Anti-seizure medication prescription preferences: a Moroccan multicenter study.

Background: The management of epilepsy is mainly based on antiseizure medications (ASMs). More than 20 ASMs have been introduced in clinical practice, providing a multitude of prescription choices. To date, there are no published data on the trends in ASMs prescriptions in Morocco. Therefore, we conducted a survey among practicing neurologists in seven tertiary referral hospitals in Morocco to study the current ASMs prescription preferences and their modifying factors. Methods: Our descriptive and analytical cross-sectional study was based on a survey sent between January and April 2022 to neurologists practicing in seven tertiary referral hospitals in Morocco. Information regarding the prescription of ASMs was collected using an exploitation form and analyzed using the SPSS version 13 software. Results: Based on questionnaire responses, our results showed that Valproic acid (96.3%) and Lamotrigine (59.8%) were the two most prescribed ASMs for generalized seizure types. For focal seizure types, Carbamazepine (98.8%) and Levetiracetam (34.1%) were the most commonly prescribed drugs, whereas for combined focal and generalized seizure types, the combination of Valproic acid and Carbamazepine (38.55%) was the most prescribed. Phenobarbital was the most commonly prescribed ASM for status epilepticus (40.2%). These prescription preferences were mainly due to seizure types, cost, health insurance coverage, years of experience, and additional epileptology training (p < 0.05). Conclusion: Our results show a shift in the prescription of ASMs in Morocco. Similar to many other countries, valproic acid and carbamazepine are considered the first-line treatments for generalized and focal seizure types. Some factors remain as major challenges in enhancing epilepsy management in Morocco.

Glioma-related epilepsy following low-grade glioma surgery.

Background: Epileptic seizures commonly burden low-grade glioma (LGG) patients and negatively impact quality of life, neurocognition, and general patient health. Anti-seizure medications (ASMs) are used to manage seizures but can result in undesired side effects. Our aim was to report our experience in epilepsy in one of the largest case series of LGG patients (reclassified in accordance with the WHO 2021 classification). Furthermore, we evaluate our postoperative seizure frequency difference between LGG patients who use preoperative ASMs and ones with no ASMs. Methods: Data were retrospectively collected from Salford Royal Hospital electronic records and Neuro-Oncology database from 2006 to 2022. Descriptive statistics were performed for demographic analysis, while multivariable analysis was used to determine postoperative seizure-free outcomes. Results: In total, 257 operations were performed on 206 patients. Postoperatively, 114 patients suffered from seizures, and approximately 45.2% of patients developed seizures at 3-12 months postsurgery, with the odds higher in patients on preoperative ASMs. There was no evidence to suggest a higher postoperative seizure rate in patients undergoing awake craniotomy versus general anesthetic. The extent of resection (EOR) was inversely related to seizure failure, with gross-total resection showing a statistically significant reduction in seizures in comparison to all other surgical resections. Conclusions: In our experience, there is no evidence to suggest a reduced postoperative seizure outcome when prescribing preoperative ASMs. EOR is an independent prognosticator for postoperative seizure failure with all other variables demonstrating nonsignificance. Overall, a larger study can investigate the role of ASMs in LGG in greater detail.

Lamotrigine vs levetiracetam in female patients of childbearing age with juvenile absence epilepsy: A Bayesian reanalysis.

OBJECTIVE: Women of childbearing age with juvenile absence epilepsy (JAE) face treatment challenges due to limited access to safe and effective anti-seizure medications (ASMs). In a previous study we compared the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) in women with idiopathic generalized epilepsy (IGE), highlighting a superiority of LEV in juvenile myoclonic epilepsy. In this study, we specifically reanalyzed, through a Bayesian approach and by expanding the previously published cohort, the comparative effectiveness of these ASMs as initial monotherapy in JAE. METHODS: We conducted a multicenter, retrospective, comparative effectiveness study on women of childbearing age diagnosed with JAE and prescribed LEV or LTG as the initial ASM. Inverse probability treatment weighting (IPTW) Bayesian Cox proportional hazard models were employed to evaluate treatment failure (TF) due to ineffectiveness and ASM retention. The patients' center of provenance and year of prescription were considered as random effect factors. Posterior probabilities and relative log-risk distribution were computed, and the distribution of posterior draws was analyzed to assess the evidence supporting LTG superiority over LEV. RESULTS: Of 123 patients, those treated with LTG (n = 67) demonstrated lower TF and higher ASM retention than those treated with LEV (n = 56), with the IPTW-weighted Bayesian Cox proportional hazards model showing a 99.2% posterior probability of LTG being superior on TF and a 99.5% probability on ASM retention. Additional analyses on ≥50% and ≥75% seizure reduction through IPTW-weighted Bayesian logistic regression largely confirmed these findings, whereas the two ASMs did not show evident differences in terms of seizure freedom. The two ASMs showed comparable safety profiles, with only a minority of patients discontinuing treatment due to side effects. SIGNIFICANCE: Bayesian reanalysis supports LTG as first-line monotherapy for JAE in women of childbearing age, emphasizing the importance of individualized treatment strategies in women with IGE. This study underscores the value of Bayesian methods in refining clinical research and treatment decisions.

Trends in Prevalence and Incidence of Epilepsy and Drug-Resistant Epilepsy in Children: A Nationwide Population-Based Study in Korea.

Population-based data on drug-resistant epilepsy (DRE) are lacking. This retrospective study aimed to determine the prevalence and incidence of pediatric epilepsy and DRE in South Korea using health insurance claims data from the Health Insurance Review and Assessment Service (2013-2022). Epilepsy and DRE prevalence and incidence in children <18 years old were estimated over time and by age and sex. Results showed that the age-standardized prevalence and incidence rates of epilepsy increased. The age-standardized prevalence rate of DRE increased, while the age-standardized incidence rate remained unchanged. The standardized prevalence rate of DRE was 0.26 per 1000 persons, and the average standardized incidence rate of DRE was 0.06 per 1000 persons. The prevalence rate of DRE gradually increased with age, with age 0 demonstrating the highest incidence rate. The prevalence of generalized DRE was the highest across all ages, and incidence was the highest at 0 years. Conversely, the incidence of focal DRE did not change with age. Our study revealed a stable incidence rate of DRE in Korea, despite increased prevalence. DRE incidence was the highest in the first year of life, with the generalized type being the most prevalent.

Padsevonil suppresses seizures without inducing cell death in neonatal rats.

BACKGROUND: Padsevonil (PSL) is a rationally designed anti-seizure medication (ASM) which has overlapping mechanisms of action with the two most common ASMs used for neonatal seizures, phenobarbital (PB) and levetiracetam (LEV). Here we evaluated the anti-seizure properties of PSL across the neonatal and adolescent period in rats in the pentlyenetetrazole (PTZ) induced seizures model. METHODS: Postnatal day (P)7, P14 and P21 Sprague-Dawley rat pups were pre-treated with PSL (1-30 mg/kg), and assessed for seizure latency and severity 30 min later following injection of PTZ. A separate cohort of P7 pups were treated with neonatal ASMs and euthanized 24 h later (on P8) to assess induction of cell death, a feature common to many ASMs when given to P7 rodents. This effect has been extensively reported with PB, but not with LEV. Cell death was assessed by PathoGreen staining. RESULTS: PSL suppressed PTZ-evoked seizures across multiple age groups, particularly at higher doses, without producing increased cell death compared to vehicle. The effects of PSL were particularly notable at suppressing tonic-clonic seizure manifestations (82% of P7 and 100% of P14 and P21 animals were protected from tonic-clonic seizures with the 30 mg/kg dose). CONCLUSIONS: PSL displayed dose-dependent anti-seizure effects in immature rodents in the PTZ model of seizures in immature rats. While many ASMs, including PB, induce cell death in neonatal rats, PSL does not. This suggests that PSL may offer therapeutic benefit and a favorable safety profile for the treatment of neonatal seizures.

Effects of ganaxolone on non-seizure outcomes in CDKL5 Deficiency Disorder: Double-blind placebo-controlled randomized trial.

CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy. Ganaxolone, a neuroactive steroid, reduces the frequency of major motor seizures in children with CDD. This analysis explored the effect of ganaxolone on non-seizure outcomes. Children (2-19 years) with genetically confirmed CDD and ≥ 16 major motor seizures per month were enrolled in a double-blind randomized placebo-controlled trial. Ganaxolone or placebo was administered three times daily for 17 weeks. Behaviour was measured with the Anxiety, Depression and Mood Scale (ADAMS), daytime sleepiness with the Child Health Sleep Questionnaire, and quality of life with the Quality of Life Inventory-Disability (QI-Disability) scale. Scores were compared using ANOVA, adjusted for age, sex, number of anti-seizure mediations, baseline 28-day major motor seizure frequency, baseline developmental skills, and behaviour, sleep or quality of life scores. 101 children with CDD (39 clinical sites, 8 countries) were randomized. Median (IQR) age was 6 (3-10) years, 79.2 % were female, and 50 received ganaxolone. After 17 weeks of treatment, Manic/Hyperactive scores (mean difference 1.27, 95%CI -2.38,-0.16) and Compulsive Behaviour scores (mean difference 0.58, 95%CI -1.14,-0.01) were lower (improved) in the ganaxolone group compared with the placebo group. Daytime sleepiness scores were similar between groups. The total change in QOL score for children in the ganaxolone group was 2.6 points (95%CI -1.74,7.02) higher (improved) than in the placebo group but without statistical significance. Along with better seizure control, children who received ganaxolone had improved behavioural scores in select domains compared to placebo.

Cenobamate: real-world data from a retrospective multicenter study.

BACKGROUND: Clinical trials have shown that cenobamate (CNB) is an efficacious and safe anti-seizure medication (ASM) for drug-resistant focal epilepsy. Here, we analyzed one of the largest real-world cohorts, covering the entire spectrum of epilepsy syndromes, the efficacy and safety of CNB, and resulting changes in concomitant ASMs. METHODS: We conducted a retrospective observational study investigating CNB usage in two German tertiary referral centers between October 2020 and June 2023 with follow-up data up to 27 months of treatment. Our primary outcome was treatment response. Secondary outcomes comprised drug response after 12 and 18 months, seizure freedom rates, CNB dosage and retention, adverse drug reactions (ADRs), and changes in concomitant ASMs. RESULTS: 116 patients received CNB for at least two weeks. At 6 months, 98 patients were eligible for evaluation. Thereof 50% (49/98) were responders with no relevant change at 12 and 18 months. Seizure freedom was achieved in 18.4% (18/98) at 6 months, 16.7% (11/66), and 3.0% (1/33) at 12 and 18 months. The number of previous ASMs did not affect the seizure response rate. Overall, CNB was well-tolerated, however, in 7.7% (9/116), ADRs led to treatment discontinuation. The most frequent changes of concomitant ASMs included the discontinuation or reduction of sodium channel inhibitors, clobazam reduction, and perampanel discontinuation, while brivaracetam doses were usually left unchanged. CONCLUSIONS: CNB proved to be a highly effective and generally well-tolerated ASM in patients with severe drug-resistant epilepsy, comprising a broad array of epilepsy syndromes beyond focal epilepsy.

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.

A Real-World Safety Profile in Neurological, Skin, and Sexual Disorders of Anti-Seizure Medications Using the Pharmacovigilance Database of the Korea Adverse Event Reporting System (KAERS).

(1) Background: The utilization of high-quality evidence regarding the safety of anti-seizure medications (ASMs) is constrained by the absence of standardized reporting. This study aims to examine the safety profile of ASMs using real-world data. (2) Methods: The data were collected from the Korea Adverse Event Reporting System Database (KAERS-DB) between 2012 and 2021. In total, 46,963 adverse drug reaction (ADR)-drug pairs were analyzed. (3) Results: At the system organ class level, the most frequently reported classes for sodium channel blockers (SCBs) were skin (37.9%), neurological (16.7%), and psychiatric disorders (9.7%). For non-SCBs, these were neurological (31.2%), gastrointestinal (22.0%), and psychiatric disorders (18.2%). The most common ADRs induced by SCBs were rash (17.8%), pruritus (8.2%), and dizziness (6.7%). Non-SCBs were associated with dizziness (23.7%), somnolence (13.0%), and nausea (6.3%). Rash, pruritus, and urticaria occurred, on average, two days later with SCBs compared to non-SCBs. Sexual/reproductive disorders were reported at a frequency of 0.23%. SCBs were reported as the cause more frequently than non-SCBs (59.8% vs. 40.2%, Fisher's exact test, p < 0.0001). (4) Conclusions: Based on real-world data, the safety profiles of ASMs were identified. The ADRs induced by SCBs exhibited different patterns when compared to those induced by non-SCBs.

Patient-Centered Management of Brain Tumor-Related Epilepsy.

PURPOSE OF REVIEW: Brain tumor-related epilepsy is a heterogenous syndrome involving variability in incidence, timing, pathophysiology, and clinical risk factors for seizures across different brain tumor pathologies. Seizure risk and disability are dynamic over the course of disease and influenced by tumor-directed treatments, necessitating individualized patient-centered management strategies to optimize quality of life. RECENT FINDINGS: Recent translational findings in diffuse gliomas indicate a dynamic bidirectional relationship between glioma growth and hyperexcitability. Certain non-invasive measures of hyperexcitability are correlated with survival outcomes, however it remains uncertain how to define and measure clinically relevant hyperexcitability serially over time. The extent of resection, timing of pre-operative and/or post-operative seizures, and the likelihood of tumor progression are critical factors impacting the risk of seizure recurrence. Newer anti-seizure medications are generally well-tolerated with similar efficacy in this population, and several rapid-onset seizure rescue agents are in development and available. Seizures in patients with brain tumors are strongly influenced by the underlying tumor biology and treatment. An improved understanding of the interactions between tumor cells and the spectrum of hyperexcitability will facilitate targeted therapies. Multidisciplinary management of seizures should occur with consideration of tumor-directed therapy and prognosis, and anti-seizure medication decision-making tailored to the individual priorities and quality of life of the patient.

Clinical features of unilateral multilobar and hemispheric polymicrogyria (PMG)-related epilepsy and seizure outcome with different treatment options.

OBJECTIVE: To provide evidence for choosing surgical or nonsurgical treatment for epilepsy in patients with unilateral multilobar and hemispheric polymicrogyria (PMG). METHODS: We searched published studies until September 2022 related to unilateral multilobar and hemispheric PMG and included patients who were followed up at the Pediatric Epilepsy Centre of Peking University First Hospital in the past 10 years. We summarized the clinical characteristics and compared the long-term outcomes after surgical or nonsurgical (anti-seizure medications, ASMs) treatment. RESULTS: A total of 70 patients (49 surgical, 21 non-surgical) with unilateral multilobar and hemispheric PMG were included. The median age at epilepsy onset was 2.5 years (1.0-4.1). The most common seizure types were focal and atypical absence seizures. In the whole cohort, 87.3% had hemiparesis and 67.1% had electrical status epilepticus during slow sleep (ESES). There were significant differences in age at epilepsy onset, extent of lesion, and EEG interictal discharges between the two groups. At the last follow-up (median 14.1 years), the rates of seizure-freedom (81.6% vs. 57.1%, p = 0.032) and ASM discontinuation (44.4% vs. 6.3%, p = 0.006) were higher in the surgical group than in the nonsurgical group. Patients in the surgical group had a higher rate of seizure-freedom with complete resection/disconnection than with subtotal resection (87.5% vs. 55.6%, p = 0.078), but with no statistically significant difference. In the nonsurgical group, more extensive lesions were associated with worse seizure outcomes. Cognition improved postoperatively in 90% of surgical patients. SIGNIFICANCE: In patients with unilateral multilobar and hemispheric PMG, the age of seizure onset, the extent of the lesion and EEG features can help determine whether surgery should be performed early. Additionally, surgery could be more favorable for achieving seizure freedom and cognitive improvement sooner. PLAIN LANGUAGE SUMMARY: We aim to summarize clinical characteristics and compare the long-term outcomes after surgical and nonsurgical (ASM) treatment to provide a basis for treatment decisions for patients with unilateral multilobar and hemispheric polymicrogyria (PMG)-related epilepsy. We found that patients with unilateral hemispheric and multilobar PMG had significantly higher rates of seizure freedom and ASM discontinuation with surgical treatment than with nonsurgical treatment. In the surgical group, seizure outcomes were better in patients treated with complete resection/disconnection than in those treated with subtotal resection, but the difference was not statistically significant.

Perampanel in post-stroke epilepsy: Clinical practice data from the PERampanel as Only Concomitant antiseizure medication (PEROC) study.

INTRODUCTION: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy. Nevertheless, there is limited evidence regarding the clinical profile of antiseizure medications (ASMs) in PSE. This study aims to evaluate the 12-month effectiveness and tolerability of perampanel (PER) used as only add-on treatment in patients with PSE in a real-world setting. METHODS: We performed a subgroup analysis of PSE patients included in a previous retrospective, longitudinal, multicentre observational study on adults. Treatment discontinuation, seizure frequency and adverse events were collected at 3, 6 and 12 months. Sub-analyses by early (≤1 previous ASM) or late PER add-on were also conducted. RESULTS: Our analysis included 56 individuals with PSE, characterized by varying initial treatment modalities and timeframes relative to disease onset. We found notable retention rates (92.8%, 83.7%, and 69% at 3, 6, and 12 months), with treatment withdrawal mainly due to poor tolerability. One year after PER introduction, seizure frequency significantly reduced, with a responder rate (≥50% reduction) of 83.9% and a seizure-free rate of 51.6%. Adverse events occurred in 25 (46.3%) patients, mainly dizziness, irritability, and behavioural disorders. No major statistical differences were found between early (30 patients, 53.6%) and late add-on groups, except for a higher 6-month responder rate in the early add-on group. CONCLUSION: Adjunctive PER was effective and well-tolerated in patients with PSE in a real-world setting. Perampanel demonstrated good efficacy and safety as both early and late add-on treatment, making it a compelling option for this unique patient population.

Effectiveness of Highly Purified Cannabidiol in Refractory and Super-Refractory Status Epilepticus: A Case Series.

INTRODUCTION: Refractory and super-refractory status epilepticus are medical emergencies that must be promptly treated in consideration of their high mortality and morbidity rate. Nevertheless, the available evidence of effective treatment of these conditions is scarce. Among novel antiseizure medications (ASMs), highly purified cannabidiol (hpCBD) has shown noteworthy efficacy in reducing seizures in Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). CASE PRESENTATION: Here, we present two cases of effective use of hpCBD in both refractory and super- refractory status epilepticus. The administration of the nasogastric tube permitted the resolution of status epilepticus without adverse events. At 6-month follow-up, both patients were on hpCBD treatment, which continued to be efficacious for treating seizures. CONCLUSION: According to our experience, hpCBD should be taken into consideration as an add-on therapy of RSE and SRSE while also considering the possibility of maintaining this treatment during the follow-up of patients. However, more studies and real-world experiences are needed to better understand its effectiveness in this setting and the interaction with other ASMs.

Treatment odyssey to epilepsy surgery in children with focal cortical dysplasia: Risk factors for delayed surgical intervention.

OBJECTIVE: To elucidate the patient's journey to epilepsy surgery and identify the risk factors contributing to surgical delay in pediatric patients with drug-resistant epilepsy (DRE) due to focal cortical dysplasia (FCD). METHODS: A retrospective review was conducted of 93 pediatric patients who underwent curative epilepsy surgery for FCD between January 2012 and March 2023 at a tertiary epilepsy center. The Odyssey plot demonstrated the treatment process before epilepsy surgery, including key milestones of epilepsy onset, first hospital visit, epilepsy diagnosis, MRI diagnosis, DRE diagnosis, and surgery. The primary outcome was surgical delay; the duration from DRE to surgery. Multivariate linear regression models were used to examine the association between surgical delay and clinical, investigative, and treatment characteristics. RESULTS: The median age at seizure onset was 1.3 years (interquartile range [IQR] 0.14-3.1), and at the time of surgery, it was 6 years (range 1-11). Notably, 46% experienced surgical delays exceeding two years. The Odyssey plot visually highlighted that surgical delay comprised a significant portion of the patient journey. Although most patients underwent MRI before referral, MRI abnormalities were identified before referral only in 39% of the prolonged group, compared to 70% of the non-prolonged group. Multivariate analyses showed that delayed notification of MRI abnormalities, longer duration from epilepsy onset to DRE, older age at onset, number of antiseizure medications tried, and moderate to severe intellectual disability were significantly associated with prolonged surgical delay. CONCLUSION: Pediatric DRE patients with FCD experienced a long journey until surgery. Early and accurate identification of MRI abnormalities is important to minimize surgical delays.

The effects of slow wave sleep characteristics on semantic, episodic, and procedural memory in people with epilepsy.

Slow wave sleep (SWS) is highly relevant for verbal and non-verbal/spatial memory in healthy individuals, but also in people with epilepsy. However, contradictory findings exist regarding the effect of seizures on overnight memory retention, particularly relating to procedural and non-verbal memory, and thorough examination of episodic memory retention with ecologically valid tests is missing. This research explores the interaction of SWS duration with epilepsy-relevant factors, as well as the relation of spectral characteristics of SWS on overnight retention of procedural, verbal, and episodic memory. In an epilepsy monitoring unit, epilepsy patients (N = 40) underwent learning, immediate and 12 h delayed testing of memory retention for a fingertapping task (procedural memory), a word-pair task (verbal memory), and an innovative virtual reality task (episodic memory). We used multiple linear regression to examine the impact of SWS duration, spectral characteristics of SWS, seizure occurrence, medication, depression, seizure type, gender, and epilepsy duration on overnight memory retention. Results indicated that none of the candidate variables significantly predicted overnight changes for procedural memory performance. For verbal memory, the occurrence of tonic-clonic seizures negatively impacted memory retention and higher psychoactive medication load showed a tendency for lower verbal memory retention. Episodic memory was significantly impacted by epilepsy duration, displaying a potential nonlinear impact with a longer duration than 10 years negatively affecting memory performance. Higher drug load of anti-seizure medication was by tendency related to better overnight retention of episodic memory. Contrary to expectations longer SWS duration showed a trend towards decreased episodic memory performance. Analyses on associations between memory types and EEG band power during SWS revealed lower alpha-band power in the frontal right region as significant predictor for better episodic memory retention. In conclusion, this research reveals that memory modalities are not equally affected by important epilepsy factors such as duration of epilepsy and medication, as well as SWS spectral characteristics.

Tolerability of perampanel: A retrospective study at the department of psychiatry.

PURPOSE: We aimed to identify factors that contribute to the discontinuation of perampanel. METHODS: We retrospectively analyzed patients with epilepsy at the Department of Psychiatry, Hokkaido University Hospital. We evaluated the factors contributing to perampanel discontinuation as primary outcomes using Cox proportional hazards regression. Then, we explored the components contributing to the primary outcomes using logistic regression analysis. RESULTS: A total of 118 patients were included, 44.9% of whom discontinued participation, 22.0% had intellectual disability, and 23.7% had a psychiatric disorder other than intellectual disability. Adverse effects occurred in 65% of the patients, 23.7% had psychiatric adverse effects (PAE), and 49.2% had common adverse effects (CAE). The effect of PER to suppress seizures was confirmed in 65.3% of them. Discontinuation was influenced by non-response (Hazard Ratio (HR) 6.70, 95% Confidence Interval (CI) 3.42-13.1), the occurrence of PAE (HR 3.68, 95% CI 1.89-7.16), CAE (HR 1.90, 95% CI 1.06-3.41), and comorbid psychiatric disorders (HR 2.35, 95% CI 1.21-4.59). Moreover, comorbid intellectual disability correlated with a low risk of PAE (OR 0.19, 95% CI 0.04-0.89). CONCLUSION: The discontinuation of perampanel is influenced by poor efficacy and the occurrence of common/psychiatric adverse effects. The discontinuation of perampanel is influenced by poor efficacy and the occurrence of common/psychiatric adverse effects. Consideration of factors contributing to perampanel discontinuation may assist in determining the indication for perampanel treatment.

Impaired executive functioning in children of women with epilepsy.

OBJECTIVE: While neurodevelopmental symptoms are often seen in children of mothers with epilepsy, research specifically addressing executive function (EF) in this population is limited. This study aims to investigate EF in children of mothers with epilepsy, both with and without fetal exposure to anti-seizure medications, compared to typically developing children whose mothers do not have epilepsy. METHODS: We evaluated EF in children aged 8 to 17 years born to mothers with clinically validated diagnoses of epilepsy, using the Behavior Rating Inventory of Executive Function completed by the mothers. The results were then compared to a typically developing control group at the same age living in the same geographic area. RESULTS: The results showed significantly higher levels of EF problems in children of mothers with epilepsy who were exposed (p = 0.005, d = 0.63), and unexposed (p = 0.001, d = 0.74) to anti-seizure medications during pregnancy, compared to typically developing children. There was no significant difference in EF problems between the exposed and unexposed groups. These findings remained statistically significant after adjusting for mothers' education levels, and when excluding participants exposed to valproate during pregnancy. SIGNIFICANCE: This study highlights the increased risk of EF problems in children of mothers with epilepsy, independent of exposure to anti-seizure medications. Findings underscore the importance of continuous monitoring of EF in these children and highlights the need for further research into the diverse factors affecting EF development in this group.

PYRIDOXINE-dependent epilepsy (PDE): An observational study of neonatal cases on the role of pyridoxine in patients treated with standard anti-seizure medications.

BACKGROUND: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE). MATERIALS AND METHODS: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure's onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments. RESULTS: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as "Responder with Relapse", 11 as "Resistant", 6 as "Pyridoxine First Approach", and 2 as "Responders". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up. CONCLUSIONS: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine.

A multicenter, matched case-control analysis comparing burden of illness among patients with tuberous sclerosis complex related epilepsy, generalized idiopathic epilepsy, and focal epilepsy in Germany.

BACKGROUND: Depending on the underlying etiology and epilepsy type, the burden of disease for patients with seizures can vary significantly. This analysis aimed to compare direct and indirect costs and quality of life (QoL) among adults with tuberous sclerosis complex (TSC) related with epilepsy, idiopathic generalized epilepsy (IGE), and focal epilepsy (FE) in Germany. METHODS: Questionnaire responses from 92 patients with TSC and epilepsy were matched by age and gender, with responses from 92 patients with IGE and 92 patients with FE collected in independent studies. Comparisons were made across the main QoL components, direct costs (patient visits, medication usage, medical equipment, diagnostic procedures, ancillary treatments, and transport costs), indirect costs (employment, reduced working hours, missed days), and care level costs. RESULTS: Across all three cohorts, mean total direct costs (TSC: €7602 [median €2620]; IGE: €1919 [median €446], P < 0.001; FE: €2598 [median €892], P < 0.001) and mean total indirect costs due to lost productivity over 3 months (TSC: €7185 [median €11,925]; IGE: €3599 [median €0], P < 0.001; FE: €5082 [median €2981], P = 0.03) were highest among patients with TSC. The proportion of patients with TSC who were unemployed (60%) was significantly larger than the proportions of patients with IGE (23%, P < 0.001) or FE (34%, P = P < 0.001) who were unemployed. Index scores for the EuroQuol Scale with 5 dimensions and 3 levels were significantly lower for patients with TSC (time-trade-off [TTO]: 0.705, visual analog scale [VAS]: 0.577) than for patients with IGE (TTO: 0.897, VAS: 0.813; P < 0.001) or FE (TTO: 0.879, VAS: 0.769; P < 0.001). Revised Epilepsy Stigma Scale scores were also significantly higher for patients with TSC (3.97) than for patients with IGE (1.48, P < 0.001) or FE (2.45, P < 0.001). Overall Quality of Life in Epilepsy Inventory-31 items scores was significantly lower among patients with TSC (57.7) and FE (57.6) than among patients with IGE (66.6, P = 0.004 in both comparisons). Significant differences between patients with TSC and IGE were also determined for Neurological Disorder Depression Inventory for Epilepsy (TSC: 13.1; IGE: 11.2, P = 0.009) and Liverpool Adverse Events Profile scores (TSC: 42.7; IGE: 37.5, P = 0.017) with higher score and worse results for TSC patients in both questionnaires. CONCLUSIONS: This study is the first to compare patients with TSC, IGE, and FE in Germany and underlines the excessive QoL burden and both direct and indirect cost burdens experienced by patients with TSC.

Relationship between depression and sex steroid hormone among women with epilepsy.

Introduction: Sex steroid hormones are emerging significant biomarkers of depression among Women with Epilepsy (WWE) with promising prognostic potential and therapeutic end point. Therefore, the study is aimed at exploring the association between sex steroids hormones, Anti-seizure Medication (ASM) and depression among WWE. Methodology: A baseline questionnaire was used to obtain socio-demographics and clinical characteristic from one hundred and twelve (112) WWE and 50 age matched healthy control. The diagnosis of epilepsy and Electroencephalography (EEG) description was based on 2017 International League Against Epilepsy (ILAE) criteria. Blood samples were collected from cases and control during Luteal Phase (LP) and Follicular Phase (FP). The Zung Self-Rating Depression Scale (ZSRDS) was used to assess depression. Result: The prevalence of depression among WWE is 18.8%, with a significant difference between the level of formal education (p0.000), age (p0.000), and mean ZSRDS (p0.000) among cases and control. There is a statistical difference in hormonal levels between cases and control with regards to higher testosterone [3.28 ± 9.99 vs. 0.31 ± 0.30; p0.037], lower FP prolactin [16.37 ± 20.14 vs. 17.20 ± 7.44; p0.778], and lower LP prolactin [15.74 ± 18.22 vs. 17.67 ± 7.27; p0.473]. Testosterone (p0.024), FP Follicle Stimulating Hormone (FSH) (p0.009), FP Estradiol (p0.006), LP FSH (p0.031), LP Progesterone (p0.023), and LP Prolactin (p0.000) were associated with depression. However, only prolactin (p0.042) and testosterone (p0.000) predicts depression among WWE. Conclusion: There was higher mean depression score, lower prolactin and higher testosterone level among cases compared to control. Furthermore, there was lower prolactin and higher testosterone level in Carbamazepine (CBZ) group compared to Levetiracetam (LEV) groups.