High-definition cathodal transcranial direct current stimulation (HD C-tDCS) is a promising approach for treating acute ischemic stroke (AIS), results of a pilot study suggest.
Investigators explored the feasibility and safety of the use of HD C-tDCS for patients presenting in the emergency department (ED) of a level 1 stroke center by randomly assigning patients to receive either tDCS or sham.
"We developed and tested a new approach to treat AIS [that] involves delivering a targeted inhibitory form of electrical current via scalp electrodes only to the brain region affected by stroke," lead author Mersedeh Bahr-Hosseini, MD, assistant clinical professor of neurology and vascular neurologist at UCLA Health, in California, told Medscape Medical News.
"We were able to efficiently apply this treatment in emergency settings, and it was well tolerated," she reported. "Furthermore, patients who received active treatment showed promising improvement, measured by looking at brain scans after treatment."
The study was published online June 21 in JAMA Network Open.
Noninvasive, Individualized
"Treatments for AIS are currently limited to reperfusion therapies: intravenous thrombolysis and endovascular thrombectomy," the authors write.
However, "many acute stroke patients are not candidates for the two main treatments and even among those eligible for those treatments, only an estimated 20% to 30% are disability free 3 months after stroke," Bahr-Hosseini said.
"Therefore, as a stroke neurologist who witnesses the suffering of stroke patients first hand, I've been highly motivated to develop a new noninvasive therapy for acute stroke patients that can be individualized and delivered to the brain region affected by stroke only."
In animal models, C-tDCS has been shown to salvage ischemic tissue at risk of infarction through two means: offering direct neuroprotection by "inhibiting peri-infarct excitotoxic effects, inflammatory and apoptotic pathways" and offering "collateral perfusion enhancement by inducing vasodilation," the authors explain.
Moreover, C-tDCS is "regionally directed therapy that instantly reaches maximum local concentration" and can be "tailored to the ischemic tissue at risk of infarction."
The current proof-of-concept study was the first to assess the use of HD C-tDCS in human beings with AIS and salvageable penumbra in emergency settings.
"True Biological Effect"
The researchers randomly assigned 10 patients with AID (mean [SD] age, 75 [10] years; 60% women; National Institutes of Stroke Scale Score 8 [7]) who were in UCLA's ED within 24 hours of onset to receive either C-tDCS or sham treatment (n = 7 and 3, respectively).
Primary outcomes consisted of feasibility (time from randomization to study simulation initiation); tolerability (rate of patients completing the full study simulation period); and safety (rates of symptomatic intracranial hemorrhage at 24 hours).
Tolerability was assessed via two endpoints: the rate of patients who completed the full study simulation period, and a formal tolerability technician questionnaire.
The researchers also evaluated imaging biomarkers of neuroprotection and collateral enhancement at 2 – 4 hours and 24 – 30 hours post stimulation (early and late times points, respectively).
Two doses of HD C-tDCS were studied: 1 milliamp [mA] for 20 minutes (tier 1) and 2 mA for 20 minutes (tier 2). The first four patients (three active, one sham) were enrolled at tier 1, while the subsequent six (four active, two sham) were enrolled at tier 2.
For the last four patients, the speed of HD C-tDCS implementation was a median (IQR) 12.5 minutes (9 – 15 minutes).
"The primary tolerability endpoint was met, with all patients completing the assigned stimulation period," the authors report. No discoloration or rash was detected by the technician on visual inspection following stimulation.
Imaging biomarkers of neuroprotection and collateral enhancement were obtained in five active and three sham patients at early and late time points. (The other two active patients were excluded, owing to protocol deviations.)
The hypoperfused region was reduced by a median of 100% (46% to 100%) in the active group but increased by 325% (112% to 412%) in the sham group.
The quantitative relative cerebral blood volume change in early poststimulation was a median of 64% (40% to 110%) in active vs −4% (−7% to 1%) in sham patients and "followed a dose-response pattern."
In the active C-tDCS group, the median penumbral salvage was 66% (29% to 80.5%) vs 0% (IQR 0% to 0%) in the sham group.
These findings "indicate a possibly true biological effect of the treatment," Bahr-Husseini said.
A limitation noted by the authors is that the study had originally been designed to address feasibility and tolerability aims but was stopped early owing to slow enrollment related to the COVID-19 pandemic, so it had "insufficient power" to fully address these aims and only was able to "partially explore" the safety endpoint.
Nevertheless, the findings warrant "conduct of larger safety and efficacy trials of HD C-tDCS as an AIS therapy and acute stroke-specific refinements in HD equipment design to further accelerate deployment time," the investigators conclude.
"Profound Clinical Implications"
Commenting for Medscape Medical News, Charles Liu, PhD, MD, director of the Neurorestoration Center, University of Southern California, and professor of neurological surgery, neurology, psychiatry, urology, and surgery, USC Keck School of Medicine, said the authors "should be congratulated in providing the first in-human evidence that a noninvasive form of neuromodulation, tDCS, may have a role in the management of acute ischemic stroke."
Although there has been evidence supporting tDCS in animal models of stroke, demonstrating the potential value of this treatment in human patients with acute ischemic stroke is "very important" and has "clear implications, although it was an exploratory study in a small number of patients," said Liu, who was not involved with the study.
"The early management of acute ischemic stroke remains a profound challenge, with many small centers lacking the resources for invasive interventions available in large centers," he continued. "Clearly, if these results bear out in larger, multicenter trials, with the beneficial signals for penumbral salvage being confirmed, the clinical implications could be profound."
There is no doubt that the "future application of neuromodulation in all of its forms will become more evident in the management of neurological disease and noninvasive strategies that can be easily applied may play a dominant role when time sensitivity is paramount," said Liu.
The study was funded by the American Heart Association. Bahr-Hosseini holds a patent for transcranial electrical stimulation in stroke early after onset. The other authors' disclosures are listed on the original article. Liu reports no relevant financial relationships.
JAMA Netw Open. Published online June 21, 2023. Full text
Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).
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Cite this: Noninvasive Brain Stimulation Promising for Acute Stroke - Medscape - Jun 30, 2023.
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