How Clot Composition Influences Fibrinolysis in the Acute Phase of Stroke: A Proteomic Study of Cerebral Thrombi.

BACKGROUND: The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA). METHODS: In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FAout) by measuring D-dimer levels at the blood-thrombus interface and inside (FAin) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FAin, and FAout were determined by intravenous thrombolysis-adjusted linear regression. RESULTS: FAout (P<0.0001) and FAin (P=0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FAout was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FAout was increased with cardioembolic thrombi (72/104), which are rich in fibrin (P=0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit (P=0.0139), and hemoglobin level (P=0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FAout (P=0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FAout was significantly associated with reduced thrombus weight (P=0.0310), increased recanalization rate (P=0.0150), good clinical outcome (P=0.0480), and reduced mortality (P=0.0080). CONCLUSIONS: Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies.

Acute and Chronic Kidney Dysfunction and Prognosis following Thrombectomy for Ischemic Stroke.

INTRODUCTION: Patients with chronic kidney disease (CKD) have an increased risk of stroke, and CKD seems associated with worse outcome after a stroke. The main objective of our study RISOTTO was to evaluate the influence of CKD and acute kidney injury (AKI) on the clinical outcome and mortality of ischemic stroke patients after thrombolysis and/or thrombectomy. METHODS: This multicenter cohort study included patients in the acute phase of ischemic stroke due to large artery occlusion managed by thrombectomy. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS). RESULTS: 280 patients were included in the analysis. Fifty-nine patients (22.6%) had CKD. At 3 months, CKD was associated with similar functional prognosis (mRS 3-6: 50.0% vs. 41.7%, p = 0.262) but higher mortality (24.2% versus 9.5%, p = 0.004). In univariate analysis, patients with CKD had a higher burden of white matter hyperintensities (Fazekas score: 1.7 ± 0.8 vs. 1.0 ± 0.8, p = 0.002), lower initial infarct volume with equivalent severity, and lower recanalization success (86.4% vs. 97.0%, p = 0.008) compared to non-CKD patients. Forty-seven patients (20.0%) developed AKI. AKI was associated with poorer 3-month functional outcome (mRS 3-6: 63.8% vs. 49.0%, p = 0.002) and mortality (23.4% versus 7.7%, p = 0.002). In multivariate analysis, AKI appeared as an independent risk factor for poor functional outcome (mRS 3-6: adjOR 2.79 [1.11-7.02], p = 0.029) and mortality (adjOR 2.52 [1.03-6.18], p = 0.043) at 3 months, while CKD was not independently associated with 3-month mortality and poor neurological outcome. CONCLUSIONS: AKI is independently associated with poorer functional outcome and increased mortality at 3 months. CKD was not an independent risk factor for 3-month mortality or poor functional prognosis.

Virtual diluted cone beam CT for device apposition assessment during endovascular treatment of intracranial aneurysm: A technical note.

The increasing use of embolization devices with suboptimal radio-opacity to treat intracranial aneurysm underscores the need for advanced imaging techniques to characterize device-vessel interactions more accurately. Contrast-diluted cone-beam CT is commonly used in neurointervention but requires additional technical refinements to improve endovascular treatment assessment. In this technical note, we describe the virtual dilution cone beam CT (VDCBCT), a technique that synthetizes non-contrast and contrast-enhanced CBCT images to virtually dilute iodinated contrast agents, thereby facilitating a more accurate assessment of embolization device apposition. Through a set of intracranial aneurysms treated with different embolization devices, we describe the VDCBCT protocol and its usefulness for device apposition confidence. VDCBCT may enhance the global understanding of neurovascular embolization treatments by providing improved visualization of target vessels and low-radio-opacity embolization devices, obviating the need for contrast dilution.

Nonaneurysmal perimesencephalic subarachnoid hemorrhage on noncontrast head CT: An accuracy, inter-rater, and intra-rater reliability study.

BACKGROUND AND PURPOSE: To evaluate the reliability and accuracy of nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH) on Noncontrast Head CT (NCCT) between numerous raters. MATERIALS AND METHODS: 45 NCCT of adult patients with SAH who also had a catheter angiography (CA) were independently evaluated by 48 diverse raters; 45 raters performed a second assessment one month later. For each case, raters were asked: 1) whether they judged the bleeding pattern to be perimesencephalic; 2) whether there was blood anterior to brainstem; 3) complete filling of the anterior interhemispheric fissure (AIF); 4) extension to the lateral part of the sylvian fissure (LSF); 5) frank intraventricular hemorrhage; 6) whether in the hypothetical presence of a negative CT angiogram they would still recommend CA. An automatic NAPSAH diagnosis was also generated by combining responses to questions 2-5. Reliability was estimated using Gwet's AC1 (κG), and the relationship between the NCCT diagnosis of NAPSAH and the recommendation to perform CA using Cramer's V test. Multi-rater accuracy of NCCT in predicting negative CA was explored. RESULTS: Inter-rater reliability for the presence of NAPSAH was moderate (κG = 0.58; 95%CI: 0.47, 0.69), but improved to substantial when automatically generated (κG = 0.70; 95%CI: 0.59, 0.81). The most reliable criteria were the absence of AIF filling (κG = 0.79) and extension to LSF (κG = 0.79). Mean intra-rater reliability was substantial (κG = 0.65). NAPSAH weakly correlated with CA decision (V = 0.50). Mean sensitivity and specificity were 58% (95%CI: 44%, 71%) and 83 % (95%CI: 72 %, 94%), respectively. CONCLUSION: NAPSAH remains a diagnosis of exclusion. The NCCT diagnosis was moderately reliable and its impact on clinical decisions modest.

Traumatic axonal injury: Clinic, forensic and biomechanics perspectives.

Identification of Traumatic axonal injury (TAI) is critical in clinical practice, particularly in terms of long-term prognosis, but also for medico-legal issues, to verify whether the death or the after-effects were attributable to trauma. Multidisciplinary approaches are an undeniable asset when it comes to solving these problems. The aim of this work is therefore to list the different techniques needed to identify axonal lesions and to understand the lesion mechanisms involved in their formation. Imaging can be used to assess the consequences of trauma, to identify indirect signs of TAI, to explain the patient's initial symptoms and even to assess the patient's prognosis. Three-dimensional reconstructions of the skull can highlight fractures suggestive of trauma. Microscopic and immunohistochemical techniques are currently considered as the most reliable tools for the early identification of TAI following trauma. Finite element models use mechanical equations to predict biomechanical parameters, such as tissue stresses and strains in the brain, when subjected to external forces, such as violent impacts to the head. These parameters, which are difficult to measure experimentally, are then used to predict the risk of injury. The integration of imaging data with finite element models allows researchers to create realistic and personalized computational models by incorporating actual geometry and properties obtained from imaging techniques. The personalization of these models makes their forensic approach particularly interesting.

Endovascular therapy in patients with a large ischemic volume at presentation: An aggregate patient-level analysis.

INTRODUCTION: Recently, four randomized controlled trials (RCTs) have demonstrated the benefits of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) and a large ischemic core at baseline (LIC). The purpose of this study was to investigate the features influencing the clinical outcome and the benefits of mechanical thrombectomy in this subgroup. METHODS: We conducted a multicenter retrospective aggregate cohort study of patients with AIS-LVO and a LIC, assessed with quantitative core volume measures, treated with MT between 2012 and 2019. The data were queried through four registries, including patients with core volumes ≥50cc. Multivariable logistic regression models were employed to determine factors independently associated with clinical outcomes in patients with successful recanalization (modified-Thrombolysis-in-Cerebral-Infarction-score, mTICI=2b-3) and unsuccessful recanalization group (mTICI=0-2a). The primary endpoint was a favorable functional outcome at day-90, defined as a modified Rankin scale (mRS) of 0-3, accounting for the inherent severity of AIS with baseline LIC. Secondary outcomes included functional independence (mRS 0-2) at day-90, mortality, and symptomatic Intracranial Hemorrhage (sICH). RESULTS: A total of 460 patients were included (mean age 66±14.2 years; 39.6 % females). The mean baseline NIHSS was 20±5.2, and the core volume was 103.2±54.6 ml. Overall, 39.8 % (183/460) of patients achieved a favorable outcome at day-90 (mRS 0-3). Successful recanalization was significantly associated with a more frequent favorable outcome (aOR, 4.79; 95 %CI, 2.73-8.38; P<0.01) and functional independence (P<0.01). This benefit remained significant in older patients and in patients with cores above 100cc. At 90 days, 147/460 patients (32 %) were deceased, with successful recanalization significantly associated with less frequent mortality (OR, 0.34; 95 %CI, 0.22-0.53; P<0.01). The rate of sICH was 17.4 % and did not differ significantly between groups. CONCLUSIONS: In this large, pooled-cohort study of AIS-LVO patients with infarct cores over 50cc at baseline, we demonstrated that successful recanalization was associated with a better functional outcome, lower mortality, and similar rates of symptomatic intracranial hemorrhage for a wide spectrum of patients.

Safety and efficacy of stent retrievers plus contact aspiration in patients with acute ischaemic anterior circulation stroke and positive susceptibility vessel sign in France (VECTOR): a randomised, single-blind trial.

BACKGROUND: Positive susceptibility vessel sign (SVS) in patients with acute ischaemic stroke has been associated with friable red blood cell-rich clots and more effective recanalisation using stent retrievers versus contact aspiration. We compared the safety and efficacy of stent retrievers plus contact aspiration (combined technique) versus contact aspiration alone as the first-line thrombectomy technique in patients with acute ischaemic anterior circulation stroke and SVS-positive occlusions. METHODS: Adaptive Endovascular Strategy to the Clot MRI in Large Intracranial Vessel Occlusion (VECTOR) was a prospective, randomised, open-label study with blinded evaluation. Patients with SVS-positive anterior circulation occlusions on pretreatment MRI and arterial puncture within 24 h of symptom onset were enrolled from 22 centres in France. A centralised web-based method was used by interventional neuroradiologists for dynamic randomisation by minimisation. Patients were randomly assigned 1:1 to the combined technique or contact aspiration alone. The primary outcome was expanded Thrombolysis in Cerebral Infarction (eTICI) grade 2c or 3 reperfusion after three or fewer passes on post-treatment angiogram, adjudicated by a blinded independent central imaging core laboratory. The intention-to-treat population was used to assess the primary and secondary outcomes. This trial is registered with ClinicalTrials.gov (NCT04139486) and is complete. FINDINGS: Between Nov 26, 2019, and Feb 14, 2022, 526 patients were enrolled, of whom 521 constituted the intention-to-treat population (combined technique, n=263; contact aspiration alone, n=258). The median age of participants was 74·9 years (IQR 64·4-83·3); 284 (55%) were female and 237 (45%) male. The primary outcome did not differ significantly between groups (152 [58%] of 263 patients for the combined technique vs 135 [52%] of 258 for contact aspiration; odds ratio [OR] 1·27; 95% CI 0·88-1·83; p=0·19). Procedure-related adverse events occurred in 32 (12%) of 263 patients in the combined technique group and 27 (11%) of 257 in the contact aspiration group (OR 1·14; 0·65-2·00; p=0·65). The most common adverse event was intracerebral haemorrhage (146 [56%] of 259 patients for the combined technique vs 123 [49%] of 251 for contact aspiration; OR 1·32; 0·91-1·90; p=0·13). All-cause mortality at 3 months occurred in 57 (23%) of 251 patients in the combined technique group and 48 (19%) of 247 in the contact aspiration group (OR 1·19; 0·76-1·86; p=0·45), none of which was treatment-related. INTERPRETATION: The results of the VECTOR trial do not show superiority of the combined stent retriever plus contact aspiration technique over contact aspiration alone in patients with SVS-positive occlusion with respect to achieving eTICI 2c-3 within three passes. These findings support the use of either the combined technique or contact aspiration alone as the initial thrombectomy strategy in patients with acute anterior circulation stroke with SVS on pretreatment MRI. FUNDING: Cerenovus.