Phosphorus magnetic resonance spectroscopy and fatigue in multiple sclerosis

Kauv, Paul; Chalah, Moussa A.; Créange, Alain; Lefaucheur, Jean‐Pascal; Ayache, Samar S.; Hodel, Jérôme

doi:10.1007/s00702-020-02221-y

Cited by 4 publications

(2 citation statements)

References 45 publications

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“…Although the occurrence of an autoimmune process is surprising at this age [ 40 – 42 ], the relapse that occurred more than one year after drug discontinuation precludes any direct relationship with the treatment. Moreover, in a previous study of hdPB in MS, no central nervous system inflammatory event was observed [ 9 , 12 , 43 ]. Thus, in this study, no new adverse events of hdPB treatment were observed, apart from those already known and reported [ 7 ].…”

Section: Discussionmentioning

confidence: 97%

High-dose pharmaceutical-grade biotin in patients with demyelinating neuropathies: a phase 2b open label, uncontrolled, pilot study

Créange,

Hutin,

Sedel

et al. 2023

BMC Neurol

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Background We proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept. Methods Phase IIb open label, uncontrolled, single center, pilot study in 15 patients (three groups of five patients) with chronic demyelinating peripheral neuropathy, i.e. chronic inflammatory demyelinating polyradiculoneuropathy, anti-myelin-associated glycoprotein neuropathy and Charcot-Marie-Tooth 1a or 1b. The investigational product was high-dose pharmaceutical-grade biotin (100 mg taken orally three times a day over a maximum of 52 weeks. The primary endpoint was a 10% relative improvement in 2 of the following 4 electrophysiological variables: motor nerve conduction velocity, distal motor latency, F wave latency, duration of the compound muscle action potential. The secondary endpoints included Overall Neuropathy Limitations Scale (ONLS) score, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score, 10-m walk test, 6-min walk test, posturography parameters, and nerve excitability variables. Results The primary endpoint was reached in one patient. In the full population analysis, some secondary endpoints parameters improved: MRC score, INCAT sensory sum score, 6-min walk distance, strength-duration time constant, and rheobase. There was a positive correlation between the improvement in the 6-min walk distance and the strength-duration time constant. Regarding the safety results, 42 adverse events occurred, of which three were of severe intensity but none was considered as related to the investigational product. Conclusions Even if the primary endpoint was not met, administration of high-dose pharmaceutical-grade biotin led to an improvement in various sensory and motor parameters, gait abilities, and nerve excitability parameters. The tolerance of the treatment was satisfactory. Trial registration ClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05.

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Section: Discussionmentioning

confidence: 97%

High-dose pharmaceutical-grade biotin in patients with demyelinating neuropathies: a phase 2b open label, uncontrolled, pilot study

Créange,

Hutin,

Sedel

et al. 2023

BMC Neurol

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“…In addition, our findings are based on single time point and it would be of interest to see if the metabolic changes are altered over time or if changes in the severity of fatigue are associated with a change in the metabolic profile. Also, our results are presented as metabolic ratios to creatine since the use of creatine as a stable metabolite is controversial, and some studies report changes in creatine levels in MS 52 . Besides, relative to the whole brain, our voxel size is small (27 cm 3 ) and limited to PCC, a structure that is composed of an almost equal amount of both white and gray matter.…”

Section: Discussionmentioning

confidence: 99%

Biochemical Correlations with Fatigue in Multiple Sclerosis Detected by MR 2D Localized Correlated Spectroscopy

Arm

Al‐iedani

Ribbons

et al. 2021

Journal of Neuroimaging

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BACKGROUND AND PURPOSE Fatigue is the common symptom in patients with multiple sclerosis (MS), yet its pathophysiological mechanism is poorly understood. We investigated the metabolic changes in fatigue in a group of relapsing‐remitting MS (RRMS) patients using MR two‐dimensional localized correlated spectroscopy (2D L‐COSY). METHODS Sixteen RRMS and 16 healthy controls were included in the study. Fatigue impact was assessed with the Modified Fatigue Impact Scale (MFIS). MR 2D L‐COSY data were collected from the posterior cingulate cortex. Nonparametric statistical analysis was used to calculate the changes in creatine scaled metabolic ratios and their correlations with fatigue scores. RESULTS Compared to healthy controls, the RRMS group showed significantly higher fatigue and lower metabolic ratios for tyrosine, glutathione, homocarnosine (GSH+Hca), fucose‐3, glutamine+glutamate (Glx), glycerophosphocholine (GPC), total choline, and N‐acetylaspartate (NAA‐2), while increased levels for isoleucine and glucose (P ≤ .05). Only GPC showed positive correlation with all fatigue domains (r = .537, P ≤ .05). On the other hand, Glx‐upper, NAA‐2, GSH+Hca, and fucose‐3 showed negative correlations with all fatigue domains (r = –.345 to –.580, P ≤ .05). While tyrosine showed positive correlation with MFIS (r = .499, P ≤ .05), cognitive fatigue was negatively correlated with total GSH (r = –.530, P ≤ .05). No correlations were found between lesion load or brain volumes with fatigue score. CONCLUSIONS Our results suggest that fatigue in MS is strongly correlated with an imbalance in neurometabolites but not structural brain measurements.

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Magnetic resonance spectroscopy and myelin water fraction in multiple sclerosis

Laule,

Vavasour

2025

Handbook of Imaging in Multiple Sclerosis

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Phosphorus magnetic resonance spectroscopy and fatigue in multiple sclerosis

Cited by 4 publications

References 45 publications

High-dose pharmaceutical-grade biotin in patients with demyelinating neuropathies: a phase 2b open label, uncontrolled, pilot study

High-dose pharmaceutical-grade biotin in patients with demyelinating neuropathies: a phase 2b open label, uncontrolled, pilot study

Biochemical Correlations with Fatigue in Multiple Sclerosis Detected by MR 2D Localized Correlated Spectroscopy

Magnetic resonance spectroscopy and myelin water fraction in multiple sclerosis

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