The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy.
The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy.
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DOI：
10.1371/journal.pone.0141935
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kuo CC
中科院分区：
文献类型：
--
作者：
Lai HJ;Chiang YW;Yang CC;Hsieh ST;Chao CC;Lee MJ;Kuo CC
家族性淀粉样多发性神经病（FAP）是由甲状腺素运载蛋白（TTR）基因突变引起的一种常染色体显性遗传病。本研究旨在探讨FAP的病理生理机制。我们前瞻性招募了12名症状较轻的携带者、18名携带TTR突变p.A97S的患者和两个年龄匹配的对照组。收集尺神经运动和感觉轴突的神经兴奋性试验（NET）数据，患者尺神经运动轴突的NET研究显示阈值和基强度增加，超极化阈值电紧张（TE）时阈值升高降低，不应期增加。在感觉神经研究中，去极化TE的阈值降低增加，超极化TE后恢复斜率降低和超调时间延迟，恢复周期中的不应性和超兴奋性增加。携带者尺神经的NET曲线显示阈值和基强度增加，而超极化TE和超兴奋性阈值无明显变化。回归模型表明，不应期的增加和相对不应期的延长与从携带者到患者的疾病进展相关。短宽度刺激时不应性的显著增加表明钠电流的缺陷，这可能代表TTR-FAP的早期症状前病理生理变化。基底层和髓鞘的局灶性破坏可能进一步增加结间容量，表现为超极化TE后恢复斜率降低和超调时间延迟以及超兴奋性增加。因此，NET可以成为一个实用的工具，从TTR-FAP的早期阶段监测疾病的进展。
Familial amyloid polyneuropathy (FAP) caused by a mutation in transthyretin (TTR) gene is an autosomal dominant inherited disorder. The aim of this study is to explore the pathophysiological mechanism of FAP. We prospectively recruited 12 pauci-symptomatic carriers, 18 patients who harbor a TTR mutation, p.A97S, and two-age matched control groups. Data of nerve excitability test (NET) from ulnar motor and sensory axons were collected.NET study of ulnar motor axons of patients shows increased threshold and rheobase, reduced threshold elevation during hyperpolarizing threshold electrotonus (TE), and increased refractoriness. In sensory nerve studies, there are increased threshold reduction in depolarizing TE, lower slope of recovery and delayed time to overshoot after hyperpolarizing TE, increased refractoriness and superexcitability in recovery cycle. NET profiles obtained from the ulnar nerve of carriers show the increase of threshold and rheobase, whereas no significant threshold changes in hyperpolarizing TE and superexcitability. The regression models demonstrate that the increase of refractoriness and prolonged relative refractory period are correlated to the disease progression from carriers to patients. The marked increase of refractoriness at short-width stimulus suggests a defect in sodium current which may represent an early, pre-symptomatic pathophysiological change in TTR-FAP. Focal disruption of basal lamina and myelin may further increase the internodal capacity, manifested by the lower slope of recovery and delayed time to overshoot after hyperpolarization TE as well as the increase of superexcitability. NET could therefore make a pragmatic tool for monitoring disease progress from the very early stage of TTR-FAP.