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Summary 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. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

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]

Abstract: 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 &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

KCNQ2 mutations are associated with benign familial neonatal epilepsy (BFNE) or developmental and epileptic encephalopathy (DEE). In this study, we aimed to delineate the phenotype of KCNQ2 encephalopathy and evaluate the treatment response. Thirteen patients of KCNQ2 encephalopathy were included in the study. Characteristics of KCNQ2 mutations, electroclinical features, clinical course, and response to the treatment were analyzed. Age range of the thirteen patients was between 3 months and 20.9 years. The onset of seizures in 11 patients ranged from 1 to 3 days of age, while in the other two patients it was 7 and 40 days, respectively. Most common initial seizure types were tonic seizures. Initial EEGs were suppression burst pattern in seven patients and slow and disorganized background with multifocal epileptiform discharges in six patients. Initial epilepsy syndrome was Ohtahara syndrome in seven patients, neonatal focal seizure in five patients, and focal epilepsy beyond neonatal period in one patient. Sodium channel blockers including oxcarbazepine (OXC) (n = 3), lamotrigine (LTG) (n = 3), phenytoin (PHT) (n = 2), topiramate (TPM) (n = 2), and zonisamide (ZNS) (n = 1) were tried and found effective in eleven patients. Ultimately, 12 of 13 patients became seizure-free. However, developmental outcomes were poor. Sodium channel blockers are effective in seizure control in these patients with KCNQ2 encephalopathy. Early recognition of KCNQ2 encephalopathy and early use of sodium channel blockers might be helpful in seizure control. [ABSTRACT FROM AUTHOR]

Early-onset developmental and epileptic encephalopathy (DEE) is characterized by repeated seizures beginning within 3 months of birth and severe interictal epileptiform discharge, including burst suppression. This study assessed the utility of targeted gene panel sequencing in the genetic diagnosis of this disease. Targeted gene panel sequencing was performed in 150 early infantile-onset DEE patients (≤3 months of age), and we extensively reviewed their clinical characteristics, including therapeutic efficacy, according to genotype. Of the early infantile-onset DEE patients, 70 were neonatal-onset DEE and the other 80 patients began experiencing seizures from 1 to 3 months after birth. There were 11 different pathogenic or likely pathogenic variants among 34.7% (52/150) of patients with early infantile-onset DEE, in whom KCNQ2 , STXBP1 , CDKL5 , and SCN1A were the major pathogenic variants. Among the neonatal-onset DEE patients, pathological genes were identified in 42.9% (30/70), indicating a significantly higher diagnostic yield than in 27.5% (22/80) of patients who experienced seizure onset 1 to 3 months after birth (p = 0.048). Among the neonatal-onset DEE group, variants in KCNQ2 , STXBP1, and CDKL5 were detected at high frequencies, accounting for 66.7% (20/30) of the pathogenic or likely pathogenic variants found in this study. Targeted gene panel sequencing demonstrated a high yield of pathogenic variants in the diagnosis of early-onset epileptic encephalopathy, especially in those with neonatal-onset DEE. Early diagnosis of early-onset epileptic encephalopathy may improve the prognosis of patients by earlier selection of appropriate treatment based on pathogenic variant. [ABSTRACT FROM AUTHOR]

Abstract 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. [ABSTRACT FROM AUTHOR]

Background We investigated how two distinct mutations in SCN1A differentially affect electrophysiological properties of the patient-derived GABAergic neurons and clinical severities in two Dravet syndrome (DS) patients. Materials and Methods We established induced pluripotent stem cells from two DS patients with different mutations in SCN1A and subsequently differentiated them into forebrain GABAergic neurons. Functionality of differentiated GABAergic neurons was examined by electrophysiological recordings. Results DS-1 patient had a missense mutation, c.4261G > T [GenBank: NM_006920.4 ] and DS-2 patient had a nonsense frameshift mutation, c.3576_3580 del TCAAA [GenBank: NM_006920.4 ]. Clinically, contrary to our expectations, DS-1 patient had more severe symptoms including frequency of seizure episodes and the extent of intellectual ability penetration than DS-2 patient. Electrophysiologic recordings showed significantly lower sodium current density and reduced action potential frequency at strong current injection (>60 pA) in GABAergic neurons derived from both. Intriguingly, unique genetic alterations of SCN1A differentially impacted electrophysiological impairment of the neurons, and the impairment’s extent corresponded with the symptomatic severity of the donor from which the iPSCs were derived. Conclusion Our results suggest the possibility that patient-derived iPSCs may provide a reliable in vitro system that reflects clinical severities in individuals with DS. [ABSTRACT FROM AUTHOR]

Objective Low glycemic index treatment (LGIT) is a newly developed dietary therapeutic option for epilepsy that is less restrictive than the ketogenic diet (KD). Our objective was to determine the efficacy and tolerability of LGIT. Methods From March 2014 to February 2015, 36 patients received LGIT at Severance Children’s Hospital. One-year seizure outcomes and side effects were evaluated. Results A total of 36 patients were assessed. Fourteen were female. Common diagnoses were Lennox-Gastaut syndrome (33%, 12/36) and Dravet syndrome (14%, 5/36). The median age at the initiation of the LGIT was 12.6 years (min. = 1.5, max. = 28, interquartile range (IQR) 8–17). After 3 months of therapy, 20 (56%) patients experienced a 50% or greater reduction in seizure frequency, which was maintained in 19 (53%) patients for 1 year. Two (6%) patients became seizure-free after 3 months of LGIT; they remained seizure-free for 1 year. These two had Dravet syndrome and generalized epilepsy. Only three (8%) patients discontinued treatment within 1 year. Adverse events were rare, and two patients (6%) reported transient diarrhea. Conclusions LGIT effectively reduced seizure frequency in the present study, although seizure freedom was infrequently achieved. LGIT may be considered as a therapeutic option for patients with drug-resistant epilepsy, particularly those who find KD effective but intolerable. [ABSTRACT FROM AUTHOR]

Objective The purpose of the current study was to characterize the frequency profiles of epileptogenic regions, independent of visible epileptiform discharges, in intracranial EEG (iEEG) recordings of Lennox–Gastaut syndrome (LGS) patients. Methods We selected eight LGS patients who underwent resective surgery in the absence of definite neuroimaging findings. We calculated the absolute and relative band powers of continuous spike-free iEEG data and compared the characteristics of the resected and remaining regions. Results For absolute band powers, there was a trend for higher absolute gamma band power in the remaining brain section. We also found that the absolute delta power in the resected area was higher than that in the remaining area. However, this trend was not statistically different in all patients. For relative band powers, we found decreased relative band power in the beta and gamma band ranges within the areas defined by the surgical margins. Delta, theta, and alpha relative band power differences between the resected and remaining areas were inconsistent between the subjects. Conclusions Our results showed systematic relative beta and gamma band power variation in the resected areas of LGS patients. [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]

Abstract: Purpose: This study sought to evaluate the seizure outcome of infantile spasms (IS) with focal cortical dysplasia (FCD). Methods: We retrospectively reviewed infantile spasms patients with FCD from 2004 to 2010. We investigated seizure outcome from antiepileptic drug (AED), ketogenic diet (KD), resective surgery, and analyzed the results according to individual imaging studies. Results: Among 404 patients of IS, FCD was confirmed in 51 patients. In retrospective review of brain MRI, only 21 patients (41.2%) were suspected of FCD before 1year of age, but 45 patients (88.2%) became confirmed to FCD by MRI after the age of 1year. Once the spasms were not controlled by 1 or 2 AEDs, the chance of becoming seizure free with additional third or more drugs was very low (2.3%). The seizure free rate was 33.3% (7/21) in patients treated with ketogenic diet, and 73.3% (22/30) in surgical patients, who were both intractable to AEDs. There were no significant differences in seizure free rate in both ketogenic diet and surgical patients, between MRI negative and positive patients prior to 1year of age. Conclusions: KD and surgery should be considered in medically refractory IS with FCD. [Copyright &y& Elsevier]

Abstract: 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 &y& Elsevier]

Abstract: 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 8weeks, followed by maintenance for 24weeks. 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 &y& Elsevier]

Abstract: 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 1885mg/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 9months), 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 &y& Elsevier]

Abstract: 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 2–17years 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 &y& Elsevier]

Abstract: Purpose: Corpus callosotomy (CC) is a palliative surgical procedure to control atonic, tonic, or generalized tonic–clonic seizure in Lennox–Gastaut syndrome (LGS). Here, we report patients with LGS who underwent resective surgery, following CC better delineating the presumed seizure foci localized in one hemisphere. Methods: We retrospectively reviewed seven patients with LGS who underwent CC and subsequent cortical resection. The median follow-up duration after lobectomy was 20months (range, 15–54months) and three patients had follow-up periods over 24months. The findings of video electroencephalography (EEG) monitoring, structural and functional neuroimagings were compared between pre- and post-CC. Results: Four patients had Engel class I and one patient had Engel class II outcomes following cortical resection; post-CC, compared to pre-CC, showed better localized ictal/interictal epileptiform discharges in the unilateral frontal area in two patients, in the unilateral parieto-temporo-occipital areas in one patient and in the unilateral fronto-temporal areas in the remaining two patients. Two patients had Engel Class III outcome following cortical resection; post-CC EEG continued to show multifocal epileptiform discharges but predominantly arising from a unilateral frontal area. Following CC, positron emission tomography showed localized glucose hypometabolism of which location was concordant with post-CC EEG abnormalities in all patient. Similarly, ictal/interictal single photon emission computed tomography also showed localized abnormalities concordant with post-CC EEG abnormalities in five of the six patients. Pathological assessment revealed cortical dysplasia in six patients, whereas no pathological abnormality was found in the remaining patient, who obtained Engel Class I outcome following cortical resection. Conclusion: CC could change EEG findings, glucose metabolisms and cerebral blood flows, and it is sometimes helpful in delineating the primary seizure focus in patients with LGS. [Copyright &y& Elsevier]

Summary: Purpose: We intended to determine whether transplanted neural precursors, derived from mouse embryonic stem (ES) cells, can migrate and differentiate into mature neurons and glial cells in damaged brains and improve functional deficits caused by global cerebral ischemic injury in adolescent rats. Methods: Global ischemia was induced using the four-vessel occlusion method. ES cells that display enhanced expression of yellow fluorescent protein were co-cultured in N2 supplemented media with PA6 cells that had stromal derived inducing activity. Neural precursor cells were directly transplanted bilaterally into hippocampal C3 areas 2weeks after induction of global ischemia. Assessments of the Morris water-maze test at eight weeks and, the Open field activity levels at two, four, six and eight weeks after transplantation were carried out according to standard methods. Results: From neural precursors, we were able to generate neural lineages, including neurons and glial cells in vitro. Eight weeks following transplantation, cellular migration as well as generation of neural cells including neurons, astrocytes, and oligodendrocytes developed from the grafted ES cell-derived neural precursors were observed. Cell-transplanted animals exhibited enhanced functional recovery on sensorimotor and behavioral tests, compared to vehicle-treated control animals. Conclusion: Therefore, transplantation of mouse ES cell-derived neural precursor cells shows promise for improving recovery after global ischemia in adolescent rats. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

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]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: This study sought to evaluate the efficacy, tolerability, and safety of a ketogenic diet (KD) in the treatment of infantile spasms (IS), incorporating a revised protocol based on our previous experience with KD. We undertook a retrospective analysis of 43 children who suffered from catastrophic IS and tried KD from June 1995 to May 2004 in two Korean epilepsy centers. Outcome measures included seizure frequency, electroencephalograms (EEGs), adverse reactions, and neurological development. Overall, the diet achieved the seizure-free state in 53.5% (23/43) of patients and a greater than 90% reduction of seizure frequency in 62.8% (27/43) of patients. The seizure outcomes were highly concordant with improvements in EEG findings and development. In addition, KD could be maintained more safely and more comfortably because of our revised protocol that included an initial non-fasting diet, a short-term trial of 8 months, a more protein-rich diet with a lipid to non-lipid ratio of 3:1, and liquid ketogenic milk. Most complications were transient and KD was well tolerated in most cases. KD can be an effective alternative therapy for catastrophic IS, and additional benefits may be derived from constant revision of the diet in the future. [Copyright &y& Elsevier]