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March 19, 2013; 80 (12) Article

Cortical atrophy in ALS is critically associated with neuropsychiatric and cognitive changes

Eneida Mioshi, Patricia Lillo, Belinda Yew, Sharpley Hsieh, Sharon Savage, John R. Hodges, Matthew C. Kiernan, Michael Hornberger
First published February 20, 2013, DOI: https://doi.org/10.1212/WNL.0b013e31828869da
Eneida Mioshi
From Neuroscience Research Australia (E.M., P.L., B.Y., S.H., S.S., J.R.H., M.C.K., M.H.), Sydney; and the School of Medical Sciences (J.R.H., M.C.K., M.H.), University of New South Wales, Sydney, Australia.
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Patricia Lillo
From Neuroscience Research Australia (E.M., P.L., B.Y., S.H., S.S., J.R.H., M.C.K., M.H.), Sydney; and the School of Medical Sciences (J.R.H., M.C.K., M.H.), University of New South Wales, Sydney, Australia.
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Belinda Yew
From Neuroscience Research Australia (E.M., P.L., B.Y., S.H., S.S., J.R.H., M.C.K., M.H.), Sydney; and the School of Medical Sciences (J.R.H., M.C.K., M.H.), University of New South Wales, Sydney, Australia.
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Sharpley Hsieh
From Neuroscience Research Australia (E.M., P.L., B.Y., S.H., S.S., J.R.H., M.C.K., M.H.), Sydney; and the School of Medical Sciences (J.R.H., M.C.K., M.H.), University of New South Wales, Sydney, Australia.
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Sharon Savage
From Neuroscience Research Australia (E.M., P.L., B.Y., S.H., S.S., J.R.H., M.C.K., M.H.), Sydney; and the School of Medical Sciences (J.R.H., M.C.K., M.H.), University of New South Wales, Sydney, Australia.
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John R. Hodges
From Neuroscience Research Australia (E.M., P.L., B.Y., S.H., S.S., J.R.H., M.C.K., M.H.), Sydney; and the School of Medical Sciences (J.R.H., M.C.K., M.H.), University of New South Wales, Sydney, Australia.
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Matthew C. Kiernan
From Neuroscience Research Australia (E.M., P.L., B.Y., S.H., S.S., J.R.H., M.C.K., M.H.), Sydney; and the School of Medical Sciences (J.R.H., M.C.K., M.H.), University of New South Wales, Sydney, Australia.
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Michael Hornberger
From Neuroscience Research Australia (E.M., P.L., B.Y., S.H., S.S., J.R.H., M.C.K., M.H.), Sydney; and the School of Medical Sciences (J.R.H., M.C.K., M.H.), University of New South Wales, Sydney, Australia.
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Citation
Cortical atrophy in ALS is critically associated with neuropsychiatric and cognitive changes
Eneida Mioshi, Patricia Lillo, Belinda Yew, Sharpley Hsieh, Sharon Savage, John R. Hodges, Matthew C. Kiernan, Michael Hornberger
Neurology Mar 2013, 80 (12) 1117-1123; DOI: 10.1212/WNL.0b013e31828869da

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Abstract

Objective: To characterize the patterns of brain atrophy in patients with amyotrophic lateral sclerosis (ALS) with and without cognitive and neuropsychiatric symptoms, in comparison to controls and patients with ALS–frontotemporal dementia (FTD).

Methods: A total of 57 participants (ALS = 22; ALS-FTD = 17; controls = 18) were included, following current ALS and FTD criteria. Patients with ALS were further subclassified into ALS with cognitive and behavioral symptoms (ALS-plus; n = 8) and those without (ALS; n = 14). By definition, ALS-plus did not reach the diagnostic threshold for ALS-FTD. All patients underwent neuropsychological and neuropsychiatric assessments, and underwent a brain MRI. Voxel-based morphometry analysis was conducted to establish patterns of brain atrophy.

Results: Cortical atrophy in ALS was linked to neuropsychiatric and cognitive changes (ALS-plus vs ALS). Patients with ALS-plus had significant atrophy across motor and somatosensory as well as adjacent frontal and parietal areas, even after strict multiple comparison correction. By contrast, patients with ALS showed no significant cortical atrophy, and only brainstem atrophy. Importantly, atrophy in ALS-plus was not as widespread as in ALS-FTD, with ALS-plus atrophy mostly confined to motor and somatosensory areas, while atrophy in ALS-FTD also included substantial frontal and temporal atrophy.

Conclusions: The present findings establish that cortical atrophy in ALS is highly dependent upon neuropsychiatric and cognitive changes. Previous inconsistent findings of cortical atrophy in ALS likely relate to the inclusion of cognitively affected patients and patients with pure motor ALS.

GLOSSARY

ALS=
amyotrophic lateral sclerosis;
ALS-plus=
amyotrophic lateral sclerosis with cognitive and behavioral symptoms;
ALSFRS-R=
revised Amyotrophic Lateral Sclerosis Functional Rating Scale;
ANOVA=
analysis of variance;
CBI-R=
Cambridge Behavioral Inventory;
FAST=
FMRIB Automatic Segmentation Tool;
FDR=
false discovery rate;
FTD=
frontotemporal dementia;
FWE=
family-wise error;
MND=
motor neuron disease;
TFCE=
threshold-free cluster enhancement;
UMN=
upper motor neuron;
VBM=
voxel-based morphometry

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Received August 26, 2012.
  • Accepted December 11, 2012.
  • © 2013 American Academy of Neurology
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