The Global Burden of Polyneuropathy—in Need of an Accurate Assessment

Up to 7% of adults have polyneuropathy symptoms, which can result from metabolic and nutritional disorders, toxins, and autoimmune, infectious, and hereditary causes, among others. Despite this, the global burden of polyneuropathy remains largely unknown. In addition to enumerating mortality, the original Global Burden of Diseases, Injuries, and Risk Factors (GBD) study was designed to quantify disability resulting from nonfatal medical conditions so that they could be objectively prioritized by public health and policymakers. Subsequent rounds of the GBD study have expanded to include neurologic “…conditions for which neurologists play a particular important role in care and diagnosis.”^1(p173) In the US, disorders of the peripheral nervous system, of which polyneuropathy is the most common, account for more than 10% of neurology visits per year.² Yet, the GBD study does not include polyneuropathy. The fact that the GBD study overlooks the burden of polyneuropathy has important consequences for patients, public health, and research.

Patients with polyneuropathy experience substantial morbidity. Nearly half of patients with polyneuropathy experience pain, which manifests as burning, stabbing, and/or electrical sensations that are often disabling and refractory to existing symptomatic treatments. Polyneuropathy can also lead to decreased sensation and weakness in the extremities, which predisposes to difficulty walking, loss of balance, and falls. Amputation owing to foot trauma remains stunningly common, which further affects independence. Individuals with polyneuropathy are nearly 4 times more likely to undergo lower-limb amputation than age- and sex-matched peers without polyneuropathy.³ Further, patients with polyneuropathy have significantly shorter survival than age- and sex-matched controls, even after controlling for comorbidities.³ Intractable pain leads to poor sleep and decreased mobility results in lost activities of daily living, which manifest as worse quality of life and considerable depression that is frequently underaddressed by the health care system. Polyneuropathy significantly affects the lives of patients with few existing interventions to relieve symptoms or prevent progression.

In addition to the morbidity experienced by patients, the burden of polyneuropathy for the health care system is considerable. Polyneuropathy results in greater health care utilization.⁴ In the US, nearly 11 billion dollars per year is spent on the costs and complications of diabetic polyneuropathy.⁵ In Denmark, polyneuropathy is associated with an additional 6999 Euros (approximately $8016 US dollars) of direct health care costs per person per year.⁶ These costs will multiply as the prevalence of polyneuropathy increases, placing substantial burden on available health care resources. Specifically, the prevalence of diabetes, which accounts for 40% of polyneuropathy cases,⁷ is expected to increase 51% to 700 million people in 2045 and is expected to disproportionally affect low- and middle-income countries.⁸ Although the current costs of polyneuropathy are sizable, the future costs will rise dramatically as the prevalence of polyneuropathy and its associated risk factors increase.

The primary metric of the GBD, the disability-adjusted life year (DALY), combines years of life lost (YLL) owing to premature mortality, as determined using vital statistics for cause of death, and years of healthy life lived with disability (YLD), as measured using disease prevalence and a disability weight for each health state, adjusting for comorbidity.⁹ DALYs have been widely adopted by decision makers to compare burden across diseases and populations, whereas YLD is gaining popularity as a standalone measure as the population ages and there is an increasing burden of nonfatal diseases and injuries. As polyneuropathy is largely a nonfatal disease, its burden is best assessed using YLD. Migraine is the clear frontrunner of YLD among neurologic disorders with 47 million.⁹ The 2018 GBD study round, which included polyneuropathy as a sequela of type 1 and type 2 diabetes, found that diabetes-related polyneuropathy accounts for 25.6 million YLD worldwide.⁹ If diabetic polyneuropathy were included in the 2019 GBD study round, it would rank between the eighth and ninth leading causes of YLD (eighth: anxiety disorders, 27.9 million; ninth: neck pain, 21.0 million YLD).^9,10 However, as diabetes accounts for less than half of polyneuropathy cases, this underestimates the actual burden of polyneuropathy. Polyneuropathy likely causes more than 33 million YLD worldwide. Polyneuropathy has been largely overlooked as a cause of disease by the medical and public health community, and this omission is a missed opportunity to highlight a source of substantial suffering experienced by neurology patients worldwide.

Prior GBD study rounds have highlighted the unmet physical and psychosocial needs of patients with neurologic disorders and have bolstered calls to improve access to neurologic services and research. It is widely accepted that the burden of polyneuropathy will continue to grow as the population ages, further exacerbating disparities in access to neurologic care within the US and between high-, low-, and middle-income countries. Three main harms result from the lack of an accurate assessment of polyneuropathy burden. First, clinicians need to be aware of the burden of polyneuropathy, so that they spend appropriate time evaluating for symptoms and examining patients for this prevalent condition. Currently, less than one-third of physicians recognize manifestations of diabetic polyneuropathy, even when the patient is symptomatic.⁸ Further, an insufficient number of clinicians comprehensively manage and treat patients with polyneuropathy, which increases the risk for complications and amputation by up to 85%.⁸ Training for existing personnel, both general practitioners and specialists, is needed to improve polyneuropathy identification, symptom control, and reduce the risk of infections and falls. In addition, capacity-building to increase the number of available personnel to address the needs of patients with polyneuropathy is warranted. Second, education of public health workers and policymakers regarding the burden of polyneuropathy and its modifiable risk factors, such as metabolic syndrome components, vitamin deficiencies, and alcohol use, is needed. This is essential to provide the appropriate resources to address polyneuropathy and its risk factors in a health care system with finite resources. Third, further research into polyneuropathy causes and treatments in different populations is vital. Research agencies need to make difficult funding decisions that are in part based on disease burden. In the absence of systematic data regarding the burden of polyneuropathy, there is little to guide funders and, as a result, this condition is being neglected. According to the National Institutes of Health (NIH) RePORT Expenditures and Results (RePORTER) website (http://reporter.nih.gov), NIH funding for peripheral neuropathy is estimated at $220 million for 2022. By comparison, Alzheimer disease and related dementias have an estimated NIH funding of $3.2 billion and epilepsy of $212 million, both of which have been included in the GBD study since 1990. Although YLD is only one measure of disease burden, both conditions lead to fewer YLD than polyneuropathy, which emphasizes the dire need to increase polyneuropathy funding. Only then will neurologists be able to address the urgent needs of their patients with polyneuropathy for improved symptomatic treatments and disease-modifying therapies.

Including polyneuropathy in the GBD study is an attainable goal that would greatly improve our ability to characterize current and future patients’ health care needs. Now is the time to respond to this growing health care challenge with an accurate count of global polyneuropathy burden from all causes by including it as a standalone condition in the GBD study. This is critical to ensure there is appropriate funding and a trained workforce available to address the growing burden of polyneuropathy-associated disability and improve quality of life.