Muscle MRI as a biomarker of disease activity and progression in myotonic dystrophy type 1: a longitudinal study

Abstract

Introduction: Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease characterized by myotonia and progressive muscular weakness and atrophy. The aim of this study was to investigate the usefulness of longitudinal muscle MRI in detecting disease activity and progression in DM1, and to better characterize muscle edema, fat replacement and atrophy overtime.

Materials and methods: This is a prospective, observational, longitudinal study including 25 DM1 patients that performed at least two muscle MRIs. Demographic and genetic characteristics were recorded. Muscular Impairment Rating Scale (MIRS) and MRC score were performed within 3 months from MRIs at baseline (BL) and at follow-up (FU). We analysed 32 muscles of lower body (LB) and 17 muscles of upper body (UB) by T1 and STIR sequences. T1-, STIR- and atrophy scores and their variations were evaluated. Correlations between MRIs' scores and demographic, clinical and genetic characteristics were analysed.

Results: Eighty (80%) of patients showed fat replacement progression at FU. The median T1 score progression (ΔT1-score) was 1.3% per year in LB and 0.5% per year in UB. The rate of fat replacement progression was not homogenous, stratifying patients from non-progressors to fast progressors (> 3% ΔT1-score per year). Half of the STIR-positive muscles at BL showed T1-score progression at FU. Two patients with normal MRI at baseline only showed STIR-positive muscle at FU, marking the disease activity onset. STIR positivity at baseline correlated with fat replacement progression (ΔT1-score; p < 0.0001) and clinical worsening at FU (ΔMRC-score; p < 0.0001). Sixty-five (65%) of patients showed STIR- and fat replacement-independent muscle atrophy progression, more evident in UB.

Conclusions: Muscle MRI represents a sensitive biomarker of disease activity, severity, and progression in DM1. STIR alterations precede fat replacement and identify patients with a higher risk of disease progression, while T1-sequences reveal atrophy and fat replacement progression before clinical worsening.

Keywords: Biomarkers; Longitudinal study; Muscle MRI; Myotonic dystrophy type 1.

Fig. 1

T1-score and Atrophy-score progression. On the left, overall T1- (A) and Atrophy-score (B) variation at FU for each patient. In the middle, T1- (A) and Atrophy-score (B) variation for each patient according to months at follow-up MRI. On the right, graphic representation of percentage of non-, mild-, moderate- and fast progressors

Fig. 2

STIR-dependent fat replacement progression. A significant correlation between STIR positivity at BL and fat replacement progression at FU (ΔT1%). B Number of muscles progressed (blue) and not progressed (red) in T1 sequences at FU, accordingly to STIR positivity/negativity at 1st MRI

Fig. 3

Muscle MRI findings. Axial plane of lower limbs in STIR and T1 sequences at BL and FU: STIR-positive right vastus medialis and left soleus at BL (yellow arrows) showed fat replacement progression in T1 sequences at FU study (red arrowheads) and still STIR-positive signal at FU (orange arrows); similarly STIR-positive right tibialis anterior at BL (yellow asterisks) showed T1 progression with complete fat replacement (red asterisks) but STIR negative (orange dot) at FU (P15, 36 years-old male at first MRI, FU duration 38 months, MIRS 3, E2 expansion class)

Fig. 4

Segmental Heatmap. Overlapped STIR positivity (red or not) and T1-score (blue scale) of at BL and at FU for each patient and each muscle; note the good overlapping between T1 progression (darker blu) at FU and STIR positivity at BL and FU

Fig. 5

Atrophy progression. STIR-independent atrophy-progression of pectoralis minor at first (up) and last (down) MRI study after 37 months (P6, 20 years-old male, FU duration 37, months, MIRS 3, E2 expansion class)