scholarly journals Immune Cells Invade the Collateral Circulation during Human Stroke: Prospective Replication and Extension

2021 ◽  
Vol 22 (17) ◽  
pp. 9161
Author(s):  
Marc Strinitz ◽  
Mirko Pham ◽  
Alexander G. März ◽  
Jörn Feick ◽  
Franziska Weidner ◽  
...  

It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We prospectively studied a large independent cohort of n = 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468, p = 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438, p = 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R2 = 0.09696, p = 0.0373) and (4) greater infarct extent (R2 = 0.08382, p = 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment.

Author(s):  
Alexander M. Kollikowski ◽  
Mirko Pham ◽  
Alexander G. März ◽  
Lena Papp ◽  
Bernhard Nieswandt ◽  
...  

AbstractExperimental evidence has emerged that local platelet activation contributes to inflammation and infarct formation in acute ischemic stroke (AIS) which awaits confirmation in human studies. We conducted a prospective observational study on 258 consecutive patients undergoing mechanical thrombectomy (MT) due to large-vessel-occlusion stroke of the anterior circulation (08/2018–05/2020). Intraprocedural microcatheter aspiration of 1 ml of local (occlusion condition) and systemic arterial blood samples (self-control) was performed according to a prespecified protocol. The samples were analyzed for differential leukocyte counts, platelet counts, and plasma levels of the platelet-derived neutrophil-activating chemokine C-X-C-motif ligand (CXCL) 4 (PF-4), the neutrophil attractant CXCL7 (NAP-2), and myeloperoxidase (MPO). The clinical-biological relevance of these variables was corroborated by specific associations with molecular-cellular, structural-radiological, hemodynamic, and clinical-functional parameters. Seventy consecutive patients fulfilling all predefined criteria entered analysis. Mean local CXCL4 (+ 39%: 571 vs 410 ng/ml, P = .0095) and CXCL7 (+ 9%: 693 vs 636 ng/ml, P = .013) concentrations were higher compared with self-controls. Local platelet counts were lower (− 10%: 347,582 vs 383,284/µl, P = .0052), whereas neutrophil counts were elevated (+ 10%: 6022 vs 5485/µl, P = 0.0027). Correlation analyses revealed associations between local platelet and neutrophil counts (r = 0.27, P = .034), and between CXCL7 and MPO (r = 0.24, P = .048). Local CXCL4 was associated with the angiographic degree of reperfusion following recanalization (r =  − 0.2523, P = .0479). Functional outcome at discharge correlated with local MPO concentrations (r = 0.3832, P = .0014) and platelet counts (r = 0.288, P = .0181). This study provides human evidence of cerebral platelet activation and platelet-neutrophil interactions during AIS and points to the relevance of per-ischemic thrombo-inflammatory mechanisms to impaired reperfusion and worse functional outcome following recanalization.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Destiny Hooper ◽  
Tariq Nisar ◽  
Meryim Poursheykhi ◽  
Andy Lin ◽  
C. David McCane ◽  
...  

Objective: Recent studies have shown the benefit of revascularization in select patients with extended window large vessel occlusion (EWLVO). We sought to assess the effect of cerebral small vessel disease (CSVD) burden on eligibility for intervention with mechanical thrombectomy (MT) and functional outcomes in patients with EWLVO. Methods: We conducted a retrospective single-center study of 135 patients with anterior circulation LVO who presented in the extended time window, 6 to 24 hours from LKW, between August 2018 and March 2020. All patients underwent perfusion imaging at initial presentation and those with target ischemic core to penumbra mismatch profiles, as defined by DAWN/DEFUSE3 criteria, were treated with MT. Included patients were evaluated for CSVD burden using T2-FLAIR MRI. The Fazekas scale (0-3) was used to quantify the amount of white matter T2 hyperintense lesions in both the periventricular (PVWM) and deep white matter (DWM). Patients’ functional outcomes were assessed at 90 days using the mRS. Multivariate ordinal logistic regression models were used and adjusted for age, gender, thrombus location and LKW to perfusion imaging time. Patient information was collected from the Houston Methodist Hospital Outcomes Based Prospective Endpoints in Stroke (HOPES) registry. Results: Of the 135 patients, 111 met imaging inclusion criteria for revascularization with MT for EWLVO. MT was deferred in 44 of these patients due to other clinical exclusions or patient refusal. Patients ineligible for MT were approximately 13 times more likely to have a higher PVWM Fazekas grade (OR =13.53, 95% CI. [2.94 - 62.39], p=0.001) and 17 times more likely to have a higher DWM Fazekas grade (OR =17.54, 95% CI. [4.20 - 73.17], p<0.001), when compared to patients who were eligible for MT. Patients who did not meet criteria for MT were nearly 7 times more likely to have poor functional outcomes at 90 days (OR =6.85, 95% CI. [2.09 - 22.44], p=0.001). Conclusion: Based on our analytical cohort of EWLVO patients, those with severe CSVD burden were more likely to be excluded from MT and had worse functional outcomes. Poor cerebrovascular reserve and diminished collateral flow leading to rapid infarct progression in patients with greater CSVD burden may be a potential explanation.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Tetsuya Hashimoto ◽  
Takenobu Kunieda ◽  
Tristan Honda ◽  
Fabien Scalzo ◽  
Latisha K Sharma ◽  
...  

Background and Purpose: Acute leptomeningeal collateral flow is vital to maintain blood perfusion to penumbral tissue in acute ischemic stroke due to large vessel occlusion (LVO). However, the degree of this collateral flow differs among patients. Patient premorbid factors as well as factors caused by the mechanisms of stroke are expected to be associated with this collateral flow. We aimed to investigate the clinical determinants of acute leptomeningeal collateral flow in embolic LVO. Methods: Among consecutive stroke patients caused by acute embolic anterior circulation LVO, we retrospectively reviewed 108 patients who underwent evaluation of acute leptomeningeal collateral status (CS) on pretreatment CTA admitted from January 2015 to December 2019. Both premorbid information including cerebrovascular risk factors and leukoaraiosis evaluated by the total white matter (WM) Fazekas score on MRI, which was calculated as periventricular plus deep WM scores, and stroke related information including stroke subtypes, severity, time course, and occlusive thrombus characteristics were collected. Among thrombus characteristics, thrombus length was measured by tracing the filling defect of contrast on CTA. The clinical determinants of good leptomeningeal CS (> 50% collateral filling of the occluded territory) were analyzed. Results: CS was good in 67 patients (62%). On multivariate logistic regression analysis, cardioembolic stroke subtype was negatively related (OR, 0.170; 95% CI, 0.022-0.868), and mild leukoaraiosis (total WM Fazekas scores of 0-2) was positively related (OR, 9.57; 95% CI, 2.49-47.75) to good CS. On subgroup analysis limited to 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.913 per mm increase; 95% CI, 0.819-0.999) as well as mild leukoaraiosis (OR, 5.79; 95% CI, 1.40-29.61) were independently related to good CS. Conclusions: Premorbid leukoaraiosis and cardioembolic etiology are determinants of acute leptomeningeal collateral flow in embolic LVO. In addition, thrombus length is also a determinant of collateral flow in cardioembolic LVO. These findings indicate that a combination of chronic cerebrovascular damage and acute embolic mechanisms could determine the degree of leptomeningeal collateral flow.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Kambiz Nael ◽  
Jonathan Larson ◽  
Yu Sakai ◽  
Jared Goldstein ◽  
Jacob Deutsch ◽  
...  

Purpose: Perfusion collateral index (PCI) has been recently defined as a promising measure of collateral flow. We aim to evaluate the collateral status via CT-based PCI in association with outcome measures such as final infraction volume, recanalization status and functional outcome in patients presenting with acute ischemic stroke (AIS) and in a comparative analysis against CTA and DSA collateral scores. Methods: AIS patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion and underwent endovascular treatment were included. CTA collateral scores were calculated using modified Tan score and DSA collateral scores were evaluated by ASITN grading. In addition, previously described PCI defined as the volume of moderately hypoperfused tissue (ATD 2-6sec ) multiplied by its corresponding rCBV was calculated in each patient. The association of CTA and DSA collateral scores and PCI were assessed against 3 measured outcomes: 1) Final infarction volume obtained from follow up MRI; 2) Final recanalization status defined by TICI scores; 3) Functional outcome measured by 90-day mRS. Results: A total of 53 patients met inclusion criteria (27F; mean/SD age: 70.1 ± 13 years; median NIHSS: 14). Final infarction volume (mean/SD: 30/40 mL), excellent recanalization defined by TICI >2C was achieved in 36 (68%) patients, and 23 patients (43%) had good functional outcome (mRS <2). Having good collaterals on all 3 modalities (CTA, DSA, CTP-PCI) were associated with significantly (p<0.05) smaller infarction volume. However only good collaterals determined by CTP-PCI was predictive of achieving excellent recanalization (p=0.001) or good functional outcome (p=0.01) ( Figure 1 ). Conclusion: Collateral status assessed via CT-PCI outperforms CTA and DSA collateral scores in prediction of excellent recanalization and good functional outcome and may be a promising imaging biomarker of collateral status in patients with AIS.


2020 ◽  
pp. 0271678X2095492
Author(s):  
Adrien ter Schiphorst ◽  
Sylvain Charron ◽  
Wagih Ben Hassen ◽  
Corentin Provost ◽  
Olivier Naggara ◽  
...  

Despite early thrombectomy, a sizeable fraction of acute stroke patients with large vessel occlusion have poor outcome. The no-reflow phenomenon, i.e. impaired microvascular reperfusion despite complete recanalization, may contribute to such “futile recanalizations”. Although well reported in animal models, no-reflow is still poorly characterized in man. From a large prospective thrombectomy database, we included all patients with intracranial proximal occlusion, complete recanalization (modified thrombolysis in cerebral infarction score 2c–3), and availability of both baseline and 24 h follow-up MRI including arterial spin labeling perfusion mapping. No-reflow was operationally defined as i) hypoperfusion ≥40% relative to contralateral homologous region, assessed with both visual (two independent investigators) and automatic image analysis, and ii) infarction on follow-up MRI. Thirty-three patients were eligible (median age: 70 years, NIHSS: 18, and stroke onset-to-recanalization delay: 208 min). The operational criteria were met in one patient only, consistently with the visual and automatic analyses. This patient recanalized 160 min after stroke onset and had excellent functional outcome. In our cohort of patients with complete and stable recanalization following thrombectomy for intracranial proximal occlusion, severe ipsilateral hypoperfusion on follow-up imaging associated with newly developed infarction was a rare occurrence. Thus, no-reflow may be infrequent in human stroke and may not substantially contribute to futile recanalizations.


Author(s):  
R Kiwan ◽  
S Lownie

Background: The circle of Willis (CoW) and cervical carotid arteries are important sources of collateral flow during acute large vessel occlusion (LVO) in the anterior circulation. We examined the anatomical components of the circle and the cervical carotid arteries to determine relationship to acute stroke severity. Methods: Consecutive patients with acute LVO who underwent EVT were assessed. Measurements were made of the luminal diameters of 16 anatomical vascular components. Admission NIHSS, ASPECTS and mCTA collateral scores were statistically analyzed for any relationship to vascular measurements. Results: 100 patients were studied. No relationship was found between the collateral Willisian pathways and measures of stroke severity. However, the ophthalmic arteries exhibited a relationship to stroke severity. In adjusted analysis, 1-mm increases in the ipsilateral and contralateral ophthalmic artery diameter were independently associated with a 4.80-point decrease and a 6.31-point increase in the NIHSS scale, respectively. Similarly, a 1.53-point increase and a 2.62-point decrease in the ASPECTS. In the neck a majority showed 0-55% stenosis, with no stenosis between 55% and 95%, and 14% at 95% to 100%. Conclusions: Stroke severity and collateral during LVO is unrelated to Willisian collateral. Ophthalmic artery calibers are related. Acute progression of 55-95% stenoses to complete occlusion occurs in LVO stroke


2020 ◽  
Vol 12 (10) ◽  
pp. 942-945 ◽  
Author(s):  
Ian Mark ◽  
Seyed Mohammad Seyedsaadat ◽  
John C Benson ◽  
David F Kallmes ◽  
Alejandro A Rabinstein ◽  
...  

BackgroundLeukoaraiosis and collateral blood flow are processes that involve small vessels, the former related to flow within the deep perforating arterioles and the latter involving the small, cortical pial-pial connections, both of which are independently used to predict cerebrovascular events and treatment outcomes. The aim of this study was to investigate their relationship to each other.MethodsWe retrospectively reviewed patients who underwent mechanical thrombectomy for stroke with pre-procedural CT imaging within 24 hours of the onset of symptoms. Leukoaraiosis was graded by the total Fazekas score on non-contrast CT, periventricular white matter (PVWM) and deep white matter (DWM) scores, both ranging from 0 to 3. Collateral cerebral blood flow was measured by the American Society of Interventional and Therapeutic Radiology/Society of Interventional Radiology (ASITN/SIR) collateral scale.Results178 patients were included with a mean age of 67.6±14.8 years. We found an inverse relationship between total Fazekas score and collateral flow (p<0.0001). Among patients with good collaterals, 75.1% had total Fazekas scores of 0–2, compared with 36.6% of patients with moderate collaterals and 32.7% of patients with poor collaterals with total Fazekas scores of 0–2. Mean Fazekas scores were 1.6±1.5, 3.1±1.5 and 3.4±1.6 for good, moderate and poor collaterals, respectively (p<0.0001). On multivariate analysis, total Fazekas score was the only variable independently associated with collateral status (p<0.0001).ConclusionsIncreasing severity of leukoaraiosis is associated with poor collateral grade among ischemic stroke patients with anterior circulation large vessel occlusion. These findings suggest that leukoaraiosis may be a marker for global cerebrovascular dysfunction.


2021 ◽  
pp. 174749302110192
Author(s):  
Mahmoud H Mohammaden ◽  
Diogo C. Haussen ◽  
Leonardo Pisani ◽  
Alhamza Al-Bayati ◽  
Aaron Anderson ◽  
...  

Background Three randomized clinical trials have reported similar safety and efficacy for contact aspiration (CA) and Stent-retriever (SR) thrombectomy. Aim We aimed to determine whether the Combined Technique (SR+CA) was superior to SR alone as first-line thrombectomy strategy in a patient cohort where balloon-guide catheter was universally used. Methods A prospectively maintained mechanical thrombectomy database from January 2018-December 2019 was reviewed. Patients were included if they had anterior circulation proximal occlusion ischemic stroke (intracranial ICA or MCA-M1/M2 segments) and underwent SR alone thrombectomy or SR+CA as first-line therapy. The primary outcome was the first-pass effect (FPE) (mTICI2c-3). Secondary outcomes included modified FPE (mTICI2b-3), successful reperfusion (mTICI2b-3) prior to and after any rescue strategy, and 90-day functional independence (mRS ≤2). Safety outcomes included rate of parenchymal hematoma (PH) type-2 and 90-day mortality. Sensitivity analyses were performed after dividing the overall cohort according to first-line modality into two matched groups. Results A total of 420 patients were included in the analysis (mean age 64.4 years; median baseline NIHSS 16[11-21]). As compared to first-line SR alone, first-line SR+CA resulted in similar rates of FPE (53% vs. 51%,aOR 1.122, 95%CI[0.745-1.691],p=0.58), mFPE (63% vs. 60.4%,aOR1.250, 95%CI[0.782-2.00],p=0.35), final successful reperfusion (97.6% vs. 98%,p=0.75) and higher chances of successful reperfusion prior to any rescue strategy (81.8% vs. 72.5%,aOR 2.033, 95%CI[1.209-3.419],p=0.007). Functional outcome and safety measures were comparable between both groups. Likewise, the matched analysis (148 patient-pairs) demonstrated comparable results for all clinical and angiographic outcomes except for significantly higher rates of successful reperfusion prior to any rescue strategies with the first-line SR+CA treatment (81.8% vs. 73.6%,aOR 1.881, 95%CI[1.039-3.405],p=0.037). Conclusions Our findings reinforce the findings of ASTER-2 trial in that the first-line thrombectomy with a Combined Technique did not result in increased rates of first-pass reperfusion or better clinical outcomes. However, addition of contact aspiration after initial SR failure might be beneficial in achieving earlier reperfusion.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhen Jing ◽  
Hao Li ◽  
Shengming Huang ◽  
Min Guan ◽  
Yongxin Li ◽  
...  

AbstractEndovascular treatment (EVT) has been accepted as the standard of care for patients with acute ischemic stroke. The aim of the present study was to compare clinical outcomes of patients who received EVT within and beyond 6 h from symptom onset to groin puncture without perfusion software in Guangdong district, China. Between March 2017 and May 2018, acute ischemic stroke patients who received EVT from 6 comprehensive stroke centers, were enrolled into the registry study. In this subgroup study, we included all patients who had acute proximal large vessel occlusion in the anterior circulation. The demographic, clinical and neuroimaging data were collected from each center. A total of 192 patients were included in this subgroup study. They were divided into two groups: group A (n = 125), within 6 h; group B (n = 67), 6–24 h from symptom onset to groin puncture. There were no substantial differences between these two groups in terms of 90 days favorable outcome (modified Rankin scale [mRS] ≤ 2, P = 0.051) and mortality (P = 0.083), and the risk of symptomatic intracranial hemorrhage at 24 h (P = 0.425). The NIHSS (median 16, IQR12-20, group A; median 12, IQR8-18, group B; P = 0.009) and ASPECTS (median 10, IQR8-10, group A; median 9, IQR8-10, group B; P = 0.034) at baseline were higher in group A. The anesthesia method (general anesthesia, 21.3%, group A vs. 1.5% group B, P = 0.001) were also statistically different between the two groups. The NIHSS and ASPECTS were higher, and general anesthesia was also more widely used in group A. Clinical outcomes were not significantly different within 6 h versus 6–24 h from symptom onset to groin puncture in this real world study.


Author(s):  
Juha-Pekka Pienimäki ◽  
Jyrki Ollikainen ◽  
Niko Sillanpää ◽  
Sara Protto

Abstract Purpose Mechanical thrombectomy (MT) is the first-line treatment in acute stroke patients presenting with large vessel occlusion (LVO). The efficacy of intravenous thrombolysis (IVT) prior to MT is being contested. The objective of this study was to evaluate the efficacy of MT without IVT in patients with no contraindications to IVT presenting directly to a tertiary stroke center with acute anterior circulation LVO. Materials and Methods We collected the data of 106 acute stroke patients who underwent MT in a single high-volume stroke center. Patients with anterior circulation LVO eligible for IVT and directly admitted to our institution who subsequently underwent MT were included. We recorded baseline clinical, laboratory, procedural, and imaging variables and technical, imaging, and clinical outcomes. The effect of intravenous thrombolysis on 3-month clinical outcome (mRS) was analyzed with univariate tests and binary and ordinal logistic regression analysis. Results Fifty-eight out of the 106 patients received IVT + MT. These patients had 2.6-fold higher odds of poorer clinical outcome in mRS shift analysis (p = 0.01) compared to MT-only patients who had excellent 3-month clinical outcome (mRS 0–1) three times more often (p = 0.009). There were no significant differences between the groups in process times, mTICI, or number of hemorrhagic complications. A trend of less distal embolization and higher number of device passes was observed among the MT-only patients. Conclusions MT without prior IVT was associated with an improved overall three-month clinical outcome in acute anterior circulation LVO patients.


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