Cryptogenic stroke as a working diagnosis: the need for an early and comprehensive diagnostic work-up

Atrial fibrillation; Cryptogenic stroke; Implantable cardiac monitorFibril·lació auricular; Ictus criptogènic; Monitor cardíac implantableFibrilación auricular; Ictus criptogénico; Monitor cardiaco implantableIn the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study, the causes of ischemic stroke were identified in 43% of cryptogenic stroke patients monitored with implantable cardiac monitor (ICM), but one-third of these patients had non-cardioembolic causes. These results suggest the need for an early and comprehensive diagnostic work-up before inserting an ICM

Exploring sex differences for acute ischemic stroke clinical, imaging and thrombus characteristics in the INTERRSeCT study

Stroke; Menopause; ThrombusIctus; Menopausia; TromboIctus; Menopausa; TrombeWomen, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of estrogen. Using the INTERRseCT cohort, a multicentre international observational cohort studying recanalization in acute ischemic stroke, we explored the effects of sex, and modifying effects of age, on neuroradiological predictors of recanalization including robustness of leptomeningeal collaterals, thrombus burden and thrombus permeability. Ordinal regression analyses were used to examine the relationship between sex and each of the neuroradiological markers. Further, we explored both multiplicative and additive interactions between age and sex. All patients (n = 575) from INTERRseCT were included. Mean age was 70.2 years (SD: 13.1) and 48.5% were women. In the unadjusted model, female sex was associated with better collaterals (OR 1.37, 95% CIs: 1.01-1.85), however this relationship was not significant after adjusting for age and relevant comorbidities. There were no significant interactions between age and sex. In a large prospective international cohort, we found no association between sex and radiological predictors of recanalization including leptomeningeal collaterals, thrombus permeability and thrombus burden.This prospective cohort study was funded by an operating grant from the Canadian Institutes of Health Research

Impact of Multiphase Computed Tomography Angiography for Endovascular Treatment Decision-Making on Outcomes in Patients with Acute Ischemic Stroke

Cerebrovascular circulation; Ischemia; Ischemic strokeCirculació cerebrovascular; Isquèmia; Ictus isquèmicCirculación cerebrovascular; Isquemia; Ictus isquémicoBackground and Purpose Various imaging paradigms are used for endovascular treatment (EVT) decision-making and outcome estimation in acute ischemic stroke (AIS). We aim to compare how these imaging paradigms perform for EVT patient selection and outcome estimation. Methods Prospective multi-center cohort study of patients with AIS symptoms with multi-phase computed tomography angiography (mCTA) and computed tomography perfusion (CTP) baseline imaging. mCTA-based EVT-eligibility was defined as presence of large vessel occlusion (LVO) and moderate-to-good collaterals on mCTA. CTP-based eligibility was defined as presence of LVO, ischemic core (defined on relative cerebral blood flow, absolute cerebral blood flow, and cerebral blood volume maps) 1.8, absolute mismatch >15 mL. EVT-eligibility and adjusted rates of good outcome (modified Rankin Scale 0-2) based on these imaging paradigms were compared. Results Of 289/464 patients with LVO, 263 (91%) were EVT-eligible by mCTA-criteria versus 63 (22%), 19 (7%) and 103 (36%) by rCBF, aCBF, and CBV-CTP-criteria. CTP and mCTA-criteria were discordant in 40% to 53%. Estimated outcomes were best in patients who met both mCTA and CTP eligibility-criteria and were treated with EVT (62% to 87% good outcome). Patients eligible for EVT by mCTA-criteria and not by CTP-criteria receiving EVT achieved good outcome rates of 53% to 57%. Few patients met CTP-criteria and not mCTA-criteria for EVT. Conclusions Simpler imaging selection criteria that rely on little else than detection of the occluded blood vessel may be more sensitive and less specific, thus resulting in more patients being offered EVT and arguably benefiting from it.This study was supported by a grant from the Canadian Institute of Health Research. The authors are most grateful to all enrolling sites

Stroke-associated pneumonia according to mCDC criteria: impact on prognosis and antibiotic therapy

Antibiotics; Infections; Stroke-associated pneumoniaAntibióticos; Infecciones; Neumonía asociada a ictusAntibiòtics; Infeccions; Pneumònia associada a ictusObjective: The modified Centers for Disease Control and Prevention (mCDC) criteria have been proposed for diagnosing and managing stroke-associated pneumonia (SAP). The objective was to investigate the impact of SAP on stroke outcome depending on whether or not it conforms to mCDC criteria. Our secondary objective was to identify the responsible factors for antibiotic initiation in stroke patients. Methods: We conducted a prospective, multicenter, observational study of ischemic stroke patients with moderate to severe stroke (NIHSS≥4) admitted within 24 h. For 7 days, mCDC criteria were assessed daily, and infections and antibiotics were recorded. Pneumonias were divided into those fulfilling mCDC criteria (mCDC-SAP) or not (other pneumonias, OPn). The effect of each type of pneumonia on 3-month outcome was evaluated in separated logistic regression models. Factors associated with antibiotic initiation were explored using a random forest analysis. Results: Of the 342 patients studied, infections were diagnosed in 72 (21.6%), including 39 (11.7%) cases of pneumonia. Of them, 25 (7.5%) fulfilled mCDC criteria. Antibiotics were used in 92% of mCDC-SAP and 64.3% of OPn. In logistic regression analysis, mCDC-SAP, but not OPn, was an independent predictor of poor outcome [OR, 4.939 (1.022–23.868)]. The random forest analysis revealed that fever had the highest importance for antibiotic initiation. Interpretation: The mCDC criteria might be useful for detecting clinically relevant SAP, which is associated with poor outcomes. Isolated signs of infection were more important for antibiotic initiation than compliance with pre-defined criteria. Therefore, adherence to mCDC criteria might result in antibiotic saving without compromising clinical outcome.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Study supported by Fundació La Marató de TV3 (201706-30-31), Instituto de Salud Carlos III (PI17/02130 and PI21/00949), co-financed by the Fondo Europeo de Desarrollo Regional. Some centres take part in Spanish Stroke Research Network RICORS-ICTUS (RD21/0006/0024, RD21/0006/0007 and RD21/0006/0015)

Blood Biomarker Panels for the Early Prediction of Stroke‐Associated Complications

Biomarkers; Stroke; Stroke‐associated infectionBiomarcadors; Ictus; Infecció associada a un ictusBiomarcadores; Ictus; Infección asociada a un ictusBackground Acute decompensated heart failure (ADHF) and respiratory tract infections (RTIs) are potentially life‐threatening complications in patients experiencing stroke during hospitalization. We aimed to test whether blood biomarker panels might predict these complications early after admission. Methods and Results Nine hundred thirty‐eight patients experiencing ischemic stroke were prospectively recruited in the Stroke‐Chip study. Post‐stroke complications during hospitalization were retrospectively evaluated. Blood samples were drawn within 6 hours after stroke onset, and 14 biomarkers were analyzed by immunoassays. Biomarker values were normalized using log‐transformation and Z score. PanelomiX algorithm was used to select panels with the best accuracy for predicting ADHF and RTI. Logistic regression models were constructed with the clinical variables and the biomarker panels. The additional predictive value of the panels compared with the clinical model alone was evaluated by receiver operating characteristic curves. An internal validation through a 10‐fold cross‐validation with 3 repeats was performed. ADHF and RTI occurred in 19 (2%) and 86 (9.1%) cases, respectively. Three‐biomarker panels were developed as predictors: vascular adhesion protein‐1 >5.67, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) >4.98 and d‐dimer >5.38 (sensitivity, 89.5%; specificity, 71.7%) for ADHF; and interleukin‐6 >3.97, von Willebrand factor >3.67, and d‐dimer >4.58 (sensitivity, 82.6%; specificity, 59.8%) for RTI. Both panels independently predicted stroke complications (panel for ADHF: odds ratio [OR] [95% CI], 10.1 [3–52.2]; panel for RTI: OR, 3.73 [1.95–7.14]) after adjustment by clinical confounders. The addition of the panel to clinical predictors significantly improved areas under the curve of the receiver operating characteristic curves in both cases. Conclusions Blood biomarkers could be useful for the early prediction of ADHF and RTI. Future studies should assess the usefulness of these panels in front of patients experiencing stroke with respiratory symptoms such as dyspnea.This project received funding from Instituto de Salud Carlos III (ISCIII) [DTS14/00004, PI17/02130], co‐financed by the European Regional Development Fund (FEDER), and from Fundació La Marató de TV3 [201706] and the European Union's Horizon 2020 research and innovation program [754517]. Neurovascular Research Laboratory takes part into the Spanish stroke research network INVICTUS+ (RD16/0019/0021). The funders had no role in the study design and conduction

Combined technique as first approach in mechanical thrombectomy: Efficacy and safety of REACT catheter combined with stent retriever

Acute stroke; Endovascular treatment; Mechanical thrombectomyAccidente cerebrovascular agudo; Tratamiento endovascular; Trombectomía mecánicaAccident cerebrovascular agut; Tractament endovascular; Trombectomia mecànicaIntroduction Mechanical thrombectomy (MT) with combined treatment including both a stent retriever and distal aspiration catheter may improve recanalization rates in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Here, we evaluated the effectiveness and safety of the REACT aspiration catheter used with a stent retriever. Methods This prospective study included consecutive adult patients who underwent MT with a combined technique using REACT 68 and/or 71 between June 2020 and July 2021. The primary endpoints were final and first pass mTICI 2b-3 and mTICI 2c-3 recanalization. Analysis was performed after first pass and after each attempt. Secondary safety outcomes included procedural complications, symptomatic intracranial hemorrhage (sICH) at 24 h, in-hospital mortality, and 90-day functional independence (modified Rankin Scale [mRS] 0–2). Results A total of 102 patients were included (median age 78; IQR: 73–87; 50.0% female). At baseline, median NIHSS score was 19 (IQR: 11–21), and ASPECTS was 9 (IQR: 8–10). Final mTICI 2b-3 recanalization was achieved in 91 (89.2%) patients and mTICI 2c-3 was achieved in 66 (64.7%). At first pass, mTICI 2b-3 was achieved in 55 (53.9%) patients, and mTICI 2c-3 in 37 (36.3%). The rate of procedural complications was 3.9% (4/102), sICH was 6.8% (7/102), in-hospital mortality was 12.7% (13/102), and 90-day functional independence was 35.6% (36/102). Conclusion A combined MT technique using a stent retriever and REACT catheter resulted in a high rate of successful recanalization and first pass recanalization in a sample of consecutive patients with AIS due to LVO in clinical use

Added value of patient-reported outcome measures (PROMs) after an acute stroke and early predictors of 90 days PROMs

Outcomes; Stroke; Value based health careResultats; Ictus; Atenció de la salut basada en valorsResultados; Ictus; Atención de la salud basado en valoresIntroduction Value-based health care represents a patient-centered approach by valuing Patient-Reported Outcome Measures (PROMs). Our aim was to describe the additional value of PROMs after an acute stroke over conventional outcome measures and to identify early predictors of poor PROMs. Methods Acute stroke patients discharged from a tertiary care hospital followed by a web/phone-based PROMs collection program in the post hospitalization phase. Main PROMs involve anxiety and depression (HADS) (each defined by HADS ≥ 10) and global physical (PHY-) and mental (M-) health (PROMIS-10). PROMIS cut-off raw values of normality were: PHY-PROMIS ≥ 13 and M-PROMIS ≥ 11. An overall health status (OHS) from 0 to 100 was also determined. PROMs related to the different modified Rankin Scale (mRS) grades were defined. Early predictors of PROMs were evaluated. Results We included 1321 stroke patients, mean age 75 (± 8.6) and 55.7% male; 77.7% returned home. Despite a favorable mRS at 3 months (< 3), a relevant rate of patients considered without symptoms or with mild disability showed unfavorable results in the measured PROMs (8% unfavorable OHS, 15% HAD-depression, 12.1% HAD-anxiety, 28.7% unfavorable M-PROMIS and 33.1% unfavorable PHY-PROMIS results). Along follow-up, only PHY-PROMIS and OHS showed significant improvement (p < 0.01 and 0.03, respectively). The multivariate analysis including discharge variables showed that female sex, higher discharge mRS and discharge to socio-rehabilitation-center (SRC) were independent predictors of unfavorable results in PROMs (p < 0.01). When adding 7 days PROMs results, they emerged as the strongest predictors of 3 months PROMs. Conclusions A high proportion of stroke patients show unfavorable results in PROMs at 3 months, even those with favorable mRS, and most results obtained by PROMs during follow-up continued to indicate alterations. Female sex, mRS and discharge to SRC predicted unfavorable results in PROMs, but the strongest predictors of 3 months PROMs were the results of the 7 days PROMs

Multiphase CT Angiography Improves Prediction of Intracerebral Hemorrhage Expansion

Angiography; Intracerebral hemorrhage; PredictionAngiografía; Hemorragia intracerebral; PredicciónAngiografia; Hemorràgia intracerebral; PrediccióPurpose To determine the prevalence of the spot sign and the accuracy of using the spot sign to predict intracerebral hemorrhage (ICH) expansion with standardized multiphase computed tomographic (CT) angiography. Materials and Methods This prospective observational cohort study included 123 consecutive patients with acute ICH (onset 33% or >6 mL) at 24 hours. Associations between the presence of the spot sign and substantial hematoma expansion were assessed by using the Pearson χ2 test. Results The later the phase of CT angiography, the higher the frequency of the spot sign. The spot sign was seen in 29.3% of patients in phase 1, 43.1% of patients in phase 2, and 46.3% of patients in phase 3 (P B > C > D > no spot sign (P = .002). Conclusion Multiphase CT angiography can help differentiate among different forms of spot sign presentation and can help stratify patients at risk for hematoma expansion. The more arterial the spot sign pattern, the greater the frequency and extent of expansion

Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes

Acute stroke; Flow cytometry; Mechanical thrombectomyIctus agut; Citometria de flux; Trombectomia mecànicaIctus agudo; Citometría de flujo; Trombectomía mecánicaWe aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01–1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson’s r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9–42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment.Open Access Funding provided by Universitat Autonoma de Barcelona. This work was supported by “Project 355/C/2017, Fundació La Marató de TV3 in Strokes and Traumatic Spinal Cord and Brain Injury, 2017 Call of Projects.

Blood Biomarker Panels for the Early Prediction of Stroke‐Associated Complications

Background Acute decompensated heart failure (ADHF) and respiratory tract infections (RTIs) are potentially life-threatening complications in patients experiencing stroke during hospitalization. We aimed to test whether blood biomarker panels might predict these complications early after admission. Methods and Results Nine hundred thirty-eight patients experiencing ischemic stroke were prospectively recruited in the Stroke-Chip study. Post-stroke complications during hospitalization were retrospectively evaluated. Blood samples were drawn within 6 hours after stroke onset, and 14 biomarkers were analyzed by immunoassays. Biomarker values were normalized using log-transformation and Z score. PanelomiX algorithm was used to select panels with the best accuracy for predicting ADHF and RTI. Logistic regression models were constructed with the clinical variables and the biomarker panels. The additional predictive value of the panels compared with the clinical model alone was evaluated by receiver operating characteristic curves. An internal validation through a 10-fold cross-validation with 3 repeats was performed. ADHF and RTI occurred in 19 (2%) and 86 (9.1%) cases, respectively. Three-biomarker panels were developed as predictors: vascular adhesion protein-1 >5.67, NT-proBNP (N-terminal pro-B-type natriuretic peptide) >4.98 and d-dimer >5.38 (sensitivity, 89.5%; specificity, 71.7%) for ADHF; and interleukin-6 >3.97, von Willebrand factor >3.67, and d-dimer >4.58 (sensitivity, 82.6%; specificity, 59.8%) for RTI. Both panels independently predicted stroke complications (panel for ADHF: odds ratio [OR] [95% CI], 10.1 [3-52.2]; panel for RTI: OR, 3.73 [1.95-7.14]) after adjustment by clinical confounders. The addition of the panel to clinical predictors significantly improved areas under the curve of the receiver operating characteristic curves in both cases. Conclusions Blood biomarkers could be useful for the early prediction of ADHF and RTI. Future studies should assess the usefulness of these panels in front of patients experiencing stroke with respiratory symptoms such as dyspnea