Child Neurology - part 8 ppsx

36. Savino PJ, Glaser JS. Pseudopapilledema versus papilledema. Int Ophthalmol Clin 1977;17:115–137. 36a.Sanders MD. Papilloedema: “the pendulum of progress.” Eye 1997;11:267–294. 37. Anmarkrud N. The value of fluorescein fundus angiography in evaluating optic disc oedema. Acta Ophthalmol 1977;55:605–615. 38. Hayreh SS. Optic disc edema in raised intracranial pressure. V. Pathogenesis. Arch Ophthalmol 1977;95: 1553–1565. 39. Gordon GS, Wallae SJ, Neal JW. Intracranial tumours during the first two years of life: presenting features. Arch Dis Child 1995;73:345–347. 40. Low NL, Correll JW, Hammill JF. Tumors of the cerebral hemispheres in children. Arch Neurol 1965;13:547–554. 41. Burton LJ, et al. Headache etiology in a pediatric emergency department. Pediatr Emerg Care 1997;13:1–4. 42. Ropper AH. Lateral displacement of the brain and level of consciousness in patients with an acute hemispheral mass. N Engl J Med 1986;314:953–958. 43. Kuttesch JF. Advances and controversies in the management of childhood brain tumors. Curr Opin Oncol 1997;9:235–240. 44. Rorke LB. Pathology of brain tumors in infants and children. In: Tindall GT, Cooper PR, Barrow DL, eds. The practice of neurosurgery. Baltimore: Williams & Wilkins, 1996:733–754. 45. Tovi M, et al. Delineation of gliomas with magnetic resonance imaging using Gd-DTPA in comparison with computed tomography and positron emission tomography. Acta Radiol 1990;31:417–429. 46. Sartor K, et al. MR imaging in infra-, para-, and retrosellar mass lesions. Neuroradiology 1987;29:19–29. 47. Knopp MV, et al. Functional neuroimaging in the assessment of CNS neoplasms. Eur Radiol 1997; 7[Suppl 5]:209–215. 48. Brant-Zawadzki M, et al. Gd-DTPA in clinical MR of the brain: 1. Intraaxial lesions. AJR Am J Roentgenol 1986;147:1223–1230. 49. Dean B, et al. Gliomas: classification with MR imaging. Radiology 1990;174:411–415. 50. Kramer ED, et al. Staging and surveillance of children with central nervous system neoplasms: recommendations of the neurology and tumor imaging committees of the Children's Cancer Group. Pediatr Neurosurg 1994;20:254–263. 51. Rydberg JN, et al. Initial clinical experience in MR imaging of the brain with a fast fluid-attenuated inversion-recovery pulse sequence. Radiology 1994;193: 173–180. 52. Tsuchiya K, Mizutani Y, Hachiya J. Preliminary evaluation of fluid-attenuated inversion-recovery MR in the diagnosis of intracranial tumors. AJR Am J Neuroradiol 1996;17:1081–1086. 53. Kizu O, et al. Application of proton chemical shift imaging in monitoring of gamma knife radiosurgery on brain tumors. Magn Reson Imaging 1998;16:197–204. 54. Mistretta CA, Crummy AB, Strother CM. Digital angiography: a perspective. Radiology 1981;139: 273–276. 55. Brody AS. New perspectives in CT and MR imaging. Neurol Clin 1991;9:273–286. 56. Merritt HH. The cerebrospinal fluid in cases of tumors of the brain. Arch Neurol Psychiatry 1935;34: 1175–1187. 57. Berg L. Hypoglycorrhachia of noninfectious origin. Diffuse meningeal neoplasia. Neurology 1953;3: 811–824. 58. Glass JP, et al. Malignant cells in cerebrospinal fluid (CSF): the meaning of a positive CSF cytology. Neurology 1979;29:1369–1375. 59. Taveras JM, Wood EH. Diagnostic neuroradiology, 2nd ed. Baltimore: Williams & Wilkins, 1976:131. 60. Weir B, Elvidge AR. Oligodendrogliomas. An analysis of 63 cases. J Neurosurg 1968;29:500–505. 61. Babcock DS, Han BK. The accuracy of high resolution, real-time ultrasonography of the head in infancy. Radiology 1981;139:665–676. 62. Janus TJ, et al. Use of [18 F ]fluorodeoxyglucose positron emission tomography in patients with primary malignant brain tumors. Ann Neurol 1993;33:540–548. 63. Glantz MJ, et al. Identification of early recurrence of primary central nervous system tumors by [18 F ]fluorodeoxyglucose positron emission tomography. Ann Neurol 1991;29:347–355. 63a.Waldrop SM, et al. Treatment of brain tumors in children is associated with abnormal MR spectroscopic ratios in brain tissue remote from the tumor site. AJNR Am J Neuroradiol 1998;19:963–70. 63b.Koutcher JA, et al. Evaluation of chemotherapy and radiation enhancement and 31P NMR spectral changes induced by biochemical modulation Cancer Invest 1997;15:111–20. 64. Kemp SS, et al. Magnetic resonance imaging of the cerebral aqueduct. Neuroradiology 1987;29:430–436. 65. Kazner E, Lanksch W, Steinhoff H. Cranial computerized tomography in the diagnosis of brain disorders in infants and children. Neuropaediatrie 1976;7:136–174. 66. Mickle JP. Neurosurgery for pediatric brain tumors. Semin Pediatr Neurol 1997;4:273–281. 67. D'Angio GJ, et al. Key problems in the management of children with brain tumors. Int J Radiat Oncol Biol Phys 1990;18:805–810. 68. Steinbok P, et al. Value of postoperative surveillance imaging in the management of children with some common brain tumors. J Neurosurg 1996;84: 726–732. 69. Buatti JM, et al. Radiotherapy for pediatric brain tumors. Semin Pediatr Neurol 1997;4:304–319. 70. Friedman WA, Bova FJ. Stereotactic radiosurgery. Contemp Neurosurg 1989;11:1–7. 71. Rabinowitz I, et al. Accuracy of radiation field alignment in clinical practice. Int J Radiat Oncol Biol Phys 1985;11:1857–1867. 72. Friedman WA, Bova FJ, Spiegelmann R. Linear accelerator radiosurgery at the University of Florida. Neurosurg Clin N Am 1992;3:141–166. 73. Auchter RM, et al. A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis. Int J Radiat Oncol Biol Phys 1996;35:27–35. 74. Lunsford LD. Contemporary management of meningiomas: radiation therapy as an adjuvant and radiosurgery as an alternative to surgical removal. J Neurosurg 1994;80:187–190. 75. Bova FJ, et al. The University of Florida frameless high-precision stereotactic radiotherapy system. Int J Radiat Oncol Biol Phys 1997;38:875–882. 76. Flickinger JC, Kondziolka D, Lunsford LD. Clinical applications of stereotactic radiosurgery. Cancer Treat Res 1998;93:283–297. 77. Benson PJ, Sung JH. Cerebral aneurysms following radiotherapy for medulloblastoma. J Neurosurg 1989;70:545–550. 78. Ball WS, Prenger EC, Ballard ET. Neurotoxicity of radio/chemotherapy in children: pathologic and MR correlation. Am J Neuroradiol 1992;13: 761–776. 79. Duffner PK, Cohen ME. The long-term effects of central nervous system therapy on children with brain tumors. Neurol Clin 1991;9:479–495. 80. Curran WJ, et al. Magnetic resonance imaging of cranial radiation lesions. Int J Radiat Oncol Biol Phys 1987;13:1093–1098. 81. Kramer JH, et al. Absence of white matter changes on magnetic resonance imaging in children treated with CNS prophylactic therapy for leukemia. Cancer 1988;61:928–930. 82. Ellenberg L, et al. Factors affecting intellectual outcome in pediatric brain tumor patients. Neurosurgery 1987;21:638–644. 83. Glauser TA, Packer RJ. Cognitive deficits in long-term survivors of childhood brain tumors. Child Nerv Syst 1991;7:2–12. 84. Armstrong C, et al. Biphasic patterns of memory deficits following moderate-dose partial-brain irradiation: neuropsychologic outcome and proposed mechanisms. J Clin Oncol 1995;13:2263–2271. 85. Duffner PK, Cohen ME, Parker MS. Prospective intellectual testing in children with brain tumors. Ann Neurol 1988;23:575–579. 86. Radcliffe J, et al. Three- and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain-radiotherapy. Ann Neurol 1992;32:551–554. 87. Cohen BH, et al. Brain tumors in children under 2 years: treatment, survival and long-term prognosis. Pediatr Neurosurg 1993;19:171–179. 88. Suc E, et al. Brain tumours under the age of three. The price of survival. A retrospective study of 20 long-term survivors. Acta Neurochir 1990;106: 93–98. 89. Jannoun L, Bloom HJG. Long-term psychological effects in children treated for intracranial tumors. Int J Radiat Oncol Biol Phys 1990;18:747–753. 90. Curnes JT, et al. MRI of radiation injury to the brain. AJR Am J Roentgenol 1986;147:119–124. 91. Zimmerman RD, et al. Periventricular hyperintensity as seen by magnetic resonance: prevalence and significance. AJR Am J Neuroradiol 1986;7:13–20. 92. Constine LS, et al. Adverse effects of brain irradiation correlated with MR and CT imaging. Int J Radiat Oncol Biol Phys 1988;15:319–330. 93. Tsuruda JS, Kortman KE, Bradley WG. Radiation effects on cerebral white matter: MR evaluations. AJR Am J Neuroradiol 1987;8:431–437. 94. Constine LS, et al. Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med 1993;328:87–94. 95. Rappaport R, Brauner R. Growth and endocrine disorders secondary to cranial irradiation. Pediatr Res 1989;25:561–567. 96. Cassady JR. Developmental toxicity: unique radiation toxicity in children which deserves study. Radiat Oncol Invest 1993;1:77–80. 97. Samaan NA, et al. Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck. Int J Radiat Oncol Biol Phys 1982;8: 1857–1867. 98. Awwad S, Gregor A. Hormonal abnormalities in survivors of primary brain tumors. Radiother Oncol 1993;27:171–172. 99. Meadows AT, et al. Second malignant neoplasms in children: an update from the Late Effects Study Group. J Clin Oncol 1985;3:532–538. 100. Malone M, Lumley H, Erdohazi M. Astrocytoma as a second malignancy in patients with acute lymphoblastic leukemia. Cancer 1986;57:1979–1985. 101. Harrison MJ, et al. Radiation-induced meningiomas: experience at the Mount Sinai Hospital and review of the literature. J Neurosurg 1991;75:564–574. 102. Ater JL, et al. MOPP chemotherapy without irradiation as primary postsurgical therapy for brain tumors in infants and young children. J Neurooncol 1997;32:243–252. 103. Walter AW, et al. Secondary brain tumors in children treated for acute lymphoblastic leukemia at St. Jude Children's Research Hospital. J Clin Oncol 1998;16:3761–3767. 104. Allen JC, et al. Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: a possible late effect of therapy. Neurology 1991;41:148–150. 105. Sheline GE. Irradiation injury of the human brain: a review of clinical experience. In: Gilbert HA, Kagan AR, eds. Radiation damage to the nervous system. New York: Raven Press, 1980:39. 106. Duffner PK, Cohen ME. Long-term consequences of CNS treatment for childhood cancer. Part II. Clinical consequences. Pediatr Neurol 1991;7:237–242. 107. Mitchell WG, et al. Stroke as a late sequela of cranial irradiation for childhood brain tumors. J Child Neurol 1991;6:128–133. 108. Shuper A, et al. “Complicated migraine-like episodes” in children following cranial irradiation and chemotherapy. Neurology 1995;45:1837–1840. 109. Duffner PK, et al. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 1993;328:1725–1731. 110. Maria BL, Drane WE, Quisling RG. Metabolic imaging in children with brain tumors. Int Pediatr 1993; 8:233–238. 111. Maria BL, et al. 201 Thallium SPECT imaging in childhood brain tumors. Pediatr Neurosurg 1994;20:11–18. 112. Maria BL, et al. Correlation between gadolinium-DTPA contrast enhancement and thallium-201 chloride uptake in pediatric brainstem gliomas. J Child Neurol 1997;12:341–348. 113. Maria BL, et al. Comparative value of thallium and glucose SPECT imaging in childhood brain tumors. Pediatr Neurol 1998;19:351–357. 114. Langer LF, Brem H, Langer R. New technologies for fighting brain disease. Technol Rev 1991;94:62. 115. Mitchell MS. Combining chemotherapy with biological response modifiers in treatment of cancer. J Natl Cancer Inst 1988;80:1445–1450. 116. Kuhl J, et al. Primary chemotherapy after surgery and delayed irradiation in children under three years of age with medulloblastoma-pilot trial of the German pediatric brain tumor study group. Med Pediatr Oncol 1992;20:387. 117. Levin VA, ed. Cancer in the nervous system. New York: Churchill Livingstone Inc, 1996. 118. Lefkowitz I, et al. Adjuvant chemotherapy of childhood posterior fossa (PF) ependymoma: craniospinal radiation with or without CCNU, vincristine (VCR) and prednisone (P). Proc Am Soc Clin Oncol 1989;8:878. 119. Kolker JD, Weichselbaum RR. Radiobiology update. In: Kornblith PL, Walker MD, eds. Advances in neuro-oncology II. Armack: Futura Publishing Co Inc, 1997. 120. Maria BL. Brain tumors: current management in child neurology. Maria BL, ed. Hamilton, Ontario, Canada: BC Decker Inc, 1999:336–341. 121. Rowinski EK, Donehower RC. Vinca alkaloids and epipodophyllotoxins. In: Perry MC, ed. The chemotherapy source book. Baltimore: Williams & Wilkins: 1992:359–383. 122. Green DM, D'Angio GJ, eds. Late effects of treatment for childhood cancer. New York: Wiley-Liss Inc, 1992. 123. Perry MC, ed. The chemotherapy source book. Baltimore: Williams & Wilkins, 1996. 124. Maria BL, Dennis M, Obonsawin M. Severe permanent encephalopathy in acute lymphoblastic leukemia. Can J Neurol Sci 1993;20:199–205. 125. Maria BL, et al. Gene therapy for neurologic disease: benchtop discoveries to bedside applications. 1. The bench. J Child Neurol 1997;12:1–12. 126. Maria BL, et al. Gene therapy for neurologic disease: benchtop discoveries to bedside applications. 2. The bedside. J Child Neurol 1997;12:77–84. 127. Maria BL, Friedman T. Gene therapy in neuro-oncology: lessons learned from pioneering studies. In: Bodensteiner JB, Maria BL, eds. Seminars in pediatric neurology. Philadelphia: WB Saunders, 1997:333–339. 127a.Kleihues P, Burger PC, Scheithauer BW. The new WHO classification of brain tumours. Brain Pathol 1993;3:255–268. 128. Burger PC, Fuller GN. Pathology—trends and pitfalls in histologic diagnosis, immunopathology, and applications of oncogene research. Neurol Clin 1991;9:249–271. 129. Vagner-Capodano AM, et al. Cytogenic studies in 45 pediatric brain tumors. Pediatr Hematol Oncol 1992;9: 223–235. 130. Bigner SH, et al. Chromosomal characteristics of childhood brain tumors. Cancer Genet Cytogenet 1997;97:125–134. 131. Russell DS, Rubinstein LJ, eds. Pathology of tumours of the nervous system, 5th ed. London: E. Arnold, 1989. 132. Gilles FH. Pediatric brain tumors: classification. In: Morantz RA, Walsh JW, eds. Brain tumors. A comprehensive text. New York: Marcel Dekker Inc, 1994:109–134. 133. Gilles FH, et al. Histologic features and observational variation in cerebellar gliomas in children. Natl Cancer Inst Monogr 1977;58:175–181. 134. Tomlinson FH, et al. The significance of atypia and histologic malignancy in pilocytic astrocytoma of the cerebellum: a clinicopathologic and flow cytometric study. J Child Neurol 1994;9:301–310. 135. Agamanolis DP, Malone JM. Chromosomal abnormalities in 47 pediatric brain tumors. Cancer Genet Cytogenet 1995;81:125–134. 136. von Deimling A, et al. Deletions on the long arm of chromosome 17 in pilocytic astrocytoma. Acta Neuropathol (Berl) 1993;86:81–85. 137. Patt S, et al. p53 gene mutations in human astrocytic brain tumors including pilocytic astrocytomas. Hum Pathol 1996;27:586–589. 138. Burger PC, Scheithauer BW. Tumors of the nervous system. In: Atlas of tumor pathology, third series, fascicle 10. Washington, DC: Armed Forces Institute of Pathology, 1994. 139. Lantos PL, Vandenberg SR, Kleihues P. Tumors of the nervous system. In: Graham DI, Lantos PL, eds. Greenfield's neuropathology, 6th ed. London: Arnold, 1997:583–879. 140. Maria BL, et al. Diffuse leptomeningeal seeding from a malignant spinal cord astrocytoma in a child with neurofibromatosis. J Neurooncol 1986;4:159–163. 141. von Deimling A, et al. Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol 1992;3:19–26. 142. Shapiro K, Katz M. The recurrent cerebellar astrocytoma. Childs Brain 1983;10:168–176. 143. Civitello LA, et al. Leptomeningeal dissemination of low-grade gliomas in childhood. Neurology 1988;38: 562–566. 144. Rubinstein LJ. Cytogenesis and differentiation of primitive central neuroepithelial tumors. J Neuropathol Exp Neurol 1972;31:7–26. 145. Rorke LB. Origin and histogenesis of medulloblastoma. In: Zeltxer PM, Pochedly C, eds. Medulloblastomas in children. New York: Praeger, 1986:14–21. 146. Schwechheimer K, Wiedenmann B, Franke WW. Synaptophysin: a reliable marker for medulloblastomas. Virchows Arch A Pathol Anat Histopathol 1987;411:53–59. 147. Molenaar WM, Trojanowski JO. Biological markers of glial and primitive tumors. In: Salcman M, ed. Neurobiology of brain tumors: concepts in neurosurgery. Vol. 4. Baltimore: Williams & Wilkins, 1991:185–210. 148. Maraziotis J, et al. Neuron-associated class III beta-tubulin isotype, retinal S-antigen, synaptophysin and glial fibrillary acidic protein in human medulloblastomas: a clinicopathological analysis of 36 cases. Acta Neuropathol 1992;84:355–363. 149. Janss AJ, et al. Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors. Ann Neurol 1996;39:481–489. 150. Cogen PH, et al. Involvement of multiple chromosome 17p loci in medulloblastoma tumorigenesis. Am J Hum Genet 1992;50:584–589. 151. Batra SK, et al. Prognostic implications of chromosome 17p deletions in human medulloblastomas. J Neurooncol 1995;24:39–45. 152. Biegel JA, et al. Evidence for a 17p tumor related locus distinct from p53 in pediatric primitive neuroectodermal tumors. Cancer Res 1992;52:3391–3395. 153. Gajjar AJ, et al. Relation of tumor-cell ploidy to survival in children with medulloblastoma. J Clin Oncol 1993;11:2211–2217. 154. del Charco JO, et al. Medulloblastoma: time-dose relationship based on a 30-year review. Int J Radiat Oncol Biol Phys 1998;42:147–154. 155. Katsetos CD, et al. Cerebellar desmoplastic medulloblastomas. A further immunohistochemical characterization of the reticulin-free pale islands. Arch Pathol Lab Med 1989;113:1019–1029. 156. Undjian S, Marinov M. Intracranial ependymomas in children. Childs Nerv Syst 1990;6:131–134. 157. Reyes-Mugica M, et al. Ependymomas in children: histologic and DNA-flow cytometric study. Pediatr Pathol 1994;14:453–466. 158. Schiffer D, et al. Histologic prognostic factors in ependymoma. Childs Nerv Syst 1991;7:177–182. 159. Rorke LB. Relationship of morphology of ependymoma in children to prognosis. Prog Exp Tumor Res 1987;30:170–174. 160. Tominaga T, et al. Anaplastic ependymomas: clinical features and tumour suppressor gene p53 analysis. Acta Neurochir (Wien) 1995;135:163–70. 161. Kepes JJ, Rubenstein LJ, Eng LF. Pleomorphic xanthoastrocytoma: a distinctive meningocerebral glioma of young subjects with relatively favorable prognosis: a study of 12 cases. Cancer 1979;44: 1839–1852. 162. Kepes J. Pleomorphic xanthoastrocytoma: the birth of a diagnosis and a concept. Brain Pathol 1993;3: 269–274. 163. Kordek R, et al. Pleomorphic xanthoastrocytoma with a gangliomatous component: an immunohistochemical and ultrastructural study. Acta Neuropathol (Berl) 1995;89:194–197. 164. Powell SZ, et al. Divergent differentiation in pleomorphic xanthoastrocytoma. Evidence for a neuronal element and possible relationship to ganglion cell tumors. Am J Surg Pathol 1996;20:80–85. 165. Paulus W et al. Molecular genetic alterations in pleomorphic xanthoastrocytoma. Acta Neuropathol (Berl) 1996;91:293–297. 166. Tonn JC, et al. Pleomorphic xanthoastrocytoma: report of six cases with special consideration of diagnostic and therapeutic pitfalls. Surg Neurol 1997;47: 162–169. 167. Wisoff JH, et al. Neurosurgical management and influence of extent of resection on survival in pediatric high-grade astrocytomas: a report on CCG-945. J Neurosurg 1993;78:344A. 168. Wolf HK, et al. Ganglioglioma: a detailed histopathological and immunohistochemical analysis of 61 cases. Acta Neuropathol (Berl) 1994;88:166–173. 169. Miller DC, Lang FF, Epstein FJ. Central nervous system gangliogliomas. Part 1: Pathology. J Neurosurg 1993;79:859–866. 170. Jay V, et al. Malignant transformation in a ganglioglioma with anaplastic neuronal and astrocytic components. Report of a case with flow cytometric and cytogenetic analysis. Cancer 1994;73:2862–2868. 171. Johnson JH Jr, et al. Clinical outcome of pediatric gangliogliomas: ninety-nine cases over 20 years. Pediatr Neurosurg 1997;27:203–207. 172. Vandenberg SR. Desmoplastic infantile ganglioglioma and desmoplastic cerebral astrocytoma of infancy. Brain Pathol 1993;3:275–281. 173. Taratuto AL, et al. Superficial cerebral astrocytoma attached to dura. Report of six cases in infants. Cancer 1984;54:2505–2512. 174. Sperner J, et al. Clinical, radiological and histological findings in desmoplastic infantile ganglioglioma. Child Nerv Syst 1994;10:458–462. 175. Daumas-Duport, C, et al. Dysembryoplastic neuroepithelial tumor: a surgically curable tumor of young patients with intractable partial seizures. Report of thirty-nine cases. Neurosurgery 1988;23:545–556. 176. Daumas-Duport, C. Dysembryoplastic neuroepithelial tumors. Brain Pathol 1993;3:283–295. 177. Hirose T, et al. Dysembryoplastic neuroepithelial tumor (DNT): an immunohistochemical and ultrastructural study. J Neuropathol Exp Neurol 1994;53:184–195. 178. Cervera-Pierot P, et al. Dysembryoplastic neuroepithelial tumors located in the caudate nucleus area: report of four cases. Neurosurgery 1997;40:1065–1069. 179. Molloy PT, et al. Central nervous system medulloepithelioma: a series of eight cases including two arising in the pons. J Neurosurg 1996;84:430–436. 180. Rorke LB, Packer RJ, Biegel JA. Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg 1996;85:56–65. 181. Rorke LB, Packer RJ, Biegel JA. Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood. J Neurooncol 1995;24:21–28. 182. Haas JE, et al. Ultrastructure of malignancy rhabdoid tumor of the kidney. A distinctive renal tumor of children. Hum Pathol 1981;12:646–657. 183. Biegel JA, et al. Molecular analysis of a partial deletion of 22q in a central nervous system rhabdoid tumor. Genes Chromosomes Cancer 1992;5:104–108. 184. Yachnis AT, et al. Characterization of a primary central nervous system atypical teratoid/rhabdoid tumor and derivative cell line: immunophenotype and neoplastic properties. J Neuropathol Exp Neurol 1998;57:961–971. 185. Smirniotopoulos JG, Chiechi MV. Teratomas, dermoids, and epidermoids of the head and neck. Radiographics 1995;15:1437–1455. 186. Gormley WB, et al. Craniocerebral epidermoid and dermoid tumours: a review of 32 cases. Acta Neurochir 1994;128:115–121. 187. Mackenzie IR. Central neurocytoma: histologic atypia, proliferation potential, and clinical outcome. Cancer 1999;85:1606–1610. 188. Cushing H. Experiences with the cerebellar astrocytomas. Surg Gynecol Obstet 1931;52:129–204. 189. Park TS, et al. Medulloblastoma: clinical presentation and management. Experience at the Hospital for Sick Children, Toronto, 1950–1980. J Neurosurg 1983;58: 543–552. 190. Diebler C, Dulac O. Pediatric neurology and neuroradiology. Berlin: Springer-Verlag, 1987:296. 191. Stewart TG, Holmes G. Symptomatology of cerebellar tumours: a study of forty cases. Brain 1904;27: 522–591. 192. Welchman JM. Computerized tomography of intracranial tuberculomata. Clin Radiol 1979;30: 567–573. 193. Komiyama M, et al. MR imaging: possibility of tissue characterization of brain tumors using T1 and T2 values. Am J Neuroradiol 1987;8:65–70. 194. Stack JP, et al. Gadolinium-DTPA as a contrast agent in magnetic resonance imaging of the brain. Neuroradiology 1988;30:145–154. 195. Zimmerman RD, Bilaniuk LT, Rebsamen S. Magnetic resonance imaging of pediatric posterior fossa tumors. Pediatr Neurosurg 1992;18:58–64. 196. O'Reilly G, Hayward RD, Harkness WF. Myelography in the assessment of children with medulloblastoma. Br J Neurosurg 1993;7:183–188. 197. Grant FC. Cerebellar symptoms produced by supratentorial tumors: further report. Arch Neurol Psychiatry 1928;20:292–308. 198. Lhermitte J, Duclos P. Sur un ganglioneurome diffus du cortex du cervelet. Bull Assoc Franc Cancer 1920;9:99107. 199. Padberg GW, et al. Lhermitte-Duclos disease and Cowden disease: a single phakomatosis. Ann Neurol 1991;29:517–523. 200. Hair LS, et al. Immunohistochemistry and proliferative activity in Lhermitte-Duclos disease. Acta Neuropathol (Berl) 1992;84:570–573. 201. Koch R, et al. Lhermitte-Duclos disease as a component of Cowden's syndrome. Case report and review of the literature. J Neurosurg 1999;90: 776–779. 202. Sutphen R et al. Severe Lhermitte-Duclos disease with unique germline mutation of PTEN. Am J Med Genet 1999;82:290–293. 203. Matson DD. Cerebellar astrocytomas in childhood. Pediatrics 1956;18:150–158. 204. Warnick RE, Edwards MS. Pediatric brain tumors. Curr Probl Pediatr 1991;21:129–173. 205. Schneider JH, Raffel C, McComb JG. Benign cerebellar astrocytomas of childhood. Neurosurgery 1992;30:58–63. 206. Bloom HJ, Glees J, Bell J. The treatment and long-term prognosis of children with intracranial tumors: a study of 610 cases, 1950 to 1981. Int J Radiat Oncol Biol Phys 1990;18:723–745. 207. Wallner KE, et al. Treatment results of juvenile pilocytic astrocytoma. J Neurosurg 1988;69: 171–176. 208. Collins VP, Loeffler RK, Tivey H. Observations on growth rates of human tumors. AJR Am J Roentgenol 1956;76:988–1000. 209. Packer RJ. Chemotherapy for medulloblastoma/primitive neuroectodermal tumors of the posterior fossa. Ann Neurol 1990;28:823–828. 210. Packer RJ, et al. Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 1991;74:433–440. 211. Evans AE, et al. The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. J Neurosurg 1990;72:572–582. 212. Johnson DL, et al. Quality of long-term survival in young children with medulloblastoma. J Neurosurg 1994;80:1004–1010. 213. Duffner PK, et al. Second malignancies in young children with primary brain tumors following treatment with prolonged postoperative chemotherapy and delayed irradiation: a Pediatric Oncology Group study. Ann Neurol 1998;44:313–316. 214. Levin VA, et al. Treatment of medulloblastoma with procarbazine, hydroxyurea, and reduced radiation doses to whole brain and spine. J Neurosurg 1988;68: 383–387. 215. Tait DM, et al. Adjuvant chemotherapy for medulloblastoma: the first multicentre control trial of the international Society of Pediatric Oncology (SIOP 1). Eur J Cancer 1990;26:464–469. 216. Krischer JP, et al. Nitrogen mustard, vincristine, procarbazine, and prednisone as adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 1991:74;905-909. 217. Prayson RA, Fischler DF. Cerebrospinal fluid cytology. An 11-year experience with 5951 specimens. Arch Pathol Lab Med 1998;122:47-51. 218. Salazar OM. Primary malignant cerebellar astrocytomas in children: a signal for postoperative craniospinal irradiation. Int J Radiat Oncol Biol Phys 1981;7:1661–1665. 219. Keene DL, Hsu E, Ventureyra E. Brain tumors in childhood and adolescence. Pediatr Neurol 1999;20: 198–203. 220. Jayawickreme DP, Hayward RD, Harkness WF. Intracranial ependymomas in childhood: a report of 24 cases followed for 5 years. Childs Nerv Syst 1995;11:409–413. 221. Undjian S, Marinov M. Intracranial ependymomas in children. Childs Nerv Syst 1990;6:131–134. 222. Furie DM, Provenzale JM. Supratentorial ependymomas and subependymomas: CT and MR appearance. J Comput Assist Tomogr 1995;19:518–526. 223. Palma L, Celli P, Cantore G. Supratentorial ependymomas of the first two decades of life. Long-term follow-up of 20 cases (including two subependymomas). Neurosurgery 1993;32:169–175. 224. Ernestus RI, et al. Prognostic relevance of localization and grading in intracranial ependymomas of childhood. Childs Nerv Syst 1996;12:522–526. 225. Lyons MK, Kelly PJ. Posterior fossa ependymomas: report of 30 cases and review of the literature. Neurosurgery 1991;28:659–664. 226. Rousseau P, et al. Treatment of intracranial ependymomas of children: review of a 15-year experience. Int J Radiat Oncol Biol Phys 1994;28:381–386. 227. McLaughlin MP, et al. Ependymoma: results, prognostic factors, and treatment recommendations. Int J Rad Oncol Biol Phys 1998;40:845–850. 228. Lefkowitz I, et al. Adjuvant chemotherapy of childhood ependymomas with or without CCNU, vincristine, and prednisone. Pediatr Neurosci 1989;14:149. 229. Geyer JR, et al. Survival of infants with primitive neuroectodermal tumors or malignant ependymomas of the CNS treated with eight drugs in 1 day: a report from the children's cancer group. J Clin Oncol 1994;12:1607–1615. 230. Duffner PK, et al. Prognostic factors in infants and very young children with intracranial ependymomas. Pediatr Neurosurg 1998;28:215–222. 231. Chiu JK, et al. Intracranial ependymoma in children: analysis of prognostic factors. J Neurooncol 1992;13: 283–290. 232. Zorlu AF, et al. Intracranial ependymomas: treatment results and prognostic factors. Radiat Med 1994;12: 269–272. 232a.van Mourik M, et al. Complex orofacial movements and the disappearance of cerebellar mutism: report of five cases. Dev Med Child Neurol 1997;39:686–690. 232b.Dailey AT, McKhann GM, Berger MS. The pathophysiology of oral pharyngeal apraxia and mutism following posterior fossa tumor resection in children. J Neurosurg 1995;83:467–475. 232c.Liu GT, et al. Visual impairment associated with mutism after posterior fossa surgery in children. Neurosurgery 1998;42:253–256. 233. Maria BL, et al. Brainstem glioma: I. Pathology, clinical features, and therapy. J Child Neurol 1993;8:112–128. 234. Mantravardi RVP, et al. Brainstem glioma: an autopsy study of 25 cases. Cancer 1982;49:1294–1296. 235. Berger MS, et al. Pediatric brain stem tumors: radiographic, pathological and clinical correlations. Neurosurgery 1983;12:298–302. 236. Stroink AR, et al. Diagnosis and management of pediatric brain-stem gliomas. J Neurosurg 1986;65:745–750. 237. Louis DN, et al. Molecular genetics of pediatric brain stem gliomas. Application of PCR techniques to small and archival brain tumor specimens. J Neuropathol Exp Neurol 1993;52:507–515. 238. Louis DN, et al. Molecular genetics of pediatric brain stem gliomas. Application of PCR techniques to small and archival brain tumor specimens. J Neuropathol Exp Neurol 1993;52:507–515. 239. Bray PF, Carter S, Taveras JM. Brainstem tumors in children. Neurology 1958;8:17. 240. Flores LE, et al. Delay in the diagnosis of pediatric brain tumors. Am J Dis Child 1986;140:684–686. 241. Cohen ME, et al. Prognostic factors in brainstem gliomas. Neurology 1986;36:602–605. 242. Panitch HS, Berg BO. Brain stem tumors of childhood and adolescence. Am J Dis Child 1970;119: 465–472. 243. Stroink AR, et al. Transependymal benign dorsally exophytic brain stem gliomas in childhood: diagnosis and treatment recommendations. Neurosurgery 1987;20:439–444. 244. Packer RJL. Brainstem gliomas of childhood: Magnetic resonance imaging. Neurology 1985;35:397–401. 245. Barkovich AJ, et al. Brainstem gliomas: a classification based on magnetic resonance imaging. Pediatr Neurosurg 1990;16:73–83. 246. Nelson MD Jr, Soni D, Baram TZ. Necrosis in pontine gliomas: radiation induced or natural history? Radiology 1994;191:279–282. 247. Schain RJ, Wilson G. Brain stem encephalitis with radiographic evidence of medullary enlargement. Neurology 1971;21:537–539. 248. Albright AL, et al. Prognostic factors in pediatric brain-stem gliomas. J Neurosurg 1986;65:751–755. 249. Albright AL, et al. Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the Children's Cancer Group. Neurosurgery 1993;33:1026–1029. 250. Edwards MS, Levin VA, Wilson CB. Chemotherapy of pediatric posterior fossa tumors. Childs Brain 1980;7:252–260. 251. Wilson CB. Diagnosis and treatment of childhood brain tumors. Cancer 1975;35:950–956. 252. Edwards MSB, et al. Hyperfractionated radiation therapy for brain-stem gliomas: A phase I–II trial. J Neurosurg 1989;70:691–700. 253. Freeman CR, et al. Hyperfractionated radiation therapy in brain stem tumors. Cancer 1991;68:474–481. 254. Finlay JL, et al. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. J Clin Oncol 1995;13:112–123. 255. Zeltzer PM, et al. Prolonged response to carboplatin in an infant with brainstem glioma. Cancer 1991;67: 43–47. 256. Gaynon PS, et al. Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial. Cancer 1990;66:2465–2469. 257. Allen JC, Helson L. High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children. Am J Pediatr Hematol Oncol 1990;112:297–300. 258. Kedar A, et al. High-dose chemotherapy with marrow reinfusion and hyperfractionated irradiation for children with brainstem glioma. Proc Am Soc Clin Oncol 1994;177:428–436. 259. Krestchmar CS, et al. Pre-irradiation chemotherapy and hyperfractionated radiation therapy 66 Gy for children with brain stem tumors: a phase II study of the Pediatric Oncology Group Protocol 8833. Cancer 1993;72:1404–1413. 259a.Chuba PJ, et al. Permanent I-125 brain stem implants in children. Childs Nerv Syst 1998;14:570–577. 259b.Culver KW, et al. In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 1992;256:1550–1552. 259c.Fueyo J, et al. Targeting in gene therapy for gliomas. Arch Neurol 1999;56:445–448. 260. Richmond IL, Wilson CB. Parasellar tumors in children. I. Clinical presentation, preoperative assessment, and differential diagnosis. Childs Brain 1980;7:73–84. 260a.Crotty TB, et al. Papillary craniopharyngioma: a clinicopathological study of 48 cases. J Neurosurg 1995;83:206–214. 261. Liszczak T, et al. Morphological, biochemical, ultrastructural, tissue culture and clinical observations of typical and aggressive craniopharyngiomas. Acta Neuropathol 1978;43:191–203. 262. Northfield DWC. Rathke-pouch tumours. Brain 1957;80:293–312. 263. Epstein F, McCleary EL. Intrinsic brain-stem tumors of childhood. Surgical indications. J Neurosurg 1986;64:11–15. 264. Bingas B, Wolter M. Das Kraniopharyngiom. Fortschr Neurol Psychiatr 1968;36:117–195. 265. Imura H, Kato Y, Nakai Y. Endocrine aspects of tumors arising from suprasellar, third ventricular regions. Prog Exp Tumor Res 1987;30:313–324. 266. Newman CB, Levine LS, New MI. Endocrine function in children with intrasellar and suprasellar neoplasms. Am J Dis Child 1981;135:259–262. 267. Cacciari E, et al. How many cases of true precocious puberty are idiopathic? J Pediatr 1983;102:357–360. 268. Bailey P. Concerning the cerebellar symptoms produced by suprasellar tumors. Arch Neurol Psychiatry 1924;11:137–150. 269. Ito H, et al. Preoperative diagnosis of Rathke's cleft cyst. Childs Nerv Syst 1987;3:225–227. 270. Brummitt ML, Kline LB, Wilson ER. Craniopharyngioma: pitfalls in diagnosis. J Clin Neuroophthalmol 1992;12:77–81. 271. Russell RWR, Pennybacker JB. Craniopharyngioma in the elderly. J Neurol Neurosurg Psychiatry 1961; 24:1–13. 272. Watkins L, et al. Skull base chordomas: a review of 38 patients, 1958–1988. Br J Neurosurg 1993;7:241–248. 273. Kaneko Y, et al. Chordoma in early childhood: a clinicopathological study. Neurosurgery 1991;29: 442–446. 274. Matsumoto J, Towbin RB, Ball WS. Cranial chordomas in infancy and childhood: a report of two cases and review of the literature. Pediatr Radiol 1989;20: 28–32. 275. Hoffman HJ, et al. Investigation and management of suprasellar arachnoid cysts. J Neurosurg 1982;57: 597–602. 276. Nellhaus G. The bobble-head doll syndrome. A “tic” with a neuropathologic basis. Pediatrics 1967;40: 250–253. 277. Russell A. A diencephalic syndrome of emaciation in infancy and childhood [Abstract]. Arch Dis Child 1951;26:2–74. 278. Shillito J. Treatment of craniopharyngioma. Clin Neurosurg 1986;33:533–546. 279. Yasargil MG, et al. Total removal of craniopharyngiomas. Approaches and long-term results in 144 patients. J Neurosurg 1990;73:3–11. 280. Jose CC, et al. Radiotherapy for the treatment of recurrent craniopharyngioma. Clin Oncol (R Coll Radiol) 1992;5:287–289. 281. Rajan B, et al. Craniopharyngioma—long-term results following limited surgery and radiotherapy. Radiother Oncol 1993;26:1–10. 282. Regine WF, Kramer S. Pediatric craniopharyngiomas: long-term results of combined treatment with surgery and radiation. Int J Radiation Oncology Biol Phys 1992;24:611–617. 283. Hoffman HJ. Craniopharyngiomas. Can J Neurol Sci 1985;12:348–352. 284. de Vile CJ, et al. Management of childhood craniopharyngioma: can the morbidity of radical surgery be predicted? J Neurosurg 1996;85:73–81. 285. Fisher PG, et al. Outcomes and failure patterns in childhood craniopharyngiomas. Childs Nerv Syst 1998;14:558–563. 286. Richmond IL, Wilson CB. Parasellar tumors in children. II. Surgical management, radiation therapy and follow-up. Childs Brain 1980;7:85–94. 287. Bernstein M, Laperriere NJ. A critical appraisal of brachytherapy for pediatric brain tumors. Pediatr Neurosurg 1990–91;16:213–218. 288. Van den Berge JH, et al. Intracavitary brachytherapy of cystic craniopharyngiomas. J Neurosurg 1992;77: 545–550. 289. Backlund EO. Colloidal radioisotopes as part of a multi-modality treatment of craniopharyngiomas. J Neurol Sci 1989;33:95–97. 290. Lyen KR, Grant DB. Endocrine function, morbidity and mortality after surgery for craniopharyngioma. Arch Dis Child 1982;57:837–841. 291. Honegger J, Buchfelder M, Fahlbusch R. Surgical treatment of craniopharyngiomas: endocrinological results. J Neurosurg 1999;90:251–257. 292. de Vile CJ, et al. Obesity in childhood craniopharyngioma: relation to post-operative hypothalamic damage shown by magnetic resonance imaging. J Clin Endocrin Metab 1996;81:2734–2737. 292a.Fahlbusch R, et al. Surgical treatment of craniopharyngiomas: experience with 168 patients. J Neurosurg 1999;90:237–250. 293. Anderson CA, et al. Neurobehavioral outcome in pediatric craniopharyngioma. Pediatr Neurosurg 1997;26:255–260. 294. Martin P, Cushing H. Primary gliomas of chiasm and optic nerves in their intracranial portion. Arch Ophthalmol 1923;52:209–241. 295. Imes RK, Hoyt WF. Childhood chiasmal gliomas. Update on the fate of patients in the 1969 San Francisco study. Prog Exp Tumor Res 1987;30:108–112. 296. Listernick R, Charrow J. Neurofibromatosis type 1 in childhood. J Pediatr 1990;116:845–853. 297. Chutorian AM, et al. Optic gliomas in children. Neurology 1964;14:83–95. 298. Iraci G, et al. Gliomas of the optic nerve and chiasm: a clinical review. Childs Brain 1981;8:326–349. 299. Lindblom B, Truwit CL, Hoyt WF. Optic nerve sheath meningioma. Definition of intraorbital, intracanalicular, and intracranial components with magnetic resonance imaging. Ophthalmology 1992;99:560–566. 300. Dunn DW, Purvin V. Optic pathway gliomas in neurofibromatosis. Dev Med Child Neurol 1990;32:820–824. 301. Hoffman HJ, et al. Optic pathway/hypothalamic gliomas: a dilemma in management. Pediatr Neurosurg 1993;19:186–195. 302. Alvord EC, Lofton S. Gliomas of the optic nerve or chiasm. J Neurosurg 1988;68:85–98. 303. Tao ML, et al. Childhood optic chasm gliomas: radio-graphic response following radiotherapy and long-term clinical outcome. Int J Radiat Oncol Biol Phys 1997;39:579–587. 304. Tenny RT, et al. The neurosurgical management of optic glioma. Results in 104 patients. J Neurosurg 1982;57:452–458. 305. Jenkin D, et al. Optic glioma in childhood. Resection, irradiation or surveillance? The University of Toronto experience [Abstract]. Pediatic Neurosurg 1990–91; 16:1–27. 306. Packer RJ, et al. Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update. Ann Neurol 1988;23:79–85. 307. Petronio J, et al. Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. J Neurosurg 1991;74:701–708. 308. Packer RJ, et al. Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol 1993;11:850–856. 309. Chamberlain MC, Grafe MR. Recurrent chiasmatic-hypothalamic glioma treated with oral etoposide. J Clin Oncol 1995;13:2072–2076. 310. Vaquero J, Ramiro J, Martínez R. Clinicopathological experience with pineocytomas: report of five surgically treated cases. Neurosurgery 1990;27: 618–619. 311. Edwards MSB, Hudgins RJ, Wilson CB. Pineal region tumors in children. J Neurosurg 1988;68: 689–696. 312. Russell WO, Sachs E. Pinealoma: a clinicopathologic study of seven cases with a review of the literature. Arch Pathol 1943;35:869–888. 313. Jooma R, Kendall BE. Diagnosis and management of pineal tumors. J Neurosurg 1983;58:654–665. 314. Hoffman HJ, et al. Experience with pineal region tumors in childhood. Neurol Res 1984;6:107–112. 315. Schild SE, et al. Pineal parenchymal tumors: clinical, pathologic, and therapeutic aspects. Cancer 1994;72: 870–880. 316. Bodensteiner JB, et al. Incidental pineal cysts in a prospectively ascertain normal cohort. Clin Pediatr 1996;35:277–279. 317. Stein BM, Bruce JN. Surgical management of pineal region tumors. Clin Neurosurg 1992;39:509–532. 318. Hiraga S, et al. A study of 31 juvenile patients with primary intracranial germ cell tumor [Abstract]. Pediatr Neurosurg 1990–91;16:1–18. 319. Kageyama, N, et al. Intracranial germinal tumors. Prog Exp Tumor Res 1987;30:255–267. 320. Posner M, Horrax G. Eye signs in pineal tumors. J Neurosurg 1946;3:15–24. 321. Pesin SR, Shields JA. Seven cases of trilateral retinoblastoma. Am J Ophthalmol 1989;107:121–126. 322. Zimmerman RA. Computed tomography on pineal, parapineal and histologically related tumors. Radiology 1980;137:669–677. 323. Ganti SR, et al. CT of pineal region tumors. Am J Neuroradiol 1986;7:97–104. 324. Hoffman HJ. Pineal region tumors. Prog Exp Tumor Res 1987;30:281–288. 325. Edwards MSB, Hudgins RJ, Wilson CB. Pineal region tumors in children. J Neurosurg 1988;68:689–696. 326. Vaquero J, Ramiro J, Martínez R. Clinicopathological experience with pineocytomas: report of five surgically treated cases. Neurosurgery 1990;27: 618–619. 327. Lapras C, et al. Direct surgery for pineal tumors: Occipital-transtentorial approach. Prog Exp Tumor Res 1987;30:268–280. 328. Packer RJ, et al. Choroid plexus carcinoma of childhood. Cancer 1992;69:580–585. 329. Pierga JY, et al. Carcinoma of the choroid plexus: a pediatric experience. Med Pediatr Oncol 1993;21:480–487. 330. Zwetsloot CP, Kros JM, Pay y Gueze HD. Familial occurrence of tumors of the choroid plexus. J Med Genet 1991;28:492–494. 331. Trifiletti RR, et al. Aicardi syndrome with multiple tumors: a case report with literature review. Brain Dev 1995;17:283–285. 332. Johnson DL. Management of choroid plexus tumors in children. Pediatr Neurosci 1989;15:195–206. 333. Maria BL, et al. Response of a recurrent choroid plexus tumor to combination chemotherapy. J Neurooncol 1985;3:259–262. 334. Mathiesen T, et al. Third ventricle colloid cysts: a consecutive 12-year series. J Neurosurg 1997;86:5–12. 335. Macaulay RJ, et al. Histological and ultrastructural analysis of six colloid cysts in children. Acta Neuropathol 1997;93:271–276. 336. Teng P, Papatheodorou C. Tumors of cerebral ventricles in children. J Nerv Ment Dis 1966;142:87–93. 337. Antunes JL, Louis KM, Ganti SR. Colloid cysts of the third ventricle. Neurosurgery 1980;7:450–455. 338. McMackin D, et al. Correlation of fornix damage with memory impairment in six cases of colloid cyst removal. Acta Neurochir 1995;13:12–18. 339. Styne DM, et al. Treatment of Cushing's disease in childhood and adolescence by transsphenoidal microadenomectomy. N Engl J Med 1984;310:889–893. 340. Kanter SL, et al. Pituitary adenomas in pediatric patients: are they more invasive? Pediatr Neurosci 1985;12:202–204. 341. Gjerris F. Clinical aspects and long-term prognosis in supratentorial tumors in infancy and childhood. Acta Neurol Scand 1978;57:445–470. 342. Reifenberger J, et al. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19p and 1p. Am J Pathol 1994;145: 1175–1190. 343. Kraus JA, et al. Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma. J Neuropathol Exp Neurol 1995;54:91–95. 344. Sutton LN, et al. Cerebral gangliogliomas of childhood. Prog Exp Tumor Res 1987;30:239–246. 345. Wolf HK, et al. Ganglioglioma: a detailed histopathological and immunohistochemical analysis of 61 cases. Acta Neuropathol (Berl) 1994;88:166–173. 346. Miller DC, Lang FF, Epstein FJ. Central nervous system gangliogliomas. Part 1. Pathology. J Neurosurg 1993;79:859–866. 347. Jay V, et al. Malignant transformation in a ganglioglioma with anaplastic neuronal and astrocytic components. Report of a case with flow cytometric and cytogenetic analysis. Cancer 1994;73:2862–2868. 348. Cooper M, Dohn DF. Intracranial meningiomas in childhood. Cleve Clin Quart 1974;41:197–204. 349. Merten DF, et al. Meningiomas of childhood and adolescence. J Pediatr 1974;84:696–700. 350. Howe JG, Gibson JD. Uncinate seizures and tumors, a myth reexamined. Ann Neurol 1982;12:2–27. 351. Page LK, Lombroso CT, Matson DD. Childhood epilepsy with late detection of cerebral glioma. J Neurosurg 1969;31:253–261. 352. Blume WT, Girvin JP, Kaufmann JCE. Childhood brain tumors presenting as chronic uncontrolled focal seizure disorders. Ann Neurol 1982;12:538–541. 353. Dropcho EJ, et al. Supratentorial malignant gliomas in childhood: a review of fifty cases. Ann Neurol 1987;22:355–364. 354. Laws ER Jr, et al. Neurosurgical management of low-grade astrocytoma of the cerebral hemispheres. J Neurosurg 1984;61:665–673. 355. Gajjar A, et al. Response of pediatric low grade gliomas to chemotherapy. Pediatr Neurosurg 1993; 19:113–120. 356. North CA, et al. Low-grade cerebral astrocytomas. Survival and quality of life after radiation therapy. Cancer 1990;66:6–14. 357. Berger MS, Ojemann GA, Lettich E. Neurophysiological monitoring during astrocytoma surgery. Neurosurg Clin N Am 1990;1:65–80. 358. Mahaley MS Jr, et al. National survey of patterns of care for brain-tumor patients. J Neurosurg 1989;71: 826–836. 359. Phuphanich S, et al. Supratentorial malignant gliomas of childhood. Results of treatment with radiation therapy and chemotherapy. J Neurosurg 1984;60:495–499. 360. Sposto R, et al. The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. J Neurooncol 1989;7:165–177. 361. Cairncross JG, Macdonald DR. Malignant oligodendroglioma: a chemosensitive tumor. Proc ASCO 1988;7:3–33. 362. Mahoney DH Jr, et al. High-dose melphalan and cyclophosphamide with autologous bone marrow rescue for recurrent/progressive malignant brain tumor in children: a pilot pediatric oncology group study. J Clin Oncol 1996;14:382–388. 363. Sneed PK, et al. Long-term follow-up after high-activity 125 I brachytherapy for pediatric brain tumors. Pediatr Neurosurg 1996;24:314–322. 364. Coffey RJ, Lunsford LD, Flickinger JC. The role of radiosurgery in the treatment of malignant brain tumors. Neurosurg Clin N Am 1992;3:231–244. 364a.Pollock BE, et al. The Mayo Clinic gamma knife experience: indications and initial results. Mayo Clin Proc 1999;74:5–13. 365. Fathallah-Shaykh H. New molecular strategies to cure brain tumors. Arch Neurol 1999;56:449–453. 366. Tomita T, McLone DG. Brain tumors during the first twenty-four months of life. Neurosurgery 1985;17: 913–919. 367. Cohen BH, et al. Brain tumors in children under 2 years: treatment, survival and long-term prognosis. Pediatr Neurosurg 1993;19:171–179. 368. Deutsch M. Radiotherapy for primary brain tumors in very young children. Cancer 1982;50:2785–2789. 369. Jooma R, Kendall BE, Hayward RD. Intracranial tumors in neonates: a report of seventeen cases. Surg Neurol 1984;21:165–170. 370. Suc E, et al. Brain tumours under the age of three. The price of survival. A retrospective study of 20 long-term survivors. Acta Neurochir (Wien) 1990;106:93–98. 371. Strauss LC, et al. Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors. Med Pediatr Oncol 1991;19:16–21. 372. Tait DM, et al. Adjuvant chemotherapy for medulloblastoma: the first multicentre control trial of the International Society of Paediatric Oncology (SIOP I). Eur J Cancer 1990;26:464–469. 373. Krischer JP, et al. Nitrogen mustard, vincristine, procarbazine, and prednisone as adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 1991;74:905–909. 374. Kovnar EH, et al. Preirradiation cisplatin and etoposide in the treatment of high-risk medulloblastoma and other malignant embryonal tumors of the central nervous system: a phase II study. J Clin Oncol 1990;8:330–336. 375. Finlay J, et al. Randomized phase III trial in childhood high-grade astrocytomas comparing vincristine, lomustine and prednisone with eight-drug-in-one-day regimen. J Clin Oncol 1995;13:112–123. 376. Maria BL. High dose chemotherapy in the treatment of children with infiltrative brain tumors. Int Pediatr 1993;8:244–249. 377. Kedar A, et al. High-dose chemotherapy with marrow reinfusion and hyperfractionated irradiation for children with high-risk brain tumors. Med Pediatr Oncol 1994;23:428–436. 378. Shen V, et al. Collection and use of peripheral blood stem cells in young children with refractory solid tumors. Bone Marrow Transplant 1997;19:197–204. 379. Pascual-Castroviejo I. Epidemiology of spinal cord tumors in children. In: Pascual-Castroviejo I, eds. International review of child neurology series: spinal tumors in children and adolescents. New York: Raven Press, 1990:1–10. 380. Di Lorenzo N, Giuffre R, Fortuna A. Primary spinal neoplasms in childhood: analysis of 1234 published cases (including 56 personal cases) by pathology, sex, age and site. Differences from the situation in adults. Neurochirurgia (Stuttg) 1982;25:153–164. 381. Arseni C, Horvath L, Iliescu D. Intraspinal tumours in children. Psychiatr Neurol Neurochir 1967;70: 123–133. 382. Stella G, et al. Benign tumors of the pediatric spine: statistical notes. Chir Organi Mov 1998;83:15–21. 383. Murovic J, Sundaresan N. Pediatric spinal axis tumors. Neurosurg Clin N Am 1992;3:947–958. 384. Pascual-Castroviejo I, ed. Spinal tumors in children and adolescents. New York: Raven Press, 1990. 385. Steinbok P, Cochrane DD, Poskitt K. Intramedullary spinal cord tumors in children. Neurosurg Clin N Am 1992;3:931–945. 386. O'Sullivan C, et al. Spinal cord tumors in children: long-term results of combined surgical and radiation treatment. J Neurosurg 1994;81:507–512. 387. Escalona-Zapata J. Epidemiology of spinal cord tumors in children. In: Pascual-Castroviejo I, eds. International review of child neurology series: spinal tumors in children and adolescents. New York: Raven Press, 1990:11–34. 388. Kwon OK, et al. Primary intramedullary spinal cord primitive neuroectodermal tumor with intracranial seeding in an infant. Childs Nerv Syst 1996;12:633–636. 389. Nam DH, et al. Intramedullary anaplastic oligodendroglioma in a child. Childs Nerv Syst 1998;14: 127–130. 390. Chadduck WM, Frederick AB, Sawyer JR. Cytogenetic studies of pediatric brain and spinal cord tumors. Pediatr Neurosurg 1991–92;17:57–65. 391. Levy WJ, Bay J, Dohn D. Spinal cord meningioma. J Neurosurg 1982;57:804–812. 392. Richardson FL. A report of 16 tumors of the spinal cord: the importance of spinal rigidity as an early sign of disease. J Pediatr 1960;57:42–54. 393. Constantini S, et al. Intramedullary spinal cord tumors in children under the age of 3 years. J Neurosurg 1996;85:1036–1043. 394. Buchanan DN. Tumors of the spinal cord in infancy [Abstract]. Arch Neurol Psychiatry 1950;63:835. 395. Haft H, Ransohoff J, Carter S. Spinal cord tumors in children. Pediatrics 1959;23:1152–1159. 396. Ross AT, Bailey OT. Tumors arising within the spinal canal in children. Neurology 1953;3:922–930. 397. Oi S, Raimondi AJ. Hydrocephalus associated with intraspinal neoplasms in childhood. Am J Dis Child 1981;135:1122–1124. 398. Rifkinson-Mann S, Wisoff JH, Epstein F. The association of hydrocephalus with intramedullary spinal cord tumors: a series of 25 patients. Neurosurgery 1990;27:749–754. 399. Innocenzi G, et al. Intramedullary astrocytomas and ependymomas in the pediatric age group: a retrospective study. Childs Nerv Syst 1996;12:776–780. 400. Bouffet E, et al. Prognostic factors in pediatric spinal cord astrocytoma. Cancer 1998;83:2391–2399. 401. Robertson PL. Atypical presentations of spinal cord tumors in children. J Child Neurol 1992;7:360–363. 402. Eeg-Olofsson O, Carlsson E, Jeppson S. Recurrent abdominal pains as the first symptom of spinal cord tumor. Acta Paediatr Scand 1981;70:595–597. 403. Taylor LJ. Painful scoliosis: a need for further investigation. BMJ 1985;292:120–122. 404. Blaser S, Harwood-Nash D. Pediatric spinal neoplasms. Top Magn Reson Imaging 1993;5:190–202. 405. Quisling RG. Imaging for pediatric brain tumors. Semin Pediatr Neurol 1997;4:254–272. 406. Epstein FJ, Farmer JP, Schneider SJ. Intraoperative ultrasonography: an important surgical adjunct for intramedullary tumors. J Neurosurg 1991;74:729–733. 407. Kothbauer K, Deletis V, Epstein FJ. Intraoperative spinal cord monitoring for intramedullary surgery: an essential adjunct. Pediatr Neurosurg 1997;26: 247–254. 408. Epstein FJ. Surgical treatment of intramedullary spinal cord tumors of childhood. In: Pascual-Castroviejo I, eds. International review of child neurology series: spinal tumors in children and adolescents. New York: Raven Press, 1990:51–70. 409. Mottl H, Koutecky J. Treatment of spinal cord tumors in children. Med Pediatr Oncol 1997;29:293–295. 410. Goh KY, Velasquez L, Epstein FJ. Pediatric intramedullary spinal cord tumors: is surgery alone enough? Pediatr Neurosurg 1997;27:34–39. 411. Godwin-Austin RB, Howell DA, Worthington B. Observations in radiation myelopathy. Brain 1975;98:557–568. 412. DiChiro G, Herdt JR. Angiographic demonstration of spinal cord arterial occlusion in post-radiation myelomalacia. Radiology 1973;106:317–319. 413. Wara WM, et al. Radiation tolerance of the spinal cord. Cancer 1975;35:1558–1562. 414. Quincke H. Ueber Meningitis serosa. Volkmann's Sammlung klinischer Vorträge. N F 1893, Nr. 67. Cited in: Quincke H. Ueber Meningitis serosa und verwandte Zustände. Deutsch Z Nervenheilk 1897;9:149–168. 415. Johnston I, Paterson A. Benign intracranial hypertension. I. Diagnosis and prognosis. Brain 1974;97: 289–300. 416. Feldman MH, Schlezinger NS. Benign intracranial hypertension associated with hypervitaminosis A. Arch Neurol 1970;22:1–7. 417. Soler D, et al. Diagnosis and management of benign intracranial hypertension. Arch Dis Child 1998;78: 89–94. 417a.Konrad D, Kuster H, Hunziker UA. Pseudotumour cerebri after varicella. Eur J Pediatr 1998;157: 904–906. 418. Walker AE, Adamkiewicz JJ. Pseudotumor cerebri associated with prolonged corticosteroid therapy: reports of four cases. JAMA 1964;188:779–784. 419. Gills JP, Kapp JP, Odom GL. Benign intracranial hypertension: pseudotumor cerebri from obstruction of dural sinuses. Arch Ophthalmol 1967;78:592–595. 420. Rush JA. Pseudotumor cerebri: clinical profile and visual outcome in 63 patients. Mayo Clin Proc 1980;55:541–546. 421. Greer M. Benign intracranial hypertension. IV. Menarche. Neurology 1964;14:569–573. 422. McComb JG. Recent research into the nature of cerebrospinal fluid formation and absorption. J Neurosurg 1983;59:369–383. 423. Moser FG, et al. MR imaging of pseudotumor cerebri. Am J Radiol 1988;4:903–909. 424. Foley J. Benign forms of intracranial hypertension—“toxic” and “otitic” hydrocephalus. Brain 1955;78: 1–41. 425. Greer M. Benign intracranial hypertension. I. Mastoiditis and lateral sinus obstruction. Neurology 1962;12:472–476. 426. Babikian P, Corbett J, Bell W. Idiopathic intracranial hypertension in children: the Iowa experience. J Child Neurol 1994;9:144–149. 427. Speer C, et al. Fourth cranial nerve palsy in pediatric patients with pseudotumor cerebri. Am J Ophthalmol 1999;127:236–237. 428. Jacobson DM, et al. Computed tomography ventricular size has no predictive value in diagnosing pseudotumor cerebri. Neurology 1990;40: 1454–1455. 429. Rosenberg ML, et al. Cerebrospinal fluid diversion procedures in pseudotumor cerebri. Neurology 1993;43:1071–1072. 430. Corbett JJ, Thompson HS. The rational management of idiopathic intracranial hypertension. Arch Neurol 1989;46:1049–1051. 431. Baker RS, Baumann RJ, Buncic JR. Idiopathic intracranial hypertension (pseudotumor cerebri) in pediatric patients. Pediatr Neurol 1989;5:5–11. 432. Grant DN. Benign intracranial hypertension. A review of 79 cases in infancy and childhood. Arch Dis Child 1971;46:651–655. 433. Guidetti B, Giuffre R, Gambacorta D. Follow-up study of 100 cases of pseudotumor cerebri. Acta Neurochir 1968;18:259–267. 434. Corbett JJ, et al. Visual loss in pseudotumor cerebri. Follow up of 57 patients from 5 to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol 1982;39:461–474. Chapter 11 Neurocutaneous Syndromes Child Neurology Chapter 11 Neurocutaneous Syndromes John H. Menkes and R Bernard L. Maria Departments of Neurology and Pediatrics, University of California, Los Angeles, UCLA School of Medicine, and Department of Pediatric Neurology, Cedars-Sinai Medical Center, Los Angeles, California 90048; and R Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida 32610 Neurofibromatosis (Von Recklinghausen Disease) Neurofibromatosis 1 Neurofibromatosis 2 Tuberous Sclerosis Sturge-Weber Syndrome Von Hippel–Lindau Disease Ataxia-Telangiectasia Incontinentia Pigmenti and Hypomelanosis of Ito Chapter References The neurocutaneous syndromes are marked by the conjoined abnormalities of skin and nervous system. The term phakomatoses (phakomatosis from fkos, Greek for lentil) is reserved for a group of diseases in which the subject is predisposed to tumors of the skin, nervous system, and other organs. The major entities included among the phakomatoses are the neurofibromatoses, tuberous sclerosis (TS), Sturge-Weber syndrome (SWS), von Hippel–Lindau disease, and ataxia-telangiectasia (AT). Additionally, numerous other conditions exist, many of uncertain heredity and some extremely rare, in which abnormalities of skin are linked with those of the nervous system. These are detailed in a book edited by Gomez (1). NEUROFIBROMATOSIS (VON RECKLINGHAUSEN DISEASE) No longer considered to be a single disorder, neurofibromatosis has been divided into at least two genetically distinct forms. The common form, once known as peripheral neurofibromatosis, is called neurofibromatosis 1 (NF1). The other, rarer form, once termed central neurofibromatosis, is now called neurofibromatosis 2 (NF2). Additionally, several authorities distinguish segmental neurofibromatosis, in which the features of NF1 are confined to one part of the body, spinal neurofibromatosis, characterized by the late appearance of spinal cord tumors, and a condition marked by autosomal dominant café au lait spots. Neurofibromatosis 1 NF1 is characterized by multiple tumors within the central and peripheral nervous systems, cutaneous pigmentation, and lesions of the vascular system and viscera. Additionally, a tendency exists for a variety of tissues to undergo malignant transformation. Although it was described initially in the eighteenth century, and more succinctly in 1849 by Smith (2), von Recklinghausen in 1882 first combined the various features of the condition and termed it neurofibromatosis (3). The disease occurs in approximately 1 in 3,000 live births and is transmitted as a dominant trait with variable expression but virtually complete penetrance by the age of 5 years (4). It is the most common single-gene defect to affect the nervous system. Approximately one-half of the cases appear to be sporadic, and the mutation rate has been estimated at 1 in 10,000 gametes per generation, one of the highest mutation rates in humans ( 5). Stephens and coworkers found that 93% of new mutations were in the paternally derived chromosome (6). For as yet unknown reasons, no parental age effect occurs. As determined by linkage analysis and translocation breakpoints, the gene for NF1 is located on the long arm of chromosome 17, near the centromere (q11.2). It has been cloned and consists of 59 exons that are spread out over 350 kb of genomic DNA and gives rise to several alternatively spliced transcripts ( 7). The gene encodes a cytoplasmic protein, named neurofibromin, which contains a large amino acid segment that is homologous to the functional domain of the p21ras-GTPase activating protein. This protein inactivates the tumor gene p21ras by stimulating its GTPase activity and converting the active form of p21ras into its inactive form. Inasmuch as the active form of p21ras is a specific growth regulator for astrocytes, the NF1 gene functions as a tumor-suppressor gene (8,9,9a). This is confirmed by the observation that loss of NF1 gene expression occurs in at least some neurofibroma, in neurosarcoma, and in leukemic cells derived from NF1 subjects (8,10,11). Neurofibromin also has been shown to be associated with cytoplasmic microtubules in the brain and is believed to be involved in signaling within the central nervous system (CNS). The NF1 gene is large and is intrinsically hypermutable; more than 100 mutations have been described, and only rarely has the same mutation been identified in unrelated patients. Mutations include large deletions seen in 7.5% to 17% of patients ( 12,12a), frame shifts, stop mutations, and point mutations. The majority (60% to 70%) of mutations result in the formation of truncated and nonfunctioning neurofibromin. Somatic mosaicism is fairly common; its exact frequency has not been ascertained (12). NF1 gene expression is complex and is modulated posttranscriptionally by numerous alternative splicings and RNA editing ( 13). Some of the alternative transcripts lack tumor suppressor activity and are developmentally regulated. Their role in producing the clinical phenotype of NF1 is not understood (13,14). It, therefore, comes as no surprise that there is much variability in the expression of NF1, even within the same family. Correlation between the genetic mutation and the clinical expression is poor. However, a significant proportion of subjects with severe manifestations including dysmorphic features have large deletions in the NF1 gene (15). Pathology The most striking neuropathologic feature is the presence of tumors along the major peripheral nerves, with the ulnar and radial nerves being involved most frequently. Neurofibromas are the most common tumor type, but schwannomas also can be seen. Tumors that are prone to develop within the CNS include primarily optic gliomas; pilocystic astrocytomas of the third ventricle, cerebellum, and spinal cord; and high-grade astrocytomas ( 16). Additionally, neurofibromatosis has been associated with a number of other neoplastic processes with a greater than random frequency ( 17). These include leukemia, Wilms tumor, neuroblastoma, and pheochromocytoma. A syndrome of multiple endocrine neoplasia characterized by bilateral pheochromocytomas, medullary thyroid carcinoma, and multiple neuromas and café au lait lesions has been delineated ( 18). Although generally benign, both central and peripheral neurofibromas can undergo malignant degeneration. This is particularly likely to occur with the plexiform neurofibroma, for which the risk for malignant transformation to neurofibrosarcoma has been estimated at 5% ( 19). Clinical Manifestations NF1 is a progressive disease process that can affect almost every organ. When many peripheral lesions are present, few lesions tend to be within the CNS. The reverse also is true (20). The most common skin lesions are the café au lait spots. These are numerous light brown areas, usually located over the trunk, with smooth, well-defined borders and uniform pigmentation. They are seen in virtually every patient with NF1, and they result from an aggregation of neural crest-derived pigmented melanoblasts in the basal layer of the epidermis (4). They are present at birth and their number and size increase until puberty. According to Crowe and associates, at least six such lesions are necessary for a diagnosis of NF1 (21). Less frequent are diffuse freckling, freckling under the armpits, and large areas of faintly increased pigmentation (melanoderma). Although usually present before the onset of neurologic symptoms, these pigmentary abnormalities are not striking during infancy but intensify with age, particularly after puberty. Various types of cutaneous tumors can be found (Fig. 11.1). The most characteristic for NF1 is the pedunculated molluscum fibrosum and the subcutaneous neurofibromas. The latter consist of an overgrowth of Schwann cells admixed with tortuous nerve fibers and perineural fibroblasts. They are located singly or in groups along nerve trunks. Generally, cutaneous tumors tend to enlarge slowly throughout life. Plexiform neuromas can occur in all affected tissues and lead to hypertrophy of one or more extremity, exophthalmos, or defects of the skull and orbit. Multiple nodules within the iris (iris hamartomas) ( Fig. 11.2) were first described by Lisch (22). Lisch nodules are seen in almost all affected individuals aged 21 or more years, but only in one-half of children aged 5 to 6 years ( 23). Initially light colored, they become darker with time. FIG. 11.1. Neurofibromatosis. Posterior view demonstrating various types of cutaneous tumors. These include the pedunculated molluscum fibrosum and subcutaneous neurofibromas. Note the area of hyperpigmentation of the right elbow and a typical café au lait lesion. (Courtesy of Dr. V. M. Riccardi, Neurofibromatosis Institute, La Crescenta, CA.) FIG. 11.2. Lisch nodules of iris L). (Courtesy of Dr. Bronwyn Bateman, Department of Ophthalmology, University of Colorado School of Medicine, Denver.) Short stature is common. It was seen in 31.5% of patients in the series of Huson and Rosser ( 4). A large proportion of these children experiences growth hormone deficiency. The cause of this deficiency is not clear; in some instances it is probably the result of an intracranial tumor involving the hypothalamic region ( 23a). Various skeletal abnormalities have been described. Of these, low cervical or thoracic kyphoscoliosis is encountered most often. It was noted in 32% of children in the series of Holt, and its incidence increases with age ( 24). Less commonly, one observes scalloping of the posterior portion of the vertebral bodies. This scalloping is caused by a dural ectasia, the consequence of congenital weakness of the dura and the resulting pressure on the vertebral bodies. Anterior and lateral meningoceles, which are more common in adults, also result from the dural weakness. Bony rarefactions, the consequence of subperiosteal neurofibromas, can arise within the spine, the pelvis (particularly the iliac wings), or the skull. These rarefactions can induce pathologic fractures. Bony overgrowth, often with contiguous elephantiasis, is seen in approximately 10% of patients. Radiographic findings are reviewed by Holt ( 24) and Klatte and coworkers (25). Hypertension can develop owing to the presence of a pheochromocytoma, which is seen in 1% to 4% of subjects. It also can be the result of renal artery stenosis, the most common of a variety of arterial abnormalities seen in neurofibromatosis ( 26,27). The microscopic picture of these arterial abnormalities is one of an intense subintimal proliferation of the spindle cells, which are believed to be of Schwann cell origin. Neurologic manifestations can be grouped into five major categories ( 28,29). Cognitive Disabilities Although as many as 40% of children with neurofibromatosis have learning disabilities, only a small proportion are severely retarded ( 19,30). Thus, in the series of Ferner and colleagues only 8% of patients with NF1 had an IQ below 70 ( 31). All studies designed to investigate the cognitive deficits of NF1 subjects have shown a significant lowering in full-scale IQ when compared with unaffected siblings ( 31,32). As a rule, children tend to do better on verbal than on performance tasks and show deficits in visuospatial areas, attention, short-term memory, and reading ( 31,32). These deficits are believed to result from cortical heterotopias and other malformations of cerebral architecture such as glial nodules and other hamartomatous lesions ( 33), as well as from the presence of abnormal myelin. Malformations have been demonstrated by magnetic resonance imaging (MRI) as small focal areas of increased signal ( unidentified bright objects) on T2-weighted scans in at least 43% of patients with neurofibromatosis (34). Areas of increased signal are located with particular frequency in the globus pallidus, brainstem, and cerebellum ( 35). Generally, they are asymptomatic and do not progress; rather, they tend to diminish or disappear over the years. In the experience of DiMario and Ramsby, lesions in the basal ganglia and cerebellum decrease in size and number over time, whereas lesions in the brainstem tended to increase in both number and size ( 36). Studies present conflicting data as to whether the number of abnormalities seen on MRI correlates with the severity of cognitive deficits ( 37,38). When lesions are seen in the brainstem they should not be confused with a neoplasm (33). Macrocephaly is common, and 16% of children in Riccardi's series and 45% of children in the series of Huson and Rosser had a head circumference at or above the 98th percentile ( 4,19,30). We have not seen a patient with neurofibromatosis and microcephaly. Intracranial Tumors Intracranial tumors can arise at any time of life, the optic pathway being the most common and the earliest site of involvement ( 39). In the series of Holt, optic pathway gliomas were found in 23% of children with neurofibromatosis (24). This compares with an incidence of 15% in the series of Huson and Rosser ( 4) and 19% in the series of Listernick and colleagues ( 40). The tumor is benign and histologically corresponds to a pilocystic astrocytoma. It is more common in girls, with a female to male ratio of 2:1 (40). Approximately one-half of patients who harbor optic pathway tumors develop signs or symptoms. The principal initial symptoms include proptosis and precocious puberty. The latter is seen in approximately 40% of subjects and results from compression of the hypothalamus by the tumor. The presence of precocious puberty in a child with NF1, therefore, should always arouse the suspicion of an enlarging intracranial tumor. Decreased visual acuity is rarely a presenting complaint in children even though it can be demonstrated by examination. The natural history of these optic pathway tumors in subjects with NF1 is not known and their growth rate differs considerably from one patient to the next. In the series of Listernick and colleagues ( 40) no tumor growth was seen as determined by MRI over a mean interval of 2.4 years. Only a small proportion of intraorbital tumors progress, whereas tumors that involve the optic chiasm are more likely to progress. The consensus statement from the NF1 Optic Pathway Glioma Task Force has concluded that MRI screening of children with NF1 for optic pathway gliomas has only limited value, and even though asymptomatic tumors are often found these only rarely progress. Serial visual acuity examinations in symptomatic children are preferable and less costly. Radiotherapy has been shown to halt tumor progression, but there has been concern that it could transform the tumor to a higher grade glioma (41). Focal or generalized seizures can appear early in childhood and were seen in 7% of patients in the series of Huson and Rosser ( 4). Some of these patients had an electroencephalographic picture consistent with hypsarrhythmia. Because a significant proportion of patients with seizures and neurofibromatosis are ultimately found to have intracranial tumors, a child with cutaneous neurofibromatosis and seizures should be suspected of harboring a tumor and should receive imaging studies. Tumors of the Peripheral Nerves Tumors of the peripheral nerves can arise at any age and can involve any of the major nerves. Even though these tumors are occasionally painful, surgical removal must be weighed carefully against the possibility of the procedure producing considerable neurologic deficit. Malignant degeneration of neurofibromas occurs in less than 3% of children, but appears more frequently in adults ( 19). Tumors also can arise within the autonomic nerve supply of various viscera. According to Kissel and Schmitt, the stomach, tongue, mediastinum, large intestines, and adrenal medulla are the most common sites (42). Intraspinal Tumors Intraspinal tumors are generally slower to develop than intracranial tumors and asymptomatic spinal cord tumors are commonly detected on routine neuroimaging studies. The youngest patient with a symptomatic intraspinal tumor in Canale's series was 20 years of age ( 28). Approximately one-half of intraspinal tumors are multiple, and occasionally, they are accompanied by malformations such as syringomyelia. Familial spinal neurofibromatosis is a variant of NF1. The condition is marked by the development of multiple spinal cord tumors during adult life ( 42,43 and 44). Cerebrovascular Accidents Cerebrovascular accidents are common and can be responsible for the abrupt evolution of neurologic signs. They result from cerebrovascular occlusive disease and most commonly affect the supraclinoid portion of the internal carotid artery or one of its major branches ( 45,46). More than one-half of the patients with occlusive disease of the internal carotid have the arteriographic picture of moyamoya disease ( 45,46). The incidence of some of the neurologic manifestations encountered in NF1 and NF2 is presented in Table 11.1 (28). TABLE 11.1. Neurologic manifestations in 92 patients with neurofibromatosis (NF1 and NF2) Several conditions are related to NF1. Watson syndrome, characterized by dominantly transmitted pulmonary valve stenosis, café au lait spots, and low to normal intelligence, is believed to be allelic with NF1 ( 47). The concurrence of Noonan syndrome with NF1 may represent either a contiguous gene syndrome or the coincidental segregation of two autosomal dominant conditions ( Chapter 3). Diagnosis Despite the advances in understanding the molecular biology for NF1 and NF2, the diagnosis for both conditions is still largely based on clinical criteria. The diagnostic criteria for NF1 are two or more of the following: Six or more café au lait macules whose greatest diameter is more than 5 mm in prepubertal patients and more than 15 mm in postpubertal patients Two or more neurofibromas of any type, or one or more plexiform neurofibroma Freckling in the axillary or inguinal region Optic glioma (tumor of the optic pathway) Two or more Lisch nodules (iris hamartomas) A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex A first-degree relative with NF1 according to the previously mentioned criteria ( 48,49 and 50) DNA testing for the diagnosis of NF1 is limited, because present techniques detect only approximately 70% of mutations ( 4). Although a solitary café au lait spot can occur in the normal population, the incidence of more than four such lesions in nonaffected persons is low, and, in the absence of other symptoms of neurofibromatosis, the lesions can indicate a partial penetrance of the disease ( 51). Conversely, some 75% of individuals with proven NF1 have six or more caféau lait spots 1 cm or more at the largest diameter (21). Both parents should be examined with particular attention to the presence of café au lait spots, subcutaneous neurofibromas, and Lisch nodules. Detection of Lisch nodules often requires slit-lamp examination by an ophthalmologist. If one parent has the stigmata of NF1, the condition in the offspring is not a new mutation, and a 50% chance exists for it to occur in each subsequent sibling. The risk for the patient's own potential offspring is the same. If neither parent has any abnormalities, a new mutation is presumed, and the recurrence risk for NF1 is no greater than in the general population. Prenatal diagnosis of the condition can be made by linkage analysis, if two or more family members are affected (50). Treatment and Prognosis Therapy is symptomatic. Most pediatric patients with NF1 should be seen in a multispecialist clinic at intervals of at least 6 months to 1 year to detect and manage the various potential complications. The necessity or value of routine cranial MRI scans is a matter of debate, because it is becoming apparent that the detection of asymptomatic lesions does not alter clinical management (50). Surgical removal of centrally located neoplasms is often life saving. When tumors are confined to peripheral nerves, the long-term prognosis is generally good. The prognosis for intracranial tumors depends on their location and whether they are single or multiple. In a follow-up study of patients with NF1 first reported in 1951, Sorensen and coworkers found that survival was limited by an incidence of neoplasms that was four times greater than seen in the normal population. Thus, 84% of patients developed a glioma, and second tumors were seen five to eight times more frequently than expected. Malignancies were encountered in one-third of the cohort, with female subjects having a higher incidence than male subjects. Second neoplasms were seen in 83% of patients with optic gliomas and in 43% of patients with other types of gliomas ( 52). Neurofibromatosis 2 NF2 is genetically and clinically distinct from NF1. It is far less common, with an estimated incidence of 1 in 33,000 to 40,000, and it is characterized by the development of CNS tumors, notably bilateral vestibular schwannomas (49). The gene for NF2 has been mapped to the long arm of chromosome 22 (22q11) and has been cloned. Its gene product, merlin (schwannomin), shares significant homology with several actin-associated proteins ( 49a). Merlin is localized to the cell membrane and is believed to act as a membrane-cytoskeletal linker. It serves as a tumor suppressor by playing a role in the regulation of cell-cell adhesion, and in the reorganization of the actin cytoskeleton in response to growth factors, confluency, and changes in the shape of the cell ( 53,54). Merlin is absent from almost all schwannomas and from many meningiomas and ependymomas isolated from subjects with NF2. A large number of gene mutations have been documented. Some 90% of patients have gross truncations of merlin as a result of nonsense or frame-shift mutations ( 55). These patients tend to be younger at onset of symptoms and at diagnosis, and tend to harbor a large number of tumors (56). Clinical Manifestations In contrast to NF1, clinical manifestations and age of onset are similar within a given family, but differ considerably between families ( 57). The clinical manifestations of NF2 are highlighted by the presence of bilateral vestibular schwannomas (acoustic neuromas), which become manifest in more than 95% of genetically affected subjects (58). Generally, these tumors become symptomatic at puberty or thereafter. In addition, schwannomas occur in the other cranial nerves and the spinal and cutaneous nerves. Other tumors of the CNS seen in this condition include cranial and spinal meningiomas and multiple tumors of glial and meningeal origin. These tumors are readily detectable by imaging studies, with the acoustic neuromas appearing as a mass in the cerebellopontine angles or enlargement of the gasserian ganglia (34,59). As a rule, the mean age of onset of symptoms is in the second decade of life. In the series of Mautner and colleagues it was 17 years, with the age ranging from 2 to 36 years (59). In the same series, 44% of patients presented with deafness. Café au lait lesions were present in only 43% and in this series as in others they rarely number more than six (60,61). Cataracts (posterior subcapsular or cortical) were seen in 81%, and seizures were presenting complaints in 8%. Peripheral nerve tumors were seen in 68%. These are predominantly schwannomas, but also can be neurofibromas ( 60). These appear as discrete, well-circumscribed slightly raised lesions with a roughened, slightly pigmented surface. Other skin lesions such as nodular tumors or neurofibromas also are less common than in NF1. According to Riccardi, acoustic neuromas and optic glioma never coexist in a patient ( 19). Diagnosis As is the case for NF1, the diagnosis of NF2 rests on clinical grounds. The criteria for NF2 are one or more of the following conditions: Bilateral eighth nerve masses (vestibular schwannomas) seen with imaging techniques A parent, sibling, or child with NF2 and either unilateral eighth nerve mass or any two of the following conditions: neurofibroma, meningioma, glioma, schwannoma, or juvenile posterior subcapsular lenticular opacity ( 48,60,62) Patients with unilateral vestibular schwannomas and cataracts, or meningioma, glioma, or schwannoma are suspect for NF2, as are patients with multiple meningiomas plus unilateral vestibular schwannoma, cataracts, or glioma (60). In 10% of cases of NF2 there is an identifiable mutation in merlin; for the remainder of patients, prenatal diagnosis requires a linkage study using DNA derived from at least two affected family members, if these are available. Tuberous Sclerosis Although the earliest report of a patient with TS is said to have been made by von Recklinghausen in 1863 ( 63), its first complete, albeit mainly pathologic, description is attributed to Bourneville, who, in 1880, was the first to call it TS ( 64). This is a protean disorder, chiefly manifested by mental deficiency, epilepsy, and skin lesions. It occurs with a frequency of 1 in 6,000 to 15,400 and is transmitted as an autosomal dominant gene ( 65,66). Approximately one-third of cases are familial, and the rest are new mutations. TS is genetically heterogeneous, with loci on chromosome 9q34.3 ( TSC1), and 16p13.3 (TSC2). Each locus accounts for approximately 50% of familial cases (67). The phenotypic expression of the two genetic defects appears to be similar if not identical. TSC1 codes for hamartin, a 130-kd protein with no significant homology to any other known vertebrate protein (68). TSC2 codes for tuberin, a 200-kd protein, which functions as a tumor-suppressor gene ( 69). It acts as a GTPase activator for rap1, which is an effective proliferation signal, expressed in several tissues, notably astrocytes. Rap1 also is involved in morphogenesis and cell migration ( 69a). Tuberin is most abundant in cerebral gray matter and increases during prenatal and postnatal development ( 70). The protein also may be involved in neuronal differentiation (71). Hamartin and tuberin associate physically in vivo, and inactivation of either is believed to prevent the formation of a functional protein complex (72). Mutations in the TSC2 genes are more readily detected in sporadic than in familial cases ( 73). Penetrance is variable. No family with two or more affected offspring has been encountered in which one parent did not have adenoma sebaceum or some other skin lesion characteristic for TS ( 74). Conversely, the risk of having more than one affected child is low when both parents are clinically unaffected because under such circumstances the condition is probably a new mutation. Pathology Abnormalities can be found in the brain, eyes, skin, kidneys, bones, heart, and lungs. In the brain, three types of abnormalities occur: cortical tubers, subependymal nodules, and disorders of myelination. The most characteristic gross abnormality is the presence of tubers. These are numerous hard areas of gliotic tissue of varying size, after which this condition is named. Tubers can be located in the convolutions of any part of the cerebral hemispheres ( Fig. 11.3). Less commonly they are in the cerebellum, brainstem, or spinal cord. On histologic examination they are sclerotic areas that consist of an overgrowth of atypical giant astrocytes, and groups of large, bizarre, and frequently vacuolated “monster cells.” Blood vessels in sclerotic regions show hyaline degeneration of their walls. In approximately one-half of subjects, calcium is deposited within the gliotic areas to an extent as to be visible on plain radiography of the skull or on computed tomographic (CT) scanning ( Fig. 11.4). Subependymal nodules are found in the ventricular walls, particularly in the region of the foramen of Monro. They are multiple small, tumor-like nodules that project into the ventricles and that because of their appearance on pneumoencephalography were described as “candle drippings.” Calcification of these nodules is common and increases with age. Subependymal giant cell astrocytomas arise from subependymal nodules, particularly in the area surrounding the foramen of Monro, and transitions between gliosis and astrocytomas are common. Their incidence in TS is approximately 10% to 15% ( 75). Although only rarely malignant, they often obstruct the foramen of Monro. It is of note that approximately one-half of high-grade and low-grade sporadic adult astrocytomas show reduced or absent expression of tuberin (75a). In the remainder, the majority have an increased expression of rap1. FIG. 11.3. Tuberous sclerosis. A large intraventricular tuber produces increased intracranial pressure, flattening of the gyri, and herniation of the right temporal uncus (U). (Courtesy of Dr. P. Cancilla, Department of Pathology, University of California, Los Angeles, UCLA School of Medicine.) FIG. 11.4. Noncontrast computed tomographic scan of tuberous sclerosis, taken at several levels, shows typical calcified subependymal tubers at the margins of the lateral ventricles and projecting slightly into the ventricles. (Courtesy of Dr. Hervey D. Segall, Children's Hospital of Los Angeles.) Myelination usually is diminished in the gliotic areas within and surrounding the cortical tubers. In addition, islets occur consisting of heterotopic cells within white matter. These are distributed in a linear pattern that follows the normal migratory path of primitive neurons between the germinal layer of the ventricles and the cortical surface. Tumors also can arise from various viscera. In the heart, the characteristic lesion is the rhabdomyoma. The incidence of these tumors in children with TS can be as high as 50%. Characteristically, they are multiple and well circumscribed. Rhabdomyomas cause as many as one-fourth of infants to die from circulatory failure during the first few days of life, well before developing other stigmata of TS. Between 50% and 80% of patients develop multiple renal tumors, which are usually benign and of mixed embryonal type. Lungs are rarely involved, but when lesions are present in the lungs they are usually cystic or fibrous. Other organs can be the seat of fibrocellular hamartomas (1). The pathologic features of the disease are extensively reviewed by Bender and Yunis ( 76). Clinical Manifestations Manifestations of TS vary considerably with respect to age of onset, severity, and rate of progression. The four main types of manifestations are mental retardation, seizures, cutaneous lesions, and tumors in various organs including the brain. The frequency of the major signs and symptoms is given in Table 11.2 (77). TABLE 11.2. Clinical picture in 71 patients with tuberous sclerosis The degree of mental retardation varies widely, and for unknown reasons, a significant proportion of youngsters develops autistic features. Approximately one-third of patients diagnosed as having TS on the basis of other clinical manifestations maintain a normal intelligence. In others, language and perceptual development is slowed. Of retarded patients studied by Borberg, 15% developed normally for the first few years of life, showing the first signs of intellectual deterioration between 8 and 14 years of age (78). This deterioration can be the consequence of either frequent, uncontrolled seizures or the development of increased intracranial pressure caused by an obstruction at the foramen of Monro. In some series the number of tubers is greater in subjects with mental retardation than in those with normal intelligence, whereas in others there is no consistent relationship between intelligence and the number of tubers, and mental retardation reflects the early onset of seizures (75,79). Seizures, the most common presenting complaint in all patients with TS, occur at some time in all patients who are retarded. Infantile spasms are the most common seizures during infancy (80). Between one-fourth and one-half of children presenting with this type of seizure ultimately develop TS ( 81). Later, generalized convulsions or focal seizures can occur. Seizures can appear as early as the first week of life. The earlier the onset of seizures, the more likely the infant is to be mentally retarded (Table 11.2). Of 90 children whose seizures began before 1 year of age, only 8% were deemed to have average intelligence ( 82). Gomez and colleagues have postulated the presence of an epileptogenic factor, independent of cerebral TS, that facilitates the early onset of seizures, and, in turn, impairs normal CNS development (83). The severity of the seizures is unpredictable ( 84). As is discussed in Chapter 13, vigabatrin (150 mg/kg per day) is extremely effective in the management of infantile spasms caused by TS and is now considered to be the treatment of choice ( 85). Autism or pervasive developmental disorder is a prominent feature of TS. In a series of TS patients from the University of California, Los Angeles, 28.5% satisfied the clinical features for autism, and a further 14.2% met the criteria for pervasive developmental disorder ( 86). In other series of patients with TS the incidence of autistic disorders was even higher (87). Bolton and Griffiths have commented on the association of autism with tubers within the temporal lobes ( 88). This challenging observation needs to be confirmed. Adenoma sebaceum (angiofibroma) is the characteristic cutaneous lesion of TS ( Fig. 11.5). These lesions consist of a red, papular rash over the nose, chin, cheeks, and malar region, appearing between ages 1 and 5 years. In the experience of Pampiglione and Moynahan, 12% of affected children developed this skin lesion by 1 year of age, and 40% by 3 years of age (89). Depigmented nevi, resembling vitiligo, in the form of oval areas with irregular margins ( ash leaf) over the trunk and extremities are equally common. Generally, they appear earlier than the adenoma sebaceum. They can be noted at birth and are seen before 2 years of age in more than one-half of the subjects (89,90). They are more readily visualized when the skin is illuminated with ultraviolet light (Wood lamp). Depigmented nevi differ from vitiligo in that in vitiligo the melanocytes are absent, whereas in depigmented macules the melanocytes are normal, but the melanosomes are reduced and contain less melanin. Hypopigmented macules are seen in 0.8% of apparently healthy newborns ( 91). FIG. 11.5. Tuberous sclerosis. Characteristic fibrous plaque of the forehead and facial angiofibroma in a boy with an early stage of the condition. (From Gomez MR, ed. Neurocutaneous diseases. A practical approach. Boston: Butterworths, 1987. With permission.) Of the other cutaneous abnormalities, flattened fibromas are the most common. They appear in a variety of areas, including the trunk, gingivae, and periungual regions. In some infants, fibromas are found along the hairline or eyebrows. Another striking, but less common, lesion is the shagreen patch. This is an uneven thickening of skin, grayish green or light brown, raised above the surrounding surface, usually in the posterior lumbosacral region. Café au lait spots are seen in 7% to 16% of subjects. Their incidence is not much greater than in the general population and their presence in isolation should not prompt the diagnosis of neurofibromatosis. A significant percentage of subjects have patches of gray or white hair. Their presence can precede that of the depigmented nevi and thus can be [...]... NMDA antagonists in ischemic stroke Neurology 1997;49[Suppl 4]: S66S69 72a.Lees KR Does neuroprotection improve stroke outcome? Lancet 19 98; 351:144714 48 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 Sutor AH, et al Heparin therapy in pediatric patients Semin Thromb Hemost 1997;23:303319 Massicotte P, et al Low-molecular-weight heparin in pediatric patients... 137 1 38 139 140 141 142 143 144 145 146 147 1 48 149 150 151 152 153 154 155 156 157 1 58 159 160 161 162 163 164 165 166 167 1 68 169 170 171 172 173 174 175 176 177 1 78 179 180 181 182 183 184 185 186 187 188 Maria BL, Neufeld JA, Rosainz LC, et al High prevalence of bihemispheric structural and functional defects in Sturge-Weber syndrome J Child Neurol 19 98; 13:595605 Lindau A Studien ỹber Kleinhirncysten:... 1 988 ;319:2 782 83 Mautner VF, et al The neuroimaging and clinical spectrum of neurofibromatosis 2 Neurosurgery 1996; 38: 880 885 Mautner VF, et al Skin abnormalities in neurofibromatosis 2 Arch Dermatol 1997;133:15391543 Evans DG, et al A clinical study of type 2 neurofibromatosis QJM 1992 ;84 :6036 18 Martuza RL, Eldridge R Neurofibromatosis 2 (bilateral acoustic neurofibromatosis) N Engl J Med 1 988 ; 3 18: 684 688 ... arteries associated with glycogenosis type 2 (Pompe's disease) Neurosurgery 1 987 ;21:7 487 49 179 Thompson JR, Harwood-Nash DC, Fitz CR Cerebral aneurysms in children Am J Roentgenol 1973;1 18: 163175  180 181 182 183 184 185 186 Patel AN, Richardson AE Ruptured intracranial aneurysm in the first two decades of life A study of 58 patients J Neurosurg 1971;35:571576 Chapman AB, et al Intracranial aneurysms... Intracranial aneurysms in the pediatric age-group Childs Brain 1 982 ;9:3 583 61 167 Sedzimir CB, Robinson J Intracranial hemorrhage in children and adolescents J Neurosurg 1973; 38: 269 281 1 68 Heiskanen O, Vilkki J Intracranial arterial aneurysms in children and adolescents Acta Neurochir 1 981 ;59: 5563 169 Read D, Esiri MM Fusiform basilar artery aneurysm in a child Neurology 1979;29:10451049 170 Zimmerman... 1 988 ;10:4151 16 Riela AR, Roach ES Etiology of stroke in children J Child Neurol 1993 ;8: 201220 17 Young W The post-injury responses in trauma and ischemia: secondary injury or protective mechanisms? CNS Trauma 1 987 ;4:2751 18 Macdonald RL, Stoodley M Pathophysiology of cerebral ischemia Neurol Med Chir (Tokyo) 19 98; 38: 111 19 Kristin T, Siesjử BK Calcium in ischemic cell death Stroke 19 98; 29:7057 18 20... Headaches and subarachnoid haemorrhage Lancet 1 988 ;1 :80 Jenkins A, et al Magnetic resonance imaging of acute subarachnoid hemorrhage J Neurosurg 1 988 ; 68: 731763 Weisberg LA Computed tomography in aneurysmal subarachnoid hemorrhage Neurology 1979;29: 80 280 8 Wiebers DO, et al The significance of unruptured intracranial saccular aneurysms J Neurosurg 1 987 ;66: 2329 186 a Caplan LR Should intracranial aneurysms... skull base CT Radiology 1992; 182 :477 481 Chapter 13 Paroxysmal Disorders Child Neurology Chapter 13 Paroxysmal Disorders John H Menkes and RRaman Sankar Departments of Neurology and Pediatrics, University of California, Los Angeles, UCLA School of Medicine, and Department of Pediatric Neurology, Cedars-Sinai Medical Center, Los Angeles, California 900 48; and RDepartments of Neurology and Pediatrics, University... Disorders Child Neurology Chapter 12 Cerebrovascular Disorders John H Menkes and RHarvey B Sarnat Departments of Neurology and Pediatrics, University of California, Los Angeles, UCLA School of Medicine, and Department of Pediatric Neurology, Cedars-Sinai Medical Center, Los Angeles, California 900 48; and RDepartments of Pediatric Neurology and Neuropathology, University of Washington School of Medicine, Children's... Kisco, NY: Futura, 1 988 Sutor AH, Uhl M Diagnosis of thromboembolic disease during infancy and childhood Semin Thromb Hemostasis 1997;23:237246 Bogousslavsky J, et al Migraine stroke Neurology 1 988 ; 38: 223227 Andrew M Indications and drugs for anticoagulation therapy in children Thromb Res 1996 ;81 [Suppl 2]: S61S73 Zenz W, et al Intracerebral hemorrhage during fibrinolytic therapy in children: a review . 1 988 ;23:575–579. 86 . Radcliffe J, et al. Three- and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain-radiotherapy. Ann Neurol 1992;32:551–554. 87 recurrent cerebellar astrocytoma. Childs Brain 1 983 ;10:1 68 176. 143. Civitello LA, et al. Leptomeningeal dissemination of low-grade gliomas in childhood. Neurology 1 988 ; 38: 562–566. 144. Rubinstein. 1996 ;85 :73 81 . 285 . Fisher PG, et al. Outcomes and failure patterns in childhood craniopharyngiomas. Childs Nerv Syst 19 98; 14:5 58 563. 286 . Richmond IL, Wilson CB. Parasellar tumors in children.