Epilepsia
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Review
Epilepsy therapy development: technical and methodologic issues in studies with animal models.
The search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. ⋯ We further discuss the different expectations for studies aiming to meet regulatory requirements to obtain approval for clinical testing in humans. Implementation of the rigorous practices discussed in this report will require considerable investment in time, funds, and other research resources, which may create challenges for academic researchers seeking to contribute to epilepsy therapy discovery and development. We propose several infrastructure initiatives to overcome these barriers.
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Fifteen percent to 25% of patients with refractory epilepsy require invasive video-electroencephalography (EEG) monitoring (IVEM) to precisely delineate the ictal-onset zone. This delineation based on the recorded intracranial EEG (iEEG) signals occurs visually by the epileptologist and is therefore prone to human mistakes. The purpose of this study is to investigate whether effective connectivity analysis of intracranially recorded EEG during seizures provides an objective method to localize the ictal-onset zone. ⋯ In this study we demonstrated the feasibility of correctly localizing the ictal-onset zone from iEEG recordings by using effective connectivity analysis during the first 20 s of ictal rhythmic iEEG activity.
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Multicenter Study
Electroencephalography monitoring in critically ill children: current practice and implications for future study design.
Survey data indicate that continuous electroencephalography (EEG) (CEEG) monitoring is used with increasing frequency to identify electrographic seizures in critically ill children, but studies of current CEEG practice have not been conducted. We aimed to describe the clinical utilization of CEEG in critically ill children at tertiary care hospitals with a particular focus on variables essential for designing feasible prospective multicenter studies evaluating the impact of electrographic seizures on outcome. ⋯ These data provide a systematic assessment of recent CEEG use in critically ill children and indicate variability in practice. The results suggest that multicenter studies are feasible if CEEG monitoring pathways can be standardized. However, the data also indicate that electrographic seizure variability must be considered when designing studies that address the impact of electrographic seizures on outcome.
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Randomized Controlled Trial
A randomized phase III trial of adjunctive zonisamide in pediatric patients with partial epilepsy.
To assess the efficacy and safety/tolerability of adjunctive zonisamide treatment in pediatric patients with partial epilepsy. ⋯ Adjunctive zonisamide treatment was shown to be effective and well tolerated in pediatric patients with partial epilepsy. No new or unexpected safety findings emerged.
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Multicenter Study
Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study.
To examine patterns of use, efficacy, and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE). ⋯ Ketamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE.