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 complic...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.展开更多
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
BACKGROUND Acute hemorrhagic leukoencephalitis(AHLE),also known as Weston-Hurst syndrome,is a very rare and fulminant form of demyelinating disorder.It is considered a hyperacute and severe variant of acute disseminat...BACKGROUND Acute hemorrhagic leukoencephalitis(AHLE),also known as Weston-Hurst syndrome,is a very rare and fulminant form of demyelinating disorder.It is considered a hyperacute and severe variant of acute disseminated encephalomyelitis.Clinically,patients present with fever,headache,seizures,and altered sensorium,which can rapidly progress to coma or death.Magnetic resonance imaging(MRI)is the investigation of choice and plays a pivotal role in diagnosing AHLE.The purpose of this article is to make readers familiar with the typical MRI features of AHLE and to discuss differentials.CASE SUMMARY This case series reports the clinical presentation and typical neuroimaging findings in four patients diagnosed with AHLE.All patients presented with acute neurological symptoms,such as severe headaches,seizures,and altered consciousness,often following a history of fever suggesting an infectious etiology.Additionally,laboratory investigations demonstrated elevated levels of serum inflammatory markers and neutrophilic pleocytosis on cerebrospinal fluid analysis,supporting a post-infectious etiology.MRI findings consistently revealed characteristic white matter lesions with hemorrhagic foci and vasogenic edema,indicative of widespread demyelination characteristic of AHLE.The outcomes varied,with two patients surviving but experiencing neurological sequelae,while two others unfortunately succumbed to the disease.The clinical data,laboratory results,and imaging findings from this case series were systematically compared with those from previously published studies.The key similarities and differences in clinical presentation,imaging characteristics,and outcomes are presented in a tabulated format.CONCLUSION AHLE is associated with high morbidity and mortality rates,emphasizing the need for early recognition,prompt intervention,and multidisciplinary management.Further research is needed to explain the pathophysiological mechanisms underlying AHLE,identify potential biomarkers for early diagnosis,and develop targeted therapies to improve patient outcomes.展开更多
Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas...Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas. It is often misdiagnosed as intramedullary tumor and surgically resected. In view of this, the clinical and magnetic resonance imaging manifestations and the pathological fea- tures of 36 cases of inflammatory demyelinating pseudotumer in the spinal cord were retrospec- tively analyzed and summarized. Most of these cases suffered from acute or subacute onset and exhibited a sensofimotor disorder. Among them, six cases were misdiagnosed as having intrame- dullary gliomas, and inflammatory demyelinating pseudotumor was only identified and pathologically confirmed after surgical resection. Lesions in the cervical and thoracic spinal cord were common. Magnetic resonance imaging revealed edema and space-occupying lesions to varying degrees at the cervical-thoracic junction, with a predominant feature of non-closed rosette-like reinforcement （open-loop sign）. Pathological examination showed perivascular cuffing of predominantly dense lymphocytes, and demyelination was observed in six of the misdiagnosed cases. These re- sults suggest that tumor-like inflammatory demyelinating disease in the spinal cord is a kind of special demyelinating disease that can be categorized as inflammatory pseudotumor. These solitary lesions are easily confused with intramedullary neoplasms. Patchy or non-closed reinforcement （open-ring sign） on magnetic resonance imaging is the predominant property of inflammatory de- myelinating pseudotumor, and inflammatory cell infiltration and demyelination are additional patho- logical properties.展开更多
Inflammatory bowel disease(IBD) is often associated with extraintestinal manifestations(EIMs) such as optic neuritis(ON),although this has been described in only a few adult patients so far,all of whom were affected w...Inflammatory bowel disease(IBD) is often associated with extraintestinal manifestations(EIMs) such as optic neuritis(ON),although this has been described in only a few adult patients so far,all of whom were affected with Crohn's disease(CD).Furthermore,ON and demyelinating diseases have been demonstrated to be more frequent in IBD patients than in control populations.In our current case report,we describe a child with active CD who developed sudden blindness due to bilateral ON that was not related to any known cause,and that promptly responded to a high dose of steroids.Investigations and a clinical follow-up have so far ruled out the development of demyelinating diseases in this patient.To our knowledge,this is the first report of ON in a pediatric patient with CD.Possible explanations for this case include an episodic EIM of an active bowel disease,an associated autoimmune disorder such as a recurrent isolated ON,the first manifestation of multiple sclerosis,or another demyelinating disease that could appear in a later follow-up.展开更多
Oligodendrocyte lineage cells(OL-lineage cells)are a cell population that are crucial for mammalian central nervous system(CNS)myelination.OL-lineage cells go through developmental stages,initially differentiating int...Oligodendrocyte lineage cells(OL-lineage cells)are a cell population that are crucial for mammalian central nervous system(CNS)myelination.OL-lineage cells go through developmental stages,initially differentiating into oligodendrocyte precursor cells(OPCs),before becoming immature oligodendrocytes,then mature oligodendrocytes(OLs).While the main function of cell lineage is in myelin formation,and increasing number of studies have turned to explore the immunological characteristics of these cells.Initially,these studies focused on discovering how OPCs and OLs are affected by the immune system,and then,how these immunological changes influence the myelination process.However,recent studies have uncovered another feature of OL-lineage cells in our immune systems.It would appear that OL-lineage cells also express immunological factors such as cytokines and chemokines in response to immune activation,and the expression of these factors changes under various pathologic conditions.Evidence suggests that OL-lineage cells actually modulate immune functions.Indeed,OL-lineage cells appear to play both"victim"and"agent"in the CNS which raises a number of questions.Here,we summarize immunologic changes in OL-lineage cells and their effects,as well as consider OL-lineage cell changes which influence immune cells under pathological conditions.We also describe some of the underlying mechanisms of these changes and their effects.Finally,we describe several studies which use OL-lineage cells as immunotherapeutic targets for demyelination diseases.展开更多
This study tested an improved fiber tracking algorithm, which was based on fiber assignment using a continuous tracking algorithm and a two-tensor model. Different models and tracking decisions were used by judging th...This study tested an improved fiber tracking algorithm, which was based on fiber assignment using a continuous tracking algorithm and a two-tensor model. Different models and tracking decisions were used by judging the type of estimation of each voxel. Thismethod should solve the cross-track problem. This study included eight healthy subjects, two axonal injury patients and seven demyelinating disease patients. This new algorithm clearly exhibited a difference in nerve fiber direction between axonal injury and demyelinating disease patients and healthy control subjects. Compared with fiber assignment with a continuous tracking algorithm, our novel method can track more and longer nerve fibers, and also can solve the fiber crossing problem.展开更多
Susac Syndrome (SS) is an autoimmune disease characterized by the clinical triad of encephalopathy, hearing loss and retinal arterial occlusions, with prevalent structural changes identified on brain magnetic resonanc...Susac Syndrome (SS) is an autoimmune disease characterized by the clinical triad of encephalopathy, hearing loss and retinal arterial occlusions, with prevalent structural changes identified on brain magnetic resonance imaging (white matter, corpus callosum, basal ganglia region and the thalamic region extending to the midbrain) in the majority of cases, which lead to cognitive manifestations of which there is a paucity of descriptions in the literature. The objective of this case study is to compare to post-rehabilitation neurocognitive profile of a 29-year-old woman with SS presenting with compromised intellectual and motor skills and cognitive functions, together with neuropsychiatric symptoms. Better performance was found in the neuropsychological assessment, with changes in the structural cerebral network evidenced on Diffusion Tensor Imaging (DTI) performed following the therapeutic and pharmacological intervention.展开更多
Charcot-Marie-Tooth disease type 1A（CMT1A） is caused by duplication of the peripheral myelin protein 22（PMP22） gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes melli...Charcot-Marie-Tooth disease type 1A（CMT1A） is caused by duplication of the peripheral myelin protein 22（PMP22） gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1 A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1 A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1 A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases.展开更多
Multiple sclerosis(MS)is an immune-mediated disease in the central nervous system thatis characterized by demyelination,axonal degeneration,and progressive neurological disability and is so far incurable.Current medic...Multiple sclerosis(MS)is an immune-mediated disease in the central nervous system thatis characterized by demyelination,axonal degeneration,and progressive neurological disability and is so far incurable.Current medications are predominantly immunetargeted but fail to prevent disease progression due to their inability to actively promote remyelination.Small molecules have been reported to promote myelin regeneration but their therapeutic efficacy is limited by insufficient immune modulation.Thus,the strategies achieving both immunomodulation and active myelin regeneration are highly desired.Here,we investigated a combination therapy(CT)for MS designed to simultaneously modulate immune responses and promote oligodendrocyte precursor cell differentiation and in situ remyelination in an experimental autoimmune encephalomyelitis mouse model.Remarkably,CT suppressed acute inflammatory activity,activated the signaling pathways for myelin development,induced the expression of myelin-related genes,and significantly promoted remyelination and the recovery of motor performance.Furthermore,a reduced immunomodulator dosage or shorter treatment duration with small-molecule drugs achieved comparable symptom reversal.Our findings demonstrate the potential of CT to address complex pathobiology and lay a foundation for developing novel therapeutic strategies for MS.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
Background： Neuromyelitis optica spectrum disorder （NMOSD） was long believed to be an aggressive form of multiple sclerosis （MS）. This study aimed to describe the clinical features of patients with MS and NMOSD t...Background： Neuromyelitis optica spectrum disorder （NMOSD） was long believed to be an aggressive form of multiple sclerosis （MS）. This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice. Methods： Data including the patients＇ serum and cerebrospinal fluid （CSF） tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein （MOG） autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody （AQP4-Ab）. The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was peribrmed to analyze the continuous variables. Results： Totally 85 MS patients （49%） and 90 NMOSD patients （51%） were enrolled, including 124 （71%） women and 51 （29%） men. Fewer MS patients （6%） had autoinamune diseases compared to NMOSD （19%） （x2= 6.9, P 〈 0.01 ）. Patients with NMOSD had higher Expanded Disability Status Scale scores （3.5 [3]） than MS group （2 [2]） （x2= -3.69, P 〈 0.01）. The CSF levels of white cell count and protein in both two groups were slightly elevated titan the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients （MS： 0, NMOSD： 67%; x2= 63.9, P 〈 0.01 ）. Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS （MS： 59%, NMOSD： 20%; x2= 25.7, P 〈 0.01）. No significant difference of MOG autoantibodies was found between the two groups. Conclusion： The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.展开更多
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 t...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.展开更多
Background The incentives and the factors that affect the onset and outcome of optic neuritis （ON） are not very clear. The aim of this study is to define and get a comprehensive understanding of the clinical profile...Background The incentives and the factors that affect the onset and outcome of optic neuritis （ON） are not very clear. The aim of this study is to define and get a comprehensive understanding of the clinical profile of ON, and to identify the factors that were related to the prognosis of the patients. Methods Medical records of patients with diagnosis of ON at Huashan Hospital, Fudan University between March 2008 and June 2011 were reviewed. Clinical features, ophthalmologic and neurologic assessments, neuroimaging studies, laboratory examinations, visual recovery, and final outcome of the patients were evaluated by the authors. Results Records of 50 patients （32 females and 18 males）, aged 15-56 years, were reviewed, in which 22% patients had a previous onset of ON. Maximal visual deficit was severe in 72.5% （〈20/200）. Abnormal rates of hormone levels and rheumatoid indicators were found in 54.2% and 25.0%. ANA test returned positive in 40%, oligoclonal banding （OCB） was identified in 31.3%, and Serum neuromyelitis optica （NMO）-IgG studies were abnormal in 25% of the patients. Neuroimaging abnormalities associated with ON were documented in six patients. Three of the 50 patients have been diagnosed with multiple sclerosis, and two with NMO. Visual acuity was 20/20 or better in 26.1% and 20/100 or worse in 39.1% affected eyes at the last visit. Poor visual acuity at onset is the main factor that would affect the final outcome of vision （P 〈0.05）. Conclusions Vision defects of this group of patients were severe. Females had a higher incidence of ON than males. Hormone levels, rheumatoid indicators and immune parameters may be related to the onset of ON. The severe reduction of visual acuity at onset may be related to the poor outcome of vision in ON patients.展开更多
基金This work was supported by grants From the National Natural Science Foundation of China （No. 81070449）, the National Science Foundation of Beijing （No. 7112139）, the National Key Technology Support Program （No. 2012BA138B03）, and the Capital Clinical Characteristic Application Foundation （No. Zl11107058811024）.The authors thank the nursing staff for providing excellent care to the alIo-HSCT recipients.
文摘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.
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
文摘BACKGROUND Acute hemorrhagic leukoencephalitis(AHLE),also known as Weston-Hurst syndrome,is a very rare and fulminant form of demyelinating disorder.It is considered a hyperacute and severe variant of acute disseminated encephalomyelitis.Clinically,patients present with fever,headache,seizures,and altered sensorium,which can rapidly progress to coma or death.Magnetic resonance imaging(MRI)is the investigation of choice and plays a pivotal role in diagnosing AHLE.The purpose of this article is to make readers familiar with the typical MRI features of AHLE and to discuss differentials.CASE SUMMARY This case series reports the clinical presentation and typical neuroimaging findings in four patients diagnosed with AHLE.All patients presented with acute neurological symptoms,such as severe headaches,seizures,and altered consciousness,often following a history of fever suggesting an infectious etiology.Additionally,laboratory investigations demonstrated elevated levels of serum inflammatory markers and neutrophilic pleocytosis on cerebrospinal fluid analysis,supporting a post-infectious etiology.MRI findings consistently revealed characteristic white matter lesions with hemorrhagic foci and vasogenic edema,indicative of widespread demyelination characteristic of AHLE.The outcomes varied,with two patients surviving but experiencing neurological sequelae,while two others unfortunately succumbed to the disease.The clinical data,laboratory results,and imaging findings from this case series were systematically compared with those from previously published studies.The key similarities and differences in clinical presentation,imaging characteristics,and outcomes are presented in a tabulated format.CONCLUSION AHLE is associated with high morbidity and mortality rates,emphasizing the need for early recognition,prompt intervention,and multidisciplinary management.Further research is needed to explain the pathophysiological mechanisms underlying AHLE,identify potential biomarkers for early diagnosis,and develop targeted therapies to improve patient outcomes.
文摘Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas. It is often misdiagnosed as intramedullary tumor and surgically resected. In view of this, the clinical and magnetic resonance imaging manifestations and the pathological fea- tures of 36 cases of inflammatory demyelinating pseudotumer in the spinal cord were retrospec- tively analyzed and summarized. Most of these cases suffered from acute or subacute onset and exhibited a sensofimotor disorder. Among them, six cases were misdiagnosed as having intrame- dullary gliomas, and inflammatory demyelinating pseudotumor was only identified and pathologically confirmed after surgical resection. Lesions in the cervical and thoracic spinal cord were common. Magnetic resonance imaging revealed edema and space-occupying lesions to varying degrees at the cervical-thoracic junction, with a predominant feature of non-closed rosette-like reinforcement （open-loop sign）. Pathological examination showed perivascular cuffing of predominantly dense lymphocytes, and demyelination was observed in six of the misdiagnosed cases. These re- sults suggest that tumor-like inflammatory demyelinating disease in the spinal cord is a kind of special demyelinating disease that can be categorized as inflammatory pseudotumor. These solitary lesions are easily confused with intramedullary neoplasms. Patchy or non-closed reinforcement （open-ring sign） on magnetic resonance imaging is the predominant property of inflammatory de- myelinating pseudotumor, and inflammatory cell infiltration and demyelination are additional patho- logical properties.
文摘Inflammatory bowel disease(IBD) is often associated with extraintestinal manifestations(EIMs) such as optic neuritis(ON),although this has been described in only a few adult patients so far,all of whom were affected with Crohn's disease(CD).Furthermore,ON and demyelinating diseases have been demonstrated to be more frequent in IBD patients than in control populations.In our current case report,we describe a child with active CD who developed sudden blindness due to bilateral ON that was not related to any known cause,and that promptly responded to a high dose of steroids.Investigations and a clinical follow-up have so far ruled out the development of demyelinating diseases in this patient.To our knowledge,this is the first report of ON in a pediatric patient with CD.Possible explanations for this case include an episodic EIM of an active bowel disease,an associated autoimmune disorder such as a recurrent isolated ON,the first manifestation of multiple sclerosis,or another demyelinating disease that could appear in a later follow-up.
基金This work was supported by research grants from Shenzhen Fundamental Research Program(Grants No.RCYX20200714114644167,JCYJ20190809161405495,and JCYJ20210324123212035)National Natural Science Foundation of China(Grants No.81971309,32170980,and 32070964)Guangdong Basic and Applied Basic Research Foundation(Grants No.2019A1515011333 and 2022B1515020012).
文摘Oligodendrocyte lineage cells(OL-lineage cells)are a cell population that are crucial for mammalian central nervous system(CNS)myelination.OL-lineage cells go through developmental stages,initially differentiating into oligodendrocyte precursor cells(OPCs),before becoming immature oligodendrocytes,then mature oligodendrocytes(OLs).While the main function of cell lineage is in myelin formation,and increasing number of studies have turned to explore the immunological characteristics of these cells.Initially,these studies focused on discovering how OPCs and OLs are affected by the immune system,and then,how these immunological changes influence the myelination process.However,recent studies have uncovered another feature of OL-lineage cells in our immune systems.It would appear that OL-lineage cells also express immunological factors such as cytokines and chemokines in response to immune activation,and the expression of these factors changes under various pathologic conditions.Evidence suggests that OL-lineage cells actually modulate immune functions.Indeed,OL-lineage cells appear to play both"victim"and"agent"in the CNS which raises a number of questions.Here,we summarize immunologic changes in OL-lineage cells and their effects,as well as consider OL-lineage cell changes which influence immune cells under pathological conditions.We also describe some of the underlying mechanisms of these changes and their effects.Finally,we describe several studies which use OL-lineage cells as immunotherapeutic targets for demyelination diseases.
基金supported by Xiamen Technology Projects Grand (The study of chronic cerebrovascular insufficiently in Magnetic Resonance Imaging), No.3502Z20084028
文摘This study tested an improved fiber tracking algorithm, which was based on fiber assignment using a continuous tracking algorithm and a two-tensor model. Different models and tracking decisions were used by judging the type of estimation of each voxel. Thismethod should solve the cross-track problem. This study included eight healthy subjects, two axonal injury patients and seven demyelinating disease patients. This new algorithm clearly exhibited a difference in nerve fiber direction between axonal injury and demyelinating disease patients and healthy control subjects. Compared with fiber assignment with a continuous tracking algorithm, our novel method can track more and longer nerve fibers, and also can solve the fiber crossing problem.
文摘Susac Syndrome (SS) is an autoimmune disease characterized by the clinical triad of encephalopathy, hearing loss and retinal arterial occlusions, with prevalent structural changes identified on brain magnetic resonance imaging (white matter, corpus callosum, basal ganglia region and the thalamic region extending to the midbrain) in the majority of cases, which lead to cognitive manifestations of which there is a paucity of descriptions in the literature. The objective of this case study is to compare to post-rehabilitation neurocognitive profile of a 29-year-old woman with SS presenting with compromised intellectual and motor skills and cognitive functions, together with neuropsychiatric symptoms. Better performance was found in the neuropsychological assessment, with changes in the structural cerebral network evidenced on Diffusion Tensor Imaging (DTI) performed following the therapeutic and pharmacological intervention.
文摘Charcot-Marie-Tooth disease type 1A（CMT1A） is caused by duplication of the peripheral myelin protein 22（PMP22） gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1 A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1 A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1 A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases.
基金supported by grants from the National Key R&D Program of China(2021YFA1100800)the National Natural Science Foundation of China(32370853).
文摘Multiple sclerosis(MS)is an immune-mediated disease in the central nervous system thatis characterized by demyelination,axonal degeneration,and progressive neurological disability and is so far incurable.Current medications are predominantly immunetargeted but fail to prevent disease progression due to their inability to actively promote remyelination.Small molecules have been reported to promote myelin regeneration but their therapeutic efficacy is limited by insufficient immune modulation.Thus,the strategies achieving both immunomodulation and active myelin regeneration are highly desired.Here,we investigated a combination therapy(CT)for MS designed to simultaneously modulate immune responses and promote oligodendrocyte precursor cell differentiation and in situ remyelination in an experimental autoimmune encephalomyelitis mouse model.Remarkably,CT suppressed acute inflammatory activity,activated the signaling pathways for myelin development,induced the expression of myelin-related genes,and significantly promoted remyelination and the recovery of motor performance.Furthermore,a reduced immunomodulator dosage or shorter treatment duration with small-molecule drugs achieved comparable symptom reversal.Our findings demonstrate the potential of CT to address complex pathobiology and lay a foundation for developing novel therapeutic strategies for MS.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
文摘Background： Neuromyelitis optica spectrum disorder （NMOSD） was long believed to be an aggressive form of multiple sclerosis （MS）. This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice. Methods： Data including the patients＇ serum and cerebrospinal fluid （CSF） tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein （MOG） autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody （AQP4-Ab）. The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was peribrmed to analyze the continuous variables. Results： Totally 85 MS patients （49%） and 90 NMOSD patients （51%） were enrolled, including 124 （71%） women and 51 （29%） men. Fewer MS patients （6%） had autoinamune diseases compared to NMOSD （19%） （x2= 6.9, P 〈 0.01 ）. Patients with NMOSD had higher Expanded Disability Status Scale scores （3.5 [3]） than MS group （2 [2]） （x2= -3.69, P 〈 0.01）. The CSF levels of white cell count and protein in both two groups were slightly elevated titan the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients （MS： 0, NMOSD： 67%; x2= 63.9, P 〈 0.01 ）. Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS （MS： 59%, NMOSD： 20%; x2= 25.7, P 〈 0.01）. No significant difference of MOG autoantibodies was found between the two groups. Conclusion： The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.
文摘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.
文摘Background The incentives and the factors that affect the onset and outcome of optic neuritis （ON） are not very clear. The aim of this study is to define and get a comprehensive understanding of the clinical profile of ON, and to identify the factors that were related to the prognosis of the patients. Methods Medical records of patients with diagnosis of ON at Huashan Hospital, Fudan University between March 2008 and June 2011 were reviewed. Clinical features, ophthalmologic and neurologic assessments, neuroimaging studies, laboratory examinations, visual recovery, and final outcome of the patients were evaluated by the authors. Results Records of 50 patients （32 females and 18 males）, aged 15-56 years, were reviewed, in which 22% patients had a previous onset of ON. Maximal visual deficit was severe in 72.5% （〈20/200）. Abnormal rates of hormone levels and rheumatoid indicators were found in 54.2% and 25.0%. ANA test returned positive in 40%, oligoclonal banding （OCB） was identified in 31.3%, and Serum neuromyelitis optica （NMO）-IgG studies were abnormal in 25% of the patients. Neuroimaging abnormalities associated with ON were documented in six patients. Three of the 50 patients have been diagnosed with multiple sclerosis, and two with NMO. Visual acuity was 20/20 or better in 26.1% and 20/100 or worse in 39.1% affected eyes at the last visit. Poor visual acuity at onset is the main factor that would affect the final outcome of vision （P 〈0.05）. Conclusions Vision defects of this group of patients were severe. Females had a higher incidence of ON than males. Hormone levels, rheumatoid indicators and immune parameters may be related to the onset of ON. The severe reduction of visual acuity at onset may be related to the poor outcome of vision in ON patients.
