High Definition Cathodal transcranial direct current stimulation successful for Acute Ischemic Stroke

New research revealed that High-definition cathodal direct current stimulation (HD C-tDCS) is a feasible and tolerable treatment for acute ischemic stroke (AIS) patients ineligible for reperfusion treatment. There were beneficial effects on penumbral salvage, hypoperfusion region, and quantified relative cerebral blood volume (qrCBV). The trial results were published in JAMA Network Open.

Acute ischemic stroke (AIS) is the leading cause of death and disability globally. Present treatment options are restricted to reperfusion therapies: intravenous thrombolysis and endovascular thrombectomy. Due to a relatively low outcome rate, additional therapies have been developed. Past literature showed the preclinical models of cathodal transcranial direct current stimulation (C-tDCS) providing neuroprotection for acute ischemic stroke (AIS) by inhibiting peri-infarct excitotoxic effects and enhancing collateral perfusion due to its vasodilatory properties. Hence researchers conducted a randomized clinical trial to report the first-in-human pilot study using individualized high-definition (HD) C-tDCS as a treatment of AIS.

The trial was sham-controlled with a 3 + 3 dose escalation design, was conducted at a single center from October 2018 to July 2021, and participants were followed for 90 days. The inclusion criteria were those treated for AIS within 24 hours from the onset, had imaging evidence of cortical ischemia with salvageable penumbra, and were ineligible for reperfusion therapies. HD C-tDCS electrode montage was selected for each patient to deliver the electric current to the ischemic region only. There were 3 Primary outcomes:

Feasibility -as assessed by the duration from randomization to study stimulation initiation

Tolerability- as assessed by the rate of patients completing the full study stimulation period; and

Safety -as assessed by rates of symptomatic intracranial hemorrhage at 24 hours. The efficacy imaging biomarkers of neuroprotection and collateral enhancement were explored.

Key findings:

• Out of 10 enrolled patients with AIS, seven were randomized to active treatment and 3 to sham.
• The mean (SD) age was 75 (10) years. Among them, there were 6 (60%) females, and the National Institutes of Health Stroke Scale score was mean (SD) 8 (7).
• Two doses of HD C-tDCS (1 mA for 20 minutes; 2 mA for 20 minutes) were studied.
• The speed of HD C-tDCS implementation was a median (IQR) of 12.5 minutes (9-15 minutes) in the last 4 patients.
• Patients tolerated the HD C-tDCS with no permanent stimulation cessation.
• The hypoperfused region was reduced by a median (IQR) of 100% in the active group and increased by 325% in the sham.
• Change in quantitative relative cerebral blood volume early poststimulation was a median (IQR) 64% (40% to 110%) in active and −4% (−7% to 1%) sham patients and followed a dose-response pattern.
• Penumbral salvage in the active C-tDCS group was median (IQR) 66% (29% to 80.5%) while it was 0% (IQR 0% to 0%) in sham.

Thus, This is the first human trial that found that HD C-tDCS can be efficiently used in emergency settings.

Further reading: Bahr-Hosseini M, Nael K, Unal G, et al. High-definition Cathodal Direct Current Stimulation for Treatment of Acute Ischemic Stroke: A Randomized Clinical Trial. JAMA Netw Open. 2023;6(6):e2319231. doi:10.1001/jamanetworkopen.2023.19231