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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 (R\(^2\) = 0.09696, p = 0.0373) and (4) greater infarct extent (R\(^2\) = 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.
Background
It is unknown whether technological advancement of stent-retriever devices influences typical observational indicators of safety or effectiveness.
Methods
Observational retrospective study of APERIO® (AP) vs. new generation APERIO® Hybrid (APH) (Acandis®, Pforzheim, Germany) stent-retriever device (01/2019–09/2020) for mechanical thrombectomy (MT) in large vessel occlusion (LVO) stroke. Primary effectiveness endpoint was successful recanalization eTICI (expanded Thrombolysis In Cerebral Ischemia) ≥ 2b67, primary safety endpoint was occurrence of hemorrhagic complications after MT. Secondary outcome measures were time from groin puncture to first pass and successful reperfusion, and the total number of passes needed to achieve the final recanalization result.
Results
A total of 298 patients with LVO stroke who were treated by MT matched the inclusion criteria: 148 patients (49.7%) treated with AP vs. 150 patients (50.3%) treated with new generation APH. Successful recanalization was not statistically different between both groups: 75.7% for AP vs. 79.3% for APH; p = 0.450. Postinterventional hemorrhagic complications and particularly subarachnoid hemorrhage as the entity possibly associated with stent-retriever device type was significantly less frequent in the group treated with the APH: 29.7% for AP and 16.0% for APH; p = 0.005; however, rates of symptomatic hemorrhage with clinical deterioration and in domo mortality were not statistically different. Neither the median number of stent-retriever passages needed to achieve final recanalization, time from groin puncture to first pass, time from groin puncture to final recanalization nor the number of cases in which successful recanalization could only be achieved by using a different stent-retriever as bail-out device differed between both groups.
Conclusion
In the specific example of the APERIO® stent-retriever device, we observed that further technological developments of the new generation device were not associated with disadvantages with respect to typical observational indicators of safety or effectiveness.
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.
Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion.
Objective
Blindness is a feared complication of giant cell arteritis (GCA). However, the spectrum of pathologic orbital imaging findings on magnetic resonance imaging (MRI) in GCA is not well understood. In this study, we assess inflammatory changes of intraorbital structures on black blood MRI (BB-MRI) in patients with GCA compared to age-matched controls.
Methods
In this multicenter case-control study, 106 subjects underwent BB-MRI. Fifty-six patients with clinically or histologically diagnosed GCA and 50 age-matched controls without clinical or laboratory evidence of vasculitis were included. All individuals were imaged on a 3-T MR scanner with a post-contrast compressed-sensing (CS) T1-weighted sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) BB-MRI sequence. Imaging results were correlated with available clinical symptoms.
Results
Eighteen of 56 GCA patients (32%) showed inflammatory changes of at least one of the intraorbital structures. The most common finding was enhancement of at least one of the optic nerve sheaths (N = 13, 72%). Vessel wall enhancement of the ophthalmic artery was unilateral in 8 and bilateral in 3 patients. Enhancement of the optic nerve was observed in one patient. There was no significant correlation between imaging features of inflammation and clinically reported orbital symptoms (p = 0.10). None of the age-matched control patients showed any inflammatory changes of intraorbital structures.
Conclusions
BB-MRI revealed inflammatory findings in the orbits in up to 32% of patients with GCA. Optic nerve sheath enhancement was the most common intraorbital inflammatory change on BB-MRI. MRI findings were independent of clinically reported orbital symptoms.
Key Points
• Up to 32% of GCA patients shows signs of inflammation of intraorbital structures on BB-MRI.
• Enhancement of the optic nerve sheath is the most common intraorbital finding in GCA patients on BB-MRI.
• Features of inflammation of intraorbital structures are independent of clinically reported symptoms.