Background: Ictal bradycardia (IB) and asystole (IA) represent a rare but potentially harmful feature of epileptic seizures. The aim of this study was to study IB/IA in patients with sleep-related hypermotor epilepsy (SHE). Methods: We retrospectively included cases with video-EEG-confirmed SHE who attended our Institute up to January 2021. We reviewed the ictal polysomnography recordings focusing on ECG and identified cases with IB (R-R interval ≥ 2 s or a ≥10% decrease of baseline heart rate) and IA (R-R interval ≥ 4 s). Results: We included 200 patients (123 males, 61.5%), with a mean age of 42 ± 16 years. Twenty patients (20%) had focal cortical dysplasia (FCD) on brain MRI. Eighteen (out of 104 tested, 17.3%) carried pathogenic variants (mTOR pathway, n = 10, nAchR subunits, n = 4, KCNT1, n = 4). We identified IB/IA in four cases (2%): three had IA (mean 10 s) and one had IB. Three patients had FCD (left fronto-insular region, left amygdala, right mid-temporal gyrus) and two had pathogenic variants in DEPDC5; both features were more prevalent in patients with IB/IA than those without (p = 0.003 and p = 0.037, respectively). Conclusions: We identified IB/IA in 2% of patients with SHE and showed that this subgroup more frequently had FCD on brain MRI and pathogenic variants in genes related to the mTOR pathway.

Seizure clusters (SCs) are an acute and transient increase in seizure frequency relative to an individual patient’s baseline and are associated with an increased risk of injury, morbidity, and potentially mortality if not promptly and adequately treated. Despite their clinical importance, the management of SCs remains highly heterogeneous, primarily due to the absence of a universally accepted definition, which is determined also by the wide variability in seizure semiology and baseline individual burden;, as well as by differences in care settings. Outpatient treatment relies largely on caregivers’ ability to recognize SCs and administer rescue medication, whereas inpatient management may also involve invasive routes of administration. We conducted a literature review identifying 32 original articles addressing the treatment of SCs. The analysis focused on definitions, efficacy outcomes, and adverse events across three clinical scenarios: outpatient, Emergency Department (EDs) and Epilepsy Monitoring Units. The results show that in the outpatient setting, the available evidence suggests that diazepam nasal spray (DZP-NS), midazolam nasal spray (MDZ-NS), and oral lorazepam (LZP) solution may demonstrate comparable efficacy and safety. However, comparisons are limited by heterogeneity in studies’ designs, patient populations and outcome definitions, as well as by the absence of head-to-head trials. Moreover, geographic differences in drug availability (e.g., USA vs. Europe) limit the development of universally applicable treatment protocols. Consequently, the off-label use of oral benzodiazepines, including clobazam, clonazepam, and lorazepam, remains common when oral therapy is feasible, despite limited evidence. The implementation of a patient-specific Acute Seizure Action Plan (ASAP) incorporating an individualized SC definition is recommended. In contrast, inpatient management shows greater consensus, largely reflecting first-line treatment paradigms for status epilepticus. These include prompt intravenous benzodiazepine administration, followed by the intravenous loading of antiseizure medications such as brivaracetam or lacosamide in cases of seizure recurrence. In ED settings, “empirical” definitions of SCs (i.e., more than three seizures within 24 h) may facilitate timely intervention.

Purpose: To evaluate the long-term efficacy of vagus nerve stimulation (VNS) in reducing tonic-clonic seizures (TCS), drop attacks, and seizure clusters in adults with drug-resistant epilepsy (DRE). Methods: This retrospective, single-center study included adults with DRE who received VNS and had ≥ 12 months of follow-up. Data were collected pre-implantation (T0), at 12 months (T1), and last follow-up (T2). Outcomes included reduction in total seizure frequency and severity, frequency of TCS and drop attacks, and frequency/duration of seizure clusters. Battery replacement and tolerability were also assessed. Results: Eighty-seven subjects (51 males, median age 33 at T0) with a mean follow-up of 8 years were analyzed. At T2, 54% showed reduced total seizure frequency and 71% reported decreased severity/duration. Among those with baseline TCS, 75% (T1)–80.6% (T2) had frequency reduction, with 20.6% seizure-free at T2. Drop attacks improved in > 70% of cases, with resolution in 21.8% at T2. Over 80% with seizure clusters reported decreased frequency/duration at both T1 and T2. Response rates for specific seizure types significantly exceeded non-response ( p < 0.001). Battery replacement was required in 85.7% near depletion. Side effects occurred in 49.4%, mostly mild/transient; major complications were rare. Conclusion: VNS exerts a robust effect on the most disabling seizures—TCS, drop attacks, and seizure clusters—surpassing its impact on overall seizure burden. Benefits appear within the first year and persist long term. These findings support a more tailored approach to VNS candidate selection, advocating earlier use in patients with refractory, harmful seizures not eligible for curative surgery.

Purpose: Antiseizure medications (ASMs) are often coprescribed with direct oral anticoagulants (DOACs). The pharmacokinetic (PK) interactions between ASMs and DOACs may result in altered exposure to anticoagulants, potentially increasing the risk of thromboembolic events or bleeding. This review summarizes the clinical evidence on drug–drug interactions between ASMs and DOACs. Methods: In accordance with PRISMA-ScR guidelines, a systematic literature search was conducted in PubMed (up to November 2025). All clinical reports and observational datasets reporting the concomitant use of at least 1 ASM and DOAC were included. ASM–DOAC combinations, PK findings, and reported clinical outcomes are presented. Results: Thirty studies were included. Most reports involved enzyme-inducing ASMs (carbamazepine, phenobarbital, primidone, and oxcarbazepine), which were consistently associated with subtherapeutic DOAC plasma concentrations and severe clinical failures. Doubling the DOAC dose did not prevent these events in several cases. Rivaroxaban and apixaban were the most frequently described DOACs, whereas clinical data for edoxaban were limited. Evidence of non–enzyme-inducing ASMs, such as levetiracetam and valproic acid, was limited. Conclusions: Although enzyme-inducing ASMs compromised DOAC efficacy, the available clinical evidence was fragmented and prone to publication bias. The observed variability in interactions involving noninducing ASMs such as levetiracetam underlines the clinical complexity that may exceed theoretical PK predictions. Given the unpredictability of these interactions and the failure of empirical dose adjustments, a standardized approach for therapeutic drug monitoring and prospective, comparative trials are essential to guide personalized therapy in this high-risk population.

To understand the extent to which women of childbearing age (WoCBA) are aware of the issues associated with epilepsy and pregnancy and identify unmet reproductive healthcare and information needs. WoCBA with epilepsy completed a 34-question online survey (January to March 2021), including sections on demographics, clinical information, and access to reproductive health care. The survey was available in English, Croatian, Czech, Georgian, German, Italian, Polish, Russian and Spanish. Overall, 865 responses were received and included in the analysis. Most respondents were aged 20-39 years (77.0 %), were married (43.6 %) and 63.2 % had been diagnosed with epilepsy for more than 10 years. Over half of respondents (53.9 %) had previously been pregnant, with 75.5 % reporting that they took anti-seizure medication (ASMs) during pregnancy. Most (67.6 %) respondents had received information about epilepsy and pregnancy with 43.4 % of respondents receiving this information before their first pregnancy. Although 71.5 % found the information 'very helpful' or 'somewhat helpful', some respondents found the information frightening, confusing, or difficult to access. Most respondents (74.1 %) had been made aware of the risks of taking some ASMs while pregnant; 59.8 % had been advised to consider pregnancy planning, however, 52.7 % were not provided with information on contraception while taking ASMs. Over half (56.9 %) of respondents felt that clear and concise information was not available for women with epilepsy who were considering becoming pregnant. There is a need to improve education and support for WoCBA with epilepsy to help them with decision-making, planning and managing pregnancy.