Journal of Neurology, Neurosurgery, and Psychiatry最新文献

{"title":"Smoking-attributable neurological health loss: age-specific burden and health disparities.","authors":"Yingjie Zhao, Lu Fei","doi":"10.1136/jnnp-2024-335536","DOIUrl":"10.1136/jnnp-2024-335536","url":null,"abstract":"<p><strong>Background: </strong>Smoking is a significant risk factor for neurological disorders, yet its global impact on these conditions remains underexplored.</p><p><strong>Methods: </strong>Using Global Burden of Diseases 2021 data, we analysed trends in age-standardised disability-adjusted life-years (DALYs) and deaths attributable to smoking from 1990 to 2021 for three neurological disorders: stroke, Alzheimer's disease and other dementias, and Multiple Sclerosis. Socioeconomic disparities were assessed using the lope index of inequality and the relative concentration index. Bayesian age-period-cohort models were employed to forecast smoking-attributable burden through 2050.</p><p><strong>Results: </strong>Between 1990 and 2021, annual smoking-attributable DALYs and death rates slightly declined by -1.93% and -1.92%, respectively, but absolute numbers continued to rise, from 26.10 million to 30.18 million DALYs and from 0.93 million to 1.15 million deaths. Older adults (aged 60 and above) experienced the greatest burden, contributing 58.15% of DALYs and 75.57% of deaths in 2021. Smoking-attributable stroke was increasingly concentrated in low sociodemographic index regions, whereas disparities in dementias and multiple sclerosis were more pronounced in socioeconomically advantaged regions, particularly for multiple sclerosis.</p><p><strong>Conclusions: </strong>This study identified an age-specific burden and widening disparities for neurological disorders attributable to smoking, with older adults disproportionately experiencing an escalating impact. Targeted prevention and equitable healthcare access tailored for older adults are critical to mitigating smoking-attributable neurological health loss.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"937-946"},"PeriodicalIF":7.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408681","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":"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":"960-965"},"PeriodicalIF":7.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505077/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifestyle factors associated with benign multiple sclerosis.","authors":"Jie Guo, Tomas Olsson, Jan Hillert, Lars Alfredsson, Anna Karin Hedström","doi":"10.1136/jnnp-2024-335464","DOIUrl":"10.1136/jnnp-2024-335464","url":null,"abstract":"<p><strong>Background: </strong>Benign multiple sclerosis (MS), characterised by minimal disability despite long disease duration, remains poorly understood in terms of its determinants and prognostic implications. While lifestyle factors have been implicated in modifying disease progression, their role in distinguishing benign and non-benign MS remains unclear.</p><p><strong>Methods: </strong>We conducted a comparative analysis of patients with benign (n=2040) and non-benign MS (n=4283) using data from Swedish nationwide case-control studies with long-term follow-up. Logistic regression models were used to analyse associations between a history of infectious mononucleosis (IM) and lifestyle factors (smoking, body mass index, fish consumption and sun exposure habits) and the likelihood of benign MS. Additionally, Cox regression was used to follow patients with benign MS from the 15-year mark onward, identifying factors associated with the transition to non-benign MS over time.</p><p><strong>Results: </strong>The odds of having benign MS were reduced in association with a history of IM (OR 0.54, 95% CI 0.45 to 0.65), adolescent overweight and obesity (OR 0.69, 95% CI 0.56 to 0.85 and 0.46, 95% CI 0.32 to 0.66, respectively) and infrequent fish consumption (OR 0.72, 95% CI 0.60 to 0.88). Similar associations were observed for the risk of transitioning from benign to non-benign MS over time.</p><p><strong>Conclusions: </strong>A history of IM and modifiable lifestyle factors significantly influence the probability of a benign disease course in MS. These findings underscore the potential for targeted lifestyle interventions to improve MS outcomes. Further research is needed to elucidate the mechanisms by which a past IM infection can continue to influence MS progression long after the initial infection.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"947-952"},"PeriodicalIF":7.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414456","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":"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":"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":"981-989"},"PeriodicalIF":7.5,"publicationDate":"2025-09-12","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":"Retinal imaging and tissue analysis for frontotemporal degeneration: recent advances and challenges for biomarker development.","authors":"Aaron T Zhao, Rohini M Nair, Edward B Lee, Katheryn A Q Cousins, David J Irwin, Benjamin J Kim","doi":"10.1136/jnnp-2024-335723","DOIUrl":"10.1136/jnnp-2024-335723","url":null,"abstract":"<p><p>Frontotemporal degeneration (FTD) is a group of neurodegenerative disorders affecting behaviour, language and executive functions. FTD is a common cause of early-onset dementia, but there are no FDA-approved treatments or established biomarkers for diagnosing and tracking these conditions, making early and accurate diagnosis challenging during life. Recent advances in retinal imaging, particularly through technologies like optical coherence tomography (OCT), have emerged as promising tools for identifying potential biomarkers for FTD and related neurodegenerative diseases. The retina, being an accessible extension of the central nervous system, has shown abnormalities that might serve as indicators of forms of FTD. Retinal imaging has revealed changes such as thinning of specific retinal layers that could correlate with molecular forms of FTD, Alzheimer's disease and other neurodegenerative diseases. These advances highlight the potential of retinal imaging to not only aid in diagnosis but also differentiate between various neurodegenerative conditions. Emerging data on retinal tissue analysis with immunohistochemistry and other techniques further support the potential of retinal biomarkers, though further studies are required to validate and refine these findings. Future advancements in retinal imaging technologies, along with longitudinal and autopsy-validated studies, are crucial for enhancing diagnostic capabilities and understanding FTD-related pathologies within the retina.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1012-1022"},"PeriodicalIF":7.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248331","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":"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":"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":"953-959"},"PeriodicalIF":7.5,"publicationDate":"2025-09-12","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":"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":"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":"975-980"},"PeriodicalIF":7.5,"publicationDate":"2025-09-12","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":"Characterising alexithymia in individuals with functional motor disorders: a cross-sectional analysis of the Italian Registry of Functional Motor Disorders.","authors":"Giovanni Ostuzzi, Christian Geroin, Chiara Gastaldon, Federico Tedeschi, Francesca Maria Clesi, Giacomo Trevisan, Giovanni Bidello, Giovanni Vita, Enrico Marcuzzo, Angela Sandri, Luigi M Romito, Roberto Eleopra, Lucia Tesolin, Ilaria Franch, Mario Zappia, Alessandra Nicoletti, Benedetta Demartini, Veronica Nisticò, Nicola Modugno, Enrica Olivola, Andrea Pilotto, Alessandro Padovani, Giovanni Defazio, Tommaso Ercoli, Martina Petracca, Rosa De Micco, Carlo Dallocchio, Marcello Esposito, Roberto Erro, Eleonora Del Prete, Francesco Amaddeo, Corrado Barbui, Michele Tinazzi","doi":"10.1136/jnnp-2024-334788","DOIUrl":"10.1136/jnnp-2024-334788","url":null,"abstract":"<p><strong>Background: </strong>Alexithymia, a personality trait characterised by difficulty in identifying and expressing emotions, may contribute to the onset and clinical presentation of functional motor disorders (FMDs), although this association remains underexplored.</p><p><strong>Methods: </strong>From the Italian Registry of FMDs, we selected individuals recruited between November 2011 and January 2023, diagnosed with FMD according to Gupta and Lang criteria and assessed for various neurological and psychological features with validated rating scales. The main statistical analysis included regression models using the Toronto Alexithymia Scale 20 items as an explanatory variable for a set of clinical measures, adjusting for sociodemographic factors and correcting for multiple testing.</p><p><strong>Results: </strong>In a cohort of 483 individuals, 20.7% had possible alexithymia and 31.5% had definite alexithymia. Higher levels of alexithymia were strongly associated with increased severity of depression (β=0.31, p<0.001), anxiety (β=0.32, p<0.001), general psychological distress (β=-0.27, p<0.001), fatigue (β=0.05, p<0.001) and pain (β=0.32, p<0.001) and moderately associated with a slower onset of FMD (β=0.02, p=0.003). Subscale analyses revealed that difficulties identifying feelings contributed most to these associations. No significant association was observed with motor symptom severity.</p><p><strong>Conclusions: </strong>Emotional processing difficulties of individuals with FMD and alexithymia might increase their vulnerability to mental health problems, pain and fatigue, possibly aggravating the overall prognosis. Further research is needed to elucidate the underlying mechanisms linking alexithymia to FMD and to explore the efficacy of interventions targeting emotional awareness and regulation in this population and to prevent long-term mental health burdens.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"990-997"},"PeriodicalIF":7.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441187","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":"Progression and life expectancy in primary lateral sclerosis.","authors":"David G Lester, Alexander G Thompson, Kevin Talbot, Martin R Turner","doi":"10.1136/jnnp-2025-336037","DOIUrl":"10.1136/jnnp-2025-336037","url":null,"abstract":"<p><strong>Objectives: </strong>To characterise the clinical characteristics and longitudinal outcomes in primary lateral sclerosis (PLS), including median survival from symptom onset and age at death.</p><p><strong>Methods: </strong>The authors retrospectively reviewed electronic health records of patients diagnosed with PLS referred to a specialised motor neuron disorders clinic from 2002 to 2024, analysed longitudinal Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) assessments using joint models and used Kaplan-Meier methods and life tables to calculate median survival and age at death compared with population-based values.</p><p><strong>Results: </strong>Of 52 patients, 34 (65%) were male, 41 (79%) first noted symptoms in the lower limbs and 10 (19%) in corticobulbar function. Median age of symptom onset was 53 years. The mean annual rate of functional decline was -1.92 ALSFRS-R points (95% CI -3.03 to -0.78), with equal highest rates of decline in fine and gross motor subscores. Five patients (10%) received gastrostomy and three (6%) non-invasive ventilation. Median survival from symptom onset was 23.1 years (22.7 to not reached), and median age at death was 79.5 years (77.8 to not reached) compared with a population-based reference mean of 81.9 years (81.1 to 82.8).</p><p><strong>Discussion: </strong>PLS may be commensurate with near-normal life expectancy. Significant disability arises from limb motor dysfunction, with a minority of patients requiring nutritional or respiratory support. This has important implications for counselling and trial design.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":" ","pages":"1008-1011"},"PeriodicalIF":7.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086259","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":"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":"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":"998-1007"},"PeriodicalIF":7.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505062/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}