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Abstract Objective The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke‐unit (SU)—access, acute reperfusion therapy—use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. Methods AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris‐area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age‐, initial NIHSS‐ and sex‐matched HIV‐uninfected controls (HUCs). Outcome was the 90‐day modified Rankin Scale score. Results Among 126 PLHIVs with confirmed first‐ever AIS, ~80% were admitted outside the thrombolysis‐administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small‐vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%–30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well‐tolerated. Interpretation The high uncontrolled HIV‐infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

Introduction Lesion volume measurement provides an objective and quantitative assessment of stroke severity and it is often used as a surrogate endpoint of clinical outcome in therapeutic trials. ACTIMIS (NCT03803007) was a randomized phase 1b/2a clinical trial evaluating glenzocimab, a monoclonal antibody fragment targeting platelet receptor glycoprotein VI, versus placebo in patients with acute ischemic stroke treated by thrombolysis alone or associated with mechanical thrombectomy (MT), both subgroups being well balanced. Primary analysis demonstrated a significant reduction in intracranial hemorrhage occurrence stroke‐related mortality and a trend towards reduction in severe disability. In this sub‐analysis, Artificial Intelligence (AI) imaging biomarkers were used to assess efficacy of glenzocimab in the subgroup undergoing MT in the pooled phase 1b (dose escalation) and phase 2a (dose confirmation) studies. Methods In the phase 1b study, patients were randomized to an escalating dose of glenzocimab or placebo (4:1, n=12 per group, 125mg, 250mg, 500mg, 1000mg). In the phase 2 dose confirmation study, patients were randomized (1:1) with 1000mg glenzocimab or placebo. CT scan or MRI was acquired at baseline with CT at 24 hours and MRI at 7 days (CT if MRI not available) for safety and efficacy analysis, respectively. Baseline and follow up imaging were processed using Brainomix software (Oxford, UK). AI output was reviewed for accuracy by an expert clinician (DC) blinded to treatment allocation. Results Of 166 patients in the trial, 81 patients underwent MT and had follow up non‐contrast CT imaging available at 24 hours (48 glenzocimab, 33 placebo) and 72 had Day‐7 imaging (47 glenzocimab, 25 placebo). Day‐7 imaging was available for 8 fewer placebo patients and 1 glenzocimab patient than at 24 hours. All except 2 patients (1 placebo, 1 glenzocimab) with missing data at Day‐7 died during the study. Multivariate regression modelling showed a significant interaction between patients undergoing MT and receiving glenzocimab. Glenzocimab had a greater effect on reducing the risk of haemorrhagic transformation in the MT subgroup (exploratory p=0.001). Presenting acute infarct volume was similar between glenzocimab and placebo arms (mean [SD]; 16.27mL [30.2] vs. 19.62mL [28.98], non‐significant). There was a significantly smaller volume of haemorrhagic transformation in the glenzocimab group at 24 hours compared to placebo (1.83mL [6.59] vs 33.46mL [75.07], exploratory p

Background Both aspiration and stent retriever thrombectomy are safe and effective in patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation. Little is known on the outcomes of these techniques in patients with basilar artery occlusion. This study aimed to compare clinical, technical, and safety outcomes of aspiration and stent retriever thrombectomy as first‐line treatment for basilar artery occlusion in the BASICS (Basilar artery International Cooperation Study) trial. Methods For this post hoc analysis of the BASICS trial, all patients with a basilar artery occlusion who received endovascular treatment with either direct aspiration or stent retriever thrombectomy as first‐line approach were included. When both techniques were registered as first choice, patients were considered to have been treated with stent retriever. The primary outcome was favorable functional outcome, defined as a modified Rankin scale score of 0–3 at 90 days follow‐up, and analyzed using binary logistic regression analysis. Secondary outcomes included the modified Rankin scale score at 90 days (ranging from 0 to 6), procedure duration, mortality at 90 days, and symptomatic intracranial hemorrhage. Secondary outcomes were analyzed using binary, linear, or ordinal regression analyses. All analyses were adjusted for predefined variables. Results Among 158 BASICS patients treated with endovascular treatment,127 were treated with either stent retriever (N=67, 53%), or aspiration (N=60, 47%) as the first‐line treatment modality. We observed no significant difference in favorable functional outcome between patients treated with aspiration and stent retriever thrombectomy as first modality (adjusted odds ratio, 1.80; [95% CI, 0.68–4.76]). Also modified Rankin scale score at 90 days (adjusted common odds ratio, 0.62; [95% CI, 0.30–1.27]) and incidence of symptomatic intracranial hemorrhage (adjusted odds ratio, 0.61; [95% CI, 0.08–4.76]) showed no significant differences between both techniques. Procedure time was shorter with a median of 32 versus 47 minutes (26%; 95% CI, −42 to −6) and mortality rates at 90 days were lower (adjusted odds ratio, 0.36; [95% CI: 0.13–1.00]) in the direct aspiration group. Conclusions This study shows no difference in favorable functional outcome in patients with a basilar artery occlusion treated with direct aspiration compared with patients treated with stent retriever thrombectomy within the BASICS trial, despite a shorter procedure time and lower mortality rate at 90 days.

Background During the past few decades, several pathophysiological processes contributing to intracranial aneurysm (IA) rupture have been identified, including irregular IA shape, altered hemodynamic stress within the IA, and vessel wall inflammation. The use of preclinical models of IA and imaging tools is paramount to better understand the underlying disease mechanisms. Methods We used 2 established mouse models of IA, and we analyzed the progression of the IA by magnetic resonance imaging, transcranial Doppler, and histology. Results In both models of IA, we observed, by transcranial Doppler, a significant decrease of the blood velocities and wall shear stress of the internal carotid arteries. We also observed the formation of tortuous arteries in both models that were correlated with the presence of an aneurysm as confirmed by magnetic resonance imaging and histology. A high grade of tortuosity is associated with a significant decrease of the mean blood flow velocities and a greater artery dilation. Conclusions Transcranial Doppler is a robust and convenient imaging method to evaluate the progression of IA. Detection of decreased blood flow velocities and increased tortuosity can be used as reliable indicators of IA.

Background The association between time to reperfusion and clinical outcome is well known in anterior circulation strokes, whereas the impact of main time metrics remains unknown in posterior circulation strokes. We investigated the clinical effect of different time intervals from symptom onset to reperfusion on the 90‐day clinical outcome in acute ischemic stroke patients with basilar artery occlusion, and especially in the subset population presenting a low stroke volume on baseline diffusion‐weighted imaging. Methods and Results We studied patients included in the prospective, multicenter, observational ETIS (Endovascular Treatment in Ischemic Stroke) registry who had had basal artery occlusion and had achieved successful reperfusion (modified Thrombolysis In Cerebral Infarction 2b‐3). Three time intervals (onset to reperfusion, onset to imaging, and imaging to reperfusion) were considered in all patients and separately in patients with pc‐ASPECTS (posterior‐circulation Alberta Stroke Program Early Computed Tomography Score)

Background Studies on the role of blood pressure (BP) variability specifically during mechanical thrombectomy (MT) are sparse and limited. Moreover, pulse pressure (PP) has not been considered as a potent hemodynamic parameter to describe BP variability during MT. We assessed the impact of PP variability on functional outcome in acute ischemic stroke patients with large vessel occlusion during MT. Methods and Results Acute ischemic stroke patients presenting with large vessel occlusion from January 2012 to June 2016 were included. BP data during MT were prospectively collected in the ETIS (Endovascular Treatment in Ischemic Stroke) registry. Logistic regression models were used to assess the association between PP coefficients of variation and functional outcome at 3 months (modified Rankin Scale). Among the 343 included patients, PP variability was significantly associated with worse 3‐month modified Rankin Scale in univariable (odds ratio [OR]=1.56, 95% confidence interval [CI]: 1.24–1.96 per 1‐unit increase, P=0.0002) and multivariable ordinal logistic regression (adjusted OR=1.40, 95% CI: 1.09–1.79, P=0.008). PP variability was also associated with unfavorable outcome (modified Rankin Scale 3–6) in univariable (OR=1.53, 95% CI: 1.17–2.01, P=0.002) and multivariable analysis (adjusted OR=1.42, 95% CI: 1.02–1.98, P=0.04). There was an association between PP variability and 3‐month all‐cause mortality in univariable analysis (OR= 1.37, 95% CI: 1.01–1.85 per 1‐unit increase of the coefficient of variation of the PP, P=0.04), which did not remain significant after adjustment for potential confounders. Conclusions PP variability during MT is an independent predictor of worse clinical outcome in acute ischemic stroke patients. These findings support the need for a close monitoring of BP variability during MT. Whether pharmacological interventions aiming at reducing BP variability during MT could impact functional outcome needs to be determined.

BackgroundPrevious experimental studies have shown that downstream microvascular thromboinflammation is involved in brain damage from acute ischemic stroke. Using intravital microscopy, we investigated and characterized the sequence of downstream microvascular thromboinflammation in an ischemia/reperfusion acute ischemic stroke model. Methods and ResultsRats underwent transient monofilament middle cerebral artery (MCA) occlusion. Cerebral microcirculation in the MCA territory was exposed through a craniotomy and analyzed using real‐time intravital imaging coupled with laser Doppler interferometry. Leukocytes, platelets, fibrinogen, and blood–brain barrier permeability were analyzed by intravenous injection of fluorescent antibodies and bovine serum albumin. MCA occlusion induced a sudden and profound drop in downstream microvascular blood flow associated with leukocyte margination in the venous compartment. Leukocyte margination fostered fibrinogen deposition and thrombosis in postcapillary venules. Either in venules or arterioles, blood flow was not fully restored after MCA recanalization. Furthermore, venular thrombi persisted despite MCA recanalization, and leukocyte extravasation continued to develop in venules in association with blood–brain barrier disruption. Finally, microhemorrhages were occasionally observed, colocalizing with thrombosed venules characterized by marked leukocyte margination. ConclusionsWe showed that microvascular thrombosis in transient monofilament MCA occlusion and blood–brain barrier disruption are initiated immediately after occlusion and are propagated through the venous compartment in close association with marginating leukocytes. MCA occlusion–induced downstream microvascular thromboinflammation response was responsible for incomplete reperfusion after MCA recanalization and delayed microhemorrhages.

BackgroundHigh blood pressure (BP) is associated with worse clinical outcomes in the setting of acute ischemic stroke, but the optimal blood pressure target is still a matter of debate. We aimed to study the association between baseline BP and mortality in acute ischemic stroke patients treated by mechanical thrombectomy. Methods and ResultsA total of 1332 acute ischemic stroke patients treated by mechanical thrombectomy were enrolled (from January 2012 to June 2016) in the ETIS (Endovascular Treatment in Ischemic Stroke) registry. Linear and polynomial logistic regression models were used to assess the association between BP and mortality and functional outcome at 90 days. Highest mortality was found at lower and higher baseline systolic blood pressure (SBP) values following a J‐ or U‐shaped relationship, with a nadir at 157 mm Hg (95% confidence interval 143‐170). When SBP values were categorized in 10–mm Hg increments, the odds ratio for all‐cause mortality was 3.78 (95% confidence interval 1.50‐9.55) for SBP

BackgroundExamination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12‐month follow‐up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke) III Trial. Methods and ResultsProspective data collected for a prespecified economic analysis of the trial were used. Data included hospital billing records for the initial stroke admission and subsequent detailed resource use after the acute hospitalization collected at 3, 6, 9, and 12 months. Cost of follow‐up care varied 6‐fold for patients in the lowest (0–1) and highest (20+) National Institutes of Health Stroke Scale category at 5 days, and by modified Rankin Scale at 3 months. The kind of resources used postdischarge also varied between treatment groups. Incremental short‐term cost‐effectiveness ratios varied greatly when treatments were compared for patient subgroups. Patient subgroups predefined by stroke severity had incremental cost‐effectiveness ratios of $97 303/quality‐adjusted life year (severe stroke) and $3 187 805/quality‐adjusted life year (moderately severe stroke). ConclusionsDetailed economic and resource utilization data from IMS III provide powerful evidence for the large effect that patient outcome has on the economic value of medical and endovascular reperfusion therapies. These data can be used to inform process improvements for stroke care and to estimate the cost‐effectiveness of endovascular therapy in the US health system for stroke intervention trials. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Registration number: NCT00359424.