Rates and predictors of success and failure in repeat epilepsy surgery: A meta‐analysis and systematic review

Abstract

Summary Objective Medically refractory epilepsy is a debilitating disorder that is particularly challenging to treat in patients who have already failed a surgical resection. Evidence regarding outcomes of further epilepsy surgery is limited to small case series and reviews. Therefore, our group performed the first quantitative meta-analysis of the literature from the past 30 years to assess for rates and predictors of successful reoperations. Methods A PubMed search was conducted for studies reporting outcomes of repeat epilepsy surgery. Studies were excluded if they reported fewer than 5 eligible patients or had average follow ups < 1 year, and patients were excluded from analysis if they received a non-resective intervention. Outcomes were stratified by each variable of interest and quantitative meta-analysis was performed to generate odds ratios (OR) and 95% confidence intervals (CI). Results 782 patients who received repeat resective epilepsy surgery from 36 studies were included. Engel I outcome was observed in 47% (N=369) of patients. Significant predictors of seizure freedom in included congruent over non-congruent electrophysiology data (OR 3.6, 95% CI 1.6–8.2), lesional over non-lesional epilepsy (OR 3.2, 95% CI 1.9–5.3), and surgical limitations over disease-related factors associated with failure of the first surgery (OR 2.6, 95% CI 1.3–5.3). Among patients with at least one of these predictors, seizure freedom was achieved in 58%. Conversely, the use of invasive monitoring was associated with worse outcome (OR 0.4, 95% CI 0.2–0.9). Temporal lobe over extratemporal/multilobe resection (OR 1.5, 95% CI 0.8–3.0) and abnormal over normal pre-operative MRI (OR 1.9, 95% CI 0.6–5.4) showed non-significant trends toward seizure freedom. Significance This analysis supports considering further resection in patients with intractable epilepsy who continue to have debilitating seizures after an initial surgery, especially in the context of factors predictive of a favorable outcome.

Long‐term outcomes of reoperations in epilepsy surgery

“…This is a complex and difficult to treat patient population, and little literature is available to guide the selection of patients for reoperations. The meta‐analysis by Krucoff et al effectively shed light on outcomes in patients with a single reoperation; however, the effect of consecutive reoperations was not addressed. Additionally, it had the inherent disadvantage of heterogeneity that a meta‐analysis carries, as the compilation included studies from several countries with variations in diagnostic, explorative, and resective techniques.…”

“…The poor outcome predictors in the cohort with multiple surgeries were more closely correlated with inherent biological characteristics (sex and tendency for secondary generalization—the only variables that retained significance after multivariate analysis) rather than with poorly localized epilepsy. This suggests that at least some of the patients who continue to have seizures despite multiple reoperations may be “surgically refractory.” They have a widespread, “malignant” epileptogenic network with a tendency to develop new epileptogenic zones, on resection of the prior zone, causing a progressive disease state that may be “surgically refractory.” It may reasonably be argued that such patients are inappropriate surgical candidates at the time of first surgery. However, the concept of a poor surgical candidate is still nebulous, and considering the limitations of our cohort size, future research may help in better delineation of such patients while refining the identification of ideal candidates.…”

“…6,7 This is a particular challenge considering that data on long-term outcomes and their predictors after reoperations are limited. As highlighted in a recent comprehensive meta-analysis of the heterogeneous available literature, 8 most studies were underpowered, not controlled, and some were restricted to a specific age group, 6 a specific pathology, 9 or a specific lobe. [10][11][12][13] In addition, all published experience is limited to a single reoperation, limiting its applicability in patients requiring multiple reoperations.…”

Outcomes of stereoelectroencephalography exploration at an epilepsy surgery center

“…Even though some authors suggest that use of IVEM during first surgery could increase the likelihood of a successful reoperation, 26 a recent meta-analysis showed otherwise. 27 Reoperation still remains a feasible option for seizure freedom in these surgical failures. Comparison with previous SEEG studies is available as Table S2.…”

Fast oscillations >40Hz localize the epileptogenic zone: an electrical source imaging study using high-density electroencephalography

“…In current praxis, the seizure-onset zone (SOZ) is used as the main proxy marker for the EZ. A sustained seizure-free condition is currently, however, obtained in only 50% of carefully selected patients [Krucoff et al, 2017; Mohan et al, 2018; West et al, 2019]. This is likely due to inaccurate localization of the EZ or a network involvement larger than initially expected [Englot, 2018].…”