Please use this identifier to cite or link to this item: http://hdl.handle.net/10609/151088
Title: Longitudinal metabolite changes in progressive multiple sclerosis: a study of 3 potential neuroprotective treatments
Author: John, Nevin Alex  
Solanky, Bhavana  
De Angelis, Floriana  
Parker, Richard  
Weir, Christopher J.
Stutters, Jonathan  
Prados Carrasco, Ferran  
Schneider, Torben  
Doshi, Anisha  
Calvi, Alberto  
Williams, Thomas
Plantone, Domenico  
Monteverdi, Anita  
MacManus, Dervla  
Marshall, Ian
Barkhof, Frederik  
Gandini Wheeler-Kingshott, Claudia A.M.  
Chataway, Simon Jeremy  
MS-SMART Investigators
Citation: John, N.A. [Nevin A.], Solanky, B.S. [Bhavana S.], De Angelis, F. [Floriana], Parker, R.A. [Richard A.], Weir, C.J. [Christopher J.], Stutters, J. [Jonathan ], ... & Chataway, J. [Jeremy]. (2024). Longitudinal metabolite changes in progressive multiple sclerosis: a study of 3 potential neuroprotective treatments. Journal of Magnetic Resonance Imaging, 59(6), 2192-201. doi: 10.1002/jmri.29017
Abstract: Background. 1H-magnetic resonance spectroscopy (1H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS). Purpose. To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by 1H-MRS and their association with clinical disability in SPMS. Study-Type. Longitudinal. Population. 108 participants with SPMS randomized to receive neuroprotective drugs 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%]. Field Strength/Sequence. 3-Tesla. Chemical-shift-imaging 2D-point-resolved-spectroscopy (PRESS), 3DT1. Assessment. Brain metabolites in normal appearing white matter (NAWM) and gray matter (GM), brain volume, lesion load, nine-hole peg test (9HPT), and paced auditory serial addition test were measured at baseline and at 96-weeks. Statistical Tests. Paired t-test was used to analyze metabolite changes in the placebo arm over 96-weeks. Metabolite differences between treatment arms and placebo; and associations between baseline metabolites and upper limb function/information processing speed at 96-weeks assessed using multiple linear regression models. P-value<0.05 was considered statistically significant. Results. In the placebo arm, tCho increased in GM (mean difference = −0.32 IU) but decreased in NAWM (mean difference = 0.13 IU). Compared to placebo, in the fluoxetine arm, mIns/tCr was lower (β = −0.21); in the riluzole arm, GM Glx (β = −0.25) and Glx/tCr (β = −0.29) were reduced. Baseline tNAA(β = 0.22) and tNAA/tCr (β = 0.23) in NAWM were associated with 9HPT scores at 96-weeks. Data Conclusion. 1H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function.
Keywords: multiple sclerosis
secondary progressive multiple sclerosis
magnetic resonance spectroscopy
imaging biomarker
DOI: https://doi.org/10.1002/jmri.29017
Document type: info:eu-repo/semantics/article
Version: info:eu-repo/semantics/publishedVersion
Issue Date: 9-May-2024
Publication license: http://creativecommons.org/licenses/by/3.0/es/  
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