Predictive models of epilepsy outcomes.

PURPOSE OF REVIEW: Multiple complex medical decisions are necessary in the course of a chronic disease like epilepsy. Predictive tools to assist physicians and patients in navigating this complexity have emerged as a necessity and are summarized in this review. RECENT FINDINGS: Nomograms and online risk calculators are user-friendly and offer individualized predictions for outcomes ranging from safety of antiseizure medication withdrawal (accuracy 65-73%) to seizure-freedom, naming, mood, and language outcomes of resective epilepsy surgery (accuracy 72-81%). Improving their predictive performance is limited by the nomograms' inability to ingest complex data inputs. Conversely, machine learning offers the potential of multimodal and expansive model inputs achieving human-expert level accuracy in automated scalp electroencephalogram (EEG) interpretation but lagging in predictive performance or requiring validation for other applications. SUMMARY: Good to excellent predictive models are now available to guide medical and surgical epilepsy decision-making with nomograms offering individualized predictions and user-friendly tools, and machine learning approaches offering the potential of improved performance. Future research is necessary to bridge the two approaches for optimal translation to clinical care.

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.

Comparative Effectiveness of Stereotactic Electroencephalography Versus Subdural Grids in Epilepsy Surgery.

OBJECTIVE: The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography (iEEG) performed in difficult-to-localize drug-resistant focal epilepsy. METHODS: The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit). RESULTS: Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE). INTERPRETATION: In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939.

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.

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.

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.

(Re)Defining success in epilepsy surgery: The importance of relative seizure reduction in patient-reported quality of life.

OBJECTIVE: Previous work has suggested that seizure outcome is the most important predictor of quality of life (QoL) after epilepsy surgery, but it is unknown which specific seizure outcome measure should be used in judging surgical success. We assess three different seizure outcome measures (relative seizure reduction, absolute seizure reduction, and seizure freedom [yes/no]) to investigate which measure best predicts postoperative QoL. METHODS: We prospectively surveyed patients at outpatient visits before and after epilepsy surgery (n = 550). The QoL measure was the Quality of Life in Epilepsy (QOLIE-10) score at the patient's most recent office visit. We created multivariate regression models to predict postoperative QOLIE-10, with a different seizure outcome measure in each model. We compared models using adjusted R2 values and Akaike information criteria (AIC). RESULTS: Our cohort had a high level of disease severity and complexity (17% repeat surgery, 39% extratemporal, and 18% nonlesional). For the cohort as a whole, mean absolute seizure frequency decreased from 1 per day to 0.1 per day (P < .001), and mean reduction was 73% (95% confidence interval [CI] 66%-81%). Average improvement in QoL score was 5.3 (95% CI 4.1-6.5) points. Of patients who reported an improvement in QoL, 27% had persistent seizures. Comparison of regression models to predict QoL showed that the worst model was provided when using "absolute seizure reduction," but that models using "relative seizure reduction" and "seizure freedom (yes/no)" were equally strong. SIGNIFICANCE: In our high severity and complexity cohort, a substantial subset of patients (27%) reported improved QoL despite persistent seizures. Relative seizure reduction was at least as good a predictor of QoL as seizure freedom. A yes/no seizure freedom variable may be a suboptimal measure of surgical success, especially in high complexity cohorts.

Prevalence of Pediatric Cataract in Asia: A Systematic Review and Meta-Analysis.

Purpose: To conduct a systematic review and meta-analysis for estimating the prevalence of pediatric cataracts across Asia. Methods: A detailed literature search of PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases, from 1990 to July 2021, was performed to include all studies reporting the prevalence of cataracts among children. Two researchers performed the literature search and screening of articles independently, and a third researcher critically reviewed the overall search and screening process to ensure the consistency. The JBI Critical Appraisal Checklist for studies reporting prevalence data was used to assess the methodological quality of the included studies. Results: Of the 496 identified articles, 35 studies with a sample size of 1,168,814 from 12 Asian countries were included in this analysis. The estimated pooled prevalence of pediatric cataracts in Asian children is 3.78 (95% confidence interval: 2.54-5.26)/10,000 individuals with high heterogeneity (I[2] = 89.5%). The pooled prevalence by each country per 10,000 was 0.60 in Indonesia, 0.92 in Bangladesh, 1.47 in Iran, 2.01 in Bhutan, 3.45 in Laos, 3.68 in China, 4.27 in Thailand, 4.47 in India, 5.33 in Malaysia, 5.42 in Nepal, 9.34 in Vietnam, and 10.86 in Cambodia. Conclusions: This study utilizes existing literature to identify the prevalence of cataracts in Asian children. Moreover, it highlights the need for more epidemiological studies with large sample sizes from other countries in Asia to accurately estimate the burden of disease.

Imaging Technologies in Spine Surgery.

This article presents a comprehensive review of the evolution of both invasive and noninvasive imaging technologies that are part of the arsenal of spinal diagnostics and surgical therapy. The text provides not only a historical lens to the evolution of the imaging technologies that are part of routine contemporary practice but also provides a detailed sketch of emerging imaging technologies, such as endoscopic and exoscopic systems. Augmented reality, virtual reality, and mixed reality are new technologies that have enhanced the preparation of surgery and provide excellent case-specific training modules to break down each step of an operation in isolation.

Long-term trends in glioblastoma survival: implications for historical control groups in clinical trials.

BACKGROUND: Historical controls continue to be used in early-phase brain tumor trials. We aim to show that historical changes in survival trends for glioblastoma (GBM) call into question the use of noncontemporary controls. METHODS: We analyzed data from 46 106 primary GBM cases from the SEER database (1998-2016). We performed trend analysis on survival outcomes (2-year survival probability, median survival, and hazard ratios) and patient characteristics (age, sex, resection extent, and treatment type). RESULTS: In 2005-2016 (ie, the post-Stupp protocol era), fitting a parameter independently to each year, there was a demonstrable increase in median survival (R2 = 0.81, P < .001) and 2-year survival probability (R2 = 0.55, P = .006) for GBM. Trend analysis of the hazard ratio showed a significant time-dependent downward trend (R2 = 0.62, P = .002). When controlling, via multivariable Cox regression modeling, for age, sex, resection extent, and treatment type, there was a persistent downward trend in hazard ratios with increases in calendar time, especially in the most recent data. CONCLUSION: Contemporary GBM patients face a different overall hazard profile from their historical counterparts, which is evident in changes in measures of patient survival and parametric hazard modeling. Though there was a plateau in these measures before 2005 (pre-Stupp protocol), there is no evidence of a new plateau in recent years even when controlling for known prognostic factors (age, sex, resection extent, and treatment type), suggesting that it may be insufficient to match contemporary patients and noncontemporary controls on the basis of these factors.

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.

Can We Justify It? Trends in the Utilization of Spinal Fusions and Associated Reimbursement.

BACKGROUND: Previous reports have suggested an increasing rate of utilization of spinal fusions, but contemporary data have not been analyzed, and there has been little investigation of putative drivers of increased utilization. OBJECTIVE: To investigate whether there is an ongoing trend of increased utilization of spinal fusions in recent data, and if there may be associations with an increasing proportion of elderly in the population, changing patterns of payer-types, and changing reimbursement rates. METHODS: We analyze 7.1 million cases from the National Inpatient Sample between 1998 and 2014. We measure annual utilization per 100 000 persons and conduct trend analyses with subgroup analysis of the senior (65 + ) population. Spine surgery utilization is compared with nonspine surgical procedures (coronary artery bypass grafting, hernia repair, hip, and knee replacement). We assess trends in charges, payer type, Medicare reimbursement rates, and hospital type. RESULTS: There was an 88% increase in the utilization rate of spinal fusion procedures from 1998 to 2014 (from 74 to 139 cases per 100 000 persons) with a significant upward trend (P < .001) that persisted in the 65 + subgroup (P < .001). An increasing proportion of spinal fusions is paid for by public payers, but per-procedure reimbursement for spinal fusions by Medicare has decreased recently (5% reduction from 2014 to 2016). CONCLUSION: Utilization of spinal fusions continues to increase and is not explained by increased proportion of elderly in the population, increased utilization of surgeries across specialties, or increased Medicare reimbursement. In fact, increased utilization of spinal fusions temporally correlated with decreasing per-procedure Medicare reimbursement.