Quantitative foot muscle fat fraction increases over 12 months in young people with CMT1A

<h3>Introduction</h3> Quantitative muscle fat fraction(FF) at calf is a responsive biomarker in CMT1A.^{1 2} Lower responsiveness was seen in those with baseline FF &lt;10%, who were younger and had lower CMTES.² We evaluated foot MRI as an outcome measure in these patients. <h3>Methods</h3> 22 participants with CMT1A and 14 age-matched controls (aged 6–20) were recruited in London and Iowa (p=0.58) completing clinical assessments and foot neuromuscular MRI. Blinded segmentation allowed MRI analysis. <h3>Results</h3> 16/22 participants with CMT1A (348–902 days, mean 522, s.d.163), and 11/14 controls (range 355–892 days, mean 476, s.d.174) returned for follow-up. Baseline coronal forefoot mean Dixon FF (standardised to 365 days, presented mean±s.d.) for controls is 3.5±1.4% without annual change 0.88±0.67%. Calf FF did not change in either group. In CMT1A patients mean baseline FF was 25.9±20.8% increasing 2.0±2.4%, p=0.001. High responsiveness was confirmed with standardised response mean 0.86. Baseline foot FF in patients correlated with age ρ=0.59, p=0.008, and CMTES ρ=0.58 p=0.01. <h3>Conclusions</h3> Baseline forefoot FF was higher in patients (25.9%) than controls (3.6%) and increased over 365-days in patients, with high responsiveness. We have demonstrated that coronal foot FF is a viable outcome measure for clinical trials in children and young people who have CMT1A. <h3>References</h3> Morrow, <i>et al.</i> MRI biomarker assessment of neuromuscular disease progression: prospective observational cohort study. <i>Lancet Neurol</i> 2016 Jan;<b>15</b>(15):65–77. Morrow, <i>et al</i>.Validation of MRCCentre MRI calf muscle FF protocol as outcome measure in CMT1A. <i>Neurology</i> 2018;<b>0</b>:10.1212.