Fingolimod is a disease-modifying treatment utilized in the treatment of relapsing-remitting multiple sclerosis. Fingolimod has been associated with an increased risk in herpes simplex and varicella infection in clinical trials. We report a case of cerebral venous thrombosis secondary to cryptococcus in a patient receiving fingolimod.

A 61-year-old male with multiple sclerosis treated with fingolimod presented with a two-week history of headache, chills, and night sweats. He was treated empirically for sinusitis with azithromycin. Subsequently he developed acute onset of slurred speech and dizziness. An MRI of the brain revealed a left transverse and sigmoid sinus thrombosis. Two blood cultures revealed Cryptococcus neoformans; a serum cryptococcal antigen was also positive. HIV testing was negative. A lumbar puncture was deferred as the patient was placed on heparin and subsequently warfarin for the cerebral venous thrombosis. The patient received antifungal therapy for 14 days with liposomal amphotericin B and flucytosine, followed by oral fluconazole for 8 weeks. He was subsequently re-admitted 60 days later with bilateral papilledema; his anticoagulation was reversed, and a lumbar puncture revealed a negative cryptococcal antigen and an intracranial pressure of 20. A repeat MRI revealed worsening superior sagittal sinus thrombosis, thought to be the cause of the papilledema; his anti-coagulation was re-initiated. He received a brief course of intravenous methylprednisolone but as his multiple sclerosis was well-controlled, further therapy was deferred. His symptoms had resolved at a 3-month follow-up appointment.

This is the first report of a multiple sclerosis patient treated with fingolimod to develop cerebral venous thrombosis secondary to cryptococcal fungemia. Fingolimod has been associated with cryptococcal meningoencephalitis, cutaneous cryptococcosis, and disseminated cryptococcosis. Cryptococcus is a rare cause of cerebral venous thrombosis in HIV-negative hosts. The risks of opportunistic infections should be considered in patients managed with fingolimod.