Article List
List all articles in the database by earliest discovery_date
GET /articles/?format=api&page=2453
{ "count": 24837, "next": "http://api.gregory-ms.com/articles/?format=api&page=2454", "previous": "http://api.gregory-ms.com/articles/?format=api&page=2452", "results": [ { "article_id": 321, "title": "Paediatric multiple sclerosis and antibody-associated demyelination: clinical, imaging, and biological considerations for diagnosis and care", "summary": "<h2>Summary</h2><p>The field of acquired CNS neuroimmune demyelination in children is transforming. Progress in assay development, refinement of diagnostic criteria, increased biological insights provided by advanced neuroimaging techniques, and high-level evidence for the therapeutic efficacy of biological agents are redefining diagnosis and care. Three distinct neuroimmune conditions—multiple sclerosis, myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (AQP4-NMOSD)—can now be distinguished, with evidence from humans and animal models supporting distinct pathobiological disease mechanisms. The development of highly effective therapies for adult-onset multiple sclerosis and AQP4-NMOSD that suppress relapse rate by more than 90% has motivated advocacy for trials in children. However, doing clinical trials is challenging because of the rarity of these conditions in the paediatric age group, necessitating new approaches to trial design, including age-based trajectory modelling based on phase 3 studies in adults. Despite these limitations, the future for children and adolescents living with multiple sclerosis, MOGAD, or AQP4-NMOSD is far brighter than in years past, and will be brighter still if successful therapies to promote remyelination, enhance neuroprotection, and remediate cognitive deficits can be further accelerated.</p>", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30432-4/fulltext", "published_date": "2021-02-01T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 159108, "given_name": "Giulia", "family_name": "Fadda", "ORCID": "http://orcid.org/0000-0001-9658-815X", "country": null }, { "author_id": 241673, "given_name": "Thais", "family_name": "Armangue", "ORCID": null, "country": null }, { "author_id": 210191, "given_name": "Yael", "family_name": "Hacohen", "ORCID": "http://orcid.org/0000-0001-8490-9657", "country": null }, { "author_id": 143340, "given_name": "Tanuja", "family_name": "Chitnis", "ORCID": "http://orcid.org/0000-0002-9897-4422", "country": null }, { "author_id": 241675, "given_name": "Brenda", "family_name": "Banwell", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Paediatric multiple sclerosis", "antibody-associated demyelination", "clinical, imaging, and biological considerations", "diagnosis", "care" ], "doi": "10.1016/S1474-4422(20)30432-4", "access": "open", "takeaways": " The field of acquired CNS neuroimmune demyelination in children is transforming . The development of highly effective therapies for adult-onset multiple sclerosis and AQP4-NMOSD that suppress relapse rate by more than 90% has motivated advocacy for trials in children .", "categories": [] }, { "article_id": 322, "title": "Tolerance-inducing medicines in autoimmunity: rheumatology and beyond", "summary": "<h2>Summary</h2><p>Autoimmunity is currently managed with generalised immunosuppression, which is associated with serious side-effects such as infection and cancer. An ideal treatment strategy would be to induce immune tolerance—ie, to reprogramme the immune system to stop recognising the host itself as a threat. Drug-free remission should follow such an intervention, representing a change in the approach to the treatment of autoimmune disease. Tolerance induction is achievable in animal models of autoimmunity but translation to the clinic has been slow. Nonetheless, progress has been made—eg, restoration of therapeutic responsiveness and drug-free remission have been achieved with stem cell transplantation in refractory autoimmunity, and significant delays in onset of type 1 diabetes in individuals at high risk have been achieved following a brief treatment with anti-CD3 monoclonal antibody. In the future, antigen-specific interventions should provide highly targeted, personalised approaches, avoiding generalised immunosuppression entirely. Such trials have already started, using both direct autoantigenic peptide administration, cellular therapies, and other modalities. In this Series paper, we discuss the history of immune tolerance induction with a focus on rheumatological disease while also highlighting essential data from other specialties. We propose key unanswered questions, which will be covered in other papers in this Series.</p>", "link": "https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30100-4/fulltext", "published_date": "2020-08-31T23:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Rheumatology", "authors": [ { "author_id": 241698, "given_name": "James A", "family_name": "Stanway", "ORCID": null, "country": null }, { "author_id": 241700, "given_name": "John D", "family_name": "Isaacs", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Tolerance-inducing medicines", "autoimmunity", "rheumatology" ], "doi": "10.1016/S2665-9913(20)30100-4", "access": "restricted", "takeaways": " Autoimmunity is currently managed with generalised immunosuppression, which is associated with serious side-effects such as infection and cancer . The ideal treatment strategy would be to induce immune tolerance, reprogramme the immune system to stop recognising the host itself as a threat . Tolerance induction is achievable in animal models but translation to the clinic has been slow .", "categories": [] }, { "article_id": 310, "title": "Neuroimaging manifestations in children with SARS-CoV-2 infection: a multinational, multicentre collaborative study", "summary": "<h2>Summary</h2><h3>Background</h3><p>The CNS manifestations of COVID-19 in children have primarily been described in case reports, which limit the ability to appreciate the full spectrum of the disease in paediatric patients. We aimed to identify enough cases that could be evaluated in aggregate to better understand the neuroimaging manifestations of COVID-19 in the paediatric population.</p><h3>Methods</h3><p>An international call for cases of children with encephalopathy related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and abnormal neuroimaging findings was made. Clinical history and associated plasma and cerebrospinal fluid data were requested. These data were reviewed by a central neuroradiology panel, a child neurologist, and a paediatric infectious diseases expert. The children were categorised on the basis of their time of probable exposure to SARS-CoV-2. In addition, cases were excluded when a direct link to SARS-CoV-2 infection could not be established or an established alternate diagnostic cause could be hypothesised. The accepted referral centre imaging data, from ten countries, were remotely reviewed by a central panel of five paediatric neuroradiologists and a consensus opinion obtained on the imaging findings.</p><h3>Findings</h3><p>38 children with neurological disease related to SARS-CoV-2 infection were identified from France (n=13), the UK (n=8), the USA (n=5), Brazil (n=4), Argentina (n=4), India (n=2), Peru (n=1), and Saudi Arabia (n=1). Recurring patterns of disease were identified, with neuroimaging abnormalities ranging from mild to severe. The most common imaging patterns were postinfectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients), myelitis (eight patients), and neural enhancement (13 patients). Cranial nerve enhancement could occur in the absence of corresponding neurological symptoms. Splenial lesions (seven patients) and myositis (four patients) were predominantly observed in children with multisystem inflammatory syndrome. Cerebrovascular complications in children were less common than in adults. Significant pre-existing conditions were absent and most children had favourable outcomes. However, fatal atypical CNS co-infections developed in four previously healthy children infected with SARS-CoV-2.</p><h3>Interpretation</h3><p>Acute-phase and delayed-phase SARS-CoV-2-related CNS abnormalities are seen in children. Recurring patterns of disease and atypical neuroimaging manifestations can be found and should be recognised being as potentially due to SARS-CoV-2 infection as an underlying aetiological factor. Studies of paediatric specific cohorts are needed to better understand the effects of SARS-CoV-2 infection on the CNS at presentation and on long-term follow-up in children.</p><h3>Funding</h3><p>American Society of Pediatric Neuroradiology, University of Manchester (Manchester, UK).</p><h3>Video Abstract</h3><p>Neuroimaging manifestations in children with SARS-CoV-2 infection</p>", "link": "https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30362-X/fulltext", "published_date": "2020-12-15T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Child & Adolescent Health", "authors": [ { "author_id": 277075, "given_name": "Camilla E", "family_name": "Lindan", "ORCID": null, "country": null }, { "author_id": 256312, "given_name": "Kshitij", "family_name": "Mankad", "ORCID": null, "country": null }, { "author_id": 190480, "given_name": "Dipak", "family_name": "Ram", "ORCID": "http://orcid.org/0000-0001-8544-2534", "country": null }, { "author_id": 277078, "given_name": "Larry K", "family_name": "Kociolek", "ORCID": null, "country": null }, { "author_id": 277080, "given_name": "V Michelle", "family_name": "Silvera", "ORCID": null, "country": null }, { "author_id": 277081, "given_name": "Nathalie", "family_name": "Boddaert", "ORCID": null, "country": null }, { "author_id": 277082, "given_name": "Stavros Michael", "family_name": "Stivaros", "ORCID": null, "country": null }, { "author_id": 277083, "given_name": "Susan", "family_name": "Palasis", "ORCID": null, "country": null }, { "author_id": 277084, "given_name": "Sameen", "family_name": "Akhtar", "ORCID": null, "country": null }, { "author_id": 277085, "given_name": "Douglas", "family_name": "Alden", "ORCID": null, "country": null }, { "author_id": 277086, "given_name": "Suraj", "family_name": "Amonkar", "ORCID": null, "country": null }, { "author_id": 277087, "given_name": "Pascale", "family_name": "Aouad", "ORCID": null, "country": null }, { "author_id": 277088, "given_name": "Mélodie", "family_name": "Aubart", "ORCID": null, "country": null }, { "author_id": 277089, "given_name": "Jose Alejandro", "family_name": "Bacalla", "ORCID": null, "country": null }, { "author_id": 277090, "given_name": "Alcino A", "family_name": "Barbosa", "ORCID": null, "country": null }, { "author_id": 277091, "given_name": "Romain", "family_name": "Basmaci", "ORCID": null, "country": null }, { "author_id": 277092, "given_name": "Laureline", "family_name": "Berteloot", "ORCID": null, "country": null }, { "author_id": 277093, "given_name": "Thomas", "family_name": "Blauwblomme", "ORCID": null, "country": null }, { "author_id": 215405, "given_name": "Gilles", "family_name": "Brun", "ORCID": "http://orcid.org/0000-0001-7076-1954", "country": null }, { "author_id": 277094, "given_name": "Olivia", "family_name": "Carney", "ORCID": null, "country": null }, { "author_id": 277095, "given_name": "Judith", "family_name": "Chareyre", "ORCID": null, "country": null }, { "author_id": 277096, "given_name": "Gérard", "family_name": "Chéron", "ORCID": null, "country": null }, { "author_id": 277098, "given_name": "Pablo Picasso De Araujo", "family_name": "Coimbra", "ORCID": null, "country": null }, { "author_id": 277099, "given_name": "Volodia", "family_name": "Dangouloff-Ros", "ORCID": null, "country": null }, { "author_id": 277100, "given_name": "Felice", "family_name": "D'Arco", "ORCID": null, "country": null }, { "author_id": 277101, "given_name": "Rob", "family_name": "Dineen", "ORCID": null, "country": null }, { "author_id": 277102, "given_name": "Loic", "family_name": "De-Pontual", "ORCID": null, "country": null }, { "author_id": 253018, "given_name": "Isabelle", "family_name": "Desguerre", "ORCID": null, "country": null }, { "author_id": 277103, "given_name": "Wissam", "family_name": "Elfallal", "ORCID": null, "country": null }, { "author_id": 277104, "given_name": "D. Gareth", "family_name": "Evans", "ORCID": null, "country": null }, { "author_id": 277105, "given_name": "Suely Fazio", "family_name": "Ferraciolli", "ORCID": null, "country": null }, { "author_id": 263671, "given_name": "Nadine", "family_name": "Girard", "ORCID": null, "country": null }, { "author_id": 277106, "given_name": "Fabrício Guimarães", "family_name": "Gonçalves", "ORCID": null, "country": null }, { "author_id": 277107, "given_name": "Ivan", "family_name": "Gonzalez", "ORCID": null, "country": null }, { "author_id": 277108, "given_name": "P. Ellen", "family_name": "Grant", "ORCID": null, "country": null }, { "author_id": 277109, "given_name": "David", "family_name": "Grévent", "ORCID": null, "country": null }, { "author_id": 277110, "given_name": "Carolina Valduga de Alencastro", "family_name": "Guimaraes", "ORCID": null, "country": null }, { "author_id": 264558, "given_name": "Jane", "family_name": "Hassell", "ORCID": null, "country": null }, { "author_id": 277112, "given_name": "Fabiana C.C.", "family_name": "Hirata", "ORCID": null, "country": null }, { "author_id": 277113, "given_name": "Ian", "family_name": "Kamaly-Asl", "ORCID": null, "country": null }, { "author_id": 277114, "given_name": "Jeffrey", "family_name": "Jacob", "ORCID": null, "country": null }, { "author_id": 277115, "given_name": "Kandise", "family_name": "Jackson", "ORCID": null, "country": null }, { "author_id": 277116, "given_name": "Blaise V.", "family_name": "Jones", "ORCID": null, "country": null }, { "author_id": 277117, "given_name": "Robin", "family_name": "Joseph", "ORCID": null, "country": null }, { "author_id": 277118, "given_name": "Ah Young", "family_name": "Jung", "ORCID": null, "country": null }, { "author_id": 277119, "given_name": "Amna", "family_name": "Kashgari", "ORCID": null, "country": null }, { "author_id": 277120, "given_name": "John-Paul", "family_name": "Kilday", "ORCID": null, "country": null }, { "author_id": 277121, "given_name": "Alyssa", "family_name": "Kirsch", "ORCID": null, "country": null }, { "author_id": 277122, "given_name": "Manoelle", "family_name": "Kossorotoff", "ORCID": null, "country": null }, { "author_id": 277123, "given_name": "Anant", "family_name": "Krishnan", "ORCID": null, "country": null }, { "author_id": 277124, "given_name": "Shilpa", "family_name": "Kulkarni", "ORCID": null, "country": null }, { "author_id": 277125, "given_name": "Marianne", "family_name": "Leruez-Vill", "ORCID": null, "country": null }, { "author_id": 277126, "given_name": "Fabrice", "family_name": "Lesage", "ORCID": null, "country": null }, { "author_id": 277127, "given_name": "Raphaël", "family_name": "Levy", "ORCID": null, "country": null }, { "author_id": 161408, "given_name": "Yi", "family_name": "Li", "ORCID": "http://orcid.org/0000-0003-0520-9068", "country": null }, { "author_id": 277128, "given_name": "Carol Cavalcante de Vasconcelos", "family_name": "Lima", "ORCID": null, "country": null }, { "author_id": 277129, "given_name": "Lokesh", "family_name": "Lingappa", "ORCID": null, "country": null }, { "author_id": 277130, "given_name": "Ulrike", "family_name": "Löbel", "ORCID": null, "country": null }, { "author_id": 277131, "given_name": "Roberto", "family_name": "Lopez-Alberola", "ORCID": null, "country": null }, { "author_id": 212004, "given_name": "Leandro Tavares", "family_name": "Lucato", "ORCID": "http://orcid.org/0000-0001-9181-5245", "country": null }, { "author_id": 277132, "given_name": "Daniela Duarte", "family_name": "Moreira", "ORCID": null, "country": null }, { "author_id": 277133, "given_name": "Jonathan G.", "family_name": "Murnick", "ORCID": null, "country": null }, { "author_id": 277134, "given_name": "Sarah", "family_name": "Nahmani", "ORCID": null, "country": null }, { "author_id": 277135, "given_name": "Shubra", "family_name": "Pagariya", "ORCID": null, "country": null }, { "author_id": 277136, "given_name": "Julija", "family_name": "Pavaine", "ORCID": null, "country": null }, { "author_id": 277137, "given_name": "Bryan", "family_name": "Philbrook", "ORCID": null, "country": null }, { "author_id": 277138, "given_name": "Ana Cláudia", "family_name": "Piovesan", "ORCID": null, "country": null }, { "author_id": 277139, "given_name": "Kelsey E.", "family_name": "Poisson", "ORCID": null, "country": null }, { "author_id": 277140, "given_name": "Nihaal", "family_name": "Reddy", "ORCID": null, "country": null }, { "author_id": 277141, "given_name": "Phil", "family_name": "Riley", "ORCID": null, "country": null }, { "author_id": 277142, "given_name": "Andrea", "family_name": "Romsauerova", "ORCID": null, "country": null }, { "author_id": 277143, "given_name": "Charlies-Joris", "family_name": "Roux", "ORCID": null, "country": null }, { "author_id": 274251, "given_name": "Carlos", "family_name": "Rugilo", "ORCID": null, "country": null }, { "author_id": 277144, "given_name": "Gaurav", "family_name": "Saigal", "ORCID": null, "country": null }, { "author_id": 277145, "given_name": "Gabriel Lucca de Oliveira", "family_name": "Salvador", "ORCID": null, "country": null }, { "author_id": 277146, "given_name": "David", "family_name": "Seidenwurm", "ORCID": null, "country": null }, { "author_id": 277148, "given_name": "Isabelle", "family_name": "Sermet-Gaudelus", "ORCID": null, "country": null }, { "author_id": 277149, "given_name": "Jai", "family_name": "Sidpra", "ORCID": null, "country": null }, { "author_id": 277150, "given_name": "Sniya Valsa", "family_name": "Sudhakar", "ORCID": null, "country": null }, { "author_id": 277152, "given_name": "María Sol", "family_name": "Toronchik", "ORCID": null, "country": null }, { "author_id": 277154, "given_name": "Gilbert", "family_name": "Vézina", "ORCID": null, "country": null } ], "relevant": false, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Neuroimaging manifestations", "children", "SARS-CoV-2 infection", "a multinational, multicentre collaborative study" ], "doi": "10.1016/S2352-4642(20)30362-X", "access": "open", "takeaways": " The most common imaging patterns were postinfectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients), myelitis (eight patients), and neural enhancement (13 patients) Cranial nerve enhancement could occur in the absence of corresponding neurological symptoms . Cerebrovascular complications in children were less common than in adults .", "categories": [] }, { "article_id": 314, "title": "Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial", "summary": "<h2>Summary</h2><h3>Background</h3><p>There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort.</p><h3>Methods</h3><p>SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18–65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5–6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29).</p><h3>Findings</h3><p>From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15–27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81–2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (<1%) person died in the MD1003 group and there were no deaths in the placebo group. Despite use of mitigation strategies, MD1003 led to inaccurate laboratory results for tests using biotinylated antibodies.</p><h3>Interpretation</h3><p>This study showed that MD1003 did not significantly improve disability or walking speed in patients with progressive multiple sclerosis and thus, in addition to the potential of MD1003 for deleterious health consequences from interference of laboratory tests, MD1003 cannot be recommended for treatment of progressive multiple sclerosis.</p><h3>Funding</h3><p>MedDay Pharmaceuticals.</p>", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30347-1/fulltext", "published_date": "2020-10-22T23:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 248491, "given_name": "Bruce A C", "family_name": "Cree", "ORCID": null, "country": null }, { "author_id": 240824, "given_name": "Gary", "family_name": "Cutter", "ORCID": null, "country": null }, { "author_id": 241104, "given_name": "Jerry S", "family_name": "Wolinsky", "ORCID": null, "country": null }, { "author_id": 153178, "given_name": "Mark S", "family_name": "Freedman", "ORCID": "http://orcid.org/0000-0003-1255-9701", "country": "CA" }, { "author_id": 149342, "given_name": "Giancarlo", "family_name": "Comi", "ORCID": "http://orcid.org/0000-0002-6989-1054", "country": null }, { "author_id": 143429, "given_name": "Gavin", "family_name": "Giovannoni", "ORCID": "http://orcid.org/0000-0001-9995-1700", "country": null }, { "author_id": 181330, "given_name": "Hans-Peter", "family_name": "Hartung", "ORCID": "http://orcid.org/0000-0002-0614-6989", "country": null }, { "author_id": 244012, "given_name": "Douglas", "family_name": "Arnold", "ORCID": null, "country": null }, { "author_id": 154809, "given_name": "Jens", "family_name": "Kuhle", "ORCID": "http://orcid.org/0000-0002-6963-8892", "country": "CH" }, { "author_id": 172098, "given_name": "Valerie", "family_name": "Block", "ORCID": "http://orcid.org/0000-0001-6199-5484", "country": "US" }, { "author_id": 247955, "given_name": "Frederick E", "family_name": "Munschauer", "ORCID": null, "country": null }, { "author_id": 248495, "given_name": "Frédéric", "family_name": "Sedel", "ORCID": null, "country": null }, { "author_id": 172546, "given_name": "Fred D", "family_name": "Lublin", "ORCID": "http://orcid.org/0000-0001-5722-0475", "country": null }, { "author_id": 248496, "given_name": "Stephen", "family_name": "Reingold", "ORCID": null, "country": null }, { "author_id": 183403, "given_name": "Pierre", "family_name": "Duquette", "ORCID": "http://orcid.org/0000-0001-7231-1754", "country": null }, { "author_id": 152403, "given_name": "Tobias", "family_name": "Derfuss", "ORCID": "http://orcid.org/0000-0001-8431-8769", "country": null }, { "author_id": 241329, "given_name": "Franz", "family_name": "Fazekas", "ORCID": null, "country": null }, { "author_id": 149329, "given_name": "Maria Pia", "family_name": "Sormani", "ORCID": "http://orcid.org/0000-0001-6892-104X", "country": null }, { "author_id": 248497, "given_name": "Robert P.", "family_name": "Lisak", "ORCID": null, "country": null }, { "author_id": 159536, "given_name": "Jennifer", "family_name": "Graves", "ORCID": "http://orcid.org/0000-0003-1539-1940", "country": null }, { "author_id": 240958, "given_name": "Stephen", "family_name": "Krieger", "ORCID": null, "country": null }, { "author_id": 248498, "given_name": "Rana K.", "family_name": "Zabad", "ORCID": null, "country": null }, { "author_id": 246981, "given_name": "Scott", "family_name": "Newsome", "ORCID": null, "country": null }, { "author_id": 248499, "given_name": "Joshua", "family_name": "Barton", "ORCID": null, "country": null }, { "author_id": 248500, "given_name": "Richard", "family_name": "MacDonell", "ORCID": null, "country": null }, { "author_id": 248501, "given_name": "Mark", "family_name": "Marriott", "ORCID": null, "country": null }, { "author_id": 248502, "given_name": "Nina", "family_name": "De Klippel", "ORCID": null, "country": null }, { "author_id": 231369, "given_name": "Guy", "family_name": "Laureys", "ORCID": "http://orcid.org/0000-0002-1708-4373", "country": null }, { "author_id": 184068, "given_name": "Barbara", "family_name": "Willekens", "ORCID": "http://orcid.org/0000-0002-5212-8837", "country": "BE" }, { "author_id": 245696, "given_name": "Virginia", "family_name": "Devonshire", "ORCID": null, "country": null }, { "author_id": 248503, "given_name": "Mark", "family_name": "Freedman", "ORCID": null, "country": null }, { "author_id": 248504, "given_name": "J Marc", "family_name": "Girard", "ORCID": null, "country": null }, { "author_id": 248506, "given_name": "Paul", "family_name": "Giacomini", "ORCID": null, "country": null }, { "author_id": 248508, "given_name": "Roger", "family_name": "McKelvey", "ORCID": null, "country": null }, { "author_id": 245799, "given_name": "Daniel", "family_name": "Selchen", "ORCID": null, "country": null }, { "author_id": 241547, "given_name": "Galina", "family_name": "Vorobeychik", "ORCID": null, "country": null }, { "author_id": 248511, "given_name": "Ludivine", "family_name": "Witkowski", "ORCID": null, "country": null }, { "author_id": 248513, "given_name": "Radek", "family_name": "Ampapa", "ORCID": null, "country": null }, { "author_id": 150336, "given_name": "Jana Lizrova", "family_name": "Preiningerova", "ORCID": "http://orcid.org/0000-0003-0337-3462", "country": "CZ" }, { "author_id": 248516, "given_name": "Eva", "family_name": "Meluzinova", "ORCID": null, "country": null }, { "author_id": 248517, "given_name": "Radomir", "family_name": "Talab", "ORCID": null, "country": null }, { "author_id": 248518, "given_name": "Marta", "family_name": "Vachova", "ORCID": null, "country": null }, { "author_id": 149649, "given_name": "Orhan", "family_name": "Aktas", "ORCID": "http://orcid.org/0000-0002-2020-9210", "country": null }, { "author_id": 248520, "given_name": "Mathias", "family_name": "Buttmann", "ORCID": null, "country": null }, { "author_id": 248521, "given_name": "Elias-Hamp", "family_name": "Birte", "ORCID": null, "country": null }, { "author_id": 199738, "given_name": "Tania", "family_name": "Kümpfel", "ORCID": "http://orcid.org/0000-0001-7509-5268", "country": null }, { "author_id": 248522, "given_name": "Paul", "family_name": "Friedemann", "ORCID": null, "country": null }, { "author_id": 160585, "given_name": "Daniela", "family_name": "Rau", "ORCID": "http://orcid.org/0000-0002-0288-3762", "country": null }, { "author_id": 248523, "given_name": "Gerd", "family_name": "Reifschneider", "ORCID": null, "country": null }, { "author_id": 248524, "given_name": "Piotr", "family_name": "Sokolowski", "ORCID": null, "country": null }, { "author_id": 157222, "given_name": "Hayrettin", "family_name": "Tumani", "ORCID": "http://orcid.org/0000-0002-1647-6201", "country": null }, { "author_id": 248525, "given_name": "Maria", "family_name": "Satori", "ORCID": null, "country": null }, { "author_id": 150619, "given_name": "Carlo", "family_name": "Pozzilli", "ORCID": "http://orcid.org/0000-0002-6360-4798", "country": null }, { "author_id": 248526, "given_name": "Agata", "family_name": "Klosek", "ORCID": null, "country": null }, { "author_id": 248527, "given_name": "Jozef", "family_name": "Koscielniak", "ORCID": null, "country": null }, { "author_id": 248528, "given_name": "Fryze", "family_name": "Waldemar", "ORCID": null, "country": null }, { "author_id": 248529, "given_name": "Malgorzata", "family_name": "Zajda", "ORCID": null, "country": null }, { "author_id": 248530, "given_name": "Rafael Arroyo", "family_name": "Gonzalez", "ORCID": null, "country": null }, { "author_id": 248532, "given_name": "Victoria Fernandez", "family_name": "Sanchez", "ORCID": null, "country": null }, { "author_id": 248533, "given_name": "Celia Oreja", "family_name": "Guevara", "ORCID": null, "country": null }, { "author_id": 248534, "given_name": "Jose Enrique Martinez", "family_name": "Rodriguez", "ORCID": null, "country": null }, { "author_id": 154801, "given_name": "Xavier", "family_name": "Montalban", "ORCID": "http://orcid.org/0000-0002-0098-9918", "country": "ES" }, { "author_id": 248535, "given_name": "Lluis", "family_name": "Ramio-Torrenta", "ORCID": null, "country": null }, { "author_id": 218790, "given_name": "Lou", "family_name": "Brundin", "ORCID": "http://orcid.org/0000-0003-4408-7817", "country": null }, { "author_id": 173692, "given_name": "Jan", "family_name": "Lycke", "ORCID": "http://orcid.org/0000-0002-7891-8466", "country": null }, { "author_id": 173491, "given_name": "Murat", "family_name": "Terzi", "ORCID": "http://orcid.org/0000-0002-3586-9115", "country": null }, { "author_id": 248539, "given_name": "Joe", "family_name": "Guadagno", "ORCID": null, "country": null }, { "author_id": 242055, "given_name": "Don", "family_name": "Mahad", "ORCID": null, "country": null }, { "author_id": 248542, "given_name": "Adrian", "family_name": "Pace", "ORCID": null, "country": null }, { "author_id": 248543, "given_name": "Klaus", "family_name": "Schmierer", "ORCID": null, "country": null }, { "author_id": 150342, "given_name": "Ahmed", "family_name": "Toosy", "ORCID": "http://orcid.org/0000-0002-4441-3750", "country": null }, { "author_id": 248547, "given_name": "Stewart", "family_name": "Webb", "ORCID": null, "country": null }, { "author_id": 248549, "given_name": "Mark", "family_name": "Agius", "ORCID": null, "country": null }, { "author_id": 247785, "given_name": "Lilyana", "family_name": "Amezcua", "ORCID": null, "country": null }, { "author_id": 248552, "given_name": "Michelle", "family_name": "Apperson", "ORCID": null, "country": null }, { "author_id": 248553, "given_name": "Bridget", "family_name": "Bagert", "ORCID": null, "country": null }, { "author_id": 248554, "given_name": "Daniel", "family_name": "Bandari", "ORCID": null, "country": null }, { "author_id": 191145, "given_name": "Evanthia", "family_name": "Bernitsas", "ORCID": "http://orcid.org/0000-0001-9382-1008", "country": null }, { "author_id": 248555, "given_name": "Jonathan", "family_name": "Calkwood", "ORCID": null, "country": null }, { "author_id": 248556, "given_name": "Jonathan", "family_name": "Carter", "ORCID": null, "country": null }, { "author_id": 248557, "given_name": "Bruce", "family_name": "Cohen", "ORCID": null, "country": null }, { "author_id": 248558, "given_name": "Devon", "family_name": "Conway", "ORCID": null, "country": null }, { "author_id": 248559, "given_name": "Joanna", "family_name": "Cooper", "ORCID": null, "country": null }, { "author_id": 248560, "given_name": "John", "family_name": "Corboy", "ORCID": null, "country": null }, { "author_id": 240686, "given_name": "Patricia", "family_name": "Coyle", "ORCID": null, "country": null }, { "author_id": 248561, "given_name": "Bruce", "family_name": "Cree", "ORCID": null, "country": null }, { "author_id": 248562, "given_name": "Mitchel", "family_name": "Freedman", "ORCID": null, "country": null }, { "author_id": 248563, "given_name": "Corey", "family_name": "Ford", "ORCID": null, "country": null }, { "author_id": 248564, "given_name": "Edward", "family_name": "Fox", "ORCID": null, "country": null }, { "author_id": 248565, "given_name": "Myla", "family_name": "Goldman", "ORCID": null, "country": null }, { "author_id": 244431, "given_name": "Benjamin", "family_name": "Greenberg", "ORCID": null, "country": null }, { "author_id": 248566, "given_name": "Mariko", "family_name": "Kita", "ORCID": null, "country": null }, { "author_id": 248567, "given_name": "Thomas", "family_name": "Leist", "ORCID": null, "country": null }, { "author_id": 236905, "given_name": "Sharon", "family_name": "Lynch", "ORCID": null, "country": null }, { "author_id": 241112, "given_name": "Aaron", "family_name": "Miller", "ORCID": null, "country": null }, { "author_id": 248568, "given_name": "Harold", "family_name": "Moses", "ORCID": null, "country": null }, { "author_id": 185814, "given_name": "Robert", "family_name": "Naismith", "ORCID": "http://orcid.org/0000-0003-0520-4283", "country": null }, { "author_id": 248571, "given_name": "Mary Ann", "family_name": "Picone", "ORCID": null, "country": null }, { "author_id": 248573, "given_name": "Bhatia", "family_name": "Perminder", "ORCID": null, "country": null }, { "author_id": 240594, "given_name": "Alexander", "family_name": "Rae-Grant", "ORCID": null, "country": null }, { "author_id": 208597, "given_name": "Kottil", "family_name": "Rammohan", "ORCID": "http://orcid.org/0000-0003-2467-4280", "country": null }, { "author_id": 248575, "given_name": "Anthony", "family_name": "Reder", "ORCID": null, "country": null }, { "author_id": 248576, "given_name": "Claire", "family_name": "Riley", "ORCID": null, "country": null }, { "author_id": 248577, "given_name": "Derrick", "family_name": "Robertson", "ORCID": null, "country": null }, { "author_id": 248578, "given_name": "Vernon", "family_name": "Rowe", "ORCID": null, "country": null }, { "author_id": 172340, "given_name": "Shiv", "family_name": "Saidha", "ORCID": "http://orcid.org/0000-0001-6387-0714", "country": null }, { "author_id": 248579, "given_name": "Lawrence", "family_name": "Samkoff", "ORCID": null, "country": null }, { "author_id": 248580, "given_name": "Christopher", "family_name": "Severson", "ORCID": null, "country": null }, { "author_id": 248581, "given_name": "Kyle", "family_name": "Smoot", "ORCID": null, "country": null }, { "author_id": 248582, "given_name": "Sharon", "family_name": "Stoll", "ORCID": null, "country": null }, { "author_id": 248583, "given_name": "Randall", "family_name": "Trudell", "ORCID": null, "country": null }, { "author_id": 152480, "given_name": "Bianca", "family_name": "Weinstock-Guttman", "ORCID": "http://orcid.org/0000-0001-6732-151X", "country": null }, { "author_id": 248584, "given_name": "Sanjay", "family_name": "Yathiraj", "ORCID": null, "country": null }, { "author_id": 326667, "given_name": "Guillermo Izquierdo", "family_name": "Ayuso", "ORCID": "http://orcid.org/0000-0002-6340-5609", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Safety", "efficacy", "MD1003", "(high-dose biotin", "patients", "progressive multiple sclerosis", "SPI2", "phase", "3 trial" ], "doi": "10.1016/S1474-4422(20)30347-1", "access": "open", "takeaways": " MS-SPI randomised, double-blind, placebo-controlled study found MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis . The study was designed to assess safety and efficacy of biotin in progressive forms of multiple sclerosis in a larger, more representative patient cohort .", "categories": [] }, { "article_id": 318, "title": "Cognition in multiple sclerosis: Charcot was right", "summary": "Charcot's early descriptions of patients with multiple sclerosis noted “enfeeblement of memory” and “concepts formed slowly,” along with the classic triad of nystagmus, intention tremor, and ataxic dysarthria. 1 Charcot was trained in psychiatry and neurology, but for decades neither discipline took note of his psychological observations. Psychiatrists in the 1920s used interviews to probe mental status in people with multiple sclerosis, but estimates of the frequency of cognitive impairment were unreliable, ranging from two to 72%. 2", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30306-9/fulltext", "published_date": "2020-09-30T23:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 242082, "given_name": "Ralph H B", "family_name": "Benedict", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "multiple sclerosis", "Charcot" ], "doi": "10.1016/S1474-4422(20)30306-9", "access": "restricted", "takeaways": " Charcot's early descriptions of patients with multiple sclerosis noted “enfeeblement of memory” and “concepts formed slowly” along with the classic triad", "categories": [] }, { "article_id": 325, "title": "hESC-derived immune suppressive dendritic cells induce immune tolerance of parental hESC-derived allografts", "summary": "Background With their inherent capability of unlimited self-renewal and unique potential to differentiate into functional cells of the three germ layers, human embryonic stem cells (hESCs) hold great potential in regenerative medicine. A major challenge in the application of hESC-based cell therapy is the allogeneic immune rejection of hESC-derived allografts. Methods We derived dendritic cell-like cells (DCLs) from wild type and CTLA4-Ig/PD-L1 knock-in hESCs, denoted WT DCLs and CP DCLs. The expression of DC-related genes and surface molecules was evaluated, as well as their DCL capacity to stimulate allogeneic T cells and induce regulatory T (Treg) cells in vitro. Using an immune system humanized mouse model, we investigated whether the adoptive transfer of CP DCLs can induce long-term immune tolerance of parental hESC-derived smooth muscle and cardiomyocyte allografts. Findings CP DCLs can maintain immune suppressive properties after robust inflammatory stimulation and induce Treg cells. While CP DCLs survive transiently in vivo, they induce long-term immune tolerance of parental hESC-derived allografts. Interpretation This strategy does not cause systemic immune suppression but induces immune tolerance specific for DCL-specific HLAs, and thus it presents a safe and effective approach to induce immune tolerance of allografts derived from any clinically approved hESC line. Funding NSFC, leading talents of Guangdong Province Program (No. 00201516), Key R&D Program of Guangdong Province (2019B020235003), Science and Technology Innovation Committee of Shenzhen Municipality (JCYJ20180504170301309), National High-tech R&D Program (863 Program No. 2015AA020310), Shenzhen “Sanming” Project of Medicine (SZSM201602102), Development and Reform Commission of Shenzhen Municipality (S2016004730009), CIRM (DISC2–10559).", "link": "https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(20)30496-5/fulltext", "published_date": "2020-11-23T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "eBioMedicine", "authors": [ { "author_id": 294922, "given_name": "Dilyana", "family_name": "Todorova", "ORCID": null, "country": null }, { "author_id": 258940, "given_name": "Yue", "family_name": "Zhang", "ORCID": null, "country": null }, { "author_id": 294924, "given_name": "Qu", "family_name": "Chen", "ORCID": null, "country": null }, { "author_id": 294925, "given_name": "Jingfeng", "family_name": "Liu", "ORCID": null, "country": null }, { "author_id": 294926, "given_name": "Jingjin", "family_name": "He", "ORCID": null, "country": null }, { "author_id": 294928, "given_name": "Xuemei", "family_name": "Fu", "ORCID": null, "country": null }, { "author_id": 294929, "given_name": "Yang", "family_name": "Xu", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "hESC-derived immune suppressive dendritic cells", "immune tolerance", "parental hESC-derived allografts" ], "doi": "10.1016/j.ebiom.2020.103120", "access": "open", "takeaways": " Human embryonic stem cells (hESCs) hold great potential in regenerative medicine . A major challenge in the application of hESC-based cell therapy is the allogeneic immune rejection of allografts . Using an immune system humanized mouse model, we investigated whether adoptive transfer of CP DCLs can induce long-term immune tolerance . This strategy does not cause systemic immune suppression but induces immune tolerance specific for DCL-specific HLAs .", "categories": [] }, { "article_id": 323, "title": "Remyelination in multiple sclerosis: from basic science to clinical translation", "summary": "<h2>Summary</h2><p>The treatment of multiple sclerosis has been transformed by the successful development of immunotherapies that efficiently reduce disease activity and related clinical relapses during the relapsing-remitting phase of the disease. However, the prevention of disability progression, which is due to axonal and neuronal damage and loss, has yet to be achieved and is therapeutically challenging, particularly during the progressive phase of the disease. One strategy to counteract neurodegeneration is to promote neuroprotection by enhancing myelin regeneration, hence restoring nerve conduction and metabolic support to the axon. Animal studies have provided targets for interventions to improve brain and spinal cord remyelination, paving the way for the translation of this research to humans. From these initial and promising forays, further problems have emerged, including questions on how best to design these clinical trials and appropriately measure the outcomes. Solving these problems will need additional work before efficacious pro-remyelination therapies will be ready for people with multiple sclerosis, but there is a real sense of hope that researchers are getting closer to a successful therapy.</p>", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30140-X/fulltext", "published_date": "2020-07-31T23:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 204624, "given_name": "Catherine", "family_name": "Lubetzki", "ORCID": "http://orcid.org/0000-0001-7164-3175", "country": null }, { "author_id": 150354, "given_name": "Anna", "family_name": "Williams", "ORCID": "http://orcid.org/0000-0002-6329-382X", "country": "GB" }, { "author_id": 146915, "given_name": "Christine", "family_name": "Stadelmann", "ORCID": "http://orcid.org/0000-0003-1766-5458", "country": null }, { "author_id": 149339, "given_name": "Bruno", "family_name": "Stankoff", "ORCID": "http://orcid.org/0000-0002-9631-4674", "country": null }, { "author_id": 329026, "given_name": "Bernard", "family_name": "Zalc", "ORCID": "http://orcid.org/0000-0001-5484-2359", "country": null } ], "relevant": true, "ml_prediction_gnb": true, "ml_prediction_lr": false, "ml_prediction_lsvc": true, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Remyelination", "multiple sclerosis", "basic science", "clinical translation" ], "doi": "10.1016/S1474-4422(20)30140-X", "access": "open", "takeaways": " The prevention of disability progression, which is due to axonal and neuronal damage and loss, has yet to be achieved . One strategy to counteract neurodegeneration is to promote neuroprotection by enhancing myelin regeneration . Animal studies have provided targets for interventions to improve brain and spinal cord remyelination .", "categories": [] }, { "article_id": 311, "title": "Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial", "summary": "<h2>Summary</h2><h3>Background</h3><p>Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis; however, the evidence supporting their efficacy is sparse and conflicting. Our goal was to compare the efficacy of these three medications with each other and placebo in patients with multiple sclerosis fatigue.</p><h3>Methods</h3><p>In this randomised, placebo-controlled, four-sequence, four-period, crossover, double-blind trial, patients with multiple sclerosis who reported fatigue and had a Modified Fatigue Impact Scale (MFIS) score of more than 33 were recruited at two academic multiple sclerosis centres in the USA. Participants received oral amantadine (up to 100 mg twice daily), modafinil (up to 100 mg twice daily), methylphenidate (up to 10 mg twice daily), or placebo, each given for up to 6 weeks. All patients were intended to receive all four study medications, in turn, in one of four different sequences with 2-week washout periods between medications. A biostatistician prepared a concealed allocation schedule, stratified by site, randomly assigning a sequence of medications in approximately a 1:1:1:1 ratio, in blocks of eight, to a consecutive series of numbers. The statistician and pharmacists had no role in assessing the participants or collecting data, and the participants, caregivers, and assessors were masked to allocation. The primary outcome measure was the MFIS measured while taking the highest tolerated dose at week 5 of each medication period, analysed by use of a linear mixed-effect regression model. This trial is registered with ClinicalTrials.gov, NCT03185065 and is closed.</p><h3>Findings</h3><p>Between Oct 4, 2017, and Feb 27, 2019, of 169 patients screened, 141 patients were enrolled and randomly assigned to one of four medication administration sequences: 35 (25%) patients to the amantadine, placebo, modafinil, and methylphenidate sequence; 34 (24%) patients to the placebo, methylphenidate, amantadine, and modafinil sequence; 35 (25%) patients to the modafinil, amantadine, methylphenidate, and placebo sequence; and 37 (26%) patients to the methylphenidate, modafinil, placebo, and amantadine sequence. Data from 136 participants were available for the intention-to-treat analysis of the primary outcome. The estimated mean values of MFIS total scores at baseline and the maximal tolerated dose were as follows: 51·3 (95% CI 49·0–53·6) at baseline, 40·6 (38·2–43·1) with placebo, 41·3 (38·8–43·7) with amantadine, 39·0 (36·6–41·4) with modafinil, and 38·6 (36·2–41·0) with methylphenidate (p=0·20 for the overall medication effect in the linear mixed-effect regression model). As compared with placebo (38 [31%] of 124 patients), higher proportions of participants reported adverse events while taking amantadine (49 [39%] of 127 patients), modafinil (50 [40%] of 125 patients), and methylphenidate (51 [40%] of 129 patients). Three serious adverse events occurred during the study (pulmonary embolism and myocarditis while taking amantadine, and a multiple sclerosis exacerbation requiring hospital admission while taking modafinil).</p><h3>Interpretation</h3><p>Amantadine, modafinil, and methylphenidate were not superior to placebo in improving multiple sclerosis fatigue and caused more frequent adverse events. The results of this study do not support an indiscriminate use of amantadine, modafinil, or methylphenidate for the treatment of fatigue in multiple sclerosis.</p><h3>Funding</h3><p>Patient-Centered Outcomes Research Institute.</p>", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30354-9/fulltext", "published_date": "2020-11-23T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 171980, "given_name": "Bardia", "family_name": "Nourbakhsh", "ORCID": "http://orcid.org/0000-0002-6617-2003", "country": null }, { "author_id": 242212, "given_name": "Nisha", "family_name": "Revirajan", "ORCID": null, "country": null }, { "author_id": 256111, "given_name": "Bridget", "family_name": "Morris", "ORCID": null, "country": null }, { "author_id": 152815, "given_name": "Christian", "family_name": "Cordano", "ORCID": "http://orcid.org/0000-0002-1413-0442", "country": "IT" }, { "author_id": 256112, "given_name": "Jennifer", "family_name": "Creasman", "ORCID": null, "country": null }, { "author_id": 242213, "given_name": "Michael", "family_name": "Manguinao", "ORCID": null, "country": null }, { "author_id": 195175, "given_name": "Kristen", "family_name": "Krysko", "ORCID": "http://orcid.org/0000-0003-0090-597X", "country": null }, { "author_id": 318694, "given_name": "Alice", "family_name": "Rutatangwa", "ORCID": "http://orcid.org/0000-0003-0843-7947", "country": null }, { "author_id": 256113, "given_name": "Caroline", "family_name": "Auvray", "ORCID": null, "country": null }, { "author_id": 193995, "given_name": "Salman", "family_name": "Aljarallah", "ORCID": "http://orcid.org/0000-0003-0138-7924", "country": "SA" }, { "author_id": 256114, "given_name": "Chengshi", "family_name": "Jin", "ORCID": null, "country": null }, { "author_id": 255942, "given_name": "Ellen", "family_name": "Mowry", "ORCID": null, "country": null }, { "author_id": 256115, "given_name": "Charles", "family_name": "McCulloch", "ORCID": null, "country": null }, { "author_id": 151879, "given_name": "Emmanuelle", "family_name": "Waubant", "ORCID": "http://orcid.org/0000-0001-5188-0157", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Safety", "efficacy", "amantadine", "modafinil", "fatigue", "multiple sclerosis", "a randomised, placebo-controlled, crossover, double-blind trial" ], "doi": "10.1016/S1474-4422(20)30354-9", "access": "open", "takeaways": " Amantadine, modafinil, and methylphenidate were not superior to placebo in improving multiple sclerosis fatigue and caused more frequent adverse events . The results of this study do not support an indiscriminate use of these medications for the treatment of multiple sclerosis .", "categories": [] }, { "article_id": 312, "title": "Are drugs for multiple sclerosis fatigue just placebos?", "summary": "About 80% of multiple sclerosis patients have fatigue, which is commonly their most troublesome problem. 1 , 2 Fatigue is often disabling, affecting employment and other activities. Unfortunately, multiple sclerosis fatigue is difficult to treat, frustrating our patients and ourselves. Treatments include exercise, energy conservation, and cognitive behavioural counselling. As physicians, we are inclined to prescribe medications for our patients with multiple sclerosis who have fatigue, and our patients often report that a medication that we have prescribed has improved their fatigue. However, there is conflicting evidence about whether drugs commonly prescribed for multiple sclerosis fatigue are effective. 3 , 4 Are these medications truly effective or are they having a placebo effect?", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30415-4/fulltext", "published_date": "2020-11-23T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 154538, "given_name": "Dennis", "family_name": "Bourdette", "ORCID": "http://orcid.org/0000-0002-1312-8615", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "drugs", "multiple sclerosis fatigue", "just placebos" ], "doi": "10.1016/S1474-4422(20)30415-4", "access": "restricted", "takeaways": " 80% of multiple sclerosis patients have fatigue, which is commonly their most troublesome problem . Fatigue is often disabling, affecting employment and other activities . Treatments include exercise, energy conservation, and cognitive behavioural counselling .", "categories": [] }, { "article_id": 309, "title": "Multiple sclerosis in 2020: un bon cru", "summary": "The landscape of multiple sclerosis is changing, with new insights on prognosis, the emergence of artificial intelligence in brain imaging, technological advances challenging knowledge on disease pathogenesis, and the identification of novel therapeutic pathways. However, 2020 will certainly be remembered for the spread of the COVID-19 pandemic. In this context, the possibility of an increased susceptibility to severe COVID-19 in patients with multiple sclerosis has rapidly become an important question. Higher age, an Expanded Disability Status Scale score of 6 or more, and obesity were identified as independent risk factors for severe COVID-19 in a French multicentre observational cohort.1 Whereas in this study, which included 347 patients, there was no significant association between disease-modifying treatment exposure and COVID-19 severity, some evidence is now emerging that therapies targeting CD20 might be linked to an increased risk of severe COVID-19, and several studies aiming to establish whether this is the case are ongoing. How to manage individuals with radiologically isolated syndrome—people with brain MRI scans compatible with CNS inflammation but without neurological symptoms—remains challenging because the long-term outcome after this diagnosis is unknown. The multicentre Radiologically Isolated Syndrome Consortium study,2 the largest and longest study to date, included 277 individuals with radiologically isolated syndrome. The cumulative probability of a clinical event at 10 years was 51·2%. Consistent with previous publications, young age and spinal cord lesions were identified as independent predictors of a first clinical event. The novelty here is the identification of two additional risk factors—the presence of oligoclonal bands or elevated IgG index in the CSF and infratentorial lesions—with a stepwise increase of risk associated with the number of factors (probability ranging from 29% for individuals with at least one risk factor to 87% for those with four risk factors). Nevertheless, in the absence of results from ongoing trials of potential disease-modifying drugs (TERIS [NCT03122652] and ARISE [NCT02739542]), there is no recommendation to treat individuals with radiologically isolated syndrome. Artificial intelligence has opened new avenues for medical imaging in general. In multiple sclerosis, one example is a deep learning approach applying convolutional neural networks,4 evaluating the possibility of predicting brain lesion activity without the need for contrast injection. In this study, conventional MRI data from 519 patients with a total of 1390 enhancing lesions were used to train and test network performance. Participants with enhancing lesions were classified with 70% accuracy. Similarly, a method proposed by Wei and colleages4 could offer an alternative to PET scanning to predict myelin content changes by using multisequence quantitative MRI. Myelin imaging with 11C-PIB PET allows quantification of myelin content changes in vivo, but is invasive, with injection of a radioactive tracer, and is poorly suited to multicentre studies. The deep learning approach used by Wei and colleagues4 allowed generation of synthetic images predicting myelin content changes in a longitudinal analysis of patients with multiple sclerosis. By providing MRI-based algorithms, deep learning methods are likely to modify, in the near future, the management of patients with multiple sclerosis, as well as the design of therapeutic studies. With regard to disease pathogenesis, single-cell RNA-sequencing methods have revealed heterogeneity in oligodendroglia, neurons, and microglia in healthy and multiple sclerosis tissue. In a single-cell genetic and epigenetic study, Wheeler and colleagues5 investigated the heterogeneity of astrocytes in multiple sclerosis tissue and in experimental autoimmune encephalomyelitis (a rodent model of multiple sclerosis); they identified a subpopulation of astrocytes characterised by decreased expression of the antioxidant transcription factor NRF2 and increased expression of the transcription factor MAFG, leading to repression of anti-oxidant and anti-inflammatory transcriptional programmes. Such pro-inflammatory astrocytes are detected within active white matter lesions in patients with multiple sclerosis. These results, which identify how astrocytes might contribute to inflammation and tissue damage, open perspectives for therapeutic candidates targeting neurotoxic astrocytic activity. Promoting neuroprotection in multiple sclerosis is a major challenge because irreversible disability is highly correlated with the accumulation of neuronal damage. Several trials of pro-remyelinating candidates are ongoing.6 In this context, negative results from the AFFINITY trial of the effect of opicinumab on disability in patients with relapsing multiple sclerosis were released, ending the development of the anti-LINGO-1 strategy. Bexarotene to promote remyelination has also been trialled in patients with relapsing multiple sclerosis (EudraCT 2014-003145-99) and, although the primary efficacy outcome was reported to be negative and the drug was poorly tolerated, secondary outcomes suggest that it might promote myelin repair.7 With regard to direct neuroprotection, the negative results of the MS-SMART study were disappointing.8 This phase 2b, multi-arm, parallel-group, double-blind, randomised placebo-controlled trial aimed to evaluate three neuroprotective drugs (amiloride, fluoxetine, and riluzole) selected from searches of research in animal models and clinical trials. In the primary analysis of 393 patients with secondary progressive multiple sclerosis, none of the therapeutic groups showed an improvement in the primary outcome (volumetric MRI percentage brain volume change) from baseline to 96 weeks compared with placebo. However, despite this negative result, the study convincingly showed the value and feasibility of a multi-arm phase 2 trial designed to inform a go or no-go decision for phase 3 trials targeting neuroprotection. Finally, the results of a trial of masitinib (NCT01433497) to target innate immunity suggested a positive effect of the drug versus placebo on disability in patients with progressive multiple sclerosis.9 Finally, exciting data on behavioural interventions from animal models are accumulating. In a study published earlier this year,10 live imaging methods were used to follow oligodendrocytes and individual myelin sheaths in murine demyelinated motor cortex to assess the effect of learning a motor task on remyelination. Training led to increased remyelination by both new and surviving oligodendrocytes—an important result in the debate on the identity of remyelinating cells in the adult CNS. This study not only strengthens the evidence on the role of neuronal activity in myelination, but also provides a convincing demonstration that timely behavioural intervention (after the onset of remyelination) accelerates functional recovery through enhanced remyelination. EM reports grants and personal fees from Biogen, Novartis, and Roche; and personal fees from Merck-Serono, Teva, Sanofi-Genzyme, and Ad Scientiam outside of the submitted work. CL reports grants and personal fees from Biogen; and personal fees from Merck-Serono, Roche, Rewind, and Ipsen outside of the submitted work.", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30441-5/fulltext", "published_date": "2021-01-01T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 143478, "given_name": "Elisabeth", "family_name": "Maillart", "ORCID": "http://orcid.org/0000-0001-7699-0328", "country": null }, { "author_id": 204624, "given_name": "Catherine", "family_name": "Lubetzki", "ORCID": "http://orcid.org/0000-0001-7164-3175", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Multiple sclerosis", "un bon cru" ], "doi": "10.1016/S1474-4422(20)30441-5", "access": "open", "takeaways": "", "categories": [] } ] }