Faculty Bibliography

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system autoimmune inflammatory condition associated with aquaporin-4-immunglobulin antibodies which results in demyelination. Understanding clinical and therapeutic predictors of relapses can aid management and prognostication of this disease Aim: To evaluate the effect of clinical and therapeutic predictors on risk of relapse and change in disability in NMOSD Methods: This MSBase cohort study of NMOSD patients (n=399) examined predictors of relapse in a Anderson-Gill survival model and change in expanded disability status score (EDSS) in a mixed effects model. A secondary analysis was conducted in the NMOantibody positive subgroup (>=1 core region affected: spinal cord, optic nerve or brainstem, n=202).
Result(s): Age (HR=0.82 per decade, p=0.003), disease duration (HR=0.95 per year, p=0.02), spinal cord onset (HR=0.6, p=0.007), brainstem onset (p=0.53, p=0.009) and treatment with azathioprine (HR=0.51, p< 0.001), mycophenolate mofetil (HR=0.24, p=0.016) were associated with a reduced risk of relapse in NMOSD. Treatment with glatiramer acetate (HR=1.82, p=0.028), interferon-beta (HR=1.57, p=0.013) and acute therapies-corticosteroids (HR=1.87, p < 0.001), intravenous immunoglobulin (HR=3.49, p=0.001) were associated with an increased risk of relapse. In the NMO-antibody positive subgroup, similar treatment effects on the risk of relapse were seen for azathioprine, mycophenolate mofetil, glatiramer acetate, corticosteroids and intravenous immunoglobulin. Age (p< 0.001), disease duration (p< 0.001), glatiramer acetate (p=0.001), and therapies used in acute relapses-cyclophosphamide (p=0.01), intravenous immunoglobulin (p=0.001) and plasma exchange (p< 0.001) were associated with a more pronounced increase in EDSS in the NMOSD cohort. Optic nerve onset (p=0.048), proportion of time pregnant (p=0.021) and treatment with azathioprine (p< 0.001), mycophenolate mofetil (p=0.043) and rituximab (p=0.029)-were associated with a slower increase in EDSS in the NMOSD cohort. The immunotherapies and age and disease duration showed similar associations in the NMO-antibody positive subgroup.
Conclusion(s): Treatment with azathioprine, rituximab and mycophenolate mofteil are associated with a slower increase in EDSS in NMOSD and a lower risk of relapses. The risk of relapses declines and accumulation of disability increases with age and disease duration in NMOSD

Background: Natural history studies in MS largely focused on determining time-to-disability benchmarks. Little is known about changes in MS symptom burden from patient's point of view. SymptoMScreen is an in-house developed and validated patientreported outcome (PRO) tool for assessing symptom severity in 12 domains commonly affected by

Introduction: Optical coherence tomography (OCT) is a valuable tool for quantifying retinal neuro-axonal damage in Neuromyelitis Optica Spectrum Disorders (NMOSD). However, existing OCT studies in NMOSD reveal inconsistencies due to non-standardised methods and limited sample sizes.
Objective(s): To collect and uniformly analyze a large international OCT dataset with corresponding clinical data for correlates of retinal damage in NMOSD in a multicenter approach (Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica, CROCTINO).
Aim(s): To facilitate optimization of international OCT standards, reveal potential correlates of NMOSD disease and retinal pathology, and generate hypotheses for prospective studies.
Method(s): Centers were mainly recruited from the GJCF-ICC network including experts in NMOSD clinical care and research. OCT images were collected as source data to allow for standardised quality control and analysis. Demographic and clinical metadata were obtained with electronic record forms, adhering to institutional review board approval. We included subjects with a) NMOSD per the 2015 International Panel criteria; b) longitudinal extensive transverse myelitis; c) recurrent optic neuritis; and d) healthy controls. Only subjects with available OCT source data and a complete information on age, sex, disease subtype and attack history were included.
Result(s): Data from 501 cases from 20 international centers were collected (148 Asia, 249 Europe, 36 North America, 68 South America). Age was 44+/-15 years (range, 10-85 years), with 84% female. A total of 470 patients fulfilled the 2015 NMOSD criteria, with 345 (73.4%) seropositive for aquaporin4 antibodies (AQP4- IgG) using a validated method. Of the AQP4-IgG-negative patients, 47 (37.6%; 9.4% of all patients) were MOG antibody seropositive, and 78 (62.4%, 15.6% of all patients) were double negative or had unknown antibody status. OCT was performed in 344 patients using Spectralis SD-OCT, in 102 using Cirrus HD-OCT and 55 using Topcon 3D OCT instruments. Healthy control data were available from 90 subjects from 4 centers (all Spectralis)
Conclusion(s): CROCTINO has collected the largest OCT dataset from NMOSD patients to date. Results from this international collaborative study should facilitate improved OCT practices in NMOSD, highlight clinical correlates of disease and retinal status, and prioritize hypothesis-testing to advance clinical care and research goals in the future