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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, 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, de Castillo, Ibis Soto, Petzold, Axel, Green, Ari J, Yeaman, Michael R, Smith, Terry J, Cook, Lawrence, Paul, Friedemann, Brandt, Alexander U, and Oertel, Frederike Cosima

Subjects
Eye Disease and Disorders of Vision, Brain Disorders, Neurosciences, Neurodegenerative, Adult, Aquaporin 4, Astrocytes, Autoantibodies, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Neuromyelitis Optica, Retina, Tomography, Optical Coherence, vision, clinical neurology, ophthalmology, GJCF International Clinical Consortium for NMOSD, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
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. Retinal Optical Coherence Tomography in Neuromyelitis Optica.

Author

Oertel, Frederike, Specovius, Svenja, Zimmermann, Hanna, Chien, Claudia, Motamedi, Seyedamirhosein, Bereuter, Charlotte, Cook, Lawrence, Lana Peixoto, Marco, Fontanelle, Mariana, Kim, Ho, Hyun, Jae-Won, Palace, Jacqueline, Roca-Fernandez, Adriana, Leite, Maria, Sharma, Srilakshmi, Ashtari, Fereshteh, 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, Stiebel-Kalish, Hadas, Siritho, Sasitorn, de Seze, Jérome, Senger, Thomas, Havla, Joachim, Marignier, Romain, Cobo-Calvo, Alvaro, Bichuetti, Denis, Tavares, Ivan, Asgari, Nasrin, Soelberg, Kerstin, Altintas, Ayse, Yildirim, Rengin, Tanriverdi, Uygur, Jacob, Anu, Huda, Saif, Rimler, Zoe, Reid, Allyson, Mao-Draayer, Yang, Soto de Castillo, Ibis, Petzold, Axel, Green, Ari, Yeaman, Michael, Smith, Terry, Brandt, Alexander, and Paul, Friedemann

Subjects
Adult, Aquaporin 4, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Neuromyelitis Optica, Optic Neuritis, Retinal Neurons, Retrospective Studies, Tomography, Optical Coherence, Young Adult
Abstract

BACKGROUND AND OBJECTIVES: To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts. METHODS: The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG-seropositive patients with NMOSD and 72 healthy controls (HCs). Participants underwent OCT with central reading including quality control and intraretinal segmentation. The primary outcome was thickness of combined ganglion cell and inner plexiform (GCIP) layer; secondary outcomes were thickness of peripapillary retinal nerve fiber layer (pRNFL) and visual acuity (VA). RESULTS: Eyes with ON (NMOSD-ON, N = 260) or without ON (NMOSD-NON, N = 241) were assessed compared with HCs (N = 136). In NMOSD-ON, GCIP layer (57.4 ± 12.2 μm) was reduced compared with HC (GCIP layer: 81.4 ± 5.7 μm, p < 0.001). GCIP layer loss (-22.7 μm) after the first ON was higher than after the next (-3.5 μm) and subsequent episodes. pRNFL observations were similar. NMOSD-NON exhibited reduced GCIP layer but not pRNFL compared with HC. VA was greatly reduced in NMOSD-ON compared with HC eyes, but did not differ between NMOSD-NON and HC. DISCUSSION: Our results emphasize that attack prevention is key to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies ameliorating attack-related damage, especially during a first attack, are an unmet clinical need. Mild signs of neuroaxonal changes without apparent vision loss in ON-unaffected eyes might be solely due to contralateral ON attacks and do not suggest clinically relevant progression but need further investigation.

Published
2021

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

Author

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

Subjects
GJCF International Clinical Consortium for NMOSD, medical retina, neuro-ophthalmology, neurology, radiology & imaging, radiology &amp, imaging, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
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

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

Author

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

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Neurosciences, Contraception/Reproduction, Aging, Neurodegenerative, Multiple Sclerosis, Prevention, Autoimmune Disease, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Reproductive health and childbirth, Good Health and Well Being, breastfeeding, multiple sclerosis, pregnancy, sex differences, sex hormones, women
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

5. State of the Art and Future Challenges in Multiple Sclerosis Research and Medical Management: An Insight into the 5th International Porto Congress of Multiple Sclerosis

Author

Sá, María José, Soares dos Reis, Ricardo, Altintas, Ayse, Celius, Elisabeth Gulowsen, Chien, Claudia, Comi, Giancarlo, Graus, Francesc, Hillert, Jan, Hobart, Jeremy, Khan, Gulfaraz, Kissani, Najib, Langdon, Dawn, Leite, Maria Isabel, Okuda, Darin T., Palace, Jacqueline, Papais-Alvarenga, Regina María, Mendes-Pinto, Inês, and Shi, Fu-Dong

Published
2020
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6. Nonisolated forms of rational triple point singularities of surfaces and their resolutions

Author

Altintas, Ayse, Cevik, Gulen, and Tosun, Meral

Subjects
Mathematics - Algebraic Geometry, 58K20
Abstract

The work is a detailed study of rational singularities of multiplicity 3 (RTP-singularities, for short). We give a list of nonisolated hypersurface singularities of which normalisations are the RTP-singularities, and construct their minimal resolution graphs by means of a subdivision of Newton polygons of those -- a method introduced by M. Oka for isolated complete intersection singularities. We show that nonisolated forms of RTP-singularities and their normalisations are both Newton non-degenerate., Comment: 22 pages, 43 figures, v3

Published
2013

7. Examples of finitely determined map-germs of corank 2 from $n$-space to $(n+1)$-space

Author

Altintas, Ayse

Subjects
Mathematics - Algebraic Geometry, 58K40, 32S30
Abstract

We produce new examples supporting the Mond conjecture which can be stated as follows. The number of parameters needed for a miniversal unfolding of a finitely determined map-germ from $n$-space to $(n+1)$-space is less than (or equal to if the map-germ is weighted homogeneous) the rank of the $n$th homology group of the image of a stable perturbation of the map-germ. We give examples of finitely determined map-germs of corank 2 from 3-space to 4-space satisfying the conjecture. We introduce a new type of augmentations to generate series of finitely determined map-germs in dimensions $(n,n+1)$ from a given one in dimensions $(n-1,n)$. We present more examples in dimensions $(4,5)$ and $(5,6)$ based on our examples, and verify the conjecture for them., Comment: v3: final version, to appear in International Journal of Mathematics. -- v2: 14 pages, shortened and revised: section on map-germs from 3-space to 4-space removed, the examples kept; remark 4.11 corrected, now it is remark 4.4; remark 4.12 revised; replaced the term 'reduction' with 'augmentation'

Published
2012

8. Free resolutions for multiple point spaces

Author

Altintas, Ayse and Mond, David

Subjects
Mathematics - Algebraic Geometry, 58K20
Abstract

Let f be a map-germ of corank 1 from complex n-space to complex (n+1)-space, and, for k less than or equal to the multiplicity of f, let $D^k(f)$ be its k'th multiple-point scheme -- the closure of the set of ordered k-tuples of pairwise distinct points sharing the same image. There are natural projections from $D^{k+1}(f)$ to $D^k(f)$, determined by forgetting one member of the (k+1)-tuple. We prove that the matrix of a presentation of $\OO_{D^{k+1}(f)}$ over $\OO_{D^k(f)}$ appears as a certain submatrix of the matrix of a suitable presentation of $\OO_{\CC^n}$ over $\OO_{\CC^{n+1}}$. This does not happen for germs of corank greater than 1., Comment: 15 pages

Published
2011
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9. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable

Author

Sharmin, Sifat, primary, Roos, Izanne, additional, Simpson-Yap, Steve, additional, Malpas, Charles, additional, Sánchez, Marina M, additional, Ozakbas, Serkan, additional, Horakova, Dana, additional, Havrdova, Eva K, additional, Patti, Francesco, additional, Alroughani, Raed, additional, Izquierdo, Guillermo, additional, Eichau, Sara, additional, Boz, Cavit, additional, Zakaria, Magd, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Weinstock-Guttman, Bianca, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Terzi, Murat, additional, Amato, Maria Pia, additional, Karabudak, Rana, additional, Grand’Maison, Francois, additional, Khoury, Samia J, additional, Grammond, Pierre, additional, Lechner-Scott, Jeannette, additional, Buzzard, Katherine, additional, Skibina, Olga, additional, van der Walt, Anneke, additional, Butzkueven, Helmut, additional, Turkoglu, Recai, additional, Altintas, Ayse, additional, Maimone, Davide, additional, Kermode, Allan, additional, Shalaby, Nevin, additional, Pesch, Vincent V, additional, Butler, Ernest, additional, Sidhom, Youssef, additional, Gouider, Riadh, additional, Mrabet, Saloua, additional, Gerlach, Oliver, additional, Soysal, Aysun, additional, Barnett, Michael, additional, Kuhle, Jens, additional, Hughes, Stella, additional, Sa, Maria J, additional, Hodgkinson, Suzanne, additional, Oreja-Guevara, Celia, additional, Ampapa, Radek, additional, Petersen, Thor, additional, Ramo-Tello, Cristina, additional, Spitaleri, Daniele, additional, McCombe, Pamela, additional, Taylor, Bruce, additional, Prevost, Julie, additional, Foschi, Matteo, additional, Slee, Mark, additional, McGuigan, Chris, additional, Laureys, Guy, additional, Hijfte, Liesbeth V, additional, de Gans, Koen, additional, Solaro, Claudio, additional, Oh, Jiwon, additional, Macdonell, Richard, additional, Aguera-Morales, Eduardo, additional, Singhal, Bhim, additional, Gray, Orla, additional, Garber, Justin, additional, Wijmeersch, Bart V, additional, Simu, Mihaela, additional, Castillo-Triviño, Tamara, additional, Sanchez-Menoyo, Jose L, additional, Khurana, Dheeraj, additional, Al-Asmi, Abdullah, additional, Al-Harbi, Talal, additional, Deri, Norma, additional, Fragoso, Yara, additional, Lalive, Patrice H, additional, Sinnige, L G F, additional, Shaw, Cameron, additional, Shuey, Neil, additional, Csepany, Tunde, additional, Sempere, Angel P, additional, Moore, Fraser, additional, Decoo, Danny, additional, Willekens, Barbara, additional, Gobbi, Claudio, additional, Massey, Jennifer, additional, Hardy, Todd, additional, Parratt, John, additional, and Kalincik, Tomas, additional

Published
2023
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12. Real Life Multicenter Comparison of 24-Month Outcomes of Anti-VEGF Therapy in Diabetic Macular Edema in Turkey: Ranibizumab vs. Aflibercept vs. Ranibizumab-Aflibercept Switch

Author

Kucukevcilioglu, Murat, primary, Yeşiltaş, Yağmur Seda, additional, Durukan, Ali Hakan, additional, Unlu, Nurten, additional, Onen, Mehmet, additional, Alp, Mehmet Numan, additional, Kalayci, Defne, additional, Acar, Mehmet Akif, additional, Sekeroglu, Mehmet Ali, additional, Citirik, Mehmet, additional, Altintas, Ayse Gul Kocak, additional, Hazirolan, Dicle, additional, Ozdal, Pinar Cakar, additional, Toklu, Yasin, additional, Bicer, Tolga, additional, Ugurlu, Nagihan, additional, Budakoglu, Ozlem, additional, Yazar, Zeliha, additional, Zeki, Nil Irem Ucgun, additional, Serdar, Kurtulus, additional, Doguizi, Sibel, additional, Erol, Yasemin Ozdamar, additional, Atilgan, Cemile Ucgul, additional, Yorgun, Mucella Arikan, additional, Soba, Dilek Ozcelik, additional, Berker, Nilufer, additional, and Baskan, Ceyda, additional

Published
2023
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14. Comparative effectiveness of autologous hematopoietic stem cell transplant vs Fingolimod, Natalizumab, and Ocrelizumab in highly active relapsing-remitting multiple sclerosis

Author

Kalincik, Tomas, Sharmin, Sifat, Roos, Izanne, Freedman, Mark S., Atkins, Harold, Burman, Joachim, Massey, Jennifer, Sutton, Ian, Withers, Barbara, Macdonell, Richard, Grigg, Andrew, Torkildsen, Øivind, Bo, Lars, Lehmann, Anne Kristine, Havrdova, Eva Kubala, Krasulova, Eva, Trněný, Marek, Kozak, Tomas, van der Walt, Anneke, Butzkueven, Helmut, McCombe, Pamela, Skibina, Olga, Lechner-Scott, Jeannette, Willekens, Barbara, Cartechini, Elisabetta, Ozakbas, Serkan, Alroughani, Raed, Kuhle, Jens, Patti, Francesco, Duquette, Pierre, Lugaresi, Alessandra, Khoury, Samia J., Slee, Mark, Turkoglu, Recai, Hodgkinson, Suzanne, John, Nevin, Maimone, Davide, Sa, Maria Jose, van Pesch, Vincent, Gerlach, Oliver, Laureys, Guy, Van Hijfte, Liesbeth, Karabudak, Rana, Spitaleri, Daniele, Csepany, Tunde, Gouider, Riadh, Castillo-Triviño, Tamara, Taylor, Bruce, Sharrack, Basil, Snowden, John A., Horakova, Dana, Buzzard, Katherine, Terzi, Murat, Prat, Alexandre, Girard, Marc, Grammond, Pierre, Barnett, Michael, Stewart, Grace, Onofrj, Marco, Izquierdo, Guillermo, Eichau, Sara, Grand'Maison, Francois, Prevost, Julie, Van Wijmeersch, Bart, Amato, Maria Pia, Shaygannejad, Vahid, Boz, Cavit, Bolaños, Ricardo Fernandez, Soysal, Aysun, Ramo-Tello, Cristina, Solaro, Claudio, Gobbi, Claudio, Cabrera-Gomez, Jose Antonio, Roullet, Etienne, Zwanikken, Cees, Den braber-Moerland, Leontien, Deri, Norma, Saladino, Maria Laura, Cristiano, Edgardo, Rojas, Juan Ignacio, Vrech, Carlos, Shaw, Cameron, Shuey, Neil, Boggild, Mike, Tan, Ik Lin, Hardy, Todd, Decoo, Danny, Moore, Fraser, Oh, Jiwon, Lalive, Patrice, Ampapa, Radek, Petersen, Thor, Oreja-Guevara, Celia, Perez Sempere, Angel, Dominguez, Jose Andres, Besora, Sarah, Hughes, Stella, Gray, Orla, Grigoriadis, Nikolaos, Piroska, Imre, Rozsa, Csilla, Kasa, Krisztian, Simo, Magdolna, Kovacs, Krisztina, Sas, Attila, Dobos, Eniko, Rajda, Cecilia, McGuigan, Chris, Mason, Deborah, Schepel, Jan, Alkhaboori, Jabir, Rio, Maria Edite, Mihaela, Simu, Al-Harbi, Talal, Altintas, Ayse, Kister, Ilya, Marriott, Mark, Kilpatrick, Trevor, King, John, Nguyen, Ai-Lan, Dwyer, Chris, Monif, Mastura, Taylor, Lisa, Diamanti, Matteo, Chisari, Clara, Toscano, Simona, Salvatore, Lo Fermo, Larochelle, Catherine, De Luca, Giovanna, Di Tommaso, Valeria, Travaglini, Daniela, Pietrolongo, Erika, di Ioia, Maria, Farina, Deborah, Mancinelli, Luca, Hupperts, Raymond, Olascoaga, Javier, Saiz, Albert, Zivadinov, Robert, Benedict, Ralph, Verheul, Freek, Fabis-Pedrini, Marzena, Mrabet, Saloua, Garber, Justin, Sanchez-Menoyo, Jose Luis, Aguera-Morales, Eduardo, Blanco, Yolanda, Al-Asmi, Abdullah, Weinstock-Guttman, Bianca, Fragoso, Yara, de Gans, Koen, and Kermode, Allan

Subjects
Human medicine
Abstract

you are agreeing to our Cookie Policy | Continue JAMA Network HomeJAMA Neurology This Issue Views 2,357 Citations 0 60 Full Text Share Comment Original Investigation May 15, 2023 Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis Tomas Kalincik, MD, PhD1,2; Sifat Sharmin, PhD1,2; Izanne Roos, MBChB, PhD1,2; Mark S. Freedman, MD3; Harold Atkins, MD4; Joachim Burman, MD, PhD5; Jennifer Massey, MBBS, PhD6,7; Ian Sutton, MBBS, PhD6,8; Barbara Withers, MD, PhD7,9; Richard Macdonell, MD, PhD10,11; Andrew Grigg, MD, PhD11,12; Øivind Torkildsen, MD, PhD13; Lars Bo, MD, PhD13; Anne Kristine Lehmann, MD, PhD14; Eva Kubala Havrdova, MD, PhD15; Eva Krasulova, MD, PhD15; Marek Trněný, MD, PhD16; Tomas Kozak, MD, PhD17; Anneke van der Walt, MBBS, PhD18,19; Helmut Butzkueven, MBBS, PhD18,19; Pamela McCombe, MBBS20,21; Olga Skibina, MBBS18,22,23; Jeannette Lechner-Scott, MD, PhD24,25; Barbara Willekens, MD, PhD26,27; Elisabetta Cartechini, MD28; Serkan Ozakbas, MD29; Raed Alroughani, MD30; Jens Kuhle, MD, PhD31; Francesco Patti, MD32,33; Pierre Duquette, MD34; Alessandra Lugaresi, MD, PhD35,36; Samia J. Khoury, MD, PhD37; Mark Slee, MD, PhD38; Recai Turkoglu, MD39; Suzanne Hodgkinson, MD40; Nevin John, MD, PhD41,42; Davide Maimone, MD43; Maria Jose Sa, MD44; Vincent van Pesch, MD, PhD45,46; Oliver Gerlach, MD, PhD47,48; Guy Laureys, MD49; Liesbeth Van Hijfte, MD49; Rana Karabudak, MD50; Daniele Spitaleri, MD51; Tunde Csepany, MD, PhD52; Riadh Gouider, MD53,54; Tamara Castillo-Triviño, MD55; Bruce Taylor, MD, PhD56,57; Basil Sharrack, MD, PhD58; John A. Snowden, MD, PhD59; and the MSBase Study Group Collaborators; and the MSBase Study Group Authors Author Affiliations JAMA Neurol. 2023;80(7):702-713. doi:10.1001/jamaneurol.2023.1184 editorial comment iconEditorial Comment Key Points Question What is the comparative effectiveness of autologous hematopoietic stem cell transplant (AHSCT) vs individual most potent disease-modifying therapies for relapsing-remitting multiple sclerosis (MS), such as natalizumab or ocrelizumab? Findings In this observational comparative effectiveness study of 4915 individuals using a composite cohort from specialized MS centers and the MSBase international registry, the effectiveness of AHSCT was compared with 1 medium-efficacy and 2 high-efficacy disease-modifying therapies (fingolimod, natalizumab, and ocrelizumab) in patients with relapsing-remitting MS, high frequency of relapses, and moderate disability. Over 5 years, AHSCT was associated with substantially lower relapse rate than fingolimod and marginally lower relapse rate than natalizumab and was also associated with a higher rate of recovery from disability compared with fingolimod and natalizumab, but no evidence of difference in clinical outcomes between AHSCT and ocrelizumab was found at 3-year follow-up. Meaning The results indicate that in relapsing-remitting MS, the clinical effectiveness of AHSCT is considerably superior to fingolimod and marginally superior to natalizumab. Abstract Importance Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). Objective To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. Design, Setting, and Participants This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. Exposure AHSCT vs fingolimod, natalizumab, or ocrelizumab. Main outcomes Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. Results Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%). Conclusion In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.

Published
2023

15. A plain language summary on the effectiveness of cladribine tablets compared with other oral treatments for multiple sclerosis: results from the MSBase registry

Author

Spelman, Tim, Ozakbas, Serkan, Alroughani, Raed, Terzi, Murat, Hodgkinson, Suzanne, Laureys, Guy, Kalincik, Tomas, Der Walt, Anneke Van, Yamout, Bassem, Lechner-Scott, Jeannette, Soysal, Aysun, Kuhle, Jens, Sanchez-Menoyo, Jose Luis, Morgado, Yolanda Blanco, Spitaleri, Daniele LA, Pesch, Vincent van, Horakova, Dana, Ampapa, Radek, Patti, Francesco, Macdonell, Richard, Al-Asmi, Abdullah, Gerlach, Oliver, Oh, Jiwon, Altintas, Ayse, Tundia, Namita, Wong, Schiffon L, Butzkueven, Helmut, MSBase Study Group, [missing], and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
teriflunomide (Aubagio®), relapses, cladribine tablets, fingolimod (Gilenya®), Neurology (clinical), lay summary, dimethyl fumarate (Tecfidera®), multiple sclerosis, treatment options
Abstract

What is this summary about? Patient registries contain anonymous data from people who share the same medical condition. The MSBase registry contains information from over 80,000 people living with multiple sclerosis (MS) across 41 countries. Using information from the MSBase registry, the GLIMPSE (Generating Learnings In MultiPle SclErosis) study looked at real-life outcomes in 3475 people living with MS who were treated with cladribine tablets (Mavenclad®) compared with other oral treatments. What were the results? Results showed that people treated with cladribine tablets stayed on treatment for longer than other treatments given by mouth. They also had fewer relapses (also called flare ups of symptoms) than people who received a different oral treatment for their MS. What do the results mean? The results provide evidence that, compared with other oral treatments for MS, cladribine tablets are an effective medicine for people living with MS.

Published
2023

16. Disability accrual in primary and secondary progressive multiple sclerosis

Author

Harding-Forrester, Sam, Roos, Izanne, Nguyen, Ai-Lan, Malpas, Charles B, Diouf, Ibrahima, Moradi, Nahid, Sharmin, Sifat, Izquierdo, Guillermo, Eichau, Sara, Patti, Francesco, Horakova, Dana, Kubala Havrdova, Eva, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grand'Maison, Francois, Onofrj, Marco, Lugaresi, Alessandra, Grammond, Pierre, Ozakbas, Serkan, Amato, Maria Pia, Gerlach, Oliver, Sola, Patrizia, Ferraro, Diana, Buzzard, Katherine, Skibina, Olga, Lechner-Scott, Jeannette, Alroughani, Raed, Boz, Cavit, Van Pesch, Vincent, Cartechini, Elisabetta, Terzi, Murat, Maimone, Davide, Ramo-Tello, Cristina, Yamout, Bassem, Khoury, Samia Joseph, La Spitaleri, Daniele, Sa, Maria Jose, Blanco, Yolanda, Granella, Franco, Slee, Mark, Butler, Ernest, Sidhom, Youssef, Gouider, Riadh, Bergamaschi, Roberto, Karabudak, Rana, Ampapa, Radek, Sánchez-Menoyo, José Luis, Prevost, Julie, Castillo-Trivino, Tamara, McCombe, Pamela A, Macdonell, Richard, Laureys, Guy, Van Hijfte, Liesbeth, Oh, Jiwon, Altintas, Ayse, de Gans, Koen, Turkoglu, Recai, van der Walt, Anneke, Butzkueven, Helmut, Vucic, Steve, Barnett, Michael, Cristiano, Edgardo, Hodgkinson, Suzanne, Iuliano, Gerardo, Kappos, Ludwig, Kuhle, Jens, Shaygannejad, Vahid, Soysal, Aysun, Weinstock-Guttman, Bianca, Van Wijmeersch, Bart, Kalincik, Tomas, MSBase investigators, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Psychiatry and Mental health, Surgery, Neurology (clinical), multiple sclerosis
Abstract

BackgroundSome studies comparing primary and secondary progressive multiple sclerosis (PPMS, SPMS) report similar ages at onset of the progressive phase and similar rates of subsequent disability accrual. Others report later onset and/or faster accrual in SPMS. Comparisons have been complicated by regional cohort effects, phenotypic differences in sex ratio and management and variable diagnostic criteria for SPMS.MethodsWe compared disability accrual in PPMS and operationally diagnosed SPMS in the international, clinic-based MSBase cohort. Inclusion required PPMS or SPMS with onset at age ≥18 years since 1995. We estimated Andersen-Gill hazard ratios for disability accrual on the Expanded Disability Status Scale (EDSS), adjusted for sex, age, baseline disability, EDSS score frequency and drug therapies, with centre and patient as random effects. We also estimated ages at onset of the progressive phase (Kaplan-Meier) and at EDSS milestones (Turnbull). Analyses were replicated with physician-diagnosed SPMS.ResultsIncluded patients comprised 1872 with PPMS (47% men; 50% with activity) and 2575 with SPMS (32% men; 40% with activity). Relative to PPMS, SPMS had older age at onset of the progressive phase (median 46.7 years (95% CI 46.2–47.3) vs 43.9 (43.3–44.4); pConclusionsWe demonstrate later onset of the progressive phase and slower disability accrual in SPMS versus PPMS. This may balance greater baseline disability in SPMS, yielding convergent disability trajectories across phenotypes. The different rates of disability accrual should be considered before amalgamating PPMS and SPMS in clinical trials.

Published
2023

18. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

Author

Rojas, Juan Ignacio, Gray, Orla, Khurana, Dheeraj, Van Wijmeersch, Bart, Grigoriadis, Nikolaos, Inshasi, Jihad, Oh, Jiwon, Aguera-Morales, Eduardo, Fragoso, Yara, Moore, Fraser, Shaw, Cameron, Baghbanian, Seyed Mohammad, Shuey, Neil, Willekens, Barbara, Hardy, Todd A., Decoo, Danny, Sempere, Angel Perez, Field, Deborah, Wynford-Thomas, Ray, Cunniffe, Nick G., Roos, Izanne, Malpas, Charles B., Coles, Alasdair J., Kalincik, Tomas, Brown, J. William L., MSBase Study Grp, MSBase Study Grp, Shaygannejad, Vahid, Daruwalla, Cyrus, ÖZAKBAŞ, SERKAN, Havrdova, Eva Kubala, Horakova, Dana, Alroughani, Raed, BOZ, CAVİT, Patti, Francesco, Onofrj, Marco, Lugaresi, Alessandra, Eichau, Sara, Girard, Marc, Prat, Alexandre, Duquette, Pierre, Yamout, Bassem, Khoury, Samia J., Sajedi, Seyed Aidin, Turkoglu, Recai, Altintas, Ayse, Skibina, Olga, Buzzard, Katherine, Grammond, Pierre, Karabudak, Rana, van der Walt, Anneke, Butzkueven, Helmut, Maimone, Davide, Lechner-Scott, Jeannette, Soysal, Aysun, John, Nevin, Prevost, Julie, Spitaleri, Daniele, Ramo-Tello, Cristina, Gerlach, Oliver, Iuliano, Gerardo, Foschi, Matteo, Ampapa, Radek, van Pesch, Vincent, Barnett, Michael, Shalaby, Nevin, D'hooghe, Marie, Kuhle, Jens, Sa, Maria Jose, Fabis-Pedrini, Marzena, Kermode, Allan, Mrabet, Saloua, Gouider, Riadh, Hodgkinson, Suzanne, Laureys, Guy, Van Hijfte, Liesbeth, Macdonell, Richard, Oreja-Guevara, Celia, Cristiano, Edgardo, McCombe, Pamela, Sanchez-Menoyo, Jose Luis, Singhal, Bhim, Blanco, Yolanda, Hughes, Stella, Garber, Justin, Solaro, Claudio, McGuigan, Chris, Taylor, Bruce, de Gans, Koen, Habek, Mario, Al-Asmi, Abdullah, Mihaela, Simu, Castillo Trivino, Tamara, Al-Harbi, Talal, MSBase Study Group, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, Faculty of Medicine and Pharmacy, Daruwalla, Cyrus [0000-0002-2329-5329], Shaygannejad, Vahid [0000-0001-5511-509X], Horakova, Dana [0000-0003-1915-0036], Alroughani, Raed [0000-0001-5436-5804], Patti, Francesco [0000-0002-6923-0846], Lugaresi, Alessandra [0000-0003-2902-5589], Eichau, Sara [0000-0001-9159-3128], Duquette, Pierre [0000-0001-7231-1754], Sajedi, Seyed Aidin [0000-0002-6704-9787], van der Walt, Anneke [0000-0002-4278-7003], Lechner-Scott, Jeannette [0000-0002-3850-447X], Barnett, Michael [0000-0002-2156-8864], Oreja-Guevara, Celia [0000-0002-9221-5716], Habek, Mario [0000-0002-3360-1748], Castillo Triviño, Tamara [0000-0002-9249-3185], Inshasi, Jihad [0000-0001-5892-751X], Oh, Jiwon [0000-0001-5519-6088], Fragoso, Yara [0000-0001-8726-089X], Baghbanian, Seyed Mohammad [0000-0002-8138-7504], Hardy, Todd A [0000-0003-4145-3172], Decoo, Danny [0000-0001-7689-3114], Roos, Izanne [0000-0003-0371-3666], Kalincik, Tomas [0000-0003-3778-1376], Brown, J William L [0000-0002-7737-5834], Apollo - University of Cambridge Repository, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Neuroscience(all), Multiple sclerosis, prognosis, multiple sclerosis, Prognosis, Multiple Sclerosis, Relapsing-Remitting, Neurology, Recurrence, Medicine and Health Sciences, Humans, Human medicine, Neurology (clinical)
Abstract

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS. Methods: We redefined mild relapses in MSBase as ‘non-disabling’, and moderate or severe relapses as ‘disabling’. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. Results: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00–1.68) or given platform DMTs ( n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15–1.54), but not if given high-efficacy DMTs ( n = 572 vs 3534; HR = 0.90, 95% CI = 0.71–1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. Conclusion: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

Published
2023

19. Effects of the epiretinal membrane on the outcomes of intravitreal dexamethasone implantation for macular edema secondary to branch retinal vein occlusion

Author

Altintas, Ayse Gul Kocak and Ilhan, Cagri

Subjects
Intravitreal injections, Macular edema/ etiology, genetic structures, Tomography, optical coherence, Drug implants, Dexametasona, Injeções intravítreas, Edema macular/etiologia, Oclusão da veia retiniana/complicações, eye diseases, Dexamethasone, Epiretinal membrane, Tomografia de coerência óptica, Membrana epirretiniana, Retinal vein occlusion/complications, Implantes de medicamento
Abstract

Purpose: To investigate the effects of epiretinal membrane formation on the clinical outcomes of intravitreal dexamethasone implantation for macular edema secondary to branch retinal vein occlusion. Methods: This retrospective interventional case series includes the treatment of naive patients with macular edema secondary to non-ischemic branch retinal vein occlusion who underwent intravitreal dexamethasone implantation. The patients were divided into two groups as follows: Group 1 (n=25), comprised of patients with macular edema secondary to branch retinal vein occlusion without epiretinal membrane, and Group 2 (n=16), comprised of patients with macular edema secondary to branch retinal vein occlusion with an epiretinal membrane. Corrected visual acuity, central macular thickness, and central macular volume values were measured before and after treatment. The clinical outcomes of the groups were compared. Results: Mean age and male-to-female ratio were similar between the two groups (p>0.05, for both). The baseline and final corrected visual acuity values, central macular thickness, and central macular volumes of the groups were similar (p>0.05, for all). All the parameters were significantly improved after intravitreal dexamethasone implantation treatment (p0.05, for both). The mean number of intravitreal dexamethasone implantations was 2.1 ± 1.0 (range, 1-4) in Group 1 and 3.0 ± 1.2 (range, 1-5) in Group 2 (p=0.043). Conclusion: Epiretinal membrane formation had no effects on the baseline and final clinical parameters, including corrected visual acuity and central macular thickness and volume. The only parameter affected by the presence of epiretinal membrane formation is the number of intravitreal dexamethasone implantations, a greater number of which is needed for macular edema secondary to branch retinal vein occlusion with an epiretinal membrane. RESUMO Objetivo: Investigar os efeitos da formação de uma membrana epirretiniana nos resultados clínicos da implantação intravítrea de dexametasona para edema macular secundário à oclusão de um ramo da veia retiniana. Métodos: Esta série retrospectiva de casos intervencionais inclui o tratamento de indivíduos com edema macular secundário à oclusão não isquêmica de um ramo da veia retiniana, sem tratamento prévio e que foram submetidos a implantação intravítrea de dexametasona. Os indivíduos foram divididos em dois grupos: Grupo 1 (n=25), composto por indivíduos com edema macular secundário à oclusão de um ramo da veia retiniana sem a presença de uma membrana epirretiniana, e Grupo 2 (n=16), composto por indivíduos com edema macular secundário à oclusão de um ramo da veia retiniana com a presença de uma membrana epirretiniana. Os valores da acuidade visual corrigida, espessura macular central e volume macular central foram obtidos antes e após o tratamento. Os resultados clínicos dos grupos foram comparados. Resultados: A média de idade e a proporção entre homens e mulheres foram semelhantes nos dois grupos (p>0,05 para ambos os valores). Os valores iniciais e finais da acuidade visual corrigida, espessura macular central e volume macular central foram semelhantes nos dois grupos (p>0,05 para todos os valores). Todos os parâmetros melhoraram significativamente após o tratamento com implante de dexametasona intravítrea (p0,05 para ambos os valores). O número médio de implantações intravítreas de dexametasona foi 2,1 ± 1,0 (faixa de 1-4) no Grupo 1 e 3,0 ± 1,2 (faixa de 1-5) no Grupo 2 (p=0,043). Conclusão: A formação de uma membrana epirretiniana não tem efeitos sobre os parâmetros clínicos iniciais e finais, incluindo a acuidade visual corrigida, a espessura macular central e o volume macular central. O único parâmetro afetado pela formação de uma membrana epirretiniana é o número de implantações intravítreas de dexametasona, sendo necessário um número maior de implantações em casos de edema macular secundário à oclusão de um ramo da veia retiniana com a presença de uma membrana epirretiniana.

Published
2022

21. Retinal Optical Coherence Tomography in Neuromyelitis Optica

Author

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

Published
2021
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22. A 52-Year-Old Man With Progressive Weakness and Incontinence

Author

Altintas, Ayse, primary, Danyeli, Ayca Ersen, additional, Bozkurt, Subutay Berke, additional, Uysal, Sanem Pinar, additional, Akpek, Sergin, additional, Aygun, Murat Serhat, additional, Akay, Olga Meltem, additional, Kahyaoglu, Bulent, additional, Peker, Selcuk, additional, Ure, Umit Barbaros, additional, and Ferhanoglu, Burhan, additional

Published
2021
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23. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

Author

Bakker, Mark K., van der Spek, Rick A.A., van Rheenen, Wouter, Morel, Sandrine, Bourcier, Romain, Hostettler, Isabel C., Alg, Varinder S., van Eijk, Kristel R., Koido, Masaru, Akiyama, Masato, Terao, Chikashi, Matsuda, Koichi, Walters, Robin G., Lin, Kuang, Li, Liming, Millwood, Iona Y., Chen, Zhengming, Rouleau, Guy A., Zhou, Sirui, Rannikmäe, Kristiina, Sudlow, Cathie L.M., Houlden, Henry, van den Berg, Leonard H., Dina, Christian, Naggara, Olivier, Gentric, Jean-Christophe, Shotar, Eimad, Eugène, François, Desal, Hubert, Winsvold, Bendik S., Børte, Sigrid, Johnsen, Marianne Bakke, Brumpton, Ben M., Sandvei, Marie Søfteland, Willer, Cristen J., Hveem, Kristian, Zwart, John-Anker, Verschuren, W. M. Monique, Friedrich, Christoph M., Hirsch, Sven, Schilling, Sabine, Dauvillier, Jérôme, Martin, Olivier, Martinsen, Amy E, Aamodt, Anne Hege, Skogholt, Anne Heidi, Sandset, Else Charlotte, Kristoffersen, Espen S, Ellekjaer, Hanne, Heuch, Ingrid, Nielsen, Jonas Bille, Hagen, Knut, Fritsche, Lars, Thomas, Laurent F., Pedersen, Linda, Gabrielsen, Maiken E, Vigeland, Maria Dehli, Holmen, Oddgeir, Zhou, Wei, Chen, Junshi, Chen (PI), Zhengming, Clarke, Robert, Collins, Rory, Guo, Yu, Li (PI), Liming, Liu, Depei, Lv, Jun, Peto, Richard, Walters, Robin, Avery, Daniel, Boxall, Ruth, Bennett, Derrick, Chang, Yumei, Chen, Yiping, Du, Huaidong, Gan, Wei, Gilbert, Simon, Hacker, Alex, Hill, Michael, Holmes, Michael, Iona, Andri, Kartsonaki, Christiana, Kerosi, Rene, Kong, Ling, Lancaster, Garry, Lewington, Sarah, McDonnell, John, Millwood, Iona, Nie, Qunhua, Ryder, Paul, Sansome, Sam, Schmidt-Valle, Dan, Sherliker, Paul, Sohoni, Rajani, Stevens, Becky, Turnbull, Iain, Wang, Lin, Wright, Neil, Yang, Ling, Yang, Xiaoming, Yao, Pang, Bian, Zheng, Han, Xiao, Hou, Can, Pei, Pei, Liu, Chao, Yu, Canqing, Pang, Zengchang, Gao, Ruqin, Li, Shanpeng, Wang, Shaojie, Liu, Yongmei, Du, Ranran, Cheng, Liang, Tian, Xiaocao, Zhang, Hua, Zhai, Yaoming, Ning, Feng, Sun, Xiaohui, Li, Feifei, Lv, Silu, Wang, Junzheng, Hou, Wei, Zou, Mingyuan, Yan, Shichun, Zhou, Xue, Yu, Bo, Li, Yanjie, Xu, Qinai, Kang, Quan, Guo, Ziyan, Wang, Dan, Hu, Ximin, Chen, Jinyan, Fu, Yan, Wang, Xiaohuan, Weng, Min, Guo, Zhendong, Wu, Shukuan, Li, Yilei, Li, Huimei, Wu, Ming, Zhou, Yonglin, Zhou, Jinyi, Tao, Ran, Yang, Jie, Su, Jian, liu, Fang, Zhang, Jun, Hu, Yihe, Lu, Yan, Ma, Liangcai, Tang, Aiyu, Hua, Yujie, Jin, Jianrong, Liu, Jingchao, Tang, Zhenzhu, Chen, Naying, Huang, Ying, Li, Mingqiang, Meng, Jinhuai, Pan, Rong, Jiang, Qilian, Lan, Jian, Liu, Yun, Wei, Liuping, Zhou, Liyuan, Chen, Ningyu, Wang, Ping, Meng, Fanwen, Qin Sisi Wang, Yulu, Wu, Xianping, Zhang, Ningmei, Chen, Xiaofang, Zhou, Weiwei, Luo, Guojin, Li, Jianguo, Zhong, Xunfu, Liu, Jiaqiu, Sun, Qiang, Ge, Pengfei, Ren, Xiaolan, Dong, Caixia, Zhang, Hui, Mao, Enke, Wang, Xiaoping, Wang, Tao, Zhang, Xi, Zhou, Ding Zhang, Zhou, Gang, Feng, Shixian, Chang, Ling, Fan, Lei, Gao, Yulian, He, Tianyou, Sun, Huarong, He, Pan, Hu, Chen, Zhang, Xukui, Wu, Huifang, Yu, Min, Hu, Ruying, Wang, Hao, Gong, Weiwei, Wang, Meng, Xie, Kaixu, Chen, Lingli, Pan, Dongxia, Gu, Qijun, Huang, Yuelong, Chen, Biyun, Yin, Li, Liu, Huilin, Fu, Zhongxi, Xu, Qiaohua, Xu, Xin, Zhang, Hao, Long, Huajun, Zhang, Libo, Nagai, Akiko, Muto, Kaori, Hirata, Makoto, Morisaki, Takayuki, Yamashita, Yasushi, Kamatani, Yoichiro, Kambara, Yoko, Murakami, Yoshinori, Masumoto, Akihide, Nagayama, Satoshi, Miki, Yoshio, Yoshimori, Kozo, Fujioka, Tomoaki, Takata, Ryo, Yamaji, Ken, Takahashi, Kazuhisa, Asai, Satoshi, Takahashi, Yasuo, Minami, Shiro, Yamaguchi, Hiroki, Koretsune, Yukihiro, Nishizawa, Yasuko, Kodama, Ken, Kutsumi, Hiromu, Suzuki, Takao, Sinozaki, Nobuaki, Murayama, Shigeo, Furukawa, Yoichi, Yamanashi, Yuji, Papagiannaki, Chrisanthi, Piotin, Michel, Trystram, Denis, Edjlali-Goujon, Myriam, Boulouis, Grégoire, Rodriguez, Christine, Hassen, Waghi Ben, Saleme, Suzanna, Mounayer, Charbel, Rouchaud, Aymeric, Levrier, Olivier, Aguettaz, Pierre, Combaz, Xavier, Pasco, Anne, l’Allinec, Vincent, Bintner, Marc, Molho, Marc, Pascale, Gauthier, Chivot, Cyril, Costalat, Vincent, Darganzil, Cyril, Bonafé, Alain, Januel, Anne Christine, Michelozzi, Caterina, Cognard, Christophe, Bonneville, Fabrice, Tall, Philippe, Darcourt, Jean, Biondi, Alessandra, Iosif, Cristina, Ferre, Jean Christophe, Gauvrit, Jean Yves, Eugene, François, Raoult, Hélène, Gentric, Jean Christophe, Ognard, Julien, Anxionnat, René, Gory, Benjamin, Bracard, Serge, Derelle, Anne Laure, Tonnelet, Romain, Spelle, Laurent, Ikka, Léon, Ozanne, Augustin, Gallas, Sophie, Caroff, Jildaz, Achour, Nidal Ben, Moret, Jacques, Chabert, Emmanuel, Berge, Jérôme, Marnat, Gaultier, Barreau, Xavier, Gariel, Florent, Clarencon, Frédéric, Aggour, Mohammed, Ricolfi, Frédéric, Chavent, Adrien, Thouant, Pierre, Lebidinsky, Pablo, Lemogne, Brivael, Herbreteau, Denis, Bibi, Richard, Janot, Kevin, Pierot, Laurent, Soize, Sébastien, Labeyrie, Marc Antoine, Vandendries, Christophe, Kazemi, Appoline, Leclerc, Xavier, Pruvo, Jean Pierre, Bricout, Nicolas, Velasco, Stéphane, Boucebci, Samy, Lemmens, Robin, Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean-Louis, Deltour, Sandrine, Leder, Sara, Léger, Anne, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Jacquin, Agnès, Moulin, Thierry, Vuillier, Fabrice, Tzourio, Christophe, Santos, Michael Dos, Malik, Rainer, Hausser, Ingrid, Thomas-Feles, Constanze, Weber, Ralf, Grond-Ginsbach, Caspar, Hacke, Werner, Giossi, Alessia, Volonghi, Irene, Costa, Paolo, del Zotto, Elisabetta, Morotti, Andrea, Poli, Loris, Muiesan, Maria Lorenza, Salvetti, Massimo, Rosei, Enrico Agabiti, Lanfranconi, Silvia, Baron, Pierluigi, Ferrarese, Carlo, Susani, Emanuela, Giacalone, Giacomo, Paolucci, Stefano, Palmirotta, Raffaele, Guadagni, Fiorella, Paciaroni, Maurizio, Ballabio, Elena, Parati, Eugenio A., Fluri, Felix, Hatz, Florian, Gisler, Dominique, Amort, Margareth, Bevan, Steve, James, Tom, Olsson, Sandra, Holmegaard, Lukas, Altintas, Ayse, Martin, Juan José, Kittner, Steven, Mitchell, Braxton, Stine, Colin, O’Connell, Jeff, Dueker, Nicole, Koudstaal, Peter J., de Lau, Lonneke M.L., Hofman, Albert, Verhaaren, Benjamin F, Uitterlinden, Andre G, Montaner, Joan, Mendioroz, Maite, Yadav, Sunaina, Khan, Muhammad Saleem, Wilder, Michael, van Dijk, Ewoud, Maaijwee, Noortje, Rutten-Jacobs, Loes, Kramer, Jamie, Malik, Shaneela, Brott, Thomas G, Brown, Robert D, Singleton, Andrew, Hardy, John, Rich, Stephen S, Tanislav, Christian, Jungehülsing, Jan, Werring, David, Alg, Varinder, Hostettler, Isabel, Bonner, Stephen, Walsh, Daniel, Bulters, Diederik, Kitchen, Neil, Brown, Martin, Grieve, Joan, Roberts, Gareth, Jones, Timothy, Critchley, Giles, Sharma, Pankaj, Nelson, Richard, Whitfield, Peter, Ross, Stuart, Patel, Hiren, Eldridge, Paul, Saastamoinen, Kari, Patel, Umang, Lawrance, Enas, Vandabona, Subha, Mendelow, David, Teal, Rachel, Warner, Orlando, Kirkpatrick, Peter, Seshadri, Sudha, Kilarski, Laura, Hyacinth, Hyacinth I, Oliveira, Jamary, Marini, Sandro, Nyquist, Paul, Lewis, Cathryn, Norrving, Bo, Smith, Gustav, Rosand, Jonathan, Biffi, Alessandro, Kourkoulis, Christina, Anderson, Chris, Giese, Anne-Katrin, Bang, Oh Young, Chung, Jong-Won, Kim, Gyeong-Moon, Zhuang, Qishuai, Sheu, Wayne, Smalley, June, Howson, Joanna, Granata, Alessandra, Markus, Hugh, Wardlaw, Joanna, Cole, John, Thalamuthu, Anbupalam, Hopewell, Jemma, Worrall, Bradford, Bis, Josh, Tirschwell, David, Reiner, Alex, Dhar, Raj, Lee, Jin-Moo, Mortenson, Janne, Wassertheil-Smoller, Sylvia, Prasad, Kameshwar, Fisher, Mark, Traenka, Christopher, Wang, Xingwu, Wang, Yongjun, Rouanet, Francois, Sibon, Igor, Sarnowski, Chloé, Maillard, Pauline, Aparicio, Hugo Javier, Dupuis, Josee, Yang, Qiong, Luvizutto, Gustavo, Chasman, Daniel, Rexrode, Kathryn, Harriot, Andrea, Phuah, Chia-Ling, Santo, Gustavo, Gerard, Jen, Liu, Guiyou, Aaron, Sanjith, Christudass, Christhunesa S., Salomi, BSB, Sanghera, Dharambir, Boehme, Amelia, Elkind, Mitchell, Gretarsdottir, Solveig, Lange, Leslie, Rost, Natalia, James, Michael, Stewart, Jill, Goldstein, Larry, Waddy, Salina, Vojinovic, Dina, Ikram, Arfan, Thijs, Vincent, Parati, Eugenio, Boncoraglio, Giorgio, Kooperberg, Charles, Abboud, Sherrine, Zand, Ramin, Bijlenga, Philippe, Selim, Magdy, Happola, Olli, Strbian, Daniel, Tomppo, Liisa, Pathak, Abhishek, Pfeiffer, Dorothea, Aires, de Buenos, de Carvalho, Joao Jose Freitas, Ribeiro, Priscila, Torres, Nuria, Barboza, Miguel, Plomaritoglou, Androniki, Bjorkegren, Johan, Chan, Yu-Feng Yvonne, Gudnason, Villi, Jimenez-Conde, Jordi, Soriano, Carolina, Roquer, Jaume, Bentley, Paul, Tournier-Lasserve, Elisabeth, Dufouil, Carole, Debette, Stephanie, Mishra, Aniket, Wee, Lawrence, Siddiqi, Saima, Wu, Jer-Yuarn, Ko, Tai-Ming, Bione, Silvia, Jood, Katarina, Tatlisumak, Turgut, Arauz, Antonio, Korostynski, Michal, Launer, Lenore, Yue, Suo, bersano, anna, Juchniewicz, Karol Józef, Mateusz, Adamski, Pera, Joanna, Wnuk, Marcin, Levi, Christopher, Gusdon, Aaron, Kostulas, Konstantinos, Maxwell, Jessye, Duering, Marco, Jagiella, Jeremiasz, Hata, Jun, Ninomiya, Toshiharu, Nguyen, Vinh, Thorarinsson, Bjorn Logi, Lee, Tsong-Hai, Rakitko, Alexandr, Dichgans, Martin, Lindgren, Arne, Wasselius, Johan, Drake, Mattias, Stenman, Martin, Ilinca, Andreea, Staals, Julie, Sadr-Nabavi, Ariane, Crawford, Katherine, Lena, Umme, Mateen, Farrah, Ay, Hakan, Wu, Ona, Schirmer, Markus, Romero, Javier, Cramer, Steve, Golland, Polina, Mueller, Bertram, Brown, Robert, Meschia, James, Ross, Owen A., Pare, Guillaume, Chong, Mike, mansour, Ossama yassin, Karaszewski, Bartosz, Enzinger, Christian, Schmidt, Reinhold, Seiler, Stephan, Pichler, Alexander, Ovbiagele, Bruce, Yamada, Yoshiji, Rundek, Tatjana, Blanton, Susan, P, John, Chern, Joseph, O'Donnell, Chris, Corriveau, Roderick, Bhattacharya, Pallab, Gwinn, Katrina, CHANDRA, BHARATENDU, Chen, Christopher, Kalaria, Raj, Koenig, Jim, Singh, Om Prakash, Olugbodi, Akintomi, Giralt, Eva, Saleheen, Danish, de Leeuw, Frank-Erik, Klijn, Karin, Olesen, Jes, Kubo, Michiaki, Spence, David, Pedersen, Annie, Olsson, Maja, Martín, Juan José, Braga, Gabriel, Xu, Huichun, Assimes, Tim, Raskurazhev, Anton, Lee, Wei Ling, Burri, Philippe, Frid, Petrea, GmbH, Heilbronn, Deng, Zhen, Habibi-koolaee, Mahdi, Vijayan, Murali, Leung, Thomas, Wong, Lawrence, Mok, Vincent, Choy, Richard, Jern, Christina, Lebedeva, Elena, Farrall, Martin, Jiayuan, Xu, Loo, Keat Wei, Rinkel, Gabriel, Magnus, Rudolf, Goncalves, Anderson, Franca, Paulo, Cendes, Iscia, Carrera, Caty, Fernandez-Cadenas, Israel, Kim, Helen, Rolfs, Arndt, Owolabi, Mayowa, Bakker, Mark, Ruigrok, Ynte, Hauer, Allard, Pulit, Sara L., Algra, Ale, van der Laan, Sander W., Macleod, Mary, Howard, George, Tiwari, Hemant, Irvin, Ryan, Albright, Karen C., Perry, Rodney, Kidwell, Chelsea, Pavlovic, Aleksandra, Sargurupremraj, Murali, Schilling, Sabrina, Pezzini, Alessandro, Abd-Allah, Foad, DeCarli, Charles, Liebeskind, David, Traylor, Matthew, Tan, Rhea, Danesh, John, Larsson, Susanna C., Rutten, Loes, Donatti, Amanda, Avelar, Wagner, Broderick, Joseph, Woo, Daniel, Kissela, Brett, Ibenez, Laura Garcia, Salman, Rustam, Sudlow, Cathie, McDonough, Caitrin Wheeler, Silliman, Scott, Magvanjav, Oyunbileg, van Agtmael, Tom, Walters, Matthew, Lorentzen, Erik, Stanne, Tara, Olsson, Martina, Nakagawa, Kazuma, Akinyemi, Rufus, Cotlatciuc, Ioana, O'Connell, Jeff, Sparks, Mary, Sorkin, John, Dave, Tushar, Naylor, Jill, Brown, Devin, Du, Rose, Kulik, Tobias B., Attia, John, Faber, James E, Rothwell, Peter, Márquez, Elsa Valdés, Mancuso, Michelangelo, Souza, Doralina Brum, de Silva, Ranil, Vibo, Riina, Korv, Janika, Maguire, Jane, Fornage, Myriam, Illoh, Kachikwu, Milewicz, Dianna, Majersik, Jennifer, DeHavenon, Adam, Kalani, Yashar, Alexander, Matthew, Cushman, Mary, Sale, Michele, Owens, Debra, Keene, Keith, Rich, Stephe, Psaty, Bruce, Longstreth, Will, Atadzhanov, Masharip, Wolfe, Stacey Quintero, Langefeld, Carl, Bushnell, Cheryl, Cruchaga, Carlos, Konrad, Jan, Liu, Junfeng, Sheth, Kevin, Falcone, Guido, Donahue J, Kathleen, Jones, Gregory T., Bown, Matthew J., Ko, Nerissa U., Coleman, Jonathan R.I., Breen, Gerome, Zaroff, Jonathan G., Klijn, Catharina J.M., Sargurupremraj, Muralidharan, Amouyel, Philippe, Debette, Stéphanie, Rinkel, Gabriel J.E., Worrall, Bradford B., Slowik, Agnieszka, Gaál-Paavola, Emilia I., Niemelä, Mika, Jääskeläinen, Juha E., von Und Zu Fraunberg, Mikael, Lindgren, Antti, Broderick, Joseph P., Werring, David J., Redon, Richard, Veldink, Jan H., Ruigrok, Ynte M., Stroke, HUNT All-In, Group, China Kadoorie Biobank Collaborative, Consortium, BioBank Japan Project, Group, ICAN Study, Group, CADISP, investigators, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, (ISGC), International Stroke Genetics Consortium, Morel, Sandrine, and Bijlenga, Philippe Alexandre Pierre

Subjects
genetics [Blood Pressure], Medizin, Genome-wide association study, Blood Pressure, Disease, ddc:616.07, Bioinformatics, 616: Innere Medizin und Krankheiten, 0302 clinical medicine, Risk Factors, physiopathology [Hypertension], genetics [Genetic Predisposition to Disease], Genetic risk factor, Stroke, 0303 health sciences, Smoking, genetics [Smoking], genetics [Intracranial Aneurysm], Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Cerebrovascular disorder, 3. Good health, genetics [European Continental Ancestry Group], Hypertension, genetics [Polymorphism, Single Nucleotide], Subarachnoid hemorrhage, pathology [Intracranial Aneurysm], genetics [White People], Biology, Genetic correlation, pathology [Endothelial Cells], Polymorphism, Single Nucleotide, Article, White People, 03 medical and health sciences, Aneurysm, Asian People, ddc:570, Genetics, medicine, Humans, Genetic Predisposition to Disease, cardiovascular diseases, 030304 developmental biology, genetics [Subarachnoid Hemorrhage], genetics [Asian Continental Ancestry Group], 572: Biochemie, genetics [Asian People], pathology [Subarachnoid Hemorrhage], adverse effects [Smoking], Endothelial Cells, Subarachnoid Hemorrhage, medicine.disease, Intracranial aneurysm, Genetic architecture, ddc:616.8, Case-Control Studies, genetics [Hypertension], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

An author correction to this article published in December 2020 is available at https://doi.org/10.1038/s41588-020-00760-4. Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

Published
2021

24. 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

25. 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

26. 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

27. 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

28. 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

Barnett, Michael, primary, Bergsland, Niels, additional, Weinstock-Guttman, Bianca, additional, Butzkueven, Helmut, additional, Kalincik, Tomas, additional, Desmond, Patricia, additional, Gaillard, Frank, additional, van Pesch, Vincent, additional, Ozakbas, Serkan, additional, Rojas, Juan Ignacio, additional, Boz, Cavit, additional, Altintas, Ayse, additional, Wang, Chenyu, additional, Dwyer, Michael G., additional, Yang, Suzie, additional, Jakimovski, Dejan, additional, Kyle, Kain, additional, Ramasamy, Deepa P., additional, and Zivadinov, Robert, additional

Published
2021
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29. The MSBase pregnancy, neonatal outcomes, and women’s health registry

Author

Jokubaitis, Vilija G., primary, Skibina, Olga, additional, Alroughani, Raed, additional, Altintas, Ayse, additional, Butzkueven, Helmut, additional, Eichau, Sara, additional, Fragoso, Yara, additional, Hellwig, Kerstin, additional, Hughes, Stella E., additional, Rath, Louise, additional, van der Walt, Anneke, additional, and Gray, Orla, additional

Published
2021
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30. Early clinical markers of aggressive multiple sclerosis

Author

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

Published
2020
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32. Sex effects across the lifespan in women with multiple sclerosis

Author

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

Published
2020
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34. 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

36. A 52-Year-Old Man With Progressive Weakness and Incontinence

Author

Altintas, Ayse, Danyeli, Ayca Ersen, Bozkurt, Subutay Berke, Uysal, Sanem Pinar, Akpek, Sergin, Aygun, Murat Serhat, Akay, Olga Meltem, Kahyaoglu, Bulent, Peker, Selcuk, Ure, Umit Barbaros, and Ferhanoglu, Burhan

Abstract

Here we report a challenging case of a 52-year-old man presenting with subacute constipation, urinary retention, impotence, absent Achilles reflexes, and hypoesthesia in S2-S5 dermatomes. We review the clinical decision-making as the symptoms evolved and diagnostic testing changed over time. Once the diagnosis is settled, we discuss the sign and symptoms, additional diagnostic tools, treatment options and prognosis.

Published
2022
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39. 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

41. Pregnancy and the Use of Disease-Modifying Therapies in Patients with Multiple Sclerosis: Benefits versus Risks

Author

Alroughani, Raed, Altintas, Ayse, Al Jumah, Mohammed, Sahraian, Mohammadali, Alsharoqi, Issa, AlTahan, Abdurahman, Daif, Abdulkader, Dahdaleh, Maurice, Deleu, Dirk, Fernandez, Oscar, Grigoriadis, Nikolaos, Inshasi, Jihad, Karabudak, Rana, Taha, Karim, Totolyan, Natalia, Yamout, Bassem I., Zakaria, Magd, and Bohlega, Saeed

Subjects
Article Subject
Abstract

The burden of multiple sclerosis (MS) in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs), which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-β appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation.

Published
2016
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42. Prognostic significance of pulsatile tinnitus in cervical artery dissection

Author

Kellert, L., Kloss, M., Pezzini, Alessandro, Debette, S., Leys, D., Caso, V., Thijs, V. N., Bersano, A., Touzé, E., Tatlisumak, T., Traenka, C., Lyrer, P. A., Engelter, S. T., Metso, T. M., Grond Ginsbach, C., Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean Louis, Deltour, Sandrine, Léger, Anne, Canaple, Sandrine, Godefroy, Olivier, Béjot, Yannick, Moulin, Thierry, Vuillier, Fabrice, Dos Santos, Michael, Malik, Rainer, Hausser, Ingrid, Brandt, Tobias, Thomas Feles, Constanze, Weber, Ralf, Costa, Paolo, Poli, Loris, Morotti, Andrea, Padovani, Alessandro, Lanfranconi, Silvia, Baron, Pierluigi, Ferrarese, Carlo, Giacolone, Giacomo, Paolucci, Stefano, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Amort, Margareth, Bevan, Steve, Altintas, Ayse, Heidelberg University Hospital [Heidelberg], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Università degli Studi di Perugia = University of Perugia (UNIPG), University Hospitals Leuven [Leuven], Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study group, Kellert, L, Kloss, M, Pezzini, A, Debette, S, Leys, D, Caso, V, Thijs, V, Bersano, A, Touzé, E, Tatlisumak, T, Traenka, C, Lyrer, P, Engelter, S, Metso, T, Grond Ginsbach, C, Pandolfo, M, Bodenant, M, Louillet, F, Mas, J, Deltour, S, Léger, A, Canaple, S, Godefroy, O, Béjot, Y, Moulin, T, Vuillier, F, Dos Santos, M, Malik, R, Hausser, I, Brandt, T, Thomas Feles, C, Weber, R, Costa, P, Poli, L, Morotti, A, Padovani, A, Lanfranconi, S, Baron, P, Ferrarese, C, Giacolone, G, Paolucci, S, Fluri, F, Hatz, F, Gisler, D, Amort, M, Bevan, S, and Altintas, A

Subjects
Adult, Male, medicine.medical_specialty, Cervical Artery, Vertebral artery dissection, acute ischaemic stroke, cervical artery dissection, outcome, pulsatile tinnitus, Neurology (clinical), Neurology, Dissection (medical), 030204 cardiovascular system & hematology, Brain Ischemia, Tinnitus, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Modified Rankin Scale, medicine.artery, Internal medicine, medicine, Humans, Stroke, Vertebral Artery Dissection, business.industry, Odds ratio, Middle Aged, Prognosis, medicine.disease, Confidence interval, Surgery, Cardiology, Female, Internal carotid artery, business, pulsatile tinnitu, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background and purpose Our aim was to investigate whether pulsatile tinnitus (PT) in cervical artery dissection (CeAD) has prognostic significance. Methods All CeAD patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study with documentation of PT were analysed. The presence of PT was systematically assessed using a standardized questionnaire. Stroke severity at admission was defined according to the National Institutes of Health Stroke Scale (NIHSS). Excellent outcome after 3 months was defined as a modified Rankin Scale of 0–1. Results Sixty-three of 778 patients (8.1%) reported PT. PT+ patients presented less often with ischaemic stroke (41.3% vs. 63.9%, P < 0.001), more often with dissection in the internal carotid artery (85.7% vs. 64.2%, P = 0.001), less often with vessel occlusion (19.0% vs. 34.1%, P = 0.017) and more often with excellent outcome at 3 months (92.1% vs. 75.4%, P = 0.002). Logistic regression analysis identified PT as an independent predictor of excellent outcome after 3 months [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.22–12.87] adjusted to significant outcome predictors NIHSS on admission (OR 0.82, 95% CI 0.79–0.86), Horner syndrome (OR 1.95, 95% CI 1.16–3.29) and vessel occlusion (OR 0.62, 95% CI 0.40–0.94) and to non-significant predictors age, sex, pain and location of CeAD. Conclusion The presence of PT in CeAD is associated with a benign clinical course and predicts a favourable outcome.

Published
2016

43. Next generation sequencing analysis of patients with familial cervical artery dissection

Author

Grond-Ginsbach, Caspar, primary, Brandt, Tobias, additional, Kloss, Manja, additional, Aksay, Suna Su, additional, Lyrer, Philipp, additional, Traenka, Christopher, additional, Erhart, Philipp, additional, Martin, Juan Jose, additional, Altintas, Ayse, additional, Siva, Aksel, additional, de Freitas, Gabriel R, additional, Thie, Andreas, additional, Machetanz, Jochen, additional, Baumgartner, Ralf W, additional, Dichgans, Martin, additional, and Engelter, Stefan T, additional

Published
2017
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46. Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Author

Debette, Stéphanie, Kamatani, Yoichiro, Wolf, Christiane, Agabiti Rosei, Enrico, Lanfranconi, Silvia, Ferrarese, Carlo, Susani, Emanuela, Bicocca, Milano, Giacalone, Giacomo, Paolucci, Stefano, Palmirotta, Raffaele, Paciaroni, Maurizio, Ballabio, Elena, Dittrich, Ralf, Parati, Eugenio A, Ciusani, Emilio, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Amort, Margareth, Bevan, Steve, James, Tom, Olsson, Sandra, Holmegaard, Lukas, Touzé, Emmanuel, Altintas, Ayse, Martin, Juan José, Kittner, Steven, MItchell, Braxton, Stine, Colin, O'Connell, Jeff, Dueker, Nicole, Koudstaal, Peter J, de Lau, Lonneke M L, Hofman, Albert, Southerland, Andrew M, Verhaaren, Benjamin F, Uitterlinden, Andre G, Montaner, Joan, Mendioroz, Maite, Yadav, Sunaina, Khan, Muhammad Saleem, Wilder, Michael, van Dijk, Ewoud, Maaijwee, Noortje, Rutten-Jacobs, Loes, Samson, Yves, Kramer, Jamie, Malik, Shaneela, Brott, Thomas G, Brown, Robert D, Singleton, Andrew, Hardy, John, Rich, Stephen S, Tanislav, Christian, Jungehülsing, Jan, Abboud, Shérine, Béjot, Yannick, Caso, Valeria, Bersano, Anna, Gschwendtner, Andreas, Metso, Tiina M, Sessa, Maria, Cole, John, Lamy, Chantal, Medeiros, Elisabeth, Beretta, Simone, Bonati, Leo H, Grau, Armin J, Michel, Patrik, Majersik, Jennifer J, Sharma, Pankaj, Kloss, Manja, Kalashnikova, Ludmila, Nazarova, Maria, Dobrynina, Larisa, Bartels, Eva, Guillon, Benoit, van den Herik, Evita G, Fernandez-Cadenas, Israel, Jood, Katarina, Nalls, Michael A, De Leeuw, Frank-Erik, Chauhan, Ganesh, Jern, Christina, Cheng, Yu-Ching, Werner, Inge, Metso, Antti J, Lichy, Christoph, Lyrer, Philippe A, Brandt, Tobias, Boncoraglio, Giorgio B, Wichmann, Heinz-Erich, Gieger, Christian, Engelter, Stefan T, Johnson, Andrew D, Böttcher, Thomas, Castellano, Maurizio, Arveiler, Dominique, Ikram, M Arfan, Breteler, Monique M B, Padovani, Alessandro, Meschia, James F, Kuhlenbäumer, Gregor, Rolfs, Arndt, Pezzini, Alessandro, Worrall, Bradford B, Consortium, International Stroke Genetics, Ringelstein, Erich-Bernd, Zelenika, Diana, Tatlisumak, Turgut, Lathrop, Mark, Leys, Didier, Amouyel, Philippe, Dallongeville, Jean, Group, CADISP, Thijs, Vincent, Lemmens, Robin, Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean-Louis, Deltour, Sandrine, Leder, Sara, Léger, Anne, Canaple, Sandrine, Godefroy, Olivier, Markus, Hugh S, Giroud, Maurice, Jacquin, Agnès, Moulin, Thierry, Vullier, Fabrice, Tzourio, Christophe, Dos Santos, Michael, Malik, Rainer, Hausser, Ingrid, Thomas-Feles, Constanze, Weber, Ralf, Dichgans, Martin, Grond-Ginsbach, Caspar, Hacke, Werner, Giossi, Alessia, Volonghi, Irene, Costa, Paolo, del Zotto, Elisabetta, Morotti, Andrea, Poli, Loris, Lorenza Muiesan, Maria, Salvetti, Massimo, Epidémiologie des maladies chroniques: impact des intéractions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Epidemiologie-Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Helsinki University Central Hospital [Finland] (HUCH), Heidelberg University Hospital [Heidelberg], University Hospital Basel [Basel], Università degli Studi di Brescia = University of Brescia (UniBs), University Hospitals Leuven [Leuven], Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), University of Cambridge [UK] (CAM), Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), University of Virginia, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Neurochirurgie Expérimentale [Brussels] (ULB 257), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Perugia = University of Perugia (UNIPG), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Ospedale San Raffaele, University of Maryland School of Medicine, University of Maryland System, Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Klinikum Ludwigshafen [Germany], Service of Neurology [CHUV, Lausanne, Switzerland], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Utah School of Medicine [Salt Lake City], Institute of Cardiovascular Research (ICR2UL), Royal Holloway [University of London] (RHUL), Ashford and St Peter's hospitals NHS foundation trust, Russian Academy of Sciences [Moscow] (RAS), Centre for Cognition and Decision Making [HSE, Moscow], Institut of Cognitive Neuroscience [HSE, Moscow] (ICN), Vysšaja škola èkonomiki = National Research University Higher School of Economics [Moscow] (HSE)-Vysšaja škola èkonomiki = National Research University Higher School of Economics [Moscow] (HSE), Zentrum für neurologische Gefäßdiagnostik - Center for Neurological Vascular Diagnostics [Munich, Germany], Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Department of Neurology [Erasmus MC, Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital Universitario Mutua de Terrassa, Vall d'Hebron University Hospital [Barcelona], Insitute of Neuroscience and Physiology, University of Gothenburg (GU), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Schmieder Klinik [Heidelberg, Germany], Helmholtz Zentrum München = German Research Center for Environmental Health, Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University Hospital Rostock, Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Brescia, Mayo Clinic [Jacksonville], Institute of Experimental Medicine - Institut für Experimentelle Medizin [Kiel, Germany] (IEM), Christian-Albrechts-Universität zu Kiel (CAU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, McGill University and Genome Quebec Innovation Centre, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Pharmacologie de la mort neuronale et de la plasticité cérébrale, IFR114-Université de Lille, Droit et Santé, Réseau International des Instituts Pasteur (RIIP), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, The CADISP study has been supported by INSERM, Lille 2 University, Institut Pasteur de Lille and Lille University Hospital and received funding from the European Regional Development Fund (FEDER funds) and Région Nord-Pas-de-Calais in the framework of Contrat de Projets Etat-Region 2007–2013 Région Nord-Pas-de-Calais (grant 09120030), Centre National de Génotypage, the Emil Aaltonen Foundation, the Paavo Ilmari Ahvenainen Foundation, the Helsinki University Central Hospital Research Fund, the Helsinki University Medical Foundation, the Päivikki and Sakari Sohlberg Foundation, the Aarne Koskelo Foundation, the Maire Taponen Foundation, the Aarne and Aili Turunen Foundation, the Lilly Foundation, the Alfred Kordelin Foundation, the Finnish Medical Foundation, the Orion Farmos Research Foundation, the Maud Kuistila Foundation, the Finnish Brain Foundation, the Biomedicum Helsinki Foundation, Projet Hospitalier de Recherche Clinique Régional, Fondation de France, Génopôle de Lille, Adrinord, the Basel Stroke Funds, the Käthe-Zingg-Schwichtenberg-Fonds of the Swiss Academy of Medical Sciences and the Swiss Heart Foundation.L.H.B., S.T.E. and P.A.L. were supported, in part, by a grant from the Swiss National Science Foundation (33CM30-124119). S.D. is supported by a Chair of Excellence from the French National Research Agency (ANR). S.D. and M.D. are supported by a grant from the Leducq Foundation. M.D. is supported by the Vascular Dementia Research Foundation. I.F.-C. is supported by the Miguel Servet programme (CP12/03298) from the Spanish Ministry of Health (Instituto de Salud Carlos III). G.K. is a member of the Deutsche Forschungsgemeinschaft Cluster of Excellence 'Inflammation at Interfaces'. P.S. is supported by a Department of Health (UK) senior fellowship. A.M.S. is supported by the American Heart Association/American Stroke Association National Clinical Research Program (AHA 3CRP14140001). V.T. is supported by Fonds Wetenschappelijk Onderzoek Flanders., CADISP Group, RIKEN Center for Integrative Medical Science, Università degli Studi di Brescia [Brescia], University of Virginia [Charlottesville], Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpêtrière]], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de Neurologie Expérimentale [ULB, Brussels, Belgium] (ULB 257), Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Università degli Studi di Perugia (UNIPG), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), National Research University Higher School of Economics [Moscow] (HSE)-National Research University Higher School of Economics [Moscow] (HSE), Radboud university [Nijmegen], Helmholtz-Zentrum München (HZM), Westfälische Wilhelms-Universität Münster (WWU), The authors thank the staff and participants of all CADISP centers for their important contributions., Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpétriêre], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation Jean Dausset-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Erasmus MC other, Epidemiology, Debette, S, Kamatani, Y, Metso, T, Kloss, M, Chauhan, G, Engelter, S, Pezzini, A, Thijs, V, Markus, H, Dichgans, M, Wolf, C, Dittrich, R, Touzé, E, Southerland, A, Samson, Y, Abboud, S, Béjot, Y, Caso, V, Bersano, A, Gschwendtner, A, Sessa, M, Cole, J, Lamy, C, Medeiros, E, Beretta, S, Bonati, L, Grau, A, Michel, P, Majersik, J, Sharma, P, Kalashnikova, L, Nazarova, M, Dobrynina, L, Bartels, E, Guillon, B, Van Den Herik, E, Fernandez Cadenas, I, Jood, K, Nalls, M, De Leeuw, F, Jern, C, Cheng, Y, Werner, I, Metso, A, Lichy, C, Lyrer, P, Brandt, T, Boncoraglio, G, Wichmann, H, Gieger, C, Johnson, A, Böttcher, T, Castellano, M, Arveiler, D, Ikram, M, Breteler, M, Padovani, A, Meschia, J, Kuhlenbäumer, G, Rolfs, A, Worrall, B, Ringelstein, E, Zelenika, D, Tatlisumak, T, Lathrop, M, Leys, D, Amouyel, P, Dallongeville, J, Lemmens R, P, and Ferrarese, C

Subjects
Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Myocardial Infarction, Genome-wide association study, Carotid Artery, Internal, Dissection, Gastroenterology, epidemiology [Carotid Artery, Internal, Dissection], Brain Ischemia, 0302 clinical medicine, Migraine Disorder, Odds Ratio, Finland, Vertebral Artery Dissection, 0303 health sciences, education.field_of_study, epidemiology [Hypercholesterolemia], MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, Phactr-1 protein, human, MESH: Brain Ischemia, MESH: Follow-Up Studies, 3. Good health, MESH: Myocardial Infarction, Human, medicine.medical_specialty, Migraine Disorders, Hypercholesterolemia, MESH: Vertebral Artery Dissection, Lower risk, genetics [Brain Ischemia], Article, Follow-Up Studie, MESH: Carotid Artery, Internal, Dissection, 03 medical and health sciences, Genetic, SDG 3 - Good Health and Well-being, genetics [Carotid Artery, Internal, Dissection], Genetics, Genetic predisposition, epidemiology [Brain Ischemia], Humans, epidemiology [Vertebral Artery Dissection], Polymorphism, education, Alleles, MESH: Humans, genetics [Vertebral Artery Dissection], MESH: Adult, Odds ratio, Microfilament Protein, medicine.disease, Adult, Female, Follow-Up Studies, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Hypertension, Microfilament Proteins, Middle Aged, Obesity, Risk Factors, Polymorphism, Single Nucleotide, MESH: Genome-Wide Association Study, Carotid Artery, MESH: Female, 030217 neurology & neurosurgery, epidemiology [Finland], Cervical Artery, Vertebral artery dissection, epidemiology [Hypertension], MESH: Hypertension, MESH: Risk Factors, MESH: Obesity, Stroke, Allele, Dissection, MESH: Finland, MESH: Genetic Predisposition to Disease, MESH: Hypercholesterolemia, Single Nucleotide, MESH: Migraine Disorders, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], epidemiology [Myocardial Infarction], [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Population, MESH: Genetic Pleiotropy, physiology [Microfilament Proteins], Biology, MESH: Microfilament Proteins, Internal medicine, ddc:570, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, 030304 developmental biology, epidemiology [Obesity], Risk Factor, MESH: Alleles, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Internal, MESH: Odds Ratio, MESH: Male, epidemiology [Migraine Disorders], genetics [Microfilament Proteins]
Abstract

Item does not contain fulltext Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 x 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 x 10(-3); combined P = 1.00 x 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.

Published
2015

47. Preparation, Characterization And Latent Heat Thermal Energy Storage Properties Of Micro-Nanoencapsulated Fatty Acids By Polystyrene Shell

Author

Sari, Ahmet, Alkan, Cemil, and Altintas, Ayse

Abstract

This work deals with the synthesis, physico-chemical characterization and latent heat thermal energy storage (LHTES) properties of micro-nanoencapsulated capric, lauric and myristic acids with polystyrene (PS) by using emulsion polymerization method. In synthesized micro-nanocapsules, the fatty acid has a function of phase change material (PCM) while PS acts as a shell material. The micro-nanoencapsulated PCMs (M-NEPCMs) were characterized chemically and morphologically by using Fourier transform infrared (FT-IR) spectroscopy, particle size distribution (PSD), and polarized optical microscopy (POM) and scanning electron microscopy (SEM) analyses methods. Differential scanning calorimeter (DSC) analysis showed that the fabricated M-NEPCMs melt and freeze in the temperature range of 22-48 degrees C and 19-49 degrees C as they storage and release a latent heat in range of 87-98 J/g and (-84) J/g (-96) J/g. The M-NEPCMs were subjected to a thermal cycling test consisted with 5000 heating/cooling processes and the results revealed that their LHTES properties were changed slightly. The M-NEPCMs had good thermal durability and reasonable thermal conductivity values. These advantageous properties make them potential LHTES materials for thermal regulating, solar heat pumps and solar space heating cooling applications in buildings. (C) 2014 Elsevier Ltd. All rights reserved.

Published
2014

49. 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
Full Text
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50. 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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