The following is a summary of “Longitudinal Metabolite Changes in Progressive Multiple Sclerosis: A Study of 3 Potential Neuroprotective Treatments,” published in the October 2023 issue of Neurology by John et al.
H-magnetic resonance spectroscopy (1H-MRS) can serve as a direct tool to evaluate medications for neuroprotection and their mechanisms in multiple sclerosis (MS). Some neurometabolites, such as tNAA, mIns, tCho, and Glx. may be linked to disability, and baseline neuroaxonal integrity has been linked to upper limb function and processing speed in secondary progressive MS (SPMS).
Researchers performed a retrospective study to evaluate the effects of 3 candidate drugs on neurometabolites and clinical disability in SPMS using 1H-MRS at 96 weeks.
The study included 108 patients with SPMS who were randomly assigned to receive neuroprotective drugs, which were amiloride [mean age 55.4 (SD 7.4), 61% female], fluoxetine [55.6 (6.6), 71%], riluzole [54.6 (6.3), 68%], or placebo [54.8 (7.9), 67%]. They utilized a 3-Tesla MRI scanner, chemical-shift imaging, 2D-point-resolved-spectroscopy (PRESS), and 3DT1.
At both baseline and the 96-week mark, measurements were taken for brain metabolites in both normal-appearing white matter (NAWM) and gray matter (GM), as well as for brain volume, lesion load, the nine-hole peg test (9HPT), and the paced auditory serial addition test. The placebo arm’s metabolite changes over 96 weeks were analyzed using paired t-tests. Metabolite differences between treatment arms and placebo and associations between baseline metabolites and upper limb function/information processing speed at 96 weeks were assessed using multiple linear regression models. A P-value < 0.05 was considered statistically significant.
In the placebo group, there was an increase in tCho in gray matter (mean difference = -0.32 IU) but a decrease in normal-appearing white matter (NAWM) (mean difference = 0.13 IU). In comparison to the placebo, the fluoxetine group had lower mIns/tCr (β = -0.21), and the riluzole group showed reductions in GM Glx (β = -0.25) and Glx/tCr (β = -0.29). Additionally, baseline tNAA (β = 0.22) and tNAA/tCr (β = 0.23) in NAWM were associated with 9HPT scores at 96 weeks.
The study demonstrated decreased membrane turnover in the placebo group over 96 weeks. Fluoxetine and riluzole altered neurometabolites associated with gliosis and glutaminergic transmission, respectively—tNAA potential marker for upper limb function.