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BACKGROUND Sphenopalatine ganglion stimulation (SPG-Stim) for ischemic stroke, starting 8-24 h after onset and continuing through five days in a pooled analysis of two recent, randomized, sham-controlled trials, improved outcome of acute ischemic stroke patients with confirmed cortical involvement. As a neuromodulatory therapy, SPG-Stim differs substantially from existing pharmacologic (lytic and antiplatelets) and device (endovascular thrombectomy) acute ischemic stroke treatments. AIM Focused review of SPG anatomy, physiology, and ne