title: Microstructural integrity of cerebral fiber tracts in hereditary spastic paraparesis with SPG11 mutation.
abstract: OBJECTIVE
  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.
  
  
  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 (R(2) = 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.
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: M-K
authors.initials: MK
authors.lastname: Pan
authors.forename: S-C
authors.initials: SC
authors.lastname: Huang
authors.forename: Y-C
authors.initials: YC
authors.lastname: Lo
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Yang
authors.forename: T-W
authors.initials: TW
authors.lastname: Cheng
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Yang
authors.forename: M-S
authors.initials: MS
authors.lastname: Hua
authors.forename: M-J
authors.initials: MJ
authors.lastname: Lee
authors.forename: W-Y I
authors.initials: WY
authors.lastname: Tseng
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics*; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology*
chemical_list: D011506:Proteins; C520412:SPG11 protein, human