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From the Departments of Neurology (N.J.U., S.L.P.), Radiology (R.R.), Clinical Research Program (D.D.K.), Neurosurgery (R.M.S., L.G., M.P.), and Radiation Therapy (K.J.M.), Children's Hospital Boston, Boston, MA; Pediatric Brain Tumor Program (N.J.U., R.M.S., M.W.K., C.D.T., L.G., M.P., K.J.M., S.L.P.), Dana Farber Cancer Institute, Boston, MA; Department of Radiation Oncology (N.J.T.), Massachusetts General Hospital, Boston, MA; and Division of Pediatric Clinical Research (D.D.K.), Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL.
Address correspondence and reprint requests to Dr. Nicole J. Ullrich, Department of Neurology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02446; e-mail: nicole.ullrich{at}childrens.harvard.edu
Objective: To study the risk factors for the development of moyamoya syndrome after cranial irradiation for primary brain tumors in children.
Methods: We reviewed neuroimaging studies and dosimetry data for 456 children who were treated with radiation for a primary brain tumor and who were prospectively evaluated with serial neuroimaging studies and neurologic evaluations. A total of 345 patients had both adequate neuroimaging and radiation dosimetry data for further analysis. We used survival analysis techniques to examine the relationship of clinically important variables as risk factors for the development of moyamoya over time.
Results: Overall, 12 patients (3.5%) developed evidence of moyamoya. The onset of moyamoya was more rapid for patients with neurofibromatosis type 1 (NF1) (median of 38 vs 55 months) and for patients who received >5,000 cGy of radiation (median of 42 vs 67 months). In a multiple Cox proportional hazards regression analysis controlling for age at start of radiation, each 100-cGy increase in radiation dose increased the rate of moyamoya by 7% (hazard ratio [HR] = 1.07, 95% CI: 1.02 to 1.13, p = 0.01) and the presence of NF1 increased the rate of moyamoya threefold (HR = 3.07, 95% CI: 0.90 to 10.46, p = 0.07).
Conclusions: Moyamoya syndrome is a potentially serious complication of cranial irradiation in children, particularly for those patients with tumors in close proximity to the circle of Willis, such as optic pathway glioma. Patients who received higher doses of radiation to the circle of Willis and with neurofibromatosis type 1 have increased risk of the development of moyamoya syndrome.
See also page 954
Disclosure: The authors report no conflicts of interest.
Received January 8, 2006. Accepted in final form November 27, 2006.
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Neurology 2007 68: 954.
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