Objectives 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). Methods This is a case series study. Results 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), χ²p < 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. Discussion 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.

Anti-CD20 therapies have proven to be highly effective and safe therapies for multiple sclerosis (MS) and have had rapid uptake in the MS community. However, no clear consensus has arisen regarding an approach to screening or surveillance lab monitoring. Based on current evidence, for screening labs before anti-CD20 initiation, we propose checking liver function test (LFT), complete blood count with differential (CBC), absolute B-cell count, quantitative immunoglobulins, hepatitis B virus serologies, varicella zoster virus IgG, John Cunningham virus (JCV) status, and age-appropriate vaccination history. For surveillance monitoring in an otherwise asymptomatic individual, we propose biannual LFTs and CBC, quantitative immunoglobulins annually after year 3, absolute B-cell count at month 6 and in the setting of relapse, and JCV only if clinical or radiographic features of progressive multifocal leukoencephalopathy arise. For ublituximab, pregnancy testing is additionally recommended before each infusion. We propose evidence-based screening and safety surveillance labs which take into account likelihood of changing management in an otherwise stable or asymptomatic individual.

Background: New-onset Neuromyelitis Optica Spectrum Disorder (NMOSD) has rarely been reported in adults over age 70. We describe a severe presentation in a 77-year-old female. Case: The patient presented with left arm numbness, followed by left leg numbness and bilateral optic neuritis. Neuroimaging showed a C2-T1 lesion with C4-C7 holocord enhancement, and bilateral optic nerve enhancement extending to the optic chiasm. Serum testing detected anti-aquaporin-4 antibodies. She was left with dyschromatopsia, myelopathy, and ambulatory dysfunction. She had a history notable for rheumatoid arthritis, treated with rituximab, which had been discontinued six years prior to presentation. Discussion: Very-late-onset NMOSD encompasses a unique cohort of patients with significant immunogenicity despite immunosenescence. Limited data suggest diagnostic delays, severe morbidity, and decreased utilization of disease-modifying therapies.