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.

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.