Berard Nicolas, Verschueren Annie, Fortanier Etienne, Grapperon Aude-Marie, Kouton Ludivine, Rebouh Hadia, Gallard Julien, Salort-Campana Emmanuelle, Attarian Shahram, Delmont Emilien
Referral Centre for Neuromuscular Diseases and ALS, La Timone University Hospital, Aix-Marseille University, ERN Neuro-NMD, Marseille, France.
Muscle Nerve. 2025 Feb;71(2):208-215. doi: 10.1002/mus.28318. Epub 2024 Dec 12.
INTRODUCTION/AIMS: It is imperative to screen asymptomatic carriers of transthyretin (TTR) mutations to initiate treatment early. The protocol for repeated electrodiagnostic (EDX) assessments over time lacks standardization. Our aim was to report the electrophysiological evolution of a cohort of asymptomatic carriers and to determine which biomarkers were most sensitive to change.
We performed a retrospective review of medical records of asymptomatic carriers identified by screening families with amyloid neuropathy. Carriers who underwent two EDX assessments with a minimum 1-year interval between studies were selected. EDX included analysis of median, ulnar, tibial, fibular and sural nerves, motor unit number index (MUNIX), electrochemical skin conductance, sympathetic skin response, and heart rate variability on deep breathing. Measurements were compared at first and second examinations.
Twenty-three carriers were included with a median age of 49 years (interquartile range 37-58). Median time between examinations was 3 years (2-4). Compound muscle and sensory nerve action potential (CMAP and SNAP) amplitudes, nerve conduction velocities, autonomic small fiber testing and MUNIX remained stable except for motor distal latency of the median nerve (+0.07 ms/year) and CMAP duration of the ulnar (+0.10 ms/year) and fibular (+0.12 ms/year) nerves. The CMAP duration of the ulnar nerve was the most sensitive biomarker to change when performed within 10 years preceding the age of the youngest case in the family, with a standardized response mean of 0.91.
Nerve conduction parameters remain relatively stable in asymptomatic TTR carriers. Changes can only be detected using multimodal and extensive electrophysiological tests.
引言/目的：筛查无症状的转甲状腺素蛋白（TTR）突变携带者以便尽早开始治疗至关重要。随着时间推移进行重复电诊断（EDX）评估的方案缺乏标准化。我们的目的是报告一组无症状携带者的电生理演变情况，并确定哪些生物标志物对变化最敏感。
我们对通过筛查患有淀粉样神经病的家庭而确定的无症状携带者的病历进行了回顾性研究。选择了在两次研究之间间隔至少1年进行两次EDX评估的携带者。EDX包括对正中神经、尺神经、胫神经、腓神经和腓肠神经的分析、运动单位数量指数（MUNIX）、电化学皮肤电导、交感皮肤反应以及深呼吸时的心率变异性。对首次和第二次检查的测量结果进行了比较。
纳入了23名携带者，中位年龄为49岁（四分位间距37 - 58岁）。两次检查之间的中位时间为3年（2 - 4年）。复合肌肉和感觉神经动作电位（CMAP和SNAP）振幅、神经传导速度、自主神经小纤维检测和MUNIX保持稳定，但正中神经运动远端潜伏期（每年增加0.07毫秒）以及尺神经（每年增加0.10毫秒）和腓神经（每年增加0.12毫秒）的CMAP持续时间除外。在家族中最年轻病例年龄之前的10年内进行检测时，尺神经的CMAP持续时间是对变化最敏感的生物标志物，标准化反应均值为0.91。
在无症状的TTR携带者中，神经传导参数相对稳定。只有使用多模式和广泛的电生理测试才能检测到变化。
