title: Long-term study of brain 1H-MRS study in multiple sclerosis: effect of glatiramer acetate therapy on axonal metabolic function and feasibility of long-Term H-MRS monitoring in multiple sclerosis.
abstract: Glatiramer acetate (GA) has several putative mechanisms of action with the potential of limiting sublethal axonal injury in the central nervous system (CNS). Brain proton magnetic resonance spectroscopy ((1)H-MRS) allows in vivo examination of axonal integrity by quantifying the neuronal marker N-acetylaspartate (NAA), often expressed as a ratio to creatine (Cr). We showed that treatment with GA led to improvement in NAA/Cr over a 2-year period. We now report the results of this ongoing study after 4 years of annual brain (1)H-MRS examinations. Compared to baseline, at year 4, patients receiving continuous GA therapy showed a 12.7% increase in NAA/Cr and (P= .03) in the multivoxel brain volume of interest (VOI) studied and by 9.6% (P= .04) in the normal-appearing white matter within the VOI. Three patients in the control group who began therapy with GA during the course of the study showed similar increases in NAA/Cr after the first year of therapy. These data support the long-term effect of GA on maintaining axonal metabolic function and protection from sublethal injury as well as the feasibility of employing brain (1)H-MRS in long-term investigative studies in MS.
authors.affiliation: Multiple Sclerosis Clinical Research Center, Department of Neurology, The Detroit Medical Center, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. okhan@med.wayne.edu
authors.forename: Omar
authors.initials: O
authors.lastname: Khan
authors.forename: Yimin
authors.initials: Y
authors.lastname: Shen
authors.forename: Fen
authors.initials: F
authors.lastname: Bao
authors.forename: Christina
authors.initials: C
authors.lastname: Caon
authors.forename: Alexandros
authors.initials: A
authors.lastname: Tselis
authors.forename: Zahid
authors.initials: Z
authors.lastname: Latif
authors.forename: Imad
authors.initials: I
authors.lastname: Zak
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D003401:Creatine / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D010455:Peptides / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
chemical_list: D007166:Immunosuppressive Agents; D010455:Peptides; D001224:Aspartic Acid; D000068717:Glatiramer Acetate; C000179:N-acetylaspartate; D003401:Creatine