Association of Seizure Spread With Surgical Failure in Epilepsy

Abstract

IMPORTANCE Seizures recur in as many as half of patients who undergo surgery for drug-resistant temporal lobe epilepsy (TLE). Understanding why TLE is resistant to surgery in some patients may reveal insights into epileptogenic networks and direct new therapies to improve outcomes. OBJECTIVE To characterize features of surgically refractory TLE. DESIGN, SETTING, AND PARTICIPANTS Medical records from a comprehensive epilepsy center were retrospectively reviewed for 131 patients who received a standard anteromedial temporal resection by a single surgeon from January 1, 2000, to December 31, 2015. Thirteen patients were excluded for having less than 1 year of follow-up. Patients at the highest risk for seizure recurrence were identified. Intracranial electroencephalogram (iEEG) analyses generated 3-dimensional seizure spread representations and quantified rapid seizure spread. The final analyses of seizure outcome and follow-up data were performed in June 2017. MAIN OUTCOMES AND MEASURES The Engel class seizure outcome following surgery was evaluated for all patients, defining seizure recurrence as Engel class II or greater. Intracranial recordings of neocortical grids/strips and depth electrodes were analyzed visually for seizure spread. Fast β power was projected onto reconstructions of patients' brain magnetic resonance imaging scans to visualize spread patterns and was quantified to compare power within vs outside resective margins. RESULTS Of 118 patients with 1 year of follow-up or more (mean [SD], 6.5 [4.6] years), 66 (55.9%) were women and 52 (44.1%) were men (median age, 39 years [range, 4-66 years]). The cumulative probability of continuous Engel class I seizure freedom since surgery at postoperative year 10 and afterward was 65.6%, with 92% of recurrences in years 1 to 3. Multivariable statistical analyses found that the selection for iEEG study was the most reliable predictor of seizure recurrence, with a mixed-effects model estimating that the Engel score in the iEEG cohort was higher by a mean (SD) of 1.1 (0.33) (P = .001). In patients with iEEG results, rapid seizure spread in less than 10 seconds was associated with recurrence (hazard ratio, 5.99; 95% CI, 1.7-21.1; P < .01). In the first 10 seconds of seizures, fast β power activity outside the resective margins in the lateral temporal cortex was significantly greater in patients whose seizures recurred compared with patients who were seizure-free (mean [SEM], 137.5% [16.8%] vs 93.4% [4.6%]; P < .05). CONCLUSIONS AND SIGNIFICANCE Rapid seizure spread outside anteromedial temporal resection resective margins plays a significant role in the surgical failure of drug-resistant TLE. Seizure control after epilepsy surgery might be improved by investigating areas of early spread as candidates for resection or neuromodulation.

Surgical outcomes and prognostic factors of drug‐resistant epilepsy secondary to encephalomalacia

“…An explanation for our result is that epileptogenic networks of early spread between the two hemispheres may have been present in patients with bilateral ictal onset rhythms. Without resecting sites of early seizure spread, favorable seizure outcomes were less likely to be achieved …”

“…Without resecting sites of early seizure spread, favorable seizure outcomes were less likely to be achieved. 38 Complete resection of epileptogenic zones has been identified as one of the most important predictors of postoperative seizure outcomes in patients with extratemporal lobe epilepsy. 23,39,40 However, we found no association between the completeness of resection and seizure outcomes.…”

Responsive neurostimulation for regional neocortical epilepsy

“…For patients in the latter category, large neocortical resections are associated with higher rates of seizure freedom but involve significant risk of postoperative neurologic deficits. Patients with broad epileptogenic networks are also more likely to have seizure recurrence after surgery, underscoring the need for alternative treatment options.…”

Early seizure spread and epilepsy surgery: A systematic review

“…10 Recent work suggests that the early seconds of a seizure may be a sensitive marker of the areas which, if not included in resections, lead to postoperative seizure recurrence. 11 A simple marker, such as timing of the first 10 seconds of a seizure and mapping out the cortex involved to incorporate into resection, could provide powerful decision-making capability. This review is aimed at summarizing the literature that is constructed in such a manner as to support or refute such a hypothesis.…”