Pediatric Radiology

, Volume 36, Issue 10, pp 1048–1056 | Cite as

Age-related findings on MRI in neurofibromatosis type 1

  • Deepak S. Gill
  • Shelley L. Hyman
  • Adam Steinberg
  • Kathryn N. North
Original Article

Abstract

Background

T2 hyperintensities (T2H) on MRI are the most common CNS lesions in individuals with neurofibromatosis type 1 (NF1).

Objectives

The aim was to determine the frequency, signal characteristics and localization of T2H at different ages. In addition, we examined the sensitivity of different MR imaging sequences in detecting these lesions.

Materials and methods

We studied prospectively a cohort of children, adolescents and young adults with NF1 using T2-volume (T2-V) and conventional MRI sequences. Lesions were designated as either discrete or diffuse, and the region of signal abnormality was recorded. A total of 103 patients were studied (age range 8.0–25.4 years, mean 13.9 years).

Results

The frequency, size, and intensity of T2H decreased with age in the basal ganglia (BG) and the cerebellum/brainstem (CB/BS). The majority of thalamic and CB/BS lesions were diffuse. Of the total cohort, 80% had diffuse bilateral hippocampal hyperintensities and 18.4% had hemispheric lesions best demonstrated on FLAIR; there was no significant difference in the frequency or signal intensity of hemispheric lesions with age.

Conclusion

Lesions in the cerebral hemispheres and hippocampus imaged by MR do not change in prevalence over time, suggesting a different pathological basis from the lesions in the in BG and CB/BS that resolve with age. FLAIR and T2-V sequences are more sensitive in detecting lesions than standard T2-weighted sequences.

Keywords

Neurofibromatosis type 1 MRI Hippocampus 

Notes

Acknowledgements

This research was supported by the Department of Defense Neurofibromatosis Research Program, managed by the U.S. Army Medical Research and Materiel Command (USAMRMC; award number DAMD17-00-1-0534). We are grateful to Dr. Sridhar Gibikote for his helpful comments on the significance of the radiological findings and Mrs. Susanne Smith for her administrative support.

References

  1. 1.
    DiPaolo DP, Zimmerman RA, Rorke LB, et al (1995) Neurofibromatosis type 1: pathologic substrate of high-signal intensity foci in the brain. Radiology 195:721–724PubMedGoogle Scholar
  2. 2.
    Cawthon RM, Weiss M, Xu G, et al (1990) A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell 62:193–201PubMedCrossRefGoogle Scholar
  3. 3.
    Wallace MR, Marchuk DA, Andersen LB, et al (1990) Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249:181–186PubMedCrossRefGoogle Scholar
  4. 4.
    Xu G, O’Connell P, Viskochil D, et al (1990) The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62:599–608PubMedCrossRefGoogle Scholar
  5. 5.
    DeClue JE, Cohen BD, Lowy DR (1991) Identification and characterization of the neurofibromatosis type 1 gene product. Proc Natl Acad Sci U S A 88:9914–9918PubMedCrossRefGoogle Scholar
  6. 6.
    Gutmann DH, Wood DL, Collins FS (1991) Identification of the neurofibromatosis type 1 gene product. Proc Natl Acad Sci U S A 88:9658–9662PubMedCrossRefGoogle Scholar
  7. 7.
    North K, Ratner N (2003) The brain in neurofibromatosis type 1. In: Fisch GS (ed) Genetics and genomics of neurobehavioural disorders in contemporary clinical neurosciences series. Humana Press, Totowa, pp 97–135Google Scholar
  8. 8.
    Moore BD III, Slopis JM, Jackson EF, et al (2000) Brain volume in children with neurofibromatosis type 1: relation to neuropsychological status. Neurology 54:914–920PubMedGoogle Scholar
  9. 9.
    Kayl AE, Moore BD III, Slopis JM, et al (2000) Quantitative morphology of the corpus callosum in children with neurofibromatosis and attention-deficit hyperactivity disorder. J Child Neurol 15:90–96PubMedGoogle Scholar
  10. 10.
    Sevick RJ, Barkovich AJ, Edwards MSB, et al (1992) Evolution of white matter lesions in neurofibromatosis type 1: MR findings. AJNR 159:171–175Google Scholar
  11. 11.
    North KN, Riccardi MD, Samango-Sprouse C, et al (1997) Cognitive function and academic performance in neurofibromatosis 1: consensus statement from the NF1 Cognitive Disorders Task Force. Neurology 48:1121–1127PubMedGoogle Scholar
  12. 12.
    Aoki S, Barkovich AJ, Nishimura K, et al (1989) Neurofibromatosis type 1 and 2: cranial MR findings. Radiology 172:527–534PubMedGoogle Scholar
  13. 13.
    DeBella K, Poskitt K, Szudek J, et al (2000) Use of “unidentified bright objects” on MRI for diagnosis of neurofibromatosis 1 in children. Neurology 54:1646–1650PubMedGoogle Scholar
  14. 14.
    Van Es S, North KN, McHugh K, et al (1996) MRI findings in children with neurofibromatosis type 1: a prospective study. Pediatr Radiol 26:478–487PubMedCrossRefGoogle Scholar
  15. 15.
    Rosman NP, Pearce J (1967) The brain in multiple neurofibromatosis (von Recklinghausen’s disease): a suggested neuropathological basis for the associated mental defect. Brain 90:829–838PubMedCrossRefGoogle Scholar
  16. 16.
    Rubinstein LJ (1986) The malformative central nervous system lesions in the central and peripheral forms of neurofibromatosis: a neuropathological study of 22 cases. Ann N Y Acad Sci 486:14–29PubMedCrossRefGoogle Scholar
  17. 17.
    Itoh T, Magnaldi S, White RM, et al (1994) Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities. AJNR 15:1513–1519PubMedGoogle Scholar
  18. 18.
    Hyman SL, Gill DS, Shores EA, et al (2003) Natural history of cognitive deficits and their relationships to MRI T2-hyperintensities in NF1. Neurology 60:1139–1145PubMedGoogle Scholar
  19. 19.
    Mirowitz SA, Sartor K, Gado M (1989) High-intensity basal ganglia lesion on T1 weighted MR images in neurofibromatosis type-1. AJNR 10:1159–1163PubMedGoogle Scholar
  20. 20.
    Steen RG, Taylor JS, Langston JW, et al (2001) Prospective evaluation of the brain in asymptomatic children with neurofibromatosis type 1: relationship of macrocephaly to T1 relaxation changes and structural brain abnormalities. AJNR 22:810–817PubMedGoogle Scholar
  21. 21.
    Terada H, Barkovich AJ, Edwards MSB, et al (1996) Evolution of high-intensity basal ganglia lesions on T1-weighted MR in neurofibromatosis type 1. AJNR 17:755–760PubMedGoogle Scholar
  22. 22.
    Ferner RE, Chaudhuri R, Bingham J, et al (1993) MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment. J Neurol Neurosurg Psychiatry 56:492–495PubMedCrossRefGoogle Scholar
  23. 23.
    Balestri P, Vivarelli R, Grosso S, et al (2003) Malformations of cortical development in neurofibromatosis type 1. Neurology 61:1799–1801PubMedGoogle Scholar
  24. 24.
    Yamanouchi H, Kato T, Matsuda H, et al (1995) MRI in neurofibromatosis type I: using fluid-attenuated inversion recovery pulse sequences. Pediatr Neurol 12:286–290PubMedCrossRefGoogle Scholar
  25. 25.
    Silva AJ, Frankland PW, Marowitz Z, et al (1997) A mouse model for the learning and memory deficits associated with neurofibromatosis type I. Nat Genet 15:281–284PubMedCrossRefGoogle Scholar
  26. 26.
    Legius E, Marchuk DA, Collins FS, et al (1993) Somatic deletion of neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis. Nat Genet 3:122–126PubMedCrossRefGoogle Scholar
  27. 27.
    Shannon KM, O’Connell P, Martin GA, et al (1994) Loss of the normal NF1 allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders. N Engl J Med 330:597–601PubMedCrossRefGoogle Scholar
  28. 28.
    Bollag G, McCormick F (1991) Differential regulation of Ras GAP and neurofibromatosis gene product activities. Nature 351:576–579PubMedCrossRefGoogle Scholar
  29. 29.
    Nordlund ML, Rizvi TA, Brannan CI, et al (1995) Neurofibromin expression and astrogliosis in neurofibromatosis (type 1) brains. J Neuropathol Exp Neurol 54:588–600PubMedGoogle Scholar
  30. 30.
    Hofman KJ, Harris EL, Bryan RN, et al (1994) Neurofibromatosis type 1: the cognitive phenotype. J Pediatr 124:S1–S8PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Deepak S. Gill
    • 1
  • Shelley L. Hyman
    • 2
  • Adam Steinberg
    • 3
  • Kathryn N. North
    • 1
    • 2
  1. 1.The T. Y. Nelson Department of NeurologyThe Children’s Hospital at WestmeadSydneyAustralia
  2. 2.Neurogenetics Research UnitThe Children’s Hospital at WestmeadSydneyAustralia
  3. 3.Department of RadiologyThe Children’s Hospital at WestmeadSydneyAustralia

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