The temporal profiles of changes in nerve excitability indices in familial amyloid polyneuropathy
Journal
PLoS ONE
Journal Volume
10
Journal Issue
11
Pages
e0141935
ISSN
1932-6203
Date Issued
2015-11-03
Author(s)
Abstract
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. ? 2015 Lai et al. 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 credited.
SDGs
Other Subjects
myelin; prealbumin; prealbumin; adult; aged; Article; basement membrane; clinical article; controlled study; depolarization; disease course; familial amyloid polyneuropathy; female; gene mutation; heterozygote; human; hyperpolarization; male; motor nerve; nerve excitability; nerve fiber; pathophysiology; sensory nerve; sodium current; threshold electrotonus; TTR gene; ulnar nerve; axon; clinical trial; familial amyloid polyneuropathy; genetics; middle aged; motoneuron; myelin sheath; pathology; pathophysiology; sensory nerve cell; synaptic transmission; Aged; Amyloid Neuropathies, Familial; Axons; Female; Humans; Male; Middle Aged; Motor Neurons; Myelin Sheath; Prealbumin; Sensory Receptor Cells; Synaptic Transmission
Publisher
Public Library of Science
Type
journal article