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Journal of Neurology
Published in: Journal of Neurology 8/2018

01-08-2018 | Original Communication

Cutaneous somatic and autonomic nerve TDP-43 deposition in amyotrophic lateral sclerosis

Authors: Yuting Ren, Wenxiu Liu, Yifan Li, Bo Sun, Yanran Li, Fei Yang, Hongfen Wang, Mao Li, Fang Cui, Xusheng Huang

Published in: Journal of Neurology | Issue 8/2018

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Abstract

Objective

To evaluate the involvement of the sensory and autonomic nervous system in amyotrophic lateral sclerosis (ALS) and to determine whether TDP-43/pTDP-43 deposits in skin nerve fibers signify a valuable biomarker for ALS.

Methods

Eighteen patients with ALS and 18 age- and sex-matched control subjects underwent physical examinations, in addition to donating skin biopsies from the distal leg. The density of epidermal, Meissner’s corpuscle (MC), sudomotor, and pilomotor nerve fibers were measured. Confocal microscopy was used to determine the cutaneous somatic and autonomic nerve fiber density and TDP-43/pTDP-43 deposition.

Results

Intraepidermal nerve fiber density (IENFD) was reduced in individuals with ALS (P < 0.001). MC density (MCD) (P = 0.001), sweat gland nerve fiber density (SGNFD) (P < 0.001), and pilomotor nerve fiber density (PNFD) (P < 0.001) were all reduced in ALS patients. The SGNFD correlated with the small-fiber neuropathy Symptoms Inventory Questionnaire (SFN-SIQ), VAS and age. The SFN-SIQ was higher in ALS with sensory symptoms than without sensory symptoms (P = 0.000). Furthermore, the SFN-SIQ was higher in ALS with autonomic symptoms than without autonomic symptoms (P = 0.002). SFN-SIQ was higher in ALS patients that were pTDP-43 positive than pTDP-43 negative (P = 0.04), respectively.

Conclusions

We established in the peripheral nervous system that higher SFN-SIQ and VAS was involved in ALS, indicating the loss of SGNF. The deposition of TDP-43/pTDP-43 in ALS nerve fibers may indicate an important role in the underlying pathogenesis of ALS. This observation might be used as a potential biomarker for diagnosing ALS.
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Metadata
Title
Cutaneous somatic and autonomic nerve TDP-43 deposition in amyotrophic lateral sclerosis
Authors
Yuting Ren
Wenxiu Liu
Yifan Li
Bo Sun
Yanran Li
Fei Yang
Hongfen Wang
Mao Li
Fang Cui
Xusheng Huang
Publication date
01-08-2018
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 8/2018
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-018-8897-5

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