Transcranial Direct Current Stimulation to Treat Focal Status Epilepticus: A Controlled Pilot Trial - 7. ABSTRACT Transcranial direct current stimulation (tDCS) is non-invasive, affordable, safe, portable and thus a good candidate for bedside use in a critical care setting. The overall aim of this proposal is to develop a novel treatment for refractory definite or probable focal status epilepticus in the critical care setting, using tDCS. In the first year (UG3 phase), a pilot study in 12 total subjects at the participating sites will demonstrate tolerability of tDCS, better define the optimal current (mA) dose and timing of tDCS, ability to collect relevant physiologic data and show a trend towards efficacy. In the subsequent four years of a four-center (Stanford, Mayo, Barrow Neurological Institute, Cleveland Clinic), randomized, blinded, placebo-controlled trial on 100 subjects, we will demonstrate safety, tolerability and ability of tDCS to reduce electrographic and clinical seizures. Eligible candidates will be men or non-pregnant women ages 18 and older, with refractory focal status epilepticus or the electroencephalographic equivalent, and no more than two seizure foci. The UH3 trial design will be a four-centered phase II, randomized, blinded trial of safety and efficacy of tDCS for focal status epilepticus. Subjects will be randomized, 50 to active and 50 to sham tDCS as optimized in the UG3 phase, followed if necessary, by open- label active stimulation beginning 48 hours after the last tDCS session. Each stimulation session will employ parameters suggested by the UG3 phase, in the range of 0.5-4 mA cathodal stimulation at the scalp over the spike/seizure focus for 30 minutes x 2 per day, repeated for 2 or 3 consecutive days. All other medications and therapies will be at discretion of the treatment team. The primary outcome variables will be reduction of time spent in electrographic seizures (seizure burden), compared to baseline in the active versus sham stimulation group and safety/tolerability of the treatment. Secondary outcome variables will include EEG spike and seizure counts, time in ICU, on anesthetics from time of randomization and Rankin functional scale at discharge. We will show that tDCS reduces network connectivity of the seizure focus to other regions of brain and improves regional cerebral blood flow produced by prolonged status. Outcomes will assist planning of a definitive Phase III trial by showing a likely efficacy effect - its time of onset and duration, identifying subgroups likely to respond best and validating stimulation and study procedures. This project will open exploration of a new avenue of therapy for refractory and health-endangering focal status epilepticus by transcranial direct current stimulation.
