Surgery or Medical Management for Refractory Pediatric Epilepsy?

Children and adolescents with drug-resistant epilepsy who undergo surgery appear to have significantly higher rates of seizure freedom and better quality of life and behavior scores at 12 months than those who receive medical therapy alone, according to a study published in the October 26, 2017, issue of the New England Journal of Medicine. Serious anticipated adverse events may occur after surgery, however.

“The improvements that were observed in other cognitive, behavioral, and quality of life scores in the surgery group may have been due to a reduction in the frequency of seizures; conversely, the deterioration in these measures in the medical-therapy group may be attributed to a continuation of seizures,” said Rekha Dwivedi, PhD, a postdoctoral fellow at the All India Institute of Medical Sciences in New Delhi, and colleagues.

Rekha Dwivedi, PhD

Comparing Methods Intended to Improve Outcomes

Children and adolescents with drug-resistant epilepsy have an increased risk of poor long-term intellectual and psychosocial outcomes, along with a poor health-related quality of life. Neurosurgical treatment may improve seizures in children and adolescents with drug-resistant epilepsy, but evidence of benefit from randomized trials in this age group is limited.

A meta-analysis of uncontrolled studies comparing seizure outcomes of surgeries in children indicated that 74% of patients with brain lesions and 45% without lesions had become seizure-free at one year of follow-up. In a retrospective analysis involving 142 children and adolescents with drug-resistant epilepsy who had undergone surgery, 79.3% of patients were free from disabling seizures after a mean follow-up of approximately four years.

To investigate the effects of surgery further, Dr. Dwivedi and colleagues performed a single-center trial. They sought to compare epilepsy surgery with continued medical therapy alone in patients on a waiting list for surgery.

Researchers randomized 116 patients age 18 or younger with drug-resistant epilepsy to brain surgery appropriate to the underlying cause of epilepsy, along with appropriate medical therapy, or to medical therapy alone. Patients for whom there was no consensus regarding the location of an epileptic focus, patients who had any other systemic illness, and patients with a history of status epilepticus were excluded.

Participants assigned to the surgery group underwent the procedure within a month after randomization. Those assigned to the medical-therapy group remained on a waiting list. Surgery for these patients was scheduled for one year or longer after randomization. The primary outcome was seizure freedom at 12 months. Secondary outcomes included the Hague Seizure Severity scale score, the Binet–Kamat intelligence quotient or the social quotient on the Vineland Social Maturity Scale, the T score on the Child Behavior Checklist, and the Pediatric Quality of Life Inventory score.

Most of the Surgery Group Became Seizure-Free at 12 Months

Median age was 9 in the surgery group and 10 in the medical-therapy group. In all, 14 patients had temporal lobe resections, 12 patients had resection of a lesion in a lobe other than the temporal lobe, 15 patients had hemispherotomy, 10 patients had a corpus callosotomy, and six patients had a disconnection or resection of hypothalamic hamartoma.

At 12 months, 44 of 57 patients (77%) in the surgery group became seizure-free, compared with four of 59 patients (7%) in the medical-therapy group. Furthermore, 21 patients (37%) in the surgery group were completely seizure-free during the entire 12-month period.

All patients who had undergone temporal lobectomy or hypothalamic hamartoma surgeries were seizure-free at the last follow-up. Of the patients who had undergone extratemporal resection or hemispherotomy, 11 of 12 patients (92%) and 13 of 15 (87%), had complete freedom from seizures, respectively.

Two of 15 patients (13%) in the medical-therapy group who were on the waiting list for a temporal lobectomy were seizure-free at 12 months, along with one of 19 patients (5%) who were on a waiting list for extratemporal resection and one of 16 patients (6%) who were waiting for a corpus callostomy. Patients with a planned hemispherotomy or intervention for hypothalamic hamartoma were not seizure-free at 12 months.

In addition, between-group differences in the change from baseline to 12 months significantly favored surgery with respect to the Hague Seizure Severity scale score, the Child Behavior Checklist, the Pediatric Quality of Life Inventory, and the Vineland Social Maturity Scale, but not the Binet–Kamat intelligence quotient, said the researchers.

Adverse Events and Study Limitations

Serious adverse events occurred in 19 patients (33%) in the surgery group and no patients in the medical-therapy group. Monoparesis occurred in two patients who had undergone temporal lobectomy or resection of parietal focal cortical dysplasia. Hemiparesis occurred in 15 patients who had undergone hemispherotomy. Finally, generalized hypotonia and language deficits occurred in one patient who had undergone frontal lobectomy.