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.

Quality of life before and after epilepsy surgery: Age is just a number.

BACKGROUND: In a rapidly aging population, it is critical to analyze if the quality of life (QOL) in patients with drug-resistant epilepsy (DRE) and the change in it after epilepsy surgery is dependent on the age at operation. METHODS: A prospective registry-based retrospective cohort study including adults with a completed pre- and post-surgery Quality of Life in Epilepsy 10 (QOLIE-10) survey. Multivariable linear regression models analyzed the baseline, postoperative, or change in QOLIE-10 score. RESULTS: We analyzed 416 patients (51% females) with the mean age of 39.6 (SD = 12.6) years at the time of surgery, including 100 (24%) individuals 50 years or older. The younger and older adults (dichotomized as <50 vs. ≥50 and <60 vs. ≥60) had comparable pre- and post-surgery QOLIE 10 total scores. The change in total and individual QOLIE-10 items score were comparable between the groups as well. Within group improvements in total QOLIE-10 score post-surgery was in younger as well as older groups. The linear regression models showed that age, regardless of parameterization (linear or dichotomized), was not related to pre-surgery, post-surgery, and change in QOLIE-10 score, both before and after adjustment for covariates. The change in QOLIE-10 score did not show correlation with age, whether seizure freedom or relative seizure reduction was used in the model. CONCLUSION: With QOL, before or after surgery, being independent of a patient's age, our findings suggest that well-selected older adults and the elderly should be offered epilepsy surgery without concern for an inferior improvement in QOL compared to their younger counterparts.

Cost-effectiveness of surgery for drug-resistant temporal lobe epilepsy in the US.

OBJECTIVE: Surgery is an effective but costly treatment for many patients with drug-resistant temporal lobe epilepsy (DR-TLE). We aim to evaluate whether, in the United States, surgery is cost-effective compared to medical management for patients deemed surgical candidates and whether surgical evaluation is cost-effective for patients with DR-TLE in general. METHODS: We use a semi-Markov model to assess the cost-effectiveness of surgery and surgical evaluation over a lifetime horizon. We use second-order Monte Carlo simulations to conduct probabilistic sensitivity analyses to estimate variation in model output. We adopt both health care and societal perspectives, including direct health care costs (e.g., surgery, antiepileptic drugs) and indirect costs (e.g., lost earnings by patients and care providers.) We compare the incremental cost-effectiveness ratio to societal willingness to pay (∼$100,000 per quality-adjusted life-year [QALY]) to determine whether surgery is cost-effective. RESULTS: Epilepsy surgery is cost-effective compared to medical management in surgically eligible patients by virtue of being cost-saving ($328,000 vs $423,000) and more effective (16.6 vs 13.6 QALY) than medical management in the long run. Surgical evaluation is cost-effective in patients with DR-TLE even if the probability of being deemed a surgical candidate is only 5%. From a societal perspective, surgery becomes cost-effective within 3 years, and 89% of simulations favor surgery over the lifetime horizon. CONCLUSION: For surgically eligible patients with DR-TLE, surgery is cost-effective. For patients with DR-TLE in general, referral for surgical evaluation (and possible subsequent surgery) is cost-effective. Patients with DR-TLE should be referred for surgical evaluation without hesitation on cost-effectiveness grounds.

Quantifying the burden of generalized tonic-clonic seizures in patients with drug-resistant epilepsy.

OBJECTIVE: Compared to other seizure types, generalized tonic-clonic (GTC) seizures may be disproportionately related to increased morbidity, and reducing seizure frequency could translate into improvements across measures of morbidity in medically treated patients with drug-resistant epilepsy (DRE). The primary objective of this analysis was to quantify the burden of patients with DRE who experience GTC seizures (GTC+) compared to patients with DRE who do not experience GTC seizures (GTC-). METHODS: Adult patients from the Cleveland Clinic Epilepsy Center-Neurological Institute from 2012-2016 with DRE with epilepsy for at least 1 year were eligible for inclusion and were divided into GTC ± groups based on whether the patient had experienced a GTC seizure in the year preceding the first visit. Epilepsy duration, comorbidities, antiepileptic drug use, patient-reported outcomes (PROs) and seizure type, frequency, and etiology were captured. Generalized linear models, negative binomial regression, logistic regression, and linear regression were used as appropriate for multivariate analyses. RESULTS: A total of 379 patients met inclusion criteria and had data at 1-year follow-up after their baseline visit (192 GTC+ and 187 GTC-). Although DRE patients experiencing GTC seizures had fewer seizures per day over the preceding 6 months than those not experiencing GTC seizures, seizure severity and levels of depression and anxiety were greater. GTC+ patients who reported five or more seizures in the preceding 4 weeks had 82% lower odds (1-0.18 = 0.82) of working than patients with no seizures. SIGNIFICANCE: Patients with DRE experience a significant burden and decreased quality of life. Multivariate analysis is necessary to understand the complex relationship between seizure type, frequency, and impact on health-related quality of life (HRQoL) and changes over time. Effective treatments to reduce the burden for DRE patients who experience GTC seizures continue to be needed.

Tracking a changing paradigm and the modern face of epilepsy surgery: A comprehensive and critical review on the hunt for the optimal extent of resection in mesial temporal lobe epilepsy.

Surgical management of medically intractable epilepsy was historically based on the premise of excising the presumed substrate of disease, that is, "the epileptogenic zone." There was early interest in establishing the extent of resection of the temporal lobe that optimized postoperative reduction in seizure burden while preserving neurocognitive function. Studies approaching this question used varied methods of defining and measuring "extent," complicating the task of distilling evidence-based recommendations for surgical practice. A palpable shift in the paradigm of surgical epilepsy has gained traction and greatly altered not only the kind of studies being undertaken but the focus of inquiry itself. Key to this paradigm shift has been the increasingly well-held notion that epilepsy, far from being a disease of a single problem focus, is rather a disease of a problem network. Where a former generation of investigators labored to find an optimal extent of resection, concentrating on magnetic resonance imaging-visible lesions and on standardization of the extent of resection (ie, "standard temporal lobectomy"), the modern strategy is more concerned with understanding network activation and its concordance with presurgical clinical and electrophysiological features and the organization of epileptic activity over time. The vital lessons of the early literature investigating optimal extent of resection, however, remain informative to the field, and it is worthwhile to contextualize them within the modern network-focused paradigm. In this comprehensive review of the literature, we aim to recapitulate the major findings of the "optimal extent of resection" literature (focusing on both seizure control and neuropsychological outcomes) and distill wherever possible the consensus findings that may guide surgical approach to epileptic disease of the temporal lobe. We also review the particular implications of modern laser ablation techniques on the question of "optimal extent of resection" in temporal lobe epilepsy, and contextualize them as a marker of a shifting paradigm.