Natural History of Canavan Disease Revealed by Proton Magnetic Resonance Spectroscopy (1H‐MRS) and Diffusion-weighted MRI

C. G. Janson; S. W. J. McPhee; J. Francis; D. Shera; M. Assadi; A. Freese; P. Hurh; J. Haselgrove; D. J. Wang; L. Bilaniuk; P. Leone

doi:10.1055/s-2006-924734

Neuropediatrics 2006; 37(4): 209-221
DOI: 10.1055/s-2006-924734

Rapid Communication

Natural History of Canavan Disease Revealed by Proton Magnetic Resonance Spectroscopy (¹H‐MRS) and Diffusion-weighted MRI

C. G. Janson¹ ^, ² ^, ⁵ , S. W. J. McPhee¹ , J. Francis¹ , D. Shera⁴ , M. Assadi² , A. Freese⁵ , P. Hurh³ , J. Haselgrove³ , D. J. Wang³ , L. Bilaniuk³ , P. Leone¹

¹UMDNJ-Robert Wood Johnson Medical School, Dept. of Neurosurgery, Camden, NJ, United States
²UMDNJ-Robert Wood Johnson Medical School, Dept. of Neurology, Camden, NJ, United States
³Children's Hospital of Philadelphia, Dept. of Neuroradiology, Philadelphia, PA, United States
⁴Children's Hospital of Philadelphia, Dept. of Biostatistics, Philadelphia, PA, United States
⁵University of Minnesota, Department of Neurosurgery, Minneapolis, MN, United States

Abstract

Canavan disease is a childhood leukodystrophy caused by mutations in the gene for human aspartoacylase (ASPA), which leads to an abnormal accumulation of the substrate molecule N-acetyl-aspartate (NAA) in the brain. This study was designed to model the natural history of Canavan disease using MRI and proton magnetic resonance spectroscopy (¹H-MRS). NAA and various indices of brain structure (morphology, quantitative T1, fractional anisotropy, apparent diffusion coefficient) were measured in white and gray matter regions during the progression of Canavan disease. A mixed-effects statistical model was used to fit all outcome measures. Longitudinal data from 28 Canavan patients were directly compared in each brain region with reference data obtained from normal, age-matched pediatric subjects. The resultant model can be used to non-invasively monitor the natural history of Canavan disease or related leukodystrophies in future studies involving drug, gene therapy, or stem cell treatments.

Key words

Canavan disease - leukodystrophy - pediatric - brain - spectroscopy - magnetic resonance - NAA

Full Text

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Christopher G. Janson, MD

The National Endowment for Alzheimer's Research

Box 772

Fairfield, CT 06824

USA

Email: janson@memorymatters.org