Publications by authors named "Alessandro Adami"

36 Publications

Detection of subclinical atrial fibrillation after cryptogenic stroke using implantable cardiac monitors.

Eur J Intern Med 2021 Jul 8. Epub 2021 Jul 8.

"Luigi Sacco" Department of Biomedical and Clinical Sciences, University of Milan, Milano, Italy. Electronic address:

Background: Implantable cardiac monitor (ICM) revealed subclinical atrial fibrillation (SCAF) in up to 30% of cryptogenic stroke (CS) patients in randomized trials. However, real world data are limited.

Objectives: We investigated SCAF occurrence, treatments, clinical outcomes and predictors of SCAF in a multicenter real-world population subjected to ICM after CS.

Methods: From September 2016 to November 2019, 20 Italian centers collected data of consecutive patients receiving ICM after CS and followed with remote and outpatient follow-up according to clinical practice. All device-detected AF events were confirmed by the cardiologist to diagnose SCAF.

Results: ICM was implanted in 334 CS patients (mean age±SD 67.4±11.5 years, 129 (38.6%) females, 242 (76.1%) with CHADS-VASC score≥4). During a follow-up of 23.6 (IQR 14.6-31.5) months, SCAF was diagnosed in 92 (27.5%) patients. First episode was asymptomatic in 81 (88.1%). SCAF daily burden ≥5 minutes was 22.0%, 24.1% and 31.5% at 6, 12, and 24 months after ICM implantation. Median time to first day with AF was 60 (IQR 18-140) days. Female gender, age>69 years, PR interval>160 ms and cortical-subcortical infarct type at enrolment were independently associated with an increased risk of SCAF.

Conclusions: In a real-world population, ICM detected SCAF in more than a quarter of CS patients. This experience confirms the relevance of implanting CS patients, for maximizing the possibilities to detect AF, following failure of Holter monitoring, according to guidelines. However, there is need to demonstrate that shift to oral anticoagulation following SCAF detection is associated with reduced risk of recurrent stroke.
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http://dx.doi.org/10.1016/j.ejim.2021.06.022DOI Listing
July 2021

Poor performance of screening questionnaires for obstructive sleep apnea in male commercial drivers.

Sleep Breath 2021 Jun 16. Epub 2021 Jun 16.

Department of Neurology, Sleep Center, IRCCS Sacro Cuore Don Calabria, via Sempreboni 6, 37024, Negrar, Verona, Italy.

Purpose: Screening commercial drivers (CDs) for obstructive sleep apnea (OSA) reduces the risk of motor vehicle accidents. We evaluated the accuracy of standard OSA questionnaires in a cohort of CDs.

Study Design And Methods: We enrolled consecutive male CDs at 10 discrete transportation companies during their yearly scheduled occupational health visit. The CDs had their anthropometric measures taken; completed the Berlin, STOP, STOP-BANG, OSAS-TTI, SACS, EUROSAS, and ARES questionnaires; and underwent a home sleep apnea test (HSAT) for the determination of their respiratory events index (REI). We assessed the questionnaires' ability to predict OSA (REI ≥ 5 events/h) and moderate-to-severe OSA (REI ≥ 15 events/h).

Results: Among 315 CDs recruited, 243 (77%) completed the study protocol, while 72 subjects were excluded for inadequate HSAT quality. The demographics and clinical data were comparable in both the included and excluded subjects. The included CDs had a median age of 50 years (interquartile range (IQR) 25-70) and a mean body mass index of 27 ± 4 kg/m. One hundred and seventy-one subjects (71%) had OSA, and 68 (28%) had moderate-to-severe OSA. A receiver operating characteristic curve of the questionnaires were 0.51-0.71 for predicting OSA and 0.51-0.66 for moderate-to-severe OSA. The STOP-BANG questionnaire had an unsatisfactory positive predictive value, while all of the other questionnaires had an inadequate negative predictive value.

Conclusions: Standard OSA questionnaires are not suited for screening among CDs. The use of the HSAT could provide an objective evaluation of for OSA in this special population.
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http://dx.doi.org/10.1007/s11325-021-02414-zDOI Listing
June 2021

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Neurology 2021 06 25;96(23):e2824-e2838. Epub 2021 Mar 25.

Department of Neurology (R.G.N., M.H.M., M.Frankel, D.C.H.), Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine, Atlanta; Department of Radiology (M.M.Q., M.A., T.N.N., A.K.) and Radiation Oncology (M.M.Q.), Boston Medical Center, Boston University School of Medicine, Massachusetts; Department of Neurology (S.O.M.), Federal University of Rio Grande do Sul, Porto Alegre; Hospital de Clínicas de Porto Alegre (S.O.M.), Brazil; Department of Stroke Neurology (H. Yamagami), National Hospital Organization, Osaka National Hospital, Japan; Department of Neurology (Z.Q.), Xinqiao Hospital of the Army Medical University, Chongqing, China; Department of Neurology (O.Y.M.), Stroke and Neurointervention Division, Alexandria University Hospital, Alexandria University, Egypt; Boston University School of Medicine (A.S.), Massachusetts; 2nd Department of Neurology (A.C.), Institute of Psychiatry and Neurology, Warsaw, Poland; Department of Neurology (G.T., L.P.), National & Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece; Faculdade de Medicina (D.A.d.S.), Universidade de Lisboa, Lisbon, Portugal; Department of Neurology (J.D., R.L.), Leuven University Hospital, Belgium; International Clinical Research Center and Department of Neurology (R.M.), St. Anne´s University Hospital in Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Neurology (P.V.), Groeninge Hospital, Kortrijk; Department of Neurology (P.V.), University Hospitals Antwerp; Department of Translational Neuroscience (P.V.), University of Antwerp, Belgium; Department of Neurology (J.E.S., T.G.J.), Cooper Neurological Institute, Cooper University Hospital, Camden, New Jersey; Department of Neurology and Neurosurgery (J. Kõrv), University of Tartu, Estonia; Department of Neurology (J.B., R.V.,S.R.), Loyola University Chicago Stritch School of Medicine, Illinois; Department of Neurosurgery (C.W.L.), Kaiser Permanente Fontana Medical Center; Department of Neurology (N.S.S.), Kaiser Permanente Los Angeles Medical Center; Department of Neurology (A.M.Z., S.A.S.), UT Health McGovern Medical School, Houston, Texas; Department of Neurology (A.L.Z.), Medical University of South Carolina, Charleston; Department of Internal Medicine (G.N.), School of Health Sciences, University of Thessaly, Larissa, Greece; Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, Pennsylvania; Department of Neurology (A.L.), Ohio Health Riverside Methodist Hospital Columbus; Department of Medicine and Neurology (A.R.), University of Otago and Wellington Hospital, New Zealand; Department of Neurology (E.A.M.), Vanderbilt University Medical Center, Nashville, Tennessee; Department of Neurology (A.W.A., D. Alsbrook), University of Tennessee Health Center, Memphis; Department of Neurology (D.Y.H.), University of North Carolina at Chapel Hill; Departments of Neurology (S.Y.) and Radiology (E.R.), New York University Grossman School of Medicine; Douala Gynaeco-Obstetric and Pediatric Hospital (E.G.B.L.), University of Douala, Faculty of Medicine and Pharmaceutical Science, Cameroon; Ain Shams University Specialized Hospital (H.M.A., H.M.S., A.E., T.R.); Cairo University Affiliated MOH Network (F.H.); Department of Neurology (TM.), Nasser Institute for Research and Treatment, Cairo; Mansoura University Affiliated Private Hospitals Network (W.M.), Egypt; Kwame Nkrumah University of Science and Technology (F.S.S.), Kumasi, Ghana; Stroke Unit (T.O.A., K.W.), University of Ilorin Teaching Hospital; Neurology Unit (B.A.), Department of Medicine, Lagos State University Teaching Hospital; Department of Medicine (E.O.N.), Federal Medical Centre Owerri, Imo State, Nigeria; Neurology Unit (T.A.S.), Department of Medicine, Federal Medical Centre, Owo, Ondo State, Nigeria; University College Hospital (J.Y.), Ibadan, Nigeria; The National Ribat University Affiliated Hospitals (H.H.M.), Khartoum, Sudan; Neurology Section (P.B.A.), Department of Internal Medicine, Aga-Khan University, Medical College East Africa, Dar es Salaam, Tanzania; Tunis El Manar University (A.D.R.), Military Hospital of Tunis; Department of Neurology (S.B.S.), Mongi Ben Hmida National Institute of Neurology, Faculty of Medicine of Tunis, University Tunis El Manar, Tunisia; Department of Physiology (L.G.), Parirenyatwa Hospital, and Departments of Physiology and Medicine (G.W.N.), University of Zimbabwe, Harare; Department of Cerebrovascular/Endovascular Neurosurgery Division (D.S.), Erebouni Medical Center, Yerevan, Armenia; Department of Neurology (A.R.), Sir Salimulah College, Dhaka, Bangladesh; Department of Neurology (Z.A.), Taihe Hospital of Shiyan City, Hubei; Department of Neurology (F.B.), Nanyang Central Hospital, Henan; Department of Neurology (Z.D.), Wuhan No. 1 Hospital, Hubei, China; Department of Neurology (Y. Hao.), Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Department of Neurology (W.H.), Traditional Chinese Medicine Hospital of Maoming, Guangdong; Department of Neurology (G.Li.), Affiliated Hospital of Qingdao University, Shandong; Department of Neurology (W.L), The First Affiliated Hospital of Hainan Medical College; Department of Neurology (G.Liu.), Wuhan Central Hospital, Hubei; Department of Neurology (J.L.), Mianyang 404th Hospital, Sichuan; Department of Neurology (X.S.), Yijishan Hospital of Wannan Medical College, Anhui; Department of Neurology and Neuroscience (Y.S.), Shenyang Brain Institute, Shenyang First People's Hospital, Shenyang Medical College Affiliated Brain Hospital; Department of Neurology (L.T.), Affiliated Yantai Yuhuangding Hospital of Qingdao University, Shandong; Department of Neurology (H.W.), Xiangyang Central Hospital, Hubei; Department of Neurology (B.W., Y.Yan), West China Hospital, Sichuan University, Chengdu; Department of Neurology (Z.Y.), Affiliated Hospital of Southwest Medical University, Sichuan; Department of Neurology (H.Z.), Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine; Department of Neurology (J.Z.), The First Affiliated Hospital of Shandong First Medical University; Department of Neurology (W.Z.), First Affiliated Hospital of Fujian Medical University, China; Acute Stroke Unit (T.W.L.), The Prince of Wales Hospital, Kwok Tak Seng Centre for Stroke Research and Intervention, The Chinese University of Hong Kong; Interventional Neurology (C.C.), MAX Superspecialty Hospital, Saket, New Delhi; NH Institute of Neurosciences (V.H.), NH Mazumdar Shaw Medical Center, Bangalore; Department of Neurology (B.M.), Apollo Speciality Hospitals Nellore; Department of Neurology (J.D.P.), Christian Medical College, Ludhiana, Punjab; Sree Chitra Tirunal Institute for Medical Sciences and Technology (P.N.S.), Kerala, India; Stroke Unit (F.S.U.), Pelni Hospital, Jakarta, Indonesia; Neurosciences Research Center (M. Farhoudi, E.S.H.), Tabriz University of Medical Sciences, Tabriz, Iran; Beer Sheva Hospital (A.H.); Department of Interventional Neuroradiology, Rambam Healthcare Campus, Haifa, Israel (A.R., R.S.H.); Departments of Neurology (N.O.) and Neurosurgery (N.S.), Kobe City Medical Center General Hospital, Kobe; Department of Stroke and Neurovascular Surgery (D.W.), IMS Tokyo-Katsushika General Hospital; Yokohama Brain and Spine Center (R.Y.); Iwate Prefectural Central (R.D.); Department of Neurology and Stroke Treatment (N.T.), Japanese Red Cross Kyoto Daiichi Hospital; Department of Neurology (T.Y.), Kyoto Second Red Cross Hospital; Department of Neurology (T.T.), Japanese Red Cross Kumamoto Hospital; Department of Stroke Neurology (Y. Yazawa), Kohnan Hospital, Sendai; Department of Cerebrovascular Medicine (T.U.), Saga-Ken Medical Centre; Department of Neurology (T.D.), Saitama Medical Center, Kawagoe; Department of Neurology (H.S.), Nara City Hospital; Department of Neurology (Y.S.), Toyonaka Municipal Hospital, Osaka; Department of Neurology (F. Miyashita), Kagoshima City Hospital; Department of Neurology (H.F.), Japanese Red Cross Matsue Hospital, Shimane; Department of Neurology (K.M.), Shiroyama Hospital, Osaka; Department of Cerebrovascular Medicine (J.E.S.), Niigata City General Hospital; Department of Neurology (Y.S.), Sugimura Hospital, Kumamoto; Stroke Medicine (Y. Yagita), Kawasaki Medical School, Okayama; Department of Neurology (Y.T.), Osaka Red Cross Hospital; Department of Stroke Prevention and Treatment (Y.M.), Department of Neurosurgery, University of Tsukuba, Ibaraki; Department of Neurology (S.Y.), Stroke Center and Neuroendovascular Therapy, Saiseikai Central Hospital, Tokyo; Department of Neurology (R.K.), Kin-ikyo Chuo Hospital, Hokkaido; Department of Cerebrovascular Medicine (T.K.), NTT Medical Center Tokyo; Department of Neurology and Neuroendovascular Treatment (H. Yamazaki), Yokohama Shintoshi Neurosurgical Hospital; Department of Neurology (M.S.), Osaka General Medical Center; Department of Neurology (K.T.), Osaka University Hospital; Department of Advanced Brain Research (N.Y.), Tokushima University Hospital Tokushima; Department of Neurology (K.S.), Saiseikai Fukuoka General Hospital, Fukuoka; Department of Neurology (T.Y.), Tane General Hospital, Osaka; Division of Stroke (H.H.), Department of Internal Medicine, Osaka Rosai Hospital; Department of Comprehensive Stroke (I.N.), Fujita Health University School of Medicine, Toyoake, Japan; Department of Neurology (A.K.), Asfendiyarov Kazakh National Medical University; Republican Center for eHealth (K.F.), Ministry of Health of the Republic of Kazakhstan; Department of Medicine (S.K.), Al-Farabi Kazakh National University; Kazakh-Russian Medical University (M.Z.), Kazakhstan; Department of Neurology (J.-H.B.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (Y. Hwang), Kyungpook National University Hospital, School of Medicine, Kyungpook National University; Ajou University Hospital (J.S.L.); Department of Neurology (S.B.L.), Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Department of Neurology (J.M.), National Medical Center, Seoul; Department of Neurology (H.P., S.I.S.), Keimyung University School of Medicine, Dongsan Medical Center, Daegu; Department of Neurology (J.H.S.), Busan Paik Hospital, School of Medicine, Inje University, Busan; Department of Neurology (K.-D.S.), National Health Insurance Service Ilsan Hospital, Goyang; Asan Medical Center (C.J.Y.), Seoul, South Korea; Department of Neurology (R.A.), LAU Medical Center-Rizk Hospital, Beirut, Lebanon; Department of Medicine (W.A.W.Z., N.W.Y.), Pusat Perubatan Universiti Kebangsaan Malaysia, Kuala Lumpur; Sultanah Nur Zahirah (Z.A.A., K.A.I.), Kuala Terengganu; University Putra Malaysia (H.b.B.); Sarawak General Hospital, Kuching (L.W.C.); Hospital Sultan Abdul Halim (A.B.I.), Sungai Petani Kedah; Hospital Seberang Jaya (I.L.), Pulau Pinang; Thomson Hospital Kota Damansara (W.Y.T.), Malaysia; "Nicolae Testemitanu" State University of Medicine and Pharmacy (S.G., P.L.), and Department of Neurology, Emergency Medicine Institute, Chisinau, Republic of Moldova; Department of Stroke Unit (A.M.A.H.), Royal Hospital Muscat, Oman; Neuroscience Institute (Y.Z.I., N.A.), Hamad Medical Corporation, Doha, Qatar; St. Luke's Medical Center-Institute of Neurosciences (M.C.P.-F., C.O.C.), Quezon City, Philippines; Endovascular Neurosurgery (D.K.), Saint-Petersburg Dzhanelidze Research Institute of Emergency Medicine, St. Petersburg, Russia; Department of Neurology (A.A.), Stroke Unit, King Saud University, College of Medicine, Riyadh; Department of Neurosurgery (H.A.-J.), Interventional Radiology, and Critical Care Medicine, King Fahad Hospital of the University, Imam Abdulrahman bin Faisal University, Saudi Arabia; Singapore National Neuroscience Institute (C.H.T.); Changi General Hospital (M.J.M.), Singapore; Neuroscience Center, Raffles Hospital (N.V.), Singapore; Department of Neurology (C.-H.C., S.-C.T.), National Taiwan University Hospital; Department of Radiology (A.C.), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Dicle University Medical School and Hospital (E.A.), Diyarbakir; Stroke and Neurointervention Unit (O.A., A.O.O.), Eskisehir Osmangazi University; Gaziantep University Faculty of Medicine (S.G.), Turkey; Department of Neurology (S.I.H., S.J.), Neurological Institute at Cleveland Clinic Abu Dhabi, United Arab Emirates; Stroke Center (H.L.V., A.D.C.), Hue Central Hospital, Hue, Vietnam; Stroke Department (H.H.N., T.N.P.), Da Nang Hospital, Da Nang City; 115 People's Hospital (T.H.N., T.Q.N.), Ho Chi Minh City, Vietnam; Department of Neurology (T.G., C.E.), Medical University of Graz; Department of Neurology (M. K.-O.), Research Institute of Neurointervention, University Hospital Salzburg/Paracelsus Medical University, Austria; Department of Neurology (F.B., A.D.), Centre Hospitalier Universitaire de Charleroi, Belgium; Department of Neurology (S.D.B., G.V.), Sint Jan Hospital, Bruges; Department of Neurology (S.D.R.), Brussels University Hospital (UZ Brussel); Department of Neurology (N.L.), ULB Erasme Hospitals Brussels; Department of Neurology (M.P.R.), Europe Hospitals Brussels; Department of Neurology (L.Y.), Antwerp University Hospital, Belgium; Neurology Clinic (F.A., T.S.), St. Anna University Hospital, Sofia, Bulgaria; Department of Neurology (M.R.B.), Sestre Milosrdnice University Hospital, Zagreb; Department of Neurology (H.B.), Sveti Duh University Hospital, Zagreb; Department of Neurology (I.C.), General Hospital Virovitica; Department of Neurology (Z.H.), General Hospital Zabok; Department of Radiology (F. Pfeifer), University Hospital Centre Zagreb, Croatia; Regional Hospital Karlovy Vary (I.K.); Masaryk Hospital Usti nad Labem (D.C.); Military University Hospital Praha (M. Sramek); Oblastní Nemocnice Náchod (M. Skoda); Regional Hospital Pribram (H.H.); Municipal Hospital Ostrava (L.K.); Hospital Mlada Boleslav (M. Koutny); Hospital Vitkovice (D.V.); Hospital Jihlava (O.S.); General University Hospital Praha (J.F.); Hospital Litomysl (K.H.); Hospital České Budejovice (M.N.); Hospital Pisek (R.R.); Hospital Uherske Hradiste (P.P.); Hospital Prostejov (G.K.); Regional Hospital Chomutov (J.N.); Hospital Teplice (M.V.); Mining Hospital Karvina (H.B.); Thomayer Hospital Praha (D.H.); Hospital Blansko (D.T.); University Hospital Brno (R.J.); Regional Hospital Liberec (L.J.); Hospital Ceska Lipa (J.N.); Hospital Sokolov (A.N.); Regional Hospital Kolin (Z.T.); Hospital Trutnov (P. Fibrich); Hospital Trinec (H.S.); Department of Neurology (O.V.), University Hospital Ostrava, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Bispebjerg Hospital (H.K.C.), University of Copenhagen; Stroke Center (H.K.I., T.C.T.), Rigshospitalet, University of Copenhagen; Aarhus University Hospital (C.Z.S.), Aarhus; Neurovascular Center, Zealand University Hospital, University of Copenhagen (T.W.), Roskilde, Denmark; Department of Neurology and Neurosurgery (R.V.), University of Tartu, Estonia; Neurology Clinic (K.G.-P.), West Tallinn Central Hospital; Center of Neurology (T.T.), East Tallinn Central Hospital, School of Natural Sciences and Health, Tallinn University; Internal Medicine Clinic (K.A.), Pärnu Hospital, Estonia; Université Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition (C.C., F.C.); Centre Hospitalier d'Arcachon (M.D.), Gujan-Mestras; Centre Hospitalier d'Agen (J.-M.F.); Neurologie Vasculaire (L.M.) and Neuroradiologie (O.E.), Hospices Civils de Lyon, Hôpital Pierre Wertheimer, Bron; Centre Hospitalier et Universitaire de Bordeaux (E.L., F.R.); Centre Hospitalier de Mont de Marsan (B.O.); Neurologie (R.P.), Fondation Ophtalmologique Adolphe de Rothschild; Versailles Saint-Quentin-en-Yvelines University (F. Pico); Neuroradiologie Interventionelle (M.P.), Fondation Ophtalmologique Adolphe de Rothschild; Neuroradiologie Interventionelle (R.P.), Hôpitaux Universitaires de Strasbourg, France; K. Eristavi National Center of Experimental and Clinical Surgery (T.G.), Tbilisi; Department of Neurosurgery (M. Khinikadze), New Vision University Hospital, Tbilisi; Vivamedi Medical Center (M. Khinikadze), Tbilisi; Pineo Medical Ecosystem (N.L.), Tbilisi; Ivane Javakhishvili Tbilisi State University (A.T.), Tbilisi, Georgia; Department of Neurology (S.N., P.A.R.), University Hospital Heidelberg; Department of Neurology (M. Rosenkranz), Albertinen Krankenhaus, Hamburg; Department of Neurology (H.S.), Elbe Klinken Stade, University Medical Center Göttingen; Department of Neurology (T.S.), University Hospital Carl Gustav Carus, Dresden; Kristina Szabo (K.S.), Department of Neurology, Medical Faculty Mannheim, University Heidelberg, Mannheim; Klinik und Poliklinik für Neurologie (G.T.), Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany; Department of Internal Medicine (D.S.), School of Health Sciences, University of Thessaly, Larissa; Second Department of Neurology (O.K.), Stroke Unit, Metropolitan Hospital, Piraeus, Greece; University of Szeged (P.K.), Szeged; University of Pecs (L.S., G.T.), Hungary; Stroke Center (A.A.), IRCCS Istituto di Ricovero e Cura a Carattere Scientifico, Negrar, Verona; Department of Neurology (F.B.), Ospedale San Paolo, Savona,; Institute of Neurology (P.C., G.F.), Fondazione Policlinico Universitario Agostino Gemelli, Rome; Interventional Neurovascular Unit (L.R.), Careggi University Hospital, Florence; Stroke Unit (D.S.), Azienda Socio Sanitaria Territoriale (ASST) di Lecco, Italy; Maastricht University Medical Center; Department of Neurology (M.U.), Radiology, University Medical Center Groningen; Department of Neurology (I.v.d.W.), Haaglanden Medical Center, the Hague, the Netherlands; Department of Neurology (E.S.K.), Akershus University Hospital, Lørenskog, General Practice, HELSAM, University of Oslo, Norway; Neurological Ward with Stroke Unit (W.B.), Specialist Hospital in Konskie, Gimnazjalna, Poland and Collegium Medicum, Jan Kochanowski University, Kielce, Poland; Neurological Ward with Stroke Unit (M.F.), District Hospital in Skarzysko-Kamienna; Department of Neurology (E.H.L.), Szpitala im T. Marciniaka in Wroclaw; 2nd Department of Neurology (M. Karlinski), Institute of Psychiatry and Neurology, Warsaw; Department of Neurology and Cerebrovascular Disorders (R.K., P.K.), Poznan University of Medical Sciences; 107th Military Hospital with Polyclinic (M.R.), Walcz; Department of Neurology (R.K.), St. Queen Jadwiga, Clinical Regional Hospital No. 2, Rzeszow; Department of Neurology (P.L.), Medical University of Lublin; 1st Department of Neurology (H.S.-J.), Institute of Psychiatry and Neurology, Warsaw; Department of Neurology and Stroke Unit (P.S.), Holy Spirit Specialist Hospital in Sandomierz, Collegium Medicum Jan Kochanowski University in Kielce; Copernicus PL (W.F.), Neurology and Stroke Department, Hospital M. Kopernik, Gdansk; Stroke Unit (M.W.), Neurological Department, Stanislaw Staszic University of Applied Sciences, Pila, Poland; Hospital São José (Patricia Ferreira), Centro Hospitalar Universitário de Lisboa Central, Lisbon; Stroke Unit (Paulo Ferreira, V.T.C.), Hospital Pedro Hispano, Matosinhos; Stroke Unit, Internal Medicine Department (L.F.), Neuroradiology Department, Centro Hospitalar Universitário de São João, Porto; Department of Neurology (J.P.M.), Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal; Department of Neurosciences (T.P.e.M.), Hospital de Santa Maria-CHLN, North Lisbon University Hospital; Hospital São José (A.P.N.), Centro Hospitalar Universitário de Lisboa Central, Lisbon; Department of Neurology (M. Rodrigues), Hospital Garcia de Orta, Portugal; Department of Neurology (C.F.-P.), Transilvania University, Brasov, Romania; Department of Neurology (G.K., M. Mako), Faculty Hospital Trnava, Slovakia; Department of Neurology and Stroke Center (M.A.d.L., E.D.T.), Hospital Universitario La Paz, Madrid; Department of Neurology (J.F.A.), Hospital Clínico Universitario, Universidad de Valladolid; Department of Neurology (O.A.-M.), Complejo Hospitalario Universitario de Albacete; Department of Neurology (A.C.C.), Unidad de Ictus, Hospital Universitario Ramon y Cajal, Madrid; Department of Neurology (S.P.-S), Hospital Universitario Virgen Macarena & Neurovascular Research Laboratory (J.M.), Instituto de Biomedicina de Sevilla-IbiS; Rio Hortega University Hospital (M.A.T.A.), University of Valladolid; Cerebrovascular Diseases (A.R.V.), Hospital Clinic of Barcelona, Spain; Department of Neurology (M. Mazya), Karolinska University Hospital and Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Interventional Neuroradiology (G.B.), University Hospitals of Geneva; Department of Interventional and Diagnostic Neuroradiology (A.B., M.-N.P.), Radiology and Nuclear Medicine, University Hospital Basel; Department of Neurology (U.F.), University of Bern; Department of Neuroradiology (J.G.), University of Bern; Department of Neuroscience (P.L.M., D.S.), Lausanne University Hospital, Switzerland; Department of Stroke Medicine (S.B., J. Kwan), Imperial College Healthcare NHS Trust, Charing Cross Hospital, London; Department of Neurology (K.K.), Queen's Medical Centre, Nottingham University Hospitals NHS Trust, United Kingdom; Department of Neurology (A.B., A. Shuaib), University of Alberta, Edmonton; Department of Neurology (L.C., A. Shoamanesh), McMaster University, Hamilton; Department of Clinical Neurosciences and Hotchkiss Brain Institute (A.M.D., M.D.H.), University of Calgary; Department of Neurology (T.F., S.Y.), University of British Columbia, Vancouver; Mackenzie Health (J.H., C.A.S.) Richmond Hill, Ontario; Department of Neurology (H.K.), Sunnybrook Health Sciences Centre, University of Toronto; Department of Neurology (A. Mackey), Hopital Enfant Jesus, Centre Hospitalier de l'Universite Laval, Quebec City; Department of Neurology (A.P.), University of Toronto; Medicine (G.S.), St. Michael's Hospital, University of Toronto, Canada; Department of Neurosciences (M.A.B.), Hospital Dr. Rafael A. Calderon Guardia, CCSS. San Jose, Costa Rica; Neurovascular Service (J.D.B.), Hospital General San Juan de Dios, Guatemala City; Department of Neurología (L.I.P.R.), Hospital General de Enfermedades, Instituto Guatemalteco de Seguridad Social, Guatemala City, Guatemala; Department of Neurology (F.G.-R.), University Hospital Jose Eleuterio Gonzalez, Universidad Autonoma de Nuevo Leon, Mexico; Pacífica Salud-Hospital Punta Pacífica (N.N.-E., A.B., R.K.), Panama; Department of Neurology, Radiology (M.A.), University of Kansas Medical Center; Department of Neurointerventional Neurosurgery (D. Altschul), The Valley Baptist Hospital, Ridgewood, New Jersey; Palmetto General Hospital (A.J.A.-O.), Tenet, Florida; Neurology (I.B., P.K.), University Hospital Newark, New Jersey Medical School, Rutgers, Newark, New Jersey; Community Healthcare System (A.B.), Munster, Indiana; Department of Neurology (N.B., C.B.N.), California Pacific Medical Center, San Francisco; Department of Neurology (C.B.), Mount Sinai South Nassau, New York; University of Toledo (A.C.), Ohio; Department of Neurology (S.C.), University of Maryland School of Medicine, Baltimore, Maryland; Neuroscience (S.A.C.), Inova Fairfax Hospital, Virginia; Department of Neurology (H.C.), Abington Jefferson Hospital, Pennsylvania; Department of Neurology (J.H.C.), Mount Sinai South Nassau, New York; Baptist Health Medical Center (S.D.), Little Rock, Arkansas; Department of Neurology (K.D.), HCA Houston Healthcare Clearlake, Texas; Department of Neurology (T.G.D., R.S.), Erlanger, Tennessee; Wilmington North Carolina (V.T.D.); Department of Vascular and Neurointerventional Services (R.E.), St. Louis University, Missouri; Department of Neurology (M.E.), Massachusetts General Hospital, Boston; Department of Neurology, Neurosurgery, and Radiology (M.F., S.O.-G., N.R.), University of Iowa Hospitals and Clinics, Iowa City; Department of Radiology (D.F.), Swedish Medical Center, Englewood, Colorado; Department of Radiology (D.G.), Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland; Adventist Health Glendale Comprehensive Stroke Center (M.G.), Los Angeles, California; Wellstar Neuroscience Institute (R.G.), Marietta, Georgia; Department of Neurology (A.E.H.), University of Texas Rio Grande Valley-Valley Baptist Medical Center, Texas; Department of Neurology (J.H., B.V.), Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts; Department of Neurology (A.M.K.), Wayne State, Detroit, Michigan; HSHS St. John's Hospital (N.N.K.), Southern Illinois University School of Medicine, Springfield; Virginia Hospital Center (B.S.K.), Arlington; Department of Neurology, University of Michigan, Ann Arbor; Weill-Cornell Medical College (D.O.K.), New York-Presbyterian Queens; Department of Neurology (V.H.L.), Ohio State University, Columbus; Department of Neurology (L.Y.L.), Tufts Medical Center, Boston, Massachusetts; Vascular and Neurointerventional Services (G.L.), St. Louis University, Missouri; Miami Cardiac & Vascular Institute (I.L., A.K.S.), Florida; Department of Neurology (H.L.L.), Oregon Health & Science University, Portland; Department of Emergency Medicine (L.M., M.S.), Steward Holy Family Hospital, Methuen, MA; Vidant Medical Center (S.M.), Greenville, North Carolina; Department of Neurology (A.M.M., D.R.Y.) and Neurosurgery (D.R.Y.), University of Miami Miller School of Medicine, Florida; Department of Neurology (H.M.), SUNY Upstate New York, Syracuse; Memorial Neuroscience Institute (B.P.M.), Pembroke Pines, Florida; Neurosciences (J.M., J.P.T.), Spectrum Health, Michigan State University College of Medicine, Grand Rapids, Michigan; Sutter Health (M.M.), Sacramento, California; Department of Neurology (J.G.M.), Maine Medical Center, Portland; Department of Neurology (S.S.M.), Bayhealth, Dover, Delaware; Department of Neurology and Pediatrics (F.N.), Emory University, Atlanta, Georgia; Department of Neurology (K.N.), University of Arkansas for Medical Sciences, Little Rock; Department of Radiology and Neurology (R.N.-W.), UT Southwestern Medical Center, Dallas, Texas; Ascension St. John Medical Center (R.H.R.), Tulsa, Oklahoma; Riverside Regional Medical Center (P.R.), Newport, Virginia; Department of Neurology (J.R.R., T.N.N.), Boston University School of Medicine, MA; Department of Neurology (A.R.), Hospital of the University of Pennsylvania, Philadelphia; Department of Neurology (M.S.), University of Washington School Medicine, Seattle; Department of Neurology (B.S.), University of Massachusetts Medical Center, Worcester; Department of Neurology (A.S.), CHI-Immanuel Neurological Institute, Creighton University, Omaha, Nebraska; Holy Cross Hospital (S.L.S.), Fort Lauderdale, Florida; Department of Neurology (V.S.), Interventional Neuroradiology, University of California in Los Angeles; Banner Desert Medical Center (M.T.), Mesa, Arizona; Hospital de Agudos Dr. Ignacio Privano (O.B., A.L.), Argentina; Institute for Neurological Research, FLENI (V.A.P.L.), Buenos Aires, Argentina; Hospital das Clinicas/São Paulo University (M.S.A., A.C.); Sumare State Hospital (F.B.C., L.V.), São Paulo; Hospital Vera Cruz (L.D.D.S.), Deus Campinas; Irmanandade Santa Casa de Porto Alegre (L.V.G.); Stroke Unit (F.O.L., F. Mont'alverne), Hospital Geral de Fortaleza; Stroke Unit (A.L.L., P.S.C.M.), Hospital Sao Jose, Joinville, Santa Catarina; Stroke Unit (R.T.M.), Neurology, Nossa Senhora da Conceição Hospital, Porto Alegre; Department of Neurology (D.L.M.C.), Hospital Moinhos de Vento, Porto Alegre; Department of Neurology (L.C.R.), Hospital de Base do Distrito Federal; Hospital Ana (V.F.C.), Hospital Juliane, Federal University of Parana, Curitiba, Brazil; Vascular Neurology Unit (P.M.L., V.V.O.), Neurology Service, Department of Neurology and Psychiatry, Clínica Alemana, Universidad del Desarrollo, Santiago; Hospital Padre Hurtado (V.N., J.M.A.T.) Santiago, Chile; Fundación Valle del Lili (P.F.R.A.), Cali; Stroke Center (H.B.), Fundación Santa Fe de Bogotá; Department of Neurology (A.B.C.-Q.), Hospital Departamental Universitario del Quindio San Juan de Dios, Armenia; Clinica Universitaria Colombia (C.E.R.O.), Bogotá; University Hospital of San Vicente Foundation (D.K.M.B.), Medellin; Barranquilla, Colombia (O.L.); Hospital Infantil Universitario de San Jose (M.R.P.), Bogota; Stroke Unit (L.F.D.-E.), Hospital de Clínicas, Facultad de Ciencias Médicas, Universidad Nacional de Asunción; Neurology Service (D.E.D.M.F., A.C.V.), Hospital Central del Instituto de Prevision Social, Paraguay; Internal Medicine Service (A.J.Z.Z.), Hospital Central de Policia "Rigoberto Caballero", Paraguay; National Institute of Neurological Sciences of Lima Peru (D.M.B.I.); Hospital Edgardo Rebagliati Martins Lima-Peru (L.R.K.); Department of Neurology (B.C.), Royal Melbourne Hospital; Department of Neurology (G.J.H.), Sir Charles Gairdner Hospital and Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth; University of Melbourne (C.H., R.S.), Ballarat Health Service, Australia University of Melbourne; Department of Neurology (T.K.), Royal Adelaide Hospital; Department of Neurosurgery (A. Ma), Royal North Shore Hospital, Sydney; Department of Neurology (R.T.M.), Mater Hospital, Brisbane; Department of Neurology (R.S.), Austin Health, Victoria; Florey Institute of Neuroscience and Mental Health (R.S.), Parkville, Melbourne, Australia; Greymouth Base Hospital (D.S.), New Zealand; Department of Neurology (T.Y.-H.W.), Christchurch Hospital, New Zealand; Department of Neurology (D.L.), University of California in Los Angeles; and Department of Neurology (O.O.Z.), Mercy Health Neurosciences, Toledo, Ohio.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
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http://dx.doi.org/10.1212/WNL.0000000000011885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205458PMC
June 2021

Clinical Features of Patients With Cervical Artery Dissection and Fibromuscular Dysplasia.

Stroke 2021 Mar 28;52(3):821-829. Epub 2021 Jan 28.

UO Neurologia, Ospedale Villa Sofia, Palermo, Italy (V.T.).

Background And Purpose: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated.

Methods: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD-).

Results: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13-2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06-18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26-0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58-7.31] and 2.07 [95% CI, 1.06-4.03], respectively) in multivariable Cox proportional hazards analysis.

Conclusions: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence.
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http://dx.doi.org/10.1161/STROKEAHA.120.031579DOI Listing
March 2021

Hyperdense artery sign, symptomatic infarct swelling and effect of alteplase in acute ischaemic stroke.

Stroke Vasc Neurol 2021 Jun 27;6(2):238-243. Epub 2020 Nov 27.

Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK

Background: Alteplase improves functional outcomes of patients with acute ischaemic stroke, but its effects on symptomatic infarct swelling, an adverse complication of stroke and the influence of CT hyperdense artery sign (HAS) are unclear. This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association.

Methods: We included stroke patients whose prerandomisation scan was non-contrast CT. Raters, masked to clinical information, assessed baseline (prerandomisation) and follow-up (24-48 hours postrandomisation) CT scans for HAS, defined as an intracranial artery appearing denser than contralateral arteries. Symptomatic infarct swelling was defined as clinically significant neurological deterioration ≤7 days after stroke with radiological evidence of midline shift, effacement of basal cisterns or uncal herniation.

Results: Among 2961 patients, HAS presence at baseline was associated with higher risk of symptomatic infarct swelling (OR 2.21; 95% CI 1.42 to 3.44). Alteplase increased the risk of swelling (OR 1.69; 95% CI 1.11 to 2.57), with no difference between patients with and those without baseline HAS (p=0.49). In patients with baseline HAS, alteplase reduced the proportion with HAS at follow-up (OR 0.67; 95% CI 0.50 to 0.91), where HAS disappearance was associated with reduced risk of swelling (OR 0.25, 95% CI 0.14 to 0.47).

Conclusion: Although alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS, it was also associated with accelerated clearance of HAS, which in return reduced swelling, providing further mechanistic insights to underpin the benefits of alteplase.
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http://dx.doi.org/10.1136/svn-2020-000569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258046PMC
June 2021

Long-term outcome of cervical artery dissection : IPSYS CeAD: study protocol, rationale, and baseline data of an Italian multicenter research collaboration.

Neurol Sci 2020 Nov 12;41(11):3265-3272. Epub 2020 May 12.

UO Neurologia, Ospedale Villa Sofia, Palermo, Italy.

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 (t) and then annually (t at 1 year, t 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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http://dx.doi.org/10.1007/s10072-020-04464-9DOI Listing
November 2020

Seizures as the first clinical manifestation of acute pulmonary embolism: an underestimate issue in neurocritical care.

Neurol Sci 2020 Jun 10;41(6):1427-1436. Epub 2020 Feb 10.

Division of Cardiology, Rovigo General Hospital, Santa Maria della Misericordia Hospital, Via Tre Martiri 140, 45100, Rovigo, Italy.

Background: The aim of the present review is to analyze the clinical characteristics of patients with acute pulmonary embolism (PE) which seizures were the first clinical manifestation of the disease.

Methods: After screening 258 articles in PubMed, Scopus, Cochrane Library, and Google Scholar databases, we identified 16 case reports meeting the inclusion criteria.

Results: The mean age of the population was 48.4 ± 19.8 years (9 males and 7 females). About three of four patients (68.7%) were hemodynamically stable at admission, having a systolic blood pressure > 90 mmHg. Intriguingly, the doubt of acute PE was based on clinical suspicion or on instrumental findings in 62.5% and 18.7% of patients, respectively. In 3 subjects (18.7%), the acute cardiovascular disease was not suspected. Half of patients had an unremarkable previous medical history while neurological comorbidities were present in 4 patients (25.0%). During seizures, a transient loss of consciousness (TLOC) was reported in 6 cases. Seizures were retrospectively classified according to the 2017 ILAE classification, whenever possible. A focal and generalized onset was reported in 37.5% and 50% of cases, respectively, in 12.5% of patient's data that were insufficient to classify the events. The mean number of seizure episodes in the population enrolled was 2.0 ± 1.1. Mortality rate was 54.5% but one investigation did not report the patient's outcome.

Conclusions: The relationship between seizures and acute PE is probably underrecognized. Identifying patients that have a high probability of acute PE is fundamental to avoid any treatment delay and ameliorate their outcomes.
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http://dx.doi.org/10.1007/s10072-020-04275-yDOI Listing
June 2020

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

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

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

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

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

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

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

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

Left atrial enlargement as a maker of significant high-risk patent foramen ovale.

Int J Cardiovasc Imaging 2019 Nov 19;35(11):2049-2056. Epub 2019 Jul 19.

Division of Cardiology, Echocardiography Lab, Rovigo General Hospital, Rovigo, Italy.

Left atrial (LA) enlargement is a marker of LA cardiopathy and, in patients with patent foramen ovale (PFO), is associated with an increased risk of ischemic stroke. The primary study outcome was the comparison of LA diameter between patients undergoing percutaneous PFO closure versus those treated conservatively. The secondary endpoints were the association of LA diameter with the Risk of Paradoxical Emboli (ROPE) score and the presence of Atrial septal aneurysm (ASA) and Right-To-Left Shunt (RLS). Retrospective analysis of clinical and instrumental data of 1040 subjects referred to a single tertiary center for PFO evaluation and treatment. Seven hundred and nineteen patients were enrolled: 495 patients (closure group, mean RoPE score 7.6 ± 0.8) underwent PFO closure while 224 patients (control group, mean RoPE score 4.1 ± 0.9. p < 0.001) were left to medical therapy. Preoperative LA diameter was significantly larger in closure group and reduced from 44.3 ± 9.1 to 37.3 ± 4.1 mm (p = 0.01) 1 year after the procedure to the size of controls. A larger LA diameter was associated with permanent RLS, RLS curtain pattern, ASA presence and multiple ischemic brain lesions pattern at neuroimaging. A LA diameter ≥ 43 mm was a predictor a RoPEscore > 7. In our patients' cohort, LA diameter was associated with the clinic severity of PFO and RLS. The reversal of LA enlargement after PFO closure suggests a role for RLS to induce LA cardiopathy. LA enlargement has the potential to be considered per se as an indication to transcatheter PFO repair.
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http://dx.doi.org/10.1007/s10554-019-01666-xDOI Listing
November 2019

Cerebrovascular events after herpes zoster infection: a risk that should be not underestimated.

J Neurovirol 2019 08 8;25(4):439-447. Epub 2019 May 8.

Division of Neurology, Stroke Center, SacroCuore-Don Calabria Hospital, Negrar, Italy.

The occurrence of a cerebrovascular event after a herpes zoster (HZ) infection represents a nightmare in clinical practice, especially in those patients with concomitant cardiovascular comorbidities/risk factors and disease related per se to a higher risk of zoster infection. Moreover, the absence of a consensus opinion regarding a specific and adequate prevention of cerebrovascular events in these patients further complicates the treatment. Accumulating evidences demonstrated that HZ and HZ ophtalmicus (HZO) increase the risk of cerebrovascular events in the short-and long-term periods. Moreover, patient's ages < 40 years old, despite having fewer traditional cardiovascular comorbidities, demonstrated a higher risk of cerebrovascular events after both HZ and HZO infection. Further prospective studies are needed to analyse the role of antiviral treatments and vaccination in these subjects to clarify if they could be able to reduce the risk of stroke after a zoster infection. In the meanwhile, physicians must be aware of a higher risk of cerebrovascular events, especially in younger patients, with few cardiovascular risk factors, after an HZ infection.
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http://dx.doi.org/10.1007/s13365-019-00748-9DOI Listing
August 2019

The clinical spectrum of reversible cerebral vasoconstriction syndrome: The Italian Project on Stroke at Young Age (IPSYS).

Cephalalgia 2019 Sep 6;39(10):1267-1276. Epub 2019 May 6.

28 Neurologia d'Urgenza and Stroke Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano-Milano, Italy.

Introduction: To describe clinical, neuroimaging, and laboratory features of a large cohort of Italian patients with reversible cerebral vasoconstriction syndrome.

Methods: In the setting of the multicenter Italian Project on Stroke at Young Age (IPSYS), we retrospectively enrolled patients with a diagnosis of definite reversible cerebral vasoconstriction syndrome according to the International Classification of Headache Disorders (ICHD)-3 beta criteria (6.7.3 Headache attributed to reversible cerebral vasoconstriction syndrome, imaging-proven). Clinical manifestations, neuroimaging, treatment, and clinical outcomes were evaluated in all patients. Characteristics of reversible cerebral vasoconstriction syndrome without typical causes ("idiopathic reversible cerebral vasoconstriction syndrome") were compared with those of reversible cerebral vasoconstriction syndrome related to putative causative factors ("secondary reversible cerebral vasoconstriction syndrome").

Results: A total of 102 patients (mean age, 47.2 ± 13.9 years; females, 85 [83.3%]) qualified for the analysis. Thunderclap headache at presentation was reported in 69 (67.6%) patients, and it typically recurred in 42 (60.9%). Compared to reversible cerebral vasoconstriction syndrome cases related to putative etiologic conditions (n = 21 [20.6%]), patients with idiopathic reversible cerebral vasoconstriction syndrome (n = 81 [79.4%]) were significantly older (49.2 ± 13.9 vs. 39.5 ± 11.4 years), had more frequently typical thunderclap headache (77.8% vs. 28.6%) and less frequently neurological complications (epileptic seizures, 11.1% vs. 38.1%; cerebral infarction, 6.1% vs. 33.3%), as well as concomitant reversible brain edema (25.9% vs. 47.6%).

Conclusions: Clinical manifestations and putative etiologies of reversible cerebral vasoconstriction syndrome in our series are slightly different from those observed in previous cohorts. This variability might be partly related to the coexistence of precipitating conditions with a putative etiologic role on disease occurrence.
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http://dx.doi.org/10.1177/0333102419849013DOI Listing
September 2019

Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.

Neurology 2018 11 26;91(22):e2067-e2077. Epub 2018 Oct 26.

From Edinburgh Imaging, and UK Dementia Research Institute at the University of Edinburgh and Centre for Clinical Brain Sciences (G.M., Z.M., A.J.F., J.M.W.), and Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Medicine (L.C.), University of Western Australia; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Department of Neurology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy; Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.

Objective: To determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke.

Methods: The Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue appearances between baseline and follow-up imaging, and 6-month functional outcome in IST-3. We performed a meta-analysis of randomized trials of alteplase vs control with pre- and postrandomization imaging.

Results: Of 3,035 patients recruited in IST-3, 2,916 had baseline and follow-up brain imaging. Progression in either lesion extent or swelling independently predicted poorer 6-month outcome (adjusted odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.88-0.96, < 0.001; OR = 0.73, 95% CI 0.66-0.79, < 0.001, respectively). Patients allocated alteplase were less likely than controls to develop increased lesion visibility at follow-up (OR = 0.77, 95% CI 0.67-0.89, < 0.001), but there was no evidence that alteplase reduced progression of lesion extent or swelling. In meta-analysis of 6 trials including IST-3 (n = 4,757), allocation to alteplase was associated with a reduction in ischemic lesion extent on follow-up imaging (OR = 0.85, 95% CI 0.76-0.95, = 0.004).

Conclusion: Alteplase was associated with reduced short-term progression in lesion visibility. In meta-analysis, alteplase reduced lesion extent. These findings may indicate that alteplase improves functional outcome by reducing tissue damage.

Classification Of Evidence: This study provides Class II evidence that IV alteplase impedes the progression of ischemic brain lesions on imaging after stroke.
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http://dx.doi.org/10.1212/WNL.0000000000006575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282236PMC
November 2018

Intravenous thrombolysis for ischemic stroke in the Veneto region: the gap between eligibility and reality.

J Thromb Thrombolysis 2019 Jan;47(1):113-120

Stroke Unit, Ospedale Sant'Antonio, Padua, Italy.

Intravenous thrombolysis (IVT) is the treatment of choice for most patients with acute ischemic stroke. According to the recently updated guidelines, IVT should be administered in absence of absolute exclusion criteria. We aimed to assess the proportion of ischemic strokes potentially eligible and actually treated with IVT, and to explore the reasons for not administering IVT. We prospectively collected and analyzed data from 1184 consecutive ischemic stroke patients admitted to the 22 Stroke Units (SUs) of the Veneto region from September 18th to December 10th 2017. Patients were treated with IVT according to the current Italian guidelines. For untreated patients, the reasons for not administering IVT were reported by each center in a predefined model including absolute and/or relative exclusion criteria and other possible reasons. Out of 841 (71%) patients who presented within 4.5 h of stroke onset, 704 (59%) had no other absolute exclusion criteria and were therefore potentially eligible for IVT according to the current guidelines. However, only 323 (27%) patients were eventually treated with IVT. Among 861 (73%) untreated patients, 480 had at least one absolute exclusion criterion, 283 only relative exclusion criteria, 56 only other reasons, and 42 a combination of relative exclusion criteria and other reasons. Our study showed that only 46% (323/704) of the potentially eligible patients were actually treated with IVT in the SUs of the Veneto region. All healthcare professionals involved in the acute stroke pathway should make an effort to bridge this gap between eligibility and reality.
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http://dx.doi.org/10.1007/s11239-018-1753-8DOI Listing
January 2019

Migraine improvement after spontaneous cervical artery dissection the Italian Project on Stroke in Young Adults (IPSYS).

Neurol Sci 2019 Jan 21;40(1):59-66. Epub 2018 Sep 21.

Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili, 1,, 25123, Brescia, Italy.

Objective: Whether migraine modifies after spontaneous cervical artery dissection (sCeAD) more than after other stroke etiologic subtypes has never been adequately investigated.

Methods: In the setting of the Italian Project on Stroke in Young Adults (IPSYS), we compared the course of migraine before and after acute brain infarct in a group of migraine patients with sCeAD and a group of migraine patients whose ischemia was due to a cause other than CeAD (non-CeAD IS), matched by sex, age (± 3 years), and migraine subtype.We applied linear mixed models to evaluate pre-event vs post-event changes and differences between sCeAD and non-CeAD IS patients.

Results: Eighty-seven patients per group (migraine without aura/migraine with aura, 67/20) qualified for the analysis. After the acute event, migraine headaches disappeared in 14.0% of CeAD patients vs 0.0% of non-CeAD IS patients (p ≤ 0.001). Migraine frequency (patients suffering at least 1 attack, from 93.1 to 80.5%, p = 0.001), pain intensity (from 6.7 ± 1.7 to 4.6 ± 2.6 in a 0 to 10 pain scale, p ≤ 0.001), and use of acute anti-migraine medications (patients taking at least 1 preparation, from 81.6 to 64.4%, p = 0.007) also improved significantly after CeAD as opposed to that observed after non-CeAD IS.

Conclusion: The spontaneous improvement of migraine after sCeAD reinforces the hypothesis of a pathogenic link between the two conditions.
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http://dx.doi.org/10.1007/s10072-018-3578-9DOI Listing
January 2019

Electrocardiographic RR Interval Dynamic Analysis to Identify Acute Stroke Patients at High Risk for Atrial Fibrillation Episodes During Stroke Unit Admission.

Transl Stroke Res 2019 06 3;10(3):273-278. Epub 2018 Jul 3.

Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia.

Patients at short-term risk of paroxysmal atrial fibrillation (PAF) often exhibit increased RR interval variability during sinus rhythm. We studied if RR dynamic analysis, applied in the first hours after stroke unit (SU) admission, identified acute ischemic stroke patients at higher risk for subsequent PAF episodes detected within the SU hospitalization. Acute ischemic stroke patients underwent continuous cardiac monitoring (CCM) using standard bedside monitors immediately after SU admission. The CCM tracks from the first 48 h were analyzed using a telemedicine service (SRA clinic, Apoplex Medical, Germany). Based on the RR dynamics, the stroke risk analysis (SRA) algorithm stratified the risk for PAF as follows: low risk for PAF, high risk for PAF, presence of manifest AF. The subsequent presence/absence of PAF during the whole SU hospitalization was ruled out using all available CCMs, standard ECGs, or 24-h Holter ECGs. Two hundred patients (40% females, mean age 71 ± 16 years) were included. According to the initial SRA analysis, 111 patients (56%) were considered as low risk for PAF, 52 (26%) as high risk while 37 patients (18%) had manifest AF. A low-risk level SRA was associated with a reduced probability for subsequent PAF detection (1/111, 0.9%, 95% CI 0-4.3%) while a high-risk level SRA predicted an increased probability (20/52, 38.5% (95% CI 25-52%). RR dynamic analysis performed in the first hours after ischemic stroke may stratify patients into categories at low or high risk for forthcoming paroxysmal AF episodes detected within the SU hospitalization.
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http://dx.doi.org/10.1007/s12975-018-0645-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526141PMC
June 2019

Introduction of direct oral anticoagulant within 7 days of stroke onset: a nomogram to predict the probability of 3-month modified Rankin Scale score > 2.

J Thromb Thrombolysis 2018 Oct;46(3):292-298

Department of Neuroscience, Azienda Ospedaliera Universitaria Integrata, Piazzale A. Stefani 1, 37126, Verona, Italy.

In clinical practice, direct oral anticoagulants (DOACs) are often started earlier (≤ 7 days) than in randomized clinical trials after stroke. We aimed to develop a nomogram model incorporating time of DOAC introduction ≤ 7 days of stroke onset in combination with different degrees of stroke radiological/neurological severity at the time of treatment to predict the probability of unfavorable outcome. We conducted a multicenter prospective study including 344 patients who started DOAC 1-7 days after atrial fibrillation-related stroke onset. Computed tomography scan 24-36 h after stroke onset was performed in all patients before starting DOAC. Unfavorable outcome was defined as modified Rankin Scale (mRS) score > 2 at 3 months. Based on multivariate logistic model, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver operating characteristic curve (AUC-ROC) and calibration of risk prediction model by using the Hosmer-Lemeshow test. Onset-to-treatment time for DOAC (OR: 1.21, p = 0.030), NIH Stroke Scale (NIHSS) score at the time of treatment (OR: 1.00 for NIHSS = 0-5; OR: 2.67, p = 0.016 for NIHSS = 6-9; OR: 26.70, p < 0.001 for NIHSS = 10-14; OR: 57.48, p < 0.001 for NIHSS ≥ 15), size infarct (OR: 1.00 for small infarct; OR: 2.26, p = 0.023 for medium infarct; OR: 3.40, p = 0.005 for large infarct), and age ≥ 80 years (OR: 1.96, p = 0.028) remained independent predictors of unfavorable outcome to compose the nomogram. The AUC-ROC of nomogram was 0.858. Calibration was good (p = 2.889 for the Hosmer-Lemeshow test). The combination of onset-to-treatment time of DOAC with stroke radiological/neurological severity at the time of treatment and old age may predict the probability of unfavorable outcome.
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http://dx.doi.org/10.1007/s11239-018-1700-8DOI Listing
October 2018

Blood pressure variability and leukoaraiosis in acute ischemic stroke.

Int J Stroke 2018 07 5;13(5):473-480. Epub 2017 Sep 5.

2 Brain Research Imaging Centre, The University of Edinburgh, Edinburgh, UK.

Higher blood pressure, blood pressure variability, and leukoaraiosis are risk factors for early adverse events and poor functional outcome after ischemic stroke, but prior studies differed on whether leukoaraiosis was associated with blood pressure variability, including in ischemic stroke. In the Third International Stroke Trial, blood pressure was measured in the acute phase of ischemic stroke immediately prior to randomization, and at 0.5, 1, and 24 h after randomization. Masked neuroradiologists rated index infarct, leukoaraiosis, and atrophy on CT using validated methods. We characterized blood pressure variation by coefficient of variance and three other standard methods. We measured associations between blood pressure, blood pressure variability, and leukoaraiosis using generalized estimating equations, adjusting for age, and a number of covariates related to treatment and stroke type/severity. Among 3017 patients, mean (±SD) systolic and diastolic blood pressure decreased from 155(±24)/82(±15) mmHg pre-randomization to 146(±23)/78(±14) mmHg 24 h later ( P < 0.005). Mean within-subject coefficient of variance was 0.09 ± 0.05 for systolic and 0.11 ± 0.06 for diastolic blood pressure. Patients with most leukoaraiosis were older and had higher blood pressure than those with least ( P < 0.0001). Although statistically significant in simple pairwise comparisons, no measures of blood pressure variability were associated with leukoaraiosis when adjusting for confounding variables ( P > 0.05), e.g. age. Our results suggest that blood pressure variability is not a potential mechanism to explain the association between leukoaraiosis and poor outcome after acute stroke.
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http://dx.doi.org/10.1177/1747493017729267DOI Listing
July 2018

Atopic status and latex sensitization in a cohort of 1,628 students of health care faculties.

Ann Allergy Asthma Immunol 2017 05;118(5):603-607

Unit of Occupational Medicine, University of Trieste, Trieste, Italy.

Background: Atopic diseases have increased since the second half of the previous century. Atopic workers are at higher risk to be sensitized to latex, and the first years of exposure are supposed to be especially risky.

Objective: To assess atopic status and rate of latex sensitization in health care students starting their exposure to latex gloves.

Methods: We analyzed medical surveillance data from 1,628 health care students from 2010 to 2016. Students completed a questionnaire focused on their previous and current latex exposure and personal and family histories of allergic diseases; underwent skin prick testing with common allergens and latex extract (and/or total and latex-specific immunoglobulin E in serum); and underwent a medical examination.

Results: Skin prick test results for common inhalant allergens showed that 807 of 1,628 students (49.6%) had atopy. Atopy by skin prick testing was associated with male sex (odds ratio 1.49, 95% confidence interval 1.18-1.86), a personal history of oculorhinitis or asthma (odds ratio 10.22, 95% confidence interval 7.4-14.13), and atopic eczema (odds ratio 1.87, 95% confidence interval 1.05-3.36) at multivariate regression analysis. Eleven students (0.7% of total population) were found to be sensitized to latex and all had atopy.

Conclusion: Despite the high prevalence of atopy in health care students of Trieste, the latex sensitization rate is very low and comparable to general population. This is reasonably due to the low exposure to latex gloves at the time of the evaluation and to low latex release from the gloves currently used in our hospital.
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http://dx.doi.org/10.1016/j.anai.2017.03.002DOI Listing
May 2017

Association Between Migraine and Cervical Artery Dissection: The Italian Project on Stroke in Young Adults.

JAMA Neurol 2017 05;74(5):512-518

Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.

Importance: Although sparse observational studies have suggested a link between migraine and cervical artery dissection (CEAD), any association between the 2 disorders is still unconfirmed. This lack of a definitive conclusion might have implications in understanding the pathogenesis of both conditions and the complex relationship between migraine and ischemic stroke (IS).

Objective: To investigate whether a history of migraine and its subtypes is associated with the occurrence of CEAD.

Design, Setting, And Participants: A prospective cohort study of consecutive patients aged 18 to 45 years with first-ever acute ischemic stroke enrolled in the multicenter Italian Project on Stroke in Young Adults was conducted between January 1, 2000, and June 30, 2015. In a case-control design, the study assessed whether the frequency of migraine and its subtypes (presence or absence of an aura) differs between patients whose IS was due to CEAD (CEAD IS) and those whose IS was due to a cause other than CEAD (non-CEAD IS) and compared the characteristics of patients with CEAD IS with and without migraine.

Main Outcomes And Measures: Frequency of migraine and its subtypes in patients with CEAD IS vs non-CEAD IS.

Results: Of the 2485 patients (mean [SD] age, 36.8 [7.1] years; women, 1163 [46.8%]) included in the registry, 334 (13.4%) had CEAD IS and 2151 (86.6%) had non-CEAD IS. Migraine was more common in the CEAD IS group (103 [30.8%] vs 525 [24.4%], P = .01), and the difference was mainly due to migraine without aura (80 [24.0%] vs 335 [15.6%], P < .001). Compared with migraine with aura, migraine without aura was independently associated with CEAD IS (OR, 1.74; 95% CI, 1.30-2.33). The strength of this association was higher in men (OR, 1.99; 95% CI, 1.31-3.04) and in patients 39.0 years or younger (OR, 1.82; 95% CI, 1.22-2.71). The risk factor profile was similar in migrainous and non-migrainous patients with CEAD IS (eg, hypertension, 20 [19.4%] vs 57 [24.7%], P = .29; diabetes, 1 [1.0%] vs 3 [1.3%], P > .99).

Conclusions And Relevance: In patients with IS aged 18 to 45 years, migraine, especially migraine without aura, is consistently associated with CEAD. This finding suggests common features and warrants further analyses to elucidate the underlying biologic mechanisms.
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http://dx.doi.org/10.1001/jamaneurol.2016.5704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822194PMC
May 2017

Arterial Obstruction on Computed Tomographic or Magnetic Resonance Angiography and Response to Intravenous Thrombolytics in Ischemic Stroke.

Stroke 2017 02 22;48(2):353-360. Epub 2016 Dec 22.

From the Division of Neuroimaging Sciences (G.M., A.J.F., R.J.S., E.S., J.P., J.M.W.) and Division of Clinical Neurosciences (D.P., P.A.G.S.), University of Edinburgh, United Kingdom; Department of Neuroradiology, Dresden University Stroke Centre, Germany (R.v.K.); Stroke Center, Sacro Cuore-Don Calabria Hospital, Verona, Italy (A.A.); Stroke Research Group, Newcastle upon Tyne, United Kingdom (P.M.W.); National Hospital for Neurology and Neurosurgery, London, United Kingdom (M.E.A.); Neurovascular Research Group, Royal Melbourne Hospital, Australia (B.Y.); Calgary Stroke Program, Hotchkiss Brain Institute, University of Calgary, Canada (A.M.D.); and Westmead Hospital Clinical School and The George Institute for Global Health, University of Sydney, Australia (R.I.L.).

Background And Purpose: Computed tomographic angiography and magnetic resonance angiography are used increasingly to assess arterial patency in patients with ischemic stroke. We determined which baseline angiography features predict response to intravenous thrombolytics in ischemic stroke using randomized controlled trial data.

Methods: We analyzed angiograms from the IST-3 (Third International Stroke Trial), an international, multicenter, prospective, randomized controlled trial of intravenous alteplase. Readers, masked to clinical, treatment, and outcome data, assessed prerandomization computed tomographic angiography and magnetic resonance angiography for presence, extent, location, and completeness of obstruction and collaterals. We compared angiography findings to 6-month functional outcome (Oxford Handicap Scale) and tested for interactions with alteplase, using ordinal regression in adjusted analyses. We also meta-analyzed all available angiography data from other randomized controlled trials of intravenous thrombolytics.

Results: In IST-3, 300 patients had prerandomization angiography (computed tomographic angiography=271 and magnetic resonance angiography=29). On multivariable analysis, more extensive angiographic obstruction and poor collaterals independently predicted poor outcome (P<0.01). We identified no significant interaction between angiography findings and alteplase effect on Oxford Handicap Scale (P≥0.075) in IST-3. In meta-analysis (5 trials of alteplase or desmoteplase, including IST-3, n=591), there was a significantly increased benefit of thrombolytics on outcome (odds ratio>1 indicates benefit) in patients with (odds ratio, 2.07; 95% confidence interval, 1.18-3.64; P=0.011) versus without (odds ratio, 0.88; 95% confidence interval, 0.58-1.35; P=0.566) arterial obstruction (P for interaction 0.017).

Conclusions: Intravenous thrombolytics provide benefit to stroke patients with computed tomographic angiography or magnetic resonance angiography evidence of arterial obstruction, but the sample was underpowered to demonstrate significant treatment benefit or harm among patients with apparently patent arteries.

Clinical Trial Registration: URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518.
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http://dx.doi.org/10.1161/STROKEAHA.116.015164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266422PMC
February 2017

Propensity Score-Based Analysis of Percutaneous Closure Versus Medical Therapy in Patients With Cryptogenic Stroke and Patent Foramen Ovale: The IPSYS Registry (Italian Project on Stroke in Young Adults).

Circ Cardiovasc Interv 2016 09;9(9)

From the Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Italia (A.Pezzini, P. Costa, L.P. A.M., V.D.G., S.B., A. Padovani); Dipartimento di Scienze del Sistema Nervoso e del Comportamento, Unità di Statistica Medica e Genomica, Università di Pavia, Italia (M. Grassi, D.G.); Centro Trombosi, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia (C.L., P.F.); Stroke Unit, Azienda Ospedaliera Sant'Andrea, Università "La Sapienza," Roma, Italia (R.P., A.S., M.R., S.L.S.); Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova, Italia (C.G., D.M.); Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile "S. Agostino Estense," AUSL Modena, Italia (A.Z., A.M.S.); Unità di Neurologia, Ospedale di Circolo, Università dell'Insubria, Varese, Italia (M.L.D.); Stroke Unit, Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italia (M.P., C.D.); Unità di Neurologia, Ospedale Galliera, Genova, Italia (M.D.S.); U.O.C. Neurologia, A.O Universitaria "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italia (A.T.); Dipartimento di Neuroscienze, Scienze Psichiatriche e Anestesiologiche, Clinica Neurologica, Università di Messina, Italia (R.M.); IRCCS, Centro Neurolesi Bonino-Pulejo, Messina, Italia (R.S.C.); UO Neurologia, Azienda Ospedaliera-Universitaria Borgo Trento, Verona, Italia (P.B., G.T.); Stroke Center, Dipartimento di Neurologia, Ospedale Sacro Cuore Negrar, Verona, Italia (A.A.); Stroke Unit, Dipartimento di Neuroscienze, Azienda Ospedaliera Carlo Poma, Mantova, Italia (G.S.); U.O Neurologia, Istituti Ospitalieri, Cremona, Italia (M.S.); Stroke Unit, IRCCS Fondazione Istituto "C. Mondino," Pavia, Italia (A. Cavallini); Neurologia d'Urgenza e Stroke Unit, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia (S.M.); Stroke Unit, U.O Neurologia, Ospedale "S. Chiara," Trento, Italia (D.M.B.); U.O.C Neurologia, Ospedale Vald

Background: We sought to compare the benefit of percutaneous closure to that of medical therapy alone for the secondary prevention of embolism in patients with patent foramen ovale (PFO) and otherwise unexplained ischemic stroke, in a propensity scored study.

Methods And Results: Between 2000 and 2012, we selected consecutive first-ever ischemic stroke patients aged 18 to 45 years with PFO and no other cause of brain ischemia, as part of the IPSYS registry (Italian Project on Stroke in Young Adults), who underwent either percutaneous PFO closure or medical therapy for comparative analysis. Primary end point was a composite of ischemic stroke, transient ischemic attack, or peripheral embolism. Secondary end point was brain ischemia. Five hundred and twenty-one patients qualified for the analysis. The primary end point occurred in 15 patients treated with percutaneous PFO closure (7.3%) versus 33 patients medically treated (10.5%; hazard ratio, 0.72; 95% confidence interval, 0.39-1.32; P=0.285). The rates of the secondary end point brain ischemia were also similar in the 2 treatment groups (6.3% in the PFO closure group versus 10.2% in the medically treated group; hazard ratio, 0.64; 95% confidence interval, 0.33-1.21; P=0.168). Closure provided a benefit in patients aged 18 to 36 years (hazard ratio, 0.19; 95% confidence interval, 0.04-0.81; P=0.026) and in those with a substantial right-to-left shunt size (hazard ratio, 0.19; 95% confidence interval, 0.05-0.68; P=0.011).

Conclusions: PFO closure seems as effective as medical therapy for secondary prevention of cryptogenic ischemic stroke. Whether device treatment might be more effective in selected cases, such as in patients younger than 37 years and in those with a substantial right-to-left shunt size, deserves further investigation.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.115.003470DOI Listing
September 2016

Continuing versus Stopping Prestroke Antihypertensive Therapy in Acute Intracerebral Hemorrhage: A Subgroup Analysis of the Efficacy of Nitric Oxide in Stroke Trial.

J Stroke Cerebrovasc Dis 2016 May 4;25(5):1017-1026. Epub 2016 Feb 4.

Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, United Kingdom. Electronic address:

Background And Purpose: More than 50% of patients with acute intracerebral hemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial.

Methods: ENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood, cognition, and quality of life.

Results: Blood pressure level (baseline 171/92 mmHg) fell in both groups but was significantly lower at 7 days in those patients assigned to continue antihypertensive drugs (difference 9.4/3.5 mmHg, P < .01). At 90 days, the primary outcome did not differ between the groups; the adjusted common odds ratio (OR) for worse outcome with continue versus stop drugs was .92 (95% confidence interval, .45-1.89; P = .83). There was no difference between the treatment groups for any secondary outcome measure, or rates of death or serious adverse events.

Conclusions: Among patients with acute ICH, immediate continuation of antihypertensive drugs during the first week did not reduce death or major disability in comparison to stopping treatment temporarily.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851456PMC
May 2016

Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke.

Neurology 2016 Jan 9;86(2):118-25. Epub 2015 Dec 9.

From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.

Objective: To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3).

Methods: All prerandomization and follow-up (24-48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518).

Results: HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167).

Conclusions: IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS.

Classification Of Evidence: This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.
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http://dx.doi.org/10.1212/WNL.0000000000002236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731690PMC
January 2016

Glyceryl Trinitrate for Acute Intracerebral Hemorrhage: Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis.

Stroke 2016 Jan 8;47(1):44-52. Epub 2015 Dec 8.

From the Stroke Trials Unit, Division of Clinical Neuroscience (K.K., P.S., L.W., N.S., P.M.B.) and Radiological Sciences Research Group, Division of Clinical Neuroscience (R.A.D.), University of Nottingham, Nottingham, United Kingdom; Stroke Centre, Ospedale Sacro Cuore, Verona, Italy (A.A.); Department of Medical Imaging, College of Medicine, The University of Arizona, Tucson (J.L.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Australia (L.A.C.); Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Western General Hospital, Edinburgh, United Kingdom (A.M.C., J.M.W.); Stroke Unit, Santa Maria Hospital, University of Perugia, Perugia, Italy (V.C.); Department of Pharmacology, National University of Singapore, Singapore, Singapore (C.C.); Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark (H.C.); Stroke Service, Adelaide and Meath Hospital, Tallaght, Dublin, Ireland (R.C.); Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland (A.C.); Department of Medicine, Hawke's Bay Hospital, Hastings, New Zealand (J.G.); Department of Neuroradiology, Nottingham University Hospitals, Queen's Medical Centre, Nottingham, United Kingdom (P.K.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (K.R.L.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); Department of Neurology, Selcuk University Medical Faculty, Konya, Turkey (S.O.); Division of Neurology, Dalhousie University, Halifax, Canada (S.J. Phillips); Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom (S.J. Pocock); Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka (A.d.S.); and Department of Neurology, Clinical County Emergency Hospital, Targu Mures, Romania (S.S.).

Background And Purpose: The Efficacy of Nitric Oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset.

Methods: In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days.

Results: Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference -7.5/-4.2 mm Hg; both P≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04; 95% confidence interval, 0.78-1.37; P=0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22; 95% confidence interval, 0.07-0.69; P=0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN.

Conclusions: In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies.

Clinical Trial Registration: URL: http://www.isrctn.com/ISRCTN99414122. Unique identifier: 99414122.
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http://dx.doi.org/10.1161/STROKEAHA.115.010368DOI Listing
January 2016

Performance characteristics of methods for quantifying spontaneous intracerebral haemorrhage: data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial.

J Neurol Neurosurg Psychiatry 2015 Nov 9;86(11):1258-66. Epub 2015 Jan 9.

Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Western General Hospital, Edinburgh, UK.

Background: Poor prognosis after intracerebral haemorrhage (ICH) is related to haemorrhage characteristics. Along with developing therapeutic interventions, we sought to understand the performance of haemorrhage descriptors in large clinical trials.

Methods: Clinical and neuroimaging data were obtained for 548 participants with ICH from the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Independent observers performed visual categorisation of the largest diameter, measured volume using ABC/2, modified ABC/2, semiautomated segmentation (SAS), fully automatic measurement methods; shape, density and intraventricular haemorrhage were also assessed. Intraobserver and interobserver reliability were determined for these measures.

Results: ICH volume was significantly different among standard ABC/2, modified ABC/2 and SAS: (mean) 12.8 (SD 16.3), 8.9 (9.2), 12.8 (13.1) cm(3), respectively (p<0.0001). There was excellent agreement for haemorrhage volume (n=193): ABC/2 intraobserver intraclass correlation coefficient (ICC) 0.96-0.97, interobserver ICC 0.88; modified ABC/2 intraobserver ICC 0.95-0.97, interobserver ICC 0.91; SAS intraobserver ICC 0.95-0.99, interobserver ICC 0.93; largest diameter: (visual) interadjudicator ICC 0.82, (visual vs measured) adjudicator vs observer ICC 0.71; shape intraobserver ICC 0.88 interobserver ICC 0.75; density intraobserver ICC 0.86, interobserver ICC 0.73. Graeb score (mean 3.53) and modified Graeb (5.22) scores were highly correlated. Using modified ABC/2, ICH volume was underestimated in regular (by 2.2-2.5 cm(3), p<0.0001) and irregular-shaped haemorrhages (by 4.8-4.9 cm(3), p<0.0001). Fully automated measurement of haemorrhage volume was possible in only 5% of cases.

Conclusions: Formal measurement of haemorrhage characteristics and visual estimates are reproducible. The standard ABC/2 method is superior to the modified ABC/2 method for quantifying ICH volume.

Clinical Trial Registration: ISRCTN9941422.
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http://dx.doi.org/10.1136/jnnp-2014-309845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680163PMC
November 2015

Determinants of premature familial arterial thrombosis in patients with juvenile ischaemic stroke. The Italian Project on Stroke in Young Adults (IPSYS).

Thromb Haemost 2015 Mar 20;113(3):641-8. Epub 2014 Nov 20.

Alessandro Pezzini, Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italia, Tel: +39.030.3384086, Fax: +39.030. 3384086, E-mail:

Factors predicting family history (FH) of premature arterial thrombosis in young patients with ischaemic stroke (IS) have not been extensively investigated, and whether they might influence the risk of post-stroke recurrence is still unknown. In the present study we analysed 1,881 consecutive first-ever IS patients aged 18-45 years recruited from January 2000 to January 2012 as part of the Italian Project on Stroke in Young Adults (IPSYS). FH of premature arterial thrombosis was any thrombotic event [IS, myocardial infarction or other arterial events event] < 45 years in proband's first-degree relatives. Compared with patients without FH of premature arterial thrombosis, those with FH (n = 85) were more often smokers (odds ratio [OR], 1.94; 95 % confidence interval [CI], 1.21-3.09) and carriers of procoagulant abnormalities (OR, 3.66; 95 % CI, 2.21-6.06). Smoking (OR, 2.48; 95 % CI, 1.20-5.15), the A1691 mutation in factor V gene (OR, 3.64; 95 % CI, 1.31-10.10), and the A20210 mutation in the prothrombin gene (OR, 8.40; 95 % CI 3.35-21.05) were associated with FH of premature stroke (n = 33), while circulating anti-phospholipids to FH of premature myocardial infarction (n = 45; OR, 3.48; 95 % CI, 1.61-7.51). Mean follow-up time was 46.6 ± 38.6 months. Recurrent events occurred more frequently in the subgroup of patients with FH of premature stroke [19.4 %); p = 0.051] compared to patients without such a FH. In conclusion, young IS patients with FH of premature arterial thrombosis exhibit a distinct risk-factor profile, an underlying procoagulant state and have worse vascular prognosis than those with no FH of juvenile thrombotic events.
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http://dx.doi.org/10.1160/TH14-06-0566DOI Listing
March 2015

Observer reliability of CT angiography in the assessment of acute ischaemic stroke: data from the Third International Stroke Trial.

Neuroradiology 2015 Jan 7;57(1):1-9. Epub 2014 Oct 7.

Division of Neuroimaging Sciences, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.

Introduction: CT angiography (CTA) is often used for assessing patients with acute ischaemic stroke. Only limited observer reliability data exist. We tested inter- and intra-observer reliability for the assessment of CTA in acute ischaemic stroke.

Methods: We selected 15 cases from the Third International Stroke Trial (IST-3, ISRCTN25765518) with various degrees of arterial obstruction in different intracranial locations on CTA. To assess inter-observer reliability, seven members of the IST-3 expert image reading panel (>5 years experience reading CTA) and seven radiology trainees (<2 years experience) rated all 15 scans independently and blind to clinical data for: presence (versus absence) of any intracranial arterial abnormality (stenosis or occlusion), severity of arterial abnormality using relevant scales (IST-3 angiography score, Thrombolysis in Cerebral Infarction (TICI) score, Clot Burden Score), collateral supply and visibility of a perfusion defect on CTA source images (CTA-SI). Intra-observer reliability was assessed using independently repeated expert panel scan ratings. We assessed observer agreement with Krippendorff's-alpha (K-alpha).

Results: Among experienced observers, inter-observer agreement was substantial for the identification of any angiographic abnormality (K-alpha = 0.70) and with an angiography assessment scale (K-alpha = 0.60-0.66). There was less agreement for grades of collateral supply (K-alpha = 0.56) or for identification of a perfusion defect on CTA-SI (K-alpha = 0.32). Radiology trainees performed as well as expert readers when additional training was undertaken (neuroradiology specialist trainees). Intra-observer agreement among experts provided similar results (K-alpha = 0.33-0.72).

Conclusion: For most imaging characteristics assessed, CTA has moderate to substantial observer agreement in acute ischaemic stroke. Experienced readers and those with specialist training perform best.
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http://dx.doi.org/10.1007/s00234-014-1441-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295028PMC
January 2015

Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults.

Circulation 2014 Apr 7;129(16):1668-76. Epub 2014 Feb 7.

Dipartimento di Scienze Mediche e Chirurgiche, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia (A. Pezzini, P.C., L.P., A.M., V.D.G., A. Padovani; Dipartimento di Scienze del Sistema Nervoso e del Comportamento, Unità di Statistica Medica e Genomica, Università di Pavia, Pavia, Italia (M.G.); Centro Trombosi, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia (C.L., P.F.); Stroke Unit, Azienda Ospedaliera Sant'Andrea, Roma, Italia (R.P., A.S., M.R.); Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova, Genova, Italia (C.G., D.M.); Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile "S. Agostino Estense", AUSL Modena, Italia (A.Z., A.M.S.); Unità di Neurologia, Ospedale di Circolo, Università dell'Insubria, Varese, Italia (M.L.D.); Stroke Unit, Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italia (M.P.); Unità di Neurologia, Ospedale S. Andrea, La Spezia, Italia (M.D.S.); U.O.C. Neurologia, A.O Universitaria "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italia (A.T.); Dipartimento di Neuroscienze, Scienze Psichiatriche e Anestesiologiche, Clinica Neurologica, Università di Messina, Messina, Italia (R.M.); Istituto di Ricovero e Cura a Carattere Scientifico, Centro Neurolesi Bonino-Pulejo, Messina, Italia (R.S.C.); UO Neurologia, Azienda Ospedaliera-Universitaria Borgo Trento, Verona, Italia (P.B.); Stroke Center, Dipartimento di Neurologia, Ospedale Sacro Cuore Negrar, Verona, Italia (A.A.); Stroke Unit, U.O Neurologia, Azienda Ospedaliera "C. Poma", Mantova, Italia (G.S.); Stroke Unit, U.O Neurologia, IRCCS Ospedale S. Raffaele, Milano, Italia (M.S., G.G.); U.C Malattie Cerebrovascolari e Stroke Unit (A.C.) and U.C Neurologia d'Urgenza (G.M.), IRCCS Fondazione Istituto Neurologico Nazionale "C. Mondino," Pavia, Italia; Neurologia d'Urgenza and Stroke Unit, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia (S.M.); Stroke Un

Background: Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited.

Methods And Results: We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%-17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%-17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%-1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% confidence interval, 0.61-0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65).

Conclusions: Among patients with ischemic stroke aged 18 to 45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors. The IPSYS score may serve as a simple tool for risk estimation.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.113.005663DOI Listing
April 2014

Investigating the mechanisms of cardiovascular and cerebrovascular regulation in orthostatic syncope through an information decomposition strategy.

Auton Neurosci 2013 Nov 27;178(1-2):76-82. Epub 2013 Mar 27.

Department Physics and BIOtech Center, University of Trento, Trento, Italy. Electronic address:

Some previous evidence suggests that postural related syncope is associated with defective mechanisms of cerebrovascular (CB) and cardiovascular (CV) control. We characterized the information processing in short-term CB regulation, from the variability of mean cerebral blood flow velocity (CBFV) and mean arterial pressure (AP), and in CV regulation, from the variability of heart period (HP) and systolic AP (SAP), in ten young subjects developing orthostatic syncope in response to prolonged head-up tilt testing. We exploited a novel information-theoretic approach that decomposes the information associated with a variability series into three amounts: the information stored in the series, the information transferred to the series from another series, and the information unexplained by the knowledge of both series. With this approach we were able to show that, compared with the first minutes after head-up tilt, in the period preceding the syncope event (i) the information stored in CBFV variability decreased significantly while the information transferred to CBFV from AP variability increased significantly; (ii) the information storage of HP was kept high but the information transferred to HP from SAP variability decreased significantly. These patterns of information processing suggest that presyncope occurs with a loss both of CB regulation, described by the reduced ability of CBFV of buffering AP fluctuations, and of CV regulation, described by the reduced baroreflex modulation from SAP to HP. We believe that the utilization of tools from the field of information dynamics may give an integrated view of the mechanisms of CB and CV regulation in normal and diseased states, and also provide a deeper understanding of findings revealed by more traditional techniques.
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http://dx.doi.org/10.1016/j.autneu.2013.02.013DOI Listing
November 2013
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