Review Article
Peripheral neuropathy in idiopathic Parkinson's disease: A systematic review

https://doi.org/10.1016/j.jns.2017.05.023Get rights and content

Highlights

  • The prevalence of large fiber neuropathy in idiopathic PD is estimated to be 16%.

  • The role of levodopa on the development of PN is still unclear.

  • Large studies with neurophysiologically confirmed neuropathy in PD are needed.

Abstract

Background

Parkinson's disease (PD) has been associated with peripheral neuropathy (PN). PN has been demonstrated in some rare genetic forms of PD (e.g. PARK2 mutations) but has also been linked to levodopa exposure.

Objective

The aim of this systematic review is to clarify any evidence of peripheral nervous system involvement in idiopathic PD.

Methods

A systematic computer-based literature search was conducted on PubMed database.

Findings

The pooled estimate of the prevalence of large fiber PN in PD was 16.3% (based on 1376 patients). The pooled estimate of the prevalence of biopsy-proven small fiber neuropathy was 56.9% (based on 72 patients).

Large fiber PN in PD is in the majority of cases distal, symmetrical, axonal and predominantly sensory. There are, however, few reports of chronic idiopathic demyelinating polyneuropathy and very occasional cases of acute neuropathies. Although nerve conduction studies have been performed in the majority of the studies, they included only a limited number of nerves, mainly in the lower limbs.

There is little evidence to support a direct link between levodopa treatment and the development of PN in idiopathic PD. In the majority of the cases PN has been linked to abnormalities in vitamin B12, methylmalonic acid or fasting homocysteine levels. Additional aetiological risk factors for PN may be responsible for any apparent link between PD and PN.

Conclusions

Large-scale prospective studies with long-term follow-up with detailed baseline assessments are needed in order to understand the natural history of PN in PD, both on clinical and neurophysiological parameters.

Introduction

The term peripheral neuropathy (PN) refers to any disorder of the peripheral nervous system including single and multiple mononeuropathies (i.e. mononeuritis multiplex), symmetrical involvement of many nerves (polyneuropathy) or isolated involvement of sensory ganglia (ganglionopathies) [1]. Further classification depends on a mixture of phenomenological, neurophysiological, pathological and aetiological parameters [2]. There is sparse robust epidemiological data on polyneuropathies of any cause in the general population, the current estimates being between 2.4% and 8.0% [3], [4], [5]. Population-based studies have shown that prevalence of PN increases with age [5], being a common cause of chronic pain in the elderly [6].

An association between PN and Parkinson's disease (PD) has been described in some rare genetic forms of PD, such as in patients with PARK2 mutations [7] and has also been linked to levodopa exposure [8].

The aim of this work was systematically to review available studies on PN in idiopathic Parkinson's disease (IPD) in an attempt to clarify causal mechanisms of peripheral nervous system involvement in IPD.

Section snippets

Literature search strategy

A systematic computer-based literature search was conducted on April 9th, 2017 using the PubMed database. For the search we used two Medical Subject Headings (MeSH) terms in title or abstract. Term A was “Parkinson” or “Parkinson's” and Term B was “neuropathy” OR “polyneuropathy”. Limitations included human species, English language and full text available. We also perused the reference lists of the papers in order to find papers not identified through the search strategy.

Inclusion and exclusion criteria

To be included in the

Search results

This search strategy resulted in the identification of 278 articles. After the eligibility assessment, 243 articles were excluded and 35 met the inclusion criteria. Scanning the reference lists 3 more papers were identified. In total, 38 papers were used for this review. Table 1 summarizes the characteristics of these papers (full details for each study are available as an online Supplement). Fig. 1 illustrates the study selection process.

Epidemiology of large fiber neuropathy

Large fiber neuropathy occurs when the Aα and Aβ

Conclusion

The pooled estimate of the prevalence of large fiber neuropathy in idiopathic PD is estimated to be 16.3%. This is significantly higher compared to the prevalence of PN in the general population. However, this figure should be interpreted with caution, given the heterogeneity of the study populations and the fact that in some studies patients with risk factors such as diabetes and excessive alcohol consumption were excluded. Therefore, the prevalence of PN in PD might be even greater. In

Disclosures

Nothing to disclose.

Conflict of interest

None.

Author contributions

PZ and KRC have conceptualized the review. PZ carried out the systematic literature review and wrote the manuscript. RAG, KRC, and MH revised the manuscript.

The following is the supplementary data related to this article.

. Characteristics of the studies that were included in this review.

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