Multiple sclerosis (Houndmills, Basingstoke, England)最新文献

{"title":"Comparative effectiveness of rituximab and cladribine in relapsing-remitting multiple sclerosis: A target trial emulation.","authors":"Brit Ellen Rød, Einar A Høgestøl, Øivind Torkildsen, Kjetil Bjørnevik, Jon Michael Gran, Mathias H Øverås, Marton König, Kjell-Morten Myhr, Stig Wergeland, Gro O Nygaard","doi":"10.1177/13524585251342727","DOIUrl":"10.1177/13524585251342727","url":null,"abstract":"<p><strong>Background: </strong>Head-to-head comparisons of high-efficacy therapies for relapsing-remitting multiple sclerosis (RRMS) are lacking. We conducted a target trial emulation to compare the long-term effectiveness of rituximab and cladribine.</p><p><strong>Methods: </strong>We estimated the effect of initiating treatment with rituximab versus cladribine using observational data from the Norwegian MS Registry and Biobank at two university hospitals with different treatment strategies. Cumulative incidence and risk differences (RDs) were estimated using weighted Kaplan-Meier estimators, adjusting for baseline covariates. The primary outcome was magnetic resonance imaging (MRI) disease activity, with secondary outcomes including relapses and safety.</p><p><strong>Results: </strong>The study included 285 patients, 159 receiving rituximab and 126 cladribine, with a median follow-up of 4.5 years (interquartile range (IQR): 4.2-4.7). The 4-year risk of new MRI disease activity was 17% (95% confidence interval (CI): 11-23) for rituximab-treated patients and 57% (95% CI: 44-66) for cladribine-treated patients, yielding an RD of 40 percentage-points (95% CI: 28-50). The 4-year RD for relapse was 12 percentage-points (95% CI: 4-19). The incidence of hospitalizations related to potential adverse events was 6.0 per 100 person-years for rituximab and 4 per 100 person-years for cladribine.</p><p><strong>Conclusion: </strong>These findings suggest that rituximab has superior effectiveness compared to cladribine during a median follow-up of 4.5 years.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"13524585251342727"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The path to prevention of multiple sclerosis: Considerations for Epstein-Barr virus vaccine-based prevention studies.","authors":"Gregory K Zane, Anna Sutton, Amanda Brumwell, Md Rezaul Hossain, Stephen E Hawes, Gavin Giovannoni, Ellen M Mowry, Steven Jacobson, Jeffrey I Cohen, Bruce Bebo, Rena C Patel","doi":"10.1177/13524585251340812","DOIUrl":"https://doi.org/10.1177/13524585251340812","url":null,"abstract":"<p><p>Recent advancements in our understanding of the association between Epstein-Barr virus (EBV) and multiple sclerosis (MS), along with progress in EBV vaccine development, warrant serious considerations of future EBV vaccine-based MS-prevention studies. The clinical, financial, logistical, and technological considerations for designing and conducting retrospective and/or prospective prevention studies with the primary objective of evaluating the effectiveness of EBV vaccines in preventing MS and other EBV-associated sequelae are presented here. As implementation of these studies may require hundreds of thousands of participants, millions of dollars, and decades to observe if meaningful reductions in MS incidence occur, alternative approaches using pragmatic phase IV, post-licensure study designs focused on either the prevention of MS or infectious mononucleosis (IM), a common clinical manifestation of EBV infection that has been associated with increased risk of MS, are also explored. Current knowledge gaps in technology, funding, and research that must be addressed for a study protocol to be successfully designed and implemented are also discussed.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"13524585251340812"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-varying connectivity of the precuneus and its association with cognition and depressive symptoms in neuromyelitis optica: A pilot MRI study.","authors":"Laura Cacciaguerra,&nbsp;Damiano Mistri,&nbsp;Paola Valsasina,&nbsp;Vittorio Martinelli,&nbsp;Massimo Filippi,&nbsp;Maria A Rocca","doi":"10.1177/13524585221107125","DOIUrl":"https://doi.org/10.1177/13524585221107125","url":null,"abstract":"<p><strong>Background: </strong>The precuneus is involved in cognition and depression; static functional connectivity (SFC) abnormalities of this region have been observed in neuromyelitis optica spectrum disorders (NMOSD). Time-varying functional connectivity (TVC) underpins dynamic variations of brain connectivity.</p><p><strong>Objective: </strong>The aim of this study was to explore precuneus SFC and TVC in NMOSD patients and their associations with neuropsychological features.</p><p><strong>Methods: </strong>This retrospective study includes 27 NMOSD patients and 30 matched healthy controls undergoing resting state functional magnetic resonance imaging (MRI) and a neuropsychological evaluation of cognitive performance and depressive symptoms. A sliding-window correlation analysis using bilateral precuneus as seed region assessed TVC, which was quantified by the standard deviation of connectivity across windows. Mean connectivity indicated SFC.</p><p><strong>Results: </strong>Compared to controls, patients had reduced SFC between precuneus, temporal lobe, putamen and cerebellum, and reduced TVC between precuneus and prefronto-parietal-temporo-occipital cortices and caudate. Patients also had increased intra-precuneal TVC and increased TVC between the precuneus and the temporal cortex. More severe depressive symptoms correlated with increased TVC between the precuneus and the temporal lobe; worse cognitive performance mainly correlated with higher TVC between the precuneus and the parietal lobe.</p><p><strong>Conclusion: </strong>TVC rather than SFC of the precuneus correlates with NMOSD neuropsychological features; different TVC abnormalities underlie depressive symptoms and cognitive impairment.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"2057-2069"},"PeriodicalIF":5.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/f8/10.1177_13524585221107125.PMC9574904.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40591137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cladribine-induced liver injury: Implications for practice.","authors":"Wallace J Brownlee","doi":"10.1177/13524585221125370","DOIUrl":"https://doi.org/10.1177/13524585221125370","url":null,"abstract":"","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"2146"},"PeriodicalIF":5.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40379555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute idiosyncratic liver injury after Cladribine treatment for multiple sclerosis: first case report and review on associated hepatic disorders.","authors":"Lorenzo Saraceno,&nbsp;Fiammetta Pirro,&nbsp;Rosa Stigliano,&nbsp;Elio Clemente Agostoni,&nbsp;Alessandra Protti","doi":"10.1177/13524585221125360","DOIUrl":"https://doi.org/10.1177/13524585221125360","url":null,"abstract":"<p><p>In recent years, several disease-modifying therapies have been developed for the treatment of multiple sclerosis (MS). Cladribine transiently depletes B and T lymphocytes, with subsequent gradual cell recovery. No cases are reported in literature describing Cladribine drug-induced liver injury (DILI). We describe the case of a 19-year-old woman who developed acute idiosyncratic liver injury 12 days after treatment with Cladribine. Post-marketing adverse event reporting is of paramount importance to allow an early recognition and treatment. Moreover, evaluation of the physiopathological mechanism underlying drug-induced hepatic toxicity can provide clinicians with valuable instruments for prevention and treatment.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"2142-2145"},"PeriodicalIF":5.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40379931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory synaptic loss drives network changes in multiple sclerosis: An ex vivo to in silico translational study.","authors":"Marijn Huiskamp,&nbsp;Svenja Kiljan,&nbsp;Shanna Kulik,&nbsp;Maarteen E Witte,&nbsp;Laura E Jonkman,&nbsp;John Gjm Bol,&nbsp;Geert J Schenk,&nbsp;Hanneke E Hulst,&nbsp;Prejaas Tewarie,&nbsp;Menno M Schoonheim,&nbsp;Jeroen Jg Geurts","doi":"10.1177/13524585221125381","DOIUrl":"https://doi.org/10.1177/13524585221125381","url":null,"abstract":"<p><strong>Background: </strong>Synaptic and neuronal loss contribute to network dysfunction and disability in multiple sclerosis (MS). However, it is unknown whether excitatory or inhibitory synapses and neurons are more vulnerable and how their losses impact network functioning.</p><p><strong>Objective: </strong>To quantify excitatory and inhibitory synapses and neurons and to investigate how synaptic loss affects network functioning through computational modeling.</p><p><strong>Methods: </strong>Using immunofluorescent staining and confocal microscopy, densities of glutamatergic and GABAergic synapses and neurons were compared between post-mortem MS and non-neurological control cases. Then, a corticothalamic biophysical model was employed to study how MS-induced excitatory and inhibitory synaptic loss affect network functioning.</p><p><strong>Results: </strong>In layer VI of normal-appearing MS cortex, excitatory and inhibitory synaptic densities were significantly lower than controls (reductions up to 14.9%), but demyelinated cortex showed larger losses of inhibitory synapses (29%). In our computational model, reducing inhibitory synapses impacted the network most, leading to a disinhibitory increase in neuronal activity and connectivity.</p><p><strong>Conclusion: </strong>In MS, excitatory and inhibitory synaptic losses were observed, predominantly for inhibitory synapses in demyelinated cortex. Inhibitory synaptic loss affected network functioning most, leading to increased neuronal activity and connectivity. As network disinhibition relates to cognitive impairment, inhibitory synaptic loss seems particularly relevant in MS.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"2010-2019"},"PeriodicalIF":5.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40394367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking the MS brain: Synaptic loss and computational modelling of brain networks.","authors":"Massimiliano Di Filippo,&nbsp;Andrea Mancini","doi":"10.1177/13524585221124307","DOIUrl":"https://doi.org/10.1177/13524585221124307","url":null,"abstract":"Extensive clinical and preclinical research over the past decades significantly improved our understanding of the immunopathogenesis of multiple sclerosis (MS) and highlighted how neuronal, axonal, and synaptic damage accompanies inflammatory processes since the earliest disease stages.1 It is still challenging, however, to decipher how such different factors interact and underpin the heterogeneity of MS clinical expression. Purely quantitative approaches, based on the evaluation of the extent of grey matter damage and demyelinating plaque burden, are sometimes contradicted by patterns of clinical-radiological dissociation, highlighting the relevance of individual coping mechanisms in each person with MS. Accordingly, new interpretative models are required to account for the heterogeneity of clinical phenotypes and manifestations in people with MS (PwMS). In this scenario, modern network science offers a different point of view. Brain networks can be considered as cost-efficient small-world networks, displaying high connectedness and efficient global integration, organized with hierarchical modularity and able to offer a proper balance between the segregation and integration of information.2 Structural or functional impairment of highly connected hubs may alter the function of the whole network, triggering compensatory changes in network activity that may represent maladaptive responses with progressive hub overload and hub failure.2 This interpretative model can be applied to different neurological disorders, with MS being a paradigmatic example, due to the presence of multifocal demyelinating lesions with a network ‘disconnecting’ effect3 and the more recent evidence of both functional and structural alterations of synaptic connections.4,5 In this issue, Huiskamp and colleagues6 provide a histological characterization of neuronal, excitatory and inhibitory synaptic densities in PwMS, testing through computational modelling how MS-related synaptic loss might affect brain network functioning. The authors found that excitatory and inhibitory synaptic densities were significantly reduced in the cortical layer VI of normal-appearing and demyelinated MS cortex, with respect to nonneurological controls. Interestingly, despite the fact that excitatory and inhibitory synapses were similarly reduced in normal-appearing MS cortex, the reduction was significantly larger for inhibitory synapses in demyelinated cortex. By testing such excitatory and inhibitory synaptic loss in a cortico-thalamic meanfield model that is thought to accurately mimic largescale brain dynamics, the authors show that inhibitory synapses impact network functioning more profoundly, leading to a disinhibitory increase in functional connectivity and neuronal activity. In this study, the authors translated histological findings on synaptic damage into macroscopic functional network analyses, showing that even slight changes in cortical excitatory and, especially, inhibitory synaptic de","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1999-2000"},"PeriodicalIF":5.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33518559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bright spotty lesions as an imaging marker for neuromyelitis optica spectrum disorder.","authors":"Sara Salama,&nbsp;Michael Levy","doi":"10.1177/1352458521994259","DOIUrl":"https://doi.org/10.1177/1352458521994259","url":null,"abstract":"<p><p>Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory demyelinating disorder of the central nervous system (CNS). Aquaporin-4 (AQP4) antibodies in the serum are highly specific for the diagnosis of NMOSD, but the sensitivity remains under 90% allowing for diagnosis of AQP4 IgG seronegative disease. It remains of crucial importance to identify seronegative NMOSD myelitis as early as the first attack to initiate long-term treatment that will reduce future relapses and disability and to avoid potentially harmful treatments such as those of multiple sclerosis (MS). Over the years, many spinal imaging features have been reported to favour the diagnosis of NMOSD, but only longitudinally extensive transverse myelitis (LETM) was specific enough to make the diagnostic criteria in the AQP4 IgG seronegative cases. Bright spotty lesions (BSLs), which are defined as hyperintense lesions on axial T2-weighted images and sometimes associated with T1 low signal, are now reported to have a higher specificity and sensitivity compared to LETM in predicting a diagnosis of NMOSD against other causes of myelitis. In the review, we aim to highlight the position of BSLs in diagnosing NMOSD as well as its possible role as a prognostic factor for the clinical outcome.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1663-1666"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1352458521994259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25408506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"All anti-CD20 monoclonal antibodies have similar efficacy and risks: No.","authors":"Finn Sellebjerg,&nbsp;Jeppe Romme Christensen","doi":"10.1177/13524585221103729","DOIUrl":"https://doi.org/10.1177/13524585221103729","url":null,"abstract":"Treatment with the B cell-depleting anti-CD20 monoclonal antibodies (mAb) ocrelizumab, ofatumumab, rituximab and ublituximab results in profound reductions in magnetic resonance imaging disease activity in multiple sclerosis (MS). Data on clinical and magnetic resonance imaging (MRI) efficacy from Phase 3 studies are in the same range for ocrelizumab and ofatumumab and data from Phase 2 studies also indicate similar effect and safety for rituximab and ublituximab.1,2 Although all four mAbs are highly efficacious in depleting circulating B cells and in reducing disease activity, they may differ in their safety profile and in their ability to prevent worsening of disability and disease progression.","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1845-1846"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40371106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial.","authors":"Bruce Ac Cree,&nbsp;Krzysztof W Selmaj,&nbsp;Lawrence Steinman,&nbsp;Giancarlo Comi,&nbsp;Amit Bar-Or,&nbsp;Douglas L Arnold,&nbsp;Hans-Peter Hartung,&nbsp;Xavier Montalbán,&nbsp;Eva K Havrdová,&nbsp;James K Sheffield,&nbsp;Neil Minton,&nbsp;Chun-Yen Cheng,&nbsp;Diego Silva,&nbsp;Ludwig Kappos,&nbsp;Jeffrey A Cohen","doi":"10.1177/13524585221102584","DOIUrl":"https://doi.org/10.1177/13524585221102584","url":null,"abstract":"<p><strong>Background: </strong>Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for treatment of relapsing forms of MS.</p><p><strong>Objective: </strong>To characterize long-term safety and efficacy of ozanimod.</p><p><strong>Methods: </strong>Patients with relapsing MS who completed a phase 1‒3 ozanimod trial were eligible for an open-label extension study (DAYBREAK) of ozanimod 0.92 mg/d. DAYBREAK began 16 October 2015; cutoff for this interim analysis was 2 February 2021.</p><p><strong>Results: </strong>This analysis included 2494 participants with mean 46.8 (SD 11.9; range 0.033‒62.7) months of ozanimod exposure in DAYBREAK. During DAYBREAK, 2143 patients (85.9%) had treatment-emergent adverse events (TEAEs; similar in nature to those in the parent trials), 298 (11.9%) had a serious TEAE, and 75 (3.0%) discontinued treatment due to TEAEs. Serious infections (2.8%), herpes zoster infections (1.7%), confirmed macular edema cases (0.2%), and cardiac TEAEs (2.8%) were infrequent. Adjusted annualized relapse rate was 0.103 (95% confidence interval, 0.086‒0.123). Over 48 months, 71% of patients remained relapse free. Adjusted mean numbers of new/enlarging T2 lesions/scan and gadolinium-enhancing lesions were low and similar across parent trial treatment subgroups.</p><p><strong>Conclusions: </strong>This long-term extension of ozanimod trials confirmed a favorable safety/tolerability profile and sustained benefit on clinical and magnetic resonance imaging measures of disease activity.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1944-1962"},"PeriodicalIF":5.8,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b7/e0/10.1177_13524585221102584.PMC9493410.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40408128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}