Brain Imaging and Behavior

, Volume 12, Issue 2, pp 547–563 | Cite as

Gray matter and white matter changes in non-demented amyotrophic lateral sclerosis patients with or without cognitive impairment: A combined voxel-based morphometry and tract-based spatial statistics whole-brain analysis

  • Foteini Christidi
  • Efstratios Karavasilis
  • Franz Riederer
  • Ioannis Zalonis
  • Panagiotis Ferentinos
  • Georgios Velonakis
  • Sophia Xirou
  • Michalis Rentzos
  • Georgios Argiropoulos
  • Vasiliki Zouvelou
  • Thomas Zambelis
  • Athanasios Athanasakos
  • Panagiotis Toulas
  • Konstantinos Vadikolias
  • Efstathios Efstathopoulos
  • Spyros Kollias
  • Nikolaos Karandreas
  • Nikolaos Kelekis
  • Ioannis Evdokimidis
Original Research

Abstract

The phenotypic heterogeneity in amyotrophic lateral sclerosis (ALS) implies that patients show structural changes within but also beyond the motor cortex and corticospinal tract and furthermore outside the frontal lobes, even if frank dementia is not detected. The aim of the present study was to investigate both gray matter (GM) and white matter (WM) changes in non-demented amyotrophic lateral sclerosis (ALS) patients with or without cognitive impairment (ALS-motor and ALS-plus, respectively). Nineteen ALS-motor, 31 ALS-plus and 25 healthy controls (HC) underwent 3D–T1-weighted and 30-directional diffusion-weighted imaging on a 3 T MRI scanner. Voxel-based morphometry and tract-based spatial-statistics analysis were performed to examine GM volume (GMV) changes and WM differences in fractional anisotropy (FA), axial and radial diffusivity (AD, RD, respectively). Compared to HC, ALS-motor patients showed decreased GMV in frontal and cerebellar areas and increased GMV in right supplementary motor area, while ALS-plus patients showed diffuse GMV reduction in primary motor cortex bilaterally, frontotemporal areas, cerebellum and basal ganglia. ALS-motor patients had increased GMV in left precuneus compared to ALS-plus patients. We also found decreased FA and increased RD in the corticospinal tract bilaterally, the corpus callosum and extra-motor tracts in ALS-motor patients, and decreased FA and increased AD and RD in motor and several WM tracts in ALS-plus patients, compared to HC. Multimodal neuroimaging confirms motor and extra-motor GM and WM abnormalities in non-demented cognitively-impaired ALS patients (ALS-plus) and identifies early extra-motor brain pathology in ALS patients without cognitive impairment (ALS-motor).

Keywords

Amyotrophic lateral sclerosis Multimodal neuroimaging Voxel-based morphometry Tract-based spatial statistics Cognition 

Abbreviations

GM

Gray matter

WM

White matter

ALS

Amyotrophic lateral sclerosis (ALS)

HC

Healthy controls

GMV

Gray matter volume

FA

Fractional anisotropy

AD

Axial diffusivity

RD

Radial diffusivity

MND

Motor neuron disorders

CNS

Central nervous system

FTD

Frontotemporal dementia

TBSS

Tract-based spatial statistics

MRI

Magnetic resonance imaging

VBM

Voxel-based morphometry

ALSFRS-R

Revised Amyotrophic Lateral Sclerosis Functional Rating Scale

HR_3DT1w

3D–T1-weighted sequence;

DTI

Diffusion-tensor imaging

T2-FLAIR

T2-Fluid attenuation inversion recovery

SPM

Statistical Parametric Mapping

CSF

Cerebrospinal fluid

FWHM

Full-width-at-half-maximum

TIV

Total intracranial volume

FWE

Family-wise error

FMRIB

Functional Magnetic Resonance Imaging of the Brain

FSL

FMRIB Software Library

MNI

Montreal Neurological Institute

TFCE

Threshold-free cluster enhancement

ACC

Anterior cingulate cortex

SMA

Supplementary motor area

CST

Corticospinal tract

CC

Corpus callosum

UF

Uncinate fasciculus

SLF

Superior longitudinal fasciculus

IFOF

Inferior fronto-occipital fasciculus

SBM

Surface-based morphometry

fMRI

Functional magnetic resonance imaging.

Notes

Acknowledgements

F.C. is supported by the IKY FELLOWSHIPS OF EXCELLENCE FOR POSTGRADUATE STUDIES IN GREECE - SIEMENS PROGRAM (SPHA:11118/13a) and IKY SHORT TERMS PROGRAM (2013-ΠΕ2-SHORT TERMS-18671). We acknowledge Odysseas Benekos, Giannis Spandonis and the Philips Medical System for providing all necessary research keys for MRI sequence acquisition. We also acknowledge the radiologists-technologists of Research Radiology & Medical Imaging Department (Ioannis Gkerles, Christos Lioulios, Anestis Passalis, Efstathios Xenos) for conducting and facilitating participants’ MR scanning. Finally, we would like to thank patients with ALS and their families, as well as healthy volunteers for their willingness to participate to the present study.

Compliance with ethical standards

Funding

The study did not receive any funding. F.C. is supported by the IKY FELLOWSHIPS OF EXCELLENCE FOR POSTGRADUATE STUDIES IN GREECE - SIEMENS PROGRAM (SPHA:11118/13a) and IKY SHORT TERMS PROGRAM (2013-ΠΕ2-SHORT TERMS-18671).

Conflict of interest

Author F.C., Author E.K., Author F.R., Author I.Z., Author P.F., Author G.V., Author S.X., Author I.Z., Author M.R., Author G.A., Author V.Z., Author T.Z., Author A.A., Author P.T., Author K.V., Author E.E., Author S.K., Author N.K., Author N.K., Author I.E. declares that she/he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Foteini Christidi
    • 1
  • Efstratios Karavasilis
    • 2
  • Franz Riederer
    • 3
  • Ioannis Zalonis
    • 1
  • Panagiotis Ferentinos
    • 4
  • Georgios Velonakis
    • 2
  • Sophia Xirou
    • 1
  • Michalis Rentzos
    • 1
  • Georgios Argiropoulos
    • 2
  • Vasiliki Zouvelou
    • 1
  • Thomas Zambelis
    • 1
  • Athanasios Athanasakos
    • 2
  • Panagiotis Toulas
    • 2
  • Konstantinos Vadikolias
    • 5
  • Efstathios Efstathopoulos
    • 2
  • Spyros Kollias
    • 6
  • Nikolaos Karandreas
    • 1
  • Nikolaos Kelekis
    • 2
  • Ioannis Evdokimidis
    • 1
  1. 1.First Department of Neurology, Aeginition Hospital, Medical SchoolNational & Kapodistrian UniversityAthensGreece
  2. 2.Second Department of Radiology, Attikon University Hospital, Medical SchoolNational and Kapodistrian UniversityAthensGreece
  3. 3.Neurological Center Rosenhuegel and Karl Landsteiner Institute for Epilepsy Research and Cognitive NeurologyViennaAustria
  4. 4.Second Department of Psychiatry, Attikon University Hospital, Medical SchoolNational & Kapodistrian UniversityAthensGreece
  5. 5.Department of NeurologyDemokritos University of ThraceAlexandroupolisGreece
  6. 6.Clinic of NeuroradiologyUniversity Hospital ZurichZurichSwitzerland

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