title: A comprehensive assessment of cerebellar damage in multiple sclerosis using diffusion tractography and volumetric analysis.
abstract: BACKGROUND
  White matter (WM) and grey matter (GM) brain damage in multiple sclerosis (MS) is widespread, but the extent of cerebellar involvement and impact on disability needs to be clarified.
  
  
  OBJECTIVE
  This study aimed to assess cerebellar WM and GM atrophy and the degree of fibre coherence in the main cerebellar connections, and their contribution to disability in relapsing-remitting MS (RRMS) and primary progressive MS (PPMS).
  
  
  METHODS
  Fourteen patients with RRMS, 12 patients with PPMS and 16 healthy controls were recruited. Cerebellar WM and GM volumes and tractography-derived measures from the middle and superior cerebellar peduncles, including fractional anisotropy (FA), mean diffusivity (MD), and directional diffusivities, were quantified from magnetic resonance imaging (MRI). Patients were assessed on clinical scores, including the MS Functional Composite score subtests. Linear regression models were used to compare imaging measures between 12 RRMS, 11 PPMS and 16 controls, and investigate their association with clinical scores.
  
  
  RESULTS
  Patients with PPMS showed reduced FA and increased radial diffusivity in the middle cerebellar peduncle compared with controls and patients with RRMS. In PPMS, lower cerebellar WM volume was associated with worse performance on the upper limb test. In the same patient group, we found significant relationships between superior cerebellar peduncle FA and upper limb function, and between superior cerebellar peduncle FA, MD and radial diffusivity and speed of walking.
  
  
  CONCLUSIONS
  These findings indicate reduced fibre coherence in the main cerebellar connections, and link damage in the whole cerebellar WM, and, in particular, in the superior cerebellar peduncle, to motor deficit in PPMS.
authors.affiliation: Department of Neuroinflammation, UCL Institute of Neurology, London, UK.
authors.forename: V M
authors.initials: VM
authors.lastname: Anderson
authors.forename: C A M
authors.initials: CA
authors.lastname: Wheeler-Kingshott
authors.forename: K
authors.initials: K
authors.lastname: Abdel-Aziz
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
authors.forename: A
authors.initials: A
authors.lastname: Toosy
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: O
authors.initials: O
authors.lastname: Ciccarelli
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy / Q000473:pathology; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D018737:Hand Strength / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D009412:Nerve Fibers / Q000473:pathology*