Reversible Cerebral Vasoconstriction Syndrome and Fingolimod: Culprit or Innocent Bystander (P2.224)

OBJECTIVE: To describe a case of reversible cerebral vasoconstriction syndrome (RCVS) in a patient after starting oral Fingolimod for multiple sclerosis. BACKGROUND: Fingolimod is an oral medication for treatment of multiple sclerosis that works through the sphingosine 1-phosphate (S1P) receptor system. S1P receptors, specifically the S1P(3) subtype, are present on endothelial vessel cells and have been shown to induce vasoconstriction of cerebral arteries in animal studies. RCVS manifests with severe headaches and segmental constriction of cerebral arteries on angiogram. RCVS has been associated with medications, including serotonergic and adrenergic drugs, but to date there have been no reports of RCVS in patients taking Fingolimod. DESIGN/METHODS: Case Report RESULTS: We present a 47 year old woman with multiple sclerosis with acute onset, severe diffuse headache with recurrent thunderclap-like worsening of her pain that developed four weeks after starting Fingolimod. Her examination was non-focal and initial CT brain and MRI brain were without blood, stroke, or mass lesion. Cerebral angiogram showed diffuse areas of focal narrowing and dilatation. An extensive work-up for inflammatory and infectious etiologies was negative, including two normal cerebrospinal fluid examinations (with the exception of oligoclonal bands), normal serum inflammatory markers and complement levels, and negative ANA, ANCA, and rheumatoid factor. Fingolimod was discontinued and after failing prior treatment with intravenous steroids and oral verapamil, the patient was treated with oral nimodipine for presumed vasospasm, with significant improvement in her headache. A repeat cerebral angiogram one month later demonstrated marked improvement in vasospasm. There was no recurrence of symptoms after tapering off nimodipine and Fingolimod was not restarted. CONCLUSIONS: Reversible cerebral vasoconstriction syndrome may be a rare complication of Fingolimod treatment and should be considered in patients with new onset thunderclap headache. The mechanism likely involves the effects of Fingolimod on S1P(3) receptors on cerebral arteries. Disclosure: Dr. Fleming has nothing to disclose. Dr. West has nothing to disclose.