The term “peripheral neuropathy” (PN) refers to disorder of the peripheral nervous system. Robust epidemiological data on polyneuropathies of any cause are lacking. Very few studies have accurately assessed the prevalence of polyneuropathy. When confirmed with nerve conduction studies, the prevalence of polyneuropathy is estimated to be about 5% in people aged 55 years or more [
Classification of PN depends upon a mixture of phenomenological, neurophysiological, pathological, and aetiological parameters [
Neuropathic pain is prevalent, presenting in approximately two-thirds of patients with PN [
The aim of this study was to systematically review the current literature regarding QoL in patients with painful PN. We aimed to evaluate any variations in QoL between the different PN subtypes and more specifically clarify what is the direct effect of pain in patients’ QoL. The effect of the various treatments on the overall QoL is also discussed. To our knowledge, this is the first systematic review on the topic.
A systematic computer-based literature search was conducted on 11 December, 2018, using the PubMed database. We evaluated all articles published between the dates of 1 January 1998 and 11 December 2018. For the search, we used three Medical Subject Headings (MeSH) terms that had to be present in the title or the abstract. Term A was “quality of life” or “qol.” Term B was “pain” or “painful.” Term C was “neuropathy” or “polyneuropathy” or “ganglionopathy” or “neuronopathy.” “Human species,” “English language,” and “full-text available” filters were applied in our search.
In order to be included in this review, articles were required to meet the following criteria: [
This study is reported in accordance with the “Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines” [
This article is based upon previously published studies. The article is in compliance with the journal’s ethical guidelines.
The PubMed search identified 477 articles, and a total of 412 articles were excluded during the eligibility assessment. A further article was added after scanning the references of the included studies. The PRISMA chart displays the process of article selection (Figure
PRISMA chart.
Characteristics of the papers included in the review.
Total number of papers included in this review | 66 |
|
|
Type of paper (%) | |
Case series | 30 (45.5) |
Case-controlled study | 7 (10.6) |
Randomised controlled trial | 29 (43.9) |
Mean number of patients with painful neuropathy, per paper (SD) | 125.1 (122.5) |
Male to female ratio | 1 : 1 |
|
|
Aetiology of polyneuropathy, number of papers (%) | |
Chronic idiopathic axonal | 2 (3.0) |
Chemotherapy-induced | 4 (6.1) |
Diabetic | 47 (71.2) |
Genetic | 1 (1.5) |
Gluten | 1 (1.5) |
HIV | 3 (4.5) |
Immune-mediated | 1 (1.5) |
Multiple aetiologies | 6 (9.1) |
Sarcoidosis | 1 (1.5) |
|
|
Number of publications per decade | |
Until 2000 | 3 (4.5) |
2000–2009 | 16 (24.2) |
2010–2018 | 47 (71.2) |
In total, 19 different tools were used to assess QoL in PN patients. The most commonly utilised tools were the SF-36 (34.8%) and the EQ-5D (22.7%), both of which are generic health status measurements. A number of disease-specific questionnaires were employed, such as the NeuroQol (6.1%), a specifically validated neuropathy and foot ulcer instrument [
Questionnaires used to assess quality of life.
Questionnaire |
|
---|---|
Brief Pain Inventory | 7 (10.6) |
Child Health Questionnaire | 1 (1.5) |
Diabetic peripheral neuropathic pain impact measure | 1 (1.5) |
EQ-5D | 15 (22.7) |
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (fact/GOG-ntx) Questionnaire | 1 (1.5) |
Medical Outcomes Study HIV Health Survey | 1 (1.5) |
Neuropathic Pain Impact on Quality of Life (NePIQoL) Questionnaire | 1 (1.5) |
NeuroQoL | 4 (6.1) |
Norfolk Quality of Life Questionnaire-DN | 4 (6.1) |
Nottingham Health Profile | 1 (1.5) |
PART-Q30 | 1 (1.5) |
QLQ-C30 | 2 (3.0) |
QLQ-CIPN20 | 1 (1.5) |
Quality of life index | 1 (1.5) |
Questionnaire not specified/unvalidated | 6 (9.1) |
SF-12 | 2 (3.0) |
SF-36 | 23 (34.8) |
Sheehan disability score | 2 (3.0) |
World Health Organization Biomedical Research and Education Foundation quality of life score | 1 (1.5) |
A selection of studies examined aetiologically heterogeneous populations of patients with PN. The disability caused by PN has been shown to correlate with a decrease in QoL, and it has been demonstrated that painful PN is associated with a poorer QoL compared to painless PN, regardless of the cause [
QoL is one of the most important aspects of patients’ lives affected by diabetes, both due to its effect on the long-term prognosis and on the economic burden of the disease.
Depression and anxiety also have an impact on perceived QoL. Depressed patients may report lower QoL at baseline in clinical trials and subsequently negative treatment effects [
Lacosamide has a long-term safety profile and sustained efficacy in PDN. Apart from treating pain, use of lacosamide leads to improvements in the “physical functioning” and “vitality” subdomains of the SF-36 [
Gabapentin has proven to be an effective pain relief and has demonstrated additional benefits in improving patients sleep quality and mood [
Amitriptyline and nortriptyline were found to have equal tolerability and efficacy in painful DPN both as monotherapy and as adjuvant therapies; however, no statistically significant changes were noted in overall QoL [
One, small, randomised controlled trial evaluated the application of topical
A double-blind randomised controlled trial found that topical nutmeg extracts reduce pain in painful DPN and improve overall QoL after 4 weeks of treatment; however, these effects were not superior to placebo [
The effects of alpha-lipoic acid were found to have a clinically significant impact on controlling neuropathic pain and improving overall QoL in a cohort of patients taking this agent orally [
Spinal cord stimulation (SCS) is an invasive treatment for chronic pain, based on electrical stimulation of the dorsal columns [
Low-frequency pulsed magnetic field magnetostimulation showed no advantage over sham exposure in reducing pain intensity, decreasing sleep disturbance, or improving QoL [
Findings from a randomised, double-blind, placebo controlled trial suggest that the administration of photon stimulation resulted in significant improvements in sensation, social functioning, and mental health; however, further studies are needed to investigate different doses and durations of treatment [
Although rarely addressed in the literature, wearing static, permanent magnetic insoles produces a significant reduction in pain, either as an adjunctive or monotherapy [
Aromatherapy massage has been found to be a safe, effective, low-risk treatment option with high compliance rates, with both pain and QoL scores significantly improving after 4 weeks of treatment [
Peripheral neuropathy is a common extraintestinal manifestation of serologically confirmed gluten sensitivity (positive gliadin antibodies and/or tissue transglutaminase or endomysium antibodies) [
Anti-myelin associated glycoprotein antibody (anti-MAG) neuropathy is a type of immune-mediated neuropathy. Rajabally et al. showed that presence of pain has a significant impact on QoL. This study brings new insights on the practical management of patients with anti-MAG neuropathy, in indicating that neuropathic pain and pain related to cramps play a significant role in the impairment of function and the overall QoL in affected patients [
Many chemotherapy treatments induce peripheral neuropathy (CIPN), and it is a persistent problem beyond treatment [
Duloxetine has been tried as a treatment of painful CIPN in 2 studies [
Opioids such as tapentadol have also been used in the treatment of CIPN. Galie et al. found QoL scores were significantly improved after treatment, thus proving a correlation between treating pain and subsequently QoL [
HIV-related polyneuropathy is prevalent in HIV patients; however, the exact cause is unknown. Hypothesized mechanisms include altered immunity, nutritional factors, infectious processes and as a result of the adverse effects of highly active antiretroviral therapy causing damage to the peripheral nervous system [
Regarding pharmacological therapies, although capsaicin is effective in treating pain associated with HIV-associated PN, it has not shown a significant improvement of the overall QoL [
Nonpharmacological therapies include hypnosis, which has not only shown reduction in pain intensity but an improvement in QoL and a reduction in depression-related symptoms [
Moreover, Knezevic et al. presented the first reports of spinal cord stimulation in two patients refractory to conservative treatments [
Only one study in our review evaluated the effect of painful Charcot–Marie–Tooth (CMT) disease (mainly CMT1 and CMT2) on QoL in a paediatric population and found pain negatively affects QoL [
PN is a common occurrence in haemodialysis patients and has been related to an impaired QoL. Reduced QoL is independently related to worse clinical outcomes and increased mortality in haemodialysis patients [
Sarcoidosis is an inflammatory disease affecting many tissues, including dysfunction of small nerve fibres, the prevalence of which is grossly underestimated [
Chronic Idiopathic axonal polyneuropathy (CIAP) is a term describing neuropathies with sensory and motor involvement, in a length-dependant distribution. It is slowly progressive, insidious, with no identifiable aetiology despite extensive diagnostic work-up [
This systematic review has identified the following key points: Pain has an additional negative impact on QoL in patients with PN, regardless of the aetiology of their neuropathy. The treatment of neuropathic pain is universally the same, and current guidelines for the treatment exist [ It has been highlighted that specific diets (based on the aetiology of the neuropathy) can play an additional role in improving QoL, for example, diet control in diabetes and a gluten-free diet in gluten neuropathy. This systematic review has highlighted that only one paper focuses on a paediatric population, where the cause of the neuropathy was CMT. In order to better understand the QoL in adult populations, further assessment of genetic neuropathies should be studied using a variety of population ages. It is likely that patients with PN suffer from comorbidities that are affecting the QoL independently to the burden caused by the painful peripheral neuropathy. Comparing the QoL of groups of patients with PN of different aetiologies using multivariate statistics can eliminate this risk of bias. The majority of the tools for evaluating QoL that were used in the papers included in this review were generic (i.e., SF-36). Designing and validating tools for evaluating QoL in patients with PN are important. Such tools should capture and weigh accordingly specific to PN domains that might be affected.
The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.
The authors declare that they have no conflicts of interest.
This is a summary of independent research carried out at the NIHR Sheffield Biomedical Research Centre (Translational Neuroscience).