Use Of Antiseizure Medications Research Articles

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<0.01) and cognitive flexibility (β =-1.05z, p<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<0.01), working memory (β =-0.77z, p=0.01), processing speed (β=-1.26z, p<0.01), and flexibility (β =-1.54z, p<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.

Clinical Implications of Various Electroencephalographic Patterns in Post-Stroke Seizures. The Utility of Routine Electroencephalogram.

Objective: Post-stroke seizures (PSS) are one of the major stroke-related complications. Early therapeutic interventions are critical therefore using electroencephalography (EEG) as a predictive tool for future recurrence may be helpful. We aimed to assess frequencies of different EEG patterns in patients with PSS and their association with seizure recurrence and functional outcomes. Methods: All patients admitted with PSS were included and underwent interictal EEG recording during their admission and monitored for seizure recurrence for 24 months. Results: PSS was reported in 106 patients. Generalized slow wave activity (GSWA) was the most frequent EEG pattern observed (n = 62, 58.5%), followed by Focal sharp wave discharges (FSWDs) (n = 57, 55.8%), focal slow wave activity (FSWA) (n = 56, 52.8%), periodic discharges (PDs) (n = 13, 12.3%), and ictal epileptiform abnormalities (n = 6, 5.7%). FSWA and ictal EAs were positively associated with seizure recurrence (p < .001 and p = .015 respectively) and it remained significant even after adjusting for age, sex, stroke severity, stroke subtype, or use of anti-seizure medications (ASMs). Other positive associations were status epilepticus (SE) (p = .015), and use of older ASM (p < .001). FSWA and GSWA in EEG were positively associated with severe functional disability (p = .055, p = .015 respectively). Other associations were; Diabetes Mellitus (p = .034), Chronic Kidney Disease (p = .002), use of older ASMs (p = .037), presence of late PSS (p = .021), and those with Ischemic stroke (p = .010). Conclusions: Recognition and documentation of PSS-related EEG characteristics are important, as certain EEG patterns may help to identify the patients who are at risk of developing recurrence or worse functional outcomes.

Hormonal Changes in Women with Epilepsy.

Epilepsy is a prevalent neurological disorder among women globally, often requiring long-term treatment. Hormonal fluctuations in women with epilepsy (WWE) can have reciprocal effects on epilepsy and antiseizure medications (ASMs), posing significant challenges for WWE. Notably, WWE commonly experience endocrine alterations such as thyroid dysfunctions, low bone metabolism, and reproductive hormone irregularities. On the one hand, the presence of hormones in women with epilepsy affects their susceptibility to epilepsy as well as the metabolism of antiseizure medications in various ways. On the other hand, epilepsy itself and the use of antiseizure medications impact the production, secretion, and metabolism of hormones, resulting in low fertility, increased risk of pregnancy complications, negative offspring outcomes, and so on. In order to develop more precise treatment strategies in the future, it is necessary to comprehend the explicit relationships between hormones, epilepsy, and antiseizure medications, as well as to elucidate the currently known mechanisms underlying these interactions.

Comparative Risk of Major Congenital Malformations With Antiseizure Medication Combinations vs Valproate Monotherapy in Pregnancy.

Valproate should be avoided in pregnancy, but it is the most effective drug for generalized epilepsies. Alternative treatment may require combinations of other drugs. Our objectives were to describe first trimester use of antiseizure medication (ASM) combinations that are relevant alternatives to valproate and determine whether specific combinations were associated with a lower risk of major congenital malformations (MCM) compared with valproate monotherapy. We conducted a population-based cohort study using linked national registers from Denmark, Finland, Iceland, Norway, and Sweden and administrative health care data from the United States and New South Wales, Australia. We described first trimester use of ASM combinations among pregnant people with epilepsy from 2000 to 2020. We compared the risk of MCM after first trimester exposure to ASM combinations vs valproate monotherapy and low-dose valproate plus lamotrigine or levetiracetam vs high-dose valproate (≥1,000 mg/d). We used log-binomial regression with propensity score weights to calculate adjusted risk ratios (aRRs) and 95% CIs for each dataset. Results were pooled using fixed-effects meta-analysis. Among 50,905 pregnancies in people with epilepsy identified from 7.8 million total pregnancies, 788 used lamotrigine and levetiracetam, 291 used lamotrigine and topiramate, 208 used levetiracetam and topiramate, 80 used lamotrigine and zonisamide, and 91 used levetiracetam and zonisamide. After excluding pregnancies with use of other ASMs, known teratogens, or a child diagnosed with MCM of infectious or genetic cause, we compared 587 exposed to lamotrigine-levetiracetam duotherapy and 186 exposed to lamotrigine-topiramate duotherapy with 1959 exposed to valproate monotherapy. Pooled aRRs were 0.41 (95% CI 0.24-0.69) and 1.26 (0.71-2.23), respectively. Duotherapy combinations containing low-dose valproate were infrequent, and comparisons with high-dose valproate monotherapy were inconclusive but suggested a lower risk for combination therapy. Other combinations were too rare for comparative safety analyses. Lamotrigine-levetiracetam duotherapy in first trimester was associated with a 60% lower risk of MCM than valproate monotherapy, while lamotrigine-topiramate was not associated with a reduced risk. Duotherapy with lamotrigine and levetiracetam may be favored to treat epilepsy in people with childbearing potential compared with valproate regarding MCM, but whether this combination is as effective as valproate remains to be determined. This study provides Class II evidence that in people with epilepsy treated in the first trimester of pregnancy, the risk of major congenital malformations is lower with lamotrigine-levetiracetam duotherapy than with valproate alone, but similar with lamotrigine-topiramate.

Effect of anti-epileptic drugs usage on thyroid profile in Egyptian epileptic children

BackgroundThe long-term use of anti-seizure medications (ASMs) adversely affects thyroid, lipid profile and other metabolic functions. Subclinical hypothyroidism and alterations in thyroid hormone serum levels are reported with older ASMs in adults with limited and conflicting data of the influence of ASMs especially newer one on thyroid function in children. This study aimed to investigate the effects of conventional and newer ASMs whether mono or polytherapy on thyroid profile in children with epilepsy and its impact on lipid profile and metabolic functions.ResultsThis study included 155 children with epilepsy (76 on monotherapy and 79 on polytherapy) with mean age of 9.677 ± 3.981 years (54.84% euthyroid, 31.61% hypothyroid, 9.68% subclinical hyperthyroid and 3.87% subclinical hypothyroid) and 78 healthy controls. Children with epilepsy whether on monotherapy or on polytherapy had a statistically significant thyroid profile abnormalities (hypothyroidism, sub-clinical hypothyroidism or sub-clinical hyperthyroidism), dyslipidemia, delayed growth and increase in DBP compared to control group. There was a statistically significant positive correlation between hypothyroidism and dyslipidemia as well as between hypothyroidism and delayed growth and increase in DBP. There was no statistically significant difference between polytherapy and monotherapy regarding thyroid and lipid parameters but children with epilepsy on polytherapy were associated with more statistically significant delay in growth and increase in DBP compared to monotherapy group. Carbamazepine had a statistically significant association with hypothyroidism, increase in DBP and higher total and LDL-cholesterol. Valproic acid had a statistically significant association with sub-clinical hypothyroidism with a positive dose correlation. Levetiracetam (LEV) was associated with a statistically significant lower HDL-cholesterol. All echocardiography data showed no abnormality.ConclusionASMs whether older or newer generations can affect thyroid and lipid profile differently through different mechanisms that are dose and duration dependent regardless of the seizure type and age of the patient. ASMs mainly conventional ones are associated with hypothyroidism, sub-clinical hypothyroidism, sub-clinical hyperthyroidism, dyslipidemia and consequently delayed growth and diastolic blood pressure abnormalities.

Adaptive Dosage Strategy of Levetiracetam in Chinese Epileptic Patients: Focus on Pregnant Women

There is presently no efficient dose individualization strategy for the use of antiseizure medications in epileptic pregnant patients. This study aimed to develop a population pharmacokinetics model for levetiracetam and propose a tailored adaptive individualized dosage strategy for epileptic pregnant patients. A total of 322 levetiracetam plasma concentrations from 238 patients with epilepsy were included, including 216 women with epilepsy (20.83% of whom were pregnant). The levetiracetam plasma concentration was measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were modeled using a nonlinear mixed-effects model. The resultant model served as the basis for simulating the dosage adjustment strategy. A one-compartment model with first-order elimination best described the pharmacokinetic data of levetiracetam. The apparent clearance (CL/F) was 3.43 L/h (95% CI 3.30–3.56) and the apparent volume of distribution was 43.7 L (95% CI 40.4–47.0) for a typical individual of 57.2 kg. Pregnancy and body weight were found to be significant covariates of CL/F of levetiracetam. The recommended regimen of levetiracetam could be predicted by the population pharmacokinetic model based on body weight, gestational age, and the daily dose of levetiracetam taken before pregnancy.

Prophylactic use of anti-seizure medication in patients with Sturge-Weber Syndrome: A systematic literature review

Prophylactic use of anti-seizure medication in patients with Sturge-Weber Syndrome: A systematic literature review

Efficient organisation of the contralateral hemisphere connectome is associated with improvement in intelligence quotient after paediatric epilepsy surgery

ObjectiveAims of epilepsy surgery in childhood include optimising seizure control and facilitating cognitive development. Predicting which children will improve cognitively is challenging. We investigated the association of the pre-operative structural connectome of the contralateral non-operated hemisphere with improvement in intelligence quotient (IQ) post-operatively. MethodsConsecutive children who had undergone unilateral resective procedures for epilepsy at a single centre were retrospectively identified. We included those with pre-operative volume T1-weighted non-contrast brain magnetic resonance imaging (MRI), no visible contralateral MRI abnormalities, and both pre-operative and two years post-operative IQ assessment. The MRI of the hemisphere contralateral to the side of resection was anatomically parcellated into 34 cortical regions and the covariance of cortical thickness between regions was used to create binary and weighted group connectomes. ResultsEleven patients with a post-operative IQ increase of at least 10 points at two years were compared with twenty-four patients with no change in IQ score. Children who gained at least 10 IQ points post-operatively had a more efficiently structured contralateral hemisphere connectome with higher global efficiency (0.74) compared to those whose IQ did not change at two years (0.58, p = 0.014). This was consistent across thresholds and both binary and weighted networks. There were no statistically significant group differences in age, sex, age at onset of epilepsy, pre-operative IQ, mean cortical thickness, side or site of procedure, two year post-operative Engel scores or use of anti-seizure medications between the two groups. ConclusionsSurgical procedures to reduce or stop seizures may allow children with an efficiently structured contralateral hemisphere to achieve their cognitive potential.