title: Grey matter correlates of clinical variables in amyotrophic lateral sclerosis (ALS): a neuroimaging study of ALS motor phenotype heterogeneity and cortical focality.
abstract: BACKGROUND
  Body region of onset and functional disability are key components of disease heterogeneity in amyotrophic lateral sclerosis (ALS).
  
  
  OBJECTIVE
  To evaluate patterns of grey matter pathology in the motor cortex and correlate focal structural changes with functional disability.
  
  
  METHODS
  We conducted a single-centre neuroimaging study of a cohort of 33 cognitively normal patients with amyotrophic lateral sclerosis (ALS) and 44 healthy controls. A voxel-wise generalised linear model was used to investigate the distribution of disease burden within the motor cortex in relation to clinical disability.
  
  
  RESULTS
  Patients with bulbar onset have bilateral focal atrophy in the bulbar segment of the motor homunculus compared with patients with limb onset who have focal cortical changes in the limb segment of their motor strip. Furthermore, the extent to which different body regions are affected in ALS corresponds to the extent of focal grey matter loss in the primary motor cortex. Cortical ALS pathology also extends beyond the motor cortex affecting frontal, occipital and temporal regions.
  
  
  CONCLUSIONS
  Focal grey matter atrophy within the motor homunculus corresponds with functional disability in ALS. The findings support the existing concepts of cortical focality and motor phenotype heterogeneity in ALS.
authors.affiliation: Trinity College Institute of Neuroscience (TCIN), Lloyd Building, Trinity College Dublin, Dublin, Ireland. bedepeter@hotmail.com
authors.forename: Peter
authors.initials: P
authors.lastname: Bede
authors.forename: Arun
authors.initials: A
authors.lastname: Bokde
authors.forename: Marwa
authors.initials: M
authors.lastname: Elamin
authors.forename: Susan
authors.initials: S
authors.lastname: Byrne
authors.forename: Russell L
authors.initials: RL
authors.lastname: McLaughlin
authors.forename: Norah
authors.initials: N
authors.lastname: Jordan
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.forename: Laura
authors.initials: L
authors.lastname: Gallagher
authors.forename: Catherine
authors.initials: C
authors.lastname: Lynch
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fagan
authors.forename: Niall
authors.initials: N
authors.lastname: Pender
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
mesh_terms: D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology* / Q000503:physiopathology; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D004522:Educational Status; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007494:Ireland; D008279:Magnetic Resonance Imaging; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology; D008875:Middle Aged; D009044:Motor Cortex / Q000473:pathology; D009068:Movement; D059906:Neuroimaging / Q000379:methods*; D009483:Neuropsychological Tests; D010641:Phenotype; D012042:Registries
keywords: ALS; MRI; Motor Neuron Disease; Neuroanatomy; Neuroradiology