Revue neurologique最新文献

{"title":"Mechanisms of immune tolerance breakdown in paraneoplastic neurological syndromes","authors":"E. Peter ,&nbsp;P. Dumez ,&nbsp;J. Honnorat ,&nbsp;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}

{"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}

{"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}

{"title":"MRI findings in autoimmune encephalitis","authors":"T.J. Hartung ,&nbsp;F. Bartels ,&nbsp;J. Kuchling ,&nbsp;S. Krohn ,&nbsp;J. Leidel ,&nbsp;M. Mantwill ,&nbsp;K. Wurdack ,&nbsp;S. Yogeshwar ,&nbsp;M. Scheel ,&nbsp;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}

{"title":"What we’ve learnt about autoimmune neurological diseases from neuropathology","authors":"S. Nitsch ,&nbsp;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}

{"title":"CAR T-cell-associated neurotoxicity: A comprehensive review","authors":"R. Ursu ,&nbsp;C. Belin ,&nbsp;S. Cuzzubbo ,&nbsp;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}

{"title":"Clinical presentations and antibody mechanisms in anti-IgLON5 disease","authors":"C. Gaig ,&nbsp;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}

{"title":"Strategies to improve autoimmune neurological diseases treatment","authors":"F. Leypoldt","doi":"10.1016/j.neurol.2024.08.005","DOIUrl":"10.1016/j.neurol.2024.08.005","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 888-894"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294307","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}

{"title":"Inflammatory myopathies in 2024: Better classify them to better treat them","authors":"O. Benveniste","doi":"10.1016/j.neurol.2024.09.003","DOIUrl":"10.1016/j.neurol.2024.09.003","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 963-970"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352998","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}

{"title":"The neurobiology and immunology of CASPR2-associated neurological disorders","authors":"B. Joubert","doi":"10.1016/j.neurol.2024.09.005","DOIUrl":"10.1016/j.neurol.2024.09.005","url":null,"abstract":"<div><div>CASPR2-associated neurological disorders encompass a wide clinical spectrum broadly divided into overlapping three autoimmune syndromes: CASPR2 limbic encephalitis, Morvan syndrome, and Isaacs syndrome. CASPR2 is a neuronal protein expressed at different sites in the central and peripheral nervous system and has a variety of roles and functions regarding neuronal excitability, synaptic plasticity, and homeostasis of inhibitory networks, most of which are only partially understood. CASPR2 antibodies have various pathogenic effects including internalization of CASPR2, disruption of protein-protein interactions, and, possibly, complement activation. Their pathogenic effect is well demonstrated in the limbic encephalitis phenotype, but the role of pathogenic antibodies in the development of other clinical manifestations is less clear. CASPR2 limbic encephalitis also differ from the other CASPR2-associated disorders in regard to HLA allele and paraneoplastic associations, suggesting it has immunological mechanisms distinct from the other clinical forms. Future studies are needed to better understand how the immunological alterations lead to the different phenotypes associated with CASPR2 antibodies.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"180 9","pages":"Pages 950-956"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352999","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}