title: Relationship between damage to the cerebellar peduncles and clinical disability in multiple sclerosis.
abstract: OBJECTIVE
  To assess whether a structural disconnection between the cerebellum and the cerebral hemispheres contributes to cerebellar and brainstem symptoms in multiple sclerosis (MS).
  
  
  METHODS
  This study was approved by the local ethics committee, and written informed consent was obtained from each participant. Brain T2 lesion load, cerebellar white matter and gray matter volumes, and tract-specific measures of the middle and superior cerebellar peduncles were derived from 172 patients with MS and 46 control subjects. Predictors of clinical impairment, which was determined at ambulation and with cerebellar and brainstem functional system scores, were identified by using random forest analysis.
  
  
  RESULTS
  Of the 172 patients, 112 (65%) had middle cerebellar peduncle T2 lesions and 74 (43%) had superior cerebellar peduncle T2 lesions. T2 lesions in the middle and superior cerebellar peduncles were more common in clinically impaired patients than in unimpaired patients (P = .05 to <.0001). Most conventional magnetic resonance imaging metrics were more abnormal in impaired patients than in unimpaired patients (P = .03 to <.0001). Except for axial diffusivity, diffusivity abnormalities of the middle and superior cerebellar peduncles were more severe in clinically impaired patients than in unimpaired patients (P = .04 to <.0001). A minimal overlap was found between diffusivity abnormalities and T2 lesions. Compared with volumetric measures of T2 lesions or cerebellar atrophy, diffusivity measures of middle or superior cerebellar peduncle damage enabled better differentiation between clinically impaired and unimpaired patients (C statistics: 61%-70%).
  
  
  CONCLUSIONS
  The assessment of middle and superior cerebellar peduncle damage contributes to the explanation of cerebellar and/or brainstem symptoms and ambulatory impairment in MS.
authors.affiliation: From the Neuroimaging Research Unit (P.P., M.A.R., E.P., M.F.) and Department of Neurology (P.P., M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Clinics of Neurology (S.M., J. Drulovic, J. Dackovic) and Radiology (T.S.O.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy (M.C.); and Department of Neurology, Scientific Institute Fondazione Don Gnocchi, Milan, Italy (D.C.).
authors.forename: Paolo
authors.initials: P
authors.lastname: Preziosa
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.forename: Sarlota
authors.initials: S
authors.lastname: Mesaros
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pagani
authors.forename: Jelena
authors.initials: J
authors.lastname: Drulovic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stosic-Opincal
authors.forename: Jelena
authors.initials: J
authors.lastname: Dackovic
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000368:Aged; D016880:Anisotropy; D016022:Case-Control Studies; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D011446:Prospective Studies; D055771:Serbia; D055815:Young Adult