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

Author

Lu, Angelo, Lu, Angelo, Zimmermann, Hanna G, Specovius, Svenja, Motamedi, Seyedamirhosein, Chien, Claudia, Bereuter, Charlotte, Lana-Peixoto, Marco A, Fontenelle, Mariana Andrade, Ashtari, Fereshteh, Kafieh, Rahele, Dehghani, Alireza, Pourazizi, Mohsen, Pandit, Lekha, D'Cunha, Anitha, Kim, Ho Jin, Hyun, Jae-Won, Jung, Su-Kyung, Leocani, Letizia, Pisa, Marco, Radaelli, Marta, Siritho, Sasitorn, May, Eugene F, Tongco, Caryl, De Sèze, Jérôme, Senger, Thomas, Palace, Jacqueline, Roca-Fernández, Adriana, Leite, Maria Isabel, Sharma, Srilakshmi M, Stiebel-Kalish, Hadas, Asgari, Nasrin, Soelberg, Kerstin Kathrine, Martinez-Lapiscina, Elena H, Havla, Joachim, Mao-Draayer, Yang, Rimler, Zoe, Reid, Allyson, Marignier, Romain, Cobo-Calvo, Alvaro, Altintas, Ayse, Tanriverdi, Uygur, Yildirim, Rengin, Aktas, Orhan, Ringelstein, Marius, Albrecht, Philipp, Tavares, Ivan Maynart, Bichuetti, Denis Bernardi, Jacob, Anu, Huda, Saif, Soto de Castillo, Ibis, Petzold, Axel, Green, Ari J, Yeaman, Michael R, Smith, Terry J, Cook, Lawrence, Paul, Friedemann, Brandt, Alexander U, Oertel, Frederike Cosima, GJCF International Clinical Consortium for NMOSD, Lu, Angelo, Lu, Angelo, Zimmermann, Hanna G, Specovius, Svenja, Motamedi, Seyedamirhosein, Chien, Claudia, Bereuter, Charlotte, Lana-Peixoto, Marco A, Fontenelle, Mariana Andrade, Ashtari, Fereshteh, Kafieh, Rahele, Dehghani, Alireza, Pourazizi, Mohsen, Pandit, Lekha, D'Cunha, Anitha, Kim, Ho Jin, Hyun, Jae-Won, Jung, Su-Kyung, Leocani, Letizia, Pisa, Marco, Radaelli, Marta, Siritho, Sasitorn, May, Eugene F, Tongco, Caryl, De Sèze, Jérôme, Senger, Thomas, Palace, Jacqueline, Roca-Fernández, Adriana, Leite, Maria Isabel, Sharma, Srilakshmi M, Stiebel-Kalish, Hadas, Asgari, Nasrin, Soelberg, Kerstin Kathrine, Martinez-Lapiscina, Elena H, Havla, Joachim, Mao-Draayer, Yang, Rimler, Zoe, Reid, Allyson, Marignier, Romain, Cobo-Calvo, Alvaro, Altintas, Ayse, Tanriverdi, Uygur, Yildirim, Rengin, Aktas, Orhan, Ringelstein, Marius, Albrecht, Philipp, Tavares, Ivan Maynart, Bichuetti, Denis Bernardi, Jacob, Anu, Huda, Saif, Soto de Castillo, Ibis, Petzold, Axel, Green, Ari J, Yeaman, Michael R, Smith, Terry J, Cook, Lawrence, Paul, Friedemann, Brandt, Alexander U, Oertel, Frederike Cosima, and GJCF International Clinical Consortium for NMOSD

Abstract

BackgroundPatients 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.Method197 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.ResultsNo significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere.ConclusionThe 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.

Published
2022

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

Author

Lu, Angelo, Lu, Angelo, Zimmermann, Hanna G, Specovius, Svenja, Motamedi, Seyedamirhosein, Chien, Claudia, Bereuter, Charlotte, Lana-Peixoto, Marco A, Fontenelle, Mariana Andrade, Ashtari, Fereshteh, Kafieh, Rahele, Dehghani, Alireza, Pourazizi, Mohsen, Pandit, Lekha, D'Cunha, Anitha, Kim, Ho Jin, Hyun, Jae-Won, Jung, Su-Kyung, Leocani, Letizia, Pisa, Marco, Radaelli, Marta, Siritho, Sasitorn, May, Eugene F, Tongco, Caryl, De Sèze, Jérôme, Senger, Thomas, Palace, Jacqueline, Roca-Fernández, Adriana, Leite, Maria Isabel, Sharma, Srilakshmi M, Stiebel-Kalish, Hadas, Asgari, Nasrin, Soelberg, Kerstin Kathrine, Martinez-Lapiscina, Elena H, Havla, Joachim, Mao-Draayer, Yang, Rimler, Zoe, Reid, Allyson, Marignier, Romain, Cobo-Calvo, Alvaro, Altintas, Ayse, Tanriverdi, Uygur, Yildirim, Rengin, Aktas, Orhan, Ringelstein, Marius, Albrecht, Philipp, Tavares, Ivan Maynart, Bichuetti, Denis Bernardi, Jacob, Anu, Huda, Saif, Soto de Castillo, Ibis, Petzold, Axel, Green, Ari J, Yeaman, Michael R, Smith, Terry J, Cook, Lawrence, Paul, Friedemann, Brandt, Alexander U, Oertel, Frederike Cosima, GJCF International Clinical Consortium for NMOSD, Lu, Angelo, Lu, Angelo, Zimmermann, Hanna G, Specovius, Svenja, Motamedi, Seyedamirhosein, Chien, Claudia, Bereuter, Charlotte, Lana-Peixoto, Marco A, Fontenelle, Mariana Andrade, Ashtari, Fereshteh, Kafieh, Rahele, Dehghani, Alireza, Pourazizi, Mohsen, Pandit, Lekha, D'Cunha, Anitha, Kim, Ho Jin, Hyun, Jae-Won, Jung, Su-Kyung, Leocani, Letizia, Pisa, Marco, Radaelli, Marta, Siritho, Sasitorn, May, Eugene F, Tongco, Caryl, De Sèze, Jérôme, Senger, Thomas, Palace, Jacqueline, Roca-Fernández, Adriana, Leite, Maria Isabel, Sharma, Srilakshmi M, Stiebel-Kalish, Hadas, Asgari, Nasrin, Soelberg, Kerstin Kathrine, Martinez-Lapiscina, Elena H, Havla, Joachim, Mao-Draayer, Yang, Rimler, Zoe, Reid, Allyson, Marignier, Romain, Cobo-Calvo, Alvaro, Altintas, Ayse, Tanriverdi, Uygur, Yildirim, Rengin, Aktas, Orhan, Ringelstein, Marius, Albrecht, Philipp, Tavares, Ivan Maynart, Bichuetti, Denis Bernardi, Jacob, Anu, Huda, Saif, Soto de Castillo, Ibis, Petzold, Axel, Green, Ari J, Yeaman, Michael R, Smith, Terry J, Cook, Lawrence, Paul, Friedemann, Brandt, Alexander U, Oertel, Frederike Cosima, and GJCF International Clinical Consortium for NMOSD

Abstract

BackgroundPatients 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.Method197 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.ResultsNo significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere.ConclusionThe 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.

Published
2022

3. Brain atrophy and lesion burden are associated with disability progression in a multiple sclerosis real-world dataset using only T2-FLAIR: The NeuroSTREAM MSBase study.

Author

UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, Barnett, Michael, Bergsland, Niels, Weinstock-Guttman, Bianca, Butzkueven, Helmut, Kalincik, Tomas, Desmond, Patricia, Gaillard, Frank, van Pesch, Vincent, Ozakbas, Serkan, Rojas, Juan Ignacio, Boz, Cavit, Altintas, Ayse, Wang, Chenyu, Dwyer, Michael G, Yang, Suzie, Jakimovski, Dejan, Kyle, Kain, Ramasamy, Deepa P, Zivadinov, Robert, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, Barnett, Michael, Bergsland, Niels, Weinstock-Guttman, Bianca, Butzkueven, Helmut, Kalincik, Tomas, Desmond, Patricia, Gaillard, Frank, van Pesch, Vincent, Ozakbas, Serkan, Rojas, Juan Ignacio, Boz, Cavit, Altintas, Ayse, Wang, Chenyu, Dwyer, Michael G, Yang, Suzie, Jakimovski, Dejan, Kyle, Kain, Ramasamy, Deepa P, and Zivadinov, Robert

Abstract

Methodological challenges limit the use of brain atrophy and lesion burden measures in the follow-up of multiple sclerosis (MS) patients on clinical routine datasets. To determine the feasibility of T2-FLAIR-only measures of lateral ventricular volume (LVV) and salient central lesion volume (SCLV), as markers of disability progression (DP) in MS. A total of 3,228 MS patients from 9 MSBase centers in 5 countries were enrolled. Of those, 2,875 (218 with clinically isolated syndrome, 2,231 with relapsing-remitting and 426 with progressive disease subtype) fulfilled inclusion and exclusion criteria. Patients were scanned on either 1.5 T or 3 T MRI scanners, and 5,750 brain scans were collected at index and on average after 42.3 months at post-index. Demographic and clinical data were collected from the MSBase registry. LVV and SCLV were measured on clinical routine T2-FLAIR images. Longitudinal LVV and SCLV analyses were successful in 96% of the scans. 57% of patients had scanner-related changes over the follow-up. After correcting for age, sex, disease duration, disability, disease-modifying therapy and LVV at index, and follow-up time, MS patients with DP (n = 671) had significantly greater absolute LVV change compared to stable (n = 1,501) or disability improved (DI, n = 248) MS patients (2.0 mL vs. 1.4 mL vs. 1.1 mL, respectively, ANCOVA p < 0.001, post-hoc pair-wise DP vs. Stable p = 0.003; and DP vs. DI, p = 0.002). Similar ANCOVA model was also significant for SCLV (p = 0.03). LVV-based atrophy and SCLV-based lesion outcomes are feasible on clinically acquired T2-FLAIR scans in a multicenter fashion and are associated with DP over mid-term.

Published
2021

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

Author

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

Abstract

PurposeOptical 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.ParticipantsThe 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 dateThe 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 plansWe 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

5. Sex effects across the lifespan in women with multiple sclerosis.

Author

Krysko, Kristen M, Krysko, Kristen M, Graves, Jennifer S, Dobson, Ruth, Altintas, Ayse, Amato, Maria Pia, Bernard, Jacqueline, Bonavita, Simona, Bove, Riley, Cavalla, Paola, Clerico, Marinella, Corona, Teresa, Doshi, Anisha, Fragoso, Yara, Jacobs, Dina, Jokubaitis, Vilija, Landi, Doriana, Llamosa, Gloria, Longbrake, Erin E, Maillart, Elisabeth, Marta, Monica, Midaglia, Luciana, Shah, Suma, Tintore, Mar, van der Walt, Anneke, Voskuhl, Rhonda, Wang, Yujie, Zabad, Rana K, Zeydan, Burcu, Houtchens, Maria, Hellwig, Kerstin, Krysko, Kristen M, Krysko, Kristen M, Graves, Jennifer S, Dobson, Ruth, Altintas, Ayse, Amato, Maria Pia, Bernard, Jacqueline, Bonavita, Simona, Bove, Riley, Cavalla, Paola, Clerico, Marinella, Corona, Teresa, Doshi, Anisha, Fragoso, Yara, Jacobs, Dina, Jokubaitis, Vilija, Landi, Doriana, Llamosa, Gloria, Longbrake, Erin E, Maillart, Elisabeth, Marta, Monica, Midaglia, Luciana, Shah, Suma, Tintore, Mar, van der Walt, Anneke, Voskuhl, Rhonda, Wang, Yujie, Zabad, Rana K, Zeydan, Burcu, Houtchens, Maria, and Hellwig, Kerstin

Abstract

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.

Published
2020

6. Early clinical markers of aggressive multiple sclerosis.

Author

UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Malpas, Charles B, Manouchehrinia, Ali, Sharmin, Sifat, Roos, Izanne, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Eichau, Sara, Bergamaschi, Roberto, Sola, Patrizia, Ferraro, Diana, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Grand'Maison, Francois, Ozakbas, Serkan, Van Pesch, Vincent, Granella, Franco, Hupperts, Raymond, Pucci, Eugenio, Boz, Cavit, Sidhom, Youssef, Gouider, Riadh, Spitaleri, Daniele, Soysal, Aysun, Petersen, Thor, Verheul, Freek, Karabudak, Rana, Turkoglu, Recai, Ramo-Tello, Cristina, Terzi, Murat, Cristiano, Edgardo, Slee, Mark, McCombe, Pamela, Macdonell, Richard, Fragoso, Yara, Olascoaga, Javier, Altintas, Ayse, Olsson, Tomas, Butzkueven, Helmut, Hillert, Jan, Kalincik, Tomas, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Malpas, Charles B, Manouchehrinia, Ali, Sharmin, Sifat, Roos, Izanne, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Eichau, Sara, Bergamaschi, Roberto, Sola, Patrizia, Ferraro, Diana, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Grand'Maison, Francois, Ozakbas, Serkan, Van Pesch, Vincent, Granella, Franco, Hupperts, Raymond, Pucci, Eugenio, Boz, Cavit, Sidhom, Youssef, Gouider, Riadh, Spitaleri, Daniele, Soysal, Aysun, Petersen, Thor, Verheul, Freek, Karabudak, Rana, Turkoglu, Recai, Ramo-Tello, Cristina, Terzi, Murat, Cristiano, Edgardo, Slee, Mark, McCombe, Pamela, Macdonell, Richard, Fragoso, Yara, Olascoaga, Javier, Altintas, Ayse, Olsson, Tomas, Butzkueven, Helmut, Hillert, Jan, and Kalincik, Tomas

Abstract

Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence

Published
2020

7. Treatment response score to glatiramer acetate or interferon beta-1a.

Author

UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Bovis, Francesca, Kalincik, Tomas, Lublin, Fred, Cutter, Gary, Malpas, Charles, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Onofrj, Marco, Lugaresi, Alessandra, Izquierdo, Guillermo, Eichau, Sara, Patti, Francesco, Terzi, Murat, Grammond, Pierre, Bergamaschi, Roberto, Sola, Patrizia, Ferraro, Diana, Ozakbas, Serkan, Iuliano, Gerardo, Boz, Cavit, Hupperts, Raymond, Grand'Maison, Francois, Oreja-Guevara, Celia, Van Pesch, Vincent, Cartechini, Elisabetta, Petersen, Thor, Altintas, Ayse, Soysal, Aysun, Ramo-Tello, Cristina, McCombe, Pamela, Turkoglu, Recai, Butzkueven, Helmut, Wolinsky, Jerry S, Solaro, Claudio, Sormani, Maria Pia, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Bovis, Francesca, Kalincik, Tomas, Lublin, Fred, Cutter, Gary, Malpas, Charles, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Onofrj, Marco, Lugaresi, Alessandra, Izquierdo, Guillermo, Eichau, Sara, Patti, Francesco, Terzi, Murat, Grammond, Pierre, Bergamaschi, Roberto, Sola, Patrizia, Ferraro, Diana, Ozakbas, Serkan, Iuliano, Gerardo, Boz, Cavit, Hupperts, Raymond, Grand'Maison, Francois, Oreja-Guevara, Celia, Van Pesch, Vincent, Cartechini, Elisabetta, Petersen, Thor, Altintas, Ayse, Soysal, Aysun, Ramo-Tello, Cristina, McCombe, Pamela, Turkoglu, Recai, Butzkueven, Helmut, Wolinsky, Jerry S, Solaro, Claudio, and Sormani, Maria Pia

Abstract

OBJECTIVE: To compare the effectiveness of glatiramer acetate (GA) vs intra-muscular Interferon beta-1a (IFNbeta-1a)), we applied a previously published statistical method, aimed at identifying patients' profiles associated with efficacy of treatments. METHODS: Data from 2 independent multiple sclerosis datasets, a randomized study (the CombiRx trial, evaluating GA vs IFNbeta-1a and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors. RESULTS: The overall ARR ratio of GA vs IFNbeta-1a in the CombiRx trial was 0.72. The response score (made up of a linear combination of age, sex, relapses in the previous year, disease duration and EDSS) detected differential response of GA vs IFNbeta-1a: in the trial, patients with the largest benefit from GA vs IFNbeta-1a (lower score quartile) had an ARR ratio of 0.40 (95%confidence interval [CI] = 0.25-0.63), those in the 2 middle quartiles of 0.90 (95% CI = 0.61-1.34) and those in the upper quartile of 1.14 (95%CI = 0.59-2.18) (heterogeneity p = 0.012); this result was validated on MSbase, with the corresponding ARR ratios of 0.58 (95% CI = 0.46-0.72), 0.92 (95% CI = 0.77-1.09) and 1.29 (95% CI = 0.97-1.71); heterogeneity p < 0.0001). CONCLUSIONS: We demonstrate the possibility of a criterion, based on patients' characteristics, to choose whether to treat with GA or IFNbeta-1a. This result, replicated on an independent real-life cohort, may have implications for clinical decisions in everyday clinical practice.

Published
2020

8. Risk of secondary progressive multiple sclerosis: A longitudinal study.

Author

UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Fambiatos, Adam, Jokubaitis, Vilija, Horakova, Dana, Kubala Havrdova, Eva, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Lugaresi, Alessandra, Izquierdo, Guillermo, Grand'Maison, Francois, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Alroughani, Raed, Terzi, Murat, Hupperts, Raymond, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Bergamaschi, Roberto, Van Pesch, Vincent, Ozakbas, Serkan, Granella, Franco, Turkoglu, Recai, Iuliano, Gerardo, Spitaleri, Daniele, McCombe, Pamela, Solaro, Claudio, Slee, Mark, Ampapa, Radek, Soysal, Aysun, Petersen, Thor, Sanchez-Menoyo, Jose Luis, Verheul, Freek, Prevost, Julie, Sidhom, Youssef, Van Wijmeersch, Bart, Vucic, Steve, Cristiano, Edgardo, Saladino, Maria Laura, Deri, Norma, Barnett, Michael, Olascoaga, Javier, Moore, Fraser, Skibina, Olga, Gray, Orla, Fragoso, Yara, Yamout, Bassem, Shaw, Cameron, Singhal, Bhim, Shuey, Neil, Hodgkinson, Suzanne, Altintas, Ayse, Al-Harbi, Talal, Csepany, Tunde, Taylor, Bruce, Hughes, Jordana, Jun, Jae-Kwan, van der Walt, Anneke, Spelman, Tim, Butzkueven, Helmut, Kalincik, Tomas, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Fambiatos, Adam, Jokubaitis, Vilija, Horakova, Dana, Kubala Havrdova, Eva, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Lugaresi, Alessandra, Izquierdo, Guillermo, Grand'Maison, Francois, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Alroughani, Raed, Terzi, Murat, Hupperts, Raymond, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Bergamaschi, Roberto, Van Pesch, Vincent, Ozakbas, Serkan, Granella, Franco, Turkoglu, Recai, Iuliano, Gerardo, Spitaleri, Daniele, McCombe, Pamela, Solaro, Claudio, Slee, Mark, Ampapa, Radek, Soysal, Aysun, Petersen, Thor, Sanchez-Menoyo, Jose Luis, Verheul, Freek, Prevost, Julie, Sidhom, Youssef, Van Wijmeersch, Bart, Vucic, Steve, Cristiano, Edgardo, Saladino, Maria Laura, Deri, Norma, Barnett, Michael, Olascoaga, Javier, Moore, Fraser, Skibina, Olga, Gray, Orla, Fragoso, Yara, Yamout, Bassem, Shaw, Cameron, Singhal, Bhim, Shuey, Neil, Hodgkinson, Suzanne, Altintas, Ayse, Al-Harbi, Talal, Csepany, Tunde, Taylor, Bruce, Hughes, Jordana, Jun, Jae-Kwan, van der Walt, Anneke, Spelman, Tim, Butzkueven, Helmut, and Kalincik, Tomas

Abstract

BACKGROUND: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested. OBJECTIVE: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis. METHODS: Patients with adult-onset relapsing-remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed. RESULTS: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p < 0.001), longer disease duration (HR = 1.01, p = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30, p < 0.001), more rapid disability trajectory (HR = 2.82, p < 0.001) and greater number of relapses in the previous year (HR = 1.07, p = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62, p = 0.039) and disease-modifying therapy exposure (HR = 0.71, p = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion. CONCLUSION: Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.

Published
2020

9. Sex effects across the lifespan in women with multiple sclerosis.

Author

Krysko, Kristen M, Krysko, Kristen M, Graves, Jennifer S, Dobson, Ruth, Altintas, Ayse, Amato, Maria Pia, Bernard, Jacqueline, Bonavita, Simona, Bove, Riley, Cavalla, Paola, Clerico, Marinella, Corona, Teresa, Doshi, Anisha, Fragoso, Yara, Jacobs, Dina, Jokubaitis, Vilija, Landi, Doriana, Llamosa, Gloria, Longbrake, Erin E, Maillart, Elisabeth, Marta, Monica, Midaglia, Luciana, Shah, Suma, Tintore, Mar, van der Walt, Anneke, Voskuhl, Rhonda, Wang, Yujie, Zabad, Rana K, Zeydan, Burcu, Houtchens, Maria, Hellwig, Kerstin, Krysko, Kristen M, Krysko, Kristen M, Graves, Jennifer S, Dobson, Ruth, Altintas, Ayse, Amato, Maria Pia, Bernard, Jacqueline, Bonavita, Simona, Bove, Riley, Cavalla, Paola, Clerico, Marinella, Corona, Teresa, Doshi, Anisha, Fragoso, Yara, Jacobs, Dina, Jokubaitis, Vilija, Landi, Doriana, Llamosa, Gloria, Longbrake, Erin E, Maillart, Elisabeth, Marta, Monica, Midaglia, Luciana, Shah, Suma, Tintore, Mar, van der Walt, Anneke, Voskuhl, Rhonda, Wang, Yujie, Zabad, Rana K, Zeydan, Burcu, Houtchens, Maria, and Hellwig, Kerstin

Abstract

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.

Published
2020

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

Author

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

Abstract

PurposeOptical 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.ParticipantsThe 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 dateThe 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 plansWe 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

11. Collaborative international research in clinical and longitudinal experience study in NMOSD

Author

Ayşe Altıntaş ( ORCID 0000-0002-8524-5087 & YÖK ID 11611), Cook, Lawrence J.; Rose, John W.; Alvey, Jessica S.; Jolley, Anna Marie; Kuhn, Renee; Marron, Brie; Pederson, Melissa; Enriquez, Rene; Yearley, Jeff; McKechnie, Stephen; Han, May H.; Tomczak, Anna J.; Levy, Michael; Mealy, Maureen A.; Coleman, Jessica; Bennett, Jeffrey L.; Johnson, Ruth; Barnes-Garcia, Myka; Traboulsee, Anthony L.; Carruthers, Robert L.; Lee, Lisa Eunyoung; Schubert, Julia J.; McMullen, Katrina; Kister, Ilya; Rimler, Zoe; Reid, Allyson; Sicotte, Nancy L.; Planchon, Sarah M.; Cohen, Jeffrey A.; Ivancic, Diane; Sedlak, Jennifer L.; Sand, Ilana Katz; Repovic, Pavle; Amezcua, Lilyana; Pruitt, Ana; Amundson, Erika; Chitnis, Tanuja; Mullin, Devin S.; Klawiter, Eric C.; Russo, Andrew W.; Riley, Claire S.; Onomichi, Kaho B.; Levine, Libby; Nelson, Katherine E.; Nealon, Nancy M.; Engel, Casey; Kruse-Hoyer, Mason; Marcille, Melanie; Tornes, Leticia; Rumpf, Anne; Greer, Angela; Behne, Megan Kenneally; Rodriguez, Renee R.; Behne, Daniel W.; Blackway, Derek W.; Coords, Brian; Blaschke, Terrence F.; Sheard, Judy; Smith, Terry J.; Behne, Jacinta M.; Yeaman, Michael R.; Abboud, Hesham; Aktas, Orhan; Altintas, Ayse; Apiwattanakul, Metha; Asgari, Nasrin; Banwell, Brenda; Bichuetti, Denis; Bowen, James; Broadley, Simon; Bruck, Wolfgang; Cabre, Philippe; Cohen, Jeffrey; De Seze, Jerome; Delgado-Garcia, Guillermo; Basuroski, Irena Dujmovic; Fujihara, Kazuo; Goodman, Andrew; Havla, Joachim; Hellwig, Kerstin; Hintzen, Rogier; Hooper, D. Craig; Iorio, Raffaele; Jacob, Anu; Jarius, Sven; Jimenez Arango, Jorge Andres; John, Gareth; Kim, Ho Jin; Kim, Sung Min; Kimbrough, Dorian J.; Kissani, Najib; Kleiter, Ingo; Lana-Peixoto, Marco; Leite, M. Isabel; Liu, Yaou; Lublin, Fred; Maiga, Youssoufa; Mao-Draayer, Yang; Marignier, Romain; Matiello, Marcelo; Momtazee, Callene; Morrow, Mark; Nakashima, Ichiro; O'Connor, Kevin; Oreja-Guevara, Celia; Palace, Jacqueline; Pandit, Lekha; Paul, Friedemann; Prayoonwiwat, Naraporn; Probstel, Anne-Katrin; Qian, Peiqing; Quan, Chao; Ringelstein, School of Medicine, Department of Neurology, Ayşe Altıntaş ( ORCID 0000-0002-8524-5087 & YÖK ID 11611), Cook, Lawrence J.; Rose, John W.; Alvey, Jessica S.; Jolley, Anna Marie; Kuhn, Renee; Marron, Brie; Pederson, Melissa; Enriquez, Rene; Yearley, Jeff; McKechnie, Stephen; Han, May H.; Tomczak, Anna J.; Levy, Michael; Mealy, Maureen A.; Coleman, Jessica; Bennett, Jeffrey L.; Johnson, Ruth; Barnes-Garcia, Myka; Traboulsee, Anthony L.; Carruthers, Robert L.; Lee, Lisa Eunyoung; Schubert, Julia J.; McMullen, Katrina; Kister, Ilya; Rimler, Zoe; Reid, Allyson; Sicotte, Nancy L.; Planchon, Sarah M.; Cohen, Jeffrey A.; Ivancic, Diane; Sedlak, Jennifer L.; Sand, Ilana Katz; Repovic, Pavle; Amezcua, Lilyana; Pruitt, Ana; Amundson, Erika; Chitnis, Tanuja; Mullin, Devin S.; Klawiter, Eric C.; Russo, Andrew W.; Riley, Claire S.; Onomichi, Kaho B.; Levine, Libby; Nelson, Katherine E.; Nealon, Nancy M.; Engel, Casey; Kruse-Hoyer, Mason; Marcille, Melanie; Tornes, Leticia; Rumpf, Anne; Greer, Angela; Behne, Megan Kenneally; Rodriguez, Renee R.; Behne, Daniel W.; Blackway, Derek W.; Coords, Brian; Blaschke, Terrence F.; Sheard, Judy; Smith, Terry J.; Behne, Jacinta M.; Yeaman, Michael R.; Abboud, Hesham; Aktas, Orhan; Altintas, Ayse; Apiwattanakul, Metha; Asgari, Nasrin; Banwell, Brenda; Bichuetti, Denis; Bowen, James; Broadley, Simon; Bruck, Wolfgang; Cabre, Philippe; Cohen, Jeffrey; De Seze, Jerome; Delgado-Garcia, Guillermo; Basuroski, Irena Dujmovic; Fujihara, Kazuo; Goodman, Andrew; Havla, Joachim; Hellwig, Kerstin; Hintzen, Rogier; Hooper, D. Craig; Iorio, Raffaele; Jacob, Anu; Jarius, Sven; Jimenez Arango, Jorge Andres; John, Gareth; Kim, Ho Jin; Kim, Sung Min; Kimbrough, Dorian J.; Kissani, Najib; Kleiter, Ingo; Lana-Peixoto, Marco; Leite, M. Isabel; Liu, Yaou; Lublin, Fred; Maiga, Youssoufa; Mao-Draayer, Yang; Marignier, Romain; Matiello, Marcelo; Momtazee, Callene; Morrow, Mark; Nakashima, Ichiro; O'Connor, Kevin; Oreja-Guevara, Celia; Palace, Jacqueline; Pandit, Lekha; Paul, Friedemann; Prayoonwiwat, Naraporn; Probstel, Anne-Katrin; Qian, Peiqing; Quan, Chao; Ringelstein, School of Medicine, and Department of Neurology

Abstract

Objective to develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods to illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results as of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD., The Guthy-Jackson Charitable Foundation, The CIRCLES Project

Published
2019

12. Association of inflammation and disability accrual in patients with progressive-onset multiple sclerosis

Author

Hughes, Jordana, Jokubaitis, Vilija, Lugaresi, Alessandra, Hupperts, Raymond, Izquierdo, Guillermo, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grand'maison, Francois, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Ramo-Tello, Cristina, Trojano, Maria, Slee, Mark, Shaygannejad, Vahid, Boz, Cavit, Lechner-Scott, Jeanette, Van Pesch, Vincent, Pucci, Eugenio, Solaro, Claudio, Verheul, Freek, Terzi, Murat, Granella, Franco, Spitaleri, Daniele, Alroughani, Raed, Jun, Jae-Kwan, Fambiatos, Adam, Van Der Walt, Anneke, Butzkueven, Helmut, Kalincik, Tomas, De Luca, Giovanna, Di Tommaso, Valeria, Travaglini, Daniela, Pietrolongo, Erika, Di Ioia, Maria, Farina, Deborah, Mancinelli, Luca, Vitetta, Francesca, Simone, Anna Maria, Haartsen, Jodi, Spelman, Tim, Marriott, Mark, Kilpatrick, Trevor, King, John, Buzzard, Katherine, Nguyen, Ai-Lan, Dwyer, Chris, Monif, Mastura, Brown, J William L, Kunchok, Amy, Diamanti, Matteo, Cartechini, Elisabetta, Curti, Erica, Tsantes, Elena, Zwanikken, Cees, Rio, Maria Edite, Hughes, Stella, Amato, Maria Pita, Van Wijmeersch, Bart, Sanchez-Menoyo, Jose Luis, Bolaños, Ricardo Fernandez, Sajedi, Seyed Aidin, Iuliano, Gerardo, Den Braber-Moerland, Leontien, Prevost, Julie, Sempere, Angel Perez, Sidhom, Youssef, Butler, Ernest, Vucic, Steve, Taylor, Bruce, Cabrera-Gomez, Jose Antonio, Oreja-Guevara, Celia, Bergamaschi, Roberto, Turkoglu, Recai, Olascoaga, Javier, Cristiano, Edgardo, Rojas, Juan Ingacio, Hodgkinson, Suzanne, Skibina, Olga, Al-Harbi, Talal, Altintas, Ayse, McCombe, Pamela, Sinnige, LGF, Ozakbas, Serken, Saladino, Maria Laura, Bacile, Elizabeth Alejandra, Vrech, Carlos, Shaw, Cameron, Hughes, Jordana, Jokubaitis, Vilija, Lugaresi, Alessandra, Hupperts, Raymond, Izquierdo, Guillermo, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grand'maison, Francois, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Ramo-Tello, Cristina, Trojano, Maria, Slee, Mark, Shaygannejad, Vahid, Boz, Cavit, Lechner-Scott, Jeanette, Van Pesch, Vincent, Pucci, Eugenio, Solaro, Claudio, Verheul, Freek, Terzi, Murat, Granella, Franco, Spitaleri, Daniele, Alroughani, Raed, Jun, Jae-Kwan, Fambiatos, Adam, Van Der Walt, Anneke, Butzkueven, Helmut, Kalincik, Tomas, De Luca, Giovanna, Di Tommaso, Valeria, Travaglini, Daniela, Pietrolongo, Erika, Di Ioia, Maria, Farina, Deborah, Mancinelli, Luca, Vitetta, Francesca, Simone, Anna Maria, Haartsen, Jodi, Spelman, Tim, Marriott, Mark, Kilpatrick, Trevor, King, John, Buzzard, Katherine, Nguyen, Ai-Lan, Dwyer, Chris, Monif, Mastura, Brown, J William L, Kunchok, Amy, Diamanti, Matteo, Cartechini, Elisabetta, Curti, Erica, Tsantes, Elena, Zwanikken, Cees, Rio, Maria Edite, Hughes, Stella, Amato, Maria Pita, Van Wijmeersch, Bart, Sanchez-Menoyo, Jose Luis, Bolaños, Ricardo Fernandez, Sajedi, Seyed Aidin, Iuliano, Gerardo, Den Braber-Moerland, Leontien, Prevost, Julie, Sempere, Angel Perez, Sidhom, Youssef, Butler, Ernest, Vucic, Steve, Taylor, Bruce, Cabrera-Gomez, Jose Antonio, Oreja-Guevara, Celia, Bergamaschi, Roberto, Turkoglu, Recai, Olascoaga, Javier, Cristiano, Edgardo, Rojas, Juan Ingacio, Hodgkinson, Suzanne, Skibina, Olga, Al-Harbi, Talal, Altintas, Ayse, McCombe, Pamela, Sinnige, LGF, Ozakbas, Serken, Saladino, Maria Laura, Bacile, Elizabeth Alejandra, Vrech, Carlos, and Shaw, Cameron

Published
2018

13. Neurofilament ELISA validation

Author

Petzold, Axel, Altintas, Ayse, Andreoni, Laura, Bartos, Ales, Berthele, Achim, Blankenstein, Marinus A, Buee, Luc, Castellazzi, Massimiliano, Cepok, Sabine, Comabella, Manuel, Constantinescu, Cris S, Deisenhammer, Florian, Deniz, Gunnur, Erten, Gaye, Espiño, Mercedes, Fainardi, Enrico, Franciotta, Diego, Freedman, Mark S, Giedraitis, Vilmantas, Gilhus, Nils Erik, Giovannoni, Gavin, Glabinski, Andrzej, Grieb, Pawel, Hartung, Hans-Peter, Hemmer, Bernhard, Herukka, Sanna-Kaisa, Hintzen, Rogier, Ingelsson, Martin, Jackson, Samuel, Jacobsen, Steve, Jafari, Naghmeh, Jalosinski, Marcin, Jarius, Sven, Kapaki, Elisabeth, Kieseier, Bernd C, Koel-Simmelink, Marleen J A, Kornhuber, Johannes, Kuhle, Jens, Kurzepa, Jacek, Lalive, Patrice H, Lannfelt, Lars, Lehmensiek, Vera, Lewczuk, Piotr, Livrea, Paolo, Marnetto, Fabiana, Martino, Davide, Menge, Til, Norgren, Niklas, Papuć, Eva, Paraskevas, George P, Pirttilä, Tuula, Rajda, Cecília, Rejdak, Konrad, Ricny, Jan, Ripova, Daniela, Rosengren, Lars, Ruggieri, Maddalena, Schraen, Susanna, Shaw, Gerry, Sindic, Christian, Siva, Aksel, Stigbrand, Torgny, Stonebridge, Iva, Topcular, Baris, Trojano, Maria, Tumani, Hayrettin, Twaalfhoven, Harry A M, Vécsei, László, Van Pesch, Vincent, Vanderstichele, Hugo, Vedeler, Christian, Verbeek, Marcel M, Villar, Luisa Maria, Weissert, Robert, Wildemann, Brigitte, Yang, Cui, Yao, Karen, Teunissen, Charlotte E, Petzold, Axel, Altintas, Ayse, Andreoni, Laura, Bartos, Ales, Berthele, Achim, Blankenstein, Marinus A, Buee, Luc, Castellazzi, Massimiliano, Cepok, Sabine, Comabella, Manuel, Constantinescu, Cris S, Deisenhammer, Florian, Deniz, Gunnur, Erten, Gaye, Espiño, Mercedes, Fainardi, Enrico, Franciotta, Diego, Freedman, Mark S, Giedraitis, Vilmantas, Gilhus, Nils Erik, Giovannoni, Gavin, Glabinski, Andrzej, Grieb, Pawel, Hartung, Hans-Peter, Hemmer, Bernhard, Herukka, Sanna-Kaisa, Hintzen, Rogier, Ingelsson, Martin, Jackson, Samuel, Jacobsen, Steve, Jafari, Naghmeh, Jalosinski, Marcin, Jarius, Sven, Kapaki, Elisabeth, Kieseier, Bernd C, Koel-Simmelink, Marleen J A, Kornhuber, Johannes, Kuhle, Jens, Kurzepa, Jacek, Lalive, Patrice H, Lannfelt, Lars, Lehmensiek, Vera, Lewczuk, Piotr, Livrea, Paolo, Marnetto, Fabiana, Martino, Davide, Menge, Til, Norgren, Niklas, Papuć, Eva, Paraskevas, George P, Pirttilä, Tuula, Rajda, Cecília, Rejdak, Konrad, Ricny, Jan, Ripova, Daniela, Rosengren, Lars, Ruggieri, Maddalena, Schraen, Susanna, Shaw, Gerry, Sindic, Christian, Siva, Aksel, Stigbrand, Torgny, Stonebridge, Iva, Topcular, Baris, Trojano, Maria, Tumani, Hayrettin, Twaalfhoven, Harry A M, Vécsei, László, Van Pesch, Vincent, Vanderstichele, Hugo, Vedeler, Christian, Verbeek, Marcel M, Villar, Luisa Maria, Weissert, Robert, Wildemann, Brigitte, Yang, Cui, Yao, Karen, and Teunissen, Charlotte E

Abstract

BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. RESULTS: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R=0.60, p<0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R=0.98, p<0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics. CONCLUSION: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.

Published
2010
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14. Neurofilament ELISA validation

Author

Petzold, Axel, Altintas, Ayse, Andreoni, Laura, Bartos, Ales, Berthele, Achim, Blankenstein, Marinus A, Buee, Luc, Castellazzi, Massimiliano, Cepok, Sabine, Comabella, Manuel, Constantinescu, Cris S, Deisenhammer, Florian, Deniz, Gunnur, Erten, Gaye, Espiño, Mercedes, Fainardi, Enrico, Franciotta, Diego, Freedman, Mark S, Giedraitis, Vilmantas, Gilhus, Nils Erik, Giovannoni, Gavin, Glabinski, Andrzej, Grieb, Pawel, Hartung, Hans-Peter, Hemmer, Bernhard, Herukka, Sanna-Kaisa, Hintzen, Rogier, Ingelsson, Martin, Jackson, Samuel, Jacobsen, Steve, Jafari, Naghmeh, Jalosinski, Marcin, Jarius, Sven, Kapaki, Elisabeth, Kieseier, Bernd C, Koel-Simmelink, Marleen J A, Kornhuber, Johannes, Kuhle, Jens, Kurzepa, Jacek, Lalive, Patrice H, Lannfelt, Lars, Lehmensiek, Vera, Lewczuk, Piotr, Livrea, Paolo, Marnetto, Fabiana, Martino, Davide, Menge, Til, Norgren, Niklas, Papuć, Eva, Paraskevas, George P, Pirttilä, Tuula, Rajda, Cecília, Rejdak, Konrad, Ricny, Jan, Ripova, Daniela, Rosengren, Lars, Ruggieri, Maddalena, Schraen, Susanna, Shaw, Gerry, Sindic, Christian, Siva, Aksel, Stigbrand, Torgny, Stonebridge, Iva, Topcular, Baris, Trojano, Maria, Tumani, Hayrettin, Twaalfhoven, Harry A M, Vécsei, László, Van Pesch, Vincent, Vanderstichele, Hugo, Vedeler, Christian, Verbeek, Marcel M, Villar, Luisa Maria, Weissert, Robert, Wildemann, Brigitte, Yang, Cui, Yao, Karen, Teunissen, Charlotte E, Petzold, Axel, Altintas, Ayse, Andreoni, Laura, Bartos, Ales, Berthele, Achim, Blankenstein, Marinus A, Buee, Luc, Castellazzi, Massimiliano, Cepok, Sabine, Comabella, Manuel, Constantinescu, Cris S, Deisenhammer, Florian, Deniz, Gunnur, Erten, Gaye, Espiño, Mercedes, Fainardi, Enrico, Franciotta, Diego, Freedman, Mark S, Giedraitis, Vilmantas, Gilhus, Nils Erik, Giovannoni, Gavin, Glabinski, Andrzej, Grieb, Pawel, Hartung, Hans-Peter, Hemmer, Bernhard, Herukka, Sanna-Kaisa, Hintzen, Rogier, Ingelsson, Martin, Jackson, Samuel, Jacobsen, Steve, Jafari, Naghmeh, Jalosinski, Marcin, Jarius, Sven, Kapaki, Elisabeth, Kieseier, Bernd C, Koel-Simmelink, Marleen J A, Kornhuber, Johannes, Kuhle, Jens, Kurzepa, Jacek, Lalive, Patrice H, Lannfelt, Lars, Lehmensiek, Vera, Lewczuk, Piotr, Livrea, Paolo, Marnetto, Fabiana, Martino, Davide, Menge, Til, Norgren, Niklas, Papuć, Eva, Paraskevas, George P, Pirttilä, Tuula, Rajda, Cecília, Rejdak, Konrad, Ricny, Jan, Ripova, Daniela, Rosengren, Lars, Ruggieri, Maddalena, Schraen, Susanna, Shaw, Gerry, Sindic, Christian, Siva, Aksel, Stigbrand, Torgny, Stonebridge, Iva, Topcular, Baris, Trojano, Maria, Tumani, Hayrettin, Twaalfhoven, Harry A M, Vécsei, László, Van Pesch, Vincent, Vanderstichele, Hugo, Vedeler, Christian, Verbeek, Marcel M, Villar, Luisa Maria, Weissert, Robert, Wildemann, Brigitte, Yang, Cui, Yao, Karen, and Teunissen, Charlotte E

Abstract

This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.

Published
2010
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15. Neurofilament ELISA validation.

Author

UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Petzold, Axel, Altintas, Ayse, Andreoni, Laura, Bartos, Ales, Berthele, Achim, Blankenstein, Marinus A, Buee, Luc, Castellazzi, Massimiliano, Cepok, Sabine, Comabella, Manuel, Constantinescu, Cris S, Deisenhammer, Florian, Deniz, Gunnur, Erten, Gaye, Espiño, Mercedes, Fainardi, Enrico, Franciotta, Diego, Freedman, Mark S, Giedraitis, Vilmantas, Gilhus, Nils Erik, Giovannoni, Gavin, Glabinski, Andrzej, Grieb, Pawel, Hartung, Hans-Peter, Hemmer, Bernhard, Herukka, Sanna-Kaisa, Hintzen, Rogier, Ingelsson, Martin, Jackson, Samuel, Jacobsen, Steve, Jafari, Naghmeh, Jalosinski, Marcin, Jarius, Sven, Kapaki, Elisabeth, Kieseier, Bernd C, Koel-Simmelink, Marleen J A, Kornhuber, Johannes, Kuhle, Jens, Kurzepa, Jacek, Lalive, Patrice H, Lannfelt, Lars, Lehmensiek, Vera, Lewczuk, Piotr, Livrea, Paolo, Marnetto, Fabiana, Martino, Davide, Menge, Til, Norgren, Niklas, Papuć, Eva, Paraskevas, George P, Pirttilä, Tuula, Rajda, Cecília, Rejdak, Konrad, Ricny, Jan, Ripova, Daniela, Rosengren, Lars, Ruggieri, Maddalena, Schraen, Susanna, Shaw, Gerry, Sindic, Christian, Siva, Aksel, Stigbrand, Torgny, Stonebridge, Iva, Topcular, Baris, Trojano, Maria, Tumani, Hayrettin, Twaalfhoven, Harry A M, Vécsei, László, Van Pesch, Vincent, Vanderstichele, Hugo, Vedeler, Christian, Verbeek, Marcel M, Villar, Luisa Maria, Weissert, Robert, Wildemann, Brigitte, Yang, Cui, Yao, Karen, Teunissen, Charlotte E, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Petzold, Axel, Altintas, Ayse, Andreoni, Laura, Bartos, Ales, Berthele, Achim, Blankenstein, Marinus A, Buee, Luc, Castellazzi, Massimiliano, Cepok, Sabine, Comabella, Manuel, Constantinescu, Cris S, Deisenhammer, Florian, Deniz, Gunnur, Erten, Gaye, Espiño, Mercedes, Fainardi, Enrico, Franciotta, Diego, Freedman, Mark S, Giedraitis, Vilmantas, Gilhus, Nils Erik, Giovannoni, Gavin, Glabinski, Andrzej, Grieb, Pawel, Hartung, Hans-Peter, Hemmer, Bernhard, Herukka, Sanna-Kaisa, Hintzen, Rogier, Ingelsson, Martin, Jackson, Samuel, Jacobsen, Steve, Jafari, Naghmeh, Jalosinski, Marcin, Jarius, Sven, Kapaki, Elisabeth, Kieseier, Bernd C, Koel-Simmelink, Marleen J A, Kornhuber, Johannes, Kuhle, Jens, Kurzepa, Jacek, Lalive, Patrice H, Lannfelt, Lars, Lehmensiek, Vera, Lewczuk, Piotr, Livrea, Paolo, Marnetto, Fabiana, Martino, Davide, Menge, Til, Norgren, Niklas, Papuć, Eva, Paraskevas, George P, Pirttilä, Tuula, Rajda, Cecília, Rejdak, Konrad, Ricny, Jan, Ripova, Daniela, Rosengren, Lars, Ruggieri, Maddalena, Schraen, Susanna, Shaw, Gerry, Sindic, Christian, Siva, Aksel, Stigbrand, Torgny, Stonebridge, Iva, Topcular, Baris, Trojano, Maria, Tumani, Hayrettin, Twaalfhoven, Harry A M, Vécsei, László, Van Pesch, Vincent, Vanderstichele, Hugo, Vedeler, Christian, Verbeek, Marcel M, Villar, Luisa Maria, Weissert, Robert, Wildemann, Brigitte, Yang, Cui, Yao, Karen, and Teunissen, Charlotte E

Abstract

This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.

Published
2010

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