237 results on '"Alessandro Pezzini"'
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2. Evidence of survival bias in the association between APOE-Є4 and age at ischemic stroke onset
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Joanna von Berg, Patrick F. McArdle, Paavo Häppölä, Jeffrey Haessler, Charles Kooperberg, Robin Lemmens, Alessandro Pezzini, Vincent Thijs, Sara L. Pulit, Steven J. Kittner, Braxton D. Mitchell, Jeroen de Ridder, and Sander W. van der Laan
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genome-wide association study ,stroke ,age at onset ,APOE ,atherosclerosis ,Genetics ,QH426-470 - Abstract
IntroductionLarge genome-wide association studies (GWASs) using case–control study designs have now identified tens of loci associated with ischemic stroke (IS). As a complement to these studies, we performed GWAS in a case-only design to identify loci influencing the age at onset (AAO) of ischemic stroke.MethodsAnalyses were conducted in a discovery cohort of 10,857 ischemic stroke cases using a linear regression framework. We meta-analyzed all SNPs with p-value C allele was associated with a 1.29-year earlier stroke AAO (meta p-value = 2.48 x 10−11). This APOE variant has previously been associated with increased mortality and ischemic stroke AAO. We hypothesized that the association with AAO may reflect a survival bias attributable to an age-related decrease in mortality among APOE-Є4 carriers and have no association to stroke AAO per se. A simulation study showed that a variant associated with overall mortality might indeed be detected with an AAO analysis. A variant with a 2-fold increase in mortality risk would lead to an observed effect of AAO that is comparable to what we found.DiscussionIn conclusion, we detected a robust association of the APOE locus with stroke AAO and provided simulations to suggest that this association may be unrelated to ischemic stroke per se but related to a general survival bias.
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- 2024
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3. Combining Intravenous Thrombolysis and Dual Antiplatelet Treatment in Patients With Minor Ischemic Stroke: A Propensity Matched Analysis of the READAPT Study Cohort
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Raffaele Ornello, Matteo Foschi, Federico De Santis, Michele Romoli, Tiziana Tassinari, Valentina Saia, Silvia Cenciarelli, Chiara Bedetti, Chiara Padiglioni, Bruno Censori, Valentina Puglisi, Luisa Vinciguerra, Maria Guarino, Valentina Barone, Marialuisa Zedde, Ilaria Grisendi, Marina Diomedi, Maria Rosaria Bagnato, Marco Petruzzellis, Domenico Maria Mezzapesa, Pietro Di Viesti, Vincenzo Inchingolo, Manuel Cappellari, Cecilia Zivelonghi, Paolo Candelaresi, Vincenzo Andreone, Giuseppe Rinaldi, Alessandra Bavaro, Anna Cavallini, Stefan Moraru, Pietro Querzani, Valeria Terruso, Marina Mannino, Alessandro Pezzini, Giovanni Frisullo, Francesco Muscia, Maurizio Paciaroni, Maria Giulia Mosconi, Andrea Zini, Ruggiero Leone, Carmela Palmieri, Letizia Maria Cupini, Michela Marcon, Rossana Tassi, Enzo Sanzaro, Cristina Paci, Giovanna Viticchi, Daniele Orsucci, Anne Falcou, Simone Beretta, Roberto Tarletti, Patrizia Nencini, Eugenia Rota, Federica Nicoletta Sepe, Delfina Ferrandi, Luigi Caputi, Gino Volpi, Salvatore La Spada, Mario Beccia, Claudia Rinaldi, Vincenzo Mastrangelo, Francesco Di Blasio, Paolo Invernizzi, Giuseppe Pelliccioni, Maria Vittoria De Angelis, Laura Bonanni, Giampietro Ruzza, Emanuele Alessandro Caggia, Monia Russo, Agnese Tonon, Maria Cristina Acciarri, Sabrina Anticoli, Cinzia Roberti, Giovanni Manobianca, Gaspare Scaglione, Francesca Pistoia, Alberto Fortini, Antonella De Boni, Alessandra Sanna, Alberto Chiti, Leonardo Barbarini, Marcella Caggiula, Maela Masato, Massimo Del Sette, Francesco Passarelli, Maria Roberta Bongioanni, Danilo Toni, Stefano Ricci, Eleonora De Matteis, and Simona Sacco
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dual antiplatelet treatment ,functional outcome ,intravenous thrombolysis ,ischemic stroke ,real world ,safety ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background The optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS. Methods and Results This is a prespecified propensity score‐matched analysis from a prospective multicentric real‐world study (READAPT [Real‐Life Study on Short‐Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]). We included patients with MIS (National Institutes of Health Stroke Scale score at admission ≤5), without prestroke disability (modified Rankin scale [mRS] score ≤2). The primary outcomes were 90‐day mRS score of 0 to 2 and ordinal mRS distribution. The secondary outcomes included 90‐day risk of stroke and other vascular events and 24‐hour early neurological improvement or deterioration (≥2‐point National Institutes of Health Stroke Scale score decrease or increase from the baseline, respectively). From 1373 patients with MIS, 240 patients treated with IVT plus DAPT were matched with 427 patients treated with DAPT alone. At 90 days, IVT plus DAPT versus DAPT alone showed similar frequency of mRS 0 to 2 (risk difference, 2.3% [95% CI −2.0% to 6.7%]; P=0.295; risk ratio, 1.03 [95% CI 0.98–1.08]; P=0.312) but more favorable ordinal mRS scores distribution (odds ratio, 0.57 [95% CI 0.41–0.79]; P
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- 2024
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4. The balance between hemorrhage and thrombosis in patients surviving spontaneous intracerebral bleeding: the nightmare of a neurologist
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Alessandro Pezzini
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Intracerebral hemorrhage ,thrombosis ,antithrombotic ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
With approximately 3 million people worldwide affected each year and the highly associated mortality and morbidity, intracerebral hemorrhage is the stroke subtype with the most severe clinical consequences. This is mainly due, on the one hand, to the lack of specific acute treatments, as opposed to the ischemic counterpart of stroke, on the other hand, to the occurrence of further vascular events after the index bleeding [...].
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- 2024
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5. Corrigendum: Tandem occlusions involving the internal carotid and anterior cerebral arteries—A rare form of stroke: results from the multicenter EVATRISP collaboration study
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Andrei Filioglo, Naaem Simaan, Asaf Honig, Mirjam Heldner, Alessandro Pezzini, Nicolas Martinez-Majander, Visnja Padjen, Philipp Baumgartner, Panagiotis Papanagiotou, Alexander Salerno, Christian Nolte, Annika Nordanstig, Stefan Engelter, Andrea Zini, Marialuisa Zedde, João Pedro Marto, Marcel Arnold, Mauro Magoni, Henrik Gensicke, Jose Cohen, and Ronen Leker
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cerebrovascular disease ,endovascular ,stroke ,thrombectomy ,anterior cerebral artery ,Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2024
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6. Recanalization Therapies for Large Vessel Occlusion Due to Cervical Artery Dissection: A Cohort Study of the EVA-TRISP Collaboration
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Christopher Traenka, Johannes Lorscheider, Christian Hametner, Philipp Baumgartner, Jan Gralla, Mauro Magoni, Nicolas Martinez-Majander, Barbara Casolla, Katharina Feil, Rosario Pascarella, Panagiotis Papanagiotou, Annika Nordanstig, Visnja Padjen, Carlo W. Cereda, Marios Psychogios, Christian H. Nolte, Andrea Zini, Patrik Michel, Yannick Béjot, Andreas Kastrup, Marialuisa Zedde, Georg Kägi, Lars Kellert, Hilde Henon, Sami Curtze, Alessandro Pezzini, Marcel Arnold, Susanne Wegener, Peter Ringleb, Turgut Tatlisumak, Paul J. Nederkoorn, Stefan T. Engelter, and Henrik Gensicke
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cervical artery dissection ,stroke ,endovascular treatment ,thrombolysis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background and Purpose This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD). Methods This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015–2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included. Primary outcome measures were (1) favorable 3-month outcome (modified Rankin Scale score 0–2) and (2) complete recanalization (thrombolysis in cerebral infarction scale 2b/3). Odds ratios with 95% confidence intervals (OR [95% CI]) from logistic regression models were calculated (unadjusted, adjusted). Secondary analyses were performed in the patients with LVO in the anterior circulation (LVOant) including propensity score matching. Results Among 290 patients, 222 (76.6%) had EVT and 68 (23.4%) IVT alone. EVT-treated patients had more severe strokes (National Institutes of Health Stroke Scale score, median [interquartile range]: 14 [10–19] vs. 4 [2–7], P
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- 2023
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7. Spontaneous cervical artery dissection: is it really a connective tissue disease? A comprehensive review
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Muhammed Enes Gunduz, Ramanathan Kadirvel, David F. Kallmes, Alessandro Pezzini, and Zafer Keser
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cervical artery dissection ,skin biopsy ,connective tissue disorder ,genetics ,stroke ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
BackgroundSpontaneous cervical artery dissection (sCeAD) is an important cause of stroke in young adults. The underlying pathophysiology remains unclear, without validated biomarkers to identify subjects at risk. Previous studies suggested the role of abnormalities in the connective component of the arterial wall.PurposeTo assess dermal ultrastructural aberrations of connective tissue by skin biopsy and genetic variations in sCeAD patients.MethodWe searched the PubMed and Scopus databases until August 2023 with PRISMA guidelines. Original articles assessing skin biopsy in sCeAD patients were included. Two reviewers independently conducted the screening.FindingsWe included 16 studies compromising 459 patients. Thirteen studies assessed ultrastructural changes and found aberrations of collagen and elastic fibers, described as irregular contours and calibers of collagen fibrils, composite flower-like fibrils, fragmented moth-eaten elastin, and microcalcifications, cumulatively in 50.5% of patients. Seven studies showed no causative mutations in collagen type I, III, V, or elastin genes. One study showed linkage between connective tissue alterations and mutation on chromosomes 15q2 and 10q26 using genome-wide linkage analysis, while another study found significant copy number variant enrichments in genes involved in extracellular matrix (COL5A2/COL3A1/SNTA1) and collagen fibril organizations (COL5A2/COL3A1). Finally, differential expression of extracellular proteins was linked to connective tissue disorder in patients with recurrent sCeAD using a quantitative proteomics approach.ConclusionCurrent literature supports the hypothesis that an underlying, subclinical connective tissue disorder, likely genetically determined, may predispose to arterial wall weakness and sCeAD. Further studies with larger sample sizes and robust methodology are needed to better define the role of connective tissue in sCeAD pathogenesis.
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- 2023
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8. Characteristics of Early Presenters after Intracerebral Hemorrhage
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Andrea Morotti, Jawed Nawabi, Frieder Schlunk, Loris Poli, Paolo Costa, Federico Mazzacane, Giorgio Busto, Elisa Scola, Francesco Arba, Laura Brancaleoni, Sebastiano Giacomozzi, Luigi Simonetti, Michele Laudisi, Anna Cavallini, Massimo Gamba, Mauro Magoni, Roberto Gasparotti, Alessandro Padovani, Alessandro Pezzini, Andrea Zini, Enrico Fainardi, and Ilaria Casetta
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2022
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9. Tandem occlusions involving the internal carotid and anterior cerebral arteries—A rare form of stroke: Results from the multicenter EVATRISP collaboration study
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Andrei Filioglo, Naaem Simaan, Asaf Honig, Mirjam Heldner, Alessandro Pezzini, Nicolas Martinez-Majander, Visnja Padjen, Philipp Baumgartner, Panagiotis Papanagiotou, Alexander Salerno, Christian Nolte, Annika Nordanstig, Stefan Engelter, Andrea Zini, Marialuisa Zedde, João Pedro Marto, Marcel Arnold, Mauro Magoni, Henrik Gensicke, Jose Cohen, and Ronen Leker
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cerebrovascular disease ,endovascular ,stroke ,thrombectomy ,anterior cerebral artery ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
BackgroundPatients with stroke secondary to isolated anterior cerebral artery (ACA) occlusions have poor outcomes. Whether tandem occlusions (TO) of the extracranial internal carotid (ICA) and the ACA carry even worse outcomes that remain unknown.MethodsPatients with TO involving ICA and ACA occlusions were identified from 14 participating centers from the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) project which is a multicenter, observational, cohort study with prospective accrual of data followed by retrospective data analysis. Patients with isolated ACA stroke served as controls.ResultsIncluded were 92 patients with isolated ACA and 16 patients with ICA-ACA TO stroke. On univariate analyses, patients with TO had more severe strokes on admission [median NIHSS (IQR) 13.5 (9–21) vs. 8 (5–12), p = 0.003] and were more often treated with thrombectomy (81 vs. 40%, p = 0.002). Mortality rates were higher among TO patients (31 vs. 11%, p = 0.03). Rates of favorable functional outcomes were numerically lower among TO patients (38 vs. 60%) but the difference was not statistically significant (p = 0.09). On multivariate analyses, the presence of TO did not modify the chances for favorable outcomes.ConclusionTO stroke with ICA and isolated ACA involvement is rare and results in more severe initial neurological deficits and higher mortality compared to those seen in patients with isolated ACA stroke.
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- 2022
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10. Editorial: Migraine and vascular disorders
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Alessandro Pezzini
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migraine ,stroke ,vascular disease ,cerebral vascular accident ,migraine with aura ,Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2022
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11. EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry
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Charles B L M Majoie, Martin Bendszus, Patrik Michel, Marcel Arnold, Jan Gralla, Urs Fischer, Jan F Scheitz, Didier Leys, Peter Arthur Ringleb, Daniel Strbian, David J Seiffge, Panagiotis Papanagiotou, George Ntaios, Andreas Kastrup, Ronen R Leker, José E Cohen, Nicolas Bricout, Alex Brehm, Hilde Henon, Zsolt Kulcsar, Turgut Tatlisumak, Alexandros Rentzos, Katarina Jood, Nicolas Martinez-Majander, Alessandro Pezzini, Ashraf Eskandari, Jan Liman, Katharina Feil, Lars Kellert, Markus Möhlenbruch, Georg Bohner, Marios Psychogios, Mauro Magoni, Annika Nordanstig, Andrea Zini, Henrik Gensicke, Sanne M Zinkstok, Sami Curtze, Christian Hametner, Visnja Padjen, Susanne Wegener, Georg Kägi, Christian H Nolte, Jan-Erik Karlsson, Camilla Karlsson, Christopher Traenka, Hebun Erdur, Johannes Weber, Stefan Engelter, Gerli Sibolt, Philippe Lyrer, Merih I Baharoglu, Hakan Sarikaya, Dejana R Jovanovic, Andreas Luft, Kimmo Lappalainen, John Gomori, Ivan Vukasinovic, Vladimir Cvetic, Eftychia Kapsalaki, and Paul J J Nederkoorn
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Medicine - Abstract
Purpose The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.Participants All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Findings to date Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.Future plans This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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- 2021
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12. History of Migraine and Volume of Brain Infarcts: The Italian Project on Stroke at Young Age (IPSYS)
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Valeria De Giuli, Michele Besana, Mario Grassi, Marialuisa Zedde, Andrea Zini, Corrado Lodigiani, Simona Marcheselli, Anna Cavallini, Giuseppe Micieli, Maurizia Rasura, Maria Luisa DeLodovici, Giampaolo Tomelleri, Nicoletta Checcarelli, Alberto Chiti, Elisa Giorli, Massimo Del Sette, Lucia Tancredi, Antonella Toriello, Massimiliano Braga, Andrea Morotti, Loris Poli, Filomena Caria, Massimo Gamba, Rosalba Patella, Alessandra Spalloni, Anna Maria Simone, Rosario Pascarella, Sandro Beretta, Enrico Fainardi, Alessandro Padovani, Roberto Gasparotti, and Alessandro Pezzini
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brain ischemia ,cortical spreading depression ,migraine disorders ,risk factors ,stroke ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background and Purpose Migraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated. Methods In a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status. Results A cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm3 [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm3 [IQR, 0.8 to 10.1], P
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- 2019
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13. Intravenous fibrinolysis plus endovascular thrombectomy versus direct endovascular thrombectomy for anterior circulation acute ischemic stroke: clinical and infarct volume results
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Massimo Gamba, Nicola Gilberti, Enrico Premi, Angelo Costa, Michele Frigerio, Dikran Mardighian, Veronica Vergani, Raffaella Spezi, Ilenia Delrio, Andrea Morotti, Loris Poli, Valeria De Giuli, Filomena Caria, Alessandro Pezzini, Roberto Gasparotti, Alessandro Padovani, and Mauro Magoni
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Ischemic stroke ,Intravenous thrombolysis ,Endovascular therapy ,Combined therapy ,Large vessels occlusion ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background endovascular therapy (ET) is the standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). The role of adjunctive intravenous thrombolysis (IVT) in these patients remains unclear. The present study aims to investigate whether IVT followed by ET (CoT, combined therapy) provides additional benefits over direct ET for anterior circulation AIS with LVO. Methods we achieved a single center retrospective study of patients with AIS caused by anterior circulation LVO, referred to our center between January 2014 and January 2017 and treated with ET. Functional recovery (modified Rankin at 3-months follow-up), recanalization rate (thrombolysis in cerebral infarction [TICI] score) and time, early follow-up brain CT scan infarct volume (EFIV) (for recanalized patients only), symptomatic intracerebral hemorrhage (sICH) and 3-month mortality were the outcomes of interests. Independent predictors of the outcomes were explored with multivariable logistic regression. Results 145 subjects were included in the study, of whom 70 underwent direct ET and 75 were treated with CoT. Functional independence at 3-months was more frequent in CoT subjects compared to patients who received direct ET (mRS score 0–1: 48.5% vs 18.6%; P
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- 2019
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14. Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19
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Kuaikuai Duan, Enrico Premi, Andrea Pilotto, Viviana Cristillo, Alberto Benussi, Ilenia Libri, Marcello Giunta, H. Jeremy Bockholt, Jingyu Liu, Riccardo Campora, Alessandro Pezzini, Roberto Gasparotti, Mauro Magoni, Alessandro Padovani, and Vince D. Calhoun
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COVID-19 ,Computed tomography ,Gray matter volume ,Frontal-temporal network ,Source-based morphometry ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
COVID-19, the infectious disease caused by the most recently discovered severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global pandemic. It dramatically affects people's health and daily life. Neurological complications are increasingly documented for patients with COVID-19. However, the effect of COVID-19 on the brain is less studied, and existing quantitative neuroimaging analyses of COVID-19 were mainly based on the univariate voxel-based morphometry analysis (VBM) that requires corrections for a large number of tests for statistical significance, multivariate approaches that can reduce the number of tests to be corrected have not been applied to study COVID-19 effect on the brain yet. In this study, we leveraged source-based morphometry (SBM) analysis, a multivariate extension of VBM, to identify changes derived from computed tomography scans in covarying gray matter volume patterns underlying COVID-19 in 120 neurological patients (including 58 cases with COVID-19 and 62 patients without COVID-19 matched for age, gender and diseases). SBM identified that lower gray matter volume (GMV) in superior/medial/middle frontal gyri was significantly associated with a higher level of disability (modified Rankin Scale) at both discharge and six months follow-up phases even when controlling for cerebrovascular diseases. GMV in superior/medial/middle frontal gyri was also significantly reduced in patients receiving oxygen therapy compared to patients not receiving oxygen therapy. Patients with fever presented significant GMV reduction in inferior/middle temporal gyri and fusiform gyrus compared to patients without fever. Patients with agitation showed GMV reduction in superior/medial/middle frontal gyri compared to patients without agitation. Patients with COVID-19 showed no significant GMV differences from patients without COVID-19 in any brain region. Results suggest that COVID-19 may affect the frontal-temporal network in a secondary manner through fever or lack of oxygen.
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- 2021
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15. Cervical Artery Dissection and Sports
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Stefan T. Engelter, Christopher Traenka, Caspar Grond-Ginsbach, Tobias Brandt, Maani Hakimi, Bradford B. Worrall, Stephanie Debette, Alessandro Pezzini, Didier Leys, Turgut Tatlisumak, Christian H. Nolte, and Philippe Lyrer
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cervical artery dissection ,carotid artery dissection ,vertebral artery dissection ,sport ,physical acitivity ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Cervical artery dissection (CeAD) occurring in the context of sports is a matter of concern for CeAD patients. They seek advice on the role of sports in CeAD and on the safety of resuming sports after CeAD. The scarcity of studies and guidelines addressing these issues poses a challenge. We aimed at summarizing the current knowledge about CeAD and sports in order to provide an informed, comprehensive opinion for counseling CeAD patients. We took into account pathophysiological considerations, observations of cases reports, series, and registries, and conclusions by analogy from aortic dissection or inherited connective tissue syndromes. In summary, practicing active sports as the cause of CeAD seems uncommon. It seems recommendable to refrain from any kind of sports activities for at least 1 month, which can be extended in case of an unfavorable clinical or neurovascular course. We recommend starting with sport activities at low intensity—preferably with types of endurance sports—and to gradually increase the pace in an individually tailored manner, taking into circumstances of the occurrences of the CeAD in the individual patient (particularly in relation to sports), the meaning of sports activities for the individual well-being, the presence or absence of comorbidities and of neurological sequela, neurovascular findings, and whether there are signs of an underlying connective tissue alteration. Major limitations and several forms of bias are acknowledged. Still, in the absence of any better data, the summarized observations and considerations might help clinicians in advising and counseling patients with CeAD in clinical practice.
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- 2021
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16. Pathophysiological Mechanisms and Potential Therapeutic Targets in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)
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Martina Locatelli, Alessandro Padovani, and Alessandro Pezzini
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CADASIL ,small-vessel disease ,vascular cognitive impairment ,stroke ,ischemic ,migraine with aura ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), is a hereditary small-vessels angiopathy caused by mutations in the NOTCH 3 gene, located on chromosome 19, usually affecting middle-ages adults, whose clinical manifestations include migraine with aura, recurrent strokes, mood disorders, and cognitive impairment leading to dementia and disability. In this review, we provide an overview of the current knowledge on the pathogenic mechanisms underlying the disease, focus on the corresponding therapeutic targets, and discuss the most promising treatment strategies currently under investigations. The hypothesis that CADASIL is an appropriate model to explore the pathogenesis of sporadic cerebral small vessel disease is also reviewed.
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- 2020
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17. Comparison of the Effect of Tanacethum Parthenium, 5-Hydroxy Tryptophan, and Magnesium (Aurastop) versus Magnesium Alone on Aura Phenomenon and Its Evolution
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Giorgio Dalla Volta, Paola Zavarise, Laura Perego, Lidia Savi, and Alessandro Pezzini
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Medicine (General) ,R5-920 - Abstract
None of the clinical trials on migraine conducted thus far have focused on the possibility to modulate the phenomenon of aura. Furthermore, whether proper management of aura results in a better control of the headache phase has been poorly investigated. In the setting of a single-center, pilot, clinical trial, we aimed at comparing the effects of Aurastop (a combination of tanacetum parthenium (150 mg extracted at 0.8% = 1.2 mg di of active parthenolide), griffonia simplicifoila (20 mg of 5-hydroxy tryptophan), and magnesium (185 mg of magnesium pidolatum)) with those of magnesium alone (2.25 grams/tablet, corresponding to 184 mg of Mg++) in the treatment of acute attacks of migraine with aura. Between June 2017 and June 2018, 50 consecutive patients (27/23 male/female; mean age, 31 [18–57] years) with at least 3 episodes of aura per year were included (t0). Participants were instructed to keep track of the following 4 episodes of migraine with aura (t1) and invited to assume (1) a tablet of Aurastop at the beginning of the following 2 episodes of aura and (2) a magnesium tablet alone at the occurrence of the third and fourth aura attacks. Forty-eight patients (96.0%) had >50% reduction in aura duration when treated with Aurastop vs. 7 patients (14.0%) when treated with magnesium alone (p50% reduction of aura-related disability when receiving Aurastop vs. 5 patients (10.0%) when treated with magnesium alone (p
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- 2019
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18. Vascular Remodeling in Moyamoya Angiopathy: From Peripheral Blood Mononuclear Cells to Endothelial Cells
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Francesca Tinelli, Sara Nava, Francesco Arioli, Gloria Bedini, Emma Scelzo, Daniela Lisini, Giuseppe Faragò, Andrea Gioppo, Elisa F. Ciceri, Francesco Acerbi, Paolo Ferroli, Ignazio G. Vetrano, Silvia Esposito, Veronica Saletti, Chiara Pantaleoni, Federica Zibordi, Nardo Nardocci, Maria Luisa Zedde, Alessandro Pezzini, Vincenzo Di Lazzaro, Fioravante Capone, Maria Luisa Dell’Acqua, Peter Vajkoczy, Elisabeth Tournier-Lasserve, Eugenio A. Parati, Anna Bersano, and Laura Gatti
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neovascularization ,Moyamoya angiopathy ,endothelial progenitor cells ,RNF213 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The pathophysiological mechanisms of Moyamoya angiopathy (MA), which is a rare cerebrovascular condition characterized by recurrent ischemic/hemorrhagic strokes, are still largely unknown. An imbalance of vasculogenic/angiogenic mechanisms has been proposed as one possible disease aspect. Circulating endothelial progenitor cells (cEPCs) have been hypothesized to contribute to vascular remodeling of MA, but it remains unclear whether they might be considered a disease effect or have a role in disease pathogenesis. The aim of the present study was to provide a morphological, phenotypical, and functional characterization of the cEPCs from MA patients to uncover their role in the disease pathophysiology. cEPCs were identified from whole blood as CD45dimCD34+CD133+ mononuclear cells. Morphological, biochemical, and functional assays were performed to characterize cEPCs. A significant reduced level of cEPCs was found in blood samples collected from a homogeneous group of adult (mean age 46.86 ± 11.7; 86.36% females), Caucasian, non-operated MA patients with respect to healthy donors (HD; p = 0.032). Since no difference in cEPC characteristics and functionality was observed between MA patients and HD, a defective recruitment mechanism could be involved in the disease pathophysiology. Collectively, our results suggest that cEPC level more than endothelial progenitor cell (EPC) functionality seems to be a potential marker of MA. The validation of our results on a larger population and the correlation with clinical data as well as the use of more complex cellular model could help our understanding of EPC role in MA pathophysiology.
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- 2020
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19. Hemorrhagic Transformation in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Time to Initiation of Oral Anticoagulant Therapy and Outcomes
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Maurizio Paciaroni, Fabio Bandini, Giancarlo Agnelli, Georgios Tsivgoulis, Shadi Yaghi, Karen L. Furie, Prasanna Tadi, Cecilia Becattini, Marialuisa Zedde, Azmil H. Abdul‐Rahim, Kennedy R. Lees, Andrea Alberti, Michele Venti, Monica Acciarresi, Cataldo D'Amore, Maria Giulia Mosconi, Ludovica Anna Cimini, Riccardo Altavilla, Giacomo Volpi, Paolo Bovi, Monica Carletti, Alberto Rigatelli, Manuel Cappellari, Jukka Putaala, Liisa Tomppo, Turgut Tatlisumak, Simona Marcheselli, Alessandro Pezzini, Loris Poli, Alessandro Padovani, Luca Masotti, Vieri Vannucchi, Sung‐Il Sohn, Gianni Lorenzini, Rossana Tassi, Francesca Guideri, Maurizio Acampa, Giuseppe Martini, George Ntaios, George Athanasakis, Konstantinos Makaritsis, Efstathia Karagkiozi, Konstantinos Vadikolias, Chrissoula Liantinioti, Maria Chondrogianni, Nicola Mumoli, Domenico Consoli, Franco Galati, Simona Sacco, Antonio Carolei, Cindy Tiseo, Francesco Corea, Walter Ageno, Marta Bellesini, Giovanna Colombo, Giorgio Silvestrelli, Alfonso Ciccone, Alessia Lanari, Umberto Scoditti, Licia Denti, Michelangelo Mancuso, Miriam Maccarrone, Leonardo Ulivi, Giovanni Orlandi, Nicola Giannini, Gino Gialdini, Tiziana Tassinari, Maria Luisa De Lodovici, Giorgio Bono, Christina Rueckert, Antonio Baldi, Sebastiano D'Anna, Danilo Toni, Federica Letteri, Martina Giuntini, Enrico Maria Lotti, Yuriy Flomin, Alessio Pieroni, Odysseas Kargiotis, Theodore Karapanayiotides, Serena Monaco, Mario Maimone Baronello, Laszló Csiba, Lilla Szabó, Alberto Chiti, Elisa Giorli, Massimo Del Sette, Davide Imberti, Dorjan Zabzuni, Boris Doronin, Vera Volodina, Patrik Michel, Peter Vanacker, Kristian Barlinn, Lars‐Peder Pallesen, Jessica Barlinn, Dirk Deleu, Gayane Melikyan, Faisal Ibrahim, Naveed Akhtar, Vanessa Gourbali, and Valeria Caso
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atrial fibrillation ,hemorrhagic transformation ,stroke ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.
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- 2018
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20. Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke.
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John W Cole, Huichun Xu, Kathleen Ryan, Thomas Jaworek, Nicole Dueker, Patrick McArdle, Brady Gaynor, Yu-Ching Cheng, Jeffrey O'Connell, Steve Bevan, Rainer Malik, Naveed Uddin Ahmed, Philippe Amouyel, Sheraz Anjum, Joshua C Bis, David Crosslin, John Danesh, Stefan T Engelter, Myriam Fornage, Philippe Frossard, Christian Gieger, Anne-Katrin Giese, Caspar Grond-Ginsbach, Weang Kee Ho, Elizabeth Holliday, Jemma Hopewell, M Hussain, W Iqbal, S Jabeen, Jim Jannes, Ayeesha Kamal, Yoichiro Kamatani, Sandip Kanse, Manja Kloss, Mark Lathrop, Didier Leys, Arne Lindgren, W T Longstreth, Khalid Mahmood, Christa Meisinger, Tiina M Metso, Thomas Mosley, Martina Müller-Nurasyid, Bo Norrving, Eugenio Parati, Annette Peters, Alessandro Pezzini, I Quereshi, Asif Rasheed, A Rauf, T Salam, Jess Shen, Agnieszka Słowik, Tara Stanne, Konstantin Strauch, Turgut Tatlisumak, Vincent N Thijs, Steffen Tiedt, Matthew Traylor, Melanie Waldenberger, Matthew Walters, Wei Zhao, Giorgio Boncoraglio, Stéphanie Debette, Christina Jern, Christopher Levi, Hugh Markus, James Meschia, Arndt Rolfs, Peter Rothwell, Danish Saleheen, Sudha Seshadri, Pankaj Sharma, Cathie Sudlow, Bradford Worrall, METASTROKE Consortium of the ISGC, WTCCC-2 Consortium, O Colin Stine, Steven J Kittner, and Braxton D Mitchell
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Medicine ,Science - Abstract
Background and purposePolymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication.MethodsDiscovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15-49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r2≥0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-ageResultsAmong GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity.ConclusionPROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.
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- 2018
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21. Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin‐K Oral Anticoagulants (RAF‐NOACs) Study
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Maurizio Paciaroni, Giancarlo Agnelli, Nicola Falocci, Georgios Tsivgoulis, Kostantinos Vadikolias, Chrysoula Liantinioti, Maria Chondrogianni, Paolo Bovi, Monica Carletti, Manuel Cappellari, Marialuisa Zedde, George Ntaios, Efstathia Karagkiozi, George Athanasakis, Kostantinos Makaritsis, Giorgio Silvestrelli, Alessia Lanari, Alfonso Ciccone, Jukka Putaala, Liisa Tomppo, Turgut Tatlisumak, Azmil H. Abdul‐Rahim, Kennedy R. Lees, Andrea Alberti, Michele Venti, Monica Acciarresi, Cataldo D'Amore, Cecilia Becattini, Maria Giulia Mosconi, Ludovica Anna Cimini, Rossana Soloperto, Luca Masotti, Vieri Vannucchi, Gianni Lorenzini, Rossana Tassi, Francesca Guideri, Maurizio Acampa, Giuseppe Martini, Sung‐Il Sohn, Simona Marcheselli, Nicola Mumoli, Maria Luisa De Lodovici, Giorgio Bono, Karen L. Furie, Prasanna Tadi, Shadi Yaghi, Danilo Toni, Federica Letteri, Tiziana Tassinari, Odysseas Kargiotis, Enrico Maria Lotti, Yuriy Flomin, Michelangelo Mancuso, Miriam Maccarrone, Nicola Giannini, Fabio Bandini, Alessandro Pezzini, Loris Poli, Alessandro Padovani, Umberto Scoditti, Licia Denti, Domenico Consoli, Franco Galati, Simona Sacco, Antonio Carolei, Cindy Tiseo, Vanessa Gourbali, Giovanni Orlandi, Martina Giuntini, Alberto Chiti, Elisa Giorli, Gino Gialdini, Francesco Corea, Walter Ageno, Marta Bellesini, Giovanna Colombo, Serena Monaco, Mario Maimone Baronello, Theodore Karapanayiotides, and Valeria Caso
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acute stroke ,anticoagulants ,atrial fibrillation ,secondary prevention ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundThe optimal timing to administer non–vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and ResultsRecurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA2DS2‐VASc score >4 and less reduced renal function. Thirty‐two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke. ConclusionsIn patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.
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- 2017
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22. Ischemic Stroke during Pregnancy and Puerperium
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Elisabetta Del Zotto, Alessia Giossi, Irene Volonghi, Paolo Costa, Alessandro Padovani, and Alessandro Pezzini
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Ischemic stroke during pregnancy and puerperium represents a rare occurrence but it could be a serious and stressful event for mothers, infants, and also families. Whenever it does occur, many concerns arise about the safety of the mother and the fetus in relation to common diagnostic tests and therapies leading to a more conservative approach. The physiological adaptations in the cardiovascular system and in the coagulability that accompany the pregnant state, which are more significant around delivery and in the postpartum period, likely contribute to increasing the risk of an ischemic stroke. Most of the causes of an ischemic stroke in the young may also occur in pregnant patients. Despite this, there are specific conditions related to pregnancy which may be considered when assessing this particular group of patients such as pre-eclampsia-eclampsia, choriocarcinoma, peripartum cardiomiopathy, amniotic fluid embolization, and postpartum cerebral angiopathy. This article will consider several questions related to pregnancy-associated ischemic stroke, dwelling on epidemiological and specific etiological aspects, diagnostic issue concerning the use of neuroimaging, and the related potential risks to the embryo and fetus. Therapeutic issues surrounding the use of anticoagulant and antiplatelets agents will be discussed along with the few available reports regarding the use of thrombolytic therapy during pregnancy.
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- 2011
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23. The Migraine-Ischemic Stroke Relation in Young Adults
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Alessandro Pezzini, Elisabetta Del Zotto, Alessia Giossi, Irene Volonghi, Paolo Costa, Giorgio Dalla Volta, and Alessandro Padovani
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions.
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- 2011
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24. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity
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Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stéphanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok, Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex SF Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David CM Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth JF Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda WJH Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna MM Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin NA Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M. Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Lynn Cherkas, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Christian Kubisch, Michel D Ferrari, Andrea C Belin, Maija Wessman, Arn M J M van den Maagdenberg, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Dale R Nyholt, Masato Akiyama, Varinder S. Alg, Joseph P. Broderick, Ben M. Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M. Friedrich, Emília I. Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C. Hostettler, Henry Houlden, Juha E. Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y. Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A. Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W. M. Monique Verschuren, Robin G. Walters, David J. Werring, Cristen J. Willer, Daniel Woo, Bradford B. Worrall, Sirui Zhou, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Systems Ecology, Sociology and Social Gerontology, Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J. E., Veldink, Jan H., Ruigrok, Ynte M., Girotto, G., All-In Stroke, Hunt, Group, Cadisp, Consortium for Blood Pressure, International, Headache Genetics Consortium, International, Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, International, Utrecht University [Utrecht], Baker Heart and Diabetes Institute (AUSTRALIA), University of Melbourne, University of Oslo (UiO), Norwegian University of Science and Technology (NTNU), Oslo University Hospital [Oslo], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Tokyo (UTokyo), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Université de Genève = University of Geneva (UNIGE), Excellence Laboratory LabEx DISTALZ, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Otago [Dunedin, Nouvelle-Zélande], University of Leicester, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group: Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex Sf Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David Cm Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth Jf Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda Wjh Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna Mm Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin Na Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Masato Akiyama, Varinder S Alg, Sigrid Børte, Joseph P Broderick, Ben M Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M Friedrich, Emília I Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C Hostettler, Henry Houlden, Kristian Hveem, Juha E Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W M Monique Verschuren, Robin G Walters, David J Werring, Cristen J Willer, Daniel Woo, Bradford B Worrall, Sirui Zhou, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Admin, Oskar
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Advanced and Specialized Nursing ,Incidence ,risk assessment ,Smoking/epidemiology ,intracranial aneurysm ,genetic heterogeneity ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Risk Factors ,Intracranial Aneurysm/epidemiology ,Humans ,Subarachnoid Hemorrhage/epidemiology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,genetics ,Neurology (clinical) ,aneurysmal subarachnoid hemorrhage ,genetic ,Cardiology and Cardiovascular Medicine - Abstract
Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.
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- 2023
25. Ischaemic cerebral small vessel disease caused by adenosine deaminase 2 deficiency syndrome
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Alessia Giossi, Silvia Clara Giliani, Massimo Gamba, Paola Toniati, Mauro Magoni, and Alessandro Pezzini
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Neurology ,Neurology (clinical) - Published
- 2023
26. Aortic tortuosity in Turner syndrome is associated with larger ascending aorta
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Ranjini Srinivasan, Sujata Shanbhag, Alessandro Pezzini, Laura Olivieri, and Shaine A. Morris
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Adult ,Aortic Dissection ,Predictive Value of Tests ,Humans ,Turner Syndrome ,Female ,Prospective Studies ,Child ,Aorta ,Retrospective Studies - Abstract
Turner syndrome (TS) is associated with aortic coarctation, dissection and dilation/aneurysm. Predictors of dissection are not well delineated, making decisions regarding prophylactic root replacement challenging. In other disorders, arterial tortuosity is an imaging biomarker associated with increased risk for aortic dissection and adverse cardiovascular events. We aimed to determine if, in TS, arterial tortuosity was associated with aortic dilation or aortic events. We performed a retrospective cohort analysis of unselected women and children with TS who underwent cardiovascular magnetic resonance angiography (MRA) for a prior prospective study. We calculated tortuosity indices including vertebral artery tortuosity index, aortic arch tortuosity index, thoracic aortic tortuosity index (ATI-D), and aortic tortuosity index to the celiac artery (ATI-C). We compared tortuosity in TS patients against age and gender matched controls. We evaluated univariable and multivariable associations between the tortuosity indices and aortic root and ascending aorta size as defined by z-scores, which give a sense of how far a measurement deviates from the mean. We also studied associations between tortuosity and need for aortic root replacement or aortic dissection. Of 184 subjects, with median age 34 years, mean general aortic root z-score was 0.1 ± 1.2 and mean general ascending aortic z-score was 0.4 ± 1.5. Three patients had aortic dissection, and one had prophylactic root replacement, which all occurred prior to first MRA. Vertebral tortuosity index, ATI-D, and ATI-C all increased with age (p 0.0001) for all. ATI-C was associated with larger general ascending z-score. In multivariable analysis, ATI-C remained independently associated with larger ascending aortic z-scores. The relationship between aortic indices and surgery/dissection could not be evaluated since all were collected post-surgery/dissection. Thoracic aortic tortuosity as measured by ATI-C is independently associated with larger ascending aortic dimensions. In this population with only three aortic dissections occurring prior to imaging assessment, we could not assess for associations between aortic tortuosity and dissection. Studies including more patients with aortic dissection are needed to draw further conclusions.
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- 2022
27. Practical '1-2-3-4-Day' Rule for Starting Direct Oral Anticoagulants After Ischemic Stroke With Atrial Fibrillation: Combined Hospital-Based Cohort Study
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Shunsuke Kimura, Kazunori Toyoda, Sohei Yoshimura, Kazuo Minematsu, Masahiro Yasaka, Maurizio Paciaroni, David J. Werring, Hiroshi Yamagami, Takehiko Nagao, Shinichi Yoshimura, Alexandros Polymeris, Annaelle Zietz, Stefan T. Engelter, Bernd Kallmünzer, Manuel Cappellari, Tetsuya Chiba, Takeshi Yoshimoto, Masayuki Shiozawa, Takanari Kitazono, Masatoshi Koga, Kenichi Todo, Kazumi Kimura, Yoshiki Yagita, Eisuke Furui, Ryo Itabashi, Tadashi Terasaki, Yoshiaki Shiokawa, Teruyuki Hirano, Kenji Kamiyama, Jyoji Nakagawara, Shunya Takizawa, Kazunari Homma, Satoshi Okuda, Yasushi Okada, Keisuke Tokunaga, Tomoaki Kameda, Kazuomi Kario, Yoshinari Nagakane, Yasuhiro Hasegawa, Hisanao Akiyama, Satoshi Shibuya, Hiroshi Mochizuki, Yasuhiro Ito, Takahiro Nakashima, Hideki Matsuoka, Kazuhiro Takamatsu, Kazutoshi Nishiyama, Shoichiro Sato, Shoji Arihiro, Manabu Inoue, Masahito Takagi, Kanta Tanaka, Kazuyuki Nagatsuka, Takenori Yamaguchi, Yoichiro Hashimoto, Kiyohiro Houkin, Kazuo Kitagawa, Masayasu Matsumoto, Norio Tanahashi, Yasuo Terayama, Shinichiro Uchiyama, Etsuro Mori, Yutaka Furukawa, Takeshi Kimura, Yoshiaki Kumon, Ken Nagata, Shigeru Nogawa, Tomohiro Sakamoto, Toshinori Hirai, Kohsuke Kudo, Makoto Sasaki, Shotai Kobayashi, Toshimitsu Hamasaki, Michela Giustozzi, Monica Acciarresi, Giancarlo Agnelli, Valeria Caso, Fabio Bandini, Georgios Tsivgoulis, Shadi Yaghi, Karen L. Furie, Prasanna Tadi, Cecilia Becattini, Marialuisa Zedde, Azmil H Abdul-Rahim, Kennedy R Lees, Andrea Alberti, Michele Venti, Cataldo D’Amore, Maria Giulia Mosconi, Ludovica Anna Cimini, Paolo Bovi, Monica Carletti, Alberto Rigatelli, Jukka Putaala, Liisa Tomppo, Turgut Tatlisumak, Simona Marcheselli, Alessandro Pezzini, Loris Poli, Alessandro Padovani, Vieri Vannucchi, Sung-Il Sohn, Gianni Lorenzini, Rossana Tassi, Francesca Guideri, Maurizio Acampa, Giuseppe Martini, George Ntaios, George Athanasakis, Konstantinos Makaritsis, Efstathia Karagkiozi, Konstantinos Vadikolias, Chrissoula Liantinioti, Maria Chondrogianni, Nicola Mumoli, Franco Galati, Simona Sacco, Cindy Tiseo, Francesco Corea, Walter Ageno, Marta Bellesini, Giovanna Colombo, Giorgio Silvestrelli, Alfonso Ciccone, Alessia Lanari, Umberto Scoditti, Licia Denti, Michelangelo Mancuso, Miriam Maccarrone, Leonardo Ulivi, Giovanni Orlandi, Nicola Giannini, Tiziana Tassinari, Maria Luisa De Lodovici, Christina Rueckert, Antonio Baldi, Danilo Toni, Federica Letteri, Martina Giuntini, Enrico Maria Lotti, Yuriy Flomin, Alessio Pieroni, Odysseas Kargiotis, Theodore Karapanayiotides, Serena Monaco, Mario Maimone Baronello, Laszló Csiba, Lilla Szabó, Alberto Chiti, Elisa Giorli, Massimo Del Sette, Davide Imberti, Dorjan Zabzuni, Boris Doronin, Vera Volodina, Patrik Michel, Peter Vanacker, Kristian Barlinn, Lars-Peder Pallesen, Jessica Barlinn, Dirk Deleu, Gayane Melikyan, Faisal Ibrahim, Naveed Akhtar, Vanessa Gourbali, Luca Masotti, Adrian Parry-Jones, Chris Patterson, Christopher Price, Abduelbaset Elmarimi, Anthea Parry, Arumug Nallasivam, Azlisham Mohd Nor, Bernard Esis, David Bruce, Christine Roffe, Clare Holmes, David Cohen, David Hargroves, David Mangion, Dinesh Chadha, Djamil Vahidassr, Dulka Manawadu, Elio Giallombardo, Elizabeth Warburton, Enrico Flossman, Gunaratam Gunathilagan, Harald Proschel, Hedley Emsley, Ijaz Anwar, James Okwera, Janet Putterill, Janice O’Connell, John Bamford, John Corrigan, Jon Scott, Jonathan Birns, Karen Kee, Kari Saastamoinen, Kath Pasco, Krishna Dani, Lakshmanan Sekaran, Lillian Choy, Liz Iveson, Maam Mamun, Mahmud Sajid, Martin Cooper, Matthew Burn, Matthew Smith, Michael Power, Michelle Davis, Nigel Smyth, Roland Veltkamp, Pankaj Sharma, Paul Guyler, Paul O’Mahony, Peter Wilkinson, Prabel Datta, Prasanna Aghoram, Rachel Marsh, Robert Luder, Sanjeevikumar Meenakishundaram, Santhosh Subramonian, Simon Leach, Sissi Ispoglou, Sreeman Andole, Timothy England, Aravindakshan Manoj, Frances Harrington, Habib Rehman, Jane Sword, Julie Staals, Karim Mahawish, Kirsty Harkness, Louise Shaw, Michael McCormich, Nikola Sprigg, Syed Mansoor, Vinodh Krishnamurthy, Philippe A Lyrer, Leo H Bonati, David J Seiffge, Christopher Traenka, Nils Peters, Gian Marco De Marchis, Sebastian Thilemann, Nikolaos S Avramiotis, Henrik Gensicke, Lisa Hert, Benjamin Wagner, Fabian Schaub, Louisa Meya, Joachim Fladt, Tolga Dittrich, Urs Fisch, Bruno Bonetti, Giampaolo Tomelleri, Nicola Micheletti, Cecilia Zivelonghi, Andrea Emiliani, Kosmas Macha, Gabriela Siedler, Svenja Stoll, Ruihao Wang, Bastian Volbers, Stefan Schwab, David Haupenthal, and Luise Gaßmann
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Advanced and Specialized Nursing ,acute ischemic stroke ,Time Factors ,Administration, Oral ,Anticoagulants ,Hemorrhage ,cardioembolism ,Hospitals ,United States ,Brain Ischemia ,anticoagulation ,atrial fibrillation ,stroke prevention ,Cohort Studies ,Stroke ,Treatment Outcome ,Ischemic Attack, Transient ,Atrial Fibrillation ,Humans ,Prospective Studies ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,Ischemic Stroke - Abstract
Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.
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- 2022
28. Subclinical Vascular Brain Lesions in Young Adults With Acute Ischemic Stroke
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Valeria De Giuli, Mario Grassi, Michele Besana, Marialuisa Zedde, Andrea Zini, Corrado Lodigiani, Simona Marcheselli, Anna Cavallini, Giuseppe Micieli, Maurizia Rasura, Maria Luisa DeLodovici, Giampaolo Tomelleri, Nicoletta Checcarelli, Alberto Chiti, Elisa Giorli, Massimo Del Sette, Lucia Tancredi, Antonella Toriello, Massimiliano Braga, Andrea Morotti, Debora Pezzini, Martina Locatelli, Valentina Mazzoleni, Sonia Bonacina, Massimo Gamba, Mauro Magoni, Rosalba Patella, Alessandra Spalloni, Anna Maria Simone, Rosario Pascarella, Sandro Beretta, Alessandro Padovani, Roberto Gasparotti, Alessandro Pezzini, Nicola Gilberti, Paola Ferrazzi, Elena Banfi, Luca Librè, Elisabetta Traverso, Erika Schirinzi, Federico Carimati, Manuel Cappellari, Giampiero Locatelli, Laura Demelas, Davide Ferrario, Alessandra Persico, Giovanni Orlandi, Manuela Napoli, Claudio Moratti, and Mario Guidotti
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Adult ,Male ,medicine.medical_specialty ,Brain Ischemia ,Brain ischemia ,White matter ,Young Adult ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,Young adult ,Stroke ,Acute ischemic stroke ,Aged ,Ischemic Stroke ,Subclinical infection ,Advanced and Specialized Nursing ,business.industry ,Brain ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Cerebral Small Vessel Diseases ,Cardiology ,Brain lesions ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age. Methods: We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score. Results: Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30–3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20–3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22–4.32]). After a median follow-up of 36.0 months (25th–75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17–3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20–3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36–4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42–4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction. Conclusions: Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.
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- 2022
29. Internal carotid artery dissection in a patient with hemophilia A: a case report and literature review
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Salvatore Iacono, Roberta Baschi, Lucia Di Giorgi, Cesare Gagliardo, Alessandro Pezzini, Roberto Monastero, Iacono, Salvatore, Baschi, Roberta, Di Giorgi, Lucia, Gagliardo, Cesare, Pezzini, Alessandro, and Monastero, Roberto
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Psychiatry and Mental health ,Settore MED/26 - Neurologia ,Neurology (clinical) ,Dermatology ,General Medicine ,Hemophilia ,Antithrombotic drugs ,Cervical artery dissection ,Neck trauma - Abstract
Spontaneous cervical artery dissection (sCeAD) is the most common cause of ischemic stroke at a young age, but its pathogenetic mechanism and risk factors are not fully elucidated. It is reasonable to think that bleeding propensity, vascular risk factors such as hypertension and head or neck trauma, and constitutional weakness of the arterial wall together play a role in the pathogenesis of sCeAD. Hemophilia A is known to be an X-linked condition that leads to spontaneous bleeding in various tissues and organs. To date, a few cases of acute arterial dissection in patients with hemophilia have been reported, but the relationship between these two diseases has not been studied so far. In addition, there are no guidelines indicating the best antithrombotic treatment option in these patients. We report the case of a man with hemophilia A who developed sCeAD and transient oculo-pyramidal syndrome and was treated with acetylsalicylic acid. We also review previous published cases of arterial dissection in patients with hemophilia, discussing the potential pathogenetic mechanism underlying this rare association and potential antithrombotic therapeutic options.
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- 2023
30. Age of onset of cerebral venous thrombosis
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Redoy Ranjan, Gie Ken-Dror, Ida Martinelli, Elvira Grandone, Sini Hiltunen, Erik Lindgren, Maurizio Margaglione, Veronique Le Cam Duchez, Aude Bagan Triquenot, Marialuisa Zedde, Michelangelo Mancuso, Ynte M Ruigrok, Brad Worrall, Jennifer J Majersik, Jukka Putaala, Elena Haapaniemi, Susanna M Zuurbier, Matthijs C Brouwer, Serena M Passamonti, Maria Abbattista, Paolo Bucciarelli, Robin Lemmens, Emanuela Pappalardo, Paolo Costa, Marina Colombi, Diana Aguiar de Sousa, Sofia Rodrigues, Patrícia Canhao, Aleksander Tkach, Rosa Santacroce, Giovanni Favuzzi, Antonio Arauz, Donatella Colaizzo, Kostas Spengos, Amanda Hodge, Reina Ditta, Thang S Han, Alessandro Pezzini, Jonathan M Coutinho, Vincent Thijs, Katarina Jood, Turgut Tatlisumak, José M Ferro, Pankaj Sharma, Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, ACS - Atherosclerosis & ischemic syndromes, and ANS - Neurovascular Disorders
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age of onset ,Cerebral venous thrombosis ,Original Research Articles ,Neurology (clinical) ,women ,Cardiology and Cardiovascular Medicine ,cerebral venous sinus thrombosis - Abstract
Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset. Methods: We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observational study on CVT. Composite factors analysis (CFA) was performed to determine the impact on the age of CVT onset in males and females. Results: A total of 1309 CVT patients (75.3% females) aged ⩾18 years were recruited. The overall median (IQR-interquartile range) age for males and females was 46 (35–58) years and 37 (28–47) years ( p Conclusions: Women suffer CVT 9 years earlier in comparison to men. Female patients with multiple (⩾1) risk factors suffer CVT ~12 years earlier compared to those with no identifiable risk factors.
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- 2023
31. Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration
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Valerian L, Altersberger, Norman, Rusche, Nicolas, Martinez-Majander, Christian, Hametner, Jan F, Scheitz, Hilde, Henon, Maria Luisa, Dell'Acqua, Davide, Strambo, Jeffrey, Stolp, Mirjam R, Heldner, Ilaria, Grisendi, Dejana R, Jovanovic, Yannick, Bejot, Alessandro, Pezzini, Ronen R, Leker, Georg, Kägi, Susanne, Wegener, Carlo W, Cereda, Erik, Lindgren, George, Ntaios, Ines, Piot, Alexandros A, Polymeris, Philippe A, Lyrer, Silja, Räty, Gerli, Sibolt, Marjaana, Tiainen, Miriam, Heyse, Hebun, Erdur, Olfa, Kaaouana, Visnja, Padjen, Marialuisa, Zedde, Marcel, Arnold, Paul J, Nederkoorn, Patrik, Michel, Guido, Bigliardi, Andrea, Zini, Charlotte, Cordonnier, Christian H, Nolte, Peter A, Ringleb, Sami, Curtze, Stefan T, Engelter, Henrik, Gensicke, Neurology, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Neuroscience - Neurovascular Disorders
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Advanced and Specialized Nursing ,Aged, 80 and over ,registries ,survivors ,Brain Ischemia ,Cohort Studies ,Stroke ,Treatment Outcome ,Fibrinolytic Agents ,Humans ,Thrombolytic Therapy ,Neurology (clinical) ,Prospective Studies ,Cardiology and Cardiovascular Medicine ,Intracranial Hemorrhages ,intracranial hemorrhage ,Aged ,Ischemic Stroke - Abstract
Background: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. Methods: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those Results: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratio adjusted 1.14 [0.83–1.57]) did not differ significantly between both groups. However, the probability of death (odds ratio adjusted 3.77 [3.14–4.53]) and poor functional outcome (odds ratio adjusted 2.63 [2.13–3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. Conclusions: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.
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- 2022
32. Age-dependent effect of susceptibility factors on the risk of intracerebral haemorrhage: Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy)
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Martina Locatelli, Rosa Musolino, Monica Acciarresi, Paolo La Spina, Valentina Saba, Sonia Bonacina, Mauro Magoni, Cristiano Azzini, Mario Grassi, Giovanni de Gaetano, Debora Pezzini, Cinzia Finocchi, Alessandro De Vito, Giampaolo Tomelleri, Domenico Marco Bonifati, Augusto Di Castelnuovo, Giorgio Silvestrelli, Massimo Del Sette, Francesco Grillo, Simona Marcheselli, Corrado Lodigiani, Alfonso Ciccone, Marialuisa Zedde, Andrea Zini, Lucia Princiotta Cariddi, Rocco Salvatore Calabrò, Andrea Morotti, Alessandro Pezzini, Carlo Gandolfo, Marco Ritelli, Massimo Gamba, Licia Iacovello, Anna Cavallini, Giuseppe Martini, Maurizio Paciaroni, Marina Colombi, Maria Luisa DeLodovici, Alberto Chiti, Alessia Giossi, Rossana Tassi, Valentina Mazzoleni, Alessandro Padovani, and Antonella Toriello
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Male ,Risk ,medicine.medical_specialty ,Databases, Factual ,Age dependent ,030204 cardiovascular system & hematology ,Logistic regression ,cerebrovascular ,stroke ,Stroke risk ,Databases ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,80 and over ,medicine ,Humans ,Stroke ,Factual ,Aged ,Cerebral Hemorrhage ,Aged, 80 and over ,business.industry ,Incidence ,Age Factors ,Middle Aged ,medicine.disease ,Case-Control Studies ,Female ,Italy ,Psychiatry and Mental health ,Quartile ,Multicenter study ,Surgery ,Alcohol intake ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveTo investigate the age-dependent impact of traditional stroke risk factors on the occurrence of intracerebral haemorrhage (ICH).MethodsWe performed a case–control analysis, comparing consecutive patients with ICH with age-matched and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy) between 2002 and 2014 by multivariable logistic regression model within subgroups stratified by age quartiles (Q1–Q4).ResultsWe analysed 3492 patients and 3492 controls. The impact of untreated hypertension on the risk of ICH was higher in the lower than in the upper age quartile (OR 11.64, 95% CI 7.68 to 17.63 in Q1 vs OR 6.05, 95% CI 3.09 to 11.85 in Q4 with intermediate ORs in Q2 and Q3), while the opposite trend was observed for untreated hypercholesterolaemia (OR 0.63, 95% CI 0.45 to 0.97 in Q1 vs OR 0.36, 95% CI 0.26 to 0.56 in Q4 with intermediate ORs in Q2 and Q3). The effect of untreated diabetes and excessive alcohol intake was detected only in the older age group (OR 3.63, 95% CI 1.22 to 10.73, and OR 1.69, 95% CI 1.13 to 2.51, respectively).ConclusionsOur findings provide evidence of age-dependent differences in the effects of susceptibility factors on the risk of ICH.
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- 2021
33. Cervical Artery Dissections: Etiopathogenesis and Management
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Zafer Keser, Chia-Chun Chiang, John C Benson, Alessandro Pezzini, and Giuseppe Lanzino
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Stroke ,Vertebral Artery Dissection ,Risk Factors ,Endocrinology, Diabetes and Metabolism ,Public Health, Environmental and Occupational Health ,Headache ,Humans ,Pharmacology (medical) ,Hematology ,General Medicine ,Cardiology and Cardiovascular Medicine - Abstract
Cervical Artery Dissection (CeAD) is a frequent stroke etiology for patients younger than 50 years old. The most common immediate complications related to CeAD are headache and neck pain (65-95%), TIA/ischemic stroke (50%), and partial Horner's syndrome (25%). The prevailing hypothesis regarding the pathogenesis of sCeAD is that the underlying constitutional vessel wall weakness of patients with sCeAD is genetically determined and that environmental factors could act as triggers. The stroke prevention treatment of CeAD remains controversial, involving anticoagulation or antiplatelet therapy and potentially emergent stenting and/or thrombectomy or angioplasty for selected cases of carotid artery dissection with occlusion. The treatment of headache associated with CeAD depends on the headache phenotype and comorbidities. Radiographically, more than 75% of CeAD cases present with occlusion or non-occlusive stenosis. Many patients demonstrate partial and complete healing, more commonly in the carotid arteries. One-fifth of the patients develop dissecting pseudoaneurysm, but this is a benign clinical entity with an extremely low rupture and stroke recurrence risk. Good recovery is achieved in many CeAD cases, and mortality remains low. Family history of CeAD, connective tissue disorders like Ehlers-Danlos syndrome type IV, and fibromuscular dysplasia are risk factors for recurrent CeAD, which can occur in 3-9% of the cases. This review serves as a comprehensive, updated overview of CeAD, emphasizing etiopathogenesis and management.
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- 2022
34. Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations
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Gerard Temprano‐Sagrera, Colleen M. Sitlani, William P. Bone, Miguel Martin‐Bornez, Benjamin F. Voight, Alanna C. Morrison, Scott M. Damrauer, Paul S. de Vries, Nicholas L. Smith, Maria Sabater‐Lleal, Abbas Dehghan, Adam S Heath, Alanna C Morrison, Alex P Reiner, Andrew Johnson, Anne Richmond, Annette Peters, Astrid van Hylckama Vlieg, Barbara McKnight, Bruce M Psaty, Caroline Hayward, Cavin Ward‐Caviness, Christopher O’Donnell, Daniel Chasman, David P Strachan, David A Tregouet, Dennis Mook‐Kanamori, Dipender Gill, Florian Thibord, Folkert W Asselbergs, Frank W.G. Leebeek, Frits R Rosendaal, Gail Davies, Georg Homuth, Gerard Temprano, Harry Campbell, Herman A Taylor, Jan Bressler, Jennifer E Huffman, Jerome I Rotter, Jie Yao, James F Wilson, Joshua C Bis, Julie M Hahn, Karl C Desch, Kerri L Wiggins, Laura M Raffield, Lawrence F Bielak, Lisa R Yanek, Marcus E Kleber, Martina Mueller, Maryam Kavousi, Massimo Mangino, Melissa Liu, Michael R Brown, Matthew P Conomos, Min‐A Jhun, Ming‐Huei Chen, Moniek P.M. de Maat, Nathan Pankratz, Nicholas L Smith, Patricia A Peyser, Paul Elliot, Paul S de Vries, Peng Wei, Philipp S Wild, Pierre E Morange, Pim van der Harst, Qiong Yang, Ngoc‐Quynh Le, Riccardo Marioni, Ruifang Li, Scott M Damrauer, Simon R Cox, Stella Trompet, Stephan B Felix, Uwe Völker, Weihong Tang, Wolfgang Koenig, J. Wouter Jukema, Xiuqing Guo, Sara Lindstrom, Lu Wang, Erin N Smith, William Gordon, Mariza de Andrade, Jennifer A Brody, Jack W Pattee, Jeffrey Haessler, Ben M Brumpton, Daniel I Chasman, Pierre Suchon, Constance Turman, Marine Germain, James MacDonald, Sigrid K Braekkan, Sebastian M Armasu, Rabecca D Jackson, Jonas B Nielsen, Franco Giulianini, Marja K Puurunen, Manal Ibrahim, Susan R Heckbert, Theo K Bammler, Kelly A Frazer, Bryan M McCauley, Kent Taylor, James S Pankow, Alexander P Reiner, Maiken E Gabrielsen, Jean‐François Deleuze, Chris J O’Donnell, Jihye Kim, Peter Kraft, John‐Bjarne Hansen, John A Heit, Charles Kooperberg, Kristian Hveem, Paul M Ridker, Pierre‐Emmanuel Morange, Andrew D Johnson, Christopher Kabrhel, David‐Alexandre Trégouët, Rainer Malik, Ganesh Chauhan, Matthew Traylor, Muralidharan Sargurupremraj, Yukinori Okada, Aniket Mishra, Loes Rutten‐Jacobs, Anne‐Katrin Giese, Sander W van der Laan, Solveig Gretarsdottir, Christopher D Anderson, Michael Chong, Hieab HH Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, Traci M Bartz, Oscar R Benavente, Steve Bevan, Giorgio B Boncoraglio, Robert D Brown, Adam S Butterworth, Caty Carrera, Cara L Carty, Wei‐Min Chen, John W Cole, Adolfo Correa, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul IW de Bakker, Anita L DeStefano, Marcel den Hoed, Qing Duan, Stefan T Engelter, Guido J Falcone, Rebecca F Gottesman, Raji P Grewal, Vilmundur Gudnason, Stefan Gustafsson, Tamara B Harris, Ahamad Hassan, Aki S Havulinna, Elizabeth G Holliday, George Howard, Fang‐Chi Hsu, Hyacinth I Hyacinth, M Arfan Ikram, Erik Ingelsson, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez‐Conde, Julie A Johnson, J Wouter Jukema, Masahiro Kanai, Keith L Keene, Brett M Kissela, Dawn O Kleindorfer, Michiaki Kubo, Leslie A Lange, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Jin‐Moo Lee, Robin Lemmens, Didier Leys, Cathryn M Lewis, Wei‐Yu Lin, Arne G Lindgren, Erik Lorentzen, Patrik K Magnusson, Jane Maguire, Ani Manichaikul, Patrick F McArdle, James F Meschia, Braxton D Mitchell, Thomas H Mosley, Michael A Nalls, Toshiharu Ninomiya, Martin J O’Donnell, Sara L Pulit, Kristiina Rannikmäe, Kathryn M Rexrode, Kenneth Rice, Stephen S Rich, Natalia S Rost, Peter M Rothwell, Tatjana Rundek, Ralph L Sacco, Saori Sakaue, Michele M Sale, Veikko Salomaa, Bishwa R Sapkota, Reinhold Schmidt, Carsten O Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie LM Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D Taylor, Vincent NS Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Christophe Tzourio, Cornelia M van Duijn, Matthew Walters, Nicholas J Wareham, Sylvia Wassertheil‐Smoller, James G Wilson, Salim Yusuf, Najaf Amin, Hugo S Aparicio, Donna K Arnett, John Attia, Alexa S Beiser, Claudine Berr, Julie E Buring, Mariana Bustamante, Valeria Caso, Yu‐Ching Cheng, Seung Hoan Choi, Ayesha Chowhan, Natalia Cullell, Jean‐François Dartigues, Hossein Delavaran, Pilar Delgado, Marcus Dörr, Gunnar Engström, Ian Ford, Wander S Gurpreet, Anders Hamsten, Laura Heitsch, Atsushi Hozawa, Laura Ibanez, Andreea Ilinca, Martin Ingelsson, Motoki Iwasaki, Rebecca D Jackson, Katarina Jood, Pekka Jousilahti, Sara Kaffashian, Lalit Kalra, Masahiro Kamouchi, Takanari Kitazono, Olafur Kjartansson, Manja Kloss, Peter J Koudstaal, Jerzy Krupinski, Daniel L Labovitz, Cathy C Laurie, Christopher R Levi, Linxin Li, Lars Lind, Cecilia M Lindgren, Vasileios Lioutas, Yong Mei Liu, Oscar L Lopez, Hirata Makoto, Nicolas Martinez‐Majander, Koichi Matsuda, Naoko Minegishi, Joan Montaner, Andrew P Morris, Elena Muiño, Martina Müller‐Nurasyid, Bo Norrving, Soichi Ogishima, Eugenio A Parati, Leema Reddy Peddareddygari, Nancy L Pedersen, Joanna Pera, Markus Perola, Alessandro Pezzini, Silvana Pileggi, Raquel Rabionet, Iolanda Riba‐Llena, Marta Ribasés, Jose R Romero, Jaume Roquer, Anthony G Rudd, Antti‐Pekka Sarin, Ralhan Sarju, Chloe Sarnowski, Makoto Sasaki, Claudia L Satizabal, Mamoru Satoh, Naveed Sattar, Norie Sawada, Gerli Sibolt, Ásgeir Sigurdsson, Albert Smith, Kenji Sobue, Carolina Soriano‐Tárraga, Tara Stanne, O Colin Stine, David J Stott, Konstantin Strauch, Takako Takai, Hideo Tanaka, Kozo Tanno, Alexander Teumer, Liisa Tomppo, Nuria P Torres‐Aguila, Emmanuel Touze, Shoichiro Tsugane, Andre G Uitterlinden, Einar M Valdimarsson, Sven J van der Lee, Henry Völzke, Kenji Wakai, David Weir, Stephen R Williams, Charles DA Wolfe, Quenna Wong, Huichun Xu, Taiki Yamaji, Dharambir K Sanghera, Olle Melander, Christina Jern, Daniel Strbian, Israel Fernandez‐Cadenas, W T Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Jemma C Hopewell, Danish Saleheen, Kari Stefansson, Bradford B Worrall, Steven J Kittner, Sudha Seshadri, Myriam Fornage, Hugh S Markus, Joanna MM Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans, and VU University medical center
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Hemostasis ,genome-wide association study ,genetic pleiotropy ,Hematology ,Polymorphism, Single Nucleotide ,Hemostatics ,blood coagulation ,cardiovascular diseases ,Phenotype ,Cardiovascular Diseases ,Tissue Plasminogen Activator ,hemostasis ,Humans ,Genetic Predisposition to Disease ,Factor XI ,Genome-Wide Association Study - Abstract
Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.
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- 2022
35. Maintenance of Acute Stroke Care Service During the COVID-19 Pandemic Lockdown
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Alessandro Pezzini, Valerian L Altersberger, Bruno Gonçalves, Jan F. Scheitz, Andreas Kastrup, Annika Nordanstig, Alessandro Padovani, Patrik Michel, Christian H. Nolte, Susanne Wegener, Marcel Arnold, Andrea Zini, Christian Hametner, Marialuisa Zedde, Peter A. Ringleb, Paul J. Nederkoorn, Ronen R. Leker, Henrik Gensicke, Georges Ntaios, Guillaume Turc, Lotte J. Stolze, Leon A. Rinkel, Stefania Nannoni, Nicolas Martinez-Majander, Georg Kägi, Leo H. Bonati, Alexandros Rentzos, Stefan T. Engelter, Charlotte Cordonnier, Carlo W. Cereda, Sami Curtze, Mauro Gentile, Hilde Hénon, Philipp Baumgartner, Visnja Padjen, Mirjam Rachel Heldner, Urs Fischer, Panagiotis Papanagiotou, GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Graduate School, Neurology, ACS - Atherosclerosis & ischemic syndromes, and ANS - Neurovascular Disorders
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Male ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Original Contributions ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Cohort Studies ,0302 clinical medicine ,quality of care ,Epidemiology ,Pandemic ,Medicine ,Thrombolytic Therapy ,Registries ,Stroke ,Aged, 80 and over ,Thrombolysis ,Middle Aged ,3. Good health ,reperfusion ,Europe ,Hospitalization ,Treatment Outcome ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Female ,Cardiology and Cardiovascular Medicine ,Cohort study ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Critical Care ,Physical Distancing ,Cardiology ,Time-to-Treatment ,03 medical and health sciences ,Clinical and Population Sciences ,Reperfusion therapy ,Severity of illness ,ischemic stroke ,Humans ,Pandemics ,Aged ,Advanced and Specialized Nursing ,business.industry ,COVID-19 ,medicine.disease ,Emergency medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,intracranial hemorrhage - Abstract
Supplemental Digital Content is available in the text., Background and Purpose: Timely reperfusion is an important goal in treatment of eligible patients with acute ischemic stroke. However, during the coronavirus disease 2019 (COVID-19) pandemic, prehospital and in-hospital emergency procedures faced unprecedented challenges, which might have caused a decline in the number of acute reperfusion therapy applied and led to a worsening of key quality measures for this treatment during lockdown. Methods: This prospective multicenter cohort study used data from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry of patients with acute ischemic stroke treated with reperfusion therapies, that is, intravenous thrombolysis or endovascular therapy. We compared prehospital and in-hospital time-based performance measures (stroke-onset-to-admission, admission-to-treatment, admission-to-image, and image-to-treatment time) during the first 6 weeks after announcement of lockdown (lockdown period) with the same period in 2019 (reference period). Secondary outcomes included stroke severity (National Institutes of Health Stroke Scale) after 24 hours and occurrence of symptomatic intracranial hemorrhage (following the ECASS [European-Australasian Acute Stroke Study]-II criteria). Results: Across 20 stroke centers, 540 patients were treated with intravenous thrombolysis/endovascular therapy during lockdown period compared with 578 patients during reference period (−7% [95% CI, 5%–9%]). Performance measures did not change significantly during the lockdown period (2020/2019 minutes median: onset-to-admission 133/145; admission-to-treatment 51/48). Same was true for admission-to-image (20/19) and image-to-treatment (31/30) time in patients with available time of first image (n=871, 77.9%). Median National Institutes of Health Stroke Scale on admission (2020/2019: 11/11) and after 24 hours (2020/2019: 6/5) and percentage of symptomatic intracranial hemorrhage (2020/2019: 6.2/5.7) did not differ significantly between both periods. Conclusions: The COVID-19 pandemic lockdown resulted in a mild decline in the number of patients with stroke treated with acute reperfusion therapies. More importantly, the solid stability of key quality performance measures between the 2020 and 2019 period may indicate resilience of acute stroke care service during the lockdown, at least in well-established European stroke centers.
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- 2021
36. Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention
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Panagiotis Halvatsiotis, Giuseppe Reale, Jennifer A. Frontera, Giuseppe Martini, S. Pegoraro, Leonardo Pantoni, Aristeidis H. Katsanos, Piergiorgio Lochner, Daniel Strbian, Giorgia Zepponi, Valentina Saia, Karen L. Furie, Giancarlo Agnelli, Elisa Giorli, Erica Scher, Lina Palaiodimou, Valentina Arnao, Giorgio Silvestrelli, Simona Marcheselli, Letizia Riva, Andrea Zini, Angela Risitano, Tiziana Tassinari, Carlo Emanuele Saggese, Francesco Palmerini, Erika Schirinzi, Michael E. Reznik, Marina Mannino, Jukka Putaala, Maria Kosmidou, Michela Giustozzi, Cesare Porta, Maurizio Paciaroni, Marina Padroni, Loris Poli, Maria Cristina Vedovati, Danilo Toni, Manuel Cappellari, Alessandro Rocco, Alessandro Pezzini, Ashkan Shoamanesh, Stefano Forlivesi, Serena Monaco, Raffaele Ornello, Simona Sacco, Silvia Rosa, Shadi Yaghi, Valeria Terruso, Andrea Alberti, Francesco Corea, Elena Ferrari, Christoph Stretz, Marialuisa Zedde, Monica Acciarresi, Cataldo D'Amore, Kateryna Antonenko, Nemanja Popovic, Francesca Guideri, Evangelos Ntais, Boris Doronin, Luca Masotti, Filippo Angelini, Giovanni Orlandi, Licia Denti, Nicola Mumoli, Sotirios Giannopoulos, Elisabetta Toso, Maria Giulia Mosconi, Paolo Aridon, Aurelia Zauli, Giuseppe Micieli, Azmil H. Abdul-Rahim, Laura Brancaleoni, Marina Diomedi, Elisa Grifoni, Georgios Tsivgoulis, Maurizio Acampa, Michele Venti, Walter Ageno, Pietro Caliandro, Alfonso Ciccone, Isabella Canavero, Laura Franco, George Ntaios, Fabio Bandini, Vera Volodina, Pierluigi Bertora, Dimitrios Sagris, Antonio Baldi, Michele Romoli, Hanne Sallinen, Michelangelo Mancuso, Yuriy Flomin, Rossana Tassi, Valeria Caso, Massimo Del Sette, Enrico Maria Lotti, Antonio Gasparro, Alberto Chiti, Jesse Dawson, Brian Mac Grory, Alberto Rigatelli, Paciaroni, Maurizio, Agnelli, Giancarlo, Giustozzi, Michela, Caso, Valeria, Toso, Elisabetta, Angelini, Filippo, Canavero, Isabella, Micieli, Giuseppe, Antonenko, Kateryna, Rocco, Alessandro, Diomedi, Marina, Katsanos, Aristeidis H, Shoamanesh, Ashkan, Giannopoulos, Sotirio, Ageno, Walter, Pegoraro, Samuela, Putaala, Jukka, Strbian, Daniel, Sallinen, Hanne, Mac Grory, Brian C, Furie, Karen L, Stretz, Christoph, Reznik, Michael E, Alberti, Andrea, Venti, Michele, Mosconi, Maria Giulia, Vedovati, Maria Cristina, Franco, Laura, Zepponi, Giorgia, Romoli, Michele, Zini, Andrea, Brancaleoni, Laura, Riva, Letizia, Silvestrelli, Giorgio, Ciccone, Alfonso, Zedde, Maria Luisa, Giorli, Elisa, Kosmidou, Maria, Ntais, Evangelo, Palaiodimou, Lina, Halvatsiotis, Panagioti, Tassinari, Tiziana, Saia, Valentina, Ornello, Raffaele, Sacco, Simona, Bandini, Fabio, Mancuso, Michelangelo, Orlandi, Giovanni, Ferrari, Elena, Pezzini, Alessandro, Poli, Lori, Cappellari, Manuel, Forlivesi, Stefano, Rigatelli, Alberto, Yaghi, Shadi, Scher, Erica, Frontera, Jennifer A, Masotti, Luca, Grifoni, Elisa, Caliandro, Pietro, Zauli, Aurelia, Reale, Giuseppe, Marcheselli, Simona, Gasparro, Antonio, Terruso, Valeria, Arnao, Valentina, Aridon, Paolo, Abdul-Rahim, Azmil H, Dawson, Jesse, Saggese, Carlo Emanuele, Palmerini, Francesco, Doronin, Bori, Volodina, Vera, Toni, Danilo, Risitano, Angela, Schirinzi, Erika, Del Sette, Massimo, Lochner, Piergiorgio, Monaco, Serena, Mannino, Marina, Tassi, Rossana, Guideri, Francesca, Acampa, Maurizio, Martini, Giuseppe, Lotti, Enrico Maria, Padroni, Marina, Pantoni, Leonardo, Rosa, Silvia, Bertora, Pierluigi, Ntaios, George, Sagris, Dimitrio, Baldi, Antonio, D'Amore, Cataldo, Mumoli, Nicola, Porta, Cesare, Denti, Licia, Chiti, Alberto, Corea, Francesco, Acciarresi, Monica, Flomin, Yuriy, Popovic, Nemanja, and Tsivgoulis, Georgios
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Male ,Administration, Oral ,030204 cardiovascular system & hematology ,Settore MED/11 ,0302 clinical medicine ,80 and over ,risk factors ,Medicine ,atrial fibrillation ,Prospective Studies ,Aged, 80 and over ,cerebral hemorrhage ,logistic models ,white matter ,Aged ,Antithrombins ,Atrial Fibrillation ,Case-Control Studies ,Cerebral Hemorrhage ,Female ,Humans ,Middle Aged ,Risk Factors ,Stroke ,Atrial fibrillation ,Vitamin K antagonist ,3. Good health ,Administration ,Settore MED/26 - Neurologia ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Oral ,medicine.medical_specialty ,medicine.drug_class ,Settore MED/26 ,Lower risk ,03 medical and health sciences ,Internal medicine ,cardiovascular diseases ,logistic model ,Advanced and Specialized Nursing ,Intracerebral hemorrhage ,business.industry ,Warfarin ,medicine.disease ,Clinical trial ,Concomitant ,Heart failure ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.
- Published
- 2021
37. Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study
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Maurizio Paciaroni, Valeria Caso, Giancarlo Agnelli, Maria Giulia Mosconi, Michela Giustozzi, David Julian Seiffge, Stefan T. Engelter, Philippe Lyrer, Alexandros A. Polymeris, Lilian Kriemler, Annaelle Zietz, Jukka Putaala, Daniel Strbian, Liisa Tomppo, Patrik Michel, Davide Strambo, Alexander Salerno, Suzette Remillard, Manuela Buehrer, Odessa Bavaud, Peter Vanacker, Susanna Zuurbier, Laetitia Yperzeele, Caroline M.J. Loos, Manuel Cappellari, Andrea Emiliani, Marialuisa Zedde, Azmil Abdul-Rahim, Jesse Dawson, Robert Cronshaw, Erika Schirinzi, Massimo Del Sette, Christoph Stretz, Narendra Kala, Michael Reznik, Ashley Schomer, Brian Mac Grory, Mahesh Jayaraman, Ryan McTaggart, Shadi Yaghi, Karen L. Furie, Luca Masotti, Elisa Grifoni, Danilo Toni, Angela Risitano, Anne Falcou, Luca Petraglia, Enrico Maria Lotti, Marina Padroni, Lucia Pavolucci, Piergiorgio Lochner, Giorgio Silvestrelli, Alfonso Ciccone, Andrea Alberti, Michele Venti, Laura Traballi, Chiara Urbini, Odysseas Kargiotis, Alessandro Rocco, Marina Diomedi, Simona Marcheselli, Pietro Caliandro, Aurelia Zauli, Giuseppe Reale, Kateryna Antonenko, Eugenia Rota, Tiziana Tassinari, Valentina Saia, Francesco Palmerini, Paolo Aridon, Valentina Arnao, Serena Monaco, Salvatore Cottone, Antonio Baldi, Cataldo D’Amore, Walter Ageno, Samuela Pegoraro, George Ntaios, Dimitrios Sagris, Sotirios Giannopoulos, Maria Kosmidou, Evangelos Ntais, Michele Romoli, Leonardo Pantoni, Silvia Rosa, Pierluigi Bertora, Alberto Chiti, Isabella Canavero, Carlo Emanuele Saggese, Maurizio Plocco, Elisa Giorli, Lina Palaiodimou, Eleni Bakola, Georgios Tsivgoulis, Fabio Bandini, Antonio Gasparro, Valeria Terruso, Marina Mannino, Alessandro Pezzini, Raffaele Ornello, Simona Sacco, Nemanja Popovic, Umberto Scoditti, Antonio Genovese, Licia Denti, Yuriy Flomin, Michelangelo Mancuso, Elena Ferrari, Maria Chiara Caselli, Leonardo Ulivi, Nicola Giannini, Gian Marco De Marchis, Paciaroni, Maurizio, Caso, Valeria, Agnelli, Giancarlo, Mosconi, Maria Giulia, Giustozzi, Michela, Seiffge, David Julian, Engelter, Stefan T, Lyrer, Philippe, Polymeris, Alexandros A, Kriemler, Lilian, Zietz, Annaelle, Putaala, Jukka, Strbian, Daniel, Tomppo, Liisa, Michel, Patrik, Strambo, Davide, Salerno, Alexander, Remillard, Suzette, Buehrer, Manuela, Bavaud, Odessa, Vanacker, Peter, Zuurbier, Susanna, Yperzeele, Laetitia, Loos, Caroline M J, Cappellari, Manuel, Emiliani, Andrea, Zedde, Marialuisa, Abdul-Rahim, Azmil, Dawson, Jesse, Cronshaw, Robert, Schirinzi, Erika, Del Sette, Massimo, Stretz, Christoph, Kala, Narendra, Reznik, Michael, Schomer, Ashley, Grory, Brian Mac, Jayaraman, Mahesh, McTaggart, Ryan, Yaghi, Shadi, Furie, Karen L, Masotti, Luca, Grifoni, Elisa, Toni, Danilo, Risitano, Angela, Falcou, Anne, Petraglia, Luca, Lotti, Enrico Maria, Padroni, Marina, Pavolucci, Lucia, Lochner, Piergiorgio, Silvestrelli, Giorgio, Ciccone, Alfonso, Alberti, Andrea, Venti, Michele, Traballi, Laura, Urbini, Chiara, Kargiotis, Odyssea, Rocco, Alessandro, Diomedi, Marina, Marcheselli, Simona, Caliandro, Pietro, Zauli, Aurelia, Reale, Giuseppe, Antonenko, Kateryna, Rota, Eugenia, Tassinari, Tiziana, Saia, Valentina, Palmerini, Francesco, Aridon, Paolo, Arnao, Valentina, Monaco, Serena, Cottone, Salvatore, Baldi, Antonio, D'Amore, Cataldo, Ageno, Walter, Pegoraro, Samuela, Ntaios, George, Sagris, Dimitrio, Giannopoulos, Sotirio, Kosmidou, Maria, Ntais, Evangelo, Romoli, Michele, Pantoni, Leonardo, Rosa, Silvia, Bertora, Pierluigi, Chiti, Alberto, Canavero, Isabella, Saggese, Carlo Emanuele, Plocco, Maurizio, Giorli, Elisa, Palaiodimou, Lina, Bakola, Eleni, Tsivgoulis, Georgio, Bandini, Fabio, Gasparro, Antonio, Terruso, Valeria, Mannino, Marina, Pezzini, Alessandro, Ornello, Raffaele, Sacco, Simona, Popovic, Nemanja, Scoditti, Umberto, Genovese, Antonio, Denti, Licia, Flomin, Yuriy, Mancuso, Michelangelo, Ferrari, Elena, Caselli, Maria Chiara, Ulivi, Leonardo, Giannini, Nicola, De Marchis, Gian Marco, and Neurology
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Oral ,Advanced and Specialized Nursing ,hypertension ,recurrence ,anticoagulant ,Administration, Oral ,Anticoagulants ,Hemorrhage ,Settore MED/26 ,Brain Ischemia ,Stroke ,Risk Factors ,Administration ,Atrial Fibrillation ,Humans ,Settore MED/26 - Neurologia ,Human medicine ,Neurology (clinical) ,Prospective Studies ,Cardiology and Cardiovascular Medicine ,atrial fibrillation ,ischemic stroke ,Ischemic Stroke - Abstract
Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.
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- 2022
38. Lifting the mask on neurological manifestations of COVID-19
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Alessandro Padovani and Alessandro Pezzini
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0301 basic medicine ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Clinical Neurology ,medicine.disease_cause ,Betacoronavirus ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Preclinical research ,0302 clinical medicine ,medicine ,Humans ,In patient ,Intensive care medicine ,Pandemics ,Coronavirus ,SARS-CoV-2 ,business.industry ,COVID-19 ,Research Highlight ,030104 developmental biology ,Perspective ,Neurology (clinical) ,Nervous System Diseases ,Coronavirus Infections ,business ,Neurological disorders ,030217 neurology & neurosurgery - Abstract
As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic spreads, it is becoming increasingly evident that coronavirus disease 2019 (COVID-19) is not limited to the respiratory system, and that other organs can be affected. In particular, virus-related neurological manifestations are being reported more and more frequently in the scientific literature. In this article, we review the literature on the association between COVID-19 and neurological manifestations, present evidence from preclinical research suggesting that SARS-CoV-2 could be responsible for many of these manifestations, and summarize the biological pathways that could underlie each neurological symptom. Understanding the mechanisms that lead to neurological manifestations in patients with COVID-19 and how these manifestations correlate with clinical outcomes will be instrumental in guiding the optimal use of targeted therapeutic strategies., In this Perspective, Pezzini and Padovani critique the evidence for neurological manifestations of COVID-19, including epidemiological, neuropathological and neuroimaging data, and highlight the need for further work to establish whether SARS-CoV-2 is responsible for these symptoms.
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- 2020
39. Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes
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Michele Venti, Walter Ageno, Alfonso Ciccone, Luana Gentile, Vanessa Gourbali, Antonio Baldi, Elisa Grifoni, László Csiba, Cataldo D'Amore, Prasanna Tadi, Yuriy Flomin, Rossana Tassi, Sung Il Sohn, Bruno Bonetti, Patrik Michel, Erika Schirinzi, Alessandro Padovani, Cindy Tiseo, Maria Luisa De Lodovici, Odysseas Kargiotis, Konstantinos Vadikolias, Shadi Yaghi, Maurizio Paciaroni, Georgios Tsivgoulis, Enrico Maria Lotti, Manuel Cappellari, Lilla Szabó, Ashraf Eskandari, Federica Letteri, Leonardo Ulivi, Chrissoula Liantinioti, Valeria Caso, Lina Palaiodimou, Dirk Deleu, Jesse Dawson, Licia Denti, Konstantinos Makaritsis, Gianni Lorenzini, Marina Mannino, Monica Acciarresi, Miriam Maccarrone, Nicola Mumoli, Marta Bellesini, Simona Sacco, George Athanasakis, Umberto Scoditti, Maurizio Acampa, Giuseppe Martini, Brian Mac Grory, Alberto Rigatelli, Kristian Barlinn, Vieri Vannucchi, Serena Monaco, Efstathia Karagkiozi, Elisa Giorli, Francesca Guideri, Martina Giuntini, Dorjan Zabzuni, Davide Imberti, Giorgio Silvestrelli, Luca Masotti, Loris Poli, Karen L. Furie, Alessio Pieroni, Marialuisa Zedde, Franco Galati, Andrea Alberti, Giancarlo Agnelli, Jessica Barlinn, Turgut Tatlisumak, Maria Chiara Caselli, Boris Doronin, Liisa Tomppo, Kennedy R. Lees, Mario Maimone Baronello, Maria Giulia Mosconi, Jukka Putaala, Tiziana Tassinari, Azmil H. Abdul-Rahim, Peter Vanacker, Christina Rueckert, Valentina Bogini, Alessandro Pezzini, Francesco Corea, Giovanni Orlandi, Simona Marcheselli, Michela Giustozzi, Theodore Karapanayiotides, Michelangelo Mancuso, George Ntaios, Fabio Bandini, Vera Volodina, Nicola Giannini, Cesare Porta, Danilo Toni, Alberto Chiti, and Massimo Del Sette
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Severe bleeding ,medicine.medical_specialty ,Stroke recurrence ,Infarction ,stroke recurrence ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Original Research Articles ,Internal medicine ,Ischaemic stroke ,Acute stroke ,Medicine ,atrial fibrillation ,In patient ,Acute ischemic stroke ,business.industry ,Atrial fibrillation ,medicine.disease ,Cardiology ,Human medicine ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
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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- 2020
40. Association of prestroke metformin use, stroke severity, and thrombolysis outcome
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Sixtine Gilliot, Hebun Erdur, Christian H. Nolte, Paul J. Nederkoorn, Mauro Magoni, Christian Hametner, Andrea Zini, Patrik Michel, Pierre Seners, Michael J Scherrer, Laura P. Westphal, Ashraf Eskandari, Jonathan M. Coutinho, Sami Curtze, Yannick Béjot, Nicolas Martinez-Majander, Céline Brenière, Georg Kägi, Adrien E. Groot, Didier Leys, Alexandros A Polymeris, Laura Vandelli, Ulrike Held, Alessandro Pezzini, Stefan T. Engelter, Andreas R. Luft, Jan F. Scheitz, Marcel Arnold, Marjaana Tiainen, Roni Widmer, Klaus Steigmiller, Susanne Wegener, Peter A. Ringleb, Christopher Traenka, Mirjam Rachel Heldner, Visnja Padjen, Dejana R. Jovanović, Turgut Tatlisumak, Guillaume Turc, Henrik Gensicke, University of Zurich, Neurology, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, Graduate School, and ACS - Amsterdam Cardiovascular Sciences
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,610 Medicine & health ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Fibrinolytic Agents ,Modified Rankin Scale ,Internal medicine ,Diabetes mellitus ,Epidemiology ,medicine ,Humans ,Hypoglycemic Agents ,Thrombolytic Therapy ,cardiovascular diseases ,10064 Neuroscience Center Zurich ,Stroke ,Aged ,Retrospective Studies ,business.industry ,Recovery of Function ,10060 Epidemiology, Biostatistics and Prevention Institute (EBPI) ,Thrombolysis ,Middle Aged ,medicine.disease ,Metformin ,10040 Clinic for Neurology ,3. Good health ,2728 Neurology (clinical) ,Diabetes Mellitus, Type 2 ,Propensity score matching ,Cohort ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
ObjectiveTo evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after IV thrombolysis (IVT), we analyzed a cohort of 1,919 patients with stroke with type 2 diabetes mellitus in a multicenter exploratory analysis.MethodsData from patients with diabetes and ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET.ResultsOf 1,919 patients with stroke with type 2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1,162 (61%) had not (MET−). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets, or antihypertensives were more common in the MET+ group. After PSM, the 2 groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIH Stroke Scale 10.0 ± 6.7 vs 11.3 ± 6.5), 3-month degree of independence on modified Rankin Scale (2 [interquartile range (IQR) 1.0–4.0] vs 3 [IQR 1.0–4.0]), as well as mortality (12.5% vs 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well-balanced between the groups.ConclusionsPatients with stroke and diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.
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- 2020
41. Effect of haemoglobin levels on outcome in intravenous thrombolysis-treated stroke patients
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Stefan T. Engelter, Sophie A. van den Berg, Gerli Sibolt, Alessandro Pezzini, Simon Jung, Marjaana Tiainen, Stefania Nannoni, Nicolas Martinez-Majander, Georg Kägi, Abdulaziz S Al Sultan, Lars Kellert, Sami Curtze, Thomas P. Zonneveld, Visnja Padjen, Paul J. Nederkoorn, Andrea Zini, Henrik Gensicke, Christian Hametner, Ashraf Eskandari, Gian M DeMarchis, Philippe Lyrer, Leo H. Bonati, Peter A. Ringleb, Silja Räty, Stefania Maffei, Valerian L Altersberger, Patrik Michel, Mirjam Rachel Heldner, Alexandros A Polymeris, Marcel Arnold, HUS Neurocenter, Neurologian yksikkö, University of Helsinki, Helsinki University Hospital Area, Department of Neurosciences, Graduate School, ACS - Atherosclerosis & ischemic syndromes, Amsterdam Neuroscience - Neurovascular Disorders, and Neurology
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EXPRESSION ,BLOOD-TRANSFUSION ,Blood transfusion ,Stroke patient ,Anemia ,Iv thrombolysis ,CELL TRANSFUSION ,IMPACT ,medicine.medical_treatment ,Haemoglobin levels ,Anaemia ,030204 cardiovascular system & hematology ,GUIDELINES ,3124 Neurology and psychiatry ,03 medical and health sciences ,0302 clinical medicine ,Original Research Articles ,medicine ,In patient ,intravenous thrombolysis ,ANEMIA ,Stroke ,RISK ,business.industry ,3112 Neurosciences ,Thrombolysis ,medicine.disease ,haemoglobin ,stroke ,3. Good health ,IV THROMBOLYSIS ,polyglobulia ,Anesthesia ,TRANSFUSION THRESHOLDS ,outcome ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
Introduction Alterations in haemoglobin levels are frequent in stroke patients. The prognostic meaning of anaemia and polyglobulia on outcomes in patients treated with intravenous thrombolysis is ambiguous. Patients and methods In this prospective multicentre, intravenous thrombolysis register-based study, we compared haemoglobin levels on hospital admission with three-month poor outcome (modified Rankin Scale 3–6), mortality and symptomatic intracranial haemorrhage (European Cooperative Acute Stroke Study II-criteria (ECASS-II-criteria)). Haemoglobin level was used as continuous and categorical variable distinguishing anaemia (female: 15.5 g/dl; male: >17 g/dl). Anaemia was subdivided into mild and moderate/severe (female/male: Results Among 6866 intravenous thrombolysis-treated stroke patients, 5448 (79.3%) had normal haemoglobin level, 1232 (17.9%) anaemia – of those 903 (13.2%) had mild and 329 (4.8%) moderate/severe anaemia – and 186 (2.7%) polyglobulia. Anaemia was associated with poor outcome (ORadjusted 1.25 (1.05–1.48)) and mortality (ORadjusted 1.58 (1.27–1.95)). In anaemia subgroups, both mild and moderate/severe anaemia independently predicted poor outcome (ORadjusted 1.29 (1.07–1.55) and 1.48 (1.09–2.02)) and mortality (ORadjusted 1.45 (1.15–1.84) and ORadjusted 2.00 (1.46–2.75)). Each haemoglobin level decrease by 1 g/dl independently increased the risk of poor outcome (ORadjusted 1.07 (1.02–1.11)) and mortality (ORadjusted 1.08 (1.02–1.15)). Anaemia was not associated with occurrence of symptomatic intracranial haemorrhage. Polyglobulia did not change any outcome. Discussion The more severe the anaemia, the higher the probability of poor outcome and death. Severe anaemia might be a target for interventions in hyperacute stroke. Conclusion Anaemia on admission, but not polyglobulia, is a strong and independent predictor of poor outcome and mortality in intravenous thrombolysis-treated stroke patients.
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- 2020
42. Long-term outcome of cervical artery dissection
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Carlo Gandolfo, Maurizia Rasura, Alessandro Padovani, Maurizio Paciaroni, Marina Mannino, Sandro Sanguigni, Maurizio Melis, Maria Sessa, Giorgio Silvestrelli, Massimo Del Sette, Sonia Bonacina, Mauro Magoni, Paolo Cerrato, Alessandro Adami, Andrea Morotti, Maria Vittoria Calloni, Alessandro Pezzini, Carla Zanferrari, Patrizia Nencini, Giuseppe Micieli, Manuel Cappellari, Mario Grassi, Martina Locatelli, Marialuisa Zedde, Giuseppina Calabrese, Valeria Bignamini, Claudio Baracchini, Simona Marcheselli, Valeria Terruso, Anna Bersano, Paolo La Spina, Rita Bella, Eugenio Magni, Elisa Giorli, Corrado Lodigiani, Andrea Zini, Rocco Salvatore Calabrò, Enrico Maria Lotti, Fabio Melis, Anna Cavallini, Cristiano Azzini, Maria Luisa DeLodovici, Carlo Dallocchio, Rossana Tassi, Massimiliano Braga, and Mauro Gentile
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Pediatrics ,medicine.medical_specialty ,Longitudinal study ,Subarachnoid hemorrhage ,Cervical Artery ,Dermatology ,Cervical artery dissection ,arteries ,03 medical and health sciences ,Stroke in young adults ,0302 clinical medicine ,cohort studies ,multicenter studies as topic ,risk factors ,Medicine ,030212 general & internal medicine ,cervical artery dissection ,outcome ,stroke in young adults ,adolescent ,dissection ,female ,humans ,Italy ,stroke ,vertebral artery dissection ,Risk factor ,Stroke ,Outcome ,Neuroradiology ,business.industry ,General Medicine ,medicine.disease ,Psychiatry and Mental health ,Dissection ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
Long-term consequences of cervical artery dissection (CeAD), a major cause of ischemic stroke in young people, have been poorly investigated. The Italian Project on Stroke at Young Age - Cervical Artery Dissection (IPSYS CeAD) project is a multicenter, hospital-based, consecutively recruiting, observational, cohort study aimed to address clinically important questions about long-term outcome of CeAD patients, which are not covered by other large-scale registries. Patients with radiologically diagnosed CeAD were consecutively included in the registry. Baseline demographic and clinical variables, as well as information on risk factors, were systematically collected for each eligible patient. Follow-up evaluations were conducted between 3 and 6 months after the initial event (t1) and then annually (t2 at 1 year, t3 at 2 years , and so on), in order to assess outcome events (long-term recurrent CeAD, any fatal/nonfatal ischemic stroke, transient ischemic attack (TIA), or other arterial thrombotic event, and death from any cause). Between 2000 and 2019, data from 1530 patients (age at diagnosis, 47.2 ± 11.5 years; women, 660 [43.1%]) have been collected at 39 Italian neurological centers. Dissection involved a single vessel in 1308 (85.5%) cases and caused brain ischemia in 1303 (85.1%) (190 TIA/1113 ischemic stroke). Longitudinal data are available for 1414 (92.4%) patients (median follow-up time in patients who did not experience recurrent events, 36.0 months [25th to 75th percentile, 63.0]). The collaborative IPSYS CeAD effort will provide novel information on the long-term outcome of CeAD patients. This could allow for tailored treatment approaches based on patients' individual characteristics.
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- 2020
43. Subarachnoid Extension Predicts Lobar Intracerebral Hemorrhage Expansion
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Mauro Magoni, Loris Poli, Massimo Gamba, Giorgio Busto, Paolo Costa, Federico Mazzacane, Valeria De Giuli, Eleonora Leuci, Enrico Fainardi, Elisa Candeloro, Anna Cavallini, Giuseppe Micieli, Ilaria Casetta, Alessandro Padovani, Andrea Morotti, and Alessandro Pezzini
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Male ,medicine.medical_specialty ,Logistic regression ,NO ,Cohort Studies ,hematoma expansion ,Internal medicine ,subarachnoid extension ,medicine ,Humans ,computed tomography ,intracerebral hemorrhage ,stroke ,Stroke ,Aged ,Cerebral Hemorrhage ,Retrospective Studies ,Advanced and Specialized Nursing ,Intracerebral hemorrhage ,Hematoma ,Univariate analysis ,business.industry ,Confounding ,Brain ,Reproducibility of Results ,Odds ratio ,Middle Aged ,medicine.disease ,Logistic Models ,Cohort ,Population study ,Female ,Neurology (clinical) ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background and Purpose— We investigated whether subarachnoid extension (SAHE) of intracerebral hemorrhage (ICH) is associated with hematoma expansion (HE). Methods— Retrospective analysis of patients with primary spontaneous ICH admitted at 3 academic hospitals in Italy. The study population was divided into a development and a replication cohort. SAHE was rated on baseline noncontrast computed tomography by investigators blinded to clinical data. The main outcome of interest was HE, defined as ICH growth >33% mL and/or >6 mL. Predictors of HE were explored with multivariable logistic regression stratified by ICH location (lobar versus nonlobar). Results— A total of 360 and 192 patients were included in the development and replication cohort, respectively. SAHE was identified with good interrater reliability ( K =0.82), and its frequency was 27.8% in the development and 24.5% in the replication cohort. In univariate analysis, HE was more common in patients with SAHE (52.0% versus 27.3%; P P =0.001) whereas there was no association with HE in nonlobar ICH (odds ratio, 0.55 [95% CI, 0.17–1.84]; P =0.334). The increased risk of HE in lobar ICH with SAHE was confirmed in the replication cohort (odds ratio, 3.46 [95% CI, 1.07–11.20]; P =0.038). Conclusions— SAHE predicts HE in lobar ICH. This may improve the stratification of HE risk in clinical practice or future trials targeting HE. Further research is needed to confirm our findings and characterize the underlying biological mechanisms.
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- 2020
44. Imaging markers of intracerebral hemorrhage expansion in patients with unclear symptom onset
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Andrea Morotti, Gregoire Boulouis, Andreas Charidimou, Loris Poli, Paolo Costa, Valeria De Giuli, Eleonora Leuci, Federico Mazzacane, Giorgio Busto, Francesco Arba, Laura Brancaleoni, Sebastiano Giacomozzi, Luigi Simonetti, Michele Laudisi, Anna Cavallini, Massimo Gamba, Mauro Magoni, Claudio Cornali, Marco M Fontanella, Andrew D Warren, Edip M Gurol, Anand Viswanathan, Roberto Gasparotti, Ilaria Casetta, Enrico Fainardi, Andrea Zini, Alessandro Pezzini, Alessandro Padovani, Steven M Greenberg, Jonathan Rosand, and Joshua N Goldstein
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Male ,Hematoma ,Anticoagulants ,unclear onset ,intracerebral hemorrhage ,Stroke ,Economica ,Neurology ,hematoma expansion ,outcome ,Humans ,Female ,CT ,Prospective Studies ,Biomarkers ,Retrospective Studies ,Cerebral Hemorrhage - Abstract
Background: Hematoma expansion (HE) is common and associated with poor outcome in intracerebral hemorrhage (ICH) with unclear symptom onset (USO). Aims: We tested the association between non-contrast computed tomography (NCCT) markers and HE in this population. Methods: Retrospective analysis of patients with primary spontaneous ICH admitted at five centers in the United States and Italy. Baseline NCCT was analyzed for presence of the following markers: intrahematoma hypodensities, heterogeneous density, blend sign, and irregular shape. Variables associated with HE (hematoma growth > 6 mL and/or > 33% from baseline to follow-up imaging) were explored with multivariable logistic regression. Results: Of 2074 patients screened, we included 646 subjects (median age = 75, 53.9% males), of whom 178 (27.6%) had HE. Hypodensities (odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.79–3.98), heterogeneous density (OR = 2.16, 95% CI = 1.46–3.21), blend sign (OR = 2.28, 95% CI = 1.38–3.75) and irregular shape (OR = 1.82, 95% CI = 1.21–2.75) were independently associated with a higher risk of HE, after adjustment for confounders (ICH volume, anticoagulation, and time from last seen well (LSW) to NCCT). Hypodensities had the highest sensitivity for HE (0.69), whereas blend sign was the most specific marker (0.90). All NCCT markers were more frequent in early presenters (time from LSW to NCCT ⩽ 6 h, n = 189, 29.3%), and more sensitive in this population as well (hypodensities had 0.77 sensitivity). Conclusion: NCCT markers are associated with HE in ICH with USO. These findings require prospective replication and suggest that NCCT features may help the stratification of HE in future studies on USO patients.
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- 2022
45. Antithrombotic therapy in the postacute phase of cervical artery dissection: the Italian Project on Stroke in Young Adults Cervical Artery Dissection
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Debora Pezzini, Mario Grassi, Maria Luisa Zedde, Andrea Zini, Anna Bersano, Carlo Gandolfo, Giorgio Silvestrelli, Claudio Baracchini, Paolo Cerrato, Corrado Lodigiani, Simona Marcheselli, Maurizio Paciaroni, Maurizia Rasura, Manuel Cappellari, Massimo Del Sette, Anna Cavallini, Andrea Morotti, Giuseppe Micieli, Enrico Maria Lotti, Maria Luisa Delodovici, Mauro Gentile, Mauro Magoni, Cristiano Azzini, Maria Vittoria Calloni, Elisa Giorli, Massimiliano Braga, Paolo La Spina, Fabio Melis, Rossana Tassi, Valeria Terruso, Rocco Salvatore Calabrò, Valeria Piras, Alessia Giossi, Martina Locatelli, Valentina Mazzoleni, Sandro Sanguigni, Carla Zanferrari, Marina Mannino, Irene Colombo, Carlo Dallocchio, Patrizia Nencini, Valeria Bignamini, Alessandro Adami, Paolo Costa, Rita Bella, Rosario Pascarella, Alessandro Padovan, and Alessandro Pezzini
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Vertebral Artery Dissection ,Young Adult ,Psychiatry and Mental health ,Fibrinolytic Agents ,Humans ,Surgery ,CEREBROVASCULAR DISEASE ,Arteries ,Neurology (clinical) ,CLINICAL NEUROLOGY ,STROKE ,Brain Ischemia - Abstract
ObjectiveTo explore the impact of antithrombotic therapy discontinuation in the postacute phase of cervical artery dissection (CeAD) on the mid-term outcome of these patients.MethodsIn a cohort of consecutive patients with first-ever CeAD, enrolled in the setting of the multicentre Italian Project on Stroke in Young Adults Cervical Artery Dissection, we compared postacute (beyond 6 months since the index CeAD) outcomes between patients who discontinued antithrombotic therapy and patients who continued taking antithrombotic agents during follow-up. Primary outcome was a composite of ischaemic stroke and transient ischaemic attack. Secondary outcomes were (1) Brain ischaemia ipsilateral to the dissected vessel and (2) Recurrent CeAD. Associations with the outcome of interest were assessed by the propensity score (PS) method.ResultsOf the 1390 patients whose data were available for the outcome analysis (median follow-up time in patients who did not experience outcome events, 36.0 months (25th–75th percentile, 62.0)), 201 (14.4%) discontinued antithrombotic treatment. Primary outcome occurred in 48 patients in the postacute phase of CeAD. In PS-matched samples (201 vs 201), the incidence of primary outcomes among patients taking antithrombotics was comparable with that among patients who discontinued antithrombotics during follow-up (5.0% vs 4.5%; p(log rank test)=0.526), and so was the incidence of the secondary outcomes ipsilateral brain ischaemia (4.5% vs 2.5%; p(log rank test)=0.132) and recurrent CeAD (1.0% vs 1.5%; p(log rank test)=0.798).ConclusionsDiscontinuation of antithrombotic therapy in the postacute phase of CeAD does not appear to increase the risk of brain ischaemia during follow-up.
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- 2022
46. Imaging features and ultraearly hematoma growth in intracerebral hemorrhage associated with COVID-19
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Andrea Morotti, Andrea Pilotto, Valentina Mazzoleni, Enrico Fainardi, Ilaria Casetta, Anna Cavallini, Giulia Del Moro, Elisa Candeloro, Francesco Janes, Paolo Costa, Andrea Zini, Eleonora Leuci, Federico Mazzacane, Serena Magno, Oriela Rustemi, Fabio Raneri, Giuseppe Canova, Mariarosaria Valente, Andrea Giorgianni, Francesca Solazzo, Maurizio Versino, Marco Mauri, Mauro Gentile, Ludovica Migliaccio, Stefano Forlivesi, Eugenio Magni, Elisabetta Del Zotto, Alberto Benussi, Enrico Premi, Massimo Gamba, Loris Poli, Alessandro Pezzini, Roberto Gasparotti, Mauro Magoni, Stefano Gipponi, and Alessandro Padovani
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Hematoma ,SARS-CoV-2 ,Anticoagulants ,COVID-19 ,COVID-19, Intracerebral hemorrhage, SARS-CoV-2, Stroke ,Stroke ,Economica ,Humans ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,cardiovascular diseases ,Intracerebral hemorrhage ,Cardiology and Cardiovascular Medicine ,Biomarkers ,Diagnostic Neuroradiology ,Cerebral Hemorrhage ,Retrospective Studies - Abstract
Purpose Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. Methods Multicenter, retrospective, case–control analysis comparing ICH in COVID-19 patients (COV19 +) versus controls without COVID-19 (COV19 −). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. Results A total of 33 COV19 + patients and 321 COV19 − controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19 + population. uHG was significantly higher among COV19 + patients (median 6.2 mL/h vs 3.1 mL/h, p = 0.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE) = 0.31 (0.11), p = 0.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE) = 0.29 (0.13), p = 0.026). Conclusions ICH in COV19 + patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms.
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- 2022
47. Abstract 9674: Stroke, Migraine, and Cervical Arterial Dissection: Shared Genetics Reveals Concordant and Opposing Risk Mechanisms
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Daniel Chasman, Iyas Daghlas, Muralidharan Sargurupremraj, Rebecca Danning, Padhraig Gormley, Rainer Malik, Philipe Amouyel, Tiina Metso, alessandro pezzini, Tobias Kurth, and Stephanie Debette
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Migraine, stroke, and cervical artery dissection (CeAD) represent a triad of cerebrovascular disorders with pairwise comorbid relationships and vascular involvement. Systematic exploration of their shared genetics may inform shared and divergent etiology. Methods: The largest available GWASs for all three disorders were used, including for subtypes of stroke (ischemic stroke [IS], large artery stroke [LAS], small vessel stroke [SVS], cardioembolic stroke [CE]) and migraine (with aura [MA] and without aura [MO]). For each pair of disorders, genetic correlation was assessed both on a genome-wide basis and within candidate loci for each disorder. Cross-trait meta-analysis was used to identify shared novel candidate loci. Causality of migraine susceptibility on stroke and CeAD was evaluated by Mendelian randomization (MR). Results: Among all pairs of disorders, genome-wide genetic correlation was only observed for CeAD and migraine, particularly MO. Local genetic correlations were more extensive between migraine and CeAD than migraine and stroke or CeAD and stroke, identifying novel CeAD associations at rs6693567 ( ADAMTSL4/ECM1 ), rs11187838 ( PLCE1 ), and rs7940646 ( MRVI1 ), while strengthening prior subthreshold evidence at rs9486725 ( FHL5 ) and rs650724 ( LRP1 ). At known migraine loci, novel associations with stroke had concordant risk alleles for SVS at rs191602009 ( CARF ), and for CE at rs55884259 ( NKX2-5 ). However, at other migraine loci, there were novel associations with opposite risk alleles for all stroke, IS, and SVS at rs55928386 ( HTRA1 ), for LAS at rs11172113 ( LRP1 ), and for all stroke and IS, respectively, at rs1535791 and rs4942561 (both LRCH1 ). rs182923402 (near PTCH1 ) was a novel locus for both migraine and CE with concordant effects. MR supported causal influence of migraine on CeAD (OR [95%CI] per doubling migraine prevalence=1.69 [1.24-2.3], p=0.0009) with concordant risk, but with opposite risk on LAS (0.86 [0.76 - 0.96], p=0.0067). Conclusions: Genetic effects between migraine and CeAD had concordant effects on risk, highlighting vascular functions in migraine and novel CeAD loci. Most shared loci for migraine and stroke subtypes had opposite effects on risk. The LRP1 locus was common to all three disorders.
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- 2021
48. Encephalomyelitis in COVID-19
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Alessandro Padovani, Andrea Pilotto, Alessandro Pezzini, and Alberto Benussi
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- 2021
49. Neurology of COVID-19
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Daniele Velardo, Sara Meoni, Valeria Isella, Nicolaja Girone, Delfina Tosi, Alessandro Innocenti, Orsola Gambini, Francesca Bai, Maria Paola Canevini, Chiara Manfredi, Roberta Ferrucci, Tommaso Bocci, Gaetano Bulfamante, Carlo Ferrarese, Paola Alberti, Beatrice Benatti, Laura Campiglio, Alessandro Padovani, Alessandro Pezzini, Gemma Tumminelli, Alberto Benussi, Elio Clemente Agostoni, Veronica Nisticò, Giulia Michela Pellegrino, Maria Donata Benedetti, Vincenzo Silani, Giacomo P. Comi, Simone Beretta, Gianluca Costamagna, Laura Bertolasi, Valentina Chiesa, Andrea Pilotto, Chiara Vannicola, Giuseppe Francesco Sferrazza Papa, Luca Valvassori, Fabrizio Luiso, Michelangelo Dini, Valentina Toto, Carla Uggetti, Alberto Priori, Elena Moro, Davide Chiumello, Stefano Centanni, Giulia Marchetti, Francesca Lanzani, Benedetta Demartini, Emma Scelzo, Matteo Bonifazi, Laura Carpenito, Laura Brighina, Ilaria Viganò, Marco Scarabello, Roberta Rovito, Antonella d'Arminio Monforte, Angelo Cascio Rizzo, Elisabetta De Bernardi, Giuditta Giussani, and Bernardo Dell'Osso
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medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Direct response ,medicine ,Psychiatry ,Cognitive impairment ,European region ,business ,Subject matter - Abstract
The authors will present a comprehensive account of the neurological aspects of SARS-CoV-2 infection. The aim is to provide a practical clinical book which will serve as a guide for clinicians from all specialties involved in the management of COVID-19 patients. The authors share the extensive clinical experience gained in major hospitals in Lombardy, the first European region to face the COVID-19 emergency in 2020. All are recognized international experts in their respective fields and have been involved in the management of COVID-19 cases from the very beginning of the Italian SARS-CoV-2 outbreak. The text begins with a description of pathobiological and pathophysiological aspects related to the involvement of the nervous system, moving on to the discussion of the neurological complications observed in COVID-19 patients; these range from central to peripheral symptoms, and can occur in the acute or post-acute phases of the disease. Further topics are: neuropathology, seizures and EEG, neuroimaging, delirium, encephalomyelitis, stroke, psychopathology and psychiatry, neuropsychology and cognitive impairment, neuromuscu-lar disorders, and the impact of COVID-19 on other pre-existing neurological disorders. In addi-tion, the book will discuss the new developments in teleneurology approaches, which have been a direct response to the ongoing pandemic. Finally, the possible neurological complications of the COVID-19 vaccines and the neurological complications in children will be considered.Each chapter will present a critical review of the existing literature concerning the specific subject matter, followed by practical clinical recommendations, as well as personal considerations based on the experience gained by each author during the course of the COVID-19 pandemic.Neurology of COVID-19 will be an original and innovative reference book for clinicians of all the specialties involved in the management of patients with SARS-CoV-2 infection. ________________________________________________ List of chapters ________________________________________________
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- 2021
50. Genome-wide association study identifies first locus associated with susceptibility to cerebral venous thrombosis
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Serena M. Passamonti, Aleksander Tkach, José M. Ferro, Susanna M. Zuurbier, Stéphanie Debette, Pankaj Sharma, Christina Jern, Ida Martinelli, Elena Haapaniemi, Patrícia Canhão, Braxton D. Mitchell, Giovanni Favuzzi, Guillaume Paré, Alessandro Pezzini, Antonio Arauz, Erik Lindgren, Donatella Colaizzo, Aude Bagan Triquenot, Véronique Le Cam Duchez, K. Spengos, Marina Colombi, Jonathan M. Coutinho, Rosa Santacroce, Paolo Bucciarelli, B. B. Worrall, Ioana Cotlarciuc, Jukka Putaala, Paolo Costa, Reina Ditta, Maurizio Margaglione, Emanuela Pappalardo, Tiina M. Metso, Jennifer J. Majersik, Steven J. Kittner, Turgut Tatlisumak, Sini Hiltunen, Michelangelo Mancuso, Elvira Grandone, Amanda Hodge, Robin Lemmens, Katarina Jood, Marialuisa Zedde, Matthijs C. Brouwer, Sofia Leal Rodrigues, Gie Ken-Dror, Thomas Marjot, Ynte M. Ruigrok, Maria Abbattista, Diana Aguiar de Sousa, Vincent Thijs, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), HUS Neurocenter, Department of Neurosciences, University of Helsinki, Neurologian yksikkö, Neurology, ANS - Neuroinfection & -inflammation, ACS - Atherosclerosis & ischemic syndromes, and ANS - Neurovascular Disorders
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Adult ,Male ,Oncology ,Linkage disequilibrium ,medicine.medical_specialty ,LINKAGE DISEQUILIBRIUM ,LD ,Single-nucleotide polymorphism ,Genome-wide association study ,DISEASE ,3124 Neurology and psychiatry ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,ABO blood group system ,Internal medicine ,Genetic predisposition ,medicine ,Humans ,Thrombophilia ,Genetic Predisposition to Disease ,Allele ,030304 developmental biology ,Venous Thrombosis ,0303 health sciences ,business.industry ,3112 Neurosciences ,Odds ratio ,Middle Aged ,3. Good health ,Neurology ,Chromosomal region ,RISK-FACTORS ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Neurology (clinical) ,Intracranial Thrombosis ,business ,STROKE ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Objective Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. Methods A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. Results In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 x 10(-24); odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 x 10(-16)). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 x 10(-16)) increased risk of CVT compared with individuals with blood group O. Interpretation We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021
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- 2021
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