Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy

In vivo assessment of structural changes

Antonella Castellano, Nico Papinutto, Marcello Cadioli, Gianluca Brugnara, Antonella Iadanza, Graziana Scigliuolo, Davide Pareyson, Graziella Uziel, Wolfgang Köhler, Patrick Aubourg, Andrea Falini, Roland G. Henry, Letterio S. Politi, Ettore Salsano

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 (P50.0001). A mean 16% reduction of spinal cord white matter fractional anisotropy (P40.0003) with a concomitant 9.7% axial diffusivity reduction (P50.009) and 34.5% radial diffusivity increase (P50.009) 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 (P50.001) 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, P50.01) 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.

Original languageEnglish
Pages (from-to)1735-1746
Number of pages12
JournalBrain
Volume139
Issue number6
DOIs
Publication statusPublished - 2016

Fingerprint

Adrenoleukodystrophy
Spinal Cord
Pyramidal Tracts
Diffusion Tensor Imaging
Anisotropy
Brain
Demyelinating Diseases
Magnetic Resonance Imaging
Inborn Genetic Diseases
Hereditary Spastic Paraplegia
Neuroimaging
Healthy Volunteers
Cross-Sectional Studies
Radiation
Pathology
White Matter

Keywords

  • Diffusion tensor imaging
  • TBSS
  • X-linked adrenoleukodystrophy

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Castellano, A., Papinutto, N., Cadioli, M., Brugnara, G., Iadanza, A., Scigliuolo, G., ... Salsano, E. (2016). Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy: In vivo assessment of structural changes. Brain, 139(6), 1735-1746. https://doi.org/10.1093/brain/aww068

Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy : In vivo assessment of structural changes. / Castellano, Antonella; Papinutto, Nico; Cadioli, Marcello; Brugnara, Gianluca; Iadanza, Antonella; Scigliuolo, Graziana; Pareyson, Davide; Uziel, Graziella; Köhler, Wolfgang; Aubourg, Patrick; Falini, Andrea; Henry, Roland G.; Politi, Letterio S.; Salsano, Ettore.

In: Brain, Vol. 139, No. 6, 2016, p. 1735-1746.

Research output: Contribution to journalArticle

Castellano, A, Papinutto, N, Cadioli, M, Brugnara, G, Iadanza, A, Scigliuolo, G, Pareyson, D, Uziel, G, Köhler, W, Aubourg, P, Falini, A, Henry, RG, Politi, LS & Salsano, E 2016, 'Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy: In vivo assessment of structural changes', Brain, vol. 139, no. 6, pp. 1735-1746. https://doi.org/10.1093/brain/aww068
Castellano A, Papinutto N, Cadioli M, Brugnara G, Iadanza A, Scigliuolo G et al. Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy: In vivo assessment of structural changes. Brain. 2016;139(6):1735-1746. https://doi.org/10.1093/brain/aww068
Castellano, Antonella ; Papinutto, Nico ; Cadioli, Marcello ; Brugnara, Gianluca ; Iadanza, Antonella ; Scigliuolo, Graziana ; Pareyson, Davide ; Uziel, Graziella ; Köhler, Wolfgang ; Aubourg, Patrick ; Falini, Andrea ; Henry, Roland G. ; Politi, Letterio S. ; Salsano, Ettore. / Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy : In vivo assessment of structural changes. In: Brain. 2016 ; Vol. 139, No. 6. pp. 1735-1746.
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T1 - Quantitative MRI of the spinal cord and brain in adrenomyeloneuropathy

T2 - In vivo assessment of structural changes

AU - Castellano, Antonella

AU - Papinutto, Nico

AU - Cadioli, Marcello

AU - Brugnara, Gianluca

AU - Iadanza, Antonella

AU - Scigliuolo, Graziana

AU - Pareyson, Davide

AU - Uziel, Graziella

AU - Köhler, Wolfgang

AU - Aubourg, Patrick

AU - Falini, Andrea

AU - Henry, Roland G.

AU - Politi, Letterio S.

AU - Salsano, Ettore

PY - 2016

Y1 - 2016

N2 - 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 (P50.0001). A mean 16% reduction of spinal cord white matter fractional anisotropy (P40.0003) with a concomitant 9.7% axial diffusivity reduction (P50.009) and 34.5% radial diffusivity increase (P50.009) 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 (P50.001) 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, P50.01) 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.

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KW - Diffusion tensor imaging

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