Severe Neuroinvasive West Nile Virus in Association With Anti-CD20 Monotherapy for Multiple Sclerosis
Simon Thebault, Stephanie Gandelman, Camryn Lane, Erin Kim, Caitlin Pileggi, Leah Zuroff, Luana D. Yamashita, Matthew K. Schindler, Charles Y. Chiu, Michael R. Wilson, Joseph R. Berger, Clyde Markowitz, Amit Bar‐Or, R. A. Fuller, Rachel Brandstadter, Amy A. Pruitt, Dina Jacobs
Abstract
<h3>Objectives</h3> The objective of this study was to report on the development of neuroinvasive West Nile virus (WNV) infection in the context of anti-CD20 monotherapy for multiple sclerosis (MS). <h3>Methods</h3> This is a case series study. <h3>Results</h3> In 2021–2022, we observed 4 cases of neuroinvasive WNV infection in our patient population of 2009 patients with MS on ocrelizumab, compared with a total of 46 cases of neuroinvasive WNV infection reported in Pennsylvania and 40 in New Jersey. Odds were 258 times that of the general population (95% confidence interval 97–691), χ<sup>2</sup><i>p</i> < 0.0001). All were women aged 41–61 years with variable disease duration, level of disability, and duration of anti-CD20 therapy. All presented in summer/early fall with fever, headache, and encephalopathy consistent with meningoencephalitis. Three patients had acute cerebellitis. Two had anterior nerve root involvement progressing to quadriparesis, and 1 developed refractory nonconvulsive status epilepticus. All required intubation and experienced significant morbidity. All had CSF pleocytosis. Two patients were WNV IgM positive in both the serum and CSF, 1 patient had positive serum IgM and CSF metagenomic next-generation sequencing (mNGS), while 1 had positive CSF mNGS with negative serum and CSF antibodies. <h3>Discussion</h3> Neuroinvasive WNV infection can develop with anti-CD20 monotherapy in the absence of additional immunosuppression. WNV serologies may be negative in the setting of anti-CD20 treatment; in the appropriate clinical context, one should consider direct detection methods such as PCR or mNGS-based testing.