Journal of Neurology, Neurosurgery, and Psychiatry最新文献

{"title":"Strong association with remote EBV infection in children with MS as opposed to other acquired demyelinating disorders.","authors":"Sandy Molenaar, Sandra Scherbeijn, Arlette Bruijstens, Michiel Simon Jan Buijze, Joost Smolders, Corine Geurts van Kessel, Rinze Frederik Neuteboom","doi":"10.1136/jnnp-2024-335689","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335689","url":null,"abstract":"<p><strong>Background: </strong>The link between multiple sclerosis (MS) and Epstein-Barr virus (EBV) is well established in adults but less clear in paediatric cases. In addition, the role of EBV and other viral infections in acquired demyelinating syndromes (ADS), including paediatric MS and myelin-oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), remains unknown. This study explores viral infections in children with MS, MOGAD and other ADS.</p><p><strong>Methods: </strong>Serum samples from paediatric patients in a Dutch multicentre ADS cohort were tested for seroprevalence of EBV, cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) using immunoassays.</p><p><strong>Results: </strong>31 children with MS, 26 with MOGAD and 15 with other ADS were included. Nearly all had prior HHV-6 infection (MS 87%, MOGAD 88% and ADS 93%). All children with MS had prior EBV exposure, compared with 50% in MOGAD and 67% in other ADS (p=0.001). EBV nuclear antigen 1 (EBNA-1) and viral capsid antigen antibody levels were particularly high in the MS group. CMV seroprevalence was lower in MS (35%) than in MOGAD (58%, p=0.13), despite older age at onset (16.0 vs 10.5 years). In children with MS, no significant correlations were found between EBNA-1 levels and clinical measures like annualised relapse rate, Expanded Disability Status Scale or the presence of black holes on MRI at baseline.</p><p><strong>Conclusions: </strong>All children with MS show evidence of remote EBV infection, unlike MOGAD and other ADS. EBNA-1 levels are notably high in children with MS. Remote CMV infection appears more common in MOGAD. There are no associations between serology and clinical parameters.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of andexanet alfa for factor Xa inhibitor-associated intracranial haemorrhage.","authors":"Georgios Tsivgoulis, Aristeidis H Katsanos, Michele Romoli, Amrou Sarraj, Christos Krogias, Theodoros Karapanayiotides, Aikaterini Theodorou, Maria Ioanna Stefanou, Carlos A Molina, Marios Themistocleous, Thorsten Steiner, Ashkan Shoamanesh, Lina Palaiodimou","doi":"10.1136/jnnp-2024-335558","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335558","url":null,"abstract":"<p><strong>Background: </strong>Current international guidelines suggest andexanet alfa (AA) for the management of factor Xa inhibitor-associated intracranial haemorrhage (ICH). However, those recommendations are based on low-quality evidence and there is uncertainty regarding the net clinical benefit of AA.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis including available randomised controlled clinical trials (RCTs) and observational studies that investigated efficacy and safety of AA compared with usual care for the treatment of factor Xa inhibitor-associated ICH. Good haemostatic efficacy, defined as haematoma expansion of ≤35% or ≤6 mL, was the primary outcome. Secondary efficacy outcomes were excellent haemostatic efficacy (≤20% haematoma expansion) and good functional outcome (modified Rankin Scale scores 0-3) at follow-up, while safety outcomes were mortality and thrombotic events at follow-up.</p><p><strong>Results: </strong>Eighteen studies (1 RCT) were included comprising a total of 1567 patients treated with AA versus 1969 patients receiving usual care. AA was associated with a higher likelihood of good haemostatic efficacy (RR=1.16; 95% CI=1.06 to 1.26) compared with usual care, while excellent haemostatic efficacy (RR=1.04; 95% CI=0.85 to 1.26) and good functional outcome (RR=0.92; 95% CI=0.53 to 1.62) were similar between the two groups. Regarding safety outcomes, similar rates of mortality (RR=0.77; 95% CI=0.56 to 1.04) and thrombotic events (RR=1.20; 95% CI=0.81 to 1.78) were documented.</p><p><strong>Conclusions: </strong>The present meta-analysis suggests AA is associated with improved haemostatic efficacy compared with usual care, with no significant differences observed in functional and safety outcomes. These findings indicate that AA may have a role in the management of factor Xa inhibitor-associated ICH, although further high-quality studies are needed to better define its net clinical benefit.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex hormone-related factors and the risk of PIRA in women with multiple sclerosis.","authors":"Antonino Giordano, Arianna Giliberti, Ferdinando Clarelli, Kaalindi Misra, Elisabetta Mascia, Melissa Sorosina, Giulia Visentin, Monica Margoni, Lucia Moiola, Maria A Rocca, Massimo Filippi, Federica Esposito","doi":"10.1136/jnnp-2024-335547","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335547","url":null,"abstract":"<p><strong>Background: </strong>Sex-related differences affect multiple sclerosis (MS), but the impact of sex hormones on disease progression remains unclear. We investigated whether sex hormone-related factors influence progression independent of relapse activity (PIRA) in women with MS over a long-term follow-up.</p><p><strong>Methods: </strong>The study analysed 1210 female MS patients from the San Raffaele MS Center using data from an environmental survey (2019-2023). PIRA was defined as 12-week confirmed disability progression independent of recent relapses (<30 days). Cox proportional-hazard models (adjusted for confounding factors) were used to assess the effect of hormone-related factors on PIRA risk.</p><p><strong>Results: </strong>Patients who used oral contraceptives before MS diagnosis had a 26% lower risk of PIRA and a delayed median time to the first PIRA event (9.94 vs 7.5 years; HR=0.74; 95% CI 0.61 to 0.89; p=0.0018). Conversely, menopause at diagnosis (HR=1.82; 95% CI 1.24 to 2.67; p=0.0022) and pregnancy before diagnosis (HR=1.22; 95% CI 1.006 to 1.47; p=0.043) were associated with a shorter time to PIRA. No significant differences were found with abortion, menstrual irregularity or fertility therapy.</p><p><strong>Conclusions: </strong>This study suggests that early oral contraceptives may delay future disability progression, supporting the importance of sex hormones in MS and prompting further prospective investigations on oral contraceptives to slow disease progression.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural correlates of memory deficits in premanifest <i>C9orf72</i>-repeat expansions.","authors":"Jiaze Sun, Joke De Vocht, Daphne Stam, Chih-Hao Lien, Yun-An Huang, Nikita Lamaire, Maarten Laroy, Kristof Vansteelandt, Ann D'Hondt, Maarten J A Van Den Bossche, Rik Vandenberghe, Ronald R Peeters, Stefan Sunaert, Philip van Damme, Mathieu Vandenbulcke, Jan Van den Stock","doi":"10.1136/jnnp-2024-335169","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335169","url":null,"abstract":"<p><strong>Background: </strong>The premanifest stage in carriers of hexanucleotide repeat expansions in the <i>C9orf72</i> gene (C9RE) is associated with memory impairment. The present study examines whether the impairment is general across domains or disproportionately affects specific stimulus categories such as socioemotional events, and its underlying functional neuroanatomy.</p><p><strong>Methods: </strong>This task-based fMRI-study included 21 premanifest C9RE (preC9RE) carriers and 24 controls. Participants encoded stimuli of (emotional and neutral) faces and houses, followed by a recognition task. Using univariate and multivoxel pattern analyses at whole-brain level and region-of-interest level, we investigated the neural change during encoding and retrieval processes, as well as the neural pattern similarity between encoding and retrieval.</p><p><strong>Results: </strong>Compared with controls, the preC9RE group demonstrated poorer performance in memorising faces (U=104, p=0.002), while their ability to memorise houses remained intact. The preC9RE group exhibited distinct neural patterns in the anterior insula during face encoding compared with the controls (accuracy>0.765, p<0.05). During face retrieval, the preC9RE group showed an increased neural response to encoded faces versus new faces in the right anterior insula (U=394, p=0.015). Individuals with preC9RE exhibited reduced encoding-retrieval neural similarity in the salience network specifically related to face stimuli (U=120, p=0.023).</p><p><strong>Conclusions: </strong>The findings reveal functional changes in the salience network related to impaired social memory at the premanifest stage of C9RE. The findings further underscore the high potential of multidimensional neural response patterns as a sensitive biomarker for neurodegenerative functional changes, and the salience network as biomarker for C9RE disease staging.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of body mass index and clinical response in patients receiving ofatumumab for treatment of multiple sclerosis.","authors":"Pia Winter, Franziska Axhausen, Stephanie Wolff, Alice Grizzle Willison, Saskia Räuber, Franz Felix Konen, Stefanie Schreiber, Philipp Schwenkenbecher, Ramona Hagler, Tobias Ruck, Hagen B Huttner, Christoph Kleinschnitz, Mark Pawlitzki, Thomas Skripuletz, Refik Pul, Sven G Meuth, Steffen Pfeuffer","doi":"10.1136/jnnp-2024-335673","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335673","url":null,"abstract":"<p><strong>Background: </strong>The impact of body weight on disability progression rates among patients receiving ofatumumab was not evaluated yet.</p><p><strong>Methods: </strong>Among patients from a multicentre prospective cohort, baseline demographics were compared among body mass index (BMI) quartiles as well as proportions of clinical relapses, MRI lesions and disability worsening during follow-up.</p><p><strong>Results: </strong>536 patients from four centres were included. Baseline demographics were evenly distributed among patients. Proportions of relapses and new/enlarging MRI lesions were comparable among BMI strata.Confirmed disability worsening was significantly more abundant among patients from the 4th BMI quartile (BMI ≥29.2 kg/m²; adjusted HR: 3.33 (95% CI: 1.72 to 6.42; p<0.001). Relapse-associated worsening was not substantially different among relapsing patients from different BMI strata (HR: 1.19 (95% CI: 0.40 to 3.52; p=0.750)). Yet, progression independent from relapse activity was more likely in patients from 4th BMI quartile (HR: 2.00 (95% CI: 1.47 to 2.70; p<0.001)).Body weight (4th body weight quartile: ≥84.5 kg) was not associated with disability worsening (adjusted HR: 1.91 (95% CI: 0.97 to 3.76; p=0.060). Ofatumumab serum levels were lower in patients with higher BMI as well.</p><p><strong>Conclusions: </strong>Inflammatory disease outcomes did not differ but disability progression was more frequent in the highest BMI quartile (BMI >29.2 kg/m²). This was associated with lower ofatumumab serum levels. Since body weight itself was not predictive, we assume that body fat composition is critical for ofatumumab effectiveness.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of natalizumab in secondary progressive multiple sclerosis: analysis of two phase III trials.","authors":"Winston Dzau, Izanne Roos, Tomas Kalincik","doi":"10.1136/jnnp-2024-335495","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335495","url":null,"abstract":"<p><strong>Background: </strong>The ASCEND trial did not find benefit of natalizumab during secondary progressive multiple sclerosis compared with placebo; however, its open-label extension suggests this may be obscured by therapeutic lag.We aimed to compare the efficacy of natalizumab and interferon β-1a in slowing disease progression in secondary progressive multiple sclerosis after accounting for therapeutic lag.</p><p><strong>Methods: </strong>We analysed pooled data from the ASCEND (natalizumab vs placebo) and SPECTRIMS (interferon β-1a vs placebo) trials. Cumulative hazards of 6-month confirmed disability progression during secondary progressive multiple sclerosis were compared using Cox proportional hazards models adjusted for confounding variables. We accounted for therapeutic lag in each patient based on baseline expanded disability status scale, annualised relapse rate and sex. Differences between SPECTRIMS and ASCEND placebo arms were used to adjust the differences between interferon β-1a and natalizumab arms.</p><p><strong>Results: </strong>Baseline characteristics of 1156 patients were similar between SPECTRIMS and ASCEND cohorts, except for a higher proportion of older patients and lower relapse rates in the ASCEND trial. Natalizumab exhibited a lower cumulative hazard of disability progression compared with interferon β-1a (HR 0.15, 95% CI 0.08 to 0.29, p<0.0001). After adjusting for the difference in cumulative hazards between placebo groups (HR 0.36, 95% CI 0.20 to 0.63, p=0.0004), natalizumab remained associated with a lower hazard of disability progression compared with interferon β-1a (HR 0.42, 95% CI 0.22 to 0.77, p=0.0016).</p><p><strong>Conclusion: </strong>After accounting for therapeutic lag and differences between ASCEND and SPECTRIMS trials, natalizumab, compared with interferon β-1a, reduces disability progression during secondary progressive multiple sclerosis.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with outcomes following autologous haematopoietic stem cell transplantation for multiple sclerosis.","authors":"Yassine Noui, Christina Zjukovskaja, Thomas Silfverberg, Per Ljungman, Kim Kultima, Andreas Tolf, Tobias Tolf, Kristina Carlson, Joachim Burman","doi":"10.1136/jnnp-2024-335512","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335512","url":null,"abstract":"<p><strong>Background: </strong>Autologous haematopoietic stem cell transplantation (AHSCT) has emerged as a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS), though patient selection remains challenging. The degree to which disease-modifying therapies (DMTs) and procedure-related complications affect treatment outcomes is unclear. The objective of this study was to investigate the factors that might influence outcomes following AHSCT.</p><p><strong>Methods: </strong>Data from the multicentre, retrospective cohort study Haematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis in Sweden (AutoMS-Swe) were analysed, comprising 174 patients with RRMS who received AHSCT before 1 January 2020. Primary outcomes included inflammatory disease activity, confirmed disability worsening (CDW) and overall evidence of disease activity. Confirmed disability improvement was investigated as a secondary outcome. Associations between variables of interest and outcomes were assessed using univariable Cox proportional hazards models.</p><p><strong>Results: </strong>Patients who received rituximab as the last DMT before AHSCT had a reduced hazard of inflammatory disease activity (HR 0.18, 95% CI 0.04 to 0.78). Epstein-Barr virus detection was associated with a higher hazard of inflammatory disease activity (HR 2.3, 95% CI 1.05 to 5.07). CDW was associated with longer disease durations (HR 1.09, 95% CI 1.00 to 1.19) and was negatively associated with gadolinium-enhancing lesions (HR 0.08, 95% CI 0.01 to 0.64). No CDW events occurred in treatment-naive patients.</p><p><strong>Conclusions: </strong>Prior rituximab treatment appears to be protective against inflammatory activity after AHSCT. Disease duration and gadolinium-enhancing lesions are major determinants of disability following AHSCT.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Another brick in our knowledge of ALS causes: a population-based study of residential clustering.","authors":"Stefano Callegaro, Umberto Manera, Antonio Canosa, Maurizio Grassano, Francesca Palumbo, Sara Cabras, Enrico Matteoni, Francesca Di Pede, Filippo De Mattei, Fabiola De Marchi, Letizia Mazzini, Cristina Moglia, Andrea Calvo, Adriano Chiò, Rosario Vasta","doi":"10.1136/jnnp-2024-335670","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335670","url":null,"abstract":"","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How well do plasma Alzheimer's disease biomarkers reflect the CSF amyloid status?","authors":"Jemma Hazan, Emily Abel, Miguel Rosa Grilo, Deborah Alawode, Ines Laranjinha, Amanda J Heslegrave, Kathy Y Liu, Jonathan M Schott, Robert Howard, Henrik Zetterberg, Nick C Fox","doi":"10.1136/jnnp-2024-334122","DOIUrl":"10.1136/jnnp-2024-334122","url":null,"abstract":"<p><strong>Background: </strong>Can plasma biomarkers as well as cerebrospinal fluid (CSF) perform in the separation of amyloid-beta-positive (Aβ+) vs amyloid-beta-negative (Aβ-) groups across an age range seen in an NHS cognitive disorder clinic?</p><p><strong>Methods: </strong>As part of the routine diagnostic investigation of 111 clinic patients who had contemporaneous blood and CSF samples taken, patients were categorised into Aβ+ and Aβ- groups based on their CSF in an Aβ42/40 ratio. We then evaluated four single molecule array (Simoa) Quanterix assays, quantifying single plasma analytes and ratios (p-tau217, p-tau217/Aβ42 ratio, p-tau181, p-tau181/Aβ42 ratio and Aβ42/40 ratio) in their ability to distinguish between these groups and the effect of age.</p><p><strong>Results: </strong>The median (range) age of participants was 66 (55-79) years with 48 females (43.2%). The areas under the curve (AUC), not accounting for age, for the ability to discriminate Aβ+ from Aβ- groups were plasma p-tau217 AUC=0.94, Aβ42/40 AUC=0.78 and p-tau181 AUC=0.77. Combining p-tau217/Aβ42 increased the AUC to 0.97. The difference between the groups was influenced by age with less separation in older individuals: a significant negative interaction term between age and group for plasma p-tau217 concentrations (-0.037, p=0.013) and p-tau217/Aβ42 ratio (-0.007, p=0.008).</p><p><strong>Conclusions: </strong>There was variable performance of plasma biomarkers to recapitulate the CSF assay. Both p-tau217 and p-tau217/Aβ42 showed excellent promise as surrogates of CSF amyloid status, although with slightly reduced performance in older individuals. There was poorer discriminatory ability for p-tau181 and Aβ42/40. Further research is needed to address potential age-related confounds.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term maintenance of mycophenolate mofetil in anti-NMDA receptor encephalitis (LEARN): a multicentre, open-label, blinded-endpoint, randomised controlled trial.","authors":"Xue Gong, Yue Liu, Yaru Ma, Bo Yan, Dongmei An, Yonghua Guo, Xu Liu, Xingjie Li, Linjun Cai, Xiaolin Deng, Dong Zhou, Jin-Mei Li, Zhen Hong","doi":"10.1136/jnnp-2024-335400","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335400","url":null,"abstract":"<p><strong>Background: </strong>Anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) is a severe autoimmune disorder with high morbidity and mortality. Current treatments have limitations including relapse, highlighting the need for effective maintenance therapy. This study evaluates the efficacy and safety of mycophenolate mofetil (MMF) as long-term adjunctive therapy to first-line treatment in newly diagnosed patients with NMDARE.</p><p><strong>Methods: </strong>We conducted a prospective, randomised, open-label trial in four academic centres in China. Patients aged 14 and older with acute NMDARE, who received first-line treatments within 2 weeks of presentation to the hospital and had a modified Rankin scale (mRS) score of 2 or more, were recruited. Participants were randomly assigned to receive first-line treatment with or without MMF (0.5 g two times per day for 24 months). Primary outcomes included relapse rates and time to relapse, with secondary outcomes including cognitive deficits, treatment response (the proportion of patients with≥1 point improvement in mRS within 4 weeks) and adverse events (AEs).</p><p><strong>Results: </strong>Of 100 patients (52% female; median age 27), those in the MMF group had fewer relapses (5.9% vs 26.5%; p=0.006) and better treatment response (84.3% vs 65.3%; p=0.03). No significant difference was found in long-term functional prognosis at 12 and 24 months. However, MMF patients had less fatigue, cognitive impairment, depression and seizures. AEs were mild-to-moderate, with no deaths or anaphylactic reactions.</p><p><strong>Conclusions: </strong>This study provides Class II evidence that long-term adjunctive treatment of MMF to first-line treatment of NMDARE resulted in a lower risk of relapse and was well tolerated beyond the 24 months of treatment.</p><p><strong>Trial registration number: </strong>ChiCTR2100044362.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}