Stroke in Korean Young Adults Study

All consecutive patients who had their first-ever ischemic stroke symptoms within the previous month will be asked to enroll in the study. Baseline measurements will be assessed in all patients. Patients without language problems or life-threatening conditions will be asked to answer the structured lifestyle questionnaire. Age- and sex-matched controls without a stroke history will be recruited among patients' friends, relatives and the care-givers of other patients, and will be requested to complete the same questionnaire. People who visit hospital for health check-ups may also be included as controls. After the first assessment, all patients will be followed every 3 months during visits to the outpatient department or by telephone. Participants will be asked about recurrence of stroke, occurrence of post-stroke epilepsy, and functional outcomes on the modified Rankin Scale. In the case of patients who have died, information will be obtained from their last practitioner or care-giver.

Sample size and power calculation. The sample sizes were calculated based on the frequency of psychological distress, which is the most interesting potential risk factor for ischemic stroke in the young. According to a previous report comparing psychological distress in ischemic stroke patients and healthy controls,8 the frequency of stress was 50.3% in the ischemic stroke patients and 38.6% in the healthy controls; a difference of 11.7%. To detect such a difference with a power of 90% and alpha of 0.05 with a drop-out rate of 20%, a sample size of at least 470 patients and 470 controls will be needed (PASS 13).

Clinical information. Demographic and clinical information will be collected on admission.The data include age, gender, traditional risk factors for stroke (hypertension, diabetes, hyperlipidemia, smoking and coronary heart disease), medication history (anti-hypertensives, anti-diabetics, anti-platelets and statins) and other comorbidities. Hypertension is defined as previous use of antihypertensive medication, systolic blood pressure ≥140 mmHg or diastolic BP ≥90 mmHg at discharge, diabetes as previous use of antidiabetic medication or fasting blood glucose ≥126 mg/dL, and hyperlipidemia as previous use of lipid-lowering agents, fasting serum total cholesterol ≥240 mg/dL or low-density lipoprotein ≥160 mg/dL. With regard to cigarette smoking, subjects will be classified as current, former, or non-smokers. Number of pack-years will be noted for former and current smokers. History of coronary heart disease is defined as previous angina pectoris, myocardial infarction, or coronary artery bypass grafting. Patients will also be asked about any other comorbid diseases.

Stroke characteristics and laboratory investigations. Data on stroke characteristics will be collected at admission, including symptoms at time of onset and pre-hospital delay. Severity of stroke will be measured on the National Institutes of Health Stroke Scale (NIHSS) by physicians certified by the Clinical Research Center for Stroke in Korea. The course of the disease during admission will be established, including treatments and complications. On discharge, each case of ischemic stroke will be classified according to the TOAST classification. Modified Rankin Scale (mRS) and Barthel index scores will also be obtained at discharge. Laboratory investigations including complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, urinalysis, urine pregnancy test, serum electrolytes, liver function test, renal function tests, chest X-ray and electrocardiogram will be checked in the emergency department. Other specific laboratory investigations such as fasting blood glucose, hemoglobin A1C, lipid panel test, thyroid function test, rheumatologic panel tests, hypercoagulable panel tests, heavy metal tests, homocysteine and α-galactosidase will be checked on the day after admission, following overnight fasting. For the genetic test for CADASIL, investigators will ask for a further informed consent. All patients will undergo cardiac evaluation during the admission period, including 24-hour Holter monitoring, transthoracic echocardiography and transesophageal echocardiography.

Neuroimaging. Brain imaging studies will be interpreted by more than one neuro-radiologist at each center without any knowledge of the clinical information. Standardized magnetic resonance image (MRI) sequences will be recommended to all participating centers. The minimal requirements for brain imaging studies are diffusion-weighted images, FLAIR images, T2-weighted images, and gradient echo images. All participants will undergo additional vascular imaging studies such as CT angiography, MR angiography or digital subtraction angiography. Based on the neuroimaging, ischemic stroke location, size and vascular territories will be noted. The diagnosis and treatment of stroke will follow the standard guidelines of each coordinating center.