Bornstein NM, et al. - Through ImpACT-24B, a randomized, double-blind, sham-controlled, pivotal trial conducted at 73 centers in 18 countries with 1,078 men aged 40–80 years and women aged 40–85 years with anterior-circulation acute ischemic stroke not having reperfusion therapy, researchers assessed if functional outcome could be improved with sphenopalatine ganglion stimulation 8–24 hours following acute ischemic stroke. Subjects were randomized into either the intervention or the sham-control group. A total of 1,000 subjects received at least one session of sphenopalatine ganglion stimulation or sham stimulation and entered the modified intention-to-treat (mITT) population; 520 (52%) of them had validated cortical involvement (CCI) on imaging. In the CCI population, an inverse U-shaped dose-response association between attained sphenopalatine ganglion stimulation intensity and the primary outcome was noted and at low–midrange intensity. The proportion with favorable outcome progressed from 40% to 70% and was reduced back to 40% at high-intensity stimulation. No variations in mortality or serious adverse events between the intervention group (n=536) and the sham control group (n=519) in the safety population could be ascertained. For patients with acute ischemic stroke who are ineligible for thrombolytic therapy, sphenopalatine ganglion stimulation was concluded to be safe8–24 hours following onset. Sphenopalatine ganglion stimulation could improve functional outcome in patients who have imaging evidence of cortical involvement at presentation, however, it did not reach the significance.