Congenital vascular malformations in childhood

Congenital Vascular Malformations in Childhood Ignacio PascuaI-Castroviejo and Samuel-lgnacio PascuaI-Pascual Congenital vascular malformations are an important group of vascular anomalies that occur very early in the pregnancy. Most of these malformations occur between the third and the seventh weeks of the embryonic development. Malformations can affect the arteries, veins, capillaries, and venous sinuses, involving an isolated vessel or a part of the vascular system. There are malformations that affect the vessel size or course, and others that show pathology of the wall anatomy of the vessel. Magnetic resonance angiography (MRA) is improving the study conditions of this pathology. Treatment of most of the vascular malformations--some of them giving clinical symptoms during adulthOOdmstill constitutes a challenge.

Copyright 2002, Elsevier Science (USA). A l l rights reserved.

ONGENITAL VASCULAR malformations are defined as (1) the absence of vessels that usually are present; (2) the presence of vessels usually not appearing postnatally; (3) or the presence of vessels of abnormal morphology or size, abnormalities of arterial, capillary, or venous walls, occurring singly or combining some of all structures. The principal congenital vascular anomalies are seen in the Table 1. The importance of these changes is determined by a frequent occurrence in association with internal or external anatomic anomalies and with intracranial pathology caused directly by the vascular malformation (eg, hemorrhage in aneurysms or arteriovenous malformations, ischemia, and also hemorrhage in moyamoya), or caused by deficient collateral vascularization (eg, obstruction of an intracranial artery in the case of congenital absence of another artery). The existence of intracranial vascular anomalies has been known for more than a century, the first descriptions corresponding to anatomic findings] However, the history of the knowledge of the vascular pathology began with Egas Moniz who described the conventional arteriography by the direct injection of a contrast substance into the arteries, which permitted the visualization of normal and abnormal intracranial vessels in vivo. z

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CONGENITAL ARTERIAL ANOMALIES There are anomalies, which appear in a high percentage of cases, that are considered variations From Pediatric Neurology Service, University Children's Hospital "La Paz," Madrid, Spain. Address reprint requests to Ignacio Pascual-Castroviejo, MD, PhD, Hospital de NbTos "La Paz, " Servicio de Neurologia lnfantil, Paseo de la Castellana 261, E-28046 Madrid, Spain. Copyright O, Elsevier Science (USA). All rights reserved. 1071-9091/-2000/000-0535.00/0 dzfi:lO.1053/spen.2002.32503 254

of normal because they do not cause clinical problems, at least during childhood. However, others may represent a threat because of its frequent association with other types of pathology, the risk of bleeding, or many other reasons.

EMBRYOLOGIC DEVELOPMENT To understand the several anomalies of the extracranial and intracranial vessels, it is necessary to make a chronologic summary of the embryonic development of the cerebral arteries, including both their origin at the aortic arch and the intracranial trajectories, and the ontogeny of their cerebral vasculature. 3-6 All of the arteries that provide vascularization of the brain begin their development in the aortic arch. Two stages of this development are recognized: the primary or brachial stage that appears at about 22 days, which shows the appearance of a vascular apparatus destined to become the precursor of the posterior arteries; the second or postbrachial stage in which the vascular apparatus mentioned is replaced by the adult arterial system during a period lasting about 28 days. The brachial stage begins with the formation of the first aortic arch and terminates somewhat arbitrarily with interruption of the sixth arch. The sequence in the appearance of the different structures is developed between the appearance of the first aortic arch in the human embryo of 1.5 mm (3 weeks) and that of the sixth aortic arch in the embryo of 5 mm (4.5 weeks). The formative process is sequential, and the appearance of one aortic arch follows the disappearance of the previous. The third arch of each side contributes to the development of the common and internal carotid arteries in the embryo of 3 mm, during the third and last phase of the brachial stage. With a length of approximately 7 to 12 mm (32 to 35 days) the internal carotid artery already shows filling with blood in its intracerebral

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Table 1. Congenital Vascular Malformations in Childhood A. Congenital arterial anomalies 1. Nonpathologic abnormalities of the arteries originating at the circle of Willis. 2. Nonpathologic morphology abnormalities of extra and intracranial arteries. a. Coiling or kinking at the neck. b. Fenestration of arteries. 3. Morphologic abnormalities that may or may not be pathological. a. Carotid or vertebral hypoplasia. b. Megadolicoarteries. 4. Persistence of embryonary arteries. a. Trigeminal. b. Hypoglosal. c. Stapedial. d. Bernasconi--Cassinari. 5. Absence of cerebral arteries. 6. Congenital malformations of arterial walls. a. Moyamoya disease. b. Fibromuscular dysplasia. c. Intracranial aneurysms. B. Cerebrovascular anomalies. 1. Arteriovenous malformations. 2. Venous angiomas. 3. Capillary telangiectases. 4. Vein of Galen malformations. 5. Intracranial cavernous malformations. 6. Cortical venous anomalies. a. Vascular malformations of the leptomeninges. b. Dural arteriovenous malformations. c. Aneurysmatic dilatation of the torcula. d. Sinus pericranii.

course; when the embryo is 12 mm to 14 mm (35 to 38 days), the common carotid artery may be identified and for the first time the cerebral ramification of the internal carotid artery and of its collateral vessels may be described as the earliest adult configuration. When the embryo is 3 mm (3.5 weeks), the trigeminal artery begins to sprout from the first aortic arch. It constitutes the first source of blood supply to the posterior part of the primordial brain. The formation of the basilar artery is accompanied by the involution of the trigeminal or its annexation by the internal carotid. When the trigeminal artery persists after birth, it constitutes an important vascular malformation anastomosing the internal carotid system with the basilar artery, a function normally substituted by the posterior communicating arteries. The vertebral arteries begin to form when the embryo is 9 mm (32 days) by longitudinal anastomosis between superior longitudinal segmental arms of the dorsal aorta with

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subsequent obliteration of all aortic connections except those of the seventh cervical segmental arches, which remain as the subclavian trunk. The vertebral arteries terminate their maturity when the embryo reaches 14 mm to 16 mm (between 36 and 40 days), with their origin having been displaced from the wall of the aorta to the level of the ductus arteriosus. NONPATHOLOGIC ABNORMALITIES OF THE ARTERIES ORIGINATING AT THE CIRCLE OF WILLIS

Most often it concerns to nonpathologic variations of the anatomic configuration, without influencing the blood supply of the brain. The main variations are (1) the origin of one or both posterior cerebral arteries from the internal carotids, (2) the origin of both anterior cerebral arteries from the same internal carotid, and (3) important differences in size of both internal carotids, both anterior cerebral arteries, both posterior cerebral arteries, or both posterior communicating arteries. In these cases the vascular deficit caused by the narrow artery of one side is compensated by an increase in the size of the other (Fig 1). Some 28 different normal anatomic variations of the circle of Willis are described. 7 However, asymmetric configuration of the circle of Willis appears less frequently in embryos than in adults. 8

Fig 1. The MRA reveals important differences in the size of the internal carotid arteries, that narrowing on the right side and widening on the left.

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MORPHOLOGIC ABNORMALITIES THAT MAY OR MAY NOT BE PATHOLOGICAL

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The two main types are carotid or vertebral hypoplasia and megadolicoarteries. 1. Carotid or vertebral hypoplasia. This is an anomaly that often is associated with neurocutaneous diseases, especially with neurofibromatosis typel ~2 and cutaneous facial or neck hemangioma or vascular malformation as a part of the syndrome described by Pascual-Castroviejo in 1978.13 However, the presence of this anomaly is mostly incidentally seen during angiographic study for any disease because of the lack of neurological symptoms due to the good collateral vascular compensation through branches of other intracranial and extracranial arteries (Fig 4). Still rarer is the presence of the carotid bifurcation at an asymmetrical venous level. 2. Megadolicoarteries. This anomaly consists of a pathologic congenital dilatation of the arterial

Fig 2. Conventional arteriography of the vertebrobasilar system shows many incurvations and generalized elongation of the extracranial and intracranial arterial trajectories.

NONPATHOLOGIC MORPHOLOGY ABNORMALITIES OF EXTRACRANIAL AND INTRACRANIAL ARTERIES

Apart from the generalized elongation of the arteries in Menkes disease (Fig 2), most anomalies of this group are incidental angiographic findings. The most common varieties are as follows: 1. Carotid or vertebral coiling or kinking at the neck (Fig 3). This anomaly is seen in 25% of children below 8 years and in a 50% of cases of Sturge-Weber syndrome. 9 In the adult, it has been associated with stroke because of obstruction of the kinked or coiled arterial zone. ~~ 2. Fenestration of arteries. This is also known as arterial duplication. It is a very rare anomaly and only involves a short part of the arterial course. It presents more frequently in the vertebrobasilar territory, but also occasionally may be seen in the carotid system. 11

Fig 3. Conventional arteriography shows double kinking in the extracranial part of the internal carotid artery (star).

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1. Persistence of the trigeminal artery. When the trigeminal artery presents after birth, it communicates the internal carotid system with the basilar artery (Fig 7), a function normally sub-

Fig 4. The MRA of the neck in a case with left facial and cervical hemangioma, discloses an asymmetrical carotid bifurcation (stars), and hypoplastic right artery.

lumen with increasing of the course that has to follow the artery giving the effect that it is too long for the rejection that has marked in the brain. It may be seen as an isolated finding, but also as part of a disease of increased development of surrounding structures--skin, conjunctival tissue, or bones--as one more complication of a neurocutaneous disease. We have found this anomaly in cases of hypomelanosis of Ito ipsilateral to the hemifacial hypertrophy, and also associated with the facial hemangioma described.14 However, megadolicoartery associated with facial or neck hemangioma shows a parallel process of increasing the arterial lumen during some months or years (Fig 5) and decreasing in a second period that is prolonged over several years, similar to that followed by the cutaneous hemangioma (Fig 6). The intracranial arteries with a very wide lumen during the first years of life may appear very narrow or occluded after several years. 14 Isolated megaartery, especially the basilar artery, can compress cranial nerves 15 or the brainstem ~6 along its trajectory in the posterior fossa. PERSISTENCE OF EMBRYONARY ARTERIES

Some of the embryonic arteries that supply the brain during the first weeks of the intrauterine development persist after birth. Most often their presence may appear to be incidental, but they are often--perhaps almost always--associated with some type of pathology. Apart from the persistence of the trigeminal artery, the presence of an embryonic artery, such as the hypoglosal, the otic, or the Bernasconi-Cassinari arteries, is very rare.

Fig 5. (A) Facial hemangioma on the right side of the face at 10 months of age. (B) The conventional arteriography at the age of 10 months shows dilatation and tortuosity of the intracranial trajectory of the internal right carotid artery and its branches.

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complete in the embryo of 14 mm (5 to 5.5 weeks). This anomaly has been described in 0.1% to 0.6% of the largest series of angiographic studies. 17 However, persistence of the trigeminal artery is seen in a 30% in cases of facial and neck hemangioma. 14 2. Persistence of the hypoglossal artery. This is a rare anomaly. It has been seen in a 0.25% of important angiographic series.IS It may be associated with severe encephalopathy and cerebellar malformation. 19 The hypoglossal artery is an anomaly that consists of the presence of an artery that originates in the internal carotid artery at the level of the second cervical vertebra and follows intracranially as the basilar artery (Fig 8). The posterior inferior cerebellar artery (PICA) may be absent bilaterally. 19 3. Persistence of the stapedial artery. This anomaly is originated of the hyoid at about 4 to 5 weeks of the embryo. When the embryo is 12 to 15 mm, the stapedial artery is devided in a dorsal branch that will form the middle meningeal artery, and a ventral branch that will form the maxillary and mandibular arteries. Both hyoid and stapedial arteries disappear at about the third fetal week. The presence of the stapedial artery is an incidental angiographic finding. We have seen persistence of the stapedial artery associated with auricular dysplasia. 2~ This anomaly has been described in association with absence of the internal carotid artery on one side and of the external carotid artery on the other. 21 4. Artery of Bernasconi-Cassinari. This is an embryonic tentorial vessel that was first described as a typical sign of tentorial meningioma. It can

Fig 6. (A) The same patient as in Fig 5 at 28 years of age. The facial hemangiomatous skin appears very atrophic. (B) The MRA at 28 years of age shows the intracranial arteries with very decreased arterial lumen, disappearance of the pericallosal artery, a persistent trigeminal artery (arrow) and collateral vascularization (arrowhead).

stituted by the posterior communicating artery. The formation of the basilar artery is accompanied by involution of the trigeminal artery or its annexation by the internal carotid, becoming

Fig 7. MRA shows the persistence of the trigeminal artery (arrowhead) in a case with ipsilateral facial hemangioma.

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malformation on the neck, scalp, or facial regions, usually located on the same side of the vascular malformations (Fig 9). 13.14 CONGENITAL MALFORMATIONS OF THE ARTERIAL WALLS

Moyamoya disease

Fig 8. Conventional arteriography shows a persistent hypoglossal artery that originates in the internal carotid artery (arrow).

be seen in patients with tentorial meningioma of any age as well as in other types of vascular disease of the brain, such as moyamoya disease. 22 This artery originates from the first intracranial portion of the internal carotid artery and courses laterally to the mesencephalon to arrive to the tentorium (Fig 9). ABSENCE OF CEREBRAL ARTERIES

Absence of one carotid or one vertebral artery rarely is associated with neurological disease, which is probably due to the good supply through the collateral circulation. 14"23"24Agenesis, aplasia, and hypoplasia of an internal carotid artery are rare congenital anomalies occurring in less than 0.01% of the population. 25'26 The prevalence of absence of an internal carotid artery in cases of facial hemangioma is a 25% and of a vertebral artery is 35%. 14"24 Cases of absence of both carotids without severe encephalopathy have been reported. 25'27 We studied a case with absence of both vertebrals associated with almost complete cerebellar aplasia that showed severe motor disease. The external carotid artery also can be absent in cases of facial hemangioma. ~4 Many cases with absence or hypoplasia of one carotid or one vertebral artery have shown a facial, neck, or scalp hemangioma or vascular malformation during the first years of life that usually disappeared. The association of the absence of a cerebral artery--carotid or verteb r a l - w i t h the presence of an embryonic artery, mainly the trigeminal, usually corresponds to cases that show or have shown hemangioma or vascular

This is an occlusive disease of the circle of Willis characterized by bilateral stenosis or occlusion of the terminal portion of the internal carotid artery and by the development of abnormal netlike vessels at the base of the brain (moyamoya phenomenon). At the same time, collateral circulation gradually develops as a result of the occlusion of the carotid fork at a younger age. Moyamoya disease occurs more frequently in females. It is found at any age, but is most prevalent in children. Although moyamoya disease is described more frequently by Asians, especially by the Japanese, and it perhaps has a higher incidence in Japan and Korea, its presence among people of Westerns countries also is considerable. Children and juvenile patients with moyamoya disease initially present with ischemic symptoms such as transient ischemic attacks, completed strokes, and subsequent motor or intellectual impairments. Adults, by contrast, present with intracranial hemorrhage. The symptoms in children are due to the narrowing or occlusion of proximal intracranial trajectory of the main arteries, whereas in adults symptoms are due to a collapse of collateral circulation, especially transdural vasculariza-

Fig 9. Conventional carotid arteriography shows the artery of Bemasconi-Cassinari associated with moyamoya disease.

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tion, that gradually develops as a result of the occlusion of the carotid fork at an earlier age. The terminal portions of the internal carotid artery, the middle cerebral artery, and the anterior cerebral artery are stenotic or occluded, whereas the posterior cerebral arteries usually are not involved. Therefore, regional cerebral blood flow decreases mainly in the operculum and in the frontal lobe, whereas the vascularization of the occipital lobe is preserved. About 10% of patients with moyamoya disease have a family history of the disease98'29 In Japan, approximately 70% of cases among family members occur in siblings, and 24% occur in a parent and offspring, and occurrence in parents and siblings of patients with moyamoya disease is 30- to 40-fold higher than in general population. 3~ Descriptions of the presence of persistent embryonic arteries fulfill a collateral vascularization 22 and may indicate the early time in which the disease starts. Although moyamoya disease has long been thought to be caused mainly by environmental factors, molecular genetic studies performed during the last few years demonstrate a linkage between the disease and markers located at 3 p24.2p26, 3~ 17q25, 32 and 633 in families affected of moyamoya disease. An association of neurofibromatosis type 1 with moyamoya disease is demonstrated in children and adults. 34'35 The diagnosis of moyamoya disease is based on angiographic features that consist on stenotic or occlusive changes of the supraclinoid portion of the internal carotid artery on both sides, frequently extended to the proximal portions of the anterior and middle cerebral arteries, abnormal netlike vessel formations at the base of the brain (moyamoya images), and development of extracranial and intracranial transdural leptomeningeal collaterals between the pial vessels and those arising from the branches of external carotid artery, which include the occipital artery, superficial temporal, and meningeal branches of the internal maxillary artery. Collateral vascularization usually develops between intracranial branches of the internal carotid, especially the anterior and posterior branches of the ophthalmic artery that usually is very enlarged, and least frequently between the persistent embryonic vertebrobasilar systems, especially those arising from the posterior cerebral arteries, such as the posterior pericallosal artery. Abnormal net-like

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vessel formations can be found anywhere intracranially, but the most typical are those arising bilaterally at the base of the brain, contributed to by most of the arteries that usually supply perforating, lenticulostriate, thalamostriate, and premammillary as well as other vessels of the newly formed circle of Willis. Conventional arteriography can demonstrate all the described vascular changes. However, magnetic resonance arteriography (MRA) has the advantage of showing, at the same time, all alterations described in the territories of both carotid and basilar systems without using contrast material. Moreover, in the same study, it is possible to know the presence of ischemic zones in the brain. Suzuki and Takaku 36 divided angiographic features into six stages in terms of the progression of the carotid fork occlusion: (1) narrowing of carotid bifurcation; (2) beginning of moyamoya; (3) intensification of moyamoya; (4) minimization of moyamoya; (5) reduction of moyamoya; (6) disappearance of moyamoya. The mean hemispheric cerebral blood flow (mCBF) of the pediatric moyamoya patients in the entire hemisphere has been found to be similar to that of normal subjects in some publications 37 and decreased in others. 38 The pathogenesis of moyamoya disease is enigmatic. There are two major hypotheses, genetic and acquired. The latter etiology mainly includes infection through autoimmune responses. An epidemiologic study on moyamoya disease in Hawaii, with a population of diverse ethnic origins, showed a higher incidence and prevalence than in the rest of the United States, mostly owing to the larger percentage of Asians, particularly Japanese, living in Hawaii. 13"39 These epidemiologic data suggest that moyamoya disease is caused by genetic, rather than environmental, factors. Both medical and surgical therapies have been used. Vasodilators, costicosteroids, antiplatelet agents, calcium antagonists, and low-molecularweight dextran have been used, but their efficacy is difficult to assess. Various surgical treatments have been used in pediatric patients, including direct bypass surgery, such as superficial temporal artery to middle cerebral artery, 4~ and indirect bypass surgery, such as encephalo-duro-arterio-myosynangiosis. 41 It is difficult to compare the results obtained with medical and surgical treatments. However, during the last years, Asian authors report good results in children using any of these

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reported techniques, especially with encephaloduro-arterio-myo-synangiosis. 42-44 Surgical results are better in children than in adults. 45 The long-term evolution of patients with moyamoya disease is poorly documented. 46 Cases presenting before the age of 4 years are associated with a worse prognosis. 47 Complications or changes in the neurological status at some time during the pregnancy or at delivery has been observed in 80 percent of women. 48 We have only one patient who showed symptoms of psychomotor retardation from the first year of age and follow-up over a period of 38 years. She had a normal pregnancy and delivery at 26 years of age without complication. 49 She was treated only with nicardipine, the effectiveness of which is uncertain.

Fibromuscular dysplasia Fibromuscular dysplasia (FMD) also known as fibromuscular hyperplasia is a noninflammatory segmental arteriopathy of unknown origin. It is encountered most often in adult women and is rare in children. Although the disease can involve any artery of the body, it mostly affects the renal arteries, followed by the mesenteric, carotid, or vertebral arteries. Generalized FMD has been occasionally reported. 5~ FMD is frequently reported in adults because of stroke, and rarely in children, also related to stroke, and during sex, almost always in women. Caucasians show a racial predisposition, 51 as do people with hereditary disorders of connective tissue or with Ehlers-Danlos syndrome. 52 Affected girls usually show very feminine phenotype, which is similar to their mothers. These women and girls exhibit a thin, tall body with hyperextension of the joints. Symptoms of cervicocephalic FMD include stroke, seizures, and motor disturbances. Ischemic infarction in the cerebral region supplied by the affected artery is the most common sequela. Internal carotid, middle, and anterior cerebral arteries are the most commonly affected vessels. The diagnosis is made on the basis of the characteristic radiographic changes. Conventional angiography and MRA disclose narrowing or occlusion of the affected arteries, which exhibit the appearance of "string of beads" that correspond to zones of stenosis alternating with abnormally wide poststenotic arterial areas; MRA has several advantages over conventional angiography (Fig 10). The most important are the possibility of a good

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Fig 10. The MRA in coronal view shows a narrow right internal carotid artery and its intracranial branches that also exhibit an appearance of a "string of beads",

visualization of all extracranial and intracranial arteries in the same study without using contrast, and the fact that it is less invasive and less dangerous. Pathologic angiographic manifestations include four subtypes. 5~ 1. Medial fibroplasias: This is the most common finding. Its shows an accumulation of dysplastic fibrous tissue in the media, though it can involve the external lamina as well. 2. Intimal fibroplasias: subendothelial mesenchymal cells accumulate within the fibrous tissue. 3. Perimedial dysplasia: elastic tissue underlying the advential layer increases pathologically. 4. Medial muscular hyperplasia: smooth muscle hyperplasia occurs without fibrosis within the media. The cause of intracranial FMD is not yet known. Increased familial incidence points to the role of genetic predisposition, 55 but other possibilities, such as trauma, hormonal defects, infection, and toxic injury to the endothelium, have been suggested as well. During recent years, the association of intracranial aneurysms in 20% to 50% of patients with FMD, the possible link between FMD and alphal-antitrypsin deficiency in children with this disorder, and the possible role of alpha~-antytrypsin deficiency in the rupture of intracranial or abdominal vessels and arterial dissection 55-59 suggest that the cause of FMD could be an underlying congenital connective tissue disorder. The disorder shows a variable evolution. Most of our cases have a chronic course, but we also have a few cases with spontaneous resolution of internal carotid FMD. Progression has been dem-

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Fig 11. The coronal view of the three-dimensional MRA shows an aneurysm (asterisk) with a wide neck in the proximal zone of the right middle cerebral artery.

onstrated in most adult patients. 5~ Treatment of FMD of the intracranial carotid artery or its intracranial branches consists of the use of aspirin, antiplatelet therapy, or calcium antagonists, especially nicardipin or nimodipin. Surgical treatment is not common for the carotids or its intracranial branches, but it has been used for renal and other arteries with FMD.

Intracranial aneurysms Primary intracranial aneurysms of either the vertebrobasilar or the carotid arteries and their branches are rare at any age in pediatric patients. However, in support of the congenital origin of intracranial aneurysms is the fact that anomalies of the circle of Willis are commonly associated with intracranial aneurysms. Intracranial hemorrhages caused by aneurysms are extremely rare. Aneurysms consist of a pathologic and localized dilatation of a small part of the arterial wall due to a congenital defect of the elastic or the media layers. The incidence of intracranial aneurysms is more than twice in women than in men, 6~ especially in those of saccular type. Most aneurysms are small, but they may be of any size, including giant ones. Aneurysms are located anywhere in the intracranial arteries, perhaps most frequently in the posterior circulation, 6~ but the giant and large aneurysms occur in less common sites such as cavernous sinus, anterior carotid and ophthalmic junction, or petrous region. 61 The most frequent locations are the basilar tip, the anterior commu-

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nicating, the posterior communicating, the posterior cerebral, the carotid periophthalmic, the vertebrobasilar junction, the superior cerebellar, and the middle cerebral bifurcation. 6~ Subarachnoid hemorrhage is a major cause of morbidity and mortality caused by intracranial aneurysms. Conventional arteriography and especially MRA demonstrate the presence of the aneurysms, the precise location, size, type of the aneurysm, and the size of its neck (Fig 11). Familial lipoprotein (a) has been implicated as an independent risk factor for atherosclerosis and a potential biological marker for unruptured intracranial aneurysms in adults. 62"6~ Favorable outcome is achieved in only 50% of cases, and the mortality rate is a devastating 3 0 % . 64 Adverse intraoperative events contribute significantly to instances of morbidity and mortality in most surgical series on ruptured intracranial aneurysms. 65"66Intraoperative complications occur in 30% of procedures. 67 During the initial 48 hours, after subarachnoid hemorrhage, patients who are explored carry a 6% to 10% risk of disastrous rebleeding with high mortality rates. 6s The therapeutic procedures are tailored to the location, the size, the time since the intracranial hemorrhage, the competence of the surgeon, and to other several circumstances mainly related to the state and stability of the patients. The most important factors that determine the patients's clinical outcome are brain damage from the primary hemorrhage, aneurysmal rebleeding, and delayed cerebral inchemia related to arterial vasospasm and hydrocephalus. 6~ Intraoperative complications and mortality a r e e l e v a t e d , 6~ but the literature shows a favorable response to emergency surgical clippling of the aneurysms, due to the significant mortality and morbidity rates from aneurysms rebleeding and a delayed cerebral ischemia caused by vasospasm that occurs during the waiting period. Other treatments mostly consist of endovascular procedures attempting to obliterate the aneurysms. These types of endovascular treatments are difficult even when performed by expert neuroradiologists. The literature reports several methods that include the use of detachable balloons, pushable microcoils, liquid embolic agents, Guglielmi detachable coil, 6~ a combination of metallic stent with a liquid polymer injection, 61 and others. The results with the different types of treatment are

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encouraging but not completely satisfactory. The administration of a calcium antagonist, mostly nimodipine, with surgical or the interventionist neuroradiological procedures, is common. However, treatment of intracranial aneurysms still constitutes a challange. CEREBROVASCULAR ANOMALIES The existence of intracranial vascular malformations (VMs) is known for almost a century, v~ The first histopathologic classification of VMs was presented by McCormick in 1966, 71 who modified the classification in 1984. 72 In this classification, McCormick divided VMs into four groups: (1) Arteriovenous malformations (AVMs), (2) cavernous malformations (CMs), (3) venous angiomas (VAs), and (4) capillary telangiectasia. Other rarer types of VMs are "mixed" vascular malformations of the brain that show distinct clinical, radiologic and pathologic profiles. 73-75 Other modified classifications of central nervous system (CNS) VMs based on a combination of location, morphology, and etiology have been presented. 76 VMs are dynamic lesions in which angiogenesis appears to take place constantly. During recent years, different groups report interesting papers in which it is possible to connect the findings of immunochemical investigations, especially growth factors and extracellular proteins, with traditional concepts related to the histology of intracranial V M s . 77-81

Arteriovenous malformations Arteriovenous malformation (AVM) is defined as a direct communication between one or more arteries and one or more draining veins without the intervention of a capillary b e d . 71'72"76 Direct shunting of blood is associated with increased blood flow, great distention of the involved arteries, and duplication or destruction of the elastica, fibrosis of the media, and focal thinning of the wall. The involved veins also show distention, tortuosity, and secondary changes in its walls. The most morbid and frequent presentation of AVM is cerebral hemorrhage, which occurs in about 60% of cases. 82 Deletereous effects of AVM on brain function include several pathologic symptoms, including headache, hydrocephalus, a loud bruit over the head, nausea or vomiting, neurological deficits, seizures, disturbances in consciousness, mass effects, or even sudden death. 82

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The existence of intracranial AVM is discovered more often in adults than in children, and they may be found anywhere in the intracranial spaces, intraparenchimatous, or meningeal or combined, either supratentorially or infratentorially. AVM may appear as an isolated pathology or associated with other diseases. 83 Vascular morphogenesis in embryos is a two-stage process. In the first stage (vasculogenesis), angioblasts differentiate into endothelial cells to form a primary vascular plexus. In the second stage (angiogenesis), the primary plexus undergoes remodeling and reorganization, including the accumulation of parieto-endothelial support cells. 78 The molecular mechanisms involved in the genesis and maintenance of AVM have not been elucidated, sa Studies carried out in recent years reveal that endothelial cell-specific protein tyrosine kinase receptor mediate various facets of blood vessel formation during vasculogenesis and vascular response to injury and disease states. 84 Vascular endothelial growth factors--the tyrosine kinases Fit-1 and Flk-l--and angiopoietins and their receptors appear to be necessary for angiogenesis and for proliferation, migration, adhesion, and tube formation. 79'85-9~ A newly discovered group of cytokines, and their receptors--Tie-1 and Tie-2-play a major role at later stages of vascular development, mediating endothelial cell matrix interactions that are essential to vascular maturation and remodeling, s6"91'92AVM and cavernous malformations show differences in their expression of endothelial cell angiogenesis receptors and of structural proteins. 84,93 The involved vessels in AVMs may show calcification and spontaneous occlusion. 94 AVM size can range from small or even microscopic to giant, involving a large part of an entire hemisphere. Most visible AVMs are pyramidal-shaped lesions with the apex toward the center of the brain and the base in the meninges. 76 Conventional arteriography or MRA show the AVM with the arterial feeders and draining veins (Fig 12). Usually there are less than three or four sizable feeders, but multiple small feeders occasionally are seen. The dilated draining veins connect the AVM to a nearby dural venous sinus. Enhancing the study with gadolinium may be necessary in some cases, especially in small AVM that may be missed by angiography, some of these by CT examination as w e l l . 76

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after 25 years. 99 Pregnant women with bleeding AVMs have a much greater risk of rebleeding during the same pregnancy, l~176 especially between the 15th and 20th weeks of gestation. 76

Venous angiomas

Fig 12. The coronal view of the three-dimensional MRA discloses an AVM in the territory of the left middle cerebral artery. The study shows a large "nidus" and a wide draining vein (asterisk).

The radiologic features of the parenchymal AVM consist of the presence of a mass of tangled vessels in the center of the malformation that is often known as the "nidus." Some AVMs show a simple fistulous connection without a nidus. Given that AVMs have a surgical or embolization treatment, it is necessary to grade AVMs radiologically based on size, location, number of major intracranial arteries supplying the feeders, age of the patient, and clinical state, to define the most effective and less dangerous treatment. Many of the deep AVMs are considered inoperable. Embolization and proton beam radiation have less risks than surgery. Gamma knife radiosurgery appears to hold some promise in the treatment of deep-seated AVMs, 95 but a size greater than 3 cm is a contraindication to its application. Embolization, mostly used preoperatively, is the preferred method of treatment in pediatric patients with multiple AVMs. However, there are cases of AVM in which preoperative embolization does not achieve sufficient occlusion of some arterial feeders to ensure control of intraoperative bleeding and resection of the AVM becomes necessary. In these cases, the use of low-flow deep hypothermic cardiopulmonary bypass may be required to control intraoperative bleeding. 96-98 Ten percent of patients with AVM die with the first hemorrhage, and another 10% die with the second. Series of long-term follow-up, report only 20% of patients alive and intact neurologically

Venous angiomas (VAs) consist of one or more dilated veins and their tributaries. No arteries appear in the lesion. VAs were thought to be rare before the introduction of MRA, but actually they may be the most common incidental vascular malformation detected by neuroradiologic studies, 1~ especially if contrast enhancing is used. Its clinical significance seems very low. Microscopically, VAs show modified structure of the veins, with the walls tending to be thicker and the lumens larger than those of normal veins. Images of VAs show a system of convergent small veins (the medusa head) terminating in one large control vein that empties into a meningeal or subependymal vein directly or through still larger veins. The smaller veins of a VA may appear no different from a capillary telangiectasis, especially if the draining vein is not seen. Despite being congenital, VA rarely are diagnosed in infancy. 33 They can be found in any part of the brain, l~ Given its nonneoplastic nature, they are considered as a type of venous developmental anomaly, 1~ and it is believed that they may represent a primary dysplasia of capillary and small veins. 1~ Although VAs can be seen by MR in T e, MR in T 1 with contrast enhancement may better demonstrate the malformation, and even better precision if MRA is performed. Very few patients with VAs require any type of treatment.

Capillary telangiectases Telangiectasis means a single lesion composed of multiple dilated capillaries. Capillary telangiectases are usually small (less than 2 cm), and they can occur in any part of the brain or in the spinal cord. They are frequent incidental findings at autopsy, especially in the pons. Microscopically, they show enlarged thin-walled, capillary-like vessels with red cells in the lumen. The exact nature of the capillary telangiectases is uncertain. The question of whether the involved vessels are true capillaries or simply dilated venules is still to be elucidated. 76 Histopathologic distinction between telangiectasia and hemangiomasta include not only the size and

CONGENITAL VASCULAR MALFORMATIONS IN CHILDHOOD

265

structure of the vascular channels, but the presence of normal neural tissue between the vessels of telangiectasia and gliotic brain without neurons between hemangiomatous vessels.

Vein of Galen malformations Vein of Galen malformations (VGMs) or vein of Galen aneurysmal malformations (VGAMs) are recognized as rare congenital abnormalities that can cause severe morbidity and mortality in neonates and less commonly in infants and older children. 1~ VGMs were described by Steinheil in 1895,1~ but this AVM was generally known only after the paper by Jaeger et al 1937. l~ In 1987, only 245 cases had been reported in the English literature. 105 Neonates usually present with high-output cardiac failure, which is often fatal despite medical management.I~176 Children usually present with heart failure, developmental delay, hydrocephalus, and seizures. Prenatal symptoms are common. Hydrocephalus with increased head circumference and Parinaud syndrome (impossibility to elevate the eyes) are caused by pressure of the VGAM on the prequadrigeminal pretectal zone. Mortality in the neonatal period is high. 105 Ultrasound studies may be useful during prenatal periods, 112 perinatal periods, 113"114 and at any age before the closure of the anterior fontanelle, ll5 and also assist the transtorcular embolization. It is useful in the follow-up of patients after the treatment. 113 CT, conventional arteriography, transcranial sonography with color Doppler (which can quantitate the blood flow velocity and size the aneurysm, and provide a useful baseline for follow-up) and especially MRA (Fig 13) that allows the classification of VGAMs through a complete exposition of the major vessels of supply, tortuosity of arterial access, venous system, and parenchymal and ventricular status. The knowledge of all these features without making the patient suffer, mostly a neonate, minimizes the duration of the diagnostic procedure and aids in early endovascular intervention. 116 Antenatal diagnosis has been reported after transcranial sonography and fetal MR studies, 112"117'118 and it has been associated with improved outcomes in survivors. 119 Several proposed classifications have been used to describe VGMs. 118'120"121 Lasjaunias et a1119"120"122 have proposed that VGMs be classified into two distinct

B Fig 13. (A and B) The three-dimensional MRA in sagittal and axial views shows a choroidal VGM with abundant blood supply that comes from the territories of both carotid (small asterisk) and the basilar (large asterisk) systems.

types: choroidal and mural. Choroidal VGMs usually seen in the neonatal period because of cardiac failure, abundant and usually bilateral blood supply from choroidal arteries and pericallosal arteries; many cases also show an additional supply from transdiencephalic or transmesencephalic perforating vessels (usually thalamoperforating arteries). 110,122 Occasionally, the middle cerebral artery may supply VGMs, but more likely in neonates than in older children. 116'12~ Mural-type VGMs receive their arterial supply from the collicular and posterior choroidal arteries that may be unilateral or bilateral and drain into the median prosencephalic vein and then to the dural sinuses. Clinically, mural-type VGMs present in infants with macrocephaly or failure to thrive and who have mild cardiac symptoms. 1o9.111,122

266

General theories on the possible cause of VGMs have been proposed. We can summarize some of them. The vein of Galen could be dilatated because of an increase in arterial pressure, 123 or the vein of Galen could be a varix associated with an AVM 115; or VGMs may also represent an ectasia secondary an increased flow associated with the obstruction of a dural sinuses distal to the VGM. 124 The presence of a persistent falcine sinus and postulated development around the 10th intrauterine week, however, may indicate that the anomaly represents a persistent median prosencephalic vein of Markowski, with absent development of a normal vein of Galen. 12~ Causes of the neurological symptoms, apart from the direct pressure of the VGMs--obstructive hydrocephalus and elevated intracranial press u r e - a r e reduced cerebral perfusion secondary to venous hypertension and to absortion of a great part of the intracranial vascularization by the VGAM that may cause ischemic zones, and brain herniations. The treatment of VGMs passed from the surgical procedures to the interventional neuroradiological m a n a g e m e n t . 1~ Surgery offers little improvement, with fatal outcomes in 80% to 100% of cases] ~176 Results have improved with endovascular management in infants and children with any mural-type or choroidal-type of V G M s . 105'109"112'116'119"122'127"12s Several endovascular techniques have been described. Treatment in later infancy by the transarterial approach may be ideallll'122; but the transvenous route is found useful in the first week of life when there is urgent indication for treatment of the neonate. 116 Mortality is increased in the neonatal period if no treatment is offered. In some patients with persistent cardiac failure, multisystem failure can be prevented by urgent endovascular treatment.116 Transfemoral and transtorcular embolizations of the vein of Galen have been described using various approaches, catheters, and embolic agents. The circumstances of every patient with VGM must be analyzed before initiating the technique in order to elect the most convenient. The spontaneous thrombosis of a VGM is occasionally reported. 129.130 Intracranial cavernous malformations

Cavernos malformations (CMs) or cavernous angiomas are vascular anomalies consisting of endothelium-lined cavernous vessels filled with

PASCUAL-CASTROVIEJO AND PASCUAL-PASCUAL

blood at various stages of thrombosis and organization, separated by a collagenous stroma devoid of mature vessel wall elements. 7~ CMs were described by Virchow in 1863. TM CMs is a relatively common disease, especially after the development of contrast-enhanced CT and MR studies, but symptomatic disease is considerably less common. 132 CMs are most often found in young adults. Presentation of this disease in children may be between 2 0 % 133 and 2 5 % . 133 There are descriptions of CMs in newborns, 134'135 but most patients are older than 10 years. 136 They can occur anywhere in the CNS but are most common in the subcortical white matter, pons, cerebellum, and the external capsule region. ~37 Those located in the temporal lobe and elsewhere in the brain are causally related to intractable epilepsy that can be cured by surgery. Rare localization, such as cavernous sinus, intraventricular, and pontocerebellar zones, have also been described. 138 CMs occur in an estimated 0.45% to 0.9% of the population, 7~ with male and female patients equally affected. They commonly manifest as seizures, gross intracranial hemorrhage, and focal neurological deficits. Lesions are frequently multiple in the same patient and may behave aggressively with repetitive hemorrhages and cumulative disability, although they may remain quiescent for many years. Hemorrhagic risk and neurological disability may be related to several factors, such as lesion location, previous hemorrhage, age, gender, and state of reproductive cycle. The proportion of patients developing clinical symptoms is higher in the hereditary form than in sporadic form of CMs. Lasjaunias et a1139 divided CMs into two types, cavernomas (malformations into the CNS) and cavernous hemangiomas (true tumors with proliferative potentiality). Studies following the introduction of MR have emphasized the predominance of CMs among the larger of angiographically occult vascular malformations of the brain] 4~ Angiographic results are normal in most patients with C M s . 139"144 Computed tomography (CT) shows a well-circumscribed, nodular lesion of uniform or variegated mixed density with juxtaposition of calcifications, hemorrhage, and cystic components. 7~ Magnetic resonance (MR) study is the most sensitive diagnostic tool for the evaluation of C M s . 140-145 The lesion typically appears as a welldefined, lobulated lesion, with a central core of

CONGENITAL VASCULAR MALFORMATIONS IN CHILDHOOD

Fig 14. The coronal view of the three-dimensional MRA shows the image of the cavernous malformation (asterisk).

reticulated mixed signal surrounded by a rim of signal hypointensity. 7~ Repeated subclinical intralesional and perilesional hemorrhages lead to ferritin deposition secondary to erythrocyte breakdown and account for the typical ring of low T 2 signal around CMs. Areas of hyperintensity correspond to acute or subacute hemorrhages and different stages of thrombus organization. The presence of cysts most likely represent residua of previously expanded hemorrhagic caverns that have since involuted with thrombus organization and resolution. Despite the great variety of images in the MR studies and the possibility of differential diagnosis, other types of intracranial diseases included calcified neoplasms, thrombosed AVMs, inflammatory lesions, infectious and granulomatous diseases. Neuroradiologists usually have few doubts in diagnosing CMs. MRA usually cannot demonstrate any lesion during arterial phases, but it shows the CMs during the venous system study (Fig 14). It is not rare to find a lesion near the region where another CM had been removed some time earlier in a patient who seeks consultation because of signs of a lesion in another part of the brain (Fig 15). CMs may be found as a sporadic and unique lesion or manifested as multiple lesions with familiar presentation in an autosomal-dominant inheritance associated with a great variety of mutations in the chromosome 7q11.2-21.146'148 This evidence was derived from the investigation of a large Hispanic American familyJ 46 The study of

267

other families showed that all Hispanic American families were linked to chromosome 7 and shared a common haplotype, which suggested that they had a c o m m o n a n c e s t o r . 147"149 Analysis of other North American and European (French, Spanish, and Portuguese) families demonstrated that some of these families were not linked to chromosome 7, which established genetic heterogeneity. ~5~ Mutations in the gene encoding krit 1 have recently been found as the cause of this hereditary type of CMs. j56-15s Lucas et al t53 documented a de novo germline mutation in krit 1 gene that caused cerebral CMs. Neuroimaging penetrance of CMs is much higher than clinical penetrance, and a great part of sporadic cases with multiple lesions are, in fact, familial cases. 151 The dynamic nature of CMs is well documented. 136"159-~6~ Growth of lesions and imaging changes have been reported in more than one third of patients. 137A6~ New lesions, with an average rate of 0.4 new lesions per patient per year, have been reported in 29% of the patients with familial CMs after a follow-up of a few years. 160 The management strategies are most influenced by the symptoms. Asymptomatic patients with single or multiple lesions may not require any urgent treatment but a watchful attitude with periodic re-imaging. Epilepsy, mostly caused by CMs in a

Fig 15. The MR study in coronal view reveals a bleeding CM in the brainstem and cerebellum (small arrowhead), and another CM in the right cerebral hemisphere (large arrowhead) close to a region where another CM was removed some time before.

268

PASCUAL-CASTROVlEJO AND PASCUAL-PASCUAL

sulcus. 166 The size of this vein is directly related with the extent of the cortical malformation, and may denote its severety. This vein may correspond to the primitive sylvian vein, which follows the fetal sylvian fissure, similar to those observed in the normal fetus of 20 and 26 weeks' gestation. 167 This implies that at this time there is an arrest in cortical development in the affected region, including the venous maturation.

Vascular malformations of the meninges Vascular malformations can be found in the leptomeninges, in the dura, and in the venous sinuses.

Vascular malformations of the leptomeninges. Fig 16. Sturge-Weber syndrome. The MR enhanced with gadolinium shows leptomeningeal angiomatosis and the choroidal angiomatosis (arrow).

temporal lobe, should be treated with anticonvulsant medication, at least during the time that the seizures respond to the medication. However, surgical resection of the lesion is necessary for cases with intractable epilepsy, and the results usually are satisfactory with seizure control in most cases if the resection of the CM is complete. 137A41A62 Favorable results have also been reported in the resection of accessible symptomatic supratentorial lesions, in brainstem lesions that appear at the pial or ventricular surfaces. 137"141"162'163 There is no consensus as to whether the excision of these lesions should be performed after an initial bleed or should await recurrence of symptoms or progression. 7~ There is evidence to suggest the novo lesion genesis in certain patients. 164 The morbidity and mortality risks in surgery for brain lesions are high. Radiosurgical treatment of CMs is controversial. The use of standard doses gives a poor clinical response and a high rate of complications. Lower margin doses are used, preferably for deep and inoperable CMs, and may provide more promising results. ~65

The most frequent is observed associated is with Sturge-Weber syndrome (SWS). The lesions can be located to any zone of the leptomeninges over the hemisphere ipsilateral to the facial nevus flammeus affecting the area innervated by the first sensory branch of the trigeminal nerve. Only 23% of patients with bilateral facial nevus flammeus show bilateral leptomeningeal angiomatosis. 168 The enhancement of MR with Gadolinium became

~i!i!

!i

Cortical venous anomalies /

Intracranial venous anomalies of the cortical areas usually consist of abnormal drainage, mostly associated with anomalies of neuroblast migration. They usually correspond to persistence of a cortical vein that drains the blood into the superior sagittal sinus after following the primitive sylvian

Fig 17. The sagittal view of the MRA study shows the sinus pericranii (arrows) in a 3-day-old neonate.

CONGENITAL VASCULAR MALFORMATIONS IN CHILDHOOD

an obligatory study in these patients because it not only demonstrates the leptomeningeal lesions but also the ocular choroidal angiomas (Fig 16). Only patients with nevus flameus affecting the upper eyelid show the choroidal angiomas, mostly associated with glaucoma. Dural arterionenous malformations. Clinical behavior and morphology of the dural AVM is similar to the cerebral parenchymal examples. Common clinical findings include repeated headaches or subarachnoid or subdural hemorrhages. The enlarged, tortuous veins and the dural sinus are always more prominent than the arterial feeders. Multiple dural AVMs have been reported in children. 169 The venous sinuses rarely show lacunar enlargement. It occurs locally and at most times in a lateral sinus. The local enlargement of the sinus usually is the final part of an AVM. 17~ We studied a case with a giant dilatation of a lateral sinus and a medium-sized dilatation of the other lateral sinus associated with an ipsilateral facial hymphangioma.~7a The treatment and prognosis of these lesions depend on the clinical symptoms and the size. Small lesions usually are asymptomatic and mostly do not need treatment. Those of me-

269

dium sizes may be treated either by surgery or ablated by intravascular injection of thrombotic agents. Large AVMs are treated mostly by surgery. Aneurysmatic dilatation of the torcula. This is a very rare malformation when it is a primary dilatation. 173 Most times this anomaly is a secondary dilatation associated with vein of Galen malformation. Clinical alterations consist of bilateral exophthalmus facial edema and psychomotor involution. Angiographic studies show generalised dilatation of the venous system including the t6rcula.

Sinus pericranii. This is a rare congenital anomaly of the dyploic veins that consists in the enlargement of the extracranial nonmuscular venous vessels, which communicate directly with an intracranial venous sinus. 174 When the head is in a low position, the blood passes from the sinus to the extracranial diploic veins and its stasis causes a bulk effect that disappears with directly applied pressure. The vascular malformation may appear in the neonatal period or during the first years. MRA in sagittal view best demonstrates the sinus pericranii (Fig 17). The treatment of this anomaly consists of surgical resection of the lesion. 175

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