Ocrelizumab is a novel antiCD20 antibody approved by FDA for Relapsing Remitting Multiple sclerosis (RRMS) in 2017. Adverse events reported during Phase 3 trials (OPERA I and II) included infusion related reactions, respiratory tract infection, hepatitis B re-activation, and oral/genital herpes infection. Post marketing surveillance have shown varicella infections and herpetic encephalitis. To our knowledge we report the first known case of Varicella Zoster Virus (VZV) encephalitis after initiation of ocrelizumab therapy in a 46-year old man with MS.

A 46-year-old male presented with one week of generalized malaise, fever, agitation, and confusion. He had history of RRMS previously treated with dimethyl fumarate and teriflunomide later transitioned to ocrelizumab 4 months prior to current presentation. Expanded Disability Status Scale (EDSS) was 3. Exam was unremarkable other than presence of inattention and generalized hyperreflexia. Investigations revealed peripheral neutrophilic leukocytosis (WBC 17000/mm³, 86.9% neutrophils) unremarkable blood chemistries and urinalysis, blood and urine cultures. He was empirically treated for meningitis in an immunocompromised host with vancomycin, ceftriaxone, and acyclovir. Head imaging was unremarkable for any acute changes. CSF showed WBC 133/mm³ with 90% lymphocytes, RBC 174/mm³, protein 115 mg/dL. VZV DNA was detected on PCR with viral load of 35,100 IU/L. Serum IgG level was normal (833 mg/dL). Patient was treated with intravenous acyclovir for 3 weeks with resolution of symptoms.