[A nationwide survey on the uses of melatonin and ramelteon in Japanese children].

OBJECTIVE: We carried out a questionnaire survey to investigate the uses of melatonin and ramelteon in Japanese children. METHODS: We sent a questionnaire to councilors of the Japanese Society of Child Neurology by e-mail, and sent the same questionnaire to members of the Japanese Society of Pediatric Psychiatry and Neurology by postal mail. RESULTS: During the first phase of the survey, 220 responses were obtained, and 45% of the respondents prescribed melatonin. Imported supplements and chemical reagents were used by 64% and 29% of melatonin prescribers, respectively. Some prescribed melatonin without patient consent or institutional approval. In patients with pervasive developmental disorder, cerebral palsy, attention-deficit hyperactivity disorder, Rett syndrome, and visual disturbance, melatonin was prescribed by 37%, 29%, 10%, 6%, and 6% of the respondents, respectively. In terms of sleep disorders, melatonin was prescribed by 49% and 42% of respondents in patients with circadian rhythm disorders and insomnia, respectively. Ramelteon was prescribed by 52% of respondents. Regarding types of target diseases and sleep disorders, the use of ramelteon differed little from that of melatonin. In the second phase of the survey on the use of melatonin, 23 doctors prescribed the drug for 254 patients. The daily effective dose ranged from 0.2 mg to 8 mg in patients aged 2 months to 37 years. In more than 60% of the patients who took melatonin, PDD was diagnosed. In the patients with melatonin for insomnia, 90% and 25% had difficulty falling asleep and disorders in circadian rhythm, respectively. CONCLUSIONS: Both melatonin and ramelteon were widely prescribedin Japanese children. Melatonin tended to be used without sufficient ethical consideration in Japan, indicating the necessity of melatonin as medicine. Then, careful determination of an applicable dose are required in future studies.

Development and validation of the Japanese version of the Bedtime Procrastination Scale (BPS-J).

BACKGROUND: The average sleep duration of Japanese people is shorter than that of people from other countries, and bedtime procrastination is suspected to be one of the factors contributing to this issue. This study aimed to develop and validate the Japanese version of the Bedtime Procrastination Scale (BPS-J). METHODS: The BPS-J was developed through procedures including the translation and back-translation of the scale, cognitive interviews with 100 participants who reported having experiences of being diagnosed with insufficient sleep syndrome (ISS) or receiving treatment for ISS using open-ended online questionnaires, and expert checking. To investigate the scale's validity and reliability, an online survey was conducted with daytime workers aged 20 - 65 years without a history of sleep disorders other than ISS. Half the participants were retested using the same survey after 14 days. Participants' responses to the Brief Self-Control Scale (BSCS), General Procrastination Scale (GPS), and Munich ChronoType Questionnaire (MCTQ), and data on sleep-related variables such as sleep duration on workdays and the days per week of fatigue or sleep loss, sex, and age, were collected. RESULTS: We analyzed data from 574 participants to assess scale validity. We then analyzed data from 280 participants to determine test-retest reliability. Confirmatory factor analyses revealed that the two-factor model without Item 2 was most suitable for the BPS-J, unlike other language versions. Regardless of the full-item model or the model with Item 2 eliminated, sufficient reliability and significant correlations with the BSCS, GPS, MCTQ, and sleep-related variables such as sleep duration per night on work days, days per week of feeling fatigued, and days per week of sleep loss were observed. Logistic and linear regressions showed that the relationships between the BPS-J, sleep-related variables, and MCTQ were maintained after adjusting for sex and age. CONCLUSION: The BPS-J had sufficient validity and reliability. Further, eliminating Item 2 from the original version of the BPS strengthened the ability to survey Japanese daytime workers.

Pre-movement gating of somatosensory evoked potentials in Tourette syndrome.

OBJECTIVE: Tourette syndrome (TS) is a neurobehavioral disorder characterized by motor and vocal tics. Simple tics are purposeless involuntary movements that spontaneously resolve during middle adolescence. Complex tics appear to be semi-voluntary movements that may become intractable when associated with obsessive-compulsive disorder (OCD). Sensory tics or urges preceded by tics suggest sensorimotor processing impairment in TS. We aimed to clarify its pathophysiology by exploring the pre-movement gating (attenuation) of somatosensory evoked potentials (SEPs). METHODS: We examined 42 patients (aged 9-48 years), 4 of whom underwent follow-up assessment, along with 19 healthy controls. We defined patients with only simple tics as TS-S and patients with complex tics as TS-C. Pre-movement gating of SEPs was assessed using a previously described method. Frontal N30 (FrN30) amplitudes were compared between pre-movement and resting states. The gating ratio of pre-movement/resting amplitude of the FrN30 component was assessed: the larger the ratio, the less the gating. RESULTS: The gating ratio for TS-C patients was larger than that of TS-S patients and healthy controls, but a statistical difference between TS-S and TS-C appeared after 15 years and over (p < 0.001). There were no significant differences in the gating ratio between TS-S patients and healthy controls. The gating ratio was related to the severity of OCD (p < 0.05). CONCLUSION: Sensorimotor processing was preserved for simple tics but impaired in complex tics, specifically after middle adolescence. Our study supports an age-dependent dysfunction of both motor and non-motor cortico-striato-thalamo-cortical circuits in complex tics. SEP gating seems promising as a tool for assessing age-dependent sensorimotor disintegration in TS.

Corrigendum: Decrease in social zeitgebers is associated with worsened delayed sleep-wake phase disorder: findings during the pandemic in Japan.

[This corrects the article DOI: 10.3389/fpsyt.2022.898600.].

Decrease in Social Zeitgebers Is Associated With Worsened Delayed Sleep-Wake Phase Disorder: Findings During the Pandemic in Japan.

Background: Delay in sleep-wake rhythms was observed in the general population during the coronavirus disease 2019 (COVID-19) pandemic. Patients with delayed sleep-wake phase disorder (DSWPD) may have also experienced exacerbation of symptoms, but no studies have investigated this topic. In this study, we aimed to retrospectively examine the changes in symptoms of outpatients with DSWPD both before and during the pandemic and to identify the factors associated with the exacerbation of sleep-wake rhythms. Methods: We included outpatients with DSWPD aged 16 years or older who visited the outpatient clinic due to sleep disorders between January and September 2020. Decreased social zeitgebers was defined as a reduction of 50% or more in the frequency of commuting to school or work during the COVID-19 pandemic. The severity of DSWPD was assessed using the clinical global impressions - severity of illness (CGI-S) at two points: before and during the pandemic. We defined the worsened, unchanged, and improved groups as those whose CGI-S scores worsened by at least one point, remained unchanged, and improved by at least one point, respectively. Multivariate logistic regression analysis was performed to determine the factors associated with worsened DSWPD symptoms. Results: Sixty patients with DSWPD were eligible for this study. Even before the pandemic, patients who were unemployed or did not attend school tended to show more severe DSWPD symptoms. During the pandemic, 27 patients belonged to the worsened group; 28 patients, unchanged group; and 5 patients, improved group. Decreased social zeitgebers (odds ratio [OR] = 6.668, 95% confidence interval [CI]: 1.653-26.891, p < 0.05) and comorbid mood disorders (OR = 8.876, 95% CI: 1.714-45.974, p < 0.05) showed independent significant associations with the worsening of DSWPD symptoms. Conclusions: During the pandemic, the symptoms of DSWPD tended to worsen. The obtained findings emphasize the importance of social zeitgebers, suggesting the need for external motivation in DSWPD treatment.

Melatonin Treatment and Adequate Sleep Hygiene Interventions in Children with Autism Spectrum Disorder: A Randomized Controlled Trial.

Robust clinical evidence has not been available for melatonin, a drug commonly administered for treating sleep problems of children with autism spectrum disorder (ASD). In a phase 3 randomized, placebo-controlled clinical trial, we administered 1-mg melatonin (n = 65), 4-mg melatonin (n = 65), or placebo (n = 66) to196 children with ASD once daily before bedtime under adequate sleep hygiene interventions. The primary outcome was sleep onset latency (SOL) assessed with the electronic sleep diary. SOL shortened significantly in the 1- and 4-mg melatonin groups compared to the placebo group (- 22.0, - 28.0, and - 5.0 min, respectively; p < 0.0001 each). This therapeutic regimen of melatonin is a reasonable clinical approach to cope with ASD-emergent difficulties in children with ASD.

Sleep disturbance and health-related quality of life in Parkinson's disease: A clear correlation between health-related quality of life and subjective sleep quality.

INTRODUCTION: Comorbid insomnia and poor sleep quality in Parkinson's disease (PD) are associated with a poor health-related quality of life (HRQoL). However, the relationship between HRQoL and sleep measures obtained using polysomnography (PSG) remains unclear. We aimed to examine the association between various sleep measures and HRQoL in PD patients. METHODS: We retrospectively included patients with PD who underwent PSG and responded to self-administered questionnaires including the Pittsburgh Sleep Quality Index (PSQI) and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: The patients' (n = 120) mean age was 67.06 (SD = 8.77) years, and their mean Hoehn and Yahr stage was 2.25 (SD = 0.78). A higher PSQI score (worse subjective sleep quality) was correlated in PSG with shorter sleep latency, less N1 sleep, and more N2 sleep. Multiple regression analysis showed that the total PSQI score correlated with both physical and mental HRQoL (p < 0.001 in both cases). However, neither type of HRQoL studied correlated with objective sleep measures, including indicators of sleep architecture, sleep-disordered breathing, and sleep related movement disorders. CONCLUSION: Despite the association between subjective sleep quality and HRQoL, the associations between objective measures and HRQoL were negligible. Objective sleep fragmentation may not be perceived as a sleep disturbance in patients with PD, and therefore may not adversely affect their subjective health, given the paradoxical correlation between PSQI score and sleep architecture.

Relationship between COVID-19-specific occupational stressors and mental distress in frontline and non-frontline staff.

This study investigated the difference in the severity of mental distress and factors contributing to mental distress in frontline and non-frontline healthcare professionals during the coronavirus disease (COVID-19) pandemic. A cross-sectional web-based survey of medical staff collected by snow-ball sampling was performed in Japan in October 2020 using the Kessler Psychological Distress Scale (K6) as an outcome measure for mental distress. Originally developed items asking about the degree of change in psychological and physical burdens, COVID-19-related fear, and experience of discrimination were obtained. The median score of the K6 was 7 in the frontline staff group (n = 86) and 6 in the non-frontline staff group (n = 504), without a statistically significant difference. Multiple regression analyses showed that among the participants, an increase in psychological burden and COVID-19-related fear was significantly associated with mental distress in both groups. Experience of discrimination was significantly associated with mental distress only in the frontline staff group. However, an increase in physical burden was significantly associated with mental distress only in the non-frontline staff group. The results indicate that the factors contributing to mental distress between frontline and non-frontline staff can be different, although the severity of mental distress is comparable between them.

Temperament and Sleep-Wake Behaviors from Infancy to Toddlerhood.

Sleep-wake behaviors and temperament were examined longitudinally for trait stability and relationship to behavioral state regulation from infancy to early childhood. Subjects were 120 low-risk, full-term infants from a middle class sample. At 6 weeks, parents completed 3 consecutive days of the Baby's Day Diary which measures sleep, wake, fuss, feed and cry states and the Infant Characteristics Questionnaire. At 16 months, parents assessed sleep behaviors with the Sleep Habits Inventory and temperament with the Toddler Symptom Checklist. At 24 months, parents repeated 3 days of the Baby's Day Diary. Structural Equation Modeling was used to examine cross-age hypotheses for sleep-wake and temperament associations. From early infancy to toddlerhood, sleep-wake behaviors and irritable temperament were notably stable but independent in this cohort.

Psychological burden of attention-deficit/hyperactivity disorder traits on medical workers under the COVID-19 outbreak: a cross-sectional web-based questionnaire survey.

OBJECTIVES: There are numerous reports on the psychological burden of medical workers after the COVID-19 outbreak; however, no study has examined the influence of developmental characteristics on the mental health of medical workers. The objective of this study was to examine whether the developmental characteristics of medical workers are associated with anxiety and depression after the COVID-19 outbreak. DESIGN: We conducted an online cross-sectional questionnaire survey in October 2020. PARTICIPANTS AND SETTING: The data of 640 medical workers were analysed. The questionnaire included items on sociodemographic data, changes in their life after the COVID-19 outbreak and symptoms of depression, anxiety, attention-deficit/hyperactivity disorder (ADHD) traits and autism spectrum disorder traits. MAIN OUTCOMES: Depression symptoms were assessed by the Patient Health Questionnaire-9 and anxiety symptoms were assessed by the Generalised Anxiety Disorder-7. A series of hierarchical multiple regression analyses were performed to test the effects of developmental characteristics on depression and anxiety symptoms after controlling for sociodemographic factors and changes in participants' lives after the COVID-19 outbreak. RESULTS: Increases in physical and psychological burden were observed in 49.1% and 78.3% of the subjects, respectively. The results of a multiple regression analysis showed that ADHD traits were significantly associated with both depression (ß=0.390, p<0.001) and anxiety (ß=0.426, p<0.001). Autistic traits were significantly associated with depression (ß=0.069, p<0.05) but not anxiety. Increased physical and psychological burden, being female, medical workers other than physicians and nurses, fear of COVID-19 and experience of discrimination were also significantly associated with both depression and anxiety. CONCLUSION: Globally, the burden on medical workers increased. This study suggested that medical workers with higher ADHD traits may need special attention during the COVID-19 pandemic.

Sleep fragmentation and evidence for sleep debt in alcohol-exposed infants.

BACKGROUND: Infants exposed prenatally to alcohol are at increased risk for poor neurodevelopmental outcome including Sudden Infant Death Syndrome. AIM: To examine the relationship between prenatal alcohol exposure, sleep, arousal and sleep-related spontaneous motor movements in early infancy. STUDY DESIGN: Low-income women (N=13) were interviewed regarding pre- and pregnancy rates of alcohol, cigarette smoking and other substance use in the perinatal period. Infants were examined in a laboratory nap study using EEG, videography and actigraphy at 6-8 weeks of age. Estimates of maternal pre- and pregnancy alcohol use were used to divide infants into high vs. low maternal alcohol use groups. SUBJECTS: Mother-infant dyads recruited from a family practice clinic. OUTCOME MEASURES: Sleep-related spontaneous movements, behavioral state, and maternal assessments of infant alertness and irritability. RESULTS: Pre-pregnancy rates of alcohol consumption including binge drinking correlated with maternal report of poor infant alertness, and increased irritability. High maternal exposure groups showed increased sleep fragmentation, e.g., frequency and duration of wakefulness following sleep onset and decreased active sleep. Bout analysis of the temporal structure of sleep-related spontaneous movements showed significantly reduced bout duration associated with high maternal alcohol use. CONCLUSION: These results present evidence that prenatal alcohol exposure disrupts postnatal sleep organization and suppresses spontaneous movements during sleep, and increased sleep fragmentation promotes sleep deprivation. Results are consistent with the SIDS model of chronic sleep debt and suggest that attenuated sleep-related movements should be examined as an important modulator of cardiorespiratory functions during sleep in high-risk groups.

Basal ganglia lesions in a patient with 3-hydroxyisobutyric aciduria.

3-hydroxyisobutyric aciduria (3HiB-uria) is a very rare organic aciduria that involves valine metabolism. We report the case of a 7-year-old boy with 3HiB-uria who has suffered more than 20 ketoacidotic episodes since the age of 15 months. In the most recent ketoacidotic episode, which was particularly severe, he developed mild dystonia and choreoathetosis. Magnetic resonance imaging (MRI) revealed bilateral swelling and signal abnormalities of the putamina and heads of the caudate nuclei. The abnormal movements showed a gradual improvement over several months, in correlation with neuroradiological findings. 3HiB-uria should be recognized as one of the group of branched chain organic acidemias that can produce lesions in the basal ganglia.

Fluctuating hearing loss, episodic headache, and stroke with platelet hyperaggregability: coexistence of auditory neuropathy and cochlear hearing loss.

We encountered a 10-year-old girl with fluctuating sensorineural hearing loss, episodic headache, and white matter stroke. Strenuous exercise, febrile illness, and general anesthesia all temporarily worsened hearing. Audiologic findings were asymmetric: left-sided retrocochlear dysfunction consistent with auditory neuropathy contrasted with cochlear hearing loss in the right ear. Platelets obtained during a headache-free period showed excessive responsiveness to collagen in vitro, while episodic elevations of thromboxane B(2) and thrombin-antithrombin III complex were noted in blood sampled during headache. Treatment of hyperaggregability of platelets with aspirin and antioxidant vitamins relieved headache, while adenosine triphosphate administration improved hearing thresholds. In this patient, hearing impairment and white matter strokes appeared to respectively related to impaired blood flow to the cochlea and white matter caused by platelet dysfunction triggered by physiologic stresses.

[Continuous midazolam infusion for refractory nonconvulsive status epilepticus in children].

We examined efficacy of continuous midazolam (MDL) infusion in seven episodes of refractory nonconvulsive status epilepticus (NCSE) in five children. Diagnosis included Lennox-Gastaut syndrome (two cases), and symptomatic generalized epilepsy, ring chromosome 20 syndrome, and epilepsy with continuous spike-waves during slow-wave sleep (one case each). One patient with Lennox-Gastaut syndrome and another with ring chromosome 20 syndrome had two episodes of NCSE. MDL was given as an initial bolus of 0.15 to 0.3 mg/kg, followed by continuous intravenous infusion at 0.1 to 0.2 mg/kg/hr. The infusion rate was increased slowly by 0.1 mg/kg/hr every 0.5 to 1.0 hr, up to 0.4 mg/kg/hr or until NCSE was controlled. The electroencephalogram, vital signs, blood pressure, and oxygen saturation were monitored during therapy. Electrical status epilepticus was abolished within a few hours in five of the seven episodes, and two patients could maintain wakefulness, oral intake, and bowel and bladder control throughout the continuous infusion. In one patient in whom NCSE recurred, it then remained uncontrolled even at a maximum dose. Serious complications such as respiratory depression or hypotension were not observed. Continuous intravenous infusion of MDL was effective and safe for NCSE in children, and can be used as firstline therapy for this condition.

Central respiratory pauses, sighs, and gross body movements during sleep in children.

Sighs (SIs) and gross body movements (GMs) during sleep are common spontaneous, arousal behaviors during sleep. These physiological behaviors either precede or follow central respiratory pauses (CPs) during sleep in normal subjects. However, little attention has been paid to the temporal relationships between CPs and spontaneous behaviors except in early infancy. In the present study, the age- and state-related changes in the frequency and duration of apnea-behavior relationships were studied cross-sectionally in 19 healthy children aged between 3 months and 7 years of age. CPs, SIs, and GMs were assessed in a single all-night polysomnography and respiratory inductive plethysmography. We divided the data into two age groups: less and more than 15 months of age. The results showed that frequency of CPs > or = 10 s increased with age, while the frequency of GMs and SIs decreased. Isolated CPs appeared more frequently during rapid-eye-movement sleep (REMS) than during nonrapid-eye-movement sleep (NREMS). The frequency of both SIs and GMs that appeared after CPs was higher during REMS than during NREMS. The sum of CPs preceded by SI, and CPs preceded by GM accounted for about 75% of all central apnea events. These two events appeared more frequently during NREMS than during REMS and the duration of both events in NREMS increased significantly with age. During NREMS, few and delayed behaviors thought to restart respiration after CPs have been described. Future work should examine developmental differences in the occurrence of physiological behaviors in relation to CP in NREMS and REMS.

Congenital monomelic neurogenic disorder with calf muscle hypertrophy.

An 8-year-old girl had hypertrophy of the right calf muscle since birth, with progressive ankle contracture and mild muscle weakness. Her right leg was 3 cm shorter than her left. Electromyography and biopsy of the affected muscle showed neurogenic changes. She also had neurogenic bladder and spina bifida occulta at the S1 level. We believe that the spina bifida was responsible for the neurogenic changes in her right calf, but could not find definite evidence for this association. Although cases with neurogenic muscle hypertrophy, especially calf muscle hypertrophy, have been reported, none of them was congenital or associated with spina bifida occulta.

[Neuropsychological and neuroradiological evaluation of a child with frontal and temporal lobe dysfunction following acute encephalopathy].

A 12-year-old boy showed abnormalities of higher brain functions following acute encephalopathy, in spite of almost normal intelligence. Neuropsychological tests and ordinary intelligence tests could clearly demonstrated his visual and auditory memory impairment and frontal lobe dysfunction. Brain magnetic resonance imaging showed lesions of the bilateral-temporal lobes, and single photon emission tomography showed reduced cerebral blood flow in the temporal and frontal areas bilaterally. The distribution of the lesions was compatible with his clinical symptoms and with the results of the neuropsychological tests. The combination of neuropsychological and neuroradiological examinations is helpful for evaluating higher brain functions precisely. We should make better use of these examinations in determining the most appropriate treatment for patients, particularly children with higher brain dysfunction.

[Serial median nerve SEPs and SSEPs in patients with West syndrome].

We studied serial median nerve somatosensory evoked potentials (SEPs) and short latency somatosensory evoked potentials (SSEPs) in 17 patients with West syndrome. Four of the 7 patients with absent SEPs in the initial examination showed recognizable SEPs in the follow-up studies, associated with improvement of electroencephalogram (EEG). This indicated that SEPs were variable with condition of epilepsy and lack of initial SEPs was not always a poor prognostic factor for seizure control and developmental outcome. Persistent lack of SEPs, however, indicated poor outcome of seizures, EEG and development. Central conduction time in SSEPs did not correlate with seizure or developmental outcome.

[The parents' assessment and needs for home mechanical ventilation in patients with pediatric neurological disorders].

Parents' of patients with pediatric neurological disorders were sent a questionnaire, on their assessment and needs for home mechanical ventilation (HMV). Nine of 12 enrolled families responded. Respirator troubles were handled by a contracted HMV company. Decreased SpO2 levels and endotracheal bleeding were cared by family members under telephone instructions of doctors, though they felt anxious about dealing the problems. The mothers felt happy to live with their children by virtue of HMV, however, they had strong stress about the management of emergency care and medical care technique. They also felt very tired physically, but refreshed by being free from daily HMV care for a short time and enjoying their own time. The parents were not satisfied with the present house facilities and education system. They evaluated the induction of HMV positively but were most anxious for a better home care nursing system, doctors responding to a house call, more information on HMV, reduction of their anxieties and fatigue, and improvement of economical and educational environments.

[Three cases with severe motor and intellectual disabilities presenting the severest condition caused by prolonged non-convulsive status epilepticus].

Three patients with severe motor and intellectual disabilities presented deterioration of the activities of daily living, which was revealed to be caused by prolonged non-convulsive status epilepticus (NCSE). Their condition improved by the treatment with antiepileptics. Case 1, a 4-year-old girl with profound psychomotor retardation and past history of West syndrome of unknown etiology, became unable to sit and eat orally above age of two years. EEG showed continuous generalized slow spike and wave bursts indicating NCSE. Continuous intravenous infusion of midazolam abolished EEG abnormalities of NCSE, and she regained the ability of oral feeding. Case 2, a 3-year-old boy with Angelman syndrome and past history of West syndrome, presented decreased mental response, poor oral intake and somnolence. EEG showed continuous slow spike and wave bursts, indicating NCSE. High-dose phenobarbital therapy and continuous intravenous injection of vitamin B6 were effective, and remarkably improved his psychomotor activities. Case 3, a 3-year-old boy with Lennox-Gastaut syndrome, developed decreased psychomotor activity and loss of vocalization and walking. He could not sit by himself and became nearly bed-ridden. EEG showed very frequent generalized spike and wave bursts, showing NCSE. Continuous infusion of thiopental diminished NCSE, and he could walk again. Psychomotor deterioration in patients with severe motor and intellectual disabilities may be caused by NCSE, which should not be overlooked.