Timing of Surgical Intervention for Epilepsy

Worldwide epilepsy accounts for 1% of the burden of disease, a proportion equal to that of lung cancer in men and breast cancer in women. Nearly 80% of the cost of managing and treating epilepsy is associated with the 20% to 40% of patients who have medically intractable disease, according to researchers.

The most common cause of drug-resistant seizures is temporal lobe epilepsy (TLE), which can be treated surgically. Surgery for TLE is the treatment of choice according to practice parameters from the American Academy of Neurology; however, surgery to treat TLE is “delayed and underutilized,” the researchers said.

They noted that the average duration of TLE for patients referred for surgery is 22 years, >10 years after failed treatment with antiepileptic drugs (AEDs). Even following publication of a randomized controlled trial demonstrating the efficacy of surgery for patients with long-standing TLE, there has not been a decrease in time to surgical referral.

To compare outcomes of surgery with continued pharmacotherapy, the National Institute of Neurological Disorders and Stroke recently funded ERSET (Early Randomized Surgical Epilepsy Trial). Trial results were reported in the Journal of the American Medical Association [2012;307(9):922-930].

ERSET was a multicenter, controlled, parallel-group clinical trial conducted at 16 epilepsy surgery centers in the United States. There were 38 participants (18 men and 20 women) ≥12 years of age. The researchers had intended to enroll 200 participants, but the trial was stopped prematurely due to slow accrual.

The primary outcome measure was freedom from disabling seizures during year 2 of follow-up. Secondary outcome measures included health-related quality of life (QOL), cognitive function, and social adaptation.

Inclusion criteria were mesial TLE (MTLE) and disabling seizures for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs, and being viable candidates for anteromesial temporal resection based on a standardized presurgical evaluation protocol.

Of the 38 patients identified as surgical candidates, 23 were randomized to the medical group and 15 to the surgical group. There were 2 adolescents in the study; both were in the medical group. Mean age in the medical group was 30.9 years, compared with 37.5 years in the surgical group. The medical group included 15 men (60.9%) compared with 4 (26.7%) in the surgical group. All other characteristics were comparable at baseline.

Of the patients in the medical group, 19 provided seizure logs and all had seizures recorded during year 2 of follow-up. In the surgical group, 14 patients provided seizure logs and 2 had seizures during year 2. In an intention-to-treat analysis, the mean improvement in Quality of Life in Epilepsy 89 overall T score was higher in the surgical group at month 24 compared with the medical group, but the difference did not reach statistical significance (12.6 vs 4.0 points; treatment effect, 8.5; 95% confidence interval, –1.0 to 18.1; P=.08).

When excluding data obtained after surgery from participants in the medical group (n=6), the effect of surgery on overall QOL was statistically significant at month 24 (P=.01). There were no significant differences between the treatment groups in primary memory and nonmemory measures, notwithstanding that those in the medical group did tend to perform better on memory measures, particularly at month 24 (P=.08).

Adverse events included a transient neurologic deficit attributed to a magnetic resonance imaging–defined postoperative stroke in 1 patient in the surgery group and 3 cases of status epilepticus in the medical group.

The researchers summarized the results, noting that “among patients with newly intractable disabling MTLE, resective surgery plus AED treatment results 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.”