Targeting phosphocreatine metabolism in relapsing-remitting multiple sclerosis: evaluation with brain MRI, <script type="math/tex">^{1}H</script>and <script type="math/tex">^{31}P</script> MRS, and clinical and cognitive testing

Cambron, Melissa; Reynders, Tatjana; Debruyne, Jan; Reyngoudt, Harmen; Ribbens, Annemie; Achten, Erik; Laureys, Guy

doi:10.1007/S00415-018-9039-9

Title

Targeting phosphocreatine metabolism in relapsing-remitting multiple sclerosis: evaluation with brain MRI, $^{1}H$ and $^{31}P$ MRS, and clinical and cognitive testing

Author

Cambron, Melissa

Reynders, Tatjana

Debruyne, Jan

Reyngoudt, Harmen

Ribbens, Annemie

Achten, Erik

Laureys, Guy

Abstract

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.

Language

English

Source (journal)

Journal of neurology. - Berlin, 1974, currens

Publication

Berlin : 2018

ISSN

0340-5354 [print]

1432-1459 [online]

DOI

10.1007/S00415-018-9039-9

Volume/pages