What is mononeuritis multiplex?

Mononeuritis Multiplex

Mononeuritis multiplex is a peripheral nerve disorder characterized by asymmetric damage to multiple noncontiguous peripheral nerve trunks, resulting in motor, sensory, or mixed deficits in the distribution of the affected nerves. It is typically caused by underlying systemic conditions, most commonly vasculitis, and requires prompt diagnosis and treatment to prevent permanent neurological damage.

Clinical Presentation

• Asymmetric presentation: Affects multiple individual nerves in a random, asymmetric pattern
• Sensory symptoms: Pain, paresthesias, numbness in distribution of affected nerves
• Motor symptoms: Weakness, atrophy in muscles innervated by affected nerves
• Progression: Can evolve rapidly or gradually depending on underlying cause
• Distribution: May involve any peripheral nerve, including cranial nerves

Diagnostic Approach

Electrodiagnostic Studies

• Nerve conduction studies and electromyography are essential to:
  • Identify affected nerves
  • Differentiate mononeuritis multiplex from polyneuropathy
  • Distinguish axonal from demyelinating patterns 1, 2

Laboratory Testing

• Complete autoimmune workup:
  • ANCA antibodies (for vasculitis)
  • Antinuclear antibodies (ANA)
  • Anti-DNA antibodies
  • Cryoglobulins
  • Hepatitis serology 2

Biopsy

• Combined nerve and muscle biopsy is recommended over nerve biopsy alone 2
• Sural nerve is commonly biopsied to establish diagnosis and identify underlying cause
• May show vasculitis, granulomatous inflammation, or other pathological processes 3, 4

Common Underlying Causes

1. Vasculitis

   • ANCA-associated vasculitis
   • Polyarteritis nodosa
   • Granulomatosis with polyangiitis

2. Systemic autoimmune diseases

   • Systemic lupus erythematosus (occurs in 2-3% of patients) 1
   • Rheumatoid arthritis
   • Sarcoidosis 3

3. Infections

   • Hepatitis E virus 1
   • Hepatitis C virus 1
   • HIV
   • Lyme disease

4. Metabolic/endocrine disorders

   • Diabetes mellitus
   • Amyloidosis

5. Other causes

   • Paraneoplastic syndromes
   • Immune checkpoint inhibitor therapy 5
   • Immunoglobulin deficiencies 6

Treatment

First-line Treatment

• For vasculitis-associated mononeuritis multiplex:
  • Combination of glucocorticoids and cyclophosphamide or rituximab 2
  • Intravenous pulses of glucocorticoids followed by high-dose oral glucocorticoids

Second-line/Refractory Cases

• Intravenous immunoglobulin
• Plasma exchange
• Rituximab (if not used first-line)
• TNF-α inhibitors (etanercept, infliximab, adalimumab) for specific causes like sarcoidosis 3

Response Rates

• Treatment with glucocorticoids alone or with immunosuppressive therapy results in favorable response in 60-75% of cases 1, 2
• Delayed treatment (>2 weeks) is associated with worse neurological outcomes 1

Prognosis and Monitoring

• Peripheral neuropathy is a significant predictor of damage in systemic lupus erythematosus 1, 2
• Serial neurological examinations are recommended over repeated electrodiagnostic studies for monitoring disease activity 2
• Physical therapy is recommended for patients with nervous and muscular involvement 2

Special Considerations

• Pediatric mononeuritis multiplex is extremely rare and most commonly associated with autoimmune disorders 7
• Pure sensory forms of mononeuritis multiplex occur rarely 6
• Non-vasculitic forms may still respond to steroid therapy 4

Early diagnosis and prompt initiation of appropriate immunosuppressive therapy are crucial to prevent irreversible nerve damage and improve long-term neurological outcomes in patients with mononeuritis multiplex.