Epilepsia
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Precise outcome data about the surgical therapy of cerebral cavernous malformation (CCM)-associated epilepsy is scarce regarding different epilepsy types, surgical approach, and outcome. Long-term outcome in patients with CCM-associated epilepsy is analyzed in a large single-center series. ⋯ Surgical therapy of CCM-associated seizures and epilepsy can be successful if different surgical techniques according to presurgical evaluation are realized. To prevent clinical worsening into DRE, surgical intervention in CCM-associated epilepsy may be considered early.
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Role of the sodium channel SCN9A in genetic epilepsy with febrile seizures plus and Dravet syndrome.
Mutations of the SCN1A subunit of the sodium channel is a cause of genetic epilepsy with febrile seizures plus (GEFS(+) ) in multiplex families and accounts for 70-80% of Dravet syndrome (DS). DS cases without SCN1A mutation inherited have predicted SCN9A susceptibility variants, which may contribute to complex inheritance for these unexplained cases of DS. Compared with controls, DS cases were significantly enriched for rare SCN9A genetic variants. None of the multiplex febrile seizure or GEFS(+) families could be explained by highly penetrant SCN9A mutations.
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Nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) are electrographic seizures (ESz) that are not associated with overt clinical seizure activity. NCS are distinct ESz, whereas NCSE has ongoing, continuous electrographic seizure activity. Both are common in critically ill patients admitted to hospital intensive care units (ICUs), and studies have shown that about 20% of ICU patients undergoing continuous electroencephalography (cEEG) monitoring will have NCS/NCSE. ⋯ The Treatment of Recurrent Electrographic Nonconvulsive Seizures (TRENdS) Study will compare the efficacy and tolerability of fPHT and lacosamide in patients having NCS as noted by cEEG monitoring. The study is currently open to recruitment and has 13 sites in the United States. A total of 200 subjects will be randomized, 100 to each treatment arm.
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Randomized Controlled Trial Multicenter Study
Concentration-effect relationships with perampanel in patients with pharmacoresistant partial-onset seizures.
Although there is a general paucity of published pharmacokinetic (PK) data for new antiepileptic drugs (AEDs), PK analyses of pooled data from clinical studies of perampanel have recently been presented. We present PK/pharmacodynamic (PD) analyses of pooled data from phase III studies of perampanel describing efficacy and safety as a function of exposure, in order to determine whether a predictable concentration-effect relationship exists for perampanel efficacy and/or adverse events (AEs). The effects of concomitant enzyme-inducing AEDs (EIAEDs) and non-enzyme-inducing AEDs on the exposure, efficacy, and safety of perampanel are also considered. ⋯ PK and PD analyses have played a pivotal role in the clinical development of perampanel as an adjunctive treatment for pharmacoresistant partial-onset seizures. Phase III data suggest that a significant relationship exists between increases in perampanel plasma concentration (i.e., systemic exposure) and reductions in seizure frequency. In addition, increases in perampanel plasma concentration may potentially be associated with increases in AE rates. The model-predicted concentration-safety profile of perampanel does not appear to be affected by patient age, gender, or ethnicity. Although concomitant EIAEDs may influence perampanel PK, they do not appear to alter the relationship between perampanel plasma concentration and seizure frequency. Understanding these relationships between perampanel plasma concentration and clinical response will be valuable in utilizing this novel AED.
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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.