Electrical Impedance Myography Detects Disease Progression over 12 to 24 Months in Facioscapulohumeral Muscular Dystrophy

OBJECTIVE: Targeted therapies for facioscapulohumeral muscular dystrophy (FSHD) are progressing through clinical trials. Electrical impedance myography (EIM) provides a noninvasive biomarker of muscle composition that may be valuable especially in early phase trials. This study evaluated EIM data from a multicenter FSHD cohort over 24 months. METHODS: Adult patients with FSHD at 8 sites underwent EIM in 6 muscles bilaterally (deltoid, biceps, triceps, vastus lateralis, tibialis anterior, and medial gastrocnemius). EIM outcomes phase and reactance (50 and 100 kHz [kilohertz] frequencies) and 50 of 211 kHz phase ratio were evaluated for reliability, correlations with clinical measures, and sensitivity to change. RESULTS: One hundred fifty-seven patients (53% male patients) were included. Test-retest reliability was excellent for all EIM outcomes (intraclass correlation coefficient [ICC] ≥0.94). Phase outcomes strongly correlated with the FSHD-composite outcome measure (FSHD-COM; r ≤ -0.69) and Motor Function Measure Domain 1 (MFM1; r ≥ 0.75); reactance outcomes exhibited moderate correlations with the FSHD-COM (r ≥ -0.41) and MFM1 (r ≤ 0.44). Mean declines in phase and phase ratio were apparent at 12 months (eg, -0.25, 95% confidence interval [CI] = -0.45 to -0.05 at 50 kHz), and further progressed through 24 months (-0.66, 95% CI = -0.92 to -0.40] at 50 kHz and -0.65 [95% CI = -0.87 to -0.44] at 100 kHz; both p < 0.0001). Reactance changes were smaller and not significant: -0.21 (95% CI = -0.44 to 0.02) at 50 kHz and -0.13 (95% CI = -0.35 to 0.10) at 100 kHz. INTERPRETATION: EIM phase outcomes are reliable, valid, and sensitive to change over 12 to 24 months, supporting their potential utility as biomarkers in FSHD clinical trials. ANN NEUROL 2026;99:1545-1554.