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Aim: We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms.Method: All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed.Results: Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO4 ) combination, low dose ACTH, and high dose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO4 combination, high dose ACTH (with/without vitamin B6 ), high dose prednisolone, and low dose ACTH were 'best'.Interpretation: Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms.What This Paper Adds: Adrenocorticotropic hormone and high dose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag. [ABSTRACT FROM AUTHOR]

Aim: To determine whether epilepsy surgery improved health-related quality of life (HRQoL) and whether seizure freedom after surgery mediated the improvement in HRQoL.Method: This multicenter cohort study compared HRQoL after epilepsy surgery to pharmacological management in children with drug-resistant epilepsy (DRE). HRQoL was measured using the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire at baseline and 1-year follow-up. The mediator between treatment type and HRQoL was seizure freedom.Results: Two hundred and thirty-seven patients were recruited (surgery group: n=147 [92 males, 45 females]; pharmacological group: n=90 [53 males, 37 females]). Mean age at seizure onset was 6 years (SD 4y 4mo) in the surgical group and 6 years 1 month (SD 4y) in the pharmacological group. The odds ratio of seizure freedom was higher for the surgery versus pharmacological group (β=4.24 [95% confidence interval {CI}: 2.26-7.93], p<0.001). Surgery had no direct effect on total QOLCE score at 1-year (β=0.24 [95% CI -2.04 to 2.51], p=0.839) compared to pharmacological management, but had an indirect effect on total QOLCE that was mediated by seizure freedom (β=0.92 [95% CI 0.19-1.65], p=0.013), adjusting for baseline total QOLCE score. Surgery had a direct effect on improving social function (p=0.043), and an indirect effect on improving physical function (p=0.016), cognition (p=0.042), social function (p=0.012) and behavior (p=0.032), mediated by seizure freedom.Interpretation: Greater seizure freedom achieved through epilepsy surgery mediated the improvement in HRQoL compared to pharmacological management in children with DRE.What This Paper Adds: Seizure freedom is higher after pediatric epilepsy surgery compared to pharmacologically managed epilepsy. Surgery indirectly improves health-related quality of life (HRQoL) mediated by seizure freedom compared to pharmacological management. Surgery has a direct effect on improving social function relative to pharmacological management. Baseline HRQoL was an important predictor of HRQoL after treatment. [ABSTRACT FROM AUTHOR]

Objectives To explore the existing evidence for anti-convulsant drugs and their routes of administration in treating acute seizures in children and adults when intravenous access is not available. Methods All major databases including Medline via Ovid, PubMed, Cochrane CENTRAL, Embase, and Google Scholar were searched till May 2015. Randomized and quasi-randomized controlled trials comparing two anti-convulsant drugs (at least one comparator being administered through non-intravenous route) for treatment of acute seizures were included. Outcome measures Primary outcome measure was proportion of children with clinical seizure cessation within 10 min of drug administration. Secondary outcome measures were time taken to clinical seizure cessation from the time of admission and from the time of drug administration, and incidence of significant adverse effects. Results Out of the 19,165 citations, 26 studies were finally included. Regarding the primary outcome measure, the quality of evidence was ‘moderate’ for following 3 comparisons: buccal midazolam being superior to per-rectal diazepam (RR 1.14; 95% CI, 1.06–1.24), intra-nasal lorazepam being same as intravenous lorazepam (RR 1.04; 95% CI, 0.89–1.22) and intramuscular paraldehyde (RR 1.22; 95% CI, 0.99–1.52). The quality of evidence was ‘very-low’ for 1 comparison: per-rectal lorazepam being superior to per-rectal diazepam (RR 3.17; 95% CI, 1.63–6.14). The quality of evidence was ‘low’ for following 2 comparisons: sub-lingual lorazepam being inferior to rectal diazepam (RR 0.71; 95% CI, 0.62–0.81), and intranasal midazolam being superior to per-rectal diazepam (RR 1.14; 95% CI, 1.05–1.25). The rest of the comparisons did not show any difference, but the quality of evidence was ‘low’ to ‘very low’. The time to seizure cessation after drug administration was lower in the intravenous group. However, time to seizure cessation after presentation (includes time for drug administration) was lower in the non-intravenous group. Significant adverse effects were infrequently reported and when present, were similar in both the groups. Conclusions When intravenous access is not available, non-intravenous routes of administration of benzodiazepines should be considered for the control of acute seizures in children/adults. The preference may be guided by availability, expertise and social preference. [PROSPERO No: CRD42015019012]. [ABSTRACT FROM AUTHOR]

There is scanty data regarding the efficacy and tolerability of the modified Atkins diet in children with Lennox-Gastaut syndrome. This study was a retrospective review of children with Lennox-Gastaut syndrome treated with the modified Atkins diet from May 2009 and March 2011. The diet was initiated in those children who persisted to have daily seizures despite the use of at least 3 appropriate antiepileptic drugs. Twenty-five children were started on a modified Atkins diet, restricting carbohydrate intake to 10 g/d. After 3 months, 2 patients were seizure-free, and 10/25 children had >50% reduction in seizure frequency. At 6 months, of 11 patients on the diet, 3 were seizure free and 8 had >50% reduction in seizure frequency. At 1 year, all 9 children on diet had >50% reduction in seizure frequency. The side effects of the diet were mild. The modified Atkins diet was found to be effective and well tolerated in children with Lennox-Gastaut syndrome. [ABSTRACT FROM PUBLISHER]

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well‐being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti‐seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed‐effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (β ± SE = 49.91 ± 16.55 ms, p =.003) and number of IEDs (β ± SE = 49.84 ± 12.51 ms, p <.001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p =.009) and improved task performance (β ± SE = −107.43 ± 39.54 ms, p =.007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function. [ABSTRACT FROM AUTHOR]

Purpose This study was planned to develop and evaluate a simple, easy-to-understand variation of the modified Atkins diet, for use by parents with low levels of literacy in children with refractory epilepsy. Methods This study was conducted in two phases. In the first phase, a simplified version of the modified Atkins diet was developed. In the second phase this was evaluated in children aged 2–14 years who had daily seizures despite the appropriate use of at least two anticonvulsant drugs, in an open-label randomized-controlled-trial. Children were randomized to receive either the simplified modified Atkins diet or no dietary intervention for a period of 3 months with the ongoing anticonvulsant medications being continued unchanged in both the groups. Reduction in seizure frequency was the primary outcome-measure. Data was analyzed using intention to treat approach. Adverse effects were also studied. (Clinical trial identifier NCT0189989). Results Forty-one children were randomly assigned to the diet-group, and 40 were assigned to the control-group. Two patients discontinued the diet during the study period. The proportion of children with >50% seizure reduction was significantly higher in the diet group as compared to the control group (56.1% vs 7.5%, p < 0.0001). The proportion of children with 90% seizure reduction was also higher in the diet group (19.5% vs 2%, p = 0.09). Six children in the diet group were seizure free at 3 months compared with two in the control group (p = 0.26). At 3 months, 6 children had constipation and 5 had weight loss. Conclusion A simplified version of the modified Atkins diet was developed for use by parents with low levels literacy. This diet was found to be feasible, efficacious and well tolerated in children with refractory epilepsy. [ABSTRACT FROM AUTHOR]