Neurosurgeon William Anderson and his team at the Johns Hopkins Neuromodulation and Advanced Treatments Center are exploring new ways to use neurostimulation to treat patients with epilepsy. 

The team is investigating new targets for a closed-loop responsive neurostimulation (RNS) system, a standard of care for patients with drug-resistant focal epilepsy. Looking to expand the treatment capabilities of RNS, Anderson and his team have been placing small depth electrodes in the anterior nucleus of the thalamus for patients whose seizures originate in both temporal lobes. This serves as an alternative to a tissue resection — a common surgery for patients with seizures originating in one temporal lobe — which is not effective with bitemporal involvement. 

For patients who have broader networks of seizure activity, particularly in the parietal region and posterior occipital region, neurosurgeons are studying the effectiveness of implanting electrodes in parts of the thalamus connected to those regions as well. 

Studies show that these methods are promising, and Anderson says there could be pediatric indications. While RNS doesn’t eliminate seizures, Anderson says previous research studies have shown a 40% to 60% reduction. 

“That can be meaningful for some patients, depending on how bad the seizures are, and it can also be meaningful for their caregivers, because a lot of these patients are quite disabled,” he says. “So if you can reduce the number of these events, then it just makes life easier for everyone involved.” 

Johns Hopkins is a leader in RNS, and participated in all multisite clinical trials related to the device the team uses, including the first trial that led to FDA approval of RNS. 

The team is also in early stages of research involving an implanted closed-loop stimulation device they call ePACStim (PAC stands for phase amplitude coupling), invented at Johns Hopkins, which aims to time stimulation pulses to specific phases in brain rhythmic activity. 

Additionally, Anderson and his team treat other forms of epilepsy with other standard-of-care neurostimulation methods. For patients who have had multiple surgeries or have seizures that originate in the limbic system, a deep brain stimulation (DBS) device can be implanted. These involve less internal hardware and, therefore, are easier to maintain over time. DBS can target areas similar to those that RNS targets in the thalamus, but rather than being a closed-loop system, it is always on, delivering stimulation pulses. 

For patients with drug-resistant partial onset seizures who did not have success with four or five medications and may have tried other neuromodulation treatments, vagus nerve stimulation (VNS) is also offered. This treatment, offered to pediatric patients and some adults — many of whom have disabilities because of their seizures — typically reduces seizures by 40% to 50%, according to published clinical trials. 

For Anderson, a major goal of continuing to research these treatments is to figure out which are most effective for different kinds of patients, and what treatment pathway they should follow if multiple neurostimulations methods are to be used. 

Gene Therapy Research 

Neurologist Joon Kang is principal investigator on a multisite study that is investigating AMT-6260, a gene therapy candidate that uses microRNA to knock down kainite-type glutamate receptors, which are implicated in the pathophysiology of mesial temporal lobe epilepsy (MTLE). This could be a potential alternative to traditional MTLE treatment, which typically involves removing tissue in surgery. 

Early data from the phase 1/2a clinical trial, presented at the 2025 International Epilepsy Conference in Lisbon, Portugal, showed that the treatment was well-tolerated with no major safety concerns, and had early and substantial seizure reduction post-treatment. 

“Over my career, I’ve seen our field move toward increasingly less invasive and more targeted treatments,” Kang says. “What’s exciting now is the chance to intervene at the level of epileptogenesis itself.” 

To refer an adult patient to the Johns Hopkins Epilepsy Center, call 410-955-9441. For pediatric patients, call 410-955-9100.