Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Anti-IgLON5 Disease 10 Years Later: What We Know and What We Do Not Know.","authors":"Francesc Graus, Lidia Sabater, Carles Gaig, Ellen Gelpi, Alex Iranzo, Josep O Dalmau, Joan Santamaria","doi":"10.1212/NXI.0000000000200353","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200353","url":null,"abstract":"<p><p>Anti-IgLON5 disease was identified 10 years ago, thanks to the discovery of IgLON5 antibodies and the joint effort of specialists in sleep medicine, neuroimmunology, and neuropathology. Without this collaboration, it would have been impossible to untangle fundamental aspects of this disease. After the seminal description in 2014, today there is growing evidence that most patients present a chronic progressive course with gait instability, abnormal movements, bulbar dysfunction, and a sleep disorder characterized by nonrapid eye movement and REM parasomnias, and obstructive sleep apnea with stridor. Unlike other autoimmune encephalitides, the response to immunotherapy is suboptimal. Neuropathologic studies in patients with a prolonged clinical course showed a novel 3-repeat and 4-repeat neuronal tauopathy mainly involving the hypothalamus and tegmentum of the brainstem. The absence of tau deposits in the brain of patients who died early, the demonstration that IgLON5 antibodies cause an irreversible decrease in cell-surface levels of IgLON5, and a disorganization of the neuronal cytoskeleton suggest that the disease is primarily autoimmune and the tauopathy a secondary event. After a decade, we now know the disease much better, but important issues still need to be addressed. We have to gather more information on the natural course of the disease, develop better treatments, and identify robust predictors of outcome. More basic research is needed on the physiology of IgLON5, how antibodies disrupt its function, and the downstream effects leading to neurodegeneration. Finally, better designed passive transfer and active immunization models are needed to confirm the pathogenic effect of IgLON5 antibodies.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200353"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selected Aspects of the Neuroimmunology of Cell Therapies for Neurologic Disease: Perspective.","authors":"Richard M Ransohoff","doi":"10.1212/NXI.0000000000200352","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200352","url":null,"abstract":"<p><p>Neurologic disease remains a cause of incalculable suffering, a formidable public health burden, and a wilderness of complex biology and medicine. At the same time, advances in basic science, technology, and the clinical development toolkit bring meaningful benefit for patients along with realistic hope for those whose conditions remain inadequately treated. This perspective focuses on cell-based therapies for neurologic disease, with particular emphasis on neuroimmunologic disorders and on the immunologic considerations of cell therapy for nonimmune conditions. I will consider the use of chimeric antigen receptor (CAR)-T effector cells and regulatory T-cell therapies for autoimmune conditions. I will briefly discuss the immune aspects of pluripotent stem cell (PSC)-derived neuronal therapies. With apologies for the omission, we do not discuss mesenchymal stem cells, glial progenitor cells, or CAR-NK cells, primarily for space limitations.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200352"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies Against Dihydrolipoamide S-Acetyltransferase Are Not Associated With Immune-Mediated Neuropathies.","authors":"Alexandre Jentzer, Jérémie El-Bechir, Guillaume Taieb, Jérôme J Devaux","doi":"10.1212/NXI.0000000000200336","DOIUrl":"10.1212/NXI.0000000000200336","url":null,"abstract":"<p><strong>Objectives: </strong>Dihydrolipoamide S-acetyltransferase (DLAT), the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC-E2), has recently been suggested to be a biomarker of chronic inflammatory demyelinating polyneuropathy (CIDP). It was particularly associated with sensory variants of CIDP. Antimitochondrial antibodies are important for the diagnosis of primary biliary cholangitis, but insofar, only 2 studies have reported an association with CIDP. Here, we aimed to validate these observations in a cohort of French patients with immune-mediated neuropathy.</p><p><strong>Methods: </strong>The positivity against PDC-E2/DLAT was examined using ELISA and confirmed using commercially available immuno-DOT and by indirect immunofluorescence on stomach, kidney, and liver sections.</p><p><strong>Results: </strong>None of the 20 healthy controls, 31 patients with Guillain-Barré syndrome, 102 patients with CIDP (including 24 patients with sensory CIDP), 26 patients with monoclonal gammopathy, 23 patients with Charcot-Marie-Tooth disease, or 20 patients with autoimmune nodopathy showed IgG against PDC-E2/DLAT.</p><p><strong>Discussion: </strong>PDC-E2/DLAT is accurately a target antigen in immune-mediated neuropathies.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200336"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broad Analysis of Serum and Intrathecal Antimicrobial Antibodies in Multiple Sclerosis Underscores Unique Role of Epstein-Barr Virus.","authors":"Florence Pache, Carolin Otto, Diana Wilken, Tatjana Lietzow, Katja Steinhagen, Evelin Grage-Griebenow, Patrick Schindler, Moritz Niederschweiberer, Brigitte Wildemann, Sven Jarius, Klemens Ruprecht","doi":"10.1212/NXI.0000000000200332","DOIUrl":"10.1212/NXI.0000000000200332","url":null,"abstract":"<p><strong>Background and objectives: </strong>There is a strong link between Epstein-Barr virus (EBV) and multiple sclerosis (MS), but the underlying mechanisms are unclear. Patients with MS typically have a polyspecific intrathecal production of immunoglobulin G (IgG), part of which is directed against various microbial antigens. In this study, we comprehensively analyzed seroprevalences and frequencies of an intrathecal IgG production to EBV compared with 10 other common microbes in patients with MS.</p><p><strong>Methods: </strong>Antibodies to EBV and to <i>Borrelia burgdorferi</i>, cytomegalovirus, herpes simplex virus type 1/2, measles virus, mumps virus, rubella virus, parvovirus B19, tick-borne encephalitis virus, <i>Toxoplasma gondii</i>, and varicella zoster virus (VZV) were determined in stored paired CSF and serum samples of 50 patients with MS. Intrathecal antimicrobial antibody production was assessed by calculating antibody indices (AIs) according to standard formula.</p><p><strong>Results: </strong>While 50 (100%) of 50 patients with MS were EBV seropositive, seroprevalences of all other 10 microbes were lower, ranging from 94% (VZV) to 6% (<i>Borrelia burgdorferi</i>). An intrathecal production of antimicrobial antibodies was detected in 102 (28%) of 370 AI determinations of patients who were seropositive to the respective antimicrobial antibodies but was practically absent in seronegative patients (2/187 [1%], <i>p</i> < 0.0001). The frequency of intrathecally produced antimicrobial antibodies among patients who were seropositive for the respective antibodies was roughly 40% for measles, rubella, mumps, and VZV and 70% for parvovirus B19. By contrast, the frequency of intrathecally produced EBV antibodies was low (10%) and, when related to their respective seroprevalences, lower than those of all other investigated microbes.</p><p><strong>Discussion: </strong>Despite the universal EBV seroprevalence, the frequency of intrathecally produced EBV antibodies in patients with MS is lower than that of other microbes, whose seroprevalences are lower than those of EBV. This seemingly paradoxical finding underscores the unique role of EBV in MS and could be explained by the hypothesis that B lineage cells responsible for intrathecal antibody production are primed during and through acute EBV infection to enter the CNS of patients with MS, that is, at a time point when EBV antibody-producing cells have not yet been generated and, therefore, are not yet available for entering the CNS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200332"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Reported Outcome Measures in NMDA Receptor Encephalitis.","authors":"Josephine Heine, Ole Jonas Boeken, Sophia Rekers, Katharina Wurdack, Harald Prüss, Carsten Finke","doi":"10.1212/NXI.0000000000200343","DOIUrl":"10.1212/NXI.0000000000200343","url":null,"abstract":"<p><strong>Background and objectives: </strong>The characteristics of persistent long-term symptoms and their contribution to subjective quality of life remain unclear in patients with NMDAR encephalitis. In this study, we aimed to evaluate postacute neuropsychiatric symptoms, subjective cognitive complaints, and disease coping mechanisms and identify predictors of health-related quality of life (HRQoL) after N-methyl-D-aspartate receptor (NMDAR) encephalitis.</p><p><strong>Methods: </strong>This cross-sectional observational study investigated patients with NMDAR encephalitis in the postacute phase. Psychometric scales included assessment of neuropsychiatric symptoms (i.e., fatigue, sleep, anxiety, and depressive symptoms), HRQoL, everyday independence, metamemory (i.e., self-rated ability, satisfaction, and use of strategies), and coping strategies (i.e., self-efficacy, disease-related coping, and stress management).</p><p><strong>Results: </strong>A total of 50 patients (mean age 26.0 ± 10.1 years, 86% female) participated at a median of 4.15 (range 0.3-30.3) years after symptom onset. Patients reported significantly increased levels of anxiety (Beck Anxiety Inventory: 10.5 ± 7.7 [mean ± SD], 95% CI [8.32-12.71], <i>p</i> < 0.001) and depressive (Beck Depression Inventory-II: 11.4 ± 7.7 [9.22-13.62], <i>p</i> = 0.001) symptoms compared with the normative population. Both sleep problems (Pittsburgh Sleep Quality Index: 5.8 ± 3.0 [4.98-6.66], <i>p</i> < 0.001) and motor and cognitive fatigue (Fatigue Scale for Motor and Cognitive Function: 50.5 ± 23.1 [42.5-58.4], <i>p</i> < 0.001) were significantly more prevalent. Moreover, lower self-rated memory ability (Multifactorial Memory Questionnaire score: 54.6 ± 8.5 [52.1-57.1], <i>p</i> = 0.004) was associated with greater reliance on compensatory strategies and memory aids (<i>r</i> = -0.41, <i>p</i> = 0.004). Patients used significantly fewer cognitive coping strategies, such as relativization (11.7 ± 4.7 [10.3-13.1], <i>p</i> = 0.001), while depressive coping prevailed (49.1 ± 15.5 [44.5-53.8], <i>p</i> < 0.001). It is important to note that HRQoL was predicted by self-reported affective symptoms, self-efficacy, and coping behaviors in multivariable regression analyses, but not by acute disease severity or postacute physical disability.</p><p><strong>Discussion: </strong>Our findings show that persistent neuropsychiatric and subjective cognitive concerns explain a large part of the reduced quality of life in patients with NMDAR encephalitis. These findings have important implications for a patient-centered postacute care and the role of disease coping strategies in the neurorehabilitation of autoimmune encephalitis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200343"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Discovery of Autoimmune Nodopathies and the Impact of IgG4 Antibodies in Autoimmune Neurology.","authors":"Luis Querol, Marinos C Dalakas","doi":"10.1212/NXI.0000000000200365","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200365","url":null,"abstract":"<p><p>In the past decade, significant progress has been made on the understanding of IgG4-mediated autoimmune diseases, of both the central and the peripheral CNS. In addition to the description of diverse antigenic targets, the description of IgG subclasses associated with specific pathogenic autoantibodies has provided useful insights into the pathophysiology and, more importantly, into the therapeutic implications of the autoantibody subclasses. This understanding has affected how myasthenia gravis, autoimmune encephalitis, and autoimmune neuropathies are treated. In the case of autoimmune neuropathies, the discovery of antigenic targets located at the node of Ranvier has led to the definition of a new diagnostic category, the autoimmune nodopathies, which differentiate them from the classical forms of Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. These neuropathies including those caused by autoantibodies targeting contactin-1, contactin-associated protein 1, and neurofascin are mainly, though not always exclusively, mediated by IgG4 antibodies, and respond to therapies similarly to other IgG4-mediated neurologic and non-neurologic diseases, providing evidence that not only the antigenic target but also the autoantibody subclass play a role in understanding both the disease pathophysiology and response to therapies. In this article, we describe the history and main findings on autoimmune nodopathies; highlight the particularities and similarities of IgG4-mediated neurologic diseases, including autoimmune nodopathies and neuromuscular junction and certain CNS disorders; elaborate on the unique functional properties of IgG4 in influencing their specific response to immunotherapies stressing the rationale of the most suitable present and future targeted therapies; and discuss how best to apply and monitor maintenance therapies for inducing disease stability in all IgG4 neurologic autoimmunities including the need for potential future biomarkers.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200365"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro-RNA Signature in CSF Before and After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis.","authors":"Ivan Pavlovic, Fredrik Axling, Faisal Hayat Nazir, Malin Müller, Anna Wiberg, Joachim Burman","doi":"10.1212/NXI.0000000000200345","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200345","url":null,"abstract":"<p><strong>Background and objectives: </strong>MicroRNAs (miRNAs) are regulators of gene expression and have been reported to be dysregulated in people with multiple sclerosis (pwMS). Autologous hematopoietic stem cell transplantation (aHSCT) is an immune-ablative treatment intervention for pwMS. Currently, it is unknown if aHSCT affects expression levels of miRNAs in CSF. We explored the ability of circulating miRNA to discriminate between pwMS and healthy controls (HCs) and investigated whether these miRNAs were affected by treatment with aHSCT.</p><p><strong>Methods: </strong>Using quantitative reverse transcription PCR, 87 miRNAs were analyzed in CSF samples of a discovery cohort (<i>baseline: 4 & HC: 4</i>). The top 22 miRNAs discriminating between pwMS and HCs were then analyzed in 187 CSF samples of a validation cohort (<i>pwMS: 50, HC: 32</i>). Samples, failing quality control or being follow-ups to baseline samples with quality control issues, were excluded from further analyses. The remaining 133 samples (<i>HC: 29, MS: baseline: 33, 1 year: 30, 2 years: 26, 3-5 years: 15</i>) were analyzed for expression of the top 22 miRNAs.</p><p><strong>Results: </strong>Twelve miRNAs were dysregulated in pwMS compared with HC (<i>q</i> < 0.05). Associations with clinical and analytical parameters were observed in relation to all 12 miRNAs; however, a cluster of 4 miRNAs (miR-16-5p, miR-21-5p, miR-150-5p, and miR-146a-5p) with strong correlations (<i>r</i> > 0.60, <i>p</i> < 0.001) with multiple parameters was identified. Of the 12 miRNAs, 8 were differentially expressed in pwMS with gadolinium-enhancing lesions at baseline and 4 by prior disease-modifying treatment class (<i>p</i> < 0.05). These 4 miRNAs correlated strongly with each other, decreased after aHSCT, and remained low throughout the follow-up period (<i>p</i> < 0.05). Target and pathway analysis of these revealed association with biological processes affecting cytokine production, inflammatory response, and regulation of myelin maintenance.</p><p><strong>Discussion: </strong>miRNAs are dysregulated in CSF from pwMS and particularly in patients with less effective treatments and/or higher inflammatory disease activity. A 4-miRNA signature with elevated expression of miR-16-5p, miR-21-5p, miR-150-5p, and miR-146a-5p was recurring in multiple analyses. After intervention with aHSCT, the expression levels approached the levels of the HCs, suggesting a potent treatment effect.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200345"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrum of Clinical and Imaging Features of Children With GFAP Astrocytopathy.","authors":"Simon Sommer, Andreas Panzer, Annikki Bertolini, Robert Cleaveland, Vivek Jain, Tugba Kapanci, Ute Derichs, Tobias Geis, Axel Neu, Christa Löhr-Nilles, Rahel Aeschimann-Huhn, Marina Flotats-Bastardas, Kumaran Deiva, Thais Armangue, Gemma Olivé-Cirera, Sudheeran Kannoth, Anne Koy, Hadas Meirson, Aviva Fattal-Valevski, Esther Ganelin-Cohen, Heike Losch, Annacarin Horne, Ronny Wickström, Justina Dargvainiene, Frank Leypoldt, Kevin Rostasy","doi":"10.1212/NXI.0000000000200327","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200327","url":null,"abstract":"<p><strong>Background and objectives: </strong>Glial fibrillary acidic protein (GFAP) antibodies (abs) have been described primarily in adults with a spectrum of autoimmune-mediated diseases. In children, data on clinical and neuroradiologic features of children with autoimmune GFAP astrocytopathy are limited. The aim of this study was to describe the clinical and radiologic features in children with GFAP-ab-associated diseases.</p><p><strong>Methods: </strong>We retrospectively recruited children from 13 clinical centers between 2020 and 2023 who (1) tested positive for GFAP-ab in serum and/or CSF and (2) of whom a complete clinical and MRI data set was available.</p><p><strong>Results: </strong>We identified and included 15 children (5 girls, 10 boys). The median age at onset was 9.9 years (range: 2-16 years). All children presented with features of AE or meningitis, acute cerebellitis, or transverse myelitis. CSF pleocytosis was common (13/15, median 245 cells/μL), and 13 (87%) of 15 harbored GFAP-abs in their CSF, 8 (53%) of whom did not have detectable GFAP-abs in their serum. MRI was abnormal in 15 (100%) of 15 children: Specific patterns included confluent lesions in the pons or caudate nucleus (11/15; 73%), peri-aqueductal regions (13/15; 87%), and spinal cord (6/10; 60%). 12 children had a favorable outcome (mRS score of </= 1). Two patients died in the acute phase or during follow-up.</p><p><strong>Discussion: </strong>GFAP-ab-associated diseases encompass a wide spectrum of clinical presentation associated with a particular set of MRI features clearly distinct to other antibody-mediated diseases or MOGAD. We recommend that testing for GFAP-abs in serum and CSF be included in the workup of children with AE, particularly if brainstem involvement occurs.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200327"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric MOG-Ab-Associated Encephalitis: Supporting Early Recognition and Treatment.","authors":"Nee Na Kim, Dimitrios Champsas, Michael Eyre, Omar Abdel-Mannan, Vanessa Lee, Alison Skippen, Manali V Chitre, Rob Forsyth, Cheryl Hemingway, Rachel Kneen, Ming Lim, Dipak Ram, Sithara Ramdas, Evangeline Wassmer, Siobhan West, Sukhvir Wright, Asthik Biswas, Kshitij Mankad, Eoin P Flanagan, Jacqueline Palace, Thomas Rossor, Olga Ciccarelli, Yael Hacohen","doi":"10.1212/NXI.0000000000200323","DOIUrl":"10.1212/NXI.0000000000200323","url":null,"abstract":"<p><strong>Background and objectives: </strong>Antibodies to myelin oligodendrocyte glycoprotein (MOG-Ab) have recently been reported in patients with encephalitis who do not fulfill criteria for acute disseminated encephalomyelitis (ADEM). We evaluated a cohort of these children and compared them with children with ADEM.</p><p><strong>Methods: </strong>This retrospective, multicenter cohort study comprised consecutive patients <18 years of age with MOG-Ab who fulfilled criteria for autoimmune encephalitis. These patients were stratified into (1) children not fulfilling criteria for ADEM (encephalitis phenotype) and (2) children with ADEM. Clinical/paraclinical data were extracted from the electronic records. Comparisons were made using the Mann-Whitney <i>U</i> test and χ² Fisher exact test for statistical analysis.</p><p><strong>Results: </strong>From 235 patients with positive MOG-Ab, we identified 33 (14%) with encephalitis and 74 (31%) with ADEM. The most common presenting symptoms in children with encephalitis were headache (88%), seizures (73%), and fever (67%). Infective meningoencephalitis was the initial diagnosis in 67%. CSF pleocytosis was seen in 79%. Initial MRI brain was normal in 8/33 (24%) patients. When abnormal, multifocal cortical changes were seen in 66% and unilateral cortical changes in 18%. Restricted diffusion was demonstrated in 43%. Intra-attack new lesions were seen in 7/13 (54%). When comparing with children with ADEM, children with encephalitis were older (median 8.9 vs 5.7 years, <i>p</i> = 0.005), were more likely to be admitted to intensive care (14/34 vs 4/74, <i>p</i> < 0.0001), were given steroid later (median 16.6 vs 9.6 days, <i>p</i> = 0.04), and were more likely to be diagnosed with epilepsy at last follow-up (6/33 vs 1/74, <i>p</i> = 0.003).</p><p><strong>Discussion: </strong>MOG-Ab should be tested in all patients with suspected encephalitis even in the context of initially normal brain MRI. Although exclusion of infections should be part of the diagnostic process of any child with encephalitis, in immunocompetent children, when herpes simplex virus CSF PCR and gram stains are negative, these features do not preclude the diagnosis of immune mediated disease and should not delay initiation of first-line immunosuppression (steroids, IVIG, plasma exchange), even while awaiting the antibody results.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 6","pages":"e200323"},"PeriodicalIF":7.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Pharmacodynamics of Natalizumab 6-Week Dosing vs Continued 4-Week Dosing for Relapsing-Remitting Multiple Sclerosis.","authors":"John F Foley, Gilles Defer, Lana Zhovtis Ryerson, Jeffrey A Cohen, Douglas L Arnold, Helmut Butzkueven, Gary R Cutter, Gavin Giovannoni, Joep Killestein, Heinz Wiendl, Kexuan Li, Liesel Dsilva, Marie Toukam, Kyle Ferber, Jihee Sohn, Holly Engelman, Tyler Lasky","doi":"10.1212/NXI.0000000000200321","DOIUrl":"10.1212/NXI.0000000000200321","url":null,"abstract":"<p><strong>Background and objectives: </strong>Exposure to natalizumab, an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS), is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Compared with every-4-week (Q4W) dosing, extended-interval dosing of natalizumab is associated with decreased risk of PML. Clinical efficacy was maintained in the majority of patients switched to every-6-week (Q6W) dosing in the phase 3b NOVA clinical trial. In this article, we report pharmacokinetics (PK) and pharmacodynamics (PD) of Q6W vs Q4W dosing in NOVA.</p><p><strong>Methods: </strong>In NOVA study Part 1, participants with RRMS (aged 18-60 years) and Expanded Disability Status Scale score <5.5, who were stable on IV natalizumab Q4W dosing for ≥12 months, were randomized to continue IV Q4W dosing or switched to IV Q6W dosing of natalizumab and followed for 72 weeks. Exploratory outcomes were measurements of trough serum natalizumab concentration, α4-integrin saturation, and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration. A mixed model of repeated measures was used to estimate mean treatment differences between groups. Patient-level PK and PD data were examined in those with relapse or radiologic disease activity.</p><p><strong>Results: </strong>In NOVA, 486 (Q6W, n = 245; Q4W, n = 241) and 487 (Q6W, n = 246; Q4W, n = 241) participants were included in the PK and PD populations, respectively. Mean trough natalizumab concentrations ranged from 10 to 21 μg/mL (Q6W) and 33-38 μg/mL (Q4W), and mean α4-integrin saturation remained above 65.5% (Q6W) and above 77.9% (Q4W). In the Q6W group, mean sVCAM-1 levels increased 23.6% by week 24 and remained elevated throughout the study, while mean sVCAM-1 levels remained generally stable in the Q4W group. Most participants with T2 lesion activity or relapse activity, in either treatment arm, maintained trough natalizumab levels >10 μg/mL and trough α4-integrin saturation >50%.</p><p><strong>Discussion: </strong>Compared with Q4W dosing, Q6W dosing was associated with a 60%-70% decrease in mean trough natalizumab levels and a 9%-16% decrease in mean α4-integrin saturation. At the patient level, neither natalizumab concentration nor α4-integrin saturation was consistently predictive of lesion or relapse activity, suggesting that trough natalizumab and α4-integrin saturation measurements should be interpreted with caution in clinical practice.</p><p><strong>Trial registration information: </strong>ClinicalTrials.gov, NCT03689972; EudraCT, 2018-002145-11. Submitted 2018-09-27. First patient enrolled: 2018-12-26. https://clinicaltrials.gov/study/NCT03689972.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 6","pages":"e200321"},"PeriodicalIF":7.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}