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Aims: We aimed to delineate the phenotypic spectrum of SCN2A-related developmental and epileptic encephalopathy (DEE) and determine the effectiveness of various treatment modalities, including sodium channel blockers and the ketogenic diet., Methods: Eleven patients with SCN2A-related DEE were included in the study. The characteristics of SCN2A mutations, electroclinical features, clinical course, and response to treatment modalities were analysed., Results: The 11 patients were aged between 0.4 and 9.7 years. The onset of seizures ranged from neonate (six patients) to infant (four patients), to childhood (one patient). Epilepsy presented as Ohtahara syndrome, West syndrome, epilepsy of infancy with migrating focal seizures (EIMFS), and focal epilepsy in neonatal- to infantile-onset patients. The only childhood-onset patient in our study presented with focal epilepsy with autism. Neonatal-to infantile-onset patients had drug-resistant epilepsy (9/10), however, sodium channel blockers were effective in all treated patients (9/9). The ketogenic diet (6/8) and high-dose steroid treatment (4/5) were also effective. The seizures in the childhood-onset patient worsened during treatment with sodium channel blockers. All mutations in neonatal- to infantile-onset patients were missense mutations, whereas the mutation in the childhood-onset patient was a truncation mutation., Conclusions: These results support earlier observations regarding the epilepsy syndromes and response to antiepileptic drugs in patients with SCN2A-related DEE.

Infantile spasms constitute a catastrophic epileptic condition. Seizures in approximately half of children with infantile spasms fail to improve with initial treatment attempts; at present, data regarding alternative treatments are limited. We assessed the efficacy of clobazam as an adjunctive therapy in patients whose seizures failed to respond to initial regimens of standard treatment for infantile spasms. All patients from Severance Children's Hospital who received clobazam as adjunctive therapy for infantile spasms were selected for the study. The efficacy of clobazam was evaluated by assessing the daily spasm frequency. Patients were categorized as complete responders if the spasms disappeared within 2 weeks of introducing clobazam, and the patients became spasm-free during weeks 3 and 4. Tolerability was gauged by analyzing adverse events and discontinuation rates. In all, 171 patients qualified for the analysis. Clobazam was introduced after the administration of 2.6 (median; interquartile range [IQR], 1.0-4.0) failed antiepileptic drugs (AEDs), at the age of 8.2 months (IQR, 6.0-10.0 months). After clobazam therapy was initiated, 38 (22.2%) patients became spasm-free for ≥2 weeks. Thirteen out of the 38 complete responders remained spasm-free until the last follow-up and did not require the administration of other AEDs. In 10 patients, the electroencephalogram (EEG) tracings were also within normal limits. These patients were successfully weaned off of all AEDs. Patients with conditions of unknown etiology, who had fewer prior exposures to AEDs, and had not received prior adrenocorticotropic hormone (ACTH)/steroids were more likely to have complete spasm control than the others. Adverse effects were minor, and only 6 of 101 (6%) patients who experienced adverse events had their treatments discontinued during the 3-month follow-up period. The most common adverse events observed were hypersalivation, sedation, and sleep disturbance. Thus, clobazam might be an effective and safe alternative therapeutic option in patients whose seizures failed to respond to initial regimens of standard treatment for infantile spasms. Further prospective studies on clobazam for infantile spasms, focusing on specific good response groups, dosing protocols, and long-term outcome are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The treatment options for Lennox-Gastaut syndrome (LGS), a pediatric epileptic syndrome, are limited, especially in younger children. Rufinamide tablets were safe and effective as an add-on treatment in Korean children and adolescents <20 years of age with LGS. This subgroup analysis aimed to evaluate the efficacy and safety of rufinamide tablets in LGS pediatric patients aged 1-4 years., Methods: This was a retrospective, observational study in LGS patients aged 1-4 years who received 12 weeks of treatment with rufinamide orally as an adjuvant treatment between April and June 2010. The proportion of responders (patients with a ≥50% reduction in seizure frequency after rufinamide treatment) was evaluated according to the type of seizure. The proportion of patients who were seizure-free was also evaluated. Adverse events (AEs) were evaluated after 12 weeks of treatment., Results: Among the 15 patients evaluated, one discontinued treatment because of worsening seizures 4 weeks after administration of rufinamide. Seven (46.67%) patients were responders and four patients were seizure-free. There were four responders with convulsive seizures, one each for myoclonic seizures and drop attacks, and spasms. The responder rate was increased to 69.23% by long-term treatment of rufinamide. AEs were experienced by three patients. One patient each experienced somnolence, fatigue, and rash., Conclusion: Rufinamide tablets were efficacious and well tolerated in LGS patients aged 1-4 years, at doses up to 1000 mg per day, when given as add-on therapy to other antiepileptic drugs., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: Hormonal therapy and vigabatrin are now accepted as the first-line or standard therapies for West syndrome (WS). However, the superiority of these drugs in terms of monotherapy or combination therapy is still in question. In this study, we designed a treatment protocol for WS and prospectively assessed the efficacy of these therapies in controlling spasms, stabilizing electroencephalography (EEG), and allowing for developmental catch-up., Methods: In patients diagnosed with WS, vigabatrin was first administered alone for 2 weeks, and then prednisolone was administered in combination with vigabatrin if patients did not respond to vigabatrin. The detailed drug administration protocol was as follows: vigabatrin 50 mg/kg/day for 1 day, followed by vigabatrin 100 mg/kg/day for 3 days, vigabatrin 150 mg/kg/day if spasms were still present or the burden of amplitudes and epileptiform discharges (BASED) score on EEG was ≥3 on day 5; 40 mg/day of prednisolone was added if spasms were still present or the BASED score was ≥3 on day 14. The prednisolone dose was increased to 60 mg/day if spasms were still present or the BASED score was ≥3 on day 21., Results: Sixty-six patients newly diagnosed with WS (median seizure onset age: 5.7 [IQR, 4.1-7.1] months, median age at diagnosis: 6.6 [IQR, 5.4-8.1] months, n = 40 [60.6%] boys) were subjected to the vigabatrin and prednisolone therapy protocol. Of the 66 patients, 22 (33.3%) patients showed resolution of spasms and a BASED score of ≤2 after vigabatrin alone, and 26 (39.4%) patients showed resolution of spasms and a BASED score of ≤2 after a combination of vigabatrin and prednisolone, for a total of 48 (72.7%) patients who were responsive to the protocol without relapse for at least 7 months after WS diagnosis. The mental and psychomotor age quotients were higher at the time of diagnosis and remained significantly higher 6 months after the diagnosis in responsive patients (p <  0.001). No serious adverse reactions leading to discontinuation or reduction of drug doses were observed., Conclusion: Using a treatment protocol involving vigabatrin and prednisolone for WS, 72.7% of patients showed resolution of spasms and a BASED score of ≤2. This study also found that this drug administration protocol was safe. However, further studies are warranted as this study describes results from observational study with limited sample size., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To prospectively evaluate the neuropsychological effect of levetiracetam (LVT) in comparison with carbamazepine (CBZ) and its efficacy and tolerability as a monotherapy in children with focal epilepsy., Methods: A total of 121 out of 135 screened children (4-16 years) were randomly assigned to LVT or CBZ groups in a multicenter, parallel-group, open-label trial. The study's primary endpoints were defined as the end of 52 weeks of treatment, followed by analysis of changes observed in a series of follow-up neurocognitive, behavioral, and emotional function tests performed during treatment in the per protocol population. Drug efficacy and tolerability were also analyzed among the intention-to-treat (ITT) population (ClinicalTrials.gov, number NCT02208492)., Results: Eighty-one patients (41 LVT, 40 CBZ) from the randomly assigned ITT population of 121 children (57 LVT, 64 CBZ) were followed up to their last visit. No significant worsening or differences were noted between groups in neuropsychological tests, except for the Children's Depression Inventory (LVT -1.97 vs CBZ +1.43, p = 0.027, [+] improvement of function). LVT-treated patients showed an improvement (p = 0.004) in internalizing behavioral problems on the Korean Child Behavior Checklist. Seizure-free outcomes were not different between the 2 groups (CBZ 57.8% vs LVT 66.7%, p = 0.317)., Conclusions: Neither LVT nor CBZ adversely affected neuropsychological function in pediatric patients. Both medications were considered equally safe and effective as monotherapy in children with focal epilepsy., Classification of Evidence: This study provides Class II evidence that in patients with pediatric focal epilepsy, LVT and CBZ exhibit equivalent effects on neuropsychological function., (© 2015 American Academy of Neurology.)

Background: Our aim was to investigate the efficacy and tolerability of levetiracetam as an add-on treatment in pediatric patients with Lennox-Gastaut syndrome., Methods: The study was an open-label, multicenter, observational clinical trial of levetiracetam as an add-on treatment in Lennox-Gastaut syndrome. Fifty-five patients aged 1.1-18.6 years (mean, 10.0 years) were enrolled. The study included a 4-8-week titration period and an 8-week maintenance period. The maintenance dose of levetiracetam was 20-80 mg/kg/day, according to its effectiveness and tolerability. The primary end point was reduction in seizure frequency, and related variables were also evaluated., Results: Among 55 patents, 51 patients (92.7%) completed the study. Thirty-two patients (58.2%) experienced a more than 50% reduction in seizure frequency, and 15 patients (27.3%) became seizure free. A reduction in seizure frequency of more than 50% was observed in 21 of 36 patients (58.3%) with convulsive seizures, 7 of 12 patients (58.3%) with drop attacks, 2 of 4 patients (50.0%) with myoclonic seizures, and 2 of 3 patients (66.7%) with epileptic spasms. Overall, 34.5% of patients reported adverse events. None of the adverse events were life threatening, and the most common adverse event was hyperactivity (12.7%)., Conclusions: This study suggests that levetiracetam is a safe and effective treatment in pediatric patients with Lennox-Gastaut syndrome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To compare the cognitive and behavioral effects of lamotrigine (LTG) to carbamazepine (CBZ) as monotherapy for pediatric epilepsy. A multicenter, randomized, open-label, parallel-group clinical trial was conducted in children with partial-onset seizures. LTG or CBZ was prescribed as monotherapy for previously untreated children and titrated over 8 weeks, followed by maintenance for 24 weeks. Outcome measures were change in cognition and behavior in a combined analysis of standardized measures from screening to the end of the maintenance phase, as well as antiepileptic efficacy and tolerability. A total of 67 children completed the study, including 32 of 43 (74.4%) treated with LTG and 35 of 41 (85.4%) treated with CBZ. Seizure-free outcomes did not differ between the intent-to-treat populations (53.5% LTG, 56.1% CBZ; p=0.81). There were no statistically significant differences in the intelligence of the two groups after treatment. Externalizing behavior problems improved in the CBZ group (p<0.05). However, there were no significant differences between the two groups in terms of externalizing behavior. The parents' report on the Conner scale showed an improvement in the CBZ group compared to the LTG group (p<0.05). LTG and CBZ showed similar efficacy and cognitive effects in treating childhood partial epilepsy. However, CBZ showed more benefits in improving externalizing behaviors., (Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the efficacy of rufinamide as an add-on treatment in children and adolescents with Lennox-Gastaut syndrome (LGS)., Methods: The study was an open-label, observational clinical trial of rufinamide as an add-on treatment in intractable LGS patients. This intent-to-treat trial included 4 weeks of scheduled titrated doses and a 12-week maintenance phase with a target dose of 20-40 mg/kg rufinamide, adjusted according to its effectiveness and tolerability after a baseline period of 4 weeks. The primary outcome was measured by the seizure-reduction rate according to individual seizure type over the 12-week maintenance period., Results: One hundred and twenty-eight patients with LGS who were determined to be unresponsive to one or more antiepileptic drugs or dietary therapy were enrolled. Of the 128 patients enrolled, 112 (87.5%) completed the study. After add-on rufinamide treatment, 46 patients (35.9%) achieved a more than 50% reduction in seizure frequency and 10 (7.8%) patients became seizure-free. When we identified those who responded with an at least 50% reduction in seizure frequency, 39.4% of the responders reported reductions in convulsive seizures, 36.4% in drop attacks, 33.3% in myoclonic seizures, and 20.0% in epileptic spasms. Overall, 32.8% of patients reported adverse effects, which were mostly mild and transient in nature. The most common adverse effects were fatigue (15 patients, 11.7%) and poor appetite (9 patients, 7.0%). Twenty-one (16.4%) patients experienced an increased seizure frequency., Conclusions: Rufinamide appears to be a safe and effective adjuvant treatment for many cases of intractable LGS., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

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: 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.

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.

Purpose: This study examined the characteristics and outcomes of resective epilepsy surgery following corpus callosotomy (CC) in children with Lennox-Gastaut syndrome (LGS). Methods: We retrospectively analyzed 17 children with LGS who underwent resective surgery (RS) after CC over a span of 10 years, with a minimum of 2 years of follow-up, at a single tertiary epilepsy center in Korea. Results: Of the 17 patients, 13 (73.5%) demonstrated favorable surgical outcomes (Engel class I or II) at 1 year after RS, and eight (47.1%) were ultimately free of seizures 2 years after surgery. A significantly larger decrease in the number of anti-seizure medications taken from before to 2 years after the final surgical procedure was observed in the group that became seizure-free than in the group with persistent seizures (P=0.062). Furthermore, a significantly greater decline in daily adaptive function was found in the persistent seizure group (P=0.059). The baseline characteristics, results of presurgical evaluation, and treatment-related factors assessed prior to surgery showed no significant differences between the seizure-free group and the group with persistent seizures. Conclusion: In conclusion, RS may be a viable option for patients with LGS who exhibit lateralization and/or localization on presurgical evaluation after CC, as the procedure may reveal a concealed primary focus. The proactive implementation of two-stage epilepsy surgery could provide significant seizure reduction and preservation of cognitive function in carefully selected patients with LGS. [ABSTRACT FROM AUTHOR]

Purpose: Lamotrigine (LTG) is often used as adjunctive therapy in Lennox-Gastaut syndrome (LGS); however, it may worsen myoclonic and atypical absence seizures in LGS patients. This study reviewed the overall efficacy and safety of LTG in children with LGS. Methods: This retrospective study included 38 patients (aged <18 years) with LGS who underwent LTG adjunctive therapy between October 2020 and March 2022 at Severance Children's Hospital. The primary outcome was the change in seizure frequency at 3, 6, and 12 months after starting LTG treatment. A favorable treatment response was defined as a ≥50% reduction in seizure frequency. Results: The main seizure semiology at the start of treatment was tonic-clonic in 15 (39.5%) patients, spasm in 14 (36.8%), atonic in five (13.2%), myoclonic in three (7.9%), and absence in one (2.6%). The median number of anti-seizure medications (ASMs) was 3.95 (interquartile range, 3 to 4.75). The most common concomitant ASMs were valproate (35/38, 92.1%), levetiracetam (23/38, 60.5%), and topiramate (20/38, 52.6%). After 3 months, seizure frequency was reduced by >50% in 47.4% of patients (18/38). After 6 months, 20 patients (20/36, 55.6%) showed a favorable response. After 12 months, five patients (5/11, 45.5%) responded to treatment. Three patients showed myoclonic seizures at the start of treatment and >50% amelioration in seizure frequency at the 3- and 6-month follow-up visits. Conclusion: This study reaffirms the efficacy and safety of LTG in children with LGS. Therefore, LTG is strongly recommended as an adjunctive therapy for children with LGS. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess the efficacy and safety of lacosamide in Korean adolescents with Lennox-Gastaut syndrome (LGS), especially in those who concomitantly used other sodium channel blockers (SCBs). Methods: We retrospectively reviewed the medical records of adolescents with LGS who initiated lacosamide from ages 16 to 18. The efficacy of lacosamide was evaluated by seizure frequency before and after lacosamide trial. Safety was assessed by lacosamide-related adverse events, consequent dosage titration, and titration effects. We compared the efficacy and safety of lacosamide according to concomitant use of other SCBs. Results: In 26 eligible adolescents with LGS, the median age of seizure onset was 2.0 years, and the median age of lacosamide initiation was 17.1 years. At the time of lacosamide initiation, the median number of concomitant antiepileptic drugs was 4, and 23 patients (88%) had tried dietary, surgical, or neuromodulatory therapies. Patients were on lacosamide for a median of 13.5 months with a median maximal dosage of 8.1 kg/mg/day. After lacosamide trial, 11 patients (42%) had an over 50% reduction of seizures. Six patients (23%) had lacosamide-related adverse events. The percentage of patients on concomitant SCBs was higher among non-responders (10 of 15, 67%) than among responders (6 of 11, 55%). Patients taking concomitant SCBs had a higher ratio of adverse effects (5 of 16, 31%) than their counterparts (1 of 10, 10%). Conclusion: Lacosamide is an effective and tolerable antiepileptic drug in adolescents with LGS. Concomitant SCB use may lead to less effective treatment and more adverse events. [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]

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. [Copyright &y& Elsevier]

Hormone therapies and vigabatrin are first-line agents in infantile spasms, but more than one-third of patients fail to respond to these treatments. This was a retrospective study of patients with infantile spasms who were treated between January 2005 and December 2017. We analyzed the response rates of initial treatment and second-line treatment. Responders were defined as those in whom cessation of spasms was observed for a period of at least one month, within 2 weeks of treatment initiation. Regarding the response rate to initial treatment, combination therapy of vigabatrin with prednisolone showed a significantly better response than that of vigabatrin monotherapy (55.3% vs. 39.1%, p = 0.037). Many drugs, such as clobazam, topiramate, and levetiracetam, were used as second-line agents after the failure of vigabatrin. Among these, no antiepileptic drug showed as good a response as prednisolone. For patients who used prednisolone, the proportion of responders was significantly higher in the higher-dose group (≥40 mg/day) than in the lower-dose group (66.7% vs. 12.5%, p = 0.028). Further studies of combination therapy to assess dosage protocols and long-term outcomes are needed. [ABSTRACT FROM AUTHOR]

Abstract: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet with an established efficacy for treating medically refractory epilepsy in children. Fatty acids are the most important constituent of the KD in all aspects of efficacy and complications. Among fatty acids, polyunsaturated fatty acids (PUFAs) increase anticonvulsant properties and reduce the complications associated with the high-fat diet. Here, we report a 7-year-old boy with Lennox–Gastaut syndrome combined with mitochondrial respiratory chain complex I deficiency, whose medically intractable seizures have been successfully controlled with a PUFA-enriched modified Atkins diet without any significant adverse events. The diet consists of canola oil and diverse menu items like fish and nuts instead of olive oil and has an ideal 1:2.8 ratio of omega-3 to omega-6. In addition, fractionation of this boy’s plasma showed normal levels of fatty acids, including omega-3 (alpha-linoleic acid, eicosapentaenoic acid) and omega-6 (linoleic acid, arachidonic acid) as well as monounsaturated fatty acids (oleic acid). Plasma docosahexanoic acid remained low after PUFA-enriched diet therapy. PUFA-enriched diet therapy is likely to increase the efficacy of diet therapy and reduce complications of a high-fat diet in children with refractory epilepsy. [Copyright &y& Elsevier]

To investigate the efficacy and safety of levetiracetam adjunctive therapy in childhood intractable epilepsy, data were reviewed for 130 children who had ≥4 seizures per month, whose seizures were intractable to an initial ≥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 ≥50%, and 28 patients (22%) became seizure-free. A reduction in seizures by ≥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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: to evaluate the outcomes and role of epilepsy surgery in children with intractable epileptic encephalopathy (EE). Methods: ninety-five children (64 boys, 31 girls) with intractable EE were treated by epilepsy surgery at Severance Children’s Hospital from 2003 to 2008. Surgical treatments included lobar resection, hemispherotomy and corpus callosotomy (CC). Seventy-six children were Lennox–Gastaut syndrome (LGS), and 19 had West syndrome. Results: of the 76 patients with LGS, CC was performed in 37 patients (48.7%), lobar resection in 29 (38.2%) and hemispherotomy in 10 (13.2%). Of the 19 patients with West syndrome, respective surgery was performed in 15 patients (78.9%) and CC in 4 (21.1%). Of the patients receiving respective surgery, Engel’s class I outcomes were achieved for 24 of 39 (61.5%) of LGS patients, and for 9 of 15 (60.0%) of West syndrome. Malformations of cortical development were commonly observed, appearing in 73.5% (36/49). In neuropsychiatric tests, 19 of 27 with LGS demonstrated improvement in postoperative cognitive function. More significant intellectual improvement correlated well with shorter epilepsy duration, good seizure outcomes, and decreased number of antiepileptic drugs. Conclusions: epilepsy surgery should be considered in treating childhood intractable EE with expectation of improvement of both seizure and cognitive outcomes, even in cases of LGS. [Copyright &y& Elsevier]

Lennox–Gastaut syndrome (LGS) is a severe form of developmental and epileptic encephalopathy that is highly resistant to treatment with conventional anti-epileptic drugs and non-pharmacological therapies. In the present study, we aimed to investigate the efficacy of long-term, high-dose steroid therapy and its effect on prognosis in children with LGS. This prospective study included patients with LGS who received long-term, high-dose steroid therapy beginning in November 2016. Prednisolone (60 mg per day) was administered for 2 weeks, following which the dosage was reduced to 60 mg on alternate days for 12 weeks. The drug was then slowly tapered over the next 3 months. The primary outcome was a reduction in seizure frequency relative to baseline at 14 weeks. The secondary outcome was whether patients had become seizure-free at 1 year. Among 44 patients, 30 (68.2%) experienced a reduction in seizure frequency of more than 50%, including 26 (59.1%) with complete seizure control who were classified as the responder group. The remaining 14 (31.8%) were classified as the non-responder group after 14 weeks of treatment. Twenty patients (45.5%, 20/44) remained seizure-free after 1 year of treatment. However, 10 patients (33.3%, 10/30) in the responder group relapsed within a year. Improvements in electroencephalography (EEG) findings tended to be consistent with seizure outcomes. All patients had side effects of weight gain and Cushing's face, but most adverse effects were mild and transient. Long-term, high-dose steroid therapy can be considered an effective treatment option for children with intractable LGS. • Long-term, high-dose steroid therapy was effective in treating LGS. • Treatment: 60 mg prednisolone (daily: 2 w; every other: 12 w), followed by tapering. • Thirty (68.2%) patients were responders, including 26 who became seizure-free. • Most adverse effects were mild to transient and treatable. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]