Autonomic and peripheral neuropathy with reduced intraepidermal nerve fiber density can be observed in patients with gastrointestinal dysmotility

[pattismith]

Autonomic and peripheral neuropathy with reduced intraepidermal nerve fiber density can be observed in patients with gastrointestinal dysmotility
Dec 2019

Abstract

Neuropathy should be considered as a possible etiological factor in patients with severe gastrointestinal symptoms, without signs of disease on routine investigations. Examinations of the autonomic and peripheral nervous systems may be helpful to select the patients who should be investigated with full‐thickness intestinal biopsy, and to give appropriate care.


1 INTRODUCTION

Severe gastrointestinal (GI) dysmotility in the form of chronic intestinal pseudo‐obstruction (CIPO) and enteric dysmotility (ED) are rare diseases, which are difficult to diagnose.1 Enteric neuropathy, leading to dysmotility, is seldom studied, since there are few centers available for evaluation of GI motility. Furthermore, there are difficulties to get access to myenteric plexus of the enteric nervous system, and the histopathological examination of tissue samples is time‐consuming.

Subsequently, most patients with GI dysmotility and pain are diagnosed to have irritable bowel syndrome (IBS), or the neuropathy diagnosis is delayed for several years.2, 3

Due to different treatment strategies between GI dysmotility and IBS, it is important to diagnose the diseases correctly. Functional bowel diseases are mainly treated with dietary advice in the form of regular meals with carbohydrate restriction and psychological therapy,4 whereas dysmotility is treated with prokinetic drugs and dietary supplemental therapy.5

Previous reports have shown signs of autonomic neuropathy and serum antibodies against neural components in patients with CIPO and ED.3, 6

Furthermore, autonomic and peripheral neuropathy are associated, for example, in diabetes mellitus.7

This has led to the hypothesis that examination of the autonomic and peripheral nervous systems could be used, to select candidates for full‐thickness intestinal biopsy, and to facilitate the differentiation between patients with neuropathic dysmotility and IBS.

The present double case report describes two women with severe GI dysmotility during several years, confirmed by examinations of GI motility and full‐thickness biopsy with immunohistochemical staining. In 2018, examinations with specific questionnaires regarding symptoms of autonomic and peripheral dysfunction, along with autonomic nerve function tests and skin biopsies, were performed to examine the autonomic and peripheral nervous systems.

Patients with gastrointestinal dysmotility may have symptoms and signs of a more generalized neuropathy. Besides examining the gut function, also the autonomic and peripheral nerve functions with determination of the intraepidermal nerve fiber density should be tested, to select patients for full‐thickness intestinal biopsies and to handle the patients appropriately.

 

[kangaSue]

Interestingly, I read it hypothesised in a GI dysmotility paper a while ago that IBS could just be the mild end of CIPO (Chronic intestinal pseudo obstruction). Not sure which paper I read it in now though.

My GI (who I was seeing for gastroparesis) said I didn't have other symptoms and signs of a more generalized neuropathy either, but from doing an autonomic function test panel that included a TTT and Heart Rate variability to Deep Breathing Test (and sweat tests of QSART and TST), a diagnosis of Autonomic Neuropathy was added to the mix from the abnormal results returned.

 

[pattismith]

Interestingly, I read it hypothesised in a GI dysmotility paper a while ago that IBS could just be the mild end of CIPO (Chronic intestinal pseudo obstruction). Not sure which paper I read it in now though.

My GI (who I was seeing for gastroparesis) said I didn't have other symptoms and signs of a more generalized neuropathy either, but from doing an autonomic function test panel that included a TTT and Heart Rate variability to Deep Breathing Test (and sweat tests of QSART and TST), a diagnosis of Autonomic Neuropathy was added to the mix from the abnormal results returned.

kanga, did you receive a skin biopsy at a time or another ?

I suspect I have some ancient SFN with early involvement of small autonomic fibers that spread progressively to small sensory fibers to muscle and that small sensory fibers to skin got involved only recently, which could explain why I was not aware of this disease before I suddenly felt the tingling/numbness/warm in my hands and feet.
It's only an hypothesis though, as I have no idea if the course of the SFN can go down this progressive road!
But it would match with my progressive symptoms, starting in the stomach/gut dyscomfort, spreading to muscles/pain then spine/pain, then arriving many years later to sensory skin disturbance….

 

[kangaSue]

kanga, did you receive a skin biopsy at a time or another ?

No, I haven't had a skin punch biopsy. It was enough for me to know that I had Autonomic Neuropathy.

Disregarding that it's a sarcoidosis article, there's some helpful info about SFN symptoms in the following paper, particularly the passage I have copied and pasted;

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523152/
[Small fiber neuropathy (SFN) is a peripheral nerve disorder that selectively affects thinly myelinated Aδ fibers and unmyelinated C fibers. Small nerve fibers are involved in both somatic and autonomic function. As a result, patients with SFN may present with symptoms of neuropathic pain (NP) and autonomic dysfunction. The character of the pain can be burning or shooting.

Damage to or loss of small somatic nerve fibers results in burning pain, tingling, or numbness that typically affects the limbs in a distal to proximal gradient. Symptoms are usually worse at night and often affect sleep.

When autonomic fibers are affected, patients may experience dry eyes, dry mouth, orthostatic dizziness, constipation, bladder incontinence, sexual dysfunction, hyperhidrosis or hypohidrosis, or red or white skin discoloration. Finally restless legs syndrome may be present, characterized by disagreeable leg sensations that usually occur prior to sleep onset and cause an almost irresistible urge to move.

Most patients suffer from length-dependent small-fiber neuropathy (LD-SFSN): symptoms and signs start to develop in the toes and feet, symptoms gradually progress to involve distal legs, fingertips, and hands. Non-length-dependent small-fiber neuropathy (NLD-SFSN) is not as common as LD-SFSN and patients develop complaints in a patchy distribution. This can include face, upper limbs, or trunk before the lower limbs are affected. The NLD-SFSN is more seen in women and presents at a younger age.]