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Pediatric Cavernous Malformations

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Pediatric Vascular Neurosurgery

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Abstract

Pediatric cavernous malformations (CMs) are rare lesions that arise congenitally or de novo secondary to radiation therapy. Most CMs occur spontaneously, with a small portion inherited genetically. Symptomatology relates to location with supratentorial CMs more often presenting with seizures, and infratentorial presenting with neurologic deficits from a small annual hemorrhage risk. CT and MRI have high sensitivities in lesion detection, while angiography is typically negative. Management decisions should largely be based on symptoms, location, hemorrhage risk and seizure control. While a majority of seizures are controlled with medications, up to 30% remain drug-resistant. Surgical resection significantly reduces seizure burden, with about 3/4 achieving Engel Class I overall. A larger proportion experience seizure freedom with resection of the perilesional hemosiderin rim in addition to the lesion itself. Brainstem CMs incur a high complication risk; nevertheless certain attributes, such as large, exophytic lesions or those <2 mm from the pial surface, should prompt consideration for resection. Radiosurgery provides questionable benefit with significant complication and thus should be avoided. Alternative modalities such as magnetic-resonance guided focused ultrasound or laser interstitial thermal therapy hold potential as viable treatment options, although further investigation is required.

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References

  1. Lee JW, Kim DS, Shim KW, Chang JH, Huh SK, Park YG, Choi JU. Management of intracranial cavernous malformation in pediatric patients. Childs Nerv Syst. 2008;24(3):321–7.

    Article  PubMed  Google Scholar 

  2. Mottolese C, Hermier M, Stan H, Jouvet A, Saint-Pierre G, Froment J-C, Bret P, Lapras C. Central nervous system cavernomas in the pediatric age group. Neurosurg Rev. 2001;24:55–71.

    Article  CAS  PubMed  Google Scholar 

  3. Giombini S, Morello G. Cavernous angiomas of the brain. Account of fourteen personal cases and review of the literature. Acta Neurochir (Wien). 1978;40(1–2):61–82.

    Google Scholar 

  4. Lonjon M, Roche J, George B, Mourier K, Paquis P, Lot G, et al. Intracranial cavernoma. 30 cases. Presse Med. 1993;22(21):990–994.

    Google Scholar 

  5. McCormick W, Hardman J, Boulter T. Vascular malformations (angiomas) of the brain with special reference to those occuring in the posterior fossa. J Neurosurg. 1968;28:241–51.

    Article  CAS  PubMed  Google Scholar 

  6. Rigamonti D, Hadley M, Drayer B, Johnson P, Hoenig-Rigamonti K, Knight J, et al. Cerebral cavernous malformations. Incidence and familial occurrence. N Engl J Med. 1988;319(6):343–347.

    Google Scholar 

  7. Li D, Hao S, Tang J, Xiao X, Jia G, Wu Z, Zhang L, Zhang J. Surgical management of pediatric brainstem cavernous malformations. J Neurosurg Pediatr. 2014;13:484–502.

    Article  PubMed  Google Scholar 

  8. Acciarri N, Galassi E, Giulioni M, Pozzati E, Grasso V, Palandri G, Badaloni F, Zucchelli M, Calbucci F. Cavernous malformations of the central nervous system in the pediatric age group. Pediatr Neurosurg. 2009;45(2):81–104.

    Article  PubMed  Google Scholar 

  9. Gross BA, Du R, Orbach DB, Scott RM, Smith ER. The natural history of cerebral cavernous malformations in children. J Neurosurg Pediatr. 2015;1–6.

    Google Scholar 

  10. Van Gompel JJ, Rubio J, Cascino GD, Worrell GA, Meyer FB. Electrocorticography-guided resection of temporal cavernoma: Is electrocorticography warranted and does it alter the surgical approach? J Neurosurg. 2009;110:1179–85.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ghali MG, Srinivasan VM, Mohan AC, Jones JY, Kan PT, Lam S. Pediatric cerebral cavernous malformations: genetics, pathogenesis, and management. Surg Neurol Int. 2016;7(44):S1127–S1134.

    Google Scholar 

  12. Englot DJ, Han SJ, Lawton MT, Chang EF. Predictors of seizure freedom in the surgical treatment of supratentorial cavernous malformations. J Neurosurg. 2011;115:1169–74.

    Article  PubMed  Google Scholar 

  13. Xia C, Zhang R, Mao Y, Zhou L. Pediatric cavernous malformation in the central nervous system: report of 66 cases. Pediatr Neurosurg. 2009;45(2):105–13.

    Article  PubMed  Google Scholar 

  14. Knerlich-Lukoschus F, Steinbok P, Dunh C, Cochrane DD. Cerebellar cavernous malformation in pediatric patients: defining clinical, neuroimaging, and therapeutic characteristics. J Neurosurg. 2015;16(3):256–66.

    Google Scholar 

  15. Berry R, Alpers B, White J. The site, structure and frequency of intracranial aneurysms, angiomas and arteriovenous abnormalities. In: C M, editor. Research Publications: Association for Research in Nervous and Mental Disease. Baltimore: Williams and Wilkins; 1966. pp. 4–72.

    Google Scholar 

  16. Otten P, Pizzolato G, Rilliet B, Berney J. 131 cases of cavernous angioma (cavernomas) of the CNS, discovered by retrospective analysis of 24,535 autopsies. Neurochirurgie. 1989;35(2):128–31.

    Google Scholar 

  17. DelCurling OJ. DL DJK, Elster A, Craven T: An analysis of the natural history of cavernous angiomas. J Neurosurg. 1991;75(5):702–8.

    Article  Google Scholar 

  18. Sage M, Brophy B, Sweeney C, Phipps S, Perrerr L, Sandhu A, et al. Cavernous haemangiomas (angiomas) of the brain: Clinically significant lesions. Australas Radiol. 1993;37:147–55.

    Article  CAS  PubMed  Google Scholar 

  19. Von der Brelie C, Kuczaty S, von Lehe M. Surgical management and long-term outcome of pediatric patients with different subtypes of epilepsy associated with cerebral cavernous malformations. J Neurosurg Pediatr. 2014;13(6):699–705.

    Google Scholar 

  20. Al-Holou WN, O'Lynnger TM, Pandey AS, Gemmete JJ, Thompson BG, Muraszko KM. Natural history and imaging prevalence of cavernous malformations in children and young adults. J Neurosurg Pediatr. 2012;9:198–205.

    Google Scholar 

  21. Stavrou I, Baumgartner C, Frischer JM, Trattnig S, Knosp E. Long-term seizure control after resection of supratentorial cavernomas: A retrospective single-center study in 53 patients. Neurosurgery. 2008;63:888–96.

    Article  PubMed  Google Scholar 

  22. Edwards M, Baumgartner J, Wilson C. Cavernous and other cryptic vascular malfromations in the pediatric age group. In: Awad I, Barrow D, editors. Cavernous Malformations. Park Ridge: AANS; 1993. pp. 163–183.

    Google Scholar 

  23. Maraire J, Awad I. Intracranial cavernous malformations: lesion behavior and management strategies. Neurosurgery. 1995;37(4):591–605.

    Article  CAS  PubMed  Google Scholar 

  24. Tekkok I, Ventureyra E. De novo familial cavernous malformation presenting with hemorrhage 12.5 years after the initial hemorrhagic ictus: natural hisotory of an infantile form. Pediatr Neurosurg. 1996;25(3):151–155.

    Google Scholar 

  25. Gastelum E, Sear K, Hills N, Roddy E, Randazzo D, Chettout N, Hess C, Cotter J, Haas-Kogan DA, Fullerton H, Mueller S. Rates and characteristics of radiographically detected intracerebral cavernous malformations after cranial radiation therapy in pediatric cancer patients. J Child Neurol. 2015;30(7):842–849.

    Google Scholar 

  26. Detwiler P, Porter R, Zabramski J, Spetzler R. 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. 1997;87(4):629–632.

    Google Scholar 

  27. Larson J, Ball W, Bove K, Crone K, Tew JJ. Formation of intracerebral cavernous malformations after radiation treatment for central nervous system neoplasia in children. J Neurosurg. 1998;88(1):51–6.

    Article  CAS  PubMed  Google Scholar 

  28. Wilson C. Cryptic vascular malformations. Clin Neurosurg. 1992;38:49–84.

    CAS  PubMed  Google Scholar 

  29. Mindea S, Yang B, Shenkar R, Bendok B, Batjer H, Awad I. Cerebral cavernous malformations: clinical insights from genetic studies. Neurosurg Focus. 2006;21:e1.

    PubMed  Google Scholar 

  30. Gunel M, Awad IA, Anson J, Lifton RP. Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21. Proc Natl Acad Sci USA. 1995;92(14):6620–4.

    Google Scholar 

  31. Dashti S, Hoffer A, Hu Y, Selman W. Molecular genetics of familial cerebral cavernous malformations. Neurosurg Focus. 2006;21:e2.

    Article  PubMed  Google Scholar 

  32. Dubovsky J, Zabramski J, Kurth J, Spetzler R, Rich S, Orr H, et al. A gene responsible for cavernous malformations of the brain maps to chromosome 7q. Hum Mol Genet. 1995;4(3):453–8.

    Article  CAS  PubMed  Google Scholar 

  33. Gunel M, Awad I, Finberg K, Anson J, Batjer GSH, Kopitnik T, et al. A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans. N Engl J Med. 1996;334(15):946–951.

    Google Scholar 

  34. Revencu N, Vikkula M. Cerebral cavernous malformation: new molecular and clinical insights. J Med Genet. 2006;43:716–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zabramski JM, Wascher TM, Spetzler RF, Johnson B, Golfinos J, Drayer B, Brown B, Rigamonti D, Brown G. The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg. 1994;80:422–32.

    Article  CAS  PubMed  Google Scholar 

  36. Aiba T, Tanaka R, Koike T, Kameyama S, Takeda N, Komata T. Natural history of intracranial cavernous malformations. J Neurosurg. 1995;83(1):56–9.

    Article  CAS  PubMed  Google Scholar 

  37. Al-Shahi Salman R, Hall JM, Horne MA, Moultrie F, Josephson CB, Bhattacharya JJ, et al. Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study. Lancet Neurol. 2012;11:217–224.

    Google Scholar 

  38. Flemming K, Link M, Christianson T. RD Brown J: The Prospective Hemorrhage risk of intracerebral cavernous malformations. Neurology. 2012;78:632–6.

    Article  CAS  PubMed  Google Scholar 

  39. Kim D, Park Y, Choi J, Chung S, Lee K. An analysis of the natural history of cavernous malformations. Surg Neurol. 1997;48(1):9–18.

    Article  CAS  PubMed  Google Scholar 

  40. Kondziolka D, Lunsford L, Kestle J. The natural history of cerebral cavernous malformations. J Neurosurg. 1995;83(5):820–4.

    Article  CAS  PubMed  Google Scholar 

  41. Kupersmith M, Kalish H, Epstein F, Yu G, Berenstein A, Woo H, et al. Natural history of brainstem cavernous malformations. Neurosurgery. 2001;48:47–54.

    CAS  PubMed  Google Scholar 

  42. Moriarity J, Clatterbuck R, Rigamonti D. The natural history of cavernous malformations. Neurosurg Clin N Am. 1999;10(3):411–7.

    Article  CAS  PubMed  Google Scholar 

  43. Pasqualin A, Vivenza C, Rosta L, Scienza R, Pien RD, Colangeli M. Spontaneous regression of intracranial arteriovenous malformation. Surg Neurol. 1993;39:385–91.

    Article  Google Scholar 

  44. Porter P, Willinsky R, Harper W, Wallace M. Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage. J Neurosurg. 1997;87(2):190–7.

    Article  CAS  PubMed  Google Scholar 

  45. Robinson J, Awad I, Little J. Natural history of the cavernous angioma. J Neurosurg. 1991;75(5):709–14.

    Article  CAS  PubMed  Google Scholar 

  46. Voigt K, Yasargil M. Cerebral cavernous haemangiomas or cavernomas. Incidence, pathology, localization, diagnosis, clinical features and treatment. Review of the literature and report of an unusual case. Neurochirurgia (Stuttg). 1976;19(2):59–68.

    Google Scholar 

  47. Abdulrauf S, Kaynar M, Awad I. A comparison of the clinical profile of cavernous malformations with and without associated venous malformations. Neurosurgery. 1999;44(1):41–7.

    Article  CAS  PubMed  Google Scholar 

  48. Cantu C, Murillo-Bonilla L, Arauz A, Higuera J, Padilla J, Barinagarrementeria F. Predictive factors for intracerebral hemorrhage in patients with cavernous angiomas. Neurol Res. 2005;27:314–8.

    Article  PubMed  Google Scholar 

  49. Mathiesen T, Edner G, Kihlstrom L. Deep and brainstem cavernomas: a consecutive 8-year series. J Neurosurg. 2003;99:31–7.

    Article  PubMed  Google Scholar 

  50. Wang W, Liu A, Zhang J, Sun B, Zhao Y. Surgical management of brainstem cavernous malformations: Report of 137 cases. Surg Neurol. 2003;59:444–4542.

    Article  PubMed  Google Scholar 

  51. Barker F, Amin-Hanjani S, Butler W, Lyons S, Ojemann R, Chapman P, et al. Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system. Neurosurgery. 2001;49:15–25.

    Google Scholar 

  52. Rosenow F, Alonso-Vanegas MA, Baumgartner B, Blumcke I, Carreno M, Gizewski ER, et al: Cavernoma-related epilepsy: review and recommendations for mangement—report of the Surgical Task Force of the ILAE Commission on therapeutic strategies. Epilepsia. 2013;54:2025–2035.

    Google Scholar 

  53. Awad I, Jabbour P. Cerebral cavernous malformations and epilepsy. Neurosurg Focus. 2006;21:e7.

    Article  PubMed  Google Scholar 

  54. Song J, Qiao N, Xie L, Qiu T, Li P, Wu J, Zhu W, Chen L, He KM, Zhang N, Mao Y, Zhao Y. Clinical features and microsurgical treatment of pediatric patients with cerebral cavernous malformation. J Clin Neurosci. 2011;18(10):1303–7.

    Article  PubMed  Google Scholar 

  55. Lobato R, Perez C, Rivas J, Cordobes F. Clinical, radiological, and pathological spectrum of angiographically occult intracranialvascular malformations. Analysis of 21 cases and review of the literature. J Neurosurg. 1988;68(4):518–531.

    Google Scholar 

  56. Vaquero J, Leunda G, Martinez R, Bravo G. Cavernomas of the brain. Neurosurgery. 1983;12(2):208–10.

    Article  CAS  PubMed  Google Scholar 

  57. Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B, Kim H, Jusue-Torres I, Kondziolka D, Lee C, Morrison L, Rigamonti D, Rebeiz T, Tournier-Lasserve E, Waggoner D, Whitehead K. Synopsis of guidelines for the clinical management of cerebral cavernous malformations: consensus recommendations based on systematic literature review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel. Neurosurgery 2017;80(5):665–680.

    Google Scholar 

  58. Bien S, Friedburg H, Harders A, Schumacher M. Intracerebral cavernous angiomas in magnetic resonance imaging. Acta Radiol Suppl (Stockh). 1986;369:79–81.

    CAS  Google Scholar 

  59. Lehnhardt F, Smekal Uv, Ruckriem B, Stenzel W, Neveling M, Heiss W, et al. Value of gradient-echo magnetic resonance imaging in the diagnosis of familial cerebral cavernous malformation. Arch Neurol. 2005;62:653–658.

    Google Scholar 

  60. Rapacki T, Brantley M, Furlow TJ, Geyer C, Toro V, George E. Heterogeneity of cerebral cavernous hemangiomas diagnosed by MR imaging. J Comput Assist Tomogr. 1990;14(1):18–25.

    Article  CAS  PubMed  Google Scholar 

  61. Rigamonti D, Drayer B, Johnson P, Hadley M, Zabramski J, Spetzler R. The MRI appearance of cavernous malformations (angiomas). J Neurosurg. 1987;67(4):518–24.

    Article  CAS  PubMed  Google Scholar 

  62. Dammann P, Barth M, Zhu Y, Maderwald S, Schlamann M, Ladd ME, Sure U. Susceptibility weighted magnetic resonance imaging of cerebral cavernous malformations: prospects, drawbacks, and first experience at ultra-high field strength (7-Tesla) magnetic resonance imaging. Neurosurg Focus. 2010;29(3):E5.

    Article  PubMed  Google Scholar 

  63. Servo A, Porras M, Raininko R. Diagnosis of cavernous haemangiomas by computed tomography and angiography. Acta Neurochir (Wien). 1984;71(3–4):273–82.

    Article  CAS  Google Scholar 

  64. Yang PF, Pei JS, Jia YZ, Lin Q, Xiao H, Zhang TT, Zhong ZH. Surgical management and long-term seizure outcome after surgery for temporal lobe epilepsy associated with cerebral cavernous malformations. World Neurosurg. 2018;110:e659–70.

    Article  PubMed  Google Scholar 

  65. Wang CC, Liu A, Zhang JT, Sun B, Zhao YL. Surgical management of brain-stem cavernous malformations: report of 137 cases. Surg Neurol. 2003;59(6):444–54.

    Article  PubMed  Google Scholar 

  66. Kraemer DL, Awad IA. Vascular malformations and epilepsy: Clinical considerations and basic mechanisms. Epilepsia. 1994;35:S30-43.

    Article  PubMed  Google Scholar 

  67. Baumann CR, Schuknecht B, Lo Russo G, Cossu M, Citterio A, Andermann F. Seizure outcome after resection of cavernous malformations is better when surrounding hemosiderin-stained brain also is removed. Epilepsia. 2006;47:563–6.

    Article  PubMed  Google Scholar 

  68. Hammen T, Romstock J, Dorfler A, Kerling F, Buchfelder M, Stefan H. Prediction of postoperative outcome with special respect to removal of hemosiderin fringe: a study in patients with cavernous haemangiomas associated with symptomatic epilepsy. Seizure. 2007;16:248–53.

    Article  CAS  PubMed  Google Scholar 

  69. Kraemer DL, Griebel ML, Lee N, Friedman AH, Radtke RA. Surgical outcome in patients with epilepsy with occult vascular malformations treated with lesionectomy. Epilepsia. 1998;39:600–7.

    Article  CAS  PubMed  Google Scholar 

  70. Stefan H, Hammen T. Cavernous haemangiomas, epilepsy and treatment strategies. Acta Neurol Scand. 2004;110:393–7.

    Article  CAS  PubMed  Google Scholar 

  71. Chang EF, Gabriel RA, Potts MB, Garcia PA, Barbaro NM, Lawton MT. Seizure characteristics and control after microsurgical resection of supratentorial cerebral cavernous malformations. Neurosurgery. 2009;65:31–7.

    Article  PubMed  Google Scholar 

  72. Mouchtouris N, Chalouhi N, Chitale A, Starke RM, Tjoumakaris SI, Rosenwasser RH, Jabbour PM. Management of cerebral cavernous malformations: from diagnosis to treatment. Sci World J . 2015;2015:808314.

    Article  Google Scholar 

  73. Pollock BE, Garces YI, Stafford SL, Foote RL, Schomberg PJ, Link MJ. Stereotactic radiosurgery of cavernous malformations. J Neurosurg. 2011;15(4):987–91.

    Google Scholar 

  74. Gross BA, Smith ER, Goumnerova L, Proctor MR, Madsen JR, Scott RM. Resection of supratentorial lobar cavernous malformations in children: clinical article. J Neurosurg Pediatr. 2013;12(4):367–73.

    Article  PubMed  Google Scholar 

  75. DiRocco C, Iannelli A, Tamburrini G. Cavernous angiomas of the brain stem in children. Pediatr Neurosurg. 1997;27:92–9.

    Article  CAS  Google Scholar 

  76. Paolini S, Morace R, Di Gennaro G, Picardi A, Grammaldo LG, Meldolesi GN, Quarato PP, Raco A, Esposito V. Drug-resistant temporal lobe epilepsy due to cavernous malformations. Neurosurg Focus. 2006;21(1):e8.

    Article  PubMed  Google Scholar 

  77. Abla AA, Lekovic GP, Garrett M, Wilson DA, Nakaji P, Bristol R, Spetzler RF. Cavernous malformations of the brainstem presenting in childhood: surgical experience in 40 patients. Neurosurgery. 2010;67(6):1589–98.

    Article  PubMed  Google Scholar 

  78. Weil S, Tew JM, Steiner L. Comparison of radiosurgery and microsurgery for treatment of cavernous malformations of the brainstem. Abstract J Neurosurg. 1990;72:336A.

    Google Scholar 

  79. Liscak R, Urgosik D, Simonova G, Vymazal J, Semnicka J. Gamma knife radiosurgery of brain cavernomas. Acta Neurochir Suppl. 2013;116:107–11.

    PubMed  Google Scholar 

  80. Nagy G, Kemeny AA. Radiosurgery for cerebral cavernomas. J Neurosurg Sci. 2015;59(3):295–306.

    CAS  PubMed  Google Scholar 

  81. Sheehan J. Transcranial ultrasound for arteriovenous malformations: Something old is new again. World Neurosurg. 2012;77:269–70.

    Article  PubMed  Google Scholar 

  82. Cohen-Inbar O, Xu Z, Sheehan JP. Focused ultrasound-aided immunomodulation in glioblastoma multiforme: a therapeutic concept. J Ther Ultrasound. 2016;4:2.

    Google Scholar 

  83. McCracken DJ, Willie JT, Fernald BA, Saindane AM, Drane DL, Barrow DL. Magnetic resonance thermometry-guided stereotactic laser ablation of cavernous malformations in drug-resistant epilepsy: imaging and clinical results. Neurosurgery. 2015.

    Google Scholar 

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  1. Department of Neurosurgery, Houston Methodist Hospital, 6560 Fannin St., Scurlock Tower, 9th floor, Houston, TX, 77030, USA

    Virendra R. Desai & Gavin W. Britz

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  1. Neuro-Interventional Surgery, Neuro-Interventional Implementation Program, Houston Methodist The Woodlands Hospital, The Woodlands, TX, USA

    Abhishek Agrawal

  2. Department of Neurosurgery, Houston Methodist Neurological Institute, Houston, TX, USA

    Gavin Britz

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Desai, V.R., Britz, G.W. (2021). Pediatric Cavernous Malformations. In: Agrawal, A., Britz, G. (eds) Pediatric Vascular Neurosurgery. Springer, Cham. https://doi.org/10.1007/978-3-030-74749-7_9

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