Brain Structural Analysis of Korean ALS patients using Diffusion Tensor Imaging and Voxel Based Morphometry : It is not all what we think

초록

BACKGROUND and OBJECTIVES Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that has sporadic and inherited forms. Although the degeneration predominantly affects the motor system, cognitive and behavioral dysfunctions have been described for over a century. There have been objective evidences that ALS is an inhomogeneous disease entity with various cognitive-behavior symptoms overlapping typical motor deficits in clinical, radiological, pathological, and genetic aspects . Our purpose is to assess subtle structural brain changes using diffusion tensor images (DTI) and Voxel based morphometry(VBM) in Asian ALS patients compared to normal brain. METHODS We analyzed neuroimaing findings of 38 consecutive patients with motor neuron disease in our ALS clinic using 3.0 Tesla MRI and compared to 47 age-matched healthy controls. We also investigated their spatial characteristics of brain. Patients with sporadic ALS (male:19, female : 20) with clinical and electrophysiological evidence of combined upper and lower motor neuron involvement in at least one region (Revised El Escorial Criteria for clinically probable or definite ALS) and healthy age-matched controls (men, women) were recruited. Cognitive function was evaluated with the Korean version of Mini Mental State Exam and neuropsychological test. Voxel-based analysis and quantitative comparisons of the diffusion parameters between ALS patients and controls were performed. Correlation analyses of diffusion parameters and disease duration and disease severity were performed. RESULTS: In analysis of DTI, the FA values of ALS patients without any cognitive dysfunctions are lower in corticospinal tract but higher in the subcortical structures compared to normal healthy controls regardless of disease subtype(<0.0001). In contrast, the FA values of subcortical structures are lower than normal in all patients with cognitive dysfunction. Patients showed a gray matter volume decrease in several frontal and temporal areas bilaterally (P <0 .001 uncorrected) compared with controls, with a slight prevalence in the right hemisphere. No volume reduction in primary motor cortices of patients was detected in VBM study. CONCLUSIONS: This was the first large scale study of Korean ALS patients in one center using high Tesla MRI and neuropsychological test. It has been accepted that the ALS is a heterogeneous disease entity groups. It is to be hoped that this results will contribute to convert the classical concept of ALS and to bring active research for discovering disease origin.