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Background: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. Methods: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am –8:59 pm ) and nighttime (9:00 pm –7:59 am ). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. Results: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR], 1.620 [95% CI, 1.020–2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680–1.163]; P interaction =0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548–1.072]; nighttime, acOR, 1.785 [95% CI, 1.024–3.112] ; P interaction P interaction >0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. Conclusions: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.

Background: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2–5] versus 3 [1–5], common odds ratio, 1.25 [95% CI, 1.06–1.48]); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08–1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81–1.28]). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16–1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51–0.75]), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25–52]) and thrombectomy(mean difference 66 minutes [95% CI, 37–95]). Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.

BACKGROUNDThe risk prediction of stroke recurrence for individual patients is a difficult task. Individualised prediction may enhance stroke survivors selfcare engagement. We have developed PRERISK: a statistical and Machine Learning (ML) classifier to predict individual stroke recurrence risk.METHODSWe analysed clinical and socioeconomic data from a prospectively collected public healthcare-based dataset of 44623 patients admitted with stroke diagnosis in 88 public hospitals over 6 years in Catalonia-Spain. We trained several supervised-ML models to provide individualised risk along time and compared them with a Cox regression model.RESULTSOverall, 16% of patients presented a stroke recurrence along a median follow-up of 2.65 years. Models were trained for predicting early, late and long-term recurrence risk, within 90, 91-365 and >365 days, respectively. Most powerful predictors of stroke recurrence were time since index stroke, Barthel index, atrial fibrillation, dyslipidemia, haemoglobin and body mass index, which were used to create a simplified model with similar performance. The balanced AUROC were 0.77 (±0.01), 0.61 (±0.01) and 0.71 (±0.01) for early, late and long-term recurrence risk respectively (Cox risk class probability: 0.74(±0.01), 0.59(±0.01) and 0.68(±0.01), c-index 0.88). Overall, the ML approach showed statistically significant improvement over the Cox model. Stroke recurrence curves can be simulated for each patient under different degrees of control of modifiable factors.CONCLUSIONPRERISK represents a novel approach that provides continuous, personalised and fairly accurate risk prediction of stroke recurrence along time according to the degree of modifiable risk factors control.CLINICAL PERSPECTIVEWhat is new?Stroke recurrence is frequent after stroke despite advances in stroke treatments, and it is difficult to predict the individual risk of one patient.We have created PRERISK, a predictive model based on machine learning (ML) which provides individualised information of the probability of stroke recurrence and can be re-calculated according to risk factors control.What are the clinical implications?PRERISK information can be used as feedback for secondary prevention strategies and enhance patient engagement and treatment compliance.It could be scalable to optimise ML-based prevention strategies in other chronic conditions.

Background and Purpose: The potential benefit of blood pressure (BP) lowering in intracerebral hemorrhage (ICH) patients is time-dependent and is an easy and modifiable treatment applicable to different hospital scenarios. However, previous clinical trials did not establish consensus about the best BP strategy to achieve a rapid and sustained BP control. We aimed to assess the impact of learning a staged implementation of rapid-intensive-sustained BP protocol on time targets and BP control rate over the first 24 hours of ICH. Methods: We conducted a retrospective analysis of data prospectively collected of consecutive patients with spontaneous ICH (150 mmHg under a rapid (antihypertensive IV bolus by a stroke nurse at CT scan), intensive (SBP target Results: A total of 207 patients were included in the study. Compared between the periods, the frequency of SBP target achievement during the first hour was increased steadily over different periods(33.3% vs. 54.5% vs. 69.2% vs 69.4% vs 75% and 59.7%; P=0.024 ); median time to SBP target achievement tended to be lower during the evolution of protocol assessment (120 [45-240] min; 49.5 [30-101] min; 53 [29-82] min; 47 [28-74] min; 48 [27-66] min; 50 [30-85] min; P=0.054 ) and SBP sustention rate below the target improve during the acute phase at different time frames, including 2h (26.3% vs. 71.9% vs 60% vs 73.9% vs. 57,7% vs 59.5%; P= 0.012 ), 4h (57.1% vs. 63.3% vs 87.5% vs 85% vs. 61.5% vs. 69.2%; P= 0.05 ), 6h (60.9% vs. 58.6%, vs 95.5% vs 84.4% vs 58.3% vs. 75%; P=0.009 ). Conclusions: Rapid-intensive-sustained BP protocol is a good intervention to both achieve a rapid BP target and reduce time delays,and improve the rates of BP control over the acute phase of ICH patients.

Hypothesis: We aim to identify a profile of intracranial thrombus resistant to recanalization by standard mechanical thrombectomy (MT) in acute stroke treatment. Methods: First extracted clot of each MT were analyzed by Flow Cytometry obtaining composition of 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 after standard MT. In other cohort of cases, unconfined compression tests were performed to explore stiffness of retrieved clots . We looked for correlation between mechanical characterization tests and clot composition. Results: Among 225 patients, there were 13 % of MTF that were significantly associated to atherosclerosis etiology ( 33.3% vs. 15.9% ; p 0.021) , more passes ( 3 vs. 2; p Conclusions: There is a positive correlation between granulocyte proportion and thrombi stiffness that may explain endovascular resistance to recanalization. Influence of granulocytes within thrombus may be a target for future reperfusion treatments.

Objective: To assess whether the effect of intravenous thrombolysis in patients with large-vessel occlusion differed between patients directly admitted to thrombectomy-capable centers and patients transferred from local stroke centers without thrombectomy capabilities. Methods: We included 3206 patients with an acute ischemic large-vessel stroke with first imaging within 7 hours after onset that were directly admitted to thrombectomy-capable centers and treated with thrombectomy, or transferred from local stroke centers for thrombectomy evaluation, between 2017 and 2021 in Catalonia, Spain. Primary outcome was the degree of disability at 90 days, as evaluated by the shift analysis on the mRs score. Secondary outcomes included mortality at 90 days and the rate of parenchymal hemorrhage and successful reperfusion. Inverse-probability weighting clustered at the type of stroke center was used to estimate the effects. Results: The analysis included 2268 patients (975[49%] treated with thrombolysis) directly admitted to thrombectomy-capable centers and 938 patients (580[66%] treated with thrombolysis and 616[67%] treated with thrombectomy) transferred from local stroke centers (mean age 72±13 years, median NIHSS score 17[IQR 12-21], 1363 female[48%]). Patients treated with intravenous thrombolysis were younger, had shorter time from onset to first image acquisition, and higher rates of wake-up stroke, atrial fibrillation and anticoagulation intake. The effect of intravenous thrombolysis on the primary outcome was similar in patients directly admitted to thrombectomy-capable centers (acOR 1.50, 95% CI 1.24-1.81) and patients transferred from local stroke centers (acOR 1.44, 95% CI 1.04 to 2.01)(p interaction =0.68). Patients treated with intravenous thrombolysis had lower mortality rate, higher rate of parenchymal hematoma and similar rate of successful reperfusion, with no difference according to type of center (p interaction >0.1). Conclusion: Administration of intravenous thrombolysis in patients with a large-vessel stroke with intention to thrombectomy was associated with higher odds of good functional outcome and higher rates of parenchymal hematoma, independently of the type of stroke center were it was administered.

Background and Aims: The rising pressure on medical services, highlighted throughout the pandemic, has revealed a need for alternative methods of hospital care. Our objective is to evaluate a home hospitalization virtual multimodal monitoring program (NORAHOME) for patients who have had a previous transient ischemic attack (TIA) or minor stroke, as an efficient strategy compared to Routine Clinical Practice (RCP). Methods: A prospective cohort study of consecutive patients with a suspected TIA or minor stroke evaluated at the emergency room of a tertiary hospital by a neurologist between 1st December 2020 and 1st June 2022, had completed NORAHOME and was compared with a historic control group of patients with a suspected TIA or minor stroke who had completed a conventional hospitalization (RCP) between 1st June and 30th November 2020. Results: 430 patient cases were analyzed, 215 patients in the prospective group were compared with a retrospective cohort of the same number of patients. Mean age 75.21 ± 12.6 years; 54.9% women. In the NORAHOME group we observed a recurrence rate of 2.3% (5 patients) and mortality of 2.8% (6 patients) during the follow up. In the RCP group 6.5% (14 patients) presented recurrence and 7% (15 patients) died. No significant differences were found in the risk of early recurrence, emergency room readmission or functional outcome between the groups. Conclusions: In our series of TIA and minor stroke patients, NORAHOME is a safe strategy compared to RCP. The development and implementation of digital home-hospitalization programs may reduce direct hospital costs by shortening length of stay and reducing hospital readmission. Moreover, the program improves self-assessed health outcomes reported by patients and their experience with the healthcare system compared to the RCP.

Introduction: Recent publications suggest a positive added effect of iv-thrombolysis (IVT) in patients that undergo endovascular treatment (EVT). It is hypothesized that thrombolytics might have a beneficial impact on microcirculation beyond recanalization. We aim to analyze the potential impact of IVT in patients who underwent a repeated CTP after interhospital transfer. Methods: We retrospectively screened 116 patients transferred to our comprehensive stroke center from a primary stroke center capable to perform CTP from June 2021 to August 2022. We collected clinical and radiological data of patients that underwent CTP at both centers, which were analyzed with Rapid software. A neurointerventionalist assessed the occlusion location in CTA. Results: Twenty-eight patients with anterior circulation occlusion underwent two multimodal studies, median time between CTPs was 168[142-190]min. Fifteen (53.6%) patients received IVT in the primary stroke center and 13(46.4%) received EVT. Reperfusion occurred in 3(10.7%) cases, migration to distal segments in 5(17.9%). Among the 20 patients without changes in the occlusion location, CTP volumes remained stable (Tmax>6s 61[41-141]ml vs 62[24-178], p=0.72; Tmax>10s 19[8-96] vs 13[0-105], p=0.55; CBF30 0[0-66] vs 0[0-65], p=0.99). CTP volumes tended to decrease with IVT, but a modest increase was observed in patients that did not receive IVT (Tmax>6s -17[-29,+8]ml vs +22[-8,+42], p=0.08; Tmax>10s -8[-16,+6] vs +6[0,+37], p=0.10; CBF10s (p=0.06) and CBF Conclusion: In acute stroke patients with a LVO, no substantial changes are expected in CTP volumes in the absence of recanalization. However, patients that receive IVT tend to present reduced hypoperfusion volumes as compared with patients that do not receive IVT.

Background: Several noncontrast computed tomography (NCCT), single-phase computed tomography angiography (CTA), and multiphase CTA markers of intracerebral hemorrhage (ICH) expansion have been previously proposed. We derived and validated three scores for the prediction of hematoma expansion depending on the use of NCCT, single-phase CTA, or multiphase CTA markers of hematoma expansion. Methods: We prospective studied 276 consecutive patients with ICH within 6 hours from symptom onset. After deriving NCCT, single-phase CTA, and multiphase CTA scores in a 5-year period population (n=156), we validated them in a different 3-year period population (n=120). Outcome parameters included substantial hematoma expansion >6 mL or >33% at 24 hours (primary outcome) and poor outcome (mRS score >2) at 90 days. Results: The most accurate marker of hematoma expansion was spot sign in phase 1 of multiphase CTA (80.3%). The four independent predictors of substantial hematoma expansion included in the different scores were ultraearly hematoma growth (uHG) >5 mL/h, heterogeneous density, spot sign in phase 1 of multiphase CTA, and spot sign in any phase of multiphase CTA (Table). On each of the three scores, the proportion of patients that experienced substantial hematoma expansion increased with each point increase. C-index for both substantial hematoma expansion and poor outcome in the derivation and validation cohort was lower in NCCT expansion score than in single-phase CTA expansion score which, in turn, was lower than in multiphase CTA expansion score (Table). Conclusions: This study demonstrates the added prognostic value of more advanced CT modalities in acute ICH evaluation. Single-phase CTA score and, especially, multiphase CTA score, are more robust than NCCT score in the prediction of hematoma expansion and poor outcome. These scores may help to refine the selection of patients at risk of expansion and poorest outcomes in different decision-making scenarios.

BackgroundIn patients with stroke, current guidelines recommend non-invasive vascular imaging to identify intracranial vessel occlusions (VO) that may benefit from endovascular treatment (EVT). However, VO can be missed in CT angiography (CTA) readings. We aim to evaluate the impact of consistently including CT perfusion (CTP) in admission stroke imaging protocols.MethodsFrom April to October 2020 all patients admitted with a suspected acute ischemic stroke underwent urgent non-contrast CT, CTA and CTP and were treated accordingly. Hypoperfusion areas defined by time-to-maximum of the tissue residue function (Tmax) >6 s, congruent with the clinical symptoms and a vascular territory, were considered VO (CTP-VO). In addition, two experienced neuroradiologists blinded to CTP but not to clinical symptoms retrospectively evaluated non-contrast CT and CTA to identify intracranial VO (CTA-VO).ResultsOf the 338 patients included in the analysis, 157 (46.5%) presented with CTP-VO (median Tmax >6s: 73 (29–127) mL). CTA-VO was identified in 83 (24.5%) of the cases. Overall CTA-VO sensitivity for the detection of CTP-VO was 50.3% and specificity was 97.8%. Higher hypoperfusion volume was associated with increased CTA-VO detection (OR 1.03; 95% CI 1.02 to 1.04). EVT was performed in 103 patients (30.5%; Tmax >6s: 102 (63–160) mL), representing 65.6% of all CTP-VO. Overall CTA-VO sensitivity for the detection of EVT-VO was 69.9% and specificity was 95.3%. Among patients who received EVT, the rate of false negative CTA-VO was 30.1% (Tmax >6s: 69 (46–99.5) mL).ConclusionSystematically including CTP in acute stroke admission imaging protocols may increase the diagnosis of VO and rate of EVT.

Background and Purpose: Different studies have pointed that CT perfusion (CTP) could overestimate ischemic core in early time window. We aim to evaluate the influence of time and collateral status on ischemic core overestimation. Methods: Retrospective single-center study including patients with anterior circulation large-vessel stroke that achieved reperfusion after endovascular treatment. Ischemic core and collateral status were automatically estimated on baseline CTP using commercially available software. CTP-derived core was considered as tissue with a relative reduction of cerebral blood flow 6 seconds with time to maximum of tissue residue function >10 seconds). Final infarct volume was measured on 24 to 48 hours noncontrast CT. Ischemic core overestimation was considered when CTP-derived core was larger than final infarct. Results: Four hundred and seven patients were included in the analysis. Median CTP-derived core and final infarct volume were 7 mL (interquartile range, 0–27) and 20 mL (interquartile range, 5–55), respectively. Median hypoperfusion intensity ratio was 0.46 (interquartile range, 0.23–0.59). Eighty-three patients (20%) presented ischemic core overestimation (median overestimation, 12 mL [interquartile range, 41–5]). Multivariable logistic regression analysis adjusted by CTP-derived core and confounding variables showed that poor collateral status (per 0.1 hypoperfusion intensity ratio increase; adjusted odds ratio, 1.41 [95% CI, 1.20–1.65]) and earlier onset to imaging time (per 60 minutes earlier; adjusted odds ratio, 1.14 [CI, 1.04–1.25]) were independently associated with core overestimation. No significant association was found with imaging to reperfusion time (per 30 minutes earlier; adjusted odds ratio, 1.17 [CI, 0.96–1.44]). Poor collateral status influence on core overestimation differed according to onset to imaging time, with a stronger size of effect on early imaging patients( P interaction Conclusions: In patients with large-vessel stroke that achieve reperfusion after endovascular therapy, poor collateral status might induce higher rates of ischemic core overestimation on CTP, especially in patients in earlier window time. CTP reflects a hemodynamic state rather than tissue fate; collateral status and onset to imaging time are important factors to consider when estimating core on CTP.

Aim: We performed a histological and immune analysis of the clot in acute stroke patients to detect surrogates of stroke etiology. Methods: We conducted a prospective observational study of consecutive patients with acute stroke who underwent thrombectomy that obtained extracted thrombus (ITACAT study). Several staining were performed to evaluate red blood cells/fibrin (hematoxylin/eosin), platelets (CD61) and leucocytes (CD4, CD8 and CD20). All patients received CT angio to detect extra/intracranial vascular stenosis and 30-day cardiac monitoring to diagnose AF. According to TOAST classification the thrombi were classified in cardioembolic etiology CE (T-CE), due to symptomatic atherosclerosis (T-AT) and without any cause (T-CRYP). We excluded strokes due to double cause or incomplete workup. Results: Of the 117 patients: 30 were T-AT, 55 were T-CE and 32 were T-CRYP. T-AT patients were younger: T-AT 68 years (60-77) Vs. T-CE 75 years (68-80) Vs. T-CRYP 72 years (55-81) (p=0.034). T-AT group had higher percentage of CD4: T-AT 6.52% (4-13) Vs. T-CE (3.31% (12.9) Vs .T-CRYP 3.72% (1.5-12) (p=0.015) and lower percentage of CD61: T-AT 51.18% (34-68) Vs. CE 64.70% (19.56) Vs. CRYP 70.3% (19) (p=0.001). There were no correlation between CD4 and platelets. Both CD4 OR 1.05 (1-1.10) (p=0.020) and CD61 (OR 0.96 (0.94-0.98) (p=0.01) independently predicted T-AT from the age. Final analysis (n=400 cases) will be ended in September 2021. Conclusions: Patients with high percentage of CD4 and low percentage of CD61 are related to atherosclerosis etiology.

Background: Endovascular treatment (EVT) for acute ischemic stroke (AIS) between 6 to 24 hours is established as a standard of care among patients selected by multiparametric neuroimaging. Therefore, we aimed to explore neuroimaging parameters in late window AIS large vessel occlusion (LVO) patients and the association between findings in non-contrast computed tomography (NCCT) and multiparametric CT. Methods: We included consecutive AIS patients within 6-24 hours from symptoms onset with CTA-LVO. We studied potential associations between computed tomography mismatch defined by DAWN and/or DEFUSE-3 neuroimaging criteria (CTP-MM), infarct volume on CTP, and ASPECTS on NCCT. We also analyzed the association between neuroimaging parameters and outcome determined by 90-day mRS. Results: We included 206 patients, of which 176 (85.4%) presented CTP-MM and 184 (89.3%) presented with an ASPECTS ≥ 6 on admission. The rate of CTP-MM was 90.8% in patients with ASPECTS ≥ 6, as compared with 40.9% in those with low ASPECTS [Figure 1A] . The ASPECTS correlated with infarct core, determined by Cerebral Blood Flow [Figure 1B] . Conclusions: A great majority of patients who presented a LVO in late window fulfilled guidelines imaging criteria to undergo EVT, especially those with high ASPECTS (≥ 6). Our data suggest that NCCT with CT angiography is a reasonable approach for acute ischemic stroke treatment selection also in the late window.

Background and Purpose— Despite recanalization, almost 50% of patients undergoing endovascular treatment (EVT) experience poor outcome. We aim to evaluate the value of computed tomography perfusion as immediate outcome predictor postendovascular treatment. Methods— Consecutive patients receiving endovascular treatment who achieved recanalization (modified Thrombolysis in Cerebral Ischemia [mTICI] 2a-3) underwent computed tomography perfusion within 30 minutes from recanalization (CTPpost). Hypoperfusion was defined as the Tmax>6 second volume; hyperperfusion as visually increased cerebral blood flow/cerebral blood volume with reduced Tmax compared with unaffected hemisphere. Dramatic clinical recovery (DCR) was defined as 24-hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. Delayed recovery was defined as no-DCR with favorable outcome (modified Rankin Scale score 0–2) at 3 months. Results— We included 151 patients: median National Institutes of Health Stroke Scale score 16 (interquartile range, 10–21), median admission ASPECTS 9 (interquartile range, 8–10). Final recanalization was the following: mTICI2a 11 (7.3%), mTICI2b 46 (30.5%), and mTICI3 94 (62.3%). On CTPpost, 80 (52.9%) patients showed hypoperfusion (median Tmax>6 seconds: 4 cc [0–25]) and 32 (21.2%) hyperperfusion. There was an association between final TICI and CTPpost hypoperfusion(median Tmax>6: 91 [56–117], 15 [0–37.5], and 0 [0–7] cc, for mTICI 2a, 2b, and 3, respectively, P P P P P Conclusions— Hypoperfusion on CTPpost constitutes an immediate accurate surrogate marker of success after endovascular treatment and identifies those patients with delayed recovery and favorable outcome.

Background and Purpose— Definitions of significant hematoma expansion traditionally focus on changes in intraparenchymal volume. The presence of intraventricular hemorrhage (IVH) is a predictor of poor outcome, but current definitions of hematoma expansion do not include IVH expansion. We evaluated whether including IVH expansion to current definitions of hematoma expansion improves the ability to predict 90-day outcome. Methods— Using data from the PREDICT-ICH study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT), we compared a standard definition of hematoma expansion (≥6 mL or ≥33%) to revised definitions that includes new IVH development or expansion (≥6 mL or ≥33% or any IVH; ≥6 mL or ≥33% or IVH expansion ≥1 mL). The primary outcome was poor clinical outcome (modified Rankin Scale score, 4–6) at 90 days. Diagnostic accuracy measures were calculated for each definition, and C statistics for each definition were compared using nonparametric methods. Results— Of the 256 patients eligible for primary analysis, 127 (49.6%) had a modified Rankin Scale score of 4 to 6. Sensitivity and specificity for the standard definition (n=80) were 45.7% (95% CI, 36.8–54.7) and 82.9% (95% CI, 75.3–88.9), respectively. The revised definition, ≥6 mL or ≥33% or any IVH (n=113), possessed a sensitivity of 63.8% (95% CI, 54.8–72.1) and specificity of 75.2% (95% CI, 66.8–82.4). Overall accuracy was significantly improved with the revised definition ( P =0.013) and after adjusting for relevant covariates, was associated with a 2.55-fold increased odds (95% CI, 1.31–4.94) of poor outcome at 90 days. A second revised definition, ≥6 mL or ≥33% or IVH expansion ≥1 mL, performed similarly (sensitivity, 56.7% [95% CI, 47.6–65.5]; specificity, 78.3% [95% CI, 40.2–85.1]; aOR, 2.40 [95% CI, 1.23–4.69]). Conclusions— In patients with mild-to-moderate ICH, including IVH expansion to the definition of hematoma expansion improves sensitivity with only minimal decreases to specificity and improves overall prediction of 90-day outcome.

Background and Purpose— Patients with intracerebral hemorrhage (ICH) are often subject to rapid deterioration due to hematoma expansion. Current prognostic scores are largely based on the assessment of baseline radiographic characteristics and do not account for subsequent changes. We propose that calculation of prognostic scores using delayed imaging will have better predictive values for long-term mortality compared with baseline assessments. Methods— We analyzed prospectively collected data from the multicenter PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign). We calculated the ICH Score, Functional Outcome in Patients With Primary Intracerebral Hemorrhage (FUNC) Score, and modified ICH Score using imaging data at initial presentation and at 24 hours. The primary outcome was mortality at 90 days. We generated receiver operating characteristic curves for all 3 scores, both at baseline and at 24 hours, and assessed predictive accuracy for 90-day mortality with their respective area under the curve. Competing curves were assessed with nonparametric methods. Results— The analysis included 280 patients, with a 90-day mortality rate of 25.4%. All 3 prognostic scores calculated using 24-hour imaging were more predictive of mortality as compared with baseline: the area under the curve was 0.82 at 24 hours (95% CI, 0.76–0.87) compared with 0.78 at baseline (95% CI, 0.72–0.84) for ICH Score, 0.84 at 24 hours (95% CI, 0.79–0.89) compared with 0.76 at baseline (95% CI, 0.70–0.83) for FUNC, and 0.82 at 24 hours (95% CI, 0.76–0.88) compared with 0.74 at baseline (95% CI, 0.67–0.81) for modified ICH Score. Conclusions— Calculation of the ICH Score, FUNC Score, and modified ICH Score using 24-hour imaging demonstrated better prognostic value in predicting 90-day mortality compared with those calculated at presentation.

Malaltia d'Alzheimer; Biomarcadors; Microdissecció de captura làser Alzheimer's disease; Biomarkers; Laser capture microdissection Enfermedad de Alzheimer; Biomarcadores; Microdisección por captura láser Brain accumulation of amyloid-beta (Aβ) is a crucial feature in Alzheimer´s disease (AD) and cerebral amyloid angiopathy (CAA), although the pathophysiological relationship between these diseases remains unclear. Numerous proteins are associated with Aβ deposited in parenchymal plaques and/or cerebral vessels. We hypothesized that the study of these proteins would increase our understanding of the overlap and biological differences between these two pathologies and may yield new diagnostic tools and specific therapeutic targets. We used a laser capture microdissection approach combined with mass spectrometry in the APP23 transgenic mouse model of cerebral-β-amyloidosis to specifically identify vascular Aβ-associated proteins. We focused on one of the main proteins detected in the Aβ-affected cerebrovasculature: MFG-E8 (milk fat globule-EGF factor 8), also known as lactadherin. We first validated the presence of MFG-E8 in mouse and human brains. Immunofluorescence and immunoblotting studies revealed that MFG-E8 brain levels were higher in APP23 mice than in WT mice. Furthermore, MFG-E8 was strongly detected in Aβ-positive vessels in human postmortem CAA brains, whereas MFG-E8 was not present in parenchymal Aβ deposits. Levels of MFG-E8 were additionally analysed in serum and cerebrospinal fluid (CSF) from patients diagnosed with CAA, patients with AD and control subjects. Whereas no differences were found in MFG-E8 serum levels between groups, MFG-E8 concentration was significantly lower in the CSF of CAA patients compared to controls and AD patients. Finally, in human vascular smooth muscle cells MFG-E8 was protective against the toxic effects of the treatment with the Aβ40 peptide containing the Dutch mutation. In summary, our study shows that MFG-E8 is highly associated with CAA pathology and highlights MFG-E8 as a new CSF biomarker that could potentially be used to differentiate cerebrovascular Aβ pathology from parenchymal Aβ deposition. This work was funded by the Instituto de Salud Carlos III (ISCIII), (PI20/00465), co-financed by the European Regional Development Fund (FEDER). The Neurovascular Research Laboratory is part of the INVICTUS + network, ISCIII, Spain (RD16/0019/0021). P.M. held a predoctoral fellowship from the Vall d’Hebron Research Institute. MMV is supported by the BIONIC project (no. 733050822, which has been made possible by ZonMW as part of ‘Memorabel’, the research and innovation program for dementia, as part of the Dutch national ‘Deltaplan for Dementia’:the CAFÉ project (the National Institutes of Health, USA, grant number 5R01NS104147-02), and a grant from the Selfridges Group Foundation (NR170024). The BIONIC project is a consortium of Radboudumc, LUMC, ADX Neurosciences, and Rhode Island University.

Background and Purpose— Substantial proportion of patients who achieve successful recanalization of acute ischemic stroke due to large vessel occlusion do not achieve good functional outcome. We aim to analyze the effect of number of thrombectomy device passes and degree of the recanalization (by modified Thrombolysis in Cerebral Infarction) on the clinical and functional outcome. Methods— Five hundred forty-two consecutive patients underwent mechanical thrombectomy for large vessel occlusion in the anterior circulation at a single tertiary stroke center. Baseline characteristics, number of passes, recanalization degree, clinical outcome at 24 hours (measured by National Institutes of Health Scale score), and functional outcome (measured by modified Rankin Scale at 90 days) were registered. Multivariate analysis was performed to determine the association of number of passes and degree of recanalization with dramatical clinical recovery (final National Institutes of Health Scale score ≤2 or decrease in 8 or more National Institutes of Health Scale score points in 24 hours) and good functional outcome (modified Rankin Scale score ≤2 at 90 days). Results— Four hundred fifty-nine patients (84%) achieved successful recanalization (modified Thrombolysis in Cerebral Infarction 2B–3), 213 (39%) of them after first device pass. In the multivariate analysis, first-pass recanalization and modified Thrombolysis in Cerebral Infarction 3 were independent predictors of good functional outcome (odds ratio, 2.5; 95% CI, 1.4–4.5; P =0.002 and odds ratio, 2.6 CI; 1.5–4.7; P =0.001, respectively) and dramatical clinical recovery (odds ratio, 1.8; 95% CI, 1.1–3; P =0.032 and odds ratio, 2.9; 95% CI, 1.7–5.1; P P P Conclusions— High number of device passes and less degree of recanalization are associated with worse outcome in patients with acute ischemic stroke secondary to large vessel occlusion. Future studies should investigate the optimal number of passes that should be attempted in patients without substantial recanalization.

Background and Purpose— Risk factor control and treatment compliance in the following months after stroke are poor. We aim to validate a digital platform for smartphones to raise awareness among patients about the need to adopt healthy lifestyle, improve communication with medical staff, and treatment compliance. Methods— Farmalarm is an application (app) for smartphones designed to increase stroke awareness by medication alerts and compliance control, chat communication with medical staff, didactic video files, exercise monitoring. Patients with stroke discharged home were screened for participation and divided into groups: to follow the FARMALARM program for 3 to 4 weeks or standard of care follow-up. We determined achievement of risk factor control goals at 90 days. Results— From August 2015 to December 2016, from the 457 patients discharged home, 159 (34.8%) were included: Farmalarm (n=107); age 57±12, Control (n=52), age 59±10; without significant differences in baseline characteristics between groups. At 90 days, knowledge of vascular risk factors was higher in FARMALARM group (86.0% versus 69.2%, P P P =0.03) under control and the rate of patients with 4 out of 4 risk factors under control was higher in FARMALARM group (50.4% versus 30.7%, P =0.02). A regression model showed that the use of Farmalarm was independently associated with all risk factors under control at 90 days (odds ratio, 2.3; 95% CI, 1.14–4.6; P =0.02). Conclusions— In patients with stroke discharged home, the use of mobile apps to monitor medication compliance and increase stroke awareness is feasible and seems to improve the control of vascular risk factors.

The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01–1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57–0.71). Youden’s method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09–3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61–5.42) were similar to HEP scores ≥ 4. The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

Background and Purpose— Hyperglycemia is a negative prognostic factor after acute ischemic stroke but is not known whether glucose is associated with the effects of endovascular thrombectomy (EVT) in patients with large-vessel stroke. In a pooled-data meta-analysis, we analyzed whether serum glucose is a treatment modifier of the efficacy of EVT in acute stroke. Methods— Seven randomized trials compared EVT with standard care between 2010 and 2017 (HERMES Collaboration [highly effective reperfusion using multiple endovascular devices]). One thousand seven hundred and sixty-four patients with large-vessel stroke were allocated to EVT (n=871) or standard care (n=893). Measurements included blood glucose on admission and functional outcome (modified Rankin Scale range, 0–6; lower scores indicating less disability) at 3 months. The primary analysis evaluated whether glucose modified the effect of EVT over standard care on functional outcome, using ordinal logistic regression to test the interaction between treatment and glucose level. Results— Median (interquartile range) serum glucose on admission was 120 (104–140) mg/dL (6.6 mmol/L [5.7–7.7] mmol/L). EVT was better than standard care in the overall pooled-data analysis adjusted common odds ratio (acOR), 2.00 (95% CI, 1.69–2.38); however, lower glucose levels were associated with greater effects of EVT over standard care. The interaction was nonlinear such that significant interactions were found in subgroups of patients split at glucose < or >90 mg/dL (5.0 mmol/L; P =0.019 for interaction; acOR, 3.81; 95% CI, 1.73–8.41 for patients < 90 mg/dL versus 1.83; 95% CI, 1.53–2.19 for patients >90 mg/dL), and glucose < or >100 mg/dL (5.5 mmol/L; P =0.004 for interaction; acOR, 3.17; 95% CI, 2.04–4.93 versus acOR, 1.72; 95% CI, 1.42–2.08) but not between subgroups above these levels of glucose. Conclusions— EVT improved stroke outcomes compared with standard treatment regardless of glucose levels, but the treatment effects were larger at lower glucose levels, with significant interaction effects persisting up to 90 to 100 mg/dL (5.0–5.5 mmol/L). Whether tight control of glucose improves the efficacy of EVT after large-vessel stroke warrants appropriate testing.

Background and Purpose— Time to reperfusion is fundamental in reducing morbidity and mortality in acute stroke. We aimed to demonstrate that direct transfer to angio-suite (DTAS) of patients with suspected large vessel occlusion stroke improves workflow times and outcomes. Methods— A case-control matched study of the first 79 DTAS patients with confirmed large vessel occlusion (cases) and 145 no-DTAS patients (controls). DTAS protocol included a cone beam computed tomography in the angio-suite to rule out intracerebral hemorrhage for those patients with no prior neuroimaging in a referring center. Cases and controls were matched by location of vessel occlusion, age, baseline National Institutes of Health Stroke Scale (NIHSS) score and time from symptoms onset to Comprehensive Stroke Center arrival. Dramatic clinical improvement was defined as a decrease in NIHSS score of >10 points or final NIHSS score of ≤2. Favorable outcome was defined as modified Rankin Scale score of ≤2 at 90 days. Results— During an 18 months period a total of 97 patients were directly transferred to the angio-suite after admission: 11 (11.6%) showed an intracerebral hemorrhage on cone beam computed tomography, 7 (7.2%) did not have a large vessel occlusion on initial angiogram, and 79 (76.3%) had a large vessel occlusion and received endovascular treatment (cases). There were no differences in age, baseline NIHSS score, level of occlusion and time from onset-to-door between cases and controls. The median door-to-groin time (16 [12–20] versus 70 [45–105] minutes; P P P =0.01), higher rate of dramatic improvement (50.6% Vs. 31.7%; P =0.04), and higher rate of favorable clinical outcome at 90 days (41% versus 28%; P =0.05). A logistic regression model adjusting for all matching variables showed that DTAS protocol was independently associated with 3 months favorable outcome (odds ratio, 2.5; 95% CI, 1.2–5.3; P =0.01). Conclusions— DTAS is an effective strategy to reduce workflow time which may significantly increase the odds of achieving a favorable outcome.

Introduction: Different studies have pointed that CT perfusion(CTP) could overestimate ischemic core in early time window. We aim to evaluate the influence of time and collateral status on ischemic core overestimation. Methods: Retrospective single-center study including patients with anterior circulation large-vessel stroke that achieved reperfusion after endovascular treatment. Ischemic core and collateral status were automatically estimated on baseline CTP using available software. CTP-derived core was considered as tissue with a relative reduction of cerebral blood flow 6 seconds with Tmax>10 seconds, HIR). Final infarct was measured on 24-48 hours non-contrast CT. Ischemic core overestimation was considered when CTP-derived core was larger than final infarct. Results: Four-hundred and seven patients were included in the analysis. Median CTP-derived core and final infarct were 7mL(IQR 0-27) and 20mL(IQR 5-55), respectively. Median HIR was 0.46(IQR 0.23-0.59). 83 patients(21%) presented ischemic core overestimation(median overestimation, 12mL(IQR 5-41)). Multivariable logistic regression analysis adjusted by CTP-derived core and confounding variables showed that poor collateral status (per 0.1 HIR increase, adjusted odds ratio(aOR) 1.41, 95% confidence interval(CI)1.20-1.65) and earlier onset to imaging time(per 60 minutes earlier, aOR 1.14, CI1.04-1.25) were independently associated with ischemic core overestimation. No significant association was found with imaging to reperfusion time(per 30 minutes earlier, aOR 1.17 CI0.96-1.44). Poor collateral status influence on ischemic core overestimation differed according to onset to imaging time, with a stronger size of effect on early imaging patients(pinteraction Conclusion: In patients with large vessel stroke that achieve reperfusion after endovascular therapy, poor collateral status might induce higher rates of ischemic core overestimation on CTP, especially in patients in earlier window time. CTP reflects a hemodynamic state rather than tissue fate; collateral status and onset to imaging time are important factors to estimate ischemic core on CTP.

Methods: We analyzed data from 190 patients in a prospective unicentric study. Thrombi obtained in emergent endovascular treatment ( EVT) were analyzed by MFC order to calculate the percentage of granulocytes , monocytes and lymphocytes, over total leukocyte population as well as monocyte-to-lymphocyte ratio ( MLR) Clinical and interventional parameters were recorded for each patient. Stroke subtypes were defined by the Trial of ORG 10172 in Acute Stroke Treatment classification. We tested MFC predictors of high risk cardioembolic strokes (HR CE) in patients with undetermined stroke etiology . MFC predictor was obtained by comparison of clots due to Large Arterial Atherosclerosis compared with clots due to HR CE. Results: Among 190 clots retrieved, 163 cases were properly analized. 91 cases with known stroke etiology after EVT and 72 cases of Undetermined stroke. In a demographic (age, gender) and EVT matched (time, tpa, number of passes) case -control study of 56 patients: HR CE strokes (28 cases) and LAA strokes (28 cases), the proportion of monocytes ( OR 1.06 , 95% CI 1.01- 1.11) and MLR ( OR 1.83 , 95% CI 1.12- 2.98) independently predicted HR CE detection. A cut-off point of 1.77% in a receiver operating characteristic curve predicted cardiomebolic etiology with sensitivity of 71% and specificity of 82%. Among Undetermined Strokes (n=72) the percentage of HR CE detection was higher in patients with high MLR (n=40 ; 74%) compared with low MLR (n=6; 33%) ( p< 0.001). Patients with high MLR were older than low MLR cases, although MLR > 1.77 independently predicted HR CE detection among Undetermined strokes (OR, 4.50 ,95% CI 1.35-15.04) in a multivariate model adjusted for age. Conclusion: Measurement of monocyte to lymphocyte ratio in clots by multiparametric flow cytometry detected patients at high risk of hidden cardioembolic origin among undetermined stroke population.

Introduction: External recorders allow for low-cost, non-invasive 1 to 4 weeks monitoring. However, the first 3 months of monitoring duration are the most effective to detect atrial fibrillation (AF). We show the results of the Thunder registry of patients monitored to detect AF during 90 days from the stroke. Methods: A prospective observational study was conducted with consecutive inclusion of patients with cryptogenic stroke after work up (neuroimaging, echocardiography and 24-hour cardiac monitoring) in 5 Comprenhensive Stroke Centers. Patients were continuously monitored for 90 days with a wearable Holter (Nuubo®) after the first 24 hours of the stroke onset. We analyzed the percentage of AF detection in each period (percentage of AF among those monitored), the quality of the monitoring (monitoring time), the percentage of AF by intention to monitor (detection of AF among patient included). Demographic, clinical and echocardiographic predictors of AF detection beyond one week of cardiac monitoring were assessed. Results: A total of 254 patients were included. The cumulative incidence of AF detection at 90 days was 34.84%. The monitoring time was similar among the 3 months (30 days: 544.9 hours Vs 60 days: 505.9 hours Vs 90 days: 591.25 hours) (p=0.512). The number of patients who abandoned monitoring was 7% (18/254). The cumulative percentage of intention to detect AF was 30.88% (Figure). Patients who completed monitoring beyond 30 days had higher score on the NIHSS basal scale (NIHSS 9 IQR 2-17) VS (NIHSS 3 IQR 1-9) (p=0.024). Patients with left atrial volume greater than 28.5ml/m2 had higher risk of cumulative incidence of AF according to the Kaplan Meyer curve beyond the first week of monitoring OR 2.72 (Log-rank (Mantel-Cox test) (p Conclusions: In conclusion, intensive 90-day- Holter monitoring with textile Holter was feasible and detected high percentage of AF. Enlarged left atrial volume predicted AF beyond the first week of monitoring.

Producción Científica, Cerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer’s disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation., Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - (grant PI13/00364, PI16/00471, PI14/01134 and PI17/00275), Instituto de Salud Carlos III - (grant FI17/00031), Instituto de Salud Carlos III, Programa Miguel Servet - (grant CPII17/00010), Instituto de Salud Carlos III - (project RD16/0019/0021), Generalitat de Catalunya - (Grupo 2017-SGR-1149)

Background and Purpose: We aim to evaluate if good collateral flow (CF) modifies endovascular therapy (EVT) efficacy on large-vessel stroke. To do that, we used final degree of reperfusion and number of device-passes performed, factors previously associated with better functional outcome, as main outcome measures. Methods: Single-center retrospective study including consecutive stroke patients receiving EVT for anterior circulation large-vessel stroke. CF degree was assessed on CT angiography before EVT using a previously validated 4-grade score. Final degree of reperfusion, using modified Thrombolysis in Cerebral Ischemia (mTICI), and number of device-passes performed were prospectively collected. Multivariable analysis was performed to evaluate the influence of collateral flow degree on final degree of reperfusion and number of device-passes performed. Results: Six hundred twenty-six patients were included in the study; 369 patients (59%) presented good collateral flow on CT angiography. Five hundred twenty-two patients (84%) achieved successful reperfusion (mTICI 2B-3) after EVT, 304 (48%) of them with a final mTICI 2C-3. Median number of device-passes was 2 (interquartile range, 1–3). Good CF was independently associated with better final degree of reperfusion (shift analysis for mTICI0-2A/2B/2C-3%, poor CF 19/38/43 versus good CF 15/32/53, adjusted odds ratio, 1.51 [95% CI, 1.08–2.11]). Poor CF was independently associated with higher number of device-passes performed to achieve successful reperfusion (mTICI2B-3; shift analysis for 1/2/3/4+ device-passes, adjusted odds ratio, 1.59, [95% CI, 1.09–2.31]) and complete reperfusion (mTICI2C-3; shift analysis for 1/2/3/4+ device-passes, adjusted odds ratio, 1.70 [95% CI, 1.04–2.90]). Conclusions: Patients with good CF treated with EVT experience higher rates of successful reperfusion with lower number of device-passes. CF may facilitate thrombus retrieval and prevent distal embolization of clot fragments, improving device-passes efficacy.

The aim of the study was to find markers of high-risk cardioembolic etiology (HRCE) in patients with cryptogenic strokes (CS) through the analysis of intracranial clot by flow cytometry (FC). A prospective single-center study was designed including patients with large vessel occlusion strokes. The percentage of granulocytes, monocytes, lymphocytes, and monocyte-to-lymphocyte ratio (MLr) were analyzed in clots extracted after endovascular treatment (EVT) and in peripheral blood. Large arterial atherosclerosis (LAA) strokes and high-risk cardioembolic (HRCE) strokes were matched by demographics and acute reperfusion treatment data to obtain FC predictors for HRCE. Multilevel decision tree with boosting random forest classifiers was performed with each feature importance for HRCE diagnosis among CS. We tested the validity of the best FC predictor in a cohort of CS that underwent extensive diagnostic workup. Among 211 patients, 178 cases underwent per-protocol workup. The percentage of monocytes (OR 1.06, 95% CI 1.01-1.11) and MLr (OR 1.83, 95% CI 1.12-2.98) independently predicted HRCE diagnosis when LAA clots (n = 28) were matched with HRCE clots (n = 28). Among CS (n = 82), MLr was the feature with the highest weighted importance in the multilevel decision tree as a predictor for HRCE. MLr cutoff point of 1.59 yield sensitivity of 91.23%, specificity of 44%, positive predictive value of 78.79%, and negative predictive value of 68.75 for HRCE diagnosis among CS. MLr >= 1.6 in clot analysis predicted HRCE diagnosis (OR, 6.63, 95% CI 1.85-23.71) in a multivariate model adjusted for age. Clot analysis by FC revealed high levels of monocyte-to-lymphocyte ratio as an independent marker of cardioembolic etiology in cryptogenic strokes.

Resumen Objetivo Proporcionar un conjunto de recomendaciones actualizadas y basadas en la evidencia disponible para el manejo del ictus agudo. Nuestro objetivo es proporcionar una base para el desarrollo de los protocolos internos de cada centro, sirviendo de referencia para los cuidados de enfermeria. Metodos Revision de evidencias disponibles sobre los cuidados del ictus agudo. Se han consultado las guias nacionales e internacionales mas recientes. Los niveles de evidencia y grados de recomendacion se han basado en la clasificacion del Centro de Medicina Basada en la Evidencia de Oxford. Resultados Se describen la atencion y los cuidados del ictus agudo en la fase prehospitalaria, el funcionamiento de codigo ictus, la atencion por el equipo de ictus a la llegada al hospital, los tratamientos de reperfusion y sus limitaciones, el ingreso en la Unidad de Ictus, los cuidados de enfermeria en la Unidad de Ictus y el alta hospitalaria. Conclusiones Estas pautas proporcionan recomendaciones generales basadas en la evidencia actualmente disponible para guiar a los profesionales que atienden a pacientes con ictus agudo. En algunos casos, sin embargo, existen datos limitados demostrando la necesidad de continuar investigando sobre el manejo del ictus agudo.

Background An increased rate of thrombotic events has been associated to Coronavirus Disease 19 (COVID-19) with a variable rate of acute stroke. Our aim is to uncover the rate of acute stroke in COVID-19 patients and identify those cases in which a possible causative relationship could exist. Methods We performed a single-center analysis of a prospective mandatory database. We studied all patients with confirmed COVID-19 and stroke diagnoses from March 2nd to April 30th. Demographic, clinical, and imaging data were prospectively collected. Final diagnosis was determined after full diagnostic work-up unless impossible due to death. Results Of 2050 patients with confirmed SARS-CoV-2 infection, 21 (1.02%) presented an acute ischemic stroke 21 and 4 (0.2%) suffered an intracranial hemorrhage. After the diagnostic work-up, in 60.0% ischemic and all hemorrhagic strokes patients an etiology non-related with COVID-19 was identified. Only in 6 patients the stroke cause was considered possibly related to COVID-19, all of them required mechanical ventilation before stroke onset. Ten patients underwent endovascular treatment; compared with patients who underwent EVT in the same period, COVID-19 was an independent predictor of in-hospital mortality (50% versus 15%; Odds Ratio, 6.67; 95% CI, 1.1-40.4; p 0.04). Conclusions The presence of acute stroke in patients with COVID-19 was below 2% and most of them previously presented established stroke risk factors. Without other potential cause, stroke was an uncommon complication and exclusive of patients with a severe pulmonary injury. The presence of COVID-19 in patients who underwent EVT was an independent predictor of in-hospital mortality.

Introduction Direct transfer to angiosuite (DTAS) has consistently shown to be effective and safe shortening in-hospital workflows and encouraging long-term outcome benefits. In order to generalize DTAS an organizational and manpower effort is necessary. We aim to perform a cost-effective analysis of the implementation of a new angiography suite primarily dedicated to DTAS of stroke patients that will allow generalization of this pathway. Material and Methods 61 patients who underwent endovascular treatment (EVT) following DTAS were matched for baseline variables to 117 patients who underwent conventional imaging protocol before EVT. An economic model based on current data was developed to assess the short and long term clinical and economic implications. The DTAS development scenario estimates a gradual 20% increase of DTAS rate for 4 years followed by a stable 80% rate of DTAS. Initial investment and additional organizational costs were included: 4M €. A cost-effective study compared the DTAS development scenario (SC1) to a scenario with no organizational changes (SC2) over 10 years. Results The 10 year model included 1775 EVT patients in each scenario: SC1 68% DTAS Vs SC2 0% DTAS. SC1 would be associated with better functional independence rates (mRS 0–2: 45.8% versus 40.2% p=0.04) and a quality-adjusted life-years gain of 0.12 per patient. Despite the additional investment, SC1 development was associated with an estimated 15.1% reduction (26.25M €) of total costs (173.749M €). Cost saving was mainly due to long-term associated costs related with patient disability (€ 26.4 million). Conclusions Our economic model predicts that the development of a DTAS program is cost effective. Disclosures M. Requena: None. V. Seguel: None. M. Olive-Gadea: None. A. Garcia-Tornel: None. A. Vilaseca: None. N. Rodriguez-Villatoro: None. M. Deck: None. J. Juega: None. S. Boned: None. M. Muchada: None. C. Pinana: None. J. Pagola: None. D. Rodriguez-Luna: None. D. Hernandez: None. M. Rubiera: None. C. Molina: None. A. Tomasello: None. M. Ribo: 2; C; Medtronic, Stryker, Johnson and Johnson, Anaconda Biomed, Apta Targets.

Background and Purpose— Direct transfer to angiography-suite (DTAS) protocol is a promising measure to improve onset to recanalization time in patients who undergo endovascular treatment. The magnitude of the improvement of good outcome rates in function of time depends of several factors. We aim to analyze the benefit of DTAS according to time from symptom onset. Methods— Retrospective case-control study of 174 consecutive DTAS cases matched with 175 patients initially transferred to computed tomography (directly transferred to computed tomography) from February 2016 to June 2019. To obtain comparable groups on admission, cases and controls were matched by occlusion location, age (±2 years), baseline National Institutes of Health Stroke Scale score (±2 points), and time from symptoms onset to hospital arrival (±30 minutes). We analyzed the rate of good functional outcome at 3 months (modified Rankin Scale score, 0–2) and safety variables stratified in less or more than 3 hours from onset to arrive. Results— There were no significant differences regarding age, sex, or baseline National Institutes of Health Stroke Scale score. Median door-to-groin time was shorter in the DTAS patients (16 [3–21] minutes versus 70 [41.5–98.5]; P P =0.01) and a lower rate of symptomatic hemorrhagic transformation (4.6% versus 10.9%, P P =0.01). Better outcome in DTAS was observed in patients admitted in the 0 to 3 hours form onset window (n=156, odds ratio 2.63 [95% CI, 1.31–5.28]; P P =0.2). Conclusions— DTAS seems a feasible and safe strategy to improve functional outcome in patients who undergo endovascular treatment mainly within 3 hours from symptoms onset.

Background and Purpose— First pass (FP) recanalization has been shown to be a predictor of favorable outcome in endovascular treatment of stroke. The reasons why FP recanalization leads to better outcome as compared with multiple passes (MP) are unknown. We aim to investigate the recanalization pattern and its relationship with outcome. Methods— Six hundred nine consecutive patients underwent endovascular treatment. Recanalization was defined as modified Thrombolysis in Cerebral Infarction score 2B-3. Favorable outcome was defined as modified Rankin Scale score of 0 to 2 at 90 days. Sudden recanalization (SR) was considered when modified Thrombolysis in Cerebral Infarction score varied from 0-1 to 2B-3 in a single pass. Progressive recanalization (PR) was considered if modified Thrombolysis in Cerebral Infarction score 2A was achieved at an interim pass before achieving recanalization. Patients were also categorized as recanalizers at FP, MP, or nonrecanalizers. Results— Five hundred nine (83.9%) patients achieved recanalization. SR was achieved in 378 (62.1%) patients; 280 (46%) were FP-SR, and 98 (16.1%) were MP-SR. MP-PR was achieved in 131 (21.5%) patients. Rates of favorable outcome were similar between patients with FP-SR (57.5%) and MP-SR (57.1%; odds ratio [OR], 0.9 [CI, 0.53–1.54]; P =0.7) but lower in MP-PR (29.8%; OR, 3.33 [CI, 1.71–5.63]; P P P P P P P =0.937). Conclusions— SR strongly predicts favorable outcome in patients undergoing endovascular treatment, even after previous unsuccessful attempts. PR may reflect clot fragmentation and embolization due to more friable composition, leading to worse outcomes. Prospective studies with independent assessment of recanalization pattern should validate these results.

Introduction: Systemic blood pressure (BP) should be strictly monitored and adjusted during the initial stages of stroke. Due to the impairment of cerebral autoregulation, cerebral blood flow is directly affected by systemic BP and some degree of permissive hypertension might be beneficial prior to reperfusion treatments to ensure an adequate perfusion in the ischemic tissue. However, after generalization of endovascular treatment (EVT) the rate of successful recanalization has skyrocketed and it is not well established if, once achieved, BP control should be stricter given its potential risks. We aim to explore the relation between BP and outcome among patients who underwent EVT. Methods: This is a retrospective study of a prospectively acquired unicentric database that includes patients who underwent EVT with successful recanalization measured by a mTICI ≥2b. Hourly measuring of systolic and diastolic BP was conducted during the first 24 hours post-procedure. BP variation was measured using standard deviation (SD) and range. We explored the effects of BP on functional outcome at 3 months and safety variables. Results: The study included 351 subjects with a mean age of 72.7+/-13.1 and 51.6% were men. The 3-months mRS was ≤2 in 50.4% of patients, 66 subjects (19.2%) presented hemorrhagic transformation and 67 (19.1%) were dead in the 3-months follow-up period. Both systolic BP SD (15.6+/-9.9 vs. 12.9+/-4.3; p2). Subjects with hemorrhagic transformation presented higher range of DBP (35.7+/-12.4 vs. 32.0+/-11.9; p=0.03) and SBP (56.8+/-17.0 vs. 51.4+/-18.1; p=0.03) and higher diastolic DBP SD (9.3+/-4.1 vs. 8.2+/-2.7; p Conclusions: Major fluctuations in systolic and diastolic BP predict increased risk of hemorrhagic complications and poor functional outcome. Minimizing BP fluctuations may improve outcome of EVT patients after recanalization.

Background: CTA spot sign is a predictor of intracerebral hemorrhage (ICH) expansion. This sign can fluctuate in appearance, volume, and timing. Multiphase CTA (mCTA) can identify spot sign through 3 time-resolved images. We sought to identify a novel predictor of follow up total hematoma expansion using mCTA. Methods: This cohort study included patients with ICH between 2012-2019. Quantomo software was used to measure total hematoma volume (ml) from baseline CT & follow-up CT/MRI blinded to spot sign in 3 mCTA phases. Spot sign expansion was calculated by subtracting 1 st phase spot sign volume from 2 nd phase spot sign volume measured in microliters. Results: 199 patients [63% male, mean age 69 years, median NIHSS 11, IQR 6-20] were included. Median baseline ICH volume was 16.1 ml (IQR 5-29.9 ml). Amongst all three mCTA phases, spot sign was best detected on the 2nd phase (23% vs 17.5% 1 st phase vs 22% 3 rd phase). In multivariable regression, spot sign expansion was significantly associated with follow up total hematoma expansion (OR: 1.03 per microliter of spot sign expansion, p=0.01). Figure 1 shows the predicted total hematoma expansion by spot sign expansion. mCTA spot sign had a higher sensitivity for predicting total hematoma volume expansion than single-phase CTA (reported in meta-analysis of 14 studies), 86% vs 53%, respectively, while both having similar specificity, 87% vs 88%, respectively. Conclusion: Spot sign expansion on mCTA is a novel predictor of total hematoma expansion and could be used to select patients for immediate therapeutic intervention in future clinical trials. Using mCTA improves sensitivity while preserving specificity over single-phase CTA.

Background and Purpose: Extracranial internal carotid artery (ICA) lesion in the setting of tandem occlusions is a therapeutic challenge, and hemorrhagic transformation (HT) is one of the leading causes of poor clinical outcome. We aimed to determine determinants of HT for tandem occlusions undergoing emergent extracranial ICA stenting during endovascular treatment (EVT). Methods: We performed a prospective, observational cohort study of consecutive patients with non-cardioembolic ischemic stroke due to tandem occlusion who underwent EVT with extracranial ICA stent placement during the procedure from April 2013 to June 2019 in a single stroke center. We compared clinical (vascular risk factors, previous antiplatelet treatment, and IV rtPA), radiological (ASPECTS at admission and in-stent thrombosis at 24 hours) and serological (platelet count, fibrinogen, total cholesterol, HDL-cholesterol, and LDL-cholesterol) parameters according to the presence of HT in 24 hours CT-scan. Results: One-hundred and eight patients were included: 78.7% were men, mean age 68.5±14.3 years, median time from symptoms onset to treatment was 220 (150-337.5) minutes, median ASPECTS at admission was 9 (8-10). Eighty-six (79.6%) patients presented an extracranial ICA occlusion, and 22 (20.4%) a high-grade (>50%) stenosis. In 88 (81.5%) patients the etiology of extracranial ICA lesion was ateroma, and in 20 (18.5%) was a dissection. Intravenous rtPA was administered in 47 (43.5%) patients. Successful recanalization (mTICI ≥2b) was achieved in 83 (76.9%) patients, and extracranial ICA recanalization in 108 (100%) patients. Type 2 diabetes (OR 1.5, 95% CI 1.1-3.5), higher fibrinogen levels (OR 4.6, 95% CI 1.6-12.9), and ASPECTS Conclusions: Patients with a non-cardioembolic ischemic stroke due to tandem occlusion who present type 2 diabetes, higher fibrinogen levels, or ASPECTS

Introduction: First pass recanalization (FPR) is known to be a strong predictor of good outcome in endovascular treatment (EVT) of stroke. The reasons why FPR leads to better outcome than if achieved in multiple-passes (MP) are unknown. We aim to investigate the recanalization pattern and its relation with good outcome. Methods: 609 consecutive patients underwent EVT in the anterior circulation at a single stroke center. Demographic and imaging characteristics, number of passes and recanalization pattern were recorded. Complete recanalization was defined as mTICI2b-3 at the end of EVT. Good functional outcome was defined as modified Rankin scale (mRs) 0-2 at 90 days. Sudden recanalization(SR) was considered when mTICI score varied from 0-1 to 2B-3 in a single pass. Progressive recanalization (PR) was considered if mTICI 2a was achieved at an interim pass before achieving complete recanalization. Patients were categorized as recanalizers at first-pass (FP) and multiple-passes (MP) or non-recanalizers (NR). 70 (10.3%) patients in MP group were excluded due to missing procedural data. Results: 509 (83.9%) patients achieved complete recanalization. SR was achieved in 378 (62.1%) patients; 280 (46%) were FP-SR and 98 (16.1%) were MP-SR. MP-PR was achieved in 131 (21.5%) patients. Rates of good functional outcome depending on recanalization pattern were: FP-SR 57.5%, MP-SR 57.1% (FP-SR vs MP-SR, OR 0.9 CI 0.53-1.54, p=0.7), MP-PR 29.8% (MP-SR vs MP-PR, OR 3.06 CI 1.66-5.62, p Conclusions: Sudden recanalization is a strong predictor of good functional outcome in patients undergoing EVT, even after previous unsuccessful attempts. Progressive recanalization may reflect clot fragmentation and embolization due to more friable composition, leading to worse outcomes. Benefits of first pass effect are driven by sudden recanalization.

Introduction: Perfusion imaging has emerged as an imaging tool to select patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) for endovascular treatment (EVT). We aim to compare an automated method to assess the infarct ischemic core (IC) in Non-Contrast Computed Tomography (NCCT) with Computed Tomography Perfusion (CTP) imaging and its ability to predict functional outcome and final infarct volume (FIV). Methods: 494 patients with anterior circulation stroke treated with EVT were included. Volumetric assessment of IC in NCCT (eA-IC) was calculated using eASPECTS™ (Brainomix, Oxford). CTP was processed using availaible software considering CTP-IC as volume of Cerebral Blood Flow (CBF) Results: Median eA-IC and CTP-IC were 16 (IQR 7-31) and 8 (IQR 0-28), respectively. 419 patients (85%) achieved complete recanalization, and their median FIV was 17.5cc (IQR 5-52). Good functional outcome was achieved in 230 patients (47%). EA-IC and CTP-IC had moderate correlation between them (r=0.52, p40cc, OR 1.5, IC1.3-1.8, p Conclusion: Automated volumetric assessment of infarct core in NCCT has similar performance predicting prognosis and final infarct volume than CTP. Prospective studies should evaluate a NCCT-core / vessel occlusion penumbra missmatch as an alternative method to select patients for EVT.

Direct transfer to angio suite (DTAS) protocol is a promising measure to improve onset to recanalization time in patients who undergo endovascular treatment. The association of different time windows with prognosis in this population is influenced by several factors. We aim to analyze the influence of DTAS in clinical and functional outcome depending on time from symptom onset to treatment. Methods: Retrospective case-control study of 174 consecutive DTAS cases matched with 175 patients initially transferred to CT (DTCT) from February 2016 to April 2019. To obtain comparable groups on admission, cases and controls were matched by occlusion location, age (±2 years), baseline NIHSS score (±2 points) and time from symptoms onset to hospital arrival (±30 minutes). We analyzed the rate of good functional outcome at 3 months (mRS 0-2) and safety variables stratified in less or more than 3 hours from onset to arrive. Results: There were no significant differences regarding age, gender or baseline NIHSS score (table 1). Median door-to-groin time was shorter in the DTAS patients (16 (13-21) minutes Vs 70 (41.5-98.5); p Conclusion: DTAS seems a feasible and safe strategy to improve functional outcome in patients who undergo endovascular treatment mainly within 3 hours from symptoms onset.

On CT perfusion (CTP), cerebral blood flow < 30% than the contralateral hemisphere (CBF Methods: Retrospective analysis of a prospective database of acute ischemic strokes who underwent CTP on admission and immediately after endovascular thrombectomy (EVT). CC was graded on CT angiography (CTA) by the modified Tan scale (good CC: 2-3 grades). Complete recanalization was defined by modified Thrombolysis in Cerebral Ischemia ≥ 2B. Final infarct volume (FIV) was semi-automatically measured on 48-72h CT; ghost core was defined as: admission CBF 10cc. Results: We included 494 patients; median time from onset to CT: 137 min (IQR 68-238). Median CBF10cc)). Even in recanalized patients, baseline CBF Conclusion: CBF

We aim to define a target population of stroke patients treated with EVT, in whom a potential neuroprotective (NP) drug has highest chances to show clinical and radiological positive effects. Methods: we studied stroke patients treated with EVT. CBF Results: We included 211 patients, mean FIV was 39(±58)cc and median dNIHSS 6(1-15). FIV strongly correlated to dNIHSS (rs=0.74; p Conclusion: One in 4 patients will develop minimal FIV, including these patients in NP trials may dilute a treatment effect and reduce odds of positive results. In large FIV patients, mild relative clinical impacts may become relevant due to substantial absolute FIV reductions. Admission CTP may help sorting patients according to expected drug effect profile.

Introduction Spontaneous blood pressure drop within the first 24 h has been reported following arterial recanalisation in ischaemic stroke patients. We aimed to assess if spontaneous blood pressure drop within the first hour after mechanical thrombectomy is a marker of early neurological recovery. Patients and methods Retrospective observational single-centre study including ischaemic stroke patients treated with mechanical thrombectomy. Blood pressure parameters from admission, mechanical thrombectomy start, mechanical thrombectomy end and hourly within 24 h after mechanical thrombectomy were reviewed. Primary outcome was early dramatic neurological recovery (8-point-reduction in NIHSS or NIHSS ≤ 2 at 24 h). Secondary outcome was functional independence at 90 days (mRankin 0–2). Results We included 458 patients in our analysis. Two-hundred (43.7%) patients achieved dramatic neurological recovery following mechanical thrombectomy. One hour after mechanical thrombectomy end, median systolic blood pressure was significantly different between outcome groups (129 vs. 138 mmHg, p = 0.005) and a higher drop in median systolic blood pressure was seen in the dramatic neurological recovery group (15 vs. 9 mmHg). Optimal cut-off for predicting dramatic neurological recovery was a systolic blood pressure drop of 10.5 mmHg (sensitivity 0.54, specificity 0.55, AUC 0.55). On multivariate analysis, spontaneous systolic blood pressure drop was associated with higher odds of achieving dramatic neurological recovery (OR for 10 mmHg blood pressure drop 1.14, 95% CI 1.01–1.29, p = 0.04). No significative association between any blood pressure parameter drop and functional independence at 90 days was found. Discussion We hypothesised that spontaneous systolic blood pressure drop is a marker of successful reperfusion and, therefore, a marker of improvement of cerebral autoregulation due to the reduced final ischaemic core. Conclusion Spontaneous systolic blood pressure drop after mechanical thrombectomy is an early predictor of dramatic neurological recovery.

Background and Purpose— The intracerebral hemorrhage (ICH) score is the most commonly used grading scale for stratifying functional outcome in patients with acute ICH. We sought to determine whether a combination of the ICH score and the computed tomographic angiography spot sign may improve outcome prediction in the cohort of a prospective multicenter hemorrhage trial. Methods— Prospectively collected data from 241 patients from the observational PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign) were analyzed. Functional outcome at 3 months was dichotomized using the modified Rankin Scale (0–3 versus 4–6). Performance of (1) the ICH score and (2) the spot sign ICH score—a scoring scale combining ICH score and spot sign number—was tested. Results— Multivariable analysis demonstrated that ICH score (odds ratio, 3.2; 95% confidence interval, 2.2–4.8) and spot sign number (n=1: odds ratio, 2.7; 95% confidence interval, 1.1–7.4; n>1: odds ratio, 3.8; 95% confidence interval, 1.2–17.1) were independently predictive of functional outcome at 3 months with similar odds ratios. Prediction of functional outcome was not significantly different using the spot sign ICH score compared with the ICH score alone (spot sign ICH score area under curve versus ICH score area under curve: P =0.14). Conclusions— In the PREDICT cohort, a prognostic score adding the computed tomographic angiography–based spot sign to the established ICH score did not improve functional outcome prediction compared with the ICH score.

We describe the feasibility of monitoring with a Textile Wearable Holter (TWH) in patients included in Crypto AF registry.We monitored cryptogenic stroke patients from stroke onset (3days) continuously during 28days. We employed a TWH composed by a garment and a recorder. We compared two garments (Lead and Vest) to assess rate of undiagnosed Atrial Fibrillation (AF) detection, monitoring compliance, comfortability (1 to 5 points), skin lesions, and time analyzed. We describe the timing of AF detection in three periods (0-3, 4-15 and 16-28days).The rate of undiagnosed AF detection with TWH was 21.9% (32 out of 146 patients who completed the monitoring). Global time compliance was 90% of the time expected (583/644h). The level of comfortability was 4 points (IQR 3-5). We detected reversible skin lesions in 5.47% (8/146). The comfortability was similar but time compliance (in hours) was longer in Vest group 591 (IQR [521-639]) vs. Lead 566 (IQR [397-620]) (p=0.025). Also, time analyzed was more prolonged in Vest group 497 (IQR [419-557]) vs. Lead (336h (IQR [140-520]) (p=0.001)). The incidence of AF increases from 5.6% (at 3days) to 17.5% (at 15th day) and up to 20.9% (at 28th day). The percentage of AF episodes detected only in each period was 12.5% (0-3days); 21.7% (4-15days) and 19% (16-28days).28days Holter monitoring from the acute phase of the stroke was feasible with TWH. Following our protocol, only five patients were needed to screen to detected one case of AF.