Developmental changes in cerebral white matter microstructure in a disorder of lysosomal storage

Bava, Sunita; Theilmann, Rebecca J.; Sach, Miriam; May, Susanne J.; Frank, Lawrence R.; Hesselink, John R.; Vu, Duc; Trauner, Doris A.

doi:10.1016/j.cortex.2009.03.008

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Volume 46, Issue 2 , Pages 206-216, February 2010

Developmental changes in cerebral white matter microstructure in a disorder of lysosomal storage

Sunita Bava
- Department of Neurosciences, University of California, San Diego, USA
- Department of Radiology, University of California, San Diego, USA
Rebecca J. Theilmann
- Department of Neurosciences, University of California, San Diego, USA
Miriam Sach
- Department of Neurosciences, University of California, San Diego, USA
Susanne J. May
- Department of Neurosciences, University of California, San Diego, USA
- Department of Family and Preventive Medicine, University of California, San Diego, USA
Lawrence R. Frank
- Department of Radiology, University of California, San Diego, USA
- VA San Diego Healthcare System, San Diego, USA
John R. Hesselink
- Department of Radiology, University of California, San Diego, USA
Duc Vu
- Department of Neurosciences, University of California, San Diego, USA
Doris A. Trauner
- Department of Neurosciences, University of California, San Diego, USA
- Department of Pediatrics, University of California, San Diego, USA
- Corresponding author. 9500 Gilman Drive, MC 0935, La Jolla, CA 92093-0935, USA.

Received 6 July 2008; received in revised form 2 February 2009 and 26 February 2009; accepted 3 March 2009. published online 12 May 2009.

Action editor Jordan Grafman

Abstract

The goal of this work was to study white matter (WM) integrity in children with cystinosis, a rare lysosomal storage disorder resulting in cystine accumulation in peripheral and central nervous system tissue. Based on previous reports of cystine crystal formation in myelin precursors as well as evidence for specific cognitive deficits in visuospatial functioning, diffusion tensor imaging (DTI) was applied to 24 children with cystinosis (age 3–7 years) and to 24 typically developing age-matched controls. Scalar diffusion indices, fractional anisotropy (FA) and mean diffusivity (MD), were examined in manually defined regions of interest within the parietal and inferior temporal lobes. Diffusion indices were correlated with performance on measures of visuospatial cognition and with white blood cell cystine levels. Bilaterally decreased FA and increased MD were evident in the inferior and superior parietal lobules in children with cystinosis, with comparable FA and MD to controls in inferior temporal WM, and implicate a dissociation of the dorsal and ventral visual pathways. In older cystinosis children (age>5), diminutions in visuospatial performance were associated with reduced FA in the right inferior parietal lobule. In addition, increased MD was found in the presence of high cystine levels in all children with cystinosis. This study provides new information that the average diffusion properties in children with cystinosis deviate from typically developing children. Findings suggest the presence of early microstructural WM changes in addition to a secondary effect of cystine accumulation. These alterations may impact the development of efficient fiber networks important for visuospatial cognition.