Seizure Reduction Rate Research Articles

Decanoic acid-enriched ketogenic diet in refractory epilepsy

ObjectiveTo assess the anti-seizure efficacy and safety of a C10-enriched medium-chain triglyceride (MCT) ketogenic diet (KD) compared with the classic KD in pediatric patients with refractory epilepsy.MethodsThis 16-week, open-label, randomized, controlled, crossover pilot study was conducted at Severance Children’s Hospital, Seoul, South Korea, between August 2022 and September 2023. Fifteen pediatric patients with refractory epilepsy were enrolled and received classic KD and C10-enriched KD for 8 weeks each. The study compared seizure reduction rate, tolerability, and safety of the two diets.ResultsFifteen patients were enrolled. Patients were divided into 2 groups depending on the type of KD initiated. Ten patients completed the trial. Initial treatment with the C10-enriched KD resulted in seizure reduction in all five patients, with two becoming seizure-free. Initial treatment with classic KD was effective in two out of five patients. Upon crossover, those initially on C10-enriched KD maintained their seizure reduction, while patients initially on the classic KD showed additional seizure reduction when switched to C10-enriched KD. Adverse effects included transient hypoglycemia, metabolic acidosis, hypercalciuria, and gastrointestinal symptoms, all of which were manageable.DiscussionThe C10-enriched KD demonstrated comparable efficacy and tolerability to the classic KD, offering a promising option for patients with refractory epilepsy who do not respond adequately to the classic KD alone. This study, the first to directly compare a C10-enriched KD with a classic KD, highlights the potential synergistic effects of decanoic acid.

Efficacy and Blood Levels of Lacosamide in Patients with Focal Epilepsy.

Objectives: The aim of this paper is to analyze clinical targets for lacosamide (LCM) blood levels in patients with focal epilepsy. Referring to the LCM optimal range will encourage us to think about the importance and usefulness of measuring its blood levels. Methods: A total of 101 (45 female, 56 male) patients were treated with LCM. Blood sampling was performed 1 month after the start of oral medication (the levels reached a steady state) if the LCM treatment had been continued, and then 6 and 12 months after. The efficacy of LCM was evaluated by the reduction in the epileptic seizure rate (RR) at the time of blood sampling. The patients were classified as effective cases (seizure reduction rate ≥ 50%) and ineffective cases (<50%). The actual level, the calculated peak/trough levels, and the levels for each type of seizure were investigated. A statistical analysis was performed using Spearman's rank correlation coefficient and the Wilcoxon signed-rank test. Results: A positive correlation was seen between blood levels and dosage (r = 0.446). However, the blood levels and RR showed no correlation. The blood levels were higher in effective cases than in ineffective cases at all time points (measurement p < 0.001, peak p = 0.013, trough p = 0.001). Because the range was set so that the effective and ineffective groups did not overlap, the optimal range of LCM was found to be 8.0-10.5 µg/mL. Conclusions: Measuring and calculating blood levels of LCM and adjusting the dosage to reach the optimal range are recommended. Moreover, the optimal range for LCM was determined as a therapeutic target.

Increased cerebellar vermis volume following repetitive transcranial magnetic stimulation in drug-resistant epilepsy: a voxel-based morphometry study.

Voxel-based morphometry (VBM) was applied to explore structural changes induced by repetitive transcranial magnetic stimulation (rTMS) and the relationship with clinical outcomes. Moreover, the relationship between each segmented regional gray matter (GM) volume was investigated to identify circuits involved in the rTMS treatment process in patients with drug-resistant epilepsy (DRE). Nineteen patients with DRE were finally included in the analysis. A session of rTMS was applied for 5 consecutive days. Participants received either 1,000 or 3,000 pulses, at a frequency of 0.5 Hz and the intensity was set at 90% of the individual's resting motor threshold. VBM analysis was performed to explore regional GM volume changes 2 months after rTMS application. The regional volume change was correlated with seizure reduction rate. Relationships between changes in GM volume in each anatomically parcellated region were analyzed using a fully-automated segmentation pipeline. Compared to the baseline, seizure frequency was reduced, and quality of life was improved after rTMS treatment. Regional volume was increased in the cerebellar vermis 2 months after rTMS application. The increased cerebellar vermis volume correlated with the reduced seizure frequency. Regional volume changes in the cerebellar vermis were correlated with changes in the subcortical and cortical GM regions including the thalamus, caudate, and frontal cortex. These results indicate that rTMS treatment effectively reduced seizure frequency in patients with DRE. Increased volume in the cerebellar vermis and activations of the cerebello-thalamo-cortical circuit may be a crucial mechanism underlying the effectiveness of rTMS application in patients with DRE.

Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and efficacy of perampanel in Chinese pediatric patients with epilepsy

ObjectiveThis study was the first to evaluate the effect of CYP3A4 gene polymorphisms on the plasma concentration and effectiveness of perampanel (PER) in Chinese pediatric patients with epilepsy. MethodsWe enrolled 102 patients for this investigation. The steady-state concentration was determined after patients maintained a consistent PER dosing regimen for at least 21 days. Plasma PER concentrations were measured using liquid chromatography–tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final check-up. ResultsThe CYP3A4×10 GC phenotype exhibited the highest average plasma concentration of PER at 491.1 ± 328.1 ng/mL, in contrast to the CC phenotype at 334.0 ± 161.1 ng/mL. The incidence of adverse events was most prominent in the CYP3A4×1 G TT and CYP3A4×10 GC groups, with rates of 77.8 % (7 of 9 patients) and 50.0 % (46 of 92 patients), respectively. Moreover, the percentage of patients for whom PER was deemed ineffective was least in the CYP3A4×1 G TT and CYP3A4×10 CC groups, recorded at 11.1 % (1 of 9 patients) and 10.0 % (1 of 10 patients), respectively. There was a significant correlation between PER plasma concentration and either exposure or toxicity (both with p < 0.05). We suggest a plasma concentration range of 625–900 ng/mL as a suitable reference for PER in Chinese patients with epilepsy. ConclusionThe CYP3A4×10 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A4 genetic phenotype should be factored in when prescribing PER to patients with epilepsy.

The comparison of DBS and RNS for adult drug-resistant epilepsy: a systematic review and meta-analysis.

Neuromodulation has been proven to be a promising alternative treatment for adult patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) and responsive neurostimulation (RNS) were approved by many countries for the treatment of DRE. However, there is a lack of systematic studies illustrating the differences between them. This meta-analysis is performed to assess the efficacy and clinical characteristics of DBS and RNS in adult patients with DRE. PubMed, Web of Science, and Embase were retrieved to obtain related studies including adult DRE patients who accepted DBS or RNS. The clinical characteristics of these patients were compiled for the following statistical analysis. A total of 55 studies (32 of DBS and 23 of RNS) involving 1,568 adult patients with DRE were included in this meta-analysis. There was no significant difference in seizure reduction and responder rate between DBS and RNS for DRE. The seizure reduction of DBS and RNS were 56% (95% CI 50-62%, p > 0.05) and 61% (95% CI 54-68%, p > 0.05). The responder rate of DBS and RNS were 67% (95% CI 58-76%, p > 0.05) and 71% (95% CI 64-78%, p > 0.05). Different targets of DBS did not show significant effect on seizure reduction (p > 0.05). Patients with DRE who accepted DBS were younger than those of RNS (32.9 years old vs. 37.8 years old, p < 0.01). The mean follow-up time was 47.3 months for DBS and 39.5 months for RNS (p > 0.05). Both DBS and RNS are beneficial and alternative therapies for adult DRE patients who are not eligible to accept resection surgery. Further and larger studies are needed to clarify the characteristics of different targets and provide tailored treatment for patients with DRE.

Efficacy and tolerability of classical and polyunsaturated fatty acids ketogenic diet in controlling paediatric refractory epilepsy – A randomized study

ObjectivesTo measure and compare the efficacy and tolerability of a classical ketogenic diet (CKD) and a polyunsaturated fatty acids ketogenic diet (PUFAKD) in managing childhood refractory epilepsy. Efficacy was assessed by measuring the change in seizure frequency at 3, 6, 9, and 12 months within and between groups. The percentage reduction in seizures at <50 %, 50–90 %, >90 %, and 100 % was also measured. Tolerability was assessed and compared by recording adverse events - vomiting, nausea, lethargy, and constipation. Methods52 children, aged 2–10 years, were randomized, 25 in the CKD group and 27 in the PUFAKD group. Fat: carbohydrate + protein ratio of 2.2:1–4:1 was maintained in both diets; the PUFAKD group only used unsaturated fats with an omega 3: omega 6 ratio of 1:2.8. Ketone levels were measured using keto-dipsticks, with 4+ and 4++ (80–160 mg/dL) being the most optimal values. ResultsA significant decrease (p=0.001) in seizures was observed (n=52), with no significant difference (p=0.537) between the two groups. The mean seizure reduction was 71.1 %, with no significant difference (p=0.488) in both groups. The mean compliance rate was 78.3 % (n=52). A statistically significant linear trend existed between a higher compliance rate and a greater reduction in seizures (p = 0.042, Z=4.039) among all children (n=52). Nausea (p=0.033) and vomiting (p=0.014) occurred more in PUFAKD than in CKD. ConclusionNo significant difference was seen in seizure reduction between the two groups. Compliance correlates with a greater seizure reduction. Despite similar seizure reduction rates, the novel PUFAKD exhibited poorer compliance and more pronounced adverse effects compared to CKD. CKD remained a superior choice over the novel PUFAKD in the management of paediatric refractory epilepsy. More controlled trials with varying PUFA compositions are recommended for long-term evaluations.

Effects of CYP3A5*3 genetic polymorphisms on the pharmacokinetics of perampanel in Chinese pediatric patients with epilepsy.

This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy. We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup. The plasma concentration showed a linear correlation with the daily dose taken ( r = 0.17; P < 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5 ± 297.1 vs. 633.8 ± 305.5 μg/ml; P = 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2 ± 1.7 vs. 3.8 ± 2.0; P = 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8 ± 293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1 ± 165.6 ng/ml and 260.0 ± 36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8 ± 285.6 vs. 433.0 ± 227.2 ng/ml; P = 0.042). The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.

A survey of preferences and expectations for surgical interventions targeting atonic seizures in Lennox-Gastaut syndrome.

To assess preferences and outcome expectations for vagus nerve stimulation (VNS) and corpus callosotomy (CC) surgeries in the treatment of atonic seizure in Lennox-Gastaut syndrome (LGS). A total of 260 surveys were collected from patients are caregivers of LGS patients via Research Electronic Data Capture (REDCap). Respondents reported an average acceptable atonic seizure reduction rate of 55.9% following VNS and 74.7% following CC. 21.3% (n = 50) were willing to be randomized. Respondents reported low willingness for randomization and a higher seizure reduction expectation with CC. Our findings guide surgical approaches for clinicians to consider patient preference in order to design future studies comparing effectiveness between these two procedures.

Seizure Cycles under Pharmacotherapy.

This study was undertaken to determine the effects of antiseizure medications (ASMs) on multidien (multiday) cycles of interictal epileptiform activity (IEA) and seizures and evaluate their potential clinical significance. We retrospectively analyzed up to 10 years of data from 88 of the 256 total adults with pharmacoresistant focal epilepsy who participated in the clinical trials of the RNS System, an intracranial device that keeps records of IEA counts. Following adjunctive ASM trials, we evaluated changes over months in (1) rates of self-reported disabling seizures and (2) multidien IEA cycle strength (spectral power for periodicity between 4 and 40 days). We used a survival analysis and the receiver operating characteristics to assess changes in IEA as a predictor of seizure control. Among 56 (33.3%) of the 168 adjunctive ASM trials suitable for analysis, ASM introduction was followed by an average 50 to 70% decrease in multidien IEA cycle strength and a concomitant 50 to 70% decrease in relative seizure rate for up to 12 months. Individuals with a ≥50% decrease in IEA cycle strength in the first 3 months of an ASM trial had a higher probability of remaining seizure responders (≥50% seizure rate reduction, p < 10-7) or super-responders (≥90%, p < 10-8) over the next 12 months. In this large cohort, a decrease in multidien IEA cycle strength following initiation of an adjunctive ASM correlated with seizure control for up to 12 months, suggesting that fluctuations in IEA mirror "disease activity" in pharmacoresistant focal epilepsy and may have clinical utility as a biomarker to predict treatment response. ANN NEUROL 2024;95:743-753.

Efficacy of Levetiracetam as Add-On Therapy in the Treatment of Seizures in Neonates

Introduction: There is no consensus regarding the efficacy of add-on therapy with levetiracetam (LEV) in the treatment of seizures in neonates. The aim of this study was to evaluate the efficacy of add-on therapy with LEV for achieving >80% seizure reduction after phenobarbital (PB) treatment. Methods: Retrospective cohort study of near term neonates admitted to the neonatal intensive care unit with EEG-confirmed seizures despite treatment with PB as first-line therapy and using LEV as 2nd-, 3rd- or 4th-line treatment. Antiseizure medication was administered according to national guidelines. All neonates were monitored with 2-channel amplitude-integrated electroencephalography. The total seizure burden in minutes, 2 h before and 4 h after administration of LEV, was calculated using raw EEG. Primary outcome was the efficacy of LEV in achieving >80% seizure reduction. The efficacy of additional midazolam (MDZ) and lidocaine (LDC) was also calculated. Results: A total of 47 full-term neonates were included. The mean total loading dose of LEV was 40 mg/kg (36–44 mg/kg). Seizure etiology consisted of hypoxic-ischemic encephalopathy (n = 11), hemorrhagic or ischemic stroke (n = 16), central nervous system infection (n = 8), genetic (n = 8), metabolic disorders (n = 3), and unknown (n = 1). Following LEV administration, >80% seizure reduction was observed in 17% (8/47) of neonates, whereas it was 23% (6/26) after MDZ and 92% (23/25) after LDC administration. Discussion: Although the cumulative loading dose of LEV was low and the group of infants studied was heterogeneous, the efficacy of LEV as add-on therapy for the treatment of seizures in neonates was limited. The highest seizure reduction rate was seen after LDC administration.

Plasma Concentration, Efficacy, and Tolerability of Perampanel in Chinese Pediatric Patients with Epilepsy: Real-World Clinical Experience.

Information on the efficacy and plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy is limited. Therefore, this real-world retrospective study aimed to assess the efficacy, tolerability, and plasma concentration of the maximum dose of PER for epilepsy treatment in Chinese pediatric patients. A total of 107 pediatric patients from 2 hospitals in China were enrolled in this study. The plasma concentration of PER was determined using ultrahigh-performance liquid chromatography. The primary efficacy endpoint was the seizure reduction rate after PER treatment at the last follow-up. The response rate to PER therapy was 59.8% (64/107). The authors observed that patients younger than 6 years of age (n = 49) showed a significantly lower concentration-to-dose ratio than patients with ages between 6 and 14 years (n = 58) (2.2 ± 1.7 vs. 3.0 ± 1.8 mcg·mL -1 ·kg·mg -1 , respectively; P < 0.05). Patients who received enzyme-inducing antiseizure medication had significantly lower concentration-to-dose ratios than those who did not receive enzyme-inducing antiseizure medication (EIASM) (2.1 ± 1.8 vs. 3.1 ± 2.0 mcg·mL -1 ·kg·mg -1 , P < 0.05). A total of 37 patients (34.6%) reported treatment adverse events. Patients with somnolence and irritability had a significantly higher PER plasma concentration than the "no treatment-emergent adverse effect" groups ( P < 0.05). PER is an effective and well-tolerated treatment option for patients with epilepsy. To ensure the clinical efficacy and safety of PER in pediatric patients, it is necessary to monitor its plasma concentrations.

Long-term effectiveness and seizure recurrence risk factors of ketogenic diet for pediatric refractory epilepsy: Experience from a tertiary care center in China.

This study aimed to assess the long-term effectiveness and seizure recurrence risk in children with drug-resistant epilepsy who achieved seizure freedom on a ketogenic diet (KD). Predictors associated with seizure recurrence were also evaluated. Patients with drug-resistant epilepsy who received KD therapy for at least 3 months between May 2011 and April 2020 were included. The clinical efficacy of the KD was evaluated. Patients who achieved seizure freedom for at least 3 months on the KD were focused. Multivariate Cox regression models were used to explore the risk factors of seizure relapse in patients who achieved seizure freedom. This study included 288 patients (163 males, 125 females). The seizure-free rates of the KD at 3, 6, 12, and 24 months were 9.7%, 16.7%, 14.2%, and 9.0%, respectively. Additionally, the seizure reduction rates between 50% and 99% were 46.5%, 39.9%, 30.2%, and 20.5%, respectively. Patients with Angelman syndrome (AS) showed the highest efficacy rate, followed by those with Dravet syndrome (DS). 51 patients achieved at least 3 months of seizure freedom on the KD. Seizures recurred in 24 (47.1%) patients. None of the patients with AS relapsed, while those with DS had the highest recurrence rate. The etiology of epilepsy, KD maintenance treatment period, and electroencephalography (EEG) abnormalities during follow-up differed significantly between patients with and without recurrence. However, multivariate Cox regression analysis indicated that a KD maintenance treatment period of less than 12 months and the presence of EEG abnormalities during follow-up were significantly correlated with a higher risk of relapse. Epilepsy control was restored in 3 of the 24 (12.5%) patients who experienced relapse. KD appears to be effective in children with various types of drug-resistant epilepsy. A short KD maintenance treatment period and EEG abnormalities during follow-up were associated with an increased risk of seizure recurrence.

Feasibility of ketogenic diet therapy variants for refractory epilepsy in neonates to infants under 2 years old

BackgroundKetogenic diet Therapy (KDT) has been reported as a possible beneficial management strategy for controlling seizures in infants aged <2 years, but the safety and efficacy of this therapy remain to be investigated. We investigated the achievability, tolerability, efficacy, and safety of KDT for patients under 2 years old. Materials and methodsInfants younger than 2 years old with pharmacoresistant epilepsy were enrolled in this prospective study. We divided cases into three age groups: I) neonates; II) infants aged 1–12 months; III) infants aged 12–24 months. KDT initiation protocol were administration through parenteral route, enteral route or oral feeding. Seizure reduction rate, physical growth, and adverse effects were assessed at monthly visit. ResultsThirteen patients who completed 6 months of KDT were recruited. There was one neonate in group I, 9 infants in group II, and 3 infants in group III. Eleven of them (11/13, 84.6%) were responders to KDT. All infants with underlying genetic etiology were seizure free after treating with KDT. The starting keto ratio was 1.1 mmol/L in group I, 2.3 mmol/L in group II, and 2.8 mmol/L in group III, which gradually approached 3:1–4:1 over 5–7 days. There were no symptomatic adverse effects or growth retardation in any of the study subjects. ConclusionsKDT is a promising alternative therapy with high feasibility, safety, and efficacy for pharmacoresistant epilepsy in infants under 2 years old, especially for those with genetic etiology. The starting keto ratio should be lower, and the keto ratio titration period should be longer than for children older than 2 years.

Efficacy and Tolerability of Ultra Rapid Duty Cycling Vagus Nerve Stimulation for Medically Refractory Absence Seizures

BackgroundSignificant knowledge gap exists on vagus nerve stimulation (VNS) efficacy and tolerability in medically refractory absence seizures (MRAS). This retrospective review of patients with MRAS aims to narrow this knowledge gap by comparing ultra rapid duty cycling ([URDC] ON time seven seconds, OFF time 0.2 minutes) with less frequent stimulations of rapid duty cycling (RDC, OFF time <1.1 minutes) and normal duty cycling (NDC, OFF time ≥1.1 minutes). MethodsPatients with MRAS aged less than 21 years who underwent VNS implantation were identified. Patient demographics, antiepileptic medications, seizure types, frequency, VNS parameters, outcomes of seizure reduction rate (SRR), and seizure freedom were extracted and compared among NDC, RDC, and URDC patient cohorts. ResultsThirty-six patients with MRAS were identified. After a mean follow-up of 32.6 months, responder rate ([RR], SRR ≥50%) for URDC was 80% for absence seizures and 80% for all seizure types versus 66.67% and 66.77% for NDC and 78.57% and 57.14% for RDC, respectively. Six of 10 patients (60%) on URDC achieved complete seizure freedom. A higher rate of subjective improvement in academic performance, attention, and developmental gain was noted in the URDC group. Patients on URDC tolerated higher output current (mean 3.025 mA) with minimal side effects but required a battery change sooner. ConclusionsVNS is a safe and effective nonpharmacologic management choice in patients with MRAS. The data presented demonstrate that the combination of URDC and high output current provides better RR and seizure freedom. Apart from a reduced battery life, this parameter modality seems to be well-tolerated.

Additional Effect of High-output Current and/or High-duty Cycle in Vagus Nerve Stimulation for Adolescent/Adult Intractable Epilepsy.

A vagus nerve stimulation (VNS) device delivers electrical pulses to the vagus nerve at a rhythm defined by the duty cycle. The standard therapeutic range is advocated for an output current of 1.5-2.25 mA and a duty cycle of 10%. As the optimal settings vary from patient to patient, some patients may benefit from additional seizure reduction when stimulated beyond the standard range. A total of 74 patients (15 children aged <12 years and 59 adolescents/adults) who underwent VNS implantation between 2011 and 2020 and who were followed up for at least 2 years were included in this retrospective study. Stimulation parameters exceeding 2.25 mA of output current, 25% of duty cycle, and 0.5625 (2.25 mA × 25%) of current × duty cycle were defined as high stimulation. The proportion achieved an additional seizure reduction of 20%, and the 50% seizure reduction rate at the last follow-up was compared between adolescents/adults and children. Approximately 40% of patients in adolescents/adults treated with high stimulation experienced an additional acute effect, resulting in a 50% or greater reduction in seizures in almost all patients. Moreover, in adolescents/adults, 22.2%-41.9% of the patients were treated with high stimulation, and the responder rate was 69.5%. Conversely, the responder rate in children was 26.7%, significantly worse than that in adolescents/adults, despite higher stimulation. VNS with high-stimulation settings is effective for adolescent and adult patients with intractable epilepsy. Even high stimulation may not be effective in extremely refractory pediatric epilepsy with a high seizure frequency.

Effects of altered excitation-inhibition imbalance by repetitive transcranial magnetic stimulation for self-limited epilepsy with centrotemporal spikes.

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 (offset and slope) to investigate the improvement of rTMS on the excitation-inhibition imbalance (E-I imbalance) in the brain of this group of children. Eight SeLECTS patients with ESES were included in this study. Low-frequency rTMS (≤1 Hz) 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) were measured to investigate the clinical effects of rTMS. The aperiodic offset and slope were calculated to explore the effect of rTMS on E-I imbalance. 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 3 months 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). 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.

Efficiency of surgery on posttraumatic epilepsy: a systematic review and meta-analysis.

Posttraumatic epilepsy (PTE) accounts for approximately 20% of structural epilepsy, and surgical intervention may be a potential treatment option for these patients. Therefore, the purpose of this meta-analysis is to evaluate the effectiveness of surgical interventions for the management of PTE. Four electronic databases (Pubmed, Embase, Scopus and Cochrane library) were searched to identify studies on surgical management of PTE. Seizures reduction rate were analyzed quantitatively in a meta-analysis. Fourteen studies involving 430 PTE patients were selected for analysis, out of which 12 reported on resective surgery (RS), 2 on vagus nerve stimulation (VNS), and 2 of the 12 RS studies reported that 14 patients underwent VNS. The seizure reduction rate for surgical interventions (both RS and VNS) was 77.1% (95% confidence interval [CI]: 69.8%-83.7%) with moderate heterogeneity (I2 = 58.59%, Phetero = 0.003). Subgroup analysis based on different follow-up times revealed that the seizure reduction rate was 79.4% (95% CI: 69.1%-88.2%) within 5years and 71.9% (95% CI: 64.5%-78.8%) beyond 5years. The seizure reduction rate for RS alone was 79.9% (95% CI: 70.3%-88.2%) with high heterogeneity (I2 = 69.85%, Phetero = 0.001). Subgroup analysis showed that the seizure reduction rate was 77.9% (95% CI: 66%-88.1%) within 5years and 85.6% (95% CI: 62.4%-99.2%) beyond 5years, with 89.9% (95% CI: 79.2%-97.5%) for temporal lobectomy and 84% (95% CI: 68.2%-95.9%) for extratemporal lobectomy. The seizure reduction rate for VNS alone was 54.5% (95% CI: 31.6%-77.4%). Surgical interventions appeared to be effective for PTE patients without severe complications, RS seemed more beneficial than VNS, while temporal lobectomy is more favorable than extratemporal resection. However, further studies with long-term follow-up data are needed to better understand the relationship between VNS and PTE.

Systematic Review and Meta-Analysis of Responsive Neurostimulation in Epilepsy

Neuromodulatory implants provide promising alternatives for patients with drug-resistant epilepsy (DRE) in whom resective or ablative surgery is not an option. Responsive neurostimulation (RNS) operates a unique "closed-loop" system of electrocorticography-triggered stimulation for seizure control. A comprehensive review of the current literature would be valuable to guide clinical decision-making regarding RNS. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols, a systematic PubMed literature review was performed to identify appropriate studies involving patients undergoing RNS for DRE. Full texts of included studies were analyzed and extracted data regarding demographics, seizure reduction rate, responder rate (defined as patients with >50% seizure reduction), and complications were compiled for comprehensive statistical analysis. A total of 313 studies were screened, and 17 studies were included in the final review, representative of 541 patients. Mean seizure reduction rate was 68% (95% confidence interval 61%-76%), and the mean responder rate was 68% (95% confidence interval 60%-75%). Complications occurred in 102 of 541 patients, for a complication rate of 18.9%. A strong publication bias toward greater seizure reduction rate and increased responder rate was demonstrated among included literature. A meta-analysis of recent RNS for DRE literature demonstrates seizure reduction and responder rates comparable with other neuromodulatory implants for epilepsy, demonstrating both the value of this intervention and the need for further research to delineate the optimal patient populations. This analysis also demonstrates a strong publication bias toward positive primary outcomes, highlighting the limitations of current literature. Currently, RNS data are optimistic for the treatment of DRE but should be interpreted cautiously.

A Mixed-Lipid Diet (Medium-Chain and Long-Chain Triglycerides) for Better Tolerability and Efficiency in Pediatric Epilepsy Patients

Purpose: In the past, the use of medium-chain triglycerides (MCTs) for a ketogenic diet (KD) was expected to improve both patients’ and caregivers’ adherence to treatment, but many gastrointestinal problems have been reported. Through a calculated partial administration of MCTs in a KD, we aimed to reduce these complications, while maintaining acceptable seizure reduction. Methods: At a tertiary referral center for pediatric patients with epilepsy, MCT oil was given in a 1:1 ratio with long-chain triglycerides to patients on KDs. Patients who began the diet from February 2019 to February 2020 were reviewed retrospectively, and 47 patients with at least 3 months of follow-up records were enrolled in the studyResults: Overall, 29.8% of patients on a KD with an adjusted MCT ratio experienced complications, such as gastrointestinal symptoms and behavioral food refusal, compared to 63.0% of prior KD patients. The mean seizure reduction rate was 68.45%±40.61%, which was not significantly different from the comparison group’s rate of 64.84%±34.24%. Conclusion: Adjusted MCT incorporation into a KD showed comparable seizure control results, with better tolerability of the diet.

The effectiveness and tolerability of clobazam in the pediatric population: Adjunctive therapy and monotherapy in a large-cohort multicenter study

ObjectiveTo evaluate the effectiveness and tolerability of clobazam therapy in the pediatric population in terms of seizure semiology, epileptic syndromes, and etiological subgroups. MethodsA retrospective cohort study was conducted consisting of 1710 epileptic children from eight centers in seven geographic regions of Turkey. The initial efficacy of clobazam therapy was evaluated after three months of treatment. The long-term effectiveness of the drug, overall seizure outcomes, and overall therapeutic outcomes were evaluated during 12 months of therapy. ResultsAnalysis of initial efficacy after the first three months of clobazam therapy showed that 320 (18.7 %) patients were seizure-free, 683 (39.9 %) had > 50 % seizure reductions, and 297 (17.4 %) had < 50 % seizure reductions. A positive response (seizure-free and >50 % seizure reduction) was determined for focal-onset (62.3 %) seizures, epileptic spasms (61.5 %), and generalized onset seisures (57.4). The highest positive response rate among the epileptıc syndromes was for self-limited epilepsy with centrotemporal spikes (SeLECTS). The highest negative response rate was for developmental and/or epileptic encephalopathies (DEEs). Magnetic resonance imaging (MRI) revealed a structural etiological diagnosis in 25.8 % of the cohort. A higher positive response rate was observed at MRI in patients with sequelae lesions than in those with congenital lesions. The seizure recurrence rate was higher in the patient group with epilepsy wıth genetic and metabolic causes, in individuals with more than one seizure type, and in those using three or more antiseizure drugs. ConclusionsThis cohort study provides additional evidence that clobazam is an effective and well-tolerable drug with a high seizure-free rate (18.7 %), a significant seizure reduction rate (57.3 %), and with excellent overall therapeutic outcomes with a low seizure relapse rate and considerable reversible benefits in the pediatric population.