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Original Investigation
December 3, 2018

Association of Seizure Spread With Surgical Failure in Epilepsy

Author Affiliations
  • 1Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut
  • 2Department of Neurology, Yale University School of Medicine, New Haven, Connecticut
  • 3Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut
JAMA Neurol. 2019;76(4):462-469. doi:10.1001/jamaneurol.2018.4316
Key Points

Question  Why do many patients continue to experience seizures after undergoing surgery for temporal lobe epilepsy?

Findings  In this cohort study of 118 patients, rapid seizure spread to regions outside resective medial temporal lobe margins was associated with seizure recurrence after surgery in patients who underwent identical medial temporal resections for drug-resistant temporal lobe epilepsy.

Meaning  In patients with drug-resistant epilepsy, areas of early seizure spread may represent an epileptogenic network and should be investigated as targets for resection or neuromodulation.


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.