Neurology AdvisorEBV Antibody Titers May Distinguish MS From Other Neurologic Diseases

Persistently elevated Epstein‑Barr virus nuclear antigen 1 (EBNA‑1) IgG antibody titers distinguished multiple sclerosis from MOGAD and NMOSD over time in a large multicenter study published in JAMA Neurology, supporting longitudinal serologic monitoring as a potential diagnostic adjunct.

Editorial Note
Results support a diagnostic adjunct, not a replacement for established criteria. EBV antibody trends should be integrated with clinical and imaging data.

Clinical Considerations

• Sustained high EBNA‑1 IgG titers were observed in over 95% of patients with MS but in fewer than 20% with MOGAD or NMOSD.
• Longitudinal measurements, rather than single time points, provided clearer differentiation between conditions.
• Persistent titers distinguished MS from aquaporin‑4–seronegative NMOSD, a common diagnostic challenge.
• Diagnostic accuracy exceeded 90% when high titers appeared in two or more samples.

Practice Applications

• Consider longitudinal EBNA‑1 antibody testing as an adjunct in diagnostically ambiguous cases.
• Avoid reliance on single EBV antibody measurements, which showed limited discriminatory value.
• Space repeat testing approximately 4–5 months apart to identify persistent immune responses.
• Integrate findings alongside imaging, clinical presentation, and existing biomarkers.

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