title: Upper and extra-motoneuron involvement in early motoneuron disease: a diffusion tensor imaging study.
abstract: Motoneuron disease is a term encompassing three phenotypes defined largely by the balance of upper versus lower motoneuron involvement, namely amyotrophic lateral sclerosis, primary lateral sclerosis and progressive muscular atrophy. However, neuroradiological and pathological findings in these phenotypes suggest that degeneration may exceed the neuronal system upon which clinical diagnosis is based. To further delineate the phenotypes within the motoneuron disease spectrum, this controlled study assessed the upper- and extra-motoneuron white matter involvement in cohorts of patients with motoneuron disease phenotypes shortly after diagnosis by comparing diffusion tensor imaging data of the different cohorts to those of healthy controls and directly between the motoneuron disease phenotypes (n = 12 for each cohort). Furthermore, we acquired follow-up data 6 months later to evaluate fractional anisotropy changes over time. Combined use of diffusion tensor tractography of the corticospinal tract and whole-brain voxel-based analysis allowed for comparison of the sensitivity of these techniques to detect white matter involvement in motoneuron disease. The voxel-based analysis demonstrated varying extents of white matter involvement in different phenotypes of motoneuron disease, albeit in quite similar anatomical locations. In general, fractional anisotropy reductions were modest in progressive muscular atrophy and most extensive in primary lateral sclerosis. The most extensive patterns of fractional anisotropy reduction were observed over time in the voxel-based analysis, indicating progressive extra-motor white matter degeneration in limb- and bulbar onset amyotrophic lateral sclerosis and in progressive muscular atrophy. The observation of both upper motor and extra-motoneuron involvement in all phenotypes of motoneuron disease shortly after diagnosis suggests that these are all part of a single spectrum of multisystem neurodegenerative disease. Voxel-based analysis was more sensitive to detect longitudinal changes than diffusion tensor tractography of the corticospinal tract. Voxel-based analyses may be particularly valuable in the evaluation of motor and extra-motor white matter involvement in the early symptomatic stages of motoneuron disease, and for monitoring the spread of pathology over time.
authors.affiliation: Academic Medical Centre, Department of Neurology (room H2-234), PO Box 22660, 1100 DD Amsterdam, The Netherlands. m.m.vandergraaff@amc.uva.nl
authors.forename: Maaike M
authors.initials: MM
authors.lastname: van der Graaff
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sage
authors.forename: Matthan W A
authors.initials: MW
authors.lastname: Caan
authors.forename: Erik M
authors.initials: EM
authors.lastname: Akkerman
authors.forename: Cristina
authors.initials: C
authors.lastname: Lavini
authors.forename: Charles B
authors.initials: CB
authors.lastname: Majoie
authors.forename: Aart J
authors.initials: AJ
authors.lastname: Nederveen
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Frans
authors.initials: F
authors.lastname: Vos
authors.forename: Frans
authors.initials: F
authors.lastname: Brugman
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: Maarten C
authors.initials: MC
authors.lastname: de Rijk
authors.forename: Pieter A
authors.initials: PA
authors.lastname: van Doorn
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hecke
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Peeters
authors.forename: Wim
authors.initials: W
authors.lastname: Robberecht
authors.forename: Stefan
authors.initials: S
authors.lastname: Sunaert
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
mesh_terms: D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016472:Motor Neuron Disease / Q000473:pathology*; D009046:Motor Neurons / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011712:Pyramidal Tracts / Q000473:pathology*; D012720:Severity of Illness Index