Download PDF
Neuropediatrics 2006; 37(4): 241-246
DOI: 10.1055/s-2006-924722
Original Article

Georg Thieme Verlag KG Stuttgart · New York

Proton MR Spectroscopic Imaging in Ataxia-Telangiectasia

D. D. M. Lin1 , T. O. Crawford2 , 3 , H. M. Lederman3 , 4 , P. B. Barker1 , 5
  • 1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
  • 2Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
  • 3Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
  • 4Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
  • 5F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA
Further Information

Publication History

Received: March 13, 2006

Accepted after Revision: September 18, 2006

Publication Date:
20 December 2006 (online)

    Permissions and Reprints

Abstract

Object: Ataxia-telangiectasia (A-T) is a recessively inherited neurodegenerative disorder with prominent progressive ataxia and cerebellar degeneration, as well as manifest abnormalities of tone, posture, and movement suggesting extrapyramidal dysfunction. In this study, we tested the hypothesis that regional metabolite levels, as measured by proton magnetic resonance spectroscopic imaging, would be abnormal in patients with A-T in the posterior fossa and basal ganglia, reflecting the underlying neurodegenerative processes in these regions. Methods: Spectroscopic images of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were obtained in 8 patients with A-T and 8 age-matched controls. Normalized metabolite levels were compared between A-T patients and control subjects in various regions of interest, including the cerebellum, brainstem, and basal ganglia. Results: A-T patients were distinguished from controls by the profound loss of all metabolites in the cerebellar vermis (NAA, p < 0.01; Cr and Cho, p < 0.05) and a trend for decreased metabolites within the cerebellar hemispheres. No abnormalities were detected in the basal ganglia. Conclusions: Proton MR spectroscopic features in A-T closely correlate with the morphologic neuroimaging findings of posterior fossa atrophy. Although symptoms suggesting extrapyramidal dysfunction are part of the A-T phenotype, these are not associated with altered metabolite levels in the basal ganglia.

Key words

Ataxia-Telangiectasia - brain - magnetic resonance imaging - magnetic resonance spectroscopy - metabolism

References

  • 1 Cabana M D, Crawford T O, Winkelstein J A, Christensen J R, Lederman H M. Consequences of the delayed diagnosis of ataxia-telangiectasia.  Pediatrics. 1998;  102 98-100
    CrossrefPubMedGoogle Scholar
  • 2 Chun H H, Gatti R A. Ataxia-telangiectasia, an evolving phenotype.  DNA Repair (Amst). 2004;  3 1187-1196
    CrossrefPubMedGoogle Scholar
  • 3 Chung E O, Bodensteiner J B, Noorani P A, Schochet Jr S S. Cerebral white-matter changes suggesting leukodystrophy in ataxia telangiectasia.  J Child Neurol. 1994;  9 31-35
    PubMedGoogle Scholar
  • 4 Churchyard A, Stell R, Mastaglia F L. Ataxia telangiectasia presenting as an extrapyramidal movement disorder and ocular motor apraxia without overt telangiectasia.  Clin Exp Neurol. 1991;  28 90-96
    PubMedGoogle Scholar
  • 5 Ciemins J J, Horowitz A L. Abnormal white matter signal in ataxia telangiectasia.  Am J Neuroradiol. 2000;  21 1483-1485
    PubMedGoogle Scholar
  • 6 Crawford T O. Ataxia telangiectasia.  Semin Pediatr Neurol. 1998;  5 287-294
    CrossrefPubMedGoogle Scholar
  • 7 Crawford T O, Mandir A S, Lefton-Greif M A. et al . Quantitative neurologic assessment of ataxia-telangiectasia.  Neurology. 2000;  54 1505-1509
    CrossrefPubMedGoogle Scholar
  • 8 Farina L, Uggetti C, Ottolini A. et al . Ataxia-telangiectasia: MR and CT findings.  J Comput Assist Tomogr. 1994;  18 724-727
    CrossrefPubMedGoogle Scholar
  • 9 Goyal V, Behari M. Dystonia as presenting manifestation of ataxia telangiectasia: a case report.  Neurol India. 2002;  50 187-189
    PubMedGoogle Scholar
  • 10 Griffiths P. Brain Scanning Technologies. International Conference on the Clinical Science of Ataxia-Telangiectasia. University of Birmingham, Birmingham, UK October 14 - 15, 2005. 
    Google Scholar
  • 11 Jacobs M A, Horska A, van Zijl P C, Barker P B. Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain stem.  Magn Reson Med. 2001;  46 699-705
    CrossrefPubMedGoogle Scholar
  • 12 Koepp M, Schelosky L, Cordes I, Cordes M, Poewe W. Dystonia in ataxia telangiectasia: report of a case with putaminal lesions and decreased striatal [123I]iodobenzamide binding.  Mov Disord. 1994;  9 455-459
    CrossrefPubMedGoogle Scholar
  • 13 Lucato L T, Otaduy M C, Barbosa E R. et al . Proton MR spectroscopy in Wilson disease: analysis of 36 cases.  Am J Neuroradiol. 2005;  26 1066-1071
    PubMedGoogle Scholar
  • 14 McConville C M, Stankovic T, Byrd P J. et al . Mutations associated with variant phenotypes in ataxia-telangiectasia.  Am J Hum Genet. 1996;  59 320-330
    PubMedGoogle Scholar
  • 15 O'Neill J, Schuff N, Marks Jr W J, Feiwell R, Aminoff M J, Weiner M W. Quantitative 1H magnetic resonance spectroscopy and MRI of Parkinson's disease.  Mov Disord. 2002;  17 917-927
    CrossrefPubMedGoogle Scholar
  • 16 Reynolds Jr N C, Prost R W, Mark L P. Heterogeneity in 1H‐MRS profiles of presymptomatic and early manifest Huntington's disease.  Brain Res. 2005;  1031 82-89
    CrossrefPubMedGoogle Scholar
  • 17 Sardanelli F, Parodi R C, Ottonello C. et al . Cranial MRI in ataxia-telangiectasia.  Neuroradiology. 1995;  37 77-82
    CrossrefPubMedGoogle Scholar
  • 18 Savitsky K, Bar-Shira A, Gilad S. et al . A single ataxia telangiectasia gene with a product similar to PI‐3 kinase.  Science. 1995;  268 1749-1753
    CrossrefPubMedGoogle Scholar
  • 19 Segewick R P, Boder E. Ataxia-telangiectasia. de Jong JMJV Handbook of Clinical Neurology. Ataxia-telangiectasia. Amsterdam; Elsevier 1991 60: 347-423
    Google Scholar
  • 20 Sun X, Becker-Catania S G, Chun H H. et al . Early diagnosis of ataxia-telangiectasia using radiosensitivity testing.  J Pediatr. 2002;  140 724-731
    CrossrefPubMedGoogle Scholar
  • 21 Tavani F, Zimmerman R A, Berry G T, Sullivan K, Gatti R, Bingham P. Ataxia-telangiectasia: the pattern of cerebellar atrophy on MRI.  Neuroradiology. 2003;  45 315-319
    PubMedGoogle Scholar
  • 22 Watanabe H, Fukatsu H, Katsuno M. et al . Multiple regional 1H‐MR spectroscopy in multiple system atrophy: NAA/Cr reduction in pontine base as a valuable diagnostic marker.  J Neurol Neurosurg Psychiatry. 2004;  75 103-109
    PubMedGoogle Scholar

M.D. Ph.D. Doris D. M. Lin

Division of Neuroradiology
The Johns Hopkins University School of Medicine

600 North Wolfe Street

Baltimore, MD 21287

USA

Email: ddmlin@jhmi.edu

      >