Table 1.

Key inclusion criteria for patients and controls.

Patients

Inclusion criteria

(1) Age 18–49 at stroke onset

(2) Patient hospitalised due to first-ever imaging-proven cryptogenic ischaemic stroke after complete and timely minimum diagnostic testing

• Acute ischaemic lesion should preferably be demonstrated by DWI MRI

• In rapidly resolving symptoms with negative DWI, initial CTA or MRA showing an arterial occlusion and/or perfusion-CT or perfusion-MRI imaging of the ischaemic lesion is sufficient to evidence acute cerebral ischaemia

• Silent brain infarcts in the qualifying MRI or previous transient ischaemic attacks are allowed

Exclusion criteria

(1) Baseline minimum tests not obtained in the first week following stroke onset, including:

• Brain MRI

• Routine blood tests (blood count, C-reactive protein, fasting glucose, creatinine, activated partial thromboplastin time, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, glycosylated haemoglobin and haemoglobin electrophoresis in individuals of African origin)

(2) Other baseline minimum tests not obtained within the first 2 weeks following stroke onset, including:

• Imaging of cervicocephalic arteries by CTA, MRA or catheter angiography

• Transesophageal and transthoracic echocardiographya

• 24-h Holter monitoring or continuous in-hospital electrocardiography monitoring with automated atrial fibrillation detection for at least 24 h

• Screening for common thrombophilia,b including antiphospholipid antibodies and other coagulopathies; tests include anticardiolipin antibodies, lupus anticoagulant, anti-β2-glycoprotein antibodies, factor V mutation (or aPC resistance ruled out), factor II mutation, homocysteine, antithrombin III, protein C and protein S

(3) Patient otherwise not eligible for the study or adherent for follow-up or has concurrent disease affecting outcome

(4) Informed consent not obtained from the patient or a proxy

Controls

Inclusion criteria

(1) Age 18–49 years

(2) Absence of prior stroke

(3) Informed consent obtained from the participant

Note: DWI: diffusion-weighted imaging; MRI: magnetic resonance imaging; CTA: computed tomography angiography; MRA: magnetic resonance angiography.

^aTransthoracic echocardiography may remain the only cardiac imaging modality in cases with very severe stroke, receptive aphasia or swallowing difficulties.

^bAbnormal findings concerning coagulation shall be retested >12 weeks from initial testing or >4 weeks after cessation of anticoagulation at any later time point.