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}
Pub Date : 2024-11-01DOI: 10.1016/j.neurol.2024.08.006
T.J. Hartung , F. Bartels , J. Kuchling , S. Krohn , J. Leidel , M. Mantwill , K. Wurdack , S. Yogeshwar , M. Scheel , C. Finke
Autoimmune encephalitis encompasses a spectrum of conditions characterized by distinct clinical features and magnetic resonance imaging (MRI) findings. Here, we review the literature on acute MRI changes in the most common autoimmune encephalitis variants. In N-methyl-D-aspartate (NMDA) receptor encephalitis, most patients have a normal MRI in the acute stage. When lesions are present in the acute stage, they are typically subtle and non-specific white matter lesions that do not correspond with the clinical syndrome. In some NMDA receptor encephalitis cases, these T2-hyperintense lesions may be indicative of an NMDA receptor encephalitis overlap syndrome with simultaneous co-existence of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Encephalitis with leucine-rich glioma-inactivated 1 (LGI1)-, contactin-associated protein-like 2 (CASPR2)- or glutamic acid decarboxylase (GAD)- antibodies typically presents as limbic encephalitis (LE) with unilateral or bilateral T2/fluid attenuated inversion recovery (FLAIR) hyperintensities in the medial temporal lobe that can progress to hippocampal atrophy. Gamma aminobutyric acid-B (GABA-B) receptor encephalitis also often shows such medial temporal hyperintensities but may additionally involve cerebellar lesions and atrophy. Gamma aminobutyric acid-A (GABA-A) receptor encephalitis features multifocal, confluent lesions in cortical and subcortical areas, sometimes leading to generalized atrophy. MRI is unremarkable in most patients with immunoglobulin-like cell adhesion molecule 5 (IgLON5)-disease, while individual case reports identified T2/FLAIR hyperintense lesions, diffusion restriction and atrophy in the brainstem, hippocampus and cerebellum. These findings highlight the need for MRI studies in patients with suspected autoimmune encephalitis to capture disease-specific changes and to exclude alternative diagnoses. Ideally, MRI investigations should be performed using dedicated autoimmune encephalitis imaging protocols. Longitudinal MRI studies play an important role to evaluate potential relapses and to manage long-term complications. Advanced MRI techniques and current research into imaging biomarkers will help to enhance the diagnostic accuracy of MRI investigations and individual patient outcome prediction. This will eventually enable better treatment decisions with improved clinical outcomes.
{"title":"MRI findings in autoimmune encephalitis","authors":"T.J. Hartung , F. Bartels , J. Kuchling , S. Krohn , J. Leidel , M. Mantwill , K. Wurdack , S. Yogeshwar , M. Scheel , C. Finke","doi":"10.1016/j.neurol.2024.08.006","DOIUrl":"10.1016/j.neurol.2024.08.006","url":null,"abstract":"<div><div>Autoimmune encephalitis encompasses a spectrum of conditions characterized by distinct clinical features and magnetic resonance imaging (MRI) findings. Here, we review the literature on acute MRI changes in the most common autoimmune encephalitis variants. In N-methyl-D-aspartate (NMDA) receptor encephalitis, most patients have a normal MRI in the acute stage. When lesions are present in the acute stage, they are typically subtle and non-specific white matter lesions that do not correspond with the clinical syndrome. In some NMDA receptor encephalitis cases, these T2-hyperintense lesions may be indicative of an NMDA receptor encephalitis overlap syndrome with simultaneous co-existence of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Encephalitis with leucine-rich glioma-inactivated 1 (LGI1)-, contactin-associated protein-like 2 (CASPR2)- or glutamic acid decarboxylase (GAD)- antibodies typically presents as limbic encephalitis (LE) with unilateral or bilateral T2/fluid attenuated inversion recovery (FLAIR) hyperintensities in the medial temporal lobe that can progress to hippocampal atrophy. Gamma aminobutyric acid-B (GABA-B) receptor encephalitis also often shows such medial temporal hyperintensities but may additionally involve cerebellar lesions and atrophy. Gamma aminobutyric acid-A (GABA-A) receptor encephalitis features multifocal, confluent lesions in cortical and subcortical areas, sometimes leading to generalized atrophy. MRI is unremarkable in most patients with immunoglobulin-like cell adhesion molecule 5 (IgLON5)-disease, while individual case reports identified T2/FLAIR hyperintense lesions, diffusion restriction and atrophy in the brainstem, hippocampus and cerebellum. These findings highlight the need for MRI studies in patients with suspected autoimmune encephalitis to capture disease-specific changes and to exclude alternative diagnoses. Ideally, MRI investigations should be performed using dedicated autoimmune encephalitis imaging protocols. Longitudinal MRI studies play an important role to evaluate potential relapses and to manage long-term complications. Advanced MRI techniques and current research into imaging biomarkers will help to enhance the diagnostic accuracy of MRI investigations and individual patient outcome prediction. This will eventually enable better treatment decisions with improved clinical outcomes.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 895-907"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366417","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.2024.08.009
S. Nitsch , R. Höftberger
Antibody-associated autoimmune neurological diseases are a group of disorders with various immune effector mechanisms that result in significant differences in disease course and prognosis. Paraneoplastic or idiopathic autoimmune encephalitis associated with antibodies against intracellular antigens are mostly characterized by a T-cell-dominated inflammation with neuronal loss, astrogliosis, and microglial nodules. In anti-Yo paraneoplastic cerebellar degeneration CD8+/granzymeB+ T cells were demonstrated in close apposition to neurons along with a nuclear upregulation of the activator of transcription 1, suggesting an important role of interferon-gamma in disease pathogenesis. Early and late disease stages may show different lesion types. For example, tissue samples from patients with temporal lobe epilepsy associated with antiglutamic acid decarboxylase 65 antibodies in early disease stages show numerous infiltrating T cells targeting hippocampal neurons and high numbers of B cells and plasma cells, while in chronic stages inflammation gets less and is followed by hippocampal sclerosis. Similarly, antiglial fibrillary acidic protein meningoencephalomyelitis may show loss of astrocytes only in the very early lesions, whereas in subacute and chronic stages astrocytes can get replenished most likely due to their high regeneration potential. In contrast, neuropathology of autoimmune neurological diseases mediated by surface antibodies is mostly characterized by a dysfunction of neurons in the absence of immune-mediated neuronal damage. The interaction of surface antibodies with their target antigen and the resulting downstream mechanisms are variable and can range from an internalization of the receptor in well-preserved neurons in anti-N-methyl-D-aspartate receptor encephalitis to an irreversible internalization and blocking of the receptor that may be associated with an accumulation of phosphorylated tau in specific brain regions in anti-IgLON5 disease. Interestingly, anti-IgLON5 patients with short disease duration were shown to present prominent deposition of IgG4 in the neuropil and on neuronal membranes in the absence of neuronal tau deposits, suggesting that the immune mechanisms precede neurodegeneration. Knowledge about pathomechanisms and patterns of tissue damage in different disease stages of antibody-associated autoimmune diseases will help to identify novel biomarkers and can give important clues for possible therapeutic interventions.
抗体相关自身免疫性神经疾病是一组具有不同免疫效应机制的疾病，这些机制导致了疾病过程和预后的显著差异。与细胞内抗原抗体相关的副肿瘤性或特发性自身免疫性脑炎大多以 T 细胞为主的炎症为特征，伴有神经元缺失、星形胶质细胞增生和小胶质细胞结节。在抗-Yo 副肿瘤性小脑变性中，CD8+/granzymeB+ T 细胞与神经元紧密结合，转录激活因子 1 核上调，这表明干扰素-γ 在疾病发病机制中起着重要作用。疾病的早期和晚期可能表现出不同的病变类型。例如，与抗谷氨酸脱羧酶 65 抗体相关的颞叶癫痫患者的组织样本在疾病早期阶段显示出大量以海马神经元为目标的浸润性 T 细胞以及大量 B 细胞和浆细胞，而在慢性阶段炎症会减轻，随后出现海马硬化。同样，抗胶质纤维酸性蛋白脑膜脑脊髓炎只有在病变早期才会出现星形胶质细胞丢失，而在亚急性和慢性阶段，星形胶质细胞很可能因其再生潜力大而得到补充。相比之下，由表面抗体介导的自身免疫性神经系统疾病的神经病理学特征主要是神经元功能障碍，而没有免疫介导的神经元损伤。表面抗体与其靶抗原的相互作用以及由此产生的下游机制是多变的，从抗N-甲基-D-天冬氨酸受体脑炎中保存完好的神经元的受体内化，到抗IgLON5疾病中不可逆的受体内化和阻断，这可能与磷酸化tau在特定脑区的积累有关。有趣的是，病程较短的抗IgLON5患者的神经髓鞘和神经元膜上有明显的IgG4沉积，而神经元tau沉积却不存在，这表明免疫机制先于神经变性。对抗体相关自身免疫性疾病不同疾病阶段的病理机制和组织损伤模式的了解将有助于确定新的生物标记物，并为可能的治疗干预提供重要线索。
{"title":"What we’ve learnt about autoimmune neurological diseases from neuropathology","authors":"S. Nitsch , R. Höftberger","doi":"10.1016/j.neurol.2024.08.009","DOIUrl":"10.1016/j.neurol.2024.08.009","url":null,"abstract":"<div><div>Antibody-associated autoimmune neurological diseases are a group of disorders with various immune effector mechanisms that result in significant differences in disease course and prognosis. Paraneoplastic or idiopathic autoimmune encephalitis associated with antibodies against intracellular antigens are mostly characterized by a T-cell-dominated inflammation with neuronal loss, astrogliosis, and microglial nodules. In anti-Yo paraneoplastic cerebellar degeneration CD8+/granzymeB+ T cells were demonstrated in close apposition to neurons along with a nuclear upregulation of the activator of transcription 1, suggesting an important role of interferon-gamma in disease pathogenesis. Early and late disease stages may show different lesion types. For example, tissue samples from patients with temporal lobe epilepsy associated with antiglutamic acid decarboxylase 65 antibodies in early disease stages show numerous infiltrating T cells targeting hippocampal neurons and high numbers of B cells and plasma cells, while in chronic stages inflammation gets less and is followed by hippocampal sclerosis. Similarly, antiglial fibrillary acidic protein meningoencephalomyelitis may show loss of astrocytes only in the very early lesions, whereas in subacute and chronic stages astrocytes can get replenished most likely due to their high regeneration potential. In contrast, neuropathology of autoimmune neurological diseases mediated by surface antibodies is mostly characterized by a dysfunction of neurons in the absence of immune-mediated neuronal damage. The interaction of surface antibodies with their target antigen and the resulting downstream mechanisms are variable and can range from an internalization of the receptor in well-preserved neurons in anti-N-methyl-D-aspartate receptor encephalitis to an irreversible internalization and blocking of the receptor that may be associated with an accumulation of phosphorylated tau in specific brain regions in anti-IgLON5 disease. Interestingly, anti-IgLON5 patients with short disease duration were shown to present prominent deposition of IgG4 in the neuropil and on neuronal membranes in the absence of neuronal tau deposits, suggesting that the immune mechanisms precede neurodegeneration. Knowledge about pathomechanisms and patterns of tissue damage in different disease stages of antibody-associated autoimmune diseases will help to identify novel biomarkers and can give important clues for possible therapeutic interventions.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 908-915"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353000","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.2024.07.005
R. Ursu , C. Belin , S. Cuzzubbo , A.F. Carpentier
Chimeric antigen receptor T-cell (CAR T-cell) therapies have emerged as a promising treatment modality for several malignancies, particularly haematological malignancies, by inducing robust antitumour responses. However, CAR T-cell therapies are associated with a spectrum of adverse events, including neurological complications. We here provide a review of neurological adverse events observed in patients undergoing CAR T-cell therapy, focusing on their incidence, clinical manifestations, underlying mechanisms and potential management strategies.
嵌合抗原受体 T 细胞（CAR T 细胞）疗法通过诱导强大的抗肿瘤反应，已成为治疗多种恶性肿瘤（尤其是血液系统恶性肿瘤）的一种前景广阔的治疗模式。然而，CAR T 细胞疗法与一系列不良事件有关，包括神经系统并发症。我们在此综述了在接受 CAR T 细胞疗法的患者中观察到的神经系统不良事件，重点关注其发生率、临床表现、潜在机制和潜在管理策略。
{"title":"CAR T-cell-associated neurotoxicity: A comprehensive review","authors":"R. Ursu , C. Belin , S. Cuzzubbo , A.F. Carpentier","doi":"10.1016/j.neurol.2024.07.005","DOIUrl":"10.1016/j.neurol.2024.07.005","url":null,"abstract":"<div><div>Chimeric antigen receptor T-cell (CAR T-cell) therapies have emerged as a promising treatment modality for several malignancies, particularly haematological malignancies, by inducing robust antitumour responses. However, CAR T-cell therapies are associated with a spectrum of adverse events, including neurological complications. We here provide a review of neurological adverse events observed in patients undergoing CAR T-cell therapy, focusing on their incidence, clinical manifestations, underlying mechanisms and potential management strategies.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 989-994"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256855","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.2024.07.004
C. Gaig , L. Sabater
Anti-IgLON5 disease is a rare neurological disease, identified just ten years ago, where autoimmunity and neurodegeneration converge. The heterogeneity of symptoms, sometimes mimicking pure neurodegenerative diseases or motor neuron diseases, in addition to lack of awareness, represents a diagnostic challenge. Biomarkers of neuronal damage in combination with in vivo visualization of tau deposition using positron emission tomography (PET) scanning could represent a major advance in monitoring disease progression. Recent studies with more autopsies available have helped refine the knowledge of the pathological features of the disease and strengthen the autoimmune hypothesis of the disease. Although the pathogenesis of anti-IgLON5 disease remains unclear, the irreversible antibody-mediated decrease of IgLON5 clusters from the cell surface and alterations produced in the cytoskeleton, as well as the behavioural abnormalities and signs of neuroinflammation and neurodegeneration observed in the brains of animals infused with antibodies from patients by passive transfer, which have recently been published, support the autoimmune hypothesis of the disease. This review aims to summarize these important aspects and recent advances in the pathophysiology of anti-IgLON5 disease.
抗 IgLON5 病是一种罕见的神经系统疾病，十年前才被发现，是自身免疫和神经变性的结合。这种疾病的症状多种多样，有时会模仿纯粹的神经退行性疾病或运动神经元疾病，再加上人们对这种疾病缺乏认识，因此给诊断带来了挑战。神经元损伤的生物标志物与正电子发射断层扫描（PET）对 tau 沉积的活体可视化相结合，可在监测疾病进展方面取得重大进展。最近的研究获得了更多的尸体解剖，有助于完善对该病病理特征的认识，并加强了该病的自身免疫假说。尽管抗 IgLON5 病的发病机制仍不清楚，但最近发表的研究结果表明，抗体介导的细胞表面 IgLON5 簇的不可逆减少和细胞骨架的改变，以及在通过被动转移输注患者抗体的动物大脑中观察到的行为异常、神经炎症和神经变性迹象，都支持该病的自身免疫假说。本综述旨在总结抗IgLON5疾病病理生理学的这些重要方面和最新进展。
{"title":"Clinical presentations and antibody mechanisms in anti-IgLON5 disease","authors":"C. Gaig , L. Sabater","doi":"10.1016/j.neurol.2024.07.004","DOIUrl":"10.1016/j.neurol.2024.07.004","url":null,"abstract":"<div><div>Anti-IgLON5 disease is a rare neurological disease, identified just ten years ago, where autoimmunity and neurodegeneration converge. The heterogeneity of symptoms, sometimes mimicking pure neurodegenerative diseases or motor neuron diseases, in addition to lack of awareness, represents a diagnostic challenge. Biomarkers of neuronal damage in combination with in vivo visualization of tau deposition using positron emission tomography (PET) scanning could represent a major advance in monitoring disease progression. Recent studies with more autopsies available have helped refine the knowledge of the pathological features of the disease and strengthen the autoimmune hypothesis of the disease. Although the pathogenesis of anti-IgLON5 disease remains unclear, the irreversible antibody-mediated decrease of IgLON5 clusters from the cell surface and alterations produced in the cytoskeleton, as well as the behavioural abnormalities and signs of neuroinflammation and neurodegeneration observed in the brains of animals infused with antibodies from patients by passive transfer, which have recently been published, support the autoimmune hypothesis of the disease. This review aims to summarize these important aspects and recent advances in the pathophysiology of anti-IgLON5 disease.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 940-949"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294303","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.2024.08.005
F. Leypoldt
There is a need to improve therapies in autoimmune neurologic conditions. Yet which strategic objectives are required, what are the barriers that stand before reaching them, and what are the options to address them? This article tries to summarize these objectives and their respective barriers. It discusses the difficulties in identifying molecular targets, biomarker-defined subgroups, the merits of upstream and downstream-targeted therapies, the need to develop autoreactivity-specific treatments in contrast to cell-type specific therapies, and the “evidence-bottleneck”. Its focus is on autoantigen-specific autoimmunopathies in neurology. It also discusses the role of B- and T-cells in autoimmune neurology and how these can be exploited therapeutically. Finally, it argues for improved training of present and future neuroimmunologists.
需要改进自身免疫性神经疾病的疗法。然而，需要实现哪些战略目标，在实现这些目标之前存在哪些障碍，又有哪些方案可以解决这些问题？本文试图总结这些目标及其各自的障碍。文章讨论了确定分子靶点的困难、生物标志物定义的亚组、上游和下游靶向疗法的优点、开发自身活性特异性疗法而非细胞类型特异性疗法的必要性以及 "证据瓶颈"。报告的重点是神经病学中的自身抗原特异性自身免疫病。报告还讨论了 B 细胞和 T 细胞在自身免疫性神经病学中的作用，以及如何利用这些细胞进行治疗。最后，该书主张加强对现在和未来神经免疫学家的培训。
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Pub Date : 2024-11-01DOI: 10.1016/j.neurol.2024.09.003
O. Benveniste
The discovery, over the last forty years or so, of specific myositis auto-antibodies (easily dosed in routine nowadays) and the fine clinically and pathologically phenotypic descriptions of affected patients have made it possible to review the classification of inflammatory myopathies. The arrival of “omic” techniques has also led to the discovery of different pathophysiological mechanisms among these different subgroups of myositis. Naturally, therapeutic approaches specifically targeting the representative abnormal pathways of each subgroup are being evaluated. This modern approach to myositis, which is clinical, pathophysiological, and therapeutic in the making, is presented in this review article.
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