To date, thalamic responsive neurostimulation (RNS) has shown real potential in the treatment of patients with drug-resistant epilepsy. Mark Richardson (Massachusetts General Hospital, Boston, USA) outlines why it has proven to be such a promising therapy and what the future may hold for this modality—including large-scale trials, alternative brain disorders, and more.
Could you briefly outline thalamic RNS and how it differs from other brain stimulation techniques?
There are two types of implantable brain stimulators—those that do not record brain activity, like standard deep brain stimulation (DBS), and those that do, like the RNS system (NeuroPace). DBS of the thalamus is approved to treat focal epilepsy, and RNS is also approved for focal epilepsy, but RNS of the thalamus is relatively new because the field has recently come to understand that seizures can be detected in the thalamus and that responsive stimulation there can affect wide cortical networks. This is impactful for patients because RNS is tailored to their specific brain activity and their physicians can also use the recorded brain data to evaluate how well a medication is working; side-effects from medication are a huge problem for many people with epilepsy.
How long has this technique been used for epilepsy and to what extent?
RNS has been US Food and Drug Administration (FDA)-approved for focal epilepsy since 2014, and we continue to evolve that use, including as a long-term diagnostic tool and in combination with other minimally invasive surgical therapies like laser ablation. Epilepsy surgery, however, including neuromodulation, is vastly underutilised. Only 5% of people with drug-resistant epilepsy who would benefit from surgery receive therapy. This represents a public health crisis. Epilepsy is the third most-common serious brain disease after stroke and Alzheimer’s—for what other disease would we accept such a treatment gap? Brain stimulation therapies can reduce seizures by 70%, on average, and contribute to other improvements in quality of life, and the medical field as a whole needs to act more urgently to reduce bias towards people with epilepsy and towards surgery.
Why is thalamic RNS particularly suited to this indication?
Thalamic RNS is particularly well suited to regional, multifocal and generalised epilepsies because of its ability to affect broad cortical regions via thalamocortical connections that are activated by thalamic stimulation. This strategy allows us to overcome limitations of focal surgeries that cannot adequately address seizures that originate from wide networks in the brain. At the same time, the information recorded on the device provides objective information about the effects of stimulation on these seizure networks, allowing us to personalise the detection and stimulation settings to the individual person’s brain activity.
Have there been any recent breakthroughs that build on existing evidence for this therapy?
One recent breakthrough is the emerging use of thalamic RNS for idiopathic generalised epilepsy (IGE). This group of epilepsies are unique in that the thalamus seems to participate in the origination of seizures, which in other types of epilepsies originate exclusively in the cortex. For this reason, IGE may be uniquely well suited for a therapy that both detects and stimulates in the thalamus. We implanted the first thalamic RNS system in a young lady with IGE in 2017—it worked really well, and we have continued to use this therapy for people with IGE whose seizures do not respond adequately to medication. We recently published the first case series of these patients, other groups are publishing their experiences too, and the use of thalamic RNS for IGE appears to be taking off.
Do you think more research is required and, if so, what direction should these efforts take?
Based on wide interest from the epilepsy field, a nationwide clinical trial sponsored by the company who manufactures the RNS system, NeuroPace, was launched very recently to seek FDA approval for using thalamic RNS to treat IGE in adults and children as young as 12 years old. If the trial is successful, it will open this therapy to more than 300,000 people in the USA who are suffering from drug-resistant primary generalised epilepsy.
More broadly, what would you say the future holds in this space?
A main advantage to RNS is the ability to use a person’s own brain data to inform therapy and to measure the therapy’s effects directly. Beyond this evolution of personalised medicine, there are huge potential upsides for patients to interact with their own data. Review of the brain recordings, which are accessed through a cloud-based platform, together with their epilepsy doctor is a wonderful way to strengthen the patient-physician relationship. In the future, applications of the technology will evolve to use brain recordings to give patients predictions about which times of the day, week, or month, their seizures are most likely to occur. Imagine how helpful this would be if you constantly spent your time worrying about when your next seizure was going to occur, and whether it would happen in a setting that could lead to anything from social embarrassment to death.
Could thalamic RNS hold major benefits in other conditions too?
RNS of the thalamus, and other areas in the brain that are central hubs in specific behavioural circuits, holds promise for treating many brain disorders—including addiction, depression, post-traumatic stress disorder and Parkinson’s disease. There is massive interest within the translational neuroscience community in studying brain function across these different diseases to understand the best way to employ this technology. It is important to recognise that funding from the US Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has been fuelling a great deal of work in this field, and continuous support of the BRAIN Initiative by US Congress is critical for long-term success.
DISCLOSURES: Richardson indicated that he has received compensation from NeuroPace for consulting and educational presentations.