23 July 2022

Prepared by: Abrar Ahmed, BSc. (Hons), MD Candidate (2025) – Junior Blog Manager; aahmed2025@meds.uwo.ca and
Dr. Jasleen Saini, MD – Senior Blog Manager; jasleen.saini@usask.ca
Reviewed by: Dr. Amirti Vivekanandan

CaMSIGN Blog: A Randomized Controlled Trial of Surgery for Temporal-Lobe Epilepsy: A Summary for Medical Students

Surgery is a viable therapeutic option for patients with intractable temporal lobe epilepsy. However, it was not always the case. Until a landmark investigation conducted by the Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study Group, surgery was not widely considered for this condition.

At the time of the study’s publication in The New England Journal of Medicine, it was estimated that just 1.5% of patients eligible for temporal lobectomy patients in the United States underwent an operation for temporal lobe epilepsy each year. This eligibility is defined by whether the patients are considered to have surgically remediable epileptic syndrome. The researchers sought to find evidence supporting the therapeutic benefits of providing early surgery to patients with intractable temporal lobe epilepsy rather than waiting until the complex medication regimen failed. Therefore, the investigators conducted a four-year-long parallel-group randomized controlled trial that compared surgery to medical therapy in patients with temporal lobe epilepsy.

Eligible patients were at least 16 years old and affected by temporal lobe seizures for more than a year. The seizures had to have occurred once per month on average despite the use of at least two antiepileptic drugs. Participants were excluded from the trial if they had brain lesions requiring immediate surgery, active psychosis, IQ <70, progressive central nervous system disorders, pseudo seizures, previous operation for epilepsy, or focal extratemporal spikes as evident by EEG or MRI. This culminated in 80 patients being enrolled on the trial, with each being randomly assigned to either the antiepileptic medication group or the surgery group. The primary outcome that was evaluated was an absence of seizures that distorted awareness of self and surroundings. The investigators also examined the rate of seizure occurrence, severity, quality of life, disability, and death as secondary outcomes.

Of the 40 patients assigned to the surgical group, 36 patients were eligible and consented to surgery. Of the four that did not receive surgery, one did not consent, two were classified as non-eligible based on presurgical tests such as EEG and MRI, and one did not experience seizures during hospital investigations.

Four people who did receive surgery had adverse effects related to the procedure such as thalamic infarct or decline in verbal memory.  18% of patients in the surgical group developed depression. One patient developed transient psychosis, and 22 developed asymptomatic visual field deficits. Eight patients in the medical group developed depression, one developed transient psychosis, and one died 7.5 months into the study. 

58% of patients in the surgical group were free from seizures that impaired awareness at one year. Only 8% of patients in the medical group had the same outcome. The researchers concluded that the number to treat was two patients (95% confidence interval, 1.5-3) resulting in one additional patient becoming free of seizures that reduced awareness after one year.

Furthermore, the investigators concluded that three patients were required to undergo a surgical procedure (95% confidence interval, 2-5) to result in one additional patient becoming completely seizure free for a full year regardless of whether there was a reduction in awareness. The quality of life was better for patients in the surgical group than in the medically treated group. This was demonstrated through a greater employment rate and school attendance in the surgical group relative to the medical treatment group.

In conclusion, this trial demonstrated that surgery was a superior treatment options relative to medical therapy for quality of life and seizure control for patients with poorly controlled temporal lobe epilepsy. The morbidity that occurred because of the surgery was similar to what had been previously reported in the literature. However, the investigation failed to answer the question of when the optimal timing for surgery is. Despite this, the investigation was a landmark study as it presented a new treatment option for clinicians and patients to try in the face of poorly controlled temporal lobe epilepsy to prevent morbidity or mortality.

1. Wiebe, S., Blume, W. T., Girvin, J. P., & Eliasziw, M. (2001). A randomized, controlled trial of surgery for temporal-lobe epilepsy. New England Journal of Medicine345(5), 311-318.

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