Overview of emerging therapies for demyelinating diseases

This paper provides an overview of autoimmune disorders of the central nervous system,specifically those caused by demyelination.We explore new research regarding potential therapeutic interventions,particularly those aimed at inducing remyelination.Remyelination is a detailed process,involving many cell types–oligodendrocyte precursor cells(OPCs),astrocytes,and microglia–and both the innate and adaptive immune systems.Our discussion of this process includes the differentiation potential of neural stem cells,the function of adult OPCs,and the impact of molecular mediators on myelin repair.Emerging therapies are also explored,with mechanisms of action including the induction of OPC differentiation,the transplantation of mesenchymal stem cells,and the use of molecular mediators.Further,we discuss current medical advancements in relation to many myelin-related disorders,including multiple sclerosis,optic neuritis,neuromyelitis optica spectrum disorder,myelin oligodendrocyte glycoprotein antibodyassociated disease,transverse myelitis,and acute disseminated encephalomyelitis.Beyond these emerging systemic therapies,we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries.Despite these aforementioned scientific advancements,this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients’quality of life.

The Olig family affects central nervous system development and disease

Neural cell differentiation and maturation is a critical step during central nervous system devel-opment. The oligodendrocyte transcription family （Olig family） is known to be an important factor in regulating neural cell differentiation. Because of this, the Olig family also affects acute and chronic central nervous system diseases, including brain injury, multiple sclerosis, and even gliomas. Improved understanding about the functions of the Olig family in central nervous system development and disease will greatly aid novel breakthroughs in central nervous system diseases. This review investigates the role of the Olig family in central nervous system develop- ment and related diseases.

Idiopathic inflammatory demyelinating diseases of the central nervous system in patients following allogeneic hematopoietic stem cell transplantation： a retrospective analysis of incidence, risk factors and survival

Background AIIogeneic hematopoietic stem cell transplantation （allo-HSCT） is a curative therapy for many hematological diseases, but there are many complications following alIo-HSCT, among which neurological complications （NC） are one of the most commonly described ones. However, little is known about idiopathic inflammatory demyelinating diseases （IIDDs） of the central nervous system （CNS） in patients following alIo-HSCT. Methods A nested case-control study was conducted in a large cohort of 1365 patients, who underwent alIo-HSCT at the Institute of Hematology and Peking University People＇s Hospital, between January 2004 and December 2009, 36 patients of whom developed CNS IIDDs. Kaplan-Meier method, univariate and multivariate Cox regression were applied in our statistical analysis using SPSS 16.0. Results The cumulative incidence of all cases of IIDDs at 6 years posttransplantation was 3.6%. Thirty-five patients （97.2%） suffered IIDDs after transplantation, 16 patients （44.4%） between day 0 to day 100 post-transplantation, 10 patients （27.8%） between day 100 to 1 year post-transplantation, and 9 patients （25.0%） 1 year post-transplantation. Multivariate regression analysis identified donor type （P=0.031）, infection （P=0.009）, and acute lymphatic leukemia （P=0.017） as independent risk factors for posttransplantation IIDDs. The median survival time of patients with IIDDs was 514 days after transplantation （95% CI： 223-805）. Survival at 6 years was significantly lower in patients who developed the diseases compared to those who did not （26.6% vs. 73.5%, P 〈0.001）. Of the 36 patients experiencing IIDDs, 58.3% （n=21） died. The causes of death were graft-versus-host disease （GVHD） （n=4）, underlying disease relapse （n=3）, infections （n=12）, and other causes （n=2）. Conclusions IIDDs is an uncommon but serious complication of alIo-HSCT, especially in patients with a primary diagnosis of acute lymphatic leukemia, mismatched transplants, and infections. Our study results indicate that patients with IIDDs tend toward a poor prognosis following alIo-HSCT.

The clinical features and potential mechanisms of cognitive disorders in peripheral autoimmune and inflammatory diseases

According to a study from World Health Organization’s Global Burden of Disease,mental and neurological disorders have accounted for 13%of global diseases in recent years and are on the rise.Neuropsychiatric conditions or neuroinflammatory disorders are linked by the presence of an exaggerated immune response both peripherally and in the central nervous system(CNS).Cognitive dysfunction(CD)encompasses a complex group of diseases and has frequently been described in the field of autoimmune diseases,especially in multiple non-CNS-related autoimmune diseases.Recent studies have provided various hypotheses regarding the occurrence of cognitive impairment in autoimmune diseases,including that abnormally activated immune cells can disrupt the integrity of the blood-brain barrier(BBB)to trigger a central neuroinflammatory response.When the BBB is intact,autoantibodies and pro-inflammatory molecules in peripheral circulation can enter the brain to activate microglia,inducing CNS inflammation and CD.However,the mechanisms explaining the association between the immune system and neural function and their contribution to diseases are uncertain.In this review,we used clinical statistics to illustrate the correlation between CD and autoimmune diseases that do not directly affect the CNS,summarized the clinical features and mechanisms by which autoimmune diseases trigger cognitive impairment,and explored existing knowledge regarding the link between CD and autoimmune diseases from the perspective of the field of neuroimmunology.

Contributions of neurotropic human herpesviruses herpes simplex virus 1 and human herpesvirus 6 to neurodegenerative disease pathology

Human herpesviruses （HVs） have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system （CNS）. The ability of HVs to enter a state of latency, a defining char- acteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease （NDD） patholo- gy by highlighting two prominent members of the HV family, herpes simplex virus 1 （HSV-1） and human herpesvirus 6 （HHV-6）. We （i） introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then （ii） review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer＇s disease （AD） and multiple sclerosis （MS）, respectively. We then （iii） highlight and dis- cuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we （iv） discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs.

Neuroimaging of corpus callosum in central nervous system demyelinating disorders

Corpus callosum (CC) is the largest white matter structure in the brain, consisting of 200-250 million contralateral axonal projections. It is the major commissural pathway connecting the hemispheres of human brain. The pathology of CC includes wide variety of entities that arise from different causes such as congenital, inflammatory, tumoral, degenerative, infectious, etc. This study reviews the most reliable neuroimaging data of human CC in central nervous system (CNS) demyelinating diseases to facilitate the understanding of different pathological entities of the CC and their role in anticipation of probable prognostic findings. After a brief description of normal anatomy and functions of CC, this review examines the most valuable findings obtained using conventional and functional magnetic resonance imaging. It also demonstrates the most well organized findings of how CC features influence prognostic factors of demyelinating disorders, which could have a great value for choosing proper therapy methods. The authors also provided a brief review of other demyelinating disorders which are primarily caused by other pathological factors other than autoimmunity. As a conclusion, the authors showed the importance of CC as an critical part of the brain, which should be explored by different methods of imaging, correspondent to clinical evaluation of CNS demyelinating disorder to widen our knowledge on pathology and clinical patterns of such disorders.

Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma （PCNSL） is an aggressive non-Hodgkin Lymphoma, most frequently diffuse large B-cell lymphoma in immunocompetent patients, which is confined to the central nervous system. In the past two decades, its incidence has been steadily increasing.

中枢神经系统脱髓鞘疾病PET示踪剂研究进展

目前临床缺乏监测中枢神经系统脱髓鞘疾病髓鞘脱失和再生的影像学手段。现有的各种MRI技术均以间接方式检测髓鞘脱失情况,易受其他干扰因素的影响。PET作为一种可在分子水平对神经系统疾病进行成像的技术,可以实现功能、代谢、生化的实时成像,弥补MRI的局限性。近年来,髓鞘PET显像示踪剂发展迅速,目前以髓鞘为靶点的示踪剂主要包括刚果红衍生物、二苯乙烯衍生物、硫磺素衍生物。新型多模态医学影像学技术PET/MRI结合PET分子水平成像和MRI软组织分辨率高的优势,实现解剖结构、功能、代谢、生化影像的实时融合,未来可能成为监测中枢神经系统脱髓鞘疾病的有效手段。

Should mast cells be considered therapeutic targets in multiple sclerosis?

Mast cells are immune cells of the myeloid lineage that are found throughout the body,including the central nervous system.They perform many functions associated with innate and specific immunity,angiogenesis,and vascular homeostasis.Moreover,they have been implicated in a series of pathologies(e.g.,hypersensitivity reactions,tumors,and inflammatory disorders).In this review,we propose that this cell could be a relevant therapeutic target in multiple sclerosis,which is a central nervous system degenerative disease.To support this proposition,we describe the general biological properties of mast cells,their contribution to innate and specific immunity,and the participation of mast cells in the various stages of multiple sclerosis and experimental autoimmune encephalomyelitis development.The final part of this review is dedicated to an overview of the available mast cells immunomodulatory drugs and their activity on multiple sclerosis and experimental autoimmune encephalomyelitis,including our own experience related to the effect of ketotifen fumarate on experimental autoimmune encephalomyelitis evolution.

同心圆硬化1例病例报告并文献复习

目的进一步提高罕见病症——同心圆硬化诊断的准确性,使更多患者得到有效治疗。方法报道1例同心圆硬化的临床特点、脑脊液检查、头颅磁共振(MR)表现。系统检索文献并复习已报道的病例,总结同心圆硬化的发病机制、临床特点、脑脊液表现、头颅磁共振特征、治疗及预后。结果从中国生物医学文献数据库及PubMed数据库中检索到已确诊同心圆硬化84例,结合本病例分析发现:同心圆硬化发病机制可能与病毒感染引起的自身免疫反应相关;临床表现无特异性,以肢体偏瘫、偏身麻木、言语障碍、颅神经麻痹等症状多见;少部分患者脑脊液检查寡克隆带阳性;头颅MRI扫描可见类似于洋葱头样、树木年轮样黑白相间的类圆形病灶,增强扫描可见斑片状及边缘花环样强化。磁共振波谱学(MRS)检查显示:病灶区域NAA峰降低,Cho峰升高,Lip峰出现。早期大剂量皮质类固醇激素治疗有效,预后良好,致残率/致死率低。结论头颅MRI特征性改变对同心圆硬化具有较大诊断价值,早期大剂量皮质类固醇激素治疗效果较好。

儿童抗髓鞘少突胶质细胞糖蛋白IgG相关疾病的MRI征象分析

目的探讨儿童抗髓鞘少突胶质细胞糖蛋白IgG相关疾病(MOGAD)的MRI特征。方法病例系列报告。纳入2018年1月—2021年12月聊城市人民医院确诊MOGAD的10例患儿, 其中男6例、女4例, 年龄2~9(5.9±2.4)岁。10例患儿治疗前行颅脑MR常规扫描, 9例行全脊柱MR常规扫描, 4例行眼眶MR常规扫描。观察指标:(1)记录MRI对MOGAD颅脑、脊髓和视神经病变的检出情况;(2)总结颅脑MOGAD病变分布位置、形态及信号特点;(3)观察脊髓MOGAD病变部位、脊髓有无肿胀, 统计长节段脊髓MOGAD病变的患儿数量;(4)观察视神经病变部位、视神经有无肿胀;(5)将患儿末次随访时复查MRI与治疗前进行对比, 观察病变转归情况。结果治疗前MRI显示:(1)颅脑病变10例, 脊髓病变5例, 视神经病变2例。(2)10例MOGAD颅脑病变均为多发, 9例双侧、1例单侧。4例仅累及幕上, 1例仅累及幕下, 5例同时累及幕上和幕下。幕上病变位于皮层下白质7例, 脑室周围白质7例, 丘脑5例, 基底节区4例, 胼胝体2例, 单侧皮质1例;幕下病变位于桥脑6例, 同时累及小脑4例、中脑2例。病变均为非对称性。MOGAD病变形态均表现为无定形斑片状、斑点状, 其中2例同时出现斑块样改变;2例病变DWI序列显示弥散受限。(3)MOGAD脊髓病变5例, 均为单发、累及胸段脊髓的长节段脊髓病变, 其中4例同时累及颈段脊髓, 未发现腰段脊髓受累;2例出现脊髓肿胀。(4)MOGAD视神经病变2例, 均为双侧, 其中1例视神经全程受累、1例视神经前部受累, 视交叉及视束均无受累。2例视神经均无肿胀。(5)10例患儿经治疗后均好转出院, 出院后随访8~29(12.9±5.8)个月。随访期间患儿定期复查MRI, 均未见复发。末次随访MRI显示, 2例患儿颅脑病变完全消失, 1例脊髓病变完全消失, 其余7例患儿颅脑、脊髓或视神经MOGAD病变范围均减小或病灶数均减少。结论儿童MOGAD中, 颅脑病变最常见, 其次为脊髓和视神经;不同部位的MOGAD MRI表现具有一定特征性, 认识这些影像学特征, 可以提高临床医生诊断儿童MOGAD的准确率, 为早期治疗提供重要参考。

瘤样炎性脱髓鞘病与脑胶质瘤及中枢神经系统淋巴瘤患者头颅CT的对比研究

目的探讨头颅CT对于瘤样炎性脱髓鞘病（TIDD）与脑胶质瘤及原发性中枢神经系统淋巴瘤（PCNSL）的鉴别意义。方法对20例TIDD患者[男性10例，女性10例；发病年龄6～51岁，平均年龄（35．6＋14．0）岁]与32例脑胶质瘤[男性16例，女性16例；发病年龄12～75岁，平均年龄（42．0＋19．8）岁]及6例PCNSL[男性3例，女性3例；发病年龄32—68岁，平均年龄（53．8±11．8）岁]的头颅CT特点进行对比分析。结果（1）38例脑肿瘤患者中19例（50．0％）头颅CT显示病灶呈高密度（其中胶质瘤14例，PCNSL5例），10例（26．3％）呈等密度（其中胶质瘤9例，PCNSL1例），9例（23．7％）呈低密度（均为胶质瘤）；而TIDD组病灶均为低密度。（2）所有PCNSL及90％高级别胶质瘤（胶质瘤WHO分级Ⅲ、Ⅳ级）均有头颅CT病灶呈高或等密度特点，而Ⅱ级者仅占41．7％。（3）19例头颅CT显示高密度病灶的脑肿瘤患者中，7例呈不均匀点片状高密度影（其中胶质瘤6例，PCNSL1例），呈均匀大片状高密度影（其中胶质瘤1例，PCNSL3例）、周边高密度环（均为胶质瘤）及弥漫性高密度影（其中胶质瘤3例，PCNSL1例）者各4例。另外，脑肿瘤组仅4例PCNSL行增强CT检查，均有增强（平扫高密度者3例，等密度1例），而TIDD组7例行增强CT仅3例可见轻度强化。（4）经Spearman’s rho相关分析发现，胶质瘤组头颅CT病灶呈高或等密度与WHO分级密切相关（r=0．435，P=0．013），即胶质瘤WHO分级Ⅲ、Ⅳ级患者和PCNSL患者头颅CT病灶呈高或等密度的出现概率较高，而胶质瘤WHO分级Ⅱ级者则较少出现。结论头颅CT对脑胶质瘤及PCNSL与TIDD的诊断及鉴别意义显著，该检查简单、经济、实用，是对于头颅MRI、磁共振波谱等影像技术的必要补充，若CT显示占位病变为高密度和（或）显著强化，可基本除外TIDD。

Wiskott-Aldrich综合征合并中枢神经系统脱髓鞘病变一例并文献复习

目的 通过报道1例典型Wiskott-Aldrich综合征（WAS）患儿临床特点结合文献复习,探讨该病与中枢神经系统自身免疫性疾病的相关性及可能的发病机制.方法 报道1例WAS合并神经系统脱髓鞘病变患儿.分析患儿的临床特征、实验室检查（包括血常规、免疫功能等）以及影像学特点,并提取患儿外周血中DNA行基因检测,同时复习相关文献.结果 该患儿具有湿疹、血小板减少及免疫缺陷等典型WAS特征,并伴有中枢神经系统脱髓鞘病变.其基因检测结果为C400G＞C p.（ALa134Pro）.ALa134Pro突变,为错义突变,翻译蛋白中第134位氨基酸残基由丙氨酸变为脯氨酸.该患儿合并有中枢神经系统脱髓鞘病变,引发我们关注其发病机制,国内尚无WAS合并中枢神经系统脱髓鞘病变的报道和研究,参阅国外研究结果,其发病可能由其突变基因引起.结论 WAS患儿合并中枢神经系统脱髓鞘病变可能由其突变基因导致WAS蛋白表达障碍,进一步引起非红系造血细胞对外界刺激反应时的信号传导和细胞骨架组合障碍,造成淋巴细胞迁移、信号传导及免疫突触形成异常.

中枢神经系统自身免疫性脱髓鞘病患者门诊随访依从性调查

目的研究中枢神经系统自身免疫性脱髓鞘病患者门诊随访依从性及其影响因素,为提出针对性措施提供依据。方法拟定调查问卷,采用电话问询的方式对中枢神经系统脱髓鞘疾病数据库中的患者进行问卷调查,将所研究的影响因素进行分析。结果单因素分析表明,男性、对疾病特点缺乏了解、初中及以下教育程度、非城镇医疗保险、外省居住和症状最重时扩展致残状态量表(EDSS)评分较低的患者门诊随诊依从性较差。多因素logistic回归分析结果显示,对疾病特点是否了解、是否外省居住和症状最重时EDSS评分具有统计学意义(P<0.05)。其中对疾病特点是否了解(OR=4.327,95%CI=2.200～8.511)和是否外省居住(OR=4.377,95%CI=1.133～16.907)是影响患者能否定期门诊随诊的独立危险因素;而症状最重时EDSS评分则为患者能否定期门诊随诊的保护因素(OR=0.845,95%CI=0.724～0.986),症状最重时EDSS评分越高的患者门诊随诊依从性更好。对目前治疗无信心是患者门诊随诊依从性差常见的主观原因。结论对疾病特点缺乏了解、症状最重时EDSS评分较低和居住在外省的患者门诊随诊依从性更差。

自身免疫性脑炎与中枢神经系统特发性炎性脱髓鞘病重叠

自身免疫性脑炎是自身免疫机制导致的脑部炎性疾病,其相关抗体可分为细胞内靶向抗原抗体和细胞表面靶向抗原抗体2类。中枢神经系统特发性炎性脱髓鞘病(central nervous system idiopathic inflammatory demyelinating diseases,CNS-IIDDs)是一组免疫相关的特发于脑(包括视神经)和(或)脊髓的炎性脱髓鞘疾病,其与数种自身抗体(包括抗水通道蛋白4抗体、抗髓鞘少突胶质细胞糖蛋白抗体等)相关。临床上,自身免疫性脑炎可与CNS-IIDDs重叠。本文结合相关文献对自身免疫性脑炎和CNS-IIDDs以及2者重叠的疾病特征进行总结,以期为临床医师提供相关诊治建议。如要明确2者重叠的临床特征和发病机制,还需开展更多高质量的研究。