Corticoefferent pathways in pure lower motor neuron disease: a diffusion tensor imaging study

Criteria for assessing upper motor neuron pathology in lower motor neuron disease (LMND) still remain major issues in clinical diagnosis. This study was designed to investigate patients with the clinical diagnosis of adult pure LMND by use of whole brain based diffusion tensor imaging (DTI) to delineate alterations of corticoefferent pathways in vivo. Comparison of fractional anisotropy (FA) maps was performed by whole brain-based spatial statistics for 37 LMND patients vs. 53 matched controls to detect white matter structural alterations. LMND patients were clinically differentiated in fast and slow progressors. Furthermore, tract specific alterations were investigated by fiber tracking techniques according to the staging hypothesis for amyotrophic lateral sclerosis (ALS). The analysis of white matter structural connectivity demonstrated widespread and characteristic patterns of alterations in patients with LMND, predominantly along the corticospinal tract (CST), with multiple clusters of regional FA reductions in the motor system at p < 0.05 (corrected for multiple comparisons). Fast progressing LMND showed substantial CST involvement, while slow progressors showed less CST alterations. In the tract-specific analysis according to the ALS-staging pattern as suggested by Braak, fast progressing LMND showed significant alterations of ALS-related tract systems beyond the CST compared to slow progressors and controls. In clinically pure LMND patients, the involvement of corticoefferent fibers was demonstrated, in particular along the CST, supporting the hypothesis that LMND is a phenotypical variant of ALS. This finding suggests to treat these patients like ALS, including the opportunity to participate in clinical trials.