Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

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 Redfors^{14

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 Lindgren^{30

31}, José Ferro¹³, Steven Kittner^{32

33}, Franz Fazekas³⁴, Eva Gerdts², Turgut Tatlisumak^{1

14

15}

Affiliations

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.

PMID: 31008307
PMCID: PMC6453214
DOI: 10.1177/2396987317703210

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

Jukka Putaala et al. Eur Stroke J. 2017 Jun.

. 2017 Jun;2(2):116-125.

doi: 10.1177/2396987317703210. Epub 2017 Apr 4.

Authors

Affiliations

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.

PMID: 31008307
PMCID: PMC6453214
DOI: 10.1177/2396987317703210

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.

Keywords: Brain infarction; echocardiography; electrocardiography; embolism; middle aged; paradoxical embolism; patent foramen ovale; prognosis; risk factors; stroke; thrombosis; young adult.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

**Figure 1.**
Countries and centres currently enrolling participants for SECRETO.

See this image and copyright information in PMC

References

1. Feigin VL, Lawes CM, Bennett DA, et al. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 2009; 8: 355–369. - PubMed
1. Bejot Y, Delpont B, Giroud M. Rising stroke incidence in young adults: more epidemiological evidence, more questions to be answered. J Am Heart Assoc 2016; 5: pii: e003661. doi: 10.1161/JAHA.116.003661. - PMC - PubMed
1. Ferro JM, Massaro AR, Mas JL. Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol 2010; 9: 1085–1096. - PubMed
1. Yesilot Barlas N, Putaala J, Waje-Andreassen U, et al. Etiology of first-ever ischaemic stroke in European young adults: the 15 Cities Young Stroke Study. Eur J Neurol 2013; 20: 1431–1439. - PubMed
1. Rolfs A, Fazekas F, Grittner U, et al. Acute cerebrovascular disease in the young: the Stroke in Young Fabry Patients study. Stroke 2013; 44: 340–349. - PubMed

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Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

Affiliations

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

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