Abstract
BACKGROUND: Aquaporin-4 IgG seropositive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD) might occur in association with cancer. According to diagnostic criteria, a probable paraneoplastic NMOSD can be diagnosed only in patients with isolated myelitis and adenocarcinoma or tumors expressing AQP4. The aim of this study was to explore the features of paraneoplastic NMOSD through a data-driven approach. METHODS: A systematic literature review was performed. Patients with AQP4-IgG positivity in association with tumor in the absence of history of checkpoint inhibitors administration/central nervous system metastases were included. Demographic, clinical, and oncological data were collected. A hierarchical cluster analysis (HCA) was performed and data were compared between resulting clusters. RESULTS: A total of 1333 records were screened; 46 studies (72 patients) fulfilled inclusion criteria. Median age was 54 (14-87) years; adenocarcinoma occurred in 41.7% of patients, and 44% of cases had multifocal index events. Cancer and NMOSD usually co-occurred. HCA classified patients in three clusters that differed in terms of isolated/multifocal attacks, optic neuritis, pediatric onset, and type of underlying tumor. Age, time from neoplasm to NMOSD onset, and tumor AQP4 staining did not differ between clusters. CONCLUSIONS: Our data-driven approach reveals that paraneoplastic NMOSD does not present a homogeneous phenotype nor peculiar features. Accordingly, cancer screening may be useful in AQP4-IgG NMOSD regardless of age and clinical presentation.