What are the causes of neuropathy?

Causes of Neuropathy

Diabetes is the most common cause of peripheral neuropathy, accounting for approximately half of all cases, but numerous other etiologies must be considered when evaluating patients with neuropathic symptoms. 1

Common Causes of Neuropathy

Metabolic Causes

• Diabetes mellitus: The leading cause of peripheral neuropathy worldwide 1, 2

  • Affects up to 50% of all diabetic patients with long duration of disease 2
  • Can present as distal symmetric polyneuropathy (most common), mononeuropathy, or autonomic neuropathy 2

• Prediabetes/Impaired glucose tolerance: Found in approximately 40% of patients with idiopathic neuropathy 3

  • Causes preferential injury to small nerve fibers resulting in pain and autonomic dysfunction

• Hypothyroidism: A common treatable cause of neuropathy 4, 5

• Uremia/Chronic kidney disease: Can cause neurotoxic metabolite accumulation 5, 6

Nutritional Deficiencies

• Vitamin B12 deficiency: Critical to evaluate in all neuropathy patients 5, 4
• Other vitamin deficiencies: Including B1 (thiamine), B6, and vitamin E 5

Toxic Causes

• Alcohol abuse: Direct neurotoxic effect and nutritional deficiencies 6, 5
• Medications: Particularly chemotherapy agents (neurotoxic) 2, 5
• Environmental toxins: Including heavy metals and industrial chemicals 6, 5

Immune-Mediated Causes

• Chronic inflammatory demyelinating polyneuropathy (CIDP) 2, 5
• Vasculitis: Can cause mononeuritis multiplex 5
• Guillain-Barré syndrome: Acute inflammatory demyelinating polyneuropathy 4

Infectious Causes

• HIV-associated neuropathy 2, 5
• Lyme disease
• Leprosy

Malignancy-Related

• Multiple myeloma: Can cause paraproteinemic neuropathy 2, 5
• Paraneoplastic neuropathy: Associated with bronchogenic carcinoma and other cancers 2, 5

Hereditary Causes

• Inherited neuropathies: Such as Charcot-Marie-Tooth disease 2, 5

Mechanical/Compressive

• Cervical and lumbar disease: Including nerve root compression, spinal stenosis 2
• Entrapment neuropathies: Such as carpal tunnel syndrome 2

Diagnostic Approach

Initial laboratory evaluation for neuropathy should include:

• Complete blood count
• Comprehensive metabolic profile
• Fasting blood glucose and HbA1c
• Vitamin B12 level
• Thyroid-stimulating hormone level
• Erythrocyte sedimentation rate 4, 5

Additional specialized tests based on clinical suspicion:

• Serum protein electrophoresis (for paraproteinemia)
• HIV testing
• Vasculitis panel
• Lumbar puncture (for Guillain-Barré syndrome or CIDP) 4

Electrodiagnostic studies (nerve conduction studies and electromyography) help differentiate between axonal and demyelinating neuropathies 4, 5

Clinical Pearls

1. Always consider non-diabetic causes of neuropathy even in patients with known diabetes 2, 5

2. The diagnostic flowchart for distal symmetric polyneuropathy should include assessment of:

   • Temperature sensation
   • Pinprick sensation
   • Vibration perception
   • Pressure sensation
   • Ankle reflexes 2

3. Be aware of "insulin neuritis" or "treatment-induced neuropathy," which can occur with rapid glycemic control 5

4. Metabolic syndrome components (obesity, dyslipidemia) may contribute to neuropathy risk even before diabetes develops 1, 3

5. For diabetic patients, a complete neurologic evaluation should be performed at diagnosis for type 2 diabetes or 5 years after diagnosis for type 1 diabetes, with annual follow-up thereafter 2

Understanding the diverse causes of neuropathy is essential for proper diagnosis and management, as treatment should address the underlying etiology whenever possible.