What is the likely etiology of cerebral arteriovenous malformations (AVMs) in a teenager?

Etiology of Cerebral Arteriovenous Malformations in Teenagers

Cerebral AVMs in teenagers are traditionally considered congenital lesions that develop during embryonic vascular development but remain clinically silent until adolescence, though emerging evidence suggests some may develop postnatally through acquired mechanisms. 1, 2

Primary Etiology: Congenital Origin

The predominant understanding is that AVMs represent congenital vascular malformations that form during fetal development but do not become symptomatic until later in life. 1

• An estimated 20% of all cerebral AVMs are diagnosed during infancy and childhood, with the majority presenting in adolescence or adulthood despite being present from birth. 1, 2
• AVMs can remain clinically silent for decades before becoming symptomatic, explaining why teenagers often present with lesions that were present since birth but undetected. 2, 3
• The delayed presentation does not indicate delayed formation in most cases—rather, it reflects the natural history of these lesions gradually enlarging or reaching a critical threshold for symptoms. 2

Genetic and Hereditary Factors

Hereditary hemorrhagic telangiectasia (HHT) should be strongly considered in any teenager presenting with multiple AVMs, as this represents the most significant genetic association. 4

• HHT is an autosomal dominant disorder accounting for a substantial proportion of patients with multiple cerebral AVMs. 1, 4
• Familial AVMs have been described in families without specific genetic syndromes, suggesting other hereditary factors may play a role. 1
• TNF-α-238 AG genotype and ApoE ε2 carrier status are independent risk factors for hemorrhage in patients with AVMs, though these do not cause AVM formation itself. 4

Emerging Evidence: Postnatal Development

While less common, there is growing evidence that some AVMs may develop postnatally rather than being purely congenital, challenging traditional understanding. 5, 6

• Multiple case reports document de novo AVM formation in children and adolescents who had normal prior imaging, suggesting acquired development in some cases. 5, 6, 7
• One study identified 3 children with delayed de novo appearance of an AVM after intracerebral hemorrhage with initially normal angiography. 5
• The proposed mechanism involves shear stress stimulating growth factor expression by endothelial cells lining an arteriovenous fistula, potentially triggered by injury or other vascular insults. 5
• Trauma has been implicated as a potential trigger, with at least one case reporting AVM formation in cerebral cortex previously affected by severe traumatic brain injury. 8

Clinical Presentation in Teenagers

More than 75% of symptomatic pediatric AVMs present with hemorrhage, making this the most common initial manifestation in the teenage population. 1, 3, 4

• The annual hemorrhage risk for unruptured AVMs is approximately 2-3% per year, with mortality from first hemorrhage ranging 10-30%. 2, 3, 4
• Teenagers typically present similarly to adults, with seizures, intracranial hemorrhage, or focal neurological deficits rather than the high-output cardiac failure seen in symptomatic neonates. 1
• Approximately 80% of AVMs occur in the supratentorial region when they become symptomatic in children and adolescents. 1

Common Pitfalls and Caveats

Do not assume all AVMs are congenital—maintain clinical suspicion for de novo formation, particularly in patients with prior normal imaging or history of head trauma. 5, 6, 8

• The absence of AVM on prior imaging does not definitively exclude future development, as documented cases show new formation years after normal studies. 5, 6, 7
• Multiple AVMs should prompt evaluation for HHT and genetic counseling, as this has significant implications for screening family members and other organ systems. 1, 4
• Unlike aneurysmal subarachnoid hemorrhage, severe vasospasm from AVM-related hemorrhage is distinctly uncommon. 4