Use Of Antiseizure Medications Research Articles

A Comparison of Treatment Practices for Newborn Seizure Management Across Level II and III Neonatal Intensive Care Units in the United States

BackgroundNeonatal seizures (NS) represent an important clinical manifestation among critically ill infants and are often the first sign of underlying brain injury. Early recognition and treatment are essential to reduce morbidity and mortality. ObjectiveThe present study investigated the NS management and treatment approaches employed by Level II/III neonatal intensive care units (NICUs) across the United States, to identify areas of consensus and variability. MethodsPersonnel associated with Level II/III NICUs were directly surveyed with an electronic questionnaire. Access to neurology specialists, on-site electroencephalography (EEG) monitoring and use of anti-seizure medications was directly queried. A total of 51 NICUs participated in this survey. Results25% of surveyed NICUs reported having an established clinical practice pathway available for treating neonatal seizures. 24% endorsed having written guidelines that provided a formal definition for the concept of “neonatal seizures.” Although the majority of NICUs reported having phenobarbital available for rapid seizure management, most NICUs lacked access to additional anti-seizure medications for treatment escalation. 24% of surveyed NICUs had no access to EEG monitoring available to them on-site. Daytime and overnight access to neurology consultants was limited and variable. ConclusionsFindings were consistent with a lack of equitable access for NS treatment. Areas of potential improvement include development and implementation of a protocol for rapidly treating neonatal seizures that emphasizes enhanced access to EEG and rapid neurology consultation, acknowledging and improving upon resource limitations. These developments may eventually provide earlier detection, evaluation, and treatment of seizures in newborns, contributing to improved long-term outcomes.

Optimizing electroencephalogram duration for efficient detection of epileptiform abnormalities in diverse patient groups: a retrospective study

BackgroundThere is no standardized EEG duration guideline for detecting epileptiform abnormalities in patients, and research on this topic is scarce. This study aims to determine an optimal EEG duration for efficient detection of epileptiform abnormalities across different patient groups.MethodsRetrospective analysis was performed on EEG recordings and clinical data of patients with the first seizure and epilepsy. Patients were categorized based on various factors, including the interval time since the last seizure, use of anti-seizure medication (ASM), and seizure frequency. The detection ratio (DR) of epileptiform abnormalities and latency time for their discovery were calculated. Statistical analyses, including chi-square tests, logistic regression, and survival analysis were utilized to illustrate DR and latency times.ResultsIn whole-night EEG recordings, the DR was 37.6% for the first seizure group and 57.4% for the epilepsy group. Although the maximum latency times were 720 min in both two groups, DR in the first seizure group was distinctly decreased beyond 300 min. Significant factors influencing the DR included the use of ASM in the first seizure group (P < 0.05) and seizure frequency in the epilepsy group (P < 0.001). For epilepsy patients who experience a seizure at least once a month or undergo timely EEG recordings (within 24 h after a seizure), the DR significantly increases, and the maximum latency time is reduced to 600 min (P < 0.001). Additionally, the DR was significantly reduced after 240 min in epilepsy patients who had been seizure-free for more than one year.ConclusionsIn this retrospective study, we observed a maximum latency of 720 min for detecting epileptiform abnormalities in whole-night EEG recordings. Notably, epilepsy patients with a higher seizure frequency or timely EEG recordings demonstrated both a higher detection ratio and a shorter maximum latency time. For patients exhibiting a low detection ratio, such as those experiencing their first seizure or those with epilepsy who have been seizure-free for more than a year, a shorter EEG duration is recommended. These findings underscore the importance of implementing customized EEG strategies to meet the specific needs of different patient groups.

Cenobamate add-on therapy for drug-resistant focal epilepsy.

Although most people with epilepsy achieve complete seizure cessation, approximately one-third of those with the condition continue experiencing seizures despite the use of antiseizure medications (ASMs) given as monotherapy or polytherapy. In this review, we summarised the evidence from randomised controlled trials (RCTs) about cenobamate as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant ASMs. To assess the efficacy and tolerability of add-on oral cenobamate for the treatment of drug-resistant focal-onset seizures, defined as seizures persisting despite treatment with one or more ASMs. We searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2022). In addition, we contacted the manufacturer of cenobamate and experts in the field to enquire after any ongoing or unpublished studies. RCTs comparing add-on cenobamate to placebo or another ASM in people with focal epilepsy uncontrolled by one or more concomitant ASMs. Two review authors independently selected trials for inclusion, extracted data, performed risk of bias assessment, and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were at least a 50% reduction in total seizure frequency, seizure freedom, and the occurrence of adverse events. We used an intention-to-treat approach for our primary analyses. For each outcome we estimated summary risk ratios (RRs) with their 95% confidence intervals (CIs). We summarised the estimates of effects and certainty of the evidence for each outcome in a summary of findings table. We included two studies (659 adult participants, 442 allocated to cenobamate and 217 to placebo). The overall RR for at least a 50% reduction in seizure frequency for add-on cenobamate at any dose compared to placebo was 2.17 (52% versus 24%, 95% CI 1.66 to 2.84; 2 studies, 605 participants; moderate-certainty evidence). The RR for seizure freedom for add-on cenobamate at any dose compared to placebo was 4.45 (16% versus 5%, 95% CI 2.25 to 8.78; 2 studies, 605 participants; moderate-certainty evidence). The RR for the occurrence of adverse events for add-on cenobamate at any dose compared to placebo was 1.14 (77% versus 67%, 95% CI 1.02 to 1.27; 2 studies, 659 participants; moderate-certainty evidence). We judged the two included RCTs as at low or unclear risk of bias. Both studies were sponsored by the drug company that produces cenobamate. Add-on cenobamate is probably better than placebo in reducing the frequency of seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy uncontrolled by one or more concomitant ASMs (moderate level of certainty). Its use is probably associated with an increased risk of adverse events (moderate level of certainty). Further prospective, controlled trials are required to evaluate the efficacy and tolerability of add-on cenobamate compared to other ASMs. The efficacy and tolerability of cenobamate as adjunctive treatment for focal epilepsy in children should be further investigated. Finally, the long-term efficacy and tolerability of add-on cenobamate treatment in people with other epilepsy types (e.g. generalised epilepsy) or specific epilepsy syndromes, as well as its use as monotherapy, require additional study.

Exposure to anti-seizure medication during pregnancy and the risk of autism and ADHD in offspring: a systematic review and meta-analysis.

Evidence of an association between maternal use of anti-seizure medication (ASM) during pregnancy and the risk of autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children is conflicting. This systematic review and meta-analysis aimed to summarize the relationship between fetal exposure to ASM and the development of ASD or ADHD in offspring. A comprehensive literature search was conducted in PubMed and other databases to identify relevant epidemiological studies published from inception until 1 March 2024. Seven cohort studies were included in the meta-analysis. The results showed that maternal exposure to ASMs during pregnancy was associated with an increased risk of ASD [odds ratio (OR): 2.1, 95% confidence interval (CI): 1.63-2.71; p < 0.001] in the general population. This association became weaker (ASD: OR: 1.38, 95% CI: 1.11-1.73; p = 0.004) when the reference group was mothers with a psychiatric disorder or epilepsy not treated during pregnancy. Furthermore, an increased risk of ADHD was observed when the study data adjusted for drug indications were pooled (OR: 1.43, 95% CI: 1.07-1.92; p = 0.015). In subgroup analyses based on individual ASM use, only exposure to valproate preconception was significantly associated with an increased risk of ASD or ADHD. The significant association between maternal ASM use during pregnancy and ASD or ADHD in offspring may be partially explained by the drug indication or driven by valproate.

Maternal and fetal outcomes of antiepileptic treatments during pregnancy: A retrospective study

IntroductionEpilepsy is a disease that affects a significant proportion of the female population worldwide. The management of anti-seizure medications during pregnancy and the potential adverse outcomes to both the mother and fetus represent a significant challenge. This retrospective study aimed to evaluate the impact of anti-seizure medications during pregnancy by comparing maternal and fetal outcomes between pregnant women with and without epilepsy. MethodsA total of 242 participants were analysed, including 112 with epilepsy and 130 healthy pregnant controls. Maternal age, medical history, seizure characteristics, use of anti-seizure medications, and pregnancy history were recorded. Maternal and fetal complications, delivery modes, and perinatal outcomes were evaluated. ResultsA total of 242 patients, including 112 (46.3 %) pregnant women with epilepsy and 130 (53.7 %) healthy pregnant women, were included in the study. Among pregnant patients with epilepsy, 4 (3.5 %) did not use anti-seizure medications, 79 (70.5 %) received monotherapy, and 29 (25.8 %) received polytherapy. The rates of pregnancy termination, spontaneous abortion, and maternal and fetal complications were significantly higher in pregnant women with epilepsy (p = 0.045, p = 0.045, p < 0.001, and p = 0.016, respectively). Folic acid use, planned pregnancy rate and postpartum breastfeeding rate were all statistically lower in pregnant women with epilepsy (p < 0.001, p < 0.001, p < 0.001, respectively). The rates of intensive care unit stay, infants with birth weight less than 2500 g, congenital malformations, and preterm births were significantly higher in babies born to pregnant women with epilepsy (p < 0.001, p = 0.047, p = 0.003, and p = 0.051, respectively). Gestational diabetes mellitus was observed in 4 (13.8 %) and congenital malformations in 4 (14.3 %) of the pregnant women with epilepsy who received polytherapy, and in both cases these rates were statistically higher than those of pregnant women with epilepsy who received monotherapy (p = 0.048 and p = 0.004, respectively). DiscussionThis study demonstrated that pregnancies among women affected by epilepsy have significantly higher rates of maternal and fetal complications, spontaneous abortions, and premature births. Polytherapy with anti-seizure medications is associated with an increased risk of gestational diabetes and congenital anomalies. Notably, folic acid use, planned pregnancy, and postpartum breastfeeding were less common in patients with epilepsy. The most commonly prescribed anti-seizure medications were levetiracetam and lamotrigine. Caesarean section is a common mode of delivery in pregnancies of mothers with epilepsy. ConclusionThese results suggest that epilepsy increases both maternal and fetal complications during pregnancy. Furthermore, the use of anti-seizure medications appears to have a significant impact on pregnancy outcomes. Our findings highlight the need for comprehensive management strategies and informed decision making to reduce risks and optimise maternal and fetal outcomes among women with epilepsy.

Seizure Incidence among Children Hospitalized with COVID-19 during the Omicron Wave

Purpose: Since late 2019, coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. Some children with COVID-19 present with seizures; in particular, studies have reported an increase in seizure episodes during the Omicron wave of the pandemic. This study was performed to describe the clinical characteristics of seizures among children hospitalized with COVID-19 before and during the Omicron wave.Methods: A retrospective cross-sectional study was conducted on all pediatric admissions for COVID-19 at Hospital Tunku Azizah from June 2021 to May 2022.Results: During this period, 1,586 children were admitted with COVID-19, of whom 111 (7.0%) experienced seizures. Patients with seizures were more likely to have a history of seizure (odds ratio [OR], 71.4; 95% confidence interval [CI], 23.7 to 215.2; &lt;i&gt;P&lt;/i&gt;&lt;0.001) and prior antiseizure medication use (OR, 55.1; 95% CI, 6.1 to 497.4; &lt;i&gt;P&lt;/i&gt;&lt;0.001). Most seizures (55.0%) occurred on the first day of illness, with 86.5% lasting less than 5 minutes. None of the children required intubation or admission to the pediatric intensive care unit, and all were discharged without complications. Between June 2021 and January 2022, the seizure rate varied from 1.3% to 3.4%; however, it increased to 18% in April 2022, coinciding with the period of Omicron variant predominance in Malaysia. Children admitted during the Omicron wave had significantly higher odds of experiencing seizures (OR, 7.89; 95% CI, 2.07 to 13.07; &lt;i&gt;P&lt;/i&gt;&lt;0.001) than children hospitalized prior to this wave.Conclusion: In conclusion, the study revealed a marked increase in seizures associated with pediatric COVID-19 cases during the Omicron wave.

Treatment effects in epilepsy: a mathematical framework for understanding response over time.

Epilepsy is a neurological disorder characterized by recurrent seizures, affecting over 65 million people worldwide. Treatment typically commences with the use of anti-seizure medications, including both mono- and poly-therapy. Should these fail, more invasive therapies such as surgery, electrical stimulation and focal drug delivery are often considered in an attempt to render the person seizure free. Although a significant portion ultimately benefit from these treatment options, treatment responses often fluctuate over time. The physiological mechanisms underlying these temporal variations are poorly understood, making prognosis a significant challenge when treating epilepsy. Here we use a dynamic network model of seizure transition to understand how seizure propensity may vary over time as a consequence of changes in excitability. Through computer simulations, we explore the relationship between the impact of treatment on dynamic network properties and their vulnerability over time that permit a return to states of high seizure propensity. For small networks we show vulnerability can be fully characterised by the size of the first transitive component (FTC). For larger networks, we find measures of network efficiency, incoherence and heterogeneity (degree variance) correlate with robustness of networks to increasing excitability. These results provide a set of potential prognostic markers for therapeutic interventions in epilepsy. Such markers could be used to support the development of personalized treatment strategies, ultimately contributing to understanding of long-term seizure freedom.

QOL-14. EPILEPTIC SEIZURES, ANTI-SEIZURE MEDICATIONS, AND NEUROCOGNITION IN SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Younger age at diagnosis and cranial radiation therapy are associated with neurocognitive late complications in survivors of pediatric brain tumors (PBT). Less is known about the association between neurocognition and epileptic seizures, with the latter affecting 27% of 5-year survivors. This study aimed to explore whether epileptic seizures exacerbate neurocognitive late complications beyond treatment and demographic factors. METHODS Fifty-nine survivors of PBT who had experienced at least one epileptic seizure, and a control group of survivors matched on sex, age at diagnosis, and cancer treatment, all diagnosed at Skåne University Hospital, were included in the study. Demographic and clinical variables, along with neurocognitive measures of verbal and non-verbal reasoning, cognitive processing speed, working memory, and cognitive flexibility were collected from medical records. Neuropsychological scores, assessed on average 3.68 years after diagnosis, were transformed into z-scores employing age-adjusted norms (m=0, sd=1). Generalized linear models, controlling for increased intracranial pressure at diagnosis and tumor localization, were used to analyze the association between epileptic seizures, cumulative use of anti-seizure medications (ASM), and neurocognition. RESULTS Experiencing any type of epileptic seizures was associated with reduced processing speed (β = -0.91z, p&amp;lt;0.01) and cognitive flexibility (β =-1.05z, p&amp;lt;0.01). Treatment with one ASM was associated with reduced cognitive processing speed (β =-0.81z, p=0.03), and treatment with two or more ASM was associated with lower scores on measures of non-verbal reasoning (β =-0.81z, p&amp;lt;0.01), working memory (β =-0.77z, p=0.01), processing speed (β=-1.26z, p&amp;lt;0.01), and flexibility (β =-1.54z, p&amp;lt;0.01). CONCLUSIONS Epileptic seizures and treatment with ASM were both associated with neurocognitive late complications. Optimal seizure management presents a potential modifiable factor for reducing cognitive burden in survivors of PBT.

Socioeconomic differences in use of antiseizure medication in pregnancies with maternal epilepsy: A population-based study from Nordic universal health care systems.

Research points to disparities in disease burden and access to medical care in epilepsy. We studied the association between socioeconomic status (SES) and antiseizure medication (ASM) use in pregnancies with maternal epilepsy. We conducted a cross-sectional study consisting of 21 130 pregnancies with maternal epilepsy identified from Nordic registers during 2006-2017. SES indicators included cohabitation status, migrant background, educational attainment, and household income. Main outcomes were the proportion and patterns of ASM use from 90 days before pregnancy to birth. We applied multiple imputation to handle SES variables with 2%-4% missingness. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using modified Poisson regression with the highest SES category as reference. Mothers with the highest education and the highest income quintile used ASMs least frequently (56% and 53%, respectively). We observed increased risks of ASM discontinuation prior to or during the first trimester for low SES. The risk estimates varied depending on the SES indicator from aRR = 1.27 for low income (95% CI: 1.03-1.57) to aRR = 1.66 for low education (95% CI: 1.30-2.13). Migrant background was associated with ASM initiation after the first trimester (aRR 2.17; 95% CI 1.88-2.52). Low education was associated with the use of valproate during pregnancy in monotherapy (aRR 1.70; 95% CI 1.29-2.24) and in polytherapy (aRR 2.65; 95% CI 1.66-4.21). Low education was also associated with a 37% to 39% increased risk of switching from one ASM to another depending on the ASM used. For the other SES indicators, aRRs of switching varied from 1.16 (foreign origin; 95% CI 1.08-1.26) to 1.26 (not married or cohabiting; 95% CI 1.17-1.36). Low SES was associated with riskier patterns of ASM use: discontinuation, late initiation, and switching during pregnancy. These findings may reflect unplanned pregnancies, disparities in access to preconception counseling, and suboptimal care.

First-trimester use of antiseizure medications and the risk of miscarriage: a population-based cohort study

BackgroundAntiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage.MethodsWe carried out a population-based cohort study using routinely collected healthcare data from...

Evaluation of anti-seizure medications and their serum concentration with regard to cardiovascular risk parameters: A cross-sectional study

ObjectiveEpilepsy is a chronic disease that requires long-term monitoring and treatment. It is suspected that there is a interaction between the use of anti-seizure medications and the risk of cardiovascular disease. The aim of the study is to investigate the association between the intake of phenobarbital, carbamazepine and valproic acid and their serum drug concentrations (SDC) with various cardiovascular risk parameters (homocysteine, folic acid, vitamin B12, total cholesterol (TC), triglycerides, high- and low-density lipoprotein (LDL)). MethodsThis is a cross-sectional study. Data (demographic characteristics and laboratory results) of patients treated for epilepsy in a tertiary care hospital between January 2020 and February 2022 were analyzed retrospectively (n = 2014). Kruskal Wallis, Mann-Whitney U, correlation analysis was used, p < 0.05 was considered statistically significant. ResultsThe median age of patients was 15 years (IQR:8–31) and 48.3 % were women. The highest homocysteine level was found in patients receiving valproic acid, but it was not statistically significant. Patients receiving phenobarbital had the highest levels of folic acid and B12 and the lowest levels of total cholesterol and low-density lipoprotein cholesterol, which was statistically significant. In patients receiving carbamazepine, a moderately negative significant association was found between serum drug concentration and folic acid levels and a moderately positive significant association was found between TC and LDL levels. ConclusionIn our study, the majority of patients were children and adolescents. Regular monitoring of drug serum concentrations and metabolic parameters may be useful to select the safest drug in terms of cardiovascular disease risk. Randomized controlled trials on the long-term effects of anti-seizure treatment are needed.

Stability of transcranial magnetic stimulation electroencephalogram evoked potentials in pediatric epilepsy

Transcranial magnetic stimulation paired with electroencephalography (TMS–EEG) can measure local excitability and functional connectivity. To address trial-to-trial variability, responses to multiple TMS pulses are recorded to obtain an average TMS evoked potential (TEP). Balancing adequate data acquisition to establish stable TEPs with feasible experimental duration is critical when applying TMS–EEG to clinical populations. Here we aim to investigate the minimum number of pulses (MNP) required to achieve stable TEPs in children with epilepsy. Eighteen children with Self-Limited Epilepsy with Centrotemporal Spikes, a common epilepsy arising from the motor cortices, underwent multiple 100-pulse blocks of TMS to both motor cortices over two days. TMS was applied at 120% of resting motor threshold (rMT) up to a maximum of 100% maximum stimulator output. The average of all 100 pulses was used as a “gold-standard” TEP to which we compared “candidate” TEPs obtained by averaging subsets of pulses. We defined TEP stability as the MNP needed to achieve a concordance correlation coefficient of 80% between the candidate and “gold-standard” TEP. We additionally assessed whether experimental or clinical factors affected TEP stability. Results show that stable TEPs can be derived from fewer than 100 pulses, a number typically used for designing TMS-EEG experiments. The early segment (15–80 ms) of the TEP was less stable than the later segment (80–350 ms). Global mean field amplitude derived from all channels was less stable than local TEP derived from channels overlying the stimulated site. TEP stability did not differ depending on stimulated hemisphere, block order, or antiseizure medication use, but was greater in older children. Stimulation administered with an intensity above the rMT yielded more stable local TEPs. Studies of TMS-EEG in pediatrics have been limited by the complexity of experimental set-up and time course. This study serves as a critical starting point, demonstrating the feasibility of designing efficient TMS–EEG studies that use a relatively small number of pulses to study pediatric epilepsy and potentially other pediatric groups.

Early Seizure Prophylaxis in Mild and Moderate Traumatic Brain Injury

Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial. To determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI. PubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched. Observational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction. The main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI. A total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients. Seizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.

Risk factors for infection and outcomes in infants with neonatal encephalopathy: a cohort study.

To determine the association between early infection risk factors and short-term outcomes in infants with neonatal encephalopathy following perinatal asphyxia (NE). A retrospective population-based cohort study utilizing the National Neonatal Research Database that included infants with NE admitted to neonatal units in England and Wales, Jan 2008-Feb 2018. one or more of rupture of membranes >18 h, maternal group B streptococcus colonization, chorioamnionitis, maternal pyrexia or antepartum antibiotics. death or nasogastric feeds/nil by mouth (NG/NBM) at discharge. organ dysfunction; length of stay; intraventricular hemorrhage; antiseizure medications use. 998 (13.7%) out of 7265 NE infants had exposure to early infection risk factors. Primary outcome (20.3% vs. 23.1%, OR 0.87 (95% CI 0.71-1.08), p = 0.22), death (12.8% vs. 14.0%, p = 0.32) and NG/NBM (17.4% vs. 19.9%. p = 0.07) did not differ between the exposed and unexposed group. Time to full sucking feeds (OR 0.81 (0.69-0.95)), duration (OR 0.82 (0.71-0.95)) and the number of antiseizure medications (OR 0.84 (0.72-0.98)) were lower in exposed than unexposed infants after adjusting for confounders. Therapeutic hypothermia did not alter the results. Infants with NE exposed to risk factors for early-onset infection did not have worse short-term adverse outcomes. Risk factors for early-onset neonatal infection, including rupture of membranes >18 h, maternal group B streptococcus colonization, chorioamnionitis, maternal pyrexia or antepartum antibiotics, were not associated with death or short-term morbidity after cooling for NE. Despite exposure to risk factors for early-onset neonatal infection, infants with NE reached oral feeds earlier and needed fewer anti-seizure medications for a shorter duration than infants with NE but without such risk factors. This study supports current provision of therapeutic hypothermia for infants with NE and any risk factors for early-onset neonatal infection.

Psychiatric and behavioral concerns of perampanel with concomitant levetiracetam in children with epilepsy

PurposePerampanel (PER) is expanding the therapeutic scope for pediatric epilepsy owing to its efficacy and favorable safety profile. However, concerns about psychiatric and behavioral adverse events (PBAEs) in combination therapy with levetiracetam (LEV) continue to contribute to hesitation in its prescription. We investigated the risk profiles for PBAEs when adding PER to pediatric epilepsy treatment and analyzed the differences according to the presence of concomitant LEV. MethodsWe retrospectively reviewed the medical records of children aged 4–18 years with epilepsy who were prescribed PER as adjunctive therapy from March 2016 to February 2023. We compared the occurrence and management of PBAEs between the PER without LEV and PER with LEV groups. The risk factors for PBAEs were also analyzed. ResultsNinety-four patients (53 boys and 41 girls) were included in this study. The median age of total patients at the time of adding PER was 14.9 years (12.3–16.4 years), and 53 patients (56.4 %) had concomitant LEV. Forty-seven PBAEs occurred in 34 patients (36.2 %), with no significant differences depending on whether concomitant LEV is present or not. The most common PBAEs were aggression (14.9 %), irritability (9.6 %), affect lability (7.4 %), and acute psychosis (6.4 %). PBAEs occurred at a lower dosage (2–6 mg/day) in 70.6 % of the patients. In addition, 73.5 % of patients with PBAEs continued PER treatment by follow-up observation or by reducing the PER dosage. No risk factors, such as the presence of concomitant LEV or lamotrigine, any comorbid conditions, higher PER dosage (8–12 mg/day), two or more concomitant anti-seizure medications, and younger age (<13 years) at PER add-on, showed significant associations. ConclusionWhen expanding the use of anti-seizure medications in pediatric patients, real-world evidence on safety issues is crucial for pediatric epileptologists. We confirmed that combination therapy with PER and LEV did not increase the risk profile of PBAEs.

Depot medroxyprogesterone acetate concentrations in patients with and without the use of antiseizure medications

ObjectivesTo measure plasma concentrations of medroxyprogesterone acetate (MPA) in users with epilepsy treated with anti-seizure medications and compare these to MPA concentrations in those without epilepsy. MethodsFor this multi-site cross-sectional study, we obtained a single blood sample from those with epilepsy treated with various anti-seizure medications (n=18) within the week before their next depot medroxyprogesterone (DMPA) injection. Among the participants without epilepsy (n=20), 10 similarly were scheduled within the week prior to the next injection, and 10 were scheduled at earlier intervals to attempt to balance the time intervals between groups. MPA concentrations were determined by a validated assay. ResultsMPA concentrations were similar among those with epilepsy and controls, and between groups with and without use of enzyme-inducing medications. The lowest MPA concentrations, under 0.07 ng/mL, were observed among two of eight using enzyme-inducing anti-seizure medications; one of 10 using non-inducing medications, and one of 19 controls had concentrations below 0.2 ng/mL. ConclusionsIn this exploratory study, lower MPA concentrations in some participants using enzyme-inducing anti-seizure medications suggest a potential interaction that could reduce DMPA efficacy.

Perampanel for the treatment of epilepsy with genetic aetiology: Real-world evidence from the PERMIT Extension study

Genetic factors contribute to the aetiology of epilepsy in >50% of cases, and information on the use of antiseizure medications in people with specific aetiologies will help guide treatment decisions. The PERMIT Extension study pooled data from two real-world studies (PERMIT and PROVE) to investigate the effectiveness and safety/tolerability of perampanel (PER) when used to treat people with focal and generalised epilepsy in everyday clinical practice. This post-hoc analysis of PERMIT Extension explored the use of PER when used to treat individuals presumed to have epilepsy with a genetic aetiology. Assessments included retention rate (evaluated at 3, 6 and 12 months), effectiveness (responder and seizure freedom rates; evaluated at 3, 6, 12 months and the last visit [last observation carried forward) and tolerability (adverse events [AEs]). Of the 6822 people with epilepsy included in PERMIT Extension, 1012 were presumed to have a genetic aetiology. The most common genetic aetiologies were idiopathic generalised epilepsy (IGE; 58.2%), tuberous sclerosis (1.1%), Dravet syndrome (0.8%) and genetic epilepsy with febrile seizures plus (GEFS+; 0.5%). Retention rates at 3, 6 and 12 months in the total genetic aetiology population were 89.3%, 79.7% and 65.9%, respectively. In the total genetic aetiology population, responder rates at 12 months and the last visit were 74.8% and 68.3%, respectively, and corresponding seizure freedom rates were 48.9% and 46.5%, respectively. For the specific aetiology subgroups, responder rates at 12 months and the last visit were, respectively: 90.4% and 84.4% (IGE), 100% and 57.1% (tuberous sclerosis), 100% and 71.4% (Dravet syndrome), and 33.3% and 20.0% (GEFS+). Corresponding seizure freedom rates were, respectively: 73.1% and 64.6% (IGE), 33.3% and 22.2% (tuberous sclerosis), 20.0% and 28.6% (Dravet syndrome), and 0% and 0% (GEFS+). The incidence of AEs was 46.5% for the total genetic aetiology population, 48.8% for IGE, 27.3% for tuberous sclerosis, 62.5% for Dravet syndrome, and 20% for GEFS+. Tolerability findings were consistent with PER’s known safety profile. PER was effective and generally well tolerated when used in individuals with a presumed genetic epilepsy aetiology in clinical practice. PER was effective across a wide range of genetic aetiologies.

Pre-operative predictors of post-operative seizure control in low-grade glioma: a systematic review and meta-analysis.

As many as 80% of low-grade gliomas (LGGs) present with seizures, negatively impacting quality of life. While seizures are associated with gliomas regardless of grade, the importance of minimizing impact of seizures for patients with low grade tumors cannot be understated given the prolonged survival period in this population.The objective of this systematic review and meta-analysis was to summarize existing literature and identify factors associated with post-operative seizure control (defined as Engel I classification) in patients with LGGs, with a focus on pre-operative factors. Patient data extracted include tumor location and histology, pre-operative anti-seizure medication use, extent of resection (EOR), adjuvant treatment, pre-operative seizure type, duration, and frequency, and post-operative Engel classification. A random-effects model was used to calculate the effects of EOR, pre-operative seizure duration, adjuvant radiation, and adjuvant chemotherapy on post-operative seizure control. The effect of tumor location and histology on post-operative Engel I classification was determined using contingency analyses.Thirteen studies including 1628 patients with seizures were included in the systematic review. On meta-analyses, Engel I classification was associated with pre-operative seizure type (OR = 0.79 (0.63-0.99), p = 0.0385, focal versus generalized), frontal lobe LGGs (OR = 1.5 (1.1-2.0), p = 0.0195), and EOR (OR (95% CI) = 4.5 (2.3-6.7), p < 0.0001 gross-total versus subtotal). Pre-operative seizure duration less than one year, adjuvant radiation, adjuvant chemotherapy, and tumor histology were not associated with achieving Engel I classification. In addition to the known effects of EOR, Engel I classification is less likely to be achieved in patients with focal pre-operative seizures and more likely to be achieved in patients with frontal lobe LGGs.

Language impairments in seropositive and seronegative autoimmune encephalitis

Background and objectiveAutoimmune encephalitis (AE) is a rare neuroinflammatory disease affecting the central nervous system. To examine language functions in patients with different subsets of AE consisting of seropositive and seronegative groups.MethodsFifty-two patients were recruited from neurology departments in Melbourne, Australia, who met clinical criteria for possible AE. Language tests include the Naming Test from the Sydney Language Battery (SydBat), the semantic fluency trial from the Controlled Oral Word Association Test (COWAT), and the Vocabulary and Similarities subtests of the Weschler Abbreviated Scale of Intelligence–Second Edition. The results were standardised with normative data.ResultsThe mean age of our cohort was 52.5 years old, with the average time from hospital admission to recruitment being 38.41 months. At an aggregate level, none of the mean language test z-scores were below normative data. At the patient level, impairment rates were 18.37% for COWAT (animals), 28.57% for SydBat (naming), 4.65% for Similarities, and 4.55% for Vocabulary. Chi-squared goodness of fit tests indicated that observed performances were significantly below expected performances for the SydBat (naming) test (p < 0.0001) and COWAT (animals) (p = 0.004).DiscussionWhile, on average, language functions were within normal limits in patients with AE, but a subgroup exhibited lower performance in semantic fluency and visual confrontation naming, with impairment rates below expected norms. To advance understanding of language in chronic AE patients, exploring the impact of seizure burden, antiseizure medication use, and the relationship of language functions with other cognitive functions is crucial.

Benzodiazepines for pediatric epilepsies and their risks in a cohort within the French health care data.

The management of antiseizure treatment in patients with epilepsy relies on the benefit-risk ratio. Data on antiseizure medication (ASM) use in children are limited. We described antiseizure medication use in children with epilepsy (CwE) in France, with a focus on the chronic use of benzodiazepines and related implications. We conducted a 5-year cohort study from January 2012, using data from the French national health care data system (Système National des Données de Santé). We included CwE identified through International Classification of Diseases, 10th Revision codes and medications from January 2012 to December 2015 and followed them until December 2016. We described ASMs and assessed whether the risk of initiating a polytherapy after a bitherapy depends on whether benzodiazepine was included in the bitherapy. We identified 62 885 CwE. Valproate was the most reimbursed ASM (40%), followed by lamotrigine (17.6%), levetiracetam (9.3%), clobazam (6.1%), and carbamazepine (5.8%). Prescriptions were initiated at the hospital in 74.5% of CwE. We observed a decrease in the number of CwE with at least one benzodiazepine reimbursement from 15.3% in 2013 to 10.1% in 2016 (p < .0001). The prevalence of CwE with levetiracetam reimbursements increased, whereas that of CwE with valproate decreased. A switch from a bitherapy to a polytherapy was more likely when the bitherapy included a benzodiazepine (subdistribution hazard ratio [sHR] = 1.20 [1.03-1.39]). The prevalence of CwE with at least one benzodiazepine reimbursement decreased during the study period. Benzodiazepines were associated with an increased use of subsequent ASM polytherapy.