Intramedullary spinal arteriovenous malformation in a boy of familial cerebral cavernous hemangioma
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- Hu, M., Wu, C., Lin, K. et al. Childs Nerv Syst (2008) 24: 393. doi:10.1007/s00381-007-0536-x
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The coexistence of spinal arteriovenous malformation (AVM) and a familial cerebral cavernous hemangioma (CCH) is extremely rare.
A 9-year-old boy suddenly developed severe paraplegia and urinary dysfunction. Spinal magnetic resonance imaging (MRI) scan revealed a cervical and upper thoracic intramedullary lesion. Due to acute neurological dysfunction, the patient underwent emergency surgical exploration. An intramedullary vascular lesion was found and excised. Pathologically, AVM was noted. After the surgery, the boy was ambulatory with left lower limb stiffness. MRI scan of the brain revealed multiple cerebral cavernous hemangioma. Symptomatic multiple CCH in his mother and grandmother were also noted.
We concluded that the presence of spinal AVM should be suspected if the patient with familial CCH develops the signs of space-occupying lesion of the spinal cord, facilitating early diagnosis of the spinal AVM.
KeywordsArteriovenous malformationCavernous hemangiomaSpineCerebralGeneticChild
Spinal arteriovenous malformations (AVMs) are vascular abnormalities within the spinal cord that were present at birth. Their incidence ranges from 0.3% to 4.9% in all patients having AVM. In 1992, Anson and Spetzler classified spinal cord vascular malformations into four categories . Our case presented as type II intramedullary AVM which is a true intramedullary or glomus-type malformation and occurs within the substance of the spinal cord . These lesions usually present in young patients with acute neurologic deterioration secondary to their location, which is usually the dorsal cervicomedullary region. These are important clinical entities because they produce considerable morbidity and may even be fatal if left untreated [2, 12].
Cerebral cavernous hemangioma (CCH) is also rare. The incidence in the general population is estimated to be 0.5% . CCH can occur as sporadic or inherited conditions . Spinal AVMs have been associated with multiple cerebral AVMs  or inherited clinical syndromes such as familial cutaneous hemangiomas  and pulmonary AVMs ; but there have been no reports that associate with familial CCH. In this paper, we report a case of spinal AVM in a boy with familial CCH, who was successfully treated with resection of the vascular lesions. The pathogenesis, hereditary and genetic basis of this entity, is discussed.
A 9-year-old boy was admitted to hospital because he had been complaining of back pain and bilateral arm soreness since 4 days before admission. Two days prior to his admission, the patient had bilateral lower extremity weakness, bilateral numbness of the feet, and urine incontinence. On the day of admission, numbness progressed from the distal to the proximal lower extremities and accompanied with weakness and paraplegia. He had been healthy and his past medical history was unremarkable.
Type II intramedullary AVM was surgically and pathologically diagnosed in this patient. AVMs and cerebral cavernous malformations (CCMs) are generally regarded as a form of vascular malformation. AVMs lack capillary beds and manifest apoplectic bleeding under high-flow conditions, whereas CCMs exhibit an immature vessel wall, a brittle hemorrhagic tendency, and epileptogenesis. In contrast to CCM ultrastructure, AVM lesions maintain normal vessel wall and structural integrity with endothelial cell denudation. These pathological lesions likely involved abnormal assembly or maintenance of blood vessels, resulting in dysmorphic vessel phenotypes. Familial CCH disease is, in part, caused by mutations in a cytoskeletal-related protein which is integral to inter-endothelial cell connectivity and maturation of the vascular wall. Rare familial forms of AVM disease have been correlated with two different transforming growth factor-β receptor components, possibly causing disturbance in signaling during vascular assembly . Seker et al. revealed an expression of integrins both in cerebral AVM and cavernous malformations . They concluded that if one accepted the premise that immunohistochemistry had inherent methodological problems, integrins alpha-beta1, alpha-beta3, and alpha-beta5 may be expressed in AVMs and CCMs in different ways that may be linked to stages of angiogenic maturation. As a result, both of these diseases may have a genetic basis.
In clinical observation, most AVMs were sporadic, but some of them were genetically originated which developed during embryogenesis. A recent study identified an association with RASA1 mutations and AVMs . The phenotypic variability can be explained by the involvement of p120-RasGAP in signaling for various growth factor receptors that control proliferation, migration, and survival of several cell types, including vascular endothelial cells .
CCH can occur sporadically and in many familial cases. These cases exhibited an autosomal dominant pattern of inheritance and seemed to affect the Hispanic population . Recent research has demonstrated at least three separate genes related to the familial form of the disease. The first gene is located at band 7q11.2-q21 . The second gene is located at band 7p15-p13 and controls the production of a protein named malcavernin . The third gene is on chromosome 3 at band 3q . Research is ongoing to further delineate the function of this gene and its relationship to cavernous angiomas.
As in this case, intramedullary AVMs generally present at a much earlier age. The clinical course of these lesions is marked by progressive and fluctuating myelopathy, often overlaid by periods of acute neurologic deterioration secondary to hemorrhage within the AVM. Sudden apoplectic presentation, often with profound neurologic impairment and possible transverse myelopathy, is common in spinal AVMs.
Treatment of intramedullary spinal AVMs involves initial embolization of feeding vessels using particulate matter. Immediate clinical improvement is often noted after embolization, through reduction in arterial steal and improved cord perfusion. However, in our case, due to rapid deterioration of spinal cord function, pre-operative angiography was not performed and emergent surgical exploration and decompression was done. Surgical intervention is associated with a mortality of 0–5%, with neurological deterioration occurring in 7–20% and residual AVM being present on follow-ups in 23–41% of cases . We recommend to perform chromosomal analysis in the patient with familial CCH and to check the spinal MRI scan of the patient with genetic tendency for a neurological sign to facilitate early diagnosis of the spinal AVM, and good outcome can be expected after prompt surgical intervention.
This study reports the association of two kinds of vascular malformation of spinal AVM and familial CCH which has not been previously reported. However, the issue of etiology may be heredity. Further studies concerning the possible relation of a genetic component to the pathogenesis of these two diseases should be investigated. Our report implicated that some individuals may be genetically predisposed to develop more than one of these vascular lesions.