Reduction In Seizure Frequency Research Articles

The effectiveness and safety of bevacizumab in improving the efficacy of antiseizure medication in treating refractory epilepsy induced by stereotactic radiosurgery in meningiomas

Background: Refractory epilepsy (RE) increases rapidly after stereotactic radiosurgery (SRS), but the reports on RE treatment are rare, with various methods and efficacy. In recent years, bevacizumab (BEV) has been widely used as it is effective in eliminating intracranial oedema and reducing radioactive damage. The aim of this study was to evaluate the application of additional BEV to RE after SRS in the real world. Methods: Seizure freedom and seizure response were defined as 100% and > 50% reduction in seizure frequency at baseline and 6-, 9- and 12-month follow-ups. The sustained seizure-free (SSF), sustained seizure response (SSR) was used to assess the effectiveness of BEV. The number of anti-seizure medications (ASM), seizure severity (NH3), and epilepsy quality of life rating scale (QOLIE-31) scores were compared before and 12 months after treatment. Results: Forty-one patients were included from January 2020 to December 2022. During the 1-year follow-up, 5 patients (12.2%) achieved SSF lasting 12 months, and 4.9% and 7.3% enjoyed SSF more than 6 months and 9 months, respectively. Twelve patients (29.3%) achieved SSR lasting for 12 months, and 19.5% and 24.4% of the study cohort achieved SSR more than 6 months and 9 months, respectively. Patients’ ASM, NH3, and QOLIE-31 scores significantly improved 12 months after treatment, and the adverse reactions were controllable. Conclusion: This study is the first to explore and report the additional use of BEV in the treatment of RE after SRS in meningiomas. BEV was effective and safe in the treatment of SRS-induced RE.

Cenobamate as an Early Adjunctive Treatment in Drug-Resistant Focal-Onset Seizures: An Observational Cohort Study.

Cenobamate (CNB) is a new antiseizure medication (ASM) to treat drug-resistant, focal-onset seizures. Data on its use in early therapy lines are not yet available, and clinicians frequently consider CNB to be a later ASM drug choice. We investigated the efficacy and safety of CNB as an early adjunctive treatment in drug-resistant, focal-onset seizures. The study population were patients with drug-resistant, focal-onset seizures who were initiated with CNB after they did not respond to two or three lifetime ASMs, including all prior and concomitant ASMs. These patients were matched (1:2) by sex, age, and seizure frequency to controls who were initiated with any ASM other than CNB. All participants participated in the Mainz Epilepsy Registry. We evaluated the retention rate after 12 months of CNB and after each new adjunctive ASM in the control group. In addition, seizure freedom and the response rate (reduction of seizure frequency by ≥ 50% from baseline) after 12 months were estimated. We included 231 patients aged 44.4 ± 15.8 years. Of these, 33.3% (n = 77) were on CNB, 19.0% (n = 44) on valproate (VPA), 17.3% (n = 40) on lacosamide (LCS), 16.4% (n = 38) on levetiracetam (LEV), and 13.9% (n = 32) on topiramate (TPM). The highest retention rate after 12 months since the beginning of the early adjunctive therapy was observed on CNB (92.0%), compared with LCS (80.0%), LEV (73.3%), VPA (68.2%), or TPM (62.5%) (p < 0.05). Seizure freedom and response rate were also the best on CNB (19.5% and 71.4%, respectively) compared with other ASMs (8.3% and 52.5%, respectively; p < 0.05). No significant differences in adverse events between CNB and other ASMs were observed. Our study provides evidence that CNB is an effective ASM with a good safety profile in the early therapy lines of drug-resistant, focal-onset seizures. This data should support medical decision making in the management of patients with refractory epilepsy. NCT05267405.

Long-term Effect of Multichannel tDCS Protocol in Patients with Central Cortex Epilepsies Associated with Epilepsia Partialis Continua.

Epilepsia partialis continua (EPC) is a rare type of focal motor status epilepticus that causes continuous muscle jerking in a specific part of the body. Experiencing this type of seizure, along with other seizure types, such as focal motor seizures and focal to bilateral tonic-clonic seizures, can result in a disabling situation. Non-invasive brain stimulation methods like transcranial direct current stimulation (tDCS) show promise in reducing seizure frequency (SF) when medications are ineffective. However, research on tDCS for EPC and related seizures is limited. We evaluated personalized multichannel tDCS in drug-resistant EPC of diverse etiologies for long-term clinical efficacy We report three EPC patients undergoing a long-term protocol of multichannel tDCS. The patients received several cycles (11, 9, and 3) of five consecutive days of stimulation at 2mA for 2 × 20min, targeting the epileptogenic zone (EZ), including the central motor cortex with cathodal electrodes. The primary measurement was SF changes. In three cases, EPC was due to Rasmussen's Encephalitis (case 1), focal cortical dysplasia (case 2), or remained unknown (case 3). tDCS cycles were administered over 6 to 22 months. The outcomes comprised a reduction of at least 75% in seizure frequency for two patients, and in one case, a complete cessation of severe motor seizures. However, tDCS had no substantial impact on the continuous myoclonus characterizing EPC. No serious side effects were reported. Long-term application of tDCS cycles is well tolerated and can lead to a considerable reduction in disabling seizures in patients with various forms of epilepsy with EPC.

Diagnostic and prognostic significance of serum interleukins in epileptic encephalopathy with spike wave activation in sleep (EE-SWAS) syndrome

ObjectiveTo study serum interleukin-6(IL-6), interleukin-8(IL-8) and interleukin-10(IL-10) levels in Epilpetic encephalopathy with spike-wave activation in sleep(EE-SWAS), drug refractory epilepsy(DRE) and well controlled epilepsy(WCE). MethodsChildren(2–12 years) with immunotherapy naïve EE-SWAS, DRE and WCE were enrolled. Valid psychometric tools were used to assess cognition and behavior. Children with EE-SWAS were longitudinally followed. They received a three-month steroid course alongwith the ongoing antiseizure drugs. Electroclinical responders were defined as change in social quotient by 5-points with improvement in atleast one behavioral domain by 5-points and 50 % reduction in mean seizure frequency if active seizures were present alongwith a 25 % reduction in Spike-wave-index(SWI) at three months. Change in serum Interleukin levels at one month follow up was compared between participants who eventually became responders or non-responders at three months. ResultsTwenty children with EE-SWAS, 18 with DRE and WCE each were enrolled. Serum IL-6(pg/ml){(EE-SWAS: 3.775(IQR 2.205, 11.28); DRE: 3.01(IQR 2.04, 4.56); WCE: 1.655(IQR 1.27, 2.29), p = 0.0065} and IL-8(pg/ml){(EE-SWAS: 103.2(IQR 34.01, 200.82); DRE: 19.595(IQR 16.54, 39.7); WCE: 18.97(IQR 16.54, 21.91) p = 0.0002} was significantly different between the three groups. In EE-SWAS group 12/20(60 %) showed electroclinical response to steroids. Responders had significant reduction in IL6 levels (pg/ml){4.045(IQR 2.605, 18.96) to 1.13(IQR 054, 1.74)} at one month follow up compared to non responders {3.12(IQR 1.655, 5.27) to 4.37(IQR 2.83, 9.855)} (p = 0.0069). ConclusionsProinflammatory cytokines (IL-6 and IL-8) are significantly elevated in EE-SWAS compared to DRE and WCE. Reduction in IL-6 levels at one month post-therapy predicted electroclinical responders at 3months follow up.

Deep brain stimulation of hippocampus in treatment of refractory temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common cause of focal onset seizures, affecting 40% of adolescents and adults with epilepsy. TLE is also one of the most common drug resistant forms of epilepsy. Surgical resection remains the treatment of choice for TLE, but not all patients with TLE are suitable candidates for resective neurosurgery. For such patients, deep brain stimulation (DBS) of the hippocampus remains a reversible and efficient treatment alternative. We undertook a systematic review of the literature on hippocampal DBS efficacy and safety in the management of patients with TLE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL), was conducted. We found 14 articles related to hippocampal DBS for the treatment of TLE. The responder rate (defined as at least 50% reduction in seizure frequency) for all patients was 83.4%, Of 99 patients treated by hippocampal DBS, 82 were regarded as responders, and 17 as non-responders. Hippocampal DBS appears to be a safe and efficacious treatment alternative for patients who are not candidates for temporal lobectomy or selective amygdalohippocampectomy due to serious postoperative cognitive deficits. In selected patients with TLE, this neuromodulatory therapy may be very safe and efficacious.

Role of Responsive Neurostimulation in Managing Drug-Resistant Epilepsy: A Systematic Review of Clinical Outcomes.

Drug-resistant epilepsy remains a substantial challenge in neurology, affecting patients who do not respond to conventional antiepileptic drugs. Responsive neurostimulation (RNS) has emerged as a promising therapeutic approach, yet comprehensive reviews synthesizing its clinical outcomes are sparse. This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and involved a comprehensive database search through PubMed, Medline, Embase, the Cochrane Library, and Scopus, covering literature up to April 2024. The review targeted peer-reviewed articles evaluating the efficacy, safety, and quality of life impacts of RNS in patients with drug-resistant epilepsy. Key inclusion criteria encompassed clinical trials, cohort studies, and meta-analyses, while exclusion criteria included non-peer-reviewed and irrelevant studies. We identified five studies meeting our inclusion criteria. These studies collectively demonstrated that RNS significantly reduces seizure frequency and improves quality of life, while maintaining a favorable safety profile. Despite small sample sizes and potential selection biases, the benefits of RNS appeared consistent across diverse patient demographics. RNS represents a viable and effective treatment option for drug-resistant epilepsy, offering significant improvements in seizure control and patient quality of life. Future research should focus on long-term outcomes and refining patient selection to optimize the therapeutic benefits of RNS. The integration of RNS into standard epilepsy management protocols is recommended based on current evidence.

Demonstration of Group-Level and Individual-Level Efficacy Using Time-to-Event Designs for Clinical Trials of Antiseizure Medications.

Participants with treatment-resistant epilepsy who are randomized to add-on placebo and remain in a trial for the typical 3 to 5-month maintenance period may be at increased risk of adverse outcomes. A novel trial design has been suggested, time to prerandomization monthly seizure count (T-PSC), which would limit participants' time on ineffective therapy. We reanalyzed 11 completed trials to determine whether the primary efficacy conclusions at T-PSC matched each of the original, longer trials. A total of 11 double-blind, placebo-controlled trials of levetiracetam, brivaracetam, lacosamide, topiramate, and lamotrigine for either focal-onset or generalized-onset epilepsy were selected. We evaluated the group-level and individual-level efficacy of treatments including the median percent reduction (MPR) in seizure frequency and 50% responder rate (50RR) at T-PSC, time to second seizure, and time to first seizure compared with the full-length trial. The primary efficacy conclusions of 10 of the 11 trials would have been the same with a T-PSC design compared with the traditional design (the exception of lamotrigine had a very high initial placebo response). As a proportion of the full-length effect size, 90% of the MPR and 85% of the 50RR were seen at T-PSC (95% CI 73%-113% and 65%-110%, respectively). Using the T-PSC design, the time on blinded treatment was at least 312 participant-years shorter (40% of total duration) and 142,000 seizures occurred during this time (60% of total seizures). By contrast, the time to first or second seizure designs reproduced group-level effect size, but the primary efficacy conclusions of each trial and individual-level efficacy correspondence were fair to poor. These results support the use of this trial design for new epilepsy medication trials because this reanalysis of 11 randomized controlled trials demonstrated that observation until T-PSC was sufficient to demonstrate efficacy while potentially improving participant safety by reducing the time of exposure to placebo and inadequate treatment. Despite analysis of 11 trials including 3,619 participants, we did not observe a significant reduction in the group-level effect size, which is directly related to statistical power. The next step is to evaluate whether T-PSC is sufficient to evaluate safety as measured by adverse events.

Factors associated with seizure response in adults with epilepsy on a modified Atkins diet

PurposeThis study investigated factors associated with improved seizure control in adults with epilepsy following a modified Atkins diet (MAD). MethodsFollow-up data collected from participants enrolled in a prospective study between March 2016 and November 2023 was analyzed. Demographic and clinical differences between diet responders and non-responders were evaluated. MAD response was defined as ≥ 50 % reduction in seizure frequency from baseline. ResultsMAD use led to clinical response in 48 % of study participants with 2–3 month follow-up and in 56 % of study participants with 6 month follow-up. No significant differences were found for gender, age at diet initiation, age at epilepsy diagnosis, or for number of current or past medications tried. However, a significant relationship emerged between epilepsy type and diet response at 6 months with a response of 100 % seen in adults with generalized epilepsy and a response of only 42 % in adults with focal epilepsy (p = 0.004). Those who responded to the diet showed non-significant increases in many of the measured lipid biomarkers. Levels of apolipoprotein-B and small low-density lipoprotein particles showed significant increases from baseline after 3 months in responders compared to non-responders (p = 0.004 and 0.049, respectively). ConclusionsThese findings support the continued use of MAD particularly for seizure management in adults with generalized epilepsy and highlight potential mechanisms of clinical response involving lipoprotein and energy metabolism.

Seizure burden and healthcare resource utilization among people living with drug-resistant focal epilepsy in the United States

Objective This study investigated clinical characteristics, burden of uncontrolled seizures, and seizure-related healthcare resource utilization (HRU) among individuals living with drug-resistant focal epilepsy (FE) in the United States (US). Methods Medical charts of adults with drug-resistant FE who initiated third-line (3 L) anti-seizure medication were extracted from clinical practices in the US (1/1/2013–1/31/2020). The index date, defined as the date of 3 L initiation, was used to indicate the emergence of drug resistance. Individuals on cenobamate were followed for any length of time from the index date. Demographic and clinical characteristics were analyzed descriptively. Primary clinical outcomes included seizure burden (i.e. change in seizure frequency and time to the first and second seizure events) and epilepsy-related HRU. Results Overall, 189 neurologists/epileptologists contributed 345 charts of individuals living with drug-resistant FE (66% male; average age 24 years at diagnosis and 32 years at index date). 66% had ≥1 neurologic/neuropsychiatric comorbidity at baseline. Average monthly seizure rate decreased from 6.1 at baseline to 3.8 at follow-up; however, nearly half of individuals experienced worse/no change or only some improvement (<50% reduction) in seizure frequency. Most individuals (91%) had ≥1 epilepsy-related outpatient visit during follow-up. Unplanned HRU included emergency department visits (43%) and hospitalizations (24%), primarily due to breakthrough seizure events. Conclusion Despite the availability of many anti-seizure medications in the US, people living with drug-resistant FE continue to experience multiple seizures per month and incur substantial healthcare resources. Novel pharmacotherapies may help individuals living with drug-resistant epilepsy achieve seizure freedom.

Exploring the efficacy and safety of cannabidiol in individuals with epilepsy: an umbrella review of meta-analyses and systematic reviews.

Epilepsy ranks among the most prevalent neurological conditions worldwide. Cannabidiol (CBD) has received authorization for epilepsy treatment, yet utilizing CBD is linked to a variety of adverse events (AEs). This umbrella review aims to explore risk and frequency of AEs in epilepsy patients undergoing treatment with CBD. International electronic databases comprising Scopus, PubMed, and Web of Science were extensively searched from the most ancient data accessible until May 2024. In line with fundamental principle of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA), this umbrella review was executed. RStudio software version 2023.03.1 along with R software 4.3.2 was used for our statistical analyses. Thirteen meta-analyses and systematic reviews were included. CBD use in epileptic patients compared to controls can be meaningfully linked with 10.87% becoming seizure-free (RD: 10.87%, 95%CI: 2.39%, 19.34%; I2 = 80%). Compared to controls, a meaningful 73% increase in 50% or greater reduction in seizure frequency was observed (RR: 1.73, 95%CI: 1.47, 2.03; I2 = 0%). In epileptic individuals who using CBD with the dosage of 20mg/kg/d, a higher incidence of treatment withdrawal was detected (RR: 4.39, 95%CI: 2.46, 7.83; I2 = 0%). In this umbrella review of meta-analyses and systematic reviews, CBD use in epileptic patients was linked to an increased risk of ample AEs. Further research, specifically targeting various epilepsy categories, is essential to fully understand the effectiveness and potential side effects of CBD across different epilepsy forms.

The positive Mozart effect on people with epilepsy: Is there some truth in this claim?

The positive treatment effect of Mozart's melody on patients with epilepsy, which was propagated in the late 1990s, was investigated in 29 papers. Commonly, the first movement of the sonata for two pianos KV 448 was played with many repetitions. At least a fifth of the patients achieved a reduction of seizure frequency of more than 50%. Patients with epileptic discharges from the occipital lobe responded very rarely. The mechanism of the effect is not clear, but the melodic aspects seem to have a significant role in this context.

Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program.

This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy. This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (≥50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses. A total of 236 subjects with a median age of 38 (Q1-Q3 = 27-49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q1-Q3 = 2.50-4.47) at baseline to 2.50 (Q1-Q3 = 1.67-3.50) at 12 months (p < .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and γ-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel. Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam.

Combination of or Transition between Deep Brain Stimulation and Responsive Neurostimulation for the Treatment of Drug-Resistant Epilepsy

Introduction: Neuromodulation is an important treatment modality for patients with drug-resistant epilepsy who are not candidates for resective or ablative procedures. However, randomized controlled trials and real-world studies reveal that a subset of patients will experience minimal reduction or even an increase in seizure frequency after neuromodulation. We describe our experience with patients who undergo a second intracranial neuromodulation procedure after unsatisfactory initial response to intracranial neuromodulation. Methods: We performed a retrospective chart review to identify all patients who had undergone deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) or responsive neurostimulation (RNS), followed by additional intracranial neuromodulatory procedures, with at least 12 months of follow-up. Demographic and clinical data, including seizure frequencies, were collected. Results: All patients had temporal lobe epilepsy. Six patients were treated with concurrent ANT DBS and temporal lobe RNS, and 3 patients transitioned between neuromodulation systems. Of the patients treated concurrently with ANT DBS and temporal lobe RNS, 5 of the 6 patients experienced additional reduction in seizure frequency after adding a second neuromodulation system. Of the patients who switched between neuromodulation modalities, all patients experienced further reduction in seizure frequency. Conclusions: For patients who do not experience adequate benefit from initial therapy with ANT DBS or temporal lobe RNS, the addition of a neuromodulation system or switching to a different form of neuromodulation may allow for additional reduction in seizure frequency. Larger studies will need to be performed to understand whether the use of multiple systems concurrently leads to improved clinical results in patients who are initially treatment resistant to neuromodulation.

Fenfluramine treatment in pediatric patients with Dravet syndrome reduces seizure burden and overall healthcare costs: A retrospective and observational real-world study.

Dravet syndrome is a developmental and epileptic encephalopathy characterized by early onset epilepsy with multiple seizure types often intractable to treatment. Randomized clinical trials have demonstrated how treatment with fenfluramine significantly reduces seizure frequency in patients with Dravet syndrome. The study aims to (1) describe the efficacy and tolerability of fenfluramine in a Danish cohort of patients with Dravet syndrome; and (2) evaluate whether treatment with fenfluramine reduces epilepsy-related hospital contacts administrated by pediatricians or epilepsy-trained nurses. A retrospective registry-based cohort study at the Danish Epilepsy Centre, Filadelfia, Dianalund, Denmark, enrolled 30 pediatric patients with Dravet syndrome treated with fenfluramine between 2017 and 2023. Thirty patients with Dravet syndrome (aged 3-21 years, 12 females) with a verified pathogenic SCN1A variant were included. They were treated with fenfluramine at a mean duration of 29 months with a mean maintenance dose of 0.5 mg/kg/day. The number of patient-years on treatment was 75 years. At last follow-up, 6 patients had discontinued treatment due to lack of efficacy or adverse effects. In the remaining 24 patients, generalized tonic-clonic seizures were reduced by ≥30% in 83%, by ≥50% in 67%, and by 100% in 25%. Additionally, 71% of the patients were reduced in concomitant anti-seizure medication, and 75% experienced a reduction (mean reduction at 52%, range 11%-94%) in epilepsy-related hospital contacts from baseline to the end of the treatment period. Treatment with fenfluramine effectively reduced seizure frequency and concomitant antiseizure medication in patients with Dravet syndrome. Furthermore, a decrease in epilepsy-related contacts by 80% was observed over 6 years of treatment, which may indicate cost-effective benefits. Patients with Dravet syndrome suffer from severe epileptic seizures that are difficult to treat with medication. Earlier, treatment with fenfluramine (an anti-seizure medication) has been documented to decrease the total number of seizures in patients with Dravet syndrome. This publication summarizes the experiences with fenfluramine in children with Dravet syndrome at the Danish Epilepsy Centre, Filadelfia, Dianalund, Denmark. Our publication also illustrates that treatment with fenfluramine may reduce the patients' number of yearly contacts with doctors and nurses specialized in epilepsy treatment, which may indicate cost-effectiveness.

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.

Cannabinoid receptor 2 agonist AM1241 alleviates epileptic seizures and epilepsy-associated depression via inhibiting neuroinflammation in a pilocarpine-induced chronic epilepsy mouse model

Increasing evidence suggests that cannabinoid receptor 2 (CB2R) serves as a promising anti-inflammatory target. While inflammation is known to play crucial roles in the pathogenesis of epilepsy, the involvement of CB2R in epilepsy remains unclear. This study aimed to investigate the effects of a CB2R agonist, AM1241, on epileptic seizures and depressive-like behaviors in a mouse model of chronic epilepsy induced by pilocarpine. A chronic epilepsy mouse model was established by intraperitoneal administration of pilocarpine. The endogenous cannabinoid system (eCBs) in the hippocampus was examined after status epilepticus (SE). Animals were then treated with AM1241 and compared with a vehicle-treated control group. Additionally, the role of the AMPK/NLRP3 signaling pathway was explored using the selective AMPK inhibitor dorsomorphin. Following SE, CB2R expression increased significantly in hippocampal microglia. Administration of AM1241 significantly reduced seizure frequency, immobility time in the tail suspension test, and neuronal loss in the hippocampus. In addition, AM1241 treatment attenuated microglial activation, inhibited pro-inflammatory polarization of microglia, and suppressed NLRP3 inflammasome activation in the hippocampus after SE. Further, the therapeutic effects of AM1241 were abolished by the AMPK inhibitor dorsomorphin. Our findings suggest that CB2R agonist AM1241 may alleviate epileptic seizures and its associated depression by inhibiting neuroinflammation through the AMPK/NLRP3 signaling pathway. These results provide insight into a novel therapeutic approach for epilepsy.

Outcomes of surgical resection and vagus nerve stimulation in patients with medically refractory epilepsy and glutamic acid decarboxylase 65 antibody positivity.

Epilepsy associated with high-titer glutamic acid decarboxylase 65 (GAD65) IgG is often refractory to immunotherapies and antiseizure medication. This study sought to determine the efficacy of vagus nerve stimulation (VNS) and surgical resection in patients with drug-resistant epilepsy associated with GAD65-IgG. We retrospectively identified 15 patients with drug-resistant epilepsy and high serum GAD65 antibody titers (>20 nmol·L-1) who underwent VNS implantation (n = 6), surgical resection (n = 7), or both (n = 2). A responder to VNS was defined as someone with a ≥50% reduction in seizure frequency, and a favorable surgical outcome was defined as Engel I-II. Of the eight patients who underwent VNS implantation, three (37.5%) were initially responders, but this was not sustained in two. Of the nine patients who underwent surgical resection, three (33.3%) had a favorable outcome; however, only one patient was seizure-free at last follow-up. Pathology was available in six patients, and only one had evidence of inflammation; this patient had seizure onset 1 year prior to surgery. Favorable seizure outcome correlated with older age at time of resective surgery, with a trend favoring later age of seizure onset. Taken together, surgical resection and VNS implantation may have limited efficacy in this patient population but can be considered in carefully selected cases.

Analysis of the use of vagus nerve stimulator in the treatment of epilepsy

Refractory epilepsy poses a significant challenge in neurology due to approximately 30% of patients being resistant to conventional pharmacological treatments. This study investigates the efficacy and safety of vagus nerve stimulation (VNS) as a therapeutic alternative for these patients. The primary objective is to analyze the reduction in seizure frequency and improvements in the quality of life of patients treated with VNS. Additionally, the study aims to identify and categorize the side effects associated with the use of VNS. The methodology adopted included a qualitative bibliographic review covering renowned databases such as Scielo, Google Scholar, specialized scientific journals, academic repositories, and virtual libraries. Inclusion criteria considered studies that directly addressed the use of VNS in the treatment of epilepsy, while exclusion criteria eliminated duplicate and methodologically inadequate publications. Results indicate that VNS is effective in reducing seizures and improving quality of life, despite potential side effects. It is concluded that VNS is a viable and cost-effective therapeutic option for patients with refractory epilepsy, highlighting the need for future research to optimize stimulation parameters and minimize adverse effects.

Re-PROGRAM: The evaluation of a brief intervention program for patients with functional seizures in an outpatient hospital setting.

Functional seizures (FS) account for 20%-25% of referrals to specialist epilepsy clinics. They are associated with major disability, increased mortality, and frequent and costly health care use. Current guidelines emphasize the importance of implementing clinical pathways to coordinate and deliver effective treatment, but there are few targeted evidence-based interventions that reliably improve patient outcomes, and treatment resources are limited. We conducted a retrospective evaluation of Re-PROGRAM, a novel, brief intervention for functional seizure patients, to assess its feasibility in an outpatient setting. Twenty-nine patients with FS undertook Re-PROGRAM between August 2020 and January 2022 at the Alfred Hospital Functional Seizures Clinic, Melbourne, Australia. The intervention comprised five 60-90-min consecutive weekly appointments via telehealth, where psychologists engaged patients in a structured program of seizure management skills, lifestyle modification, and behavioral activation strategies. Following the intervention, patient feedback was collected in routine clinical follow-up as well as with a 24-item self-report pre-/postintervention comparison questionnaire. All 29 patients who enrolled in Re-PROGRAM completed the scheduled sessions. Of those who returned the postintervention questionnaire (n = 16), 15 reported a reduction in seizure frequency. Four patients were lost to follow-up. Of the remaining nine, eight reported seizure frequency reduction during clinical follow-up. Qualitative analysis of the feedback revealed the majority of patients reported reduced seizure duration, intensity, and bothersomeness, and patients felt improvements in their sense of control over seizures, confidence to use seizure control strategies, assertive communication, problem solving, coping skills, relationships with others, and their day-to-day functioning. This retrospective evaluation demonstrates the feasibility and acceptability of Re-PROGRAM as a brief intervention for individuals diagnosed with FS delivered in a clinical outpatient setting and warrants further investigation in larger scale, randomized controlled studies.

Cenobamate add-on therapy for drug-resistant focal epilepsy.

Although most people with epilepsy achieve complete seizure cessation, approximately one-third of those with the condition continue experiencing seizures despite the use of antiseizure medications (ASMs) given as monotherapy or polytherapy. In this review, we summarised the evidence from randomised controlled trials (RCTs) about cenobamate as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant ASMs. To assess the efficacy and tolerability of add-on oral cenobamate for the treatment of drug-resistant focal-onset seizures, defined as seizures persisting despite treatment with one or more ASMs. We searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2022). In addition, we contacted the manufacturer of cenobamate and experts in the field to enquire after any ongoing or unpublished studies. RCTs comparing add-on cenobamate to placebo or another ASM in people with focal epilepsy uncontrolled by one or more concomitant ASMs. Two review authors independently selected trials for inclusion, extracted data, performed risk of bias assessment, and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were at least a 50% reduction in total seizure frequency, seizure freedom, and the occurrence of adverse events. We used an intention-to-treat approach for our primary analyses. For each outcome we estimated summary risk ratios (RRs) with their 95% confidence intervals (CIs). We summarised the estimates of effects and certainty of the evidence for each outcome in a summary of findings table. We included two studies (659 adult participants, 442 allocated to cenobamate and 217 to placebo). The overall RR for at least a 50% reduction in seizure frequency for add-on cenobamate at any dose compared to placebo was 2.17 (52% versus 24%, 95% CI 1.66 to 2.84; 2 studies, 605 participants; moderate-certainty evidence). The RR for seizure freedom for add-on cenobamate at any dose compared to placebo was 4.45 (16% versus 5%, 95% CI 2.25 to 8.78; 2 studies, 605 participants; moderate-certainty evidence). The RR for the occurrence of adverse events for add-on cenobamate at any dose compared to placebo was 1.14 (77% versus 67%, 95% CI 1.02 to 1.27; 2 studies, 659 participants; moderate-certainty evidence). We judged the two included RCTs as at low or unclear risk of bias. Both studies were sponsored by the drug company that produces cenobamate. Add-on cenobamate is probably better than placebo in reducing the frequency of seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy uncontrolled by one or more concomitant ASMs (moderate level of certainty). Its use is probably associated with an increased risk of adverse events (moderate level of certainty). Further prospective, controlled trials are required to evaluate the efficacy and tolerability of add-on cenobamate compared to other ASMs. The efficacy and tolerability of cenobamate as adjunctive treatment for focal epilepsy in children should be further investigated. Finally, the long-term efficacy and tolerability of add-on cenobamate treatment in people with other epilepsy types (e.g. generalised epilepsy) or specific epilepsy syndromes, as well as its use as monotherapy, require additional study.