title: Structural explanation of poor prognosis of amyotrophic lateral sclerosis in the non-demented state.
abstract: Amyotrophic lateral sclerosis (ALS), a motor neuron disease, is associated with various cortical symptoms including mild cognitive decline with behavior changes, suggesting the involvement of extra-motor areas in ALS. Our aim was to investigate the specific patterns of brain atrophy in sporadic, impaired ALS patients without commonly known genetic mutations using voxel-based morphometry.
  
  
  
  Forty-seven patients with sporadic ALS and 28 age-matched healthy controls were recruited. ALS participants were divided into three groups according to comprehensive neuropsychological testing: pure (ALS-pure), cognitive impairment (ALSci) and behavioral impairment (ALSbi). Quantitative comparison of brain atrophy patterns was performed amongst these three groups using voxel-based analysis. All analyses were adjusted for total intracranial volume, age, sex, disease duration and functional disability score.
  
  
  
  The ALSci group exhibited decreased volume in the left cerebellum, fusiform gyrus, optic radiations and corticospinal tracts compared to healthy controls. ALSci patient imaging showed decreased brain volume in the bilateral cerebellum, right putamen gray matter and bilateral superior longitudinal fasciculi white matter compared to pure ALS patients (P < 0.001 uncorrected, corrected for the entire volume). Compared to healthy controls, ALS-pure and ALSbi groups did not show any significant volume changes in gray and white matter.
  
  
  
  These findings also support the hypothesis that ALS pathogenesis has a dual focality of onset (cortex and anterior horn) with contiguous spread outwards. Additionally, neuropsychological features may be an important predictor of progression and survival rates in ALS.
authors.affiliation: Department of Neurology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: S-I
authors.initials: SI
authors.lastname: Oh
authors.affiliation: Department of Psychiatry, Center for Brain Health, NYU School of Medicine, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: de Leon
authors.affiliation: Department of Neurology, NYU School of Medicine, New York, NY, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: K-W
authors.initials: KW
authors.lastname: Oh
authors.affiliation: Department of Neurology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: J-S
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Psychiatry, Center for Brain Health, NYU School of Medicine, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Deshpande
authors.affiliation: Department of Psychiatry, Center for Brain Health, NYU School of Medicine, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Buj
authors.affiliation: Department of Neurology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging / Q000473:pathology*; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D011379:Prognosis; D011712:Pyramidal Tracts / Q000000981:diagnostic imaging / Q000473:pathology; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology
keywords: amyotrophic lateral sclerosis; atrophy; cognitive impairment; voxel-based morphometry