What is the diagnostic workup for perineuritis?

Diagnostic Workup for Perineuritis

The comprehensive diagnostic workup for perineuritis should include neurological consultation, MRI imaging, laboratory testing for reversible causes, and consideration of nerve biopsy in cases where diagnosis remains uncertain. 1

Initial Evaluation

• Neurological consultation: Essential for all suspected cases of perineuritis 1
• Clinical assessment: Evaluate for:
  • Sensory-motor deficits (often multifocal and distal-predominant)
  • Pain characteristics (present in most cases)
  • Distribution pattern (legs often more affected than arms)
  • Truncal numbness (present in approximately 30% of cases) 2

Imaging Studies

• MRI of spine with and without contrast: First-line imaging test 1, 3
  • Evaluate for nerve root enhancement/thickening
  • Rule out compressive lesions
  • Cover entire affected region (cervical, thoracic, lumbar as appropriate)
  • Contrast enhancement helps identify inflammatory processes 3
• MRI of brain: Indicated if cranial nerve involvement is suspected 1

Laboratory Testing

• Screen for reversible neuropathy causes: 1

  • Diabetes screening (HbA1c, glucose)
  • Vitamin B12 and folate levels
  • Thyroid function tests (TSH)
  • HIV testing
  • Serum protein electrophoresis
  • Vasculitic and autoimmune screening panels

• Lumbar puncture: 1, 2

  • CSF analysis for:
    • Protein levels (elevated in approximately 55% of cases)
    • Cell count
    • Glucose
    • Cytology (to rule out malignancy)
    • Culture and Gram stain
    • Consider viral PCR testing based on clinical suspicion

Electrophysiological Studies

• Electromyography (EMG) and nerve conduction studies (NCS): 1, 2
  • Evaluate for patterns of:
    • Axonal damage (most common in primary perineuritis)
    • Demyelination
    • Mononeuritis multiplex
    • Polyradiculoneuropathy

Additional Testing Based on Clinical Suspicion

• Serum autoantibody testing: Consider based on clinical presentation 1, 2

  • Antiganglioside antibodies
  • Other autoimmune markers

• Nerve biopsy: Consider in cases where diagnosis remains uncertain 2

  • Typically shows:
    • T-cell predominant inflammation
    • Widening and fibrosis of perineurium
    • Infiltrates in epineurium and/or endoneurium
    • Non-uniform axonal degeneration
    • Sometimes epithelioid cells (may represent PNS-restricted sarcoidosis)

Differential Diagnosis Considerations

Diagnostic workup should also consider potential secondary causes of perineuritis: 2, 4

• Diabetes mellitus (most common association)
• Infectious causes (leprosy, neuroborreliosis)
• Vasculitis
• Neurosarcoidosis
• Neurolymphomatosis
• Autoimmune disorders (IgG4-related disease, granulomatosis with polyangiitis) 5
• Nutritional abnormalities
• Malignancy

Special Considerations

• In cases of optic perineuritis, orbital MRI is essential to evaluate for:

  • Optic nerve sheath enhancement
  • Orbital fat infiltration
  • Extraocular muscle involvement 5

• For suspected immune checkpoint inhibitor-related perineuritis:

  • Follow specific grading and management protocols
  • Consider more aggressive workup for higher grades of symptoms 1

Pitfalls to Avoid

• Do not assume all perineuritis is idiopathic without thorough investigation for underlying causes
• Do not miss potentially treatable conditions (primary perineuritis is typically corticosteroid-responsive) 2
• Avoid misdiagnosing as nonsystemic vasculitic neuropathy without appropriate biopsy evidence
• Do not rely solely on imaging; electrophysiological studies and potentially biopsy are often necessary for definitive diagnosis

The diagnostic approach should be thorough as perineuritis can present with various clinical patterns and may be associated with multiple systemic conditions, with proper diagnosis leading to appropriate treatment and improved outcomes.