N. Asgari
Institute of Regional Health Research

Author Of 1 Presentation

 Program
Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

PS15.03 - Optical coherence tomography in aquaporin-4-IgG positive neuromyelitis optica spectrum disorders: a collaborative multi-center study

Speakers
Authors
Presentation Number
PS15.03
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease
Lecture Time
13:15 - 13:27

Abstract

Background

Optic neuritis (ON) is a frequent manifestation in aquaporin-4 antibody (AQP4-IgG) seropositive neuromyelitis optica spectrum disorders (NMOSD). Due to limited samples, existing optical coherence tomography (OCT) studies are inconsistent regarding retinal changes in eyes with a history of ON (NMO-ON) and without a history of ON (NMO-NON), and their functional relevance.

Objectives

The CROCTINO (Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica) project aims to reveal correlates of retinal pathology and to generate hypotheses for prospective OCT studies in NMOSD. The objective of this study was to analyze retinal changes of AQP4-IgG seropositive NMO-ON and NMO-NON eyes in an international cross-sectional OCT dataset.

Methods

Of 656 subjects, we enrolled 283 AQP4-IgG seropositive NMOSD patients and 72 healthy controls (HC) from 22 international expert centers. OCT data was acquired with Spectralis SD-OCT, Cirrus HD-OCT and Topcon 3D OCT-1. Mean thickness for the combined ganglion cell and inner plexiform layer (GCIP) and inner nuclear layer (INL) were calculated from macular volume scans. Clinical, functional and laboratory testing were performed at discretion of each center.

Results

We compared NMO-ON eyes (N = 260), NMO-NON eyes (N = 241) and HC eyes (N = 136). GCIP was reduced in NMO-ON (57.4 ± 12.2 µm) compared with NMO-NON (75.9 ± 7.7 µm; p < 0.001) and HC (81.4 ± 5.7 µm; p < 0.001). NMO-NON had thinner GCIP (p < 0.001) compared with HC. INL was thicker in NMO-ON (40.3 ± 3.9 µm) compared with NMO-NON (38.6 ± 3.9µm; p < 0.001), but not HC (39.4 ± 2.6 µm). Microcystic macular edema were visible in 6.6 % of NMOSD eyes.

Conclusions

AQP4-IgG seropositive NMOSD is characterized by a functionally relevant loss of retinal neuroaxonal content and a - probably inflammatory - increase of INL after ON. Our study further supports the existence of attack-independent damage in the visual system of patients with AQP4-IgG seropositive NMOSD.

Collapse

Author Of 3 Presentations

 On-Demand Program
Imaging Late Breaking Abstracts

LB1177 - PAMRINO: International MRI and clinical data repository for neuromyelitis optica spectrum disorder (ID 469)

Speakers
Authors
Presentation Number
LB1177
Presentation Topic
Imaging

Abstract

Background

Neuromyelitis optica spectrum disorders (NMOSD) encompasses a group of rare inflammatory diseases which primarily target the optic nerves, spinal cord, and brain. Typically, magnetic resonance imaging (MRI) data from single-center studies comprise 20-50 patients, limiting statistical power for outcomes research. Using retrospective data from the PArallel MRI in NmOsd (PAMRINO) study, a novel prospective NMOSD image repository (NMOsDIR) representing multiple international sites was coordinated by Charité-Universitätsmedizin Berlin and the Medical Image Analysis Center (Basel).

Objectives

The PAMRINO study aimed to investigate and analyze retrospective MRIs collected from NMOSD-specialized centers, potentially for the evaluation of disease-related brain and spinal cord changes. NMOsDIR serves as an international imaging research resource (comprising standardized retinal optical coherence tomography and MRI scans) and clinical data hub for prospective studies in NMOSD. Linking imaging and clinical data, as well as enabling analysis pipelines for each modality, will facilitate multi-centered studies using sufficient data and statistical power to advance outcomes research in this rare disease.

Methods

For clinical data collection in PAMRINO, a Research Electronic Data Capture (REDCap) platform was used, where participating centers entered data relevant for NMOSD patient monitoring. An image database (XNAT) was established for image uploads. This large collection of MRI data is currently being analyzed in a joint international effort of NMOSD clinical neuroradiologists and scientists.

Results

Brain, spinal cord, and optic nerve MRI scans with associated clinical data were collected from 514 NMOSD patients and 56 healthy controls from 17 international centers. Roughly 20,000 individual MRI scans from patients and healthy controls were collected. Of these, 78% had T1-weighted cerebral MRIs (55% with 3D scans), 80% had T2-weighted cerebral MRIs (54% with 3D scans), 86% had T2-weighted spinal cord MRIs (55% with 3D scans), and 35% had optic nerve MRIs.

Conclusions

We successfully established PAMRINO, an international collaborative retrospective MRI and clinical data repository. The knowledge gained during this process provided important new insights, where the initial analysis of the dataset has underscored the large degree of heterogeneity in image and clinical data collection in NMOSD-specialized centers. Thus, calling for more standardized methods of data acquisition and imaging analysis, as not to limit research opportunities. The new longitudinal, prospective NMOsDIR will help us to answer many pressing - yet open - questions regarding patients seropositive for aquaporin-4-IgG+, myelin oligodendrocyte glycoprotein-IgG+ and other autoimmune-related diseases. In turn, such a strategy will strengthen future capabilities in research, diagnosis, monitoring and improving NMOSD patient care.

Collapse
Biomarkers and Bioinformatics Poster Presentation

P0086 - Highly sensitive quantitation of CXCL13 as an intrathecal biomarker in optic neuritis (ID 718)

Speakers
Authors
Presentation Number
P0086
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

CXCL13 chemokine is a key regulator of B cell chemotaxis and CXCL13 in cerebrospinal fluid (CSF) is of pathophysiological relevance in multiple sclerosis (MS).

Objectives

To assess the potential value of a highly sensitive CXCL13 assay in acute optic neuritis (ON) patients for prediction of MS.

Methods

A Simoa CXCL13 assay was used to measure CXCL13 in CSF and serum of two independent, treatment-naïve ON cohorts: A training cohort (TC) derived from a population-based cohort (n = 33) and a validation cohort (VC) of patients collected consecutively in line with the population study precepts (n = 30). Prospectively, 14/33 patients from the TC and 12/30 patients from the VC showed progression to MS (MS-ON). The remaining 19/33 from TC and 18/30 from VC were considered as isolated ON (ION). A group of healthy controls (HC, n = 11) were used for comparison.

Results

CXCL13 was detectable in all samples. General ON patients had higher CXCL13 than HCs (p = 0.012). In the TC, CXCL13 in MS-ON patient CSF was higher than in ION and HC (p = 0.0001 and p<0.0001, respectively). This was confirmed in the TC, where MS-ON patients too showed increased CSF CXCL13 relative to ION (p = 0.0091). Logistic regression analysis showed area under curve of 0.83 (95% confidence interval: 0.73-0.93) and an odds-ratio of 19.6 at the optimal cutoff.

Conclusions

Increased ability to detect CSF CXCL13 using the Simoa assay allowed identification of ON patients and segregated MS-ON from ION. These data indicate a promising potential of this assay, and further studies are warranted.

Collapse
Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0717 - Frequency of comorbidities in Neuromyelitis Optica spectrum disorder (ID 459)

Speakers
Authors
Presentation Number
P0717
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Comorbidity may influence clinical aspects of neuromyelitis optica spectrum disorder (NMOSD). However, there is little knowledge regarding the interaction between comorbidities and NMOSD.

Objectives

We conducted this study to estimate the prevalence of comorbidities in NMOSD patients and assessed their association with disease outcomes.

Methods

This retrospective study assessed records of patients ( interview and medical report abstraction) from 2008 to 2019, categorizing comorbidities into three groups: somatic, psychiatric and autoimmune. We also evaluated the smoking status and BMI as health factors. Severity of disease was evaluated by the Expanded Disability Status Scale (EDSS), progression index (PI) and annualized relapse rate. The frequency of comorbidities was compared between anti-aquaporin 4 antibody (AQP4-IgG) seropositive and matched seronegative patients. Unadjusted and adjusted regression analysis were performed to assess the association between disease outcomes with comorbidities. To compare the frequency of comorbidities between AQP4-IgG seropostive and seronegative patients, we performed propensity score matching (PSM)

Results

A total of 115 NMOSD patients were enrolled. Fifty-five (47.8%) patients reported at least one comorbidity. In total, 69 comorbidities were found, of which 44 occurred prior to NMOSD onset: 43 somatic, 22 psychiatric and four autoimmune entities. The most common comorbidities were migraine 11/115 (9.6%), anxiety disorders 11/115 (9.6%), major depression disorder n=9 (7.8%), iron deficiency anemia 9/115 (7.8%) and non-autoimmune hypothyroidism 8/115 (7.0%). Two patients reported cancer (breast cancer and pituitary adenoma ) Autoimmune conditions were present in four cases: three patients with SLE (2.6%) and one patient with Sjogren’s syndrome (SS). Thirty-six (31.3%) patients were underweight and 19 (16.5%) were overweight with no obese patients (the mean BMI in the whole group: 20.42±3.64). There were 14 (12.1%) ever smokers in the study cohort with the mean of number of packs-years of 11.58±14.95. Psychiatric comorbidities associated with PI in unadjusted (OR=0.649, 95% CI=0.120, 1.178, P=0.017) and adjusted models (OR=0.506, 95% CI=0.082, 0.930, P=0.020). After stratification for AQP4-IgG no significant difference in frequency of comorbidities and outcomes were observed.

Conclusions

Our results showed that half the patients had comorbidities, suggesting screening for comorbidity as part of NMOSD care.

Collapse