Potential surgical therapies for drug-resistant focal epilepsy.

Drug-resistant focal epilepsy (DRFE), defined by failure of two antiepileptic drugs, affects 30% of epileptic patients. Epilepsy surgeries are alternative options for this population. Preoperative evaluation is critical to include potential candidates, and to choose the most appropriate procedure to maximize efficacy and simultaneously minimize side effects. Traditional procedures involve open skull surgeries and epileptic focus resection. Alternatively, neuromodulation surgeries use peripheral nerve or deep brain stimulation to reduce the activities of epileptogenic focus. With the advanced improvement of laser-induced thermal therapy (LITT) technique and its utilization in neurosurgery, magnetic resonance-guided LITT (MRgLITT) emerges as a minimal invasive approach for drug-resistant focal epilepsy. In the present review, we first introduce drug-resistant focal epilepsy and summarize the indications, pros and cons of traditional surgical procedures and neuromodulation procedures. And then, focusing on MRgLITT, we thoroughly discuss its history, its technical details, its safety issues, and current evidence on its clinical applications. A case report on MRgLITT is also included to illustrate the preoperational evaluation. We believe that MRgLITT is a promising approach in selected patients with drug-resistant focal epilepsy, although large prospective studies are required to evaluate its efficacy and side effects, as well as to implement a standardized protocol for its application.

Consistent safety and tolerability of Valtoco® (diazepam nasal spray) in relationship to usage frequency in patients with seizure clusters: Interim results from a phase 3, long-term, open-label, repeat-dose safety study.

OBJECTIVE: Need for rescue therapy differs among patients with seizure clusters. Diazepam nasal spray is approved to treat seizure clusters in patients with epilepsy ≥6 years of age. This analysis used interim data from a phase 3 safety study to assess safety profile and effectiveness of diazepam nasal spray using average number of doses/month as a proxy measurement. METHODS: This phase 3, open-label, repeat-dose, safety study of diazepam nasal spray enrolled patients (6-65 years) with epilepsy and need of benzodiazepine rescue. Patients were stratified by average number of doses/month (<2, moderate frequency; 2-5, high frequency; >5, very-high frequency). Safety was evaluated based on treatment-emergent adverse events (TEAEs), assessed nasal irritation, and olfaction. The proportion of treatments given as a second dose was used as an exploratory proxy for effectiveness. RESULTS: Of 175 enrolled patients (data cutoff, October 31, 2019), 158 received ≥1 dose of diazepam nasal spray. Frequency of use was moderate in 43.7% of patients, high in 50.6% of patients, and very high in 5.7% of patients. Patients treated 3397 seizure episodes (moderate frequency, 14.2%; high frequency, 59.9%; very high frequency, 25.8%). Nasal discomfort was the most common treatment-related TEAE in all groups. No notable changes in nasal irritation or olfaction were observed. Second doses represented only 2.5%, 7.5%, and 17.2% of all doses in the moderate-, high-, and very-high-frequency groups, respectively. Overall retention rate was 82.9%, without an observed relationship to frequency of use. SIGNIFICANCE: Frequency of dosing diazepam nasal spray had little impact on the safety/tolerability profile across a range of <2 to >5 doses/month. Effectiveness was suggested for all dosing frequencies by the high proportion of seizure clusters not treated with a second dose. These results support the utility, safety profile, and effectiveness of diazepam nasal spray across frequencies of seizure cluster burden.