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 : 2024-11-06DOI: 10.1016/j.neurol.2024.10.003
S Braca, R De Simone, A Stornaiuolo, G Cretella, A Miele, C V Russo
Background: Medication overuse headache (MOH) is a condition where pain relief medications cause chronic headaches due to excessive use. Recent advancements highlight the effectiveness of preventive treatments like anti-CGRP monoclonal antibodies. Current strategies combine medication withdrawal and preventive treatments, with corticosteroids traditionally used to ease withdrawal symptoms.
Methods: This is a prospective three-arm observational cohort study comparing the effectiveness and safety of galcanezumab alone, galcanezumab plus prednisone and prednisone alone for the treatment of MOH. We enrolled 75 patients. Prednisone was administered at an initial dose of 50mg daily, and then tapered off over 28days. Duration of follow-up was 3months.
Results: All treatments proved effective (P<0.001). We found a significant reduction of mean monthly days with headache in the galcanezumab plus prednisone group (baseline: 25, IQR: 20-30; after 3months: 7, IQR: 5-10), in the galcanezumab group (baseline: 25, IQR: 20-30; after 3months: 10, IQR: 5-14) and in the Prednisone group (baseline: 25, IQR: 20-28; after 3months: median: 15 days, IQR: 8-22days). Patients treated with prednisone reported a higher incidence of side effects (P=0.002).
Conclusion: Our study indicates that both galcanezumab and prednisone decrease the frequency of headaches in patients with MOH. The combined usage of these treatments showed the highest reduction in mean monthly headache days. However, treatment with prednisone determined a significant rate of adverse events, therefore we suggest its use only in unresponsive patients. In all other patients galcanezumab appears to be a safe and effective option.
{"title":"Adding corticosteroids to galcanezumab in medication overuse headache: A three-arm head-to-head prospective observational cohort study.","authors":"S Braca, R De Simone, A Stornaiuolo, G Cretella, A Miele, C V Russo","doi":"10.1016/j.neurol.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.neurol.2024.10.003","url":null,"abstract":"<p><strong>Background: </strong>Medication overuse headache (MOH) is a condition where pain relief medications cause chronic headaches due to excessive use. Recent advancements highlight the effectiveness of preventive treatments like anti-CGRP monoclonal antibodies. Current strategies combine medication withdrawal and preventive treatments, with corticosteroids traditionally used to ease withdrawal symptoms.</p><p><strong>Methods: </strong>This is a prospective three-arm observational cohort study comparing the effectiveness and safety of galcanezumab alone, galcanezumab plus prednisone and prednisone alone for the treatment of MOH. We enrolled 75 patients. Prednisone was administered at an initial dose of 50mg daily, and then tapered off over 28days. Duration of follow-up was 3months.</p><p><strong>Results: </strong>All treatments proved effective (P<0.001). We found a significant reduction of mean monthly days with headache in the galcanezumab plus prednisone group (baseline: 25, IQR: 20-30; after 3months: 7, IQR: 5-10), in the galcanezumab group (baseline: 25, IQR: 20-30; after 3months: 10, IQR: 5-14) and in the Prednisone group (baseline: 25, IQR: 20-28; after 3months: median: 15 days, IQR: 8-22days). Patients treated with prednisone reported a higher incidence of side effects (P=0.002).</p><p><strong>Conclusion: </strong>Our study indicates that both galcanezumab and prednisone decrease the frequency of headaches in patients with MOH. The combined usage of these treatments showed the highest reduction in mean monthly headache days. However, treatment with prednisone determined a significant rate of adverse events, therefore we suggest its use only in unresponsive patients. In all other patients galcanezumab appears to be a safe and effective option.</p>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605926","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 : 2024-11-06DOI: 10.1016/j.neurol.2024.10.001
Nicolas Gaillard, Jean-Claude Deharo, Laurent Suissa, Pascal Defaye, Igor Sibon, Christophe Leclercq, Sonia Alamowitch, Céline Guidoux, Ariel Cohen
Atrial fibrillation (AF) is the primary cause of ischaemic stroke and transient ischaemic attack (TIA). AF is associated with a high risk of recurrence, which can be reduced using optimal prevention strategies, mainly anticoagulant therapy. The availability of effective prophylaxis justifies the need for a significant, coordinated and thorough transdisciplinary effort to screen for AF associated with stroke. A recent French national survey, initiated and supported by the Société française neurovasculaire (SFNV) and the Société française de cardiologie (SFC), revealed many shortcomings, such as the absence or inadequacy of telemetry equipment in more than half of stroke units, insufficient and highly variable access to monitoring tools, delays in performing screening tests, heterogeneous access to advanced or connected ambulatory monitoring techniques, and a lack of dedicated human resources. The present scientific document has been prepared on the initiative of the SFNV and the SFC with the aim of helping to address the current shortcomings and gaps, to promote efficient and cost-effective AF detection, and to improve and, where possible, homogenize the quality of practice in AF screening among stroke units and outpatient post-stroke care networks. The working group, composed of cardiologists and vascular neurologists who are experts in the field and are nominated by their peers, reviewed the literature to propose statements, which were discussed in successive cycles, and maintained, either by consensus or by vote, as appropriate. The text was then submitted to the SFNV and SFC board members for review. This scientific statement document argues for the widespread development of patient pathways to enable the most efficient AF screening after stroke. This assessment should be carried out by a multidisciplinary team, including expert cardiologists and vascular neurologists.
心房颤动(房颤)是缺血性中风和短暂性脑缺血发作(TIA)的主要原因。心房颤动具有很高的复发风险,而采用最佳预防策略(主要是抗凝疗法)可以降低复发风险。有效的预防措施的可用性证明,有必要开展一项重要、协调和彻底的跨学科工作,筛查与中风相关的房颤。最近,由法国神经血管协会(SFNV)和法国心脏病协会(SFC)发起并支持的一项法国全国性调查显示了许多不足之处,如超过半数的中风科室没有遥测设备或遥测设备不足、监测工具不足且使用情况参差不齐、筛查测试延迟、先进或联网的非卧床监测技术使用情况参差不齐,以及缺乏专门的人力资源。本科学文件由国家卒中筛查中心(SFNV)和国家急性心肌梗死筛查中心(SFC)共同编写,旨在帮助解决目前存在的不足和差距,促进高效、经济的心房颤动检测,提高并尽可能统一卒中单元和卒中后门诊护理网络的心房颤动筛查实践质量。工作组由该领域的心脏病专家和血管神经科专家组成,他们由同行提名,通过查阅文献提出声明,并在连续的周期内对声明进行讨论,根据情况以协商一致或投票的方式维持声明。声明文本随后提交给 SFNV 和 SFC 董事会成员审阅。本科学声明文件主张广泛制定患者路径,以便在卒中后进行最有效的房颤筛查。该评估应由包括心脏病专家和血管神经学家在内的多学科团队进行。
{"title":"Reprint of: Scientific statement from the French neurovascular and cardiac societies for improved detection of atrial fibrillation after ischaemic stroke and transient ischaemic attack.","authors":"Nicolas Gaillard, Jean-Claude Deharo, Laurent Suissa, Pascal Defaye, Igor Sibon, Christophe Leclercq, Sonia Alamowitch, Céline Guidoux, Ariel Cohen","doi":"10.1016/j.neurol.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.neurol.2024.10.001","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is the primary cause of ischaemic stroke and transient ischaemic attack (TIA). AF is associated with a high risk of recurrence, which can be reduced using optimal prevention strategies, mainly anticoagulant therapy. The availability of effective prophylaxis justifies the need for a significant, coordinated and thorough transdisciplinary effort to screen for AF associated with stroke. A recent French national survey, initiated and supported by the Société française neurovasculaire (SFNV) and the Société française de cardiologie (SFC), revealed many shortcomings, such as the absence or inadequacy of telemetry equipment in more than half of stroke units, insufficient and highly variable access to monitoring tools, delays in performing screening tests, heterogeneous access to advanced or connected ambulatory monitoring techniques, and a lack of dedicated human resources. The present scientific document has been prepared on the initiative of the SFNV and the SFC with the aim of helping to address the current shortcomings and gaps, to promote efficient and cost-effective AF detection, and to improve and, where possible, homogenize the quality of practice in AF screening among stroke units and outpatient post-stroke care networks. The working group, composed of cardiologists and vascular neurologists who are experts in the field and are nominated by their peers, reviewed the literature to propose statements, which were discussed in successive cycles, and maintained, either by consensus or by vote, as appropriate. The text was then submitted to the SFNV and SFC board members for review. This scientific statement document argues for the widespread development of patient pathways to enable the most efficient AF screening after stroke. This assessment should be carried out by a multidisciplinary team, including expert cardiologists and vascular neurologists.</p>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605927","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。
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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.
{"title":"Soluble biomarkers for immune checkpoint inhibitor-related encephalitis: A mini-review","authors":"A. Farina , M. Villagrán-García , B. Joubert","doi":"10.1016/j.neurol.2024.08.007","DOIUrl":"10.1016/j.neurol.2024.08.007","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 982-988"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.neurol.2024.09.002
J.-C. Antoine
Over the past 30 years, about 20 antibodies have been identified in immune-mediated neuropathies, recognizing membrane or intracellular proteins or glycolipids of neuron and Schwann cells. This article reviews the different methods used for their detection, what we know about their pathogenic role, how they have helped identify several disorders, and how they are essential for diagnosis. Despite sustained efforts, some immune-mediated disorders still lack identified autoantibodies, notably the classical form of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. The reasons for this are discussed. The article also tries to determine potential future developments in antibody research, particularly the use of omic approaches and the search for other types of biomarkers beyond diagnostic ones, such as those that can identify patients who will respond to a given treatment.
{"title":"Antibodies in immune-mediated peripheral neuropathies. Where are we in 2024?","authors":"J.-C. Antoine","doi":"10.1016/j.neurol.2024.09.002","DOIUrl":"10.1016/j.neurol.2024.09.002","url":null,"abstract":"<div><div>Over the past 30 years, about 20 antibodies have been identified in immune-mediated neuropathies, recognizing membrane or intracellular proteins or glycolipids of neuron and Schwann cells. This article reviews the different methods used for their detection, what we know about their pathogenic role, how they have helped identify several disorders, and how they are essential for diagnosis. Despite sustained efforts, some immune-mediated disorders still lack identified autoantibodies, notably the classical form of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. The reasons for this are discussed. The article also tries to determine potential future developments in antibody research, particularly the use of omic approaches and the search for other types of biomarkers beyond diagnostic ones, such as those that can identify patients who will respond to a given treatment.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 876-887"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.neurol.2024.08.002
E. Peter , P. Dumez , J. Honnorat , V. Desestret
Paraneoplastic neurological syndromes (PNS) are rare autoimmune disorders triggered by the presence of a cancer. The autoimmunity is herein directed against proteins expressed both in the tumor and in the nervous system, namely the onconeural antigens, against which are directed specific autoantibodies, each of them characterizing a neurological syndrome. The mechanisms of the immune tolerance breakdown in PNS leading to the production of specific autoantibodies directed against the nervous system and leading to the immune attack begins to be explained. Each syndrome is associated with a specific histo-molecular subtype of tumor suggesting a link between the PNS genesis and oncogenesis. The expression of the onconeural antigen by these tumors is insufficient to explain the immune tolerance breakdown. In some PNS tumors, alterations of the antigen have been identified: mutations, gene copy number variation and overexpression of transcript and protein. But in others PNS, no such molecular alterations of the onconeural antigens have been demonstrated. In these cases, other mechanisms of neoantigen generation that may be involved remain to be deciphered. Cancer outcomes of PNS tumors are also characterized by the high frequency of lymph node metastasis at diagnosis. At the primary tumor site, the antitumor immune reaction seems to be particularly intense and characterized by a prominence of B-cell and Ig-secreting plasma cells that may generate the autoantibody secretion. The immune control mechanisms leading to such organization of the immune attack are not known to date. Renewed research efforts are thus needed to better understand the mechanism of immune tolerance breakdown in each PNS and determine potential targets to meet the therapeutic challenges posed by these rare disorders.
{"title":"Mechanisms of immune tolerance breakdown in paraneoplastic neurological syndromes","authors":"E. Peter , P. Dumez , J. Honnorat , V. Desestret","doi":"10.1016/j.neurol.2024.08.002","DOIUrl":"10.1016/j.neurol.2024.08.002","url":null,"abstract":"<div><div>Paraneoplastic neurological syndromes (PNS) are rare autoimmune disorders triggered by the presence of a cancer. The autoimmunity is herein directed against proteins expressed both in the tumor and in the nervous system, namely the onconeural antigens, against which are directed specific autoantibodies, each of them characterizing a neurological syndrome. The mechanisms of the immune tolerance breakdown in PNS leading to the production of specific autoantibodies directed against the nervous system and leading to the immune attack begins to be explained. Each syndrome is associated with a specific histo-molecular subtype of tumor suggesting a link between the PNS genesis and oncogenesis. The expression of the onconeural antigen by these tumors is insufficient to explain the immune tolerance breakdown. In some PNS tumors, alterations of the antigen have been identified: mutations, gene copy number variation and overexpression of transcript and protein. But in others PNS, no such molecular alterations of the onconeural antigens have been demonstrated. In these cases, other mechanisms of neoantigen generation that may be involved remain to be deciphered. Cancer outcomes of PNS tumors are also characterized by the high frequency of lymph node metastasis at diagnosis. At the primary tumor site, the antitumor immune reaction seems to be particularly intense and characterized by a prominence of B-cell and Ig-secreting plasma cells that may generate the autoantibody secretion. The immune control mechanisms leading to such organization of the immune attack are not known to date. Renewed research efforts are thus needed to better understand the mechanism of immune tolerance breakdown in each PNS and determine potential targets to meet the therapeutic challenges posed by these rare disorders.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 931-939"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.neurol.2024.08.004
R. Marignier
In this mini-review, we focus on novelties in the field of neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD). We first describe the proposed criteria for MOGAD and evaluate their impact and potential limitations, with a highlight on the subgroups of patients tested MOG-antibody positive only in the cerebrospinal fluid. We then propose a brief state of the art on the current knowledge on the so-call “double seronegative” NMOSD group, regarding nosology, clinical, biological and imaging features and the unmet need in this field. The last part is dedicating to the present and future of acute treatment in NMSOD and MOGAD.
{"title":"What's new in NMOSD and MOGAD?","authors":"R. Marignier","doi":"10.1016/j.neurol.2024.08.004","DOIUrl":"10.1016/j.neurol.2024.08.004","url":null,"abstract":"<div><div>In this mini-review, we focus on novelties in the field of neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD). We first describe the proposed criteria for MOGAD and evaluate their impact and potential limitations, with a highlight on the subgroups of patients tested MOG-antibody positive only in the cerebrospinal fluid. We then propose a brief state of the art on the current knowledge on the so-call “double seronegative” NMOSD group, regarding nosology, clinical, biological and imaging features and the unmet need in this field. The last part is dedicating to the present and future of acute treatment in NMSOD and MOGAD.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 957-962"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.neurol.2024.10.004
J. Honnorat
{"title":"History and novelties in autoimmune encephalitis and paraneoplastic neurological syndromes","authors":"J. Honnorat","doi":"10.1016/j.neurol.2024.10.004","DOIUrl":"10.1016/j.neurol.2024.10.004","url":null,"abstract":"","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 845-847"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554670","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}