MING-KAI PANHuang S.-C.Lo Y.-C.CHIH-CHAO YANGCheng T.-W.Hua M.-S.MING-JEN LEEWEN-YIH TSENGYang T.-W.2020-03-032020-03-032013-050195-6108https://www.scopus.com/inward/record.uri?eid=2-s2.0-84878477436&doi=10.3174%2fajnr.A3330&partnerID=40&md5=c6fd822e31b47a1fb652ebdfc78a7d2bhttps://scholars.lib.ntu.edu.tw/handle/123456789/468739BACKGROUND 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.[SDGs]SDG3muscle protein; SPGII protein; unclassified drug; adult; article; autosomal recessive hereditary spastic paraparesis with thin corpus callosum; brain; brain commissure; clinical article; clinical assessment; cognitive defect; controlled study; corpus callosum; corpus callosum agenesis; diagnostic test accuracy study; diffusion spectrum imaging; diffusion weighted imaging; family; female; fractional anisotropy; gene expression; gene mutation; generalized fractional anisotropy; genetic analysis; hereditary motor sensory neuropathy; human; male; motor cortex; nerve fiber; nerve projection; neuroimaging; neuropsychological test; predictive value; prefrontal cortex; pyramidal tract; tractography; voxel based morphometry; white matter; Adult; Brain; Cognition Disorders; Diffusion Tensor Imaging; Female; Genetic Predisposition to Disease; Humans; Male; Mutation; Nerve Fibers, Myelinated; Polymorphism, Single Nucleotide; Proteins; Spastic Paraplegia, Hereditaryjournal article10.3174/ajnr.A3330232219522-s2.0-84878477436