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Background: The impact of thrombolytics directed towards different thrombus components regarding site of occlusion in combination with mechanical thrombectomy (MT) to achieve endovascular complete recanalization is unclear., Methods: Retrospective analysis of a prospective database in two stroke centers. Intracranial thrombi retrieved by MT were analyzed using hematoxylin-eosin staining for fibrin and red blood cell proportions, and CD61 immunostaining for platelets proportion in thrombus (PLTPT) assessment. Thrombi composition, baseline variables, etiology, treatment features and occlusion location were analyzed., Results: Overall, 221 patients completed the per protocol analysis and 110 cases achieved a final expanded Thrombolysis in Cerebral Infarction (eTICI) 3 (49%) of which 70 were MT (32%) by first pass effect (FPE). Thrombi from medium distal vessel occlusions had higher PLTPT compared with thrombi from proximal large vessel occlusions (68% vs 61%, P=0.026). In particular, middle cerebral artery M2-M3 segment thrombi had the highest PLTPT (70%), and basilar artery thrombi the lowest PLTPT (41%). After logistic regression analysis adjusted for occlusion location and intravenous fibrinolysis, lower baseline National Institutes of Health Stroke Scale score (adjusted OR (aOR) 0.95, 95% CI 0.913 to 0.998) and PLTPT (aOR 0.97, 95% CI 0.963 to 0.993) were independently associated with FPE. Fewer MT passes (aOR 0.67, 95% CI 0.538 to 0.842) and platelet poor thrombus (<62% PLTPT; aOR 2.39, 95% CI 1.288 to 4.440) were independently associated with final eTICI 3., Conclusions: Occlusion location might be a surrogate parameter for thrombus composition. Platelet poor clots and fewer MT passes were independently associated with complete endovascular recanalization. Clinical trials testing the benefits of combining selective intra-arterial platelet antagonists with MT to improve endovascular outcomes are warranted., Competing Interests: Competing interests: MR reported receiving personal fees from Anaconda Biomed, AptaTargets, Cerenovus, Johnson & Johnson, Medtronic, Methinks, Philips, Sanofi, Stryker, and Rapid AI outside the submitted work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

We present the case of a 64-year-old female with personal history of breast carcinoma diagnosed in 2011, treated and discharged from the Oncology service after 10 years disease-free who, 21 years after the diagnosis, undergoes a colonoscopy with biopsy sampling due to a 2-year period of diarrhea and weight loss, which histological study show infiltration of the large intestine's by breast carcinoma. Due to the usual lymphatic widespread, metastases of breast cancer in the gastrointestinal tract are extremely rare with nonspecific symptoms, long latency periods and poor prognosis.

In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect in preclinical models of stroke and a very good pharmacokinetic and safety profile in healthy volunteers, is a promising first-in-class aptamer with the potential to address this huge unmet need. This protocol establishes the clinical trial procedures to conduct a Phase Ib/IIa clinical study (APRIL) to assess ApTOLL tolerability, safety, pharmacokinetics, and biological effect in patients with AIS who are eligible for EVT. This will be a multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to evaluate the administration of ApTOLL together with EVT in patients with AIS. The study population will be composed of men and non-pregnant women with confirmed AIS with a <6h window from symptoms onset to ApTOLL/placebo administration. The trial is currently being conducted and is divided into two parts: Phase Ib and Phase IIa. In Phase Ib, 32 patients will be allocated to four dose ascending levels to select, based on safety criteria, the best two doses to be administered in the following Phase IIa in which 119 patients will be randomized to three arms of treatment (dose A, dose B, and placebo)., Identification of the Trial: EudraCT: 2020-002059-38 and ClinicalTrials.gov Identifier: NCT04734548 https://clinicaltrials.gov/ct2/show/NCT04734548?term=ApTOLL&cond=Stroke&draw=2&rank=1., Competing Interests: MH-J is an employee of AptaTargets S.L. MR receives payment from Philips as co-principal investigator of the WE TRUST study and he has a consulting agreement with Medtronic, Stryker, Cerenovus, CVAid, Methinks, Anaconda Biomed, and AptaTargets S.L. JC is founder and CEO of Aldebaran Health Intelligence, S.L. MD is employed by Cureteq AG and has provided consultancy services for AptaTargets S.L. BJ is a consultant to AptaTargets S.L. and Guardian Therapeutics, Inc. FA-S has been consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, AptaTargets, Chemo, Cinfa, FAES Farma, Farmalíder, Ferrer, GlaxoSmithKline, Galenicum, Gilead, Italfarmaco, Janssen-Cilag, Kern Pharma, Normon, Novartis, Servier, Silverpharma, Teva, and Zambon. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hernández-Jiménez, Abad-Santos, Cotgreave, Gallego, Jilma, Flores, Jovin, Vivancos, Molina, Montaner, Casariego, Dalsgaard, Hernández-Pérez, Liebeskind, Cobo and Ribo.)

Background: We studied the evolution over time of diffusion weighted imaging (DWI) lesion volume and the factors involved on early and late infarct growth (EIG and LIG) in stroke patients undergoing endovascular treatment (EVT) according to the final revascularization grade., Methods: This is a prospective cohort of patients with anterior large artery occlusion undergoing EVT arriving at 1 comprehensive stroke center. Magnetic resonance imaging was performed on arrival (pre-EVT), <2 hours after EVT (post-EVT), and on day 5. DWI lesions and perfusion maps were evaluated. Arterial revascularization was assessed according to the modified Thrombolysis in Cerebral Infarction (mTICI) grades. We recorded National Institutes of Health Stroke Scale at arrival and at day 7. EIG was defined as (DWI volume post-EVT-DWI volume pre-EVT), and LIG was defined as (DWI volume at 5d-DWI volume post-EVT). Factors involved in EIG and LIG were tested via multivariable lineal models., Results: We included 98 patients (mean age 70, median National Institutes of Health Stroke Scale score 17, final mTICI≥2b 86%). Median EIG and LIG were 48 and 63.3 mL in patients with final mTICI<2b, and 3.6 and 3.9 cc in patients with final mTICI≥2b. Both EIG and LIG were associated with higher National Institutes of Health Stroke Scale at day 7 ( ρ =0.667; P <0.01 and ρ =0.614; P <0.01, respectively). In patients with final mTICI≥2b, each 10% increase in the volume of DWI pre-EVT and each extra pass leaded to growths of 9% (95% CI, 7%-10%) and 14% (95% CI, 2%-28%) in the DWI volume post-EVT, respectively. Furthermore, each 10% increase in the volume of DWI post-EVT, each extra pass, and each 10 mL increase in TMax6s post-EVT were associated with growths of 8% (95% CI, 6%-9%), 9% (95% CI, 0%-19%), and 12% (95% CI, 5%-20%) in the volume of DWI post-EVT, respectively., Conclusions: Infarct grows during and after EVT, especially in nonrecanalizers but also to a lesser extent in recanalizers. In recanalizers, number of passes and DWI volume influence EIG, while number of passes, DWI, and hypoperfused volume after the procedure determine LIG.

Objective: This study was undertaken to investigate whether adjunct alteplase improves brain reperfusion following successful thrombectomy., Methods: This single-center, randomized, double-blind, placebo-controlled study included 36 patients (mean [standard deviation] = 70.8 [13.5] years old, 18 [50%] women) with large vessel occlusion undergoing thrombectomy resulting in near-normal (expanded Thrombolysis in Cerebral Infarction [eTICI] b50/67/2c, n = 23, 64%) or normal angiographic reperfusion (eTICI 3, n = 13, 36%). Seventeen patients were randomized to intra-arterial alteplase (0.225mg/kg), and 19 received placebo. At 48 hours, patients had brain perfusion/diffusion-weighted magnetic resonance imaging (MRI) and MRI-spectroscopy. The primary outcome was the difference in the proportion of patients with areas of hypoperfusion on MRI. Secondary outcomes were the infarct expansion ratio (final to initial infarction volume), and the N-acetylaspartate (NAA) peak relative to total creatine as a marker of neuronal integrity., Results: The prevalence of hypoperfusion was 24% with intra-arterial alteplase, and 58% with placebo (adjusted odds ratio = 0.20, 95% confidence interval [CI] = 0.04-0.91, p = 0.03). Among 14 patients with final eTICI 3 scores, hypoperfusion was found in 1 of 7 (14%) in the alteplase group and 3 of 7 (43%) in the placebo group. Abnormal brain perfusion was associated with worse functional outcome at day 90. Alteplase significantly reduced the infarct expansion ratio compared with placebo (median [interquartile range (IQR)] = 0.7 [0.5-1.2] vs 3.2 [1.8-5.7], p = 0.01) and resulted in higher NAA peaks (median [IQR] = 1.13 [0.91-1.36] vs 1.00 [0.74-1.22], p < 0.0001)., Interpretation: There is a high prevalence of areas of hypoperfusion following thrombectomy despite successful reperfusion on angiography. Adjunct alteplase enhances brain reperfusion, which results in reduced expansion of the infarction and improved neuronal integrity. ANN NEUROL 2022;92:860-870., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke., Methods: In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants., Findings: Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047)., Interpretation: Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients., Funding: Medtronic and University Hospital Bern., Competing Interests: Declaration of interests UF reports financial support for the present study from Medtronic; research grants from Medtronic BEYOND SWIFT registry, the Swiss National Science Foundation, and the Swiss Heart Foundation; consulting fees from Medtronic, Stryker, and CSL Behring (fees paid to institution); has membership of a data safety monitoring board for the IN EXTREMIS trial and the TITAN trial; was on the advisory board for Portola (Alexion; fees paid to institution); and is Vice President of the Swiss Neurological Society. JK reports financial support from Medtronic for the BEYOND SWIFT registry (fees paid to institution); and research grants from the Swiss National Science Foundation supporting the TECNO trial (fees paid to institution), Swiss Academy of Medical Sciences supporting MRI research (fees paid to institution), and Swiss Heart Foundation supporting cardiac MRI in the aetiological work-up of stroke patients (fees paid to institution). CC reports consulting fees from Medtronic. PMo reports research funding (fees paid to institution) from the Swiss National Science Foundation, the Swiss Heart Foundation, and Medtronic. GM reports consulting fees from Stryker Neurovascular; and was paid for lectures for Medtronic and Microvention Europe. IS reports consulting fees from Sanofi Synthé-Labo, Servier, Boheringer Ingelheim, AstraZeneca, Novonordisk, and Medtronic; and payment or honoraria from Sanofi Synthé-Labo, Medtronic, Boheringer Ingelheim, AstraZeneca, and BMS—Pfizer. ON reports funding from a Stryker Research grant; and payment or honoraria for lectures for Phenox and Stryker. MR reports consulting fees from Medtronic, Stryker, Cerenovus, Philips, and Apta Targets; payment or honoraria from Ischemia View; participates on a data safety monitoring board or advisory board of Sensome; and has stock or stock options in Anaconda Biomed, CVAid, and Methinks. EC reports grants from the Swiss Heart Foundation and Swiss National Science Foundation, not related to the present study. ARL reports grants from the University of Zurich, the LOOP Zurich, and P&K Pühringer Foundation; consulting fees from Bayer; and a lecture honorarium from Moleac Pte, Singapore. WP reports grants from the German Research Foundation, LOEWE (research funding of the federal state of Hesse); royalties or licenses from the Stroke Team Training (Laerdal Medical); payment or honoraria from Laerdal Medical, Alexion, Pfizer—BMS, and Stryker Neurovascular; and support for attending meetings or travel from Laerdal Medical, Alexion, Pfizer—BMS, and Stryker Neurovascular. MA reports honoraria for lectures from AstraZeneca, Bayer, Covidien, Medtronic, and Sanofi; and participates on scientific advisory boards of Amgen, Bayer, BMS, Daiichi Sankyo, Medtronic, and Pfizer. AHS reports being a coinvestigator for the US National Institutes of Health (1R01EB030092-01); is mentor for the Carol W Harvey Chair of Research and Sharon Epperson Chair of Research at the Brain Aneurysm Foundation; receipt of consulting fees from Amnis Therapeutics, Apellis Pharmaceuticals, Boston Scientific, Canon Medical Systems USA, Cardinal Health 200, Cerebrotech Medical Systems, Cerenovus, Cerevatech Medical, Cordis, Corindus, Endostream Medical, Imperative Care, InspireMD, Integra, IRRAS AB, Medtronic, MicroVention, Minnetronix Neuro, Peijia Medical, Penumbra, Q’Apel Medical, Rapid Medical, Serenity Medical, Silk Road Medical, StimMed, Stryker Neurovascular, Three Rivers Medical, VasSol, and Viz.ai; is Secretary of the Board of the Society of NeuroInterventional Surgery 2020–2021 (unpaid); is Chair of the Cerebrovascular Section of the AANS/CNS 2020–2021 (unpaid); has stock or stock options in Adona Medical, Amnis Therapeutics, Bend IT Technologies, BlinkTBI, Cerebrotech Medical Systems, Cerevatech Medical, Cognition Medical, CVAID, E8, Endostream Medical, Galaxy Therapeutics, Imperative Care, InspireMD, Instylla, International Medical Distribution Partners, Launch NY, NeuroRadial Technologies, NeuroTechnology Investors, Neurovascular Diagnostics, Peijia Medical, PerFlow Medical, Q’Apel Medical, QAS.ai, Radical Catheter Technologies, Rebound Therapeutics (purchased 2019 by Integra Lifesciences), Rist Neurovascular, (purchased 2020 by Medtronic), Sense Diagnostics, Serenity Medical, Silk Road Medical, Sim & Cure, SongBird Therapy, Spinnaker Medical, StimMed, Synchron, Three Rivers Medical, Truvic Medical, Tulavi Therapeutics, Vastrax, VICIS, and Viseon; and other financial or non-financial interests: national principal investigator or steering committees for Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE and SWIFT DIRECT Trials; MicroVention FRED Trial and CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial, MIVI neuroscience EVAQ Trial; Rapid Medical SUCCESS Trial; and InspireMD C-GUARDIANS IDE Pivotal Trial. MTF reports research grants from Medtronic, Siemens, Genentech, Idorsia, and Vesalio; consulting fees from Genentech, Balt USA, CereNovus, and Oculus Imaging; and participates on a data safety monitoring board or advisory board for Balt USA, Jacobs Institute, and Imperative Care. MW reports a grant from Stryker Neurovascular; consulting fees from Stryker Neurovascular; payment or honoraria from Stryker Neurovascular and Bracco Imaging; is board member for the German Society of Neuroradiology (no payments); and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Ab medica, Acandis, Bracco Imaging, Cerenovus, Kaneka Pharmaceuticals, Medtronic, Mentice, Phenox, and Stryker Neurovascular (support to institution). PMa reports grants from the Swiss National Science Foundation; consulting fees from Medtronic and Stryker; payment or honoraria from Medtronic and Stryker; and participated on a data safety monitoring board or advisory board of MicroVention. H-CD reports honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from Abbott, BMS, Boehringer Ingelheim, Daiichi-Sankyo, Novo-Nordisk, Pfizer, Portola, and WebMD Global; financial support for research projects from Boehringer Ingelheim; received research grants from the German Research Council and German Ministry of Education and Research; serves as Editor of Neurologie up2date, InFo Neurologie & Psychiatrie, Arzneimitteltherapie, and coeditor of Cephalalgia; and is on the editorial board of The Lancet Neurology and Drugs. MM reports payment or honoraria from Boehringer Ingelheim. DSL reports consulting fees from Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical as imaging core laboratory. JLS reports funding for the present study from Medtronic; consulting fees from Cerenovus; participates on a data safety monitoring board or advisory board for MIVI and Phillips; and has stock or stock options in Rapid Medical. JG reports a Swiss National Funds grant for MRI in stroke. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Large-bore aspiration catheters enabling greater flow rates and suction force for mechanical thrombectomy might improve outcomes in patients with stroke secondary to large-vessel occlusion. Complete or near-complete reperfusion after a single thrombectomy pass (first-pass effect) is associated with improved clinical outcomes. We assessed the efficacy and safety of novel MIVI Q™ aspiration catheters in combination with stent-retriever devices., Methods: We retrospectively analyzed demographics, procedure characteristics, and clinical data from consecutive patients with acute anterior large-vessel occlusion treated with a combined approach using MIVI Q™ aspiration catheters and stent retrievers. Reperfusion was defined according to the modified thrombolysis in cerebral infarction (mTICI) score. Clinical outcomes were measured by the National Institute of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores., Results: We included 52 patients (median age, 75 y IQR: 64-83); 31 (59.6%) women; 14 (26.9%) with terminal internal carotid artery occlusions, 26 (50%) middle cerebral artery (MCA) segment M1 occlusions, and 12 (23.1%) MCA segment M2 occlusions; median NIHSS score at admission was 19 (IQR: 13-22). After the first pass, 25 (48%) patients had mTICI ≥ 2c. At the end of the procedure, 47 (90.4%) had mTICI ≥ 2b and 35 (67.3%) had mTICI ≥ 2c. No serious device-related adverse events were observed. Symptomatic intracranial hemorrhage developed in 1 patient. Mean NIHSS score was 13 at 24 h and 5 at discharge. At 90 days, 24 (46.2%) patients were functionally independent (mRS 0-2)., Conclusion: This preliminary study found good efficacy and safety for MIVI Q™ aspiration catheters used in combination with stent-retriever devices., (© 2021. The Author(s).)

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.

Introduction: hepatitis C patients loss to follow-up in the health care system has been shown to have negative consequences. This study aimed to investigate this issue as regards primary biliary cholangitis., Methods: the databases (immunology, biochemistry, clinical reports, drug dispensation, appointments) of 4 reference hospitals in Spain (serving a population of 1,450,000 inhabitants) were analyzed. The diagnosis of primary biliary cholangitis was based on an antimitochondrial antibody titer ≥ 1:80, chronically elevated alkaline phosphatase, and the absence of other liver disease. Patients were classified as lost in the absence of reports indicating a diagnosis, specific medical follow-up, and/or treatment with bile salts., Results: a total of 1372 patients with antimitochondrial antibody titers ≥ 1:80 were included between January 2010 and June 2019. A total of 697 (50.8 %) were classified as having primary biliary cholangitis, and 100 patients (14.3 %; 95 % CI: 11.8-17.2) were identified as lost. Of these, 30 were contacted and retrieved. The median age was 70 years, 93 % were female, median alkaline phosphatase was 185 IU/L, 10 % had pruritus, and 27 % had a transient elastography value > 9.5 kPa. The disease was confirmed and ursodeoxycholic acid was started in all 30 patients. Death was liver-related in 6 of the 100 patients classified as lost., Conclusion: up to 14.3 % of patients (1 out of 7) with a definitive diagnosis of primary biliary cholangitis remain undiagnosed, thus preventing monitoring and treatment. More than a quarter are at risk of advanced liver disease and its complications. Patients lost in the system must be identified and retrieved, and searching hospital databases is a suitable approach to meet this goal.

Background: Previously published retrospective series show a high prevalence of fecal incontinence (FI) in stroke patients. We aimed to analyze in a prospective series the current incidence of FI in acute stroke in functionally independent patients and its evolution over time and the patient characteristics associated with the appearance of FI in acute stroke. Methods: We included consecutive patients with acute stroke admitted in our stroke unit who fulfilled the following inclusion criteria: a first episode of stroke, aged >18 years, with no previous functional dependency [modified Rankin Scale (mRS) ≤ 2] and without previous known FI. FI was assessed by a multidisciplinary trained team using dedicated questionnaires at 72 ± 24 h (acute phase) and at 90 ± 15 days (chronic phase). Demographic, medical history, clinical and stroke features, mortality, and mRS at 7 days were collected. Results: Three hundred fifty-nine (48.3%) of 749 patients (mean age 65.9 ± 10, 64% male, 84.1% ischemic) fulfilled the inclusion criteria and were prospectively included during a 20-month period. FI was identified in 23 patients (6.4%) at 72 ± 24 h and in 7 (1.9%) at 90 days ± 15 days after stroke onset. FI was more frequent in hemorrhagic strokes (18 vs. 5%, p 0.007) and in more severe strokes [median National Institute of Health Stroke Scale (NIHSS) 18 (14-22) vs. 5 (3-13), p < 0.0001]. No differences were found regarding age, sex, vascular risk factors, or other comorbidities, or affected hemisphere. Patients with NIHSS ≥12 (AUC 0.81, 95% CI 0.71 to 0.89) had a 17-fold increase for the risk of FI (OR 16.9, IC 95% 4.7-60.1) adjusted for covariates. Conclusions: At present, the incidence of FI in acute stroke patients without previous functional dependency is lower than expected, with an association of a more severe and hemorrhagic stroke. Due to its impact on the quality of life, it is necessary to deepen the knowledge of the underlying mechanisms to address therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lucente, Corral, Rodríguez-Esparragoza, Castañer, Ortiz, Piqueras, Broto, Hernández-Pérez, Domenech, Martinez-Piñeiro, Serra, Almendrote, Parés and Millán.)

Background: The impact of general anesthesia on functional outcome in patients with large vessel occlusion remains unclear. Most studies have focused on anterior circulation large vessel occlusion; however, little is known about the effect of general anesthesia in patients with posterior circulation-large vessel occlusion., Methods: We performed a retrospective analysis from the prospective CICAT registry. All patients with posterior circulation-large vessel occlusion-and undergoing endovascular therapy between January 2016 and January 2020 were included. Demographics, baseline characteristics, procedural data, and anesthesia modality (general anesthesia or conscious sedation) were evaluated. The primary outcome was the proportion of patients with good clinical outcome (modified Rankin Scale score of 0-2) at three months., Results: 298 patients underwent endovascular treatment with posterior circulation-large vessel occlusion-were included. Age, diabetes mellitus, renal insufficiency, baseline National Institutes of Health Stroke Scale score, puncture to recanalization length, ≥3 device passes, absent of successful recanalization (defined as treatment in cerebral ischemia of 3), and general anesthesia were statistically associated with poor outcome (mRS: 3-6). In the multivariable regression, general anesthesia and ≥3 device passes were independently associated with poor outcome (aOR: 3.11, (95% CI: 1.34-7.2); P  = 0.01 and 3.77, (95% CI: 1.29-11.01); P  = 0.02, respectively). Patients treated with general anesthesia were less likely to have a good outcome at three months compared to conscious sedation (19.7% vs. 45.1%, P  < 0.001)., Conclusions: In our study population, general anesthesia use is associated with poor clinical outcome in patients with posterior circulation-large vessel occlusion-treated endovascularly.

Stroke is a major cause of disability and death globally, and prediction of mortality represents a crucial challenge. We aimed to identify blood biomarkers measured during acute ischemic stroke that could predict long-term mortality. Nine hundred and forty-one ischemic stroke patients were prospectively recruited in the Stroke-Chip study. Post-stroke mortality was evaluated during a median 4.8-year follow-up. A 14-biomarker panel was analyzed by immunoassays in blood samples obtained at hospital admission. Biomarkers were normalized and standardized using Z -scores. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with long-term mortality and mortality due to stroke. In the multivariate analysis, the independent predictors of long-term mortality were age, female sex, hypertension, glycemia, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Independent blood biomarkers predictive of long-term mortality were endostatin > quartile 2, tumor necrosis factor receptor-1 (TNF-R1) > quartile 2, and interleukin (IL)-6 > quartile 2. The risk of mortality when these three biomarkers were combined increased up to 69%. The addition of the biomarkers to clinical predictors improved the discrimination (integrative discriminative improvement (IDI) 0.022 (0.007-0.048), p < 0.001). Moreover, endostatin > quartile 3 was an independent predictor of mortality due to stroke. Altogether, endostatin, TNF-R1, and IL-6 circulating levels may aid in long-term mortality prediction after stroke.

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

Objective: Blood biomarkers have not been widely investigated in poststroke epilepsy. In this study, we aimed to describe clinical factors and biomarkers present during acute stroke and analyze their association with the development of epilepsy at long term., Methods: A panel of 14 blood biomarkers was evaluated in patients with ischemic and hemorrhagic stroke. Biomarkers were normalized and standardized using Z-scores. Stroke and epilepsy-related variables were also assessed: stroke severity, determined by National Institutes of Health Stroke Scale (NIHSS) score, stroke type and cause, time from stroke to onset of late seizures, and type of seizure. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with epilepsy., Results: From a cohort of 1115 patients, 895 patients were included. Mean ± standard deviation (SD) age was 72.0 ± 13.1 years, and 57.8% of patients were men. Fifty-one patients (5.7%) developed late seizures, with a median time to onset of 232 days (interquartile range [IQR] 86-491). NIHSS score ≥8 (P < .001, hazard ratio [HR] 4.013, 95% confidence interval [CI] 2.123-7.586) and a history of early onset seizures (P < .001, HR 4.038, 95% CI 1.802-9.045) were factors independently associated with a risk of developing epilepsy. Independent blood biomarkers predictive of epilepsy were high endostatin levels >1.203 (P = .046, HR 4.300, 95% CI 1.028-17.996) and low levels of heat shock 70 kDa protein-8 (Hsc70) <2.496 (P = .006, HR 3.795, 95% CI 1.476-9.760) and S100B <1.364 (P = .001, HR 2.955, 95% CI 1.534-5.491). The risk of epilepsy when these biomarkers were combined increased to 17%. The area under the receiver-operating characteristic (ROC) curve of the predictive model was stronger when clinical variables were combined with blood biomarkers (74.3%, 95% CI 65.2%-83.3%) than when they were used alone (68.9%, 95% CI 60.3%-77.6%)., Significance: Downregulated S100B and Hsc70 and upregulated endostatin may assist in prediction of poststroke epilepsy and may provide additional information to clinical risk factors. In addition, these data are hypothesis-generating for the epileptogenic process., (© 2020 International League Against Epilepsy.)

Background: Non-invasive biomarkers of cognitive impairment are needed. We aim to evaluate transcranial sonographic markers as predictors of cognitive impairment in a prospective cohort., Objective: To study the changes in the third ventricle diameter and the SN echogenicity between the baseline and the control visit, as well as its association with cognitive performance and the diagnosis of cognitive impairment in a prospective cohort., Methods: From the longitudinal population-based Asymptomatic Intracranial Atherosclerosis Study, we selected those subjects that received a complete transcranial sonography (TCS) and extensive cognitive testing, both at baseline and follow-up. We evaluated third ventricle (IIIv) width, echogenicity of substantia nigra (SN), and temporal changes of these parameters., Results: We included 289 participants with a median follow-up time of 7.16 years. Those subjects who developed cognitive decline (n = 23, 7.96%) had a larger IIIv at baseline than those who did not (0.54±0.14 cm versus 0.41±0.15 cm; p = 0.001). A cut-off point of 0.465 cm for the IIIv width was identified as an independent predictor of long-term cognitive impairment after adjustment for age, gender, educational level, and vascular risk score. Change in IIIv diameter after follow-up was not associated with diagnosis of cognitive impairment. The area of SN and the presence of hyperechogenicity of the SN remained stable over time and was not associated with the diagnosis of cognitive impairment., Conclusion: IIIv width assessed by TCS emerged as an independent predictor of long-term cognitive impairment.

Objective: We tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI., Methods: Patients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses., Results: We recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1-7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6-20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66-0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62-7.4)., Conclusion: Patients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke., Clinicaltrialsgov Identifier: NCT02238470., (© 2019 American Academy of Neurology.)

Background and Aims: Symptomatic intracranial atherosclerosis (ICAS) is associated with a high risk of stroke recurrence and occurrence of other vascular events. However, ICAS has been poorly studied from its asymptomatic stage. The objective of our study was to determine if subclinical intracranial atherosclerosis is associated with long-term incident vascular events in Caucasians., Methods: The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) Study is a population-based study that enrolled 933 subjects with a moderate-high vascular risk and without history of stroke or coronary disease, and determined the prevalence of asymptomatic ICAS and associated risk factors. At baseline visit, carotid atherosclerosis and ICAS were screened by color-coded duplex ultrasound, and moderate-severe stenosis was confirmed by magnetic resonance angiography. At baseline, 8.9% of subjects had asymptomatic ICAS, of whom 3.3% were moderate-severe. In the longitudinal phase, subjects were prospectively followed-up to assess the incidence of a combined primary endpoint of vascular events (stroke, acute coronary syndrome and/or vascular death)., Results: After 7.17 years of follow-up, there were 51 incident cerebrovascular events (16 transient ischemic attacks, 27 ischemic, 8 hemorrhagic strokes), 63 incident coronary events and 23 vascular deaths. After multivariate Cox regression analyses adjusted by age, sex, vascular risk and presence of carotid plaques, ICAS was an independent predictor for overall vascular events (HR 1.83 [1.10-3.03], p = 0.020), and moderate-severe intracranial stenosis was also an independent predictor for cerebrovascular events (HR 2.66 [1.02-6.94], p = 0.046)., Conclusions: Asymptomatic ICAS is independently associated with the incidence of future vascular events in our population. These findings might have implications for the development of primary prevention strategies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome., Methods: In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1, 2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 μm 2 /s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered., Findings: We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0·47 [95% CI 0·30-0·72], p=0·0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0·77 [0·69-0·86] per 10 mL, p interaction =0·29; diffusion MRI OR 0·87 [0·81-0·94] per 10 mL, p interaction =0·94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low., Interpretation: Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imaging-to-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions., Funding: Medtronic., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Blood-brain barrier (BBB) permeability has been proposed as a predictor of hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) administration; however, the reliability of perfusion computed tomography (PCT) permeability imaging for predicting HT is uncertain. We aimed to determine the performance of high-permeability region size on PCT (HPrs-PCT) in predicting HT after intravenous tPA administration in patients with acute stroke., Methods: We performed a multimodal CT protocol (non-contrast CT, PCT, CT angiography) to prospectively study patients with middle cerebral artery occlusion treated with tPA within 4.5 hours of symptom onset. HT was graded at 24 hours using the European-Australasian Acute Stroke Study II criteria. ROC curves selected optimal volume threshold, and multivariate logistic regression analysis identified predictors of HT., Results: The study included 156 patients (50% male, median age 75.5 years). Thirty-seven (23,7%) developed HT [12 (7,7%), parenchymal hematoma type 2 (PH-2)]. At admission, patients with HT had lower platelet values, higher NIHSS scores, increased ischemic lesion volumes, larger HPrs-PCT, and poorer collateral status. The negative predictive value of HPrs-PCT at a threshold of 7mL/100g/min was 0.84 for HT and 0.93 for PH-2. The multiple regression analysis selected HPrs-PCT at 7mL/100g/min combined with platelets and baseline NIHSS score as the best model for predicting HT (AUC 0.77). HPrs-PCT at 7mL/100g/min was the only independent predictor of PH-2 (OR 1, AUC 0.68, p = 0.045)., Conclusions: HPrs-PCT can help predict HT after tPA, and is particularly useful in identifying patients at low risk of developing HT.

Purpose: To assess the reliability of the Fazekas score on brain CT in acute stroke patients., Methods: Two raters evaluated the Fazekas score in 157 CT scans from consecutive patients with acute stroke., Results: The Fazekas scores on brain CT scans showed consistent (weighted κ, 0.73) and moderate (weighted κ, 0.56) interobserver agreement for periventricular and deep white matter areas, respectively. Intraobserver reliability was substantial for both areas (weighted κ, 0.85 and 0.8)., Conclusion: The Fazekas score on CT can be used to reliably grade white matter changes, and can be a useful tool when MRI is not available., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Purpose: Stroke diagnosis could be challenging in the acute phase. We aimed to develop a blood-based diagnostic tool to differentiate between real strokes and stroke mimics and between ischemic and hemorrhagic strokes in the hyperacute phase., Methods: The Stroke-Chip was a prospective, observational, multicenter study, conducted at 6 Stroke Centers in Catalonia. Consecutive patients with suspected stroke were enrolled within the first 6 hours after symptom onset, and blood samples were drawn immediately after admission. A 21-biomarker panel selected among previous results and from the literature was measured by immunoassays. Outcomes were differentiation between real strokes and stroke mimics and between ischemic and hemorrhagic strokes. Predictive models were developed by combining biomarkers and clinical variables in logistic regression models. Accuracy was evaluated with receiver operating characteristic curves., Results: From August 2012 to December 2013, 1308 patients were included (71.9% ischemic, 14.8% stroke mimics, and 13.3% hemorrhagic). For stroke versus stroke mimics comparison, no biomarker resulted included in the logistic regression model, but it was only integrated by clinical variables, with a predictive accuracy of 80.8%. For ischemic versus hemorrhagic strokes comparison, NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) >4.9 (odds ratio, 2.40; 95% confidence interval, 1.55-3.71; P <0.0001) and endostatin >4.7 (odds ratio, 2.02; 95% confidence interval, 1.19-3.45; P =0.010), together with age, sex, blood pressure, stroke severity, atrial fibrillation, and hypertension, were included in the model. Predictive accuracy was 80.6%., Conclusions: The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke., (© 2017 American Heart Association, Inc.)

Background and Purpose: Intracranial carotid artery calcification (ICAC) is a surrogate marker of intracranial arteriosclerosis, which may impact the revascularization and clinical outcome of acute stroke patients who undergo mechanical thrombectomy., Methods: We included 194 patients admitted to our Stroke Unit between January 2009 and September 2015 who underwent mechanical thrombectomy for an anterior circulation occlusion. ICAC was quantified in both intracranial carotid arteries on the nonenhanced computed tomographic scan that was acquired before thrombectomy. Complete arterial revascularization was defined as a Thrombolysis in Cerebral Infarction ≥2b on the final angiographic examination. Poor functional outcome was defined as a modified Rankin Scale score of >2 at 90 days. We assessed the independent effect of ICAC volume on complete arterial revascularization, functional outcome, and mortality using logistic regression models adjusted for relevant confounders., Results: ICAC was present in 164 (84.5%) patients, with a median volume of 87.1 mm 3 (25th-75th quartile: 18.9-254.6 mm 3 ). We found that larger ICAC volumes were associated with incomplete arterial revascularization (adjusted odds ratio per unit increase in ln-transformed ICAC volume 0.73 [95% confidence interval, 0.57-0.93]) and with poorer functional outcome (adjusted odds ratio per unit increase in ln-transformed ICAC volume 1.31 [95% confidence interval, 1.04-1.66])., Conclusions: A larger amount of ICAC before mechanical thrombectomy in acute stroke patients is an indicator of worse postprocedural arterial revascularization and poorer functional outcome., (© 2016 American Heart Association, Inc.)

Introduction: Physical activity (PhA) prior to stroke has been associated with good outcomes after the ischemic insult, but there is scarce data on the involved molecular mechanisms., Methods: We studied consecutive acute ischemic stroke patients admitted to a single tertiary stroke center. Prestroke PhA was evaluated with the International Physical Activity Questionnaire (metabolic equivalent of minutes/week). We studied several circulating angiogenic and neurogenic factors at different time points: vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and brain-derived neurotrophic factor (BDNF) at admission, day 7, and at 3 months. We considered good functional outcome at 3 months (modified Rankin scale  ≤ 2) as primary end point, and final infarct volume as secondary outcome., Results: We studied 83 patients with at least 2 time point serum determinations (mean age 69.6 years, median National Institutes of Health Stroke Scale 17 at admission). Patients more physically active before stroke had a significantly higher increment of serum VEGF on the seventh day when compared to less active patients. This increment was an independent predictor of good functional outcome at 3 months and was associated with smaller infarct volume in multivariate analyses adjusted for relevant covariates. We did not find independent associations of G-CSF or BDNF levels neither with level of prestroke PhA nor with stroke outcomes., Conclusions: Although there are probably more molecular mechanisms by which PhA exerts its beneficial effects in stroke outcomes, our observation regarding the potential role of VEGF is plausible and in line with previous experimental studies. Further research in this field is needed., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of endovascular treatment on cognitive function as a prespecified secondary analysis of the REVASCAT (Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours) trial., Methods: REVASCAT randomized 206 patients with anterior circulation proximal arterial occlusion stroke to Solitaire thrombectomy or best medical treatment alone. Patients with established dementia were excluded from enrollment. Cognitive function was assessed in person with Trail Making Test (TMT) Parts A and B at 3 months and 1 year after randomization by an investigator masked to treatment allocation. Test completion within 5 minutes, time of completion (seconds), and number of errors were recorded., Results: From November 2012 to December 2014, 206 patients were enrolled in REVASCAT. TMT was assessed in 82 of 84 patients undergoing thrombectomy and 86 of 87 control patients alive at 3 months and in 71 of 79 patients undergoing thrombectomy and 72 of 78 control patients alive at 1 year. Rates of timely TMT-A completion were similar in both treatment arms, although patients undergoing thrombectomy required less time for TMT-A completion and had higher rates of error-free TMT-A performance. Thrombectomy was also associated with a higher probability of timely TMT-B completion (adjusted odds ratio 3.17, 95% confidence interval 1.51-6.66 at 3 months; and adjusted ratio 3.66, 95% confidence interval 1.60-8.35 at 1 year) and shorter time for TMT-B completion. Differences in TMT completion times between treatment arms were significant in patients with good functional outcome but not in those who were functionally dependent (modified Rankin Scale score >2). Poorer cognitive outcomes were significantly associated with larger infarct volume, higher modified Rankin Scale scores, and worse quality of life., Conclusions: Thrombectomy improves TMT performance after stroke, especially among patients who reach good functional recovery., Clinicaltrialsgov Identifier: NCT01692379., Classification of Evidence: This study provides Class I evidence that for patients with stroke from acute anterior circulation proximal arterial occlusion, thrombectomy improves performance on the TMT at 3 months., (© 2016 American Academy of Neurology.)

Vascular neuroimaging plays a decisive role in selecting the best therapy in patients with acute ischaemic stroke. However, compared with the arterial system, the role of veins has not been thoroughly studied. In this review, we present the major venous imaging-based biomarkers in ischaemic stroke. First, the presence of hypodense veins in the monophasic CT angiography ipsilateral to the arterial occlusion. Second, the asymmetry of venous drainage in the pathological cerebral hemisphere on CT and MRI dynamic angiography. Finally, the presence of hypodense veins on T2* -based MRI. From the physiological point of view, the venous imaging-based biomarkers would detect the alteration of brain perfusion (flow), as well as the optimisation of extraction oxygen mechanisms (misery perfusion). Several studies have correlated the venous imaging-based biomarkers with grade of collateral circulation, the ischaemic penumbra and clinical functional outcome. Although venous imaging-based biomarkers still have to be validated, growing evidence highlights a potential complementary role in the acute stroke clinical decision-making process., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background and Purpose: Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke., Methods: Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0-2), symptomatic intracerebral hemorrhage, and mortality., Results: The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0-3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29-5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups., Conclusions: Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups., (© 2016 The Authors.)

Background and Purpose: Contrary to usual static vascular imaging techniques, contrast-enhanced dynamic magnetic resonance angiography (dMRA) enables dynamic study of cerebral vessels. We evaluated dMRA ability to assess arterial occlusion, cerebral hemodynamics, and collateral circulation in acute ischemic stroke., Methods: Twenty-five acute ischemic stroke patients with proximal anterior circulation occlusion underwent dMRA on a 3T scanner within 12 hours of symptoms onset. Diffusion weighted imaging, Tmax6 s lesion volumes and hypoperfusion intensity ratio as volume of Tmax>6 s/volume of Tmax>10 s were measured. Site and grade of occlusion (Thrombolysis in Myocardial Infarction criteria) were evaluated on time-of-flight MRA and dMRA. Leptomeningeal collaterality (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [ASITN/SIR] Scale) and asymmetries in venous clearance were assessed exclusively on dMRA. Collateral filling was dichotomized into incomplete (ASITN/SIR 0-2) or complete (ASITN/SIR 3-4)., Results: On dMRA, site of occlusion was M1 in 21 patients, tandem internal carotid artery/M1 in 2 and tandem internal carotid artery/terminal internal carotid artery in 2 patients. Three tandem occlusions were not detected on time-of-flight-MRA. All patients had Thrombolysis in Myocardial Infarction 0 to 1 on time-of-flight-MRA, but three of them had Thrombolysis in Myocardial Infarction 2 on dMRA. Complete collateral filling (n=12, 48%) was associated with smaller diffusion weighted imaging lesion volume (P=0.039), smaller hypoperfused volume (P=0.018), and lower hypoperfusion intensity ratio (P=0.006). Patients with symmetrical clearance of transverse sinuses (52%) were more likely to have complete collateral filling (P=0.015)., Conclusions: As a fast, direct, feasible, noninvasive, and reliable method to assess site of occlusion, collateral circulation and hemodynamic alterations, dMRA provides profound insights in acute stroke., (© 2015 American Heart Association, Inc.)

Background: Metabolic syndrome (MetS) has been associated with higher resistance to clot lysis at 24 hours after tissue plasminogen activator (tPA) administration in patients with acute ischemic stroke. We aimed to test this hypothesis at earlier time points, when neurointerventional rescue procedures may still be indicated to achieve arterial recanalization., Methods: This is a prospective and observational study in consecutive stroke patients with MCA occlusion treated with IV tPA. MetS was diagnosed following the unified criteria of the last Joint Interim Statement 2009 participating several major organizations. The primary outcome variable was resistance to thrombolysis, defined as the absence of complete middle cerebral artery recanalization 2 hours after tPA bolus assessed by transcranial color-coded duplex or when rescue mechanical thrombectomy after IV tPA was required. Secondary outcome variables were dramatic neurological improvement (decrease in ≥10 points, or a National Institutes of Health Stroke Scale [NIHSS] score of 0-1 at 24 hours), symptomatic intracerebral hemorrhage following European-Australasian Acute Stroke Study II criteria, infarct volume at 24 hours (calculated by using the formula for irregular volumes, ABC/2), and good outcome (modified Rankin Scale score < 3) at 3 months., Results: A total of 234 patients (median baseline NIHSS score 16 [10-20]) were included and 146 (62.4%) fulfilled MetS criteria. After multivariate analysis, MetS emerged as an independent predictor of resistance to thrombolysis (odds ratio = 2.2 [1.3-4.2], P = .01) and absence of dramatic neurological improvement (odds ratio = .5 [.28-.97], P = .04). In addition, MetS conferred poorer functional outcome, higher symptomatic intracerebral hemorrhage rate, and increased infarct volume, although these associations disappeared after adjustment for covariates., Conclusions: MetS predicts patients with middle cerebral artery occlusion refractory to early clot dissolution after IV tPA. This finding may help in acute clinical decision-making., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The natural history of acute ischemic stroke (AIS) due to anterior circulation large artery occlusion is not well established. This information is essential for assessment of clinical benefit derived from recanalization therapies., Methods: Patients with AIS due to anterior circulation large artery occlusion not treated with reperfusion therapies admitted from January 2005 to September 2010 were consecutively selected. Site of occlusion was assessed with transcranial duplex according to Thrombolysis in Brain Infarction (TIBI) grades. Poor outcome was considered as a modified Rankin Scale>2 at 90 days., Results: A total of 120 patients were studied. Site of occlusion was terminal internal carotid artery (TICA) in 13 (10.8%), proximal middle cerebral artery (MCA) in 69 (57.5%), and distal MCA in 38 (31.7%) patients. Overall, 74.2% of patients had poor outcome. There were significant differences in poor outcome between patients with TICA, proximal MCA, and distal MCA occlusion (92%, 87%, 47%, P < .001) and mortality at 90 days (23%, 12%, 3%, P = .001)., Conclusions: Outcome of AIS patients with anterior circulation large artery occlusion not treated with reperfusion therapies is extremely poor in TICA and proximal MCA occlusions with better outcomes noted in distal MCA occlusions. These findings are relevant for estimation of treatment effect of reperfusion therapies according to occlusion location., (Copyright © 2013 by the American Society of Neuroimaging.)

Background and Purpose: We aimed to develop and validate a simple prehospital stroke scale to predict the presence of large vessel occlusion (LVO) in patients with acute stroke., Methods: The Rapid Arterial oCclusion Evaluation (RACE) scale was designed based on the National Institutes of Health Stroke Scale (NIHSS) items with a higher predictive value of LVO on a retrospective cohort of 654 patients with acute ischemic stroke: facial palsy (scored 0-2), arm motor function (0-2), leg motor function (0-2), gaze (0-1), and aphasia or agnosia (0-2). Thereafter, the RACE scale was validated prospectively in the field by trained medical emergency technicians in 357 consecutive patients transferred by Emergency Medical Services to our Comprehensive Stroke Center. Neurologists evaluated stroke severity at admission and LVO was diagnosed by transcranial duplex, computed tomography, or MR angiography. Receiver operating curve, sensitivity, specificity, and global accuracy of the RACE scale were analyzed to evaluate its predictive value for LVO., Results: In the prospective cohort, the RACE scale showed a strong correlation with NIHSS (r=0.76; P<0.001). LVO was detected in 76 of 357 patients (21%). Receiver operating curves showed a similar capacity to predict LVO of the RACE scale compared with the NIHSS (area under the curve 0.82 and 0.85, respectively). A RACE scale≥5 had sensitivity 0.85, specificity 0.68, positive predictive value 0.42, and negative predictive value 0.94 for detecting LVO., Conclusions: The RACE scale is a simple tool that can accurately assess stroke severity and identify patients with acute stroke with large artery occlusion at prehospital setting by medical emergency technicians.