Publications by authors named "Valeria Caso"

197 Publications

Trends in cardiovascular diseases burden and vascular risk factors in Italy: The Global Burden of Disease study 1990-2017.

Eur J Prev Cardiol 2021 May;28(4):385-396

School of Medicine and Surgery, Research Centre on Public Health (CESP), University of Milano-Bicocca, Italy.

Aims: An exhaustive and updated estimation of cardiovascular disease burden and vascular risk factors is still lacking in European countries. This study aims to fill this gap assessing the global Italian cardiovascular disease burden and its changes from 1990 to 2017 and comparing the Italian situation with European countries.

Methods: All accessible data sources from the 2017 Global Burden of Disease study were used to estimate the cardiovascular disease prevalence, mortality and disability-adjusted life years and cardiovascular disease attributable risk factors burden in Italy from 1990 to 2017. Furthermore, we compared the cardiovascular disease burden within the 28 European Union countries.

Results: Since 1990, we observed a significant decrease of cardiovascular disease burden, particularly in the age-standardised prevalence (-12.7%), mortality rate (-53.8%), and disability-adjusted life years rate (-55.5%). Similar improvements were observed in the majority of European countries. However, we found an increase in all-ages prevalence of cardiovascular diseases from 5.75 m to 7.49 m Italian residents. Cardiovascular diseases still remain the first cause of death (34.8% of total mortality). More than 80% of the cardiovascular disease burden could be attributed to known modifiable risk factors such as high systolic blood pressure, dietary risks, high low density lipoprotein cholesterol, and impaired kidney function.

Conclusions: Our study shows a decline in cardiovascular mortality and disability-adjusted life years, which reflects the success in reducing disability, premature death and early incidence of cardiovascular diseases. However, the burden of cardiovascular diseases is still high. An approach that includes the cooperation and coordination of all stakeholders of the Italian National Health System is required to further reduce this burden.
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http://dx.doi.org/10.1177/2047487320949414DOI Listing
May 2021

A nomogram to predict unfavourable outcome in patients receiving oral anticoagulants for atrial fibrillation after stroke.

Eur Stroke J 2020 Dec 26;5(4):384-393. Epub 2020 Nov 26.

Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.

Introduction: It is unknown whether the type of treatment (direct oral anticoagulant versus vitamin K antagonist) and the time of treatment introduction (early versus late) may affect the functional outcome in stroke patients with atrial fibrillation. We aimed to develop and validate a nomogram model including direct oral anticoagulant/vitamin K antagonist and early/late oral anticoagulant introduction for predicting the probability of unfavourable outcome after stroke in atrial fibrillation-patients.

Patients And Methods: We conducted an individual patient data analysis of four prospective studies. Unfavourable functional outcome was defined as three-month modified Rankin Scale score 3 -6. To generate the nomogram, five independent predictors including age (<65 years, reference; 65--79; or 80), National Institutes of Health Stroke Scale score (0--5 points, reference; 6--15; 16--25; or >25), acute revascularisation treatments (yes, reference, or no), direct oral anticoagulant (reference) or vitamin K antagonist, and early (7 days, reference) or late (8--30) anticoagulant introduction entered into a final logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve.

Results: A total of 2102 patients with complete data for generating the nomogram was randomly dichotomised into training ( = 1553) and test ( = 549) sets. The area under the receiver operating characteristic curve was 0.822 (95% confidence interval, CI: 0.800--0.844) in the training set and 0.803 (95% CI: 0.764--0.842) in the test set. The model was adequately calibrated (9.852;  = 0.276 for the Hosmer--Lemeshow test).

Discussion And Conclusion: Our nomogram is the first model including type of oral anticoagulant and time of treatment introduction to predict the probability of three-month unfavourable outcome in a large multicentre cohort of stroke patients with atrial fibrillation.
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http://dx.doi.org/10.1177/2396987320945840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856583PMC
December 2020

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes.

Eur Stroke J 2020 Dec 22;5(4):374-383. Epub 2020 Jul 22.

Internal Medicine, San Giuseppe Hospital, Empoli, Italy.

Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing.

Materials And Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke.

Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80).

Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events.

Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.
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http://dx.doi.org/10.1177/2396987320937116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856592PMC
December 2020

Editorial: Coronavirus disease 2019 and stroke: how to avoid a new lockdown for stroke patients.

Authors:
Valeria Caso

Curr Opin Neurol 2021 02;34(1):1-2

Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy.

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http://dx.doi.org/10.1097/WCO.0000000000000892DOI Listing
February 2021

PREvention of VENous Thromboembolism in Hemorrhagic Stroke Patients - PREVENTIHS Study: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis.

Eur Neurol 2020 13;83(6):566-575. Epub 2020 Nov 13.

Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.

Background: In this randomized trial, currently utilized standard treatments were compared with enoxaparin for the prevention of venous thromboembolism (VTE) in patients with intracerebral hemorrhage (ICH).

Methods: Enoxaparin (0.4 mg daily for 10 days) was started after 72 h from the onset of ICH. The primary outcome was symptomatic or asymptomatic deep venous thrombosis as assessed by ultrasound at the end of study treatment. The safety of enoxaparin was also assessed. We included the results of this study in a meta-analysis of all relevant studies comparing anticoagulants with standard treatments or placebo.

Results: PREVENTIHS was prematurely stopped after the randomization of 73 patients, due to the low recruitment rate. The prevalence of any VTE at 10 days was 15.8% in the enoxaparin group and 20.0% in the control group (RR 0.79 [95% CI 0.29-2.12]); 2.6% of enoxaparin and 8.6% of standard therapy patients had severe bleedings (RR 0.31 [95% CI 0.03-2.82]). When these results were meta-analyzed with the results of the selected studies (4,609 patients; 194 from randomized trials), anticoagulants were associated with a nonsignificant reduction in any VTE (OR 0.81; 95% CI 0.43-1.51), in pulmonary embolism (OR 0.53; 95% CI, 0.17-1.60), and in mortality (OR 0.85; 95% CI 0.64-1.12) without increase in hematoma enlargement (OR 0.97; 95% CI, 0.31-3.04).

Conclusions: In patients with acute ICH, the use of anticoagulants to prevent VTE was safe but the overall level of evidence was low due to the low number of patients included in randomized clinical trials.
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http://dx.doi.org/10.1159/000511574DOI Listing
May 2021

Non-vitamin K oral anticoagulants for secondary stroke prevention in patients with atrial fibrillation.

Eur Heart J Suppl 2020 Sep 15;22(Suppl I):I13-I21. Epub 2020 Sep 15.

Stroke Unit, University of Perugia, Santa Maria della Misericordia Hospital, Ospedale S. Maria della Misericordia S. Andrea delle Fratte, 06156 Perugia, Italy.

The aims of this article are to review the evidence regarding the use of non-vitamin K oral anticoagulants (NOACs) for secondary stroke prevention as compared to vitamin K antagonists in patients with atrial fibrillation (AF) and in patients with embolic strokes of uncertain source (ESUS), and when to initiate or resume anticoagulation after an ischaemic stroke or intracranial haemorrhage. Four large trials compared NOACs with warfarin in patients with AF. In our meta-analyses, the rate of all stroke or systemic embolism (SE) was 4.94% with NOACs vs. 5.73% with warfarin. Among the patients with AF and previous transient ischaemic attack or ischaemic stroke, the rate of haemorrhagic stroke was halved with a NOAC vs. warfarin, and the rate of major bleeding was 5.7% with a NOAC vs. 6.4% with warfarin. There was no significant difference in mortality. In a trial comparing apixaban with aspirin in patients with AF, the rate of stroke or SE was 2.4% at 1 year with apixaban vs. 9.2% at 1 year with aspirin and the rates of major bleeding were 4.1% with apixaban vs. 2.9% with aspirin. Data from registries confirmed the results from the randomized trials. Initiation or resumption of anticoagulation after ischaemic stroke or cerebral haemorrhage depends on the size and severity of stroke and the risk of recurrent bleeding. Two large trials tested the hypothesis that NOACs are more effective than 100 mg aspirin in patients with ESUS. Neither trial showed a significant benefit of the NOAC over aspirin. In the meta-analysis, the rate all stroke or SE was 4.94% with NOACs vs. 5.73% with warfarin and the rate of haemorrhagic stroke was halved with a NOAC. The four NOACs had broadly similar efficacy for the major outcomes in secondary stroke prevention.
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http://dx.doi.org/10.1093/eurheartj/suaa104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556747PMC
September 2020

Maintaining stroke care in Europe during the COVID-19 pandemic: Results from an international survey of stroke professionals and practice recommendations from the European Stroke Organisation.

Eur Stroke J 2020 Sep 10;5(3):230-236. Epub 2020 Jun 10.

Stroke Unit, Department of Neurology, Oslo University Hospital, Oslo, Norway.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has been placing an overwhelming burden on health systems, thus threatening their ability to operate effectively for acute conditions in which treatments are highly time sensitive, such as cerebrovascular disorders and myocardial infarction. As part of an effort to reduce the consequences of this outbreak on health service delivery to stroke patients, the European Stroke Organisation has undertaken a survey aimed at collecting information on the provision of stroke care during the pandemic.

Methods: Cross-sectional, web-based survey, conducted from 26 March through 1 April 2020 among stroke care providers, focused on reorganisation of health services, the delivery of acute and post-acute stroke care and the availability of personal protective equipment.

Results: A total of 426 stroke care providers from 55 countries completed the survey, most of whom worked in Europe (n = 375, 88%) and were stroke physicians/neurologists (n = 334, 78%). Among European respondents, 289 (77%) reported that not all stroke patients were receiving the usual care in their centres and 266 (71%) estimated that functional outcomes and recurrence rates of stroke patients would be negatively affected by the organisational changes caused by the pandemic. The areas considered as being most affected were acute care and rehabilitation. Most professionals had to adapt their activities and schedules and more than half reported shortage of protective equipment.

Discussion: Strategies to maintain availability of stroke care during the COVID-19 outbreak are crucial to prevent indirect mortality and disability due to suboptimal care.

Conclusion: European Stroke Organisation proposes a set of targeted actions for decision makers facing this exceptional situation.
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http://dx.doi.org/10.1177/2396987320933746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538757PMC
September 2020

Stroke care in Italy: An overview of strategies to manage acute stroke in COVID-19 time.

Eur Stroke J 2020 Sep 26;5(3):222-229. Epub 2020 Jul 26.

Stroke Unit and Division of Internal and Cardiovascular Medicine, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy.

Purpose: To analyse structural and non-structural modifications of acute stroke care pathways undertaken at healthcare institutions across the regions of Italy due to the coronavirus disease 2019 (COVID-19) pandemic.

Methods: Research on National decrees specific for the pandemic was carried out. The stroke pathways of four Italian regions from North to South, such as Lombardy, Veneto, Lazio and Campania, were analysed before and after the pandemic outbreak.

Findings: On 29 February 2020, the Italian Minister of Health issued national guidelines on how to address the COVID-19 emergency. Stroke management was affected and required changes, basically resulting in the need to prioritise the ongoing COVID-19 emergency. In the most affected regions, the closure of departments and hospitals led to a complete reorganisation of previously functioning stroke networks. With the closure of several Stroke Units and Stroke Centres, the transportation time to hospital lengthened significantly, especially for the outlying populations.

Discussion: The COVID-19 pandemic outbreak has been spreading rapidly in Italy and placing an overwhelming burden on healthcare systems. In response to this, political and healthcare decision-makers worked together to develop and implement efforts to sustain the national healthcare system while fighting the pandemic. Stroke care pathways changed during the pandemic and different organisational models were applied in the most affected regions.

Conclusions: Stroke treatment pathways will need to be redesigned so to guarantee that severe and acute disease patients do not lose their rights to the access and delivery of care during the COVID-19 pandemics.
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http://dx.doi.org/10.1177/2396987320942622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538763PMC
September 2020

Reperfusion strategies in stroke due to isolated cervical internal carotid artery occlusion: systematic review and treatment comparison.

Neurol Sci 2021 Jun 10;42(6):2301-2308. Epub 2020 Oct 10.

Stroke Unit and Division of Cardiovascular Medicine, University of Perugia-S. Maria della Misericordia Hospital, Perugia, Italy.

Introduction: Despite intravenous thrombolysis (IVT) and endovascular treatment (EVT) have been demonstrated effective in acute ischemic stroke (AIS) due to large vessel occlusions, there are still no conclusive data to guide treatment in stroke due to cervical internal carotid artery (ICA) occlusion. We systematically reviewed available literature to compare IVT, EVT, and bridging (IVT + EVT) and define optimal treatment.

Methods: Systematic review followed predefined protocol (Open-Science-Framework osf.io/bfykj ). MEDLINE, EMBASE, and Cochrane CENTRAL were searched. Results were restricted to studies in English, with sample size ≥ 10 and follow-up ≥30 days. Primary outcomes were favorable outcome (mRS ≤ 2), mortality, and symptomatic intracerebral hemorrhage(sICH), defined according to study original report. Newcastle-Ottawa scale was used for bias assessment.

Results: Seven records of 930 screened were included in meta-analysis. Quality of studies was low-to-fair in 5, good in 2. IVT (n = 450) did not differ for favorable outcome and mortality compared to EVT (n = 150), though having lower rate of sICH (OR = 0.4, 95% CI 0.2-0.8). Compared to IVT, bridging (IVT + EVT) was associated with higher rate of favorable outcome (OR = 2.2, 95% CI 1.3-3.7). Compared to EVT, bridging (IVT + EVT) provided higher rate of favorable outcome (OR = 1.9, 95% CI 1.1-3.4), with a marginally increased risk of sICH (OR = 2.1, 95% CI 1-4.4) but similar mortality rates.

Conclusions: Our systematic review highlights that, in acute ischemic stroke associated with isolated cervical ICA occlusion, bridging (IVT + EVT) might lead to higher rate of functional independence at follow-up, without increasing mortality. The low quality of available studies prevents from drawing firm conclusions, and randomized-controlled clinical trials are critically needed to define optimal treatment in this AIS subgroup.
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http://dx.doi.org/10.1007/s10072-020-04735-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159826PMC
June 2021

How to Be Savvy About Gender Disparities in Academic Stroke Medicine: Five Practical Strategies.

Stroke 2020 Sep 19;51(9):e261-e265. Epub 2020 Aug 19.

Department of Physical Medicine & Rehabilitation, Harvard Medical School (J.K.S.).

In the past decade, stroke medicine has evolved from discovery of innovative diagnostic tools to implementation of new treatments. These advances are projected to increase the demand for stroke neurologists in academic and clinical practices, but hopefully with equitable opportunities for everyone across the gender spectrum. Academic medicine provides opportunities to participate in clinical care, teaching, research, and administration. The early career stage is short-focused on finding an academic niche and developing new skills that will help you navigate the academic environment. A recent InterSECT article emphasized the critical role of women's leadership in stroke medicine. In this article, we reflect on workforce gender disparities and provide 5 practical strategies that may help women overcome barriers and advance their work mission.
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http://dx.doi.org/10.1161/STROKEAHA.120.029546DOI Listing
September 2020

Safety of Anticoagulation in Patients Treated With Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation.

Stroke 2020 08 10;51(8):2347-2354. Epub 2020 Jul 10.

Internal Medicine, Santa Maria Nuova Hospital, Firenze, Italy (V. Vannucchi, L.M.).

Background And Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention.

Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features.

Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]).

Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant.
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http://dx.doi.org/10.1161/STROKEAHA.120.030143DOI Listing
August 2020

Enhancing and accelerating stroke treatment in Eastern European region: Methods and achievement of the ESO EAST program.

Eur Stroke J 2020 Jun 20;5(2):204-212. Epub 2020 Jan 20.

Department of Neurology, Med Campus III, Kepler University Hospital, Linz, Austria.

Introduction: Despite the availability of prevention and therapies of stroke, their implementation in clinical practice, even of low-cost ones, remains poor. In 2015, the European Stroke Organisation (ESO) initiated the ESO Enhancing and Accelerating Stroke Treatment (EAST) program, which aims to improve stroke care quality, primarily in Eastern Europe. Here, we describe its methods and milestones.

Patients And Methods: The ESO EAST program is using an implementation strategy based on a 'detecting-understanding-reducing disparities' conceptual framework: stroke care quality is first measured (after developing a platform for data collection), gaps are identified in the current service delivery, and ultimately feedback is provided to participating hospitals, followed by the application of interventions to reduce disparities. The ESO EAST program is carried out by establishing a stroke quality registry, stroke management infrastructure, and creating education and training opportunities for healthcare professionals.

Results: Program management and leadership infrastructure has been established in 19 countries (Country Representatives in 22 countries, National Steering Committee in 19 countries). A software platform for data collection and analysis: gistry of troke Care uality was developed, and launched in 2016, and has been used to collect data from over 90,000 patients from >750 hospitals and 56 countries between September 2016 and May 2019. Training in thrombolysis, nursing and research skills has been initiated.

Discussion: ESO EAST is the first pan-Eastern European (and beyond) multifaceted quality improvement intervention putting evidence-informed policies into practice. Continuous monitoring of stroke care quality allows hospital-to-hospital and country-to-country benchmarking and identification of the gaps and needs in health care.
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http://dx.doi.org/10.1177/2396987319897156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313365PMC
June 2020

SiPP (Stroke in Pregnancy and Postpartum): A prospective, observational, international, multicentre study on pathophysiological mechanisms, clinical profile, management and outcome of cerebrovascular diseases in pregnant and postpartum women.

Eur Stroke J 2020 Jun 6;5(2):193-203. Epub 2019 Dec 6.

Department of Neurosciences (Neurology), Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal.

Rationale: Cerebrovascular diseases associated with pregnancy and postpartum period are uncommon; however, they can have an important impact on health of both women and foetus or newborn.

Aims: To evaluate the frequency, characteristics and management of cerebrovascular events in pregnant/postpartum women, to clarify pathophysiological mechanisms underlying the occurrence of these events including biomolecular aspects, and to assess the short- and long-term cerebrovascular and global cardiovascular outcome of these patients, their predictors and infant outcome.

Methods And Design: This is an observational, prospective, multicentre, international case-control study. The study will include patients with cerebrovascular events during pregnancy and/or within six months after delivery. For each included case, two controls will be prospectively recruited: one pregnant or puerperal subject without any history of cerebrovascular event and one non-pregnant or non-puerperal subject with a recent cerebrovascular event. All controls will be matched by age, ethnicity and type of cerebrovascular event with their assigned cases. The pregnant controls will be matched also by pregnancy weeks/trimester. Follow-up will last 24 months for the mother and 12 months for the infant.

Summary: To better understand causes and outcomes of uncommon conditions like pregnancy/postpartum-related cerebrovascular events, the development of multisite, multidisciplinary registry-based studies, such as the Stroke in Pregnancy and Postpartum study, is needed in order to collect an adequate number of patients, draw reliable conclusions and give definite recommendations on their management.
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http://dx.doi.org/10.1177/2396987319893512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313370PMC
June 2020

COVID-19 Infection and Neurological Complications: Present Findings and Future Predictions.

Neuroepidemiology 2020 1;54(5):364-369. Epub 2020 Jul 1.

Center for Neurodegenerative Diseases and the Aging Brain, Department of Clinical Research in Neurology, University of Bari "Aldo Moro"Bari, "Pia Fondazione Cardinale G. Panico", Tricase, Italy.

The present outbreak caused by SARS-CoV-2, an influenza virus with neurotropic potential, presents with neurological manifestations in a large proportion of the affected individuals. Disorders of the central and peripheral nervous system are all present, while stroke, ataxia, seizures, and depressed level of consciousness are more common in severely affected patients. People with these severe complications are most likely elderly with medical comorbidities, especially hypertension and other vascular risk factors. However, postinfectious complications are also expected. Neurological disorders as sequelae of influenza viruses have been repeatedly documented in the past and include symptoms, signs, and diseases occurring during the acute phase and, not rarely, during follow-up. Postinfectious neurological complications are the result of the activation of immune mechanisms and can explain the insurgence of immune-mediated diseases, including the Guillain-Barré syndrome and other diseases of the central and peripheral nervous system that in the past occurred as complications of viral infections and occasionally with vaccines. For these reasons, the present outbreak calls for the introduction of surveillance systems to monitor changes in the frequency of several immune-mediated neurological diseases. These changes will determine a reorganization of the measures apt to describe the interaction between the virus, the environment, and the host in areas of different dimensions, from local communities to regions with several millions of inhabitants. The public health system, mainly primary care, needs to be strengthened to ensure that research and development efforts are directed toward right needs and directions. To cope with the present pandemic, better collaboration is required between international organizations along with more research funding, and tools in order to detect, treat, and prevent future epidemics.
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http://dx.doi.org/10.1159/000508991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445369PMC
October 2020

Neurological manifestations and implications of COVID-19 pandemic.

Ther Adv Neurol Disord 2020 9;13:1756286420932036. Epub 2020 Jun 9.

4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide, with a vast majority of confirmed cases presenting with respiratory symptoms. Potential neurological manifestations and their pathophysiological mechanisms have not been thoroughly established. In this narrative review, we sought to present the neurological manifestations associated with coronavirus disease 2019 (COVID-19). Case reports, case series, editorials, reviews, case-control and cohort studies were evaluated, and relevant information was abstracted. Various reports of neurological manifestations of previous coronavirus epidemics provide a roadmap regarding potential neurological complications of COVID-19, due to many shared characteristics between these viruses and SARS-CoV-2. Studies from the current pandemic are accumulating and report COVID-19 patients presenting with dizziness, headache, myalgias, hypogeusia and hyposmia, but also with more serious manifestations including polyneuropathy, myositis, cerebrovascular diseases, encephalitis and encephalopathy. However, discrimination between causal relationship and incidental comorbidity is often difficult. Severe COVID-19 shares common risk factors with cerebrovascular diseases, and it is currently unclear whether the infection represents an independent stroke risk factor. Regardless of any direct or indirect neurological manifestations, the COVID-19 pandemic has a huge impact on the management of neurological patients, whether infected or not. In particular, the majority of stroke services worldwide have been negatively influenced in terms of care delivery and fear to access healthcare services. The effect on healthcare quality in the field of other neurological diseases is additionally evaluated.
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http://dx.doi.org/10.1177/1756286420932036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284455PMC
June 2020

Preserving stroke care during the COVID-19 pandemic: Potential issues and solutions.

Neurology 2020 07 8;95(3):124-133. Epub 2020 May 8.

From the Departments of Neurology, Neurosurgery & Epidemiology (E.C.L.), University of Iowa, Iowa City, IA; Cerebrovascular Center (A.N.R.), Cleveland Clinic, OH; Department of Neurology (J.B.), Loyola University Chicago, Maywood, IL; Department of Neurology (D.L.B.), University of Michigan, Ann Arbor, MI; Department of Neurology (C.D.B.), Wake Forest School of Medicine, Winston-Salem, NC; Stroke Unit (V.C.), University of Perugia, Italy; Department of Neurology (A.C.), Hospital Clinic, Barcelona, Spain; Department of Neurology (C.J.C., D.L.T.), University of Washington, Seattle, WA; Department of Neurology (S.C.-F.), Texas Tech University, El Paso, TX; Departments of Neurology & Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Neurological Sciences (P.F.), University of Nebraska, Omaha, NE; Department of Neurology & Neurosurgery (M.T.F.), Vanderbilt University, Nashville, TN; Department of Neurology (L.B.G.), University of Kentucky, Lexington, KY; Department of Neurology (N.R.G.), McGovern Medical School at UTHealth, Houston, TX; Department of Health Management and Policy (B.K.), University of Iowa, Iowa City, IA; Department of Neurology (P.K.), University of Cincinnati, OH; Department of Adult Health & Gerontology Nursing (S.L.), Rush University, Chicago, IL; Department of Neurology (D.S.L.), UCLA; Department of Neurology (J.J.M.), University of Utah, Salt Lake City, UT; Neurocritical Care, OhioHealth Riverside Methodist Hospital (A.M.M.), Columbus, OH; Department of Neurology (J.G.R.), University of Miami, FL; Department of Neurology (N.S.), University Southern California, Los Angeles, CA; Department of Neurology (L.H.S.), Yale School of Medicine, New Haven, CT; Department of Neurology (B.S.), University of Massachusetts, Worcester, MA; Department of Neurology (A.N.S.), University of Florida, Gainesville, FL; Department of Neurology (W.S.), UCSF; Department of Neurology (D.Z.W.), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology & Neurosurgery (D.R.Y.), University of Miami, FL; and Department of Neurology (B.B.W.), University of Virginia, Charlottesville, VA.

The coronavirus 2019 (COVID-19) pandemic requires drastic changes in allocation of resources, which can affect the delivery of stroke care, and many providers are seeking guidance. As caregivers, we are guided by 3 distinct principles that will occasionally conflict during the pandemic: (1) we must ensure the best care for those stricken with COVID-19, (2) we must provide excellent care and advocacy for patients with cerebrovascular disease and their families, and (3) we must advocate for the safety of health care personnel managing patients with stroke, with particular attention to those most vulnerable, including trainees. This descriptive review by a diverse group of experts in stroke care aims to provide advice by specifically addressing the potential impact of this pandemic on (1) the quality of the stroke care delivered, (2) ethical considerations in stroke care, (3) safety and logistic issues for providers of patients with stroke, and (4) stroke research. Our recommendations on these issues represent our best opinions given the available information, but are subject to revision as the situation related to the COVID-19 pandemic continues to evolve. We expect that ongoing emergent research will offer additional insights that will provide evidence that could prompt the modification or removal of some of these recommendations.
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http://dx.doi.org/10.1212/WNL.0000000000009713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455350PMC
July 2020

Rates and Determinants for the Use of Anticoagulation Treatment before Stroke in Patients with Known Atrial Fibrillation.

Cerebrovasc Dis Extra 2020 6;10(2):44-49. Epub 2020 May 6.

Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Santa Maria della Misericordia Hospital, Perugia, Italy.

Introduction And Objective: Even though the introduction of less cumbersome anticoagulant agents has improved, the rates ofoverall anticoagulant treatment in eligible patients with atrial fibrillation (AF) remain to be defined. We aimed to assess the rates of and determinants for the use of anticoagulation treatment before stroke in patients with known AF since the introduction of direct oral anticoagulants (DOAC) in clinical practice.

Methods: Consecutive patients admitted to an individual stroke unit, from September 2013 through July 2019, for acute ischemic stroke or transient ischemic attack (TIA) with known AF before the event were included in the study. Logistic regression analysis was used to identify independent predictors of the use of anticoagulant treatment.

Results: Overall, 155 patients with ischemic stroke/TIA and known AF were included in this study. Among 152 patients with a CHA2DS2-VASc score >1, 43 patients were not receiving any treatment, 47 patients were receiving antiplatelet agents, and the remaining 62 patients were on oral anticoagulants. Among 34 patients on DOAC, 13 were receiving a nonlabeled reduced dose and 18 out of 34 patients on vitamin K antagonists had an INR value <2 at the time of admission. Before stroke, only 34 out of 155 patients (21.9%) were adequately treated according to current guidelines. Previous stroke/TIA was the only independent predictor of the use of anticoagulant therapy.

Conclusions: Only 21.9% of the patients hospitalized for a stroke or TIA with known AF before the event were adequately treated according to recent treatment guidelines. It is important to improve medical information about the risk of AF and the efficacy of anticoagulants in stroke prevention.
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http://dx.doi.org/10.1159/000506923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250375PMC
September 2020

No lockdown for neurological diseases during COVID19 pandemic infection.

Neurol Sci 2020 May;41(5):999-1001

Neurological Sciences, Department, Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.

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http://dx.doi.org/10.1007/s10072-020-04389-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138901PMC
May 2020

SMASH-U classification: a tool for aetiology-oriented management of patients with acute haemorrhagic stroke.

Intern Emerg Med 2021 Jan 8;16(1):109-114. Epub 2020 Apr 8.

Stroke Unit and Division of Internal and Cardiovascular Medicine, Santa Maria della Misericordia Hospital, University of Perugia, Piazzale Menghini 1, 06129, Perugia, Italy.

Intracerebral haemorrhage (ICH) is responsible for disproportionately high morbidity and mortality rates. The most used ICH classification system is based on the anatomical site. We used SMASH-U, an aetiological based classification system for ICH by predefined criteria: structural vascular lesions (S), medication (M), amyloid angiopathy (A), systemic disease (S), hypertension (H), or undetermined (U). We aimed to correlate SMASH-U classification of our patients to the intra-hospital mortality rates. We performed a single centre retrospective study at the Santa Maria Della Misericordia Hospital, Perugia (Italy) including consecutive patients between January 2009 and July 2017 assigned with 431 ICD-9 (International Classification of Diseases-9). We classified the included patients using SMASH-U criteria, and we analysed the association between SMASH-U aetiology and ICH risk factors to the outcome defined as intra-hospital mortality, using multivariable logistic regression analysis. The higher intra-hospital mortality rate was detected in the systemic disease (36.1%), medication (31.5%), and undetermined (29.4%) groups. At multivariable analysis, medication and systemic disease groups resulted associated with the outcome (odds ratio 3.47; 95% CI 1.15-10.46; P = 0.02 and 3.64; 95% CI 1.47-9.01; P = 0.005, respectively). Furthermore, age and high NIHSS at admission resulted significantly associated with intra-hospital mortality (odds ratio 1.01; 95% CI 1-1.03; P = 0.04 and 1.12; 95% CI 1.03-1.22; P = 0.008, respectively). In our retrospective study, the aetiology-oriented classification system SMASH-U showed to be potentially predictive of intra-hospital mortality of acute haemorrhagic stroke patients and it may support clinicians in the acute ICH management.
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http://dx.doi.org/10.1007/s11739-020-02330-2DOI Listing
January 2021

Acute hematoma expansion after spontaneous intracerebral hemorrhage: risk factors and impact on long-term prognosis.

Neurol Sci 2020 Sep 25;41(9):2503-2509. Epub 2020 Mar 25.

Stroke Unit, University of Perugia - Santa Maria della Misericordia Hospital, Perugia, Italy.

Introduction: Hematoma expansion (HE) after intracerebral hemorrhage (ICH) is associated with short-term mortality, but its impact on long-term prognosis is still unclear. The aim of this study was to evaluate the impact of HE on long-term survival and functional status after spontaneous ICH.

Methods: Consecutive patients admitted with spontaneous ICH were prospectively enrolled and followed up for a minimum of 2 years. We compared short-term (< 30 days) and long-term survival and functional status between ICH patients with HE (HE+) and those without (HE-). Main outcomes were mortality and poor outcome, defined as modified Rankin Scale ≥ 3. Secondary outcomes included recurrent ICH, admission to institutionalized care, and ischemic events (stroke, myocardial infarction, and systemic embolism).

Results: Overall, 140 patients were included (mean age 74.9 years, male 59.3%) and followed up for a mean of 2.25 years. HE+ patients (25.7%) had larger hematoma volume at admission (23.8 ml vs 15.3 ml, p < 0.05), higher NIHSS score (14.6 vs 10.5, p < 0.05) and higher cumulative mortality (59.3% vs 39.2%, p < 0.05) compared to HE- patients. Survival analysis showed that HE+ confers higher mortality and worse functional status at all time points. HE did not associate with secondary outcomes.

Discussion: HE translates into higher mortality and functional dependence over long-term follow-up. Strategies limiting HE might benefit long-term functional status.
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http://dx.doi.org/10.1007/s10072-020-04356-yDOI Listing
September 2020

Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation.

Ann Neurol 2020 Feb 12. Epub 2020 Feb 12.

Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.

Objective: It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.

Methods: We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OAC ) with those without prior oral anticoagulation (OAC ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OAC ) with those who continued the same anticoagulation as secondary prevention (OAC ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA DS -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OAC (n = 1,195) and OAC (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OAC was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OAC (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OAC (n = 585).

Interpretation: Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA DS -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. ANN NEUROL 2020.
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http://dx.doi.org/10.1002/ana.25700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383617PMC
February 2020

Women in the European Stroke Organisation: One, two, many… - A and approach.

Eur Stroke J 2019 Sep 9;4(3):247-253. Epub 2019 Apr 9.

Stroke Unit, Santa Maria della Misericordia, University of Perugia, Perugia, Italy.

Background: An increasing proportion of physicians are women, yet they still face challenges with career advancement. In 2014, the European Stroke Organisation established the goal of increasing the number and participation of women within the society using a and approach. The 'Women's Initiative for Stroke in Europe' was created the same year by a group of women active within the organisation. We aimed to assess the current status of women in European Stroke Organisation, and to explore the change in sex differences after the introduction of focused approaches to address disparities in 2014.

Methods: Using organisational records, we collected data on sex differences in core activities from 2008 up to 2017 including membership, participation in conferences, courses and in the official journal of the society, and positions of seniority and leadership. We estimated sex distribution differences in each of the activities from 2014 to date.

Results: In 2017, the proportion of female members was 40%, while 24% of fellows, 22% of the executive board and 19% of the editorial board in the official journal of the society were women. From 2014 to 2017, there was a significant increase in the proportion of female members (p = 0.0002) and in women participating in the annual conference as faculty (p = 0.001). There was no significant change in the sex distribution among the faculty members in junior educational activities (≤27%) or fellows.

Interpretation: In 2017, the proportion of women holding positions of seniority and leadership is still significantly lower to the proportion of women attending educational activities. Transparent data on sex distribution will assist implementing tailored programmes to achieve progress against sex-based barriers.
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http://dx.doi.org/10.1177/2396987319841979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960690PMC
September 2019

Planning of stroke care and urgent prehospital care across Europe: Results of the ESO/ESMINT/EAN/SAFE Survey.

Eur Stroke J 2019 Dec 19;4(4):329-336. Epub 2019 Mar 19.

Department of Neurology, University Hospital Bern and University of Bern, Inselspital, Bern, Switzerland.

Introduction: Adequate planning and implementation of stroke systems of care is key to guarantee a rapid healthcare response and delivery of specific reperfusion therapies among candidates. We assessed the availability of stroke care plans in Europe, and evaluated their impact on rates of reperfusion therapies for stroke.

Patients: Based on the European Stroke Organisation (ESO), the European Society of Minimally Invasive Neurological Therapy (ESMINT), the European Academy of Neurology (EAN), and the Stroke Alliance for Europe (SAFE) survey, we analysed specific prespecified items in the questionnaire regarding availability and adequacy of stroke care plans, organised prehospital care and their potential impact on rates of delivery of reperfusion therapies for stroke at the country level.

Results: Of 44 participating European countries, 37 have stroke care plans that operate at national and/or regional levels. Most stroke care plans take responsibility for the organisation/implementation of stroke systems of care (86%), quality of care assessment (77%), and act as a liaison between emergency medical systems and stroke physicians (79%). As for stroke systems of care, the focus is mainly on prehospital and in-hospital acute stroke care (Code Stroke systems available in 37/44 countries). Preferred urgent transport is via non-medicalised ambulances (70%). Presence of stroke care plans, stroke registry data, transport of urgent stroke patients via non-medicalised ambulances, and drip-and-ship routing of acute patients showed higher reperfusion treatment rates.

Discussion: Availability of stroke care plans, still absent in some European countries, as well as some features of the stroke systems of care are associated with higher reperfusion treatment rates.

Conclusion: Stroke is not yet a priority everywhere in Europe, which is a barrier to the spread of reperfusion therapies for stroke.
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http://dx.doi.org/10.1177/2396987319837106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921941PMC
December 2019

Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window.

Neurology 2020 03 31;94(12):e1241-e1248. Epub 2019 Dec 31.

From the Second Department of Neurology (G.T., A.H.K.), "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Department of Neurology (G.T., A.V.A.), University of Tennessee Health Science Center, Memphis; Department of Neurology (A.H.K., C.K.), St. Josef Hospital, Ruhr University Bochum, Germany; Department of Neurology (K.M.), Allegheny Health Network, Pittsburgh, Pennsylvania; Department of Neurology (A.S., A.D.B.), University of Texas Health Science Center, Houston; Department of Neurology (M.K.), Universitaetsklinikum Essen, Germany; Department of Neurology (N.A.), Karolinska University Hospital; Department of Clinical Neuroscience (N.A.), Karolinska Institute, Stockholm, Sweden; Stroke Unit and Division of Cardiovascular Medicine (V.C.), University of Perugia, Italy; and Departments of Neurology and Neurogeriatry (P.D.S.), Johannes Wesling Medical Center, Ruhr University Bochum, Minden, Germany.

Objective: To assess the utility of IV thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS) with unclear symptom onset time or outside the 4.5-hour time window selected by advanced neuroimaging.

Methods: We performed random-effects meta-analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes: 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores 0-1), 3-month functional independence (FI; mRS scores 0-2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS scores), symptomatic intracranial hemorrhage (sICH), and complete recanalization (CR).

Results: We identified 4 eligible randomized clinical trials (859 total patients). In unadjusted analyses, IVT was associated with a higher likelihood of 3-month FFO (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.12-1.96), FI (OR 1.42, 95% CI 1.07-1.90), sICH (OR 5.28, 95% CI 1.35-20.68), and CR (OR 3.29, 95% CI 1.90-5.69), with no significant difference in the odds of all-cause mortality risk at 3 months (OR 1.75, 95% CI 0.93-3.29). In the adjusted analyses, IVT was also associated with higher odds of 3-month FFO (adjusted OR [OR] 1.62, 95% CI 1.20-2.20), functional improvement (OR 1.42, 95% CI 1.11-1.81), and sICH (OR 6.22, 95% CI 1.37-28.26). There was no association between IVT and FI (OR 1.61, 95% CI 0.94-2.75) or all-cause mortality (OR 1.75, 95% CI 0.93-3.29) at 3 months. No evidence of heterogeneity was evident in any of the analyses ( = 0).

Conclusion: IVT in patients with AIS with unknown symptom onset time or elapsed time from symptom onset >4.5 hours selected with advanced neuroimaging results in a higher likelihood of CR and functional improvement at 3 months despite the increased risk of sICH.
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http://dx.doi.org/10.1212/WNL.0000000000008904DOI Listing
March 2020

Imaging markers of small vessel disease and brain frailty, and outcomes in acute stroke.

Neurology 2020 02 27;94(5):e439-e452. Epub 2019 Dec 27.

From the Stroke Trials Unit (J.P.A., L.J.W., N.S., P.M.B.) and Radiological Sciences Research Group (R.A.D.), Division of Clinical Neurosciences, University of Nottingham; Stroke (J.P.A., N.S., P.M.B.), Nottingham University Hospitals NHS Trust, UK; Stroke Center (A.A.), IRCSS Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy; Department of Medical Imaging (J.L.B.), College of Medicine, University of Arizona, Tucson; Department of Internal Medicine and Cardiology (E.B.), Oslo University Hospital, Norway; School of Medicine (L.A.C.), University of Western Australia, Crawley; Department of Neuroradiology (A.M.C.), Division of Clinical Neurosciences, Western General Hospital, Edinburgh, UK; Stroke Unit (V.C.), Santa Maria della Misericordia Hospital, University of Perugia, Italy; Neurology (H.K.C.), Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Department of Medicine (J.G.), Hawke's Bay District Health Board, Hastings, New Zealand; Department of Neuroradiology (P.K.), Nottingham University Hospitals, Queen's Medical Centre, UK; Department of Neurology (S.S.), Clinical County Emergency Hospital, Targu Mures, Romania; and Division of Neuroimaging Sciences (J.M.W.), Centre for Clinical Brain Sciences, Dementia Research Institute, University of Edinburgh, UK.

Objective: To assess the association of baseline imaging markers of cerebral small vessel disease (SVD) and brain frailty with clinical outcome after acute stroke in the Efficacy of Nitric Oxide in Stroke (ENOS) trial.

Methods: ENOS randomized 4,011 patients with acute stroke (<48 hours of onset) to transdermal glyceryl trinitrate (GTN) or no GTN for 7 days. The primary outcome was functional outcome (modified Rankin Scale [mRS] score) at day 90. Cognition was assessed via telephone at day 90. Stroke syndrome was classified with the Oxfordshire Community Stroke Project classification. Brain imaging was adjudicated masked to clinical information and treatment and assessed SVD (leukoaraiosis, old lacunar infarcts/lacunes, atrophy) and brain frailty (leukoaraiosis, atrophy, old vascular lesions/infarcts). Analyses used ordinal logistic regression adjusted for prognostic variables.

Results: In all participants and those with lacunar syndrome (LACS; 1,397, 34.8%), baseline CT imaging features of SVD and brain frailty were common and independently associated with unfavorable shifts in mRS score at day 90 (all participants: SVD score odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07-1.24; brain frailty score OR 1.25, 95% CI 1.17-1.34; those with LACS: SVD score OR 1.30, 95% CI 1.15-1.47, brain frailty score OR 1.28, 95% CI 1.14-1.44). Brain frailty was associated with worse cognitive scores at 90 days in all participants and in those with LACS.

Conclusions: Baseline imaging features of SVD and brain frailty were common in lacunar stroke and all stroke, predicted worse prognosis after all acute stroke with a stronger effect in lacunar stroke, and may aid future clinical decision-making.

Identifier: ISRCTN99414122.
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http://dx.doi.org/10.1212/WNL.0000000000008881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080284PMC
February 2020

Artery occlusion independently predicts unfavorable outcome in cervical artery dissection.

Neurology 2020 01 22;94(2):e170-e180. Epub 2019 Nov 22.

From the Department of Neurology and Stroke Center (C.T., G.M.D.M., A. Polymeris, H.G., L.H.B., S.T.E., P.L.), University Hospital Basel and University of Basel; Neurorehabilitation Unit (C.T., H.G., S.T.E.), University of Basel and University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, Basel, Switzerland; Departments of Neurology (C.G.-G., M.K.) and Vascular and Endovascular Surgery (C.G.-G.), Heidelberg University Hospital, Germany; Department of Neurology (B.G.S., U.F., H.S., M.A.), University Hospital Bern; Ospedale San Giovanni (B.G.S.), Bellinzona, Switzerland; Department of Neurology (T.M.M., T.T.), Helsinki University Central Hospital, Finland; Department of Neurology (S.D.), Bordeaux University Hospital; Inserm U1219 (S.D.), Bordeaux; University of Bordeaux (S.D.), France; Department of Neurology (S.D.), Boston University School of Medicine, MA; Department of Clinical and Experimental Sciences (A.Pezzini.), Neurology Clinic, University of Brescia, Italy; Department of Neurology (J.J.M.), University of Utah, Salt Lake City; Departments of Neurology and Public Health Sciences (A.M.S., B.B.W.), University of Virginia Health System, Charlottesville; Univ-Lille (D.L.), Inserm U1171, CHU Lille, France; Neuro Center (R.B.), Clinic Hirslanden, Zurich, Switzerland; Stroke Unit and Division of Internal and Cardiovascular Medicine (V.C.), University of Perugia, Italy; Centre Hospitalier Universitaire Dijon Bourgogne (Y.B.), EA7460, Pathophysiology and Epidemiology of Cardio-Cerebro-Vascular Diseases, University of Burgundy, Dijon, France; Department of Neurology (H.S.), University Hospital of Zurich, Switzerland; Stroke Theme (V.T.), Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg; Department of Neurology (V.T.), Austin Health, Heidelberg, Victoria, Australia; Cerebrovascular Unit Fondazione IRCCS Istituto Neurologico Carlo Besta (A.B.), Milan, Italy; Swiss National Accident Insurance Institution (T.B.), Lucerne, Switzerland; Normandie Université (E.T.), Université Caen Normandie, Inserm U1037, Department of Neurology, CHU Caen Normandie; Department of Neurology (E.T.), CH Sainte-Anne, University Paris Descartes, France; Department of Neurology (J.J.M.), Sanatorio Allende, Cordoba, Argentina; Department of Neurology (H.C.), Lariboisière Hospital, Paris, France; Department of Neurology (T.T.), Sahlgrenska University Hospital; and Department of Clinical Neuroscience Institute for Neuroscience and Physiology (T.T.), Sahlgrenska Academy at University of Gothenburg, Sweden.

Objective: To assess the impact of dissected artery occlusion (DAO) on functional outcome and complications in patients with cervical artery dissection (CeAD).

Methods: We analyzed combined individual patient data from 3 multicenter cohorts of consecutive patients with CeAD (the Cervical Artery Dissection and Ischemic Stroke Patients [CADISP]-Plus consortium dataset). Patients with data on DAO and functional outcome were included. We compared patients with DAO to those without DAO. Primary outcome was favorable functional outcome (i.e., modified Rankin Scale [mRS] score 0-1) measured 3-6 months from baseline. Secondary outcomes included delayed cerebral ischemia, major hemorrhage, recurrent CeAD, and death. We performed univariate and multivariable binary logistic regression analyses and calculated odds ratios (OR) with 95% confidence intervals (CI), with adjustment for potential confounders.

Results: Of 2,148 patients (median age 45 years [interquartile range (IQR) 38-52], 43.6% women), 728 (33.9%) had DAO. Patients with DAO more frequently presented with cerebral ischemia (84.6% vs 58.5%, < 0.001). Patients with DAO were less likely to have favorable outcome when compared to patients without DAO (mRS 0-1: 59.6% vs 80.1%, < 0.001). After adjustment for age, sex, and initial stroke severity, DAO was independently associated with less favorable outcome (mRS 0-1: OR 0.65, CI 0.50-0.84, = 0.001). Delayed cerebral ischemia occurred more frequently in patients with DAO than in patients without DAO (4.5% vs 2.9%, = 0.059).

Conclusion: DAO independently predicts less favorable functional outcome in patients with CeAD. Further research on vessel patency, collateral status and effects of revascularization therapies particularly in patients with DAO is warranted.
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http://dx.doi.org/10.1212/WNL.0000000000008654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988986PMC
January 2020

A tool to identify patients with embolic stroke of undetermined source at high recurrence risk.

Neurology 2019 12 29;93(23):e2094-e2104. Epub 2019 Oct 29.

From the Department of Internal Medicine (G.N., K.P., E. Karagkiozi, V.P., K.M.), Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; Department of Clinical Therapeutics (G.G., A.V., E. Koroboki, E.M., K.V.), Medical School of Athens, Alexandra Hospital, Greece; Stroke Center and Neurology Service (G.S., D.S., A.E., S.N., P.M.), Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland; Department of Neurology (E.K.), National and Kapodistrian University of Athens, Greece; Division of Brain Sciences (E.K.), Department of Stroke Medicine, Imperial College, London, UK; Stroke Unit (A.R.-C., E.C.-G., J.R.), Department of Neurology, Hospital del Mar, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autònoma de Barcelona, Spain; Stroke Unit (V.A., V.C., M.P.), University of Perugia, Italy; Department of Neurology and Stroke Center (E.D.-T., B.F., J.R.P., S.S.-V.), La Paz University Hospital-Autónoma University of Madrid, IdiPAZ Health Research Institute, Spain; Stroke Clinic (A.A.), Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico; Department of Neurology (S.F.A., L.P., M.G.-S., M.A.H.), Institute for Neurological Research, FLENI, Buenos Aires, Argentina; Neurosciences Department (M.A.B.), Hospital Dr. Rafael A. Calderón Guardia, CCSS, University of Costa Rica; Vascular Neurology Section (B.C.C., A.M.I.M., A.G.P., A.G.-N.), Stroke Center, Hospital General Universitario Gregorio Marañón, IiSGM Health Research Institute, Universidad Complutense de Madrid, Spain; Department of Neurology (J.P., T.T.), Helsinki University Central Hospital and University of Helsinki, Finland; Department of Clinical Neurosciences (T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (T.T.), Sahlgrenska University Hospital, Gothenburg, Sweden; Stroke Service (V.P.), Department of Neurosciences, Leeds Teaching Hospitals NHS Trust and Medical School, University of Leeds, UK; and Department of Neurology (F.B.), S. Paolo Hospital, Savona, Italy.

Objective: A tool to stratify the risk of stroke recurrence in patients with embolic stroke of undetermined source (ESUS) could be useful in research and clinical practice. We aimed to determine whether a score can be developed and externally validated for the identification of patients with ESUS at high risk for stroke recurrence.

Methods: We pooled the data of all consecutive patients with ESUS from 11 prospective stroke registries. We performed multivariable Cox regression analysis to identify predictors of stroke recurrence. Based on the coefficient of each covariate of the fitted multivariable model, we generated an integer-based point scoring system. We validated the score externally assessing its discrimination and calibration.

Results: In 3 registries (884 patients) that were used as the derivation cohort, age, leukoaraiosis, and multiterritorial infarct were identified as independent predictors of stroke recurrence and were included in the final score, which assigns 1 point per every decade after 35 years of age, 2 points for leukoaraiosis, and 3 points for multiterritorial infarcts (acute or old nonlacunar). The rate of stroke recurrence was 2.1 per 100 patient-years (95% confidence interval [CI] 1.44-3.06) in patients with a score of 0-4 (low risk), 3.74 (95% CI 2.77-5.04) in patients with a score of 5-6 (intermediate risk), and 8.23 (95% CI 5.99-11.3) in patients with a score of 7-12 (high risk). Compared to low-risk patients, the risk of stroke recurrence was significantly higher in intermediate-risk (hazard ratio [HR] 1.78, 95% CI 1.1-2.88) and high-risk patients (HR 4.67, 95% CI 2.83-7.7). The score was well-calibrated in both derivation and external validation cohorts (8 registries, 820 patients) (Hosmer-Lemeshow test χ: 12.1 [ = 0.357] and χ: 21.7 [ = 0.753], respectively). The area under the curve of the score was 0.63 (95% CI 0.58-0.68) and 0.60 (95% CI 0.54-0.66), respectively.

Conclusions: The proposed score can assist in the identification of patients with ESUS at high risk for stroke recurrence.
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http://dx.doi.org/10.1212/WNL.0000000000008571DOI Listing
December 2019

Thrombolysis in elderly stroke patients in Italy (TESPI) trial and updated meta-analysis of randomized controlled trials.

Int J Stroke 2021 01 26;16(1):43-54. Epub 2019 Oct 26.

Neurology Unit, Department of Medicine, University of Udine Medical School, Udine.

Background: Since its approval, the use of alteplase had been limited to patients aged ≤80 years.

Aims: TESPI trial had been designed to evaluate whether alteplase treatment within 3 h in patients with acute ischemic stroke aged >80 years resulted in favorable benefit/risk ratio compared with standard care. The meta-analysis of randomized controlled trials was updated to put findings in the context of all available evidence.

Methods: TESPI was a multicenter, open-label with blinded outcome evaluation, randomized, controlled trial. Main clinical endpoints were 90-day favorable functional outcome (mRS score 0-2) and mortality and symptomatic intracerebral hemorrhage. The trial was prematurely terminated for ethical reasons after publication of IST-3 trial which provided evidence of treatment benefit in elderly.

Results: Of the planned 600 patients, 191 (88 assigned to alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls (non-significant absolute difference of 5.7% for alteplase; OR 1.35, 95% CI 0.69-2.64,  = 0.381). Rates of death were non-significantly lower in the alteplase patients (18.1% vs. 26.5%); rates of symptomatic intracerebral hemorrhage were similar between the two groups (5.9% vs. 5.1%). The updated meta-analysis showed consistent results with prior estimates and add weights.

Conclusions: The effects of alteplase observed in this interrupted trial did not reach statistical significance, probably for the small numbers, but are consistent with and add weight to the sum total of the randomized evidence demonstrating that alteplase is beneficial in patients with acute ischemic stroke aged over 80 years, particularly if given within 3 h.
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http://dx.doi.org/10.1177/1747493019884525DOI Listing
January 2021

Mortality Risk in Acute Ischemic Stroke Patients With Large Vessel Occlusion Treated With Mechanical Thrombectomy.

J Am Heart Assoc 2019 11 28;8(21):e014425. Epub 2019 Oct 28.

Second Department of Neurology "Attikon" Hospital School of Medicine National and Kapodistrian University of Athens Greece.

Background Recent randomized controlled clinical trials have provided solid evidence that mechanical thrombectomy (MT) coupled with best medical therapy (BMT) improve functional outcomes of acute ischemic stroke patients with large vessel occlusion compared with BMT alone. However, they provided inconclusive evidence on the benefit of MT on mortality. Methods and Results We evaluated the association of MT+BMT compared with BMT with the risk of 3-month mortality using aggregate data from all available randomized controlled clinical trials. We also sought to identify potential predictors on the mortality risk and performed univariate meta-regression analyses. Our literature search identified 11 eligible randomized controlled clinical trials, including a total of 2460 patients. The pooled rates of 3-month mortality were 15% (95% CI:12%-19%) and 19% (95% CI:16%-23%), respectively, in the MT+BMT and BMT groups. In the overall analysis MT+BMT was associated with a significantly lower risk for 3-month mortality compared with BMT (risk ratio=0.83, 95% CI:0.69-0.99; =0.04), without heterogeneity across included studies (I=3%, for Cochran Q=0.41). No evidence of publication bias was present in funnel plot inspection and Egger statistical test (=0.762). In meta-regression analyses no moderating effect on the aforementioned association was detected with patient age (=0.254), sex (=0.702), admission systolic blood pressure (=0.601), admission glucose (=0.277), onset-to-groin puncture time (=0.985), administration of intravenous alteplase before MT (=0.804), MT under general anesthesia (=0.735), and successful reperfusion following MT (=0.663). Conclusions Our meta-analysis provides evidence that MT+BMT reduces the risk of 3-month mortality compared with BMT alone. This association appears not to be moderated by individual patient or procedural characteristics.
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http://dx.doi.org/10.1161/JAHA.119.014425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898819PMC
November 2019
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