Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults.

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7-11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9-2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8-0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9-1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63-0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64-0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative antiseizure medication withdrawal. These multicentre-validated models may assist clinicians when discussing antiseizure medication withdrawal after surgery with their patients.

Telemedicine as a path to bridging inequities in patients with epilepsy.

OBJECTIVE: Access to epilepsy specialist care is not uniform in the USA, with prominent gaps in rural areas. Understanding the reasons for nonattendance at epilepsy appointments may help identify access hurdles faced by patients. This study was undertaken to better understand clinic absenteeism in epilepsy and how it may be influenced by telemedicine. METHODS: In this retrospective study, social determinants of health were collected for all adult patients scheduled in epilepsy clinic, as either an in-person or telemedicine appointment, at University of Kentucky between July 2021 and December 2022. The primary outcome measure was attendance or absence at the appointment. Subgroup analyses were done to better understand the drivers of attendance at telemedicine visits and evaluate telemedicine utilization by underserved populations. RESULTS: A total of 3025 patient encounters of in-person and telemedicine visits were included. The no-show rate was significantly higher for in-person visits (32%) compared with telemedicine visits (20%, p < .001). A nominal logistic regression model identified seven factors increasing risk of absenteeism, including in-person visits, prior missed appointments, longer lead times to appointment, Medicaid/Medicare as payors, no significant other, lower mean annual income, and minority race. For each $10 000 increase in mean annual income, the odds of missing the appointment decreased by 8% (odds ratio = .92, 95% confidence interval = .89-.96, p < .001). Forty-one percent of underserved population opted for telemedicine visits, and they had a lower no-show rate (22%) as compared with in-person visits (33%, p < .001). Predictors of no-shows to televisits (1382) included Medicare/Medicaid coverage (as opposed to private insurance), no significant others, and a history of missing appointments. SIGNIFICANCE: Telemedicine is effective at improving attendance, overcoming socioeconomic hurdles, and widening access to epilepsy care, particularly among underserved populations. Access to telecare depends on insurance coverage and emphasizes the need to include telemedicine in insurance plans to ensure uniform access to high-quality epilepsy care, irrespective of socioeconomic status.

Long-term outcomes of reoperations in epilepsy surgery.

OBJECTIVE: To analyze longitudinal seizure outcomes following epilepsy surgery, including reoperations, in patients with intractable focal epilepsy. METHODS: Clinicoradiological characteristics of patients who underwent epilepsy surgery from 1995 to 2016 with follow-up of ≥1 year were reviewed. In patients undergoing reoperations, the latest resection was considered the index surgery. The primary outcome was complete seizure freedom (Engel I) at last follow-up. Potentially significant outcome variables were first identified using univariate analyses and then fit in multivariate Cox proportional hazards models. RESULTS: Of 898 patients fulfilling study criteria, 110 had reoperations; 92 had one resection prior to the index surgery and 18 patients had two or more prior resective surgeries. Two years after the index surgery, 69% of patients with no prior surgeries had an Engel score of I, as opposed to only 42% of those with one prior surgery, and 33% of those with two or more prior resections (P < .001). Among surgical outcome predictors, the number of prior epilepsy surgeries, female sex, lesional initial magnetic resonance imaging, no prior history of generalization, and pathology correlated with better seizure outcomes on univariate analysis. However, only sex (P = .011), history of generalization (P = .016), and number of prior surgeries (P = .002) remained statistically significant in the multivariate model. SIGNIFICANCE: Although long-term seizure control is possible in patients with failed prior epilepsy surgery, the chances of success diminish with every subsequent resection. Outcome is additionally determined by inherent biological markers (sex and secondary generalization tendency), rather than traditional outcome predictors, supporting a hypothesis of "surgical refractoriness."

The relevance of somatosensory auras in refractory temporal lobe epilepsies.

The purpose of this study is to look at the prevalence, characteristics, and prognostic value of somatosensory auras (SSAs) in patients who have undergone temporal lobe epilepsy (TLE) surgery to treat drug-resistant focal epilepsy. We retrospectively reviewed all patients with drug-resistant epilepsy who underwent TLE surgery at Cleveland Clinic between 2005 and 2010 (n = 333) to study the prevalence, characteristics, and prognostic implications of SSA in the context of TLE surgery. Analyses were performed using two seizure outcome definitions: complete seizure freedom and Engel classification. Of the 333 patients, 26 (7.8%) had SSA. Almost half (12 patients) had unilateral sensory symptoms, whereas the rest had bilateral symptoms. Tingling and numbness were the most frequently reported sensations. Compared to their non-SSA counterparts, patients with SSA had the same clinical and imaging characteristics, but had a higher rate of breakthrough seizures (p = 0.03), although most (54%) were still able to achieve Engel class of I (p = 0.02). Based on our results we would encourage detailed presurgical testing, which may include an invasive evaluation to analyze the extent of the epileptogenic zone in patients with SSA and suspected TLE.

Seizure freedom score: a new simple method to predict success of epilepsy surgery.

OBJECTIVE: We aim to develop a new scale that predicts seizure outcomes after resective epilepsy surgery. METHODS: We retrospectively reviewed patients who underwent surgery for medically refractory epilepsy at our center between 1999 and 2012. Four predictive outcome indicators were selected: preoperative seizure frequency, history of generalized tonic-clonic seizures, brain magnetic resonance imaging (MRI), and epilepsy duration. A score of 0 or 1 was given if the indicator was associated with poor or good outcome, respectively. A seizure freedom score (SFS) was calculated by adding these four categories (total score ranged from 0 to 4). A modified SFS (m-SFS) was then calculated with two additional outcome indicators: invasive electroencephalography (EEG) evaluation (IEI) (performed or not performed) and lobe of resection (temporal vs. extratemporal), for a score ranging from 0 to 6. Kaplan-Meier survival analysis was used to calculate the probability of seizure freedom in the overall group. Statistical significance was tested using the log-rank test and comparison of 95% confidence intervals (CIs). RESULTS: The study population included 466 patients with 244 (52%) male. Seizure freedom rates were directly correlated with the SFS score: at 10 years, 36.9% of patients with SFS of 0 were seizure-free, as opposed to 45% for SFS = 1, 60% for SFS = 2, 72% for SFS 3 or above (p = 0.002). When calculated including the IEI and the localization, the score's performance improved: 24% of patients with a m-SFS of 0 were seizure-free at 10 years, as opposed to 38-59% for m-SFS = 1-3, and 75-79% for m-SFS of 4-6 (p < 0.001). SIGNIFICANCE: An easily measurable seizure freedom score could be a reliable tool to synthesize multiple seizure outcome predictors into a single simple score to predict postoperative seizure freedom. This tool will help with patient and family counseling and estimation of surgical candidacy at both early (SFS) and advanced (m-SFS) stages of a surgical evaluation.

Effect of invasive EEG monitoring on cognitive outcome after left temporal lobe epilepsy surgery.

OBJECTIVES: The objective of this cohort study was to compare neuropsychological outcomes following left temporal lobe resection (TLR) in patients with epilepsy who had or had not undergone prior invasive monitoring. METHODS: Data were obtained from an institutional review board-approved, neuropsychology registry for patients who underwent epilepsy surgery at Cleveland Clinic between 1997 and 2013. A total of 176 patients (45 with and 131 without invasive EEG) met inclusion criteria. Primary outcome measures were verbal memory and language scores. Other cognitive outcomes were also examined. Outcomes were assessed using difference in scores from before to after surgery and by presence/absence of clinically meaningful decline using reliable change indices (RCIs). Effect of invasive EEG on cognitive outcomes was estimated using weighting and propensity score adjustment to account for differences in baseline characteristics. Linear and logistic regression models compared surgical groups on all cognitive outcomes. RESULTS: Patients with invasive monitoring showed greater declines in confrontation naming; however, when RCIs were used to assess clinically meaningful change, there was no significant treatment effect on naming performance. No difference in verbal memory was observed, regardless of how the outcome was measured. In secondary outcomes, patients with invasive monitoring showed greater declines in working memory, which were no longer apparent using RCIs to define change. There were no outcome differences on other cognitive measures. CONCLUSIONS: Results suggest that invasive EEG monitoring conducted prior to left TLR is not associated with greater cognitive morbidity than left TLR alone. This information is important when counseling patients regarding cognitive risks associated with this elective surgery.

Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis.

BACKGROUND: Half of patients who have resective brain surgery for drug-resistant epilepsy have recurrent postoperative seizures. Although several single predictors of seizure outcome have been identified, no validated method incorporates a patient's complex clinical characteristics into an instrument to predict an individual's post-surgery seizure outcome. METHODS: We developed nomograms to predict complete freedom from seizures and Engel score of 1 (eventual freedom from seizures allowing for some initial postoperative seizures, or seizures occurring only with physiological stress such as drug withdrawal) at 2 years and 5 years after surgery on the basis of sex, seizure frequency, secondary seizure generalisation, type of surgery, pathological cause, age at epilepsy onset, age at surgery, epilepsy duration at time of surgery, and surgical side. We designed the models from a development cohort of patients who had resective surgery at the Cleveland Clinic (Cleveland, OH, USA) between 1996 and 2011. We then tested the nomograms in an external validation cohort operated on over a similar period in four epilepsy surgery centres, in Brazil, France, Italy, and the USA. We assessed performance of the nomogram by calculating concordance statistics and assessing the calibration of predicted freedom from seizures with the reported freedom from seizures and Engel score of 1. FINDINGS: The development cohort included 846 patients and the validation cohort included 604 patients. Variables included in the nomograms were sex, seizure frequency, secondary seizure generalisation, type of surgery, and pathological cause. In the development cohort, the baseline risk of complete freedom from seizures was 0·57 at 2 years and 0·40 at 5 years. The baseline risk of Engel score of 1 was 0·69 at 2 years and 0·62 at 5 years. In the validation cohort, the models had a concordance statistic of 0·60 for complete freedom from seizures and 0·61 for Engel score of 1. Calibration curves showed adequate calibration (judged by eye) of predicted and reported freedom from seizures, throughout the range of seizure outcomes. INTERPRETATION: If validated in prospective cohorts, these nomograms could be used to predict seizure outcomes in patients who have been judged eligible for epilepsy surgery. FUNDING: Cleveland Clinic Epilepsy Center.

Reducing versus stopping antiepileptic medications after temporal lobe surgery.

OBJECTIVE: To study the safety of antiepileptic drug (AED) withdrawal after temporal lobe epilepsy (TLE) surgery. METHODS: We reviewed patients who underwent TLE surgery from 1995 to 2011, collecting data on doses, dates of AED initiation, reduction, and discontinuation. Predictors of seizure outcome were defined using Cox-proportional hazard modeling and adjusted for, while comparing longitudinal seizure-freedom in patients for whom AEDs were unchanged after resection as opposed to reduced or stopped. RESULTS: A total of 609 patients (86% adults) were analyzed. Follow-up ranged from 0.5 to 16.7 years. Most (64%) had hippocampal sclerosis. Overall, 229 patients had remained on their same baseline AEDs, while 380 patients stopped (127 cases) or reduced (253 cases) their AEDs. Mean timing of the earliest AED change was shorter in patients with recurrent seizures (1.04 years) compared to those seizure-free at last follow-up (1.44 years; P-value 0.03). Whether AEDs were withdrawn 12 or 24 months after surgery, there was a 10-25% higher risk of breakthrough seizures within the subsequent 2 years. However, 70% of patients with seizure recurrence after AED discontinuation reachieved remission, as opposed to 50% of those whose seizures recurred while reducing AEDs (P = 0.0001). Long-term remission rates were similar in both AED discontinuation and "unchanged" groups (82% remission for AEDs withdrawn after 1 year and 90% for AEDs withdrawn after 2 years), while only 65% of patients whose recurrences started during AED reduction achieved a 2-year remission by last follow-up. INTERPRETATION: AED withdrawal increases the short-term risk of breakthrough seizures after TLE surgery, and may alter the long-term disease course in some patients.