Epilepsia
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A mutation in the β(1) subunit of the voltage-gated sodium (Na(V)) channel, β(1) (C121W), causes genetic epilepsy with febrile seizures plus (GEFS+), a pediatric syndrome in which febrile seizures are the predominant phenotype. Previous studies of molecular mechanisms underlying neuronal hyperexcitability caused by this mutation were conducted at room temperature. The prevalence of seizures during febrile states in patients with GEFS+, however, suggests that the phenotypic consequence of β(1) (C121W) may be exacerbated by elevated temperature. We investigated the putative mechanism underlying seizure generation by the β(1) (C121W) mutation with elevated temperature. ⋯ Temperature-dependent changes found in our study are consistent with increased neuronal excitability of GEFS+ patients harboring C121W. These results suggest a novel seizure-causing mechanism for β(1) (C121W): increased channel excitability at elevated temperature.
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Review Meta Analysis
Identification of new epilepsy treatments: issues in preclinical methodology.
Preclinical research has facilitated the discovery of valuable drugs for the symptomatic treatment of epilepsy. Yet, despite these therapies, seizures are not adequately controlled in a third of all affected individuals, and comorbidities still impose a major burden on quality of life. The introduction of multiple new therapies into clinical use over the past two decades has done little to change this. ⋯ New therapies also need to address the special needs of certain subpopulations, that is, age- or gender-specific treatments. Preclinical development in these treatment areas is complex due to heterogeneity in presentation and etiology, and may need to be formulated with a specific seizure, epilepsy syndrome, or comorbidity in mind. The aim of this report is to provide a framework that will help define future guidelines that improve and standardize the design, reporting, and validation of data across preclinical antiepilepsy therapy development studies targeting drug-resistant seizures, epileptogenesis, and comorbidities.
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This critical review refers to the new report on terminology and concepts for the organization of epilepsies by the Commission of the International League Against Epilepsy (ILAE). It is unfortunate that most of the proposals in the Commission's report are modified interpretations and nomenclature of previous ILAE classifications; new terms are not better than the old ones, and recent advances have not been incorporated. Hence, the new ILAE report met with considerable dissatisfaction from several expert epileptologists. ⋯ The ILAE should commission consensus of opinion from experts in specific fields in order to define each syndrome. Areas of certainties and uncertainties and of agreements and disagreements should be identified and explained. This approach may be the only way toward achieving a scientifically sound and clinically meaningful organizational system for the epileptic seizures and the epilepsies-a process that would incorporate the tremendous advances in our field and would be accepted by the wider community of clinicians and scientists.
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To evaluate the long-term (up to 5 years exposure) safety and efficacy of lacosamide as adjunctive therapy in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs) in open-label extension trial SP756 (NCT00522275). ⋯ Long-term (up to 5 years) lacosamide treatment was generally well tolerated. The safety profile of lacosamide observed in this trial is consistent with that established in previous double-blind, placebo-controlled trials. Although the open-label trial design limits the analysis of efficacy, long-term reduction in seizure frequency and maintenance of efficacy was observed.
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The temporal evolution of electrographic seizure burden in neonatal hypoxic ischemic encephalopathy.
Hypoxic ischemic encephalopathy (HIE) accounts for 60% of all neonatal seizures. There is emerging evidence that seizures cause additional injury to the developing brain that has sustained hypoxic ischemic injury. Temporal evolution of clinical seizure burden in HIE has been characterized, with maximum clinical seizure burden (the period of maximum seizure activity) being observed between 12 and 24 h of age. The purpose of our study was to investigate the distribution of electrographic seizure burden (the accumulated duration of seizures over a defined time period), following the initial hypoxic ischemic insult. ⋯ Understanding the temporal evolution of seizure burden in HIE contributes further to our understanding of neonatal seizures, helps identify an optimal therapeutic window for seizure treatment, and provides a benchmark against which to measure the efficacy of new and innovative forms of neuroprotection and antiepileptic medication.