Search

Objective: We aimed to identify common genes and recurrent causative variants in a large group of Asian patients with different epilepsy syndromes and subgroups. Methods: Patients with unexplained pediatric‐onset epilepsy were identified from the in‐house Severance Neurodevelopmental Disorders and Epilepsy Database. All patients underwent either exome sequencing or multigene panels from January 2017 to December 2019, at Severance Children's Hospital in Korea. Clinical data were extracted from the medical records. Results: Of the 957 patients studied, 947 (99.0%) were Korean and 570 were male (59.6%). The median age at testing was 4.91 years (interquartile range, 1.53–9.39). The overall diagnostic yield was 32.4% (310/957). Clinical exome sequencing yielded a diagnostic rate of 36.9% (134/363), whereas the epilepsy panel yielded a diagnostic rate of 29.9% (170/569). Diagnostic yield differed across epilepsy syndromes. It was high in Dravet syndrome (87.2%, 41/47) and early infantile developmental epileptic encephalopathy (60.7%, 17/28), but low in West syndrome (21.8%, 34/156) and myoclonic‐atonic epilepsy (4.8%, 1/21). The most frequently implicated genes were SCN1A (n = 49), STXBP1 (n = 15), SCN2A (n = 14), KCNQ2 (n = 13), CDKL5 (n = 11), CHD2 (n = 9), SLC2A1 (n = 9), PCDH19 (n = 8), MECP2 (n = 6), SCN8A (n = 6), and PRRT2 (n = 5). The recurrent genetic abnormalities included 15q11.2 deletion/duplication (n = 9), Xq28 duplication (n = 5), PRRT2 deletion (n = 4), MECP2 duplication (n = 3), SCN1A, c.2556+3A>T (n = 3), and 2q24.3 deletion (n = 3). Significance: Here we present the results of a large‐scale study conducted in East Asia, where we identified several common genes and recurrent variants that varied depending on specific epilepsy syndromes. The overall genetic landscape of the Asian population aligns with findings from other populations of varying ethnicities. [ABSTRACT FROM AUTHOR]

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: Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS) is a spectrum of conditions characterized by various phenotypes of cognitive, linguistic, and behavioral regression associated with spike-and-wave activation in sleep. We aimed to investigate the phenotypic spectrum and treatment outcomes of pediatric patients with D/EE-SWAS. Methods: We retrospectively analyzed the medical records of pediatric patients diagnosed with D/EE-SWAS and treated at Severance Children's Hospital from 2006 to 2022. We extracted information from their medical records on electroencephalography before and after treatment, types of treatment, seizure frequency, and developmental profiles. The primary outcome was reduction of the spike-wave index on electroencephalography after treatment. Results: Twenty-one patients with a median age of 5.3 years (interquartile range, 4.1 to 6.6) at diagnosis were included. Ten patients had delayed development. The patients received various anti-seizure medications. Fourteen received long-term, high-dose steroid therapy, 10 were placed on a ketogenic diet, four received intravenous steroid pulse therapy, and one each was treated with intravenous immunoglobulin and cannabidiol. The most effective treatments were steroid therapy and a ketogenic diet, which were also effective in reducing seizures and improving cognition. Side effects during treatment were transient and treatable. Conclusion: We described the clinical spectrum of pediatric patients with D/EE-SWAS. Steroid therapy and a ketogenic diet can be considered effective therapeutic options for patients with D/EE SWAS. [ABSTRACT FROM AUTHOR]

Purpose: In the past, the use of medium-chain triglycerides (MCTs) for a ketogenic diet (KD) was expected to improve both patients' and caregivers' adherence to treatment, but many gastrointestinal problems have been reported. Through a calculated partial administration of MCTs in a KD, we aimed to reduce these complications, while maintaining acceptable seizure reduction. Methods: At a tertiary referral center for pediatric patients with epilepsy, MCT oil was given in a 1:1 ratio with long-chain triglycerides to patients on KDs. Patients who began the diet from February 2019 to February 2020 were reviewed retrospectively, and 47 patients with at least 3 months of follow-up records were enrolled in the study Results: Overall, 29.8% of patients on a KD with an adjusted MCT ratio experienced complications, such as gastrointestinal symptoms and behavioral food refusal, compared to 63.0% of prior KD patients. The mean seizure reduction rate was 68.45%±40.61%, which was not significantly different from the comparison group's rate of 64.84%±34.24%. Conclusion: Adjusted MCT incorporation into a KD showed comparable seizure control results, with better tolerability of the diet. [ABSTRACT FROM AUTHOR]