Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders

Abstract

ObjectiveTo investigate if patients with neuromyelitis optica spectrum disorder (NMOSD) develop subclinical visual pathway impairment independent of acute attacks.MethodsA total of 548 longitudinally assessed full-field visual evoked potentials (VEP) of 167 patients with NMOSD from 16 centers were retrospectively evaluated for changes of P100 latencies and P100-N140 amplitudes. Rates of change in latencies (RCL) and amplitudes (RCA) over time were analyzed for each individual eye using linear regression and compared using generalized estimating equation models.ResultsThe rates of change in the absence of optic neuritis (ON) for minimal VEP intervals of ≥3 months between baseline and last follow-up were +1.951 ms/y (n = 101 eyes; SD = 6.274; p = 0.012) for the P100 latencies and −2.149 µV/y (n = 64 eyes; SD = 5.013; p = 0.005) for the P100-N140 amplitudes. For minimal VEP intervals of ≥12 months, the RCL was +1.768 ms/y (n = 59 eyes; SD = 4.558; p = 0.024) and the RCA was −0.527 µV/y (n = 44 eyes; SD = 2.123; p = 0.111). The history of a previous ON >6 months before baseline VEP had no influence on RCL and RCA. ONs during the observational period led to mean RCL and RCA of +11.689 ms/y (n = 16 eyes; SD = 17.593; p = 0.003) and −1.238 µV/y (n = 11 eyes; SD = 3.708; p = 0.308), respectively.ConclusionThis first longitudinal VEP study of patients with NMOSD provides evidence of progressive VEP latency delay occurring independently of acute ON. Prospective longitudinal studies are needed to corroborate these findings and help to interpret the clinical relevance.

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

“…As shown in other studies, no significant differences in latency or amplitude of the P100 component were found based on AQP4 serostatus (Watanabe et al, 2009;Ringelstein et al, 2014Ringelstein et al, , 2020. However, we noted a significantly higher prevalence of the absence of response in at least one eye in patients with NMOSD who were AQP4[+] (44%) vs. AQP4[-] (4%).…”

“…The logistic regression model revealed a significant association between AQP4-positive status and a higher rate of absentVEP responses, but no such relationship was found for the rate of abnormal responses. Notably, in a recent longitudinal study by Ringelstein et al, NMOSD patients with no history of ON showed a progressive delay in latency, which was not attributed to serostatus (Ringelstein et al, 2020). In view of this, we suggest that AQP4-positive status results in a worse outcome in VEP responses, which is mainly expressed in patients with severe impairment of the optic nerve.…”

“…Among studies exploring the relationship between AQP4 status and VEP measurements, a higher rate of 'unevoked' responses was found among individuals with AQP4-seropositive NMOSD, but none of these studies have found significant differences in the amplitude and latency of the P100 component with regard to AQP4 serostatus (Watanabe et al, 2009;Ringelstein et al, 2014;Ringelstein et al, 2020). The aims of this study were (i) to describe VEP responses in patients with NMOSD; (ii) to analyze the responses based on a scoring system; and (iii) to investigate the association between the responses and AQP4 antibody status.…”

Altered fovea in AQP4-IgG–seropositive neuromyelitis optica spectrum disorders

“…Occasionally, studies have reported neuroaxonal damage also in eyes without prior ON in AQP4-IgG-seropositive NMOSD, which could be interpreted as evidence as such. 39 However, earlier studies had cohort heterogeneity due to incomplete antibody characterization or inclusion of patients with antibody-negative NMOSD. Furthermore, ON in NMOSD often occurs near the chiasm, and neuroaxonal damage can be caused by chiasmal crossover from an affected eye to the fellow eye, 40 which might not be clinically apparent.…”

Disability Outcomes in the N-MOmentum Trial of Inebilizumab in Neuromyelitis Optica Spectrum Disorder

“…[1][2][3][4] Accrual of severe disability in NMOSD appears to be driven primarily by irreversible attack-related injury, although emerging evidence suggests that subclinical disease processes may be present. [5][6][7][8] Immunosuppression is typically used in NMOSD to reduce the risk of attacks. There are limited data on the effect of drugs used empirically in NMOSD on disability.…”