This is a ten year old male who presents to the emergency department (ED) via ambulance, unconscious. His soccer coach accompanies him and reports that before practice began, he was complaining of a headache, and one hour later, he fell and began convulsing while practicing on the soccer field. A parent called 911. He seized for approximately five minutes. An ambulance arrived about 5 minutes later. An IV was started and he received phenytoin en route to the ED. His mother arrived shortly afterward, reporting that her son has a history of occasional headaches and that his teacher feels that he may have difficulty concentrating.

Exam: VS T 37.1, P 90, RR 24, BP 90/60, oxygen saturation 100% in room air. Height, weight, head circumference are at the 50th percentile. He is drowsy with a good respiratory effort. A contusion is noted on his left forehead. His pupils are equal and reactive. Auscultation reveals a bruit over the right eyeball. Ear and mouth examination is normal. Neck, heart, lung, and abdomen exams are normal. His muscle tone is diminished and his deep tendon reflexes are normal. He has a questionable Babinski sign bilaterally. His overall color and perfusion are good.

A CT scan demonstrates a large arteriovenous malformation (AVM) in the basal ganglia. He is admitted to the hospital. An MRI scan demonstrates that the AVM is most likely inoperable, and this is confirmed by angiography. The patient and his parents are warned of the possible risks associated with treatment of his AVM, and choose embolization as their treatment choice. Five years later, he dies due to a hemorrhagic stroke in his posterior cranial fossa.

An arteriovenous malformation (AVM) is defined as a tangled collection of abnormal blood vessels where there is an abnormal communication between the arterial and venous systems. They are not neoplastic despite their tendency to expand with time and the descriptive term "angioma" is occasionally applied. The afferents flow directly into the venous efferents without the usual resistance of an intervening capillary bed. They are mostly congenital. AVMs represent abnormal embryonic and fetal morphogenesis during the retiform stage of development of endothelial channels (approximately day 48 of human embryogenesis).

These lesions are neither neoplastic nor proliferative, rather growing commensurate with the child. If large enough, they may produce a shunt of sufficient magnitude to raise the cardiac output. In extreme circumstances, this can cause high output congestive heart failure. Common sites include skin, liver, brain, brainstem and spinal cord, where they may cause headaches, seizures or bleeding (subarachnoid hemorrhage). These lesions do not improve or resolve with time. In children, AVMs are the most common lesion associated with spontaneous hemorrhage. Only cerebral AVMs, of this broad classification, will be considered in this chapter.

Patients with small AVMs are more likely to present with hemorrhage than are those with large AVMs, partly because small AVMs are less likely to cause seizures and progressive neurologic deficit since a small cortical area is usually involved. About 40-60% of patients with an AVM present with hemorrhage, often with an intracerebral or intraventricular component. In comparison with saccular aneurysms, AVMs tend to bleed in younger patients, i.e. 20-40 years, and are less likely to have a fatal outcome. Lesions in the posterior fossa have a greater incidence of death from hemorrhage. The evidence is controversial as to whether patients who harbor an AVM that has bled are more likely to suffer further bleeds than those patients with other presentations.

Children present in a similar way to adults, but they may also present with high output cardiac failure if there is a high volume shunt, and they may rarely present with hydrocephalus. Approximately one third of patients present with seizures. Generalized or partial seizures commonly occur in patients with AVMs, especially if the lesion involves the cortical surface. Of patients presenting with hemorrhage, 30% have a history of epilepsy. Lesions close to the Rolandic fissure are particularly likely to present with seizures. About 10% of patients present with neurological deficit. This typically includes cognitive deficits and memory problems. However, some patients develop gradual weakness or visual loss.

Large AVMs, especially those involving the basal ganglia, may present with a slowly progressive dementia, hemiparesis or visual field defect, probably as a result of a "steal" effect, in which blood is shunted away from functional cerebral areas. The infrequent brain stem AVM may also produce a motor or sensory deficit, with or without cranial nerve involvement. Attacks of well localized headaches (unilateral and throbbing) occur in a proportion of patients subsequently shown to have a large AVM. Auscultation, especially over the eyeball, occasionally reveals a bruit.

Capillary vascular malformations are initially pale with normal overlying skin texture but may darken as the patient ages. Nodularity and a darker purple pigmentation may occur in adulthood due to increasing dilation of the dermal vessels. AVMs may demonstrate increased warmth, audible bruits, palpable thrills, or visible pulsations. Hypertrophy of the involved limb or structure may be apparent.

Other problems to consider when doing the work-up for AVMs, include Kasabach-Merritt syndrome, vein of Galen malformation, and Sturge-Weber syndrome. Kasabach-Merritt syndrome is a capillary hemangioma associated with platelet consumption resulting in thrombocytopenia and progressively enlarging vascular malformations which may involve large portions of their extremities. Bleeding commonly develops in the first year of life, secondary to chronic disseminated intravascular coagulation triggered by stagnant blood flow through the tortuous abnormal vessels. Anemia is caused by red cell damage as blood passes through deformed vessels of the tumor.

The vein of Galen is located under the cerebral hemispheres and drains the anterior and central regions of the brain into the sinuses of the posterior cerebral fossa. Aneurysmal malformation of the vein of Galen (a type of AVM with a dilated Galenic system serving as the venous outflow for an adjacent adenoma) typically results in high output congestive heart failure in neonates resulting from the decreased resistance and high blood flow in the lesion, or this may present later with developmental delay, hydrocephalus, and seizures.

Angiomatosis affecting the facial skin, eyes, and leptomeninges produces the characteristic features of the Sturge-Weber syndrome, which is characterized by capillary nevus over the forehead and eye, epilepsy and intracranial calcification. There is no clear pattern of inheritance. Practically all cases are sporadic, and many are associated with occipital AVMs. Epilepsy occurs in 75% usually presenting in infancy. Hemiparesis, homonymous hemianopia occur in 30%, and behavioral disorders with mental retardation occur in 50%.

Most AVMs are evident on CT scan unless masked by the presence of an intracranial hematoma. A double dose of intravenous contrast may aid visualization, especially with small lesions. Following IV contrast, streaks of enhancement representing dilated feeding and draining vessels, irregular lesions strongly enhancing with contrast, and calcification may be apparent. Conventional MRI will clearly demonstrate the AVM, with associated signal change within or around the lesion from areas of old hemorrhage or gliosis. MRI is the investigation of choice in identifying cavernous vascular malformations (a rare, often congenital disorder of the venous system in which the hemangioma is a mass resembling a tumor, consisting of large blood-filled spaces which can occur at any site in the body). These are often missed on unenhanced CT scanning because it may be isodense with the surrounding brain. Most lesions show marked signal change around this lesion due to a rim of hemosiderin deposition. Four-vessel angiography confirms the presence of an AVM and delineates the feeding and draining vessels. Occasionally small AVMs are difficult to detect and only early venous filling may draw attention to their presence. In the presence of a hematoma, angiography should be delayed until the hematoma resolves, otherwise local pressure and surrounding hemorrhage may mask demonstration of an AVM. If the angiogram is subsequently negative, then MRI is required to exclude the presence of a cavernous malformation.

Patients presenting with AVMs pose the clinician with difficult management choices. First, there is no consensus as to how AVMs should be classified or even defined. The natural history of an AVM is hard to predict. There are three disciplines, surgery, interventional radiology and radiation therapy, all offering their own treatments and with some disagreement as to which treatment modality is superior.

The various methods of treating AVMs all risk further damage. The urgency of the patient's clinical condition and the risks of treatment must be weighed against the risk of a conservative approach. Indications for intervention include: 1) expanding hematoma associated with the AVM, 2) progressive neurological defect, and 3) high risk of hemorrhage especially in younger patients (with many years of future risk), with the AVM less than 3 cm in diameter and in a non-eloquent site. "Eloquent" is a term used to indicate that the anatomic brain location is very important for vital neurological functions such as movement, language, and memory. Non-eloquent refers to brain areas that can be injured or removed without significant functional neurological deficit. Operative removal may not benefit epilepsy control.

Methods of treatment include operation (excision), stereotactic radiotherapy, embolization, and occlusion of feeding vessels. Complete excision of the AVM (confirmed by pre- or postoperative angiography) is the most effective method of treatment. Image guided surgery may aid localization of small AVMs or cavernous malformations. Some deeply situated lesions in the basal ganglia or brain stem are inoperable in view of the risk of neurologic deficit.

Standard radiotherapy is of no value in the treatment of AVMs, but focused beams either from multiple cobalt sources or from a linear accelerator, can obliterate up to 80% of lesions under 3 cm in diameter within two years of treatment. Results are far less encouraging for larger lesions, although combinations of embolization and stereotactic radiotherapy may provide an alternative treatment method for large inoperable AVMs in the future. Although avoiding direct operative damage, stereotactic irradiation destroys tissue locally at the target site. The larger the dose, the greater the chance of AVM obliteration, but the greater the risk of neurological deficit from local tissue destruction. A further disadvantage is the possible delay of up to two years before obliteration occurs. Despite this, stereotactic irradiation may prove ideal for some deeply situated lesions.

Skilled catheterization permits selective embolization of feeding vessels with isobutyl-cyanoacrylate, although this technique is not without risk. Embolization alone is unlikely to produce complete obliteration, but if used preoperatively, it may significantly aid operative removal. Occlusion of feeding vessels, whether by direct operation or by an endovascular balloon, fails to prevent persistent filling of the AVM because of the development of collateral vascularization.

Prognosis varies greatly with severity and presentation. Vasospasm and delayed ischemic complications rarely develop. Generally speaking, small AVMs are a greater risk of bleeding than larger lesions. The risk of initial and recurrent bleeding over a 5-year period in patients with a previously unruptured AVMs is approximately 15% (i.e. 2-3% per year); however, the risk increases to 50% over 5 years for lesions under 3 cm in size. After hemorrhage, the chance of a further bleed is slightly increased in the first year but beyond that, the risk reverts to that of an unruptured AVM. In contrast to the high mortality following aneurysm rupture, hemorrhage from an AVM carries the relatively low mortality rate of approximately 10-20%.

Questions

1. True/False: AVMs represent abnormal embryonic and fetal morphogenesis during the retiform stage of development of endothelial channels (approximately day 48 of human embryogenesis).

2. All of the following are used in the treatment of AVMs except:
. . . . . a. Excision
. . . . . b. Stereotactic radiotherapy
. . . . . c. Embolization
. . . . . d. Cryotherapy
. . . . . e. Occlusion of feeding vessels

3. True/False: The rare AVM that produces a very enlarged "vein of Galen aneurysm" can cause heart failure in infancy as a result of large volume blood flow through the shunt.

4. True/False: Occipital AVMs are frequently associated with hemangiomas of the face (Sturge-Weber syndrome).

5. True/False: The decision to treat an individual patient with an AVM requires balancing the natural history of the disease and in particular, the risk of hemorrhage against the risk of an interventional procedure.

6. True/False: Significantly decreased perfusion pressure is uncommon in areas adjacent to an AVM.

References

1. Fuchs S. Ch. 42-Cerebrovascular Syndromes. In: Strange GR, Ahrens W, Lelyveld S, Schafermeyer R (eds). Pediatric Emergency Medicine. 1996, New York: McGraw-Hill Companies, p. 251.

2. Lindsay KW, Bone I. Neurology and Neurosurgery Illustrated, third edition. 1999, New York: Churchill Livingstone, pp. 288-292.

3. Bergman I, Painter MJ. Ch. 18-Neurology. In: Behrman RE, Kliegman RM, et al (eds). Nelson Essentials of Pediatrics, fourth edition. 2002, Philadelphia: W.B. Saunders, pp. 781-782.

4. O'Doherty DS, Fermaglich JL. Handbook of Neurologic Emergencies. 1977, New York: Medical Examination Publishing Company, p. 221.

5. Sellar RJ. Ch. 5- Cerebral Arteriovenous Malformations. In: Butler P (ed). Endovascular Neurosurgery, A Multidisciplinary Approach. 2000, London: Springer-Verlag London Limited, pp. 73-96.

6. Brown RD. Ch. 7-Epidemiology and Natural History of Vascular Malformations of the Central Nervous System. In: Jafar JJ, Awad IA, Rosenwasser R (eds). Vascular Malformations of the Central Nervous System. 1999, Philadelphia: Lippincott Williams & Wilkins, pp. 129-148.

Answers to questions

1. True, 2. d, 3.True, 4.True, 5.True, 6.False