What are the different causes of peripheral neuropathy?

Causes of Peripheral Neuropathy

Peripheral neuropathy has numerous causes, with diabetes mellitus being the most common cause in developed countries, followed by metabolic, toxic, inflammatory, and hereditary etiologies. 1, 2

Major Categories of Peripheral Neuropathy

1. Metabolic Causes

• Diabetes mellitus: Most common cause in developed countries 1, 2

  • Presents as distal symmetric polyneuropathy
  • Often sensory or sensorimotor with burning pain, electrical shock sensations, and paresthesias 3
  • Symptoms typically worse at night, causing sleep disturbance 3

• Endocrine disorders:

  • Hypothyroidism 4
  • Uremia (renal insufficiency) 2, 5

• Nutritional deficiencies:

  • Vitamin B12 deficiency 4, 6
  • Thiamine (B1) deficiency 6
  • Vitamin E deficiency 6
  • Folate deficiency 6
  • Copper deficiency 6

• Lipid metabolism disorders 2, 5

2. Toxic Causes

• Medications:

  • Chemotherapeutic agents (most common medication cause) 6, 5
  • Metronidazole 3
  • Anti-TNF agents 3

• Substance abuse:

  • Alcohol 2, 5

• Environmental toxins:

  • Heavy metals 5
  • Industrial chemicals 6

3. Inflammatory/Immune-Mediated Causes

• Autoimmune disorders:

  • Guillain-Barré syndrome 3, 5
  • Chronic inflammatory demyelinating polyneuropathy 3, 5
  • Vasculitis 5

• Infectious diseases:

  • Hepatitis C virus (HCV) 3
    • Can cause sensory, motor, or sensorimotor mono/polyneuropathies
    • Small fiber sensory polyneuropathy
    • Autonomic neuropathy
  • HIV 5
  • Lyme disease 5
  • Leprosy 5

• Inflammatory bowel disease (IBD)-associated:

  • Rare association with peripheral neuropathy 3
  • Can present as demyelinating, small-fiber sensory, large-fiber sensory, or sensorimotor neuropathies 3

4. Hereditary Causes

• Genetic mutations causing hereditary peripheral neuropathies 5
• Amyloidosis 2, 5

5. Compression/Trauma

• Nerve compression or injury 4, 7
• Entrapment neuropathies 3

6. Idiopathic

• No identifiable cause in 25-46% of cases 7

Clinical Presentation Patterns

1. Distal symmetric polyneuropathy:

   • Most common pattern, especially in metabolic causes
   • "Stocking and glove" distribution 7
   • Sensory symptoms (numbness, tingling, burning) often precede motor symptoms 7

2. Mononeuropathy:

   • Affects a single nerve
   • Often due to compression or trauma

3. Mononeuritis multiplex:

   • Multiple individual nerves affected
   • Common in vasculitic and inflammatory causes

4. Autonomic neuropathy:

   • Affects involuntary functions
   • Can include cardiac, gastrointestinal, and urogenital symptoms 3

Diagnostic Approach

1. Clinical assessment:

   • Neurologic testing including thermal sensitivity, pinprick sensation, vibration perception, pressure sensation, and ankle reflexes 3
   • 10-g monofilament test and 128-Hz tuning fork are recommended screening tools 3, 1

2. 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 4, 7

3. Specialized testing when indicated:

   • Electromyography and nerve conduction studies to differentiate axonal from demyelinating neuropathy 4
   • Nerve biopsy in unclear cases 4

Common Pitfalls to Avoid

1. Overlooking non-diabetic causes in patients with diabetes 1
2. Failing to perform comprehensive foot examination in at-risk patients 1
3. Neglecting patient education on preventive measures 1
4. Using opioids as first-line therapy for chronic neuropathic pain 1

Peripheral neuropathy requires a systematic approach to diagnosis, with careful attention to identifying potentially treatable underlying causes. Early recognition and management of the underlying condition can prevent progression and improve outcomes.