From Seconds to Seasons: First-in-Human Insights from a Chronic Subscalp EEG System

Abstract

Objective: Patient self-report is known to be an inaccurate reflection of true seizure frequency in persons with epilepsy. The current study aimed to assess the safety and performance of the Minder system, a bilateral subscalp electroencephalographic (EEG) acquisition system for continuous long-term EEG recording. Methods: This prospective, multicenter first-in-human study enrolled adult patients with focal or generalized epilepsy and at least 2 seizures per month. The primary outcome was adverse events (AEs) in the first 6 months of implantation. Secondary analyses determined whether normal neurophysiological signals, interictal discharges, and seizures seen on scalp video EEG monitoring were identifiable on subscalp recordings, and signals were rated for clarity on subscalp and 2-channel scalp EEG recordings (1 = not recognizable, 5 = clear). Subscalp data were reviewed in relation to events reported in 6-month seizure diaries. Results: Twenty-six subjects were implanted between November 2019 and July 2023. No serious device- or implant procedure-related AEs were reported. The most common device-related AEs were mild or moderate postsurgical pain, headache, or scalp pain/paresthesia (9/26, 35%). All sleep spindles, chewing artifacts, interictal discharges, and electrographic seizures observed on scalp recordings (25 seizures from 8 patients) were identified on subscalp recordings and given higher clarity ratings compared to 2-channel scalp recordings (median seizure clarity rating was 3 for both scalp and subscalp EEG, range = 1-5, P = .0025). Subscalp recordings captured seizures from diverse seizure focus locations, including frontal and mesial temporal seizure foci and hypothalamic hamartoma. Bilateral recording revealed clinically relevant findings not possible with unilateral recordings (6/26 patients, 23%). Findings of potential clinical utility were identified on manual review of 6-month recordings in most patients (23/26, 88%). Significance: This study demonstrates the safety and performance of the Minder bilateral subscalp EEG acquisition system for long-term seizure monitoring in patients with epilepsy. Bilateral hemisphere coverage captured seizures in a diverse patient group and permitted lateralization of events.

Commentary

Continuous ambulatory neurophysiological monitoring has long represented a central aspiration in epilepsy care. Each technological shift, going from prolonged video EEG monitoring (VEM), stereo-EEG monitoring to chronic electrocorticography from responsive neurostimulation devices, has expanded our appreciation of the dynamic behavior of epileptic brain networks. With chronic subscalp EEG, we can now begin to understand epilepsy across extended time, capturing its rhythms and fluctuations as they naturally unfold.

The UMPIRE study provides an early view into the safety profile and the potential contributions of chronic subscalp EEG monitoring with the Minder system. The Minder system includes an implantable electrode connected to a telemetry unit, external wearable transmitter, and a smartphone application. The implant consists of a 253-mm lead in the subgaleal space running posterior to the vertex, recording from 4 contacts arranged as 2 bipolar pairs across each hemisphere. The telemetry unit sits in a postauricular bone well, and EEG signals are sent transcutaneously to the external wearable, which relays data via Bluetooth to the smartphone app for local storage and periodic cloud upload.

The UMPIRE study was a first-in-human multicenter, prospective study that enrolled adults with focal or generalized epilepsy who experienced at least 2 seizures per month. ¹ The foundational purpose of the trial was safety assessment, measured with the primary outcome as adverse events (AEs) in the first 6 months of implantation. Among 26 implanted participants, there were no device-related or procedure-related serious adverse events (SAEs). A total of 23 procedure-related AEs occurred in 12 patients. Nine patients (35%) reported self-limited postoperative pain, headache, or paresthesia. Four patients (15%) experienced one each of wound infection, dehiscence, skin ulceration, or subgaleal hematoma. Most were resolved by the end of the study period and did not require explantation of the device. Overall, the procedure was well-tolerated, though not without risks requiring clinical management. Given subgaleal placement without anchoring, lead migration was a concern; however, the clarity of the 6-month recordings and relatively stable scans were reassuring.

UMPIRE study reports detection of seizures arising from the frontal lobes, mesial temporal structures, posterior cortex, or deeper networks. However, without detailed onset-to-detection timing data, it remains unclear whether the system identifies seizures early enough to support forecasting or real-time alerts. With 4 contacts, the system may record cortical activity that propagates to the recorded region, but its capacity to detect seizure onset will need to be further explored. If the system detects seizures after broad cortical spread, forecasting algorithms may be built on late-phase dynamics rather than authentic preictal biomarkers. This will be presented and analyzed in upcoming studies. Therefore, expanding spatial coverage through additional leads, modified trajectories, or modular configurations may be a future consideration in subscalp EEG, especially if being used for diagnostic exclusion or preictal/early ictal modeling.

Inclusion criteria for the study were 2 clinically apparent and electrographically evident seizures per month. A total of 600 diary-reported seizures were submitted across 23 patients (mean 26 ± 19 seizures per patient, range 2-73). Subscalp EEG was available for 63% (377/600) of these events, and among them, electrographic seizures were identified for 31% (115/377). Concordance varied widely between patients (mean 29% ± 27%, range 0%-100%), and 6 patients had no electrographic changes at any diary-indicated time. With VEM, only 12% of diary events aligned with electrographic seizures. Furthermore, at least one unreported seizure was identified in all 8 patients, and overall, 56% of seizures went unreported (14 of 25; range, 1-4 per patient).

These findings should be interpreted with careful attention to several considerations. First, electroclinical dissociation can occur in 2 directions: clinically evident seizures may lack a clear EEG correlate on subscalp recording, and conversely, electrographic seizures on any modality may produce subtle or absent behavioral change and therefore go unrecognized by patients. Both forms of dissociation have long been documented across monitoring approaches. Second, the sampling and technical constraints of subscalp recordings warrant caution. The system's bilateral spatial coverage is an advancement but necessitates thorough validation across the full spectrum of seizure types before it can be relied upon to confidently exclude events. Such work should span focal and generalized seizures, diverse onset patterns and latencies, varying seizure onset zones, and long-term implantation periods, among other considerations. Certainly, this will be studied and presented with the next phase of studies using subscalp EEG. Third, study-design limitations should be acknowledged. Scalp EEG seizure identification relied initially on Persyst detections with subsequent targeted expert review. While Persyst's utility has largely been as a triage strategy in lower-risk EEG environments, this workflow can still fail to capture some seizures. ² Additionally, during the 6-month ambulatory phase, subscalp EEG review was limited to ±30-min windows surrounding diary entries. Because patients often report seizure times imprecisely, this windowing approach may introduce further misalignment between diary reports and EEG data. More broadly, EEG, whether scalp, intracranial, or subscalp, remains a biomarker, and its interpretation must always be anchored in clinical context. Rather than framing diaries as the bottleneck, the more productive path lies in strengthening patient-centered reporting: improving education around event recognition, designing tools that simplify real-time logging, and combining subjective reports with complementary physiologic data from subscalp EEG.

The UMPIRE study represents a critical step in the evolution of minimally invasive, long-duration EEG monitoring. It demonstrates that bilateral subscalp EEG can be implanted safely, remain stable over months, and provide a continuous data stream capable of capturing physiologic and electrographic events across a wide range of epilepsies. Subscalp EEG monitoring systems take aim at challenges that have long complicated epilepsy care. It may uncover seizures that never make it into the diary, identify events emerging during medication adjustments, lateralize hemispheric dominance of seizure onsets, and may clarify previously “unclassified” episodes. It could reveal how often seizures truly occur, detect events that never materialize during even the longest EMU admissions, and breaks free of the time windows that limit home EEG studies. ³ Importantly, the UMPIRE study documented these real-world applications, demonstrating how patients and clinicians relied on the system for exactly these scenarios in the study's usage table.

Overall, this is a particularly meaningful juncture in the evolution of epilepsy care as the UMPIRE study marks the early steps toward a monitoring paradigm that no longer samples epilepsy in snapshots but observes it as a living, longitudinal process, one that spans seconds to seasons.