What is the etiology of peripheral neuropathy?

From the Guidelines

Neuropathy is caused by various factors that damage peripheral nerves, with diabetes mellitus being a major cause, as highlighted in the most recent study 1. The etiology of peripheral neuropathy is complex and multifactorial. According to the latest evidence 1, diabetic neuropathies are a heterogeneous group of disorders with diverse clinical manifestations. The most common causes of peripheral neuropathy include:

• Diabetes mellitus (diabetic neuropathy)
• Alcohol abuse
• Vitamin deficiencies (particularly B1, B6, B12, and E)
• Autoimmune disorders like Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy
• Infections such as HIV, Lyme disease, and leprosy
• Medications (especially chemotherapy drugs like vincristine, cisplatin, and paclitaxel)
• Toxin exposure (lead, mercury, arsenic)
• Kidney disease
• Liver disease
• Certain cancers (particularly those causing paraneoplastic syndromes)
• Hereditary conditions like Charcot-Marie-Tooth disease
• Trauma
• Compression (carpal tunnel syndrome, radiculopathy)
• Vascular disorders affecting blood supply to nerves

As noted in 1, diabetic neuropathy is a diagnosis of exclusion, and non-diabetic neuropathies may be present in people with diabetes and may be treatable. It is essential to identify the specific cause of neuropathy, as addressing the underlying etiology can sometimes halt or reverse nerve damage, particularly in toxic, nutritional, or medication-induced neuropathies. The pathophysiological mechanisms underlying neuropathy include oxidative stress, inflammation, and mitochondrial dysfunction, as mentioned in 1.

In clinical practice, it is crucial to consider all possible causes of neuropathy, as highlighted in 1, and to use simple clinical tests to assess small- and large-fiber function and protective sensation. Electrophysiological testing or referral to a neurologist may be necessary in situations where the clinical features are atypical or the diagnosis is unclear. The most recent study 1 emphasizes the importance of early recognition and appropriate management of neuropathy in people with diabetes to improve symptoms, reduce sequelae, and improve quality of life.

From the Research

Etiology of Peripheral Neuropathy

The etiology of peripheral neuropathy is complex and multifaceted, with various underlying causes and risk factors. Some of the most common causes include:

• Metabolic disorders, such as diabetes mellitus, which is the most common cause of polyneuropathy in Europe and North America 2
• Impaired glucose metabolism, including diabetes and prediabetes, which accounts for approximately 25% of cases 3
• Dysimmune neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) 4
• Vitamin deficiencies, including vitamin B12 deficiency, which is a common cause of chronic neuropathies 4
• Toxic substances and drugs, such as chemotherapy-induced neuropathies (CIN) 2
• Genetic causes, such as hereditary neuropathies 2
• Immunological processes, such as autoimmune diseases and paraproteinemic neuropathies 4

Risk Factors and Predisposing Conditions

Certain risk factors and predisposing conditions can increase the likelihood of developing peripheral neuropathy, including:

• Prolonged exposure to high blood glucose levels, which can damage nerve fibers 5
• Chronic alcoholism, which can lead to alcohol-associated polyneuropathy 2
• Malignant disease and chemotherapy, which can cause chemotherapy-induced neuropathies (CIN) 2
• Advanced age, which can increase the risk of developing polyneuropathy 2

Diagnostic Evaluation

A thorough diagnostic evaluation is essential to identify the underlying cause of peripheral neuropathy, including:

• Clinical history and physical examination results 6
• Laboratory and electrodiagnostic tests, such as skin biopsy and blood testing 6, 3, 4
• Screening for treatable causes, such as dysimmune neuropathies and celiac disease 4