Treatment of Refractory Mesial Temporal Lobe Epilepsy

Abstract

To the Editor: Dr Engel and colleagues presented important additional evidence on the superiority of surgical therapy over antiepileptic drugs (AEDs) in the treatment of refractory mesial temporal lobe epilepsy (MTLE). Their results corroborate and expand the findings of a previous randomized controlled trial, which led the American Academy of Neurology to issue a practice parameter in 2003 recommending surgery as the treatment of choice for pharmacoresistant MTLE. While the greater efficacy of surgical treatment for seizure control in MTLE is well established, the question of timing of surgery is still controversial. Clinicians generally perceive surgery as a last resort due to concern regarding the risks of adverse effects following surgical intervention and either fail to refer patients or refer them too late. Although not a universal finding, memory impairment has often been reported after an anterior temporal lobe resection and may compromise the patient’s well-being and social functioning, even when seizure-free. However, MTLE is now regarded as a progressive disease and therefore it is critical to assess the comparative effect on health-related quality of life (HRQOL) and the psychosocial status of patients undergoing each treatment approach to make an informed decision concerning the use of surgery or pharmacotherapy. With the premature termination of the trial after only 38 patients were enrolled, the comparative effect of early surgery on cognition and HRQOL remains unanswered. The declared primary outcome of the Early Randomized Surgical Epilepsy Trial (ERSET) was seizure freedom, but the large planned sample size (200 patients) is not justifiable based on the expected difference in the primary outcome because there was previous evidence indicating that the surgical approach is superior in cases of refractory MTLE. In fact, supplementary material previously published describing the study design for ERSET confirms that “sample size was instead chosen largely to address the important secondary aim of examining treatment group differences in mean change in HRQOL.” Moreover, in 1999, when the original plan for ERSET was published, it stated that, at the end of 2 years, the primary outcome measure would be a quantitative assessment of HRQOL; seizure recurrence was defined as a secondary outcome. Early surgery can benefit patients with MTLE. Future trials with larger samples and longer follow-up should address the issue of whether surgery can also improve HRQOL compared with the natural history of the disease in appropriately selected patients with MTLE, in addition to providing better seizure control compared with medication.