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Background: Hemiconvulsion-hemiplegia-epilepsy (HHE) involves infantile-onset acute hemiconvulsive febrile status epilepticus with subsequent unilateral cerebral atrophy and hemiparesis. Chronic epilepsy later develops, typically involving refractory focal seizures; however, the underlying pathophysiology of this epilepsy is not well understood., Patient: We present a boy who had a typical acute presentation of HHE at 23 months, but an unusual evolution to chronic epilepsy in which the initially unaffected hemisphere was significantly abnormal. His initial acute presentation was right-sided hemiconvulsive febrile status epilepticus, with subsequent left cerebral hemiatrophy and hemiparesis affecting the right face, arm and leg. Focal seizures began at 5 years and were refractory to medical treatment. At 9 years, video EEG monitoring showed a striking pattern of interictal slow spike-wave and paroxysmal fast activity, maximal over the right, initially unaffected, hemisphere. He had primarily focal tonic seizures involving left-sided stiffening, also appearing to originate from the right hemisphere. Following left functional hemispherotomy he became seizure-free and parents reported improved cognitive function, attention and quality of life., Discussion: This boy had classic features of Lennox-Gastaut syndrome, but expressed almost exclusively over the right hemisphere, which was initially unaffected in his acute presentation of HHE. His evolution to "hemi-Lennox-Gastaut-like phenotype" illustrates the importance of monitoring chronic epilepsy in patients with HHE; early surgical intervention might prevent pathologic recruitment of bilateral secondary networks leading to the refractory seizures and cognitive impairment associated with Lennox-Gastaut syndrome., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications. No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome. We therefore assessed the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in this population of patients., Methods: In this randomised, double-blind, placebo-controlled trial done at 24 clinical sites in the USA, the Netherlands, and Poland, we investigated the efficacy of cannabidiol as add-on therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome. Eligible patients (aged 2-55 years) had Lennox-Gastaut syndrome, including a history of slow (<3 Hz) spike-and-wave patterns on electroencephalogram, evidence of more than one type of generalised seizure for at least 6 months, at least two drop seizures per week during the 4-week baseline period, and had not responded to treatment with at least two antiepileptic drugs. Patients were randomly assigned (1:1) using an interactive voice response system, stratified by age group, to receive 20 mg/kg oral cannabidiol daily or matched placebo for 14 weeks. All patients, caregivers, investigators, and individuals assessing data were masked to group assignment. The primary endpoint was percentage change from baseline in monthly frequency of drop seizures during the treatment period, analysed in all patients who received at least one dose of study drug and had post-baseline efficacy data. All randomly assigned patients were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02224690., Findings: Between April 28, 2015, and Oct 15, 2015, we randomly assigned 171 patients to receive cannabidiol (n=86) or placebo (n=85). 14 patients in the cannabidiol group and one in the placebo group discontinued study treatment; all randomly assigned patients received at least one dose of study treatment and had post-baseline efficacy data. The median percentage reduction in monthly drop seizure frequency from baseline was 43·9% (IQR -69·6 to -1·9) in the cannibidiol group and 21·8% (IQR -45·7 to 1·7) in the placebo group. The estimated median difference between the treatment groups was -17·21 (95% CI -30·32 to -4·09; p=0·0135) during the 14-week treatment period. Adverse events occurred in 74 (86%) of 86 patients in the cannabidiol group and 59 (69%) of 85 patients in the placebo group; most were mild or moderate. The most common adverse events were diarrhoea, somnolence, pyrexia, decreased appetite, and vomiting. 12 (14%) patients in the cannabidiol group and one (1%) patient in the placebo group withdrew from the study because of adverse events. One patient (1%) died in the cannabidiol group, but this was considered unrelated to treatment., Interpretation: Add-on cannabidiol is efficacious for the treatment of patients with drop seizures associated with Lennox-Gastaut syndrome and is generally well tolerated. The long-term efficacy and safety of cannabidiol is currently being assessed in the open-label extension of this trial., Funding: GW Pharmaceuticals., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

West syndrome (WS) is an infantile epileptic encephalopathy that manifests with infantile spasms (IS), hypsarrhythmia (in ~60% of infants), and poor neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic pathologies (~60%), genetic (12%-15%), or of unknown origin. The current treatment options include hormonal treatment (adrenocorticotropic hormone and high-dose steroids) and the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS. There is a need to identify new therapeutic targets and more effective treatments for WS. Theories about the role of inflammatory pathways in the pathogenesis and treatment of WS have emerged, being supported by both clinical and preclinical data from animal models of WS. Ongoing advances in genetics have revealed numerous genes involved in the pathogenesis of WS, including genes directly or indirectly involved in inflammation. Inflammatory pathways also interact with other signaling pathways implicated in WS, such as the neuroendocrine pathway. Furthermore, seizures may also activate proinflammatory pathways raising the possibility that inflammation can be a consequence of seizures and epileptogenic processes. With this targeted review, we plan to discuss the evidence pro and against the following key questions. Does activation of inflammatory pathways in the brain cause epilepsy in WS and does it contribute to the associated comorbidities and progression? Can activation of certain inflammatory pathways be a compensatory or protective event? Are there interactions between inflammation and the neuroendocrine system that contribute to the pathogenesis of WS? Does activation of brain inflammatory signaling pathways contribute to the transition of WS to Lennox-Gastaut syndrome? Are there any lead candidates or unexplored targets for future therapy development for WS targeting inflammation?, (© 2017 Elsevier Inc. All rights reserved.)

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 © 2013. Published by Elsevier B.V.)