What are the causes of polyneuropathy?

Causes of Polyneuropathy: A Comprehensive Classification

Yes, your classification of polyneuropathy causes is accurate and comprehensive, covering the major etiologies that clinicians should consider when evaluating patients with polyneuropathy.

Metabolic Causes

• Diabetes mellitus is indeed the most common cause of polyneuropathy in Europe and North America 1
• Vitamin B12 deficiency is a significant cause, with 2.2-8% of polyneuropathy patients showing evidence of B12 deficiency 2
• Other nutritional deficiencies (vitamin B1, B6, folate, vitamin E) can cause polyneuropathy and should be considered in the diagnostic workup 2
• Hypoglycemia, hypothyroidism, chronic kidney disease (CKD), and mitochondrial disorders are correctly included as metabolic causes 2

Inflammatory/Immune-Mediated Causes

• Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and vasculitic neuropathies are important inflammatory causes 2
• Sarcoidosis can present with polyneuropathy as listed in your classification 2

Malignancy-Related Causes

• Paraneoplastic syndromes can cause polyneuropathy and should be considered, particularly in patients with unexplained neuropathy 2
• Polycythemia rubra vera is correctly included as a potential cause 2

Infectious Causes

• Leprosy, HIV, syphilis, and Lyme disease are all established infectious causes of polyneuropathy 2

Toxins/Drug-Induced Causes

• Alcohol-associated polyneuropathy has a prevalence of 22-66% among persons with chronic alcoholism 1
• Chemotherapy-induced neuropathies (CIN) have gained clinical importance with a prevalence of 30-40%, varying by drug and regimen 1
• Lead and arsenic toxicity are correctly included as causes of toxic polyneuropathy 2

Hereditary Causes

• Charcot-Marie-Tooth disease, Refsum's syndrome, and adrenoleukodystrophy are correctly listed as hereditary causes 2
• Genetic testing is established as useful for accurate diagnosis of hereditary neuropathies 2

Other Causes

• Amyloidosis and paraproteinemias (monoclonal gammopathies) are important causes to consider 2
• Monoclonal gammopathies are more common in polyneuropathy patients than in the general population, with approximately 10% of patients with polyneuropathy of unknown etiology having monoclonal gammopathy 2

Idiopathic Polyneuropathy

• Your statement that 20-25% of chronic polyneuropathies have no identifiable cause is accurate 2

Diagnostic Approach

• Screening laboratory tests with the highest yield include blood glucose, serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis 2
• When routine blood glucose testing is normal, testing for impaired glucose tolerance should be considered, especially in patients with painful sensory polyneuropathy 2, 3
• Electrodiagnostic studies are essential to confirm diagnosis and distinguish between axonal and demyelinating patterns 3

Clinical Pearls

• Up to 50% of diabetic peripheral neuropathy may be asymptomatic but still increases risk for complications 4
• In patients with B12 levels in the low-normal range (200-500 pg/dL), 5-10% may still have B12 deficiency as indicated by elevated metabolites 2
• Serum protein immunofixation electrophoresis (IFE) is more sensitive than serum protein electrophoresis (SPEP) for detecting monoclonal gammopathies 2

Your classification provides an excellent framework for approaching the differential diagnosis of polyneuropathy in clinical practice.