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PT  - JOURNAL ARTICLE
AU  - Pan, M.-K.
AU  - Huang, S.-C.
AU  - Lo, Y.-C.
AU  - Yang, Chih-Chao
AU  - Cheng, T.-W.
AU  - Yang, Chi-Cheng
AU  - Hua, M.-S.
AU  - Lee, M.-J.
AU  - Tseng, W.-Y.I.
TI  - Microstructural Integrity of Cerebral Fiber Tracts in Hereditary Spastic Paraparesis with &lt;em&gt;SPG11&lt;/em&gt; Mutation
AID  - 10.3174/ajnr.A3330
DP  - 2013 May 01
TA  - American Journal of Neuroradiology
PG  - 990--996
VI  - 34
IP  - 5
4099  - http://www.ajnr.org/content/34/5/990.short
4100  - http://www.ajnr.org/content/34/5/990.full
SO  - Am. J. Neuroradiol.2013 May 01; 34
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 &amp;lt; .00001). Prefrontal and motor portions of the CC were most severely affected among all fiber tracts (P &amp;lt; .00001, P = .018). Tract-specific analysis of the CST validated a “dying-back” phenomenon (R2 = 0.68, P &amp;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. ARHSP-TCCautosomal recessive hereditary spastic paraparesis with thin corpus callosumCCcorpus callosumCSTcorticospinal tractDSIdiffusion spectrum imagingGFAgeneralized fractional anisotropy