What are the causes and treatment options for a stroke in a young individual?

Stroke in Young Patients: Causes and Treatment

Immediate Management Priority

Young stroke patients require urgent referral to a comprehensive stroke center with specialized expertise, as this approach significantly improves outcomes and reduces mortality compared to standard care. 1, 2

Key Causes of Stroke in Young Individuals

Most Common Etiologies

Arterial dissection is the leading cause of ischemic stroke in young adults, accounting for approximately 7.5% of pediatric strokes and representing an even higher proportion in young adults. 3 The dissection typically occurs in the extracranial internal carotid artery, though intracranial dissections are more common in children. 3

• Sickle cell disease carries an extraordinarily high stroke risk of 285 per 100,000 per year (0.28% annually), compared to 1.29 per 100,000 in the general pediatric population 3
• Cardioembolic sources including patent foramen ovale, atrial fibrillation, and structural heart disease are common causes requiring both transthoracic and transesophageal echocardiography for detection 1, 2
• Moyamoya disease presents with progressive vasculopathy of the intracranial internal carotid artery with characteristic distal collateral vessels 3
• Vasculitis (both primary CNS and systemic) accounts for 0-20% of strokes in patients under 45 years, depending on depth of workup 3
• Migraine with aura increases stroke risk, particularly when combined with oral contraceptives, smoking, or pregnancy 3

Important Prothrombotic Conditions

• Antiphospholipid antibody syndrome, protein C/S deficiency, antithrombin III deficiency, factor V Leiden 2, 4
• Hyperhomocysteinemia (increases stroke risk by 59% for every 5 μmol/L increase) 4
• MTHFR mutations requiring folate and B-vitamin supplementation 3, 4

Genetic and Connective Tissue Disorders

• Ehlers-Danlos syndrome type IV, Marfan syndrome, fibromuscular dysplasia predispose to arterial dissection 3
• CADASIL, MELAS, and other mitochondrial disorders present with migraine-like headaches and stroke 3

Acute Treatment Approach

For Ischemic Stroke

Initiate anticoagulation with low-molecular-weight heparin (LMWH) or unfractionated heparin immediately while completing diagnostic evaluation, which differs from the typical approach in older adults. 2, 4

• LMWH dosing: Enoxaparin 1.0 mg/kg every 12 hours for patients >2 months old 2
• Unfractionated heparin: Loading dose 75 units/kg IV over 10 minutes, then maintenance infusion 20 units/kg/hour for patients >1 year, targeting aPTT 60-85 seconds 2
• Thrombolysis with tenecteplase or alteplase should be administered within 4.5 hours for eligible patients 4, 5
• Mechanical thrombectomy for large vessel occlusions within 24 hours of last known well 4

For Hemorrhagic Stroke

Neurosurgical evaluation is mandatory for patients with significant mass effect, with consideration of decompressive surgery for malignant middle cerebral artery syndrome or cerebellar hemorrhage. 1, 2

• Immediate anticoagulation reversal and blood pressure control to <140/90 mmHg improves outcomes 5
• For cerebral venous sinus thrombosis causing hemorrhage, paradoxically initiate anticoagulation with IV heparin or subcutaneous LMWH even in the presence of hemorrhage, followed by warfarin for 3-6 months 4

Secondary Prevention Based on Etiology

Arterial Dissection

Anticoagulation with warfarin (target INR 2.0-3.0) for 3-6 months is the primary treatment, followed by transition to antiplatelet therapy. 3, 2, 4 Some physicians avoid anticoagulation for intracranial dissections due to subarachnoid hemorrhage risk, favoring antiplatelet agents instead. 3

Sickle Cell Disease

Long-term prophylactic transfusion therapy is the gold standard for secondary stroke prevention in children with sickle cell disease, reducing recurrent stroke risk from approximately 70% to <10%. 3 In situations where transfusion is unavailable, hydroxyurea reduces recurrence risk (hazard ratio 9.4 for those not receiving it), though it is inferior to transfusion. 3

Cardioembolic Sources

Anticoagulation with warfarin (INR 2.0-3.0) or direct oral anticoagulants for atrial fibrillation, structural heart disease, or patent foramen ovale with high-risk features. 2, 4

Arteriopathies and Vasculitis

• Moyamoya disease: Aspirin may be considered after revascularization surgery or in asymptomatic individuals; anticoagulants are generally not recommended due to hemorrhage risk 3
• Primary CNS vasculitis: Corticosteroids plus pulse cyclophosphamide has been used successfully 3
• Giant cell arteritis: High-dose steroids within 24 hours to prevent blindness 3

Migraine-Related Stroke

Discontinue oral contraceptives immediately in young women with migraine and stroke, switching to alternative birth control. 3 Avoid triptans in patients with hemiplegic migraine, basilar migraine, or known vascular risk factors. 3 Consider prophylaxis with amitriptyline, sodium valproate, cyproheptadine, or calcium channel antagonists plus aspirin. 3

General Antiplatelet Therapy

Aspirin 3-5 mg/kg per day for documented arteriopathy, continuing for minimum 3-5 years or longer if cerebral artery stenosis persists on follow-up imaging. 2 Verify varicella vaccination status before starting aspirin to minimize Reye's syndrome risk. 2

Hyperhomocysteinemia Management

Administer folic acid, vitamin B12, and vitamin B6 to normalize homocysteine levels, which may reduce stroke risk by 18-25%. 3, 4 For MTHFR 677TT genotype, 5-methyltetrahydrofolate is preferred over folic acid. 4

Critical Diagnostic Workup

Immediate Imaging

• Non-contrast head CT to exclude hemorrhage, followed by brain MRI with diffusion-weighted imaging 2, 4
• Fat-saturated T1 imaging of the neck is essential to detect arterial dissection, the leading cause in young adults 4
• Vascular imaging with CTA or MRA of neck and intracranial vessels 2, 4
• MR venography in both ischemic and hemorrhagic presentations, as 10% of hemorrhages are from cerebral venous sinus thrombosis 4

Cardiac Evaluation

• Transthoracic echocardiogram with bubble study (agitated saline contrast) to detect patent foramen ovale 2, 4
• Transesophageal echocardiography for suspected cardioembolic stroke with normal neurovascular imaging 4
• Prolonged ECG monitoring for at least 2 weeks to detect paroxysmal atrial fibrillation 4

Laboratory Studies

• Complete hematological profile including PT/INR, complete blood count, metabolic panel 2
• Antiphospholipid antibody panel, protein C, protein S, antithrombin III levels 4
• Homocysteine level measurement 4
• Sickle cell screening in African American, Mediterranean, and Middle Eastern populations 2

Rehabilitation and Long-Term Management

Comprehensive rehabilitation with a multidisciplinary team should begin in the acute phase, including neurologists, physical therapists, occupational therapists, speech therapists, and psychologists. 1, 2

• Dysphagia screening before oral intake to prevent aspiration pneumonia 2, 4
• Early mobilization with shorter, more frequent sessions 4
• Venous thromboembolism prophylaxis with intermittent pneumatic compression or pharmacological prophylaxis 4
• Vocational assessment early in rehabilitation for work, school, or volunteering, with detailed neuropsychological evaluation to assist planning 4

Follow-Up Monitoring

Regular follow-up is critical as recurrent stroke occurs in 10-25% of young stroke patients, with higher lifetime risk due to longer life expectancy. 1, 2, 4 Repeat neuroimaging to confirm vessel recanalization and detect recurrence. 4

Common Pitfalls to Avoid

• Do not delay anticoagulation in arterial dissection while awaiting complete workup; the 12% risk of recurrent stroke/TIA in the first weeks justifies immediate treatment 3
• Do not withhold anticoagulation in cerebral venous sinus thrombosis with hemorrhage; this is one of the few scenarios where anticoagulation is indicated despite bleeding 4
• Do not assume standard adult stroke protocols apply; young patients require specialized evaluation for unique etiologies like dissection, vasculitis, and genetic disorders 1, 2
• Do not overlook the need for transesophageal echocardiography; transthoracic echo alone misses many cardioembolic sources 2, 4
• Do not continue oral contraceptives in young women with migraine and stroke; the combined risk is substantial 3