title: Brain structure in asymptomatic FMR1 premutation carriers at risk for fragile X-associated tremor/ataxia syndrome.
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS.
authors.affiliation: Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Battistella
authors.forename: Julien
authors.initials: J
authors.lastname: Niederhauser
authors.forename: Eleonora
authors.initials: E
authors.lastname: Fornari
authors.forename: Loyse
authors.initials: L
authors.lastname: Hippolyte
authors.forename: Aline
authors.initials: A
authors.lastname: Gronchi Perrin
authors.forename: Gaetan
authors.initials: G
authors.lastname: Lesca
authors.forename: Francesca
authors.initials: F
authors.lastname: Forzano
authors.forename: Patric
authors.initials: P
authors.lastname: Hagmann
authors.forename: Francois J G
authors.initials: FJ
authors.lastname: Vingerhoets
authors.forename: Bogdan
authors.initials: B
authors.lastname: Draganski
authors.forename: Philippe
authors.initials: P
authors.lastname: Maeder
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jacquemont
mesh_terms: D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases; D001259:Ataxia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016037:Single-Blind Method; D014202:Tremor / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human