Jukka Putaala1, Nicolas Martinez-Majander1, Sahrai Saeed2, Nilufer Yesilot3, Pekka Jäkälä4, Ossi Nerg4, Georgios Tsivgoulis5, Heikki Numminen6, Daniel Gordin7, Bettina von Sarnowski8, Ulrike Waje-Andreassen9, Pauli Ylikotila10, Risto O Roine10, Marialuisa Zedde11, Juha Huhtakangas12, Catarina Fonseca13, Petra Redfors14,15, Frank-Erik de Leeuw16, Alessandro Pezzini17, Janika Kõrv18, Siim Schneider19, Christian Tanislav20, Christian Enzinger21, Dalius Jatuzis22, Bob Siegerink23, Patricia Martínez-Sánchez24, Armin J Grau25, Frederick Palm25, Per-Henrik Groop7, Sylvain Lanthier26, Hugo Ten Cate27, Pirkko Pussinen28, Susanna Paju28, Juha Sinisalo29, Mika Lehto29, Arne Lindgren30,31, José Ferro13, Steven Kittner32,33, Franz Fazekas34, Eva Gerdts2, Turgut Tatlisumak1,14,15. 1. Department of Neurology, Helsinki University Hospital, Finland. 2. Department of Clinical Science, University of Bergen, Norway. 3. Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Turkey. 4. Neuro Center, Kuopio University Hospital, Finland. 5. Second Department of Neurology, National and Kapodistrian University of Athens, Attikon University Hospital, Greece. 6. Department of Neuroscience and Rehabilitation, Tampere University Hospital, Finland. 7. Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, Finland. 8. Department of Neurology, Ernst-Moritz-Arndt University Medicine, Germany. 9. Department of Neurology, Haukeland University Hospital, Norway. 10. Division of Clinical Neurosciences, Turku University Hospital, University of Turku, Finland. 11. Department of Neurology, Arcispedale S. Maria Nuova, Italy. 12. Department of Neurology, Oulu University Hospital, Finland. 13. Department of Neurosciences (Neurology), Hospital de Santa Maria, University of Lisbon, Portugal. 14. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden. 15. Department of Neurology, Sahlgrenska University Hospital, Sweden. 16. Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University Medical Center, The Netherlands. 17. Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Italy. 18. Department of Neurology and Neurosurgery, University of Tartu, Estonia. 19. North Estonia Medical Centre, Tallinn, Estonia. 20. Department of Neurology, Justus Liebig University, Germany. 21. Division of Neuroradiology, Vascular and Interventional Radiology, Medical University of Graz, Austria. 22. Department of Neurology and Neurosurgery, Center for Neurology, Vilnius University, Lithuania. 23. Centre for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Germany. 24. Department of Neurology and Stroke Centre, IdiPAZ Health Research Institute, La Paz University Hospital, Autonoma of Madrid University, Spain. 25. Department of Neurology, Klinikum Ludwigshafen, Germany. 26. Division of Neurology and Research Centre, Centre Hospitalier de l'Université de Montréal (CHUM), Canada. 27. Department of Internal Medicine, Cardiovascular Research Institute Maastricht, The Netherlands. 28. Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Finland. 29. Department of Cardiology, Heart and Lung Center, Helsinki University Hospital, Finland. 30. Department of Clinical Sciences Lund, Neurology, Lund University, Sweden. 31. Department of Neurology and Rehabilitation Medicine, Skåne University Hospital, Lund, Sweden. 32. Department of Neurology, Baltimore Veterans Administration Hospital, USA. 33. University of Maryland, USA. 34. Department of Neurology, Medical University of Graz, Austria.
Abstract
BACKGROUND: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. KEY HYPOTHESES/AIMS: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. DESIGN: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case-control study enrolling patients aged 18-49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient-control pairs enrolled by the end of 2018. SUMMARY: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.
BACKGROUND: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. KEY HYPOTHESES/AIMS: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. DESIGN: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case-control study enrolling patients aged 18-49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient-control pairs enrolled by the end of 2018. SUMMARY: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.
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