Study of Autophagy and Microangiopathy in Sural Nerves of Patients with Chronic Idiopathic Axonal Polyneuropathy.

Kristin Samuelsson,Simin Mohseni,Maria Angeria,Ayman A M Osman,Mårten Risling,Rayomand Press

doi:10.1371/journal.pone.0163427

Kristin Samuelsson, Simin Mohseni + Show 4 more

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https://doi.org/10.1371/journal.pone.0163427

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Abstract

Twenty-five percent of polyneuropathies are idiopathic. Microangiopathy has been suggested to be a possible pathogenic cause of chronic idiopathic axonal polyneuropathy (CIAP). Dysfunction of the autophagy pathway has been implicated as a marker of neurodegeneration in the central nervous system, but the autophagy process is not explored in the peripheral nervous system. In the current study, we examined the presence of microangiopathy and autophagy-related structures in sural nerve biopsies of 10 patients with CIAP, 11 controls with inflammatory neuropathy and 10 controls without sensory polyneuropathy. We did not find any significant difference in endoneurial microangiopathic markers in patients with CIAP compared to normal controls, though we did find a correlation between basal lamina area thickness and age. Unexpectedly, we found a significantly larger basal lamina area thickness in patients with vasculitic neuropathy. Furthermore, we found a significantly higher density of endoneurial autophagy-related structures, particularly in patients with CIAP but also in patients with inflammatory neuropathy, compared to normal controls. It is unclear if the alteration in the autophagy pathway is a consequence or a cause of the neuropathy. Our results do not support the hypothesis that CIAP is primarily caused by a microangiopathic process in endoneurial blood vessels in peripheral nerves. The significantly higher density of autophagy structures in sural nerves obtained from patients with CIAP and inflammatory neuropathy vs. controls indicates the involvement of this pathway in neuropathy, particularly in CIAP, since the increase in density of autophagy-related structures was more pronounced in patients with CIAP than those with inflammatory neuropathy. To our knowledge this is the first report investigating signs of autophagy process in peripheral nerves in patients with CIAP and inflammatory neuropathy.

Highlights

Polyneuropathy is a common neurological condition due to disturbed function of the peripheral nerves
Fascicular sural nerve biopsies obtained from patients with idiopathic axonal sensorimotor polyneuropathy, and age and gender-matched controls consisting of patients with inflammatory neuropathy and 10 controls without sensory polyneuropathy were used for this study
There were no significant differences between the groups regarding risk factors for vascular disease such as smoking, metabolic and cardiovascular diseases, or other clinical parameters such as pain and the need for a walking aid

Summary

Introduction

Polyneuropathy is a common neurological condition due to disturbed function of the peripheral nerves. Similar changes have been shown in patients with atherosclerotic peripheral vascular disease without diabetes as an indication of attribution of chronic ischemia for the pathogenesis of the structural abnormalities [25]. There is very limited data available on histopathological characterization of peripheral nerves in patients with CIAP. Another possible contributing factor to the pathogenesis of CIAP may be age-related axonal degeneration causing disturbed axonal structure or function, as suggested by the fact that the incidence of CIAP correlates positively with age. An alternative cause of axonal degeneration in peripheral nerves in CIAP may be genetic mutations in axonal genes This notion is supported by the identification of the mutation in the gene coding for neurofilament light chain, causing disruption in the axonal cytoskeleton and leading to hereditary motor sensory neuropathy (HMSN) type 2E [26]

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