Schulz Nina, Beauvais Diane, Cauquil Cécile, Labeyrie Céline, Iliescu Iulia, Francou Bruno, Adam Clovis, Echaniz-Laguna Andoni, Leonardi Luca, Algalarrondo Vincent, Adams David, Beaudonnet Guillemette
Department of Neurology, CHU Bicêtre, APHP, Le Kremlin-Bicêtre, France.
Department of Neurology (Nerve-Muscle Unit), AOC National Reference Center for Neuromuscular Disorders, University Hospital of Bordeaux (CHU Pellegrin), Bordeaux, France.
Eur J Neurol. 2025 Jul;32(7):e70277. doi: 10.1111/ene.70277.
Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is an autosomal dominant systemic disease, with an overall poor prognosis. Markers of disease onset are urgently required to optimize the timing of treatment initiation. Nerve conduction studies (NCS) are an objective, reproducible, and non-invasive tool for following large nerve fiber involvement. Our objective was to determine whether the presence of intracutaneous amyloid deposition (ICAD) was associated with a higher risk of developing the disease, defined as a decline observed on nerve conduction studies, in a population of carriers not meeting the criteria for overt disease.
We included 98 presumed asymptomatic pathogenic variant TTR carriers with normal baseline NCS results and available follow-up testing results. Baseline evaluation included a neurological examination, short-term heart rate variability (HRV), electrochemical sweat conductance (ESC), intraepidermal nerve fiber density (IENFD), assessment of the presence of intracutaneous amyloid deposits (ICAD), and cardiac parameters. Follow-up neurological and cardiological evaluations were performed. NCS deterioration was defined as a 20% decrease in sensory nerve action potential (SNAP) in the lower limbs.
During a median follow-up of 5 years, 11/98 (11%) carriers presented a NCS deterioration. Presence of ICAD at baseline was significantly associated with NCS decline.
The presence of ICAD at baseline is associated with a subsequent NCS deterioration in presumed asymptomatic pathogenic variant TTR carriers. Skin biopsy for the analysis of amyloidosis deposit and small fiber density should be recommended in the evaluation of carriers and lead to discuss treatment initiation when abnormal, even in asymptomatic carriers.
遗传性转甲状腺素蛋白淀粉样变性（ATTRv淀粉样变性）是一种常染色体显性全身性疾病，总体预后较差。迫切需要疾病发作的标志物来优化治疗开始的时机。神经传导研究（NCS）是一种用于跟踪大神经纤维受累情况的客观、可重复且非侵入性的工具。我们的目的是确定在未达到显性疾病标准的携带者群体中，皮内淀粉样沉积（ICAD）的存在是否与疾病发生风险较高相关，该疾病定义为神经传导研究中观察到的下降。
我们纳入了98名基线NCS结果正常且有可用随访检测结果的推测无症状致病性变异TTR携带者。基线评估包括神经系统检查、短期心率变异性（HRV）、电化学汗液传导（ESC）、表皮内神经纤维密度（IENFD）、皮内淀粉样沉积（ICAD）存在情况的评估以及心脏参数。进行了随访神经学和心脏病学评估。NCS恶化定义为下肢感觉神经动作电位（SNAP）下降20%。
在中位随访5年期间，98名携带者中有11名（11%）出现NCS恶化。基线时ICAD的存在与NCS下降显著相关。
基线时ICAD的存在与推测无症状致病性变异TTR携带者随后的NCS恶化相关。在携带者评估中，应建议进行皮肤活检以分析淀粉样变性沉积和小纤维密度，并且当结果异常时，即使是无症状携带者，也应讨论开始治疗。
