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Objective: To investigate the surgical outcomes of patients with drug-resistant epilepsy and bilateral brain magnetic resonance imaging (MRI) abnormalities who had undergone various epilepsy surgeries., Methods: Patients with drug-resistant epilepsy and bilateral brain abnormalities on MRI who underwent epilepsy surgery at the Severance Children's Hospital between October 2003 and December 2021 were included. The age of seizure onset was 18 years or younger. Engel's classification was used to assess seizure outcomes at 1, 2, and 5 years after surgery., Results: A total of 40 patients met the inclusion criteria. The median age at surgery was 10.9 years (interquartile range [IQR] 6.9-15.1); the median interval to surgery was 7.1 years (IQR 2.7-11.5). One year after surgery, a favorable outcome of Engel class I-II was observed in 53% (21/40) of patients. At the 2- and 5-year follow-ups, 56% (20/36) and 63% (17/27) of patients showed good postoperative outcomes, respectively., Conclusions: Approximately, half of the patients with bilateral brain MRI abnormalities achieved seizure freedom after epilepsy surgery. The existence of bilateral brain MRI abnormalities should not hinder resective epilepsy surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study determined the 24-month outcomes of perampanel treatment in children and adolescents with epilepsy. The percentage of ≥ 50% responders was 47.3% (139/294) at 12 months and 49.0% (144/294) at 24 months. A 100% reduction in seizures for more than 12 months was observed in 12.2% (36/294). Discontinuation occurred in 39.8% (117/294). The most common reason for discontinuation was adverse events (29.1%, 34/117). Baseline seizure frequency was higher in children aged < 12 years than in patients aged ≥ 12 years; however, the percentage of seizure reduction and ≥ 50% responders did not significantly differ between the two groups. The rate of early discontinuation was higher (p < 0.001) and the duration of perampanel treatment was shorter in children aged < 12 years (p = 0.001). Most children aged < 12 years discontinued PER due to inadequate effectiveness, while adverse event was the most common reason in patients aged ≥ 12 years (p = 0.045). Only slow titration was significantly associated with ≥ 50% of responders. In conclusion, this study showed that perampanel can be utilized effectively and safely for a prolonged period in pediatric patients aged 4 to < 12 years, as well as in patients aged 12 years and older., (© 2023. Springer Nature Limited.)

Purpose: We evaluated self-reported psychopathology in adolescents with epilepsy (AWE) and determined which types of psychopathology were associated with the parental perception of stigma towards AWE., Methods: This was a cross-sectional, multicenter study of 289 adolescents aged 11 to 18 years. Psychopathology was evaluated using the Youth Self-Report scale, which consists of eight narrowband and three broadband syndrome scales. We analyzed the raw score and T-score of each syndrome scale. The parental perception of stigma was assessed using the modified three-item Epilepsy Stigma Scale., Results: Of the 289 AWE (180 boys and 109 girls), 18.3% had at least one emotional or behavioral problem in the clinical range. Social problems were the most common (10.0%), followed by attention problems (6.9%) and aggressive behaviors (4.2%). Externalizing problems (11.8%) were two times more common than internalizing problems (6.2%). Females and older AWE had a higher level of internalizing problems. Social problems were more common in girls (15.6%) than in boys (6.7%), whereas thought problems were more common in boys (3.9%) than in girls (0%). Epilepsy-related factors, especially antiseizure medication polytherapy, were significantly associated with various emotional and behavioral problems. A quarter of parents felt stigma towards their children with epilepsy. Male sex, antiseizure medication polytherapy, and longer duration of epilepsy were more likely to be associated with the parental perception of stigma. Parental perception of stigma was significantly associated with psychopathology in AWE, particularly externalizing problems and social problems., Conclusions: Emotional and behavioral problems in AWE are common and vary depending on demographic, clinical, and parental factors. Early identification and proper management of these problems are crucial for decreasing comorbid psychopathology in AWE., 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 © 2022 Elsevier Inc. All rights reserved.)

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet, in which fat, instead of glucose, acts as a major energy source through the production of ketone bodies. The KD was formally introduced in 1921 to mimic the biochemical changes associated with fasting and gained recognition as a potent treatment for pediatric epilepsy in the mid-1990s. Recent clinical and scientific knowledge supports the use of the KD in drug-resistant epilepsy patients for its anti-seizure efficacy, safety, and tolerability. The KD is also receiving growing attention as a potential treatment option for other neurological disorders. This article will review on the recent updates on the KD, focusing on its mechanisms of action, its alternatives, expansion on its use in terms of age groups and different regions in the world, and future issues., Competing Interests: Conflicts of interest There is no competing interest among the authors., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Purpose: The observation of mild malformation of cortical development (mMCD) has yet to have a major clinical impact due to the lack of clinical and research data. We characterized the clinical features, surgical outcomes, and postoperative seizure control patterns in pediatric patients with mMCD., Methods: We examined 40 patients with isolated mMCD who underwent resective surgery during a 10-year period., Results: The median age at seizure onset was 1.2 years, and the median age at surgery was 7.9 years. Twenty-seven patients (67.5%) presented with childhood-onset epileptic encephalopathy (21 Lennox-Gastaut syndrome, 6 West syndrome), and 13 patients (32.5%) presented with intractable focal epilepsy (10 extratemporal lesions, 3 temporal lesions). Twenty-one patients (52.5%) showed "suspected focal cortical malformation" on MRI, whereas 16 patients (40.0%) and 3 patients (7.5%) showed normal MRI findings or mild brain atrophy, respectively. The most common surgical procedures were two lobar resections (18 patients, 45.0%), followed by unilobar resections (12 patients, 30.0%) and resections exceeding two lobar boundaries (10 patients, 25.0%). As a final surgical outcome, 24 patients (60.0%) were ILAE Class 1-3. Discontinuation of all AEDs was possible for 36.8% of ILAE Class 1 patients. Regarding the seizure control pattern, fluctuating seizure control was observed most frequently (21 patients, 52.5%)., Conclusion: Our results suggest that mMCD is an important pathological finding in children related to a significant degree of epileptogenicity, and resective surgery can have positive outcomes. However, these patients showed unstable postoperative seizure control patterns with a high rate of late recurrence, suggesting difficulties in the surgical treatment of intractable epilepsy., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: For epilepsy with tuberous sclerosis complex (TSC), ketogenic diet (KD) therapy has been consistently reported to be more beneficial than the average KD therapy response. Herein, we aimed to investigate the long-term outcomes of a KD on patients with TSC and intractable epilepsy., Methods: This study included 31 patients with intractable epilepsy and TSC who were treated with the KD, and an intention-to-treat analysis was performed., Results: Overall, 21 of the 31 patients (67.7%) had >50% reduction in seizures at 3 months after initiating the KD. Thirteen of the 31 patients (41.9%) were seizure-free for at least 3 months, but 10 of these 13 patients (76.9%) experienced seizure recurrence during the 24-month follow-up period. Finally, at 24 months of the KD observational period, there was >50% response in 10 of the 31 patients (32.3%), including seizure-free patients (6 of 31 patients, 19.4%). Most of the patients (12 of 13, 92.3%) who experienced seizure freedom had >50% reduction in seizures within 1 month after initiating the KD, and this result was the only factor associated with seizure freedom in the current study., Conclusion: The KD appeared to be an effective therapeutic modality for intractable pediatric epilepsy in TSC, but it did not exhibit guaranteed efficacy over a long-term period., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose relevant to this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: We aim to delineate the genetic and clinical features of SCN8A developmental and epileptic encephalopathy., Methods: Nine patients with SCN8A developmental and epileptic encephalopathy were included in this study. Genetic and clinical features and effectiveness of sodium channel blockers were assessed in patients who were confirmed with SCN8A mutations., Results: The onset of seizures ranged from the neonatal period to 18 months of age. Seizure types were diverse and predominantly involved focal seizures or spasms. The most common initial epilepsy syndrome was West syndrome in four patients, followed by neonatal-onset focal seizures in three patients and unclassified focal epilepsy in two patients. Electroencephalograms (EEGs) showed slow and disorganized background and epileptiform abnormalities with occipital predominance. Six patients presented intractable seizures including one patient with recurrent nonconvulsive status epilepticus. Sodium channel blockers were effective in seven patients among eight patients given them. All patients showed developmental delay or regression. Severe hypotonia or ataxia was also presented in some patients. Microcephaly was also characteristic. De novo missense mutations in SCN8A were found in the inactivation gate, C-terminal, loop 2, and transmembrane segments (S1, 4, 5, and 6). There was no correlation between the location of the mutation in the protein and phenotype or response to sodium channel blockers., Conclusion: SCN8A developmental and epileptic encephalopathy presents intractable seizures including spasms, focal seizures, neonatal status epilepticus, and nonconvulsive status epilepticus. Sodium channel blockers were effective irrelevant to the location of the mutation in the protein., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: It is important to determine whether specific etiology is more effective to dietary treatment so that the diet can be started earlier for infants. We evaluated etiology-specific, seizure-free outcomes of dietary treatment in infants <1 year of age., Methods: We conducted a 10-year, retrospective, longitudinal observational study of 115 infants treated with ketogenic diet (KD) or modified Atkins diet (MAD)., Results: Most patients (70%) received classical KD; 30% received MAD. During follow-up, 90%, 73%, and 61% of the patients remained on the diet at 3, 6, and 12 months, respectively. Seizure-free outcomes were reported in 50%, 44%, and 50% of the patients at 3, 6, and 12 months, respectively. Long-term seizure-free outcomes over 12 months were reported in 43 (74%) of 58 infants who were seizure-free at 3 months. Etiologies were mostly symptomatic (structural brain abnormalities, genetic, or metabolic) in 83 (72%) of 115 patients. According to underlying etiology, long-term seizure-free outcomes were observed in 14 (33%) of 42 patients with structural brain abnormalities, 7 (33%) of 21 with genetic etiologies, 7 (35%) of 20 with metabolic etiologies, and 15 (47%) of 32 with unknown etiologies. There were no etiology-based differences with respect to long-term seizure-free outcomes (P = 0.63)., Conclusion: The high rate of long-term seizure-free outcomes can be predicted based on the seizure freedom at 3 months regardless of etiology. Early dietary treatment is beneficial, even in infants <1 year of age with specific symptomatic etiologies such as genetic, structural brain abnormalities, and metabolic etiology., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Low-grade epilepsy-associated tumors (LEATs) are associated with childhood seizures that are typically drug-resistant, necessitating surgical interventions. In this study, we aimed to investigate the efficacy of surgical intervention in children with LEATs and to identify factors associated with seizure and cognitive outcomes., Methods: We reviewed 58 children less than 18 years of age who underwent epilepsy surgery due to histopathologically confirmed LEATs and had a minimum postoperative follow-up duration of 24 months., Results: Of the 58 patients who were followed for a median duration of 5.6 (IQR 3.2 to 10.0) years, 51 (87.9%) were seizure-free after surgery. In univariate analysis, shorter epilepsy duration, fewer antiepileptic drugs at time of surgery, gross total resection, and unilobar tumor involvement were associated with seizure freedom. In multivariate analysis, gross total resection was independently associated with seizure freedom. The preoperative and postoperative full-scale intelligence quotient (FSIQ) scores were 78.9 ± 27.1 and 80.9 ± 28.7, respectively. In univariate analysis, younger age at seizure onset, longer epilepsy duration, more antiepileptic drugs at time of surgery, multilobar tumor involvement, and presence of generalized epileptic discharges were associated with lower preoperative FSIQ. In multivariate analysis, longer epilepsy duration was independently associated with lower preoperative FSIQ scores. Postoperative FSIQ scores were significantly influenced by preoperative FSIQ scores., Conclusions: Epilepsy surgery for LEATs in children resulted in excellent seizure outcome. Gross total resection was the only independent factor associated with favorable seizure outcome. Preoperative and postoperative cognitive abilities were significantly influenced by epilepsy duration, so early surgical intervention should be considered., (Copyright © 2018. Published by Elsevier Inc.)

Background: We intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation sequencing (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing the diagnosis rate., Methods: We assessed 74 patients with EOE whose seizures started before 3 years of age using a customized NGS panel that included 172 genes. Single nucleotide variants (SNVs) and exonic and chromosomal copy number variations (CNVs) were intensively examined with our customized pipeline and crosschecked with commercial or pre-built software. Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Each case was further discussed in a monthly consensus meeting that included the participation of all laboratory personnel, bioinformaticians, geneticists, and clinicians., Results: The NGS panel identified 28 patients (37.8%) with genetic abnormalities; 25 patients had pathogenic or likely pathogenic SNVs in 17 genes including SXTBP1 (n = 3), CDKL5 (n = 2), KCNQ2 (n = 2), SCN1A (n = 2), SYNGAP1 (n = 2), GNAO1 (n = 2), KCNT1 (n = 2), BRAT1, WWOX, ZEB2, CHD2, PRICKLE2, COL4A1, DNM1, SCN8A, MECP2, SLC9A6 (n = 1). The other 3 patients had pathogenic CNVs (2 duplications and 1 deletion) with varying sizes (from 2.5 Mb to 12 Mb). The overall diagnostic yield was 37.8% after following our step-by-step approach for clinical consensus., Conclusions: NGS is a useful diagnostic tool with great utility for patients with EOE. Diagnostic yields can be maximized with a standardized and team-based approach.

Focal cortical dysplasia (FCD) is a major cause of the sporadic form of intractable focal epilepsies that require surgical treatment. It has recently been reported that brain somatic mutations in MTOR account for 15%-25% of FCD type II (FCDII), characterized by cortical dyslamination and dysmorphic neurons. However, the genetic etiologies of FCDII-affected individuals who lack the MTOR mutation remain unclear. Here, we performed deep hybrid capture and amplicon sequencing (read depth of 100×-20,012×) of five important mTOR pathway genes-PIK3CA, PIK3R2, AKT3, TSC1, and TSC2-by using paired brain and saliva samples from 40 FCDII individuals negative for MTOR mutations. We found that 5 of 40 individuals (12.5%) had brain somatic mutations in TSC1 (c.64C>T [p.Arg22Trp] and c.610C>T [p.Arg204Cys]) and TSC2 (c.4639G>A [p.Val1547Ile]), and these results were reproducible on two different sequencing platforms. All identified mutations induced hyperactivation of the mTOR pathway by disrupting the formation or function of the TSC1-TSC2 complex. Furthermore, in utero CRISPR-Cas9-mediated genome editing of Tsc1 or Tsc2 induced the development of spontaneous behavioral seizures, as well as cytomegalic neurons and cortical dyslamination. These results show that brain somatic mutations in TSC1 and TSC2 cause FCD and that in utero application of the CRISPR-Cas9 system is useful for generating neurodevelopmental disease models of somatic mutations in the brain., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Epileptic seizures in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) are heterogeneous with no pathognomonic features. We reviewed epilepsy characteristics and clinical outcome exclusively in a pediatric population., Methods: Twenty-two children and adolescents (13 males) with confirmed mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes due to mitochondrial DNA A3243G mutation and epilepsy were recruited. Clinical data including seizure semiology, treatment response, neuroimaging findings, and electroencephalography were analyzed. We also examined the effect of the age at seizure onset and initial symptoms on the clinical variables., Results: Seizure semiology and electroencephalography abnormalities showed no syndrome-specific findings. Focal seizures occurred in 21 of 22 subjects (95.5%), whereas generalized seizures developed in seven of 22 subjects (31.8%). Twenty of 22 subjects (90.9%) achieved partial to complete reduction of clinical seizures for more than one year with a combination of more than two antiepileptic drugs. The subgroup with earlier seizure onset presented significantly earlier and showed significantly higher rates of drug-resistant epilepsy compared with the late onset group, although there were no significant differences in the initial symptoms. The subjects with severe epileptic conditions tended to have more severe clinical dysfunction and more severe organ involvement., Conclusions: Both focal and generalized seizures occurred in patients with MELAS. Epilepsy in this population is drug resistant, but a certain degree of clinical seizure reduction was achievable with antiepileptic drugs, with more favorable outcomes than historically expected. Close observation and active epilepsy treatment of individuals with MELAS episodes and earlier seizure onset might improve the prognosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate the feasibility of a 35-week exercise program and its efficacy on neurocognitive and psychological variables in children with benign epilepsy with centrotemporal spikes. Ten children with benign epilepsy with centrotemporal spikes (aged 8 to 12 years) completed a 35-week exercise program consisting of supervised sport activities for 5 weeks and home-based exercise program for 30 weeks. The children and their parents participated in neurocognitive and psychological evaluations including measures of attention, executive function, behaviors, and quality of life at baseline and postexercise follow-up at the 35th week. At postintervention evaluation, significant improvements were seen relative to baseline in neurocognitive domains such as psychomotor speed, sustained attention, divided attention, and inhibition-disinhibition ability, and in psychological domains including internalizing behavior problems, general health, and general quality of life. Long-term exercise intervention may have benefits for some aspects of neurocognitive and psychological function in children with benign epilepsy., (© The Author(s) 2016.)

Objective: To compare the seizure and developmental outcomes in infants and young children with epileptic encephalopathy who have undergone surgical and medical treatments., Methods: An international, multicenter, observational cohort study was undertaken. A total of 317 children aged <6 years, who had frequent disabling seizures despite intensive medical treatments, were registered. Among the enrolled children, 250 were treated medically (medical group), 31 underwent resective surgery (resective group), and 36 underwent palliative surgery [callosotomy (n=30) or vagal nerve stimulation (n=6); palliative group] on admission. Seizure and developmental outcomes were obtained for 230 children during the 3-year follow-up period. Cox proportional hazard model was used to adjust for clinical backgrounds among treatment groups when comparing the seizure-free survival rates., Results: At the 3-year follow-up, seizure-free survival was 15.7%, 32.1%, and 52.4% in the medical, palliative, and resective groups, respectively. The adjusted hazard ratios for seizure recurrence in the resective and palliative groups versus the medical group were 0.43 (95% CI, 0.21-0.87, P=0.019) and 0.82 (95% CI, 0.46-1.46, P=0.50), respectively; the former was statistically significant. Regarding the developmental outcome, the mean DQs in the resective group increased significantly compared to those in the medical group during the follow-up (P<0.01). As for subgroup analysis, better seizure and development outcomes were demonstrated in the resective group compared to the medical group in children with nonsyndromic epilepsies (those to which no known epilepsy syndromes were applicable)., Significance: These results suggest that surgical treatments, particularly resective surgeries, are associated with better seizure and developmental outcomes compared with successive medical treatment. The present observations may facilitate the identification of infants and young children with epileptic encephalopathy who could benefit from surgery., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: We aimed to determine whether different aspects of family functioning are associated with emotional and behavioral problems in adolescents with epilepsy and, if not, to document any indirect associations mediated by other family factors., Methods: This was a cross-sectional, multicenter study. A total of 297 adolescents with epilepsy and their parents participated. Adolescent psychopathology was measured using the Youth Self-Report. Family factors were classified into proximal (parent-child interaction), distal (parent characteristics), and contextual factors (family characteristics) in accordance to their level of proximity to the adolescent's everyday life. Regression analyses were used to analyze the unique and combined predictive power of family factors in relation to psychopathology., Results: In total, 44 (14.8%) and 51 (17.2%) adolescents with epilepsy scored above the borderline cutoff (T-score ≥ 60) of internalizing and externalizing problems, respectively. Proximal and distal factors were independently associated with both internalizing and externalizing problems. High levels of parental depressive mood and parental overcontrol were the strongest factors contributing to internalizing and externalizing problems, respectively. Contextual factors were indirectly associated with both internalizing and externalizing problems through more proximal factors., Conclusions: Both proximal and distal family factors affect psychopathology in Korean adolescents with epilepsy. Parental feelings of depression and parental overcontrol are the strongest factors contributing to internalizing and externalizing problems, respectively., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: There has been little research on whether the knowledge that adolescents with epilepsy (AWE) or their family have about the condition reduces their perception of stigma. In this study we determine the relation between AWE's perceived stigma of, and knowledge about, epilepsy and maternal perception of stigma., Methods: This was a cross-sectional multicenter study involving AWE and their mothers from 25 secondary or tertiary hospitals in Korea. The level of knowledge about epilepsy was assessed using 34 medical items of the Epilepsy Knowledge Profile-General (EKP-M). Additional questionnaires included the Child Stigma Scale, Parent Stigma Scale, and the Maternal Disclosure Management Scale., Results: A total of 243 AWE and their mothers were included. The mean EKP-M score was 20.7 (range, 12-31) for AWE and 22.0 (range, 11-31) for their mothers. AWE and mothers had a neutral perception of stigma on average, but the maternal concealment behavior was high. Multiple linear regression indicated that AWE's knowledge about epilepsy was significantly related to their perception of stigma. Unexpectedly, AWE with a low level of knowledge reported a higher perception of stigma than those with a very low level of knowledge (β=0.280, p=0.040). In addition, higher maternal concealment behavior (β=0.070, p=0.002) and receiving polytherapy (β=0.240, p=0.046) were independent factors predicting higher perception of stigma in AWE., Conclusion: The knowledge that the AWE had about their epilepsy, maternal concealment behavior, and receiving polytherapy were significantly related to the AWE's perception of stigma., (Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to identify the different influencing patterns of demographic and epilepsy-related variables on various aspects of psychosocial function in pediatric epilepsy., Method: Five hundred ninety-eight patients with pediatric epilepsy between the ages of 4 and 18 years (boys=360, 60% and girls=238, 40%) and their parents participated in the study. Parents completed the Social Maturity Scale (SMS), the Korean version of the Child Behavior Checklist (K-CBCL), and the Korean version of the Quality of Life in Childhood Epilepsy Questionnaire (K-QOLCE) to assess daily living function, behavior, and quality of life. The Children's Global Assessment Scale (CGAS) was completed by clinicians to assess general adaptive function. Demographic variables, such as age and sex of child, and epilepsy-related clinical variables, including seizure type, seizure frequency, duration of epilepsy, and number of medications, were obtained from medical records., Results: Demographic and epilepsy-related clinical variables had a strong influence (22-32%) on the cognition-related domain such as general adaptive function, school/total competence, and quality of life for cognitive function while a comparatively smaller effect (2-16%) on the more psychological domain including behavioral, emotional, and social variables. Younger age, shorter duration of illness, and smaller number of medications showed a strong positive impact on psychosocial function in pediatric epilepsy, particularly for adaptive function, competence, and quality-of-life aspects., Conclusion: Given the wide range of impact of demographic and clinical variables on various facets of psychosocial functions, more specific understanding of the various aspects of factors and their particular pattern of influence may enable more effective therapeutic approaches that address both the medical and psychological needs in pediatric epilepsy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Public misconception of epilepsy may lead to significant stigma to the disease itself, thereby causing impaired quality of life in people with epilepsy. Traditionally, epilepsy has been considered to be the consequence of evanescent spiritual forces, and even demonic possession (in many countries). The names of epilepsy in some East Asian countries originated from China, and include madness in their meaning. We recently changed the Korean name of epilepsy, gan-jil (간질, : a crazy, convulsive disease having meaning similar to ), to a neutral and scientifically explainable name: noi-jeon-jeung (뇌전증; ; cerebroelectric disorder). We expect that changing the stigmatized name of epilepsy to a neutral and scientific term with the meaning of cerebroelectric disorder will reduce the social stigma by understanding of epilepsy as one of the neurologic disorders., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Mitochondrial diseases are a group of diseases caused by dysfunctional mitochondria, organelles that generate energy for the cell. Mitochondrial diseases are often caused by mutations, acquired, or inherited in the mitochondrial DNA or nuclear genes that code for respiratory chain complexes in the mitochondrion. Mitochondrial diseases involve multiple organs and show heterogeneous and unpredictable progression. The most common clinical presentation of mitochondrial diseases is encephalomyopathy, and epileptic seizures can frequently occur as a presenting sign of mitochondrial encephalopathy. While whether mitochondrial dysfunction or epilepsy is the cause or consequence is still debatable, they may be interrelated to create a vicious cycle. Epileptic phenotypes vary in different mitochondrial diseases. At present, there are no curative treatments for mitochondrial diseases, and the efficacy of many anticonvulsants, vitamins, nutritional supplements, and the ketogenic diet remain to be proven. Understanding the pathophysiology of mitochondrial diseases may further facilitate effective diagnostic and therapeutic approaches to these diseases., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: We studied children younger than 6years old who developed catastrophic epilepsy and were registered in the FACE study group to clarify their clinical characteristics and prevalence of seizure as well as epilepsy types., Subjects: Subjects were prospectively recruited from children with epilepsy who satisfied the following criteria and underwent intensive examination between 2009 and 2012 in 14 collaborative centers: (1) younger than 6years old and (2) more than 10 seizures/month refractory to all available medical treatments including ACTH therapy, leading to significant psychosocial morbidity., Methods: We analyzed epilepsy onset age, predominant seizure type, etiology, neuropsychological findings, and syndromic classification according to the pre-determined registration format., Results: A total of 314 children were enrolled in this study. Epilepsy onset age in 239 cases (80%) was younger than 12months. The most frequent seizure type was epileptic spasms (ES), followed by generalized tonic seizures (GTS), which accounted for 42% and 20%, respectively. West syndrome (WS) was the most frequent epileptic syndrome and accounted for 37%, followed by unclassified epilepsy at 21%, neocortical epilepsy at 19%, Lennox-Gastaut syndrome at 12%, Dravet syndrome at 4%, Rasmussen syndrome at 2%, and others. The two most frequent causes of epilepsy were cortical dysplasia and chromosomal anomalies, as shown in 16% and 6%, respectively. However, the etiology of nearly one half of all patients remained unknown. Psychomotor development was already worse than a moderate degree in 62% of subjects at the first examination., Conclusion: The highest proportion of catastrophic epilepsy was WS and its related syndromes featuring ES and GTS, followed by neocortical epilepsy, whose psychomotor development was significantly retarded at examinations., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background & Aims: To assess the presence of growth retardation during long-term implementation of ketogenic diet (KD) among children with epilepsy, and verify the presence of catch-up growth in same patients 1 year after diet discontinuation., Methods: Retrospective chart review of 20 males and 20 females was performed and z scores of height, weight and body mass index was obtained at baseline, 2 years into KD, and 1 year after discontinuation of KD., Results: Our analysis revealed significant reduction in both height and weight gain among children with epilepsy after prolonged KD. After a year of diet discontinuation, significant catch-up growth was evident in both height and weight. In regard to specific subsets, ambulation had favorable influence on growth during KD and after diet discontinuation. Uncontrolled epilepsy, and younger age at the start of KD contributed a negative impact on a child's growth., Conclusions: This preliminary observation into long-term growth pattern among recipients of KD will aid both health care providers and patients alike in planning for long-term care extending beyond the duration of dietary treatment., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose: This study was conducted to assess the clinical relevance of diffusion tensor tractography (DTT) in pre- and post-operative evaluations of childhood epilepsy surgery., Materials and Methods: Seventy-two patients who received epilepsy surgery between March 2004 and July 2008 were retrospectively analyzed (M : F=40 : 32, ages of 3 months to 24 years, mean age=8.9 years). DTT was performed using a 3.0 T scanner and single-shot spin-echo echo-planar imaging with 32-different diffusion gradient directions. We reviewed the data focusing on the type of surgery, final pathological diagnosis, and how the DTT data were clinically used., Results: The most common form of childhood epilepsy surgery was complete resection of an epileptogenic lesion (n=52, 72.2%). The reported etiologies included cortical dysplasia (n=32, 44.4%), hippocampal sclerosis (n=9, 12.5%), brain tumors (n=7, 9.7%), and non-pathologic lesions (n=4, 5.6%) in the final diagnoses. Twenty-one dysplastic cortexes and four brain tumors involved an approximal relationship with the corticospinal tract (n=18), optic radiation (n=2), and arcuate fasciculus (n=5). Additionally, although DTT demonstrated white matter tracts clearly, DTT in the hippocampal sclerosis did not provide any additional information. In cases of callosotomy (n=18, 25%), post-operative DTT was utilized for the evaluation of complete resection in all patients. DTT information was not used in functional hemispherectomy (n=2, 2.8%)., Conclusion: Preoperatively, DTT was a useful technique in cases of cortical dysplasia and brain tumors, and in cases with callosotomy, postoperatively. DTT should be included among the routine procedures performed in management of epilepsy.

To retrospectively evaluate the safety and role of ketogenic parenteral nutrition in patients with intractable childhood epilepsy. The ketogenic parenteral nutrition was given to 10 patients who were unable to absorb nutrients through the intestinal tract because of various gastrointestinal disorders and required complete bowel rest. This nutrition consisted of conventional intravenous fat emulsion (20% Lipision) plus dextrose and amino acid (6% Trophamine) hyperalimentation in a 4:1 (or 3:1) lipid to non-lipid ratio, infused during the bowel rest. If the ketogenic parenteral nutrition allowed normal daily functioning or resolved the underlying problems, we soon changed it to the enteral ketogenic diet (KD). The mean (±SD) duration of the ketogenic parenteral nutrition was 4.1 (±1.5) days. Although a brief span of several days, all patients could maintain ketosis and the efficacy of the previous enteral KD during the ketogenic parenteral nutrition. Complications included elevated aspartate aminotransferase and/or alanine aminotransferase in one patient. Amylase and lipase increased in one patient. Serum triglyceride level increased to the level of 1885 mg/dl in one patient, but normalized in one week after discontinuation of the ketogenic parenteral nutrition and resuming of the enteral KD. Nine patients (90%) remained on the enteral KD after the ketogenic parenteral nutrition (the mean follow-up period was 9 months), including 2 patients who successfully completed the diet with seizure free state. Only one patient discontinued the ketogenic parenteral nutrition because of persistent increase of the amylase and lipase levels. The ketogenic parenteral nutrition proved to be a relatively safe short-term method of continuing KD to maintain ketosis for seizure control, while patients were unable to absorb nutrients through their intestinal tract., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: We reviewed retrospectively our experiences with children with intractable epilepsy who were indicated for a modified Atkins diet (MAD)., Methods: Twenty children (8 female, 12 male) who were aged 2-17 years with intractable epilepsy and tried the MAD between September 2008 and December 2010 were enrolled. Outcome measures included seizure frequency, adverse reactions and tolerability of the diet., Results: Finally 9 patients maintained the MAD with favorable seizure outcomes (a reduction of seizure frequency by over 50%) or successfully completed the diet therapy. Two patients who required a long-term trial of the diet therapy respectively due to Leigh's syndrome and uncategorized mitochondrial cytopathy derived from cytochrome c oxidase defect, respectively, successfully maintained the diet treatment without any significant complications. In 7 patients, the ketogenic diet (KD) was not only effective but also too restrictive or caused serious unwanted events. Five of them maintained the seizure outcome previously achieved by the KD with the MAD. Ten patients began the MAD because they were reluctant to start the KD. Unfortunately, only 2 patients maintained the MAD with favorable seizure outcomes. One patient who chose the MAD to bridge the KD and complete discontinuation of the treatment successfully completed the diet therapy., Conclusion: A long-term treatment with the MAD was well tolerated. Moreover, the MAD can successfully substitute the classic KD in patients who showed improvement in seizure outcomes by the KD but could not tolerate it., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

At the 2010 Global Symposium on the Dietary Treatments for Epilepsy and other Disorders held in Edinburgh, there was an opening evening 75-min session to highlight the similarities and differences in the use of the ketogenic diet worldwide. Speakers from seven distinct regions of the world briefly presented their successes as well as challenges in using dietary therapies. Additionally, future clinical and research goals for each area were discussed. This article summarizes these talks and the use of the ketogenic diet worldwide., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose: Rett syndrome is a severe neurodevelopmental disorder in females. Most have mutations in the methyl-CpG-binding protein 2 (MECP2) gene (80-90%). Epilepsy is a significant commonly accompanied feature in Rett syndrome. Our study was aimed at comprehensive analysis of genetic and clinical features in Rett syndrome patients, especially in regards to epileptic features., Materials and Methods: We retrospectively reviewed 20 patients who were diagnosed with MECP2 mutations at Severance Children's Hospital between January 1995 and July 2010. All patients met clinical criteria for Rett syndrome. Evaluations included clinical features, epilepsy classification, electroencephalography analysis, and treatment of seizures., Results: Ages ranged from 3.6 to 14.3 years (7.7±2.6). Fourteen different types of MECP2 mutations were found, including a novel in-frame mutation (1153-1188 del36). Fourteen of these patients (70.0%) had epilepsy, and the average age of seizure onset was 3.0±1.8 years. Epilepsy was diverse, including partial seizure in four patients (28.5%), secondarily generalized seizure in six (42.8%), generalized tonic seizure in two (14.3%), Lennox-Gastaut syndrome in one (7.1%), and myoclonic status in non-progressive encephalopathy in one (7.1%). Motor functions were delayed so that only 10 patients (50.0%) were able to walk independently: five (35.8%) in the epilepsy group and five (83.3%) in the non-epilepsy group. Average developmental scale was 33.5±32.8 in the epilepsy group and 44.4±21.2 in the non-epilepsy group. A clear genotype-phenotype correlation was not found., Conclusion: There is a tendency for more serious motor impairment and cognitive deterioration in Rett syndrome patients with epilepsy.

This study evaluated the effect of topiramate (TPM) on the quality of life (QOL) in childhood epilepsy, using the Korean quality of life in childhood epilepsy (K-QOLCE) questionnaire. An open label, prospective, observational study of the families of 664 children with epilepsy from 41 centers was conducted. The parents completed the K-QOLCE at the baseline visit and again 6months after starting TPM treatment. The parents reported the seizure frequency at both assessment dates. Statistically significant improvements in all K-QOLCE domains except social functioning were found at 6months after starting TPM treatment from the baseline-scores (P<0.05). However, improved QOL scores were not dependent on the reduction in seizure frequency. TPM significantly improved QOL in children with epilepsy, suggesting its potential clinical benefits., (Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the effectiveness of zonisamide (ZNS) as monotherapy in children with newly diagnosed epilepsy., Methods: This randomized, multicenter trial included a 2-4-week titration and a 24-week maintenance phase after randomization to low-(3-4 mg/kg/day) or high-(6-8 mg/kg/day) dose groups as target maintenance dosages. The primary outcome measure was the seizure-free rate over 6 months, while a secondary measure was the change in cognition and behavior from screening to the end of the maintenance phase., Results: Out of 125 patients enrolled, 90 (49 low-dose and 41 high-dose) completed the study. Forty-one patients (63.1%) in the low-dose group and 34(57.6%) in the high-dose group achieved 6 months' freedom from seizures (p=0.66). After treatment, the picture arrangement subtest improved in the low-dose group (p=0.047) while the vocabulary subtest worsened in the high-dose group (p=0.020). Comparing between the two groups, the vocabulary subtest in the high-dose group was significantly worse than that in the low-dose group (p=0.002). Social competence, somatic complaints, depression/anxiety and delinquent and aggressive behavior in the low-dose group were significantly improved (p<0.05). Moreover, total social competence, somatic complaints, delinquent behavior, externalizing, and total behavior problems were significantly more improved in the low-dose group than the high-dose group (p<0.05)., Conclusions: ZNS is an effective monotherapy for newly diagnosed childhood epilepsy. Lower doses of ZNS have a similar efficacy and more beneficial neurocognitive effects compared to higher doses. When prescribing higher doses of ZNS, one must be aware of the possible manifestation of problems associated with language development, such as those affecting vocabulary acquisition., (Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study is to determine the sensibility of each imaging tool in identifying focal cortical dysplasia (FCD) in children and adolescents with epilepsy and to define the prognostic factors of pediatric and adolescent epilepsy surgery., Methods: We identified 48 children with FCD who underwent resective surgery and analyzed their preoperative data. The results of various anatomic and functional neuroimaging studies were compared for accuracy in locating the lesion. We also investigated clinical factors that affected the outcome of surgical treatment., Key Findings: Brain magnetic resonance imaging (MRI) was able to localize FCD in 30 patients and fluorodeoxyglucose positron emission tomography (FDG-PET) and/or subtraction ictal single photon emission computed tomography (SPECT) coregistered with MRI provided additional information that helped to define the lesion in 13 patients. When comparing the pathologic results between a mild malformation of cortical development (MCD) and FCD type I and II, we noted a strong tendency for patients with FCD to have MRI abnormalities (p = 0.005). In addition, severe pathologic features (Palmini's classification, FCD type II) (p = 0.025) showed significant correlation with a better surgical outcome. To define the primary epileptogenic area, various interictal epileptiform discharges and the results of multimodal neuroimaging studies were helpful, and younger age at the time of operation could aid in more favorable surgical outcomes (p = 0.048)., Significance: Our study showed a significant relationship between pathologic grade and the detectability of FCD by brain MRI. In addition, early surgery can be justified by showing that advanced neuroimaging studies in children with FCD and even with extensive epileptiform discharges have a higher rate of success., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

In this paper, we report on a 5-year-old girl who developed a renal stone while following the ketogenic diet to treat refractory seizure disorder. Three months after initiating the ketogenic diet, she developed severe abdominal pain and vomiting. The spot urine calcium-to-creatinine (Ca/Cr) ratio and 24-hour urine evaluation showed hypercalciuria. Computed tomography (CT) imaging revealed a stone in the right ureteropelvic junction, resulting in hydronephrosis of the right kidney. The renal stone disappeared 5 days after conservative treatment; the patient's microscopic hematuria resolved concurrently. In light of this case report, we recommend regularly monitoring the urine Ca/Cr ratio with ultrasonography for further development of renal stones in patients following the ketogenic diet. If these patients exhibit evidence of symptomatic hypercalciuria or cyristalluria, liberalization of fluid restriction and urine alkalization using oral potassium citrate should be considered.

A child's health inevitably affects the parents' psychologic health and quality of life, especially for mothers of disabled children. Caregiver burden and health-related quality of life were investigated in mothers of children with mitochondrial disease, compared with mothers of children with intractable epilepsy. Mothers of children with mitochondrial disease (n = 33) and intractable epilepsy (n = 32) were recruited. The Zarit Burden Inventory, the Medical Outcomes Short Form 36, short version of the World Health Organization Quality of Life, Beck Depression Inventory, and Beck Anxiety Inventory were administered to all participants. Except for duration of illness and number of previous hospitalizations, there was no significant difference in recorded variables between the two groups. Mothers of children with mitochondrial disease had significantly higher caregiver burden and poorer health-related quality of life, particularly related to role limitations, vitality, and mental health. They also had greater levels of depression and anxiety. After adjustment for all covariates, caregiver anxiety was the most important factor affecting overall caregiver burden. With mitochondrial disease, the possibility of maternal inheritance and scarcity of information about the disease might increase anxiety and thus eventually also the caregiver burden. Accurate information about rare diseases provided to caregivers could be helpful in reducing their anxiety., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: This study investigated the efficacy and safety of zonisamide (ZNS) adjunctive therapy in children with intractable epilepsy to existing antiepileptic drugs (AEDs)., Methods: A clinical retrospective study was performed from 2003 to 2005 at two tertiary epilepsy centers. We reviewed the data from 163 children (107 boys and 56 girls) who experienced more than four seizures per month, whose seizures were intractable to an initial 2 or more AEDs, and could be followed up for at least 6months after ZNS adjunctive therapy initiation. Efficacy was estimated by seizure reduction rate according to seizure types including infantile spasms, and adverse events were also measured., Results: Seventy-nine patients (48.5%) out of 163 patients experienced a reduction in seizure frequency of more than 50%, and 25 patients (15.3%) became seizure-free. The rate of seizure reduction greater than 50% in children with partial seizures was 40.5% (17/42) and in children with generalized seizures was 51.2% (62/121). Of 36 patients who manifested mainly myoclonic seizures, 20 patients (55.6%) showed a seizure reduction of more than 50% and 9 patients (25.0%) were seizure-free. Mean maintenance dosage of drug was 8.2mg/kg/day (range 5.0-16.0mg/kg/day). Adverse events were documented in 15 children (9.2%), including somnolence (8 patients), fatigue, and anorexia, but all were transient and successfully managed. One patient discontinued ZNS therapy due to acute pancreatitis., Conclusion: ZNS adjunctive therapy is an effective and safe treatment in various childhood intractable epilepsy.

Ohtahara syndrome (OS) is known as an intractable epileptic syndrome in neonatal and early infantile period, differentiated from early myoclonic encephalopathy (EME) in its etiology. We report a patient with OS associated with mitochondrial respiratory chain complex (MRC) I defect. With ketogenic diet and mitochondrial cocktail therapy, seizures were completely controlled and suppression-burst patterns disappeared 3 months after starting treatment. It is suggested that OS could be caused by specific metabolic disorder such as MRC defect and the intensive therapies including ketogenic diet, vitamin and coenzyme therapy and antioxidant treatment might be helpful for some patients.

To investigate the efficacy and safety of levetiracetam adjunctive therapy in childhood intractable epilepsy, data were reviewed for 130 children who had >or=4 seizures per month, whose seizures were intractable to an initial >or=2 antiepileptic drugs, and who could be monitored for at least 6 months after levetiracetam add-on. Reduction in seizure frequency and related variables were investigated. Sixty-two of the 130 patients (48%) showed a seizure reduction of >or=50%, and 28 patients (22%) became seizure-free. A reduction in seizures by >or=50% was observed in 33/64 in children with partial seizures (52%) and in 29/66 children with generalized seizures (44%). Efficacy did not differ significantly among seizure types. Overall efficacy was unaffected by abnormalities evident from magnetic resonance imaging, by mental retardation, or by maintenance dose of levetiracetam. The mean maintenance dose of levetiracetam was 47.0mg/kg per day (S.D. = +/- 29.7), and mean follow-up duration was 13.4 months (S.D. =+/- 8.7). No demographic features differed significantly between patients with seizure freedom and without seizure remission. Levetiracetam was discontinued in 24 children at last visit (retention rate, 82%). The most common complaint was irritability (5%), and none of the adverse events were life threatening. In conclusion, levetiracetam adjunctive therapy is effective and safe for childhood intractable epilepsy.

Purpose: The aim of this study is to investigate seizure outcomes following epilepsy surgery in non-lesional neocortical pediatric epilepsy., Methods: We performed a retrospective study on 27 patients with intractable childhood epilepsy who received epilepsy surgery between 1999 and 2006 at Sang-gye Paik Hospital and Severance Children's Hospital. None of the patients had any detectable lesions on MRI. Surgical outcome was assessed at least 2 years postoperatively; clinical characteristics, surgical outcome, pathologic findings, types of surgery, localizing features on SPECT, FDG-PET, and long-term video-EEG were reviewed., Results: Eighteen patients (67%) demonstrated an Engel class I outcome postoperatively. The mean follow-up duration was 4.3 years (range, 2.2-9 years). Eighteen out of 27 cases (67%) showed focal localizing features on ictal SPECT, and 21 of 27 cases (78%) showed abnormal findings on PET. Single lobectomy was the most common procedure, and was performed in 20 patients (74%). Multilobar resection was performed in seven patients (26%). Cortical dysplasia was the most common finding during pathological examination, and was observed in 15 (56%) cases. In addition, gliosis was found in two patients (7%) and non-specific pathological findings were described in 10 patients (37%)., Conclusions: In children with intractable epilepsy and a MRI demonstrating no abnormal lesions, epileptic surgery should be strongly considered when cortical pathology can be identified from other studies.

Purpose: We employed the results of imaging modalities from pediatric patients who received successful epilepsy surgery to determine the accuracy of each imaging tool in identifying epileptic zones in youngsters., Methods: All Engel class I pediatric patients who received epilepsy surgery between October 2003 and April 2008 were selected. Their pathology, EEG, MRI, PET, and subtraction ictal SPECT coregistered to MRI (SISCOM) results were compared for accuracy in locating the epileptic foci, defined as "area that resulted in seizure ablation after resection"., Results: Forty-two patients were enrolled (23 temporal lobectomy, 19 extratemporal resections). MRI showed concordance in 84.2% of extratemporal cases, all of which had precise localization of lesions. In temporal cases, lateralization was 91.3% and localization was 82.6%. PET showed a concordance rate of 95.5% and localization was 72.7% for temporal lesions. For extratemporal lesions, concordance was only 68.4%. SISCOM showed concordance in 100% of temporal and 92.3% of extratemporal cases, with localization in 66.7% of temporal and 84.6% of extratemporal cases. Most temporal lobe cases had hippocampal sclerosis, and cortical dysplasia was observed in extratemporal cases., Discussion: MRI was invariably reliable in all cases. PET results were as reliable in lateralizing the temporal epileptic area, while its efficacy was lower for extratemporal cases. SISCOM effectively localized lesions in extratemporal cases, but its efficacy was lower in temporal lesions. In cases of conflicting pre-surgical results, MRI, with supplementary data from PET, helped to establish correct decisions in temporal epilepsies, while utilization of SISCOM and MRI data is advised for extratemporal cases.

This study examines factors influencing the evolution of West syndrome to Lennox-Gastaut syndrome. The study population comprised 98 patients diagnosed with West syndrome and monitored for at least 3 years. During follow-up, West syndrome evolved to Lennox-Gastaut syndrome in 48 of the 98 patients. Etiology analysis indicated that West syndrome was cryptogenic in 36 patients (36.7%) and symptomatic in 62 (63.3%). West syndrome was managed with antiepileptic drugs in 31 patients, ketogenic diets in 33 patients, hormonal therapy with prednisolone in 45 patients and with adrenocorticotropic hormone in 15 patients, epileptic surgery in 3 patients, and either no treatment or only herbal medication in 4 patients. The risk of developing Lennox-Gastaut syndrome was significantly lower in patients who were placed on a ketogenic diet, given prednisolone or adrenocorticotropic hormone, or treated with a combination of these two therapies (bivariate logistic regression analysis, P < 0.05). There was no relationship between the development of Lennox-Gastaut syndrome and age at West syndrome onset or disease etiology. In conclusion, a ketogenic diet and hormonal therapy may play key roles in preventing encephalopathy in patients with West syndrome.

Objectives: The unfavorable surgical results that have been reported with insular epilepsy surgery may be related to inadequate monitoring. Insular epilepsy surgery requires the precise monitoring and tailored removal of the epileptic zone. The purposes of this study were to precisely monitor the hidden cortex and determine the effectiveness of using different monitoring methods, including subpial depth electrodes., Materials and Methods: This is a study of a single center series of six patients (three men, three women) who underwent insular surgery between May 2006 and December 2007. All patients had experienced medically intractable seizures without any evidence of a tumorous condition based on previous examination. We used strip electrode implantation in one patient and stereotactic depth electrode insertion in two patients, which resulted in partial removal of the insular. The other three patients underwent open direct subpial depth electrode insertion, which resulted in total removal of the insular cortex., Results: There were no surgery-related complications with the insulectomy after insertion of the subpial depth electrodes, regardless of the monitoring method or extent of removal. All patients except for one showed considerable improvement in epilepsy (83.3% Engle class I, 16.5% Engle class II). In the three patients who had open direct subpial depth electrodes inserted, we achieved total insulectomy without increasing the surgical morbidity, while in the other three patients, the insular removal was only partial., Conclusion: We demonstrate that image-guided insular surgery with safe and accurate depth electrode guidance results in an optimal outcome and complete resection of the insular cortex.

Epilepsy from hamartoma of the floor of fourth ventricle (HFFV) is very rare, starting in neonate or infantile period, good response to surgery. We report a 3-month-old boy with episodes of medically intractable abnormal eyelid blinking and hemifacial seizure. The episodes began from the first day of life and were unresponsive to medication. A magnetic resonance imaging scan revealed mass lesion on the floor of fourth ventricle, with extended cerebellar peduncle and cerebellar hemisphere. Surgery had been performed two times previously for treatment; only a subtotal resection was performed due to severe bradycardia during the first operation. The patient underwent second operation for gross total removal of tumor. Complete resection of the mass after second surgery resulted in remission of seizures and histopathology revealed hamartoma with hemangiomatous vessel proliferation. Identification of characteristic semiology and associated HFFV can help prediction of intractability even in infant and favoring surgical treatment in early age. To our knowledge, this is the youngest patient who underwent early surgery just after progressing into status for HFFV, showing complete lesion resection resulting in successful seizure outcome.

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research.

The ketogenic diet (KD) is a high fat, low carbohydrate diet that has been used for intractable childhood epilepsy since the early 1920s. After the resurgence of the KD since the mid 1990s in the United States, there has been a dramatic increase in its use worldwide. The increasing use of this diet in Asia is not an exception. However, since carbohydrates are considered to be a main dietary composition of Asians, there has been some limitation on the rapid adaptation of KD. This summary will give a brief review on current state, limitations, and efforts to provide a successful KD in Asia.

We sought to determine the cause of gastrointestinal (GI) intolerance of a ketogenic diet (KD) using an endoscopic investigation, and to examine the relationship between endoscopic lesions and dietary tolerance. Thirty-five patients were enrolled in this study and underwent gastrofiberscopy prior to initiation of the KD. We observed the relationship between abnormal endoscopic findings and prior use of antiepileptic drugs (AEDs) and symptoms of GI disturbance. We treated patients with GI symptoms, and observed whether the KD was subsequently better tolerated. Of the 35 patients enrolled, 20 patients (57%) had abnormal endoscopic findings: ten cases of erosive gastritis, four of duodenitis, three of hemorrhagic gastritis, two of esophagitis, and one case of duodenal ulcer. The incidence of abnormal endoscopic lesions was 78% in the polypharmacy group (14/35) and 81% in steroid consumers (16/35). Symptoms of GI disturbance, such as nausea, vomiting, unusual irritability, cramping abdominal pain, and diet refusal for over a day, were observed in 17 (85%) of those patients with abnormal endoscopic lesions and in five (33%) patients without such lesions. Steroids and polypharmacy with more than three AEDs were factors associated with abnormal endoscopic lesions (p < 0.05). After active management with GI medications, GI symptoms subsided, and in all cases except one, patients were able to continue the KD treatment. In conclusion, symptoms of GI disturbance were frequently associated with abnormal endoscopic findings prior to initiation of the KD. Active management with GI medications increased the tolerability of the KD in patients treated with multiple AEDs and steroids.

Purpose: To evaluate the efficacy and safety of zonisamide (ZNS) as long-term adjunctive therapy in children with Lennox-Gastaut syndrome (LGS)., Method: We evaluated the seizure frequency, cognitive outcomes, and side effects of 62 LGS patients maintained on ZNS for at least 12 months in three tertiary centers., Results: Of the 62 LGS patients maintained on ZNS, 3 (4.8%) had 100% seizure control; 14 (22.6%) had >75% to <100% reduction in seizure frequency; 15 (24.2%) had >50% to <75% reduction in seizure frequency; 6 (9.7%) had >0% to <50% reduction in seizure frequency, and 24 (38.7%) had no seizure reduction. Seizure outcomes were not related to seizure types or etiologies. Adverse events included somnolence and anorexia, but all were transient and successfully managed by careful follow-up., Conclusion: Our results indicate that adjunctive treatment with ZNS is safe and effective in pediatric LGS patients.

Objective: Hypothalamic hamartomas (HHs) are often associated with early-onset gelastic seizures, thus configuring a well recognized and usually severe case of childhood epilepsy syndrome. We present a treatment modality for intractable epilepsy in hypothalamic hamartomatous lesions., Methods: This study presents 14 patients with medically refractory seizure associated with HHs treated between 1995 and 2005. The HHs were diagnosed on the basis of magnetic resonance imaging, except in the case of one patient in whom hamartoma was confirmed histologically. There were seven boys and seven girls in this study. The most frequent clinical presentations were seizures. To identify the epileptic focus, we performed comprehensive epilepsy investigations, including electroencephalographic recording using a depth electrode into the hamartoma., Results: To control the seizure, we performed surgical resection in one patient, gamma knife radiosurgery in four patients, and endoscopic disconnection in 11 patients. Seizure outcome was scored according to Engel's classification throughout a mean follow-up period of 27.4 months (range, 3-54 mo). Of the 11 patients who underwent endoscopic disconnection, six were seizure-free immediately after surgery. Two patients were already diagnosed as having an HH and underwent gamma knife radiosurgery, but seizure control was not achieved. Their gelastic seizure disappeared after endoscopic disconnection., Conclusion: We confirmed that HHs are intrinsically epileptogenic. Therefore, we suggest that HH-related seizures may be controlled by blocking the seizure propagation from epileptogenic HHs through simple disconnection, regardless of the treatment modality, and the endoscopic disconnection of HHs is safer and more effective than other modalities.

Purpose: To determine if defects in mitochondrial respiratory chain enzyme complexes (MRCs) contribute to the etiology of childhood epilepsy., Methods: We reviewed the clinical and laboratory features of 48 epileptic patients (23 male, 25 female) with MRC defects that were confirmed by biochemical assays using muscle biopsies., Results: (1) Thirty-five cases (72.9%) were MRC I deficient, one case (2.1%) was MRC II deficient, 11 cases (22.9%) were MRC IV deficient, and one case (2.1%) had combined MRC I and IV deficiencies. (2) In our clinical diagnosis, there were 10 cases (20.8%) with Leigh disease and one case each with myopathy, encephalopathy, lactic acidosis, stroke-like episodes (MELAS) or Alpers' disease (2.1%). Most of the remaining cases (75.0%) had uncategorized mitochondrial cytopathy with nonspecific encephalopathy. (3) For epileptic classification, there were two cases (4.2%) of Ohtahara syndrome, 10 cases (20.8%) of West syndrome, 12 cases (25.0%) of Lennox-Gastaut syndrome, two cases (4.2%) of Landau-Kleffner syndrome, 14 cases (29.2%) of generalized epilepsy, and eight cases (16.7%) of partial epilepsy. (4) The mean age of seizure onset was 2.68 +/- 2.21 (range: 1 month - 5.5 years). (5) Magnetic resonance imaging (MRI) showed diffuse cortical atrophy in 34 cases (70.8%), basal ganglia signal changes in 18 cases (37.5%) and thalamus signal changes in 12 cases (25.0%). (6) A ketogenic diet produced clinical improvements, including seizure reduction and global functional improvement in 75% of 24 patients., Conclusions: MRC defects are one of the important causes of probably symptomatic childhood epilepsy. A ketogenic diet should be carefully considered for treatment of intractable epilepsy related to MRC defects.

Purpose: To compare the efficacy of corpus callosotomy and vagus nerve stimulation (VNS) for long-term adjunctive therapy in children with Lennox-Gastaut syndrome (LGS)., Method: Fourteen patients underwent a total corpus callosotomy and 10 patients received VNS implantation. The patients were monitored for more than 12 months after treatment, and seizure rates and complications were retrospectively evaluated., Results: Seizure types among the 24 patients included atonic or tonic seizures with head-drops in 17 patients, generalized tonic seizures in two patients, atypical absence seizures in one patient, generalized tonic-clonic seizures in one patient, and myoclonic seizures in three patients. Of the 14 patients who underwent a corpus callosotomy, nine (64.3%) had a greater than 50% reduction in seizure frequency and five (35.7%) had a greater than 75% reduction. Of the 10 patients who underwent VNS implantation, seven (70.0%) had a greater than 50% reduction in seizure frequency and two (20.0%) had a greater than 75% reduction. There was no significant difference between the two procedures in terms of final efficacy. Complications of corpus callosotomy included aphasia in one patient, ataxia in another, and paresis in a third. Among patients receiving VNS, one patient experienced dyspnea while sleeping and one patient suffered from drooling. These complications were transient and tolerable, and were controlled by simple adjustments of VNS treatment parameters., Conclusion: The efficacy and safety of corpus callosotomy and VNS were comparable in children with LGS.

Objectives: This study sought to characterize epileptic phenotypes in children with nonspecific mitochondrial disease (MD) and to evaluate MD diagnostic approaches., Methods: A retrospective analysis of the medical, electroencephalogram, and laboratory records of 142 patients with epilepsy was performed. The patients were evaluated for MD, and 124 patients were included in the final cohort. The MD criteria used included an oral glucose lactate stimulation test (OGLST) and urine organic acid/plasma amino acid (UOA/PAA) assays as metabolic indicators of modified Walker criteria, as suggested by Bernier et al. (Neurology 59:1406-1411, 2002)., Results: Twenty-two patients were classified as having definite MD (9), probable MD (5), possible MD (6), or pyruvate dehydrogenase (PDH) deficiency (3), including one patient which showed a respiratory chain (RC) defect and PDH deficiency. Seven out of eight patients in whom significant RC defects were observed showed complex I defects. In 14 patients, epileptic seizures start at infantile ages. Of 17 patients who substantially presented generalized seizures, 4 patients started with partial seizures. Five patients consistently presented only partial seizures. The OGLST and UOA/PAA assays were useful for a more precise diagnosis of MD, although low positive predictive value of the OGLST was regrettable. No patient was classified as definite MD by Walker's original criteria, but the use of our revised MD criteria resulted in the classification of nine additional patients as definite MD., Conclusions: MD manifested considerable diverse epileptic phenotypes and should be considered in the differential diagnosis of epilepsy in children with unexplained encephalomyopathy and progressive and fluctuating clinical courses.

We evaluated the long-term outcome of vagus nerve stimulation (VNS) in 28 children with refractory epilepsy. Of these 28 children, 15 (53.6%) showed a >50% reduction in seizure frequency and 9 (32.1%) had a >75% reduction. When we compared seizure reduction rates according to seizure types (generalized vs. partial) and etiologies (symptomatic vs. cryptogenic), we found no significant differences. In addition, there was no correlation between the length of the stimulation period and treatment effect. The seizure reduction rate, however, tended to be inversely related to the seizure duration before VNS implantation and age at the time of VNS therapy. VNS also improved quality of life in this group of patients, including improved memory in 9 (32.1%), improved mood in 12 (42.9%), improved behavior in 11 (39.3%), improved alertness in 12 (42.9%), improved achievement in 6 (21.4%), and improved verbal skills in 8 (28.6%). Adverse events included hoarseness in 7 patients, dyspnea at sleep in 2 patients, and wound infection in 1 patient, but all were transient and successfully managed by careful follow-up and adjustment of parameters. These results indicate that VNS is a safe and effective alternative therapy for pediatric refractory epilepsy, without significant adverse events.

Purpose: The ketogenic diet (KD) has been considered a highly potent antiepileptic treatment for intractable childhood epilepsy. In this study, we compared the antiepileptic efficacy and diet tolerability of two different diets with lipid:nonlipid ratios of 3:1 and 4:1., Methods: Seventy-six patients with refractory childhood epilepsy were randomly placed into two groups and were started on KD diets with nonlipid:lipid ratios of either 3:1 or 4:1. Antiepileptic efficacy and diet tolerability were evaluated 3 months after initiating the diet. Patients showing seizure-free outcome with the 4:1 diet were changed to the 3:1 diet, and those without a seizure-free outcome on the 3:1 diet were changed to the 4:1 diet, for three more months, after which time their progress was monitored., Results: (1) Antiepileptic efficacy was higher for the 4:1 than the 3:1 diet (p < 0.05). Twenty-two (55.0%) of 40 patients on the 4:1 diet and 11 (30.5%) of 36 patients on the 3:1 diet became seizure free. Seizure reduction of over 90% was observed in 2 (5.0%) patients on the 4:1 diet, and 2 (5.6%) on the 3:1 diet. (2) Dietary tolerability was better for the 3:1 than the 4:1 diet. Gastrointestinal symptoms were observed in 5 (13.9%) patients with the 3:1 diet and 14 (35.0%) patients with the 4:1 diet (p < 0.05). (3) For seizure-free patients who started on the 4:1 diet, antiepileptic efficacy was maintained after changing to the 3:1 diet, while 10 (83.3%) of 12 patients who were not seizure free with the 3:1 diet showed increased seizure reduction after changing to the 4:1 diet. (4) Complications from the KD and laboratory data were not significantly different between the two groups., Conclusions: The 4:1 KD showed greater antiepileptic efficacy than the 3:1 diet with higher seizure-free outcome. In most cases, seizure free outcome was maintained even after changing the ratio to 3:1. Dietary tolerability was better in the 3:1 diet than the 4:1 with less frequent gastrointestinal symptoms.

Purpose: To evaluate the efficacy, safety and tolerability of a modified Atkins diet in intractable childhood epilepsy., Methods: Fourteen children with epilepsy were treated prospectively with a modified Atkins diet. Outcome measures included seizure frequency, adverse reactions and tolerability to the diet; blood beta-hydroxybutyrate and urine ketones were also measured., Results: Six months after diet initiation, seven (50%) remained on the diet, five (36%) had >50% seizure reduction, and three (21%) were seizure free. The diet was well tolerated by 12 (86%) patients. Most complications were transient and were successfully managed by careful follow-up and conservative strategies. A consistently strong ketosis (beta-hydroxybutyrate of >3 mmol/L) seemed to be important for maintaining the efficacy of the diet therapy., Conclusions: The modified Atkins diet was well tolerated and sometimes a modified Atkins diet can be substituted for the conventional ketogenic diet. Serious complications were rare, but long-term complications remain to be determined.