AP-HP, Service de neurologie, CHU Bicêtre, Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares, CERAMIC, FILNEMUS Network, 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.
J Neurol Neurosurg Psychiatry. 2024 May 14;95(6):489-499. doi: 10.1136/jnnp-2023-332180.
Hereditary transthyretin amyloidosis is a life-threatening autosomal dominant systemic disease due to pathogenic variants (ATTRv), mostly affecting the peripheral nerves and heart. The disease is characterised by a combination of symptoms, organ involvement and histological amyloid deposition. The available disease-modifying ATTRv treatments (DMTs) are more effective if initiated early. Pathological nerve conduction studies (NCS) results are the cornerstone of large-fibre polyneuropathy diagnosis, but this anomaly occurs late in the disease. We investigated the utility of a multimodal neurological and cardiac evaluation for detecting early disease onset in ATTRv carriers.
We retrospectively analysed a cohort of ATTRv carriers with normal NCS results regardless of symptoms. Multimodal denervation and infiltration evaluations included a clinical questionnaire (Lauria and New York Heart Association (NYHA)) and examination, intra-epidermal nerve fibre density assessment, autonomic assessment based on heart rate variability, Sudoscan, meta-iodo-benzyl-guanidine scintigraphy, cardiac biomarkers, echocardiography, MRI and searches for amyloidosis on skin biopsy and bone scintigraphy.
We included 130 ATTRv carriers (40.8% men, age: 43.6±13.5 years), with 18 amyloidogenic gene mutations, the majority of which was the late-onset Val30Met variant (42.3%). Amyloidosis was detected in 16.9% of mutation carriers, including 9 (6.9%) with overt disease (Lauria>2 or NYHA>1) and 13 asymptomatic carriers (10%) with organ involvement (small-fibre neuropathy or cardiomyopathy). Most of these patients received DMT. Abnormal test results of unknown significance were obtained for 105 carriers (80.8%). Investigations were normal in only three carriers (2.3%).
Multimodal neurological and cardiac investigation of TTRv carriers is crucial for the early detection of ATTRv amyloidosis and initiation of DMT.
遗传性转甲状腺素蛋白淀粉样变性病是一种危及生命的常染色体显性系统性疾病，由致病性变异（ATTRv）引起，主要影响外周神经和心脏。该疾病的特征是多种症状、器官受累和组织学淀粉样沉积的组合。如果早期开始，现有的可改变疾病转甲状腺素蛋白淀粉样变性病（ATTRv）治疗（DMT）更有效。病理学神经传导研究（NCS）结果是大纤维多发性神经病诊断的基石，但这种异常在疾病晚期才出现。我们研究了多模式神经和心脏评估在检测 ATTRv 携带者早期发病中的作用。
我们回顾性分析了一组 NCS 结果正常（无论有无症状）的 ATTRv 携带者的队列。多模式去神经和浸润评估包括临床问卷（Lauria 和纽约心脏协会（NYHA））和检查、表皮内神经纤维密度评估、基于心率变异性的自主神经评估、Sudoscan、meta-碘代苄胍闪烁显像、心脏生物标志物、超声心动图、MRI 以及皮肤活检和骨闪烁显像寻找淀粉样变性。
我们纳入了 130 名 ATTRv 携带者（40.8%为男性，年龄：43.6±13.5 岁），有 18 种淀粉样变性基因突变，其中大多数为迟发性 Val30Met 变异（42.3%）。16.9%的突变携带者检测到淀粉样变性，其中 9 名（6.9%）有显性疾病（Lauria>2 或 NYHA>1），13 名无症状携带者（10%）有器官受累（小纤维神经病或心肌病）。这些患者大多数接受了 DMT。105 名携带者（80.8%）的检查结果异常，但意义不明。只有 3 名携带者（2.3%）的检查结果正常。
对 TTRv 携带者进行多模式神经和心脏检查对于早期发现 ATTRv 淀粉样变性和开始 DMT 至关重要。
