What causes peripheral neuropathy?

Causes of Peripheral Neuropathy

Peripheral neuropathy has multiple etiologies, with diabetes being the most common cause, accounting for approximately 50% of all cases. 1

Major Causes of Peripheral Neuropathy

Metabolic and Endocrine Causes

• Diabetes mellitus: The leading cause of peripheral neuropathy 2
  • Poor glycemic management is strongly associated with development and progression
  • In type 1 diabetes, optimizing glucose control can prevent development
  • In type 2 diabetes, glucose control can slow progression
• Prediabetes and metabolic syndrome: Increasingly recognized as significant risk factors 1
• Hypothyroidism: Common treatable cause 3

Nutritional Deficiencies

• Vitamin B deficiencies:
  • Vitamin B6 (pyridoxine) deficiency: Causes axonal degeneration and motor neuron dysfunction 2
  • Vitamin B12 deficiency: Common treatable cause 3, 4
• Other nutritional deficiencies: Can lead to various forms of neuropathy 4

Toxic Exposures

• Medications:
  • Chemotherapy agents (particularly taxanes and oxaliplatin) 2
  • Isoniazid (antituberculosis medication) 2
  • Various prescription medications 4
• Alcohol use: Common cause of toxic neuropathy 3, 5
• Environmental and occupational toxins 4

Immune-Mediated Causes

• Guillain-Barré syndrome: Acute inflammatory demyelinating polyneuropathy 6
• Chronic inflammatory demyelinating polyneuropathy (CIDP) 6

Other Causes

• Nerve compression or injury: Including carpal tunnel syndrome (most common mononeuropathy) 5, 6
• Hereditary diseases: Various genetic disorders affecting peripheral nerves 5
• Idiopathic: No identifiable cause in 25-46% of cases 5

Clinical Presentation and Diagnosis

Common Symptoms

• Numbness and paresthesia (tingling, burning sensations)
• Sensory loss in a "stocking and glove" distribution
• Pain (may be burning, shooting, or stabbing)
• Progressive weakness and atrophy in later stages 5

Diagnostic Approach

1. Neurological examination: Assessment for loss of protective sensation (LOPS) using:

   • 10-g monofilament test (most sensitive)
   • Additional tests: pinprick, temperature perception, vibration with 128-Hz tuning fork, ankle reflexes 2

2. Laboratory testing:

   • Complete blood count
   • Comprehensive metabolic profile
   • Fasting blood glucose
   • Vitamin B12 levels
   • Thyroid-stimulating hormone levels
   • Erythrocyte sedimentation rate
   • Serum protein electrophoresis with immunofixation 3, 5

3. Specialized testing when indicated:

   • Electrodiagnostic studies (nerve conduction studies and electromyography)
   • Nerve biopsy in unclear cases 3

Risk Factors and Prevention

Risk Factors

• Age (higher prevalence in those >50 years)
• Male gender (except for carpal tunnel syndrome)
• Diabetes duration and poor glycemic control
• Obesity and metabolic syndrome
• Smoking
• Retinopathy and nephropathy 2, 6

Prevention Strategies

• Optimal glycemic control in diabetes
• Regular foot examinations in high-risk patients
• Lifestyle modifications including weight loss and exercise
• Avoiding toxic exposures including excessive alcohol 2, 1

Important Considerations

• Peripheral neuropathy prevalence increases with age, affecting up to 7% of those over 65 years 6
• Early recognition and treatment of underlying causes can prevent progression
• In diabetic patients, comprehensive foot examinations should be performed annually or more frequently in high-risk individuals 2
• Lifestyle-based treatments combining dietary counseling with exercise may be beneficial for neuropathy associated with type 2 diabetes, prediabetes, and metabolic syndrome 1

Understanding the specific cause of peripheral neuropathy is crucial for appropriate management, as many forms have specific treatments that can improve symptoms or halt progression.