Actual issues of serum aquaporin-4 autoantibodies evaluation in the diagnostics of neuromyelitis optica spectrum disorders

Abstract

To analyze the usage and timeliness of aquaporin-4 antibodies (AQP4-IgG) serology test in the diagnostics of neuromyelitis optica spectrum disorders (NMOSD) in routine clinical practice. 27 patients with NMOSD were included in the study. All patients had a positive serum test for AQP4-IgG. A retrospective study of neurological manisfestations of attacks, timing and results of serology for AQP4-IgG was performed. The results were analyzed taking into account two types of attacks identified: a) HS (with highly specific manifestations for NMOSD), which are considered as indications for conducting the AQP4-IgG test and b) NS (with non-specific manifestations for NMOSD). A comparison of the time from HS attack to the AQP4-IgG test administration (T1, years), from HS attack to NMOSD diagnosis (T2, years) was undertaken as well as the number of attacks during these periods (N1, N2) were counted in three groups of patients. Group 1 - with the first HS attack before or in 2008 (n=6), group 2 - from 2009 to 2013 (n=12), group 3 - from 2014 to 2018 (n=9) accordingly. A statistically significant decrease in T1, T2, N1, N2 was found in successive time intervals of 5 years (p<0.05). In 8 of 27 (28.6%) patients the first attack of NMOSD was presented with non-specific symptoms (NS attack). In 7 patients (77.8%) of 9 misdiagnosed as multiple sclerosis (MS) an increase in attack frequency was found while on disease modifying therapies (DMTs) and increase in attack severity was found in 8 (88.9%). In all 9 cases the diagnosis was revised to NMOSD after AQP4-IgG test was performed with positive result. The time interval from disease course worsening while on DMTs until the test was 7 [4; 37] months, and the number of relapses - 2 [0; 3]. In 4 of 27 patients with suspected NMOSD, the repeated AQP4-IgG test only was positive for increased antibodies titer. The time interval between first test negative and retest administered was 20 [6.1; 47.8] months. In 3 of 4 patients (75%) one or more attacks occurred during this time period. In 4 patients the presence of AQP4-IgG in the first analysis was not followed by the diagnosis of NMOSD. In recent years, apropos AQP4-IgG test administration improved, but the problem remains with the timeliness for retest with first result negative. It is advisable to expand the indications for its use. The timeliness for serum AQP4-IgG retest in cases of unexplained deterioration in the course of proposed MS on DMTs and the lack of awareness of the test diagnostic value are still relevant.