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Introduction Thrombotic events are potentially devastating complications of coronavirus disease 2019 (COVID-19) infection. Although less common than venous thromboembolism, arterial thrombosis has been reported in COVID-19 cohorts in almost 3% of patients. We describe a patient with COVID-19 infection and concurrent cerebral and noncerebral infarction. Case report A 53-year-old man with history of COVID-19 pneumonia was admitted to a primary stroke center for speech disturbances and left hemiplegia. Urgent laboratory tests showed a great increase of inflammatory and coagulation parameters as D-dimer, ferritin, interleukin-6 and C-reactive protein. Neuroimaging found occlusion of the M1 segment of the right middle cerebral artery with early signs of ischemic stroke. He received intravenous thrombolysis and mechanical thrombectomy. Abdominal computed tomography discovered a splenic infarction with hemorrhagic transformation and bilateral renal infarction. Urgent angiography showed an associated splenic pseudoaneurysm, which was embolized without complications. He was treated with intermediate-dose anticoagulation (1 mg subcutaneous enoxaparin/kg/24 h), acetylsalicylic acid 100 mg and 5 days of intravenous corticosteroids. In the following days, inflammatory markers decreased so anticoagulant treatment was stopped and acetylsalicylic acid 300 mg was prescribed. His condition improved and he was discharged to a rehabilitation facility on hospital day 30. Conclusion In this case, a patient with multiple thrombotic events in the acute phase of COVID-19 infection, the delimitation of the inflammatory state through analytical markers as D-dimer helped to individualize the antithrombotic treatment (full anticoagulation or anticoagulation at intermediate doses plus antiplatelet treatment as used in our patient) and its duration. However, more data are needed to better understand the mechanisms and treatment of stroke in patients with COVID-19 infection.

BACKGROUND AND PURPOSE: The experience gained during the first COVID-19 wave could have mitigated the negative impact on stroke care in the following waves. Our aims were to analyze the characteristics and outcomes of patients with stroke admitted during the second COVID-19 wave and to evaluate the differences in the stroke care provision compared with the first wave. METHODS: This retrospective multicenter cohort study included consecutive stroke patients admitted to any of the seven hospitals with stroke units (SUs) and endovascular treatment facilities in the Madrid Health Region. The characteristics of the stroke patients with or without a COVID-19 diagnosis were compared and the organizational changes in stroke care between the first wave (25 February to 25 April 2020) and second wave (21 July to 21 November 2020) were analyzed. RESULTS: A total of 550 and 1191 stroke patients were admitted during the first and second COVID-19 waves, respectively, with an average daily admission rate of nine patients in both waves. During the second wave, there was a decrease in stroke severity (median National Institutes of Health Stroke Scale 5 vs. 6; p = 0.000), in-hospital strokes (3% vs. 8.1%) and in-hospital mortality (9.9% vs. 15.9%). Furthermore, fewer patients experienced concurrent COVID-19 (6.8% vs. 19.1%), and they presented milder COVID-19 and less severe strokes. Fewer hospitals reported a reduction in the number of SU beds or deployment of SU personnel to COVID-19 dedicated wards during the second wave. CONCLUSIONS: During the second COVID-19 wave, fewer stroke patients were diagnosed with COVID-19, and they had less stroke severity and milder COVID-19.

INTRODUCTION: The concurrency of both, acute stroke and acute myocardial infarction in normal conditions, outside the pandemic is rare. Coagulopathy has been associated with the inflammatory phase of coronavirus disease (COVID-19) and might be involved in this concurrency. CASES REPORT: We describe 2 patients with previous mild or no symptoms of COVID-19, admitted for acute stroke with recent/simultaneous myocardial infarction in whom admission polymerase chain reaction was negative but serologic testing diagnosed COVID-19. In these patients, concurrent stroke and myocardial infarction could have been promoted by COVID-19 infection. Management and evolution are detailed, and their contacts to confirm the COVID-19 infection. Pathogenic analysis of possible hypercoagulation state is described suggesting the hypothesis of endothelial dysfunction as the strongest mechanism involved in thrombus formation after the acute phase of COVID-19 infection. CONCLUSIONS: Our experience with these cases suggests that patients with mild symptoms can also present thromboembolic complications once the acute phase of COVID-19 infection has passed.

Introduction: Stroke is a serious health problem, given it is the second leading cause of death and a major cause of disability in the European Union. Our study aimed to assess the impact of stroke care organization measures (such as the development of stroke units, implementation of a regional stroke code, and treatment with intravenous thrombolysis and mechanical thrombectomy) implemented from 1997 to 2017 on hospital admissions due to stroke and mortality attributed to stroke in the Madrid health region. Methods: Epidemiological data were obtained from the National Statistics Institute public website. We collected data on the number of patients discharged with a diagnosis of stroke, in-hospital mortality due to stroke and the number of inhabitants in the Madrid health region each year. We calculated rates of discharges and mortality due to stroke and the number of inhabitants per SU bed, and we analysed temporal trends in in-hospital mortality due to stroke using the Daniels test in 2 separate time periods (before and after 2011). Figures representing annual changes in these data from 1997 to 2017 were elaborated, marking stroke care organizational measures in the year they were implemented to visualize their temporal relation with changes in stroke statistics. Results: Hospital discharges with a diagnosis of stroke have increased from 170.3/100,000 inhabitants in 1997 to 230.23/100,000 inhabitants in 2017. However, the in-hospital mortality rate due to stroke has decreased (from 33.3 to 15.2%). A statistically significant temporal trend towards a decrease in the mortality percentage and rate was found from 1997 to 2011. Conclusions: Our study illustrates how measures such as the development of stroke units, implementation of a regional stroke code and treatment with intravenous thrombolysis coincide in time with a reduction in in-hospital mortality due to stroke.

Background and purposeSpain has been heavily affected by COVID-19. Reallocation of resources for managing the outbreak might have caused a disruption in stroke care. This study analyses the impact on stroke care of reorganising the healthcare system in response to the first COVID-19 outbreak peak in Spain and the strategies adopted by Spanish stroke units to deal with this impact.Materials and methodsWe obtained data from a structured survey sent to the responsible of stroke units across the country. We recorded the number of strokes, stroke code activations, intravenous thrombolysis treatments and mechanical thrombectomies during February and March 2019 and 2020. We also collected information on the impact on workflow metrics and on the availability of specialised neurological care and rehabilitation treatments, the characteristics of stroke care for patients with SARS-CoV-2 infection and the impact on human resources. We compared the activity data between 2019 and 2020 and the information on activity and impact on stroke care between regions classified according to the disease incidence rate.ResultsFifty-seven (75%) of all stroke units in Spain responded to the survey. There was an overall reduction in admissions for all stroke types during the outbreak’s peak and in the number of stroke code activations and intravenous thrombolysis treatments, results that were independent of the COVID-19 incidence rate. Participants reported a delay in workflow metrics and a reduction of admissions to stroke units, outpatient clinics and rehabilitation therapies. Specific pathways and protocols for managing stroke patients with SARS-CoV-2 infection have been established.ConclusionThe COVID-19 outbreak has jeopardised all phases of stroke care. As a consequence, some patients with stroke did not receive adequate treatment.

Extracellular vesicles (EVs) are involved in intercellular signalling through the transfer of molecules during physiological and pathological conditions, such as ischaemic disease. EVs might therefore play a role in ischaemic stroke (IS) and myocardial infarction (MI). In the present study, we analysed the similarities and differences in the content of circulating EVs in patients with IS and MI. This prospective observational study enrolled 140 participants (81 patients with IS, 37 with MI and 22 healthy controls [HCs]). We analysed the protein and microRNA content from EVs using proteomics and reverse transcription quantitative real-time polymerase chain reaction and compared it between the groups. In the patients with IS and MI, we identified 14 common proteins. When comparing IS and MI, we found differences in the protein profiles (apolipoprotein B, alpha-2-macroglobulin, fibronectin). We also found lower levels of miR-340 and miR-424 and higher levels of miR-29b in the patients with IS and MI compared with the HCs. Lastly, we found higher miR-340 levels in IS than in MI. In conclusion, proteomic and miRNA analyses suggest a relationship between circulating EV content and the patient’s disease state. Although IS and MI affect different organs (brain and heart) with distinct histological characteristics, certain EV proteins and miRNAs appear to participate in both diseases, while others are present only in patients with IS., This work was sponsored by a grant from Miguel Servet (CP15/00069 to María Gutiérrez- Fernández), a predoctoral fellowship (FI17/00188 to Mari Carmen Gómez-de Frutos;FI18/00026 to Fernando Laso-García), a Sara Borrell postdoctoral fellowship (CD19/00033 to María Pérez-Mato), the INVICTUS PLUS network grant (RD16/0019/0005) from the Carlos III Health Institute Health Care Research Fund and was co-funded by the European Regional Development Fund (ERDF) and Juan de la Cierva postdoctoral fellowship (IJCI-2017-33505 to Laura Otero-Ortega, Spanish State Research Agency) and the Spanish Ministry of Science and Innovation.

A multidisciplinary panel of cardiologists, neurologists, internal medicine and specialists in haemostasis and thrombosis has elaborated this document showing recent scientific evidences supporting a better profile of direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKA), as well as the indications of specific antidotes and haemostatic agents to reverse the anticoagulant effects of DOACs. The analysis reinforces the best profile of DOACs and its special benefit in patients with basal high haemorrhagic risk.

Background and Purpose: The coronavirus disease 2019 (COVID-19) outbreak has added challenges to providing quality acute stroke care due to the reallocation of stroke resources to COVID-19. Case series suggest that patients with COVID-19 have more severe strokes; however, no large series have compared stroke outcomes with contemporary non–COVID-19 patients. Purpose was to analyze the impact of COVID-19 pandemic in stroke care and to evaluate stroke outcomes according to the diagnosis of COVID-19. Methods: Retrospective multicenter cohort study including consecutive acute stroke patients admitted to 7 stroke centers from February 25 to April 25, 2020 (first 2 months of the COVID-19 outbreak in Madrid). The quality of stroke care was measured by the number of admissions, recanalization treatments, and time metrics. The primary outcome was death or dependence at discharge. Results: A total of 550 acute stroke patients were admitted. A significant reduction in the number of admissions and secondary interhospital transfers was found. COVID-19 was confirmed in 105 (19.1%) patients, and a further 19 patients were managed as suspected COVID-19 (3.5%). No differences were found in the rates of reperfusion therapies in ischemic strokes (45.5% non–COVID-19, 35.7% confirmed COVID-19, and 40% suspected COVID-19; P =0.265). However, the COVID-19 group had longer median door-to-puncture time (110 versus 80 minutes), which was associated with the performance of chest computed tomography. Multivariate analysis confirmed poorer outcomes for confirmed or suspected COVID-19 (adjusted odds ratios, 2.05 [95% CI, 1.12–3.76] and 3.56 [95% CI, 1.15–11.05], respectively). Conclusions: This study confirms that patients with COVID-19 have more severe strokes and poorer outcomes despite similar acute management. A well-established stroke care network helps to diminish the impact of such an outbreak in stroke care, reducing secondary transfers and allowing maintenance of reperfusion therapies, with a minor impact on door-to-puncture times, which were longer in patients who underwent chest computed tomography.

Ultrasound is a noninvasive technique that provides real-time imaging with excellent resolution, and several studies demonstrated the potential of ultrasound in acute ischemic stroke monitoring. However, only a few studies were performed using animal models, of which many showed ultrasound to be a safe and effective tool also in therapeutic applications. The full potential of ultrasound application in experimental stroke is yet to be explored to further determine the limitations of this technique and to ensure the accuracy of translational research. This review covers the current status of ultrasound applied to monitoring and treatment in experimental animal models of stroke and examines the safety, limitations, and future perspectives., This research was funded by the Carlos III Health Institute Health Care Research Fund grant number FIS PI16/01052 and cofunded by the European Regional Development Fund (ERDF)–Miguel Servet (CP15/00069, CPII20/00002 to María Gutiérrez–Fernández; CP20/00024 to Laura Otero–Ortega) and predoctoral fellowship (FI17/00188 to Mari Carmen Gómez–de Frutos, FI18/00026 to Fernando Laso–García) and the INVICTUS PLUS Spanish Network (RD16/0019/0005) of the Carlos III Health Institute (ISCIII).

Background and Objective: Oral anticoagulation (OAC) for secondary stroke prevention is recommended in atrial fibrillation (AF) and other sources of cardioembolic stroke. Our objectives were to explore the differences in ischemic and hemorrhagic events when using OAC for secondary stroke prevention according to the type of anticoagulant treatment and to analyze the number and reasons for OAC switches during long-term follow-up. Methods: Ischemic stroke (IS) patients who were discharged on OAC for secondary stroke prevention from January 2014 to October 2017 were recruited in a prospective, multicenter, hospital-based registry. Follow-up at 3 months was scheduled at the outpatient clinic with subsequent annual phone interviews for 3 years. Patients were classified into three study groups according to OAC at discharge: Vitamin K antagonist (VKA), Factor Xa inhibitor (FXa), or direct thrombin inhibitor (DTI). We compared stroke recurrences, intracranial hemorrhage, major bleeding, and all-cause mortality during the follow-up. We recorded any switches in OAC and the main reasons for the change. Results: A total of 241 patients were included. An anticoagulant was indicated in the presence of a source of cardioembolic stroke in 240 patients (99.6%) and lupus plus antiphospholipid syndrome in one patient. Up to 86 patients (35.6%) were on OAC before the index stroke; in 71 (82.5%) of them, this was VKA. At hospital discharge, 105 were treated with FXa (43.8%), 96 with VKA (39.6%), and 40 with DTI (16.6%). The cumulative incidences at 3 years were 17% for stroke recurrence, 1.6% for intracranial hemorrhage, 4.9% for major hemorrhage, and 22.8% for all-cause mortality, with no differences among the OAC groups in any outcomes. During the follow-up, 40 OAC switches were recorded (63% of them to FXa), mostly due to stroke recurrence. Conclusion: Long-term OAC in secondary stroke prevention is associated with a lower frequency of bleeding complications than stroke recurrences. No differences between anticoagulant drugs were found in any of the analyzed outcomes. The main cause for OAC switch during follow-up was stroke recurrence., This study was supported by grants from the Foundation for Biomedical Research of La Paz University Hospital (PI 1131)

Introduction: The degree of disability after stroke needs to be objectively measured to implement adequate rehabilitation programs. Here, we evaluate the feasibility of a custom-built software to assess motor status after stroke.Methods: This is a prospective, case–control pilot study comparing stroke patients with healthy volunteers. A workout evaluation that included trunk and upper limb movement was captured with Kinect® and kinematic metrics were extracted with Akira®. Trunk and joint angles were analyzed and compared between cases and controls. Patients were evaluated within the first week from stroke onset using the National Institutes of Health Stroke Scale (NIHSS), Fulg-Meyer Assessment (FMA), and modified Rankin Scale (mRS) scales; the relationship with kinematic measurements was explored.Results: Thirty-seven patients and 33 controls were evaluated. Median (IQR) NIHSS of cases was 2 (0–4). The kinematic metrics that showed better discriminatory capacity were body sway during walking (less in cases than in controls, p = 0.01) and the drift in the forearm–trunk angle during shoulder abduction in supination (greater in cases than in controls, p = 0.01). The body sway during walking was moderately correlated with NIHSS score (Rho = −0.39; p = 0.01) but better correlated with mRS score (Rho = −0.52; p < 0.001) and was associated with the absence of disability (mRS 0–1) (OR = 0.64; p = 0.02). The drift in the forearm–trunk angle in supination was associated with the presence of disability (mRS >1) (OR = 1.27; p = 0.04).Conclusion: We present a new software that detects even mild motor impairment in stroke patients underestimated by clinical scales but with an impact on patient functionality.

Supplemental Digital Content is available in the text., Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institute of Health Stroke Scale was 10 (interquartile range [IQR], 4–18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institute of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4–18] versus 6 [IQR, 3–14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08–2.65] for higher National Institute of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2–6] versus 2 [IQR, 1–4], P

Acute ischemic stroke is currently a major cause of disability despite improvement in recanalization therapies. Stem cells represent a promising innovative strategy focused on reduction of neurologic sequelae by enhancement of brain plasticity. We performed a phase IIa, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Patients aged ≥60 years with moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] 8–20) were randomized (1:1) to receive intravenous adipose tissue–derived mesenchymal stem cells (AD-MSCs) or placebo within the first 2 weeks of stroke onset. The primary outcome was safety, evaluating adverse events (AEs), neurologic and systemic complications, and tumor development. The secondary outcome evaluated treatment efficacy by measuring modified Rankin Scale (mRS), NIHSS, infarct size, and blood biomarkers. We report the final trial results after 24 months of follow-up. Recruitment began in December 2014 and stopped in December 2017 after 19 of 20 planned patients were included. Six patients did not receive study treatment: two due to technical issues and four for acquiring exclusion criteria after randomization. The final study sample was composed of 13 patients (4 receiving AD-MSCs and 9 placebo). One patient in the placebo group died within the first week after study treatment delivery due to sepsis. Two non-treatment-related serious AEs occurred in the AD-MSC group and nine in the placebo group. The total number of AEs and systemic or neurologic complications was similar between the study groups. No injection-related AEs were registered, nor tumor development. At 24 months of follow-up, patients in the AD-MSC group showed a nonsignificantly lower median NIHSS score (interquartile range, 3 [3–5.5] vs 7 [0–8]). Neither treatment group had differences in mRS scores throughout follow-up visits up to month 24. Therefore, intravenous treatment with AD-MSCs within the first 2 weeks from ischemic stroke was safe at 24 months of follow-up.

Background and purposeTo investigate the efficacy and safety of mechanical thrombectomy in patients with acute ischemic stroke according to the oral anticoagulation medication taken at the time of stroke onset.Materials and methodsA retrospective multicenter study of prospectively collected data based on data from the registry the Madrid Stroke Network was performed. We included consecutive patients with acute ischemic stroke treated with mechanical thrombectomy and compared the frequency of intracranial hemorrhage and the modified Rankin Scale (mRS) score at 3 months according to anticoagulation status.ResultsThe study population comprised 502 patients, of whom 389 (77.5%) were not anticoagulated, 104 (20.7%) were taking vitamin K antagonists, and 9 (1.8%) were taking direct oral anticoagulants. Intravenous thrombolysis had been performed in 59.8% and 15.0% of non-anticoagulated and anticoagulated patients, respectively. Rates of intracranial hemorrhage after treatment were similar between non-anticoagulated and anticoagulated patients, as were rates of recanalization. After 3 months of follow-up, the mRS score was ≤2 in 56.3% and 55.7% of non-anticoagulated and anticoagulated patients, respectively (P=NS). Mortality rates were similar in the two groups (13.1%and12.4%, respectively). Among anticoagulated patients, no differences were found for intracranial bleeding, mRS score, or mortality rates between patients taking vitamin K antagonists and those taking direct oral anticoagulants.ConclusionsMechanical thrombectomy is feasible in anticoagulated patients with acute ischemic stroke. The outcomes and safety profile are similar to those of patients with no prior anticoagulation therapy.

BackgroundThe clinical consequences and factors related to the progression from a carotid near-occlusion (CNO) to a complete occlusion are not well established. Our aim is to describe the rate, predictive factors and clinical implications of the progression to complete carotid occlusion (PCCO) in a population of patients with symptomatic CNO.MethodsWe conducted a multicenter, nationwide, prospective study from January 2010 to May 2016. Patients with angiography-confirmed CNO were included. We collected information on demographic data, clinical manifestations, radiological and hemodynamic findings, and treatment modalities. A 24 month carotid-imaging follow-up of the CNO was performed.Results141 patients were included in the study, and carotid-imaging follow-up was performed in 122 patients. PCCO occurred in 40 patients (32.8%), and was more frequent in medically-treated patients (34 out of 61; 55.7%) compared with patients treated with revascularization (6 out of 61; 9.8%) (pConclusionsPCCO occurred within 24 months in more than half of the patients under medical treatment. Most episodes of PCCO were not associated with ipsilateral symptoms. Revascularization reduces the risk of PCCO.

Background and Purpose— Standardized registries may provide valuable data to further improve stroke care. Our aim was to obtain updated information about characteristics of stroke patients and management of stroke across the Ibero-American countries, using a common in-hospital registry (Safe Implementation of Treatments in Stroke–Sociedad Iberoamericana de Enfermedades Cerebrovasculares) as a basis for further quality improvement. Methods— Data for this study were entered into the Safe Implementation of Treatments in Stroke registry from September 2009 to December 2013 by 58 centers in 14 countries. Data included demographics, risk factors, onset-to-door time, National Institutes of Health Stroke Scale score, stroke subtype, ischemic stroke etiology, treatments, 3-month mortality, and modified Rankin Scale score. Time to treatment was also recorded for patients treated with thrombolysis. Results— Five thousand four hundred one patients were registered; median age, 65 years; 46% women; 3915 (72.5%) ischemic strokes; 686 (13.7%) hemorrhagic strokes; 213 (4.3%) subarachnoid hemorrhages; 414 (8.3%) transient ischemic attacks; and 31 (0.6%) cerebral vein thrombosis. The most prevalent risk factors were hypertension (71.3%), dyslipidemia (35.2%), and diabetes mellitus (23.6%). Atrial fibrillation was present in 15.1%. Three hundred one ischemic strokes were treated with intravenous thrombolysis (IVT; 7.7%). Patients undergoing IVT were more severely affected (median baseline National Institutes of Health Stroke Scale score, 11 versus 6). The rate of symptomatic intracerebral hemorrhages after IVT was 5.7%. At 3 months, 60.3% of IVT-treated patients and 59.1% of untreated patients were independent (modified Rankin Scale score, 0–2). Mortality was 11.4% in treated and 12.8% in untreated patients. Conclusions— Safe Implementation of Treatments in Stroke–Sociedad Iberoamericana de Enfermedades Cerebrovasculares is the largest registry of a general stroke population and the first study to evaluate the level of IVT use in Ibero-America. It provides valuable information that may help to improve the quality of stroke care in the Ibero-American region.

ObjectiveCurrent prehospital scales used to detect large vessel occlusion reveal very low endovascular thrombectomy (EVT) rates among selected patients. We developed a novel prehospital scale, the Madrid-Direct Referral to Endovascular Center (M-DIRECT), to identify EVT candidates for direct transfer to EVT-capable centers (EVT-Cs). The scale evaluated clinical examination, systolic blood pressure, and age. Since March 2017, patients closer to a stroke unit without EVT capabilities and an M-DIRECT positive score have been transferred to the nearest EVT-C. To test the performance of the scale-based routing protocol, we compared its outcomes with those of a simultaneous cohort of patients directly transferred to an EVT-C.MethodsIn this prospective observational study of consecutive patients with stroke code seen by emergency medical services, we compared diagnoses, treatments, and outcomes of patients who were closer to an EVT-C (mothership cohort) with those transferred according to the M-DIRECT score (M-DIRECT cohort).ResultsThe M-DIRECT cohort included 327 patients and the mothership cohort 214 patients. In the M-DIRECT cohort, 227 patients were negative and 100 were positive. Twenty-four (10.6%) patients required secondary transfer, leaving 124 (38%) patients from the M-DIRECT cohort admitted to an EVT-C. EVT rates were similar for patients with ischemic stroke in both cohorts (30.9% vs 31.5%). The M-DIRECT scale had 79% sensitivity, 82% specificity, and 53% positive predictive value for EVT. Recanalization and independence rates at 3 months did not differ between the cohorts.ConclusionsThe M-DIRECT scale was highly accurate for EVT, with treatment rates and outcomes similar to those of a mothership paradigm, thereby avoiding EVT-C overload with a low rate of secondary transfers.

Background and purpose The present study was conducted with the objective of evaluating the safety of primary mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke and comorbidities that preclude treatment with IV thrombolysis (IVT), compared with patients who received standard IVT treatment followed by MT. Secondary objectives were to analyse the recanalization rate and outcomes. Methods A prospective observational multicenter study (FUN-TPA) that recruited patients treated within 4.5 hours of symptom onset was performed. Treatments were IVT followed by MT if occlusion persisted, or primary MT when IVT was contraindicated. Outcome measures were procedural complications, symptomatic intracranial hemorrhage (SICH), recanalization rate, National Institutes of Health Stroke Scale (NIHSS) score at 7 days, modified Rankin Scale (mRS) score and mortality at 90 days. Results Of 131 patients, 21 (16%) had medical contraindications for IVT and were treated primarily with MT whereas 110 (84%) underwent IVT, followed by MT in 53 cases (40%). The recanalization rate and procedural complications were similar in the two groups. There were no SICHs after primary MT vs 3 (6%) after IVT+MT. Nine patients (43%) in the primary MT group achieved independence (mRS 0–2) compared with 36 (68%) in the IVT+MT group (p=0.046). Mortality rates in the two groups were 14% (n=3) vs 4% (n=2) (p=0.13). Adjusted ORs for independence in patients receiving standard IVT+MT vs MT in patients with medical contraindications for IVT were 2.8 (95% CI 0.99 to 7.98) and 0.24 (95% CI 0.04 to 1.52) for mortality. Conclusions MT is safe in patients with potential comorbidity-derived risks that preclude IVT. MT should be offered, aiming for prompt recanalization, to patients with LVO stroke unsuitable for IVT. Trial registration number NCT02164357; Results.

Background: Pre-clinical studies on adipose tissue-derived mesenchymal stem cells (AD-MSC) suggest its efficacy and safety for ischemic stroke (IS). Our aim was to evaluate the safety of a single dose of AD-MSC administered intravenously in acute IS patients. Methods: A phase II, randomised, double-blind, placebo-controlled, single-center, pilot clinical trial. We included patients aged ≥ 60 years, with moderate to severe IS. Patients were randomly assigned (1:1 ratio) to receive either 1M cells/kg AD-MSC or placebo within the first two weeks after the onset of an IS. The primary outcome measure was safety (adverse events, neurological and systemic complications, and tumor developments). Secondary outcomes explored efficacy (modified Rankin Scale (mRS) and NIHSS). Here we report the preliminary results at 6 months of follow-up. EudraCT: 2011-003551-18; NCT01678534. Findings: Recruitment was stopped in December 2017 after including 19 out of the 20 planned patients. Six patients did not receive the study treatment (3 for technical reasons and 3 because they presented exclusion criteria after randomisation). The final sample was composed of 13 patients (4 in the AD-MSC and 9 in the placebo group). One patient from the placebo group died within the first 7 days due to sepsis. Serious adverse events at 6 months were reported in 5.1% of the AD-MSC group and in 6.6% in the placebo group. No injection-related adverse events or tumour developments were reported. After 6 months of follow-up there were no significant differences between the groups in median NIHSS scores [2.5 (IQR 1.75, 3.50) vs. 5 (IQR 4.0, 7.50)] and median mRS [3 (IQR 3.0, 3.25) vs. 4 (IQR 3.0, 4.0)]. Interpretation: Intravenous administration of AD-MSC within the first 2 weeks from IS onset seems to be safe at 6-months of follow-up and shows a trend toward improving neurological and functional recovery. Trial Registration: The study was registered at Clinicaltrials.gov, under the number NCT01678534. Funding Statement: Spanish Ministry of Health (EC2010/171). Declaration of Interests: B Fuentes reports grants from Spanish Ministry of Health and European Commission (Horizon2020 program), during the conduct of the study; other from Daichi-Sankyo, other from Bayer, other from BMS-Pfizer, other from Novonordisk, other from Novartis, outside the submitted work; M Gutierrez-Fernandez rports grants from Spanish Ministry of Health and European Commission (Horizon2020 program), during the conduct of the study; non-financial support from Cellerix/Tigenix, non-financial support from Histocell, outside the submitted work.AM Borobia reports grants from Instituto de Salud Carlos III, during the conduct of the study; personal fees from Mundipharma, personal fees from Menarini, outside the submitted work; and Principal Investigator in Clinical Trials for GSK and Daiichi Sankyo. E Diez-Tejedor reports grants from Spanish Ministry of Health and European Commission (Horizon2020 program), during the conduct of the study; non-financial support from Cellerix/Tigenix, non-financial support from Histocell, other from Daichi-Sankyo, other from Bayer, other from Sanofy Aventis, other from Novartis outside the submitted work. R Gutierrez-Zuniga, M Alonso de Lecinana, JC Martinez Avila, G Ruiz-Ares, MC Gomez-de Frutos, F Laso-Garcia and L Otero-Ortega report nothing to disclosure. Ethics Approval Statement: It was approved by the La Paz University Hospital Research Ethics Committee and by the Spanish Agency of Medicines and Health Products (EudraCT: 2011-003551-18).

Objective The aim of the study was to illustrate the increased risk of ischemic stroke in the context of multiple myeloma (MM) under treatment with lenalidomide combined with dexamethasone. Methods This is a case report and literature review. Results A 62-year-old woman diagnosed with relapsed MM under treatment with lenalidomide and dexamethasone presented with acute onset disorientation, disturbed behavior, and aphasia. Cranial computed tomography scan revealed an acute cerebral infarction in the left middle cerebral artery territory, and brain magnetic resonance imaging showed additional silent ischemic lesions in other arterial territories. Common stroke etiologies were excluded after an extensive study, leading to a final diagnosis of cerebral infarction of uncommon cause probably related to MM and treatment with lenalidomide plus dexamethasone. A literature review provided 84 reports from the license holder, 2 more cases of stroke in patients with MM receiving lenalidomide and a recurrent stroke in a patient experiencing polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome) treated with lenalidomide. Conclusions Our case exemplifies the need to raise awareness about the risk of ischemic stroke associated with MM that might be increased by treatment with lenalidomide and to establish consistent recommendations regarding thromboprophylaxis to reduce comorbidities and mortality in these patients.

Motion capture systems (MCS) are used in neurological rehabilitation and for diagnosis of movement disorders. We aimed to explore the usefulness of MCS to obtain an objective measurement of functional status after stroke, especially in patients with minor or without deficit when measured by current motor clinical scales. Methods: Prospective observational case-control pilot study using Microsoft Kinect® analyzed with the software Akira®. Patients after acute stroke were included. All subjects performed the same exercises (standing, walking, sitting position, abduction of the upper limb in pronation and supination during 5 seconds each position and flexion of the upper limbs) that were recorded in a three-dimensional space. Joint angles and time of execution were registered and analyzed. The differences in execution between both sides of the body were compared between cases and controls. The relationship with the NIHSS score was analyzed with linear regression analysis and the mRS score with Pearson’s correlation coefficient (PCC). Results: 50 controls and 33 stroke patients were analyzed. The median NIHSS score was 2 (rank 0-12) and the median mRS was 0 (rank 0-4). The measurements that showed better discrimination capacity were those obtained from abduction of the upper limb: shift of the joint angles were different between cases and controls in the frontal plane for the elbow in pronation (p=0.01) and in supination (p< 0.001); and for the shoulder both in pronation and supination (p=0.01). These differences were independent of the NIHSS score, but were moderately correlated to the mRS score at the moment of the evaluation: elbow in pronation (PCC=0.48 IC=0.051-0.12) and in supination (PCC=0.61 IC=0.16-0.29); and shoulder in pronation (PCC=0.39 IC=0.02-0.08) and in supination (PCC=0.63 IC=0.13-0.25). Conclusion: Computational analysis of movement could be a useful tool for evaluation of upper limb function in stroke patients with slight deficit underestimated using current motor clinical scales and this is correlated with mRS. Further studies are needed to determine the better exercises to be considered and the relationship with functional outcome.

Background The risk of recurrent stroke among patients with symptomatic carotid near-occlusion is not well established, and management of the condition remains controversial. Symptomatic carotid near-occlusion with full collapse has been identified as a strong predictor of early recurrence. We aimed to analyze the 90-day risk of recurrent ipsilateral ischemic stroke in medically treated patients with symptomatic carotid near-occlusion. Methods We performed a multicenter, nationwide, prospective study from January 2010 to May 2016. Patients with angiography-confirmed symptomatic carotid near-occlusion were included. The primary endpoint was ipsilateral ischemic stroke or transient ischemic attack (TIA) within 90 days after the presenting event. For this analysis, patients who underwent revascularization within 90 days after stroke were excluded. Results The study population comprised 141 patients from 17 Spanish centers; 83 patients were treated medically. Primary endpoint occurred in eight patients, resulting in a cumulative rate of 10.6% (95% CI, 3.7–17.5). Previous history of stroke or transient ischemic attack was identified as an independent predictor for recurrence in the multivariate Cox regression analysis (HR, 4.37 [95% CI, 1.05–18.18]; p = 0.043), while the presence of full collapse was not associated with an increased risk (HR, 0.81 [95% CI, 0.17–3.92]; p = 0.793). The risk of recurrence was also not affected by the presence of significant stenosis or occlusion of the contralateral carotid artery, or by the collateral circulation. Conclusions Patients with symptomatic carotid near-occlusion seem to have an increased risk of early ipsilateral recurrent stroke. Our results contrast with the low risk of symptomatic carotid near-occlusion reported to date. Full collapse did not increase the risk of recurrent stroke in our study.

Background and purposeThe benefits of mechanical thrombectomy (MT) in basilar artery occlusions (BAO) have not been explored in recent clinical trials. We compared outcomes and procedural complications of MT in BAO with anterior circulation occlusions.MethodsData from the Madrid Stroke Network multicenter prospective registry were analyzed, including baseline characteristics, procedure times, procedural complications, symptomatic intracranial hemorrhage (SICH), modified Rankin Scale (mRS), and mortality at 3 months.ResultsOf 479 patients treated with MT, 52 (11%) had BAO. The onset to reperfusion time lapse was longer in patients with BAO (median (IQR) 385 min (320–540) vs 315 min (240–415), pConclusionsMT is more laborious and shows more procedural complications in BAO than in anterior circulation strokes. The likelihood of futile recanalization is higher in BAO and is associated with greater age and longer procedure duration. A refinement of endovascular procedures for BAO might help optimize the results.

Use of thrombolysis in acute ischaemic stroke may be limited by a narrow benefit/risk ratio. Pharmacological inhibition of the ischaemic cascade may constitute an effective and safer approach to stroke treatment. This study compared the effects of high doses of cytidine diphosphate-choline (CDP-choline; 1000 mg/kg) with recombinant tissue plasminogen activator (rt-PA; 5 mg/kg) in an experimental animal model of embolic stroke. Fifteen rats were embolized in the right internal carotid artery with an autologous clot and were divided into three groups: (1) infarct; (2) intravenous rt-PA 5 mg/kg 30 minutes post-embolization; and (3) CDP-choline 1000 mg/kg, intraperitoneal, three doses, 30 minutes, 24 hours, and 48 hours post-embolization. Functional evaluation scores were evaluated using Rogers test, lesion volume by haematoxylin and eosin staining, cell death with transferase-mediated dUTP nick-end labelling, and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha with enzyme-linked immunosorbent assay. In this study, CDP-choline and rt-PA produced a significant reduction in brain damage considering infarct volume, cell death, and inflammatory cytokines (tumour necrosis factor-alpha and IL-6) compared with the infarct group. Additionally, CDP-choline significantly decreased infarct volume, cell death, and IL-6 levels with respect to the rt-PA group. From these results, we conclude that high-dose CDP-choline may be an effective treatment for acute ischaemic stroke even in absence of thrombolysis.

Background: Patients who present with symptoms mimicking ischaemic stroke (IS), but have a different diagnosis, are known as stroke mimics (SM). The necessity for rapid administration of intravenous thrombolysis in patients with acute IS may lead to treatment of patients with conditions mimicking stroke. A variable proportion of patients with SM (1.4–14%) are currently treated with intravenous tissue plasminogen activator therapy (IV-tPA). The outcome of these patients is generally favourable and complications are rather infrequent. We aimed to determine the frequency, clinical features and prognosis of SM patients treated with IV-tPA in an experienced stroke centre. Methods: A prospective registry was assembled with patients treated with IV-tPA at our stroke unit from January 2004 to December 2011. We recorded age, gender, baseline National Institutes of Health Stroke Scale (NIHSS) score, treatment delay, vascular risk factors, clinical syndrome and aetiology. We retrospectively analysed the clinical characteristics of SM, safety (symptomatic intracranial haemorrhage and mortality) and outcome measures (modified Rankin Scale at 3 months, mRS) and compared them with IS patients. Results: 621 patients were treated with IV-tPA during the study period, 606 (97.5%) were IS and 15 (2.4%) were SM. The aetiology of SM was somatoform disorders (5), headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome (3), herpetic encephalitis (2), glial tumours (2), and migraine with aura, focal seizure and cortical vein thrombosis in single cases. SM were younger (72 ± 14 vs. 53.7 ± 16 years, p < 0.05), had a lower baseline deficit [NIHSS 13 (9–18) vs. 8 (5–10), p < 0.05], fewer vascular risk factors, and left hemisphere symptoms were predominant (80 vs. 52.4%, p < 0.05). Global aphasia without hemiparesis (GAWH) was the presenting symptom in 8 (54%) SM and 44 (7%) IS (p < 0.05). Multimodal computed tomography was performed in 3 SM patients and showed perfusion deficits in 2 of them. No intracranial haemorrhage or disability (functional outcome at 3 months, mRS >2) was recorded in any SM patient. Conclusions: The use of intravenous thrombolysis appears to be safe in our SM patients, and prognosis is universally favourable. Somatoform disorder and HaNDL syndrome were prominent causes, and GAWH the most common presentation. The safety of thrombolysis in SM suggests that delaying or withholding treatment may be inappropriate: the benefit of thrombolysis in case of IS may outweigh the risks of treating an SM. Further studies may assess the future role of multimodal computed tomography in the differential diagnosis between IS and SM.

Background and aim Safety and efficacy of intravenous thrombolysis in stroke patients with recent transient ischemic attack are hotly debated. Patients suffering transient ischemic attack may present with diffusion-weighted imaging lesions, and although normal computed tomography would not preclude thrombolysis, the concern is that they may be at higher risk for hemorrhage ***post-thrombolysis treatment. Prior ipsilateral transient ischemic attack might provide protection due to ischemic preconditioning. We assessed post-thrombolysis outcomes in stroke patients who had prior transient ischemic attack. Methods Multicentered prospective study of consecutive acute stroke patients treated with intravenous tissue plasminogen activator (tPA). Ipsilateral transient ischemic attack, baseline characteristics, risk factors, etiology, and time-lapse to treatment were recorded. National Institutes of Health Stroke Scale at seven-days and modified Rankin Scale at three-months, symptomatic intracranial hemorrhage, and mortality were compared in patients with and without transient ischemic attack. Results There were 877 patients included, 60 (6.84%) had previous ipsilateral transient ischemic attack within ***one-month prior to the current stroke (65% in the previous 24 h). Transient ischemic attack patients were more frequently men (70% vs. 53%; P = 0.011), younger (63 vs. 71 years of age; P = 0.011), smokers (37% vs. 25%; P = 0.043), and with large vessel disease (40% vs. 25%; P = 0.011). Severity of stroke at onset was similar to those with and without prior transient ischemic attack (median National Institutes of Health Stroke Scale score 12 vs. 14 P = 0.134). Those with previous transient ischemic attack were treated earlier (117 $pL 52 vs. 144 $pL 38 mins; P #< 0.005). After adjustment for confounding variables, regression analysis showed that previous transient ischemic attack was not associated with differences in stroke outcome such as independence (modified Rankin Scale 0–2) (odds ratios: 1.035 (0.57–1.93) P = 0.91), mortality (odds ratios: 0.99 (0.37–2.67) P = 0.99), or symptomatic intracranial hemorrhage (odds ratios: 2.04 (0.45–9.32) P = 0.36). Conclusions Transient ischemic attack preceding ischemic stroke does not appear to have a major influence on outcomes following thrombolysis. Patients with prior ipsilateral transient ischemic attack appear not to be at higher risk of bleeding complications.

Objective To study the influence of polyvascular atherothrombotic disease on stroke patient prognosis, its relation with inflammatory markers, and to analyze the progression of atherothrombotic disease. Methods MITICO is a multi-centered prospective observational study recruiting non-anticoagulated ischemic stroke patients. Blood samples were obtained at baseline and at one year follow-up for determination of high sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (c-Fn). Patients with polyvascular atherothrombotic disease were considered when presented a history of angina–myocardial infarction, intermittent claudication or ischemic limbs-amputation at inclusion. Results The sample consisted of 863 patients, 121 of them considered as polyvascular atherothrombotic disease (14.02%). Recurrence and vascular death were higher in patients with polyvascular atherothrombotic disease, as compared to patients with monovascular atherothrombotic disease (19.8% vs. 12.4%, p =0.022). Baseline plasma levels of IL-6 and VCAM-1 were higher in patients with polyvascular atherothrombotic disease. IL-6 and VCAM-1 levels were independently associated with a new vascular episode/vascular death. This association was stronger in the group of patients with polyvascular atherothrombotic disease. Baseline levels of IL-6, VCAM-1 and c-Fn were significantly higher in patients who developed progression of atherothrombotic disease. The increase from baseline in MMP-9 and c-Fn levels after one year follow-up was associated to progression of atherothrombotic disease. Conclusions Stroke patients with polyvascular atherothrombotic disease showed higher rates of vascular recurrence and a stronger association with inflammatory markers. Progression of atherothrombotic disease was associated with inflammatory markers.

Background: Stroke risk is increased in AIDS patients, and highly active antiretroviral therapy (HAART) may accelerate atherosclerosis, but little is known about the incidence and risk factors for ischemic stroke in patients under HAART. We have studied the incidence, types of stroke and possible risk factors for cerebrovascular ischemic events in a large cohort of HIV-1-infected patients treated with HAART. Methods: We conducted a retrospective review of ischemic strokes and transient ischemic attacks occurring in a cohort of HIV-1-infected patients treated with HAART from 1996 to 2008. As a control group, consecutive unselected patients from the same cohort were included. Patients and controls were compared for demographic, clinical and laboratory variables, including vascular risk factors, data on HIV infection and duration of HAART. Variables with significant differences were included in a backward logistic regression model. Results: Twenty-seven cerebrovascular ischemic events occurred in 25 patients, with an incidence of 189 events (166 strokes) per 100,000 patients/year. Independent factors associated with cerebrovascular events were: history of high alcohol intake (OR 7.13, 95% CI 1.69–30.11; p = 0.007), a previous diagnosis of AIDS (OR 6.61, 95% CI 2.03–21.51; p = 0.002) and fewer months under HAART (OR 0.97, 95% CI 0.96–0.99; p < 0.001). Six patients (24%) had large artery atherosclerosis: they had a similar HAART duration to controls. Conclusions: Stroke incidence is high in patients with HIV-1 infection treated with HAART. Duration of HAART exerted a global protective effect for cerebrovascular ischemic events, and our results do not support a major role in large artery atherosclerosis stroke. High alcohol intake is a major risk factor for stroke in these patients.

Stroke is a neurological emergency. The early administration of specific treatment improves the prognosis of the patients. Emergency care systems with early warning for the hospital regarding patients who are candidates for this treatment (stroke code) increases the number of patients treated. Currently, reperfusion via thrombolysis for ischemic stroke and attention in stroke units are the bases of treatment. Healthcare professionals and health provision authorities need to work together to organize systems that ensure continuous quality care for the patients during the whole process of their disease. To implement this, there needs to be an appropriate analysis of the requirements and resources with the objective of their adjustment for efficient use. It is necessary to provide adequate information and continuous training for all professionals who are involved in stroke care, including primary care physicians, extrahospital emergency teams and all physicians involved in the care of stroke patients within the hospital. The neurologist has the function of coordinating the protocols of intrahospital care. These organizational plans should also take into account the process beyond the acute phase, to ensure the appropriate application of measures of secondary prevention, rehabilitation, and chronic care of the patients that remain in a dependent state. We describe here the stroke care program in the Community of Madrid (Spain).

The final publication is available at Springer via http://dx.doi.org/10.1007/s00234-016-1652-7, Introduction Reliable predictors of poor clinical outcome despite successful revascularization might help select patients with acute ischemic stroke for thrombectomy. We sought to determine whether baseline Alberta Stroke Program Early CT Score (ASPECTS) applied to CT angiography source images (CTA-SI) is useful in predicting futile recanalization. Methods Data are from the FUN-TPA study registry (ClinicalTrials.gov; NCT02164357) including patients with acute ischemic stroke due to proximal arterial occlusion in anterior circulation, undergoing reperfusion therapies. Baseline non-contrast CT and CTA-SI-ASPECTS, timelapse to image acquisition, occurrence, and timing of recanalization were recorded. Outcome measures were NIHSS at 24 h, symptomatic intracranial hemorrhage, modified Rankin scale score, and mortality at 90 days. Futile recanalization was defined when successful recanalization was associated with poor functional outcome (death or disability). Results Included were 110 patients, baseline NIHSS 17 (IQR 12; 20), treated with intravenous thrombolysis (IVT; 45 %), primary mechanical thrombectomy (MT; 16 %), or combined IVT+MT (39 %). Recanalization rate was 71 %, median delay of 287 min (225; 357). Recanalization was futile in 28 % of cases. In an adjusted model, baseline CTA-SI-ASPECTS was inversely related to the odds of futile recanalization (OR 0.5; 95 % CI 0.3–0.7), whereas NCCT-ASPECTS was not (OR 0.8; 95 % CI 0.5–1.2). A score ≤5 in CTA-SIASPECTS was the best cut-off to predict futile recanalization (sensitivity 35 %; specificity 97 %; positive predictive value 86 %; negative predictive value 77 %). Conclusions CTA-SI-ASPECTS strongly predicts futile recanalization and could be a valuable tool for treatment decisions regarding the indication of revascularization therapies

Stroke constitutes a serious socioeconomic and health care problem in women because it is the principal cause of incapacity and the first cause of death in this section of the population in several countries. The incidence of cerebral infarction and myocardial infarction is lower in females than in males, but only up to menopause, when, especially after >65 years of age, the differences disappear. This is attributable to the protective role of the natural estrogens during the fertile part of the woman’s life. The estrogens have antiatherogenic and neuroprotective effects and, before menopause, account for a risk profile that is less atherogenic. The risk factors that have higher importance in young women are migraine and oral contraceptive use as well as etiologies specifically associated with pregnancy, birth and puerperium, or even diseases that present more commonly in women (systemic lupus erythematosus, fibromuscular dysplasia). These entities lose their relevance after menopause, when the classical vascular-disease risk factors take on their role, and also include others such as hormone replacement therapy. Due to the specific epidemiology of stroke, females are underrepresented in the clinical trials of primary and secondary prevention, the result being that the outcomes measured in these trials are less consistent and do not show as clear a benefit for women as for men.

It has been debated whether the penumbral pattern, as identified using multimodal imaging, is a specific marker of tissue viability in ischemic stroke. We assessed whether perfusion computed tomography (PCT) accurately identifies salvageable tissue and helps predict postreperfusion outcomes.A retrospective study of patients with anterior circulation stroke undergoing reperfusion therapies who had a PCT before treatment and an assessment of vessel recanalization post treatment was conducted. Tissue at risk was considered as that with reduced cerebral blood flow, whereas the infarct core was the region of reduced cerebral blood volume, the mismatch region being salvageable tissue. The volume of hypodensity in slices corresponding to perfusion acquisition cage in 24-hour computed tomography (partial lesion volume [PLV]) was measured. Outcome variables were the amount of preserved tissue, that is, the difference between volumes of tissue at risk and PLV expressed as a percentage, and the modified Rankin Scale (mRS) score at 3 months.Patients (n = 34) meeting the inclusion criteria were included. Vessel recanalization was associated with a larger amount of tissue at risk preserved from definite lesion (89% [interquartile range {IQR}: 76-94] versus 46% [IQR: 23-86], P .005). The amount of preserved tissue correlated with clinical outcome at 24 hours: for each 10% of preserved tissue, the National Institutes of Health Stroke Scale score improved by 3 points (95% confidence interval [CI]: -4.9 to -.8, P = .007) and was the only predictor of independency (mRS score 0-2) following adjustment for covariates (odds ratio 1.15, 95% CI: 1.04-1.28, P = .005).PCT provides accurate markers of viability of tissue in acute ischemic stroke and could help predict the degree of improvement following reperfusion.

Background and Purpose— The complexity of endovascular revascularization treatment (ERT) in acute ischemic stroke and the small number of patients eligible for treatment justify the development of stroke center networks with interhospital patient transfers. However, this approach might result in futile transfers (ie, the transfer of patients who ultimately do not undergo ERT). Our aim was to analyze the frequency of these futile transfers and the reasons for discarding ERT and to identify the possible associated factors. Methods— We analyzed an observational prospective ERT registry from a stroke collaboration ERT network consisting of 3 hospitals. There were interhospital transfers from the first attending hospital to the on-call ERT center for the patients for whom this therapy was indicated, either primarily or after intravenous thrombolysis (drip and shift). Results— The ERT protocol was activated for 199 patients, 129 of whom underwent ERT (64.8%). A total of 120 (60.3%) patients required a hospital transfer, 50 of whom (41%) ultimately did not undergo ERT. There were no differences in their baseline characteristics, the times from stroke onset, or in the delays in interhospital transfers between the transferred patients who were treated and those who were not treated. The main reasons for rejecting ERT after the interhospital transfer were clinical improvement/arterial recanalization (48%) and neuroimaging criteria (32%). Conclusions— Forty-one percent of the ERT transfers were futile, but none of the baseline patient characteristics predicted this result. Futility could be reduced if repetition of unnecessary diagnostic tests was avoided.

An approach combining reperfusion mediated by thrombolytics with pharmacological neuroprotection aimed at inhibiting the physiopathological disorders responsible for ischemia-reperfusion damage, could provide an optimal treatment of ischemic stroke. We investigate, in a rat embolic stroke model, the combination of rtPA with citicoline as compared to either alone as monotherapy, and whether the neuroprotector should be provided before or after thrombolysis to achieve a greater reduction of ischemic brain damage. One hundred and nine rats have been studied: four were sham-operated and the rest embolized in the right internal carotid artery with an autologous clot and divided among 5 groups: 1) control; 2) iv rtPA 5 mg/kg 30 min post-embolization 3) citicoline 250 mg/kg ip x3 doses, 10 min, 24 h and 48 h post-embolization; 4) citicoline combined with rtPA following the same pattern; 5) rtPA combined with citicoline, with a first dose 10 min after thrombolysis. Mortality, neurological score, volume of ischemic lesion and neuronal death (TUNEL) after 72 h and plasma levels of IL-6 and TNF-alpha, were considered to assess ischemic brain damage. Compared with controls, the use of citicoline after thrombolysis produced the greatest reduction of mortality caused by the ischemic lesion (p

Background and Purpose. Intravenous thrombolysis using tissue plasminogen activator is safe and probably effective in patients >80 years old. Nevertheless, its safety has not been specifically addressed for the oldest old patients (≥85 years old, OO). We assessed the safety and effectiveness of thrombolysis in this group of age. Methods. A prospective registry of patients treated with intravenous thrombolysis. Patients were divided in two groups (, This work is part of the Spanish collaborative research network RENEVAS (Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, RD06/0026/008, RD07/0026/2003)

Background Small clinical series have reported the safety of intravenous thrombolysis in ischemic stroke related to extracranial internal carotid dissection. However, no studies specifically analyzing the effects on stroke outcome are available. Aims Our goal was to evaluate whether patients with ischemic stroke related to extracranial internal carotid dissection obtain any benefit from intravenous thrombolysis. Methods Multicenter, prospective and observational study conducted in four university hospitals from the Madrid Stroke Network. Consecutive ischemic stroke patients who received intravenous thrombolysis were included, as well as patients with extracranial internal carotid dissection regardless of intravenous thrombolysis treatment. Stroke severity (NIHSS) and three-month outcome (modified Rankin Scale) were compared between the following groups: ( 1 ) intravenous thrombolysis-treated patients with ischemic stroke related to extracranial internal carotid dissection vs. other causes of stroke; ( 2 ) intravenous thrombolysis-treated extracranial internal carotid dissection patients vs. nonintravenous thrombolysis treated. Outcome was rated at three-months using the modified Rankin Scale. A good outcome was defined as a modified Rankin Scale score ≤2. Results A total of 625 intravenous thrombolysis-treated patients were included; 16 (2·56%) had extracranial internal carotid dissection. Besides, 27 patients with extracranial internal carotid dissection and ischemic stroke who did not receive intravenous thrombolysis were also included. As compared with other etiologies, patients with extracranial internal carotid dissection were younger, had similar stroke severity and showed less improvement in their NIHSS score at Day 7 (1·38; (95% CI −3·77 to 6·54) vs. 6·81; (95% CI −5·99 to 7·63) P=0·004), but without differences in good outcomes at three-months (43·8% vs. 58·2%; NS). Extracranial internal carotid dissection intravenous thrombolysis-treated patients had more severe strokes at admission than those who were nonintravenous thrombolysis treated (median NIHSS: 15 vs. 7; P=0·031). Intravenous thrombolysis was safe in extracranial internal carotid dissection with no symptomatic hemorrhagic events; however, without differences in good outcome compared with the natural course of extracranial internal carotid dissection (nonintravenous thrombolysis treated) after adjustment for stroke severity (46·7% vs. 64·3%; NS). Conclusions As compared with other etiologies, stroke due to extracranial internal carotid dissection seems to obtain similar benefits from intravenous thrombolysis in outcome at three-months. Although intravenous thrombolysis is safe in stroke attributable to extracranial internal carotid dissection, no differences in outcome were found when comparing intravenous thrombolysis treated with nonintravenous thrombolysis-treated patients, even after adjustment for stroke severity.

Background: Information is scare regarding the safety of intravenous thrombolysis in patients under anticoagulant treatment, given that this is an exclusion criterion in clinical trials. We analyzed the risk of hemorrhagic complications following thrombolysis in patients under treatment with low-molecular-weight heparins (LMWH) and oral anticoagulants (OA). Methods: In a multicentered prospective study of consecutive acute stroke patients treated with intravenous alteplase we recorded age, gender, baseline NIHSS score, treatment delay, risk factors, etiology and previous therapy. The neurological progress (National Institutes of Health Stroke Scale at 7 days) and functional evolution at 3 months (modified Rankin Scale score), mortality and symptomatic intracerebral hemorrhage (SICH) were compared between patients with LMWH or OA and those without prior anticoagulant therapy. Results: Of the 1,482 patients, 21 (1.4%) had received LMWH and 70 (4.7%) OA (international normalized ratio, INR, 0.9-2.0). Patients on OA were older, presented higher basal glucose levels, had been treated later and had a higher prevalence of hypertension, dyslipidemia, prior stroke, atrial fibrillation and cardioembolic pathologies. The severity of stroke on admission was similar in the different groups. The percentages of patients achieving independence (mRS 0-2) at 3 months were 33, 44 and 58 (LMWH, OA and no prior anticoagulant treatment, respectively; p = 0.02 for both comparisons of LMWH vs. no treatment and OA vs. no treatment); the mortality rates were 30, 25 and 12% (p = 0.010, p = 0.001, respectively) and the SICH were 14, 3 and 2% (p < 0.0001 for comparison of LMWH vs. no treatment). In the case of treatment with OA, the outcomes were independent of the INR value. Following adjustment for confounding variables, the prior use of OA was associated with higher mortality (OR: 2.15, 95% CI: 1.1-4.2; p = 0.026) but not with SICH transformation or lower probability of independence. The use of LMWH was associated with higher mortality (OR: 5.3, 95% CI: 1.8-15.5; p = 0.002), risk of SICH (OR: 8.4, 95% CI: 2.2-32.2; p = 0.002) and lower probability of achieving independence (OR: 0.3, 95% CI: 0.1-0.97; p = 0.043). Conclusions: The use of intravenous thrombolysis appears to be safe in patients previously treated with OA with INR levels

Patients admitted to Cardiology and Cardiac Surgery Departments have an increased risk of ischemic stroke (IS). We analyzed clinical characteristics, quality of neurological care and mortality of in-hospital strokes (IHS) in these departments.Prospective registry of in-hospital ISs in Cardiology and Cardiac Surgery in 13 Spanish hospitals during 2008. Demographic, clinical and therapeutic data as well as mortality and functional evolution were recorded.73 patients were included. Mean age was 72±11.6 years. 75.4% of IS were cardioembolic. Special risk factors were presence of cardiac sources of embolism (86.3%), prior withdrawal of antithrombotic treatment (22%) and invasive procedures (65.7%). First neurological assessment was done in the first 3hours in 49.5% and beyond 24hours from IS onset in 20.5%. Ten patients were treated with intravenous thrombolysis, which was not possible in 8 patients because of the delay in calling the neurologist. Most frequent reasons for exclusion from thrombolytic therapy were recent major surgical procedures (33.3%) and anticoagulant therapy (38%). Three-month mortality was 15% and only 53.7% were functionally independent. Patients treated with thrombolysis had a better evolution (87.5% of independent patients, p=0.04).IS in Cardiology and Cardiac Surgery are mostly cardioembolic strokes and produce a high proportion of dependent patients. Patients treated with thrombolysis had a better evolution. Delays in contacting the neurologist led to exclusion from treatment an important proportion of patients who met thrombolysis criteria.

Background and Purpose— In-hospital strokes (IHSs) are potential candidates for thrombolysis. We analyzed the treatment procedures, safety, and efficacy of intravenous tissue plasminogen activator (IV-tPA) in IHSs compared with out-of-hospital strokes (OHSs). Methods— This study was based on a multicenter prospective registry of patients treated with IV-tPA divided into IHSs and OHSs. We recorded intrahospital delays and stroke outcomes. Results— Among 367 patients treated with IV-tPA, 30 were IHSs. Baseline characteristics were similar except for a greater proportion of diabetes (36.7% vs 17.5%, P =0.01), cardiac failure (16.7% vs 5.3%, P =0.014), and atrial fibrillation (33.3% vs 17.5%, P =0.034) in IHSs than OHSs. In-hospital delays were significantly longer in IHSs for door-to-computed tomography time (39.5±18.7 vs 22.6±19.7 minutes, P P Conclusions— In-hospital procedures for thrombolysis proceed more slowly in IHSs than in OHSs. Thrombolysis is safe and efficient in IHS.

Estrogens have proven vasoprotective properties against atherosclerosis that depend on the direct effect on vascular smooth muscle and endothelium and on systemic actions that imply serum lipids, coagulation and fibrinolytic cascades, vasoactive proteins and antioxidant systems. They also have neuroprotective effects against cerebral ischemia that include antioxidant and anti-inflammatory effects, modulation of protein synthesis, inhibition of apoptosis and trophic effects and preservation of microvascular blood flow in the ischemic area. Estrogenic actions depend on activation of specific estrogen receptors that modulate gene expression and produce long-term effects on vascular endothelial and smooth muscle cells, neurons and glia, on interaction with plasma membrane sites that produce rapid non-genomic actions and also on receptor-independent mechanisms. This paper reviews what it is known about the mechanisms underlying the vaso- and neuroprotective effects of estrogens. Experimental and clinical evidences of such protective effects are also discussed. Therapeutical implications for stroke prevention and treatment derived from the available evidence are considered.

Undeniable advances have been made in clinical and experimental investigation into the pathophysiology, diagnosis, and treatment of cerebral ischemia. However, with the exception of intravenous thrombolysis and some neuroprotectors, such as citicoline, the majority of the drugs successfully tested in experimental studies have failed in clinical trials. Valuable lessons for the improvement of research methodology and appropriate coordination of experimental and clinical research can be learnt from the analysis of discrepancies between the laboratory and clinic, which will allow us to increase the power and cost-effectiveness of the studies. In addition, this progress has opened the way for the investigation of very promising new therapeutic strategies, such as combined pharmacological and mechanical thrombolysis, thrombolysis and neuroprotection, or the combination of various neuroprotectors, antiapoptotic therapies, and neurorestoration therapies, such as stem cell transplants.

Background our objective was to examine the plasma levels of three biological markers involved in cerebral ischemia (IL-6, glutamate and TNF-alpha) in stroke patients and compare them with two different rat models of focal ischemia (embolic stroke model- ES and permanent middle cerebral artery occlusion ligation model-pMCAO) to evaluate which model is most similar to humans. Secondary objectives: 1) to analyze the relationship of these biological markers with the severity, volume and outcome of the brain infarction in humans and the two stroke models; and 2) to study whether the three biomarkers are also increased in response to damage in organs other than the central nervous system, both in humans and in rats. Methods Multi-center, prospective, case-control study including acute stroke patients (n = 58) and controls (n = 19) with acute non-neurological diseases Main variables: plasma biomarker levels on admission and at 72 h; stroke severity (NIHSS scale) and clinical severity (APACHE II scale); stroke volume; functional status at 3 months (modified Rankin Scale [mRS] and Barthel index [BI]). Experimental groups: ES (n = 10), pMCAO (n = 6) and controls (tissue stress by leg compression) (n = 6). Main variables: plasma biomarker levels at 3 and 72 h; volume of ischemic lesion (H&E) and cell death (TUNEL). Results in stroke patients, IL-6 correlated significantly with clinical severity (APACHE II scale), stroke severity (NIHSS scale), infarct volume (cm3) and clinical outcome (mRS) (r = 0.326, 0.497, 0.290 and 0.444 respectively; P