Stroke in Young Adults: Dissection, Venous Sinus Thrombosis & PFO
When a stroke strikes before 50, the cause is rarely plaque
Approach to Stroke Before 50
A different differential. Atherosclerosis and atrial fibrillation dominate stroke in older adults, but in patients under about 50 the list shifts: cervical artery dissection, cardioembolism including paradoxical embolism through a patent foramen ovale (PFO), cerebral venous sinus thrombosis (CVST), stimulant drugs, antiphospholipid syndrome (APS), sickle cell disease, infective endocarditis, reversible cerebral vasoconstriction syndrome (RCVS), and moyamoya.
- Brain MRI with vessel imagingCTA or MRA of the head and neck for dissection, vasculopathy, or venous thrombosis (add MR or CT venography when CVST is possible)
- Cardiac evaluationechocardiography with an agitated-saline bubble study, TEE when needed, and prolonged rhythm monitoring
- Basic tests for young patientsurine drug screen, pregnancy test, blood cultures if febrile, lipids and HbA1c
- Targeted thrombophilia testingantiphospholipid antibodies for arterial events; inherited thrombophilias mainly for venous events
Timing thrombophilia tests. Inherited thrombophilias (factor V Leiden, prothrombin G20210A, and protein C, protein S, and antithrombin deficiency) chiefly matter for venous thrombosis such as CVST or paradoxical embolism. Acute thrombosis and heparin lower antithrombin, and warfarin lowers proteins C and S, so those activity assays are deferred; DNA-based tests are reliable at any time.
Cervical Artery Dissection
Mechanism. An intimal tear allows blood into the arterial wall; the intramural hematoma narrows the lumen and seeds thrombus that embolizes downstream. Triggers include minor trauma, chiropractic manipulation, coughing, and sports, and vascular Ehlers-Danlos syndrome, Marfan syndrome, and fibromuscular dysplasia predispose. Dissection is a leading cause of stroke in young adults.
Presentation. Internal carotid dissection causes ipsilateral neck, face, or head pain with a partial Horner syndrome (ptosis and miosis), pulsatile tinnitus, or lower cranial nerve palsies. Vertebral dissection causes occipital or posterior neck pain with a posterior circulation stroke, classically lateral medullary syndrome. Ischemia may follow the pain by hours to days.
Diagnosis and treatment. CTA or MRA of the head and neck shows a tapered "flame" occlusion, a long narrowed segment (string sign), or an intimal flap; fat-suppressed MRI shows a crescent-shaped intramural hematoma. Duplex ultrasound misses the skull base and much of the vertebral arteries. Treatment is antiplatelet or anticoagulant therapy for 3–6 months (trials show similar efficacy), followed by repeat vessel imaging. Eligible acute strokes still receive IV thrombolysis or thrombectomy. Endarterectomy has no role.
An intracranial dissection presenting with subarachnoid hemorrhage is managed without antithrombotic therapy.
Cerebral Venous Sinus Thrombosis
Presentation. Headache progressing over days (occasionally thunderclap) is the most common symptom, with papilledema, seizures, focal deficits, or encephalopathy. Infarcts are often bilateral or hemorrhagic and cross arterial territories; superior sagittal sinus thrombosis produces bilateral parasagittal lesions, and transverse sinus thrombosis temporal lobe lesions. Risk factors are pregnancy and the postpartum period, estrogen-containing contraceptives, thrombophilia, dehydration, malignancy, nephrotic syndrome, inflammatory bowel disease, and mastoiditis or otitis (transverse and sigmoid sinuses).
Diagnosis. MRI with MR venography, or CT venography, shows the thrombus and absent flow. Noncontrast CT is often normal but may show a hyperdense sinus or cortical vein (dense triangle or cord sign), and contrast CT may show the empty delta sign, a filling defect in the superior sagittal sinus. A normal D-dimer does not exclude CVST.
Treatment. Start therapeutic LMWH or unfractionated heparin immediately, even when venous infarcts have bled: the hemorrhage comes from venous congestion, and stopping clot propagation relieves it. Continue oral anticoagulation (warfarin or a DOAC such as dabigatran) for 3–12 months, longer with a severe thrombophilia. Stop estrogen and treat seizures and raised intracranial pressure. Endovascular therapy or decompressive craniectomy is reserved for deterioration despite anticoagulation.
| Feature | Arterial ischemic stroke | Cerebral venous thrombosis |
|---|---|---|
| Onset | Sudden focal deficit | Headache over days, seizures, papilledema |
| Imaging | Single arterial territory | Bilateral or hemorrhagic lesions crossing territories |
| Key test | CTA or MRA | MR or CT venography |
| Hemorrhage | Halts anticoagulation | Heparin given despite hemorrhage |
Patent Foramen Ovale and Paradoxical Embolism
When to suspect it. About 1 in 4 adults has a PFO. Paradoxical embolism is suspected when a young patient's embolic-appearing stroke has no other cause, begins during a Valsalva maneuver (straining, coughing, lifting), or coincides with DVT or pulmonary embolism: rising right atrial pressure pushes venous clot across the PFO into the systemic circulation.
Evaluation. Agitated-saline echocardiography or transcranial Doppler detects the right-to-left shunt; TEE characterizes the septum (atrial septal aneurysm, shunt size); lower-extremity duplex looks for a venous source. The RoPE score estimates how likely a PFO is causal: younger age, a cortical infarct, and absent vascular risk factors raise it.
Management. Percutaneous closure plus antiplatelet therapy is recommended for patients about 18–60 years old with a nonlacunar, embolic-appearing stroke, no other cause after full evaluation, and a high-risk PFO (atrial septal aneurysm or large shunt). Other patients receive antiplatelet therapy, and anticoagulation is used when DVT or pulmonary embolism is present.
Other Causes
| Cause | Clues | Key management |
|---|---|---|
| Antiphospholipid syndrome | Arterial or venous thrombosis, pregnancy loss, livedo, thrombocytopenia, prolonged aPTT | Warfarin (INR 2–3), not DOACs |
| Cocaine, amphetamines | Onset within hours of use; ischemic stroke, ICH, or SAH | Urine drug screen in every young stroke; abstinence |
| Sickle cell disease | Children with HbSS; large-vessel vasculopathy | Annual TCD ages 2–16; exchange transfusion for acute stroke |
| Infective endocarditis | Fever, new murmur, injection drug use, prosthetic valve | Cultures, echocardiography, antibiotics; no thrombolysis |
| RCVS | Recurrent thunderclap headaches; postpartum or vasoactive drugs | Stop triggers; calcium channel blocker; no glucocorticoids |
| Moyamoya | Hyperventilation-triggered TIAs in children; hemorrhage in adults | Surgical revascularization |
Antiphospholipid syndrome. The diagnosis requires lupus anticoagulant, anticardiolipin, or anti-β2-glycoprotein I antibodies on two occasions at least 12 weeks apart. DOACs allowed more arterial thrombosis than warfarin in trials, especially in triple-positive patients.
Stimulants. Cocaine and amphetamines act through vasospasm, hypertensive surges, accelerated atherosclerosis, and rupture of underlying aneurysms or vascular malformations.
Sickle cell disease. A time-averaged TCD velocity of 200 cm/s or more calls for chronic transfusion keeping HbS below 30%, which prevents most first strokes; after at least a year, hydroxyurea can replace transfusion in selected children without vasculopathy. Acute stroke is treated with urgent exchange transfusion to HbS below 30%, followed by chronic transfusion to prevent recurrence.
Endocarditis. IV alteplase is contraindicated because septic emboli and mycotic aneurysms bleed readily; mechanical thrombectomy can still be considered for a large-vessel occlusion.
RCVS. Several thunderclap headaches over days to weeks follow childbirth, serotonergic or sympathomimetic drugs (SSRIs, triptans, decongestants, cannabis, cocaine), exertion, or orgasm. Angiography shows segmental "string of beads" vasoconstriction that resolves within about 3 months. Convexity SAH, ICH, and ischemic stroke can complicate it. Glucocorticoids, used for CNS vasculitis, worsen outcomes and should be avoided.
Moyamoya. Progressive stenosis of the distal internal carotid and proximal middle and anterior cerebral arteries generates fragile "puff of smoke" collaterals. Associations include East Asian ancestry, sickle cell disease, NF1, Down syndrome, and cranial irradiation. Hyperventilation from crying or blowing lowers PaCO2, constricts vessels, and starves the marginal collateral bed.