Outcome Of Epilepsy Research Articles

Role of specific interictal and ictal EEG onset patterns.

The objective of this review is to present the role of specific interictal and ictal EEG onset patterns during scalp video-EEG monitoring. Specific non-epileptiform abnormalities include temporal intermittent rhythmic delta activity (TIRDA) and temporal intermittent rhythmic theta activity (TIRTA) indicating a temporal lobe seizure onset, while interictal rhythmical midline theta activity occurs more frequently in frontal epilepsy. Specific interictal epileptiform abnormalities comprise Type 1 spikes pointing towards a mesial and Type 2spikes indicating a lateral temporal irritative zone. Unilateral temporal interictal epileptiform discharges (IEDs) are predictive for a good surgical seizure outcome in temporal lobe epilepsy. Small sharp spikes (SSS) named Benign Epileptiform Transients of Sleep (BETS) in the past represent scalp EEG markers of hippocampal epileptic activity. While the localizing value of IEDs in extratemporal epilepsies is often limited, a consistently localized spike focus predicts a good surgical seizure outcome in non-lesional extratemporal patients. A specific ictal EEG pattern for mesial temporal lobe epilepsy consists of a 5-9Hz rhythmic temporal activity which also predicts a good surgical outcome. In extratemporal epilepsies, ictal scalp EEG frequently is non-localized. Concerning the correspondence of ictal scalp-EEG and intracranial EEG (iEEG) patterns there is no simple one-to-one relationship. Scalp-EEG and iEEG patterns correspond closer to each other when there is no delay between clinical and scalp-EEG onset. Paroxysmal fast activity on scalp-EEG matches with low-voltage fast activity on iEEG. Repetitive epileptiform discharges on scalp EEG indicate an underlying focal cortical dysplasia.

Secular trends of the incidence of encephalitis and outcomes of postencephalitic epilepsy in Taiwan: A nationwide population-based study.

Encephalitis can lead to significant disability among survivors. Up-to-date estimates of encephalitis incidence and the risk of postencephalitic epilepsy (PE) are crucial for informing health policy. We used the National Taiwan Insurance Research Database to estimate the standardized incidence of encephalitis for each year from 2003 to 2017. We analyzed PE among these cases. From 2003 to 2017, the age- and sex-standardized incidence of encephalitis increased from 5.95 (95% confidence interval [CI]: 5.61-6.28) to 10.46 (95% CI: 10.04-10.87) per 100,000 person-years, with an annual percentage change of 1.6% (1.1-2.2, p < 0.05). However, yearly variation was observed. The incidence was consistently higher in patients under 18 years than in those aged ≥ 18 years throughout the study period. In 2017, the highest annual incidence was seen in adults aged ≥ 70 years and in children aged 1-4 years. Approximately 20% of the survivors developed PE within 5 years, with the highest risk observed in infants under 1 year of age. The overall incidence of encephalitis in Taiwan increased from 2003 to 2017. Pediatric patients, particularly those under 1 year of age, are more vulnerable to encephalitis and its long-term complications, including PE, compared to adults, except for those aged ≥ 70 years.

The association of polytherapy and psychiatric comorbidity in epilepsy.

Managing epilepsy may require using more than one anti-seizure medication (ASM). While combination therapy may help, risks, including psychiatric problems, are not fully explored in Africa. We examined the relationship between polytherapy and psychiatric comorbidities among attendees of an epilepsy community clinic. We prospectively assessed individuals attending an outpatient clinic in Kilifi, Kenya, for patterns of ASM prescribing (mono- or polytherapy) and reviewed psychiatric diagnoses. We used the Psychosis Screening Questionnaire and the Patient Health Questionnaire Version 9 to assess for psychosis and depression, and the Child Behavior Checklist to assess for emotional and behavioural problems. We conducted a cross-sectional logistic regression analysis to determine factors associated with polytherapy and examine the impact of polytherapy and specific medication on psychiatric comorbidities. Of 3,016 attendees, most were on older ASM (99.7%), with about a third (32.9%) on polytherapy. The most commonly co-administered drugs were phenobarbital and carbamazepine (13.0%). Children were less likely to be on multiple medications than adults, and there was no difference between the sexes. Polytherapy was associated with focal to bilateralised seizures (aOR 1.2 [95% confidence interval:1.0-1.4]) and frequent seizures (aOR=2.1 [1.5-2.9]). Combining drugs increased the likelihood of any psychiatric problems (aOR=1.3 [1.0-1.8]), with polytherapy associated with depression (aOR=2.9 [1.0-8.4]) and psychosis (aOR=1.9 (1.0-3.6)). Polytherapy, especially with older drugs, is associated with psychiatric comorbidities in this population. Resorting to polytherapy needs to be carefully considered. Prioritizing research into the long-term effects of ASM on psychiatric comorbidities is crucial for improving mental health outcomes in epilepsy, particularly in low-income settings.

Maternal epilepsy and pregnancy, delivery and neonatal outcomes: A population-based retrospective cohort study.

To investigate associations between maternal epilepsy and pregnancy, delivery and neonatal outcomes. A population-based retrospective cohort study was conducted using the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) database, between 2004-2014. Through logistic regression analysis, we compared associations between epilepsy and pregnancy-related outcomes while adjusting for demographic characteristics and comorbidities. Of 9,096,788 pregnancies, 25,044 were in pregnant women with epilepsy (PWWE). PWWE were more likely to be younger, white or black, have a lower income and to be insured through Medicare or Medicaid. Furthermore, PWWE were more likely to have been diagnosed with obesity, chronic hypertension, gestational diabetes, thyroid disease and HIV, and to have smoked tobacco during pregnancy or used illicit drugs. Pregnancy and delivery outcomes associated with epilepsy include pregnancy-induced hypertension(adjusted OR(aOR):1.26, 95%CI:1.21-1.32), preeclampsia(aOR:1.33, 95%CI:1.26-1.41), eclampsia(aOR:8.34, 95%CI:7.14-9.74), superimposed preeclampsia/eclampsia(aOR:1.29, 95%CI:1.14-1.47), placenta previa(aOR:1.24, 95%CI:1.06-1.44), preterm delivery(aOR:1.27, 95%CI:1.21-1.32), abruptio placenta(aOR:1.24, 95%CI:1.12-1.36), chorioamnionitis(aOR:1.12, 95%CI:1.02-1.23), cesarean section(aOR:1.29, 95%CI:1.25-1.33), hysterectomy(aOR:1.79, 95%CI:1.31-2.45), postpartum hemorrhage(aOR:1.12, 95%CI:1.05-1.21), wound complications(aOR:1.38, 95%CI:1.17-1.63), maternal death(aOR:3.42, 95%CI:1.79-6.53), transfusion(aOR:1.67, 95%CI:1.53-1.83), maternal infection(aOR:1.18, 95% CI:1.09-1.28, p<0.001), deep vein thrombosis(aOR:2.11, 95%CI:1.43-3.10), pulmonary embolism(aOR:2.98, 95%CI:1.87-4.76), venous thromboembolism(aOR:2.25, 95%CI:1.65-3.08) and disseminated intravascular coagulation(aOR:1.48, 95%CI:1.19-1.83). Epilepsy-linked neonatal complications include small for gestational age(aOR:1.52, 95%CI:1.43-1.62), intrauterine fetal demise(aOR:1.20, 95%CI:1.02-1.41) and congenital anomalies(aOR:2.76, 95%CI:2.47-3.07). PWWE have significantly higher risk of nearly every pregnancy, delivery and neonatal complication investigated, including maternal death and intrauterine fetal demise. PWWE should be considered high risk patients and be carefully followed during pregnancy.

Early life stress influences epilepsy outcomes in mice.

Stress is a common seizure trigger that has been implicated in worsening epilepsy outcomes, which encompasses psychiatric and cognitive comorbidities and sudden unexpected death in epilepsy (SUDEP) risk. The neuroendocrine response to stress is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and HPA axis dysfunction worsens epilepsy outcomes, increasing seizure burden, behavioral comorbidities, and risk for SUDEP in mice. Early life stress (ELS) reprograms the HPA axis into adulthood, impacting both the basal and stress-induced activity. Thus, we propose that ELS may influence epilepsy outcomes by influencing the function of the HPA axis. To test this hypothesis, we utilized the maternal separation paradigm and examined the impact on seizure susceptibility. We show that ELS exerts a sex dependent effect on seizure susceptibility in response to acute administration of the chemoconvulsant, kainic acid, which is associated with an altered relationship between seizure activity and HPA axis function. To further examine the impact of ELS on epilepsy outcomes, we utilized the intrahippocampal kainic acid model of chronic epilepsy in mice previously exposed to maternal separation. We find that the relationship between corticosterone levels and the extent of epileptiform activity is altered in mice subjected to ELS. We demonstrate that ELS impacts behavioral outcomes associated with chronic epilepsy in a sex-dependent manner, with females being more affected. We also observe reduced mortality (presumed SUDEP) in female mice subjected to ELS, consistent with previous findings suggesting a role for HPA axis dysfunction in SUDEP risk. These data demonstrate for the first time that ELS influences epilepsy outcomes and suggest that previous life experiences may impact the trajectory of epilepsy.

Therapeutic yield of comprehensive inpatient treatment for patients with intellectual disability and epilepsy - A prospective observational study.

In people with intellectual disability (ID), prevalence of epilepsy can be over 40-times higher than in normally intelligent people, impacting quality of life (QoL) of those affected. Patients with ID are often excluded from clinical trials, resulting in limited evidence regarding treatment. This study aimed to evaluate effects of a comprehensive inpatient treatment program on seizure outcome and QoL and to identify predictive factors for improvement in these measures. This prospective observational study included people with epilepsy (PWE) and ID (IQ < 70) who underwent comprehensive inpatient treatment in a tertiary epilepsy center. The program consisted of adjustments of anti-seizure medication (ASM) and various interventions such as occupational therapy, ergotherapy, logopedics, physiotherapy and counseling services, requiring a minimum hospital stay of 14days. Outcome was measured by the Liverpool Seizure Severity Scale (LSSS), Glasgow Epilepsy Outcome Scale (GEOS), Aberrant Behavior Checklist (ABC), and Liverpool Adverse Events Profile (LAEP), alongside global QoL (numerical rating scale; 10 best, 0 worst) by caregivers. Seizure outcome was classified as "favorable" for patients experiencing not more than one seizure per month without any seizure-related injuries in the last 2months. Data were collected within 2weeks prior to admission and 8weeks post-discharge. Wilcoxon signed rank tests and regression analysis were used to assess the effects of inpatient treatment and to identify predictive factors. A total of 65 patients (30 female, median age 32years) were included. During their hospital stays, number of ASM was reduced significantly, but not the total ASM dosage. Inpatient treatment led to a significant improvement in favorable seizure outcome (25% before admission vs. 46% after discharge; p=0.004) and ASM adverse effects (LAEP median 34.0 vs. 31.0; p=0.006). QoL ratings improved significantly post-treatment (rating scale median 4.0 vs. 6.0; p=0.0015). A significant improvement of global QoL after discharge compared to the time point before admission was independently associated with a reduction of ASM number during hospital stay (p=0.011). In general, higher global QoL after discharge was independently associated with a favorable seizure outcome (p<0.001) and lower scores for ASM adverse effects (p=0.03). In PWE and ID, a comprehensive inpatient treatment program may be helpful to reduce burden of seizures and of ASM adverse effects as well as to improve global QoL. A reduction of the number of ASM may facilitate improvement of global QoL.

Clinical features and outcomes of late-onset epilepsy of unknown etiology: A retrospective study in West China.

Late-onset epilepsy (LOE) usually refers to the development of epilepsy at the age of 50years or older. Approximately 20% of LOE cases are diagnosed as late-onset epilepsy of unknown etiology (LOUE) due to a lack of an identifiable cause. The aim of this study was to investigate the clinical features, seizure and cognitive outcomes of patients with LOUE in West China. Patients diagnosed with LOUE at West China Hospital between January 2015 and December 2022 were retrospectively recruited. The seizure and cognitive outcome were followed up for at least 1year after discharge. Logistic regression models were applied to investigate the risk factors of recurrent seizure and cognitive impairment in patients with LOUE. We included 286 LOUE patients with a median seizure onset age of 59years. The most common seizure types were focal to bilateral tonic-clonic seizure (61.9%) and focal non-motor seizure (37.0%). Two-hundred and seventy-seven (96.9%) patients underwent video electroencephalography (VEEG), with seizures recorded in 11.9% of patients and interictal epileptiform discharges in 58.2% cases. Majority of the patients (73.4%) received monotherapy, with levetiracetam, oxcarbazepine and valproate being the most commonly prescribed anti-seizure medications. During the follow-up, 69.1% of patients achieved seizure-free. Multivariate analysis identified ictal event recorded during VEEG monitoring (OR:0.205, 95% CI: 0.045-0.932, p=0.040) and memory impairment (OR:2. 470, 95% CI: 1.181-5.167, p=0.016) as significant factors associated with recurrent seizure. Twenty-two patients were classified as cognitive impairment. The onset age (OR:1.095, 95% CI:1.032-1.162, p=0.003) and total Fazekas score (OR=6.770, 95% CI:1.972-23.241, p=0.002) were significant risk factors associated with cognitive dysfunction. LOUE is generally a benign form of epilepsy with a high percentage of patients achieving seizure-free status. However, these patients are at a higher risk of memory decline and cognitive dysfunction.

Introducing the Index of Response to Stimulation (IRES): A Novel Metric for Assessing Vagus Nerve Stimulation Outcomes in Drug-Resistant Epilepsy.

Background and Objectives: The Index of Response to Stimulation (IRES) is a new index that we introduce in this study to grade the effectiveness of vagus nerve stimulation in the treatment of drug-resistant epilepsy. We assessed 76 patients at 6, 12, and 18 months after VNS evaluating improvement with the IRES in four key dimensions: seizure duration decrease, seizure intensity decrease, improvement in quality of life, and seizure frequency decrease. This scale goes from 0, meaning no improvement, to 8, meaning maximal improvement, making the scale a really good measure of clinical utility. Materials and Methods: This retrospective study followed 76 patients aged 20-65, assessing changes in their IRES scores after VNS therapy using the ASPIRE SR 106 device. Therapy settings were adjusted biweekly to optimize efficacy and patient tolerance. Results: There were improvements in the control of the seizures, measured in terms of increased IRES scores. Improvements were associated with quality-of-life enhancements for the patient and a lesser frequency and intensity of the seizures, testifying further to the predictive ability of the IRES toward successful outcomes. This fact reveals that epilepsy treatment must be individual, according to the profile of the patient. Conclusions: The study confirms the IRES to be a valid tool for the assessment of the impact of VNS on drug-resistant epilepsy and promotes it as an integral part of the evaluation of the patient for personalized therapy. The findings encourage the use of IRES among the elements that support patient selection and insist on its role in the advancement of precision medicine and optimization of treatment.

Gestational Hypertension, Preeclampsia, and Eclampsia and Future Neurological Disorders

Gestational hypertension, preeclampsia, and eclampsia are established risk factors for stroke and dementia later in life. Whether these pregnancy complications are associated with an increased risk of new-onset neurological disorders within months to years after giving birth is not known. To explore whether gestational hypertension, preeclampsia, and eclampsia are associated with new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth. In this register-based cohort study, exposures were identified in the Swedish Medical Birth Register from 2005 to 2018. Follow-up was conducted using the National Patient Register, containing diagnoses from specialized inpatient and outpatient care. Follow-up started 42 days after delivery and continued until the first event, death, emigration, or the end of the follow-up period (2019). The risk was calculated with Cox regression analysis and expressed as adjusted hazard ratio (aHR) with a 95% CI. Through the Swedish Medical Birth Register, 659 188 primiparous women with singleton pregnancies between 2005 and 2018 were identified. Women with a diagnosis of chronic hypertension (n = 4271) or a prepregnancy neurological disorder (n = 6532) were excluded. The final study population included 648 385 women. Data analyses were conducted in 2023. Gestational hypertension, preeclampsia, and eclampsia. The primary outcome was a composite neurological outcome of migraine, headache, epilepsy, sleep disorder, or mental fatigue. The study included 648 385 women with a mean age of 28.5 (SD, 5.0) years at the time of their first pregnancy. Women with gestational hypertension (n = 11 133), preeclampsia (n = 26 797), and eclampsia (n = 625) all had an association with increased risk for a new-onset neurological disorder compared with women with normotensive pregnancies. The aHR for gestational hypertension was 1.27 (95% CI, 1.12-1.45), 1.32 (95% CI, 1.22-1.42) for preeclampsia, and 1.70 (95% CI, 1.16-2.50) for eclampsia. When exploring individual outcomes, women with eclampsia were associated with more than a 5 times increased risk of epilepsy (aHR, 5.31; 95% CI, 2.85-9.89). In this study, gestational hypertension, preeclampsia, and eclampsia were associated with an increased risk of new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth. Guidelines recommend follow-up after delivery for women with gestational hypertension and preeclampsia for their increased risk of cardiovascular disease. At these visits, caregivers should also pay attention to persisting or new-onset of neurological symptoms, since this group of women appears to be vulnerable to developing or experiencing neurological disorders.

Progressive brain atrophy and cortical reorganization related to surgery in temporal lobe epilepsy.

Epilepsy is associated with progressive cortical atrophy exceeding normal aging. We aimed to explore longitudinal cortical alterations in patients with temporal lobe epilepsy (TLE) and distinct surgery outcomes. We obtained longitudinal T1-weighted MRI data in a well-designed cohort, including 53 operative TLE patients, 23 nonoperative TLE patients, and 23 healthy controls. According to seizure outcomes at 24 months after surgery, operative patients were divided into seizure-free (SF) and nonseizure-free (NSF) group. Operative patients were scanned before and after surgery, while nonoperative patients and healthy controls were rescanned with similar interval times. We measured gray matter volume (GMV) in all participants and compared longitudinal cortical alterations among groups. In nonoperative group, statistically significant GMV decrease was observed in ipsilateral median cingulate and paracingulate gyri and cerebellum crus I when compared with healthy controls. In operative group, postoperative GMV increase was discovered in many regions involving bilateral hemispheres, especially in the frontal lobe, without differences between SF and NSF group. Postoperative GMV decrease was found in ipsilateral inferior frontal gyrus, putamen, thalamus, and insula. GMV decrease in ipsilateral inferior frontal gyrus, putamen, and insula was more significant in SF group. Progressive cortical atrophy existed in nonoperative TLE patients. Cortical remodeling indicated by postoperative GMV increase may arise mostly from the surgery itself, rather than postsurgical seizure outcomes. More significant GMV decrease in ipsilateral inferior frontal gyrus, putamen, and insula may imply their closer connections with resected regions in seizure-free patients.

Variants in EP400, encoding a chromatin remodeler, cause epilepsy with neurodevelopmental disorders.

EP400 encodes a core catalytic ATPase subunit of ATP-dependent chromatin remodeling complexes. The gene-disease association of EP400 is undetermined. In this study, we performed trio-based whole-exome sequencing in a cohort of 402 families with epilepsy and neurodevelopmental disorders (NDDs) and identified compound heterozygous EP400 variants in six unrelated individuals. Six additional EP400 individuals were recruited via the match platform of China, including two de novo heterozygous and four compound heterozygous variants. The individual with a heterozygous de novo frameshift variant presented with NDDs, while the others exhibited epilepsy and NDDs, explained by the damaged genetic dependence quantity. EP400 presented significantly higher excesses of variants in the individuals. Clustering analysis revealed that the majority paralogs of EP400 were associated with NDDs/epilepsy and co-expressed highly with EP400. Analysis of the spatiotemporal expression indicated that EP400 is highly expressed in the developing brain and cells during differentiation, indicating its vital role in neurodevelopment; EP400 is predominantly expressed in inhibitory neurons in the early stage but in excitatory neurons in the mature stage. The development-dependent expression pattern of neuron specificity explained the favorable outcome of epilepsy. Knockdown of EP400 ortholog in Drosophila caused significantly increased susceptibility to seizures and abnormal neuronal firing. The ep400 crispant zebrafish exhibited brain developmental abnormalities, poorer adaptability, lower response to stimulation, epileptic discharges, abnormal cellular apoptosis, and increased susceptibility to seizures. Transcriptome analysis showed that ep400 deficiency caused expressional dysregulation of 84 epilepsy/NDD-associated genes, including 11 highly dose-sensitive genes. This study identified EP400 as a causative gene of epilepsy/NDDs.

Stereoelectroencephalographic thermocoagulation in FLNA-positive heterotopia: Is it an effective treatment?

Periventricular nodular heterotopia (PVNH) is a neuronal migration disorder often associated with drug-resistant epilepsy. The epileptogenic zone network (EZN) in PVNH is generally large, contraindicating surgery. Stereoelectroencephalography (SEEG) can be proposed to map the EZN and perform radiofrequency thermocoagulation (THC) with an efficacy rate of approximately 65%. There are genetic forms of PVNH, particularly with mutations in the filamin A gene (FLNA). However, data on SEEG-guided THC in these patients still have not been described. We report four patients with FLNA-positive PVNH who underwent SEEG-guided THC. All were women with several types of seizures and psychiatric comorbidities. EZN was extensive and often bilateral, including a part of the heterotopias. The outcomes of SEEG-guided THC varied; two patients experienced significant seizure reduction and improvement in psychiatric symptoms (Engel class I-II), one showed partial improvement (Engel class III), and one had no significant benefit (Engel class IV). Psychiatric comorbidities, including posttraumatic stress disorder, depression, and anxiety, were present in all cases, with some patients showing symptom improvement alongside seizure reduction. Despite genetic origin, SEEG-guided THC can be proposed in FLNA-positive PVNH-related epilepsy, although outcomes vary. The presence of FLNA mutations should not contraindicate surgical intervention but may influence the therapeutic response. Further research is needed to understand the impact of genetic variants on epilepsy outcome.

Causal Brain Network in Clinically-Annotated Epileptogenic Zone Predicts Surgical Outcomes of Drug-Resistant Epilepsy.

Patients with drug-resistant epilepsy (DRE) are commonly treated using neurosurgery, while its success rate is limited with approximately 50%. Predicting surgical outcomes is currently a prominent topic. The DRE is recognized as a network disorder involving a seizure triggering mechanism within epileptogenic zone (EZ); however, a systematic exploration of the EZ causal network remains lacking. This paper will advance DRE study by: (1) developing a novel causal coupling algorithm, "full convergent cross mapping (FCCM)" to improve the quantization performance; (2) characterizing the DRE's multi-frequency epileptogenic network by FCCM calculation of ictal iEEG; (3) predicting surgical outcomes using network features and machine learning. Numerical validations demonstrate the FCCM's superior quantization in terms of nonlinearity, accuracy, and stability. A multicenter cohort containing 22 DRE patients with 81 seizures is included. Based on the Mann-Whitney-U-test, coupling strength of the epileptogenic network in successful surgeries is significantly higher than that of the failed group, with the most significant difference observed in α -iEEG network (p = 1.52e - 07 ) Other clinical covariates are also considered and all th α -iEEG networks demonstrate consistent differences comparing successful and failed groups, with p = 0.014 and 9.23e - 06 for lesional and non-lesional DRE, p = 2.32e - 05, 0.0074 and 0.0030 for three clinical centers CHFU, JHU and NIH. Using FCCM features and 10-fold cross validation, the SVM achieves the highest accuracy of 87.65% in predicting surgical outcomes. The epileptogenic causal network is a reliable biomarker for estimating DRE's surgical outcomes. The proposed approach is promising to facilitate DRE precision medicine.

Epilepsy and nicotine use: Exploring disparities in ENDS and cigarette use among US adults with epilepsy

IntroductionIndividuals with epilepsy are at greater risk for tobacco use, which may exacerbate their health challenges. This study examines the prevalence and sociodemographic correlates of electronic nicotine delivery systems (ENDS), cigarette, and dual use among US adults with and without epilepsy. MethodsData from the 2021–2023 National Health Interview Surveys were analyzed (N = 86,655 adults aged ≥ 18 years), including 1,579 (1.89 %, estimated 14.5 million US adults) with self-reported epilepsy (outcome variable). Participants were categorized into mutually exclusive groups: never-use of either product [reference group], current (used on some days or daily) cigarette-only use, ENDS-only, dual-use, former cigarette-only, former ENDS-only, and former dual-use. Weighted logistic regression models assessed the relationship between epilepsy and tobacco use, adjusting for sociodemographic characteristics. ResultsAdults with epilepsy had higher rates of cigarette-only (16.51 % vs. 9.27 %), ENDS-only (5.56 % vs. 3.95 %), and dual use (3.53 % vs. 1.50 %) compared to those without epilepsy. Relative to never use, current cigarette-only use (AOR = 1.66, 95 %CI: 1.36–2.01), current ENDS-only use (AOR = 1.51, 95 %CI: 1.08–2.13), and current dual use (AOR = 2.29, 95 % CI: 1.56–3.48) were associated with higher odds of epilepsy after adjusting for demographic and health factors. Among adults with epilepsy, identifying as gay, lesbian, or bisexual was linked to higher odds of cigarette, ENDS, or dual use compared to straight individuals. Lower levels of education were associated with higher odds of cigarette smoking, while having health insurance was associated with lower odds among adults with epilepsy. Adults ≥ 35 were more likely to smoke cigarettes and less likely to use ENDS compared to younger age groups. ConclusionCigarette, ENDS, and dual use rates were higher in adults with epilepsy than in those without epilepsy. Social factors like sexual orientation, education, and insurance status further influence tobacco use within this population. Tailored cessation interventions are warranted for this vulnerable population to reduce disease burden.

NCMP-10. EFFECT OF EXTENT OF RESECTION ON GLIOMA SEIZURE OUTCOMES BASED ON MOLECULAR GROUPS

Abstract INTRODUCTION Increased extent of resection (EOR) is a known predictor of seizure freedom in glioma patients. However, it is unknown how tumor genomic alterations affect EOR-induced seizure control. OBJECTIVE To evaluate the genotype-specific impact of EOR on post-operative seizure control METHODS Records of 553 glioma patients who underwent tumor resection from 2012-2023 were reviewed. All patient tumors were analyzed with next generation sequencing and FISH analysis. The unsupervised machine learning algorithm non-negative matrix factorization (NMF) was used to cluster the genomic data. Clinical variables including extent of resection of contrast enhancing tumor and non-enhancing tumor, temozolomide therapy, and radiation therapy were analyzed using Cox Proportional Hazards models. RESULTS NMF clustering of tumor sequencing data revealed four molecular groups: Group 1 (n=56): CDKN2a loss, EGFR copy number gain or mutation, TERT promoter (TERTp) mutation, and MGMT methylated; Group 2 (n=27): IDH mutation, TP53 mutation, and MGMT methylated; Group 3 (n=60): TP53 mutation, TERTp mutation and MGMT methylated; Group 4 (n=244): MGMT unmethylated. Thresholds in the post-operative residual non-enhancing tumor volume (NETV) were identified which marked the most difference in seizure control. For patients in Group 1, the NETV threshold that led to improved epilepsy outcomes was &amp;lt;94.7 cc (p=0.047), whereas the threshold for Group 4 was &amp;lt;89.1 cc (p=0.016). When analysis was conducted for Group 2, the threshold of 10.2 cc failed to reach significance (p=0.1). Interestingly, the threshold analysis for Group 3 found that having a NETV of &amp;gt; 10.1 cc showed improved seizure outcomes (p=0.016). A multivariable cox proportional hazard analysis found that twelve-month seizure freedom was predictive of better OS in group 1 (HR 0.02, p=0.05) and group 4 (HR 0.21, p=1.63e-9). CONCLUSION Our study reveals clinically distinct molecular groups of glioma that display different seizure responses. This data suggests a tumor-specific approach to aggressiveness of extent of resection in order to achieve optimal seizure control.

Polygenic Risk of Epilepsy and Poststroke Epilepsy.

Epilepsy is highly heritable, with numerous known genetic risk loci. However, the genetic predisposition's role in poststroke epilepsy (PSE) remains understudied. This study assesses whether a higher genetic predisposition to epilepsy raises poststroke survivor's risk of PSE. We conducted a case-control genetic association study nested within the UK Biobank, a large UK-based prospective cohort. Our exposures of interest were 2 distinct polygenic risk scores-generalized and focal epilepsy-modeled as deciles and constructed using genetic variants identified in the latest International League Against Epilepsy genome-wide association study meta-analysis. We aimed to evaluate the association between these polygenic risk scores and their corresponding subtype of PSE-generalized and focal. In sensitivity analyses, we evaluated participants of European ancestry separately and considered focal and generalized epilepsy outcomes in participants without a history of stroke. In secondary analyses, we evaluated the polygenic risk of PSE by stroke subtype (ischemic, hemorrhagic, or any stroke). Multivariable logistic regression models were fitted, adjusting for age, sex, genetic ancestry, and the first 5 principal genetic components. Among 17 549 UK Biobank stroke survivors with available genetic information (mean age, 61; 43% female), 185 (1%) developed generalized PSE, while 124 (0.7%) developed focal PSE. Multivariable logistic regression results showed that, when compared against the lowest decile, participants within the highest PRS decile for generalized PSE had 5-fold higher odds of developing generalized PSE (OR, 5.05 [95% CI, 2.37-12.5]; P trend<0.001). Similarly, when compared against the lowest decile, participants within the highest polygenic risk score decile for focal PSE had 3-fold higher odds of developing focal PSE (OR, 3.20; [5% CI, 1.25-9.82]; P trend=0.024). Sensitivity analyses among participants of European ancestry yielded similar results. Our findings suggest that, like other forms of epilepsy, genetic predisposition plays an essential role in PSE. These results underscore the need for future studies to elucidate the mechanisms underlying PSE development and to identify novel therapeutic avenues.

Identifying the genetic association between severe autoimmune type 2 diabetes and the risk of focal epilepsy.

Observational studies suggested a bidirectional relationship between severe autoimmune type 2 diabetes and focal epilepsy. However, it remains debated whether and in which direction a causal association exists. This genetics-based study aimed to explore the relationships of severe autoimmune type 2 diabetes (T2DM) and focal epilepsy outcomes with two sample Mendelian randomization (TSMR) method. Genetic instruments were obtained from large-scale genome-wide meta-analysis of severe autoimmune T2DM (Ncase = 452, Ncontrol = 2,744), and focal epilepsy (Ncase = 929, Ncontrol = 212,532) of European ancestry. A series of analyses were performed to select eligible genetic instruments robustly associated with each of the traits using summary-level statistics. Inverse variance weighted was used for primary analysis, with alternative 11 MR methods. A scatter plot was utilized to illustrate the association between single nucleotide polymorphism (SNP) effects on the exposure and SNP effects on the outcome. The Wald ratio for individual SNPs and their cumulative effects was depicted using a forest plot. And diagnostics and sensitivity analyses were used to evaluate if the causal estimates are robust to violations of MR underlying assumptions, including pleiotropy, heterogeneity assessment, and leave-one-out analysis. Then the results were validated using CURATED database of DisGeNET platform. For forward analysis, genetic predisposition to severe autoimmune T2DM was associated with an increased risk of focal epilepsy (Inverse variance weighted (IVW) method: OR = 1.11, 95% CI = 1.03-1.18, p = 0.012). For reverse analysis, there was no enough instrument variables of focal epilepsy on severe autoimmune T2DM. Further, the interrelation between severe autoimmune T2DM and focal epilepsy was demonstrated via variant-disease association network analysis using the instrument SNPs. This MR study supports a causal link between severe autoimmune T2DM and focal epilepsy. More effort should be made to screen seizure in severe autoimmune T2DM, unravel its clinical implications, and explore its role as a putative modifiable risk factor.

Frontal lobe disconnection: How I do it.

The objective of frontal lobe disconnection (FD) is to isolate the frontal lobe without removing brain parenchyma, to achieve epilepsy outcomes comparable to those for frontal lobectomy but with fewer complications, since a large post-operative cavity is not created. Main surgical steps include "Identification of the central sulcus" to ensure the preservation of motor function, and "Frontal lobe disconnection" comprising: 1) fronto-parietal disconnection; 2) fronto-basal disconnection; 3) anterior corpus callosotomy; and 4) insula and basal ganglia disconnection. In performing FD, consideration of the disconnection boundary based on an anatomical understanding of white matter tracts is essential.

Overlap of spike and ripple propagation onset predicts surgical outcome in epilepsy.

Interictal biomarkers are critical for identifying the epileptogenic focus. However, spikes and ripples lack specificity while fast ripples lack sensitivity. These biomarkers propagate from more epileptogenic onset to areas of spread. The pathophysiological mechanism of these propagations is elusive. Here, we examine zones where spikes and high frequency oscillations co-occur (SHFO), the spatiotemporal propagations of spikes, ripples, and fast ripples, and evaluate the spike-ripple onset overlap (SRO) as an epilepsy biomarker. We retrospectively analyzed intracranial EEG data from 41 patients with drug-resistant epilepsy. We mapped propagations of spikes, ripples, and fast ripples, and identified their onset and spread zones, as well as SHFO and SRO. We then estimated the SRO prognostic value in predicting surgical outcome and compared it to onset and spread zones of spike, ripple, and fast ripple propagations, and SHFO. We detected spikes and ripples in all patients and fast ripples in 12 patients (29%). We observed spike and ripple propagations in 40 (98%) patients. Spike and ripple onsets overlapped in 35 (85%) patients. In good outcome patients, SRO showed higher specificity and precision (p < 0.05) in predicting resection compared to onset and zones of spikes, ripples, and SHFO. Only SRO resection predicted outcome (p = 0.01) with positive and negative predictive values of 82% and 57%, respectively. SRO is a specific and precise biomarker of the epileptogenic zone whose removal predicts outcome. SRO is present in most patients with drug-resistant epilepsy. Such a biomarker may reduce prolonged intracranial monitoring and improve outcome.

Clinical features, hemorrhage risk and epilepsy outcomes of familial cerebral cavernous malformation: A 20-year observational pragmatic single-center study

IntroductionFamilial Cerebral Cavernous Malformations (fCCMs) are rare, hereditary conditions characterized by multiple central nervous system lesions. Despite their rarity, CCMs can cause significant clinical challenges when symptomatic, manifesting as seizure and symptomatic hemorrhage (CASH). Guidelines suggest neurosurgical intervention for symptomatic or previously symptomatic lesions, while conservative management is recommended for new-onset epilepsy. However, the natural history and optimal management remain unclear, necessitating further research. ObjectiveThis study aims to provide a comprehensive analysis of the clinical features, hemorrhage risk, and epilepsy outcomes in fCCM patients over an extended follow-up period, offering a more precise estimate of CASH and epilepsy rates in this population. MethodsThis retrospective longitudinal cohort study included fCCM patients enrolled from 2001 to May 2024. Data collected included demographic information, new neurological symptoms, symptomatic hemorrhages, seizures, and modified Rankin Scale (mRS) scores. Incidence rates of first symptomatic events and Kaplan-Meier survival curves were calculated, with logistic and Cox-proportional hazard regression models used to evaluate outcomes. ResultsA total of 47 patients were included in this study, with a mean age at diagnosis of 37.51 years. At diagnosis, 68 % were symptomatic, with 30 % having CASH and 36 % experiencing seizures without CASH. During a median follow-up of 126.0 months (interquartile range, 110.5 months), 17 % had a new CASH event, 20 % had seizures without CASH, and 60 % remained asymptomatic. The bleeding rate was 1.02 % per patient-year, with new focal neurological symptoms at 2.045 per 1000 patient-years and new CASH at 10.225 per 1000 patient-years. Most patients maintained minimal or no disability (mRS 0 or 1). Presenting with epilepsy at baseline significantly increased the odds of future seizures (OR 18.13, p = 0.001). ConclusionThis study highlights the complex presentation and progression of fCCMs, emphasizing the necessity for long-term monitoring. Baseline epilepsy is a significant predictor of future seizures, underscoring the need for individualized management strategies. Future research with larger cohorts and standardized criteria is essential to refine the understanding and management of fCCMs.