From Pages to Practice

By Andrea Merrill, M.D.

Published October 25, 2017


About one third of patients with epilepsy have “drug-refractory epilepsy,” defined as failure of two appropriately selected and well-tolerated anti-epileptic drug therapies. Drug-refractory epilepsy in children can have significant consequences, including long-term effects on intellectual growth, psychosocial development, and quality of life. When medications fail to control seizures in children, an increasingly used option is targeted surgery to remove the area of the brain that is generating the seizure activity. However, high-quality randomized-controlled trials comparing surgery to medical therapy are lacking, particularly in children.

In this week’s issue of NEJM, Dwivedi et al. published the first randomized- controlled trial of surgery versus medical therapy in children with drug-refractory epilepsy. The trial was conducted at a single epilepsy referral center in India and involved 116 children and adolescents (age <18 years); 57 were assigned to surgery and 59 were assigned to a one-year waiting list for surgery (reflecting the usual waiting time for surgery) and remained on anti-epileptic therapy in the meantime. EEG and epilepsy protocol MRI were used to determine the extent and area of surgery, and a variety of surgeries were performed, including approximately 25% temporal lobectomy. The primary outcome was freedom from seizures at 12 months. Secondary outcomes included seizure occurrence during 12 months, seizure-severity, and various scores measuring IQ, social maturity, behavior, and quality of life.

After 12 months, 77% of patients in the surgery group and only 7% of patients in the waiting-list group had complete freedom from seizures (P<0.001). All patients who underwent temporal lobectomy and hypothalamic hamartoma surgeries were seizure-free. Seizure severity was also significantly improved in the surgery group compared to the waiting-list group. Although the waiting-list group had a significant reduction from baseline in IQ at 12 months, the difference between the two groups was not statistically significant. Both behavior and quality-of-life scores improved significantly in the surgical group. Serious adverse events occurred in about one third of patients in the surgery group, including hemiparesis in about one fourth of patients. Many patients with hemiparesis recovered some prior motor function.       

This is the first RCT to compare surgery versus medical therapy for drug-refractory epilepsy in children. Surgery was associated with significant improvement in almost all outcomes. Most impressively, 70 percentage points more patients in the surgery group than in the medical-therapy group were free from seizures at 12 months. Although this benefit came at the cost of an increase in surgery related adverse events, quality of life was improved in the surgery group. Deputy Editor, Dr. Allan Ropper notes, “Epilepsy surgery is widely employed in children, but it is valuable to have some metrics by which to judge its effect and to establish that behavior and social functioning are improved, at least at one year.”

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Andrea is a 2015-2016 NEJM Group Editorial Fellow. She is currently in the middle of her General Surgery residency at Massachusetts General Hospital and is also conducting research focusing on improvements in breast cancer surgery. She plans to pursue a fellowship in Surgical Oncology at the completion of her residency.