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


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 x 10(-3) mm(2)/second vs. 2.6226 x 10(-3) mm(2)/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 x 10(-3) mm(2)/second vs. 0.5943 x 10(-3) mm(2)/second, P < 0.05; left = 0.5666 x 10(-3) mm(2)/second vs. 0.5872 x 10(-3) mm(2)/second, P < 0.05). No significant change in axial diffusivity (E(1)) was detected.


CONCLUSIONS
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.
Ng
Man-Cheuk
MC
Department of Orthopaedics and Traumatology, University of Hong Kong, Hong Kong.
Ho
Jenny Ting
JT
Ho
Shu-Leong
SL
Lee
Raymand
R
Li
Geng
G
Cheng
Tat-Sun
TS
Song
You-Qiang
YQ
Ho
Philip Wing-Lok
PW
Fong
Gardian Chung-Yan
GC
Mak
Windsor
W
Chan
Koon-Ho
KH
Li
Leonard Sheung-Wai
LS
Luk
Keith Dip-Kei
KD
Hu
Yong
Y
Ramsden
David Boyer
DB
Leong
Lilian Ling-Yee
LL
D000293:Adolescent; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D016880:Anisotropy; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009154:Mutation; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1