Varicella-zoster virus Neurovasculitis (VZV-NV) in the Setting of Autoantibodies to Interferon alpha (anti-IFNα)

BACKGROUND: VZV-NV resulting in CNS damage is rare in immunocompetent hosts. Humoral immunity protects against acquiring VZV, and T-cell mediated immunity shields against reactivation of the latent virus. Individuals who are immunocompromised due to T-cell mediated defects can present with systemic VZV. METHODS: Case report of a previously healthy man who developed VZV-NV associated with autoantibodies to IFNα. RESULTS: A previously healthy 64 year-old man developed an acute T3 Brown-Sequard syndrome. Symptoms progressed to include bilateral lower extremity weakness, ptosis, ophthalmoplegia, and encephalopathy. Magnetic resonance imaging (MRI) showed diffuse T2 hyperintensities with enhancement throughout the spine and brain, including enhancement of his meninges, roots, and cranial nerves. Successive cerebrospinal fluid (CSF) studies revealed increasing B-cell lymphocytosis, (maximum 661 cells/mcl), and CSF protein (maximum 242 mg/dL). CSF PCR was positive for VZV and IgM antibodies. Further testing showed anti-IFNα autoantibodies in the plasma and CSF. Serum anti-IFNα fluorescence intensity was 30 times normal, and his plasma blocked IFNα-induced STAT-1 phosphorylation in normal monocytes. Treatment with acyclovir and methylprednisolone resulted in improvement. Repeat LP following treatment revealed 32 WBC/mcl with normal protein. Follow-up MRI did not show any new lesions. Three years after initial presentation, he continues to be stable without clinical relapses, or subclinical changes on MRI. Serum studies were positive for VZV IgG and negative for IgM. CSF PCR was positive for VZV. Lastly, serum anti-IFNα fluorescence intensity remained 25 times normal, and his plasma continued to block IFNα-induced STAT-1 phosphorylation in normal monocytes. CONCLUSION: This is the first identified case of CNS VZV-NV in the setting of binding and blocking autoantibodies to IFNα in the serum and CSF. Elevated serum and CSF levels of anti-INFα may impair natural killer, T-cell and neuronal antiviral activity. Disruption of T-cell mediated immunity due to anti-IFNα could cause an adult-onset immunocompromised state with severe VZV reactivation. The association of high-titer neutralizing autoantibodies to INFα in an adult with CNS VZV is novel and may be clinically relevant. DISCLOSURES: All authors: No reported disclosures.