title: Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy: in vivo assessment of structural changes.
abstract: Adrenomyeloneuropathy is the late-onset form of X-linked adrenoleukodystrophy, and is considered the most frequent metabolic hereditary spastic paraplegia. In adrenomyeloneuropathy the spinal cord is the main site of pathology. Differently from quantitative magnetic resonance imaging of the brain, little is known about the feasibility and utility of advanced neuroimaging in quantifying the spinal cord abnormalities in hereditary diseases. Moreover, little is known about the subtle pathological changes that can characterize the brain of adrenomyeloneuropathy subjects in the early stages of the disease. We performed a cross-sectional study on 13 patients with adrenomyeloneuropathy and 12 age-matched healthy control subjects who underwent quantitative magnetic resonance imaging to assess the structural changes of the upper spinal cord and brain. Total cord areas from C2-3 to T2-3 level were measured, and diffusion tensor imaging metrics, i.e. fractional anisotropy, mean, axial and radial diffusivity values were calculated in both grey and white matter of spinal cord. In the brain, grey matter regions were parcellated with Freesurfer and average volume and thickness, and mean diffusivity and fractional anisotropy from co-registered diffusion maps were calculated in each region. Brain white matter diffusion tensor imaging metrics were assessed using whole-brain tract-based spatial statistics, and tractography-based analysis on corticospinal tracts. Correlations among clinical, structural and diffusion tensor imaging measures were calculated. In patients total cord area was reduced by 26.3% to 40.2% at all tested levels (P < 0.0001). A mean 16% reduction of spinal cord white matter fractional anisotropy (P ≤ 0.0003) with a concomitant 9.7% axial diffusivity reduction (P < 0.009) and 34.5% radial diffusivity increase (P < 0.009) was observed, suggesting co-presence of axonal degeneration and demyelination. Brain tract-based spatial statistics showed a marked reduction of fractional anisotropy, increase of radial diffusivity (P < 0.001) and no axial diffusivity changes in several white matter tracts, including corticospinal tracts and optic radiations, indicating predominant demyelination. Tractography-based analysis confirmed the results within corticospinal tracts. No significant cortical volume and thickness reduction or grey matter diffusion tensor imaging values alterations were observed in patients. A correlation between radial diffusivity and disease duration along the corticospinal tracts (r = 0.806, P < 0.01) was found. In conclusion, in adrenomyeloneuropathy patients quantitative magnetic resonance imaging-derived measures identify and quantify structural changes in the upper spinal cord and brain which agree with the expected histopathology, and suggest that the disease could be primarily caused by a demyelination rather than a primitive axonal damage. The results of this study may also encourage the employment of quantitative magnetic resonance imaging in other hereditary diseases with spinal cord involvement.
authors.affiliation: 1 Neuroradiology Department, Neuroradiology Research Group and CERMAC, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy 2 Department of Neurology, University of California San Francisco, San Francisco, California, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Castellano
authors.affiliation: 2 Department of Neurology, University of California San Francisco, San Francisco, California, USA.
authors.forename: Nico
authors.initials: N
authors.lastname: Papinutto
authors.affiliation: 1 Neuroradiology Department, Neuroradiology Research Group and CERMAC, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy 3 Philips Healthcare, Monza, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Cadioli
authors.affiliation: 1 Neuroradiology Department, Neuroradiology Research Group and CERMAC, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Brugnara
authors.affiliation: 1 Neuroradiology Department, Neuroradiology Research Group and CERMAC, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Iadanza
authors.affiliation: 4 Department of Clinical Neurosciences, Fondazione IRCCS, Istituto Neurologico 'C. Besta', Milano, Italy.
authors.forename: Graziana
authors.initials: G
authors.lastname: Scigliuolo
authors.affiliation: 4 Department of Clinical Neurosciences, Fondazione IRCCS, Istituto Neurologico 'C. Besta', Milano, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Pareyson
authors.affiliation: 5 Department of Child Neurology, Fondazione IRCCS, Istituto Neurologico 'C. Besta', Milano, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Uziel
authors.affiliation: 6 Department of Neurology and Neurological Intensive Care, Fachkrankenhaus Hubertusburg, Wermsdorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Köhler
authors.affiliation: 7 Department of Paediatric Neurology, Hôpital Bicêtre, GH Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aubourg
authors.affiliation: 1 Neuroradiology Department, Neuroradiology Research Group and CERMAC, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.affiliation: 2 Department of Neurology, University of California San Francisco, San Francisco, California, USA 8 Department of Radiology and Biomedical Imaging, and Bioengineering Graduate Group, University of California San Francisco, and University of California Berkeley, California, USA.
authors.forename: Roland G
authors.initials: RG
authors.lastname: Henry
authors.affiliation: 1 Neuroradiology Department, Neuroradiology Research Group and CERMAC, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy politi.letterio@hsr.it.
authors.forename: Letterio S
authors.initials: LS
authors.lastname: Politi
authors.affiliation: 4 Department of Clinical Neurosciences, Fondazione IRCCS, Istituto Neurologico 'C. Besta', Milano, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Salsano
mesh_terms: D000326:Adrenoleukodystrophy / Q000000981:diagnostic imaging* / Q000473:pathology*; D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging / Q000379:methods / Q000706:statistics & numerical data; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008297:Male; D059906:Neuroimaging / Q000706:statistics & numerical data; D013116:Spinal Cord / Q000473:pathology*; D066127:White Matter / Q000473:pathology; D055815:Young Adult
keywords: TBSS; X-linked adrenoleukodystrophy; diffusion tensor imaging