The pathophysiological mechanisms of Moyamoya angiopathy (MA), which is a rare cerebrovascular condition characterized by recurrent ischemic/hemorrhagic strokes, are still largely unknown. An ...imbalance of vasculogenic/angiogenic mechanisms has been proposed as one possible disease aspect. Circulating endothelial progenitor cells (cEPCs) have been hypothesized to contribute to vascular remodeling of MA, but it remains unclear whether they might be considered a disease effect or have a role in disease pathogenesis. The aim of the present study was to provide a morphological, phenotypical, and functional characterization of the cEPCs from MA patients to uncover their role in the disease pathophysiology. cEPCs were identified from whole blood as CD45
CD34
CD133
mononuclear cells. Morphological, biochemical, and functional assays were performed to characterize cEPCs. A significant reduced level of cEPCs was found in blood samples collected from a homogeneous group of adult (mean age 46.86 ± 11.7; 86.36% females), Caucasian, non-operated MA patients with respect to healthy donors (HD;
= 0.032). Since no difference in cEPC characteristics and functionality was observed between MA patients and HD, a defective recruitment mechanism could be involved in the disease pathophysiology. Collectively, our results suggest that cEPC level more than endothelial progenitor cell (EPC) functionality seems to be a potential marker of MA. The validation of our results on a larger population and the correlation with clinical data as well as the use of more complex cellular model could help our understanding of EPC role in MA pathophysiology.
Background and purpose
The embolic stroke of undetermined source (ESUS) represents a heterogeneous clinical entity. The aim of this study was to investigate whether distinct clinical phenotypes may ...be identified in the ESUS population.
Methods
We retrospectively identified consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria. Baseline characteristics and diagnostic workup findings were collected. Hierarchical cluster analysis was carried out to classify clinical features and identify different groups of ESUS patients.
Results
One hundred twenty-seven patients with a mean age of 68.6 (12.5) years were included. Three main clusters were identified. The first cluster associated young age, male sex, presence of patent foramen ovale, and posterior circulation infarct. The second phenotype linked hypertension, severe stroke, left atrial cardiopathy, diabetes mellitus, and involvement of multiple vascular territories. The third cluster gathered smoking, dyslipidemia, ipsilateral vulnerable sub-stenotic carotid plaque, and infarct of anterior vascular territory.
Conclusions
Distinct clinical phenotypes have been identified within the ESUS population, which may supply clues to the underlying pathogenic mechanisms.
The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns ...likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly.
In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS European Cooperative Acute Stroke Study-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models.
Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratio
1.14 0.83-1.57) did not differ significantly between both groups. However, the probability of death (odds ratio
3.77 3.14-4.53) and poor functional outcome (odds ratio
2.63 2.13-3.25) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar.
The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.
Inflammatory mediators and metalloproteinases are altered in acute ischemic stroke (AIS) and play a detrimental effect on clinical severity and hemorrhagic transformation of the ischemic brain ...lesion. Using data from the Italian multicenter observational MAGIC (MArker bioloGici nell’Ictus Cerebrale) Study, we evaluated the effect of inflammatory and metalloproteinases profiles on three-month functional outcome, hemorrhagic transformation and mortality in 327 patients with AIS treated with intravenous thrombolys in according to SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy) criteria. Circulating biomarkers were assessed at baseline and 24 h after thrombolysis. Adjusting for age, sex, baseline glycemia and National Institute of Health Stroke Scale, history of atrial fibrillation or congestive heart failure, and of inflammatory diseases or infections, baseline alpha-2macroglobulin (A2M), baseline serum amyloid protein (SAP) and pre-post tissue-plasminogen activator (tPA) variations (Δ) of metalloproteinase 9, remained significantly and independently associated with three-month death OR (95% CI):A2M:2.99 (1.19–7.53); SAP:5.46 (1.64–18.74); Δmetalloproteinase 9:1.60 (1.12–2.27). The addition of baseline A2M and Δmetalloproteinase 9 or baseline SAP and Δmetalloproteinase 9 (model-2 or model-3) to clinical variables (model-1) significantly improved the area under curve for prediction of death model-2 with A2M: p = 0.0205; model-3 with SAP: p = 0.001. In conclusion, among AIS patients treated with thrombolysis, circulating A2M, SAP and Δmetalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.
Prediction of Outcome in Embolic Strokes of Undetermined Source Lattanzi, Simona; Pulcini, Alessandra; Corradetti, Tommaso ...
Journal of stroke and cerebrovascular diseases,
January 2020, 2020-Jan, 2020-01-00, 20200101, Letnik:
29, Številka:
1
Journal Article
Recenzirano
Predicting outcome after stroke is a major goal and research field. The Embolic Stroke of Undetermined Source (ESUS) is a recently introduced clinical construct, and the prediction of outcome in this ...population has to be further explored. The aim of the study was to evaluate the prognostic validity and accuracy of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score in patients with ESUS.
Consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria were identified and the ASTRAL scores estimated. The study endpoint was the 3-month unfavorable outcome (modified Rankin Scale>2). Predictive performance was investigated through logistic regression analysis and discrimination and calibration tests.
Among 202 patients with ESUS, 67 (33.2%) had unfavourable 3-month outcome. The ASTRAL score was an independent predictor of poor outcome adjOR = 1.44, 95% confidence interval (CI) 1.30-1.60, P < .001, showed good discriminatory power (area under the receiver operating characteristic curve .913, 95% CI .871-.956) and was well calibrated (Hosmer-Lemeshow test P = .496).
The ASTRAL score was an independent predictor of 3-month functional outcome and showed high predictive accuracy in patients with ESUS.
Systematic reviews call for well-designed trials with clearly described intervention components to support the effectiveness of educational campaigns to reduce patient delay in stroke presentation. ...We herein describe the systematic development process of a campaign aimed to increase stroke awareness and preparedness.
Campaign development followed Intervention Mapping (IM), a theory- and evidence-based tool, and was articulated in two phases: needs assessment and intervention development. In phase 1, two cross-sectional surveys were performed, one aiming to measure stroke awareness in the target population and the other to analyze the behavioral determinants of prehospital delay. In phase 2, a matrix of proximal program objectives was developed, theory-based intervention methods and practical strategies were selected and program components and materials produced.
In phase 1, the survey on 202 citizens highlighted underestimation of symptom severity, as in only 44% of stroke situations respondents would choose to call the emergency service (EMS). In the survey on 393 consecutive patients, 55% presented over 2 hours after symptom onset; major determinants were deciding to call the general practitioner first and the reaction of the first person the patient called. In phase 2, adult individuals were identified as the target of the intervention, both as potential "patients" and witnesses of stroke. The low educational level found in the patient survey called for a narrative approach in cartoon form. The family setting was chosen for the message because 42% of patients who presented within 2 hours had been advised by a family member to call EMS. To act on people's tendency to view stroke as an untreatable disease, it was decided to avoid fear-arousal appeals and use a positive message providing instructions and hope. Focus groups were used to test educational products and identify the most suitable sites for message dissemination.
The IM approach allowed to develop a stroke campaign integrating theories, scientific evidence and information collected from the target population, and enabled to provide clear explanations for the reasons behind key decisions during the intervention development process.
NCT01881152 . Retrospectively registered June 7 2013.
Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. ...Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course are still under investigation. The incomplete knowledge of the disease limits the implementation of evidence-based guidelines on patient’s clinical management and the development of treatments able to prevent or reduce disease progression. The SENECA (SEarchiNg biomarkErs of Cerebral Angiopathy) project is the first Italian multicenter cohort study aimed at better defining the disease natural history and identifying clinical and neuroradiological markers of disease progression. By a multidisciplinary approach and the collection of a large and well-phenotyped series and biorepository of CAA patients, the study is ultimately expected to improve the diagnosis and the knowledge of CAA pathophysiological mechanisms.
Background
GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and ...research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results.
Methods
Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies.
Results
Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed.
Conclusion
An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy.
Spontaneous intracerebral hemorrhage (ICH) is a devastating type of stroke with a huge impact on patients and families. Expanded use of oral anticoagulants and ageing population might contribute to ...an epidemiological change. In view of these trends, we planned a study to obtain a contemporary picture and identify early prognostic factors to improve secondary prevention.
This multicenter prospective cohort study included consecutive adult patients with non-traumatic ICH admitted to three academic Italian hospitals (Salerno, Padova, Reggio Emilia) over a 2-year period. Demographic characteristics, vascular risk profile, clinical data and main radiological characteristics were correlated to 90-day clinical outcome.
Out of 682 patients mean age: 73 ± 14 years; 316 (46.3%) females enrolled in this study, 40% died 86/180 (47.8%) in Salerno, 120/320 (37.5%) in Padova, 67/182 (36.8%) in Reggio Emilia; p < 0.05) and 36% were severely disabled at 90 days. Several factors were associated with a higher risk of poor functional outcome such as antithrombotic drug use, hyperglycemia, previous cerebrovascular accident, low platelet count, and pontine/massive/intraventricular hemorrhage. However, at multivariate analysis only pre-ICH mRS score (OR 30.84), GCS score at presentation (OR 11.88), initial hematoma volume (OR 29.71), and NIHSS score at presentation (OR 25.89) were independent predictors of death and poor functional outcome.
Despite the heterogeneity among centers, this study on ICH has identified four simple prognostic factors that can independently predict patients outcome, stratify their risk, and guide their management.
The aim of this study was to investigate the prognostic role of hematoma characteristics and hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (ICH).
This multicenter ...prospective cohort study enrolled consecutive adult patients with non-traumatic ICH admitted to three Italian academic hospitals (Salerno, Padova, Reggio Emilia) over a 2-year period. Early noncontrast CT (NCCT) features of the hematoma, including markers of HE, and 3-month outcome were recorded. Multivariable logistic regression analysis was performed to identify predictors of poor outcome.
A total of 682 patients were included in the study mean age: 73 ± 14 years; 316 (46.3%) females. Pontine and massive hemorrhage, intraventricular bleeding, baseline hematoma volume > 15 mL, blend sign, swirl sign, margin irregularity ≥ 4, density heterogeneity ≥ 3, hypodensity ≥ 1, island sign, satellite sign, and black hole sign were associated with a higher risk of mortality and disability. However, at multivariate analysis only initial hematoma volume (OR 29.71) proved to be an independent predictor of poor functional outcome at 3 months.
Simple hematoma volume measured on baseline CT best identifies patients with a worse outcome, while early NCCT markers of HE do not seem to add any clinically significant information.
PDF
