Brain Structural Analysis of Korean ALS patients using Voxel Based Morphometry

Abstract

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 . Demographics, respiratory status, bulbar site of onset, and disease severity are potential risk factors for cognitive impairment in ALS. Our purpose is to assess subtle structural brain changes using Voxel-based morphometry(VBM) in Korean ALS patients compared to normal brain.

METHODS We analyzed neuroimaing findings of 33 consecutive patients with motor neuron disease in our ALS clinic using 3.0 Tesla MRI and compared to 33 age-matched healthy controls. We also investigated their spatial characteristics of brain. Patients with sporadic ALS (male:15, female : 18) 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. Voxel-based analysis between ALS patients and controls were performed. And subgroup analysis between bulbar onset and limb onset in ALS patients were performed. Correlation analyses of volumetry by disease duration, disease severity and respiratory function were performed.

RESULTS: In analysis of VBM, in ALS patients there are motor & extramotor system involvement in brain compared with controls. Limb onset ALS has more predominantly motor system involvement, in contrast bulbar onset ALS has more predominantly extramotor system involvement. And K-ALSFRS score is correlated with premotor cortex atrophy. Disease duration is most important factor in brain structural changes in ALS patients. Respiratory insufficiency is correlated with parahippocampus and occipital cortex atrophic changes.

CONCLUSIONS: This was the first large scale study of Korean ALS patients in one center using high Tesla MRI. We defined that ALS is a multisystem degenerative disease by imaging study. Brain structural changes in ALS patients is affected by disease duration and respiratory insufficiency. Subgroups of ALS has different brain atrophic changes that can correlate with clinical difference.