Objective: Bridging the gap between experimental stroke and patients by ischemic blood probing during the hyperacute stage of vascular occlusion is crucial to assess the role of inflammation in human stroke and for the development of adjunct treatments beyond recanalization.Methods: We prospectively observed 151 consecutive ischemic stroke patients with embolic large vessel occlusion of the anterior circulation who underwent mechanical thrombectomy. In all these patients, we attempted microcatheter aspiration of 3 different arterial blood samples: (1) within the core of the occluded vascular compartment and controlled by (2) carotid and (3) femoral samples obtained under physiological flow conditions. Subsequent laboratory analyses comprised leukocyte counting and differentiation, platelet counting, and the quantification of 13 proinflammatory human chemokines/cytokines.Results: Forty patients meeting all clinical, imaging, interventional, and laboratory inclusion criteria could be analyzed, showing that the total number of leukocytes significantly increased under the occlusion condition. This increase was predominantly driven by neutrophils. Significant increases were also apparent for lymphocytes and monocytes, accompanied by locally elevated plasma levels of the T‐cell chemoattractant CXCL‐11. Finally, we found evidence that short‐term clinical outcome (National Institute of Health Stroke Scale at 72 hours) was negatively associated with neutrophil accumulation.Interpretation: We provide the first direct human evidence that neutrophils, lymphocytes, and monocytes, accompanied by specific chemokine upregulation, accumulate in the ischemic vasculature during hyperacute stroke and may affect outcome. These findings strongly support experimental evidence that immune cells contribute to acute ischemic brain damage and indicate that ischemic inflammation initiates already during vascular occlusion. Ann Neurol 2020;87:466–479

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke in the anterior circulation are at risk for either primary or, following mechanical thrombectomy, secondary occlusion of the anterior cerebral artery. Because previous studies had only a limited informative value, we report our data concerning the frequency and location of distal anterior cerebral artery occlusions, recanalization rates, periprocedural complications, and clinical outcome. MATERIALS AND METHODS: We performed a retrospective analysis of prospectively collected data of patients with acute ischemic stroke undergoing mechanical thrombectomy in the anterior circulation between June 2010 and April 2015. RESULTS: Of 368 patients included in this analysis, we identified 30 (8.1%) with either primary (n = 17, 4.6%) or secondary (n = 13, 3.5%) embolic occlusion of the distal anterior cerebral artery. The recanalization rate after placement of a stent retriever was 88%. Periprocedural complications were rare and included vasospasms (n = 3, 10%) and dissection (n = 1, 3.3%). However, 16 (53.5%) patients sustained an (at least partial) infarction of the anterior cerebral artery territory. Ninety days after the ictus, clinical outcome according to the modified Rankin Scale score was the following: 0–2, n = 11 (36.6%); 3–4, n = 9 (30%); 5–6, n = 10 (33.3%). CONCLUSIONS: Occlusions of the distal anterior cerebral artery affect approximately 8% of patients with acute ischemic stroke in the anterior circulation receiving mechanical thrombectomy. Despite a high recanalization rate and a low complication rate, subsequent (partial) infarction in the anterior cerebral artery territory occurs in approximately half of patients. Fortunately, clinical outcome appears not to be predominately unfavorable.

Experimental 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.

BACKGROUND AND PURPOSE: In the treatment of acute thromboembolic stroke, the effectiveness and success of thrombus removal when using stent retrievers is variable. In this study, we analyzed the correlation of thrombectomy maneuver count with a good clinical outcome and recanalization success. MATERIALS AND METHODS: One hundred and four patients with acute occlusion of the middle cerebral artery or the terminal internal carotid artery who were treated with thrombectomy were included in this retrospective study. A good clinical outcome was defined as a 90-day mRS of ≤2, and successful recanalization was defined as TICI 2b–3. RESULTS: The maneuver count ranged between 1–10, with a median of 2. Multivariate logistic regression analyses identified an increasing number of thrombectomy maneuvers as an independent predictor of poor outcome (adjusted OR, 0.59; 95% CI, 0.38–0.87; P = .011) and unsuccessful recanalization (adjusted OR, 0.48; 95% CI, 0.32–0.66; P < .001). A good outcome was significantly more likely if finished within 2 maneuvers compared with 3 or 4 maneuvers, or even more than 4 maneuvers (P < .001). CONCLUSIONS: An increasing maneuver count correlates strongly with a decreasing probability of both good outcome and recanalization. The probability of successful recanalization decreases below 50% if not achieved within 5 thrombectomy maneuvers. Patients who are recanalized within 2 maneuvers have the best chance of achieving a good clinical outcome.

Ischemic stroke caused by thromboembolic occlusion of large cerebral arteries, such as the internal carotid (ICA) and/or the middle cerebral artery (MCA), is treated by mechanical thrombectomy (MT). MT allows salvage of the vessel-occluding thrombemboli, which most frequently originate from the left atrium or the left ventricle of the heart or from sites of plaque rupture within large arteries above the heart. Clot composition may influence the efficacy of (intravenous) thrombolysis and MT, respectively. We analyzed 37 human thrombemboli obtained from acute ischemic stroke patients during MT with special emphasis on histological staining of neutrophils and neutrophil extracellular traps (NETs). We found neutrophils as the main cellular component of cerebral thrombemboli but encountered considerable morphological heterogeneity. Neutrophils accumulated in the border region of fibrin-rich structures indicating possible interaction of neutrophils with distinct structural thrombembolus components. Web-like NETs were found in 35 of 37 thrombemboli in varying amounts. NETs were almost exclusively found within fibrin-rich areas. Importantly, stroke etiology, age and present oral anticoagulation was associated with morphological patterns and the amount of neutrophils. Correlation of histological data and imaging data revealed that relative Hounsfield units of cerebral thrombemboli positively correlated with the amount of red blood cells. In summary, our results demonstrate that neutrophils and NETs are substantial constituents of cerebral thrombemboli and contribute to their structural complexity.

BACKGROUND AND PURPOSE: Mechanical thrombectomy, in addition to intravenous thrombolysis, has become standard in acute ischemic stroke treatment in patients with large-vessel occlusion in the anterior circulation. However, previous randomized controlled stroke trials were not focused on patients with mild-to-moderate symptoms. Thus, there are limited data for patient selection, prediction of clinical outcome, and occurrence of complications in this patient population. The purpose of this analysis was to assess clinical and interventional data in patients treated with mechanical thrombectomy in case of ischemic stroke with mild-to-moderate symptoms. MATERIALS AND METHODS: We performed a retrospective analysis of a prospectively collected stroke data base. Inclusion criteria were anterior circulation ischemic stroke treated with mechanical thrombectomy at our institution between September 2010 and October 2015 with an NIHSS score of ≤8. RESULTS: Of 484 patients, we identified 33 (6.8%) with the following characteristics: median NIHSS = 5 (interquartile range, 4–7), median onset-to-groin puncture time = 320 minutes (interquartile range, 237–528 minutes). Recanalization (TICI = 2b–3) was achieved in 26 (78.7%) patients. Two cases of symptomatic intracranial hemorrhage were observed. Favorable (mRS 0–2) and moderate (mRS 0–3) clinical outcome at 90 days was achieved in 21 (63.6%) and 30 (90.9%) patients, respectively. CONCLUSIONS: The clinical outcome of patients undergoing mechanical thrombectomy for acute ischemic stroke with mild stroke due to large-vessel occlusion appears to be predominately favorable, even in a prolonged time window. However, although infrequent, angiographic complications could impair clinical outcome. Future randomized controlled trials should assess the benefit compared with the best medical treatment.