Refined Sphenopalatine Ganglion Stimulator Placement and Intensity Setting to Augment Blood Flow and Neurologic Function

Abstract

Background and Purpose- Two large, randomized trials indicated that sphenopalatine ganglion (SPG) stimulation improves final disability outcome in acute anterior circulation patients with ischemic stroke with confirmed cortical involvement. This study evaluated 2 refinements in SPG stimulation treatment technique: (1) SPG electrode placement with real-time optical tracking guidance; and (2) stimulation intensity comfortable tolerance level selection using non-noxious facial physiological markers. Methods- This study was a single, active arm trial at 4 centers, enrolling patients with anterior circulation ischemic stroke, National Institutes of Health Stroke Scale 1 to 6 including arm weakness subitem score ≥1, not receiving recanalization therapies, and within 24 hours of onset. Stimulation level was set based on ipsilateral facial tingling sensation or lacrimation. SPG stimulation effects were assessed by measuring volumetric blood flow in the ipsilateral common carotid artery by ultrasound and grasp and pinch strength in the affected hand before and during stimulation, and by change in National Institutes of Health Stroke Scale from day 1 to 7. Results- Among 50 enrolled patients, age was median 66 years (interquartile range, 60-74), 44% were female, National Institutes of Health Stroke Scale median was 5 (interquartile range, 4-5), and median onset-to-screening time was 18 hours (interquartile range, 9-20). Median implantation skin-to-skin time was 4 minutes (interquartile range, 3-7), and all 50 implants were placed correctly. Comfortable tolerance level was found based on physiological biomarkers in 96% of patients, including 86% in the optimal, low-medium intensity range. SPG stimulation significantly increased common carotid artery peak systolic and end-diastolic blood flow (44%, P<0.0001; and 52%, P<0.0001) and improved pinch strength (42%, P<0.0001) and grasp strength (26%, P<0.0001). Degree of National Institutes of Health Stroke Scale recovery by day 7 was greater than in matched historic controls, median 75% versus 50%, P=0.0003. Conclusions- SPG stimulator placement with real-time optical tracking guidance was fast and accurate, and selection of stimulation intensity levels based on non-noxious facial tingling and lacrimation was feasible in nearly all patients. SPG stimulation led to cervico-cranial blood flow augmentation and improved hand motor function. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03551093.

Keywords: biomarker; collateral circulation; electrode; ganglia; hand strength; nasolacrimal duct; pinch strength.

Figures

Figure 1.

Schematic overview of protocols to determine stimulation intensity comfortable tolerance levels (CTL). A, Protocol used in prior ImpACT-24B trial (Implant for Augmentation of Cerebral Blood Flow Trial B) with escalation to mild facial pain and then de-escalation. Blueline: planned treatment protocol, redline: deviations from treatment protocol observed in 24.9% of patients, who received ongoing stimulation at levels that occasionally evoked facial discomfort and were associated with reduced final disability outcome efficacy. B, Protocol used in current ImpACT-24M (Implant for Augmentation of Cerebral Blood Flow Trial in Mild Strokes) trial with escalation to non-noxious physiological biomarkers of tingling sensation (1) or unilateral lacrimation (2).

Figure 2.

Distribution of attained comfortable tolerance level (CTL) stimulation intensities in ImpACT-24M (Implant for Augmentation of Cerebral Blood Flow Trial in Mild Strokes) and clinical efficacy dose-response curve (for favorable 3-month disability outcome) observed in ImpACT-24B trial (Implant for Augmentation of Cerebral Blood Flow Trial B). Blue bar histogram shows ImpACT-24M CTL stimulation intensities from 0-100% of electrode maximum in bin sizes of 5%. Solid green line shows odds ratios (OR) for favorable 3-month disability outcome at different stimulation intensities in the ImpACT-24B (and dotted lines show 95% CI).

Figure 3.

Effect of sphenopalatine ganglion stimulation on hand strength on affected and nonaffected sides. A, Pinch strength change from baseline to 2 h and change from baseline to 4 h, (B) grasp strength change from baseline to 2 h and change from baseline to 4 h. Error bars indicate the 95% CI of the difference compared with baseline measurement.

Figure 4.

Scatterplots and linear trend lines showing relation between increase in common carotid artery diastolic blood flow volume and hand strength: (A): pinch strength, (B) grasp strength. EDF indicates end-diastolic flow volume.