Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis

M.-Ê. Paquin; M.M. El Mendili; C. Gros; S.M. Dupont; J. Cohen-Adad; P.-F. Pradat

doi:10.3174/ajnr.A5427

Abstract

BACKGROUND AND PURPOSE: There is an emerging need for biomarkers to better categorize clinical phenotypes and predict progression in amyotrophic lateral sclerosis. This study aimed to quantify cervical spinal gray matter atrophy in amyotrophic lateral sclerosis and investigate its association with clinical disability at baseline and after 1 year.

MATERIALS AND METHODS: Twenty-nine patients with amyotrophic lateral sclerosis and 22 healthy controls were scanned with 3T MR imaging. Standard functional scale was recorded at the time of MR imaging and after 1 year. MR imaging data were processed automatically to measure the spinal cord, gray matter, and white matter cross-sectional areas. A statistical analysis assessed the difference in cross-sectional areas between patients with amyotrophic lateral sclerosis and controls, correlations between spinal cord and gray matter atrophy to clinical disability at baseline and at 1 year, and prediction of clinical disability at 1 year.

RESULTS: Gray matter atrophy was more sensitive to discriminate patients with amyotrophic lateral sclerosis from controls (P = .004) compared with spinal cord atrophy (P = .02). Gray matter and spinal cord cross-sectional areas showed good correlations with clinical scores at baseline (R = 0.56 for gray matter and R = 0.55 for spinal cord; P < .01). Prediction at 1 year with clinical scores (R² = 0.54) was improved when including a combination of gray matter and white matter cross-sectional areas (R² = 0.74).

CONCLUSIONS: Although improvements over spinal cord cross-sectional areas were modest, this study suggests the potential use of gray matter cross-sectional areas as an MR imaging structural biomarker to monitor the evolution of amyotrophic lateral sclerosis.

ABBREVIATIONS:

ALS: amyotrophic lateral sclerosis
ALSFRS-R: arm-revised ALS Functional Rating Scale
CSA: cross-sectional area
GMCSA: gray matter cross-sectional area
SC: spinal cord
SCCSA: spinal cord cross-sectional area

Footnotes

Disclosures: Marie-Êve Paquin—RELATED: Grant: Canada Research Chair in Quantitative Magnetic Resonance Imaging (JCA), Canadian Institute of Health Research (CIHR FDN-143263), Canada Foundation for Innovation (32454), Fonds de Recherche du Québec – Santé (28826), Fonds de Recherche du Québec – Nature et Technologies (2015-PR-182754), Natural Sciences and Engineering Research Council of Canada (435897-2013), Quebec BioImaging Network*. Mohamed M. El Mendili—RELATED: Grant: Association Française contre les Myopathies-Téléthon (AFM-Téléthon), Institut pour la Recherche sur la Moelle épinière et l'Encéphale (IRME), program “Investissements d'Avenir” ANR-10-IAIHU-06, Comments: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript*. Charley Gros—RELATED: Grant: Canada Research Chair in Quantitative Magnetic Resonance Imaging (JCA), Canadian Institute of Health Research (CIHR FDN-143263), Canada Foundation for Innovation (32454), Fonds de Recherche du Québec – Santé (28826), Fonds de Recherche du Québec – Nature et Technologies (2015-PR-182754), Natural Sciences and Engineering Research Council of Canada (435897-2013), Quebec BioImaging Network*. Sara Dupont—RELATED: Grant: Canada Research Chair in Quantitative Magnetic Resonance Imaging (JCA), Canadian Institute of Health Research, (CIHR FDN-143263), Canada Foundation for Innovation (32454), Fonds de Recherche du Québec – Santé (28826), Fonds de Recherche du Québec – Nature et Technologies (2015-PR-182754), Natural Sciences and Engineering Research Council of Canada (435897-2013), Quebec BioImaging Network*. Julien Cohen-Adad—RELATED: Grant: Canadian Institutes of Health Research*. *Money paid to the institution.
This work was supported by the Canada Research Chair in Quantitative Magnetic Resonance Imaging (J.C.-A.), the Canadian Institute of Health Research (CIHR FDN-143263), the Canada Foundation for Innovation (32454), the Fonds de Recherche du Québec - Santé (28826), the Fonds de Recherche du Québec – Nature et Technologies (2015-PR-182754), the Natural Sciences and Engineering Research Council of Canada (435897-2013), the Quebec BioImaging Network and the Association Française contre les Myopathies, the Institut pour la Recherche sur la Moelle épinière et l'Encéphale, and the “Investissements d'avenir” (ANR-10-IAIHU-06).