Cerebral arteriovenous malformation

The most frequently observed problems, related to an AVM, are headaches and seizures, cranial nerve deficits,[2] backaches, neckaches and eventual nausea, as the coagulated blood makes its way down to be dissolved in the individual's spinal fluid. It is supposed that 15% of the population, at detection, have no symptoms at all.[3] Other common symptoms are a pulsing noise in the head, progressive weakness and numbness and vision changes as well as debilitating, excruciating pain.[4][5]

In serious cases, the blood vessels rupture and there is bleeding within the brain (intracranial hemorrhage). Nevertheless, in more than half of patients with AVM, hemorrhage is the first symptom.[6] Symptoms due to bleeding include loss of consciousness, sudden and severe headache, nausea, vomiting, incontinence, and blurred vision, amongst others.[4] Impairments caused by local brain tissue damage on the bleed site are also possible, including seizure, one-sided weakness (hemiparesis), a loss of touch sensation on one side of the body and deficits in language processing (aphasia).[4] Ruptured AVMs are responsible for considerable mortality and morbidity.[7]

AVMs in certain critical locations may stop the circulation of the cerebrospinal fluid, causing accumulation of the fluid within the skull and giving rise to a clinical condition called hydrocephalus.[5] A stiff neck can occur as the result of increased pressure within the skull and irritation of the meninges.[8]

AVMs are an abnormal connection between the arteries and veins in the human brain. Arteriovenous malformations are most commonly of prenatal origin.[9] In a normal brain oxygen enriched blood from the heart travels in sequence through smaller blood vessels going from arteries, to arterioles and then capillaries.[9] Oxygen is removed in the latter vessel to be used by the brain.[9] After the oxygen is removed blood reaches venules and later veins which will take it back to the heart and lungs.[9] On the other hand, when there is an AVM blood goes directly from arteries to veins through the abnormal vessels disrupting the normal circulation of blood.[9][10]

Axial image from computerized tomography angiogram showing arteriovenous communication in vein of Galen malformation

Vein of Galen thrombosis from ventricular puncture, not to be mistaken for an aneurysmal malformation

An AVM diagnosis is established by neuroimaging studies after a complete neurological and physical examination.[5][11] Three main techniques are used to visualize the brain and search for AVM: computed tomography (CT), magnetic resonance imaging (MRI), and cerebral angiography.[11] A CT scan of the head is usually performed first when the subject is symptomatic. It can suggest the approximate site of the bleed.[3] MRI is more sensitive than CT in the diagnosis of AVMs and provides better information about the exact location of the malformation.[11] More detailed pictures of the tangle of blood vessels that compose an AVM can be obtained by using radioactive agents injected into the blood stream. If a CT is used in conjunctiangiogram, this is called a computerized tomography angiogram; while, if MRI is used it is called magnetic resonance angiogram.[3][11] The best images of an AVM are obtained through cerebral angiography. This procedure involves using a catheter, threaded through an artery up to the head, to deliver a contrast agent into the AVM. As the contrast agent flows through the AVM structure, a sequence of X-ray images are obtained.[11]

Treatment depends on the location and size of the AVM and whether there is bleeding or not.[18]

The treatment in the case of sudden bleeding is focused on restoration of vital function.[19]

Medical management

Anticonvulsant medications such as phenytoin are often used to control seizure; medications or procedures may be employed to relieve intracranial pressure. Eventually, curative treatment may be required to prevent recurrent hemorrhage. However, any type of intervention may also carry a risk of creating a neurological deficit.[20]

Preventive treatment of as yet unruptured brain AVMs has been controversial, as several studies suggested favorable long-term outcome for unruptured AVM patients not undergoing intervention. The NIH-funded longitudinal ARUBA study ("A Randomized trial of Unruptured Brain AVMs) compares the risk of stroke and death in patients with preventive AVM eradication versus those followed without intervention.[21] Interim results suggest that fewer strokes occur as long as patients with unruptured AVM do not undergo intervention. Because of the higher than expected event rate in the interventional arm of the ARUBA study, NIH/NINDS stopped patient enrollment in April 2013, while continuing to follow all participants to determine whether the difference in stroke and death in the two arms changes over time.[22]

Surgical management

Surgical elimination of the blood vessels involved is the preferred curative treatment for many types of AVM.[18] Surgery is performed by a neurosurgeon who temporarily removes part of the skull (craniotomy), separates the AVM from surrounding brain tissue, and resects the abnormal vessels.[18] While surgery can result in an immediate, complete removal of the AVM, risks exist depending on the size and the location of the malformation. The AVM must be resected en bloc, for partial resection will likely cause severe hemorrhage.[7] The preferred treatment of Spetzler-Martin grade 1 and 2 AVMs in young, healthy patients is surgical resection due to the relatively small risk of neurological damage compared to the high lifetime risk of hemorrhage. Grade 3 AVMs may or may not be amenable to surgery. Grade 4 and 5 AVMs are not usually surgically treated.[23]

Radiosurgical management

Radiosurgery has been widely used on small AVMs with considerable success. The Gamma Knife is an apparatus used to precisely apply a controlled radiation dosage to the volume of the brain occupied by the AVM. While this treatment does not require an incision and craniotomy (with their own inherent risks), three or more years may pass before the complete effects are known, during which time patients are at risk of bleeding.[18] Complete obliteration of the AVM may or may not occur after several years, and repeat treatment may be needed. Radiosurgery is itself not without risk. In one large study, nine percent of patients had transient neurological symptoms, including headache, after radiosurgery for AVM. However, most symptoms resolved, and the long-term rate of neurological symptoms was 3.8%.[24]

Neuroendovascular therapy

Embolization is performed by interventional neuroradiologists and the occlusion of blood vessels most commonly is obtained with Ethylene-vinyl alcohol copolymer (Onyx) or N-butyl cyanoacrylate (NBCA). These substances are introduced by a radiographically guided catheter, and block vessels responsible for blood flow into the AVM.[25] Embolization is frequently used as an adjunct to either surgery or radiation treatment.[18] Embolization reduces the size of the AVM and during surgery it reduces the risk of bleeding.[18] However, embolization alone may completely obliterate some AVMs. In high flow intranidal fistulas balloons can also be used to reduce the flow so that embolization can be done safely.[26]

The main risk is intracranial hemorrhage. This risk is difficult to quantify since many patients with asymptomatic AVMs will never come to medical attention. Small AVMs tend to bleed more often than do larger ones, the opposite of cerebral aneurysms.[27] If a rupture or bleeding incident occurs, the blood may penetrate either into the brain tissue (cerebral hemorrhage) or into the subarachnoid space, which is located between the sheaths (meninges) surrounding the brain (subarachnoid hemorrhage). Bleeding may also extend into the ventricular system (intraventricular hemorrhage). Cerebral hemorrhage appears to be most common. [3] One long-term study (mean follow up greater than 20 years) of over 150 symptomatic AVMs (either presenting with bleeding or seizures) found the risk of cerebral hemorrhage to be approximately 4% per year, slightly higher than the 2-3% seen in other studies.[28] A simple, rough approximation of a patient's lifetime bleeding risk is 105 - (patient age in years), assuming a 3% bleed risk annually.[29] For example, a healthy 30-year-old patient would have approximately a 75% lifetime risk of at least one bleeding event. Ruptured AVMs are a significant source of morbidity and mortality; post rupture, as many as 29% of patients will die, and only 55% will be able to live independently.[7]

The annual new detection rate incidence of AVMs is approximately 1 per 100,000 a year. The point prevalence in adults is approximately 18 per 100,000.[3] AVMs are more common in males than females, although in females pregnancy may start or worsen symptoms due to the increase in blood flow and volume it usually brings.[30] There is a significant preponderance (15-20%) of AVM in patients with hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu syndrome).[29]

No randomized, controlled clinical trial has established a survival benefit for treating patients (either with open surgery or radiosurgery) with AVMs that have not yet bled.[31]