Derivation and validation of three intracerebral hemorrhage expansion scores using different CT modalities.

OBJECTIVES: To derivate and validate three scores for the prediction of intracerebral hemorrhage (ICH) expansion depending on the use of non-contrast CT (NCCT), single-phase CTA, or multiphase CTA markers of hematoma expansion, and to evaluate the added value of single-phase and multiphase CTA over NCCT. METHODS: After prospectively deriving NCCT, single-phase CTA, and multiphase CTA hematoma expansion scores in 156 patients with ICH < 6 h, we validated them in 120 different patients. Discrimination and calibration of the three scores was assessed. Primary outcome was substantial hematoma expansion > 6 mL or > 33% at 24 h. RESULTS: The evaluation of single-phase and multiphase CTA markers gave a steadily increase in discrimination for substantial hematoma expansion over NCCT markers. The C-index (95% confidence interval) in derivation and validation cohorts was 0.69 (0.58-0.80) and 0.59 (0.46-0.72) for NCCT score, significantly lower than 0.75 ([0.64-0.87], p = 0.038) and 0.72 ([0.59-0.84], p = 0.016) for single-phase CTA score, and than 0.79 ([0.68-0.89], p = 0.033) and 0.73 ([0.62-0.85], p = 0.031) for multiphase CTA score, respectively. The three scores showed good calibration in both derivation and validation cohorts: NCCT (χ2 statistic 0.389, p = 0.533; and χ2 statistic 0.352, p = 0.553), single-phase CTA (χ2 statistic 2.052, p = 0.359; and χ2 statistic 2.230, p = 0.328), and multiphase CTA (χ2 statistic 0.559, p = 0.455; and χ2 statistic 0.020, p = 0.887) scores, respectively. CONCLUSION: This study shows the added prognostic value of more advanced CT modalities in acute ICH evaluation. NCCT, single-phase CTA, and multiphase CTA scores may help to refine the selection of patients at risk of expansion in different decision-making scenarios. KEY POINTS: • This study shows the added prognostic value of more advanced CT modalities in acute intracerebral hemorrhage evaluation. • The evaluation of single-phase and multiphase CTA markers provides a steadily increase in discrimination for intracerebral hemorrhage expansion over non-contrast CT markers. • Non-contrast CT, single-phase CTA, and multiphase CTA scores may help clinicians and researchers to refine the selection of patients at risk of intracerebral hemorrhage expansion in different decision-making scenarios.

Intracranial Artery Calcifications Profile as a Predictor of Recanalization Failure in Endovascular Stroke Treatment.

BACKGROUND: Acute ischemic stroke with large or medium-vessel occlusion associated with intracranial artery calcification (IAC) is an infrequent phenomenon presumably associated with intracranial atherosclerotic disease. We aimed to characterize IAC and its impact on endovascular treatment outcomes. METHODS: We performed a retrospective cross-sectional study of consecutive patients with stroke treated with thrombectomy from January 2020 to July 2021 in our institution. We described IAC findings (length, density, and location pattern) on baseline noncontrast computed tomography. Patients were divided into 3 groups: IAC related to the occlusion location (symptomatic-IAC group), unrelated to the occlusion (asymptomatic-IAC group), and absence of any IAC (non-IAC group). We analyzed the association between the IAC profile and outcomes using logistic regression models. Intracranial angioplasty and stenting were considered rescue treatments. RESULTS: Of the 393 patients included, 26 (6.6%) patients presented a symptomatic-IAC, 77 (19.6%) patients an asymptomatic-IAC, and in 290 (73.8%) patients no IAC was observed. The rate of failed recanalization (expanded Thrombolysis in Cerebral Infarction 0-2a) before rescue treatment was higher in symptomatic-IAC (65.4%) than in asymptomatic-IAC (15.6%; P<0.001) or non-IAC (13.4%; P<0.001). Rescue procedures were more frequently performed in symptomatic-IAC (26.9%) than in asymptomatic-IAC (1.3%; P<0.001) and non-IAC (4.1%; P<0.001). After adjusting for identifiable clinical and radiological confounders, symptomatic-IAC emerged as an independent predictor of failed recanalization (odds ratio, 11.89 [95% CI, 3.94-35.91]; P<0.001), adoption of rescue procedures (odds ratio, 12.38 [95% CI, 2.22-69.09]; P=0.004), and poor functional outcome (90-day modified Rankin Scale score ≥3; odds ratio, 3.51 [95% CI, 1.02-12.00]; P=0.046). CONCLUSIONS: The presence of IAC related to the occlusion location is associated with worse angiographic and functional outcomes. Therefore, identification of symptomatic-IAC on baseline imaging may guide optimal endovascular treatment strategy, predicting the need for intracranial stenting and angioplasty.

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

INTRODUCTION: 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.

Multiparametric Neuroimaging and Its Association with Non-Contrast Computed Tomography in Late-Window Large Vessel Occlusion Acute Stroke.

INTRODUCTION: Endovascular treatment (EVT) for acute ischemic stroke (AIS) between 6 and 24 h is established as a standard of care among patients selected by multiparametric neuroimaging. We aimed to explore neuroimaging parameters in late-window large vessel occlusion (LVO) patients and its association with non-contrast computed tomography (NCCT) findings. METHODS: We included consecutive AIS patients within 6-24 h from the symptoms onset with LVO. We described multiparametric imaging findings, the rate of patients who fulfilled imaging perfusion criteria according to the DAWN and DEFUSE-3 trials that define the computed tomography perfusion mismatch (CTP-MM) group and its association with NCCT focused on Alberta Stroke Program Early CT Score (ASPECTS). We also analyzed the association between neuroimaging parameters and the clinical outcome determined by the 90-day modified Rankin scale (mRS). RESULTS: We included 206 patients, of them, 176 (85.4%) presented CTP-MM and 184 (89.3%) presented an ASPECTS ≥6 on admission. The rate of CTP-MM was 90.8% in patients with ASPECTS ≥6, compared with 40.9% in those with low ASPECTS. ASPECTS was moderately correlated with ischemic core determined by cerebral blood flow <30% volume (rS = -0.557, p < 0.001). In EVT-treated patients (185, 89.8%), after adjusting for identifiable confounders, the presence of CTP-MM was a predictor of 90-day functional independence (OR: 3.38; 95% CI: 1.01-11.29; p = 0.048). We did not find an association between CTP-MM and 90-day functional disability (ordinal mRS shift, aOR: 1.39; 95% CI: 0.58-3.34; p = 0.459). CONCLUSIONS: A great majority of patients who presented a LVO in the late window fulfilled guidelines imaging criteria to undergo EVT, especially those with high ASPECTS (≥6). Our data suggest that NCCT with CT angiography could be a reasonable approach for AIS treatment selection also in the late window.

Intensive 90-day textile wearable Holter monitoring: an alternative to detect paroxysmal atrial fibrillation in selected patients with cryptogenic stroke.

We aimed to demonstrate the feasibility of 90-day cardiac monitoring with an external Holter device and to find a target population able to benefit from such a technique. Cryptogenic stroke patients were continuously monitored for 90 days with a textile wearable Holter (TWH). Compliance and quality of the monitoring were assessed by the number of hours of ECG stored per month. Mean predictors of pAF, including age, gender, stroke severity, and atrial size (LAVI), were evaluated. One-year follow-up assessed pAF detection outside per protocol monitoring. Out of 224 patients included in 5 stroke centers, 163 patients (72.76%) fulfilled the criteria for the protocol. Median monitoring time was similar among the three months. Per protocol pAF detection reached 35.37% at 90 days. The age (OR 1.095; 95% CI 1.03-1.14) and the LAVI (OR 1.055; 95% CI 1.01-1.09) independently predicted pAF. The cut-off point of 70 years (AUC 0.68) (95% CI 0.60-0.76) predicted pAF with a sensitivity of 75.8% and specificity of 50.5%. The LAVI cut-off point of 28.5 (AUC 0.67) (95% CI 0.56-0.77) had a sensitivity of 63.6% and a specificity of 61.8% to detect pAF. The combination of both markers enhanced the validity of pAF detection sensitivity to 89.6%, with a specificity of 27.59%. These patients had increased risk of pAF during the 90-day monitoring HR 3.23 (χ2 7.15) and beyond 90 days (χ2 5.37). Intensive 90-days TWH monitoring detected a high percentage of pAF. However, a significant number of patients did not complete the monitoring. Patients older than 70 years and with enlarged left atria benefitted more from the protocol.

Workflow Times and Outcomes in Patients Triaged for a Suspected Severe Stroke.

INTRODUCTION: Current recommendations for regional stroke destination suggest that patients with severe acute stroke in non-urban areas should be triaged based on the estimated transport time to a referral thrombectomy-capable center. METHODS: We performed a post hoc analysis to evaluate the association of pre-hospital workflow times with neurological outcomes in patients included in the RACECAT trial. Workflow times evaluated were known or could be estimated before transport allocation. Primary outcome was the shift analysis on the modified Rankin score at 90 days. RESULTS: Among the 1,369 patients included, the median time from onset to emergency medical service (EMS) evaluation, the estimated transport time to a thrombectomy-capable center and local stroke center, and the estimated transfer time between centers were 65 minutes (interquartile ratio [IQR] = 43-138), 61 minutes (IQR = 36-80), 17 minutes (IQR = 9-27), and 62 minutes (IQR = 36-73), respectively. Longer time intervals from stroke onset to EMS evaluation were associated with higher odds of disability at 90 days in the local stroke center group (adjusted common odds ratio (acOR) for each 30-minute increment = 1.03, 95% confidence interval [CI] = 1.01-1.06), with no association in the thrombectomy-capable center group (acOR for each 30-minute increment = 1.01, 95% CI = 0.98-1.01, pinteraction  = 0.021). No significant interaction was found for other pre-hospital workflow times. In patients evaluated by EMS later than 120 minutes after stroke onset, direct transport to a thrombectomy-capable center was associated with better disability outcomes (acOR = 1.49, 95% CI = 1.03-2.17). CONCLUSION: We found a significant heterogeneity in the association between initial transport destination and neurological outcomes according to the elapse of time between the stroke onset and the EMS evaluation (ClinicalTrials.gov: NCT02795962). ANN NEUROL 2022;92:931-942.

Systematic CT perfusion acquisition in acute stroke increases vascular occlusion detection and thrombectomy rates.

BACKGROUND: In 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. METHODS: From 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). RESULTS: Of 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). CONCLUSION: Systematically including CTP in acute stroke admission imaging protocols may increase the diagnosis of VO and rate of EVT.

Monocyte-to-Lymphocyte Ratio in Clot Analysis as a Marker of Cardioembolic Stroke Etiology.

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.

Predictors of Functional Outcome After Thrombectomy in Patients With Prestroke Disability in Clinical Practice.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) in ischemic stroke patients with poor prestroke conditions remains controversial. We aimed to analyze the frequency of previously disabled patients treated with MT in clinical practice, the safety and clinical response to MT of patients with preexisting disability, and the disabled patient characteristics associated with a better response to MT. METHODS: We studied all consecutive patients with anterior circulation occlusion treated with MT from January 2017 to December 2019 included in the Codi Ictus Catalunya registry-a government-mandated, prospective, hospital-based data set. Prestroke disability was defined as modified Rankin Scale score 2 or 3. Functional outcome at 90 days was centrally assessed by a blinded evaluator of the Catalan Stroke Program. Favorable outcome (to return at least to prestroke modified Rankin Scale at 90 days) and safety and secondary outcomes were compared with patients without previous disability. Logistic regression analysis was used to assess the association between prestroke disability and outcomes and to identify a disabled patient profile with favorable outcome after MT. RESULTS: Of 2487 patients included in the study, 409 (17.1%) had prestroke disability (313 modified Rankin Scale score 2 and 96 modified Rankin Scale score 3). After adjustment for covariates, prestroke disability was not associated with a lower chance of achieving favorable outcome at 90 days (24% versus 30%; odds ratio, 0.79 [0.57-1.08]), whereas it was independently associated with a higher risk of symptomatic intracranial hemorrhage (5% versus 3%; odds ratio, 2.04 [1.11-3.72]) and long-term mortality (31% versus 18%; odds ratio, 1.74 [1.27-2.39]) compared with patients without disability. Prestroke disabled patients without diabetes, Alberta Stroke Program Early CT Score >8 and National Institutes of Health Stroke Scale score <17 showed similar safety and outcome results after MT as patients without prestroke disability. CONCLUSIONS: Despite a higher mortality and risk of symptomatic intracranial hemorrhage, prestroke-disabled patients return as often as independent patients to their prestroke level of function, especially those nondiabetic patients with favorable early ischemic signs profile. These data support a potential benefit of MT in patients with previous mild or moderate disability after large anterior vessel occlusion stroke.

Direct to Angiography Suite Without Stopping for Computed Tomography Imaging for Patients With Acute Stroke: A Randomized Clinical Trial.

Importance: Direct transfer to angiography suite (DTAS) for patients with suspected large vessel occlusion (LVO) stroke has been described as an effective and safe measure to reduce workflow time in endovascular treatment (EVT). However, it is unknown whether DTAS improves long-term functional outcomes. Objective: To explore the effect of DTAS on clinical outcomes among patients with LVO stroke in a randomized clinical trial. Design, Setting, and Participants: The study was an investigator-initiated, single-center, evaluator-blinded randomized clinical trial. Of 466 consecutive patients with acute stroke screened, 174 with suspected LVO acute stroke within 6 hours of symptom onset were included. Enrollment took place from September 2018 to November 2020 and was stopped after a preplanned interim analysis. Final follow-up was in February 2021. Interventions: Patients were randomly assigned (1:1) to follow either DTAS (89 patients) or conventional workflow (85 patients received direct transfer to computed tomographic imaging, with usual imaging performed and EVT indication decided) to assess the indication of EVT. Patients were stratified according to their having been transferred from a primary center vs having a direct admission. Main Outcomes and Measures: The primary outcome was a shift analysis assessing the distribution of the 90-day 7-category (from 0 [no symptoms] to 6 [death]) modified Rankin Scale (mRS) score among patients with LVO whether or not they received EVT (modified intention-to-treat population) assessed by blinded external evaluators. Secondary outcomes included rate of EVT and door-to-arterial puncture time. Safety outcomes included 90-day mortality and rates of symptomatic intracranial hemorrhage. Results: In total, 174 patients were included, with a mean (SD) age of 73.4 (12.6) years (range, 19-95 years), and 78 patients (44.8%) were women. Their mean (SD) onset-to-door time was 228.0 (117.9) minutes, and their median admission National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21). In the modified intention-to-treat population, EVT was performed for all 74 patients in the DTAS group and for 64 patients (87.7%) in the conventional workflow group (P = .002). The DTAS protocol decreased the median door-to-arterial puncture time (18 minutes [IQR, 15-24 minutes] vs 42 minutes [IQR, 35-51 minutes]; P < .001) and door-to-reperfusion time (57 minutes [IQR, 43-77 minutes] vs 84 minutes [IQR, 63-117 minutes]; P < .001). The DTAS protocol decreased the severity of disability across the range of the mRS (adjusted common odds ratio, 2.2; 95% CI, 1.2-4.1; P = .009). Safety variables were comparable between groups. Conclusions and Relevance: For patients with LVO admitted within 6 hours after symptom onset, this randomized clinical trial found that, compared with conventional workflow, the use of DTAS increased the odds of patients undergoing EVT, decreased hospital workflow time, and improved clinical outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT04001738.

Ischemic Core Overestimation on Computed Tomography Perfusion.

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 <30%, as compared with contralateral hemisphere. Collateral status was assessed using the hypoperfusion intensity ratio (defined by the proportion of the time to maximum of tissue residue function >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, 0­27) and 20 mL (interquartile range, 5­55), respectively. Median hypoperfusion intensity ratio was 0.46 (interquartile range, 0.23­0.59). Eighty-three patients (20%) presented ischemic core overestimation (median overestimation, 12 mL [interquartile range, 41­5]). 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, 1.20­1.65]) and earlier onset to imaging time (per 60 minutes earlier; adjusted odds ratio, 1.14 [CI, 1.04­1.25]) 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, 0.96­1.44]). Poor collateral status influence on core overestimation differed according to onset to imaging time, with a stronger size of effect on early imaging patients(Pinteraction <0.01). 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.

Defining a Target Population to Effectively Test a Neuroprotective Drug.

BACKGROUND AND PURPOSE: We aim to identify the subgroup of acute ischemic stroke patients with higher probabilities of benefiting from a potential neuroprotective drug using baseline outcome predictors and test whether different selection criteria strategies can improve detected treatment effect. METHODS: We analyzed the association between final infarct volume (FIV), measured on 24- to 72-hour computed tomography, and National Institutes of Health Stroke Scale at discharge/day 5 of acute stroke patients who underwent endovascular treatment. Models were adjusted for age, sex, and affected hemisphere. We analyzed the impact of absolute (5-15 mL) and relative (33%) FIV reductions in the National Institutes of Health Stroke Scale in the whole population and in different subsets of patients selected according to baseline imaging criteria using computed tomography perfusion. RESULTS: We analyzed 627 patients; association between FIV and 5-day National Institutes of Health Stroke Scale was best described with a quadratic function, with a regression coefficient ß=1.56 ([95% CI, 1.45-1.67] P<0.001) in the adjusted analysis. In the models considering a fixed absolute (5/15 mL) FIV reduction, treatment effect was highest when patients with predicted larger FIV were excluded, whereas in a 33% FIV reduction model, treatment effect increased with the exclusion of patients with expected excellent outcomes. CONCLUSIONS: Patients either with excellent outcomes after endovascular thrombectomy or with large infarcts may dilute the treatment effect in stroke neuroprotective drug trials. Computed tomography perfusion on admission may help selecting adequate patients according to expected drug effect profile.

Leptomeningeal Collateral Flow Modifies Endovascular Treatment Efficacy on Large-Vessel Occlusion Strokes.

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.

SAA (Serum Amyloid A): A Novel Predictor of Stroke-Associated Infections.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate and independently validate SAA (serum amyloid A)-a recently discovered blood biomarker-to predict poststroke infections. METHODS: The derivation cohort (A) was composed of 283 acute ischemic stroke patients and the independent validation cohort (B), of 367 patients. The primary outcome measure was any stroke-associated infection, defined by the criteria of the US Centers for Disease Control and Prevention, occurring during hospitalization. To determine the association of SAA levels on admission with the development of infections, logistic regression models were calculated. The discriminatory ability of SAA was assessed, by calculating the area under the receiver operating characteristic curve. RESULTS: After adjusting for all predictors that were significantly associated with any infection in the univariate analysis, SAA remained an independent predictor in study A (adjusted odds ratio, 1.44 [95% CI, 1.16-1.79]; P=0.001) and in study B (adjusted odds ratio, 1.52 [1.05-2.22]; P=0.028). Adding SAA to the best regression model without the biomarker, the discriminatory accuracy improved from 0.76 (0.69-0.83) to 0.79 (0.72-0.86; P<0.001; likelihood ratio test) in study A. These results were externally validated in study B with an improvement in the area under the receiver operating characteristic curve, from 0.75 (0.70-0.81) to 0.76 (0.71-0.82; P<0.038). CONCLUSIONS: Among patients with ischemic stroke, blood SAA measured on admission is a novel independent predictor of infection after stroke. SAA improved the discrimination between patients who developed an infection compared with those who did not in both derivation and validation cohorts. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00390962.

COVID-19 and Stroke: Incidence and Etiological Description in a High-Volume Center.

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.

Complicación trombótica de neumonía grave por COVID-19: ictus por embolismo paradójico atípico / Thrombotic complication of severe COVID-19 pneumonia: stroke due to atypical paradoxical embolism

INTRODUCCIÓN: La infección grave por el SARS-CoV-2 ha demostrado un incremento del riesgo de fenómenos trombóticos, especialmente venosos. Los catéteres venosos centrales también se han asociado a un mayor riesgo de complicaciones trombóticas. El embolismo paradójico como mecanismo etiológico del ictus isquémico debe tenerse en cuenta en un contexto protrombótico elevado, en el que puede ser más frecuente. CASO CLÍNICO: Mujer de 40 años, portadora de un catéter venoso central, con ictus isquémico de gran vaso, tratada con trombectomía mecánica por embolismo paradójico atípico durante el ingreso en cuidados intensivos por neumonía bilateral por COVID-19. Dentro del estudio etiológico, destacaba analíticamente una elevación del dímero D y shunt derecha-izquierda con paso masivo de contraste directamente desde la vía central de acceso periférico en la extremidad superior izquierda a la aurícula izquierda en el ecocardiograma transesofágico. Una angiotomografía torácica mostró una estructura venosa anómala con origen en la vena subclavia y drenaje a la vena segmentaria del lóbulo superior izquierdo con vaciado directo a la aurícula izquierda. Se decidió anticoagulación hasta la retirada del catéter venoso central y antiagregación simple al alta. CONCLUSIONES: El embolismo paradójico por shunt intra o extracardíaco debe considerarse en pacientes con COVID-19, dado el elevado riesgo tromboembólico venoso asociado. Para definir el manejo profiláctico y terapéutico óptimo son necesarios más estudios

INTRODUCTION: Severe infection by SARS-CoV-2 has shown to entail an increased risk of thrombotic, especially venous, events. Central venous catheters have also been associated with an increased risk of thrombotic complications. Paradoxical embolism as an aetiological mechanism of ischaemic stroke should be considered in a highly prothrombotic context, where it may be more frequent. CASE REPORT: A 40-year-old woman with a central venous catheter, with a large vessel ischaemic stroke, treated with mechanical thrombectomy for an atypical paradoxical embolism while in intensive care for bilateral COVID-19 pneumonia. In the aetiological study, analysis highlighted an elevation of the D-dimer and right-left shunt with massive passage of contrast directly from the central peripheral access pathway in the left upper extremity to the left atrium in the transoesophageal echocardiogram. Thoracic tomographic angiography showed an anomalous venous structure with its origin in the subclavian vein and drainage to the segmental vein of the left upper lobe with direct emptying into the left atrium. Treatment consisted in anticoagulation until removal of the central venous catheter and simple anti-aggregating medication on discharge. CONCLUSIONS: Paradoxical embolism due to intra- or extra-cardiac shunt should be considered in patients with COVID-19, given the high associated risk of venous thromboembolism. Further studies are needed to be able to define optimal prophylactic and therapeutic management

Screening of Embolic Sources by Point-of-Care Ultrasound in the Acute Phase of Ischemic Stroke.

Our objective was to evaluate hand-held echocardiography as point of care ultrasound scanning (POCUS) to detect sources of embolism in the acute phase of stroke. Prospective, unicentric observational cohort study of non-lacunar ischemic stroke patients evaluated by V Scan device. The main sources of embolism (MSEs) were classified into embolic valvulopathies and severe ventricular dysfunction. We looked for atrial fibrillation (AF) predictors in strokes of undetermined etiology. MSEs were detected in 19.23% (25/130). Large vessel occlusion (LVO) (odds ratio [OR]: 4.24, 95% confidence interval [CI]: 1.01-17.85) and chronic heart failure (OR: 13.25, 95% CI: 3.54-49.50) were independent predictors of MSEs. LVO (OR: 6.54, 95% CI: 1.62-26.27) and left atrial area >20 cm2 (OR: 7.01, 95% CI: 1.75-28.09) independently predicted AF. Patients with LVO and chronic heart disease may benefit from hand-held echocardiography as part of POCUS in the acute phase of ischemic stroke. Left atrial area measured was an independent predictor of AF in strokes of undetermined etiology.

Computed Tomography Perfusion After Thrombectomy: An Immediate Surrogate Marker of Outcome After Recanalization in Acute Stroke.

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<0.01). Smaller hypoperfusion volumes on CTPpost were observed in patients with DCR (0 cc [0-13] versus non-DCR 8 cc [0-56]; P<0.01) or favorable outcome (modified Rankin Scale score 0-2: 0 cc [0-13] versus 7 [0-56] cc; P<0.01). No associations were detected with hyperperfusion pattern. An hypoperfusion volume <3.5 cc emerged as independent predictor of DCR (OR, 4.1 [95% CI, 2.0-8.3]; P<0.01) and 3 months favorable outcome (OR, 3.5 [95% CI, 1.6-7.8]; P<0.01). 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.

Time Matters: Adjusted Analysis of the Influence of Direct Transfer to Angiography-Suite Protocol in Functional Outcome.

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<0.01). DTAS patients presented lower National Institutes of Health Stroke Scale score at 24 hours (9 [3.5-17] versus 14 [5-19]; P=0.01) and a lower rate of symptomatic hemorrhagic transformation (4.6% versus 10.9%, P<0.03). At 90 days, DTAS patients had a higher rate of good functional outcome (43% versus 29%; odds ratio, 1.81 [95% CI, 1.14-2.87]; 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<0.01), but not in patients admitted in the 3 to 6 hours window (n=193, odds ratio, 1.37 [95% CI, 0.72-2.60]; 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.