Welcome to PracticeUpdate! We hope you are enjoying temporary access to this content.
Please register today for a free account and gain full access
to all of our expert-selected content.
Already Have An Account? Log in Now
High-Definition Cathodal Direct Current Stimulation for the Treatment of Acute Ischemic Stroke
TAKE-HOME MESSAGE
- This proof-of-concept study tested cathodal (inhibitory) transcranial direct current stimulation (tDCS) in patients (N = 10) with acute ischemic stroke and salvageable tissue who were not candidates for reperfusion therapies. tDCS application in the acute setting was feasible and well-tolerated by the patients. Cathodal tDCS stimulation was associated with a reduction in hypoperfused tissue and an increase in cerebral blood volume compared with sham stimulation.
- This small study shows that tDCS is safe and feasible in patients with acute ischemic stroke and suggests that tDCS may have a potential neuroprotective effect in the hypoperfused tissue.
abstract
This abstract is available on the publisher's site.
Access this abstract nowIMPORTANCE
Cathodal transcranial direct current stimulation (C-tDCS) provides neuroprotection in preclinical models of acute ischemic stroke (AIS) by inhibiting peri-infarct excitotoxic effects and enhancing collateral perfusion due to its vasodilatory properties.
OBJECTIVE
To report the first-in-human pilot study using individualized high-definition (HD) C-tDCS as a treatment of AIS.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial was sham controlled with 3 + 3 dose escalation design, and was conducted at a single center from October 2018 to July 2021. Eligible participants were treated for AIS within 24 hours from 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. Patients were followed for 90 days.
MAIN OUTCOMES AND MEASURES
Primary outcomes were feasibility, assessed as time from randomization to study stimulation initiation; tolerability, assessed by rate of patients completing the full study stimulation period; and safety, assessed by rates of symptomatic intracranial hemorrhage at 24 hours. The efficacy imaging biomarkers of neuroprotection and collateral enhancement were explored.
RESULTS
A total of 10 patients with AIS were enrolled, 7 were randomized to active treatment and 3 to sham. Patient age was mean (SD) 75 (10) years old, 6 (60%) were female, and National Institutes of Health Stroke Scale score was mean (SD) 8 (7). Two doses of HD C-tDCS (1 milliamp [mA] for 20 minutes and 2 mA for 20 minutes) were studied. The speed of HD C-tDCS implementation was a median (IQR) 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) 100% (46% to 100%) in the active group vs increased by 325% (112% to 412%) in sham. Change in quantitative relative cerebral blood volume early poststimulation was a median (IQR) 64% (40% to 110%) in active vs -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%) vs 0% (IQR 0% to 0%) in sham.
CONCLUSION AND RELEVANCE
In this randomized, first-in-human clinical trial, HD C-tDCS was started efficiently and well tolerated in emergency settings, with signals of beneficial effect upon penumbral salvage. These results support advancing HD C-tDCS to larger trials.
Additional Info
Disclosure statements are available on the authors' profiles:
High-definition Cathodal Direct Current Stimulation for Treatment of Acute Ischemic Stroke: A Randomized Clinical Trial
JAMA Netw Open 2023 Jun 01;6(6)e2319231, M Bahr-Hosseini, K Nael, G Unal, M Iacoboni, DS Liebeskind, M Bikson, JL SaverFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Brain stimulation techniques such as transcranial direct current stimulation (tDCS) or vagal nerve stimulation are not new to the field of stroke neurology, as they have been used to enhance neuroplasticity and promote recovery in patients with subacute to chronic stroke for a while now.1,2 However, after encouraging results in preclinical studies,3 the experimental use of tDCS was recently extended to a novel indication: neuroprotection in humans with hyperacute stroke. Provost-Robieux and colleagues previously tested cathodal tDCS in patients with acute ischemic stroke to determine whether the inhibitory effects of tDCS can mitigate the excitotoxicity in acutely injured brain tissue and improve outcomes. Although the main results of the trial failed to show the benefit of tDCS, the subgroup analysis revealed a trend toward a reduction in infarct growth in patients with large-vessel occlusion.4 Bahr-Hosseini and colleagues nicely build on this previous study by selecting a patient population with clear imaging evidence of hypoperfused tissue rather than applying tDCS for any type of ischemic stroke. Additionally, they target the patients who are ineligible for reperfusion therapies, a group of patients to whom we have very little to offer in the hyperacute stage. Similar to the previous study, this study also shows that tDCS is safe and feasible in the hyperacute stroke setting. Exploration of the efficacy outcomes yielded a pleasant surprise, which was a better profile of restoration of the blood flow in the penumbra. Of note, the study was underpowered owing to a very small sample size (7 active and 3 sham stimulation procedures), and the statistical analysis was primarily descriptive in nature.
We are potentially in the dawn of an exciting era in stroke neuromodulation research. Noninvasive brain stimulation emerges as a new target for neuroprotective therapy to preserve the penumbra in patients with hyperacute/acute ischemic stroke. Although the mechanism underlying this potential benefit is not entirely clear, the favorable effect of tDCS on local flow dynamics is the leading hypothesis. Further phase II and III randomized and sham-controlled clinical trials are needed to investigate the efficacy of tDCS for hyperacute ischemic stroke.
References