What investigations are necessary to determine the cause of stroke in young patients?

Investigations for Young Stroke

Young stroke patients require a comprehensive "heart to head" diagnostic approach that extends beyond standard stroke workup to identify unique etiologies such as arterial dissection, patent foramen ovale, thrombophilia, and rare genetic conditions that are uncommon in older adults. 1, 2

Immediate Imaging Studies

Brain Imaging

• Non-contrast head CT should be performed immediately to exclude hemorrhagic stroke 1
• Brain MRI should follow for detailed parenchymal assessment and to detect small infarcts missed on CT 3, 1
• MRI with diffusion-weighted imaging is superior for identifying acute ischemic changes 1

Vascular Imaging

• CTA or MRA from aortic arch to vertex should be obtained to assess both extracranial and intracranial vasculature 3, 1
• Fat-saturated T1 imaging of the neck is essential to detect extracranial arterial dissections, a leading cause of stroke in young adults 1, 4
• MR venography (MRV) should be included in both hemorrhagic and ischemic presentations, as 10% of hemorrhages in young patients are secondary to cerebral venous sinus thrombosis 1
• Conventional angiography should be considered when MRA is negative but clinical suspicion for dissection remains high, particularly for posterior circulation 1

Cardiac Evaluation

Echocardiography

• Transthoracic echocardiogram with bubble study (agitated saline contrast) should be performed to detect patent foramen ovale and right-to-left shunts, which account for 12-15% of young strokes 3, 1, 4
• Transesophageal echocardiography should be considered for patients with suspected cardioembolic stroke and normal neurovascular imaging, particularly relevant in younger adults with unexplained stroke 3, 1

Cardiac Rhythm Monitoring

• 12-lead ECG should be obtained immediately to identify atrial fibrillation or structural heart disease 3
• Continuous telemetry monitoring during hospitalization is essential 1, 2
• Prolonged ECG monitoring for at least 2 weeks (up to 30 days) should be performed in patients aged ≥55 years with embolic stroke of undetermined source to detect paroxysmal atrial fibrillation 3, 1

Laboratory Investigations

Routine Blood Work

• Complete blood count with platelet count 3
• Coagulation studies: PT/INR, aPTT 3
• Electrolytes and renal function (creatinine, eGFR) 3
• Random glucose or hemoglobin A1c 3
• Lipid profile (fasting or non-fasting) 3, 2
• Troponin to assess for concurrent myocardial ischemia 3
• ESR and CRP for inflammatory conditions 2
• TSH for thyroid dysfunction 2

Specialized Testing for Young Patients

• Antiphospholipid antibody panel (anticardiolipin antibodies, lupus anticoagulant, anti-β2-glycoprotein I) 1
• Protein C, protein S, and antithrombin III levels to evaluate for thrombophilia 1
• Homocysteine level, as hyperhomocysteinemia increases stroke risk by 59% for every 5 μmol/L increase 1
• Sickle cell screen in appropriate populations 3, 2
• RPR/VDRL for syphilis 3, 2
• HIV testing 2
• Toxicology screen and blood alcohol level, as drug abuse is increasingly important in young stroke 5, 2
• Pregnancy test in women of childbearing age 3, 2

Additional Investigations Based on Clinical Suspicion

Infectious/Inflammatory Workup

• Blood cultures if endocarditis is suspected 2
• Lumbar puncture if subarachnoid hemorrhage is suspected and CT is negative, or if vasculitis/infection is considered 3, 2
• Autoimmune panel including ANA if vasculitis is suspected 3

Genetic and Metabolic Testing

• Lipoprotein(a) levels, as elevation is associated with recurrent stroke 3
• MTHFR genotyping if hyperhomocysteinemia is present 1
• Genetic testing for connective tissue disorders (Ehlers-Danlos, Marfan syndrome) if clinical features suggest 3, 5
• Mitochondrial cytopathy evaluation (MELAS, MERRF) in selected cases with suggestive features 3, 5
• Fabry disease screening (α-galactosidase-A) in cryptogenic stroke, particularly with family history 3

Key Differences from Older Adult Workup

The major distinction in young stroke evaluation is the emphasis on:

• Arterial dissection imaging (fat-saturated neck MRI) 1, 4
• Patent foramen ovale detection (bubble study) 1, 4
• Thrombophilia screening 1
• Substance abuse evaluation 5, 2
• Genetic and rare metabolic conditions 3, 5

Common Pitfalls to Avoid

• Do not classify stroke as cryptogenic until completing transesophageal echocardiography, as this identifies additional cardiac sources in patients with normal initial workup 4
• Do not miss arterial dissection by relying solely on standard MRA; fat-saturated T1 sequences are essential 1
• Do not overlook cerebral venous sinus thrombosis in hemorrhagic presentations; always obtain MRV 1
• Do not delay investigation waiting for all results; most definite causes (130 of 145 in one series) are identified by initial evaluation 4
• Do not stop at finding one risk factor; young patients often have multiple contributing factors that require identification 3, 4

Progressive Diagnostic Algorithm

Initial evaluation identifies 90% of definite causes and should include brain imaging, vascular imaging, ECG, and routine blood tests 3, 4. Patients without a definite cause after initial evaluation should undergo transesophageal echocardiography, which identifies additional cardiac sources in 18.5% of cases 4. Further specialized testing (thrombophilia, genetic conditions, vasculitis workup) should be guided by clinical features, family history, and initial findings 3, 2.