Neurological Research A Journal of Progress in Neurosurgery, Neurology and Neurosciences ISSN: 0161-6412 (Print) 1743-1328 (Online) Journal homepage: http://www.tandfonline.com/loi/yner20 Bilateral cavernous malformations resulting from cranial irradiation of a choroid plexus papilloma Steven Chang, Marc Vanefsky, Leif Havton & Gerald Silverberg To cite this article: Steven Chang, Marc Vanefsky, Leif Havton & Gerald Silverberg (1998) Bilateral cavernous malformations resulting from cranial irradiation of a choroid plexus papilloma, Neurological Research, 20:6, 529-532, DOI: 10.1080/01616412.1998.11740559 To link to this article: http://dx.doi.org/10.1080/01616412.1998.11740559 Published online: 20 Jul 2016. Submit your article to this journal View related articles Citing articles: 16 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yner20 Download by: [Columbia University Libraries] Date: 07 August 2017, At: 09:08 Case Report Bilateral cavernous malformations resulting from cranial irradiation of a choroid plexus papilloma Downloaded by [Columbia University Libraries] at 09:08 07 August 2017 Steven D. Chang, Marc A. Vanefsky, Leif A. Havton* and Gerald D. Silverberg Department of Neurosurgery, *Department of Pathology (Neuropathology), Stanford University Medical Center, Stanford, CA 94305, USA We report a case of multiple parietal cavernous malformations in a thirteen year old female who received cranial irradiation following incomplete resection of a choroid plexus papilloma. The cavernous malformations, which developed within the prior parietal radiation ports, were diagnosed nine years after the patients' radiation treatment when the patient presented with increasing frequency of seizures. Family history was negative for familial cavernous malformations. Due to the worsening frequency of seizures, the patient underwent resection of these two cavernous malformations with diagnosis confirmed by pathology. Post-operative, there was a significant reduction in seizure frequency. The origin and pathophysiology of cavernous malformations remains controversial. Cranial radiation treatment for tumors, particularly in children, may possibly lead to the development of these lesions, as occurred in this case. This is, to our knowledge, the first case of multiple cavernous malformations occurring within a previous radiation field following radiotherapy for a neoplasm. [Neural Res 1998; 20: 529-532] Keywords: Cranial irradiation; cavernous malformation; pediatric; tumor INTRODUCTION Cavernous malformations are a class of vascular malformations that are angiographically occult, but have a propensity to bleed, provoke seizures, and/or enlarge with time 1 ' . Recent literature on cavernous malformations in pediatric populations focuses on their origin, natural history, and treatment2 - 11 . While all the pediatric series are small, there appears to be a subset of children with cavernous malformation who have had previous cranial irradiation for a brain tumor. Others have proposed that the radiation resulted in the formations of these cavernous malformations2 ' 3 ' 12' 13 • We report the case of a thirteen year old female treated with cranial irradiation following a subtotal resection of a choroid plexus papilloma. She developed bilateral cavernous malformations along the path of her prior radiation ports. These cavernous malformations and the residual choroid plexus papilloma were successfully removed, with the patient retaining a stable neurologic exam. CASE REPORT , A female presented at one year of age with lethargy and emesis. Neurologic exam was notable for a bulging anterior fontanelle. The remainder of her general exam Correspondence and reprint requests to: Gerald D. Silverberg, MD, Department of Neurosurgery, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA. Accepted for publication April1998. © 1998 Forefront Publishing Group 0161-6412/98/060529-04 and all lab tests were normal. She was eval uated at an outside institution with a CT scan which showed hydrocephalus secondary to a tumor located in the trigonal region of the left lateral ventricle. No cavernous malformations were noted at th is time. The patient had a subtotal resection of the tumor perfbrmed through a left parietal craniotomy. Pathology was consistent with a choroid plexus papilloma (Figure 1). The patient improved post-operatively w ith resolution of emesis and lethargy, but had persistent hydrocephalus requiring placement of a ventriculo-peritoneal shunt. She subsequently developed seizures and was placed on anticonvulsants w ith good response. The patient was referred for cranial irradiation, and received 3600 GyE over a six week course. Her radiation was given by bilateral opposing transparietal radiation ports. She was subsequently followed with serial MRI scans every one to two years, with no reports indicating the presence of cavernous malformations. Nine years following cranial irradiation the patient developed headaches associated with an increase in seuzure frequency and presented to our institution. An MRI scan was notable for the new appearance of bilateral lesions within the parietal lobes along the path of the cranial irradiation. These had the characteristic appearance of cavernous malformations, with T1 central hyperintensity surrounded by a hemosiderin ring (Figure 2) . Family history was negative for any other members with cavernous malformations. Due to increasing Neurological Research, 1998, Volume 20, September 529 Downloaded by [Columbia University Libraries] at 09:08 07 August 2017 Cavernous malformation resulting from tumor irradiation: Steven D. Chang et al. Figure 1: Photomicrograph of the tumor reveals features of a choro id plexus papi lloma. H & E, magnification x 160 number of seizures despite adequate trials of anticonvul sants, and th e possibi lity of a futu re clin ical hemorrhage, the patient underwent resection of both of the cavernous malfo rmation s and the residual choroid plexus papilloma through two staged surgeries. Pathology confirmed cavernous malformations (Figure 3) . Currently, she remains mildly developmentally retarded with a marked decrease in her seizure frequency. DISCUSSION Figure 2: Follow-up MRI scan nine years following the patients cranial irradiation showed bilateral cavernous malformations, seen on a gadolinium enhanced axial Tl image. Residual choroid plexus papilloma is shown (arrow) 5~0 Neurological Research, 7998, Volume 20, September Cavernous malformations, originally described by Crawford and Russe l in 1956 1, were, until recently, thought to be rare in the pediatric population. The advent of new imagi ng techniques, including CT and MRI scans, led to an increase in the identification of these lesions 3- 11. Despite the better recognition of these lesions, their origins remain unc lear. In some cases, cavernous malformations are congenital, particularly in the fami lial forms and th ose les ion s occurring in young infants6' 1o,14' 15. Others have proposed that the majority of cavernous malformations in both adults and ch il dren are acqu ired 2. Several reports of cavernous malformations that developed after cranial irradiation for tu mors have been discussed 2' 3' 12' 13' 16' 17 . Ciricillo reported on a series of 37 children w ith cavernou s malformations treated over a 1 0-year period 3 . Seven of these patients had previous cranial irradiation . The average radiation dose administered was 4.9 GyE (range 2.4-7.2 GyE), the average patient age was 5.8 years (range 2- 12), and t he average t ime from crani al irrad iation to identification of the cavernous malform ation w as 6.1 years (range 1 .5- Downloaded by [Columbia University Libraries] at 09:08 07 August 2017 Cavernous malformation resulting from tumor irradiation: Steven D. Chang et al. Figure 3: Photomicrograph showing the cavernous angioma with back to back vascular channels without internal elastic lamina and without intervening neural parenchyma. EVG, magnification x 100 16). Only one of the seven patients was symptomatic (hemorrhage). Pozzati reviewed his series of 145 cavernous malformations, and focused on 18 patients with cavernous malformations that demonstrated aggressive behavior based on de novo appearance, growth, or recurrent overt bleeding 17. Three of these patients (2 children) had been previously treated with cranial irradiation for tumors; a fourth patient treated with stereotactic radiosurgery while a teenager developed a de novo cavernous malformation. Additionall y, a cavernous malformation has been implicated in a case of an apoplectic intracerebral hemorrhage that occurred 7.5 years following irradiation for a nasopharyngeal tumor 13 • In this patient, bil ateral cavernous malformations developed along the path of her radiation treatment. Previous MRI reports, obtained to follow the residual choroid plexus papilloma, failed to demonstrate any cavernous malformation. The dose of radiation received, the age of the patient, and the interval from radiation to development of both cavernous malformations all mirror those cases reported by Ciricillo. The patient, however, is to the best of our knowledge, the only reported pediatric case demonstrating the development of multiple cavernous malformations fol lowing cranial irradiation . The presence of bilateral cavernous malformations corresponding to the opposing parietal radiation ports strengthens the likelihood of de novo cavernous malformation development secondary to crani al irradiation. If chil dren are at risk of developing such malformations following radiotherapy, they may require serial MRI scans every one to two years for at least ten years to rule out the development of any cavernous malformations. Whether the frequency of cavernous malformation development is enough to warrant serial scanning of most children after radiotherapy is unknown. The pathophysiology of the development of these cavernous malformations is unclear. Some authors have proposed that radi ation induced capillary proliferation and fibrinoid necrosis of vascular walls leads to development of cavernous malformations2 . Microhemorrhages from friable, radiation-treated vessels may induce angiogenic factors resulting in vascular malformation development16' 18 . Perivascular lymphocytes, thought to have anticoagulation potential, are common within the walls of radiated vessels, and may contribute to caverno us malfo rmation growth2 . The case report of an apoplectic intracerebral hemorrhage that occurred 7.5 years following irradiation for a nasopharyngeal tumor supports these findings 13 • • Further studies are needed, as only a few pathologic rev iews have been reported. The treatment for cavernous malfo rmati ons is less controversia l, with surgery being the method of choice. Pediatric cavernou s malformation series have shown that children w ith previously undiagnosed cavernous malformations present w ith hemorrhage (27-45 %), seizures (35-45%), and progressive neurologic defic its (11-1 9%)3 ' 5 . For these reasons, comr.lete su rgical excision is the goal of treatment2 ' 1 1' 19, with the exception of les ions located in surgically inaccessible regions. Investigators have commented that radiation Neurological Research, 7998, Volume 20, September 531 Downloaded by [Columbia University Libraries] at 09:08 07 August 2017 Cavernous malformation resulting from tumor irradiation: Steven D. Chang et al. induced cavernous malformations may have a more benign clinical course, noting that seizures are much less common in this subset of patients, and hence recommend withholding surgery until symptomatic hemorrhage occurs 3 . Yet others report that the natural history of these de novo cavernous malformations are aggressive, with hemorrhages early in the clinical course 17 • In light of the persistent seizure disorder in our patient, and given prior reports of hemorrhage in these radiation-induced cavernous malformations 3 ' 13 , resection was performed. Radiosurgery is P-roposed as a treatment for cavernous malformations 20 ' 21 , but given the uncertain natural history of these lesions after radiosurger/ 2 - 25 , and the above reports of radiation induced cavernous malformations, it is not recommended for surgically accessible lesions. CONCLUSION While recent advances in imaging make cavernous malformations more common than previously thought, it appears that some cavernous malformations are acquired lesions. The present case of bilate"ral cavernous malformations along the path of cranial irradiation for the treatment of a choroid plexus papilloma provides a clear example of a likely causal relationship. 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