What is the appropriate workup and treatment for a young female presenting with a stroke?

Stroke Workup in a Young Female

Young women presenting with stroke require immediate non-contrast CT head within 30 minutes to exclude hemorrhage, followed by comprehensive vascular imaging (CTA or MRA with fat-saturated T1 neck sequences) and cardiac evaluation including transesophageal echocardiography with bubble study, as this population has unique etiologies including arterial dissection, patent foramen ovale, oral contraceptive-related thrombosis, and pregnancy-related complications that demand different diagnostic approaches than older adults. 1, 2, 3

Immediate Emergency Assessment (Door to Imaging <30 Minutes)

• Non-contrast CT head must be completed within 30 minutes to differentiate ischemic (55% in young patients) from hemorrhagic stroke (45% in young patients) 1, 2, 3
• Obtain NIH Stroke Scale (NIHSS) assessment immediately and document exact time of symptom onset or last known normal, as this determines eligibility for thrombolysis (within 4.5 hours) and thrombectomy (within 24 hours) 1, 2
• Complete blood count with platelets, comprehensive metabolic panel, coagulation studies, and troponin should be obtained immediately but never delay imaging 1

Comprehensive Vascular Imaging (First-Line Screening)

• CT angiography from aortic arch to vertex or MR angiography of neck and intracranial vessels to identify arterial dissection (among the most common causes in young adults), vasculopathy, or large vessel occlusion 2, 3, 4
• Fat-saturated T1 imaging of the neck is essential to detect extracranial arterial dissections, which are frequently missed on standard imaging 3
• MR venography (MRV) should be included in both hemorrhagic and ischemic presentations, as 10% of hemorrhages in young patients result from cerebral venous sinus thrombosis 3
• Brain MRI with diffusion-weighted imaging should follow CT for detailed parenchymal assessment and to detect small infarcts missed on CT 2, 3

Comprehensive Cardiac Evaluation (First-Line Screening)

• 12-lead ECG immediately to detect atrial fibrillation and other arrhythmias 1, 3
• Transthoracic echocardiogram with bubble study (agitated saline contrast) is required to detect patent foramen ovale and right-to-left shunts, which are common cardioembolic sources in young patients 2, 3
• Transesophageal echocardiography should be performed for patients with suspected cardioembolic stroke and normal neurovascular imaging, as it provides superior visualization of cardiac sources including atrial appendage thrombi and valvular abnormalities 2, 3
• Continuous cardiac monitoring for at least 24-72 hours to detect paroxysmal atrial fibrillation 1

Specialized Laboratory Investigations for Young Females

Second-Line Screening (Context-Dependent)

• Antiphospholipid antibody panel (anticardiolipin antibodies, lupus anticoagulant, anti-β2-glycoprotein I) to assess for antiphospholipid syndrome, which should be considered especially in young females with recurrent miscarriages 3, 5
• Protein C, Protein S, and antithrombin III levels to evaluate for inherited thrombophilias 3
• Homocysteine level, as hyperhomocysteinemia increases stroke risk by 59% for every 5 μmol/L increase 3
• Hemoglobin electrophoresis to screen for sickle cell disease in relevant populations (African, Mediterranean, Middle Eastern descent) 2, 3
• Lipid panel and hemoglobin A1c or 75g oral glucose tolerance test for diabetes screening 1

Female-Specific Risk Factor Assessment

• Detailed pregnancy and contraceptive history including current or recent oral contraceptive use, as oral contraceptives may be harmful to women with additional stroke risk factors such as cigarette smoking or prior thromboembolic events 6
• Screen for preeclampsia/eclampsia history, as women with history of preeclampsia should be evaluated 6 months to 1 year postpartum and past childbearing age for persistent vascular risk 6
• Assess for migraine with aura, as increased stroke risk occurs in women who also smoke and have aura 6
• Hormone replacement therapy use, as this should not be used for primary or secondary prevention of stroke in postmenopausal women 6

Third-Line Screening (High Clinical Suspicion)

• Lumbar puncture and immunological tests (including SSB antibody studies, ANA, complement levels) if angiitis or autoimmune disorder suspected, particularly in young females with systemic symptoms 5, 7, 8
• HIV and syphilis serologies in absence of clear etiology 7
• Erythrocyte sedimentation rate and C-reactive protein if giant cell arteritis suspected in patients ≥50 years 1
• Conventional angiography and leptomeningeal biopsy in cases of suspected central nervous system vasculitis refractory to diagnosis 7

Acute Treatment Considerations

• Intravenous alteplase within 4.5 hours of symptom onset for eligible patients using the same criteria as older adults 3
• Mechanical thrombectomy for large vessel occlusions within 24 hours of last known well 3
• LMWH or unfractionated heparin may be initiated pending completion of diagnostic evaluation in ischemic stroke, which differs from typical management in older adults 2, 3
• For carotid web (detected in up to 9.5% of patients <65 years with anterior circulation stroke of unknown cause), antiplatelet therapy is recommended first-line, with carotid stenting or CEA considered if refractory to medical management 6

Critical Pitfalls to Avoid

• Never delay imaging beyond 30 minutes or thrombolysis beyond 60 minutes (target ≤30 minutes) for eligible candidates 1
• Never administer aspirin or antithrombotics before brain imaging rules out hemorrhage 1
• Do not overlook arterial dissection by failing to obtain fat-saturated T1 neck imaging, as this is among the most common causes in young adults 3, 4
• Do not miss patent foramen ovale by performing only transthoracic echo without bubble study or transesophageal echo 2, 3
• Do not assume standard elderly stroke etiologies apply to young patients—approximately one-third will have unique causes requiring specialized evaluation 4, 7
• Inadequate long-term follow-up is a major pitfall, as young patients have longer life expectancy and therefore higher lifetime risk of recurrence (10-25%) 2

Specialized Care Requirements

• Young stroke patients with no identifiable cause after initial workup should be referred to comprehensive stroke centers with specialized expertise in evaluating stroke in the young 3
• Multidisciplinary team including neurology, cardiology, hematology, and obstetrics/gynecology (for pregnancy-related complications) should be available 6, 2
• Despite comprehensive workup, approximately one-third of cases will remain unexplained (cryptogenic stroke), but these patients have lower risk of recurrence 4, 7