Provide a comprehensive overview of stroke in young adults (≤50 years), covering epidemiology, risk factors, presentation, diagnostic work‑up, acute treatment, secondary prevention, and prognosis.

Stroke in Young Adults: A Comprehensive Overview

Epidemiology and Emerging Trends

Stroke in young adults (defined as those under 45-50 years of age) represents a growing public health crisis, with incidence rates increasing dramatically from 17 per 100,000 in 1993 to 28 per 100,000 in 2015, despite overall declining stroke rates in older populations. 1, 2

• Young adults account for 10-15% of all stroke patients, with hospitalization rates rising particularly among those aged 25-44 years between 1998 and 2007 3, 4
• The mean age of stroke has decreased from 71.2 years (1993-1994) to 69.2 years (2005) due to increased stroke proportion in individuals 20-54 years of age 3
• Young stroke patients have a clearly increased risk of death compared with the general population, with recurrence rates exceeding 10% within 5 years even in those under 50 years 3, 4
• The economic impact is disproportionately large, as victims become disabled before their most productive years 4, 2

Racial and Ethnic Disparities

• Young and middle-aged Black individuals have substantially higher risk of subarachnoid hemorrhage and intracerebral hemorrhage compared to whites of the same age 3
• African Americans show particularly concerning trends with higher stroke rates, necessitating tailored prevention efforts 2

Risk Factors: A Different Profile Than Older Adults

Traditional Modifiable Risk Factors Predominate

Despite the younger age, traditional cardiovascular risk factors—not exotic causes—drive the majority of young strokes, with hypertension (45%), smoking (37%), and hyperlipidemia (35%) being most prevalent. 5

• Hypertension, diabetes mellitus, hypercholesterolemia, and smoking are present either alone or in combination in the majority of young stroke patients 5
• These modifiable risk factors show no significant difference across geographic, climatic, nutritional, lifestyle, or genetic diversity 4
• The increasing prevalence of obesity, diabetes, and hypertension among young adults directly correlates with rising stroke incidence 2

Unique Risk Factors in Young Adults

• Low birth weight (<2500g) more than doubles stroke risk by age 50 (OR 2.16), with mothers typically being poor, malnourished, and socially disadvantaged 3
• Oral contraceptives are used by 25% of young women who experience stroke 5
• Substance abuse rates are increasing among young adults, contributing to higher stroke rates 2
• Pregnancy-related factors contribute to increased stroke risk in young women 3

Etiologic Spectrum: Broader Than in Older Patients

Distribution of Stroke Subtypes

The etiologic distribution in young stroke differs markedly from older patients, with undetermined causes (21-30%) and atherothrombosis (26.5%) being most common, followed by cardioembolism (20%) and nonatherosclerotic vasculopathies (13%). 4, 5

• Ischemic strokes comprise approximately 85% of all strokes in young adults 6
• Intracerebral hemorrhage accounts for approximately 15% of strokes, with macrovascular lesions (vascular malformations, aneurysms, cavernomas) being particularly important in patients under 50 years 6
• Lacunar strokes account for 6%, migraine-related strokes 3.6%, and other determined causes 10% 5

Causes Requiring Special Consideration in Young Adults

The diagnostic workup must specifically evaluate for arterial dissection, vasculitis, patent foramen ovale, sickle cell disease, Moyamoya, hypercoagulable states, carotid web, and fibromuscular dysplasia—conditions rarely seen in older adults. 3, 1

Inherited Thrombophilias

• Factor V Leiden and prothrombin G20210A mutation show weak but statistically significant associations with stroke, particularly in young adults under 55 years (OR 1.33 for Factor V Leiden, OR 1.44 for prothrombin G20210A) 3
• Testing for inherited thrombophilias should be reserved for young patients (<50 years) with cryptogenic stroke after complete evaluation, those with personal history of unprovoked venous thromboembolism, family history of idiopathic thrombosis, or suspected paradoxical embolism 7
• Protein C, protein S, and antithrombin III testing should be deferred for at least 4-6 weeks after acute stroke to avoid false results 7
• If inherited thrombophilia is identified with concurrent deep vein thrombosis, anticoagulation is mandated regardless of stroke mechanism 7

Hyperhomocysteinemia

• Hyperhomocysteinemia (levels >10 μmol/L) is associated with 2-3 fold increased risk of atherosclerotic vascular disease, with stroke risk increasing 59% for every 5 μmol/L increase 8
• Low birth weight babies have OR 2.16 for stroke, MI, or heart disease by age 50, potentially mediated through hyperhomocysteinemia 3
• For patients with hyperhomocysteinemia, daily standard multivitamin with adequate B6 (1.7 mg/d), B12 (2.4 μg/d), and folate (400 μg/d) is reasonable to reduce homocysteine levels, though evidence for stroke reduction remains incompletely established (Class IIa, Level B) 3, 8

Diagnostic Work-Up: Comprehensive Evaluation Required

Essential Initial Investigations

All young stroke patients require brain imaging (CT or MRI), vascular imaging (carotid ultrasound, CTA, or MRA), cardiac evaluation (ECG, echocardiography), and prolonged cardiac monitoring for at least 2 weeks to detect paroxysmal atrial fibrillation. 3, 7

• Despite careful searching, the cause of stroke remains uncertain in approximately 30% of patients 3
• Diagnostic tests not completed during hospitalization should be prioritized immediately upon arrival in the community, especially carotid imaging and cardiac rhythm monitoring 3

Specialized Testing Based on Clinical Suspicion

• Hypercoagulability panel (antiphospholipid antibodies, Factor V Leiden, prothrombin G20210A, protein C/S/antithrombin III) should be considered in young patients (<50 years) with cryptogenic stroke 7
• Antiphospholipid antibodies require confirmation with repeat testing at least 6 weeks apart to meet diagnostic criteria 7
• Plasma homocysteine measurement is more informative than MTHFR genetic testing, as MTHFR homozygosity accounts for only one-third of hyperhomocysteinemia cases 8

Acute Treatment: Same Principles as Older Adults

• The clinical definition of stroke does not differ based on age: acute or sudden onset of focal neurological deficits attributed to vascular injury (infarction or hemorrhage) of the central nervous system 1
• Standard acute stroke protocols apply, including thrombolysis and thrombectomy when indicated within appropriate time windows 6

Secondary Prevention: Etiology-Directed Approach

Antiplatelet and Anticoagulation Strategies

Secondary prevention must be directed toward the specific stroke etiology while aggressively treating all modifiable risk factors, with dual antiplatelet therapy for up to 90 days being reasonable for severe intracranial stenosis. 3

• For atherosclerotic stroke with aortic arch atheroma, high-intensity statin therapy should reduce LDL-C by ≥50% and achieve LDL-C <70 mg/dL 3
• Antiplatelet therapy is reasonable first-line treatment for patients with identified inherited thrombophilias, with warfarin (INR 2.0-3.0) as an alternative 7
• For antiphospholipid syndrome, warfarin with target INR 2.0-3.0 is a reasonable option 7

Aggressive Risk Factor Management

Health care programs targeting prevention and treatment of hypertension, diabetes, hypercholesterolemia, and smoking are essential, as these factors—present alone or in combination—drive the majority of young strokes. 5

• Blood pressure control, lipid-lowering therapy, and antiplatelet therapy constitute intensive medical therapy for secondary prevention 3
• Physical inactivity, obesity, alcohol abuse, and drug abuse represent behaviorally modifiable risk factors requiring lifestyle interventions 3
• Oral contraceptive use should be reassessed in young women with stroke, particularly those with additional risk factors 5

Vitamin Supplementation for Hyperhomocysteinemia

• For hyperhomocysteinemia, combination therapy with vitamins B6, B12, and folic acid reduced stroke risk by 25% (RR 0.75,95% CI 0.59-0.97) in patients with established vascular disease 8
• Folic acid supplementation alone reduced stroke risk by 18% in meta-analysis of primary prevention trials 8
• Never initiate folate supplementation without first ruling out B12 deficiency, as folate can mask hematologic manifestations while allowing irreversible neurological damage to progress 8

Prognosis and Long-Term Outcomes

Functional Recovery and Disability

Approximately 10% of younger adults (<55 years) develop new stroke-related moderate disability by 90 days, with recovery continuing for years through brain remodeling, compensatory strategies, and adaptive equipment. 3

• Motor strength and limb mobility improve rapidly in the first 30 days and reach maximum recovery by approximately 4 months when rehabilitation is provided 3
• Restoration of ability to engage in physical activities extends beyond 4 months due to brain remodeling, adaptation of compensating strategies, restoration of confidence, and use of adaptive equipment 3
• Life-changing indirect effects include depression, loss of income, and social isolation 3

Recurrence Risk

• Overall, approximately 30% of stroke survivors will have recurrent stroke within their lifetimes, 18% of which will be fatal 3
• Young adults (<50 years) have a >10% recurrence rate within 5 years after first-ever ischemic stroke, with atherothrombotic, cardioembolic, or lacunar subtypes having highest risk 3
• Within the first year after stroke, 5% will have myocardial infarction, and 3% per year thereafter 3
• Recurrent strokes have higher mortality rates and are usually associated with increased severity of disability due to reduced resilience of the remaining injured brain 3

Mortality Considerations

• Young stroke patients have a clearly increased risk of death compared with the general population 4
• Median survival after first stroke is strongly age-dependent: 6-7 years for people 60-69 years, 5-6 years for 70-79 years, and 2-3 years for those >80 years 3

Critical Gaps and Future Directions

There is a lack of specific recommendations and guidelines for stroke management in young adults, representing a major gap given the increasing incidence and unique etiologic profile in this population. 4

• Standardized methodology is needed for more precise epidemiologic data 4
• Further research is required to develop age-specific prevention and treatment strategies 4, 2
• Enhanced healthcare access and primordial prevention of risk factors are needed, particularly for vulnerable groups including African Americans 2
• The 45-year age cutoff is not absolute but represents a practical threshold where differential diagnosis must shift to include causes rarely seen in older adults 1