Clinical and Experimental Neuroimmunology最新文献

{"title":"Neuroinflammation and neuroimmunology in Alzheimer's disease: The role of T-lymphocytes in Alzheimer's disease","authors":"Norio Chihara,&nbsp;Asato Tsuji,&nbsp;Riki Matsumoto","doi":"10.1111/cen3.12747","DOIUrl":"10.1111/cen3.12747","url":null,"abstract":"<p>Alzheimer's disease (AD) is the leading cause of dementia, with the number of patients with AD expected to double in the next quarter-century. Brain deposition of amyloid-β (Aβ) and tau proteins is a necessary but insufficient condition for AD pathogenesis. There is also growing evidence to suggest that chronic neuroinflammation due to excessive microglial activation and astrocyte dysfunction exacerbates the pathophysiology of AD, but the factors that disrupt these homeostatic processes remain unclear. Research into AD pathophysiology has shown interest in the changes in adaptive T-cells, which play a pivotal role in immunity. The immune alterations in the peripheral circulation and increased blood–brain-barrier permeability observed in patients with AD, even in the initial stages of the disease, require investigation of the immune mechanisms resulting from T-cell infiltration into the central nervous system (CNS) during disease initiation and exacerbation. Since T-cells play a two-faceted role in the CNS immune response, including pathogenic and neuroprotective roles, the role of T-cells in AD has been debated. Memory T-cells reside in the brain and communicate with glial cells and neurons. In this review, the role of immune responses in AD is discussed, focusing on the contribution of T-cells.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43294682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cotard syndrome in anti-adenylate kinase 5 autoantibodies limbic encephalitis","authors":"Aldo F. Costa,&nbsp;Alba Rodríguez","doi":"10.1111/cen3.12746","DOIUrl":"10.1111/cen3.12746","url":null,"abstract":"Cotard syndrome (CS) has been reported in patients with anti-N-methyl-D-Aspartate receptor (NMDAr) autoantibodies encephalitis, but not in limbic encephalitis (LE) associated with other autoantibodies. Clinical features of LE associated with autoantibodies against adenyl kinase 5 (AK5), a specific nucleoside monophosphate kinase of the central nervous system with crucial metabolic functions, have been previously reported in the literature. However, this is the first case reporting CS as one of the psychiatric symptoms during the clinical course. A right-handed 83-year-old woman developed memory problems, disorientation, behavioral changes and visual hallucinations in the past 2 months. Over the next 4 weeks, her symptoms progressed to a more marked deterioration of spatial orientation that interfered with daily activities and hobbies. In the following 4 weeks, she started to deny the existence of her head and occasionally she referred to herself as being dead. Neurological examination showed disorientation and anterograde amnesia. The Montreal Cognitive Assessment Scale score was 12 out of 30. Anterograde memory, attention, orientation and visuospatial/executive functions were predominately affected, whereas language and abstraction domains were spared. Routine laboratory examinations were within normal limits and infectious diseases of the central nervous system were ruled out. Cerebral spinal fluid showed lymphocytic pleocytosis (34 cells/mm, 58% lymphocytes), and hyperproteinorrachia (880 mg/L), with no presence of oligoclonal bands. Standard LE autoimmunity screening in cerebral spinal fluid was negative, including anti-NMDAR autoantibodies. A cerebral spinal fluid sample was sent to a specialized neuroimmunology laboratory for further analysis. Indirect immunofluorescence on a mouse tissue composite (TIF) showed positive anti-AK5 antibodies that were later confirmed by a cell-based assay carried out on human embryonic kidney 293 transfected cells. No other autoantibodies were positive. Brain magnetic resonance imaging showed bilateral hyperintensities in the mesial temporal lobes. The electroencephalogram and body positron emission computed tomography were unremarkable. The patient received 5-day intravenous immunoglobulin in combination with intravenous methylprednisolone (1 g/day). Over the next 3 months, the clinical course was unfavorable, and she underwent two cycles of rituximab. Cotard delusion persisted despite treatment with high doses of quetiapine. To the best of our knowledge, there are 30 reported cases of LE associated with anti-AK5 antibodies, and the present case is the first to report CS as a part of the clinical features. As in this case, patients with anti-AK5 encephalitis usually present a particularly unsatisfactory response to immunotherapy. Among the reported cases, most of the patients developed dementia due to rapidly progressive memory deficits, and approximately 50% of patients developed hippocampal atrophy. It mig","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42833164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A thank you note to our reviewers","authors":"","doi":"10.1111/cen3.12741","DOIUrl":"10.1111/cen3.12741","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42763966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 34th Annual Meeting of the Japanese Society for Neuroimmunology (JSNI)","authors":"","doi":"10.1111/cen3.12738","DOIUrl":"https://doi.org/10.1111/cen3.12738","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50133855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of clinical research on myasthenia gravis: Present and prospective view from Japan","authors":"Hiroyuki Murai","doi":"10.1111/cen3.12740","DOIUrl":"10.1111/cen3.12740","url":null,"abstract":"The clinical scene of myasthenia gravis (MG) is drastically changing. First, the number of patients is increasing. The epidemiological survey carried out in 2018 showed that the prevalence and patient number nearly doubled compared with the 2006 survey. Onset age is shifting toward elderly. Second, treatment strategy is making progress. Until the first decade of the 2000s, thymectomy and high-dose oral steroids were the mainstream to treat generalized MG. However, adverse effects and impaired quality of life due to steroid administration have become a problem. Japan MG Registry Study Group has been investigating this issue since 2009, and proposed early fast-acting treatment accompanied with low-dose prednisolone to secure patients' quality of life. This strategy is gradually being supported by neurologists in Japan. Third, several molecular targeted drugs have been available since 2017. Additionally, clinical trials of many other drugs are in progress. It is time to reconsider the treatment strategy for MG. Meanwhile, the revised Japanese guidelines for MG and Lambert–Eaton myasthenic syndrome was published in 2022. Three review articles that delineate clinical research on MG in Japan appear in this issue. Suzuki et al. summarized the data of over a period of 10 years from the Japan MG Registry Study. Four crosssectional surveys, as well as a longitudinal study, have been carried out in this period. The early fast-acting treatment strategy was derived from this study. This article introduces the data from the fourth largest multicenter survey in 2021, obtaining detailed clinical information from 1710 consecutive MG patients all over Japan. Yoshikawa described the epidemiological survey of MG in Japan, which he carried out in 2018. He also compared the data with previous surveys, and found (i) increasing prevalence; (ii) increasing lateand elderly-onset; (iii) decreasing female dominance; (iv) decreasing infantile-onset (onset age of 0–4 years); and (v) decreasing frequencies of crisis. Clinical features of MG are greatly changing over time. Murai et al. introduced newly published Japanese clinical guidelines for MG/Lambert–Eaton myasthenic syndrome. In these guidelines, diagnostic criteria of MG were revised, and six clinical subtypes were clarified. It was also mentioned that a high-dose oral steroid regimen with escalation and de-escalation schedule is not recommended. Refractory MG was defined, and a treatment algorithm was proposed. The guidelines are expected to serve to bridge the present with the molecular targeted treatment eras. As aforementioned, detailed clinical research on MG has been carried out for >10 years in Japan. Experiencing the recent significant change in the clinical scene of MG, continuing these studies will become more crucial.","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42383129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of sex hormones in neuroinflammation in Alzheimer's disease","authors":"Kasumi Maekawa,&nbsp;Koji Yamanaka","doi":"10.1111/cen3.12744","DOIUrl":"10.1111/cen3.12744","url":null,"abstract":"<p>Neuroinflammation, which is mediated by microglia, astrocytes, and infiltrated immune cells and leads to the subsequent production of proinflammatory molecules, is associated with the pathomechanism of Alzheimer's disease (AD). As the incidence of AD is higher in females than males, multiple studies have focused on the relationship between sex hormones and AD pathology. Androgen and estrogen receptors are expressed throughout the brain, including the hippocampus; thus, both sex hormones may regulate brain function, including cognitive function. Endogenous sex hormone levels are depleted by aging and cancer therapies, including prostate cancer and breast cancer therapies. Previous cohort studies have revealed that these conditions may also increase the risk of developing AD. Here we review previous findings from epidemiologic and preclinical studies on AD and provide an overview of the roles of sex hormones as risk factors of AD and regulators of AD pathology, including neuroinflammation. Furthermore, we discuss the therapeutic potential of sex hormone supplementation as a preventive or therapeutic treatment for AD based on the results of randomized control trials.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41277252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifactorial glial responses and their contributions to Alzheimer's disease continuum","authors":"Masanori Hijioka,&nbsp;Tatsuya Manabe,&nbsp;Takashi Saito","doi":"10.1111/cen3.12745","DOIUrl":"10.1111/cen3.12745","url":null,"abstract":"<p>Alzheimer's disease (AD) is the most common neurocognitive disorder. Various factors are intricately intertwined before clinical symptoms appear, although both amyloid-β peptide deposition and neurofibrillary tangle formation (i.e. pathological hallmarks of the AD brain) are established. Among such factors, glial responses have been increasingly recognized as important roles in the progression of these pathologies and viewed as one component of the AD continuum. However, the detailed molecular and cellular mechanisms of glial function underlying AD pathogenesis remain to be elucidated. Recent studies showed that peripheral immunity, gut microbiota or environmental factors influence brain pathophysiologies through communication with glial cells in the brain. This disease complexity makes understanding AD etiology difficult and hinders the development of effective therapeutic strategies to tackle this disease. Conversely, aged patients often suffer from multiple – not a single – diseases as multimorbidity, and AD pathogenesis might be related to pathologies caused by other diseases. Hence, investigating AD as a systemic disease has become critical for identifying therapeutic interventions. This review aimed to summarize current knowledge on AD research and share perspectives for understanding glial functions regarding AD pathophysiology.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41548013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of neuromuscular medullary thymic epithelial cells in thymoma with myasthenia gravis","authors":"Tatsusada Okuno,&nbsp;Yoshiaki Yasumizu,&nbsp;Hideki Mochizuki","doi":"10.1111/cen3.12743","DOIUrl":"https://doi.org/10.1111/cen3.12743","url":null,"abstract":"Autoimmune diseases lead to antibodies mistakenly recognizing and attacking host cells as foreign invaders. One such disease is myasthenia gravis (MG), where the antibodies target neuromuscular-associated proteins, including the acetylcholine receptor. MG commonly occurs in patients with thymoma; however, the reasons for this remain unclear. Recently, a bioinformatic approach was undertaken to examine the relationship between these two diseases.","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50125589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transverse myelitis following bivalent COVID-19 booster vaccine and quadrivalent seasonal influenza vaccine","authors":"Teresa L. Xiao,&nbsp;Alexandre Zaharia,&nbsp;Anas S. Al-Smadi,&nbsp;Caleb J. Murphy","doi":"10.1111/cen3.12742","DOIUrl":"10.1111/cen3.12742","url":null,"abstract":"<p>We present a case of acute partial transverse myelitis (TM) that developed 6 d following covaccination with a bivalent COVID-19 booster vaccine and quadrivalent influenza vaccine. Although initial imaging of the thoracic spine was nonspecific, repeat magnetic resonance imaging (MRI) showed a T2 hyperintense lesion with contrast enhancement, consistent with TM. The risk of rare but catastrophic neurologic complications following the bivalent COVID-19 booster vaccine and/or covaccination with COVID-19 and influenza vaccines is the subject of ongoing investigation in the medical community.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.12742","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48020342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Japanese clinical guidelines 2022 for myasthenia gravis and Lambert–Eaton myasthenic syndrome","authors":"Hiroyuki Murai,&nbsp;Kimiaki Utsugisawa,&nbsp;Masakatsu Motomura,&nbsp;Tomihiro Imai,&nbsp;Akiyuki Uzawa,&nbsp;Shigeaki Suzuki","doi":"10.1111/cen3.12739","DOIUrl":"10.1111/cen3.12739","url":null,"abstract":"<p>The revised Japanese clinical guidelines for myasthenia gravis (MG) and Lambert–Eaton myasthenic syndrome (LEMS) were published in 2022. The notable points in these guidelines (GLs) are as follows: (i) these are the first Japanese GLs to include a description of LEMS; (ii) diagnostic criteria of MG are revised to lessen the incidence of false negative patients; (iii) MG is divided into six clinical subtypes; (iv) a high-dose oral steroid regimen with escalation and de-escalation schedule is not recommended by the GLs; (v) the GLs promote the early fast-acting treatment strategy initially proposed in the previous GLs; (vi) refractory MG is defined; (vii) the use of molecular targeted drugs is included; (viii) diagnostic criteria of LEMS are proposed; and (ix) treatment algorithms for both MG and LEMS are presented. These new GLs are expected to improve the patients' quality of life and will serve to bridge the present era with the molecular targeted treatment eras.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.12739","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42857810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}