Search

• Cenobamate was effective and safe in a cohort of patients with highly refractory focal epilepsy. • The percentage of hyper-responder patients (> 90% of seizure reduction or seizure-free) was exceptionally high. • The introduction of cenobamate allowed the reduction of other concomitant ASM, particularly other sodium channel blockers, maintaining effectivity and reducing adverse events. To determine the effectiveness and safety outcomes of cenobamate in a cohort of patients with highly refractory focal epilepsy in routine clinical practice. Observational, retrospective, phase 4 study on subjects receiving cenobamate in three Spanish centers. The primary endpoint was the retention rate at the last follow-up. The main secondary endpoints were the 50%-responder and seizure-free rates at three months and the last follow-up. Other secondary endpoints were Global Clinical Impressions-Improvement (CGI-I) scores and treatment-emergent adverse events (TEAEs). Fifty-one patients with highly refractory focal epilepsy with 24.7 years of disease evolution, ten previously tried ASM, and a 23.5% of previous epilepsy surgery were included. The retention rate at the last follow-up was 80.4%. The 50% responder rate in focal seizures at three months was 56.5% (median reduction per month 51%, 0–74.6; p < 0.0001) and in focal to bilateral tonic-clonic seizures was 63.6% (median reduction per month 89%, 0–100; p = 0.022). A total of 54.3% of subjects reported a reduction in the intensity of focal seizures, and 66% manifested clinically significant satisfaction. Cenobamate allowed a significant decrease in concomitant ASM, especially sodium channel blockers. TEAEs were reported in 43.1% of individuals, 85% of whom resolved or improved, with no new safety findings. In this analysis of patients with highly refractory focal epilepsy treated with cenobamate according to standard clinical practice, there was evidence of a high reduction in both seizure frequency and intensity, with a manageable safety profile. [ABSTRACT FROM AUTHOR]

MOGHE is defined as mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Approximately half of the patients with histopathologically confirmed MOGHE carry a brain somatic variant in the SLC35A2 gene encoding a UDP-galactose transporter. Previous research showed that D-galactose supplementation results in clinical improvement in patients with a congenital disorder of glycosylation due to germline variants in SLC35A2. We aimed to evaluate the effects of D-galactose supplementation in patients with histopathologically confirmed MOGHE, with uncontrolled seizures or cognitive impairment and epileptiform activity at the EEG after epilepsy surgery (NCT04833322). Patients were orally supplemented with D-galactose for 6 months in doses up to 1.5 g/kg/day and monitored for seizure frequency including 24-h video-EEG recording, cognition and behavioral scores, i.e., WISC, BRIEF-2, SNAP-IV, and SCQ, and quality of life measures, before and 6 months after treatment. Global response was defined by > 50% improvement of seizure frequency and/or cognition and behavior (clinical global impression of "much improved" or better). Twelve patients (aged 5–28 years) were included from three different centers. Neurosurgical tissue samples were available in all patients and revealed a brain somatic variant in SLC35A2 in six patients (non-present in the blood). After 6 months of supplementation, D-galactose was well tolerated with just two patients presenting abdominal discomfort, solved after dose spacing or reduction. There was a 50% reduction or higher of seizure frequency in 3/6 patients, with an improvement at EEG in 2/5 patients. One patient became seizure-free. An improvement of cognitive/behavioral features encompassing impulsivity (mean SNAP-IV − 3.19 [− 0.84; − 5.6]), social communication (mean SCQ − 2.08 [− 0.63; − 4.90]), and executive function (BRIEF-2 inhibit − 5.2 [− 1.23; − 9.2]) was observed. Global responder rate was 9/12 (6/6 in SLC35A2-positive). Our results suggest that supplementation with D-galactose in patients with MOGHE is safe and well tolerated and, although the efficacy data warrant larger studies, it might build a rationale for precision medicine after epilepsy surgery. [ABSTRACT FROM AUTHOR]

Epilepsy is a global disease with an unequal distribution. About 80% of the affected individuals reside in low and middle income countries. The incidence and prevalence of epilepsy in low income populations is higher than in the rest of the world, this is partly explained by some risk factors such as head trauma, perinatal injury and CNS infections, which are more common in poor regions, especially in rural areas. Epilepsy is considered a treatable condition with high rates of therapeutic response. About three fourths of patients achieve control of the disease with the use of antiepileptic drugs, however, despite this benign prognosis, over 75% of patients from low income populations do not receive treatment at all. The cultural beliefs, the inequity in the distribution of public health services, the inadequate supply of antiepileptic drugs, the low number of neurologists involved in the attention of epilepsy, and the social stigma, are the main reasons that increase the treatment gap and the burden of disease in low income populations with epilepsy. We conducted a narrative review regarding the epidemiology of epilepsy in low income populations by searching PubMed, EMBASE, Google Scholar and thoroughly examining relevant bibliographies. This review aims to summarize the main epidemiological aspects of epilepsy in LMIC, emphasizing on incidence, prevalence, socio-demographic profile, TG, social stigma and QoL. [ABSTRACT FROM AUTHOR]

Purpose The goal of this study is to report the efficacy and tolerability of lacosamide (LCM) monotherapy, as first-line and conversion regimens, in the treatment of patients with partial-onset seizures. Methods We retrospectively reviewed the charts of patients with focal epilepsy on LCM monotherapy from six centers in Spain. Efficacy and tolerability were evaluated in the overall group and in subgroups of patients who were naive to antiepileptic drug (AED) therapy (Group 1) and those who had previously been treated with AEDs (Group 2). Results Sixty-six patients were identified including 18 patients in Group 1 and 48 patients in Group 2. Patients were followed up for 0.5–54 months in monotherapy (mean 15.5 months). Forty-two (63.6%) patients remained seizure-free during all the follow-up. At 6 and 12 months, seizure-free rates were 77.6% and 72.3%, respectively. The drug was withdrawn in 10 (15%) patients (3 side effects, 6 lack of efficacy, 1 other reason). Fifteen (22.7%) patients reported mild to moderate side effects with the use of LCM. No differences were found between Groups 1 and 2 regarding efficacy outcomes or tolerability issues. Conclusions In our series more than two-thirds of the patients remained seizure-free on LCM monotherapy. Side effects were generally mild and led to discontinuation in only 3/66 (4.5%) patients. Our experience suggests that LCM monotherapy, either as first-line or after conversion, may be a valuable option for patients with focal epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: This retrospective study reports the early experience with lacosamide (LCM) as adjunctive therapy in Spanish patients with refractory focal epilepsy. Sixty patients (mean age 38.3 years, 54% women, mean epilepsy duration 27.2 years, mean seizure rate 9.7/month, and 28% with mainly nocturnal seizures) taking ≥2 antiepileptic drugs (mean 2.2) were included. LCM maintenance doses were 200, 300, 400, and 500mg/day in 31, 16, 10, and 3 patients, respectively. Patients were followed up for 13–24 months. Twenty-eight patients (47%) reported a ≥50% reduction in seizure frequency. A ≥50% reduction in seizure frequency was reported by 65% and 40% of patients in the nocturnal seizure and diurnal seizure subgroups, respectively (p >0.05). Of the 28 responders, 2 achieved stable periods of seizure freedom of 6 and 11 months after starting LCM. Twenty patients (33%) reported drug-related adverse events (AEs); the most common was dizziness (16 patients). LCM was withdrawn in 8 patients (13%). There were no serious AEs. These results support the efficacy and safety of adjunctive LCM in patients with partial-onset seizures. [Copyright &y& Elsevier]

Decades of research have increased the understanding of the contribution of the anterior temporal lobes (ATLs) to semantic cognition. Nonetheless, whether semantic processing of different types of information show a selective relationship with left and right ATLs, or whether semantic processing in the ATLs is independent of the modality of the input is currently unknown. There exists evidence supporting each of these alternatives. A fundamental objection to these findings is that they were obtained from studies with patients with brain damage affecting extensive regions, sometimes bilaterally. In the current study, we assessed a group of 38 temporal lobe epilepsy (TLE) patients with either left or right small epileptogenic lesions with a battery of commonly used semantic tasks that tested verbal and non-verbal semantic processing. We found that left TLE patients exhibited worse performance than controls on the verbal semantic tasks, as expected, but also on the non-verbal semantic task. On the other hand, performance of the right TLE group did not differ from controls on the non-verbal task, but was worse on a semantic fluency task. When performance between patient groups was compared, we found that left TLE not only did worse than right TLE on the naming task, but also on the non-verbal associative memory task. When considered together, current data do not support a strong view of input modality differences between left and right ATLs. Additionally, they provide evidence indicating that the left and right ATLs do not make similar contributions to a singular functional system for semantic representation. • Left ATL damage was associated with verbal and non-verbal semantic impairment. • Right ATL damage was not associated non-verbal semantic impairment. • Left and right ATLs do not contribute similarly to semantic representation system. • Input modality differences between left and right ATLs were not found. [ABSTRACT FROM AUTHOR]