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Summary: Sleep disturbances in children with epilepsy are prevalent, and are associated with substantial adverse medical and psychosocial consequences. This study is a 5‐year follow‐up of a clinic‐based sleep intervention study that randomized 100 toddlers and preschool‐age children with epilepsy to a usual care group or a sleep intervention group. The intervention group received standard paediatric neurology care plus three education sessions during the child's routine clinic visit. The outcomes measured were: (1) child sleep by actigraphy and parental report; and (2) maternal sleep and depression. We aimed to evaluate the long‐term benefits of a clinic‐based sleep intervention for paediatric epilepsy. In total, 42 families (42.0%) participated. The average child's age at follow‐up was 9.55 years. Thirty‐eight (90.5%) children were not obtaining sufficient sleep at baseline, and 40 (95.2%) at the 5‐year follow‐up. The numbers of children with clinically significant sleep disturbances were 40 (95.2%) at baseline and 36 (85.7%) at the 5‐year follow‐up. Fourteen mothers (33.3%) had poor sleep quality and high depressive symptoms at both assessment time points. There were no differences (P > 0.05) in the child and maternal outcomes between the two trial arms. Overall, there was no evidence that a clinic‐based sleep intervention that effectively improved multiple aspects of sleep in toddlers and preschool‐age children with epilepsy had long‐lasting beneficial effects. Our findings suggest that sleep interventions for families of children with epilepsy require ongoing reinforcement and monitoring during routine paediatric neurology care to prevent sleep problems from persisting or recurring. [ABSTRACT FROM AUTHOR]

The objective of this study is to assess the prevalence and risk factors for attention-deficit hyperactivity disorder (ADHD) in a large cohort of patients with congenital heart disease (CHD). Patients (n = 695) with CHD who were aged 6–15 years and visited the outpatient clinics in our hospital from June 2015 to May 2017 were enrolled. Their medical records were collected, and the Chinese version of the Swanson, Nolan, and Pelham rating scale (SNAP-IVc) and a questionnaire about neuropsychiatric care-seeking behavior were completed by parents and counselors. Of the 695 patients, the overall prevalence of ADHD was 12.4%, including 3.2% for the combined subtype, 6.8% for the inattentive-predominant subtype, and 2.4% for the hyperactivity/impulsive-predominant subtype. Only the inattention-predominant subtype was significantly more prevalent than in the general population. The prevalence of the inattention-predominant subtype was highest in the patients with cyanotic CHD, high severity index, and in those who had received surgery or cardiopulmonary bypass. Multivariate regression analysis indicated that the risk factors for inattention-related symptoms included postoperative seizure and previous cardiopulmonary bypass (odds ratio: 3.22 and 3.82; P = 0.027 and < 0.001, respectively). Only 58.7% of the patients with probable ADHD ever sought neuropsychiatric care, and only 27% regularly attended neuropsychiatric clinics. The inattention-predominant subtype of ADHD was more prevalent in our CHD patients, especially in those with cyanotic CHD, higher disease severity index, and in those who had undergone a surgical intervention. The percentage of patients receiving regular neuropsychiatric clinic follow-up was low. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study is to examine the safety and efficacy of eltrombopag as first‐line treatment for thrombocytopenia among paediatric patients after haematopoietic stem cell transplantation (HSCT). Methods: Forty‐three childhood patients with thrombocytopenia after HSCT who received eltrombopag were retrospectively analysed. Result: Eltrombopag was began at the median of 27 days after HSCT and lasted for 24 days. Thirty‐five children responded to eltrombopag therapy, and the cumulative platelet recovery rate was 88.9%. The cumulative incidence of platelet recovery was lower (83.9 vs 100%; P =.035) in patients with decreased numbers of megakaryocytes before starting eltrombopag than in those with normal. Factors associated with a significantly elevated response to eltrobopag from univariate analysis were donor type. Results from the multiple regression analysis found that weight (hazard ratio [HR] = 0.7, 95% confidence interval [CI] 0.5–0.9, P =.022), platelet engraftment time (HR = 1.0, 95%CI 1.0–1.0, P =.012) and bone marrow megakaryocytes (HR = 8.0, 95%CI 1.5–43.3, P =.016) before starting eltrombopag were the independent risk factors. Based on Youden's index algorithm in the receiver‐operating characteristic curve, the optimal cut‐off value of the maintenance dose of eltrombopag in predicting nonresponders was 4 mg/kg. The area under the receiver‐operating characteristic curve was 0.923 with sensitivity of 97.8%, specificity of 87.9%, positive predictive value of 72.3%, and negative predictive value of 92%. None of the paediatric patients stopped using eltrombopag due to side effect or intolerability. Conclusion: Eltrombopag is effective and safe in paediatric patients with thrombocytopenia after HSCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may serve as a predictor of the response to eltrombopag. We recommend that the maintenance dose of eltrombopag should not exceed 4 mg/kg/d. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association between daily screen time exposure and both sleep patterns (sleep onset, sleep offset, and nighttime, and daily sleep durations) and sleep disturbances among a clinical sample of children with epilepsy. Design: A cross‐sectional actigraphic sleep study. Methods: A convenience sample of 141 children with epilepsy (1.5–6 years of age) was recruited from an outpatient pediatric neurology clinic of a university‐affiliated children's hospital in northern Taiwan. Participating families completed questionnaires and reported children's screen time use, with children wearing an actigraphy monitor for 7 days to assess sleep patterns. Multivariable linear regression analyses were conducted to examine the association of screen time exposure with the child's sleep patterns and sleep disturbance scores. Findings: Mean minutes per day of screen time exposure was 89.79 ± 83.94 min, with 62 parents (44.0%) reporting their child having >1 hr of screen time daily. Mean daily sleep duration was 9.26 ± 1.01 hr, with 106 children (93.0%) sleeping <10 hr in a 24‐hr period. In multivariate regression models, daily screen time exposure of >1 hour was associated with 23.4‐min later sleep onset (b = 0.39, p =.02), 20.4‐min later sleep offset (b = 0.34, p =.04), and more severe sleep disturbances (b = 2.42, p =.04). Conclusions: In toddlers and preschool‐age children with epilepsy, daily screen time exposure is greater and sleep duration is shorter than the recommended amount, with increased screen time exposure associated with disturbed sleep. Clinical Relevance: Parents need to be informed about the possible adverse impact of screen time exposure on children's sleep and health as well as the importance of limiting screen time exposure to <1 hr per day for their toddlers and preschool‐age children with epilepsy. [ABSTRACT FROM AUTHOR]

We conducted a cross‐sectional study to examine sleep in mothers of children with epilepsy and its relation to their children's sleep. A total of 133 dyads of mothers and children with epilepsy aged 1.5–6 years were recruited between 2015 and 2018 from a children's hospital in northern Taiwan. Participating families provided demographic and health information, with children wearing an actigraphy monitor for 7 days and mothers completing sleep and depressive mood questionnaires. We found that 76 (57.1%) of the mothers had poor sleep quality, with 65 (48.9%) mothers having a clinically significant depressive symptom score. Mean actigraphic wake after sleep onset in children was 1.42 (standard deviation = 0.51) hours, with 126 (94.7%) of the children having a clinically significant sleep disturbance score. Multivariate regression analyses showed that higher depressive symptom scores in mothers (β = 0.14; p <.01) and higher sleep disturbance scores in children (β = 0.07; p =.04) were associated with poorer maternal sleep quality, even when maternal demographic characteristics and the child's clinical and epilepsy variables were considered. Findings from our study suggest that sleep disturbances are a shared problem for mothers and their children with epilepsy. Sleep in both mothers and their children with epilepsy should be evaluated in pediatric neurologic practices, with maternal depressive symptoms screened concurrently. Future pediatric epilepsy studies are warranted to examine whether a family‐based intervention program would be effective to improve sleep in mother‐child dyads and to promote better health and functioning of the entire family. [ABSTRACT FROM AUTHOR]

Introduction: TET2, a member of the Ten‐Eleven translocation gene family, catalyzes the conversion of 5‐methylcytosine to 5‐hydroxymethylcytosine in DNA. Low expression of TET2 has been reported as a prognostic factor for several types of malignancies in adult patients. However, there have been few data on the effect of TET2 mRNA level on the prognosis of children with ALL so far. Methods: In this study, TET2 expression of samples cryopreserved in the liquid nitrogen from January 1, 2007 through December 31, 2011 was retrospectively analyzed in 136 newly diagnosed ALL patients by real‐time polymerase chain reaction (PCR) assay. The patients' samples were divided into two groups by the median value of patients group and divided into TET2 low and TET2 high groups. Results: A total of 136 childhood ALL patients demonstrated lower TET2 expression than control group (P = .038). TET2 mRNA expression levels were correlated with the disease status. In addition, patients with low TET2 expression had lower platelet counts and lower CR rates. Survival analysis showed that low TET2 expression in children with ALL was associated with lower 5‐year overall survival (OS) (63% vs 88%, P = .011) and event‐free survival (EFS) (60% vs 85%, P = .003). Multivariate analysis revealed that low TET2 expression was an independent poor prognostic factor of OS and EFS. Conclusion: Low expression of TET2 in children with ALL is associated with poor prognosis and can be used as a molecular prognostic marker for risk group stratification. [ABSTRACT FROM AUTHOR]

Abstract We designed a cross-sectional study to examine the association between sleep and behavior problems in toddlers and preschool-age children with epilepsy. We found that 71 (78.9%) children slept less than 10 hours in a 24-hour period according to the actigraphy, with 75 (83.3%) children waking for more than an hour during nocturnal sleep. Twenty-five (27.8%) children usually or sometimes had an inconsistent bedtime, and 24 (26.7%) did not sleep the same amount each day. Twenty-nine (32.2%) and 18 (20.0%) children had an internalizing and externalizing problem in clinical range, respectively. Sleep anxiety was significantly (p <.01) associated with increased internalizing and externalizing problems, even after the relevant epilepsy variables were controlled for. Findings from our study suggest that screening of sleep and behavior problems should be part of routine epilepsy care to identify children with problematic sleep and unrecognized sleep disorders and those at risk of behavioral dysfunction. [ABSTRACT FROM AUTHOR]

Background Both refractory convulsive status epilepticus (SE) and super-refractory SE are medical emergencies. However, there are limited data on super-refractory SE in children. Thus, this study focuses on characterizing the demographics, outcomes, and prognostic factors for super-refractory SE in children. Methods This study was a retrospective analysis of super-refractory SE treated in a tertiary referral center in Taiwan. The functional outcome was evaluated by modified Rankin scale (mRS). Significant functional decline was defined as an mRS difference (before hospital admission and at discharge) of more than 2. The variates and the follow-up mRS values were then analyzed statistically. Results We enrolled 134 patients with 191 episodes of convulsive SE and identified 30 patients with 38 episodes of convulsive super-refractory SE. The incidence of convulsive super-refractory SE in the group with SE was 19.9%, and the age ranged from 2.5 months to 17 years. In-hospital mortality was 13.3%, which was much lower than that of adult cohorts. Newly acquired epilepsy and cognitive deficit occurred in 100% and 88.5%, respectively. Newly acquired epilepsy, as a sequel of super-refractory SE, was observed in all 18 patients (100%) who survived and had no history of epilepsy. Significant functional decline (mRS difference of more than 2) at discharge occurred in 76.7%. Poor functional outcome was associated with acute symptomatic etiology (P < 0.001) and the number of anesthetic agents (P = 0.002). The functional outcome improved after 1 year of follow-up in our population. Conclusions Super-refractory SE is associated with significant morbidity and mortality in children. However, the in-hospital mortality rate is much lower compared with adults. The functional outcome in children is associated with acute symptomatic etiology and the number of anesthetic agents and may improve after long-term follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To describe sleep patterns in young children with epilepsy and to examine levels of agreement between measurements derived from actigraphy and diary recordings. Design: Cross‐sectional study. Methods: Eighty‐nine toddlers and preschool‐aged children with epilepsy wore an actigraph on their wrists for 7 consecutive days. Parents and caregivers maintained a concurrent sleep diary while the child was wearing the monitor. Levels of agreement between actigraphy and diary recordings were examined using the Bland and Altman method separately for all recording days, weekdays, and weekends. Findings: Discrepancies between actigraphy‐derived and diary‐documented sleep onset, sleep offset, actual sleep at night, wake after sleep onset, and daytime sleep were ±35, ±15, ±82, ±70, and ±29 min, respectively. Differences between actigraphy and diary‐derived sleep variables were consistently greater for weekends than for weekdays. Discrepancies between actigraphy and diary‐derived actual sleep at night were significantly greater for children who slept alone than for those who co‐slept with a parent. Conclusions: Our study demonstrates an acceptable agreement between actigraphy and diary recordings for sleep onset, sleep offset, and daytime sleep, but insufficient agreement for actual sleep at night and wake after sleep onset, with parents of children sleeping alone more likely to misestimate child sleep behaviors. Deviation of weekend sleep from weekdays further decreased the accuracy of parental sleep estimates and increased the discrepancies between actigraphy and diary. Clinical Relevance: Sleep in children with epilepsy assessed using diary recordings alone could be misleading, and actigraphy should be preferred over diaries when resources are available. [ABSTRACT FROM AUTHOR]

Aromatic L-amino acid decarboxylase (AADC) deficiency is an uncommon inherited neurometabolic disease. The clinical presentations and MR findings in children with AADC deficiency were investigated. Total 12 children (6 boys, 6 girls), aged from 9 to 50 months (mean, 23 ±13 months), with AADC deficiency, were enrolled for analysis. Of 12 patients enrolled, clinical presentations included global developmental delay with generalized hypotonia in 12 (100%), dystonia in 12 (100%), oculogyric crisis in 12 (100%), and excessive sweating in 8 (67%). Sleep problem was also found in 4 (33%). Of 15 MR examinations, the major changes included 6 (40%) with diffusely prominent bilateral frontal sulci, 10 (67%) with prominent frontal horns, and 12 (80%) with hypomyelination. In AADC patients, the frontal horn was significantly widened ( P < 0.01), and the volume of caudate nucleus was also significantly smaller than that of controls ( P = 0.02). The ratios of thickness of the splenium to that of the genu of corpus callosum were also significantly increased ( P < 0.01). There was also significant decrease of fiber density indices in major white matter fiber tracts. Using Tract-Based Spatial Statistics approach, we also revealed significant change in major fiber tracts related to language function and motor function. In conclusion, the present study indicated that AADC deficiency may have significant impact on brain development, especially the frontal lobe and fiber tracts related to language function and motor function. Long-term follow-up of brain MRI in patients with AADC deficiency may clarify the possible effect of AADC deficiency on brain development. Hum Brain Mapp 38:1532-1540, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Both epilepsy and tic disorders may share common mechanisms with the involvement of abnormal cortical-basal ganglion circuit connection and dopaminergic dysfunction. However, the association between epilepsy and tic disorders has never been studied. This study investigated the risks of developing tic disorders among children with epilepsy using databases of a universal health insurance system in Taiwan. The data analyzed in this study were retrieved from the National Health Insurance Research Database in Taiwan. The study cohort included children with epilepsy between 2001 and 2007 (n=2629) and a three-fold age- and gender-matched controls (n=7887). All subjects were followed up for 3 years from the date of cohort entry to identify their admissions due to tic disorders (ICD-9-CM codes 307.2, 307.20-307.23). Cox hazard regression analysis was performed to estimate the effect of epilepsy on the occurrence of tics. The epilepsy cohort had a higher prevalence of tics (1.7% vs. 0.2%), and a 8.70-fold increased risk of developing a tic disorder compared with the controls (adjusted hazard ratio (AHR) 8.70, 95% confidence interval (CI) 4.26-16.37, p<0.001). Male patients were observed to have a higher risk of developing a tic disorder (AHR 1.90, 95% CI=1.04-3.46, p<0.001) compared to female individuals. Patients with multiple antiepileptic drugs treatment also exhibited higher crude OR for developing tic disorders. This nationwide population-based cohort study, for the first time, demonstrated that there is a significantly increased risk for tic disorders among children with epilepsy. We also found males, attention deficit disorder and the use of multiple AEDs to be independent risk factors of tic disorders. Closely evaluating possible tic disorders would be crucial for improving the outcome and life quality in children with epilepsy. [ABSTRACT FROM AUTHOR]

Background/Purpose: The OSA-18 questionnaire is one of the most widely-used sleep quality measurements in children. We tested the applicability and cross-cultural validation of the traditional Chinese version OSA-18 questionnaire. Methods: This cross-sectional study was conducted in a tertiary medical referral center. The translation and cultural adaptation of the OSA-18 questionnaire were performed based on Brislin's revised model. A total of 109 children aged 2–18 years old with sleep problems were recruited. Overnight polysomnography and the OSA-18 questionnaire were administered. The reliability and validity of the traditional Chinese version of OSA-18 questionnaire were verified. Results: Excellent test–retest reliability and good internal consistency were achieved, and the validity of OSA-18 with overnight polysomnography was confirmed. The domain of sleep disturbance, daytime function, caregiver concerns, and the OSA-18 total scores were significantly higher in sleep apnea patients. The domain of caregiver concern had the highest score, while those of emotional distress had the lowest scores. The optimal cut-off point of the OSA-18 total scores for detecting obstructive sleep apnea was 67. Conclusion: The traditional Chinese version of OSA-18 demonstrated high reliability and good validity in our study. The domain of caregiver concern is the major element in Taiwanese children with sleep-disordered breathing. [ABSTRACT FROM AUTHOR]

Background: Cyclic vomiting syndrome (CVS) is an episodic nausea and non-bilious vomiting disorder characterized by recurrent stereotypic symptoms with disease-free intervals. CVS in children is associated with a high prevalence of migraine, and is commonly considered a precursor to migraine. This study aimed to investigate the clinical manifestations of pediatric CVS and its prognosis, and to clarify its relationship with the risk of migraine development in children.Methods: The clinical features of children diagnosed with CVS before the age of 18 years at the designated hospital were retrospectively studied over the past 30 years (1976-2006) based on the Rome III or ICHD II criteria. Clinical evaluations, including age of onset, sex, family history, symptoms and duration during attacks, frequency, trigger events, electroencephalogram, treatment and subsequent development of migraine were assessed from chart records and telephone interviews.Results: Thirty-five children (17 males and 18 females) were enrolled. Their age of onset ranged from 2 to 17 years (mean, 6.8 ± 3.1 years) and frequency of attacks ranged from once to 36 times per year (mean, 8.2 ± 7.6 times). Duration of symptoms during each attack ranged from 1 to 45 days (mean, 5.9 ± 7.3 days). Of 20 children assessed for migraine development, seven subsequently developed typical migraine symptoms. There was younger onset age in the migraine-positive subgroup (5 ± 1.7 years) than in the migraine-negative subgroup (8.9 ± 3 years; p = 0.001). Co-morbid headache during CVS attack was also more evident in the migraine-positive subgroup (28.6%vs. 0%).Conclusion: Results of the study show that younger onset age and headache during CVS attacks may have increased risk of migraine development. Large-scale prospective studies are warranted to further clarify the relationship between CVS and migraine. [ABSTRACT FROM AUTHOR]

The association between epilepsy and Tourette syndrome has rarely been investigated. In this retrospective cohort study, we analyzed a dataset of 1,000,000 randomly sampled individuals from the Taiwan National Health Insurance Research Database to determine the risk of epilepsy in children with Tourette syndrome. The study cohort consisted of 1062 patients with Tourette syndrome aged ≤ 18 years, and the control group consisted of three times the number of age- and sex-matched patients without Tourette syndrome, who were insurants, from the same database during the same period. The Tourette syndrome group had an 18.38-fold increased risk of epilepsy than the control group [hazard ratio=18.38, 95% confidence interval (CI)=8.26-40.92; P<0.001]. Even after adjusting for the comorbidities, the risk of epilepsy in the Tourette syndrome group with comorbidities remained high (hazard ratio=16.27, 95% CI=6.26-18.46; P<0.001), indicating that the increased risk was not associated with comorbidities. This population-based retrospective cohort study provides the first and strong evidence that Tourette syndrome is associated with a higher risk of epilepsy. A close follow-up of children with Tourette syndrome for the development of epilepsy is warranted. [ABSTRACT FROM AUTHOR]