Objective Novel subcutaneous electroencephalography (sqEEG) systems enable prolonged, near-continuous cerebral monitoring in real-world conditions. Nevertheless, the feasibility, acceptability and overall clinical utility of these systems remains unclear. We report on the longest observational study using ultra long-term sqEEG to date. Methods We conducted a 15-month prospective, observational study including ten adult people with treatment-resistant epilepsy. After device implantation, patients were asked to record sqEEG, to use an electronic seizure diary and to complete acceptability and usability questionnaires. sqEEG seizures were annotated visually, aided by automated detection. Seizure clustering was assessed via Fano Factor analysis and seizure periodicity at multiple timescales was investigated through circular statistics. Results Over a median duration of 438 days, ten patients recorded a median 18.8 hours/day, totalling 71,984 hours of real-world sqEEG data. Adherence and acceptability remained high throughout the study. While 754 sqEEG seizures were recorded across patients, over half (52%) of these were not reported in the patient diary. Of the 140 (27%) diary reports not associated with an identifiable sqEEG seizure, the majority (68%) were reported as seizures with preserved awareness. The sqEEG to diary F1 agreement score was highly variable, ranging from 0.06 to 0.97. Patient-specific patterns of seizure clustering and seizure periodicity were observed at multiple (circadian and multidien) timescales. Interpretation We demonstrate feasibility and high acceptability of ultra long-term (months-years) sqEEG monitoring. These systems help provide real-world, more objective seizure counting compared to patient diaries. It is possible to monitor individual temporal fluctuations of seizure occurrence, including seizure cycles.

JDH is an employee of UNEEG medical A/S. DF is a shareholder of Seer Medical. BHB has equity in Cadence Neurosciences and has received research devices from Medtronic Inc. at no cost, and has received research support from UNEEG and Neurelis. MPR has been a member of ad-hoc advisory boards for UNEEG medical A/S. PFV has received travel and consultancy fees from UNEEG Medical A/S. No other authors have conflicts to declare.

This work was supported by the Epilepsy Foundation Epilepsy Innovation Institute My Seizure Gauge Project. MPR is supported by the NIHR Biomedical Research Centre; the MRC Centre for Neurodevelopmental Disorders (MR/ N026063/1). BHB was supported by the NIH NINDS (UG3 NS123066).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics Committee/IRB of London/Bromley Research Ethics Committee gave ethical approval for this work (19/LO/0354)

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data from selected subcutaneous EEG recordings that support these findings will be made available in a future open-source seizure prediction challenge.