A study recently published in the Journal of NeuroVirology found that viral infections often precede neuromyelitis optica spectrum disorders (NMOSD), and varicella zoster virus (VZV) could be the most common agent involved. The study describes a plausible causal relationship between VZV infection and NMOSD that may represent an unusual clinical scenario posing several diagnostic and management challenges.

Turco and colleagues collaborated on reviewing the available literature on PubMed and Embase to uncover the association between NMOSD and VZV infection from 1975 to 2020. The patients analyzed in the 13 articles were all female with VZV preceding NMOSD, and the median age of NMOSD presentation was 28.5 years.

Although the exact etiology and pathogenesis of NMOSD require further investigation, complex interactions between genetic and environmental factors are thought to play a part in its development. From the literature reviewed regarding NMOSD pathogenesis, the authors wrote: “(i) VZV seems to trigger only longitudinally extensive transverse myelitis (LETM), where no aquaporin-4 (AQP4) serologically ascertained optic neurites were detected); (ii) VZV seems to trigger LETM attacks and not the disease itself.”

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Additionally, VZV-related LETM was found to be preceded by a previous attack (area postrema syndrome) that was not triggered by VZV. This finding requires further studies to elucidate the exact role of antecedent and concomitant infection with neurotropic viruses in NMOSD course and the occurrence of clinical relapses. 

On the other hand, the authors point out that bystander activation may be a possible mechanism that can explain the association between autoimmunity and viral infections in NMOSD. This process occurs when microbes damage AQP4-rich tissue, provoking the activation of AQP4-specific T- and B-cells against the central nervous system (CNS) and molecular mimicry, which involves the production of antibodies that recognize both microbial epitopes and self-epitopes.

Recent data have suggested that infection could activate an inflammatory cascade with increased cerebrospinal fluid interleukin 6, which promotes anti-AQP4 antibody production from plasmablasts.

In brief, NMOSD is a severe, inflammatory, immune-mediated astrocytopathy of the CNS, characterized by recurrent inflammatory events primarily involving optic nerves and the spinal cord. Its spectrum has been expanded with the increasing availability of an anti-AQP4 antibody test, which is highly sensitive and specific for NMOSD.


Turco EC, Curti E, Pisani F, Granella F. Herpes zoster preceding neuromyelitis optica spectrum disorder: casual or causal relationship? A systematic literature review. J Neurovirol. Published online April 24, 2022. doi:10.1007/s13365-022-01065-4