Ischemic stroke in a young adult (generally considered age < 60 years), particularly when traditional vascular risk factors are absent, should raise suspicion for an unusual stroke mechanism.
Evaluate for traditional vascular risk factors, but note that arterial dissection, infective endocarditis, drugs of abuse, and thrombophilia are much more common stroke mechanisms in young compared to older patients. Careful inquiry into family history, preceding headache or neck pain, and illicit drug use are essential.
Brain magnetic resonance imaging (MRI) is useful to help determine the distribution and timing of stroke. Multifocal infarcts or infarcts of different ages suggest an embolic or hypercoagulable source. Carotid ultrasound is not adequate to evaluate for arterial dissection, a common stroke mechanism in the young, and thus computed tomography or MR angiography (CTA/MRA) of the head and neck should be performed. Initial laboratory testing should screen for hematologic abnormalities, renal dysfunction, risk for atherosclerosis, and syphilis. Depending on the context, more specific labs may be warranted (see sections F and H).
Carotid or vertebral arterial dissection is a common cause of stroke in the young. Dissection can occur spontaneously or as a consequence of trauma. A connective tissue disorder may predispose to dissection. Dissection carries a relatively low long-term risk of stroke recurrence. Short-term (1–3 months) aspirin plus clopidogrel is commonly used in those with minor stroke, followed by long-term aspirin monotherapy; the latter tends to be preferred in those with larger strokes to minimize the risk of hemorrhagic transformation. Anticoagulation can be considered if there is stroke recurrence despite antiplatelet therapy. Revascularization with stenting is rarely indicated and should be considered only in those with recurrent hemodynamic symptoms or stroke despite medical therapy.
Reversible cerebral vasoconstriction syndrome (RCVS) typically presents with recurrent thunderclap headaches. It is often associated with the use of sympathomimetic vasoconstrictive drugs such as stimulants and decongestants. A thorough history of prescription and over-the-counter medications as well as illicit drug use is essential. Potentially implicated drugs should be stopped. Verapamil may help mitigate vasoconstriction and treat headache.
Moyamoya disease is characterized by progressive bilateral narrowing of the internal carotid artery terminus extending into the anterior and middle cerebral artery accompanied by a network of small collateral vessels (so-called “puff of smoke”). Most often a primary process (moyamoya disease) likely to have a genetic basis, it can also occur secondary to a specific underlying disease (moyamoya syndrome) such as severe atherosclerosis, syphilis, or antiphospholipid antibody syndrome, amongst others. Moyamoya carries a risk of both ischemic and hemorrhagic stroke. In patients with an ischemic stroke, antiplatelet therapy is appropriate. Adequate hydration and avoidance of hypotension is crucial. Surgical procedures to facilitate collateral flow from the external carotid system to the intracranial circulation can be considered in patients with severe vascular compromise, progressive stenosis, and recurrent stroke.
Central nervous system (CNS) vasculitis may be a primary process or a component of a systemic vasculitis. Thorough evaluation of the kidneys, liver, eyes, and skin to identify a systemic process should be performed. Serum markers of inflammation, systemic autoimmune disease, and infection should be tested; erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-double stranded DNA (Anti-dsDNA), anti-Sjögren’s-syndrome-related antigen A and B (SSA/B), cryoglobulins, human immunodeficiency virus (HIV) and rapid plasma reagin (RPR) are commonly evaluated. Cerebrospinal fluid (CSF) should be evaluated for signs of inflammation with tests for specific infectious causes (such as varicella-zoster virus or fungal infections) based on the CSF profile. In the absence of an infectious or systemic process, primary CNS vasculitis should be considered. Brain/meningeal biopsy and rheumatology consultation are indicated in this scenario.
Transthoracic echocardiography (TTE) with bubble study is a reasonable starting point for cardiac imaging. If unrevealing, proceed to transesophageal echocardiography (TEE) with bubble study.
If no mechanism is found despite above evaluation, testing for high-risk thrombophilia should be performed. This may include testing for antiphospholipid antibodies and protein C and S and antithrombin III deficiency depending on the patient’s age and clinical context. Notably, protein C, S, and antithrombin III measurements are unreliable in the setting of acute thrombosis, so should be measured at least 4–6 weeks after a thrombotic event. The factor V Leiden and prothrombin gene mutation tests are commonly performed, but only when the patient is homozygous or both are positive is anticoagulation generally warranted. In the appropriate clinical context, hypercoagulability of malignancy should also be considered.
Prolonged cardiac monitoring for atrial fibrillation is particularly low yield in patients < 40 years old, but can be considered if older, if there is a family history of atrial fibrillation, or in the presence of cardiac disease by history or on echocardiography.
Cardiac thrombus, severe cardiomyopathy, and nonbacterial thrombotic endocarditis should be treated with long-term anticoagulation. Patients with a cardiac mass should be referred to cardiothoracic surgery. Aortic atherosclerosis > 4 mm or with a significant mobile component is generally treated with dual antiplatelet therapy.