Median Duration Of Epilepsy Research Articles

Perampanel for the treatment of Asian people with epilepsy: Real-world evidence from the PERMIT extension study

This post-hoc analysis of the PERMIT Extension study compared the effectiveness and safety/tolerability of perampanel (PER) between Asian and non-Asian participants. Retention rates, adverse events (AEs), seizure frequency, responder rate (≥50% seizure frequency reduction), and seizure freedom rate (no seizures since at least the prior visit) were assessed. Retention was assessed after 3, 6 and 12 months. Effectiveness assessments were evaluated at 3, 6 and 12 months and the last visit by seizure type (total, focal and generalised). PERMIT Extension included 730 Asian and 1662 non-Asian individuals. Significant differences in demographic/baseline characteristics were reported for the Asian versus non-Asian subgroups including higher median age at epilepsy onset, longer median duration of epilepsy, higher mean number of previous and concomitant ASMs and lower mean monthly seizure frequency (total, focal and generalised). Retention rates were similar between the two subgroups at 3 and 12 months, but significantly lower in the Asian versus non-Asian subgroup at 6 months (65.6% vs. 71.8%; p = 0.004). At last visit, seizure freedom rate was significantly higher in the Asian versus non-Asian for total (35.9% vs. 25.4%; p = 0.001) and focal seizures (32.4% vs. 18.9%; p = 0.001) as was responder rate for both total (63.9% vs. 52.3%; p = 0.001) and focal seizures (62.2% vs. 44.7%; p < 0.001). Seizure freedom and responder rates for generalised seizures were similar between the two subgroups at the last visit. Rates of AEs were similar between the two subgroups (Asian, 47.6%; non-Asian, 45.4%). PER was effective and generally well-tolerated in Asian and non-Asian individuals.

Treatment simplification to optimize cenobamate effectiveness and tolerability: A real-world retrospective study in Spain.

This study aimed to explore the impact of co-antiseizure medication (co-ASM) optimization on the effectiveness and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy in a real-world setting. This unicentric, retrospective, observational study included adults with focal-onset seizures who had received ≥2 previous ASMs. The main effectiveness endpoints included responder rates and seizure frequency reduction at 3, 6, and 12-month visits. The number of co-ASMs and defined daily dose (DDD) were analyzed at every visit. Safety endpoints included adverse drug reactions (ADRs). Thirty-four patients with a median epilepsy duration of 22 years and a median of 15.5 seizures/month were analyzed. The median number of prior ASMs was 12, and the mean number of co-ASMs was 2.9 (SD 1). There was a reduction in seizure frequency/month from baseline to the last visit (p < 0.0001). Between baseline and the end of the study, the mean number of co-ASMs in the per-protocol (PP) population was reduced from 2.9 to 1.6 (p < 0.0001), and DDD was reduced from 3.6 to 1.4 (p < 0.0001). Sodium channel blockers (carbamazepine and lacosamide) and GABAergic drugs (clobazam) were the agents with the most significant reductions in DDD after 12 months. The percentage of patients in the PP population with ≥3 co-ASMs was reduced from 61.8% at baseline to 14.3% at 12 months; 1 patient was receiving CNB as monotherapy at the last visit. At the last visit, 85.7% of the PP population were ≥50% responders, and 33.3% were seizure-free. The percentage of patients with ADRs in the PP population was 71.9% at 3 months and 52.3% at 12 months. Following rational polytherapy, optimization of co-ASM management during CNB treatment allowed high seizure freedom rates despite meaningful reductions in co-medication, while also achieving both good tolerability and patient satisfaction scores in a highly drug-resistant population. Many patients with epilepsy still have seizures, even after being treated with several different epilepsy drugs. In this study of 34 patients from a Spanish clinic, we show that the epilepsy drug cenobamate can reduce the number of seizures in these patients, even after many other epilepsy drugs have failed. We also show that patients treated with cenobamate can reduce the dose or even stop taking certain other epilepsy drugs. This allows them to simplify their treatment and reduce adverse effects while still keeping control of their epilepsy.

Sociodemographic and Clinical Characteristics of Persons with Epilepsy Attending an Epilepsy Clinic of a Tertiary Hospital in Bangladesh

Background: Epilepsy is a common neurological disorder found in all societies. It is seen that the relative frequency of various clinically important characteristics is different in persons with epilepsy (PWE) living in different geographical areas. The purpose of this study was to describe the sociodemographic and clinical characteristics of a cohort of patients with epilepsy from an Epilepsy Clinic of a tertiary hospital in Bangladesh. Methods: This cross-sectional study was conducted in the Department of Neurology at Rangpur Medical College Hospital, Rangpur, Bangladesh, from July 2022 to June 2023. The patients were recruited from the epilepsy clinic. A structured questionnaire was designed to collect relevant information by interviewing the consecutive PWEs. Results: A total of 252 PWEs were recruited, of which 134(53.2%) were male. Most [200(79.4%)] of them were young (age group 0 to 29 years) and had generalized seizures 147(58.3%). The median age of the 1st seizure was 11 years (range 0.5-73.0), and the median duration of epilepsy was 5.0(0-35) years in the present study. EEG, CT scan, and MRI could be done in 200(79.4%), 128(50.8%), and 68(27%, respectively. Among them, 24.2%(61), 10.7%(27), and 11.1%(28) patients had different types of abnormalities on EEG, CT scan, and MRI, respectively. A family history of seizures was present in 20(7.9%) patients. Sixteen patients(6.3%) were not getting any AEDs, 63.1% and 30.6% were on single and multiple AEDs, respectively. Sixty-five (25.8%) patients reported stopping the drug without any medical consultation. Forgetfulness was the most reported (21, 33.8%) reason for stopping drugs, followed by the misconception that the disease was cured (14, 21.5%), lack of time to buy pills (12, 18.5%), and no money to buy (9, 13.8%). Seventy-seven reported having two or more continuous seizures despite taking AEDs regularly. Conclusions: Present study documented some treatment gap and non-adherence to medication in PWE. PWE should be adequately advised about the disease and the effects of drug non-compliance. J Rang Med Col. March 2024; Vol. 9, No. 1: 44-49

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.

Sudden unexpected death in epilepsy during cenobamate clinical development.

We assessed mortality, sudden unexpected death in epilepsy (SUDEP), and standardized mortality ratio (SMR) among adults treated with cenobamate during the cenobamate clinical development program. We retrospectively analyzed deaths among all adults with uncontrolled focal (focal to bilateral tonic-clonic [FBTC], focal impaired awareness, focal aware) or primary generalized tonic-clonic (PGTC) seizures who received ≥1 dose of adjunctive cenobamate in completed and ongoing phase 2 and 3 clinical studies. In patients with focal seizures from completed studies, median baseline seizure frequencies ranged from 2.8 to 11 seizures per 28 days and median epilepsy duration ranged from 20 to 24 years. Total person-years included all days a patient received cenobamate during completed studies or up to June 1, 2022 for ongoing studies. All deaths were evaluated by two epileptologists. All-cause mortality and SUDEP rates were expressed per 1000 person-years. A total of 2132 patients (n=2018 focal epilepsy; n=114 idiopathic generalized epilepsy) were exposed to cenobamate for 5693 person-years. Approximately 60% of patients with focal seizures and all patients in the PGTC study had tonic-clonic seizures. A total of 23 deaths occurred (all in patients with focal epilepsy), for an all-cause mortality rate of 4.0 per 1000 person-years. Five cases of definite or probable SUDEP were identified, for a rate of 0.88 per 1000 person-years. Of the 23 overall deaths, 22 patients (96%) had FBTC seizures, and all 5 of the SUDEP patients had a history of FBTC seizures. The duration of exposure to cenobamate for patients with SUDEP ranged from 130-620 days. The SMR among cenobamate-treated patients in completed studies (5515 person-years of follow-up) was 1.32 (95% CI 0.84-2.0), which was not significantly different from the general population. These data suggest that effective long-term medical treatment with cenobamate may reduce excess mortality associated with epilepsy.

Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program.

This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP). This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness. In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation.

Responsive Neurostimulation for the Treatment of Children With Drug-Resistant Epilepsy in Tuberous Sclerosis Complex

BackgroundTo review seizure outcomes in children with tuberous sclerosis complex (TSC) and drug-resistant epilepsy (DRE) treated with the responsive neurostimulation (RNS) System. MethodsWe retrospectively reviewed children (<21 years old) with TSC implanted with the RNS System at Texas Children's Hospital between July 2016 and May 2022. ResultsFive patients meeting the search criteria were identified (all female). The median age of the RNS implantation was 13 years (range: 5 to 20 years). The median epilepsy duration before the RNS implantation was 13 years (range: 5 to 20 years). Surgeries before RNS implantation included vagus nerve stimulator placement (n = 2), left parietal resection (n = 1), and corpus callosotomy (n = 1). The median number of antiseizure medications tried before RNS was 8 (range: 5 to 12). The rationale for the RNS System implantation included seizure onset in eloquent cortex (n = 3) and multifocal seizures (n = 2). The maximum current density for each patient ranged between 1.8 and 3.5 μC/cm2, with an average daily stimulation of 2240 (range: 400 to 4200). There was an 86% median seizure reduction (range 0% to 99%) at a median follow-up duration of 25 months (range: 17 to 25 months). No patient experienced implantation or stimulation-related complications. ConclusionsWe observed a favorable improvement in seizure frequency in pediatric patients with DRE secondary to TSC treated with the RNS System. The RNS System may be a safe and effective treatment for DRE in children with TSC.

Functional Anterior Temporal Lobectomy for Temporal Lobe Epilepsy: A Novel, Alternative, and Less Invasive Therapy.

Anterior temporal lobectomy is the most effective treatment for intractable temporal lobe epilepsy (TLE). However, patients are reluctant to choose this surgery for fear of risks after large frontotemporal craniotomy, and epileptologists likewise have a cautious attitude because of surgical trauma. Functional anterior temporal lobectomy (FATL) is a minimally invasive surgery procedure for addressing the above concerns. To report preliminary data on this procedure and its safety and efficacy for treating TLE. This consecutive case series study was conducted between October 2020 and September 2021. Patients with TLE underwent FATL by minicraniotomy with a diameter of 3 cm. Surgery duration, postoperative complications, and seizure control are described herein. Seizure outcomes were classified using Engel classifications. A total of 25 patients undergoing FATL for TLE were enrolled. The median epilepsy duration was 8 years. The median surgery duration was 165 min. The median blood loss was 100 mL. The median postoperative hospital stay was 8 days. No deaths occurred after surgery. Only 1 patient presented with a cerebrospinal fluid disorder that was successfully treated using a ventriculoperitoneal shunt. At the last follow-up, 23 patients (92%) were seizure-free (Engel-Ia), 1 patient remained substantially improved (Engel-II), and 1 patient obtained worthwhile seizure reduction (Engel-III). Our pilot study suggests that FATL is a viable surgical therapy for TLE. This method has the advantages of minimal invasiveness and high seizure-free rate. A controlled trial is warranted to verify the efficacy and safety of FATL comparing with anterior temporal lobectomy.

The long-term surgical outcomes of low-grade epilepsy-associated neuroepithelial tumors.

This study aimed to evaluate the surgical outcomes and relevant prognostic factors in patients with low-grade epilepsy-associated neuroepithelial tumors (LEAT) and, especially, to develop a scoring system to predict postoperative seizure outcomes. The clinical data of patients who underwent epilepsy surgery for LEAT were retrospectively studied. The surgical outcomes of seizure and neurological statuses in patients were evaluated using Engel classification and modified Rankin Scale (mRS) scoring, respectively. A scoring system of seizure outcomes was constructed based on the weight of the β-coefficient estimate of each predictor in the final multivariate predicting model of seizure outcomes. Of the 287 patients (106 female) enrolled, the median age was 19 years at surgery and 10 years at seizure onset, with a median duration of epilepsy of 60months. Among 258 patients who were followed up for at least 12months, 215 (83.3%) patients had a favorable seizure outcome (Engel class I) after surgery, and 43 (16.7%) patients had an unfavorable seizure outcome; longer duration of epilepsy, discordant magnetoencephalography (MEG) findings, and acute postoperative seizures were significantly included in the scoring system to predict unfavorable seizure outcomes, and in the scoring system, accumulated scoring of 0-19 scores was recorded, which were finally grouped into three risk levels: low risk (risk < 30%), medium risk (30% ≤ risk < 70%), and high risk (risk ≥ 70%). In addition, favorable neurological outcomes (mRS score 0-1) were recorded in 187 (72.5%) patients, while unfavorable neurological outcomes were recorded in 71 (27.5%) patients, which were significantly related to poor seizure control, older age at surgery, and longer duration of epilepsy and hospitalization time. The long-term surgical outcomes of LEAT after surgery were satisfactory. A scoring system for predicting unfavorable seizure outcomes with different risk levels was developed, which could partly guide clinical treatments of LEAT.

Postsurgical seizure outcome in temporal lobe epilepsy patients with normal or subtle, nonspecific MRI findings.

The authors' objective was to report postsurgical seizure outcome of temporal lobe epilepsy (TLE) patients with normal or subtle, nonspecific MRI findings and to identify prognostic factors related to seizure control after surgery. This was a retrospective study of patients who underwent surgery from 1999 to 2014 at two comprehensive epilepsy centers. Patients with a clear MRI lesion according to team discussion and consensus were excluded. Presurgical information, surgery details, pathological data, and postsurgical outcomes were retrospectively collected from medical charts. Multiple logistic regression analysis was used to assess the effect of clinical, surgical, and neuroimaging factors on the probability of Engel class I (favorable) versus class II-IV (unfavorable) outcome at last follow-up. The authors included 73 patients (59% were female; median age at surgery 35.9 years) who underwent operations after a median duration of epilepsy of 13 years. The median follow-up after surgery was 30.6 months. At latest follow-up, 44% of patients had Engel class I outcome. Favorable prognostic factors were focal nonmotor aware seizures and unilateral or no spikes on interictal scalp EEG. Favorable outcome can be achieved in a good proportion of TLE patients with normal or subtle, nonspecific MRI findings, particularly when presurgical investigation suggests a rather circumscribed generator. Presurgical factors such as the presence of focal nonmotor aware seizures and unilateral or no spikes on interictal EEG may indicate a higher probability of seizure freedom.

Outcomes of cingulate epilepsy surgery: insights from an institutional and patient-level systematic review and meta-analysis.

Due to their deep and medial location, range of seizure semiologies, and poor localization on ictal electroencephalography (EEG), cingulate gyrus seizures can be difficult to diagnose and treat. The aim of this study was to review the available evidence on postoperative outcomes after cingulate epilepsy surgery. A comprehensive literature search of the PubMed/MEDLINE, Ovid Embase, Ovid Scopus, and Cochrane Library databases was conducted to identify studies that investigated postoperative outcomes of patients with cingulate epilepsy. Seizure freedom at the last follow-up (at least 12 months) was the primary endpoint. The literature search was supplemented by the authors' institutional series (4 patients). Twenty-one studies were identified, yielding a total of 105 patients (68 with lesional epilepsy [65%]). Median age at surgery was 23 years, and 56% of patients were male. Median epilepsy duration was 7.5 years. Invasive EEG recording was performed on 69% of patients (53% of patients with lesional epilepsy and 97% of those with nonlesional epilepsy, p < 0.001). The most commonly resected region was the anterior cingulate (55%), followed by the posterior (17%) and middle (14%) cingulate. Lesionectomy alone was performed in 9% of patients. Additional extracingulate treatment was performed in 54% of patients (53% of patients with lesional epilepsy vs 57% of those with nonlesional epilepsy, p = 0.87). The most common pathology was cortical dysplasia (54%), followed by low-grade neoplasm (29%) and gliosis (8%). Seizure freedom was noted in 72% of patients (median follow-up 24 months). A neurological deficit was noted in 27% of patients (24% had temporary deficit), with the most common deficit being motor weakness (13%) followed by supplementary motor area syndrome (9.5%). Univariate survival analysis revealed significantly greater probability of seizure freedom in patients with lesional epilepsy (p = 0.015, log-rank test). Surgical treatment of drug-resistant focal epilepsy originating from the cingulate gyrus is safe, leads to low rates of permanent adverse effects, and leads to high rates of long-term seizure freedom in carefully selected patients. These data may serve as a benchmark for surgical counseling of patients with cingulate epilepsy.

Evaluation of one-year effectiveness of clobazam as an add-on therapy to anticonvulsant monotherapy in participants with epilepsy having uncontrolled seizure episodes: An Indian experience

ObjectivesTo prospectively study the effectiveness and safety of clobazam as an add-on therapy in patients with epilepsy whose seizures are not adequately controlled with antiseizure medicine (ASM) monotherapy. MethodsWe conducted a prospective, observational study at 28 neurology outpatient clinics in India from June 2017 to October 2019. Consecutive patients with epilepsy (older than 3 years) with inadequate seizure control with ASM monotherapy were initiated on clobazam. Patients were followed up at 1, 3, 6, 9, and 12 months. Seizure control and adverse events were assessed through personal interviews and seizure diaries. ResultsOut of 475 eligible patients, data of 429 patients (men: 65.5%) were evaluated (46 excluded due to protocol deviations). The median age was 25 (range, 3–80 years) years and the median duration of epilepsy was 3 (0.1–30) years. The majority of patients had focal epilepsy (55.0%) and genetic generalized epilepsy (40.1%). The one-year follow-up was completed by 380 (88.5%) patients. At one-year follow-up, 317 (83.4%; N = 380) patients in the study remained seizure free. These 317 patients who were seizure free at 12 months comprised 73.9% of the evaluable population (N = 429). In 98.8% of patients, the primary reason for adding clobazam was inadequate control of seizures with treatment. During one-year follow-up, a total of 113 (22.6%) patients experienced at least one adverse event which included 103 (20.6%) patients who experienced 386 episodes of seizures. ConclusionThe study provides preliminary evidence that clobazam is effective and well-tolerated as add-on therapy for a period of one year among patients with epilepsy inadequately stabilized with monotherapy. Trial registration numberCTRI/2017/12/010906.

Insular epilepsy surgery: lessons learned from institutional review and patient-level meta-analysis.

Insular lobe epilepsy is a challenging condition to diagnose and treat. Due to anatomical intricacy and proximity to eloquent brain regions, resection of epileptic foci in that region can be associated with significant postoperative morbidity. The aim of this study was to review available evidence on postoperative outcomes following insular epilepsy surgery. A comprehensive literature search (PubMed/MEDLINE, Scopus, Cochrane) was conducted for studies investigating the postoperative outcomes for seizures originating in the insula. Seizure freedom at last follow-up (at least 12 months) comprised the primary endpoint. The authors also present their institutional experience with 8 patients (4 pediatric, 4 adult). A total of 19 studies with 204 cases (90 pediatric, 114 adult) were identified. The median age at surgery was 23 years, and 48% were males. The median epilepsy duration was 8 years, and 17% of patients had undergone prior epilepsy surgery. Epilepsy was lesional in 67%. The most common approach was transsylvian (60%). The most commonly resected area was the anterior insular region (n = 42, 21%), whereas radical insulectomy was performed in 13% of cases (n = 27). The most common pathology was cortical dysplasia (n = 68, 51%), followed by low-grade neoplasm (n = 16, 12%). In the literature, seizure freedom was noted in 60% of pediatric and 69% of adult patients at a median follow-up of 29 months (75% and 50%, respectively, in the current series). A neurological deficit occurred in 43% of cases (10% permanent), with extremity paresis comprising the most common deficit (n = 35, 21%), followed by facial paresis (n = 32, 19%). Language deficits were more common in left-sided approaches (24% vs 2%, p < 0.001). Univariate analysis for seizure freedom revealed a significantly higher proportion of patients with lesional epilepsy among those with at least 12 months of follow-up (77% vs 59%, p = 0.032). These findings may serve as a benchmark when tailoring decision-making for insular epilepsy, and may assist surgeons in their preoperative discussions with patients. Although seizure freedom rates are quite high with insular epilepsy treatment, the associated morbidity needs to be weighed against the potential for seizure freedom.

Mammillary Body Atrophy in Temporal Lobe Epilepsy With Hippocampal Sclerosis.

We aimed to determine 1) the frequency of mammillary body (MB) atrophy in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS), 2) the clinical significance of MB atrophy, and 3) the association between MB atrophy and volume changes in other subcortical limbic structures. We enrolled 69 patients with pathologically confirmed TLE with HS, who underwent a standard anterior temporal lobectomy, as well as 40 healthy controls. We used the FreeSurfer deep-learning tool of U-Net to obtain the volumes of the subcortical limbic structures, including the MB, hypothalamus, basal forebrain, septal nuclei, fornix, and nucleus accumbens. MB atrophy was considered to be present when the MB volume was decreased relative to the healthy controls. MB atrophy was present in 18 (26.1%) of the 69 patients with TLE and HS. Among the clinical characteristics, the mean age at seizure onset was higher (25.5 vs. 15.9 years, p=0.027) and the median duration of epilepsy was shorter (149 vs. 295 months, p=0.003) in patients with than without MB atrophy. The basal forebrain (0.0185% vs. 0.0221%, p=0.004) and septal nuclei (0.0062% vs. 0.0075%, p=0.003) in the ipsilateral hemisphere of HS were smaller in the patients with MB atrophy. We observed ipsilateral MB atrophy in about one-quarter of patients with TLE and HS. The severity of subcortical limbic structure abnormalities was greater in patients without MB atrophy. These findings suggest that MB atrophy in TLE with HS is not rare, but it has little clinical significance.

MRI-guided stereotactic laser corpus callosotomy for epilepsy: distinct methods and outcomes.

Several small series have described stereotactic MRI-guided laser interstitial thermal therapy for partial callosotomy of astatic and generalized tonic-clonic (GTC) seizures, especially in association with Lennox-Gastaut syndrome. Larger case series and comparison of distinct stereotactic methods for stereotactic laser corpus callosotomy (SLCC), however, are currently lacking. The objective of this study was to report seizure outcomes in a series of adult patients with epilepsy following anterior, posterior, and complete SLCC procedures and to compare the results achieved with a frameless stereotactic surgical robot versus direct MRI guidance frames. The authors retrospectively reviewed sequential adult epilepsy surgery patients who underwent SLCC procedures at a single institution. They describe workflows, stereotactic errors, percentage disconnection, hospitalization durations, adverse events, and seizure outcomes after performing anterior, posterior, and complete SLCC procedures using a frameless stereotactic surgical robot versus direct MRI guidance platforms. Thirteen patients underwent 15 SLCC procedures. The median age at surgery was 29 years (range 20-49 years), the median duration of epilepsy was 21 years (range 9-48 years), and median postablation follow-up was 20 months (range 4-44 months). Ten patients underwent anterior SLCC with a median 73% (range 33%-80%) midsagittal length of callosum acutely ablated. Following anterior SLCC, 6 of 10 patients achieved meaningful (> 50%) reduction of target seizures. Four patients underwent posterior (completion) SLCC following prior anterior callosotomy, and 1 patient underwent complete SLCC as a single procedure; 3 of these 5 patients experienced meaningful reduction of target seizures. Overall, 8 of 10 patients in whom astatic seizures were targeted and treated by anterior and/or posterior SLCC experienced meaningful improvement. SLCC procedures with direct MRI guidance (n = 7) versus a frameless surgical robot (n = 8) yielded median radial accuracies of 1.1 mm (range 0.2-2.0 mm) versus 2.4 mm (range 0.6-6.1 mm; p = 0.0011). The most serious adverse event was a clinically significant intraparenchymal hemorrhage in a patient who underwent the robotic technique. This is the largest reported series of SLCC for epilepsy to date. SLCC provides seizure outcomes comparable to open surgery outcomes reported in the literature. Direct MRI guidance is more accurate, which has the potential to reduce the risks of SLCC. Methodological advancements and larger studies are needed.

Epilepsy duration is an independent factor for electrocardiographic changes in pediatric epilepsy.

ObjectiveCardiac alterations represent a potential epilepsy‐associated comorbidity. Whether cardiac changes occur as a function of epilepsy duration is not well understood. We sought to evaluate whether cardiac alterations represented a time‐dependent phenomenon in pediatric epilepsy.MethodsWe retrospectively followed pediatric epilepsy patients without preexisting cardiac conditions or ion channelopathies who had history of pediatric intensive care unit admission for convulsive seizures or status epilepticus between 4/2014 and 7/2017. All available 12‐lead electrocardiograms (ECGs) from these patients between 1/2006 and 5/2019 were included. We examined ECG studies for changes in rhythm; PR, QRS, or corrected QT intervals; QRS axis or morphology; ST segment; or T wave. Data were analyzed using multivariable models containing covariates associated with ECG changes or epilepsy duration from the univariate analyses.Results127 children with 323 ECGs were included in the analyses. The median epilepsy duration was 3.9 years (IQR 1.3‐8.4 years) at the time of an ECG study and a median of 2 ECGs (IQR 1‐3) per subject. The clinical encounters associated with ECGs ranged from well‐child visits to status epilepticus. We observed changes in 171 ECGs (53%), with 83 children (65%) had at least 1 ECG with alterations. In a multivariable logistic regression model adjusting for potentially confounding variables and accounting for clustering by patient, epilepsy duration was independently associated with altered ECGs for each year of epilepsy (OR: 1.1, 95% CI: 1.0‐1.2, P = .002). Extrapolating from this model, children with epilepsy durations of 10 and 15 years had 2.9 and 4.9 times the odds of having ECG changes, respectively.SignificanceCardiac alterations may become more common with increasing epilepsy duration in select pediatric epilepsy patients. Future studies are needed to determine the potential clinical implications and the generalizability of these observations.

Lacosamide as first add-on or conversion monotherapy: A retrospective real-life study

PurposeLacosamide (LCM), the R-enantiomer of 2-acetamido-N-benzyl-3-methoxypropionamide, is a newer approved antiseizure medication characterized by a novel pharmacodynamic and favorable pharmacokinetic profile that was approved as adjunctive treatment for adults with focal onset and focal to bilateral tonic-clonic seizures in 2008, and recently also for monotherapy. The aim of this study was to evaluate the effectiveness and tolerability of LCM as first add-on or conversion monotherapy in adult subjects with focal epilepsy. MethodsWe retrospectively included all adult patients who received LCM as first add-on regimen or as substitution monotherapy at least 12 months before starting the chart review, with a historical baseline of 6 months prior to day of the first administration of LCM. The choice of treatment was made independently by the epilepstologists, according to routine clinical practice. Clinical data were obtained at 3, 6, and 12 months after subjects started LCM and then analyzed to assess retention rate, seizure freedom, and adverse events (AE). ResultsA total of 101 patients (58 men) with a mean age of 44 years and a median epilepsy duration of 6.6 years (range 1–53) were included in the study. At 12 months 72 patients retained LCM, 54 (75%) of them were seizure free, 44 (81.5%) in monotherapy and 10 (18.5%) in add-on LCM treatment. Among all subjects, 31 (57.4%) were free from seizure under LCM monotherapy throughout the entire observation period. Thirty one out of 72 (43%) PwE who retained LCM at 12 months, were free from seizures throughout the entire observation period. The maintenance median dosage of LCM was 200 mg/day. Ten (10%) subjects reported mild to moderate AE, most commonly drowsiness and dizziness. No serious AE were documented. ConclusionsThis real-life study confirms that LCM is an effective and well tolerated treatment option as first add-on or conversion monotherapy for focal seizures.

Management and outcome of vagus nerve stimulator implantation: experience of an otolaryngeal/neuropediatric cooperation

ObjectiveVagus nerve stimulator (VNS) implantation is an established therapy for pharmacoresistant epilepsy that is not amenable to curative epilepsy surgery. Historically, VNS implantation has been performed by neurosurgeons, but otolaryngologist involvement is increasingly common. In this retrospective study, we aimed to evaluate the efficacy and safety of VNS implantation in children and adolescents from the otolaryngologists’ perspective.MethodsThis study included children and adolescents who had undergone VNS implantation at the study center between 2014 and 2018. Patient files were analyzed with regards to the durations of device implantation and hospitalization, postoperative complications, and clinical outcome, including seizure frequency, clinical global impression of improvement (CGI-I) score, and quality of life (QoL).ResultsA total of 73 children underwent VNS surgery. The median age at implantation was 9.3 ± 4.6 years, and median epilepsy duration before VNS surgery was 6 ± 4 years. Lennox–Gastaut syndrome was the most common syndrome diagnosis (62.3%), and structural abnormalities (49.3%) the most frequent etiology. Operation times ranged from 30 to 200 min, and median postoperative hospitalization length was 2 ± 0.9 days. No complications occurred, except for four revisions and two explantations due to local infections (2.7%). Among our patients, 76.7% were responders (≥ 50% reduction in seizure frequency), 72.1% showed improved CGI-I scores, and 18.6–60.5% exhibited considerable improvements in the QoL categories energy, emotional health, and cognitive functions.ConclusionOur results indicate that VNS implantation is a highly effective and safe treatment option for children and adolescents with AED-refractory epilepsies who are not candidates for curative epilepsy surgery.

Influence of COVID-19 pandemic on quality of life in patients with epilepsy – Follow-up study

ObjectiveTo perform a follow-up study of the quality of life in patients with epilepsy in the era of the COVID-19 crisis. MethodsTwo months before the first case of the COVID-19 in Serbia, we obtained the Serbian Version of Quality of Life Inventory for Epilepsy 31 (SVQOLIE-31) and Neurological Disorders Depression Inventory for Epilepsy scores (SVNDDI-E) for another study. We retested the same patients one year after in COVID-19 pandemic. In addition to SVQOLIE-31, and SVNDDI-E we used a generic questionnaire compiled from items related to the COVID-19. ResultsWe retested 97 out of 118 patients (82.2%) for the follow-up analysis. The average age was 36.1 ± 12.2 (range: 18–69), and 49 were women (50.5%). The median duration of epilepsy was 13 years (range: 1.5–48). The structural etiology of epilepsy was noted in 41 (42.3%), unknown etiology in 41 (42.3%), and genetic etiology in 15 (15.4%) patients. Fewer patients (27.8%) experienced at least one seizure three months before follow-up testing when compared to patients who experienced at least one seizure three months in initial testing (36.0%) (p = 0.15). All patients reported full compliance with anti-seizure medication in the follow-up. The SVQOLIE-31 score during the COVID-19 pandemic visit (64.5 ± 14.6) was significantly lower than the SVQOLIE-31 score before the pandemic (p < 0.001). The SVNDDI-E score during the COVID-19 pandemic (10.5 ± 3.5) was significantly higher than the SVNDDI-E score before it (p < 0.001). Multiple linear regression analyses revealed fear of seizures, and fear of a reduction in household income, significantly associated with SVQOLIE-31 and SVNDDI-E overall score. These variables accounted for 66% and 27% of the variance of SVQOLIE-31 and SVNDDI-E overall score. SignificanceLower quality of life, higher prevalence of depression, healthcare availability issues, and perceived fears during pandemic all suggest COVID-19 has negatively impacted lives of patients with epilepsy.

Efficacy of adjunctive cenobamate based on number of concomitant antiseizure medications, seizure frequency, and epilepsy duration at baseline: A post-hoc analysis of a randomized clinical study

BackgroundIn an 18-week, double-blind, placebo-controlled study (YKP3089C017; NCT01866111), cenobamate was effective for the treatment of focal-onset seizures. This post-hoc analysis examined the effects of baseline clinical features on the efficacy of adjunctive cenobamate during the study. MethodsAdults with uncontrolled focal seizures despite treatment with 1–3 antiepileptic drugs/antiseizure medications (AEDs/ASMs) were randomized 1:1:1:1 to placebo or cenobamate 100, 200, or 400 mg once daily. Median percent seizure frequency reduction/28 days and ≥50% responder rates were assessed during the 12-week maintenance phase (n = 397) by number of baseline (concomitant) ASMs (1, 2, >2), median baseline seizure frequency/28 days (≤9.5 vs >9.5), and median baseline duration of epilepsy (≤23 vs >23 years). ResultsFor patients taking 1 concomitant ASM, median percent seizure frequency reductions ranged from 44.7% to 86.0% for cenobamate-treated patients vs 24.1% for placebo; for 2 concomitant ASMs, reductions were 41.4–57.9% with cenobamate vs 33.3% for placebo; and for >2 concomitant ASMs, reductions were 41.5–67.4% with cenobamate vs 26.4% for placebo. The highest reductions occurred in the 200- and 400-mg/day cenobamate groups. For patients with baseline seizure frequency ≤9.5, the greatest reduction in median percent seizure frequency occurred in the 200-mg/day cenobamate group (66.5%); for patients with baseline seizure frequency >9.5 the greatest reduction occurred in the 400-mg/day cenobamate group (70.7%). Similar improvements were observed when assessed by median duration of epilepsy at baseline. For cenobamate-treated patients taking 1, 2, or >2 ASMs respectively, ≥50% responder rates of up to 66.7% (400 mg), 62.2% (200 mg), and 66.0% (400 mg) were observed, vs 20.0%, 29.3%, and 23.9% for placebo, respectively; 100% seizure reductions were observed in up to 25.0% (400 mg/day), 22.2% (400 mg/day), and 19.1% (400 mg/day) of cenobamate-treated patients, vs 0%, 0%, and 2.2% for placebo, respectively. Incidence of common (≥10%) central nervous system adverse events (dizziness, somnolence, fatigue, and diplopia) were highest in the >2 ASM group, but the rates were within the range reported in the primary study. ConclusionsClinically relevant reductions in seizure frequency including 100% seizure reductions occurred with adjunctive cenobamate regardless of number of concomitant ASMs, baseline seizure frequency, or disease duration. The greatest reductions occurred in the 200- and 400-mg/day groups.