What are the causes of peripheral neuropathy?

Causes of Peripheral Neuropathy

Peripheral neuropathy has multiple etiologies, with diabetes being the most common identifiable cause, followed by toxic, metabolic, and nutritional factors. 1

Common Causes

Metabolic and Endocrine Disorders

• Diabetes mellitus is the leading cause of peripheral neuropathy, affecting up to 50% of diabetic patients 1
• Hypothyroidism can cause peripheral nerve dysfunction 2, 3
• Chronic kidney disease with uremic neuropathy 3

Nutritional Deficiencies

• Vitamin B12 deficiency (associated with lowered plasma levels and elevated methylmalonic acid and homocysteine) 4
• Vitamin B1 (thiamine) deficiency 4
• Other B vitamin deficiencies (folate, niacin) 2, 5

Toxic Causes

• Alcohol abuse 2, 3
• Medications:
  • Chemotherapeutic agents (particularly platinum compounds, vincristine) 1, 5
  • Thalidomide and bortezomib (common in multiple myeloma treatment) 1
  • Metronidazole (especially with prolonged use) 1, 5
  • Other neurotoxic medications 1, 5
• Environmental and occupational toxins 5

Immune-Mediated Disorders

• Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy) 6
• Chronic inflammatory demyelinating polyneuropathy (CIDP) 6
• Vasculitis 1
• Autoimmune conditions associated with neuropathies 1

Infectious Causes

• HIV infection 1
• Hepatitis C (often with cryoglobulinemia) 1
• Lyme disease 3

Hematologic and Oncologic Disorders

• Multiple myeloma (both disease-related and treatment-related) 1
• Monoclonal gammopathies 1
• Amyloidosis (light chain deposits) 1
• POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes) 1
• Other malignancies (paraneoplastic neuropathies, direct compression) 1

Hereditary Neuropathies

• Inherited neuropathies (e.g., Charcot-Marie-Tooth disease) 3, 6

Mechanical/Compressive Causes

• Nerve compression syndromes (e.g., carpal tunnel syndrome) 6
• Radicular compression (cervical or lumbar disease) 1

Inflammatory Bowel Disease-Related

• Peripheral neuropathy in IBD patients may be related to nutritional deficiencies, medications, or immune mechanisms 1

Idiopathic Peripheral Neuropathy

• In 25-46% of cases, no specific cause can be identified despite thorough evaluation 3, 6
• Cryptogenic sensory polyneuropathy is more common in older adults 6

Diagnostic Approach

When evaluating peripheral neuropathy, a systematic approach should include:

1. Initial laboratory testing:

   • Complete blood count
   • Comprehensive metabolic profile
   • Fasting blood glucose
   • Vitamin B12 level
   • Thyroid-stimulating hormone level
   • Erythrocyte sedimentation rate
   • Serum protein electrophoresis with immunofixation 2, 3

2. Additional testing based on clinical suspicion:

   • Methylmalonic acid and homocysteine (if B12 deficiency suspected) 4
   • Specialized antibody assays for immune-mediated neuropathies 3
   • Electrodiagnostic studies to differentiate axonal from demyelinating neuropathy 2, 3
   • Lumbar puncture for suspected inflammatory neuropathies 2
   • Nerve biopsy in selected cases 3

Important Clinical Considerations

• Diabetic neuropathy is a diagnosis of exclusion - other causes should always be considered even in patients with diabetes 1
• Up to 50% of diabetic peripheral neuropathy may be asymptomatic 1
• Early symptoms often include sensory alterations (numbness, pain, burning) in a "stocking and glove" distribution 3
• Later stages may involve proximal numbness, distal weakness, or muscle atrophy 3
• Treatment should address the underlying cause when possible 2, 3

Remember that multiple causes may coexist in the same patient, particularly in older adults or those with multiple comorbidities 1, 3.