Lycett Mitchell J, Kumar Kishore R, Liang Christina, Ng Karl
Department of Neurology and Clinical Neurophysiology, Royal North Shore Hospital, St Leonards NSW 2065, Australia; The University of Sydney, Camperdown NSW 2050, Australia.
The University of Sydney, Camperdown NSW 2050, Australia; Molecular Medicine Laboratory and Neurology Department, Concord Repatriation General Hospital, Hospital Rd, Concord NSW 2139, Australia; Translational Neurogenomics Group, Genomic and Inherited Disease Program, The Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia; St Vincent's Healthcare Campus, Faculty of Medicine, University of New South Wales, St Vincent's Hospital, Darlinghurst NSW 2010, Australia.
Clin Neurophysiol. 2025 May;173:86-95. doi: 10.1016/j.clinph.2025.02.272. Epub 2025 Mar 10.
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.
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.
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.
The findings are consistent with resting muscle membrane potential depolarisation, but correlations with markers of disease severity were limited.
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.
需要开发用于临床试验的新型面肩肱型肌营养不良症（FSHD）生物标志物。我们研究了FSHD患者的肌肉兴奋性特性及其作为疾病严重程度生物标志物的用途。
对FSHD患者的胫骨前肌（TA）和斜方肌进行肌肉速度恢复周期（MVRC）和频率斜坡记录。记录疾病严重程度的标志物，包括症状严重程度、肌肉测力法和FSHD-COM功能量表，以进行疾病相关性分析。将20名FSHD患者的记录与74名TA正常对照和33名斜方肌正常对照进行比较。
来自远端和近端肌肉的FSHD记录显示早期和晚期肌肉超常期测量值显著降低。斜方肌和股四头肌测力法中晚期超常期变化与多次条件刺激之间存在中度相关性。FSHD患者的频率斜坡潜伏期变化明显减弱。
这些发现与静息肌膜电位去极化一致，但与疾病严重程度标志物的相关性有限。
FSHD的病理生理学不仅涉及肌肉及其支持结构的超微结构变化，还涉及肌膜电特性的功能变化。肌膜特性在疾病过程早期受到干扰，可被视为潜在的疾病生物标志物。
