Clinical and Experimental Neuroimmunology最新文献

{"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":"14 1","pages":"4"},"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":"14 2","pages":"100-109"},"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":"14 2","pages":"82-91"},"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":"14 2","pages":"80-81"},"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":"14 3","pages":"138-141"},"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":"14 1","pages":"19-27"},"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}

{"title":"All differential diagnoses of cerebellar ataxia should be ruled out before SARS-CoV-2 is blamed as the cause","authors":"Josef Finsterer","doi":"10.1111/cen3.12737","DOIUrl":"10.1111/cen3.12737","url":null,"abstract":"We read","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"14 2","pages":"122"},"PeriodicalIF":0.0,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9877961/pdf/CEN3-9999-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10592109","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":"Epidemiological study of myasthenia gravis in Japan","authors":"Hiroaki Yoshikawa","doi":"10.1111/cen3.12736","DOIUrl":"10.1111/cen3.12736","url":null,"abstract":"<p>Myasthenia gravis (MG) is an autoimmune-mediated neurological disorder. The relationship between MG and thymic abnormalities is well recognized, and thymectomy is one of the therapies for anti-acetylcholine receptor antibody-positive MG. The major pathogenic factor is anti-acetylcholine receptor antibody followed by anti-muscle-specific kinase antibody, and commercial kits are available to detect these antibodies. Several decades ago, the prognosis of MG was not favorable; therefore, the Ministry of Health and Welfare (predecessor of the Ministry of Health, Labor and Welfare) organized a Taskforce for Intractable Diseases, which included MG, in 1972. The Taskforce carried out consecutive epidemiological studies for MG in 1973, 1987, 2006 and 2018. The four studies found: (i) increasing prevalence; (ii) increasing late- and elderly-onset; (iii) decreasing female dominancy; (iv) decreasing infantile-onset (onset age of 0–4 years); and (v) decreasing frequencies of crisis. The latest epidemiological study in Japan and studies from other countries suggest an increasing number of patients with anti-acetylcholine receptor antibody-positive MG without thymoma in the elderly. It is important to find out the causes of this phenomenon, which will improve the prevention of MG.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"14 1","pages":"13-18"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49494184","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":"Issue Information","authors":"","doi":"10.1111/odi.14414","DOIUrl":"https://doi.org/10.1111/odi.14414","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49037533","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":"Autoantibodies against contactin-associated protein 1 and complexes of paranode-specific proteins in chronic inflammatory demyelinating polyradiculoneuropathy","authors":"Michiaki Koga,&nbsp;Toshihiko Maeda,&nbsp;Fumitaka Shimizu,&nbsp;Takashi Kanda","doi":"10.1111/cen3.12735","DOIUrl":"10.1111/cen3.12735","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the frequency of serum autoantibodies targeting contactin-associated protein 1 (Caspr1) and its complexes with other paranode antigens, contactin-1 (CNTN1) and neurofascin 155 (NF155), in Japanese patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sera from 26 CIDP patients, 35 patients with Guillain–Barré syndrome, and 31 healthy individuals participated. Paranodal immunoglobulin G antibodies were quantified using enzyme-linked immunosorbent assays with commercially available recombinant proteins as antigens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Anti-Caspr1 antibodies were present in one participant (case 1, 3.8%) of CIDP, and negative in all Guillain–Barré syndrome patients and healthy participant. Case 1 was a man who developed subacute distal limb-predominant muscle weakness and sensory ataxia with postural hand tremor at 69 years-of-age, and therapeutic benefit of intravenous immunoglobulin and oral steroids was inadequate. The detected anti-Caspr1 antibodies predominantly belonged to the immunoglobulin G4 subclass, and the addition of CNTN1 to Caspr1 as an antigen increased antibody reactivity, although the increase was just 20–30% at most. The presence of autoantibodies against paranode protein complexes, including Caspr1/CNTN1, Caspr1/NF155 and Caspr1/CNTN1/NF155, was confirmed in several CIDP patients, although they also had anti-Caspr1 or anti-NF155 antibodies; thus, in our cohort, there were no patients with autoantibodies that specifically recognized paranode protein complexes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the first confirmed Japanese case of anti-Caspr1 antibody-positive CIDP with a clinical signature similar to that of patients of Western origin. Our preliminary study did not identify the presence of specific antibodies against the paranode protein complexes, and the primary target antigen is likely Caspr1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"14 2","pages":"116-121"},"PeriodicalIF":0.0,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45050723","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}