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Background: Anti-seizure medications (ASMs) are the primary therapeutic mode to control seizures in patients with epilepsy. Adherence to the medications is critical to achieving the goals of epilepsy therapy. However, the cost of the medications and the interrupted availability of ASMs contribute to non-adherence to epilepsy treatment. Therefore, this study aimed to assess ASM adherence and its association with self-reported medication availability and affordability. Objective: To assess whether self-reported availability and affordability of Anti-seizure medications affect medication adherence among Epileptic Patients at Eka Kotebe General Hospital, Addis Ababa, Ethiopia, from January 13, 2023 to March 23, 2023. Methods: A hospital-based analytical cross-sectional study was conducted among 357 epileptic patients using the Consecutive sampling method in Eka Kotebe General Hospital, Addis Ababa, Ethiopia. ASM adherence was measured using a self-report 3items questionnaire focusing on medication use patterns of patients from their last visit to the current visit. Statistical packages for Social Sciences 26.0 version statistical software cleaned, coded and analyzed the collected data. Binary logistic regression was fitted, and P-values less than 0.05 were considered to have statistical significance. Result: The prevalence of ASM adherence was 55.2% with 95% CI (50.1%; 60.2%). About two-thirds (61.3%) of patients in this study had limited access to the ASMs or could not afford the medications. Self-reported availability of ASMs (AOR = 2.01, 95% CI = 1.01, 3.98) was significantly associated with ASM adherence. Self-reported affordability of ASMs was associated with ASM adherence in the Bivariate logistic regression analysis; however, when adjusted for other covariates in the multivariable logistic regression, no significant association was observed (p = 0.674). Conclusion and recommendation: Only about half of the epileptic patients adhered to ASMs at Eka Kotebe General Hospital. Self-reported availability of ASMs was an essential factor. Improving access to ASMs is critical to improving adherence and management of epilepsy. [ABSTRACT FROM AUTHOR]

The aim of this study was to report the translation into Romanian of the Seizure Severity Questionnaire (SSQ), an instrument for the evaluation of the frequency and severity of epileptic seizures, and the results of applying it to a group of patients with epilepsy evaluated at a hospital in Romania. Methods: Four translators were involved in obtaining conceptual analogies and the cultural importance of the translated notions. The final version was obtained for the Romanian population, with the same appearance as the original instrument. Sixty-seven patients with epilepsy completed the SSQ and the Patient-Weighted Quality of Life in Epilepsy Inventory—QOLIE-31-P. Results: Females had a lower mean SSQ total score (TS) and perceived seizures less seriously than men. Patients with epilepsy with aura had a higher mean SSQ TS, with a more severe seizure perception, compared to those without aura. According to the frequency of seizures, patients with epilepsy with rare seizures had the lowest mean SSQ total score (TS) compared to those with frequent seizures. Patients who were on monotherapy had a less severe perception of epileptic seizures compared to those who were treated with two or more antiepileptic drugs. All QOLIE-31-P domains and TS correlated statistically significantly with the SSQ TS. Conclusions: This study explored SSQ translation, evaluated preliminary results, and showed the correlation between seizure frequency and severity, clinical factors, and quality of life. This tool could be useful for measuring seizure severity in Romanian patients with epilepsy and conducting comparative studies. [ABSTRACT FROM AUTHOR]

Objective: To explore the presence of drug dependence and Epilepsy in patients with PTC (Post Truamatic Contusions) balanced cautiously. Study Design: Proposed Reviewed Research study. Setting: Hayatabad Medical Complex, Peshawar. Period: July 2020 to December 2020. Methods: About 90% of patients aged between fifteen to sixtyfive years old identified with cerebral lesion and balanced cautiously were applied. Follow up sessions was provided to patients for 12to 18 months. Results: Among the enrolled patients, 23% established early PTS (Post Traumatic Seizures) and approximately established late PTS (Post Traumatic Seizures) from mild to moderate level of cerebral lesion. Patients having early signs of Post traumatic Seizure, about 6% utilized AEDs (Anti-epileptic Drugs) for about 3 months throughout the treatment period and about 7% of patients along with late Post Traumatic Seizures utilized AEDs. Moreover, approximately 8 percent patients established late post traumatic Seizure without considering any early signs of condition. Research findings indicated that only 3% of patients with early and late PTS actually required AEDs for at least 6 months. Although, about 44 percent of patients were utilizing Anti-epileptic drugs to control seizures. Sensible usage of Anti-epileptic drugs is familiar in our region, contributing to enhanced danger of medicine opposition and acquiring financial pressure on low-paid people in well-established state. Additionally, extreme usage of anti-epileptic and prophylactic drugs doesn't impact the occurrence of PTE (Post Traumatic Epilepsy). Conclusion: The presence of late and early post-traumatic epilepsy observed within our study is contrast to that explored in another research. Sensible production of AEDs is occured in our state, that increases the danger of medicine opposition and attain financial issues for economically destruct people in well-established states. Extreme usage of AEDs and prophylactic drugs doesn't have an important influence on stopping PTE. [ABSTRACT FROM AUTHOR]

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

Objective Methods Results Significance Sudden unexpected death in epilepsy (SUDEP) results in more years of potential life lost than any neurological condition with the exception of stroke. It is generally agreed that SUDEP happens due to some form of respiratory, cardiac, and electrocerebral dysfunction following a seizure; however, the mechanistic cause of these perturbations is unclear. One possible explanation lies with adenosinergic signaling. Extracellular levels of the inhibitory neuromodulator adenosine rapidly rise during seizures, a countermeasure that is necessary for seizure termination. Previous evidence has suggested that excessive adenosinergic inhibition could increase the risk of SUDEP by silencing brain areas necessary for life, such as the respiratory nuclei of the brainstem. The goal of this investigation was to further clarify the role of adenosine in seizure‐induced respiratory and electrocerebral dysfunction.To determine the role of adenosine in postictal physiological dysregulation, we pharmacologically manipulated adenosine signaling prior to amygdala‐kindled seizures in mice while recording electroencephalogram (EEG), electromyogram, and breathing using whole body plethysmography. The adenosinergic drugs used in this study included selective and nonselective adenosine receptor antagonists and inhibitors of adenosine metabolism.We found that high doses of adenosine receptor antagonists caused some seizures to result in seizure‐induced death; however, counterintuitively, animals in these conditions that did not experience seizure‐induced death had little or no postictal generalized EEG suppression. Inhibitors of adenosine metabolism had no effect on postictal breathing but did worsen some postictal electrocerebral outcomes.The unexpected effect of high doses of adenosine antagonists on seizure‐induced death observed in this study may be due to the increase in seizure severity, vasoconstriction, or phosphodiesterase inhibition caused by these drugs at high doses. These findings further clarify the role of adenosine in seizure‐induced death and may have implications for the consumption of caffeine in epilepsy patients and the prevention of SUDEP. [ABSTRACT FROM AUTHOR]

Epilepsy affects over 65 million people worldwide. One-third of people with epilepsy do not respond to medication and may benefit from surgery. Vagus nerve stimulation (VNS) is the first neuromodulation therapy for the treatment of drug-resistant epilepsy. This method is used in combination with anti-seizure medications in adults and in the pediatric population. VNS has also been demonstrated to have benefits for some epilepsy comorbidities, such as depression, and can be used in combination with other neuromodulation therapies in epilepsy. The authors present an overview of VNS physiology, patient selection, surgery and risks, neuromodulation therapy, and application to epilepsy comorbidities. [ABSTRACT FROM AUTHOR]

Background: Carbamazepine (CBZ) is a first-choice anti-seizure medication (ASM) whose efficacy is often invalidated by adverse effects (AEs). Eslicarbazepine (ESL) is a structural derivative of CBZ with better pharmacokinetic/tolerability profiles. We describe our experience of the overnight CBZ to ESL switch in people with epilepsy (PwE) to improve seizure control, AEs, and ASMs adherence. Methods: We retrospectively included 19 PwE (12 females, 53 ± 21 years old) who underwent CBZ to ESL overnight switch due to single/multiple issues: poor efficacy (pEff, N = 8, 42%), tolerability (pToll, N = 11, 58%), adherence (pAdh, N = 2, 10%). 9/19 (47%) had psychiatric comorbidities. Clinical variables, seizure frequency, and AEs were recorded at switch time (T0) after 3.5 ± 3 (T1) and 6.5 ± 1.5 months (T2). Results: At T1, in pEff group, 1/8 (13%) was seizure free, 2/8 (25%) were responders (> 50% seizure reduction), 2/8 (25%) had no seizure changes, 3/8 (37%) had seizure worsening; the latter were those with the most severe epilepsy and encephalopathy. In pToll group, all PwE experienced AEs disappearance/amelioration. In pAdh group, all PwE reported adherence amelioration. Four dropouts. At T2, no changes were recorded within groups, while in the whole sample, 6/15 (40%) were responders, and 4/15 (27%) were seizure-free. No one complained of Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation psychiatric worsening, while 6/19 (32%) experienced mood/behavior benefits. Conclusions: CBZ to ESL overnight switch offers an opportunity to improve efficacy, tolerability, adherence, and psychiatric symptoms. [ABSTRACT FROM AUTHOR]

Objectives: Pathological forms of neural activity, such as epileptic seizures, modify the expression pattern of multiple proteins, leading to persistent changes in brain function. One such protein is activity‐regulated cytoskeleton‐associated protein (Arc), which is critically involved in protein‐synthesis–dependent synaptic plasticity underlying learning and memory. In the present study, we have investigated how the expression of ArcKR, a form of Arc in which the ubiquitination sites have been mutated, resulting in slowed Arc degradation, modifies group I metabotropic glutamate receptor–mediated long‐term depression (G1‐mGluR‐LTD) following seizures. Methods: We used a knock‐in mice line that express ArcKR and two hyperexcitation models: an in vitro model, where hippocampal slices were exposed to zero Mg2+, 6 mM K+; and an in vivo model, where kainic acid was injected unilaterally into the hippocampus. In both models, field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 region of hippocampal slices in response to Schaffer collateral stimulation and G1‐mGluR‐LTD was induced chemically with the group 1 mGluR agonist DHPG. Results: In the in vitro model, ArcKR expression enhanced the effects of seizure activity and increased the magnitude of G1‐mGluR LTD, an effect that could be blocked with the mGluR5 antagonist MTEP. In the in vivo model, fEPSPs were significantly smaller in slices from ArcKR mice and were less contaminated by population spikes. In this model, the amount of G1‐mGluR‐LTD was significantly less in epileptic slices from ArcKR mice as compared to wildtype (WT) mice. Significance: We have shown that expression of ArcKR, a form of Arc in which degradation is reduced, significantly modulates the magnitude of G1‐mGluR‐LTD following epileptic seizures. However, the effect of ArcKR on LTD depends on the epileptic model used, with enhancement of LTD in an in vitro model and a reduction in the kainate mouse model. [ABSTRACT FROM AUTHOR]

ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic–clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12 mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8 weeks and 32 (59.3%) patients completed the study. Retention rate at 12 months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy. [ABSTRACT FROM AUTHOR]

Objectives: An important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly using linear methods, e.g., spectral power and individual alpha frequency peak (IAF). However, brain activity is complex and non-linear, hence there is a need to explore EEG neurodynamics using nonlinear approaches. Here, we use the Fractal Dimension (FD), a measure of whole brain signal complexity, to measure the response to anti-seizure therapy in patients with Focal Epilepsy (FE) and compare it with linear methods. Materials: Twenty-five drug-responder (DR) patients with focal epilepsy were studied before (t1, named DR-t1) and after (t2, named DR-t2) the introduction of the anti-seizure medications (ASMs). DR-t1 and DR-t2 EEG results were compared against 40 age-matched healthy controls (HC). Methods: EEG data were investigated from two different angles: frequency domain—spectral properties in δ, θ, α, β, and γ bands and the IAF peak, and time-domain—FD as a signature of the nonlinear complexity of the EEG signals. Those features were compared among the three groups. Results: The δ power differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p  <  0.01 and DR-t2 vs. HC, p  <  0.01). The θ power differed between DR-t1 and DR-t2 (p  =  0.015) and between DR-t1 and HC (p  =  0.01). The α power, similar to the δ, differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p  <  0.01 and DR-t2 vs. HC, p  <  0.01). The IAF value was lower for DR-t1 than DR-t2 (p  =  0.048) and HC (p  =  0.042). The FD value was lower in DR-t1 than in DR-t2 (p  =  0.015) and HC (p  =  0.011). Finally, Bayes Factor analysis showed that FD was 195 times more likely to separate DR-t1 from DR-t2 than IAF and 231 times than θ. Discussion: FD measured in baseline EEG signals is a non-linear brain measure of complexity more sensitive than EEG power or IAF in detecting a response to ASMs. This likely reflects the non-oscillatory nature of neural activity, which FD better describes. Conclusion: Our work suggests that FD is a promising measure to monitor the response to ASMs in FE. [ABSTRACT FROM AUTHOR]

Introduction: Long-term electroencephalography (EEG) monitoring is advised to patients with refractory epilepsy who have a failure of anti-seizure medication and therapy. However, its real-life application is limited mainly due to the use of multiple EEG channels. We proposed a patient-specific deep learningbased single-channel seizure detection approach using the long-term scalp EEG recordings of the Children's Hospital Boston-Massachusetts Institute of Technology (CHB-MIT) dataset, in conjunction with neurologists' confirmation of spatial seizure characteristics of individual patients. Methods: We constructed 18-, 4-, and single-channel seizure detectors for 13 patients. Neurologists selected a specific channel among four channels, two close to the behind-the-ear and two at the forehead for each patient, after reviewing the patient's distinctive seizure locations with seizure re-annotation. Results: Our multi- and single-channel detectors achieved an average sensitivity of 97.05-100%, false alarm rate of 0.22-0.40/h, and latency of 2.1-3.4 s for identification of seizures in continuous EEG recordings. The results demonstrated that seizure detection performance of our single-channel approach was comparable to that of our multi-channel ones. Discussion: We suggest that our single-channel approach in conjunction with clinical designation of the most prominent seizure locations has a high potential for wearable seizure detection on long-term EEG recordings for patients with refractory epilepsy. [ABSTRACT FROM AUTHOR]

Objective The aim was to examine the effect of polytherapy (i.e. the number of administered anti-seizure medications (ASMs)) on memory, and whether the interaction between the number of ASMs and attentional/executive functioning affect presurgical memory functioning and postsurgical memory changes in patients with drug-resistant epilepsy. Methods Two studies were carried out. Study 1 consisted of a presurgical assessment of 125 adult patients, in which attention/executive function (EpiTrack screening tool) and memory were assessed (cross-sectional study). Of them, 72 patients underwent a second postsurgical evaluation, in which memory was assessed (Study 2). Patients were distributed into groups based on EpiTrack performance and number of ASMs. Results The interaction between the number of ASMs and the attentional/executive functioning significantly affected presurgical memory, with patients with impaired EpiTrack performance taking three-four ASMs having poorer scores than patients with intact EpiTrack performance taking three-four ASMs (for all, p  < .0001). This interaction also affected postsurgical memory changes, with patients with impaired Epitrack performance taking three-four ASMs having higher postsurgical decline than those with intact Epitrack performance taking three-four ASMs (for all, p  < .005). No differences were found in patients taking two ASMs. Furthermore, the number of ASMs was associated with presurgical memory performance and postsurgical memory changes only in patients with impaired EpiTrack performance (for all, p  < .05). Conclusions Our findings underline the utility of EpiTrack, together with the clinical information on the number of prescribed ASMs, to corroborate the impact of polytherapy on memory and to optimize the prediction of postsurgical memory changes. [ABSTRACT FROM AUTHOR]

Objective: To gather and assess current literature on the prevalence and efficacy of lifestyle behavioral interventions (sleep, nutrition, physical activity) for health outcomes, including QOL, psychological well-being, behavioral changes, and seizure frequency, among PWE. Data Source: A review was conducted of English-language articles identified from PubMed, Scopus, and Embase between January 2013 to January 2023. Study Inclusion and Exclusion Criteria: Inclusion criteria were randomized controlled trials (RCT) with human subjects diagnosed with epilepsy who participated in a lifestyle behavioral intervention. Data Extraction: Two researchers independently completed the title, abstract, and full-text reviews. Information extracted includes study population, duration, type of intervention, findings, and outcomes. Data Synthesis: Data was narratively synthesized to show level of evidence and degree of consistency in findings. Results: 4001 studies identified, 66 full texts reviewed, and 24 included. A majority (n = 16) of studies utilized diet specific RCTs, and some focused on physical activity (n = 7) and sleep (n = 1). Diet-specific RCTs (eg, ketogenic, Modified Atkins) reported reduced seizure frequency with adverse effects, such as gastrointestinal complications. Physical activity-based interventions found that maintained levels of exercise improved QOL and psychological well-being. However, physical activity and diet-based interventions did not have lasting effects after study conclusion. Only the behavioral sleep intervention reported that sleep quality improved significantly and was maintained post-intervention. Conclusion: Future research is needed to establish the relationship between lifestyle behavioral interventions on QOL and other health outcomes (eg, seizure frequency). [ABSTRACT FROM AUTHOR]

Objective: ESPRITE (Study 508; NCT03836924) evaluated the real‐world safety, tolerability, and efficacy of adjunctive perampanel in patients aged ≥12 years with focal‐onset seizures (FOS), with or without focal to bilateral tonic–clonic seizures (FBTCS), in India. Methods: ESPRITE was a prospective, multicenter, single‐arm, observational, Phase IV study with a 6‐month Treatment Period. Patients were aged ≥12 years and had been prescribed perampanel for adjunctive treatment of FOS, with or without FBTCS. Assessments included incidence of treatment‐emergent adverse events (TEAEs; primary endpoint), median percent reduction in seizure frequency per 28 days from baseline, 50% responder rates, and seizure‐freedom rates. Results: Overall, 200 patients were enrolled (199 patients in the Safety Analysis Set and 174 patients who completed all visits in the main efficacy analyses). TEAEs (all mild or moderate in severity) were reported in 18.1% (n = 36/199) of patients (the most common were dizziness [3.0%] and irritability [2.0%]). TEAEs leading to discontinuation of perampanel were reported in 2.0% of patients; no deaths or serious TEAEs occurred. At 6 months, median percent reduction in seizure frequency was 100.0%, 50% responder rate was 83.3%, and seizure‐freedom rate was 49.4%. Significance: Adjunctive perampanel (at a mean daily dose of 4 mg/day) was shown to be well tolerated and effective in patients aged ≥12 years with FOS, with or without FBTCS, from India. Plain Language Summary: Many patients do not receive adequate treatment for epilepsy and need effective seizure control medications. In this 6‐month clinical study, 199 patients from India, aged 12 years or older, added perampanel to the anti‐seizure medications they were already taking. At 6 months, 49% of patients experienced no seizures since starting perampanel and seizure frequency was reduced by half in 83% of patients. Side effects occurred in 18% of patients (most commonly dizziness and irritability) and caused 2% to stop perampanel; no deaths were reported. Perampanel was an effective and generally safe added medication for patients with epilepsy from India. [ABSTRACT FROM AUTHOR]

Objective: To report the interim results of the PERPRISE study (Study 509; NCT04202159), which is evaluating perampanel as the only adjunctive anti‐seizure medication (ASM) in adults with focal to bilateral tonic–clonic seizures (FBTCS) or primary generalized tonic–clonic seizures (GTCS). Methods: PERPRISE is an ongoing 12‐month multicenter, prospective, observational, non‐interventional study of perampanel in a real‐world setting in Germany. Patients are aged ≥18 years with FBTCS or GTCS due to focal or idiopathic generalized epilepsy. Perampanel, as an adjunctive therapy to ASM monotherapy ('add‐on therapy') or as a substitute for one ASM in dual therapy ('substitution therapy'), is prescribed in line with its SmPC. The Interim Analysis Set comprises the first 100 patients who received ≥1 dose of perampanel and attended or discontinued prior to the ~6‐month visit. Interim endpoints include retention rate, measures of effects on seizure frequency, and treatment‐emergent adverse events (TEAEs). Results: One hundred patients were included in the Interim Analysis Set (add‐on, n = 43 [43.0%]; substitution, n = 55 [55.0%]; unknown, n = 2). The 6‐month retention rate was 78.0% (add‐on, 83.7%; substitution, 72.7%). For the overall population with GTCS and/or FBTCS, seizure‐freedom rate at 6 months was 58.8% (add‐on, 72.2%; substitution, 47.9%) and 50% responder rate at 6 months was 82.6% (add‐on, 89.2%; substitution, 76.6%). Retention rates and seizure outcomes were better with perampanel as an early‐line treatment than as a late‐line treatment. TEAEs were reported by 48 patients (48.0%), most commonly dizziness (n = 9), fatigue (n = 7), and irritability (n = 7). Sixteen patients (16.0%) withdrew from perampanel treatment due to TEAEs. Significance: The interim analysis of PERPRISE offers insight into the real‐world use of perampanel in Germany, including for the first time, clinical practice data from patients with GTCS and switching ASMs within a dual therapy. Further data from PERPRISE will be of value to inform clinical decision‐making in this patient cohort. Plain Language Summary: Patients with epilepsy often take more than one medication for seizure control. This 12month study looked at patients in Germany receiving perampanel as only add‐on medication. The interim analysis shows, that at 6 months, over 70% of the 100 patients continued to use perampanel; 59% experienced no seizures during treatment with perampanel, and in 83%, seizure frequency was reduced by half. Side effects occurred in 48% of patients (most commonly dizziness, fatigue, and irritability) and caused 16% to withdraw from the study. Overall, perampanel was a suitable as only add‐on medication for patients with epilepsy. [ABSTRACT FROM AUTHOR]

Although Coronavirus disease 2019 (COVID-19) vaccinations are generally recommended for persons with epilepsy (PwE), a significant vaccination gap remains due to patient concerns over the risk of post-vaccination seizure aggravation (PVSA). In this single-centre, retrospective cohort study, we aimed to determine the early (7-day) and delayed (30-day) risk of PVSA, and to identify clinical predictors of PVSA among PwE. Adult epilepsy patients aged ≥18 years without a history of COVID-19 infection were recruited from a specialty epilepsy clinic in early 2022. Demographic, epilepsy characteristics, and vaccination data were extracted from a centralized electronic patient record. Seizure frequency before and after vaccination, vaccination-related adverse effects, and reasons for or against vaccination were obtained by a structured questionnaire. A total of 786 PwEs were included, of which 27.0% were drug-resistant. At the time of recruitment, 74.6% had at least 1 dose of the COVID-19 vaccine. Subjects with higher seizure frequency (p < 0.0005), on more anti-seizure medications (p = 0.004), or had drug-resistant epilepsy (p = 0.001) were less likely to be vaccinated. No significant increase in seizure frequency was observed in the early (7 days) and delayed phases (30 days) after vaccination in our cohort. On the contrary, there was an overall significant reduction in seizure frequency 30 days after vaccination (1.31 vs. 1.89, t = 3.436; p = 0.001). This difference was seen in both types of vaccine (BNT162b2 and CoronaVac) and drug-resistant epilepsy, but just missed significance for the second dose (1.13 vs. 1.87, t = 1.921; p = 0.055). Only 5.3% had PVSA after either dose of vaccine. Higher pre-vaccination seizure frequency of ≥1 per week (OR 3.01, 95% CI 1.05–8.62; p = 0.04) and drug-resistant status (OR 3.32, 95% CI 1.45–249 7.61; p = 0.005) were predictive of PVSA. Meanwhile, seizure freedom for 3 months before vaccination was independently associated with a lower risk of PVSA (OR 0.11, 95% CI 0.04–0.28; p < 0.0005). This may guide epilepsy treatment strategies to achieve better seizure control for at least 3 months prior to vaccination. As COVID-19 shifts to an endemic phase, this study provides important data demonstrating the overall safety of COVID-19 vaccinations among PwE. Identification of high-risk patients with subsequent individualized approaches in treatment and monitoring strategies may alleviate vaccination hesitancy among PwE. [ABSTRACT FROM AUTHOR]

This article discusses the successful use of cannabidiol (CBD) in the treatment of nonconvulsive status epilepticus (NCSE) in a patient with Angelman syndrome (AS). AS is a rare neurogenetic disorder characterized by developmental delay, seizures, cognitive impairment, and motor dysfunction. NCSE is a common complication in AS, and treatment options are limited. The patient in this case study was treated with Epidyolex® CBD, which resulted in improved responsiveness, seizure freedom, and significant improvement in EEG abnormalities. The use of CBD in refractory status epilepticus has shown favorable outcomes in previous studies. While this case study is anecdotal, it suggests that CBD may be a promising treatment for NCSE in AS and warrants further research and clinical trials. [Extracted from the article]

Background: Epilepsy, a chronic brain disorder characterized by abnormal brain activity that causes seizures and other symptoms, is typically treated using anti-epileptic drugs (AEDs) as the first-line therapy. However, due to the variations in their modes of action, identification of effective AEDs often relies on ad hoc trials, which is particularly challenging for pediatric patients. Thus, there is significant value in computational methods capable of assisting in the selection of AEDs, aiming to minimize unnecessary medication and improve treatment efficacy. Results: In this study, we collected 7,507 medical records from 1,000 pediatric epilepsy patients and developed a computational clinical decision-supporting system for AED selection. This system leverages three multi-channel convolutional neural network (CNN) models tailored to three specific AEDs (vigabatrin, prednisolone, and clobazam). Each CNN model predicts whether a respective AED is effective on a given patient or not. The CNN models showed AUROCs of 0.90, 0.80, and 0.92 in 10-fold cross-validation, respectively. Evaluation on a hold-out test dataset further revealed positive predictive values (PPVs) of 0.92, 0.97, and 0.91 for the three respective CNN models, representing that suggested AEDs by our models would be effective in controlling epilepsy with a high accuracy and thereby reducing unnecessary medications for pediatric patients. Conclusion: Our CNN models in the system demonstrated high PPVs for the three AEDs, which signifies the potential of our approach to support the clinical decision-making by assisting doctors in recommending effective AEDs within the three AEDs for patients based on their medical history. This would result in a reduction in the number of unnecessary ad hoc attempts to find an effective AED for pediatric epilepsy patients. [ABSTRACT FROM AUTHOR]

Background and objective: Epilepsy is a prevalent neurological disorder that affects a significant number of individuals globally. This condition is associated with a high occurrence of psychiatric comorbidities, which can significantly affect the quality of life of individuals affected. The aim of this study was to investigate the association between antiseizure therapies and the likelihood of psychiatric comorbidities in individuals with epilepsy. Methodology: Data for this study was gathered from the Neurology referral center in Islamabad, Pakistan. A standardized questionnaire was utilized to gather data from 120 individuals diagnosed with epilepsy. The survey consisted of inquiries regarding the management of seizures, the utilization of anti-seizure medications, and the presence of psychiatric comorbidities. The data was analyzed using the Statistical Package for the Social Sciences (SPSS). Results: The findings indicated that individuals who were using multiple antiseizure medications had a notably higher likelihood of having psychiatric comorbidities in comparison to those who were on mono therapy (p = 0.010). suggests that patients with unsuccessful seizure control are more probable to have psychiatric comorbidities as compared to those with good seizure control (p = 0.029). Conclusion: To conclude poor seizure control and poly therapy are associated with increased risk of psychiatric comorbidities. [ABSTRACT FROM AUTHOR]

The majority of people with epilepsy achieves long-term seizure-freedom and may consider withdrawal of their anti-seizure medications (ASMs). Withdrawal of ASMs can yield substantial benefits but may be associated with potential risks. This review critically examines the existing literature on ASM withdrawal, emphasizing evidence-based recommendations, where available. Our focus encompasses deprescribing strategies for individuals who have attained seizure freedom through medical treatment, those who have undergone successful epilepsy surgery, and individuals initiated on ASMs following acute symptomatic seizures. We explore state-of-the-art prognostic models in these scenarios that could guide the decision-making process. The review underscores the importance of a collaborative shared-decision approach between patients, caregivers, and physicians. We describe the subjective and objective factors influencing these decisions and illustrate how trade-offs may be effectively managed in practice. [ABSTRACT FROM AUTHOR]

Background: A third of people with epilepsy are drug resistant. People with drug-resistant epilepsy (DRE) have a higher risk of mortality and physical injuries than those who respond to anti-seizure medication (ASM). This study describes patient characteristics, comorbidities, and mortality in people with DRE in the UK. Methods: The Clinical Practice Research Datalink was utilised to select people with DRE prescribed a third ASM between 1 January 2011 and 31 March 2021. Annual incidence and prevalence of DRE, patient characteristics, comorbidities, and mortality rates were analysed. Subgroup analysis was performed by age, sex, presence of intellectual disabilities and time from epilepsy diagnosis to DRE. Results: A total of 34,647 people with DRE were included (mean ± SD age 42.68 ± 23.59 years, 52.6% females). During the study period, annual DRE incidence ranged from 1.99% to 3.12%. As of 31 March 2021, DRE prevalence was 26.6% (95% confidence interval [CI] 26.3%–26.8%). A greater proportion of people with DRE resided in the most deprived regions, with 21.1% and 16.7% in the top two quintiles of the Index of Multiple Deprivation respectively, compared to < 15% in the three less deprived regions. All-cause mortality ranged from 3,687 to 4,802 per 100,000 persons with DRE, four times higher than that in the general population in the UK. Variations existed across subgroups. Conclusions: Considerable disease burden was observed in people with DRE in the UK. The findings emphasise the importance of early DRE diagnosis and appropriate disease management in people who develop DRE. [ABSTRACT FROM AUTHOR]

Epilepsy is associated with increased mortality. Cardiovascular disease confers a significant portion of this increased risk. Recently there is increased interest in the burden of cardiovascular mortality in people with epilepsy. This review discusses themost common cardiovascular risk factors and their association with epilepsy including obesity, diabetes mellitus, and hyperlipidemia. Hyperlipidemia related to the use of enzyme inducing anti-seizure medications is also discussed as a topic that is of particular importance to prescribers that have patients with comorbid cardiovascular risk and epilepsy. Heart rate variability (HRV) and its association with SUDEP is discussed as well as a contributor to vascular risk. Finally, the authors discuss a potential role for neurologists who treat epilepsy to engage closer with their patient's cardiovascular risk factors using available tools such as a the ASCVD score calculator to determine the overall risk ofmortality, as well as acting upon this information to guide treatment approaches integrating the information provided in this review. [ABSTRACT FROM AUTHOR]

The intricate relationship between viruses and epilepsy involves a bidirectional interaction. Certain viruses can induce epilepsy by infecting the brain, leading to inflammation, damage, or abnormal electrical activity. Conversely, epilepsy patients may be more susceptible to viral infections due to factors, such as compromised immune systems, anticonvulsant drugs, or surgical interventions. Neuroinflammation, a common factor in both scenarios, exhibits onset, duration, intensity, and consequence variations. It can modulate epileptogenesis, increase seizure susceptibility, and impact anticonvulsant drug pharmacokinetics, immune system function, and brain physiology. Viral infections significantly impact the clinical management of epilepsy patients, necessitating a multidisciplinary approach encompassing diagnosis, prevention, and treatment of both conditions. We delved into the dual dynamics of viruses inducing epilepsy and epilepsy patients acquiring viruses, examining the unique features of each case. For virus-induced epilepsy, we specify virus types, elucidate mechanisms of epilepsy induction, emphasize neuroinflammation's impact, and analyze its effects on anticonvulsant drug pharmacokinetics. Conversely, in epilepsy patients acquiring viruses, we detail the acquired virus, its interaction with existing epilepsy, neuroinflammation effects, and changes in anticonvulsant drug pharmacokinetics. Understanding this interplay advances precision therapies for epilepsy during viral infections, providing mechanistic insights, identifying biomarkers and therapeutic targets, and supporting optimized dosing regimens. However, further studies are crucial to validate tools, discover new biomarkers and therapeutic targets, and evaluate targeted therapy safety and efficacy in diverse epilepsy and viral infection scenarios. [ABSTRACT FROM AUTHOR]

We explored the correlation between the presence of isocitrate dehydrogenase-1 (IDH1) mutations and the incidence of postoperative epilepsy in patients with glioblastoma, as well as assessed the efficacy of preemptive administration of antiepileptic medications in mitigating the occurrence of postoperative epilepsy. Methods: Fifty-three patients who received a postoperative pathological diagnosis of glioblastoma, were enrolled in this study. Tumor specimens were subjected to IDH1 gene analysis. The patient cohort was stratified based on their IDH1 mutation status and the administration of prophylactic antiepileptic drugs during the postoperative phase. We subsequently conducted a comparative analysis of postoperative epileptic complications within each patient subgroup. Results: In the cohort of 53 patients under study, the occurrence of epilepsy was observed in 10 out of 21 patients carrying IDH1 mutations, while 5 out of 32 patients with wild-type IDH1 also experienced epilepsy, revealing a statistically significant difference (P < 0.05). Among the 27 patients who received prophylactic antiepileptic drugs, 6 of them developed epilepsy, whereas 9 out of 26 patients who did not receive prophylactic antiepileptic drugs exhibited concurrent epilepsy, with no statistically significant difference (P > 0.05). However, when performing a subgroup analysis, it was found that 3 out of 12 patients with IDH1 mutations who received prophylactic antiepileptic drugs experienced epilepsy, whereas 7 out of 9 patients who did not receive prophylactic antiepileptic drugs developed epilepsy, demonstrating a statistically significant difference (P < 0.05). Furthermore, within the group of 15 patients with wild-type IDH1, 3 patients who received prophylactic antiepileptic drugs developed epilepsy, while 2 cases of epilepsy occurred among the 17 patients who did not receive prophylactic antiepileptic drugs, with no statistically significant difference (P > 0.05). Conclusion: In individuals with IDH1 mutant glioblastoma who have undergone surgical resection, the implementation of preventive antiepileptic therapy demonstrates a potential to diminish the occurrence of postoperative epilepsy. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aimed to assess the effectiveness and safety of novel antiepileptic drugs (AEDs) in treating epilepsy in patients with brain tumors (BTRE). Methods: A search was conducted on PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to February 2023, with English language restriction. Results: In this meta-analysis, 18 clinical trials involving 755 BTRE patients were included to assess the efficacy and safety of novel AEDs in BTRE treatment. At the last follow-up, a =50% reduction in seizure frequency was experienced by 72% of patients (random-effects model, 95% CI = 0.64-0.78) using novel AEDs. At the last follow-up, seizure freedom was experienced by 34% of patients (random-effects model, 95% CI = 0.28-0.41) using novel AEDs. The pooled incidence of AEs was found to be 19% (95% CI: 13%-26%), with a withdrawal rate due to adverse effects of only 3%. Comparable efficacy and incidence of adverse effects were observed between lacosamide and perampanel. Conclusion: This meta-analysis suggests that novel antiepileptic drugs are deemed effective for seizure control in brain tumor patients, particularly when used as adjunctive therapy. Although lacosamide and perampanel received more focus in studies, no significant difference was observed in the efficacy and adverse reactions of these two drugs in seizure control. Further randomized controlled trials are deemed necessary to validate our findings. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) has been widely used as an antiepileptic drug for decades. Although VPA is effective and well-tolerated, long-term VPA treatment is usually associated with hepatotoxicity. However, the underlying mechanisms of VPAcaused hepatotoxicity remain unclear. In this study, a total of 157 pediatric patients with epilepsy were recruited and divided into normal liver function (NLF, 112 subjects) group and abnormal liver function (ABLF, 45 subjects) group. We observed that MTHFR A1298C and MTHFR C677T variants may be linked to VPA-induced liver dysfunction (p = 0.001; p = 0.023, respectively). We also found that the MTHFR A1298C polymorphism was associated with a higher serum Hcy level (p = 0.001) and a lower FA level (p = 0.001). Moreover, the serum Hcy levels was strongly correlated with the GSH and TBARS concentrations (r = -0.6065, P < 0.001; r = 0.6564, P < 0.001, respectively). Furthermore, logistic analysis indicated that MTHFR A1298C/C677T polymorphisms and increased Hcy concentrations may be risk factors for VPA-induced liver dysfunction. These results suggested that individual susceptibility to VPA-induced liver dysfunction may result from MTHFR A1298C/C677T polymorphisms and increased Hcy levels. This study may be helpful for the prevention and guidance of VPA-induced liver dysfunction. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that mTOR signaling plays an important role in synaptic plasticity. However, the function of S6K1, the mechanistic target of rapamycin kinase complex 1 (mTORC1) substrate, in epilepsy remains unknown. Aims: Our present study aimed to explore the mechanism by which S6K1 is involved in chronic epilepsy. Methods: First, immunostaining was used to measure neurite length and complexity in kainic acid (KA)‐treated primary cultured neurons treated with PF‐4708671, a highly selective S6K1 inhibitor. We obtained evidence for the role of S6K1 in protecting and promoting neuronal growth and development in vitro. Next, to explore the function and mechanism of the S6K1 inhibitor in epilepsy, a pilocarpine‐induced chronic epileptic rat model was established. In vivo electrophysiology (including local field potentiation in CA1 and long‐term potentiation), depression/anxiety‐like behavior tests, and Golgi staining were performed to assess seizure behavior, power spectral density, depression/anxiety‐like behavior, and synaptic plasticity. Furthermore, western blotting was applied to explore the potential molecular mechanisms. Results: We found that inhibition of S6K1 expression significantly decreased seizures and depression‐like behavior and restored power at low frequencies (1–80 Hz), especially in the delta, theta, and alpha bands, in chronic epileptic rats. In addition, PF‐4708671 reversed the LTP defect in hippocampal CA3–CA1 and corrected spine loss and dendritic pathology. Conclusion: In conclusion, our data suggest that inhibition of S6K1 attenuates seizures and depression in chronic epileptic rats via the rescue of synaptic structural and functional deficits. Given the wide range of physiological functions of mTOR, inhibition of its effective but relatively simple functional downstream molecules is a promising target for the development of drugs for epilepsy. [ABSTRACT FROM AUTHOR]

Cenobamate (CNB) is a new anti-seizure medication (ASM) recently introduced in clinical practice after approval by the FDA and EMA for the add-on treatment of focal onset seizures in adult patients. Although its mechanism of action has not been fully understood, CNB showed promising clinical efficacy in patients treated with concomitant ASMs. The accessibility of CNB could pave a way for the treatment of refractory or drug-resistant epilepsies, which still affect at least one-third of the patients under pharmacological treatment. In this context, therapeutic drug monitoring (TDM) offers a massive opportunity for better management of epileptic patients, especially those undergoing combined therapy. Here, we describe the first fully validated ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method for the quantification of CNB and concomitant ASMs in human plasma, with samples extracted either manually or by means of a liquid handler. Our method was validated according to the most recent ICH International Guideline M10 for Bioanalytical Method Validation and Study Sample Analysis. The method proved to be selective for CNB and displayed a linear range from 0.8 to 80 mg/L; no matrix effect was found (98.2 ± 4.1%), while intra-day and inter-day accuracy and precision were within the acceptance range. Also, CNB short- and long-term stability in plasma under different conditions was assessed. Leftover human plasma samples were employed as study samples for method validation. Our method proved to be highly sensitive and selective to quantify CNB and concomitant ASMs in human plasma; therefore, this method can be employed for a routinely TDM-based approach to support physicians in the management of an epileptic patient. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a chronic neurological disease characterized by repeated and unprovoked epileptic seizures. Developing disease‐modifying therapies (DMTs) has become important in epilepsy studies. Notably, focusing on iron metabolism and ferroptosis might be a strategy of DMTs for epilepsy. Blocking the acid‐sensing ion channel 1a (ASIC1a) has been reported to protect the brain from ischemic injury by reducing the toxicity of [Ca2+]i. However, whether inhibiting ASIC1a could exert neuroprotective effects and become a novel target for DMTs, such as rescuing the ferroptosis following epilepsy, remains unknown. Methods: In our study, we explored the changes in ferroptosis‐related indices, including glutathione peroxidase (GPx) enzyme activity and levels of glutathione (GSH), iron accumulation, lipid degradation products‐malonaldehyde (MDA) and 4‐hydroxynonenal (4‐HNE) by collecting peripheral blood samples from adult patients with epilepsy. Meanwhile, we observed alterations in ASIC1a protein expression and mitochondrial microstructure in the epileptogenic foci of patients with drug‐resistant epilepsy. Next, we accessed the expression and function changes of ASIC1a and measured the ferroptosis‐related indices in the in vitro 0‐Mg2+ model of epilepsy with primary cultured neurons. Subsequently, we examined whether blocking ASIC1a could play a neuroprotective role by inhibiting ferroptosis in epileptic neurons. Results: Our study first reported significant changes in ferroptosis‐related indices, including reduced GPx enzyme activity, decreased levels of GSH, iron accumulation, elevated MDA and 4‐HNE, and representative mitochondrial crinkling in adult patients with epilepsy, especially in epileptogenic foci. Furthermore, we found that inhibiting ASIC1a could produce an inhibitory effect similar to ferroptosis inhibitor Fer‐1, alleviate oxidative stress response, and decrease [Ca2+]i overload by inhibiting the overexpressed ASIC1a in the in vitro epilepsy model induced by 0‐Mg2+. Conclusion: Inhibiting ASIC1a has potent neuroprotective effects via alleviating [Ca2+]i overload and regulating ferroptosis on the models of epilepsy and may act as a promising intervention in DMTs. [ABSTRACT FROM AUTHOR]

Objective: Absence seizures result from aberrant thalamocortical processing that confers synchronous, bilateral spike-and-wave discharges (SWDs) and behavioral arrest. Previous work has demonstrated that SWDs can result from enhanced thalamic tonic inhibition, consistent with the mechanism of first-line antiabsence drugs that target thalamic low-voltage-activated calcium channels. However, nearly half of patients with absence epilepsy are unresponsive to first-line medications. In this study we evaluated the role of cortical tonic inhibition and its manipulation on absence seizure expression. Methods: We used video-electroencephalogram (EEG) monitoring to show that mice with a γ-aminobutyric acid type A (GABAA) receptor mutation (γ2R43Q) display absence seizures. Voltage-clamp recordings in brain slices from wild type and γ2R43Q mice were used to evaluate the amount of tonic inhibition and its selective pharmacological modulation. Finally, we determined whether modulating tonic inhibition controls seizure expression. Results: γ2R43Q mice completely lack tonic inhibition in principal neurons of both layer 2/3 cortex and ventrobasal thalamus. Blocking cortical tonic inhibition in wild type mice is sufficient to elicit SWDs. Tonic inhibition in slices from γ2R43Q mice could be rescued in a dose-dependent fashion by the synthetic neurosteroid ganaxolone. Low-dose ganaxolone suppressed seizures in γ2R43Q mice. Conclusions: Our data suggest that reduced cortical tonic inhibition promotes absence seizures and that normal function can be restored via selective pharmacological rescue. These results, together with previous findings, suggest that deviations of tonic inhibition either above or below an optimal set point can contribute to absence epilepsy. Returning the thalamocortical system to this set point may provide a novel treatment for refractory absence epilepsy. [ABSTRACT FROM AUTHOR]

Background and purpose: We aimed to evaluate (i) glymphatic system function in patients with focal epilepsy in comparison with healthy controls, and (ii) the association between anti‐seizure medication (ASM) response and glymphatic system function by using diffusion tensor image analysis along the perivascular space (DTI‐ALPS). Methods: We retrospectively enrolled 100 patients with focal epilepsy who had normal brain magnetic resonance imaging (MRI) findings, and classified them as "poor" or "good" ASM responders according to their seizure control at the time of brain MRI. We also included 79 age‐ and sex‐matched healthy controls. All patients and healthy controls underwent conventional brain MRI and diffusion tensor imaging. The DTI‐ALPS index was calculated using the DSI studio program. Results: Of the 100 patients with focal epilepsy, 38 and 62 were poor and good ASM responders, respectively. The DTI‐ALPS index differed significantly between patients with focal epilepsy and healthy controls and was significantly lower in patients with focal epilepsy (1.55 vs. 1.70; p < 0.001). The DTI‐ALPS index also differed significantly according to ASM response and was lower in poor ASM responders (1.48 vs. 1.59; p = 0.047). Furthermore, the DTI‐ALPS index was negatively correlated with age (r = −0.234, p = 0.019) and duration of epilepsy (r = −0.240, p = 0.016) in patients with focal epilepsy. Conclusion: Our study is the first to identify, in focal epilepsy patients, a greater reduction in glymphatic system function among poor ASM responders compared to good responders. To confirm our results, further prospective multicenter studies with large sample sizes are needed. [ABSTRACT FROM AUTHOR]

Direct cortical stimulation has been applied in epilepsy for nearly a century and has experienced a renaissance, given unprecedented opportunities to probe, excite, and inhibit the human brain. Evidence suggests stimulation can increase diagnostic and therapeutic utility in patients with drug‐resistant epilepsies. However, choosing appropriate stimulation parameters is not a trivial issue, and is further complicated by epilepsy being characterized by complex brain state dynamics. In this article derived from discussions at the ICTALS 2022 Conference (International Conference on Technology and Analysis for Seizures), we succinctly review the literature on cortical stimulation applied acutely and chronically to the epileptic brain for localization, monitoring, and therapeutic purposes. In particular, we discuss how stimulation is used to probe brain excitability, discuss evidence on the usefulness of stimulation to trigger and stop seizures, review therapeutic applications of stimulation, and finally discuss how stimulation parameters are impacted by brain dynamics. Although research has advanced considerably over the past decade, there are still significant hurdles to optimizing use of this technique. For example, it remains unclear to what extent short timescale diagnostic biomarkers can predict long‐term outcomes and to what extent these biomarkers add information to already existing biomarkers from passive electroencephalographic recordings. Further questions include the extent to which closed loop stimulation offers advantages over open loop stimulation, what the optimal closed loop timescales may be, and whether biomarker‐informed stimulation can lead to seizure freedom. The ultimate goal of bioelectronic medicine remains not just to stop seizures but rather to cure epilepsy and its comorbidities. [ABSTRACT FROM AUTHOR]

Sexual dysfunction is common after using antiepileptic drugs, and anorgasmia can occur as a treatment-emergent adverse event. The positive effect of lamotrigine on improving anorgasmia in epilepsy patients has been reported in a few studies. Anorgasmia is a common manifestation in epileptic patients. Anorgasmia or ejaculation without achieving orgasm is permanent or recurrent, happening despite adequate stimulation. The current paper presented a 31-year-old male with epilepsy since early childhood who received carbamazepine and phenobarbital. He experienced anorgasmia, and by switching to valproate sodium, the seizures and anorgasmia were somewhat improved. However, both problems were completely resolved after receiving lamotrigine. An 18-month follow-up did not reveal any particular issue. Lamotrigine can be recommended alongside other antiepileptic drugs in patients who have cure-induced anorgasmia. Considering the improvement of anorgasmia and reduced number of seizures, long-term follow-up is recommended. [ABSTRACT FROM AUTHOR]

Background: Approximately one quarter of people with an intellectual disability (PwID) have epilepsy of whom nearly three-quarters are pharmaco-resistant. There are higher reported neuropsychiatric side-effects to anti-seizure medication (ASM) in this group. Levetiracetam (LEV) is a first-line ASM with a stronger association with neuropsychiatric symptoms for PwID than other ASMs. Brivaracetam (BRV) is a newer ASM. Recent studies suggest a beneficial effect of swapping people who experience neuropsychiatric events with LEV to BRV. However, there is limited evidence of this for PwID. This evaluation analyses real world outcomes of LEV to BRV swap for PwID compared to those without ID. Methods: We performed a multicentre, retrospective review of clinical records. Demographic, clinical characteristics and reported adverse events of patients switched from LEV to BRV (2016–2020) were recorded at 3 months pre and 6- and 12-month post-BRV initiation. Outcomes were compared between PwID and those without and summarised using cross-tabulations and logistic regression models. A Bonferroni correction was applied. Results: Of 77 participants, 46 had ID and 52% had a past psychiatric illness. 71% participants switched overnight from LEV to BRV. Seizure reduction of > 50% was seen in 40% patients. Psychiatric illness history was predictive of having neuropsychiatric side-effects with LEV but not BRV (p = 0.001). There was no significant difference for any primary outcomes between PwID versus without ID. Conclusions: Switching from LEV to BRV appears as well tolerated and efficacious in PwID as those without ID with over 90% still on BRV after 12 months. [ABSTRACT FROM AUTHOR]

Objective: Perampanel is an oral anti‐seizure medication, which is approved in Japan for focal‐onset seizures, with/without focal to bilateral tonic–clonic seizures, as monotherapy/adjunctive therapy in patients aged 4 years and older. Treatment for generalized tonic–clonic seizures as adjunctive therapy in patients aged 12 years and older is approved as well. We evaluated the feasibility of intravenous (IV) administration of perampanel as an alternative to oral administration. Methods: Study 240 (NCT03754582) was an uncontrolled, open‐label study of IV perampanel, conducted in 21 Japanese patients with epilepsy who received a stable dose of 8–12 mg/day of oral perampanel. Patients received 30‐minute IV infusions at equivalent daily doses of oral perampanel for 4 days, then were switched back to oral perampanel. Safety, tolerability, plasma concentration, and maintenance of efficacy throughout the transition between IV and oral dosing of perampanel were assessed. As supportive data, a subgroup analysis was also conducted using data from healthy Japanese subjects (n = 18) who were enrolled in Study 050 (NCT03376997) investigating the pharmacokinetics and safety of IV perampanel in healthy subjects who received an IV infusion (30‐, 60‐, or 90‐minute) of perampanel 12 mg and a single oral administration of perampanel 12‐mg tablet. Results: In Study 240, the transition between 30‐minute IV and oral perampanel dosing was associated with a ≤1.4‐fold increase in the mean change in maximum observed concentration of perampanel. Seizure outcomes demonstrated no considerable changes in efficacy before, during, or after 30‐minute IV dosing of perampanel. The safety profiles were similar between IV and oral formulations. In Study 050, the pharmacokinetics of 30‐ or 60‐minute IV infusion of perampanel further support the interchangeability between oral and IV formulations in the Japanese subjects. Significance: These results support that 30‐minute IV perampanel may be a potential short‐term alternative to oral formulations for patients with epilepsy. [ABSTRACT FROM AUTHOR]

A Real-World Comparison Among Third-Generation Antiseizure Medications: Results From the COMPARE Study Roberti R, Di Gennaro G, Anzellotti F, Arnaldi D, Belcastro V, Beretta S, Boero G, Bonanni P, Canafoglia L, D'Aniello A, Dainese F, De Caro C, Di Gennaro G, Di Giacomo R, DiFrancesco JC, Dono F, Falcicchio G, Ferlazzo E, Foschi N, Franciotta S, Gambardella A, Giordano A, Iannone LF, Labate A, La Neve A, Lattanzi S, Leggio U, Liguori C, Maschio M, Nilo A, Operto FF, Pascarella A, Pauletto G, Renna R, Strigaro G; COMPARE Study Group; Russo E. Epilepsia. 2023. doi:10.1111/epi.17843. PMID: 38052481 Objective: There are few comparative data on the third-generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives. Methods: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add-on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan-Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by 2 multilevel logistic models. Results: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)-naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.29) and PER groups (HR = 1.64, 95% CI = 1.06-2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71-16.61), as well as PER-treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05-2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] =.08, 95% CI =.01-.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV-naïve (OR = 10.32, 95% CI = 1.55-68.78) versus men. PER (OR = 6.93, 95% CI = 3.32-14.44) and BRV in LEV-naïve patients (OR = 6.80, 95% CI = 2.64-17.52) had a higher chance of AEs than LCM. Significance: Comparative evidence from real-world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics. [ABSTRACT FROM AUTHOR]

Background: Despite the plethora of pharmacotherapy and acquisition of new AEDs, there is a hard core of patients who persistently fail to respond to optimal treatment and continue to suffer from refractory seizures. We aimed to study the prevalence and risk factors for development of drug-resistant epilepsy (DRE). All adult patients with epilepsy (PWE) who attended the epilepsy outpatient clinic and were maintained on at least two anti-epileptic drugs (AEDs) were profiled for drug response in accordance with the International League against Epilepsy (ILAE) 2010 consensus definition for DRE. Data collected included demographics, detailed history of seizures, medications history, past medical and psychiatric history, electroencephalogram, and brain imaging findings. Results: The prevalence rate of DRE was 21.3% in the study population. Significant variables on univariate analysis were the following: male gender (OR: 5.409, CI 1.661–17.617, p < 0.005), presence of GTC (OR: 4.187, CI 1.304–13.445, p < 0.016), no change in frequency after AEDs use (OR: 4.465, CI 1.211–16.468, p < 0.025), bad response to first AEDs (OR: 9.000, CI 2.437–33.244, p < 0.001), presence of developmental delay (OR: 10.612, CI 1.347–83.589, p < 0.025), presence of abnormal neurological examination (OR: 4.227, CI 1.145–15.601, p < 0.030), generalized epilepsy (OR: 3.886, CI 1.141–13.233, p < 0.030), presence of structural etiology (OR: 3.467, CI 1.152–10.431, p < 0.027), abnormal EEG findings (OR: 3.467, CI 1.152–10.431, p < 0.027), presence of focal activity in EEG (OR: 5.344, CI 1.155–24.713, p < 0.032), and abnormal imaging findings (OR: 3.524, CI 1.083–11.473, p < 0.036). In the logistic regression analysis, two variables were statistically significant: bad response to the first AED and no change in seizure frequencies with treatment. Our study showed that older age at seizure onset was a protective factor for DRE. Conclusions: The current study suggests that significant risk factors for DRE are younger age at epilepsy onset, poor response to first AED and lack of change in seizure frequencies after adjusting treatment. [ABSTRACT FROM AUTHOR]

Despite progress in the development of anti‐seizure medications (ASMs), one third of people with epilepsy have drug‐resistant epilepsy (DRE). The working definition of DRE, proposed by the International League Against Epilepsy (ILAE) in 2010, helped identify individuals who might benefit from presurgical evaluation early on. As the incidence of DRE remains high, the TASK1 workgroup on DRE of the ILAE/American Epilepsy Society (AES) Joint Translational Task Force discussed the heterogeneity and complexity of its presentation and mechanisms, the confounders in drawing mechanistic insights when testing treatment responses, and barriers in modeling DRE across the lifespan and translating across species. We propose that it is necessary to revisit the current definition of DRE, in order to transform the preclinical and clinical research of mechanisms and biomarkers, to identify novel, effective, precise, pharmacologic treatments, allowing for earlier recognition of drug resistance and individualized therapies. [ABSTRACT FROM AUTHOR]

Introduction: Annexin A2 (ANXA2) participates in the pathology of a variety of diseases. Nevertheless, the impact of ANXA2 on epilepsy remains to be clarified. Aims: Hence, the study aimed at investigating the underlying role of ANXA2 in epilepsy through behavioral, electrophysiological, and pathological analyses. Results: It was found that ANXA2 was markedly upregulated in the cortical tissues of temporal lobe epilepsy patients (TLE), kainic acid (KA)‐induced epilepsy mice, and in a seizure‐like model in vitro. ANXA2 silencing in mice suppressed first seizure latency, number of seizures, and seizure duration in behavioral analysis. In addition, abnormal brain discharges were less frequent and shorter in the hippocampal local field potential (LFP) record. Furthermore, the results showed that the frequency of miniature excitatory postsynaptic currents was decreased in ANXA2 knockdown mice, indicating that the excitatory synaptic transmission is reduced. Co‐immunoprecipitation (COIP) experiments demonstrated that ANXA2 interacted with the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) subunit GluA1. Moreover, ANXA2 knockdown decreased GluA1 expression on the cell surface and its phosphorylation onserine 831 and serine 845, related to the decreased phosphorylation levels mediated by protein kinases A and C (PKA and PKC). Conclusions: This study covers a previously unknown and key function of ANXA2 in epilepsy. These findings indicate that ANXA2 can regulate excitatory synaptic activity mediated by AMPAR subunit GluA1 to improve seizure activity, which can provide novel insights for the treatment and prevention of epilepsy. [ABSTRACT FROM AUTHOR]

(1) Background: This study presents the baseline characteristics of a community-level population of people with epilepsy (n = 1975) living in an area endemic for Taenia solium, the pathogen responsible for neurocysticercosis (NCC). (2) Methods: Participants were sequentially enrolled in a clinical cohort from 2007 to 2020 in Tumbes, Peru. All participants provided demographic and clinical history and received clinical evaluations. Diagnostics, including neuroimaging, cysticercosis serologies, and EEG, were obtained where possible. The data presented are from the cross-sectional baseline assessment of cohort participants. (3) Results: Approximately 38% of participants met the criteria for NCC. Those with NCC were more likely to have adult-onset epilepsy, as well as a longer duration of epilepsy, as compared to their counterparts without NCC. Overall, the data indicate a large treatment gap, with only approximately a quarter of the baseline population with prescriptions for anti-seizure medications. (4) Conclusions: These data reveal a high proportion of NCC among people living with epilepsy in these communities, with limited health care resources. At baseline, 74% of the population were not receiving anti-seizure treatments. Further analyses of these data will clarify the natural history of the disease for this population. [ABSTRACT FROM AUTHOR]

Voltage-gated sodium (Nav) channels govern membrane excitability, thus setting the foundation for various physiological and neuronal processes. Nav channels serve as the primary targets for several classes of widely used and investigational drugs, including local anesthetics, antiepileptic drugs, antiarrhythmics, and analgesics. In this study, we present cryogenic electron microscopy (cryo-EM) structures of human Nav1.7 bound to two clinical drugs, riluzole (RLZ) and lamotrigine (LTG), at resolutions of 2.9 Å and 2.7 Å, respectively. A 3D EM reconstruction of ligand-free Nav1.7 was also obtained at 2.1 Å resolution. RLZ resides in the central cavity of the pore domain and is coordinated by residues from repeats III and IV. Whereas one LTG molecule also binds to the central cavity, the other is found beneath the intracellular gate, known as site BIG. Therefore, LTG, similar to lacosamide and cannabidiol, blocks Nav channels via a dual-pocket mechanism. These structures, complemented with docking and mutational analyses, also explain the structure–activity relationships of the LTG-related linear 6,6 series that have been developed for improved efficacy and subtype specificity on different Nav channels. Our findings reveal the molecular basis for these drugs’ mechanism of action and will aid the development of novel antiepileptic and pain-relieving drugs. [ABSTRACT FROM AUTHOR]

Background: Overall, up to one-third of epilepsy patients have drug-resistant epilepsy. However, there was previously no meta-analysis to support the guidelines for broad-spectrum antiseizure medication selection for the adjunctive treatment of refractory epilepsy. In the present meta-analysis, we assessed the efficacy and safety of three second-generation broad-spectrum antiseizure medications, lamotrigine (LTG), levetiracetam (LEV), and topiramate (TPM), and two third-generation broad-spectrum antiseizure medications, perampanel (PER) and lacosamide (LCM), for the adjunctive treatment of refractory epilepsy. Methods: We systematically searched PubMed, Embase, and CENTRAL from inception to July 15, 2022. The studies included in the meta-analysis were required to meet the following criteria: (1) be randomized, double-blind clinical trials; (2) include patients aged >2 years with a clinical diagnosis of drug-resistant epilepsy; (3) have at least 8 weeks for the treatment period excluding the titration phase; and (4) report the outcomes of seizure response, seizure freedom and the withdrawal rate due to treatment-emergent adverse effects. Data were extracted, and the risk of bias for each study was assessed by two authors independently using RoB2 tools. We performed the network meta-analysis for each outcome through a group of programs in the mvmeta and network packages in Stata. Relative odds ratios with 95% confidence intervals were calculated as the result of the analyses. The surface under the cumulative ranking curve (SUCRA) and mean ranks were used to rank these treatments. Results: Forty-two randomized controlled trials (RCTs) (LTG-placebo: n = 6, LEV-placebo: n = 13, TPM-placebo: n = 9, PER-placebo: n = 6, LCM-placebo: n = 7, LEV-TPM: n = 1) with 10257 participants (LTG = 569, LEV = 1626, TPM = 701, PER = 1734, LCM = 1908, placebo = 3719) were included. Levetiracetam had subequal efficacy in 50 % seizure frequency reduction to TPM [odds ratio (OR) 1.00, 95% confidence interval (CI) 0.73–1.38], and LEV had a higher rate of ≥ 50% seizure frequency reduction than LCM (OR 1.49, 95% CI 1.11–2.01) and PER (OR 1.68, 95% CI 1.24–2.29). Levetiracetam was also related to a higher proportion of seizure freedom participants than TPM (OR 1.87, 95% CI 1.20–2.89), PER (OR 2.23, 95% CI 1.12–4.43), and LCM (OR 2.97, 95% CI 1.46–6.05). In addition, LEV was associated with a lower risk of experiencing at least one treatment-emergent adverse event (TEAE) than PER (OR 0.63, 95% CI 0.46–0.85) and TPM (OR 0.51, 95 % CI 0.36–0.72) and a lower proportion of patients experiencing TEAEs leading to discontinuation than PER (OR 0.51, 95% CI 0.27–0.97) and TPM (OR 0.50, 95 % CI 0.27–0.93). Conclusions: Third-generation drugs (PER and LCM) had no advantages in terms of efficacy and safety for adjunctive treatment of refractory epilepsy compared with several second-generation drugs (LEV and LTG). Levetiracetam was the priority choice for adjunctive treatment of refractory epilepsy. Perampanel and LCM had no advantages in terms of efficacy and safety among the five drugs. Registration: PROSPERO registration number, CRD42022344153; last edited on December 23, 2022. [ABSTRACT FROM AUTHOR]

Background: Pathogenic variants in the GAP activity towards RAGs 1 (GATOR1) complex genes (DEPDC5, NPRL2, NPRL3) cause focal epilepsy through hyperactivation of the mechanistic target of rapamycin pathway. We report our experience using everolimus in patients with refractory GATOR1‐related epilepsy. Methods: We performed an open‐label observational study of everolimus for drug‐resistant epilepsy caused by variants in DEPDC5, NPRL2 and NPRL3. Everolimus was titrated to a target serum concentration (5–15 ng/mL). The primary outcome measure was change in mean monthly seizure frequency compared with baseline. Results: Five patients were treated with everolimus. All had highly active (median baseline seizure frequency, 18/month) and refractory focal epilepsy (failed 5–16 prior anti‐seizure medications). Four had DEPDC5 variants (three loss‐of‐function, one missense) and one had a NPRL3 splice‐site variant. All patients with DEPDC5 loss‐of‐function variants had significantly reduced seizures (74.3%–86.1%), although one stopped everolimus after 12 months due to psychiatric symptoms. Everolimus was less effective in the patient with a DEPDC5 missense variant (43.9% seizure frequency reduction). The patient with NPRL3‐related epilepsy had seizure worsening. The most common adverse event was stomatitis. Conclusions: Our study provides the first human data on the potential benefit of everolimus precision therapy for epilepsy caused by DEPDC5 loss‐of‐function variants. Further studies are needed to support our findings. [ABSTRACT FROM AUTHOR]

Simple Summary: We introduce the term and evaluate the phenomenon of pseudoresistance to antiseizure-medication in canine epilepsy cases initially diagnosed with medication-resistant epilepsy. Our study shows that around one third of the patients initially diagnosed with medication-resistant epilepsy had in fact other underlying reasons for their drug resistance (they were in fact pseudoresistant) and all but one of these cases responded to modification of the initial therapy protocol. Epilepsy is a common neurological disorder in veterinary practice, complicated by frequent occurrence of medication-resistant epilepsy. In human medicine, it has been noted that some patients with medication-resistant epilepsy have in fact other reasons for their apparent medication-resistance. The aim of this retrospective study was to describe the issue of pseudoresistance using as an example a population of dogs presented with presumed medication-resistant epilepsy and provide an in-depth review of what is known in human medicine about pseudoresistant epilepsy. One-hundred fifty-two cases were identified with medication-resistant epilepsy, of which 73% had true medication-resistant epilepsy and 27% patients had pseudoresistance. Low serum anti-seizure medication levels were the most common cause of pseudoresistance, present in almost half of the cases (42%), followed by inadequate choice of drugs or dosages (22%), misclassification (22%) or misdiagnosis (9%) of epilepsy and poor compliance (9%). All cases of pseudoresistance, except for one, responded to a modification of the initial therapy protocol. Pseudoresistance can bias clinical trials, misinform the clinical decision-making process, delay diagnosis and treatment, and misinform owners about their pets' prognosis. A substantial proportion of these cases can have improvement of their seizure frequency or achieve seizure freedom upon modification of their therapeutic protocol. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy is a chronic disorder, and approximately 25% to 30% of dogs with epilepsy are refractory to anti‐epileptic drugs. As increased activity has been shown to reduce seizure frequency in people with epilepsy, the goal of this study was to evaluate the relationship between deviation from baseline activity and seizure incidence in dogs with epilepsy. Materials and Methods: Activity and seizure data were obtained using a canine activity monitoring device and owner observed seizure logs in 53 dogs with idiopathic epilepsy receiving anti‐epileptic drugs. Each dog's activity was individually measured, and 14‐day baseline averages were calculated. Logistic regression was performed to evaluate how an observed increase in activity, ranging from 0% to 50%, above baseline activity, affects the incidence of a seizure in the following 24 hours. Results: A total of 8540 activity days and 365 seizure days were used in the final analysis with an average of 11 seizures per dog (range 0 to 30 seizures). Seizure incidence was significantly more likely when activity was 10%, 20%, or 30% above baseline activity in the 24 hours before the day of a documented seizure [95% confidence interval (1.02 to 1.60), P=0.033; 95% confidence interval (1.08 to 1.80), P=0.010; 95% confidence interval (1.13 to 2.07), P=0.005, respectively]. However, when activity levels were 40% and 50% above baseline, the effect diminished (95% confidence interval (0.74 to 1.70), P=0.532; or 95% confidence interval (0.56 to 1.66), P=0.988, respectively). Clinical Significance: Differently than in humans, this study demonstrated that a mild to moderate increase in activity resulted in a higher seizure incidence within 24 hours in dogs with epilepsy. [ABSTRACT FROM AUTHOR]

An imbalance between excitation (E) and inhibition (I) in the brain has been identified as a key pathophysiology of epilepsy over the years. The hippocampus and amygdala in the limbic system play a crucial role in the initiation and conduction of epileptic seizures and are often referred to as the transfer station and amplifier of seizure activities. Existing animal and imaging studies reveal that the hippocampus and amygdala, which are significant parts of the vagal afferent network, can be modulated in order to generate an antiepileptic effect. Using stereo-electroencephalography (SEEG) data, we examined the E/I imbalance in the hippocampus and amygdala of ten drug-resistant epilepsy children treated with acute vagus nerve stimulation (VNS) by estimating the 1/f power slope of hippocampal and amygdala signals in the range of 1–80 Hz. While the change in the 1/f power slope from VNS-BASE varied between different stimulation amplitudes and brain regions, it was more prominent in the hippocampal region. In the hippocampal region, we found a flatter 1/f power slope during VNS-ON in patients with good responsiveness to VNS under the optimal stimulation amplitude, indicating that the E/I imbalance in the region was improved. There was no obvious change in 1/f power slope for VNS poor responders. For VNS non-responders, the 1/f power slope slightly increased when the stimulation was applied. Overall, this study implies that the regulation of E/I imbalance in the epileptic brain, especially in the hippocampal region, may be an acute intracranial effect of VNS. [ABSTRACT FROM AUTHOR]

Objectives: Patients with self-limited epilepsy with centrotemporal spikes (SeLECTS) with electrical status epilepticus in sleep (ESES) have generalized cognitive impairment, yet treatment options are limited. Our study aimed to examine the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on SeLECTS with ESES. In addition, we applied electroencephalography (EEG) aperiodic components (oset and slope) to investigate the improvement of rTMS on the excitation-inhibition imbalance (E-I imbalance) in the brain of this group of children. Methods: Eight SeLECTS patients with ESES were included in this study. Low-frequency rTMS (≤1Hz) was applied for 10 weekdays in each patient. To assess the clinical efficacy and changes in E-I imbalance, EEG recordings were performed both before and after rTMS. Seizure-reduction rate and spike-wave index (SWI) weremeasured to investigate the clinical effects of rTMS. The aperiodic offset and slope were calculated to explore the effect of rTMS on E-I imbalance. Results: Five of the eight patients (62.5%) were seizure-free within 3 months after stimulation, with treatment effects decreasing with longer follow-ups. The SWI decreased significantly at 3 and 6 months after rTMS compared with the baseline (P = 0.0157 and P = 0.0060, respectively). The offset and slope were compared before rTMS and within 3months after stimulation. The results showed a significant reduction in the offset after stimulation (P < 0.0001). There was a remarkable increase in slope after the stimulation (P < 0.0001). Conclusion: Patients achieved favorable outcomes in the first 3 months after rTMS. The ameliorative effect of rTMS on SWI may last up to 6 months. Low-frequency rTMS could reduce firing rates in neuronal populations throughout the brain, which was most pronounced at the site of stimulation. A significant reduction in the slope after rTMS treatment suggested an improvement in the E-I imbalance in the SeLECTS. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) with electroencephalography (EEG), that is TMS‐EEG, may assist in managing epilepsy. We systematically reviewed the quality of reporting and findings in TMS‐EEG studies on people with epilepsy and healthy controls, and on healthy individuals taking anti‐seizure medication. We searched the Cochrane Library, Embase, PubMed and Web of Science databases for original TMS‐EEG studies comparing people with epilepsy and healthy controls, and healthy subjects before and after taking anti‐seizure medication. Studies should involve quantitative analyses of TMS‐evoked EEG responses. We evaluated the reporting of study population characteristics and TMS‐EEG protocols (TMS sessions and equipment, TMS trials and EEG protocol), assessed the variation between protocols, and recorded the main TMS‐EEG findings. We identified 20 articles reporting 14 unique study populations and TMS methodologies. The median reporting rate for the group of people with epilepsy parameters was 3.5/7 studies and for the TMS parameters was 13/14 studies. TMS protocols varied between studies. Fifteen out of 28 anti‐seizure medication trials in total were evaluated with time‐domain analyses of single‐pulse TMS‐EEG data. Anti‐seizure medication significantly increased N45, and decreased N100 and P180 component amplitudes but in marginal numbers (N45: 8/15, N100: 7/15, P180: 6/15). Eight articles compared people with epilepsy and controls using different analyses, thus limiting comparability. The reporting quality and methodological uniformity between studies evaluating TMS‐EEG as an epilepsy biomarker is poor. The inconsistent findings question the validity of TMS‐EEG as an epilepsy biomarker. To demonstrate TMS‐EEG clinical applicability, methodology and reporting standards are required. [ABSTRACT FROM AUTHOR]

We evaluate adherence to tailor made, short-term home exercise programme in adult people with epilepsy (PWE), with seizures controlled on anti-seizure medications (ASM). Demographic, clinical, quality of life (QoL) and physical fitness data of 116 PWE. Participants were prescribed tailor-made home-based exercises for 3 months. At follow-up, adherence to exercise was evaluated using self-reported Exercise Adherence Rating Scale (EARS). Average age of the study population was 29.93 ± 10.20(18–52) years; with 46 (39.6%) women. At enrolment, none of the participants reported to be physically active and the average body mass index (BMI) was 28.40 ± 5.79(18.2–41.4). The average distance walked in a six-minute walk test was 385.95 ± 63.48(240–510) metres. On QoL analysis, the mean Physical component score was 45.57 ± 8.72(25.7–62.6) and Mental component core was 45.41 ± 10.37(20.9–64.9). On EARS, 31(26.7%) participants reported doing exercises as recommended. Among PWE who were non-adherent to exercise, 68(58.6%) reported fear of possible seizure as a barrier for exercise, 63(54.3%) reported lack of support from family and friends. Having no fear about exercise (r = 0.640; p < 0.001) and encouragement of family were associated with adherence to exercise (r = 0.463; p < 0.001). Adherence to home-based physical exercise is reported in one-fourth of PWE. Non-compliance to exercise in PWE is multi-factorial, support from family and friends and counselling may be helpful. CTRI/2014/10/005125 [ABSTRACT FROM AUTHOR]

Withdrawal of anti‐seizure medication (ASM) is challenging, especially in patients with recurrent seizures. Only limited evidence exists regarding the success rate and recurrence risk factors after withdrawal of ASM for a second time in patients with pediatric‐onset epilepsy. In this observational study, we evaluated 104 patients with recurrent pediatric‐onset epilepsy who had ASM withdrawn for a second time. The success rate was 41.3% after the second withdrawal of ASM. The absence of a self‐limiting epilepsy syndrome, shorter seizure‐free intervals before the second withdrawal of ASM, and relapse during tapering after the initial withdrawal of ASM were negative factors significantly associated with the success of ASM withdrawal for a second time. Even after a second seizure recurrence, all patients eventually became seizure‐free after restarting their previous ASM (78.7%) or readjusting the ASM (21.3%). Our findings that 40% of patients with recurrent pediatric‐onset epilepsy could achieve long‐term seizure freedom and that all patients with a second seizure recurrence remained seizure‐free suggest that ASM may be withdrawn for a second time after carefully stratifying clinical risk. [ABSTRACT FROM AUTHOR]