Annals of clinical and translational neurology · 2025
Reduced Muscular Carnosine in Proximal Myotonic Myopathy-A Pilot 1H-MRS Study.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Gussew Alexander, Kargaran Maryam, Rothe Maik, Deistung Andreas, Stoevesandt Dietrich, Wohlgemuth Walter A, Strube David, Kendzierski Thomas, Kölsch Anna Katharina, Heuschen Maurits Gerhard Abraham, Otto Markus, Mensch Alexander
Аннотация
OBJECTIVE: Myotonic dystrophy type 2 (proximal myotonic myopathy, PROMM) is a progressive multisystem disorder with muscular symptoms (proximal weakness, pain, myotonia) and systemic manifestations such as diabetes mellitus, cataracts, and cardiac arrhythmias. A hallmark feature is the selective degeneration of type-II fibers, likely driven by chronic myotonia and sustained metabolic stress. In this study, proton magnetic resonance spectroscopy (1H-MRS) was applied to assess intramuscular carnosine as a potential noninvasive marker of type-II fiber integrity, alongside extramyocellular lipids (EMCL) and intracellular pH. We hypothesized that carnosine would be reduced in PROMM as a consequence of type-II fiber loss.
METHODS: Seventy participants (27 genetically confirmed PROMM patients, 43 healthy volunteers) underwent localized 1H-MRS of the quadriceps muscle at 3 T using a short-TE PRESS sequence. To ensure reliable carnosine quantification, spectra with voxel fat fraction ≥ 40% were excluded, yielding a final cohort of 19 patients and 19 matched healthy volunteers. Metabolites were quantified relative to total creatine, and exploratory correlations were assessed.
RESULTS: PROMM patients showed significantly reduced carnosine compared with healthy volunteers (-50%, 0.05 ± 0.03 vs. 0.10 ± 0.05; p = 0.0022) and markedly elevated EMCL (threefold, 150.6 ± 80.5 vs. 48.6 ± 38.4; p = 0.0007). Intracellular pH did not differ between groups. Exploratory analysis revealed a negative correlation between carnosine and EMCL (r = -0.50, p = 0.03).
INTERPRETATION: This pilot study demonstrates that 1H-MRS can detect reduced intramuscular carnosine in PROMM, consistent with selective type-II-fiber loss. Carnosine thus emerges as a potential in vivo biomarker of fiber-type-specific degeneration. Validation in larger, longitudinal cohorts is warranted to establish its clinical and translational relevance.
METHODS: Seventy participants (27 genetically confirmed PROMM patients, 43 healthy volunteers) underwent localized 1H-MRS of the quadriceps muscle at 3 T using a short-TE PRESS sequence. To ensure reliable carnosine quantification, spectra with voxel fat fraction ≥ 40% were excluded, yielding a final cohort of 19 patients and 19 matched healthy volunteers. Metabolites were quantified relative to total creatine, and exploratory correlations were assessed.
RESULTS: PROMM patients showed significantly reduced carnosine compared with healthy volunteers (-50%, 0.05 ± 0.03 vs. 0.10 ± 0.05; p = 0.0022) and markedly elevated EMCL (threefold, 150.6 ± 80.5 vs. 48.6 ± 38.4; p = 0.0007). Intracellular pH did not differ between groups. Exploratory analysis revealed a negative correlation between carnosine and EMCL (r = -0.50, p = 0.03).
INTERPRETATION: This pilot study demonstrates that 1H-MRS can detect reduced intramuscular carnosine in PROMM, consistent with selective type-II-fiber loss. Carnosine thus emerges as a potential in vivo biomarker of fiber-type-specific degeneration. Validation in larger, longitudinal cohorts is warranted to establish its clinical and translational relevance.