Background: The natural history of cavernous malformations (CMs) has remained unclear. This lack of knowledge has made treatment decisions difficult. Indeed, the use of stereotactic radiosurgery is nowadays controversial. The purpose of this paper is to throw light on the effectiveness of Gamma Knife radiosurgery (GKRS) therapy. Methods: The authors reviewed data collected from a prospectively maintained database. A total of 95 patients (57 female and 38 male) underwent GKRS for high-surgical-risk CMs. A total of 76 cavernomas were deeply located (64 lesions in the brainstem and 12 lesions in the thalamus). All of them were located in eloquent regions. The median malformation volume was 1,570 mm3. The median tumor margin dose was 11.87 Gy, and the mean tumor maximum dose was 19.56 Gy. Results: Ninety-five cavernous CMs were managed from 1994 to 2014. All patients had experienced at least 1 symptomatic bleeding incident before treatment (only 1 hemorrhage event in 81%). The median length of follow-up review was 78 months. The pretreatment annual hemorrhage rate was 3.06% compared with 1.4% during the first 3-year latency interval, and 0.16% thereafter (p = 0.004). Four patients developed new location-dependent neurological deficits, and 3 patients had edema-related headache after radiosurgery. All of them presented full recovery. Conclusions: The best dosage range for preventing bleeding was identified as between 11 and 12 Gy in our series. Although the efficacy of radiosurgery in CMs remains impossible to quantify, a very significant reduction in the bleeding rate occurs after a 3-year latency interval. No permanent neurological morbidity is reported in our series. These results defend the safety of GKRS in surgical high-risk CM from the first bleeding event.

1.
Lanzino G, Spetzler RF (eds): Cavernous Malformations of the Brain and Spinal Cord. New York, Thieme, 2008, p 139.
2.
Nagy G, Razak A, Rowe JG, Hodgson TJ, Coley SC, Radatz MW, et al: Stereotactic radiosurgery for deep-seated cavernous malformations: a move toward more active, early intervention. Clinical article. J Neurosurg 2010;113:691-699.
3.
Porter RW, Detwiler PW, Spetzler RF, Lawton MT, Baskin JJ, Derksen PT, et al: Cavernous malformations of the brainstem: experience with 100 patients. J Neurosurg 1999;90:50-58.
4.
Robinson JR, Awad IA, Little JR: Natural history of the cavernous angioma. J Neurosurg 1991;75:709-714.
5.
Lunsford LD, Khan AA, Niranjan A, Kano H, Flickinger JC, Kondziolka D: Stereotactic radiosurgery for symptomatic solitary cerebral cavernous malformations considered high risk for resection. J Neurosurg 2010;113:23-29.
6.
Abdulrauf SI, Kaynar MY, Awad IA: A comparison of the clinical profile of cavernous malformations with and without associated venous malformations. Neurosurgery 1999;44:41-46; discussion 46-47.
7.
Kamezawa T, Hamada J, Niiro M, Kai Y, Ishimaru K, Kuratsu J: Clinical implications of associated venous drainage in patients with cavernous malformation. J Neurosurg 2005;102:24-28.
8.
Rigamonti D: Cavernous Malformations of the Nervous System. Cambridge, Cambridge University Press, 2011.
9.
Kondziolka D, Lunsford LD, Flickinger JC, Kestle JR: Reduction of hemorrhage risk after stereotactic radiosurgery for cavernous malformations. J Neurosurg 1995;83:825-831.
10.
Lee C-C, Pan DH-C, Chung W-Y, Liu K-D, Yang H-C, Wu H-M, et al: Brainstem cavernous malformations: the role of Gamma Knife surgery. J Neurosurg 2012;117(suppl):164-169.
11.
Del Curling O Jr, Kelly DL Jr, Elster AD, Craven TE: An analysis of the natural history of cavernous angiomas. J Neurosurg 1991;75:702-708.
12.
Porter RW, Detwiler PW, Han PP, Spetzler RF: Stereotactic radiosurgery for cavernous malformations: Kjellberg's experience with proton beam therapy in 98 cases at the Harvard Cyclotron. Neurosurgery 1999;44:424-425.
13.
Zabramski 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 1994;80:422-432.
14.
Pollock BE, Garces YI, Stafford SL, Foote RL, Schomberg PJ, Link MJ: Stereotactic radiosurgery for cavernous malformations. J Neurosurg 2000;93:987-991.
15.
Amin-Hanjani S, Ogilvy CS, Candia GJ, Lyons S, Chapman PH: Stereotactic radiosurgery for cavernous malformations: Kjellberg's experience with proton beam therapy in 98 cases at the Harvard Cyclotron. Neurosurgery 1998;42:1229-1236; discussion 1236-1238.
16.
Chang SD, Levy RP, Adler JR Jr, Martin DP, Krakovitz PR, Steinberg GK: Stereotactic radiosurgery of angiographically occult vascular malformations: 14-year experience. Neurosurgery 1998;43:213-220; discussion 220-221.
17.
Karlsson B, Kihlstrom L, Lindquist C, Ericson K, Steiner L: Radiosurgery for cavernous malformations. J Neurosurg 1998;88:293-297.
18.
Liscák R, Vladyka V, Simonova G, Vymazal J, Novotny J Jr: Gamma knife surgery of brain cavernous hemangiomas. J Neurosurg 2005;102(suppl):207-213.
19.
Liu AL, Wang C, Sun S, Wang M, Liu P: Gamma knife radiosurgery for tumors involving the cavernous sinus. Stereotact Funct Neurosurg 2005;83:45-51.
20.
Pozzati E, Acciarri N, Tognetti F, Marliani F, Giangaspero F: Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas. Neurosurgery 1996;38:662-669; discussion 669-670.
21.
Azimi P, Shahzadi S, Bitaraf MA, Azar M, Alikhani M, Zali A, et al: Cavernomas: outcomes after gamma-knife radiosurgery in Iran. Asian J Neurosurg 2015;10:49.
22.
Liscák R: Radiosurgery of brain cavernomas - long-term results. Prog Neurol Surg 2013;27:147-156.
23.
Barker FG 2nd, Amin-Hanjani S, Butler WE, Lyons S, Ojemann RG, Chapman PH, et al: Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system. Neurosurgery 2001;49:15-24; discussion 24-25.
24.
Dammann P, Jabbarli R, Wittek P, Oppong MD, Kneist A, Zhu Y, et al: Solitary sporadic cerebral cavernous malformations: risk factors of first or recurrent symptomatic hemorrhage and associated functional impairment. World Neurosurg 2016;91:73-80.
25.
Gross BA, Du R: Hemorrhage from cerebral cavernous malformations: a systematic pooled analysis. J Neurosurg 2017;126:1079-1087.
26.
Taslimi S, Modabbernia A, Amin-Hanjani S, Barker FG 2nd, Macdonald RL: Natural history of cavernous malformation: systematic review and meta-analysis of 25 studies. Neurology 2016;86:1984-1991.
27.
Liu AL, Wang CC, Dai K: Gamma knife radiosurgery for cavernous malformations (in Chinese). Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2005;27:18-21.
28.
Lee SH, Choi HJ, Shin HS, Choi SK, Oh IH, Lim YJ: Gamma Knife radiosurgery for brainstem cavernous malformations: should a patient wait for the rebleed? Acta Neurochir (Wien) 2014;156:1937-1946.
29.
Kim BS, Yeon JY, Kim JS, Hong SC, Lee JI: Gamma knife radiosurgery of the symptomatic brain stem cavernous angioma with low marginal dose. Clin Neurol Neurosurg 2014;126:110-114.
30.
Kida Y, Hasegawa T, Iwai Y, Shuto T, Satoh M, Kondoh T, et al: Radiosurgery for symptomatic cavernous malformations: a multi-institutional retrospective study in Japan. Surg Neurol Int 2015;6(suppl 5):S249-S257.
31.
Kondziolka D, Lunsford LD, Coffey RJ, Bissonette DJ, Flickinger JC: Stereotactic radiosurgery of angiographically occult vascular malformations: indications and preliminary experience. Neurosurgery 1990;27:892-900.
32.
Kjellberg RN, Hanamura T, Davis KR, Lyons SL, Adams RD: Bragg-peak proton-beam therapy for arteriovenous malformations of the brain. N Engl J Med 1983;309:269-274.
33.
Monaco EA, Khan AA, Niranjan A, Kano H, Grandhi R, Kondziolka D, et al: Stereotactic radiosurgery for the treatment of symptomatic brainstem cavernous malformations. Neurosurg Focus 2010;29:E11.
34.
Lindquist C, Guo WY, Karlsson B, Steiner L: Radiosurgery for venous angiomas. J Neurosurg 1993;78:531-536.
35.
Mathiesen T, Edner G, Kihlstrom L: Deep and brainstem cavernomas: a consecutive 8-year series. J Neurosurg 2003;99:31-37.
36.
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 2002;25:1-53; discussion 54-55.
37.
Hauck EF, Barnett SL, White JA, Samson D: Symptomatic brainstem cavernomas. Neurosurgery 2009;64:61-70; discussion 70-71.
38.
Menon G, Gopalakrishnan CV, Rao BR, Nair S, Sudhir J, Sharma M: A single institution series of cavernomas of the brainstem. J Clin Neurosci 2011;18:1210-1214.
39.
Kim DG, Choe WJ, Paek SH, Chung HT, Kim IH, Han DH: Radiosurgery of intracranial cavernous malformations. Acta Neurochir (Wien) 2002;144:869-878; discussion 878.
40.
Lee SH, Lim YJ: Stereotactic radiosurgery for cavernous malformations: prejudice from ignorance. Acta Neurochir (Wien) 2015;157:51-52.
41.
Sager O, Beyzadeoglu M, Dincoglan F, Uysal B, Gamsiz H, Demiral S, Oysul K, Dirican B, Sirin S: Evaluation of linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) for cerebral cavernous malformations: a 15-year single-center experience. Ann Saudi Med 2014;34:54-58.
42.
Fedorcsak I, Nagy G, Dobai JG, Mezey G, Bognar L: Radiosurgery of intracerebral cavernomas current hungarian practice. Ideggyogy Sz 2015;68:243-251.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.