Incomplete resection of the intracranial electroencephalographic seizure onset zone is not associated with postsurgical outcomes.

Delineation of seizure onset regions using intracranial electroencephalography (icEEG) is vital in the surgical workup of drug-resistant epilepsy cases. However, it is unknown whether the complete resection of these regions is necessary for seizure freedom, or whether postsurgical seizure recurrence can be attributed to the incomplete removal of seizure onset regions. To address this gap, we retrospectively analyzed icEEG recordings from 63 subjects, identifying seizure onset regions visually and algorithmically. We assessed onset region resection and correlated this with postsurgical seizure control. The majority of subjects had more than half of their onset regions resected (82.46% and 80.65% of subjects using visual and algorithmic methods, respectively). There was no association between the proportion of the seizure onset zone (SOZ) that was subsequently resected and better surgical outcomes (area under the receiver operating characteristic curve [AUC] < .7). Investigating the spatial extent of onset regions, we found no substantial evidence of an association with postsurgical seizure control (all AUC < .7). Although seizure onset regions are typically resected completely or in large part, incomplete resection is not associated with worse postsurgical outcomes. We conclude that postsurgical seizure recurrence cannot be attributed to an incomplete resection of the icEEG SOZ alone. Other network mechanisms beyond icEEG seizure onset likely contribute.

Cognitive behavioral therapy in adults with functional seizures: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Randomized controlled clinical trials (RCTs) investigating cognitive-behavioral therapy (CBT) among adults with functional seizures (FS) have become increasingly available, prompting the opportunity to critically appraise the efficacy and safety of CBT in this population. METHODS: We conducted a systematic review and meta-analysis including RCTs comparing CBT in addition to standardized medical treatment (SMT) versus SMT alone for adults with FS. The primary outcome was seizure freedom at the end of treatment. Secondary outcomes included measures of quality of life, anxiety and depression assessed via standardized clinical questionnaires. RESULTS: Three RCTs were included comprising 228 participants treated with CBT and 222 with SMT. The intervention was significantly associated with seizure freedom (Odds Ratio [OR] 1.98; 95 % confidence interval [CI] 1.14, 3.46; p = 0.02; I2 = 0 %), reductions in anxiety (standardized mean difference [SMD] -0.21; 95 % CI -0.41, -0.003; p = 0.047; I2 = 0 %) and improvements in quality of life (SMD 0.34; 95 % CI 0.12, 0.57; p = 0.003; I2 = 0 %) at the end of treatment. Conversely, no significant differences between groups were observed in depression symptoms (SMD -0.19; 95 % CI -0.39, 0.02; p = 0.08; I2 = 0 %). There was no statistically significant increase in the risk of suicidal ideation and self-harm with CBT (OR 2.11; 95 % CI 0.81, 5.48; p = 0.13; I2 = 0 %) nor were there differences in terms of discontinuation rates during follow-up (OR 0.92; 95 % CI 0.49, 1.72; p = 0.79; I2 = 7 %). CONCLUSIONS: There is high-quality evidence supporting the efficacy and safety of CBT in treating FS. Future research should investigate whether combining CBT with other therapeutic methods could potentially enhance treatment efficacy.

MRI and pathology comparisons in Rasmussen's encephalitis: a multi-institutional examination of hemispherotomy outcomes relative to imaging and histological severity.

PURPOSE: Rasmussen encephalitis (RE) is a very rare chronic neurological disorder of unilateral inflammation of the cerebral cortex. Hemispherotomy provides the best chance at achieving seizure freedom in RE patients, but with significant risks and variable long-term outcomes. The goal of this study is to utilize our multicenter pediatric cohort to characterize if differences in pathology and/or imaging characterization of RE may provide a window into post-operative seizure outcomes, which in turn could guide decision-making for parents and healthcare providers. METHODS: This multi-institutional retrospective review of medical record, imaging, and pathology samples was approved by each individual institution's review board. Data was collected from all known pediatric cases of peri-insular functional hemispherotomy from the earliest available electronic medical records. Mean follow-up time was 4.9 years. Clinical outcomes were measured by last follow-up visit using both Engel and ILAE scoring systems. Relationships between categorical and continuous variables were analyzed with Pearson correlation values. RESULTS: Twenty-seven patients met study criteria. No statistically significant correlations existed between patient imaging and pathology data. Pathology stage, MRI brain imaging stages, and a combined assessment of pathology and imaging stages showed no statistically significant correlation to post-operative seizure freedom rates. Hemispherectomy Outcome Prediction Scale scoring demonstrated seizure freedom in only 71% of patients receiving a score of 1 and 36% of patients receiving a score of 2 which were substantially lower than predicted. CONCLUSIONS: Our analysis did not find evidence for either independent or combined analysis of imaging and pathology staging being predictive for post peri-insular hemispherotomy seizure outcomes, prompting the need for other biomarkers to be explored. Our data stands in contrast to the recently proposed Hemispherectomy Outcome Prediction Scale and does not externally validate this metric for an RE cohort.

Predicting seizure outcomes and functional outcomes after hemispherotomy: are we any better?

INTRODUCTION: Present study attempted to analyze seizure freedom and detailed functional outcomes after functional hemispherotomy and utility of hemispherotomy outcome prediction scale (HOPS) scores in predicting outcomes. METHODS: Patients who underwent functional hemispherotomy were analyzed for clinical presentation, neuroimaging, seizure outcomes, and functional outcomes. RESULTS: A total of 76 procedures were performed on 69 patients. Mean age at the surgery was 8 ± 6.1 years. Fourteen patients were < 2 years. Age of onset epilepsy of the cohort was 2.0 ± 3.3 years. All had severe catastrophic epilepsy with multiple daily seizures. All patients had motor deficits with 36 (52%) patients had contralateral dysfunctional hand. Perinatal stroke (49%) was most common substrate followed by cortical malformations (21.7%). Eight patients had contralateral imaging abnormalities. Fifty-nine (86.76%) patients remained seizure free (Engle 1a) at 41 + -20.9 months. HOPS scores were available for 53 patients and lowest seizure outcome was 71% for HOPS score of 4. Lower HOPS scores predicted better seizure outcomes. Cortical malformations operated earlier than 2 years predicted poor seizure outcomes (66.6%). Positive functional outcomes are recorded in 80% of patients with 78% reporting improvement from the pre-surgical level. Five (7.2%) patients underwent shunt surgery. One mortality recorded. CONCLUSIONS: Hemispherotomy has excellent seizure outcomes. Early surgery in cortical malformations appears to be predictor of poorer seizure outcomes. HOPS score is a good tool to predict the seizure outcomes. Hemispherotomy is perceived to improve the Cognitive and functional performance.

[Discontinuation of antiseizure medication in patients with epilepsy]. / Absetzen anfallssuppressiver Medikamente bei Patient*innen mit Epilepsie.

BACKGROUND: Approximately two thirds of patients with epilepsy become seizure-free with antiseizure medication (ASM). A central question is whether and when ASM can be discontinued. OBJECTIVE: To present an overview of the current knowledge about risks and benefits of discontinuation of ASM. MATERIAL AND METHODS: Review of the current literature, discussion of data on and recommendations for discontinuation of ASM. RESULTS: The risk of seizure recurrence after discontinuation of ASM is approximately 40-50% and thus twice as high as continuing with ASM. Guidelines recommend considering discontinuation of ASM at earliest after a seizure-free period of 2 years. Predictive variables for seizure recurrence after stopping ASM include longer duration of epilepsy and higher number of seizures until remission, a shorter seizure-free interval until stopping ASM, older age at epilepsy onset, developmental delay or IQ < 70, febrile seizures in childhood, absence of a self-limiting epilepsy syndrome, and evidence of epileptiform activity in the electroencephalograph (EEG). The individual risk of seizure recurrence after stopping ASM can be estimated using an online prediction tool. CONCLUSION: Discontinuation of ASM should be discussed with patients at the earliest after 2 years of seizure freedom in a shared decision-making process weighing up the risks and benefits. The risk of a seizure recurrence depends on a number of clinical variables. Psychosocial aspects, such as impact on driving and occupational issues must be taken into consideration as well as individual fears and concerns of patients about seizure recurrence or the long-term use of ASM.

Beyond seizure freedom: Dissecting long-term seizure control after surgical resection for drug-resistant epilepsy.

OBJECTIVE: This study was undertaken to better understand the long-term palliative and disease-modifying effects of surgical resection beyond seizure freedom, including frequency reduction and both late recurrence and remission, in patients with drug-resistant epilepsy. METHODS: This retrospective database-driven cohort study included all patients with >9 years of follow-up at a single high-volume epilepsy center. We included patients who underwent lobectomy, multilobar resection, or lesionectomies for drug-resistant epilepsy; we excluded patients who underwent hemispherectomies. Our main outcomes were (1) reduction in frequency of disabling seizures (at 6 months, each year up to 9 years postoperatively, and at last follow-up), (2) achievement of seizure remission (>6 months, >1 year, and longest duration), and (3) seizure freedom at last follow-up. RESULTS: We included 251 patients; 234 (93.2%) achieved 6 months and 232 (92.4%) experienced 1 year of seizure freedom. Of these, the average period of seizure freedom was 10.3 years. A total of 182 (72.5%) patients were seizure-free at last follow-up (defined as >1 year without seizures), with a median 11.9 years since remission. For patients not completely seizure-free, the mean seizure frequency reduction at each time point was 76.2%, and ranged from 66.6% to 85.0%. Patients decreased their number of antiseizure medications on average by .58, and 53 (21.2%) patients were on no antiseizure medication at last follow-up. Nearly half (47.1%) of those seizure-free at last follow-up were not seizure-free immediately postoperatively. SIGNIFICANCE: Patients who continue to have seizures after resection often have considerable reductions in seizure frequency, and many are able to achieve seizure freedom in a delayed manner.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: Performance of our algorithms on classifying seizure freedom was comparable to that of human reviewers (algorithm F1 = .88 vs. human annotator κ = .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. SIGNIFICANCE: 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.

Markov modelling of treatment response in a 30-year cohort study of newly diagnosed epilepsy.

People with epilepsy have variable and dynamic trajectories in response to antiseizure medications. Accurately modelling long-term treatment response will aid prognostication at the individual level and health resource planning at the societal level. Unfortunately, a robust model is lacking. We aimed to develop a Markov model to predict the probability of future seizure-freedom based on current seizure state and number of antiseizure medication regimens trialled. We included 1795 people with newly diagnosed epilepsy who attended a specialist clinic in Glasgow, Scotland, between July 1982 and October 2012. They were followed up until October 2014 or death. We developed a simple Markov model, based on current seizure state only, and a more detailed model, based on both current seizure state and number of antiseizure medication regimens trialled. Sensitivity analyses were performed for the regimen-based states model to examine the effect of regimen changes due to adverse effects. The model was externally validated in a separate cohort of 455 newly diagnosis epilepsy patients seen in Perth, Australia, between May 1999 and May 2016. Our models suggested that once seizure-freedom was achieved, it was likely to persist, regardless of the number of antiseizure medications trialled to reach that point. The likelihood of achieving long-term seizure-freedom was highest with the first antiseizure medication regimen, at approximately 50%. The chance of achieving seizure-freedom fell with subsequent regimens. Fluctuations between seizure-free and not seizure-free states were highest earlier on but decreased with chronicity of epilepsy. Seizure-freedom/recurrence risk tables were constructed with these probability data, similar to cardiovascular risk tables. Sensitivity analyses showed that the general trends and conclusions from the base model were maintained despite perturbing the model and input data with regimen changes due to adverse effects. Quantitative comparison with the external validation cohort showed excellent consistency at Year 1, good at Year 3 and moderate at Year 5. Quantitative models, as used in this study, can provide pertinent clinical insights that are not apparent from simple statistical analysis alone. Attaining seizure freedom at any time in a patient's epilepsy journey will confer durable benefit. Seizure-freedom risk tables may be used to individualize the prediction of future seizure control trajectory.

Clinical factors associated with late seizure remission after failed epilepsy surgery.

BACKGROUND: Some patients who initially fail epilepsy surgery later become seizure-free, but it is not clear how the clinical characteristics of the patients or post-operative modifications of anti-seizure medication (ASM) regimens contribute to late seizure remission. METHODS: We performed a retrospective chart review of patients undergoing epilepsy surgery at the University of Washington Regional Epilepsy Center between 2007 and 2017, including patients receiving neocortical resection, temporal lobectomy, and hippocampal laser interstitial therapy (LITT) ablation. We assessed seizure freedom, ASM changes, seizure frequency at the first and last follow-up, and type of lesion. Two-tailed Fisher's exact test and Mann-Whitney U test were used for statistical analyses. RESULTS: Two hundred and fifteen patients undergoing epilepsy surgery between 2007 and 2017 had both first and last follow-ups. Ninety-eight (46%) were not seizure-free at the first follow-up (mean 1.1 years post-operative). By the last follow-up (mean 4.7 years post-operative), 20% of those not initially seizure-free had become so. Those who were seizure-free at the last visit had lower median seizures per month in the first post-operative year (0.21 versus 0.95 per month in those not seizure-free, p < 0.001). There was also a significantly higher proportion of patients with cavernomas who were seizure-free at the last visit (25% vs. 1% of those not seizure-free at the last visit; p = 0.001), but no other differences in clinical characteristics. Of the 98 patients who had seizures at the first follow-up, 63% underwent post-operative modification of their ASM regimens. The rate of late seizure freedom was similar for patients with or without ASM changes: 21% were seizure-free at the last visit with ASM changes and 19% without ASM changes. There were no significant differences in which ASMs were changed between those who became seizure-free and those who did not, but patients who were subjected to further medical management were less likely to have had mesial temporal sclerosis (MTS) than those who were not. A number of patients not initially seizure-free who underwent ASM changes achieved seizure freedom as long as 10 years post-surgery. CONCLUSION: A substantial proportion of patients who initially fail epilepsy surgery will have late seizure remission. Those with cavernous hemangiomas were more likely to achieve late remission from seizures as were those with lower rates of seizures in the first year after surgery. The chances of achieving remission were similar in those with or without modification of their ASM regimens, but those with pre-operative MTS were more likely to achieve late seizure freedom without medication changes. At the individual level, patients may still achieve seizure freedom with ASM changes as long as ten years after the initial surgery.

Outcomes after laser interstitial thermal ablation for temporal lobe epilepsy: a systematic review and meta-analysis.

Epilepsy is a common condition that affects approximately 1% of the world's population, with about one-third being refractory epilepsy. Temporal lobe epilepsy is the most common type of drug-resistant epilepsy, and laser interstitial thermal therapy (LITT) is an innovative treatment. In this systematic review and meta-analysis, we aimed to summarize the current evidence on outcomes after LITT, including seizure freedom rate, complication rate, and neurocognitive outcome. PubMed and OVID Medline search engines were systematically searched for all indexed publications in the English language up to July15, 2023. The search was limited to human studies. Proportions and 95% confidence interval (CI) values were calculated for seizure, neurocognitive outcome, and complication rate. A total of 836 patients were included. Overall seizure outcomes, regardless of the pathology, included Engel I outcome in 56% (95% CI, 52.4-59.5%), Engel II outcome in 19.2% (95% CI, 15.4-23.6%), Engel III outcome in 17.3% (95% CI, 13.5-21.8%), and Engel IV outcome in 10.5% (95% CI 6.3-17%) of the patients. The overall decline in verbal and visual memory regardless of laterality was 24.2 (95% CI 8.6-52%) and 25.2% (8.3-55.8%). For naming, the decline was 13.4% (6.6-25.4%). The results of the pooled analysis in comparison with available data in the literature showed that seizure outcomes after LITT were slightly inferior to published data after temporal lobectomy. Data on cognitive outcomes after LITT are scarce and heterogeneous.

The clinical features of patients with seizure freedom and failure after total corpus callosotomy for childhood-onset refractory epilepsy.

BACKGROUND: Corpus callosotomy is a palliative surgery for medically refractory epilepsy. We aim to analyze the clinical features of patients with seizure freedom and failure after total corpus callosotomy for childhood-onset refractory epilepsy. METHODS: We retrospectively reviewed the clinical courses of patients with childhood-onset refractory epilepsy undergoing total corpus callosotomy between May 2009 and March 2019. Seizure outcome at the last follow-up was the primary outcome. The clinical features of patients with seizure freedom and failure after callosotomy were compared. RESULTS: Eighty patients with childhood-onset refractory epilepsy underwent total corpus callosotomy; 15 (18.8%) obtained freedom from all seizures and 19 (23.8%) had unworthwhile improvement and failure. The mean ages at seizure onset in patients with seizure freedom and failure after callosotomy were 5.7 and 5.9 years; and mean seizure durations were 9.4 and 11.5 years, respectively. Univariate analysis found epilepsy syndrome (p = 0.047), mental retardation (p = 0.007), previous medical history (p = 0.004), ≥10 seizures per day (p = 0.024), theta waves in the background electroencephalogram (p = 0.024), and acute postoperative seizure (p = 0.000) were associated with failure after callosotomy. Seizure freedom after callosotomy was more common among patients with less than 10 seizures per day. CONCLUSIONS: Total corpus callosotomy is an effective palliative procedure for childhood-onset refractory epilepsy, particularly for patients with specific clinical characteristics. Callosotomy has a high seizure-free rate in well-selected patients.

Development and validation of machine learning models for prediction of seizure outcome after pediatric epilepsy surgery.

OBJECTIVE: There is substantial variability in reported seizure outcome following pediatric epilepsy surgery, and lack of individualized predictive tools that could evaluate the probability of seizure freedom postsurgery. The aim of this study was to develop and validate a supervised machine learning (ML) model for predicting seizure freedom after pediatric epilepsy surgery. METHODS: This is a multicenter retrospective study of children who underwent epilepsy surgery at five pediatric epilepsy centers in North America. Clinical information, diagnostic investigations, and surgical characteristics were collected, and used as features to predict seizure-free outcome 1 year after surgery. The dataset was split randomly into 80% training and 20% testing data. Thirty-five combinations of five feature sets with seven ML classifiers were assessed on the training cohort using 10-fold cross-validation for model development. The performance of the optimal combination of ML classifier and feature set was evaluated in the testing cohort, and compared with logistic regression, a classical statistical approach. RESULTS: Of the 801 patients included, 61.3% were seizure-free 1 year postsurgery. During model development, the best combination was XGBoost ML algorithm with five features from the univariate feature set, including number of antiseizure medications, magnetic resonance imaging lesion, age at seizure onset, video-electroencephalography concordance, and surgery type, with a mean area under the curve (AUC) of .73 (95% confidence interval [CI] = .69-.77). The combination of XGBoost and univariate feature set was then evaluated on the testing cohort and achieved an AUC of .74 (95% CI = .66-.82; sensitivity = .87, 95% CI = .81-.94; specificity = .58, 95% CI = .47-.71). The XGBoost model outperformed the logistic regression model (AUC = .72, 95% CI = .63-.80; sensitivity = .72, 95% CI = .63-.82; specificity = .66, 95% CI = .53-.77) in the testing cohort (p = .005). SIGNIFICANCE: This study identified important features and validated an ML algorithm, XGBoost, for predicting the probability of seizure freedom after pediatric epilepsy surgery. Improved prognostication of epilepsy surgery is critical for presurgical counseling and will inform treatment decisions.

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures.

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32-56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy.

Quantifying and reporting outcome measures in pediatric epilepsy surgery: A systematic review.

Several instruments and outcomes measures have been reported in pediatric patients undergoing epilepsy surgery. The objective of this systematic review is to summarize, evaluate, and quantify outcome metrics for the surgical treatment of pediatric epilepsy that address seizure frequency, neuropsychological, and health-related quality of life (HRQL). We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify publications between 2010 and June 2021 from PubMed, Embase, and the Cochrane Database of Systematic Reviews that report clinical outcomes in pediatric epilepsy surgery. Eighty-one articles were included for review. Overall, rates of postoperative seizure frequency were the most common metric reported (n = 78 studies, 96%). Among the seizure frequency metrics, the Engel Epilepsy Surgery Outcome Scale (n = 48 studies, 59%) was most commonly reported. Neuropsychological outcomes, performed in 32 studies (40%) were assessed using 36 different named metrics. HRQL outcomes were performed in 16 studies (20%) using 13 different metrics. Forty-six studies (57%) reported postoperative changes in antiepileptic drug (AED) regimen, and time-to-event analysis was performed in 15 (19%) studies. Only 13 outcomes metrics (1/5 seizure frequency, 6/13 HRQL, 6/36 neuropsychological) have been validated for use in pediatric patients with epilepsy and only 13 have been assessed through reliability studies (4/5 seizure frequency, 6/13 HRQL, and 3/36 neuropsychological). Of the 81 included studies, 17 (21%) used at least one validated metric. Outcome variable metrics in pediatric epilepsy surgery are highly variable. Although nearly all studies report seizure frequency, there is considerable variation in reporting. HRQL and neuropsychological outcomes are less frequently and much more heterogeneously reported. Reliable and validated outcomes metrics should be used to increase standardization and accuracy of reporting outcomes in pediatric patients undergoing epilepsy surgery.

Long-term seizure and psychiatric outcomes following laser ablation of mesial temporal structures.

OBJECTIVE: Postsurgical seizure outcome following laser interstitial thermal therapy (LiTT) for the management of drug-resistant mesial temporal lobe epilepsy (MTLE) has been limited to 2 years. Furthermore, its impact on presurgical mood and anxiety disorders has not been investigated. The objectives of this study were (1) to identify seizure outcome changes over a period ranging from 18 to 81 months; (2) to investigate the seizure-free rate in the last follow-up year; (3) to identify the variables associated with seizure freedom; and (4) to identify the impact of LiTT on presurgical mood and anxiety disorders. METHODS: Medical records of all patients who underwent LiTT for MTLE from 2013 to 2019 at the University of Miami Comprehensive Epilepsy Center were retrospectively reviewed. Demographic, epilepsy-related, cognitive, psychiatric, and LiTT-related data were compared between seizure-free (Engel Class I) and non-seizure-free (Engel Class II + III + IV) patients. Statistical analyses included univariate and multivariate stepwise logistic regression analyses. RESULTS: Forty-eight patients (mean age = 43 ± 14.2 years, range = 21-78) were followed for a mean period of 50 ± 20.7 months (range = 18-81); 29 (60.4%) achieved an Engel Class I outcome, whereas 11 (22.9%) had one to three seizures/year. Seizure-freedom rate decreased from 77.8% to 50% among patients with 24- and >61-month follow-up periods, respectively. In the last follow-up year, 83% of all patients were seizure-free. Seizure freedom was associated with having mesial temporal sclerosis (MTS), no presurgical focal to bilateral tonic-clonic seizures, and no psychopathology in the last follow-up year. Presurgical mood and/or anxiety disorder were identified in 30 patients (62.5%) and remitted after LiTT in 19 (62%). SIGNIFICANCE: LiTT appears to be a safe and effective surgical option for treatment-resistant MTLE, particularly among patients with MTS. Remission of presurgical mood and anxiety disorders can also result from LiTT.

Lacosamide in monotherapy in BTRE (brain tumor-related epilepsy): results from an Italian multicenter retrospective study.

PURPOSE: Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. METHODS: We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). RESULTS: Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1-2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. CONCLUSIONS: This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

Seizure control in successive pregnancies in Australian women with epilepsy.

OBJECTIVES: To investigate control of epileptic seizures during pairs of successive pregnancies in antiseizure medication (ASM)-treated women with epilepsy. MATERIALS AND METHODS: Analysis of seizure freedom rates during 436 pairs of successive pregnancies in Australian women with epilepsy, in nearly all instances long-standing epilepsy. RESULT: There was a higher rate of seizure-free second pregnancies compared with first paired pregnancies (63.1% vs. 51.4%; Relative Risk (R.R.) = 1.2277; 95% CI 1.0930, 1.3789) and of seizure-free pre-pregnancy years before second as compared with first paired pregnancies in the same women (63.6% vs. 52.4%; R.R. = 1.2616; 95% CI 1.1337, 1.4040). In 108 women whose ASM therapy was unaltered throughout both of their pregnancies, the seizure-freedom rate was higher in the second of the paired pregnancies (82.4% vs. 69.4%; R.R. = 1.1867, 95% CI 1.0189, 1.3821). CONCLUSIONS: Altered ASM therapy after the first of a pair of successive pregnancies did not fully account for the better overall seizure control in the corresponding second pregnancies. Some additional factor may have been in operation, possibly a greater preparedness to undertake a further pregnancy if seizures were already fully controlled.

Epileptic seizure control during and after pregnancy in Australian women.

OBJECTIVES: To study factors that affected previous epileptic seizure control throughout pregnancy, during labour, and in the post-natal weeks. MATERIALS & METHODS: Analysis of data concerning seizure freedom that was available at various stages of 2337 pregnancies in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs, mainly employing multiple variable logistic regression techniques. RESULTS: Based on data available at the outset of pregnancy, the risk of seizure-affected that is, not seizure-free pregnancy was statistically significantly (p < .05) higher in pregnancies where there was previously uncontrolled epilepsy (78.1% vs. 20.8%) and focal epilepsy (51.3% vs. 39.7%), and decreased with later onset-age epilepsy (41.8% vs. 52.2% with onset before age 13 years), The risk did not differ between initially antiseizure medication (ASM)-treated or untreated pregnancies. For epilepsy receiving ASM therapy, 90.6% of 160 pregnancies of women with uncontrolled focal epilepsy that began before the age of 13 were seizure-affected. None of the above factors influenced the risk of seizures during labour, though having seizures during pregnancy increased the hazard (3.93 vs. 0.6%). Either ASM-treated pregnancy or labour being seizure-affected increased the risk of post-partum period seizures (33.0% vs. 6.67% for both stages being seizure-free). Use of particular ASMs had no statistically significant effect on the seizure control situation at any of the pregnancy stages studied. CONCLUSIONS: Obtaining full seizure control before pregnancy appeared to be the main factor in maintaining seizure freedom during pregnancy, labour and the post-natal weeks.

Sustained seizure freedom with adjunctive perampanel in patients with convulsive seizures: Post hoc analysis of open-label extension studies 307 and 332.

OBJECTIVE: Since increased mortality rates have been associated with convulsive seizures, it is important to achieve seizure control in these patients. Here, we report post hoc analyses to assess long-term seizure-freedom rates with adjunctive perampanel in patients (aged ≥ 12 years) with refractory focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS) who participated in open-label extension (OLEx) studies. METHODS: Patients with focal-onset seizures, with/without FBTCS, who completed double-blind, Phase III Studies 304, 305, or 306 could enter OLEx Study 307 (16-week blinded Conversion; 256-week Maintenance). Patients with GTCS who completed the double-blind phase of Study 332 could enter the OLEx Phase (6-week blinded Conversion; 136-week Maintenance). Maximum perampanel dose: 12 mg/day. Seizure-freedom rates for up to 24 months were assessed in perampanel-treated patients who achieved seizure freedom during the double-blind studies to determine if their seizure-free status was maintained during the OLEx. In addition, to ensure any patients who only achieved seizure freedom during the OLEx were captured, seizure-freedom rates were also assessed in all patients who achieved and maintained a seizure-free status for a period of at least six consecutive months at any time during the double-blind and/or OLEx studies; some of these patients may have received placebo during the double-blind study but only their time on perampanel is included in the seizure-free analysis. Univariate and multivariate analyses were used to identify predictive factors for achieving seizure freedom for at least 6 months. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Overall, 53.8% (n = 42/78) of patients who received perampanel and were FBTCS free during the double-blind studies remained seizure free for up to 24 months during Study 307, and 31.6% (n = 6/19) of patients who were GTCS free during the double-blind phase of Study 332 remained seizure free for up to 24 months during the OLEx Phase. Over 40% (FBTCS, 41.5% [n = 197/475]; GTCS, 52.9% [n = 73/138]) of patients were seizure free for a period of at least six consecutive months. Multivariate analysis showed that the best predictors of achieving seizure freedom from FBTCS for at least 6 months were lower baseline seizure frequency (p = 0.0014) and absence of enzyme-inducing anti-seizure medications at baseline (p = 0.0056); multivariate analysis was not conducted for GTCS since only one variable was identified as a significant predictor of seizure freedom in the univariate analysis (lower baseline seizure frequency). Perampanel was generally well tolerated with no new safety signals identified. The most common TEAE was dizziness. For both seizure types, 10% or fewer seizure-free patients discontinued perampanel due to TEAEs. CONCLUSIONS: These results suggest that adjunctive perampanel may be a suitable long-term treatment option for patients (aged ≥ 12 years) with convulsive seizures to achieve and maintain seizure freedom.

Rapid versus slow withdrawal of antiepileptic monotherapy in two-year seizure-free adults patients with epilepsy (RASLOW) study: A pragmatic multicentre, prospective, randomized, controlled study.

PURPOSE: To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death. METHODS: This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2 years. Patients were randomized to slow withdrawal (160 days) or rapid withdrawal (60 days) and were followed for 12 months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12 months. A non-inferiority analysis was performed with non-inferiority margin of - 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal. RESULTS: The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9 months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI - 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population. CONCLUSIONS: Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering.