during sleep by enlarging the upper airway and/or by decreasing upper airway collapsibility, thereby enhancing upper airway muscle tone. Orthodontic therapy should be encouraged in pediatric OSAS, and an early approach may permanently modify nasal breathing and respiration, thereby preventing obstruction of the upper airway.

Orthodontic and craniofacial abnormalities associated with pediatric sleep-disordered breathing (SDB) are, despite their impact on public health, widely ignored: a narrow upper airway with maxillary constriction and/or some degree of mandibular retrusion is a common phenotype of pediatric obstructive sleep apnea syndrome (OSAS). In such cases, children are typically described as having a narrow, long face. Several anatomical and functional mechanisms may lead to OSAS in children and in adults, one being a smaller upper airway, which predisposes subjects to airway collapse during sleep in all age groups.

Objective Previous studies have been inconclusive whether dominant resting state alpha rhythms differ in amplitude in dyslexic subjects when compared to control subjects, being these rhythms considered as a reflection of effective cortical neural synchronization and cognition. Here we used a validated EEG source estimation to test the hypothesis that resting state alpha rhythms are abnormal in dyslexic subjects and are related to reading deficits. Methods Eyes-closed resting state electroencephalographic (EEG) data were recorded in 26 dyslexics (12 males, mean age of 11 years ± 0.5 standard error of mean, SEM) and 11 age-matched normal control subjects (8 males, mean age of 11 years ± 0.7 SEM). EEG rhythms of interest, based on individual alpha frequency peak, were the following: about 2–4 Hz (delta), 4–6 Hz (theta), 6–8 Hz (alpha 1), 8–10 Hz (alpha 2), and 10–12 Hz (alpha 3). For the higher frequencies, we selected beta 1 (13–20 Hz), beta 2 (20–30 Hz), and gamma (30–40 Hz). Cortical EEG sources were estimated by low resolution electromagnetic tomography (LORETA). LORETA solutions were normalized across all voxels and frequencies. Results Compared to the control children, the dyslexics showed lower amplitude of parietal, occipital, and temporal alpha 2 and alpha 3 sources. In the dyslexics, some of these sources were correlated to reading time of pseudo-words (parietal alpha 2, r = −0.56, p = 0.02; parietal alpha 3, r = −0.58, p = 0.02; temporal alpha 3, r = −0.57, p = 0.02); the higher the alpha power, the shorter the reading time. Conclusions Dyslexic children are characterized by limited abnormalities of resting state EEG rhythms as to topography (posterior regions) and frequency (alpha), which were related to phonological encoding (pseudo-words reading). Significance Dyslexia may be associated to some functional impairment of cortical neuronal synchronization mechanisms involved in the resting state condition.

In view of the positive outcome of orthodontic treatment using rapid maxillary expansion (RME) on sleep-disordered breathing, we generated data on RME in children with obstructive sleep apnea (OSA) by evaluating objective and subjective data over a 36-month follow-up period, to determine whether RME is effective in the long-term treatment of OSA. We selected all patients with dental malocclusions and OSA syndrome (OSAS) confirmed by polysomnography.Ten of the 14 children who completed the 12-month therapeutic trial using RME were enrolled in our follow-up study. The study was performed 24 months after the end of the RME orthodontic treatment. We enrolled all children presented with deep, retrusive or crossbite at the orthodontic evaluation. All subjects underwent an overnight polysomnography at the baseline, after 1 year of treatment and 24 months after the end of the orthodontic treatment. The children's mean age was 6.6 ± 2.1 years at entry and 9.7 ± 1.6 years at the end of follow-up.After treatment, the apnea hypopnoea index (AHI) decreased and the clinical symptoms had resolved by the end of the treatment period. Twenty-four months after the end of the treatment, no significant changes in the AHI or in other variables were observed.RME may be a useful approach in children with malocclusion and OSAS, as the effects of such treatment were found to persist 24 months after the end of treatment.

We evaluated the cyclic alternating pattern (CAP) during the first year of life in order to obtain information on the maturation of arousal mechanisms during NREM sleep and to provide normative data for CAP parameters in this age range (5–16 months). Eleven healthy children (mean age 7.9 ± 3.3 months, seven boys) were studied while they slept in the morning. They underwent a 3-h video-EEG-polysomnographic recording at the Pediatric Sleep Unit of Sant’Andrea Hospital in Rome, Italy. Sleep was scored visually for sleep architecture and CAP analysis using standard criteria. Our results were complemented by CAP data from a previous sample of healthy infants (2–4 months), studied when they slept during the morning, in order to correlate CAP parameters with age. The total sample comprised 24 children. The sleep period was approximately 2 h, with a first REM latency of about 30 min, and a clear distinction between stages N1, N2, and N3. The arousal index was 12 ± 2.1 events/hour of sleep. The total CAP rate was 23.7 ± 7.6%, and it increased progressively with the deepness of sleep; the highest values were observed during stage N3 and the lowest values during stage N1. A1 phases were the most numerous (78.2%), followed by A2 (14%) and A3 (7.7%) phases. The A1 index was higher than the A2 and A3 indices, whereas the mean duration of B was higher than that of A. The correlation showed that the CAP rate, A1, A2, A3 indices, A2, A3 percentages, and the average duration of B increased with age, whereas the A1 percentage decreased. We provide the first data on CAP analysis in children aged 5–16 months, studied when they slept during the morning. Our results confirm the trend toward an increase in CAP rate during the first year of life. In addition, we observed a progressive increase in CAP rate with deepness of sleep, and with age, reflecting maturation of slow-wave activity. The decreased percentage of A1 subtypes may reflect the maturation of arousability.

Insomnia is the predominant sleep concern in children with autistic spectrum disorder (ASD), and its nature is most likely multifactorial, with neurochemical (abnormalities in serotonergic transmission or melatonin levels), psychiatric (anxiety), and behavioral (poor sleep habits) etiological factors involved. Children with ASD experience sleep problems similar to those of typically developing children, although the prevalence is markedly higher, occurring in 44-83% of school-aged children with ASD. Caregivers usually report that insomnia is the most frequent sleep disorder, described as disorders of initiating and maintaining sleep, restless sleep, bedtime resistance, co-sleeping, alterations of sleep hygiene, and early awakenings in the morning. Many actigraphic studies have added information on sleep disorders, confirming the questionnaire findings in the majority of cases. There are relatively few polysomnographic data for ASD, compared with questionnaire studies, and most of these studies reported a reduction in total sleep time and more undifferentiated sleep in the youngest patients. These findings were associated with several sleep microstructure alterations during rapid eye movement (REM) sleep, and with non-REM (NREM) sleep microstructure changes that appeared to be related to cognitive impairment rather than to the autistic core. Moreover, few data about other less frequent sleep disorders, such as periodic limb movements disorder and obstructive sleep apnea syndrome, bruxism, and the influence of epilepsy and EEG abnormalities, are available. Both pharmacologic and behavioral interventions have been suggested for the treatment of sleep problems in autistic children. The most common types of behavioral interventions are complete extinction (removing reinforcement to reduce a behavior) and various forms of graduated extinction. Melatonin has shown promising results in the treatment of insomnia in children with ASD. Although controlled studies are limited, there are more data demonstrating the safety and effectiveness of melatonin in ASD than for other sedative/hypnotic drugs. Finally, a dual treatment for insomnia in ASDs with melatonin and behavioral techniques has been suggested. A recent study using a combination of genetic and functional experimental techniques reported evidence that low melatonin concentration caused by a primary deficit in acetylserotonin methyltransferase activity is a risk factor for ASD. Sleep problems usually start at the same age as developmental regression, suggesting a higher vulnerability at this period of life. Further studies, beginning at younger ages, are necessary to better investigate these aspects and the role of melatonin in insomnia in children with ASD.

Purpose: Sleep breathing disorders (SBD) can trigger paroxysmal events. We recently found a higher percentage of paroxysmal activity (PA) in a sample of Italian children with obstructive sleep apnea syndrome (OSAS) and no history of epilepsy. The signs of nocturnal seizures can overlap with sleep respiratory events. The aim of this study was to confirm the high frequency of PA or interictal epileptiform discharges (IEDs) during sleep in a cohort of Spanish children who underwent polysomonography (PSG) for suspected SBD and to ascertain the eventual presence of seizures by means of a video-PSG with an extended electroencephalogram (EEG). Methods: PSG was performed in a population of children with no previous history of epileptic seizures recruited prospectively for suspected OSAS from January to December 2007. Recordings included at least 13 EEG channels. Results: In total, 25 children (mean age, 6.6 3.8 years, 14 males) were diagnosed with SBD, and 4/25 (16%) children met the criteria for OSAS and epilepsy, with IEDs and/or seizures during sleep. We diagnosed benign epilepsy with centro-temporal spikes in 2 cases, partial symptomatic epilepsy in one, and nocturnal frontal lobe epilepsy in another, while we found PA in 2 patients. The body mass index and the apnea–hypopnea index were significantly higher in children without IEDs/PA. Conclusions: Our study demonstrated a close relationship between pediatric SBD, PA during sleep, and epilepsy that may aggravate the prognosis of SBD. Due to the possibility of an overlap of symptoms, a video-PSG with extended EEG montage is necessary.

The present study aimed at: (1) exploring rate and clinical features of superimposed bipolar disorder (BD) in Italian children with attention deficit hyperactivity disorder (ADHD), compared with a community sample, matched for age and gender; (2) exploring predictors of BD in ADHD children, by comparing ADHD children with or without superimposed BD. We studied 173 consecutive drug-naïve outpatients with ADHD (156 males and 17 females, mean age of 9.2 ± 2.3years, age range 6-17.5 years), diagnosed with a clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL)); the control group consisted of a community-based sample of 100 healthy children. The rate of children with a diagnosis of BD was higher in the ADHD group (29/173, 16.7%) compared with controls (1/100, 1%), (P0.001). Among the 29 children with ADHD+BD, 16 (55.2%) had a Bipolar Disorder-Not Otherwise Specified (BD-NOS), and 11 (37.9%) showed ultrarapid cycling. Compared with children with ADHD without BD, they showed a higher rate of combined sub-type (21/29, 72.4%), a higher score at ADHD-Rating Scale (total score and hyperactivity subscale), higher rates of major depression, oppositional defiant disorder and conduct disorder. In summary, children with ADHD present a higher risk for developing a superimposed BD. The identification of clinical features with an increased risk of BD can improve diagnosis, prognosis and treatments.

CHRONIC CARDIOVASCULAR AUTONOMIC ABNORMALITIES DURING BOTH SLEEP AND WAKEFULNESS HAVE BEEN DEMONSTRATED IN ADULTS WITH obstructive sleep apnea syndrome (OSAS), caused by sympathovagal balance alterations.1,–3 Persistent muscle sympathetic nerve activation and high levels of circulating norepinephrine increase the sympathetic drive in adults with OSAS.4, 5 At the same time, heart rate variability (HRV) during sleep is markedly reduced, which suggests impaired parasympathetic control.6 The pathogenesis of this persistent sympathetic activation has yet to be fully understood. Repetitive episodes of apnea cause hypoxia and sleep fragmentation, inducing tonic activation of chemoreflex activity, and an increase in sympathetic nerve activity, as, demonstrated by muscle sympathetic microneurography.7,–11 Studies in children with OSAS have reported increased blood pressure,12 changes in cardiac structure and function,13,14 increased fasting insulin and lipid levels,15,16 and endothelial dysfunction, as signs of cardiovascular damage.17,18 However, the few studies that have evaluated autonomic dysfunction reported an increase in diastolic blood pressure, both during wakefulness and sleep,19,20 as well as an increase in sympathetic activity, demonstrated by peripheral arterial tonometry,21,22 and catecholamine concentration measurements in plasma and urine.23 Yet other studies have documented an increase in HRV,24 and a drop in blood pressure during wakefulness, as assessed by the head-up tilt test, in children with OSAS.25 The head-up tilt test is part of the Ewing battery, which is a physiological test for the assessment of autonomic function.26 It studies cardiovascular autonomic reflexes by analyzing changes in heart rate and arterial pressure induced by a range of physiological stimuli. The aim of our study was to investigate the activity of the autonomic nervous system during wakefulness using the cardiovascular tests in a cohort of children with OSAS, in order to detect not only sympathetic, but also parasympathetic activity.

To compare the new American Academy of Sleep Medicine (AASM) criteria for scoring sleep with the previous Rechtschaffen and Kales (RK) criteria in a cohort of children with primary snoring, obstructive sleep apnea syndrome (OSAS) and normal controls.Polysomnography was performed in 26 consecutive children with primary snoring (13 males, mean age 6.2 years, SD 3.2), in 39 with OSAS (24 males, mean age 6.1 years, SD 3.0), and in 10 age-matched normal controls.Compared to the other groups, OSAS children showed a lower percentage of slow-wave sleep, using both RK and AASM criteria; they also showed a higher percentage of stage shifts, and N1, using the AASM criteria. Children with primary snoring showed a higher percentage of N1, compared to controls.These results indicate that the use of the new AASM criteria seem to disclose more differences in sleep parameters than the RK rules in children with OSAS.The AASM criteria seem to disclose a high degree of sleep fragmentation in children with OSAS, mostly related to the repeated occurrence of N1.

Objective To report our findings from a sample of narcoleptic children and adolescents evaluated in our unit from 1988 to 2005. Patients and methods The sample was composed of nine children (5 boys) with a mean age of 14.5 years at diagnosis. The protocol included the following: Epworth, Ullanlinna narcolepsy scale, and Stanford cataplexy questionnaires; physical, psychological and neurological examinations; neuroimaging; PSG + MSLT recordings; HLA and in two cases Hcrt-1 level in CSF. Results Narcolepsy was sporadic in all cases. The first symptom was EDS with a mean age at onset of 9.4 ± 2.5 years (range 6–13 years). All patients complained of cataplexy. Other symptoms were hypnagogic hallucinations (4 children) and sleep paralysis (3 children). All the children performed poorly at school, 4 had emotional disorders with depression, 4 displayed nocturnal eating and weight gain. Mean BMI was 25.0 kg/m2. One girl was diagnosed as having precocious puberty, polycystic ovary syndrome (PCOS), hyperandrogenism and insulin resistance. The MRI showed a partial empty sella. Hcrt-1 was undetectable in her CSF. The mean Ullanlinna score was 24.6; PSG showed disturbed nocturnal sleep and the MSLT showed a mean sleep latency of 2.1 min and 3 SOREMPs. Eight children were DR2-DQ1-positive, whereas one boy was DR2-negative but DQ1-positive. In two patients, Hcrt-1 was undetectable. All children, in addition to scheduled naps during the day, were treated with modafinil or methylphenidate combined with an antidepressant and in two cases with sodium oxybate. Conclusion NC was sporadic in all children and associated with precocious puberty and PCOS, hyperandrogenism and insulin resistance in one case. EDS, cataplexy, disturbed nocturnal sleep, nocturnal eating, poor school performance, and emotional disorders were the principal complaints. All patients had DQB1∗0602 and Hcrt-1 was evaluated in two cases (undetectable in both).

The aim of this study was to assess the presence of sleep breathing disorder and periodic leg movements during sleep (PLMS), and to evaluate NREM sleep instability in a group of children with mental retardation (MR) and epilepsy. Eleven subjects with MR and epilepsy (6 males, age range 9-17 years) were recruited for this study. A control group was formed by 11 age-matched normal children. Three children with MR and epilepsy showed an apnea-hypopnea index > 5, two of them had also a PLMS index > 5. Another subject had only a PLMS index > 5. Children with MR showed many sleep architecture differences compared to controls. They also showed higher cyclic alternating pattern (CAP) rate, increased A1 index, long and less numerous CAP sequences than controls. A detailed investigation and treatment of sleep disorders in children affected by MR and epilepsy may have a positive impact on seizure control.

SLEEP BREATHING DISORDERS (SBD) MAY TRIGGER PAROXYSMAL EVENTS DURING SLEEP SUCH AS PARASOMNIAS AND MAY EXACERBATE PREEXISTING seizures. Treatment of SBD can eliminate or reduce these events in adults and children.1–4 In a series of adolescents and adults the improvement of SBD after ventilatory therapy was associated to a reduction in interictal epileptic discharges (IEDs); even if the mechanism is still unclear, sleep stability seems to play an important role.1 SBD is commonly reported in children with epilepsy,5 and treatment of SBD may reduce seizure frequency and improve daytime sleepiness.4,6–12 These studies have focused on the role of sleep respiratory events as trigger factors for seizure or interictal discharges in subjects with epilepsy. There are no reports of IEDs or seizures activated by SBD in subjects without a history of epileptic seizures. Recently we reported IEDs in 5 children clinically diagnosed with OSA. Video-polysomnographic (video-PSG) recordings revealed partial motor nocturnal epileptic seizures associated with UARS.13 IEDs are usually activated during NREM sleep and suppressed during REM sleep.14–18 The activating properties of NREM sleep depend on the synchronizing functions of the thalamocortical oscillations.19,20 The strong association between NREM sleep and IEDs may be one mechanism explaining the impact of IEDs on learning and memory and on daytime behavior, although this area needs further investigation.21 Recently, PSG recordings revealed an epileptiform activity during sleep in 1.45% of otherwise healthy children. Most of epileptiform patterns were found in the centrotemporal regions and were associated with suboptimal cognitive and behavioral function.22 Many studies have provided data on the relationship between IEDs during sleep (particularly centrotemporal or rolandic spikes) and neuropsychological dysfunction in children with language disorders, autism, and ADHD.16,23–26 Furthermore, the neuropsychological assessment in children affected by benign epilepsy of childhood with centrotemporal or rolandic spikes (BECRS) and IEDs during sleep revealed disorders in visuospatial short-term memory, attention span, cognitive flexibility, verbal fluency, phonological awareness, visuoperceptual skills,27–30 and academic performance,30 with a significant improvement after the remission of IEDs.28 Many children with SBD show neurobehavioral complications. Intermittent hypoxemia and subtle changes in sleep architecture might be implicated in the pathogenesis of neurocognitive deficits in pediatric OSAS.31 The neurocognitive profile of children with OSAS shows some similarities with that found in children with IEDs with or without epileptic seizures. Since sleep respiratory events could trigger IEDs during sleep, we expected to find a high prevalence of EEG paroxysmal activity (PA) in children with OSAS, disclosed by means of PSG (with extended EEG leads). Thus, the aims of our study were: (1) to assess the presence of PA in a group of children undergoing a diagnostic assessment for OSAS, without a history of epilepsy, and (2) to compare children with PA with children who had OSAS and normal EEG patterns. We hypothesized there would be differences in clinical and polysomnographic features between these 2 groups.

Objective To evaluate NREM sleep microstructure in children with obstructive sleep apnea syndrome (OSAS) before and after one year of rapid maxillary expander (RME) treatment by means of the cyclic alternating pattern (CAP). Methods Nine children with OSAS aged 4–8 years (6 males, mean age 6.4 ± 1.97 years) and age-matched normal controls were included. All subjects underwent an overnight polysomnography in the sleep laboratory after one adaptation night, as a baseline evaluation; children with OSAS were recorded again after one year of RME treatment. Results After one year of treatment the OSAS group showed a longer duration of time in bed and sleep period time, a reduction in number of stage shifts compared to baseline recordings, and the apnea–hypopnea index decreased significantly. At baseline, the OSAS group had a higher CAP rate during slow-wave sleep and an increased A2 index compared to normal controls. After one year of RME application, children with OSAS showed an increase in CAP rate associated with an increase of A1 index during slow-wave sleep. Conclusions RME treatment almost normalized sleep architecture and improved sleep respiratory disturbances; however, sleep microstructure and respiratory parameters did not completely recover. The persistence of increased CAP rate in slow-wave sleep associated with an increase of A1 index might reflect a partial failure of orthodontic treatment. On the other hand, the rebound of A1 subtypes might be an indirect sign of an attempt to normalize sleep that has been disturbed by the respiratory events.

An altered autonomic control and response to respiratory events during sleep have been reported in infants with obstructive sleep apnea but appropriate methods are not established. We assessed the feasibility of pulse transit time (PTT) in detecting subcortical arousals in eight infants (median age 7 days) suffering from the Pierre Robin sequence and obstructive sleep apnea. Sleep studies including recordings of PTT performed before and after successful orthodontic treatment for their OSA were analyzed. PTT arousals (i.e., fall in PTT by ≥15 ms lasting for ≥3 s) were visually scored using specific analysis software. Apnea-related PTT arousals and spontaneous PTT arousals were distinguished and predicting factors for the occurrence of uninterpretable PTT signal and PTT arousals were analyzed. Six-hundred and seven apneas were analyzed. Uninterpretable PTT signal appeared in 394 (65%) apneas and were due to a disturbed pulse waveform in 63%. Predictors for the occurrence of uninterpretable PTT signal were type of apnea (odds ratio, 95% confidence interval for obstructive apnea = 0.5, 0.4–0.9) and duration of apnea (odds ratio, 95% confidence interval per second duration = 1.4, 1.3–1.5). Of 213 apneas with interpretable PTT signal, 43 (7% of all apneas) were followed by a PTT arousal. Predictor for their occurrence was treatment status (odds ratio, 95% confidence interval for pre-treatment status = 3.4, 1.3–8.8). Spontaneous PTT arousals during control periods appeared more frequently pre-treatment compared to post-treatment (41% vs. 16%; p-value = 0.001). There were only weak correlations between changes in PTT, heart rate, and arterial oxygen saturation (correlation coefficient

To evaluate NREM sleep instability, as measured by the cyclic alternating pattern (CAP), in children with sleep terrors (ST) vs. normal controls.Ten boys (mean age: 8.5 years, range 5-13) meeting the following inclusion criteria: (a) complaint of ST several times a month, (b) a history of ST confirmed by a third person, and (c) a diagnosis of ST according to the ICSD-2 criteria. Eleven age-matched control children with parental report of at least 8.5h of nightly sleep, absence of known daytime consequences of sleep disorders were recruited by advertisement from the community. Sleep was visually scored for sleep macrostructure and CAP using standard criteria.Sleep macrostructure showed only a significantly increased number of awakenings per hour and reduced sleep efficiency in ST subjects. CAP parameters analysis revealed several significant differences in ST vs. controls: an increase of total CAP rate in SWS, of A1 index in SWS and of the mean duration of A phases while B phases had a decreased duration, exclusively in SWS. The normalized CAP interval-distribution graphs showed significant differences in SWS with interval classes 10or = i35s higher in children with ST and intervals classes above 50s higher in normal controls.Children with ST showed faster alternations of the amplitude of slow EEG bursts during SWS. This abnormally fast alternation of the EEG amplitude in SWS is linked to the frequent intrusion of CAP B phases interrupting the continuity of slow delta activity and could be considered as a neurophysiological marker of ST.This abnormal alternation of the EEG amplitude in SWS is associated with the occurrence of parasomnias and might be considered as a neurophysiological marker of disorders of arousal.

Objective To analyze sleep architecture and NREM sleep alterations by means of the Cyclic Alternating Pattern (CAP) in children with Down syndrome (DS) and Fragile-X syndrome (fraX), the two most common causes of inherited mental retardation, in order to find out eventual alterations of their sleep microstructure related to their mental retardation phenotypes. Methods Fourteen patients affected by fraX (mean age 13.1 years) and 9 affected by Down syndrome (mean age 13.8 years) and 26 age-matched normal controls were included. All subjects underwent overnight polysomnography in the sleep laboratory, after one adaptation night and their sleep architecture and CAP were visually scored. Results FraX subjects showed a reduced time in bed compared to DS subjects, whereas DS subjects showed a lower sleep efficiency, a higher percentage of wakefulness after sleep onset, and a reduced percentage of stage 2 NREM compared to the other groups. Furthermore, DS and fraX subjects, compared to normal controls, showed a higher percentage of stage 1 NREM and a lower percentage of REM sleep. FraX subjects showed the most disrupted sleep microstructure with low total CAP rate and CAP rate in S2 NREM. Both patient groups showed a lower percentage of A1 and higher percentage of A2 and A3 compared to normal controls. Conclusions The analysis of CAP might be able to disclose new important findings in the sleep architecture of children with mental retardation and might characterize sleep microstructural patterns of the different phenotypes of intellectual disability. Significance The NREM sleep microstructure alterations found in our subjects, associated with the reduction in REM sleep percentage, seem to be distinctive features of intellectual disability.

Objective To evaluate sleep in children with autistic spectrum disorder (ASD) by means of sleep questionnaires and polysomnography; moreover, to analyze their cyclic alternating pattern (CAP). Methods Thirty-one patients with ASD (28 males, 3 females, aged 3.7–19 years) and age-matched normal controls were included. ASD children were evaluated by a standard sleep questionnaire that consisted of 45 items in a Likert-type scale covering several areas of sleep disorders and by overnight polysomnography in the sleep laboratory after one adaptation night. Results The questionnaire results showed that parents of ASD children reported a high prevalence of disorders of initiating and maintaining sleep, enuresis, repetitive behavior when falling asleep, and daytime sleepiness. Polysomnographically, ASD children showed reduced time in bed, total sleep time, sleep period time and rapid eye movement (REM) latency. ASD subjects had a CAP rate during slow-wave sleep (SWS) lower than normal controls, together with a lower percentage of A1 subtypes. Conclusions ASD children questionnaires showed a higher percentage of disorders of initiating and maintaining sleep than normal controls; this was not completely confirmed by sleep staging. CAP measures showed subtle alterations of NREM sleep which could be detected with an appropriate methodology of analysis. The reduction of A1 subtypes during SWS might play a role in the impairment of cognitive functioning in these subjects.

Study objectives To evaluate non-rapid eye movement sleep instability (NREM), as measured by the cyclic alternating pattern (CAP), in a cohort of children with attention-deficit/hyperactivity disorder (ADHD) and normal controls. Design Prospective study. Settings Sleep laboratory. Participants Twenty consecutive outpatients with ADHD (18 boys and 2 girls; age range 6-13 years, mean age 9.3 years) and 20 normal children matched for age and socioeconomic status underwent polysomnographic recordings for 2 consecutive nights in a standard laboratory setting. Sleep was visually scored for sleep macrostructure and CAP, according to standard criteria. Measurements and results Children with ADHD showed significantly reduced sleep duration and increased rate of stage shifts. All children with ADHD had an apnea-hypopnea index less than 1. Those with ADHD presented lower total CAP rates and lower CAP rates during sleep stage 2 than did normal controls. Moreover, in children with ADHD, we found a lower number of CAP sequences and a reduced total A1 index, mainly in light sleep (sleep stages 1 and 2). We did not find differences in A subtype percentages, but there was a longer duration of A1 subtypes in children with ADHD. Conclusions Children with ADHD showed a lower CAP rate and a lower number of CAP sequences; this supports the hypothesis of the existence of a hypoarousal state in these patients.

Objective The aim of this study was to evaluate the sleep breathing patterns and to detect the eventual presence of periodic leg movements (PLMs) in patients affected by Angelman syndrome (AS). Methods Ten children with AS were recruited to participate in the study; the clinical diagnosis was confirmed by the genetic analysis (maternal 15q deletion, uniparental paternal disomy, or mutation of the UBE3A gene). All patients but two had presented epileptic seizures. Two age-matched groups of patients with mental retardation (MR) associated (MRE+) or not (MRE−) to epilepsy were used as control groups. All subjects underwent one polysomnographic recording, after one adaptation night. Sleep stages were scored according to standard criteria slightly modified in order to take into account the specific EEG patterns of AS, also the apnea/hypopnea index (AHI) was quantified; PLMs were identified and the PLM index (PLMI) was computed. The statistical analysis was carried out by means of the one-way ANOVA, followed by the Fisher LSD post-hoc test, when appropriate, and by means of the linear correlation coefficient between AHI and PLMI. Results Sleep macrostructure showed only few significant differences between children with AS and the other two groups of subjects: AS patients showed higher percentage of wakefulness after sleep onset and sleep onset latency; moreover, the percentage of REM sleep was reduced in AS and in MRE+ subjects. A tendency for AS subjects to present a higher PLMI than the other two groups was also found. AHI >5 was found in 30% of AS subjects, in 30.8% of MRE+, and only in 20% of MRE− patients ( χ 2 =2.359, NS); 70% of AS patients, 38.5% of MRE+, and 46.7% of MRE− subjects had PLMI >5 ( χ 2 =3.088, NS). Conclusions These results confirm our previous questionnaire-based findings of a high prevalence of sleep breathing disorder and important PLMs in AS and allow us to hypothesize that epilepsy, rather than mental retardation, might exacerbate these sleep disorders. Significance Sleep breathing disorder and PLMs might contribute to the cognitive impairment and to the worsening of life quality of subjects with AS and with MR (mostly those with epilepsy). Therefore, our findings suggest the need to explore these sleep disorders in children affected by MR and to set up a correct treatment.

Objective NREM sleep patterns of narcoleptic patients with cataplexy were studied, focusing on their sleep ‘microstructure’, by analyzing the cyclic alternating pattern (CAP). Methods Forty-nine HLA DQB1*0602-positive patients with narcolepsy/cataplexy (32 men and 17 women, aged 18–46 years) were included together with 37 age-matched normal controls. Each subject underwent one polysomnographic night recording after an adaptation night. Sleep stages were scored following standard criteria and CAP A phases were detected and classified into 3 subtypes (A1, A2, and A3). Power spectra for frequencies between 0.5 and 25 Hz were obtained for each CAP condition, separately in sleep stage 2 and SWS. Results Narcoleptic patients displayed reduced total CAP rate. A selective reduction in the number of A1 subtypes/hour and a reduced A3 index were found in narcoleptics who had also a smaller average number of CAP sequences. Narcoleptic patients had higher power spectra for fast frequencies mostly during SWS, while REM sleep power spectra showed significantly higher power density for frequency bins 0.5–1.5, 8.5–9.5, and 17.5–25 Hz. Similarly, CAP A1 subtypes and NCAP epochs during SWS displayed significantly higher power density for fast frequency bins. Conclusions The main finding of this study is that the occurrence of the A1 CAP subtypes is impaired during NREM sleep in narcoleptic patients. Thus, narcolepsy seems to be accompanied not only by alterations of REM but also NREM sleep which is subtly but significantly impaired, as reflected by CAP and the corresponding EEG spectral analysis. Significance Our findings might indicate that in narcolepsy very-slow oscillation processes less effective than normal might be present, with a subtly impaired capability of grouping the other sleep EEG activities; this aspect deserves further insight in order to obtain a better understanding of its functional meaning.

Publisher Summary This chapter discusses scalp topography and cortical generators of the spectral components of the cyclic alternating pattern (CAP). The analysis of the so-called CAP, a phenomenon which is typical of non-rapid eye movement (NREM) sleep, has been previously confined to its first order time features and particular attention has been paid to its rate which is the percentage of each sleep stage occupied by CAP sequences. This type of approach has been conditioned by the common practice in sleep labs of including only a limited number of EEG channels in the polysomnographic recordings, because of the need of simplicity and the requirement of only one EEG channel by the internationally accepted rules of recording sleep. However, the significant advancements in computer technology of recent years now allow the recording and analysis of a large number of channels with limited additional effort. This allows us to have a better representation of the EEG over the scalp, also during sleep.

Objective To analyze in detail the frequency content of the different EEG components of the Cyclic Alternating Pattern (CAP), taking into account the ongoing EEG background and the nonCAP (NCAP) periods in the whole night polysomnographic recordings of normal young adults. Methods Sixteen normal healthy subjects were included in this study. Each subject underwent one polysomnographic night recording; sleep stages were scored following standard criteria. Subsequently, each CAP A phase was detected in all recordings, during NREM sleep, and classified into 3 subtypes (A1, A2, and A3). The same channel used for the detection of CAP A phases (C3/A2 or C4/A1) was subdivided into 2-s mini-epochs. For each mini-epoch, the corresponding CAP condition was determined and power spectra calculated in the frequency range 0.5–25 Hz. Average spectra were obtained for each CAP condition, separately in sleep stage 2 and SWS, for each subject. Finally, the first 6 h of sleep were subdivided into 4 periods of 90 min each and the same spectral analysis was performed for each period. Results During sleep stage 2, CAP A subtypes differed from NCAP periods for all frequency bins between 0.5 and 25 Hz; this difference was most evident for the lowest frequencies. The B phase following A1 subtypes had a power spectrum significantly higher than that of NCAP, for frequencies between 1 and 11 Hz. The B phase after A2 only differed from NCAP for a small but significant reduction in the sigma band power; this was evident also after A3 subtypes. During SWS, we found similar results. The comparison between the different CAP subtypes also disclosed significant differences related to the stage in which they occurred. Finally, a significant effect of the different sleep periods was found on the different CAP subtypes during sleep stage 2 and on NCAP in both sleep stage 2 and SWS. Conclusions CAP subtypes are characterized by clearly different spectra and also the same subtype shows a different power spectrum, during sleep stage 2 or SWS. This finding underlines a probable different functional meaning of the same CAP subtype during different sleep stages. We also found 3 clear peaks of difference between CAP subtypes and NCAP in the delta, alpha, and beta frequency ranges which might indicate the presence of 3 frequency components characterizing CAP subtypes, in different proportion in each of them. The B component of CAP differs from NCAP because of a decrease in power in the sigma frequency range. Significance This study shows that A components of CAP might correspond to periods in which the very-slow delta activity of sleep groups a range of different EEG activities, including the sigma and beta bands, while the B phase of CAP might correspond to a period in which this activity is quiescent or inhibited.

Objective To assess inter-rater reliability between different scorers, from different qualified sleep research groups, in scoring visually the Cyclic Alternating Pattern (CAP), to evaluate the performances of a new tool for the computer-assisted detection of CAP, and to compare its output with the data from the different scorers. Methods CAP was scored in 11 normal sleep recordings by four different raters, coming from three sleep laboratories. CAP was also scored in the same recordings by means of a new computer-assisted method, implemented in the Hypnolab 1.2 (SWS Soft, Italy) software. Data analysis was performed according to the following steps: (a) the inter-rater reliability of CAP parameters between the four different scorers was carried out by means of the Kendall W coefficient of concordance; (b) the analysis of the agreement between the results of the visual and computer-assisted analysis of CAP parameters was also carried out by means of the Kendall W coefficient; (c) a ‘consensus' scoring was obtained, for each recording, from the four scorings provided by the different raters, based on the score of the majority of scorers; (d) the degree of agreement between each scorer and the consensus score and between the computer-assisted analysis and the consensus score was quantified by means of the Cohen's k coefficient; (e) the differences between the number of false positive and false negative detections obtained in the visual and in the computer-assisted analysis were also evaluated by means of the non-parametric Wilcoxon test. Results The inter-rater reliability of CAP parameters quantified by the Kendall W coefficient of concordance between the four different scorers was high for all the parameters considered and showed values above 0.9 for total CAP time, CAP time in sleep stage 2 and percentage of A phases in sequence; also CAP rate showed a high value (0.829). The most important global parameters of CAP, including total CAP rate and CAP time, scored by the computer-assisted analysis showed a significant concordance with those obtained by the raters. The agreement between the computer-assisted analysis and the consensus scoring for the assignment of the CAP A phase subtype was not distinguishable from that expected from a human scorer. However, the computer-assisted analysis provided a number of false positives and false negatives significantly higher than that of the visual scoring of CAP. Conclusions CAP scoring shows good inter-rater reliability and might be compared in different laboratories the results of which might also be pooled together; however, caution should always be taken because of the variability which can be expected in the classical sleep staging. The computer-assisted detection of CAP can be used with some supervision and correction in large studies when only general parameters such as CAP rate are considered; more editing is necessary for the correct use of the other results. Significance This article describes the first attempt in the literature to evaluate in a detailed way the inter-rater reliability in scoring CAP parameters of normal sleep and the performances of a human-supervised computerized automatic detection system.

Background and purpose The aim of this study was to define quantitatively the spectrum content of the sleep pattern termed ‘cyclic alternating pattern’ (CAP) A phases, their scalp topography and their probable cortical generators, by using data from sleep polygraphic recordings that included a large number of scalp EEG channels. Patients and methods Polysomnographic recording that include 19 EEG channels were obtained from 5 normal healthy young controls. After sleep staging, for each subject, 5 different CAP A phase subtype epochs were selected, which served for subsequent analysis. Following the analysis of power spectra calculated on the C4 channel by means of the fast Fourier transform, two different frequency bands were detected: 0.25–2.5 and 7–12 Hz, representing the frequency peak in the profiles of the different CAP subtypes. All the subsequent analyses were performed on these two bands. Scalp topographic color mapping was carried out using the data from all the 19 EEG channels recorded, and by means of the 4-nearest neighbor algorithm. Individual average maps were obtained for both frequency bands. Finally, we used the low resolution brain electromagnetic tomography (LORETA) functional imaging for the source analysis of the two EEG frequency components of CAP A phases. Results The quantitative spectral analysis of the different A phase subtypes shows the existence of two distinct spectral components characterizing CAP subtypes A1 (0.25–2.5 Hz) and A3 (7–12 Hz). These two components coexist in CAP A2 subtypes. The topography of these two components shows a clear prevalence over the anterior frontal regions for the 0.25–2.5 Hz band and over the parietal–occipital areas for the 7–12 Hz band. Finally, the generators of the low-frequency component of CAP seemed to be localized mostly over the frontal midline cortex; on the contrary, those of the high-frequency band involved both midline and hemispheric areas within the parietal and occipital areas. Conclusions The results of this study confirm the presence of two fundamentally distinct frequency bands which are expressed individually (A1 and A3) or in association (A2) in the different CAP A phase subtypes. The analysis of scalp distribution maps indicates that the two frequency components recognized are distributed over clearly different areas of the scalp. Moreover, the LORETA analysis indicates that also the probable cortical generators of these two frequency bands are different and well separated and distinct.

To test the hypothesis that the administration of l -5-hydroxytryptophan ( l -5-HTP) might exert beneficial effects on sleep terrors, we carried out an open pharmacological trial in a group of children with sleep terrors compared to a group of children with the same disorder but without l -5-HTP treatment. Participants in the trial were 45 children (34 males and 11 females; age range 3.2–10.6 years), referred to the Sleep Centre of the Department of Developmental Neurology and Psychiatry of the University of Rome “La Sapienza”, affected by sleep terrors. All subjects underwent: (1) complete medical and sleep history; (2) complete neurological examination and EEG recording whilst awake and sleeping, (3) a structured sleep diary for 2 months, (4) after 1 month, all subjects were examined again from the clinical and EEG points of view and (5) after 6 months, a structured interview in order to evaluate the clinical outcome. After the first visit, l -5-HTP was administered (2 mg/kg per day) at bedtime to 31 randomly selected patients for a single period of 20 consecutive days. After 1 month of treatment, 29/31 (93.5%) of patients showed a positive response. In the comparison group without drug therapy, after 1 month, the episodes disappeared only in four children (28.6%) while ten children (71.4%) showed the persistence of episodes with the same frequency as before. After 6 months, 26/31 (83.9%) of children treated with l -5HTP were sleep terror-free, while in five children (16.1%) sleep terror episodes persisted. Of the children in the comparison group, ten (71.4%) continued to show sleep terrors at 6-month follow-up. Conclusion:to our knowledge, this is the first study demonstrating the efficacy of a new drug treatment for sleep terrors. These results confirm our initial hypothesis and represent evidence that treatment with l -5-hydroxytryptophan is able to modulate the arousal level in children and to induce a long-term improvement of sleep terrors.

Only few studies are available on sleep disorders in Angelman syndrome (AS), a neurodevelopmental disorder with several behavior disturbances. The aim of this study was to determine the prevalence of sleep disorders in a relatively large group of AS subjects, compared to that of age-matched controls. Forty-nine consecutive parents of patients with AS (26 males and 23 females aged 2.3-26.2 years) were interviewed and filled out a comprehensive sleep questionnaire. Based on their genetic etiology, four groups were defined: deletion of chromosome 15q11-13 (25 subjects); methylation imprinting mutation (six subjects), UBE3A mutations (seven subjects) and paternal uniparental disomy (five subjects). In the remaining cases genetic testings were negative. A significantly high frequency of disorders of initiating and maintaining sleep, prolonged sleep latency, prolonged wakefulness after sleep onset, high number of night awakenings and reduced total sleep time were found in our AS patients, as compared to age-matched controls. We also found other types of sleep disorders, never reported before, such as enuresis, bruxism, sleep terrors, somnambulism, nocturnal hyperkinesia, and snoring. No differences were found between the four genetic aetiology groups. Moreover, we did not find important improvement of sleep disturbances from pre-pubertal to post-pubertal ages. Our data confirm the significant presence of sleep/wake rhythms fragmentation, peculiar of AS, and also demonstrate the presence of several other types of sleep disturbances in this syndrome.

Objectives : To evaluate cyclic alternating pattern (CAP) in sleep of school-age children in order to obtain a standardized database for CAP parameters in this age range. Methods : CAP parameters were quantified in 10 normal healthy subjects (6 males and 4 females, mean age 8.3 years; range 6–10 years). All subjects underwent polysomnography recordings for two consecutive nights in a standard laboratory setting. Sleep data were stored on computer using a 16-channel polysomnography digital system. Sleep macrostructure was visually scored according to the criteria by Rechtschaffen and Kales (Brain Information Service/Brain Research Institute, University of California, Los Angeles, 1968); CAP was visually scored following the criteria by Terzano et al. (Sleep Med 2 (2001) 537). Results : CAP rate showed a progressive increase with the deepness of sleep, with high values during slow wave sleep (SWS). CAP time showed its longest duration during non-REM (NREM) sleep stage 2 (S2), followed by SWS and sleep stage 1 (S1). No differences across NREM sleep stages were found for CAP cycle and phase B mean duration; on the contrary, phase A showed longer duration during SWS than in S1 and S2. Phases A1 were the most numerous (84.45%) followed by A3 (9.14%) and by A2 (6.44%). The distribution of phases A subtypes across NREM stages showed significant differences for the A1 subtypes that occurred more frequently during SWS than in S2 and S1 (and during S2 than in S1). Subtypes A3 were more frequent during S1 than SWS while no differences were found for subtype A2. The analysis of A1 interval distribution showed a log-normal-like distribution with a peak around 25 s for the A1 phases and no clear peak for A2–A3 phases. Conclusions : The analysis of CAP in school-age children is characterized by an increase of CAP rate during SWS and a high percentage of A1 phases. The distribution of interval between consecutive A1 phases showed a peak around 25 s.

Pediatric insomnia is an extrinsic sleep disorder subdivided into two categories: behavioral insomnia and insomnia related to medical, neurological, and psychiatric diseases. This review will cover several types of insomnia, comorbidities and specific pediatric therapies according to clinical characteristics and age. Behavioral insomnia should be differentiated from pediatric insomnia due to medical conditions, mostly occurring during the first year of life. Multiple night awakenings and diurnal hypersomnolence are strong indicators of insomnia due to medical conditions. Insomnia during adolescence and pediatric insomnia associated with psychiatric comorbidity, cognitive disabilities and epilepsy, will be discussed in terms of diagnosis, clinical features and implications for treatment.

Publisher Summary 10–15% of preschool children suffer from mild to moderate behavioral problems. This prevalence has been confirmed by studies using different scales. Such studies show that poor sleepers' preschool children undergo a very high rate of behavior problems. The direction of this relationship is difficult to evaluate. Sleep disturbances could be a significant early childhood symptom of later behavioral problems. Several studies support this hypothesis: sleep disorders at three years of age are significant predictors of internalizing problems and overall behavior disturbances at six years; in a high-risk behavior group of three-year-old children the predictive variables at three months are restless sleep and bedtime difficulties; sleep problems are a significant early childhood symptom of later problems. Early behavioral problems are associated with later sleep disturbances. This second hypothesis is supported by the observation that 50% of eight-year-old children with sleep disorders show an association with behavioral problems at preschool age. This chapter analyzes the relationships between night awakenings, bedtime resistance and/or sleep problems with daytime behavior disturbances and parenting style.

INTRODUCTION. We present a series of children who underwent a video-polysomnographic recording at our Sleep and Epilepsy Unit, who received a diagnosis of nocturnal frontal lobe epilepsy (NFLE). AIMS. To describe electroclinical and video polygraphic features of paediatric NFLE that differentiate this condition from other sleep disorders that overlap and mimic the sleep motor and autonomic events of NFLE. PATIENTS AND METHODS. The inclusion criterion was that the patients have their first video-EEG-PSG recording in our laboratory. RESULTS. Twenty-four out of 190 children were diagnosed with NFLE (group 1); while 166 had other sleep disorders (group 2). Among children diagnosed with NFLE, seven were referred for sleep-disordered breathing, seven for parasomnias, two for insomnia, two for hypersomnia, and one for periodic limb movements, while five were referred for epilepsy. In group 1, perinatal history was normal in most cases (21 out of 24) and a familiar history of epilepsy was found in four cases. Sleep-disordered breathing was diagnosed as a comorbid condition in four children. Standard EEG was normal in 21 cases. Interictal EEG showed epileptic discharges in four cases, while ictal EEG was expressed by a rhythmic theta activity preceded by an arousal and/or a short background desynchronization, movement artifacts, and autonomic changes. All seizures, repeated highly stereotyped motor events, were followed by stage shifts and/or a postural change and, by short awakenings. CONCLUSIONS. We found a high percentage of children with NFLE, often misdiagnosed or associated with other sleep disorders, which may be a trigger for nocturnal seizures.