Second Exemplar of a Transcranial Electrical Stimulation in Stroke Early After Onset Clinical Trial Patient
left MCA-M2 occlusion, hyperintensity, hyperintensities, stroke, inferior division occlusion, AIS, rash, SICH, skin burning, hypoperfusion of the parieto-temporal region, acute ischemic stroke, septic, infarction
ACUTE INFARCT, STROKE, HYPOPERFUSION, RECRUITMENT, SECONDARY, INFARCTION
Patient 2 was a female in her 70s with acute ischemic stroke (AIS) due to left middle cerebral artery (MCA) inferior division occlusion. She received 20 minutes of 1 milliamp (mA) high-definition (HD) cathodal transcranial direct current stimulation to the left parieto-temporal region. Early alleviation of hypoperfusion region, enhancement of relative cerebral blood volume, and recanalization were observed on the stimulated side.A, Acute infarction of the left parieto-temporal region (diffusion-weighted image [DWI] hyperintensity); hypoperfusion of the parieto-temporal region (time-to-maximum [Tmax] >6 seconds); normal to low left parieto-temporal relative cerebral blood volume (rCBV); left MCA-M2 occlusion. B, A selection of MCA-inferior division HD montage with current model predicting the e-field concentration over the ischemic region. C and D, Evolving left parieto-temporal acute infarct (DWI hyperintensities); early and sustained alleviation of hypoperfusion; early and sustained rCBV enhancement of the stimulated site; early and lasting left MCA-M2 partial recanalization. MRI indicates magnetic resonance imaging.The speed of HD C-tDCS implementation was a median (IQR) 12.5 minutes (9-15 minutes) in the last 4 enrolled patients. The primary tolerability end point was met with all patients completing the assigned stimulation period. For the secondary tolerability end point, no discoloration or rash was detected on skin visual inspection after the stimulation. Only 1 tier 1 patient complained of mild skin burning, which was alleviated after a short pause of the stimulation.One SICH occurred in 1 active patient at tier 2 of the study who was later determined to be a protocol deviation for not having fully met the entry criteria (stroke due to septic embolization). Nonetheless, tier 2 of the study was extended to enroll more patients. As recruitment was slower than expected, related to the COVID-19 pandemic, the study was stopped after enrollment of the 10th patient (eTable 4 in In the per-protocol exploratory efficacy analysis, imaging biomarkers of neuroprotection and collateral enhancement were characterized in 5 active patients and 3 sham patients, early and late poststimulation. The exploratory per protocol analysis of imaging end points excluded 2 active group patients with protocol deviations: 1 patient with no penumbra present at baseline on imaging core review and 1 with septic embolization as stroke cause.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 qrCBV early poststimulation was a median (IQR) 64% (40% to 110%) in active vs −4% (−7% to 1%) in sham patients. Penumbral salvage in the active C-tDCS group was a median (IQR) 66% (29% to 80.5%) compared with 0% (IQR 0% to 0%) in sham. For the imaging biomarker of collateral enhancement (qrCBV), the response was consistent with a dose-response effect, highest at tier 2, intermediate at tier 1, and lowest at sham (