By Jeremy Koff, senior consulting editor
September 22, 2026 | Over the past two decades, neuromodulation for drug-resistant epilepsy (DRE) has evolved from a single approved therapy—vagus nerve stimulation—into a broader field that includes responsive neurostimulation, deep brain stimulation, less-invasive cortical stimulation and emerging optical, thermal, and sensing-enabled systems. Antiseizure medications remain the first-line treatment, but approximately one-third of people with epilepsy continue to experience seizures despite pharmacologic therapy, creating a substantial unmet clinical need.
Three implantable neuromodulation therapies currently have FDA approval for epilepsy: LivaNova’s VNS Therapy, NeuroPace’s RNS system, and Medtronic’s anterior thalamic DBS therapy. Together, these platforms have demonstrated that electrical stimulation can provide meaningful seizure reduction for appropriately selected patients whose seizures remain uncontrolled and for whom resective or ablative surgery is unsuitable, unsuccessful, or not pursued. Each therapy occupies a distinct clinical niche based on seizure type, target anatomy, degree of invasiveness and stimulation strategy.
The field is now entering a second phase characterized by greater personalization, closed-loop sensing, less-invasive implantation, and technologies designed to reduce surgical burden while preserving clinical efficacy.
This overview focuses on therapeutic devices and excludes systems used solely for seizure monitoring or diagnostic evaluation.
FDA-Approved Implantable Platforms
LivaNova’s VNS Therapy is FDA-approved as an adjunctive therapy to reduce seizure frequency in patients aged four and older with refractory partial-onset seizures. Its use in generalized epilepsies should be distinguished from the narrower FDA-labeled indication. The system, originally developed by Cyberonics, received FDA premarket approval in 1997. It uses a pulse generator implanted in the chest and a helical lead placed around the left cervical vagus nerve. It avoids intracranial leads and craniotomy. Conventional stimulation is intermittent and programmed. SenTiva’s AutoStim feature can add stimulation after detecting a rapid heart-rate increase that may accompany a seizure; this is physiology-triggered therapy, not direct EEG-based closed-loop stimulation. Continuous improvements—including AutoStim and smaller pulse generators—have helped sustain VNS’s long commercial history.
NeuroPace pioneered responsive neurostimulation, introducing a closed-loop approach that delivers stimulation when abnormal activity is detected. The RNS neurostimulator is seated in the skull and connected to one or two depth or cortical strip leads placed at identified seizure foci. It continuously senses electrocorticographic activity, detects patient-specific abnormal patterns and delivers brief electrical pulses. Selected recordings are stored over time, creating a longitudinal intracranial EEG dataset that can inform device programming, medication management, seizure lateralization and other clinical decisions. It first received FDA approval in November 2013. Beyond therapy, the RNS System provides chronic intracranial EEG data that can assist physicians in optimizing treatment.
Medtronic’s DBS therapy uses bilateral leads implanted in the anterior nucleus of the thalamus and connected to a chest pulse generator, modulating seizure propagation across distributed brain networks. The FDA approved its device for the treatment of epilepsy in 2018 as adjunctive therapy for adults with partial-onset seizures, with or without secondary generalization, refractory to three or more antiseizure medications. The labeling is based on patients who averaged at least six seizures per month during the three months before implantation, with no more than 30 days between seizures. Long-term follow-up from the SANTÉ trial has supported anterior thalamic DBS as an option for adults with focal drug-resistant epilepsy, particularly when seizures arise from or propagate through distributed networks. Rather than competing directly, VNS, RNS and DBS have become complementary options selected according to seizure localization, patient anatomy, surgical candidacy, and physician preference.
Meriem Bensalem-Owen, director of the University of Kentucky’s comprehensive epilepsy program, sees the ability to act directly on seizure networks as an important distinction between neurostimulation and pharmacologic treatment. “One of the unique advantages of neurostimulation is its ability to directly modulate the epilepsy network by delivering stimulation to a specific target, or ‘hub.’ These neuromodulatory effects may continue to evolve, with clinical improvement occurring even after prolonged periods without changes to stimulation parameters.”
Emerging Implantable Products
PRECISIS EASEE: focal stimulation without craniotomy
EASEE (Epicranial Application of Stimulation Electrodes for Epilepsy) places an approximately 1-mm-thick electrode array under the scalp over the individualized epileptic focus, connected to a chest generator. The electrode is outside the skull; the objective is to focus current through the skull using a Laplacian geometry and proprietary stimulation patterns. It is therefore best categorized as fully implantable, focal, open-loop epicranial electrical neuromodulation—not non-invasive stimulation.
The company’s 2025 presentation describes a CE-marked system requiring no craniotomy with personalized placement, patient-controlled access, and a combination of high-frequency alternating and DC-like stimulation. The company reports responder rates of 53% at six months and 65% at two years in a 26-patient study. These results should be interpreted cautiously given the small sample, evolving follow-up, attrition, and differences in study design that preclude direct comparison with trials of other devices.
In November 2025, PRECISIS announced FDA approval of its investigational device exemption application to initiate EASEE4US, a pivotal study expected to enroll approximately 200 patients. The system previously received Breakthrough Device designation.
Commercially, EASEE could occupy the middle of the invasiveness continuum: more focal than VNS and less invasive than RNS/DBS. Its form factor may appeal to patients seeking to avoid a craniotomy. The pivotal study is intended to determine whether epicranial stimulation can produce sufficiently consistent and durable outcomes, particularly when seizure networks are deep or incompletely localized.
Adraxe: minimally invasive subgaleal closed-loop system
Adraxe is developing a precision neuromodulation system for epilepsy. The proposed closed-loop platform is intended to detect seizure activity and respond with targeted electrical stimulation without placing electrodes or leads within the brain. Adraxe positions the technology as a potentially less invasive alternative to established device-based treatments, including responsive neurostimulation, deep-brain stimulation and vagus-nerve stimulation. The system remains in development and is undergoing clinical validation.
Adraxe’s initial evidence comes from its Budapest 1.0 pilot study. According to company materials, expert review of EEG recordings found shorter seizure durations among stimulated events than among control events, with statistical significance reported in an analysis limited to patients with at least four observations. The small study and selected analysis make the findings preliminary.
Synergia Medical NAO.VNS: optoelectronic power delivery to a proven target
Synergia Medical’s investigational NAO.VNS system uses an implanted pulse generator to transmit light through polymer optical fibers. Miniature photovoltaic cells near the electrode convert that light into electrical stimulation of the vagus nerve. The therapeutic output is therefore electrical VNS delivered through an optical power-transmission architecture, rather than photobiomodulation, in which light itself is intended to produce a biological effect.
In company materials, Synergia projects a 15-year battery life, approximately one minute of daily charging, MRI/fMRI advantages, low metal content, and resistance to electromagnetic interference. These remain company-reported design claims and engineering targets pending independent validation and eventual regulatory labeling. At the 2025 Neurotech Leaders Forum at imec in Belgium, Synergia reported that five patients had received implants in the AURORA first-in-human study and that the cohort had reached the three-month primary safety endpoint without serious adverse events or implant failures. The company also reported a 40% responder rate and one seizure-free patient at six months. Given the five-patient sample, these efficacy findings should be considered preliminary.
The AURORA first-in-human study is designed to enroll up to 10 adults at two sites with 24-month safety follow-up. The platform’s strategic differentiation is engineering rather than a new neural target: longer life, rechargeability, imaging access, and potentially higher-energy therapy.
iVEAcare: emerging sensing-enabled implant
iVEAcare emerged from stealth in 2024 with a $27.5 million Series A financing to develop neuromodulation therapies. The company was formed through a collaboration involving three organizations, including Alfred E. Mann-founded huMannity Medtec. Published patent filings describe a seizure-management system incorporating sensing, detection, and algorithm-based analysis. In June 2026, a first feasibility study was registered to assess the safety and performance of the iVEAcare Neuromodulation System in drug-resistant epilepsy. The study is expected to enroll 30 patients at two Australian centers, including patients with refractory focal-onset or generalized seizures. Public information about the system remains limited, although patent filings provide some insight into its proposed design and functionality.
Noninvasive Neuromodulation
Electrical stimulation continues to dominate clinical practice, although several non-invasive and alternative modalities are attracting research interest. tDCS and more spatially targeted HD-tDCS seek to reduce cortical excitability, while low-frequency rTMS may be useful for superficial seizure foci. A 2022 systematic review by Simula et al. identified 56 studies of transcranial current stimulation in epilepsy and concluded that tDCS and tACS showed promise, while emphasizing the absence of sufficiently large multicenter studies. Transcutaneous VNS offers lower procedural risk than implanted VNS, but uncertainty remains around nerve engagement, dosing, adherence and blinding. Other investigational approaches include transcranial photobiomodulation, which uses red or near-infrared light to influence cellular energetics and neural activity; low-intensity focused ultrasound, which can direct acoustic energy toward deeper neural targets; and focal cooling, which suppresses neuronal firing and epileptiform propagation by lowering tissue temperature. Evidence remains early, and each modality faces distinct challenges involving target engagement, dosing, reproducibility, and treatment delivery. An open-label study, NCT07145489, is evaluating daily infrared-light treatment in people with epilepsy.
Where the Field Is Heading
Neuromodulation for drug-resistant epilepsy is expanding beyond established VNS, RNS, and DBS systems toward more personalized, adaptive, and less-invasive therapies. Emerging implantable platforms from PRECISIS, Adraxe, Synergia Medical, and iVEAcare are exploring new electrode locations, sensing capabilities, power-transfer methods, and stimulation strategies intended to reduce surgical burden or improve therapeutic precision. If these companies generate compelling clinical evidence and advance toward commercialization, they may become attractive partnership or acquisition candidates for established neuromodulation companies seeking to expand their epilepsy portfolios, consistent with consolidation previously seen in peripheral nerve stimulation and overactive bladder.
Bensalem-Owen identified automated data transfer and rechargeable batteries as two priorities for future systems. “Fully automated uploading of intracranial recordings could reduce the burden of data collection, improve compliance, and support more timely optimization of therapy. Rechargeable batteries could also reduce the need for replacement surgeries and the associated procedural risks.”
Noninvasive approaches—including tDCS, rTMS, transcutaneous VNS, and photobiomodulation—could further broaden access by avoiding surgery. Their principal technical challenge is delivering sufficient and reproducible energy to the intended neural target, particularly when seizure networks are deep, diffuse, or poorly localized. Commercial success will also require convincing clinical evidence, standardized dosing, reliable adherence, practical treatment workflows, reimbursement, and clear differentiation from implantable therapies. Ultimately, patients and clinicians could benefit from less-invasive procedures, broader therapeutic choice and more individualized treatment, provided emerging systems demonstrate meaningful and durable clinical efficacy.
