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Paternal exposure to antiseizure medications and offspring outcomes: a systematic review 父亲接触抗癫痫药物与后代结局:系统性综述
IF 11 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-19 DOI: 10.1136/jnnp-2024-334077
Eliza Honybun, Genevieve Rayner, Charles B Malpas, Terence J O'Brien, Frank J Vajda, Piero Perucca, Emilio Perucca
Background Concerns have recently been raised about risks to the fetus resulting from paternal exposure to antiseizure medications (ASMs). To address these concerns, we conducted a systematic review of the literature to assess neurodevelopmental and anatomical outcomes in offspring born to fathers taking ASMs at the time of conception. Methods Electronic searches of MEDLINE, PsycINFO, and Embase were conducted to identify human studies published in English that reported on outcomes, comprising neurodevelopmental disorders, major congenital malformations, small-for-gestational age or low birth weight, in offspring of fathers taking ASMs at conception. Quality analysis of included studies was undertaken using the Newcastle-Ottawa Scale. A narrative synthesis was used to report study findings. Results Of 923 studies identified by the search and screened by title and abstract, 26 underwent full-text review and 10 met eligibility criteria. There was limited evidence available, but there appeared to be no clear evidence for an adverse impact of paternal ASM use on offspring outcomes. Few isolated adverse findings were not replicated by other investigations. Several methodological limitations prevented meta-analysis, including failure by most studies to report outcomes separately for each individual ASM, heterogeneity in measurement and outcome reporting, and small numbers of monotherapy exposures. Conclusions Although there were limited data available, this systematic review provides reassuring evidence that paternal exposure to ASMs at conception is unlikely to pose any major risk of adverse outcomes for the offspring. Further research is needed to examine the relationship between preconception ASM use in males and offspring outcomes at birth and postnatally. Data are available upon reasonable request.
背景 最近,人们开始关注父亲接触抗癫痫药物(ASM)对胎儿造成的风险。为了解决这些问题,我们对文献进行了系统性回顾,以评估父亲在受孕时服用 ASMs 对胎儿神经发育和解剖学结果的影响。方法 通过对 MEDLINE、PsycINFO 和 Embase 进行电子检索,找出以英文发表的人类研究,这些研究报告了父亲在受孕时服用 ASMs 的后代的神经发育障碍、主要先天畸形、小胎龄或低出生体重等结果。采用纽卡斯尔-渥太华量表对纳入的研究进行了质量分析。采用叙事综合法报告研究结果。结果 在检索并通过标题和摘要筛选出的 923 项研究中,26 项进行了全文审阅,10 项符合资格标准。现有证据有限,但似乎没有明确的证据表明父亲使用 ASM 对后代的结果有不利影响。少数孤立的不利结果没有被其他调查所重复。一些方法上的局限性妨碍了荟萃分析,包括大多数研究未能单独报告每种 ASM 的结果、测量和结果报告的异质性以及单一疗法暴露的数量较少。结论 虽然可用数据有限,但本系统综述提供了令人欣慰的证据,即父亲在受孕时接触 ASM 不太可能给后代带来不良后果的任何重大风险。需要进一步研究男性在受孕前使用 ASM 与后代出生时和出生后结果之间的关系。如有合理要求,可提供相关数据。
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引用次数: 0
Paternal exposure to antiseizure medications and offspring outcomes 父亲接触抗癫痫药物与后代的结局
IF 11 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-19 DOI: 10.1136/jnnp-2024-334474
Torbjörn Tomson
Is there evidence to support restrictions in the use of valproate in male patients? This issue is addressed in a JNNP systematic review presented in the paper by Honybun et al. 1 The review provides a comprehensive assessment of different teratogenic outcomes in offspring associated with paternal exposure to antiseizure medications, and the results are reassuring. In 2014, the European Medicines Agency (EMA) issued contraindications for the use of valproate during pregnancy and imposed restrictions for its use in girls and female patients due to overwhelming evidence of its teratogenic risks. Restrictions were clearly justified, despite valproate being the most effective medication for some types of generalised epilepsies. In November 2023, the UK Medicines and Healthcare products Regulatory …
是否有证据支持限制男性患者使用丙戊酸钠?Honybun等人在JNNP上发表的一篇系统综述1探讨了这一问题。该综述全面评估了与父亲暴露于抗癫痫药物相关的后代不同致畸结果,结果令人欣慰。2014 年,由于有大量证据表明丙戊酸钠有致畸风险,欧洲药品管理局(EMA)发布了妊娠期使用丙戊酸钠的禁忌症,并限制其在女孩和女性患者中的使用。尽管丙戊酸钠是治疗某些类型全身性癫痫的最有效药物,但限制使用丙戊酸钠显然是合理的。2023 年 11 月,英国药品和保健品监管局(UK Medicines and Healthcare Products Regulatory ...
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引用次数: 0
Is speech function lateralised in the basal ganglia? Evidence from de novo Parkinson’s disease 基底神经节的言语功能是否偏向一侧?新帕金森病的证据
IF 11 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-17 DOI: 10.1136/jnnp-2024-334297
Jan Rusz, Petr Dusek, Tereza Tykalova, Michal Novotny, Vojtech Illner, Michal Simek, Tomas Kouba, Petr Kryze, David Zogala, Evzen Ruzicka, Mário Sousa, Adriana Jorge, Tobias Nef, Paul Krack
Background Research on the possible influence of lateralised basal ganglia dysfunction on speech in Parkinson’s disease is scarce. This study aimed to compare speech in de-novo, drug-naive patients with Parkinson’s disease (PD) with asymmetric nigral dopaminergic dysfunction, predominantly in either the right or left hemisphere. Methods Acoustic analyses of reading passages were performed. Asymmetry of nigral dysfunction was defined using dopamine transporter-single-photon emission CT (DAT-SPECT). Results From a total of 135 de novo patients with PD assessed, 47 patients had a lower right and 36 lower left DAT availability in putamen based on DAT-SPECT. Patients with PD with lower left DAT availability had higher dysarthria severity via composite dysarthria index compared with patients with lower right DAT availability (p=0.01). Conclusion Our data support the crucial role of DAT availability in the left putamen in speech. This finding might provide important clues for managing speech following deep brain stimulation.
背景有关侧向基底节功能障碍对帕金森病患者言语可能产生的影响的研究很少。本研究旨在比较帕金森病(PD)非对称性黑质多巴胺能功能障碍(主要发生在右半球或左半球)的未服药帕金森病患者的言语能力。方法 对阅读段落进行声学分析。使用多巴胺转运体-单光子发射CT(DAT-SPECT)确定黑质功能障碍的不对称性。结果 在接受评估的135名新发型帕金森病患者中,根据DAT-SPECT结果,47名患者的右侧和36名患者的左侧DAT含量较低。与右侧DAT可用性较低的患者相比,左侧DAT可用性较低的帕金森病患者通过综合构音障碍指数得出的构音障碍严重程度更高(P=0.01)。结论 我们的数据支持左侧大脑丘脑中的 DAT 在言语中的关键作用。这一发现可能为深部脑刺激后的言语管理提供重要线索。
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引用次数: 0
Resective epilepsy surgery and its impact on depression in adults: a systematic review, meta-analysis, and implications for future research. 切除性癫痫手术及其对成人抑郁症的影响:系统综述、荟萃分析及对未来研究的启示。
IF 8.7 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-17 DOI: 10.1136/jnnp-2023-333073
Natalia Hernandez Poblete, Florian Gay, Francesco Salvo, Jean-Arthur Micoulaud-Franchi, Thomas Bienvenu, Julien Coelho, Jerome Aupy

Background: How epilepsy surgery influences the bidirectional relationship of epilepsy and depression remains poorly defined.

Method: For a better understanding of this question, we conducted a systematic review and meta-analysis of risk ratio on depression prevalence before and after epilepsy surgery, using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Three databases were comprehensively screened for all studies assessing depression before and after resective surgery in adult epileptic patients until 8 October 2022. Studies were included if depression was assessed before and after epilepsy surgery regardless of the time of follow-up. A total of 1917 studies were screened for eligibility and 91 full-texts up for inclusion; 35 studies were finally included, 25 studies and 2563 patients were included in main meta-analysis and 10 for exploratory analysis. Risk of bias was assessed using Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) from Cochrane. To derive the pooled depression rates before and after surgery, a meta-analysis with inversed-variance was performed using random-effects logistic models with Peto's correction and a 95% CI. Heterogeneity was assessed with Cochran's Q-test along with its derived measure of inconsistency I2.

Results: Overall, the depression rates before and after resective epilepsy surgery were 0.70 (0.53 to 0.91) 95% CI, suggesting that the rate of depression at last follow-up evaluation tends to decrease after Resective Epilepsy Surgery (RES). Subgroup analysis suggest a positive long-term effect appears with a significant lower rates of depression already 6 months (0.61 (0.38 to 0.98)), after surgery which is maintained over time after 1 year (0.53 (0.31 to 0.90)), and after 2 years (0.62 (0.42 to 0.92)).

Conclusion: This important finding should be taken in consideration before resective surgery for drug-resistant epilepsies. However, prospective studies should be conducted to characterise which patient, at the individual level, might be at risk of de novo or worsening of depression.

Prospero registration number: CRD42022355386.

背景:癫痫手术如何影响癫痫和抑郁症的双向关系?癫痫手术如何影响癫痫与抑郁的双向关系,目前尚不明确:为了更好地理解这一问题,我们采用系统综述和荟萃分析首选报告项目指南,对癫痫手术前后抑郁症患病率的风险比进行了系统综述和荟萃分析。截至 2022 年 10 月 8 日,我们在三个数据库中全面筛选了所有评估成年癫痫患者切除手术前后抑郁情况的研究。无论随访时间长短,只要在癫痫手术前后对抑郁进行了评估,均纳入研究。共筛选出1917项研究符合条件,91项全文被纳入;最终纳入35项研究,25项研究和2563名患者被纳入主要荟萃分析,10项研究被纳入探索性分析。偏倚风险采用 Cochrane 的 "非随机干预研究中的偏倚风险"(ROBINS-I)进行评估。为了得出手术前后的合并抑郁率,我们使用随机效应逻辑模型进行了反方差荟萃分析,并使用了 Peto's 校正和 95% CI。异质性通过科克伦 Q 检验及其衍生的不一致性指标 I2 进行评估:总体而言,切除性癫痫手术前后的抑郁率为0.70(0.53至0.91)95% CI,表明切除性癫痫手术(RES)后,最后一次随访评估时的抑郁率呈下降趋势。亚组分析表明,术后6个月(0.61(0.38至0.98))、术后1年(0.53(0.31至0.90))和术后2年(0.62(0.42至0.92))的抑郁率显著降低,从而产生了积极的长期效应:在对耐药性癫痫进行切除手术之前,应考虑到这一重要发现。然而,还应该开展前瞻性研究,以确定哪些患者在个体水平上可能面临抑郁症复发或恶化的风险:CRD42022355386。
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引用次数: 0
Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world. 重新定义偏头痛的预防:使用抗 CGRP 单克隆抗体进行早期治疗可增强真实世界中的反应。
IF 8.7 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-17 DOI: 10.1136/jnnp-2023-333295
Edoardo Caronna, Victor José Gallardo, Gabriella Egeo, Manuel Millán Vázquez, Candela Nieves Castellanos, Javier A Membrilla, Gloria Vaghi, Joana Rodríguez-Montolio, Neus Fabregat Fabra, Francisco Sánchez-Caballero, Alex Jaimes Sánchez, Albert Muñoz-Vendrell, Renato Oliveira, Gabriel Gárate, Yésica González-Osorio, Daniel Guisado-Alonso, Raffaele Ornello, Cem Thunstedt, Iris Fernández-Lázaro, Marta Torres-Ferrús, Alicia Alpuente, Paola Torelli, Cinzia Aurilia, Raquel Lamas Pére, Maria José Ruiz Castrillo, Roberto De Icco, Grazia Sances, Sarah Broadhurst, Hui Ching Ong, Andrea Gómez García, Sergio Campoy, Jordi Sanahuja, Gonçalo Cabral, Isabel Beltrán Blasco, Marta Waliszewska-Prosół, Liliana Pereira, Almudena Layos-Romero, Isabel Luzeiro, Laura Dorado, María Rocio Álvarez Escudero, Arne May, Alba López-Bravo, Isabel Pavão Martins, Christina Sundal, Pablo Irimia, Alberto Lozano Ros, Ana Beatriz Gago-Veiga, Fernando Velasco Juanes, Ruth Ruscheweyh, Simona Sacco, Elisa Cuadrado-Godia, David García-Azorín, Julio Pascual, Raquel Gil-Gouveia, Mariano Huerta-Villanueva, Jaime Rodriguez-Vico, Javier Viguera Romero, Victor Obach, Sonia Santos-Lasaosa, Mona Ghadiri-Sani, Cristina Tassorelli, Javier Díaz-de-Terán, Samuel Díaz Insa, Carmen González Oria, Piero Barbanti, Patricia Pozo-Rosich

Background: Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months.

Methods: European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response.

Results: Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models.

Conclusions: This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.

背景:抗 CGRP 单克隆抗体(anti-CGRP MAbs)是已获批准且可用来预防偏头痛的治疗方法。患者的反应不尽相同,许多国家的报销政策阻碍了对可能有反应的患者的治疗。本研究旨在调查与抗CGRP MAbs 6个月后良好和卓越反应相关的临床因素:欧洲多中心、前瞻性、真实世界研究,包括自2018年3月以来接受抗CGRP MAbs治疗的高频发作性或慢性偏头痛(CM)患者。我们将良好和卓越反应分别定义为6个月时每月头痛天数(MHD)减少≥50%和≥75%。采用广义混合效应回归模型(GLMM)确定与治疗反应独立相关的变量:在纳入的 5818 名患者中,82.3% 为女性,年龄中位数为 48.0(40.0-55.0)岁。基线时,MHD的中位数为20.0(14.0-28.0)天/月,72.2%的患者被诊断为CM。6 个月时(n=4963),56.5% 的患者(2804/4963)反应良好,26.7% 的患者(1324/4963)反应极佳。在 GLMM 模型中,年龄较大(1.08(95% CI 1.02 至 1.15),p=0.016)、存在单侧疼痛(1.39(95% CI 1.21 至 1.60),p结论:这是针对接受抗CGRP MAbs治疗的偏头痛患者进行的最大规模的真实世界研究。它提供的证据表明,基线偏头痛频率越高、残疾程度越严重,对抗CGRP MAbs产生反应的可能性就越小,这让医生和政策制定者了解到需要尽早治疗,以提供最佳的治疗成功机会。
{"title":"Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world.","authors":"Edoardo Caronna, Victor José Gallardo, Gabriella Egeo, Manuel Millán Vázquez, Candela Nieves Castellanos, Javier A Membrilla, Gloria Vaghi, Joana Rodríguez-Montolio, Neus Fabregat Fabra, Francisco Sánchez-Caballero, Alex Jaimes Sánchez, Albert Muñoz-Vendrell, Renato Oliveira, Gabriel Gárate, Yésica González-Osorio, Daniel Guisado-Alonso, Raffaele Ornello, Cem Thunstedt, Iris Fernández-Lázaro, Marta Torres-Ferrús, Alicia Alpuente, Paola Torelli, Cinzia Aurilia, Raquel Lamas Pére, Maria José Ruiz Castrillo, Roberto De Icco, Grazia Sances, Sarah Broadhurst, Hui Ching Ong, Andrea Gómez García, Sergio Campoy, Jordi Sanahuja, Gonçalo Cabral, Isabel Beltrán Blasco, Marta Waliszewska-Prosół, Liliana Pereira, Almudena Layos-Romero, Isabel Luzeiro, Laura Dorado, María Rocio Álvarez Escudero, Arne May, Alba López-Bravo, Isabel Pavão Martins, Christina Sundal, Pablo Irimia, Alberto Lozano Ros, Ana Beatriz Gago-Veiga, Fernando Velasco Juanes, Ruth Ruscheweyh, Simona Sacco, Elisa Cuadrado-Godia, David García-Azorín, Julio Pascual, Raquel Gil-Gouveia, Mariano Huerta-Villanueva, Jaime Rodriguez-Vico, Javier Viguera Romero, Victor Obach, Sonia Santos-Lasaosa, Mona Ghadiri-Sani, Cristina Tassorelli, Javier Díaz-de-Terán, Samuel Díaz Insa, Carmen González Oria, Piero Barbanti, Patricia Pozo-Rosich","doi":"10.1136/jnnp-2023-333295","DOIUrl":"10.1136/jnnp-2023-333295","url":null,"abstract":"<p><strong>Background: </strong>Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months.</p><p><strong>Methods: </strong>European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response.</p><p><strong>Results: </strong>Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models.</p><p><strong>Conclusions: </strong>This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081540","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}
引用次数: 0
Epidemiology of myasthenia gravis in Denmark, Finland and Sweden: a population-based observational study. 丹麦、芬兰和瑞典的重症肌无力流行病学:一项基于人口的观察研究。
IF 8.7 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-17 DOI: 10.1136/jnnp-2023-333097
John Vissing, Sari Atula, Mari Savolainen, Juha Mehtälä, Laila Mehkri, Tina Bech Olesen, Tero Ylisaukko-Oja, Ingrid Lindberg-Schager, Fredrik Berggren, Fredrik Piehl

Background: Incidence and prevalence rates of myasthenia gravis (MG) vary considerably across studies, and mortality risk is rarely addressed. We examined the prevalence and incidence rates, mortality and factors associated with mortality with MG.

Method: This was a registry linkage study based on nationwide health and administrative registries of Denmark, Finland and Sweden (populations of 5.9, 5.6 and 10.5 million, respectively). Patients with MG were identified based on International Classification of Diseases codes from inpatient and outpatient specialised care registries. Yearly prevalence, incidence and mortality rates in relation to the total background population were calculated from 2000 to 2020 (study period). The causes of death and factors associated with mortality were addressed separately.

Results: The overall incidence of MG was 1.34 (95% CI 1.27 to 1.41), 1.68 (95% CI 1.60 to 1.75) and 1.62 (95% CI 1.56 to 1.68) per 100 000, and the overall prevalence per 100 000 was 18.56 (95% CI 18.31 to 18.81), 20.89 (95% CI 20.62 to 21.16) and 23.42 (95% CI 23.21 to 23.64) in Denmark, Finland and Sweden, respectively. The overall standardised mortality ratio (SMR) was 1.32 (95% CI 1.23 to 1.42) among patients with MG in Denmark, 1.23 (95% CI 1.15 to 1.33) in Finland, and 1.20 (95% CI 1.14 to 1.26) in Sweden, with higher SMR observed in women than men. Annual incidence and prevalence increased over time, whereas the SMR remained stable. The most common causes of death were MG, chronic ischaemic heart disease and acute myocardial infarction.

Conclusions: This population-based study from three Nordic countries highlights the need for improved care of patients with MG, especially young women.

背景:肌无力(MG)的发病率和患病率在不同的研究中差异很大,而且很少涉及死亡风险。我们研究了重症肌无力的患病率和发病率、死亡率以及与死亡率相关的因素:这是一项基于丹麦、芬兰和瑞典(人口分别为 590 万、560 万和 1050 万)全国健康和行政登记处的登记处链接研究。根据住院病人和门诊病人专科登记处的国际疾病分类代码,确定了MG患者。计算了 2000 年至 2020 年(研究期间)与背景总人口相关的年患病率、发病率和死亡率。研究分别探讨了死亡原因和与死亡相关的因素:丹麦、芬兰和瑞典的 MG 总发病率分别为每 10 万人 1.34 例(95% CI 1.27 至 1.41 例)、1.68 例(95% CI 1.60 至 1.75 例)和 1.62 例(95% CI 1.56 至 1.68 例),总患病率分别为每 10 万人 18.56 例(95% CI 18.31 至 18.81 例)、20.89 例(95% CI 20.62 至 21.16 例)和 23.42 例(95% CI 23.21 至 23.64 例)。在丹麦、芬兰和瑞典,MG 患者的总标准化死亡率(SMR)分别为 1.32(95% CI 1.23 至 1.42)、1.23(95% CI 1.15 至 1.33)和 1.20(95% CI 1.14 至 1.26),女性患者的 SMR 高于男性。随着时间的推移,每年的发病率和流行率都在增加,而SMR则保持稳定。最常见的死亡原因是MG、慢性缺血性心脏病和急性心肌梗死:这项基于三个北欧国家人口的研究强调,有必要改善对 MG 患者,尤其是年轻女性患者的护理。
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引用次数: 0
Neuropsychiatric symptoms in cognitive decline and Alzheimer’s disease: biomarker discovery using plasma proteomics 认知能力下降和阿尔茨海默病的神经精神症状:利用血浆蛋白质组学发现生物标志物
IF 11 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-17 DOI: 10.1136/jnnp-2024-333819
Miriam Rabl, Christopher Clark, Loïc Dayon, Julius Popp
Background and objectives Neuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer’s disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of NPS are available yet. This study aimed to identify plasma proteins that may serve as biomarkers for NPS and NPS-related clinical disease progression. Methods A panel of 190 plasma proteins was quantified using Luminex xMAP in the Alzheimer’s Disease Neuroimaging Initiative cohort. NPS and cognitive performance were assessed at baseline and after 1 and 2 years. Logistic regression, receiver operating characteristic analysis and cross-validation were used to address the relations of interest. Results A total of 507 participants with mild cognitive impairment (n=396) or mild AD dementia (n=111) were considered. Selected plasma proteins improved the prediction of NPS (area under the curve (AUC) from 0.61 to 0.76, p<0.001) and future NPS (AUC from 0.63 to 0.80, p<0.001) when added to a reference model. Distinct protein panels were identified for single symptoms. Among the selected proteins, ANGT, CCL1 and IL3 were associated with NPS at all three time points while CCL1, serum glutamic oxaloacetic transaminase and complement factor H were also associated with cognitive decline. The associations were independent of the presence of cerebral AD pathology as assessed using cerebrospinal fluid biomarkers. Conclusions Plasma proteins are associated with NPS and improve prediction of future NPS. Data are available in a public, open access repository. The data that support the findings of this study are accessible through the ADNI database (). Interested researchers can request access through the ADNI website. The data used in the present study were downloaded in December 2022.
背景和目的 神经精神症状(NPS)在患有认知障碍和阿尔茨海默病(AD)的老年人中很常见。目前尚无生物标志物来检测相关病理或预测 NPS 的临床演变。本研究旨在确定可作为 NPS 和 NPS 相关临床疾病进展生物标志物的血浆蛋白。方法 使用 Luminex xMAP 对阿尔茨海默病神经影像学倡议队列中的 190 种血浆蛋白进行量化。在基线及 1 年和 2 年后对 NPS 和认知能力进行评估。采用逻辑回归、接受者操作特征分析和交叉验证来解决相关关系。结果 共有507名轻度认知障碍(396人)或轻度AD痴呆(111人)患者接受了研究。选定的血浆蛋白提高了对NPS的预测(曲线下面积(AUC)从0.61提高到0.76,p)。感兴趣的研究人员可通过 ADNI 网站申请访问。本研究使用的数据于 2022 年 12 月下载。
{"title":"Neuropsychiatric symptoms in cognitive decline and Alzheimer’s disease: biomarker discovery using plasma proteomics","authors":"Miriam Rabl, Christopher Clark, Loïc Dayon, Julius Popp","doi":"10.1136/jnnp-2024-333819","DOIUrl":"https://doi.org/10.1136/jnnp-2024-333819","url":null,"abstract":"Background and objectives Neuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer’s disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of NPS are available yet. This study aimed to identify plasma proteins that may serve as biomarkers for NPS and NPS-related clinical disease progression. Methods A panel of 190 plasma proteins was quantified using Luminex xMAP in the Alzheimer’s Disease Neuroimaging Initiative cohort. NPS and cognitive performance were assessed at baseline and after 1 and 2 years. Logistic regression, receiver operating characteristic analysis and cross-validation were used to address the relations of interest. Results A total of 507 participants with mild cognitive impairment (n=396) or mild AD dementia (n=111) were considered. Selected plasma proteins improved the prediction of NPS (area under the curve (AUC) from 0.61 to 0.76, p<0.001) and future NPS (AUC from 0.63 to 0.80, p<0.001) when added to a reference model. Distinct protein panels were identified for single symptoms. Among the selected proteins, ANGT, CCL1 and IL3 were associated with NPS at all three time points while CCL1, serum glutamic oxaloacetic transaminase and complement factor H were also associated with cognitive decline. The associations were independent of the presence of cerebral AD pathology as assessed using cerebrospinal fluid biomarkers. Conclusions Plasma proteins are associated with NPS and improve prediction of future NPS. Data are available in a public, open access repository. The data that support the findings of this study are accessible through the ADNI database (<http://adni.loni.usc.edu>). Interested researchers can request access through the ADNI website. The data used in the present study were downloaded in December 2022.","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249590","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}
引用次数: 0
Venous thromboembolism risk in amyotrophic lateral sclerosis: a hospital record-linkage study. 肌萎缩侧索硬化症的静脉血栓栓塞风险:一项医院记录关联研究。
IF 8.7 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-17 DOI: 10.1136/jnnp-2024-333399
Raph Goldacre, Michael Trubshaw, Eva J A Morris, Kevin Talbot, Michael J Goldacre, Alexander Guy Thompson, Martin R Turner

Background: Venous thromboembolism (VTE) can occur in amyotrophic lateral sclerosis (ALS) and pulmonary embolism causes death in a minority of cases. The benefits of preventing VTE must be weighed against the risks. An accurate estimate of the incidence of VTE in ALS is crucial to assessing this balance.

Methods: This retrospective record-linkage cohort study derived data from the Hospital Episode Statistics database, covering admissions to England's hospitals from 1 April 2003 to 31 December 2019 and included 21 163 patients with ALS and 17 425 337 controls. Follow-up began at index admission and ended at VTE admission, death or 2 years (whichever came sooner). Adjusted HRs (aHRs) for VTE were calculated, controlling for confounders.

Results: The incidence of VTE in the ALS cohort was 18.8/1000 person-years. The relative risk of VTE in ALS was significantly greater than in controls (aHR 2.7, 95% CI 2.4 to 3.0). The relative risk of VTE in patients with ALS under 65 years was five times higher than controls (aHR 5.34, 95% CI 4.6 to 6.2), and higher than that of patients over 65 years compared with controls (aHR 1.86, 95% CI 1.62 to 2.12).

Conclusions: Patients with ALS are at a higher risk of developing VTE, but this is similar in magnitude to that reported in other chronic neurological conditions associated with immobility, such as multiple sclerosis, which do not routinely receive VTE prophylaxis. Those with ALS below the median age of symptom onset have a notably higher relative risk. A reappraisal of the case for routine antithrombotic therapy in those diagnosed with ALS now requires a randomised controlled trial.

背景:肌萎缩性脊髓侧索硬化症(ALS)患者可能会发生静脉血栓栓塞症(VTE),肺栓塞会导致少数患者死亡。必须权衡预防 VTE 的益处和风险。准确估计 ALS VTE 的发病率对于评估这种平衡至关重要:这项回顾性记录关联队列研究的数据来自医院病例统计数据库,涵盖2003年4月1日至2019年12月31日期间英格兰医院的入院病例,包括21163名ALS患者和17 425 337名对照者。随访从索引入院开始,到VTE入院、死亡或2年(以时间在前者为准)结束。在控制了混杂因素后,计算了VTE的调整HRs(aHRs):结果:ALS队列中VTE的发病率为18.8/1000人年。ALS 患者发生 VTE 的相对风险明显高于对照组(aHR 2.7,95% CI 2.4 至 3.0)。65岁以下ALS患者发生VTE的相对风险是对照组的5倍(aHR为5.34,95% CI为4.6至6.2),高于65岁以上患者与对照组相比的相对风险(aHR为1.86,95% CI为1.62至2.12):ALS患者罹患VTE的风险较高,但其风险程度与多发性硬化症等其他与行动不便有关的慢性神经系统疾病的风险相似,这些疾病的患者并不常规接受VTE预防治疗。发病年龄低于中位数的 ALS 患者的相对风险明显更高。现在需要进行随机对照试验,重新评估对确诊为 ALS 的患者进行常规抗血栓治疗的理由。
{"title":"Venous thromboembolism risk in amyotrophic lateral sclerosis: a hospital record-linkage study.","authors":"Raph Goldacre, Michael Trubshaw, Eva J A Morris, Kevin Talbot, Michael J Goldacre, Alexander Guy Thompson, Martin R Turner","doi":"10.1136/jnnp-2024-333399","DOIUrl":"10.1136/jnnp-2024-333399","url":null,"abstract":"<p><strong>Background: </strong>Venous thromboembolism (VTE) can occur in amyotrophic lateral sclerosis (ALS) and pulmonary embolism causes death in a minority of cases. The benefits of preventing VTE must be weighed against the risks. An accurate estimate of the incidence of VTE in ALS is crucial to assessing this balance.</p><p><strong>Methods: </strong>This retrospective record-linkage cohort study derived data from the Hospital Episode Statistics database, covering admissions to England's hospitals from 1 April 2003 to 31 December 2019 and included 21 163 patients with ALS and 17 425 337 controls. Follow-up began at index admission and ended at VTE admission, death or 2 years (whichever came sooner). Adjusted HRs (aHRs) for VTE were calculated, controlling for confounders.</p><p><strong>Results: </strong>The incidence of VTE in the ALS cohort was 18.8/1000 person-years. The relative risk of VTE in ALS was significantly greater than in controls (aHR 2.7, 95% CI 2.4 to 3.0). The relative risk of VTE in patients with ALS under 65 years was five times higher than controls (aHR 5.34, 95% CI 4.6 to 6.2), and higher than that of patients over 65 years compared with controls (aHR 1.86, 95% CI 1.62 to 2.12).</p><p><strong>Conclusions: </strong>Patients with ALS are at a higher risk of developing VTE, but this is similar in magnitude to that reported in other chronic neurological conditions associated with immobility, such as multiple sclerosis, which do not routinely receive VTE prophylaxis. Those with ALS below the median age of symptom onset have a notably higher relative risk. A reappraisal of the case for routine antithrombotic therapy in those diagnosed with ALS now requires a randomised controlled trial.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318510","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}
引用次数: 0
Imaging endolymphatic space of the inner ear in vestibular migraine 前庭性偏头痛的内耳内淋巴间隙成像
IF 11 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-13 DOI: 10.1136/jnnp-2024-334419
Valerie Kirsch, Rainer Boegle, Johannes Gerb, Emilie Kierig, Birgit B Ertl-Wagner, Sandra Becker-Bense, Thomas Brandt, Marianne Dieterich
Background Vestibular migraine (VM), the most frequent episodic vertigo, is difficult to distinguish from Ménière’s disease (MD) because reliable biomarkers are missing. The classical proof of MD was an endolymphatic hydrops (EH). However, a few intravenous gadolinium-enhanced MRI studies of the inner ear ( i MRI) also revealed an EH in VM. The major questions were the frequency and distribution characteristics of EH in VM for diagnostic use. Methods In a prospective case-control study of 200 participants, 75 patients with VM (49 females; mean age 46 years) and 75 with MD (36 females; mean age 55 years), according to the Bárány and International Headache Society, and 50 age-matched participants with normal vestibulocochlear testing (HP), were enrolled. Analyses of i MRI of the endolymphatic space included volumetric quantification, stepwise regression, correlation with neurotological parameters and support vector machine classification. Results EH was maximal in MD (80%), less in VM (32%) and minimal in HP (22%). EH was milder in VM (mean grade 0.3) compared with MD (mean grade 1.3). The intralabyrinthine distribution was preferably found in the vestibulum in VM, but mainly in the cochlea in MD. There was no interaural lateralisation of EH in VM but in the affected ear in MD. The grade of EH in the vestibulum was correlated in both conditions with the frequency and duration of the attacks. Conclusion Three features of the i MRI evaluation were most supportive for the diagnosis of VM at group and individual levels: (1) the bilateral manifestation, (2) the low-grade EH and (3) the intraaural distribution. All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.
背景前庭性偏头痛(VM)是最常见的发作性眩晕,由于缺乏可靠的生物标志物,很难与梅尼埃病(MD)区分开来。梅尼埃病的经典证据是内淋巴水肿(EH)。然而,一些静脉注射钆增强的内耳核磁共振成像(i MRI)研究也发现了 VM 中的 EH。主要问题是用于诊断的 VM EH 的频率和分布特征。方法 在一项有 200 名参与者参加的前瞻性病例对照研究中,根据巴拉尼和国际头痛协会的标准,纳入了 75 名 VM 患者(49 名女性;平均年龄 46 岁)和 75 名 MD 患者(36 名女性;平均年龄 55 岁),以及 50 名年龄匹配且前庭耳蜗测试(HP)正常的参与者。内淋巴空间 i MRI 分析包括体积量化、逐步回归、与神经学参数的相关性和支持向量机分类。结果 EH 在 MD 中最大(80%),在 VM 中较小(32%),在 HP 中最小(22%)。与 MD(平均 1.3 级)相比,VM 的 EH 较轻(平均 0.3 级)。在 VM 中,迷宫内的分布主要在前庭,而在 MD 中则主要在耳蜗。在 VM 中,EH 没有耳间侧向分布,但在 MD 中,EH 则分布在患耳。在这两种情况下,前庭中 EH 的等级与发作频率和持续时间相关。结论 i MRI 评估的三个特征最能支持 VM 的集体和个体诊断:(1) 双侧表现;(2) 低级别 EH;(3) 耳内分布。与该研究相关的所有数据均包含在文章中或作为补充信息上传。不适用。
{"title":"Imaging endolymphatic space of the inner ear in vestibular migraine","authors":"Valerie Kirsch, Rainer Boegle, Johannes Gerb, Emilie Kierig, Birgit B Ertl-Wagner, Sandra Becker-Bense, Thomas Brandt, Marianne Dieterich","doi":"10.1136/jnnp-2024-334419","DOIUrl":"https://doi.org/10.1136/jnnp-2024-334419","url":null,"abstract":"Background Vestibular migraine (VM), the most frequent episodic vertigo, is difficult to distinguish from Ménière’s disease (MD) because reliable biomarkers are missing. The classical proof of MD was an endolymphatic hydrops (EH). However, a few intravenous gadolinium-enhanced MRI studies of the inner ear ( i MRI) also revealed an EH in VM. The major questions were the frequency and distribution characteristics of EH in VM for diagnostic use. Methods In a prospective case-control study of 200 participants, 75 patients with VM (49 females; mean age 46 years) and 75 with MD (36 females; mean age 55 years), according to the Bárány and International Headache Society, and 50 age-matched participants with normal vestibulocochlear testing (HP), were enrolled. Analyses of i MRI of the endolymphatic space included volumetric quantification, stepwise regression, correlation with neurotological parameters and support vector machine classification. Results EH was maximal in MD (80%), less in VM (32%) and minimal in HP (22%). EH was milder in VM (mean grade 0.3) compared with MD (mean grade 1.3). The intralabyrinthine distribution was preferably found in the vestibulum in VM, but mainly in the cochlea in MD. There was no interaural lateralisation of EH in VM but in the affected ear in MD. The grade of EH in the vestibulum was correlated in both conditions with the frequency and duration of the attacks. Conclusion Three features of the i MRI evaluation were most supportive for the diagnosis of VM at group and individual levels: (1) the bilateral manifestation, (2) the low-grade EH and (3) the intraaural distribution. All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249592","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}
引用次数: 0
Investigating colour vision and its structural correlates 15 years following a first demyelinating event 研究首次脱髓鞘事件 15 年后的色觉及其结构相关性
IF 11 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-12 DOI: 10.1136/jnnp-2024-334551
Charmaine Yam, Wallace J Brownlee, Ferran Prados Carrasco, Ahmed Toosy, Olga Ciccarelli
Background We investigated the long-term colour and contrast vision outcomes, 15 years after a first demyelinating event, with their structural correlates using optical coherence tomography (OCT) and brain MRI. Methods Patients recruited with their first demyelinating event, were invited~15 years later to undergo clinical assessments, OCT and brain MRI and were clinically classified according to multiple sclerosis (MS) phenotypes. Linear mixed models evaluated associations between visual outcomes, MS phenotypes and OCT measures. Results 94 patients were evaluated after a median of 14.3 years. 111 eyes affected by optic neuritis and 77 unaffected eyes were studied. Optic neuritis eyes displayed worse colour vision than unaffected eyes. Unaffected eyes showed worse colour vision in relapsing-remitting MS and secondary progressive MS (SPMS) than clinically isolated syndrome, while no similar discriminatory ability was seen for OCT measures. However, ganglion cell inner plexiform layer (GCIPL) was superior to peripapillary retinal nerve fibre layer (pRNFL) in predicting all visual outcomes. Worse colour vision was associated with lower retinal thicknesses and higher brain T2 lesion load; adding MRI volumetrics to macular GCIPL predictors did not improve model prediction of visual outcomes. Conclusions Colour vision was impaired in unaffected eyes, especially in SPMS. GCIPL thinning underpinned this impairment more than pRNFL, suggesting neuroaxonal loss as the pathobiological substrate. The correlation between worse colour vision and increasing T2 lesion load suggests that colour dysfunction reflects overall greater disease burden. Quantitative evaluation of colour vision in addition to OCT may be useful to assess disease severity in patients after a first demyelinating event. Data are available upon reasonable request. The data that support the findings of this study are available on request to suitably qualified investigators from the corresponding author.
背景 我们利用光学相干断层扫描(OCT)和脑核磁共振成像(MRI)研究了首次脱髓鞘事件发生 15 年后的长期颜色和对比度视力结果及其结构相关性。方法 招募首次发生脱髓鞘事件的患者,邀请他们在 15 年后接受临床评估、光学相干断层扫描(OCT)和脑磁共振成像,并根据多发性硬化(MS)表型进行临床分类。线性混合模型评估了视觉结果、多发性硬化表型和 OCT 测量之间的关联。结果 94 名患者在中位 14.3 年后接受了评估。研究了 111 只受视神经炎影响的眼睛和 77 只未受影响的眼睛。与未受影响的眼睛相比,视神经炎患者的色觉更差。与临床孤立综合征相比,复发性多发性硬化症和继发性进行性多发性硬化症(SPMS)未受影响的眼睛显示出更差的色觉,而 OCT 测量没有类似的判别能力。然而,在预测所有视觉结果方面,神经节细胞丛状内层(GCIPL)优于毛周视网膜神经纤维层(pRNFL)。较差的色觉与较低的视网膜厚度和较高的脑T2病变负荷有关;在黄斑GCIPL预测指标中加入核磁共振成像体积测量并不能改善模型对视觉结果的预测。结论 未受影响的眼睛,尤其是 SPMS 患者的色觉受损。与pRNFL相比,GCIPL变薄对色觉障碍的影响更大,这表明神经轴突缺失是其病理生物学基础。色觉减退与T2病变负荷增加之间的相关性表明,色觉功能障碍反映了总体上更大的疾病负担。除 OCT 外,色觉的定量评估可能有助于评估首次发生脱髓鞘事件后患者的疾病严重程度。如有合理要求,可提供相关数据。支持本研究结果的数据可应相应作者的要求提供给有资格的研究人员。
{"title":"Investigating colour vision and its structural correlates 15 years following a first demyelinating event","authors":"Charmaine Yam, Wallace J Brownlee, Ferran Prados Carrasco, Ahmed Toosy, Olga Ciccarelli","doi":"10.1136/jnnp-2024-334551","DOIUrl":"https://doi.org/10.1136/jnnp-2024-334551","url":null,"abstract":"Background We investigated the long-term colour and contrast vision outcomes, 15 years after a first demyelinating event, with their structural correlates using optical coherence tomography (OCT) and brain MRI. Methods Patients recruited with their first demyelinating event, were invited~15 years later to undergo clinical assessments, OCT and brain MRI and were clinically classified according to multiple sclerosis (MS) phenotypes. Linear mixed models evaluated associations between visual outcomes, MS phenotypes and OCT measures. Results 94 patients were evaluated after a median of 14.3 years. 111 eyes affected by optic neuritis and 77 unaffected eyes were studied. Optic neuritis eyes displayed worse colour vision than unaffected eyes. Unaffected eyes showed worse colour vision in relapsing-remitting MS and secondary progressive MS (SPMS) than clinically isolated syndrome, while no similar discriminatory ability was seen for OCT measures. However, ganglion cell inner plexiform layer (GCIPL) was superior to peripapillary retinal nerve fibre layer (pRNFL) in predicting all visual outcomes. Worse colour vision was associated with lower retinal thicknesses and higher brain T2 lesion load; adding MRI volumetrics to macular GCIPL predictors did not improve model prediction of visual outcomes. Conclusions Colour vision was impaired in unaffected eyes, especially in SPMS. GCIPL thinning underpinned this impairment more than pRNFL, suggesting neuroaxonal loss as the pathobiological substrate. The correlation between worse colour vision and increasing T2 lesion load suggests that colour dysfunction reflects overall greater disease burden. Quantitative evaluation of colour vision in addition to OCT may be useful to assess disease severity in patients after a first demyelinating event. Data are available upon reasonable request. The data that support the findings of this study are available on request to suitably qualified investigators from the corresponding author.","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186567","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}
引用次数: 0
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Journal of Neurology, Neurosurgery, and Psychiatry
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