Related Experiment Video
Updated: May 24, 2026
Anteromesial Temporal Lobectomy for Medically Intractable Temporal Lobe Epilepsy: An Operative Study
Published on: August 15, 2025
Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial
Jerome Engel1, Michael P McDermott, Samuel Wiebe
1Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. engel@ucla.edu
Context:
Despite reported success, surgery for pharmacoresistant seizures is often seen as a last resort. Patients are typically referred for surgery after 20 years of seizures, often too late to avoid significant disability and premature death.
Objective:
We sought to determine whether surgery soon after failure of 2 antiepileptic drug (AED) trials is superior to continued medical management in controlling seizures and improving quality of life (QOL).
Design, Setting, And Participants:
The Early Randomized Surgical Epilepsy Trial (ERSET) is a multicenter, controlled, parallel-group clinical trial performed at 16 US epilepsy surgery centers. The 38 participants (18 men and 20 women; aged ≥12 years) had mesial temporal lobe epilepsy (MTLE) and disabling seizues for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs. Eligibility for anteromesial temporal resection (AMTR) was based on a standardized presurgical evaluation protocol. Participants were randomized to continued AED treatment or AMTR 2003-2007, and observed for 2 years. Planned enrollment was 200, but the trial was halted prematurely due to slow accrual.
Intervention:
Receipt of continued AED treatment (n = 23) or a standardized AMTR plus AED treatment (n = 15). In the medical group, 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery.
Main Outcome Measures:
The primary outcome variable was freedom from disabling seizures during year 2 of follow-up. Secondary outcome variables were health-related QOL (measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 [QOLIE-89] overall T-score), cognitive function, and social adaptation.
Results:
Zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure free during year 2 of follow-up (odds ratio = ∞; 95% CI, 11.8 to ∞; P < .001). In an intention-to-treat analysis, the mean improvement in QOLIE-89 overall T-score was higher in the surgical group than in the medical group but this difference was not statistically significant (12.6 vs 4.0 points; treatment effect = 8.5; 95% CI, -1.0 to 18.1; P = .08). When data obtained after surgery from participants in the medical group were excluded, the effect of surgery on QOL was significant (12.8 vs 2.8 points; treatment effect = 9.9; 95% CI, 2.2 to 17.7; P = .01). Memory decline (assessed using the Rey Auditory Verbal Learning Test) occurred in 4 participants (36%) after surgery, consistent with rates seen in the literature; but the sample was too small to permit definitive conclusions about treatment group differences in cognitive outcomes. Adverse events included a transient neurologic deficit attributed to a magnetic resonance imaging-identified postoperative stroke in a participant who had surgery and 3 cases of status epilepticus in the medical group.
Conclusions:
Among patients with newly intractable disabling MTLE, resective surgery plus AED treatment resulted in a lower probability of seizures during year 2 of follow-up than continued AED treatment alone. Given the premature termination of the trial, the results should be interpreted with appropriate caution.
Trial Registration:
clinicaltrials.gov Identifier: NCT00040326.
Insights
Early epilepsy surgery for drug-resistant mesial temporal lobe epilepsy (MTLE) significantly reduced disabling seizures compared to continued antiepileptic drug (AED) treatment. This suggests earlier surgical intervention can improve outcomes for patients with intractable epilepsy.
Area of Science:
- Neurology
- Neurosurgery
- Clinical Trials
Background:
- Pharmacoresistant epilepsy surgery is often delayed, leading to significant disability and premature death.
- Patients typically undergo surgery after 20 years of seizures, potentially missing the optimal treatment window.
Purpose of the Study:
- To compare the efficacy of early epilepsy surgery versus continued medical management in controlling seizures.
- To assess the impact of early surgery on patients' quality of life (QOL).
Main Methods:
- The Early Randomized Surgical Epilepsy Trial (ERSET) was a multicenter trial involving 38 participants with newly intractable MTLE.
- Participants were randomized to either continued antiepileptic drug (AED) treatment or anteromesial temporal resection (AMTR) plus AEDs.
- Outcomes included seizure freedom at 2 years and changes in QOL, cognitive function, and social adaptation.
Main Results:
- 11 of 15 surgical patients achieved seizure freedom in year 2, versus 0 of 23 in the medical group (P < .001).
- Surgical intervention showed a statistically significant improvement in Quality of Life in Epilepsy 89 (QOLIE-89) scores when post-surgery data from the medical group were excluded (P = .01).
- Memory decline occurred in 36% of surgical patients, consistent with existing literature.
Conclusions:
- Resective surgery combined with AED treatment significantly reduces seizure probability in patients with newly intractable MTLE compared to AEDs alone.
- Early surgical intervention appears to be a more effective strategy for seizure control in this patient population.
- The trial was halted prematurely, necessitating cautious interpretation of the findings.
