Marina Padroni

Serum osteopontin levels are upregulated and predict disability after an ischaemic stroke

After an acute ischaemic stroke (AIS), several inflammatory biomarkers have been investigated, but their predictive role on functional recovery remains to be validated. Here, we investigated the prognostic relevance of biomarkers related to atherosclerotic plaque calcification, such as osteopontin (OPN), osteoprotegerin (OPG) and the receptor activator of nuclear factor kappa‐B ligand (RANKL) in a cohort of patients with AIS (n = 90) during 90‐day follow‐up.

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment

Introduction The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. Methods 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. Results Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. Conclusions Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.

Admission CT perfusion may overestimate initial infarct core: the ghost infarct core concept.

Background Identifying infarct core on admission is essential to establish the amount of salvageable tissue and indicate reperfusion therapies. Infarct core is established on CT perfusion (CTP) as the severely hypoperfused area, however the correlation between hypoperfusion and infarct core may be time-dependent as it is not a direct indicator of tissue damage. This study aims to characterize those cases in which the admission core lesion on CTP does not reflect an infarct on follow-up imaging. Methods We studied patients with cerebral large vessel occlusion who underwent CTP on admission but received endovascular thrombectomy based on a non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS) >6. Admission infarct core was measured on initial cerebral blood volume (CBV) CTP and final infarct on follow-up CT. We defined ghost infarct core (GIC) as initial core minus final infarct >10 mL. Results 79 patients were studied. Median National Institutes of Health Stroke Scale (NIHSS) score was 17 (11–20), median time from symptoms to CTP was 215 (87–327) min, and recanalization rate (TICI 2b–3) was 77%. Thirty patients (38%) presented with a GIC >10 mL. GIC >10 mL was associated with recanalization (TICI 2b–3: 90% vs 68%; p=0.026), admission glycemia (<185 mg/dL: 42% vs 0%; p=0.028), and time to CTP (<185 min: 51% vs >185 min: 26%; p=0.033). An adjusted logistic regression model identified time from symptom to CTP imaging <185 min as the only predictor of GIC >10 mL (OR 2.89, 95% CI 1.04 to 8.09). At 24 hours, clinical improvement was more frequent in patients with GIC >10 mL (66.6% vs 39%; p=0.017). Conclusions CT perfusion may overestimate final infarct core, especially in the early time window. Selecting patients for reperfusion therapies based on the CTP mismatch concept may deny treatment to patients who might still benefit from reperfusion.

Leptin/adiponectin ratio predicts poststroke neurological outcome.

Different adipokines have been associated with atherosclerotic plaque rupture and cardiovascular events, such as acute ischaemic stroke (AIS). However, the potential role of these molecules in postischaemic brain injury remains largely unknown.

Decreased serum PCSK9 levels after ischaemic stroke predict worse outcomes.

Soluble mediators have been investigated to predict the prognosis of acute ischaemic stroke (AIS). Among them, proprotein convertase subtilisin/kexin type 9 (PCSK9) might have both clinical and pathophysiological relevance.

Anti-ApoA-1 IgG serum levels predict worse poststroke outcomes

Autoantibodies to apolipoprotein A‐1 (anti‐ApoA‐1 IgG) were shown to predict major adverse cardiovascular events and promote atherogenesis. However, their potential relationship with clinical disability and ischaemic lesion volume after acute ischaemic stroke (AIS) remains unexplored.

Anticoagulants Resumption after Warfarin-Related Intracerebral Haemorrhage: The Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy)

Whether to resume antithrombotic treatment after oral anticoagulant-related intracerebral haemorrhage (OAC-ICH) is debatable. In this study, we aimed at investigating long-term outcome associated with OAC resumption after warfarin-related ICH, in comparison with secondary prevention strategies with platelet inhibitors or antithrombotic discontinuation. Participants were patients who sustained an incident ICH during warfarin treatment (2002-2014) included in the Multicenter Study on Cerebral Hemorrhage in Italy. Primary end-point was a composite of ischemic stroke/systemic embolism (SE) and all-cause mortality. Secondary end-points were ischemic stroke/SE, all-cause mortality and major recurrent bleeding. We computed individual propensity score (PS) as the probability that a patient resumes OACs or other agents given his pre-treatment variables, and performed Cox multivariable analysis using Inverse Probability of Treatment Weighting (IPTW) procedure. A total of 244 patients qualified for the analysis. Unlike antiplatelet agents, OAC resumption was associated with a lower rate of the primary end-point (weighted hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.09-0.45), as well as of overall mortality (weighted HR, 0.17; 95% CI, 0.06-0.45) and ischemic stroke/SE (weighted HR, 0.19; 95% CI, 0.06-0.60) with no significant increase of major bleeding in comparison with patients receiving no antithrombotics. In the subgroup of patients with atrial fibrillation, OACs resumption was also associated with a reduction of the primary end-point (weighted HR, 0.22; 95% CI, 0.09-0.54), and the secondary end-point ischemic stroke/SE (weighted HR, 0.09; 95% CI, 0.02-0.40). In conclusion, in patients who have an ICH while receiving warfarin, resuming anticoagulation results in a favorable trade-off between bleeding susceptibility and thromboembolic risk.

Vulnerability to Infarction During Cerebral Ischemia in Migraine Sufferers

Background and Purpose— Cerebral hyperexcitability in migraine experiencers might sensitize brain tissue to ischemia. We investigated whether a personal history of migraine is associated with vulnerability to brain ischemia in humans. Methods— Multicenter cohort study of patients with acute ischemic stroke who underwent a brain computed tomography perfusion and were scheduled to undergo reperfusion therapy. In a case–control design, we compared the proportion of subjects with no-mismatch, the volume of penumbra salvaged, as well as the final infarct size in a group of patients with migraine and a group of patients with no history of migraine. Results— We included 61 patients with migraine (34 [55.7%] men; mean age, 52.2±15.1 years; migraine without aura/migraine with aura, 44/17) and 61 patients with no history of migraine. The proportion of no-mismatch among migraineurs was significantly higher than among nonmigraineurs (17 [27.9%] versus 7 [11.5%]; P=0.039) and was more prominent among patients with migraine with aura (6 [35.3%]; P=0.030) while it was nonsignificantly increased in patients with migraine without aura (11 [25.0%]; P=0.114). Migraine, especially migraine with aura, was independently associated with a no-mismatch pattern (odds ratio, 2.65; 95% CI, 0.95–7.41 for migraine; odds ratio, 5.54; 95% CI, 1.28–23.99 for migraine with aura), and there was a linear decrease of the proportion of patients with migraine with aura with increasing quartiles of mismatch volumes. Patients with migraine with aura had also smaller volumes of salvaged penumbra (9.8±41.2 mL) compared with patients with migraine without aura (36.4±54.1 mL) and patients with no migraine (45.1±55.0 mL; P=0.056). Conversely, there was no difference in final infarct size among the 3 migraine subgroups (P=0.312). Conclusions— Migraine is likely to increase individual vulnerability to ischemic stroke during the process of acute brain ischemia and might represent, therefore, a potential new therapeutic target against occurrence and progression of the ischemic damage.

CBV_ASPECTS Improvement over CT_ASPECTS on Determining Irreversible Ischemic Lesion Decreases over Time

The Alberta Stroke Program Early CT Score (ASPECTS) is a useful scoring system for assessing early ischemic signs on noncontrast computed tomography (CT). Cerebral blood volume (CBV) on CT perfusion defines the core lesion assumed to be irreversibly damaged. We aim to explore the advantages of CBV_ASPECTS over CT_ASPECTS in the prediction of final infarct volume according to time. Methods: Consecutive patients with anterior circulation stroke who underwent endovascular reperfusion according to initial CT_ASPECTS ≥7 were studied. CBV_ASPECTS was assessed blindly later on. Recanalization was defined as thrombolysis in cerebral ischemia score 2b-3. Final infarct volumes were measured on follow-up imaging. We compared ASPECTS on CBV and CT images, and defined ASPECTS agreement as: CT_ASPECTS - CBV_ASPECTS ≤1. Results: Sixty-five patients, with a mean age of 67 ± 14 years and a median National Institutes of Health Stroke Scale score of 16 (range 10-20), were studied. The recanalization rate was 78.5%. The median CT_ASPECTS was 9 (range 8-10), and the CBV_ASPECTS was 8 (range 8-10). The mean time from symptoms to CT was 219 ± 143 min. Fifty patients (76.9%) showed ASPECTS agreement. The ASPECTS difference was inversely correlated to the time from symptoms to CT (r = -0.36, p < 0.01). A ROC curve defined 120 min as the best cutoff point after which the ASPECTS difference becomes more frequently ≤1. After 120 min, 89.5% of the patients showed ASPECTS agreement (as compared with 37.5% for <120 min, p < 0.01). CBV_ASPECTS but not CT_ASPECTS correlated with final infarct (r = -0.33, p < 0.01). However, if CT was done >2 h after symptom onset, CT_ASPECTS also correlated to final infarct (r = -0.39, p = 0.01). Conclusions: In acute stroke, CBV_ASPECTS correlates with the final infarct volume. However, when CT is performed after 120 min from symptom onset, CBV_ASPECTS does not add relevant information to CT_ASPECTS.

Monocyte count at onset predicts poststroke outcomes during a 90-day follow-up

Acute ischaemic stroke (AIS) triggers both systemic and neurovascular inflammation, influencing poststroke recovery. In smokers with AIS, inflammation might be further upregulated, increasing ischaemia/reperfusion injury. Here, the predictive value of leucocyte and adhesion molecules levels on poststroke outcomes was investigated.