Real-life evidence about the use of intravenous brivaracetam in urgent seizures: The BRIV-IV study.

PURPOSE: Urgent seizures are a medical emergency for which new therapies are still needed. This study evaluated the use of intravenous brivaracetam (IV-BRV) in an emergency setting in clinical practice. METHODS: BRIV-IV was a retrospective, multicenter, observational study. It included patients ≥18 years old who were diagnosed with urgent seizures (including status epilepticus (SE), acute repetitive seizures, and high-risk seizures) and who were treated with IV-BRV according to clinical practice in 14 hospital centers. Information was extracted from clinical charts and included in an electronic database. Primary effectiveness endpoints included the rate of IV-BRV responder patients, the rate of patients with a sustained response without seizure relapse in 12 h, and the time between IV-BRV administration and clinical response. Primary safety endpoints were comprised the percentage of patients with adverse events and those with adverse events leading to discontinuation. RESULTS: A total of 156 patients were included in this study. The mean age was 57.7 ± 21.5 years old with a prior diagnosis of epilepsy for 57.1% of patients. The most frequent etiologies were brain tumor-related (18.1%) and vascular (11.2%) epilepsy. SE was diagnosed in 55.3% of patients. The median time from urgent seizure onset to IV treatment administration was 60.0 min (range: 15.0-360.0), and the median time from IV treatment to IV-BRV was 90.0 min (range: 30.0-2400.0). Regarding dosage, the mean bolus infusion was 163.0 ± 73.0 mg and the mean daily dosage was 195.0 ± 87.0 mg. A total of 77.6% of patients responded to IV-BRV (66.3% with SE vs. 91% other urgent seizures) with a median response time of 30.0 min (range: 10.0-60.0). A sustained response was achieved in 62.8% of patients. However, adverse events were reported in 14.7%, which were predominantly somnolence and fatigue, with 4.5% leading to discontinuation. Eighty-six percent of patients were discharged with oral brivaracetam. CONCLUSION: IV-BRV in emergency settings was effective, and tolerability was good for most patients. However, a larger series is needed to confirm the outcomes.

Rapid intravenous loading of brivaracetam during invasive and non-invasive video-EEG monitoring.

PURPOSE: The pharmacokinetics of Brivaracetam (BRV) and its ability to penetrate the blood-brain barrier quickly make it a suitable drug for emergencies. In this study, our aim was to investigate the tolerability, safety, and acute efficacy of rapid intravenous (IV) loading of BRV during invasive and non-invasive video-EEG monitoring in patients with drug-resistant focal epilepsy (DRFE). METHODS: Eleven adult patients, six during stereo-electroencephalography (SEEG) and five in scalp video-EEG evaluation, received a 10-minute IV infusion of BRV 100 mg after a period of total withdrawal from antiseizure medications (ASMs). The ictal and interictal EEG activity was assessed through visual and spectrographic analysis before and after intravenous BRV administration. Patients completed the Liverpool Adverse Events Profile (LAEP) scale to evaluate tolerability and adverse events. RESULTS: Rapid BRV IV infusion was well tolerated in all patients. The mean LAEP values showed no significant differences (p = 0.40). Loading BRV resulted in a reduction in interictal activity in six patients. The mean seizure frequency significantly decreased five hours after BRV administration (a 79.2 % reduction across the entire group, p = 0.027). A significant change in spectral band analysis was observed ten minutes after BRV administration. CONCLUSION: Our data suggest that rapid BRV IV infusion has a favorable safety profile and is effective in controlling seizure series in the short term. The electrophysiological changes observed ten minutes after the BRV load correlate with its effects on brain dynamics after blood-brain barrier diffusion.

Mood Disturbances, Anxiety, and Impact on Quality of Life in Patients Admitted to Epilepsy Monitoring Units.

Introduction: The overall combined prevalence of anxiety and depression in patients with epilepsy has been estimated at 20.2 and 22.9%, respectively, and is considered more severe in drug-refractory epilepsy. Patients admitted to epilepsy monitoring units constitute a particular group. Also, patients with psychogenic non-epileptic seizures can reach more than 20% of all admissions. This study aims to characterize these symptoms in a large cohort of patients admitted for evaluation in a tertiary epilepsy center. Materials and Methods: The study was conducted among 493 consecutive patients (age: 38.78 ± 12.7, 57% females) admitted for long-term video EEG from January 2013 to February 2021. Demographic, clinical, and mood disorder patients' data were collected. Anxiety and depression symptoms were assessed through the Hospital Anxiety Depression Scale (HADS-A and HADS-D), the State Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI-II). Quality of life was determined using the QOLIE-10. Patients were divided into three groups: patients with epilepsy (n = 395), psychogenic non-epileptic seizures (PNES) (n = 56), and combined (n = 33). A univariate and multivariate regression analysis was performed for variables associated with quality of life. Results: Of 493 patients, 45.0% had structural etiology, and considering epilepsy classification, 43.6% were of temporal lobe origin. In addition, 32.45% of patients had a previous psychiatric history, 49.9% of patients had depressive symptoms in BDI, and 30.9% according to HADS-D; 56.42 and 52.63% of patients presented pathological anxiety scores in STAI-T and STAI-S, respectively; and 44.78% according to HADS-A. PNES and combined groups revealed a higher incidence of pathologic BDI scores (64.29 and 78.79%, p < 0.001) as well as pathologic HADS-A scores (p = 0.001). Anxiety and depression pathologic results are more prevalent in females, HADS-A (females = 50.7%, males = 36.8%; p = 0.0027) and BDI > 13 (females = 56.6%, males = 41.0%; p = 0.0006). QOLIE-10 showed that 71% of the patients had their quality of life affected with significantly higher scores in the combined group than in the epilepsy and PNES groups (p = 0.0015). Conclusions: Subjective anxiety, depression, and reduced quality of life are highly prevalent in patients with refractory epilepsy. These symptoms are more evident when PNES are associated with epilepsy and more severe among female patients. Most of the cases were not previously diagnosed. These factors should be considered in everyday clinical practice, and specific approaches might be adapted depending on the patient's profile.

Perampanel effect on sleep architecture in patients with epilepsy.

PURPOSE: Among patients with epilepsy, sleep disturbances can worsen seizure control. This prospective open-label study determined the effect of the antiepileptic drug perampanel on sleep architecture in patients with refractory epilepsy. METHODS: Adult patients with refractory epilepsy received add-on perampanel, starting at 2 mg/day at bedtime, increased by 2 mg after 2 weeks and then monthly until the target dose of 4-8 mg/day was reached. The median dose of perampanel used was 6 mg (SD 1.2). Polysomnographic (PSG) recordings were scheduled 1 week before starting perampanel and the control PSG after 12 weeks under perampanel treatment and at least 4 weeks on stable perampanel dose; patients completed the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) questionnaires. The main endpoints were change from baseline in the ESS and PSQI scores, and PSG variables. RESULTS: Of 25 patients included (aged 18-65 years, 56 % female) only 17 completed the study. Perampanel caused a modest decrease from baseline in mean ESS score (n = 13 patients; p = 0.126) and PSQI score (n = 12 patients; p = 0.127). Treatment significantly improved sleep parameters (n = 17 patients) including total sleep time (p = 0.037), sleep latency (p = 0.022), sleep efficiency (p = 0.015), sleep maintenance index (p = 0.005), wake time after sleep onset (p = 0.015), and duration of N3 sleep stage (p = 0.026). Patients with altered sleep efficiency parameters at baseline showed a significant increase in sleep maintenance index (p = 0.015), and 77.8 % achieved sleep efficiency >85 % (p = 0.016 vs baseline). CONCLUSION: Perampanel improved sleep architecture in patients with focal refractory epilepsy without worsening daytime sleepiness.