Silvia Miano

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). Management of obstructive sleep disordered breathing in childhood should follow a stepwise approach http://ow.ly/SdKwD

Sleep phenotypes of intellectual disability: a polysomnographic evaluation in subjects with Down syndrome and Fragile-X syndrome.

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.

Sleep disturbances in Angelman syndrome : a questionnaire study

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.

Sleep cyclic alternating pattern in normal school-age children

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.

The relationship between sleep and epilepsy: the effect on cognitive functioning in children

Aim  The purpose of this review was to examine the possible pathophysiological links between epilepsy, cognition, sleep macro‐ and microstructure, and sleep disorders to highlight the contributions and interactions of sleep and epilepsy on cognitive functioning in children with epilepsy.

Melatonin to prevent migraine or tension-type headache in 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.

Epidemiology and Management of Insomnia in Children with Autistic Spectrum Disorders

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.

Neurocognitive assessment and sleep analysis in children with sleep-disordered breathing

OBJECTIVE To assess possible correlations between intelligence quotient (IQ) and attention deficit hyperactive disorder (ADHD) rating scale values and sleep (including cyclic alternating patterns analysis) and respiratory parameters in children with sleep-disordered breathing (SDB). METHODS Thirteen children who satisfied the criteria for primary snoring and 31 children for obstructive sleep apnea syndrome (OSAS) underwent polysomnography in a standard laboratory setting and a neurocognitive assessment. Sixty normal controls recruited from two schools underwent the neurocognitive assessment. RESULTS The IQ estimates of controls were higher and the ADHD rating scale scores lower than those of children with SDB. Children with OSAS had a higher REM sleep latency and arousal index as well as a lower N3 and A mean duration than children who snored. In our sample of children with SDB, the percentage of wakefulness after sleep onset, of N1, of A2, of arousal and A2 index correlated positively with global intelligence. Total and hyperactivity scores correlated positively with the A2 index. Regression analysis mostly confirmed the correlations between neurocognitive measures and sleep parameters and further demonstrated a negative correlation between the hyperactivity rating score and oxygen saturation during the night. CONCLUSIONS Our results support the hypothesis that arousal is a defensive mechanism that may preserve cognitive function by counteracting the respiratory events, at the expense of sleep maintenance and NREM sleep instability. SIGNIFICANCE We believe that our study makes an interesting contribution to research on the relationship between sleep fragmentation and cognitive function.

All-night EEG power spectral analysis of the cyclic alternating pattern components in young adult subjects

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 6h 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.

NREM sleep instability in children with sleep terrors: The role of slow wave activity interruptions

OBJECTIVE To evaluate NREM sleep instability, as measured by the cyclic alternating pattern (CAP), in children with sleep terrors (ST) vs. normal controls. METHODS 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. RESULTS 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 10< or = i < 35s higher in children with ST and intervals classes above 50s higher in normal controls. CONCLUSIONS 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. SIGNIFICANCE 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.