Yan Hou, MD, PhD
Bornstein NM, Saver JL, Diener HC, Gorelick PB, Shuaib A, Solberg Y, et al.. Sphenopalatine Ganglion Stimulation to Augment Cerebral Blood Flow. A Randomized, Sham-Controlled Trial. Stroke. 2019;50:00-00.
Preclinical studies have demonstrated that sphenopalatine ganglion (SPG) stimulation is a potent method to enhance collateral flow and reduce infarct size in stroke animal models. The ImpACT-24A Investigators performed a sham-controlled, randomized trial to test the efficacy and safety of SPG stimulation as a potential therapy for patients with acute anterior circulation ischemic stroke who are not eligible for reperfusion therapy.
A total of 253 patients with acute anterior circulation ischemic stroke with moderate deficit (median NIHSS of 11) within 24 hours of onset not treated with tPA or thrombectomy either received SPG (n=153) or sham (n=100) stimulation. The primary efficacy outcome is mRS improvement beyond expectation at 90 days, which was defined as an mRS score one or more points better than expected based on a prognostic model. Although SPG stimulation only showed a 9.7% higher rates of mRS improvement beyond expectations in the intention to treat population (SPG vs. sham: 49.7% vs. 40%, odd ratio 1.48, p=0.13); there was a 23% higher rate of mRS improvement beyond expectations in the subgroup of patients with confirmed cortical involvement (SPG vs. sham: 50% vs. 27%, odd ratio 2.7, p=0.03). The different beneficial effects of SPG stimulation between patients with cortical infarcts and deep subcortical infarcts was considered due to more robust collateral arterial networks in superficial leptomeningeal arteries supplying the cortical layers. SPG stimulation was not associated with any increase in serious adverse events, symptomatic intracranial hemorrhage, or mortality. Only two serious adverse events were considered possibly related to the implantation (one epistaxis and one torn extraction).
This randomized trial has several limitations. First, rates of off-target placement of neurostimulators were high initially before introduction of the optical navigation system, which lowered the sample size and power. Second, permissive and induced hypertension as a collateral enhancement technique was usually applied to acute ischemic stroke with high grade large vessel stenosis or occlusion, blood pressure level should be balanced as a baseline clinical characteristic. Third, without advanced diffusion imaging, ASPECT infarct growth score from baseline to day 5 was used to roughly reflect salvaged penumbra, which should be better assessed by comparing the size of penumbra at baseline and infarct on day 5 MRI.
Despite these limitations, this is the first randomized clinical trial to assess SPG stimulation as an alternative therapy in patients with acute ischemic stroke. SPG stimulation within 24 hours of onset is safe and has favorable outcomes particularly in patients with acute ischemic stroke with cortical involvement. The beneficial effect of SPG stimulation can be confirmed in a larger pivotal study with improved technique of implantation and use of diffusion imaging. Given permissive or induced hypertension is noninvasive, it may be worthwhile to compare the efficacy of SPG stimulation and induced hypertension.