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{ "count": 24866, "next": "http://api.gregory-ms.com/articles/?format=api&page=2457", "previous": "http://api.gregory-ms.com/articles/?format=api&page=2455", "results": [ { "article_id": 308, "title": "Identification of two highly antigenic epitope markers predicting multiple sclerosis in optic neuritis patients", "summary": "<h2>Abstract</h2><h3>Background</h3><p>Optic neuritis (ON) can occur as an isolated episode or will develop to multiple sclerosis (MS) a chronic autoimmune disease. What predicts ON progression to MS remains poorly understood.</p><h3>Methods</h3><p>We characterised the antibody epitope repertoire in three independent clinical cohorts (discovery (<i>n</i> = 62), validation (<i>n</i> = 20) and external cohort (<i>n</i> = 421)) using mimotope variation analysis (MVA), a next generation phage display technology to identify epitopes that associate with prognosis of ON.</p><h3>Findings</h3><p>We observed distinct epitope profiles for ON, MS and the controls, whereas epitope repertoires of sera and CSF were highly similar. Two unique and highly immunogenic epitopes A and B were detected in subjects with ON progressing to MS. These epitopes A and B were strongly associated with herpesviral antigens (VCA p18 of Epstein-Barr virus (EBV); gB of Cytomegalovirus (CMV)). ROC addressed 75% of MS subjects with ON onset correctly (at 75% sensitivity and 74.22% specificity) based on the two-epitope biomarker analysis.</p><h3>Interpretation</h3><p>This is the first report on epitope diagnostics for MS employing the unbiased strategy of MVA for identification of novel immunological features of disease.</p><h3>Funding</h3><p>The Estonian Ministry of Education, The Estonian Research Council (PRG573, PRG805 and PSG691), H2020-MSCA-RISE-2016 (SZTEST), H2020-NMBP-2017 (PANBIORA), Helsinki University Hospital, Mary and Georg C. Ehrnrooth, Finnish Eye, Sigrid Jusélius and Magnus Ehrnrooth Foundations.</p>", "link": "https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00004-9/fulltext", "published_date": "2021-01-23T00:00:00Z", "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": 241548, "given_name": "Helle", "family_name": "Sadam", "ORCID": null, "country": null }, { "author_id": 241549, "given_name": "Arno", "family_name": "Pihlak", "ORCID": null, "country": null }, { "author_id": 241550, "given_name": "Mariliis", "family_name": "Jaago", "ORCID": null, "country": null }, { "author_id": 241551, "given_name": "Nadežda", "family_name": "Pupina", "ORCID": null, "country": null }, { "author_id": 241552, "given_name": "Annika", "family_name": "Rähni", "ORCID": null, "country": null }, { "author_id": 241553, "given_name": "Maarja", "family_name": "Toots", "ORCID": null, "country": null }, { "author_id": 241554, "given_name": "Antti", "family_name": "Vaheri", "ORCID": null, "country": null }, { "author_id": 241555, "given_name": "Janne K.", "family_name": "Nieminen", "ORCID": null, "country": null }, { "author_id": 241556, "given_name": "Mika", "family_name": "Siuko", "ORCID": null, "country": null }, { "author_id": 176474, "given_name": "Pentti J.", "family_name": "Tienari", "ORCID": "http://orcid.org/0000-0001-5686-2900", "country": null }, { "author_id": 241557, "given_name": "Kaia", "family_name": "Palm", "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": [ "Identification", "two highly antigenic epitope markers", "multiple sclerosis", "optic neuritis patients" ], "doi": "10.1016/j.ebiom.2021.103211", "access": "open", "takeaways": " What predicts ON progression to MS remains poorly understood . Two unique and highly immunogenic epitopes A and B were detected in subjects with ON progressing to MS . These epitopes were strongly associated with herpesviral antigens .", "categories": [] }, { "article_id": 305, "title": "Established and novel therapeutic options for autoimmune hepatitis", "summary": "<h2>Summary</h2><p>Autoimmune hepatitis is an immune-mediated disorder characterised by hypergammaglobulinaemia, autoantibodies, and interface hepatitis. The mainstay of treatment is non-specific immunosuppression, consisting of steroids with or without azathioprine. Although most patients respond satisfactorily to steroid and thiopurine-based treatment regimens, up to 40% relapse and 10% undergo liver transplantation. The cause of autoimmune hepatitis is unknown, but evidence implicates both genetic and environmental factors in its pathogenesis. An imbalance between effector and regulatory mechanisms leads to the breakdown of immune tolerance and the consequent development of an autoimmune attack. Signalling pathways that have been implicated in the pathogenesis of autoimmune hepatitis involve the proinflammatory cytokines interferon-γ, IL-12, tumour necrosis factor-α, IL-6, and IL-23. Numerical and functional defects of regulatory T cells have a permissive role that enables autoimmune liver injury to occur and persist. New therapeutic strategies are needed, with the aim of obtaining long-lasting disease remission without inducing non-specific immunosuppression and a focus on inhibiting the intrahepatic proinflammatory milieu or expanding the pool of regulatory T cells, or both.</p>", "link": "https://www.thelancet.com/journals/langas/article/PIIS2468-1253(20)30328-9/fulltext", "published_date": "2021-02-08T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Gastroenterology & Hepatology", "authors": [ { "author_id": 241567, "given_name": "Rodrigo", "family_name": "Liberal", "ORCID": null, "country": null }, { "author_id": 241569, "given_name": "Ynto S", "family_name": "de Boer", "ORCID": null, "country": null }, { "author_id": 241571, "given_name": "Michael A", "family_name": "Heneghan", "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": [ "Established and novel therapeutic options", "autoimmune hepatitis" ], "doi": "10.1016/S2468-1253(20)30328-9", "access": "restricted", "takeaways": " Autoimmune hepatitis is an immune-mediated disorder characterised by hypergammaglobulinaemia, autoantibodies, and interface hepatitis . The mainstay of treatment is non-specific immunosuppression, consisting of steroids with or without azathioprine . Up to 40% relapse and 10% undergo liver transplantation .", "categories": [] }, { "article_id": 307, "title": "Serum markers of multiple sclerosis - a new approach", "summary": "Optic neuritis (ON) typically manifests with the classical triad of subacute unilateral vision loss, periocular pain and impaired colour vision. It is the first symptom of multiple sclerosis (MS) in about 20% of patients, and approximately half of those experiencing ON will develop MS. However, other inflammatory diseases like neuromyelitis optica spectrum disease (NMOSD), systemic lupus erythematosus (SLE), sarcoidosis, Behchet's disease or infectious diseases like toxoplasmosis can also manifest with ON [[1]]. Thus, it is of crucial importance to improve the diagnosis of early MS. A number of paraclinical measurements can assist in providing a correct diagnosis, most notably magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) examination [[1]]. Specific biomarkers for the differential diagnosis NMOSD have been developed, and most patients are tested for the specific antibodies AQP4-IgG and MOG-IgG on serum cell-based essays. However, no specific serological MS-biomarkers exist. In the present paper recently published in EBioMedicine, Sadam and colleagues [[2]] take a new approach to the question of how to increase diagnostic accuracy in ON patients. By using mimotope variation analysis (MVA), a next generation phage display method, they detected two viral antibody epitopes as possible new biomarkers of MS-risk after ON. The epitopes were gB CMV and VCA p18 EBV. Their approach is interesting for several reasons: First, the biomarkers detected seem to improve the diagnostic accuracy for diagnosing MS in early ON. Second, they could point to pathogenic mechanisms for MS-development. Third, serum biomarkers are available from blood and are much easier to acquire than MRI and lumbar puncture. Interestingly, although the authors have used a hypothesis-free approach, their findings point to two common viral pathogens, that have been linked to MS risk in epidemiological studies. While higher titres against Epstein-Barr virus (EBV) epitopes have been consistently found to increase the risk of developing MS [[3]], Cytomegalovirus (CMV) seropositivity has been negatively associated with MS risk [[4]]. The results of the current paper are in line with these previous findings. Sadam and colleagues [[2]] identified a clear negative association between epitopes against gB CMV and the risk of developing MS after ON. A negative association between previous infections with CMV and the risk of MS has been reported in one large Swedish population-based incident case-control study and in one small multi-ethnic US paediatric MS case-control study [[5]]. A more recent study found, however, inconsistency across ethnic groups [[6]], indicating that there might not be a causal association between CMV and MS. More consistent epidemiological results have been found for the second potential biomarker, VCA p18 EBV [[3],[6]], and some authors have suggested that MS could be considered a rare complication of EBV infection[[7]]. In one large study of early MS, it was found that 100% of the 901 patients were EBV positive, while controls did not reach 100% seropositvity in any of the investigated age cohorts [[8]]. Based on these findings, the authors suggested that negative EBV serology should alert clinicians to consider diagnoses other than MS. Most studies have examined the serum levels of EBNA-1, as a marker of previous EBV infection. In the present paper, the epitope VCA p18 EBV was found to be associated with risk of MS [[2]]. Interestingly, this could be consistent with the results from the Finish Maternity Cohort [[7]]. In this study, offspring of mothers with high VCA IgG during pregnancy had an increased risk of developing MS. The mechanism for how this could affect MS risk is however, still not determined. A number of precautions have to be taken before these biomarkers can be used in a clinical setting. First, the results should be replicated in larger independent cohorts. Preferentially, prospective cohort studies could examine the benefit of incorporating these biomarkers in a risk-evaluation scheme. Second, the biomarkers must be evaluated in different ethnic populations to determine if the findings are consistent across ethnic and regional groups. Based on previous trials, especially CMV antibody responses seem to be determined by ethnicity and possibly not causally linked to the risk of MS. Third, the sensitivity and specificity was only at 75%. We know that about half of all ON patients will go on to develop MS, and the diagnostic accuracy is still far from perfect. These potential biomarkers will probably need to be supplemented with other markers to improve their diagnostic accuracy. In summary, the present study adds to the growing number of findings, indicating that the immunological response to the herpes viruses CMV and EBV are linked to the risk of developing MS. This could reflect unique pathogenic mechanisms for how MS develops and could possibly improve future treatment and diagnosis of the disease.", "link": "https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00022-0/fulltext", "published_date": "2021-01-28T00:00:00Z", "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": 163680, "given_name": "Øivind", "family_name": "Torkildsen", "ORCID": "http://orcid.org/0000-0001-5294-2866", "country": "NO" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Serum markers", "multiple sclerosis", "a new approach" ], "doi": "10.1016/j.ebiom.2021.103229", "access": "open", "takeaways": "", "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": 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 T", "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": 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": 313, "title": "Long-term ocrelizumab in progressive multiple sclerosis", "summary": " The pathophysiology of progressive multiple sclerosis includes acute inflammatory lesion activity, chronic inflammation, and neurodegeneration. 1 The exact relationship between these components remains unclear. Despite success in the development of disease-modifying therapies for relapsing-remitting multiple sclerosis, treatment of progressive multiple sclerosis has proven more difficult. Primary progressive multiple sclerosis is characterised by gradual disability accumulation from disease onset, sometimes with superimposed relapses, or MRI lesion activity, or both. 1 Currently, the anti-CD20 monoclonal antibody ocrelizumab is the only disease-modifying therapy approved to treat primary progressive multiple sclerosis. The evidence for ocrelizumab is based on the results of the ORATORIO phase 3 trial: 2 treatment with intravenous 600 mg of ocrelizumab every 6 months reduced 3-month-confirmed worsening of the Expanded Disability Status Scale (EDSS) score compared with placebo. These primary results were supported by benefit on 6-month-confirmed worsening of EDSS score and on the Timed 25-Foot Walk (T25FW; another measure of neurological disability), MRI lesion activity, and whole brain volume loss.", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30399-9/fulltext", "published_date": "2020-10-29T00:00:00Z", "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": 170212, "given_name": "Deja R", "family_name": "Rose", "ORCID": "http://orcid.org/0000-0003-0423-0551", "country": null }, { "author_id": 151378, "given_name": "Jeffrey A.", "family_name": "Cohen", "ORCID": "http://orcid.org/0000-0001-9245-9772", "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": [ "Long-term ocrelizumab", "progressive multiple sclerosis" ], "doi": "10.1016/S1474-4422(20)30399-9", "access": "restricted", "takeaways": " The anti-CD20 monoclonal antibody ocrelizumab is the only disease-modifying therapy approved to treat primary progressive multiple sclerosis . The evidence for the evidence is based on the results of the ORATORIO phase 3 trial: 2 treatment with intravenous 600 mg of oorelizmab every 6 months reduced 3-month-confirmed worsening of the", "categories": [ { "category_id": 8, "category_description": "", "category_name": "Ocrelizumab", "category_slug": "ocrelizumab", "category_terms": [ "ocrelizumab", "ocrevus" ], "article_count": 234 } ] }, { "article_id": 324, "title": "CXCL13/CXCR5 signalling is pivotal to preserve motor neurons in amyotrophic lateral sclerosis", "summary": "<h2>Abstract</h2><h3>Background</h3><p>CXCL13 is a B and T lymphocyte chemokine that mediates neuroinflammation through its receptor CXCR5. This chemokine is highly expressed by motoneurons (MNs) in Amyotrophic Lateral Sclerosis (ALS) SOD1G93A (mSOD1) mice during the disease, particularly in fast-progressing mice. Accordingly, in this study, we investigated the role of this chemokine in ALS.</p><h3>Methods</h3><p>We used i<i>n vitro</i> and <i>in vivo</i> experimental paradigms derived from ALS mice and patients to investigate the expression level and distribution of CXCL13/CXCR5 axis and its role in MN death and disease progression. Moreover, we compared the levels of CXCL13 in the CSF and serum of ALS patients and controls.</p><h3>Findings</h3><p>CXCL13 and CXCR5 are overexpressed in the spinal MNs and peripheral axons in mSOD1 mice. CXCL13 inhibition in the CNS of ALS mice resulted in the exacerbation of motor impairment (<i>n</i> = 4/group;Mean_Diff.=27.81) and decrease survival (<i>n</i> = 14_Treated:19.2 ± 1.05wks, <i>n</i> = 17_Controls:20.2 ± 0.6wks; 95% CI: 0.4687–1.929). This was corroborated by evidence from primary spinal cultures where the inhibition or activation of CXCL13 exacerbated or prevented the MN loss. Besides, we found that CXCL13/CXCR5 axis is overexpressed in the spinal cord MNs of ALS patients, and CXCL13 levels in the CSF discriminate ALS (<i>n</i> = 30) from Multiple Sclerosis (<i>n</i> = 16) patients with a sensitivity of 97.56%.</p><h3>Interpretation</h3><p>We hypothesise that MNs activate CXCL13 signalling to attenuate CNS inflammation and prevent the neuromuscular denervation. The low levels of CXCL13 in the CSF of ALS patients might reflect the MN dysfunction, suggesting this chemokine as a potential clinical adjunct to discriminate ALS from other neurological diseases.</p><h3>Funding</h3><p>Vaccinex, Inc.; Regione Lombardia (TRANS-ALS)</p>", "link": "https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(20)30473-4/fulltext", "published_date": "2020-11-05T00:00:00Z", "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": 296303, "given_name": "Maria Chiara", "family_name": "Trolese", "ORCID": null, "country": null }, { "author_id": 296304, "given_name": "Alessandro", "family_name": "Mariani", "ORCID": null, "country": null }, { "author_id": 296305, "given_name": "Mineko", "family_name": "Terao", "ORCID": null, "country": null }, { "author_id": 296306, "given_name": "Massimiliano", "family_name": "de Paola", "ORCID": null, "country": null }, { "author_id": 296307, "given_name": "Paola", "family_name": "Fabbrizio", "ORCID": null, "country": null }, { "author_id": 296308, "given_name": "Francesca", "family_name": "Sironi", "ORCID": null, "country": null }, { "author_id": 296309, "given_name": "Mami", "family_name": "Kurosaki", "ORCID": null, "country": null }, { "author_id": 279271, "given_name": "Silvia", "family_name": "Bonanno", "ORCID": null, "country": null }, { "author_id": 296310, "given_name": "Stefania", "family_name": "Marcuzzo", "ORCID": null, "country": null }, { "author_id": 296311, "given_name": "Pia", "family_name": "Bernasconi", "ORCID": null, "country": null }, { "author_id": 148561, "given_name": "Francesca", "family_name": "Trojsi", "ORCID": "http://orcid.org/0000-0002-3790-8018", "country": "IT" }, { "author_id": 285586, "given_name": "Eleonora", "family_name": "Aronica", "ORCID": null, "country": null }, { "author_id": 231097, "given_name": "Caterina", "family_name": "Bendotti", "ORCID": "http://orcid.org/0000-0003-1055-1271", "country": null }, { "author_id": 201495, "given_name": "Giovanni", "family_name": "Nardo", "ORCID": "http://orcid.org/0000-0002-1803-1484", "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": [ "CXCL13/CXCR5 signalling", "motor neurons", "amyotrophic lateral sclerosis" ], "doi": "10.1016/j.ebiom.2020.103097", "access": "open", "takeaways": " CXCL13 is a B and T lymphocyte chemokine that mediates neuroinflammation through its receptor CXCR5 . It is highly expressed by motoneurons (MNs) in Amyotrophic Lateral Sclerosis (ALS) SOD1G93A (mSOD1) mice during the disease .", "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": 320, "title": "Regional and global perspectives on the incidence of multiple sclerosis and neuromyelitis optica and its spectrum disorders from Asia with emphasis on China", "summary": "CNS inflammatory disorders such as multiple sclerosis (MS), neuromyelitis optica/neuromyelitis optica spectrum disorders(NMO/NMOSD) are assuming increasing importance in recent years within Asia [[1]]. In The Lancet Regional Health – Western Pacific, De-Cai Tian and colleagues from China highlight important new data from two nationwide studies on MS/NMO/NMOSD for the first time giving the incidence of MS and NMO/NMOSD in children and adults as well as the burden of disease in terms of hospitalization duration, reimbursement and costs, mortality and common associated comorbidities rarely reported before [[1],[2]]. The study encompasses one of the largest Asian populations sampled to date with better case ascertainments and inclusivity of paediatric and diverse populations. Both studies are large nationwide population-based studies on MS and NMO/NMOSD from a country that houses a fifth of the world's population. Tian et al. accessed information from the national database of the Hospital Quality Monitoring System (HQMS) that covers the entire Chinese population from mainly tertiary hospitals. The authors identified 1665 hospitals covering more than 90% of the tertiary public hospitals, with 11 973 newly diagnosed NMO/NMOSD patients and 9879 pts with MS from 2016–2018[[1],[2]]. Though heterogeneity in methodology prevents head to head comparisons with other studies important points gleaned are as follows: their MS study is large by South-East/East Asian standards although smaller comparatively in absolute numbers than studies from West Asia, United States(US), Continental Europe and Oceania [[3],[4]]. Their NMO/NMOSD study is one of the largest population-based NMO/NMOSD studies to date in terms of absolute numbers [[1],[2],[5],[7],[8]]. It is also noteworthy that this study was done post availability of Anti Aqp4 Ig G antibody testing and the IPND 2015 criteria for NMO/NMOSD resulting in better case ascertainment [[5],[7],[8]]. Further, Tian et al. reported the incidence of MS and NMO/NMOSD in both adults and children. There have been very few studies from within Asia and globally on paediatric MS/NMOSD.6,7 In a recent meta-analysis, global paediatric MS incidence was 0.87 per 100,000 annually which is more than the current study [[6],[7]]. A Japanese study on NMOSD reported rates of 0.06 per 100,000 in paediatrics which is comparable to Tian et al.’s current study [[7]]. Early global MS and NMO/NMOSD studies collected hospital/academic institution-based data within small regions in a country where case ascertainment was abstracted from standard diagnostic criteria. These were good starting points as regional population-based studies but rarely reflected nationwide data. Projecting estimates from one or a few regions to the entire country is of uncertain validity long-term. For instance, a local Malaysian study looking at a small region within the country underestimated the true occurrence of NMO/NMOSD within certain ethnic groups in the country leading to under-representation of cases within the Malay and Indian cohorts [[8]]. Though these efforts at reporting are commendable, it leads to conflicts in health care planning at a national level and unequal disease socio-demographic profiling. A similar nationwide study showed the prevalence of NMO/NMOSD amongst Malays, Chinese and Indians to be 0.9/0.9/0.6 per 100,000 (n=260/256/19) [[9]]. Therefore Tian et al.’s study utilizing the HQMS database, with careful case ascertainment is inclusive and comprehensive as it looks at all regions and increases relevance by covering a large population nationwide rather than extrapolating from a small region [[1],[2]]. The estimated age and sex adjusted incidence for MS for all groups namely adults were comparable to other Asian reports wherein the overall incidence for MS ranged from 0.5 to 0.78 per 100,000 in Malaysia, Taiwan, Japan and Korea respectively [[1],[2],[3],[4],[9],[10]]. However, these rates though increasing are still low compared to high incidence areas in Western Asia like Iran where it is 3.4 per 100,000 and in the US, Europe, Scandinavia, Russia, Australia and New Zealand where it ranges from 1 to >10 per 100,000 [[3],[4],[10]]. This study is further substantiated by the recently published Atlas of MS 3rd Edition, where the prevalence of MS in China is reported to have doubled [[3],[4]]. Thus, though the incidence is increasing in Asia, complex interactions between genetic susceptibility and the environment plausibly accounts for MS partiality to West Asia and Western populations [[3],[4]]. Alternatively, the incidence of NMO/NMOSD in the present study is high and comparable to rates from Japan, Taiwan, Korea and Malaysia ranging from age adjusted 0.287 (adults:0.347 per 100,000) in China to 0.50–0.73 per 100,000 population in other South Asian countries. [[1],[2],[8],[9],[10],[11]] These rates are higher than those reported in Caucasian studies but nearly comparable to Afro–American/Carribean reports [[5],[8]]. Tian et al.’s study interestingly highlights the variability of NMO/NMOSD for certain ethnic groups, gender and regions within Asia with high NMO/NMOSD to MS ratios. The large numbers reported in their Chinese cohort is also seen in other Asian cohorts such as Malaysia where NMOSD is commoner amongst Chinese with NMOSD to MS ratios of 2:1 compared to Indians (MS:NMOSD 8.3:1) and Malays (MS:NMOSD 2:1) [[9]]. A recent Australia-New Zealand study also found Asians to be 3 times more prone for NMO/NMOSD than Caucasians [[11]]. Further, the authors identified a female predominance for both MS and NMOSD which is notably higher amongst their NMOSD patients i.e. 2.0:4.7 (MS: NMOSD). This female preponderance especially in NMOSD is also seen in other Asian MS and NMOSD studies from Japan, Korea, Hong Kong, Taiwan and Malaysia [[5],[9]]. NMO/NMOSD studies from the US, Europe, Australia/New Zealand, West Asia and India also reveal a similar female predominance though less marked than East Asian studies [[5],[8],[11]]. Uniquely, Tian et al.’s study on MS reaffirmed the important effects of latitude seen in Japanese studies, and those from the US, Europe, Russia and Australia/New Zealand [[3],[4]]. However, their study identified not only a negative north–south gradient but also a negative west–east altitude gradient not identified before for MS. This latitude preponderance was not seen in their NMOSD incidence study similar to reports from Australia/New Zealand thus suggesting other genetic factors in pathogenesis [[1],[2],[11]]. In terms of burden of disease, Tian et al.’s study reports mortality rates for MS and NMO/NMOSD of 6 to 7 per 1000 years and the occurrence of associated comorbidities such as hypertension in both conditions. Whilst autoimmune diseases such as SLE/Sjorgen syndromes are seen more with NMOSD than MS. In the past, mortality and morbidity has been scarcely explored in regional studies on MS/NMO/NMOSD [[1],[2]]. The authors also assessed the burden of disease in terms of hospitalization costs, duration and associated comorbidities. This data is vital for budget impact analysis studies for health care planning and medication procurement regionally. Therefore, Tian et al.’s study on hospitalization burden and cost is timely to facilitate MS/NMO/NMOSD resource allocations more so with the advent of newer sophisticated disease modifying therapies, immunosuppressants and biologics for MS and NMO/NMOSD [[1],[2]]. Additionally, their study reports the presence of a universal government based social health insurance which has successfully improved access to care for MS and NMOSD patients in China [[1],[2]]. In summary, the authors provided important updated nationwide information on the epidemiology, burden and cost of disease from China with careful case ascertainment which shows similarities to other regional Asian studies and adds to current worldwide literature on MS and NMO/NMOSD.", "link": "https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(20)30039-0/fulltext", "published_date": "2020-09-29T23:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Regional Health - Western Pacific", "authors": [ { "author_id": 241677, "given_name": "S.", "family_name": "Viswanathan", "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": [ "Regional and global perspectives", "the incidence", "multiple sclerosis", "neuromyelitis optica", "its spectrum disorders", "Asia", "emphasis", "China" ], "doi": "10.1016/j.lanwpc.2020.100039", "access": "open", "takeaways": "", "categories": [] } ] }