Outcome Of Epilepsy Research Articles

Risk factors and outcome of epilepsy in adults with cerebral palsy or intellectual disability

IntroductionEpilepsy is found in 10–60% of individuals with cerebral palsy (CP) and 5.5–35% with intellectual disability (ID). However, little is known about the long-term evolution of epilepsy among adults. The aim of the study is to describe the factors associated with epilepsy and its outcome in a population of adults with CP or ID. MethodsThis retrospective study reviewed the medical records of 306 individuals with CP/ID. All individuals underwent neurological, psychiatric, and neuropsychological follow-ups. ResultsIn the cohort, 72.5% of the individuals had a CP diagnosis, with a mean age of 36.4 years (IQR 24.0–46.0). Epilepsy was present in 55.6% of the individuals and was associated with CP (p < 0.01), spastic subtype (p < 0.01), a higher degree of ID (p < 0.01), hemorrhagic and congenital malformation etiologies (p 0.011), abnormal neuroimaging (p < 0.01), and worse scores on motor and communication scales (p < 0.01). Drug-resistant epilepsy (DRE) (22.4%) was associated with higher scores on motor scales (p < 0.01). Additionally, 42.3% of the individuals who attempted antiseizure medication (ASM) withdrawal experienced recurrence, which was associated with epileptic activity on the electroencephalogram (EEG) (p 0.004). ConclusionsEpilepsy is a common comorbidity in adults with CP or ID and is associated with greater brain damage and a more severe phenotype. Seizure recurrence after ASM withdrawal occurred in half of the individuals and was associated with epileptic activity on the EEG.

Causal relationship between addictive behaviors and epilepsy risk: A mendelian randomization study

BackgroundPrevious studies have reported inconsistent results regarding the potential relationships between addictive behaviors and the risk of epilepsy. ObjectiveTo assess whether genetically predicted addictive behaviors are causally associated with the risk of epilepsy outcomes. MethodsThe causation between five addictive behaviors (including cigarettes per day, alcoholic drinks per week, tea intake, coffee intake, and lifetime cannabis use) and epilepsy was evaluated by using a two-sample Mendelian Randomization (MR) analysis. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (MR Egger, weighted median, simulation extrapolation corrected MR-Egger, and Mendelian Randomization Pleiotropy Residual Sum and Outlier (MR-PRESSO)) were performed to complement IVW. In addition, the robustness of the MR analysis results was assessed by leave-one-out analysis. ResultsThe IVW analysis method indicated an approximately 20% increased risk of epilepsy per standard deviation increase in lifetime cannabis use (odds ratio [OR], 1.20; 95% confidence interval [CI]), 1.02–1.42, P = 0.028). However, there is no causal association between the other four addictive behaviors and the risk of epilepsy (cigarettes per day: OR, 1.04; 95% CI, 0.92–1.18, P = 0.53; alcoholic drinks per week: OR, 1.31; 95% CI, 0.93–1.84, P = 0.13; tea intake: OR, 1.15; 95% CI, 0.84–1.56, P = 0.39; coffee intake: OR, 0.86; 95% CI, 0.59–1.23, P = 0.41). The other MR analysis methods and further leave-one-out sensitivity analysis suggested the results were robust. ConclusionThis MR study indicated a potential genetically predicted causal association between lifetime cannabis use and higher risk of epilepsy. As for the other four addictive behaviors, no evidence of a causal relationship with the risk of epilepsy was found in this study.

Genetic influences on epilepsy outcomes: A whole-exome sequencing and health care records data linkage study.

This study was undertaken to develop a novel pathway linking genetic data with routinely collected data for people with epilepsy, and to analyze the influence of rare, deleterious genetic variants on epilepsy outcomes. We linked whole-exome sequencing (WES) data with routinely collected primary and secondary care data and natural language processing (NLP)-derived seizure frequency information for people with epilepsy within the Secure Anonymised Information Linkage Databank. The study participants were adults who had consented to participate in the Swansea Neurology Biobank, Wales, between 2016 and 2018. DNA sequencing was carried out as part of the Epi25 collaboration. For each individual, we calculated the total number and cumulative burden of rare and predicted deleterious genetic variants and the total of rare and deleterious variants in epilepsy and drug metabolism genes. We compared these measures with the following outcomes: (1) no unscheduled hospital admissions versus unscheduled admissions for epilepsy, (2) antiseizure medication (ASM) monotherapy versus polytherapy, and (3) at least 1 year of seizure freedom versus <1 year of seizure freedom. We linked genetic data for 107 individuals with epilepsy (52% female) to electronic health records. Twenty-six percent had unscheduled hospital admissions, and 70% were prescribed ASM polytherapy. Seizure frequency information was linked for 100 individuals, and 10 were seizure-free. There was no significant difference between the outcome groups in terms of the exome-wide and gene-based burden of rare and deleterious genetic variants. We successfully uploaded, annotated, and linked genetic sequence data and NLP-derived seizure frequency data to anonymized health care records in this proof-of-concept study. We did not detect a genetic influence on real-world epilepsy outcomes, but our study was limited by a small sample size. Future studies will require larger (WES) data to establish genetic variant contribution to epilepsy outcomes.

Childhood-onset epilepsy in patients with dyskinetic cerebral palsy caused by basal ganglia and thalamic lesions

ObjectiveTo elucidate the incidence and outcomes of childhood-onset epilepsy and associated factors in term-born patients with basal ganglia and thalamic lesion (BGTL)-induced dyskinetic cerebral palsy (DCP) caused by perinatal hypoxic-ischemic encephalopathy (HIE). MethodsWe studied 104 term-born patients with BGTL-induced DCP (63 males and 41 females, aged 2–22 years) to investigate the incidence of epilepsy and the factors related to its development. We used multivariate analysis to assess perinatal factors, gross motor function, and the extent of brain lesions. We also investigated the seizure onset, clinical course, and electroencephalography (EEG) characteristics. ResultsThe cumulative epilepsy incidence was 36%. Multiple logistic regression analysis revealed that deep white matter lesions were the only independent risk factor for epilepsy. The confirmed seizure types included epileptic spasms (ES, n = 13), myoclonic seizures (MS, n = 6), and focal-onset seizures (FS, n = 24). Only patients with deep white matter lesions exhibited ES or MS. The symptoms of FS resembled those of self-limited epilepsy with centrotemporal spikes; however, only half of the patients reached remission by the time of investigation, and four patients had more than one seizure per month despite appropriate drug therapy. Focal spikes in the peri-rolandic area were detected not only in patients with FS but also in half of the patients without epilepsy. ConclusionsOne-third of term-born patients with BGTL-induced DCP caused by perinatal HIE develop epilepsy, and deep white matter lesions increase the likelihood of epilepsy. Preparation for early-onset ES, MS, and subsequent FS is beneficial.

Surgical Outcomes in Post-Traumatic Temporal Lobe Epilepsy: A Systematic Review and Meta-Analysis.

Epilepsy surgery provides excellent benefits in post-traumatic epilepsy of the temporal lobe (PTE-TL), but outcomes relative to non-traumatic epilepsy of the temporal lobe (NTE-TL) are less favorable. Large well-designed studies are recommended to further clarify the role of epilepsy surgery in PTE. It is unclear whether epilepsy surgery outcomes in PTE are as robust as described for drug resistant epilepsy (DRE) in general. Prior outcome studies in PTE are limited by small numbers, lack of a control group, or both. We performed a meta-analysis of studies in temporal lobe epilepsy (TLE) to evaluate post-surgical outcomes in those with PTE-TL and compare outcomes to those with NTE-TL. PubMed, EMBASE, and Web of Science databases were queried for studies reporting epilepsy surgery outcomes separately for PTE-TL and NTE-TL. Outcomes were divided into favorable (Engel Class I) or unfavorable (Engel Class II-IV) for comparison. Meta-analyses were performed to evaluate: 1) the proportion of Class I outcomes following epilepsy surgery in PTE-TL; and 2) calculate the odds of Class I surgical outcomes in PTE-TL compared with NTE-TL. Of 3669 articles that reported surgical outcomes in epilepsy, nine studies (n = 886) were identified that reported outcomes for both PTE-TL (n = 219) and NTE-TL (n = 667). The weighted proportion of favorable outcomes (Engel Class I) were high for both PTE-TL (70.1%, 95% CI 61.9%-78.3%) and NTE-TL (75.2%, 95% CI 69.4%-80.2%). Patients with PTE-TL were at greater risk of unfavorable (Engel Class II-IV) outcomes (relative risk 1.36, 95% CI 1.04-1.78) compared with NTE-TL.

Patterns of neurobehavioral functioning in school-aged survivors of neonatal jaundice and hypoxic-ischemic encephalopathy in Kilifi, Kenya: A cross-sectional study

Background: Studies in high-income countries have reported that school-aged children who survive neonatal jaundice (NNJ) and hypoxic-ischemic encephalopathy (HIE) develop long-term neurocognitive problems. However, less is known about the patterns of functioning in school-aged survivors of NNJ and HIE in sub-Saharan Africa. This study examined patterns of functioning in school-aged children who survived NNJ and HIE in Kilifi, Kenya. Methods: This is a cross-sectional study that included 107 survivors of NNJ/HIE (64 with NNJ, 43 with HIE), aged 6-12 years, admitted to Kilifi County Hospital on the Kenyan Coast. The Gross Motor Function Classification System (GMFCS), Adapted Communication Profile, Raven’s Coloured Progressive Matrices (RCPM) and an epilepsy screening tool were used to assess gross motor function, communication function, intellectual functioning, and epilepsy, respectively. Results: Most of the survivors of NNJ (95.2%) and HIE (95.3%) had no impairments in gross motor functioning. A small percentage of the children in the NNJ and HIE groups had profound problems in their communication (4.7% and 4.7%); expressive communication function (4.7% and 4.7%); social functions (3.1% and 2.3%); receptive communication (4.7% and 2.3%); and communicative effectiveness (4.7% and 2.3%). Cognitive impairment was reported in 10.9% and 11.9% for NNJ and HIE survivors, respectively. Active epilepsy was detected in 1.6% of survivors of NNJ and 2.3% of survivors of HIE. A subgroup of severe NNJ and HIE survivors without co-occurring conditions had the worst intellectual and active epilepsy outcomes. All children had normal hearing and visual functioning except one participant who presented with mild visual acuity problems. Conclusions: Most school-aged children who survive with NNJ and HIE have normal motor and communication function; however, one in ten are likely to present with lowered intellectual functioning compared to the normative sample.

Prognostic factors for employment outcomes in patients with a history of childhood-onset drug-resistant epilepsy.

The employment outcomes of childhood-onset drug-resistant epilepsy (DRE) has not been studied enough. The aim of this retrospective cohort study is to investigate the employment outcomes of childhood-onset DRE in June 2022 and identify the risk factors associated with non-employment. The sample consisted of 65 participants ≥18 years of age with a history of childhood-onset DRE. Fifty participants (77%) were salaried employees and 15 participants (23%) were non-employed. Clinical and psychosocial information were evaluated for calculating the relative risk (RR) of non-employment. Regarding medical factors, lower IQ [RR, 0.645; 95% confidence interval (CI), 0.443-0.938; p = 0.022] was positively associated with employment. In contrast, age at follow-up (RR, 1.046; 95% CI, 1.009-1.085; p = 0.014); number of ASMs at follow-up (RR, 1.517; 95% CI, 1.081-2.129; p = 0.016); use of medications such as phenobarbital (RR, 3.111; 95% CI, 1.383-6.997; p = 0.006), levetiracetam (RR, 2.471; 95% CI, 1.056-5.782; p = 0.037), and topiramate (RR, 3.576; 95% CI, 1.644-7.780; p = 0.001) were negatively associated with employment. Regarding psychosocial factor, initial workplace at employment support facilities (RR, 0.241; 95% CI, 0.113-0.513; p < 0.001) was positively associated with employment. In contrast, complication of psychiatric disorder symptoms (RR, 6.833; 95% CI, 2.141-21.810; p = 0.001) was negatively associated with employment. Regarding educational factor, graduating schools of special needs education (RR, 0.148; 95% CI, 0.061-0.360; p < 0.001) was positively associated with employment. Specific medical, psychosocial, and educational factors may influence the employment outcomes of childhood-onset DRE. Paying attention to ASMs' side effects, adequately preventing the complications of psychiatric disorder symptoms, and providing an environment suitable for each patient condition would promote a fine working status for people with childhood-onset DRE.

Outcome of Absence Epilepsy With Onset at 8-11 Years of Age: Watershed Ages When Syndromes Overlap.

Introduction: Absence seizures occur in various epilepsy syndromes, including childhood and juvenile absence epilepsy and juvenile myoclonic epilepsy. When children present with absence seizures at ages when syndromes overlap, initial syndrome designation is not always possible, making early prognostication challenging. For these children, the study objective is to determine clinical and initial electroencephalograph (EEG) findings to predict the development of generalized tonic-clonic seizures, which is a factor that affects outcome. Methods: Children with new-onset absence seizures between 8 and 11 years of age with at least 5 years of follow-up data were studied through the review of medical records and initial EEG tracings. Results: Ninety-eight patients were included in the study. The median age of absence seizure onset was 9 years (interquartile range [IQR] = 8.00, 10.00) and follow-up was 15 years (IQR = 13.00, 18.00). Forty-six percent developed generalized tonic-clonic seizures and 20% developed myoclonic seizures. On multiple regression analysis, a history of myoclonic seizures, anxiety, as well as bifrontal slowing and mild background slowing on initial EEG (P < .05) were associated with generalized tonic-clonic seizures. Although not statistically significant, a shorter duration of shortest EEG burst on baseline EEG was also associated with generalized tonic-clonic seizures. Conclusion: On initial EEG, bifrontal and background slowing and myoclonic seizures and anxiety are associated with developing generalized tonic-clonic seizures, which is of prognostic significance when early syndrome designation is difficult.

Resective epilepsy surgery in a limited-resource settings: A cohort from a multi-disciplinary epilepsy team in a developing country.

Multidisciplinary pre-surgical evaluation is vital for epilepsy surgery decision and outcomes. Resective epilepsy surgery with assisted monitoring is currently a standard treatment for focal drug resistant epilepsy (DRE). In resource-limited countries, lack of epilepsy surgery center is a huge challenge. We presented and illustrated how to create a multidisciplinary protocol with resource-limited settings in a developing country and epilepsy surgery outcome using brain mapping and monitoring techniques for ensuring satisfactory resection. We created multicentric incomplete but complementary units covering all epilepsy-related sub-specialties and covering a wide geographical area in our country. Then, we conducted a prospective and multicentric study with low resource settings on patients with focal DRE, who underwent resective epilepsy surgery and were followed up for at least 12 months and were evaluated for postoperative seizure outcome and complications if present. Preoperative comprehensive clinical, neurophysiological, neuropsychological, and radiological evaluations were performed by multidisciplinary epilepsy team. Intraoperative brain mapping including awake craniotomy and direct stimulation techniques, neurophysiological monitoring, and electrocorticography was carried out during surgical resection. The study included 47 patients (18 females and 29 males) with mean age 20.4 ± 10.02 years. Twenty-two (46.8%) patients were temporal epilepsy while 25 (53.2%) were extra-temporal epilepsy. The epilepsy surgery outcome at the last follow up was Engel Class I (seizure free) in 35 (74.5%), Class II (almost seizure free) in 8 (17%), Class III (worthwhile improvement) in 3 (6.4%), and Class IV (no worthwhile improvement) in 1 patient (2.1%). With low resource settings and lack of single fully equipped epilepsy center, favorable outcomes after resective surgery in patients with focal DRE could be achieved using careful presurgical multidisciplinary selection, especially with using intraoperative brain mapping and electrocorticography techniques.

Association of neighborhood deprivation with white matter connectome abnormalities in temporal lobe epilepsy.

Social determinants of health, including the effects of neighborhood disadvantage, impact epilepsy prevalence, treatment, and outcomes. This study characterized the association between aberrant white matter connectivity in temporal lobe epilepsy (TLE) and disadvantage using a US census-based neighborhood disadvantage metric, the Area Deprivation Index (ADI), derived from measures of income, education, employment, and housing quality. Participants including 74 TLE patients (47 male, mean age = 39.2 years) and 45 healthy controls (27 male, mean age = 31.9 years) from the Epilepsy Connectome Project were classified into ADI-defined low and high disadvantage groups. Graph theoretic metrics were applied to multishell connectome diffusion-weighted imaging (DWI) measurements to derive 162 × 162 structural connectivity matrices (SCMs). The SCMs were harmonized using neuroCombat to account for interscanner differences. Threshold-free network-based statistics were used for analysis, and findings were correlated with ADI quintile metrics. A decrease in cross-sectional area (CSA) indicates reduced white matter integrity. Sex- and age-adjusted CSA in TLE groups was significantly reduced compared to controls regardless of disadvantage status, revealing discrete aberrant white matter tract connectivity abnormalities in addition to apparent differences in graph measures of connectivity and network-based statistics. When comparing broadly defined disadvantaged TLE groups, differences were at trend level. Sensitivity analyses of ADI quintile extremes revealed significantly lower CSA in the most compared to least disadvantaged TLE group. Our findings demonstrate (1) the general impact of TLE on DWI connectome status is larger than the association with neighborhood disadvantage; however, (2) neighborhood disadvantage, indexed by ADI, revealed modest relationships with white matter structure and integrity on sensitivity analysis in TLE. Further studies are needed to explore this relationship and determine whether the white matter relationship with ADI is driven by social drift or environmental influences on brain development. Understanding the etiology and course of the disadvantage-brain integrity relationship may serve to inform care, management, and policy for patients.

Tumor-related epilepsy and post-surgical outcomes: tertiary hospital experience in Vietnam

Seizures have a significant impact on the quality of life of those who suffer. This study aimed to evaluate the variables that influence the incidence of seizures during the perioperative period and effective measures to enhance epilepsy outcomes among individuals undergoing surgical resection of brain tumors. The authors carried out a prospective observational analysis of all patients who experienced seizures before their brain tumor surgery at UMC, HCMC between 2020 and 2022. 54 cases presented with seizures were enrolled for the study, generalized seizure was the most prevalent seizure type (61.1%), followed by focal seizure (29.6%). The majority of patients presented with seizures are those who were diagnosed with glioma. Low-grade gliomas and frontotemporal lobe tumors increase the postoperative risk of seizure. Other predictive factors are a prolonged history of seizure, especially resistant epilepsy and major peritumoral edema. In contrast, gross total resection reduces postoperative seizure incidence. There was correlation between Ki67 proliferation index and seizure incidence in both low-grade and high-grade gliomas. ECoG made insubstantial difference in enhancing the epilepsy surgery outcome. Overall, 88.9% of patients were seizure-free at 6 months of follow-up (Engel Class I), 7.4% were almost seizure-free (Class II), and 3.7% had significant improvement (Class III), figures for 12-month follow-up were 87.0%, 9.3%, and 3.7% respectively. A shorter history of seizure and gross-total resection appear to be associated with a favorable prognosis for seizure control.

Ictal EEG desynchronization during low-voltage fast activity for prediction of surgical outcomes in focal epilepsy.

The authors investigated alterations in functional connectivity (FC) and EEG power during ictal onset patterns of low-voltage fast activity (LVFA) in drug-resistant focal epilepsy. They hypothesized that such changes would be useful to classify epilepsy surgical outcomes. In a cohort of 79 patients with drug-resistant focal epilepsy who underwent stereoelectroencephalography (SEEG) evaluation as well as resective surgery, FC changes during the peri-LVFA period were measured using nonlinear regression (h2) and power spectral properties within/between three regions: the seizure onset zone (SOZ), early propagation zone (PZ), and noninvolved zone (NIZ). Desynchronization and power desynchronization h2 indices were calculated to assess the degree of EEG desynchronization during LVFA. Multivariate logistic regression was employed to control for confounding factors. Finally, receiver operating characteristic curves were generated to evaluate the performance of desynchronization indices in predicting surgical outcome. Fifty-three patients showed ictal LVFA and distinct zones of the SOZ, PZ, and NIZ. Among them, 39 patients (73.6%) achieved seizure freedom by the final follow-up. EEG desynchronization, measured by h2 analysis, was found in the seizure-free group during LVFA: FC decreased within the SOZ and between regions compared with the pre-LVFA and post-LVFA periods. In contrast, the non-seizure-free group showed no prominent EEG desynchronization. The h2 desynchronization index, but not the power desynchronization index, enabled classification of seizure-free versus non-seizure-free patients after resective surgery. EEG desynchronization during the peri-LVFA period, measured by within-zone and between-zone h2 analysis, may be helpful for identifying patients with favorable postsurgical outcomes and also may potentially improve epileptogenic zone identification in the future.

Resective Epilepsy Surgery, QUality of life and Economic evaluation (RESQUE): the change in quality of life after resective epilepsy surgery–protocol for a multicentre, prospective cohort study

IntroductionResective epilepsy surgery is often seen as a last resort when treating drug-resistant epilepsy. Positive results on quality of life (QoL) and economic benefits after surgery argue for a less...

Predicting Drug Treatment Outcomes in Childrens with Tuberous Sclerosis Complex-Related Epilepsy: A Clinical Radiomics Study.

Highly predictive markers of drug treatment outcomes of tuberous sclerosis complex-related epilepsy are a key unmet clinical need. The objective of this study was to identify meaningful clinical and radiomic predictors of outcomes of epilepsy drug treatment in patients with tuberous sclerosis complex. A total of 105 children with tuberous sclerosis complex-related epilepsy were enrolled in this retrospective study. The pretreatment baseline predictors that were used to predict drug treatment outcomes included patient demographic and clinical information, gene data, electroencephalogram data, and radiomic features that were extracted from pretreatment MR imaging scans. The Spearman correlation coefficient and least absolute shrinkage and selection operator were calculated to select the most relevant features for the drug treatment outcome to build a comprehensive model with radiomic and clinical features for clinical application. Four MR imaging-based radiomic features and 5 key clinical features were selected to predict the drug treatment outcome. Good discriminative performances were achieved in testing cohorts (area under the curve = 0.85, accuracy = 80.0%, sensitivity = 0.75, and specificity = 0.83) for the epilepsy drug treatment outcome. The model of radiomic and clinical features resulted in favorable calibration curves in all cohorts. Our results suggested that the radiomic and clinical features model may predict the epilepsy drug treatment outcome. Age of onset, infantile spasms, antiseizure medication numbers, epileptiform discharge in left parieto-occipital area of electroencephalography, and gene mutation type are the key clinical factors to predict the epilepsy drug treatment outcome. The texture and first-order statistic features are the most valuable radiomic features for predicting drug treatment outcomes.

Disconnection Surgery in Pediatric Epilepsy: A Single Center's Experience With 185 Cases.

Lobar and multilobar disconnections have gradually become common surgical methods in pediatric epilepsy surgery in recent years. However, the surgical procedures, postoperative epilepsy outcomes, and complications reported by each center are quite different. To review and analyze the clinical data from lobar disconnection in treating intractable pediatric epilepsy and study the characteristics, surgical outcomes, and safety of different disconnection surgeries. This was a retrospective analysis of 185 children with intractable epilepsy who underwent various lobar disconnections at the Pediatric Epilepsy Center, Peking University First Hospital. Clinical information was grouped according to their characteristics. The differences in the abovementioned characteristics among the different lobar disconnections were summarized, and risk factors affecting the surgical outcome and postsurgical complications were explored. Among the 185 patients, 149 patients (80.5%) achieved seizure freedom with a follow-up of 2.1 years. There were 145 patients (78.4%) with malformations of cortical development (MCD). The seizure onset time (median 6 months, P = .001) and surgery time (median 34 months, P = .000) of the MCD group were smaller. Differences were found in etiology, resection of the insular lobe and epilepsy outcome among different disconnection approaches. Both parieto-occipital disconnection ( P = .038, odds ratio = 8.126) and MRI abnormalities larger than the disconnection extent ( P = .030, odds ratio = 2.670) affected the epilepsy outcome. Early postoperative complications were observed in 43 patients (23.3%), and long-term postoperative complications were observed in 5 patients (2.7%). The most common etiology of epilepsy in children undergoing lobar disconnection is MCD, whose onset and operative ages are the youngest. Disconnection surgery obtained good seizure outcomes in the treatment of pediatric epilepsy with a low incidence of long-term complications. With advances in presurgical evaluation, disconnection surgery will play a more important role in young children with intractable epilepsy.

Altered metabolic-functional coupling in the epileptogenic network could predict surgical outcomes of mesial temporal lobe epilepsy.

To investigate the relationship between glucose metabolism and functional activity in the epileptogenic network of patients with mesial temporal lobe epilepsy (MTLE) and to determine whether this relationship is associated with surgical outcomes. 18F-FDG PET and resting-state functional MRI (rs-fMRI) scans were performed on a hybrid PET/MR scanner in 38 MTLE patients with hippocampal sclerosis (MR-HS), 35 MR-negative patients and 34 healthy controls (HC). Glucose metabolism was measured using 18F-FDG PET standardized uptake value ratio (SUVR) relative to cerebellum; Functional activity was obtained by fractional amplitude of low-frequency fluctuation (fALFF). The betweenness centrality (BC) of metabolic covariance network and functional network were calculated using graph theoretical analysis. Differences in SUVR, fALFF, BC and the spatial voxel-wise SUVR-fALFF couplings of the epileptogenic network, consisting of default mode network (DMN) and thalamus, were evaluated by Mann-Whitney U test (using the false discovery rate [FDR] for multiple comparison correction). The top ten SUVR-fALFF couplings were selected by Fisher score to predict surgical outcomes using logistic regression model. The results showed decreased SUVR-fALFF coupling in the bilateral middle frontal gyrus (PFDR = 0.0230, PFDR = 0.0296) in MR-HS patients compared to healthy controls. Coupling in the ipsilateral hippocampus was marginally increased (PFDR = 0.0802) in MR-HS patients along with decreased BC of metabolic covariance network and functional network (PFDR = 0.0152; PFDR = 0.0429). With Fisher score ranking, the top ten SUVR-fALFF couplings in regions from DMN and thalamic subnuclei could predict surgical outcomes with the best performance being a combination of ten SUVR-fALFF couplings with an AUC of 0.914. These findings suggest that the altered neuroenergetic coupling in the epileptogenic network is associated with surgical outcomes of MTLE patients, which may provide insight into their pathogenesis and help with preoperative evaluation.

1019 New onset OSA after long term Vagus Nerve Stimulator implantation in a patient with Lennox-Gastaut syndrome: A case report

Abstract Introduction Implantable vagus nerve stimulation (VNS) is an established treatment for drug resistant epilepsy. New onset obstructive sleep apnea (OSA) is a rare side effect of VNS. There are few studies describing VNS induced sleep apnea in adults. [1-2] A study of 16 patients with drug-refractory epilepsy found 5 patients with normal AHI develop mild OSA after VNS treatment for 3 months. [2] However, no literature exists regarding OSA after long term VNS implantation. Untreated OSA in patients with epilepsy can impact epilepsy outcomes. We report a case of new onset OSA after long term VNS implantation, refractory to PAP therapy. Report of case(s) A 36 year-old man with Lennox-Gastaut syndrome presented with gasping during sleep and daytime hypersomnolence. He underwent VNS implantation at the age of 12. A prior PSG in 2018 showed no sleep apnea. Repeat PSG showed VNS-induced OSA (AHI 10.1/hour). After failed CPAP titration, BPAP-S at 25/16 cm H2O improved OSA. Review of therapy data on follow up showed AHI of 13.7/hour and CAI of 10.9/hour, which is concerning for treatment induced central sleep apnea on BPAP. Diagnostic study with VNS turned off revealed mild OSA (AHI 5.8/hour). A multidisciplinary approach involving ENT for drug-induced sleep endoscopy to optimize VNS stimulation parameters along with neurology and sleep involvement is planned. The optimized VNS setting could be used during planned sleep times using a VNS device with dual-programming capability. Conclusion To our knowledge, there is no literature on development of sleep apnea after long term VNS implantation. Although the exact mechanism is unknown, VNS can cause sleep apnea or worsen sleep apnea in patients with a preexisting diagnosis. [1] This case demonstrates need for continuous monitoring and screening for sleep apnea in patients who have been implanted with VNS, even if baseline and follow up PGSs are normal. Current literature suggests discontinuation of VNS to resolve VNS-induced OSA, but we describe a case here where VNS is needed for ongoing management of epilepsy. Further studies are needed to identify treatment options for patients that cannot discontinue VNS therapy who also cannot be successfully treated with PAP if they develop VNS-induced OSA. Support (if any)

Commentary: Consensus Guidelines on the Appropriate Use of Brand-Name and Generic Anti-Seizure Medication for the Management of Epilepsy in the Gulf Region.

The clinical, social, and economic burden of epilepsy is undeniable. Local guidance on epilepsy management is limited and needed to address the both use of anti-seizure medication (ASM) and switching practices which influence clinical outcomes. An expert panel composed of practicing neurologists and epileptologists from countries of the Gulf Cooperation Council (GCC) met in 2022 to discuss local challenges in the management of epilepsy and formulate recommendations for clinical practice. Published literature on the outcomes of ASM switching was reviewed along with clinical practice/gaps, international guidelines, and local treatment availabilities. Improper ASM use and inappropriate brand-name-to-generic or generic-to-generic switching can contribute to worsening clinical outcomes in epilepsy. ASMs should be used for the management of epilepsy based on patient clinical profile, underlying epilepsy syndrome, and drug availability to ensure optimal and sustainable treatment. Both first-generation and newer ASMs can be considered; appropriate use is recommended from the beginning of treatment. It is critical to avoid inappropriate ASM switching to avoid breakthrough seizures. All generic ASMs should fulfill strict regulatory requirements. If needed, ASM changes should always be approved by the treating physician. ASM switching (brand-name-to-generic, generic-to-generic, generic-to-brand-name) should be avoided in epilepsy patients who have achieved control but can be considered for those uncontrolled on current medication.

Long-term epilepsy outcome dynamics revealed by natural language processing of clinic notes.

Electronic medical records allow for retrospective clinical research with large patient cohorts. However, epilepsy outcomes are often contained in free text notes that are difficult to mine. We recently developed and validated novel natural language processing (NLP) algorithms to automatically extract key epilepsy outcome measures from clinic notes. In this study, we assessed the feasibility of extracting these measures to study the natural history of epilepsy at our center. We applied our previously validated NLP algorithms to extract seizure freedom, seizure frequency, and date of most recent seizure from outpatient visits at our epilepsy center from 2010 to 2022. We examined the dynamics of seizure outcomes over time using Markov model-based probability and Kaplan-Meier analyses. Performance of our algorithms on classifying seizure freedom was comparable to that of human reviewers (algorithm F1 = .88 vs. human annotator = .86). We extracted seizure outcome data from 55 630 clinic notes from 9510 unique patients written by 53 unique authors. Of these, 30% were classified as seizure-free since the last visit, 48% of non-seizure-free visits contained a quantifiable seizure frequency, and 47% of all visits contained the date of most recent seizure occurrence. Among patients with at least five visits, the probabilities of seizure freedom at the next visit ranged from 12% to 80% in patients having seizures or seizure-free at the prior three visits, respectively. Only 25% of patients who were seizure-free for 6 months remained seizure-free after 10 years. Our findings demonstrate that epilepsy outcome measures can be extracted accurately from unstructured clinical note text using NLP. At our tertiary center, the disease course often followed a remitting and relapsing pattern. This method represents a powerful new tool for clinical research with many potential uses and extensions to other clinical questions.

Variation in prognosis and treatment outcome in juvenile myoclonic epilepsy: a Biology of Juvenile Myoclonic Epilepsy Consortium proposal for a practical definition and stratified medicine classifications.

Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes. Our study is based on clinical data collected by the Biology of Juvenile Myoclonic Epilepsy Consortium augmented by literature data. We review prognosis research on mortality and seizure remission, predictors of antiseizure medication resistance and selected adverse drug events to valproate, levetiracetam and lamotrigine. Based on our analysis, a simplified set of diagnostic criteria for juvenile myoclonic epilepsy includes the following: (i) myoclonic jerks as mandatory seizure type; (ii) a circadian timing for myoclonia not mandatory for the diagnosis of juvenile myoclonic epilepsy; (iii) age of onset ranging from 6 to 40 years; (iv) generalized EEG abnormalities; and (v) intelligence conforming to population distribution. We find sufficient evidence to propose a predictive model of antiseizure medication resistance that emphasises (i) absence seizures as the strongest stratifying factor with regard to antiseizure medication resistance or seizure freedom for both sexes and (ii) sex as a major stratifying factor, revealing elevated odds of antiseizure medication resistance that correlates to self-report of catamenial and stress-related factors including sleep deprivation. In women, there are reduced odds of antiseizure medication resistance associated with EEG-measured or self-reported photosensitivity. In conclusion, by applying a simplified set of criteria to define phenotypic variations of juvenile myoclonic epilepsy, our paper proposes an evidence-based definition and prognostic stratification of juvenile myoclonic epilepsy. Further studies in existing data sets of individual patient data would be helpful to replicate our findings, and prospective studies in inception cohorts will contribute to validate them in real-world practice for juvenile myoclonic epilepsy management.