Moyamoya following cranial irradiation for primary brain tumors in children. 2007

N J Ullrich, and R Robertson, and D D Kinnamon, and R M Scott, and M W Kieran, and C D Turner, and S N Chi, and L Goumnerova, and M Proctor, and N J Tarbell, and K J Marcus, and S L Pomeroy
Department of Neurology, Children's Hospital Boston, Boston, MA 02446, USA. nicole.ullrich@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.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D008297 Male Males
D009072 Moyamoya Disease A noninflammatory, progressive occlusion of the intracranial CAROTID ARTERIES and the formation of netlike collateral arteries arising from the CIRCLE OF WILLIS. Cerebral angiogram shows the puff-of-smoke (moyamoya) collaterals at the base of the brain. It is characterized by endothelial HYPERPLASIA and FIBROSIS with thickening of arterial walls. This disease primarily affects children but can also occur in adults. Cerebrovascular Moyamoya Disease,Progressive Intracranial Occlusive Arteropathy (Moyamoya),Moya-Moya Disease,Moyamoya Disease, Classic,Moyamoya Disease, Primary,Moyamoya Disease, Secondary,Moyamoya Syndrome,Classic Moyamoya Disease,Disease, Classic Moyamoya,Disease, Moya-Moya,Disease, Primary Moyamoya,Moya Moya Disease,Moyamoya Diseases, Primary,Primary Moyamoya Disease,Primary Moyamoya Diseases,Secondary Moyamoya Disease
D009456 Neurofibromatosis 1 An autosomal dominant inherited disorder (with a high frequency of spontaneous mutations) that features developmental changes in the nervous system, muscles, bones, and skin, most notably in tissue derived from the embryonic NEURAL CREST. Multiple hyperpigmented skin lesions and subcutaneous tumors are the hallmark of this disease. Peripheral and central nervous system neoplasms occur frequently, especially OPTIC NERVE GLIOMA and NEUROFIBROSARCOMA. NF1 is caused by mutations which inactivate the NF1 gene (GENES, NEUROFIBROMATOSIS 1) on chromosome 17q. The incidence of learning disabilities is also elevated in this condition. (From Adams et al., Principles of Neurology, 6th ed, pp1014-18) There is overlap of clinical features with NOONAN SYNDROME in a syndrome called neurofibromatosis-Noonan syndrome. Both the PTPN11 and NF1 gene products are involved in the SIGNAL TRANSDUCTION pathway of Ras (RAS PROTEINS). Peripheral Neurofibromatosis,Recklinghausen Disease of Nerve,von Recklinghausen Disease,Cafe-au-Lait Spots with Pulmonic Stenosis,Molluscum Fibrosum,NF1 (Neurofibromatosis 1),Neurofibromatosis I,Neurofibromatosis Type 1,Neurofibromatosis Type I,Neurofibromatosis, Peripheral Type,Neurofibromatosis, Peripheral, NF 1,Neurofibromatosis, Peripheral, NF1,Neurofibromatosis, Type 1,Neurofibromatosis, Type I,Pulmonic Stenosis with Cafe-au-Lait Spots,Recklinghausen Disease, Nerve,Recklinghausen's Disease of Nerve,Recklinghausens Disease of Nerve,Watson Syndrome,von Recklinghausen's Disease,Cafe au Lait Spots with Pulmonic Stenosis,Neurofibromatoses, Peripheral,Neurofibromatoses, Type I,Neurofibromatosis, Peripheral,Peripheral Neurofibromatoses,Pulmonic Stenosis with Cafe au Lait Spots,Syndrome, Watson,Type 1 Neurofibromatosis,Type 1, Neurofibromatosis,Type I Neurofibromatoses,Type I, Neurofibromatosis,von Recklinghausens Disease
D009897 Optic Chiasm The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. Chiasma Opticum,Optic Chiasma,Optic Decussation,Chiasm, Optic,Chiasma Opticums,Chiasma, Optic,Chiasmas, Optic,Chiasms, Optic,Decussation, Optic,Decussations, Optic,Optic Chiasmas,Optic Chiasms,Optic Decussations,Opticum, Chiasma,Opticums, Chiasma
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D011832 Radiation Injuries Harmful effects of non-experimental exposure to ionizing or non-ionizing radiation in VERTEBRATES. Radiation Sickness,Radiation Syndrome,Injuries, Radiation,Injury, Radiation,Radiation Injury,Radiation Sicknesses,Radiation Syndromes,Sickness, Radiation,Sicknesses, Radiation,Syndrome, Radiation,Syndromes, Radiation
D011878 Radiotherapy The use of IONIZING RADIATION to treat malignant NEOPLASMS and some benign conditions. Radiotherapy, Targeted,Targeted Radiotherapy,Radiation Therapy,Radiation Therapy, Targeted,Radiation Treatment,Targeted Radiation Therapy,Radiation Therapies,Radiation Therapies, Targeted,Radiation Treatments,Radiotherapies,Radiotherapies, Targeted,Targeted Radiation Therapies,Targeted Radiotherapies,Therapies, Radiation,Therapies, Targeted Radiation,Therapy, Radiation,Therapy, Targeted Radiation,Treatment, Radiation
D001900 Boston City located in Massachusetts.
D001932 Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain

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