Five patients with drug-resistant idiopathic generalized epilepsy responded well to responsive neurostimulation (RNS) of the centromedian nucleus of the thalamus, according to an abstract presented at the 2022 American Epilepsy Society in December.
The RNS procedure involves implanting a device in the brain, which records abnormal electrical activity and then emits an electrical pulse when it recognizes that pattern again, similar to a pacemaker. The US Food and Drug Administration approved it for use in focal epilepsy in 2013.
RNS is not approved for idiopathic generalized epilepsy (IGE), which accounts for about one-third of all epilepsies. About 20 to 30 percent of patients with IGE do not respond to drug treatments and continue to have seizures, said Andrew Zillgitt, DO, a study author and the director of the adult epilepsy program at Beaumont Health in Royal Oak, MI.
In the study, five patients with drug-resistant IGE underwent RNS implantation, and quality of life was assessed at clinic visits with a subjective questionnaire. The average age at RNS implantation was 36.6 years old (ranging in age from 25 to 51), with the average follow-up after surgery at 18 months.
All patients reported “at least a 75 percent reduction in the frequency of disabling seizures," and two patients reported remaining free of generalized tonic-clonic seizures, Dr. Zillgitt said.
Similar small studies are underway nationwide using RNS on IEG, Dr. Zillgitt said. Beaumont has added a sixth patient to its RNS study, following one patient for three years. Typically, the battery in the implant lasts for about eight years, he said.
“Other places had already started doing this, and their returns looked very promising," Dr. Zillgitt said, adding that he had a lot of respect for the patients who were brave enough to try a new procedure.
Michael R. Sperling, MD, FAAN, chief of the division of epilepsy and director of the Jefferson Comprehensive Epilepsy Center at Thomas Jefferson University in Philadelphia, said that although it's interesting that electrodes in some people might improve their seizures, “you can't draw any conclusion from this other than there is a suggestion of the possibility of a benefit and a proper controlled study should be done."
He noted that the study was challenging because it was small, did not have a control group, and did not account for the placebo surgical impact, which has been well documented.
“When you drill holes in someone's head and stick probes in the brain, you commonly get positive effects, especially in small numbers of people," said Dr. Sperling, who said he frequently sees similar studies as editor-in-chief of Epilepsia. “There's a clear effect to just touching the brain, independent of stimulation."
Dr. Zillgitt agreed that the placebo effect may happen, but that prolonged benefits beyond two to three months are less likely.
"We could expect some improvement following implantation of the device, but it is unlikely thhat it would be sustained for 18 months, which was the average follow up in this study," he said, adding that in the pivotal clinical trial for RNS, therapy wasn't initiated for two months after implantation in an attempt to avoid a confounding implantation effect.
Dr. Sperling added that it's hard to know if patients accurately report their seizure activity because sometimes they are unaware that they have them. And patients often present a happier scenario than exists because they want to please their doctors, and vice versa, he said.
Barbara C. Jobst, MD, PhD, FAAN, professor and chair of neurology at the Geisel School of Medicine at Dartmouth University, said patients with implants typically experience a decrease in seizures for about five months, but then it returns to their baseline numbers. It's important to look at the long-term impacts of these devices, she said.
A larger multicenter, single-blind, randomized, controlled study underway called NAUTILUS aims to enroll a maximum of 100 patients over 18 to address tonic-clonic seizures in the setting of IGE. The expected completion date is December 2026.
Jefferson is part of that study, Dr. Sperling said. Dr. Zillgit noted that Corewell Health Butterworth Hospital in the Beaumont health system is also part of that trial. But if patients don't qualify for the NAUTILUS trial, Dr. Zillgitt's group plans to keep its research moving forward and hopes to study different settings of the implant, particularly looking at memory test speed and quality-of-life scores after RNS transplantation.
