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{ "count": 24593, "next": "http://api.gregory-ms.com/articles/?format=api&page=1554", "previous": "http://api.gregory-ms.com/articles/?format=api&page=1552", "results": [ { "article_id": 380812, "title": "Pathological cut-offs of global and regional brain volume loss in multiple sclerosis", "summary": "<jats:sec><jats:title>Background:</jats:title><jats:p> Volumetric MRI surrogate markers of disease progression are lacking. </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> To establish cut-off values of brain volume loss able to discriminate between healthy controls and MS patients. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> In total, 386 patients after first demyelinating event suggestive of MS (CIS), 964 relapsing-remitting MS (RRMS) patients, 63 secondary-progressive MS (SPMS) patients and 58 healthy controls were included in this longitudinal study. A total of 11,438 MRI scans performed on the same MRI scanner with the same protocol were analysed. Annualised percentage changes of whole brain, grey matter, thalamus and corpus callosum volumes were estimated. We investigated cut-offs able to discriminate between healthy controls and MS patients. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> At a predefined specificity of 90%, the annualised percentage change cut-off of corpus callosum volume (−0.57%) was able to distinguish between healthy controls and patients with the highest sensitivity (51% in CIS, 48% in RRMS and 42% in SPMS patients). Lower sensitivities (22%−49%) were found for cut-offs of whole brain, grey matter and thalamic volume loss. Among CIS and RRMS patients, cut-offs were associated with greater accumulation of disability. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> We identified cut-offs of annualised global and regional brain volume loss rates able to discriminate between healthy controls and MS patients. </jats:p></jats:sec>", "link": "http://journals.sagepub.com/doi/pdf/10.1177/1352458517742739", "published_date": "2017-11-16T00:00:00Z", "sources": [ "SAGE Publications" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "SAGE Publications", "container_title": "Multiple Sclerosis Journal", "authors": [ { "author_id": 149329, "given_name": "Maria Pia", "family_name": "Sormani", "ORCID": "http://orcid.org/0000-0001-6892-104X", "country": null }, { "author_id": 322818, "given_name": "Eva Kubala", "family_name": "Havrdova", "ORCID": "http://orcid.org/0000-0002-9543-4359", "country": null }, { "author_id": 241018, "given_name": "Dana", "family_name": "Horakova", "ORCID": null, "country": null }, { "author_id": 151316, "given_name": "Tomas", "family_name": "Uher", "ORCID": "http://orcid.org/0000-0003-3160-9022", "country": null }, { "author_id": 317884, "given_name": "Manuela", "family_name": "Vaneckova", "ORCID": "http://orcid.org/0000-0002-8784-7997", "country": null }, { "author_id": 322817, "given_name": "Jan", "family_name": "Krasensky", "ORCID": "http://orcid.org/0000-0002-5605-8821", "country": null }, { "author_id": 213444, "given_name": "Lukas", "family_name": "Sobisek", "ORCID": "http://orcid.org/0000-0001-8071-2005", "country": null }, { "author_id": 268747, "given_name": "Michaela", "family_name": "Tyblova", "ORCID": null, "country": null }, { "author_id": 304969, "given_name": "Jana", "family_name": "Volna", "ORCID": null, "country": null }, { "author_id": 273476, "given_name": "Zdenek", "family_name": "Seidl", "ORCID": null, "country": null }, { "author_id": 143256, "given_name": "Niels", "family_name": "Bergsland", "ORCID": "http://orcid.org/0000-0002-7792-0433", "country": null }, { "author_id": 147934, "given_name": "Michael G", "family_name": "Dwyer", "ORCID": "http://orcid.org/0000-0003-4684-4658", "country": null }, { "author_id": 143251, "given_name": "Robert", "family_name": "Zivadinov", "ORCID": "http://orcid.org/0000-0002-7799-1485", "country": null }, { "author_id": 150517, "given_name": "Nicola", "family_name": "De Stefano", "ORCID": "http://orcid.org/0000-0003-4930-7639", "country": "IT" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2022-05-31T16:16:47.188873Z", "noun_phrases": [ "Pathological cut-offs", "global and regional brain volume loss", "multiple sclerosis" ], "doi": "10.1177/1352458517742739", "access": "restricted", "takeaways": " In total, 386 patients after first demyelinating event suggestive of MS (CIS), 964 relapsing-remitting MS (RRMS) patients, 63 secondary-progressive MS patients and 58 healthy controls were included in this longitudinal study . Annualised percentage changes of whole brain, grey matter, thalamus and corpus callosum volumes were estimated .", "categories": [] }, { "article_id": 380697, "title": "World Health Organization Essential Medicines List: Multiple sclerosis disease-modifying therapies application", "summary": "<jats:sec><jats:title>Introduction:</jats:title><jats:p> The World Health Organization (WHO) publishes a biennial Essential Medicines List (EML) to assist governments in low-resource settings to prioritize their spending on medicines. Currently, no medicines on the EML have a multiple sclerosis (MS) indication. Multiple Sclerosis International Federation (MSIF) prepared an application for inclusion of MS disease-modifying therapies (DMTs) for the 2019 EML together with the regional Committees for Treatment and Research in Multiple Sclerosis (TRIMS) and the World Federation of Neurology. </jats:p></jats:sec><jats:sec><jats:title>Rationale:</jats:title><jats:p> The MSIF taskforce categorized 15 DMTs according to their efficacy and risk profiles to ensure the ability to treat as many different clinical scenarios as possible. Three DMTs were selected: glatiramer acetate, fingolimod, and ocrelizumab. </jats:p></jats:sec><jats:sec><jats:title>Outcome:</jats:title><jats:p> The WHO Expert Committee did not recommend the addition of any of the DMTs to the EML. They acknowledged the public health burden of MS, the need for effective and affordable MS medications, and the high volume of letters received in support of the application but requested a revised application. </jats:p></jats:sec><jats:sec><jats:title>Discussion:</jats:title><jats:p> Despite the negative outcome, the repeated recognition of MS as a global public health burden is sending a powerful message to governments globally that a range of affordable and good quality medications need to be available to health systems and people affected by MS. </jats:p></jats:sec>", "link": "http://journals.sagepub.com/doi/pdf/10.1177/1352458519898340", "published_date": "2020-01-16T00:00:00Z", "sources": [ "SAGE Publications" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "SAGE Publications", "container_title": "Multiple Sclerosis Journal", "authors": [ { "author_id": 262133, "given_name": "Jennifer", "family_name": "McDonell", "ORCID": null, "country": null }, { "author_id": 241128, "given_name": "Kathleen", "family_name": "Costello", "ORCID": null, "country": null }, { "author_id": 179322, "given_name": "Joanna", "family_name": "Laurson-Doube", "ORCID": "http://orcid.org/0000-0001-9619-9170", "country": "GB" }, { "author_id": 262137, "given_name": "Nick", "family_name": "Rijke", "ORCID": null, "country": null }, { "author_id": 143429, "given_name": "Gavin", "family_name": "Giovannoni", "ORCID": "http://orcid.org/0000-0001-9995-1700", "country": null }, { "author_id": 241675, "given_name": "Brenda", "family_name": "Banwell", "ORCID": null, "country": null }, { "author_id": 224462, "given_name": "Peer", "family_name": "Baneke", "ORCID": "http://orcid.org/0000-0003-1271-4222", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2022-05-31T16:16:47.188873Z", "noun_phrases": [ "World Health Organization Essential Medicines List", "Multiple sclerosis disease-modifying therapies application" ], "doi": "10.1177/1352458519898340", "access": "open", "takeaways": " Multiple Sclerosis International Federation (MSIF) prepared an application for inclusion of MS disease-modifying therapies (DMTs) for the 2019 EML . Three DMTs were selected: glatiramer acetate, fingolimod, and ocrelizumab .", "categories": [] }, { "article_id": 381125, "title": "New insights into the burden and costs of multiple sclerosis in Europe: Results for France", "summary": "<jats:sec><jats:title>Introduction:</jats:title><jats:p> To estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. </jats:p></jats:sec><jats:sec><jats:title>Objectives and methods:</jats:title><jats:p> This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, in the societal perspective, in EUR 2015. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> A total of 491 patients (mean age 47 years) participated; 82% were below retirement age, and of these 56% were employed. Employment was related to disease severity, and MS affected productivity at work for 90% of patients. Overall, 95% and 67% of patients experienced fatigue and cognition as a problem, respectively. The mean utility and annual costs were 0.735 and €22,600 at Expanded Disability Status Scale (EDSS) 0–3, 0.500 and €38,100 at EDSS 4–6.5, and 0.337 and €48,100 at EDSS 7–9, respectively. The average cost of a relapse was estimated at €2300. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> This study provides current data on MS in France that are important for developments of health policies and to estimate the value of current and future treatments. </jats:p></jats:sec>", "link": "http://journals.sagepub.com/doi/pdf/10.1177/1352458517708125", "published_date": "2017-06-23T00:00:00Z", "sources": [ "SAGE Publications" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "SAGE Publications", "container_title": "Multiple Sclerosis Journal", "authors": [ { "author_id": 241146, "given_name": "Christine", "family_name": "Lebrun-Frenay", "ORCID": null, "country": null }, { "author_id": 252955, "given_name": "Gisela", "family_name": "Kobelt", "ORCID": null, "country": null }, { "author_id": 257822, "given_name": "Jenny", "family_name": "Berg", "ORCID": null, "country": null }, { "author_id": 257823, "given_name": "Daniela", "family_name": "Capsa", "ORCID": null, "country": null }, { "author_id": 272755, "given_name": "Mia", "family_name": "Gannedahl", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2022-05-31T16:16:47.188873Z", "noun_phrases": [ "New insights", "the burden", "costs", "multiple sclerosis", "Europe", "Results", "France" ], "doi": "10.1177/1352458517708125", "access": "open", "takeaways": " The average cost of a relapse was estimated at €2300. MS affected productivity at work for 90% of patients . The mean utility and annual costs were 0.735 and €22,600 at Expanded Disability Status Scale .", "categories": [] }, { "article_id": 380572, "title": "Single-subject structural cortical networks in clinically isolated syndrome", "summary": "<jats:sec><jats:title>Background:</jats:title><jats:p> Structural cortical networks (SCNs) represent patterns of coordinated morphological modifications in cortical areas, and they present the advantage of being extracted from previously acquired clinical magnetic resonance imaging (MRI) scans. SCNs have shown pathophysiological changes in many brain disorders, including multiple sclerosis. </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> To investigate alterations of SCNs at the individual level in patients with clinically isolated syndrome (CIS), thereby assessing their clinical relevance. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We analyzed baseline data collected in a prospective multicenter (MAGNIMS) study. CIS patients ( n = 60) and healthy controls ( n = 38) underwent high-resolution 3T MRI. Measures of disability and cognitive processing were obtained for patients. Single-subject SCNs were extracted from brain 3D-T1 weighted sequences; global and local network parameters were computed. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Compared to healthy controls, CIS patients showed altered small-world topology, an efficient network organization combining dense local clustering with relatively few long-distance connections. These disruptions were worse for patients with higher lesion load and worse cognitive processing speed. Alterations of centrality measures and clustering of connections were observed in specific cortical areas in CIS patients when compared with healthy controls. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Our study indicates that SCNs can be used to demonstrate clinically relevant alterations of connectivity in CIS. </jats:p></jats:sec>", "link": "http://journals.sagepub.com/doi/pdf/10.1177/1352458519865739", "published_date": "2019-07-24T00:00:00Z", "sources": [ "SAGE Publications" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "SAGE Publications", "container_title": "Multiple Sclerosis Journal", "authors": [ { "author_id": 172571, "given_name": "Sara", "family_name": "Collorone", "ORCID": "http://orcid.org/0000-0003-1506-8983", "country": null }, { "author_id": 147562, "given_name": "Ferran", "family_name": "Prados", "ORCID": "http://orcid.org/0000-0002-7872-0142", "country": null }, { "author_id": 260914, "given_name": "Marloes HJ", "family_name": "Hagens", "ORCID": null, "country": null }, { "author_id": 143326, "given_name": "Carmen", "family_name": "Tur", "ORCID": "http://orcid.org/0000-0003-1849-3184", "country": null }, { "author_id": 149986, "given_name": "Baris", "family_name": "Kanber", "ORCID": "http://orcid.org/0000-0003-2443-8800", "country": null }, { "author_id": 280110, "given_name": "Carole H", "family_name": "Sudre", "ORCID": null, "country": null }, { "author_id": 219263, "given_name": "Carsten", "family_name": "Lukas", "ORCID": "http://orcid.org/0000-0002-8562-9697", "country": null }, { "author_id": 169915, "given_name": "Claudio", "family_name": "Gasperini", "ORCID": "http://orcid.org/0000-0002-3959-4067", "country": null }, { "author_id": 150219, "given_name": "Celia", "family_name": "Oreja-Guevara", "ORCID": "http://orcid.org/0000-0002-9221-5716", "country": null }, { "author_id": 280112, "given_name": "Micaela", "family_name": "Andelova", "ORCID": null, "country": null }, { "author_id": 154922, "given_name": "Olga", "family_name": "Ciccarelli", "ORCID": "http://orcid.org/0000-0001-7485-1367", "country": "GB" }, { "author_id": 247101, "given_name": "Mike P", "family_name": "Wattjes", "ORCID": null, "country": null }, { "author_id": 252854, "given_name": "Sebastian", "family_name": "Ourselin", "ORCID": null, "country": null }, { "author_id": 254344, "given_name": "Daniel R", "family_name": "Altmann", "ORCID": null, "country": null }, { "author_id": 154471, "given_name": "Betty M", "family_name": "Tijms", "ORCID": "http://orcid.org/0000-0002-2612-1797", "country": null }, { "author_id": 143261, "given_name": "Frederik", "family_name": "Barkhof", "ORCID": "http://orcid.org/0000-0003-3543-3706", "country": null }, { "author_id": 260921, "given_name": "Ahmed T", "family_name": "Toosy", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2022-05-31T16:16:47.188873Z", "noun_phrases": [ "Single-subject structural cortical networks", "clinically isolated syndrome" ], "doi": "10.1177/1352458519865739", "access": "open", "takeaways": " Structural cortical networks (SCNs) represent patterns of coordinated morphological modifications in cortical areas . SCNs have shown pathophysiological changes in many brain disorders, including multiple sclerosis . CIS patients showed altered small-world topology, an efficient network organization combining dense local clustering with relatively few long-distance connections .", "categories": [] }, { "article_id": 380485, "title": "Predictive value of optical coherence tomography, multifocal visual evoked potentials, and full-field visual evoked potentials of the fellow, non-symptomatic eye for subsequent multiple sclerosis development in patients with acute optic neuritis", "summary": "<jats:sec><jats:title>Background:</jats:title><jats:p> Diagnosis of multiple sclerosis (MS) may sometimes be ascertained at the time of optic neuritis (ON) but other times require the advent of new disease activity. </jats:p></jats:sec><jats:sec><jats:title>Objectives:</jats:title><jats:p> The aim of this study was to examine the predictive value of optical coherence tomography (OCT) and visual evoked potential (VEP) measurements of the non-symptomatic, fellow eye of ON patients, for conversion to MS. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> This is a prospective cohort study in patients with acute ON. OCT thickness measurements of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer–inner plexiform layer (GCLIPL), and multifocal (mf) VEP and full-field (ff) VEP, were performed. Univariate and multivariate Cox regression examined the value of predictors for the conversion to MS. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> A total of 79 unilateral, acute ON patients, with no MS diagnosis or prior demyelination, were included. Of which, 28 patients developed MS during follow-up. Inferonasal GCLIPL, mean GCLIPL, and pRNFL thickness significantly predicted MS development in multivariate analysis (hazard ratio (HR) = 0.922–0.939, p = 0.0172–0.021). MfVEP mean latency (HR = 1.052, p = 0.006) only predicted MS conversion in univariate analysis. No significant predictive value was shown for the other parameters ( p > 0.2). </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> While both mfVEP and OCT are useful tools in the evaluation of acute ON patients, only OCT measurements of fellow eyes may serve as an independent predictor of MS development. </jats:p></jats:sec>", "link": "http://journals.sagepub.com/doi/pdf/10.1177/1352458520917924", "published_date": "2020-06-08T00:00:00Z", "sources": [ "SAGE Publications" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "SAGE Publications", "container_title": "Multiple Sclerosis Journal", "authors": [ { "author_id": 210684, "given_name": "Gorm", "family_name": "Pihl-Jensen", "ORCID": "http://orcid.org/0000-0002-2596-9358", "country": null }, { "author_id": 256637, "given_name": "Benedikte", "family_name": "Wanscher", "ORCID": null, "country": null }, { "author_id": 160457, "given_name": "Jette Lautrup", "family_name": "Frederiksen", "ORCID": "http://orcid.org/0000-0003-1661-7438", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2022-05-31T16:16:47.188873Z", "noun_phrases": [ "Predictive value", "optical coherence tomography", "multifocal visual evoked potentials", "full-field visual evoked potentials", "the fellow, non-symptomatic eye", "subsequent multiple sclerosis development", "patients", "acute optic neuritis" ], "doi": "10.1177/1352458520917924", "access": "restricted", "takeaways": " The aim of this study was to examine the predictive value of optical coherence tomography (OCT) and visual evoked potential (VEP) measurements of the non-symptomatic, fellow eye of ON patients, for conversion to MS . A total of 79 unilateral, acute ON patients with no MS diagnosis or prior demyelination were included .", "categories": [] }, { "article_id": 381985, "title": "Prolactin in multiple sclerosis", "summary": "<jats:p> Multiple sclerosis (MS) is more common among women than men. MS often goes into remission during pregnancy, when prolactin (PRL) levels are known to be high. In an animal model of demyelination, PRL promoted myelin repair, suggesting it has potential as a remyelinating therapy in MS. In this systematic review, we examined the known associations between PRL and MS, in order to elucidate its potential role in the pathophysiology and treatment of MS. A systematic search was performed in the electronic databases PubMed and EMBASE, using the keywords \"prolactin\" AND “multiple sclerosis.” The inclusion criteria were met by 23 studies. These studies suggested to us that elevated PRL may be more common in MS patients than in controls. Hyperprolactinemia may also be associated with clinical relapse in MS, especially among patients with hypothalamic lesions or optic neuritis; however, it is unknown if this is a cause or consequence of a relapse. Overall, most people with MS have normal PRL levels. The impact of PRL on MS outcomes remains unclear. </jats:p>", "link": "https://journals.sagepub.com/doi/full/10.1177/1352458512461391", "published_date": "2012-08-29T00:00:00Z", "sources": [ "SAGE Publications" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "SAGE Publications", "container_title": "Multiple Sclerosis Journal", "authors": [ { "author_id": 296822, "given_name": "Simon", "family_name": "Zhornitsky", "ORCID": null, "country": null }, { "author_id": 247221, "given_name": "V Wee", "family_name": "Yong", "ORCID": null, "country": null }, { "author_id": 299412, "given_name": "Samuel", "family_name": "Weiss", "ORCID": null, "country": null }, { "author_id": 241769, "given_name": "Luanne M", "family_name": "Metz", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2022-05-31T16:16:47.188873Z", "noun_phrases": [ "Prolactin", "multiple sclerosis" ], "doi": "10.1177/1352458512458555", "access": "open", "takeaways": " MS often goes into remission during pregnancy, when prolactin (PRL) levels are known to be high . In an animal model of demyelination, PRL promoted myelin repair, suggesting it has potential as a remyelinating therapy in MS . Hyperprolactinemia may also be associated with clinical relapse in MS, especially among patients with hypothalamic lesions .", "categories": [] }, { "article_id": 380307, "title": "Longitudinal analysis of T1w/T2w ratio in patients with multiple sclerosis from first clinical presentation", "summary": "<jats:sec><jats:title>Background:</jats:title><jats:p> Cross-sectional studies suggest normal appearing white matter (NAWM) integrity loss may lead to cortical atrophy in late-stage relapsing-remitting multiple sclerosis (MS). </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> To investigate the relationship between NAWM integrity and cortical thickness from first clinical presentation longitudinally. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> NAWM integrity and cortical thickness were assessed with 3T magnetic resonance imaging (MRI) in 102 patients with clinically isolated syndrome or early MS (33.2 (20.1–60.1) years old, 68% female) from first clinical presentation over 2.8 ± 1.6 years. Fifty healthy controls (HCs) matched for age and sex were included. NAWM integrity was evaluated using the standardized T1w/T2w ratio (sT1w/T2w). The association between sT1w/T2w and cortical thickness was assessed using linear mixed models. The effect of disease activity was investigated using the No Evidence of Disease Activity (NEDA-3) criteria. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> At baseline, sT1w/T2w ( p = 0.152) and cortical thickness ( p = 0.489) did not differ from HCs. Longitudinally, decreasing sT1w/T2w was associated with cortical thickness and increasing lesion burden (marginal R<jats:sup>2</jats:sup> = 0.061). The association was modulated by failing NEDA-3 (marginal R<jats:sup>2</jats:sup> = 0.097). </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> sT1w/T2w may be a useful MRI biomarker for early MS, detecting relevant NAWM damage over time using conventional MRI scans, although with less sensitivity compared to quantitative measures. </jats:p></jats:sec>", "link": "http://journals.sagepub.com/doi/pdf/10.1177/13524585211003479", "published_date": "2021-04-15T00:00:00Z", "sources": [ "SAGE Publications" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "SAGE Publications", "container_title": "Multiple Sclerosis Journal", "authors": [ { "author_id": 180813, "given_name": "Graham", "family_name": "Cooper", "ORCID": "http://orcid.org/0000-0001-8383-6476", "country": "DE" }, { "author_id": 143294, "given_name": "Claudia", "family_name": "Chien", "ORCID": "http://orcid.org/0000-0001-8280-9513", "country": null }, { "author_id": 237106, "given_name": "Hanna", "family_name": "Zimmermann", "ORCID": null, "country": null }, { "author_id": 143302, "given_name": "Judith", "family_name": "Bellmann-Strobl", "ORCID": "http://orcid.org/0000-0003-2615-1643", "country": null }, { "author_id": 156906, "given_name": "Klemens", "family_name": "Ruprecht", "ORCID": "http://orcid.org/0000-0003-1962-6014", "country": null }, { "author_id": 324714, "given_name": "Joseph", "family_name": "Kuchling", "ORCID": "http://orcid.org/0000-0002-7981-2073", "country": null }, { "author_id": 180814, "given_name": "Susanna", "family_name": "Asseyer", "ORCID": "http://orcid.org/0000-0001-6289-1791", "country": null }, { "author_id": 143296, "given_name": "Alexander U.", "family_name": "Brandt", "ORCID": "http://orcid.org/0000-0002-9768-014X", "country": "DE" }, { "author_id": 143295, "given_name": "Michael", "family_name": "Scheel", "ORCID": "http://orcid.org/0000-0002-3505-2914", "country": null }, { "author_id": 202091, "given_name": "Carsten", "family_name": "Finke", "ORCID": "http://orcid.org/0000-0002-7665-1171", "country": null }, { "author_id": 237109, "given_name": "Friedemann", "family_name": "Paul", "ORCID": "https://orcid.org/0000-0002-6378-0070", "country": "DE" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2022-05-31T16:16:47.188873Z", "noun_phrases": [ "Longitudinal analysis", "T1w/T2w ratio", "patients", "multiple sclerosis", "first clinical presentation" ], "doi": "10.1177/13524585211003479", "access": "open", "takeaways": " White matter (NAWM) integrity loss may lead to cortical atrophy in late-stage relapsing-remitting MS . NAWM integrity and cortical thickness were assessed with 3T magnetic resonance imaging (MRI) in 102 patients with clinically isolated syndrome or early MS (33.2 (20.1–60.1) years old) from first clinical presentation over 2.8 ± 1.6 years .", "categories": [] }, { "article_id": 380185, "title": "All Bruton’s tyrosine kinase inhibitors have similar efficacy and risks: No", "summary": "What lies between “first in class” and “best in class”? A turn of phrase, a long and winding road, a wealth of innovation and experience. Bruton’s tyrosine kinase inhibitors (BTKIs) are a novel class of molecules under investigation for treatment of multiple sclerosis (MS). BTKIs modulate both B-cells and myeloid cells, the latter through the Fcγ receptor. As small molecules, they can cross the blood–brain barrier and affect microglia in the central nervous system (CNS), thus offering the promise of potentially treating neurodegenerative aspects of MS as well as inflammatory activity. Individual agents currently in Phase III clinical trials for treatment of relapsing and progressive MS include evobrutinib, fenebrutinib, and tolebrutinib; in a Phase II trial, orelabrutinib; and in a Phase I trial, BIIB091. Evobrutinib, tolebrutinib, and orelabrutinib are all irreversible, covalent BTKIs, whereas fenebrutinib and BIIB091 are reversible, non-covalent agents.\n\nThere is good reason to believe that, among these therapies, a “best in class” molecule will emerge. We are only at the trailhead, but we already observe disparate selectivity, strength of Bruton’s tyrosine kinase (BTK) inhibition, binding mechanisms, and CNS penetrance across drugs. As we peer down the long and winding road ahead, we anticipate these features will translate into meaningful efficacy and safety differences across Phase III trials and eventually in real-world practice.\n\nSelectivity of BTKIs is essential to minimize off-target toxicity and potential for adverse events. Unlike cell depleting therapies, BTKIs rarely cause major reduction in lymphocytes or immunoglobulin levels and are associated with relatively low rates of secondary infection. However, the first generation BTKI, ibrutinib, approved for the treatment of B-cell malignancies in 2013, was linked to other concerning adverse events including cardiac arrhythmias, hemorrhage, hypertension, diarrhea, arthralgias, and fungal infections. Off-target effects of ibrutinib stem from its activity on other kinases such as epidermal growth factor receptor (EGFR) and Janus kinase 3 (JAK3). Adverse events were reduced, but not eliminated, with the more selective, second generation BTKI, acalabrutinib, with bleeding, neutropenia, and fungal infections still reported.\n\nThe BTKIs under investigation in MS are more selective, but continue to evince a range with tolebrutinib binding the greatest number of other kinases, and fenebrutinib and orelabrutinib being the most selective for BTK.1 Safety data from Phase II trials of evobrutinib and tolebrutinib have been reassuring, with common adverse events including headaches, nasopharyngitis, and mild liver function test (LFT) and lipase elevations.2,3 However, given the relatively small numbers enrolled and brief durations of these studies, we expect that in Phase III trials and clinical practice, selectivity will lead to differential side effect profiles among therapies, as we have seen with approved BTKIs.1,4\n\nMoreover, certain serious adverse events may be at least in part due to on-target BTK inhibition. Secondary bleeding, for example, is thought to arise from both BTK and TEC family inhibition.4 In a pooled analysis of studies of fenebrutinib in other diseases, bleeding or bruising was reported in 8%, although serious bleeding events were rare.5 The mechanism for fungal infection is incompletely understood but may be due to effects of BTK inhibition on the innate immune system.6 Previous experience with other MS drugs highlights need for vigilance for rare, but serious, adverse events that may emerge in the post-marketing era and further differentiate BTKIs.\n\nPharmacodynamics and kinetics are likely to play a crucial role in determining comparative efficacy. Strength of BTK inhibition varies across drugs. Greater concentrations of evobrutinib are required to achieve half maximal inhibitory concentration (IC50) compared to tolebrutinib and fenebrutinib.7 When studied in vitro, fenebrutinib achieved greater suppression of B-cells and myeloid cells compared to evobrutinib and tolebrutinib.8 Binding mechanism may prove critical to potential for drug resistance. Oncologists have identified mutations in cysteine 481, the binding pocket for covalent BTKIs, in patients on ibrutinib suffering cancer relapses.9 By avoiding cysteine 481 as a non-covalent agent, fenebrutinib may prove less vulnerable to this threat.\n\nThere is preliminary evidence that CNS penetration varies across BTKIs, with tolebrutinib demonstrating greater penetrance compared to evobrutinib and fenebrutinib.10 If degree of CNS penetrance proves key to adaptation of microglial responses, there would be expected advantages for treatment of progressive MS. In an exploratory analysis from the Phase IIb trial of tolebrutinib, tolebrutinib at 60 mg daily was found to reduce volume of slowly expanding lesions, which have been associated with activated microglia and disability accumulation in MS.3\n\nPrevention of disability progression remains the greatest unmet need in the MS therapeutic landscape, and ability to meet this endpoint could prove a pivotal point of distinction among BTKIs. Phase III trials underway in progressive MS include FENtrepid, comparing fenebrutinib to ocrelizumab in primary progressive multiple sclerosis (PPMS); PERSEUS, comparing tolebrutinib to placebo in PPMS; and HERCULES, comparing tolebrutinib to placebo in secondary progressive MS.\n\nIn Phase II clinical trials in relapsing MS, both evobrutinib and tolebrutinib strongly reduced new gadolinium-enhancing lesions.2,3 It is too early to distinguish BTKIs in relapsing MS on other endpoints such as relapse rate and disability progression. In separate Phase III, randomized, double-blind trials in relapsing MS, evobrutinib, fenebrutinib, and tolebrutinib will each be compared against teriflunomide. Although we cannot compare relapse rates directly across trials, the similar trial designs and parallel active comparator arms may allow for some inferences regarding comparative efficacy. In addition, further work is necessary to determine efficacy and safety of BTKIs in older and non-white patients. The mean age of participants in the tolebrutinib and evobrutinib Phase II trials was 37 and 42 years, respectively; 92% in the tolebrutinib and 100% in the evobrutinib trial were White.2,3\nThe Beatles might have asked: at the end of this long and winding road, will we find a door? BTKIs differ in important respects, including selectivity, strength of BTK inhibition, binding mechanisms, and CNS penetrance. We can expect that, with accumulating evidence and experience, we will arrive at a “best in class” molecule—and a door into the CNS—that will transform that long and winding road, perhaps, into a straight and steady path to treatment of progression in MS.\n\nDeclaration of Conflicting Interests\n\nThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.L.R. has received research support from the MS Society of Canada, Consortium of Multiple Sclerosis Centers, and Roche. She has received speaker or consultant fees from Alexion, Biogen, EMD Serono, Novartis, Roche, and Sanofi Aventis.\n\nFunding\n\nThe author(s) received no financial support for the research, authorship, and/or publication of this article.", "link": "https://journals.sagepub.com/doi/full/10.1177/13524585221091060", "published_date": "2022-04-18T00:00:00Z", "sources": [ "SAGE Publications" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "SAGE Publications", "container_title": "Multiple Sclerosis Journal", "authors": [ { "author_id": 148025, "given_name": "Dalia L", "family_name": "Rotstein", "ORCID": "http://orcid.org/0000-0002-7280-3684", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2022-05-31T16:16:47.188873Z", "noun_phrases": [ "All Bruton’s tyrosine kinase inhibitors", "similar efficacy", "risks" ], "doi": "10.1177/13524585221091060", "access": "open", "takeaways": "", "categories": [] }, { "article_id": 380570, "title": "Infratentorial and spinal cord lesions: Cumulative predictors of long-term disability?", "summary": "<jats:sec><jats:title>Objective:</jats:title><jats:p> The objective of the study was to determine whether early infratentorial and/or spinal cord lesions are long-term cumulative predictors of disability progression in multiple sclerosis (MS). </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We selected 153 MS patients from the longitudinal Amsterdam MS cohort. Lesion analysis was performed at baseline and year 2. Disability progression after 6 and 11 years was measured using the Expanded Disability Status Scale (EDSS) and EDSS-plus (including 25-foot walk and 9-hole peg test). Patients with spinal cord or infratentorial lesions were compared for the risk of 6- and 11-year disability progression to patients without spinal cord or infratentorial lesions, respectively. Subsequently, patients with lesions on both locations were compared to patients with only spinal cord or only infratentorial lesions. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Baseline spinal cord lesions show a higher risk of 6-year EDSS progression (odds ratio (OR): 3.6, p = 0.007) and EDSS-plus progression (OR: 2.5, p = 0.028) and 11-year EDSS progression (OR: 2.8, p = 0.047). Patients with both infratentorial and spinal cord lesions did not have a higher risk of 6-year disability progression than patients with only infratentorial or only spinal cord lesions. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> The presence of early spinal cord lesions seems to be a dominant risk factor of disability progression. Simultaneous presence of early infratentorial and spinal cord lesions did not undisputedly predict disability progression. </jats:p></jats:sec>", "link": "http://journals.sagepub.com/doi/pdf/10.1177/1352458519864933", "published_date": "2019-08-02T00:00:00Z", "sources": [ "SAGE Publications" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "SAGE Publications", "container_title": "Multiple Sclerosis Journal", "authors": [ { "author_id": 210004, "given_name": "Iris", "family_name": "Dekker", "ORCID": "http://orcid.org/0000-0002-8987-9212", "country": null }, { "author_id": 267944, "given_name": "Madeleine H", "family_name": "Sombekke", "ORCID": null, "country": null }, { "author_id": 211529, "given_name": "Lisanne J", "family_name": "Balk", "ORCID": "http://orcid.org/0000-0002-3915-0052", "country": null }, { "author_id": 243288, "given_name": "Jeroen JG", "family_name": "Geurts", "ORCID": null, "country": null }, { "author_id": 143261, "given_name": "Frederik", "family_name": "Barkhof", "ORCID": "http://orcid.org/0000-0003-3543-3706", "country": null }, { "author_id": 244952, "given_name": "Bernard MJ", "family_name": "Uitdehaag", "ORCID": null, "country": null }, { "author_id": 174010, "given_name": "Joep", "family_name": "Killestein", "ORCID": "http://orcid.org/0000-0002-6347-5957", "country": null }, { "author_id": 247101, "given_name": "Mike P", "family_name": "Wattjes", "ORCID": null, "country": null }, { "author_id": 333512, "given_name": "Bastiaan", "family_name": "Moraal", "ORCID": "http://orcid.org/0000-0003-4559-1118", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2022-05-31T16:16:47.188873Z", "noun_phrases": [ "Infratentorial and spinal cord lesions", "Cumulative predictors", "long-term disability" ], "doi": "10.1177/1352458519864933", "access": "open", "takeaways": " Lesion analysis was performed at baseline and year 2 . Disability progression after 6 and 11 years was measured using the Expanded Disability Status Scale (EDSS) and EDSS-plus . Baseline spinal cord lesions showed a higher risk of 6-year disability progression .", "categories": [] }, { "article_id": 382001, "title": "Inflammation inhibits GABA transmission in multiple sclerosis", "summary": "<jats:p> Abnormal glutamate-dependent synaptic excitation contributes to neuronal damage in multiple sclerosis (MS). Little is known about the involvement of the GABA system in this disorder. Here we found that cerebrospinal fluid (CSF) from MS patients with enhanced brain lesions on magnetic resonance imaging inhibited GABA transmission in mouse brain slices. Enhanced IL-1β neuronal action was responsible for this effect, because IL-1β receptor antagonist blocked, and exogenous IL-1β mimicked the synaptic effect of inflamed CSF. Our results provide evidence that focal inflammation in MS perturbs the cytokine milieu within the circulating CSF, resulting in diffuse GABAergic alteration in neurons. </jats:p>", "link": "https://journals.sagepub.com/doi/full/10.1177/1352458512461391", "published_date": "2012-03-14T00:00:00Z", "sources": [ "SAGE Publications" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "SAGE Publications", "container_title": "Multiple Sclerosis Journal", "authors": [ { "author_id": 240827, "given_name": "Silvia", "family_name": "Rossi", "ORCID": null, "country": null }, { "author_id": 240828, "given_name": "Valeria", "family_name": "Studer", "ORCID": null, "country": null }, { "author_id": 240829, "given_name": "Caterina", "family_name": "Motta", "ORCID": null, "country": null }, { "author_id": 240830, "given_name": "Valentina", "family_name": "De Chiara", "ORCID": null, "country": null }, { "author_id": 240831, "given_name": "Francesca", "family_name": "Barbieri", "ORCID": null, "country": null }, { "author_id": 240832, "given_name": "Giorgio", "family_name": "Bernardi", "ORCID": null, "country": null }, { "author_id": 169913, "given_name": "Diego", "family_name": "Centonze", "ORCID": "http://orcid.org/0000-0002-8390-8545", "country": "IT" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2022-05-31T16:16:47.188873Z", "noun_phrases": [ "Inflammation", "GABA transmission", "multiple sclerosis" ], "doi": "10.1177/1352458512440207", "access": "restricted", "takeaways": " Abnormal glutamate-dependent excitation contributes to neuronal damage in multiple sclerosis . Little is known about the involvement of the GABA system in this disorder . MS patients with enhanced brain lesions inhibited GABA transmission in mice .", "categories": [] } ] }