Cerebral AV Malformations

Cerebral AV Malformations

Cerebral arteriovenous malformations (AVMs) are congenital vascular lesions that are characterized by blood flow from high-pressure arterial vessels directly into thin-walled veins without passing through an intervening capillary/venule system

Synonyms

  • Arteriovenous malformations of the brain
  • AVM
  • Brain AVM
  • Cerebral AV malformations

Incidence

  • •Detection rates in large prospective studies range from 1.1 to 1.4 per 100,000 person-yr.
  • •Incidence of hemorrhage, the most common and often most clinically dangerous presentation, is estimated to be 2% to 4% per yr.

Prevalence

Estimated about 1.3 per 100,000

Predominant Sex and Age

  • •There is a slight male preponderance; studies of varying populations show 1.04:1 to 1.2:1 male:female ratio.
  • •Peak age at time of hemorrhage occurrence is about 20 yr, but it can occur in younger and older patients.

Risk Factors

  • •Male sex and presence of HHT are risk factors for AVM.
  • •The risk of hemorrhage is increased with prior hemorrhage, presence of a single draining vein, and diffuse nidus morphology.

Genetics

  • •Cerebral AVMs are sporadic in most cases.
  • •AVMs are present in about 20% of cases of Osler-Weber-Rendu syndrome (also known as hereditary hemorrhagic telangiectasia [HHT]), an autosomal dominant disorder that results in abnormal blood vessel formation in the skin, lungs, liver, brain, and other organs.

Physical Findings & Clinical Presentation

  • •The most common presentation is hemorrhage; symptoms vary based on location and magnitude of hemorrhage.
  • •Patients may present with seizures or neurologic deficits related to mass effect of the AVM nidus.
  • •Headache and pulsatile tinnitus may be present.
  • •In infants, AVM may present as cyanotic heart failure, macrocephaly, or hydrocephalus.
  • •A bruit may be auscultated through the scalp or orbit.
  • •AVMs may also present with associated intracranial aneurysms that occur on distant, unrelated vessels, on a proximal artery that feeds the aneurysm (flow-related aneurysm), or within the AVM nidus itself (intranidal aneurysm). Patients may present with a subarachnoid hemorrhage related to the aneurysm rather than to the AVM.

Etiology

In most cases, AVMs are congenital abnormalities caused by failure of formation of a capillary bed between embryonic arterial and venous vascular plexuses during the first trimester of gestation; however, de novo sporadic AVMs have been reported.

Differential Diagnosis

The differential diagnosis of cerebral AVMs includes other vascular lesions such as cavernous malformations, dural arteriovenous fistulas, and intracranial aneurysms.

Laboratory Tests

  • •CBC and basic metabolic panel (BMP) with renal function panel prior to contrast dye administration with CT angiography/cerebral angiogram.
  • •Prothrombin time/international normalized ratio/partial thromboplastin time (PT/INR/PTT) should be drawn and corrected in the case of bleeding diathesis.

Imaging Studies

  • •In the acute setting, a CT scan of the head to check for hemorrhage and a CT angiogram of the head for characterization of the lesion may be helpful (although calcification may be present and potentially pose as small acute blood).
  • •MRI of the brain delineates the nidus and its relationship to surrounding soft tissue structures better than a CT scan; however, in the setting of an acute hemorrhage these details will be obscured.
  • •Four-vessel cerebral angiogram (arteriogram) is the best study to evaluate AVM. Angiography in multiple projections helps identify the number and location of feeding and draining vessels for treatment planning. High-resolution images of the nidus may also reveal other irregularities such as aneurysms that often arise given the abnormal histology of the vessel walls and the high-pressure blood flow traversing them.
  • The anterior cerebral artery provides primary arterial supply with venous drainage superficially into the superior sagittal sinus.

 Treatment

Pharmacologic management of seizures with antiseizure drugs and of headaches with oral analgesics can provide symptomatic relief.

Nonpharmacologic Therapy

  • •Observation: The advisability of intervention for unruptured AVMs remains controversial. A randomized trial comparing medical management with specific interventions to obliterate AVMs (neurosurgery, embolization, radiotherapy, or a combination) and prospective follow-up data showed that the rates of neurological disability were higher in the intervention group than with conservative treatment in the form of observation. Whereas patients with unruptured asymptomatic brain AVMs should be observed, treatment may be considered to reduce epileptic seizures or neurologic deficits caused by the AVMs.
  • •Nonemergent outpatient setting: Cerebral angiogram provides characterization of the lesion. Based on angiographic characteristics, the Spetzler-Martin AVM grading system may be used to help guide treatment. In general, grade 5 AVMs are considered unresectable; they are not treated because the risks of treatment likely outweigh the risk of hemorrhage. Current tools for the treatment of AVMs include surgical resection,radiosurgery, and endovascular embolization (with liquid glues or embolic agents).
  • •Surgical resection: In low-grade lesions by an experienced neurosurgeon yields a high cure rate (∼95% in published studies). Resection should include removal of all of the nidus of the AVM; failure to remove the complete nidus may increase the risk of recurrence. An increasing Spetzler-Martin grading scale increases risk of neurologic complications. Intraoperative imaging techniques such as indocyanine-green in-field angiography and conventional digital subtraction angiography are used to verify complete resection.
  • •Radiosurgery: Alternative definitive treatment for AVMs. Traditionally employed to treat AVMs in eloquent areas (e.g., brainstem); stereotactic radiosurgery is increasingly used for higher Spetzler-Martin grade AVM. Reported rates of confirmed radiographic obliteration after AVM radiosurgery range from 47% to 90%.
  • •Endovascular embolization involves transarterial superselective blockage of the AVM. It has become an important adjunctive tool. Currently recommended and approved for use before resection, preoperative embolization can reduce arterial flow and pressure within the AVM, assisting in speed and safety of surgical resection. In addition, embolization may often be used to treat intranidal or flow-related aneurysms in coordination with either resection or radiosurgery. Embolization alone in obliterating an AVM is not routinely recommended.
  • •Treatment decisions should take into consideration the morbidity associated with the treatment modality versus the risk of future hemorrhage or neurologic deterioration. Disability stemming from intractable seizures or severe headaches may make invasive definitive treatment a more attractive option.
  • •Acute cerebral hemorrhage: In the case of an acute hemorrhage, airway and breathing must be maintained, with intubation if necessary. Acute neurosurgical intervention for clot evacuation may be warranted. Microsurgical resection of the AVM may or may not be feasible in the acute setting and is controversial.

Disposition

Whether the patient is receiving elective treatment of a known lesion or presenting with an acute hemorrhage, the patient should receive care in a progressive or intensive care unit with experience dealing with cerebrovascular disease. Once the patient is stabilized, appropriate rehabilitation should be arranged.

Referral

  • •Cerebral AVMs should be managed by a qualified neurosurgeon.
  • •Referral to radiation medicine for adjuvant radiosurgery should be made when indicated.
  • •Referral to an interventional radiologist for endovascular treatment may be warranted.
  • •Treatment in a primary stroke center or other specialized center that offers all treatment modalities is recommended.

 Pearls & Considerations

Comments

  • •No two AVMs are exactly the same; individualization of treatment decisions is the mainstay. Additionally, many AVMs could be effectively treated through one of several modalities or a combination thereof. Factors such as patient age, overall health status, radiographic characteristics, route of surgical access, and potential morbidities of each treatment modality are vital variables in consideration for treatment. Unruptured, asymptomatic AVMs should be observed rather than treated.
  • •The annual risk of hemorrhage from a cerebral AVM is approximately 3%. However, depending on the clinical and anatomical features of the malformations, the risk may be as low as 1% or as high as 33%. The risk of bleeding is increased if the patient has had previous episodes of bleeding, if there is a berry aneurysm on an artery feeding the AVM, and if there is a restriction of venous drainage from the AVM. 11Solomon RA, Connolly ES: Arteriovenous malformations of the brain, N Engl J Med 376:1859-1866, 2017.

Vascular Malformations

From Kliegman RM et al: Nelson textbook of pediatrics, ed 19, Philadelphia, 2011, Saunders.

TypeExample(s)
CapillaryPort-wine stain
VenousVenous malformation
Angiokeratoma circumscriptum (hyperkeratotic venule)
Cutis marmorata telangiectasia congenita (congenital phlebectasia)
ArterialArteriovenous malformation
LymphaticSuperficial lymphatic malformation (lymphangioma circumscriptum)
Deep lymphatic malformation with macrocysts and/or microcysts (cystic hygroma)

Major Differences Between Hemangiomas and Vascular Malformations

From Eichenfeld LF et al: Textbook of neonatal dermatology, Philadelphia, 2001, Saunders.

HemangiomasVascular Malformations (Capillary, Venous, Lymphatic, Arterial, and Arteriovenous, Pure, or Complex-Combined)
ClinicalVariably visible at birthUsually visible at birth (AVMs may be quiescent)
Subsequent rapid growthGrowth proportionate to the skin’s growth (or slow progression); present lifelong
Slow, spontaneous involution
Sex ratio F:M3:1-5:1; 7:1 in severe cases1:1
PathologyProliferating stage: Hyperplasia of endothelial cells and smooth muscle cell actin–positive cellsFlat endothelium
Multilaminated basement membraneThin basement membrane
Higher mast cell content in involutionOften irregularly attenuated walls (VM, LM)
RadiologyFast-flow lesion on Doppler sonographySlow-flow (CM, LM, VM) or fast-flow (AVM) on Doppler ultrasonography
Tumoral mass with low voids on MRIMRI: Hyperintense signal on T2-weighted images when slow-flow (LM, VM); flow voids on T1- and T2-weighted images when fast-flow (AVM)
Lobular tumor on arteriogramArteriography of AVM demonstrates AV shunting
Bone changesRarely mass effect with distortion but no invasionSlow-flow VM: Distortion of bones, thinning, underdevelopment
Slow-flow CM: Hypertrophy
Slow-flow LM: Distortion, hypertrophy, and invasion of bones
High-flow AVM: Destruction, rarely extensive lytic lesions
Combined malformations (e.g., slow-flow [capillary lymphatic venous malformation, Klippel-Trenaunay syndrome] or fast-flow [capillary arteriovenous malformation, Parkes Weber syndrome]): Overgrowth of limb bones, gigantism
Immunohistochemistry on tissue samplesProliferating hemangioma: High expression of PCNA, type IV collagenase, VEGF, urokinase, and bFGF, glucose transporter-1Lack expression of PCNA, type IV collagenase, urokinase, VEGF, and bFGFOne familial (rare) form of VM linked to a mutated gene on 9p (VMCM1)
Involuting hemangioma: High levels of tissue inhibitor of metalloproteinase-1, bFGF
HematologyNo coagulopathy (Kasabach-Merritt syndrome is a complication of other vascular tumors of infancy, e.g., kaposiform hemangioendothelioma and tufted angioma)Slow-flow VM, LM, or LVM may have an associated localized intravascular coagulopathy with risk of bleeding (disseminated intravascular coagulation)

AV, Atrioventricular; AVM, arteriovenous malformation; bFGF, basic fibroblast growth factor; CM, capillary malformation/port-wine stain; F:M, female:male; LM, lymphatic malformation; LVM, lymphovenous malformation; MRI, magnetic resonance imaging; PCNA, proliferating cell nuclear antigen; VEGF, vascular endothelial growth factor; VM, venous malformation.

Patient & Family Education

If a patient with a known AVM suffers from acute-onset neurologic deficits or stroke-like symptoms, emergency medical attention is warranted for potential hemorrhage. Presence of AVMs, cerebral or otherwise, in family members should be disclosed to the patient’s primary care physician because the presence of a genetic condition predisposing to cerebral AVMs should be considered.

Sources

  1. Al-Shahi Salman R., et al.: Outcome after conservative management or intervention for unruptured brain arteriovenous malformations. JAMA 2014; 311: pp. 1661-1669.
  2. Mohr J.P., et al.: Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre non-blinded, randomized trial. Lancet 2014; 383: pp. 614-621.
  3. Ruigrok Y.M.: Management of unruptured cerebral aneurysms and arteriovenous malformations. Continuum (Minneap Minn) 2020; 26 (2): pp. 478-498. (Cerebrovascular Disease).
  4. Solomon R.A., Connolly E.S.: Arteriovenous malformations of the brain. N Engl J Med 2017; 376: pp. 1859-1866.
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