What are the causes of stroke in young adults (under 45 years)?

Causes of Stroke in Young Adults (Under 45 Years)

Stroke in young adults has distinct etiologies compared to older populations, with arterial dissection, cardiac sources (particularly patent foramen ovale), hypercoagulable states, and substance abuse playing prominent roles, though traditional vascular risk factors remain surprisingly common and should not be overlooked. 1, 2, 3

Primary Causes Unique to Young Adults

Arterial Dissection

• Cervical artery dissections (carotid and vertebral) are relatively common causes of stroke in young patients, occurring either spontaneously or after trivial trauma 1
• Underlying connective tissue disorders increase risk: fibromuscular dysplasia, Marfan syndrome, Ehlers-Danlos syndrome type IV, and osteogenesis imperfecta 1
• Stroke mechanism is predominantly thromboembolic rather than hemodynamic 1
• Dissections can form pseudoaneurysms serving as thrombus sources 1

Cardiac Sources

• Cardioembolic stroke accounts for 47% of young adult strokes, with isolated patent foramen ovale (PFO) representing 17% of cases 4
• Cardiac causes show the strongest association with young stroke (OR: 8.42,95% CI: 3.01-23.5) 5
• High-risk embolic sources more prevalent in young adults include: arterial myxoma, dilated cardiomyopathy, and intracardiac thrombus 6
• Medium-risk sources include: atrial septal defect, nonbacterial thrombotic endocarditis, PFO, and left ventricular hypokinesis 6
• The prothrombin G20210A mutation (but not Factor V Leiden) is significantly more common in young stroke patients with PFO, suggesting susceptibility to paradoxical embolism 1

Hypercoagulable States

• Inherited thrombophilias rarely contribute to adult stroke but play a larger role in young adults, particularly those under 45 years 7, 1
• Prothrombotic mutations show stronger associations in younger populations (<55 years): 1
  • Factor V Leiden (OR: 1.33,95% CI: 1.12-1.58)
  • Prothrombin G20210A (OR: 1.44,95% CI: 1.11-1.86)
  • MTHFR C677T (OR: 1.24,95% CI: 1.08-1.42)
• Specific deficiencies to consider: protein C, protein S, antithrombin III, and elevated factor VIII levels 2
• Antiphospholipid antibodies show strongest association with stroke in young adults (<50 years), with 9.7% of young stroke patients testing positive 1, 7

Uncommon Vascular Causes

• Reversible cerebral vasoconstriction syndrome is more prevalent in young adults than older populations 6
• Moyamoya disease represents a significant cause of stroke and disability in young adults, though rare 8
• Cerebral venous thrombosis occurs more frequently in younger populations 6
• Vasculitis and other vasculopathies should be considered 9

Traditional Risk Factors (Still Important)

Modifiable Vascular Risk Factors

Despite being younger, traditional risk factors remain highly prevalent and often undertreated: 5, 4

• Hypertension is the most significant risk factor across all age groups (OR: 5.41 for ischemic stroke, OR: 9.08 for ICH) 5

  • The population attributable risk for hypertension increases with age even within young adults: 23.3% in those <35 years vs. 50.7% in 35-45 years 5
  • Present in 20% of young stroke patients 4

• Dyslipidemia affects 38% of young stroke patients, with ApoB/ApoA1 ratio showing OR: 2.74 (95% CI: 1.69-4.46) 5, 4

• Diabetes mellitus occurs in 11% of young adults with stroke 4

  • Prevalence in young adults >40 years is comparable to non-young adults 6

• Smoking shows OR: 1.85 (95% CI: 1.17-2.94) and affects 34% of young stroke patients 5, 4

• Central obesity (increased waist-to-hip ratio) demonstrates OR: 1.69 (95% CI: 1.04-2.75) 5

Lifestyle and Behavioral Factors

• Binge drinking of alcohol shows particularly strong association (OR: 5.44,95% CI: 1.81-16.4 for ischemic stroke; OR: 4.06 for ICH) 5
• Psychosocial stress demonstrates OR: 2.33 (95% CI: 1.01-5.41) 5
• Illicit drug use is increasingly recognized as a contributor 9
• Lifestyle-related risk factors (smoking, drinking, obesity) are more frequent in young adults than non-young adults 6

Emerging Risk Factors

The rising incidence of stroke in young adults (up to 90-97% increase in some regions since 2000) cannot be fully explained by traditional risk factors alone: 10

• Air pollution exposure 10
• Long working hours 10
• Prior autoimmune diseases 10
• Endometriosis and hormonal factors in women 11
• Oral contraceptive use 9

Stroke Subtype Distribution

As young adults age, the distribution of stroke mechanisms shifts: 6

• Cardioembolism and stroke of other determined etiologies decrease with advancing age within the young adult category
• Large-artery atherosclerosis and small-vessel occlusion increase proportionally with age, even within young adults
• Multiple infarcts are observed in 31% and are more prevalent in individuals younger than 35 years 4

Diagnostic Yield

Modern diagnostic testing can determine stroke etiology in nearly 90% of young adults: 4

• Cerebral angiography shows relevant abnormalities in 67% (136/203 patients) 4
• Cardiac ultrasonography reveals abnormalities in 51% (100/195 patients) 4
• Hypercoagulable panel positive in 16% (30/189 patients) 4
• Holter monitoring has low yield (2/192 patients) 4

Common Arterial Lesion Locations

• Middle cerebral artery: 23% 4
• Internal carotid artery: 13% 4
• Vertebrobasilar arteries: 13% 4

Clinical Pitfalls

• Do not assume young age excludes traditional vascular risk factors—hypertension, diabetes, and dyslipidemia prevalence increases substantially even within the young adult age range 5, 6
• Cryptogenic stroke is increasing in young adults (11% with undetermined etiology despite thorough evaluation), suggesting unidentified emerging risk factors 10, 4
• Testing for protein C, protein S, or antithrombin levels should be deferred or repeated 4-6 weeks after acute stroke, as these levels may be altered acutely 2