Linear Longitudinal Decline in Fractional Anisotropy in Patients with Amyotrophic Lateral Sclerosis

As potential therapies aimed at halting or slowing the decline in upper motor neuron function in patients with amyotrophic lateral sclerosis (ALS) or primary lateral sclerosis (PLS) are developed, a quantitative method for monitoring response will be necessary. Measurement of fractional anisotropy (FA) using diffusion tensor imaging (DTI) over time should parallel functional decline from upper motor neuron degeneration in these patients. Two patients with definite ALS were imaged at 3.0 T and FA values were obtained in the corticospinal tract every 3 months for 1 year. The FA values were compared to normal age-matched controls. Both patients showed linear decreases in FA values over time with R2 values ranging from 0.93 to 0.99. The decline became statistically significant over the course of the study. Qualitative decreases in anisotropy were also evident on FA maps. If these trends can be validated in greater numbers of patients, DTI may serve as an objective quantitative biomarker for disease progression in patients with upper motor neuron disease.