Arteriovenous Malformation: Symptoms, Types, Causes and Treatment

Arteriovenous malformations (AVMs) are complex vascular anomalies that can have a profound impact on health, often presenting unique challenges for diagnosis and management. Understanding the symptoms, types, causes, and treatment options for AVMs is crucial for both patients and healthcare providers. This article offers a detailed overview of what AVMs are, how they manifest, why they occur, and how they are treated—guided by the latest research and best clinical practices.

Symptoms of Arteriovenous Malformation

AVMs are notorious for their unpredictability, sometimes remaining silent for years and at other times presenting with dramatic, life-threatening symptoms. Recognizing the spectrum of symptoms can prompt timely diagnosis and intervention.

Symptom	Manifestation	Severity	Source
Hemorrhage	Sudden severe headache, neurological decline, bleeding at site	High	3 4 8 7
Seizures	Convulsions, loss of consciousness	Moderate	3 4 1
Neurological Deficits	Weakness, numbness, vision or speech disturbances	Variable	2 3 1
Headache	Chronic or sudden, may mimic migraine	Mild–moderate	3 4
Tinnitus/Pulsatile Mass	Whooshing sound, swelling (esp. in scalp/ear AVMs)	Mild–moderate	5 17
Increased Intracranial Pressure	Vomiting, papilledema, altered consciousness	Severe	2 1

Table 1: Key Symptoms

Recognizing AVM Symptoms

AVM symptoms vary widely based on location and size. In the brain, the most feared presentation is intracerebral hemorrhage, which can cause sudden severe headache, loss of consciousness, and even death, especially in young adults 3 4 8. Other neurological symptoms may include seizures, which can range from focal (affecting one part of the body) to generalized convulsions 3 4.

Neurological and Systemic Manifestations

• Focal Neurological Deficits: Symptoms like weakness, numbness, visual disturbances, or speech difficulties often reflect the area of the brain or spinal cord affected by the AVM. For instance, an AVM impacting the motor cortex may cause hemiparesis, while one near speech centers can cause aphasia 2 1.
• Headaches: Chronic or acute headaches are common and may sometimes mimic migraines 3 4.
• Symptoms of Increased Intracranial Pressure: Larger AVMs or those causing venous congestion can lead to symptoms like vomiting, papilledema (swelling of the optic disc), and altered mental status 2 1.

Peripheral and Unusual Presentations

• Tinnitus and Pulsatile Masses: AVMs located in the scalp or external ear may present as a pulsatile mass, swelling, or a whooshing sound (pulsatile tinnitus) 5 17.
• Others: Depending on the drainage pattern and site, AVMs can result in ataxia (unsteady gait), speech disturbances, or even heart failure in severe pediatric cases 2 5.

Types of Arteriovenous Malformation

AVMs are not a single entity but a group of related disorders that vary by location, structure, and flow dynamics. Understanding these distinctions is key to diagnosis and management.

Type	Location	Features	Source
Cerebral AVMs	Brain	Most common; risk of stroke/seizure	3 4 8 7
Dural AVMs	Dura mater (brain/spinal cord)	May cause cranial nerve symptoms, venous hypertension	1 2
Peripheral AVMs	Limbs, face, trunk	Swelling, pain, cosmetic issues	10 20
Scalp/Ear AVMs	Scalp, auricle	Pulsatile mass, bleeding, tinnitus	5 17
Intrarenal AVMs	Kidney	Hematuria, flank pain	9
Syndromic/Genetic AVMs	Multiple sites	Associated with syndromes (e.g., HHT, CM-AVM)	12 13 15

Table 2: AVM Types

Cerebral (Brain) AVMs

These are the most widely recognized AVMs, consisting of a tangled mass of arteries and veins with direct connections (the nidus) bypassing capillaries. They are a significant cause of hemorrhagic stroke and epilepsy in young adults 3 4 8 7. Brain AVMs may be classified by their anatomical features (e.g., supratentorial vs. infratentorial, size, venous drainage pattern) 7.

Dural AVMs

Dural AVMs occur in the layers covering the brain or spinal cord. Their symptoms often arise from venous hypertension or arterial steal phenomena, leading to cranial nerve deficits or symptoms of increased intracranial pressure. Bleeding risk is high, especially when cortical veins are involved 1 2.

Peripheral and Extracranial AVMs

AVMs can also develop in the limbs, trunk, scalp, or external ear. These lesions may cause swelling, pain, skin discoloration, or cosmetic deformity. Scalp and auricular AVMs can lead to pulsatile masses, local bleeding, or secondary tissue changes 5 10 17.

Visceral AVMs

Less commonly, AVMs can occur in organs such as the kidney (intrarenal AVMs), presenting with hematuria or flank pain 9.

Syndromic and Genetic AVMs

Some AVMs occur as part of genetic syndromes, such as hereditary hemorrhagic telangiectasia (HHT) or capillary malformation-AVM (CM-AVM), and may be multifocal or associated with other vascular anomalies 12 13 15.

Causes of Arteriovenous Malformation

The origins of AVMs have long been debated, with recent research shedding new light on genetic and developmental mechanisms.

Cause	Mechanism/Role	Hereditary?	Source
Congenital Defect	Abnormal vasculogenesis/angiogenesis	Sometimes	3 4 6 8
Somatic Mutations	KRAS/BRAF/MAP2K1, acquired post-zygotically	No	11 14 19
Germline Mutations	RASA1, EPHB4, SMAD4, ENG, ALK1	Yes	12 13 15
Trauma	Rarely, can trigger AVM growth	No	17
Unknown	Idiopathic in some peripheral AVMs	No	9 10

Table 3: AVM Causes

Congenital and Developmental Origins

AVMs are primarily considered congenital malformations—abnormalities in blood vessel development that occur during embryogenesis. The classic view holds that a failure in the normal formation of capillary beds leads to direct artery-to-vein connections 3 4 6 8. However, not all AVMs are present or symptomatic at birth; many manifest later in life.

Genetic Mutations and Pathways

• Somatic (Acquired) Mutations: Recent research has identified high rates of somatic activating mutations—particularly in KRAS, BRAF, and MAP2K1 genes—in brain and spinal AVMs. These mutations occur in endothelial cells after conception, leading to abnormal signaling that drives AVM formation 11 14 19. For example, KRAS mutations activate the MAPK–ERK pathway, promoting abnormal vessel growth 11 14.
• Germline (Inherited) Mutations: Some AVMs are linked to inherited mutations:
  • RASA1 (CM-AVM1) and EPHB4 (CM-AVM2) mutations cause multifocal capillary and AVMs, often with skin findings 12 13.
  • Mutations in SMAD4, ENG, and ALK1 are implicated in hereditary hemorrhagic telangiectasia (HHT), predisposing to multiple AVMs 15.

Environmental and Acquired Factors

While trauma is rarely a direct cause, it can sometimes trigger the growth or presentation of an AVM, particularly in the scalp 17. Most peripheral AVMs, however, are idiopathic, meaning their cause is unknown 9 10.

Treatment of Arteriovenous Malformation

Managing AVMs is complex, requiring a tailored, multidisciplinary approach. Treatment goals include preventing hemorrhage, controlling symptoms, and, when possible, obliterating the lesion.

Treatment	Approach/Technique	Suitability	Source
Observation	Watchful waiting	Small, asymptomatic AVMs	8
Embolization	Endovascular occlusion	Pre-surgery, stand-alone in select cases	16 18 20
Microsurgery	Surgical resection	Accessible, well-circumscribed AVMs	4 7 17 20
Radiosurgery	Stereotactic radiation	Deep/inoperable AVMs, adjunct	4 18
Combined/Multimodal	Two or more methods	Complex AVMs	18 20 17
Genetic/Targeted Therapy	MAPK pathway inhibitors	Select cases, clinical trials	19 12 13 14

Table 4: AVM Treatments

Observation and Risk Assessment

Not every AVM requires immediate intervention. Small, asymptomatic AVMs—especially those in high-risk or deep brain areas—may be managed conservatively, with periodic imaging and symptom monitoring. The decision is based on balancing hemorrhage risk against treatment-related complications 8.

Embolization

Endovascular embolization involves threading a catheter through blood vessels to the AVM and injecting materials (e.g., glue, particles, or ethanol) to block abnormal blood flow. Embolization is commonly used:

• As a pre-surgical adjunct to reduce bleeding
• As a primary treatment for select AVMs, especially peripheral or small intracranial lesions However, complete cure rates are variable, and complication rates—especially hemorrhage—can be significant. Thus, embolization is often part of a multimodal treatment plan 16 18 20.

Surgery

Microsurgical resection remains the gold standard for accessible, well-localized AVMs, especially those in non-eloquent (less critical) brain areas or superficial locations such as the scalp. Surgery aims to completely remove the nidus and abnormal vessels, minimizing recurrence 4 7 17 20. Surgical risks include bleeding, neurological deficits, and infection.

Radiosurgery

For deep, inoperable, or small AVMs, stereotactic radiosurgery (focused radiation) can induce gradual vessel closure over months to years. Radiosurgery is often used as an adjunct to other modalities, especially when complete surgical resection is not possible 4 18.

Multimodal Therapy

Most AVMs, especially complex or recurrent ones, require a combination of treatments. Treatment planning is highly individualized, involving neurosurgeons, interventional radiologists, and radiation oncologists 18 20 17.

Genetic and Targeted Therapies

Emerging research has identified potential for targeted therapies, especially in AVMs with identifiable mutations in the MAPK pathway (e.g., KRAS, BRAF, MAP2K1). Case reports have shown that drugs such as trametinib (a MEK inhibitor) can reduce AVM size and symptoms in select patients 19 12 13 14. These therapies are still investigational but represent a promising frontier for personalized medicine.

Conclusion

Arteriovenous malformations are intricate vascular anomalies that require a nuanced, evidence-based approach. Their symptoms, types, causes, and treatments are diverse and evolving with ongoing research. Here’s a summary of the key points:

• Symptoms: AVMs may cause hemorrhage, seizures, headaches, neurological deficits, or be asymptomatic; presentation depends on location and size.
• Types: AVMs are classified by location (cerebral, dural, peripheral, visceral) and association with genetic syndromes.
• Causes: They arise from congenital defects, somatic or germline mutations (notably in KRAS, BRAF, MAP2K1, RASA1, EPHB4), and rarely trauma.
• Treatment: Management includes observation, embolization, surgery, radiosurgery, and, increasingly, genetic/targeted therapies—often in combination, tailored to individual risk and lesion characteristics.

In summary:

• Early recognition and diagnosis are crucial for optimal outcomes.
• Treatment is best delivered by multidisciplinary teams with expertise in vascular anomalies.
• Ongoing research into genetic causes and targeted therapies is opening new horizons for AVM management.

Understanding AVMs empowers patients and clinicians to make informed decisions and paves the way for improved, individualized care.