Advances in Responsive Neurostimulation in Pediatric Epilepsy at UPMC Children’s

Introduced nearly a decade ago and approved by the U.S. Food and Drug Administration (FDA) to treat specific forms of focal drug-resistant epilepsy (DRE) in adults (and other indications on an investigational basis), responsive neurostimulation (RNS) has recently begun to make its way into the realm of pediatric epilepsy treatment on an experimental or investigational basis. 

The Epilepsy Center in the Brain Care Institute at UPMC Children’s Hospital of Pittsburgh has been at the forefront of this evolving treatment paradigm in children with focal epilepsies that are not amenable to surgical resection or ablation, as well as children with primary generalized epilepsies that have failed to respond to other treatment modalities.

Leading the clinical and investigational uses of RNS in pediatric patients at UPMC Children’s are William Welch, MD, a neurologist and epileptologist in the Epilepsy Center who specializes in RNS, and Taylor Abel, MD, who is the surgical director of the Pediatric Epilepsy Surgery Program at UPMC Children’s.

“A large proportion of patients with primary generalized epilepsy have poor responses to, or fail medication therapies, while surgical options are very limited. The same is the case for individuals with focal epilepsy whose seizure origin(s) are located in highly eloquent areas of the brain, such as the motor and language cortices, that would be difficult or impossible to resect without causing major deficits in function or cognition,” says Dr. Welch. “RNS is beginning to open new treatment possibilities for these patients.”

To date, UPMC Children’s has conducted eight RNS implantation cases in pediatric patients as young as 9 years of age (more are currently scheduled), with two of the first pediatric cases using an implantation approach in the centromedian nucleus of the thalamus for individuals with primary generalized epilepsies. There have only been a handful of these procedures performed worldwide, and UPMC Children’s is leading the way in the clinical and investigational aspects of RNS to treat generalized forms of epilepsy.

How RNS Works

The RNS system currently approved by the FDA and employed by UPMC Children’s (the NeuroPace RNS® ) consists of a neurostimulator device implanted under the scalp and within the skull and is connected to two electrodes. These electrodes can be placed in various locations, either on the surface of the brain or within deep structures. The RNS system continuously monitors an individual’s brain activity, and over time “learns” what a patient’s epileptiform discharges look like. When the beginning of a seizure is detected by the device based on recognition of the epileptiform discharge pattern, it conducts a small electrical current to the electrodes to disrupt propagation or prevent a seizure from occurring. 

For the first month after implantation, the device records a patient’s seizure activity so that it can be programmed to recognize an individual patient's seizure patterns. After the initial "learning" period, the responsive stimulation is then switched on. It can be tuned or adjusted over time.

“Every patient is different. Some may experience immediate reductions in their seizure activity, and others may take some time for effects to gradually build over a period of months or years. It is generally the case that efficacy will increase over time, although how quickly or to what degree the device will be able to control a patient’s seizures does take time to develop,” says Dr. Welch.

Details From the First RNS Implantation at UPMC Children’s

The first RNS implantation completed at UPMC Children’s was performed on a 16-year-old young man with drug-resistant generalized primary epilepsy in May 2020. This individual was not a candidate for surgical resection due to the generalized nature of his epilepsy, and he experienced poor control of his seizures through multiple drug therapies, with many absence seizures each day.

"Our first RNS implantation patient was only the fifth pediatric patient in the world to have RNS implantation using an approach that places the device into the centromedian nucleus of the thalamus,” says Dr. Abel. “With its connections to the broader cerebral cortex and brain functions, the centromedian nucleus of the thalamus is of great interest as an area to target with neuromodulation techniques for patients with generalized epilepsies.”

In this particular case, the patient experienced a marked reduction in seizure activity almost immediately upon the device being switched on after the initial learning period.

"Our patient's seizure burden was reduced drastically in a very short time," says Dr. Welch. "His overall course since implantation has been good, and we all are pleased with his progress to date."

Clinical Trial Development

Drs. Welch, Abel, and colleagues are in the planning phase for a safety and feasibility trial of centromedian nucleus RNS implantation for primary generalized epilepsy in pediatric patients. This would be the first trial of its kind to rigorously test RNS use in pediatric epilepsy patients and report on safety and feasibility outcomes.

At present, the UPMC Children's team is confident that RNS could be implanted in children as young as six years of age; however, in its initial series of patients, the youngest individual has been 9 years old. With younger children, growth factors must be taken into consideration such that the device implantation does not interfere with or compromise skull growth and development.

“The big question that we have right now revolves around safety for RNS in pediatric patients, and in particular with younger children who have thinner skulls. The literature published so far points to RNS being a safe option, but we need more and better data. Our center is well-positioned and powered through our robust case volume and technological and surgical capabilities to launch such a trial," says Dr. Abel.