Serum Antibody Testing and IVIG in Enterovirus Radiculoneuropathy
Serum antibody testing is not routinely indicated for diagnosis or management of enterovirus radiculoneuropathy, but IVIG therapy should be considered in severe cases, particularly in immunosuppressed patients, despite limited evidence from controlled trials.
Diagnostic Approach
Diagnosis relies on CSF PCR for enterovirus detection, not serum antibody testing 1. CSF diagnostic assays are critical to confirming diagnosis and results should be available within 24-48 hours of lumbar puncture 1.
Serum antibody testing has limited utility because:
IVIG Treatment Considerations
When to Consider IVIG
IVIG may be worth considering in patients with severe enterovirus neurological disease, though no randomized trials have been conducted 1. The evidence base is strongest for:
Immunosuppressed patients with enterovirus encephalitis or radiculoneuropathy 2. A systematic review found that immunosuppressed patients are at higher risk of fatal outcomes, and IVIG therapy may confer a survival advantage 2.
Patients with hypogammaglobulinemia and enterovirus CNS infection 2, 3. Even moderate reductions in serum IgG levels predispose to severe enterovirus disease 2.
Severe or progressive neurological disease despite supportive care 1, 4.
Evidence Quality and Limitations
The recommendation for IVIG in enterovirus radiculoneuropathy is Grade C, Level III evidence 1, meaning:
- No placebo-controlled trials exist for enterovirus encephalitis or radiculoneuropathy 1, 2
- Evidence comes primarily from case reports and case series 2
- One prospective trial showed IVIG reduced symptoms in enterovirus aseptic meningitis by approximately 2 days, but this was for meningitis, not encephalitis or radiculoneuropathy 1
Dosing and Administration
When IVIG is used for enterovirus neurological disease:
- Standard dosing: 2 g/kg divided over 2-5 days 1
- Alternative approach: 1-2 g/kg in 2-4 divided doses 1
- Treatment may need to be repeated at monthly intervals for sustained effect 1
- In cases of CNS enterovirus infection with hypogammaglobulinemia, intraventricular immunoglobulin has been used successfully when intravenous administration failed 3
Monitoring During Treatment
- Monitor IgG levels if hypogammaglobulinemia is present 1. Target IgG levels ≥400 mg/dL 1.
- Assess for adverse effects: headache, aseptic meningitis, anaphylaxis (particularly in IgA-deficient patients), and volume overload 1, 5
- Clinical neurological review should occur within 24 hours of referral 1
Alternative and Adjunctive Therapies
Pleconaril (if available) may be considered in severe cases 1. This antiviral has broad activity against enteroviruses but is not widely available and has no trial data for encephalitis or radiculoneuropathy 1.
Combination nucleoside analogues showed partial benefit in one case report of enterovirus-associated radiculoneuropathy in an HIV-infected patient 4.
Critical Care Considerations
Patients with severe enterovirus radiculoneuropathy require:
- Urgent ICU assessment if consciousness is declining for airway protection, ventilatory support, and management of raised intracranial pressure 1
- Access to neuroimaging (MRI and CT) and neurophysiology (EEG) 1
- Transfer to a specialist neuroscience unit within 24 hours if diagnosis is unclear or patient fails to improve 1
Common Pitfalls
- Do not delay supportive care while awaiting IVIG - the primary management is intensive supportive care 1
- Do not rely on serology for acute diagnosis - use CSF PCR instead 1
- Screen for IgA deficiency before IVIG administration to prevent anaphylaxis 1, 5
- Recognize that immunosuppressed patients, even with mild hypogammaglobulinemia, are at high risk and warrant more aggressive consideration of IVIG 2