Cerebral degeneration in amyotrophic lateral sclerosis: A prospective multicenter magnetic resonance spectroscopy study.

Journal

Neurology. Clinical practice
ISSN: 2163-0402
Titre abrégé: Neurol Clin Pract
Pays: United States
ID NLM: 101577149

Informations de publication

Date de publication:
Oct 2019
Historique:
received: 14 11 2018
accepted: 28 02 2019
entrez: 22 11 2019
pubmed: 22 11 2019
medline: 22 11 2019
Statut: ppublish

Résumé

We investigated cerebral degeneration and neurochemistry in patients with amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS). We prospectively studied 65 patients and 43 age-matched healthy controls. Participants were recruited from 4 centers as part of a study in the Canadian ALS Neuroimaging Consortium. All participants underwent single-voxel proton MRS using a protocol standardized across all sites. Metabolites reflecting neuronal integrity (total In the motor cortex, tNAA/Cr, tNAA/Cho, and tNAA/Ino ratios were reduced in the ALS group compared with controls. Group differences in tNAA/Cr and tNAA/Cho in the prefrontal cortex displayed reduced ratios in ALS patients; however, these were not statistically significant. Reduced motor cortex ratios were associated with slower foot tapping rate, whereas only motor tNAA/Ino was associated with finger tapping rate. Disease progression rate was associated with motor tNAA/Cho. Verbal fluency, semantic fluency, and digit span forwards and backwards were associated with prefrontal tNAA/Cr. This study demonstrates that cerebral degeneration in ALS is more pronounced in the motor than prefrontal cortex, that multicenter MRS studies are feasible, and that motor tNAA/Ino shows promise as a potential biomarker.

Sections du résumé

BACKGROUND BACKGROUND
We investigated cerebral degeneration and neurochemistry in patients with amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS).
METHODS METHODS
We prospectively studied 65 patients and 43 age-matched healthy controls. Participants were recruited from 4 centers as part of a study in the Canadian ALS Neuroimaging Consortium. All participants underwent single-voxel proton MRS using a protocol standardized across all sites. Metabolites reflecting neuronal integrity (total
RESULTS RESULTS
In the motor cortex, tNAA/Cr, tNAA/Cho, and tNAA/Ino ratios were reduced in the ALS group compared with controls. Group differences in tNAA/Cr and tNAA/Cho in the prefrontal cortex displayed reduced ratios in ALS patients; however, these were not statistically significant. Reduced motor cortex ratios were associated with slower foot tapping rate, whereas only motor tNAA/Ino was associated with finger tapping rate. Disease progression rate was associated with motor tNAA/Cho. Verbal fluency, semantic fluency, and digit span forwards and backwards were associated with prefrontal tNAA/Cr.
CONCLUSIONS CONCLUSIONS
This study demonstrates that cerebral degeneration in ALS is more pronounced in the motor than prefrontal cortex, that multicenter MRS studies are feasible, and that motor tNAA/Ino shows promise as a potential biomarker.

Identifiants

DOI: 10.1212/CPJ.0000000000000674 PMID: 31750025 PMC: PMC6814429
pubmed: 31750025
doi: 10.1212/CPJ.0000000000000674
pii: NEURCLINPRACT2018035204
pmc: PMC6814429
doi:

Types de publication

Journal Article

Langues

eng

Pagination

400-407

Informations de copyright

© 2019 American Academy of Neurology.

Références

Neurology. 2004 May 25;62(10):1753-7
pubmed: 15159473
J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):102-8
pubmed: 21836033
Amyotroph Lateral Scler Frontotemporal Degener. 2017 May;18(3-4):153-174
pubmed: 28054827
Ann Neurol. 2013 Jul;74(1):20-38
pubmed: 23686809
Dev Neurosci. 1993;15(3-5):289-98
pubmed: 7805581
J Neurol Sci. 2002 Jun 15;198(1-2):37-41
pubmed: 12039662
Neurology. 2012 Aug 7;79(6):583-8
pubmed: 22843269
Amyotroph Lateral Scler Other Motor Neuron Disord. 2004 Sep;5(3):141-9
pubmed: 15512902
Arch Neurol. 2001 May;58(5):729-35
pubmed: 11346367
Neurology. 1998 Jan;50(1):72-7
pubmed: 9443460
Nat Rev Neurol. 2013 Dec;9(12):708-14
pubmed: 24217521
Neurology. 2007 Apr 24;68(17):1402-10
pubmed: 17452585
J Neurol Neurosurg Psychiatry. 2006 Nov;77(11):1253-5
pubmed: 16835288
Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9
pubmed: 11464847
PLoS One. 2017 May 12;12(5):e0177680
pubmed: 28498852
AJNR Am J Neuroradiol. 2011 Feb;32(2):403-7
pubmed: 21087934
Neurology. 1998 Jun;50(6):1800-5
pubmed: 9633731
Magn Reson Med. 2001 Mar;45(3):513-6
pubmed: 11241711
Muscle Nerve. 1998 Jun;21(6):762-8
pubmed: 9585330
AJNR Am J Neuroradiol. 2011 Oct;32(9):1677-80
pubmed: 21778247
Amyotroph Lateral Scler. 2010;11(1-2):157-65
pubmed: 19242831
J Clin Neurosci. 2016 May;27:110-3
pubmed: 26765768
Eur J Radiol. 2015 Jan;84(1):151-157
pubmed: 25466774
Somatosens Mot Res. 2017 Mar;34(1):15-20
pubmed: 28114839
J Neurosci Rural Pract. 2016 Jan-Mar;7(1):102-8
pubmed: 26933355
Neuroradiology. 2010 Dec;52(12):1079-85
pubmed: 20369234
Magn Reson Med. 1993 Dec;30(6):672-9
pubmed: 8139448
Neuroradiology. 2001 Jul;43(7):537-41
pubmed: 11512581
J Magn Reson Imaging. 2010 Feb;31(2):305-8
pubmed: 20099342
AJNR Am J Neuroradiol. 2010 Nov;31(10):1799-806
pubmed: 20801763
Neurology. 1994 Oct;44(10):1933-8
pubmed: 7936250
Neurology. 1999 Nov 10;53(8):1665-70
pubmed: 10563610
Radiology. 2018 Jun;287(3):955-964
pubmed: 29361242
Amyotroph Lateral Scler. 2010 Dec;11(6):508-13
pubmed: 20698808
J Neurol. 2007 Aug;254(8):1099-106
pubmed: 17431700
Neurology. 1999 Jul 13;53(1):71-9
pubmed: 10408539

Auteurs

Ojas Srivastava (O)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Chris Hanstock (C)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Sneha Chenji (S)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Dennell Mah (D)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Dean Eurich (D)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Daniel Ta (D)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Peter Seres (P)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Collin Luk (C)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Lorne Zinman (L)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Agessandro Abrahao (A)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Simon J Graham (SJ)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Angela Genge (A)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Lawrence Korngut (L)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Richard Frayne (R)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Sanjay Kalra (S)

Faculty of Science (OS); Department of Biomedical Engineering (CH, PS, SK); Neuroscience and Mental Health Institute (SC, DT, SK); Divison of Neurology (DM, CL, SK), Department of Medicine; School of Public Health (DE); University of Alberta, Edmonton, Alberta; Sunnybrook Health Sciences Centre (LZ, AA, SJG), University of Toronto, Toronto, Ontario; Montreal Neurological Institute and Hospital (AG), McGill University, Montreal, Quebec; Departments of Radiology and Clinical Neurosciences (LK, RF), Hotchkiss Brain Institute, University of Calgary; and Seaman Family MR Research Centre (LK, RF), Foothills Medical Centre, Calgary, Alberta, Canada.

Classifications MeSH