Clinical spectrum of CNS aquaporin-4 autoimmunity

Objectives: Traditionally, neuromyelitis optica (NMO) was known to involve only the optic nerves and spinal cord. However, the discovery of highly specific anti-aquaporin-4 (AQP4) antibody for NMO enabled us to identify more diverse clinical manifestations. Here, we describe the demographic and clinical characteristics of patients who were anti-AQP4-antibody positive, represented by CNS AQP4 autoimmunity. Methods: In total, 388 consecutive patients with inflammatory demyelinating CNS diseases were tested for the anti-AQP4 antibody and 106 seropositive patients who were positive by ELISA or cell-based assay were included. Results: Ninety-seven patients were women, and 9 men. The median age at onset was 32 years. The median annualized relapse rate was 1.14 during the median follow-up of 7.0 years. When the 2006 revised diagnostic criteria for NMO were applied, 72% of patients met the criteria, and 28% had a limited form of NMO. Brain symptoms were observed in 51% of patients, and 24% of patients presented with brain symptoms as their first manifestation. Severe residual visual impairment or ambulatory disability was observed in 42% of patients. The median intervals to Expanded Disability Status Scale (EDSS) 6 and severe visual impairment in at least one eye were 12 and 11 years, respectively. A multivariate analysis revealed a delay of more than 4 years before appropriate immunotherapy was independently associated with reaching severe disability of more than EDSS 6. Conclusion: The spectrum of neurologic manifestations and the disease course associated with CNS AQP4 autoimmunity is broader than previously recognized.