01_05_JNS.2 12/15/04 2:37 PM Page 156 J Neurosurg 102:156–160, 2005 Cerebellopontomandibular vascular malformation: a rare type of cerebrofacial arteriovenous metameric syndrome Case report HYUN-SEUNG KANG, M.D., MOON HEE HAN, M.D., BAE JU KWON, M.D., BYUNG-WOO YOON, M.D., AND KEE-HYUN CHANG, M.D. Departments of Radiology and Neurology, Seoul National University College of Medicine; Clinical Research Institute, Seoul National University Hospital; and Institute of Radiation Medicine, SNUMRC, Seoul, Korea √ The concept of a cerebrofacial arteriovenous metameric syndrome (CAMS) recently has been posited. A 22-year-old woman presented with gait ataxia. She had unilateral angiomatous lesions involving the lower face, the auricle, and the retromastoid area, as well as the tongue on the right side. Angiography revealed the presence of extensive arteriovenous malformations (AVMs) in the ipsilateral cerebellum and pons, in addition to those located in the facial region. The authors report a case of multiple AVMs of the face, cerebellum, and pons, corresponding to CAMS Type 3, and include a review of the literature. KEY WORDS • neurocutaneous syndrome • vascular malformation History. This 22-year-old woman was admitted for an evaluation of gait ataxia. At birth an angiomatous lesion was present on the lower right side of her face, and when she was 14 years old she was found to be deaf in the right ear. Examination. The patient presented with progressive gait ataxia that had developed insidiously over a 3-year period. She had normal intelligence. No family members were reported to have a similar cranial or cerebral vascular lesion. A neurological examination disclosed a full range of extraocular muscle movement with gaze-evoked nystagmus in horizontal directions, slightly decreased deep tendon reflexes, and dysdiadochokinesia on her right side. Fundoscopy and fluorescein angiography revealed a normal retinal vasculature. Intraocular pressure was noted to be 10 mm Hg on both sides. The patient’s brainstem auditory evoked response did not demonstrate any wave peaks on the right side. A reddish-purple skin discoloration was observed in the mandibular angle, preauricular, auricular, and retromastoid areas, and on the anterior part of the tongue on the right side (Fig. 1). The skin lesion was soft, swollen, and nonpulsatile. Magnetic resonance imaging revealed diffuse vascular signal voids throughout the entire cerebellar hemisphere, vermis, and pons on the right side (Fig. 1). There was no evidence of hemorrhage and no supratentorial lesion was observed. Angiography revealed facial, cerebellar, and pontine AVMs on the right side (Fig. 2). Diagnosis and Observation. Given the physical and neuroimaging findings in this case and following a thorough review of the appropriate literature, we made a diagnosis of CAMS Type 3. In view of this woman’s mild clinical symptoms despite the extensiveness of the vascular malformations, an expectant approach was chosen. The patient is being followed up periodically. Abbreviations used in this paper: AVM = arteriovenous malformation; CAMS = cerebrofacial arteriovenous metameric syndrome; WMS = Wyburn-Mason syndrome. Discussion Angiodysplasia consists of angiomatous lesions caused VARIETY of neurocutaneous vascular lesions or syndromes have been reported; however, sometimes a particular syndromic malformation is hard to classify as a specific entity. Cerebrofacial arteriovenous metameric syndrome is a newly devised concept.2 It encompasses complex vascular malformations that have a metameric distribution in the craniofacial region, and three subtypes have been postulated. Although several authors have reported on distinctive groups of vascular malformations, referred to as unilateral retinocephalic vascular malformation, WBS, or Bonnet-Dechaume-Blanc syndrome, most of these lesions belong to CAMS Types 1 and 2 and display a prosencephalic distribution. In contrast, CAMS Type 3, also known as the rhombencephalic lesion, has rarely been described.24 The authors report a case of multiple vascular malformations of the face, cerebellum, and pons, corresponding to CAMS Type 3, and review the literature about this syndrome. A Case Report 156 J. Neurosurg. / Volume 102 / January, 2005 01_05_JNS.2 12/15/04 2:37 PM Page 157 Cerebellopontomandibular vascular malformation FIG. 1. Upper Left: Photograph of the patient’s face showing skin discoloration in the mandibular angle, auricle, and retromastoid areas. Magnetic resonance images demonstrating a massive AVM. In the right side of the posterior fossa, a huge lesion involving the cerebellar hemisphere and the brainstem is shown on an axial T2-weighted axial image (upper right) and on Gd-enhanced T1-weighted sagittal (lower left) and coronal (lower right) images. by a faulty embryogenesis of the vascular wall.10 Huber10 classified these lesions into three types: 1) diffuse angiomatous phacomatoses; 2) regional angiomatous phacomatoses; and 3) nonangiomatous phacomatoses. The first group includes hereditary hemorrhagic telangiectasia or RenduOsler-Weber syndrome, blue rubber bleb nevus syndrome, Mafucci syndrome, Bailey glomangiomatosis, and ataxia telangiectasia or Louis–Bar syndrome. The second group includes encephalofacial angiomatosis or Sturge–Weber J. Neurosurg. / Volume 102 / January, 2005 syndrome, WMS or Bonnet-Dechaume-Blanc syndrome, meningocerebral angiomatosis or Divry–van Bogaert disease, cutaneous meningomedullary angiomatosis or Cobb syndrome, congenital venous dysplasia or Klippel-Trenaunay-Weber syndrome, and von Hippel–Lindau disease. Taking another point of view, these lesions can be divided into arterial, capillary, capillary–venous, venous, lymphatic, and venolymphatic malformations, depending on which channel components are involved (Table 1).6,14 These 157 01_05_JNS.2 12/15/04 2:37 PM Page 158 H. S. Kang, et al. FIG. 2. Angiograms of the lesion. Following an external carotid artery injection, parts of the facial (arrow) and intracranial lesions appear opacified in both anteroposterior (upper left) and lateral (upper right) views. The anterior pontomesencephalic vein, a draining vein of the posterior fossa AVM, can be seen (arrowheads in upper right). The superior portion of the huge pontocerebellar AVM is opacified in response to the left vertebral artery injection in both the anteroposterior (lower left) and lateral (lower right) views. Enlarged pontine perforating arteries are distinctive in the lateral view (lower left). The inferior portion of the AVM is opacified by the right vertebral artery injection (data not shown). classifications confound a systemic arrangement, however, and some syndromic neurocutaneous vascular malformations may not fit specific diagnoses. It is known that Brock and Dyke first documented the combination of retinal, optic nerve, chiasmal, midbrain, and cerebellar involvement by an AVM in 1932.18 After another description of two cases with racemose angioma in the ipsilateral retina, orbit, and face by Bonnet, et al., in 1937, and 158 an extensive review by Wyburn-Mason,25 various names have been given to this condition historically, as summarized by Gibo, et al. (Table 2).9 The characteristic features of WMS include cutaneous vascular nevi and ipsilateral cerebral AVMs involving the visual pathways from the occipital lobes and thalamus via the hypothalamus, optic chiasm, and optic nerve to the retina.25 Typically WMS is composed of unilateral retinoJ. Neurosurg. / Volume 102 / January, 2005 01_05_JNS.2 12/15/04 2:37 PM Page 159 Cerebellopontomandibular vascular malformation TABLE 1 Syndromic vascular malformations and the channel components involved* TABLE 2 Various names related to CAMS* Authors & Year Syndrome Channel Components Involved Sturge–Weber Turner/Noonan blue rubber bleb nevus Maffucci Klippel–Trenaunay Parkes–Weber Bonnet-Dechaume-Blanc or Wyburn-Mason Rendu-Osler-Weber or HHT capillary venous† or venolymphatic‡ lymphatic† venous† venous† capillary lymphaticovenous† capillary venous† capillary venous‡ venous‡ * HHT = hereditary hemorrhagic telangiectasia. † According to Burrows. ‡ According to Luo, et al. Bonnet, et al., 1937 Wyburn-Mason, 1943 Fishgold, et al., 1952 Paillas, et al., 1959 Bufford, et al., 1963 Rubinstein, 1972 Theron, et al., 1974 Troost, et al., 1978 Morgan, et al., 1985 Names retinal cirsoid aneurysm associated w/ facial & cerebral AVMs arteriovenous aneurysm of midbrain & retina & facial naevi neuro-retinal angiomatosis encephalo-retino-facial angiomatosis retino-optico-mesencephalic aneurysm syndrome mesencephalo-oculo-facial angiomatosis unilateral retinocephalic vascular malformation racemose hemangioma of retina, thalamus, & midbrain ophthalmofacial–hypothalamic AVM * Modified from Gibo, et al. cephalic vascular malformations,22 although some authors of case reports have described bilateral lesions,11,15,19 and asserted the nonuniversality of retinal involvement.2,5,9,20 Patients present with a combination of symptoms related to cosmetic and psychological problems, life-threatening epistaxis or gingival bleeding, blindness, or cerebral hemorrhage.20 Midbrain or cerebellar involvement has only been rarely described.21,22 It is not easy to explain the pathogenesis of this sort of complex vascular malformation composed of intracranial and extracranial lesions. Ponce and associates20 suggested that a “unilateral dysgenesis of the anterior primordial vascular plexus” was the pathogenetic mechanism of WMS. They also proposed that the syndrome’s broad spectrum of manifestation depends on the timing of an embryonic insult at 7 weeks of gestation, the period of optic cup closure, which would represent a critical point in the determination of the presence or absence of an eye and/or midbrain lesion. Although this explanation seems to be adequate to explain a typical case of WMS, it has its own limitation in explaining mandibulopontocerebellar lesions as shown in our case. A theory (and classification) based on the metamere seems to be more persuasive and inclusive.2 According to research on avian embryos in which the quail-chick chimera technique has been used, mesoderm and neural crest cells from a given transverse, or metameric, level occupy the same territory in the face and brain, and the two cell types also cooperate in myogenesis and vasculogenesis.1,7,8,13 During vasculogenesis, endothelial cells and the tunica media are derived from the mesoderm and neural crest cells, respectively. Moreover, interactions between Hox genes, neural crest cells, and the mesoderm are complex and involve multiple levels of regulation.23 This complexity may be the causative basis of various metameric vascular malformations. Based on these embryologic backgrounds, Bhattacharya and colleagues2 devised a classification scheme for metameric craniofacial vascular anomalies and reviewed 15 cases of WMS. These authors noted striking similarities between the distribution of lesions in cases of WMS and fate maps of neural crest cells and cephalic mesoderm in avian experiments. They suggested that CAMSs encompass vascular malformations with a metameric distribution in the craniofacial region and are categorized as CAMS 1, 2, and 3 according to the distribution of those lesions (Table 3). J. Neurosurg. / Volume 102 / January, 2005 The syndrome is nonhereditary and is believed to be caused by a somatic mutation in the neural crest or an adjacent cephalic mesoderm prior to migration.2,12 Interestingly, this scheme of arteriovenous metameric syndrome can be a continuum embodying CAMS 1, 2, and 3, as well as spinal arteriovenous metameric syndrome 1 to 31, commonly known as Cobb syndrome, along the entire craniocaudal axis. Whereas cases of CAMS 1 and 2 are relatively common, cases of CAMS 3 have been rarely reported.24 In a series reported by Bhattacharya and colleagues,2 the authors found no case with cerebellum, pons, and mandible involvement. Instead they cited a case reported by Theron, et al.22 Our case showed distinctively extensive lesions in the pons and cerebellum and included facial lesions, providing additional substantial evidence for the existence of CAMS 3. Our lack of knowledge of the natural history of this condition hampers management decisions in cases of this syndromic malformation. Occasionally, resection of the small opticohypothalmic AVM, with or without embolization, has been attempted and has produced satisfactory results.9,16 Embolization can be a treatment option in cases in which there is bleeding from facial lesions.4 Otherwise, in view of the risk of treatment, conservative management with careful follow-up review may be chosen.17 In a case of BonnetDechaume-Blanc syndrome there was evidence of spontaneous involution of a retinal and intracranial AVM.3 Many patients with CAMS are likely to present to isolated specialists in ophthalmology, otolaryngology, and plastic surgery and, therefore, the underlying and unifying condition may go unrecognized.22 A high index of suspicion is required in treating patients with a retinal or facial AVM, in which a systematic neuroimaging evaluation of metamerically related territories seems to be necessary. TABLE 3 Embryological origin and topographic projection of CAMS* Type Embryological Origin Topographic Projection CAMS 1 CAMS 2 medial prosencephalic lateral prosencephalic CAMS 3 lateral rhombencephalic hypothalamus, nose occipital lobe, thalamus, optic tract, retina, maxilla cerebellum, pons, mandible * According to Bhattacharya, et al. 159 01_05_JNS.2 12/15/04 2:37 PM Page 160 H. S. Kang, et al. References 1. Bergwerff M, Verbene ME, DeRuiter MC, Poelmann RE, Gittenberger-de Groot AC: Neural cell contribution to the developing circulatory system: implications for vascular morphology? Circ Res 82:221–231, 1998 2. Bhattacharya JJ, Luo CB, Suh DC, Alverez H, Rodesch G, Lasjaunias PL: Wyburn-Mason or Bonnet-Dechaume-Blanc as cerebrofacial arteriovenous metameric syndromes (CAMS). A new concept and a new classification. Intervent Neuroradiol 7:5–17, 2001 3. 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Luo CB, Bhattacharya JJ, Ferreira M, Alverez H, Rodesch G, Lasjaunias P: Cerebrofacial vascular disease. Orbit 22:89–102, 2003 15. Mello LR, Detoni XA: Bonnet-Dechaume-Blanc syndrome. Report of a case with bilateral arteriovenous malformations. Acta Radiol Suppl 347:187–192, 1976 16. Morgan MK, Johnston IH, de Silva M: Treatment of ophthalmofacial-hypothalamic arteriovenous malformation (BonnetDechaume-Blanc syndrome). Case report. J Neurosurg 63: 794–796, 1985 17. Muthukumar N, Sundaralingam MP: Retinocephalic vascular malformation: case report. Br J Neurosurg 12:458–460, 1998 18. Newton TH, Troost BT: Arteriovenous malformations and fistulae, in Newton TH, Potts DG (eds): Radiology of the Skull and Brain. Angiography, Vol 2, Book 4. St. Louis: CV Mosby, 1974, pp 2490–2565 19. Patel U, Gupta SC: Wyburn-Mason syndrome. A case report and review of the literature. Neuroradiology 31:544–546, 1990 20. Ponce FA, Han PP, Spetzler RF, Canady A, Feiz-Erfan I: Associated arteriovenous malformation of the orbit and brain: a case of Wyburn-Mason syndrome without retinal involvement. Case report. J Neurosurg 95:346–349, 2001 21. Tamaki N, Fujita K, Yamashita H: Multiple arteriovenous malformations involving the scalp, dura, retina, cerebrum and posterior fossa. Case report. J Neurosurg 34:95–98, 1971 22. Theron J, Newton TH, Hoyt WF: Unilateral retinocephalic vascular malformations. Neuroradiology 7:185–196, 1974 23. Trainor PA, Krumlauf R: Hox genes, neural crest cells and branchial arch patterning. Curr Opin Cell Biol 13:698–705, 2001 24. Wong IYC, Batista LL, Alvarez H, Lasjaunias PL: Craniofacial arteriovenous metameric syndrome (CAMS) 3—a transitional pattern between CAM 1 and 2 and spinal arteriovenous metameric syndromes. Neuroradiology 45:611–615, 2003 25. Wyburn-Mason R: Arteriovenous aneurysm of mid-brain and retina, facial naevi and mental changes. Brain 66:163–203, 1943 Manuscript received June 5, 2004. Accepted in final form September 8, 2004. Address reprint requests to: Moon Hee Han, M.D., Department of Diagnostic Radiology, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul 110–744, Korea. email: hanmh@ radcom.snu.ac.kr. J. Neurosurg. / Volume 102 / January, 2005