Background: The basis of heterogeneity in the clinical presentation and rate of progression of amyotrophic lateral sclerosis (ALS) is poorly understood.
Objectives: To use diffusion tensor imaging as a measure of axonal pathologic features in vivo in ALS and to compare a homogeneous form of familial ALS (homozygous D90A SOD1 [superoxide dismutase 1]) with sporadic ALS.
Design: Cross-sectional diffusion tensor imaging study.
Setting: Tertiary referral neurology clinic.
Patients: Twenty patients with sporadic ALS, 6 patients with homozygous D90A SOD1 ALS, and 21 healthy control subjects.
Main outcome measure: Fractional anisotropy in cerebral white matter.
Results: Patients with homozygous D90A SOD1 ALS showed less extensive pathologic white matter in motor and extramotor pathways compared with patients with sporadic ALS, despite similar disease severity assessed clinically using a standard functional rating scale. Fractional anisotropy correlated with clinical measures of severity and upper motor neuron involvement.
Conclusion: In vivo diffusion tensor imaging measures demonstrate differences in white matter degeneration between sporadic ALS and a unique familial form of the disease, indicating that genotype influences the distribution of cerebral pathologic features in ALS.