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Muscle MRI May Serve as Sensitive Biomarker for ALS Disease Progression
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Key Takeaways
- Longitudinal quantitative MRI detects progressive muscle atrophy in ALS, correlating with muscle strength loss and disease progression.
- Muscle MRI shows potential as a biomarker for ALS progression and could reduce clinical trial size and duration.
A study involving 20 patients with ALS found that longitudinal muscle MRI detected progressive atrophy and correlated with muscle strength loss, supporting its potential as a biomarker for ALS progression and clinical trials.
Pietro Fratta, PhD
In a recently published small-scale study, findings showed that longitudinal quantitative MRI reliably detects progressive atrophy and decrease of functional rest muscle area in patients with amyotrophic lateral sclerosis (ALS), which correlated with progressive loss of muscle strength and global disease progression. All told, these data point to the potential of muscle MRI to be utilized as a biomarker for ALS disease progression as well as a helpful tool for reducing the size and duration of future drug clinical trials.1
The study, featuring 20 patients with ALS and 16 healthy controls, tested correlations between quantitative MRI parameters cross-sectional (CSA), volume (VOL), fat fraction, functional rest muscle area, and water T2 (T2m) with changes in functional rating scales and myometry. Each patient underwent muscle MRI of the upper and lower limbs as well as the head-neck region at 3 time points over the individual maximum observation period (iMOP) of 1 year.
Senior author Pietro Fratta, PhD, an MRC senior fellow and MNDA Lady Edith Wolfson fellow at the UCL Queen Square Institute of Neurology, and colleagues, found that in patients with ALS, thigh CSA significantly decreases (partial n2 = 0.56; T(1,16) = 4.51; P <.001) over the iMOP. Similarly, the authors also observed declines in calf CSA (partial n2 = 0.54; T(1,16) = 4.30; P <.001) and hand muscle volume (rs = 0.66; test statistic = –122; P <.001). Furthermore, at the head-neck level, the volume of the bilateral pterygoideus lateralis muscle declined significantly over the iMOP (partial n2 = 0.47; T(1,15) = 3.67; P = .002).
"To our knowledge, this is the first study to conduct a comprehensive longitudinal analysis of MRI parameters muscle atrophy, fRMA and oedema across limb, hand and bulbar muscles in ALS, and to correlate these changes with functional and clinical measures," Fratta et al wrote. "Furthermore, this represents the largest muscle MRI-based study to date investigating progressive quantifiable muscle atrophy in ALS, providing a robust foundation for future biomarker development."
Functional rest muscle area (fRMA) significantly decreases at both thigh (partial n2 = 0.57; T(1,16) = 4.57; P <.001) and calf levels (partial n2 = 0.57; T(1,15) = 4.42; P <.001), with the highest responsiveness observed for fRMA thigh (standardized rate mean [SRM], 1.11) and fMRA calf (SRM, 1.10). Notably, T2m, used to assess the extent of muscle oedema, was trending toward decrease over time at high and calf level over the iMOP (Bonferroni-corrected, P >.003).
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When analyzing the link between muscle MRI changes and disease severity, investigators found that the relative decrease of fRMA of anterior thigh muscle compartment (ANT-TMC) significantly correlated with the relative decrease of knee extension strength over time (r = 0.77; P <.001). In the calf, the relative decrease of fRMA of the triceps surae muscles were found to significantly correlate with the relative decrease of planta flexion strength over the iMOP (r = 0.78; P <.001).
In the study, investigators observed a significant correlation between the overall relative decrease of fRMA and the decrease of ALS Functional Rating Scale (ALSFRS) total score over the iMOP at the calf level (r = 0.68; P = .004). For the thigh level, this correlation ultimately did not withstand Bonferroni adjustment (P >.004). At the hand level, the relative decrease in VOL significantly correlated with the corresponding decrease in grip strength over time (r = 0.71; P = .004) while correlations between VOL hand and ALSFRS handshowed a trend (Bonferroni-corrected, P >0.00).
"Patient survival is frequently used as an endpoint in clinical trials of ALS,13 but objective markers of disease progression may reduce the size and duration of future trials,” the study authors wrote. “We demonstrate that MRI-quantified atrophy of the hand and lower limbs showed the highest responsiveness to detect disease progression, further validated by strong correlation with patient muscle strength and functional scores."
Fratta et al added, "Our findings might have a substantial impact on the design of future clinical trials in ALS, potentially allowing a reduced number of participants needed to detect effects, with the ultimate goal of facilitating the development and approval of therapeutic agents in ALS. There is an urgent need for the development of new drugs in ALS, and our longitudinal study contributes to a small but fast-rising field of muscle MRI in MND and supports its integration in future interventional trials."
