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1. Predictors of relapse in MOG antibody associated disease: a cohort study

Author

Saif Huda, Anu Jacob, Rachel Kneen, David Hunt, Mark Woodhall, Patrick Waters, Venkatraman Karthikeayan, Daniel Whittam, Patricia Kelly, Kerry Mutch, Richard Jackson, Katy Murray, and Sam Linaker

Subjects
Medicine
Abstract

Objective To identify factors predictive of relapse risk and disability in myelin oligodendrocyte glycoprotein associated disease (MOGAD).Setting Patients were seen by the neuromyelitis optica spectrum disorders (NMOSD) service in Liverpool, UK, a national referral centre for adult patients with MOGAD, NMOSD and related conditions.Participants Patients with MOGAD=76 from England, Northern Ireland and Scotland were included in this cohort study.Results Relapsing disease was observed in 55% (42/76) of cases. Steroid treatment >1 month (OR 0.2, 95% CI 0.05 to 0.80; p=0.022), transverse myelitis (TM) at first attack (OR 0.03, 95% CI 0.004 to 0.23; p=0.001) and male sex (OR 0.16, 95% CI 0.04 to 0.68; p=0.014) were associated with monophasic disease (area under the curve=0.85). Male sex (HR 0.46, 95% CI 0.24 to 0.89; p=0.011) and TM at disease onset (HR 0.42, 95% CI 0.22 to 0.82; p=0.011) were also associated with an increased latency to first relapse. 45% (32/71) of patients became MOG-antibody negative and in relapsing patients negative seroconversion was associated with a lower relapse risk (relative risk 0.11 95% CI 0.05 to 0.26; p

Published
2021
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2. Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO)

Author

Saif Huda, Anu Jacob, Joachim Havla, Adriana Roca-Fernández, Philipp Albrecht, Maria Isabel Leite, Friedemann Paul, Alexander U Brandt, Jae-Won Hyun, Frederike Cosima Oertel, Claudia Chien, Nasrin Asgari, Elena H Martinez-Lapiscina, Orhan Aktas, Svenja Specovius, Hanna G Zimmermann, Charlotte Bereuter, Marco Aurélio Lana Peixoto, Mariana Andrade Fontenelle, Alejandro Rubio Diaz, Fereshte Ashtari, Rahele Kafieh, Alireza Dehghani, Mohsen Pourazizi, Lekha Pandit, Anitha Dcunha, Marius Ringelstein, Eugene May, Caryl Tongco, Marco Pisa, Marta Radaelli, Hadas Stiebel-Kalish, Mark Hellmann, Itay Lotan, Sasitorn Siritho, Jérôme de Seze, Thomas Senger, Caroline Tilikete, Alvaro Cobo Calvo, Denis Bernardi Bichuetti, Ivan Maynart Tavares, Kerstin Soelberg, Ayse Altintas, Rengin Yildirim, Uygur Tanriverdi, Zoe Rimler, Allyson Reid, Yang Mao-Draayer, Ibis Soto de Castillo, Michael R Yeaman, and Terry J Smith

Subjects
Medicine
Abstract

Purpose Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD.Participants The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices.Findings to date The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline.Future plans We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications.

Published
2020
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3. Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders

Author

Maria Isabel Leite, Letizia Leocani, Jérôme De Seze, Denis Bernardi Bichuetti, Ibis Soto de Castillo, Sasitorn Siritho, Alvaro Cobo-Calvo, Elena H. Martinez-Lapiscina, Anitha D'Cunha, Adriana Roca-Fernandez, Jacqueline Palace, Orhan Aktas, Marco Aurélio Lana-Peixoto, Marco Pisa, Michael R. Yeaman, Anu Jacob, Mariana Andrade Fontenelle, Friedemann Paul, Ari J. Green, Yang Mao-Draayer, Eugene F May, Claudia Chien, Alireza Dehghani, Ivan Maynart Tavares, Lawrence J. Cook, Angelo Lu, Su-Kyung Jung, Rengin Yildirim, Ayse Altintas, Mohsen Pourazizi, Ho Jin Kim, Rahele Kafieh, Caryl Tongco, Lekha Pandit, Hadas Stiebel-Kalish, Romain Marignier, Fereshteh Ashtari, Hanna Zimmermann, Joachim Havla, M. Radaelli, Svenja Specovius, Frederike C. Oertel, Kerstin Soelberg, Srilakshmi M Sharma, Axel Petzold, Seyedamirhosein Motamedi, Zoe Rimler, Saif Huda, Philipp Albrecht, Alexander U. Brandt, Jae-Won Hyun, Allyson Reid, Marius Ringelstein, Uygur Tanriverdi, Terry J. Smith, Thomas Senger, Nasrin Asgari, Charlotte Bereuter, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Lu, A., Zimmermann, HG., Specovius, S., Motamedi, S., Chien, C., Bereuter, C., Lana-Peixoto, MA., Fontenelle, MA., Ashtari, F., Kafieh, R., Dehghani, A., Pourazizi, M., Pandit, L., D Cunha, A., Kim, HJ., Hyun, JW., Jung, SK., Leocani, L., Pisa, M., Radaelli, M., Siritho, S., May, E.F., Tongco, C., De Sèze, J., Senger, T., Palace, J., Roca-Fernández, A., Leite, MI., Sharma, SM., Stiebel-Kalish, H., Asgari, N., Soelberg, K.K., Martinez-Lapiscina, EH., Havla, J., Mao-Draayer, Y., Rimler, Z., Reid, A., Marignier, R., Cobo-Calvo, A., Tanriverdi, U., Yildirim, R., Aktas, O., Ringelstein, M., Albrecht, P., Tavares, IM., Bichuetti, DB., Jacob, A., Huda, S., Soto de Castillo, I., Petzold, A., Green, AJ., Yeaman, MR., Smith, TJ., Cook, L., Paul, F., Brandt, AU., Oertel, FC., GJCF International Clinical Consortium for NMOSD., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Neurology, Ophthalmology, APH - Mental Health, APH - Methodology, and Amsterdam Neuroscience - Neuroinfection & -inflammation

Subjects
Adult, Male, medicine.medical_specialty, genetic structures, Vision, Clinical neurology, Ophthalmology, Outer plexiform layer, Retina, chemistry.chemical_compound, medicine, Humans, In patient, Optic neuritis, Outer nuclear layer, Autoantibodies, Aquaporin 4, business.industry, Neuromyelitis Optica, Retinal, Middle Aged, medicine.disease, eye diseases, Neurosciences and neurology, Psychiatry, Surgery, Psychiatry and Mental health, medicine.anatomical_structure, Retinal dysfunction, Cross-Sectional Studies, chemistry, Neuromyelitis Optica Spectrum Disorders, Astrocytes, Female, Neurology (clinical), sense organs, business, Function and Dysfunction of the Nervous System, Axonal degeneration, Tomography, Optical Coherence
Abstract

Background: patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. Method: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. Results: no significant thinning of OPL (25.02 +/- 2.03 mu m) or ONL (61.63 +/- 7.04 mu m) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10 +/- 2.00 mu m; ONL: 64.71 +/- 7.87 mu m) or healthy controls (OPL: 24.58 +/- 1.64 mu m; ONL: 63.59 +/- 5.78 mu m). Eyes of patients who were AQP4-IgG+ (19.84 +/- 5.09 mu m, p=0.027) and MOG-IgG+ (19.82 +/- 4.78 mu m, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99 +/- 5.14 mu m); this was not observed elsewhere. Conclusion: the results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates., Guthy Jackson Charitable Foundation (GJCF); German Research Foundation (DFG)

Published
2021

4. Time to next relapse as a primary endpoint in neuromyelitis optica clinical trials

Author

Anu Jacob, Maria Isabel Leite, J Kitley, Liene Elsone, and Jacqueline Palace

Subjects
medicine.medical_specialty, Neuromyelitis optica, Time Factors, business.industry, Clinical study design, Multiple sclerosis, Neuromyelitis Optica, Azathioprine, medicine.disease, Disease-Free Survival, Clinical trial, Psychiatry and Mental health, Recurrence, Internal medicine, Immunology, medicine, Prednisolone, Clinical endpoint, Humans, Surgery, Rituximab, Neurology (clinical), business, medicine.drug
Abstract

Neuromyelitis optica (NMO) and its spectrum disorder (NMOSD) is a severe autoimmune inflammatory disorder of the central nervous system, with recurrent attacks mainly focused on the optic nerves and spinal cord. Untreated, it has a high morbidity and mortality. Serum aquaporin-4 (AQP4) antibodies are present in the majority of patients, are recognised as pathogenic and are a predictor of further relapses.1 Most specialists treat AQP4 antibody-positive patients early and aggressively with immunosuppression to prevent further attacks. There have been no randomised trials in NMO, but prednisolone, azathioprine, mycophenolate mofetil, methotrexate and rituximab are among the therapies currently used and appear to have comparable efficacy.2 ,3 Because of the potentially devastating nature of NMO relapses, many clinicians would consider a single relapse on treatment to represent treatment failure and an indication to alter therapy, particularly if the relapse is severe and the therapy has had adequate time to work. This alteration can take the form of an increase in dosage of current treatment or a switch to an alternative agent. There is an urgent need to identify the most effective treatment regimens, particularly because there are many novel therapeutic candidates being developed, including those which act on the antibody-producing or complement pathways, and an AQP4 monoclonal antibody blocker.4 Current NMO study designs under discussion vary, with some regulatory authorities requesting placebo comparator arms but others accepting standard treatments (azathioprine or alternative plus low dose oral steroids)3 as comparators either as add-on or …

Published
2016

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