Role of inflammation and haemostasis on aetiology and prognosis in young patients with ischaemic stroke: study protocol of the Observational Dutch Young Symptomatic StrokE study-EXTended (ODYSSEY-nEXT) - a multicentre prospective cohort study.

Abstract

The cause of ischaemic stroke at a young age remains unknown in 30% of cases, highlighting the need to identify hidden causes and risk factors in young patients. Transient and chronic risk factors may interact with the inflammatory and haemostatic systems, potentially driving key mechanisms in the pathogenesis. The 'Observational Dutch Young StrokE study-Extended' (ODYSSEY-nEXT) aims to enhance our understanding of these complex interactions through detailed phenotyping of the immune and haemostatic system and explore their relationship with long-term prognosis. The ODYSSEY-nEXT is a multicentre prospective controlled cohort study of patients aged 18-50 years with a first neuroimaging-proven ischaemic stroke or transient ischaemic attack and healthy controls. We aim to include a total of 200 patients and 60 controls between January 2023 and January 2027. Blood samples will be collected within 72 hours after the index event and at 3 months to assess inflammatory and haemostatic markers. In a subgroup of 20 patients, whole blood analysis will be performed to investigate ex vivo immune cell functionality, the capacity of platelets to release granules and thrombin generation. All patients will complete a questionnaire about trigger and risk factors. Advanced intracranial and extracranial vessel wall imaging with MRI will be performed within a week. Long-term prognosis will be monitored through annual questionnaires about recurrent events for ten years. This study was approved by the Medical Ethical Committee region 'Oost-Nederland' (NL77518.091.21) and will adhere to the Declaration of Helsinki and its later amendments. Participants have to provide written informed consent, but in cases where the patient cannot sign due to physical limitations as a result of the stroke, such as paresis, verbal consent is obtained from the patient and a legal representative will be asked to sign the consent form on their behalf. The findings of this study will be disseminated to healthcare professionals and the scientific community through peer-reviewed publications and to participants through accessible formats such as summary reports or newsletters. NCT05853796.