Abstract WP36: Transcranial Electrical Stimulation (tdcs) In Stroke Early After Onset Clinical Trial (tesseract)

Abstract

Background: In preclinical studies of acute ischemic stroke (AIS), cathodal transcranial direct current stimulation (C-tDCS) provides neuroprotection by inhibiting peri-infarct depolarization, apoptotic and inflammatory cascades, and by enhancing collateral perfusion. We undertook the first-in-human feasibility study of high-definition (HD) C-tDCS as an individualized treatment strategy in AIS. Method: The study design was a randomized, sham-controlled, 3+3 dose-escalation feasibility trial. Key entry criteria were patients within 24hr from AIS onset, imaging evidence of cortical-supplying vessel occlusion and substantial penumbra, and ineligibility for reperfusion therapies. HD C-tDCS was delivered to the penumbra using individualized montages. Current flow models showed the specificity of electrical field coverage to ischemic regions. Results: Among 10 enrolled patients, 7 were allocated to active C-tDCS and 3 sham. Age in active/sham patients was 75 (±19.6) vs 77 (±12); entry NIHSS in active/sham patients was 8 (±8.5) vs 7(±2.6). The first 4 patients (3 active and 1 sham) received 1mA-20min (Tier1) and the subsequent 6 (4 active and 2 sham) 2mA-20min (Tier2) of C-tDCS. All patients completed the stimulation with no significant intolerability. C-tDCS met the study primary feasibility endpoint, with speed of tDCS implementation median 12.5 min (IQR 9-15) in the last 4 patients. One symptomatic intracranial hemorrhage occurred due to a ruptured mycotic aneurysm for which Tier 2 was extended. Median penumbral salvage proportion in the active C-tDCS group was 66% (IQR 29-80.5) compared to 0% (IQR 0-0) in sham. Recanalization rate was 83% in active vs 33% in sham (Figure). Conclusion: High-definition C-tDCS is a feasible non-invasive targeted treatment for AIS and showed strong signals of beneficial effects upon penumbral salvage and vessel recanalization. These data warrant conduct of large efficacy and safety trials of C-tDCS as an AIS therapy.