Clinical and cranial magnetic resonance aspects in patients with neurofibromatosis type 1 Original Article

Abstract

In this study we aimed to evaluate clinical the findings and cranial MRI findings especially in neurological aspect and to search for the relationship between the lesions on MRI and behavior cognitive disorders in Neurofibromatosis type 1 NF 1 patients Thirty one patients with NF 1 between the ages of 3 19 years mean 9 7±4 6 who had no other cranial MRI findings except optic gliyoma and NF 1 hyper intense lesions NHL on T2 weighted images were included in the study Denver II test was performed to all patients under 6 years old and WISC R and or Porteus test to the patients over 6 years The locations and extensions of the NHLs in total 46 MRI were noted and the relationship between these findings and behavior cognitive disorders were analyzed Benign seizure history in four recurrent headache attacks in six patients and behavior cognitive disorder in 50 of 22 patients over 6 years old were determined In evaluated total 46 MRIs optic gliyoma was in a ratio of 16 NHLs were sited most frequently in basal ganglia brain stem and cerebellum No relation was found between behavior cognitive disorders and the location number of locations and extension of NHLs In conclusion neuropsychological evaluation should be performed since behavior cognitive disorders might be seen commonly in NF 1 patients These disorders could be influenced by other parameters apart from NHLs on T2 weighted MRIs Key words: cognitive function disorders cranial magnetic resonance imaging nörofibromatosis type1

Keywords

• -

Nörofibromatozis tip 1 hastalarında klinik ve kraniyal manyetik rezonans görüntüleme özellikleri Orijinal Araştırma

Abstract

Bu çalışma nörofibromatozis tip 1 NF 1 hastalarında klinik ve kraniyal MRG bulgularını özellikle nörolojik yönden değerlendirmek MRG lezyonlarının davranış bilişsel işlev bozuklukları ile ilişkisini araştırmak amacıyla planladı Çalışmaya NF 1 tanısıyla izlenen ve kraniyal T2 ağırlıklı MRG’sinde NF 1’e özgü hiperintens lezyonlar NHL ve optik gliyom dışında başka bulgusu olmayan 3 19 yaş ort 9 7±4 6 arasında toplam 31 hasta alındı Altı yaş altında Denver II 6 yaş üstünde porteus ve veya WISC R testleri uygulandı Toplam 46 kraniyal MRG’deki NHL’lerin yerleşimleri yaygınlıkları incelendi ve bunların davranış bilişsel işlev bozukluklarıyla ilişkisi araştırıldı Dört hastada selim seyirli nöbet öyküsü altı hastada yineleyen başağrısı altı yaşın üstündeki 22 hastanın 50’sinde davranış bilişsel işlev bozukluğu tespit edildi Toplam 46 MRG değerlendirildiğinde optik gliyom 16 oranında gözlendi NHL’ler ise sıklıkla bazal gangliya beyin sapı beyincikde gözlenmekteydi NHL’lerin yerleşimlerinin yerleşim sayısının ve yaygınlığının davranış bilişsel işlev bozuklukları ile ilişkisi bulunmadı Sonuç olarak NF 1 hastalarında davranış bilişsel işlev bozukluğu sıklıkla görülebileceğinden nöropsikolojik değerlendirme mutlaka yapılmalıdır Bu bozuklukların T2 ağırlıklı MRG’lerde gözlenen NHL’ler dışında başka değişkenlerden de etkilendiği düşünülmektedir Anahtar Kelimeler: kognitif fonksiyon bozuklukları kraniyal manyetik rezonans görünteleme nörofibromatozis tip 1

Keywords

• kognitif fonksiyon bozuklukları, kraniyal manyetik rezonans görünteleme, nörofibromatozis tip 1

References

1. Balestri P, Calistri L, Vivarelli R, et al. Central nervous system imaging in reevaluation of patients with neurofibromatosis type 1. Childs Nerv Syst 1993; 9: 448- 51.
2. DiMario FJ, Ramsby G. Magnetic resonance imaging lesion analysis in neurofibromatosis type 1. Arch Neurol 1998; 55: 500- 5.
3. Itoh T, Magnaldi S, White RM, et al. Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities. Am J Neuroradiol 1994; 15: 1513- 9.
4. Kraut MA, Gerring JP, Cooper KL, et al. Longitudinal evolution of unidentified bright objects in children with neurofibromatosis- 1. Am J Med Genet A. 2004; 129: 113- 9.
5. Ferner RE, Chaudhuri R, Bingham J, et al. MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment. J Neurol Neurosurg Psychiatry 1993; 56: 492- 5.
6. Joy P, Roberts C, North K, et al. Neuropsychological function and MRI abnormalities in neurofibromatosis type 1. Dev Med Child Neurol 1995; 37: 906- 14.
7. North KK, Riccardi V, Samango-Sprouse C, et al. Cognitive function and academic performance in neurofibromatosis 1: consensus statement from the NF-1 cognitive disorders task force neurology 1997; 48: 1121- 7.
8. Moore BD, Slopis JM, Schomer D, et al. Neuropsychological significance of areas of high signal intensity on brain MRIs of children with neurofibromatosis. Neurology 1996; 46: 1660- 8.

9. Denckla MB, Hofman K, Mazzocco MM, et al. Relationship between T2-weighted hyperintensities (unidentified bright objects) and lower IQs in children with neurofibromatosis- 1. Am J Med Genet 1996; 67: 98- 102.
10. Ozonoff S. Cognitive impairment in neurofibromatosis type 1. Am J Genet 1999; 89: 45- 52.
11. Goh WH, Khong PL, Leung CS, et al. T2-weighted hyperintensities (unidentified bright objects) in children with neurofibromatosis 1: their impact on cognitive function. J Child Neurol. 2004; 19: 853- 8.
12. Durmazlar N, Ozturk C, Ural B, et al. Turkish children’s performance on Denver II: effect of sex and mother’s education. Dev Med Child Neurol 1998; 40: 411- 6.
13. D'Angiulli A, Siegel LS. Cognitive functioning as measured by the WISC-R: do children with learning disabilities have distinctive patterns of performance? J Learn Disabil. 2003; 36: 48- 58.
14. Brett EM. Neuroctaneous syndromes In: Brett EM (ed). Pediatric Neurology. London: Churchill Livingstone, 1991: 571- 91.
15. Virdis R, Street ME, Bandello MA, et al. Growth and pubertal disorders in neurofibromatosis type 1. J Pediatr Endocrinol Metab 2003; 16 Suppl 2: 289- 92.
16. Rafia S, Garcia-Pena JJ, Lopez-Pison J, et al. Growth charts for the Spanish population with neurofibromatosis type 1. Rev Neurol 2004; 38: 1009- 12.
17. Roach ES. Neurocutaneous syndromes. Pediatr Clin North Am 1992; 39: 591-620.
18. Santos CC, Kandt RS. Recent advances in neurocutaneous syndromes Curr Opin Pediatr 1990; 2: 1075- 82.
19. Crawford AH, Schorry EK. Neurofibromatosis in children: the role of the orthopaedist. J Am Acad Orthop Surg 1999; 7: 217- 30.
20. Berg OB. Neurocutaneous syndromes: Phakomatoses and allied conditions. In: Swaiman KF (ed). Pediatric Neurology. USA: Mosby, 1994: 1045- 68.
21. Lewis RA, Gerson LP, Axelson KA, et al. Von Recklinghausen neurofibromatosis. II: Incidence of optic gliyoma. Ophthalmology 1984; 91: 929- 36.
22. Kornreich L, Blaser S, Schwarz M, et al. Optic pathway gliyoma: correlation of imaging findings with the presence of neurofibromatosis. R Am J Neuroradiol. 2001; 22: 1963- 9.
23. Hofman KJ, Harris EL, Bryan RN, et al. Neurofibromaosis type-1: the cognitive phenotype. J Pediatr 1994; 124: 1- 8.
24. Kulkantrakorn K, Geller TJ. Seizures in neurofibromatosis 1. Pediatr Neurol 1998; 19: 347- 50.
25. Vivarelli R, Grosso S, Calabrese F, et al. Epilepsy in neurofibromatosis 1. Child Neurol 2003; 18: 338- 42.
26. Clementi M, Battistella PA, Rizzi L, et al. Headache in patients with neurofibromatosis type 1. Headache 1996; 36: 10.
27. DiMario FJ Jr, Langshur S. Headaches in patients with neurofibromatosis-1. J Child Neurol 2000; 15: 235- 8.
28. DeBella K, Poskitt K, Szudek J, et al. Use of "unidentified bright objects" on MRI for diagnosis of neurofibromatosis 1 in children. Neurology 2000; 54: 1646- 51.
29. Aoki SA, Barkovich AJ, Nishimura K. Neurofibromatosis types 1 and 2: cranial MR findings. Radiology 1989; 172: 527- 34
30. Duffner PK, Cohen ME, Seidel FG, et al. The significance of MRI abnormalities in children with neurofibromatosis. Neurology 1989; 39: 373- 8.
31. Bognanno JR, Edwards MK, Lee TA, et al. Cranial MR imaging in neurofibromatosis. Am J Radiol 1988; 151: 381- 8.
32. DiPaola DP, Zimmerman RA, Rorke LB, et al. Neurofibramatosis type 1: pathologic substrate of high-signal-intensity foci of the brain. Radiology 1995; 195: 721- 4.
33. Committee on Genetics Health supervision for children with neurofibromatosis. Pediatrics 1995; 96: 368- 72.
34. Bonawitz C, Castillo Mauricio, Chin CT, et al. Usefulness of contrast material in MR of patients with neurofibromatosis type 1. Am J Neuroradiol Mar;1998 19: 541- 6.
35. Mirowitz SA, Sartor K, Grado M. High-intensity basal ganglia lesions on T1-weighted MR images in neurofibromatosis. Am J Neuroradiol 1989; 10: 1159- 63.
36. Feldmann R, Denecke J, Grenzebach M, et al. Neurofibromatosis type 1: motor and cognitive function and T2-weighted MRI hyperintensities. Neurology. 2003; 61:1 725- 8.
37. Sağlık Bakanlığı İstanbul Göztepe Eğitim ve Araştırma Hastanesi, Çocuk Sağlığı ve Hastalıkları Kliniği, İstanbul
38. Sonomed Tıbbi Görünteleme Merkezi, İstanbul 1.
39. National Institutes of Health Consensus Development Conference.
40. Arch Neurol 1988; 45: 577- 8. 2.
41. Gutmann DH. Recent insights into neurofibromatosis type
42. : clear genetic progress. Arch Neurol 1998; 55: 778- 80. 3.
43. Özmen M. Nörokütan hastalıklar. İçinde: Neyzi O, Ertuğrul
44. T (eds). Pediatri İstanbul: Nobel, 2002: 1368- 72. 4.
45. Steen GR, Taylor JS, Langston JW, et al. Prospective evaluation
46. of the brain in asymptomatic children with neurofibromatosis
47. type 1: relationship of macrocephaly to T1 relaxation changes
48. and structural brain abnormalities. Am J Neuroradiol 2001; 22: 810- 7. 5.
49. Van Es S, North KN, McHugh K, et al. MRI findings in
50. children with neurofibromatosis type 1: a prospective study.
51. Pediatr Radiol 1996; 26: 478- 87. 6.
52. Griffiths PD, Blaser S, Mukonoweshuro W, et al. Neurofibromatosis
53. bright objects in children with neurofibromatosis type 1: a proliferative potential ? Pediatrics 1999; 104: 49. 7. Goldstein SM, Curless RG, Donovan Post MJ, et al. A new sign of neurofibromatosis on magnetic resonance imaging of children. Arch Neurol 1989; 46: 1222- 4. 8. Aoki SA, Barkovich AJ, Nishimura K. Neurofibromatosis types 1 and 2: cranial MR findings. Radiology 1989; 172: 527- 34. 9. North K, Joy P, Yuille D, et al. Spesific learning disability in children with neurofibromatosis type 1: significance of MRI abnormalities. Neurology 1994; 44: 878- 83.
54. Balestri P, Calistri L, Vivarelli R, et al. Central nervous system imaging in reevaluation of patients with neurofibromatosis type 1. Childs Nerv Syst 1993; 9: 448- 51.
55. DiMario FJ, Ramsby G. Magnetic resonance imaging lesion analysis in neurofibromatosis type 1. Arch Neurol 1998; 55: 500- 5.
56. Itoh T, Magnaldi S, White RM, et al. Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities. Am J Neuroradiol 1994; 15: 1513- 9.
57. Kraut MA, Gerring JP, Cooper KL, et al. Longitudinal evolution of unidentified bright objects in children with neurofibromatosis- 1. Am J Med Genet A. 2004; 129: 113- 9.
58. Ferner RE, Chaudhuri R, Bingham J, et al. MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment. J Neurol Neurosurg Psychiatry 1993; 56: 492- 5.
59. Joy P, Roberts C, North K, et al. Neuropsychological function and MRI abnormalities in neurofibromatosis type 1. Dev Med Child Neurol 1995; 37: 906- 14.
60. North KK, Riccardi V, Samango-Sprouse C, et al. Cognitive function and academic performance in neurofibromatosis 1: consensus statement from the NF-1 cognitive disorders task force neurology 1997; 48: 1121- 7.
61. Moore BD, Slopis JM, Schomer D, et al. Neuropsychological significance of areas of high signal intensity on brain MRIs of children with neurofibromatosis. Neurology 1996; 46: 1660- 8.
62. Denckla MB, Hofman K, Mazzocco MM, et al. Relationship between T2-weighted hyperintensities (unidentified bright objects) and lower IQs in children with neurofibromatosis- 1. Am J Med Genet 1996; 67: 98- 102.
63. Ozonoff S. Cognitive impairment in neurofibromatosis type 1. Am J Genet 1999; 89: 45- 52.
64. Goh WH, Khong PL, Leung CS, et al. T2-weighted hyperintensities (unidentified bright objects) in children with neurofibromatosis 1: their impact on cognitive function. J Child Neurol. 2004; 19: 853- 8.
65. Durmazlar N, Ozturk C, Ural B, et al. Turkish children’s performance on Denver II: effect of sex and mother’s education. Dev Med Child Neurol 1998; 40: 411- 6.
66. D'Angiulli A, Siegel LS. Cognitive functioning as measured by the WISC-R: do children with learning disabilities have distinctive patterns of performance? J Learn Disabil. 2003; 36: 48- 58.
67. Brett EM. Neuroctaneous syndromes In: Brett EM (ed). Pediatric Neurology. London: Churchill Livingstone, 1991: 571- 91.
68. Virdis R, Street ME, Bandello MA, et al. Growth and pubertal disorders in neurofibromatosis type 1. J Pediatr Endocrinol Metab 2003; 16 Suppl 2: 289- 92.
69. Rafia S, Garcia-Pena JJ, Lopez-Pison J, et al. Growth charts for the Spanish population with neurofibromatosis type 1. Rev Neurol 2004; 38: 1009- 12.
70. Roach ES. Neurocutaneous syndromes. Pediatr Clin North Am 1992; 39: 591-620.
71. Santos CC, Kandt RS. Recent advances in neurocutaneous syndromes Curr Opin Pediatr 1990; 2: 1075- 82.
72. Crawford AH, Schorry EK. Neurofibromatosis in children: the role of the orthopaedist. J Am Acad Orthop Surg 1999; 7: 217- 30.
73. Berg OB. Neurocutaneous syndromes: Phakomatoses and allied conditions. In: Swaiman KF (ed). Pediatric Neurology. USA: Mosby, 1994: 1045- 68.
74. Lewis RA, Gerson LP, Axelson KA, et al. Von Recklinghausen neurofibromatosis. II: Incidence of optic gliyoma. Ophthalmology 1984; 91: 929- 36.
75. Kornreich L, Blaser S, Schwarz M, et al. Optic pathway gliyoma: correlation of imaging findings with the presence of neurofibromatosis. R Am J Neuroradiol. 2001; 22: 1963- 9.
76. Hofman KJ, Harris EL, Bryan RN, et al. Neurofibromaosis type-1: the cognitive phenotype. J Pediatr 1994; 124: 1- 8.
77. Kulkantrakorn K, Geller TJ. Seizures in neurofibromatosis 1. Pediatr Neurol 1998; 19: 347- 50.
78. Vivarelli R, Grosso S, Calabrese F, et al. Epilepsy in neurofibromatosis 1. Child Neurol 2003; 18: 338- 42.
79. Clementi M, Battistella PA, Rizzi L, et al. Headache in patients with neurofibromatosis type 1. Headache 1996; 36: 10.
80. DiMario FJ Jr, Langshur S. Headaches in patients with neurofibromatosis-1. J Child Neurol 2000; 15: 235- 8.
81. DeBella K, Poskitt K, Szudek J, et al. Use of "unidentified bright objects" on MRI for diagnosis of neurofibromatosis 1 in children. Neurology 2000; 54: 1646- 51.
82. Aoki SA, Barkovich AJ, Nishimura K. Neurofibromatosis types 1 and 2: cranial MR findings. Radiology 1989; 172: 527- 34
83. Duffner PK, Cohen ME, Seidel FG, et al. The significance of MRI abnormalities in children with neurofibromatosis. Neurology 1989; 39: 373- 8.
84. Bognanno JR, Edwards MK, Lee TA, et al. Cranial MR imaging in neurofibromatosis. Am J Radiol 1988; 151: 381- 8.
85. DiPaola DP, Zimmerman RA, Rorke LB, et al. Neurofibramatosis type 1: pathologic substrate of high-signal-intensity foci of the brain. Radiology 1995; 195: 721- 4.
86. Committee on Genetics Health supervision for children with neurofibromatosis. Pediatrics 1995; 96: 368- 72.
87. Bonawitz C, Castillo Mauricio, Chin CT, et al. Usefulness of contrast material in MR of patients with neurofibromatosis type 1. Am J Neuroradiol Mar;1998 19: 541- 6.
88. Mirowitz SA, Sartor K, Grado M. High-intensity basal ganglia lesions on T1-weighted MR images in neurofibromatosis. Am J Neuroradiol 1989; 10: 1159- 63.
89. Feldmann R, Denecke J, Grenzebach M, et al. Neurofibromatosis type 1: motor and cognitive function and T2-weighted MRI hyperintensities. Neurology. 2003; 61:1 725- 8.
90. Sağlık Bakanlığı İstanbul Göztepe Eğitim ve Araştırma Hastanesi, Çocuk Sağlığı ve Hastalıkları Kliniği, İstanbul
91. Sonomed Tıbbi Görünteleme Merkezi, İstanbul 1.
92. National Institutes of Health Consensus Development Conference.
93. Arch Neurol 1988; 45: 577- 8. 2.
94. Gutmann DH. Recent insights into neurofibromatosis type
95. : clear genetic progress. Arch Neurol 1998; 55: 778- 80. 3.
96. Özmen M. Nörokütan hastalıklar. İçinde: Neyzi O, Ertuğrul
97. T (eds). Pediatri İstanbul: Nobel, 2002: 1368- 72. 4.
98. Steen GR, Taylor JS, Langston JW, et al. Prospective evaluation
99. of the brain in asymptomatic children with neurofibromatosis
100. type 1: relationship of macrocephaly to T1 relaxation changes
101. and structural brain abnormalities. Am J Neuroradiol 2001; 22: 810- 7. 5.
102. Van Es S, North KN, McHugh K, et al. MRI findings in
103. children with neurofibromatosis type 1: a prospective study.
104. Pediatr Radiol 1996; 26: 478- 87. 6.
105. Griffiths PD, Blaser S, Mukonoweshuro W, et al. Neurofibromatosis
106. bright objects in children with neurofibromatosis type 1: a proliferative potential ? Pediatrics 1999; 104: 49. 7. Goldstein SM, Curless RG, Donovan Post MJ, et al. A new sign of neurofibromatosis on magnetic resonance imaging of children. Arch Neurol 1989; 46: 1222- 4. 8. Aoki SA, Barkovich AJ, Nishimura K. Neurofibromatosis types 1 and 2: cranial MR findings. Radiology 1989; 172: 527- 34. 9. North K, Joy P, Yuille D, et al. Spesific learning disability in children with neurofibromatosis type 1: significance of MRI abnormalities. Neurology 1994; 44: 878- 83.
107. Balestri P, Calistri L, Vivarelli R, et al. Central nervous system imaging in reevaluation of patients with neurofibromatosis type 1. Childs Nerv Syst 1993; 9: 448- 51.
108. DiMario FJ, Ramsby G. Magnetic resonance imaging lesion analysis in neurofibromatosis type 1. Arch Neurol 1998; 55: 500- 5.
109. Itoh T, Magnaldi S, White RM, et al. Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities. Am J Neuroradiol 1994; 15: 1513- 9.
110. Kraut MA, Gerring JP, Cooper KL, et al. Longitudinal evolution of unidentified bright objects in children with neurofibromatosis- 1. Am J Med Genet A. 2004; 129: 113- 9.
111. Ferner RE, Chaudhuri R, Bingham J, et al. MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment. J Neurol Neurosurg Psychiatry 1993; 56: 492- 5.
112. Joy P, Roberts C, North K, et al. Neuropsychological function and MRI abnormalities in neurofibromatosis type 1. Dev Med Child Neurol 1995; 37: 906- 14.
113. North KK, Riccardi V, Samango-Sprouse C, et al. Cognitive function and academic performance in neurofibromatosis 1: consensus statement from the NF-1 cognitive disorders task force neurology 1997; 48: 1121- 7.
114. Moore BD, Slopis JM, Schomer D, et al. Neuropsychological significance of areas of high signal intensity on brain MRIs of children with neurofibromatosis. Neurology 1996; 46: 1660- 8.
115. Denckla MB, Hofman K, Mazzocco MM, et al. Relationship between T2-weighted hyperintensities (unidentified bright objects) and lower IQs in children with neurofibromatosis- 1. Am J Med Genet 1996; 67: 98- 102.
116. Ozonoff S. Cognitive impairment in neurofibromatosis type 1. Am J Genet 1999; 89: 45- 52.
117. Goh WH, Khong PL, Leung CS, et al. T2-weighted hyperintensities (unidentified bright objects) in children with neurofibromatosis 1: their impact on cognitive function. J Child Neurol. 2004; 19: 853- 8.
118. Durmazlar N, Ozturk C, Ural B, et al. Turkish children’s performance on Denver II: effect of sex and mother’s education. Dev Med Child Neurol 1998; 40: 411- 6.
119. D'Angiulli A, Siegel LS. Cognitive functioning as measured by the WISC-R: do children with learning disabilities have distinctive patterns of performance? J Learn Disabil. 2003; 36: 48- 58.
120. Brett EM. Neuroctaneous syndromes In: Brett EM (ed). Pediatric Neurology. London: Churchill Livingstone, 1991: 571- 91.
121. Virdis R, Street ME, Bandello MA, et al. Growth and pubertal disorders in neurofibromatosis type 1. J Pediatr Endocrinol Metab 2003; 16 Suppl 2: 289- 92.
122. Rafia S, Garcia-Pena JJ, Lopez-Pison J, et al. Growth charts for the Spanish population with neurofibromatosis type 1. Rev Neurol 2004; 38: 1009- 12.
123. Roach ES. Neurocutaneous syndromes. Pediatr Clin North Am 1992; 39: 591-620.
124. Santos CC, Kandt RS. Recent advances in neurocutaneous syndromes Curr Opin Pediatr 1990; 2: 1075- 82.
125. Crawford AH, Schorry EK. Neurofibromatosis in children: the role of the orthopaedist. J Am Acad Orthop Surg 1999; 7: 217- 30.
126. Berg OB. Neurocutaneous syndromes: Phakomatoses and allied conditions. In: Swaiman KF (ed). Pediatric Neurology. USA: Mosby, 1994: 1045- 68.
127. Lewis RA, Gerson LP, Axelson KA, et al. Von Recklinghausen neurofibromatosis. II: Incidence of optic gliyoma. Ophthalmology 1984; 91: 929- 36.
128. Kornreich L, Blaser S, Schwarz M, et al. Optic pathway gliyoma: correlation of imaging findings with the presence of neurofibromatosis. R Am J Neuroradiol. 2001; 22: 1963- 9.
129. Hofman KJ, Harris EL, Bryan RN, et al. Neurofibromaosis type-1: the cognitive phenotype. J Pediatr 1994; 124: 1- 8.
130. Kulkantrakorn K, Geller TJ. Seizures in neurofibromatosis 1. Pediatr Neurol 1998; 19: 347- 50.
131. Vivarelli R, Grosso S, Calabrese F, et al. Epilepsy in neurofibromatosis 1. Child Neurol 2003; 18: 338- 42.
132. Clementi M, Battistella PA, Rizzi L, et al. Headache in patients with neurofibromatosis type 1. Headache 1996; 36: 10.
133. DiMario FJ Jr, Langshur S. Headaches in patients with neurofibromatosis-1. J Child Neurol 2000; 15: 235- 8.
134. DeBella K, Poskitt K, Szudek J, et al. Use of "unidentified bright objects" on MRI for diagnosis of neurofibromatosis 1 in children. Neurology 2000; 54: 1646- 51.
135. Aoki SA, Barkovich AJ, Nishimura K. Neurofibromatosis types 1 and 2: cranial MR findings. Radiology 1989; 172: 527- 34
136. Duffner PK, Cohen ME, Seidel FG, et al. The significance of MRI abnormalities in children with neurofibromatosis. Neurology 1989; 39: 373- 8.
137. Bognanno JR, Edwards MK, Lee TA, et al. Cranial MR imaging in neurofibromatosis. Am J Radiol 1988; 151: 381- 8.
138. DiPaola DP, Zimmerman RA, Rorke LB, et al. Neurofibramatosis type 1: pathologic substrate of high-signal-intensity foci of the brain. Radiology 1995; 195: 721- 4.
139. Committee on Genetics Health supervision for children with neurofibromatosis. Pediatrics 1995; 96: 368- 72.
140. Bonawitz C, Castillo Mauricio, Chin CT, et al. Usefulness of contrast material in MR of patients with neurofibromatosis type 1. Am J Neuroradiol Mar;1998 19: 541- 6.
141. Mirowitz SA, Sartor K, Grado M. High-intensity basal ganglia lesions on T1-weighted MR images in neurofibromatosis. Am J Neuroradiol 1989; 10: 1159- 63.
142. Feldmann R, Denecke J, Grenzebach M, et al. Neurofibromatosis type 1: motor and cognitive function and T2-weighted MRI hyperintensities. Neurology. 2003; 61:1 725- 8.
143. Sağlık Bakanlığı İstanbul Göztepe Eğitim ve Araştırma Hastanesi, Çocuk Sağlığı ve Hastalıkları Kliniği, İstanbul
144. Sonomed Tıbbi Görünteleme Merkezi, İstanbul 1.
145. National Institutes of Health Consensus Development Conference.
146. Arch Neurol 1988; 45: 577- 8. 2.
147. Gutmann DH. Recent insights into neurofibromatosis type
148. : clear genetic progress. Arch Neurol 1998; 55: 778- 80. 3.
149. Özmen M. Nörokütan hastalıklar. İçinde: Neyzi O, Ertuğrul
150. T (eds). Pediatri İstanbul: Nobel, 2002: 1368- 72. 4.
151. Steen GR, Taylor JS, Langston JW, et al. Prospective evaluation
152. of the brain in asymptomatic children with neurofibromatosis
153. type 1: relationship of macrocephaly to T1 relaxation changes
154. and structural brain abnormalities. Am J Neuroradiol 2001; 22: 810- 7. 5.
155. Van Es S, North KN, McHu gh K, et al. MRI finding s i n
156. children with neurofibromatosis type 1: a prospective study.
157. Pediatr Radiol 1996; 26: 478- 87. 6.
158. Griffiths PD, Blaser S, Mukonoweshuro W, et al. Neurofibromatosis
159. bright objects in children with neurofibromatosis type 1: a proliferative potential ? Pediatrics 1999; 104: 49. 7. Goldstein SM, Curless RG, Donovan Post MJ, et al. A new sign of neurofibromatosis on magnetic resonance imaging of children. Arch Neurol 1989; 46: 1222- 4. 8. Aoki SA, Barkovich AJ, Nishimura K. Neurofibromatosis types 1 and 2: cranial MR findings. Radiology 1989; 172: 527- 34. 9. North K, Joy P, Yuille D, et al. Spesific learning disability in children with neurofibromatosis type 1: significance of MRI ab no rmalities. Neurolog y 199 4; 44: 87 8- 83.
160. Balestri P, Calistri L, Vivarelli R, et al. Central nervous system imaging in reevaluation of patients with neurofibromatosis type 1. Childs Nerv Syst 1993; 9: 448- 51.
161. DiMario FJ, Ramsby G. Magnetic resonance imaging lesion analysis in neurofibromatosis type 1. Arch Neurol 1998; 55: 500- 5.
162. Itoh T, Magnaldi S, White RM, et al. Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities. Am J Neuroradiol 1994; 15: 1513- 9.
163. Kraut MA, Gerring JP, Cooper KL, et al. Longitudinal evolution of unidentified bright objects in children with neurofibromatosis- 1. Am J Med Genet A. 2004; 129: 113- 9.
164. Ferner RE, Chaudhuri R, Bingham J, et al. MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment. J Neurol Neurosurg Psychiatry 1993; 56: 492- 5.
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