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

Saver, Jeffrey L.; Kharaishvili, Nino; Janelidze, Tamar; Beridze, Maia; Zarqua, Natia; Solberg, Yoram; Bornstein, Natan M.

doi:10.1161/strokeaha.119.027177

Cited by 7 publications

(7 citation statements)

References 20 publications

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“…The 49 patients that received stimulation demonstrated a median NIHSS improvement of 75% compared to 50% in the historical control. Stimulation was also shown to significantly increase CBF and hand motor function within the cohort, but was not compared to the historical control ( 63 ).…”

Section: Resultsmentioning

confidence: 96%

“…The ImpACT24M study, reported by Saver et al ( 63 ), was a single-arm study assessing the effect of two changes to the SPG stimulation procedure required for implanting and optimizing the device. Primary outcomes were difference in 7-day NIH Stroke Scale (NIHSS), and proportion of patients with improvement in stroke symptoms, compared to historical controls ( 65 ).…”

Section: Resultsmentioning

confidence: 99%

“…Four clinical studies using invasive electrical stimulation to treat AIS were identified (Table 5) (60)(61)(62)(63). All four targeted the SPG using an implanted device (ISS, BrainsGate, Israel).…”

Section: Invasive Ganglion Stimulation: Clinical Studiesmentioning

confidence: 99%

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Stimulating the Facial Nerve to Treat Ischemic Stroke: A Systematic Review

et al. 2021

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Acute ischemic stroke (AIS) is a common devastating disease that has increased yearly in absolute number of cases since 1990. While mechanical thrombectomy and tissue plasminogen activator (tPA) have proven to be effective treatments, their window-of-efficacy time is very short, leaving many patients with no viable treatment option. Over recent years there has been a growing interest in stimulating the facial nerves or ganglions to treat AIS. Pre-clinical studies have consistently demonstrated an increase in collateral blood flow (CBF) following ganglion stimulation, with positive indications in infarct size and neurological scores. Extensive human trials have focused on trans-oral electrical stimulation of the sphenopalatine ganglion, but have suffered from operational limitations and non-significant clinical findings. Regardless, the potential of ganglion stimulation to treat AIS or elongate the window-of-efficacy for current stroke treatments remains extremely promising. This review aims to summarize results from recent trial publications, highlight current innovations, and discuss future directions for the field. Importantly, this review comes after the release of four important clinical trials that were published in mid 2019.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

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Stimulating the Facial Nerve to Treat Ischemic Stroke: A Systematic Review

et al. 2021

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“…The mechanism of action in these diseases is blockade of the trigeminovascular network of which the SPG is a component and, more precisely, blockade of the parasympathetic autonomic vasomotor system that is responsible, among other things, for nasal congestion [ 12 ]. In contrast, in stroke, SPG neuromodulation by implanted stimulation targets a stimulant effect on the parasympathetic nervous system [ 36 ] with a demonstrated benefit in terms of increased cerebral blood flow secondary to the release of vasodilator neurotransmitters (Nitric Oxide, acetylcholine), decreased cerebral oedema due to stabilisation of the blood-brain barrier, and potentially a neuroprotective effect [ 37 ]. In particular, it should be noted that high-frequency implanted SPG stimulation induces a reduction of postganglionic parasympathetic activity [ 13 ], while a parasympathetic stimulant effect is observed in response to low-frequency stimulation, with the consequent risk of cluster-like attacks [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Osteopathic Manipulation of the Sphenopalatine Ganglia Versus Sham Manipulation, in Obstructive Sleep Apnoea Syndrom: A Randomised Controlled Trial

Attali

Jacq

Martin

et al. 2021

JCM

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(1) Background: osteopathic manipulation of the sphenopalatine ganglia (SPG) blocks the action of postganglionic sensory fibres. This neuromodulation can reduce nasal obstruction and enhance upper airway stability. We investigated the manipulation of the SPG in 31 patients with obstructive sleep apnoea syndrome (OSAS); (2) Methods: Randomised, controlled, double-blind, crossover study. Participants received active (AM), then sham manipulation (SM), or vice versa. The primary endpoint was apnoea-hypopnoea index (AHI). Secondary endpoints were variation of nasal obstruction evaluated by peak nasal inspiratory flow (PNIF) and upper airways stability evaluated by awake critical closing pressure [awake Pcrit]), at 30 min and 24 h. Schirmer’s test and pain were assessed immediately post-manipulation. Tactile/gustatory/olfactory/auditory/nociceptive/visual sensations were recorded. Adverse events were collected throughout. (3) Results: SPG manipulation did not reduce AHI (p = 0.670). PNIF increased post-AM but not post-SM at 30 min (AM-SM: 18 [10; 38] L/min, p = 0.0001) and 24 h (23 [10; 30] L/min, p = 0.001). There was no significant difference on awake Pcrit (AM-SM) at 30 min or 24 h). Sensations were more commonly reported post-AM (100% of patients) than post-SM (37%). Few adverse events and no serious adverse events were reported. (4) Conclusions: SPG manipulation is not supported as a treatment for OSAS but reduced nasal obstruction. This effect remains to be confirmed in a larger sample before using this approach to reduce nasal congestion in CPAP-treated patients or in mild OSAS.

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“…Hand pinch and grasp strength improved in parallel with degree of cervico-cranial blood flow improvement. 30 Indirect evidence suggests that CBF increase via collateral enhancement also contributed to the 3 m global disability benefit of SPG-Stim observed in the combined ImpACT-24A and ImpACT-24B trials. SPG-Stim benefit was confined to the confirmed cortical infarct (CCI) population, who had features at entry that would predispose to greater benefit from CBF enhancement, including: (1) NIHSS 10, selecting for patients with persisting large vessel occlusion who are more likely to have penumbral tissue still present beyond 6 h post-onset; and (2) hypodensity in one or more cortical regions, selecting for patients with superficial strokes in whom leptomeningeal collaterals play a more important role in vascular supply.…”

Section: Mechanisms Of Action Of Spg Stimulation (Figure 3)mentioning

confidence: 99%

Mechanisms of action of acute and subacute sphenopalatine ganglion stimulation for ischemic stroke

Hosseini

Saver

2020

International Journal of Stroke

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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 neurovascular and neurobiologic mechanisms of action mediating benefit of SPG-Stim in acute ischemic stroke. Summary of review Located posterior to the maxillary sinus, the SPG is the main source of parasympathetic innervation to the anterior circulation. Preclinical and human studies delineate four distinct mechanisms of action by which the SPG-Stim may confer benefit in acute ischemic stroke: (1) collateral vasodilation and enhanced cerebral blood flow, mediated by release of neurotransmitters with vasodilatory effects, nitric oxide, and acetylcholine, (2) stimulation frequency- and intensity-dependent stabilization of the blood–brain barrier, reducing edema (3) direct acute neuroprotection from activation of the central cholinergic system with resulting anti-inflammatory, anti-apoptotic, and anti-excitatory effects; and (4) neuroplasticity enhancement from enhanced central cholinergic and adrenergic neuromodulation of cortical networks and nitrous oxide release stimulating neurogenesis. Conclusion The benefit of SPG-Stim in acute ischemic stroke is likely conferred not only by potent collateral augmentation, but also blood–barrier stabilization, direct neuroprotection, and neuroplasticity enhancement. Further studies clarifying the relative contribution of these mechanisms and the stimulation protocols that maximize each may help optimize SPG-Stim as a therapy for acute ischemic stroke.

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

Abstract: Supplemental Digital Content is available in the text.

Cited by 7 publications

References 20 publications

Stimulating the Facial Nerve to Treat Ischemic Stroke: A Systematic Review

Stimulating the Facial Nerve to Treat Ischemic Stroke: A Systematic Review

Osteopathic Manipulation of the Sphenopalatine Ganglia Versus Sham Manipulation, in Obstructive Sleep Apnoea Syndrom: A Randomised Controlled Trial

Mechanisms of action of acute and subacute sphenopalatine ganglion stimulation for ischemic stroke

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