Arteriovenous malformations

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

Background: Hemorrhage from cerebral arteriovenous malformations (AVMs) represents 2% of all strokes. It is imperative to have a clear understanding of the diagnostic and treatment algorithms involved with AVM management, because AVMS are a cause of hemorrhage in young adults. The mortality associated with a cerebral arteriovenous malformation is 10% and the morbidity is substantial at 50%.

Pathophysiology: AVMs are congenital lesions composed of a complex tangle of arteries and veins connected by fistulas. The arteries have a deficient muscularis layer. The draining veins are often dilated due to the high velocity of blood flow through the fistulae, and there is no intervening capillary bed. It is unknown how the abnormal vessels appear or exactly when the process begins. Deranged production of vasoactive proteins is under investigation as the angiogenetic link to pathophysiology.

AVMs produce neurologic dysfunction through 3 main mechanisms. First, hemorrhage may occur in the subarachnoid space, the intraventricular space, or most commonly, in the brain parenchyma. Second, in the absence of hemorrhage, seizures may occur as a consequence of AVM: approximately 50% of patients present with seizure disorder. Finally, but rarely, a progressive neurologic deficit, over a few months to several years, may also occur. These slowly progressive neurological deficits are thought to relate to siphoning of blood flow away from adjacent brain tissue (the “steal phenomenon”). Neurologic deficits may be alternatively explained by the mass effect of an enlarging AVM or venous hypertension in the draining veins.

Frequency:

  • In the US: The prevalence of cerebral AVM in the United States is not known. The lifetime detection rate in the general population is approximately 1:100,000.

  • Internationally: The worldwide prevalence is not known. It is usually assumed to be similar to the U.S. worldwide.

Mortality/Morbidity: Although 300,000 persons in the US may harbor AVMs, it is estimated that only 12% of AVMs become symptomatic. Mortality from hemorrhage occurs in 10-15% of cases, and morbidity occurs in approximately 50%.

  • Hemorrhage: the overall risk of intracranial hemorrhage in patients with known AVM is 2-4% per year. Specific angiographic features of the AVM increase the risk of first or subsequent hemorrhage. These include a small-sized venous drainage that is directed deep into the brain, not superficially, and relatively high arterial and venous pressures within the AVM nidus. This last feature can be measured only angiographically, with superselective catheterization. Recurrent hemorrhage occurs in 15-20%, usually within the first year of the bleeding incident. Although the initial presentation of a cerebral hemorrhage may be indistinguishable from other causes of hemorrhage, recovery tends to be better, partly because of the relatively younger age of AVM patients and partly due to functional cerebral reorganization in patients with cerebral AVMs.

  • Seizures: They occur as the presenting symptom in one-quarter to one-half of AVM patients. These may be focal or become secondarily generalized. Satisfactory treatment of seizures is usually possible with standard anticonvulsants.

  • Migraine: Headache occurs in 10-50% of patients with AVM. Refractory headaches may be a presenting symptom if seizures or hemorrhages do not occur. The headache may be typical for migraine or may be present with a less specific complaint of more generalized head pain.

Race: No racial predilection has been identified.

Sex: Both sexes are affected equally.

Age:

  • Despite the presumed congenital origin of AVMs, the clinical presentation most commonly occurs in young adults.

  • AVM hemorrhage or seizure as an incident event may occur in young children or adults over 40; however, childhood migraine is common.

  • A history of subtle learning disorder is elicited in 66% of adults with AVMs. This suggests early effects that are largely subclinical and do not come to medical attention.

Figure 1. Brain arteriovenous malformation. (Click to magnify figure)

CLINICAL PICTURE

History:

  • AVMs tend to be clinically silent until the presenting event occurs. Therefore, the diagnosis is usually made at the time of the first seizure or hemorrhage.

  • A history of minor learning disability is present in up to two-thirds of patients: such dysfunction is rarely apparent in adult life.

  • A history of headaches is present in up to half of the patients with cerebral AVM. It may subsequently take the form of classic migraine or a more generalized headache.

  • If seizures have occurred, a careful seizure history should be obtained. Seizures are simple, partial, or secondarily generalized.

  • The effectiveness of anticonvulsant therapy should be carefully observed and monitored before and during treatment.

Physical:

  • There are rarely physical findings in the absence of hemorrhage in patients with cerebral AVMs.

  • Detailed neuropsychological testing may disclose subtle right or left hemisphere dysfunction.

  • If parenchymal hemorrhage is present, the physical findings are indistinguishable from intracranial hemorrhage due to other causes.

  • Intraventricular hemorrhage generally produces a lesser neurological deficit.

  • In the rare case in which focal neurological deficits are present, the deficit may reflect the location of the AVM.

Causes:

  • No genetic, demographic, or environmental risk factors for cerebral AVM have been clearly identified.

  • Families with cerebral AVMs are rare, and such pedigrees have been too small to enable linkage studies. From the few family cases reported, the inheritance appears to be autosomal dominant.

  • In a small minority of cases, cerebral AVMs are associated with other inherited disorders, such as the Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia), Sturge-Weber disease, neurofibromatosis, and von Hippel Lindau disease.

WORK-UP

  • Lab Studies:

  • Transcranial Doppler (TCD) ultrasound may identify the high velocity, low-resistance flow pattern of a feeding artery to a medium-to-large-sized AVM. Although TCD is a relatively low cost, rapid method of screening, MRI must be used for radiographic diagnosis of larger AVMs.

  • Angiogram is required for hemodynamic assessment, which is essential for planning treatment.

Imaging Studies:

  • High-quality imaging studies are the key to the diagnosis of AVMs

  • CT

    • CT scanning easily identifies an intracerebral hemorrhage, raising suspicion of AVM in a younger person or a patient without clear risk factors for hemorrhage

    • Can identify only the large AVMs

  • MRI

    • Essential for initial diagnosis of AVMs

    • AVMs appear as irregular or globoid masses anywhere within the hemispheres or brainstem

    • May be cortical, subcortical, or in deep gray or white matter

    • Small, round, low-signal spots within or around the mass on T1, T2, or fluid-attenuated inversion recovery (FLAIR) sequences are the “flow voids” of feeding arteries, intranidal aneurysms, or draining veins

    • If hemorrhage has occurred, the mass of blood may obscure other diagnostic features, requiring angiogram or follow-up MRI

    • Low signal of extracellular hemosiderin may be seen around or within the AVM mass, indicating prior symptomatic or asymptomatic hemorrhage

    • Larger aneurysms within the AVM or on feeding arteries may also be occasionally identified

    • Magnetic resonance angiography (MRA) may identify AVMs greater than 1 cm but is inadequate to delineate the morphology of feeding arteries and draining veins; small aneurysms can easily be missed

  • Cerebral angiography

    • Angiography is required in any patient with AVM in whom treatment is being considered

    • The morphology of the AVM determines the treatment algorithm. Important features include feeding arteries, venous drainage pattern, and arterial and venous aneurysms

    • Ten to fifty-eight percent of patients with AVM have aneurysms located in vessels remote from the AVM, in arteries feeding the AVM, or within the nidus of the AVM itself

    • Intranidal aneurysms may have a higher risk of rupture than those outside the bounds of the AVM

    • Other important angiographic features may include kinking or ectasia of draining veins, which can cause venous congestion, thrombosis or rupture, and stenosis of feeding arteries due to angiopathy caused by high velocity, turbulent flow into the fistula

    • Special expertise is required to perform superselective catheterization into AVM feeding arteries for obtaining pressure measurements, as well as to perform superselective anesthetic injections to map neurologic function in and around the AVM (see Superselective angiography )

  • Functional MRI (fMRI)

    • Use of fMRI is becoming more common to map brain function during treatment planning for AVMs.

    • Localization of language, memory, vision, motor, or sensory function may be obtained to help identify “eloquent” brain regions in and around the AVM, prior to treatment by embolization, radiation, or surgery.

Figure 2. Angiogram (A-P view) showing an AVM in the deep left middle cerebral artery (MCA) territory measuring approximately 3 cm in diameter, with a deep draining vein (arrow)., Axial T2 MRI showing an AVM in the left PCA territory with hemorrhage., T1 axial MRI showing a small subcortical AVM in the right frontal lobe. (Click to magnify figure)

Figure 3. T2 coronal MRI showing an AVM in the left medial temporal lobe., Left medial temporal AVM on MRA (Click to magnify figure)

 Procedures:

  • Superselective angiography

    • Superselective angiography is performed with standard cerebral angiography, with access via a femoral artery puncture.

    • A special, flexible, directable catheter is threaded up into one of the main cerebral arteries (carotid or vertebral), then into sequentially smaller branch arteries, until the catheter tip is near or within the AVM nidus.

    • Pressure measurements can be obtained via a coaxial catheter. Higher feeding pressures increase the risk of subsequent hemorrhage.

    • Sodium amytal, an anesthetic agent, can be injected to produce temporary anesthesia of the area perfused by the artery. In this so-called “superselective Wada testing,” language, memory, visual-spatial, sensory, and motor function can be tested during 5 minutes of anesthetic effect to determine whether there is “eloquent” function in that region, which would therefore be at risk for neurologic deficits should that brain area be injured during embolization or surgery. Arteries directly feeding the AVM or “en passage” vessels that feed the AVM but continue past the AVM to feed normal brain tissue can be studied.

MANAGEMENT

Medical Care: Treatment planning for AVMs depends on risk of subsequent hemorrhage, which is determined by the demographic, historical, and angiographic features of the individual patient. Prior hemorrhage, smaller AVM size, deep venous drainage, and relatively high arterial feeding pressures make subsequent hemorrhage more likely. Treatment is recommended for the younger patient with one or more of these high-risk features, whereas an older individual or a patient with no high-risk features may be best treated by managing the medical aspects of the illness alone. In such a case, anticonvulsants for seizure control and appropriate analgesia for headaches may be the only treatment recommendations necessary.

  • Anticonvulsants

    • Standard anticonvulsant therapy, pursuant to the type of seizure, is generally sufficient to bring seizures under control. In many patients, seizures are well controlled with phenytoin, carbamazepine, valproic acid, or lamotrigine.

  • Headache management

    • Standard analgesia for headache may be used, either nonspecific or migraine specific. Serotonin agonists are not specifically contraindicated, unless focal neurologic symptoms appear as a part of the migraine.

Surgical Care: Surgical treatment of AVMs may include surgical resection, endovascular embolization, and focal beam radiation — alone or in combination.

  • Surgical resection

    • Long the mainstay of definitive treatment, surgical resection is most effective with more easily accessible lesions of smaller size. AVMs may be approached with craniotomy over the cerebral convexity, via the skull base, or via the ventricular system. Arterial feeders and draining veins are isolated and ligated, then the nidus is resected. Arterial aneurysms may be clipped surgically as well. Postsurgical angiography is routinely done to ensure that no residual AVM exists; however, cases of reappearance of AVMs, years after a negative postresection angiogram, have been reported.

  • Endovascular embolization

    • Superselective endovascular treatment includes delivery of thrombosing agents such as quick-acting acrylate glue, thrombus-inducing coils, sclerosing drugs, or small balloons into the AVM nidus. The goal of embolization is to block the high-velocity shunting of blood from the high-pressure arterial system into the venous system. Embolization is more often used as a preamble to surgical or radiosurgical treatment than as a definitive treatment.

    • Serial embolization sessions may whittle the AVM down to a fraction of its original size; the reduced AVM size and the presence of embolic material within the AVM make surgery and radiosurgery safer and more accurate. Embolization may be embarked upon to produce relief of neurologic symptoms caused by a large lesion, even if the goal of treatment is not complete obliteration.

  • Radiosurgery

    • Radiosurgery is an option to treat AVMs that are approximately 3 cm in diameter or less. Proton beam, linear accelerator, or gamma knife methods are used to deliver a high dose of radiation to the AVM, while minimizing the effects to surrounding brain tissue; a single dose is generally given. Proton beam irradiation is sometimes attempted with larger lesions. Radiotherapy is thought to work by inducing thrombosis. This approach is appealing because of its apparent noninvasiveness.

    • MRI often shows high signal in surrounding brain white matter following treatment; actual mass effect from edema can be seen when larger territories are covered. Radiosurgery may take 1-3 years to achieve thrombosis of an AVM, thus the patient remains at risk for hemorrhage from AVM during the treatment period.

Consultations: Treatment of AVMs is best achieved with a multispecialty team comprising a neurologist, neuropsychologist, neurosurgeon, interventional neuroradiologist, and neuroanesthesiologist.

Activity:

  • No particular activity restrictions are placed on patients with AVMs, besides the usual postsurgical care.

  • AVM patients with seizures should follow the same protocols as non-AVM epileptic patients.

FOLLOW-UP

Further Inpatient Care:

  • The algorithm for surgical treatment is highly individual and is based on the angiographic characteristics of the AVM.

  • The most common treatment scenario is one or more endovascular embolization sessions during separate hospitalizations, followed by surgical resection or radiosurgery.

  • When hemorrhages occur as the presenting event, a longer hospitalization may be required, with supportive care during recovery of the brain hemorrhage.

Further Outpatient Care:

  • Management of seizure and/or headache medications is usually done by the neurologist or referring physician.

  • Follow-up neuropsychological assessments may be helpful if there are subtle cognitive impairments.

  • Patients who have suffered hemorrhage may need inpatient or outpatient rehabilitation similar to other patients with stroke.

Complications:

  • The most dreaded complication of the AVMs’ natural history is intracerebral hemorrhage (see Prognosis below). Treatment decisions are based on the natural history-risk of first or subsequent hemorrhage versus the risk-benefit ratio of treatment.

  • Surgical complications may include persistent neurological deficits associated with hemorrhage and stroke. Surgical outcome risk correlates with score on the Spetzler-Martin scale; higher scores seen with large-sized AVM, deep venous drainage, and location of the AVM in eloquent brain regions increase the surgical risk. Complication rates for surgery have been assessed as 3% for low-risk patients to as high as 20% for those with higher Spetzler-Martin scores.

  • Complications of endovascular embolization include persistent neurologic deficits related to inadvertent embolization of arteries supplying normal brain tissue. Morbidity has been reported to be in the range of 6-13%. No long-term outcome studies are yet available; however, as endovascular techniques continue to improve, complication rates are likely to diminish.

  • Complication of radiosurgery depends on the size and location of AVM. White matter edema and radiation-induced necrosis may occur during the 1-3 year treatment period along with the risk of recurrent hemorrhage from the AVM until thrombosis has been achieved. Seizure frequency may increase in the first days to weeks after radiosurgery. There is a potential for late effects from radiation, such as accelerated atherosclerosis in surrounding blood vessels.

Prognosis:

  • With an overall risk of intracerebral hemorrhage of 2-4% per year, angiographic assessment is recommended to further define prognosis for patients with AVM.

  • Those with superficial, moderate-sized AVMs have a good long-term prognosis and may not have any additional benefit with interventional treatment.

  • Lifetime risk of hemorrhage may be substantial for young AVM patients.

  • Prognosis after AVM hemorrhage is generally better than that after intracerebral hemorrhage from other causes. Better prognosis may be due to the relatively younger age of patients and a greater potential for reorganization of brain function. More accurate prognosis awaits the results of currently active, long-term, population-based outcome studies.

References

  1. Brown RD Jr, Wiebers DO, Torner JC: Frequency of intracranial hemorrhage as a presenting symptom and subtype analysis: a population-based study of intracranial vascular malformations in Olmsted Country, Minnesota. J Neurosurg 1996 Jul; 85(1): 29-32.

  2. Hartmann A, Mast H, Mohr JP: Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous malformation. Stroke 1998 May; 29(5): 931-4.
  3. Hofmeister C, Stapf C, Hartmann A: Demographic, morphological, and clinical characteristics of 1289 patients with brain arteriovenous malformation [In Process Citation]. Stroke 2000 Jun; 31(6): 1307-10.
  4. Lazar RM, Connaire K, Marshall RS: Developmental deficits in adult patients with arteriovenous malformations. Arch Neurol 1999 Jan; 56(1): 103-6.
  5. Mast H, Mohr JP, Osipov A: ‘Steal’ is an unestablished mechanism for the clinical presentation of cerebral arteriovenous malformations. Stroke 1995 Jul; 26(7): 1215-20.
  6. Mast H, Young WL, Koennecke HC: Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet 1997 Oct 11; 350(9084): 1065-8.
  7. Spetzler RF, Martin NA: A proposed grading system for arteriovenous malformations. J Neurosurg 1986 Oct; 65(4): 476-83.
  8. The Arteriovenous Malformation Study Group: Arteriovenous malformations of the brain in adults. N Engl J Med 1999 Jun 10; 340(23): 1812-8.

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