The relationship between aquaporin-4 antibody status and visual tract integrity in neuromyelitis optica spectrum disorders: A visual evoked potential study

Abstract

BackgroundOptic neuritis (ON) is one of the hallmark symptomatic features of neuromyelitis optica spectrum disorders (NMOSD). The majority of patients with NMOSD present highly specific autoantibodies against aquaporin-4 (AQP4). A number of studies have reported poor visual acuity outcomes in individuals with AQP4 seropositive NMOSD, but no such relationship has been found with regard to visual evoked potentials (VEP) parameters such as the amplitude and latency of the P100 component. In this paper, we aimed (i) to describe VEP responses in patients with NMOSD; (ii) to analyze those results based on a scoring system; and (iii) to investigate the association between the VEPs and AQP4 antibody status. MethodsWe retrospectively analysed the VEP responses of 40 patients with a diagnosis of NMOSD (according to the 2015 IPND criteria), including 16 with AQP4-postive status (AQP4[+]) and 24 with AQP4-negative status (AQP4[-]). In the first step, we measured the P100 peak latency and P100-N2 peak-to-peak amplitude in each patient. In the second, we converted these measures to the VEP score (0–10) using the scoring proposed by Jung et al. (2008). All recordings were performed using the same VEP device and testing protocol. ResultsAbnormal VEPs were recorded in 25 of 40 patients (62.6%). Of these, 17 (42.5%) had prolonged P100 latency, and 8 (20%) had no response detected in at least one eye. The patients with ON as the initial relapse symptom had significantly higher median VEP scores than those who experienced the longitudinally extensive transverse myelitis (LETM) at the disease onset (7.0 [in­terquar­tile range (IQR), 2.0–8.0] vs. 0.0 [IQR, 0.0–4.0], p<0.001). A lack of VEP response in at least one eye was detected more frequently in the AQP4[+] group than the AQP4[-] group (7/16 vs. 1/24, p<0.005). Logistic regression model controlling for age, gender, disease duration, and the type of relapse at onset showed an independent impact of AQP4[+] status (OR=35.45, p = 0.018) on the higher rate of absent VEP responses. In the entire group of patients (n = 40), those with AQP4[+] showed a small tendency towards a higher median VEP score (4.0 [IQR, 0.0–7.8] vs. 1.0 [IQR, 0.0–4.0], p = 0.304). Among individuals with abnormal responses (n = 25), the patients with AQP4[+] had significantly higher median VEP scores (7.0 [IQR, 4.0–8.5] vs. 3.0 [IQR, 1.0–7.0], p = 0.034) and more common bilateral involvement of the optic tracts (80% vs. 40%, p = 0.048) than those who were seronegative for anti-AQP4 antibody. A median regression analysis model controlling for age, gender, disease duration, type of onset, and number of relapses in last 12 months showed an independent association between the AQP4-positive status and a higher VEP score in patients with NMOSD (t = 2.882, df=2, p = 0.007). ConclusionVEP study remains a useful tool in the assessment of NMOSD patients. Due to the high prevalence of absent VEPs in NMOSD patients, the scoring system appears to be more applicable for the precise analysis of VEP recordings. There is a positive association between the AQP-positive serostatus and the poorer outcome in VEP responses, especially in patients with severe impairment of the optic nerve(s).