title: Relationship between Clinical Parameters and Brain Structure in Sporadic Amyotrophic Lateral Sclerosis Patients According to Onset Type: A Voxel-Based Morphometric Study.
abstract: OBJECTIVE
  Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, phenotypically heterogeneous neurodegenerative disease affecting mainly the motor neuron system. The present voxel-based morphometry (VBM) study investigated whether patterns of brain atrophy differ among sporadic ALS subtypes.
  
  
  METHODS
  Sporadic ALS patients (n = 62) with normal cognition and age-matched healthy controls (n = 57) were included in the study. ALS patients were divided into limb- and bulbar-onset groups according to clinical manifestations at symptom onset (n = 48 and 14, respectively). Clinical measures were ALS Functional Rating Scale-Revised (ALSFRS-R) score, disease duration, and forced vital capacity (FVC). Patterns of brain atrophy between ALS subgroups were compared by VBM.
  
  
  RESULTS
  In limb-onset ALS patients, atrophy was largely confined to the motor cortex and adjacent pre- and postcentral regions. However, in the bulbar-onset group, affected regions were more widespread and included these same areas but also extended to the bilateral frontotemporal and left superior temporal and supramarginal gyri, and multiple regression analysis revealed that their ALSFRS-R scores were associated with extensive loss of gray matter while FVC was related to atrophy in subcortical regions of the left superior temporal gyrus. In limb-onset ALS patients, disease duration was related to the degree of atrophy in the motor and adjacent areas.
  
  
  CONCLUSIONS
  Sporadic ALS subtypes show different patterns of brain atrophy. Neural networks related to limb and bulbar motor functions in each ALS subtype may underlie their distinct patterns of cerebral atrophy. That is, more extensive cortical and subcortical atrophy is correlated with greater ALSFRS-R severity and shorter disease duration in the bulbar-onset subtype and may explain the poor prognosis of these patients.
authors.affiliation: Department of Neurology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Hee-Jin
authors.identifier: http://orcid.org/0000-0001-7880-690X
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Center for Brain Health, Department of Psychiatry, NYU School of Medicine, New York, New York, United States of America.
authors.forename: Mony
authors.initials: M
authors.lastname: de Leon
authors.affiliation: Department of Neurology, NYU School of Medicine, New York, New York, United States of America.
authors.forename: Xiuyuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Radiology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: College of Nursing, Sungshin University, Seoul, Korea.
authors.forename: Yeon-Ha
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Neurology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged