RT Journal Article
SR Electronic
T1 Microstructural Integrity of Cerebral Fiber Tracts in Hereditary Spastic Paraparesis with <em>SPG11</em> Mutation
JF American Journal of Neuroradiology
JO Am. J. Neuroradiol.
FD American Society of Neuroradiology
DO 10.3174/ajnr.A3330
A1 M.-K. Pan
A1 S.-C. Huang
A1 Y.-C. Lo
A1 Chih-Chao Yang
A1 T.-W. Cheng
A1 Chi-Cheng Yang
A1 M.-S. Hua
A1 M.-J. Lee
A1 W.-Y.I. Tseng
YR 2012
UL http://www.ajnr.org/content/early/2012/12/06/ajnr.A3330.abstract
AB BACKGROUND AND PURPOSE: ARHSP-TCC is characterized by progressive leg spasticity, ataxia, and cognitive dysfunction. Although mutations in the human SPG11 gene were identified as responsible for ARHSP-TCC, the cerebral fiber integrity has not been assessed systemically. The objective of this study was to assess cerebral fiber integrity and its clinical significance in patients with ARHSP-TCC. MATERIALS AND METHODS: Five patients from 2 families who were clinically and genetically confirmed to have ARHSP-TCC were examined by neuropsychological evaluation and DSI of the brain. We performed voxel-based GFA analysis for global white matter evaluation, tractography-based analysis for tract-to-tract comparisons, and tract-specific analysis of the CST to evaluate microstructural integrity along the axonal direction. RESULTS: The neuropsychological evaluation revealed widespread cognitive decline across all domains. Voxel-based analysis showed global reduction of GFA in the cerebral white matter. Tractography-based analysis revealed a significant reduction of the microstructural integrity in all neural fiber types, while commissure and association fibers had more GFA reduction than projection fibers (P &lt; .00001). Prefrontal and motor portions of the CC were most severely affected among all fiber tracts (P &lt; .00001, P = .018). Tract-specific analysis of the CST validated a “dying-back” phenomenon (R2 = 0.68, P &lt; .00001). CONCLUSIONS: There was a characteristic gradation in the reduction of microstructural integrity among fiber types and within the CC in patients with the SPG11 mutation. The dying-back process in CST might explain the pathogenic mechanisms for ARHSP-TCC. Abbreviations ARHSP-TCCautosomal recessive hereditary spastic paraparesis with thin corpus callosumCCcorpus callosumCSTcorticospinal tractDSIdiffusion spectrum imagingGFAgeneralized fractional anisotropy