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Among children and young adults with the Dravet syndrome, a developmental disorder that is associated with treatment-resistant seizures, cannabidiol reduced the frequency of convulsive seizures but caused sleepiness and elevated liver enzymes in some patients. Seizures are difficult to control in the Dravet syndrome, a rare genetic form of epileptic encephalopathy primarily due to loss-of-function mutations in the SCN1A gene. Interest in cannabidiol for the treatment of epilepsy was generated by media reports of efficacy in children with the Dravet syndrome. 1 Four small trials of cannabidiol had yielded mixed results. 2 – 5 A series of in vitro and in vivo preclinical models of seizure showed that cannabidiol had activity against convulsive seizures. 6 Subsequently, the safety and effectiveness of a standardized oral solution of cannabidiol was tested in an open-label trial involving 214 children and young adults . . .

This randomized trial showed that two different doses of oral cannabidiol resulted in greater reductions in drop-seizure and total-seizure frequencies than placebo among patients with the Lennox–Gastaut syndrome, a severe developmental epileptic encephalopathy.

In children with drug-resistant epilepsy, the rate of freedom from seizures at 1 year was higher with epilepsy surgery than with medical therapy alone. Most measures of cognitive development were better in the surgery group than in the medical-therapy group.

Background Seizures are common in patients with brain tumors, impacting daily life and healthcare burden. In contemporary neuro-oncology practice, levetiracetam is the most commonly prescribed anti-seizure medication (ASM). Although the practice is widely variable, levetiracetam is usually used for 2–3 years following surgery to prevent further seizures. However, the incidence of seizures post antitumoral treatment is relatively low, and the duration of use is not well defined. To address this knowledge gap, the current randomized controlled non-inferiority trial will be conducted comparing a shorter regimen of levetiracetam with the standard long-term schedule. Methods and analysis Patients with newly diagnosed primary brain tumors (brain metastasis excluded) in the supratentorial compartment with a prior history of seizure will be eligible for the study. Adults (> 18 years), within 1 year from surgery, and controlled on levetiracetam monotherapy for 6 months will be randomized in a 1:1 ratio to either standard arm (long course: additional 2 years levetiracetam) or experimental arm (short course: tapered of levetiracetam and stopped). Stratification factors include tumor location, seizure type, histology, grade, and adjuvant therapy. The primary endpoint is 2-year seizure-free survival (SFS); secondary endpoints include seizure impact, quality of life, progression-free survival (PFS), and overall survival (OS). Assuming a 2-year SFS rate of 80%, a total of 431 patients (167 events) will be needed to prove the non-inferiority of the experimental arm (non-inferiority margin of 8%, α = 0.05, power = 80%). Considering an attrition rate of 40% (25% accounting for death and 15% lost to follow-up), the final sample size is 604. Discussion The trial will provide level 1 evidence on the optimal duration of ASM use in primary brain tumors with a history of seizures. If short-term ASM use is non-inferior, it will reduce drug utilization, lower neurotoxicity, improve quality of life, and optimize resource usage. Ethics and dissemination The trial has been approved by the Institutional Ethics Committee of Tata Memorial Centre, Mumbai. Registration Registered with CTRI/2024/06/069498, Clinicaltrials.gov: NCT06442748.

Background Early seizures after craniotomy are significant perioperative complications that can adversely impact patient outcomes. Despite current guidelines advising against the routine use of antiseizure drugs for seizure after craniotomy prevention due to limited efficacy data, many clinicians continue prescribing them. This discrepancy highlights the need for robust evidence to guide clinical practice. This multi-center, randomized clinical trial was designed to investigate the efficacy of perampanel in preventing early seizures after craniotomy. Method This multi-center, open-label, randomized clinical trial will be conducted across five hospitals in Nagoya, Japan, from February 2024 to December 2026. A total of 142 seizure-naive patients with supratentorial brain tumors will be recruited and randomized (1:1) into the treatment and control groups. The treatment group will receive 2 mg of perampanel starting 2 days preoperatively and continuing for 28 days postoperatively, while the control group will receive no antiseizure drugs. The primary outcome is the incidence of seizures within 28 days after craniotomy. Secondary outcomes are length of hospital and intensive care unit stays and postoperative complications. Discussion This study addresses the critical need for evidence-based recommendations regarding antiseizure drug use for preventing early seizures after craniotomy. As the first multi-center, randomized trial evaluating perampanel’s efficacy in this setting, the findings may significantly influence clinical guidelines and perioperative practices. Trial registration This trial was registered with the Japan Registry of Clinical Trials (approval number: jRCTs041230117) on December 18, 2023, a member of the Primary Registry Network of the World Health Organization’s International Clinical Trials Registry Platform.

ObjectivePhenytoin (PHT) is routinely used for seizure prophylaxis in patients with brain tumours during and after craniotomy, despite incomplete evidence. We performed a prospective, randomised study to investigate the significance of prophylactic use of levetiracetam (LEV), in comparison with PHT, for patients with supratentorial tumours in the perioperative period.MethodsPatients were randomised to receive LEV, 500 mg/body every 12 h until postoperative day 7, or PHT, 15–18 mg/kg fosphenytoin followed by 125 mg PHT every 12 h until postoperative day 7. The primary end point was the occurrence of seizures, and secondary end points included the occurrence of haematological and non-haematological adverse events.ResultsOne hundred and forty-six patients were randomised to receive LEV (n=73) or PHT (n=73). The incidence of seizures was significantly less in the LEV group (1.4%) compared with the PHT group (15.1%, p=0.005), suggesting benefit of LEV over PHT. The observed OR for being seizure free in the LEV prophylaxis group relative to the PHT group was 12.77 (95% CI 2.39 to 236.71, p=0.001). In a subgroup analysis of patients who did not have seizures before craniotomy, similar results were demonstrated: the incidence of seizures was 1.9% (LEV) and 13.8% (PHT, p=0.034), and OR was 8.16 (95% CI 1.42 to 154.19, p=0.015). LEV was completed in all cases, although PHT was withdrawn in five patients owing to liver dysfunction (1), skin eruption (2) and atrial fibrillation (2).ConclusionsProphylactic use of LEV in the perioperative period is recommended because it is safe and significantly reduces the incidence of seizures in this period.Trial registration numberUMIN13971.

Background Anti-epileptic drugs are commonly used for seizure prophylaxis after neurological injury. We performed a study comparing intravenous (IV) levetiracetam (LEV) to IV phenytoin (PHT) for seizure prophylaxis after neurological injury. Methods In this prospective, single-center, randomized, single-blinded comparative trial of LEV versus PHT (2:1 ratio) in patients with severe traumatic brain injury (sTBI) or subarachnoid hemorrhage (NCT00618436) patients received IV load with either LEV or fosphenytoin followed by standard IV doses of LEV or PHT. Doses were adjusted to maintain therapeutic serum PHT concentrations or if patients had seizures. Continuous EEG (cEEG) monitoring was performed for the initial 72 h; outcome data were collected. Results A total of 52 patients were randomized (LEV = 34; PHT = 18); 89% with sTBI. When controlling for baseline severity, LEV patients experienced better long-term outcomes than those on PHT; the Disability Rating Scale score was lower at 3 months ( P  = 0.042) and the Glasgow Outcomes Scale score was higher at 6 months ( P  = 0.039). There were no differences between groups in seizure occurrence during cEEG (LEV 5/34 vs. PHT 3/18; P  = 1.0) or at 6 months (LEV 1/20 vs. PHT 0/14; P  = 1.0), mortality (LEV 14/34 vs. PHT 4/18; P  = 0.227). There were no differences in side effects between groups (all P  > 0.15) except for a lower frequency of worsened neurological status ( P  = 0.024), and gastrointestinal problems ( P  = 0.043) in LEV-treated patients. Conclusions This study of LEV versus PHT for seizure prevention in the NSICU showed improved long-term outcomes of LEV-treated patients vis-à-vis PHT-treated patients. LEV appears to be an alternative to PHT for seizure prophylaxis in this setting.

Abstract BackgroundThe use of prophylactic anti-seizure medications (ASMs) in the management of patients with spontaneous intracerebral hemorrhage (sICH) and aneurysmal subarachnoid hemorrhage (aSAH) is controversial.ObjectiveThe purpose of this survey was to better characterize the current state of prophylactic ASM use in sICH and aSAH in North America.MethodsUS and Canadian neurosurgeons, neurologists, and interventional neuroradiologists with an interest in or expertise in the management of neurovascular disease were surveyed using an electronic survey tool.ResultsSeven hundred ninety-four survey requests were sent; responses were received from 103 (13%). The majority of respondents were neurosurgeons (84%). Thirty-eight percent of respondents self-identified as vascular neurosurgeons and 10% self-identified as neurocritical care specialists. Seventy-two percent were in academic practice. When asked their preference for ASM prophylaxis (aSAH, sICH, or both), the most common response was to use prophylaxis in both aSAH and sICH (43, 45%). Twenty-one (22%) did not use routine prophylaxis, while 22 (23%) used prophylaxis only in aSAH and 9 (9%) only in sICH. The majority of practitioners (35, 67%) who answered that they used ASM prophylaxis in sICH, used ASMs selectively. For aSAH, the vast majority (53, 82%) used prophylaxis for all patients. Respondents felt that they were more likely to use ASMs for sICH patients if the sICH was in a cortical location, supratentorial location, or was related to a structural abnormality (e.g., tumor, arteriovenous malformation) Levetiracetam (Keppra) was the most commonly used ASM (73, 99%). When asked whether the statement “Current AHA/ASA Guidelines recommend against the use of prophylactic anticonvulsants in spontaneous ICH” was true or false, 78 (83%) responded correctly that the recommendation is true. Only 24 respondents answered the question as to whether they would be willing to randomize sICH and/or aSAH patients to management with or without ASM prophylaxis. Of these, 13 (54%) said they would be willing to randomize sICH patients, while only 6 (25%) were willing to randomize aSAH patients. There were no statistically significant differences in responses to survey questions when analyzed by practice type (academic versus non-academic) or physician specialty (critical care versus non-critical care, or vascular neurology/neurosurgery versus other).ConclusionThe use of ASMs for seizure prophylaxis after sICH and aSAH remains widespread despite the lack of any specific evidence-based guideline to support the practice. A large-scale randomized controlled trial is needed to add clarity to the practice of prophylactic ASM use in patients with spontaneous intracranial hemorrhage.

IntroductionSeizures are a common complication that leads to neurological deficits and affects outcomes after aneurysmal subarachnoid haemorrhage (aSAH). However, whether to use prophylactic anticonvulsants in patients with aSAH remains controversial. Our study aims to determine whether short-term (7 days) sodium valproate could prevent seizure occurrence and improve neurological function in patients with SAH caused by anterior circulation aneurysm rupture and treated with clipping.Methods and analysisIn this multicentre randomised evaluator-blind placebo-controlled trial, 182 eligible patients with good-grade aSAH planned for surgical clipping will be enrolled from four neurosurgical centres in China. In addition to standard care, patients will be randomly assigned to receive sodium valproate 20 mg/kg daily or matching placebo. After aneurysmal clipping, patients will be followed up at discharge, 90 days and 180 days. The primary outcomes are the incidence of early and late seizures. The secondary outcomes include aSAH-related complications, sodium valproate-related adverse effects, modified Rankin Scale (mRS) (on discharge, at 90 days, 180 days), rate of good outcome (defined as mRS 0–2), all-cause death (at 90 days, 180 days) and Montreal Cognitive Assessment score (at 180 days). All analyses are by intention-to-treat.Ethics and disseminationThis study will be conducted according to the principles of Declaration of Helsinki and good clinical practice guidelines. This trial involves human participants and has been approved by the ethics committee of West China Hospital. Informed consent will be achieved from each included patient and/or their legally authorised representative. Preliminary and final results from this study will be disseminated through manuscript publishing and international congresses presentations. Any protocol amendments will be approved by the ethics committee of West China Hospital and subsequently updated on ChiCTR.Trial registration numberChiCTR.org identifier: ChiCTR2100050161.

There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet representing the most time-proven therapies for seizure control. Recently, preliminary evidence has begun to emerge supporting a potential role for ketogenic diets in treating bipolar disorder. Notably, some patients may struggle to initiate a strict diet in the midst of a mood episode or significant life stressors. The key question addressed by this pilot clinical trial protocol is if benefits can be achieved with a less restrictive diet, as this would allow such an intervention to be accessible for more patients. Recent development of so-called ketone esters, that once ingested is converted to natural ketone bodies, combined with low glycemic index dietary changes has the potential to mimic two foundational components of therapeutic ketosis: high levels of ketones and minimal spiking of glucose/insulin. This pilot clinical trial protocol thus aims to investigate the effect of a ‘ketogenic-mimicking diet’ (combining supplementation of ketone esters with a low glycemic index dietary intervention) on neural network stability, mood, and biomarker outcomes in the setting of bipolar disorder. Positive findings obtained via this pilot clinical trial protocol may support future target engagement studies of ketogenic-mimicking diets or related ketogenic interventions. A lack of positive findings, in contrast, may justify a focus on more strict dietary interventions for future research.