From AVM to cavernoma: the long-term effects of stereotactic radiosurgery

From AVM to cavernoma: the long-term effects of stereotactic radiosurgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report From AVM to cavernoma: the long-term effects of stereotactic radiosurgery Robin Bouttelgier, Luc Defreyne, Franceska Dedeurwaerdere, Luc Verbeke, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6261419/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Radiation-induced cavernomas are rare but significant late complications of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs). We report the case of a 66-year-old male who developed a contrast-enhancing lesion with cystic necrosis and perilesional edema in the left frontal lobe, 12 years after SRS following transarterial embolization for a partially calcified AVM. Digital subtraction angiography showed no AVM recurrence. Due to progressive anomic aphasia, decreased concentration and reduced initiative, a surgical resection was performed. This confirmed a radiation-induced cavernoma. This case underscores the need for long-term follow-up with multimodal imaging to differentiate late radiation-induced vascular lesions from recurrent pathology. Continuous clinical assessment is crucial for timely intervention, as delayed radiation effects can impact neurological function and patient outcomes. Arteriovenous malformation Cavernoma Endovascular embolization Stereotactic radiosurgery Figures Figure 1 Figure 2 Introduction Arteriovenous malformations (AVMs) are complex cerebrovascular malformations characterized by direct arterial-to-venous connections without an intervening capillary network, leading to abnormal blood flow and an elevated risk of hemorrhage [1]. The major available treatment options include microsurgical resection, endovascular embolization and stereotactic radiosurgery, which can be used independently or in combination depending on the malformation’s characteristics and location. Radiosurgery, while effective in occluding AVMs by promoting vascular damage and thrombosis, can induce delayed adverse effects such as perilesional edema, cyst formation and, in rare cases, radiation-induced neoplasms or vascular proliferative lesions, including cavernomas. This case report presents a post-radiation cavernoma formation at a previously treated AVM site. Case Report A 66-year-old male presented at the neurosurgery department because he slowly developed mild anomic aphasia, decreased concentration and reduced initiative, approximately 12 years after one session of transarterial embolization follow by stereotactic radiosurgery for a partially calcified AVM. The 3.5cm wide AVM nidus was located in the pars orbitalis of the left inferior frontal gyrus. The patient presented initially in 2009 with recurring episodes of overall discomfort and presyncope, without epilepsy nor a bleeding episode. Magnetic resonance imaging (MRI) and digital subtraction angiography (DSA) identified the AVM as Spetzler-Martin grade III with a supplementary grade of 5 [1,2] (Fig. 1 a). After multidisciplinary consultation, surgery was deemed risky because of the high supplemented Spetzler-Martin grade and the language tasks proximity visualized on the pre-treatment functional MRI (fMRI). Therefore, a treatment with endovascular embolization, followed by stereotactic radiosurgery (SRS) was initiated. The size of the nidus could be reduced to 15% via ethylene-vinyl alcohol copolymer (Onyx; Medtronic, Netherlands) injection transarterially (Fig. 1 b-c). Stereotactic radiosurgery followed and after two years, MRI showed a complete occlusion of the AVM with mild perilesional edema. The patient remained stable in the first 5 years of follow-up, after which progressive deterioration of speech and attention occurred. The annual MRI scans and two control DSA’s demonstrated occlusion of the AVM, but gradually increasing post-radiation necrosis and growing cyst formation. The last MRI of the brain demonstrated a contrast-enhancing lesion with a diameter of 2.5 cm as well as fluid-level cysts with perilesional edema in the left frontal lobe (Fig. 2 a). Again, DSA showed no residual nidus. A resection of the radionecrosis and cysts was discussed. The pre-operative fMRI revealed cortical activation of the bilateral inferior frontal gyrus during language tasks. The left inferior frontal gyrus was considered predominant. Therefore, an asleep-awake-asleep craniotomy was performed with complete resection of the contrast-enhancing lesion. Postoperatively, there was a significant reduction of edema (Fig. 2 b). The patient and his relatives noted improved concentration and initiative, with no further word-finding difficulties. Pathological examination of the contrast-enhancing area revealed a cavernoma. Discussion In this case report, we present a rare case of a radiation-induced cavernous malformation at the site of a previously treated AVM. The patient developed clinically significant perilesional edema and cyst formation over 12 years following SRS. Surgical resection was ultimately performed, and histopathological examination revealed a cavernous hemangioma, an uncommon yet noteworthy complication. The therapeutic goal of AVM radiation is obliteration via endothelial damage, smooth muscle cell proliferation and extracellular collagen deposition. These processes eventually lead to intravascular thrombosis and progressive occlusion of the AVM [3]. However, the same mechanisms can trigger long-term adverse changes such as perilesional edema, necrosis, cyst formation and, in rare cases, neoplasia or vascular malformations. Radiation necrosis is influenced by multiple factors. The primary determinant is the radiation dose, with higher doses increasing the likelihood of necrosis. The volume of brain parenchyma exposed to intermediate or high doses (≥ 12 Gy) is particularly significant, although threshold variations exist depending on study methodologies. The total irradiated volume, the number of treated lesions and prior radiation exposure are additional contributing factors. Intrinsic radiosensitivity and lesion location also play important roles, as deeper cerebral lesions tend to be more susceptible compared to superficial ones [4]. In our case, the total irradiated volume and the location of the lesion where the most important factors predisposing to radiation necrosis. Radiation-induced cavernomas are rare but well-documented complications of brain irradiation 2 . Their pathogenesis is multifactorial, potentially involving endothelial injury, disruption of vascular integrity and aberrant angiogenesis triggered by radiation exposure [4]. In the context of AVM radiosurgery, cavernoma formation has been reported several years post-treatment in a few cases. Motegi et al. described a cavernoma 7 years after SRS for an AVM in the right caudate nucleus [5]. Wang et al. reported a similar lesion 6 years post-SRS in the right cerebellum, while Patterson et al. noted a symptomatic cavernoma 7 years after AVM treatment, requiring surgery [6,7]. Notably, similar cases have emerged following irradiation for other intracranial pathologies, such as meningiomas. For instance, Lee et al. described a case with MRI findings resembling our own, where a cavernoma developed after stereotactic irradiation for a meningioma [8]. These similarities underscore a shared pathophysiological pathway regardless of the initial indication for radiation. In Koester et al.'s study of 248 radiation-induced cavernomas, approximately one-third of cases required surgical management [9]. The decision to intervene surgically depends on factors such as lesion size, symptomatic presentation and associated complications like perilesional edema or cyst formation. In our case, surgical resection was indicated due to the presence of clinically significant perilesional edema and persistent cysts, which complicated differential diagnosis and posed a risk for further neurological deterioration. To mitigate the risk of late radiation-induced complications, several preventive strategies can be considered. Recent advancements in embolization techniques, including transvenous approaches, have shown promising results with high curative success rates [10]. More research is needed to reduce the risk of radiation-induced complications. Conclusion This case report describes a rare case of a late radiation-induced histopathological proven cavernoma after AVM treatment. The report underscores long-term monitoring and vigilance post radiotherapy. While generally effective, SRS carries the risk of delayed complications, including cavernoma formation. Advances in radiation delivery techniques are promising in reducing such outcomes. Further research into genetic predispositions and optimized treatment protocols will be crucial in mitigating these rare but impactful complications. Declarations Acknowledgements None Funding Sources and Conflict of Interest No specific funding was received for this study. The authors declare no conflicts of interest relevant to this study. Financial Disclosures No specific funding was received for the study. The authors declare no conflicts of interest relevant to this study. The authors declare that there are no additional disclosures. Ethical Compliance Statement The authors confirm that the approval of an institutional review board for this work was not necessary. Informed consent was obtained from the patient included in the study. We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this work is consistent with these guidelines. Author Contribution R.B. and D.V. were responsible for the conceptualization. R.B., L.D., F.D., L.V. and D.V. collected the data. R.B., L.D. and D.V. wrote the original draft. L.D. prepared the figures, R.B. wrote the figure legends. All authors reviewed the manuscript. References Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg. 1986; 65(4): 476-83. DOI: 10.3171/jns.1986.65.4.0476 Lawton MT, Kim H, McCulloch C. et al. A supplementary grading scale for selecting patients with brain arteriovenous malformations for surgery. Neurosurgery. 2010; 66(4): 702-713. DOI: 10.1227/01.NEU.0000367555.16733.E1 Tsao MN, Li YQ, Lu G. et al. Upregulation of vascular endothelial growth factor is associated with radiation-induced blood-spinal cord barrier breakdown. J Neuropathol Exp Neurol. 1999; 58(10): 1051-60. DOI: 10.1097/00005072-199910000-00003 Vellayappan BA, McGranahan T, Graber J. et al. Radiation necrosis from stereotactic radiosurgery—How do we mitigate? Curr Treat Options Oncol. 2021; 22(7): 57. DOI: 10.1007/s11864-021-00854-z Motegi H, Kuroda S, Ishii N. et al. De novo formation of cavernoma after radiosurgery for adult cerebral arteriovenous malformation. Neurol Med Chir. 2008; 48(9): 397-400. DOI: 10.2176/nmc.48.397 Wang X, Hui X, Liu JP. et al. Radiation-induced cavernous malformation at the site of arteriovenous malformation following gamma knife radiosurgery: Case report. Clin Neurol Neurosurg. 2012; 114(9): 1287-89. DOI: 10.1016/j.clineuro.2012.03.005 Patterson TT, McGinity M, Crownover R. et al. Remote development of symptomatic intracranial cavernous malformation after stereotactic radiosurgery. Cureus. 2022; 14(1): e21635. DOI: 10.7759/cureus.21635 Lee SH, Kim KH, Lee HJ. et al. A huge radiation-induced cavernous hemangioma following stereotactic radiosurgery for meningioma: a case report. Brain Tumor Res Treat. 2022; 10(3): 190-4. DOI: 10.14791/btrt.2022.0020 Koester SW, Rhodenhiser EG, Dabrowski SJ. et al. Radiation-induced cerebral cavernous malformations: a single-center experience and systematic literature review. World Neurosurg. 2023; 179: 222-32. DOI: 10.1016/j.wneu.2023.08.036 Mendes GAC, Kalani MYS, Iosif C. et al. Transvenous curative embolization of cerebral arteriovenous malformations: a prospective cohort study. Neurosurgery. 2018; 83(5): 957-64. DOI: 10.1093/neuros/nyx581 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6261419","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":434412826,"identity":"2dda2fe7-faa8-4d82-ab51-0f09ed4048ee","order_by":0,"name":"Robin Bouttelgier","email":"data:image/png;base64,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","orcid":"","institution":"Ghent University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Robin","middleName":"","lastName":"Bouttelgier","suffix":""},{"id":434412827,"identity":"355d901e-fbe9-4979-8c0a-bb312c62264f","order_by":1,"name":"Luc Defreyne","email":"","orcid":"","institution":"Ghent University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Luc","middleName":"","lastName":"Defreyne","suffix":""},{"id":434412828,"identity":"3c8a534d-747c-4c0a-9215-ea280434d995","order_by":2,"name":"Franceska Dedeurwaerdere","email":"","orcid":"","institution":"AZ Delta","correspondingAuthor":false,"prefix":"","firstName":"Franceska","middleName":"","lastName":"Dedeurwaerdere","suffix":""},{"id":434412829,"identity":"62495b68-a649-4d75-978e-9eb46170f63e","order_by":3,"name":"Luc Verbeke","email":"","orcid":"","institution":"Onze Lieve Vrouwziekenhuis Hospital","correspondingAuthor":false,"prefix":"","firstName":"Luc","middleName":"","lastName":"Verbeke","suffix":""},{"id":434412830,"identity":"8b5bfc61-cc46-4d98-ae18-194baddccaaf","order_by":4,"name":"Wim Maenhoudt","email":"","orcid":"","institution":"AZ Delta","correspondingAuthor":false,"prefix":"","firstName":"Wim","middleName":"","lastName":"Maenhoudt","suffix":""},{"id":434412831,"identity":"7c91b164-5024-4ca8-b605-6a78049f547c","order_by":5,"name":"Stephanie Du Four","email":"","orcid":"","institution":"AZ Delta","correspondingAuthor":false,"prefix":"","firstName":"Stephanie","middleName":"","lastName":"Du Four","suffix":""},{"id":434412832,"identity":"9269e934-74f3-4c68-8eaa-5aed6554c5c8","order_by":6,"name":"Jeroen Van Lerbeirghe","email":"","orcid":"","institution":"AZ Delta","correspondingAuthor":false,"prefix":"","firstName":"Jeroen","middleName":"Van","lastName":"Lerbeirghe","suffix":""},{"id":434412833,"identity":"c17d3744-66f8-47f4-84de-e3b5ab795370","order_by":7,"name":"Olivier Van Damme","email":"","orcid":"","institution":"AZ Delta","correspondingAuthor":false,"prefix":"","firstName":"Olivier","middleName":"Van","lastName":"Damme","suffix":""},{"id":434412834,"identity":"bf61d1f7-d765-48ad-92f5-3de1fd757fc8","order_by":8,"name":"Dimitri Vanhauwaert","email":"","orcid":"","institution":"AZ Delta","correspondingAuthor":false,"prefix":"","firstName":"Dimitri","middleName":"","lastName":"Vanhauwaert","suffix":""}],"badges":[],"createdAt":"2025-03-19 12:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6261419/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6261419/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79657825,"identity":"5fd67379-4ab8-4346-89fd-d65f3e9b6c30","added_by":"auto","created_at":"2025-04-01 09:10:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":188183,"visible":true,"origin":"","legend":"\u003cp\u003eDigital subtraction angiography and AVM embolization\u003c/p\u003e\n\u003cp\u003edemonstrates the digital subtraction angiography (DSA) findings before and after embolization of the AVM. Following catheterization of the left internal carotid artery, the left sagittal view before (Figure 1a) and after embolization (Figure 1b) is visualized. After embolization, the frontolateral nidus is reduced to a small posterior nidus with a single major draining vein. A native skull image (Figure 1c) illustrates the amount of Onyx injected.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6261419/v1/239a155fe217fe149a800cbb.png"},{"id":79657826,"identity":"c26a051c-ef3b-4f19-ab94-7ec3f457189b","added_by":"auto","created_at":"2025-04-01 09:10:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":409984,"visible":true,"origin":"","legend":"\u003cp\u003eT2 MRI before and after neurosurgical resection\u003c/p\u003e\n\u003cp\u003eillustrates the MRI findings before and after surgery. Pre-operative T2-weighted MRI (Figure 2a) shows the mass effect caused by the growing cysts along with increasing edema. Post-surgical imaging (Figure 2b) reveals resolution of the mass effect and complete disappearance of the cysts with a left paramedial frontal defect.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6261419/v1/f807f609b524c32d85fb5b97.png"},{"id":80628061,"identity":"73485118-6d0f-4610-bdee-3f5e40a4fe94","added_by":"auto","created_at":"2025-04-15 11:08:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1121706,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6261419/v1/cc41a130-dda0-4722-bc86-d33a9195741e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"From AVM to cavernoma: the long-term effects of stereotactic radiosurgery","fulltext":[{"header":"Introduction","content":"\u003cp\u003eArteriovenous malformations (AVMs) are complex cerebrovascular malformations characterized by direct arterial-to-venous connections without an intervening capillary network, leading to abnormal blood flow and an elevated risk of hemorrhage [1]. The major available treatment options include microsurgical resection, endovascular embolization and stereotactic radiosurgery, which can be used independently or in combination depending on the malformation\u0026rsquo;s characteristics and location.\u003c/p\u003e \u003cp\u003eRadiosurgery, while effective in occluding AVMs by promoting vascular damage and thrombosis, can induce delayed adverse effects such as perilesional edema, cyst formation and, in rare cases, radiation-induced neoplasms or vascular proliferative lesions, including cavernomas. This case report presents a post-radiation cavernoma formation at a previously treated AVM site.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 66-year-old male presented at the neurosurgery department because he slowly developed mild anomic aphasia, decreased concentration and reduced initiative, approximately 12 years after one session of transarterial embolization follow by stereotactic radiosurgery for a partially calcified AVM. The 3.5cm wide AVM nidus was located in the pars orbitalis of the left inferior frontal gyrus. The patient presented initially in 2009 with recurring episodes of overall discomfort and presyncope, without epilepsy nor a bleeding episode. Magnetic resonance imaging (MRI) and digital subtraction angiography (DSA) identified the AVM as Spetzler-Martin grade III with a supplementary grade of 5 [1,2] (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003ea).\u003c/p\u003e \u003cp\u003eAfter multidisciplinary consultation, surgery was deemed risky because of the high supplemented Spetzler-Martin grade and the language tasks proximity visualized on the pre-treatment functional MRI (fMRI). Therefore, a treatment with endovascular embolization, followed by stereotactic radiosurgery (SRS) was initiated. The size of the nidus could be reduced to 15% via ethylene-vinyl alcohol copolymer (Onyx; Medtronic, Netherlands) injection transarterially (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eb-c).\u003c/p\u003e \u003cp\u003eStereotactic radiosurgery followed and after two years, MRI showed a complete occlusion of the AVM with mild perilesional edema. The patient remained stable in the first 5 years of follow-up, after which progressive deterioration of speech and attention occurred. The annual MRI scans and two control DSA\u0026rsquo;s demonstrated occlusion of the AVM, but gradually increasing post-radiation necrosis and growing cyst formation. The last MRI of the brain demonstrated a contrast-enhancing lesion with a diameter of 2.5 cm as well as fluid-level cysts with perilesional edema in the left frontal lobe (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). Again, DSA showed no residual nidus.\u003c/p\u003e \u003cp\u003eA resection of the radionecrosis and cysts was discussed. The pre-operative fMRI revealed cortical activation of the bilateral inferior frontal gyrus during language tasks. The left inferior frontal gyrus was considered predominant. Therefore, an asleep-awake-asleep craniotomy was performed with complete resection of the contrast-enhancing lesion. Postoperatively, there was a significant reduction of edema (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). The patient and his relatives noted improved concentration and initiative, with no further word-finding difficulties. Pathological examination of the contrast-enhancing area revealed a cavernoma.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this case report, we present a rare case of a radiation-induced cavernous malformation at the site of a previously treated AVM. The patient developed clinically significant perilesional edema and cyst formation over 12 years following SRS. Surgical resection was ultimately performed, and histopathological examination revealed a cavernous hemangioma, an uncommon yet noteworthy complication.\u003c/p\u003e \u003cp\u003eThe therapeutic goal of AVM radiation is obliteration via endothelial damage, smooth muscle cell proliferation and extracellular collagen deposition. These processes eventually lead to intravascular thrombosis and progressive occlusion of the AVM [3]. However, the same mechanisms can trigger long-term adverse changes such as perilesional edema, necrosis, cyst formation and, in rare cases, neoplasia or vascular malformations. Radiation necrosis is influenced by multiple factors. The primary determinant is the radiation dose, with higher doses increasing the likelihood of necrosis. The volume of brain parenchyma exposed to intermediate or high doses (\u0026ge;\u0026thinsp;12 Gy) is particularly significant, although threshold variations exist depending on study methodologies. The total irradiated volume, the number of treated lesions and prior radiation exposure are additional contributing factors. Intrinsic radiosensitivity and lesion location also play important roles, as deeper cerebral lesions tend to be more susceptible compared to superficial ones [4]. In our case, the total irradiated volume and the location of the lesion where the most important factors predisposing to radiation necrosis.\u003c/p\u003e \u003cp\u003eRadiation-induced cavernomas are rare but well-documented complications of brain irradiation\u003csup\u003e2\u003c/sup\u003e. Their pathogenesis is multifactorial, potentially involving endothelial injury, disruption of vascular integrity and aberrant angiogenesis triggered by radiation exposure [4]. In the context of AVM radiosurgery, cavernoma formation has been reported several years post-treatment in a few cases. Motegi et al. described a cavernoma 7 years after SRS for an AVM in the right caudate nucleus [5]. Wang et al. reported a similar lesion 6 years post-SRS in the right cerebellum, while Patterson et al. noted a symptomatic cavernoma 7 years after AVM treatment, requiring surgery [6,7]. Notably, similar cases have emerged following irradiation for other intracranial pathologies, such as meningiomas. For instance, Lee et al. described a case with MRI findings resembling our own, where a cavernoma developed after stereotactic irradiation for a meningioma [8]. These similarities underscore a shared pathophysiological pathway regardless of the initial indication for radiation.\u003c/p\u003e \u003cp\u003eIn Koester et al.'s study of 248 radiation-induced cavernomas, approximately one-third of cases required surgical management [9]. The decision to intervene surgically depends on factors such as lesion size, symptomatic presentation and associated complications like perilesional edema or cyst formation. In our case, surgical resection was indicated due to the presence of clinically significant perilesional edema and persistent cysts, which complicated differential diagnosis and posed a risk for further neurological deterioration.\u003c/p\u003e \u003cp\u003eTo mitigate the risk of late radiation-induced complications, several preventive strategies can be considered. Recent advancements in embolization techniques, including transvenous approaches, have shown promising results with high curative success rates [10]. More research is needed to reduce the risk of radiation-induced complications.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case report describes a rare case of a late radiation-induced histopathological proven cavernoma after AVM treatment. The report underscores long-term monitoring and vigilance post radiotherapy. While generally effective, SRS carries the risk of delayed complications, including cavernoma formation. Advances in radiation delivery techniques are promising in reducing such outcomes. Further research into genetic predispositions and optimized treatment protocols will be crucial in mitigating these rare but impactful complications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Sources and Conflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo specific funding was received for this study. The authors declare no conflicts of interest relevant to this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Disclosures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo specific funding was received for the study. The authors declare no conflicts of interest relevant to this study. The authors declare that there are no additional disclosures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Compliance Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that the approval of an institutional review board for this work was not necessary. Informed consent was obtained from the patient included in the study. We confirm that we have read the journal\u0026rsquo;s position on issues involved in ethical publication and affirm that this work is consistent with these guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eR.B. and D.V. were responsible for the conceptualization. R.B., L.D., F.D., L.V. and D.V. collected the data. R.B., L.D. and D.V. wrote the original draft. L.D. prepared the figures, R.B. wrote the figure legends. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSpetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg. 1986; 65(4): 476-83. DOI: 10.3171/jns.1986.65.4.0476\u003c/li\u003e\n \u003cli\u003eLawton MT, Kim H, McCulloch C. et al. A supplementary grading scale for selecting patients with brain arteriovenous malformations for surgery. Neurosurgery. 2010; 66(4): 702-713. DOI: 10.1227/01.NEU.0000367555.16733.E1\u003c/li\u003e\n \u003cli\u003eTsao MN, Li YQ, Lu G. et al. Upregulation of vascular endothelial growth factor is associated with radiation-induced blood-spinal cord barrier breakdown. J Neuropathol Exp Neurol. 1999; 58(10): 1051-60. DOI: 10.1097/00005072-199910000-00003\u003c/li\u003e\n \u003cli\u003eVellayappan BA, McGranahan T, Graber J. et al. Radiation necrosis from stereotactic radiosurgery\u0026mdash;How do we mitigate? Curr Treat Options Oncol. 2021; 22(7): 57. DOI: 10.1007/s11864-021-00854-z\u003c/li\u003e\n \u003cli\u003eMotegi H, Kuroda S, Ishii N. et al. De novo formation of cavernoma after radiosurgery for adult cerebral arteriovenous malformation. Neurol Med Chir. 2008; 48(9): 397-400. DOI: 10.2176/nmc.48.397\u003c/li\u003e\n \u003cli\u003eWang X, Hui X, Liu JP. et al. Radiation-induced cavernous malformation at the site of arteriovenous malformation following gamma knife radiosurgery: Case report. Clin Neurol Neurosurg. 2012; 114(9): 1287-89. DOI: 10.1016/j.clineuro.2012.03.005\u003c/li\u003e\n \u003cli\u003ePatterson TT, McGinity M, Crownover R. et al. Remote development of symptomatic intracranial cavernous malformation after stereotactic radiosurgery. Cureus. 2022; 14(1): e21635. DOI: 10.7759/cureus.21635\u003c/li\u003e\n \u003cli\u003eLee SH, Kim KH, Lee HJ. et al. A huge radiation-induced cavernous hemangioma following stereotactic radiosurgery for meningioma: a case report. Brain Tumor Res Treat. 2022; 10(3): 190-4. DOI: 10.14791/btrt.2022.0020\u003c/li\u003e\n \u003cli\u003eKoester SW, Rhodenhiser EG, Dabrowski SJ. et al. Radiation-induced cerebral cavernous malformations: a single-center experience and systematic literature review. World Neurosurg. 2023; 179: 222-32. DOI: 10.1016/j.wneu.2023.08.036\u003c/li\u003e\n \u003cli\u003eMendes GAC, Kalani MYS, Iosif C. et al. Transvenous curative embolization of cerebral arteriovenous malformations: a prospective cohort study. Neurosurgery. 2018; 83(5): 957-64. DOI: 10.1093/neuros/nyx581\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Arteriovenous malformation, Cavernoma, Endovascular embolization, Stereotactic radiosurgery","lastPublishedDoi":"10.21203/rs.3.rs-6261419/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6261419/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eRadiation-induced cavernomas are rare but significant late complications of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs). We report the case of a 66-year-old male who developed a contrast-enhancing lesion with cystic necrosis and perilesional edema in the left frontal lobe, 12 years after SRS following transarterial embolization for a partially calcified AVM. Digital subtraction angiography showed no AVM recurrence. Due to progressive anomic aphasia, decreased concentration and reduced initiative, a surgical resection was performed. This confirmed a radiation-induced cavernoma. This case underscores the need for long-term follow-up with multimodal imaging to differentiate late radiation-induced vascular lesions from recurrent pathology. Continuous clinical assessment is crucial for timely intervention, as delayed radiation effects can impact neurological function and patient outcomes.\u003c/p\u003e","manuscriptTitle":"From AVM to cavernoma: the long-term effects of stereotactic radiosurgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-01 09:09:58","doi":"10.21203/rs.3.rs-6261419/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"87e1310d-1778-4245-a420-f76a58baee5f","owner":[],"postedDate":"April 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-15T11:08:20+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-01 09:09:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6261419","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6261419","identity":"rs-6261419","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}