title: Longitudinal changes in cerebellar and subcortical volumes in adult-onset Niemann-Pick disease type C patients treated with miglustat.
abstract: Niemann-Pick disease type C (NPC) is a rare neurovisceral disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment available to date is miglustat, an iminosugar inhibiting the accumulation of lipid by-products in neurons. This study explored how changes in cerebellar grey and white matter volumes, and in subcortical volumes, related to patient treatment status and disability and ataxia ratings. Nine adult-onset NPC patients and 17 matched controls underwent T1-weighted MRI. One patient was not receiving miglustat, and pre-treatment data were available for a further patient. Semi-automated cerebellar and subcortical segmentation was undertaken, and the rates of change in putamen, hippocampal, thalamic and caudal volumes, and grey and white matter cerebellar volumes, were compared to rates of change in Iturriaga disability score, Brief Ataxia Rating Scale (BARS), and horizontal saccadic gain. Untreated NPC patients appeared to lose cerebellar grey and white matter, bilateral thalamic volume, and right caudate volume faster than treated patients. Cerebellar grey matter volume loss and volume loss in the left thalamus were significantly correlated with Iturriaga disability scale changes. Change in both cerebellar grey and white matter was correlated with decrease in horizontal saccadic gain, but not with change in BARS. This is the first study to examine longitudinal treatment effects of miglustat on cerebellar and subcortical volumes in patients with adult-onset NPC, and is evidence that miglustat may have a protective effect on cerebellar and subcortical structure and function.
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, Melbourne Brain Centre, University of Melbourne, Melbourne, VIC, 3052, Australia.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bowman
authors.affiliation: Royal Melbourne Hospital, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Level 2, John Cade Building, Parkville, VIC, 3050, Australia. mark.walterfang@mh.org.au.
authors.forename: Mark
authors.initials: M
authors.lastname: Walterfang
authors.affiliation: Department of Optometry and Vision Sciences, University of Melbourne, Melbourne, VIC, 3010, Australia.
authors.forename: Larry
authors.initials: L
authors.lastname: Abel
authors.affiliation: Department of Radiology, The Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Desmond
authors.affiliation: Department of Pediatrics, Monash University, Clayton, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Fahey
authors.affiliation: Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Parkville, VIC, Australia.
authors.forename: Dennis
authors.initials: D
authors.lastname: Velakoulis
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D002421:Caudate Nucleus / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology*; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy / Q000473:pathology*; D009929:Organ Size; D011699:Putamen / Q000473:pathology*; D013788:Thalamus / Q000473:pathology*; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat
keywords: Ataxia; Cerebellum; Lysosomal; Niemann–Pick type C; Saccades; Thalamus