PITTSBURGH — A ketogenic diet seems to work synergistically with a vagus nerve stimulator to reduce refractory seizures by 50%–100% in children who use the methods concurrently, results of a small observational study found.
The concurrent use of the two therapies seems to represent a nonpharmacologic “rational polypharmacy,” Dr. Eric H.W. Kossoff reported in a poster at the annual meeting of the Child Neurology Society.
“Both therapies have multiple mechanisms of action and low side effects, and work well for all kinds of epilepsy, which is what an ideal polytherapy combination would entail,” Dr. Kossoff, a pediatric neurologist at Johns Hopkins Hospital, Baltimore, said in an interview. He had no explanation for the method of action behind apparent synergistic effects of the combined approach, however.
The combined approach also yields rapid results, he said. Of the 30 children studied, 10 had more than a 90% reduction in seizures within the first month of polytherapy.
Dr. Kossoff presented efficacy results in children (median age 10 years) from six epilepsy centers. All 30 of the children had intractable seizures (average 25 per week), and had been on an average of six medications before beginning the combined therapy.
About half of the study patients began with the ketogenic diet and added the vagus nerve stimulator (VNS) later. The other half began with the implant and then added the ketogenic diet.
After 3 months, 29 children were still using the concurrent therapy. Two had become seizure free, 8 had a 90%–99% reduction in seizure frequency, 11 had a reduction of 50%–90%, and 8 had a reduction of less than 50%.
By 6 months, 25 children were still using both methods. At that time, 2 were still seizure free; 5 children had a reduction of 90%–99%, 12 had a reduction of 50%–90%, and 6 had a reduction of less than 50%.
At 1 year, 15 children were still undergoing both therapies, but none were seizure free; five children had a reduction of 90%–99%, seven a reduction of 50%–90%, and three a reduction of less than 50%.
Most of the children who stopped the combination therapy before 1 year dropped the ketogenic diet.
When Dr. Kossoff examined predictive factors, only age and length of VNS off-time were significant. Children who had more than a 90% seizure reduction were significantly younger than were those who had less than a 90% reduction (8.6 years vs. 12 years). Those who had a 5-minute VNS off-time also had significantly better results than did those with shorter off-times.
“Even though both the ketogenic diet and the VNS are effective therapies with low rates of side effects, only about 2% of pediatric epilepsy patients are on both concurrently,” Dr. Kossoff said. “Our recommendation would be to try one or the other first, and if efficacy is good (50% or better) but not superb, consider adding the second,” he said.