title: Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00040326.
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. engel@ucla.edu
authors.forename: Jerome
authors.initials: J
authors.lastname: Engel
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDermott
authors.forename: Samuel
authors.initials: S
authors.lastname: Wiebe
authors.forename: John T
authors.initials: JT
authors.lastname: Langfitt
authors.forename: John M
authors.initials: JM
authors.lastname: Stern
authors.forename: Sandra
authors.initials: S
authors.lastname: Dewar
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sperling
authors.forename: Irenita
authors.initials: I
authors.lastname: Gardiner
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Erba
authors.forename: Itzhak
authors.initials: I
authors.lastname: Fried
authors.forename: Margaret
authors.initials: M
authors.lastname: Jacobs
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Scott
authors.initials: S
authors.lastname: Mintzer
authors.forename: Karl
authors.initials: K
authors.lastname: Kieburtz
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology; D003071:Cognition; D004351:Drug Resistance; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012640:Seizures / Q000188:drug therapy / Q000601:surgery; D012919:Social Behavior; D013702:Temporal Lobe / Q000601:surgery*; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants