A 49-year-old female neuromyelitis optica spectrum disorder (NMOSD) patient with positive anti-aquaporin 4 (AQP4) antibody was treated with fingolimod (FTY720). Ten days later, she developed acute disturbance of consciousness, aphasia, right hemi-spatial neglect, and right hemiparesis. Brain MRI showed multiple white-matter lesions with slight Gadolinium enhancement. She was diagnosed of acute exacerbation of NMOSD. Thus, fingolimod may be associated with the development of a fulminant course in NMOSD patients with positive anti-AQP4 antibody.