Journal of Neurology, Neurosurgery, and Psychiatry最新文献

{"title":"Low-density lipoprotein cholesterol levels and risk of incident dementia: a distributed network analysis using common data models.","authors":"Minwoo Lee, Kyung Joo Lee, Jinseob Kim, Dong Yun Lee, Rae Woong Park, Sang Youl Rhee, Jae Myung Cha, Hyeon-Jong Yang, Jae-Won Jang, Seunguk Jung, Jeeun Lee, Sang-Hwa Lee, Chulho Kim, Jong-Seok Bae, Yeo Jin Kim, Ju-Hun Lee, Hyoeun Bae, Yerim Kim","doi":"10.1136/jnnp-2024-334708","DOIUrl":"https://doi.org/10.1136/jnnp-2024-334708","url":null,"abstract":"<p><strong>Background: </strong>The link between low-density lipoprotein cholesterol (LDL-C) levels and dementia risk is poorly understood, with conflicting evidence on the role of LDL-C and the impact of statin therapy on cognitive outcomes. Thus, we aimed to examine the association between low-density LDL-C levels and the risk of dementia and assess the influence of statin therapy.</p><p><strong>Methods: </strong>We retrospectively analysed data from 11 university hospitals participating in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). Participants with a prior diagnosis of dementia or those with <180 days of observation before cohort inclusion, and those included in both cohorts were excluded. The primary outcome was all-cause dementia, with the secondary outcome being Alzheimer's disease-related dementia (ADRD). The study utilised 1:1 propensity score matching to compare individuals with LDL-C levels below 70 mg/dL (1.8 mmol/L) against those with levels above 130 mg/dL (3.4 mmol/L), resulting in a primary analysis cohort of 108 980 matched patients. Secondary analyses further examined LDL-C thresholds below 55 mg/dL (1.4 mmol/L) and the influence of statin use.</p><p><strong>Results: </strong>The LDL-C levels below 70 mg/dL (1.8 mmol/L) were associated with a 26% reduction in the risk of all-cause dementia and a 28% reduction in the risk of ADRD, compared with levels above 130 mg/dL (3.4 mmol/L). For LDL-C levels below 55 mg/dL (1.4 mmol/L), there was an 18% risk reduction for both outcomes. Among those with LDL-C <70 mg/dL (<1.8 mmol/L), statin use was associated with a 13% reduction in all-cause dementia risk and a 12% decrease in ADRD risk compared with non-users.</p><p><strong>Conclusion: </strong>Low LDL-C levels (<70 mg/dL (<1.8 mmol/L)) are significantly associated with a reduced risk of dementia, including ADRD, with statin therapy providing additional protective effects. These findings support the necessity of targeted lipid management as a preventive strategy against dementia, indicating the importance of personalised treatment approaches.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764173","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":"MOG antibody non-P42 epitope is associated with a higher risk of relapse in paediatric MOGAD.","authors":"Aseel El Hajj, Anne Ruiz, Antoine Gavoille, Justine Couturier, Pascale Giraudon, Lakhdar Benyahya, Lisa Malaise, Maxime Bigotte, Claire Benetollo, Gaetan Amorim, Julia Roux, Carole Leroy, Ann-Kathrin Kogel, Ilya Ayzenberg, Friedemann Paul, Sudarshini Ramanathan, Russell C Dale, Kumaran Deiva, Fabienne Brilot, Romain Marignier","doi":"10.1136/jnnp-2024-335579","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335579","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers for predicting myelin oligodendrocyte glycoprotein antibody (Ab)-associated disease (MOGAD) clinical course are still missing. Binding capacity to a mutant MOG protein variant (MOG-P42S; non-P42) was shown to correlate with an increased relapse risk in adult patients.The objective of our study was to assess the frequency of binding to the non-P42 MOG variant in a cohort of paediatric MOGAD and to investigate its association with specific clinical profiles and disease course.</p><p><strong>Methods: </strong>We included children with MOG-Ab seropositive samples collected after their first demyelinating episode from five different centres. We performed live cell-based assays with native full-length MOG (MOG-FL) and mutant MOG-P42S and correlated the results with clinical data.</p><p><strong>Results: </strong>Of the 81 MOG-FL identified patients serum, 40 bound the non-P42 MOG. Non-P42 patients exhibited an earlier median age of onset (p=0.002). Phenotype distribution was different between groups (p=0.001), with non-P42 patients predominantly exhibiting acute disseminated encephalomyelitis phenotype. Notably, the non-P42 group was associated with a higher relapse rate (relative rate: 2.6 (95% CI 1.1 to 6.2), p=0.03), adjusted for clinical phenotype.</p><p><strong>Conclusion: </strong>Non-P42 is a promising biomarker for predicting relapse in paediatric MOGAD patients.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743160","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":"Muscle MRI quantifies disease progression in amyotrophic lateral sclerosis.","authors":"Uros Klickovic, Luca Zampedri, Nick Zafeiropoulos, Oliver J Ziff, Christopher Dj Sinclair, Stephen Wastling, Magdalena Dudziec, Jodie Allen, Karin Trimmel, Robin S Howard, Andrea Malaspina, Nikhil Sharma, Katie Cl Sidle, Sachit Shah, Christian Nasel, Tarek A Yousry, Linda Greensmith, Jasper M Morrow, John S Thornton, Pietro Fratta","doi":"10.1136/jnnp-2024-335571","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335571","url":null,"abstract":"<p><strong>Background and objectives: </strong>Quantitative and operator-independent biomarkers of disease progression are urgently needed in amyotrophic lateral sclerosis (ALS) research. We assess the potential of skeletal muscle MRI as a sensitive and reliable outcome measure for future ALS clinical trials.</p><p><strong>Methods: </strong>In this longitudinal cohort study, muscle MRI of head-neck, upper and lower limb regions, alongside clinical and functional assessments, were acquired at three time points over the individual maximum observation period (iMOP) of 1 year in 20 patients with ALS and 16 healthy controls. Quantitative MRI parameters cross-sectional area (CSA), volume (VOL), fat fraction, functional rest muscle area and water T2 (T_2m) were correlated with changes in clinical disease severity (functional rating scales and myometry).</p><p><strong>Results: </strong>Among 20 patients with ALS, 17 completed follow-up. Progressive muscle atrophy (CSA, VOL) was observed at hand (rs=0.66), head-neck (partial η²=0.47) and lower-limb level (thighs: η²=0.56, calves: η²=0.54) over iMOP. MRI changes correlated with leg muscle strength (knee extension: r=0.77; plantar flexion: r=0.78), hand grip strength (r=0.71) and functional rating scales (r=0.68).</p><p><strong>Interpretation: </strong>Our findings demonstrate the effectiveness of muscle MRI as a sensitive neuroimaging biomarker of disease progression in ALS, highlighting its potential application in clinical trials.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710338","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":"Prodromal phase of multiple sclerosis: evidence from sickness absence patterns before disease onset - a matched cohort study.","authors":"Ali Manouchehrinia, Feng Zhu, Jan Hillert, Kyla McKay, Yinshan Zhao, Ruth Ann Marrie, Helen Tremlett","doi":"10.1136/jnnp-2024-335279","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335279","url":null,"abstract":"<p><strong>Background: </strong>We aimed to investigate the prodromal phase of multiple sclerosis (MS) by investigating annual sickness absence rates before MS onset.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using Sweden's linked clinical and health administrative data. We identified MS cases via a validated algorithm using International Classification of Diseases (ICD) diagnostic codes for MS ('administrative cohort') or registration in the Swedish MS registry ('clinical cohort'). MS onset was defined as the first MS/demyelinating disease ICD code (administrative cohort) or, for the clinical cohort, MS symptom onset date, if earlier. Cases were matched with up to five controls from the general population with no MS/demyelinating disease history. Yearly sickness absence rates up to 18 years pre-MS onset were compared using negative binomial regression with generalised estimating equations.</p><p><strong>Results: </strong>The administrative/clinical cohorts comprised 8618/6361 MS cases and 43 072/31 776 controls. Sickness absence rate ratios were significantly elevated from 6 years before MS onset in the administrative cohort and 2 years before in the clinical cohort. The adjusted rate ratios peaked in the year pre-MS onset, reaching 2.59 (95% CI 2.40 to 2.79) in the administrative cohort and 1.19 (95% CI 1.06 to 1.34) in the clinical cohort. We also observed age-related and sex-related differences primarily in the year before MS onset, with males and older individuals exhibiting higher rate ratios.</p><p><strong>Conclusions: </strong>We observed a significant increase in sickness absence spells in individuals on the path to developing MS. Investigating sick leave patterns may provide a unique and broad perspective on the health trajectories of chronic conditions like MS.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710340","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":"Low natalizumab trough concentrations are associated with reduced seroconversion of the John Cunningham virus in natalizumab-treated patients with multiple sclerosis.","authors":"Liza M Y Gelissen, Alyssa A Toorop, Pien M Schipper, Elske Hoitsma, Esther M P E Zeinstra, Luuk C van Rooij, Caspar E P van Munster, Anke Vennegoor, Jop Mostert, Beatrijs Wokke, Nynke F Kalkers, Erwin L J Hoogervorst, Jeroen van Eijk, Christiaan M Roosendaal, Jolijn J Kragt, Marijke Eurelings, Jessie van Genugten, Jessica Nielsen, L G F Sinnige, Mark E Kloosterziel, Edo P J Arnoldus, Willem H Bouvy, Eva M Strijbis, Bob van Oosten, Brigit A De Jong, Bernard M J Uitdehaag, Birgit I Lissenberg-Witte, Floris C Loeff, Theo Rispens, Joep Killestein, Zoé L E van Kempen","doi":"10.1136/jnnp-2024-335761","DOIUrl":"https://doi.org/10.1136/jnnp-2024-335761","url":null,"abstract":"<p><strong>Background: </strong>Natalizumab is a highly effective drug for patients with relapsing-remitting multiple sclerosis (MS). A disadvantage of this treatment is the risk of progressive multifocal leukoencephalopathy in patients who are seropositive for the John Cunningham virus (JCV). JCV seroconversion rates increase under natalizumab treatment compared with non-natalizumab using controls. The aim of this study was to assess whether lower natalizumab trough concentrations are associated with reduced JCV seroconversion compared with higher natalizumab trough concentrations.</p><p><strong>Methods: </strong>Two overlapping cohorts of patients treated with intravenous natalizumab in the Netherlands were combined for this study. JCV seroconversion was assessed during periods of high (≥15 µg/mL) and low (<15 µg/mL) natalizumab trough concentrations. Low trough concentrations were mainly the result of trough concentration guided personalised extended interval dosing (EID). The seroconversion rates during high and low trough concentrations were compared using a generalised linear mixed model with a Poisson link function.</p><p><strong>Results: </strong>A total of 357 patients from 21 hospitals in the Netherlands were included. The annual seroconversion rate of 8.4% observed in patients during periods of high trough concentrations (n=226) was 2.32 times higher than the seroconversion rate of 4.8% in patients during periods of low trough concentrations (n=252) (95% CI=1.32 to 4.08, p=0.0035).</p><p><strong>Conclusions: </strong>The seroconversion rate observed in patients with MS with low trough concentrations was substantially lower compared with those with high trough concentrations during natalizumab treatment. This emphasises the importance of personalised EID, where intervals between infusions are prolonged to achieve lower natalizumab trough concentrations, to increase drug safety.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710334","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":"Predictors of relapse risk and treatment response in AQP4-IgG positive and seronegative NMOSD: A multicentre study.","authors":"Pakeeran Siriratnam, Paul Sanfilippo, Anneke van der Walt, Sifat Sharmin, Yi Chao Foong, Wei Zhen Yeh, Chao Zhu, Samia Joseph Khoury, Tunde Csepany, Barbara Willekens, Masoud Etemadifar, Serkan Ozakbas, Petra Nytrova, Ayse Altintas, Abdullah Al-Asmi, Bassem Yamout, Guy Laureys, Francesco Patti, Magdolna Simo, Andrea Surcinelli, Matteo Foschi, Pamela A McCombe, Raed Alroughani, José Luis Sánchez-Menoyo, Recai Turkoglu, Aysun Soysal, Jeanette Lechner Scott, Tomas Kalincik, Helmut Butzkueven, Vilija Jokubaitis, Saif Huda, Mastura Monif","doi":"10.1136/jnnp-2024-334090","DOIUrl":"10.1136/jnnp-2024-334090","url":null,"abstract":"<p><strong>Background: </strong>Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains less understood. This study aimed to evaluate the predictors of relapses and treatment responses in AQP4-IgG NMOSD and seronegative NMOSD.</p><p><strong>Methods: </strong>This was a multicentre, international, retrospective cohort study using the MSBase registry. Recurrent relapse risk was assessed using an Andersen-Gill model and risk of first relapse was evaluated using a Cox proportional hazards model. Covariates that putatively influence relapse risk included demographic factors, clinical characteristics and immunosuppressive therapies; the latter was assessed as a time-varying covariate.</p><p><strong>Results: </strong>A total of 398 patients (246 AQP4-IgG NMOSD and 152 seronegative NMOSD) were included. The AQP4-IgG NMOSD and seronegative NMOSD patients did not significantly differ by age at disease onset, ethnicity or annualised relapse rate. Both low-efficacy and high-efficacy immunosuppressive therapies were associated with significant reductions in recurrent relapse risk, with notably greater protection conferred by high-efficacy therapies in both AQP4-IgG NMOSD (HR 0.27, 95% CI 0.15 to 0.49, p<0.001) and seronegative NMOSD (HR 0.21, 95% CI 0.08 to 0.51, p<0.001). Longer disease duration (HR 0.97, 95% CI 0.95 to 0.99, p<0.001) and male sex (HR 0.52, 95% CI 0.34 to 0.84, p=0.007) were additional protective variables in reducing the recurrent relapse risk for the AQP4-IgG NMOSD group.</p><p><strong>Conclusion: </strong>Although further studies are needed to improve our understanding of seronegative NMOSD, our findings underscore the importance of aggressive treatment with high-efficacy immunotherapies in both NMOSD subtypes, regardless of serostatus.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"361-369"},"PeriodicalIF":8.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132955","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 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}