Arteriovenous Malformations

AVMs can affect how the spinal cord functions by causing hemorrhage, by reducing blood flow to the spinal cord, or by causing excess pressure in the blood vessels. Spinal AVMs frequently cause attacks of sudden, severe back pain and can also cause sensory disturbances, muscle weakness or paralysis in the parts of the body served by the spinal cord or the damaged nerve fibers. A spinal cord AVM can lead to degeneration of the nerve fibers within the spinal cord below the level of the lesion, causing widespread paralysis in parts of the body controlled by those nerve fibers.

AVMs on the surface of the cerebral hemispheres—the uppermost portions of the brain—exert pressure on the cerebral cortex, the brain’s “gray matter” that is made up mostly by nerve cells. 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 also can form from blood vessels located deep inside the interior of the cerebrum (the main portion of the brain). These 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 surrounding the thalamus, which coordinates complex movements and plays a role in learning and memory; and the hippocampus, which plays a major role in memory.

AVMs can affect other parts of the brain besides the cerebrum. The hindbrain is formed from two major structures: the cerebellum, which is nestled under the rear portion of the cerebrum, and the brain stem, which serves as the bridge linking the upper portions of the brain with the spinal cord. These structures 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.

The cause of vascular anomalies of the central nervous system is not yet well understood. Scientists believe the anomalies most often result from mistakes that occur during embryonic or fetal development. These mistakes may be linked to genetic mutations in some cases. A few types of vascular malformations are known to be hereditary and thus are known to have a genetic basis. Some evidence also suggests that at least some of these lesions are acquired later in life as a result of injury to the central nervous system.

During fetal development, new blood vessels continuously form and then disappear as the human body changes and grows. These changes in the body’s vascular map continue after birth and are controlled by angiogenic factors, chemicals produced by the body that stimulate new blood vessel formation and growth. Researchers have identified changes in the chemical structures of various angiogenic factors in some people who have AVMs or other vascular abnormalities of the central nervous system. However, it is not yet clear how these chemical changes actually cause changes in blood vessel structure.

By studying patterns of occurrence in families, researchers have established that one type of cavernous malformation involving multiple lesion formation is caused by a genetic mutation in chromosome 7. This genetic mutation appears in many ethnic groups, but it is especially frequent in a large population of Hispanic Americans living in the Southwest; these individuals share a common ancestor in whom the genetic change occurred. Some other types of vascular defects of the central nervous system are part of larger medical syndromes known to be hereditary. They include hereditary hemorrhagic telangiectasia, Sturge-Weber syndrome and Klippel-Trenaunay syndrome.

Arteriovenous malformations cannot be prevented, as they are believed to be congenital. However, vascular endothelial growth factor (VEGF) is a protein involved in the formation of new blood vessels during embryonic development and following injury. Excessive expression of VEGF may play a role in the cause and development of brain AVMs. Researchers funded by the National Institute of Neurological Disorders and Stroke (NINDS) are determining the safety and effectiveness of using an adeno-associated virus (which causes a slight immune response and is not known to cause disease) in an animal model to prevent progression of or reverse the production of abnormal blood vessels.

Additionally, studies of cerebral cavernous malformations (CCMs) show that alterations in the function of structural proteins may also give rise to vascular malformations. Currently there is no therapy to prevent the development or progression of CCMs. NINDS-funded scientists have developed an animal model that studies two of the familial genes related to the development of CCMs. Research shows that the protein signaling pathway Rhoa/ROCK, which allows cells to communicate regarding the formation of cell structure, is involved in blood vessel activity/the flow of molecules and cells into and out of blood vessels. These scientists hypothesize that blocking ROCK activity will inhibit CCM development and hemorrhage, and possibly create a therapy for these malformations.

In most cases, people with neurological AVMs experience few, if any, significant symptoms. In some cases, a weakened blood vessel may burst, spilling blood into the brain (hemorrhage) that can cause stroke and brain damage. Most malformations tend to be discovered only incidentally, usually during treatment for an unrelated disorder or at autopsy.

Treatment options depend on your type of AVM, its location, noticeable symptoms and your general health.

Symptoms, which vary greatly in severity, may include:

• Seizures: They can be focal (meaning they involve a small part of the brain) or generalized (widespread), involving convulsions, a loss of control over movement, or a change in your level of consciousness. No particular type of seizure has been identified.
• Headaches: They can vary greatly in frequency, duration and intensity, sometimes becoming as severe as migraines. No specific pattern of headache has been identified.
• Pain: You may have pain on either one side of the head or on both sides. Sometimes, a headache consistently affecting one side of the head may be closely linked to the site of an AVM. Most often, the location of the pain is not specific to the malformation and may encompass most of the head. Back pain in the lower extremities may be caused by a spinal AVM.
• Visual problems: An AVM can cause problems such as a loss of part of the visual field, inability to control eye movement, or swelling of a part of the optic nerve.
• Muscle weakness: You may have muscle weakness or paralysis in one part of your body.
• Problems with speech: A neurological AVM can cause difficulty speaking or understanding language (aphasia).
• Problems with movement: You may notice a loss of coordination (ataxia) that can lead to such problems as gait disturbances (your manner of walking).
• Abnormal sensations: You may feel sensations such as numbness, tingling or spontaneous pain.

AVMs also can cause a wide range of more specific neurological symptoms that vary from person to person, depending primarily upon the location of the AVM. Such symptoms may include:

• Difficulties carrying out tasks that require planning (apraxia)
• Dizziness
• Loss of consciousness
• Memory deficits
• Subtle learning or behavioral disorders during childhood or adolescence
• Confusion, hallucinations or dementia

Symptoms caused by AVMs can appear at any age. Because the abnormalities tend to result from a slow buildup of neurological damage over time, they are most often noticed when people are in their 20s or older. If AVMs do not become symptomatic by the time people reach their late 40s or early 50s, they tend to remain stable and are less likely to produce symptoms. Some pregnant women may experience a sudden onset or worsening of symptoms due to accompanying cardiovascular changes, especially increases in blood volume and blood pressure.

Although most neurological AVMs have very few, if any, significant symptoms, one particularly severe type of AVM causes symptoms to appear at, or very soon after, birth. Called a vein of Galen defect (named after the major blood vessel involved), this lesion is located deep inside the brain. It is frequently associated with hydrocephalus (an accumulation of fluid within certain spaces in the brain, often with visible enlargement of the head), swollen veins visible on the scalp, seizures, failure to thrive and congestive heart failure. Children born with this condition who survive past infancy often remain developmentally impaired.

The greatest potential danger posed by AVMs is hemorrhage. Most episodes of bleeding remain undetected at the time they occur because they are not severe enough to cause significant neurological damage. But massive, even fatal, bleeding episodes do occur.

A few physical characteristics appear to indicate a greater-than-usual likelihood of clinically significant hemorrhage:

• Smaller AVMs have a greater likelihood of bleeding than do larger ones.
• Impaired drainage by unusually narrow or deeply situated veins increases the chances of hemorrhage.
• Pregnancy appears to increase the likelihood of clinically significant hemorrhage, mainly because of increases in blood pressure and blood volume.
• AVMs that have hemorrhaged once are about nine times more likely to bleed again during the first year after the initial hemorrhage than are lesions that have never bled.

Bleeding from AVMs located deep inside the interior tissues of the brain typically causes more severe neurological damage than does hemorrhage by lesions that have formed in the membranes or on the surface of the brain or spinal cord. (Deeply located bleeding is usually referred to as an intracerebral or parenchymal hemorrhage; bleeding within the membranes or on the surface of the brain is known as subdural or subarachnoid hemorrhage.)

One of the more distinctive signs clinicians use to diagnose an AVM is an auditory phenomenon called a bruit—a rhythmic, whooshing sound caused by excessively rapid blood flow through the arteries and veins of an AVM. The sound is similar to that made by a torrent of water rushing through a narrow pipe. A bruit can sometimes become a symptom when it is especially severe. When audible to individuals, the bruit may compromise hearing, disturb sleep or cause significant psychological distress.

An array of imaging technologies can be used to uncover the presence of AVMs:

• Cerebral angiography, also called cerebral arteriography, provides the most accurate pictures of blood vessel structure in brain AVMs. A special water-soluble dye, called a contrast agent, is injected into an artery and highlights the structure of blood vessels so that it can be seen on X-rays.
• CT scans (computed axial tomography) use X-rays to create an image of the head, brain or spinal cord and are especially useful in revealing the presence of hemorrhage. MRI (magnetic resonance imaging) uses magnetic fields and radio waves to create detailed images that can show subtle changes in neurological tissues.
• Magnetic resonance angiography (MRA) can record the pattern and velocity of blood flow through vascular lesions as well as the flow of cerebrospinal fluid throughout the brain and spinal cord.
• Transcranial Doppler ultrasound can diagnose medium-sized to large AVMs and also detect the presence and extent of hemorrhage. It evaluates blood flow through the brain by directing high-frequency sound waves through the skull at particular arteries. The resulting sound wave signals that bounce back from blood cells are interpreted by a computer to make an image of the velocity of blood flow.

Whenever an AVM is detected, the individual should be carefully and consistently monitored for any signs of instability that may indicate an increased risk of hemorrhage.

There are several options for treating AVMs. Although medication can often lessen general symptoms such as headache, back pain and seizures caused by AVMs and other vascular lesions, the definitive treatment for AVMs is either surgery or focused radiation therapy.  Venous malformations and capillary telangiectases rarely require surgery. Cavernous malformations are usually well defined enough for surgical removal, but surgery on these lesions is less common than for AVMs because they do not pose the same risk of hemorrhage.

Because so many variables are involved in treating AVMs, doctors must assess the danger posed to individuals largely on a case-by-case basis. A hemorrhage from an untreated AVM can cause serious neurological deficits or death, leading many clinicians to recommend surgical intervention whenever the physical characteristics of an AVM appear to indicate a greater-than-usual likelihood of significant bleeding and subsequent neurological damage. However, surgery on any part of the central nervous system carries some risk of serious complications or death. There is no easy formula that can allow physicians and individuals to reach a decision on the best course of therapy.

An AVM grading system developed in the mid-1980s can help healthcare professionals estimate the risk of surgery based on the size of the AVM, location in the brain and surrounding tissue involvement, and any leakage.

Three surgical options are used to treat AVMs: conventional surgery, endovascular embolization and radiosurgery. The choice of treatment depends largely on the size and location of an AVM. Endovascular embolization and radiosurgery are less invasive than conventional surgery and offer safer treatment options for some AVMs located deep inside the brain.

• Conventional surgery involves entering the brain or spinal cord and removing the central portion of the AVM, including the fistula, while causing as little damage as possible to surrounding neurological structures. This surgery is most appropriate when an AVM is located in a superficial portion of the brain or spinal cord and is relatively small in size. AVMs located deep inside the brain generally cannot be approached through conventional surgical techniques because there is too great a possibility that functionally important brain tissue will be damaged or destroyed.
• In endovascular embolization the surgeon guides a catheter through the arterial network until the tip reaches the site of the AVM. The surgeon then injects a substance (such as fast-drying glue-like substances, fibered titanium coils and tiny balloons) that will travel through blood vessels and create an artificial blood clot in the center of an AVM. Since embolization usually does not permanently obliterate the AVM, it is usually used as an adjunct to surgery or to radiosurgery to reduce the blood flow through the AVM and make the surgery safer.
• Radiosurgery is an even less invasive therapeutic approach often used to treat small AVMs that haven’t ruptured. A beam of highly focused radiation is aimed directly on the AVM and damages the walls of the blood vessels making up the lesion. Over the course of the next several months, the irradiated vessels gradually degenerate and eventually close, leading to the resolution of the AVM.

Embolization frequently proves incomplete or temporary, although new embolization materials have led to improved results. Radiosurgery often has incomplete results as well, particularly when an AVM is large, and it poses the additional risk of radiation damage to surrounding normal tissues. Even when successful, complete closure of an AVM takes place over the course of many months following radiosurgery. During that period, the risk of hemorrhage is still present. However, both techniques can treat deeply situated AVMs that had previously been inaccessible. And in many individuals, staged embolization followed by conventional surgical removal or by radiosurgery is now performed, resulting in further reductions in death and complication rates.

Over time, some AVMs get progressively larger as the amount of blood flow increases. In most cases, people with neurological AVMs experience few, if any, significant symptoms. In some cases, a weakened blood vessel may burst, spilling blood into the brain (hemorrhage) that can cause stroke and brain damage. It is recommended that patients limit heavy lifting, activities that cause strain, and anything that raises their blood pressure.

To further your understanding of your diagnosis and to contribute to cutting-edge research, consider participating in a clinical trial so clinicians and scientists can learn more about causes, symptoms, treatment and prevention. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat or prevent disease.

All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research, visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for participants at Clinicaltrials.gov.