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

作者：Iterbeke L, Huysmans L, Bamps K, Peeters R, Goosens V, Maes F, Dupont P, Claeys KG · 发表于：Neurology · 年份：2026 · DOI：10.1212/WNL.0000000000218411 · 被引用次数：39 · 研究领域：Charcot-Marie-Tooth Disease、Magnetic Resonance Imaging、Muscle, Skeletal、Humans、Female、Male、Adult、Disease Progression、Middle Aged、Prospective Studies

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: In this prospective, monocentric natural history study, ambulatory adults with genetically confirmed CMT1A and healthy controls were enrolled for 3 visits (baseline, 12, and 24 months). Quantitative muscle MRI quantified proton density fat fraction (PDFF, %) and disease activity with water T2 (T2H2O, 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: Thirty-three patients with CMT1A (43.8 years, 64% female) and 33 controls (42.2 years, 61% female) were included. At baseline, PDFF (%) was elevated in CMT1A across all leg muscles (p < 0.001). Distal leg PDFF (%) increased at 12 months (+1.1%, 95% CI 0.7-1.4, p < 0.001) and 24 mo...