Metabolic Syndrome, Neurotoxic 1-Deoxysphingolipids and Nervous Tissue Inflammation in Chronic Idiopathic Axonal Polyneuropathy (CIAP)

PLoS One. 2017 Jan 23;12(1):e0170583. doi: 10.1371/journal.pone.0170583. eCollection 2017.

Abstract

Aim: Chronic idiopathic axonal polyneuropathy (CIAP) is a slowly progressive, predominantly sensory, axonal polyneuropathy, with no aetiology being identified despite extensive investigations. We studied the potential role of the metabolic syndrome, neurotoxic 1-deoxysphingolipids (1-deoxySLs), microangiopathy and inflammation in sural nerve biopsies.

Methods: We included 30 CIAP-patients, 28 with diabetic distal symmetrical polyneuropathy (DSPN) and 31 healthy controls. We assessed standardised scales, tested for the metabolic syndrome, measured 1-deoxySLs in plasma, performed electroneurography and studied 17 sural nerve biopsies (10 CIAP; 7 DSPN).

Results: One third of the CIAP-patients had a metabolic syndrome, significantly less frequent than DSPN-patients (89%). Although the metabolic syndrome was not significantly more prevalent in CIAP compared to healthy controls, hypercholesterolemia did occur significantly more frequent. 1-deoxySLs were significantly and equally elevated in both patient groups compared to healthy controls. Mean basal lamina thickness of small endoneurial vessels and the number of CD68- or CD8-positive cells in biopsies of CIAP- and DSPN-patients did not differ significantly. However, the number of leucocyte-common-antigen positive cells was significantly increased in CIAP.

Conclusions: A non-significant trend towards a higher occurrence of the metabolic syndrome in CIAP-patients compared to healthy controls was found. 1-deoxySLs were significantly increased in plasma of CIAP-patients. Microangiopathy and an inflammatory component were present in CIAP-biopsies.

MeSH terms

  • Aged
  • Axons / pathology*
  • Case-Control Studies
  • Chronic Disease
  • Diabetic Neuropathies / complications
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / pathology
  • Female
  • Humans
  • Male
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / pathology*
  • Middle Aged
  • Polyneuropathies / complications
  • Polyneuropathies / metabolism*
  • Sphingolipids / metabolism*

Substances

  • Sphingolipids

Grants and funding

The authors received no specific funding for this work. TH received grants prior to this work from the 7th Framework Program of the European Commission (“RESOLVE”, Project number 305707; https://ec.europa.eu/research/fp7/index_en.cfm), the Swiss National Foundation SNF (Project 31003A_153390/1; http://www.snf.ch/en/Pages/default.aspx); the Dr. Wilhelm Hurka Stiftung (http://www.bvs.zh.ch/files/zh_stiftungen_20160606-k.pdf), the Novartis Foundation (http://www.novartisfoundation.org/) and the Rare Disease Initiative Zurich (“radiz”, Clinical Research Priority Program for Rare Diseases, University of Zurich; http://www.radiz.uzh.ch/de.html). KGC received a grant from the Deutsche Diabetes Gesellschaft (http://www.deutsche-diabetes-gesellschaft.de/home.html), as well as grants from the Deutsche Gesellschaft für Muskelkranke (https://www.dgm.org/) for projects unrelated to this work. PVD holds a senior clinical investigatorship from Fonds Wetenschappelijk Onderzoek-Vlaanderen (http://www.fwo.be/).