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. 2012;7(8):e43993.
doi: 10.1371/journal.pone.0043993. Epub 2012 Aug 29.

Grey and white matter changes across the amyotrophic lateral sclerosis-frontotemporal dementia continuum

Patricia Lillo  1 , Eneida Mioshi, James R Burrell, Matthew C Kiernan, John R Hodges, Michael Hornberger
Affiliations

Grey and white matter changes across the amyotrophic lateral sclerosis-frontotemporal dementia continuum

Patricia Lillo et al. PLoS One. 2012.

Abstract

There is increasing evidence that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) lie on a clinical, pathological and genetic continuum with patients of one disease exhibiting features of the other. Nevertheless, to date, the underlying grey matter and white matter changes across the ALS-FTD disease continuum have not been explored. In this study fifty-three participants with ALS (n = 10), ALS-FTD (n = 10) and behavioural variant FTD (bvFTD; n = 15) as well as controls (n = 18), underwent detailed clinical assessment plus structural imaging using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis of magnetic resonance brain imaging to examine grey and white matter differences and commonalities across the continuum. Importantly, patient groups were matched for age, education, gender and disease duration. VBM and DTI results showed that changes in the ALS group were confined mainly to the motor cortex and anterior cingulate as well as their underlying white matter tracts. ALS-FTD and bvFTD showed widespread grey matter and white matter changes involving frontal and temporal lobes. Extensive prefrontal cortex changes emerged as a marker for bvFTD compared to other subtypes, while ALS-FTD could be distinguished from ALS by additional temporal lobe grey and white matter changes. Finally, ALS could be mainly distinguished from the other two groups by corticospinal tract degeneration. The present study shows for the first time that FTD and ALS overlap in anterior cingulate, motor cortex and related white matter tract changes across the whole continuum. Nevertheless, frontal and temporal atrophy as well as corticospinal tract degeneration emerged as marker for subtype classification, which will inform future diagnosis and target disease management across the continuum.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Unique grey matter atrophy across patient groups.
Voxel-based morphometry analysis showing regions of unique brain atrophy across groups. Clusters are overlaid on the MNI standard brain (t = 2.41). Coloured voxels show regions that were significant in the analyses for p<0.05 FWE corrected.
Figure 2
Figure 2. Overlap grey matter atrophy across patient groups.
Voxel-based morphometry analysis showing region of brain atrophy overlap; i) and ii) show sagittal and coronal views of the anterior cingulate atrophy cluster; iii) and iv) show sagittal and coronal views of the motor cortex atrophy cluster. Clusters are overlaid on the MNI standard brain (t = 2.41).
Figure 3
Figure 3. Unique white matter changes across patient groups.
Diffusion tensor imaging analysis showing regions of unique white matter changes across groups. Clusters are overlaid on the MNI standard brain (t = 2.41). Coloured voxels show regions that were significant in the analyses for p<0.05 FWE corrected.
Figure 4
Figure 4. Overlap white matter changes across patient groups.
Diffusion tensor imaging analysis showing regions of unique white matter changes across groups. Clusters are overlaid on the MNI standard brain (t = 2.41). Coloured voxels show regions that were significant in the analyses for p<0.05 FWE corrected.
Figure 5
Figure 5. Schematic summary of main findings.
Summary of main grey matter regions and their underlying white matter tracts across patient groups. Shading of text boxes indicates severity of impairment based on the imaging findings with lighter boxes indicating higher impairment and darker boxes indicated lesser impairment. CST = corticospinal tract; MPFC = medial prefrontal cortex; CC = corpus callosum; ILF = inferior longitudinal fasciculus.
See this image and copyright information in PMC

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Grants and funding

PL is supported by Comisión Nacional de Investigación Científica y Tecnológica, Government of Chile (CONICYT scholarship) and Faculty of Medicine, University of Chile; EM is supported by an NHMRC post-doctoral fellowship (1016399); JRB is supported by the NHMRC; MCK is supported by the NHMRC; JRH is supported by an Australian Research Council Federation Fellowship (FF077622); and MH is supported by an Australian Research Council Research Fellowship (DP110104202). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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