Most disease-modifying treatments (DMTs) for patients with multiple sclerosis (PwMS) do not influence the risk and outcome of coronavirus disease (COVID-19), except for anti-CD20 monoclonal antibodies (ocrelizumab and rituximab). However, data on Japanese PwMS are lacking. Thus, we evaluated the risk of COVID-19 in Japanese PwMS undergoing DMTs.
Methods
In this retrospective cross-sectional study, we used the Japanese administrative database. The incidence of COVID-19 between January 1, 2022, and December 31, 2024 was compared between PwMS who were administered different DMTs.
Results
In total, 61 of 1044 (5.8%) PwMS who were administered baseline treatments and 102 of 1253 (8.1%) PwMS who were administered high-efficacy treatments had COVID-19. The prevalence of COVID-19 was significantly higher in PwMS receiving high-efficacy treatments than in those receiving baseline treatments. However, this prevalence did not differ significantly among PwMS on different individual DMTs.
Conclusion
Although high-efficacy therapy may increase the overall prevalence of COVID-19, no specific DMT approved in Japan was associated with an increased prevalence of COVID-19 among Japanese PwMS.
{"title":"Effect of Disease-Modifying Treatments in Japanese Patients With Multiple Sclerosis During the Coronavirus Disease 2019 Pandemic","authors":"Taisuke Ogawa, Juichi Fujimori, Daisuke Kikuchi, Ichiro Nakashima","doi":"10.1111/cen3.70008","DOIUrl":"https://doi.org/10.1111/cen3.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Most disease-modifying treatments (DMTs) for patients with multiple sclerosis (PwMS) do not influence the risk and outcome of coronavirus disease (COVID-19), except for anti-CD20 monoclonal antibodies (ocrelizumab and rituximab). However, data on Japanese PwMS are lacking. Thus, we evaluated the risk of COVID-19 in Japanese PwMS undergoing DMTs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective cross-sectional study, we used the Japanese administrative database. The incidence of COVID-19 between January 1, 2022, and December 31, 2024 was compared between PwMS who were administered different DMTs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 61 of 1044 (5.8%) PwMS who were administered baseline treatments and 102 of 1253 (8.1%) PwMS who were administered high-efficacy treatments had COVID-19. The prevalence of COVID-19 was significantly higher in PwMS receiving high-efficacy treatments than in those receiving baseline treatments. However, this prevalence did not differ significantly among PwMS on different individual DMTs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although high-efficacy therapy may increase the overall prevalence of COVID-19, no specific DMT approved in Japan was associated with an increased prevalence of COVID-19 among Japanese PwMS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751289","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}
The mechanisms underlying therapeutic hypothermia, which protects neurons after severe brain damage, are not completely understood. Based on a previous study, hypothermia reduced the release of tumor necrosis factor (TNF)-α and interleukin (IL)-17. Meanwhile, hyperthermia promoted the release of TNF-α and IL-17. Leukocyte transmigration via the endothelium is mediated by endothelial cell junctional molecules, such as junctional adhesion molecule (JAM)-A and vascular endothelial cadherin (VE-cadherin), positively and negatively, respectively. In the ischemic brain, the diapedesis of leukocytes into the tissues results in enhanced postischemic brain inflammation and intensified brain injury. The current study aimed to evaluate the mechanisms underlying this treatment by assessing the effects of TNF-α and IL-17 on brain microvascular endothelial cell (BMVEC) junctional molecule and the effects of hypothermia and hyperthermia on its expression.
Methods
The expression of JAM-A and VE-cadherin, which are BMVEC junctional molecules, was measured at the protein level via immunocytochemistry.
Results
TNF-α and IL-17 increased the expression of JAM-A in BMVECs in a concentration-dependent manner. Compared with normothermia, hypothermia did not affect the expression of JAM-A and VE-cadherin in BMVECs stimulated with TNF-α or IL-17. Meanwhile, hyperthermia reduced the basal expression of VE-cadherin in BMVECs, with this expression being further reduced by stimulation with IL-17.
Conclusions
The hypothermic suppression of TNF-α and IL-17 release may decrease JAM-A expression in BMVECs. Meanwhile, hyperthermia itself may decrease VE-cadherin expression in BMVECs. The former may contribute to suppressing, while the latter may promote, leukocyte extravasation.
{"title":"Concentration-Dependent Increase in the Expression of Junctional Adhesion Molecule-A in Brain Microvascular Endothelial Cells in Response to Proinflammatory Cytokines and Hyperthermic Decrease in the Expression of Vascular Endothelial Cadherin in These Cells","authors":"Tomohiro Matsui, Yuji Mochiduki","doi":"10.1111/cen3.70006","DOIUrl":"https://doi.org/10.1111/cen3.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The mechanisms underlying therapeutic hypothermia, which protects neurons after severe brain damage, are not completely understood. Based on a previous study, hypothermia reduced the release of tumor necrosis factor (TNF)-α and interleukin (IL)-17. Meanwhile, hyperthermia promoted the release of TNF-α and IL-17. Leukocyte transmigration via the endothelium is mediated by endothelial cell junctional molecules, such as junctional adhesion molecule (JAM)-A and vascular endothelial cadherin (VE-cadherin), positively and negatively, respectively. In the ischemic brain, the diapedesis of leukocytes into the tissues results in enhanced postischemic brain inflammation and intensified brain injury. The current study aimed to evaluate the mechanisms underlying this treatment by assessing the effects of TNF-α and IL-17 on brain microvascular endothelial cell (BMVEC) junctional molecule and the effects of hypothermia and hyperthermia on its expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression of JAM-A and VE-cadherin, which are BMVEC junctional molecules, was measured at the protein level via immunocytochemistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TNF-α and IL-17 increased the expression of JAM-A in BMVECs in a concentration-dependent manner. Compared with normothermia, hypothermia did not affect the expression of JAM-A and VE-cadherin in BMVECs stimulated with TNF-α or IL-17. Meanwhile, hyperthermia reduced the basal expression of VE-cadherin in BMVECs, with this expression being further reduced by stimulation with IL-17.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The hypothermic suppression of TNF-α and IL-17 release may decrease JAM-A expression in BMVECs. Meanwhile, hyperthermia itself may decrease VE-cadherin expression in BMVECs. The former may contribute to suppressing, while the latter may promote, leukocyte extravasation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751290","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}
Autoimmune cerebellar ataxia (ACA) is a condition in which the cerebellum is the primary location of inflammation due to autoimmune encephalitis caused by neuroimmune conditions. Although ACA is rare, it remains an important differential diagnosis, distinct from other neurodegenerative conditions, such as multiple system atrophy. An accurate diagnosis requires the integration of clinical history, blood tests, cerebrospinal fluid analysis, magnetic resonance imaging and malignancy screening. Over 30 neural antibodies associated with ACA have been reported as diagnostic biomarkers. The clinical profile of frequently reported antibodies, such as anti-Yo and anti-GAD, are well-defined, although that of rarer antibodies remain unclear. Cell-based assays are the standard method for detecting most neural antibodies, but testing for a wide range of antibodies is costly. Immunoblots assays and tissue-based assays are useful for screening. Further investigations into clinical profiles and advancements in screening methods are required to identify neural antibodies. ACA should not be overlooked, due to its treatable nature. Acute phase treatments, such as intravenous methylprednisolone and immunoglobulin, plasma exchange, and rituximab, are effective. Maintenance therapy using steroids and/or immunosuppressants is used to prevent relapse and progression. However, maintenance therapy requires individualized decisions due to limited clinical evidence. Additionally, treatment responses might vary depending on the type of neural antibody. In the future, the development of biomarkers and improved autoantibody testing methods is important to develop novel therapies and optimal immunotherapy for patients with ACA.
{"title":"Autoimmune cerebellar ataxia: An overlooked, but treatable, neuroimmune condition","authors":"Hiroaki Yaguchi, Akihiko Kudo, Ichiro Yabe","doi":"10.1111/cen3.70004","DOIUrl":"https://doi.org/10.1111/cen3.70004","url":null,"abstract":"<p>Autoimmune cerebellar ataxia (ACA) is a condition in which the cerebellum is the primary location of inflammation due to autoimmune encephalitis caused by neuroimmune conditions. Although ACA is rare, it remains an important differential diagnosis, distinct from other neurodegenerative conditions, such as multiple system atrophy. An accurate diagnosis requires the integration of clinical history, blood tests, cerebrospinal fluid analysis, magnetic resonance imaging and malignancy screening. Over 30 neural antibodies associated with ACA have been reported as diagnostic biomarkers. The clinical profile of frequently reported antibodies, such as anti-Yo and anti-GAD, are well-defined, although that of rarer antibodies remain unclear. Cell-based assays are the standard method for detecting most neural antibodies, but testing for a wide range of antibodies is costly. Immunoblots assays and tissue-based assays are useful for screening. Further investigations into clinical profiles and advancements in screening methods are required to identify neural antibodies. ACA should not be overlooked, due to its treatable nature. Acute phase treatments, such as intravenous methylprednisolone and immunoglobulin, plasma exchange, and rituximab, are effective. Maintenance therapy using steroids and/or immunosuppressants is used to prevent relapse and progression. However, maintenance therapy requires individualized decisions due to limited clinical evidence. Additionally, treatment responses might vary depending on the type of neural antibody. In the future, the development of biomarkers and improved autoantibody testing methods is important to develop novel therapies and optimal immunotherapy for patients with ACA.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 2","pages":"161-173"},"PeriodicalIF":0.0,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919543","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}
Various combinations of antibodies to glycolipids or ganglioside complexes (GSCs) are found in Guillain–Barré syndrome (GBS) and Miller Fisher syndrome (MFS). Specific combinations of co-occurring antibodies are thought to be associated with specific clinical phenotypes of GBS/MFS. However, the clinical implications of antibody combinations have not been fully investigated. This study was performed to identify probable antibody combinations and to examine correlations between these combinations and clinical symptoms.
Methods
The subjects were 315 patients with GBS (n = 226) or MFS (n = 89) with anti-glycolipid-antibodies. The co-occurrence of anti-glycolipid antibodies was analyzed using ‘KH Coder,’ a software program for identifying co-occurrence networks. Correlations between subgroups of co-occurring antibodies and clinical features were also analyzed.
Results
Five unique autoantibody subgroups were identified. In each subgroup, the main autoantibodies were Anti-GQ1b, −GT1a antibodies (subgroup 1), Anti-GM1, −GA1, -GalNAc-GD1a, and -GD1b antibodies (subgroup 2), Anti-GM1/GM2, −GM1/GalNAc-GD1a, and other Anti-GSC antibodies (subgroup 3), Anti-GM1/GT1b, −GM1/GalNAc-GD1a, and other Anti-GSC antibodies (subgroup 4), and Anti-GD1a/GQ1b, -GD1a/GT1a, and other Anti-GSC antibodies (subgroup 5). Antecedent infection (P = .0376), clinical diagnosis (P < .0001), clinical phenotype (P < .0001) and cranial nerve involvement (P < .001) differed significantly across subgroups. Subgroup 1 most frequently had respiratory antecedent infection, contained MFS cases, and had cases that developed cranial nerve deficiencies. Subgroup 3 contained the largest proportion of GBS cases.
Conclusion
These results suggest that co-occurrence of anti-glycolipid antibodies can be classified into five subgroups. Each subgroup exhibits different clinical characteristics.
{"title":"Co-occurrence analysis of the correlation of antibodies to glycolipids or ganglioside complexes with clinical features: A retrospective cohort study","authors":"Yu Hongo, Kenichi Kaida, Yukari Komuta, Hiroshi Takazaki, Keishi Yamazaki, Taro Matsui, Keiko Miyake, Kazushi Suzuki","doi":"10.1111/cen3.70005","DOIUrl":"https://doi.org/10.1111/cen3.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Various combinations of antibodies to glycolipids or ganglioside complexes (GSCs) are found in Guillain–Barré syndrome (GBS) and Miller Fisher syndrome (MFS). Specific combinations of co-occurring antibodies are thought to be associated with specific clinical phenotypes of GBS/MFS. However, the clinical implications of antibody combinations have not been fully investigated. This study was performed to identify probable antibody combinations and to examine correlations between these combinations and clinical symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The subjects were 315 patients with GBS (<i>n</i> = 226) or MFS (<i>n</i> = 89) with anti-glycolipid-antibodies. The co-occurrence of anti-glycolipid antibodies was analyzed using ‘KH Coder,’ a software program for identifying co-occurrence networks. Correlations between subgroups of co-occurring antibodies and clinical features were also analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five unique autoantibody subgroups were identified. In each subgroup, the main autoantibodies were Anti-GQ1b, −GT1a antibodies (subgroup 1), Anti-GM1, −GA1, -GalNAc-GD1a, and -GD1b antibodies (subgroup 2), Anti-GM1/GM2, −GM1/GalNAc-GD1a, and other Anti-GSC antibodies (subgroup 3), Anti-GM1/GT1b, −GM1/GalNAc-GD1a, and other Anti-GSC antibodies (subgroup 4), and Anti-GD1a/GQ1b, -GD1a/GT1a, and other Anti-GSC antibodies (subgroup 5). Antecedent infection (<i>P =</i> .0376), clinical diagnosis (<i>P <</i> .0001), clinical phenotype (<i>P <</i> .0001) and cranial nerve involvement (<i>P <</i> .001) differed significantly across subgroups. Subgroup 1 most frequently had respiratory antecedent infection, contained MFS cases, and had cases that developed cranial nerve deficiencies. Subgroup 3 contained the largest proportion of GBS cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results suggest that co-occurrence of anti-glycolipid antibodies can be classified into five subgroups. Each subgroup exhibits different clinical characteristics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751209","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}
Fingolimod is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML).
Case Presentation
We report a 63-year-old woman with severe clinical decline (Expanded Disability Status Scale increasing from 3.5 to 7.0). She started fingolimod 0.5 mg/day at the age of 51 years in the FTY720 trial in Japan, and has been taking it orally ever since. Brain magnetic resonance imaging showed abnormal signals from the subcortical region to the deep white matter, mainly in the right frontal lobe. No gadolinium-enhancing lesions were observed, and diffusion-weighted imaging showed marginal hyperintense and central hypointense signals; the characteristic findings in PML. We found her cerebrospinal fluid was positive for John Cunningham polyomavirus DNA, and the diagnosis of PML was made. We administered several steroid pulses in case of immune reconstitution inflammatory syndrome. The progression of symptoms and the enlargement of magnetic resonance imaging lesions stopped after 3 months.
Conclusions
This case shows that PML should always be kept in mind as a side-effect of disease-modifying therapy for multiple sclerosis.
{"title":"Case of fingolimod-associated progressive multifocal leukoencephalopathy in multiple sclerosis","authors":"Hiroki Maesaka, Hirohumi Konishi, Shunya Nakane, Yuji Nakatsuji","doi":"10.1111/cen3.12823","DOIUrl":"https://doi.org/10.1111/cen3.12823","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fingolimod is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>We report a 63-year-old woman with severe clinical decline (Expanded Disability Status Scale increasing from 3.5 to 7.0). She started fingolimod 0.5 mg/day at the age of 51 years in the FTY720 trial in Japan, and has been taking it orally ever since. Brain magnetic resonance imaging showed abnormal signals from the subcortical region to the deep white matter, mainly in the right frontal lobe. No gadolinium-enhancing lesions were observed, and diffusion-weighted imaging showed marginal hyperintense and central hypointense signals; the characteristic findings in PML. We found her cerebrospinal fluid was positive for John Cunningham polyomavirus DNA, and the diagnosis of PML was made. We administered several steroid pulses in case of immune reconstitution inflammatory syndrome. The progression of symptoms and the enlargement of magnetic resonance imaging lesions stopped after 3 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This case shows that PML should always be kept in mind as a side-effect of disease-modifying therapy for multiple sclerosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"357-360"},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436086","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}
Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the central nervous system (CNS), particularly affecting the spinal cord, and is caused by HTLV-1 infection. The biased geographic distribution of HTLV-1-infected individuals facilitated the early identification of a causal relationship between HTLV-1 infection and related diseases soon after the discovery of the virus. In contrast, such a relationship would have been challenging to establish without this geographic clustering. Similarly, Epstein–Barr virus (EBV), which infects ~95% of the global population, has recently been implicated in the pathogenesis of multiple sclerosis (MS), another chronic inflammatory CNS disease. Advances in seroepidemiology, immunology, genomics, and biomarker research in large MS cohorts have shed light on EBV's critical role in disease development. These insights provide a framework for understanding the molecular mechanisms underlying both MS and HAM/TSP, which remain incompletely elucidated. In this review, we compare HTLV-1 with EBV, focusing on their shared strategies for establishing long-term latency in the host and their roles in CNS inflammation. By analyzing the relationship between HAM/TSP and MS through virological and molecular biological perspectives, we propose that both conditions may represent chronic inflammatory diseases of the CNS triggered by viral infections. This hypothesis offers a novel perspective on the pathogenesis of these diseases. Finally, we discuss current challenges and future directions in the treatment and prevention of HAM/TSP and MS.
{"title":"Human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis and multiple sclerosis: Viral strategies and their implications","authors":"Makoto Nakashima, Yoshihisa Yamano","doi":"10.1111/cen3.70001","DOIUrl":"https://doi.org/10.1111/cen3.70001","url":null,"abstract":"<p>Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the central nervous system (CNS), particularly affecting the spinal cord, and is caused by HTLV-1 infection. The biased geographic distribution of HTLV-1-infected individuals facilitated the early identification of a causal relationship between HTLV-1 infection and related diseases soon after the discovery of the virus. In contrast, such a relationship would have been challenging to establish without this geographic clustering. Similarly, Epstein–Barr virus (EBV), which infects ~95% of the global population, has recently been implicated in the pathogenesis of multiple sclerosis (MS), another chronic inflammatory CNS disease. Advances in seroepidemiology, immunology, genomics, and biomarker research in large MS cohorts have shed light on EBV's critical role in disease development. These insights provide a framework for understanding the molecular mechanisms underlying both MS and HAM/TSP, which remain incompletely elucidated. In this review, we compare HTLV-1 with EBV, focusing on their shared strategies for establishing long-term latency in the host and their roles in CNS inflammation. By analyzing the relationship between HAM/TSP and MS through virological and molecular biological perspectives, we propose that both conditions may represent chronic inflammatory diseases of the CNS triggered by viral infections. This hypothesis offers a novel perspective on the pathogenesis of these diseases. Finally, we discuss current challenges and future directions in the treatment and prevention of HAM/TSP and MS.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 2","pages":"149-160"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919604","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}
There are no effective therapies for nonmotor symptoms of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), including cognitive impairment, fatigue, depression, and pain. Transcranial direct current stimulation (tDCS), a neuromodulatory technique, enhances rehabilitation effects, and has been applied to multiple neurological diseases. We attempted to clarify the effectiveness of tDCS on the nonmotor symptoms of MS/NMOSD.
Methods
A double-blind, randomized cros-over trial was conducted with five MS/NMOSD patients randomly assigned to active (real) or sham tDCS groups. Patients received 10 sessions of tDCS combined with rehabilitation, with assessments at baseline and poststimulation, A second session under the alternate condition followed. The anodal electrode was placed over M1 (C3 in the 10–20 system), and the cathode over Fp2, delivering 1.0 mA for 900 s. Functional magnetic resonance imaging was conducted before and after stimulation to assess functional connectivity (FC) using region of interest (ROI)-to-ROI analysis across six ROIs.
Results
No adverse events related to tDCS were observed. A significant improvement was observed in working memory and information-processing ability, as assessed by using the Paced Auditory Serial Addition 2-s version after active stimulation compared to sham stimulation. In the anterior cingulate cortex-precuneus FC, significant changes were observed following active stimulation.
Conclusion
Anodal tDCS over M1 may be a useful means of improving cognitive function in patients with MS/NMOSD and altered FCs beyond M1.
{"title":"Effects of transcranial direct current stimulation on multiple sclerosis and neuromyelitis optica spectrum disorder: A double-blind, randomized, crossover trial","authors":"Ryoko Shibuya, Koji Ishikuro, Noriaki Hattori, Shuhei Takasawa, Hiroaki Hirosawa, Mamoru Yamamoto, Hirofumi Konishi, Shunya Nakane, Kyo Noguchi, Yuji Nakatsuji","doi":"10.1111/cen3.70002","DOIUrl":"https://doi.org/10.1111/cen3.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>There are no effective therapies for nonmotor symptoms of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), including cognitive impairment, fatigue, depression, and pain. Transcranial direct current stimulation (tDCS), a neuromodulatory technique, enhances rehabilitation effects, and has been applied to multiple neurological diseases. We attempted to clarify the effectiveness of tDCS on the nonmotor symptoms of MS/NMOSD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A double-blind, randomized cros-over trial was conducted with five MS/NMOSD patients randomly assigned to active (real) or sham tDCS groups. Patients received 10 sessions of tDCS combined with rehabilitation, with assessments at baseline and poststimulation, A second session under the alternate condition followed. The anodal electrode was placed over M1 (C3 in the 10–20 system), and the cathode over Fp2, delivering 1.0 mA for 900 s. Functional magnetic resonance imaging was conducted before and after stimulation to assess functional connectivity (FC) using region of interest (ROI)-to-ROI analysis across six ROIs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No adverse events related to tDCS were observed. A significant improvement was observed in working memory and information-processing ability, as assessed by using the Paced Auditory Serial Addition 2-s version after active stimulation compared to sham stimulation. In the anterior cingulate cortex-precuneus FC, significant changes were observed following active stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Anodal tDCS over M1 may be a useful means of improving cognitive function in patients with MS/NMOSD and altered FCs beyond M1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"348-356"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436414","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/cen3.12832","DOIUrl":"https://doi.org/10.1111/cen3.12832","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 1","pages":"84"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455668","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}
Recently, the EUROIMMUN anti-acetylcholine receptor antibody (AChR Ab) enzyme-linked immunosorbent assay (ELISA) became commercially available in Japan, but its clinical performance has not been comprehensively researched. This is the first diagnostic evaluation of the AChR Ab ELISA carried out in the Japanese population, including stratification of myasthenia gravis (MG) patients according to the length of treatment.
Methods
Concentrations of AChR Ab in sera from clinically confirmed MG patients (n = 85) and non-MG control participants (n = 52) were measured and compared between ELISA and radioimmunoassay (RIA). Sensitivity and concordance of the assays were further analyzed in a stratified manner according to the treatment period. AChR Ab concentration was monitored over the treatment periods (0–5 months, n = 7).
Results
The concordance rate between ELISA and RIA was 87% (ĸ = 0.74). Specificity of ELISA and RIA were 96% and 100%, respectively. Sensitivity was lower in ELISA (62%) compared with RIA (76%). Subgroup analysis showed that the sensitivity of both assays was identical (90%) in the treatment-naïve and short-term medicated patients (≤3 years), but decreased in patients undergoing mid- and late-stage treatment. The concentration of AChR Ab showed reducing trends over the treatment period in both ELISA and RIA (r = 0.915).
Conclusions
In addition to other considerable benefits of ELISA, such as automation and avoidance of radioisotope waste, its high overall concordance and equal sensitivity with RIA, especially in treatment-naïve and early-stage treatment patients, suggest that the ELISA can be a valuable option supporting MG diagnostics in Japan.
{"title":"Comparison of the sensitivity of anti-acetylcholine receptor enzyme-linked immunosorbent assay and radioimmunoassay in different treatment periods","authors":"Naoki Kawaguchi, Asami Imafuku, Satoshi Fujii, Fumiko Tsuno, Shinya Yamada, Etsuko Kuwabara, Sandra Saschenbrecker","doi":"10.1111/cen3.12833","DOIUrl":"https://doi.org/10.1111/cen3.12833","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Recently, the EUROIMMUN anti-acetylcholine receptor antibody (AChR Ab) enzyme-linked immunosorbent assay (ELISA) became commercially available in Japan, but its clinical performance has not been comprehensively researched. This is the first diagnostic evaluation of the AChR Ab ELISA carried out in the Japanese population, including stratification of myasthenia gravis (MG) patients according to the length of treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Concentrations of AChR Ab in sera from clinically confirmed MG patients (<i>n</i> = 85) and non-MG control participants (<i>n</i> = 52) were measured and compared between ELISA and radioimmunoassay (RIA). Sensitivity and concordance of the assays were further analyzed in a stratified manner according to the treatment period. AChR Ab concentration was monitored over the treatment periods (0–5 months, <i>n</i> = 7).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The concordance rate between ELISA and RIA was 87% (ĸ = 0.74). Specificity of ELISA and RIA were 96% and 100%, respectively. Sensitivity was lower in ELISA (62%) compared with RIA (76%). Subgroup analysis showed that the sensitivity of both assays was identical (90%) in the treatment-naïve and short-term medicated patients (≤3 years), but decreased in patients undergoing mid- and late-stage treatment. The concentration of AChR Ab showed reducing trends over the treatment period in both ELISA and RIA (<i>r</i> = 0.915).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In addition to other considerable benefits of ELISA, such as automation and avoidance of radioisotope waste, its high overall concordance and equal sensitivity with RIA, especially in treatment-naïve and early-stage treatment patients, suggest that the ELISA can be a valuable option supporting MG diagnostics in Japan.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"361-369"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145435984","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}
Hadar Gilad, Josepha Horowitz, Sivan Bloch, Daniel Golan
Objectives
It is known that the benefit of intravenous methylprednisolone (IVMP) in multiple sclerosis-related optic neuritis (MS-ON) is limited to an accelerated recovery. We aimed to evaluate the impact of time from symptoms onset to IVMP initiation and of IVMP dose on visual recovery among people with MS-ON.
Methods
A retrospective cohort study of MS-ON was undertaken. The associations between time from symptoms onset to IVMP as well as dose of IVMP and best-corrected visual acuity (BCVA) improvement after 6–12 mo were analyzed.
Results
Sixty-one events of ON from 61 patients were included (Age: 32 ± 13, Female: 46 [75%]). ON was the initial presentation of MS for 45 (74%) participants. The mean time from symptoms onset to initiation of IVMP was 5.8 ± 4.6 d. Twenty-eight episodes (46%) were treated with 3 g and 33 episodes (54%) were treated with 4.5 g IVMP. The proportion of events with complete recovery of BCVA was similar between those who were treated up to 3 d, 4 to 7 or ≥8 d from onset (46%, 74%, 58%, respectively (χ2(2) = 3.9, P = .14). Complete recovery of visual acuity was achieved in 71% and 49% of events treated with 3 and 4.5 g IVMP, respectively (χ2(1) = 3.3, P = .07). On multivariate analysis, only nadir visual acuity predicted incomplete recovery of BCVA (odds ratio [OR] = 2.02; P = .05); IVMP timing and dose did not.
Conclusion
While intravenous corticosteroids remain the mainstay of treatment, increasing the dose or starting treatment earlier does not seem to improve long-term recovery from MS-ON. A substantial proportion of people with MS-ON remain with residual impairment of BCVA, highlighting the need for better treatments.
目的：众所周知，静脉注射甲基强的松龙（IVMP）治疗多发性硬化症相关视神经炎（MS-ON）的益处仅限于加速恢复。我们的目的是评估从症状出现到IVMP启动的时间和IVMP剂量对MS-ON患者视力恢复的影响。方法对MS-ON进行回顾性队列研究。分析从症状出现到IVMP的时间以及IVMP剂量与6-12个月后最佳矫正视力（BCVA）改善之间的关系。结果共纳入61例ON患者61例（年龄：32±13岁，女性：46例[75%]）。45名（74%）参与者最初表现为多发性硬化症。从症状出现到IVMP启动的平均时间为5.8±4.6 d。28例（46%）用3g治疗，33例（54%）用4.5 g IVMP治疗。在发病后治疗3 d、4 ~ 7 d或≥8 d的患者中，BCVA完全恢复的事件比例相似（分别为46%、74%、58%）（χ2(2) = 3.9, P = 0.14）。使用3 g和4.5 g IVMP治疗的患者视力完全恢复的比例分别为71%和49% （χ2(1) = 3.3, P = 0.07）。在多因素分析中，只有最低视力能预测BCVA不完全恢复（优势比[OR] = 2.02; P = 0.05）；IVMP的时间和剂量没有变化。结论静脉注射糖皮质激素仍然是治疗的主要手段，但增加剂量或早期开始治疗似乎并不能改善MS-ON的长期康复。相当大比例的MS-ON患者仍然存在BCVA残留损伤，这突出了更好治疗的必要性。
{"title":"Effect of time to initiation and dose of methylprednisolone on outcome in multiple sclerosis-related optic neuritis","authors":"Hadar Gilad, Josepha Horowitz, Sivan Bloch, Daniel Golan","doi":"10.1111/cen3.70000","DOIUrl":"https://doi.org/10.1111/cen3.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>It is known that the benefit of intravenous methylprednisolone (IVMP) in multiple sclerosis-related optic neuritis (MS-ON) is limited to an accelerated recovery. We aimed to evaluate the impact of time from symptoms onset to IVMP initiation and of IVMP dose on visual recovery among people with MS-ON.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cohort study of MS-ON was undertaken. The associations between time from symptoms onset to IVMP as well as dose of IVMP and best-corrected visual acuity (BCVA) improvement after 6–12 mo were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixty-one events of ON from 61 patients were included (Age: 32 ± 13, Female: 46 [75%]). ON was the initial presentation of MS for 45 (74%) participants. The mean time from symptoms onset to initiation of IVMP was 5.8 ± 4.6 d. Twenty-eight episodes (46%) were treated with 3 g and 33 episodes (54%) were treated with 4.5 g IVMP. The proportion of events with complete recovery of BCVA was similar between those who were treated up to 3 d, 4 to 7 or ≥8 d from onset (46%, 74%, 58%, respectively (<i>χ</i><sup>2</sup>(2) = 3.9, <i>P =</i> .14). Complete recovery of visual acuity was achieved in 71% and 49% of events treated with 3 and 4.5 g IVMP, respectively (<i>χ</i><sup>2</sup>(1) = 3.3, <i>P =</i> .07). On multivariate analysis, only nadir visual acuity predicted incomplete recovery of BCVA (odds ratio [OR] = 2.02; <i>P =</i> .05); IVMP timing and dose did not.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While intravenous corticosteroids remain the mainstay of treatment, increasing the dose or starting treatment earlier does not seem to improve long-term recovery from MS-ON. A substantial proportion of people with MS-ON remain with residual impairment of BCVA, highlighting the need for better treatments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"341-347"},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436193","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}
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