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 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.

Association between inflammatory bowel diseases and Parkinson's disease: systematic review and meta-analysis

Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease(IBD) and Parkinson's disease(PD). However, the epidemiological features of these two diseases are different. This review systematically evaluated the relationship between inflammatory bowel diseases and Parkinson's disease risk. We searched Pub Med, Embase, and Cochrane databases to retrieve observational studies of IBD and PD published from inception to October 2019. Nine observational studies, involving 12,177,520 patients, were included in the final analysis. None of the studies had Newcastle–Ottawa Scale scores that suggested a high risk of bias. After adjusting for confounders and excluding heterogeneous studies, the overall risk of PD was significantly higher in IBD patients than in the general population(adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15–1.34, P < 0.001). A metaanalysis of the temporal relationship revealed that the incidence of IBD was significantly increased before(adjusted hazard ratio [HR] = 1.26, 95% CI: 1.18–1.35, P < 0.001) and after(adjusted RR = 1.40, 95% CI: 1.20–1.80, P < 0.001) PD diagnosis. After excluding a heterogeneous study, the pooled risk of PD development in patients with ulcerative colitis(adjusted HR = 1.25, 95% CI: 1.13–1.38, P < 0.001) or Crohn's disease(adjusted HR = 1.33, 95% CI: 1.21–1.45, P < 0.01) was significantly increased. Subgroup analysis revealed no significant differences in risk between men(adjusted HR = 1.23, 95% CI: 1.10–1.39) and women(adjusted HR = 1.26, 95% CI: 1.10–1.43);however, older(> 65 years old) IBD patients(adjusted HR = 1.32, 95% CI: 1.17–1.48) may have a higher risk than younger(≤ 65 years old) patients(adjusted HR = 1.24, 95% CI: 1.08–1.42). Patients with IBD who were not treated with anti-tumor necrosis factor-α or azathioprine had significantly higher PD risk(adjusted HR = 1.6, 95% CI: 1.2–2.2). Thus, our meta-analysis indicates a certain correlation between IBD and PD, and suggests that IBD may moderately increase PD risk regardless of sex, especially in patients over 65 years of age. Moreover, early anti-inflammatory therapies for IBD might reduce the risk of developing PD. Our findings suggest an urgent need for an individualized screening strategy for patients with IBD. However, most studies included in this paper were observational, and more randomized controlled trials are needed to confirm the precise association between IBD and PD.

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.

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.

一站式护理服务模式在中枢神经系统特发性炎性脱髓鞘病患者中的应用效果

目的 探究入院-出院-随访一站式护理服务模式在中枢神经系统特发性炎性脱髓鞘病(central nervous system-idiopathic infl ammatory demyelinating diseases,CNS-IIDDs)患者中的应用效果。方法 选择2021年1月—2022年6月收治的60例CNS-IIDDs患者作为研究对象,按照组间基线资料均衡可比的原则分为对照组和观察组,各30例。对照组使用常规护理服务模式;观察组在对照组基础上实施入院-出院-随访一站式护理服务模式。采用疾病不确定感成人量表(Mishel Uncertainty in Illness Scale,MUIS-A)和疾病不确定感社区量表(Mishel Uncertainty in Illness Scale Community Form,MUIS-CF)评价两组患者疾病不确定感,采用Morisky服药依从性量表(Morisky Medication Adherence Scale,MMAS-8)评价患者的用药依从性,采用焦虑自评量表(Self-Rating Anxiety Scale,SAS)和抑郁自评量表(Self-Rating Depression Scale,SDS)评价患者的心理状态,采用简明健康调查量表(the Mos Item Short From Health Survey,SF-36)和满意度评价量表分别评价患者的生存质量及护理满意度。结果 干预后,观察组患者MUIS-A、MUIS-CF、SAS、SDS评分均低于对照组,差异均有统计学意义(P<0.05);观察组患者依从性高于对照组,生存质量各项维度评分和护理满意度总分均高于对照组,差异均有统计学意义(P<0.05)。结论 入院-出院-随访一站式护理服务模式可以降低CNS-IIDDs患者疾病不确定感,提升其用药依从性,有利于改善患者的心理状态和生存质量,有效提升患者护理满意度。

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.

Neurological complications of hematopoietic cell transplantation in children and adults

Hematopoietic cell transplantation（HCT） is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen（HLA）-matched donor（allogeneic） or from the patient（autologous）. Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease（Gv HD）. Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, Gv HD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT：（1） early complications（in the first month）-related to harvesting of stem cells, during conditioning（drug toxicity, posterior reversible encephalopathy syndrome）, related to pancytopenia,（2） intermediate phase complications（second to sixth month）-central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus,（3） late phase complications（after sixth month）-neurological complications of Gv HD, second neoplasms and relapses of the original disease.

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.

中枢神经系统瘤样脱髓鞘病变1例并文献复习

报道1例中枢神经系统瘤样脱髓鞘病变患者临床资料,并进行文献复习。

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.

肝移植术后脱髓鞘疾病病因的研究进展

肝移植术后发生神经系统的脱髓鞘疾病较为少见,但近年有上升的趋势。发病早期易被误诊为免疫抑制剂引起的精神症状,当其表现在中枢神经系统时危害较大,一旦发生将会严重影响肝移植术后患者的早期生存率和长期生活质量。而当其表现在周围神经系统时,多为隐匿起病,给早期诊断和治疗带来不便。因此,对于肝移植术后并发脱髓鞘疾病应以预防为主,了解各种脱髓鞘疾病的发病原因,有助于临床医生防患于未然。但肝移植术后并发脱髓鞘疾病的确切机制仍未明确。本文复习了相关报道,总结了肝移植术后常见脱髓鞘疾病可能的发生机制,为更好地预防和治疗肝移植术后并发脱髓鞘疾病提供参考。

儿童髓鞘少突胶质细胞糖蛋白抗体相关急性播散性脑脊髓炎的临床特点

目的探讨儿童髓鞘少突胶质细胞糖蛋白(MOG)抗体相关急性播散性脑脊髓炎(ADEM)的临床特点。方法回顾性分析2019年5月至2020年12月在泉州市儿童医院小儿神经内科住院的18例MOG抗体相关的ADEM患儿的临床表现、影像学检查、治疗及随访情况。结果MOG抗体相关ADEM患儿发病年龄为2.5~8岁,中位年龄4.6岁,其中5岁以下占66.7%;55%以上有前驱感染史或疫苗接种史,临床表现以脑病最多见(100%),其次为抽搐(44.4%);所有患儿头颅MRI均异常,大部分表现为皮质下白质、深部白质广泛、边界不清的大片状病灶;脊髓病变1例,表现为长节段脊髓炎;所有患儿急性期均予大剂量静脉甲泼尼龙(IVMP)冲击联合静脉丙种球蛋白(IVIG)治疗,病情均改善,约11.1%复发,缓解期使用小剂量激素维持配合每月IVIG未再复发。结论儿童MOG抗体相关ADEM以5岁以下多见,临床表现以脑病及抽搐最常见,急性期IVMP联合IVIG治疗反应好,部分可复发,缓解期小剂量激素维持配合每月IVIG可能可减少复发。

中枢神经系统炎性脱髓鞘疾病的临床研究

目的:分析中枢神经系统炎性脱髓鞘疾病的临床特点与激素治疗效果。方法:对2010年12月~2016年12月进入我院的中枢神经系统炎性脱髓鞘疾病患者90例进行临床回顾性分析,其中,多发性硬化30例为A组,视神经脊髓炎30例为B组,急性脊髓炎30例为C组。结果:三种不种疾病临床特征不同,特别是在急性起病和亚急性起病方面。结论:三种疾病作为三种不同的疾病实体,在临床表现、脑脊液(CSF)检查、诱发电位等方面均存在差异。

粒淋比在中枢神经系统特发性炎性脱髓鞘疾病中的临床意义

目的:探究外周血中性粒细胞淋巴细胞比值(粒淋比)在中枢神经系统特发性炎性脱髓鞘疾病(IIDDs)中的临床意义。方法:收集在武汉同济医院确诊的中枢神经系统IIDDs患者81例纳入病例组,包括视神经脊髓炎谱系疾病(NMOSD)23例,髓鞘少突胶质细胞糖蛋白抗体相关疾病(MOGAD)者19例,多发性硬化(MS)25例,自身免疫性胶质纤维酸性蛋白星形细胞病(A-GFAP-A)14例;并选择同时期入院的非自身免疫性神经系统疾病患者20例纳入对照组。收集2组患者的人口学数据及临床资料。采用扩展残疾状态量表(EDSS)评分评估疾病严重程度。检测血常规,比较外周血粒淋比在对照组及各病例组的区别及其与疾病严重程度的关系。结果:NMOSD及A-GFAP-A患者的粒淋比高于对照组,差异有统计学意义(P=0.0184,0.0014);MOGAD和MS患者的粒淋比与对照组差异无统计学意义(P=0.095,0.205)。各病例组患者的粒淋比与入院时EDSS评分之间均无显著相关性(P>0.05)。结论:粒淋比在NMOSD及A-GFAP-A中会升高,但无法预测疾病的严重程度。

MRI表现非典型的原发性中枢神经系统淋巴瘤三例

原发性中枢神经系统淋巴瘤(PCNSL)是少见的中枢神经系统肿瘤。少数PCNSL患者的临床症状及影像学表现与中枢神经系统炎症性脱髓鞘病变非常相似。该文报道MRI表现非典型的3例PCNSL患者,最初均被误诊为中枢神经系统炎症性脱髓鞘病变,首次经糖皮质激素治疗后病情均缓解,MRI显示病灶减少、缩小,但其后病情反复发作且加重,MRI显示病灶增多、增大,磁共振波谱均显示胆碱峰与氮-乙酰天门冬氨酸峰的比值大于2.0,最后均经脑病理活组织检查(活检)才确诊为PCNSL,化学治疗后病情均稳定。部分PCNSL患者因临床症状无特异性且MRI表现非典型,容易被误诊为炎症性脱髓鞘病变,延误了治疗,因此,临床上对于与该文报道的有相似表现的患者,应高度怀疑PCNSL,尽快行脑病理活检以助确诊,及时选择合适的治疗方案。

原发小脑伯基特淋巴瘤一例

患者男,29岁,发作性头晕伴复视4月余,加重1月余。1月前至当地医院就诊,查颅脑MRI考虑为特发性炎性脱髓鞘(idiopathic inflammatory demyelinating diseases,IIDD)并给予激素冲击治疗,症状缓解。而后复视症状加重,且逐渐出现头痛难忍,头痛剧烈时伴有恶心,出现嗜睡、精神差,双下肢肌力下降等症状。遂转至本院进一步治疗。

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。