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.

Imaging and clinical properties of inflammatory demyelinating pseudotumor in the spinal cord

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.

New insights into the immunologic role of oligodendrocyte lineage cells in demyelination diseases

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.

An improved fiber tracking algorithm based on fiber assignment using the continuous tracking algorithm and two-tensor model

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.

Sudden blindness in a child with Crohn's disease

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.

Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family

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.

Comparative Analysis of Post-Rehabilitation Neuropsychological Profile of a Patient with Susac Syndrome—A Case Report

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.

Clinical and pathological features of acute optic neuritis in Chinese patients

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.

Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

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.

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.