Reduced Muscular Carnosine in Proximal Myotonic Myopathy-A Pilot ¹H-MRS Study

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.

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.

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).

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.