Brain MR imaging in patients with lower motor neuron-predominant disease

Purpose: To investigate the patterns of cortical thinning and white matter tract damage in patients with lower motor neuron (LMN)-predominant disease compared with healthy control subjects and those with classic amyotrophic lateral sclerosis (ALS) and to evaluate the relationship between brain structural changes and clinical and cognitive features in these patients. Materials and Methods: This study was approved by the local ethical committee, and written informed consent was obtained from all subjects before enrollment. Twenty-eight patients with LMNpredominant disease were compared with 55 patients with ALS and 56 healthy control subjects. Patients underwent a clinical and neuropsychological assessment and T1-weighted and diffusion-tensor magnetic resonance (MR) imaging. Surface-based morphometry was used to assess cortical thickness. Tract-based spatial statistics and tractography were used to study white matter tract damage. Results: Patients with LMN-predominant disease did not show differences compared with healthy control subjects in cortical thickness and diffusion-tensor MR imaging metrics. Patients with ALS showed cortical thinning of the motor-related cortices and a distributed involvement of the prefrontal, temporal, and parietal gyri (P <.05, false discovery rate corrected). Patients with ALS also showed white matter damage along motor and extramotor tracts compared with control subjects and patients with LMN-predominant disease (tract-based spatial statistics: P <.05, family-wise error corrected; tractography: P values <.001 to.05, false discovery rate corrected). In patients with LMN-predominant disease, cognitive deficits correlated with alterations in diffusivity in the left cingulum (r = 20.66, P =.01) and superior longitudinal fasciculus (r = 20.65, P =.05). Conclusion: Motor and extramotor cortical thinning and diffusion-tensor MR imaging alterations were specific for motor neuron disease phenotypes, with clinically overt upper motor neuron involvement. However, the lack of significant differences in cortical thickness between subjects with LMNpredominant disease and those with ALS and cognitive deficits associated with alterations in diffusivity in patients with LMN-predominant disease suggest that investigating brain structural and microstructural MR imaging features may provide markers of central nervous system damage in patients with rare motor neuron disease.