@article{3108607, title = "Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design", author = "Putaala, J. and Martinez-Majander, N. and Saeed, S. and Yesilot, N. and Jäkälä, P. and Nerg, O. and Tsivgoulis, G. and Numminen, H. and Gordin, D. and von Sarnowski, B. and Waje-Andreassen, U. and Ylikotila, P. and Roine, R.O. and Zedde, M. and Huhtakangas, J. and Fonseca, C. and Redfors, P. and de Leeuw, F.-E. and Pezzini, A. and Kõrv, J. and Schneider, S. and Tanislav, C. and Enzinger, C. and Jatuzis, D. and Siegerink, B. and Martínez-Sánchez, P. and Grau, A.J. and Palm, F. and Groop, P.-H. and Lanthier, S. and Ten Cate, H. and Pussinen, P. and Paju, S. and Sinisalo, J. and Lehto, M. and Lindgren, A. and Ferro, J. and Kittner, S. and Fazekas, F. and Gerdts, E. and Tatlisumak, T.", journal = "European Stroke Journal", year = "2017", volume = "2", number = "2", pages = "116-125", publisher = "SAGE Publications Ltd", issn = "2396-9873, 2396-9881", doi = "10.1177/2396987317703210", keywords = "acute coronary syndrome; adult; Article; brain hemorrhage; brain ischemia; cardiac imaging; case control study; controlled clinical trial; controlled study; deep vein thrombosis; echocardiography; electrocardiography; follow up; gene expression; human; major clinical study; migraine with aura; mortality; multicenter study; next generation sequencing; paradoxical embolism; priority journal; prognosis; prospective study; risk factor; transient ischemic attack", 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. © 2017, © European Stroke Organisation 2017." }