Effect of sirolimus on muscle in inclusion body myositis observed with magnetic resonance imaging and spectroscopy.

Autor: Reyngoudt H; NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France., Baudin PY; NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France., Caldas de Almeida Araújo E; NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France., Bachasson D; Neuromuscular Physiology and Evaluation Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.; INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, Paris, France., Boisserie JM; NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France., Mariampillai K; Department of Internal Medicine and Clinical Immunology, Inflammatory Myopathies Reference Center, Research Center in Myology UMR974, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France.; I-Motion, Institute of Myology, Paris, France., Annoussamy M; I-Motion, Institute of Myology, Paris, France., Allenbach Y; Department of Internal Medicine and Clinical Immunology, Inflammatory Myopathies Reference Center, Research Center in Myology UMR974, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France., Hogrel JY; Neuromuscular Physiology and Evaluation Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France., Carlier PG; CEA, DRF, SHFJ, University Paris-Saclay, Orsay, France., Marty B; NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France., Benveniste O; Department of Internal Medicine and Clinical Immunology, Inflammatory Myopathies Reference Center, Research Center in Myology UMR974, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France.
Jazyk: angličtina
Zdroj: Journal of cachexia, sarcopenia and muscle [J Cachexia Sarcopenia Muscle] 2024 Jun; Vol. 15 (3), pp. 1108-1120. Date of Electronic Publication: 2024 Apr 13.
DOI: 10.1002/jcsm.13451
Abstrakt: Background: Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1-year longitudinal data from quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy ( 31 P MRS) in a placebo-controlled study of sirolimus for inclusion body myositis (IBM), also examining their links to functional, strength, and clinical parameters in lower limb muscles.
Methods: Quantitative MRI and 31 P MRS data were collected at 3 T from a single site, involving 44 patients (22 on placebo, 22 on sirolimus) at baseline and year-1, and 21 healthy controls. Assessments included fat fraction (FF), contractile cross-sectional area (cCSA), and water T 2 in global leg and thigh segments, muscle groups, individual muscles, as well as 31 P MRS indices in quadriceps or triceps surae. Analyses covered patient-control comparisons, annual change assessments via standard t-tests and linear mixed models, calculation of standardized response means (SRM), and exploration of correlations between MRI, 31 P MRS, functional, strength, and clinical parameters.
Results: The quadriceps and gastrocnemius medialis muscles had the highest FF values, displaying notable heterogeneity and asymmetry, particularly in the quadriceps. In the placebo group, the median 1-year FF increase in the quadriceps was 3.2% (P < 0.001), whereas in the sirolimus group, it was 0.7% (P = 0.033). Both groups experienced a significant decrease in cCSA in the quadriceps after 1 year (P < 0.001), with median changes of 12.6% for the placebo group and 5.5% for the sirolimus group. Differences in FF and cCSA changes between the two groups were significant (P < 0.001). SRM values for FF and cCSA were 1.3 and 1.4 in the placebo group and 0.5 and 0.8 in the sirolimus group, respectively. Water T 2 values were highest in the quadriceps muscles of both groups, significantly exceeding control values in both groups (P < 0.001) and were higher in the placebo group than in the sirolimus group. After treatment, water T 2 increased significantly only in the sirolimus group's quadriceps (P < 0.01). Multiple 31 P MRS indices were abnormal in patients compared to controls and remained unchanged after treatment. Significant correlations were identified between baseline water T 2 and FF at baseline and the change in FF (P < 0.001). Additionally, significant correlations were observed between FF, cCSA, water T 2 , and functional and strength outcome measures.
Conclusions: This study has demonstrated that quantitative MRI/ 31 P MRS can discern measurable differences between placebo and sirolimus-treated IBM patients, offering promise for future therapeutic trials in idiopathic inflammatory myopathies such as IBM.
(© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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