After 6 months of stimulation, more than half (53%) of patients with drug-resistant epilepsy were responders to treatment with at least a 50% reduction in seizure frequency.
Recently published findings from 2 nonrandomized uncontrolled trials showed that epicranial focal cortex stimulation (FCS) with the EASEE device (Precisis), a minimally invasive brain pacemaker, was associated with a significant reduction in the frequency of seizures in drug-resistant focal epilepsy. These data served as the basis for the CE certification of EASEE, which occurred in September 2022.1,2
Published in JAMA Neurology, the study was a pooled analysis of EASEE II (DRKS00015918) and PIMIDES I (DRKS00017833), 2 first in-human, prospective, single-arm trials with an 8-month evaluation period. A total of 33 individuals with drug-resistant focal epilepsy received the neurostimulation device implant following a 1-month prospective baseline period. After a 1-month postimplantation recovery period, unblinded FCS was activated using both high-frequency and direct current (DC)-like components performed via electrode arrays placed epicranially above the individual epileptic focus region.
Patients were between 18 and 75 years, with focal-onset seizures uncontrolled by at least 2 antiseizure medications. The most common ASMs used were lamotrigine (n = 16), brivaracetam (n = 13), levetiracetam (n = 9), and perampanel (n = 6). Led by Andreas Schulze-Bonhage, MD, head of the Epilepsy Center at the University Hospital Freiburg, patients were asked to complete the Quality of Life in Epilepsy-Problems (QOLIE-31-P) questionnaire, the Seizure Severity Questionnaire (SSQ), and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E).
In total, 32 individuals underwent combined high-frequency direct current-like stimulation at least until the 8-month postimplant follow-up visit. The primary end point, a treatment response defined as a 50% reduction in seizure frequency, was achieved by 17 of the 32 participants (53.1%) at 6 months. Additionally, 4 of the 32 individuals (12.5%) had no seizures in the sixth month of active stimulation. The therapy continued to show greater efficacy as time went along, and all 6 of the early responders during the first 3 months of FCS treatment remained responders in the subsequent 3 months.
"Implantation of the novel neurostimulation device was tailored to each of the study patients with the electrode positioned epicranially according to the location of the respective predominant epileptic focus," Schulze-Bonhage et al wrote. "Additional data are needed to evaluate if antiseizure outcomes associated with epicranial stimulation are limited to foci on the dorsolateral convexities or also extend to deep foci via network effects."
In terms of safety, there were no deaths, and no adverse events (AEs) that led to discontinuation of treatment. During the first 8 months, 11 serious AEs were reported in 7 of the 33 participants (21.1%); however, non of them were considered associated with the device or procedure. At 4 months after device implantation, the absence of device-or procedure-associated serious AEs was within a 95% CI of 0% to 10.58%.
Most of the cohort (75.6%) had AEs associated with device implantation, although most were either mild or moderate in severity, and 80% of AEs were resolved by month 8. Of the 7 patients (21.2%) who experienced headaches, 5 experienced these events within 30 days after device implantation. Device associated events were reported in 5 of the 33 participants (15.2%), with 1 patient each reporting administration site dysesthesia, implant site pruritus, device site discomfort, incision site complication, wound pain, headache, and scar pain.
Two patients experienced worsening of seizures throughout the trial. Additionally, 2 patients experienced status epilepticus during the trial, 1 of which had a history of status epilepticus and ASM tapering before entering the study. The other patient had never received stimulation with the study device due to the presence of metal implants in the skull. Psychiatric symptoms were found in 2 patients, both with depressive symptoms. One patient had worsening of a preexisting condition while the other had symptoms attributed to COVID-19 pandemic restrictions.
"Epicranial FCS has low invasiveness, and results suggest a remarkably positive safety profile,” the study investigators wrote. “The extracranial positioning of the neurostimulation device electrode avoids risks of (1) intracranial hemorrhage with intracranial stimulation and (2) unwanted effects of vagus nerve lesioning or stimulation. Unlike VNS (vagus nerve stimulation), FCS from a subgaleal position remains unperceived by patients when appropriate stimulation intensities are chosen and is also imperceptible to others. The tunneling procedure connecting the pulse generator to the lead is similar to that in VNS and DBS."
Mood, assessed by NDDI-E, showed no changes following treatment with EASEE, demonstrated by mean scores of 13.0 (SD, 1.2) at baseline ant 13.3 (SD, 1.2) at 8-month follow-up visit. Cognition, evaluated through the EpiTrack tool, showed a trend toward improvement, with mean scores of 27.7 (SD, 2.2) at baseline and 29.1 (SD, 2.1) at 8-month follow-up (mean change, +1.30; P <.10).