Focal Onset Epilepsy Research Articles

The part and the whole: how single nodes contribute to large-scale phase-locking in functional EEG networks

ObjectiveThe application of signal analysis techniques to electroencephalographic (EEG) recordings from epilepsy patients shows that epilepsy involves not only altered neuronal synchronization but also the reorganization of functional EEG networks. This study aims to assess the large-scale phase-locking of such functional networks and how individual network nodes contribute to this collective dynamics. MethodsWe analyze the EEG recorded before, during and after seizures from sixteen patients with pharmacoresistant focal-onset epilepsy. The data is filtered to low (4–30 Hz) and high (80–150 Hz) frequencies. We define the multivariate phase-locking measure and the univariate phase-locking contribution measure. Surrogate signals are used to estimate baseline results expected under the null hypothesis that the EEG is a correlated linear stochastic process. ResultsOn average, nodes from inside and outside the seizure onset zone (SOZ) increase and decrease, respectively, the large-scale phase-locking. This difference becomes most evident in a joint analysis of low and high frequencies. ConclusionsNodes inside and outside the SOZ play opposite roles for the large-scale phase-locking in functional EEG network in epilepsy patients. SignificanceThe application of the phase-locking contribution measure to EEG recordings from epilepsy patients can potentially help in localizing the SOZ.

Epilepsy in inmate patients seen in a high complexity reference hospital in Colombia: A cross-sectional study.

To describe the sociodemographic and clinical characteristics of imprisoned patients with epilepsy seen at Samaritana University Hospital (HUS) in Bogotá D.C., between January 2017 and November 2020. Cross-sectional cohort study of inmate patients over 18 years of age seen at HUS between January 2017 and November 2020, with a discharge diagnosis of epilepsy. A descriptive univariate analysis of patient sociodemographic and clinical characteristics was carried out. Overall, 92 patients were included, 95.7% were males with a median age of 32 years (IQR: 26-44); 65% were assessed in the outpatient clinic; median hospital length of stay was 2 days (IQR: 0) and 7.6% required admission to the intensive care unit; 75% had focal onset epilepsy, 63.04% with undetermined etiology 31.52% with structural causes. Polytherapy was found in 53.3%, valproic acid being the most frequently used antiseizure medication in 59.78%; lack of adherence was reported in 15.22% and inadequate seizure control in 81.52%; status epilepticus occurred in 5.34%. A total of 31 EEG recordings and 53 brain images were performed, of which, 29% and 39.62%, respectively, were abnormal. Non-epileptic paroxysmal events were diagnosed in 5.34%, while organic or psychiatric comorbidities were found in 25%, and the use of psychoactive substances was documented in 17.39%. Upon discharge, 93.47% had no disability, and only 45.65% returned for outpatient follow-up. The clinical profile was of men in the fourth decade of life with focal onset epilepsy characterized by high seizure frequency, most of whom were receiving antiseizure medication, with a high proportion of polytherapy. The results are a point of departure for prospective studies designed to identify points to intervene and improve healthcare for inmates with epilepsy. Inmates are a vulnerable proportion of persons with epilepsy. In this group there are significant differences compared to the general population, especially with greater psychiatric comorbidity and worse control of epileptic seizures due to difficulties in accessing medical care, antiseizure medication and diagnostic tests. We found that the most characteristic population is made up of men in the fourth decade of life with a high frequency of seizures, most of whom were receiving multiple antiseizure medication This study is the first of its kind in Latin America and it is an initial approach to epilepsy in inmates.

Clinical features and genotype-phenotype correlations in epilepsy patients with de novo DYNC1H1 variants.

DYNC1H1 variants are involved on a disease spectrum from neuromuscular disorders to neurodevelopmental disorders. DYNC1H1-related epilepsy has been reported in small cohorts. We dissect the electroclinical features of 34 patients harboring de novo DYNC1H1 pathogenic variants, identify subphenotypes on the DYNC1H1-related epilepsy spectrum, and compare the genotype-phenotype correlations observed in our cohort with the literature. Patients harboring de novo DYNC1H1 pathogenic variants were recruited through international collaborations. Clinical data were retrospectively collected. Latent class analysis was performed to identify subphenotypes. Multivariable binary logistic regression analysis was applied to investigate the association with DYNC1H1 protein domains. DYNC1H1-related epilepsy presented with infantile epileptic spasms syndrome (IESS) in 17 subjects (50%), and in 25% of these individuals the epileptic phenotype evolved into Lennox-Gastaut syndrome (LGS). In 12 patients (35%), focal onset epilepsy was defined. In two patients, the epileptic phenotype consisted of generalized myoclonic epilepsy, with a progressive phenotype in one individual harboring a frameshift variant. In approximately 60% of our cohort, seizures were drug-resistant. Malformations of cortical development were noticed in 79% of our patients, mostly on the lissencephaly-pachygyria spectrum, particularly with posterior predominance in a half of them. Midline and infratentorial abnormalities were additionally reported in 45% and 27% of subjects. We have identified three main classes of subphenotypes on the DYNC1H1-related epilepsy spectrum. We propose a classification in which pathogenic de novo DYNC1H1 variants feature drug-resistant IESS in half of cases with potential evolution to LGS (Class 1), developmental and epileptic encephalopathy other than IESS and LGS (Class 2), or less severe focal or genetic generalized epilepsy including a progressive phenotype (Class 3). We observed an association between stalk domain variants and Class 1 phenotypes. The variants p.Arg309His and p.Arg1962His were common and associated with Class 1 subphenotype in our cohort. These findings may aid genetic counseling of patients with DYNC1H1-related epilepsy.

Effectiveness and Safety of Adjunctive Cenobamate in People with Focal-Onset Epilepsy: Evidence from the First Interim Analysis of the BLESS Study.

Despite new anti-seizure medications (ASMs) being introduced into clinical practice, about one-third of people with epilepsy do not reach seizure control. Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. In randomized controlled trials, adjunctive cenobamate reduced the frequency of focal seizures in people with uncontrolled epilepsy. Studies performed in real-world settings are useful to complement this evidence and better characterize the drug profile. The Italian BLESS ("Cenobamate in Adults With Focal-Onset Seizures") study is an observational cohort study aimed to evaluate the effectiveness, tolerability, and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy in the context of real-world clinical practice. The study is ongoing and conducted at 50 centers in Italy. This first interim analysis includes participants enrolled until June 2023 and with 12-week outcome data available. Forty participants with a median age of 36.5 (interquartile range [IQR] 26.0-47.5) years were included. The median monthly seizure frequency at baseline was 6.0 (IQR 2.5-17.3) seizures and 31 (77.5%) participants had failed four or more ASMs before cenobamate. At 12 weeks from starting cenobamate, the median reduction in monthly seizure frequency was 52.8% (IQR 27.1-80.3%); 22 (55.0%) participants had a ≥ 50% reduction in baseline seizure frequency and six (15.0%) reached seizure freedom. The median number of concomitant ASMs decreased from 3 (IQR 2-3) at baseline to 2 (IQR 2-3) at 12 weeks and the proportion of patients treated with > 2 concomitant ASMs decreased from 52.5% to 40.0%. Seven (17.5%) patients reported a total of 12 adverse events, 11 of which were considered adverse drug reactions to cenobamate. In adults with uncontrolled focal seizures, the treatment with adjunctive cenobamate was well tolerated and was associated with improved seizure control and a reduction of the burden of concomitant ASMs. NCT05859854 (ClinicalTrials.gov Identifier).

Treatment Outcomes and Healthcare Resource Utilization Among People Living with Focal Onset Epilepsy and Deemed to be Drug Resistant in Clinical Practices in the United States (P10-1.007)

Treatment Outcomes and Healthcare Resource Utilization Among People Living with Focal Onset Epilepsy and Deemed to be Drug Resistant in Clinical Practices in the United States (P10-1.007)

Efficacy and Safety of adjunctive Perampanel in a prospective, real-world, Phase IV study in Indian patients aged ≥12 years for Treatment of focal-onset Epilepsy: Study 508.

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. 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. 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%. 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. 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.

Latencies to the first interictal epileptiform discharges recorded by the electroencephalography in different epileptic patients

PurposeInterictal epileptiform discharges (IEDs) captured in electroencephalography (EEG) have a high diagnostic value for epileptic patients. Extending the recording time may increase the possibility of obtaining IEDs. The purpose of our research was to determine how long it took for various epileptic individuals to receive their first IEDs.MethodsWe retrospectively analyzed patients who were diagnosed with epilepsy and had no anti-seizure medications (ASMs) between September 2018 and March 2019 in the neurology department of the First Affiliated Hospital of Xi'an Jiaotong University. Each individual underwent a 24-h long-term video electroencephalographic monitoring (VEM) procedure. Clinical information including age, gender, age of seizure onset, frequency of seizures, the interval between last seizure and VEM, and results of neuroimaging were gathered. We also calculated the times from the start of the VEM to the first definite IEDs.ResultsA total of 241 patients were examined, including 191 with focal-onset epilepsy and 50 with generalized epilepsy. In individuals with focal-onset epilepsy, the median latency to the first IED was 63.0 min (IQR 19.0–299.0 min), as compared to 30.0 min (IQR 12.5–62.0 min) in patients with generalized epilepsy (p < 0.001). The latency to the first IED is significantly related to the age of seizure onset (HR = 0.988, p = 0.049), the interval between last seizure and VEM (HR = 0.998, p = 0.013). But it is not correlated with seizure frequency, gender and age.ConclusionsIEDs were discovered during 24-h EEG monitoring in 222/241(92.1%) of the epilepsy patients that were included. Compared to focal-onset epilepsy, generalized epilepsy demonstrated a much shorter latency to IED. Patients with late-onset epilepsy or those without recent episodes may require longer EEG monitoring periods.

Cenobamate in the management of focal-onset epilepsy in adults – practical considerations for daily practice

Cenobamate in the management of focal-onset epilepsy in adults – practical considerations for daily practice

Implementation of a 7T Epilepsy Task Force consensus imaging protocol for routine presurgical epilepsy work-up: effect on diagnostic yield and lesion delineation

ObjectiveRecently, the 7 Tesla (7 T) Epilepsy Task Force published recommendations for 7 T magnetic resonance imaging (MRI) in patients with pharmaco-resistant focal epilepsy in pre-surgical evaluation. The objective of this study was to implement and evaluate this consensus protocol with respect to both its practicability and its diagnostic value/potential lesion delineation surplus effect over 3 T MRI in the pre-surgical work-up of patients with pharmaco-resistant focal onset epilepsy.MethodsThe 7 T MRI protocol consisted of T1-weighted, T2-weighted, high-resolution-coronal T2-weighted, fluid-suppressed, fluid-and-white-matter-suppressed, and susceptibility-weighted imaging, with an overall duration of 50 min. Two neuroradiologists independently evaluated the ability of lesion identification, the detection confidence for these identified lesions, and the lesion border delineation at 7 T compared to 3 T MRI.ResultsOf 41 recruited patients > 12 years of age, 38 were successfully measured and analyzed. Mean detection confidence scores were non-significantly higher at 7 T (1.95 ± 0.84 out of 3 versus 1.64 ± 1.19 out of 3 at 3 T, p = 0.050). In 50% of epilepsy patients measured at 7 T, additional findings compared to 3 T MRI were observed. Furthermore, we found improved border delineation at 7 T in 88% of patients with 3 T-visible lesions. In 19% of 3 T MR-negative cases a new potential epileptogenic lesion was detected at 7 T.ConclusionsThe diagnostic yield was beneficial, but with 19% new 7 T over 3 T findings, not major. Our evaluation revealed epilepsy outcomes worse than ILAE Class 1 in two out of the four operated cases with new 7 T findings.

Atypical juvenile myoclonic epilepsy with structural brain abnormalities and cognitive impairment: A case report

Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy affecting 5–10% of epilepsy patients. Its exact cause remains unknown, but recent studies indicate frontal region involvement. It responds well to anticonvulsants but is often misdiagnosed with focal-onset epilepsy. We present a 9-year-old girl with myoclonic, absence, and generalized tonic-clonic seizures happening over three months. EEG revealed slow spike and wave complexes with generalized polyspikes, while brain MRI identified encephalomalacia cysts with right frontotemporal lobe hemiatrophy. Valproic acid treatment led to seizure-free status for one month. In conclusion, timely EEG and neuroimaging are pivotal in identifying structural abnormalities in JME patients with pronounced cognitive impairment, enabling tailored treatment and better outcomes.

Clinical outcomes following responsive neurostimulation implantation: a single center experience.

Responsive neurostimulation (RNS) is an implantable device for persons with medically refractory focal-onset epilepsy. We report a single-center experience for RNS outcomes with special focus on stereoelectroencephalography (sEEG) for seizure onset localization. We performed retrospective review of patients with drug resistant focal epilepsy implanted with the RNS System for a minimum of six months between July 2014 and July 2019. Records were reviewed for demographic data, epilepsy duration, seizure frequency, number of prior antiepileptic drugs (AEDs), number of AEDs at RNS System implantation, prior epilepsy surgery or device use, previous seizure localization with sEEG, and RNS system information. Clinical response was defined as a 50% reduction in seizures. Differing response rates were calculated using Fisher Exact test. 30 patients met inclusion criteria. Seventeen (57%) underwent previous sEEG. Average clinical follow up was 3.0 years. Overall response rate was 70%. Median seizure reduction was 74.5%. Response rate was 82.3% for patients with sEEG compared to 53.8% without (p = 0.08); 37.5% for prior epilepsy surgery compared to 81.8% without (p = 0.02); 70% for mesial temporal onset; 50% for previous vagal nerve stimulator compared to 77.3% without (p = 0.13). Our response rates match or surpass outcome metrics of previous studies. Although limited by small study size, subpopulation analyses show positive response rates in patients with previous sEEG versus no sEEG and in temporal versus extratemporal pathology. Additional research is needed to evaluate efficacy of RNS in patients with previous epilepsy surgery, and utility of sEEG in this population.

Increasing challenges to trial recruitment and conduct over time.

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

Efficacy and tolerability of immediate switch from sodium channel blockers to Lacosamide

Lacosamide (LCM) is a new-generation anti-seizure medication approved for monotherapy and add-on therapy for focal-onset epilepsy. It has novel pharmacodynamics and favorable pharmacokinetic qualities with good clinical response. This study aims to evaluate the effectiveness and tolerability of LCM when used in the immediate switch from sodium channel blockers in patients with focal-onset and generalized-onset epilepsies. This retrospective, multicenter observational study was conducted with adult patients who received LCM as mono- or polytherapy through immediate switch with 6 to 52 months follow-up. The clinical data obtained during the follow-up period were analyzed to assess retention rate, seizure freedom, more than 50% seizure reduction, and adverse effects. A total of 32 patients (eight females, 24 males) with a median age of 49.75 (range, 23–86) years, median age at epilepsy onset of 32.58 (range, 0.5–85) years, and median epilepsy duration of 17.17 (range, 1–46) years were included in this study. Seizure frequency was between 1 and 90 in the past 6 months. Seven (21.9%) of the patients had structural brain lesions and 27 (84.4%) of the patients had EEG abnormalities. The adverse effects leading to switching were hyponatremia, rash, elevated liver enzymes, pain, and erectile dysfunction. At 14.34 (range, 6–52) months follow-up, 30 (93.75%) patients in total retained LCM, 20 (66.7%) of them were seizure-free, and 13 were on LCM monotherapy. Responder rate was 81.25%. Eight (25%) of the patients experienced adverse effects after the immediate switch. One patient with generalized-onset epilepsy needed to quit LCM due to an increase in seizures. Seizure frequency did not change in three patients in the focal-onset group. Immediate switch to LCM showed favorable outcomes with a significant reduction in seizure frequency, high retention rates, and tolerable adverse effect profiles in both focal-onset and generalized-onset seizures.

Arousal deregulation in the co-shaping of neuropsychological dysfunction in frontal and mesial temporal lobe epilepsy

ObjectiveOur work aims to investigate the role of physiological arousal in the expression of neuropsychological deficits in frontal lobe epilepsy (FLE) and mesial temporal lobe epilepsy (mTLE), by drawing on the Lurian theory of brain function. MethodsFor this study a total of 43 patients with focal onset epilepsy has been taken; twenty-four patients with FLE, 19 patients with mTLE and 26 healthy controls, all matched for age and education. Participants underwent a comprehensive neuropsychological assessment including various cognitive domains, such as attention, episodic memory, speed of information processing, response inhibition and mental flexibility, working memory, verbal fluency (phonological & semantic). ResultsThere were no significant differences between FLE and mTLE patients in terms of neuropsychological performance. However, both FLE and mTLE patients showed significantly worse performance in several cognitive domains than HCs. The results seem to support our hypothesis that aberrant physiological arousal, as reflected in patients’ worse performance in vigilance and attention, response inhibition, and processing speed, along with other disease-specific variables, may co-determine neuropsychological dysfunction and/or impairment in both FLE and mTLE. ConclusionIdentifying a differential arousal-related neuropsychological affection in FLE and mTLE, among the known deleterious effects of the functional deficit zone and other disease-related variables, may further our understanding of the underlying cognitive-pathophysiological mechanisms in focal epilepsy syndromes.

Equipotency of lacosamide to levetiracetam in new onset focal epilepsy: A randomized controlled trial.

Levetiracetam (LEV) is a well-established broad spectrum antiseizure medication (ASM) effective in focal, generalized, and myoclonic seizures whereas lacosamide (LCM) is a comparatively newer ASM currently approved only as an add-on agent in focal seizures. The aim of the study was to assess the efficacy and the tolerability of oral LCM as monotherapy in adult people with epilepsy (PWE) with new onset focal onset epilepsy compared with those receiving LEV. In this open-label single-center non-inferiority trial, PWE aged between 16 and 65 years suffering from new onset focal seizures, with or without secondary generalization were put on LCM monotherapy or LEV monotherapy. Data regarding demographic characteristics, seizure type and etiology, LCM and LEV daily dose, seizure frequency at baseline and at 6 months of follow-up, and seizure freedom rates were recorded. Thirty-five PWE on LCM (24 males), their mean age: 38.20 ± 16.62 years and 35 PWE on LEV (25 males, mean age: 38.91 ± 17.13 years) were enrolled. The most common type of seizure observed was focal to bilateral tonic-clonic seizure >70% followed by focal impaired awareness seizure and focal awareness seizure. Structural epilepsy was found in 21 among LCM group and 22 of LEV group. In the LCM group, the seizure frequency decreased from 3.33 ± 1.88 to 0.85 ± 1.09 (P = 0.001) at 6 months and from 3.61 ± 3.12 to 0.94 ± 1.24 (P = 0.001) in LEV group, intergroup difference (P = 0.74). At 6-month follow-up period, 78.9% in LCM arm and 87.9% in the LEV arm had experienced a 50% of reduction in seizure frequency while seizure freedom was attained in 43.3% of PWE in both the arms (P = 1). The most common treatment emergent adverse effects in the LCM group were fatiguability, dyspepsia, headache, and dizziness, while in the LEV group; somnolence and behavioral abnormality. Treatment with LCM met the non-inferiority criteria when compared with LEV. Therefore, it might be useful as first-line monotherapy for adults with newly diagnosed focal epilepsy.

ID: 208400 Current Trends in Responsive Neurostimulation: A National Inpatient Sample Analysis

Responsive neurostimulation (RNS) has been used to treat adults with medically refractory focal onset epilepsy with 1 to 2 seizure foci since its FDA approval in 2013.1,2 Due to its effectiveness and favorable safety profile, it is utilized for epilepsy in adults and off-label in pediatric populations.3,4 In this study, we analyze current trends in utilization of RNS therapy.

Investigation of changes in MDH enzyme activity in epilepsy

Aims: Epilepsy is one of the most common neurological diseases. It is classified into three groups: focal onset, generalized onset and unclassifiable. A seizure type is difficult to determine. The malate dehydrogenase (MDH) enzyme has a critical role in the excitability of the brain, and it has been reported that recurrent seizures are seen when its regulation is disturbed. We investigated the contribution of MDH enzyme levels as a biomarker to seizure classification. Methods: Our study was conducted prospectively by patients who were admitted to the emergency department of our hospital within a six-month period. Included in the study were 65 patients diagnosed with epilepsy, according to the International League Against Epilepsy (ILAE) classification. The patients were divided into two groups according to seizure type: focal onset and generalized onset. They were compared in terms of enzyme activity. Results: The MDH value was 47.56 ± 38.65 in patients with focal-onset epilepsy and 109.76 ± 128.44 in patients with generalized-onset epilepsy. Conclusion: Our results reveal the potential of MDH as a biomarker that can be used in epilepsy. In addition, the statistically significant difference between focal-onset and generalized-onset epilepsy indicates that it can be a usable biomarker in seizure classification

Quality of life in people with epilepsy: beyond seizures

People with epilepsy have multiple barriers to recovery: access to medication, comorbidities and social problems. The aim of this study is to determine psychosocial factors associated with the perception of quality of life in people with epilepsy in the department of Bolivar, Colombia, in the year 2022. Descriptive cross-sectional study, correlational, with a sample stratified with a margin of error of 5%, according to the calculation of the average number of people treated for epilepsy in Colombia. 174 people participated with a mean age of 39.55 years, 50% men and 50% women. An instrument was used that determined sociodemographic data, quality of life (Quality of Life in Epilepsy Inventory-10), adherence to treatment (Morisky test), self-care behaviors, perception of disability and provision of health services. All the instruments showed a Cronbach's Alpha greater than 0.686 for this population. 21.3% had focal onset epilepsy; 41% with generalized epilepsy without focal onset; 18.4% with focal onset that generalized; 12.6% did not know their type of epilepsy; and 6.3% reported that they were not informed about their type of epilepsy. Based on correlations, an explanatory model of quality of life is shown, with pillars such as drug adherence, self-care habits, time without seizures, and perceived disability. Although time without seizures is a fundamental element in recovery, living conditions and mental health problems are key elements to achieve a better quality of life in epilepsy.

Isobolographic analysis of adjunct antiseizure activity of the FDA-approved cannabidiol with neurosteroids and benzodiazepines in adult refractory focal onset epilepsy

Epilepsy is a serious neurological disorder associated with recurrent and unpredictable seizures and extensive neuropsychiatric comorbidities. There is no cure for epilepsy, and over one third of epileptic patients have been diagnosed with drug-refractory epilepsy, indicating the critical need for novel antiseizure medications (ASMs). Cannabidiol (CBD) has been shown to decrease seizures in pediatric epilepsies, such as Dravet and Lennox-Gastaut syndromes; however, it has not been rigorously tested for adult seizures or in models of refractory focal epilepsy. Although the exact mechanism is unknown, it is likely to act in a way that is unique to certain GABA-A receptor-modulating drugs, such as neurosteroids and benzodiazepines. In this study, we sought to determine the adjunct antiseizure activity of a clinical CBD product in an adult 6-Hz model of focal refractory epilepsy. CBD was evaluated alone in both a dose-response and time-course manner and in an adjunct combination with two ASMs ganaxolone (neurosteroid) and midazolam (benzodiazepine) against 6-Hz-induced refractory focal onset, generalized seizures. In pharmacological studies, CBD produced dose-dependent protection against seizures (ED50, 53 mg/kg, i.p.) without any side effects. CBD significantly reduced both electrographic activity and behavioral ictal responses with no apparent sex differences. CBD was evaluated in an isobologram design in conjunction with ganaxolone or midazolam at three standard ratios (1:1, 1:3, 3:1). Isobolographic analysis shows the combination regimens of CBD + ganaxolone and CBD + midazolam exerted combination index of 0.313 and 0.164, indicating strong synergism for seizure protection, with little to no toxicity. Together, these results demonstrate the therapeutic potential of CBD monotherapy and as an adjunct therapy for adult focal refractory epilepsy in combination with GABAergic ASMs.

Effectiveness and safety of perampanel as adjunctive therapy among Chinese patients with focal-onset epilepsy: A real-world prospective observational study

ObjectivePerampanel (PER) has previously been shown to be effective and tolerable when used as an adjunctive therapy for patients with focal-onset seizures (FOS). This study aimed to evaluate the effect of PER as adjunctive therapy for patients with FOS in the Chinese population under real-world conditions for 1 year. MethodsA prospective, single-center, 1-year observational study was conducted at Huashan Hospital, enrolling both under age (≥4 years old) and adult patients with FOS. Response to PER was assessed at 3-, 6-, and 12-month checkpoints by analyzing the 50 % responder rate, the seizure-free rate, and reduction in seizure frequency. ResultsOne hundred and eight patients (mean age: 26.6 years, 56.5 % males) with FOS were included, with seventy-six patients finishing the 1-year follow-up (retention rate: 70.4 %, mean PER dose: 4.3 mg/day). The seizure frequency was reduced significantly at 3, 6, and 12 months relative to baseline (p < 0.001 for each seizure type). At 12 months, the responder rate was 65.8 %, and the seizure-free rate was 39.5 %. A significantly higher responder rate was found in patients with focal to bilateral tonic–clonic seizures (p = 0.024), among which the percentage of patients with sleep-related epilepsy was significantly high (p = 0.045). Responders had a lower number of concomitant anti-seizure medications (ASMs) than the non-responders (p = 0.009). Drug-related adverse events (AEs) were reported in 37 % of patients, mostly mild or moderate, and the patients who experienced AEs had a higher daily dose of PER than those who did not (p = 0.026). ConclusionPerampanel, an add-on therapy for focal-onset seizures, was found to be effective and tolerable in Chinese patients at 12 months.