Biological activity of adult cavernous malformations: a study of 56 patients

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  • 1 Department of Neurosurgery, Philipps-University, Marburg, Germany; and Department of Neurology, University of Zürich, Switzerland
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Object. Cerebral cavernous malformations (CCMs) have previously been considered as congenital and biologically static malformations. On the other hand, the potential for growth and de novo generation of CCMs have also been reported. It is therefore important to study the proliferative and neoangiogenetic capacity of these lesions.

Methods. The authors studied the surgical specimens of 56 CCMs (23 deep and 33 superficial) obtained from adult patients. The proliferative activity of the endothelium and the neoangiogenetic capacity of these lesions were considered through immunohistochemical anaylsis of proliferating cell nuclear antigen (PCNA), MIB-1, Flk-1, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1α, and endoglin antibodies.

Positive immunostaining of endothelial cells occurred in 86% of patients for PCNA and in 38% of the cases for MIB-1. The expression of Flk-1 was observed in the endothelium of 71% of the cases, for VEGF in 41%, for HIF-1α in 48.1%, and for endoglin in 63.6% of the cases. The correlation of immunohistochemical and clinical data indicated that VEGF was expressed in significantly less deep-seated lesions when compared with superficial CCMs. Neither the expression of the proliferative markers nor the expression of the angiogenetic antibodies correlated with patient age at surgery, sex, or the number of recent prior hemorrhagic episodes in the patients.

Conclusions. The CCMs from adult patients are active lesions exhibiting endothelial proliferation and neoangiogenesis. According to the data in this study, neoangiogenesis is more prominent in superficial CCMs than in deep-seated CCMs and is not associated with recent prior hemorrhages.

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Contributor Notes

Address reprint requests to: Ulrich Sure, M.D., Department of Neurosurgery, Philipps-University, Baldingerstrasse, 35033 Marburg, Germany. email: sure@med.uni-marburg.de.
  • 1.

    Aiba T, , Tanaka R, , Koike T, , Kameyama S, , Takeda N, & Komata T: Natural history of intracranial cavernous malformations. J Neurosurg 83:5659, 1995 Aiba T, Tanaka R, Koike T, Kameyama S, Takeda N, Komata T: Natural history of intracranial cavernous malformations. J Neurosurg 83:56–59, 1995

    • Search Google Scholar
    • Export Citation
  • 2.

    Altman DG: Practical Statistics for Medical Research. Boca Raton: Chapman & Hall CRC, 1991 Altman DG: Practical Statistics for Medical Research. Boca Raton: Chapman & Hall CRC, 1991

    • Search Google Scholar
    • Export Citation
  • 3.

    Awad IA, , Robinson JR Jr, , Mohanty S, & Estes ML: Mixed vascular malformations of the brain: clinical and pathogenetic considerations. Neurosurgery 33:179188, 1993 Awad IA, Robinson JR Jr, Mohanty S, Estes ML: Mixed vascular malformations of the brain: clinical and pathogenetic considerations. Neurosurgery 33:179–188, 1993

    • Search Google Scholar
    • Export Citation
  • 4.

    Bertalanffy H, , Benes L, , Miyazawa T, , Alberti O, , Siegel AM, & Sure U: Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated patients. Neurosurg Rev 25:155, 2002 Bertalanffy H, Benes L, Miyazawa T, Alberti O, Siegel AM, Sure U: Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated patients. Neurosurg Rev 25:1–55, 2002

    • Search Google Scholar
    • Export Citation
  • 5.

    Bertalanffy H, , Gilsbach JM, , Eggert HR, & Seeger W: Microsurgery of deep-seated cavernous angiomas: report of 26 cases. Acta Neurochir 108:9199, 1991 Bertalanffy H, Gilsbach JM, Eggert HR, Seeger W: Microsurgery of deep-seated cavernous angiomas: report of 26 cases. Acta Neurochir 108:91–99, 1991

    • Search Google Scholar
    • Export Citation
  • 6.

    Bertalanffy H, , Kühn G, , Scheremet R, & Seeger W: Indications for surgery and prognosis in patients with cerebral cavernous angiomas. Neurol Med Chir 32:659666, 1992 Bertalanffy H, Kühn G, Scheremet R, Seeger W: Indications for surgery and prognosis in patients with cerebral cavernous angiomas. Neurol Med Chir 32:659–666, 1992

    • Search Google Scholar
    • Export Citation
  • 7.

    Breier G, , Albrecht U, , Sterrer S, & Risau W: Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114:521532, 1992 Breier G, Albrecht U, Sterrer S, Risau W: Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114:521–532, 1992

    • Search Google Scholar
    • Export Citation
  • 8.

    Brunken M, , Sagehorn S, , Leppien A, , Muller-Jensen A, & Halves E: Neuformation eines Cavernoms bei begleitender, vorbestehender venoser Malformation unter immunsuppresiver Behandlung. Zentralbl Neurochir 60:8185, 1999 Brunken M, Sagehorn S, Leppien A, Muller-Jensen A, Halves E: Neuformation eines Cavernoms bei begleitender, vorbestehender venoser Malformation unter immunsuppresiver Behandlung. Zentralbl Neurochir 60:81–85, 1999

    • Search Google Scholar
    • Export Citation
  • 9.

    Comair Y, , LeBlanc R, & Robitaille Y: Effects of estrogen on cerebral arteriovenous malformations in vitro: towards a new paradigm. J Neurosurg 72:337A, 1990 (Abstract) Comair Y, LeBlanc R, Robitaille Y: Effects of estrogen on cerebral arteriovenous malformations in vitro: towards a new paradigm. J Neurosurg 72:337A, 1990 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 10.

    Davenport WJ, , Siegel AM, , Dichgans J, , Drigo P, , Mammi I, & Pereda P, et al: CCM1 gene mutations in families segregating cerebral cavernous malformations. Neurology 56:540543, 2001 Davenport WJ, Siegel AM, Dichgans J, Drigo P, Mammi I, Pereda P, et al: CCM1 gene mutations in families segregating cerebral cavernous malformations. Neurology 56:540–543, 2001

    • Search Google Scholar
    • Export Citation
  • 11.

    Del Curling O Jr, , Kelly DL Jr, , Elster AD, & Craven TE: An analysis of the natural history of cavernous angiomas. J Neurosurg 75:702708, 1991 Del Curling O Jr, Kelly DL Jr, Elster AD, Craven TE: An analysis of the natural history of cavernous angiomas. J Neurosurg 75:702–708, 1991

    • Search Google Scholar
    • Export Citation
  • 12.

    Detwiler PW, , Porter RW, , Zabramski JM, & Spetzler RF: De novo formation of a central nervous system cavernous malformation: implications for predicting risk of hemorrhage. Case report and review of the literature. J Neurosurg 87:629632, 1997 Detwiler PW, Porter RW, Zabramski JM, Spetzler RF: De novo formation of a central nervous system cavernous malformation: implications for predicting risk of hemorrhage. Case report and review of the literature. J Neurosurg 87:629–632, 1997

    • Search Google Scholar
    • Export Citation
  • 13.

    Detwiler PW, , Porter RW, , Zabramski JM, & Spetzler RF: Radiation-induced cavernous malformation. J Neurosurg 89:167169, 1998 Detwiler PW, Porter RW, Zabramski JM, Spetzler RF: Radiationinduced cavernous malformation. J Neurosurg 89:167–169, 1998

    • Search Google Scholar
    • Export Citation
  • 14.

    Dupre N, , Verlaan DJ, , Hand CK, , Laurent SB, , Turecki G, & Davenport J, et al: Linkage to the CCM2 locus and genetic heterogeneity in familial cerebral cavernous malformations. Can J Neurol Sci 30:122128, 2003 Dupre N, Verlaan DJ, Hand CK, Laurent SB, Turecki G, Davenport J, et al: Linkage to the CCM2 locus and genetic heterogeneity in familial cerebral cavernous malformations. Can J Neurol Sci 30:122–128, 2003

    • Search Google Scholar
    • Export Citation
  • 15.

    Fahlbusch R, & Strauss C: Zur chirurgischen Bedeutung von cavernösen Hämengiomen des Hirnstammes. Zentralbl Neurochir 52:2532, 1991 Fahlbusch R, Strauss C: Zur chirurgischen Bedeutung von cavernösen Hämengiomen des Hirnstammes. Zentralbl Neurochir 52:25–32, 1991

    • Search Google Scholar
    • Export Citation
  • 16.

    Fobe JL, , de Lima JB, , de Buone ML, & Correa Neto J: Angioma cavernoso familiar. Relato en tres geracoes. Arq Neuropsiquiatr 54:655660, 1996 Fobe JL, de Lima JB, de Buone ML, Correa Neto J: Angioma cavernoso familiar. Relato en tres geracoes. Arq Neuropsiquiatr 54:655–660, 1996

    • Search Google Scholar
    • Export Citation
  • 17.

    Heckl S, , Aschoff A, & Kunze S: Radiation-induced cavernous hemangiomas of the brain: a late effect predominantly in children. Cancer 94:32853291, 2002 Heckl S, Aschoff A, Kunze S: Radiation-induced cavernous hemangiomas of the brain: a late effect predominantly in children. Cancer 94:3285–3291, 2002

    • Search Google Scholar
    • Export Citation
  • 18.

    Houtteville JP. Brain cavernoma: a dynamic lesion. Surg Neurol 48:610614, 1997 Houtteville JP. Brain cavernoma: a dynamic lesion. Surg Neurol 48:610–614, 1997

    • Search Google Scholar
    • Export Citation
  • 19.

    Jain KK, & Robertson E: Recurrence of an excised cavernous hemangioma in the opposite cerebral hemisphere. Case report. J Neurosurg 33:453456, 1970 Jain KK, Robertson E: Recurrence of an excised cavernous hemangioma in the opposite cerebral hemisphere. Case report. J Neurosurg 33:453–456, 1970

    • Search Google Scholar
    • Export Citation
  • 20.

    Kiliç T, , Pamir MN, , Küllü S, , Eren F, , Ozek MM, & Black PMcL: Expression of structural proteins and angiogenic factors in cerebrovascular anomalies. Neurosurgery 46:11791192, 2000 Kiliç T, Pamir MN, Küllü S, Eren F, Ozek MM, Black PMcL: Expression of structural proteins and angiogenic factors in cerebrovascular anomalies. Neurosurgery 46:1179–1192, 2000

    • Search Google Scholar
    • Export Citation
  • 21.

    Kondziolka D, , Lunsford LD, & Kestle JRW: The natural history of cerebral cavernous malformations. J Neurosurg 83:820824, 1995 Kondziolka D, Lunsford LD, Kestle JRW: The natural history of cerebral cavernous malformations. J Neurosurg 83:820–824, 1995

    • Search Google Scholar
    • Export Citation
  • 22.

    Labauge P, , Brunereau L, , Coubes P, , Clanet M, , Tannier C, & Laberge S, et al: Appearance of new lesions in two nonfamilial cerebral cavernoma patients. Eur Neurol 45:8388, 2001 Labauge P, Brunereau L, Coubes P, Clanet M, Tannier C, Laberge S, et al: Appearance of new lesions in two nonfamilial cerebral cavernoma patients. Eur Neurol 45:83–88, 2001

    • Search Google Scholar
    • Export Citation
  • 23.

    Larson JJ, , Ball WS, , Bove KE, , Crone KR, & Tew JM Jr: Formation of intracerebral cavernous malformations after radiation treatment for central nervous system neoplasia in children. J Neurosurg 88:5156, 1998 Larson JJ, Ball WS, Bove KE, Crone KR, Tew JM Jr: Formation of intracerebral cavernous malformations after radiation treatment for central nervous system neoplasia in children. J Neurosurg 88:51–56, 1998

    • Search Google Scholar
    • Export Citation
  • 24.

    Laurans MS, , DiLuna ML, , Shin D, , Niazi F, , Voorhees JR, & Nelson-Williams C, et al: Mutational analysis of 206 families with cavernous malformations. J Neurosurg 99:3843, 2003 Laurans MS, DiLuna ML, Shin D, Niazi F, Voorhees JR, Nelson-Williams C, et al: Mutational analysis of 206 families with cavernous malformations. J Neurosurg 99:38–43, 2003

    • Search Google Scholar
    • Export Citation
  • 25.

    Liquori CL, , Berg MJ, , Siegel AM, , Huang E, , Zawistowski JS, & Stoffer T, et al: Mutations in a gene encoding a novel phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. Am J Hum Genet 73:14591464, 2003 Liquori CL, Berg MJ, Siegel AM, Huang E, Zawistowski JS, Stoffer T, et al: Mutations in a gene encoding a novel phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. Am J Hum Genet 73:1459–1464, 2003

    • Search Google Scholar
    • Export Citation
  • 26.

    Massa-Micon B, , Luparello V, , Bergui M, & Pagni CA: De novo cavernoma case report and review of literature. Surg Neurol 53:484487, 2000 Massa-Micon B, Luparello V, Bergui M, Pagni CA: De novo cavernoma case report and review of literature. Surg Neurol 53:484–487, 2000

    • Search Google Scholar
    • Export Citation
  • 27.

    Matsubara S, , Bourdeau A, , terBrugge KG, , Wallace C, & Letarte M: Analysis of endoglin expression in normal brain tissue and in cerebral arteriovenous malformations. Stroke 31:26532660, 2000 Matsubara S, Bourdeau A, terBrugge KG, Wallace C, Letarte M: Analysis of endoglin expression in normal brain tissue and in cerebral arteriovenous malformations. Stroke 31:2653–2660, 2000

    • Search Google Scholar
    • Export Citation
  • 28.

    McCormick WF: The pathology of vascular (“arteriovenous”) malformations. J Neurosurg 24:807816, 1966 McCormick WF: The pathology of vascular (“arteriovenous”) malformations. J Neurosurg 24:807–816, 1966

    • Search Google Scholar
    • Export Citation
  • 29.

    Miyazawa T, , Sure U, & Bertalanffy H: [Surgical treatment of brainstem cavernous malformation.] No Shinkei Geka 31:851866, 2003 (Jpn) Miyazawa T, Sure U, Bertalanffy H: [Surgical treatment of brainstem cavernous malformation.] No Shinkei Geka 31:851–866, 2003 (Jpn)

    • Search Google Scholar
    • Export Citation
  • 30.

    Moriarity JL, , Wetzel M, , Clatterbuck RE, , Javedan S, , Sheppard JM, & Hoenig-Rigamonti K, et al: The natural history of cavernous malformations: a prospective study of 68 patients. Neurosurgery 44:11661173, 1999 Moriarity JL, Wetzel M, Clatterbuck RE, Javedan S, Sheppard JM, Hoenig-Rigamonti K, et al: The natural history of cavernous malformations: a prospective study of 68 patients. Neurosurgery 44:1166–1173, 1999

    • Search Google Scholar
    • Export Citation
  • 31.

    Notelet L, , Houtteville JP, , Khoury S, , Lechevalier B, & Chapon F: Proliferating cell nuclear antigen (PCNA) in cerebral cavernomas:an immunhistochemical study of 42 cases. Surg Neurol 47:364370, 1997 Notelet L, Houtteville JP, Khoury S, Lechevalier B, Chapon F: Proliferating cell nuclear antigen (PCNA) in cerebral cavernomas:an immunhistochemical study of 42 cases. Surg Neurol 47:364–370, 1997

    • Search Google Scholar
    • Export Citation
  • 32.

    Plate KH, , Breier G, , Millauer B, , Ullrich A, & Risau W: Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res 53:58225827, 1993 Plate KH, Breier G, Millauer B, Ullrich A, Risau W: Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res 53:5822–5827, 1993

    • Search Google Scholar
    • Export Citation
  • 33.

    Porter PJ, , Willinsky RA, , Harper W, & Wallace MC: Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage. J Neurosurg 87:190197, 1997 Porter PJ, Willinsky RA, Harper W, Wallace MC: Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage. J Neurosurg 87:190–197, 1997

    • Search Google Scholar
    • Export Citation
  • 34.

    Pozzati E, , Acciarri N, , Tognetti F, , Marliani F, & Giangaspero F: Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas. Neurosurgery 38:662670, 1996 Pozzati E, Acciarri N, Tognetti F, Marliani F, Giangaspero F: Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas. Neurosurgery 38:662–670, 1996

    • Search Google Scholar
    • Export Citation
  • 35.

    Pozzati E, , Giangaspero F, , Marliani F, & Acciarri N: Occult cerebrovascular malformations after irradiation. Neurosurgery 39:677684, 1996 Pozzati E, Giangaspero F, Marliani F, Acciarri N: Occult cerebrovascular malformations after irradiation. Neurosurgery 39:677–684, 1996

    • Search Google Scholar
    • Export Citation
  • 36.

    Pozzati E, , Giuliani G, , Nuzzo G, & Poppi M: The growth of cerebral cavernous angiomas. Neurosurgery 25:9297, 1989 Pozzati E, Giuliani G, Nuzzo G, Poppi M: The growth of cerebral cavernous angiomas. Neurosurgery 25:92–97, 1989

    • Search Google Scholar
    • Export Citation
  • 37.

    Rigamonti D, , Drayer BP, , Johnson PC, , Hadley MN, , Zabramski J, & Spetzler RF: The MRI appearance of cavernous malformations (angiomas). J Neurosurg 67:518524, 1987 Rigamonti D, Drayer BP, Johnson PC, Hadley MN, Zabramski J, Spetzler RF: The MRI appearance of cavernous malformations (angiomas). J Neurosurg 67:518–524, 1987

    • Search Google Scholar
    • Export Citation
  • 38.

    Rigamonti D, , Hadley MN, , Drayer BP, , Johnson PC, , Hoenig-Rigamonti K, & Knight JT, et al: Cerebral cavernous malformations. Incidence and familial occurence. N Engl J Med 319:343347, 1988 Rigamonti D, Hadley MN, Drayer BP, Johnson PC, Hoenig-Rigamonti K, Knight JT, et al: Cerebral cavernous malformations. Incidence and familial occurence. N Engl J Med 319:343–347, 1988

    • Search Google Scholar
    • Export Citation
  • 39.

    Rigamonti D, , Johnson PC, , Spetzler RF, , Hadley MN, & Drayer BP: Cavernous malformations and capillary teleangiectasia: a spectrum within a single pathological entity. Neurosurgery 28:6064, 1991 Rigamonti D, Johnson PC, Spetzler RF, Hadley MN, Drayer BP: Cavernous malformations and capillary teleangiectasia: a spectrum within a single pathological entity. Neurosurgery 28:60–64, 1991

    • Search Google Scholar
    • Export Citation
  • 40.

    Robinson JR, , Awad IA, & Little JR: Natural history of the cavernous angioma. J Neurosurg 75:709714, 1991 Robinson JR, Awad IA, Little JR: Natural history of the cavernous angioma. J Neurosurg 75:709–714, 1991

    • Search Google Scholar
    • Export Citation
  • 41.

    Robinson JR Jr, , Awad IA, , Magdinec M, & Paranandi L: Factors predisposing to clinical disability in patients with cavernous malformations of the brain. Neurosurgery 32:730736, 1993 Robinson JR Jr, Awad IA, Magdinec M, Paranandi L: Factors predisposing to clinical disability in patients with cavernous malformations of the brain. Neurosurgery 32:730–736, 1993

    • Search Google Scholar
    • Export Citation
  • 42.

    Rosahl SK, , Vorkapic P, , Eghbal R, , Ostertag H, & Samii M: Ossified and de novo cavernous malformations in the same patient. Clin Neurol Neurosurg 100:138143, 1998 Rosahl SK, Vorkapic P, Eghbal R, Ostertag H, Samii M: Ossified and de novo cavernous malformations in the same patient. Clin Neurol Neurosurg 100:138–143, 1998

    • Search Google Scholar
    • Export Citation
  • 43.

    Rothbart D, , Awad IA, , Lee J, , Kim J, , Harbaugh R, & Criscuolo GR: Expression of angiogenic factors and structural proteins in central nervous system vascular malformations. Neurosurgery 38:915925, 1996 Rothbart D, Awad IA, Lee J, Kim J, Harbaugh R, Criscuolo GR: Expression of angiogenic factors and structural proteins in central nervous system vascular malformations. Neurosurgery 38:915–925, 1996

    • Search Google Scholar
    • Export Citation
  • 44.

    Sahoo T, , Johnson EW, , Thomas JW, , Kuehl PM, , Jones TL, & Dokken CG, et al: Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1). Hum Mol Genet 8:23252333, 1999 Sahoo T, Johnson EW, Thomas JW, Kuehl PM, Jones TL, Dokken CG, et al: Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1). Hum Mol Genet 8:2325–2333, 1999

    • Search Google Scholar
    • Export Citation
  • 45.

    Siegel AM, , Andermann E, , Badhwar A, , Rouleau GA, , Wolford GL, & Andermann F, et al: Anticipation in familial cavernous angioma:a study of 52 families from International Familial Cavernous Angioma Study. IFCAS Group. Lancet 352:16761677, 1998 Siegel AM, Andermann E, Badhwar A, Rouleau GA, Wolford GL, Andermann F, et al: Anticipation in familial cavernous angioma:a study of 52 families from International Familial Cavernous Angioma Study. IFCAS Group. Lancet 352:1676–1677, 1998

    • Search Google Scholar
    • Export Citation
  • 46.

    Sonstein WJ, , Kader A, , Michelsen WJ, , Llena JF, , Hirano A, & Casper D: Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study. J Neurosurg 85:838845, 1996 Sonstein WJ, Kader A, Michelsen WJ, Llena JF, Hirano A, Casper D: Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study. J Neurosurg 85:838–845, 1996

    • Search Google Scholar
    • Export Citation
  • 47.

    Stacey RJ, , Ashkan K, & Edwards JM: Rapid growth in a cavernoma. Br J Neurosurg 14:585588, 2000 Stacey RJ, Ashkan K, Edwards JM: Rapid growth in a cavernoma. Br J Neurosurg 14:585–588, 2000

    • Search Google Scholar
    • Export Citation
  • 48.

    Steiger HJ, , Markwalder TM, & Reulen HJ: Clinicopathological relations of cerebral cavernous angiomas: observations in eleven cases. Neurosurgery 21:879884, 1987 Steiger HJ, Markwalder TM, Reulen HJ: Clinicopathological relations of cerebral cavernous angiomas: observations in eleven cases. Neurosurgery 21:879–884, 1987

    • Search Google Scholar
    • Export Citation
  • 49.

    Sure U, , Battenberg E, , Dempfle A, , Tirakotai W, , Bien S, & Bertalanffy H: Hypoxia-inducible factor and vascular endothelial growth factor is expressed more frequently in embolized than in nonembolized cerebral arteriovenous malformations. Neurosurgery 55:663670, 2004 Sure U, Battenberg E, Dempfle A, Tirakotai W, Bien S, Bertalanffy H: Hypoxia-inducible factor and vascular endothelial growth factor is expressed more frequently in embolized than in nonembolized cerebral arteriovenous malformations. Neurosurgery 55:663–670, 2004

    • Search Google Scholar
    • Export Citation
  • 50.

    Sure U, , Benes L, , Riegel T, , Schulte DM, & Bertalanffy H: Image fusion for skull base neuronavigation. Technical note. Neurol Med Chir 42:458462, 2002 Sure U, Benes L, Riegel T, Schulte DM, Bertalanffy H: Image fusion for skull base neuronavigation. Technical note. Neurol Med Chir 42:458–462, 2002

    • Search Google Scholar
    • Export Citation
  • 51.

    Sure U, , Butz N, , Schlegel J, , Siegel AM, , Wakat JP, & Mennel HD, et al: Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations. J Neurosurg 94:972977, 2001 Sure U, Butz N, Schlegel J, Siegel AM, Wakat JP, Mennel HD, et al: Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations. J Neurosurg 94:972–977, 2001

    • Search Google Scholar
    • Export Citation
  • 52.

    Sure U, , Butz N, , Siegel AM, , Mennel HD, , Bien S, & Bertalanffy H: Treatment-induced neoangiogenesis in cerebral arteriovenous malformations. Clin Neurol Neurosurg 103:2932, 2001 Sure U, Butz N, Siegel AM, Mennel HD, Bien S, Bertalanffy H: Treatment-induced neoangiogenesis in cerebral arteriovenous malformations. Clin Neurol Neurosurg 103:29–32, 2001

    • Search Google Scholar
    • Export Citation
  • 53.

    Tirakotai W, , Sure U, , Benes L, , Krischek B, , Bien S, & Bertalanffy H: Image-guided transsylvian, transinsular approach for insular cavernous angiomas. Neurosurgery 53:12991305, 2003 Tirakotai W, Sure U, Benes L, Krischek B, Bien S, Bertalanffy H: Image-guided transsylvian, transinsular approach for insular cavernous angiomas. Neurosurgery 53:1299–1305, 2003

    • Search Google Scholar
    • Export Citation
  • 54.

    Uranishi R, , Baev NI, , Ng PY, , Kim JH, & Awad IA: Expression of endothelial cell angiogenesis receptors in human cerebrovascular malformations. Neurosurgery 48:359368, 2001 Uranishi R, Baev NI, Ng PY, Kim JH, Awad IA: Expression of endothelial cell angiogenesis receptors in human cerebrovascular malformations. Neurosurgery 48:359–368, 2001

    • Search Google Scholar
    • Export Citation
  • 55.

    Verlaan DJ, , Davenport WJ, , Stefan H, , Sure U, , Siegel AM, & Rouleau GA: Cerebral cavernous malformations: mutations in the Krit1. Neurology 58:853857, 2002 Verlaan DJ, Davenport WJ, Stefan H, Sure U, Siegel AM, Rouleau GA: Cerebral cavernous malformations: mutations in the Krit1. Neurology 58:853–857, 2002

    • Search Google Scholar
    • Export Citation
  • 56.

    Verlaan DJ, , Laurent SB, , Sure U, , Bertalanffy H, , Andermann E, & Andermann F, et al: CCM1 mutation screen of individuals sporadical cases with cerebral cavernous malformations. Neurology 62:12131215, 2004 Verlaan DJ, Laurent SB, Sure U, Bertalanffy H, Andermann E, Andermann F, et al: CCM1 mutation screen of individuals sporadical cases with cerebral cavernous malformations. Neurology 62:1213–1215, 2004

    • Search Google Scholar
    • Export Citation
  • 57.

    Verlaan DJ, , Siegel AM, & Rouleau GA: Krit1 missense mutations lead to splicing errors in cerebral cavernous malformations. Am J Hum Genet 70:15641567, 2002 Verlaan DJ, Siegel AM, Rouleau GA: Krit1 missense mutations lead to splicing errors in cerebral cavernous malformations. Am J Hum Genet 70:1564–1567, 2002

    • Search Google Scholar
    • Export Citation
  • 58.

    Zagzag D, , Zhong H, , Scalzitti JM, , Laughner E, , Simons JW, & Semenza GL: Expression of hypoxia-inducible factor 1α in brain tumors: association with angiogenesis, invasion, and progression. Cancer 88:26062618, 2000 Zagzag D, Zhong H, Scalzitti JM, Laughner E, Simons JW, Semenza GL: Expression of hypoxia-inducible factor 1α in brain tumors: association with angiogenesis, invasion, and progression. Cancer 88:2606–2618, 2000

    • Search Google Scholar
    • Export Citation
  • 59.

    Zambramski JM, , Wascher TM, , Spetzler RF, , Johnson B, , Golfinos J, & Drayer BP, et al: The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg 80:422432, 1994 Zambramski JM, Wascher TM, Spetzler RF, Johnson B, Golfinos J, Drayer BP, et al: The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg 80:422–432, 1994

    • Search Google Scholar
    • Export Citation
  • 60.

    Zimmerman RS, , Spetzler RF, , Lee KS, , Zabramski JM, & Hargraves RW: Cavernous malformations of the brain stem. J Neurosurg 75:3239, 1991 Zimmerman RS, Spetzler RF, Lee KS, Zabramski JM, Hargraves RW: Cavernous malformations of the brain stem. J Neurosurg 75:32–39, 1991

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