Abnormal diffusion tensor in nonsymptomatic familial amyotrophic lateral sclerosis with a causative superoxide dismutase 1 mutation

Purpose: To determine whether diffusion abnormalities can be observed in nonsymptomatic family members with a known causative Cu/Zn superoxide dismutase mutation (asymptomatic familial amyotrophic lateral sclerosis; AFALS ^+SOD1) in a family with autosomal dominant familial amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). Materials and Methods: A total of eight AFALS^+SOD1 subjects (aged 17-43 years) were age-matched with 13 healthy controls (aged 19-45 years) without SOD1 mutations. DTI was carried out on a 1.5T scanner. The diffusion index maps derived were then normalized spatially for voxel-based analysis, region of interest (ROI)-based analysis was also carried out. Results: Our voxel-based and ROI-based analysis showed that AFALS^+SOD1 subjects have decreased fractional anisotropy (FA) (0.5401 vs. 0.5168, P < 0.05) and increased tensor trace (TT) (2.5854 × 10^-3 mm²/second vs. 2.6226 × 10^-3 mm²/second, P < 0.04) at the posterior limb of the internal capsule compared to the control subjects. Increased radial diffusivity (E_(2,3)/2) was detected on both sides (right = 0.5710 × 10^-3 mm²/second vs. 0.5943 × 10^-3 mm²/second, P < 0.05; left = 0.5666 × 10^-3 mm²/second vs. 0.5872 × 10^-3 mm²/second, P < 0.05). No significant change in axial diffusivity (E₁) was detected. Conclusion: Abnormal diffusivity was found at the posterior limb of the internal capsule in AFALS^+SOD1 subjects, hitherto unreported. Our results suggest that DTI may detect diffusion abnormalities in AFALS ^+SOD1 subjects before symptoms develop.