Sarcolemmal dysfunction in facioscapulohumeral dystrophy: An assessment using muscle velocity recovery cycles.

OBJECTIVE

There is a need to develop novel facioscapulohumeral dystrophy (FSHD) biomarkers for use in clinical trials. We examined the muscle excitability properties in FSHD and their use as biomarkers of disease severity.

METHODS

Muscle velocity recovery cycle (MVRC) and frequency ramp recordings were performed on the tibialis anterior (TA) and trapezius muscles in subjects with FSHD. Markers of disease severity including symptom severity, muscle dynamometry and the FSHD-COM functional scale were recorded for disease correlation. Recordings from 20 FSHD subjects were compared to 74 TA and 33 trapezius normal controls.

RESULTS

FSHD recordings from distal and proximal muscles demonstrated significantly reduced early and late muscle supernormality measures. There was a moderate correlation between late supernormality changes multiple conditioning in the trapezius and quadriceps dynamometry. Frequency ramp latency changes were significantly blunted in FSHD subjects.

CONCLUSIONS

The findings are consistent with resting muscle membrane potential depolarisation, but correlations with markers of disease severity were limited.

SIGNIFICANCE

The pathophysiology of FSHD involves not only ultrastructural changes to muscle and its supporting structures, but functional changes in the electrical properties of the muscle membrane. Muscle membrane properties are perturbed early in the disease course, and could be considered as a potential disease biomarker.