Changes in functional brain network topology after successful and unsuccessful corpus callosotomy for Lennox-Gastaut Syndrome

Corpus callosotomy (CC) is an effective palliative surgical treatment for patients with Lennox-Gastaut Syndrome (LGS). However, research on the long-term functional effects of CC is sparse. We aimed to investigate these effects and their associated clinical conditions over the two years after CC. Long-term clinical EEG recordings of 30 patients with LGS who had good and bad seizure outcome after CC were collected and retrospectively studied. It was found that CC caused brain network 'hubs' to shift from paramedian to lateral regions in the good-recovery group, which reorganized the brain network into a more homogeneous state. We also found increased local clustering coefficients in patients with bad outcomes and decreases, implying enhanced network integration, in patients with good outcomes. The small worldness of brain networks in patients with good outcomes increased in the two years after CC, whereas it decreased in patients with bad outcomes. The covariation of small-worldness with the rate of reduction in seizure frequency suggests that this can be used as an indicator of CC outcome. Local and global network changes during the long-term state might be associated with the postoperative recovery process and could serve as indicators for CC outcome and long-term LGS recovery.ope

Effect of a ketogenic diet on EEG: Analysis of sample entropy

Although ketogenic diet (KD) is an effective alternative therapy for controlling intractable seizures, the anticonvulsant mechanism still remains unclear. Sample entropy (SampEn) provides a generalized measure of regularity in time-series data. To investigate the potential anticonvulsive mechanism of a KD, we analyzed the SampEn of electroencephalography (EEG) data in patients with intractable pediatric epilepsy before and after treatment with a KD. Seventeen pediatric patients with epilepsy who were treated with KD were enrolled in present study. Patients were classified as good responder and poor responder according to therapeutic responsiveness on KD. Thirty segments of 30-s epochs were selected before and after KD from each patient which were subject to SampEn. The KD increased the SampEn in the whole patient population; the SampEn increased significantly in all electrodes in the good responders, but the change in SampEn varied according to the electrode in the poor responders. Before the KD, the good responders had significantly lower SampEn values than the poor responders, but after the KD, SampEn values were higher in the good responders than in the poor responders. KD may have an anticonvulsive effect by decreasing the regularity of the EEG dynamics.ope

Effective and safe diet therapies for Lennox-Gastaut syndrome with mitochondrial dysfunction

Background: Lennox-Gastaut syndrome (LGS) is a typical intractable form of epilepsy that most often occurs between the second and sixth year of life. This study aimed to evaluate the clinical efficacy and safety of ketogenic diet therapies (DTs) for LGS with mitochondrial dysfunction. Methods: This was a retrospective study involving 20 LGS patients with mitochondrial dysfunction who received several DTs from 2004 to 2014 at a single tertiary care center. Seizure reduction rate, cognitive function, retention rate, electroencephalography (EEG) changes, and adverse effects were examined before and after DTs. Results: The retention rates at 1 and 2 years after initiation of DTs were 45% and 40%, respectively. After 1-year follow up, we observed seizure freedom in two patients, 75% seizure reduction in two patients, 50% reduction in three patients, and 25% reduction in one patient. After 2-year follow up, the outcomes were seizure freedom in two patients, 90% seizure reduction in one patient, 75% reduction in two patients, and 50% reduction in two patients. EEG findings improved in nine patients. Nine patients were treated with DTs for 1 year; all patients demonstrated improved cognitive status. Eight patients were treated with DTs for 2 years, of whom seven had improved cognitive status. Poor tolerability of DTs was due to poor oral intake and gastrointestinal problems. Conclusions: We demonstrate that, in LGS with mitochondrial dysfunction, improvement of seizures and cognitive function are not inferior to those in other patients treated with DTs. This study showed that DTs are efficacious and feasible for LGS patients with mitochondrial dysfunction and can significantly improve their prognosis.ope

Updates on the ketogenic diet therapy for pediatric epilepsy

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.ope

Epilepsy : Other Supplementary Treatments

Conventional anti-epileptic treatments have limitations in treating many epileptic patients. Although there have been great advances in the management of epilepsy by application of newly developed anti-convulsants and surgery, some patients still remain in an intractable condition. Other supplementary treatments including immunoglobulin, steroids, and ketogenic diet have significant anti-epileptic potencies. Immunoglobulin treatment shows benefits in some autoimmune-related epileptic conditions such as Rasmussen's encephalitis, however, still has limitations in long-term efficacy. Steroids show significant improvements in many epileptic syndromes including infantile spasm, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and epilepsy with continuous spikes and waves during slow wave sleep, however, some of them recur during or after tapering of the drug. Ketogenic diet has become one of the most reliable treatments for intractable epilepsy especially in children. Ketogenic diet is difficult to maintain because of poor palatability, but shows a very high anti-epileptic efficacy. These supplementary treatments should be considered in various epileptic conditions especially in intractable patients.ope

Diagnostic mutational analysis of MECP2 in Korean patients with Rett syndrome

Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting 1 per 10,000- 15,000 female births worldwide. The disease-causing gene has been identified as MECP2 (methyl- CpG-binding protein 2). In this study, we performed diagnostic mutational analysis of the MECP2 gene in RTT patients. Four exons and a putative promoter of the MECP2 gene were analyzed from the peripheral blood of 43 Korean patients with Rett syndrome by PCR-RFLP and direct sequencing. Mutations were detected in the MECP2 gene in approximately 60.5% of patients (26 cases/43 cases). The mutations consisted of 14 different types, including 9 missense mutations, 4 nonsense mutations and 1 frameshift mutation. Of these, three mutations (G161E, T311M, p385fsX409) were newly identified and were determined to be disease-causing mutations by PCR- RFLP and direct sequencing analysis. Most of the mutations were located within MBD (42.3%) and TRD (50%). T158M, R270X, and R306C mutations were identified at a high frequency. Additionally, an intronic SNP (IVS3+23C>G) was newly identified in three of the patients. IVS3+23C>G may be a disease-related and Korea-specific SNP for RTT. L100V and A201V are apparently disease-causing mutations in Korean RTT, contrary to previous studies. Disease-causing mutations and polymorphisms are important tools for diagnosing RTT in Koreans. The experimental procedures used in this study should be considered for clinical molecular biologic diagnosis.ope

Quality of Life in Childhood Epilepsy and Topiramate

Summary: The primary goal of epilepsy treatment is to enhance patients’ quality of life (QOL) including medical, psychosocial and cognitive function as well as control of seizure. We reviewed the literatures on the objective methods to evaluate QOL and several risk factors for QOL outcome of antiepileptic drug (AED), especially topiramate. Several factors such as age, increased seizure severity, low socioeconomic state, longer duration of AED treatment, side-effect of AED, polytherapy and refractory epilepsy were related to low QOL. Topiramate significantly reduces seizure frequency and improves quality of life including energy/fatigue, anxiety, self-esteem, concentration, memory, language, cognition, social activity, behavior problem and general health in childhood epilepsy.ope

Recent Aspects of Pediatric Epilepsy Surgery

Surgery has been and is now a well-established treatment indicated for adults and children with drug-resistant epilepsy (DRE). The surgical landscape for children with DRE appears to be expanding, and surgical cases of pediatric epilepsy have increased significantly in the past decade, contrary to adult epilepsy. Several fundamental changes have led to the widespread surgical treatment for DRE in children, based on a risk-benefit analysis of pediatric epilepsy surgery, and a change in our overall approach to evaluation. There are unique and age-related differences associated with pediatric epilepsy surgery, characterized by different types of etiologies, concerns for developmental progress, and safety issues. Indications for "pediatric epilepsy surgery" have been broadened to include a wide spectrum of etiologies without excluding children with "generalized" seizures, "generalized or multifocal eletroencephlography", or patients with contra-lateral epileptiform activity or magnetic resonance imaging abnormalities. Furthermore, epilepsy surgery is increasingly considered in infancy and early childhood, which has similar surgical outcomes as the case of late childhood, in an effort to improve the eventual development outcome. Seizure freedom, or at least seizure reduction, is an excellent result with resolution of the associated epileptic encephalopathy, normalization of the EEG, and decrease in the total epileptic burden in the pediatric field.ope

Clinical Features and Treatment Outcomes of Seronegative Pediatric Autoimmune Encephalitis

Background and purpose: New diagnostic criteria for pediatric autoimmune encephalitis (AIE) have been introduced recently. A substantial proportion of cases of pediatric AIE are diagnosed as seronegative based on these criteria, and so the clinical characteristics of this group remain to be investigated. Methods: This study included 46 pediatric patients younger than 18 years with suspected AIE. Clinical features, laboratory or radiological findings, and treatment outcomes were compared between seronegative and seropositive patients. Results: Nine (19.6%) of the 46 patients were diagnosed as seropositive AIE. All of the patients with seropositive AIE had anti-N-methyl-D-aspartate receptor antibodies. Commonly identified neuropsychiatric symptoms were altered mental status, cognitive dysfunction, seizure, speech dysfunction, and psychotic disorder in both the seronegative and seropositive groups. Immunotherapy produced favorable treatment outcomes in both the seropositive (n=7, 77.8%) and seronegative (n=35, 94.6%) AIE patients. Treatment outcomes for first-line immunotherapy were better in seronegative AIE than seropositive AIE patients (p=0.003), and hence a smaller proportion of seronegative patients required second-line treatment (p=0.015). Conclusions: Pediatric seronegative AIE patients showed clinical presentations similar to those of seropositive AIE patients, with favorable treatment outcomes after immunotherapy.ope

Review of clinical studies of perampanel in adolescent patients

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.ope