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The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy

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 muta...

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Autores principales: Lai, Hsing-Jung, Chiang, Ya-Wen, Yang, Chih-Chao, Hsieh, Sung-Tsang, Chao, Chi-Chao, Lee, Ming-Jen, Kuo, Chung-Chin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631457/
https://www.ncbi.nlm.nih.gov/pubmed/26529114
http://dx.doi.org/10.1371/journal.pone.0141935
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author Lai, Hsing-Jung
Chiang, Ya-Wen
Yang, Chih-Chao
Hsieh, Sung-Tsang
Chao, Chi-Chao
Lee, Ming-Jen
Kuo, Chung-Chin
author_facet Lai, Hsing-Jung
Chiang, Ya-Wen
Yang, Chih-Chao
Hsieh, Sung-Tsang
Chao, Chi-Chao
Lee, Ming-Jen
Kuo, Chung-Chin
author_sort Lai, Hsing-Jung
collection PubMed
description 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.
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spelling pubmed-46314572015-11-13 The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy Lai, Hsing-Jung Chiang, Ya-Wen Yang, Chih-Chao Hsieh, Sung-Tsang Chao, Chi-Chao Lee, Ming-Jen Kuo, Chung-Chin PLoS One Research Article 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. Public Library of Science 2015-11-03 /pmc/articles/PMC4631457/ /pubmed/26529114 http://dx.doi.org/10.1371/journal.pone.0141935 Text en © 2015 Lai et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lai, Hsing-Jung
Chiang, Ya-Wen
Yang, Chih-Chao
Hsieh, Sung-Tsang
Chao, Chi-Chao
Lee, Ming-Jen
Kuo, Chung-Chin
The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy
title The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy
title_full The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy
title_fullStr The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy
title_full_unstemmed The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy
title_short The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy
title_sort temporal profiles of changes in nerve excitability indices in familial amyloid polyneuropathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631457/
https://www.ncbi.nlm.nih.gov/pubmed/26529114
http://dx.doi.org/10.1371/journal.pone.0141935
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