ARTERIOVENOUS MALFORMATION (AVM)

OVERVIEW

These defects of the circulatory system consist of an abnormal connection between the arterial system (which normally has a higher intravascular pressure) and the lower pressure venous pathways. Arteries carry oxygen-rich blood away from the heart to the body's cells; veins return oxygen-depleted blood to the lungs and heart. Under ordinary circumstances there is a pressure regulatory system that incorporates progressively smaller arterial vessels in order to reduce the arterial blood pressure until it reaches the vein collection system. This pressure regulatory system relies upon a special ultra-small vessel called "capillaries". This capillary network is vital in order to permit the transfer of nutrients and oxygen to the surrounding tissue as well as reducing the intravascular pressure before the blood is transferred to the relatively thin walled veins. An AVM can occur when the intervening capillary system is absent.

There are several potential consequences to the presence of an AVM. Hemorrhage into surrounding tissue is a real threat since the thin walled vein portion of this malformation may be unable to sustain the higher intravascular blood pressure that is directly shunted from the thicker muscular walled arteries. Hemorrhage can be as little as a "leak" or as destructive as an explosive disruption within the tissue that surrounds it. Ischemia (lack of blood born oxygen) is a frequent problem in the absence of the capillary system which is designed to release oxygen and nutrients to these tissues. Ischemia can lead to the death of Brain cells in the region of an AVM. As pressure within the venous system dilates, blood flow is slowed. The surrounding tissue is subjected to localized pressure upon its neurons and fibre tracts from the dilated veins. The "pressure" related injury can add to the localized Brain tissue ischemic damage which then predisposes this area to hemorrhage.

AVMs can form wherever arteries and veins exist in the Brain. Some are formed from blood vessels located in the Dura Mater or in the Pia Mater, the outermost and innermost, respectively, of the three membranes surrounding the brain and spinal cord. (The third membrane, called the arachnoid, lacks blood vessels.)

Dural and Pial AVMs can appear anywhere on the surface of the Brain. Those located on the surface of the Cerebral Hemispheres - the uppermost portions of the Brain-exert pressure on the Cerebral Cortex, the Brain's "gray matter." Depending on their location, these AVMs may damage portions of the Cerebral Cortex involved with thinking, speaking, understanding language, hearing, taste, touch, or initiating and controlling voluntary movements. AVMs located on the Frontal Lobe close to the Optic Nerve or on the Occipital Lobe, the rear portion of the Cerebrum where images are processed, may cause a variety of visual disturbances.

AVMs can also be located deep within the interior of the Brain. These deep AVMs may compromise the functions of three vital structures: the Thalamus (which transmits nerve signals between the spinal cord and upper regions of the brain); the Basal Ganglia (structures that surround the thalamus and coordinate complex movements); and the Hippocampus (another vital structure that plays a major role in memory and emotions).

AVMs can affect other parts of the Brain besides the Cerebral Hemispheres. The back portion of the Brain (Hindbrain) is formed from two major structures: the Cerebellum (which helps to control balance and coordination), and the Brainstem (which serves as the bridge linking the upper portions of the Brain with the Spinal Cord.) These structures work together to control finely coordinated movements, maintain balance, and regulate some functions of internal organs, including those of the heart and lungs. AVM damage to these parts of the Hindbrain can result in dizziness, giddiness, vomiting, a loss of the ability to coordinate complex movements such as walking, or uncontrollable muscle tremors.

ETIOLOGY (Cause)

There is a normal process both during fetal development, as well as during early human body growth where changes, growth and disappearance of new blood vessels are a continuous process. These changes in the Brain's vascular structure are controlled by angiogenic factors (chemical agents produced by the body that stimulate new blood vessel formation and growth.)

There is one type of Cavernous Malformation involving multiple lesion formation that is caused by a genetic mutation in chromosome 7. Although this genetic mutation appears in many ethnic groups, it is especially frequent in a large population of Hispanic Americans living in the Southwest portion of the USA all of whom share a common ancestor in whom the genetic change occurred.

Additionally there are some other hereditary types of vascular defects of the Central Nervous System (CNS) that are part of larger medical syndromes. AVMs may present as part of a Neurocutaneous Syndrome, such as Osler-Weber-Rendu disease (hereditary hemorrhagic telangiectasia) and Sturge-Weber syndrome. Other genetic diseases associated with AVMs include: Klippel-Trenaunay syndrome, Parkes-Weber syndrome, and Wyburn-Mason syndrome. Rare case reports describe multiple intracranial AVMs and/or concomitant intracranial and intraspinal AVMs. These instances are too rare to be well characterized.

Relationship between AVM & Aneurysm

SYMPTOMS

These abnormalities cause symptoms that vary greatly in severity for about 12 percent of the affected population (about 36,000 of the estimated 300,000 Americans with AVMs). The related symptoms are severe enough to become debilitating or even life-threatening for only a small percentage of the individuals within this group. There is a calculated mortality rate of about 1 percent per year as a direct result of the AVM.

AVM associated symptoms can appear at any age although they are most often noticed when people are in their twenties, thirties, or forties since these abnormalities tend to result from a slow buildup of neurological damage over time. In patients where the AVMs do not become symptomatic by the time people reach their late forties or early fifties, they are highly unlikely to produce symptoms. During pregnancy, however, where there are increases in blood volume and blood pressure there may be a sudden onset or worsening of symptoms, due to these cardiovascular changes.

Seizures (epilepsy) and headaches are the most common and generalized symptoms of AVMs, although there is no particular type of seizure or headache pattern. Seizures can be partial or total, involving a loss of control over movement, convulsions, or a change in a person's level of consciousness. The location of the head pain is not specific to the size or location of the AVM. Headache may involve most of the head and can vary greatly in frequency, duration, and intensity. Occasionally the pain is similar to and as severe as in migraines.

Hemorrhage is more likely to be caused by small lesions, while seizures are more likely to be caused by large lesions. There is a 2-3% annual risk of intracranial hemorrhages associated with AVMs and a 10% mortality rate associated with the initial bleed. The mortality rate associated with the second bleed is 13% with the rate increasing to 20% for each subsequent haemorrhage. There is, in addition, a 50% likelihood of new neurological deficit occurring with each bleed. The location and size of each patient's lesion greatly affects their risk of morbidity and mortality. These statistics are generalized for all AVMs.

There is a wide variety of more specific neurological symptoms that vary from person to person, depending upon the location of the AVM as well as the age of the patient. Subtle learning or behavioral disorders during childhood or adolescence may be the consequence of an AVM. These subtleties can occur long before more obvious symptoms become evident. Paralysis or weakness in one part of the body; loss of coordination (ataxia) and balance (dysequilibrium); difficulty walking (gait disturbance); difficulties carrying out tasks that require planning; dizziness (vertigo); visual disturbances (visual field impairment); double vision (diplopia); communication problems involving the use of or understanding language (aphasia or dysphasia); abnormal sensations such as numbness, tingling, or spontaneous pain (paresthesia or dysesthesia); memory deficits; and mental confusion, hallucinations, or dementia are among the many signs and symptoms found in AVM patients.

There is one distinctive peculiarity that patients may notice that indicates the presence of an AVM. The patient (or more likely a suspicious examining physician) may recognize a sound similar to that made by a torrent of water rushing through a narrow pipe. This "whooshing" sound (called a bruit) caused by excessively rapid blood flow through the arteries and veins of an AVM can sometimes be audible to patients, particularly at night when the surrounding environment is quiet. The bruit may compromise hearing, disturb sleep, or cause significant psychological distress.

DIAGNOSIS

The patient may experience the "bruit" referred to above or a physician may hear it on examination. Any of the symptoms referred to previously may lead the patient to a physician who institutes an investigation.

NEUROIMAGING

Figure 1A (Left): Right Carotid Cerebral Angiogram (lateral view) demonstrating a Posterior Frontal Right Cerebral Hemisphere AVM Figure 1B (Right): Right Carotid Cerebral Angiogram (antero-posterior view) demonstrating additional details of the Posterior Frontal Right Cerebral Hemisphere AVM.

CLASSIFICATION

Table1.

Size of AVM1		Eloquence of adjacent brain2		Pattern of venous drainage3
Small (<3 cm)	1	Noneloquent	0	Superficial only	0
Medium (3-6 cm)	2	Eloquent	1	Deep component	1
Large (>6 cm)	3	...		...

1. Measure the largest diameter of the nidus of the lesion on angiography.
2. Eloquent areas include sensorimotor, language, visual, thalamus, hypothalamus, internal capsule, brain stem, cerebellar peduncles, and deep cerebellar nuclei.
3. The lesion is considered to be "superficial" (on the brain's surface) only if all venous drainage is via the cortical drainage system.

TREATMENT

Medical therapy

It is common to use "Steroids" in an attempt to acutely improve the patient's neurological function since steroids can decrease the swelling (edema) that often accompanies an injury to the Brain. There is no place for the long-term use of steroids since they do nothing to treat the underlying pathology of the disorder and have deleterious side effects such as gastric ulceration, elevated blood glucose levels, and suppression of the immune system.

Surgical therapy

The advantage to direct resection of an AVM is that immediate and permanent cure is possible after complete resection by craniotomy. Surgery is generally recommended for grade 1, 2, and 3 lesions, sometimes for grade 4 lesions, and not for grade 5 lesions.

Figure 2A (Left): Operative Photo (same patient as Figures 1A&B). Compare the larger draining vein (Arrow) on the angiogram to this photograph. Figure 2B (Right): Same patient after complete resection of the AVM. Note the change in the dilated arteries and veins in the post-resection picture to the pre-resection one in Figure 2A.

Among the disadvantages to a direct surgical approach are: ischemic stroke, the potential for significant intraoperative bleeding, and damage to adjacent neural tissue. In most AVM cases, the arteries that supply the AVM also supply intact neural tissue. These must not be destroyed while attempting to selectively interrupt the arterial supply to the AVM. There is the additional risk for "perfusion-breakthrough bleeding". This is a dreadful complication resulting in post-operative hemorrhage into the healthy part of the Brain caused by sudden hemodynamic shifts. These "shifts" result from the removal of a large AV malformation which had previously been "shunting" blood rapidly. Once that "shunt" is removed the subsequent increased flow to the previously underperfused Brain can result in this type of haemorrhage.

Figure 3A (Left): Operative Photo. Large partially calcified AVM Left Temporal Lobe in a patient with Intractable Epilepsy. Figure 3B (Right): Post-excision of the partially calcified AVM. This is only a portion of the AVM resected where the deep (medial) surface has been cut to demonstrate the extent of the lesion and variation in size of the AVM vessels. Clinical Note: The patient tolerated the resection well without additional neurological deficit and the seizures were well controlled.

Other treatment options

The primary advantage of this treatment option is the significant reduction of pathologic blood flow through the lesion. Its main use is as adjuvant therapy prior to craniotomy to decrease intraoperative bleeding and technical difficulty. It has also been used to decrease the size of an AVM to make it sufficiently compact for effective targeting by Stereotactic Radiosurgery.

Nevertheless this is also an invasive procedure with risks to ischemia and hemorrhage that are similar to those for open surgery. The most significant risk is for ischemic stroke by occluding a feeding vessel that also supplies normal Brain. Local tissue hemodynamic alterations that occur after embolization can cause rupture of the AVM, resulting in new neurological deficit from hemorrhage into the Brain, similar to the "perfusion-breakthrough bleeding" described above. Endovascular embolization is not normally used by itself, since it rarely achieves complete obliteration of the AVM. Additionally, even when the vessels are successfully occluded, they are likely to recanalize over time.

Radiosurgery (also known as Stereotactic Radiosurgery) is an important method of treatment for some lesions since it is noninvasive and can access all anatomic locations of the Brain. Unfortunately this technique can only treat smaller lesions (<3 cm in diameter) and requires 2 or more years for its full destructive effect. Radiosurgery is believed to "work" by initiating an "inflammatory" response in the pathological blood vessels which ultimately results in their progressive narrowing and ultimate closure. This process is relatively slow and the risk for hemorrhage is not reduced during this lag time. There is the added risk of radiation necrosis (death) of adjacent healthy brain tissue or brain cyst formation.

Combined Therapy

Radiosurgery may be useful as well in instances where small residual disease has been left after an attempted microvascular resection of the AVM. Leaving a portion of AVM may be part of a planned procedure when there is some significant microsurgical technical difficulty or when the AVM involves "eloquent" or vital Brain structures.

Additional Online Information

http://www.avmsupport.org.uk/brain_avms.php

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This page last edited on 2/19