Diffusion tensor imaging in sporadic and familial (D90A SOD1) forms of amyotrophic lateral sclerosis.

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.