Pub Date : 2024-12-01DOI: 10.1016/j.neurol.2024.09.004
S. Prange , S. Thobois
Impulse control disorders (ICD) are frequent and cumbersome behavioral disorders in patients with Parkinson's disease (PD). Understanding their pathophysiological underpinnings is crucial. Molecular imaging using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) clearly indicates preexisting vulnerability and abnormal sensitization of the pre- and postsynaptic dopaminergic system. Functional magnetic resonance imaging (fMRI) studies reveal abnormal connectivity within the reward system involving the ventral striatum and orbitofrontal cortex. These alterations pinpoint the dysfunction of reinforcement learning in ICD, which is biased toward the overvaluation of reward and underestimation of risk, and the deficit in inhibitory control mechanisms related to abnormal connectivity within and between the limbic and the associative and motor networks.
{"title":"Imaging of impulse control disorders in Parkinson's disease","authors":"S. Prange , S. Thobois","doi":"10.1016/j.neurol.2024.09.004","DOIUrl":"10.1016/j.neurol.2024.09.004","url":null,"abstract":"<div><div>Impulse control disorders (ICD) are frequent and cumbersome behavioral disorders in patients with Parkinson's disease (PD). Understanding their pathophysiological underpinnings is crucial. Molecular imaging using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) clearly indicates preexisting vulnerability and abnormal sensitization of the pre- and postsynaptic dopaminergic system. Functional magnetic resonance imaging (fMRI) studies reveal abnormal connectivity within the reward system involving the ventral striatum and orbitofrontal cortex. These alterations pinpoint the dysfunction of reinforcement learning in ICD, which is biased toward the overvaluation of reward and underestimation of risk, and the deficit in inhibitory control mechanisms related to abnormal connectivity within and between the limbic and the associative and motor networks.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 10","pages":"Pages 1078-1086"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.neurol.2024.08.008
J. Reis , D. Béquet , P.-M. Preux , E. Baldauf , M. Dumas
{"title":"Homage to professor Maurice Collard","authors":"J. Reis , D. Béquet , P.-M. Preux , E. Baldauf , M. Dumas","doi":"10.1016/j.neurol.2024.08.008","DOIUrl":"10.1016/j.neurol.2024.08.008","url":null,"abstract":"","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 10","pages":"Pages 998-999"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.neurol.2024.09.001
A. San-Galli , H. Chaumont , Q. Bourgeois , J. Roge , Q. Lobjois , P. Cabre
{"title":"Eculizumab as rescue therapy in a context of dramatic NMOSD attack: Report of two cases","authors":"A. San-Galli , H. Chaumont , Q. Bourgeois , J. Roge , Q. Lobjois , P. Cabre","doi":"10.1016/j.neurol.2024.09.001","DOIUrl":"10.1016/j.neurol.2024.09.001","url":null,"abstract":"","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 10","pages":"Pages 995-997"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.neurol.2023.12.013
S.A. Freeman , H. Zéphir
Anti-CD20 monoclonal antibodies are highly-effective B-cell-depleting therapies in multiple sclerosis (MS). These treatments have expanded the arsenal of highly effective disease-modifying therapies, and have changed the landscape in understanding the pathophysiology of MS and the natural course of the disease. Nevertheless, these treatments come at the cost of immunosuppression and risk of serious infections, diminished vaccination response and treatment-related secondary hypogammaglobulinemia. However, the COVID pandemic has given way to a possibility of readapting these therapies, with most notably extended dosing intervals. While these new strategies show efficacy in maintaining inflammatory MS disease control, and although it is tempting to speculate that tailoring CD20 therapies will reduce the negative outcomes of long-term immunosuppression, it is unknown whether they provide meaningful benefit in reducing the risk of treatment-related secondary hypogammaglobulinemia and serious infections. This review highlights the available anti-CD20 therapies that are available for treating MS patients, and sheds light on encouraging data, which propose that tailoring anti-CD20 monoclonal antibodies is the next step in rethinking the current treatment strategy.
{"title":"Anti-CD20 monoclonal antibodies in multiple sclerosis: Rethinking the current treatment strategy","authors":"S.A. Freeman , H. Zéphir","doi":"10.1016/j.neurol.2023.12.013","DOIUrl":"10.1016/j.neurol.2023.12.013","url":null,"abstract":"<div><div><span><span>Anti-CD20 monoclonal antibodies are highly-effective B-cell-depleting therapies in multiple sclerosis<span> (MS). These treatments have expanded the arsenal of highly effective disease-modifying therapies, and have changed the landscape in understanding the pathophysiology<span> of MS and the natural course of the disease. Nevertheless, these treatments come at the cost of immunosuppression and risk of serious infections, diminished </span></span></span>vaccination<span> response and treatment-related secondary hypogammaglobulinemia<span>. However, the COVID pandemic has given way to a possibility of readapting these therapies, with most notably extended dosing intervals. While these new strategies show efficacy in maintaining inflammatory MS disease control, and although it is tempting to speculate that tailoring </span></span></span>CD20<span><span> therapies will reduce the negative outcomes of long-term immunosuppression, it is unknown whether they provide meaningful benefit in reducing the risk of treatment-related secondary </span>hypogammaglobulinemia and serious infections. This review highlights the available anti-CD20 therapies that are available for treating MS patients, and sheds light on encouraging data, which propose that tailoring anti-CD20 monoclonal antibodies is the next step in rethinking the current treatment strategy.</span></div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 10","pages":"Pages 1047-1058"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140774867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.neurol.2023.07.017
H. Abbasi , F. Shakouri , R. Mosaddeghi-Heris , E. Gholipour-Khalili , F. Jahanshahlou , S. Sanaie , A. Naseri , M. Talebi
Background
Mediterranean-like diet is an anti-inflammatory diet with high-fiber consumption and lower intake of saturated fatty acids which is proposed to have beneficial effects in patients with multiple sclerosis (MS). This investigation aims to explore the impacts of this style of diet on people living with MS, based on clinical evidence.
Methods
This study was conducted following the 2020 version of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Both interventional and observational clinical studies which evaluated the effects of Mediterranean-like diets on MS patients were considered for inclusion. Review articles, letters, commentaries, case reports, non-English papers, and conference abstracts were excluded. PubMed, Web of Science, Scopus, and EMBASE databases were searched until March 23rd, 2023, and risk of bias in randomized-controlled trials (RCTs) was evaluated based on the second version of the Cochrane RoB assessment tool (RoB.2). In addition, for the observational studies, Joanna Briggs Institute (JBI)’s critical appraisal tools were utilized.
Results
Of 161 records that were screened in the title/abstract stage, 13 reports of 11 studies were included in the systematic review. Three RCTs (including one pilot RCT), and eight observational studies reported the effects of Mediterranean-like diets on people living with MS. The sample sizes in clinical trials varied between 36 and 147 and for observational studies between 30 and 563 patients. Evidence suggested positive effects of a Mediterranean-like diet on inflammatory status and MS-related symptoms such as fatigue, quality of life, attack rate, and cognitive dysfunction.
Discussion
This systematic review pointed out possible beneficial effects of Mediterranean-like diets for MS patients. The limited number of well-designed RCTs was the main limitation of this study; therefore, large-scale multiple-center interventional studies are suggested. Variety in the assessed outcomes, study designs, and groups of the studies prevented meta-analysis which was the other limitation of this study.
地中海式饮食是一种高纤维摄入和低饱和脂肪酸摄入的抗炎饮食，被认为对多发性硬化症（MS）患者有有益作用。本研究旨在根据临床证据，探讨这种饮食方式对多发性硬化症患者的影响。方法本研究遵循2020年版本的系统评价和荟萃分析首选报告项目（PRISMA）声明进行。评估地中海式饮食对多发性硬化症患者影响的干预性和观察性临床研究均被纳入考虑。综述文章、信函、评论、病例报告、非英文论文和会议摘要被排除在外。检索PubMed、Web of Science、Scopus和EMBASE数据库至2023年3月23日，基于Cochrane第二版RoB评估工具（rob2）评估随机对照试验（RCTs）的偏倚风险。此外，在观察性研究中，使用了乔安娜布里格斯研究所（JBI）的批判性评估工具。结果在标题/摘要阶段筛选的161篇文献中，11篇研究的13篇报道被纳入系统评价。3项随机对照试验（包括1项试点随机对照试验）和8项观察性研究报告了地中海式饮食对ms患者的影响。临床试验的样本量在36 ~ 147例之间，观察性研究的样本量在30 ~ 563例之间。有证据表明，地中海式饮食对炎症状态和ms相关症状（如疲劳、生活质量、发病率和认知功能障碍）有积极影响。本系统综述指出地中海式饮食对多发性硬化症患者可能的有益作用。设计良好的随机对照试验数量有限是本研究的主要局限性；因此，建议开展大规模的多中心介入研究。评估结果、研究设计和研究分组的多样性阻碍了meta分析，这是本研究的另一个局限性。
{"title":"Mediterranean-like diets in multiple sclerosis: A systematic review","authors":"H. Abbasi , F. Shakouri , R. Mosaddeghi-Heris , E. Gholipour-Khalili , F. Jahanshahlou , S. Sanaie , A. Naseri , M. Talebi","doi":"10.1016/j.neurol.2023.07.017","DOIUrl":"10.1016/j.neurol.2023.07.017","url":null,"abstract":"<div><h3>Background</h3><div>Mediterranean-like diet is an anti-inflammatory diet with high-fiber consumption and lower intake of saturated fatty acids<span> which is proposed to have beneficial effects in patients with multiple sclerosis (MS). This investigation aims to explore the impacts of this style of diet on people living with MS, based on clinical evidence.</span></div></div><div><h3>Methods</h3><div>This study was conducted following the 2020 version of the Preferred Reporting Items for Systematic Reviews<span><span> and Meta-analyses (PRISMA) statement. Both interventional and observational clinical studies which evaluated the effects of Mediterranean-like diets on MS patients were considered for inclusion. Review articles, letters, commentaries, case reports, non-English papers, and conference abstracts were excluded. PubMed, Web of Science, </span>Scopus<span>, and EMBASE databases were searched until March 23rd, 2023, and risk of bias in randomized-controlled trials (RCTs) was evaluated based on the second version of the Cochrane RoB assessment tool (RoB.2). In addition, for the observational studies, Joanna Briggs Institute (JBI)’s critical appraisal tools were utilized.</span></span></div></div><div><h3>Results</h3><div><span>Of 161 records that were screened in the title/abstract stage, 13 reports of 11 studies were included in the systematic review. Three RCTs (including one pilot RCT), and eight observational studies reported the effects of Mediterranean-like diets on people living with MS. The sample sizes in </span>clinical trials<span><span> varied between 36 and 147 and for observational studies between 30 and 563 patients. Evidence suggested positive effects of a Mediterranean-like diet on inflammatory status and MS-related symptoms such as fatigue, quality of life, attack rate, and </span>cognitive dysfunction.</span></div></div><div><h3>Discussion</h3><div>This systematic review pointed out possible beneficial effects of Mediterranean-like diets for MS patients. The limited number of well-designed RCTs was the main limitation of this study; therefore, large-scale multiple-center interventional studies are suggested. Variety in the assessed outcomes, study designs, and groups of the studies prevented meta-analysis which was the other limitation of this study.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 10","pages":"Pages 1021-1030"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136128435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.neurol.2023.10.015
E. Drouin , L. Tatu , P. Hautecoeur
Jean Lhermitte (1877–1959), the French neurologist and psychiatrist, is most often associated with the sign he described in three patients with multiple sclerosis, back in 1927. In 1937, Lhermitte analytically studied a series of 28 amputees experiencing phantom limb sensations further to amputations dating between 1891 and 1934. After having described the main clinical characteristics of this unpublished series, we will detail the ideas advanced by Jean Lhermitte regarding the phenomenon of the phantom limb. Lhermitte will use these observations to develop conceptions of consciousness and the body schema encompassing very modern resonances.
Jean Lhermitte(1877-1959)，法国神经学家和精神病学家，最常与他在1927年描述的三名多发性硬化症患者的症状联系在一起。1937年，Lhermitte分析研究了一系列28名截肢者，他们经历了1891年至1934年间截肢后的幻肢感觉。在描述了这个未发表的系列的主要临床特征之后，我们将详细介绍Jean Lhermitte关于幻肢现象的观点。Lhermitte将利用这些观察来发展意识的概念以及包含现代共鸣的身体图式。
{"title":"What you feel is not always what you’ve got. Jean Lhermitte (1877–1959) and the phantom limb phenomenon","authors":"E. Drouin , L. Tatu , P. Hautecoeur","doi":"10.1016/j.neurol.2023.10.015","DOIUrl":"10.1016/j.neurol.2023.10.015","url":null,"abstract":"<div><div>Jean Lhermitte (1877–1959), the French neurologist and psychiatrist, is most often associated with the sign he described in three patients with multiple sclerosis<span><span>, back in 1927. In 1937, Lhermitte analytically studied a series of 28 amputees experiencing </span>phantom limb sensations further to amputations dating between 1891 and 1934. After having described the main clinical characteristics of this unpublished series, we will detail the ideas advanced by Jean Lhermitte regarding the phenomenon of the phantom limb. Lhermitte will use these observations to develop conceptions of consciousness and the body schema encompassing very modern resonances.</span></div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 10","pages":"Pages 1145-1150"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139014669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-14DOI: 10.1016/j.neurol.2024.10.005
M Khamaysa, M El Mendili, V Marchand, G Querin, P-F Pradat
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons in the cortex, brainstem, and spinal cord. This degeneration leads to muscular weakness, progressively impairing motor functions and ultimately resulting in respiratory failure. The clinical, genetic, and pathological heterogeneity of ALS, combined with the absence of reliable biomarkers, significantly challenge the efficacy of therapeutic trials. Despite these hurdles, neuroimaging, and particularly spinal cord imaging, has emerged as a promising tool. It provides insights into the involvement of both upper and lower motor neurons. Quantitative spinal imaging has the potential to facilitate early diagnosis, enable accurate monitoring of disease progression, and refine the design of clinical trials. In this review, we explore the utility of spinal cord imaging within the broader context of developing spinal imaging biomarkers in ALS. We focus on a both diagnostic and prognostic biomarker in ALS, highlighting its pivotal role in elucidating the disease's underlying pathology. We also discuss the existing limitations and future avenues for research, aiming to bridge the translational gap between academic research and its application in clinical practice and therapeutic trials.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是大脑皮层、脑干和脊髓中的运动神经元逐渐退化。这种退化导致肌肉无力，逐渐损害运动功能，最终导致呼吸衰竭。渐冻人症在临床、遗传和病理上的异质性，再加上缺乏可靠的生物标志物，给治疗试验的疗效带来了巨大挑战。尽管存在这些障碍，神经成像，尤其是脊髓成像，已成为一种很有前途的工具。它可以深入了解上下运动神经元的参与情况。脊髓定量成像具有促进早期诊断、准确监测疾病进展和完善临床试验设计的潜力。在本综述中，我们将在开发 ALS 脊柱成像生物标记物的大背景下探讨脊髓成像的效用。我们将重点放在 ALS 的诊断和预后生物标志物上，强调其在阐明该疾病潜在病理方面的关键作用。我们还讨论了现有的局限性和未来的研究途径，旨在弥合学术研究与临床实践和治疗试验应用之间的转化差距。
{"title":"Quantitative spinal cord imaging: Early ALS diagnosis and monitoring of disease progression.","authors":"M Khamaysa, M El Mendili, V Marchand, G Querin, P-F Pradat","doi":"10.1016/j.neurol.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.neurol.2024.10.005","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons in the cortex, brainstem, and spinal cord. This degeneration leads to muscular weakness, progressively impairing motor functions and ultimately resulting in respiratory failure. The clinical, genetic, and pathological heterogeneity of ALS, combined with the absence of reliable biomarkers, significantly challenge the efficacy of therapeutic trials. Despite these hurdles, neuroimaging, and particularly spinal cord imaging, has emerged as a promising tool. It provides insights into the involvement of both upper and lower motor neurons. Quantitative spinal imaging has the potential to facilitate early diagnosis, enable accurate monitoring of disease progression, and refine the design of clinical trials. In this review, we explore the utility of spinal cord imaging within the broader context of developing spinal imaging biomarkers in ALS. We focus on a both diagnostic and prognostic biomarker in ALS, highlighting its pivotal role in elucidating the disease's underlying pathology. We also discuss the existing limitations and future avenues for research, aiming to bridge the translational gap between academic research and its application in clinical practice and therapeutic trials.</p>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.neurol.2024.07.002
J. Cleaver , B. Ceronie , C. Strippel , A. Handel , S.R. Irani
The past two decades have seen a considerable paradigm shift in the way autoimmune CNS disorders are considered, diagnosed, and treated; largely due to the discovery of novel autoantibodies directed at neuroglial surface or intracellular targets. This approach has enabled multiple bona fide CNS autoantibody-associated diseases to thoroughly infiltrate the sphere of clinical neurology, facilitating advances in patient outcomes. This review focusses on the fundamental immunological concepts behind CNS autoantibody-associated diseases. First, we briefly review the broad phenotypic profiles of these conditions. Next, we explore concepts around immune checkpoints and the related B cell lineage. Thirdly, the sources of autoantibody production are discussed alongside triggers of tolerance failure, including neoplasms, infections and iatrogenic therapies. Penultimately, the role of T cells and leucocyte trafficking into the CNS are reviewed. Finally, biological insights from responses to targeted immunotherapies in different CNS autoantibody-associated diseases are summarised. The continued and rapid expansion of the CNS autoantibody-associated field holds promise for further improved diagnostic and therapeutic paradigms, ultimately leading to further improvements in patient outcomes.
在过去二十年中，自身免疫性中枢神经系统疾病的考虑、诊断和治疗方式发生了巨大的范式转变，这主要归功于针对神经胶质细胞表面或细胞内靶点的新型自身抗体的发现。这种方法使多种真正的中枢神经系统自身抗体相关疾病彻底渗入临床神经病学领域，促进了患者治疗效果的改善。本综述重点探讨中枢神经系统自身抗体相关疾病背后的基本免疫学概念。首先，我们简要回顾了这些疾病的广泛表型特征。其次，我们探讨了免疫检查点和相关 B 细胞系的概念。第三，讨论自身抗体产生的来源以及耐受失败的诱因，包括肿瘤、感染和先天性疗法。最后，回顾了 T 细胞的作用和白细胞向中枢神经系统的迁移。最后，总结了不同中枢神经系统自身抗体相关疾病对靶向免疫疗法反应的生物学启示。中枢神经系统自身抗体相关领域的持续快速发展为进一步改进诊断和治疗范例带来了希望，最终将进一步改善患者的预后。
{"title":"The immunology underlying CNS autoantibody diseases","authors":"J. Cleaver , B. Ceronie , C. Strippel , A. Handel , S.R. Irani","doi":"10.1016/j.neurol.2024.07.002","DOIUrl":"10.1016/j.neurol.2024.07.002","url":null,"abstract":"<div><div>The past two decades have seen a considerable paradigm shift in the way autoimmune CNS disorders are considered, diagnosed, and treated; largely due to the discovery of novel autoantibodies directed at neuroglial surface or intracellular targets. This approach has enabled multiple <em>bona fide</em> CNS autoantibody-associated diseases to thoroughly infiltrate the sphere of clinical neurology, facilitating advances in patient outcomes. This review focusses on the fundamental immunological concepts behind CNS autoantibody-associated diseases. First, we briefly review the broad phenotypic profiles of these conditions. Next, we explore concepts around immune checkpoints and the related B cell lineage. Thirdly, the sources of autoantibody production are discussed alongside triggers of tolerance failure, including neoplasms, infections and iatrogenic therapies. Penultimately, the role of T cells and leucocyte trafficking into the CNS are reviewed. Finally, biological insights from responses to targeted immunotherapies in different CNS autoantibody-associated diseases are summarised. The continued and rapid expansion of the CNS autoantibody-associated field holds promise for further improved diagnostic and therapeutic paradigms, ultimately leading to further improvements in patient outcomes.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 916-930"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.neurol.2024.08.003
M. Guasp , J. Dalmau
The concept that many neurologic and psychiatric disorders of unknown cause are immune-mediated has evolved fast during the past 20 years. The main contribution to the expansion of this field has been the discovery of antibodies that attack neuronal or glial cell-surface proteins or receptors, directly modifying their structure and function. These antibodies facilitate the diagnosis and prompt treatment of patients who often improve with immunotherapy. The identification of this group of diseases, collectively named “autoimmune encephalitides”, was preceded by many years of investigations on other autoimmune CNS disorders in which the antibodies are against intracellular proteins, occur more frequently with cancer, and associate with cytotoxic T-cell responses that are less responsive to immunotherapy. Here, we first trace the recent history of the autoimmune encephalitides and address how to assess the clinical value and implement in our practice the rapid pace of autoantibody discovery. In addition, we review recent developments in the post-acute stage of the two main autoimmune encephalitides (NMDAR and LGI1) focusing on symptoms that are frequently overlooked or missed, and therefore undertreated. Because a better understanding of the pathophysiology of these diseases relies on animal models, we examine currently available studies, recognizing the existing needs for better and all-inclusive neuro-immunobiological models. Finally, we assess the status of biomarkers of disease outcome, clinical scales, current treatment strategies, and emerging therapies including CAR T-cell technology. Altogether, this overview is intended to identify gaps of knowledge and provide suggestions for improvement and insights for future research.
在过去的 20 年中，许多原因不明的神经和精神疾病都是由免疫介导的这一概念得到了快速发展。这一领域的发展主要得益于抗体的发现，这些抗体可以攻击神经元或神经胶质细胞表面蛋白或受体，直接改变它们的结构和功能。这些抗体为诊断和及时治疗患者提供了便利，这些患者往往在接受免疫疗法后病情有所好转。在发现这一类疾病（统称为 "自身免疫性脑炎"）之前，我们已对其他自身免疫性中枢神经系统疾病进行了多年研究，这些疾病的抗体针对细胞内蛋白，更常与癌症同时发生，并与对免疫疗法反应较弱的细胞毒性T细胞反应相关联。在此，我们首先回顾了自身免疫性脑病的近代史，并探讨了如何评估自身抗体的临床价值，以及如何在实践中快速应用自身抗体的发现。此外，我们还回顾了两种主要自身免疫性脑炎（NMDAR 和 LGI1）急性期后阶段的最新进展，重点关注那些经常被忽视或遗漏、因而治疗不足的症状。由于更好地了解这些疾病的病理生理学有赖于动物模型，我们审视了现有的研究，认识到目前需要更好的、包罗万象的神经免疫生物学模型。最后，我们评估了疾病结局生物标志物、临床量表、当前治疗策略以及包括 CAR T 细胞技术在内的新兴疗法的现状。总之，本综述旨在找出知识差距，为未来研究提供改进建议和见解。
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Pub Date : 2024-11-01DOI: 10.1016/j.neurol.2024.08.007
A. Farina , M. Villagrán-García , B. Joubert
Immune checkpoint inhibitors lead to effective antitumour responses but also to immune-related adverse events (irAEs), which affect the nervous system in 1–5% of patients. Encephalitis is the most frequent central nervous system irAE and is clinically relevant due to its high severity and mortality. Early diagnosis is crucial but is hampered by the broad list of alternative diagnoses, the lack of established diagnostic criteria, and the need of extensive diagnostic procedures (e.g., spinal tap, brain MRI) alongside expert neurological evaluation. Additionally, the response to corticosteroids is inconsistent, and the management of corticosteroid-refractory patients remains poorly defined. This mini-review discusses the role of various soluble biomarkers in the diagnosis, prognostication, and management of ICI-encephalitis. Neural antibodies, which are well-established biomarkers of autoimmune and paraneoplastic encephalitis, are found in only a subset of ICI-encephalitis, in which they can aid to establish the diagnosis. The most prevalent are paraneoplastic neurological syndromes (PNS)-associated antibodies, which are found almost exclusively in focal ICI-encephalitis syndromes and are associated with poor outcomes, possibly due to predominantly cytotoxic T cell involvement leading to irreversible neuronal loss. Beside antibodies, serum brain injury biomarkers such as NfL and S100B are elevated in ICI-encephalitis and, even if non-specific, may be useful as a routine test to quickly identify patients in whom neurological evaluation and second-level diagnostic procedures should be prioritized. Additionally, higher serum and CSF NfL levels have been associated with lack of treatment response in ICI-encephalitis, suggesting they may have a prognostic role. Among cytokines, elevated interleukin 6 (IL6) levels have been observed in serum and/or CSF samples of some patients with ICI-encephalitis, but the role of IL6 as a biomarker for response to IL6-directed therapies requires further investigation. Likewise, the value of other biomarkers, including T cells markers and HLA haplotypes, still needs to be evaluated in large cohorts. Overall, neural antibodies are important diagnostic and prognostic biomarkers in ICI-encephalitis, and other soluble biomarkers, especially NfL, deserve further investigation since they have a promising application in clinical practice.
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