Department of Neurosciences and Mental Health, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal.
Faculdade de Medicina, Instituto de Fisiologia, Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa, Lisbon, Portugal.
Eur J Neurol. 2022 Mar;29(3):826-832. doi: 10.1111/ene.15176. Epub 2021 Nov 17.
Hereditary amyloidosis related to transthyretin (ATTR) is a rare and progressive disease that, despite the phenotypic heterogeneity, a length-dependent sensorimotor axonal neuropathy (ATTR-PN) is the classic hallmark. Timely diagnosis is paramount for early treatment implementation.
Sixty-nine asymptomatic gene carriers (Val30Met) were assessed during a 4-year period to identify those remaining asymptomatic versus those converting to ATTRV30M-PN. Conversion to symptomatic was defined as presenting with two definite symptoms of ATTRV30M-PN. Composite neurophysiological scores of sensory (SNS), motor (MNS), and sympathetic skin response (SSRS) amplitudes were used to assess neuropathy progression. We used mixed-effects modeling and ordinal logistic regression to assess neurophysiological evolution over time.
Of all asymptomatic gene carriers, 55.1% (n = 38/69) converted over the period of this analysis. The progression of the SNS relative to baseline was different between groups (asymptomatic gene carriers vs. converters), the decline being greater in the converter group (time × group interaction p = 0.040), starting about 2 years before symptom onset. No significant change occurred regarding MNS or SSRS. Moreover, the percentage of cases with an annual decline on the SNS of at least 25%, gradually and significantly increased in the converter group, representing a 1.92 increase in risk of developing symptoms for those with such reduction on the last evaluation.
A simple composite neurophysiological sum score can predict the onset of ATTRV30M-PN symptoms by as much as 2 years, highlighting the importance of a systematic follow-up of asymptomatic gene carriers, allowing a timely diagnosis, and management of symptomatic disease.
转甲状腺素蛋白相关遗传性淀粉样变性（ATTR）是一种罕见且进行性疾病，尽管表型存在异质性，但长度依赖性感觉运动轴索性神经病（ATTR-PN）是其经典特征。及时诊断对于早期治疗至关重要。
在 4 年期间评估了 69 名无症状基因携带者（Val30Met），以确定仍无症状的患者与转化为 ATTRV30M-PN 的患者。出现 2 项明确的 ATTRV30M-PN 症状则定义为转化为有症状。采用复合神经生理学评分（包括感觉神经（SNS）、运动神经（MNS）和交感神经皮肤反应（SSRS）振幅）评估神经病进展。我们采用混合效应模型和有序逻辑回归评估随时间的神经生理学演变。
在所有无症状基因携带者中，55.1%（n=38/69）在分析期间发生转化。与基线相比，无症状基因携带者和转化者之间 SNS 的进展不同，转化者组的下降更大（时间×组交互作用 p=0.040），在症状发作前约 2 年开始。MNS 或 SSRS 无显著变化。此外，SNS 每年下降至少 25%的病例百分比在转化者组中逐渐且显著增加，这代表最后一次评估中出现这种下降的患者发生症状的风险增加了 1.92 倍。
简单的复合神经生理学总分可以预测 ATTRV30M-PN 症状的发生，提前 2 年，这突出了对无症状基因携带者进行系统随访的重要性，以便及时诊断和管理有症状的疾病。
