A preliminary study of sleep spindles across non-rapid eye movement sleep stages in children with autism spectrum disorder.

Study Objectives: Sleep spindles play a crucial role in multiple neuronal network functions. Initiation and termination of spindles are regulated by the thalamic reticular nucleus and thalamocortical network, and the spindle can be an index for brain organization. We conducted a preliminary study of the parameters of sleep spindles, focusing on sleep-stage temporal distribution in children with autism spectrum disorder (ASD) with normal intelligence/developmental quotients. Methods: We performed overnight polysomnography in 14 children with ASD (4-10 years) with normal full-scale intelligence quotient/developmental quotient (≥75) and 14 community samples (CS) of children. Sleep stages were scored according to the Rechtschaffen and Kales criteria. Spindle parameters were quantified and compared between these groups and the identified subgroups. Results: Sleep parameters did not differ between the ASD and CS groups, except for a higher rate of rapid eye movement (REM) sleep duration in ASD. Spindle parameters did not significantly differ between the groups, but spindle density was distributed in a broader range in the ASD group. Five children with ASD had a higher spindle density in stage 3 than in stage 2. The ratio of spindle density in stage 3 to that in stage 2 (stage 3/2 ratio) was significantly higher in ASD than in CS cases. Conclusions: The lower spindle density in stage 2 and relatively higher density in stage 3 in children with ASD may represent an abnormal generation of spindles due to insufficient maturation of the thalamic reticular nucleus and thalamocortical network.

An Interactive Smartphone App, Nenne Navi, for Improving Children's Sleep: Pilot Usability Study.

BACKGROUND: Healthy sleep is important not only for physical health but also for brain development in children. Several reports have revealed that Japanese adults and children have later bedtimes and shorter sleep durations compared with those in other countries, possibly because of Japanese culture and lifestyles. Therefore, an intervention tool that is suitable to the Japanese sociocultural environment is urgently needed to improve children's sleep problems in their early years. OBJECTIVE: To provide appropriate sleep health literacy to caregivers and change their parenting behavior, we developed a smartphone app that allows reciprocal interaction between caregivers and pediatric sleep experts. This paper describes a preliminary study to examine the app's basic design and functions and to establish its acceptability and usability in a small sample. METHODS: A total of 10 caregivers and 10 infants (aged 18-28 months; 4/10, 40% boys) living in Japan participated in the study. At the start of the trial, the e-learning content regarding sleep health literacy was delivered via a smartphone. Thereafter, caregivers manually inputted recorded data about their own and their infant's sleep habits for 8 consecutive days per month for 2 months. After pediatric sleep experts retrieved this information from the Osaka University server, they specified the problems and provided multiple sleep habit improvement suggestions to caregivers. Caregivers then selected one of the feasible pieces of advice to practice and reported their child's sleep-related behaviors via the app. Actigraphy was used to monitor children's sleep behaviors objectively. The concordance between the information provided by caregivers and the actigraphy data was assessed. The acceptability and usability of the app were evaluated using self-report questionnaires completed by caregivers; qualitative feedback was obtained via semistructured interviews after the intervention. RESULTS: There was no significant difference between the information provided by the caregivers and the actigraphy data for bedtimes and wake-up times (P=.13 to P=.97). However, there was a difference between the actigraphy data and the caregivers' reports of nighttime sleep duration and nighttime awakenings (P<.001 each), similar to prior findings. User feedback showed that 6 and 5 of the 10 caregivers rated the app easy to understand and easy to continue to use, respectively. Additionally, 6 of the 10 caregivers rated the app's operativity as satisfactory. Although this was a short-term trial, children's sleep habits, caregivers' sleep health consciousness, and parenting behaviors improved to some extent. CONCLUSIONS: The present findings suggest that the app can easily be used and is acceptable by Japanese caregivers. Given the user feedback, the app has the potential to improve children's sleep habits by sending individualized advice that fits families' backgrounds and home lives. Further studies are needed to confirm the efficacy of the app and facilitate social implementation.

Evaluation of the validity of psychological preparation for children undergoing polysomnography.

STUDY OBJECTIVES: Nocturnal polysomnography (PSG) is an essential diagnostic technique to assess sleep abnormalities, including sleep-disordered breathing (SDB). Although low in invasiveness, it is extremely difficult to conduct PSG with children who are not cooperative with wearing electrodes and sensors. Particularly, it is difficult to conduct PSG on children with autism spectrum disorder (ASD) because they have poor predictive ability, exhibit extreme anxiety about novel and unfamiliar things, and have difficulty understanding verbal instructions. Recently, the usefulness of psychological preparation was reported. The primary aim of this study was to assess the usefulness of psychological preparation for PSG. METHODS: The goal of our study was to assess the usefulness of psychological preparation for PSG. A total of 253 children were enrolled in the study: 131 in the control group (19 with ASD) and 122 selected for psychological preparation (51 with ASD). RESULTS: In the preparation group, 110 of 122 (90.2%) could undergo regular PSG, a significantly higher percentage than the control group at 104 of 131 (79.4%), P = .018. Regarding hypnotic drugs, in the preparation group 111 of 122 (91.0%) underwent PSG without hypnotic drugs, which was a significantly higher percentage than in the control group at 107 of 131 (81.7%), P = .032. Additionally, 45 of 51 children with ASD in the preparation group (88.2%) could undergo PSG without hypnotic drugs. CONCLUSIONS: This study indicated that psychological preparation was effective in facilitating PSG without hypnotic drugs in children who have difficulty cooperating with PSG, including those with ASD.

Japanese Sleep Questionnaire for Elementary Schoolers (JSQ-ES): validation and population-based score distribution.

OBJECTIVE: The Japanese Sleep Questionnaire for Elementary Schoolers (JSQ-ES) was developed to measure the sleep habits and disturbances of Japanese children. The current study aimed to present psychometric properties and describe the score distribution of the JSQ-ES. In addition, it examined correlations between the sleep and daytime behavior of school-aged children. METHOD: Guardians of 4369 elementary school children and 100 children diagnosed with sleep disorders in two clinics completed the JSQ-ES. RESULTS: Exploratory factor analysis and confirmatory factor analysis suggested a nine-factor structure. The JSQ-ES internal consistency was 0.876 and 0.907 for the community and clinical groups, respectively. Score distribution differences were observed between the two groups. A cut-off point of 80 was identified for the total JSQ-ES score. CONCLUSIONS: Exploratory factor analysis and confirmatory factor analysis suggested a nine-factor structure: (1) restless legs syndrome; (2) sleep-disordered breathing; (3) morning symptoms; (4) nighttime awakenings; (5) insomnia; (6) excessive daytime sleepiness; (7) daytime behavior; (8) sleep habits; and (9) irregular/delayed sleep phase. The study verified that the JSQ-ES is a valid and reliable instrument with which to evaluate Japanese sleep habits using a large population-based sample. The JSQ-ES may be useful in both clinical and academic settings.

Evaluation of behavioral change after adenotonsillectomy for obstructive sleep apnea in children with autism spectrum disorder.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) may affect daily cognitive functioning in children. The aims of our study were two-fold. The first aim was to detect, using the Child Behavior Checklist (CBCL), whether adenotonsillectomy (AT) for the treatment of OSA improved the behavior of children with autism spectrum disorder (ASD). The second aim was to identify characteristics for behavioral improvement following the treatment of OSA in these children with ASD. METHODS: The behaviors of ASD children aged 5-14 years diagnosed as having OSA (n=30) were evaluated using CBCL before and after AT. CBCL evaluation of ASD children without OSA at two time points with the same interval served as a control (n=24). We statistically examined the two groups. In addition, we conducted a paired t-test to assess changes in CBCL Tscores between the improved group and unchanged/deteriorated group to identify characteristics that may affect behavioral changes following OSA treatment. RESULTS: After AT, T-scores of the CBCL scales were significantly improved in the OSA group, but no change was observed in the control. A paired t-test revealed that the improved group had significantly higher scores on the CBCL pre-AT than the unchanged/deteriorated group in ASD children with OSA after OSA treatment. CONCLUSIONS: Behavioral problems were significantly improved following AT in ASD children with OSA. Early detection and treatment of children with OSA is essential to prevent behavioral problems and to support mental development.

Sleep problems are more frequent and associated with problematic behaviors in preschoolers with autism spectrum disorder.

BACKGROUND: Children with autism spectrum disorder (ASD) often suffer from sleep problems that in turn correlate with behavioral problems. However, in Japan, there have been few studies of sleep problems in children with ASD. AIMS: This study compared sleep problems in preschoolers from the community and preschoolers with ASD in Japan, and examined whether sleep problems were related to problematic behaviors in ASD preschoolers. METHODS AND PROCEDURES: Sleep problems were assessed in 965 community and 193 ASD preschoolers using the Japanese Sleep Questionnaire for Preschoolers, which was developed to assess sleep problems in Japanese preschoolers. Behavioral problems were assessed in 107 ASD preschoolers using the Child Behavior Checklist. OUTCOMES AND RESULTS: Compared with community preschoolers, ASD preschoolers experienced significantly more sleep problems, including obstructive sleep apnea and parasomnias. ASD preschoolers with sleep problems exhibited more behavioral problems than those without sleep problems. The severity of sleep problems, especially insomnia, was significantly correlated with behavioral problems in ASD preschoolers. CONCLUSIONS AND IMPLICATIONS: The present study suggests that sleep problems, especially obstructive sleep apnea, are more common in ASD preschoolers than in community preschoolers. The study also shows that sleep problems, especially insomnia, are related to problematic behavior in ASD preschoolers.

Psychometric properties and population-based score distributions of the Japanese Sleep Questionnaire for Preschoolers.

OBJECTIVE: We aimed to present psychometric properties and describe the score distributions of the Japanese Sleep Questionnaire for Preschoolers (JSQ-P), a guardian-reported survey questionnaire for assessing sleep disturbances and problematic sleep habits among preschool children. METHODS: Guardians of 2998 toddlers in three communities and guardians of 102 patients diagnosed with sleep disorders in two clinics completed the JSQ-P. RESULTS: Exploratory factor analysis (EFA) revealed the 10 domains of the JSQ-P to be similar to our previous small-scale study and confirmed the robustness of the JSQ-P. The JSQ-P showed acceptable internal consistency; α coefficients ranged from 0.622 (insufficient sleep) to 0.912 (restless legs syndrome [RLS], motor) for the community sample and 0.696 (insufficient sleep) to 0.959 (RLS, motor) for the clinical sample. The score differentiations between the community and clinical samples associated with RLS, obstructive sleep apnea syndrome (OSAS), morning symptoms, parasomnias, excessive daytime sleepiness, and daytime behaviors were demonstrated in our study. The distributions of percentile T scores for each subscale and age and gender differentiation of scores also were evaluated. CONCLUSIONS: We confirmed that the JSQ-P is a valid and reliable instrument to evaluate Japanese sleep habits using a large population-based sample. The JSQ-P may be useful in both clinical and academic settings.

Evaluation of oral iron treatment in pediatric restless legs syndrome (RLS).

OBJECTIVE: We conducted a retrospective chart review of children with restless legs syndrome (RLS) to evaluate the efficacy of oral iron treatment, which was administered open-label during the course of clinical care. In addition, we provided detailed clinical information about RLS in this pediatric cohort. PATIENTS AND METHODS: The study included 30 consecutive Japanese children with RLS who visited the Pediatric Sleep Clinic at Osaka University Hospital, and consisted of 17 boys and 13 girls, aged 2-14 years (mean ± SD, 6.5 ± 2.8). All-night polysomnography was performed in 18 patients and serum ferritin levels were measured in all the patients. After the diagnosis of RLS, iron was administered at doses between 1.6 and 7.8 mg/kg/day (3.2 ± 1.3). Serum ferritin was re-evaluated 3-6 months after iron treatment, or when RLS symptoms had disappeared. RESULTS: The patient age at onset of RLS symptoms ranged from six months to 13 years (4.3 ± 3.6). A positive family history was recognized in 19 children (63.3%). Serum ferritin levels before therapy were 9-62 ng/ml (26.6 ± 12.8) and oral iron supplementation was reported to be highly effective in 17 children, effective in 10, and ineffective in three. The serum ferritin level at follow-up was 23-182 ng/ml (83.5 ± 49.8). The onset of treatment effect was within approximately three months. CONCLUSIONS: Iron treatment could be effective in Japanese pediatric RLS.

Sleep problems in physically disabled children and burden on caregivers.

AIM: The present study was implemented to investigate relationships between sleep problems in physically disabled children and sleep quality and perceived burden of caregivers. METHODS: Subjects comprised 100 caregivers of disabled children, including 96 mothers, 2 fathers and 2 grandmothers. Questionnaires included demographic data for children and caregivers, sleep problems of children, and sleep quality (Pittsburgh sleep quality index (PSQI)) and perceived burden on caregivers (Japanese version of the Zarit Burden Interview (J-ZBI)). The sleep problems of children were evaluated according to the following five categories: "Problems initiating and maintaining sleep"; "Problems with sleep-related breathing"; "Problems with excessive somnolence"; "Problems with circadian rhythm"; and "Problems with sleep-related movement". RESULTS: The children comprised 66 boys and 34 girls (age range, 1-17 years). Of these, 65 children could not sit up and 35 could. A total of 88 children were found to have one or more categories of sleep problems. The most common sleep problem was "Problems initiating and maintaining sleep" (64.8%), followed by "Problems with sleep-related movement" (59.1%). J-ZBI was significantly higher in caregivers of children with "Problems initiating and maintaining sleep". PSQI scores were significantly higher in caregivers of children with "Problems with sleep-related breathing" and "Problems with circadian rhythm". A significant correlation was identified between perceived J-ZBI and PSQI of the caregiver. CONCLUSIONS: Increased focus on the sleep problems of disabled children is needed, particularly in relation to the sleep quality and perceived burden of caregivers.

[Deficiency of REM sleep in a patient with pontine cavernous hemangioma].

A 15-year-old girl had no REM sleep presumably due to a pontine cavernous hemangioma was reported. Her brain MRI revealed a cavernous hemangioma extending from the dorsal pontine to the medulla. She manifested truncal ataxia, facial nerve palsy, and ocular motor apraxia. She could not sleep in the supine position due to the sleep apnea accompanied with loud snoring. Overnight polysomnography (PSG) was performed for detection of obstructive sleep apnea syndrome (OSAS). In addition to severe OSAS and Cheyne-Stokes-like respiration at wake after sleep onset, her 1st PSG study revealed no periods with rapid eye movement, EEG characteristic of REM sleep, atonia and variation on respiratory and heart rate. Even after effective therapy for OSAS with non-invasive positive airway pressure ventilation (NPPV), her 2nd PSG also failed to show stage REM. These findings suggest that this pontine cavernous hemangioma disturbed her REM-on system. This is the first report of an individual with long-term loss of REM sleep and a valuable case for the understanding of anatomical structures of the REM-on system and the role of REM in memory consolidation.

Sleep disordered breathing in childhood-onset acid maltase deficiency.

OBJECTIVES: To clarify the feature of sleep disordered breathing (SDB) associated with childhood-onset acid maltase deficiency (AMD): the progressive nature of SDB and the stage of AMD. STUDY DESIGN: We retrospectively studied 4 patients with childhood-onset AMD by analyzing the results of neurological examinations for muscle wasting and muscle strength and the data on venous gas and from a pulmonary function test and nocturnal polysomnography (PSG). RESULTS: Three out of the 4 patients showed muscular symptoms including myalgia, lordoscoliosis, muscle wasting and muscle weakness. They also complained of sleep-related symptoms such as tiredness in the morning and daytime sleepiness. All of them showed SDB by PSG, even in a patient in the earliest stage who exhibited no signs or symptoms of muscle weakness. In 3 patients, noninvasive intermittent positive pressure ventilation during sleep was introduced; and thereafter sleep-related symptoms were resolved and no lower respiratory infection reoccurred. Although their quality of life was improved, no improvement of respiratory function was shown by spirometry over a 2-year follow-up period. CONCLUSIONS: SDB seems to be common in childhood-onset AMD, which is not always accompanied by daytime muscular symptoms, especially in mild patients. PSG should be utilized for detecting SDB, which could be one of the earliest signs of respiratory muscle involvement in childhood-onset AMD.

[Restless-leg syndrome--possible unrecognized cause for insomnia and irritability in children].

Restless legs syndrome (RLS) has gradually been recognized as a cause for insomnia in adults, but there have been few reports about children with RLS in Japan. Here we described seven pediatric RLS patients. All of the parents of our patients had difficult times to make their children sleep due to irritability, restlessness, and demanding bedtime routines. All patients had asked their parents to rub their feet in bed, and it took more than half an hour to soothe them until they fell asleep. Their mothers had been exhausted from this night-time routine. However, they did not consider the routine abnormal, as it had been their habitual behavior since infancy. Some parents were too distressed or embarrassed to describe the symptoms of their child properly. Five patients had clear family history and none had obvious periodic leg movements during sleep. All patients showed low levels of ferritin and iron supplementation was effective in five cases. In the severest two cases, pramipexole, but not iron, was dramatically effective. Both patients started to show RLS symptoms in the early days of infancy, which may suggest more severe hereditary dopaminergic dysfunction. RLS does occur in childhood and pediatricians should bear it in mind as one of the differential diagnoses when seeing children who are irritated and/or having difficulty in initiating their sleep.

Examination of non-restrictive and non-invasive sleep evaluation technique for children using difference images.

In recent years, the inappropriate sleep style for children has become known as one of the important causes of behavioral disorders, for example inattentiveness during waking hours or hyperactivity. Consequently, screening for the children having sleep disorders is needed to treat in the early stage of the behavioral disorders. From the point of view of evaluation for children's sleep, there are three problems. First, the conventional polysomnogram (PSG) requires great investment in facility and high personnel cost so that hospitals equipped with the PSG examination are rare. Next, the sleep-check examination system such as PSG and so on requires many sensors to be attached to the client's face and body. So the client feels suffering severe stress and the wires of sensors trigger some accidents. At last, it is very difficult to get ordinary sleep style in the sleep examination room because of above factors. It is strongly desirable to develop a new method of sleep evaluation system in place of conventional PSG that is non-restrictive and non-contact. Taking these problems into account, we devised a technique with these characteristics that is completely separated from sensors. It determines the sleep condition from body movement information by measuring movements using difference processing of video image. Our study of using this technique on pediatric patients indicated that this non-restrictive technique could be effective for evaluating body movement during sleep. It was looked for a relationship between movements information and sleep conditions.

Long-term hospitalization during pregnancy is a risk factor for vitamin D deficiency in neonates.

In order to examine the effects of long-term hospitalization during pregnancy on vitamin D metabolism in pregnant women and neonates, we measured the serum 25-hydroxyvitamin D (25OHD) levels in pregnant women, as well as measuring 25OHD levels in cord blood and breast milk. In pregnant women hospitalized for longer than 1 month, the serum 25OHD levels were decreased at delivery compared with those in control subjects (10.9 +/- 2.6 ng/l vs 19.5 +/- 4.9 ng/l; P < 0.01). Although the levels of 25OHD in the cord blood were not significantly different between the long-term hospitalized and control pregnant women in this study (9.36 +/- 1.7 ng/l vs 11.1 +/- 3.0 ng/l), the 25OHD concentrations in the cord blood were significantly lower than the maternal levels in both groups; the ratios of the levels in cord blood to sera in the long-term hospitalized women and control subjects were 82.1% and 60.3%, respectively. Long maternal hospitalization does not always cause neonatal vitamin D deficiency, but could be one of its major risk factors. Therefore, sufficient sunlight exposure and intake of sufficient vitamin D are considered to be important to prevent vitamin D deficiency in long-term hospitalized pregnant women as well as their babies.

Shift of serum osteocalcin components between cord blood and blood at day 5 of life.

Vitamin K deficiency is a relatively common condition in neonates. However, the role of vitamin K in neonatal bone metabolism remains to be determined. Osteocalcin (OC) is the most abundant noncollagenous protein in bone, and is regulated to be gamma-carboxylated by vitamin K. In this study, we measured gamma-carboxylated osteocalcin (Gla-OC) and non- or undercarboxylated osteocalcin (Glu-OC) separately, and examined the effects of vitamin K on osteocalcin metabolism. Eighteen full-term healthy neonates were enrolled in this study. In the cord and d-5 blood samples, the OC levels were determined by three different methods to examine the intact OC by immunoradiometric assay (IRMA), Gla-OC, and Glu-OC. Serum vitamin K fractions, hepaplastin test, and type 1 procollagen carboxyl extension peptide were also determined. Urine samples were also collected from the first voiding and on d 5 to determine urinary pyridinoline, deoxypyridinoline, and gamma-carboxylated glutamic acid. Serum levels of phylloquinone (PK) and menaquinone (MK)-4 increased on d 5 following vitamin K administration and increased intake in breast milk and/or formula. The OC levels determined by IRMA did not change between cord and d-5 blood samples, but the Gla-OC level increased remarkably and Glu-OC reduced to a negligible level. OC in cord blood is mainly Glu-OC, and Glu-OC is replaced with Gla-OC within 5 d of life after vitamin K supplement. The IRMA assay fails to distinguish Gla-OC from Glu-OC and caution is needed to estimate bone turnover with this method in the perinatal period.