title: Differential corticospinal tract degeneration in homozygous 'D90A' SOD-1 ALS and sporadic ALS.
abstract: BACKGROUND
  The homogeneous genotype and stereotyped phenotype of a unique familial form of amyotrophic lateral sclerosis (ALS) (patients homozygous for aspartate-to-alanine mutations in codon 90 (homD90A) superoxide dismutase 1) provides an ideal model for studying genotype/phenotype interactions and pathological features compared with heterogeneous apparently sporadic ALS. The authors aimed to use diffusion tensor tractography to quantify and compare changes in the intracerebral corticospinal tracts of patients with both forms of ALS, building on previous work using whole-brain voxelwise group analysis.
  
  
  METHODS
  21 sporadic ALS patients, seven homD90A patients and 20 healthy controls underwent 1.5&emsp14;T diffusion tensor MRI. Patients were assessed using 'upper motor neuron burden,' El Escorial and ALSFR-R scales. The intracranial corticospinal tract was assessed using diffusion tensor tractography measures of fractional anisotropy (FA), mean diffusivity, and radial and axial diffusivity obtained from its entire length.
  
  
  RESULTS
  Corticospinal tract FA was reduced in sporadic ALS patients compared with both homD90A ALS patients and controls. The diffusion measures in sporadic ALS patients were consistent with anterograde (Wallerian) degeneration of the corticospinal tracts. In sporadic ALS, corticospinal tract FA was related to clinical measures. Despite a similar degree of clinical upper motor neuron dysfunction and disability in homD90A ALS patients compared with sporadic ALS, there were no abnormalities in corticospinal tract diffusion measures compared with controls.
  
  
  CONCLUSIONS
  Diffusion tensor tractography has shown axonal degeneration within the intracerebral portion of the corticospinal tract in sporadic ALS patients, but not those with a homogeneous form of familial ALS. This suggests significant genotypic influences on the phenotype of ALS and may provide clues to slower progression of disease in homD90A patients.
authors.affiliation: Department of Clinical Neuroscience, King’s College London, Institute of Psychiatry, London, UK
authors.forename: C R V
authors.initials: CR
authors.lastname: Blain
authors.forename: S
authors.initials: S
authors.lastname: Brunton
authors.forename: V C
authors.initials: VC
authors.lastname: Williams
authors.forename: A
authors.initials: A
authors.lastname: Leemans
authors.forename: M R
authors.initials: MR
authors.lastname: Turner
authors.forename: P M
authors.initials: PM
authors.lastname: Andersen
authors.forename: M
authors.initials: M
authors.lastname: Catani
authors.forename: B R
authors.initials: BR
authors.lastname: Stanton
authors.forename: J
authors.initials: J
authors.lastname: Ganesalingham
authors.forename: D K
authors.initials: DK
authors.lastname: Jones
authors.forename: S C R
authors.initials: SC
authors.lastname: Williams
authors.forename: P N
authors.initials: PN
authors.lastname: Leigh
authors.forename: A
authors.initials: A
authors.lastname: Simmons
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D016880:Anisotropy; D003062:Codon; D056324:Diffusion Tensor Imaging; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology*; D011712:Pyramidal Tracts / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D003062:Codon; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1