¹H‐³¹P magnetic resonance spectroscopy: effect of biotin in multiple sclerosis

Abstract

Biotin is thought to improve functional impairment in progressive multiple sclerosis (MS) by upregulating bioenergetic metabolism. We enrolled 19 patients suffering from progressive MS (5 primary and 14 secondary Progressive‐MS). Using cerebral multinuclear magnetic resonance spectroscopy (MMRS) and clinical evaluation before and after 6 months of biotin cure, we showed significant modifications of: PME/PDE, ATP, and lactate resonances; an improvement of EDSS Neuroscore. Our results are consistent with metabolic pathways concerned with biotin action and could suggest the usefulness of MMRS for monitoring.

In Vivo Proton Exchange Rate (kex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients

“…A previous study using DS‐removed omega plots has shown that exchange rate maps can linearly reflect the pH changes in the physiological range (pH 6.2 to 7.4) 21 . PH in MS lesions in vivo with the established 31 P‐MR spectroscopy has been consistently reported at neutral to slightly alkaline (7.03 ± 0.02) 28 . Based on our research with protein phantoms at different pH, 0.03 unit of pH will lead to k ex change of only 4 s –1 which is <1% 22 .…”

Current Methods of Magnetic Resonance for Noninvasive Assessment of Molecular Aspects of Pathoetiology in Multiple Sclerosis

“…Both PME and PDE (slightly PDE > PME) peaks are detectable physiologically in WM and in GM (and are generally higher in WM) [ 140 , 141 ], with a gradual increase in PDE and a reduction in PME during aging, probably reflecting the cell membrane condition [ 142 , 143 , 144 ]. In the acute MS lesions of CDMS, PPMS, and SPMS patients, increased PDE concentrations (mainly attributable to the glycerophosphocholine) have been found [ 145 , 146 ], confirming higher myelin phospholipid degradation. Discrepancies have been perceived in the NAWM of MS patients, showing not only increased PDE levels in CDMS patients [ 147 ], but also decreased levels in SPMS and RRMS patients [ 137 , 148 ], supporting the hypothesis of the impact of lesion localization and of neuro-axonal tracking failure in MS patients.…”

“…Astrocytes actively participate in MS progression by means of their ability to inhibit remyelination and axonal regeneration not only by forming a glial scar, but also by supporting MS lesion formation via the production of cytotoxic factors and by contributing to mitochondrial dysfunction [ 98 , 99 , 137 ]. Therefore, an increased PME/PDE ratio is thought to provide an early indication of both demyelination and remyelination in MS patients [ 140 , 146 ].…”

“…Finally, the β-ATP level and PCr/β-ATP ratio have been suggested as candidates for biomarkers in the assessment of MS disease severity [ 116 , 137 , 156 ]. The indicated putative mitochondrial disorders in MS manifestation indicate that a therapeutic approach focusing on mitochondria impairment (e.g., biotin, prucalopride, fluoxetine) will probably play an important role in MS treatment; however, their effects are still under consideration [ 73 , 94 , 146 ].…”

“…A relatively stable intracellular pH in brain tissue is important because its change can affect several cellular processes (i.e., cellular enzyme activity, ion channel/transporter efficiency) and thus have an impact on many cell functions (e.g., neuronal activity, synaptic transmissions, mitochondrial functions, pathway regulation) ultimately leading to cell life or death [ 135 , 155 , 159 ]. In acute MS, lesions have been found with unchanged or slightly alkaline [ 145 , 146 , 148 ] intracellular pH values compared with healthy brain tissue, suggesting the occurrence of various metabolic processes in the observed brain tissue.…”