OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.

UNASSIGNED: The short- and long-term consequences of restricted fetal growth cause considerable concern, and how prenatal exposure to different antiseizure medications (ASMs) affects fetal growth remains uncertain.
UNASSIGNED: This was a population-based cohort study of liveborn singleton children born in Denmark, Finland, Iceland, Norway, and Sweden from 1996 to 2017. Prenatal exposure was defined as maternal filling of prescriptions for ASM during pregnancy registered in national prescription registries and primary outcomes were adjusted odds ratios (aORs) of microcephaly or being born small for gestational age.
UNASSIGNED: We identified 4,494,918 children (males: 51.3%, 2,306,991/4,494,918), including 38,714 (0.9%) children of mothers with epilepsy. In the overall population, prenatal monotherapy exposure with carbamazepine (aOR: 1.25 (95% CI: 1.12-1.40)), pregabalin (aOR: 1.16 (95% CI: 1.02-1.31)), oxcarbazepine (aOR: 1.48 (95% CI: 1.28-1.71)), clonazepam (aOR: 1.27 (95% CI: 1.10-1.48)), and topiramate (aOR: 1.48 (95% CI: 1.18-1.85)) was associated with risk of being born small for gestational age, and carbamazepine was associated with microcephaly (aOR: 1.43 (95% CI: 1.17-1.75)). In children of mothers with epilepsy, prenatal exposure to carbamazepine (aOR: 1.27 (95% CI: 1.11-1.47)), oxcarbazepine (aOR: 1.42 (95% CI: 1.18-1.70)), clonazepam (aOR: 1.40 (95% CI: 1.03-1.89)), and topiramate (aOR: 1.86 (95% CI: 1.36-2.54)) was associated with being born small for gestational age; carbamazepine, with microcephaly (aOR: 1.51 (95% CI: 1.17-1.95)). No associations with small for gestational age and microcephaly were identified after prenatal exposure to lamotrigine, valproate, gabapentin, levetiracetam, phenobarbital, acetazolamide, phenytoin, clobazam, primidone, zonisamide, vigabatrin, ethosuximide and lacosamide, but except for lamotrigine, valproate, gabapentin, and levetiracetam, numbers of exposed children were small.
UNASSIGNED: Prenatal exposure to carbamazepine, oxcarbazepine, clonazepam, and topiramate was associated with increased risk of being born small for gestational age in both the overall population and in children of women with epilepsy suggesting that prenatal exposure to these drugs is associated with fetal growth restriction.
UNASSIGNED: The NordForsk Nordic Program on Health and Welfare (83539), the Independent Research Fund Denmark (1133-00026B), the Danish Epilepsy Association, the Central Denmark Region, the Novo Nordisk Foundation (NNF16OC0019126 and NNF22OC0075033), and the Lundbeck Foundation (R400-2022-1205).

BACKGROUND: Evidence-based recommendations for antiepileptic drug selection in cats beyond phenobarbital are limited, and additional studies are needed for cats where seizures remain inadequately controlled by administration of phenobarbital alone or for cats that cannot safely receive phenobarbital.
OBJECTIVE: To compare seizure frequency in cats before and after oral administration of zonisamide and describe adverse clinical or clinicopathologic effects in this cohort.
METHODS: Fifty-seven cats with a history of seizures.
METHODS: Multicenter, retrospective study. Median number of seizures per month and number of seizure days per month were compared before and after administration of zonisamide in all cats, a subgroup of cats with idiopathic epilepsy (IE), and a subgroup of cats receiving zonisamide as sole therapy. Clinical and clinicopathologic adverse effect data were also reported.
RESULTS: A median decrease of 1 (P = .001, 95% confidence interval (CI) [-1.0, -0.5]) seizure per month, and 1 (P = .003, 95% CI [-1.5, -0.2]) seizure days per month was found across all cats after oral administration of zonisamide. The subgroup with IE showed median decreases of 1 (P = .03, 95% CI [-2.0, -0.5]) and 2 (P = .01, 95% CI [-2.5, -1.0]), respectively. The most common clinical adverse effects were sedation (17%), ataxia (11%), hyporexia (17%), and emesis (5%). One cat developed mild nonregenerative anemia, 2 cats developed mild metabolic acidosis, and 6 cats showed mild increases in ALT and ALP.
CONCLUSIONS: Zonisamide was well tolerated and efficacious in controlling seizure activity in most cats.

UNASSIGNED: COVID-19 has significantly impacted the care of children with chronic illness. There is a paucity of data on issues faced by parents of children with epilepsy (CWE) in an Indian setup.
UNASSIGNED: The objective was to describe the parental perspective of the problems faced by them on the care of their CWE during the first wave of the COVID-19 pandemic.
UNASSIGNED: Parents of CWE who physically visited the clinic for their follow-up visit were asked to narrate their experiences about the problems they faced during the first lockdown due to COVID-19. The narratives were audio recorded, and transcripts were analyzed using thematic analysis to arrive at broad themes.
UNASSIGNED: Four broad themes were identified: transport-related issues, medication-related issues, issues related to doctor consultation, and diagnostic delay. Limited transportation facilities, lack of appropriate social distancing norms in public transport and outpatient units, rigorous frisking by personnel during travel, fear of viral transmission during outpatient visits, nonavailability of antiseizure medications (ASMs) in local markets, lack of discounts by pharmacy, change of brands of ASM, and inability to undergo scheduled diagnostic investigations were some of the major issues raised by parents of CWE.
UNASSIGNED: Parents of CWE had trouble in transport to the hospital, inadequate access to ASMs, difficulties in doctor consultation, and delays in diagnostic investigations during the first COVID-19 pandemic lockdown.

BACKGROUND: Anticonvulsant drugs are one of the most common causes of delayed hypersensitivity reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). These reactions are more prevalent with aromatic anticonvulsant drugs such as phenytoin and carbamazepine. However, immediate hypersensitivity reactions such as urticaria, angioedema, and anaphylaxis with anticonvulsant drugs are rare. We describe a 51-year-old woman who developed spreading skin rashes on her wrists with urticaria and pruritus 24 h after receiving intravenous levetiracetam.
CONCLUSIONS: Clinicians should be aware of immediate hypersensitivity reactions with intravenous levetiracetam.

OBJECTIVE: Increased mortality in epilepsy due to infections (other than pneumonia) has been demonstrated. Small case series of people on antiepileptic drugs (AEDs) have described hypogammaglobulinaemia, which may predispose to infections. It is unclear whether hypogammaglobulinaemia is more frequent in people on AEDs, what AEDs it is associated with, or what clinical impact it has. In this population-based study, we aimed to determine whether AEDs were associated with hypogammaglobulinaemia, which AEDs were associated, and whether the associations may be causal.
METHODS: We conducted an unmatched case-control study using data linkage of routinely collected biochemistry, prescribing, and morbidity datasets in North-East Scotland from 2009-2021. Cases were participants with immunoglobulin levels less than the reference range. Controls were those with normal/high immunoglobulin levels. Logistic regression was used to investigate associations between AED exposure and any hypogammaglobulinaemia, adjusting for age, sex, and comorbidity. We also analysed low IgA, IgM, and IgG separately. We analysed \"any AED\" exposure and common individual drugs separately. Cumulative exposure data were used to determine whether an exposure-response relationship was present.
RESULTS: 18,666 cases and 127,157 controls were identified. Use of any AED was associated with increased risk of hypogammaglobulinaemia (adjusted odds ratio [aOR] 1.20 [95% CI: 1.15-1.25]). Phenytoin use was strongly associated with low IgA (aOR 5.90 [95% CI: 3.04, 10.43]). Carbamazepine and lamotrigine were also associated with low IgA. Apart from topiramate, which was associated with a non-significant decrease in odds of hypogammaglobulinaemia, there was a consistent increase in odds of hypogammaglobulinaemia across most AEDs studied. Panhypogammaglobulinaemia was associated with any AED use, carbamazepine, lamotrigine, gabapentin, and multiple AED use. There was evidence of an exposure-response relationship between any AED use and any hypogammaglobulinaemia, low IgA, and low IgG. Carbamazepine and probably lamotrigine also had an exposure-response relationship with any hypogammaglobulinaemia.
CONCLUSIONS: AEDs may increase hypogammaglobulinaemia risk. Specific classes of immunoglobulins are differentially affected, and the exposure-response analysis suggests this may be causal. Further work should investigate the clinical impact of these findings. Clinicians should check immunoglobulin levels if unusual or recurrent infections occur in patients treated with AEDs.

This study was undertaken to evaluate how the challenges in the recruitment and retention of participants in clinical trials for focal onset epilepsy have changed over time.
In this systematic analysis of randomized clinical trials of adjunct antiseizure medications for medication-resistant focal onset epilepsy, we evaluated how the numbers of participants, sites, and countries have changed since the first such trial in 1990. We also evaluated the proportion of participants who completed each trial phase and their reasons for early trial exit. We analyzed these trends using mixed effects generalized linear models accounting for the influence of the number of trial sites and trial-specific variability.
The number of participants per site has steadily decreased over decades, with recent trials recruiting fewer than five participants per site (reduction by .16 participants/site/year, p < .0001). Fewer participants also progressed from recruitment to randomization over time (odds ratio = .94/year, p = .014). Concurrently, there has been an increase in the placebo response over time (increase in median percent reduction of .4%/year, p = .02; odds ratio of increase in 50% responder rate of 1.03/year, p = .02), which was not directly associated with the number of sites per trial (p > .20).
This historical analysis highlights the increasing challenges with participant recruitment and retention, as well as increasing placebo response. It serves as a call to action to change clinical trial design to address these challenges.

BACKGROUND: Antiepileptic drugs may cause delirium, and the risk may vary with each drug. However, related studies have provided inconsistent results.
OBJECTIVE: The aim of this study was to investigate whether the use of antiepileptic drugs is a risk factor for delirium development.
METHODS: Using the Japanese Adverse Drug Event Report database, we analysed 573,316 reports pertaining to the period from 2004 to 2020. Reporting odds ratios and 95% confidence intervals of delirium associated with use of antiepileptic drugs were calculated after adjusting for potential confounders. Furthermore, for each antiepileptic drug, we performed an analysis stratified based on older age and benzodiazepine receptor agonist usage.
RESULTS: There were 27,439 reports of antiepileptic drug-related adverse events. Of these, 191 reports were associated with antiepileptic drugs and delirium (crude reporting odds ratio [cROR], 1.66; 95% confidence interval [CI], 1.43-1.93). The use of lacosamide (adjusted reporting odds ratio [aROR], 2.44; 95% CI, 1.24-4.80), lamotrigine (aROR, 1.54; 95% CI, 1.05-2.26), levetiracetam (aROR, 1.91; 95% CI, 1.35-2.71), and valproic acid (aROR, 1.49; 95% CI, 1.16-1.91) was related to a significantly higher reporting odds ratio for delirium, even after adjustment for possible confounding factors. However, when used in combination with benzodiazepine receptor agonists, none of the antiepileptic drugs were found to be associated with delirium.
CONCLUSIONS: Our study\'s findings suggest that antiepileptic drug usage may be associated with delirium development.

UNASSIGNED: This study is designed to assess the pattern of nonadherence, and associated factors among ambulatory patients with epilepsy at Jimma Medical Center, Southwestern Ethiopia, from November 2020 to April 2021.
UNASSIGNED: A hospital-based prospective observational study was employed. A consecutive sampling method was used to recruit study participants. Nonadherence was assessed by the Hill-Bone compliance to the high blood pressure therapy scale. A threshold of 18 scores was used to classify adherence status. Epi-Data manager version 4.6 was used for data entry and all statistical analysis was performed by Statistical Package for Social Science 25.0. Multivariable logistic regression was performed to explore associated factors.
UNASSIGNED: A survey included 334 patients with epilepsy. One hundred twenty-two (36.52%) of the study participants were found to be non-adherent. The factors associated with nonadherence were poor involvement of the patient in the therapeutic decision (adjusted odds ratio = 1.74; 95% confidence interval: 1.04-2.90; p = 0.034), per month income of lesser than1000 Ethiopian birr (adjusted odds ratio = 2.66; 95% confidence interval: 1.03-6.84; p = 0.042), recent seizure episodes (adjusted odds ratio = 1.97; 95% confidence interval: 1.20-3.23; p = 0.007), adverse drug reaction (AOR = 2.13; 95% confidence interval: 1.31-3.47; p = 0.002), and negative medication belief (adjusted odds ratio = 1.28; 95% confidence interval: 1.53-2.25; p = 0.043).
UNASSIGNED: In our setting, the magnitude of nonadherence was substantially high. Hence, providing regular health-related information about the disease and treatment, supplying free antiepileptic drugs, routine assessment of adverse drug reactions, and a multidisciplinary approach involving patients may improve adherence.

Non-adherence to anti-seizure medications (ASMs) is common for adolescents with epilepsy, with potentially devastating consequences. Existing adherence interventions in epilepsy do not meet the unique challenges faced by adolescents. Leveraging social norms capitalizes on the increased importance of peer influence while simultaneously targeting the low motivation levels of many adolescents. The current study examined the feasibility, acceptability, and satisfaction of a social norms adherence intervention in adolescents with epilepsy.
A pilot RCT of a mHealth social norms intervention was conducted with adolescents with epilepsy who demonstrated non-adherence (≤95% adherence) during baseline. Adolescents were randomized to either (1) mHealth social norms (reminders, individualized and social norms adherence feedback) or (2) control (reminders and individualized adherence feedback). Primary outcomes included feasibility, acceptability, and satisfaction. Exploratory outcomes included electronically monitored adherence, seizure severity, and health-related quality of life (HRQOL).
One hundred four adolescents were recruited (53% female; Mage = 15.4 ± 1.4 years; 81% White: Non-Hispanic; 5% Black, 10% Bi/Multiracial; 2% White: Hispanic; 1% Other: Hispanic; 1% Bi/Multiracial-Hispanic). Forty-five percent screen-failed due to high adherence, 16% withdrew, and 38% were randomized to treatment (n = 19) or control (n = 21). Recruitment (75%), retention (78%), and treatment satisfaction were moderately high. Engagement with the intervention was moderate, with 64% of participants engaging with intervention notifications. Exploratory analyses revealed that after controlling for COVID-19 impact, the social norms intervention group maintained higher adherence over time compared to the control group. Small to moderate effect sizes were noted for seizure severity and HRQOL between groups.
This pilot intervention appeared feasible and acceptable. Increases in adherence in the treatment versus control group were modest, but a future larger more adequately powered study is needed to detect effects. Notably, it appeared the COVID pandemic influenced adherence behaviors during our trial.