Cerebral Venous Thrombosis due to Cryptococcus in a Multiple Sclerosis Patient on Fingolimod

Abstract

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 2-week history of headache, chills, and night sweats. 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 readmitted 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 anticoagulation was reinitiated. 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. The risks of opportunistic infections should be considered in patients managed with fingolimod.

Keywords: Cerebral venous thrombosis; Cryptococcus; Fingolimod; Multiple sclerosis.

Fig. 1

MRI T1-weighted images, axial sections − first admission, hospital day 1.