Reduction In Seizure Frequency Research Articles

Efficacy of neuromodulation of the pulvinar nucleus for drug-resistant epilepsy.

The pulvinar nucleus of the thalamus has extensive cortical connections with the temporal, parietal, and occipital lobes. Deep brain stimulation (DBS) targeting the pulvinar nucleus, therefore, carries the potential for therapeutic benefit in patients with drug-resistant posterior quadrant epilepsy (PQE) and neocortical temporal lobe epilepsy (TLE). Here, we present a single-center experience of patients managed via bilateral DBS of the pulvinar nucleus. A single-institution retrospective review of five patients who underwent bilateral pulvinar DBS for drug-resistant TLE or PQE was performed. Stimulation parameters were adjusted monthly as needed, and side effects were monitored. The primary outcome was the percentage reduction in patient-reported seizure frequency in comparison to the preimplant baseline. The location of the active electrode contacts in relation to pulvinar thalami that produced the best seizure outcome was identified. Chronic sensing of the pulvinar local field potentials (LFPs) and circadian pattern of modulation of the LFP amplitudes were analyzed. Four patients (80%) experienced a >70% reduction in seizure frequency, whereas one patient had >50% reduction in seizure. Mean seizure reduction was 79% at a median follow-up of 13 months (range = 9-21 months). No significant side effects were noted. Of all the pulvinar subnuclei, stimulation of the medial pulvinar nucleus (MPN) produced the best seizure outcome in all patients except for two, in whom active contacts in the MPN but also in more lateral and inferior locations resulted in the most significant reduction in seizures. Chronic timeline data identified changes in LFP amplitude associated with stimulation and seizure occurrences. In this first ever report on a series of patients undergoing bilateral pulvinar DBS for drug-resistant epilepsy, we demonstrate that stimulation of the pulvinar and in particular the MPN is a safe and viable option for patients with nonlesional PQE or TLE. The optimal target for stimulation and relative merits of open versus closed loop stimulation should be delineated in future studies.

Ramadan fasting in adolescents with epilepsy: Seizure control and behavioral outcome.

Data about the effect of Ramadan fasting on seizure control among adolescents with epilepsy (AWE) is scarce. Several psycho-behavioral problems have also been encountered in this teenage group. This study aimed to assess seizure frequency and behavioral outcomes after Ramadan fasting in a sample of AWE METHODS: In this prospective study, AWE who completed fasting during Ramadan 2024 were evaluated regarding the seizure frequency of each type during Shaban (the month immediately preceding Ramadan) and Ramadan. Three questionnaires were requested to be answered at the end of two months. They were Patient Health Questionnaire (PHQ-9), Modified Overt Aggression Scale (MOAS), and Barratt Impulsiveness Scale-Short Form (BIS-11-SF) for assessment of depression, aggression, and impulsivity, respectively RESULTS: One hundred twenty AWE, with a median age of 15 and IQR 13-17, were evaluated. There was a statistically significant reduction in seizure frequency regarding focal onset seizures during Ramadan compared to Shaaban (P 0.009), as well as generalized non-motor (absence) seizures (P 0.027). The MOAS-total scores significantly reduced during Ramadan than Shaaban (P 0.003), as well as the scores of non-planning impulsivity of BIS-11-SF (P 0.005). On the other hand, depression assessed by PHQ-9 did not significantly differ between the two months CONCLUSION: Fasting Ramadan is associated with better control of multiple seizure types, including focal and generalized-onset non-motor (absence) seizures, besides psycho-behavioral aspects of aggression & non-planning impulsivity, without worsening of other seizure types nor depression, among AWE.

Factors associated with placebo response rate in randomized controlled trials of antiseizure medications for focal epilepsy.

Randomized controlled trials (RCTs) are necessary to evaluate the efficacy of novel treatments for epilepsy. However, there have been concerning increases in the placebo responder rate over time. To understand these trends, we evaluated features associated with increased placebo responder rate. Using individual-level data from 20 focal-onset seizure trials provided by seven pharmaceutical companies, we evaluated associations with change in seizure frequency in participants randomized to placebo. We used multivariable logistic regression to evaluate participant and study factors associated with differing rates of 50% reduction in seizure frequency during blinded placebo treatment, as compared to pre-randomization baseline seizure frequency. In addition, we focused on the association of placebo responder rate with pre-randomization baseline seizure frequency and country of recruitment. In the pooled analysis of 1674 participants randomized to placebo, a higher 50% responder rate (50RR) was associated with a shorter duration of epilepsy (p = .006), lower baseline seizure rate (p = .002), fewer concomitant antiseizure medications (p = .004), absence of adverse events (p < .001), more trial arms (p = .006), and geographic region (p < .001). Mixture modeling indicated a significantly higher 50RR in Bulgaria, Croatia, India, and Canada (42% in the higher group vs 22% in the lower group comprising all 40 other countries, p < 10-15). In addition, there was a significantly higher 50RR in participants with a baseline seizure frequency of six or fewer seizures per 28 days (29% vs 21%, p = .00018). These results can assist future RCTs in estimating the expected placebo responder rate, which may lead to more reliable power estimates. Higher placebo responder rate was associated with markers of less-refractory epilepsy. There were concerning significant differences in placebo responder rate by country and geographic region as well as an elevated placebo responder rate in participants with baseline seizure frequency close to the minimum eligibility criteria.

Community-based epilepsy care in an onchocerciasis-endemic area: A 3-year cohort study in Mahenge, Tanzania.

In onchocerciasis-endemic areas, limited access to antiseizure medications (ASMs) contributes to a high epilepsy burden. This study evaluated the impact of a community-based epilepsy care program in Mahenge, Tanzania, an onchocerciasis-endemic area with high epilepsy prevalence. A baseline survey (2017-2018) identified persons with epilepsy (PWE) in four rural villages. Subsequently, PWE were invited to enroll in the epilepsy treatment program (2019-2022), where trained community health workers (CHWs) screened for epilepsy, promoted ivermectin intake to treat onchocerciasis, distributed ASMs, and monitored seizure frequency and ASM adherence monthly under supervision from the project clinician trained in epilepsy diagnosis and treatment. A concluding survey (2022) collected sociodemographic data and participants' status as alive, deceased, or lost to follow-up. Mixed-effects negative binomial regression analyzed risk factors for weekly seizure incidence rate. Of 206 participants, 77.7% reported bilateral tonic-clonic seizures, and 32.0% reported focal seizures. More than one third (38.5%) were suspected of having nodding syndrome. Weekly seizure frequency decreased significantly from a mean of 1.9 seizures (interquartile range [IQR] = 0-2) at enrollment to .4 seizures (IQR = 0-0) at the last follow-up (Wilcoxon test p < .0001), with significantly improved ASM adherence (57.5%-94.7%, McNemar test p < .0001). Factors associated with lower weekly seizure incidence included longer program participation, ASM adherence, carbamazepine use compared to phenobarbital, and ivermectin intake in 2022. ASM adverse events were associated with increased seizure frequency. The mortality rate was 32.7 deaths per 1000 person-years, with most deceased not fully adhering to ASM (88%) and having epilepsy-related causes of death (60%). The community-based program using CHWs was associated with a significant reduction in seizure frequency and improved ASM adherence. In onchocerciasis-endemic areas, it should be investigated whether carbamazepine should be a preferred ASM in PWE. Ivermectin's impact on seizure frequency merits further investigation in onchocerciasis-endemic areas. Community-based epilepsy care is a promising strategy for scaling up epilepsy care in rural areas in Africa.

Decreased neuronal excitability in hypertriglyceridemia hamsters with acute seizures.

Neonatal seizures are the most common clinical manifestation of neurological dysfunction in newborns, with an incidence ranging from 1 to 5‰. However, the therapeutic efficacy of current pharmacological treatments remains suboptimal. This study aims to utilize genetically modified hamsters with hypertriglyceridaemia (HTG) to investigate the effects of elevated triglycerides on neuronal excitability and to elucidate the underlying mechanisms. The ultimate goal is to identify novel therapeutic targets for the treatment of neonatal seizures. Acute seizure models were established both in vivo and ex vivo using wild-type and Apolipoprotein C2 knockout (Apoc2 -/-) hamsters. The frequency of tonic-clonic seizures was recorded. Excitatory postsynaptic potentials (EPSPs) and evoked action potentials (eAPs) of pyramidal neurons in the frontal cortex were measured. Fatty acid metabolomic analysis was conducted on microdialysate from the frontal cortex tissue post-seizure, and mRNA expression changes were also assessed. Apoc2 -/- hamsters exhibited a reduced frequency of tonic-clonic seizures and diminished EPSP and eAP in comparison to wild-type hamsters. Following seizure induction, free palmitic acid levels in the frontal cortex dialysate significantly decreased, while the expression of palmitoyl acyltransferase 14 (ZDHHC14) in the frontal cortex tissue was higher in Apoc2 -/- hamsters than in wild-type hamsters. Additionally, the amplitude of transient outward potassium currents (IA) in cortical neurons of Apoc2 -/- hamsters was observed to be elevated compared to wild-type hamsters. Hypertriglyceridemic Apoc2 -/- hamsters exhibited reduced seizure frequency and decreased cortical neuron excitability. The upregulation of ZDHHC14, leading to increased IA, may be a crucial mechanism underlying the observed seizure protection.

Epilepsy Surgery for Drug-Resistant Epilepsy in Africa: A Systematic Review.

Nearly one-third of individuals with epilepsy have drug-resistant epilepsy, treated most effectively with surgery. This study aims to discuss the demographic profile, surgical access, and strategies used in drug-resistant epilepsy in Africa. A systematic review was performed using PubMed, Google Scholar, Embase, and Web of Science in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Nine studies encompassing 498 patients from 6 African countries (Egypt, Kenya, Morocco, South Africa, Tunisia, and Uganda) were included. The mean Methodological Index for Non-Randomized Studies score for these articles was 9.6 ± 1.6. The average patient age was 24.9 years (95% CI: 18.9-30.8 years), with a male predominance of 53.4%. The average age of seizure onset was 10.4 years (95% CI: 6.1-14.7 years). Most patients experienced focal onset seizures (73.1%), with head trauma (33.1%) being the most reported risk factor. The predominant etiologies were hippocampal sclerosis (66.8%, 95% CI: 42.7-91), microdysgenesis (26.7%, 95% CI: 20.7-32.7), and brain tumors (22.3%, 95% CI: 6.4-38.2). Lesions were primarily located in the left hemisphere (61.9%, 95% CI: 26.7-97.1), with temporal lobe involvement in 54.8% of cases (95% CI: 28.7-80.8). Temporal lobectomy was the most frequently performed surgery (59.6%), followed by lesionectomy (9.6%). Postoperatively, 80.6% of patients achieved Engel class I outcomes, indicating seizure freedom, and long-term follow-up (1 to 5 years) showed that 70.3% maintained Engel class I outcomes. Surgical complications were reported in 8.8% of cases. These findings demonstrate the efficacy and long-term benefits of epilepsy surgery in Africa, where epilepsy is a significant public health challenge. The high rates of seizure freedom and reduced seizure frequency from surgery highlight its potential to improve the quality of life for individuals with drug-resistant epilepsy in Africa.

Medial pulvinar stimulation for focal drug-resistant epilepsy: interim 12-month results of the PULSE study

ObjectiveThis study aims to evaluate the efficacy and safety of deep brain stimulation (DBS) of the medial pulvinar nucleus (PuM) in reducing seizure frequency and addressing comorbidities in patients with drug and vagal nerve-resistant focal epilepsy.MethodsThis is an open-label prospective treatment trial with a planned enrollment of 12 patients suffering from medically refractory epilepsy (Clinical trial gov NCT04692701), for which the interim 12-month post-implantation results for the first 6 patients are being reported. Inclusion criteria were focal epilepsy not suitable for or after failed surgical intervention and previous failure of neurostimulation therapies (vagus nerve stimulation or anterior thalamic nucleus DBS). Evaluations included seizure diaries, neuropsychological assessments, and scales for depression, anxiety, quality of life, and seizure severity. PuM DBS was performed using ROSA robotic assistance, with follow-ups every 3 months for 1 year.ResultsOut of six patients, five completed 1-year follow-up (one patient died prematurely). A non-significant trend toward seizure reduction was observed at 6 months, becoming more pronounced at 1 year (mean reduction: 45%; responders: 2/5). Seizure severity significantly improved (p = 0.02), with a reduction in the NHS3 scale scores. Quality of life improved significantly at 1 year (p = 0.03). Psychiatric assessments indicated a non-significant trend toward improvement in depression (mean improvement: 26%) and anxiety (mean improvement: 20%) scores. Neuropsychological testing showed stable or improved cognitive performance in three out of five patients. Adverse events included one case of cerebral hemorrhage, one infection leading to device removal, and one possible SUDEP.SignificancePreliminary results suggest that PuM DBS may offer a promising therapeutic option for reducing seizure severity and improving quality of life and cognitive functions in patients with drug-resistant epilepsy. Despite the small sample size and the presence of serious adverse events, the findings warrant further investigation with larger cohorts to confirm these trends and optimize the treatment protocol.

Survey of Latin American ketogenic diet centers: Challenges and success for "La Terapia Cetogénica".

Despite growing recognition of the efficacy of ketogenic diet therapies (KDT) in reducing seizure frequency and improving the quality of life for individuals with epilepsy, several factors hinder their widespread adoption across Latin America. Specific challenges in the region have been discussed but not formally studied. Currently, no data exist on the availability and operation of KDT teams in the region. To address this gap, we conducted a survey of KDT centers across Latin American countries in the framework of the biannual International Ketogenic Diet Conference in September 2023. A seven-question survey was distributed via email to neurologists, dietitians, or through indexed publications. Of the 16 centers approached, 14 (87.5%) responded, identifying 98 KDT centers. Nearly half (49%) are public institutions, primarily in Brazil, Chile, and Mexico; 44 are private; and 5 are mixed. Core teams in all centers included a neurologist and dietitian, with some teams in Argentina, Chile, and Paraguay also involving a medical nutritionist. None of the centers reported a protocol for transitioning to adult care, and consistent data on Glut1 patients and protocols were lacking. Over the past two decades, the KDT landscape in Latin America has improved, with established centers expanding and new ones emerging. However, continued efforts are needed to promote KDT adoption in countries where it is not yet practiced and in regions with limited resources and expertise.

Epilepsy surgery in children with operculoinsular epilepsy: Results of a large unicentric cohort.

Epilepsy surgery in the operculoinsular cortex is challenging due to the difficult delineation of the epileptogenic zone and the high risk of postoperative deficits. Pre- and postsurgical data from 30 pediatric patients who underwent operculoinsular cortex surgery at the Motol Epilepsy Center Prague from 2010 to 2022 were analyzed. Focal cortical dysplasia (FCD; n = 15, 50%) was the predominant cause of epilepsy, followed by epilepsy-associated tumors (n = 5, 17%) and tuberous sclerosis complex (n = 2, 7%). In eight patients where FCD was the most likely etiology, the histology was negative. Seven patients (23%) displayed normal magnetic resonance imaging results. Seizures exhibited diverse semiology and propagation patterns (frontal, perisylvian, and temporal). The ictal and interictal electroencephalographic (EEG) findings were mostly extensive. Multimodal imaging and advanced postprocessing were frequently used. Stereo-EEG was used for localizing the epileptogenic zone and eloquent cortex in 23 patients (77%). Oblique electrodes were used as guides for better neurosurgeon orientation. The epileptogenic zone was in the dominant hemisphere in 16 patients. At the 2-year follow-up, 22 patients (73%) were completely seizure-free, and eight (27%) experienced a seizure frequency reduction of >50% (International League Against Epilepsy class 3 and 4). Fourteen patients (47%) underwent antiseizure medication tapering; treatment was completely withdrawn in two (7%). Nineteen patients (63%) remained seizure-free following the definitive outcome assessment (median = 6 years 5 months, range = 2 years to 13 years 5 months postsurgery). Six patients (20%) experienced corona radiata or basal ganglia ischemia; four (13%) improved to mild and one (3%) to moderate hemiparesis. Two patients (7%) operated on in the anterior insula along with frontotemporal resection experienced major complications: pontine ischemia and postoperative brain edema. Epilepsy surgery in the operculoinsular cortex can lead to excellent patient outcomes. A comprehensive diagnostic approach is crucial for surgical success. Rehabilitation brings a great chance for significant recovery of postoperative deficits.

Cenobamate, a New Promising Antiseizure Medication: Experimental and Clinical Aspects.

About 40-50% of patients with drug-resistant epilepsy do not properly respond to pharmacological therapy with antiseizure medications (ASMs). Recently approved by the US Food and Drug Administration and European Medicines Agency as an add-on drug for focal seizures, cenobamate is an ASM sharing two basic mechanisms of action and exhibiting a promising profile of clinical efficacy. The drug preferably inhibits persistent sodium current and activates GABA-mediated events via extrasynaptic, non-benzodiazepine receptors. Thus, its antiseizure potential is dependent on both reducing excitation and enhancing inhibition in the central nervous system. In experimental seizure models, cenobamate exhibited a clear-cut activity in many of them with promising protective indexes, with only bicuculline-induced seizures being unaffected. Randomized clinical trials indicate that combinations of cenobamate, with already prescribed ASMs, resulted in significant percentages of seizure-free patients and patients with a significant reduction in seizure frequency, compared to other ASMs in the form of an add-on therapy. Its greater antiseizure efficacy was accompanied by adverse events comparable to other ASMs. Cenobamate has also been shown to possess neuroprotective activity, which may be of importance in affecting the process of epileptogenesis and, thus, modifying the course of epilepsy.

Sturge-Weber syndrome: updates in translational neurology.

Sturge-Weber syndrome (SWS) is a rare congenital neurovascular disorder that initially presents with a facial port-wine birthmark (PWB) and most commonly associated with a R183Q somatic mosaic mutation in the gene GNAQ. This mutation is enriched in endothelial cells. Contrast-enhanced magnetic resonance imaging (MRI) diagnoses brain abnormalities including leptomeningeal vascular malformation, an enlarged choroid plexus, and abnormal cortical and subcortical blood vessels. Mouse SWS models identify dysregulated proteins important for abnormal vasculogenesis and blood brain barrier permeability. Recent clinical research has focused on early diagnosis, biomarker development, presymptomatic treatment, and development of novel treatment strategies. Prospective pilot clinical drug trials with cannabidiol (Epidiolex) or with sirolimus, an mTOR inhibitor, indicate possible reductions in seizure frequency and improved cognitive outcome. This review connects the most recent molecular research in SWS cell culture and animal models to developing new treatment methods and identifies future areas of research.

Long-Term Seizure Outcome With or Without Vagal Nerve Stimulation Therapy.

To compare long-term seizure control in patients with long-term VNS (vagal nerve stimulator) stimulation (VNS-on) with those who discontinued VNS after >3 years (VNS-off). Patients with refractory epilepsy with VNS therapy for >3 years (and follow-up for >2 years after VNS discontinuation for VNS-off patients) were included. Patients with brain surgery <3 years after VNS were excluded. We compared the percentage of patients with ≥50% seizure reduction (50% responder rate) and change in seizure frequency within and between groups in follow-up. Thirty-three VNS-on and 16 VNS-off patients were evaluated. VNS-on patients underwent stimulation for 9.7 years (mean). VNS-off patients had VNS treatment for 6.5 years (mean), discontinued treatment, then had additional 8.0 years (mean) follow-up. 50% responder rates were similar between groups (VNS-on: 54.5% vs VNS-off at last-on: 37.5%, p = 0.26; vs VNS-off at the last follow-up: 62.5%, p = 0.60). VNS-on patients had a significant reduction in seizure frequency at the last follow-up compared with baseline (median [Mdn] = -4.5 seizures/month, interquartile range [IQR] = 14.0, 56% reduction, p = 0.013). VNS-off patients also showed significant seizure reduction while still continuing VNS therapy (Mdn = -1.0 seizures/month, IQR = 13.0, 35% reduction, p = 0.020) and, after discontinuing therapy, at the last follow-up compared with baseline (Mdn = -3.2, IQR = 11.0, 52% reduction, p = 0.020). The 2 groups were comparable in seizure frequency change both at the last-on visit (absolute change, p = 0.62; relative change, p = 0.50) at the last follow-up (absolute change, p = 0.67; relative change, p = 0.76). Patients who discontinued VNS therapy and those who continued therapy had similar response during active treatment and similar long-term outcomes, suggesting that factors such as the natural disease course and/or medication treatment strongly affect long-term outcomes.

Altered gut microbiome profiles in epileptic children are associated with spectrum of anti-seizure medication responsiveness

Gut microbiota plays a role in epilepsy. However, current knowledge of how gut dysbiosis is associated with a response to anti-seizure medications (ASMs) in epileptic children is still limited. We aimed to characterize the gut microbiota profiles in epileptic children based on response to ASMs. Eighty-six children aged 3–18 years old with a regular oral diet were enrolled onto the study and divided into three groups in accordance with ILAE definitions: 26 healthy controls, 31 drug-sensitive epilepsy (DSE) patients, and 29 drug-resistant epilepsy (DRE) patients. Based on ASM responsiveness, defined as a reduction in seizure frequency of at least 75 % over one year, DRE individuals were subclassified into 13 drug responsive (DRE-DR) and 16 drug non-responsive (DRE-DNR) patients. Feces were collected at the time of enrollment for gut microbiota analysis using 16S rRNA sequencing. Epileptic patients exhibited distinctive gut dysbiotic profiles. Differential abundance investigation revealed that CAG-56 was significantly increased in epileptic patients compared to controls. Saccharimonadales and Peptoclostridium significantly increased in the DSE group, compared to the DRE group. Vibrionaceae, especially Grimontia, Rhodobacteraceae, and Enterobacter were significantly abundant in the DRE-DNR group, followed by abundance in the DRE-DR and DSE groups. Outcomes from PICRUSt2 analysis predicted that epileptic patients, especially those in the DRE group, had increased metabolic pathways responsible for vanillin and taurine degradation, compared to controls. These findings suggest that gut dysbiosis could play roles in epileptogenesis and ASM resistance. Notably, the identified gut microbes could serve as predictive biomarkers for the DRE condition.

AI-Enabled Neural Stabilizer Devices: A Theoretical Novel Approach to Correcting Pathological Brain Waves in Neurological Disorders

This article explores the development and potential applications of AI-enabled neural stabilizer devices in treating neurological and psychiatric conditions characterized by pathological brain waves, such as drug-resistant epilepsy. By integrating advanced artificial intelligence with neurostimulation technology, these devices continuously monitor brain activity through implanted electrodes, analyze neural signals in real-time to detect abnormal patterns, and deliver targeted electrical stimulation to disrupt pathological activity before or just after it manifests as clinical symptoms. The use of machine learning algorithms allows for personalized treatment tailored to the individual's unique neural patterns, enhancing the effectiveness of interventions. Clinical studies have demonstrated the efficacy of responsive neurostimulation systems in reducing seizure frequency among patients with refractory epilepsy. Beyond epilepsy, the potential applications extend to conditions like depression, obsessive-compulsive disorder, Tourette's syndrome, Parkinson's disease, and chronic pain. The article also addresses the ethical, technical, and regulatory challenges associated with implementing such advanced technology, emphasizing the need for interdisciplinary collaboration to realize the full potential of this innovative approach.

Early assessment of responsive neurostimulation for drug-resistant epilepsy in China: A multicenter, self-controlled study.

To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (EpilcureTM, GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariate linear regression was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. The follow-up period for the 19 participants was 10.7±3.4months. Seizure counts decreased significantly 6months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 (P<0.05). The average response rate after 13months of treatment was 42%, with 21% (n=4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 (β<0, P<0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. The preliminary findings suggest that EpilcureTM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. Chinese Clinical Trial Registry (No. ChiCTR2200055247).

Vagal Nerve Stimulation in the Pediatric Population and Correlation between Family and Treatment Team Perspectives: Single-Center Experience.

Vagal nerve stimulation (VNS) is an adjunctive therapy to pharmacologic treatment in patients with drug-resistant epilepsy. This study aimed to assess the efficacy of VNS therapy for seizure frequency reduction and improving the quality-of-life (QOL) measures in children with refractory epilepsy and to evaluate the correlation between the perspectives of families and those of the treating team. This was a prospective cohort study conducted at Abha Maternity and Children's Hospital, Saudi Arabia, from 2018 to 2022. A total of 21 pediatric patients who completed 1 year of follow-up after VNS implantation were included. Patients were aged between 2 and 14 years, with a mean age of 8.14 ± 3.92 years; 11 (52.4%) patients were females. Family and physician assessments were collected blinded to each other using the Clinical Global Impression of Improvement (CGI-I) scores and QOL assessments to evaluate the correlation between the families' and treating team's perspectives on VNS outcomes. In this study, VNS showed significant efficacy in reducing the frequency of seizures. VNS significantly reduced the number of seizures per week from a baseline median of 35 to a median of 0.25 at the end of the follow-up period, representing a dramatic reduction of 99.3% (p < 0.001). The number of emergency department visits per year decreased from a baseline median of 12 to a median of 2, a reduction of 83.3% (p < 0.001), while the number of hospital admissions per year decreased from a baseline median of 3 to a median of 1, a 66.7% decrease (p < 0.001). The number of antiepileptic medications taken decreased from a median of four to three (p < 0.001). Notably, 28.57% of the patients achieved complete seizure freedom, and 38% exhibited significant improvement, with at least 50% reduction in seizure frequency. Importantly, none of the patients experienced an increase in seizure frequency following VNS treatment. The family and physician assessments showed varying degrees of alignment in perceptions, with "concentration" exhibiting a significant positive correlation (r = 0.498, p = 0.022), indicating noteworthy agreement, whereas verbal communication did not show a substantial correlation (r = - 0.062, p = 0.791), indicating a divergence of views. VNS is a promising and well-tolerated therapy for individuals with intractable seizures, offering clinical benefits and potential enhancements in various aspects of QOL. The varying perceptions between family and physician assessments highlight the importance of considering multiple perspectives when evaluating treatment outcomes.

Mechanisms of Epilepsy and Efficacy of Neuroplasticity-Based Treatment

Epilepsy is a neurological disorder characterized by the development of trauma to the nervous system and recurrent seizures. Neuroplasticity, the ability of the nervous system to reorganize its structure and function in response to trauma, plays a crucial role in the development and treatment of epilepsy. Several recent studies have mentioned the potential of treating epilepsy based on neuroplasticity, such as deep brain stimulation (DBS), neurofeedback and non-invasive brain stimulation techniques. While conventional treatments focus primarily on seizure control, neuroplasticity interventions aim to alter neural circuits, reduce seizure frequency and severity, and may ameliorate the effects caused by the sequelae of epilepsy. There are already a number of therapies for epilepsy that incorporate neuroplasticity, which provides a basis for subsequent research. This paper explores the pathogenesis of epilepsy with a focus on the role of neuroplasticity in the onset and progression of epilepsy. However, further research is needed to optimize these approaches and fully understand their therapeutic potential.

Ivermectin as a promising therapeutic option for onchocerciasis-associated epilepsy.

Onchocerciasis, commonly known as river blindness, is a neglected tropical disease caused by the parasite Onchocerca volvulus. It can lead to blindness and visual impairment. Studies have also demonstrated a link between onchocerciasis and epilepsy, with there being a correlation between onchocerciasis endemicity and epilepsy prevalence. Onchocerciasis-associated epilepsy (OAE) emerges predominantly in individuals aged 3-18, with a notable prevalence in regions where onchocerciasis transmission persists. These areas exhibit elevated rates of epilepsy, underscoring the significant impact of ongoing onchocerciasis on the incidence of epilepsy, particularly within the specified age range. Both epilepsy prevalence and incidence have evolved over the past three decades in a Tanzanian area endemic for onchocerciasis. Researchers have studied the effects of the antiparasitic drug ivermectin on OAE. About one third of Ugandan patients saw reduced seizure frequency or intensity after one 150 μg/kg dose. Clinical research in the Congo among infected epileptics on anti-seizure medications (ASMs) suggested ivermectin may decrease seizure frequency following oral administration of ivermectin tablets (3 mg). Beyond its antiparasitic properties, ivermectin has demonstrated anticonvulsant effects against clonic and tonic-clonic seizures, likely through modulation of GABAA receptor and neuroinflammation. There is evidence of synergistic effects when combined with GABAergic ASMs like diazepam. As neuroinflammation plays a key role in OAE, ivermectin's anti-inflammatory properties by inhibiting cytokines like TNF-α and IL-1β are also relevant. While certain other antiparasitic drugs can interact with ASMs and have side effects like seizures, no such interactions or side effects have been reported for ivermectin. However, there is a need for more randomized controlled trials specifically evaluating ivermectin's impact on seizures in O. volvulus-infected epileptics on ASMs. Given its efficacy against parasites, limited side effects, and potential anticonvulsant mechanisms, ivermectin could be a favorable first-line treatment option, but further research is warranted to confirm benefits for OAE. PLAIN LANGUAGE SUMMARY: This article explores the potential benefits of ivermectin, a drug commonly used to treat parasitic infections, for reducing seizures in people with epilepsy linked to onchocerciasis, also known as river blindness. Research shows that ivermectin not only targets the parasitic cause of the disease but may also help reduce brain inflammation, which plays a key role in epilepsy. While early results are promising, more research is needed to confirm whether ivermectin can be a reliable treatment for epilepsy in people affected by this condition.

Efficacy and safety of perampanel in patients with seizures associated with Lennox-Gastaut syndrome: A randomized trial.

The Phase 3 Study 338 (NCT02834793) assessed long-term clinical outcomes of adjunctive perampanel in patients ≥2 years of age with uncontrolled seizures associated with Lennox-Gastaut syndrome (LGS). Eligible patients were diagnosed with LGS and receiving one to four concomitant antiseizure medications with an average of two or more drop seizures/week during baseline. The study comprised an 18-week double-blind, randomized, placebo-controlled Core Study and ≥52-week open-label Extension. The primary endpoint was median percent change in drop seizure frequency per 28 days during the Core Study. Key secondary endpoints included responder rates, seizure-freedom rates, and safety outcomes. Post hoc analyses were performed encompassing a broader range of drop seizures or all countable motor seizures. Seventy patients were randomized into the Core Study (perampanel, n = 34; placebo, n = 36), and 58 entered the Extension. In the Core Study, numerically greater median percent reductions in drop seizure frequency were observed with perampanel (23.1%) vs placebo (4.5%) using prespecified assessments (p = .107), whereas significantly greater reductions were detected using the broader definition (48.6% vs -.7%, respectively, p = .001) or all countable motor seizures (44.0% vs -.6%, respectively, p = .017). The 50% responder rate for drop seizures was higher with perampanel vs placebo using modern definitions. Reductions in seizure frequency with perampanel were maintained over 52 weeks. Treatment-emergent adverse events occurred in 85.3% of perampanel-treated patients (somnolence [23.5%] was the most frequent) and 72.2% of placebo-treated patients. This study had a reduced sample size and was underpowered. Although the difference in reductions in drop seizure frequency between treatments was not statistically significant by prespecified assessments, adjunctive perampanel demonstrated sustained efficacy in reducing drop seizures associated with LGS for ≤71 weeks using modern definitions. No new safety signals emerged. These observations suggest the long-term efficacy and safety of perampanel in the LGS population.

Efficacy and safety of deep brain stimulation in drug resistance epilepsy: A systematic review and meta-analysis.

In the context of drug-resistant epilepsy, deep brain stimulation (DBS) has received FDA approval. However, there have been reports of potential adverse effects, such as depression and memory impairment associated with DBS.This systematic review and meta-analysis aimed to investigate the impact of DBS on the quality of life (QoL), and seizure frequency of patients who had DRE, and assess its potential adverse events. The study followed PRISMA guidelines and thoroughly assessed databases, including Pubmed, Scopus, Embase, Web of Science, and the Cochrane Library, up to 31 July. Statistical analysis, fixed effect model analysis, performed by the Comprehensive Meta-analysis software (CMA) version 3.0. Additionally, Cochran's Q test was conducted to determine the statistical heterogeneity. The systematic review encompassed 54 studies, with 38 studies included in the subsequent meta-analysis. The total number of patients included in the studies was 999. The findings indicated a significant decrease in the mean seizure frequency of subjects following DBS (SMD: 0.609, 95% CI: 0.519 to 0.700, p-value < 0.001). Moreover, patients' QoL significantly improved after DBS (SMD: -0.442, 95% CI: -0.576 to -0.308, p-value < 0.001). The hippocampus displayed the most notable effect size among the different DBS targets. Subgroup analysis based on follow-up duration revealed increased DBS efficacy after two years. There are few reports of adverse events, such as insertional-related complications, infection, and neuropsychiatric complications, but the majority of these were temporary and non-fatal. DBS emerged as an effective and safe procedure for reducing seizure frequency and enhancing the quality of life in DRE patients, with minimal adverse events. Furthermore, the efficacy of DBS was observed to improve over time.