Transcranial Electrical Stimulation in Stroke EaRly After onset Clinical Trial (TESSERACT)

Abstract Background: Cathodal transcranial direct current stimulation (C-tDCS) provides neuroprotection in preclinical models of acute ischemic stroke (AIS) by inhibiting peri-infarct depolarization, and it enhances collateral perfusion due to its vasodilatory properties. We undertook the first-in-human feasibility study of high-definition (HD) C-tDCS as an individualized treatment strategy in AIS. Methods: The study design was a randomized, sham-controlled, 3+3 dose-escalation. Key entry criteria were patients within 24 hr from AIS onset, imaging evidence of cortical vessel occlusion and substantial penumbra, and ineligibility for reperfusion therapies. HD C-tDCS was delivered to the penumbra using individualized montages with current flow models showing the specificity of the electrical field coverage to ischemic regions. Results: Among 10 enrolled patients, 7 were allocated to active C-tDCS and 3 sham. Age was mean 75 (±19.6) in active vs 77 (±12) in sham patients; entry NIHSS was mean 8 (±8.5) in active vs 7(±2.6) in sham. The first 4 patients (3 active and 1 sham) received 1 mA-20 min (Tier1) and the subsequent 6 (4 active and 2 sham) 2 mA-20 min (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 in the last 4 patients. One symptomatic hemorrhage occurred due to a ruptured mycotic aneurysm for which Tier 2 was extended. Median penumbral salvage proportion in the active group was 66% (IQR 29-80.5) compared to 0% (IQR 0-0) in sham (Figure). Recanalization rate was 83% in active vs 33% in sham. Conclusion: High-definition C-tDCS is a targeted sub-threshold inhibitory treatment strategy that can be feasibly applied in AIS patients and showed strong signals of beneficial effects upon penumbral salvage and vessel recanalization. These data warrant conduct of large efficacy and safety trials of HD C-tDCS as an AIS therapy. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: Acute stroke treatment , Neuroprotection, Collateral enhancement , High-definition tDCS