Background: Patients with supratentorial cavernous malformations (SCMs) commonly present with seizures. First-line treatments for cavernoma-related epilepsy (CRE) include conservative management (antiepileptic drugs (AEDs)) and surgery. We compared seizure outcomes of CRE patients after early (≤6 months) vs. delayed (>6 months) surgery. Methods: We compared outcomes of CRE patients with SCMs surgically treated at our large-volume cerebrovascular center (1 January 2010-31 July 2020). Patients with 1 sporadic SCM and ≥1-year follow-up were included. Primary outcomes were International League Against Epilepsy (ILAE) class 1 seizure freedom and AED independence. Results: Of 63 CRE patients (26 women, 37 men; mean ± SD age, 36.1 ± 14.6 years), 48 (76%) vs. 15 (24%) underwent early (mean ± SD, 2.1 ± 1.7 months) vs. delayed (mean ± SD, 6.2 ± 7.1 years) surgery. Most (32 (67%)) with early surgery presented after 1 seizure; all with delayed surgery had ≥2 seizures. Seven (47%) with delayed surgery had drug-resistant epilepsy. At follow-up (mean ± SD, 5.4 ± 3.3 years), CRE patients with early surgery were more likely to have ILAE class 1 seizure freedom and AED independence than those with delayed surgery (92% (44/48) vs. 53% (8/15), p = 0.002; and 65% (31/48) vs. 33% (5/15), p = 0.03, respectively). Conclusions: Early CRE surgery demonstrated better seizure outcomes than delayed surgery. Multicenter prospective studies are needed to validate these findings.

BACKGROUND: Dravet Syndrome (DS) is a rare and severe form of childhood epilepsy that is often refractory to conventional antiepileptic drugs. Emerging evidence suggests that Cannabidiol (CBD) offer therapeutic benefits for DS. This review aims to evaluate the efficacy and safety of CBD in pediatric patients with DS based on data from ten clinical trials.
METHODS: A review was conducted to identify clinical trials assessing the efficacy and safety of CBD in pediatric patients diagnosed with DS. PubMed, MEDLINE, Scopus, Web of Science, and relevant grey literature were systematically searched for relevant articles up to October 2023, and clinical trials within the last 10 years were included. The search strategy incorporated controlled vocabulary terms and keywords related to \"Cannabidiol,\" \"Dravet Syndrome,\" and \"pediatric patients.\"
RESULTS: The analysis revealed promising efficacy outcomes. Notably, CBD demonstrated substantial reductions in seizure frequency, with some patients achieving seizure freedom. The findings emphasised the consistency of CBD\'s efficacy across different patient subgroups. The safety profile of CBD was generally acceptable, with adverse events often being manageable.
CONCLUSIONS: This review consolidates evidence from multiple clinical trials, affirming the potential of CBD as a promising treatment option for pediatric patients with DS. While further research is needed to address existing knowledge gaps, CBD\'s efficacy and acceptable safety profile make it a valuable addition to the therapeutic tools for DS.

OBJECTIVE: The objective of this meta-analysis was to determine whether maternal exposure to folate antagonists is associated with increased rates of congenital heart disease in offspring.
METHODS: A comprehensive search for articles in the MEDLINE (PubMed) and EMBASE databases published up to 21 August 2023 was performed. The search strategy was not limited by study design but only for articles in the English language.
RESULTS: Analysis of 6 cohort studies and 5 cross-sectional studies, published between 1976 and 2020, showed significant increase in rate of congenital heart disease (odds ratio 1.55, 95% confidence interval, 1.28-1.87) when exposed to folate antagonists compared with the control. Further subgroup analysis showed the increased rate for exposure to both dihydrofolate reductase inhibitors and antiepileptic drugs separately. No differences were observed when analyses were stratified by timing of study.
CONCLUSIONS: Administration of folate antagonists within the 12-week period preceding conception and throughout the second and third months of gestation exhibited a statistically significant elevation in the susceptibility to congenital heart diseases. Notably, the protective effect of folic acid supplementation was reported in cases of congenital heart disease linked to dihydrofolate reductase inhibitors but not that associated with antiepileptic drugs.

BACKGROUND:  Epilepsy is caused by dysfunction in the brain, which is characterized by an enduring disposition for unprovoked seizures that reoccur often, along with the neurological, cognitive, psychological, and social effects of the condition, which are often managed with prolonged and sometimes lifelong medications that involve antiepileptic drugs (AEDs). To confirm the diagnosis of epilepsy, at least two unprovoked seizures occurring greater than 24 hours apart should be reported. This illness affects both children and adults. Patients with epilepsy are more likely to experience sexual dysfunction compared to the general population, which often leads to a poor quality of life. The pathophysiology involved consists of the impact of epilepsy and AEDs on the control of the hypothalamic-pituitary-gonadal axis, consequently resulting in a high risk of developing testicular or ovarian dysfunction, leading to sexual dysfunction in epilepsy patients.
OBJECTIVE:  This review aims to highlight various studies focusing on the association of developing the risk of sexual dysfunction with psychiatric comorbidities, mainly depression and anxiety, that impact the quality of life in epilepsy patients.
METHODS:  The search methodology involved articles from the Google Scholar and PubMed databases published between 2018 and 2023. \"Sexual dysfunction\", \"epilepsy\", \"depression\", \"anxiety\", and \"quality of life\" were the keywords used to search the articles. The Boolean operator \"AND\" and \"OR\" were used in between the keywords used. Following this, a total of 15 articles were included in the review based on the inclusion and exclusion criteria.
CONCLUSIONS:  The review concluded that epilepsy patients are often affected by sexual dysfunction along with associated psychiatric comorbidities that mainly involve depression and anxiety, consequently impacting their quality of life, as demonstrated by various studies. Sexual dysfunction is a common yet underdiagnosed condition in epilepsy patients due to the stigma attached to it. Hence, neurologists must keep a high index of suspicion for this problem. Furthermore, screening and monitoring for sexual dysfunction should be added to the usual epilepsy work-up.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) accounts for less than 5% of primary brain tumors. Epileptic seizures are a common manifestation of brain tumors; however, literature on the prevalence, characteristics, and oncological implications of seizures in patients with PCNSL is limited, and the management of antiepileptic drugs (AEDs) is unclear. This review aimed to summarize the existing knowledge on seizures in PCNSL, their potential association with surgery, oncological treatment, survival rates, and management of AEDs.
METHODS: A systematic review was performed according to the PRISMA recommendations and included articles published between 1953 and 2023 describing seizures in patients with PCNSL.
RESULTS: The search identified 282 studies, of which 21 were included. Up to 33% of patients with PCNSL developed seizures, mostly at the initial presentation. Little information was found on changes in seizure incidence through the course of the disease, and no details were found on seizure frequency, the percentage of treatment-resistant patients, or the evolution of seizures at remission. Younger age, cortical location, and immunodeficiency have been identified as potential risk factors for seizures, but evidence is very limited. The growing use of vigorous treatments including intensive chemotherapy with autologous stem cell transplantation and immunotherapy with CAR-T cells is associated with a higher incidence of seizures. The association between seizure development and patient mortality in PCNSL remains unknown. There are no data on AED prophylaxis or the use of specific AEDs in PCNSL.
CONCLUSIONS: Further studies are needed to investigate seizures in larger cohorts of PCNSL, to clarify their prevalence, better characterize them, identify risk factors, analyze survival rates, and make recommendations on AED management. We recommend following general practice guidelines for seizures symptomatic of brain tumors and not to prescribe AED prophylaxis in PCNSL.

OBJECTIVE: Antiseizure medications (ASMs) are commonly categorized as enzyme-inducers and non-enzyme-inducers based on their propensity to enhance the metabolism of concomitantly administered drugs. This systematic review and network meta-analysis aimed to rank ASMs as cytochrome P450 3A (CYP3A)-inducers based on a comparative assessment of ASM-induced reduction in the concentrations of sensitive substrate drugs.
METHODS: The protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42022335846), and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) standards were followed. We searched MEDLINE, Embase, and Cochrane until March 14, 2023 without an initial date restriction. Data were additionally obtained via the US Food and Drug Administration database. Studies had to be prospective, with ASM monotherapy for ≥5 days. The primary parameter was the magnitude of change in the area under the concentration-time curve of CYP3A substrates following treatment with the ASM. The standardized mean difference (SMD) was used as the point estimate for the indirect comparisons between ASMs using the pairwise method. Bias risk was assessed using the PKclin tool.
RESULTS: We identified 14 open-label, fixed-sequence studies with 370 participants. The effect size of 600 mg/day carbamazepine did not differ from those of 300 mg/day phenytoin (SMD = -.06, 95% confidence interval [CI] = -.18 to .07) and 200 mg/day cenobamate (SMD = -.11, 95% CI = -.26 to .04). Carbamazepine at 600 mg/day was the strongest CYP3A-inducer (P-score = .88), followed by carbamazepine 400 mg/day (.83), phenytoin 300 mg/day (.79), and cenobamate 200 mg/day (.73). Eslicarbazepine (800 mg/day) ranked higher than cenobamate 100 mg/day and oxcarbazepine 900 mg/day (.60, .39, and .37, respectively).
CONCLUSIONS: Despite the limited number of studies, our network meta-analysis emphasizes that the magnitude of ASM effects on CYP3A substrate metabolism is a dose-dependent continuum. When possible, ASM classification as inducers should apply cutoff values tailored to the outcome. Prescribers should monitor plasma concentrations or clinical effects of CYP3A substrates and consider selecting concomitant medications accordingly.

BACKGROUND: Seizures in the early postoperative period may impair patient recovery and increase the risk of complications. The aim of this study is to determine whether there is any advantage in postoperative seizure prophylaxis following meningioma resection.
METHODS: This systematic review was conducted in accordance with PRISMA guidelines. PUBMED, Web of Science, Embase, Science Direct, and Cochrane were searched for papers until April 2023.
RESULTS: Among nine studies, a total of 3249 patients were evaluated, of which 984 patients received antiepileptic drugs (AEDs). No significant difference was observed in the frequency of seizure events between patients who were treated with antiepileptic drugs (AEDs) and those who were not. (RR 1.22, 95% CI 0.66 to 2.40; I2 = 57%). Postoperative seizures occurred in 5% (95% CI: 1% to 9%) within the early time period (<7 days), and 9% (95% CI: 1% to 17%) in the late time period (>7 days), with significant heterogeneity between the studies (I2 = 91% and 97%, respectively). In seizure-naive patients, the rate of postoperative seizures was 2% (95% CI: 0% to 6%) in the early period and increased to 6% (95% CI: 0% to 15%) in the late period. High heterogeneity led to the use of random-effects models in all analyses.
CONCLUSIONS: The current evidence does not provide sufficient support for the effectiveness of prophylactic AED medications in preventing postoperative seizures in patients undergoing meningioma resection. This underscores the importance of considering diagnostic criteria and conducting individual patient analysis to guide clinical decision-making in this context.

UNASSIGNED: Compared to the general population, the risk of suicide is three times higher in patients with epilepsy and remains doubled for these patients even after adjusting for sociodemographic correlates of suicide in the absence of mental health comorbidities. Following the United States (US) Food and Drug Administration (FDA) alert prompting a black box warning regarding the association between suicidality and antiepileptic drugs (AEDs), several studies were conducted, the results of which have been ambiguous, with some demonstrating a positive association between suicidality and AEDs, while others did not. This systematic review of literature sought to study the relationship between suicidality and AEDs when used exclusively for treatment of epilepsy.
UNASSIGNED: A comprehensive literature search was conducted on PubMed without time limits using a predefined search language. The search results were then subjected to a systematic screening process. Eight out of a total of 443 articles satisfying predefined inclusion and exclusion criteria were included in the review for final data extraction.
UNASSIGNED: Three studies found a significant association between suicide-related behavior and levetiracetam use in the treatment of epilepsy. One study reported a positive association of pregabalin use in patients with epilepsy under 40 years of age and high AED load with suicidality, independent of depression. The remaining four studies reported a significant association between positive family and personal history of psychiatric comorbidities and suicidality in epilepsy.
UNASSIGNED: Although there were several methodological limitations, this review found an association between levetiracetam use and mental health comorbidities and the occurrence of suicidality in epilepsy. Larger prospective, randomized studies that overcome the limitations of current studies are required to provide definitive evidence on the occurrence of suicidality in patients with epilepsy and AED use.

Background: Intractable epilepsy (IE) is still a major concern in neurology, and existing therapies do not adequately control symptoms. Chinese Herbal Medicine (CHM) has been widely used as an adjunct to antiepileptic drugs (AEDs) for IE. However, because of the contradictory findings reported in previous studies, it is uncertain if the present evidence is robust enough to warrant its usage. The purpose of this meta-analysis was to systematically evaluate the efficacy of the combination of CHM and AEDs for IE. Methods: From inception to September 2021, Medline, Ovid, Embase, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, and Wanfang Database were searched. Only randomized controlled trials (RCTs) that assessed the efficacy of the combination of CHM and AEDs for IE were included. We defined monthly seizure frequency as the primary outcome. The secondary outcomes included the abnormal rate of electroencephalogram (EEG), seizure duration, quality of life (QoL), and adverse events (AEs). Results: Twenty studies with 1,830 patients were enrolled. Most trials had poor methodological quality. The meta-analysis showed that the combination of CHM and AEDs was more efficient than AEDs alone in reducing monthly seizure frequency [MD = -1.26%, 95% CI (-1.62, -0.91); p < 0.00001], the abnormal rate of EEG [RR = 0.66%, 95% CI (0.53, 0.82); p = 0.0002], and improving the QoL [MD = 6.96%, 95% CI (3.44, 10.49); p = 0.0001]. There was no significant difference in seizure duration between groups. Moreover, the combination of CHM and AEDs significantly reduced the AEs [RR = 0.45%, 95% CI (0.32, 0.64); p < 0.00001]. Conclusion: The combination of CHM and AEDs could improve seizure control by reducing monthly seizure frequency and abnormal rate of EEG with a decreased risk of adverse events in patients with IE. However, these findings must be interpreted carefully due to the high or uncertain risk of bias in the included trials. To provide stronger evidence for the use of CHM combined with AEDs in IE, high-quality RCTs will be urgently warranted in the future.

Antiseizure medication (ASM) is the primary treatment for epilepsy. In clinical practice, methods to assess ASM efficacy (predict seizure freedom or seizure reduction), during any phase of the drug treatment lifecycle, are limited. This scoping review identifies and appraises prognostic electroencephalographic (EEG) biomarkers and prognostic models that use EEG features, which are associated with seizure outcomes following ASM initiation, dose adjustment, or withdrawal. We also aim to summarize the population and context in which these biomarkers and models were identified and described, to understand how they could be used in clinical practice. Between January 2021 and October 2022, four databases, references, and citations were systematically searched for ASM studies investigating changes to interictal EEG or prognostic models using EEG features and seizure outcomes. Study bias was appraised using modified Quality in Prognosis Studies criteria. Results were synthesized into a qualitative review. Of 875 studies identified, 93 were included. Biomarkers identified were classed as qualitative (visually identified by wave morphology) or quantitative. Qualitative biomarkers include identifying hypsarrhythmia, centrotemporal spikes, interictal epileptiform discharges (IED), classifying the EEG as normal/abnormal/epileptiform, and photoparoxysmal response. Quantitative biomarkers were statistics applied to IED, high-frequency activity, frequency band power, current source density estimates, pairwise statistical interdependence between EEG channels, and measures of complexity. Prognostic models using EEG features were Cox proportional hazards models and machine learning models. There is promise that some quantitative EEG biomarkers could be used to assess ASM efficacy, but further research is required. There is insufficient evidence to conclude any specific biomarker can be used for a particular population or context to prognosticate ASM efficacy. We identified a potential battery of prognostic EEG biomarkers, which could be combined with prognostic models to assess ASM efficacy. However, many confounders need to be addressed for translation into clinical practice.