Drug-resistant Epilepsy Research Articles

Effects of vagal nerve stimulation parameters on heart rate variability in epilepsy patients.

Vagal nerve stimulation (VNS) is used as an alternative treatment in drug-resistant epilepsy patients. Effects of VNS on the cardiac autonomic system are controversial. In this study, we aimed to investigate the relationship between VNS parameters and heart rate variability (HRV) in epilepsy patients who underwent VNS treatment. Our study included 31 patients who underwent VNS for drug-resistant epilepsy. Patients were divided into groups according to response to VNS and VNS parameters. All patients underwent 24-h Holter ECG. The mean age of 31 VNS-treated epilepsy patients included in the study was 33.87 ± 7.6 years. When patients were grouped according to VNS response, 25 patients were in the VNS responder group and six patients were in the VNS-nonresponder group. When comparing Holter parameters in the VNS responder and non-responder groups, the median HF was significantly lower in the VNS responder group. VNS duration and signal frequency had a positive effect on LF/HF, while output and off time had a negative effect on LF/HF. When ROC analysis was performed to determine the cut-off values of the parameters for the VNS-responsive state, the AUC value of the HF parameter was 0.780, which was statistically significant. The cut-off value to distinguish response to VNS was 156.9. In conclusion, the effects of VNS parameters on HRV parameters are quite complex. However, the conclusion is that VNS is a neuromodulation method that affects the autonomic system in a complex way. Different levels of VNS parameters may also contribute to this effect. Furthermore, HRV parameters can be used as biomarkers to predict the patient population that may benefit from VNS.

Drug-resistant epilepsy cases in chromosomal pathology

Two cases of epilepsy in patients with a rare hereditary pathology associated with a chromosomal mutation caused deletion of chromosome 14 are presented. In the first case, this pathology was manifested in the child by generalized tonic-clonic seizures, delayed psycho-verbal development, and facial skull microanomaly. In the second case, it was expressed in tonic epileptic seizures, delayed psycho-verbal development, developmental microanomalies, pyramidal atactic syndrome and hand joint hypermobility. Such clinical observations are of professional and scientific interest, as they relate to a rare neurological pathology, with drug-resistant epilepsy as a leading sign.

TRANscranial direct current stimulation for FOcal Refractory epilepsy in mitochondrial disease (TRANSFORM): delayed-start, randomised, double-blinded, placebo-controlled study

BackgroundFocal epilepsy is common in children and adults with mitochondrial disease. Seizures are often refractory to pharmacological treatment and, in this patient group, frequently evolve to refractory focal status epilepticus (also known as epilepsia partialis continua). Where this occurs, the long-term prognosis is poor. Transcranial DC stimulation (tDCS) is a promising, non-invasive, adjunctive treatment alternative to common surgical procedures. Limited recruitment of study participants with this rare disease and the ethical challenges of administering a treatment to one group and not another, while maintaining strict methodological rigour can pose challenges to the design of a clinical study.MethodWe designed the first delayed start, double-blinded, sham-controlled study to evaluate the efficacy of tDCS as an adjunctive treatment for focal epilepsy. We will include participants with a genetically confirmed diagnosis of mitochondrial disease with drug-resistant focal epilepsy aged ≥ 2 years, aiming to collect 30 episodes of focal status epilepticus, each treated for a maximum period of 14 days. The early start intervention arm will receive tDCS from day 1. The delayed start intervention arm will receive sham stimulation until crossover on day 3. Our primary endpoint is a greater than 50% reduction from baseline (on day 0) in seizure frequency assessed by 3x daily reporting, accelerometery, and video monitoring. Changes in the underlying epileptogenic focus within the brain related to the tDCS intervention will be assessed by magnetic resonance imaging (MRI) and/or electroencephalography (EEG).DiscussionStudy results in favour of treatment efficacy would support development of tDCS into a mainstream treatment option for focal epileptic seizures related to mitochondrial disease.Trials registrationISRCTN: 18,241,112; registered on 16/11/2021.

Results of surgical treatment for drug-resistant temporal epilepsy and related predictors of negative post-surgery outcome

Objective: to evaluate the results of surgical treatment and identify related predictors of unfavorable outcome in patients with temporal drug-resistant epilepsy (DRE) in long-term postoperative period.Material and methods. Fifty-one patients with temporal lobe DRE were examined using clinical, neuroimaging, electro- physiological, and laboratory research methods from June 2020 to June 2023. Anteromedial temporal lobectomy (AMLE) and selective amygdalohippocampectomy (SAHE) were performed in 38 (74.5%) and 13 (25.5%) cases, respectively. Postsurgery outcomes were evaluated in 51 patients 6 months later, continued in 43 and 20 patients 1 year and 2 years, respectively, afterwards.Results. The percentage of patients with significant improvement (Engel I/II) 6 months, 1 year and 2 years post-surgery was 82.4%, 72.1%, and 55.0%, respectively. After AMLE vs. SAHE, patients had a more favorable outcome while assessing seizure control. The predictors of unfavorable post-surgery outcome included a prolonged epilepsy course before surgery, the presence of electroencephalography-verified epileptiform activity in postoperative period, and repeated surgical intervention. Patient age, the presence of focal seizures evolving into bilateral tonic-clonic seizures as well as more frequent seizures before surgery were considered as potential predictors.Conclusion. The study results show that quite high effectiveness of seizure control in postoperative period in temporal DRE is quite high that may be accounted for by probability of removing epileptogenic foci and suppression of the mechanisms ensuring emergence and irritation of epileptic discharges. Nevertheless, effectiveness of surgical treatment fades off with time, which requires to further investigate the negative factors countering long-term post-surgery effect. In connection with this, a special attention should be paid to factors such as the presence of electroencephalography-verified epileptiform activity in postoperative period, repeated surgical intervention as well as prolonged epilepsy before surgery.

Recent Advances in Pharmacologic Treatments of Drug-Resistant Epilepsy: Breakthrough in Sight.

Epilepsy affects approximately 1% of the world population. Patients have recurrent seizures, increased physical and psychiatric comorbidities, and higher mortality rate than the general population. Over the last 40 years, research has resulted in 20 new antiseizure medications (ASMs) approved between 1990 and 2018. In spite of this, up to one-third of patients (~ 1 million patients in the USA) have drug-resistant epilepsy (DRE), with little change between 1982 and 2018, a period of intense new ASM development. A minority of patients with DRE may benefit from surgical treatment, but this specialized care remains challenging to scale. Therefore, the greatest hope for breakthroughs for patients with DRE is in pharmacologic therapies.Recently, several advances promise to change the outcomes for patients with DRE. Cenobamate, a drug with dual mechanisms of modulating sodium channel currents and GABA-A receptors, achieves 90-100% seizure reduction in 25-33% of patients with focal DRE, a response not observed with other ASMs. Fenfluramine, a serotonin-acting drug, dramatically reduces the frequency ofconvulsive seizuresin Dravet syndrome, a devastating developmental epileptic encephalopathy with severe DRE.Both drugs reduce mortality.In addition, the possibility of DRE prevention was recently raised in patients with tuberous sclerosis complex, a relatively common genetic form of epilepsy. A paradigm shift is emerging in the treatment of epilepsy. Seizure freedom has become attainable in a significant proportion of patients with focal DRE, and dramatic seizure reduction has been achieved in a developmental encephalopathy. Coupled with a rich pipeline of new compounds under clinical development, the long sought-after breakthrough in the treatment of epilepsy may finally be in sight.

Hippocampal microscopic fractional anisotropy is reduced in temporal lobe epilepsy

Abstract Surgical resection is the method of choice for treating drug-resistant focal temporal lobe epilepsy (TLE). Postsurgical outcomes are better when magnetic resonance imaging (MRI) findings can localize the seizure focus for resection. However, many patients are MR-negative, meaning the focus cannot be differentiated from normal tissue in relaxation-weighted MRI. Diffusion MRI shows promise as a preoperative marker of neuronal abnormalities due to its sensitivity to cellular changes such as axon damage, indexed by fractional anisotropy. Microscopic fractional anisotropy is a recently introduced diffusion MRI metric that is sensitive to axon integrity regardless of axon orientation in both grey and white matter. In contrast, regular fractional anisotropy is only sensitive to axon integrity in coherently oriented bundles of fibers. This work investigated whether microscopic fractional anisotropy is sensitive to hippocampal abnormalities in drug-resistant TLE. Diffusion MRI was performed on a 3T scanner in 19 patients (age = 31±10 years) with drug-resistant TLE (of which 10 were MR-negative) and 18 healthy volunteers (age = 38±15). A deep-learning method was employed to segment the hippocampus into smaller subregions corresponding to the subiculum, cornu ammonis (CA) 1, CA2/3, and CA4 plus dentate gyrus (DG). Mean measurements of subregion volume, diffusivity, fractional anisotropy, and microscopic fractional anisotropy were compared between cohorts. In a subset of the TLE cohort suspected to have unilateral pathology (n=15, age = 32±10 years), the percentage differences between measurements ipsilateral and contralateral to the epileptogenic zone were evaluated to assess asymmetry. Microscopic fractional anisotropy was reduced in the hippocampus of drug-resistant TLE patients relative to healthy volunteers. In subregion-specific analysis, microscopic fractional anisotropy was significantly reduced in only the CA4/DG region in patients compared to healthy volunteers, after corrections for multiple comparisons. In the 15 patients with suspected unilateral pathology, microscopic fractional anisotropy was reliably and statistically lower in the ipsilateral CA4/DG region compared to the contralateral side. Significant differences were not observed between TLE patients and healthy volunteers, or between hemispheres for patients with suspected unilateral pathology, for the fractional anisotropy or volume metrics. Diffusion MRI may complement standard imaging procedures by detecting abnormalities in MRI-negative patients. Due to its ability to detect abnormality regardless of axon orientation, microscopic fractional anisotropy may improve seizure focus localization in surgical candidates.

Low-frequency stimulation of corpus callosum suppresses epileptiform activity in the cortex through γ-aminobutyric acid type B receptor and slow afterhyperpolarization-mediated reduction in tissue excitability.

Deep brain stimulation, particularly low-frequency stimulation (LFS) targeting fiber tracts, has emerged as a potential therapy for drug-resistant epilepsy (DRE) and for generalized epilepsy, both of which pose significant treatment challenges. LFS diffusely suppresses seizures in the cortex when applied to fiber tracts like the corpus callosum (CC). Nevertheless, the specific processes responsible for suppressing epileptic activity in the cortex induced by LFS remain unclear. This study investigates the mechanisms underlying the antiepileptic effect in the cortex of LFS of the CC in coronal rodent brain slices. An invitro 4-aminopyridine (4-AP) seizure model of cortical seizures was generated. LFS stimulation parameters were optimized to provide the largest antiepileptic effect in the cortex when applied to the CC. Changes to tissue excitability and percent time spent seizing were measured due to LFS in artificial cerebrospinal fluid, 4-AP, and in the presence of various specific and nonspecific γ-aminobutyric acid type B (GABAB) and slow afterhyperpolarization (sAHP) antagonists. LFS significantly suppressed seizure activity in the cortex, with an optimal frequency of 5 Hz (76.5%). Tissue excitability during LFS reduces across a wide range of interstimulus intervals, with a maximum reduction at 200 ms. Notably, the tissue excitability remains depressed at 1000 ms. LFS, in the presence of GABAB antagonists, had diminished seizure reduction (<15%) and failed to reduce tissue excitability in the 50-400-ms range. Tissue excitability measured with paired pulses in the 600-1000-ms range was depressed in the presence of GABAB antagonists, suggesting a different antiepileptic mechanism was active. Upon administering sAHP antagonists, seizure reduction was once again diminished (<15%). Upon administration of both sAHP and GABAB antagonists, LFS failed to provide any meaningful seizure reduction (<5%). LFS of the CC provides an antiepileptic effect in the cortex with well-understood mechanisms and could be an alternative to surgical intervention for patients suffering from DRE.

The Emerging Role of Immunoglobulins and Complement in the Stimulation of Neuronal Activity and Repair: Not as Simple as We Thought

Neurologic disorders such as traumatic brain injury, multiple sclerosis, Alzheimer’s disease, and drug-resistant epilepsy have a high socioeconomic impact around the world. Current therapies for these disorders are often not effective. This creates a demand for the development of new therapeutic approaches to treat these disorders. Recent data suggest that autoreactive naturally occurring immunoglobulins produced by subsets of B cells, called B1 B cells, combined with complement, are actively involved in the processes of restoration of neuronal functions during pathological conditions and remyelination. The focus of this review is to discuss the possibility of creating specific therapeutic antibodies that can activate and fix complement to enhance neuronal survival and promote central nervous system repair after injuries associated with many types of neurodegenerative diseases.

Lesion and lesion network localization of dysnomia after epilepsy surgery.

Temporal lobe (TL) epilepsy surgery is an effective treatment option for patients with drug-resistant epilepsy. However, neurosurgery poses a risk for cognitive deficits - up to one third of patients have a decline in naming ability following TL surgery. In this study, we aimed to better understand the neural correlates associated with reduced naming performance after TL surgery, with the goal of informing surgical planning strategies to mitigate the risk of dysnomia. We retrospectively identified 85 patients who underwent temporal lobe (TL) resective surgery (49 left TL, 36 right TL) for whom naming ability was assessed before and >3 months post-surgery using the Boston Naming Test (BNT). We used multivariate lesion-symptom mapping to identify resection sites associated with naming decline, and we used lesion-network mapping to evaluate the broader functional and structural connectivity profiles of resection sites associated with naming decline. We validated our findings in an independent cohort of 59 individuals with left temporal lobectomy, along with repeating all analyses after combining the cohorts. Lesion laterality and location were important predictors of post-surgical naming performance. Naming performance significantly improved after right temporal lobectomy (P = 0.015) while a decrement in performance was observed following left temporal lobectomy (P = 0.002). Declines in naming performance were associated with surgical resection of the left anterior middle temporal gyrus (Brodmann area 21, r =0.41, P = <.001), along with a previously implicated basal temporal language area. Resection sites linked to naming decline showed a functional connectivity profile featuring a left-lateralized network closely resembling the extended semantic \ default mode network, and a structural connectivity profile featuring major temporo-frontal association white matter tracts coursing through the temporal stem. This extends prior work by implicating the left anterior middle temporal gyrus in naming decline and provides additional support for the role of the previously identified basal temporal language area in naming decline. Importantly, the structural and functional connectivity profiles of these regions suggest they are key nodes of a broader extended semantic network. Together these regional and network findings may help in surgical planning and discussions of prognosis.

The effect of synbiotics in the treatment of drug-resistant epilepsy and the parental burden of caregivers: a single-arm pretest-posttest trial

BackgroundIn patients with drug-resistant epilepsy (DRE), the composition of the gut microbiome changes compared to drug-sensitive patients and healthy individuals. Synbiotics, a mixture of probiotics and prebiotics, aim to improve the balance of bacteria in the gut microbiome. This study aimed to assess the effect of synbiotics on the treatment of DRE and the burden on caregivers.MethodsThis one-group pretest-posttest quasi-experimental study was conducted in Arak, Iran. Thirty children with DRE, diagnosed by a pediatric neurologist and meeting the inclusion criteria in 2021-22, were included in the study. In addition to anticonvulsant drugs, infants were administered PediLact at a dose of 5–15 drops per day for eight weeks, and KidiLact at a dose of one sachet per day for eight weeks for children aged 2–15 years. Both PediLact and KidiLact are synbiotics. To investigate the burden on caregivers (parents), the Zarit Caregiver Burden Interview was conducted. In addition, the number of epileptic seizures was assessed from mothers before and immediately after the intervention over one month.ResultsThe mean age of the participants in the study was 8.6 years (SD: 3.4). Eighteen participants (60%) were boys, and 12 (40%) were girls. The results of the study showed a statistically significant decrease in the mean burden on caregivers, from 34.20 (SD: 14.4) before the intervention to 30.26 (SD: 15.8) after the intervention (P = 0.017). The mean frequency of seizures decreased significantly, from 15.83 (SD: 12.9) before the intervention to 12.73 (SD: 12.8) after the intervention (P = 0.001). Following the intervention, the seizure frequency stopped in two patients, decreased by 50% in six patients, increased in one patient, and remained unchanged in 21 patients.ConclusionThe results suggest that Symbiotics in DRE patients are associated with a lower parental burden of caregivers and seizure frequency. Well-designed randomized clinical trial studies are recommended to generate rigorous causal evidence and conclusions.

Empagliflozin modulates seizure activity and oxidative stress in rats with epilepsy

Drug-resistant epilepsy, a commonly devastating condition, affects more than 50 million people globally. Type 2 diabetes mellitus (T2DM) is associated with an increased risk of neurological disorders, and a potential association between epilepsy and subsequent T2DM has emerged. Inhibiting sodium-glucose linked transporters (SGLTs), which are differentially expressed in the brain, has been shown to reduce epileptic episode activity. This study aimed to evaluate the anticonvulsive effect of empagliflozin in rats with seizures induced by maximal electric shock (MES) and pentylenetetrazol (PTZ). Generalized tonic‒clonic seizures were induced in the rats using an electroconvulsive meter, and pentylenetetrazol was injected to induce absence seizures. The duration of all the stages of seizure and Racine stage scoring (RSS) were performed. Malondialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) levels in the brain tissues were determined. Histopathological analysis of the brain tissues was carried out. A significant (p &amp;lt;0.01) decrease in the duration of tonic hind limb extension (THLE), a significant decrease in the levels of pro-oxidants such as MDA and NO, and an increase in the levels of antioxidants such as GSH were observed in the low dose 10 mg/kg and high dose 20 mg/kg empagliflozin groups compared to the disease control group. Histopathological analysis revealed a greater number of healthy neurons with few dark-stained cells in the treatment groups, suggesting the neuroprotective effect of empagliflozin. The present study showed that empagliflozin modulates epileptic activity. Empagliflozin has a potential role in the management of epilepsy in diabetic patients.

Enhancing non-invasive pre-surgical evaluation through functional connectivity and graph theory in drug-resistant focal epilepsy

BackgroundEpilepsy, characterized as a network disorder, involves widely distributed areas following seizure propagation from a limited onset zone. Accurate delineation of the epileptogenic zone (EZ) is crucial for successful surgery in drug-resistant focal epilepsy. While visual analysis of scalp electroencephalogram (EEG) primarily elucidates seizure spreading patterns, we employed brain connectivity techniques and graph theory principles during the pre-ictal to ictal transition to define the epileptogenic network. MethodCortical sources were reconstructed from 40-channel scalp EEG in five patients during pre-surgical evaluation for focal drug-resistant epilepsy. Temporal Granger connectivity was estimated ten seconds before seizure and at seizure onset. Results have been analyzed using some centrality indices taken from Graph theory (Outdegree, Hubness). A new lateralization index is proposed by taking into account the sum of the most relevant hubness values across left and right regions of interest. ResultsIn three patients with positive surgical outcomes, analysis of the most relevant Hubness regions closely aligned with clinical hypotheses, demonstrating consistency in EZ lateralization and location. In one patient, the method provides unreliable results due to the abundant movement artifacts preceding the seizure. In a fifth patient with poor surgical outcome, the proposed method suggests a wider epileptic network compared with the clinically suspected EZ, providing intriguing new indications beyond those obtained with traditional electro-clinical analysis. ConclusionsThe proposed method could serve as an additional tool during pre-surgical non-invasive evaluation, complementing data obtained from EEG visual inspection. It represents a first step toward a more sophisticated analysis of seizure onset based on connectivity imbalances, electrical propagation, and graph theory principles.

Vagus nerve stimulation for epilepsy: A narrative review of factors predictive of response.

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy. However, there is a lack of reliable predictors of VNS response in clinical use. The identification of factors predictive of VNS response is important for patient selection and stratification as well as tailored stimulation programming. We conducted a narrative review of the existing literature on prognostic markers for VNS response using clinical, demographic, biochemical, and modality-specific information such as from electroencephalography (EEG), magnetoencephalography, and magnetic resonance imaging (MRI). No individual marker demonstrated sufficient predictive power for individual patients, although several have been suggested, with some promising initial findings. Combining markers from underresearched modalities such as T1-weighted MRI morphometrics and EEG may provide better strategies for treatment optimization.

Overcoming Graft Rejection in Induced Pluripotent Stem Cell-Derived Inhibitory Interneurons for Drug-Resistant Epilepsy.

Cell-based therapies for drug-resistant epilepsy using induced pluripotent stem cell-derived inhibitory interneurons are now in early-phase clinical trials, building on findings from trials in Parkinson's disease (PD) and Huntington's disease (HD). Graft rejection and the need for immunosuppressive therapy post-transplantation pose potential barriers to more epilepsy patients becoming potential candidates for inhibitory interneurons transplantation surgery. The present literature review weighs the evidence for and against human leukocyte antigen (HLA)-mediated graft rejection in PD and HD and examines the potential advantages and drawbacks to five broad approaches to cell-based therapies, including autologous cell culture and transplantation, in vivo reprogramming of glial cells using viral vectors, allogeneic transplantation using off-the-shelf cell lines, transplantation using inhibitory interneurons cultured from HLA-matched cell lines, and the use of hypoimmunogenic-induced pluripotent stem cell-derived inhibitory interneurons. The impact of surgical technique and associated needle trauma on graft rejection is also discussed. Non-systematic literature review. While cell-based therapies have enjoyed early successes in treating a host of central nervous system disorders, the immunologic reaction against surgical procedures and implanted materials has remained a major obstacle. Adapting cell-based therapies using iPSC-derived inhibitory interneurons for epilepsy surgery will similarly require surmounting the challenge of immunogenicity.

Amyloid deposition in adults with drug-resistant temporal lobe epilepsy.

Pathological amyloid-β (Aβ) accumulation and hyperphosphorylated tau proteins have been described in resected temporal lobe specimens of epilepsy patients. We aimed to determine cerebrospinal fluid (CSF) Aβ1-42 and p181-tau levels and cerebral Aβ deposits on positron emission tomography (Aβ PET) and correlate these findings with cognitive performance in adults with drug-resistant temporal lobe epilepsy (TLE). In this cross-sectional study, we enrolled individuals with drug-resistant TLE who were 25-55 years old. Each participant underwent 18F-flutemetamol PET, determination of CSF Aβ1-42, p181-tau, and total tau, and a comprehensive neuropsychological assessment. We evaluated normalized standard uptake value ratios (SUVRs) for different brain regions on Aβ PET. Thirty patients (mean age = 41.9 ± SD 8.1 years, 57% men) were included. The median disease duration was 9.5 (interquartile range = 4-24) years. Twenty-six patients (87%) had a clinically significant cognitive impairment on neuropsychological evaluation, 18 (69%) of the amnesic type. On Aβ PET, high uptake was observed in both mesial temporal regions (ipsilateral: SUVR z-score = .90, 95% confidence interval [CI] = .60-1.20; contralateral: SUVR z-score = .92, 95% CI = .57-1.27; p < .001), which was higher when compared to SUVR z-scores in all the remaining regions (p < .001) and in the ipsilateral anterior cingulate (SUVR z-score = .27, 95% CI = .04-.49, p = .020). No significant deposition was observed in other regions. Seven patients (23%) had low Aβ1-42 levels, and two (7%) had elevated p181-tau levels in CSF. Higher p181-tau levels correlated with poorer verbal fluency (R = -.427, p = .044). Our findings reveal a considerable Aβ deposition in mesial temporal regions and ipsilateral anterior cingulate among adults with drug-resistant TLE. Additionally, abnormal CSF Aβ1-42 levels were observed in a significant proportion of patients, and p181-tau levels were associated with verbal fluency. These results suggest that markers of neuronal damage can be observed in adults with TLE, warranting further investigation.

Anatomy-guided resections for paralimbic tumors in the temporo-insular region: combining tumor and epilepsy surgery concepts.

Tumors in the temporo-mesial region often extend into the insula and vice versa. The present study investigated the results of a surgical strategy that combines principles of tumor and epilepsy surgery. We retrospectively analyzed 157 consecutive patients with intrinsic brain tumors in the temporo-mesial region, with varying degrees of extensions into the insula (44 patients, 28.0%). The surgical strategy utilized "anatomy-guided resection," targeting specific anatomical compartments infiltrated by the tumor (e.g., temporal pole, anterior temporo-mesial region = uncus and hippocampal head, posterior temporo-mesial, insula) rather than treating the tumor as a single mass. The most frequent histologies were ganglioglioma CNS WHO grade 1 (55 patients, 35.0%) and IDH1 wildtype glioblastoma (36 patients, 22.9%). Tumor infiltration was most commonly found in the anterior temporo-mesial compartment (145 patients, 92.4%). An anterior temporal lobectomy was part of the surgical strategy in 131 cases (83.4%). Seventy-six patients (48.4%) with drug-resistant epilepsy underwent a formal presurgical epilepsy work-up, including depth electrode placement in three cases. Complete resections were achieved in 117 patients (74.5%), with supramarginal resections performed in 89 cases (56.7%). Four patients experienced non-temporary neurological complications (CTCAE grade 3-5). At 6 months, 127 of 147 assessable patients (86.4%) were free from seizures or auras (ILAE class 1), excluding early postoperative seizures (<30 days). At 24 months, 122 of 144 assessable cases (84.7%) remained seizure-free (ILAE class 1). Kaplan-Meier estimates for 5-year overall survival were 98.5% for non-recurrent glioneuronal tumors. The 2-year overall survival estimates were 96.0% for 24 primary diffuse CNS WHO grade 2 and 3 gliomas and 55.2% for 30 patients undergoing first surgeries for glioblastomas/astrocytomas CNS WHO grade 4. Combining both epilepsy and tumor surgery concepts in the surgical treatment of intrinsic brain tumors involving the mesial temporal lobe, often extending into the insula, led to more extensive resections, improved seizure outcomes, and potentially even better patient survival outcomes.

Assessment of the Efficacy of Deep Brain Stimulation (DBS) in Managing Drug-Resistant Epilepsy (DRE): A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs).

Epilepsy is a chronic neurological disorder affecting millions of people around the world. Even though the majority of patients gain seizure control with antiseizure medications (ASMs), many subjects may have drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) is a promising alternative, showing effectiveness in reducing seizures for some patients. This systematic review and meta-analysis aim to evaluate DBS's efficacy in DRE. A comprehensive search in PubMed, CENTRAL, Medline, Ovid, and Scopus was performed up to August 31, 2024, using the terms 'Drug-resistant Epilepsy' AND 'Deep Brain Stimulation'. Two independent researchers screened titles, abstracts, and full texts. The data extracted included study details, sample size, age at surgery, seizure duration, follow-up duration, seizure reduction (SR), responder rate (RR), and adverse events. Quality assessment was conducted using the Risk of Bias 2 (ROB2) tool (https://methods.cochrane.org/bias/resources/rob-2-revised-cochrane-risk-bias-tool-randomized-trials), and data analysis was performed using Jamovi software (https://www.jamovi.org). The search yielded 707 studies that were initially screened. Out of them, 29 articles were retrieved for full-text screening, and 5 randomized controlled trials (RCTs) were included in the review and meta-analysis. The meta-analysis showed that the pooled effect size for SR was 0.51 (95% CI, 0.35-0.68; P < 0.001), and the pooled effect size for RR was 0.54 (95% CI, 0.35-0.74; P < 0.001), demonstrating significant improvements in seizure control. The pooled effect size for adverse events was 0.21 (95% CI, 0.08-0.34; P = 0.001). The risk-of-bias assessment revealed a low risk of randomization for most studies. However, concerns were noted in areas such as deviations from the intended intervention and missing outcome data. In conclusion, DBS is a viable intervention for DRE, with significant reductions in seizure frequency and a favorable safety profile. However, the variability in efficacy and RRs across studies underscores the need for continued research to refine patient selection criteria, optimize stimulation parameters, and explore the differential effects of targeting various thalamic nuclei.

Unveiling the Potential of Gut Microbiota: Promising Approaches to Treat Drug-Resistant Epilepsy

Introduction: Epilepsy is a chronic, non-infectious disease of the brain. Data shows that even 70 million people worldwide suffer from it and one-third of them fail to control it with anti-epileptic drugs. The gut microbiota has an impact on the course of the disease. The microbiota mediates between the gastrointestinal system and the central nervous system.Purpose: The aim of the work is to analyse how modification of the gut microbiota affects patients with drug-resistant epilepsy.Material and method: In December 2023, an extensive search was conducted and articles found in the Medline (PubMed) databases were selected by using the following keywords: drug-resistant epilepsy, gut microbiota, gut-brain axis, ketogenic diet, probiotics, faecal microbiota transplantation, to focus on recent developments and advancements in the field, the search was limited to articles published between 2017 and 2023.Conclusions: The intestinal microbiota in drug-resistant epilepsy (DRE) patients differs from that of healthy individuals or drug-sensitive epilepsy patients. Acknowledging the presence of the gut-brain axis and its impact on the central nervous system, we can view altering the flora as a potential therapeutic approach for DRE patients. The ways in which microbiota changes have been confirmed by research include: ketogenic diet, antibiotics, probiotics and fecal microbiota transplantation (FMT). Modifying the microbiota through these mentioned methods is all promising for treating DRE.

Early mortality in STXBP1-related disorders.

Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders. Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease. We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13years (range: 11months-46years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018). We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies.

Deep Learning for Epileptic Seizure Detection Using a Causal-Spatio-Temporal Model Based on Transfer Entropy.

Drug-resistant epilepsy is frequent, persistent, and brings a heavy economic burden to patients and their families. Traditional epilepsy detection methods ignore the causal relationship of seizures and focus on a single time or spatial dimension, and the effect varies greatly in different patients. Therefore, it is necessary to research accurate automatic detection technology of epilepsy in different patients. We propose a causal-spatio-temporal graph attention network (CSTGAT), which uses transfer entropy (TE) to construct a causal graph between multiple channels, combining graph attention network (GAT) and bi-directional long short-term memory (BiLSTM) to capture temporal dynamic correlation and spatial topological structure information. The accuracy, specificity, and sensitivity of the SWEZ dataset were 97.24%, 97.92%, and 98.11%. The accuracy of the private dataset reached 98.55%. The effectiveness of each module was proven through ablation experiments and the impact of different network construction methods was compared. The experimental results indicate that the causal relationship network constructed by TE could accurately capture the information flow of epileptic seizures, and GAT and BiLSTM could capture spatiotemporal dynamic correlations. This model accurately captures causal relationships and spatiotemporal correlations on two datasets, and it overcomes the variability of epileptic seizures in different patients, which may contribute to clinical surgical planning.