Vasculitic Neuropathy Workup

• Laboratory studies are more helpful in systemic than nonsystemic vasculitis; however, obtain the following studies in any patient in whom vasculitic neuropathy is suspected. In general, place the results in the context of the clinical presentation for a diagnosis. For those individuals with multiple high levels of the inflammatory markers listed here, consultation with a rheumatologist is strongly recommended.
• Nonsystemic vasculitic neuropathy has a better prognosis than systemic vasculitic neuropathy. The former may have normal laboratory results, while systemic vasculitis often features elevated antinuclear antibody (ANA) titers, erythrocyte sedimentation rate (ESR), and other more specific markers of disease.

  • ESR (high, after age adjusted) - More than 70% of patients show ESR >20 mm/h
  • Antinuclear antibody titer (high in systemic diseases associated with vasculitic neuropathy)
  • Extractable nuclear antigens, p-ANCA and c-ANCA
  • Rheumatoid factor
  • Antineutrophil cytoplasmic antibodies
  • Hepatic enzymes
  • Renal function tests
  • Serum complement
  • Serum immunoelectrophoresis (or immunofixation) and quantitative immunoglobulins
  • Cryoglobulins
  • Hepatitis B antigen and antibody
  • Hepatitis C antigen
• Routine cell count and serum electrolytes are indicated. Anemia is present in up to 30% of patients.
• Serum analysis for other common causes of neuropathy, including hemoglobin A1c (HbA1c) and fasting glucose to rule out diabetes, thyroid function tests, B-12 and folate, and rapid plasma reagent (RPR).
• CSF analysis can show high protein levels (>50 mg) in a small percentage of patients.

• Brain imaging studies are usually not necessary, and a central nervous system etiology can be excluded comfortably by an accurate neurologic examination.
• Magnetic resonance imaging (MRI) of the spine can be helpful in excluding a spinal nerve root lesion when suggested.

• Nerve conduction studies and electromyography

  • Electrodiagnostic testing is essential in making the diagnosis of any neuropathy, especially in vasculitic neuropathy. Electrodiagnostic testing can help accurately define the pathophysiology and localize the extent and distribution of the neuropathy. It also can provide information on whether the disease is active in the form of signs of active denervation, which accordingly facilitates choice of treatment protocol.
  • The predominant electrophysiologic feature of vasculitic mononeuropathy multiplex is axonal loss. "Conduction block" in vasculitic mononeuropathy multiplex is secondary to focal axonal conduction failure, presumably related to infarct of the axon.
  • Needle electromyography can demonstrate denervation potentials. Presence of positive sharp waves and fibrillation potentials indicates active denervation. Amplitude and duration of motor units assess the duration of axon loss and the presence of reinnervation changes. Recruitment pattern identifies the amount of functional axonal loss.

• Nerve and muscle biopsy

  • Tissue diagnosis is the criterion standard in making the diagnosis of vasculitic neuropathy and is recommended in the presence of any doubtful clinical picture or if ultimate diagnosis is required.
  • Biopsy may not be necessary if the clinical presentation of multifocal neuropathy is confirmed by electrodiagnostic testing and other systemic signs of vasculitis are present. Many academic institutions perform biopsy initially.
  • Sural nerve, superficial peroneal nerve, and muscle tissues (peroneus brevis) are most suitable for biopsy.
• Blood vessels are infiltrated by inflammatory cells with signs of vascular injury including endothelial cell disruption, fragmentation of the internal elastic lamina, and fibrinoid necrosis with hemorrhage or thrombus; these findings are seen in definitive cases of nerve biopsy.

The diagnosis of peripheral nerve involvement may be established by nerve and muscle biopsies; these tissues typically exhibit inflammatory cell infiltrates and fibrinoid necrosis of the walls of blood vessels. However, the biopsy specimen may demonstrate only axonal degeneration if vasculitis has caused a nerve infarct that is proximal to the site of biopsy or if no affected vessels are encountered in the specimen.

Immunohistochemical evaluation of sural nerve biopsy specimens may be helpful in identifying patients with microvasculitis.

Pathologic features associated with necrotizing vasculitis include muscle fiber necrosis and/or regeneration, predominant axonal nerve pathology, wallerian-like degeneration, and asymmetric nerve fiber loss.