Focal Cortex Stimulation With a Novel Implantable Device and Antiseizure Outcomes in 2 Prospective Multicenter Single-Arm Trials

Abstract

ImportanceFor the large population of people with drug-refractory epilepsy, alternative treatment approaches are needed. Clinical trial outcomes of a novel stimulation device, which is newly available in Europe for the treatment of patients with a predominant seizure focus, are reported for the first time.ObjectiveTo perform a pooled analysis of the results of 2 prospective, multicenter, single-arm trials, A Pilot Study to Assess the Feasibility of Neurostimulation With the EASEE System to Treat Medically Refractory Focal Epilepsy (EASEE II) and A Pilot Study to Assess the Feasibility of Patient-Controlled Neurostimulation With the EASEE System to Treat Medically Refractory Focal Epilepsy (PIMIDES I), assessing the safety and efficacy of epicranial focal cortex stimulation (FCS) with a novel implantable device (EASEE [Precisis]) as adjunctive treatment for adult patients with drug-refractory focal epilepsy.Design, Setting, and ParticipantsThis study was a pooled analysis of 2 nonrandomized uncontrolled trials, EASEE II and PIMIDES I, which began on January 15, 2019, and January 14, 2020, respectively, and ended on July 28, 2021. EASEE II and PIMIDES I were the first in-human, prospective, single-arm trials with an 8-month evaluation period. Patients were recruited at 7 European epilepsy centers. Consecutive participants with drug-refractory focal epilepsy were enrolled. Study data were analyzed from September 29, 2021, to February 2, 2022.InterventionsAfter a 1-month prospective baseline period, patients were implanted with the neurostimulation device. 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.Main Outcomes and MeasuresEfficacy was prospectively assessed by the responder rate in the sixth month of stimulation compared with baseline; safety and additional end points were assessed after device implantation and during the stimulation period.ResultsOf the 34 adult patients enrolled at 6 German and 1 Belgian investigational site, 33 (mean [SD] age, 34.6 [13.5] years; 18 male patients [54.5%]) received the neurostimulation device implant. A total of 32 patients underwent combined high-frequency direct current–like stimulation at least until the 8-month postimplant follow-up visit. After 6 months of stimulation, 17 of 32 patients (53.1%) were responders to treatment with at least a 50% reduction in seizure frequency compared with baseline, corresponding to a significant median seizure reduction by 52% (95% CI, 0.37%-0.76%; P < .001). No device- or procedure-related serious adverse events were reported (0; 95% CI, 0%-10.58%). There were no significant alterations in cognition, mood, or overall quality of life.Conclusions and RelevanceResults of this pooled analysis of 2 nonrandomized uncontrolled trials suggest that FCS with a novel neurostimulation device was associated with an effective reduction in seizure frequency in patients with drug-refractory focal epilepsy and may offer a promising treatment option for patients with a predominant epileptic focus.Trial RegistrationGerman Clinical Trials Register: DRKS00015918 and DRKS00017833, respectively, and jointly under PROSPERO: CRD42021266440

Value of ultralong‐term subcutaneous EEG monitoring for treatment decisions in temporal lobe epilepsy: A case report

“…15,16 A correct lateralization of at least the predominant side of seizure generation is, however, a prerequisite for resective epilepsy surgery, laser-based thermocoagulation 17 or epicranial Focal Cortex Stimulation. 14 Whereas the unilateral implantation used here could be based on prior imaging and EEG findings, other patients in whom lateralization of seizures is more unclear may particularly profit from future devices for ultralong-term monitoring presently under investigation. 15,18 The case here shows that in patients in whom additional converging evidence is needed, a unilateral implantation may already provide relevant information which can contribute to decisions in favor of a focal intervention, as offered here in the form of a two-thirds anterior temporal lobe resection.…”

“…Overall, this supported the decision in favor of alternative, non‐pharmacological treatment approaches. This can be epilepsy surgery 10 or neuromodulatory treatment approaches (eg, VNS, 11 DBS, 12 RNS, 13 or FCS 14 ).…”

“…Short durations of in‐patient monitoring have been shown to considerably undersample seizures and may provide insufficient information on the lateralization of seizure origin 15,16 . A correct lateralization of at least the predominant side of seizure generation is, however, a prerequisite for resective epilepsy surgery, laser‐based thermocoagulation 17 or epicranial Focal Cortex Stimulation 14 . Whereas the unilateral implantation used here could be based on prior imaging and EEG findings, other patients in whom lateralization of seizures is more unclear may particularly profit from future devices for ultralong‐term monitoring presently under investigation 15,18 .…”

Add‐on treatment with cenobamate is already effective at low doses in refractory focal epilepsy: A prospective observational study

“…Among the entire patient cohort (n = 112), 13% of patients (14/112) had cenobamate withdrawal due to AEs, and 4% (5/112) due to lack of efficacy. Three patients underwent nonpharmacological interventions during the study period, including focal cortex stimulation (1/112) 17 and surgical treatment (2/112). The available data of these patients were included in the study only for the time period prior to nonpharmacological intervention.…”

Exploring the Potential of Transcranial Direct Current Stimulation for Relieving Central Post-Stroke Pain: A Randomized Controlled Pilot Study

“…These techniques stimulate the activity of neural network-related areas by releasing weak electrical currents or magnetic fields into the scalp. In addition, the stimulation selectively affects the activity of sodium and calcium ion channels in the local brain region [ 24 , 25 , 26 ].…”