Arteriovenous Malformations

Overview

Arteriovenous malformations (AVMs) are defects in the vascular system, consisting of tangles of abnormal blood vessels (nidus) in which the feeding arteries are directly connected to a venous drainage network without interposition of a capillary bed. Arteries carry oxygen-rich blood away from the heart to the rest of the body’s tissues and cells. Veins return oxygen-depleted blood to the lungs and heart. Capillaries connect the arteries and veins. The presence of an AVM disrupts this vital cyclical process, causing a snarled tangle of arteries and veins that are connected to one another without the presence of any capillaries(19).

An AVM can occur anywhere in the body, but brain and spinal AVMs present substantial risks when they bleed. Because the brain and its blood vessels are formed together during embryological development, abnormal blood-vessel formation is often associated with abnormal brain tissue. Little is known about the etiology of brain AVMs. The cause of brain AVMs is debated, although it is likely multifactorial, with both genetic manipulation and angiogenic stimulation (the physiological process through which new blood vessels form from pre-existing vessels) appearing to play roles during AVM development. Some believe that AVMs develop in utero, while others advocate an angiopathic reaction, following either a cerebral ischemic or hemorrhagic event (sub-types of stroke) as a primary factor in their development (1).

Causes

The cause of brain AVMs is not known and many believe that they are congenital.

Symptoms + Types

Approximately 50% of patients initially present with a bleed; often patients with an AVM experience no symptoms and their AVMs are discovered only incidentally, usually either during an autopsy or during treatment for an unrelated disorder. The proportion of patients diagnosed with unruptured AVMs has almost doubled in the past three decades with improved non-invasive imaging.2 About 12% of people with AVMs experience symptoms varying in severity. AVMs can irritate the surrounding brain tissue and cause seizures or headaches. Any of the following symptoms may occur:

• Seizures, new onset
• Muscle weakness or paralysis
• Loss of coordination
• Difficulties carrying out organizational tasks
• Dizziness
• Headaches
• Visual disturbances
• Language problems
• Abnormal sensations such as numbness, tingling or spontaneous pain
• Memory deficits
• Mental confusion
• Hallucinations
• Dementia

Traditionally, the annual rupture rate of 4% is cited for brain AVMs, based on a study on natural history of symptomatic AVMs; this study also included AVMs that had previously ruptured.3 A recent randomized trial of unruptured brain arteriovenous malformations (ARUBA) reports a low spontaneous rupture rate of 2.2% per year.4 Other recent prospective studies also report lower bleeding rates of about 1% per year for unruptured AVMs.5,6 The bleeding risk increases after the rupture, achieving 6-8% during the first year, and then it drops to the aforementioned initial values.

AVM characteristics associated with a relatively higher risk of hemorrhage/re-hemorrhage include (6, 8):

• When the brain AVM presents with hemorrhage
• When it has a deep venous drainage
• When it is associated with aneurysms or
• When it is in a deep location.

Testing + Diagnosis

AVMs are usually diagnosed through a combination of magnetic resonance imaging (MRI) and angiography. These tests may need to be repeated to analyze a change in the size of the AVM, recent bleeding or the appearance of new lesions. Left untreated, AVMs can enlarge and rupture, causing intracerebral hemorrhage or subarachnoid hemorrhage, resulting in permanent brain damage. Deep bleeding is usually referred to as an intracerebral or intraparenchymal hemorrhage; bleeding within the membranes or on the surface of the brain is known as subdural hemorrhage or subarachnoid hemorrhage.

The damaging effects and the extent of damage in the neurological status of patients from a hemorrhage are related to lesion location. Bleeding from AVMs located deep inside the interior tissues, or parenchyma of the brain, generally causes more severe neurological damage than does bleeding from lesions located in the dural or pial membranes or on the surface of the brain or spinal cord. AVM location is an important factor to consider when weighing the relative risks of surgical versus nonsurgical treatment. Preventing the rupture or re-rupture of vascular malformations is one of the major reasons that early neurosurgical treatment is recommended for AVMs.

The Spetzler-Martin Grade (SMG) scale is commonly used as a grading scale to predict the risk of surgical morbidity and mortality with brain AVMs. It is a composite score of nidus size, eloquence of adjacent brain (1 point if located in brainstem, thalamus, hypothalamus, cerebellar peduncles or sensorimotor, language, or primary visual cortex) and presence of deep venous drainage (1 point if any or all drainage is through deep veins, such as internal cerebral veins, basal veins or precentral cerebellar veins). The higher the score, the higher is the surgical morbidity and mortality risk.

Treatment + Care

If sudden symptoms, such as severe headache, seizure, weakness in arms or legs, vision problems, balance problems, memory and attention problems are experienced, seek medical attention immediately. If a brain AVM is found, the patient should be referred to a neurosurgeon.

The goal of brain AVM treatment is typically the prevention of new or recurrent hemorrhage from rupture. However, seizure control or stabilization of progressive neurological deficits are occasionally treatment goals. Interventional treatment of ruptured brain AVMs is generally advisable, considering a higher subsequent hemorrhage risk (4.5 to 34%percent) than previously un-ruptured ones (0.9 to 8 percent) (10).

The management options for brain AVMs (ruptured or un-ruptured) include observation or various treatment techniques, such as microsurgical techniques, endovascular embolization and stereotactic radiotherapy used alone or in combination with varying degrees of treatment-associated morbidity and mortality. A treatment plan is devised to offer the lowest risk, yet highest chance of obliterating the lesion.

Although microsurgical treatment affords the opportunity for immediate removal of the AVM, some AVMs may be best dealt with using a multi-modality treatment. In some patients, the AVM is monitored on a regular basis with the understanding that there may be some risk of hemorrhage or other neurological symptoms including seizures or focal deficit. In the most recent study (ARUBA) on 223 patients with unruptured brain AVMs, the risk of death or stroke was significantly lower in the medical management group (the patients were symptomatically treated in the medical management group) than in the interventional therapy group, after a mean follow-up of about 33 months (4). It is a prospective, multicentre, parallel design, non-blinded, randomized controlled trial in which the patients were enrolled from 39 active clinical sites in nine different countries (4).

Resources

In the first randomized trial of unruptured AVMs, ARUBA, medically managed patients had a significantly lower risk of death or stroke and had better outcomes than those treated with intervention at follow-up of 33 months. However, the trial has been controversial because of significant limitations inherent to the study design. The follow-up was too short to demonstrate the benefits of AVM treatment, which is well-understood to be protective over a lifetime. Like other major stroke trials, there was a big gap between the screened and the enrolled patients, suggesting selection bias.11 Some studies showed that results in ARUBA-eligible patients managed outside that trial led to an entirely different conclusion about AVM intervention, due to the primary role of surgery, judicious surgical selection with established outcome predictors and technical expertise developed at high-volume AVM centers.(12)

Sources

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