INTRACRANIAL VASCULAR MALFORMATIONS

Historical Review

Intracranial arteriovenous malformations were studied and classified as early as the mid-1800s (Luschka, 1854: Virchow. 1863). with the first surgical exposure of an arteriovenous malformation by Giordano occurring about three decades later in 1890. Fedor Krause attempted to surgically eliminate an arteriovenous malformation by ligating its feeding arteries in 1908 but Olivecrona appear, to have been the first to actually completely excise a cerebral arteriovenous malformation (AVM) in 1932 and later a cerebellar AVM in 1938.  Except at a few major centers. however, an aggressive surgical approach to the larger examples of these lesions have awaited the major technological advances of neurological surgery, neuroradiology, and neuroanesthesia during the past several decades.

Embryology of Arteriovenous Malformations

Arteriovenous malformation of the brain are congenital lesions most likely developing during the late somite stages of the fourth week of embryonic life and almost certainly no later than the eighth week. The primary pathologic lesion consists of one or more persisting direct connections between the arterial inflow and venous outflow without an intervening capillary bed.

Early in the third week of embryonic life, cells (angioblasts) begin to differentiate from the mesoderm, forming small, syncytial islands. These small clumps of syncytial cells develop tiny sprouts that extend to interconnect the cell groups, forming a syncytial plexus. Intercellular clefts appear within the syncytial masses. These clefts fuse to form the primitive vascular lumen. The syncytial cells enveloping these clefts become the endothelium of the new vessels. Proliferative growth of this endothelium links the vascular lumina into a continuous irregular endothelial vascular meshwork over the surface of the developing brain. Further extension of the primitive network, present over the developing telencephalon of human embryos at 4 weeks of age, occurs through endothelial sprouting.

Sabin has described a fascinating alternative process for the development of the primitive vascular plexus. She observed the appearance of intracellular vacuoles which coalesced to form the future vascular lumen, with the liquid of the vacuole becoming the primitive plasma. According to this schema, the first primitive vascular lumen is embryologically an intracellular structure, with the syncytial cell, containing these interconnected vacuoles forming the primitive vascular endothelium.

The primordial vascular plexus first differentiates into afferent, efferent, and capillary components over the more rostral portion of the embryonic brain. The more superficial portion of the plexus forms larger vascular channels. eventually evolving into the arteries and veins, with the deeper portion resolving into the capillary component more closely attached to the brain surface. Beginning circulation to the brain appears around the end of the fourth week of embryonic life. Arteriovenous malformations arise from persistent direct connections between the future arterial and venous sides of the primitive vascular plexus, with failure to develop an interposed capillary network .

During the sixth and seventh weeks the third pair of aortic arches, together with the dorsal aorta, transform into the primitive internal carotid arteries, with the first and second arches undergoing early involution. The vertebral arteries arise from a longitudi­nal linkage of the dorsal rami of the intersegmental arteries of the neck during the fourth week. All the original proximal intersegmental artery stalks except the most caudal one atrophy, resulting in a longitudinal vessel taking origin along with the subclavian from the sixth cervical intersegmental artery . The vertebral artery establishes communication with the internal carotids through the basilar artery, which arises independently through the consolidation of two longitudinal vascular channels beneath the brain. This linkage is established by the sixth week of fetal life. Between the sixth and eighth week of fetal life, a compartmentalized brain, dural and extracranial circulation has been established. By the eighth week of fetal life the major venous sinus pattern of the adult has begun to emerge.

Pathologic Classification of Arteriovenous Malformations

The development of cerebral angiography catalyzed interest in the study of intracranial vascular anomalies, providing the first major new insights into the pathophysiology of these lesions. The first major classifications of intracranial vascular malformations used extensively in the older European literature, consisted of four over­all categories: (1) angioma cavernosum, (2) angioma racemosum, (3) angioreticuloma and (4) angioglioma. Angioma racemosum included the subheadings of (a) telangiectasis, (b) Sturge-Weber syndrome, (c) angioma racemosum arteriale, (d) angioma racemosum venosum. and (e) arteriovenous aneurysm. The term "arteriovenous aneurysm" corresponds to the current designation "arteriovenous malformation."

In 1966 McCormick proposed a more clinically oriented categorization into five pathologic types: (1) telangiectasia, (2) varix, (3) cavernous angioma, (4) arteriovenous malformation and (5) venous angioma. Telangiectasias are capillary angiomas, usually small and solitary and most frequently occurring in the pons and the roof of the fourth ventricle. They are only occasionally associated with hemorrhage. A varix is usually quite small and is occasionally invisible grossly, consisting of one or more dilated veins not associated with an arteriovenous shunt. These small lesions, found in either the parenchyma or the leptomeninges, may be associated with hemorrhage, occasionally massive. Cavernous angiomas are dilated sinusoidal vascular anomalies varying in size or diameter from 1 mm up to many centimeters and are associated with hemorrhage as well as seizures. They occur most often in the cerebrum but may occur in any part of the central nervous system. Brain parenchyma is absent between the sinusoidal vascular spaces. Calcium deposition and hyalinization of the vessel walls are common: spontaneous thrombosis of either part or all of the lesion may occur. The blood in a cavernous angioma is not arterialized. The term venous angioma defines a malformation consisting entirely of veins not associated with an arteriovenous shunt, though otherwise closely resembling an arteriovenous malformation in gross appearance.

The term arteriovenous malformation, the primary topic here, refers to a congenital maldevelopment of blood vessels, with preservation of one or more primitive direct communications between arterial and venous channels. The malformations are found throughout the central nervous system, occurring most commonly in the cerebral hemispheres, with from 70 to 93 percent found in the supratentorial structures in various reported series. Arteriovenous malformations of the cerebral hemispheres most frequently involve the distribution of the middle cerebral arterial tree, followed in declining frequency by those of the anterior and then the posterior cerebral arteries. Hemispheral arteriovenous malformations can be further subclassified into those involving either one or a combination of the epicerebral, the transcerebral, and the subependymal circulations.

The epicerebral circulation consists of short perforating branches arising from the small pial arteries on the cortical surface and penetrating the cortex more or less at right angles to the brain surface. They form a distinct palisade of parallel short arteries of varying length, supplying the superficial, middle, and deep layers of the cortex. These slender cortical arteries show a grapnel-like pattern of branching, spreading outward and back upward toward the cortical surface as they terminate in a capillary bed. The longer transcerebral arteries (averaging 2 to 3 cm in length), traverse the cortex to feed an elongated capillary mesh or plexus paralleling the transcerebral arteries in the white matter. The transcerebral arteries terminate in the periventricular plexus.

Paralleling the arterial pattern, the venous drainage of the epicerebral circulation courses back outward to the veins on the pial surface. The venous drainage of the transcerebral arterial circulation is predominantly inward toward the subependymal venous plexus of the lateral ventricles, though anastomotic connections with and associated flow to the epicerebral veins are also present.

Malformations involving only the transcerebral arteries are not visible on the cortical surface, although it is common to see arterialized venous channels on the pial surface of the cortex as a result of the anastomotic connections between the transcerebral and epicerebral venous drainages.

Pathology

The gross appearance of an arteriovenous malformation is that of a tangled mass of dilated tortuous vessels. Small areas of hemosiderin staining and thickened, milky appearing pia-arachnoid are common in the immediate vicinity of the lesion in older patients. If the transcerebral circulation is involved in the malformation, the lesion presents a characteristic wedge-shaped appearance with the apex of the wedge at the ependymal surface of the lateral ventricle and the base of the wedge parallel to the overlying cerebral convexity. There is a rare but surgically very favorable group of arteriovenous malformations limited entirely to the pial surface of the brain stem.

Arteries emptying into the malformation become passively enlarged with time due to the high flow volume resulting from the abnormally low peripheral resistance of the A-V shunt. The venous system draining the shunt similarly undergoes progressive enlargement with increasing tortuosity as a result of the high flow volume and sustained increased venous pressure produced by the A-V shunt. Atrophic changes of the cortex and subcortical white matter in the immediate vicinity of the malformation are also common findings in older patients. Secondary changes with time have been found in the arterial walls of the feeding arteries in the immediate vicinity of the malformation, with collagenous replacement of the normal smooth muscle component of the media. Saccular aneurysms are an associated finding in between 10 and 15 percent of patients with arteriovenous malformations. Between 60 and 95 percent of these aneurysms occur on arteries hemodynamically related to the arteriovenous malformation.

The external carotid artery may make a significant flow contribution to a cerebral arteriovenous malformation and occasionally may be the sole source of arterial inflow to the lesion.

Incidence: Age and Sex Distribution

The cooperative study on intracranial aneurysms and arteriovenous malformations suggested that the frequency of intracranial arteriovenous malformations is about one-seventh that of saccular aneurysms. This would indicate that about 0.14 percent of the population harbor one of these lesions in a given year. The majority of lesions become symptomatic by the age of 40 and in most large series show no predilection for either sex. Although occasional reports of familial incidence are found in the literature, the larger series show no familial or genetic predisposition.

Clinical Features

In adult life the first symptom of an arteriovenous malformation is usually either a hemorrhage or a seizure, These two types of presentation occur with about equal frequency, The average age of onset for epilepsy as the initial symptom is about age 25, with age 30 the corresponding figure for hemorrhage. Patients with large arteriovenous malformations are more than twice as likely to have seizures in contrast to hemorrhage as their initial symptom, whereas the reverse is found for small lesions.

The reported incidence of headache from an arteriovenous malformation as an early symptom before the onset of either seizures or a hemorrhage range, from 5 to 35 percent. A pseudotumor syndrome secondary to elevated venous sinus pressure from large A-V shunts, particularly if the shunts are near the torcular and transverse sinus, and hydrocephalus as a sequelae to previously undiagnosed small subarachnoid hemorrhages are less common as a presenting feature. Arteriovenous malformations may occasionally mimic a demyelinating disease or brain tumor, particularly, when located in the brain stem or deep basal ganglia. Intellectual deterioration tends to occur with large AVMs in the older age groups. This deterioration appears to be at least partially related to a cerebral steal phenornenon.

In children. hemorrhage is seven times more likely than a seizure to be the initial presenting event. An additional common presentation of an arteriovenous malformation in the neonatal period is high-output left ventricular cardiac failure. Detailed hemodynamic studies have shown that right heart failure may evolve as an additional complicating factor secondary to right side overload from the left to right shunt.

The clinical course of an arteriovenous malformation, apart from hemorrhage, is usually one of slowly progressing symptomatology referable to the site of the lesion. The mortality rate from hemorrhage in the cooperative study was 10 percent from the initial bleeding episode. 13 percent from a second episode, and 20 percent from a third episode. The risk of recurrent hemorrhage after an initial bleeding episode is between 3.5 and 4.0 percent per year. The risk of hemorrhage in a patient presenting with cerebral seizures but with no known previous hemorrhage has been variously reported as between 1 and 2.3 percent per year. Forster et al. found. in a 15-year average follow-up of 35 patients presenting with epilepsy alone, a 17 percent mortality and 20 percent severe disability secondary to hemorrhage. They further noted that if the patient had had one hemorrhage, there was a 25 percent risk of rebleeding over the next 4 years. If there had been two previous hemorrhages, the risk for further rebleeding was 25 percent within the year following the most recent hemorrhage. A review of 137 patients treated conservatively with a follow-up period ranging from a minimum of 10 years to a maximum of 25 years found that only 20 percent of the 137 were alive and well at the end of the study. Thirty-seven patients either had died or were severely incapacitated by the arteriovenous malformation.

Vascular malformations presenting during pregnancy are more likely to rehemorrhage than those in the nonpregnant patients with the frequency of rebleeding approaching that of saccular aneurysms. The posthemorrhage mortality and morbidity figures, however, remain significantly lower than those for saccular aneurysms and comparable with those for the nonpregnant individual. Surprisingly, the timing of rebleeding does not appear to peak or parallel the cardiovascular changes in pregnancy. The peak incidence of hemorrhage from AVMs occurs between the fifteenth and twentieth week of pregnancy as compared with the peak incidence of aneurysm rebleeding between the thirteenth and fourteenth week of gestation. Only 2 of 77 AVM hemorrhages during pregnancy in this series occurred during labor. Elective cesarian section at 38 weeks gestation was thought to carry the smallest combined risk to mother and child.

Occasional spontaneous disappearance of intracranial arteriovenous malformations has been reported, but this remains a very rare occurrence.

Radiology

Cerebral angiography continues to be the definitive study for the assessment of intracranial vascular malformations. Careful bilateral carotid as well as vertebral angiography often demonstrates unexpected crossover or collateral filling of AVMs and is essential for adequate planning of therapy and assessment of risks to the patient. Computed tomography (CT) scanning or magnetic resonance imaging (MRI) have become common screening techniques for the diagnosis of vascular malformations. Angiographically occult AVMs have been found using both imaging techniques. Intracerebral hemorrhage enhancing on CT scan, even when arteriography fails to demonstrate a vascular anomaly, should raise the suspicion of the presence of a small AVM. Neither CT nor MRI reveals the anatomic detail necessary for surgical planning. They also do not reliably disclose the presence of associated vascular anomalies such as saccular aneurysms.

In a group of  patients with AVMs studied with unenhanced, enhanced, and 1-h postcontrast CT scans, the precontrast scan was abnormal in 81 percent of patients. 2% of patients showed a venous angioma on the immediate postcontrast scan, which was not apparent on either the precontrast or the 1-h delayed scan. The 1-h delayed scan revealed one angiographically occult, thrombosed AVM not seen on the precontrast or immediate postcontrast scan. The 1-h delayed scan also showed additional pathologic changes in areas adjacent to the lesions shown on the precontrast and immediate postcontrast scans. Delayed high-contrast CT scanning was judged to show no advantage as the routine screening procedure and, if done as a sole procedure, might miss at least some venous angiomas.

The "flow void" seen on MRI of AVMs has become a useful, though not completely accurate, technique for assessing the degree of occlusion of AVMs after focused stereotactic radiation therapy.

Indications for Operation

The role of surgery in the clinical management of a given patient is based on a composite of the probable natural history of the patients future clinical course, the risk of surgical management with particular reference to the patient's required occupational or daily activities, and finally, the patient's age. Patients in the older age group who have seizures but who are otherwise neurologically intact and without a previous history of hemorrhage have comparatively a smaller cumulative risk of major morbidity and mortality with continued conservative management. An important factor in long-term planning for the younger patient is the problem that seizure foci secondary to AVMs tend to become progressively more resistant to medical management with time. Although most current surgical series show some reduction in seizure tendency after malformation excision, extirpation of the malformation more importantly may block the further development of medically intractable seizure activity. In the younger patient, as is discussed in more detail below, the risk of mortality or major morbidity with surgery using current techniques is competitive with the 10-year prognosis for lesions that have not bled, and is better than the 5-year prognosis for malformations with a previous history of at least one hemorrhage. Malformations in areas of eloquent function are being found increasingly amenable to a surgical approach, with mortality or major morbidity risks of 10 percent or less. Deep lesions involving the internal capsule, thalamus, midbrain and lower brain stem are still usually found to be inoperable in terms of acceptable risks to neurological function.

Role of Embolization in AVM Management

Embolization of larger AVMs has become an important therapeutic adjunct to their surgical management. To date, the large majority of these lesions cannot be totally occluded by embolization techniques. Embolization does, however, permit a staged preoperative reduction in size of the arteriovenous shunt, producing significant circulatory readjustment and reducing the degree of hydraulic shock resulting from the final occlusion of the fistula at the time of surgical resection of the lesion. Embolization, when practical, has largely replaced staged surgical occlusion of the feeding arteries to achieve this effect.

Embolic agents are classified as either absorbable or nonabsorbable and as either solid or fluid. Solid embolic agents have been injected into the internal carotid or vertebral artery feeding the malformation, relying on the high-volume axial flow characteristics of the circulation to the AVM to carry the solid particles into its nidus. This technique is not satisfactory if the pellets, such as nonabsorbable barium-impregnated silicone spheres, have to leave the parent artery at a sharp angle to enter a branching vessel, such as would be required for a pellet entering the anterior cerebral artery from the internal carotid artery.

Gelfoam, cut into 1 x 2 mm strips, impregnated with tantalum powder and soaked in angiographic contrast material has been a common absorbable solid embolic agent. Although this material is relatively easy to handle. it has been more unpredictable in producing occlusion on the arterial side of the shunt and has no major advantages over silicone spheres.

Fluid embolic agents that have been employed have been nonabsorbable and of either the bucrylate or silicone types. Isobutyl-2­cyanoacrylate (ICBA) is a prototypic material of the bucrylate group. It is a rapidly polymerizing, low-viscosity tissue adhesive which is made radiopaque by adding tantalum powder. ICBA polymerizes rapidly on contact with ionic solutions such as blood or normal saline, while a 5% glucose solution will block polymerization. Considerable skill and experience are required in the use of this material. The speed of polymerization and rate of injection must be finely calculated to ensure that polymerization occurs on the arterial side of the malformation. Distal migration of this fluid into the major sinuses has occurred. If the arterial inflow is not arrested by polymerization on the arterial side of the shunt, sudden swelling and rupture of the malformation with major hemorrhage may occur. Bucrylate produces a foreign body giant cell reaction with chronic inflammatory changes not only in the vessel wall but also to a lesser degree in the adjacent brain parenchyma. The long-term effects of this material are not yet fully known, Occasional malformations have been completely occluded with bucrylate, although the success rate for total occlusion has not been high, There are several additional technical problems in using this material for occlusion of malformations in areas of eloquent function, Arterial branches to normally functioning eloquent cortex often depart from the parent artery distal to the first arterial branches going to the malformation. Total occlusion of the malformation would, of necessity, require sacrificing these normal branches, with potentially serious neurological sequelae. Additionally, the hardened, noncornpressible prongs of bucrylate within an incompletely occluded malformation may significantly increase the difficulty of subsequent safe separation and surgical removal of the malformation from areas of critical function.

Silicone fluid mixtures have occasionally been used instead of bucrylate. The mixture consists of a silastic elastomer containing a filler necessary for vulcanization. and a medical-grade silicone fluid that acts as the diluent to the more viscous Silastic elastomer. These two silicones are mixed to the desired viscosity and then tantalum powder is added to permit radiographic visualization. A catalyst to produce vulcanization is required. The Silastic is injected just before vulcanization occurs. It has no adhesive properties, so that a complete filling or cast of the vascular lumen is required.

After embolization with attendant reduction in the sump effect of the AVM, some patients have been noted to show improvement in intellectual performance, suggesting the correction of some degree of symptomatic cerebral steal. Wolpert et al. found, however, that embolization had no long-term effect on the progression of neurological symptoms or signs and no effect on seizure frequency. Incomplete occlusion of the malformation by embolization has not reduced or modified the natural history of the lesion with respect to hemorrhage.

In 1971, Serbinenko reported the use of detachable flow­directed balloons on the tips of catheters threaded into the proximal vessels to the malformation. This technique has been a key factor in permitting selective catheterization of these vessels for the injection of embolic agents but has not been a satisfactory therapeutic occlusive maneuver in and of itself.

Operative Management

Preoperatively, the patient is placed on an anti epileptic to minimize the risk of seizures during the early postoperative period of cerebral vasocongestion and cerebral swelling, even if the patient has no previous history of cerebral seizures. Serum antiepileptic levels are checked immediately before surgery to ensure that adequate antiepileptic levels are present. Dexamethasone is started 36 to 48 h preoperatively to help stabilize capillary membrane permeability during the early postoperative interval of hydraulic shock and local tissue reaction to surgical manipulation.

If the malformation lies in or immediately adjacent to the expected location of the motor cortex or major speech centers, the surgical procedure may be carried out under local anesthesia with cortical mapping to ensure accurate localization of the areas of eloquent function and to permit the testing of these functions serially throughout the removal of the malformation. In this latter situation, temporary clips are placed on the arterial feeders immediately proximal to the malformation, followed by function testing. The temporary clips are then replaced with permanent ones if no functional impairment has ensued.

Surgical resection should always be performed under magnification with appropriate microsurgical instrumentation. The dissection plane follows along the immediate margin of the malformation in the thin, gliotic nonfunctional zone between the malformation and the adjacent cortex and white matter. Particular care must be taken in occluding the small, thin-walled endothelial tubules composing the transcerebral venous drainage. These vessels are extremely fragile and, if torn, back-bleed profusely due to the increased venous pressure in the subependymal venous plexus from the A-V shunt. It is essential to avoid pursuing these vessels if unacceptable neurological deficit is to be avoided. Temporary placement of small fluffy cotton pledgets, accompanied by surgeon patience and by moving on to another area of the removal, will normally secure hemostasis of these individual venous bleeding points. Careful positioning of the head so that the major intracranial venous drainage is above heart level is a major factor in reducing venous congestion and attendant blood loss.

Selective identification and occlusion of the arterial inflow to the lesion with protection of the venous drainage as long as possible is important, although Malis advocates using one of the draining veins as a  'handle" and a guide to resection when several major draining wins are present. Major reduction in venous out­flow before interruption of the arterial inflow must be avoided if malformation rupture with massive bleeding is to be avoided. High-contrast visual dye can be injected intra-arterially to aid in the identification of the feeding arteries to the malformation if the vascular tangle of the malformation makes selective identification of the arterial inflow otherwise difficult. Significant fragility of the lesion persists down to the very end of the resection, making it essential that neither fatigue nor impatience results in a rush or hurry to complete the final stages of the removal.

A grid technique of localization of cortical function for a malformation lying in or adjacent to the central areas has been proposed by Kune. This technique presupposes a consistent pattern of cortical function with reference to standard anatomic landmarks. Experience with cortical mapping unfortunately has revealed significant deviation in location from the more common patterns of cortical function around the margins of arteriovenous malformations, especially with respect to speech localization. Modern techniques of anesthesiology have made a major contribution to increasing the safety of the surgical approach to,. and manipulation of these lesions. Moderate hypotension during critical periods of surgical resection is well tolerated, even under local anesthesia and does not interfere with patient alertness and function testing. The general anesthesia technique of jet ventilation can also essentially eliminate brain movement secondary to respiration.

Preliminary experience with surgical lasers used on intracranial vascular lesions has appeared in the literature. At present, the lasers seem to have limited application to the surgery of AVMs. This is particularly true of the CO₂ laser, which has relatively poor vessel coagulation ability because of its extremely shallow depth of penetration. The CO₂ laser tends to punch holes in the walls of larger vessels. The neodymium:YAG laser is more efficient in achieving hemostasis due to its greater depth or penetration. However, this latter laser type also is not effective in providing adequate hemostasis in dealing with the very thin-walled endothelial tubes of the engorged transcerebral circulation The neodymium:YAG laser appear, to provide adequate vascular occlusion when contractile elements are a significant component of the vessel walls being treated with the laser.

Gentle handling of the arteries proximal to the lesions is essential, particularly in the posterior fossa where proximal propagation of clot from the point of arterial occlusion can result In a disastrous outcome for an otherwise technically satisfactory surgical excision. After completion of the resection, the patient's blood pressure should be brought to normal levels and the operative field observed carefully to ensure that hemostasis is complete. Feeding arteries of 1 mm or larger must be securely clipped, if delayed postoperative hemorrhage is to be consistently avoided.  Bipolar coagulation alone for these larger vessels is not adequate.

Postoperatively, the patient is nursed with the head of the bed elevated 30 to 40 degrees to maintain optimal venous outflow. It is helpful to maintain the systolic blood pressure between 90 to 110 mmHg. using a trimethaphan camsylate drip, to minimize the effects of hydraulic shock and attendant hyperperfusion around the margins of the resection during the first 24 h postoperatively. Crystalloids are restricted in order to produce a mild dehydration, with the goal of a serum osmolarity between 295 and 305. Blood volume is maintained with colloid administration. Dexamethasone is continued postoperatively for 8 to 10 days and is then rapidly tapered. Postoperative angiography is essential to confirm that complete removal of the malformation has been achieved.

Results

The type of patient screening before surgical referral as well as the aggressiveness of the consulting neurological and neurosurgical units are obvious factors in reported results. In larger series in which over 60 percent of all patient, referred underwent surgical extirpation of the lesions, a mortality rate ranging from 7 to 14 percent is found.  The widespread use of the surgical microscope and the staged preoperative embolization of the lesions are major factor, in the improving mortality and morbidity statistics. Surgical mortality rates now appear to compare favorably with the long-term mortality rates of these lesions managed conservatively in the younger patient. More information regarding the quality of postoperative survival, as compared to the quality of life with conservative management. is needed, In the few instances where this information is beginning to appear, preliminary indications are that the long-term quality of life is more favorable when surgical extirpation of the lesion has been carried out.