Reversible cerebral vasoconstriction syndrome in association with fingolimod use

Abstract

Background: Reversible cerebral vasoconstriction syndrome (RCVS), also known as Call-Fleming syndrome, is characterized by thunderclap headaches, non-aneurysmal segmental cerebral vasoconstriction seen on arteriogram, and spontaneously resolves within 12 weeks. Fingolimod has been reported to cause posterior reversible encephalopathy syndrome (PRES) and one case of RCVS. Objective: We report a case of RCVS possibly related to fingolimod use, and compare to cases of adverse outcomes in fingolimod use. Methods: This is a single observational study without controls; therefore, level of evidence is IV. A literature review in pubmed with keywords, fingolimod, vasospasm, RCVS, Call-Fleming, stroke, PRES and hemorrhage. Results: One case of RCVS on fingolimod in the post-partum period. Two other cases in the literature were found one with hemorrhagic encephalitis and the other critical vasospasm in the upper extremity associated with fingolimod 1.25 mg daily in the FREEDOMS II trial and TRANSFORMS study, respectively. Additionally, Novartis reports nine cases of PRES related to fingolimod use. Conclusion: Fingolimod has the potential to cause vasoconstriction however appears to be rare and more likely on doses higher than 0.5 mg daily. Fingolimod may be associated in RCVS and should be considered in patients with severe headache on fingolimod.

Keywords:

• Multiple sclerosis, fingolimod, reversible cerebral vasoconstriction syndrome, Gilenya
• cerebral hemorrhage

Acknowledgements

Dr Belliston was a National MS Society Clinical Fellow and received a Postdoctoral MS Clinical Fellowship Grant from Biogen Idec during the time he worked on this case study.

Declaration of Interest

Dr Belliston has no reported disclosures. Dr Sundarajan has no reported disclosures. Dr Newell has no reported disclosures.

Dr Hammond has received research funding from Sunovion and speakers honorarium from Cyberonics. Dr Lynch has received grant/research support from Actelion, Bayer, BiogenIdec, Cephalon, Cognition, Eli Lily, EMD Serono, Genzyme, Novartis, OnoPharma, Pfizer, Receptos, and Teva Neuroscience.