Journal of Neurology, Neurosurgery, and Psychiatry最新文献

{"title":"C5 complement inhibition and FcRn modulation in generalized myasthenia gravis. Fast-acting but short-lived therapies the use of which should prompt assertive escalation of conventional treatments.","authors":"John McConville","doi":"10.1136/jnnp-2024-334584","DOIUrl":"10.1136/jnnp-2024-334584","url":null,"abstract":"","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"309"},"PeriodicalIF":8.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971276","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":"Neuropathy with anti-myelin-associated glycoprotein antibodies: update on diagnosis, pathophysiology and management.","authors":"Young Gi Min, Andrea Visentin, Chiara Briani, Yusuf A Rajabally","doi":"10.1136/jnnp-2024-334678","DOIUrl":"10.1136/jnnp-2024-334678","url":null,"abstract":"<p><p>Antimyelin-associated glycoprotein (MAG) neuropathy is a rare autoimmune demyelinating peripheral neuropathy caused by IgM autoantibodies targeting MAG. The typical presentation is that of a slowly progressive, distal, length-dependent, predominantly sensory, sometimes ataxic neuropathy, frequently accompanied by upper limb tremor. Distal motor weakness may subsequently occur. The clinical presentation may vary and rarely be consistent with that of typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), as well as have an aggressive and rapidly disabling course. The diagnosis of anti-MAG neuropathy is based on the detection of anti-MAG antibodies through ELISA or western blot analysis, primarily in presence of an IgM monoclonal gammopathy. Anti-MAG neuropathy may occur without or with haematological malignancy. Electrophysiology is characteristic of a predominantly distal demyelinating neuropathy. Intravenous immunoglobulins and plasma exchange have unproven benefits, but may provide short-term effects. Cytotoxic therapies are commonly used, although without an evidence base. Rituximab, an anti-B-cell monoclonal antibody was studied in two randomised controlled trials, neither of which achieved their primary outcome. However, a meta-analysis of these two studies demonstrated improvement of disability at 8-12 months. A recent trial with lenalidomide was interrupted prematurely due to a high rate of venous thromboembolism. There are currently two ongoing trials with Bruton's tyrosine kinase inhibitors. Symptom control is otherwise frequently needed. Outcome measures used for other inflammatory neuropathies present limitations in anti-MAG neuropathy. International registries such as the planned IMAGiNe study may, in future, provide answers to the many remaining questions.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"340-349"},"PeriodicalIF":8.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807271","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":"Total bilirubin modified the association between diabetes and stroke: a cross-sectional study from NHANES 2011-2016.","authors":"Zhang Xia, Guozheng Xu, Mingyang Zhao, Yuhao Li, Peiyu Ye, Yijian Liu, Herbert Y Gaisano, Yan He","doi":"10.1136/jnnp-2024-334408","DOIUrl":"10.1136/jnnp-2024-334408","url":null,"abstract":"<p><strong>Background: </strong>Total bilirubin (TBIL) has antioxidant and anti-inflammatory properties. This study aimed to determine whether elevated TBIL could modify the association between diabetes and stroke.</p><p><strong>Method: </strong>Data were obtained from the National Health and Nutrition Examination Survey 2011-2016. TBIL was stratified by median (10.3 µmol/L). The association between diabetes and stroke was quantified using multivariable logistic regression models. The cut-off concentration for the presence of TBIL modification effects was identified by Johnson-Neyman analyses. Mediation analyses were performed to determine the influence of TBIL on mediating factors that mediate the relationship between diabetes and stroke.</p><p><strong>Results: </strong>This cross-sectional study included 16 130 participants, with the mean age of 46.8±0.4 years and 48.5% of men. Diabetes was associated with the presence of stroke at TBIL <10.3 µmol/L (OR=2.19, 95% CI 1.58 to 3.05) but not at TBIL ≥10.3 µmol/L (OR=1.27, 95% CI 0.85 to 1.88) after adjustment for confounders. Above associations were significantly different between the two TBIL concentrations (<i>P</i> for interaction=0.03). Moreover, the modification effect of TBIL specifically occurred in men (<i>P</i> for interaction=0.02) rather than in women (<i>P</i> for interaction=0.08). The cut-off concentration for the presence of TBIL modification effects was 17.05 µmol/L. Additionally, the TBIL of ≥10.3 µmol/L inhibited mediating effects of hypersensitive C reactive protein (mediating effect=0.03, 95% CI -0.15 to 0.22, <i>P</i>=0.72) and systemic immune-inflammation index (mediating effect=0.01, 95% CI -0.01 to 0.04, <i>P</i>=0.29) as compared with the TBIL of <10.3 µmol/L.</p><p><strong>Conclusions: </strong>Elevated TBIL modified the association between diabetes and stroke through inhibiting mediating effects of inflammatory factors.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"406-414"},"PeriodicalIF":8.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132958","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":"Efgartigimod efficacy and safety in refractory myasthenia gravis: UK's first real-world experience.","authors":"Joana Moniz Dionísio, Philip Ambrose, Georgina Burke, Maria Elena Farrugia, Pablo Garcia-Reitboeck, Channa Hewamadduma, Marguerite Hill, Robin S Howard, Saiju Jacob, Dimitri Kullmann, Maria Isabel Leite, James Miller, Ashwin Pinto, Jane Pritchard, Thomas Riswick, Sivakumar Sathasivam, Narmathey Thambirajah, Stuart Viegas, Fiona Norwood, Jennifer Spillane","doi":"10.1136/jnnp-2024-334086","DOIUrl":"10.1136/jnnp-2024-334086","url":null,"abstract":"<p><strong>Background: </strong>We report our experience of patients with generalised myasthenia gravis (gMG) treated with efgartigimod, an neonatal Fc receptor antagonist, under the Early Access to Medicine Scheme (EAMS) in the UK.</p><p><strong>Methods: </strong>Data from all UK patients treated with efgartigimod under the EAMS July 2022 to July 2023 were collected retrospectively. Efgartigimod was administered as per the ADAPT protocol (consisting of a treatment cycle of four infusions at weekly intervals with further cycles given according to clinical need).</p><p><strong>Results: </strong>48 patients with acetylcholine receptor antibody-positive gMG were treated in 12 centres. Most (75%) were female and most had a disease duration of over 10 years. The average MG-Activities of Daily Living (ADL) score at baseline was 11.2. Most (72.9%) patients had undergone thymectomy. 77.0% were taking prednisolone at baseline. All patients had used non-steroidal immunosuppressant treatments, the average number tried was 2.6 (range 1-6). 51% had received rituximab. 54.2% of patients required regular intravenous immunoglobulin/plasma exchange.75% of patients had a mean reduction in the MG-ADL of≥2 points in the first cycle and this remained stable throughout the study. The mean intracycle reduction in the MG-ADL score in the first, second, third and fourth cycles were -4.6 to -3.9, -3.4 and -4.2, respectively. Side effects were generally mild. No rescue treatments were required. At the end of the study, 96% of patients remained on efgartigimod.</p><p><strong>Conclusion: </strong>Efgartigimod is a safe and effective treatment for patients with refractory, treatment-resistant gMG.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"322-328"},"PeriodicalIF":8.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971253","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":"C5 complement inhibition versus FcRn modulation in generalised myasthenia gravis.","authors":"Niklas Huntemann, Lea Gerischer, Meret Herdick, Christopher Nelke, Frauke Stascheit, Sarah Hoffmann, Menekse Öztürk, Christina B Schroeter, Sophie Lehnerer, Maike Stein, Charlotte Schubert, Christiane Schneider-Gold, Steffen Pfeuffer, Heidrun H Krämer, Franz Felix Konen, Thomas Skripuletz, Marc Pawlitzki, Stefanie Glaubitz, Jana Zschüntzsch, Valerie Scherwietes, Andreas Totzeck, Tim Hagenacker, Sven G Meuth, Andreas Meisel, Tobias Ruck","doi":"10.1136/jnnp-2024-334404","DOIUrl":"10.1136/jnnp-2024-334404","url":null,"abstract":"<p><strong>Background: </strong>Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions, leading to fluctuating muscle weakness. While many patients respond well to standard immunosuppression, a substantial subgroup faces ongoing disease activity. Emerging treatments such as complement factor C5 inhibition (C5IT) and neonatal Fc receptor (FcRn) antagonism hold promise for these patients. However, the current landscape is hindered by a paucity of comparative data that is crucial for treatment decisions.</p><p><strong>Objective: </strong>This study aims to compare the effectiveness and safety of C5IT and FcRn antagonists in a real-world setting.</p><p><strong>Methods: </strong>A retrospective analysis of 153 MG patients from 8 German specialised MG centres receiving either C5IT (26 eculizumab, 80 ravulizumab) or efgartigimod (47 patients) was conducted. Propensity score matching (PSM) was employed to compare changes in MG-specific outcome parameters within the first 6 months after treatment initiation, along with safety profiles and concomitant MG therapy.</p><p><strong>Results: </strong>Both treatment strategies led to rapid clinical improvements and substantial reductions in prednisolone doses. However, insufficient response was noted in 20%-49.1% of patients based on Quantitative MG and MG Activities of Daily Living (MG-ADL) scores. We did not identify any new safety concerns. After PSM, 40 patients remained in each group. In both cohorts, reductions in MG-ADL as prespecified primary study endpoint were comparable. Moreover, analyses of secondary outcome parameters demonstrated similar results for C5IT versus FcRn.</p><p><strong>Conclusion: </strong>In contrast to current meta-analyses and indirect comparisons of clinical trial data, our real-world study demonstrates comparable efficacy and safety of C5IT and FcRn antagonism in MG.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"310-321"},"PeriodicalIF":8.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple metal exposures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study.","authors":"Dae-Gyu Jang, John F Dou, Emily J Koubek, Samuel Teener, Lili Zhou, Kelly M Bakulski, Bhramar Mukherjee, Stuart A Batterman, Eva L Feldman, Stephen A Goutman","doi":"10.1136/jnnp-2024-333978","DOIUrl":"10.1136/jnnp-2024-333978","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival and exposure sources.</p><p><strong>Methods: </strong>Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry. ORs and HRs for each metal were computed using risk and survival models. Environmental risk scores (ERS) were created to evaluate the association between exposure mixtures and ALS risk and survival and exposure source. ALS (ALS-PGS) and metal (metal-PGS) polygenic risk scores were constructed from an independent genome-wide association study and relevant literature-selected single-nucleotide polymorphisms.</p><p><strong>Results: </strong>Plasma and urine samples from 454 ALS and 294 control participants were analysed. Elevated levels of individual metals, including copper, selenium and zinc, significantly associated with ALS risk and survival. ERS representing metal mixtures strongly associated with ALS risk (plasma, OR=2.95, CI=2.38-3.62, p<0.001; urine, OR=3.10, CI=2.43-3.97, p<0.001) and poorer ALS survival (plasma, HR=1.37, CI=1.20-1.58, p<0.001; urine, HR=1.44, CI=1.23-1.67, p<0.001). Addition of the ALS-PGS or metal-PGS did not alter the significance of metals with ALS risk and survival. Occupations with high potential of metal exposure associated with elevated ERS. Additionally, occupational and non-occupational metal exposures were associated with measured plasma and urine metals.</p><p><strong>Conclusion: </strong>Metals in plasma and urine associated with increased ALS risk and reduced survival, independent of genetic risk, and correlated with occupational and non-occupational metal exposures. These data underscore the significance of metal exposure in ALS risk and progression.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"329-339"},"PeriodicalIF":8.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897642","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":"Sports-related concussion not associated with long-term cognitive or behavioural deficits: the PROTECT-TBI study.","authors":"Matthew Joseph Lennon, Grant Rigney, Byron Creese, Dag Aarsland, Adam Hampshire, Clive Ballard, Anne Corbett, Vanessa Raymont","doi":"10.1136/jnnp-2024-334039","DOIUrl":"10.1136/jnnp-2024-334039","url":null,"abstract":"<p><strong>Background: </strong>The cognitive effects of sports-related concussion (SRC) have been the subject of vigorous debate but there has been little research into long-term outcomes in non-athlete populations.</p><p><strong>Methods: </strong>This cohort study of UK community-dwelling adults (aged 50-90 years) was conducted between November 2015 and November 2020, with up to 4 years annual follow-up (n=15 214). Lifetime history of concussions was collected at baseline using the Brain Injury Screening Questionnaire. The first analysis grouped participants by type of concussion (no concussion, only SRC, only non-SRC (nSRC), mixed concussions (both SRC and nSRC)) and the second grouped the participants by number (0, 1, 2 or 3+ SRC or nSRC). Mixed models were used to assess the effect of concussion on outcomes including four cognitive domains and one behavioural measure (Mild Behavioural Impairment-C).</p><p><strong>Results: </strong>Analysis of the included participants (24% male, mean age=64) at baseline found that the SRC group had significantly better working memory (B=0.113, 95% CI 0.038, 0.188) and verbal reasoning (B=0.199, 95% CI 0.092, 0.306) compared with those without concussion. Those who had suffered one SRC had significantly better verbal reasoning (B=0.111, 95% CI 0.031, 0.19) and attention (B=0.115, 95% CI 0.028, 0.203) compared with those with no SRC at baseline. Those with 3+ nSRCs had significantly worse processing speed (B=-0.082, 95% CI -0.144 to -0.019) and attention (B=-0.156, 95% CI -0.248 to -0.063). Those with 3+ nSRCs had a significantly worse trajectory of verbal reasoning with increasing age (B=-0.088, 95% CI -0.149 to -0.026).</p><p><strong>Conclusions: </strong>Compared with those reporting no previous concussions, those with SRC had no cognitive or behavioural deficits and seemed to perform better in some tasks. As indicated by previous studies, sports participation may confer long-term cognitive benefits.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"397-405"},"PeriodicalIF":8.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and prevalence of functional neurological disorder: a systematic review.","authors":"Sara A Finkelstein, Clare Diamond, Alan Carson, Jon Stone","doi":"10.1136/jnnp-2024-334767","DOIUrl":"10.1136/jnnp-2024-334767","url":null,"abstract":"<p><strong>Background: </strong>Robust epidemiological data regarding population incidence and prevalence of functional neurological disorder (FND) would be helpful with regards to resource allocation and planning for this disorder, particularly given high symptom burden and high healthcare utilisation. We therefore aimed to systematically review and synthesise available data on FND incidence and prevalence.</p><p><strong>Methods: </strong>PubMed was searched to identify original research articles that reported on the incidence or prevalence of FND. Risk of bias assessment for each study was conducted. Incidence and prevalence rates of FND were additionally estimated by extrapolating data from low risk of bias studies on functional seizures alone.</p><p><strong>Results: </strong>Thirty-nine articles were included. Nineteen reported on FND incidence, 21 reported on prevalence. Comparison between studies was difficult due to methodological differences and significant heterogeneity of incidence and prevalence estimates was found. The incidence of FND was estimated at 10-22/100 000, while minimum prevalence of FND was estimated at 80-140/100 000, with a possible range of 50-1600/100 000. Incidence of paediatric FND was estimated to be between 1 and 18/100 000.</p><p><strong>Conclusions: </strong>The range of incidence and prevalence varies widely across studies, with significant heterogeneity among studies and most studies likely provide underestimates due to methodological challenges. However, using our best method as a conservative estimate, there are likely a minimum of 50-100 000 people with FND in the UK, as an example country. Given that FND appears to be more prevalent than many other well-known and well-funded neurological disorders, incidence and prevalence data suggested here indicate the need for greater research and clinical funding allocation to FND programmes.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"383-395"},"PeriodicalIF":8.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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}