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

2020 ◽  
Vol 15 (8) ◽  
pp. 839-848 ◽  
Author(s):  
Mersedeh Bahr Hosseini ◽  
Jeffrey L Saver

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.

2020 ◽  
pp. neurintsurg-2020-015957 ◽  
Author(s):  
John Benson ◽  
Seyed Mohammad Seyedsaadat ◽  
Ian Mark ◽  
Deena M Nasr ◽  
Alejandro A Rabinstein ◽  
...  

BackgroundTo assess if leukoaraiosis severity is associated with outcome in patients with acute ischemic stroke (AIS) following endovascular thrombectomy, and to propose a leukoaraiosis-related modification to the ASPECTS score.MethodsA retrospective review was completed of AIS patients that underwent mechanical thrombectomy for anterior circulation large vessel occlusion. The primary outcome measure was 90-day mRS. A proposed Leukoaraiosis-ASPECTS (“L-ASPECTS”) was calculated by subtracting from the traditional ASPECT based on leukoaraiosis severity (1 point subtracted if mild, 2 if moderate, 3 if severe). L-ASEPCTS score performance was validated using a consecutive cohort of 75 AIS LVO patients.Results174 patients were included in this retrospective analysis: average age: 68.0±9.1. 28 (16.1%) had no leukoaraiosis, 66 (37.9%) had mild, 62 (35.6%) had moderate, and 18 (10.3%) had severe. Leukoaraiosis severity was associated with worse 90-day mRS among all patients (P=0.0005). Both L-ASPECTS and ASPECTS were associated with poor outcomes, but the area under the curve (AUC) was higher with L-ASPECTS (P<0.0001 and AUC=0.7 for L-ASPECTS; P=0.04 and AUC=0.59 for ASPECTS). In the validation cohort, the AUC for L-ASPECTS was 0.79 while the AUC for ASPECTS was 0.70. Of patients that had successful reperfusion (mTICI 2b/3), the AUC for traditional ASPECTS in predicting good functional outcome was 0.80: AUC for L-ASPECTS was 0.89.ConclusionsLeukoaraiosis severity on pre-mechanical thrombectomy NCCT is associated with worse 90-day outcome in patients with AIS following endovascular recanalization, and is an independent risk factor for worse outcomes. A proposed L-ASPECTS score had stronger association with outcome than the traditional ASPECTS score.


2018 ◽  
Vol 10 (12) ◽  
pp. 1132-1136 ◽  
Author(s):  
Dylan N Wolman ◽  
Michael Iv ◽  
Max Wintermark ◽  
Gregory Zaharchuk ◽  
Michael P Marks ◽  
...  

Background and purposeAcute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET).Materials and methodsThis retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location.ResultsTwo hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (κ=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; κ=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; κ=0.830; P=0.529).ConclusionAIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.


2018 ◽  
Vol 128 (2) ◽  
pp. 567-574 ◽  
Author(s):  
Christopher J. Stapleton ◽  
Thabele M. Leslie-Mazwi ◽  
Collin M. Torok ◽  
Reza Hakimelahi ◽  
Joshua A. Hirsch ◽  
...  

OBJECTIVEEndovascular thrombectomy in patients with acute ischemic stroke caused by occlusion of the proximal anterior circulation arteries is superior to standard medical therapy. Stentriever thrombectomy with or without aspiration assistance was the predominant technique used in the 5 randomized controlled trials that demonstrated the superiority of endovascular thrombectomy. Other studies have highlighted the efficacy of a direct aspiration first-pass technique (ADAPT).METHODSTo compare the angiographic and clinical outcomes of ADAPT versus stentriever thrombectomy in patients with emergent large vessel occlusions (ELVO) of the anterior intracranial circulation, the records of 134 patients who were treated between June 2012 and October 2015 were reviewed.RESULTSWithin this cohort, 117 patients were eligible for evaluation. ADAPT was used in 47 patients, 20 (42.5%) of whom required rescue stentriever thrombectomy, and primary stentriever thrombectomy was performed in 70 patients. Patients in the ADAPT group were slightly younger than those in the stentriever group (63.5 vs 69.4 years; p = 0.04); however, there were no differences in the other baseline clinical or radiographic factors. Procedural time (54.0 vs 77.1 minutes; p < 0.01) and time to a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b/3 recanalization (294.3 vs 346.7 minutes; p < 0.01) were significantly lower in patients undergoing ADAPT versus stentriever thrombectomy. The rates of TICI 2b/3 recanalization were similar between the ADAPT and stentriever groups (82.9% vs 71.4%; p = 0.19). There were no differences in the rates of symptomatic intracranial hemorrhage or procedural complications. The rates of good functional outcome (modified Rankin Scale Score 0–2) at 90 days were similar between the ADAPT and stentriever groups (48.9% vs 41.4%; p = 0.45), even when accounting for the subset of patients in the ADAPT group who required rescue stentriever thrombectomy.CONCLUSIONSThe present study demonstrates that ADAPT and primary stentriever thrombectomy for acute ischemic stroke due to ELVO are equivalent with respect to the rates of TICI 2b/3 recanalization and 90-day mRS scores. Given the reduced procedural time and time to TICI 2b/3 recanalization with similar functional outcomes, an initial attempt at recanalization with ADAPT may be warranted prior to stentriever thrombectomy.


2019 ◽  
Author(s):  
Massimo Gamba ◽  
Nicola Gilberti ◽  
Enrico Premi ◽  
Angelo Costa ◽  
Michele Frigerio ◽  
...  

Abstract Background and Purpose endovascular therapy (ET) is the standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). The role of adjunctive intravenous thrombolysis (IVT) in these patients is still unclear. The present study aims to test whether IVT plus ET (CoT, combined therapy) provides additional benefits over direct ET for anterior circulation AIS by LVO. Methods we performed a single center retrospective observational study of patients with AIS caused by anterior circulation LVO, referred to our center between January 2014 and January 2017 and treated with ET. The patients were divided in 2 groups based on the treatment they received: CoT and, if IVT contraindicated, direct ET. We compared functional recovery (modified Rankin at 3-months follow-up), recanalization rate (thrombolysis in cerebral infarction [TICI] score) and time, early follow-up infarct volume (EFIV) (for recanalized patients only) as well as safety profile, defined as symptomatic intracerebral hemorrhage (sICH) and 3-month mortality, between groups. Results 145 subjects were included in the study, 70 in direct ET group and 75 in CoT group. Patients who received CoT presented more frequently a functional independence at 3-months follow-up compared to patients who received direct ET (mRS score 0-1: 48.5% vs 18.6%; P<0.001. mRS score 0-2: 67.1% vs 37.3%; P<0.001), higher first-pass success rate (62.7% vs 38.6%, P<0.05), higher recanalization rate (84.3% vs 65.3%; P=0.009) and, in recanalized subjects, smaller EFIV (16.4ml vs 62.3ml; P=0.003). The safety profile was similar for the 2 groups. In multivariable regression analysis, low baseline NIHSS score (P<0.05), vessel recanalization (P=0.05) and CoT (P=0.03) were indipendent predictors of 3-month favorable outcome. Conclusions CoT appears more effective than ET alone for anterior circulation AIS with LVO, with similar safety profile.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Fausto E Ordonez ◽  
David Liebeskind ◽  
Mersedeh Bahr ◽  
Ashfaq Shuaib Shuaib ◽  
Natan Bornstein ◽  
...  

Background: Sphenopalatine ganglion (SPG) stimulation enhances collateral flow, stabilizes blood-brain barrier, and showed evidence of benefit in patients with confirmed cortical involvement (CCI) when started 8-24h after onset in the ImpACT-24B randomized trial. To characterize SPG stimulation benefit magnitude, we derived number needed to treat (NNT) values based on shifts over all levels of 3 month global disability. Methods: From the distribution of the 7-level modified Rankin Scale (mRS) at 3m in SPG- and sham-stimulation CCI patients, NNT to benefit (NNTB) and NNT to harm (NNTH) values were derived by automated (algorithmic min-max) and expert generation of joint outcome distribution tables. For dichotomized mRS outcomes, net NNT values were derived directly from absolute risk differences. Results: Among 520 patients with confirmed cortical infarction ineligible for thrombolysis, 244 were treated with SPG and 276 with sham stimulation. NNT values for dichotomized and shift mRS outcomes are shown in the Table. Of the 6 possible binary cutpoints on the mRS, 4 showed more favorable outcome with SPG stimulation. The dichotomized endpoint with the greatest group difference was ambulatory and capable of bodily self-care (mRS 0-3), 62.3% vs 51.1%, NNTB 8.9. Across all 6 individual possible dichotomizations of the mRS, the NNTB ranged from 8.9 to -166.7. For shifts by 1 or more levels across all 6 transitions of the mRS, the biologically most plausible NNTB was 5.7 (IQR 5.6-6.5), NNTH 34.5 (IQR 30.3-40.0), and net NNTB 6.8 (IQR 6.5-7.7), These values correlated closely with the automatically derived net NNTB of 5.9. Conclusions: The findings of this pivotal trial indicate that, out of every 1000 CCI patients treated with SPG stimulation, 146 patients will have a less disabled 3-month outcome, including 76 more who will be functionally independent. SPG stimulation can substantially improve the outcome of thrombolysis-ineligible acute ischemic stroke patients.


2018 ◽  
Vol 11 (7) ◽  
pp. 653-658 ◽  
Author(s):  
Annika Keulers ◽  
Omid Nikoubashman ◽  
Anastasios Mpotsaris ◽  
Scott D Wilson ◽  
Martin Wiesmann

BackgroundTo place a stent retriever for thrombectomy in acute ischemic stroke, the clot has to be passed first. A microwire is usually used for this maneuver. As an alternative, a wireless microcatheter can be used to pass the clot.ObjectiveTo analyze the feasibility and complication rates of passing the clot using either a microwire or a wireless microcatheter.MethodsA retrospective non-randomized analysis of 110 consecutive patients with acute ischemic stroke in the anterior circulation was performed, in whom video recordings of mechanical thrombectomies were available. In total, 203 attempts at mechanical recanalization were performed.ResultsSuccessful recanalization (TICI 2b–3) was achieved in 97.3% of patients. In 71.8% of attempts the clot was successfully passed using a wireless microcatheter only. When a microwire was used initially, clot passage was successful in 95.3% of attempts. Complication rates for angiographically detectable subarachnoid hemorrhage were 6.1% when a microwire was used to pass the clot compared with 0% when a wireless microcatheter was used (p<0.001). Complication rates for angiographically occult circumscribed subarachnoid contrast extravasation observed on post-interventional CT scans were 18.2% when a microwire was used to pass the clot and 4.5% when a wireless microcatheter was used (p<0.001).ConclusionsIn most cases of mechanical recanalization the clot can be passed with a wireless microcatheter instead of a microwire. In our study this method significantly reduced the risk for vessel perforation and subarachnoid hemorrhage. We therefore recommend the use of this technique whenever possible.


2017 ◽  
Vol 68 (2) ◽  
pp. 154-160 ◽  
Author(s):  
Elizabeth H.Y. Du ◽  
Jai J.S. Shankar

Stroke is the second leading cause of mortality and the third leading cause of disability-adjusted life-years worldwide. For each minute of an ischemic stroke, an estimated 1.9 million brain cells die. The year 2015 saw the unprecedented publication of 5 multicentre, randomized, controlled trials. These studies showed that patients with acute ischemic stroke caused by large-vessel thrombus occlusion of the proximal anterior circulation had significantly reduced disability at 90 days when treated with endovascular thrombectomy and usual stroke care compared to usual stroke care alone. As a result, endovascular thrombectomy is now the new North American and European standard of care for suitable patients with acute ischemic stroke caused by large-vessel proximal anterior circulation occlusion. We review key take-home messages in this paradigm shift for radiologists, including the importance of time and workflow efficiency, what currently constitutes appropriate preimaging patient selection and imaging criteria, the use of newer generation thrombectomy devices, safety outcomes, as well as further areas still in need of elucidation.


Stroke ◽  
2021 ◽  
Author(s):  
Imad Derraz ◽  
Mohamed Abdelrady ◽  
Nicolas Gaillard ◽  
Raed Ahmed ◽  
Federico Cagnazzo ◽  
...  

Background and Purpose: White matter hyperintensity (WMH), a marker of chronic cerebral small vessel disease, might impact the recruitment of leptomeningeal collaterals. We aimed to assess whether the WMH burden is associated with collateral circulation in patients treated by endovascular thrombectomy for anterior circulation acute ischemic stroke. Methods: Consecutive acute ischemic stroke due to anterior circulation large vessel occlusion and treated with endovascular thrombectomy from January 2015 to December 2017 were included. WMH volumes (periventricular, deep, and total) were assessed by a semiautomated volumetric analysis on fluid-attenuated inversion recovery–magnetic resonance imaging. Collateral status was graded on baseline catheter angiography using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system (good when ≥3). We investigated associations of WMH burden with collateral status. Results: A total of 302 patients were included (mean age, 69.1±19.4 years; women, 55.6%). Poor collaterals were observed in 49.3% of patients. Median total WMH volume was 3.76 cm 3 (interquartile range, 1.09–11.81 cm 3 ). The regression analyses showed no apparent relationship between WMH burden and the collateral status measured at baseline angiography (adjusted odds ratio, 0.987 [95% CI, 0.971–1.003]; P =0.12). Conclusions: WMH burden exhibits no overt association with collaterals in large vessel occlusive stroke.


2018 ◽  
Vol 10 (12) ◽  
pp. 1137-1142 ◽  
Author(s):  
Anna M M Boers ◽  
Ivo G H Jansen ◽  
Ludo F M Beenen ◽  
Thomas G Devlin ◽  
Luis San Roman ◽  
...  

BackgroundFollow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement.ObjectiveTo examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality.MethodsData of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated.ResultsOf 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14–120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15–131) vs 22 mL (IQR 8–71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively).ConclusionsIn patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.


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