A Pilot Study of High-Definition Transcranial Direct Current Stimulation in Refractory Status Epilepticus: The SURESTEP Trial

Refractory status epilepticus (RSE) is a life-threatening emergency with high mortality and poor functional outcomes in survivors. Treatment is typically limited to intravenous anesthetic infusions and multiple anti-seizure medications. While ongoing seizures can cause permanent neurological damage, medical therapies also pose severe and life-threatening side effects. We tested the feasibility of using high-definition transcranial direct current stimulation (hd-tDCS) in the treatment of RSE. We conducted 20-min hd-tDCS sessions at an outward field orientation, intensity of 2-mA, 4 + 1 channels, and customized for deployment over the electrographic maximum of epileptiform activity (“spikes”) determined by real-time clinical EEG monitoring. There were no adverse events from 32 hd-tDCS sessions in 10 RSE patients. Over steady dosing states of infusions and medications in 29 included sessions, median spike rates/patient fell by 50% during hd-tDCS on both automated ( p = 0.0069) and human ( p = 0.0277) spike counting. Median spike rates for any given stimulation session also fell by 50% during hd-tDCS on automated spike counting ( p = 0.0032). Immediately after hd-tDCS, median spike rates/patient remained down by 25% on human spike counting ( p = 0.018). Compared to historical controls, hd-tDCS subjects were successfully discharged from the intensive care unit (ICU) 45.8% more often ( p = 0.004). When controls were selected using propensity score matching, the discharge rate advantage improved to 55% ( p = 0.002). Customized EEG electrode targeting of hd-tDCS is a safe and non-invasive method of hyperacutely reducing epileptiform activity in RSE. Compared to historical controls, there was evidence of a cumulative chronic clinical response with more hd-tDCS subjects discharged from ICU.