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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., (© 2023 European Sleep Research Society.)

Management of pediatric epilepsies poses unique challenges around diagnosis, treatment options, comorbidities, and the potential for these factors to interact with processes in the developing brain. In pediatric patients, broad-spectrum antiseizure medications (ASMs) with minimal potential for adverse events (AEs) and limited impact on cognition and behavior are preferred. Perampanel is a first-in-class ASM with broad-spectrum efficacy, a tolerable safety profile, minimal negative impact on cognitive function, and other features that make it a viable treatment option in this patient population. However, evidence and experience of its use in pediatric patients are less extensive than in adult patients. Experts in pediatric epilepsy across the region convened at a series of meetings to discuss the use of perampanel in pediatric patients, including dose optimization, AE prevention and management, and considerations in particular groups. This article summarizes key evidence for perampanel in the pediatric population and consolidates the experts' recommendations for using the ASM in managing pediatric epilepsies., Competing Interests: Declaration of competing interest Derrick Wei Shih Chan has participated in data safety monitoring and/or advisory boards for Singapore Health Services and Eisai and is President of the Singapore Epilepsy Society and the Singapore Epilepsy Foundation. Surachai Likasitwattanakul has received speaker's honoraria from GSK, Sanofi, Janssen, and Eisai. Akihisa Okumura has received speaker's honorarium from Eisai. Benilda Sanchez-Gan has received speaker's honoraria from Abbott, GlaxoSmithKline Philippines, HI-Eisai Pharmaceutical, Pediatrica, Sandoz Philippines, Sun Pharma Philippines, and Torrent Pharma Philippines and is a member of the Board of Trustees of the Child Neurology Society Philippines. Sheffali Gulati, Wang-Tso Lee, Byung Chan Lim, Kam Tim Liu, and Yi Wang declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Coenzyme Q10 (CoQ10) is one of the essential substances for mitochondrial energy synthesis and extra-mitochondrial vital function. Primary CoQ10 deficiency is a rare disease resulting from interruption of CoQ10 biosynthetic pathway and biallelic COQ4 variants are one of the genetic etiologies recognized in this hereditary disorder. The clinical heterogenicity is broad with wide onset age from prenatal period to adulthood. The typical manifestations include early pharmacoresistant seizure, severe cognition and/or developmental delay, dystonia, ataxia, and spasticity. Patients may also have multisystemic involvements such as cardiomyopathy, lactic acidosis or gastro-esophageal regurgitation disease. Oral CoQ10 supplement is the major therapeutic medication currently. Among those patients, c.370G > A variant is the most common pathogenic variant detected, especially in Asian population. This phenomenon also suggests that this specific allele may be the founder variants in Asia. In this article, we report two siblings with infantile onset seizures, developmental delay, cardiomyopathy, and diffuse brain atrophy. Genetic analysis of both two cases revealed homozygous COQ4 c.370G > A (p.Gly124Ser) variants. We also review the clinical manifestations of primary CoQ10 deficiency patients and possible treatment categories, which are still under survey. As oral CoQ10 supplement may improve or stabilize disease severity, early precise diagnosis of primary CoQ10 deficiency and early treatment are the most important issues. This review article helps to further understand clinical spectrum and treatment categories of primary CoQ10 deficiency with COQ4 variant., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Adequate control of pharmacoresistant epilepsy continues to be a challenge. Multiple studies have reported the benefits of epilepsy surgery and vagus nerve stimulation for children with pharmacoresistant epilepsy. Little is known about the role of vagus nerve stimulation for children with failed epilepsy surgeries. The aim of this study was to examine the effects of vagus nerve stimulation on seizure frequency reduction for children with failed epilepsy surgeries. We retrospectively reviewed 85 children with pharmacoresistant epilepsy who underwent vagus nerve stimulation. Six of these patients underwent epilepsy surgery before vagus nerve stimulation (group I) and 79 patients received only vagus nerve stimulation (group II). We recorded seizure frequency at 3, 12, 24 and 36 months after vagus nerve stimulator implantation. Both groups had reduced seizure frequencies at the 3-, 12-, 24- and 36-month follow-up (p = 0.044 for group I trends and 0.008 for group II trends). Vagus nerve stimulator implantations significantly improve seizure frequency for children with or without previous epilepsy surgery at 3, 12, 24 and 36 months. These findings suggest that vagus nerve stimulation should be considered an alternative therapy for pediatric patients with previous failed surgeries., (© 2020. Belgian Neurological Society.)

Background: Epilepsy is one of the most common chronic neurological diseases in children. Sleep disorders tend to increase the risk of seizures, and research has found that moderate physical activity may improve the quantity and quality of sleep in adults. However, the link between physical activity level and sleep patterns in toddlers and preschool-age children with epilepsy remains unclear., Purpose: To explore the association between level of physical activity and sleep patterns in toddlers and preschool-age children with epilepsy., Methods: A cross-sectional, descriptive, correlational study was conducted. Ninety-eight children with epilepsy (1.5-6 years old) wore an actigraph for seven days. Additional data were collected using a health information datasheet, Children's Sleep Habits Questionnaire (CSHQ), and sleep diary, all of which were completed by the parents of each child., Results: The results showed that the mean amount of time spent in moderate-to-vigorous physical activity per day was 36.00 ± 49.20 minutes and that only 23 children (23.5%) had a nighttime sleep efficiency greater than 85%. The overall CSHQ score (56.00 ± 5.69) indicated the presence of moderate to severe sleep disturbances. Multiple regression analysis showed the hours and percentage of moderate-to-vigorous physical activity to be positively associated with night sleep efficiency (β = .54, p < .01; β = .51, p < .01) and negatively associated with nighttime sleep hours (β = -.55, p < .01; β = -.52, p < .01), even after controlling for potential confounders., Conclusions / Implications for Practice: Based on the findings, the sleep patterns and physical activity of children with epilepsy should be regularly assessed. Furthermore, appropriately increasing the duration of moderate-to-vigorous physical activity may improve sleep efficiency and prevent reductions in the duration of night sleep.

Rationale: Lacosamide (LCM) was initially approved in Taiwan in March 2014 for use as adjunctive therapy for focal impaired awareness seizures and secondarily generalized seizures (SGS) in patients with epilepsy ≥16 years of age. The efficacy and tolerability of adjunctive LCM for the treatment of patients with focal seizures have been demonstrated in randomized, placebo-controlled trials. However, the trials do not reflect a flexible dose setting. This study (EP0063) was conducted to assess the safety and tolerability of LCM in real-world clinical practice in Taiwan. Effectiveness of LCM was also assessed as an exploratory objective., Methods: EP0063 was a multicenter, prospective, noninterventional study with an expected observation period of 12 months ± 60 days. Eligible patients were ≥16 years of age, had focal impaired awareness seizures and/or SGS (in line with approved indication in Taiwan at the time of the study), were taking at least one concomitant antiseizure medication (ASM), and had at least one seizure in the 3 months before baseline. Patients were prescribed LCM by their treating physician in the course of routine clinical practice. The primary safety variable was treatment-emergent adverse events (TEAEs) spontaneously reported to, or observed by, the treating physician. Based on safety data from previous studies of LCM and known side effects of other ASMs, certain TEAEs (including but not limited to cardiac and electrocardiogram, suicidality, and rash related terms) were analyzed separately. Effectiveness variables included Clinical Global Impression of Change (CGIC) and change in 28-day seizure frequency from baseline to 12 months (or final visit), and freedom from focal seizures., Results: A total of 171 patients were treated with LCM, of whom 139 (81.3%) completed the study. The Kaplan-Meier estimated 12-month retention was 82.9%. Patients had a mean (standard deviation [SD], range) age of 38.5 (14.0, 16-77) years, and 96 (56.1%) were male. Patients were taking a mean (SD, range) of 2.8 (1.1, 1-6) ASMs at baseline. Mean (SD, range) duration of LCM treatment was 288.7 (111.9, 2-414) days, and the mean (SD, range) daily dosage of LCM was 205.0 (82.7, 50.0-505.2) mg/day. Overall, 95 (55.6%) patients reported at least one TEAE, most commonly dizziness (33 [19.3%] patients). Drug-related TEAEs were reported in 74 (43.3%) patients, and drug-related TEAEs leading to discontinuation of LCM were reported in 14 (8.2%) patients. Two (1.2%) patients died during LCM treatment, which were considered not related to LCM. Two (1.2%) patients had suicidality-related TEAEs; these TEAEs were considered either not related to LCM or the relationship was not recorded. Rash-related TEAEs were reported in five (2.9%) patients (considered LCM-related in two patients). Based on the CGIC, at 12 months (or final visit), 109 (63.7%) patients were considered to have improved, 54 (31.6%) had no change, and the remaining eight (4.7%) were minimally worse. At 12 months (or final visit), the median percentage change in focal seizure frequency was -50.0. During the first 6 months of the study, 21 (12.3%) patients were free from focal seizures; 37 (21.6%) patients were free from focal seizures in the last 6 months of the study; and 14 (8.2%) were free from focal seizures for the full 12 months of the study., Conclusions: Results of this prospective, noninterventional study suggest that adjunctive LCM was generally safe and well tolerated in this patient group in real-world practice in Taiwan. Effectiveness was also favorable, with more than 60% of patients considered to be improved by their physician at 12 months (or final visit)., Competing Interests: Declaration of competing interest Tony Wu, Yao-Chung Chuang, Hui-Chun Huang, Siew-Na Lim, Peiyuan F Hsieh, Wang-Tso Lee, Mei-Yun Cheng, Meng-Han Tsai, Shuo-Bin Jou, Chun-Wei Chang, and Hsiang-Yao Hsieh have no conflicts of interest to disclose. Xinlu Du was an employee of UCB Pharma at the time this study was conducted and is now an employee of Takeda. Scarlett Hellot is contracted by UCB Pharma for statistical services. Carrie McClung and Connie Hung are employees of UCB Pharma and receive UCB stocks., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 Sigma Theta Tau International.)

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., (© 2020 Wiley Periodicals, Inc.)

Study Objectives: To evaluate the effect of a clinic-based, behavioral-educational sleep intervention on sleep of children with epilepsy, maternal knowledge about childhood sleep, and maternal sleep quality., Methods: A total of 100 toddlers and preschool-age children with epilepsy (1.5-6 years, 55% boys) and their parents were randomized to receive sleep intervention (n = 50) or usual care with attention (n = 50). Outcomes were assessed at baseline, 3, 6, and 12 months after intervention with the use of objective actigraphy, Children's Sleep Habits Questionnaire, Parents' Sleep Knowledge Inventory, and Pittsburgh Sleep Quality Index. Intervention effects were examined using general linear models for repeated measurements to compare the mean change in outcomes from baseline to 12 months post-intervention between the two groups., Results: Sleep intervention resulted in children having greater sleep efficiency by 2.03% compared with the usual care group (95% CI = 0.20% to 3.86%; p = .03). Children in the intervention group also had significantly longer total nighttime sleep as objectively assessed by actigraphy than did those in the usual care group, with an adjusted mean difference of 16.13 minutes (95% CI = 0.24% to 32.03%; p = .04). No intervention effects were observed for maternal knowledge about childhood sleep, and maternal sleep quality., Conclusion: Sleep intervention provided during routine neurologic visits results in significant, measurable, and sustained benefits in sleep quality and quantity in children with epilepsy. Future trials are warranted to evaluate whether improvements in sleep could impact health-related quality of life or other aspects of functioning in children with epilepsy., Clinical Trial: This trial has been registered at www.clinicaltrials.gov (trial name: Sleep Intervention for Pediatric Epilepsy; registration number: NCT02514291)., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: Patients with Rett syndrome (RTT) present characteristic regression in communication and hand skills, which eventually leads to intellectual and physical disability. Moreover, caregivers of patients with RTT face stressors related to patients' medical and developmental concerns. Given the indications from case reports, this pilot study investigated the effectiveness of music therapy on RTT patients, as well as on parental stress for families of children with RTT., Methods: Families in the study group were enrolled in a twice-weekly 120-minute music therapy program for 24 weeks (n = 11), whereas families in the control group did not receive music therapy (n = 12). Participants were administered the Vineland Adaptive Behavior Scales, Rett Syndrome Clinical Severity Scale, Rett Syndrome Motor Behavioral Assessment, and Parenting Stress Index for caregivers of RTT children before and after the music therapy program., Results: Music therapy improved receptive language, verbal and non-verbal communication skills, and social interaction for RTT patients. In addition, purposeful hand function, breathing patterns, and eye contact were significantly improved. Of note, music therapy also decreased the frequency of epileptic seizures. Lastly, caregivers in the study group exhibited significantly lower stress following the program., Conclusion: The 24-week music therapy program was effective in improving social interaction, communication skills, eye contact, hand function, and reducing seizure frequency among RTT patients. Additionally, music therapy was effective in relieving parenting stress, which may help healthcare providers initiate early intervention strategies that can prevent parenting stress and reduce the risk of depression., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Study Objectives: To examine maternal knowledge of childhood sleep and its relation to sleep quantity, quality, and variability in a clinic sample of mothers of toddlers and preschool-age children with epilepsy., Methods: A total of 112 epileptic children wore a wrist actigraphy to objectively assess daily sleep duration and its variability across 7 days. Mothers completed the Parents' Sleep Knowledge Inventory and Children's Sleep Habits Questionnaire (CSHQ). Multivariate linear regression models were performed to predict CSHQ sleep disturbance scores, daily sleep duration, and daily sleep duration variability in children with epilepsy., Results: On average, mothers answered 30.5 per cent of the questions correctly about normal childhood sleep patterns. Only six (5.3%) of the mothers answered half or more of the questions correctly. Mothers more frequently answered "don't know" to questions about dreams, symptoms of sleep-disordered breathing, and adequate amounts of sleep required by children and adolescents. After adjusting for the child's age, gender, bed-sharing, and relevant clinical and epilepsy variables, poorer maternal sleep knowledge was the independent predictor of higher CSHQ sleep disturbance scores and greater intraindividual variability of daily sleep duration in epileptic children (p < 0.05)., Conclusions: Maternal knowledge about childhood sleep is inadequate and decreased maternal sleep knowledge is associated with poorer and more variable sleep in children with epilepsy. Findings from this study document the need to provide parental education about childhood sleep, particularly emphasizing the recommended sleep duration for children across different developmental stages and addressing the symptoms of sleep disorders commonly comorbid with epilepsy., Trial Registration: This trial has been registered at www.clinicaltrials.gov (trial name: Sleep Intervention for Pediatric Epilepsy; registration number: NCT02514291).

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., (© 2017 Sigma Theta Tau International.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Epilepsy in children is occasionally associated with variable comorbidities although the frequency of such comorbidity is often difficult to determine. They can be divided into three categories: neurological, psychological, and physical comorbidities. The goal of the present review is to discuss the reported comorbidities of epilepsy in children. The possible mechanisms and associated risk factors-including the effect of seizure frequency and seizure control, types of epilepsy, age of seizure onset, duration of illness, and the possible detrimental effect of antiepileptic drugs-will be described., (Copyright © 2015. Published by Elsevier B.V.)

Background and Purpose: Early-onset seizures are common in children with arterial ischemic stroke, but the clinical features and effects on the outcome of early-onset seizures have been less studied in children., Methods: Children aged 1 month to 18 years presenting with first-time and image-confirmed arterial ischemic stroke were identified for analysis., Results: A total of 78 survivors of arterial ischemic stroke were enrolled. Twenty (25.6%) had early-onset seizures, and 90% were initial presentation. Younger children (mean, 3.4±3.9 versus 9.0±6.2 years; P<0.001) and cortical involvement (5% versus 63.8%; P=0.01) are more likely to have early-onset seizures. Thirteen of 20 survivors with early-onset seizures had late-onset seizures after the acute stage, and 12 of them were diagnosed as poststroke epilepsy., Conclusions: Early-onset seizures occurred in 25.6% of children with arterial ischemic stroke. Younger age and cortical involvement were risk factors for early-onset seizures. Sixty-five percent of children with early-onset seizures had late-onset seizures after the acute stage.

Background/purpose: Little is known about whether Asian children with epilepsy have more attention-deficit hyperactivity disorder (ADHD)-related symptoms, emotional/ behavioral problems, and physical conditions compared with those described in Western studies. The authors investigated the rates of ADHD-related symptoms, emotional/behavioral problems, and physical conditions among pediatric patients with epilepsy., Methods: We recruited 61 patients with epilepsy, aged 6-16 years, and 122 age-, sex-, and parental education-matched school controls. Data on demographics, parental reports on the Child Behavior Checklist (CBCL) and Swanson, Nolan, and Pelham, version IV scale (SNAP-IV), and medical records were collected., Results: The average full-scale intelligence quotient of the case group was 95.8. There were 11 (18.0%), 7 (11.5%), 26 (42.6%), and 26 (42.6%) of children with epilepsy ever clinically diagnosed with developmental delay, overt ADHD symptoms, allergies reported by physicians, and behavior problems measured by the CBCL, respectively. Those children with epilepsy had more severe ADHD-related symptoms and a wider range of emotional/behavioral problems than controls (Cohen's d 0.36-0.80). The rate of potential cases of ADHD among children with epilepsy was 24.6%. A history of developmental delay predicted ADHD- related symptoms and internalizing and externalizing problems. Among children with epilepsy, a longer duration of treatment with antiepileptic drugs predicted externalizing problems, and an earlier onset of epilepsy predicted inattention and hyperactivity/impulsivity., Conclusion: Our findings imply that clinicians should assess physical and emotional/behavioral problems among children with epilepsy in order to provide interventions to offset possible adverse psychiatric outcomes., (Copyright © 2012. Published by Elsevier B.V.)

Seizures are a common presenting manifestation in children with disorders of amino acid metabolism. However, seizures may be very common in some specific diseases, but are rare in other diseases. In patients with classical maple syrup urine disease (MSUD), seizures commonly occur in the neonatal stage. But in intermittent or intermediate MSUD, seizures may develop in a later stage, or are uncommon. Patients with nonketotic hyperglycinemia often present with early myoclonic encephalopathy in the first weeks of life. However, in patients with atypical variants, seizures may be rare. In addition, patients with sulfite oxidase deficiency, serine deficiency, or GABA-related disorders may also present with different types of seizures. In monoamine biosynthesis disorders, seizures are rare, but paroxysmal dystonia is frequently misdiagnosed as seizures. Therefore, the incidence of seizures in disorders of amino acid metabolism is variable. Timely diagnosis and early treatment may improve the prognosis of these disorders., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: to investigate the attentional processes and symptoms of attention-deficit hyperactivity disorder (ADHD) in pediatric patients with epilepsy and IQ greater than 70 in Taiwan., Methods: we assessed 61 children (male, 62.3%; full-scale IQ >70) with epilepsy, ages 6-16 years, and 61 sex-, age-, and parental education-matched typically developing children (controls). All participants completed the intelligence (WISC-III) and attention assessments (Conners' Continuous Performance Test, CPT). The parents reported on the ADHD symptoms of their children., Results: children with epilepsy had more omission errors and deviant response style (β) and scored lower in the Hit Reaction Time (RT) Block Change, reflecting inattention and slowness. Epileptic children with ADHD symptoms had longer and more variable Hit RT than those without ADHD and controls. Higher full-scale IQ was significantly associated with less change in Hit RT, Hit RT block, standard error, and inter-stimulus intervals. There were no effects from age of onset, duration of having epilepsy, etiology of epilepsy, and brain anomaly on the CPT profiles., Conclusion: the findings suggest that children with epilepsy, despite not mentally retarded, may have attention deficits. Hence, screening for attention problems among patients with epilepsy regardless of intelligence level and ADHD symptoms is recommended to offset possible learning adversities of this population., (2010 Elsevier B.V. All rights reserved.)

To identify clinical, neurophysiological and neuroradiological features in acute encephalitis with predictive value for postencephalitic epilepsy (PEE) in children, a retrospective cohort study by following up 0-17-year-old children with the diagnosis of acute encephalitis was done. Total 330 children were enrolled. Of these, 54 (16.4%) developed epilepsy with a mean follow-up period of 6+/-4.6 years, and 79.6% had the diagnosis of epilepsy within six months after encephalitis. Significant risk factors for PEE include the presence of recurrent seizures, status epilepticus, severe disturbance of consciousness, the existence of focal neurological sign, and the presence of neurological deterioration during hospitalization. Patients with abnormal electroencephalogram, including focal (P<0.05), or profound cerebral dysfunction (P<0.001), and focal cortical abnormalities in neuroimaging (P<0.01), also have higher incidence of epilepsy. Furthermore, children with refractory status epilepticus at presentation also significantly increased the possibility of intractable PEE (P<0.01). We concluded that PEE is not a rare complication of acute encephalitis. Children with refractory status epilepticus or poor control of seizures are more likely to have intractable PEE.

Sleep problems are prevalent among individuals with Rett syndrome. We aimed to investigate sleep problems in individuals with Rett syndrome and their caregivers. A total of 29 participants diagnosed with Rett syndrome and their respective 29 caregivers were included. The Children Sleep Habits Questionnaire (CSHQ), the Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiologic Studies Depression Scale (CES-D), and the actigraphy data collected from Actiwatch 2 were used to investigate the change of sleep pattern. Based on the CSHQ questionnaire, 75.9% (22/29) of the patients reported sleep disturbances. The younger patients exhibited higher CSHQ scores. Actigraphy data revealed that both young and older patients had short total sleep duration, low sleep efficiency, long sleep-onset latency, long awaking duration, and fragmented sleep. The caregivers reported significantly higher PSQI scores, mildly declined sleep efficiency, and shorter total sleep duration in the actigraphy study. Associations were identified between smaller head circumference and shorter total sleep duration, more severe motor dysfunction and longer wake after sleep onset, worsen scoliosis and more awakenings per night. Sleep efficiency was inversely associated with epilepsy and positively associated with somatic growth. Sleep disturbances are common and should be investigated in individuals with Rett syndrome and their caregivers. Sleep problems are common and impactful among individuals with Rett syndrome (RTT) and their caregivers. We examined the sleep patterns of 29 RTT patients and their primary caregivers using various assessment tools. The study found that a majority of the patients experienced sleep disturbances, with younger patients showing more sleep difficulties. Caregivers also reported poor sleep quality. The findings emphasize the need to address sleep problems in RTT management, as improving sleep quality can positively impact the well-being of individuals with RTT and their caregivers. [ABSTRACT FROM AUTHOR]

Genetic mutations in TBC1D24 have been associated with multiple phenotypes, with epilepsy being the main clinical manifestation. The TBC1D24 protein consists of the unique association of a Tre2/Bub2/Cdc16 (TBC) domain and a TBC/lysin motif domain/catalytic (TLDc) domain. More than 50 missense and loss-of-function mutations have been described and are spread over the entire protein. Through whole genome/exome sequencing we identified compound heterozygous mutations, R360H and G501R, within the TLDc domain, in an index family with a Rolandic epilepsy exercise-induced dystonia phenotype (http://omim.org/entry/608105). A 20-year long clinical follow-up revealed that epilepsy was self-limited in all three affected patients, but exercise-induced dystonia persisted into adulthood in two. Furthermore, we identified three additional sporadic paediatric patients with a remarkably similar phenotype, two of whom had compound heterozygous mutations consisting of an in-frame deletion I81_K84 and an A500V mutation, and the third carried T182M and G511R missense mutations, overall revealing that all six patients harbour a missense mutation in the subdomain of TLDc between residues 500 and 511. We solved the crystal structure of the conserved Drosophila TLDc domain. This allowed us to predict destabilizing effects of the G501R and G511R mutations and, to a lesser degree, of R360H and potentially A500V. Next, we characterized the functional consequences of a strong and a weak TLDc mutation (TBC1D24G501R and TBC1D24R360H) using Drosophila, where TBC1D24/Skywalker regulates synaptic vesicle trafficking. In a Drosophila model neuronally expressing human TBC1D24, we demonstrated that the TBC1D24G501R TLDc mutation causes activity-induced locomotion and synaptic vesicle trafficking defects, while TBC1D24R360H is benign. The neuronal phenotypes of the TBC1D24G501R mutation are consistent with exacerbated oxidative stress sensitivity, which is rescued by treating TBC1D24G501R mutant animals with antioxidants N-acetylcysteine amide or α-tocopherol as indicated by restored synaptic vesicle trafficking levels and sustained behavioural activity. Our data thus show that mutations in the TLDc domain of TBC1D24 cause Rolandic-type focal motor epilepsy and exercise-induced dystonia. The humanized TBC1D24G501R fly model exhibits sustained activity and vesicle transport defects. We propose that the TBC1D24/Sky TLDc domain is a reactive oxygen species sensor mediating synaptic vesicle trafficking rates that, when dysfunctional, causes a movement disorder in patients and flies. The TLDc and TBC domain mutations' response to antioxidant treatment we observed in the animal model suggests a potential for combining antioxidant-based therapeutic approaches to TBC1D24-associated disorders with previously described lipid-altering strategies for TBC domain mutations. [ABSTRACT FROM AUTHOR]

Background: Microglia is responsible for neuroinflammation, which may aggravate brain injury in diseases like epilepsy. Mammalian target of rapamycin (mTOR) kinase is related to microglial activation with subsequent neuroinflammation. In the present study, rapamycin and everolimus, both as mTOR inhibitors, were investigated in models of kainic acid (KA)-induced seizure and lipopolysaccharide (LPS)-induced neuroinflammation.Methods: In vitro, we treated BV2 cells with KA and LPS. In vivo, KA was used to induce seizures on postnatal day 25 in B6.129P-Cx3cr1tm1Litt/J mice. Rapamycin and everolimus were evaluated in their modulation of neuroinflammation detected by real-time PCR, Western blotting, and immunostaining.Results: Everolimus was significantly more effective than rapamycin in inhibiting iNOS and mTOR signaling pathways in both models of neuroinflammation (LPS) and seizure (KA). Everolimus significantly attenuated the mRNA expression of iNOS by LPS and nitrite production by KA and LPS than that by rapamycin. Only everolimus attenuated the mRNA expression of mTOR by LPS and KA treatment. In the present study, we also found that the modulation of mTOR under LPS and KA treatment was not mediated by Akt pathway but was primarily mediated by ERK phosphorylation, which was more significantly attenuated by everolimus. This inhibition of ERK phosphorylation and microglial activation in the hippocampus by everolimus was also confirmed in KA-treated mice.Conclusions: Rapamycin and everolimus can block the activation of inflammation-related molecules and attenuated the microglial activation. Everolimus had better efficacy than rapamycin, possibly mediated by the inhibition of ERK phosphorylation. Taken together, mTOR inhibitor can be a potential pharmacological target of anti-inflammation and seizure treatment. [ABSTRACT FROM AUTHOR]

Epilepsy in children is occasionally associated with variable comorbidities although the frequency of such comorbidity is often difficult to determine. They can be divided into three categories: neurological, psychological, and physical comorbidities. The goal of the present review is to discuss the reported comorbidities of epilepsy in children. The possible mechanisms and associated risk factors-including the effect of seizure frequency and seizure control, types of epilepsy, age of seizure onset, duration of illness, and the possible detrimental effect of antiepileptic drugs-will be described. [ABSTRACT FROM AUTHOR]

Epileptic encephalopathy with suppression-burst in electroencephalography (EEG) can evolve into a few types of epileptic syndromes. We present here an unusual case of early myoclonic encephalopathy that evolved into migrating partial seizures in infancy. A female neonate initially had erratic myoclonus movements, hiccups, and a suppression-burst pattern in EEG that was compatible with early myoclonic encephalopathy. The seizures were controlled with dextromethorphan (20 mg/kg), and a suppression-burst pattern in EEG was reverted to relatively normal background activity. However, at 72 days of age, alternating focal tonic seizures, compatible with migrating partial seizures in infancy, were demonstrated by the 24-hour EEG recording. The seizures responded poorly to dextromethorphan. To our knowledge, this is the first reported case of early myoclonic encephalopathy evolving into migrating partial seizure in infancy. Whether it represents another age-dependent epilepsy evolution needs more clinical observation. [ABSTRACT FROM AUTHOR]

Abstract: This study aimed to examine sleep problems in children with autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), and epilepsy in clinical settings. We assessed 64 children with ASD, 64 with ADHD, 64 with epilepsy, and 64 typically developing children without any neuropsychiatric disorders by using a sex-and age-matched case–control study design. The parents reported their children''s sleep problems. Parents of children with ASD and ADHD reported more current and lifetime sleep problems of their children than parents of children with epilepsy, especially in snoring and restless legs syndrome. Current or lifetime sleep problems did not differ between children with ASD and children with ADHD, or between children with epilepsy and typically developing children. Demographic characteristics and medication status could not fully explain the increased risk of sleep problems in children with ASD and ADHD. Our findings lend evidence to support more sleep problems in children with ASD and ADHD than typically developing children. Our study adds that children with epilepsy do not. These findings emphasize the importance to assess sleep problems in children with neurodevelopmental disorders highly comorbid with ASD or ADHD in clinical practice. [Copyright &y& Elsevier]

The diagnosis of benign epilepsy syndrome should meet the following criteria: age-related and self-limited; good response to medication; and no obvious neurological sequelae after seizure. However, the current concept of benign epilepsy syndrome has been challenged because of the advancements in genetic studies, neuroimaging, and molecular techniques. Many studies have revealed that the prevalence of behavioral problems and learning difficulties as well as subtle cognitive deficits is higher among patients with benign epilepsy, compared with the normal population. Here, we review updated results of these studies to show the latest and broad comprehensive knowledge of benign epilepsy in children. [Copyright &y& Elsevier]

The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The γ-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures. [Copyright &y& Elsevier]

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]

• The total EEG complexity is a potential biomarker of infantile spasms. • Higher total EEG complexity before AED and 6 months after ACTH is associated with spasm-freedom. • The total EEG complexity is not associated with the presence of hypsarrhythmia. To investigate the potential of EEG multiscale entropy and complexity as biomarkers in infantile spasms. We collected EEG data retrospectively from 16 newly diagnosed patients, 16 age- and gender-matched healthy controls, and 15 drug-resistant patients. The multiscale entropy (MSE) and total EEG complexity before anti-epileptic drug (AED) treatment, before adrenocorticotropic hormone (ACTH) treatment, 14 days after ACTH therapy, and after 6 months of follow-up were calculated. The total EEG complexity of 16 newly diagnosed infantile spasms patients was lower than the 16 healthy controls (median [IQR]: 351.5 [323.1–388.1] vs 461.6 [407.7–583.4]). The total EEG complexity before treatment was higher in the six patients with good response to AED than the 10 patients without response (median [IQR]: 410.0 [388.1–475.0] vs 344.5 [319.6–352.0]). The total EEG complexity before and after 14-days of ACTH therapy was not different between 13 ACTH therapy responders and nine non-responders. After 6-months follow-up, the total EEG complexity of ACTH therapy responders were higher than non-responders (median [IQR]: 598.5 [517.4–623.3] vs 448.6 [347.1–536.3]). The total EEG complexity before AED and 6 months after ACTH are associated with spasm-freedom. The total EEG complexity is a potential biomarker to predict and monitor the treatment effect in infantile spasms. [ABSTRACT FROM AUTHOR]

Aim To assess the clinical trial and real-world data for adjunctive perampanel in adolescents and develop consensus recommendations to guide the use of perampanel in this population in clinical practice. Methods In May 2015, 15 epilepsy experts attended a Consensus Development Meeting to assess the clinical trial data for perampanel, specific to the adolescent age group (12-17 years) and develop consensus treatment recommendations. Results and Discussion Analysis of the adolescent subgroup data of three pivotal placebo-controlled, double-blind, phase 3 trials investigating perampanel in patients with ongoing focal epileptic seizures despite receiving one to three antiepileptic drugs found that perampanel 4-12 mg was superior to placebo. The tolerability profile of perampanel was generally acceptable. Adolescent patients receiving long-term treatment with perampanel in an open-label extension study maintained improvements in seizure control compared with baseline, with a favorable risk-benefit profile. A phase 2 study showed that perampanel had no clinically important effects on cognitive function, growth, and development. Conclusion Perampanel is a welcome addition to the armamentarium of existing antiepileptic drugs as it represents a new approach in the management of epilepsy, with a novel mechanism of action, and the potential to have a considerable impact on the treatment of adolescents with epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: PRRT2 mutations were recently identified in benign familial infantile epilepsy (BFIE) and infantile convulsions with paroxysmal choreoathetosis (ICCA) but no abnormalities have so far been identified in their phenotypically similar seizure disorder of benign convulsions with mild gastroenteritis (CwG), while mutations in KCNQ2 and KCNQ3 have been recognized in benign familial neonatal epilepsy (BFNE). The aim of this study was to identify PRRT2 mutations in infantile convulsions in Asian families with BFIE and ICCA, CwG and BFNE. Methods: We recruited 26 unrelated Japanese affected with either BFIE or non-familial benign infantile seizures and their families, including three families with ICCA. A total of 17 Japanese and Taiwanese with CwG, 50 Japanese with BFNE and 96 healthy volunteers were also recruited. Mutations of PRRT2 were sought using direct sequencing. Results: Heterozygous truncation mutation (c.649dupC) was identified in 15 of 26 individuals with benign infantile epilepsy (52.1%). All three families of ICCA harbored the same mutation (100%). Another novel mutation (c.1012+2dupT) was found in the proband of a family with BFIE. However, no PRRT2 mutation was found in either CwG or BFNE. Conclusions: The results confirm that c.649dupC, a truncating mutation of PRRT2, is a hotspot mutation resulting in BFIE or ICCA regardless of the ethnic background. In contrast, PRRT2 mutations do not seem to be associated with CwG or BFNE. Screening for PRRT2 mutation might be useful in early-stage differentiation of BFIE from CwG. [Copyright &y& Elsevier]

We investigated the clinical characteristics of children with continuous spike waves during slow-wave sleep syndrome and their treatment response to levetiracetam. Five boys and one girl, diagnosed with epilepsy with continuous spike waves during slow-wave sleep syndrome, were enrolled. Their clinical characteristics, including neuroimaging findings, were reviewed. The signs related to continuous spike waves during slow-wave sleep included increased seizure frequency (6/6), impaired responsiveness (3/6), and psychomotor regression (2/6). Magnetic resonance imaging disclosed lissencephaly in one patient, and porencephaly of the left hemisphere in another. The number of antiepileptic drugs before the use of levetiracetam was 0-4 (mean ± SD, 2.3 ± 1.5). Five of 6 children demonstrated a good response to levetiracetam, whereas 2 (40%) underwent a relapse of electrical status epilepticus during sleep pattern on electroencephalograms 4 and 5 months after clinical improvement. Both were 5 years old. The most common presenting sign in children with continuous spike waves during slow-wave sleep syndrome is increasing seizure frequency. Levetiracetam is effective in treating children with continuous spike waves during slow-wave sleep syndrome. However, the relapse rate of continuous spike waves during slow-wave sleep syndrome remains high in young children. [Copyright &y& Elsevier]

Occipital lobe epilepsy in children can present as an idiopathic form (i.e., childhood epilepsy with occipital paroxysms) or as a symptomatic form. Forty-three children (18 boys, 25 girls) were divided into the idiopathic group or symptomatic group, according to the classification for epileptic seizures of the International League Against Epilepsy. Patients in the idiopathic group were further subdivided into the Panayiotopoulos or Gastaut type, according to clinical presentation. The idiopathic group consisted of 15 children (5 boys, 10 girls), of whom 11 were of the Panayiotopoulos type and 4 of the Gastaut type. The symptomatic group consisted of 28 children (13 boys, 15 girls). The average age of seizure onset in the idiopathic group was younger than in the symptomatic group (6.5 ± 2.4 vs 8.5 ± 3.0 years). Ictal vomiting was more common in the idiopathic group, and positive visual symptoms were more common in the symptomatic group. Mean epilepsy duration in the idiopathic group was shorter (5.7 ± 5.3 vs 20.1 ± 16.0 months), and the response to treatment was better. The average age of seizure onset was much younger in the Panayiotopoulos than in the Gastaut type (5.4 ± 1.5 vs 9.5 ± 1.5 years), and mean epilepsy duration was also shorter (3.9 ± 4.2 vs 10.5 ± 4.9 months). Seizure semiology can distinguish between idiopathic occipital lobe epilepsy and the symptomatic form with ictal vomiting and positive visual symptoms. In idiopathic occipital lobe epilepsy, the Panayiotopoulos type has better prognosis than the Gastaut type. [Copyright &y& Elsevier]

An 8-year-3-month-old male with right porencephaly and epilepsy was found to have skin rash 2 weeks after the beginning of treatment with lamotrigine. One month later he suffered from impaired liver function and pancytopenia in the presence of hypocellular bone marrow with hemophagocytosis. No evidence of infection was evident. Intravenous immunoglobulin and steroid were administered with discontinuation of lamotrigine; the hemogram and liver function profile improved dramatically. Hemophagocytic syndrome should be considered a possible cause of pancytopenia in patients taking new antiepileptic drugs such as lamotrigine. [Copyright &y& Elsevier]