Quantifying Disease Progression in Patients With Charcot-Marie-Tooth Neuropathy Type 1A Using Quantitative Muscle MRI and Clinical Outcomes

BACKGROUND AND OBJECTIVES: Charcot-Marie-Tooth neuropathy type 1A (CMT1A) is a slowly progressive demyelinating neuropathy with distal muscle weakness and atrophy. Sensitive, objective outcome measures are needed for future clinical trials. We aimed to identify responsive imaging and clinical biomarkers in CMT1A over 24 months. METHODS: , ms), using automated 3D whole-muscle segmentation of 18 proximal and 10 distal leg muscles. Clinical outcomes comprised the Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNSv2), Overall Neuropathy Limitations Score, 32-item Motor Function Measure (MFM32), 6-Minute Walk Distance (6MWD), 10-Meter Walk Test (10MWT), 30-Second Sit-to-Stand, 9-Hole Peg Test (9HPT), MRC sum score, and isometric strength testing. Patient-reported measures included the Individualized Neuromuscular Quality of Life (INQoL), ActivLim, Fatigue Severity Scale, and Brief Pain Inventory. RESULTS: < 0.001) worsened at 24 months. Baseline distal leg PDFF (%) correlated with age, disease duration, 6MWD, 10MWT, MFM32, and MRC sum score. DISCUSSION: Distal leg PDFF (%) from 3D whole-muscle segmentation detects CMT1A progression within 12 months. Combined with the MFM32 and INQoL, these measures enable sensitive 12-month endpoints for future clinical trials in adults with CMT1A.