Progressive Neurochemical Abnormalities in Cognitive and Motor Subgroups of Amyotrophic Lateral Sclerosis: A Prospective Multicenter Study.


Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
24 08 2021
Historique:
received: 13 01 2021
accepted: 19 05 2021
entrez: 24 8 2021
pubmed: 25 8 2021
medline: 4 9 2021
Statut: ppublish

Résumé

To evaluate progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) by assessing alterations in Seventy-six patients with ALS and 59 healthy controls were enrolled in a prospective, longitudinal, multicenter study in the Canadian ALS Neuroimaging Consortium. Participants underwent serial clinical evaluations and magnetic resonance spectroscopy at baseline and 4 and 8 months using a harmonized protocol across 5 centers. NAA ratios were quantified in the motor cortex and prefrontal cortex. Patients were stratified into subgroups based on disease progression rate, upper motor neuron (UMN) signs, and cognitive status. Linear mixed models were used for baseline and longitudinal comparisons of NAA metabolite ratios. Patients with ALS had reduced NAA ratios in the motor cortex at baseline ( Progressive degeneration of the motor cortex in ALS is associated with more aggressive clinical presentations. These findings provide biological evidence of variable spatial and temporal cerebral degeneration linked to the disease heterogeneity of ALS. The use of standardized imaging protocols may have a role in clinical trials for patient selection or subgrouping. This study provides Class II evidence that MRS NAA metabolite ratios of the motor cortex are associated with more rapid disease progression and greater UMN signs in patients with ALS. ClinicalTrials.gov Identifier: NCT02405182.

Identifiants

pubmed: 34426551
pii: WNL.0000000000012367
doi: 10.1212/WNL.0000000000012367
pmc: PMC8397589
doi:

Substances chimiques

Aspartic Acid 30KYC7MIAI
N-acetylaspartate 997-55-7

Banques de données

ClinicalTrials.gov
['NCT02405182']

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e803-e813

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

© 2021 American Academy of Neurology.

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Auteurs

Daniel Ta (D)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada. sanjay.kalra@ualberta.ca.

Abdullah Ishaque (A)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Ojas Srivastava (O)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Chris Hanstock (C)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Peter Seres (P)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Dean T Eurich (DT)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Collin Luk (C)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Hannah Briemberg (H)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Richard Frayne (R)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Angela L Genge (AL)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Simon J Graham (SJ)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Lawrence Korngut (L)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Lorne Zinman (L)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada.

Sanjay Kalra (S)

From the Neuroscience and Mental Health Institute (D.T., A.I., O.S., S.K.), Department of Biomedical Engineering (C.H., P.S.), School of Public Health (D.T.E.), and Division of Neurology (C.L., S.K.), University of Alberta, Edmonton; Division of Neurology (H.B.), University of British Columbia, Vancouver; Seaman Family MR Centre (R.F.) and Hotchkiss Brain Institute (R.F., L.K.), University of Calgary, Alberta; Montreal Neurological Institute (A.L.G.), McGill University, Quebec; and Sunnybrook Health Sciences Centre (S.J.G., L.Z.), University of Toronto, Ontario, Canada. sanjay.kalra@ualberta.ca.

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