This is a case of a young female who presented with an initially nonfocal and vague examination with fulminant worsening whilst inpatient including tetraplegia, neurogenic bladder and progressive mental status changes. Serum AQP4 IgG titer was high confirming NMOSD diagnosis. After acute respiratory decompensation necessitating intubation, a CT chest revealed lymphadenopathy with concern for breast tumor. Her neurological function continued to deteriorate with follow up MRI revealing extensive CNS demyelination not visualized ~1 week prior. Repeat CT showed worsening lymphadenopathy, tissue biopsy confirmed triple-negative stage IV breast cancer. The resected tumor was sent for immunostaining and the neoplastic cells stained positive for AQP4 expression. 

This case along with the available literature suggests the need to consider paraneoplastic causes in especially aggressive NMOSD. Increasing immunostaining capabilities combined with increasing clinician suspicion for paraneoplastic causes will lead to a better understanding of the true incidence of paraneoplastic NMOSD as well as improved diagnosis and treatment of these patients.