title: The impact of isolated lesions on white-matter fiber tracts in multiple sclerosis patients.
abstract: Infratentorial lesions have been assigned an equivalent weighting to supratentorial plaques in the new McDonald criteria for diagnosing multiple sclerosis. Moreover, their presence has been shown to have prognostic value for disability. However, their spatial distribution and impact on network damage is not well understood. As a preliminary step in this study, we mapped the overall infratentorial lesion pattern in relapsing-remitting multiple sclerosis patients (N = 317) using MRI, finding the pons (lesion density, 14.25/cm(3)) and peduncles (13.38/cm(3)) to be predilection sites for infratentorial lesions. Based on these results, 118 fiber bundles from 15 healthy controls and a subgroup of 23 patients showing lesions unilaterally at the predilection sites were compared using diffusion tensor imaging to analyze the impact of an isolated infratentorial lesion on the affected fiber tracts. Fractional anisotropy, mean diffusion as well as axial and radial diffusivity were investigated at the lesion site and along the entire fiber tract. Infratentorial lesions were found to have an impact on the fractional anisotropy and radial diffusivity not only at the lesion site itself but also along the entire affected fiber tract. As previously found in animal experiments, inflammatory attack in the posterior fossa in multiple sclerosis impacts the whole affected fiber tract. Here, this damaging effect, reflected by changes in diffusivity measures, was detected in vivo in multiple sclerosis patients in early stages of the disease, thus demonstrating the influence of a focal immune attack on more distant networks, and emphasizing the pathophysiological role of Wallerian degeneration in multiple sclerosis.
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany ; Neuroimage Center (NIC) of the Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University, Mainz, Germany.
authors.forename: Amgad
authors.initials: A
authors.lastname: Droby
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany ; Neuroimage Center (NIC) of the Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University, Mainz, Germany.
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Fleischer
authors.affiliation: Department of Computer Science, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Carnini
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany ; Neuroimage Center (NIC) of the Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University, Mainz, Germany.
authors.forename: Hilga
authors.initials: H
authors.lastname: Zimmermann
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Siffrin
authors.affiliation: Department of Neuroradiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Gawehn
authors.affiliation: Department of Biomedical Magnetic Resonance, University Hospital, Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Erb
authors.affiliation: Department of Computer Science, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hildebrandt
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany ; Neuroimage Center (NIC) of the Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University, Mainz, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Baier
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany ; Neuroimage Center (NIC) of the Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University, Mainz, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
mesh_terms: D000328:Adult; D001933:Brain Stem / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology*; D009412:Nerve Fibers / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
keywords: AD, axial diffusivity; Brainstem; Diffusion tensor imaging; EAE, experimental autoimmune encephalomyelitis; FA, fractional anisotropy; Fractional anisotropy; ICP, inferior cerebellar peduncle; LD, lesion density; LSAF, left superior arcuate fasciculus; MD, mean diffusivity; Multiple sclerosis; NAWM, normal-appearing white matter; RD, radial diffusivity; White matter