VZV encephalitis that developed in an immunized patient during fingolimod therapy

We report the case of a 66-year-old woman with progressive relapsing multiple sclerosis (MS) who developed varicella-zoster virus (VZV) encephalitis while on fingolimod despite vaccination. She presented with a stuttering course over several weeks. Five months after starting fingolimod, she was treated for a presumed MS flare with a 5-day course of high-dose IV methylprednisolone. A brain MRI showed stable chronic white matter lesions. She presented 18 days later with transient word-finding difficulty, was diagnosed with a TIA, and started on aspirin and a statin. She presented 9 days later after a generalized tonic-clonic seizure; she had no history of prior seizures. Levetiracetam was started, and dalfampridine was stopped, with control of her seizures. During this admission, MRI showed restricted diffusion and T2 hyperintensity in the left caudate head. CSF had glucose of 50, protein of 74, 13 erythrocytes, 133 leukocytes (61% lymphocytes); VZV was detected by PCR (other viral studies were negative; CSF VZV immunoglobulin M and immunoglobulin G [IgG] were not assessed). In the interval preceding this admission, uveitis was diagnosed in her right eye; while there were no skin vesicular lesions, in retrospect we consider the uveitis a likely manifestation of VZV infection. Fingolimod was stopped, and she was treated for 11 days with IV acyclovir, but her mental status worsened 5 days after stopping acyclovir. A subsequent MRI showed progression of the caudate lesion (figure, A and B) thought to be caused by direct parenchymal infection, so she was restarted on IV acyclovir and steroids with clinical improvement and eventual discharge to a rehabilitation facility.