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

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 patientcontrol 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.

Diastolic function in young patients with cryptogenic stroke: A case–control pilot study

“…Revealing the Etiology, Triggers, and Outcome study (SECRETO, NCT01934725), which is an international prospective multicentre case-control study of young adults (age 18-49) with a first-ever ischaemic stroke of undetermined aetiology. The study protocol has earlier been published in more detail (Putaala et al, 2017).…”

Left ventricular non-compaction as a potential source for cryptogenic ischemic stroke in the young: A case-control study

“…Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is an international prospective multicenter case-control study of young adults (age 18-49) presenting with an imaging-positive first-ever ischemic stroke of undetermined etiology. The main study protocol has been published in more detail previously [13]. Briefly, patients are included after standardized and timely diagnostic procedures, including brain magnetic resonance imaging, imaging of intracranial and extra-cranial vessels with either computed tomography angiography or magnetic resonance angiography, and cardiac imaging to rule out established causes of ischemic stroke.…”

“…As a major strength, our case-control study was based on prospectively enrolled patients with thorough baseline characterization for both cases and controls, including structural and standardized echocardiography protocol [13,14]. Another strength is that the semi-automatic assessment of non-compacted LV mass was highly reproducible, probably due to only minor manual corrections.…”

Association of G20210A Prothrombin Gene Mutation and Cerebral Ischemic Stroke in Young Patients

“…Although ischemic stroke is not common in the young population, 10-15% of all ischemic stroke events occur in patients 18-50 years of age [ 6 ]. Globally, the annual incidence of ischemic stroke is 1.3 million in adults <50 years of age [ 7 ]. Recent studies have suggested that ischemic stroke in younger patients increases along with an increase in traditional risk factors commonly associated with stroke in older adults [ 6 ].…”