%0 Journal Article %A M.-K. Pan %A S.-C. Huang %A Y.-C. Lo %A Chih-Chao Yang %A T.-W. Cheng %A Chi-Cheng Yang %A M.-S. Hua %A M.-J. Lee %A W.-Y.I. Tseng %T Microstructural Integrity of Cerebral Fiber Tracts in Hereditary Spastic Paraparesis with SPG11 Mutation %D 2013 %R 10.3174/ajnr.A3330 %J American Journal of Neuroradiology %P 990-996 %V 34 %N 5 %X 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 < .00001). Prefrontal and motor portions of the CC were most severely affected among all fiber tracts (P < .00001, P = .018). Tract-specific analysis of the CST validated a “dying-back” phenomenon (R2 = 0.68, P < .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. ARHSP-TCCautosomal recessive hereditary spastic paraparesis with thin corpus callosumCCcorpus callosumCSTcorticospinal tractDSIdiffusion spectrum imagingGFAgeneralized fractional anisotropy %U https://www.ajnr.org/content/ajnr/34/5/990.full.pdf