title: The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy.
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.
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsing-Jung
authors.initials: HJ
authors.lastname: Lai
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chiang
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sung-Tsang
authors.initials: ST
authors.lastname: Hsieh
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chao
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chung-Chin
authors.initials: CC
authors.lastname: Kuo
mesh_terms: D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D001369:Axons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons; D009186:Myelin Sheath / Q000473:pathology; D011228:Prealbumin / Q000235:genetics; D011984:Sensory Receptor Cells; D009435:Synaptic Transmission
chemical_list: D011228:Prealbumin