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Targeting phosphocreatine metabolism in relapsing-remitting multiple sclerosis: evaluation with brain MRI, and MRS, and clinical and cognitive testing
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| Background/objectives Fluoxetine and prucalopride might change phosphocreatine (PCr) levels via the cAMP-PKA pathway, an interesting target in the neurodegenerative mechanisms of MS. Methods We conducted a two-center double-blind, placebo-controlled, randomized trial including 48 relapsing-remitting MS patients. Patients were randomized to receive placebo (n = 13), fluoxetine (n = 15), or prucalopride (n = 14) for 6 weeks. Proton (H-1) and phosphorus (P-31) magnetic resonance spectroscopy (MRS) as well as volumetric and perfusion MR imaging were performed at weeks 0, 2, and 6. Clinical and cognitive testing were evaluated at weeks 0 and 6. Results No significant changes were observed for both P-31 and H-1 MRS indices. We found a significant effect on white matter volume and a trend towards an increase in grey matter and whole brain volume in the fluoxetine group at week 2; however, these effects were not sustained at week 6 for white matter and whole brain volume. Fluoxetine and prucalopride showed a positive effect on 9-HPT, depression, and fatigue scores. Conclusion Both fluoxetine and prucalopride had a symptomatic effect on upper limb function, fatigue, and depression, but this should be interpreted with caution. No effect of treatment was found on P-31 and H-1 MRS parameters, suggesting that these molecules do not influence the PCr metabolism. |
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English
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Journal of neurology. - Berlin | |
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Berlin : 2018
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0340-5354
0012-1037
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265:11(2018), p. 2614-2624
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000448450200013
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30187159
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