are arteriovenous malformations (AVMs)?
What are arteriovenous
AVMs of the brain or spinal cord (neurological AVMs) are believed to affect approximately 300,000 Americans. They occur in males and females of all racial or ethnic backgrounds at roughly equal rates.
What are the symptoms?
Seizures and headaches are the most generalized symptoms of AVMs, but no particular type of seizure or headache pattern has been identified. Seizures can be partial or total, involving a loss of control over movement, convulsions, or a change in a person's level of consciousness. Headaches can vary greatly in frequency, duration, and intensity, sometimes becoming as severe as migraines. Sometimes a headache consistently affecting one side of the head may be closely linked to the site of an AVM. More frequently, however, the location of the pain is not specific to the lesion and may encompass most of the head.
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 muscle weakness or paralysis in one part of the body; a loss of coordination (ataxia) that can lead to such problems as gait disturbances; apraxia, or difficulties carrying out tasks that require planning; dizziness; visual disturbances such as a loss of part of the visual field; an inability to control eye movement; papilledema (swelling of a part of the optic nerve known as the optic disk); various problems using or understanding language (aphasia); abnormal sensations such as numbness, tingling, or spontaneous pain (paresthesia or dysesthesia); memory deficits; and mental confusion, hallucinations, or dementia. Researchers have recently uncovered evidence that AVMs may also cause subtle learning or behavioral disorders in some people during their childhood or adolescence, long before more obvious symptoms become evident.
One of the more distinctive signs indicating the presence of an AVM is an auditory phenomenon called a bruit, coined from the French word meaning noise. (A sign is a physical effect observable by a physician, but not by a patient.) Doctors use this term to describe the 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-that is, an effect experienced by a patient-when it is especially severe. When audible to patients, the bruit may compromise hearing, disturb sleep, or cause significant psychological distress.
Symptoms caused by AVMs can appear at any age, but because these abnormalities tend to result from a slow buildup of neurological damage over time they are most often noticed when people are in their twenties, thirties, or forties. If AVMs do not become symptomatic by the time people reach their late forties or early fifties, they tend to remain stable and rarely produce symptoms. In women, pregnancy sometimes causes a sudden onset or worsening of symptoms, due to accompanying cardiovascular changes, especially increases in blood volume and blood pressure.
In contrast to the vast majority of neurological AVMs, one especially severe type causes symptoms to appear at, or very soon after, birth.Called a vein of Galen defect 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.
How do AVMs damage the brain and
AVMs compromise oxygen delivery to the brain or spinal cord by altering normal patterns of blood flow. Arteries and veins are normally interconnected by a series of progressively smaller blood vessels that control and slow the rate of blood flow. Oxygen delivery to surrounding tissues takes place through the thin, porous walls of the smallest of these interconnecting vessels, known as capillaries, where the blood flows most slowly. The arteries and veins that make up AVMs, however, lack this intervening capillary network. Instead, arteries dump blood directly into veins through a passageway called a fistula. The flow rate is uncontrolled and extremely rapid-too rapid to allow oxygen to be dispersed to surrounding tissues. When starved of normal amounts of oxygen, the cells that make up these tissues begin to deteriorate, sometimes dying off completely.
This abnormally rapid rate of blood flow frequently causes blood pressure inside the vessels located in the central portion of an AVM directly adjacent to the fistula-an area doctors refer to as the nidus, from the Latin word for nest-to rise to dangerously high levels. The arteries feeding blood into the AVM often become swollen and distorted; the veins that drain blood away from it often become abnormally constricted (a condition called stenosis). Moreover, the walls of the involved arteries and veins are often abnormally thin and weak. Aneurysms-balloon-like bulges in blood vessel walls that are susceptible to rupture-may develop in association with approximately half of all neurological AVMs due to this structural weakness.
Bleeding can result from this combination of high internal pressure and vessel wall weakness. Such hemorrhages are often microscopic in size, causing limited damage and few significant symptoms. Even many nonsymptomatic AVMs show evidence of past bleeding. But massive hemorrhages can occur if the physical stresses caused by extremely high blood pressure, rapid blood flow rates, and vessel wall weakness are great enough. If a large enough volume of blood escapes from a ruptured AVM into the surrounding brain, the result can be a catastrophic stroke. AVMs account for approximately 2 percent of all hemorrhagic strokes that occur each year.
Even in the absence of bleeding or significant oxygen depletion, large AVMs can damage the brain or spinal cord simply by their presence. They can range in size from a fraction of an inch to more than 2.5 inches in diameter, depending on the number and size of the blood vessels making up the lesion. The larger the lesion, the greater the amount of pressure it exerts on surrounding brain or spinal cord structures. The largest lesions may compress several inches of the spinal cord or distort the shape of an entire hemisphere of the brain. Such massive AVMs can constrict the flow of cerebrospinal fluid-a clear liquid that normally nourishes and protects the brain and spinal cord-by distorting or closing the passageways and open chambers (ventricles) inside the brain that allow this fluid to circulate freely. As cerebrospinal fluid accumulates, hydrocephalus results. This fluid buildup further increases the amount of pressure on fragile neurological structures, adding to the damage caused by the AVM itself.
Where do neurological AVMs tend to
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 also can form from blood vessels located deep inside the interior of the cerebrum. 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 coordinate complex movements; 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 brainstem, 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.
What are the health consequences of
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 also increases the chances of hemorrhage. Pregnancy also appears to increase the likelihood of clinically significant hemorrhage, mainly because of increases in blood pressure and blood volume. Finally, 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.
The damaging effects of a hemorrhage are related to lesion location. Bleeding from AVMs located deep inside the interior tissues, or parenchyma, of the brain typically causes more severe neurological damage than does hemorrhage by lesions that have formed in the dural or pial 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.) Thus, location is an important factor to consider when weighing the relative risks of surgical versus non-surgical treatment of AVMs.
What other types of vascular lesions
affect the central nervous system?
What causes vascular lesions?
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 recently 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 familial occurrence, researchers have established that one type of cavernous malformation involving multiple lesion formation is caused by a genetic mutation in chromosome 7. This geneticmutation 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 (also known as Osler-Weber-Rendu disease), Sturge-Weber syndrome, Klippel-Trenaunay syndrome, Parkes-Weber syndrome, and Wyburn-Mason syndrome.
How are AVMs and other vascular
Two of the most frequently employed noninvasive imaging technologies used to detect AVMs are computed axial tomography (CT) and magnetic resonance imaging (MRI) scans. CT scans use X-rays to create a series of cross-sectional images of the head, brain, or spinal cord and are especially useful in revealing the presence of hemorrhage. MRI imaging, however, offers superior diagnostic information by using magnetic fields to detect subtle changes in neurological tissues. A recently developed application of MRI technology-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. CT, MRI, and MRA can provide three-dimensional representations of AVMs by taking images from multiple angles.
How can AVMs and other vascular
lesions be treated?
The decision to perform surgery on any individual with an AVM requires a careful consideration of possible benefits versus risks. The natural history of an individual AVM is difficult to predict; however, left untreated, they have the potential of causing significant hemorrhage, which may result in serious neurological deficits or death. On the other hand, surgery on any part of the central nervous system carries its own risks as well; AVM surgery is associated with an estimated 8 percent risk of serious complications or death. There is no easy formula that can allow physicians and their patients to reach a decision on the best course of therapy-all therapeutic decisions must be made on a case-by-case basis.
Today, three surgical options exist for the treatment of AVMs: conventional surgery, endovascular embolization, and radiosurgery. The choice of treatment depends largely on the size and location of an AVM.
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.
Endovascular embolization and radiosurgery are less invasive than conventional surgery and offer safer treatment options for some AVMs located deep inside the brain. In endovascular embolization the surgeon guides a catheter though the arterial network until the tip reaches the site of the AVM. The surgeon then introduces a substance that will plug the fistula, correcting the abnormal pattern of blood flow. This process is known as embolization because it causes an embolus (a blood clot) to travel through blood vessels, eventually becoming lodged in a vessel and obstructing blood flow. The materials used to create an artificial blood clot in the center of an AVM include fast-drying biologically inert glues, fibered titanium coils, and tiny balloons. 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. It involves aiming a beam of highly focused radiation directly on the AVM. The high dose of radiation 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 in recent years 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. Moreover, 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 now offer the possibility of treating deeply situated AVMs that had previously been inaccessible. And in many patients, staged embolization followed by conventional surgical removal or by radiosurgery is now performed, resulting in further reductions in mortality and complication rates.
Because so many variables are involved in treating AVMs, doctors must assess the danger posed to individual patients largely on a case-by-case basis. The consequences of hemorrhage are potentially disastrous, 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 resultant neurological damage.
What research is being done?
In partnership with the medical school of Columbia University, the NINDS has established a long-term Arteriovenous Study Group to learn more about the natural course of AVMs in patients and to improve the surgical treatment of these lesions.
Another group of NINDS -sponsored researchers is currently studying large populations of patients with AVMs to formulate criteria that will allow doctors to predict more accurately the risk of hemorrhage in individual patients. Of particular importance is the role that high blood pressure within the lesion plays in the onset of hemorrhage. Other scientists are examining the genetic basis of familial cavernous malformations and other hereditary syndromes that cause neurological vascular lesions, including ataxia telangiectasia.
Other scientists are seeking to refine the techniques now available to treat AVMs. Radiosurgery is a special area of interest because this technology is still in its infancy. An ongoing study is closely examining the precise effects that radiation exposure has on vascular tissue in order to improve the predictability and consistency of treatment results.
Finally, several ongoing studies are devoted to developing new noninvasive neuroimaging technologies to increase the effectiveness and safety of AVM surgery. Some scientists are pioneering the use of MRI to measure amounts of oxygen present in the brain tissue of patients with vascular lesions in order to predict the brain's response to surgical therapies. Others are developing a new micro-imager that may be inserted into catheters to increase the accuracy of angiography. In addition, new types of noninvasive imaging devices are being developed that detect functional brain activity through changes in tissue light emission or reflectance. This technology may prove more sensitive than MRI and other imaging devices currently available, giving surgeons a new tool for improving the efficacy and safety of AVM surgery.
For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:
Information also is available from:
Organization for Rare Disorders (NORD)
Or follow our Resources link for more useful online information.
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