Seizure Frequency Research Articles

Testing an online screening tool for epilepsy surgery evaluation.

Epilepsy surgery is recognized for its effectiveness in controlling seizures in a significant number of patients with drug-resistant epilepsy. Despite this, there remains a notable deficiency in referring these patients for video-electroencephalogram (EEG) monitoring and surgical evaluation. Addressing this gap, the Canadian Appropriateness of Epilepsy Surgery (CASES), an online tool for epilepsy surgery evaluation (www.epilepsycases.com), was developed to aid physicians in the referral process of patients with refractory epilepsy to surgical assessments. The present study aimed to evaluate the utility of CASES in identifying candidates for epilepsy surgery, thereby facilitating clinical decision-making for patients with drug-resistant epilepsy. A cross-sectional analysis was conducted using the CASES platform to assess surgical candidacy among individuals with epilepsy. Participants were selected among those receiving care at the Epilepsy Clinic of the Neurology Service, Hospital de Clínicas de Porto Alegre, Brazil, over a 3-month period. The study cohort included 211 patients. Data were systematically extracted from patient medical records or collected during clinical appointments. Of the evaluated cohort, 59.6% were identified as potential candidates for video-EEG monitoring and subsequent surgical evaluation. Factors significantly associated with recommendations for video-EEG and surgical assessment included seizure frequency, the number of antiseizure medications (ASMs) trialed, and the occurrence of drug-related adverse effects. The CASES showed significant potential in guiding recommendations for video-EEG monitoring and facilitating referrals for epilepsy surgery. This tool may not only enhance patient treatments and outcomes but also contribute to cost savings in epilepsy management in both the short and long term.

Deep brain stimulation of the subthalamic nucleus for a patient with drug resistant juvenile myoclonic epilepsy: 1year follow-up.

Drug-resistant juvenile myoclonic epilepsy (DR-JME) remains a significant challenge in neurology. Traditional management strategies often fail to achieve satisfactory control, necessitating innovative treatments. This case report aims to evaluate the efficacy and safety of deep brain stimulation (DBS) targeting the subthalamic nucleus (STN-DBS) in a patient with DR-JME. We describe the treatment of a patient with DR-JME using STN-DBS. The patient underwent implantation and received high-frequency stimulation (HFS) at the STN. One year post-implantation, the patient demonstrated a substantial reduction in motor seizure frequency by 87.5%, with improvements in quality of life and seizure severity by 52.0% and 46.7%, respectively. No adverse events were reported during the follow-up period. This case represents the first report of favorable outcomes with STN-DBS in a patient with DR-JME, suggesting that long-term HFS of the STN may be a promising treatment option for patients suffering from this condition.

Efficacy and safety of ketogenic diet in infants with epilepsy: KIWE RCT

Background Many infancy-onset epilepsies have a poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in older children and adults unresponsive to antiseizure medicines. We aimed to determine the effectiveness of the ketogenic diet in reducing seizure frequency compared to further antiseizure medicine in infants with drug-resistant epilepsy. Methods In this randomised, open-label trial, 136 infants with epilepsy, aged 1–24 months, with > 4 seizures/week and a previous trial of ≥ 2 antiseizure medicines were recruited from 19 hospitals in the United Kingdom. Following a 1- or 2-week observation period, participants were randomised to receive the classical ketogenic diet or a further antiseizure medicine for 8 weeks, using a computer-generated schedule without stratification. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). Findings Between 1 January 2015 and 30 September 2021, 136 eligible infants were randomised. Sixty-one (78%) of 78 assigned to a ketogenic diet and 47 (81%) of 58 assigned to antiseizure medicine had primary outcome data. At 8 weeks, the number of seizures per day, accounting for the baseline rate and randomised group, was not significantly different between groups [median (interquartile range) ketogenic diet 5 (1, 16); antiseizure medicine 3 (2, 11), incidence rate ratio 1.33, 95%, confidence internal 0.84 to 2.11; p = 0.22]. A similar number of infants reported at least one serious adverse event in both groups [antiseizure medicine: 24/56 (43%), ketogenic diet: 40/78 (51%)]. The most common serious adverse events were seizures in both groups. Three infants died during the course of the trial, all of whom were randomised to the ketogenic diet arm; deaths were considered to be unrelated to treatment. Interpretation There was no evidence that a ketogenic diet was better than further antiseizure medicine in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and a ketogenic diet appears safe to use in infants with epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite trial of two standard antiseizure medicines. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information.

Ketogenic Diet as a Therapeutic Intervention for Doose Syndrome: A Case Report and Review of Current Evidence

Epilepsy with myoclonic-atonic seizures, also known as Doose syndrome or myoclonic–astatic epilepsy (MAE), represents a challenging pediatric epilepsy syndrome, initially described by Doose et al. in 1970. MAE accounts for 1%–2.2% of juvenile-onset epilepsy cases, characterized by normal early development, followed by seizure onset between 7 months and 6 years. Seizure types include myoclonic, myoclonic-atonic, generalized tonic–clonic, and atypical absences, often accompanied by nonconvulsive status epilepticus. Electroencephalogram typically shows parietal-dominant rhythmic theta activity or a posterior 4 Hz pattern. While conventional antiseizure medications (ASMs) offer some efficacy, outcomes vary widely, and up to 50% of patients may experience refractory seizures and poor intellectual outcomes. The ketogenic diet (KD), a high-fat, low-carbohydrate diet inducing ketosis, has shown promise in reducing seizure frequency and severity in refractory epilepsy, including MAE. This case report describes a successful outcome with a South Indian style KD in a 3-year-old boy with Doose syndrome presenting with 20–25 daily head drop seizures despite multiple ASMs and steroid therapy. Initiation of a home-based KD utilizing traditional household ingredients significantly reduced seizure frequency by 60% within 1 month and 80% within 2 months and was 100% seizure-free in 3rd month following KD, alongside developmental improvements. The KD was well-tolerated, with improved nutritional status. This case underscores KD’s potential as a viable complementary therapy for MAE, emphasizing the need for ongoing parental support and supervision to ensure dietary adherence and optimize outcomes. It is commonly believed that the KD is challenging for the South Indian population to follow due to the high carbohydrate content in South Indian cuisine. However, this case demonstrates that a KD can indeed be tailored around South Indian dishes, highlighting the uniqueness of this approach. When the diet is customized to consider a child’s dietary habits, culture, and cuisine, it becomes easier to follow over the long term, leading to effective seizure control. Further research is necessary to refine dietary protocols and evaluate long-term efficacy in MAE management.

Variants loci and phenotype correlation of TRIM8-related neuro-renal syndrome: three cases reports and literature review.

TRIM8-related neuro-renal syndrome (NRS), caused by pathogenic variants of the TRIM8 gene, is characterized by epilepsy, developmental delay (DD) and renal disorders. The severity of the neurological effects as well as the presence of renal disorders is variable among patients. Here, we report three additional patients with clinical features compatible with NRS and summarize the association between the variants' loci and phenotype of TIRM8-related NRS. A retrospective analysis was conducted for three Chinese children with NRS due to TRIM8 variants identified through whole-exome sequencing (WES). Previous reports of patients with TRIM8-related NRS were reviewed systematically. Demographic and clinical data were collected from these patients. Two de novo TRIM8 truncating variants in three NRS patients were identified in our study, including c.1327_c.1328delCCinsTG (p. Arg443*) and c.1375C>T (p.Gln459*). Our three patients all exhibited drug-resistant epilepsy and early-onset DD, and two of whom developed electrical status epilepticus during sleep (ESES). Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia in one patient and normal in the other two. All three patients demonstrated nephrotic range proteinuria (NRP) or nephrotic syndrome (NS) with normal renal function during follow-up. There was a total of 27 patients with TRIM8-related NRS have been identified to date. The most common clinical features are renal diseases (89%), DD (89%), followed by epilepsy (78%). 67% of patients eventually progressed to end-stage renal disease (ESRD). Focal seizure was the most frequent seizure type (57%). 52% of patients presented drug-resistant epilepsy. 64% of patients exhibited non-specific brain MRI abnormalities. Brain atrophy was the most common change (50%). Two patients with TRIM8 variants closer to the N-terminal had neurological diseases without renal damage. Five patients with TRIM8 variants closer to the C-terminal had no severe neurological diseases. Seven patients had Gln459* variant which is the most common variant (7/27, 25.9%). The severity of the renal and neurological damage of the seven patients was variable. This study expands the number of individuals with confirmed NRS due to pathogenic variants in TRIM8. Neurological and renal phenotype with the same variant locus differed in their severity. Further research is needed to explore the relationship between genotype and phenotype of TRIM8 variants.

Prevalence of Early Seizures in Acute Stroke Patients

A stroke is defined as a sudden neurological deficit of cerebrovascular cause that persists beyond 24 hours. Stroke is associated with a whole spectrum of complications, especially post-stroke seizures. These seizures may adversely affect the outcome of stroke in terms of mortality and morbidity. This study was designed to find out the frequency of early post-stroke seizures. Objective: To determine the frequency of early-onset seizures after stroke among patients presenting to tertiary care hospitals. Methods: Two hundred and forty patients, presenting on the Medical floor of Jinnah Hospital Lahore with acute stroke and fulfilling the selection criteria, were approached after informed consent. The patients were followed for 14 days for the development of early seizures after the stroke. Results: Among 240 stroke patients, there were 123 (51.3%) male patients and 117 (48.8%) female patients. The minimum age observed was 30 years and the maximum was noted as 77 years. In 45% of patients, hemorrhagic stroke was detected and 55% of patients had ischemic stroke. From 108 cases of hemorrhagic stroke, there were 10.4% cases in which an episode of seizure occurred within 14 days of stroke. On the other hand, in 132 patients with ischemic stroke, 15.9% of patients developed seizure episodes. Conclusions: It was concluded that ischemic stroke was more common in frequency than hemorrhagic stroke in our population and the occurrence of episode early seizure within 14 days of stroke was more prevalent in ischemic stroke patients.

Application Value of a Machine Learning Model in Predicting Mild Depression Associated with Migraine without Aura.

Aims/Background To investigate the application value of a machine learning model in predicting mild depression associated with migraine without aura (MwoA). Methods 178 patients with MwoA admitted to the Department of Neurology of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from March 2022 to March 2024 were selected as subjects. According to their inpatient medical records, 38 patients were selected as the validation group by random number method, and the remaining 140 patients were included in the modelling group. According to the diagnosis results, the patients in the modelling group and validation group were further divided into a MwoA with mild depression group and a MwoA without mild depression group. Results The results of univariate analysis and Multivariate logistic regression analysis showed that gender, course of disease, attack frequency, headache duration, Migraine Disability Assessment Questionnaire (MIDAS), and Headache Impact Test-6 (HIT-6) score were independent influencing factors for mild depression in MwoA patients (p < 0.05). The receiver operating characteristic (ROC) analysis results showed that the area under the curve of the established prediction model for MwoA patients with mild depression in the modelling group and the validation group was 0.982 and 0.901, respectively, the sensitivity was 0.978 and 0.857, respectively, and the specificity was 0.892 and 0.929, respectively. Conclusion Gender, course of disease, seizure frequency, headache duration, MIDAS score, and HIT-6 score are independent influencing factors for mild depression in patients with MwoA. The model displays good performance for the prediction of mild depression in patients with MwoA.

The correlation of GluR3B antibody with T lymphocyte subsets and inflammatory factors and their role in the progression of epilepsy

ObjectiveTo investigate changes in proportions of peripheral blood lymphocyte subsets, the correlation between the lymphocyte subsets and cytokine levels in patients with GluR3B antibody-positive epilepsy, analyze the role of GluR3B antibodies and cytokines in the progression of epilepsy. In addition, the immunotherapeutic effect in patients with GluR3B antibody-positive epilepsy will be evaluated.MethodsPatients with epilepsy hospitalized in the Department of Neurology of the affiliated Hospital of Xuzhou Medical University from December 2016 to May 2023 were recruited. GluR3B antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Lymphocyte subset proportions were determined using flow cytometry, and serum concentrations of 12 cytokines were measured using cytometric beads array. Differences in T lymphocyte subsets and inflammatory factors were analysed between GluR3B antibody positive and negative patients. Structural equation modeling (SEM) was used to analyse the role of GluR3B antibodies and inflammatory factors in drug-resistant epilepsy (DRE). Finally, the therapeutic effect of immunotherapy on epilepsy patients with GluR3B antibodies was assessed.ResultsIn this study, sixty-four cases of DRE, sixty-six cases of drug-naïve epilepsy (DNE), and forty-one cases of drug-responsive epilepsy were recruited. (1) DRE patients with positive GluR3B antibody were characterized by a significant increase in the proportion of cluster of differentiation (CD)4+ T lymphocytes, a decrease in CD8+ T lymphocytes, and an increase of CD4+/CD8+ ratio. Similar alterations in T lymphocyte subsets were observed in GluR3B antibody-positive patients with DNE. GluR3B antibody levels correlated positively with CD4+ T lymphocytes (r = 0.23) and negatively with CD8+ T lymphocytes (r=-0.18). (2) In patients with DRE, the serum concentrations of interleukin-1β (IL-1β), IL-8, and interferon-gamma (IFN-γ) were significantly higher in those with positive GluR3B antibody compared to those with negative GluR3B antibody. Serum IL-1β levels were also higher in GluR3B antibody-positive DNE patients compared to antibody-negative DNE patients. In drug-responsive epilepsy patients with GluR3B antibody-positive, both serum IL-1β and IFN-γ levels were higher than those with GluR3B antibody-negative. Moreover, the concentrations of serum GluR3B antibody were positively correlated with the levels of IL-1β, IL-8, and IFN-γ. (3) SEM analysis indicated that GluR3B antibody may be a direct risk factor for DRE (direct effect = 4.479, 95%CI 0.409–8.503), or may be involved in DRE progression through affecting IFN-γ and IL-8 levels (total indirect effect = 5.101, 95%CI 1.756–8.818). (4) Immunotherapy significantly decreased seizure frequency and serum GluR3B antibody levels, and the seizure frequency was positively correlated with the levels of GluR3B antibody levels in patients receiving immunotherapy.ConclusionsThis study demonstrates that GluR3B antibody may influence the progression of epilepsy through altering the proportion of CD4+ and CD8+ lymphocyte subsets and increasing proinflammatory cytokines. The seizure suppression of immunotherapy is associated with the decrease of GluR3B antibody levels. Thus, the present study contributes to a better understanding of the immunoregulatory mechanisms of autoimmune-associated epilepsy and provides a potential target for DRE.

Cenobamate's Efficacy for Seizure Treatment in Tuberous Sclerosis Complex

BackgroundEpilepsy is prevalent, and seizure control is challenging in patients with tuberous sclerosis complex (TSC). Cenobamate (CBM) has proven efficacy in several studies; however, its benefit in the TSC population is not known. MethodsWe performed a retrospective review of patients with TSC who received adjunctive CBM for seizure treatments. We assessed treatment efficacy by comparing seizure frequencies three months before CBM (baseline) and those at 3-, 6-, 12-, and 18- month follow-ups. ResultsWe identified 70 patients with TSC receiving CBM and excluded 16 with insufficient data. Fifty-four patients aged 2 to 39 years, with an average baseline seizure of 66.1 ± 88.9 per month, were analyzed. Treatment retention rates at 3, 6, 12, and 18 months were 94.4%, 79.6%, 66.7%, 44.4%, and responder rates (proportions of patients who remained on treatment and had ≥50% seizure reduction) were 38.1%, 51.7%, 53.1%, and 59.1%, respectively. Seizure-free rates at these respective follow-ups were 7.1%, 13.8%, 6.3%, and 9.1%. For patients experiencing reduced seizures, the mean percentage of change ranged from 61.5% to 74.6%. Side effects were common (64.8%), particularly sedation (42.6%), behavioral disturbance (24.1%), and gastrointestinal disturbance (22.2%). ConclusionsMost patients in this study showed seizure reduction; however, the overall responder and seizure-free rates were lower than the literature, likely due to the unique underlying epileptogenesis in TSC and the challenges of tolerating CBM. The lower treatment retention rates signal areas for improvement in concurrent medication adjustment practices.

A comprehensive review on analytical validation methods of cenobamate and upadacitinib

A new antiepileptic medication called cenobamate was just licenced to treat adult partial-onset seizures. By specifically focusing on the persistent sodium current, its special method of action lowers neuronal excitability and the spread of seizures. Cenobamate has been shown to be safe and effective in clinical trials, resulting in notable decreases in the frequency of seizures and enhancements in the patient's quality of life. Patients with uncontrollably occurring seizures may find it to be a desirable option due to its excellent pharmacokinetic profile and few medication interactions. This study examines the possible advantages and disadvantages of cenobamate use in the treatment of epilepsy and summarises the available data in favour of it. A Janus kinase (JAK) inhibitor called The medication upadacitinib is authorised Regarding the management of moderate- to-severe adult inflammatory arthritis (RA). Upadacitinib reduces inflammation and joint injury by inhibiting pro-inflammatory cytokine signalling by blocking JAK enzymes. Its side effects are tolerable and its safety profile is typically acceptable. This review looks at the data that is currently available to support the use of Upadacitinib in the therapy of RA, emphasising its safety, effectiveness, and potential as a treatment alternative for patients who don't respond well to traditional medications.

Neural dynamics and seizure correlations: Insights from neural mass models in a Tetanus Toxin rat model of epilepsy

This study focuses on the use of a neural mass model to investigate potential relationships between functional connectivity and seizure frequency in epilepsy. We fitted a three-layer neural mass model of a cortical column to intracranial EEG (iEEG) data from a Tetanus Toxin rat model of epilepsy, which also included responses to periodic electrical stimulation. Our results show that some of the connectivity weights between different neural populations correlate significantly with the number of seizures each day, offering valuable insights into the dynamics of neural circuits during epileptogenesis. We also simulated single-pulse electrical stimulation of the neuronal populations to observe their responses after the connectivity weights were optimized to fit background (non-seizure) EEG data. The recovery time, defined as the time from stimulation until the membrane potential returns to baseline, was measured as a representation of the critical slowing down phenomenon observed in nonlinear systems operating near a bifurcation boundary. The results revealed that recovery times in the responses of the computational model fitted to the EEG data were longer during 5 min periods preceding seizures compared to 1 hr before seizures in four out of six rats. Analysis of the iEEG recorded in response to electrical stimulation revealed results similar to the computational model in four out of six rats. This study supports the potential use of this computational model as a model-based biomarker for seizure prediction when direct electrical stimulation to the brain is not feasible.

Advancing Pediatric Epilepsy Care: Efficacy and Mechanisms of Melatonin Intervention

Seizures and epilepsies pose significant challenges in pediatric populations, necessitating precise classification and effective management. The International League Against Epilepsy updated its classification system in 2017 to standardize epilepsy care. This study investigated melatonin, a neurohormone known for its role in circadian rhythm regulation, and its potential to enhance the diagnosis, management, and quality of life of pediatric epilepsy patients. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted to explore the relationship between melatonin and pediatric epilepsies. PubMed searches were performed using specific search terms, with eligibility criteria including studies on melatonin’s pathophysiological, biochemical, and therapeutic effects in pediatric epilepsy. Studies involving patients aged 0-18 years were published between 2003 and 2023. Four-teen studies with 898 pediatric patients were included. Melatonin was administered as an adjunct to antiepileptic therapy with the aim of alleviating disorders associated with epileptic encephalopathies or assisting electroencephalogram procedures. Findings were varied: Some studies indicated a reduction in seizure frequency with melatonin, while others provided inconclusive results. Improvements in sleep disorders related to epilepsy were noted with melatonin supplementation, which indirectly enhanced the overall quality of life. Melatonin has potential as an adjunctive therapy for pediatric epilepsy, with positive effects on seizure frequency and sleep quality. However, methodological limitations in some studies and inconclusive data underscore the need for further research to determine the efficacy of melatonin in pediatric epilepsy management. The diverse potential of melatonin in treating neurological disorders highlights the importance of continued, comprehensive research into its therapeutic application.

Total posterior quadrant disconnection for drug‐resistant epilepsy in children

AbstractObjectiveTo assess seizure outcomes, prognostic factors, and developmental changes in children undergoing total posterior quadrant disconnection (PQD) for drug‐resistant epilepsy (DRE).MethodsWe conducted a retrospective analysis of the clinical data of children with DRE who underwent total PQD surgery. The study focused on Engel's classification for seizure outcomes, exploring correlation of preoperative data and surgical effectiveness, and predictors of seizure prognosis. It involved a comparative analysis of developmental levels pre‐ and 3 months postoperatively using Griffiths Mental Development Scales‐China (GMDS‐C), and the correlation between clinical characteristics and GMDS‐C results.ResultsOut of 61 pediatric patients, 70.5% showed no seizure recurrence postoperatively. In the univariate analysis, interictal electroencephalogram (EEG), magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG‐PET), and acute postoperative seizure (APOS) were significantly related to surgical prognosis. In multivariate analysis, interictal EEG and APOS were identified as predictors of seizure prognosis. Survival analysis indicated significant associations between MRI, interictal EEG, FDG‐PET, APOS and postoperative seizure occurrence. Preoperative GMDS‐C levels were significantly correlated with epilepsy duration, seizure frequency, interictal EEG, and FDG‐PET. GMDS‐C scores improved postoperatively, while developmental quotients remained stable.SignificanceFor patients with structural abnormalities in the entire posterior quadrant, thorough preoperative assessment and timely total PQD surgery can effectively control seizures without causing neurological development deterioration. APOS and interictal EEG abnormalities beyond the posterior quadrant are predictors for seizure prognosis but should not be deemed contraindications for surgery.Plain Language SummaryDue to lack of analysis on pediatric total PQD cases, 61 pediatric patients who underwent total PQD surgery were retrospectively enrolled. Seizure and development results were collected and analyzed as dependent variables. The study found that 70.5% of patients were seizure‐free and showed development improvement, with no deaths or severe complications reported. Prognosis predictors included APOS and interictal EEG abnormalities beyond the posterior quadrant.

Deciphering Developmental Epileptic Encephalopathies (DEE): Unravelling the Key Signs

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Epilepsy, a chronic neurological disorder affecting over 50 million people worldwide, is marked by recurrent seizures and loss of consciousness. It is categorized based on EEG features, etiologies, and comorbidities. Developmental Encephalopathy (DE) involves developmental delays and early-onset seizures without causing developmental regression. In contrast, Epileptic Encephalopathy (EE) features severe epilepsy syndromes where frequent seizures result in developmental delays or regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This review explores the clinical definitions, epidemiology, and diagnostic criteria for DE, EE, and DEEs. It covers their etiologies, clinical features, diagnostic methods, and treatment strategies, including genetic, structural, metabolic, and immune-related factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; DE features developmental impairment with epilepsy, while EE involves severe epilepsy causing cognitive and behavioral dysfunction. DEEs are marked by early-onset severe epilepsy and EEG abnormalities that worsen developmental impairments. Essential diagnostic tools include EEG, neuroimaging, and genetic testing. Effective management requires personalized interventions to control seizures and address cognitive deficits.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; DEEs are a complex epilepsy subset with major developmental and cognitive challenges. Early diagnosis and targeted treatments are crucial for improving outcomes. Ongoing research into DEEs' genetic and pathophysiological mechanisms is key to enhancing understanding and management.&lt;/p&gt;

Systematic literature review of the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures in adults.

This systematic literature review (SLR) assessed the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures (PGTCS) in adults to evaluate these domains in both populations and identify evidence gaps to inform future research. A search was conducted on December 7, 2022, using MEDLINE and Embase to identify studies published from 2012 onwards reporting humanistic burden (patient-reported or caregiver-reported outcomes or utilities, qualitative evaluations), economic burden (productivity loss, caregiver and societal costs of epilepsy), and sleep-related outcomes. Of the 2830 citations identified, 136 were included. Most studies were in the focal epilepsy population; very few studies reported outcomes in the PGTCS population. The presence of epilepsy-specific instruments varied based on the domain evaluated. Epilepsy exerted considerable humanistic and economic burden. Indicators of poor disease control (e.g., high seizure frequency, resistance to anti-seizure medications, polypharmacy) increased epilepsy burden. Seizure frequency and type, disease severity, and polypharmacy also affected work productivity. Adults with epilepsy, particularly focal epilepsy, reported higher indirect costs, more sick days accrued, and early entry into retirement. Caregivers similarly reported high productivity loss and absenteeism related to caregiving duties. The results of this SLR highlight the high humanistic and economic burden of focal epilepsy and PGTCS, although limited data were available for the PGTCS population. The results include patient-reported outcome data specific to focal epilepsy and PGTCS, expanding the limited humanistic burden evidence identified in previous reviews, and show the effect of poor disease control on individuals' lives and as a driver of indirect costs. PLAIN LANGUAGE SUMMARY: Our systematic literature review identified studies that evaluated the impact of focal epilepsy and primary generalized tonic-clonic seizures on patients and their caregivers. We found that focal epilepsy negatively impacted patients' mental health and sleep and was associated with higher indirect costs and lower work productivity in people with more severe disease. The impact of primary generalized tonic-clonic seizures on patients was rarely reported, and future research is needed.

Clinical efficacy and safety of perampanel monotherapy as primary anti-seizure medication in the treatment of pediatric epilepsy: A single-center, prospective, observational study.

To assess the efficacy and safety of perampanel (PER) as primary monotherapy in patients aged 4-18 years old with epilepsy. A single-center, prospective, observational study was conducted from October 2021 to October 2023, to evaluate PER monotherapy's efficacy and safety as initial therapy for pediatric epilepsy. Changes in seizure frequency, safety, and retention rate were observed at 3, 6, 9, and 12 months after initiating PER primary monotherapy. A total of 124 children aged 4-15 years (mean age = 8.25 ± 2.50 years) were included in the Analysis Sets. The retention rates at 3, 6, 9, and 12 months were 88.71% (110/124), 84.68% (105/124), 78.26% (90/115), and 71.58% (68/95), respectively. Seizure freedom rates at 3, 6, 9, and 12 months were 85.45%, 79.09%, 76.24%, and 75.31%, respectively. The responder rates (≥50% but <100%) at the same endpoints were 9.09%, 14.55%, 12.87%, and 7.41%, respectively. Seizure freedom rate of PER was independent of age at PER initiation, seizure onset age, gender, baseline frequency, seizure types, and family history of epilepsy (p > 0.05) but associated with duration of treatment (p = 0.001) and maintenance dose (p = 0.022). Additionally, 124 patients were included in the safety analysis set. The overall adverse event rate was 38.71% (48/124), with irritability (19 cases, 15.32%) and dizziness (18 cases, 14.52%) being the most common adverse effects. One patient discontinued PER monotherapy within 1 month due to unbearable itching of the skin. PER monotherapy as the primary anti-seizure medication (ASM) for pediatric epilepsy demonstrates high efficacy and safety in real-world clinical treatment. Patients who respond well to this drug and adhere to long-term treatment can achieve favorable seizure control. Furthermore, patients achieving seizure freedom with a relatively lower dose can opt for the same dose as the maintenance dose. This study provided the efficacy and safety of PER monotherapy as the primary ASM for Chinese pediatric epilepsy. In total, 124 patients took part. The seizure freedom rates were over 70% at different observation points (OPs), along with a retention rate of 71.58% at the 12-month OP. Most of adverse effects observed were mild to moderate.

Effects of antiseizure medication withdrawal during the first trimester of pregnancy on seizure control and offspring outcomes.

To explore seizure control and offspring outcomes associated with antiseizure medication (ASM) withdrawal during the first trimester of pregnancy. Based on a prospective multicenter study in China, pregnancies followed up between 2009 and 2023 at the neurology outpatient clinic of 50 hospitals were included in this study. Information on demographics, epileptic characteristics, treatment during pregnancy, and offspring outcomes was collected. Pregnancies were categorized into an ASM withdrawal group and an ASM continuation group. Balance tests and univariate log-binomial regression analysis were conducted to identify imbalanced factors between groups and potential risk factors for seizure deterioration during pregnancy. Multivariate log-binomial regression was then used to estimate the adjusted effects of ASM withdrawal on seizure deterioration during pregnancy and fetal outcomes. In addition, exploratory subgroup analysis was conducted to identify high-risk patients who should avoid ASM withdrawal. Of the 695 pregnancies enrolled, 14.2% withdrew ASMs in the first trimester of pregnancy. ASM withdrawal during this period was associated with a risk of seizure deterioration during pregnancy (adjusted risk ratio [aRR] 1.405, 95% confidence interval [CI] 1.009-1.876). Subgroup analysis revealed a significant risk of seizure deterioration in pregnancies with seizures in 9 months (aRR 1.590, 95% CI 1.079-2.344). After adjusting the folic acid dose, no evidence of protective effects on fetus after ASM withdrawal was observed compared to patients with continued treatment, whereas seizure deterioration during pregnancy increased the risk of fetal death (aRR 3.577, 95% CI 1.086-11.651). ASM withdrawal in the first trimester of pregnancy did not show a protective effect on fetal outcomes but rather resulted in increased seizure frequency during pregnancy. However, this finding requires a larger sample for validation. Furthermore, seizure deterioration during pregnancy was associated with an increased risk of fetal death.

A novel AAV9-dual microRNA-vector targeting GRIK2 in the hippocampus as a treatment for mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (mTLE) is the most prevalent type of epilepsy in adults. First and subsequent generations of anti-epileptic therapy regimens fail to decrease seizures in a large number of patients suffering from mTLE, leaving surgical ablation of part of the hippocampus as the only therapeutic option to potentially reach seizure freedom. GluK2 has recently been identified as a promising target for the treatment of mTLE using gene therapy. Here, we engineered an adeno-associated virus serotype 9 vector expressing a cluster of two synthetic microRNAs (miRNAs), expressed from the human synapsin promoter, that target GRIK2 mRNA. Intra-hippocampal delivery of this vector in a mouse model of mTLE significantly reduced GRIK2 expression and daily seizure frequency. This treatment also improved the animals' health, reduced their anxiety, and restored working memory. Focal administration of the vector to the hippocampus of cynomolgus monkeys in GLP toxicology studies led to the selective transduction of hippocampal neurons with little exposure elsewhere in the brain and no transduction outside the central nervous system. Expression of miRNAs in hippocampal neurons resulted in substantially decreased GRIK2 mRNA expression. These data suggest that the intra-hippocampal delivery of a GMP-grade AAV9 coding for a synthetic miRNAs targeting GRIK2 is a promising treatment strategy for mTLE.

Centromedian thalamic deep brain stimulation for idiopathic generalized epilepsy: Connectivity and target optimization.

There are limited treatment options for individuals with drug-resistant idiopathic generalized epilepsy (IGE). Small, limited case series suggest that centromedian thalamus deep brain stimulation (CM-DBS) may be an effective treatment option. The optimal CM-DBS target for IGE is underexamined. Here, we present a retrospective analysis of CM-DBS targeting and efficacy for five patients with drug-resistant IGE. Volume of tissue activated (VTA) overlap with CM nucleus was performed using an open-source toolbox. Median follow-up time was 13 months. Median convulsive seizure frequency reduction was 66%. One patient had only absence seizures, with >99% reduction in absence seizure frequency. Four patients had electrode contacts positioned within the CM nucleus target, all of whom had >50% reduction in primary semiology seizure, with 85% median seizure reduction (p = .004, paired-sample t test). Volumetric "sweet-spot" mapping revealed that best outcomes were correlated with stimulation of the middle ventral CM nucleus. Connectivity strength between the sweet-spot region and central peri-Rolandic cortex was increased significantly relative to other cortical regions (p = 8.6 × 10-4, Mann-Whitney U test). Our findings indicate that CM-DBS can be an effective treatment for patients with IGE, highlight the importance of accurate targeting and targeting analysis, and within the context of prior work, suggest that ideal CM-DBS targets may be syndrome specific.

Romanian Translation and Cultural Adaptation of the Seizure Severity Questionnaire.

Four translators were involved in obtaining conceptual analogies and the cultural importance of the translated notions. The final version was obtained for the Romanian population, with the same appearance as the original instrument. Sixty-seven patients with epilepsy completed the SSQ and the Patient-Weighted Quality of Life in Epilepsy Inventory-QOLIE-31-P. Females had a lower mean SSQ total score (TS) and perceived seizures less seriously than men. Patients with epilepsy with aura had a higher mean SSQ TS, with a more severe seizure perception, compared to those without aura. According to the frequency of seizures, patients with epilepsy with rare seizures had the lowest mean SSQ total score (TS) compared to those with frequent seizures. Patients who were on monotherapy had a less severe perception of epileptic seizures compared to those who were treated with two or more antiepileptic drugs. All QOLIE-31-P domains and TS correlated statistically significantly with the SSQ TS. This study explored SSQ translation, evaluated preliminary results, and showed the correlation between seizure frequency and severity, clinical factors, and quality of life. This tool could be useful for measuring seizure severity in Romanian patients with epilepsy and conducting comparative studies.