Radiation-induced meningiomas, cerebral aneurysm, and multiple cavernomas 2 decades after radiotherapy for medulloblastoma: illustrative case

Abstract

BACKGROUND

Radiation therapy is a mainstay in the management of medulloblastoma. However, it carries long-term side effects including radiation-induced tumors and vasculopathies. The authors report the first case of the occurrence of radiation-induced meningiomas, an intracranial aneurysm, and multiple cavernomas in a patient with a remote history of medulloblastoma. In addition, this is only the seventh reported radiation-associated superior cerebellar artery (SCA) aneurysm, the first such aneurysm to be associated with external beam RT and the first such aneurysm to be treated with microsurgery.

OBSERVATIONS

The patient was diagnosed with medulloblastoma when he was 4 years old and underwent surgery, craniospinal irradiation, and chemotherapy. He was well until 25 years later, when he presented with headache and left-sided weakness. Cranial imaging revealed multiple meningiomas and cavernomas. He underwent surgery to excise the largest meningioma in the right frontotemporal area. Two years later, he underwent another operation for a left frontal meningioma that increased in size. Two months postexcision, he presented with a subarachnoid hemorrhage from a ruptured right SCA aneurysm and underwent clipping. He was discharged well.

LESSONS

This case highlights the importance of long-term surveillance for patients treated with radiotherapy. However, the ideal follow-up duration and frequency of screening tests have yet to be determined.

https://thejns.org/doi/10.3171/CASE25898

Radiation therapy (RT) plays an important role in the management of medulloblastoma and other intracranial tumors. Unfortunately, long-term treatment complications may occur, including radiation-induced tumors and vasculopathy.¹ Here we report the first case of the occurrence of radiation-induced meningiomas, cerebral aneurysm, and multiple cavernomas in the same patient, a 31-year-old man with a remote history of medulloblastoma. In addition, this is only the seventh reported radiation-associated superior cerebellar artery (SCA) aneurysm, the first such aneurysm to be associated with external beam RT (EBRT) and the first such aneurysm to be treated with microsurgery.

Illustrative Case

A 31-year-old man underwent ventriculoperitoneal shunt insertion and suboccipital craniotomy for excision of medulloblastoma in 1998, when he was 4 years old. He subsequently underwent adjuvant craniospinal EBRT and chemotherapy shortly after surgery. The EBRT doses were as follows: whole-brain RT of 36 Gy in 24 fractions, tumor bed boost of 14 Gy in 7 fractions, and whole-spine RT of 30 Gy in 20 fractions. There was no tumor recurrence.

Twenty-five years later, he presented with a 1-year history of headache and progressive left-sided weakness. Contrast-enhanced cranial MRI showed multiple meningiomas, the largest of which was in the right frontotemporal convexity (Fig. 1A and B). Susceptibility-weighted imaging (SWI) revealed an area of susceptibility compatible with a cavernoma in the right cerebellum (Fig. 1C) He underwent surgery to excise this tumor, and histopathological analysis showed a WHO grade 2 (atypical) meningioma. No adjuvant therapy was given. He did not follow up again until 2 years later, when repeat cranial MRI showed progression of the previously small left frontal convexity meningioma (Fig. 1D and E). SWI also showed the appearance of a new cavernoma medial to the first one (Fig. 1F), but the patient was asymptomatic from these. He underwent a third operation to excise the tumor, which was a WHO grade 1 meningioma.

FIG. 1.

Radiation-induced meningiomas and cavernomas. The patient underwent craniospinal irradiation as adjuvant treatment for medulloblastoma during childhood. He was found to have multiple meningiomas 25 years later. A and B:Contrast-enhanced cranial axial MR images showing multiple dura-based tumors compatible with meningiomas. C: Axial susceptibility-weighted image showing an area of susceptibility compatible with a cavernoma in the right cerebellum. D and E: Follow-up axial MR images obtained after 2 years showing disappearance of the previous right convexity meningioma and marked growth of the left frontal meningioma. F: Axial susceptibility-weighted image showing the appearance of a new cavernoma medial to the first one.

Two months postexcision, he complained of a sudden severe headache. Plain cranial CT scan showed a subarachnoid hemorrhage along the perimesencephalic cisterns extending to the right sylvian cistern (Fig. 2A). Cranial CT angiography was unremarkable; hence, digital subtraction angiography was performed. It showed a saccular right SCA aneurysm (Fig. 2B). The patient underwent craniotomy for aneurysm clipping via a subtemporal transtentorial approach. Intraoperatively, the aneurysm seemed to be arising from the wall of the right SCA and was superiorly and posteriorly directed (Fig. 2C and D). The surgery was unremarkable and the patient was discharged well, with no new deficits. He was advised to undergo close clinical and radiological follow-up to monitor the remaining meningiomas and cavernomas.

FIG. 2.

Radiation-associated aneurysm. A:Axial cranial CT image showing a subarachnoid hemorrhage 3 hours postictus. B:Digital subtraction angiogram showing a right SCA aneurysm (arrow). C and D: Intraoperative pictures showing the SCA aneurysm before (C) and after (D) clipping, with the main trunk of the SCA preserved.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

Medulloblastoma is the most common malignant brain tumor in childhood, constituting 20%–24% of all pediatric intracranial tumors.² Standard of care includes maximal safe resection, craniospinal irradiation, and chemotherapy, improving long-term survival rates to 60%–80 %.^2,3 Unfortunately, many pediatric brain tumor survivors are left with the long-term sequelae of RT, including neuroendocrine and cognitive impairments, radiation-induced tumors, and vasculopathy.¹

Meningiomas are the most common radiation-induced tumors. The majority are WHO grade 1, while 5%–7% are atypical.⁴ Cahan et al. established the criteria for radiation-induced tumors: 1) the tumor must occur within the irradiated field, 2) there should a sufficient latency period between irradiation and tumor development, 3) the radiation-induced tumor must have a different histology from the original tumor, and 4) the patient must not have any tumor disposition syndromes such as neurofibromatosis.⁵ For radiation-induced meningiomas in particular, the reported latency period between radiotherapy for the primary lesions and the onset of meningiomas was 22.9 ± 11.4 years.⁵ Our patient met the first three parameters of Cahan’s criteria, but the fourth could not be determined due to lack of testing. The latency of 25 years was consistent with the reported latency period.

Another radiation-induced pathology is vasculopathy, which may present as arterial occlusion, moyamoya syndrome, aneurysm formation, cavernoma, cerebral hemorrhage, necrosis, and stroke.^3,6 Radiation-associated aneurysms are extremely rare, with a mean latency of 11.3 years (range 2–21 years) between RT and aneurysm diagnosis.⁷ Unlike radiation-induced meningiomas, the diagnostic criteria for radiation-associated aneurysms is not established. Although cerebral angiography is usually not performed prior to RT,⁸ de novo formation is suggested by the presence of an aneurysm near the previously irradiated area,^7,9 the unusual distal location,⁸ and the long latency from RT.⁸ In contrast to congenital aneurysms, they originate from the arterial wall rather than a branching point,¹⁰ which may be due to vessel wall degradation caused by radiation. There is a predilection for the internal carotid and posterior circulation arteries,¹¹ which may be explained by the proximity of these vessels to skull base structures included in the irradiated field,⁷ reinforcing the hypothesis that vascular territories exposed to high-dose radiation are more susceptible to long-term structural changes from radiotherapy.⁷ Morphologically, these aneurysms may be saccular or nonsaccular.^7,12 It was found that 74.1%–88.2% of radiation-associated aneurysms were ruptured on presentation—a much higher rate compared to classic aneurysms.^11,13 This implies that radiation-related aneurysms are more fragile and prone to rupture, which must be considered during microsurgery and embolization.^11,12

SCA aneurysms by themselves are very rare, comprising only 0.3%–0.7% of all intracranial aneurysms. They usually occur due to a mycotic condition or angiitis from a systemic disease.¹⁴ To our knowledge, this is only the seventh reported radiation-associated SCA aneurysm,^{8–9,15,17–19} the first such aneurysm to be associated with EBRT, and the first such aneurysm to be treated with microsurgery.

On review of the literature (Table 1), the age of the patients with a radiation-associated SCA aneurysm ranged from 31 to 81 years, with an almost equal sex distribution. Five patients had trigeminal neuralgia as the primary pathology, and 1 had a cerebellopontine angle meningioma. All 6 were treated with either Gamma Knife or linear accelerator–based stereotactic radiosurgery. The propensity for patients with radiosurgery-treated trigeminal neuralgia to develop radiation-induced SCA aneurysms may be due to its pathophysiology: trigeminal neuralgia is caused by vascular compression of the trigeminal nerve root, most commonly by the SCA.¹⁵ During radiosurgery, a high dose of radiation is directed at the retrogasserian zone of the trigeminal nerve.^9,15,17 Since the SCA courses near or is in contact with the nerve that is being targeted,^9,17 avoidance of substantial radiation exposure is difficult.¹⁵

TABLE 1.

Radiation-induced SCA aneurysms reported in the literature

Authors & Year	Age (yrs)/Sex	Primary Pathology	Type of RT	Latency Period (yrs)	Presentation	Aneurysm Management
Kellner et al., 20148	58/F	Meningioma	GK-SRS	10	Surveillance imaging	Endovascular
Uchikawa et al., 201715	72/F	Trigeminal neuralgia	GK-SRS	9	Aneurysmal rupture	Endovascular
Chen et al., 201717	79/M	Trigeminal neuralgia	LINAC-SRS	11	Mass effect	Endovascular
Pak et al., 201818	81/M	Trigeminal neuralgia	GK-SRS	8	Mass effect	Endovascular
Dominguez et al., 20209	77/F	Trigeminal neuralgia	GK-SRS (2×)	13, 18	Aneurysmal rupture	Endovascular
Chung et al., 202119	60/M	Trigeminal neuralgia	LINAC-SRS	9	Mass effect	Endovascular
Present case	31/M	Medulloblastoma	EBRT	25	Aneurysmal rupture	Microsurgical

GK-SRS = Gamma Knife stereotactic radiosurgery; LINAC-SRS = linear accelerator–based stereotactic radiosurgery.

The latency period between radiation treatment and the development of symptoms from the SCA aneurysm ranged from 8 to 25 years. Three of the aneurysms became symptomatic due to mass effect,^17–19 2 presented with aneurysmal rupture,^9,15 and 1 was detected on routine surveillance imaging.⁸ SCA aneurysms are challenging to treat because the SCA courses near important neurovascular structures including the brainstem, oculomotor nerve, posterior cerebral artery, and vertebral-basilar system.¹⁶ Endovascular techniques such as coiling and stent-assisted procedures are widely used, but can cause coil migration and residual aneurysmal filling.¹⁶ In contrast, microsurgical clipping gives a more definitive solution since it allows direct visualization of the aneurysm and precise manipulation of the neck, which ensures complete exclusion of the aneurysm while preserving the parent vessel.¹⁶ The latter was the chosen treatment approach for our patient, unlike the first 6 cases reported, which utilized endovascular management to treat the aneurysm.

For the management of intracranial aneurysms in general, the rationale underlying the choice between open surgery and endovascular treatment is usually unclear, as there is little high-quality evidence available.²⁰ Patient-related and aneurysm-related factors, as well as physician preference, are considered in the decision-making process.²⁰ In a lower-middle-income country like the Philippines, high out-of-pocket expenses further complicate treatment selection and pose a barrier in the provision of neurosurgical care.²¹ Neurosurgical clipping is significantly less expensive than endovascular options.²² Coiling procedures may cost 1.5 times more than clipping, while flow diversion costs 1.2 times more.²² The higher total expenses associated with endovascular treatment are primarily driven by material costs such as coils, stents, and flow diverters.^22,23

For ruptured posterior circulation aneurysms, endovascular treatment is usually considered because these aneurysms are located in a deep location and surrounded by important neurovascular structures, increasing complication rates.²⁴ However, SCA aneurysms have a distinctly different anatomy that make them more favorable for microsurgery compared to other posterior circulation aneurysms.²⁵ SCA aneurysms tend to project laterally, placing them in the better visualized carotid-oculomotor triangle and orienting the surgeon along the approach trajectory; moreover, the dome usually allows separation from perforating arteries, making preservation more likely.²⁵ The angioarchitecture of the SCA aneurysm and the higher cost of endovascular treatment contributed to the decision to manage this case with open surgery.

Only a few reports have been published on radiation-induced cavernomas (RICMs). The natural history is still largely unknown, but data suggest a sixfold increased risk of hemorrhage compared to spontaneous cavernomas.²⁶ Similar to our case, RICMs are commonly asymptomatic and incidental, with a mean latency of 9.2 years (range 3–29 years).²⁶

This case illustrates the various types of long-term sequelae that may be experienced by patients who undergo RT, emphasizing the need for follow-up. The International Late Effects of Childhood Cancer Guideline Harmonization Group and the Children’s Oncology Group developed guidelines for long-term surveillance of childhood cancer survivors. These guidelines recommend periodic focused history-taking and neurological examination that range from 1- to 5-year intervals.^27,28 At present, there is insufficient evidence to support routine imaging in asymptomatic patients.^27,28

Lessons

This case highlights the importance of long-term clinical and radiological surveillance for patients treated with radiotherapy. However, the ideal follow-up duration and frequency of screening tests are yet to be determined.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Dayrit, Amasula, Legaspi. Acquisition of data: Dayrit. Analysis and interpretation of data: Dayrit, Amasula, Khu. Drafting the article: Dayrit, Khu, Legaspi. Critically revising the article: Dayrit, Nicer, Khu. Reviewed submitted version of manuscript: Dayrit, Amasula, Khu. Approved the final version of the manuscript on behalf of all authors: Dayrit. Statistical analysis: Dayrit. Administrative/technical/material support: Dayrit, Amasula, Nicer. Study supervision: Dayrit, Legaspi.

Supplemental Information

Previous Presentations

This case was previously presented as an oral presentation at the Association of Filipino Neurosurgeons (AFN) Annual Research Contest, Seda Vertis North, Quezon City, NCR, Philippines, December 3, 2025.

Correspondence

Almira A. Dayrit: College of Medicine and Philippine General Hospital, University of the Philippines Manila, Philippines. aadayrit1@up.edu.ph.